FN Thomson Reuters Web of Science™ VR 1.0 PT J AU FRENZ, DA LIU, W WILLIAMS, JD HATCHER, V GALINOVICSCHWARTZ, V FLANDERS, KC VANDEWATER, TR AF FRENZ, DA LIU, W WILLIAMS, JD HATCHER, V GALINOVICSCHWARTZ, V FLANDERS, KC VANDEWATER, TR TI INDUCTION OF CHONDROGENESIS - REQUIREMENT FOR SYNERGISTIC INTERACTION OF BASIC FIBROBLAST GROWTH-FACTOR AND TRANSFORMING GROWTH-FACTOR-BETA SO DEVELOPMENT LA English DT Article DE CHONDROGENESIS; EPITHELIAL-MESENCHYMAL INTERACTIONS; BFGF; TGF-BETA-1 ID CAPILLARY ENDOTHELIAL-CELLS; TGF-BETA; DIFFERENTIATED CHONDROCYTES; MESENCHYMAL CONDENSATION; EXTRACELLULAR-MATRIX; EXPRESSION PATTERN; COLONY FORMATION; GENE-EXPRESSION; SOFT AGAR; TGF-BETA-1 AB Interactions between the epithelial anlage of the developing mouse inner ear and its associated periotic mesenchyme control the differentiation of the cartilaginous otic capsule. Transforming growth factor-beta(1) (TGF-beta(1)) is a naturally occurring signal peptide that is present in these tissues at times of active differentiation and morphogenesis. Previous studies have shown that TGF-beta(1) alone is not a sufficient stimulus to initiate chondrogenesis in cultured periotic mesenchyme. In this study, we provide evidence that basic fibroblast growth factor (bFGF) can elicit a specific but limited chondrogenic response in cultured periotic mesenchymal cells. We also demonstrate that simultaneous addition of bFGF and TGF-beta(1) to cultured periotic mesenchyme results in a full chondrogenic response comparable to that which occurs when periotic mesenchyme is grown in the presence of its natural inductor tissue (i.e. otic epithelium). Utilizing antibodies directed against bFGF, we show localization of endogenous bFGF in the otic epithelium in vivo and in mixed epithelial-mesenchymal cultures. Additionally, we demonstrate the presence of FGF-like activity in medium conditioned by otic epithelium. Blocking of epithelial elicited chondrogenesis by a combination of both alpha bFGF and alpha TGF-beta(1) antibodies provides further evidence of the necessity for these growth factors in the chondrogenic differentiation of periotic mesenchyme in vitro. Our results suggest a role for both bFGF and TGF-beta(1) in the regulation of chondrogenesis during otic capsule formation in situ. C1 ALBERT EINSTEIN COLL MED,DEPT ANAT & STRUCT BIOL,BRONX,NY 10461. ALBERT EINSTEIN COLL MED,DEPT NEUROSCI,BRONX,NY 10461. ALBERT EINSTEIN COLL MED,DEPT BIOCHEM,BRONX,NY 10461. ALBERT EINSTEIN COLL MED,DEPT MED,BRONX,NY 10461. NATL CANC INST,CHEMOPREVENT LAB,BETHESDA,MD 20892. RP FRENZ, DA (reprint author), ALBERT EINSTEIN COLL MED,DEPT OTOLARYNGOL,BRONX,NY 10461, USA. FU NIDCD NIH HHS [NIDCD DC-00081, NIDCD DC-00088]; NINDS NIH HHS [NIND NS-07098] NR 55 TC 92 Z9 100 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD FEB PY 1994 VL 120 IS 2 BP 415 EP 424 PG 10 WC Developmental Biology SC Developmental Biology GA MW036 UT WOS:A1994MW03600017 PM 8149917 ER PT J AU MAENO, M ONG, RC XUE, Y NISHIMATSU, S UENO, N KUNG, HF AF MAENO, M ONG, RC XUE, Y NISHIMATSU, S UENO, N KUNG, HF TI REGULATION OF PRIMARY ERYTHROPOIESIS IN THE VENTRAL MESODERM OF XENOPUS-GASTRULA EMBRYO - EVIDENCE FOR THE EXPRESSION OF A STIMULATORY FACTOR(S) IN ANIMAL POLE TISSUE SO DEVELOPMENTAL BIOLOGY LA English DT Article ID BONE MORPHOGENETIC PROTEIN-4; LAEVIS; INDUCTION C1 UNIV TSUKUBA,INST APPL BIOCHEM,TSUKUBA,IBARAKI 305,JAPAN. HOKKAIDO UNIV,FAC PHARMACEUT SCI,SAPPORO,HOKKAIDO 060,JAPAN. RP MAENO, M (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,FREDERICK,MD 21702, USA. RI Nishimatsu, Shin-ichiro/C-4188-2012; Ueno, Naoto/B-3307-2015 NR 19 TC 52 Z9 52 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD FEB PY 1994 VL 161 IS 2 BP 522 EP 529 DI 10.1006/dbio.1994.1050 PG 8 WC Developmental Biology SC Developmental Biology GA MV530 UT WOS:A1994MV53000017 PM 8313998 ER PT J AU WEST, JA SIVAK, JG PASTERNAK, J PIATIGORSKY, J AF WEST, JA SIVAK, JG PASTERNAK, J PIATIGORSKY, J TI IMMUNOLOCALIZATION OF S-CRYSTALLINS IN THE DEVELOPING SQUID (LOLIGO-OPALESCENS) LENS SO DEVELOPMENTAL DYNAMICS LA English DT Article DE CEPHALOPOD; LENS PROTEINS; DEVELOPMENT ID PHYSICOCHEMICAL CHARACTERIZATION; MESSENGER-RNA; FIBER CELLS; PROTEINS; RECRUITMENT; EVOLUTION; ENZYMES; CHICKEN AB S-crystallins are the predominant soluble proteins of the squid lens. Of these, S-III crystallin is the major component and S-I and S-II crystallin are the minor lens components. The lens has a posterior and anterior segment, each derived from separate groups of ectodermal cells referred to as lentigenic cells. In the present study, the appearance of S-crystallins during the development of the lens of Loligo opalescens was followed by immuno-cytochemistry. S-crystallins of the lens and lentigenic cells were first observed at day 17 (Arnold stage 27) of embryogenesis. S-crystallins were not confined to a single region, but were present in the middle group (group 2) of lentigenic cells, the posterior lens primordium, and the processes connecting the lentigenic cells and the posterior lens primordium. Two days later (Arnold stage 28), the S-crystallins were also observed in the anterior group (group 1) of lentigenic cells, the anterior lens primordium, and the processes connecting the cells with the anterior lens primordium. Thus, during development, S-crystallins accumulate first in the posterior lens primordium and subsequently in the anterior lens primordium and their respective lentigenic cells and connecting lentigenic processes. Incubated sections of the adult lens and lentigenic cells also show specific immuno-peroxidase staining when compared with controls. This evidence in combination with a recent investigation (West [1993] Ph.D. dissertation), which indicates that the cephalopod lens continues to grow throughout adulthood, suggests that squid lens crystallins are synthesized during adulthood. (C) 1994 Wiley-Liss, Inc. C1 UNIV WATERLOO,SCH OPTOMETRY,WATERLOO N2L 3G1,ON,CANADA. UNIV WATERLOO,DEPT BIOL,WATERLOO N2L 3G1,ON,CANADA. NEI,BETHESDA,MD 20892. NR 37 TC 7 Z9 7 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD FEB PY 1994 VL 199 IS 2 BP 85 EP 92 PG 8 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA MZ053 UT WOS:A1994MZ05300001 PM 8204909 ER PT J AU SPRAUL, M ANDERSON, EA BOGARDUS, C RAVUSSIN, E AF SPRAUL, M ANDERSON, EA BOGARDUS, C RAVUSSIN, E TI MUSCLE SYMPATHETIC-NERVE ACTIVITY IN RESPONSE TO GLUCOSE-INGESTION - IMPACT OF PLASMA-INSULIN AND BODY-FAT SO DIABETES LA English DT Article ID SKELETAL-MUSCLE; ENERGY-EXPENDITURE; MAJOR DETERMINANT; PIMA-INDIANS; NOREPINEPHRINE; HUMANS; RESISTANCE; OBESITY; SYSTEM; HYPERINSULINEMIA AB Carbohydrate intake stimulates sympathetic nervous system activity in lean subjects, whereas in obese subjects, the results have been inconsistent. The aim of this study was to directly measure sympathetic neural outflow to skeletal muscle in response to a 75-g oral glucose tolerance test (OGTT) in 15 Pima Indian and 16 Caucasian men, matched for body fat and age, but covering a large range of body weight (57-113 kg) and body fat (4-41%). Fasting muscle sympathetic nerve activity (MSNA) correlated positively with body fat (r = 0.73; P = 0.001) In Caucasians but not in Pima Indians, whereas the increase in MSNA during the OGTT correlated negatively with the percentage of body fat (r -0.38, P = 0.03) independently of race. In each subject, the increase in MSNA over time correlated positively with the increase in plasma insulin levels, but the slopes of these relationships were inversely related to the percentage of body fat (r= -0.52, P = 0.003) independently of race. In conclusion, obesity is associated with a higher fasting sympathetic neural outflow to muscle but a blunted increase in response to an oral glucose load despite a larger increase in plasma insulin levels. This blunted response may represent another feature of the obesity/insulin resistance syndrome. C1 NIDDKD,CLIN DIABET & NUTR SECT,PHOENIX,AZ. UNIV IOWA,COLL MED,DEPT ANESTHESIA,IOWA CITY,IA. UNIV IOWA,COLL MED,CTR CARDIOVASC,IOWA CITY,IA. RP SPRAUL, M (reprint author), UNIV DUSSELDORF,DEPT NUTR & METAB,POSTFACH 101007,MOORENSTR 5,D-40001 DUSSELDORF,GERMANY. FU NHLBI NIH HHS [HL-43514, HL-44546] NR 33 TC 62 Z9 65 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 1994 VL 43 IS 2 BP 191 EP 196 DI 10.2337/diabetes.43.2.191 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NG397 UT WOS:A1994NG39700004 PM 8288042 ER PT J AU CARO, LHP OHALI, A GORDEN, P COLLIER, E AF CARO, LHP OHALI, A GORDEN, P COLLIER, E TI MUTATIONAL ANALYSIS OF THE NH2-TERMINAL GLYCOSYLATION SITES OF THE INSULIN-RECEPTOR ALPHA-SUBUNIT SO DIABETES LA English DT Article ID N-LINKED OLIGOSACCHARIDE; VIRUS-G-PROTEIN; TYROSINE KINASE; BETA-SUBUNIT; 3T3-L1 ADIPOCYTES; CELL-SURFACE; TRANSPORT; BIOSYNTHESIS; MUTAGENESIS; EXPRESSION AB The insulin receptor is synthesized as a single chain of 190 kiloDaltons, which is processed to disulfide-linked mature alpha- and beta-subunits, containing N- and O-linked oligosaccharides and fatty acids. Previously (Collier E, Carpentier J-L, Beitz L, Caro LHP, Taylor SI, Gorden P: Biochemistry 32:7818-23, 1993), site directed mutagenesis of the asparagine in the first four sites of N-linked glycosylation to glutamine resulted in a receptor that was retained in the endoplasmic reticulum and not processed past the proreceptor form. In this study, mutation of these sites individually and in various combinations is studied. Mutation in the first or second glycosylation site does not significantly impair processing of the receptor; the receptor is found on the cell surface and binds insulin normally. If both the first and second sites are mutated, a significant reduction occurs in the amount of receptor found on the cell surface and in insulin binding. There is some processing of the receptor in cells expressing this mutant compared with the four-part mutant. If only the third and fourth sites are mutated, processing is impaired less than in the mutant with the first and second sites mutated. However, the amount of receptor found on the cell surface is less than in the mutant of only the first or only the second site. In all of these glycosylation mutants, the amount of receptor on the cell surface correlates with the level of I-125-labeled insulin binding on the cell surface. The receptors on the cell surface are able to autophosphorylate in response to insulin in proportion to the amount of binding found on the cell surface. N-linked glycosylation of the NH2-terksminal of the alpha-subunit of the insulin receptor is necessary for normal processing and cell surface expression of the insulin receptor but not for the function of the receptor. Specific sites of glycosylation and the number of sites glycosylated both determine the amount of receptor processed. C1 NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. NR 32 TC 17 Z9 17 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 1994 VL 43 IS 2 BP 240 EP 246 DI 10.2337/diabetes.43.2.240 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NG397 UT WOS:A1994NG39700011 PM 8288048 ER PT J AU ROBISON, WG AF ROBISON, WG TI ALDOSE REDUCTASE INHIBITION AND RETINOPATHY SO DIABETES LA English DT Letter ID RETINAL CAPILLARIES; PREVENTION; DOGS RP ROBISON, WG (reprint author), NEI,BLDG 6,ROOM 316,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 12 TC 5 Z9 5 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD FEB PY 1994 VL 43 IS 2 BP 337 EP 338 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NG397 UT WOS:A1994NG39700023 PM 8288059 ER PT J AU GREINER, JW GUADAGNI, F ROSELLI, M ULLMANN, CD NIERODA, C SCHLOM, J AF GREINER, JW GUADAGNI, F ROSELLI, M ULLMANN, CD NIERODA, C SCHLOM, J TI IMPROVED EXPERIMENTAL RADIOIMMUNOTHERAPY OF COLON XENOGRAFTS BY COMBINING I-132 CC49 AND INTERFERON-GAMMA SO DISEASES OF THE COLON & RECTUM LA English DT Article; Proceedings Paper CT 3rd International Workshop on Colorectal Cancer: Biological and Surgical Relationships CY MAR 03-04, 1994 CL ROME, ITALY DE INTERFERON-GAMMA; RADIOIMMUNOTHERAPY; ANTITUMOR-ASSOCIATED GLYCOPROTEIN-72 MONOCLONAL ANTIBODY; ANTIGEN AUGMENTATION ID CARCINOEMBRYONIC ANTIGEN EXPRESSION; TUMOR-ASSOCIATED GLYCOPROTEIN-72; MONOCLONAL-ANTIBODIES; CELLS; CARCINOMA; ENHANCEMENT; PHARMACOKINETICS; SPECTRUM; MELANOMA; FAMILY AB PURPOSE: This study was designed to determine whether the ability of interferon-gamma to upregulate the expression of a human tumor antigen improved the therapeutic efficacy of a radionuclide-conjugated monoclonal antibody. METHODS: Tumor xenografts of the moderately differentiated human colon tumor cell line HT-29 were grown in athymic mice. Constitutive levels of the human tumor antigen, tumor-associated glycoprotein-72, were measured before and after treatment with interferon-gamma. Antitumor effects of an I-131-labeled antitumor-associated glycoprotein-72 monoclonal antibody, CC49, were determined by measuring changes in tumor volumes in the respective groups of athymic mice. RESULTS: Interferon-gamma induced a time-dependent and dose-dependent increase in tumor-associated glycoprotein-72 expression in the HT-29 tumors. Immunohistochemical staining revealed a more homogeneous tumor-associated glycoprotein-72-positive tumor cell population in tumors isolated from mice treated for eight days with interferon-gamma, which accounted for the enhanced tumor localization of I-131-CC49 in mice. That experimental model was used to examine the antitumor effects of combining interferon-gamma with I-131-CC49. Administration of 300 mu Ci of I-131-CC49 to mice bearing HT-29 tumors induced a transient suppression of tumor growth. Conversely, a long-term, sustained HT-29 tumor growth suppression was achieved in mice given 300 mu Ci Of I-131-CC49 and interferon-gamma. In fact, the cytokine/radioimmunoconjugate combination eradicated any evidence of tumor in approximately 30 percent of the mice. CONCLUSION: The ability of interferon-gamma to enhance tumor-associated glycoprotein-72 expression substantially augmented the antitumor effects of the radioimmunoconjugate. Those observations provide additional argument for use of a radioimmunoconjugate in combination with a cytokine to improve tumor diagnosis and therapy. C1 UNIV ROMA TOR VERGATA,SCH MED,REGINA ELENA CANC INST,CLIN PATHOL LAB,ROME,ITALY. UNIV ROMA TOR VERGATA,SCH MED,DEPT SURG,ROME,ITALY. RP GREINER, JW (reprint author), NCI,TUMOR IMMUNOL & BIOL LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Guadagni, Fiorella/J-4432-2013 OI Guadagni, Fiorella/0000-0003-3652-0457 NR 24 TC 7 Z9 7 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0012-3706 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD FEB PY 1994 VL 37 IS 2 SU S BP S100 EP S105 DI 10.1007/BF02048441 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA MY711 UT WOS:A1994MY71100018 PM 8313780 ER PT J AU GUADAGNI, F ROSELLI, M COSIMELLI, M SPILA, A CAVALIERE, F ARCURI, R ABBOLITO, MR GREINER, JW SCHLOM, J AF GUADAGNI, F ROSELLI, M COSIMELLI, M SPILA, A CAVALIERE, F ARCURI, R ABBOLITO, MR GREINER, JW SCHLOM, J TI BIOLOGIC EVALUATION OF TUMOR-ASSOCIATED GLYCOPROTEIN-72 AND CARCINOEMBRYONIC ANTIGEN EXPRESSION IN COLORECTAL-CANCER .1. SO DISEASES OF THE COLON & RECTUM LA English DT Article; Proceedings Paper CT 3rd International Workshop on Colorectal Cancer: Biological and Surgical Relationships CY MAR 03-04, 1994 CL ROME, ITALY DE TUMOR ANTIGEN; MONOCLONAL ANTIBODY; COLORECTAL CARCINOMA; SERUM MARKER; ANTIGEN PHENOTYPE ID MONOCLONAL-ANTIBODY B72.3; TAG-72; CARCINOMA; COLON; REACTIVITY; SERUM; CEA; ADENOCARCINOMAS; GENERATION; DIAGNOSIS AB Tumor-associated glycoprotein-72 has been recently suggested as a new serum marker for colorectal cancer. In fact, approximately 40 percent of colorectal cancer patients have positive tumor-associated glycoprotein-72 serum levels at the time of diagnosis, while only 3 percent of patients with benign diseases are positive. A longitudinal evaluation of colorectal cancer patients suggested the utility of combining the measurement of tumor-associated glycoprotein-72 with that of carcinoembryonic antigen to monitor disease status not only at the time of diagnosis, but also at the time of recurrence. Several reports have indicated that the expression of some tumor antigens in colorectal adenomas may correlate with those parameters conventionally considered as indicative of malignant transformation. The presence of tumor-associated glycoprotein-72 in colorectal adenomas has been recently correlated with preneoplastic lesions, suggesting that tumor-associated glycoprotein-72 may be considered as an early marker of neoplastic transformation. The evaluation of tumor antigens can be considered a new tool in the management of colorectal cancer. C1 UNIV ROMA TOR VERGATA,DEPT SURG,ROME,ITALY. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. RP GUADAGNI, F (reprint author), REGINA ELENA INST CANC RES,VIALE REGINA ELENA 291,I-00161 ROME,ITALY. RI Guadagni, Fiorella/J-4432-2013; Cavaliere, Francesco/J-7635-2016 OI Guadagni, Fiorella/0000-0003-3652-0457; Cavaliere, Francesco/0000-0001-6501-8648 NR 34 TC 4 Z9 4 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0012-3706 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD FEB PY 1994 VL 37 IS 2 SU S BP S16 EP S23 DI 10.1007/BF02048426 PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA MY711 UT WOS:A1994MY71100003 PM 8313787 ER PT J AU MANNIRONI, C ORR, A HATCH, C PILCH, D IVANOVA, V BONNER, W AF MANNIRONI, C ORR, A HATCH, C PILCH, D IVANOVA, V BONNER, W TI THE RELATIVE EXPRESSION OF HUMAN HISTONE H2A GENES IS SIMILAR IN DIFFERENT TYPES OF PROLIFERATING CELLS SO DNA AND CELL BIOLOGY LA English DT Article ID MESSENGER-RNA DEGRADATION; PROTEIN-SYNTHESIS; DNA-REPLICATION; TRANSCRIPTION; INHIBITION; SEQUENCE; CORE; POLYADENYLATION; ISOPROTEIN; OOCYTES AB To help elucidate the factors regulating the expression of histone multigene families in proliferating cells, we asked whether the relative expression of different members of such a family was dependent upon or independent of the type of proliferating cell. This question was examined by measuring the relative expression of seven members of the human histone H2A multigene family in four cell lines of diverse origin. Two previously uncharacterized members of the H2A gene family were found to be the most abundantly expressed of the seven in all four cell lines. One of these encodes an H2A.2 species containing methionine. The lines examined in the study were Jurkat (a lymphoma line), N-tera (a pluripotent embryonic carcinoma line), HeLa (originally isolated as a cervical carcinoma), and IMR90 (a normal embryonic fibroblastic line). The amount of each mRNA species was quantitated using oligonucleotides about 30 bases long complementary to the 5' or 3' untranslated regions. In each cell line, there was at least an eight-fold difference in the amount of the most and least highly expressed of the seven H2A mRNA species. In addition, there were up to five-fold differences among the cell lines in the amount of the H2A mRNA species as a fraction of total RNA. However, in contrast to those differences, the four cell lines were found to express the seven H2A mRNAs in similar relative amounts. These findings suggest that the relative expression of the individual members of a histone gene family is independent of the type of replicating cell. C1 NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,DEV THERAPEUT DEV,BLDG 37,ROOM 5D17,BETHESDA,MD 20892. RI mannironi, cecilia/I-3542-2013 NR 38 TC 12 Z9 14 U1 1 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD FEB PY 1994 VL 13 IS 2 BP 161 EP 170 DI 10.1089/dna.1994.13.161 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA NC858 UT WOS:A1994NC85800006 PM 8179821 ER PT J AU PASCUALLEONE, A COHEN, LG BRASILNETO, JP HALLETT, M AF PASCUALLEONE, A COHEN, LG BRASILNETO, JP HALLETT, M TI NONINVASIVE DIFFERENTIATION OF MOTOR CORTICAL REPRESENTATION OF HAND MUSCLES BY MAPPING OF OPTIMAL CURRENT DIRECTIONS SO ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE MOTOR CORTEX; TRANSCRANIAL MAGNETIC STIMULATION; CURRENT DIRECTION, VECTOR; PHYSIOLOGY; ELECTROMYOGRAPHY (EMG); (HUMAN) ID FOCAL MAGNETIC STIMULATOR; HUMAN-BRAIN; CORTEX; COIL; ACTIVATION; DISTRIBUTIONS; ORIENTATION; RESPONSES AB Non-invasive mapping of human motor cortex by stimulating different scalp positions with a magnetic coil held at a constant orientation allows differentiation of proximal and distal arm muscles. This study describes a technique for more precise mapping of closely represented muscles using different orientations of a coil that delivers nearly monopolar current pulses. EMG was recorded from abductor pollicis brevis (APB), first dorsal interosseous (FDI), abductor digiti minimi (ADM), and flexor carpi radialis (FCR) of 9 normal volunteers. Stimuli were delivered from a Dantec stimulator through an 8-shaped coil. The center of the coil was kept nat on the scalp on a given position, and the coil rotated at different angles. The amplitudes of the motor evoked potentials were used for calculation of optimal current directions in the brain for activation of each muscle in each position. The optimal current direction for FCR activation pointed antero-medially. ADM, FDI and APB mapped progressively more antero-laterally. The relationship between current directions was constant across subjects and did not change in different scalp positions. This technique improves the spatial resolution of non-invasive cortical mapping and may express the differences in orientations of interneuronal nets in the precentral gyrus. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,HUMAN CORT CONTROL SECT,BETHESDA,MD 20892. RI Brasil-Neto, Joaquim/A-1171-2009 NR 33 TC 61 Z9 62 U1 1 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0013-4694 J9 ELECTROEN CLIN NEURO JI Electroencephalogr. Clin. Neurophysiol. PD FEB PY 1994 VL 93 IS 1 BP 42 EP 48 DI 10.1016/0168-5597(94)90090-6 PG 7 WC Engineering, Biomedical; Clinical Neurology SC Engineering; Neurosciences & Neurology GA MZ898 UT WOS:A1994MZ89800007 PM 7511521 ER PT J AU ROTH, BJ MACCABEE, PJ EBERLE, LP AMASSIAN, VE HALLETT, M CADWELL, J ANSELMI, GD TATARIAN, GT AF ROTH, BJ MACCABEE, PJ EBERLE, LP AMASSIAN, VE HALLETT, M CADWELL, J ANSELMI, GD TATARIAN, GT TI IN-VITRO EVALUATION OF A 4-LEAF COIL DESIGN FOR MAGNETIC STIMULATION OF PERIPHERAL-NERVE SO ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE MAGNETIC STIMULATION; COIL; PERIPHERAL NERVE ID FIELDS; FIBER AB The performance of a 4-leaf magnetic coil was evaluated during magnetic stimulation of a peripheral nerve in vitro. The site of stimulation was below the coil center, and a 90 degrees rotation of the coil was equivalent to a change in current polarity. A hyperpolarizing magnetic stimulus failed to slow or block a propagating action potential. C1 SUNY HLTH SCI CTR,DEPT NEUROL,BROOKLYN,NY. SUNY HLTH SCI CTR,DEPT PHYSIOL,BROOKLYN,NY. NINCDS,BETHESDA,MD. CADWELL LABS INC,KENNEWICK,WA. RP ROTH, BJ (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BLDG 13,ROOM 3W13,BETHESDA,MD 20892, USA. RI Roth, Bradley/A-4920-2008 NR 14 TC 33 Z9 34 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0013-4694 J9 ELECTROEN CLIN NEURO JI Electroencephalogr. Clin. Neurophysiol. PD FEB PY 1994 VL 93 IS 1 BP 68 EP 74 DI 10.1016/0168-5597(94)90093-0 PG 7 WC Engineering, Biomedical; Clinical Neurology SC Engineering; Neurosciences & Neurology GA MZ898 UT WOS:A1994MZ89800010 PM 7511524 ER PT J AU WEINMANN, W PARKER, CE BAUMEISTER, K MAIER, C TOMER, KB PRZYBYLSKI, M AF WEINMANN, W PARKER, CE BAUMEISTER, K MAIER, C TOMER, KB PRZYBYLSKI, M TI CAPILLARY ELECTROPHORESIS COMBINED WITH CF-252 PLASMA DESORPTION AND ELECTROSPRAY MASS-SPECTROMETRY FOR THE STRUCTURAL CHARACTERIZATION OF HYDROPHOBIC POLYPEPTIDES USING ORGANIC-SOLVENTS SO ELECTROPHORESIS LA English DT Article ID FATTY ACYLATION; PROTEINS; PEPTIDES; PALMITOYLATION; OPTIMIZATION AB Capillary electrophoresis (CE) conditions have been developed for the separation of hydrophobic polypeptides, such as fatty acid-acylated peptides, and their subsequent structural identification by Cf-252 plasma desorption (PDMS) and electrospray mass spectrometry (ESMS). Salt- and detergent-free aqueous acetic acid buffers containing up to 20% 2-propanol or 25% acetonitrile were employed for CE separations of hydrophobic peptides with (i) untreated, and (ii) 3-aminopropyltrimethoxysilane-derivatized fused silica capillaries. For both capillary types, electroosmotic flow rates suitable for sample isolation and transfer were determined, and CE separations of polypeptide mixtures were compared for aqueous buffers containing 2-propanol or acetonitrile. For the mass spectrometric identification of CE-separated peptides, a sheath flow sample isolation method was developed for subsequent transfer to PDMS. This procedure enabled the efficient isolation of peptide fractions for PDMS analysis, or alternative microanalytical techniques.* C1 UNIV KONSTANZ,FAK CHEM,D-78434 CONSTANCE,GERMANY. NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. RI Tomer, Kenneth/E-8018-2013 NR 17 TC 18 Z9 18 U1 0 U2 2 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 FEB PY 1994 VL 15 IS 2 BP 228 EP 233 DI 10.1002/elps.1150150139 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA NB525 UT WOS:A1994NB52500020 PM 8026439 ER PT J AU KOONIN, EV BORK, P SANDER, C AF KOONIN, EV BORK, P SANDER, C TI YEAST CHROMOSOME-III - NEW GENE FUNCTIONS SO EMBO JOURNAL LA English DT Article DE COMPUTER METHODS; GENOME ANALYSIS; PREDICTION OF PROTEIN FUNCTION; PREDICTION OF PROTEIN STRUCTURE; PROTEIN SEQUENCE ANALYSIS ID SACCHAROMYCES-CEREVISIAE; NUCLEOTIDE-SEQUENCE; ESCHERICHIA-COLI; PROTEINS; ALIGNMENT; MEMBRANE; REPLICATION; CLONING AB One year after the release of the sequence of yeast chromosome III, we have re-examined its open reading frames (ORFs) by computer methods. More than 61% of the 171 probable gene products have significant sequence similarities in the current databases; as many as 54% have already known functions or are related to functionally characterized proteins, allowing partial prediction of protein function, 11 percentage points more than reported a year ago; 19% are similar to proteins of known three-dimensional structure, allowing model building by homology. The most interesting new identifications include a sugar kinase distantly related to ribokinases, a phosphatidyl serine synthetase, a putative transcription regulator, a flavodoxin-like protein, and a zinc finger protein belonging to a distinct subfamily. Several ORFs have similarities to uncharacterized proteins, resulting in new families 'in search of a function'. About 54% of ORFs match sequences from other phyla, including numerous fragments in the database of expressed sequence tags (ESTs). Most significant similarities to ESTs are with proteins in conserved families widely represented in the databases. About 30% of ORFs contain one or more predicted transmembrane segments. The increase in the power of functional and structural prediction comes from improvements in sequence analysis and from richer databases and is expected to facilitate substantially the experimental effort in characterizing the function of new gene products. C1 EUROPEAN MOLEC BIOL LAB, D-69012 HEIDELBERG, GERMANY. MAX DELBRUCK CTR MOLEC MED, D-13125 BERLIN, GERMANY. RP NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20894 USA. RI sander, chris/H-1452-2011; Bork, Peer/F-1813-2013 OI Bork, Peer/0000-0002-2627-833X NR 58 TC 91 Z9 99 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD FEB 1 PY 1994 VL 13 IS 3 BP 493 EP 503 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV864 UT WOS:A1994MV86400001 PM 8313894 ER PT J AU LOH, YP KON, OL PU, LP AF LOH, YP KON, OL PU, LP TI INCREASE IN DESACETYL-ALPHA-MSH CELLS IN RAT ANTERIOR-PITUITARY FOLLOWING ADRENAL ENUCLEATION AND ADRENALECTOMY SO ENDOCRINE LA English DT Article ID MELANOCYTE-STIMULATING HORMONE; OPIOMELANOCORTIN CONVERTING ENZYME; INTERMEDIATE LOBE; PRO-OPIOMELANOCORTIN; PEPTIDES; PROTEASE; GLAND; KEX2; PROOPIOMELANOCORTIN; IDENTIFICATION AB Radioimmunoassay and immunocytochemistry were used to investigate the cellular localization of the changes in processing of pro-opiomelanocortin (POMC) to immunoreactive (IR) alpha-MSH and IR-gamma(3)-MSH in the anterior pituitary of sham-operated, adrenalectomized and adrenal enucleated rats. Fourteen days after adrenalectomy, IR-alpha-MSH and IR-gamma(3)-MSH in anterior pituitary increased 2.1 and 1.8 fold respectively, relative to sham-operated rats. Similarly, IR-alpha-MSH and IR-gamma(3)-MSH increased 3.1 and 2.1 ford respectively, fourteen days after adrenal enucleation. IR-alpha-MSH and IR-gamma(3)-MSH were increased in approximately equimolar amounts with both surgical operations. Immunocytochemistry using two antisera to alpha-MSH which distinguish authentic alpha-MSH from the desacetyl form identified the alpha-MSH in anterior pituitary to be in the desacetyl form. Immunoreactive desacetyl alpha-MSH was localized to a subpopulation of corticotrophs which increased in numbers after adrenalectomy or adrenal enucleation. The ratio of IR-alpha-MSH content/number of alpha-MSH immunopositive cells was constant between sham-operated, adrenalectomized and adrenal enucleated animals. We propose that this increase of desacetyl alpha-MSH expressing cells is the result of either an induction of the ACTH cleaving enzyme(s) in a larger number of corticotrophs synthesizing alpha-MSH, or de novo generation of more alpha-MSH expressing cells by cell proliferation in the anterior pituitary, following adrenal surgery. RP LOH, YP (reprint author), NICHHD,DEV NEUROBIOL LAB,CELLULAR NEUROBIOL SECT,BETHESDA,MD 20892, USA. NR 42 TC 2 Z9 2 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0969-711X J9 ENDOCRINE JI Endocrine PD FEB PY 1994 VL 2 IS 2 BP 115 EP 121 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PL770 UT WOS:A1994PL77000005 ER PT J AU HAMMOND, GL SMITH, CL LAHTEENMAKI, P GROLLA, A WARMELSRODENHISER, S HODGERT, H MURAI, JT SIITERI, PK AF HAMMOND, GL SMITH, CL LAHTEENMAKI, P GROLLA, A WARMELSRODENHISER, S HODGERT, H MURAI, JT SIITERI, PK TI SQUIRREL-MONKEY CORTICOSTEROID-BINDING GLOBULIN - PRIMARY STRUCTURE AND COMPARISON WITH THE HUMAN PROTEIN SO ENDOCRINOLOGY LA English DT Article ID HUMAN TRANSCORTIN; CORTISOL; AFFINITY; SERUM; SITE; RNA; NITROCELLULOSE; PURIFICATION; SUBSTITUTION; INHIBITORS AB Squirrel monkey (Saimiri sciureus) corticosteroid-binding globulin (CBG) is the product of a 1.6-kilobase mRNA in the liver. Analyses of two overlapping cDNAs revealed that the squirrel monkey CBC precursor comprises 406 amino acids, the first 22 residues of which exhibit 91% identity with the human CBG leader sequence. The mature form of squirrel monkey CBG, therefore, very likely comprises 384 amino acids and has a polypeptide mol wt of 42,854. Compared to human CBG, the squirrel monkey protein contains an additional residue (threonine) at position 144, and the two proteins exhibit 86% sequence identity if this is taken into account. Squirrel monkey CBG contains five consensus sites for N-glycosylation, four of which are located in analogous positions in human CBG, and has two cysteine residues in the same relative positions as the cysteines in human CBG. Unlike CBG in most other species, squirrel monkey CBG appears to circulate as a dimer, and its affinity for glucocorticoids is remarkably low. We, therefore, expressed cDNAs for human and squirrel monkey CBGs in Chinese hamster ovary (CHO) cells and compared the physico-chemical properties of the products with those of the corresponding serum proteins. Squirrel monkey CBG is produced by CHO cells as a dimer, and its subunit size heterogeneity is similar to that associated with CBG in serum. In addition, the cortisol-binding affinity of squirrel monkey CBG produced by CHO cells is similar to that of the natural protein and is 5- to 8-fold lower than that of natural or recombinant human CBG. Mutants in which a threonine at position 144 was either added to human CBG or subtracted from squirrel monkey CBG were also expressed in CHO cells. This demonstrated that this additional amino acid in the squirrel monkey CBG sequence may actively contribute to its propensity for spontaneous dimerization, but does not account for its relatively low steroid-binding affinity. C1 UNIV WESTERN ONTARIO, DEPT OBSTET & GYNECOL, LONDON N6A 4L6, ON, CANADA. UNIV WESTERN ONTARIO, DEPT BIOCHEM, LONDON N6A 4L6, ON, CANADA. UNIV WESTERN ONTARIO, DEPT ONCOL, LONDON N6A 4L6, ON, CANADA. UNIV WESTERN ONTARIO, MRC, FETAL & NEONATAL HLTH & DEV GRP, LONDON N6A 4L6, ON, CANADA. STEROID RES LAB, DEPT MED CHEM, HELSINKI, FINLAND. UNIV CALIF SAN FRANCISCO, SCH MED, DEPT OBSTET & GYNECOL, SAN FRANCISCO, CA 94143 USA. NCI, ENVIRONM EPIDEMIOL BRANCH, ROCKVILLE, MD 20892 USA. NR 41 TC 12 Z9 13 U1 1 U2 3 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 FEB PY 1994 VL 134 IS 2 BP 891 EP 898 DI 10.1210/en.134.2.891 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MV443 UT WOS:A1994MV44300052 PM 8299584 ER PT J AU RODBELL, M AF RODBELL, M TI BIOINFORMATICS - AN EMERGING MEANS OF ASSESSING ENVIRONMENTAL-HEALTH SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material RP RODBELL, M (reprint author), NATL INST ENVIRONM HLTH SCI,RES TRIANGLE PK,NC, USA. NR 0 TC 1 Z9 1 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 FEB PY 1994 VL 102 IS 2 BP 136 EP 136 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA NC418 UT WOS:A1994NC41800001 PM 8033831 ER PT J AU ADAMSON, RH TAKAYAMA, S SUGIMURA, T THORGEIRSSON, UP AF ADAMSON, RH TAKAYAMA, S SUGIMURA, T THORGEIRSSON, UP TI INDUCTION OF HEPATOCELLULAR-CARCINOMA IN NONHUMAN-PRIMATES BY THE FOOD MUTAGEN 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE; HEPATOCELLULAR CARCINOMA; HETEROCYCLIC AMINES; NONHUMAN PRIMATES ID BROILED SARDINE; BEEF EXTRACT; COOKED FOOD; CARCINOGENICITY; RATS; COMPOUND AB The heterocyclic aromatic amine 2-amino-3-methylimidazo [4,5-f] quinoline (IQ) was evaluated for carcinogenic effects in macaques, primarily cynomolgus monkeys. IQ was administered by gavage five times a week at doses of 10 or 20 mg/kg. IQ induced hepatocellular carcinoma in 55% of the animals at the low dose and in 95% of the animals at 20 mg/kg. The average latent period at the high dose level was 43 months and that at the low dose was 60 months. Generally, the tumor nodules exhibited a well-to moderately well-differentiated hepatocellular carcinoma, and a trabecular pattern was most frequently seen. Pulmonary metastases was also found in several of the monkeys. Thus, IQ is a potent carcinogen in nonhuman primates and is a potential carcinogen for humans. C1 NATL CANC CTR,RES INST,TOKYO 104,JAPAN. RP ADAMSON, RH (reprint author), NCI,DIV CANC ETIOL,BLDG 31,ROOM 11A03,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CP-51013] NR 12 TC 29 Z9 30 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 FEB PY 1994 VL 102 IS 2 BP 190 EP 193 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA NC418 UT WOS:A1994NC41800014 PM 8033850 ER PT J AU THORGEIRSSON, UP FARB, A VIRMANI, R ADAMSON, RH AF THORGEIRSSON, UP FARB, A VIRMANI, R ADAMSON, RH TI CARDIAC DAMAGE-INDUCED BY 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE IN NONHUMAN-PRIMATES SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE; CYTOTOXICITY; HETEROCYCLIC AMINES; MONKEYS; MYOCARDIUM ID ENDOMYOCARDIAL BIOPSY; BEEF EXTRACT; HETEROCYCLIC AMINES; BROILED SARDINE; DNA DAMAGE; CARCINOGENICITY; CARDIOMYOPATHY; CARDIOTOXICITY; ADRIAMYCIN; MUTAGENICITY AB The heterocyclic aromatic amine 2-amino-3-methylimidazo [4,5-f] quinoline (IQ) is a potent hepatocarcinogen in cynomologus and rhesus monkeys. The finding of high cardiac IQ-DNA adduct levels prompted a histopathological study of perfusion-fixed hearts from 10 tumor-bearing monkeys chronically dosed with IQ at 10 mg/kg or 20 mg/kg 5 days per week for 48-80 months. Two monkeys dosed only with the vehicle for IQ hydroxypropylcellulose, served as controls. All the monkeys had normal heart weights, and no abnormalities were observed upon gross inspection of the hearts. Microscopically, focal myocardial lesions were observed in 8 of 10 monkeys dosed with IQ. Light microscopic abnormalities included myocyte necrosis with or without chronic inflammatory infiltrates, interstitial fibrosis with myocyte hypertrophy or atrophy, and vasculitis. Electron microscopic findings included disruption of the mitochondrial architecture (i.e., mitochondrial swelling and clearing of matrix densities), myofibrillar loss, disorganization of the normal alignment of sarcomeres, and occasional myocytes showing nuclear hypertrophy of peripheral clumping of the nuclear chromatin. There was some correlation between the cumulative dose of IQ and the extent of the myocardial abnormalities. These findings suggest that chronic exposure to IQ can lead to myocardial damage in monkeys. Although focal and not associated with clinincal evidence of heart failure, these abnormalities may represent the initial stages of IQ-induced toxic cardiomyopathy. C1 NCI,DIV CANC ETIOL,BETHESDA,MD 20892. ARMED FORCES INST PATHOL,WASHINGTON,DC 20306. FU NCI NIH HHS [N01-CP-51013] NR 38 TC 15 Z9 15 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 FEB PY 1994 VL 102 IS 2 BP 194 EP 199 DI 10.2307/3431611 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA NC418 UT WOS:A1994NC41800015 PM 8033851 ER PT J AU JOUNAIDI, Y BONFILS, C PERIN, F NEGISHI, M LANGE, R AF JOUNAIDI, Y BONFILS, C PERIN, F NEGISHI, M LANGE, R TI OVEREXPRESSION OF A CYTOCHROME-P-450 OF THE 2A FAMILY (CYP2A-5) IN CHEMICALLY-INDUCED HEPATOMAS FROM FEMALE MICE SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article ID MOUSE-LIVER TUMORS; COUMARIN 7-HYDROXYLASE; STEROID 15-ALPHA-HYDROXYLASE; MONOCLONAL-ANTIBODY; II P-45015-ALPHA; RAT-LIVER; EXPRESSION; HEPATOCARCINOGENESIS; MICROSOMES; PROTEINS AB Chemical hepatocarcinogenesis in female mice, induced by 5,9-dimethyl(7H)dibenzo[c,g] carbazole, leads to the overexpression of a cytochrome P-450 of the 2a family. This protein was identified as Cyp2a-5, by the use of immunoblots obtained from isoelectric focusing gels. This method allowed the distinction of Cyp2a-5 from Cyp2a-4, another mouse liver cytochrome P-450, by taking advantage of their slightly different pi values. The theoretical pi values, determined from the amino acid sequence, were pI 9.91 for Cyp2a-4 and pI 10.01 for Cyp2a-5. Other structurally related forms were not detected. In hepatomas from female mice, only the Cyp2a-5 form was overexpressed (2-3 fold). Male mice showed a weak expression of Cyp2a-4 and Cyp2a-5 in control liver samples and in hepatomas. The expression of both forms was increased more than fivefold upon castration. Pyrazole induces specifically the Cyp2a-5 form. The Cyp2a-5 overexpression was correlated with enhanced microsomal coumarin-7-hydroxylase and testosterone-15 alpha-hydroxylase activities. An immunohistochemical study showed that Cyp2a-4and Cyp2a-5 are expressed uniformly in female livers, but centrilobularly in male livers. In hepatomas, this localisation is perturbed; in females we observed a focal cell localisation, and the Cyp2a-containing cells were often hypertrophic and polyploid. In hepatomas from male mice, the Cyp2a-containing cells became dispersed. From a comparison with other studies, the Cyp2a-5 overexpression appears to be a general feature of hepatocarcinogenesis in mice. C1 INST CURIE,ORSAY,FRANCE. NIEHS,RES TRIANGLE PK,NC. RP JOUNAIDI, Y (reprint author), CNRS,INSERM,U128,BP 5051,ROUTE MENDE,F-34033 MONTPELLIER,FRANCE. NR 39 TC 24 Z9 24 U1 0 U2 0 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 FEB 1 PY 1994 VL 219 IS 3 BP 791 EP 798 DI 10.1111/j.1432-1033.1994.tb18559.x PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MW381 UT WOS:A1994MW38100010 PM 8112330 ER PT J AU RUBINEK, T LOYA, S SHAHARABANY, M HUGHES, SH CLARK, PK HIZI, A AF RUBINEK, T LOYA, S SHAHARABANY, M HUGHES, SH CLARK, PK HIZI, A TI THE CATALYTIC PROPERTIES OF THE REVERSE-TRANSCRIPTASE OF THE LENTIVIRUS EQUINE INFECTIOUS-ANEMIA VIRUS SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article ID DNA-POLYMERASE; ESCHERICHIA-COLI; MUTATIONAL ANALYSIS; CYSTEINE MUTATIONS; CRYSTAL-STRUCTURE; TYPE-1; MUTAGENESIS; INHIBITORS; DOMAIN; PURIFICATION AB The reverse transcriptase (RT) of equine infectious anemia virus (EIAV) shares sequence similarity with the RTs of other lentiviruses, particularly with the RTs of human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2, respectively), the causative agents of acquired immunodeficiency syndrome (AIDS). There is a 41-42% sequence identity between EIAV RT and both HIV RTs (which have 61% sequence identity to each other). We have compared the enzymic properties of EIAV RT with those of HIV-1 RT. Several aspects of the activities of EIAV RT differ from the corresponding activities of HIV-1 RT. There are significant differences in the inhibition of the DNA polymerase activities by the deoxynucleoside triphosphate analogs, 3'-azido-2,3'-dideoxythymidine triphosphate, dideoxyTTP and dideoxyGTP and by the nonnucleoside inhibitor, tetrahydroimidazo[4,5,1-jk-1,4]benzodiazepin-2-(1H)-one and thione; in the dependence of DNA polymerase and RNase H activities on pH; in the inhibition of the DNA polymerase activities by the thiol-specific reagent N-ethylmaleimide; in the specific DNA polymerase activity; in the inhibition of the ribonuclease H activity by the zinc chelator orthophenanthroline. However, there are several cases in which EIAV RT and KIV-1 RT are more similar than was previously found for HIV-1 RT and HIV-2 RT. These include the K, values for the DNA polymerase activities, the heat stability of the DNA polymerase functions and the specific activity of the RNase H function. C1 TEL AVIV UNIV,SACKLER SCH MED,DEPT CELL BIOL & HISTOL,IL-69978 TEL AVIV,ISRAEL. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,FREDERICK,MD. FU NCI NIH HHS [N01-CO-74101]; NIAID NIH HHS [AI-27035] NR 43 TC 10 Z9 10 U1 0 U2 0 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 FEB 1 PY 1994 VL 219 IS 3 BP 977 EP 983 DI 10.1111/j.1432-1033.1994.tb18580.x PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MW381 UT WOS:A1994MW38100031 PM 7509281 ER PT J AU ALBERTSON, BD HILL, RB SPRAGUE, KA WOOD, KE NIEMAN, LK LORIAUX, DL AF ALBERTSON, BD HILL, RB SPRAGUE, KA WOOD, KE NIEMAN, LK LORIAUX, DL TI EFFECT OF THE ANTIGLUCOCORTICOID RU486 ON ADRENAL STEROIDOGENIC ENZYME-ACTIVITY AND STEROIDOGENESIS SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID CUSHINGS-SYNDROME; ACTIVITY INVITRO; RU-486; PROGESTERONE; PLASMA; RADIOIMMUNOASSAY; KETOCONAZOLE; PITUITARY; CORTISOL; PRIMATES AB RU486, a synthetic steroid receptor antagonist, has strong antiprogesterone and antiglucocorticoid properties. Chronic RU486 administration in two patients with ectopic secretion of adrenocorticotropin (ACTH) has been associated with decreasing plasma cortisol concentrations. One explanation of this finding is that RU486 may directly inhibit adrenal steroidogenesis. To test this hypothesis, we measured the effect of RU486 on specific steroidogenic enzymatic steps using an in vivo rat and an in vitro monkey model. Hypophysectomized-castrated-ACTH-replaced Sprague-Dawley rats were given RU486 i.p. at daily doses of 0, 0.0005, 0.005, 0.05, 0.5 and 5 mg/kg body weight per day for 7 days. The animals were sacrificed, and blood and adrenal glands collected. Adrenal cortical mitochondria and microsomes were purified from the rats and from two untreated Cynomolgus macaque monkeys. Specific steroidogenic enzyme activities were measured in the rat by the incorporation of C-14-labeled steroid substrates into products. A similar protocol was used to assay the steroidogenesis in the monkey adrenal fractions in the presence and absence of added RU486. Although rat adrenal weights decreased significantly at the highest RU486 dose, plasma levels of corticosterone were similar in control and treated rats. Rat adrenal 3 beta-hydroxysteroid dehydrogenase/isomerase (3-HSD), 21-hydroxylase (21-OH) and 11-hydroxylase (11-OH) activities decreased with increasing RU486 doses, with 21-OH and 11-OH being most severely affected. Monkey adrenal 3-HSD, 21-OH, 11-OH, 17-hydroxylase and 17,20-desmolase similarly decreased in the presence of increasing in vitro concentrations of RU486. Taken together, these results suggest that RU486 directly inhibits adrenal steroidogenesis, with a locus of action at several key enzymatic steps in the glucocorticoid pathway. This steroidogenic blockade may account for the observed decreases in glucocorticoids during RU486 treatment. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 22 TC 15 Z9 15 U1 0 U2 1 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD FEB PY 1994 VL 130 IS 2 BP 195 EP 200 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NK510 UT WOS:A1994NK51000014 PM 8130896 ER PT J AU COHEN, PJ COHEN, PA ROSENBERG, SA KATZ, SI MULE, JJ AF COHEN, PJ COHEN, PA ROSENBERG, SA KATZ, SI MULE, JJ TI MURINE EPIDERMAL LANGERHANS CELLS AND SPLENIC DENDRITIC CELLS PRESENT TUMOR-ASSOCIATED ANTIGENS TO PRIMED T-CELLS SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE LANGERHANS CELLS; DENDRITIC CELLS; TUMOR IMMUNITY; TUMOR-ASSOCIATED ANTIGENS ID INFILTRATING LYMPHOCYTES; PULMONARY METASTASES; PROTECTIVE IMMUNITY; NECROSIS-FACTOR; INVIVO; INDUCTION; CLONES; MOUSE; IMMUNOTHERAPY; STIMULATION AB We examined the ability of epidermal Langerhans cells and splenic dendritic cells to present tumor-associated antigens (Ag) to immune T cells. Methylcholanthrene (MCA)-induced subcutaneous fibrosarcomas derived from C57BL/6 mice were used as tumor models. Our data demonstrate that both murine Langerhans cells and splenic dendritic cells have the capacity to present tumor-associated Ag to primed T cells. We found that variously treated tumor preparations (irradiated viable tumor cells, irradiated frozen-stored tumor cells, mitomycin C-treated viable tumor cells, and snap freeze-thawed tumor cell lysates) can be utilized for tumor Ag-pulsing. Primed CD4(+) T cells demonstrated in vitro specificity towards their respective tumors and did not cross-react to other syngeneic MCA-induced or non-MCA-induced tumors. The T cell proliferative response critically depended on the presence of immune CD4(+) T cells. We discuss the implications of these findings for the adoptive immunotherapy of cancer using immune CD4(+) T cells. C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. NR 38 TC 111 Z9 111 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD FEB PY 1994 VL 24 IS 2 BP 315 EP 319 DI 10.1002/eji.1830240206 PG 5 WC Immunology SC Immunology GA MW383 UT WOS:A1994MW38300005 PM 7905414 ER PT J AU LI, Q ABE, T KIKUCHI, T NUSSENBLATT, RB SHINOHARA, T CHAN, CC AF LI, Q ABE, T KIKUCHI, T NUSSENBLATT, RB SHINOHARA, T CHAN, CC TI CORTICOSTEROIDS ENHANCE S-ANTIGEN EXPRESSION IN NONRETINAL OCULAR-TISSUES OF RATS WITH EXPERIMENTAL AUTOIMMUNE UVEITIS SO EXPERIMENTAL AND MOLECULAR PATHOLOGY LA English DT Article ID RETINAL ANTIGENS; UVEORETINITIS; INHIBITION; INDUCTION; DISEASE AB S-antigen (S-Ag), a major protein on the retinal photoreceptor cell, can induce experimental autoimmune uveitis (EAU). We have previously detected S-Ag and its mRNA in irises of chronic uveitis patients receiving long-term steroid therapy. To further investigate the effect of steroid therapy on ocular tissue, we compared levels of S-Ag and its mRNA in EAU rats with and without steroid treatment. EAU was induced in 72 Lewis rats by two footpad injections of S-Ag. The rats were then treated with Depo-Medrol or phosphate-buffered saline by intramuscular injection. Eyes were collected at different time points. S-Ag mRNA was detected in the lens epithelium, trabecular meshwork, iris, and ciliary body of 47.2% of the steroid-treated group vs 22.2% of the controls. S-antigen was also detected in 30.6% of the eyes of the treated group vs 16.7% of the controls. S-Ag and its mRNA was found only in the retina of normal rats. These results support the hypothesis that prolonged corticosteroid therapy in uveitic patients might enhance the expression of S-Ag in nonretinal ocular tissues and might contribute to the ocular side effects of corticosteroid.(C) 1994 Academic Press, Inc. C1 NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. RP LI, Q (reprint author), NEI,IMMUNOL LAB,BETHESDA,MD 20892, USA. OI Shinohara, Toshimichi/0000-0002-7197-9039 NR 24 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4800 J9 EXP MOL PATHOL JI Exp. Mol. Pathol. PD FEB PY 1994 VL 60 IS 1 BP 27 EP 38 DI 10.1006/exmp.1994.1003 PG 12 WC Pathology SC Pathology GA NK869 UT WOS:A1994NK86900003 PM 8162968 ER PT J AU WEGHORST, CM DEVOR, DE HENNEMAN, JR WARD, JM AF WEGHORST, CM DEVOR, DE HENNEMAN, JR WARD, JM TI PROMOTION OF HEPATOCELLULAR FOCI AND ADENOMAS BY DI(2-ETHYLHEXYL)PHTHALATE AND PHENOBARBITAL IN C3H/HENCR MICE FOLLOWING EXPOSURE TO N-NITROSODIETHYLAMINE AT 15 DAYS OF AGE SO EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY LA English DT Article DE C3H/HENCR MICE; LIVER TUMOR PROMOTION; DI(2-ETHYLHEXYL)PHTHALATE, DEHP; PHENOBARBITAL; HEPATOCELLULAR FOCI; ADENOMA, HEPATOCELLULAR; N-NITROSODIETHYLAMINE; PROMOTERS, HEPATIC TUMOR; HEPATIC TUMOR PROMOTERS ID MALE B6C3F1 MICE; LIVER-TUMORS; RAT-LIVER; DIETHYLNITROSAMINE; HEPATOCARCINOGENESIS; SUSCEPTIBILITY; JUVENILE; LESIONS AB Previous studies have shown that phenobarbital (PB), as well as another known liver tumor promoter, alpha-hexachlorocyclohexane (HCH), inhibits hepatic tumor formation in infant N-nitrosodiethylamine (NDEA)-initiated C57BL/6 x C3H/He (B6C3F1) male mice. These inconsistencies in detecting PB and HCH as tumor promoters have raised important questions on the mechanism of tumor promotion in mice, as well as the reliability of the infant B6C3F1 mouse as an initiation model in two-stage carcinogenesis experiments. Therefore, in an effort to avoid the inconsistencies associated with the B6C3F1 mouse, the present study evaluated the ability of two known hepatic liver tumor promoters, di(2-ethylhexyl)phthalate (DEHP), a peroxisome proliferator, and phenobarbital (PB), a barbiturate, to promote hepatocellular tumorigenesis in mice of the C3H/HeNCr strain initiated during infancy. At 15 days of age, male and female C3H/HeNCr mice received either a single ip injection of NDEA (5 mu g/g body weight) or saline. At weaning (4 weeks of age), mice were divided into 3 groups and treated with either DEHP in the diet (12,000 ppm), PB in the drinking water (500 ppm), or control drinking water and diet for 24 weeks. All mice were killed at 28 weeks of age and the number and size of hepatic foci and adenomas were evaluated. Mice exposed to NDEA+DEHP or NDEA+PB showed significant increases in the number and size of hepatic tumors compared to those receiving NDEA alone. DEHP treatment in males yielded larger adenomas than those seen in PB-treated males. Histologically, foci and adenomas generated in NDEA+DEHP-treated mice were hyperbasophilic compared to the typically basophilic lesions in NDEA only-treated mice, while NDEA+PB-treated mice exhibited predominantly eosinophilic foci and adenomas. This study demonstrates that the infant NDEA-initiated C3H/HeNCr mouse is extremely sensitive to the promoting effects of two classes of known mouse liver tumor promoters and suggests that the C3H/HeNCr mouse may be a more suitable strain to utilize in the infant initiated mouse model for the detection of potential hepatic tumor promoters. C1 NCI,DIV CANC ETIOL,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RP WEGHORST, CM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702, USA. NR 30 TC 3 Z9 3 U1 0 U2 1 PU GUSTAV FISCHER VERLAG JENA PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0940-2993 J9 EXP TOXICOL PATHOL JI Exp. Toxicol. Pathol. PD FEB PY 1994 VL 45 IS 7 BP 423 EP 431 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA NA695 UT WOS:A1994NA69500005 PM 8167465 ER PT J AU SAUNDERS, RC KOLACHANA, BS WEINBERGER, DR AF SAUNDERS, RC KOLACHANA, BS WEINBERGER, DR TI LOCAL PHARMACOLOGICAL MANIPULATION OF EXTRACELLULAR DOPAMINE LEVELS IN THE DORSOLATERAL PREFRONTAL CORTEX AND CAUDATE-NUCLEUS IN THE RHESUS-MONKEY - AN IN-VIVO MICRODIALYSIS STUDY SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE MICRODIALYSIS; DOPAMINE; CAUDATE; PREFRONTAL CORTEX; MONKEY ID BRAIN MICRODIALYSIS; D-AMPHETAMINE; DIALYSIS; RELEASE; METABOLITES; DIALYTRODE; COCAINE; RATS AB The prefrontal cortex, caudate nucleus, and their dopaminergic innervations have been implicated in complex information processing. The present study utilized the in vivo microdialysis technique to characterize the extracellular dopamine levels in the prefrontal cortex and the caudate nucleus in the rhesus monkey. Basal levels of dopamine were consistently found in the caudate nucleus, while levels in the prefrontal cortex were less reliably measured. Manipulation of dopamine levels using tetrodotoxin and high potassium demonstrated that dopamine measured was dependent on neuronal firing. Administration of indirect dopamine agonists d-amphetamine and cocaine into the prefrontal cortex and the caudate nucleus increased extracellular dopamine levels 250% and 5000%, respectively. Amphetamine and cocaine had greater effects on dopamine levels in the caudate than in the prefrontal cortex. Cocaine induced increases appeared to be less than that of amphetamine and the actions of cocaine lasted longer than amphetamine. This study demonstrates the feasibility of using in vivo microdialysis in monitoring neurochemicals in different regions of the rhesus monkey brain. RP SAUNDERS, RC (reprint author), ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,IRP,CLIN BRAIN DISORDERS,WASHINGTON,DC 20032, USA. NR 28 TC 25 Z9 25 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD FEB PY 1994 VL 98 IS 1 BP 44 EP 52 PG 9 WC Neurosciences SC Neurosciences & Neurology GA NC428 UT WOS:A1994NC42800006 PM 8013591 ER PT J AU LUYTEN, FP CHEN, P PARALKAR, V REDDI, AH AF LUYTEN, FP CHEN, P PARALKAR, V REDDI, AH TI RECOMBINANT BONE MORPHOGENETIC PROTEIN-4, TRANSFORMING GROWTH-FACTOR-BETA(1), AND ACTIVIN-A ENHANCE THE CARTILAGE PHENOTYPE OF ARTICULAR CHONDROCYTES IN-VITRO SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID TGF-BETA FAMILY; BOVINE OSTEOGENIC PROTEIN; DIFFERENTIATION INVITRO; VENTRALIZING FACTOR; MESSENGER-RNA; MESODERM; RECEPTORS; IDENTIFICATION; PROLIFERATION; PROTEOGLYCANS C1 JOHNS HOPKINS UNIV,SCH MED,DEPT ORTHOPED SURG,MUSCULOSKELETAL CELL BIOL LAB,BALTIMORE,MD 21218. RP LUYTEN, FP (reprint author), NIDR,BONE RES BRANCH,BLDG 10,ROOM 1N108,BETHESDA,MD 20892, USA. NR 31 TC 113 Z9 115 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD FEB PY 1994 VL 210 IS 2 BP 224 EP 229 DI 10.1006/excr.1994.1033 PG 6 WC Oncology; Cell Biology SC Oncology; Cell Biology GA MV440 UT WOS:A1994MV44000012 PM 8299720 ER PT J AU STRAIN, AJ MCGUINNESS, G RUBIN, JS AARONSON, SA AF STRAIN, AJ MCGUINNESS, G RUBIN, JS AARONSON, SA TI KERATINOCYTE GROWTH-FACTOR AND FIBROBLAST GROWTH-FACTOR ACTION ON DNA-SYNTHESIS IN RAT AND HUMAN HEPATOCYTES - MODULATION BY HEPARIN SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID FULMINANT HEPATIC-FAILURE; LIVER-REGENERATION; PRIMARY CULTURES; EPITHELIAL-CELLS; BINDING; PURIFICATION; VASOPRESSIN; RECEPTOR; BETA; STIMULATION C1 QUEEN ELIZABETH HOSP,LIVER RES LABS,BIRMINGHAM B15 2TH,W MIDLANDS,ENGLAND. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP STRAIN, AJ (reprint author), UNIV BIRMINGHAM,SCH BIOCHEM,BIRMINGHAM B15 2TH,W MIDLANDS,ENGLAND. FU Wellcome Trust NR 39 TC 36 Z9 37 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD FEB PY 1994 VL 210 IS 2 BP 253 EP 259 DI 10.1006/excr.1994.1037 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA MV440 UT WOS:A1994MV44000016 PM 7507851 ER PT J AU BETTELHEIM, FA REID, MB GARLAND, D AF BETTELHEIM, FA REID, MB GARLAND, D TI HYDRATION OF GAMMA-CRYSTALLINS SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE BOUND WATER; FREEZABLE WATER; GAMMA-CRYSTALLINS; HYDRATION; LENS ID LENS PROTEIN SOLUTIONS; CALF EYE LENS; II CRYSTALLIN; TERTIARY STRUCTURE; WATER-CONTENT; STABILITY; TRYPTOPHAN; RESOLUTION; SECONDARY; CATARACT C1 NEI,BETHESDA,MD 20892. RP BETTELHEIM, FA (reprint author), ADELPHI UNIV,DEPT CHEM,GARDEN CITY,NY 11530, USA. FU NEI NIH HHS [EY-02571] NR 33 TC 4 Z9 4 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD FEB PY 1994 VL 58 IS 2 BP 219 EP 223 DI 10.1006/exer.1994.1010 PG 5 WC Ophthalmology SC Ophthalmology GA MY755 UT WOS:A1994MY75500010 PM 8157114 ER PT J AU KHACHATURIAN, ZS AF KHACHATURIAN, ZS TI HYPOTHESIS - MICROTUBULE INSTABILITY AND PAIRED HELICAL FILAMENT FORMATION IN THE ALZHEIMER-DISEASE BRAIN ARE RELATED TO APOLIPOPROTEIN-E GENOTYPE - COMMENT SO EXPERIMENTAL NEUROLOGY LA English DT Editorial Material RP KHACHATURIAN, ZS (reprint author), NIA,NEUROSCI & NEUROPSYCHOL AGING PROGRAM,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD FEB PY 1994 VL 125 IS 2 BP 174 EP 174 DI 10.1006/exnr.1994.1021 PG 1 WC Neurosciences SC Neurosciences & Neurology GA MY090 UT WOS:A1994MY09000003 ER PT J AU MOWATT, MR WEINBACH, EC HOWARD, TC NASH, TE AF MOWATT, MR WEINBACH, EC HOWARD, TC NASH, TE TI COMPLEMENTATION OF AN ESCHERICHIA-COLI GLYCOLYSIS MUTANT BY GIARDIA-LAMBLIA TRIOSEPHOSPHATE ISOMERASE SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE TIM; TPI; EC 5.3.1.1; PCR; PRIMER EXTENSION; GENE EXPRESSION ID EXPRESSION; SEQUENCES; GENE; PROTEINS; CLONING; PATHWAY; CHICKEN; RNA RP MOWATT, MR (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 35 TC 43 Z9 45 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD FEB PY 1994 VL 78 IS 1 BP 85 EP 92 DI 10.1006/expr.1994.1008 PG 8 WC Parasitology SC Parasitology GA MW550 UT WOS:A1994MW55000008 PM 8299763 ER PT J AU KEISTER, DB KASLOW, DC AF KEISTER, DB KASLOW, DC TI CRYOPRESERVATION OF PLASMODIUM-FALCIPARUM GAMETOCYTES SO EXPERIMENTAL PARASITOLOGY LA English DT Note ID MALARIA RP KEISTER, DB (reprint author), NIAID,MALARIA RES LAB,MOLEC VACCINE SECT,BETHESDA,MD, USA. NR 5 TC 3 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD FEB PY 1994 VL 78 IS 1 BP 118 EP 119 DI 10.1006/expr.1994.1012 PG 2 WC Parasitology SC Parasitology GA MW550 UT WOS:A1994MW55000012 PM 7905424 ER PT J AU OPPENHEIM, JJ NETA, R AF OPPENHEIM, JJ NETA, R TI PATHOPHYSIOLOGICAL ROLES OF CYTOKINES IN DEVELOPMENT, IMMUNITY, AND INFLAMMATION SO FASEB JOURNAL LA English DT Article ID T-CELLS; SUBSETS; MOUSE AB The symposium on The Role of Cytokines in Inflammation held at The American Association of Immunologists meeting in Denver, Colorado on May 25, 1993, was organized by Drs. Maureen Howard and Joost J. Oppenheim to reflect 30 years of progress in the field. Dr. John David, who first reported a cytokine, macrophage migration inhibitory factor (MIF),(2) reviewed the subsequent isolation, sequencing, cDNA cloning, expression, and characterization of this pioneer among cytokines. The properties of interleukins-12 and -13 (IL-12, IL-13) were presented by their discoverers, Drs. Maurice Gately and Gerard Zurawski, respectively. Two speakers addressed the pathophysiological roles of tumor growth factor beta (TGF beta), a pluripotent cytokine with contrasting anti-inflammatory and immunoenhancing properties. Dr. Ron Diebold's studies of mice deficient in TGF beta 1 document the crucial anti-inflammatory role of this cytokine in normal animals whereas Dr. Sharon Wahl's studies of the role of TGF beta in arthritis reveal the proinflammatory propensities. Studies of the role of cytokines in immunodeficient mice by Dr. Emil Unanue revealed their pivotal role in early nonimmunological host defense processes. Dr. Scott Durum elucidated crucial roles for cytokines in the development of the immune system by inducing rearrangement of the T cell receptor gene in thymocytes. Finally, the immunoregulatory roles of TH1 or TH2 cytokines were considered by Drs. Robert Modlin and Gene Shearer to determine whether cellular or humoral immunity prevails in infectious diseases such as leprosy, leishmaniasis, tuberculosis, and AIDS. C1 ARMED FORCES RADIOBIOL RES INST,BETHESDA,MD 20814. RP OPPENHEIM, JJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701, USA. NR 28 TC 42 Z9 42 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD FEB PY 1994 VL 8 IS 2 BP 158 EP 162 PG 5 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA MY299 UT WOS:A1994MY29900021 PM 8119486 ER PT J AU OEHNINGER, S BLACKMORE, P MORSHEDI, M SUELDO, C ACOSTA, AA ALEXANDER, NJ AF OEHNINGER, S BLACKMORE, P MORSHEDI, M SUELDO, C ACOSTA, AA ALEXANDER, NJ TI DEFECTIVE CALCIUM INFLUX AND ACROSOME REACTION (SPONTANEOUS AND PROGESTERONE-INDUCED) IN SPERMATOZOA OF INFERTILE MEN WITH SEVERE TERATOZOOSPERMIA SO FERTILITY AND STERILITY LA English DT Article DE TERATOZOOSPERMIA; CALCIUM INFLUX; ACROSOME REACTION; PROGESTERONE; CALCIUM IONOPHORE ID ABNORMAL SPERM MORPHOLOGY; HUMAN ZONA-PELLUCIDA; INVITRO FERTILIZATION; OLIGOZOOSPERMIC MEN; SEMEN; ASSAY AB Objective: To evaluate the acrosome reaction and its prerequisite, a calcium influx, in spermatozoa of infertile men with a high incidence of abnormal sperm forms. Design: Prospective, controlled study. Setting: Academic tertiary assisted reproduction center. Patients: Patients (n = 14) were allocated in the study after semen evaluation showed teratozoospermia (<14% normal sperm forms) as diagnosed by strict criteria. Interventions: After swim-up separation of the motile fraction, acrosome reactions were evaluated using Pisum sativum agglutinin (both spontaneously and exogenously induced with P and the calcium ionophore A23187, both at 10 mu M); the intracellular-free [Ca2+](i) was assessed by the fluorescent fura-2 indicator (basal and after P). Results: Patients did not show the typical P-induced wave of [Ca2+](i) that was observed in controls but rather a blunted response, no response at all, or abnormal basal [Ca2+](i), levels. The percent of basal acrosome reaction was significantly lower for patients versus controls postswim-up, and at 1 hour and 3 hours. Furthermore, there was a significant difference in the response of acrosome reaction to P both at 1 hour and 3 hours, with patients showing almost no response at all. However, patients' acrosome reaction response to the calcium ionophore was similar to those of fertile men. Conclusion: Infertile patients with a high incidence of abnormal sperm forms as diagnosed by strict criteria have a low incidence of spontaneous acrosome reaction and a diminished P-stimulated acrosome reaction, whereas the nonspecific response to a calcium ionophore is conserved. Parallel abnormalities of [Ca2+](i) were observed in patients, suggesting that these sperm populations may have a defective nongenomic P sperm receptor and/or abnormalities of other membrane transduction systems. C1 UNIV CALIF SAN FRANCISCO,DEPT OBSTET & GYNECOL,SAN FRANCISCO,CA. NICHHD,BETHESDA,MD. EASTERN VIRGINIA MED SCH,JONES INST REPROD MED,DEPT PHARMACOL,NORFOLK,VA. RP OEHNINGER, S (reprint author), EASTERN VIRGINIA MED SCH,JONES INST REPROD MED,DEPT OBSTET & GYNECOL,601 COLLEY AVE,NORFOLK,VA 23507, USA. NR 24 TC 71 Z9 73 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 FEB PY 1994 VL 61 IS 2 BP 349 EP 354 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA MV788 UT WOS:A1994MV78800024 PM 8299795 ER PT J AU BLAZKA, ME DIXON, D HASKINS, E ROSENTHAL, GJ AF BLAZKA, ME DIXON, D HASKINS, E ROSENTHAL, GJ TI PULMONARY TOXICITY TO INTRATRACHEALLY ADMINISTERED INDIUM TRICHLORIDE IN FISCHER-344 RATS SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID AMINOLEVULINIC-ACID DEHYDRATASE; MACROPHAGE FIBRONECTIN RELEASE; ALVEOLAR MACROPHAGE; GALLIUM-ARSENIDE; LUNG INJURY; CHLORIDE; FIBROSIS; SILICA AB The use of indium by the semiconductor industry has risen sharply in recent years with the discovery that the electrical properties of compounds such as indium phosphide and indium arsenide are better than those of silicon. However, relatively little is known about its potential to induce lung damage. These studies examined the effect of indium trichloride (InCl3) on the lung. To examine the disposition and removal of InCl3 from the lung, groups of female Fischer 344 rats received a single intratracheal dose of 1.3 mg In/kg as InCl3 and were euthanized after 1, 2, 4, 7, 14, 28, and 56 days at which time lung samples were analyzed for metal content. Furthermore, the histology, hydroxyproline levels, and bronchoalveolar lavage (BAL) fluid cellularity of the lung were studied. In addition, the effect of 0.00016, 0.00325, 0.065, and 1.3 mg In/kg on inflammatory response and BAL fluid cellularity was compared. While a dose as low as 0.00325 mg In/kg was capable of initiating an influx of inflammatory cells, instillation of 1.3 mg In/kg resulted in an inflammatory response that was still evident 56 days later. After 28 days, the lung weight of the InCl3-treated animals was 2.5 times greater than that of the controls. The total cell number in the BAL fluid of the treated animals after 28 days was 32 times higher than that in the control rats. Sixty-seven percent of these cells were granulocytes. Compared to the controls, the hydroxyproline content of the lungs from the InCl3-treated animals were twofold greater after 28 and 56 days. Furthermore, the levels of fibronectin and TNF alpha present in the BAL fluid of InCl3-treated rats increased sharply during the first 24 hr and remained elevated 56 days later. These data and the histological examination of the lung following InCl3 treatment suggest that InCl3 is capable of causing severe lung damage and the development of fibrosis. (C) 1994 Society of Toxicology. C1 NIEHS,EXPTL PATHOL LAB,RES TRIANGLE PK,NC 27709. NIEHS,EXPTL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. RP BLAZKA, ME (reprint author), NIEHS,ENVIRONM IMMUNOL & NEUROBIOL SECT,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 35 TC 26 Z9 28 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD FEB PY 1994 VL 22 IS 2 BP 231 EP 239 DI 10.1006/faat.1994.1027 PG 9 WC Toxicology SC Toxicology GA MZ249 UT WOS:A1994MZ24900008 PM 8005375 ER PT J AU DEGREGORI, J RUSS, A VONMELCHNER, H RAYBURN, H PRIYARANJAN, P JENKINS, NA COPELAND, NG RULEY, HE AF DEGREGORI, J RUSS, A VONMELCHNER, H RAYBURN, H PRIYARANJAN, P JENKINS, NA COPELAND, NG RULEY, HE TI A MURINE HOMOLOG OF THE YEAST RNA1 GENE IS REQUIRED FOR POSTIMPLANTATION DEVELOPMENT SO GENES & DEVELOPMENT LA English DT Article DE FUG1; YEAST RNA1; MOUSE DEVELOPMENT; LEUCINE RICH MOTIFS; INSERTIONAL MUTAGENESIS ID EMBRYONIC STEM-CELLS; RETROVIRUS PROMOTER-TRAP; DNA METHYLATION; MOUSE EMBRYO; LINKAGE MAP; IDENTIFICATION; INITIATION; CLONING; PROTEIN; GENOME AB A gene has been characterized that is required for postimplantation mouse development. The gene, designated fug1, was disrupted in embryonic stem cells by the U3Neo gene trap retrovirus, and the disrupted allele was introduced into the germ line. Homozygous mutant embryos arrest at the egg cylinder stage at about embryonic day 6 and are mostly resorbed by day 8.5. The appearance of the proamniotic cavity is delayed, and epiblast cells that surround the cavity are disorganized. fug1 transcripts are undetectable at Eb but are induced throughout the embryo after E6.5. The gene is expressed at low levels in all adult tissues examined, maps to chromosome 15, and is conserved among mammals. The cDNA sequence encodes a protein of 589 amino acids, the first 400 of which are 38% identical to the Saccaromyces cerevisiae RNA1 gene. Regions of greatest similarity include a long acidic domain and 11 leucine-rich motifs, thought to mediate high affinity protein-protein interactions. These similarities suggest that Fug1 may be required for developmental changes in RNA processing or chromatin structure prior to gastrulation. C1 VANDERBILT UNIV, SCH MED, DEPT MICROBIOL & IMMUNOL, NASHVILLE, TN 37232 USA. MIT, CTR CANC RES, CAMBRIDGE, MA 02139 USA. MIT, DEPT BIOL, CAMBRIDGE, MA 02139 USA. UNIV FRANKFURT, SCH MED, DEPT HEMATOL, W-6000 FRANKFURT 70, GERMANY. NCI, FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB, ABL,BASIC RES PROGRAM, FREDERICK, MD 21702 USA. FU NCI NIH HHS [N01-CO-74101]; NIGMS NIH HHS [R01GM84688] NR 47 TC 88 Z9 90 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD FEB 1 PY 1994 VL 8 IS 3 BP 265 EP 276 DI 10.1101/gad.8.3.265 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA MY086 UT WOS:A1994MY08600002 PM 8314081 ER PT J AU KOOP, BF ROWEN, L WANG, K KUO, CL SETO, D LENSTRA, JA HOWARD, S SHAN, W DESHPANDE, P HOOD, L AF KOOP, BF ROWEN, L WANG, K KUO, CL SETO, D LENSTRA, JA HOWARD, S SHAN, W DESHPANDE, P HOOD, L TI THE HUMAN T-CELL RECEPTOR TCRAC/TCRDC (C-ALPHA/C-DELTA) REGION - ORGANIZATION, SEQUENCE, AND EVOLUTION OF 97.6 KB OF DNA SO GENOMICS LA English DT Review ID VARIABLE REGION GENES; ALPHA-CHAIN GENE; COMPLETE NUCLEOTIDE-SEQUENCE; PROTEIN-CODING REGIONS; ALU-ALU RECOMBINATION; ANTIGEN RECEPTOR; DELTA-CHAIN; CHROMOSOME-14 INVERSION; V-ALPHA; TRANSCRIPTIONAL ENHANCER AB We sequenced and analyzed 97.6 kb of new DNA sequence containing the human TCRAC (C alpha) and TCRDC (C delta) genes as well as the TCRDV3 (V delta 3) and 61 different TCRAJ (J alpha) gene segments and compared its organization and structure to the previously described mouse T-cell receptor TCRAC/TCRDC (C alpha/C delta) region. A comprehensive nomenclature, consistent with the IUIS nomenclature committee recommendations, for both human and mouse TCRAJ gene segments is presented. In the human sequence, we identified 20 new TCRAJ gene segments and obtained the germline sequence for 23 additional TCRAJ gene segments known from cDNA clones. Using the sequence data obtained from the human TCRAC/TCRDC region, we have extended a polymerase chain reaction-based assay to test for the expression of the individual TCRAJ gene segments. At least five TCRAJ pseudogene segments were identified by sequence criteria. Like the murine TCRAC/TCRDC sequence, this sequence contains a high level of coding sequence, with over 6.6% of the total sequence being transcribed. Comparison of the human sequence with the previously reported mouse DNA sequence reveals homologous counterparts for the variable and joining (J) gene segments and both constant genes. Eleven new J pseudogene segments have been identified in the mouse TCRAC/TCRDC sequence through the use of human and mouse sequence comparisons. In terms of structure and organization, this region of the human and mouse genome appears to be remarkably conserved. (C) 1994 Academic Press, Inc. C1 UNIV WASHINGTON,DEPT MOLEC BIOTECHNOL,SEATTLE,WA 98195. CALTECH,DIV BIOL 13974,PASADENA,CA 91125. NIH,DIV ENDOCRINOL,BETHESDA,MD 20892. DEPT INFECT DIS & IMMUNOL,3508 TD UTRECHT,NETHERLANDS. RP KOOP, BF (reprint author), UNIV VICTORIA,CTR ENVIRONM HLTH,DEPT BIOL,VICTORIA V8W 2Y2,BC,CANADA. RI Koop, Ben/A-8151-2008 OI Koop, Ben/0000-0003-0045-5200 NR 138 TC 169 Z9 177 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD FEB PY 1994 VL 19 IS 3 BP 478 EP 493 DI 10.1006/geno.1994.1097 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NA605 UT WOS:A1994NA60500010 PM 8188290 ER PT J AU CECI, JD MATSUDA, Y GRUBBER, JM JENKINS, NA COPELAND, NG CHAPMAN, VM AF CECI, JD MATSUDA, Y GRUBBER, JM JENKINS, NA COPELAND, NG CHAPMAN, VM TI INTERSPECIFIC BACKCROSSES PROVIDE AN IMPORTANT NEW TOOL FOR CENTROMERE MAPPING OF MOUSE CHROMOSOMES SO GENOMICS LA English DT Article ID GENETIC-LINKAGE MAP; SATELLITE DNA; ALPHA-SUBUNIT; MUS-MUSCULUS; PLASMINOGEN-ACTIVATOR; TRANSFORMING ACTIVITY; MOLECULAR-CLONING; OVARIAN TERATOMA; T-HAPLOTYPES; X-CHROMOSOME AB Centromere mapping of mouse chromosomes has been problematic due to a paucity of appropriate markers. As a result, the mapping of centromeres has most often relied on the use of Robertsonian chromosomes to mark chromosome ends. Many Robertsonian translocations have been shown to suppress recombination in pericentric regions; therefore, centromere mapping data generated by using Robertsonian chromosomes must be interpreted with caution. We have utilized a new tool for centromere mapping that is applicable to all mouse chromosomes (except the Y chromosome) and that potentially overcomes the inherent limitations of using Robertsonian translocations. Briefly, an interspecific backcross mapping panel was constructed from crosses of C57BL/6Ros and Mus spretus mice. The centromere of each chromosome was subsequently typed by in situ hybridization, using a major satellite probe that uniformly labels C57BL/6Ros centromeres but hybridizes only weakly to M. spretus centromeres. Genetic markers that were already known to map in the proximal region of each of the mouse chromosomes were then typed by segregation analyses of restriction fragment length polymorphisms. These studies have made it possible to align the interspecific genetic map of each of the mouse autosomes and the X chromosome with respect to the centromere. They also provide a basis for comparison with centromere mapping data generated previously by other means. (C) 1994 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. NATL INST RADIOL SCI,DIV GENET,CHIBA 263,JAPAN. ROSWELL PK MEM CANC INST,DEPT MOLEC & CELLULAR BIOL,BUFFALO,NY 14263. FU NCI NIH HHS [N01-CO-74101]; NHGRI NIH HHS [HG-00170]; NIGMS NIH HHS [GM-33160] NR 80 TC 16 Z9 16 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD FEB PY 1994 VL 19 IS 3 BP 515 EP 524 DI 10.1006/geno.1994.1101 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NA605 UT WOS:A1994NA60500014 PM 8188294 ER PT J AU AIDA, K MOORE, R NEGISHI, M AF AIDA, K MOORE, R NEGISHI, M TI LACK OF THE STEROID 15-ALPHA-HYDROXYLASE GENE (CYP2A-4) IN WILD MOUSE STRAIN MUS-SPRETUS - RAPID EVOLUTION OF THE P450 GENE SUPERFAMILY SO GENOMICS LA English DT Note ID COUMARIN 7-HYDROXYLASE; IDENTIFICATION; SEQUENCES; CYTOCHROME-P-450; ACID AB Steroid 15 alpha-hydroxylase P450(15 alpha) and coumarin 7-bydroxylase P450coh genes Cyp2a-4 and Cyp2a-5 are members of the mouse P450 2A subfamily. Whereas Mus musclus domesticus strains contain both genes, wild mouse strain Mus spretus contains only Cyp2a-5. Evolutionarily, therefore, Cyp2a-5 is ancestral to Cyp2a-4. Moreover, the line to Cyp2a-4 descended as recently as 3 million years ago in an ancestral mouse. This evidence implies a rapid evolution of the P450 gene superfamily. (C) 1994 Academic Press, Inc. C1 NIEHS,REPROD & DEV TOXICOL LAB,PHARMACOGENET SECT,RES TRIANGLE PK,NC 27709. NR 14 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD FEB PY 1994 VL 19 IS 3 BP 564 EP 566 DI 10.1006/geno.1994.1107 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NA605 UT WOS:A1994NA60500020 PM 8188299 ER PT J AU OHAMA, T CHOI, IS HATFIELD, DL JOHNSON, KR AF OHAMA, T CHOI, IS HATFIELD, DL JOHNSON, KR TI MOUSE SELENOCYSTEINE TRNA([SER]SEC) GENE (TRSP) AND ITS LOCALIZATION ON CHROMOSOME-7 SO GENOMICS LA English DT Note ID TRANSFER-RNA GENE C1 NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. JACKSON LAB,BAR HARBOR,ME 04609. FU NIGMS NIH HHS [GM46697] NR 13 TC 18 Z9 18 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD FEB PY 1994 VL 19 IS 3 BP 595 EP 596 DI 10.1006/geno.1994.1116 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NA605 UT WOS:A1994NA60500029 PM 8188307 ER PT J AU HORNBROOK, MC STEVENS, VJ WINGFIELD, DJ HOLLIS, JF GREENLICK, MR ORY, MG AF HORNBROOK, MC STEVENS, VJ WINGFIELD, DJ HOLLIS, JF GREENLICK, MR ORY, MG TI PREVENTING FALLS AMONG COMMUNITY-DWELLING OLDER PERSONS - RESULTS FROM A RANDOMIZED TRIAL SO GERONTOLOGIST LA English DT Article DE INJURIES; HEALTH BEHAVIOR; EXERCISE; WALKING; HOME SAFETY; ENVIRONMENT ID RISK-FACTORS; ELDERLY PERSONS; POPULATION AB A randomized trial of a falls prevention program that addressed home safety, exercise, and behavioral risks was conducted with 3,182 independently living HMO members age 65 and older. The intervention decreased the odds of falling by 0.85, but only reduced the average number of falls among those who fell by 7%. The effect was strongest among men age 75 and older. The likelihood of avoiding falls requiring medical treatment was not significantly affected by the intervention. We conclude that the intervention dose was not of sufficient intensity or duration to have a marked protective effect on older persons. Future research should focus on more intensive intervention approaches because serious falls do not appear to be amenable to low-intensity environment/behavioral efforts. C1 NIA,BEHAV & SOCIAL RES,BETHESDA,MD 20892. OREGON HLTH SCI UNIV,SCH NURSING,DEPT COMMUNITY HLTH CARE SYST,PORTLAND,OR 97201. OREGON HLTH SCI UNIV,SCH MED,DEPT PUBL HLTH & PREVENT MED,PORTLAND,OR 97201. RP HORNBROOK, MC (reprint author), KAISER PERMANENTE,CTR HLTH RES,NW REG,3800 N KAISER CTR DR,PORTLAND,OR 97227, USA. FU NIA NIH HHS [1-U01-AG07670-01] NR 27 TC 302 Z9 306 U1 1 U2 18 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 FEB PY 1994 VL 34 IS 1 BP 16 EP 23 PG 8 WC Gerontology SC Geriatrics & Gerontology GA MX535 UT WOS:A1994MX53500003 PM 8150304 ER PT J AU HINRICHSEN, GA NIEDEREHE, G AF HINRICHSEN, GA NIEDEREHE, G TI DEMENTIA MANAGEMENT STRATEGIES AND ADJUSTMENT OF FAMILY MEMBERS OF OLDER PATIENTS SO GERONTOLOGIST LA English DT Article DE ADJUSTMENT; CAREGIVER; COPING; DEMENTIA; DEMENTIA MANAGEMENT STRATEGIES ID SEPARATION-INDIVIDUATION; ALZHEIMERS-DISEASE; CAREGIVING SPOUSES; PREDICTORS; GENDER; SAMPLE; BURDEN AB Family members caring for dementia patients must often contend with a complex set of behavioral problems evidenced by their demented older relatives. In this study we examined how strategies to manage dementia problems in (N = 152) older people were associated with the adjustment of family members while providing assistance to the patient. Three Dementia Management Strategies were identified (Criticism, Encouragement, and Active Management) and were found to be associated with three indices of family members' emotional adjustment -burden, psychiatric symptoms, and desire to institutionalize the patient. After controlling for the influence of family member and patient background characteristics and family member coping, Demential Management Strategies accounted for significant and unique variance in family members' burden and desire to institutionalize the patient but not in family members' psychiatric symptoms. The use of Active Management and Criticism was associated with greater burden, whereas use of encouragement was tied to less family member burden and less desire to institutionalize. C1 NIMH,ROCKVILLE,MD 20857. RP HINRICHSEN, GA (reprint author), HILLSIDE HOSP,GERIATR PSYCHIAT SERV,POB 38,GLEN OAKS,NY 11004, USA. NR 31 TC 78 Z9 84 U1 1 U2 7 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 FEB PY 1994 VL 34 IS 1 BP 95 EP 102 PG 8 WC Gerontology SC Geriatrics & Gerontology GA MX535 UT WOS:A1994MX53500013 PM 8150316 ER PT J AU RILEY, MW RILEY, JW AF RILEY, MW RILEY, JW TI AGE INTEGRATION AND THE LIVES OF OLDER-PEOPLE SO GERONTOLOGIST LA English DT Article; Proceedings Paper CT 1990 Madrid Meeting of the International-Sociological-Association CY 1990 CL MADRID, SPAIN SP INT SOCIOL ASSOC DE STRUCTURAL LAG; STRUCTURAL REVOLUTION; AGE DIFFERENTIATION; IDEAL TYPES; INTERVENTIONS ID LIFE COURSE AB This research-based essay argues, as a stimulus to Forum discussion, that our currently age-differentiated society will give way to an age-integrated one. Age will lose its power to constrain people's entry, exit, and performance in such basic social institutions as education, work, and retirement. Revolutionary changes toward age integration are needed to reduce the ''structural lag,'' in which the dynamism of human aging is outpacing the dynamism of structural change. To guide these changes, aging research is beginning to complement existing knowledge about human lives with new and deeper understanding of the social structures which shape and are shaped by these lives. RP RILEY, MW (reprint author), NIA,GATEWAY BLDG ROOM 2E206,7201 WISCONSIN AVE,BETHESDA,MD 20892, USA. NR 27 TC 51 Z9 52 U1 1 U2 5 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 FEB PY 1994 VL 34 IS 1 BP 110 EP 115 PG 6 WC Gerontology SC Geriatrics & Gerontology GA MX535 UT WOS:A1994MX53500015 PM 8150298 ER PT J AU GALLO, V WRIGHT, P MCKINNON, RD AF GALLO, V WRIGHT, P MCKINNON, RD TI EXPRESSION AND REGULATION OF A GLUTAMATE-RECEPTOR SUBUNIT BY BFGF IN OLIGODENDROCYTE PROGENITORS SO GLIA LA English DT Note DE O-2A PROGENITOR CELL; AMPA RECEPTORS; GLUTAMATE CHANNELS; GROWTH FACTORS ID AMINO-ACID RECEPTORS; GLIAL-CELLS; FUNCTIONAL EXPRESSION; CHANNEL EXPRESSION; MOLECULAR-CLONING; KAINATE RECEPTORS; GROWTH-FACTOR; HIGH-AFFINITY; CDNA CLONE; ASTROCYTES AB Oligodendrocyte progenitor cells (O-2A) express both kainate-preferring and AMPA-preferring glutamate receptors (Gallo et al., Sec. Neurosci. Abstr., 18:653, 1992b; Gallo et al., 1994). The expression and regulation of the GluR-4c, AMPA-preferring subunit by growth factors was studied by Northern blot analysis of total RNA from purified rat cortical O-2A progenitors. Differently from cortical neurons, O-2A progenitors only expressed two high molecular weight GluR-4c transcripts (6.2 and 4.2 kb), as observed also in cultured astrocytes. Basic fibroblast growth factor (bFGF) increased GluR-4c transcript levels in O-2A progenitors and its effects were not mimicked by platelet derived growth factor (PDGF) or fetal calf serum. Therefore, bFGF may regulate O-2A progenitor responsiveness to glutamate during development through the expression of glutamate receptor subunits. (C) 1994 Wiley-Liss, Inc. C1 NINCDS,VIRAL & MOLEC PATHOGENESIS LAB,BETHESDA,MD 20892. RP GALLO, V (reprint author), NICHHD,CELLULAR & MOLEC NEUROPHYSIOL LAB,NEUROBIOL UNIT,BLDG 49,ROOM 5A-78,BETHESDA,MD 20892, USA. RI McKinnon, Randall/B-4699-2010 NR 37 TC 31 Z9 31 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 0894-1491 J9 GLIA JI Glia PD FEB PY 1994 VL 10 IS 2 BP 149 EP 153 DI 10.1002/glia.440100209 PG 5 WC Neurosciences SC Neurosciences & Neurology GA MU209 UT WOS:A1994MU20900008 PM 8168868 ER PT J AU PETRAKOVA, E GLAUDEMANS, CPJ AF PETRAKOVA, E GLAUDEMANS, CPJ TI SYNTHESIS OF METHYL ALPHA-ISOMALTO-OLIGOSACCHARIDES SPECIFICALLY DEOXYGENATED AT POSITION 2 OF THE TERMINAL GLYCOPYRANOSYL UNIT SO GLYCOCONJUGATE JOURNAL LA English DT Article DE METHYL ALPHA-ISOMALTO-OLIGOSACCHARIDES; TERT-BUTYL(DIMETHYL) SILYL DONOR; 2-DEOXY-ALPHA-D-ARABINO-HEXOPYRANOSYL ID ACID RELATED-COMPOUNDS; STEREOSELECTIVE SYNTHESIS; ANTHRACYCLINE OLIGOSACCHARIDES; EFFICIENT DEOXYGENATION; SECONDARY ALCOHOLS; GENERAL PROCEDURE; CANCER-THERAPY; 2'-DEOXYNUCLEOSIDES; RIBONUCLEOSIDES; GLYCOSIDATION AB Methyl alpha-isomaltoside and methyl alpha-isomaltotrioside specifically deoxygenated at position C-2 of the terminal glucopyranosyl unit were synthesized by trimethylsilyltriflate-mediated condensation of 3,4,6-tri-O-benzoyl-1-O-tert-butyl(dimethyl)silyl-2-deoxy-beta-D-arabino-hexopyranose with suitably blocked derivatives of methyl alpha-D-glucopyranoside and methyl alpha-isomaltoside, respectively. RP PETRAKOVA, E (reprint author), NIDDKD,BETHESDA,MD 20892, USA. NR 28 TC 8 Z9 8 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0282-0080 J9 GLYCOCONJUGATE J JI Glycoconjugate J. PD FEB PY 1994 VL 11 IS 1 BP 17 EP 22 DI 10.1007/BF00732428 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MY256 UT WOS:A1994MY25600004 PM 8193549 ER PT J AU WILCOX, ER FEX, J AF WILCOX, ER FEX, J TI CONSTRUCTION OF A CDNA LIBRARY FROM MICRODISSECTED GUINEA-PIG CRISTA-AMPULLARIS SO HEARING RESEARCH LA English DT Article DE CRISTA AMPULLARIS; GUINEA PIG; MOLECULAR BIOLOGY; CLONING ID ORGAN; CORTI AB Poly(A) RNA was isolated from microdissected guinea pig crista ampullaris epithelium and converted into cDNA with RNase H- murine leukemia virus reverse transcriptase. After size fractionation, the cDNA was directionally ligated into the vector pSPORT 1 and the plasmids electroporated into E. coli. The library was found to have 1.6 x 10(7) independent colonies with 5% of the colonies lacking an insert. Thirty randomly selected colonies were checked for inserts and the average insert size was 833 base pairs with a range of 400 to 2300 base pairs. The library was screened with a beta-actin guinea pig cDNA probe and 0.16% of the colonies contained an insert hybridizing to the probe: RP WILCOX, ER (reprint author), NIDOCD,MOLEC BIOL LAB,BLDG 36,ROOM 5D-08,BETHESDA,MD 20892, USA. NR 8 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD FEB PY 1994 VL 73 IS 1 BP 65 EP 66 DI 10.1016/0378-5955(94)90283-6 PG 2 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA MV541 UT WOS:A1994MV54100007 PM 8157507 ER PT J AU FRIEDMAN, MA AF FRIEDMAN, MA TI NEW DIRECTIONS FOR BREAST-CANCER THERAPEUTIC RESEARCH SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID PHASE-II; TAXOL; DRUG RP FRIEDMAN, MA (reprint author), NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,EXECUT PLAZA N,RM 742,BETHESDA,MD 20892, USA. NR 18 TC 6 Z9 6 U1 0 U2 0 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 FEB PY 1994 VL 8 IS 1 BP 113 EP 119 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA MW742 UT WOS:A1994MW74200008 PM 8150774 ER PT J AU ARBUCK, SG DORR, A FRIEDMAN, MA AF ARBUCK, SG DORR, A FRIEDMAN, MA TI PACLITAXEL (TAXOL) IN BREAST-CANCER SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID HAMSTER OVARY CELLS; MICROTUBULE-ASSOCIATED PROTEINS; CYTO-TOXICITY; PHASE-I; ANTITUMOR AGENTS; TUBULIN; RESISTANCE; TAXANES; MUTANTS; INVIVO RP ARBUCK, SG (reprint author), NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,INVEST DRUG BRANCH,BETHESDA,MD 20892, USA. NR 64 TC 33 Z9 33 U1 0 U2 2 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 FEB PY 1994 VL 8 IS 1 BP 121 EP 140 PG 20 WC Oncology; Hematology SC Oncology; Hematology GA MW742 UT WOS:A1994MW74200009 PM 7908664 ER PT J AU WEISS, P ASHWELL, G MORELL, AG STOCKERT, RJ AF WEISS, P ASHWELL, G MORELL, AG STOCKERT, RJ TI MODULATION OF THE ASIALOGLYCOPROTEIN RECEPTOR IN HUMAN HEPATOMA-CELLS - EFFECT OF GLUCOSE SO HEPATOLOGY LA English DT Article ID LIGAND-INDUCED MODULATION; MEDIATED ENDOCYTOSIS; RAT HEPATOCYTES; SURFACE; GLUCOKINASE; PROTEINS; VANADATE; BIOTIN AB The hepatic receptor for asialoglycoproteins was found to be modulated by the glucose concentration in the medium of the human hepatoma cell line HepG2. The surface binding of asialoorosomucoid, a well-documented ligand for this receptor, increased from 20 ng/mg of cellular protein to about 40 ng/mg as the glucose concentration was increased from 10 to 50 mg/dl. The up-modulating effect of glucose was mimicked by pyruvate, a product of glucose metabolism, and abolished by both 2-deoxyglucose, an inhibitor of glucose metabolism, and by cycloheximide, an inhibitor of protein synthesis. Scatchard plot analysis indicated a rise in the number of binding sites and a twofold increase in binding affinity. In contrast, the binding of antibody remained unchanged with respect to alterations in glucose concentration, an indication that the actual number of receptors remained constant in face of an increased number of binding sites. Specificity of the glucose effect was shown by the binding of insulin and transferrin to their respective receptors, which was unaffected by the high glucose concentration that increased asialoorosomucoid binding. The repression of receptor binding seen with cells grown in biotin-deprived medium was reversed by increasing the glucose concentration of the medium. In this case, binding was restored to a level sixfold to sevenfold higher than that of the control cells grown in dialyzed serum. The stimulatory effect of glucose was shown to be independent of and significantly greater than that of cyclic GMP, a known regulator of receptor expression of biotin-deficient HepG2 cells. These results suggest that increasing glucose concentrations effect an activation of either silent or nonfunctional receptors or increase the stoichiometry of ligand binding per receptor complex. The data provided here are interpreted as suggesting a potential role of glucose in maintaining hepatic homeostasis through regulation of the asialoglycoprotein receptor. C1 ALBERT EINSTEIN COLL MED,LIVER RES CTR,DEPT MED,BRONX,NY 10461. ALBERT EINSTEIN COLL MED,LIVER RES CTR,DEPT BIOCHEM,BRONX,NY 10461. RP WEISS, P (reprint author), NIDDKD,BLDG 10,ROOM 9N-105,BETHESDA,MD 20892, USA. FU NIDDK NIH HHS [DK 32972, DK 17702] NR 25 TC 9 Z9 9 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 1994 VL 19 IS 2 BP 432 EP 439 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA MU618 UT WOS:A1994MU61800022 PM 8294100 ER PT J AU LUSTER, MI GERMOLEC, DR YOSHIDA, T KAYAMA, F THOMPSON, M AF LUSTER, MI GERMOLEC, DR YOSHIDA, T KAYAMA, F THOMPSON, M TI ENDOTOXIN-INDUCED CYTOKINE GENE-EXPRESSION AND EXCRETION IN THE LIVER SO HEPATOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; MESSENGER-RNA; INVIVO; CACHECTIN; INTERLEUKIN-1; RESISTANCE; MECHANISMS; IDENTITY; ALPHA; CELLS AB Peptide mediators, including tumor necrosis factor-alpha, interleukin 1 and interleukin-6, are associated with many chronic inflammatory diseases and septic shock. As such, considerable information has been collected by means of study of cytokine secretion from isolated cells or plasma cytokines during septic shock or inflammatory disorders. In this investigation, we used semiquantitative polymerase chain reaction analysis and a recently developed liver slice model to examine the characteristics of cytokine profiles that occur in the liver, the main organ involved in endotoxemia, after lipopolysaccharide challenge. Tumor necrosis factor-alpha, interleukin-1 alpha, and interleukin-6 were rapidly secreted after in vivo LPS exposure or when added in vitro to rodent or human liver slice samples. This increase was associated with increased cytokine-specific mRNA transcripts. Kinetic analysis revealed that most tumor necrosis factor-alpha is released from the liver within 1 hr of lipopolysaccharide challenge, whereas interleukin-1 alpha and interleukin-6 continued to be produced for the entire culture period. Addition of monoclonal antibodies against tumor necrosis factor-alpha or interleukin-1 alpha to the culture partly inhibited interleukin-6 secretion, indicating that interleukin-1 alpha and tumor necrosis factor-alpha help mediate and sustain interleukin-6 synthesis. Depletion of hepatic sinusoidal macrophages (Kupffer cells) by a liposome-mediated macrophage ''suicide'' technique indicated that almost all of the secreted interleukin-la and tumor necrosis factor-alpha originate from these cells, whereas interleukin-6 secretion might also include other cell types. This study supports and extends previous findings and allows for a more rational approach to developing effective therapies against chronic inflammatory diseases and septic shock. C1 NIEHS, MOLEC PATHOL LAB, RES TRIANGLE PK, NC 27709 USA. TOKAI UNIV, SCH MED, DEPT ENVIRONM HLTH, ISEHARA, KANAGAWA 25911, JAPAN. UNIV OCCUPAT & ENVIRONM HLTH, DEPT ENVIRONM HLTH, ORIO KITAKYUSHU 887, JAPAN. RP LUSTER, MI (reprint author), NIEHS, ENVIRONM IMMUNOL & NEUROBIOL SECT, MD C1-04, SOUTH CAMPUS, RES TRIANGLE PK, NC 27709 USA. NR 32 TC 183 Z9 192 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 1994 VL 19 IS 2 BP 480 EP 488 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA MU618 UT WOS:A1994MU61800028 PM 8294104 ER PT J AU JANINI, GM ISSAQ, HJ LUKSZO, J AF JANINI, GM ISSAQ, HJ LUKSZO, J TI DETERMINATION OF THE PURITY OF SYNTHETIC PEPTIDES BY CAPILLARY ELECTROPHORESIS, HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY, AND LASER-DESORPTION MASS-SPECTROMETRY SO HRC-JOURNAL OF HIGH RESOLUTION CHROMATOGRAPHY LA English DT Note DE HPLC; CAPILLARY ELECTROPHORESIS (CE); LASER DESORPTION MASS SPECTROMETRY; SYNTHETIC PEPTIDES; PURITY DETERMINATION C1 NIAID,BIOL RESOURCES BRANCH,FREDERICK,MD 21702. RP JANINI, GM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702, USA. NR 5 TC 6 Z9 6 U1 0 U2 1 PU DR ALFRED HUTHIG VERLAG GMBH PI HEIDELBERG 1 PA POSTFACH 102869, W-69018 HEIDELBERG 1, GERMANY SN 0935-6304 J9 HRC-J HIGH RES CHROM JI HRC-J. High Resolut. Chromatogr. PD FEB PY 1994 VL 17 IS 2 BP 102 EP 103 PG 2 WC Chemistry, Analytical SC Chemistry GA NA165 UT WOS:A1994NA16500010 ER PT J AU BHAT, NK ROMANOSPICA, V GEORGIOU, P CHEN, SL KUI, PG SUZUKI, H AF BHAT, NK ROMANOSPICA, V GEORGIOU, P CHEN, SL KUI, PG SUZUKI, H TI EPITOPE MAPPING OF HUMAN ETS1 MONOCLONAL-ANTIBODY SO HYBRIDOMA LA English DT Article ID SEQUENCE-SPECIFIC BINDING; LONG TERMINAL REPEAT; DNA-BINDING; C-ETS; C-ETS-1 PROTOONCOGENE; GENE FAMILY; PROTO-ONCOGENE; EXPRESSION; PHOSPHORYLATION; IDENTIFICATION AB The epitope for E44 monoclonal antibody (mAb) was mapped using mutated ETS1 proteins lacking different carboxy-terminal regions and by the employment of synthetic oligopeptides spanning the epitope region. This epitope lies around Arg211 of the human ETS1 protein since substitution of Arg211 by Gln211 in the epitope region results in the loss of recognition of the mouse ETS1 protein by E44 mAb. Substitution of Leu214 by valine214 in the epitope region (as is found in the chicken ETS1 and viral Ets proteins) does not alter the capacity of the E44 mAb to recognize this antigen. Taken together, these results suggest that a specific ionic interaction is able to play a pivotal role in the recognition of the ETS1 protein by the E44 mAb. C1 PROGRAM RESOURCES INC,DYNCORP,FREDERICK,MD 21702. RP BHAT, NK (reprint author), NCI,MOLEC ONCOL LAB,POB B,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 50 TC 5 Z9 5 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 FEB PY 1994 VL 13 IS 1 BP 1 EP 8 DI 10.1089/hyb.1994.13.1 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA ND400 UT WOS:A1994ND40000001 PM 7515374 ER PT J AU SOWERS, JR CUTLER, JA DONATO, K EASTMAN, RC FALKNER, B HORAN, MJ HSUEH, WA HYMAN, B REED, JW ROCCELLA, EJ SAVAGE, PJ SIWEK, J TUCK, ML WEINBERGER, MH WILLIAMS, G OBARZANEK, E AMES, MV ANDERSON, DE BRITO, GT AF SOWERS, JR CUTLER, JA DONATO, K EASTMAN, RC FALKNER, B HORAN, MJ HSUEH, WA HYMAN, B REED, JW ROCCELLA, EJ SAVAGE, PJ SIWEK, J TUCK, ML WEINBERGER, MH WILLIAMS, G OBARZANEK, E AMES, MV ANDERSON, DE BRITO, GT TI NATIONAL-HIGH-BLOOD-PRESSURE-EDUCATION-PROGRAM WORKING GROUP-REPORT ON HYPERTENSION IN DIABETES SO HYPERTENSION LA English DT Review DE DIABETES MELLITUS; HYPERTENSION, RENOVASCULAR; ANTIHYPERTENSIVE AGENTS ID INSULIN RESISTANCE; RISK-FACTORS; SEXUAL DYSFUNCTION; PLASMA-LIPOPROTEINS; WEIGHT-REDUCTION; HEART-DISEASE; MELLITUS; HYPERINSULINEMIA; MANAGEMENT; GLUCOSE AB Hypertension and diabetes mellitus are interrelated diseases that, if untreated, strongly predispose to atherosclerotic cardiovascular disease and renal disease. More than 3 million Americans have both hypertension and diabetes, which are particularly prevalent in the socioeconomically disadvantaged. Hypertension contributes substantially to morbidity and mortality in people with diabetes. This report is an update of the 1987 working group report on hypertension and diabetes and includes important new information on the management of hypertension in people with diabetes. Although treatment of hypertension in most people with diabetes does not differ from that in people who do not have diabetes, this report outlines some special considerations relevant to the presence of both diseases. Lifestyle modification is considered as an initial treatment modality or as an adjunct to pharmacologic measures. This report also includes a discussion of the treatment of hypertension and diabetes in children, an expanded review of sexual dysfunction, and an increased emphasis on the effect of hypertension and diabetes on target organs. A treatment algorithm represents a practical guideline for the physician. Since the previous report, there has been an increased awareness, through clinical trials and pharmacologic research, of the importance of flexibility in the use of antihypertensive drugs as well as a refinement of nonpharmacologic approaches in treating people with both hypertension and diabetes. C1 NHLBI,NATL HIGH BLOOD PRESSURE EDUC PROGRAM,BETHESDA,MD 20892. WAYNE STATE UNIV,DIV ENDOCRINOL METAB & HYPERTENS,DETROIT,MI. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. NHLBI,OFF PREVENT EDUC & CONTROL,BETHESDA,MD. NIDDKD,DIV DIABET ENDOCRINOL & METAB DIS,BETHESDA,MD. MED COLL PENN,PHILADELPHIA,PA. NHLBI,DIV HEART & VASC DIS,BETHESDA,MD. UNIV SO CALIF,LOS ANGELES CTY MED CTR,DIV DIABET HYPERTENS & NUTR,LOS ANGELES,CA. BAYLOR COLL MED,DEPT MED & OPHTHALMOL,HOUSTON,TX. MOREHOUSE SCH MED,ATLANTA,GA. GEORGETOWN UNIV,SCH MED,DEPT COMMUNITY & FAMILY MED,DIV FAMILY MED,WASHINGTON,DC. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. VET ADM MED CTR,SEPULVEDA,CA. INDIANA UNIV,SCH MED,INDIANAPOLIS,IN. INDIANA UNIV,HYPERTENS RES CTR,INDIANAPOLIS,IN. HARVARD UNIV,SCH MED,BOSTON,MA. BRIGHAM & WOMENS HOSP,DIV ENDOCRINE HYPERTENS,BOSTON,MA 02115. ROW SCI INC,ROCKVILLE,MD. UNIV RES CORP,BETHESDA,MD. NR 117 TC 184 Z9 191 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD FEB PY 1994 VL 23 IS 2 BP 145 EP 158 PG 14 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MV703 UT WOS:A1994MV70300001 ER PT J AU JACKSON, SH MALECH, HL KOZAK, CA LOMAX, KJ GALLIN, JI HOLLAND, SM AF JACKSON, SH MALECH, HL KOZAK, CA LOMAX, KJ GALLIN, JI HOLLAND, SM TI CLONING AND FUNCTIONAL EXPRESSION OF THE MOUSE HOMOLOG OF P47(PHOX) SO IMMUNOGENETICS LA English DT Note ID CHRONIC GRANULOMATOUS-DISEASE; NADPH OXIDASE C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. VET AFFAIRS MED CTR,WHITE RIVER JCT,VT 05009. NR 19 TC 26 Z9 28 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD FEB PY 1994 VL 39 IS 4 BP 272 EP 275 PG 4 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA MY369 UT WOS:A1994MY36900007 PM 8119734 ER PT J AU HAMAWY, MM MERGENHAGEN, SE SIRAGANIAN, RP AF HAMAWY, MM MERGENHAGEN, SE SIRAGANIAN, RP TI ADHESION MOLECULES AS REGULATORS OF MAST-CELL AND BASOPHIL FUNCTION SO IMMUNOLOGY TODAY LA English DT Article ID ENDOTHELIAL-CELLS; HISTAMINE-RELEASE; RBL-2H3 CELLS; FIBROBLASTS; EXPRESSION; ADHERENCE; NEUTROPHILS; RECEPTORS; LAMININ; INVITRO AB Basophils and mast cells play a role both in immediate allergic reactions and in inflammation. Both types of cells have surface adhesion receptors that can mediate binding to other cells and to extracellular matrix glycoproteins. Here Majed Hamawy and colleagues discuss the importance of these adhesion molecules in regulating basophil and mast-cell functions. RP HAMAWY, MM (reprint author), NIDR,IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 47 TC 82 Z9 82 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD FEB PY 1994 VL 15 IS 2 BP 62 EP 66 DI 10.1016/0167-5699(94)90135-X PG 5 WC Immunology SC Immunology GA MV632 UT WOS:A1994MV63200006 PM 8155264 ER PT J AU GORDON, VM LEPPLA, SH AF GORDON, VM LEPPLA, SH TI PROTEOLYTIC ACTIVATION OF BACTERIAL TOXINS - ROLE OF BACTERIAL AND HOST-CELL PROTEASES SO INFECTION AND IMMUNITY LA English DT Review ID PSEUDOMONAS EXOTOXIN-A; ANTHRACIS PROTECTIVE ANTIGEN; DIPHTHERIA-TOXIN; TETANUS TOXIN; BOTULINUM NEUROTOXIN; ESCHERICHIA-COLI; SHIGA TOXIN; PROCESSING ENDOPROTEASES; LIMITED PROTEOLYSIS; ADENYLATE-CYCLASE C1 NIDR,MICROBIAL ECOL LAB,BETHESDA,MD 20892. NR 99 TC 83 Z9 84 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD FEB PY 1994 VL 62 IS 2 BP 333 EP 340 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA MR841 UT WOS:A1994MR84100001 PM 8300195 ER PT J AU GINSBERG, HS PRINCE, GA AF GINSBERG, HS PRINCE, GA TI THE MOLECULAR-BASIS OF ADENOVIRUS PATHOGENESIS SO INFECTIOUS AGENTS AND DISEASE-REVIEWS ISSUES AND COMMENTARY LA English DT Review DE EARLY GENE EXPRESSION; E3 19-KDA GLYCOPROTEIN; E3 14.7-KDA GLYCOPROTEIN; TUMOR NECROSIS FACTOR-ALPHA; MHC CLASS-I; CYTOTOXIC T-CELL RESPONSE ID CELL-SURFACE EXPRESSION; CLASS-I ANTIGENS; TYPE-5 ADENOVIRUS; MHC ANTIGENS; COTTON RATS; PROTEIN; PNEUMONIA; MUTANTS; MODEL; INFECTION AB The pathology of type 5 (Ad5) pneumonia in Sigmodon hispidus cotton rats is closely similar to that in humans. Virus replicates in bronchiolar epithelial cells, but in situ hybridization shows early gene expression in macrophage/monocytes in alveoli and hilar lymph nodes. Only early gene expression is required to produce the pathology of which there is an ''early'' and a ''late'' phase. The early region 3 (E3), which does not function in viral replication, plays an important role in the natural history of at least the subgroup C adenoviruses (types 1, 2, 5, 6), which produce latent infections in host-infected lymphocytes: The 19-kDa glycoprotein markedly reduces the transport of the class I MHC to the surface of infected cells and, therefore, the attack of cytotoxic T cells, which could eliminate infected cells. When this gene is mutated, the late-phase inflammatory response to infection is markedly increased. The E3 14.7-kDa protein reduces the presence of polymorphonuclear leukocytes in the early-phase pathological inflammatory exudate. The E1B 55-kDa is essential to effect the late phase, and when its gene is mutated, the inflammation is greatly reduced although viral replication is not affected. Because only early genes are required to induce the complete pathogenesis of adenovirus infection in cotton rats, it is possible to produce the same pneumonia in lungs of mice in which only adenovirus early genes are expressed. In the unique mouse model, it was possible to demonstrate that tumor necrosis factor (TNF)-alpha, interleukin-1, (IL-1), and IL-6 cytokines are elaborated during the first 2 to 3 days after infection, but only TNF-alpha plays a major role in the early phase of pathogenesis. In nude mice, the late inflammatory response does not appear, indicating that it primarily consists of T cells. Steroids almost completely eliminate the pneumonic inflammatory response to infection. C1 COLUMBIA UNIV COLL PHYS & SURG,DEPT MICROBIOL,NEW YORK,NY 10032. COLUMBIA UNIV COLL PHYS & SURG,DEPT MED,NEW YORK,NY 10032. RP GINSBERG, HS (reprint author), NIAID,INFECT DIS LAB,TWIN BROOK 2,12441 PARK LAWN DR,ROCKVILLE,MD 20852, USA. FU NIAID NIH HHS [AI-12052] NR 40 TC 43 Z9 44 U1 0 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1056-2044 J9 INFECT AGENT DIS JI Infect. Agents Dis.-Rev. Issues Comment. PD FEB PY 1994 VL 3 IS 1 BP 1 EP 8 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA NZ494 UT WOS:A1994NZ49400001 PM 7952924 ER PT J AU KUBO, M KINCAID, RL WEBB, DR RANSOM, JT AF KUBO, M KINCAID, RL WEBB, DR RANSOM, JT TI THE CA2+ CALMODULIN-ACTIVATED, PHOSPHOPROTEIN PHOSPHATASE CALCINEURIN IS SUFFICIENT FOR POSITIVE TRANSCRIPTIONAL REGULATION OF THE MOUSE IL-4 GENE SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE BINDING MOTIF; LUCIFERASE; NUCLEAR BINDING PROTEIN; PROMOTER; REGULATORY ELEMENT; T-CELL RECEPTOR ID LYMPHOCYTE-T ACTIVATION; STIMULATORY FACTOR-I; CYCLOSPORINE-A; B-CELL; MESSENGER-RNA; CROSS-LINKAGE; FC-EPSILON; INTERLEUKIN-4; EXPRESSION; FK-506 AB We have studied the TCR mediated signal transduction pathways involved in transcriptional regulation of the mouse IL-4 gene. The sequences extending from base pair -766 to + 63 of the IL-4 gene were inserted upstream of a luciferase indicator gene. Transcriptional activity was observed when the construct, [pIL-4(- 766)], was transfected into either the IL-4 producing cell line, EL-4, or the IL-4 non-producing T cell hybridoma, 68-41, but not in the L929 fibroblast cell line. By analysis of deletion mutants of pIL-4(- 766), we identified a transcriptional regulatory element that is tightly associated with a signal coming from the TCR and which controls inducible activation of the IL-4 promoter. By analysis of deletion mutants of pIL-4(- 766), this latter element was found between base pairs - 147 to - 17. Electrophoretic mobility shift assays indicated that expression of a nuclear binding protein with binding sites between base pairs - 84 and - 55 could be induced. By competition and mutation analysis, the binding motif of this protein was determined to be AAAATTTTCC. Stimulation with ionomycin alone was sufficient to induce activity in pIL-4(- 766). Cyclosporin A inhibited both the IL-4 promoter activity and activation of the inducible nuclear protein. Transient over-expression of a constitutively active form of the Ca2+/Calmodulin-regulated protein phosphatase, calcineurin was sufficient to cause activation of pIL-4(- 766) without any additional stimulus. These results indicate that the signaling requirements for activation of upstream positive regulatory elements of the IL-4 gene are distinct from those of the IL-2 gene. Ca2+ Mobilization is sufficient to activate the IL-4 promoter, whereas IL-2 gene transcription requires both Ca2+ mobilization and protein kinase C activation. C1 SYNTEX DISCOVERY RES,DEPT INFLAMMAT BIOL & IMMUNOL,S3-6,PALO ALTO,CA 94304. NATL INST ALCOHOL ABUSE & ALCOHOL,MOLEC & CELLULAR NEUROBIOL LAB,IMMUNOL SECT,ROCKVILLE,MD 20852. NR 40 TC 61 Z9 61 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD FEB PY 1994 VL 6 IS 2 BP 179 EP 188 DI 10.1093/intimm/6.2.179 PG 10 WC Immunology SC Immunology GA MW888 UT WOS:A1994MW88800002 PM 8155595 ER PT J AU STEVENS, RG GRAUBARD, BI MICOZZI, MS NERIISHI, K BLUMBERG, BS AF STEVENS, RG GRAUBARD, BI MICOZZI, MS NERIISHI, K BLUMBERG, BS TI MODERATE ELEVATION OF BODY IRON LEVEL AND INCREASED RISK OF CANCER OCCURRENCE AND DEATH SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID SERUM FERRITIN; STOMACH-CANCER; BLOOD-DONORS; HEMOCHROMATOSIS; PROLIFERATION; DEFICIENCY; MORTALITY; CELLS; MICE; CARCINOGENESIS AB The purpose of the study was to address the hypothesis that elevated body iron increases the risk of cancer occurrence and death, and to determine the dose response. Subjects were 3,287 men and 5,269 women participating in the first National Health and Nutrition Examination Survey who had a transferrin saturation determination at enrollment (1971-1975), who remained alive and cancer-free for at least 4 years, and who were followed to 1988 for cancer outcome. Among 379 men who developed cancer over the study period, the mean transferrin saturation at enrollment was 32.1% whereas among 2,908 who remained cancer-free it was 30.7%; the difference for mortality was 32.3% among 233 deaths vs. 30.8% among 3,054 men not dying of cancer. The mean differences among women were not significant. The mean differences in TIBC and serum iron among men were consistent with the findings for transferrin saturation, and all 3 differences were stable over time when examined by years since blood test. Men and women were divided into 5 groups on the basis of baseline transferrin saturation: 0 to 30%, 30-40%, 40-50%, 50-60%, and 60% and higher. Nineteen percent of men had a baseline transferrin saturation above 40% (the last 3 groups), whereas only 10 percent of women had transferrin saturation above 40%. For men and women combined, risk of cancer occurrence in each group relative to the first was 1.0, 0.95, 1.16, 1.38 and 1.81; for mortality the relative risks were 1.0, 0.96, 1.22, 1.29 and 1.73. There is evidence, in this cohort, of elevated cancer risk in those with moderately elevated iron level. This pattern was seen in women as well as in men. (C) 1994 Wiley-Liss, Inc. C1 NCI, DIV CANC ETIOL, BIOMETRY BRANCH, BETHESDA, MD 20892 USA. NATL MUSEUM HLTH & MED, ARMED FORCES INST PATHOL, WASHINGTON, DC 20306 USA. RADIAT EFFECTS RES FDN, HIROSHIMA, JAPAN. FOX CHASE CANC CTR, PHILADELPHIA, PA USA. UNIV OXFORD BALLIOL COLL, OXFORD OX1 3BJ, ENGLAND. RP STEVENS, RG (reprint author), PACIFIC NW LAB, CTR LIFE SCI, RICHLAND, WA 99352 USA. FU NCI NIH HHS [CA-40737, CA-06927]; NCRR NIH HHS [RR-05895] NR 46 TC 196 Z9 199 U1 1 U2 3 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 FEB 1 PY 1994 VL 56 IS 3 BP 364 EP 369 DI 10.1002/ijc.2910560312 PG 6 WC Oncology SC Oncology GA MU556 UT WOS:A1994MU55600011 PM 8314323 ER PT J AU ZAWIA, NH EVERS, LB HARRY, GJ AF ZAWIA, NH EVERS, LB HARRY, GJ TI DEVELOPMENTAL PROFILES OF ORNITHINE DECARBOXYLASE ACTIVITY IN THE HIPPOCAMPUS, NEOCORTEX AND CEREBELLUM - MODULATION FOLLOWING LEAD-EXPOSURE SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE ODC; PB; HIPPOCAMPUS; NEOCORTEX; CEREBELLUM; DEVELOPMENT ID DEVELOPING RAT; NUCLEIC-ACIDS; BRAIN; NEUROTOXICITY; MECHANISMS; METHYLMERCURY; POLYAMINES; CHILDREN; REGIONS AB Ornithine decarboxylase (ODC) is a growth-associated enzyme which is critical for cell growth and transformation. ODC activity follows a specific ontogenetic pattern of activity in distinct brain regions according to their developmental stage. Perturbations in the pattern of ODC activity have been associated with brain damage including arrested cerebral growth. Modulations in the pattern of ODC activity were examined in the hippocampus, neocortex and cerebellum of neonatal rats (PND 3, 6, 9, 15) exposed via the dam to 0.2% lead-acetate (pb(2+) prenatally (gestational day 13 to birth), postnatally (PND 1-15) or perinatally (gestational day 13 to PND 15). Prenatal exposure to Pb2+ perturbed the profile of ODC activity in all three brain regions examined, while postnatal exposure to Pb2+ resulted in prolonged stimulations of OD C activity in the cerebellum. Following prenatal exposure, these effects were manifested as a stimulation of ODC activity in the hippocampus, a repression of activity in the neocortex and a combination of these effects in the cerebellum. Perinatal exposure to Pb2+ transiently modulated the pattern of ODC activity similarly in all three brain regions, in a characteristic manner irrespective of their developmental stage. These Pb2+-induced modulations of ODC activity suggest that polyamine-dependent processes may play a significant role in the manifestation of Pb2+-induced neurotoxicity dependent upon developmental factors at specific exposure periods. C1 NIEHS,DIV INTRAMURAL RES,INTEGRAT BIOL LAB,RES TRIANGLE PK,NC 27707. NR 39 TC 9 Z9 9 U1 1 U2 1 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 FEB PY 1994 VL 12 IS 1 BP 25 EP 30 DI 10.1016/0736-5748(94)90092-2 PG 6 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA NA231 UT WOS:A1994NA23100003 PM 8010157 ER PT J AU EGWUAGU, CE SZTEIN, J CHAN, CC REID, W MAHDI, R NUSSENBLATT, RB CHEPELINSKY, AB AF EGWUAGU, CE SZTEIN, J CHAN, CC REID, W MAHDI, R NUSSENBLATT, RB CHEPELINSKY, AB TI ECTOPIC EXPRESSION OF GAMMA-INTERFERON IN THE EYES OF TRANSGENIC MICE INDUCES OCULAR PATHOLOGY AND MHC CLASS-II GENE-EXPRESSION SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE GAMMA-IFN; INTERFERON; TRANSGENIC MICE; LENS DIFFERENTIATION; EYE DEVELOPMENT; MAJOR HISTOCOMPATIBILITY COMPLEX (MHC); CLASS II ID LENS-SPECIFIC EXPRESSION; A-CRYSTALLIN GENE; DNA-BINDING PROTEIN; HISTOCOMPATIBILITY ANTIGENS; COLLAGEN-SYNTHESIS; EPITHELIAL-CELLS; IMMUNE-RESPONSE; TENONS CAPSULE; GROWTH-FACTOR; HYBRID GENE AB Purpose. To direct the expression of gamma IFN to the eyes of transgenic mice as a means of investigating the possible role of this lymphokine in ocular pathogenesis. Methods. Transgenic mouse strains were generated by injection of a DNA fragment containing the murine alpha A-crystallin promoter fused to the coding sequence of murine gamma IFN gene. PCR and RT-PCR were used to screen for the presence of the transgene and mRNA analyses, respectively. Methacrylate-embedded eye sections were analyzed for morphology and cryosections for immunoperoxidase antibody staining. Results. The most notable effects of gamma IFN in these transgenic mice include cataract, microphthalmia, blepharophimosis, microphakia, impairment of lens fiber formation, arrest of retinal differentiation, serous retinal detachment with presence of macrophages in the subretinal space, persistent hyperplastic primary vitreous, and corneal vascularization. MHC class II mRNA levels were significantly increased in the transgenic eyes and MHC class II proteins were expressed in their cornea, iris, ciliary body, choroid, lens and RPE. C1 NEI,IMMUNOL LAB,BETHESDA,MD 20892. NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892. NEI,VET RES & RESOURCE SECT,BETHESDA,MD. RI Sztein, Jorge/B-7165-2012 NR 63 TC 40 Z9 41 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD FEB PY 1994 VL 35 IS 2 BP 332 EP 341 PG 10 WC Ophthalmology SC Ophthalmology GA MY957 UT WOS:A1994MY95700003 PM 8112978 ER PT J AU SHIKATA, A SUGIMOTO, T HOSOI, H SOTOZONO, Y SHIKATA, T SAWADA, T PARADA, LF AF SHIKATA, A SUGIMOTO, T HOSOI, H SOTOZONO, Y SHIKATA, T SAWADA, T PARADA, LF TI INCREASED EXPRESSION OF TRK PROTOONCOGENE BY GAMMA-INTERFERON IN HUMAN NEUROBLASTOMA SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Note DE GAMMA-INTERFERON; TRK; N-MYC; NEUROBLASTOMA ID HUMAN NEURO-BLASTOMA; NERVE GROWTH-FACTOR; SURFACE MEMBRANE-ANTIGENS; N-MYC; CELL-LINES; FACTOR RECEPTOR; PROTOONCOGENE PRODUCT; INVERSE RELATIONSHIP; GENE-EXPRESSION; CYCLIC-AMP AB Three human neuroblastoma cell lines were examined to determine the effect of recombinant gamma-interferon (IFN-gamma) treatment on the expression of trk proto-oncogene. Increased levels of trk proto-oncogene mRNA were observed in two neuroblastoma cell lines (KP-N-RT and KP-N-SI(FA)) after IFN-gamma treatment. The levels of trk mRNA increased with growth inhibition and morphological change in a time- and dose-dependent manner. The decreased level of N-myc mRNA after IFN-gamma treatment in KP-N-RT was inversely correlated with trk mRNA. Our results suggest that IFN-gamma can modulate the signal transduction of nerve growth factor in human neuroblastoma cells. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,MOLEC EMBRYOL SECT,FREDERICK,MD 21702. RP SHIKATA, A (reprint author), KYOTO PREFECTURAL UNIV MED,DEPT PEDIAT,KAMIGYO KU,465 KAJII CHO,KYOTO,KYOTO 602,JAPAN. RI Parada, luis/B-9400-2014 FU NCI NIH HHS [N01-CO-74101] NR 23 TC 9 Z9 9 U1 0 U2 0 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 FEB PY 1994 VL 85 IS 2 BP 122 EP 126 PG 5 WC Oncology SC Oncology GA MX615 UT WOS:A1994MX61500004 PM 8144393 ER PT J AU KRAEMER, KH AF KRAEMER, KH TI NUCLEOTIDE EXCISION-REPAIR GENES INVOLVED IN XERODERMA-PIGMENTOSUM SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Editorial Material ID CLONING; MUTATION; ERCC2 RP KRAEMER, KH (reprint author), NCI,MOLEC CARCINOGENESIS LAB,BLDG 37 ROOM 3E24,BETHESDA,MD 20892, USA. NR 22 TC 0 Z9 0 U1 1 U2 2 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 FEB PY 1994 VL 85 IS 2 BP COV2 EP COV2 PG 1 WC Oncology SC Oncology GA MX615 UT WOS:A1994MX61500001 ER PT J AU TARULLO, LB DEMULDER, EK MARTINEZ, PE RADKEYARROW, M AF TARULLO, LB DEMULDER, EK MARTINEZ, PE RADKEYARROW, M TI DIALOGS WITH PREADOLESCENTS AND ADOLESCENTS - MOTHER-CHILD INTERACTION PATTERNS IN AFFECTIVELY ILL AND WELL DYADS SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article ID MATERNAL DEPRESSION; PSYCHIATRIC-DISORDER; PARENTS; RISK; FAMILY; WOMEN; PERCEPTIONS; DIAGNOSES AB This study examined affective/communicative patterns in the interactions of unipolar, bipolar, and well mothers with their preadolescent and adolescent children. As part of a large longitudinal project, mother-child interaction was assessed for two siblings ages 8 to 11 and 12 to 16. Interactional difficulties were linked to both maternal affective illness and child problem status. preadolescent children appeared more comfortable/happy with well mothers than with affectively ill mothers. Mothers and their preadolescents were more critical/irritable with each other when the child had a psychiatric disorder. Gender differences were apparent, particularly in regard to mother's current psychiatric status. Interactions in adolescent-daughter dyads were more critical when mothers met criteria for a major depressive episode within the month. The results illuminate interactive processes through which psychopathology may be perpetuated in families. RP TARULLO, LB (reprint author), NIMH,BLDG 15-K,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 40 TC 22 Z9 22 U1 2 U2 2 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 FEB PY 1994 VL 22 IS 1 BP 33 EP 51 DI 10.1007/BF02169255 PG 19 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA MV441 UT WOS:A1994MV44100003 PM 8163774 ER PT J AU WIDIGER, TA COSTA, PT AF WIDIGER, TA COSTA, PT TI PERSONALITY AND PERSONALITY-DISORDERS SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Review ID DSM-III-R; 5-FACTOR MODEL; INTERNAL CONSISTENCY; EPIDEMIOLOGIC SURVEY; FACTORIAL STRUCTURE; UNITED-STATES; CLASSIFICATION; POPULATION; SCALES; MCMI AB The mental disorders that most clearly relate to personality are the personality disorders. The purpose of this article is to review the support for the hypothesis that the personality disorders of the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.; American Psychiatric Association, 1987) represent variants of normal personality traits. We focus in particular on the efforts to identify the dimensions of personality that may underlie the personality disorders. We then illustrate the relationship of personality to personality disorders using the five-factor model, discuss conceptual issues in relating normal and abnormal personality traits, and consider methodological issues that should be addressed in future research. C1 NIA,BALTIMORE,MD 21224. RP WIDIGER, TA (reprint author), UNIV KENTUCKY,DEPT PSYCHOL,115 KASTLE HALL,LEXINGTON,KY 40506, USA. OI Costa, Paul/0000-0003-4375-1712 NR 106 TC 202 Z9 204 U1 12 U2 23 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD FEB PY 1994 VL 103 IS 1 BP 78 EP 91 DI 10.1037//0021-843X.103.1.78 PG 14 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA MW752 UT WOS:A1994MW75200010 PM 8040485 ER PT J AU HERSHBERGER, SL LICHTENSTEIN, P KNOX, SS AF HERSHBERGER, SL LICHTENSTEIN, P KNOX, SS TI GENETIC AND ENVIRONMENTAL-INFLUENCES ON PERCEPTIONS OF ORGANIZATIONAL-CLIMATE SO JOURNAL OF APPLIED PSYCHOLOGY LA English DT Article ID TWINS REARED APART; JOB-SATISFACTION; FAMILY ENVIRONMENT; NEGATIVE AFFECT; LAST HALF; LIFE-SPAN; PERSONALITY; ATTITUDES; SCALES AB Genetic and environmental influences on perceptions of organizational climate were assessed by using a 4-group twin design. Data were obtained as part of the Swedish Adoption/Twin Study of Aging. The Work Environment Scale (WES) was used to evaluate perceptions of organizational climate. A measure of job satisfaction was also used to evaluate the effects of genes and environments on job attitudes. Maximum likelihood estimates of genetic and environmental influence suggested significant genetic effects for Supportive Climate-1 factor resulting from a factor analysis of the WES-but not for a second factor, Time Pressure. Significant environmental effects were found for both Supportive Climate and Time Pressure. Genetic effects were not significant for job satisfaction. The relevance of findings to organizational climate research and personnel selection are discussed. C1 PENN STATE UNIV,COLL HLTH & HUMAN DEV,UNIV PK,PA 16802. KAROLINSKA INST,INST ENVIRONM MED,S-10401 STOCKHOLM 60,SWEDEN. NHLBI,BETHESDA,MD 20892. FU NIA NIH HHS [AG-10175, AG-04563] NR 48 TC 34 Z9 34 U1 1 U2 11 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0021-9010 J9 J APPL PSYCHOL JI J. Appl. Psychol. PD FEB PY 1994 VL 79 IS 1 BP 24 EP 33 DI 10.1037//0021-9010.79.1.24 PG 10 WC Psychology, Applied; Management SC Psychology; Business & Economics GA MX052 UT WOS:A1994MX05200003 PM 8200871 ER PT J AU ANDERSON, LT ERNST, M AF ANDERSON, LT ERNST, M TI SELF-INJURY IN LESCH-NYHAN DISEASE SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article ID BEHAVIOR AB Parents of 40 patients with Lesch-Nyhan disease completed a questionnaire detailing developmental history, life course, management, medication, factors influencing variability and topography of self-injury. Several conclusions were reached. Characteristics: Biting was the predominant form, perhaps only because of the difficulty of preventing it. There was considerable variability in self-injury which was strongly related to stress rather than to operant influences. Even though patients could not inhibit self-injury they could predict it and request restraints. Aggression against others was as prevalent as self-injury. Management. Stress reduction, teeth extraction, and physical restraint were the most commonly used management techniques. Behavior modification was of limited efficacy. Benzodiazepines were the most commonly used medications for controlling self-injury. Outcome. The severity of self-injury did not change over years. Age of onset was a predictor of outcome. The earlier the age of onset the worse the self-injury eventually became. The discussion describes research strategies, suggests dimensions along which self-injury can be classified, and highlights behavior not commonly described in patients with Lesch-Nyhan disease. C1 NIMH,CEREBRAL METAB LAB,CLIN BRAIN IMAGING SECT,BETHESDA,MD 20892. RP ANDERSON, LT (reprint author), NYU MED CTR,DEPT PSYCHIAT,NEW YORK,NY 10016, USA. FU NIMH NIH HHS [1 T32MH-18915] NR 14 TC 92 Z9 92 U1 1 U2 6 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD FEB PY 1994 VL 24 IS 1 BP 67 EP 81 DI 10.1007/BF02172213 PG 15 WC Psychology, Developmental SC Psychology GA MY519 UT WOS:A1994MY51900005 PM 8188575 ER PT J AU WILLIAMSON, PR AF WILLIAMSON, PR TI BIOCHEMICAL AND MOLECULAR CHARACTERIZATION OF THE DIPHENOL OXIDASE OF CRYPTOCOCCUS-NEOFORMANS - IDENTIFICATION AS A LACCASE SO JOURNAL OF BACTERIOLOGY LA English DT Article ID SEQUENCE-ANALYSIS; ASCORBATE OXIDASE; BLUE OXIDASES; GENE; CERULOPLASMIN; PROTEINS; HOMOLOGY; CLONING; YEAST; CATECHOLAMINES AB Melanin production is a major virulence factor for Cryptococcus neoformans, an organism causing life-threatening infections in an estimated 10% of AIDS patients. In order to characterize the events involved in melanin synthesis, an enzyme having diphenol oxidase activity was purified and its gene was cloned. The enzyme was purified as a glycosylated 75-kDa protein which migrated at 66 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis after deglycosylation by endoglycosidase F. Substrate specificity resembled that of a laccase in that it oxidized multiple diphenolic and diamino compounds. Dopamine was shown by mass spectroscopy to be oxidized to decarboxy dopachrome, an intermediate of melanin synthesis. The enzyme contained 4.1 +/- 0.1 mol of copper per mol. It resembled a laccase in its absorbance spectrum, containing a peak at 610 nm and the shoulder at 320 nm, corresponding to the absorbance of a type I and type III copper, respectively. The cloned gene of C. neoformans laccase (CNLAC1) contained a single open reading frame encoding a polypeptide 624 amino acids in length. The encoded polypeptide contained a presumptive leader sequence, on the basis of its relative hydrophobicity and by comparison of the sequence to that of the N-terminal sequence of the purified enzyme. CNLAC1 also contained 14 introns ranging from 52 to 340 bases long. Transcriptional activity of CNLAC1 was found to be derepressed in the absence of glucose and to correspond to an increase in enzymatic activity. RP WILLIAMSON, PR (reprint author), NIAID,CLIN INVEST LAB,CLIN MYCOL SECT,BLDG 10,ROOM 11C304,BETHESDA,MD 20892, USA. NR 51 TC 243 Z9 254 U1 0 U2 3 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 FEB PY 1994 VL 176 IS 3 BP 656 EP 664 PG 9 WC Microbiology SC Microbiology GA MU151 UT WOS:A1994MU15100014 PM 8300520 ER PT J AU KARLS, RK JIN, DJ DONOHUE, TJ AF KARLS, RK JIN, DJ DONOHUE, TJ TI TRANSCRIPTION PROPERTIES OF RNA-POLYMERASE HOLOENZYMES ISOLATED FROM THE PURPLE NONSULFUR BACTERIUM RHODOBACTER-SPHAEROIDES (VOL 175, PG 7635, 1993) SO JOURNAL OF BACTERIOLOGY LA English DT Correction, Addition C1 NCI,BETHESDA,MD 20892. RP KARLS, RK (reprint author), UNIV WISCONSIN,DEPT BACTERIOL,MADISON,WI 53706, USA. NR 1 TC 0 Z9 0 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 FEB PY 1994 VL 176 IS 3 BP 938 EP 938 PG 1 WC Microbiology SC Microbiology GA MU151 UT WOS:A1994MU15100048 ER PT J AU ZHANG, CJ ROSENWALD, AG WILLINGHAM, MC SKUNTZ, S CLARK, J KAHN, RA AF ZHANG, CJ ROSENWALD, AG WILLINGHAM, MC SKUNTZ, S CLARK, J KAHN, RA TI EXPRESSION OF A DOMINANT ALLELE OF HUMAN ARF1 INHIBITS MEMBRANE TRAFFIC IN-VIVO SO JOURNAL OF CELL BIOLOGY LA English DT Article ID ADP-RIBOSYLATION FACTOR; GTP-BINDING-PROTEIN; BREFELDIN-A; ORGANELLE STRUCTURE; GUANINE-NUCLEOTIDE; ESCHERICHIA-COLI; GOLGI MEMBRANES; COATED VESICLES; BETA-COP; GS-ALPHA AB ADP-ribosylation factor (ARF) proteins and inhibitory peptides derived from ARFs have demonstrated activities in a number of in vitro assays that measure ER-to-Golgi and intra-Golgi transport and endosome fusion. To better understand the roles of ARF proteins in vivo, stable cell lines were obtained from normal rat kidney (NRK) cells transfected with either wild-type or a dominant activating allele ([Q71L]) of the human ARF1 gene under the control of the interferon-inducible mouse Mx1 promoter. Upon addition of interferon, expression of ARF1 proteins increased with a half-time of 7-8 h, as determined by immunoblot analysis. Induction of mutant ARF1, but not wild-type ARF1, led to an inhibition of protein secretion with kinetics similar to that observed for induction of protein expression. Examination of the Golgi apparatus and the ER by indirect immunofluorescence or transmission electron microscopy revealed that expression of low levels of mutant ARF1 protein correlated with a dramatic increase in vesiculation of the Golgi apparatus and expansion of the ER lumen, while expression of substantially higher levels of wild-type ARF1 had no discernible effect. Endocytosis was also inhibited by expression of mutant ARF1, but not by the wild-type protein. Finally, the expression of [Q71L]ARF1, but not wild-type ARF1, antagonized the actions of brefeldin A, as determined by the delayed loss of ARF and beta-COP from Golgi membranes and disruption of the Golgi apparatus. General models for the actions of ARF1 in membrane traffic events are discussed. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BIOL CHEM LAB,BLDG 37,ROOM 5D02,BETHESDA,MD 20892. MED UNIV S CAROLINA,DEPT PATHOL & LAB MED,CHARLESTON,SC 29425. NINCDS,VIRAL & MOLEC PATHOGENESIS LAB,BETHESDA,MD 20892. NR 47 TC 146 Z9 148 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD FEB PY 1994 VL 124 IS 3 BP 289 EP 300 DI 10.1083/jcb.124.3.289 PG 12 WC Cell Biology SC Cell Biology GA MT699 UT WOS:A1994MT69900006 PM 8294513 ER PT J AU MOLES, JP SCHILLER, JT TESNIERE, A LEIGH, IM GUILHOU, JJ BASSETSEGUIN, N AF MOLES, JP SCHILLER, JT TESNIERE, A LEIGH, IM GUILHOU, JJ BASSETSEGUIN, N TI ANALYSIS OF HPV16 E6 AND MUTANT P53-TRANSFECTED KERATINOCYTES IN RECONSTITUTED EPIDERMIS SUGGESTS THAT WILD-TYPE P53 INHIBITS CYTOKERATIN-19 EXPRESSION SO JOURNAL OF CELL SCIENCE LA English DT Article DE P53; HPV; KERATINOCYTE ID HUMAN PAPILLOMAVIRUS TYPE-16; BASAL-CELL CARCINOMA; GENE-PRODUCT; DIFFERENTIATION; MUTATIONS; TRANSCRIPTION; INVITRO; CANCER; IMMORTALIZATION; DEGRADATION AB Using a reconstituted skin culture model Ive have analysed the effects of oncogenic human papillomavirus (HPV) and mutant TP53 genes on the proliferation and differentiation of human keratinocytes. Immortal cell lines generated by transfection of early passage normal human keratinocytes with HPV16 E7 plus mutant human TP53 (KN #1), HPV16 E7/E6 (KN #2), or HPV16 E7 plus murine p53 (KN #3) were examined. KN #1 and KN #2 behaved identically, reconstructing a tumor-like epidermis characterized by the lack of differentiation and the presence of an aberrant epidermal architecture. In contrast, KN #3 reconstructed an epidermis that was more similar to that obtained with normal keratinocytes. KN #1 and KN #2 were further characterized by the inversion of the proliferative compartment and the abnormal expression of cytokeratin 19 (CK19). Because p53 function is reduced in these cells, either by heterocomplex formation between endogenous wild-type p53 and transfected mutant p53 or by E6-induced degradation of wild-type p53, we hypothesized that CK19 expression may be normally repressed by wild-type p53. This hypothesis was supported by the strict correlation observed between TP53 mutation and CK19 expression in a set of human skin tumors. CK19 was detected in all eight carcinomas containing a mutated TP53 gene but in none of the 16 carcinomas containing only wild-type TP53. These results illustrate the utility of the in vitro reconstituted skin model for investigating the consequences of genetic alterations in human keratinocytes. C1 IGM MONTPELLIER,DERMATOL MOLEC LAB,F-34033 MONTPELLIER,FRANCE. NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. LONDON HOSP,COLL MED,ICRF,SKIN TUMOUR LAB,LONDON,ENGLAND. NR 45 TC 14 Z9 15 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD FEB PY 1994 VL 107 BP 435 EP 441 PN 2 PG 7 WC Cell Biology SC Cell Biology GA MY783 UT WOS:A1994MY78300009 PM 7515894 ER PT J AU BUSS, F KENT, H STEWART, M BAILER, SM HANOVER, JA AF BUSS, F KENT, H STEWART, M BAILER, SM HANOVER, JA TI ROLE OF DIFFERENT DOMAINS IN THE SELF-ASSOCIATION OF RAT NUCLEOPORIN P62 SO JOURNAL OF CELL SCIENCE LA English DT Article DE NUCLEAR PORE; MACROMOLECULAR ASSEMBLY; STRUCTURE ID NUCLEAR-PORE COMPLEX; ESCHERICHIA-COLI; MONOCLONAL-ANTIBODIES; PARACRYSTAL FORMATION; PROTEIN; GLYCOPROTEIN; EXPRESSION; IDENTIFICATION; SEQUENCE; ROD AB We have expressed rat nucleoporin p62 cDNA in Escherichia coli to obtain material for structural and self-association studies. Electron microscopy and circular dichroism spectroscopy are consistent with a rod-shaped molecule with an a-helical coiled-coil domain at its C terminus and a cross-beta structure at its N terminus, separated by a threonine-rich linker, which has a less-defined secondary structure. Electron microscopy and the solubility properties of fragments produced using thrombin and CNBr digestion indicate that p62 molecules associate to form linear chains and that a small region near the C terminus is an important determinant of assembly. This association may have important consequences for pore structure and function; for example, one way p62 could associate would be to form rings in nuclear pores that could function like barrel hoops., C1 MRC,MOLEC BIOL LAB,CAMBRIDGE CB2 2QH,ENGLAND. NIH,BETHESDA,MD 20892. NR 43 TC 51 Z9 51 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD FEB PY 1994 VL 107 BP 631 EP 638 PN 2 PG 8 WC Cell Biology SC Cell Biology GA MY783 UT WOS:A1994MY78300027 PM 8207085 ER PT J AU STEVEN, AC STEINERT, PM AF STEVEN, AC STEINERT, PM TI PROTEIN-COMPOSITION OF CORNIFIED CELL ENVELOPES OF EPIDERMAL-KERATINOCYTES SO JOURNAL OF CELL SCIENCE LA English DT Article DE TRANSGLUTAMINASE; CELL ENVELOPE; KERATINOCYTE; TERMINAL DIFFERENTIATION; AMINO ACID COMPOSITION; APOPTOSIS ID CROSS-LINKED ENVELOPE; HUMAN LORICRIN GENE; ALPHA-KERATIN; TRANSGLUTAMINASE; MOUSE; DIFFERENTIATION; EXPRESSION; SUBSTRATE; FILAGGRIN; ACID AB Terminally differentiated mammalian epidermal cells are lined with a 15 nm thick layer of proteins cross-linked by isodipeptide and disulfide bonds, called the cornified cell envelope (CE). A number of proteins, including involucrin, loricrin, cystatin A, filaggrin, a cysteine-rich protein (CRP) and the 'small proline-rich' proteins (SPRRs) have been reported to be components of this complex, but little information has been obtained as to their relative abundances because the acute insolubility of the CEs has precluded direct methods of analysis. To address this question, we have determined the amino acid compositions of isolated CEs, and then meddled them in terms of linear combinations of the;candidate proteins. The results show that stratum corneum CEs have a loricrin content of 65-70% (w/w) in human, and 80-85% in mouse. In human epidermal CEs, the secondary contributors are filaggrin and CRP (each similar to 10%), with smaller amounts of involucrin, SPRR and cystatin A (2-5% each) also present. Mouse epidermal CEs have about the same amount of filaggrin and somewhat more SPRR, but only trace amounts of the other proteins. In marked contrast, the major constituents of the CEs of cultured keratinocytes induced to terminal differentiation in vitro are cystatin A, involucrin and CRP (each similar to 30%). No significant amount of loricrin was detected except in sloughed mouse cells, which represent a more advanced state of terminal differentiation than attached cells. These results demonstrate that the CEs of cultured cells are quite different from mature CEs from native epidermis, and further suggest that generation of the CE in vivo is a multi-stage process in which involucrin, SPRR, CRP and cystatin A are initially attached to the cell membrane, and are subsequently overlaid with a heavy deposition of loricrin together with some filaggrin. Our data suggest that cultured CEs approximate only the first stage(s) of this process. C1 NIAMSD,SKIN BIOL BRANCH,BETHESDA,MD. RP STEVEN, AC (reprint author), NIAMSD,STRUCT BIOL LAB,BETHESDA,MD 20892, USA. NR 56 TC 176 Z9 178 U1 0 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD FEB PY 1994 VL 107 BP 693 EP 700 PN 2 PG 8 WC Cell Biology SC Cell Biology GA MY783 UT WOS:A1994MY78300033 PM 8207091 ER PT J AU ISHIGAMI, A ROTH, GS AF ISHIGAMI, A ROTH, GS TI AGE-RELATED-CHANGES IN DNA-SYNTHESIS STIMULATED BY EPINEPHRINE AND ISOPROTOTERENOL IN PRIMARY CULTURED RAT HEPATOCYTES SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID AFFINITY AGONIST BINDING; ADENYLATE-CYCLASE COMPLEX; EPIDERMAL GROWTH-FACTOR; MUSCARINIC RECEPTORS; SIGNAL TRANSDUCTION; ALZHEIMERS-DISEASE; SENESCENT RATS; PROTEIN; ADULT; GLYCOGENOLYSIS AB We examined epinephrine- and isoproterenol-stimulated DNA synthesis in primary cultured hepatocytes from 6-, 12-, and 24-month-old rats. Epinephrine-stimulated DNA synthesis in 6-month-old rat hepatocytes began after 20 h and reached a maximum at 50 h. Similarly, isoproterenol-stimulated DNA synthesis in 6-month-old rat hepatocytes began after 10 h and reached a maximum at 45 h. In contrast, both epinephrine- and isoprorerenol-stimulated DNA synthesis in 12- and 24-month-old rat hepatocytes were reduced approximately 40-60% and 80%, respectively, as compared to that at 6 months. Both epinephrine- and isoproterenol-stimulated DNA synthesis were strongly inhibited by the beta-adrenergic antagonist, propranolol, but not by the alpha(1)-adrenergic antagonist, prazosin, or the alpha(2)-adrenergic antagonist, yohimbine. However, in the presence of EGF, epinephrine-stimulated DNA synthesis activity was inhibited by prazosin but not by propranolol. These results indicate that stimulated DNA synthesis in rat hepatocytes declines with age and that there are two different pathways for epinephrine-stimulated DNA synthesis in the presence or absence of ECF. C1 NATL INST AGING,FRANCIS SCOTT KEY MED CTR,GERONTOL RES CTR,CELLULAR & MOLEC BIOL LAB,BALTIMORE,MD 21224. OI Ishigami, Akihito/0000-0001-7875-7482 NR 37 TC 16 Z9 16 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD FEB PY 1994 VL 158 IS 2 BP 231 EP 236 DI 10.1002/jcp.1041580204 PG 6 WC Cell Biology; Physiology SC Cell Biology; Physiology GA MT404 UT WOS:A1994MT40400003 PM 7906277 ER PT J AU DEBELLIS, MD CHROUSOS, GP DORN, LD BURKE, L HELMERS, K KLING, MA TRICKETT, PK PUTNAM, FW AF DEBELLIS, MD CHROUSOS, GP DORN, LD BURKE, L HELMERS, K KLING, MA TRICKETT, PK PUTNAM, FW TI HYPOTHALAMIC-PITUITARY-ADRENAL AXIS DYSREGULATION IN SEXUALLY ABUSED GIRLS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; MAJOR DEPRESSIVE DISORDER; CORTISOL SECRETION; STIMULATION TEST; NORMAL-CHILDREN; RAT-BRAIN; THERAPEUTIC IMPLICATIONS; PSYCHIATRIC-INPATIENTS; TYROSINE-HYDROXYLASE; SUICIDAL-BEHAVIOR AB Childhood sexual abuse is associated with an increased incidence of age-concurrent and adult psychopathology. Little is known, however, about the biological manifestations and sequelae of childhood sexual abuse. In this study, we characterized the hypothalamic-pituitary-adrenal axis of a self-selected sample of sexually abused and control girls recruited from a prospective longitudinal study. Plasma ACTH and total and free cortisol responses to ovine CRH (oCRH) stimulation were measured in 13 sexually abused and 13 control girls, aged 7-15 yr. Psychiatric profiles and 24-h urinary free cortisol (UFC) measures were also obtained. Sexually abused girls had a greater incidence of suicidal ideation (X(2) = 4.51; df = 1; P < 0.05), suicide attempts (X(2) = 4.51; df = 1; P < 0.05), and dysthymia (X(2) = 8.85; df = 1; P < 0.01) than control girls. Sexually abused girls showed significantly lower basal (t = 2.1; df = 24; P < 0.05), and net oCRH stimulated (t = 2.2; df = 24; P < 0.05) ACTH levels and significantly reduced total ACTH responses (t = 2.5; df = 24; P < 0.05) compared with control subjects. Their total and free basal and oCRH-stimulated plasma cortisol levels and 24-h UFC measures, however, were similar to those in controls. The attenuated plasma ACTH with corresponding robust plasma cortisol responses to oCRH stimulation and normal 24-h UFC measures in sexually abused girls suggest a dysregulatory disorder of the HPA axis in these individuals. This may reflect pituitary hyporesponsiveness to oCRH. The ability of sexually abused subjects to correct for the proposed pituitary hyporesponsiveness to CRH may be related to their young age and the presence of intact glucocorticoid feedback regulatory mechanisms. C1 NIMH, CLIN NEUROENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NIMH, DEV PSYCHOL LAB, BETHESDA, MD 20892 USA. NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NCI, BIOCHEM LAB, BETHESDA, MD 20892 USA. UNIV SO CALIF, DEPT PSYCHOL, LOS ANGELES, CA 90089 USA. RP DEBELLIS, MD (reprint author), UNIV PITTSBURGH, WESTERN PSYCHIAT INST & CLIN, DEPT CHILD & ADOLESCENT PSYCHIAT, PITTSBURGH, PA 15213 USA. RI Kling, Mitchel/F-4152-2010; Burke, Lillian/A-7334-2008 OI Kling, Mitchel/0000-0002-2232-1409; NR 52 TC 334 Z9 335 U1 2 U2 14 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB PY 1994 VL 78 IS 2 BP 249 EP 255 DI 10.1210/jc.78.2.249 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MW717 UT WOS:A1994MW71700003 PM 8106608 ER PT J AU DICHEK, HL NIEMAN, LK OLDFIELD, EH PASS, HI MALLEY, JD CUTLER, GB AF DICHEK, HL NIEMAN, LK OLDFIELD, EH PASS, HI MALLEY, JD CUTLER, GB TI A COMPARISON OF THE STANDARD HIGH-DOSE DEXAMETHASONE SUPPRESSION TEST AND THE OVERNIGHT 8-MG DEXAMETHASONE SUPPRESSION TEST FOR THE DIFFERENTIAL-DIAGNOSIS OF ADRENOCORTICOTROPIN-DEPENDENT CUSHINGS-SYNDROME SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; BRONCHIAL CARCINOID-TUMORS; ECTOPIC ACTH SYNDROME; STIMULATION TEST; CORTISOL AB To improve the overnight 8-mg dexamethasone (DEX) suppression test (DST) for differential diagnosis of Cushing's syndrome and to develop optimal criteria for its interpretation, we increased the number of blood samples and measured the suppression of both plasma ACTH and cortisol. Forty-one patients who were subsequently proven at surgery to have Cushing's syndrome were studied (34 Cushing's disease and 7 ectopic ACTH secretion). DEX (8 mg, orally) was administered at 2300 h. Blood samples for ACTH and cortisol measurements were obtained at 0800, 0830, and 0900 h on the day before and at 0700, 0800, 0900, and 1000 h on the morning after DEX treatment. The conventional 6-day DST was also performed, with measurement of both urinary free cortisol and urinary 17-hydroxysteroids as indices of suppression. Optimal criteria for the diagnosis of Cushing's disease were developed for both the overnight 8-mg and the 6-day tests using receiver operating characteristic curves. The results were compared with those using the previously published criteria for diagnosis of Cushing's disease by the overnight 8-mg test (>50% suppression of plasma cortisol at 0700-0800 h). In our patients, the previously published criterion for the overnight 8-mg test yielded high sensitivity (88%), but low specificity (57%), in making the diagnosis of Cushing's disease. When the time of cortisol measurement and the diagnostic criteria for Cushing's disease were revised to achieve 100% specificity, the sensitivity of the overnight 8-mg test was 71%, which was not significantly different from that of the 6-day test (79%; P = NS). Addition of plasma ACTH levels to the test did not improve diagnostic accuracy compared to that with measurement of plasma cortisol levels alone. When the revised 8-mg overnight dexamethasone suppression test was combined with the 6-day dexamethasone suppression test, sensitivity increased to 91%, with a specificity of 100%, which was significantly better than that of the overnight 8-mg test alone (P < 0.002). We conclude that the overnight 8-mg DST has low specificity for the diagnosis of Cushing's disease when performed as originally described. However, with revised sampling times and diagnostic criteria, the overnight test has sensitivity and specificity similar to those of the conventional 6-day DST. The diagnostic performance of a criterion that combines the results of both tests is better than the diagnostic performance of either test alone. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NINCDS, SURG NEUROL BRANCH, BETHESDA, MD 20892 USA. NCI, SURG BRANCH, BETHESDA, MD 20892 USA. RP DICHEK, HL (reprint author), NIH, DIV COMP RES & TECHNOL, PERSONAL COMP BRANCH, 9000 ROCKVILLE PIKE, BLDG 10, BETHESDA, MD 20892 USA. NR 25 TC 83 Z9 89 U1 1 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 FEB PY 1994 VL 78 IS 2 BP 418 EP 422 DI 10.1210/jc.78.2.418 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MW717 UT WOS:A1994MW71700032 PM 8106630 ER PT J AU SCHUTZ, CG VLAHOV, D ANTHONY, JC GRAHAM, NMH AF SCHUTZ, CG VLAHOV, D ANTHONY, JC GRAHAM, NMH TI COMPARISON OF SELF-REPORTED INJECTION FREQUENCIES FOR PAST 30 DAYS AND 6 MONTHS AMONG INTRAVENOUS-DRUG-USERS SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE SUBSTANCE ABUSE; METHODOLOGY; HUMAN IMMUNODEFICIENCY VIRUS; INJECTION FREQUENCY ID BEHAVIORS AB In this study we compared two parallel self-reported measures that now are being used to assess the recent frequency of intravenous drug use. The study sample consisted of 926 HIV seronegative drug users recruited for participation in HIV research. During a standard interview with each drug user, we first asked about injections in the past 30 days, and then about injections in the past 6 months. The correlation between reports on the past 6 months and the past 30 days was appreciable when all injections were considered (Spearman correlation coefficient rho = 0.78). It increased when the sample was restricted to subjects who reported injections in the past month (rho = 0.88). This restriction resulted in a 15% reduction of the sample size, since 137 participants reported drug use in the previous 6 months but not in the previous 30 days. Concordance tended to be slightly higher for reported frequencies of heroin injections than for cocaine injections, and for men as compared to women. The observed levels of concordance indicate that in many instances both approaches can yield comparable results. Nevertheless the choice of 30 days recall vs 6 months recall must rest upon the specific research questions of each investigation. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MENTAL HYG,BALTIMORE,MD 21205. NIDA,ADDICT RES CTR,ETIOL BRANCH,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. FU NIDA NIH HHS [DA 05911, DA04334] NR 10 TC 36 Z9 36 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD FEB PY 1994 VL 47 IS 2 BP 191 EP 195 DI 10.1016/0895-4356(94)90024-8 PG 5 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA MY336 UT WOS:A1994MY33600009 PM 8113828 ER PT J AU ERPS, LT RITTER, JK HERSH, JH BLOSSOM, D MARTIN, NC OWENS, IS AF ERPS, LT RITTER, JK HERSH, JH BLOSSOM, D MARTIN, NC OWENS, IS TI IDENTIFICATION OF 2 SINGLE-BASE SUBSTITUTIONS IN THE UGT1 GENE LOCUS WHICH ABOLISH BILIRUBIN URIDINE-DIPHOSPHATE GLUCURONOSYLTRANSFERASE ACTIVITY IN-VITRO SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Reprint DE CRIGLER-NAJJAR TYPE I; HYPERBILIRUBINEMIA; RESTRICTION FRAGMENT LENGTH POLYMORPHISM; POINT MUTATION; DNA SEQUENCE ANALYSIS ID CRIGLER-NAJJAR SYNDROME; UDP-GLUCURONOSYLTRANSFERASE; LIVER; COMPLEX; PHENOL; EXPRESSION; CLONING; PATIENT AB Accumulating evidence indicates that mutations in the human UGT1 gene locus abolish hepatic bilirubin UDP-glucuronosyltransferase activity and cause the subsequent accumulation of bilirubin to toxic levels in patients with Crigler-Najjar type 1 (CN-I). Genetic and biochemical criteria are required to link CN-I with mutations in UGT1. Here we present analysis of mutations at the UGT1 locus in three individuals that were clinically diagnosed with CN-I (two related and one unrelated). Each patient carries a single base substitution that alters conserved residues in the transferase enzyme molecule, serine to phenylalanine at codon 376 and glycine to glutamic acid at codon 309. Each was homozygous for the defect as demonstrated by sequencing and RFLPs. Mutant cDNAs, constructed by site-directed mutagenesis, inserted into expression vectors, and transfected into COS-1 cells, supported the synthesis of the bilirubin transferase protein but only cells transfected with the wild-type cDNA expressed bilirubin UDP-glucuronosyltransferase activity. The data provide conclusive evidence that alterations at Gly 309 and Ser 376 are the genetic basis for CN-I in these families. These results suggest that the two codons, located in conserved regions of the molecule, are part of the active site of the bilirubin enzyme. C1 UNIV LOUISVILLE,SCH MED,DEPT PEDIAT,LOUISVILLE,KY 40292. NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. LOS ALMOS MED CTR,CHILDRENS CLIN,LOS ALAMOS,NM 87544. RP ERPS, LT (reprint author), UNIV LOUISVILLE,SCH MED,DEPT BIOCHEM,LOUISVILLE,KY 40292, USA. NR 22 TC 43 Z9 46 U1 1 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 1994 VL 93 IS 2 BP 564 EP 570 DI 10.1172/JCI117008 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA MY296 UT WOS:A1994MY29600019 PM 7906695 ER PT J AU WU, T LEVINE, SJ LAWRENCE, MG LOGUN, C ANGUS, CW SHELHAMER, JH AF WU, T LEVINE, SJ LAWRENCE, MG LOGUN, C ANGUS, CW SHELHAMER, JH TI INTERFERON-GAMMA INDUCES THE SYNTHESIS AND ACTIVATION OF CYTOSOLIC PHOSPHOLIPASE A(2) SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE INTERFERON-GAMMA; CYTOSOLIC PHOSPHOLIPASE A(2); ARACHIDONIC ACID; EPITHELIAL CELLS ID ARACHIDONIC-ACID; GROWTH-FACTOR; TRANSCRIPTIONAL REGULATION; EPITHELIAL-CELLS; C-FOS; EXPRESSION; 15-LIPOXYGENASE; RELEASE; MUCOSA; ASTHMA AB Both IFN-alpha/beta and IFN-gamma have recently been demonstrated to induce a rapid but transient activation of phospholipase A(2) (PLA(2)) in BALB/c 3T3 fibroblasts and a human neuroblastoma cell line. We report that IFN-gamma induces the synthesis and prolonged activation of cytosolic phospholipase A(2) (cPLA(2)) in a human bronchial epithelial cell line (BEAS 2B). Treatment of the cells with IFN-gamma (300 U/ml) increased the release of [H-3]arachidonic acid (AA) from prelabeled cells with a maximal effect at 12 h after stimulation. The increased [H-3]AA release was inhibited by the PLA(2) inhibitor p-bromophenacyl bromide (10(-5) M). Calcium ionophore A23187 (10(-5) M) further increased the [H-3]AA release from the IFN-gamma-treated cells. Subcellular enzyme activity assay revealed that IFN-gamma increased PLA(2) activity in both the cytosol and membrane fractions with a translocation of the cPLA(2) to cell membranes in a Ca2(+)-free cell lysing buffer. Treatment with IFN-gamma also induced the release of 15-HETE, an arachidonic acid metabolite. Immunoblot showed that IFN-gamma induced the synthesis of cPLA(2) protein. Nuclear run-on assay demonstrated that IFN-gamma initiated cPLA(2) gene transcription within 15 min, and this effect was sustained at 4 h and returned to near control level at 12 h. The cPLA(2) mRNA level was assayed by reverse transcription and PCR. IFN-gamma was found to increase the cPLA(2) mRNA after 2-24 h treatment. Furthermore, the IFN-gamma induced cPLA(2) mRNA increase was blocked by inhibitors of protein kinase C and calcium/calmodulin-dependent protein kinases, suggesting the involvement of these protein kinases in IFN-gamma-induced gene expression of cPLA(2). This study shows that IFN-gamma induces the synthesis and prolonged activation of cPLA(2). C1 NIH,DEPT CRIT CARE MED,BETHESDA,MD 20892. NR 40 TC 78 Z9 79 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 1994 VL 93 IS 2 BP 571 EP 577 DI 10.1172/JCI117009 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA MY296 UT WOS:A1994MY29600020 PM 8113394 ER PT J AU CLERICI, M WYNN, TA BERZOFSKY, JA BLATT, SP HENDRIX, CW SHER, A COFFMAN, RL SHEARER, GM AF CLERICI, M WYNN, TA BERZOFSKY, JA BLATT, SP HENDRIX, CW SHER, A COFFMAN, RL SHEARER, GM TI ROLE OF INTERLEUKIN-10 IN T-HELPER CELL DYSFUNCTION IN ASYMPTOMATIC INDIVIDUALS INFECTED WITH THE HUMAN-IMMUNODEFICIENCY-VIRUS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE CYTOKINES; INTERLEUKIN-2; INTERLEUKIN-10; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; T LYMPHOCYTES ID CYTOKINE PRODUCTION; HOMOSEXUAL MEN; TH2 CLONES; HIV; IL-10; PROLIFERATION; ANTIBODY; RECOGNITION; MONOCYTES; RESPONSES AB The loss of T helper cell (TH) function in asymptomatic HIV type 1-infected individuals occurs before the decline in CD4(+) T cells. At least part of the loss in TH function results from changes in immunoregulatory cytokine profiles. To investigate the role of IL-10 in such dysregulation, we tested whether: (a) expression of IL-10-specific mRNA would be upregulated in PBMC from asymptomatic, HIV-infected (HIV+) individuals; (b) PBMC from these same individuals would produce increased levels of IL-10 when stimulated in vitro with phytohemagglutinin; and (c) defective antigen-specific TH function could be restored by anti-IL-10 antibody. We observed that IL-10-specific mRNA was marginally upregulated, and increased levels of IL-10 were produced by PBMC from HIV+ individuals compared with PBMC from uninfected individuals, Those individuals whose TH function was more severely compromised produced higher levels of IL-10. Additionally, defective antigen-specific TH function in vitro could be reversed by anti-IL-10 antibody, including the response to HIV envelope synthetic peptides. Furthermore, the antigen-specific TH responses of HIV-uninfected PBMC could be reduced with IL-10, a process reversed by anti-IL-10. These results confirm that the early loss of TH function in HIV+ individuals is due at least in part to cytokine-induced immune dysregulation, and support the hypothesis of a switch from a predominant type 1 state to a predominant type 2 condition in HIV infection. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NCI,METAB BRANCH,BETHESDA,MD 20892. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. DNAX RES INST MOLEC & CELLULAR BIOL INC,PALO ALTO,CA 94304. WILFORD HALL USAF MED CTR,HIV UNIT,SAN ANTONIO,TX 78236. RI Wynn, Thomas/C-2797-2011; Hendrix, Craig/G-4182-2014 OI Hendrix, Craig/0000-0002-5696-8665 NR 51 TC 355 Z9 355 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 1994 VL 93 IS 2 BP 768 EP 775 DI 10.1172/JCI117031 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA MY296 UT WOS:A1994MY29600042 PM 8113410 ER PT J AU ROSEN, BI PARWANI, AV LOPEZ, S FLORES, J SAIF, LJ AF ROSEN, BI PARWANI, AV LOPEZ, S FLORES, J SAIF, LJ TI SEROTYPIC DIFFERENTIATION OF ROTAVIRUSES IN-FIELD SAMPLES FROM DIARRHEIC PIGS BY USING NUCLEIC-ACID PROBES SPECIFIC FOR PORCINE VP4 AND HUMAN AND PORCINE VP7 GENES SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID ANTIGENIC CHARACTERIZATION; HYBRIDIZATION; SEQUENCE; YM; VACCINE; ORIGIN; BOVINE; RNA AB Of 216 fecal and intestinal samples collected from nursing or weaned diarrheic pigs in the United States and Canada, 57 were identified as group A rotavirus positive by RNA electrophoresis and silver staining. Fifty-seven and 52 rotavirus-positive samples were analyzed by hybridization with Gottfried and OSU PCR-derived gene 9 and 4 probes, respectively. Only 17 samples were identified with either homologous VP4 (P) or VP7 (G)-coding genes or both. One rotavirus identified as G4 and P7 was similar to the previously characterized interserotype rotavirus, SB-1A. Additional hybridization analyses were performed with PCR-derived probes prepared from gene 9 cDNA of the human rotaviruses Wa (G1), DS-1 (G2), and P (G3) and of the porcine rotavirus YM (G11). Eleven of 52 samples collected and analyzed from swine in Ohio, California, and Nebraska were identified as G11. No samples with G1-, G2-, or G3-type specificities were detected among the 25 of 57 rotavirus-positive samples analyzed with human rotavirus-derived probes. Further investigations with a PCR-derived gene 4 probe prepared from porcine rotavirus YM revealed hybridization specificities similar to those of the OSU gene 4 probe. C1 OHIO STATE UNIV,OHIO AGR RES & DEV CTR,FOOD ANIM HLTH RES PROGRAM,WOOSTER,OH 44691. UNIV NACL AUTONOMA MEXICO,CTR INVEST INGN GENET & BIOTECNOL,DEPT BIOL MOLEC,CUERNAVACA 62271,MORELOS,MEXICO. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. NR 28 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD FEB PY 1994 VL 32 IS 2 BP 311 EP 317 PG 7 WC Microbiology SC Microbiology GA MR792 UT WOS:A1994MR79200006 PM 8150940 ER PT J AU ARBUCK, SG AF ARBUCK, SG TI PACLITAXEL - WHAT SCHEDULE - WHAT DOSE SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material RP ARBUCK, SG (reprint author), NCI,BETHESDA,MD 20892, USA. NR 16 TC 34 Z9 34 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 1994 VL 12 IS 2 BP 233 EP 236 PG 4 WC Oncology SC Oncology GA MW706 UT WOS:A1994MW70600001 PM 7509379 ER PT J AU FOSS, FM KOC, Y STETLERSTEVENSON, MA NGUYEN, DT OBRIEN, MC TURNER, R SAUSVILLE, EA AF FOSS, FM KOC, Y STETLERSTEVENSON, MA NGUYEN, DT OBRIEN, MC TURNER, R SAUSVILLE, EA TI COSTIMULATION OF CUTANEOUS T-CELL LYMPHOMA-CELLS BY INTERLEUKIN-7 AND INTERLEUKIN-2 - POTENTIAL AUTOCRINE OR PARACRINE EFFECTORS IN THE SEZARY-SYNDROME SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MYCOSIS-FUNGOIDES; GROWTH-FACTOR; RECOMBINANT INTERLEUKIN-7; FETAL THYMOCYTES; PERIPHERAL-BLOOD; TYROSINE KINASE; PROLIFERATION; RECEPTOR; DIFFERENTIATION C1 NCI,NAVY MED ONCOL BRANCH,PATHOL LAB,BETHESDA,MD. NCI,BIOL CHEM LAB,BETHESDA,MD 20892. RP FOSS, FM (reprint author), BOSTON UNIV,MED CTR,MED ONCOL SECT,88 E NEWTON ST,BOSTON,MA 02118, USA. RI KOC, YENER/L-9529-2015 OI KOC, YENER/0000-0002-3919-9649 NR 45 TC 43 Z9 43 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 1994 VL 12 IS 2 BP 326 EP 335 PG 10 WC Oncology SC Oncology GA MW706 UT WOS:A1994MW70600015 PM 8113839 ER PT J AU FEUER, EJ FREY, CM BRAWLEY, OW NAYFIELD, SG CUNNINGHAM, JB GELLER, NL BOSL, GJ KRAMER, BS AF FEUER, EJ FREY, CM BRAWLEY, OW NAYFIELD, SG CUNNINGHAM, JB GELLER, NL BOSL, GJ KRAMER, BS TI AFTER A TREATMENT BREAKTHROUGH - A COMPARISON OF TRIAL AND POPULATION-BASED DATA FOR ADVANCED TESTICULAR CANCER SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GERM-CELL TUMORS; COMBINATION CHEMOTHERAPY; POOR-RISK; PROGNOSTIC FACTORS; STAGE MIGRATION; ETOPOSIDE; BLEOMYCIN; SURVIVAL; VINBLASTINE; EXPERIENCE C1 NCI,DIV CANC PREVENT & CONTROL,EARLY DETECT & COMMUNITY ONCOL PROGRAM,BETHESDA,MD. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BIOSTAT RES BRANCH,BETHESDA,MD. GEISINGER MED CTR,DANVILLE,PA. MEM SLOAN KETTERING CANC CTR,DEPT MED,DIV SOLID TUMOR ONCOL,GENITOURINARY ONCOL SERV,NEW YORK,NY. RP FEUER, EJ (reprint author), NCI,DIV CANC PREVENT & CONTROL,SURVEILLANCE PROGRAM,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 27 TC 46 Z9 46 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 1994 VL 12 IS 2 BP 368 EP 377 PG 10 WC Oncology SC Oncology GA MW706 UT WOS:A1994MW70600021 PM 7509384 ER PT J AU DENICOFF, KD MEGLATHERY, SB POST, RM TANDECIARZ, SI AF DENICOFF, KD MEGLATHERY, SB POST, RM TANDECIARZ, SI TI EFFICACY OF CARBAMAZEPINE COMPARED WITH OTHER AGENTS - A CLINICAL-PRACTICE SURVEY SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID ALCOHOL WITHDRAWAL SYMPTOMS; LITHIUM-CARBONATE; ACUTE MANIA; MIXED MANIA; BENZODIAZEPINE WITHDRAWAL; CALCIUM-ANTAGONISTS; AFFECTIVE-ILLNESS; BIPOLAR DISORDER; FOLLOW-UP; CLONAZEPAM AB Background: To gain an impression of the experience with and efficacy of carbamazepine relative to other agents and relative to its use in treating psychiatric and neurologic disorders in general clinical practice, a survey was distributed in 1988 to psychiatrists practicing in the United States. Method: The survey was mailed to 9030 members of the American Psychiatric Association (APA) who had expressed an interest in the study and treatment of affective disorders in a 1982 APA survey. The survey sampled clinicians' experience of the efficacy and side effects of carbamazepine in a number of psychiatric and neurologic conditions. Each clinician also provided global impression ratings of the efficacy of a variety of traditional and novel treatments. Results: Completed surveys were returned by 2543 (28%) physicians. Carbamazepine was reported to be moderately to markedly effective in the following percentage of patients: partial complex seizures, 85.2%; generalized seizures, 82.9%; trigeminal neuralgia, 81.5%; mania prophylaxis, 72.9%; acute bipolar depression, 67.5%; intermittent explosive disorder, 65.2%; acute mania, 62.2%; schizoaffective disorder, 58.8%; other pain syndromes, 51.2%; posttraumatic stress disorder, 48.1%; borderline personality disorder, 43.0%; unipolar depression, 32.2%; schizophrenia, 25.7%; and alcohol withdrawal, 15.9%. About 4.4% of the patients reported were withdrawn from carbamazepine because of side effects. Conclusion: Carbamazepine was widely used to treat a variety of psychiatric conditions in 1988 and found to be of use in the acute and long-term treatment of bipolar illness. It was rated slightly less effective than lithium, electroconvulsive therapy, or neuroleptics, but more effective than several other agents. The results of the survey highlight many areas in need of further systematic investigation. RP DENICOFF, KD (reprint author), NATL INST MENTAL HLTH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892, USA. NR 57 TC 28 Z9 28 U1 1 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD FEB PY 1994 VL 55 IS 2 BP 70 EP 76 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA NB402 UT WOS:A1994NB40200005 PM 8077157 ER PT J AU MARKOVIC, M FOWLER, BO BROWN, WE AF MARKOVIC, M FOWLER, BO BROWN, WE TI OCTACALCIUM PHOSPHATE CARBOXYLATES .4. KINETICS OF FORMATION AND SOLUBILITY OF OCTACALCIUM PHOSPHATE SUCCINATE SO JOURNAL OF CRYSTAL GROWTH LA English DT Article ID CRYSTALS; APATITE; SYSTEM AB Kinetic and thermodynamic studies of octacalcium phosphate succinate (OCP-SUCC), Ca8(HPO4)2-x(succ)x(PO4)4.yH2O, where 0.8 < x < 1.0 and 5.5 < y < 6.5, broaden the present knowledge in the chemistry of octacalcium phosphate carboxylates. The kinetics of formation of OCP-SUCC by conversion of alpha-tricalcium phosphate (alpha-TCP), alpha-Ca3(PO4)2, in ammonium succinate solutions was followed at varied initial pH, I approximately 0.5 mol dm-3, 37-degrees-C. The changes in the liquid phase were monitored by pH measurements. Solid phases were characterized by means of chemical analyses, X-ray diffraction and infrared spectroscopy. The rate of conversion decreased with increasing initial pH. In the solubility experiments the concentrations of calcium, phosphate, succinate, ammonium and pH were determined in solutions equilibrated with OCP-SUCC (6.1 < pH < 7.4). Utilizing these data and association constants of phosphoric and succinic acid and stability constants of the soluble complexes, the solubility product of OCP-SUCC, K(s) = c8(Ca2+)c1.07(H+)c0.93(succ2-)C5.07(PO43-), was determined: pK(s)(OCP-SUCC) = 68.4 +/- 0.9 at I = 0.5 mol dm-3, 37-degrees-C. C1 NIDR,NATL INST STAND & TECHNOL,BONE RES BRANCH,RES PROGRAM,BETHESDA,MD 20892. RP MARKOVIC, M (reprint author), NATL INST STAND & TECHNOL,PAFFENBARGER RES CTR,AMER DENT ASSOC HLTH FDN,GAITHERSBURG,MD 20899, USA. NR 27 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-0248 J9 J CRYST GROWTH JI J. Cryst. Growth PD FEB PY 1994 VL 135 IS 3-4 BP 533 EP 538 DI 10.1016/0022-0248(94)90144-9 PG 6 WC Crystallography; Materials Science, Multidisciplinary; Physics, Applied SC Crystallography; Materials Science; Physics GA MZ054 UT WOS:A1994MZ05400019 ER PT J AU QUEZADO, ZMN HOFFMAN, WD WINKELSTEIN, JA YATSIV, I KOEV, CA CORK, LC ELIN, RJ EICHACKER, PQ NATANSON, C AF QUEZADO, ZMN HOFFMAN, WD WINKELSTEIN, JA YATSIV, I KOEV, CA CORK, LC ELIN, RJ EICHACKER, PQ NATANSON, C TI THE 3RD COMPONENT OF COMPLEMENT PROTECTS AGAINST ESCHERICHIA-COLI ENDOTOXIN-INDUCED SHOCK AND MULTIPLE ORGAN FAILURE SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID GENETICALLY-DETERMINED DEFICIENCY; GRAM-NEGATIVE BACTEREMIA; HUMAN SEPTIC SHOCK; CARDIOVASCULAR DYSFUNCTION; ANAPHYLATOXINS C3A; 3RD COMPONENT; CANINE MODEL; LUNG INJURY; INVITRO; ACTIVATION AB We investigated whether the third component of complement (C3) is involved in the pathophysiology of endotoxic shock, and if it is involved, whether it plays a protective role or whether it mediates shock and multiple organ failure. In a prospective, controlled investigation, six Brittany spaniels that were homozygous for a genetically determined deficiency of C3 (C3 deficient, < 0.003% of normal serum C3 levels) and six heterozygous littermates (controls, approximate to 50% of mean normal serum C3 level) were given 2 mg/kg of reconstituted Escherichia coli 026:B6 acetone powder as a source of endotoxin, intravenously. All animals were given similar fluid and prophylactic antibiotic therapy, and had serial hemodynamic variables obtained. After E. coli endotoxin infusion, CS-deficient animals had higher peak levels of endotoxin and less of a rise in temperature than controls (P < 0.05). During the first 4 h after E. coli endotoxin infusion, C3-deficient animals had significantly greater decreases in mean central venous pressure and mean pulmonary artery pressure than controls (P < 0.02). During the first 48 h after E. coli endotoxin infusion, C3-deficient animals had significantly greater decreases in mean arterial pH, left ventricular ejection fraction, and mean pulmonary capillary wedge pressure, and greater increases in mean arterial lactate, arterial-alveolar O-2 gradient, and transaminases (aspartate aminotransferase and alanine aminotransferase) than controls, (all P < 0.05). After E. coli endotoxin infusion, C3-deficient animals compared to controls had significantly less of a decrease in mean C5 levels (P < 0.01), but similar (P = NS) increases in circulating tumor necrosis factor levels, bronchoalveolar lavage neutrophils, and protein, and similar (P = NS) decreases in blood leukocytes and platelets. Two of six C3-deficient animals and two of six controls died. In summary, after intravenous infusion of E. coli endotoxin, canines with C3 deficiency have decreased endotoxin clearance and worse E. coli endotoxin-induced shock and organ damage. Thus, the third component of the complement system plays a beneficial role in the host defense against E. coli endotoxic shock. C1 NIH,DEPT CLIN PATHOL,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH MED,DIV COMPARAT MED,BALTIMORE,MD 21287. CHILDRENS NATL MED CTR,DEPT CRIT CARE,WASHINGTON,DC 20010. RP QUEZADO, ZMN (reprint author), NIH,DEPT CRIT CARE MED,BLDG 10,ROOM 7D43,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 NR 46 TC 47 Z9 47 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 1 PY 1994 VL 179 IS 2 BP 569 EP 578 DI 10.1084/jem.179.2.569 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA MU129 UT WOS:A1994MU12900021 PM 8294868 ER PT J AU PUNT, JA OSBORNE, BA TAKAHAMA, Y SHARROW, SO SINGER, A AF PUNT, JA OSBORNE, BA TAKAHAMA, Y SHARROW, SO SINGER, A TI NEGATIVE SELECTION OF CD4(+)CD8(+) THYMOCYTES BY T-CELL RECEPTOR-INDUCED APOPTOSIS REQUIRES A COSTIMULATORY SIGNAL THAT CAN BE PROVIDED BY CD28 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID IMMATURE CD4+8+ THYMOCYTES; CLONAL DELETION; MONOCLONAL-ANTIBODY; SURFACE-ANTIGEN; DENDRITIC CELLS; FLOW-CYTOMETRY; EXPRESSION; THYMUS; TOLERANCE; DEATH AB CD4(+)CD8(+) thymocytes expressing self-reactive T cell antigen receptors (TCR) are deleted in the thymus as a consequence of TCR/self-antigen/major histocompatibility complex interactions. However, the signals that are necessary to initiate clonal deletion have not yet been clarified. Here we demonstrate that TCR engagement does not efficiently induce apoptosis of CD4(+)CD8(+) thymocytes, although it generates signals that increase expression of CD5, a thymocyte differentiation marker. In fact, TCR signals fail to induce thymocyte apoptosis even when augmented by simultaneous engagement with CD4 or lymphocyte function 1-associated molecules. In marked contrast, signals generated by engagement of both TCR and the costimulatory molecule CD28 potently induce apoptosis of CD4(+)CD8(+) thymocytes. Thus, the present results define a requirement for both TCR and costimulatory signals for thymocyte apoptosis and identify CD28 as one molecule that is capable of providing the necessary costimulus. These results provide a molecular basis for differences among cell types in their ability to mediate negative selection of developing thymocytes. C1 UNIV MASSACHUSETTS,DEPT VET & ANIM SCI,PAIGE LAB,AMHERST,MA 01003. RP PUNT, JA (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B-17,BETHESDA,MD 20892, USA. FU NIGMS NIH HHS [GM-47922] NR 37 TC 218 Z9 219 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 1 PY 1994 VL 179 IS 2 BP 709 EP 713 DI 10.1084/jem.179.2.709 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA MU129 UT WOS:A1994MU12900035 PM 8294878 ER PT J AU MAURER, D FIEBIGER, E REININGER, B WOLFFWINISKI, B JOUVIN, MH KILGUS, O KINET, JP STINGL, G AF MAURER, D FIEBIGER, E REININGER, B WOLFFWINISKI, B JOUVIN, MH KILGUS, O KINET, JP STINGL, G TI EXPRESSION OF FUNCTIONAL HIGH-AFFINITY IMMUNOGLOBULIN-E RECEPTORS (FC-EPSILON-RI) ON MONOCYTES OF ATOPIC INDIVIDUALS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID EPIDERMAL LANGERHANS CELLS; ALVEOLAR MACROPHAGES; IGE; RELEASE; PROTEIN; SUBUNIT; FAMILY; GENE AB Suggestive evidence indicates that immunoglobulin E (IgE)-dependent activation of mononuclear phagocytes plays an important pathogenic role in allergic tissue inflammation. Prevailing opinion holds that low affinity IgE receptors are the relevant IgE-binding structures on monocytes/ macrophages and that functional events occurring after cross-linking of membrane-bound IgE on these cells are mediated by these receptors. Here we demonstrate that peripheral blood monocytes can bind monomeric IgE via the high affinity IgE receptor (Fc epsilon RI) and that Fc epsilon RI expression on these cells is upregulated in atopic persons. Further, we demonstrate that, upon monocyte adherence to substrate, bridging of monocyte Fc epsilon RI is followed by cell activation. We propose that direct interaction of multivalent allergen with Fc epsilon RI(+)-bound IgE on mononuclear phagocytes results in cell signaling via Fc epsilon RI and that the biological consequences of this event may critically influence the outcome of allergic reactions. C1 VIENNA INT RES COOPERAT CTR,A-1235 VIENNA,AUSTRIA. SANDOZ GMBH,RES INST,A-1235 VIENNA,AUSTRIA. NIAID,MOLEC ALLERGY & IMMUNOL SECT,ROCKVILLE,MD 20892. RP MAURER, D (reprint author), UNIV VIENNA,SCH MED,DEPT DERMATOL,DIV IMMUNOL ALLERGY & INFECT DIS,A-1090 VIENNA,AUSTRIA. NR 24 TC 301 Z9 302 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 1 PY 1994 VL 179 IS 2 BP 745 EP 750 DI 10.1084/jem.179.2.745 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA MU129 UT WOS:A1994MU12900041 PM 8294882 ER PT J AU BURG, MB AF BURG, MB TI MOLECULAR-BASIS FOR OSMOREGULATION OF ORGANIC OSMOLYTES IN RENAL MEDULLARY CELLS SO JOURNAL OF EXPERIMENTAL ZOOLOGY LA English DT Article; Proceedings Paper CT Symposium on Cellular Volume Regulation: Mechanisms and Control CY AUG 09-13, 1992 CL CAMBRIDGE, ENGLAND SP SOC EXPTL BIOL, AMER PHYSIOL SOC, AMER SOC ZOOLOGISTS, CANADIAN SOC ZOOLOGISTS ID PAPILLARY EPITHELIAL-CELLS; KIDNEY ALDOSE REDUCTASE; HIGH EXTRACELLULAR NACL; OSMOTIC REGULATION; XENOPUS-OOCYTES; MDCK CELLS; TRANSPORT; SORBITOL; BETAINE; MYOINOSITOL AB Renal medullary cells are naturally exposed to extremely high and variable interstitial concentrations of NaCl and urea, consequent to operation of the urinary concentrating mechanism. They respond by accumulating large and variable amounts of sorbitol, glycerophosphocholine (GPC), glycine betaine (betaine), myo-inositol (inositol), and taurine both in vivo and in cell cultures. Sorbitol is synthesized from glucose, catalyzed by aldose reductase. Hypertonicity increases aldose reductase activity by raising this enzyme's transcription, mRNA level, and translation, and thereby increases production of sorbitol. GPC is synthesized from choline via phosphatidylcholine. A combination of high NaCl plus urea does not increase GPC synthesis, but does reduce its degradation by inhibiting GPC:choline phosphodiesterase. Betaine, inositol and taurine are taken up into the cells, each by a different sodium-dependent transporter. Hypertonicity increases mRNAs of all three transporters. This is due to increased transcription (at least of the inositol and betaine transporters). The eventual result is greater betaine, inositol and taurine uptake and accumulation. Osmoregulation of net sorbitol and GPC synthesis and of betaine, inositol and taurine transport is slow, requiring hours to days. However, following an acute fall in tonicity, these organic osmolytes exit from the cells within minutes, via specialized efflux mechanisms. As demonstrated by cloning efficiency studies, renal cell survival and growth following hypertonicity depend on the sum of all organic osmolytes that are accumulated; altering one experimentally changes the others to maintain a nearly constant total. Methylamine accumulation protects these cells against high urea; the methylamine that is preferentially accumulated in response to high urea is GPC. (C) 1994 Wiley-Liss, Inc.* RP BURG, MB (reprint author), NIH,BLDG 10,ROOM 6N307,BETHESDA,MD 20892, USA. NR 35 TC 60 Z9 60 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 0022-104X J9 J EXP ZOOL JI J. Exp. Zool. PD FEB 1 PY 1994 VL 268 IS 2 BP 171 EP 175 DI 10.1002/jez.1402680216 PG 5 WC Zoology SC Zoology GA MU645 UT WOS:A1994MU64500015 PM 8301253 ER PT J AU PAK, CC KRUMBIEGEL, M BLUMENTHAL, R AF PAK, CC KRUMBIEGEL, M BLUMENTHAL, R TI INTERMEDIATES IN INFLUENZA-VIRUS PR/8 HEMAGGLUTININ-INDUCED MEMBRANE-FUSION SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID INDUCED CONFORMATIONAL CHANGE; RED-BLOOD-CELLS; LOW PH; HEMAGGLUTININ; FLUORESCENCE; KINETICS; EVENTS AB The fusion kinetics with erythrocyte ghosts of two influenza A virus strains, A/Aichi/2/68 (X:31) and A/PR/8/34 (PR/8), were compared and correlated with the kinetics of haemagglutinin (HA) conformational change. Previously it had been shown that X:31 fuses with liposomes or erythrocytes at 4 degrees C, pH 5 after a lag time of 5 to 10 min whereas PR/8 displayed no fusion with liposomes at that temperature. We have confirmed the absence of cold fusion by PR/8 with erythrocyte ghosts. In contrast to X:31, PR/8 could not be committed to fuse at neutral pH and 37 degrees C by a preincubation at low pH and 4 degrees C. To examine whether the lack of commitment and cold fusion were due to a failure of PR/8 HA to undergo conformational changes at low temperature and pH, we analysed susceptibility of HA to proteinase K digestion, liposome binding to the virus, and immunoprecipitations of HA with conformation-specific antibodies. Although there was little binding of PR/8 to liposomes at 4 degrees C and pH 5, we did observe exposure of the fusion peptide. This study reveals a low temperature intermediate in membrane fusion exhibited by the HA of influenza virus strain PR/8, which involves low pH-induced conformational changes including exposure of the fusion peptide with little interaction of HA with the target membrane. C1 NCI,MEMBRANE STRUCT & FUNCT SECT,BETHESDA,MD 20892. NR 22 TC 26 Z9 26 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD FEB PY 1994 VL 75 BP 395 EP 399 DI 10.1099/0022-1317-75-2-395 PN 2 PG 5 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA MT645 UT WOS:A1994MT64500018 PM 8113761 ER PT J AU SACKS, FM HEBERT, P APPEL, LJ BORHANI, NO APPLEGATE, WB COHEN, JD CUTLER, JA KIRCHNER, KA KULLER, LH ROTH, KJ TAYLOR, JO HENNEKENS, CH AF SACKS, FM HEBERT, P APPEL, LJ BORHANI, NO APPLEGATE, WB COHEN, JD CUTLER, JA KIRCHNER, KA KULLER, LH ROTH, KJ TAYLOR, JO HENNEKENS, CH TI SHORT REPORT - THE EFFECT OF FISH-OIL ON BLOOD-PRESSURE AND HIGH-DENSITY LIPOPROTEIN-CHOLESTEROL LEVELS IN PHASE-I OF THE TRIALS OF HYPERTENSION PREVENTION SO JOURNAL OF HYPERTENSION LA English DT Note DE DIETARY FATS; POLYUNSATURATED FATTY ACIDS; FISH OILS; BLOOD PRESSURE; LIPOPROTEINS; CLINICAL TRIAL; HYPERTENSION ID N-3 FATTY-ACIDS; DIETARY FISH; CARDIOVASCULAR-DISEASE; SERUM-LIPIDS; PLASMA; SUPPLEMENTATION; METABOLISM; MEN AB Objective: To study the effects of moderate doses of fish oil on blood pressure and high-density lipoprotein (HDL)-cholesterol. Methods: The participants were 350 normotensive men and women aged 30-54 years who were enrolled from seven academic medical centers in phase I of the Trials of Hypertension Prevention. They were randomly assigned to receive placebo or 6g purified fish oil once a day, which supplied 3g n-3 polyunsaturated fatty acids for 6 months. Results: Baseline blood pressure was (mean +/- SD) 123 +/- 9/81 +/- 5 mmHg. The mean differences in the blood pressure changes between the fish oil and placebo groups were not statistically significant. There was no tendency for fish oil to reduce blood pressure more in subjects with baseline blood pressure in the upper versus the lower quartile (132/87 versus 114/75 mmHg), low habitual fish consumption (0.4 versus 2.9 times a week) or low baseline plasma levels of n-3 fatty acids. Fish oil increased HDL(2)-cholesterol significantly compared with the placebo group. Subgroup analysis showed this effect to be significant in the women but not in the men. Increases in serum phospholipid n-3 fatty acids were significantly correlated with increases in HDL(2)-cholesterol and decreases in systolic blood pressure. Conclusion: Moderate amounts of fish oil (6g/day) are unlikely to lower blood pressure in normotensive persons, but may increase HDL(2)-cholesterol, particularly in women. C1 HARVARD UNIV,SCH MED,CHANNING LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DIV PREVENT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD. UNIV CALIF DAVIS,DAVIS,CA. UNIV TENNESSEE,MEMPHIS,TN. ST LOUIS UNIV,ST LOUIS,MO 63103. NHLBI,BETHESDA,MD 20892. UNIV MISSISSIPPI,JACKSON,MS 39216. UNIV PITTSBURGH,SCH PUBL HLTH,PITTSBURGH,PA 15260. E BOSTON NEIGHBORHOOD HLTH CTR,BOSTON,MA. RP SACKS, FM (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,665 HUNTINGTON AVE,BOSTON,MA 02115, USA. NR 26 TC 24 Z9 28 U1 0 U2 4 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD FEB PY 1994 VL 12 IS 2 BP 209 EP 213 DI 10.1097/00004872-199402000-00014 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NB143 UT WOS:A1994NB14300014 PM 8021472 ER PT J AU FOWLER, DH KURASAWA, K HUSEBEKK, A COHEN, PA GRESS, RE AF FOWLER, DH KURASAWA, K HUSEBEKK, A COHEN, PA GRESS, RE TI CELLS OF TH2 CYTOKINE PHENOTYPE PREVENT LPS-INDUCED LETHALITY DURING MURINE GRAFT-VERSUS-HOST REACTION - REGULATION OF CYTOKINES AND CD8+ LYMPHOID ENGRAFTMENT SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; LYMPHOCYTES-T; BONE-MARROW; MONOCLONAL-ANTIBODY; CLONES SECRETE; HELPER CELL; DISEASE; ANTIGEN; INTERLEUKIN-4; ACTIVATION AB A murine parent-into-F1 graft-vs-host reaction (GVHR) model that utilizes LPS to induce lethality was used to evaluate the in vivo regulatory role of donor cells of Th2 cytokine phenotype. Transfer of B6 spleen cells into B6C3F1 hosts was lethal when LPS endotoxin (15 mug) was administered on day 7 after cell transfer. Parental cells of Th2 cytokine phenotype were generated by treating B6 mice in vivo with a combination of IL-2 and IL-4 or with high dose IL-2. The CD4-enriched population from these cytokine-treated mice expressed and secreted increased levels of IL-4 and IL-10, with concomitantly decreased IL-2 and IFN-gamma. Cell mixing experiments (parental spleen cells + parental CD4-enriched, Th2-type cells) demonstrated that the Th2-type cells protected F1 hosts from LPS-induced lethality. These mice were analyzed to study possible mechanisms by which this protection was mediated. Compared with mice undergoing LPS-induced lethality during GVHR, Th2-protected mice had: 1) lower levels of donor CD8+ lymphoid engraftment, 2) in vivo suppression of IFN-gamma mRNA, 3) in vivo augmentation of IL-4 mRNA, and 4) a reduction in serum TNF-alpha. We thus conclude that donor cells of Th2 cytokine phenotype prevent LPS-induced, TNF-a-mediated lethality during GVHR, and that this protection is associated with regulation of both cellular- and cytokine-mediated events. As a result, we propose that cells of Th2 cytokine phenotype may represent a novel approach for establishing allogeneic lymphoid engraftment without lethal graft-vs-host disease. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. RP FOWLER, DH (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B51,BETHESDA,MD 20892, USA. NR 38 TC 131 Z9 132 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 1994 VL 152 IS 3 BP 1004 EP 1013 PG 10 WC Immunology SC Immunology GA MV630 UT WOS:A1994MV63000005 PM 7905495 ER PT J AU JARVIS, CD GERMAIN, RN HAGER, GL DAMSCHRODER, M MATIS, LA AF JARVIS, CD GERMAIN, RN HAGER, GL DAMSCHRODER, M MATIS, LA TI TISSUE-SPECIFIC EXPRESSION OF MESSENGER-RNAS ENCODING ENDOGENOUS VIRAL SUPERANTIGENS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAMMARY-TUMOR VIRUS; LONG TERMINAL REPEAT; OPEN READING FRAME; MAJOR HISTOCOMPATIBILITY COMPLEX; MOUSE DENDRITIC CELLS; BONE-MARROW CHIMERAS; REACTIVE T-CELLS; CLONAL DELETION; B-CELLS; HEMATOPOIETIC-CELLS AB The minor lymphocyte stimulating (MLS) superantigens of mice are encoded by open reading frames (ORFs) in the 3' long terminal repeats (LTRs) of endogenous mouse mammary tumor viruses. By stimulating all T cells bearing particular TCR Vbeta proteins, these viral superantigens (v-SAGs) exert profound effects on T cell development and function. We have examined expression of the 1.7 kb mRNA product predicted to encode v-SAG proteins in different cells and tissues of the immune system. The LTR-ORF mRNA was expressed in activated B cells and activated mature CD8 but not CD4 T cells, consistent with previous functional studies assessing MLS activity in these cell types. Little or no message was detected in thymic epithelial cells, macrophages, or dendritic cells, although low levels could be observed in thymic epithelium after southern hybridization to PCR-amplified cDNA. LTR-ORF mRNA was also expressed in immature CD4-CD8- and CD4+CD8+ thymocytes, suggesting selective down-regulation of expression in the T cell lineage after differentiation to the CD4+ phenotype. Thus, among cells of the immune system, v-SAG encoding mRNA is expressed predominantly within the lymphoid lineage. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NCI,DIV CANC ETIOL,MOLEC VIROL LAB,BETHESDA,MD 20892. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. OI Damschroder, Melissa/0000-0001-9453-6532 NR 56 TC 25 Z9 25 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 1994 VL 152 IS 3 BP 1032 EP 1038 PG 7 WC Immunology SC Immunology GA MV630 UT WOS:A1994MV63000008 PM 8301115 ER PT J AU NAKAJIMA, H HENKART, PA AF NAKAJIMA, H HENKART, PA TI CYTOTOXIC LYMPHOCYTE GRANZYMES TRIGGER A TARGET-CELL INTERNAL DISINTEGRATION PATHWAY LEADING TO CYTOLYSIS AND DNA BREAKDOWN SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MEDIATED CYTO-TOXICITY; SERINE PROTEASE; MECHANISMS; SUBSTRATE; LYSIS; PURIFICATION; INHIBITION; PROTECTION; ANTIBODY; GRANULES AB Two approaches have been used to assess the hypothesis that granzymes secreted by cytotoxic lymphocytes act within the target cells to trigger an internal disintegration pathway leading to target cell lysis. The lytic properties of several clones of rat basophilic leukemia cells transfected with either cytolysin (perforin) alone (RBL-cy) or a combination of cytolysin and granzyme A (RBL-cy-gza) were compared with cloned CTL. Analysis of the kinetics of target cell I-125-DNA vs Cr-51 release with three tumor targets showed negligible DNA release with RBL-cy, less extensive I-125-DNA release relative to Cr-51 release with RBL-cy-gza effector cells, whereas CTL caused greater or equal DNA release than Cr-51 release at all time points. Using three different tumor target cells, comparison of RBL-cy-gza and RBL-cy clones in multiple experiments shows that RBL-cy-gza are on average more than threefold more lytic than RBL-cy. This distinction was not seen with red cell targets, in which an internal disintegration pathway does not operate. A second approach to this issue consisted of cytoplasmic loading of tumor target cells with aprotinin, a macromolecular protease inhibitor known to inhibit granzyme A and probably other granzymes. Although the control BSA-loaded target cells were essentially identical to nonloaded targets in all cases, aprotinin-loaded targets showed substantially lower, release of both Cr-51 and I-125-DNA with both CTL and RBL-cy-gza effector cells. In contrast, aprotinin-loaded targets were lysed with the same efficiency as control targets by RBL-cy effector cells. We conclude that secreted granzymes contribute to target lysis by triggering a target cell internal disintegration pathway that leads to both lysis and DNA breakdown. C1 NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B17,BETHESDA,MD 20892. NR 28 TC 86 Z9 90 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 1994 VL 152 IS 3 BP 1057 EP 1063 PG 7 WC Immunology SC Immunology GA MV630 UT WOS:A1994MV63000011 PM 7507956 ER PT J AU YEWDELL, J LAPHAM, C BACIK, I SPIES, T BENNINK, J AF YEWDELL, J LAPHAM, C BACIK, I SPIES, T BENNINK, J TI MHC-ENCODED PROTEASOME SUBUNIT-LMP2 AND SUBUNIT-LMP7 ARE NOT REQUIRED FOR EFFICIENT ANTIGEN PRESENTATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; TOXIC LYMPHOCYTES-T; CLASS-I MOLECULES; PUTATIVE PEPTIDE TRANSPORTER; INFLUENZA HEMAGGLUTININ; SIGNAL SEQUENCE; MUTANT-CELLS; RMA-S; EXPRESSION; PROTEINS AB LMP2 and LMP7 are proteins encoded by MHC genes that are tightly linked to the genes encoding TAP, the transporter that conveys peptides from the cytosol to the endoplasmic reticulum for assembly with MHC class I molecules. LMP2 and LMP7 are subunits of a subset of proteasomes, large molecular assemblies with multi-proteolytic activities believed to degrade damaged and unwanted cellular proteins. Like TAP and class I molecules themselves, expression of LMP genes is enhanced after exposure of cells to IFN-gamma. These findings implicate LMP2 and LMP7 in the cytosolic production of antigenic peptides. Doubts have been cast, however, on the role of LMP2 and LMP7 in Ag processing, because cells lacking these proteins possess class I molecules that contain peptides quantitatively and qualitatively indistinguishable from the peptides bound to class I molecules derived from normal cells. In this paper we show that cells lacking LMP2 and LMP7 present seven TAP-dependent determinants derived from viral proteins. For two determinants, the kinetics of presentation are shown to be similar for LMP-expressing and -nonexpressing cells. We also demonstrate biochemically that peptide is not limiting in the assembly of class I molecules in LMP-nonexpressing cells. These findings provide additional evidence that LMP2 and LMP7 are not required for efficient Ag presentation, and suggest that these proteins have either a more specialized role in the production of class I-associated peptides, or are not involved in the processing of proteins for-association with class I molecules. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP YEWDELL, J (reprint author), NIAID,VIRAL DIS LAB,BETHESDA,MD 20892, USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 FU NIAID NIH HHS [AI 30581] NR 53 TC 81 Z9 82 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 1994 VL 152 IS 3 BP 1163 EP 1170 PG 8 WC Immunology SC Immunology GA MV630 UT WOS:A1994MV63000023 PM 8301122 ER PT J AU ZIEGLER, SF LEVIN, SD JOHNSON, L COPELAND, NG GILBERT, DJ JENKINS, NA BAKER, E SUTHERLAND, GR FELDHAUS, AL RAMSDELL, F AF ZIEGLER, SF LEVIN, SD JOHNSON, L COPELAND, NG GILBERT, DJ JENKINS, NA BAKER, E SUTHERLAND, GR FELDHAUS, AL RAMSDELL, F TI THE MOUSE CD69 GENE - STRUCTURE, EXPRESSION, AND MAPPING TO THE NK GENE-COMPLEX SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL ACTIVATION; CARBOHYDRATE-RECOGNITION DOMAINS; ACUTE LYMPHOBLASTIC-LEUKEMIA; MESSENGER-RNA DEGRADATION; TRANSCRIPTION FACTOR; MULTIGENE FAMILY; CONSTITUTIVE EXPRESSION; PROTEIN-BINDING; ANTIGEN EA-1; KILLER-CELLS AB CD69 is a rapidly induced T cell activation Ag that is also expressed in an inducible fashion on cells of most, if not all, hematopoietic lineages. Molecular cloning has shown that CD69 is a type II-membrane glycoprotein that is a member of the C-type lectin family. In this report we have shown that induction of CD69 mRNA in activated murine thymocytes and T cells is very rapid, peaking between 30 and 60 min poststimulation, and transient, dropping to nearly resting levels by 8 h. An analysis of the mouse CD69 gene structure showed the gene to consist of 5 exons and have a phorbol ester-inducible promoter element within the first 700 bp upstream of the start of transcription. Chromosomal mapping placed the mouse CD69 gene on the long arm of chromosome 6 near the NK gene complex that contains the related NKR-P1 and Ly-49 gene families. The human CD69 gene mapped to chromosome 12p13 near the related NKG2 gene cluster and in a region associated with rearrangements in approximately 10% of cases of childhood acute lymphocytic leukemia. C1 NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,FREDERICK,MD 21702. TARGETED GENET CORP,SEATTLE,WA. NCI,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. ADELAIDE CHILDRENS HOSP INC,DEPT CYTOGENET & MOLEC GENET,ADELAIDE,SA 5006,AUSTRALIA. RP ZIEGLER, SF (reprint author), IMMUNEX RES & DEV CORP,51 UNIV ST,SEATTLE,WA 98101, USA. RI Sutherland, Grant/D-2606-2012 FU NCI NIH HHS [N0I-CO-745101] NR 60 TC 112 Z9 116 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 1994 VL 152 IS 3 BP 1228 EP 1236 PG 9 WC Immunology SC Immunology GA MV630 UT WOS:A1994MV63000031 PM 8301128 ER PT J AU MARCUS, SG PERRYLALLEY, D MULE, JJ ROSENBERG, SA YANG, JC AF MARCUS, SG PERRYLALLEY, D MULE, JJ ROSENBERG, SA YANG, JC TI THE USE OF INTERLEUKIN-6 TO GENERATE TUMOR-INFILTRATING LYMPHOCYTES WITH ENHANCED IN-VIVO ANTITUMOR-ACTIVITY SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE INTERLEUKIN-6; TUMOR-INFILTRATING LYMPHOCYTES; ADOPTIVE IMMUNOTHERAPY; COLLAGEN MATRIX; CYTOKINE ID NECROSIS-FACTOR-ALPHA; STIMULATORY FACTOR-II; MURINE TUMOR; RECOMBINANT INTERLEUKIN-6; ADOPTIVE IMMUNOTHERAPY; GROWTH-FACTOR; CELLS; INVIVO; IMMUNITY; TUMORIGENICITY AB Tumor-infiltrating lymphocytes (TIL) are cytotoxic T cells isolated from solid tumors and expanded in vitro in recombinant interleukin-2 (rIL-2). TIL have antitumor effects in murine models and in some patients with melanoma. In an effort to generate murine TIL with enhanced in vivo therapeutic efficacy, viable tumor cells were coinjected with a collagen matrix plus recombinant human IL-6 (rIL-6) subcutaneously into syngeneic mice to achieve sustained local concentrations of rIL-6 at the tumor site from which TIL were derived. In five separate experiments, single cell suspensions of tumors were admired with either (a) Hanks' balanced salt solution (HBSS), (b) 2% (20 mg/ml) collagen matrix only, (c) 250 mu g rIL-6 only, or (d) 250 mu g rIL-6 in a 2% collagen matrix (prolonged release) before subcutaneous inoculation. These tumors were subsequently resected and TIL were isolated and expanded in vitro. TIL generated from tumors admired with matrix plus rIL-6 were significantly more effective than TIL expanded from tumors admired with HBSS (four of five experiments), TIL from tumors admired with matrix only (five of five experiments), and TIL from tumors admired with rIL-6 only (three of four experiments) in an established tumor treatment model. In no experiment was any other TIL culture superior to TIL grown from tumors augmented with collagen matrix plus rIL-6. These results suggest that strategies designed to increase the local concentrations of cytokines at tumor sites may lead to the generation of more potent TIL for clinical administration. C1 NCI,DIV CANC TREATMENT,SURG BRANCH,BETHESDA,MD 20892. NR 43 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD FEB PY 1994 VL 15 IS 2 BP 105 EP 112 DI 10.1097/00002371-199402000-00003 PG 8 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA MT386 UT WOS:A1994MT38600003 PM 8136942 ER PT J AU MARGOLIN, K ARONSON, FR SZNOL, M ATKINS, MB GUCALP, R FISHER, RI SUNDERLAND, M DOROSHOW, JH ERNEST, ML MIER, JW DUTCHER, JP GAYNOR, ER WEISS, GR AF MARGOLIN, K ARONSON, FR SZNOL, M ATKINS, MB GUCALP, R FISHER, RI SUNDERLAND, M DOROSHOW, JH ERNEST, ML MIER, JW DUTCHER, JP GAYNOR, ER WEISS, GR TI PHASE-II STUDIES OF RECOMBINANT HUMAN INTERLEUKIN-4 IN ADVANCED RENAL-CANCER AND MALIGNANT-MELANOMA SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE INTERLEUKIN-4; RENAL CANCER; MALIGNANT MELANOMA; CYTOKINES; IMMUNOTHERAPY ID TUMOR-NECROSIS-FACTOR; GAMMA-INTERFERON; CELL-GROWTH; LYMPHOCYTES; ALPHA; IL-4; PROLIFERATION; EXPRESSION; MONOCYTES; INVITRO AB Interleukin (IL)-4 is a pluripotent cytokine that stimulates proliferation of activated T-cells and has antineoplastic activity against human renal tumors in animal systems. In phase I trials, IL-4 could be tolerated at doses up to 20 mu g/kg, with dose-limiting toxicities consisting of fever, fluid retention, nasal congestion, and mucositis. We report the results of two separate Phase II trials of IL-4 in 30 patients with metastatic malignant melanoma and 19 patients with advanced renal cancer. IL-4 was administered intravenously every 8 h for 14 doses in two 5-day courses separated by a 9-day interval. The first 27 patients were treated at a dose of 800 mu g/m(2), but after three of these patients developed cardiac toxicities, the dose was decreased to 600 mu g/m(2). One complete response occurred in a patient with metastatic melanoma (duration greater than or equal to 30 months). No responses were seen among the patients with renal cancer. The most frequent side effects were fever, nausea, malaise, nasal congestion, and diarrhea. Reversible hepatic and renal dysfunction were also common. Hypotension was infrequent, but transient weight gain due to fluid retention was common. The major life-threatening toxicities were cardiac and gastrointestinal. Suspected cardiac ischemia was observed in two patients, pericarditis in one, and arrhythmias in two. Three patients had major upper gastrointestinal bleeding without evidence of local tumor. We conclude that IL-4, when given as a single agent on this schedule at maximum tolerated dose, does not possess meaningful activity in renal cancer or melanoma. C1 UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. NCI,CANC THERAPY PROGRAM,BETHESDA,MD. TUFTS UNIV,NEW ENGLAND MED CTR,BOSTON,MA 02111. MONTEFIORE MED CTR,ALBERT EINSTEIN CANC CTR,BRONX,NY 10467. LOYOLA UNIV,STRITCH SCH MED,CHICAGO,IL. UNIV TEXAS,AUDIE MURPHY VET ADM HOSP,HLTH SCI CTR,SAN ANTONIO,TX. RP MARGOLIN, K (reprint author), CITY HOPE NATL MED CTR,DEPT MED ONCOL,1500 E DUARTE RD,DUARTE,CA 91010, USA. NR 22 TC 52 Z9 52 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD FEB PY 1994 VL 15 IS 2 BP 147 EP 153 DI 10.1097/00002371-199402000-00009 PG 7 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA MT386 UT WOS:A1994MT38600009 PM 8136948 ER PT J AU HILDESHEIM, A SCHIFFMAN, MH GRAVITT, PE GLASS, AG GREER, CE ZHANG, T SCOTT, DR RUSH, BB LAWLER, P SHERMAN, ME KURMAN, RJ MANES, MM AF HILDESHEIM, A SCHIFFMAN, MH GRAVITT, PE GLASS, AG GREER, CE ZHANG, T SCOTT, DR RUSH, BB LAWLER, P SHERMAN, ME KURMAN, RJ MANES, MM TI PERSISTENCE OF TYPE-SPECIFIC HUMAN PAPILLOMAVIRUS INFECTION AMONG CYTOLOGICALLY NORMAL WOMEN SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CERVICAL-CANCER; NEOPLASIA; SMOKING; MILD AB Determinants of genital human papillomavirus (HPV) persistence in 393 women initially cytologically normal were investigated by testing them for HPV DNA twice over a median interval of 14.9 months. At each visit, interview information was obtained and a cervicovaginal lavage sample was collected for polymerase chain reaction-based HPV testing. Twenty-six percent of the women were HPV-positive at the first sampling. Data on HPV type was available for 86 HPV-positive women (84%); 35 of these women (41%) had persistent type-specific HPV detection. Persistence decreased with time between samplings. Women aged greater than or equal to 30 years had a higher percentage of persistence (65%) than those less than or equal to 24 years (32%, P=.02). The percentage of persistence was higher among women infected with HPV types known to be cancer-associated (45%) than among those infected with other types (24%,P=.11). These findings were independent of each other and of timing between samplings. Although based on a prevalent cohort, these results are concordant with previous suggestions that HPV infection is usually transient and that cervical cancer may arise from within the subset of women with persistent HPV infection. C1 JOHNS HOPKINS MED INST,DEPT PATHOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH PUBL HLTH,DEPT IMMUNOL & INFECT DIS,BALTIMORE,MD 21218. CETUS CORP,DEPT INFECT DIS,EMERYVILLE,CA 94608. ROCHE MOLEC SYST,DEPT INFECT DIS,ALAMEDA,CA. KAISER PERMANENTE,PORTLAND,OR. RP HILDESHEIM, A (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,ENVIRONM EPIDEMIOL BRANCH,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 26 TC 544 Z9 556 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB PY 1994 VL 169 IS 2 BP 235 EP 240 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA MV829 UT WOS:A1994MV82900001 PM 8106758 ER PT J AU CHOUCHANE, L BOWERS, FS SAWASDIKOSOL, S SIMPSON, RM KINDT, TJ AF CHOUCHANE, L BOWERS, FS SAWASDIKOSOL, S SIMPSON, RM KINDT, TJ TI HEAT-SHOCK PROTEINS EXPRESSED ON THE SURFACE OF HUMAN T-CELL LEUKEMIA-VIRUS TYPE I-INFECTED CELL-LINES INDUCE AUTOANTIBODIES IN RABBITS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID STRESS PROTEINS; DISEASE; ACCUMULATION; POLYPEPTIDES; GENES; HSP70 AB Eight human T cell leukemia virus type I (HTLV-I)-infected cell lines were derived in vitro from peripheral blood mononuclear cells of 8 rabbits. Each rabbit was then inoculated with its own HTLV-I-transformed cells, after which all but 1 rabbit had anti-heat-shock protein (hsp) antibodies in sera. Cell line RH/K34, which failed to raise a response to hsp70, caused lethal leukemia when >2 X 10(8) live cells were injected into unrelated outbred rabbits. Rabbits injected with cell-free virus isolated from RH/K34 cells produced anti-hsp70 antibodies and became infected but developed no fatal disease. ELISA inhibition and flow cytometry analyses indicated that hsp molecules are expressed on the surface of RH/K34 and RH/K30, a nonlethal HTLV-I cell line used for comparison; surface hsp expression does not occur normally. Two proteins of similar to 72 and 93 kDa were detected by Western blot in extracts of RH/K30 cells. Presence of anti-hsp70 antibodies correlated with resistance to lethal doses of live RH/K34 cells, suggesting that hsp immunity may influence the outcome of RH/K34 pathogenicity. C1 NIAID,IMMUNOGENET LAB,ROCKVILLE,MD 20852. NR 38 TC 36 Z9 37 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB PY 1994 VL 169 IS 2 BP 253 EP 259 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA MV829 UT WOS:A1994MV82900004 PM 7508967 ER PT J AU TSAI, CC FOLLIS, KE SABO, A GRANT, RF BARTZ, C NOLTE, RE BENVENISTE, RE BISCHOFBERGER, N AF TSAI, CC FOLLIS, KE SABO, A GRANT, RF BARTZ, C NOLTE, RE BENVENISTE, RE BISCHOFBERGER, N TI PREEXPOSURE PROPHYLAXIS WITH 9-(2-PHOSPHONYLMETHOXYETHYL)ADENINE AGAINST SIMIAN IMMUNODEFICIENCY VIRUS-INFECTION IN MACAQUES SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID RHESUS-MONKEYS; ANTIRETROVIRUS ACTIVITY; REPLICATION INVITRO; SIV INFECTION; INVIVO; AIDS; 3'-AZIDO-3'-DEOXYTHYMIDINE; LENTIVIRUSES; VACCINES; THERAPY AB A reverse transcriptase inhibitor, 9-(2-phosphonylmethoxyethyl)adenine (PMEA), was evaluated for efficacy against acute simian immunodeficiency virus (SIV) infection in juvenile macaques (Macaca fascicularis). Macaques were pretreated subcutaneously with PMEA for 48 h before SIV inoculation. Drug treatment continued for an additional 28 days. Efficacy of PMEA was determined by detection of SIV in blood, SIV DNA in peripheral blood mononuclear cells, and SIV antibodies. Protection from acute SIV infection occurred in 83% of macaques treated with 20 mg/kg/day versus 50% of macaques treated with 10 mg/kg/day. Several PMEA-treated macaques developed mild dermatitis that disappeared when the 4-week therapy ended. The results of these experiments indicate that preexposure prophylaxis with PMEA can prevent acute SIV infection in macaques. Since PMEA demonstrates profound inhibition of retrovirus infection, it may have utility as a chemoprophylactic agent for humans exposed to SIV or human immunodeficiency virus. C1 UNIV WASHINGTON, REG PRIMATE RES CTR, SEATTLE, WA 98195 USA. NCI, VIRAL CARCINOGENESIS LAB, FREDERICK, MD USA. GILEAD SCI, FOSTER CITY, CA USA. FU NCRR NIH HHS [RR-00166]; NIAID NIH HHS [AI-15120] NR 29 TC 46 Z9 46 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB PY 1994 VL 169 IS 2 BP 260 EP 266 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA MV829 UT WOS:A1994MV82900005 PM 8106760 ER PT J AU FRANCIS, P LEE, JW HOFFMAN, A PETER, J FRANCESCONI, A BACHER, J SHELHAMER, J PIZZO, PA WALSH, TJ AF FRANCIS, P LEE, JW HOFFMAN, A PETER, J FRANCESCONI, A BACHER, J SHELHAMER, J PIZZO, PA WALSH, TJ TI EFFICACY OF UNILAMELLAR LIPOSOMAL AMPHOTERICIN-B IN TREATMENT OF PULMONARY ASPERGILLOSIS IN PERSISTENTLY GRANULOCYTOPENIC RABBITS - THE POTENTIAL ROLE OF BRONCHOALVEOLAR D-MANNITOL AND SERUM GALACTOMANNAN AS MARKERS OF INFECTION SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID EXPERIMENTAL MURINE ASPERGILLOSIS; INVASIVE ASPERGILLOSIS; ACUTE-LEUKEMIA; FUNGAL-INFECTIONS; DIAGNOSIS; MODEL; MICE; ANTIGENEMIA; AMBISOME; LAVAGE AB A model of primary pulmonary aspergillosis in rabbits was developed to reproduce the persistent levels of profound granulocytopenia and the histopathologic features of bronchopneumonia, vascular invasion, and hemorrhagic infarction encountered in humans. D-mannitol was detectable in bronchoalveolar lavage fluid by gas-liquid chromatography/mass spectroscopy, and galactomannan was measurable in serum by latex agglutination immunoassay. A pharmacokinetically distinctive unilamellar vesicle formulation of liposomal amphotericin B, 5 mg/kg/day intravenously, compared with high-dose conventional desoxycholate amphotericin B, 1 mg/kg/day intravenously, was more effective in preventing nephrotoxicity, increasing survival, reducing the number of viable organisms, and decreasing tissue injury due to Aspergillus organisms. Thus, D-mannitol in lavage fluid and galactomannan in serum may be useful markers of pulmonary aspergillosis, and liposomal amphotericin B was significantly more effective and safer than desoxycholate amphotericin B for treatment of pulmonary aspergillosis in profoundly granulocytopenic rabbits. C1 NCI,PEDIAT BRANCH,INFECT DIS SECT,BETHESDA,MD 20892. WARREN GRANT MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BETHESDA,MD. NIH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,SURG & RADIOL BRANCH,BETHESDA,MD. NR 56 TC 143 Z9 146 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB PY 1994 VL 169 IS 2 BP 356 EP 368 PG 13 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA MV829 UT WOS:A1994MV82900019 PM 8106769 ER PT J AU JACOBSON, MA BESCH, CL CHILD, C HAFNER, R MATTS, JP MUTH, K WENTWORTH, DN NEATON, JD ABRAMS, D RIMLAND, D PEREZ, G GRANT, IH SARAVOLATZ, LD BROWN, LS DEYTON, L AF JACOBSON, MA BESCH, CL CHILD, C HAFNER, R MATTS, JP MUTH, K WENTWORTH, DN NEATON, JD ABRAMS, D RIMLAND, D PEREZ, G GRANT, IH SARAVOLATZ, LD BROWN, LS DEYTON, L TI PRIMARY PROPHYLAXIS WITH PYRIMETHAMINE FOR TOXOPLASMIC ENCEPHALITIS IN PATIENTS WITH ADVANCED HUMAN-IMMUNODEFICIENCY-VIRUS DISEASE - RESULTS OF A RANDOMIZED TRIAL SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; TRIMETHOPRIM-SULFAMETHOXAZOLE; AEROSOLIZED PENTAMIDINE; AIDS; GONDII; CLINDAMYCIN; EXPERIENCE; SURVIVAL; INVIVO; MODELS AB Pyrimethamine, 25 mg thrice weekly, was evaluated as primary prophylaxis for toxoplasmic encephalitis (TE) in a double-blind, randomized clinical trial in patients with human immunodeficiency virus (HIV) disease, absolute CD4 lymphocyte count of <200/mu L (or prior AIDS-defining opportunistic infection), and the presence of serum Ige to Toxoplasma gondii. Leucovorin was coadministered only for hematologic toxicity. There was a significantly higher death rate among patients receiving pyrimethamine (relative risk [RR], 2.5; 95% confidence interval [CI], 1.3-4.8; P = .006), even after adjusting for factors predictive of survival. The TE event rate was low in both treatment groups (not significant). Only 1 of 218 patients taking trimethoprim-sulfamethoxazole but 7 of 117 taking aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia developed TE (adjusted RR for the trimethoprim-sulfamethoxazole group, 0.16; 95% CI, 0.01-1.79; P = .14). Thus, for HIV-infected patients receiving trimethoprim-sulfamethoxazole, additional prophylaxis for TE appears unnecessary. C1 NIAID,DIV AIDS,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA. SAN FRANCISCO GEN HOSP,MED SERV,SAN FRANCISCO,CA 94110. SAN FRANCISCO COMMUNITY CONSORTIUM,SAN FRANCISCO,CA. TULANE UNIV,NEW ORLEANS,LA. ROW SCI,BETHESDA,MD. UNIV MINNESOTA,SCH PUBL HLTH,DIV BIOSTAT,MINNEAPOLIS,MN 55455. VET AFFAIRS MED CTR,AIDS RES CONSORTIUM ATLANTA,ATLANTA,GA. EMORY UNIV,SCH MED,DEPT MED,ATLANTA,GA. N JERSEY COMMUNITY RES INITIAT,NEWARK,NJ. BRONX LEBANON HOSP CTR,BRONX,NY. ADDICT RES & TREATMENT CORP,BROOKLYN,NY. COLUMBIA UNIV COLL PHYS & SURG,HARLEM HOSP,DEPT MED,BROOKLYN,NY. HENRY FORD HOSP,DETROIT,MI. NR 38 TC 58 Z9 58 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB PY 1994 VL 169 IS 2 BP 384 EP 394 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA MV829 UT WOS:A1994MV82900022 PM 8106772 ER PT J AU LAL, RB OWEN, SM RUDOPH, D LEVINE, PH AF LAL, RB OWEN, SM RUDOPH, D LEVINE, PH TI SEQUENCE VARIATION WITHIN THE IMMUNODOMINANT EPITOPE-CODING REGION FROM THE EXTERNAL GLYCOPROTEIN OF HUMAN T-LYMPHOTROPIC VIRUS TYPE-II IN ISOLATES FROM SEMINOLE INDIANS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID CELL LEUKEMIA AB Western blot analysis of 16 serum specimens from Seminole Indians demonstrated that 14 reacted with the type-specific recombinant epitope (rgp46(II+)) of human T lymphotropic virus type II (HTLV-II), whereas the remaining 2 specimens did not (rgp46(II-)). Both rgp46(II-) specimens demonstrated presence of HTLV-II genome by polymerase chain reaction analysis. Culture of 1 of these specimens demonstrated presence of type C retrovirus particles by electron microscopy, and p24(gag) antigens were detectable in culture supernatant. Nucleotide sequence analysis of 557 bp in the env gene (position 5405-5961) from 2 each of the rgp46(II-) and rgp46(II+) specimens demonstrated sequence conservation in the rgp46(II) epitope (K-55(162-205)). Thus, lack of immune reactivity to rgp46 is not due to sequence variation within this epitope. This observation suggests that immunodominant env epitopes may not be universally recognized. Therefore, specimens with p24(gag) and r21e(env) reactivity in modified Western blot assays should be further tested by more sensitive techniques. C1 NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD. RP LAL, RB (reprint author), CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,RETROVIRUS DIS BRANCH,ATLANTA,GA 30329, USA. NR 15 TC 9 Z9 9 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB PY 1994 VL 169 IS 2 BP 407 EP 411 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA MV829 UT WOS:A1994MV82900026 PM 7508969 ER PT J AU VOELLER, D KOVACS, J ANDRAWIS, V CHU, E MASUR, H ALLEGRA, C AF VOELLER, D KOVACS, J ANDRAWIS, V CHU, E MASUR, H ALLEGRA, C TI INTERACTION OF PNEUMOCYSTIS-CARINII DIHYDROPTEROATE SYNTHASE WITH SULFONAMIDES AND DIAMINODIPHENYL SULFONE (DAPSONE) SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID ACQUIRED IMMUNODEFICIENCY SYNDROME; TOXOPLASMA-GONDII; DRUGS; PNEUMONIA; DIHYDROFOLATE; INHIBITION AB Dihydropteroate synthase is the target enzyme for the sulfonamide compounds, which are the mainstay of therapy for Pneumocystis carinii pneumonia, a common infection in patients with impaired immunity. The stability of this enzyme, its kinetic constants with respect to substrates, and the 50% inhibitory concentration (IC50) of several sulfonamides and the sulfone dapsone have been characterized using both cell-free and intact organism assay systems. Stability of the enzyme is dependent on storage temperature, reducing reagents, and to a lesser extent, protease inhibitors. The sulfonamides sulfadiazine and sulfamethoxazole were found to be highly potent inhibitors of P. carinii dihydropteroate synthase with IC(50)s of 0.42 and 0.71 mu M, respectively. Dapsone had equivalent potency when compared with the most potent sulfonamides tested in both assay systems. Data suggest that sulfamethoxazole, sulfadiazine, and dapsone may represent equivalent choices as P. carinii dihydropteroate synthase inhibitors, assuming an equivalent in vivo drug exposure can be achieved. C1 NCI,NATL NAVAL MED CTR,NCI NAVY MED ONCOL BRANCH,BETHESDA,MD 20889. NIH,BETHESDA,MD 20892. NR 15 TC 23 Z9 23 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB PY 1994 VL 169 IS 2 BP 456 EP 459 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA MV829 UT WOS:A1994MV82900038 PM 8106784 ER PT J AU HEARING, VJ KOBAYASHI, T URABE, K POTTERF, B KAMEYAMA, K AF HEARING, VJ KOBAYASHI, T URABE, K POTTERF, B KAMEYAMA, K TI THE CHARACTERISTICS OF BIOLOGICAL MELANINS ARE INFLUENCED AT MULTIPLE POINTS IN THE MELANOGENIC PATHWAY SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIH,CELL BIOL LAB,BETHESDA,MD 20892. MED CTR HOSP,KITASATO INST,KITAMOTO,SAITAMA 364,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD FEB PY 1994 VL 102 IS 2 BP 266 EP 266 PG 1 WC Dermatology SC Dermatology GA MW285 UT WOS:A1994MW28500040 ER PT J AU ISAKOV, N WANGE, RL SAMELSON, LE AF ISAKOV, N WANGE, RL SAMELSON, LE TI THE ROLE OF TYROSINE KINASES AND PHOSPHOTYROSINE-CONTAINING RECOGNITION MOTIFS IN REGULATION OF THE T-CELL-ANTIGEN RECEPTOR-MEDIATED SIGNAL-TRANSDUCTION PATHWAY SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE SH2; SH3; TAM; TYROSINE PHOSPHORYLATION; T CELL ACTIVATION ID AMINO-TERMINAL DOMAIN; PROTEIN-KINASE; ZETA-CHAIN; C-SRC; PHOSPHOLIPASE C-GAMMA-1; CYTOPLASMIC TAIL; MOLECULAR-CLONING; CROSS-LINKING; BINDING-SITE; CD4 RECEPTOR AB T cell-mediated immune responses are initiated by interaction of antigen bound to a glycoprotein encoded by the major histocompatibility complex with the T cell antigen receptor (TCR). These recognition and binding steps are followed by multiple intracellular biochemical events. The earliest event detected is an increase in intracellular protein tyrosine phosphorylation that involves a complex interaction of tyrosine kinases and phosphatases. Subsequently, one observes an increase in protein serine/threonine phosphorylation, phospholipid hydrolysis, and changes in intracellular Ca2+ levels. These and other biochemical changes lead to cell proliferation, differentiation, and acquisition of effector functions. While binding of extracellular growth factors to receptors containing cytoplasmic protein tyrosine kinase (PTK) domains induces direct activation of their kinase activity, the multichain TCR lacks an intrinsic kinase domain and therefore represents a distinct type of receptor. It transduces signals via the interaction with, and activation of, nbn-receptor PTKs. Recent efforts directed at defining the TCR-linked signaling pathways have provided insight into the regulatory role of three PTKs, and the functional importance of some unique protein motifs in both TCR subunits and PTKs, which mediate critical protein-protein interactions in this pathway. C1 BEN GURION UNIV NEGEV,CANC RES CTR,BEER SHEVA,ISRAEL. BEN GURION UNIV NEGEV,FAC HLTH SCI,DEPT MICROBIOL & IMMUNOL,IL-84105 BEER SHEVA,ISRAEL. RP ISAKOV, N (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BLDG 18T,ROOM 101,BETHESDA,MD 20892, USA. RI ISAKOV, NOAH/F-1659-2012 NR 94 TC 52 Z9 52 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD FEB PY 1994 VL 55 IS 2 BP 265 EP 271 PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA MV294 UT WOS:A1994MV29400020 PM 7507972 ER PT J AU KEEGAN, AD PIERCE, JH AF KEEGAN, AD PIERCE, JH TI THE INTERLEUKIN-4 RECEPTOR - SIGNAL-TRANSDUCTION BY A HEMATOPOIETIN RECEPTOR SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE TYROSINE PHOSPHORYLATION; CYTOKINES; CELL PROLIFERATION ID STIMULATORY FACTOR-I; PROTEIN TYROSINE PHOSPHORYLATION; MURINE LYMPHOCYTES-B; CELL GROWTH-FACTOR; HIGH-AFFINITY; BETA-CHAIN; ERYTHROPOIETIN RECEPTOR; MOLECULAR-CLONING; KINASE-ACTIVITY; IL-2 RECEPTOR AB Over the last several years, the receptors for numerous cytokines have been molecularly characterized. Analysis of their amino acid sequences shows that some of these receptors bear certain motifs in their extracellular domains that define a family of receptors called the Hematopoietin receptor superfamily [1-3]. Significant advances in characterizing the structure, function, and mechanisms of signal transduction have been made for several members of this family. The purpose of this review is to discuss the recent advances made for one of the family members, the interleukin (IL) 4 receptor. Other receptor systems have recently been reviewed elsewhere [4-7]. The IL-4 receptor consists of, at the minimum, the cloned 140 kDa IL-4-binding chain with the potential for associating with other chains. The IL-4 receptor transduces its signal by activating a tyrosine kinase that phosphorylates cellular substrates, including the receptor itself, and the 170 kDa substrate called 4PS. Phosphorylated 4PS interacts with the SH2 domain of the enzyme PI-3'-kinase and increases its enzymatic activity. These early events in the IL-4: receptor initiated signaling pathway may trigger a series of signals that will ultimately lead to an IL-4 specific biologic outcome. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP KEEGAN, AD (reprint author), NIAID,IMMUNOL LAB,BLDG 10,RM 11N311,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 74 TC 21 Z9 21 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD FEB PY 1994 VL 55 IS 2 BP 272 EP 279 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA MV294 UT WOS:A1994MV29400021 PM 7507973 ER PT J AU BAX, A GRZESIEK, S GRONENBORN, AM CLORE, GM AF BAX, A GRZESIEK, S GRONENBORN, AM CLORE, GM TI ISOTOPE-FILTERED 2D HOHAHA SPECTROSCOPY OF A PEPTIDE-PROTEIN COMPLEX USING HETERONUCLEAR HARTMANN-HAHN DEPHASING SO JOURNAL OF MAGNETIC RESONANCE SERIES A LA English DT Note ID H-1-NMR SPECTRA; CROSS POLARIZATION; CALMODULIN; LIQUIDS; NMR; IDENTIFICATION; COHERENCE; H-1 RP BAX, A (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 21 TC 34 Z9 34 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1064-1858 J9 J MAGN RESON SER A JI J. Magn. Reson. Ser. A PD FEB PY 1994 VL 106 IS 2 BP 269 EP 273 DI 10.1006/jmra.1994.1038 PG 5 WC Physics, Atomic, Molecular & Chemical SC Physics GA MX197 UT WOS:A1994MX19700021 ER PT J AU GOLDSTEIN, S ELKINS, WR LONDON, WT HAHN, A GOEKEN, R MARTIN, JE HIRSCH, VM AF GOLDSTEIN, S ELKINS, WR LONDON, WT HAHN, A GOEKEN, R MARTIN, JE HIRSCH, VM TI IMMUNIZATION WITH WHOLE INACTIVATED VACCINE PROTECTS FROM INFECTION BY SIV GROWN IN HUMAN BUT NOT MACAQUE CELLS SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article; Proceedings Paper CT 11th Annual Meeting on Nonhuman Primate Models for AIDS VI CY SEP 19-22, 1993 CL UNIV WISCONSIN MADISON, WISCONSIN REG PRIMATE RES CTR, MADISON, WI HO UNIV WISCONSIN MADISON, WISCONSIN REG PRIMATE RES CTR DE AIDS; ANTI-CELL ANTIBODIES; SIMIAN IMMUNODEFICIENCY VIRUS ID SIMIAN IMMUNODEFICIENCY VIRUS; CONFERS PROTECTION; CHALLENGE AB Homologous SIV(sm) stocks were generated by passage of a macaque isolate of SIV(sm) (SIV(sm/E660)) in human CEM x 174 cells or macaque peripheral blood mononuclear cells. Macaques were immunized with whole inactivated SIV vaccine consisting of virus generated by transfection of CEM x 174 cells with the SIV(smH4) clone and were challenged with either cell-free stock. Only vaccinees challenged with virus generated in human cells were protected from infection. This confirms the species-specificity of whole inactivated vaccine-mediated protection. C1 NIAID,INFECT DIS LAB,IMMUNODEFICIENCY VIRUSES SECT,TWINBROOK FACIL 2,12441 PARKLAWN DR,ROCKVILLE,MD 20852. GEORGETOWN UNIV,DEPT MICROBIOL,DIV MOLEC VIROL & IMMUNOL,ROCKVILLE,MD. NR 18 TC 36 Z9 36 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD FEB-MAY PY 1994 VL 23 IS 2-3 BP 75 EP 82 PG 8 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA NX987 UT WOS:A1994NX98700003 PM 7966237 ER PT J AU BENVENISTE, RE ROODMAN, ST HILL, RW KNOTT, WB RIBAS, JL LEWIS, MG EDDY, GA AF BENVENISTE, RE ROODMAN, ST HILL, RW KNOTT, WB RIBAS, JL LEWIS, MG EDDY, GA TI INFECTIVITY OF TITERED DOSES OF SIMIAN IMMUNODEFICIENCY VIRUS CLONE E11S INOCULATED INTRAVENOUSLY INTO RHESUS MACAQUES (MACACA-MULATTA) SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article; Proceedings Paper CT 11th Annual Meeting on Nonhuman Primate Models for AIDS VI CY SEP 19-22, 1993 CL UNIV WISCONSIN MADISON, WISCONSIN REG PRIMATE RES CTR, MADISON, WI HO UNIV WISCONSIN MADISON, WISCONSIN REG PRIMATE RES CTR DE AIDS; VACCINES; ANIMAL INFECTIOUS DOSE; SIV ID RECOMBINANT VACCINIA VIRUS; SIV INFECTION; ENVELOPE GLYCOPROTEINS; SUBUNIT VACCINES; PROTECTION; MONKEYS; FASCICULARIS; DISEASE; IMMUNIZATION; TRANSMISSION AB The macaque infectious dose (MID) of a single-cell clone of simian immunodeficiency virus isolated from a pig-tailed macaque (SIV/Mne clone E11S) was determined in rhesus macaques (Macaca mulatta). Twenty-one macaques were inoculated with 10-fold dilutions of the virus stock (three or four animals per dose). The virologic and clinical status of these animals was monitored for 26 weeks. The 25% MID (MID25) occurred at a 10(5)-fold dilution of the viral stock. C1 ST LOUIS UNIV,SCH MED,ST LOUIS,MO 63104. NCI,FCRDC,PROGRAM RESOURCES INC,DYNCERP,FREDERICK,MD 21701. HENRY M JACKSON FDN,RES LAB,ROCKVILLE,MD. RP BENVENISTE, RE (reprint author), NCI,VIRAL CARCINOGENESIS LAB,BLDG 560,FREDERICK,MD 21702, USA. NR 21 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 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD FEB-MAY PY 1994 VL 23 IS 2-3 BP 83 EP 88 PG 6 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA NX987 UT WOS:A1994NX98700004 PM 7966238 ER PT J AU NOVEMBRE, FJ SAUCIER, MM HIRSCH, VM JOHNSON, PR MCCLURE, HM AF NOVEMBRE, FJ SAUCIER, MM HIRSCH, VM JOHNSON, PR MCCLURE, HM TI VIRAL GENETIC-DETERMINANTS IN SIV(SMMPBJ) PATHOGENESIS SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article; Proceedings Paper CT 11th Annual Meeting on Nonhuman Primate Models for AIDS VI CY SEP 19-22, 1993 CL UNIV WISCONSIN MADISON, WISCONSIN REG PRIMATE RES CTR, MADISON, WI HO UNIV WISCONSIN MADISON, WISCONSIN REG PRIMATE RES CTR DE LENTIVIRUS; ACUTE DISEASE; GAG, GP40 ID SIMIAN IMMUNODEFICIENCY VIRUS; RHESUS-MONKEYS; TRANSMEMBRANE PROTEIN; SOOTY MANGABEYS; MACAQUE MONKEYS; MATRIX PROTEIN; MATURE VIRIONS; HIV-INFECTION; NEF GENE; AIDS AB A variant simian immunodeficiency virus (SIV) from sooty mangabeys, SIV(smmPBj), induces an acutely lethal disease in pigtailed macaques (Macaca nemestrina). This study further characterizes the viral genetic determinants involved in this acutely lethal disease. We have generated chimeric molecular clones constructed between SIV(smmpBj) and either SIV(smH4) or SIV(smm9) to analyze the role of the 5' half of the genome and the envelope gene in the induction of acute disease. These studies suggest that the gag and gp40 of SIV(smmPBj) are required for the development of lethal disease, and an additional determinant in the central regulatory gene region of the SIV(smmpBj) genome is also required. C1 EMORY UNIV,DEPT PATHOL,ATLANTA,GA 30322. NIAID,INFECT DIS LAB,ROCKVILLE,MD. OHIO STATE UNIV,CHILDRENS HOSP,DEPT PEDIAT,COLUMBUS,OH 43210. RP NOVEMBRE, FJ (reprint author), EMORY UNIV,YERKES REG PRIMATE RES CTR,DIV PATHOBIOL & IMMUNOBIOL,954 N GATEWOOD RD,ATLANTA,GA 30322, USA. RI Johnson, Philip/A-6892-2009 FU NCRR NIH HHS [RR-00165] NR 33 TC 19 Z9 19 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD FEB-MAY PY 1994 VL 23 IS 2-3 BP 136 EP 145 PG 10 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA NX987 UT WOS:A1994NX98700012 PM 7966228 ER PT J AU GARTNER, S LIU, YL POLONIS, V LEWIS, MG ELKINS, WR HUNTER, EA MIAO, J CORTS, KJ EDDY, GA AF GARTNER, S LIU, YL POLONIS, V LEWIS, MG ELKINS, WR HUNTER, EA MIAO, J CORTS, KJ EDDY, GA TI ADAPTATION OF HIV-1 TO PIGTAILED MACAQUES SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article; Proceedings Paper CT 11th Annual Meeting on Nonhuman Primate Models for AIDS VI CY SEP 19-22, 1993 CL UNIV WISCONSIN MADISON, WISCONSIN REG PRIMATE RES CTR, MADISON, WI HO UNIV WISCONSIN MADISON, WISCONSIN REG PRIMATE RES CTR DE HIV; INFECTION; MONKEYS ID HUMAN-IMMUNODEFICIENCY-VIRUS; HTLV-III; CYNOMOLGUS MACAQUES; MACACA-FASCICULARIS; T-CELL; INFECTION; MONKEYS; RHESUS; RETROVIRUSES; LYMPHOCYTES AB In vitro infectivity experiments were performed to assess the susceptibility of cells from various monkey species to HIV-1. T lymphocytes from pigtailed macaques, but not those from rhesus or cynomolgus monkeys, were susceptible to infection, but virus expression was limited. The majority of HIV-1 isolates were unable to productively infect pigtailed macaque cells. Inoculation of autologous, HIV-1 expressing cells led to establishment of persistent infection in pigtailed macaques as evidenced by recovery of infectious virus and development of virus-specific antibody responses. C1 WALTER REED ARMY INST RES,DEPT RETROVIRAL RES,DIV RETROVIROL,ROCKVILLE,MD. NIAID,BETHESDA,MD 20892. RP GARTNER, S (reprint author), HENRY M JACKSON FDN,RES LAB,1500 E GUDE DR,ROCKVILLE,MD 20850, USA. NR 27 TC 15 Z9 16 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD FEB-MAY PY 1994 VL 23 IS 2-3 BP 155 EP 163 PG 9 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA NX987 UT WOS:A1994NX98700015 PM 7966231 ER PT J AU TSAI, CC FOLLIS, KE GRANT, R SABO, A NOLTE, R BARTZ, C BISCHOFBERGER, N BENVENISTE, R AF TSAI, CC FOLLIS, KE GRANT, R SABO, A NOLTE, R BARTZ, C BISCHOFBERGER, N BENVENISTE, R TI COMPARISON OF THE EFFICACY OF AZT AND PMEA TREATMENT AGAINST ACUTE SIV(MNE) INFECTION IN MACAQUES SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article; Proceedings Paper CT 11th Annual Meeting on Nonhuman Primate Models for AIDS VI CY SEP 19-22, 1993 CL UNIV WISCONSIN MADISON, WISCONSIN REG PRIMATE RES CTR, MADISON, WI HO UNIV WISCONSIN MADISON, WISCONSIN REG PRIMATE RES CTR DE ANTIVIRAL DRUGS; MONKEYS; SIV; HIV ID SIMIAN IMMUNODEFICIENCY VIRUS; AIDS-RELATED COMPLEX; RHESUS-MONKEYS; REPLICATION INVITRO; SIV INFECTION; THERAPY; 3'-AZIDO-3'-DEOXYTHYMIDINE; ZDV; 9-(2-PHOSPHONYLMETHOXYETHYL)ADENINE; AZIDOTHYMIDINE AB The antiretroviral drugs azidothymidine (AZT) and 9-(-2-phosphonyl-methoxyethyl)adenine (PMEA) were individually tested for prevention of simian immunodeficiency ViruS (SIV(mne)) infection in macaques (Macaca fascicularis). Macaques were pretreated with either drug before inoculation with SIV(mne), and drug treatment was continued for four weeks. The virus, antibody, and clinical status of the macaques was monitored for up to 36 weeks following inoculation. While AZT prophylaxis resulted in reduced virus load in some macaques, PMEA prophylaxis was highly efficacious in preventing acute SIV(mne) infection. C1 GILEAD SCI,FOSTER CITY,CA. NCI,FREDERICK,MD 21701. RP TSAI, CC (reprint author), UNIV WASHINGTON,REG PRIMATE RES CTR,PRIMATE FIELD STN,MEDICAL LAKE,WA 99022, USA. FU NCRR NIH HHS [RR00166]; NIAID NIH HHS [NIAID NO1-AI-15120] NR 26 TC 24 Z9 25 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD FEB-MAY PY 1994 VL 23 IS 2-3 BP 175 EP 183 PG 9 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA NX987 UT WOS:A1994NX98700017 PM 7966233 ER PT J AU HAMMER, JA AF HAMMER, JA TI THE STRUCTURE AND FUNCTION OF UNCONVENTIONAL MYOSINS - A REVIEW SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Review ID I HEAVY-CHAIN; ACANTHAMOEBA MYOSIN; BRUSH-BORDER; CELL-LINE; DROSOPHILA-MELANOGASTER; GENE ENCODES; V MYOSIN; CALMODULIN; IDENTIFICATION; LOCALIZATION RP HAMMER, JA (reprint author), NHLBI,CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 89 TC 62 Z9 62 U1 1 U2 1 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PD FEB PY 1994 VL 15 IS 1 BP 1 EP 10 DI 10.1007/BF00123827 PG 10 WC Cell Biology SC Cell Biology GA MV995 UT WOS:A1994MV99500001 PM 8182104 ER PT J AU HOKE, SH COOKS, RG CHANG, CJ KELLY, RC QUALLS, SJ ALVARADO, B MCGUIRE, MT SNADER, KM AF HOKE, SH COOKS, RG CHANG, CJ KELLY, RC QUALLS, SJ ALVARADO, B MCGUIRE, MT SNADER, KM TI DETERMINATION OF TAXANES IN TAXUS-BREVIFOLIA EXTRACTS BY TANDEM MASS-SPECTROMETRY AND HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID TAXOL; SEPARATION; CEPHALOMANNINE AB A tandem mass spectrometric (ms/ms) method using desorption chemical ionization is described for the quantitation of taxol [1], cephalomannine [2], and baccatin III [3] found in Taxus brevifolia bark and needle extracts. A parent ion scan was used to simultaneously determine the weight percentages of 1-3 in bark and needle samples by the method of standard addition. In an alternative experiment, the concentration oil in the same samples was determined by ms/ms using trideuterated 10-acetyltaxol [7a] as an internal standard. High-performance liquid chromatography (hplc) was also used to determine the weight, percentages of 1-3 in the same T. brevifolia bark and needle extracts with an external standard. The ms/ms method of quantitation by internal standard is the best overall method of analysis examined. With this method, 1 was quantitated in the T. Brevifolia extracts at the low picomole level with a relative standard deviation of 17% or better for all samples analyzed with an analysis time of less than five min per sample. The precision, level of quantitation, and speed of analysis of the three methods of taxane quantitation are compared. C1 PURDUE UNIV,DEPT CHEM,W LAFAYETTE,IN 47907. PURDUE UNIV,DEPT MED CHEM & PHARMACOGNOSY,W LAFAYETTE,IN 47907. UPJOHN CO,MED CHEM RES,KALAMAZOO,MI 49001. NCI,FREDERICK CANC RES & DEV CTR,DYNCORP INC,PROGRAM RESOURCES,FREDERICK,MD 21702. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,NAT PROD BRANCH,FREDERICK,MD 21702. RI Cooks, R/G-1051-2015 OI Cooks, R/0000-0002-9581-9603 FU NCI NIH HHS [R01 CA55118] NR 36 TC 24 Z9 25 U1 0 U2 1 PU AMER SOC PHARMACOGNOSY PI CINCINNATI PA LLOYD LIBRARY & MUSEUM 917 PLUM ST, CINCINNATI, OH 45202 SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD FEB PY 1994 VL 57 IS 2 BP 277 EP 286 DI 10.1021/np50104a013 PG 10 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA NA314 UT WOS:A1994NA31400013 PM 7909835 ER PT J AU HOUGH, C FUKAMAUCHI, F CHUANG, DM AF HOUGH, C FUKAMAUCHI, F CHUANG, DM TI REGULATION OF BETA-ADRENERGIC-RECEPTOR MESSENGER-RNA IN RAT C-6 GLIOMA-CELLS IS SENSITIVE TO THE STATE OF MICROTUBULE ASSEMBLY SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE BETA-ADRENERGIC RECEPTORS; MESSENGER-RNA; CYCLIC AMP; MICROTUBULES; C-6 GLIOMA CELLS ID MESSENGER-RNA; ADENYLATE-CYCLASE; DOWN-REGULATION; CYCLIC-AMP; ENDOPLASMIC-RETICULUM; MEMBRANE; BINDING; INTERNALIZATION; CYTOSKELETON; COLCHICINE AB Microtubule disrupter, colchicine, and microtubule stabilizer, taxol, were used to determine whether microtubules play a role in beta-adrenergic receptor mRNA homeostasis and agonist-induced down-regulation in C-6 glioma cells. Colchicine treatment had significant, differential, time-dependent effects on constitutive beta(1)- and beta(2)-adrenergic receptor mRNA levels. These effects stemmed from the action of colchicine on microtubules, because beta-lumicolchicine, an inactive isomer, had no effect, and nocodazole, a structurally unrelated microtubule disrupter, had similar effects. Colchicine treatment had little effect on the total number of beta-adrenergic receptor binding sites as measured by (-)-[I-125]iodopindolol binding, but did alter the relative proportion of beta(1)- and beta(2)-adrenergic receptor subtypes. Colchicine also had no effect on basal cyclic AMP levels. In contrast to colchicine, taxol treatment had little long-term effect on either beta(1)- or beta(2)-adrenergic receptor mRNA levels. Taxol antagonized the effects of colchicine on total binding and mRNA levels. Taxol treatment increased basal cyclic AMP levels fourfold and potentiated (-)-isoproterenol-induced cyclic AMP production. Colchicine pretreatment completely inhibited (-)-isoproterenol-induced down-regulation of beta(1)-adrenergic receptor mRNA, but not that of beta(2)-adrenergic receptor mRNA. Taxol pretreatment had little effect on isoproterenol-induced beta-adrenergic receptor mRNA down-regulation. Colchicine pretreatment also attenuated isoproterenol-induced receptor down-regulation and inhibited agonist-stimulated cyclic AMP production. These effects of colchicine were antagonized by taxol. Whereas the effects of taxol and colchicine on isoproterenol-induced down-regulation of beta-adrenergic receptor mRNA are consistent with their effects on cyclic AMP production, those of colchicine in the absence of stimulation must involve other mechanisms. The data demonstrate that the state of microtubule assembly can affect cyclic AMP levels, beta(1)- and beta(2)-adrenergic receptor mRNA, and binding site levels in C-6 glioma cells. C1 NIMH,BIOL PSYCHIAT BRANCH,MOLEC NEUROBIOL SECT,BETHESDA,MD 20892. NR 31 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD FEB PY 1994 VL 62 IS 2 BP 421 EP 430 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA MT817 UT WOS:A1994MT81700002 PM 7905023 ER PT J AU PENNYPACKER, KR MCMILLIAN, MK DOUGLASS, J HONG, JS AF PENNYPACKER, KR MCMILLIAN, MK DOUGLASS, J HONG, JS TI ONTOGENY OF KAINATE-INDUCED GENE-EXPRESSION IN RAT HIPPOCAMPUS SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE TRANSCRIPTION FACTOR; AP-1 DNA BINDING; KAINATE; SEIZURE ACTIVITY; HIPPOCAMPUS; OPIOID PEPTIDE GENES ID ENKEPHALIN-LIKE IMMUNOREACTIVITY; IMMEDIATE-EARLY GENES; C-FOS; DENTATE GYRUS; MESSENGER-RNA; RECURRENT SEIZURES; STATUS EPILEPTICUS; DYNORPHIN-LIKE; MOSSY FIBERS; CYCLIC AMP AB The ontogeny of kainate induction of AP-I mRNAs, proteins, and DNA binding activities was examined in the rat hippocampus. In addition, kainate induction of preproenkephalin and preprodynorphin mRNAs was examined; these genes have been shown to be induced by kainate and have been suggested to be targets of AP-1 regulation in adult rat hippocampus. Despite producing seizures at postnatal day (P) 7, kainate failed to induce AP-I or opiate gene expression and did not increase AP-I DNA binding activity at this age. Basal levels of AP-I and opiate mRNAs were low in P7 hippocampus. Basal levels of c-jun protein and AP-I DNA binding activity were elevated in the P7 hippocampus, to values greater than induced levels in adult hippocampus. Furthermore, AP-I DNA binding in P7 hippocampal nuclear extract was unaffected by antibodies against fos-related antigens, in contrast to hippocampal extracts from the older rats examined. At P14, induction of AP-I and preproenkephalin (but not preprodynorphin) mRNAs was observed with kainate treatment, but the time course for inductions was delayed relative to kainate inductions in the adult hippocampus. At P21, responses to kainate were similar to the adult response. Unlike in adult hippocampus, seizure activity caused by kainate treatment does not increase the transcription factor and opioid peptide gene expression in the hippocampi of P7 rats. C1 OREGON HLTH SCI UNIV,VOLLUM INST,PORTLAND,OR 97201. RP PENNYPACKER, KR (reprint author), NIEHS,INTEGRAT BIOL LAB,MD E1-01,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Pennypacker, Keith/I-5092-2012 NR 38 TC 29 Z9 29 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD FEB PY 1994 VL 62 IS 2 BP 438 EP 444 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA MT817 UT WOS:A1994MT81700004 PM 8294905 ER PT J AU WITT, DM INSEL, TR AF WITT, DM INSEL, TR TI INCREASED FOS EXPRESSION IN OXYTOCIN NEURONS FOLLOWING MASCULINE SEXUAL-BEHAVIOR SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE VASOPRESSIN; IMMEDIATE EARLY GENES; PENILE REFLEXES ID CORTICOTROPIN-RELEASING-FACTOR; C-FOS; SPINAL-CORD; MALE-RATS; PARAVENTRICULAR NUCLEUS; PENILE ERECTION; MAGNOCELLULAR NEURONS; OLFACTORY-BULB; NERVOUS-SYSTEM; VASOPRESSIN AB Induction of the c-fos protein product (Fos) was used to immunocytochemically identity oxytocin (OT) neurons that may be activated during copulatory interactions. Fos induction was quantified in sexually-experienced male rats after either (a) exposure to a testing arena recently vacated by an estrous female, (b) copulatory interactions such as mounting and intromission without ejaculation, or (c) mounting and intromissions culminating in ejaculation. In the parvocellular regions of the paraventricular nucleus of the hypothalamus (PVN), the number of neurons expressing Fos increased following either intromission (53%) or ejaculation (124%). Significant, but less striking, increases in the number of cells expressing Fos were noted in magnocellular regions of the PVN where intromission resulted in a 13% increase and ejaculation in a 49% increase in Fos. The number of perikarya immunoreactive for OT and AVP did not differ as a function of increasing sexual contacts. In control (novel arena) males, 33-73% of the Fos labeling occurred in OT cells. Sexual interactions did not enhance the number of double-labeled cells in most parvocellular regions. However, in lateral parvocellular regions located in the most caudal aspects of the PVN, 31% of the Fos-positive cells occurred in OT neurons in ejaculated males, while in control males none of the OT cells were double-labeled. This PVN subdivision is known to consist of neurons that project to the brain stem and spinal cord at lumbar levels which contain motor neurons that regulate penile reflexes. The present data suggest a possible neurochemical circuit which incorporates oxytocinergic neurons in the mediation of masculine sexual responses. C1 NIMH,NEUROPHYSIOL LAB,POOLESVILLE,MD 20837. NR 43 TC 73 Z9 73 U1 2 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD FEB PY 1994 VL 6 IS 1 BP 13 EP 18 DI 10.1111/j.1365-2826.1994.tb00549.x PG 6 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA MX048 UT WOS:A1994MX04800004 PM 8025564 ER PT J AU MAZOROW, DL SIMPKINS, CO MILLAR, DB AF MAZOROW, DL SIMPKINS, CO MILLAR, DB TI BETA-ENDORPHIN MODULATES CALCIUM-CHANNEL ACTIVITY IN HUMAN NEUTROPHILS SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE BETA-ENDORPHIN; NEUTROPHILS; CALCIUM CHANNEL ID POTASSIUM-CHANNEL; CYTOSOLIC CALCIUM; DISTINCT; RELEASE; RECEPTOR; CELLS; BRAIN; FLUX; K+ AB 10(-6) M n-formyl-methionyl-leucyl-phenylalanine (FMLP) stimulated Ca2+ flux in human neutrophils is characterized by a profile composed of two peaks of different amplitude and breadth. beta-Endorphin inhibited the magnitude and modulated the kinetics of the second peak in a manner which was dose-dependent and could reflect either negative cooperativity or heterogeneity of binding sites. The second peak arises from calcium channel activity since in the presence of nifedipine or EGTA it was not evident while the first peak was reduced about 24%. Similarly, at 15 degrees C, where we were unable to detect any channel activity, the first peak was diminished by 35% and beta-endorphin had no detectable effect on this peak. These results led us to conclude that the first peak is chiefly composed of Ca2+ recruited from cytosolic stores which are relatively insensitive to the above treatments and a smaller fraction of calcium originating in calcium channel activity. Hence, we reason that beta-endorphin modulates only the calcium ion flux arising from calcium channel function. C1 NEW IDEAS CO,ROCKVILLE,MD 20852. UNIV MARYLAND,SCH MED,DEPT SURG,BALTIMORE,MD 21201. ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. NR 35 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD FEB PY 1994 VL 50 IS 1 BP 77 EP 83 DI 10.1016/0165-5728(94)90217-8 PG 7 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA MV467 UT WOS:A1994MV46700011 PM 8300859 ER PT J AU MCINTOSH, AR GRADY, CL UNGERLEIDER, LG HAXBY, JV RAPOPORT, SI HORWITZ, B AF MCINTOSH, AR GRADY, CL UNGERLEIDER, LG HAXBY, JV RAPOPORT, SI HORWITZ, B TI NETWORK ANALYSIS OF CORTICAL VISUAL PATHWAYS MAPPED WITH PET SO JOURNAL OF NEUROSCIENCE LA English DT Article DE STRUCTURAL EQUATION MODELING; HUMAN; SPATIAL VISION; OBJECT VISION; CEREBRAL BLOOD FLOW; NEURAL PATHWAY; PATH ANALYSIS ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL GLUCOSE-METABOLISM; HUMAN EXTRASTRIATE CORTEX; PREFRONTAL CORTEX; SPATIAL VISION; BRAIN-REGIONS; RHESUS-MONKEY; OBJECT; AREAS; 2-DEOXYGLUCOSE AB Brain metabolic mapping techniques, such as positron emission tomography (PET), can provide information about the functional interactions within entire neural systems. With the large quantity of data that can accumulate from a mapping study, a network analysis, which makes sense of the complex interactions among neural elements, is necessary. A network analysis was performed on data obtained from a PET study that examined both the changes in regional cerebral blood flow (rCBF) and interregional correlations among human cortical areas during performance of an object vision (face matching) and spatial vision (dot-location matching) task. Brain areas for the network were selected based on regions showing significant rCBF or interregional correlations between tasks. Anterior temporal and frontal lobe regions were added to the network using a principal components analysis. Interactions among selected regions were quantified with structural equation modeling. In the structural equation models, connections between brain areas were based on known neuroanatomy and the interregional correlations were used to calculate path coefficients representing the magnitude of the influence of each directional path. The combination of the anatomical network and interregional correlations created a functional network for each task. The functional network for the right hemisphere showed that in the object vision task, dominant path influences were among occipitotemporal areas, while in the spatial vision task, occipitoparietal interactions were stronger. The network for the spatial vision task also had a strong feedback path from area 46 to occipital cortex, an effect that was absent in the object vision task. There were strong interactions between dorsal and ventral pathways in both networks. Functional networks for the left hemisphere did not differ between tasks. Networks for the interhemispheric interactions showed that the dominant pathway in the right hemisphere also had stronger effects on homologous left hemisphere areas and are consistent with a hypothesis that intrahemispheric interactions were greater in the right hemisphere in both tasks, and that these influences were transmitted callosally to the left hemisphere. C1 NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. RP MCINTOSH, AR (reprint author), NIA,NEUROSCI LAB,NIH BLDG,ROOM 6C414,BETHESDA,MD 20892, USA. RI McIntosh, Anthony/G-4955-2011 NR 49 TC 327 Z9 329 U1 1 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD FEB PY 1994 VL 14 IS 2 BP 655 EP 666 PG 12 WC Neurosciences SC Neurosciences & Neurology GA MV319 UT WOS:A1994MV31900017 PM 8301356 ER PT J AU PETRALIA, RS YOKOTANI, N WENTHOLD, RJ AF PETRALIA, RS YOKOTANI, N WENTHOLD, RJ TI LIGHT AND ELECTRON-MICROSCOPE DISTRIBUTION OF THE NMDA RECEPTOR SUBUNIT NMDAR1 IN THE RAT NERVOUS-SYSTEM USING A SELECTIVE ANTIPEPTIDE ANTIBODY SO JOURNAL OF NEUROSCIENCE LA English DT Review DE EXCITATORY AMINO ACIDS; ULTRASTRUCTURE; IMMUNOCYTOCHEMISTRY; AMPA; HIPPOCAMPUS; CEREBELLUM ID METHYL-D-ASPARTATE; LONG-TERM POTENTIATION; AMINO-ACID RECEPTORS; METABOTROPIC GLUTAMATE RECEPTOR; EXCITATORY SYNAPTIC CURRENTS; CEREBELLAR PURKINJE-CELLS; MEDIAL VESTIBULAR NUCLEUS; MOLECULAR-CLONING; NORADRENALINE RELEASE; BRAIN-STEM AB NMDA receptors play key roles in synaptic plasticity and neuronal development, and may be involved in learning, memory, and compensation following injury. A polyclonal antibody that recognizes four of seven splice variants of NMDAR1 was made using a C-terminus peptide (30 amino acid residues). NMDAR1 is the major NMDA receptor subunit, found in most or all NMDA receptor complexes. On immunoblots, this antibody labeled a single major band migrating at M(r) = 120,000. The antibody did not cross-react with extracts from transfected cells expressing other glutamate receptor subunits, nor did it label non-neuronal tissues. Immunostained vibratome sections of rat tissue showed labeling in many neurons in most structures in the brain, as well as in the cervical spinal cord, dorsal root and vestibular ganglia, and in pineal and pituitary glands. Staining was moderate to dense in the olfactory bulb, neocortex, striatum, some thalamic and hypothalamic nuclei, the colliculi, and many reticular, sensory, and motor neurons of the brainstem and spinal cord. The densest stained cells included the pyramidal and hilar neurons of the CA3 region of the hippocampus, Purkinje cells of the cerebellum, supraoptic and magnocellular paraventricular neurons of the hypothalamus, inferior olive, red nucleus, lateral reticular nucleus, peripheral dorsal cochlear nucleus, and motor nuclei of the lower brainstem and spinal cord. Ultrastructural localization of immunostaining was examined in the hippocampus, cerebral cortex, and cerebellar cortex. The major staining was in postsynaptic densities apposed by unstained presynaptic terminals with round or mainly round vesicles, and in associated dendrites. The pattern of staining matched that of previous in situ hybridization but differed somewhat from that of binding studies, implying that multiple types of NMDA receptors exist. Comparison with previous studies of localization of other glutamate receptor types revealed that NMDAR1 may colocalize with these other types in many neurons throughout the nervous system. RP PETRALIA, RS (reprint author), NIDCD, NEUROCHEM LAB, BLDG 36, ROOM 5D-08, BETHESDA, MD 20892 USA. NR 141 TC 782 Z9 786 U1 2 U2 22 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD FEB PY 1994 VL 14 IS 2 BP 667 EP 696 PG 30 WC Neurosciences SC Neurosciences & Neurology GA MV319 UT WOS:A1994MV31900018 PM 8301357 ER PT J AU ABI-DARGHAM, A LARUELLE, M SEIBYL, J RATTNER, Z BALDWIN, RM ZOGHBI, SS ZEAPONCE, Y BREMNER, JD HYDE, TM CHARNEY, DS HOFFER, PB INNIS, RB AF ABI-DARGHAM, A LARUELLE, M SEIBYL, J RATTNER, Z BALDWIN, RM ZOGHBI, SS ZEAPONCE, Y BREMNER, JD HYDE, TM CHARNEY, DS HOFFER, PB INNIS, RB TI SPECT MEASUREMENT OF BENZODIAZEPINE RECEPTORS IN HUMAN BRAIN WITH IODINE-123-IOMAZENIL - KINETIC AND EQUILIBRIUM PARADIGMS SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE SPECT; BRAIN; BENZODIAZEPINE RECEPTORS; IODINE-123-IOMAZENIL ID POSITRON EMISSION TOMOGRAPHY; BINDING-SITES; C-11 FLUMAZENIL; QUANTITATIVE-EVALUATION; HUNTINGTONS-DISEASE; I-123 IOMAZENIL; ALZHEIMER-TYPE; RO 15-1788; INVIVO; PET AB Iodine-123-iomazenil binding to benzodiazepine receptors in human brain was measured with SPECT using kinetic and equilibrium methods. Methods: In the kinetic experiments (n = 6), regional time-activity curves after a single bo[us injection of the tracer were fit to a three-compartment model to provide estimates of the rate constants K-1 to k(4). The binding potential (equal to the product of the receptor density and affinity) was derived from the rate constants. In the equilibrium method (n = 8), the tracer bolus injection was followed by a constant tracer infusion to induce a sustained equilibrium state. The regional equilibrium volume of distribution was calculated as the ratio of the regional brain concentration-to-the free parent tracer steady-state plasma concentration. In three experiments, a receptor-saturating dose of flumazenil was injected for direct measurement of the nondisplaceable compartment distribution volume. Results: The kinetic and equilibrium method results were in good agreement in all regions investigated. Iodine-125-iomazenil binding potential measured in vitro in 12 postmortem samples was found to be consistent with SPECT in vivo measurements. Conclusion: These studies demonstrated the feasibility of quantification of receptor binding with SPECT. C1 YALE UNIV, SCH MED, DEPT PSYCHIAT, NEW HAVEN, CT USA. YALE UNIV, SCH MED, DEPT DIAGNOST RADIOL, NEW HAVEN, CT 06510 USA. VET ADM MED CTR, W HAVEN, CT USA. ST ELIZABETH HOSP, NIMH, CTR NEUROSCI, IRP, WASHINGTON, DC 20032 USA. RI Bremner, James/B-1632-2013 NR 53 TC 138 Z9 138 U1 1 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD FEB PY 1994 VL 35 IS 2 BP 228 EP 238 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA MX196 UT WOS:A1994MX19600012 PM 8294990 ER PT J AU MCAFEE, JG AF MCAFEE, JG TI IMAGING VASCULAR ENDOTHELIAL ACTIVATION SO JOURNAL OF NUCLEAR MEDICINE LA English DT Editorial Material RP MCAFEE, JG (reprint author), NIH,DEPT NUCL MED,BLDG 10,ROOM IC401,BETHESDA,MD 20892, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD FEB PY 1994 VL 35 IS 2 BP 281 EP 281 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA MX196 UT WOS:A1994MX19600022 PM 8294999 ER PT J AU MOSS, HA BROUWERS, P WOLTERS, PL WIENER, L HERSH, S PIZZO, PA AF MOSS, HA BROUWERS, P WOLTERS, PL WIENER, L HERSH, S PIZZO, PA TI THE DEVELOPMENT OF A Q-SORT BEHAVIORAL RATING PROCEDURE FOR PEDIATRIC HIV PATIENTS SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Article DE PEDIATRIC AIDS; ENCEPHALOPATHIC; Q-SORT RATING; ABERRANT BEHAVIOR; AZT TREATMENT ID CHILDREN; ENCEPHALITIS; INFECTION; INFUSION; DISEASE; AUTISM AB Developed a Q-sort procedure to assess social, emotional, and motivational behavior associated with central nervous system disease among 180 HIV-infected pediatric patients. These ratings were factor analyzed and scales were derived based on the factor structure. Younger (M age = 1.03 years) patients with HIV-associated encephalopathy were rated as more apathetic and nonsocial in their behavior than nonencephalopathic younger patients. Older (M age = 7.8 years) encephalopathic patients had significantly higher scores on scales measuring depression, autism, and irritability compared to nonencephalopathic patients from this age group. A subgroup (26 patients) showed a significant decrease in these elevated scores after a 6-month course of AZT. C1 MED ILLNESS COUNSELING CTR,CHEVY CHASE,MD. RP MOSS, HA (reprint author), NCI,PEDIAT BRANCH,BETHESDA,MD 20892, USA. FU NCI NIH HHS [NCI-CM-17529-41] NR 29 TC 28 Z9 29 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0146-8693 J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD FEB PY 1994 VL 19 IS 1 BP 27 EP 46 DI 10.1093/jpepsy/19.1.27 PG 20 WC Psychology, Developmental SC Psychology GA MU670 UT WOS:A1994MU67000005 PM 8151493 ER PT J AU WOLTERS, PL BROUWERS, P MOSS, HA PIZZO, PA AF WOLTERS, PL BROUWERS, P MOSS, HA PIZZO, PA TI ADAPTIVE-BEHAVIOR OF CHILDREN WITH SYMPTOMATIC HIV-INFECTION BEFORE AND AFTER ZIDOVUDINE THERAPY SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Article DE PEDIATRIC AIDS; HIV INFECTION; ENCEPHALOPATHY; BEHAVIOR; QUALITY OF LIFE; ZIDOVUDINE; THERAPY ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFUSION AB Assessed longitudinally the effects of HIV infection and zidovudine on the adaptive behavior of 25 children with symptomatic disease (M age = 5.3 years; range = 1-12; 52% classified as encephalopathic) by parent report using the Vineland Adaptive Behavior Scales. Patients also were evaluated with an age-appropriate intelligence test and Q-sort Behavioral Rating Scale. Before treatment, encephalopathic children exhibited greater impairments in adaptive behavior than those without encephalopathy. After 6 months of zidovudine, all behavioral domains (communication, daily living, socialization) except for motor skills showed overall significant improvement. Children with or without encephalopathy showed a similar degree of change. Improvements in adaptive behavior correlated with increases in cognitive ability and decreases in severity of aberrant social-emotional behavior. C1 MED ILLNESS COUNSELING CTR,CHEVY CHASE,MD. RP WOLTERS, PL (reprint author), NCI,PEDIAT BRANCH,BLDG 10,ROOM 13N240,BETHESDA,MD 20892, USA. FU NCI NIH HHS [NCI-CM-1729-41] NR 21 TC 40 Z9 43 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0146-8693 J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD FEB PY 1994 VL 19 IS 1 BP 47 EP 61 DI 10.1093/jpepsy/19.1.47 PG 15 WC Psychology, Developmental SC Psychology GA MU670 UT WOS:A1994MU67000006 PM 8151495 ER PT J AU GERLOCZY, A HOSHINO, T PITHA, J AF GERLOCZY, A HOSHINO, T PITHA, J TI SAFETY OF ORAL CYCLODEXTRINS - EFFECTS OF HYDROXYPROPYL CYCLODEXTRINS, CYCLODEXTRIN SULFATES AND CATIONIC CYCLODEXTRINS ON STEROID BALANCE IN RATS SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID BETA-CYCLODEXTRIN; BILE-SALTS; DISSOLUTION; CARCINOGENS AB Derivatives of beta-cyclodextrin differing in the length of a hydroxyalkyl substituent (CH2CH2OH, CH2CHOHCH3, CH2CHOHCH2CH2CH2CH3) or in the electrical charge of the substituents (SO4-, CH2CHOHCH2N(CH3)(3)(+)) and hydroxypropyl derivatives (CH2CHOHCH3) of alpha-, beta-, and gamma-cyclodextrin were compared, individually and in mixtures, as solubilizers of cholesterol. The most effective solubilizer proved to be hydroxypropyl derivatives of beta-cyclodextrin; beta-cyclodextrin sulfate (SO4-) was practically devoid of solubilizing activity. Oral administration of these cyclodextrin derivatives, some of which are both nondegradable and effective complexation agents for cholesterol and bile acids, nevertheless did not affect the conversion of [C-14] acetic acid to [C-14]- cholesterol in rat under the same conditions when another bile acid complexation agent, cholestyramine, increased that conversion. Thus, complexation of cholesterol and of bile acids by cyclodextrin derivatives, which is a significant and well-defined phenomenon in vitro, seems to have limited importance in terms of excretion of cholesterol from the gastrointestinal tract. It is proposed that various untoward effects observed after chronic large oral doses of hydroxypropyl beta-cyclodextrin are administered are not caused by an increased excretion of some vital lipophile or enzyme but are probably caused by solubilization and increased absorption of toxic contaminants of the ingested food. C1 NIA,GRC,BALTIMORE,MD 21224. RP GERLOCZY, A (reprint author), CYCLOLAB,POB 435,H1525,H-1025 BUDAPEST,HUNGARY. NR 21 TC 24 Z9 25 U1 0 U2 2 PU AMER PHARMACEUTICAL ASSN PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD FEB PY 1994 VL 83 IS 2 BP 193 EP 196 DI 10.1002/jps.2600830215 PG 4 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA MV470 UT WOS:A1994MV47000014 PM 8169787 ER PT J AU TORTELLA, FC ROBLES, L WITKIN, JM NEWMAN, AH AF TORTELLA, FC ROBLES, L WITKIN, JM NEWMAN, AH TI NOVEL ANTICONVULSANT ANALOGS OF DEXTROMETHORPHAN - IMPROVED EFFICACY, POTENCY, DURATION AND SIDE-EFFECT PROFILE SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID METHYL-D-ASPARTATE; GUINEA-PIG BRAIN; PHENCYCLIDINE-LIKE DRUGS; BINDING-SITES; PHARMACOLOGICAL FACTORS; LABORATORY EVALUATION; INDUCED CONVULSIONS; RECEPTOR LIGANDS; RAT-BRAIN; DEXTRORPHAN AB The anticonvulsant and neuroprotective activity of dextromethorphan (DM, [+]-3-methyl-17-methylmorphinan) may be, in part, due to its metabolism to the phencyclidine hydrochloride-like compound dextrorphan (DX). We evaluated the anticonvulsant activity and neurological impairing effects in rats of three novel analogs of DM which, based upon their position-3 substituents, would either not be expected to be metabolized to DX or might do so at a reduced rate. The DM analogs were determined to be more potent and more efficacious than DM against maximal electroshock convulsions; two of the analogs, namely [(+)-3-ethoxy-17- methylmorphinan] and [(+)-3-(2-propoxy)-17-methylmorphinan], were equipotent to DX. [(+)3-Ethoxy-17-methylmorphinan] and L[(+)-3-(2-propoxy)-17-methylmorphinan) exhibited a duration of action (1-2 hr) slightly longer than DX (0.5-1 hr) and similar to DM (2-4 hr). The anticonvulsant effect of [(+)3-amino-17- methylmorphinan] persisted 4-6 hr. Against flurothyl convulsions DM was proconvulsant, DX was anticonvulsant and the DM analogs were inactive. In contrast, N-methyl-D-aspartate convulsions were antagonized by i.c.v. pretreatment with DM and the DM analogs, albeit with a potency approximately 10 times less than that of DX. Results of rotarod performance testing further distinguished the analogs from DM, DX or the anticonvulsant drug diazepam. No behavioral impairment was observed at the highest doses tested of each of the DM analogs, resulting in protective indices (i.e., rotarod TD50/maximal electroshock anticonvulsant ED(50)) greatly exceeding DM, DX or clinical anticonvulsant drugs. The results of this study establish these 3-substituted DM analogs as novel anticonvulsants exhibiting improved potency, efficacy, duration and side-effect profiles. C1 NIDA,ADDICT RES CTR,PSYCHOBIOL SECT,DRUG DEV GRP,BALTIMORE,MD 21224. RP TORTELLA, FC (reprint author), WALTER REED ARMY INST RES,DEPT MED NEUROSCI,NEUROPHARMACOL BRANCH,WASHINGTON,DC 20307, USA. NR 53 TC 29 Z9 29 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD FEB PY 1994 VL 268 IS 2 BP 727 EP 733 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MY586 UT WOS:A1994MY58600028 PM 8113984 ER PT J AU SHAH, AM MEBAZAA, A CUDA, G XIAO, R SELLERS, JR DODD, JM ROBOTHAM, JL LAKATTA, EG AF SHAH, AM MEBAZAA, A CUDA, G XIAO, R SELLERS, JR DODD, JM ROBOTHAM, JL LAKATTA, EG TI CA2+-INDEPENDENT INHIBITION OF ACTOMYOSIN CROSSBRIDGE CYCLING IN CARDIAC MYOCYTES BY ENDOTHELIAL-CELL FACTORS IN RESPONSE TO HYPOXIA SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Meeting Abstract C1 NIH,CARDIOVASC SCI LAB,BALTIMORE,MD. JOHNS HOPKINS UNIV,PULM ANESTHESIA LAB,BALTIMORE,MD. NIH,MOLEC CARDIOL LAB,BETHESDA,MD 20892. UNIV WALES COLL CARDIFF,COLL MED,DEPT CARDIOL,CARDIFF CF4 4XN,S GLAM,WALES. RI Cuda, Giovanni/F-5359-2012 OI Cuda, Giovanni/0000-0001-6313-1866 NR 1 TC 3 Z9 3 U1 1 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD FEB PY 1994 VL 475P BP P80 EP P80 PG 1 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA NA541 UT WOS:A1994NA54100140 ER PT J AU GITTERMAN, M WEISS, GH AF GITTERMAN, M WEISS, GH TI A TRANSITION IN A NOISY LINEAR-SYSTEM DRIVEN BY A PERIODIC SIGNAL SO JOURNAL OF STATISTICAL PHYSICS LA English DT Note DE STOCHASTIC RESONANCE; 1ST PASSAGE TIMES ID ELECTROPHORESIS AB We consider a one-dimension linear random walk between two trapping points in which the transition probabilities vary periodically in time. An earlier analysis of this system showed that the mean time to trapping of a particle in this system exhibits a minimum when considered as a function of frequency. In this note we show that this parameter makes a transition in behavior from a monotonic decrease with increasing amplitude of the periodic term to a monotonic increase with this parameter depending on the frequency. A physical argument is suggested to.explain this behavior. Confirmation of this crossover can also be derived from a diffusion model. C1 BAR ILAN UNIV,DEPT PHYS,IL-52100 RAMAT GAN,ISRAEL. RP GITTERMAN, M (reprint author), NIH,DCRT,PHYS SCI LAB,BETHESDA,MD 20892, USA. NR 8 TC 7 Z9 7 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0022-4715 J9 J STAT PHYS JI J. Stat. Phys. PD FEB PY 1994 VL 74 IS 3-4 BP 941 EP 946 DI 10.1007/BF02188587 PG 6 WC Physics, Mathematical SC Physics GA NA753 UT WOS:A1994NA75300019 ER PT J AU GITTERMAN, M WEISS, GH AF GITTERMAN, M WEISS, GH TI A COMMENT ON EARLY-TIME SOLUTIONS OF THE SMOLUCHOWSKI EQUATION SO JOURNAL OF STATISTICAL PHYSICS LA English DT Note DE EIGENFUNCTION EXPANSIONS; SMOLUCHOWSKI EQUATION AB We present a simple derivation of classes of early-time solutions of the Smoluchowski equation in the presence of boundaries, simplifying and generalizing an analysis by van Kampen. C1 BAR ILAN UNIV,DEPT PHYS,IL-52100 RAMAT GAN,ISRAEL. RP GITTERMAN, M (reprint author), NIH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20892, USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0022-4715 J9 J STAT PHYS JI J. Stat. Phys. PD FEB PY 1994 VL 74 IS 3-4 BP 947 EP 951 DI 10.1007/BF02188588 PG 5 WC Physics, Mathematical SC Physics GA NA753 UT WOS:A1994NA75300020 ER PT J AU ELIA, J GULOTTA, C ROSE, SR MARIN, G RAPOPORT, JL AF ELIA, J GULOTTA, C ROSE, SR MARIN, G RAPOPORT, JL TI THYROID-FUNCTION AND ATTENTION-DEFICIT HYPERACTIVITY DISORDER SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE ADHD; THYROID FUNCTION; HYPERACTIVITY; GENETICS ID TARGET ORGAN RESISTANCE; PERIPHERAL RESISTANCE; HORMONE; DISTURBANCE; THYROTROPIN; PITUITARY AB Objective: To examine thyroid indices in a community referred sample of boys with attention-deficit hyperactivity disorder (ADHD) for evidence of generalized resistance to thyroid hormone (GRTH). Method: TSH, T3, and T4 values were gathered prospectively in 53 physician, school, and/or parent referred ADHD subjects, and in 41 age and gender-matched normal controls. Results: None were in the range suggestive of global or pituitary thyroid hormone resistance. Conclusions: GRTH is rare, and thyroid function should not be measured routinely in nonfamilial ADHD. C1 NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD. MED COLL PENN,DEPT PSYCHIAT,PHILADELPHIA,PA 19129. VIRGINIA POLYTECH INST & STATE UNIV,DEPT PSYCHOL,BLACKSBURG,VA 24061. UNIV TENNESSEE CTR HLTH SCI,DEPT PEDIAT,MEMPHIS,TN 38163. NR 20 TC 48 Z9 48 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD FEB PY 1994 VL 33 IS 2 BP 169 EP 172 DI 10.1097/00004583-199402000-00003 PG 4 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA MT230 UT WOS:A1994MT23000003 PM 8150787 ER PT J AU ROGERS, WJ JOHNSTONE, DE YUSUF, S WEINER, DH GALLAGHER, P BITTNER, VA AHN, S SCHRON, E SHUMAKER, SA SHEFFIELD, LT AF ROGERS, WJ JOHNSTONE, DE YUSUF, S WEINER, DH GALLAGHER, P BITTNER, VA AHN, S SCHRON, E SHUMAKER, SA SHEFFIELD, LT TI QUALITY-OF-LIFE AMONG 5,025 PATIENTS WITH LEFT-VENTRICULAR DYSFUNCTION RANDOMIZED BETWEEN PLACEBO AND ENALAPRIL - THE STUDIES OF LEFT-VENTRICULAR DYSFUNCTION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CONGESTIVE-HEART-FAILURE; OF-LIFE; MYOCARDIAL-INFARCTION; TRIAL; RELIABILITY; MORTALITY; VALIDITY AB Objectives. This study was performed to assess the quality of life of patients with left ventricular dysfunction for up to 2 years after randomization to enalapril or placebo. Background. Previous reports have documented that survival of patients with congestive heart failure can be extended by the angiotensin-converting enzyme inhibitor enalapril. However, it is unknown whether enalapril has a long-term favorable impact on the quality of life in patients with heart failure. Methods. A brief quality of life questionnaire assessing the quality of life was administered at baseline and at 6 weeks, 1 year and 2 years of follow-up to patients randomized to placebo or enalapril in the Studies of Left Ventricular Dysfunction (SOLVD). Participants had an ejection fraction less than or equal to 0.35, no other serious illnesses and either symptomatic heart failure (treatment trial, n = 2,465) or asymptomatic left ventricular dysfunction (prevention trial, n = 2,560). Results. Among the 14 scales of quality of life, better scores at one or more follow-up intervals were noted in 6 scales in the treatment trial and in 1 scale in the prevention trial among patients assigned to enalapril. Consistent superiority with enalapril at two consecutive follow-up intervals was noted in the treatment trial for social functioning and dyspnea but for no scale in the prevention trial. However, an average of 40% of quality of life responses were missing at 2 years of follow-up because of death or failure to complete the questionnaire. In the treatment trial, survivors with more severe heart failure were less likely to complete the questionnaire. Conclusions. Modest benefits in quality of life for greater than or equal to 1 year occurred when patients with left ventricular dysfunction and symptomatic heart failure were treated with enalapril. No apparent beneficial or adverse effect on quality of life was observed with enalapril in asymptomatic patients with left ventricular dysfunction. C1 VICTORIA GEN HOSP,HALIFAX B3H 2Y9,NS,CANADA. MCMASTER UNIV,HAMILTON,ON,CANADA. UNIV N CAROLINA,CHAPEL HILL,NC. UNIV CATHOLIQUE LOUVAIN,B-1200 BRUSSELS,BELGIUM. NIH,BETHESDA,MD 20892. BOWMAN GRAY SCH MED,WINSTON SALEM,NC. RP ROGERS, WJ (reprint author), UNIV ALABAMA,MED CTR,334 LHR BLDG,BIRMINGHAM,AL 35294, USA. NR 29 TC 124 Z9 124 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 VL 23 IS 2 BP 393 EP 400 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA NR752 UT WOS:A1994NR75200019 PM 8294693 ER PT J AU ATTUBATO, MJ SLATER, J FEIT, F BILYK, F MICKEL, M KRONZON, I AF ATTUBATO, MJ SLATER, J FEIT, F BILYK, F MICKEL, M KRONZON, I TI TEMPORARY IMPROVEMENT AFTER BALLOON MITRAL COMMISSUROTOMY - INCIDENCE, DEMOGRAPHICS, AND CLINICAL PREDICTORS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI,NEW YORK,NY. NHLBI,SEATTLE,WA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A61 EP A61 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800237 ER PT J AU CHOI, BW BALLY, M CHOII, BG KATSIYANNIS, P DENNIS, B EMONNOT, B BERTRAND, B CONTARD, M MACHECOURT, J LEWINTER, M AF CHOI, BW BALLY, M CHOII, BG KATSIYANNIS, P DENNIS, B EMONNOT, B BERTRAND, B CONTARD, M MACHECOURT, J LEWINTER, M TI EXERCISE-INDUCED STRUCTURAL REMODELING OF LEFT-VENTRICLE IN SUPER ATHLETES SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 ALBERTVILLE HOSP,ALBERTVILLE,AL. UNIV GRENOBLE 1,F-38041 GRENOBLE,FRANCE. NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A328 EP A328 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801297 ER PT J AU FLEG, JL MAYUGA, R ARRINGTON, CT OCONNOR, F AF FLEG, JL MAYUGA, R ARRINGTON, CT OCONNOR, F TI CLINICAL AND ECHOCARDIOGRAPHIC PREDICTORS OF EXERCISE-INDUCED SUPRAVENTRICULAR ARRHYTHMIAS IN HEALTHY-VOLUNTEERS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NIA,GERONTOL RECH CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A101 EP A101 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800395 ER PT J AU GARCIA, CE KILCOYNE, CM QUYYUMI, AA CANNON, RO PANZA, JA AF GARCIA, CE KILCOYNE, CM QUYYUMI, AA CANNON, RO PANZA, JA TI ROLE OF ENDOTHELIUM-DERIVED NITRIC-OXIDE IN THE VASODILATOR RESPONSE TO BRADYKININ IN NORMOTENSIVE AND HYPERTENSIVE HUMANS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A347 EP A347 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801373 ER PT J AU GARG, R YUSUF, S GORLIN, R AF GARG, R YUSUF, S GORLIN, R TI INCLUSION OF PATIENTS ONLY WITH LOW EJECTION FRACTION IN HEART-FAILURE TRIAL BIASES THE POPULATION AGAINST WOMEN AND THE ELDERLY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI,DIGITALS INVEST GRP,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A429 EP A429 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801699 ER PT J AU GILLIGAN, DM BADAR, DA GUETTA, V QUYYUMI, AA PANZA, JA CANNON, RO AF GILLIGAN, DM BADAR, DA GUETTA, V QUYYUMI, AA PANZA, JA CANNON, RO TI ESTRADIOL POTENTIATION OF ENDOTHELIUM-DEPENDENT VASODILATION IS DEPENDENT ON NITRIC-OXIDE PRODUCTION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A378 EP A378 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801494 ER PT J AU GILLIGAN, DM BADAR, DA QUYYUMI, AA PANZA, JA CANNON, RO AF GILLIGAN, DM BADAR, DA QUYYUMI, AA PANZA, JA CANNON, RO TI DIFFERENTIAL-EFFECTS OF ESTROGEN IN POSTMENOPAUSAL WOMEN WITH PRESENCE OR ABSENCE OF VASCULAR DYSFUNCTION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A377 EP A377 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801493 ER PT J AU KATSIYIANNIS, PT DAKAK, N QUYYUMI, AA ELLIOT, E NERIA, A DILSIZIAN, V AF KATSIYIANNIS, PT DAKAK, N QUYYUMI, AA ELLIOT, E NERIA, A DILSIZIAN, V TI COMPARISON OF SESTAMIBI PERFUSION DEFECTS AND LUNG HEART RATIO DURING EXERCISE WITH KNOWN INDEXES AND ADVERSE PROGNOSIS IN PATIENTS WITH CORONARY-ARTERY DISEASE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A158 EP A158 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800624 ER PT J AU KATSIYIANNIS, PT ARRIGHI, JA QUYYUMI, AA BONOW, RO BACHARACH, SL STUHLMULLER, JE DILSIZIAN, V AF KATSIYIANNIS, PT ARRIGHI, JA QUYYUMI, AA BONOW, RO BACHARACH, SL STUHLMULLER, JE DILSIZIAN, V TI DO PERSISTENT REGIONAL WALL-MOTION ABNORMALITIES AFTER EXERCISE REPRESENT STUNNED MYOCARDIUM SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A79 EP A79 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800310 ER PT J AU KENNY, A SAHN, DJ SHIOTA, T PASSAFINI, A PANTELY, G ARAI, A JONES, M GE, SP YAMADA, I RELLAR, MD AF KENNY, A SAHN, DJ SHIOTA, T PASSAFINI, A PANTELY, G ARAI, A JONES, M GE, SP YAMADA, I RELLAR, MD TI A NEW PHASE-SHIFT ECHO CONTRAST AGENT - ECHOGEN(R) (SONUS-PHARMACEUTICALS) BECOMES A GAS IN BLOOD TO PRODUCE LEFT-HEART AND QUANTIFIABLE MYOCARDIAL CONTRAST AFTER VENOUS INJECTION - STUDIES IN SHEEP AND MONKEYS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 LAMS,NHLBI,BETHESDA,MD. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A450 EP A450 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801783 ER PT J AU KRONZON, I SLATER, J ATTUBATO, MJ FEIT, F MICKEL, M AF KRONZON, I SLATER, J ATTUBATO, MJ FEIT, F MICKEL, M TI ECHOCARDIOGRAPHIC CORRELATES OF ONLY TEMPORARY IMPROVEMENT AFTER MITRAL BALLOON COMMISSUROTOMY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI,BALLOON VALVULOPLASTY REGISTRY,NEW YORK,NY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A194 EP A194 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800763 ER PT J AU LAZAROUS, DF SHOU, M SCHEINOWITZ, M EPSTEIN, SE UNGER, EF AF LAZAROUS, DF SHOU, M SCHEINOWITZ, M EPSTEIN, SE UNGER, EF TI COMPARATIVE EFFECTS OF BASIC FIBROBLAST GROWTH-FACTOR AND VASCULAR ENDOTHELIAL GROWTH-FACTOR ON CORONARY COLLATERAL DEVELOPMENT AND THE ARTERIAL RESPONSE TO INJURY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A177 EP A177 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800697 ER PT J AU MCAREAVEY, D EPSTEIN, ND FANANAPAZIR, L AF MCAREAVEY, D EPSTEIN, ND FANANAPAZIR, L TI DUAL-CHAMBER PACING IS EFFECTIVE THERAPY FOR HYPERTROPHIC CARDIOMYOPATHY PATIENTS WITH PROVOCABLE LV OUTFLOW TRACT OBSTRUCTION AND SYMPTOMS REFRACTORY TO MEDICAL THERAPY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A11 EP A11 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800037 ER PT J AU MCAREAVEY, D FANANAPAZIR, L AF MCAREAVEY, D FANANAPAZIR, L TI ACUTE PACING STUDIES ARE NOT VALUABLE IN PREDICTING LONG-TERM BENEFITS OF DDD PACING FOR LV OUTFLOW OBSTRUCTION N HYPERTROPHIC CARDIOMYOPATHY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A10 EP A10 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800036 ER PT J AU ODONOGHUE, S PLATIA, E MISPIRETA, L BOYCE, S PANZA, J TRIPODI, D MCAREAVEY, D FANANAPAZIR, L AF ODONOGHUE, S PLATIA, E MISPIRETA, L BOYCE, S PANZA, J TRIPODI, D MCAREAVEY, D FANANAPAZIR, L TI SAFETY OF DEFIBRILLATOR IMPLANTATION IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 WASHINGTON HOSP CTR,WASHINGTON,DC 20010. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A11 EP A11 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800038 ER PT J AU PANZA, JA DILSIZIAN, V LAURIENZO, JM KATSIYIANNIS, PT AF PANZA, JA DILSIZIAN, V LAURIENZO, JM KATSIYIANNIS, PT TI MYOCARDIAL CONTRACTILE RESPONSE TO DOBUTAMINE IS RELATED TO THE MAGNITUDE OF THALLIUM UPTAKE IN PATIENTS WITH CORONARY-ARTERY DISEASE AND CHRONIC LEFT-VENTRICULAR DYSFUNCTION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A344 EP A344 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801360 ER PT J AU PANZA, JA GARCIA, CE KILCOYNE, CM QUYYUMI, AA CANNON, RO AF PANZA, JA GARCIA, CE KILCOYNE, CM QUYYUMI, AA CANNON, RO TI IMPAIRED ENDOTHELIUM-DEPENDENT VASODILATION IN PATIENTS WITH ESSENTIAL-HYPERTENSION - EVIDENCE FOR A GENERALIZED ENDOTHELIAL ABNORMALITY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A274 EP A274 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801083 ER PT J AU QUYYUMI, AA DAKAK, N ARORA, S GILLIGAN, DM JOHNSON, GB PANZA, JA ANDREWS, NP CANON, RO AF QUYYUMI, AA DAKAK, N ARORA, S GILLIGAN, DM JOHNSON, GB PANZA, JA ANDREWS, NP CANON, RO TI EFFECT OF INHIBITION OF NITRIC-OXIDE SYNTHESIS IN THE HUMAN CORONARY CIRCULATION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A427 EP A427 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801693 ER PT J AU QUYYUMI, AA DAKAK, N ARORA, S GILLIGAN, DM PANZA, JA ANDREWS, NP CANNON, RO AF QUYYUMI, AA DAKAK, N ARORA, S GILLIGAN, DM PANZA, JA ANDREWS, NP CANNON, RO TI CONTRIBUTION OF NITRIC-OXIDE RELEASE TO METABOLIC VASODILATION IN THE HUMAN HEART SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A274 EP A274 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801084 ER PT J AU RAINA, A BACHARACH, SL JAN, BM LEE, JT GUYYUMI, AA DILSIZIAN, V AF RAINA, A BACHARACH, SL JAN, BM LEE, JT GUYYUMI, AA DILSIZIAN, V TI FUNCTIONAL OUTCOME OF MILD-TO-MODERATE AND SEVERE IRREVERSIBLE THALLIUM DEFECTS AFTER REVASCULARIZATION AS ASSESSED BY MAGNETIC-RESONANCE-IMAGING SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A423 EP A423 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801676 ER PT J AU SACK, MN RADER, DJ CANNON, RO AF SACK, MN RADER, DJ CANNON, RO TI ESTROGEN ADMINISTRATION INHIBITS OXIDATIVE MODIFICATION OF LDL IN POSTMENOPAUSAL WOMEN SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 GEORGETOWN UNIV,WASHINGTON,DC 20007. NHLBI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A481 EP A481 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801909 ER PT J AU SACK, MN RADER, DJ GILLIGAN, DM GUETTA, V CANNON, RO AF SACK, MN RADER, DJ GILLIGAN, DM GUETTA, V CANNON, RO TI EFFECT OF VITAMIN-A, VITAMIN-C, AND VITAMIN-E ON OXIDATIVE MODIFICATION OF LDL FROM HYPERCHOLESTEROLEMIC SUBJECTS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. GEORGETOWN UNIV,WASHINGTON,DC 20057. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A431 EP A431 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801707 ER PT J AU SHANDAS, R JONES, M SHIOTA, T YAMADA, I TEIEN, D SAHN, DJ AF SHANDAS, R JONES, M SHIOTA, T YAMADA, I TEIEN, D SAHN, DJ TI A COMPUTERIZED METHOD FOR CALCULATING CARDIAC-OUTPUT BASED ON REAL-TIME COLOR DOPPLER IMAGES USING THE PROXIMAL FLOW CONVERGENCE TECHNIQUE - EXPERIMENTAL STUDIES IN AN ANIMAL-MODEL SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 OREGON HLTH SCI UNIV,PORTLAND,OR 97201. NHLBI,LAMS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A409 EP A409 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801621 ER PT J AU SHIOTA, T TEIEN, D JONES, M YAMADA, I FRY, P PASSAFINI, A SAHN, DJ AF SHIOTA, T TEIEN, D JONES, M YAMADA, I FRY, P PASSAFINI, A SAHN, DJ TI EVALUATION OF MITRAL REGURGITATION MURMURS USING A NEW DIGITAL HEART-SOUND RECORDING METHOD WITH REAL-TIME SPECTRAL-ANALYSIS - STUDIES IN AN ANIMAL-MODEL WITH QUANTIFIABLE MITRAL REGURGITATION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI,LAMS,BETHESDA,MD 20892. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A292 EP A292 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801153 ER PT J AU TAMURA, K JONES, M YAMADA, I FERRANS, VJ AF TAMURA, K JONES, M YAMADA, I FERRANS, VJ TI A COMPARISON OF FAILURE MODES OF GLUTARALDEHYDE-TREATED VERSUS ANTIBIOTIC-PRESERVED MITRAL-VALVE ALLOGRAFTS IMPLANTED IN SHEEP SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A248 EP A248 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800979 ER PT J AU TAMURA, K FUKUDA, Y YAMANAKA, N FERRANS, VJ AF TAMURA, K FUKUDA, Y YAMANAKA, N FERRANS, VJ TI STRUCTURAL ABNORMALITIES OF CONNECTIVE-TISSUE IN FLOPPY MITRAL-VALVE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NIPPON MED COLL,TOKYO 113,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A32 EP A32 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800122 ER PT J AU ATIGA, WL MCAREAVEY, D EPSTEIN, ND FANANAPAZIR, L AF ATIGA, WL MCAREAVEY, D EPSTEIN, ND FANANAPAZIR, L TI RISK STRATIFICATION OF ASYMPTOMATIC PATIENTS WITH HYPERTROPIC CARDIOMYOPATHY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP M110 EP M110 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800430 ER PT J AU MARON, BJ SCHIFFERS, A KLUES, HG AF MARON, BJ SCHIFFERS, A KLUES, HG TI MORPHOLOGIC EXPRESSION OF HYPERTROPHIC CARDIOMYOPATHY DIFFERS IN NORTH-AMERICAN AND EUROPEAN PATIENTS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 UNIV HOSP,RWTH,AACHEN,GERMANY. MINNEAPOLIS HEART INST FDN,MINNEAPOLIS,MN. NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP M110 EP M110 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800433 ER PT J AU SHIRANI, J PICK, R SILVER, MA ROBERTS, WC MARON, BJ AF SHIRANI, J PICK, R SILVER, MA ROBERTS, WC MARON, BJ TI IMPORTANCE OF THE COLLAGEN MATRIX IN YOUNG-PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY AND SUDDEN-DEATH SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP M110 EP M110 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800431 ER PT J AU COOGAN, TP BARE, RM BJORNSON, EJ WAALKES, MP AF COOGAN, TP BARE, RM BJORNSON, EJ WAALKES, MP TI ENHANCED METALLOTHIONEIN GENE-EXPRESSION IS ASSOCIATED WITH PROTECTION FROM CADMIUM-INDUCED GENOTOXICITY IN CULTURED RAT-LIVER CELLS SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH LA English DT Article ID CHINESE-HAMSTER CELLS; CYTO-TOXICITY; IMMUNOHISTOCHEMICAL LOCALIZATION; MAMMALIAN-CELLS; DNA; INDUCTION; PRETREATMENT; INHIBITION; ZINC; LYMPHOCYTES AB Metallothioneins (MTs) are low-molecular-weight, cysteine-rich proteins that appear to play an important role in the cellular defense system against cadmium toxicity. Although substantial evidence exists demonstrating a reduction in cadmium toxicity concomitant with MT induction, little is known about the possible effects of stimulation of MT synthesis on cadmium-induced genotoxicity. Thus, the alkaline elution technique was used to assess single-strand DNA damage (SSD) in TRL-1215 cells, a liver-derived cell line shown to have inducible MT gene expression. The SSD accumulated over a 2-h time period in a time-dependent manner following exposure to 500 mu M CdCl2. low-concentration cadmium pretreatment (10 mu M CdCl2, 24 h) provided protection against the genotoxicity of high-concentration cadmium (500 mu M CdCl2, 2 h). A 2-h exposure to 500 mu M CdCl2 had no effect on viability, as assessed using a tetrazolium-dye based assay, in cells from either the pretreated or nonpretreated group. Metallothionein was induced in a time-dependent manner by low-concentration cadmium pretreatment: Exposure for 24 and 48 h resulted in 3.3- and 6.4-fold increases, respectively. In addition, a 24-h exposure to low-concentration cadmium resulted in an increase in MT-I gene expression. Cadmium accumulation was 2.6-fold greater in low-concentration cadmium-pretreated cells as compared to nonpretreated cells. These data demonstrate that low-concentration cadmium pretreatment provides protection against cadmium-induced single-strand PNA damage and support the hypothesis that this protection is due to stimulation of MT gene expression. C1 NCI,FCRDC,COMPARAT CARCINOGENESIS LAB,INORGAN CARCINOGENESIS SECT,FREDERICK,MD 21702. NR 38 TC 51 Z9 52 U1 0 U2 0 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 FEB PY 1994 VL 41 IS 2 BP 233 EP 245 PG 13 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA MV874 UT WOS:A1994MV87400006 PM 8301701 ER PT J AU SIEGSMUND, MJ CARDARELLI, C AKSENTIJEVICH, I SUGIMOTO, Y PASTAN, I GOTTESMAN, MM AF SIEGSMUND, MJ CARDARELLI, C AKSENTIJEVICH, I SUGIMOTO, Y PASTAN, I GOTTESMAN, MM TI KETOCONAZOLE EFFECTIVELY REVERSES MULTIDRUG-RESISTANCE IN HIGHLY RESISTANT KB CELLS SO JOURNAL OF UROLOGY LA English DT Article DE DRUG RESISTANCE; GLYCOPROTEINS; PROSTATIC NEOPLASMS; TUMOR STEM CELL ASSAY; KETOCONAZOLE ID P-GLYCOPROTEIN; VINCRISTINE RESISTANCE; PROSTATIC-CANCER; CYTO-TOXICITY; HUMAN-TUMORS; GENE; EXPRESSION; THERAPY; LINES; ACCUMULATION AB The antifungal agent ketoconazole was found to overcome resistance to vinblastine and doxorubicin in multidrug resistant KB-V1 cells in vitro. These cells are several hundred-fold more resistant than the parental cell line KB-3-1. Ketoconazole had little or no effect on the parental KB-3-1 cells. The concentrations used to overcome drug resistance in vitro have already been safely used in vivo for treatment of fungal infections and in the monotherapy of hormone independent prostate carcinomas to block adrenal androgen production. Because of a possible beneficial effect of a combination of ketoconazole and a chemotherapeutic drug in multidrug resistant cancers, we examined a panel of 11 prostate carcinoma tissues for the expression of the MDR1 gene by an RNA-PCR assay. MDR1 expression was detectable, albeit at low levels, in 8 of the 11 tumors, suggesting a possible role of this gene in the drug resistance of prostate carcinomas. Our data suggest that ketoconazole might be useful in overcoming multidrug resistance in concentrations that are achievable in humans. C1 NCI,DCBDC,CELL BIOL LAB,BETHESDA,MD 20892. NCI,DCBDC,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 34 TC 76 Z9 77 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD FEB PY 1994 VL 151 IS 2 BP 485 EP 491 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA MR274 UT WOS:A1994MR27400063 PM 7904313 ER PT J AU EIDEN, MV FARRELL, K WILSON, CA AF EIDEN, MV FARRELL, K WILSON, CA TI GLYCOSYLATION-DEPENDENT INACTIVATION OF THE ECOTROPIC MURINE LEUKEMIA-VIRUS RECEPTOR SO JOURNAL OF VIROLOGY LA English DT Article ID RETROVIRUS RECEPTOR; GENE-TRANSFER; INFECTION; DNA AB The ecotropic murine leukemia virus (E-MuLV) receptor expressed on Mus dunni tail fibroblast (MDTF) cells is a receptor for all E-MuLVs with the notable exception of Moloney murine leukemia virus (Mo-MuLV). Substitution of isoleucine for valine at position 214 in the third extracellular region (the putative E-MuLV binding site) of the MDTF receptor molecule allows this molecule to function as a Mo-MuLV receptor (M. V. Eiden, K. Farrell, J. Warsowe, L.A. Mahan, and C.A. Wilson, J. Virol. 67:4056-4061, 1993). We have now determined that treating MDTF cells with tunicamycin, an inhibitor of N-linked glycosylation, also renders them susceptible to Mo-MuLV infection. Two potential N-linked glycosylation sites are present in the third extracellular regions of both the NIH 3T3 and MDTF ecotropic receptors. The glycosylation site at position 229 of the MDTF receptor cDNA was eliminated by substituting a threonine codon for the asparagine codon. Mo-MuLV-resistant human HOS cells, expressing this form of the receptor, are susceptible to Mo-MuLV infection. Thus, our studies suggest that without a glycan moiety at position 229, the valine residue at 214 is no longer restrictive for Mo-MuLV infection. BHK-21 and CHO K1 hamster cells also express glycosylation-inactivated forms of the ecotropic receptor. Sequence analysis of these receptors together with our analysis of MDTF receptor function suggests that a single asparagine-linked glycosylation site is responsible for glycosylation inactivation of these receptors. RP EIDEN, MV (reprint author), NIMH,CELL BIOL LAB,BLDG 36,ROOM 2D10,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 16 TC 53 Z9 53 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1994 VL 68 IS 2 BP 626 EP 631 PG 6 WC Virology SC Virology GA MW252 UT WOS:A1994MW25200006 PM 8289366 ER PT J AU NAGY, K YOUNG, M BABOONIAN, C MERSON, J WHITTLE, P OROSZLAN, S AF NAGY, K YOUNG, M BABOONIAN, C MERSON, J WHITTLE, P OROSZLAN, S TI ANTIVIRAL ACTIVITY OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 PROTEASE INHIBITORS IN A SINGLE-CYCLE OF INFECTION - EVIDENCE FOR A ROLE OF PROTEASE IN THE EARLY PHASE SO JOURNAL OF VIROLOGY LA English DT Article ID CELL LEUKEMIA-VIRUS; HIV-1 PROTEASE; GENE-EXPRESSION; T-CELLS; DNA; COMPLEX; ENTRY; LINE; RETROVIRUSES; INTEGRATION AB The antiviral activities of two substrate-based inhibitors of human immunodeficiency virus type 1 (HIV-1) protease, UK-88,947 and Ro 31-8959, were studied in acute infections. H9 and HeLaCDC-4LTR/beta-gal cells were infected either with HTV-1(IIIB) or a replication-defective virus, HIV-gpt(HXB-2). Both inhibitors were capable of blocking early steps of HIV-1 replication if added to cells prior to infection. Partial inhibition was also obtained by addition of inhibitor at the time of or as late as 15 min after infection. The inhibitors were ineffective if added 30 min postinfection. The inhibitory effects were studied by cDNA analysis,vith PCR followed by Southern blot hybridization and by infectivity assays allowing quantitation of HIV-1 in a single cycle of replication. When UK-88,947-treated H9 cells were coinfected with HIV-1 and human T-cell leukemia virus type I only the replication of HIV-I was inhibited, demonstrating viral specificity. Pretreating the infectious virus stocks with the inhibitors also prevented replication, indicating that the inhibitors block the action of the viral protease and not a cellular protease. A panel of primer sets aas used to analyze cDNA from cell lysates by PCR amplification at 4 and 18 h postinfection. Four hours after infection, viral specific cDNA was detected with all of the four primer pairs used: R/U5, nef/U3, 5' gag, and long terminal repeat (LTR)/gag. However, after 18 h, only the R/U5 and nef/U3 primer pairs and not the 5' gag or LTR/gag primer pair were able to allow amplification of cDNA. The results suggest a crucial role of HN-I protease in the early phase of viral replication. Although it is not clear what early steps are affected by the protease, it is likely that the target is the NC protein, as referred from our previous reports of the in situ cleavage of the nucleocapsid (NC) protein by the viral protease inside lentiviral capsids. The results suggest that it is not the inhibition of initiation and progression of reverse transcription but the stability of full-size unintegrated cDNA which is affected in the presence of protease inhibitors. Alternatively, the cleavage of the NC protein may be required for the proper formation of preintegration complex and/or for its transport to the nucleus. C1 NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. UNIV N LONDON, LONDON N7 8DB, ENGLAND. PFIZER LTD, CENT RES, SANDWICH CT13 9NJ, KENT, ENGLAND. NR 53 TC 60 Z9 62 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 FEB PY 1994 VL 68 IS 2 BP 757 EP 765 PG 9 WC Virology SC Virology GA MW252 UT WOS:A1994MW25200023 PM 8289379 ER PT J AU CHIORINI, JA WEITZMAN, MD OWENS, RA URCELAY, E SAFER, B KOTIN, RM AF CHIORINI, JA WEITZMAN, MD OWENS, RA URCELAY, E SAFER, B KOTIN, RM TI BIOLOGICALLY-ACTIVE REP PROTEINS OF ADENOASSOCIATED VIRUS TYPE-2 PRODUCED AS FUSION PROTEINS IN ESCHERICHIA-COLI SO JOURNAL OF VIROLOGY LA English DT Article ID INHIBITS CELLULAR-TRANSFORMATION; DOMINANT-NEGATIVE MUTANT; ADENOASSOCIATED VIRUS; GEL-ELECTROPHORESIS; RECOMBINANT PLASMID; VIRAL REPLICATION; HUMAN-CELLS; WILD-TYPE; DNA; GENOME AB Four Rep proteins are encoded by the human parvovirus adeno-associated virus type 2 (AAV). The two largest proteins, Rep68 and Rep78, have been shown in vitro to perform several activities related to AAV DNA replication. The Rep78 and Rep68 proteins are likely to be involved in the targeted integration of the AAV DNA into human chromosome 19, and the full characterization of these proteins is important for exploiting this phenomenon for the use of AAV as a vector for gene therapy. To obtain sufficient quantities for facilitating the characterization of the biochemical properties of the Rep proteins, the AAV rep open reading frame was cloned and expressed in Escherichia coli as a fusion protein with maltose-binding protein (MBP). Recombinant MBP-Rep68 and MBP-Rep78 proteins displayed the following activities reported for wild-type Rep proteins when assayed in vitro: (i) binding to the AAV inverted terminal repeat (ITR), (ii) helicase activity, (iii) site-specific (terminal resolution site) endonuclease activity, (iv) binding to a sequence within the integration locus for AAV DNA on human chromosome 19, and (v) stimulation of radiolabeling of DNA containing the AAV ITR in a cell extract. These five activities have been described for wild-type Rep produced from mammalian cell extracts. Furthermore, we recharacterized the sequence requirements for Rep binding to the ITR and found that only the A and A' regions are necessary, not the hairpin form of the ITR. C1 NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892. NIDDKD,MOLEC & CELLULAR BIOL LAB,BETHESDA,MD 20892. GENET THERAPY INC,GAITHERSBURG,MD 20878. RI kotin, robert/B-8954-2008 NR 35 TC 89 Z9 90 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1994 VL 68 IS 2 BP 797 EP 804 PG 8 WC Virology SC Virology GA MW252 UT WOS:A1994MW25200027 PM 8289383 ER PT J AU SETH, P ROSENFELD, M HIGGINBOTHAM, J CRYSTAL, RG AF SETH, P ROSENFELD, M HIGGINBOTHAM, J CRYSTAL, RG TI MECHANISM OF ENHANCEMENT OF DNA EXPRESSION CONSEQUENT TO COINTERNALIZATION OF A REPLICATION-DEFICIENT ADENOVIRUS AND UNMODIFIED PLASMID DNA SO JOURNAL OF VIROLOGY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; CELL-MEMBRANE PERMEABILITY; KB-CELLS; GENE; PH; BINDING; INFECTION; PARTICLES; DELIVERY; PROTEINS AB Given the knowledge that replication-deficient adenoviruses can mediate the delivery of unlinked plasmid DNA into eukaryotic cells (K. Yoshimura, M. A. Rosenfeld, P. Seth, and R. G. Crystal, J. Biol. Chem. 268:2300-2303, 1993), this study focuses on the role of receptor-mediated endocytosis in this process. AdCFTR (an E1(-) E3(-) adenovirus type 5-based replication-deficient adenovirus containing the 4.5-kb human cystic fibrosis transmembrane conductance regulator cDNA) was added to Cos-7 cells together with plasmid pRSVL (containing the Rous sarcoma virus long terminal repeat promoter followed by the luciferase cDNA), and luciferase activity was quantified as a measure of the expression of the plasmid DNA. When AdCFTR was bound to Cos-7 cells at 4 degrees C and the cells were subsequently incubated at 37 degrees C in tine presence of pRSVL, the expression of luciferase activity was increased in proportion to the amount of AdCFTR added, reaching > 10(4)-fold at 3,000 PFU per cell. AdCFTR-mediated increase in pRSVL was inhibited by addition of purified adenovirus fiber but not hexon, suggesting cell surface adenovirus receptors were involved in the cointernalization process. Cell lines with a high number of adenovirus receptors (Cos-7 and HeLa) showed significant AdCFTR-dependent pRSVL expression, while cell lines with low numbers of adenovirus receptors (NIH 3T3 and U-937) showed little. AdCFTR-mediated increase in the expression of pRSVL was prevented when AdCFTR was heat treated and exposed to antibody against adenovirus or when the cointernalization process was evaluated in the presence of chloroquine, conditions all known to prevent adenovirus-mediated disruption of endocytic vesicles. In contrast, the uptake of AdCFTR into Cos-7 cells was not affected by any of these conditions. When AdCFTR was exposed to UV light, its ability to grow in 293 cells was obviated, but AdCFTR-dependent increase in pRSVL expression was minimally reduced. Finally, empty capsids of AdCFTR were able to enhance the delivery and expression of plasmid pRSVL into Cos-7 cells, suggesting that the adenovirus genome is not required for AdCFTR-mediated plasmid cointernalization. Together, these observations suggest that the ability of a replication-deficient recombinant adenovirus to mediate the cointernalization and expression of plasmids is mediated by the receptor-mediated endocytosis pathway. C1 CORNELL UNIV,COLL MED,DIV PULM & CRIT CARE MED,NEW YORK,NY 10021. RP SETH, P (reprint author), NHLBI,PULM BRANCH,BLDG 10,ROOM 6D03,BETHESDA,MD 20892, USA. NR 29 TC 62 Z9 63 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1994 VL 68 IS 2 BP 933 EP 940 PG 8 WC Virology SC Virology GA MW252 UT WOS:A1994MW25200042 PM 7507187 ER PT J AU MICHAEL, NL VAHEY, MT DARCY, L EHRENBERG, PK MOSCA, JD RAPPAPORT, J REDFIELD, RR AF MICHAEL, NL VAHEY, MT DARCY, L EHRENBERG, PK MOSCA, JD RAPPAPORT, J REDFIELD, RR TI NEGATIVE-STRAND RNA TRANSCRIPTS ARE PRODUCED IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE 1-INFECTED CELLS AND PATIENTS BY A NOVEL PROMOTER DOWN-REGULATED BY TAT SO JOURNAL OF VIROLOGY LA English DT Article ID MOUSE MITOCHONDRIAL-DNA; LONG TERMINAL REPEAT; HTLV-III; PRECISE ASSIGNMENT; REGULATORY ELEMENT; PLUS STRAND; T-CELLS; EXPRESSION; HIV-1; SEQUENCE AB Current understanding of human immunodeficiency virus type 1 (HIV-I) transcription is based on unidirectional expression of transcripts with positive-strand polarity from the 5' long terminal repeat. We now report HIV-1 transcripts' with negative-strand polarity obtained from acutely and chronically infected cell lines by use of a template orientation-specific reverse transcriptase-PCR assay. These findings were confirmed in natural infection by analysis of RNA derived from peripheral blood mononuclear cell samples from 15 HIV-l-infected patients. A cDNA derived from a 2.3-kb polyadenylated HIV-I RNA with negative-strand polarity which encodes a highly conserved 189-amino-acid open reading frame antiparallel to the envelope gene was isolated from acutely infected A3.01 cells. Through use of reporter gene constructions, we further found that a novel negative-strand promoter functions within the negative response element of the 3' long terminal repeat, which is downregulated by coexpression of Tat. Site-directed mutagenesis experiments demonstrated that NF-kappa B I and USF sites are crucial for negative-strand promoter activity. These data extend the coding capacity of HIV-1 and suggest a cole for antisense regulation of the viral life cycle, C1 WALTER REED ARMY INST RES,DEPT RETROVIRAL RES,ROCKVILLE,MD 20850. HENRY M JACKSON FDN,ROCKVILLE,MD 20850. NIDR,ORAL MED LAB,BETHESDA,MD 20892. NR 41 TC 51 Z9 52 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1994 VL 68 IS 2 BP 979 EP 987 PG 9 WC Virology SC Virology GA MW252 UT WOS:A1994MW25200047 PM 8289399 ER PT J AU WILLEY, RL MARTIN, MA PEDEN, KWC AF WILLEY, RL MARTIN, MA PEDEN, KWC TI INCREASE IN SOLUBLE CD4 BINDING TO AND CD4-INDUCED DISSOCIATION OF GP120 FROM VIRIONS CORRELATES WITH INFECTIVITY OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-SEROPOSITIVE INDIVIDUALS; AMINO-ACID CHANGES; ENVELOPE GLYCOPROTEIN; MEMBRANE-FUSION; HOST-RANGE; MACROPHAGE TROPISM; CELL TROPISM; T-CELL; ENDOPROTEOLYTIC CLEAVAGE; TRANSMEMBRANE PROTEIN AB Mutations in the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins gp120 and gp41, previously shown to confer an enhanced replicative capacity and broadened host range to the ELI1 strain of HTV-1, were analyzed for their biochemical effects on envelope structure and function. The tendency of purified virions to release their extracellular gp120 component, either spontaneously or after interacting with soluble CD4 ((CD4-induced shedding) was assessed. A single amino acid substitution in part of the CD4 binding site of gp120 (Gly-427 to Arg) enhanced both spontaneous and CD4-induced shedding of gp120 from virions, while a single change in the fusogenic region of gp41 (Met-7 to Val) affected only CD4-induced shedding. Although each codon change alone conferred increased growth ability, virus with both mutations exhibited the most rapid replication kinetics. In addition, when both of these mutations were present, virions had the highest tendency to shed gp120, both spontaneously and after exposure to soluble CD4. Analysis of CD4 binding to virion-associated gp120 showed that the changes in both gp120 and gp41 contributed to increased binding. These results demonstrated that the increased replicative capacity of the ELI variants in human CD4(+) cell lines was associated with altered physical and functional properties of the virion envelope glycoproteins. C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NR 75 TC 71 Z9 71 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1994 VL 68 IS 2 BP 1029 EP 1039 PG 11 WC Virology SC Virology GA MW252 UT WOS:A1994MW25200052 PM 7904656 ER PT J AU SODEIK, B GRIFFITHS, G ERICSSON, M MOSS, B DOMS, RW AF SODEIK, B GRIFFITHS, G ERICSSON, M MOSS, B DOMS, RW TI ASSEMBLY OF VACCINIA VIRUS - EFFECTS OF RIFAMPIN ON THE INTRACELLULAR-DISTRIBUTION OF VIRAL PROTEIN P65 SO JOURNAL OF VIROLOGY LA English DT Article ID PROTEOLYTIC MATURATION; CORE PROTEINS; GENE; MORPHOGENESIS; POLYPEPTIDE; RESISTANCE; PRECURSORS; BIOGENESIS; MEMBRANES; CLEAVAGE AB The cytoplasmic assembly of vaccinia virus is reversibly blocked by the antibiotic rifampin, leading to the accumulation of partially membrane-delineated rifampin bodies in infected cells. Rifampin-resistant vaccinia virus mutants have point mutations in the D13L gene, which is controlled by a late promoter and expresses a 65-kDa protein, designated p65. To further characterize the mechanism of rifampin inhibition and the function of p65 in virus assembly, we raised antibodies to this protein. Immunoreactive p65 was expressed at late times of infection, and neither its expression nor its turnover was affected by rifampin. Virus-associated p65 could be extracted only with denaturing detergents from purified virions, suggesting that it is an integral viral component. Immunofluorescence studies showed that p65 is localized to the sites of virus assembly. Also, immunoelectron microscopy showed p65 to be associated with viral crescents as well as spherical, immature virions, in both cases predominantly on the inner or concave surface. In the presence of rifampin, p65 was found in large, cytoplasmic inclusion bodies that were distinct from rifampin bodies. The rifampin bodies themselves were labeled with p65 antibodies only after reversal of the rifampin block, predominantly on the viral crescents which rapidly formed following removal of the drug. We propose that p65 functions as an internal scaffold in the formation of viral crescents and immature virions, analogously to the matrix proteins of other viruses. C1 UNIV PENN,SCH MED,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. EUROPEAN MOLEC BIOL LAB,CELL BIOL PROGRAM,D-69012 HEIDELBERG,GERMANY. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. RI Sodeik, Beate/C-9732-2010 NR 37 TC 89 Z9 89 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1994 VL 68 IS 2 BP 1103 EP 1114 PG 12 WC Virology SC Virology GA MW252 UT WOS:A1994MW25200060 PM 8289340 ER PT J AU CHEN, YMA JANG, YJ KANKI, PJ YU, QC WANG, JJ MONTALI, RJ SAMUEL, KP PAPAS, TS AF CHEN, YMA JANG, YJ KANKI, PJ YU, QC WANG, JJ MONTALI, RJ SAMUEL, KP PAPAS, TS TI ISOLATION AND CHARACTERIZATION OF SIMIAN T-CELL LEUKEMIA-VIRUS TYPE-II FROM NEW-WORLD MONKEYS SO JOURNAL OF VIROLOGY LA English DT Article ID NON-HUMAN PRIMATES; COMPLETE NUCLEOTIDE-SEQUENCE; LYMPHOTROPIC VIRUS; HTLV-II; JAPANESE MONKEYS; LYMPHOMA VIRUS; C RETROVIRUS; ANTIGEN ATLA; ANTIBODIES; INFECTION AB Since the description of human T-cell leukemia virus type I (HTLV-I) and its simian counterpart, simian T-cell leukemia virus type I (STLV-I), the possible existence of other related simian retroviruses has been raised. Here, we report a new retrovirus, STLV-II, which we have identified in spider monkeys (Ateles fusciceps), a New World primate species. Initially, a recombinant HTLV-II envelope protein (RP-IIB) was used to identify anti-STLV-II antibodies in New World monkeys by Western blot (immunoblot) assays. Subsequently, the virus was characterized by Southern blot hybridization, which showed that STLV-II and HTLV-II have a high degree of nucleotide sequence homology but have different restriction enzyme patterns. Nucleotide sequence analysis of the pX-II region of STLV-II provirus revealed 3% variation with the corresponding region of HTLV-II. Electron micrographic studies revealed HTLV-like, type C retrovirus particles outside the cell membranes of STLV-II-infected cells. This study describes the first link between HTLV-II and a simian reservoir in the New World. Further molecular studies of STLV-II infection in different species of New World monkeys, especially from the wild, may provide valuable information about the origin and intragroup relationships of South American monkeys. Spider monkeys infected with STLV-II may serve as an important animal model for HTLV-II infection in humans. C1 NATL YANG MING MED COLL,GRAD INST PUBL HLTH,AIDS RES CTR,TAIPEI 11221,TAIWAN. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. UNIV CHICAGO,DEPT MOLEC GENET & CELL BIOL,CHICAGO,IL 60637. SMITHSONIAN INST,NATL ZOOL PK,DEPT PATHOL,WASHINGTON,DC 20008. DYN CORP,PROGRAM RESOURCES INC,BIOTECHNOL WORKING GRP,CELLULAR BIOCHEM LAB,FREDERICK,MD 21701. NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702. RP CHEN, YMA (reprint author), ACAD SINICA,INST BIOMED SCI,TAIPEI 11529,TAIWAN. NR 60 TC 35 Z9 35 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1994 VL 68 IS 2 BP 1149 EP 1157 PG 9 WC Virology SC Virology GA MW252 UT WOS:A1994MW25200064 PM 7507178 ER PT J AU CHEN, M POPESCU, N WOODWORTH, C BERNEMAN, Z CORBELLINO, M LUSSO, P ABLASHI, DV DIPAOLO, JA AF CHEN, M POPESCU, N WOODWORTH, C BERNEMAN, Z CORBELLINO, M LUSSO, P ABLASHI, DV DIPAOLO, JA TI HUMAN HERPESVIRUS-6 INFECTS CERVICAL EPITHELIAL-CELLS AND TRANSACTIVATES HUMAN PAPILLOMAVIRUS GENE-EXPRESSION SO JOURNAL OF VIROLOGY LA English DT Note ID HUMAN-IMMUNODEFICIENCY-VIRUS; MAMMALIAN-CELLS; UTERINE CERVIX; LYMPHOCYTES-T; IDENTIFICATION; DNA; SEQUENCES; TYPE-16; NEOPLASIA; CANCER AB To examine whether human herpesvirus 6 (HHV-6) is capable of infecting human cervical epithelial cells and altering expression of human papillomavirus (HPV) genes, HPV-immortalized or -transformed carcinoma cell lines were infected with HHV-6 variant A. No cytopathic effect was observed in infected cervical cells. However, immunofluorescence indicated that infected cells expressed early-late proteins of HHV-6 by day 3 postinfection. HHV-6 DNA was also detected by Southern blot hybridization after infection and persisted through continued subculture in an episomal state as proven by Gardella gel electrophoresis and fluorescence in situ hybridization. HHV-6 infection enhanced expression of HPV RNAs encoding the viral oncoproteins E6 and E7. Transient transfection assays showed that two HHV-6 molecular clones, pZVB-70 and pZVH-14, upregulated transcription 9- to 15-fold from a reporter plasmid containing the HPV type IS regulatory sequences which control transcription in vivo. Cervical carcinoma cells infected with HHV-6 induced more rapid development of tumors in mice than did noninfected cells. These results are the first evidence that human cervical epithelial cells can be infected with HHV-6 and that HHV-6 contains transactivators which stimulate the HPV-transforming genes. C1 NCI, BIOL LAB, BETHESDA, MD 20892 USA. NCI, TUMOR CELL BIOL LAB, BETHESDA, MD 20892 USA. NCI, CELLULAR & MOLEC BIOL LAB, BETHESDA, MD 20892 USA. NR 46 TC 70 Z9 75 U1 1 U2 2 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 FEB PY 1994 VL 68 IS 2 BP 1173 EP 1178 PG 6 WC Virology SC Virology GA MW252 UT WOS:A1994MW25200067 PM 8289346 ER PT J AU SETH, P AF SETH, P TI ADENOVIRUS-DEPENDENT RELEASE OF CHOLINE FROM PLASMA-MEMBRANE VESICLES AT AN ACIDIC PH IS MEDIATED BY THE PENTON BASE PROTEIN SO JOURNAL OF VIROLOGY LA English DT Note ID EPIDERMAL GROWTH-FACTOR; KB-CELLS; ENHANCEMENT; TOXICITY; PERMEABILITY; BINDING AB It has been suggested that during receptor-mediated endocytosis of human adenovirus (Ad) type 2 into cells, Ad disrupts the membrane of endocytic vesicles to enter the cytosol. To understand the mechanism of Ad-mediated disruption of the endocytic vesicles, I exposed Ad to plasma membrane vesicles derived from KB cells. Ad caused release of choline from the plasma membrane vesicles preloaded dth [H-3]choline. The efflux of choline was dependent on (i) the concentration of Ad, with a half-maximal effect at 0.5 mu g/ml; (ii) the pH of the buffer, with the optimum pH of the reaction ranging from 5.5 to 6.0; (iii) the length of the incubation, with a half-maximal release at 2 min; and (iv) the temperature of the incubation, with the optimum temperature being 37 degrees C. The Ad-dependent release of choline was inhibited by anti-penton base, while antihexon did not block the effect. These results suggest roles for a low-pH environment and the penton base protein in the Ad-dependent efflux of choline from plasma membrane vesicles. C1 NCI,DIV CANC BIOL & DIAG,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 20 TC 75 Z9 75 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1994 VL 68 IS 2 BP 1204 EP 1206 PG 3 WC Virology SC Virology GA MW252 UT WOS:A1994MW25200073 PM 8289352 ER PT J AU WILLEY, RL BUCKLERWHITE, A STREBEL, K AF WILLEY, RL BUCKLERWHITE, A STREBEL, K TI SEQUENCES PRESENT IN THE CYTOPLASMIC DOMAIN OF CD4 ARE NECESSARY AND SUFFICIENT TO CONFER SENSITIVITY TO THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 VPU PROTEIN SO JOURNAL OF VIROLOGY LA English DT Note ID ENDOPLASMIC-RETICULUM; TRANSMEMBRANE PROTEINS; HIV-1; MATURATION; DEGRADATION; TRANSPORT; RETENTION; SIGNALS; GP160; CELLS AB CD4 is an integral membrane glycoprotein which functions as the human immunodeficiency virus receptor for infection of human host cells. We have recently demonstrated that Vpu, a human immunodeficiency virus type 1-encoded integral membrane phosphoprotein, induces rapid degradation of CD4 in the endoplasmic reticulum. Using an in vitro model system, we demonstrated that Vpu targets specific sequences in the cytoplasmic domain of CD4 to promote its degradation. In this report, we have further delineated regions within CD4 which are required for susceptibility to Vpu. Transfer of the CD4 cytoplasmic region into a heterologous protein, CDS, rendered the chimeric protein sensitive to Vpu-dependent degradation. In contrast, substitution of the CD8 transmembrane domain with the analogous region from CD4 did not confer sensitivity to Vpu. Finally, mutant forms of the CD4 protein containing the extracellular region alone or the extracellular and transmembrane regions linked to a heterologous cytoplasmic domain were not targeted by Vpu. Thus, sequences present in the cytoplasmic domain of CD4 are necessary and sufficient to confer sensitivity to Vpu. C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. GEORGETOWN UNIV,DIV MOLEC VIROL & IMMUNOL,ROCKVILLE,MD 20852. NR 25 TC 46 Z9 46 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1994 VL 68 IS 2 BP 1207 EP 1212 PG 6 WC Virology SC Virology GA MW252 UT WOS:A1994MW25200074 PM 8289353 ER PT J AU AUSTIN, HA BOUMPAS, DT VAUGHAN, EM BALOW, JE AF AUSTIN, HA BOUMPAS, DT VAUGHAN, EM BALOW, JE TI PREDICTING RENAL OUTCOMES IN SEVERE LUPUS NEPHRITIS - CONTRIBUTIONS OF CLINICAL AND HISTOLOGIC DATA SO KIDNEY INTERNATIONAL LA English DT Article ID REQUIRING PROLONGED OBSERVATION; SYSTEMIC LUPUS; LONG-TERM; PROGNOSTIC FACTORS; ERYTHEMATOSUS SLE; BIOPSY; CLASSIFICATION; GLOMERULONEPHRITIS; CHILDREN; CYCLOPHOSPHAMIDE AB Despite several years of intense investigation, there continues to be controversy about the value of clinical, demographic and histologic features in prediction of outcomes of lupus nephritis. In addition, contemporary treatments have reduced the risk of progressive renal injury and thus may have altered the prognostic significance of some of these factors. We have therefore re-examined the predictive value of variables previously associated with an increased risk of renal insufficiency by studying 65 patients with severe lupus nephritis treated with intensive regimens of intravenous pulse cyclophosphamide or methylprednisolone. Five clinical features at study entry were each associated with an increased probability of doubling the serum creatinine: age greater than 30 years, Black race, hematocrit less than 26%, serum creatinine greater than 2.4 mg/dl, and C3 complement less than 76 mg/dI. By multivariate survival analysis, serum creatinine, hematocrit and race emerged as the strongest set of independent clinical predictors; the other clinical and demographic factors, including age and C3 complement did not contribute significantly to outcome predictions in the context of these three variables. Renal biopsy evaluation offered additional prognostic information and showed that patients with severe active and chronic histologic changes were at increased risk for developing renal insufficiency. The combination of cellular crescents and interstitial fibrosis was particularly ominous. Outcome predictions based on the strongest clinical model (serum creatinine, hematocrit and race) were significantly enhanced by the addition of renal pathology data. Consideration of these prognostic factors may contribute to decisions regarding the type and intensity of immunosuppressive therapy for patients with lupus nephritis. C1 NIH,CTR CLIN,DEPT NURSING,BETHESDA,MD 20892. RP AUSTIN, HA (reprint author), NIDDKD,KIDNEY DIS SECT,BLDG 10,ROOM 3N-112,BETHESDA,MD 20892, USA. NR 60 TC 234 Z9 240 U1 0 U2 3 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 1994 VL 45 IS 2 BP 544 EP 550 DI 10.1038/ki.1994.70 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA MR136 UT WOS:A1994MR13600033 PM 8164443 ER PT J AU HOFFMAN, A GROSSMAN, E GOLDSTEIN, DS GILL, JR KEISER, HR AF HOFFMAN, A GROSSMAN, E GOLDSTEIN, DS GILL, JR KEISER, HR TI URINARY-EXCRETION RATE OF ENDOTHELIN-1 IN PATIENTS WITH ESSENTIAL-HYPERTENSION AND SALT SENSITIVITY SO KIDNEY INTERNATIONAL LA English DT Article ID CELLS; PLASMA; IMMUNOREACTIVITY AB To assess the possible role of ET-1 in the pathogenesis of hypertension and salt sensitivity levels of immunoreactive endothelin-1 (irET-1) were measured in plasma and urine of 17 patients with essential hypertension and in 19 normotensive control subjects. Effects of alterations in dietary sodium content on urinary irET-1 levels also were assessed. Plasma levels of irET-1 did not differ between the hypertensives and normotensive groups (1.1 +/- 0.3 and 1.3 +/- 0.1 pg/ml). Urine samples of both groups contained high concentrations of irET-1. However, the mean daily urinary excretion of irET-1 in the hypertensives was less than one-third that in controls (29 +/- 3 vs. 109 +/- 21 ng/day, respectively, P < 0.01). Changing dietary sodium content in the hypertensives had no effect on mean irET-1 excretion. However, on either low, intermediate, or high salt diet, ''salt sensitive'' hypertensives had lower levels of the peptide than ''salt resistant'' patients (23 +/- 3 vs. 36 +/- 5 ng/day, respectively, P < 0.05). The data demonstrate a marked reduction in irET-1 excretion in patients with essential hypertension, despite normal plasma levels of the peptide. Since ET-1 has diuretic and natriuretic properties, the decreased renal excretion of ET-1 may be of relevance to the pathophysiology of hypertension and salt sensitivity. C1 TECHNION ISRAEL INST TECHNOL,HAIFA,ISRAEL. NHLBI,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20892. RP HOFFMAN, A (reprint author), RAMBAN MED CTR,DEPT SURG,TRANSPLANT UNIT,IL-31096 HAIFA,ISRAEL. NR 22 TC 61 Z9 62 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 1994 VL 45 IS 2 BP 556 EP 560 DI 10.1038/ki.1994.72 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA MR136 UT WOS:A1994MR13600035 PM 8164445 ER PT J AU PETEN, EP YANG, CW STRIKER, GE STRIKER, LJ AF PETEN, EP YANG, CW STRIKER, GE STRIKER, LJ TI GENE ACTIVATION IN GLOMERULOSCLEROSIS - A ROLE FOR GROWTH-PROMOTING HORMONES SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT Satellite Symposium on Progression of Renal Disease CY JUN 20-22, 1993 CL TIBERIAS, ISRAEL ID POLYMERASE CHAIN-REACTION; MESSENGER-RNA; EXTRACELLULAR-MATRIX; TRANSGENIC MICE; CELL TURNOVER; IV COLLAGEN; EXPRESSION; SCLEROSIS; GLOMERULI C1 NIDDK,RENAL CELL BIOL SECT,BETHESDA,MD 20892. NR 21 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 1994 VL 45 SU 45 BP S48 EP S50 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA MR867 UT WOS:A1994MR86700013 PM 8158897 ER PT J AU STRIKER, GE AF STRIKER, GE TI CELLULAR MECHANISMS OF GLOMERULAR INJURY-I - SUMMARY AND CONCLUDING REMARKS SO KIDNEY INTERNATIONAL LA English DT Editorial Material RP STRIKER, GE (reprint author), NIDDK,DIV KIDNEY UROL & HEMATOL DIS,9000 ROCKVILLE PIKE,BLDG 10,ROOM 3N110,BETHESDA,MD, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 1994 VL 45 SU 45 BP S56 EP S57 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA MR867 UT WOS:A1994MR86700016 ER PT J AU VLASSARA, H BUCALA, R STRIKER, L AF VLASSARA, H BUCALA, R STRIKER, L TI PATHOGENIC EFFECTS OF ADVANCED GLYCOSYLATION - BIOCHEMICAL, BIOLOGIC, AND CLINICAL IMPLICATIONS FOR DIABETES AND AGING SO LABORATORY INVESTIGATION LA English DT Review ID NON-ENZYMATIC GLYCOSYLATION; GLUCOSE-MODIFIED PROTEINS; HUMAN-SERUM-ALBUMIN; LOW-DENSITY LIPOPROTEINS; SURFACE BINDING-PROTEIN; GROWTH FACTOR-I; END-PRODUCTS; NONENZYMATIC GLYCOSYLATION; MAILLARD REACTION; LENS PROTEINS C1 NIDDK,MDB,RENAL CELL BIOL SECT,BETHESDA,MD. RP VLASSARA, H (reprint author), PICOWER INST MED RES,350 COMMUNITY DR,MANHASSET,NY 11030, USA. NR 130 TC 763 Z9 803 U1 3 U2 11 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 1994 VL 70 IS 2 BP 138 EP 151 PG 14 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA NB691 UT WOS:A1994NB69100002 PM 8139257 ER PT J AU MILLER, CJ VOGEL, P ALEXANDER, NJ DANDEKAR, S HENDRICKX, AG MARX, PA AF MILLER, CJ VOGEL, P ALEXANDER, NJ DANDEKAR, S HENDRICKX, AG MARX, PA TI PATHOLOGY AND LOCALIZATION OF SIMIAN IMMUNODEFICIENCY VIRUS IN THE REPRODUCTIVE-TRACT OF CHRONICALLY INFECTED MALE RHESUS MACAQUES SO LABORATORY INVESTIGATION LA English DT Article DE GENITAL TRACT; LANGERHANS CELL; HIV TRANSMISSION ID IMMUNE-DEFICIENCY-SYNDROME; SEXUAL TRANSMISSION; PREEJACULATORY FLUID; SEROPOSITIVE MEN; TYPE-1; FEMALE; MONKEYS; SEMEN; AIDS; CELLS AB BACKGROUND: Despite the fact that human immunodeficiency virus (HIV) is transmitted by sexual contact, the biology of this mode of transmission remains largely undefined. HIV is present in semen in both cell-free and cell-associated forms and can be isolated from asymptomatic individuals and AIDS patients. The source of HIV in semen and the target cells for HIV transmission to men are unknown. Epidemiologic studies have shown that in men, the presence of an intact foreskin is associated with increased risk of HIV infection. EXPERIMENTAL DESIGN: The reproductive tracts from 13 chronically simian immunodeficiency virus (SIV)-infected adult male rhesus macaques were examined for this study. Routine histologic examination was undertaken to characterize the reproductive tract pathology. In situ hybridization and immunohistochemistry were used to localize SIV-infected cells and determine the immunophenotype of inflammatory infiltrates. RESULTS: SIV-infected cells (macrophages, T cells) were found at all levels of the reproductive tract and were commonly associated with inflammatory lesions. Infected cells were found most consistently in the epididymis. In one animal, SIV-infected cells (presumably Langerhans cells) were present in the stratified squamous epithelium of the foreskin. Testicular atrophy and degeneration were relatively common findings. The most common lesion in the accessory glands was mild lymphocytic inflammation. In addition, atrophy of the glandular elements and interstitial fibrosis in the prostate gland were found, One animal had a granulomatous epididymitis with multinucleate giant cells that may have been a primary SIV lesion. CONCLUSIONS: The reproductive tract pathology in chronically SIV-infected male rhesus macaques and AIDS patients is similar. SIV-infected cells can be found at all levels of the male rhesus macaque reproductive tract and SIV can infect cells in the mucosal epithelium of the foreskin. This latter finding indicates that target cells for HIV transmission may be present in the foreskin epithelium of uncircumcised men. C1 UNIV CALIF DAVIS,SCH MED,DEPT INTERNAL MED,DAVIS,CA 95616. NICHHD,BETHESDA,MD 20892. RP MILLER, CJ (reprint author), UNIV CALIF DAVIS,SCH VET MED,DEPT VET PATHOL MICROBIOL & IMMUNOL,CALIF REG PRIMATE RES CTR,DAVIS,CA 95616, USA. FU NCRR NIH HHS [RR00169] NR 32 TC 62 Z9 62 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 1994 VL 70 IS 2 BP 255 EP 262 PG 8 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA NB691 UT WOS:A1994NB69100014 PM 8139266 ER PT J AU YELLON, RF ROSE, E KENNA, MA DOYLE, WJ CASSELBRANT, M DIVEN, WF WHITESIDE, TL SWARTS, JD HEYES, MP AF YELLON, RF ROSE, E KENNA, MA DOYLE, WJ CASSELBRANT, M DIVEN, WF WHITESIDE, TL SWARTS, JD HEYES, MP TI SENSORINEURAL HEARING-LOSS FROM QUINOLINIC ACID - A NEUROTOXIN IN MIDDLE-EAR EFFUSIONS SO LARYNGOSCOPE LA English DT Article ID ROUND WINDOW MEMBRANE; GUINEA-PIG COCHLEA; OTITIS-MEDIA; CEREBROSPINAL-FLUID; HUMAN MACROPHAGES; L-KYNURENINE; AMINO-ACIDS; INNER-EAR; NEUROTRANSMISSION; BRAIN AB Quinolinic acid (QUIN) is an endogenous metabolite that exerts a neurotoxic effect by binding to specific neuronal receptors. Studies involving a broad spectrum of infectious and inflammatory central nervous system diseases have suggested a role for QUIN in causing neuronal injury. Since there is evidence for presence of the QUIN receptor in mammalian cochleas, QUIN was measured in middle ear effusions (MEEs). Gas chromatography/mass spectrometry detected QUIN in each of 65 diluted human MEEs, with a mean of 482 +/- 75 (SEM) nmol/L and a range from 15 to 2667 nmol/L. QUIN was also detected in each of 197 chinchilla MEEs from five different models of otitis media, with a mean of 10.6 +/- 1.3 (SEM) mu mol/L and a range from 0.23 to 146.0 mu mol/L (corrected for dilution). To determine whether QUIN causes sensorineural hearing loss (SNHL), QUIN solutions were placed on round window membranes (RWM) for 20 to 240 minutes, in 20 chinchillas. SNHL was detected by electocochleography in QUIN-exposed animals, but not in saline controls. We conclude that QUIN is present in MEEs and that QUIN in the middle ear has the potential to cross the RWM and cause sensorineural hearing loss, possibly by binding to specific neuronal receptors in mammalian cochleas. C1 UNIV PITTSBURGH,SCH MED,PITTSBURGH CANC INST,DEPT OTOLARYNGOL,DIV PEDIAT OTOLARYNGOL,PITTSBURGH,PA 15213. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. UNIV PITTSBURGH,SCH MED,PITTSBURGH CANC INST,DEPT PATHOL,PITTSBURGH,PA 15213. RP YELLON, RF (reprint author), UNIV PITTSBURGH,CHILDRENS HOSP PITTSBURGH,SCH MED,DEPT PEDIAT OTOLARYNGOL,1 CHILDRENS PL,PITTSBURGH,PA 15213, USA. FU NIDCD NIH HHS [DC00021, DC01260] NR 37 TC 11 Z9 15 U1 0 U2 0 PU LARYNGOSCOPE CO PI ST LOUIS PA 10 S BROADWAY 14TH FLOOR, ST LOUIS, MO 63102-1741 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD FEB PY 1994 VL 104 IS 2 BP 176 EP 181 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA MV778 UT WOS:A1994MV77800009 PM 8302120 ER PT J AU SCHLAIFER, D MEYER, K MULLER, C ATTAL, M SMITH, MT TAMAKI, S WEIMELS, J PRIS, J JAFFREZOU, JP LAURENT, G MYERS, CE AF SCHLAIFER, D MEYER, K MULLER, C ATTAL, M SMITH, MT TAMAKI, S WEIMELS, J PRIS, J JAFFREZOU, JP LAURENT, G MYERS, CE TI ANTISENSE INHIBITION OF MYELOPEROXIDASE INCREASES THE SENSITIVITY OF THE HL-60 CELL-LINE TO VINCRISTINE SO LEUKEMIA LA English DT Note AB Myeloperoxidase (MPO), a heme-peroxidase found in the HL-60 myeloblastic cell line, is involved in vincristine (VCR) metabolism and the inactivation of this drug. We have examined whether decreased MPO activity correlated with increased sensitivity to VCR toxicity in myeloid leukemia cells. We have used MPO antisense RNA to reduce 60% of the MPO activity in the HL-60 cells. The MPO-deficient HL-60 cell line, C15, was significantly more sensitive to VCR than the parental MPO-positive cell line. Both cell lines were negative for P170-glycoprotein expression. Conversely, an MPO-positive C15 subclone was more resistant to VCR than the MPO-deficient C15 cell line. No significant differences in cytotoxic effects were observed between MPO-positive and MPO-deficient cells, following treatment with either daunorubicin or actinomycin D, two multidrug resistance-related drugs. These results strongly support an important role for MPO in VCR resistance in HL-60 cells. Antisense manipulation of the MPO content of myeloid cells could be of potential interest in leukemia treatment. C1 CHU PURPAN,DEPT HEMATOL,TOULOUSE,FRANCE. NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. UNIV CALIF BERKELEY,SCH PUBL HLTH,BERKELEY,CA 94720. RI MULLER, Catherine/E-2060-2011 NR 7 TC 15 Z9 16 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD FEB PY 1994 VL 8 IS 2 BP 289 EP 291 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA MZ599 UT WOS:A1994MZ59900012 PM 7905941 ER PT J AU VANGELDEREN, P DEVLEESCHOUWER, MHM DESPRES, D PEKAR, J VANZIJL, PCM MOONEN, CTW AF VANGELDEREN, P DEVLEESCHOUWER, MHM DESPRES, D PEKAR, J VANZIJL, PCM MOONEN, CTW TI WATER DIFFUSION AND ACUTE STROKE SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE DIFFUSION IMAGING; STROKE; MR; DIFFUSION ANISOTROPY ID CEREBRAL-ISCHEMIA; T2-WEIGHTED MRI; RAT-BRAIN; CAT BRAIN; NMR; GRADIENT; SPECTROSCOPY; PERFUSION; SYSTEM; CELLS AB The occlusion of the middle cerebral artery was used as an experimental acute stroke model in 30 cats. The diffusion of water was followed by diffusion-sensitized MRI between 1 and 15 h after induction of stroke. It is demonstrated that images representing the trace of the diffusion tenser provide a much more accurate delineation of affected area than images representing the diffusion in one direction only. The reason is that the strong contrast caused by the anisotropy and orientation of myelin fibers is completely removed in the trace of the diffusion tenser. The trace images show a small contrast between white and gray matter. The diffusion coefficient of white matter is decreased in acute stroke to approximately the same extent as gray matter. It is further shown that the average lifetime of water in extra and intracellular space is shorter than 20 ms both for healthy and ischemic tissue indicating that myelin fibers are permeable to water. The anisotropy contrast did not change before or after induction of stroke, nor after sacrifice. Together, these observations are consistent with the view that the changes in water diffusion during acute stroke are directly related to cytotoxic oedema, i.e., to the change in relative volume of intra- and extracellular spaces. Changes in membrane permeability do not appear to contribute significantly to the changes in diffusion. C1 NIH,NCRR,BEIP,IN VIVO NMR RES CTR,BETHESDA,MD 20892. DELFT UNIV TECHNOL,FAC APPL PHYS,DELFT,NETHERLANDS. JOHNS HOPKINS UNIV,SCH MED,DEPT RADIOL,BALTIMORE,MD 21205. RI van Zijl, Peter/B-8680-2008 FU NINDS NIH HHS [1RO1 NS31490-01] NR 33 TC 319 Z9 318 U1 0 U2 10 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD FEB PY 1994 VL 31 IS 2 BP 154 EP 163 DI 10.1002/mrm.1910310209 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA MU243 UT WOS:A1994MU24300008 PM 8133751 ER PT J AU YOUNG, MF IBARAKI, K KERR, JM LYU, MS KOZAK, CA AF YOUNG, MF IBARAKI, K KERR, JM LYU, MS KOZAK, CA TI MURINE BONE SIALOPROTEIN (BSP) - CDNA CLONING, MESSENGER-RNA EXPRESSION, AND GENETIC-MAPPING SO MAMMALIAN GENOME LA English DT Note ID MINERALIZED-TISSUE FORMATION; SECRETED PHOSPHOPROTEIN-1; MESSENGER-RNA; RECEPTOR; CELLS; LOCALIZATION; BIOSYNTHESIS; OSTEOPONTIN; ASSOCIATION; PROTEINS C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. RP YOUNG, MF (reprint author), NIDR,BONE RES BRANCH,SKELETAL MATRIX SECT,BETHESDA,MD 20892, USA. NR 25 TC 94 Z9 95 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 FEB PY 1994 VL 5 IS 2 BP 108 EP 111 DI 10.1007/BF00292337 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA MU085 UT WOS:A1994MU08500006 PM 8180469 ER PT J AU LOSSIE, AC VANDENBERGH, DJ UHL, GR CAMPER, SA AF LOSSIE, AC VANDENBERGH, DJ UHL, GR CAMPER, SA TI LOCALIZATION OF THE DOPAMINE TRANSPORTER GENE, DAT1, ON MOUSE CHROMOSOME-13 SO MAMMALIAN GENOME LA English DT Note ID MICE C1 UNIV MICHIGAN,DEPT HUMAN GENET,ANN ARBOR,MI 48109. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. NATL INST DRUG ABUSE,ADDICT RES CTR,MOLEC NEUROBIOL LAB,BALTIMORE,MD 21224. RI Lossie, Amy/D-2480-2009; OI Lossie, Amy/0000-0001-5078-7743; Camper, Sally/0000-0001-8556-3379 FU NICHD NIH HHS [1R01-HD26490-010A] NR 10 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD FEB PY 1994 VL 5 IS 2 BP 117 EP 118 DI 10.1007/BF00292340 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA MU085 UT WOS:A1994MU08500009 PM 8180472 ER PT J AU GONZALEZFERNANDEZ, JM ERMENTROUT, B AF GONZALEZFERNANDEZ, JM ERMENTROUT, B TI ON THE ORIGIN AND DYNAMICS OF THE VASOMOTION OF SMALL ARTERIES SO MATHEMATICAL BIOSCIENCES LA English DT Review ID SMOOTH-MUSCLE CELLS; ACTIVATED POTASSIUM CHANNELS; RABBIT EAR ARTERY; SPONTANEOUSLY HYPERTENSIVE RATS; MESENTERIC RESISTANCE VESSELS; MIDDLE CEREBRAL-ARTERY; CALCIUM CHANNELS; SKELETAL-MUSCLE; WHOLE-CELL; MYOSIN PHOSPHORYLATION AB A system of differential equations describing stationary vasomotion is formulated. It incorporates the ionic transports, cell-membrane potential, muscle contraction of the vessel smooth muscle cells, and the mechanics of a thick-walled cylinder. It is shown that the interaction of Ca2+ and K+ fluxes mediated by voltage-gated and voltage-calcium-gated channels, respectively, brings about periodicity of those transports. This results on a time-periodic cytoplasmic calcium concentration, myosin light chains phosphorylation, and crossbridges formation with the attending muscle stress. The vessel's transmural pressure determines a hoop stress. The resultant hoop, elastic, and muscle stresses determine the rate of change of the vessel's diameter: vasomotion. The model results agree with the experimental observations. The sensitivity of the vasomotion's dependence on parameter values and its significance to experimental protocols are examined. Further, it is hypothesized that the dependence of calcium-channel openings on voltage is shifted by changes on transmural pressure. Thus, Harder's experimental results are reproduced, among them the decreasing of vessel diameter with increasing pressure. Those behaviors are associated with a pattern of change of the singularities of the system of equations describing the model. This suggests a functional relationship on the interactions of Ca-2 + and K+ fluxes responsible for the myogenic response; it may not result from a single molecular mechanism. The model is constructed so that additional experimental information can be readily incorporated. C1 UNIV PITTSBURGH,DEPT MATH,PITTSBURGH,PA 15260. RP GONZALEZFERNANDEZ, JM (reprint author), NIDDK,MATH RES BRANCH,BETHESDA,MD 20892, USA. NR 104 TC 41 Z9 42 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0025-5564 J9 MATH BIOSCI JI Math. Biosci. PD FEB PY 1994 VL 119 IS 2 BP 127 EP 167 DI 10.1016/0025-5564(94)90074-4 PG 41 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA NN421 UT WOS:A1994NN42100001 PM 8142694 ER PT J AU MCFALL, SL WARNECKE, RB KALUZNY, AD AITKEN, M FORD, L AF MCFALL, SL WARNECKE, RB KALUZNY, AD AITKEN, M FORD, L TI PHYSICIAN AND PRACTICE CHARACTERISTICS ASSOCIATED WITH JUDGMENTS ABOUT BREAST-CANCER-TREATMENT SO MEDICAL CARE LA English DT Article DE PRACTICE CHARACTERISTICS; BREAST CANCER; CANCER TREATMENT; MEDICAL DECISION; PHYSICIAN SPECIALTIES ID TOTAL MASTECTOMY; CLINICAL-TRIALS AB Since most cancer is treated in the local community, the judgments of primary care physicians about treatment of breast cancer are important. This study examined physician and practice characteristics associated with physician judgments about the treatment of Stage I and Stage II breast cancer. Data are combined from samples of 3,436 physicians: physicians affiliated with hospitals participating in the Community Clinical Oncology Program (CCOP) and a national sample of non-CCOP physicians. This study focused on 1,460 physicians who had seen breast cancer patients and participated in treatment decision-making. Judgments were elicited using brief vignettes. Judgments were more variable for Stage I than for Stage II treatments. Judgments consistent with the NIH Consensus Conferences on breast cancer were more likely from surgeons, physicians who participated in information networks focused on cancer, and those with more breast cancer patients. Concurrence with the consensus conference positions was less likely in older physicians and those in solo practice. These findings point to structures that reinforce quality of care, particularly those that enhance communication, such as group practice or the activities of hospital staffs, information networks, and organized continuing education. C1 CREIGHTON UNIV,SCH PHARM & ALLIED HLTH,OMAHA,NE 68178. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. UNIV ILLINOIS,SURVEY RES LAB,CHICAGO,IL. UNIV ILLINOIS,DEPT SOCIOL,CHICAGO,IL 60680. UNIV N CAROLINA,SCH PUBL HLTH,CECIL G SHEPS CTR HLTH SERV RES,CHAPEL HILL,NC. UNIV N CAROLINA,SCH PUBL HLTH,DEPT HLTH POLICY & ADM,CHAPEL HILL,NC. RP MCFALL, SL (reprint author), UNIV OKLAHOMA,HLTH SCI CTR,DEPT HLTH PROMOT SCI,POB 26901,OKLAHOMA CITY,OK 73190, USA. NR 26 TC 31 Z9 31 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD FEB PY 1994 VL 32 IS 2 BP 106 EP 117 DI 10.1097/00005650-199402000-00002 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA MV785 UT WOS:A1994MV78500002 PM 8302103 ER PT J AU GANDJBAKHCHE, AH NOSSAL, R BONNER, RF AF GANDJBAKHCHE, AH NOSSAL, R BONNER, RF TI RESOLUTION LIMITS FOR OPTICAL TRANSILLUMINATION OF ABNORMALITIES DEEPLY EMBEDDED IN TISSUES SO MEDICAL PHYSICS LA English DT Article DE RANDOM WALKS; OPTICAL IMAGING; SPATIAL RESOLUTION ID SPATIAL-RESOLUTION; PHOTON MIGRATION; TIME; MEDIA AB Random walk theory is used to calculate the line spread function (LSF) of photons as they cross the midplane of a slab of finite thickness. The relationship between the LSF and the photon transit time in transillumination time-resolved experiments is investigated. It is found that the LSF is approximately Gaussian distributed, with a standard deviation, sigma, which can be used as a criterion of the spatial resolution of the imaging system. Results are substantiated by comparison with actual data in the literature. Any given resolution can be improved by reducing the excess transit time Delta t, but heterogeneity of the scattering medium and low levels of detected light enormously complicate the achievement of subcentimeter spatial resolution. The latter point is discussed by using optical parameters of breast tissues for visible and near-infrared radiation (NIR) light. RP GANDJBAKHCHE, AH (reprint author), NIH,PHYS SCI LAB,DIV COMP RES & TECHNOL,BETHESDA,MD 20892, USA. RI Bonner, Robert/C-6783-2015 NR 24 TC 86 Z9 86 U1 0 U2 1 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0094-2405 J9 MED PHYS JI Med. Phys. PD FEB PY 1994 VL 21 IS 2 BP 185 EP 191 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA MX077 UT WOS:A1994MX07700002 PM 8177151 ER PT J AU SALIVE, ME AF SALIVE, ME TI EVALUATION OF AGING PILOTS - EVIDENCE, POLICY, AND FUTURE-DIRECTIONS SO MILITARY MEDICINE LA English DT Article AB Current Federal Aviation Administration (FAA) regulations require that pilots of large commercial passenger and cargo aircraft be under age 60. However, the requirement does not apply to other pilots and the courts have ruled that mandatory retirement of test pilots at age 60 violates the Age Discrimination in Employment Act. FAA medical standards establish three levels of medical qualification, which require certain age-specific screening tests. This paper reviews the epidemiologic and clinical evidence relevant to the evaluation of aging pilots. This evidence is compared and contrasted with the current FAA requirements and past recommendations of the American Medical Association, the Institute of Medicine, and the Office of Technology Assessment. An opportunity exists to assess the class I examination and other tests through the consent decree covering aging test pilots. Another course of action would be to implement special issuances for older pilots. RP SALIVE, ME (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,7201 WISCONSIN AVE,GATEWAY BLDG,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0026-4075 J9 MIL MED JI Milit. Med. PD FEB PY 1994 VL 159 IS 2 BP 83 EP 86 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA NB549 UT WOS:A1994NB54900001 PM 8202253 ER PT J AU GRIGIONI, WF DERRICO, A FORTUNATO, C FIORENTINO, M MANCINI, AM STETLERSTEVENSON, WG SOBEL, ME LIOTTA, LA ONISTO, M GARBISA, S AF GRIGIONI, WF DERRICO, A FORTUNATO, C FIORENTINO, M MANCINI, AM STETLERSTEVENSON, WG SOBEL, ME LIOTTA, LA ONISTO, M GARBISA, S TI PROGNOSIS OF GASTRIC-CARCINOMA REVEALED BY INTERACTIONS BETWEEN TUMOR-CELLS AND BASEMENT-MEMBRANE SO MODERN PATHOLOGY LA English DT Article DE BASEMENT MEMBRANE-RELATED ANTIGENS; TIMP-2; GASTRIC CARCINOMA ID LAMININ RECEPTOR; HEPATOCELLULAR-CARCINOMA; INCREASED EXPRESSION; IV COLLAGENASE; HUMAN COLON; CANCER; ALPHA-2-MACROGLOBULIN; ANTIGENS; TIMP-2 AB The extra-cellular matrix (ECM) related antigens, type IV collagen, laminin, M(r) 68,000 laminin receptor (LR), M(r) 72,000 type IV collagenase (MMP-2), its inhibitor TIMP-2, and alpha 2-macroglobulin expression have been immunohistochemically investigated in 100 cases of human gastric carcinoma with a 5-yr follow up. Basement membranes were inversely related to tumoral differentiation. At the early intramucosal stage of both intestinal and diffuse histological types, TIMP-2 was expressed by the majority of tumor cells (60/63%), whereas MMP-2+ and LR+ cells were in the minority (24/19%, 23/0%, respectively). At the early submucosal stage, TIMP-2+ cells moderately decreased in both histological types (49/49%), whereas a consistently higher number of both MMP-2+and LR+ cells were detected only in the diffuse carcinomas (72%). In the advanced stage, the expression of TIMP-2 further declined (22/24%), although the other two antigens increased or mantained high levels of expression. AMG+ cells never exceeded 10% in either histological type at any stage. In the liver metastases, both MMP-2+ and LR+ cells were more numerous than in the primary tumor (P < 0.002 and P < 0.01). Patients who died from their primary tumor had higher percentages of LR+, MMP-2+, and AMG+ cells and lower percentages of TIMP-2+ cells with respect to survivors. We believe evaluation of ECM-related antigens, and especially TIMP-2, may help determine a confident prognosis for gastric cancer. C1 MED SCH BOLOGNA,INST PATHOL,BOLOGNA,ITALY. NIH,PATHOL LAB,BETHESDA,MD 20892. UNIV PADUA,INST HISTOL & GEN EMBRIOL,PADUA,ITALY. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 28 TC 88 Z9 92 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 FEB PY 1994 VL 7 IS 2 BP 220 EP 225 PG 6 WC Pathology SC Pathology GA NF428 UT WOS:A1994NF42800015 PM 8008747 ER PT J AU KASLOW, DC HUI, G KUMAR, S AF KASLOW, DC HUI, G KUMAR, S TI EXPRESSION AND ANTIGENICITY OF PLASMODIUM-FALCIPARUM MAJOR MEROZOITE SURFACE PROTEIN (MSP1(19)) VARIANTS SECRETED FROM SACCHAROMYCES-CEREVISIAE SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE MALARIA; MEROZOITE SURFACE PROTEIN; ANTIGENIC DIVERSITY; VACCINE ID ANTIBODIES; MALARIA; FRAGMENT; PRECURSOR; PARASITE; DOMAINS; GROWTH AB Four antigenic variants of the 19-kDa carboxy terminal fragment of Plasmodium falciparum merozoite surface protein, MSP1 (MSP1(19)), were expressed in Saccharomyces cerevisiae as a histidine-tagged, secreted polypeptides (rMSP1(19)s). Structural analysis of the rMSP1(19)s indicated that a single amino acid change (E to Q) in the first EGF-like domain of the yeast-secreted rMSP1(19) proteins caused a significant change in their disulfide bond-dependent conformation. The antigenicity of the rMSP1(19)s were qualitatively and quantitatively analyzed by direct and competitive binding ELISAs. The data indicate that conserved and variant B cell determinants of MSP1(19), as well as epitopes that are known targets of protective antibodies, were recreated authentically in the rMSP1(19)s. Secretion of histidine-tagged rMSP1(19)s using the expression system described may be an efficient and effective means of producing a properly folded immunogen for a human vaccine against the blood stages of P. falciparum. C1 NIAID,MALARIA RES LAB,BETHESDA,MD 20892. UNIV HAWAII MANOA,JOHN A BURNS SCH MED,DEPT TROP MED & MED MICROBIOL,HONOLULU,HI. RP KASLOW, DC (reprint author), NIAID,MOLEC VACCINE SECT,BLDG 4,ROOM B1-37,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [AI30589] NR 17 TC 80 Z9 83 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD FEB PY 1994 VL 63 IS 2 BP 283 EP 289 DI 10.1016/0166-6851(94)90064-7 PG 7 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA MZ432 UT WOS:A1994MZ43200011 PM 7516493 ER PT J AU BEELER, JF LAROCHELLE, WJ CHEDID, M TRONICK, SR AARONSON, SA AF BEELER, JF LAROCHELLE, WJ CHEDID, M TRONICK, SR AARONSON, SA TI PROKARYOTIC EXPRESSION CLONING OF A NOVEL HUMAN TYROSINE KINASE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SERINE THREONINE KINASE; PROTEIN-KINASE; PHOSPHOTYROSINE ANTIBODY; CONSERVED FEATURES; PHOSPHORYLATION; FAMILY; IDENTIFICATION; PHOSPHATASE; LIBRARIES; MEMBERS AB Screening of a human embryonic lung fibroblast cDNA expression library with antiphosphotyrosine antibodies led to isolation of a novel protein kinase. A clone, designated A6, contained a 3-kb cDNA insert with a predicted open reading frame of 350 amino acids. DNA sequence analysis failed to reveal any detectable similarity with previously known genes, and the predicted A6 protein lacked any of the motifs commonly conserved in the catalytic domains of protein kinases. However, the bacterially expressed beta-galactosidase-A6 fusion protein demonstrated both tyrosine and serine phosphorylation in an in vitro kinase assay and phosphorylated exogenous substrates including myelin basic protein specifically on tyrosine residues. The enzyme also displayed biochemical properties analogous to those of other protein tyrosine kinases. The A6 gene was found to be expressed widely at the transcript level in normal tissues and was evolutionarily conserved. Thus, A6 represents a novel tyrosine kinase which is highly divergent from previously described members of this important class of regulatory molecules. C1 NCI, CELLULAR & MOLEC BIOL LAB, BETHESDA, MD 20892 USA. NR 29 TC 38 Z9 39 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1994 VL 14 IS 2 BP 982 EP 988 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NK734 UT WOS:A1994NK73400013 PM 7507208 ER PT J AU BEECHAM, EJ JONES, GM LINK, C HUPPI, K POTTER, M MUSHINSKI, JF BOHR, VA AF BEECHAM, EJ JONES, GM LINK, C HUPPI, K POTTER, M MUSHINSKI, JF BOHR, VA TI DNA-REPAIR DEFECTS ASSOCIATED WITH CHROMOSOMAL TRANSLOCATION BREAKSITE REGIONS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HAMSTER OVARY CELLS; CYCLOBUTANE PYRIMIDINE DIMERS; DIHYDROFOLATE-REDUCTASE GENE; STRAND-SPECIFIC REPAIR; IONIZING-RADIATION; TRANSCRIBED STRAND; V(D)J RECOMBINATION; PVT-1 TRANSCRIPTS; SCID MUTATION; ACTIVE GENE AB Using an assay that measures the removal of UV-induced pyrimidine dimers in specific DNA sequences, we have found that the Pvt-1, immunoglobulin H-C alpha (IgH-C alpha), and IgL-kappa loci are poorly repaired in normal B lymphoblasts from plasmacytoma-susceptible BALB-cAnPt mice. Breaksites in these genes are associated with the chromosomal translocations that are found in >95% of BALB-cAnPt plasmacytomas. In contrast to those from BALB/cAnPt mice, B lymphoblasts from plasmacytoma-resistant DBA-2N mice rapidly repair Pvt-1, IgH-C alpha, and IgL-kappa. Further, (BALB/cAnPt x DBA/2N)F-1 hybrids, which are resistant to plasmacytoma development, carry an efficient (DBA/2N-like) repair phenotype. Analysis of allele-specific repair in the IgH-C alpha locus indicates that efficient repair is controlled by dominant, trans-acting factors. In the F-1 heterozygotes, these factors promote efficient repair of BALB/cAnPt IgH-C alpha gen sequences. The same sequences are poorly repair in the BALB/cAnPt parental strain. Analysis of the strand specificity of repair indicates that both strand-selective and nonselective forms of repair determine repair efficiency at the gene level in nonimmortalized murine B lymphoblasts. C1 NIA,GENET MOLEC LAB,BALTIMORE,MD 21224. NCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NCI,GENET LAB,BETHESDA,MD 20892. NR 37 TC 15 Z9 15 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1994 VL 14 IS 2 BP 1204 EP 1212 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NK734 UT WOS:A1994NK73400036 PM 8289801 ER PT J AU LEE, YH YANO, M LIU, SY MATSUNAGA, E JOHNSON, PF GONZALEZ, FJ AF LEE, YH YANO, M LIU, SY MATSUNAGA, E JOHNSON, PF GONZALEZ, FJ TI A NOVEL CIS-ACTING ELEMENT CONTROLLING THE RAT CYP2D5 GENE AND REQUIRING COOPERATIVITY BETWEEN C/EBP-BETA AND AN SP1 FACTOR SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ENHANCER-BINDING-PROTEIN; MAMMALIAN-CELLS; TRANSCRIPTION; EXPRESSION; DNA; ACTIVATION; MECHANISMS; PROMOTER; SEQUENCE; TRANSFECTION AB The rat CYP2D5 gene encodes a cytochrome P450 and is expressed in liver cells. Its expression commences a few days after birth, and maximal mRNA levels are achieved when animals reach puberty. Transfection and DNA binding studies performed to investigate the mechanism controlling developmentally programmed, liver specific expression of CYP2D5. Transfection studies using a series of CYP2D5 upstream DNA chloramphenicol acetyltransferase gene fusion constructs identified a segment of DNA between nucleotides -55 and -156 that conferred transcriptional activity in HepG2 cells. Activity was markedly increased by cotransfection with a vector expressing C/EBP beta but was unaffected by vectors producing other liver-enriched transcription factors (C/EBP alpha, HNF-1 alpha and DBP). DNase I footprinting revealed a region protected by both HepG2 and liver cell nuclear extracts between nucleotides -83 and -112. This region displayed some sequence similarity to the Sp1 consensus sequence and was able to bind the Sp1 protein, as assessed by a gel mobility shift assay. The role of Sp1 CYP2D5 transcription was confirmed by trans activation of the 2D5-CAT construct in Drosophila melanogaster cells by using an Sp1 expression vector. C/EBP beta alone was unable to directly bind the -83 to -112 region of the promoter but was able to produce a ternary complex when combined with HepG2 nuclear extracts or recombinant human Sp1. C/EBP alpha was unable to substitute for C/EBP beta in forming this ternary complex. A poor C/EBP binding site is present adjacent to the Sp1 site, and mutagenesis of this site abolished formation of the ternary complex with the CYP2D5 regulatory region. These results establish that two transcription factors can work in conjunction, possibly by protein-protein interaction, to activate the CYP2D5 gene. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,FREDERICK,MD 21702. RP LEE, YH (reprint author), NCI,MOLEC CARCINOGENESIS LAB,BLDG 37,RM 3E24,BETHESDA,MD 20892, USA. RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 FU PHS HHS [N01-C0-74101] NR 43 TC 114 Z9 116 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1994 VL 14 IS 2 BP 1383 EP 1394 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NK734 UT WOS:A1994NK73400053 PM 8289814 ER PT J AU PETRICOIN, E DAVID, M FANG, H GRIMLEY, P LARNER, AC POL, SV AF PETRICOIN, E DAVID, M FANG, H GRIMLEY, P LARNER, AC POL, SV TI HUMAN CANCER CELL FINES EXPRESS A NEGATIVE TRANSCRIPTIONAL REGULATOR OF THE INTERFERON REGULATORY FACTOR FAMILY OF DNA-BINDING PROTEINS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN PAPILLOMAVIRUS TYPE-16; VIRUS-40 LARGE-T; ADENOVIRUS E1A PROTEINS; FC-GAMMA RECEPTOR; ALPHA-INTERFERON; TYROSINE KINASE; GENE-EXPRESSION; FACTOR ISGF3; SIGNAL TRANSDUCTION; INVITRO ACTIVATION AB Members of the interferon regulatory factor (IRF) family of DNA binding transcription factors have roles in growth regulation, antiviral responses, and transcriptional induction of interferon (IFN)-activated early response genes. The IRF family member ISGF3 gamma is the DNA binding component of IFN-stimulated gene factor 3 (ISGF3), a multicomponent complex responsible for the stimulation of IFN-alpha-responsive genes. IFN-alpha-stimulated formation of ISGF3 and subsequent gene expression can be inhibited by phorbol esters or expression of the adenovirus E1A protein. We have investigated IFN signaling in human malignant tumor cell lines of the lung, colon, ovary, cervix, and hematopoietic organs and found some of these cells to be defective for IFN-alpha-induced formation of ISGF3. In many cases, an inhibitory activity termed transcriptional knockout (TKO) correlated with nonresponsiveness. TKO purified from a human papiliomavirus-negative cervical carcinoma cell line has a molecular size of 19 kDa. The purified protein interacted with the ISGF3 gamma component of ISGF3, preventing binding of ISGF3 to DNA. Purified TKO displaced ISGF3 from its DNA binding site in vitro and prevented ISGF3 gamma, IRF-1, and IRF-2 from interacting with the IFN-stimulated response element. Partially purified TKO can also directly interact with ISGF3 gamma in the absence of DNA. This protein may be involved with the development of malignancies and the inability of IFN to exert its antiproliferative and antiviral effects. C1 UNIFORMED SERV UNIV HLTH SCI,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT PATHOL,BETHESDA,MD 20892. NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892. NR 49 TC 33 Z9 33 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1994 VL 14 IS 2 BP 1477 EP 1486 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NK734 UT WOS:A1994NK73400063 PM 8289823 ER PT J AU DEERAUSQUIN, G BROOKER, G COSTA, E HANBAUER, I AF DEERAUSQUIN, G BROOKER, G COSTA, E HANBAUER, I TI PERSISTENT AMPA RECEPTOR STIMULATION ALTERS [CA2+](I) HOMEOSTASIS IN CULTURES OF EMBRYONIC DOPAMINERGIC-NEURONS SO MOLECULAR BRAIN RESEARCH LA English DT Article DE EXCITOTOXICITY; GLUTAMATE RECEPTOR; CALCIUM CHANNEL; FURA-2; CALCIUM; DOPAMINERGIC NEURON; PRIMARY CULTURE ID HIPPOCAMPAL PYRAMIDAL NEURONS; PROGRAMMED CELL-DEATH; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; CORTICAL CULTURE; CA-2+ CHANNELS; CA2+ CHANNELS; NEUROTOXICITY; GLUTAMATE; STRIATUM AB The effect of the ionotropic glutamate receptor agonist, AMPA, on intracellular Ca2+ concentrations ([Ca2+](i)) was studied in dopaminergic neurons present in primary cultures of ventral tegmental mesencephalon of 14 day rat embryos. Exposure of cells to 10 mu M AMPA for 1 min increased [Ca2+](i) by 2-3 fold in dopaminergic and other neurons and this response was obliterated within 5 min by superfusion with AMPA-free incubation buffer. In dopaminergic neurons, 1 min or 5 min exposure to 50 mu M AMPA increased [Ca2+](i) 3 to 5 times over control values. This rise in [Ca2+](i) persisted even after a 20 min superfusion with AMPA-free media, whereas, [Ca2+](i) in non-dopaminergic neurons was reversed to control Values during this time. Preincubation (2 min) of cultured cells with NBQX or the L-type channel blocker, nifedipine, but not with MK-801 blunted the rise of [Ca2+](i) in dopaminergic and other neurons. Pretreatment with 2 mu M NBQX Shifted the dose response curve for AMPA to the right without changing the basal [Ca2+](i). The presence of 10 mu M dantrolene, a blocker of Ca2+ release from intracellular stores, did not alter the initial rise of [Ca2+](i) elicited by 50 mu M AMPA, but prevented the destabilization of Ca2+ homeostasis by facilitating the recovery to normal of basal [Ca2+](i). Exposure to 50 mu M AMPA (5 min) caused an irreversible increase of[Ca2+](i) in dopaminergic neurons and cell death was manifested by propidium iodide uptake 6-7 h after AMPA exposure. The present results show that in dopaminergic neurons the increase of [Ca2+](i) elicited by activation of AMPA receptors is mediated by sustained Ca2+ flux through voltage-gated channels and through a Ca2+-dependent Ca2+ release from intracellular stores. Protracted stimulation of AMPA and kainate receptors caused death of dopaminergic neurons before that of other neurons present in the same culture. The increased vulnerability of dopaminergic neurons to AMPA may represent a mechanism of pathological relevance during ontogenesis. C1 NHLBI,CHEM PHARMACOL LAB,BETHESDA,MD 20892. GEORGETOWN UNIV,FIDIA GEORGETOWN INST NEUROSCI,WASHINGTON,DC 20007. RI de Erausquin, Gabriel/G-5840-2010 OI de Erausquin, Gabriel/0000-0001-6423-4461 NR 29 TC 21 Z9 21 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD FEB PY 1994 VL 21 IS 3-4 BP 303 EP 311 DI 10.1016/0169-328X(94)90261-5 PG 9 WC Neurosciences SC Neurosciences & Neurology GA MV342 UT WOS:A1994MV34200013 ER PT J AU DEBARTOLOMEIS, A AUSTIN, MC GOODWIN, GA SPEAR, LP PICKAR, D CRAWLEY, JN AF DEBARTOLOMEIS, A AUSTIN, MC GOODWIN, GA SPEAR, LP PICKAR, D CRAWLEY, JN TI DOPAMINERGIC AND PEPTIDERGIC MESSENGER-RNA LEVELS IN JUVENILE RAT-BRAIN AFTER PRENATAL COCAINE TREATMENT SO MOLECULAR BRAIN RESEARCH LA English DT Article DE STIMULANT; GENE REGULATION; DOPAMINE RECEPTOR; ENKEPHALIN; TYROSINE HYDROXYLASE; CHOLECYSTOKININ; DOPAMINE TRANSPORTER; IN SITU HYBRIDIZATION ID CHOLECYSTOKININ MESSENGER-RNA; CENTRAL-NERVOUS-SYSTEM; INSITU HYBRIDIZATION HISTOCHEMISTRY; LOCUS-CERULEUS NEURONS; TYROSINE-HYDROXYLASE; SUBSTANTIA NIGRA; ACOUSTIC STARTLE; GENE-EXPRESSION; EXPOSURE; TRANSPORTER AB The effects of prenatal cocaine treatment on gene expression in dopaminergic pathways of juvenile rats were investigated by in situ hybridization histochemistry. Pregnant rats from gestational day. 8 to 20 were administered one of the following treatments: (A) 40 mg/kg cocaine hydrochloride/3 ml/day s.c.; (B) 0.9% saline/3ml/day s.c. and pair fed to cocaine-exposed dams; (C) O.9% saline/3 ml/day s.c. and placement on cellulose-diluted diet to match the caloric intake of the cocaine-treated group without explicit food restriction; (D) no injection and lab chow diet. Levels of mRNA for the dopamine transporter, tyrosine hydroxylase, cholecystokinin, D-1 and D-2 dopamine receptors and enkephalin were quantitated in relevant dopaminergic regions of forebrain and midbrain of offspring that were sacrificed on postnatal day 21. Quantitative analysis revealed no significant changes in mRNA levels in any of the brain regions examined. In the present animal model, cocaine exposure in utero had no significant effect on mRNA levels of the dopamine transporter, D-1 or D-2 dopamine receptors, enkephalin, tyrosine hydroxylase, or cholecystokinin in juvenile rats. C1 NIMH,EXPTL THERAPEUT BRANCH,BEHAV NEUROPHARMACOL SECT,BETHESDA,MD 20892. SUNY BINGHAMTON,DEPT PSYCHOL,BINGHAMTON,NY 13901. UNIV PITTSBURGH,SCH MED,DEPT PSYCHIAT,PITTSBURGH,PA 15213. OI de Bartolomeis, Andrea/0000-0002-3188-5652 FU NIDA NIH HHS [NIDA K02-DA-00140, NIDA R01-DA-14478] NR 59 TC 29 Z9 29 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD FEB PY 1994 VL 21 IS 3-4 BP 321 EP 332 DI 10.1016/0169-328X(94)90263-1 PG 12 WC Neurosciences SC Neurosciences & Neurology GA MV342 UT WOS:A1994MV34200015 PM 7909578 ER PT J AU TACHIBANA, M ASANO, T WILCOX, E YOKOTANI, N RIVOLTA, MN FEX, J AF TACHIBANA, M ASANO, T WILCOX, E YOKOTANI, N RIVOLTA, MN FEX, J TI G-PROTEIN G(I2)ALPHA IN THE COCHLEA - CLONING AND SELECTIVE OCCURRENCE IN RECEPTOR-CELLS SO MOLECULAR BRAIN RESEARCH LA English DT Note DE G(I) PROTEIN; A SUBUNIT; CDNA LIBRARY; MOLECULAR CLONING; IMMUNOHISTOCHEMISTRY; AFFINITY-PURIFIED ANTIBODY; COCHLEA; INNER HAIR CELL; OUTER HAIR CELL ID GTP-BINDING PROTEIN; ADENYLATE-CYCLASE; SYSTEM; IDENTIFICATION; LOCALIZATION; TISSUES; LUNG; CDNA; RAT AB A cDNA library was made from the mouse cochlea and screened with a G protein-cDNA like molecule obtained from cochlear tissue by polymerase chain reaction. The nucleotide sequence of a clone, named cochlear G(12)alpha, had 99.2% identity to mouse macrophage G(12)alpha. Using an antibody which is selective for G(12)alpha, expression of the cochlear G(12)alpha was localized in outer and inner hair cells of the organ of Corti. Possible functional roles of this G protein in hair cells are discussed. C1 NIDOCD,NEUROCHEM LAB,BETHESDA,MD 20892. AICHI PREFECTURAL COLONY,INST DEV RES,DEPT BIOCHEM,AICHI,JAPAN. RP TACHIBANA, M (reprint author), NIDOCD,MOLEC BIOL LAB,BLDG 36,ROOM 5D-08,BETHESDA,MD 20892, USA. NR 19 TC 13 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD FEB PY 1994 VL 21 IS 3-4 BP 355 EP 358 DI 10.1016/0169-328X(94)90267-4 PG 4 WC Neurosciences SC Neurosciences & Neurology GA MV342 UT WOS:A1994MV34200019 PM 8170357 ER PT J AU KAISER, SM SEBAG, M RHIM, JS KREMER, R GOLTZMAN, D AF KAISER, SM SEBAG, M RHIM, JS KREMER, R GOLTZMAN, D TI ANTISENSE-MEDIATED INHIBITION OF PARATHYROID HORMONE-RELATED PEPTIDE PRODUCTION IN A KERATINOCYTE CELL-LINE IMPEDES DIFFERENTIATION SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID MESSENGER-RNA; HUMORAL HYPERCALCEMIA; ADENYLATE-CYCLASE; SYNTHETIC PEPTIDE; BONE-RESORPTION; EPIDERMAL-CELLS; GROWTH-FACTOR; HUMAN-TUMOR; PROTEIN; EXPRESSION AB We have used antisense RNA technology to inhibit endogenous PTH-related peptide (PTHRP) production in an established human keratinocyte cell line, HPK1A, to assess the role of PTHRP as a modulator of cell differentiation. Initially to determine the specificity of any alterations in cell function that might be observed, HPK1A cells and Rat-5 fibroblasts (which do not synthesize PTHRP) were both infected with the same retrovirus (pYN) containing antisense PTHRP. In contrast. to antisense-infected HPK1A cells (HPK1A-AS), which show accelerated growth indices when endogenous PTHRP production is blocked, antisense-infected Rat-2 cells (Rat-2-AS) displayed no increase in cell proliferation. Consequently, this alteration in HPK1A cell function appeared to be specific to the inhibition of PTHRP production. In HPK1A-AS cells, no PTHRP transcript was observed in cytoplasmic RNA, and none was sequestered in a nuclear RNA preparation. Therefore, hybridization with the antisense strand appears to destabilize PTHRP mRNA, leading to rapid disappearance of the sense-antisense heteroduplex. We then examined the effect of PTHRP inhibition on keratinocyte differentiation using three indices. PTHRP inhibition in HPK1A-AS cells resulted in reduced high mol wt keratin production, as assessed by immunocytochemistry. Expression of mRNA encoding transglutaminase and involucrin was decreased in HPK1A-AS cells compared to that in control cells under conditions of high ambient calcium. Involucrin protein levels were also diminished in HPK1A-AS cells in parallel with the reduced levels of involucrin gene expression. These data, therefore, show that interference with PTHRP production inhibits expression of maturation-specific keratinocyte indices and indicate that endogenous PTHRP acts to enhance differentiation in this keratinocyte model. C1 ROYAL VICTORIA HOSP, CALCIUM RES LAB, MONTREAL H3A 1A1, PQ, CANADA. MCGILL UNIV, DEPT MED, CALCIUM RES LAB, MONTREAL H3A 1A1, PQ, CANADA. MCGILL UNIV, DEPT PHYSIOL, MONTREAL H3A 1A1, PQ, CANADA. NCI, BETHESDA, MD 20892 USA. NR 53 TC 93 Z9 93 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD FEB PY 1994 VL 8 IS 2 BP 139 EP 147 DI 10.1210/me.8.2.139 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MX286 UT WOS:A1994MX28600002 PM 8170470 ER PT J AU MORRISON, A SUGINO, A AF MORRISON, A SUGINO, A TI THE 3'-]5' EXONUCLEASES OF BOTH DNA-POLYMERASES DELTA AND EPSILON PARTICIPATE IN CORRECTING ERRORS OF DNA-REPLICATION IN SACCHAROMYCES-CEREVISIAE SO MOLECULAR & GENERAL GENETICS LA English DT Article DE DNA POLYMERASES EPSILON AND DELTA; 3'-]5' EXONUCLEASE; REPLICATION ERRORS; SPONTANEOUS MUTATIONS; SACCHAROMYCES CEREVISIAE ID YEAST CHROMOSOME-III; ESCHERICHIA-COLI; SEQUENCE; FIDELITY; SUBUNIT; ALPHA; GENE AB DNA polymerases II (epsilon) and III (delta) are the only nuclear DNA polymerases known to possess an intrinsic 3'-->5' exonuclease in Saccharomyces cerevisiae. We have investigated the spontaneous mutator phenotypes of DNA polymerase delta and epsilon 3'-->5' exonuclease-deficient mutants, pol3-01 and pol2-4, respectively. pol3-01 and pol2-4 increased spontaneous mutation rates by factors of the order of 10(2) and 10(1), respectively, measured as URA3 forward mutation and his7-2 reversion. Surprisingly, a double mutant pol2-4 pol3-01 haploid was inviable. This was probably due to accumulation of unedited errors, since a pol2-4/pol2-4 pol3-01/pol3-01 diploid was viable, with the spontaneous his7-2 reversion rate increased by about 2 x 10(3)-fold. Analysis of mutation rates of double mutants indicated that the 3'-->5' exonucleases of DNA polymerases delta and epsilon can act competitively and that, like the 3'-->5' exonuclease of DNA polymerase delta, the 3'-->5' exonuclease of DNA polymerase epsilon acts in series with the PMS1 mismatch correction system. Mutational spectra at a URA3 gene placed in both orientations near to a defined replication origin provided evidence that the 3'-->5' exonucleases of DNA polymerases delta and epsilon act on opposite DNA strands, but were in sufficient to distinguish conclusively between different models of DNA replication. C1 OSAKA UNIV,MICROBIAL DIS RES INST,DEPT MOLEC IMMUNOL,SUITA,OSAKA 565,JAPAN. NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. NR 25 TC 165 Z9 167 U1 0 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0026-8925 J9 MOL GEN GENET JI Mol. Gen. Genet. PD FEB PY 1994 VL 242 IS 3 BP 289 EP 296 DI 10.1007/BF00280418 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA MY292 UT WOS:A1994MY29200007 PM 8107676 ER PT J AU PADLAN, EA AF PADLAN, EA TI ANATOMY OF THE ANTIBODY MOLECULE SO MOLECULAR IMMUNOLOGY LA English DT Review DE X-RAY STRUCTURES; ANTIBODY-LIGAND INTERACTIONS; POLYREACTIVITY; HUMANIZATION STRATEGIES ID BENCE-JONES PROTEIN; LIGHT-CHAIN DIMER; 2 CRYSTAL FORMS; COMPLEMENTARITY-DETERMINING REGIONS; POLYREACTIVE NATURAL ANTIBODIES; INFLUENZA-VIRUS NEURAMINIDASE; IMMUNOGLOBULIN FAB FRAGMENT; RESHAPING HUMAN-ANTIBODIES; HUMAN MONOCLONAL-ANTIBODY; 3-DIMENSIONAL STRUCTURE AB The structures of the various regions of an antibody molecule are analysed and correlated with biological function. The structural features which relate to potential applications are detailed. RP PADLAN, EA (reprint author), NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 178 TC 642 Z9 653 U1 12 U2 82 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 FEB PY 1994 VL 31 IS 3 BP 169 EP 217 DI 10.1016/0161-5890(94)90001-9 PG 49 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA MY340 UT WOS:A1994MY34000001 PM 8114766 ER PT J AU BROWN, P MCRAE, A MORGAN, OC RODGERSJOHNSON, P AF BROWN, P MCRAE, A MORGAN, OC RODGERSJOHNSON, P TI PROCEEDINGS OF THE SYMPOSIUM TRANSMISSIBLE-AND-NONTRANSMISSIBLE-NEURODEGENERATIVE-DISORDERS HELD IN OCHO-RIOS, JAMAICA, FEBRUARY, 28-MARCH 3, 1993 SO MOLECULAR NEUROBIOLOGY LA English DT Editorial Material C1 GOTHENBURG UNIV,INST ANAT & CELL BIOL,GOTHENBURG,SWEDEN. UNIV W INDIES,DEPT MED,MONA,JAMAICA. UNIV W INDIES,DEPT MED,KINGSTON,JAMAICA. RP BROWN, P (reprint author), NIH,CNS STUDIES LAB,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0893-7648 J9 MOL NEUROBIOL JI Mol. Neurobiol. PD FEB PY 1994 VL 8 IS 1 BP R9 EP R9 DI 10.1007/BF02778002 PG 1 WC Neurosciences SC Neurosciences & Neurology GA NJ233 UT WOS:A1994NJ23300001 ER PT J AU MASOOD, K WU, CP BRAUNEIS, U WEIGHT, FF AF MASOOD, K WU, CP BRAUNEIS, U WEIGHT, FF TI DIFFERENTIAL ETHANOL SENSITIVITY OF RECOMBINANT N-METHYL-D-ASPARTATE RECEPTOR SUBUNITS SO MOLECULAR PHARMACOLOGY LA English DT Article ID LONG-TERM POTENTIATION; CENTRAL-NERVOUS-SYSTEM; NMDA RECEPTOR; ACETYLCHOLINE-RECEPTOR; HIPPOCAMPAL-NEURONS; CLONED CDNAS; CLONING; EXPRESSION; RAT; NEUROTOXICITY AB The recombinant N-methyl-D-aspartate (NMDA) receptor subunit zeta 1 and the heteromeric subunit combinations epsilon 1/zeta 1, epsilon 2/zeta 1, and epsilon 3/zeta 1 were expressed in Xenopus oocytes and their sensitivities to ethanol were investigated using the two-electrode voltage-clamp technique. NMDA-activated currents in oocytes expressing subunit combinations epsilon 1/zeta 1 or epsilon 2/zeta 1 were significantly inhibited by 50 mM ethanol, whereas NMDA-activated currents associated with the homomeric expression of zeta 1 or the heteromeric epsilon 3/zeta 1 combination were not significantly affected by 50 mM ethanol. Ethanol decreased the maximal amplitude (E(max)) of the concentration-response curve for NMDA-activated current, without significantly affecting the EC(50). The values of percentage inhibition by ethanol were not significantly different, regardless of the amplitude of current activated by NMDA concentrations from 10 to 250 mu M. Different NMDA receptor subunits and subunit combinations exhibited differences in the concentration-response curves for ethanol. NMDA-activated current associated with the epsilon 1/zeta 1 subunit combination was increasingly inhibited by increasing concentrations of ethanol from 25 to 100 mM, whereas 25 mM ethanol elicited nearly maximal inhibition of NMDA-activated current associated with the epsilon 2/zeta 1 subunits, i.e., the inhibition by 50 or 100 mM ethanol was not significantly different. NMDA-activated current associated with the epsilon 3/zeta 1 subunit combination, on the other hand, was significantly inhibited only by 100 mM ethanol, and NMDA-activated current associated with the homomeric zeta 1 subunit was not significantly affected by ethanol concentrations of less than or equal to 100 mM. Because NMDA receptor subunits are differentially distributed throughout the brain, the observations suggest that the differential sensitivity of NMDA receptor subunits to ethanol may contribute to the differences in ethanol sensitivity observed in different types of neurons. RP MASOOD, K (reprint author), NIAAA, MOLEC & CELLULAR LAB, 12501 WASHINGTON AVE, ROCKVILLE, MD 20852 USA. NR 35 TC 161 Z9 164 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 FEB PY 1994 VL 45 IS 2 BP 324 EP 329 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MY862 UT WOS:A1994MY86200022 PM 8114679 ER PT J AU RELLING, MV NEMEC, J SCHUETZ, EG SCHUETZ, JD GONZALEZ, FJ KORZEKWA, KR AF RELLING, MV NEMEC, J SCHUETZ, EG SCHUETZ, JD GONZALEZ, FJ KORZEKWA, KR TI O-DEMETHYLATION OF EPIPODOPHYLLOTOXINS IS CATALYZED BY HUMAN CYTOCHROME-P450 3A4 SO MOLECULAR PHARMACOLOGY LA English DT Article ID HUMAN-LIVER CYTOCHROME-P-450; EXPRESSED HUMAN CYTOCHROME-P450S; PHASE-I TRIAL; MULTIDRUG RESISTANCE; ETOPOSIDE VP-16-213; SYSTEMIC EXPOSURE; DRUG-INTERACTIONS; VACCINIA VIRUS; TENIPOSIDE; CDNA AB We previously demonstrated that O-demethylation of the pendant dimethoxyphenol ring of epipodophyllotoxins to produce their respective catechol metabolites is catalyzed by cytochrome(s) P450 in human liver microsomes. Our objective was to identify the specific human cytochrome(s) P450 responsible for catechol formation. Using a panel of prototypical substrates and inhibitors for specific cytochromes P450, we identified substrates for CYP3A4 (midazolam, erythromycin, cyclosporin, and dexamethasone) as inhibitors of catechol formation from both etoposide and teniposide. Dexamethasone inhibition was competitive, with K-i values of 60 and 45 mu M for etoposide and teniposide, respectively. In 58 human livers, the correlation coefficients for teniposide catechol formation versus 1'- and 4-hydroxymidazolam formation were 80% and 85%, respectively; for etoposide catechol formation versus 1'- and 4-hydroxymidazolam formation r(2) was 83% and 79%, respectively. Teniposide and etoposide catechol formation rates were also significantly correlated with immunodetectable CYP3A (r(2) = 49% and 51%, respectively) and not with immunodetectable CYP1A2, 2E1, or 2C8. Finally, cDNAs for human CYP3A4, 3A5, 2A6, 2B6, 2C8, and 2C9 were functionally expressed in HepG2 cells, using a vaccinia viral vector. Teniposide and etoposide catechol formation was catalyzed primarily by 3A4 (15.4 and 40.9 pmol/ pmol/hr, respectively) and to a lesser degree by 3A5 (1.94 and 11.3 pmol/pmol/hr, respectively), whereas there was no detectable O-demethylation of epipodophyllotoxins by 2A6, 2B6, 2C8, 2C9, or the control virus alone. Moreover, the relative activities of midazolam hydroxylation, compared with O-demethylation of epipodophyllotoxins, were similar for heterologously expressed 3A4 and for human liver microsomes. We conclude that catechol formation from teniposide and etoposide is primarily mediated by human CYP3A4, making these reactions susceptible to inhibition by prototypical 3A substrates and inhibitors. C1 UNIV TENNESSEE, DEPT CLIN PHARM, CTR PEDIAT PHARMACOKINET & THERAPEUT, MEMPHIS, TN 38163 USA. NCI, FREDERICK CANC RES & DEV CTR, PRI DYNCORP, CHEM SYNTH & ANAL LAB, FREDERICK, MD 21701 USA. NCI, MOLEC CARCINOGENESIS LAB, BETHESDA, MD 20892 USA. RP RELLING, MV (reprint author), ST JUDE CHILDRENS RES HOSP, DEPT PHARMACEUT, 332 N LAUDERDALE, MEMPHIS, TN 38105 USA. FU NCI NIH HHS [N01-CO-74102, CA21765, R29 CA51001] NR 46 TC 158 Z9 161 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD FEB PY 1994 VL 45 IS 2 BP 352 EP 358 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MY862 UT WOS:A1994MY86200026 PM 8114683 ER PT J AU ALTSCHUL, SF BOGUSKI, MS GISH, W WOOTTON, JC AF ALTSCHUL, SF BOGUSKI, MS GISH, W WOOTTON, JC TI ISSUES IN SEARCHING MOLECULAR SEQUENCE DATABASES SO NATURE GENETICS LA English DT Review ID AMINO-ACID SEQUENCES; PATTERN-RECOGNITION; PROTEIN SEQUENCES; STATISTICAL SIGNIFICANCE; SMITH-WATERMAN; SCORING MATRIX; REPETITIVE DNA; GENERAL-METHOD; ALIGNMENTS; IDENTIFICATION AB Sequence similarity search programs are versatile tools for the molecular biologist, frequently able to identify possible DNA coding regions and to provide clues to gene and protein structure and function. While much attention had been paid to the precise algorithms these programs employ and to their relative speeds, there is a constellation of associated issues that are equally important to realize the full potential of these methods. Here, we consider a number of these issues, including the choice of scoring systems, the statistical significance of alignments, the masking of uninformative or potentially confounding sequence regions, the nature and extent of sequence redundancy in the databases and network access to similarity search services. C1 NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. RI Gish, Warren/C-8123-2012 NR 93 TC 582 Z9 591 U1 0 U2 20 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 FEB PY 1994 VL 6 IS 2 BP 119 EP 129 DI 10.1038/ng0294-119 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA MU763 UT WOS:A1994MU76300005 PM 8162065 ER PT J AU MCDONALD, MT PAPENBERG, KA GHOSH, S GLATFELTER, AA BIESECKER, BB HELMBOLD, EA MARKEL, DS ZOLOTOR, A MCKINNON, WC VANDERSTOEP, JL JACKSON, CE IANNUZZI, M COLLINS, FS BOEHNKE, M PORTEOUS, ME GUTTMACHER, AE MARCHUK, DA AF MCDONALD, MT PAPENBERG, KA GHOSH, S GLATFELTER, AA BIESECKER, BB HELMBOLD, EA MARKEL, DS ZOLOTOR, A MCKINNON, WC VANDERSTOEP, JL JACKSON, CE IANNUZZI, M COLLINS, FS BOEHNKE, M PORTEOUS, ME GUTTMACHER, AE MARCHUK, DA TI A DISEASE LOCUS FOR HEREDITARY HEMORRHAGIC TELANGIECTASIA MAPS TO CHROMOSOME 9Q33-34 SO NATURE GENETICS LA English DT Article ID HEMORRHAGIC TELANGIECTASIA; IDENTIFICATION; POLYMORPHISMS; EXPRESSION; LINKAGE; 9Q32-34; FAMILY; CHAIN; DNA AB Hereditary haemorrhagic telangiectasia (HHT), or Osler-Weber-Rendu disease, is an autosomal dominant vascular dysplasia of unknown pathogenesis reading to 'widespread' dermal, mucosal and visceral telangiectases and recurrent haemorrhage. We have mapped the HHT gene, by linkage analysis, to markers on 9q33-34 in two large multi-generation families. Haplotype analysis and mapping of recombination breakpoints gives a 4 cM interval between D9S61 and D9S63 as the most likely location of the gene. The closest marker, D9S65, is estimated to be within 1 cM of the gene and shows a combined lod score of 11.41. Two potential candidate genes, COL5A1 and ZNF79, are also located within 9q33-34. These results provide a starting point for the eventual cloning of the HHT gene. C1 UNIV MICHIGAN,DEPT HUMAN GENET,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT PEDIAT & COMMUNICABLE DIS,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT BIOSTAT,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT RADIAT ONCOL,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT INTERNAL MED,ANN ARBOR,MI 48109. UNIV MICHIGAN,CTR HUMAN GENOME,ANN ARBOR,MI 48109. UNIV VERMONT,COLL MED,DEPT PEDIAT,BURLINGTON,VT 05405. HENRY FORD HOSP,DIV CLIN & MOLEC GENET,DETROIT,MI 48202. HENRY FORD HOSP,DIV PULM MED,DETROIT,MI 48202. NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. UNIV NEWCASTLE UPON TYNE,DEPT HUMAN GENET,NEWCASTLE TYNE NE2 4AA,TYNE & WEAR,ENGLAND. WESTERN GEN HOSP,CLIN GENET SERV,EDINBURGH EH4 2XY,MIDLOTHIAN,SCOTLAND. DUKE UNIV,MED CTR,DEPT GENET,DURHAM,NC 27710. FU NHLBI NIH HHS [HL49171] NR 31 TC 122 Z9 126 U1 0 U2 7 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 FEB PY 1994 VL 6 IS 2 BP 197 EP 204 DI 10.1038/ng0294-197 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA MU763 UT WOS:A1994MU76300017 PM 8162075 ER PT J AU DERSCH, CM AKUNNE, HC PARTILLA, JS CHAR, GU DECOSTA, BR RICE, KC CARROLL, FI ROTHMAN, RB AF DERSCH, CM AKUNNE, HC PARTILLA, JS CHAR, GU DECOSTA, BR RICE, KC CARROLL, FI ROTHMAN, RB TI STUDIES OF THE BIOGENIC-AMINE TRANSPORTERS .1. DOPAMINE REUPTAKE BLOCKERS INHIBIT [H-3] MAZINDOL BINDING TO THE DOPAMINE TRANSPORTER BY A COMPETITIVE MECHANISM - PRELIMINARY EVIDENCE FOR DIFFERENT BINDING DOMAINS SO NEUROCHEMICAL RESEARCH LA English DT Article DE COCAINE; MAZINDOL; DOPAMINE TRANSPORTER; BTCP ID GUINEA-PIG BRAIN; H-3 GBR-12935 BINDING; HIGH-AFFINITY BINDING; UPTAKE SITES; COCAINE BINDING; UPTAKE COMPLEX; NONHUMAN-PRIMATES; LIGAND-BINDING; RAT-BRAIN; GBR-12935 BINDING AB The present study addressed the hypothesis that the DA transporter ligand, [H-3]mazindol, labels multiple sites/states associated with the dopamine (DA) transporter in striatal membranes. Incubations with [H-3]mazindol proceeded for 18-24 hr at 4 degrees C in 55.2 mM sodium phosphate buffer, pH 7.4, with a protease inhibitor cocktail. In order to obtain data suitable for quantitative curve fitting, it was necessary to repurify the [H-3]mazindol by HPLC before a series of experiments. Under these conditions, we observed greater than 80% specific binding. The method of binding surface analysis was used to characterize the interaction of GBR12935, BTCP, mazindol, and CFT with binding site/sites labeled by [H-3]mazindol. A one site model fit the data as well as the two site model: Bmax = 16911 fmol/mg protein, Kd of [H-3]mazindol = 75 nM, Ki of GBR12935 = 8.1 nM, Ki of CFT = 50 nM and Ki of BTCP = 44 nM. The inhibitory mechanism (competitive or noncompetitive) of several drugs (GBR12935, CFT, BTCP, cocaine, cis-flupentixol, nomifensine, WIN35,065-2, bupropion, PCP, and benztropine) was determined. All drugs inhibited [H-3]mazindol binding by a competitive mechanism. Although the ligand-selectivity of the [H-3]mazindol binding site indicates that it is the uptake inhibitor recognition site of the classic DA transporter, the quantitative differences among the ligand-selectivities of different radioligands for the same site suggest that each radioligand labels different overlapping domains of the DA uptake inhibitor recognition site. It is likely that development of domain-selective drugs may further our understanding of the DA transporter. C1 NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD 21224. NIDDK,MED CHEM LAB,BETHESDA,MD 20892. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NR 52 TC 31 Z9 31 U1 1 U2 3 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD FEB PY 1994 VL 19 IS 2 BP 201 EP 208 DI 10.1007/BF00966817 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA MQ728 UT WOS:A1994MQ72800015 PM 8183430 ER PT J AU DALAKAS, MC AF DALAKAS, MC TI HIGH-DOSE INTRAVENOUS IMMUNOGLOBULIN AND SERUM VISCOSITY - RISK OF PRECIPITATING THROMBOEMBOLIC EVENTS SO NEUROLOGY LA English DT Article ID IMMUNE GLOBULIN; MONOCLONAL GAMMOPATHY; THERAPY; POLYMYOSITIS; NEUROPATHY AB High-dose intravenous immunoglobulin (Mg) can increase blood viscosity in vitro and has been associated with cardiovascular or cerebrovascular thromboembolism. Because thromboembolic events were observed in two (3%) of 65 patients we treated with Mg, we measured serum viscosity serially in 13 patients (five with amyotrophic lateral sclerosis [ALS], eight with IgM paraproteinemic polyneuropathy) before and immediately after each of three consecutive monthly infusions of Mg. We correlated changes in viscosity with serial determinations of the total serum IgG, IgM, and IgA before and after each infusion. Serum viscosity increased after Mg in all the patients by 0.1 to 1.0 centipoise (cp) (mean, 0.55 cp). In three ALS patients and in all the patients with paraproteinemic polyneuropathy, serum viscosity exceeded the upper limit of normal (normal, 1.5 to 1.9 cp) and increased as high as 2.6 cp. The increase in viscosity occurred immediately after completion of the infusion, declined over 1 month, and appeared to correlate best with the serum IgG level, which after the infusions was as high as 6,160 mg/dl (normal, 545 to 1,560 mg/dl). I conclude that Mg increases serum viscosity and in many patients can cross the symptomatic threshold level. Because increased serum viscosity can impair blood flow and trigger a cardiovascular or cerebrovascular thromboembolic event, Mg should be used judiciously and with concurrent monitoring of serum viscosity in elderly patients and patients with cryoglobulinemia, monoclonal gammopathies, high lipoproteins, or preexisting vascular disease. RP DALAKAS, MC (reprint author), NINCDS,MED NEUROL BRANCH,NEUROMUSCULAR DIS SECT,BLDG 10,ROOM 4N248,BETHESDA,MD 20892, USA. NR 29 TC 214 Z9 214 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 FEB PY 1994 VL 44 IS 2 BP 223 EP 226 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA MW890 UT WOS:A1994MW89000005 PM 8309562 ER PT J AU BALDERESCHI, M AMATO, MP NENCINI, P PRACUCCI, G LIPPI, A AMADUCCI, L GAUTHIER, S BEATTY, L QUIROGA, P KLASSEN, G GALEA, A MUSCAT, P OSUNTOKUN, B OGUNNIYI, A PORTERASANCHEZ, A BERMEJO, F HENDRIE, H BURDINE, V BRASHEAR, A FARLOW, M MAGGI, S KATZMAN, R AF BALDERESCHI, M AMATO, MP NENCINI, P PRACUCCI, G LIPPI, A AMADUCCI, L GAUTHIER, S BEATTY, L QUIROGA, P KLASSEN, G GALEA, A MUSCAT, P OSUNTOKUN, B OGUNNIYI, A PORTERASANCHEZ, A BERMEJO, F HENDRIE, H BURDINE, V BRASHEAR, A FARLOW, M MAGGI, S KATZMAN, R TI CROSS-NATIONAL INTERRATER AGREEMENT ON THE CLINICAL DIAGNOSTIC-CRITERIA FOR DEMENTIA SO NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; MENTAL-DISORDERS; PSYCHIATRIC-DIAGNOSIS; POPULATION SURVEY; RELIABILITY AB We assessed the interobserver agreement on the clinical diagnosis of dementia syndrome and dementia subtypes as part of a cross-national project on the prevalence of dementia. Fourteen clinicians from the participating countries (Canada, Chile, Malta, Nigeria, Spain, and the United States) independently assessed the diagnosis of 51 patients whose clinical information was in standard records written in English. We used the DSM-III-R and ICD-10 criteria for dementia syndrome, the NINCDS-ADRDA criteria for Alzheimer's disease (AD), and the ICD-10 criteria for other dementing diseases, and measured interobserver agreement. We found comparable levels of agreement on the diagnosis of dementia using the DSM-III-R (kappa = 0.67) as well as the ICD-10 criteria (kappa = 0.69). Cognitive impairment without dementia was a major source of disagreement (kappa = 0.10). The kappa values were 0.58 for probable AD, 0.12 for possible AD, and rose to 0.72 when the two categories were merged. The interrater reproducibility of the diagnosis of vascular dementia was 0.66 in terms of kappa index; the diagnoses of other dementing disorders as a whole reached a kappa value of 0.40. This study suggests that clinicians from different cultures and medical traditions can use the DSM-III-R and the ICD-10 criteria for dementia effectively and thus reliably identify dementia cases in cross-national research. The interrater agreement on the diagnosis of dementia might be improved if clear-cut guidelines in the definition of cognitive impairment are provided. To improve the reliability of AD diagnosis in epidemiologic studies, we suggest that the NINCDS-ADRDA ''probable'' and ''possible'' categories be merged. C1 UNIV FLORENCE,DEPT NEUROL,FLORENCE,ITALY. MONTREAL GEN HOSP,MONTREAL,PQ,CANADA. DEPT NEUROPSIQUIATRIA,CONCEPCION,CHILE. INT INST AGING,VALLETTA,MALTA. NEUROL UNIT,IBADAN,NIGERIA. HOSP 12 OCTUBRE,MADRID,SPAIN. INDIANA UNIV,DEPT PSYCHIAT,INDIANAPOLIS,IN. INDIANA UNIV,DEPT NEUROL,INDIANAPOLIS,IN. NIA,WHO,BETHESDA,MD. UNIV CALIF SAN DIEGO,DEPT NEUROSCI,LA JOLLA,CA 92093. RP BALDERESCHI, M (reprint author), CTR SMID,VIA CAIROLI 8-A,I-50131 FLORENCE,ITALY. NR 17 TC 75 Z9 80 U1 2 U2 5 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB PY 1994 VL 44 IS 2 BP 239 EP 242 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA MW890 UT WOS:A1994MW89000008 PM 8309565 ER PT J AU PATNEAU, DK WRIGHT, PW WINTERS, C MAYER, ML GALLO, V AF PATNEAU, DK WRIGHT, PW WINTERS, C MAYER, ML GALLO, V TI GLIAL-CELLS OF THE OLIGODENDROCYTE LINEAGE EXPRESS BOTH KAINATE-PREFERRING AND AMPA-PREFERRING SUBTYPES OF GLUTAMATE-RECEPTOR SO NEURON LA English DT Article ID RAT CEREBELLAR CULTURES; EXCITATORY AMINO-ACIDS; QUISQUALATE RECEPTORS; HIPPOCAMPAL-NEURONS; MOLECULAR-CLONING; MACROGLIAL CELLS; PROGENITOR-CELL; NERVOUS-SYSTEM; HIGH-AFFINITY; CHANNELS AB mRNAs for AMPA- and kainate-preferring glutamate receptor subunits are expressed abundantly in the CNS, yet functional studies of neurons and glia from brain suggest selective expression of AMPA receptors. We now show that glial cells of the O-2A lineage express rapidly desensitizing responses to kainate, mRNAs for GluR6, GluR7, KA-1, and KA-2, rapidly desensitizing responses to AMPA, and mRNAs for CluR-B, -C, and -D. Analysis of glutamate receptor currents in single cells reveals two receptor populations with high and low affinity for kainate and different sensitivity for potentiation by concanavalin A and for block of desensitization by cyclothiazide. Our experiments describe the characterization of native kainate-preferring receptors in glia and reveal coexpression in single cells of functional AMPA- and kainate-preferring receptors. RP PATNEAU, DK (reprint author), NICHHD,CELLULAR & MOLEC NEUROPHYSIOL LAB,BETHESDA,MD 20892, USA. RI Mayer, Mark/H-5500-2013 NR 51 TC 264 Z9 265 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD FEB PY 1994 VL 12 IS 2 BP 357 EP 371 DI 10.1016/0896-6273(94)90277-1 PG 15 WC Neurosciences SC Neurosciences & Neurology GA MY500 UT WOS:A1994MY50000011 PM 7509160 ER PT J AU SAVORY, J HERMAN, MM ERASMUS, RT BOYD, JC WILLS, MR AF SAVORY, J HERMAN, MM ERASMUS, RT BOYD, JC WILLS, MR TI PARTIAL REVERSAL OF ALUMINUM-INDUCED NEUROFIBRILLARY DEGENERATION BY DESFERRIOXAMINE IN ADULT MALE RABBITS SO NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY LA English DT Article DE ALUMINUM MALTOLATE; DESFERRIOXAMINE; NEURODEGENERATION; NEUROFILAMENTS ID ALZHEIMERS-DISEASE; NEUROFILAMENT ANTIGENS; TANGLES; PATHOLOGY; IRON AB Desferrioxamine, a chelating agent with a high affinity for aluminium, has been reported to slow the clinical progression of dementia associated with Alzheimer's disease [4]. We report here the effects of desferrioxamine treatment on aluminium-induced neurofibrillary degeneration in rabbits. Adult male New Zealand white rabbits received a single injection of aluminium-maltolate into the lateral cerebral ventricle. Three days later, one group of rabbits was treated with intramuscular injections of desferrioxamine twice daily: a second group received saline instead of desferrioxamine. Both groups were sacrificed 4 or 5 days following initiation of desferrioxamine or saline treatment. Minimal neurofibrillary degeneration was found in two of six desferrioxamine-treated rabbits, while all six rabbits treated with saline showed extensive neurofibrillary degeneration, particularly in the ventral horn of the lower spinal cord. Quantitation of the neurofibrillary degeneration in ventral horn neurons of lumbar cord revealed 30% to be affected in saline-treated animals compared to zero-affected neurons following desferrioxamine treatment. When sacrificed just 3 days after aluminium treatment, 50% of the rabbits already revealed neurofibrillary degeneration, corresponding to the timepoint when desferrioxamine treatment was begun in the above animals; on quantitation, 7.5% of ventral lumbar cord neurons were involved. These findings indicate a partial reversal of aluminium-induced neurodegeneration by desferrioxamine. Delaying desferrioxamine treatment to 6 days after aluminium administration prevented any reversal of the aluminium effect; all animals had abundant neurofibrillary degeneration as well as a striking basophillic spicular deposit of calcium and argyrophilic material in the leptomeninges, lateral ventricles and brain parenchyma adjacent to these areas. Pre-treatment of rabbits with desferrioxamine did not provide the expected protective effect against aluminium-induced neurofibrillary degeneration. No pathological effects were observed when saline or desferrioxamine were given alone, without aluminium. C1 UNIV VIRGINIA,HLTH SCI CTR,DEPT INTERNAL MED,CHARLOTTESVILLE,VA 22908. NIMH,NEUROSCI CTR ST ELIZABETH,CLIN BRAIN DISORDERS BRANCH,NEUROPATHOL SECT,WASHINGTON,DC. RP SAVORY, J (reprint author), UNIV VIRGINIA,HLTH SCI CTR,DEPT PATHOL & BIOCHEM,BOX 168,CHARLOTTESVILLE,VA 22908, USA. NR 23 TC 22 Z9 23 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0305-1846 J9 NEUROPATH APPL NEURO JI Neuropathol. Appl. Neurobiol. PD FEB PY 1994 VL 20 IS 1 BP 31 EP 37 DI 10.1111/j.1365-2990.1994.tb00954.x PG 7 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA MY818 UT WOS:A1994MY81800004 PM 8208339 ER PT J AU BREIER, A BUCHANAN, RW WALTRIP, RW LISTWAK, S HOLMES, C GOLDSTEIN, DS AF BREIER, A BUCHANAN, RW WALTRIP, RW LISTWAK, S HOLMES, C GOLDSTEIN, DS TI THE EFFECT OF CLOZAPINE ON PLASMA NOREPINEPHRINE - RELATIONSHIP TO CLINICAL EFFICACY SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE CLOZAPINE; PLASMA NOREPINEPHRINE; SCHIZOPHRENIA; CLINICAL EFFICACY; ALPHA(1)-RECEPTOR, MECHANISM OF ACTION; CATECHOLAMINES ID CEREBROSPINAL-FLUID NOREPINEPHRINE; SCHIZOPHRENIC-PATIENTS; ANTIPSYCHOTIC-DRUGS; CSF NOREPINEPHRINE; DOPAMINE; BRAIN; CATECHOLAMINES; NORADRENALINE; METABOLITES; MECHANISMS AB Clozapine is an atypical neuroleptic medication with superior efficacy to conventional antipsychotic agents for patients with chronic, symptomatic schizophrenia. Neurochemical characteristics that distinguish clozapine from other neuroleptics and contribute to its differential efficacy are not known. We assessed the effects of clozapine on plasma levels of norepinephrine (NE) in a double-blind, parallel groups comparison of clozapine (n = 11) and haloperidol (n = 15) in chronic schizophrenic outpatients who had been previously treated with fluphenazine. Simultaneous measurements were obtained for plasma levels of the catecholamine precursor dopa, the dopamine metabolite dihydroxyphenylacetic acid (DOPAC), the NE metabolite 3,4-dihydroxyphenylglycol (DHPG), adrenocorticotropin (ACTH), cortisol, and hemodynamic parameters. Clozapine produced marked increases (471%) in plasma NE levels, whereas haloperidol had no significant effects on plasma NE levels. Clozapine also increased dopa and tended to increase DOPAC levels, without effects on DHPG, ACTH, or cortisol levels and without consistent changes in blood pressure. Across patients, the magnitude of clozapine-induced increments in plasma NE levels was positively related to improvement in positive symptoms and global symptomatology and was unrelated to the occurrence of extrapyramidal symptoms. The results suggest that clozapine differs importantly from other neuroleptics in increasing plasma NE levels, with the peripheral noradrenergic stimulation related to its superior efficacy profile. The unchanged DHPG levels and absence of hypertension suggest a more complex mechanism of action of clozapine than heightened NE release alone. C1 MARYLAND PSYCHIAT RES CTR,BALTIMORE,MD. NIMH,CLIN PSYCHOBIOL BRANCH,BETHESDA,MD 20892. NINCDS,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. RP BREIER, A (reprint author), NIMH,EXPTL THERAPEUT BRANCH,9000 ROCKVILLE PIKE,BLDG 10 ROOM 4N212,BETHESDA,MD 20892, USA. NR 50 TC 81 Z9 82 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD FEB PY 1994 VL 10 IS 1 BP 1 EP 7 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA MY494 UT WOS:A1994MY49400002 PM 8179790 ER PT J AU GOYER, PF COHEN, RM ANDREASON, PJ SEMPLE, WE CLAYTON, AH KING, AC COMPTONTOTH, BA SCHULZ, SC AF GOYER, PF COHEN, RM ANDREASON, PJ SEMPLE, WE CLAYTON, AH KING, AC COMPTONTOTH, BA SCHULZ, SC TI POSITRON-EMISSION TOMOGRAPHY AND PERSONALITY-DISORDERS SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE POSITRON-EMISSION TOMOGRAPHY; CEREBRAL GLUCOSE METABOLISM; PERSONALITY DISORDER; BORDERLINE PERSONALITY DISORDER; ANTISOCIAL PERSONALITY DISORDER; REGIONAL CEREBRAL METABOLIC RATE OF GLUCOSE ID OBSESSIVE-COMPULSIVE DISORDER; CEREBRAL GLUCOSE-METABOLISM; CEREBROSPINAL-FLUID; PREFRONTAL SUBSTRATE; SUSTAINED ATTENTION; AMINE METABOLITES; CHILDHOOD-ONSET; CSF 5-HIAA; SCHIZOPHRENIA; RATES AB This study used positron-emission tomography to examine cerebral metabolic rates of glucose (CMRG) in 17 patients with DSM III-R diagnoses of personality disorder. Within the group of 17 personality disorder patients, there was a significant inverse correlation between a life history of aggressive impulse difficulties and regional CMRG in the frontal cortex of the transaxial plane approximately 40 mm above the canthomeatal line (CML) (r = - .56, p = 0.17). Diagnostic groups included antisocial (n = 6), borderline (n = 6), dependent (n = 2), and narcissistic (n = 3). Regional CMRG in the six antisocial patients and in the six borderline patients was compared to a control group of 43 subjects using an analysis of covariance with age and sex as covariates. In the borderline personality disorder group, there was a significant decrease in frontal cortex metabolism in the transaxial plane approximately 81 mm above the CML and a significant increase in the transaxial plane approximately 53 mm above the CML (F[1,45] = 8.65, p = .005; and F[1,45] = 7.68, p = .008, respectively). C1 CASE WESTERN RESERVE UNIV,SCH MED,DEPT PSYCHIAT,DIV NEUROPSYCHIAT IMAGING,CLEVELAND,OH 44106. NIMH,CLIN BRAIN IMAGING SECT,BETHESDA,MD. UNIV VIRGINIA,SCH MED,DEPT BEHAV MED & PSYCHIAT,CHARLOTTESVILLE,VA 22908. RP GOYER, PF (reprint author), UNIV HOSP CLEVELAND,DEPT PSYCHIAT,DIV NEUROPSYCHIAT IMAGING,2040 ABINGTON RD,CLEVELAND,OH 44106, USA. NR 34 TC 168 Z9 170 U1 2 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD FEB PY 1994 VL 10 IS 1 BP 21 EP 28 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA MY494 UT WOS:A1994MY49400004 PM 8179791 ER PT J AU MICHELS, KM HEEMSKERK, FMJ SAAVEDRA, JM AF MICHELS, KM HEEMSKERK, FMJ SAAVEDRA, JM TI SELECTIVE CHANGES IN ANGIOTENSIN-II AT(1) AND AT(2) RECEPTOR SUBTYPES IN THE RAT SUPERIOR COLLICULUS FOLLOWING EYE ENUCLEATION SO NEUROSCIENCE LA English DT Article ID SUPERFICIAL GRAY LAYER; BINDING-SITES; RETINAL AFFERENTS; SUBSTANCE-P; GUINEA-PIG; BRAIN; DEAFFERENTATION; PROJECTION; NUCLEUS; ORGANIZATION AB In the brain of young (two weeks old) rats, angiotensin II receptors (AT(2) receptors) are found in brain nuclei which receive and integrate direct visual input from the retina, the suprachiasmatic nuclei (containing only AT(1) receptors), the lateral geniculate nuclei (containing AT(2) receptors) and the superior colliculus (which contains both receptor types with a majority of AT(2)). In adult rats, angiotensin II receptors are present in the suprachiasmatic nuclei and the superior colliculus but not in the lateral geniculate, Using quantitative autoradiography we found that, in adult rats, bilateral eye enucleation caused a significant decrease in AT(2) receptor binding, but not in AT(1) receptor binding, and only in the superior colliculus. Unilateral enucleation of 12-day-old pups led to a decrease in AT(2) receptor binding from the contralateral superior colliculus, as early as day 2 postenucleation. Conversely, there was a significant increase in binding to AT(1) receptors in the ipsilateral superior colliculus after seven days. No changes were seen in the lateral geniculate or suprachiasmatic nuclei. Angiotensin II binding to subcellular fractions of tissue from the superior colliculus region of 19-day-old pups suggested that AT(2) receptor sites were present on the plasma membrane of the postsynaptic cell body. Membrane binding studies also showed a significant decrease in AT(2) receptor binding to the same subcellular fractions when 19-day-old pups, enucleated seven days earlier, were compared to sham-operated animals. Our results suggest that expression of AT(1) and AT(2) receptors in the superior colliculus may be regulated by retinal input. C1 NIMH,CLIN SCI LAB,PHARMACOL SECT,BETHESDA,MD 20892. NR 54 TC 14 Z9 14 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD FEB PY 1994 VL 58 IS 4 BP 835 EP 844 DI 10.1016/0306-4522(94)90460-X PG 10 WC Neurosciences SC Neurosciences & Neurology GA MY417 UT WOS:A1994MY41700014 PM 8190260 ER PT J AU DE LUCA, LM DARWICHE, N CELLI, G KOSA, K JONES, C ROSS, S CHEN, LC AF DE LUCA, LM DARWICHE, N CELLI, G KOSA, K JONES, C ROSS, S CHEN, LC TI VITAMIN-A IN EPITHELIAL DIFFERENTIATION AND SKIN CARCINOGENESIS SO NUTRITION REVIEWS LA English DT Article; Proceedings Paper CT 15th Marabou Symposium on Vitamin A: From Molecular Biology to Public Health CY JUN 11, 1993 CL STOCKHOLM, SWEDEN SP MARABOU FDN PROMOT NUTR RES ID ACUTE PROMYELOCYTIC LEUKEMIA; RETINOIC ACID RECEPTOR; T(15-17) TRANSLOCATION; SQUAMOUS METAPLASIA; CARCINOMA INSITU; TUMOR PROMOTION; RAR-ALPHA; HISTOGENESIS; INHIBITION; FUSES RP DE LUCA, LM (reprint author), NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, DIFFERENTIAT CONTROL SECT, BLDG 37, RM 3A-17, BETHESDA, MD 20892 USA. OI Darwiche, Nadine/0000-0002-1862-5426 NR 32 TC 19 Z9 19 U1 0 U2 0 PU INT LIFE SCIENCES INST NORTH AMERICA PI WASHINGTON PA ONE THOMAS CIRCLE, N W, 9TH FLOOR, WASHINGTON, DC 20005 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD FEB PY 1994 VL 52 IS 2 BP 45 EP 52 PN 2 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA NB729 UT WOS:A1994NB72900006 ER PT J AU NORUM, K JAMES, P ERIKSSON, U BLOMHOFF ROSS, C DELUCA, L DREVON, C BUSCH, C MADEN, M MANGELSDORF, D CHYTIL, F DETHE, H WALD, N DOLL, R WILLETT, WC GREENWALD, P BRUCE, A WOLF, G OLSON, JA RUSSELL, R ROSENBERG, I UNDERWOOD, B GOPALAN, C MARTORELL, R ONG, D LIE, S AF NORUM, K JAMES, P ERIKSSON, U BLOMHOFF ROSS, C DELUCA, L DREVON, C BUSCH, C MADEN, M MANGELSDORF, D CHYTIL, F DETHE, H WALD, N DOLL, R WILLETT, WC GREENWALD, P BRUCE, A WOLF, G OLSON, JA RUSSELL, R ROSENBERG, I UNDERWOOD, B GOPALAN, C MARTORELL, R ONG, D LIE, S TI UNTITLED - DISCUSSION SO NUTRITION REVIEWS LA English DT Discussion ID BETA-CAROTENE; VITAMIN-A; RETINOL ACYLTRANSFERASE; LECITHIN; ACID C1 ROWETT RES INST,BUCKSBURN AB2 9SB,ABERDEEN,SCOTLAND. KAROLINSKA INST,LUDWIG INST CANC RES,S-10401 STOCKHOLM,SWEDEN. MED COLL PENN,DEPT BIOCHEM,DIV NUTR,PHILADELPHIA,PA 19129. NCI,DIFFERENTIAT CONTROL SECT,BETHESDA,MD 20892. UNIV OSLO,INST NUTR RES,DIETARY RES SECT,N-0317 OSLO,NORWAY. UNIV UPPSALA HOSP,DEPT PATHOL,S-75185 UPPSALA,SWEDEN. UNIV LONDON KINGS COLL,RANDALL INST,DEV BIOL RES CTR,LONDON WC2B 5RL,ENGLAND. UNIV TEXAS,SW MED CTR,HOWARD HUGHES MED INST,RES LAB,DALLAS,TX 75235. VANDERBILT UNIV,SCH MED,DEPT BIOCHEM,NASHVILLE,TN 37232. HOP ST LOUIS,NATL CTR SCI RES,F-75475 PARIS 10,FRANCE. UNIV LONDON ST BARTHOLOMEWS HOSP & MED COLL,DEPT ENVIRONM & PREVENT MED,LONDON EC1M 6BQ,ENGLAND. RADCLIFFE INFIRM,CLIN TRIAL SERV UNIT,OXFORD OX2 6HE,OXON,ENGLAND. RADCLIFFE INFIRM,IMPERIAL CANC RES FUND,CANC STUDIES UNIT,OXFORD OX2 6HE,ENGLAND. HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,BOSTON,MA 02115. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. NATL FOOD ADM TOXICOL LAB,S-75126 UPPSALA,SWEDEN. UNIV CALIF BERKELEY,DEPT NUTR SCI,BERKELEY,CA 94720. IOWA STATE UNIV SCI & TECHNOL,DEPT BIOCHEM & BIOPHYS,VITAMIN RES GRP A,AMES,IA 50011. TUFTS UNIV,USDA,HUMAN NUTR RES CTR,BOSTON,MA 02111. WHO,NUTR UNIT,CH-1211 GENEVA,SWITZERLAND. NUTR FDN INDIA,NEW DELHI 110049,INDIA. CORNELL UNIV,DIV NUTR SCI,ITHACA,NY 14853. NATL HOSP NORWAY,DEPT PEDIAT,N-0027 OSLO,NORWAY. RP NORUM, K (reprint author), UNIV OSLO,INST NUTR RES,POSTBOKS 1046,N-0316 OSLO 3,NORWAY. RI Martorell, Reynaldo /I-2539-2012 NR 17 TC 0 Z9 0 U1 1 U2 1 PU INT LIFE SCIENCES INST NORTH AMERICA PI WASHINGTON PA ONE THOMAS CIRCLE, N W, 9TH FLOOR, WASHINGTON, DC 20005 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD FEB PY 1994 VL 52 IS 2 BP 74 EP 86 PN 2 PG 13 WC Nutrition & Dietetics SC Nutrition & Dietetics GA NB729 UT WOS:A1994NB72900010 ER PT J AU TOLAYMAT, A SANCHEZRAMOS, L YERGEY, AL VIEIRA, NE ABRAMS, SA EDELSTEIN, P AF TOLAYMAT, A SANCHEZRAMOS, L YERGEY, AL VIEIRA, NE ABRAMS, SA EDELSTEIN, P TI PATHOPHYSIOLOGY OF HYPOCALCIURIA IN PREECLAMPSIA - MEASUREMENT OF INTESTINAL CALCIUM-ABSORPTION SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID INTRACELLULAR FREE CALCIUM; PARATHYROID-HORMONE; NORMAL-PREGNANCY; METABOLISM; SERUM; 1,25-DIHYDROXYVITAMIN-D; HYPERCALCIURIA; EXCRETION AB Objective: To analyze calcium absorption using stable isotopes in patients with preeclampsia and in normotensive controls. Methods: Fifteen pregnant subjects were studied: eight with preeclampsia (hypertension and proteinuria) and seven normotensive controls. All patients were ingesting their normal diet. The subjects received two stable calcium isotopic tracers. An oral tracer (Ca-44, 0.0124 mmol/kg) was given with milk, while an intravenous tracer (Ca-42, 0.00249 mmol/kg) was infused over 7-10 minutes. Calcium concentration was determined by atomic absorption spectrophotometry, and isotope ratios by thermal ionization mass spectrometry from pooled 24-hour urine samples. Results: No difference was noted in fractional intestinal absorption between preeclamptic subjects (0.282 +/- 0.051) and normotensive controls (0.306 +/- 0.079) (P = .49). However, the fraction of dietary calcium appearing in the urine differed significantly (0.06 for preeclamptic subjects and 0.087 for normotensive controls; P = .008). Conclusions: Despite the indirect evidence of others, calcium absorption does not appear to be impaired in patients with preeclampsia. The retention site of the unexcreted calcium is unidentified. C1 UNIV FLORIDA,HLTH SCI CTR JACKSONVILLE,DEPT OBSTET & GYNECOL,JACKSONVILLE,FL 32209. NICHHD,METAB ANAL & MASS SPECTROMETRY SECT,BETHESDA,MD. BAYLOR COLL MED,USDA ARS,CHILDRENS NUTR RES CTR,HOUSTON,TX. MATERN HOSP NUESTRA SENORA ALTAGRACIA,SANTO DOMINGO,DOMINICAN REP. RP TOLAYMAT, A (reprint author), UNIV FLORIDA,HLTH SCI CTR JACKSONVILLE,DEPT PEDIAT,653-1 W 8TH ST,JACKSONVILLE,FL 32209, USA. OI Abrams, Steven/0000-0003-4972-9233 NR 25 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 1994 VL 83 IS 2 BP 239 EP 243 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA MT964 UT WOS:A1994MT96400014 PM 8290187 ER PT J AU DOSEMECI, M MCLAUGHLIN, JK CHEN, JQ HEARL, F MCCAWLEY, M WU, Z CHEN, RG PENG, KL CHEN, AL REXING, SH BLOT, WJ AF DOSEMECI, M MCLAUGHLIN, JK CHEN, JQ HEARL, F MCCAWLEY, M WU, Z CHEN, RG PENG, KL CHEN, AL REXING, SH BLOT, WJ TI INDIRECT VALIDATION OF A RETROSPECTIVE METHOD OF EXPOSURE ASSESSMENT USED IN A NESTED CASE-CONTROL STUDY OF LUNG-CANCER AND SILICA EXPOSURE SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID REPORTED WORK HISTORY; OCCUPATIONAL EXPOSURE; VALIDITY; QUESTIONNAIRE; INFORMATION; INTERVIEW; AGREEMENT AB Validations of retrospective methods of assessment used in occupational epidemiological studies have rarely been published. This study is an indirect validation of a quantitative retrospective assessment of exposure to silica used in a nested case-control study of lung cancer among workers at 29 metal mines and pottery factories in China. Indices of cumulative total dust and cumulative respirable dust were calculated by merging work histories with the historical exposure profile for each subject. To validate indirectly the methods of exposure assessment used in the study of lung cancer, trends for exposure response relation between the two indices of exposure to silica and risk of silicosis were evaluated with 376 patients with silicosis from the study population as the cases, and 1262 controls without silicosis for comparison. Age adjusted odds ratios (ORs) as a measure of risk of silicosis showed striking trends with both indices of exposure to silica. For cumulative respirable dust, the OR (95% confidence interval) rose from 7.6 (5.1-11.4) for low exposure to 20.0 (13.2-30.6) for medium exposure, and to 51.7 (31.0-86.8) for high exposure. The strength of the association between exposure to silica and risk of silicosis suggests that the retrospective assessment of exposure used in the case-control study of lung cancer would accurately reflect an exposure response relation between silica and lung cancer, if it existed. C1 TONGJI MED UNIV,DEPT LABOR HLTH & OCCUPAT DIS,WUHAN,PEOPLES R CHINA. NIOSH,MORGANTOWN,WV 26505. RP DOSEMECI, M (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,6130 EXECUT BLVD,ROOM 418,ROCKVILLE,MD 20852, USA. NR 32 TC 18 Z9 20 U1 1 U2 4 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD FEB PY 1994 VL 51 IS 2 BP 136 EP 138 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NE457 UT WOS:A1994NE45700010 PM 8111462 ER PT J AU MAVROTHALASSITIS, G FISHER, RJ SMYTH, F WATSON, DK PAPAS, TS AF MAVROTHALASSITIS, G FISHER, RJ SMYTH, F WATSON, DK PAPAS, TS TI STRUCTURAL INFERENCES OF THE ETS1 DNA-BINDING DOMAIN DETERMINED BY MUTATIONAL ANALYSIS SO ONCOGENE LA English DT Article ID GENE FAMILY; C-FOS; TRANSCRIPTION FACTORS; ONCOGENIC ACTIVITY; PROTEIN; C-ETS-1; CELLS; MOTIF; PROTOONCOGENE; SEQUENCE AB The ets family of transcription factors is characterized by a conserved region that harbors the DNA-binding activity. We performed extensive deletion and mutational analyses, as well as DNA-peptide interaction studies necessary to identify the determinants of the DNA-binding activity of the ETS1 oncoprotein. We found that amino acids beyond the 85 amino acid conserved region are required in order to afford maximum DNA-binding activity in a heterologous system. Mutation throughout the binding domain can have a detrimental effect on binding activity, indicating that proper folding of the entire domain is necessary for DNA binding. A peptide, as small as 37 residues (K37N), derived from the basic region of the ETS1 binding domain, is sufficient to exhibit sequence-specific DNA recognition. Total randomization of Lysine 379, Lysine 381 and Arginine 391 within this region fails to provide functional substitutions, indicating that these specific amino acids within the basic region are required for binding. Transactivation activity of the ETS1 proteins bearing mutations was consistent with their DNA-binding activity, indicating that the primary (if not only) function of this domain is to provide sequence-specific DNA recognition activity. Our mutational analysis, as well as modeling predictions, lead us to propose a helix-turn-helix structure for the basic region of the ETS1 binding domain that is able to interact directly with DNA. We also propose that the hydrophobic alpha-helical region, surrounding tryptophan 338, is fundamental for proper protein folding and;functioning of the ets binding domain. C1 PROGRAM RESOURCES INC,DYNCORP,FREDERICK,MD 21701. RP MAVROTHALASSITIS, G (reprint author), NCI,MOLEC ONCOL LAB,POB B,FREDERICK,MD 21702, USA. RI Fisher, Robert/B-1431-2009 NR 35 TC 19 Z9 19 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB PY 1994 VL 9 IS 2 BP 425 EP 435 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA MW248 UT WOS:A1994MW24800009 PM 8290254 ER PT J AU MERLO, GR VENESIO, T TAVERNA, D MARTE, BM CALLAHAN, R HYNES, NE AF MERLO, GR VENESIO, T TAVERNA, D MARTE, BM CALLAHAN, R HYNES, NE TI GROWTH SUPPRESSION OF NORMAL MAMMARY EPITHELIAL-CELLS BY WILD-TYPE P53 SO ONCOGENE LA English DT Article ID HUMAN BREAST-CANCER; CELLULAR TUMOR-ANTIGEN; BETA-CASEIN GENE; MUTANT P53; EMBRYO FIBROBLASTS; SV40 DNA; MUTATIONS; PROTEIN; TRANSFORMATION; EXPRESSION AB p53 mutations are frequent in human breast cancer. In order to understand the role of p53 in the context of the accumulation of mutations in breast cancer, a model of non transformed mammary cells was sought. The HC11 cells are immortalized, non transformed rodent mammary epithelial cells which synthesize milk proteins following stimulation with lactogenic hormones. p53 protein was readily detected in HC11 protein extracts with the PAb421 antibody. Two mutations were identified in the p53 cDNA from HC11 cells: a missense mutation at codon 138, substituting Trp for Cys, and a microdeletion, codon 123 to 130, of exon 5. The latter results from an intronic mutation of the splice acceptor site at the intron 4/exon 5 junction. The mutations affect separate p53 alleles, and no wt allele was found. Wt p53 was introduced into HC11 cells by means of a retroviral vector, under the control of a Cd++-inducible promoter. In the presence of CdSO4 a dramatic growth inhibition was observed. A temperature-sensitive mutant p53 gene was also transfected into HC11 cells. This resulted in a marked inhibition of cells growth at 32 degrees C, when the p53 is in the wt conformation, while no effect was observed at 37 degrees C, when the mutant conformation is predominant. wt p53-mediated inhibition of monolayer growth does not involve induction of programmed cell death and does not activate de novo synthesis of differentiation-specific milk proteins. We conclude that mutations in the p53 gene likely played a role in their immortalization. The HC11 cells provide a model for assessing the cooperative action of other mutations in mammary tumorigenesis. C1 USL 1,S GIOVANNI HOSP,I-10123 TURIN,ITALY. NCI,ONCOGENET SECT,BETHESDA,MD 20892. RP MERLO, GR (reprint author), FRIEDRICH MIESCHER INST,POB 2543,CH-4002 BASEL,SWITZERLAND. RI taverna, daniela/J-8358-2016 OI taverna, daniela/0000-0002-6365-527X NR 65 TC 43 Z9 43 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB PY 1994 VL 9 IS 2 BP 443 EP 453 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA MW248 UT WOS:A1994MW24800011 PM 8290256 ER PT J AU XU, NZ MCCORMICK, F GUTKIND, JS AF XU, NZ MCCORMICK, F GUTKIND, JS TI THE NONCATALYTIC DOMAIN OF RAS-GAP INHIBITS TRANSFORMATION-INDUCED BY G-PROTEIN COUPLED RECEPTORS SO ONCOGENE LA English DT Article ID GTPASE-ACTIVATING PROTEIN; TYROSINE PHOSPHORYLATION; OVEREXPRESSION; CELLS; DNA AB We have studied the relationship between vas-GAP and G protein coupled receptors in a proliferative setting comprised of NIH3T3 expressing transfected muscarinic receptors (mAChRs). GAP expression plasmids were engineered to encode wild-type GAP, its carboxyl-terminal catalytic domain, a mutant lacking a portion of the catalytic domain, and an amino-terminal domain which contained the hydrophobic region as well as SH2-SH3 domains. Cotransfection of each GAP expression plasmid into NIH3T3 cells did not affect the transforming ability of the v-mos oncogene, but plasmids encoding wild-type GAP or the mutant consisting of an intact catalytic domain inhibited transformation induced by normal c-ras. Wild-type GAP also prevented transformation by mi mAChRs, whereas the mutant consisting of only its catalytic domain lacked any demonstrable effect. In contrast, the N-terminal non-catalytic domain of GAP effectively prevented m1-induced focus-formation. Cell lines coexpressing m1 receptors and each of the GAP constructs revealed that GAP proteins do not affect mi receptor density, receptor ligand binding characteristics or coupling to the PI-PLC signal transduction pathway. Thus, our findings suggest a role for the N-terminal non-catalytic domain of GAP in regulating biological functions mediated by G protein-coupled receptors. C1 NIDR,CELLULAR DEV & ONCOL LAB,MOLEC SIGNALING UNIT,BETHESDA,MD 20892. ONYX PHARMACEUT,RICHMOND,CA 94806. RI Gutkind, J. Silvio/A-1053-2009 NR 23 TC 14 Z9 14 U1 1 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB PY 1994 VL 9 IS 2 BP 597 EP 601 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA MW248 UT WOS:A1994MW24800027 PM 8290270 ER PT J AU EDELHOFF, S AYER, DE ZERVOS, AS STEINGRIMSSON, E JENKINS, NA COPELAND, NG EISENMAN, RN BRENT, R DISTECHE, CM AF EDELHOFF, S AYER, DE ZERVOS, AS STEINGRIMSSON, E JENKINS, NA COPELAND, NG EISENMAN, RN BRENT, R DISTECHE, CM TI MAPPING OF 2 GENES ENCODING MEMBERS OF A DISTINCT SUBFAMILY OF MAX INTERACTING PROTEINS - MAD TO HUMAN-CHROMOSOME-2 AND MOUSE CHROMOSOME-6, AND MXI1 TO HUMAN-CHROMOSOME-10 AND MOUSE CHROMOSOME-19 SO ONCOGENE LA English DT Note ID INSITU HYBRIDIZATION; DNA-SEQUENCES; LEUKEMIA; MYC; BINDING AB Both the MAD and the MXI1 genes encode basic-helix-loop-helix-leucine zipper (bHLH-Zip) transcription factors which bind Max in vitro, forming a sequence-specific DNA-binding complex similar to the Myc-Max heterodimer. Mad and Myc compete for binding to Max. In addition, Mad has been shown to act as a transcriptional repressor while Myc appears to function as an activator. Mxi1 also appears to lack a transcriptional activation domain. Therefore, Mxi1 and Mad might antagonize Myc function and are candidate tumor suppressor genes. We report here the mapping of the MAD and MXI1 genes in human and mouse by fluorescence in situ hybridization (FISH) and by recombination mapping. The MAD gene was mapped to human chromosome 2 at band p13 by FISH and to mouse chromosome 6 by meiotic mapping. The MXI1 gene was mapped to human chromosome 10 at band q25 and on mouse chromosome 19 at region D by FISH. There was a second site of hybridization on mouse chromosome 2 at region C, which may represent a pseudogene or a related sequence. The mapping results confirm regions of conservation between human chromosome 2p13 and mouse chromosome 6 and between chromosome 10q25 and mouse chromosome 19D. Human chromosomes 2p13 and 10q25 have been involved in specific tumors where the role of Mad and Mxi1 can now he investigated. C1 UNIV WASHINGTON,DEPT PATHOL,SEATTLE,WA 98195. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL,BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 26 TC 111 Z9 111 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB PY 1994 VL 9 IS 2 BP 665 EP 668 PG 4 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA MW248 UT WOS:A1994MW24800036 PM 8290278 ER PT J AU PRASAD, DDK RAO, VN LEE, L REDDY, ESP AF PRASAD, DDK RAO, VN LEE, L REDDY, ESP TI DIFFERENTIALLY SPLICED ERG-3 PRODUCT FUNCTIONS AS A TRANSCRIPTIONAL ACTIVATOR SO ONCOGENE LA English DT Note ID ETS-RELATED PROTEIN; PUTATIVE ONCOGENE SPI-1; MURINE LEUKEMIA-VIRUS; LONG TERMINAL REPEAT; DNA-BINDING DOMAIN; C-ETS-1 PROTOONCOGENE; C-FOS; GENE FAMILY; FLI-1 GENE; V-ETS AB ets oncogene superfamily consists of a family of transcriptional factors that functions as activators and/or repressors. Previously, we have identified a member of this ets superfamily namely erg, ets related gene. erg gene was shown to code for at least two proteins erg-1 and erg-2 because of alternative splicing and alternative usage of initiation codon. In this report we show that erg gene codes for an additional erg variant protein, erg-3 as a result of differential splicing which results in the insertion of 24 amino acids in the coding region of erg-2 protein. RNAase protection analysis revealed that erg-3 transcripts are expressed in a variety of cells. Erg-3 was also found to activate the transcription of the reporter TK-CAT gene linked to er g target sequences suggesting that erg3 codes for a sequence specific transcriptional activator. C1 JEFFERSON CANC INST,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19107. NCI,FCRDC,PROGRAM RESOURCES INC,FREDERICK,MD 21702. FU NCI NIH HHS [CA 51083, CA 57157] NR 53 TC 25 Z9 26 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB PY 1994 VL 9 IS 2 BP 669 EP 673 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA MW248 UT WOS:A1994MW24800037 PM 8290279 ER PT J AU BOUZAS, EA CARUSO, RC DREWSBANKIEWICZ, MA KAISERKUPFER, MI AF BOUZAS, EA CARUSO, RC DREWSBANKIEWICZ, MA KAISERKUPFER, MI TI EVOKED-POTENTIAL ANALYSIS OF VISUAL PATHWAYS IN HUMAN ALBINISM SO OPHTHALMOLOGY LA English DT Article ID SYSTEM ANOMALIES; PROJECTIONS; FIELD; CATS; VEP AB Purpose: To explore the abnormal crossing of the retinogeniculate pathways in human albinos with visual-evoked potentials (VEPs). Methods: The authors studied the symmetry of the topographic distribution of pattern onset/offset VEPs over the posterior part of the scalp elicited by monocular stimulation of each eye in 31 consecutive patients with different types of albinism. Results: Twenty-one patients had asymmetric responses, with the major amplitude recorded over the lateral part of the scalp contralaterally to the stimulated eye in 14 patients and ipsilaterally in 7 patients. In two patients, the responses had a symmetric topographic distribution. In eight patients, the amplitude was so low that studying the symmetry was not possible. Conclusions: These findings demonstrate a non-uniform pattern of asymmetry as a result of the miswiring of the visual pathways in human albinism. Moreover, the tow amplitude of the VEP recorded in a consecutive series of patients shows the difficulty of the study of this phenomenon in a clinical setting. C1 NEI,OPHTHALM GENET & CLIN SERV BRANCH,BETHESDA,MD 20892. NR 39 TC 20 Z9 21 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD FEB PY 1994 VL 101 IS 2 BP 309 EP 314 PG 6 WC Ophthalmology SC Ophthalmology GA MX333 UT WOS:A1994MX33300021 PM 8115151 ER PT J AU ALLEN, G AF ALLEN, G TI DID REFLEXIVE CATALYSTS DRIVE CHEMICAL EVOLUTION SO ORIGINS OF LIFE AND EVOLUTION OF THE BIOSPHERE LA English DT Article ID ORIGINS; LIFE AB High-energy starting materials and energy sources on the primitive earth would have generated abundant and varied organic molecules of small or medium size. It is questionable, however, whether ordinary chemical evolution could have produced information-carrying polymers. The end point might have been a fixed steady state if some form of autocatalysis had not intervened. Autocatalytic synthesis is possible for small molecules as illustrated by the formose reaction, in which glycolaldehyde condenses with formaldehyde to form sugars, and resulting tetroses may cleave into two molecules of glycolaldehyde. This and other 'reflexive catalysts', some functioning in molecular aggregates, may have energized chemical evolution and carried it to a level at which RNA or an RNA analog could replicate itself. C1 NIMH,BETHESDA,MD 20892. NR 24 TC 2 Z9 2 U1 1 U2 5 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0169-6149 J9 ORIGINS LIFE EVOL B JI Orig. Life Evol. Biosph. PD FEB PY 1994 VL 24 IS 1 BP 57 EP 61 DI 10.1007/BF01582039 PG 5 WC Biology SC Life Sciences & Biomedicine - Other Topics GA MV218 UT WOS:A1994MV21800005 PM 7510381 ER PT J AU CLARKE, CG DIAMOND, LS AF CLARKE, CG DIAMOND, LS TI PATHOGENICITY, VIRULENCE AND ENTAMOEBA-HISTOLYTICA SO PARASITOLOGY TODAY LA English DT Editorial Material ID STRAINS RP CLARKE, CG (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. OI Clark, C Graham/0000-0002-0521-0977 NR 11 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0169-4758 J9 PARASITOL TODAY JI Parasitol. Today PD FEB PY 1994 VL 10 IS 2 BP 46 EP 47 DI 10.1016/0169-4758(94)90389-1 PG 2 WC Parasitology SC Parasitology GA MV152 UT WOS:A1994MV15200003 PM 15275497 ER PT J AU BURNS, JC NEWBURGER, JW SUNDELL, R WYATT, LS FRENKEL, N AF BURNS, JC NEWBURGER, JW SUNDELL, R WYATT, LS FRENKEL, N TI SEROPREVALENCE OF HUMAN HERPESVIRUS-7 IN PATIENTS WITH KAWASAKI-DISEASE SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Letter DE KAWASAKI DISEASE; HUMAN HERPESVIRUS 7 C1 HARVARD UNIV,SCH MED,DEPT CARDIOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. RP BURNS, JC (reprint author), UCSD,SCH MED,DEPT PEDIAT,LA JOLLA,CA 92093, USA. RI Burns, Jane/J-6167-2015 NR 4 TC 4 Z9 4 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD FEB PY 1994 VL 13 IS 2 BP 168 EP 169 DI 10.1097/00006454-199402000-00028 PG 2 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA MW838 UT WOS:A1994MW83800028 PM 8190553 ER PT J AU SCHNAPER, HW AF SCHNAPER, HW TI IMMUNIZATION PRACTICES IN CHILDHOOD NEPHROTIC SYNDROME - A SURVEY OF NORTH-AMERICAN PEDIATRIC NEPHROLOGISTS SO PEDIATRIC NEPHROLOGY LA English DT Article DE NEPHROTIC SYNDROME; IMMUNIZATION AB The indications for immunizing children with minimal change nephrotic syndrome are a subject of some controversy, since it has been reported that immunization may not be effective or may serve as an immunogenic stimulus that precipitates an episode of relapse. To determine the current recommendations of practicing pediatric nephrologists, a questionnaire was sent to the members of the American Society of Pediatric Nephrology. Over half responded, and the results of the survey indicated that a consensus for approaching immunization does not exist. Further, little data are available to support any particular immunization practice. Several potential means to accumulate such data are outlined. RP SCHNAPER, HW (reprint author), NIH,BLDG 30,ROOM 407,BETHESDA,MD 20892, USA. NR 0 TC 11 Z9 13 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0931-041X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD FEB PY 1994 VL 8 IS 1 BP 4 EP 6 PG 3 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA MU921 UT WOS:A1994MU92100002 PM 8142223 ER PT J AU SCHNAPER, HW AF SCHNAPER, HW TI CALL FOR A REGISTRY OF COMPLICATIONS OF IMMUNIZATION IN NEPHROTIC CHILDREN SO PEDIATRIC NEPHROLOGY LA English DT Letter DE IMMUNIZATION COMPLICATIONS; NEPHROTIC CHILDREN RP SCHNAPER, HW (reprint author), NIH,BLDG 30,ROOM 414,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0931-041X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD FEB PY 1994 VL 8 IS 1 BP 132 EP 132 PG 1 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA MU921 UT WOS:A1994MU92100037 PM 8142217 ER PT J AU HAHN, SH BRANTLY, ML OLIVER, C ADAMSON, M KALER, SG GAHL, WA AF HAHN, SH BRANTLY, ML OLIVER, C ADAMSON, M KALER, SG GAHL, WA TI METALLOTHIONEIN SYNTHESIS AND DEGRADATION IN INDIAN CHILDHOOD CIRRHOSIS FIBROBLASTS SO PEDIATRIC RESEARCH LA English DT Article ID INHERITED COPPER TOXICOSIS; STORAGE DISEASE; IIA GENE; PROTEIN; LIVER; TRANSCRIPTION; BINDING; DOGS AB Indian childhood cirrhosis (ICC) is a fatal liver disease characterized by the accumulation of copper-sulfur aggregates. We demonstrated that cultured fibroblasts from a patient with ICC contain vesicular aggregates, fibrillar whorls, and crystalloids along with dilated rough endoplasmic reticulum filled with flocculent material. Although the copper content of the fibroblasts was normal, both basal and metal-induced metallothionein (MT) synthesis was reduced in the ICC cells. The lower MT synthesis in ICC cells was seen at copper concentrations of 100, 200, and 400 mu M, zinc concentrations of 50 and 100 mu M, and a cadmium concentration of 2 mu M. The lower MT synthesis in ICC cells was not due to failure of the cells to take up copper because Cu-67 uptake kinetics were normal is the mutant cells. MT degradation was also normal in the ICC cells. The size of human MT IIA mRNA was normal in the ICC cells, but its amount was reduced under both basal and metal-induced conditions. The MT IIA gene, which is the predominant MT gene in human beings, showed no sequence alterations in any of its exons, introns, or promoter region in the ICC cells compared with normal cells. These studies demonstrate that this case of ICC represents a genetic disease with some level of expression in cultured fibroblasts; the basic defect may involve insufficient MT mRNA and protein-synthesis for the copper load present. However, it remains to be determined whether reduced MT synthesis is a primary or secondary phenomenon. C1 NICHHD,HUMAN GENET BRANCH,HUMAN BIOCHEM GENET SECT,BETHESDA,MD 20892. NR 38 TC 18 Z9 19 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 FEB PY 1994 VL 35 IS 2 BP 197 EP 204 DI 10.1203/00006450-199402000-00015 PG 8 WC Pediatrics SC Pediatrics GA MU439 UT WOS:A1994MU43900012 PM 8165055 ER PT J AU SIMPSON, GA FOWLER, MG AF SIMPSON, GA FOWLER, MG TI GEOGRAPHIC-MOBILITY AND CHILDRENS EMOTIONAL/BEHAVIORAL ADJUSTMENT AND SCHOOL FUNCTIONING SO PEDIATRICS LA English DT Article DE GEOGRAPHIC MOBILITY; EMOTIONAL PROBLEMS; BEHAVIORAL PROBLEMS; SCHOOL PROBLEMS ID PSYCHOPATHOLOGY; ADOLESCENTS; FAMILIES AB Objective. To evaluate the relationship of geographic mobility to children's emotional/behavioral adjustment and school functioning. Design. Analysis of data from the 1988 National Health Interview Survey of Child Health in which multistage probability sampling was used to obtain data for nationally representative estimates of health and demographic characteristics of US children. Participants. 10 362 US school-age children and their families. Measurements. The 1988 National Health Interview Survey of Child Health includes data on health and demographic characteristics, emotional/behavioral variables, school functioning, and geographic mobility for 10 362 US school-age children. This study examined the relationship of children's geographic mobility to children's reported emotional problems, use of psychological help, scores on a Behavior Problem Index, repeating a grade in school, and being suspended or expelled from school. Results. Twenty-four percent of children have never moved, 35% of children have moved once or twice, and 39% of children aged 6 to 17 years have moved three or more times in their lifetime. Using multiple logistic regression to control for important demographic variables, children who moved three or more times were 2.3 times more likely to have had emotional/behavioral problems, 2.2 times more likely to have received psychological help, 1.7 times more likely to have repeated a grade, and 1.9 times more likely to have been suspended or expelled from school compared with children who had never moved. Multiple regression was also used to analyze the impact of mobility in relation to scores on the Behavior Problem Index. Children who moved three or more times were 1.6 times more likely to be in the top tenth percentile of scores on the Behavior Problem Index compared with children who had never moved. Conclusions. Children who move three or more times are at increased risk for emotional/behavioral and school problems. Thus, pediatricians, other health professionals, and educators should be alert to the potential educational and psychological problems among children from highly mobile families. C1 NIAID,BETHESDA,MD. RP SIMPSON, GA (reprint author), NATL CTR HLTH STAT,DIV HIS,ROOM 850,6525 BELCREST RD,HYATTSVILLE,MD 20782, USA. NR 28 TC 79 Z9 79 U1 1 U2 6 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD FEB PY 1994 VL 93 IS 2 BP 303 EP 309 PG 7 WC Pediatrics SC Pediatrics GA MU934 UT WOS:A1994MU93400030 PM 8121745 ER PT J AU HUSSON, RN MUELLER, BU FARLEY, M WOODS, L KOVACS, A GOLDSMITH, JC ONO, J LEWIS, LL BALIS, FM BROUWERS, P AVRAMIS, VI CHURCH, JA BUTLER, KM RASHEED, S JAROSINSKI, P VENZON, D PIZZO, PA AF HUSSON, RN MUELLER, BU FARLEY, M WOODS, L KOVACS, A GOLDSMITH, JC ONO, J LEWIS, LL BALIS, FM BROUWERS, P AVRAMIS, VI CHURCH, JA BUTLER, KM RASHEED, S JAROSINSKI, P VENZON, D PIZZO, PA TI ZIDOVUDINE AND DIDANOSINE COMBINATION THERAPY IN CHILDREN WITH HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION SO PEDIATRICS LA English DT Article DE HUMAN IMMUNODEFICIENCY VIRUS; ZIDOVUDINE; DIDANOSINE; NUCLEOSIDE ANALOGS; COMBINATION THERAPY; HIV THERAPY; ANTIRETROVIRAL THERAPY; PEDIATRIC HIV INFECTION ID AIDS-RELATED COMPLEX; PLACEBO-CONTROLLED TRIAL; PHASE-I TRIAL; 2',3'-DIDEOXYINOSINE DDI; CONTINUOUS-INFUSION; AZIDOTHYMIDINE AZT; ORAL ZIDOVUDINE; DOUBLE-BLIND; TOXICITY; HIV AB Objective. Zidovudine and didanosine are both beneficial for the treatment of human immunodeficiency virus (HIV) infection in children. Because disease progression and toxicity often limit their long-term use as single agents, new approaches to using nucleoside analogues are necessary to improve current antiretroviral therapy. Design. We conducted a phase I-II study to evaluate the tolerance, pharmacokinetics, and antiviral activity of the combination of zidovudine and didanosine in children with HIV infection. Sixty-eight children who were either previously untreated or who had manifested hematologic toxicity on full-dose zidovudine were enrolled. Eight dose combinations were studied in the previously untreated children, with doses of zidovudine ranging from 90 to 180 mg/m(2) every 6 hours and doses of didanosine ranging from 90 to 180 mg/m(2) every 12 hours. Results. Fifty-four previously untreated HIV-infected children were enrolled in this part of the study, of whom 49 remained in the study for a minimum of 24 weeks. For children with previous zidovudine-related hematologic toxicity, three dose levels with zidovudine at 60 mg/m(2) every 6 hours orally and didanosine ranging from 90 to 180 mg/m(2) every 12 hours orally were used. A total of 14 children were enrolled in this part of the study, and 12 remained on therapy for at least 24 weeks. No evidence of new or enhanced toxicity was observed in either group. After 24 weeks, the median CD4 cell count for all patients increased from 331 to 556 cells/mm(3) (P = .01). For the previously untreated group, the median increase in CD4 counts was from 386 to 726 cells/mm(3) (P = .003). The median p24 antigen concentration (in those with a detectable level at baseline) decreased from 95 to < 31 pg/mL (P < .001). The geometric mean titer of HIV in plasma decreased from 83.1 to 2.7 tissue culture infectious doses/mL (P = .001). Conclusions. The combination of zidovudine and didanosine was well-tolerated at doses as high as those used in single agent therapy. Potent in vivo antiviral activity was observed. Combination therapy with nucleoside analogues may be an important approach to optimizing the use of these agents in the treatment of HIV infection. C1 NCI, PEDIAT BRANCH, CLIN ONCOL PROGRAM, BETHESDA, MD 20892 USA. CHILDRENS HOSP LOS ANGELES, NEIL BOGART LABS, LOS ANGELES, CA USA. UNIV SO CALIF, LOS ANGELES CTY MED CTR, LOS ANGELES, CA 90033 USA. NCI, CLIN ONCOL PROGRAM, BIOSTAT & DATA MANAGEMENT SECT, BETHESDA, MD 20892 USA. RI Venzon, David/B-3078-2008 FU NCRR NIH HHS [MO1RR43] NR 28 TC 35 Z9 37 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD FEB PY 1994 VL 93 IS 2 BP 316 EP 322 PG 7 WC Pediatrics SC Pediatrics GA MU934 UT WOS:A1994MU93400032 PM 7907174 ER PT J AU SWEDO, SE LEONARD, HL KIESSLING, LS AF SWEDO, SE LEONARD, HL KIESSLING, LS TI SPECULATIONS ON ANTINEURONAL ANTIBODY-MEDIATED NEUROPSYCHIATRIC DISORDERS OF CHILDHOOD SO PEDIATRICS LA English DT Editorial Material ID OBSESSIVE-COMPULSIVE DISORDER; CHOREA; CHILDREN C1 BROWN UNIV, DEPT PEDIAT, PAWTUCKET, RI USA. MEM HOSP RHODE ISL, PAWTUCKET, RI USA. RP NIMH, CHILD PSYCHIAT BRANCH, BLDG 10, RM 6N240, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 29 TC 133 Z9 137 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD FEB PY 1994 VL 93 IS 2 BP 323 EP 326 PG 4 WC Pediatrics SC Pediatrics GA MU934 UT WOS:A1994MU93400033 PM 8121747 ER PT J AU WEDLUND, PJ KIMURA, S GONZALEZ, FJ NEBERT, DW AF WEDLUND, PJ KIMURA, S GONZALEZ, FJ NEBERT, DW TI I462V MUTATION IN THE HUMAN CYP1A1 GENE - LACK OF CORRELATION WITH EITHER THE MSP I 1.9 KB (M2) ALLELE OR CYP1A1 INDUCIBILITY IN A 3-GENERATION FAMILY OF EAST MEDITERRANEAN DESCENT SO PHARMACOGENETICS LA English DT Article ID ARYL-HYDROCARBON HYDROXYLASE; AH-RECEPTOR; LUNG-CANCER; CYTOCHROME-P450IA1 GENE; CDNA PROBE; DNA; POLYMORPHISM; LINKAGE; BINDING; IDENTIFICATION AB A 15-member three-generation family of Eastern Mediterranean descent was previously studied, and an association between CYP1A1 (cytochrome P(1)450, benzo[a]pyrene hydroxylase) inducibility and a CYP1A1 3'-polymorphism (the Msp I 1.9 kb allele) was reported (Petersen et al., Am J Hum Genet 1991: 48, 720-725). Here we have re-examined the original DNA (and in some cases, newly prepared DNA from freshly drawn blood) from these same individuals, in order to assess the association between CYP1A1 inducibility and both the CYP1A1 gene Msp I RFLP polymorphism and the CYP1A1 gene A --> G polymorphism at codon 462. This latter nucleotide change results in an altered amino acid (462Ile --> Val), which is purported to increase CYP1A1 enzyme activity and mutagenicity towards benzo[a]pyrene about two-fold among Japanese. Among the 15 members of this three-generation family examined, no absolute correlation was observed between the I462V genotype and either the Msp 11.9 kb allele or the CYP1A1 inducibility phenotype. We also found no absolute correlation between the Msp 11.9 kb allele and the CYP1A1 inducibility phenotype. C1 UNIV CINCINNATI,MED CTR,DEPT ENVIRONM HLTH,CINCINNATI,OH 45267. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. FU NIEHS NIH HHS [P30 ES06096] NR 29 TC 42 Z9 42 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 FEB PY 1994 VL 4 IS 1 BP 21 EP 26 DI 10.1097/00008571-199402000-00003 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA ND091 UT WOS:A1994ND09100003 PM 7516235 ER PT J AU RETTIE, AE WIENKERS, LC GONZALEZ, FJ TRAGER, WF KORZEKWA, KR AF RETTIE, AE WIENKERS, LC GONZALEZ, FJ TRAGER, WF KORZEKWA, KR TI IMPAIRED (S)-WARFARIN METABOLISM CATALYZED BY THE R144C ALLELIC VARIANT OF CYP2C9 SO PHARMACOGENETICS LA English DT Note ID MEPHENYTOIN HYDROXYLATION; VACCINIA VIRUS; AMINO-ACID; CYTOCHROME-P-450; CDNA; EXPRESSION; SUBFAMILY; TOLBUTAMIDE; SUBSTRATE; SEQUENCES C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RP RETTIE, AE (reprint author), UNIV WASHINGTON,DEPT MED CHEM,BAGLEY HALL BG-20,SEATTLE,WA 98195, USA. FU NIGMS NIH HHS [GM32165] NR 21 TC 366 Z9 382 U1 1 U2 5 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD FEB PY 1994 VL 4 IS 1 BP 39 EP 42 DI 10.1097/00008571-199402000-00005 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA ND091 UT WOS:A1994ND09100005 PM 8004131 ER PT J AU BICOUT, D BROSSEAU, C MARTINEZ, AS SCHMITT, JM AF BICOUT, D BROSSEAU, C MARTINEZ, AS SCHMITT, JM TI DEPOLARIZATION OF MULTIPLY SCATTERED WAVES BY SPHERICAL DIFFUSERS - INFLUENCE OF THE SIZE PARAMETER SO PHYSICAL REVIEW E LA English DT Note ID LIGHT; MEDIA AB We study numerically, using the Mie theory, light transmission through a multiply scattering medium composed of a collection of uncorrelated, optically inactive spherical particles. The characteristic length over which a plane-wave field is depolarized depends on whether it is initially linearly or circularly polarized and on the size of the particles. In a medium containing particles small compared to the wavelength (Rayleigh regime), the characteristic length of depolarization for incident linearly polarized light is found to exceed that for incident circularly polarized light, while the opposite is true in a medium composed of particles large compared to the wavelength (Mie regime). A comparison of numerical results with the data from measurements on suspensions of polystyrene latex spheres in water is made. Agreement between these simulations and experiment is good for the range of sizes considered in this paper. We also discuss the relevance of the helicity-flip model to the analysis of these data. C1 UNIV JOSEPH FOURIER,SPECT PHYS LAB,F-38042 ST MARTIN DHERES,FRANCE. CNRS,EXPERIMENTAT NUMER LAB,F-38042 GRENOBLE,FRANCE. NIH,NATL CTR RES RESOURCES,BETHESDA,MD 20892. RP BICOUT, D (reprint author), INST BIOL STRUCTURALE,41 AVE MARTYRS,F-38027 GRENOBLE 1,FRANCE. RI Martinez, Alexandre/B-4539-2008 OI Martinez, Alexandre/0000-0002-4395-0511 NR 17 TC 248 Z9 250 U1 1 U2 20 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1063-651X J9 PHYS REV E JI Phys. Rev. E PD FEB PY 1994 VL 49 IS 2 BP 1767 EP 1770 DI 10.1103/PhysRevE.49.1767 PG 4 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA NA921 UT WOS:A1994NA92100109 ER PT J AU MACLEAN, PD AF MACLEAN, PD TI HUMAN-NATURE - DUALITY OR TRIALITY SO POLITICS AND THE LIFE SCIENCES LA English DT Article C1 NIMH,BETHESDA,MD 20892. NR 14 TC 0 Z9 0 U1 0 U2 0 PU BEECH TREE PUBLISHING PI GUILDFORD PA 10 WATFORD CLOSE, GUILDFORD, SURREY, ENGLAND GU1 2EP SN 0730-9384 J9 POLIT LIFE SCI JI Polit. Life Sci. PD FEB PY 1994 VL 13 IS 1 BP 107 EP 112 PG 6 WC Biology; History & Philosophy Of Science; Social Issues SC Life Sciences & Biomedicine - Other Topics; History & Philosophy of Science; Social Issues GA NJ754 UT WOS:A1994NJ75400027 ER PT J AU CHEON, HG LAROCHELLE, WJ BOTTARO, DP BURGESS, WH AARONSON, SA AF CHEON, HG LAROCHELLE, WJ BOTTARO, DP BURGESS, WH AARONSON, SA TI HIGH-AFFINITY BINDING-SITES FOR RELATED FIBROBLAST GROWTH-FACTOR LIGANDS RESIDE WITHIN DIFFERENT RECEPTOR IMMUNOGLOBULIN-LIKE DOMAINS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PDGF-B; IGG; SPECIFICITY; HEPARIN; CELLS; LOCALIZATION; GENE AB Growth factors of the fibroblast growth factor (FGF) family bind receptors whose external domains are organized in a series of immunoglobulin-like loops. We engineered expression constructs in which cDNAs encoding individual immunoglobulin-like domains of the keratinocyte growth factor (KGF/FGF-7) receptor were fused to the mouse immunoglobulin heavy chain Fc domain (HFc). Each chimera was efficiently secreted from NIH 3T3 transfectants and migrated at the predicted molecular mass after SDS/PAGE. Scatchard analysis revealed that the chimera containing immunoglobulin-like domains 2 (D2) and 3 (D3) bound KGF and acidic FGF at high affinities comparable to the native receptor. However, individual immunoglobulin-like domain chimeras demonstrated marked specificity in their ligand interactions. D2-HFc bound acidic FGF at high affinity, whereas it did not detectably interact with KGF. Conversely, D3-HFc bound KGF at high affinity but exhibited no detectable interaction with acidic FGF. Their selective ligand binding properties were confirmed by the specific neutralization of acidic FGF or KGF mitogenic activity using D2 or D3 HFc, respectively. All of these findings established that the major binding sites for related FGF ligands are localized to distinct receptor immunoglobulin-like domains. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. AMER RED CROSS,JEROME H HOLLAND LAB BIOMED SCI,ROCKVILLE,MD 20855. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 27 TC 69 Z9 70 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 FEB 1 PY 1994 VL 91 IS 3 BP 989 EP 993 DI 10.1073/pnas.91.3.989 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MV278 UT WOS:A1994MV27800035 PM 8302878 ER PT J AU OSWALD, IP ELTOUM, I WYNN, TA SCHWARTZ, B CASPAR, P PAULIN, D SHER, A JAMES, SL AF OSWALD, IP ELTOUM, I WYNN, TA SCHWARTZ, B CASPAR, P PAULIN, D SHER, A JAMES, SL TI ENDOTHELIAL-CELLS ARE ACTIVATED BY CYTOKINE TREATMENT TO KILL AN INTRAVASCULAR PARASITE, SCHISTOSOMA-MANSONI, THROUGH THE PRODUCTION OF NITRIC-OXIDE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GROWTH-FACTOR; MACROPHAGES; INVITRO; GAMMA; MICE AB Like many pathogens that undergo an intravascular stage of development, larvae of the helminth parasite Schistosoma mansoni migrate through the blood vessels, where they are in close contact with endothelial cells. In vitro exposure of murine endothelial cells to various cytokines (interferon gamma, tumor necrosis factor alpha, and interleukin 1alpha or 1beta) resulted in their activation to kill schistosomula through an arginine-dependent mechanism involving production of nitric oxide (NO). Cytokine-treated endothelial cells showed increased expression of mRNA for the inducible form of the NO synthase, and both NO production and larval killing were suppressed by treatment with competitive inhibitors. The effector function of cytokine-treated endothelial cells was similar to that of activated inflammatory tissue macrophages, although activation appeared to be differentially regulated in these two cell types. Activated endothelial cells killed older (18-day) forms of the parasite, such as those currently thought to be a primary target of immune elimination in the lungs of mice previously vaccinated with radiation-attenuated cercariae, as well as newly transformed larvae. In C57BL/6 mice, which become resistant to S. mansoni infection as a result of vaccination with irradiated cercariae, endothelial cell morphology characteristic of activation was observed in the lung by 1-2 weeks after challenge infection. Similar endothelial cell changes were absent in P-strain mice, which do not become resistant as a result of vaccination. Together, these observations indicate that endothelial cells, not traditionally considered to be part of the immune system, may play an important role in immunity to S. mansoni and, by means of NO-dependent killing, could serve as effectors of resistance to other intravascular pathogens. C1 ECOLE NATL VET,DEPT GENET MOLEC,F-94704 MAISONS ALFORT,FRANCE. INST PASTEUR,BIOL MOLEC & DIFFERENTIAT,F-75754 PARIS,FRANCE. RP OSWALD, IP (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. RI Wynn, Thomas/C-2797-2011; OSWALD, Isabelle/A-8497-2013; OI OSWALD, Isabelle/0000-0001-9918-277X NR 26 TC 96 Z9 100 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 FEB 1 PY 1994 VL 91 IS 3 BP 999 EP 1003 DI 10.1073/pnas.91.3.999 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MV278 UT WOS:A1994MV27800037 PM 7508126 ER PT J AU ALARID, ET RUBIN, JS YOUNG, P CHEDID, M RON, D AARONSON, SA CUNHA, GR AF ALARID, ET RUBIN, JS YOUNG, P CHEDID, M RON, D AARONSON, SA CUNHA, GR TI KERATINOCYTE GROWTH-FACTOR FUNCTIONS IN EPITHELIAL INDUCTION DURING SEMINAL-VESICLE DEVELOPMENT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ANDROGEN; EPITHELIAL MESENCHYMAL INTERACTIONS; BRANCHING MORPHOGENESIS ID TISSUE RECOMBINANTS; RAT UTERUS; MESENCHYME; SECRETION; CYTODIFFERENTIATION; PURIFICATION; TESTOSTERONE; EXPRESSION; CELLS; DNA AB Development of the seminal vesicle (SV) is elicited by androgens and is dependent on epithelial-mesenchymal interactions. Androgenic signal transmission from the androgen-receptor-positive mesenchyme to the epithelium has been postulated to involve paracrine factors. Keratinocyte growth factor (KGF), a member of the fibroblast growth factor family, is produced by stromal/mesenchymal cells and acts specifically on epithelial cells. The KGF transcript was detected by reverse transcription-polymerase chain reaction in newborn mouse SVs and by Northern blot analysis of RNA from cultured neonatal SV mesenchymal cells. Newborn SVs placed in organ culture undergo androgen-dependent growth and differentiation. Addition of a KGF-neutralizing monoclonal antibody to this system caused striking inhibition of both SV growth and branching morphogenesis. This inhibition was due to a decline in epithelial proliferation and differentiation, as the mesenchymal layer was not affected by anti-KGF treatment. When KGF (100 ng/ml) was substituted for testosterone in the culture medium, SV growth was almost-qual-to 50% that observed with an optimal dose of testosterone (10(-7) M). All of these findings suggest that KGF is present during a time of active SV morphogenesis and functions as an important mediator of androgen-dependent development. C1 UNIV CALIF SAN FRANCISCO, DEPT ANAT, SAN FRANCISCO, CA 94143 USA. UNIV CALIF SAN FRANCISCO, CTR REPROD ENDOCRINOL, SAN FRANCISCO, CA 94143 USA. NCI, CELLULAR & MOLEC BIOL LAB, BETHESDA, MD 20892 USA. TECHNION ISRAEL INST TECHNOL, DEPT BIOL, IL-32000 HAIFA, ISRAEL. FU NIDDK NIH HHS [DK 32157] NR 39 TC 175 Z9 177 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 1 PY 1994 VL 91 IS 3 BP 1074 EP 1078 DI 10.1073/pnas.91.3.1074 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MV278 UT WOS:A1994MV27800052 PM 8302834 ER PT J AU DEMATTEIS, MA DIGIROLAMO, M COLANZI, A PALLAS, M DITULLIO, G MCDONALD, LJ MOSS, J SANTINI, G BANNYKH, S CORDA, D LUINI, A AF DEMATTEIS, MA DIGIROLAMO, M COLANZI, A PALLAS, M DITULLIO, G MCDONALD, LJ MOSS, J SANTINI, G BANNYKH, S CORDA, D LUINI, A TI STIMULATION OF ENDOGENOUS ADP-RIBOSYLATION BY BREFELDIN-A SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GTP-BINDING-PROTEINS; PERIPHERAL MEMBRANE-PROTEIN; SKELETAL-MUSCLE; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; GUANINE-NUCLEOTIDE; REGULATORY COMPONENT; ADENYLATE-CYCLASE; GOLGI-APPARATUS; CELLS; RIBOSYLTRANSFERASE AB Brefeldin A (BFA) is a fungal metabolite that exerts profound and generally inhibitory actions on membrane transport. At least some of the BFA effects are due to inhibition of the GDP-GTP exchange on the ADP-ribosylation factor (ARF) catalyzed by membrane protein(s). ARF activation is likely to be a key event in the association of non-clathrin coat components, including ARF itself, onto transport organelles. ARF, in addition to participating in membrane transport, is known to function as a cofactor in the enzymatic activity of cholera toxin, a bacterial ADP-ribosyltransferase. In this study we have examined whether BFA, in addition to inhibiting membrane transport, might affect endogenous ADP-ribosylation in eukaryotic cells. Two cytosolic proteins of 38 and 50 kDa were enzymatically ADP-ribosylated in the presence of BFA in cellular extracts. The 38-kDa substrate was tentatively identified as the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase. The BFA-binding components mediating inhibition of membrane traffic and stimulation of ADP-ribosylation appear to have the same ligand specificity. These data demonstrate the existence of a BFA-sensitive mono(ADP-ribosyl)transferase that may play a role in membrane movements. C1 CONSORZIO MARIO NEGRI SUD,IST RIC FARMACOL MARIO NEGRI,MOLEC & CELLULAR ENDOCRINOL LAB,I-66030 SANTA MARIA IMBAR,ITALY. CONSORZIO MARIO NEGRI SUD,IST RIC FARMACOL MARIO NEGRI,MOLEC NEUROBIOL LAB,I-66030 SANTA MARIA IMBAR,ITALY. NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892. RP DEMATTEIS, MA (reprint author), CONSORZIO MARIO NEGRI SUD,IST RIC FARMACOL MARIO NEGR,PHYSIOPATHOL SECRET LAB,I-66030 SANTA MARIA IMBAR,ITALY. RI Colanzi, Antonino/D-6821-2012; Pallas, Merce /H-3129-2016; Luini, Alberto/L-1372-2013; Corda, Daniela/K-6385-2016 OI Pallas, Merce /0000-0003-3095-4254; Luini, Alberto/0000-0002-8729-2549; Corda, Daniela/0000-0002-3614-751X NR 49 TC 64 Z9 64 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 FEB 1 PY 1994 VL 91 IS 3 BP 1114 EP 1118 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MV278 UT WOS:A1994MV27800060 PM 8302839 ER PT J AU ROMERO, R GONZALEZ, R BAUMANN, P BEHNKE, E RITTENHOUSE, L BARBERIO, D COTTON, DB MITCHELL, MD AF ROMERO, R GONZALEZ, R BAUMANN, P BEHNKE, E RITTENHOUSE, L BARBERIO, D COTTON, DB MITCHELL, MD TI TOPOGRAPHIC DIFFERENCES IN AMNIOTIC-FLUID CONCENTRATIONS OF PROSTANOIDS IN WOMEN IN SPONTANEOUS LABOR AT TERM SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article ID HUMAN PARTURITION; PROSTAGLANDINS; ENDOTOXIN; PLASMA AB These studies were designated to determine if there are differences in prostanoid concentrations between amniotic fluid (AF) retrieved transvaginally from the membrane forebag (lower or forebag compartment) and fluid retrieved by transabdominal amniocentesis from the 'upper compartment' in women in labor. Fluid was retrieved from 53 women in active labor who underwent transabdominal and transvaginal amniocentesis. Fluid was assayed for prostaglandin E(2) (PGE(2)) and prostaglandin F-2 alpha (PGF(2 alpha)), 13,14-dihydro-15-keto-prostaglandin F-2 alpha (PGFM), thromboxane B-2 (TXB(2)), and 6-keto-prostaglandin F-1 alpha (6-k-PGF(1 alpha)) using sensitive and specific radioimmunoassays. Concentrations of all prostanoids measured were significantly higher in fluid retrieved by transvaginal than transabdominal amniocentesis; the magnitude of the increase (measured as the ratio of concentrations in the lower/upper compartment) was higher for PGF(2 alpha) and TXB(2) than for the other prostanoids measured; for each prostanoid measured, there was a significant correlation between the concentration in the upper and lower compartment. C1 NIH, PERINATOL BRANCH, BETHESDA, MD USA. UNIV UTAH, SALT LAKE CITY, UT USA. HOSP DR SOTERO DEL RIO, SANTIAGO, CHILE. RP ROMERO, R (reprint author), WAYNE STATE UNIV, HUTZEL HOSP, DETROIT MED CTR, DEPT OBSTET & GYNECOL, 4707 ST ANTOINE BLVD, DETROIT, MI 48201 USA. RI Mitchell, Murray/A-8639-2010 OI Mitchell, Murray/0000-0002-6167-7176 NR 13 TC 33 Z9 33 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 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD FEB PY 1994 VL 50 IS 2 BP 97 EP 104 DI 10.1016/0952-3278(94)90154-6 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA MW060 UT WOS:A1994MW06000007 PM 8171074 ER PT J AU SANTTI, R NEWBOLD, RR MAKELA, S PYLKKANEN, L MCLACHLAN, JA AF SANTTI, R NEWBOLD, RR MAKELA, S PYLKKANEN, L MCLACHLAN, JA TI DEVELOPMENTAL ESTROGENIZATION AND PROSTATIC NEOPLASIA SO PROSTATE LA English DT Review DE PROSTATIC CANCER; BENIGN PROSTATIC HYPERPLASIA; DIETHYLSTILBESTROL; ESTROGENS; DEVELOPMENT ID HORMONE-BINDING GLOBULIN; MIDDLE-AGED MEN; CALCULATED FREE TESTOSTERONE; STAGE-B ADENOCARCINOMA; DUCT-ACINAR DYSPLASIA; MALE-MICE; ATYPICAL HYPERPLASIA; BREAST-CANCER; INTRAEPITHELIAL NEOPLASIA; REPRODUCTIVE-TRACT AB The association of estrogens with benign prostatic hyperplasia and prostatic cancer has been widely studies, but no conclusive evidence exists for a role of estrogens in prostatic disease. This paper reviews the literature and describes studies which have sought to show a correlation of estrogens and alterations in the prostates of humans and experimental animal models. Using the developmentally estrogenized mouse model, we propose an alternative role for estrogens as a predisposing factor for prostatic diseases: estrogen exposure during development may initiate cellular changes in the prostate which would require estrogens and/or androgens later in life for promotion to hyperplasia or neoplasia. Thus, the critical time for estrogen action would be during the development of the prostatic tissue. we further suggest that estrogen-sensitive cells may remain in the prostate and be more responsive to estrogens later in life or less responsive to the normal controlling mechanisms of prostatic growth. (C) 1994 Wiley-Liss, Inc.* C1 NIEHS,DIV INTRAMURAL RES,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. UNIV TURKU,INST BIOMED,DEPT ANAT,SF-20520 TURKU,FINLAND. NR 153 TC 110 Z9 110 U1 3 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0270-4137 J9 PROSTATE JI Prostate PD FEB PY 1994 VL 24 IS 2 BP 67 EP 78 DI 10.1002/pros.2990240204 PG 12 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA MV950 UT WOS:A1994MV95000003 PM 7508622 ER PT J AU SMYTHE, JA NARDELLI, B CHATTERJEE, P GALLO, RC GERSHONI, JM AF SMYTHE, JA NARDELLI, B CHATTERJEE, P GALLO, RC GERSHONI, JM TI PRODUCTION OF LINEAR-POLYMERS OF HIV GP120-BINDING DOMAINS SO PROTEIN ENGINEERING LA English DT Letter DE CD4; HIV; MOLECULAR DECOYS; RECEPTOR MIMICS; THERAPY ID HUMAN IMMUNODEFICIENCY VIRUS; AIDS-RELATED COMPLEX; HUMAN CD4; T4 MOLECULE; BINDING; FRAGMENT; PATHOGENESIS; RETROVIRUS; RECEPTOR; PHASE-1 AB It has been demonstrated previously that molecular decoys of the acetylcholine receptor have therapeutic efficacy as antitoxins [Gershoni,J. and Aronheim,A. (1988) Proc. Natl Acad. Sci. USA, 85, 4087-4089], but surely a most challenging goal is to apply this approach towards the development of antiviral drugs. As viruses present multiple copies of their envelope proteins, it was proposed that polyvalent decoys could be advantageous. Here we report the design and expression of recombinant linear polymers of the HIV gp120-binding domains which are situated within the T-cell membrane protein CD4. Whereas the production of linear concatemers of CD4 variable domains is feasible, a number of conformational constraints must be considered when designing a polymeric molecule which retains biological function. Most significant is the contribution of domains flanking the binding site that apparently enable correct folding of the latter. C1 TEL AVIV UNIV,GEORGE S WISE FAC LIFE SCI,DEPT CELL RES & IMMUNOL,IL-69978 TEL AVIV,ISRAEL. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NYU MED CTR,DEPT MED,DIV IMMUNOL,NEW YORK,NY 10016. NR 15 TC 5 Z9 5 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 FEB PY 1994 VL 7 IS 2 BP 145 EP 147 DI 10.1093/protein/7.2.145 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA MT177 UT WOS:A1994MT17700001 PM 8170917 ER PT J AU FISHER, RJ FIVASH, M CASASFINET, J ERICKSON, JW KONDOH, A BLADEN, SV FISHER, C WATSON, DK PAPAS, T AF FISHER, RJ FIVASH, M CASASFINET, J ERICKSON, JW KONDOH, A BLADEN, SV FISHER, C WATSON, DK PAPAS, T TI REAL-TIME DNA-BINDING MEASUREMENTS OF THE ETS1 RECOMBINANT ONCOPROTEINS REVEAL SIGNIFICANT KINETIC DIFFERENCES BETWEEN THE P42 AND P51 ISOFORMS SO PROTEIN SCIENCE LA English DT Article DE BIACORE; CAM KINASE II; DNA BINDING; P42 ETSI; P51 ETSI; SEQUENCE-SPECIFIC BINDING; SURFACE PLASMON RESONANCE ID SEQUENCE-SPECIFIC BINDING; TRANSCRIPTIONAL ACTIVATION; PROTEIN ADSORPTION; GENE; DOMAIN; COMPLEX; FAMILY; MOTIF AB The sequence-specific DNA binding of recombinant p42 and p51 ETS1 oncoprotein was examined quantitatively to determine whether the loss of the Exon VII phosphorylation domain in p42 ETS1 or the phosphorylation of expressed Exon VII in p51 ETS1 had an effect on DNA binding activity. The kinetics of sequence-specific DNA binding was measured using real-time changes in surface plasmon resonance with BIAcore (registered trademark, Pharmacia Biosensor) technology. The real-time binding of p42 and p51 ETS1 displayed significant differences in kinetic behavior, p51 ETS1 is characterized by a fast initial binding and conversion to a stable complex, whereas p42 ETS1 exhibits a slow initial binding and conversion to a stable complex. All of the p51 ETS1 DNA binding states are characterized by rapid turnover, whereas the p42 ETS1 DNA binding states are 4-20 times more stable. A model describing these kinetic steps is presented. Stoichiometric titrations of either p42 or p51 ETS1 with spe specific oligonucleotides show 1:1 complex formation. The DNA sequence specificity of the p42 and p51 ETS1 as determined by mutational analysis was similar. The in vitro phosphorylation of p51 ETS1 by CAM kinase II obliterates its binding to specific DNA, suggesting that the regulation of p51 ETS1 sequence-specific DNA binding occurs through phosphorylation by a calcium-dependent second messenger. The p42 ETS1 lacks this regulatory domain (Exon VII), and binding to its specific DNA sequence is not sensitive to calcium signaling. C1 NCI,FREDERICK CANC RES & DEV CTR,DATA MANAGEMENT SERV INC,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK BIOMED SUPERCOMP CTR,FREDERICK,MD 21702. NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702. RP FISHER, RJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,CELLULAR BIOCHEM LAB,BLDG 469,FREDERICK,MD 21702, USA. RI Fisher, Robert/B-1431-2009 NR 31 TC 129 Z9 130 U1 1 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD FEB PY 1994 VL 3 IS 2 BP 257 EP 266 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MZ675 UT WOS:A1994MZ67500010 PM 8003962 ER PT J AU KOONIN, EV AF KOONIN, EV TI CONSERVED SEQUENCE PATTERN IN A WIDE VARIETY OF PHOSPHOESTERASES SO PROTEIN SCIENCE LA English DT Article DE CONSERVED SEQUENCE PATTERN; PHOSPHOESTERASES ID ALKALINE-PHOSPHATASE; ACID-PHOSPHATASE; EXPRESSION; CLONING; ENZYME; GENE AB A unique sequence pattern, designated the GD/GNH signature, was shown to be conserved in a wide variety of phosphoesterases. The enzymes containing this signature cleave phosphoester bonds in such different substrates as (1) phosphoserine and phosphothreonine in polypeptides; (2) bis (5'-nucleosidyl)-tetraphosphates; (3) nucleoside 5' phosphates; (4) 2',3'-cyclic nucleotide phosphates; (5) polynucleotides; (6) 2'-5' phosphodiesters in RNA (intron) lariats; (7) sphingomyelin; and (7) various phosphomonoesters. Two conserved acidic amino acid residues and a conserved histidine residue may be directly involved in phosphoester bond cleavage. RP KOONIN, EV (reprint author), NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BLDG 38A,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 18 TC 97 Z9 98 U1 1 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD FEB PY 1994 VL 3 IS 2 BP 356 EP 358 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MZ675 UT WOS:A1994MZ67500018 PM 8003970 ER PT J AU GEORGE, MS ROSENSTEIN, D RUBINOW, DR KLING, MA POST, RM AF GEORGE, MS ROSENSTEIN, D RUBINOW, DR KLING, MA POST, RM TI CSF MAGNESIUM IN AFFECTIVE-DISORDER - LACK OF CORRELATION WITH CLINICAL COURSE OF TREATMENT SO PSYCHIATRY RESEARCH LA English DT Article DE CEREBROSPINAL FLUID; BIPOLAR DEPRESSION; CARBAMAZEPINE; LITHIUM ID CALCIUM; PLASMA; LITHIUM; ILLNESS; SERUM; MG-2+ AB There has been recent renewed interest in the role of magnesium in affective disorder, particularly in the bipolar subtype. However, determinations of serum magnesium concentrations have not yielded consistent findings and little is known about cerebrospinal fluid (CSF) magnesium in these patients. We analyzed CSF magnesium levels from 173 medication-free patients with affective disorder (76 bipolar I, 54 bipolar II, and 43 unipolar) and 59 healthy volunteers. In addition, we examined CSF magnesium from 32 patients before and during carbamazepine treatment and 13 patients before and during lithium treatment. CSF magnesium levels varied significantly according to gender (with lower concentrations in women) but not with respect to age, diagnosis, mood state, or treatment with carbamazepine or lithium. An abnormality of magnesium in affective disorders, if it exists, is not readily detectable in CSF. C1 NIMH,BIOL PSYCHIAT BRANCH,BEHAV ENDOCRINOL SECT,BETHESDA,MD 20892. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. RI Kling, Mitchel/F-4152-2010 OI Kling, Mitchel/0000-0002-2232-1409 NR 35 TC 12 Z9 13 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD FEB PY 1994 VL 51 IS 2 BP 139 EP 146 DI 10.1016/0165-1781(94)90033-7 PG 8 WC Psychiatry SC Psychiatry GA MZ741 UT WOS:A1994MZ74100004 PM 8022948 ER PT J AU ANDREASON, PJ ZAMETKIN, AJ GUO, AC BALDWIN, P COHEN, RM AF ANDREASON, PJ ZAMETKIN, AJ GUO, AC BALDWIN, P COHEN, RM TI GENDER-RELATED DIFFERENCES IN REGIONAL CEREBRAL GLUCOSE-METABOLISM IN NORMAL VOLUNTEERS SO PSYCHIATRY RESEARCH LA English DT Article DE POSITRON EMISSION TOMOGRAPHY; ORBITAL FRONTAL CORTEX; SEX DIFFERENCES; AGGRESSION; IMPULSIVITY ID OBSESSIVE-COMPULSIVE DISORDER; POSITRON EMISSION TOMOGRAPHY; PREFRONTAL CORTEX; BRAIN; RATES; DEPRESSION; MALES; PET AB Positron emission tomography studies have correlated changes in the cerebral metabolic rate of glucose utilization (CMRglu) with symptoms of depression, aggression, impulsivity, and hyperactivity. Psychiatric disorders in which these symptoms are manifested are disproportionately represented among the sexes. We evaluated gender differences in regional CMRglu in control subjects (21 men and 18 women) with particular interest in the global, orbital frontal, and left anterolateral prefrontal cortical (LAPFC) CMRglu. A trend was present for global CMRglu to be greater in women than in men. Regional CMRglu was lower in men than in women in the orbital frontal area. No differences were observed in the LAPFC region. C1 NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. NIH,CTR CLIN,DEPT NUCL MED,BETHESDA,MD 20892. RP ANDREASON, PJ (reprint author), NIAAA,CLIN STUDIES LAB,BLDG 10,RM 3C-102,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 26 TC 85 Z9 87 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD FEB PY 1994 VL 51 IS 2 BP 175 EP 183 DI 10.1016/0165-1781(94)90037-X PG 9 WC Psychiatry SC Psychiatry GA MZ741 UT WOS:A1994MZ74100008 PM 8022952 ER PT J AU RITZ, MC MANTIONE, CR LONDON, ED AF RITZ, MC MANTIONE, CR LONDON, ED TI SPERMINE INTERACTS WITH COCAINE BINDING-SITES ON DOPAMINE TRANSPORTERS SO PSYCHOPHARMACOLOGY LA English DT Article DE SPERMINE; COCAINE; BINDING SITES; DOPAMINE TRANSPORTERS ID D-ASPARTATE RECEPTOR; POLYAMINE RECOGNITION SITE; CENTRAL NERVOUS-SYSTEM; RAT-BRAIN; H-3 COCAINE; LIGAND-BINDING; STRIATAL MEMBRANES; XENOPUS OOCYTES; NMDA RECEPTOR; COMPLEX AB These studies were designed to assess the potential interaction of the polyamine spermine with cocaine binding to dopamine and serotonin transporters. The results of the experiments presented here indicate that spermine inhibits binding of the cocaine congener [H-3] CFT to striatal synaptosomal membranes. Further, although [H-3] CFT is known to interact with both dopamine and serotonin transporters, our results indicate that the observed inhibition of [H-3] CFT binding is likely to reflect a specific inhibition of binding to dopamine transporters. Spermine significantly inhibited the binding of both [H-3] CFT and [H-3] mazindol to dopamine transporters, while it had no apparent effects on the binding of the potent serotonin uptake inhibitor [H-3] paroxetine. Finally, saturation experiments show that the inhibition of ligand binding to the cocaine binding site on dopamine transporters appears not to be due to a modification of ligand affinity for the transporter, but to a decrease in the apparent density of ligand binding sites. The results of these experiments indicate that endogenously produced polyamines can alter cocaine binding to the dopamine transporter. The results are discussed in terms of possible impact on novel approaches for pharmacologically manipulating cocaine reinforcement and craving in clinical treatments for cocaine addiction, as well as for emergency treatment of cocaine overdose. C1 UNIV NEW MEXICO,CTR ALCOHOLISM SUBSTANCE ABUSE & ADDICT,ALBUQUERQUE,NM 87131. UNIV NEW MEXICO,ALBUQUERQUE,NM. UNIV NEW MEXICO,DEPT PSYCHOL,ALBUQUERQUE,NM 87131. RP RITZ, MC (reprint author), NATL INST DRUG ABUSE,ADDICT RES CTR,NEUROSCI BRANCH,NEUROIMAGING & DRUG ACT SECT,POB 5180,BALTIMORE,MD 21224, USA. NR 48 TC 7 Z9 7 U1 1 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD FEB PY 1994 VL 114 IS 1 BP 47 EP 52 DI 10.1007/BF02245443 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA MW866 UT WOS:A1994MW86600006 PM 7846207 ER PT J AU MABUCHI, K SODA, M RON, E TOKUNAGA, M OCHIKUBO, S SUGIMOTO, S IKEDA, T TERASAKI, M PRESTON, DL THOMPSON, DE AF MABUCHI, K SODA, M RON, E TOKUNAGA, M OCHIKUBO, S SUGIMOTO, S IKEDA, T TERASAKI, M PRESTON, DL THOMPSON, DE TI CANCER INCIDENCE IN ATOMIC-BOMB SURVIVORS .1. USE OF THE TUMOR REGISTRIES IN HIROSHIMA AND NAGASAKI FOR INCIDENCE STUDIES SO RADIATION RESEARCH LA English DT Article ID MORTALITY AB More than 30 years ago, population-based tumor registries were established in Hiroshima and Nagasaki. This report, the first of a series of papers on cancer incidence, describes methodological aspects of the tumor registries and discusses issues of data quality in the context of the Life Span Study (LSS) cohort, the major atomic bomb Survivor population. The tumor registries in Hiroshima and Nagasaki are characterized by active case ascertainment based on abstraction of medical records at area hospitals, augmented by tissue registries operational in the area and a number of clinical and pathological programs undertaken over the years among the atomic bomb survivors. Using conventional measures of quality, the Hiroshima and Nagasaki tumor registries have a death certificate-only (DCO) rate of less than 9%, a mortality/incidence (MII) ratio of about 50%, and a histological verification (HV) rate in excess of 70%, which place these registries among the best in Japan and comparable to many established registries worldwide. All tumor registry data pertaining to the LSS population were assembled, reviewed and handled with special attention given to the quality and uniformity of data based on standardized procedures. Special studies and monitoring programs were also introduced to evaluate the quality of the tumor incidence data in the LSS. Analyses were performed to examine the quality of incidence data overall and across various substrata used for risk assessment such as age, time and radiation dose groups. No significant associations were found between radiation dose and data quality as measured by various indices. These findings warrant the use of the present tumor registry-based data for studies of cancer incidence in the atomic bomb survivors. C1 RADIAT EFFECTS RES FDN,DEPT EPIDEMIOL,HIROSHIMA 732,JAPAN. RADIAT EFFECTS RES FDN,DEPT EPIDEMIOL PATHOL,NAGASAKI,JAPAN. NCI,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20892. HIROSHIMA CITY MED ASSOC,HIROSHIMA,JAPAN. HIROSHIMA PREFECTURAL MED ASSOC,HIROSHIMA,JAPAN. NAGASAKI UNIV,SCH MED,NAGASAKI 852,JAPAN. NAGASAKI CITY MED ASSOC,NAGASAKI,JAPAN. RADIAT EFFECTS RES FDN,DEPT STAT,HIROSHIMA 732,JAPAN. GEORGE WASHINGTON UNIV,CTR BIOSTAT,ROCKVILLE,MD. RP MABUCHI, K (reprint author), RADIAT EFFECTS RES FDN,DEPT EPIDEMIOL PATHOL,HIROSHIMA 732,JAPAN. FU NCPDCID CDC HHS [NCI NEC-4893-8-001] NR 46 TC 67 Z9 67 U1 0 U2 3 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD FEB PY 1994 VL 137 IS 2 SU S BP S1 EP S16 DI 10.2307/3578891 PG 16 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA MV400 UT WOS:A1994MV40000001 PM 8127951 ER PT J AU PRESTON, DL KUSUMI, S TOMONAGA, M IZUMI, S RON, E KURAMOTO, A KAMADA, N DOHY, H MATSUI, T NONAKA, H THOMPSON, DE SODA, M MABUCHI, K AF PRESTON, DL KUSUMI, S TOMONAGA, M IZUMI, S RON, E KURAMOTO, A KAMADA, N DOHY, H MATSUI, T NONAKA, H THOMPSON, DE SODA, M MABUCHI, K TI CANCER INCIDENCE IN ATOMIC-BOMB SURVIVORS .3. LEUKEMIA, LYMPHOMA AND MULTIPLE-MYELOMA, 1950-1987 SO RADIATION RESEARCH LA English DT Article ID SINGLE TREATMENT COURSE; ANKYLOSING-SPONDYLITIS; HODGKINS-DISEASE; X-RAYS; MORTALITY; RISK; RADIATION; RADIOTHERAPY; HIROSHIMA; NAGASAKI AB This paper presents an analysis of data on the incidence of leukemia, lymphoma and myeloma in the Life Span Study cohort of atomic bomb survivors during the period from late 1950 through the end of 1987 (93,696 survivors accounting for 2,778,000 person-years). These analyses add 9 additional years of follow-up for leukemia and 12 for myeloma to that in the last comprehensive reports on these diseases. This is the first analysis of the lymphoma incidence data in the cohort. Using both the Leukemia Registry and the Hiroshima and Nagasaki tumor registries, a total of 290 leukemia, 229 lymphoma and 73 myeloma cases were identified. The primary analyses were restricted to first primary tumors diagnosed among residents of the cities or surrounding areas with Dosimetry System 1986 dose estimates between 0 and 4 Gy kerma (231 leukemias, 208 lymphomas and 62 myelomas). Analyses focused on time-dependent models for the excess absolute risk. Separate analyses were carried out for acute lymphocytic leukemia (ALL), acute myelogenous leukemia (AML), chronic myeloeytic leukemia (CML) and adult T-cell leukemia (ATL). There were few cases of chronic lymphocytic leukemia in this population. There was strong evidence of radiation-induced risks for all subtypes except ATL, and there were significant subtype differences with respect to the effects of age at exposure and sex and in the temporal pattern of risk. The AML dose-response function was nonlinear, whereas there was no evidence against linearity for the other subtypes. When averaged over the follow-up period, the excess absolute risk (EAR) estimates (in cases per 10(4) PY Sv) for the leukemia subtypes were 0.6, 1.1 and 0.9 for ALL, AML and CML, respectively. The corresponding estimated average excess relative risks at 1 Sv are 9.1, 3.3 and 6.2, respectively. There was some evidence of an increased risk of lymphoma in males (EAR = 0.6 cases per 10(4) PY Sv) but no evidence of any excess in females. There was no evidence of an excess risk for multiple myeloma in our standard analyses. C1 RADIAT EFFECTS RES FDN,DEPT CLIN STUDIES,HIROSHIMA,HIROSHIMA,JAPAN. NAGASAKI UNIV,INST A BOMB,NAGASAKI,NAGASAKI,JAPAN. NCI,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20892. RADIAT EFFECTS RES FDN,DEPT EPIDEMIOL,HIROSHIMA 732,JAPAN. HIROSHIMA UNIV,NUCL MED & BIOL RES INST,HIROSHIMA,HIROSHIMA,JAPAN. HIROSHIMA A BOMB HOSP,DEPT INTERNAL MED,HIROSHIMA,HIROSHIMA,JAPAN. NAGASAKI CITY HOSP,DEPT INTERNAL MED,NAGASAKI,NAGASAKI,JAPAN. NAGASAKI CITY HOSP,DEPT INTERNAL MED,NAGASAKI,NAGASAKI,JAPAN. GEORGE WASHINGTON UNIV,CTR BIOSTAT,ROCKVILLE,MD 20852. RADIAT EFFECTS RES FDN,DEPT EPIDEMIOL PATHOL,NAGASAKI,NAGASAKI,JAPAN. RP PRESTON, DL (reprint author), RADIAT EFFECTS RES FDN,DEPT STAT,HIROSHIMA,HIROSHIMA,JAPAN. FU NCPDCID CDC HHS [NCI-4893-8-001] NR 64 TC 329 Z9 345 U1 3 U2 19 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD FEB PY 1994 VL 137 IS 2 SU S BP S68 EP S97 DI 10.2307/3578893 PG 30 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA MV400 UT WOS:A1994MV40000003 PM 8127953 ER PT J AU RON, E PRESTON, DL MABUCHI, K THOMPSON, DE SODA, M AF RON, E PRESTON, DL MABUCHI, K THOMPSON, DE SODA, M TI CANCER INCIDENCE IN ATOMIC-BOMB SURVIVORS .4. COMPARISON OF CANCER INCIDENCE AND MORTALITY SO RADIATION RESEARCH LA English DT Article AB This report compares cancer incidence and mortality among atomic bomb survivors in the Radiation Effects Research Foundation Life Span Study (LSS) cohort. Because the incidence data are derived from the Hiroshima and Nagasaki tumor registries, case ascertainment is limited to the time (1958-1987) and geographic restrictions (Hiroshima and Nagasaki) of the registries, whereas mortality data are available from 1950-1987 anywhere in Japan. With these conditions, there were 9,014 first primary incident cancer cases identified among LSS cohort members compared with 7,308 deaths for which cancer was listed as the underlying cause of death on death certificates. When deaths were limited to those occurring between 1958-1987 in Hiroshima or Nagasaki, there were 3,155 more incident cancer cases overall, and 1,262 more cancers of the digestive system. For cancers of the oral cavity and pharynx, skin, breast, female and male genital organs, urinary system and thyroid, the incidence series was at least twice as large as the comparable mortality series. Although the incidence and mortality data are dissimilar in many ways, the overall conclusions regarding which solid cancers provide evidence of a significant dose response generally confirm the mortality findings. When either incidence or mortality data are evaluated, significant excess risks are observed for all solid cancers, stomach, colon, liver (when it is defined as primary liver cancer or liver cancer not otherwise specified on the death certificate), lung, breast, ovary and urinary bladder. No significant radiation effect is seen for cancers of the pharynx, rectum, gallbladder, pancreas, nose, larynx, uterus, prostate or kidney in either series. There is evidence of a significant excess of nonmelanoma skin cancer in the incidence data, but not in the mortality series. Cancers of the salivary gland and thyroid are also in excess in the incidence series, but they were not evaluated in the earlier mortality analyses. For ah solid tumors the estimated excess relative risk at 1 Sv (ERR(1 Sv)) for incidence (ERR(1 Sv) = 0.63) is 40% larger than the excess relative risk (ERR) based on mortality data from 1950-1987 in all Japan (ERR(1 Sv) = 0.45). The corresponding excess absolute risk (EAR) point estimate is 2.7 times greater for incidence than mortality. For some cancer sites, the difference in the magnitude of risk between incidence and mortality is greater. These differences reflect the greater diagnostic accuracy of the incidence data and the lack of full representation of radiosensitive but relatively nonfatal cancers, such as breast and thyroid, in the mortality data. Analyses of both incidence and mortality data are needed since the two end points provide complementary information for risk assessment. C1 RADIAT EFFECTS RES FDN,DEPT EPIDEMIOL,HIROSHIMA 732,JAPAN. NCI,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20892. RADIAT EFFECTS RES FDN,DEPT STAT,HIROSHIMA 732,JAPAN. RADIAT EFFECTS RES FDN,DEPT EPIDEMIOL,HIROSHIMA 732,JAPAN. GEORGE WASHINGTON UNIV,CTR BIOSTAT,ROCKVILLE,MD. RADIAT EFFECTS RES FDN,DEPT EPIDEMIOL PATHOL,NAGASAKI,NAGASAKI,JAPAN. FU NCPDCID CDC HHS [NCI-4893-8-001] NR 19 TC 39 Z9 40 U1 0 U2 1 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD FEB PY 1994 VL 137 IS 2 SU S BP S98 EP S112 DI 10.2307/3578894 PG 15 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA MV400 UT WOS:A1994MV40000004 PM 8127954 ER PT J AU THOMPSON, DE MABUCHI, K RON, E SODA, M TOKUNAGA, M OCHIKUBO, S SUGIMOTO, S IKEDA, T TERASAKI, M IZUMI, S PRESTON, DL AF THOMPSON, DE MABUCHI, K RON, E SODA, M TOKUNAGA, M OCHIKUBO, S SUGIMOTO, S IKEDA, T TERASAKI, M IZUMI, S PRESTON, DL TI CANCER INCIDENCE IN ATOMIC-BOMB SURVIVORS .2. SOLID TUMORS, 1958-1987 SO RADIATION RESEARCH LA English DT Review ID X-RAY THERAPY; INDUCED SKIN-CANCER; LOS-ANGELES COUNTY; BREAST-CANCER; ANKYLOSING-SPONDYLITIS; TUBERCULOSIS PATIENTS; THYROID NEOPLASIA; PAROTID-GLAND; MORTALITY; RADIATION AB This report presents, for the first time, comprehensive data on the incidence of solid cancer and risk estimates for A-bomb survivors in the extended Life Span Study (LSS-E85) cohort. Among 79,972 individuals, 8613 first primary solid cancers were diagnosed between 1958 and 1987. As part of the standard registration process of the Hiroshima and Nagasaki tumor registries, cancer cases occurring among members of the LSS-E85 cohort were identified using a computer linkage system supplemented by manual searches. Special efforts were made to ensure complete case ascertainment, data quality and data consistency in the two cities. For all sites combined, 75% of the cancers were verified histologically, 6% were diagnosed by direct observation, 8% were based on a clinical diagnosis, and 12.6% were ascertained by death certificate only. A standard set of analyses was carried out for each of the organs and organ systems considered. Depending on the cancer site, Dosimetry System 1986 (DS86) organ or kerma doses were used for computing risk estimates. Analyses were based on a general excess relative risk model (the background rate times one plus the excess relative risk). Analyses carried out for each site involved fitting the background model with no dose effect, a linear dose-response model with no effect modifiers, a linear-quadratic dose-response model with no effect modifiers, and a series of linear dose-response models that included each of the covariates (sex, age at exposure, time since exposure, attained age and city) individually as effect modifiers. Because the tumor registries ascertain cancers in the registry catchment areas only, an adjustment was made for the effects of migration. In agreement with prior LSS findings, a statistically significant excess risk for all solid cancers was demonstrated [excess relative risk at 1 Sv (ERR(1 Sv)) = 0.63; excess absolute risk (EAR) per 10(4) person-year sievert (PY Sv) = 29.7]. For cancers of the stomach (ERR(1 Sv) = 0.32), colon (ERR(1 Sv) = 0.72), lung (ERR(1 Sv) = 0.95), breast (ERR(1 Sv) = 1.59), ovary (ERR(1 Sv) = 0.99), urinary bladder (ERR(1 Sv) = 1.02) and thyroid (ERR(1 Sv) = 1.15), significant radiation associations were observed. There was some indication of an increase in tumors of the neural tissue (excluding the brain) among persons exposed to the bombs before age 20. For the first time, radiation has been associated with liver (ERR(1 Sv) = 0.49) and nonmelanoma skin (ERR(1 Sv) = 1.0) cancer incidence in the LSS cohort. The present analysis also strengthened earlier findings, based on a smaller number of cases, of an effect of A-bomb radiation on salivary gland cancer. There was no significant radiation effect for cancers of the oral cavity and pharynx as a group, esophagus, rectum, gallbladder, pancreas, larynx, uterine cervix, uterine corpus, prostate, kidney and renal pelvis. Analyses of solid tumors individually and in combination revealed no appreciable differences between Hiroshima and Nagasaki (P > 0.5). The combined solid tumor analysis demonstrated a twofold greater relative risk for females than males and a trend for a decreasing relative risk with increasing age at exposure (P < 0.001). Females had a higher relative risk of cancers of the lung, total respiratory system and urinary system than males. The excess relative risk decreased with increasing age at exposure for combined digestive, stomach, nonmelanoma skin, breast and thyroid cancers. For solid cancers combined, the excess cancer risk increased with increasing attained age and was proportional to the background incidence rate. Unadjusted for age at exposure, the excess relative risk for most sites tended to decrease with increasing attained age. For some cancers (colon, breast, central nervous system and kidney) models that allowed the excess relative risk to vary with attained age fit at least as well as models that included age-at-exposure effects. For all solid tumors, excess cancers increased with time since exposure, based on an absolute excess risk model. Averaged over all ages at exposure, the relative risk decreased with time since exposure. Examination of temporal patterns by age-at-exposure groups suggested that the excess relative risk decreased with time for the younger age-at-exposure groups and remained virtually constant for the older cohorts. The LSS has served as one of the major sources of data used for cancer risk estimation. Previous studies focused primarily on the association between cancer mortality and radiation exposure. Although these mortality studies are extremely valuable, the accuracy of cancer diagnoses is limited, and death certificates do not provide adequate information on cancers with relatively high survival rates. Although incidence data also have their limitations (e.g., incomplete case ascertainment and partial reliance on death certificate diagnoses), they can provide more complete data on cancers with good survival, on histological type and on time from exposure to cancer onset. Thus future analyses of atomic bomb survivors should focus on both cancer mortality and incidence. C1 RADIAT EFFECTS RES FDN,DEPT EPIDEMIOL PATHOL,NAGASAKI,JAPAN. GEORGE WASHINGTON UNIV,CTR BIOSTAT,DEPT EPIDEMIOL PATHOL,ROCKVILLE,MD. RADIAT EFFECTS RES FDN,DEPT STAT,HIROSHIMA 732,JAPAN. RADIAT EFFECTS RES FDN,DEPT EPIDEMIOL,HIROSHIMA 732,JAPAN. RADIAT EFFECTS RES FDN,DEPT EPIDEMIOL PATHOL,HIROSHIMA,JAPAN. NCI,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20892. HIROSHIMA CITY MED ASSOC,HIROSHIMA,JAPAN. HIROSHIMA PREFECTURAL MED ASSOC,HIROSHIMA,JAPAN. NAGASAKI UNIV,SCH MED,NAGASAKI 852,JAPAN. NAGASAKI CITY MED ASSOC,NAGASAKI,JAPAN. FU NCPDCID CDC HHS [NCI-4893-8-001] NR 116 TC 415 Z9 434 U1 2 U2 16 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD FEB PY 1994 VL 137 IS 2 SU S BP S17 EP S67 DI 10.2307/3578892 PG 51 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA MV400 UT WOS:A1994MV40000002 PM 8127952 ER PT J AU CHOYKE, PL BUSH, W HARTMAN, D KING, B RUBIN, J SANDLER, C SCOUTT, L AF CHOYKE, PL BUSH, W HARTMAN, D KING, B RUBIN, J SANDLER, C SCOUTT, L TI GENITOURINARY RADIOLOGY SO RADIOLOGY LA English DT Article; Proceedings Paper CT 79th Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America (RSNA 93) CY NOV 28-DEC 03, 1993 CL CHICAGO, IL SP RADIOL SOC N AMER DE BLADDER NEOPLASMS, STAGING; CONTRAST MEDIA, EFFECTS; KIDNEY NEOPLASMS, DIAGNOSIS; KIDNEY, TRANSPLANTATION; MAGNETIC RESONANCE (MR), VASCULAR STUDIES; PREGNANCY, US; PROSTATE, NEOPLASMS; RADIOLOGICAL SOCIETY OF NORTH AMERICA, 79TH SCIENTIFIC ASSEMBLY AND ANNUAL MEETING; RENAL ARTERIES, STENOSIS OR OBSTRUCTION C1 UNIV WASHINGTON,SEATTLE,WA. PENN STATE UNIV,HERSHEY,PA. MAYO CLIN,ROCHESTER,MN. UNIV MICHIGAN,ANN ARBOR,MI. UNIV TEXAS,HOUSTON,TX. YALE UNIV,NEW HAVEN,CT. RP CHOYKE, PL (reprint author), NIH,BETHESDA,MD, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 1994 VL 190 IS 2 BP 598 EP 603 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA MW444 UT WOS:A1994MW44400066 PM 8284426 ER PT J AU LOCKSHIN, MD AF LOCKSHIN, MD TI ANTIPHOSPHOLIPID ANTIBODY SYNDROME SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Review ID SYSTEMIC LUPUS-ERYTHEMATOSUS; ANTICARDIOLIPIN ANTIBODIES; FETAL DEATH; LIVEDO RETICULARIS; CEREBRAL-ISCHEMIA; PREGNANT-WOMEN; YOUNG-PEOPLE; ANTICOAGULANT; DISEASE; ASSOCIATION RP LOCKSHIN, MD (reprint author), NIAMSD,EXTRAMURAL PROGRAM,BLDG 31,ROOM 4C-32,BETHESDA,MD 20892, USA. NR 75 TC 77 Z9 82 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD FEB PY 1994 VL 20 IS 1 BP 45 EP 59 PG 15 WC Rheumatology SC Rheumatology GA MX696 UT WOS:A1994MX69600004 PM 8153404 ER PT J AU MARSH, L SUDDATH, RL HIGGINS, N WEINBERGER, DR AF MARSH, L SUDDATH, RL HIGGINS, N WEINBERGER, DR TI MEDIAL TEMPORAL-LOBE STRUCTURES IN SCHIZOPHRENIA - RELATIONSHIP OF SIZE TO DURATION OF ILLNESS SO SCHIZOPHRENIA RESEARCH LA English DT Article DE MEDIAL TEMPORAL LOBE; HIPPOCAMPUS; AMYGDALA; MRI; (SCHIZOPHRENIA) ID HIPPOCAMPAL PYRAMIDAL CELL; NUCLEAR MAGNETIC-RESONANCE; BIPOLAR AFFECTIVE-DISORDER; FOLLOW-UP; LIMBIC SYSTEM; VENTRICULAR ENLARGEMENT; PARAHIPPOCAMPAL GYRUS; CEREBROSPINAL-FLUID; GENDER DIFFERENCES; BRAIN MORPHOLOGY AB Reductions in the size of medial temporal lobe structures in schizophrenia have been demonstrated using magnetic resonance imaging. It is not clear whether these neuropathological changes are present premorbidly or if they reflect an adult-onset progressive process. In this study, quantitative measures were made of the lateral ventricles, third ventricle, amygdala, hippocampus, and cerebral hemispheres from coronal MRI images on 33 patients with schizophrenia and 41 normal controls. Images were selected a priori from the region of the temporal lobe in which we had previously demonstrated reduced volume of temporal lobe gray matter in a separate sample of patients. Results showed a decrease in amygdala, hippocampal, and amygdala-hippocampal size bilaterally and an increase in third and lateral ventricular volume. Advancing age in normals was associated with a decrease in the size of medial temporal structures and an increase in lateral ventricular size. In schizophrenia, there was a correlation between age and lateral ventricle size, but duration of illness was not associated with reductions in medial temporal tissue or ventricular enlargement. These results are consistent with prior evidence from neuroimaging and postmortem studies of medial temporal pathology in schizophrenia and support hypotheses that neuropathological changes in schizophrenia are not progressive. C1 NIMH,NEUROSCI CTR ST ELIZABETHS,DIV INTRAMURAL RES,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NR 83 TC 123 Z9 123 U1 3 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD FEB PY 1994 VL 11 IS 3 BP 225 EP 238 DI 10.1016/0920-9964(94)90016-7 PG 14 WC Psychiatry SC Psychiatry GA MW590 UT WOS:A1994MW59000003 PM 8193061 ER PT J AU EGAN, MF DUNCAN, CC SUDDATH, RL KIRCH, DG MIRSKY, AF WYATT, RJ AF EGAN, MF DUNCAN, CC SUDDATH, RL KIRCH, DG MIRSKY, AF WYATT, RJ TI EVENT-RELATED POTENTIAL ABNORMALITIES CORRELATE WITH STRUCTURAL BRAIN ALTERATIONS AND CLINICAL-FEATURES IN PATIENTS WITH CHRONIC-SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Article DE P300; TEMPORAL LOBE; EVENT-RELATED POTENTIAL; HIPPOCAMPUS; N200; (SCHIZOPHRENIA) ID NEGATIVE SYMPTOMS; P300; TOPOGRAPHY; MEDICATION; ATTENTION; CORTEX AB Patients with schizophrenia appear to have abnormalities in both brain structures and information processing. Several recent reports have suggested that correlations exist between such measures. We examined the volume of several brain regions using magnetic resonance imaging (MRI), and also assessed both information processing, using brain event-related potentials (ERPs), and clinical symptomatology in sixteen medicated patients with schizophrenia. Subjects were tested using auditory and visual discrimination tasks. From the ERPs elicited by stimuli presented with relative probabilities of 0.1, the N100, N200, and P300 components were identified and measured. All subjects also had MRI scans that included 12 contiguous coronal sections, each 1 cm thick. From these scans, the following structures were identified and the volume or area quantified: third ventricle, lateral ventricles (partial), amygdala and hippocampus (one slice), partial brain volume (in one slice through the parietal lobe), and total prefrontal and temporal lobe gray and white matter in both cortical regions. Significant correlations were found between hippocampal area and the amplitude of the auditory and visual N200, and between the right hippocampus and the visual P300. Lower but significant correlations were seen between auditory P300 and measures of left temporal lobe structures. Auditory P300 amplitude correlated inversely with positive symptoms of schizophrenia. These preliminary results suggest that the ERP abnormalities in patients with schizophrenia are associated with temporal lobe pathology. C1 NIMH,PSYCHOL & PSYCHOPATHOL LAB,BETHESDA,MD 20892. RP EGAN, MF (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032, USA. NR 46 TC 109 Z9 111 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD FEB PY 1994 VL 11 IS 3 BP 259 EP 271 DI 10.1016/0920-9964(94)90020-5 PG 13 WC Psychiatry SC Psychiatry GA MW590 UT WOS:A1994MW59000007 PM 7910755 ER PT J AU GLOVINSKY, D KALOGERAS, KT KIRCH, DG SUDDATH, R WYATT, RJ AF GLOVINSKY, D KALOGERAS, KT KIRCH, DG SUDDATH, R WYATT, RJ TI CEREBROSPINAL-FLUID OXYTOCIN CONCENTRATION IN SCHIZOPHRENIC-PATIENTS DOES NOT DIFFER FROM CONTROL SUBJECTS AND IS NOT CHANGED BY NEUROLEPTIC MEDICATION SO SCHIZOPHRENIA RESEARCH LA English DT Article DE OXYTOCIN; NEUROLEPTIC; CEREBROSPINAL FLUID; (SCHIZOPHRENIA) ID VASOPRESSIN; MEMORY AB Cerebrospinal fluid (CSF) oxytocin concentrations in 20 neuroleptic-treated schizophrenic patients, 31 neuroleptic-withdrawn schizophrenic patients, and 15 normal control subjects were compared. Neither within-subject comparisons of CSF oxytocin concentration measurements made during neuroleptic treatment and withdrawal (n = 11), nor comparison of the combined neuroleptic-withdrawn and neuroleptic treated patient group (n = 40) with control subjects (n = 15) differed significantly, suggesting that CSF oxytocin concentration is not altered in schizophrenia. C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NIMH,DIV INTRAMURAL RES,BETHESDA,MD 20892. RP GLOVINSKY, D (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032, USA. NR 11 TC 43 Z9 44 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD FEB PY 1994 VL 11 IS 3 BP 273 EP 276 DI 10.1016/0920-9964(94)90021-3 PG 4 WC Psychiatry SC Psychiatry GA MW590 UT WOS:A1994MW59000008 PM 7910756 ER PT J AU GOLDBERG, TE WEINBERGER, DR AF GOLDBERG, TE WEINBERGER, DR TI SCHIZOPHRENIA, TRAINING PARADIGMS, AND THE WISCONSIN CARD SORTING TEST REDUX SO SCHIZOPHRENIA RESEARCH LA English DT Article DE WISCONSIN CARD SORTING TEST; TRAINING PARADIGM; (SCHIZOPHRENIA) ID FRONTAL-LOBE DAMAGE; CEREBRAL BLOOD-FLOW; MONOZYGOTIC TWINS; TEST-PERFORMANCE; PREFRONTAL-TYPE; REMEDIATION; DEFICITS; IMAGERY; MEMORY; DISCORDANT AB The question of whether and to what extent poor performance on the Wisconsin Card Sorting Test (WCST) in patients with schizophrenia can be improved with coaching has been controversial. We review relevant studies with particular reference to the following issues: (1) can improvement occur? (2) if improvement does occur, what is its significance? and (3) what is the association between performance and neurophysiology? The studies indicate that in patients with schizophrenia performance can frequently be improved, but usually remains in the abnormal range. Similar results for memory measures have been reported in patients with amnesias or dementias of known neurological origin. This suggests that simple dichotomies between neurologic and psychological explanations of cognitive impairment and potential amelioration of such impairment may be inadequate. Comparisons of the results of studies using the WCST as a clinical tool with binary cut-off scores to define normal and abnormal, as a measure of neuropsychological function along a continuum, and as an activation stimulus to probe neurophysiology suggest that absolute WCST scores may not always accurately gauge the functional integrity of neural systems dedicated to the task. This situation may arise because of individual differences in endowment and in the capacity for neuronal compensation, as well as measurement error. Given these issues, caution is advised in the interpretation of WCST scores, which are best understood as representing a final common cognitive pathway that can be the product of diverse psychological, physiological, and neuroanatomic mechanisms. RP GOLDBERG, TE (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032, USA. NR 39 TC 48 Z9 48 U1 3 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD FEB PY 1994 VL 11 IS 3 BP 291 EP 296 DI 10.1016/0920-9964(94)90024-8 PG 6 WC Psychiatry SC Psychiatry GA MW590 UT WOS:A1994MW59000011 PM 8193066 ER PT J AU MERLINO, G AF MERLINO, G TI INTRODUCTION - TRANSGENIC MICE IN CANCER-RESEARCH SO SEMINARS IN CANCER BIOLOGY LA English DT Editorial Material RP MERLINO, G (reprint author), NCI,MATH BIOL LAB,9000 ROCKVILLE PIKE 37-2E24,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD FEB PY 1994 VL 5 IS 1 BP 1 EP 2 PG 2 WC Oncology SC Oncology GA MV851 UT WOS:A1994MV85100001 ER PT J AU MERLINO, G AF MERLINO, G TI REGULATORY IMBALANCES IN CELL-PROLIFERATION AND CELL-DEATH DURING ONCOGENESIS IN TRANSGENIC MICE SO SEMINARS IN CANCER BIOLOGY LA English DT Article DE APOPTOSIS; GROWTH FACTOR; ONCOGENESIS; TRANSGENIC MICE; TUMOR SUPPRESSOR ID GROWTH-FACTOR-ALPHA; TUMOR-SUPPRESSOR GENE; WILD-TYPE P53; C-MYC; TGF-ALPHA; MENETRIERS DISEASE; EPITHELIAL-CELLS; RAT FIBROBLASTS; LYMPHOID TUMORS; EGF RECEPTOR RP MERLINO, G (reprint author), NCI,MATH BIOL LAB,BLDG 37,ROOM 2E24,BETHESDA,MD 20892, USA. NR 62 TC 17 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD FEB PY 1994 VL 5 IS 1 BP 13 EP 20 PG 8 WC Oncology SC Oncology GA MV851 UT WOS:A1994MV85100003 PM 8186384 ER PT J AU TSOKOS, M AF TSOKOS, M TI THE DIAGNOSIS AND CLASSIFICATION OF CHILDHOOD RHABDOMYOSARCOMA SO SEMINARS IN DIAGNOSTIC PATHOLOGY LA English DT Article DE RHABDOMYOSARCOMA; DIAGNOSIS; CLASSIFICATION AB Although the typical subtypes of embryonal, botryoid, alveolar, and pleomorphic rhabdomyosarcoma are easily recognized by simple light microscopic examination, poorly differentiated forms are difficult to diagnose and classify. The availability of markers connoting simple myogenous or skeletal muscle differentiation has contributed tremendously to the diagnosis of even poorly differentiated rhabdomyosarcoma. Definition of typical and minimal ultrastructural criteria has also been instrumental. Proper classification of rhabdomyosarcoma into subtypes with prognostic significance has been a difficult task. Although most pathologists have accepted the original classification scheme of embryonal, botryoid, alveolar, and pleomorphic rhabdomyosarcoma, they have used variable histologic criteria to define the various subtypes. Most of the major discrepancies occurred in the definition of embryonal versus alveolar rhabdomyosarcoma, especially in those cases that required establishment of minimal criteria. For example, poorly differentiated round-cell rhabdomyosarcoma has frequently been erroneously classified as embryonal, because of the absence of an alveolar pattern. This variety has been recognized as a form of alveolar (solid alveolar) rhabdomyosarcoma by the National Cancer Institute (NCI) scheme. Comparative analysis of several proposed classification schemes has led to the establishment of well-defined criteria for the major subtypes of rhabdomyosarcoma and to the recognition of subtypes with prognostic significance. This is a US government work. There are no restrictions on its use. RP TSOKOS, M (reprint author), NIH,PATHOL LAB,BETHESDA,MD 20892, USA. NR 0 TC 56 Z9 59 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0740-2570 J9 SEMIN DIAGN PATHOL JI Semin. Diagn. Pathol. PD FEB PY 1994 VL 11 IS 1 BP 26 EP 38 PG 13 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA NC471 UT WOS:A1994NC47100004 PM 8202644 ER PT J AU BAMFORD, DH WICKNER, RB AF BAMFORD, DH WICKNER, RB TI ASSEMBLY OF DOUBLE-STRANDED-RNA VIRUSES - BACTERIOPHAGE PHI-6 AND YEAST VIRUS L-A SO SEMINARS IN VIROLOGY LA English DT Article DE ASSEMBLY; RNA PACKAGING; DSRNA VIRUSES; PHI-6; L-A ID POL FUSION PROTEIN; SACCHAROMYCES-CEREVISIAE; NUCLEOTIDE-SEQUENCE; NONSENSE MUTANTS; INFECTIOUS NUCLEOCAPSIDS; INVITRO REPLICATION; N-ACETYLTRANSFERASE; DSRNA GENOME; HOST-CELLS; PARTICLE C1 UNIV HELSINKI, DEPT GENET, SF-00014 HELSINKI, FINLAND. NIH, GENET SIMPLE EUKARYOTES SECT, BETHESDA, MD 20892 USA. RP BAMFORD, DH (reprint author), UNIV HELSINKI, INST BIOTECHNOL, POB 17, ARKADIANKATU 7, SF-00014 HELSINKI, FINLAND. NR 58 TC 12 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-5773 J9 SEMIN VIROL JI Semin. Virol. PD FEB PY 1994 VL 5 IS 1 BP 61 EP 69 DI 10.1006/smvy.1994.1007 PG 9 WC Virology SC Virology GA MX884 UT WOS:A1994MX88400007 ER PT J AU MANOLIO, TA KRONMAL, RA BURKE, GL POIRIER, V OLEARY, DH GARDIN, JM FRIED, LP STEINBERG, EP BRYAN, RN CODY, ME CRUISE, RG ETTINGER, WH FURBERG, CD HEISS, G KLOPFENSTEIN, HS LEFKOWITZ, DS LYLES, MF MITTELMARK, MB TELL, GS BOMMER, W LEE, M ROBBINS, J SCHENKER, M KUMANYIKA, S BUSH, TL CHABOT, J COMSTOCK, GW GERMAN, PS HILL, J KITTNER, SJ POWE, NR PRICE, TR ROCK, R SZKLO, M BONK, J KULLER, LH MCLAUGHLIN, B MEYER, P NEWMAN, A ORCHARD, TJ RUTAN, GH SCHULZ, R SMITH, VE WOLFSON, SK ANTONCULVER, H KNOLL, M KUROSAKI, T WONG, N POLAK, JF POTTER, J BOVILL, E CORNELL, E HOWARD, P TRACY, RP ENRIGHT, P TOOGOOD, S CALHOUN, K CALHOUN, H MONTAGUE, P RAUTAHARJU, F RAUTAHARJU, P FELLOWS, D HOLTZ, P KRAUT, M LEE, G MILLER, TJ SCHERTZ, L WILKINS, L YUE, N BORHANI, NO FITZPATRICK, AL HERMANSON, BK PSATY, BM SISCOVICK, DS SHEMANSKI, L WAHL, PW BILD, DE SAVAGE, PJ SMITH, P AF MANOLIO, TA KRONMAL, RA BURKE, GL POIRIER, V OLEARY, DH GARDIN, JM FRIED, LP STEINBERG, EP BRYAN, RN CODY, ME CRUISE, RG ETTINGER, WH FURBERG, CD HEISS, G KLOPFENSTEIN, HS LEFKOWITZ, DS LYLES, MF MITTELMARK, MB TELL, GS BOMMER, W LEE, M ROBBINS, J SCHENKER, M KUMANYIKA, S BUSH, TL CHABOT, J COMSTOCK, GW GERMAN, PS HILL, J KITTNER, SJ POWE, NR PRICE, TR ROCK, R SZKLO, M BONK, J KULLER, LH MCLAUGHLIN, B MEYER, P NEWMAN, A ORCHARD, TJ RUTAN, GH SCHULZ, R SMITH, VE WOLFSON, SK ANTONCULVER, H KNOLL, M KUROSAKI, T WONG, N POLAK, JF POTTER, J BOVILL, E CORNELL, E HOWARD, P TRACY, RP ENRIGHT, P TOOGOOD, S CALHOUN, K CALHOUN, H MONTAGUE, P RAUTAHARJU, F RAUTAHARJU, P FELLOWS, D HOLTZ, P KRAUT, M LEE, G MILLER, TJ SCHERTZ, L WILKINS, L YUE, N BORHANI, NO FITZPATRICK, AL HERMANSON, BK PSATY, BM SISCOVICK, DS SHEMANSKI, L WAHL, PW BILD, DE SAVAGE, PJ SMITH, P TI MAGNETIC-RESONANCE ABNORMALITIES AND CARDIOVASCULAR-DISEASE IN OLDER ADULTS - THE CARDIOVASCULAR HEALTH STUDY SO STROKE LA English DT Article DE EPIDEMIOLOGY; LEUKOENCEPHALOPATHY; MAGNETIC RESONANCE IMAGING; RISK FACTORS ID CEREBRAL BLOOD-FLOW; CEREBROVASCULAR RISK-FACTORS; WHITE-MATTER; COMPUTED-TOMOGRAPHY; BRAIN ATROPHY; AGING BRAIN; AGE; LESIONS; VOLUME; ATHEROSCLEROSIS AB Background and Purpose Cerebral magnetic resonance imaging often detects abnormalities whose significance is unknown. The prevalence and correlates of findings such as ventricular enlargement, sulcal widening, and increased white matter signal intensity were examined in 303 men and women aged 65 to 95 years participating in a multicenter study of cardiovascular disease. Methods Cerebral magnetic resonance imaging was performed and interpreted according to a standard protocol, and findings were correlated with measures of cardiovascular disease and its risk factors. Results Measures of cerebral atrophy increased with age and were greater in men than in women (each P<.01). Ventricular enlargement and sulcal widening were associated with prior stroke, hypertension, diabetes, and white race (each P<.03). Extent of white matter hyperintensity was associated with age, prior stroke, hypertension, and use of diuretics (each P<.004). On multivariate analysis, age, male gender, white race, and prior stroke retained strong associations with increased ventricular and sulcal scores. After adjustment for age, prior stroke, and other risk factors, white matter hyperintensity was associated with atherosclerosis as measured by increased internal carotid artery thickness on ultrasound. Conclusions Cerebral atrophy and white matter hyperintensity are common in the elderly and are associated with age, prior stroke, and known cardiovascular risk factors. Though these findings have been suggested to represent normal aging, their wide variability and associations with cardiovascular disease argue against their inevitability with advancing age and support the need to identify modifiable risk factors for these abnormalities. C1 UNIV WASHINGTON,DEPT BIOSTAT,SEATTLE,WA 98195. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. UNIV CALIF DAVIS,DEPT RADIOL,SACRAMENTO,CA. GEISINGER CLIN & MED CTR,DEPT RADIOL,DANVILLE,PA. UNIV CALIF IRVINE,DEPT MED,ORANGE,CA. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT RADIOL,BALTIMORE,MD 21205. UNIV PITTSBURGH,PITTSBURGH,PA. UNIV CALIF IRVINE,CTR ECHOCARDIOG READING,IRVINE,CA. GEISINGER MED CLIN,CTR ULTRASOUND READING,DANVILLE,PA. UNIV VERMONT,CENT BLOOD ANAL LAB,BURLINGTON,VT. NHLBI,PROJECT OFF,BETHESDA,MD. MAYO CLIN & MAYO FDN,CTR PULM FUNCT READING,ROCHESTER,MN. UNIV ALBERTA,CTR ELECTROCARDIOG READING,EDMONTON,AB,CANADA. JOHNS HOPKINS UNIV,CTR MAGNET RESONANCE IMAGING READING,BALTIMORE,MD. UNIV WASHINGTON,CTR COORDINATING,SEATTLE,WA. RP MANOLIO, TA (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,FED BLDG,RM 301,7550 WISCONSIN AVE,BETHESDA,MD 20892, USA. RI Bryan, R. Nick/P-1661-2014; Tell, Grethe/G-5639-2015; Newman, Anne/C-6408-2013 OI Tell, Grethe/0000-0003-1386-1638; Newman, Anne/0000-0002-0106-1150 FU NHLBI NIH HHS [N01-HC-85079, N01-HC-85080, N01-HC-85081] NR 48 TC 316 Z9 325 U1 0 U2 8 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 1994 VL 25 IS 2 BP 318 EP 327 PG 10 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA MU285 UT WOS:A1994MU28500009 PM 8303738 ER PT J AU SPIVAK, CE AF SPIVAK, CE TI DESENSITIZATION AND NONCOMPETITIVE BLOCKADE OF GABA(A) RECEPTORS IN VENTRAL MIDBRAIN NEURONS BY A NEUROSTEROID DEHYDROEPIANDROSTERONE-SULFATE SO SYNAPSE LA English DT Article DE INHIBITORY POSTSYNAPTIC CURRENTS (IPSCS); ION CHANNEL; PATCH CLAMP ID RAT HIPPOCAMPAL-NEURONS; AMINOBUTYRIC-ACID RESPONSES; CORTICAL-NEURONS; VOLTAGE-CLAMP; SYNAPTIC POTENTIALS; ACTIVATED CURRENTS; XENOPUS OOCYTES; A-RECEPTOR; BENZODIAZEPINE; CHANNELS AB Dehydroepiandrosterone sulfate (DHEAS) blocked the GABA(A) receptor noncompetitively in neurons grown in primary culture from the ventral midbrains of fetal rats. The apparent dissociation constant for this blockade was 4.5 mu M, and one molecule of DHEAS was sufficient to block the receptor. The affinity of the blocked receptor for GABA was diminished by about one half. The findings that the DHEAS caused no rectification of chloride currents and that it did not shorten the durations of open ion channels indicated that DHEAS did not act by occluding open ion channels. Neither did it diminish their conductance. DHEAS accelerated desensitization in at least one population of receptors, diminished the amplitudes of inhibitory postsynaptic currents, and shortened their decay time constants in a concentration dependent manner. RP SPIVAK, CE (reprint author), NATL INST DRUG ABUSE,ADDICT RES CTR,BALTIMORE,MD 21224, USA. NR 44 TC 45 Z9 46 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 0887-4476 J9 SYNAPSE JI Synapse PD FEB PY 1994 VL 16 IS 2 BP 113 EP 122 DI 10.1002/syn.890160205 PG 10 WC Neurosciences SC Neurosciences & Neurology GA MW829 UT WOS:A1994MW82900004 PM 7515198 ER PT J AU DAVIS, CD FARB, A THORGEIRSSON, SS VIRMANI, R SYNDERWINE, EG AF DAVIS, CD FARB, A THORGEIRSSON, SS VIRMANI, R SYNDERWINE, EG TI CARDIOTOXICITY OF HETEROCYCLIC AMINE FOOD MUTAGENS IN CULTURED MYOCYTES AND IN RATS SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID HEART-DISEASE; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; COOKED FOOD; DNA ADDUCTS; F344 RATS; CARCINOGEN; IDENTIFICATION; BINDING; 2-AMINO-3-METHYLIMIDAZO<4,5-F>QUINOLINE; POPULATIONS C1 ARMED FORCES INST PATHOL,DEPT CARDIOVASC PATHOL,WASHINGTON,DC 20306. RP DAVIS, CD (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 37 TC 21 Z9 21 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD FEB PY 1994 VL 124 IS 2 BP 201 EP 211 DI 10.1006/taap.1994.1024 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA MW431 UT WOS:A1994MW43100005 PM 8122265 ER PT J AU BOGUSKI, M MCENTYRE, J AF BOGUSKI, M MCENTYRE, J TI I THINK THEREFORE I PUBLISH SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Letter RP BOGUSKI, M (reprint author), NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 3 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 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD FEB PY 1994 VL 19 IS 2 BP 71 EP 71 DI 10.1016/0968-0004(94)90036-1 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MW616 UT WOS:A1994MW61600007 PM 7909178 ER PT J AU HENGEN, PN AF HENGEN, PN TI METHODS AND REAGENTS - DETERMINING DNA CONCENTRATIONS AND RESCUING PCR PRIMERS SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article RP HENGEN, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 2 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD FEB PY 1994 VL 19 IS 2 BP 93 EP 94 DI 10.1016/0968-0004(94)90042-6 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MW616 UT WOS:A1994MW61600013 PM 8160273 ER PT J AU UHL, GR BLUM, K NOBLE, E SMITH, S AF UHL, GR BLUM, K NOBLE, E SMITH, S TI D(2)-RECEPTOR GENES - THE CAUSE OR CONSEQUENCE OF SUBSTANCE-ABUSE - REPLY SO TRENDS IN NEUROSCIENCES LA English DT Letter C1 JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROL, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROSCI, BALTIMORE, MD 21205 USA. UNIV CALIF LOS ANGELES, SCH MED, ALCOHOL RES CTR, LOS ANGELES, CA 90024 USA. UNIV TEXAS, HLTH SCI CTR, DEPT PHARMACOL, SAN ANTONIO, TX 78284 USA. UNIV WISCONSIN, DEPT PSYCHOL, MADISON, WI 53706 USA. NIDR, ADDICT RES CTR, ETIOL LAB, BALTIMORE, MD 21224 USA. RP UHL, GR (reprint author), NIDA, ADDICT RES CTR, MOLEC NEUROBIOL BRANCH, BOX 5180, BALTIMORE, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD FEB PY 1994 VL 17 IS 2 BP 50 EP 51 PG 2 WC Neurosciences SC Neurosciences & Neurology GA MU986 UT WOS:A1994MU98600003 ER PT J AU DEVANE, WA AF DEVANE, WA TI NEW DAWN OF CANNABINOID PHARMACOLOGY SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Article ID RECEPTOR; CELLS; BRAIN RP DEVANE, WA (reprint author), NIMH,CELL BIOL LAB,BLDG 36,RM 3A-17,BETHESDA,MD 20892, USA. NR 24 TC 39 Z9 39 U1 0 U2 2 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 FEB PY 1994 VL 15 IS 2 BP 40 EP 41 DI 10.1016/0165-6147(94)90106-6 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MY560 UT WOS:A1994MY56000004 PM 8165721 ER PT J AU LIN, YP SHU, LL WRIGHT, S BEAN, WJ SHARP, GB SHORTRIDGE, KF WEBSTER, RG AF LIN, YP SHU, LL WRIGHT, S BEAN, WJ SHARP, GB SHORTRIDGE, KF WEBSTER, RG TI ANALYSIS OF THE INFLUENZA-VIRUS GENE POOL OF AVIAN SPECIES FROM SOUTHERN CHINA SO VIROLOGY LA English DT Article ID A H1N1 VIRUSES; HONG-KONG; EVOLUTIONARY PATHWAYS; STRAINS; ORIGIN; SWINE; TURKEYS; HEMAGGLUTININ; REASSORTMENT; TRANSMISSION C1 UNIV TENNESSEE, DEPT PATHOL, MEMPHIS, TN 38163 USA. ST JUDE CHILDRENS RES HOSP, DEPT VIROL MOLEC BIOL, MEMPHIS, TN 38101 USA. UNIV HONG KONG, DEPT MICROBIOL, HONG KONG, HONG KONG. NIAID, SCI REVIEW PROGRAM, BETHESDA, MD 20892 USA. UNIV TENNESSEE, DEPT BIOSTAT & EPIDEMIOL, MEMPHIS, TN 38163 USA. FU NCI NIH HHS [CA-21765]; NIAID NIH HHS [AI-29680] NR 49 TC 25 Z9 27 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD FEB 1 PY 1994 VL 198 IS 2 BP 557 EP 566 DI 10.1006/viro.1994.1067 PG 10 WC Virology SC Virology GA MV841 UT WOS:A1994MV84100015 PM 8291238 ER PT J AU KUBOTA, S OROSZLAN, S HATANAKA, M AF KUBOTA, S OROSZLAN, S HATANAKA, M TI THE ORIGIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REV GENE - AN EVOLUTIONARY HYPOTHESIS SO FEBS LETTERS LA English DT Article DE HIV-1; REV PROTEIN; RNA BINDING PROTEIN; LENTIVIRIDA ID INFECTIOUS-ANEMIA VIRUS; TRANS-ACTIVATOR; PROTEINS AB The Rev protein of human immunodeficiency virus type-1 is an RNA-binding posttranscriptional transregulator encoded by an accessory gene that is distinct from retroviral oncogenes and whose origin is unclear. We hypothesize that the a ev gene was generated by duplication of a viral RNA segment having a secondary-structure that evolved into the Rev-responsive element (RRE). This hypothesis is based on the following findings. First, accumulated data on functional mapping of Rev, Tat, and the transmembrane protein of Env suggested that the major coding exon of rev should have been inserted into the transmembrane region of env during the course of its evolution. Experiments with equine infectious anemia virus, another complex retrovirus, also indicate that a large portion of rev is located within the dispensable transmembrane region of env. Second, base usage analysis suggests the same origin for rev and RRE. Our hypothesis may provide a new insight into the evolutionary aspect of RNA-binding transactivators. C1 NCI,FREDERICK CANC RES & DEV CTR,MOLEC VIROL & CARCINOGENESIS LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. KYOTO UNIV,INST VIRUS RES,SAKYO KU,KYOTO 606,JAPAN. NR 12 TC 2 Z9 2 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 JAN 31 PY 1994 VL 338 IS 2 BP 118 EP 121 DI 10.1016/0014-5793(94)80347-1 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA MV966 UT WOS:A1994MV96600002 PM 8307167 ER PT J AU RIVEROLEZCANO, OM ROBBINS, KC AF RIVEROLEZCANO, OM ROBBINS, KC TI SPECIFICITY OF PROTEIN INTERACTIONS WITH HIGHLY RELATED SRC HOMOLOGY (SH) DOMAINS OF FGR AND FYN PROTEIN-TYROSINE KINASES SO FEBS LETTERS LA English DT Article DE PROTOONCOGENE; PROTEIN BINDING; TYROSINE PHOSPHORYLATION ID PHOSPHOTYROSINE-CONTAINING PROTEINS; PRODUCT; ONCOGENE; GENE; IDENTIFICATION; CELLS; ASSOCIATION; EXPRESSION; BINDING; REGION AB As an approach toward identification and isolation of cellular proteins that may act as substrates or effecters of the SRC-family of protein-tyrosine kinases, fusion proteins containing noncatalytic elements of two highly related SRC-family members were tested for their ability to recognize distinct molecules present in lysates of cells known to normally express both enzymes. Our results demonstrate differences of protein binding between the SH2 elements of FYN and FGR kinases, but do not discriminate proteins binding to their SH3 domains. C1 NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. RI Rivero-Lezcano, Octavio/J-9089-2015 OI Rivero-Lezcano, Octavio/0000-0002-8793-0731 NR 28 TC 9 Z9 9 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 JAN 31 PY 1994 VL 338 IS 2 BP 183 EP 186 DI 10.1016/0014-5793(94)80361-7 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA MV966 UT WOS:A1994MV96600016 PM 7508405 ER PT J AU WANG, JB JOHNSON, PS PERSICO, AM HAWKINS, AL GRIFFIN, CA UHL, GR AF WANG, JB JOHNSON, PS PERSICO, AM HAWKINS, AL GRIFFIN, CA UHL, GR TI HUMAN MU-OPIATE RECEPTOR - CDNA AND GENOMIC CLONES, PHARMACOLOGICAL CHARACTERIZATION AND CHROMOSOMAL ASSIGNMENT SO FEBS LETTERS LA English DT Article DE MORPHINE; HEROIN; PAIN; ADDICTION; ENKEPHALIN; G-LINKED RECEPTOR ID DELTA-OPIOID RECEPTOR; BINDING-SITES; INSITU HYBRIDIZATION; ADENYLATE-CYCLASE; BRAIN MEMBRANES; SH-SY5Y CELLS; RAT-BRAIN; KAPPA; DIFFERENTIATION; EXPRESSION AB A human mu opiate receptor cDNA has been identified from a cerebral cortical cDNA library using sequences from the rat mu opiate receptor cDNA. The human p opiate receptor (h mu OR1) shares 95% amino acid identity with the rat sequence. The expressed mu OR1 recognizes tested opiate drugs and opioid peptides in a sodium- and GTP-sensitive fashion with affinities virtually identical to those displayed by the rat mu opiate receptor. Effects on cyclic AMP are similar to those noted for the rat mu opiate receptor. An 18 kb genomic clone hybridizing with the h mu OR1 cDNA contains 63 and 489 bp exonic sequences flanked by splice donor/acceptor sequences. Analysis of hybridization to DNA prepared from human rodent hybrid cell lines and chromosomal in situ hybridization studies indicate localization to 6q24-25. An MspI polymorphism, producing a 3.7 kb band, may prove useful in assessing this gene's involvement in neuropsychiatric disorders involving opiatergic systems. C1 NIDA,ADDICT RES CTR,MOLEC NEUROBIOL BRANCH,BALTIMORE,MD 21224. JOHNS HOPKINS SCH MED,CTR ONCOL,BALTIMORE,MD. JOHNS HOPKINS SCH MED,DEPT NEUROL,BALTIMORE,MD. JOHNS HOPKINS SCH MED,DEPT NEUROSCI,BALTIMORE,MD. NR 46 TC 257 Z9 266 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JAN 31 PY 1994 VL 338 IS 2 BP 217 EP 222 DI 10.1016/0014-5793(94)80368-4 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA MV966 UT WOS:A1994MV96600023 PM 7905839 ER PT J AU BLAGOSKLONNY, MV NECKERS, LM AF BLAGOSKLONNY, MV NECKERS, LM TI CYTOSTATIC AND CYTOTOXIC ACTIVITY OF SEX STEROIDS AGAINST HUMAN LEUKEMIA-CELL LINES SO CANCER LETTERS LA English DT Article DE LEUKEMIAS; ESTROGENS; PROGESTINS; CYTOSTASIS; CYTOTOXICITY ID ESTROGEN-BINDING-SITES; RECEPTORS AB We investigated effects of sex steroids and analogs (estradiol, DES, norgestrel, progesterone, medroxyprogesterone, and testosterone) on the proliferation and survival of 10 human leukemia/lymphoma cell lines (HL-60, K562, U937, CEM, KG-1, Jurkat, U266, H929, PA and SUNHL). Micromolar concentrations of sex steroids exerted cytostatic and cytotoxic effects on all cell lines tested, irrespective of their sensitivity to glucocorticoids. The order of potency of sex hormones was: DES > progesterone greater than or equal to medroxyprogesterone > testosterone > estradiol >> norgestrel. For progesterone and estradiol, cytostatic effects can be achieved at lower concentrations than cytotoxic effects. The most potent agent, DES, exerted half maximal cytotoxic activity at a median concentration of 4 mu M (for 10 leukemia cell lines). Our results provide a basis for the potential therapeutic use of estrogens and progestins in glucocorticoid-resistant leukemias and lymphomas. RP BLAGOSKLONNY, MV (reprint author), NCI,CLIN PHARMACOL BRANCH,BLDG 10,ROOM 12 N226,BETHESDA,MD 20892, USA. NR 13 TC 26 Z9 26 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JAN 30 PY 1994 VL 76 IS 2-3 BP 81 EP 86 DI 10.1016/0304-3835(94)90381-6 PG 6 WC Oncology SC Oncology GA NA897 UT WOS:A1994NA89700001 PM 8149350 ER PT J AU PIEGORSCH, WW WEINBERG, CR TAYLOR, JA AF PIEGORSCH, WW WEINBERG, CR TAYLOR, JA TI NON-HIERARCHICAL LOGISTIC-MODELS AND CASE-ONLY DESIGNS FOR ASSESSING SUSCEPTIBILITY IN POPULATION-BASED CASE-CONTROL STUDIES SO STATISTICS IN MEDICINE LA English DT Article ID EPIDEMIOLOGIC APPROACH; FAMILIAL AGGREGATION; GENE; DISEASE; CANCER; DEBRISOQUINE; MUTATIONS; SARCOMA; ALLELES; LOCUS AB This article describes how genetic components of disease susceptibility can be evaluated in case-control studies, where cases and controls are sampled independently from the population at large. Subjects are assumed unrelated, in contrast to studies of familial aggregation and linkage. The logistic model can be used to test collapsibility over phenotypes or genotypes, and to estimate interactions between environmental and genetic factors. Such interactions provide an example of a context where non-hierarchical models make sense biologically. Also, if the exposure and genetic categories occur independently and the disease is rare, then analyses based only on cases are valid, and offer better precision for estimating gene environment interactions than those based on the full data. C1 NIEHS,DIV BIOMETRY & RISK ASSESSMENT,RES TRIANGLE PK,NC 27709. OI Piegorsch, Walter/0000-0003-2725-5604; taylor, jack/0000-0001-5303-6398 NR 37 TC 292 Z9 302 U1 2 U2 10 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 30 PY 1994 VL 13 IS 2 BP 153 EP 162 DI 10.1002/sim.4780130206 PG 10 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 MR193 UT WOS:A1994MR19300005 PM 8122051 ER PT J AU SACK, MN RADER, DJ CANNON, RO AF SACK, MN RADER, DJ CANNON, RO TI ESTROGEN AND INHIBITION OF OXIDATION OF LOW-DENSITY LIPOPROTEINS IN POSTMENOPAUSAL WOMEN SO LANCET LA English DT Note ID 17-BETA ESTRADIOL AB Oxidative modification of low-density lipoprotein (LDL) may be atherogenic. We studied the time of onset of LDL oxidation (lag) in 18 postmenopausal women before and after intraarterial infusion of 17beta-oestradiol, after 3 weeks' patch administration ir 12 of these women, and 1. month after discontinuation in 10. The lag increased from baseline after acute infusion (from 134 [SD 41] to 167 [36] min, p = 0.01) and after the patch (132 [31] to 178 [45] min, p = 0.009). After discontinuation of oestradiol, the lag returned to baseline. This study shows an antioxidant effect of physiological levels of 17beta-oestradiol, which may contribute to an anti-atherogenic action. C1 NHLBI,CARDIOL BRANCH,BLDG 10,ROOM 7B-15,BETHESDA,MD 20892. NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. GEORGETOWN UNIV HOSP,WASHINGTON,DC 20007. NR 9 TC 447 Z9 454 U1 0 U2 3 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JAN 29 PY 1994 VL 343 IS 8892 BP 269 EP 270 DI 10.1016/S0140-6736(94)91117-7 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA MT440 UT WOS:A1994MT44000015 PM 7905101 ER PT J AU VUKICEVIC, S LATIN, V CHEN, P BATORSKY, R REDDI, AH SAMPATH, TK AF VUKICEVIC, S LATIN, V CHEN, P BATORSKY, R REDDI, AH SAMPATH, TK TI LOCALIZATION OF OSTEOGENIC PROTEIN-1 (BONE MORPHOGENETIC PROTEIN-7) DURING HUMAN EMBRYONIC-DEVELOPMENT - HIGH-AFFINITY BINDING TO BASEMENT-MEMBRANES SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID OP-1; DIFFERENTIATION; PROLIFERATION; COLLAGEN; INVITRO; IV C1 SCH MED ZAGREB,DEPT GYNECOL,ZAGREB,CROATIA. NIDR,BONE RES BRANCH,BETHESDA,MD 20892. CREAT BIOMOLECULES INC,HOPKINTON,MA 01748. JOHNS HOPKINS UNIV,DEPT ORTHOPED SURG,BALTIMORE,MD 21205. RP VUKICEVIC, S (reprint author), SCH MED ZAGREB,DEPT ANAT,ZAGREB,CROATIA. NR 12 TC 178 Z9 181 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 28 PY 1994 VL 198 IS 2 BP 693 EP 700 DI 10.1006/bbrc.1994.1100 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MT888 UT WOS:A1994MT88800041 PM 8297380 ER PT J AU BLIN, J RAY, CA PIERCEY, MF BARTKO, JJ MOURADIAN, MM CHASE, TN AF BLIN, J RAY, CA PIERCEY, MF BARTKO, JJ MOURADIAN, MM CHASE, TN TI COMPARISON OF CHOLINERGIC DRUG EFFECTS ON REGIONAL BRAIN GLUCOSE CONSUMPTION IN RATS AND HUMANS BY MEANS OF AUTORADIOGRAPHY AND POSITRON EMISSION TOMOGRAPHY SO BRAIN RESEARCH LA English DT Article DE DEOXYGLUCOSE; SCOPOLAMINE; PHYSOSTIGMINE; ALZHEIMERS DISEASE ID ENERGY-METABOLISM; SCOPOLAMINE; PHYSOSTIGMINE; NICOTINE; PHARMACOKINETICS; VALIDATION; MEMORY AB Cholinergic mechanisms have been extensively studied in animals and have been implicated in the pathogenesis of human disorders such as Alzheimer's disease. However, few investigations have directly evaluated the validity of extrapolating the results of animal studies to humans. As a component of a continuing examination of the contribution of cholinergic deficits to the alterations in brain metabolism that occur in Alzheimer's disease, we have compared the effects of scopolamine and physostigmine on regional brain energy metabolism in both rats and humans, using a common region of interest atlas. In Alzheimer's patients and in rodents, physostigmine increased glucose metabolism in several regions (e.g. thalamus) and decreased it in others. Overall, there was a significant positive correlation for the effects of physostigmine in the nineteen brain regions studied in both species (r=0.51, P < 0.05). In normal humans, scopolamine induced a metabolic increase in most brain regions except in the thalamus. Outside this structure, the regional effects of scopolamine were significantly and negatively correlated (r=-0.58, P < 0.01) between rat and human. These results suggest that: (1) cholinergic mechanisms have a similar anatomic distribution in both species, (2) muscarinic receptor-mediated cholinergic effects could predominate outside the thalamus, (3) muscarinic mechanisms are inhibitory in humans but are more complex and possibly excitatory in rats, (4) nicotinic stimulatory effects are found in the thalamus of both species, and (5) physostigmine, but not scopolamine, alters glucose consumption similarly in both species. C1 NIH, EXPTL THERAPEUT BRANCH, BETHESDA, MD USA. UPJOHN CO, CNS RES, KALAMAZOO, MI 49001 USA. NIH, DIV BIOMETRY, BETHESDA, MD USA. OI Mouradian, M. Maral/0000-0002-9937-412X NR 31 TC 25 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD JAN 28 PY 1994 VL 635 IS 1-2 BP 196 EP 202 DI 10.1016/0006-8993(94)91439-7 PG 7 WC Neurosciences SC Neurosciences & Neurology GA MT887 UT WOS:A1994MT88700023 PM 8173955 ER PT J AU PAUL, WE SEDER, RA AF PAUL, WE SEDER, RA TI LYMPHOCYTE-RESPONSES AND CYTOKINES SO CELL LA English DT Review ID T-CELL SUBSETS; HUMAN INTERLEUKIN-4; INTERFERON-GAMMA; MURINE LEISHMANIASIS; MONOCLONAL-ANTIBODY; CRYSTAL-STRUCTURE; GROWTH-HORMONE; ACTIVATION; IL-4; MICE C1 NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. RP PAUL, WE (reprint author), NIAID,IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 73 TC 1579 Z9 1615 U1 4 U2 41 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JAN 28 PY 1994 VL 76 IS 2 BP 241 EP 251 DI 10.1016/0092-8674(94)90332-8 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MU678 UT WOS:A1994MU67800008 PM 7904900 ER PT J AU GERMAIN, RN AF GERMAIN, RN TI MHC-DEPENDENT ANTIGEN-PROCESSING AND PEPTIDE PRESENTATION - PROVIDING LIGANDS FOR T-LYMPHOCYTE ACTIVATION SO CELL LA English DT Review ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-II MOLECULES; HLA-DR MOLECULES; INVARIANT CHAIN; ENDOPLASMIC-RETICULUM; SELF-PEPTIDES; CELL RECEPTOR; CIS-GOLGI; SPECIFICITY; PROTEINS RP GERMAIN, RN (reprint author), NIAID,IMMUNOL LAB,LYMPHOCYTE BIOL SECT,BETHESDA,MD 20892, USA. NR 83 TC 1137 Z9 1158 U1 2 U2 47 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JAN 28 PY 1994 VL 76 IS 2 BP 287 EP 299 DI 10.1016/0092-8674(94)90336-0 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MU678 UT WOS:A1994MU67800012 PM 8293464 ER PT J AU STUDITSKY, VM CLARK, DJ FELSENFELD, G AF STUDITSKY, VM CLARK, DJ FELSENFELD, G TI A HISTONE OCTAMER CAN STEP AROUND A TRANSCRIBING POLYMERASE WITHOUT LEAVING THE TEMPLATE SO CELL LA English DT Article ID RNA-POLYMERASE; NUCLEOSOME CORE; CHROMATIN STRUCTURE; ELONGATION COMPLEXES; DNA-TEMPLATE; TRANSCRIPTION; GENE; DISPLACEMENT; RESOLUTION; EXPRESSION AB The mechanism by which nucleosome cores are displaced and re-formed during transcription in vitro has been investigated. A nucleosome core was assembled on a short linear DNA template (227 bp) containing an SP6 RNA polymerase promoter and a nucleosome-positioning sequence. Transcription induced the translocation of the nucleosome core over 75 or 80 bp to two positions at the other end of the template, blocking the promoter. At low rNTP concentrations, transfer occurred only on the same template molecule, even in the presence of large excesses of competitor DNA. On a longer template (262 bp), nucleosome core position after transcription depended on its position before transcription. The data suggest that the octamer transfers without dissociation from DNA and provide strong evidence for a translocation mechanism in which DNA ahead of the polymerase uncoils from the octamer as the DNA behind coils around it. In this way, the octamer steps around the transcribing polymerase. RP STUDITSKY, VM (reprint author), NIAID,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. RI Studitsky, Vasily/A-9382-2014 NR 42 TC 183 Z9 186 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JAN 28 PY 1994 VL 76 IS 2 BP 371 EP 382 DI 10.1016/0092-8674(94)90343-3 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MU678 UT WOS:A1994MU67800019 PM 8293470 ER PT J AU DANCIS, A YUAN, DS HAILE, D ASKWITH, C EIDE, D MOEHLE, C KAPLAN, J KLAUSNER, RD AF DANCIS, A YUAN, DS HAILE, D ASKWITH, C EIDE, D MOEHLE, C KAPLAN, J KLAUSNER, RD TI MOLECULAR CHARACTERIZATION OF A COPPER TRANSPORT PROTEIN IN SACCHAROMYCES-CEREVISIAE - AN UNEXPECTED ROLE FOR COPPER IN IRON TRANSPORT SO CELL LA English DT Article ID SACCHAROMYCES-CEREVISIAE; MEMBRANE-PROTEINS; FERRIC REDUCTASE; SHUTTLE VECTORS; YEAST; METALLOTHIONEIN; CERULOPLASMIN; RESISTANCE; SEQUENCE; SYSTEM AB We report the identification and characterization of CTR1, a gene in the yeast S. cerevisiae that encodes a multispanning plasma membrane protein specifically required for high affinity copper transport into the cell. The predicted protein contains a methionine- and serine-rich domain that includes 11 examples of the sequence Met-X2-Met, a motif noted in proteins involved in bacterial copper metabolism. CTR1 mutants and deletion strains have profound deficiency in ferrous iron uptake, thus revealing a requirement for copper in mediating ferrous transport into the cell. Genetic evidence suggests that the target for this requirement is the FET3 gene (detailed in a companion study), predicted to encode a copper-containing protein that acts as a cytosolic ferro-oxidase. These findings provide an unexpected mechanistic link between the uptake of copper and iron. C1 UNIV UTAH, COLL MED, DEPT PATHOL, DIV CELL BIOL & IMMUNOL, SALT LAKE CITY, UT 84132 USA. UNIV MINNESOTA, SCH MED, DEPT BIOCHEM & MOLEC BIOL, DULUTH, MN 55812 USA. NICHHD, MOLEC GENET LAB, BETHESDA, MD 20892 USA. RP NICHHD, CELL BIOL & METAB BRANCH, BETHESDA, MD 20892 USA. NR 43 TC 497 Z9 506 U1 2 U2 15 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD JAN 28 PY 1994 VL 76 IS 2 BP 393 EP 402 DI 10.1016/0092-8674(94)90345-X PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MU678 UT WOS:A1994MU67800021 PM 8293472 ER PT J AU RIDER, LG RABEN, N MILLER, L JELSEMA, C AF RIDER, LG RABEN, N MILLER, L JELSEMA, C TI THE CDNAS ENCODING 2 FORMS OF THE LYN PROTEIN-TYROSINE KINASE ARE EXPRESSED IN RAT MAST-CELLS AND HUMAN MYELOID CELLS SO GENE LA English DT Note DE ALTERNATIVE SPLICING; GENE FAMILY; SEQUENCE HOMOLOGY; PHOSPHORYLATION ID AMINO-TERMINAL DOMAIN; SRC FAMILY; ISOFORMS; P59FYN; P56LCK; RNA; CD4 AB Two isoforms of lck/yes-related novel (LYN) protein tyrosine kinase (PTK) appear to play a role in B-cell-IgM and Fc(E)RI receptor signaling. The cDNAs lynA and lynB encoding these two forms were isolated and sequenced; they were derived from rat mucosal mast cell and human myeloid cell lines. The nucleotide (nt) and deduced amino acid (aa) sequences share 94 and 97% identity between rat and mouse lyn, respectively, and 88 and 96% identity between rat and human lyn. In all three species, a region of 20 aa is uniformly inserted at an identical site and its sequence is highly conserved. This suggests an important regulatory role for this region mediated by this PTK. C1 NIAMS,BETHESDA,MD 20892. OI Rider, Lisa/0000-0002-6912-2458 NR 18 TC 7 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JAN 28 PY 1994 VL 138 IS 1-2 BP 219 EP 222 DI 10.1016/0378-1119(94)90811-7 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA NA661 UT WOS:A1994NA66100036 PM 8125304 ER PT J AU LI, WQ MISCHAK, H YU, JC WANG, LM MUSHINSKI, JF HEIDARAN, MA PIERCE, JH AF LI, WQ MISCHAK, H YU, JC WANG, LM MUSHINSKI, JF HEIDARAN, MA PIERCE, JH TI TYROSINE PHOSPHORYLATION OF PROTEIN-KINASE C-DELTA IN RESPONSE TO ITS ACTIVATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID TRANSFORM FIBROBLASTS; SIGNAL TRANSDUCTION; MAP KINASES; RECEPTOR; CELLS; STIMULATION; PATHWAYS; ALPHA; CDNA; IL-3 AB Retroviral vectors containing five different protein kinase C (PKC) isoenzymes (alpha, delta, epsilon, eta, xeta) were expressed in 32D hematopoietic cells and NIH-3T3 fibroblasts. In an effort to investigate signaling events regulated by PKC activation, we analyzed whether tyrosine phosphorylation of cellular proteins would occur after 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment of the various transfectants. While no detectable tyrosine-specific phosphorylation was observed after treatment of the majority of the transfectants, pronounced TPA-dependent tyrosine phosphorylation of an 82-kDa protein was detected in the 32D/PKC-delta and NIH-3T3/PKC-delta lines. Interestingly, the 82-kDa substrate proved to be PKC-delta itself. Tyrosine phosphorylation of purified PKC-delta by src family or receptor tyrosine kinases in vitro enhanced PKC-delta activity, suggesting that tyrosine phosphorylation of PKC-delta may positively affect its function. C1 NCI,MOLEC GENET SECT,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NCI,MOLEC GENET SECT,GENET LAB,BETHESDA,MD 20892. RI Mischak, Harald/E-8685-2011 NR 26 TC 172 Z9 174 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 28 PY 1994 VL 269 IS 4 BP 2349 EP 2352 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MV432 UT WOS:A1994MV43200001 PM 7507923 ER PT J AU TAKEDA, A MAIZEL, AL KITAMURA, K OHTA, T KIMURA, S AF TAKEDA, A MAIZEL, AL KITAMURA, K OHTA, T KIMURA, S TI MOLECULAR-CLONING OF THE CD45-ASSOCIATED 30-KDA PROTEIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID CD45 PHOSPHOTYROSINE PHOSPHATASE; CELL ANTIGEN RECEPTOR; TYROSINE PHOSPHATASE; SIGNAL TRANSDUCTION; T-CELLS; KINASE; ACTIVATION; PHOSPHORYLATION; EXPRESSION; ANTIBODIES AB CD45, a leukocyte-specific transmembrane protein tyrosine phosphatase, mediates signal transduction pathways critical for immune responses. However, the mechanism of CD45-mediated signal transduction and the identity of CD45-associated proteins have remained unclear. A CD45-associated 30-kDa phosphorylated protein (CD45-AP) was purified by virtue of its specific association with CD45, and its mouse cDNA was cloned by using the internal amino acid sequence information. In vitro translated CD45-AP bound specifically to CD45. CD45-AP appears to be leukocyte-specific and shares no significant homology with presently known sequences. The predicted sequence contains no consensus tyrosine phosphorylation sites or conserved sequences of GTP-binding proteins. CD45-AP may act as an adapter molecule for CD45-mediated signal transduction. C1 NCI, MOLEC CARCINOGENESIS LAB, BETHESDA, MD 20892 USA. RP BROWN UNIV, ROGER WILLIAMS, MED CTR, DEPT PATHOL, 825 CHALKSTONE AVE, PROVIDENCE, RI 02908 USA. FU NCI NIH HHS [CA 45148, P30 CA13943] NR 32 TC 39 Z9 42 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 28 PY 1994 VL 269 IS 4 BP 2357 EP 2360 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MV432 UT WOS:A1994MV43200003 PM 8300558 ER PT J AU LEE, SW ELLIS, V DICHEK, DA AF LEE, SW ELLIS, V DICHEK, DA TI CHARACTERIZATION OF PLASMINOGEN ACTIVATION BY GLYCOSYLPHOSPHATIDYLINOSITOL-ANCHORED UROKINASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SINGLE-CHAIN UROKINASE; RECEPTOR-BOUND UROKINASE; HUMAN-ENDOTHELIAL-CELLS; PRO-UROKINASE; GLYCOSYL-PHOSPHATIDYLINOSITOL; ENZYMATIC-ACTIVITY; MEMBRANE; BINDING; MONOCYTES; KINETICS AB The characteristics of plasminogen activation by glycosylphosphatidylinositol (GPI)-anchored urokinase were evaluated and compared with those reported previously for receptor-bound urokinase. When expressed in cultured bovine aortic endothelial cells, GPI anchoring of single-chain urokinase plasminogen activator (scu-PA) potentiated plasmin generation as compared with GPI-anchored scu-PA that had been released into solution from the cell surface by enzymatic cleavage of the GPI anchor (''released'' scu-PA). The potentiation of plasmin generation by GPI-anchored scu-PA was inhibited in a dose-dependent manner by 6-aminohexanoic acid, a lysine analog, suggesting that the augmentation of plasmin generation by GPI-anchored scu-PA was dependent on simultaneous binding of plasminogen to the cell surface. GPI-anchored two-chain urokinase (tcu)-PA cleaved a peptide substrate at a rate equivalent to that of released urokinase. However, at a plasminogen concentration of 0.5 muM, GPI-anchored tcu-PA activated plasminogen less rapidly than did released urokinase. Modeling of kinetics of individual reactions revealed that cell-associated plasminogen activation by GPI-anchored tcu-PA was characterized by a K(m) of approximately 0.15 muM. This value of K(m) was 70-fold below that for activation of solution plasminogen by GPI-anchored urokinase. There was a concomitant decrease in V(max) for plasminogen activation by anchored tcu-PA. These alterations in kinetic parameters are similar to those reported previously for the activation of plasminogen by receptor-bound tcu-PA. In addition, GPI-anchored tcu-PA exhibited a modest resistance to plasminogen activator inhibitor 1 inactivation. The enzymatic characteristics of GPI-anchored urokinase reported here resemble closely those reported previously for receptor-bound urokinase. These data suggest that the urokinase receptor may regulate plasmin generation through a relatively nonspecific localization of urokinase to the cell Surface rather than through any intrinsic property of the urokinase receptor. C1 NHLBI,MOLEC HEMATOL BRANCH,BLDG 10,RM 7D-18,BETHESDA,MD 20892. RIGSHOSP,FINSEN LAB,DK-2100 COPENHAGEN,DENMARK. RI Ellis, Vincent/D-1860-2009 OI Ellis, Vincent/0000-0003-1956-073X NR 31 TC 35 Z9 35 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 28 PY 1994 VL 269 IS 4 BP 2411 EP 2418 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MV432 UT WOS:A1994MV43200014 PM 8300567 ER PT J AU DECOSTA, BR GEORGE, C LI, GY HE, XS AF DECOSTA, BR GEORGE, C LI, GY HE, XS TI HIGH-YIELD TRIFLUOROACETIC ACID-MEDIATED INTERMOLECULAR CONDENSATION OF 1-[2-BENZO[B]THIENYL]CYCLOALKANOLS SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Note ID DOPAMINE C1 NIDDKD,ANALYT CHEM LAB,BETHESDA,MD 20892. USN,RES LAB,STRUCT MATTER LAB,WASHINGTON,DC 20375. RP DECOSTA, BR (reprint author), NIDDKD,MED CHEM LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 9 TC 3 Z9 3 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD JAN 28 PY 1994 VL 59 IS 2 BP 482 EP 485 DI 10.1021/jo00081a033 PG 4 WC Chemistry, Organic SC Chemistry GA MV010 UT WOS:A1994MV01000033 ER PT J AU WU, TC LICHTEN, M AF WU, TC LICHTEN, M TI MEIOSIS-INDUCED DOUBLE-STRAND BREAK SITES DETERMINED BY YEAST CHROMATIN STRUCTURE SO SCIENCE LA English DT Article ID MEIOTIC GENE CONVERSION; SYNAPTONEMAL COMPLEX-FORMATION; RECOMBINATION INITIATION SITE; SACCHAROMYCES-CEREVISIAE; CHROMOSOME-III; ARG4 LOCUS; DNA; PROMOTER; SEQUENCE; MAP AB Double-strand DNA breaks (DSBs) occur at recombination hotspots during Saccharomyces cerevisiae meiosis and are thought to initiate exchange at these loci. Analysis of DSB sites in three regions of the yeast genome indicated that breaks occur at or near many potential transcription promoters and that DSBs initiate most, if not all, meiotic recombination. DSB sites displayed deoxyribonuclease I hypersensitivity in chromatin from mitotic and meiotic cells, and changes in chromatin structure produced parallel changes in the occurrence of DSBs. Thus, features of chromatin structure that are established before meiosis play a role in determining where meiotic recombination events initiate. C1 NCI,DIV CANC BIOL DIAGN & CTR,BIOCHEM LAB,BLDG 37,ROOM 4D14,BETHESDA,MD 20892. RI Lichten, Michael/C-5795-2013 OI Lichten, Michael/0000-0001-9707-2956 NR 42 TC 346 Z9 353 U1 0 U2 6 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JAN 28 PY 1994 VL 263 IS 5146 BP 515 EP 518 DI 10.1126/science.8290959 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MT966 UT WOS:A1994MT96600031 PM 8290959 ER PT J AU MILLER, EK DESIMONE, R AF MILLER, EK DESIMONE, R TI PARALLEL NEURONAL MECHANISMS FOR SHORT-TERM-MEMORY SO SCIENCE LA English DT Article ID INFERIOR TEMPORAL CORTEX; HIPPOCAMPAL-FORMATION; RECOGNITION MEMORY; MONKEYS; TASKS AB Although objects that have just been seen may persist in memory automatically for a time and interact passively with incoming stimulation, some tasks require that the memory be actively maintained and used. To test for the existence of separate automatic and volitional mechanisms of short-term memory, recordings were made from neurons in the inferior temporal cortex of monkeys while the monkeys held a sample picture ''in mind'' and signaled when it was repeated in a sequence of pictures, ignoring other stimulus repetitions. Some neurons were suppressed by any picture repetition, regardless of relevance, whereas others were enhanced, but only when a picture matched the sample. Short-term memory appears to reflect the parallel operation of these two mechanisms-one being automatic and the other active. RP MILLER, EK (reprint author), NIMH,NEUROPSYCHOL LAB,BLDG 49,ROOM 1B80,BETHESDA,MD 20892, USA. NR 16 TC 384 Z9 386 U1 0 U2 5 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JAN 28 PY 1994 VL 263 IS 5146 BP 520 EP 522 DI 10.1126/science.8290960 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MT966 UT WOS:A1994MT96600033 PM 8290960 ER PT J AU GRONENBORN, AM CLORE, GM AF GRONENBORN, AM CLORE, GM TI EXPERIMENTAL SUPPORT FOR THE HYDROPHOBIC ZIPPER HYPOTHESIS SO SCIENCE LA English DT Article RP GRONENBORN, AM (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 4 TC 33 Z9 34 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JAN 28 PY 1994 VL 263 IS 5146 BP 536 EP 536 DI 10.1126/science.8290964 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MT966 UT WOS:A1994MT96600038 PM 8290964 ER PT J AU OIE, T TOPOL, IA BURT, SK AF OIE, T TOPOL, IA BURT, SK TI AB-INITIO AND DENSITY-FUNCTIONAL CALCULATIONS ON ETHYLENE-GLYCOL SO JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article ID CONFORMATIONAL-ANALYSIS; ABINITIO CALCULATIONS; MOLECULAR GEOMETRIES; MICROWAVE-SPECTRUM; INTERNAL-ROTATION; GAS-PHASE; ENERGIES; 1,2-DIFLUOROETHANE; EQUILIBRIUM; 1,2-DIMETHOXYETHANE AB A comparative study between a high-level ab initio molecular orbital methods and density functional theory (DFT) employing local and nonlocal density approximations has been performed on 10 equilibrium conformers of ethylene glycol. These 10 structures are separated by relatively small energy differences with the two lowest energy structures forming intramolecular hydrogen bonds. All 10 conformers were optimized, by both methods, using comparable basis sets (double-zeta plus polarization in valence orbitals) including correlation effects, followed by even larger basis set single-point energy calculations. The optimized geometries and the relative energies calculated by the DFT method, when nonlocal and gradient corrections to the exchange-correlation potential (NLGC) were included, are found to be in good agreement with the ab initio results. The effects of the NLGC on the geometries and relative energies with special attentions to hydrogen bonding and the gauche effect are discussed. C1 NATL CANC INST,FREDERICK CANC RES & DEV CTR,PRI DYN CORP,FREDERICK BIOMED SUPERCOMP CTR,FREDERICK,MD 21702. ABBOTT LABS,DIV PHARMACEUT PROD,ABBOTT PK,IL 60064. NR 51 TC 61 Z9 61 U1 2 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3654 J9 J PHYS CHEM-US JI J. Phys. Chem. PD JAN 27 PY 1994 VL 98 IS 4 BP 1121 EP 1128 DI 10.1021/j100055a013 PG 8 WC Chemistry, Physical SC Chemistry GA MU060 UT WOS:A1994MU06000013 ER PT J AU HAVERKOS, H NEEDLE, R AF HAVERKOS, H NEEDLE, R TI REPORTING AIDS IN NEW-YORK-CITY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP HAVERKOS, H (reprint author), NIDA,ROCKVILLE,MD, USA. NR 3 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 JAN 26 PY 1994 VL 271 IS 4 BP 273 EP 274 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA MR221 UT WOS:A1994MR22100019 PM 8295284 ER PT J AU NUSSENBLATT, RB BELFORT, R AF NUSSENBLATT, RB BELFORT, R TI OCULAR TOXOPLASMOSIS - AN OLD DISEASE REVISITED SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Discussion ID GONDII; MANAGEMENT; ANTIGEN; PATIENT C1 HOSP SAO PAULO,ESCOLA PAULISTA MED,DEPT OPHTHALMOL,SAO PAULO,BRAZIL. RP NUSSENBLATT, RB (reprint author), NEI,IMMUNOL LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Belfort Jr, Rubens/E-2252-2012 OI Belfort Jr, Rubens/0000-0002-8422-3898 NR 26 TC 56 Z9 57 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 26 PY 1994 VL 271 IS 4 BP 304 EP 307 DI 10.1001/jama.271.4.304 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA MR221 UT WOS:A1994MR22100028 PM 8295291 ER PT J AU WEISZ, A SCHER, AL SHINOMIYA, K FALES, HM ITO, Y AF WEISZ, A SCHER, AL SHINOMIYA, K FALES, HM ITO, Y TI A NEW PREPARATIVE-SCALE PURIFICATION TECHNIQUE - PH-ZONE-REFINING COUNTERCURRENT CHROMATOGRAPHY SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID DISPLACEMENT CHROMATOGRAPHY AB A novel countercurrent chromatographic technique is described for the preparative separation-with excellent resolution-of up to multigram quantities of organic acids. This separation is accomplished by addition of a simple acid (e.g., trifluoroacetic acid) to the sample solution or stationary phase, followed by isocratic elution with a basic mobile phase. The acids elute as well-resolved rectangularly shaped peaks. This technique should rind widespread application in any organic chemistry laboratory for the separation of crude mixtures and for the purification of isolated acids. C1 NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. US FDA,OFF COSMET & COLORS,WASHINGTON,DC 20204. NR 12 TC 100 Z9 101 U1 2 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JAN 26 PY 1994 VL 116 IS 2 BP 704 EP 708 DI 10.1021/ja00081a035 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA MV283 UT WOS:A1994MV28300035 ER PT J AU HARMON, PA HENDLER, RW LEVIN, IW AF HARMON, PA HENDLER, RW LEVIN, IW TI RESONANCE RAMAN AND OPTICAL SPECTROSCOPIC MONITORING OF HEME-A REDOX STATES IN CYTOCHROME-C-OXIDASE DURING POTENTIOMETRIC TITRATIONS SO BIOCHEMISTRY LA English DT Article ID SPECTRAL ISOLATION; REDUCTION; SITE; COOPERATIVITY; INVOLVEMENT; TRANSITION; OXIDATION AB Resonance Raman spectroscopy is used to monitor the redox state of heme a and heme a3 centers in cyanide-inhibited and native cytochrome oxidase during potentiometric titrations. Specific vibrational modes are resolved for each reduced heme with 441.6-nm excitation while oxidized species show vanishingly small Raman intensities. The voltage dependencies of the Raman intensities of reduced heme a and reduced heme a3 modes are quantitatively measured and used to extract heme a and a3 midpoint potentials. In the cyanide-bound enzyme, in which heme a3 remains in the oxidized state, the Raman data indicate that heme a centers exhibit complex Nernstian behavior with two E(m) values near 350 and 260 mV. In the native enzyme, this resonance Raman-potentiometric method reveals significantly different redox behavior for the two hemes. Heme a centers are described by two effective E(m) values near 350 and 220 mV, while heme a3 centers have lower E(m) values near 260 and 200 mV. Singular value decomposition analysis of optical spectral changes supports the Raman data. These results are in contrast to models of cytochrome oxidase redox behavior in which heme a and heme a3 are thought to have essentially identical midpoint potentials. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. NR 41 TC 10 Z9 10 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 25 PY 1994 VL 33 IS 3 BP 699 EP 707 DI 10.1021/bi00169a011 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MT700 UT WOS:A1994MT70000011 PM 8292597 ER PT J AU MAHADEVAN, D THANKI, N MCPHIE, P BEELER, JF YU, JC WLODAWER, A HEIDARAN, MA AF MAHADEVAN, D THANKI, N MCPHIE, P BEELER, JF YU, JC WLODAWER, A HEIDARAN, MA TI COMPARISON OF CALCIUM-DEPENDENT CONFORMATIONAL-CHANGES IN THE N-TERMINAL SH2-DOMAINS OF P85 AND GAP DEFINES DISTINCT PROPERTIES FOR SH2-DOMAINS SO BIOCHEMISTRY LA English DT Article ID FACTOR-I RECEPTOR; GTPASE-ACTIVATING PROTEIN; MANNOSE-BINDING PROTEIN; GROWTH-FACTOR RECEPTORS; SIGNAL TRANSDUCTION; PHOSPHATIDYLINOSITOL 3-KINASE; PDGF RECEPTOR; STRUCTURAL FEATURES; RECOGNITION DOMAIN; P85-ALPHA SUBUNIT AB Src-homology region 2 (SH2) domains are stretches of about 100 amino acids which are found to be structurally conserved in a number of signaling molecules. These regions have been shown to bind with high affinity to phosphotyrosine residues within activated receptor tyrosine kinases. Here we report the bacterial expression and purification of individual N-terminal SH2 (NSH2) domains of phosphatidylinositol 3-kinase (PI-3K) binding subunit (p85) and Ras GTPase activating protein (GAP) in amounts suitable for structure-function studies. The p85NSH2 domain stains dark purple and absorbs around 620-640 nm with Stains-all, a dye known to bind to calcium binding proteins. This effect was not observed for the GAPNSH2 domain. Circular dichroism analysis of the N-terminal SH2 domain of these proteins shows that p85NSH2, but not GAPNSH2, undergoes a significant dose-dependent change in conformation in the presence of increasing calcium concentrations. Moreover, the conformational change of p85NSH2 induced by calcium could be replicated by addition of a phosphorylated hexapeptide (DYpMDMK) representing the alpha-PDGFR binding site for p85. Limited proteolysis studies showed a significant calcium-dependent increase in protection of p85NSH2 but not GAPNSH2 from degradation by subtilisin. Our results further indicate that holmium, a trivalent lanthanide ion, which has been previously shown to substitute for calcium, could also protect the p85NSH2 domain from proteolysis even at 10-fold Iower concentrations. In vitro binding studies using purified preparations of activated alpha-PDGFR show that calcium did not affect the binding of GAPNSH2 domains to activated alpha-PDGFR. In striking contrast, we observed a marked increase in binding of p85NSH2 domains to activated alpha-PDGFR in the presence of calcium ions. Sequence comparisons and molecular modeling of the p85NSH2 domain based on the v-Src SH2 domain structure show a conserved arrangement of oxygen ligands contributing to two potential calcium binding sites within the p85NSH2 domain. These have been rationalized to be surface loop regions, i.e., loops 2 and 4 and loops 6, 7, and 8, close to the N- and C-terminal alpha-helical regions, respectively. Together, our findings suggest that the conformation of p85NSH2, but not that of GAPNSH2, is modulated by the presence of calcium ions. This implies that calcium ions may regulate PI-3K (p85alpha) binding to alpha-PDGFR in vivo and suggests that the NSH2 domains of p85 and GAP may have distinct functions in receptor-mediated signal transduction. C1 NCI FCRDC,MACROMOLEC STRUCT LAB,ABL BASIC RES PROGRAM,POB B,FREDERICK,MD 21702. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NCI,BIOCHEM & METAB LAB,BETHESDA,MD 20892. FU NCI NIH HHS [N01-CO-74101] NR 45 TC 20 Z9 20 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 25 PY 1994 VL 33 IS 3 BP 746 EP 754 DI 10.1021/bi00169a016 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MT700 UT WOS:A1994MT70000016 PM 8292602 ER PT J AU PAPP, PP CHATTORAJ, DK AF PAPP, PP CHATTORAJ, DK TI MISSING-BASE AND ETHYLATION INTERFERENCE FOOTPRINTING OF P1 PLASMID REPLICATION INITIATOR SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PROTEIN AB RepA, the replication initiator protein of plasmid P1, binds to specific 19 bp sequences on the plasmid DNA. Earlier footprinting studies with dimethylsulfate identified the guanines that contact RepA through the major groove of DNA. In this study, base elimination was used to identify the contribution of all four bases to the binding reaction. Depurination and depyrimidation of any base in the neighborhood of the contacting guanines was found to decrease RepA binding. These results are consistent with the notion that RepA contacts bases of two consecutive major grooves on the same face of DNA. We also observed that depurination but not methylation of three guanines (G3, G8 and G9) affected binding. We identified the DNA phosphate groups (3 in the top strand, one of which mapped between G8 and G9, and 4 in the bottom strand, one of which was adjacent to C3) that strongly interfered with RepA binding upon ethylation. These results indicate that certain bases (e.g. G3, G8 and G9) may not contact RepA directly but contribute to base and backbone contacts by maintaining proper structure of the binding site. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. RI Papp, Peter/A-6907-2013 NR 14 TC 16 Z9 16 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 25 PY 1994 VL 22 IS 2 BP 152 EP 157 DI 10.1093/nar/22.2.152 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MV140 UT WOS:A1994MV14000006 PM 8121798 ER PT J AU SCHNITZLER, P HUG, M HANDERMANN, M JANSSEN, W KOONIN, EV DELIUS, H DARAI, G AF SCHNITZLER, P HUG, M HANDERMANN, M JANSSEN, W KOONIN, EV DELIUS, H DARAI, G TI IDENTIFICATION OF GENES ENCODING ZINC-FINGER PROTEINS, NONHISTONE CHROMOSOMAL HMG PROTEIN HOMOLOG, AND A PUTATIVE GTP PHOSPHOHYDROLASE IN THE GENOME OF CHILO IRIDESCENT VIRUS SO NUCLEIC ACIDS RESEARCH LA English DT Article ID NUCLEAR POLYHEDROSIS-VIRUS; REPETITIVE DNA ELEMENTS; MOLECULAR-CLONING; CIRCULAR PERMUTATION; NUCLEOTIDE-SEQUENCE; GEL-ELECTROPHORESIS; VACCINIA VIRUS; TYPE-6; REPLICATION; RNA AB Five RNA transcripts of about 1.2 to 1.7 kilobases were mapped to a part of the genome of insect iridescent virus type 6 (Chile iridescent virus; CIV) between genome coordinates 0.832 and 0.856 within the EcoRI DNA fragment F. The nucleotide sequence of this particular region (5702 base pairs) of the CIV genome was determined. The DNA sequence contains a number of perfect direct, inverted, and palindromic repeats including three clusters of tandemly organized repetitive DNA elements located between the nucleotide positions 1534 to 1566, 3720 to 3780, and 4350 to 4450. Eight long open reading frames (ORFs; EF1 to 8) were detected in the sequenced region of the CIV genome. ORF EF1 encodes a putative protein of 221 amino acid residues (aa) that is closely related to eukaryotic nonhistone chromosomal proteins of the high mobility group (HMG) superfamily. Virus encoded homologues of HMG proteins have not been reported so far. The EF2 gene product (145 aa) contains a specific zinc finger motif and belongs to a distinct group of identified and putative zinc finger proteins including a second putative protein (239 aa) of CIV encoded in the EcoRI DNA fragment Y (1984 bp; 0.381 to 0.391 viral map units). The product of EF6 (127 aa) is related to D250 ORF product of African swine fever virus (ASFV) and belongs to the recently described protein family sharing a highly conserved sequence motif with bacterial antimutator GTP phosphohydrolase MutT. Thus the sequenced region of the CIV genome encodes three putative proteins which may be directly involved in the replication and/or transcription of the viral DNA. C1 UNIV HEIDELBERG, INST MED VIROL, D-69120 HEIDELBERG, GERMANY. NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20894 USA. DEUTSCH KREBSFORSCHUNGSZENTRUM, INST ANGEW TUMORVIROL, D-69120 HEIDELBERG, GERMANY. NR 73 TC 15 Z9 17 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 25 PY 1994 VL 22 IS 2 BP 158 EP 166 DI 10.1093/nar/22.2.158 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MV140 UT WOS:A1994MV14000007 PM 8121799 ER PT J AU CLUBB, RT OMICHINSKI, JG CLORE, GM GRONENBORN, AM AF CLUBB, RT OMICHINSKI, JG CLORE, GM GRONENBORN, AM TI MAPPING THE BINDING SURFACE OF INTERLEUKIN-8 COMPLEXED WITH AN N-TERMINAL FRAGMENT OF THE TYPE-1 HUMAN INTERLEUKIN-8 RECEPTOR SO FEBS LETTERS LA English DT Article DE INTERLEUKIN-8; INTERLEUKIN-8 RECEPTOR; PROTEIN NMR; CYTOKINE-RECEPTOR INTERACTION ID 3-DIMENSIONAL STRUCTURE; SPECTROSCOPY; NMR; PROTEINS; RESIDUES; SPECTRA AB Interleukin-8 and its receptors are key mediators of immune and inflammatory responses. Heteronuclear NMR spectroscopy has been utilized to map the binding surface on interleukin-8 (IL-8) for an N-terminal fragment of the human Type-1 IL-8 receptor. A peptide corresponding to residues 1-40 of the IL-8 type 1 receptor (IL8-rl) was titrated into a sample of uniformly N-15-labeled IL-8. IL8-rl binds to IL-8 with a dissociation constant of 170 +/- 50 mu M assuming the peptide binds with a stoichiometry of one peptide per IL-8 monomer, exchanges rapidly (> 900 s(-1)) between free and bound states, and selectively perturbs the chemical environment of several IL-8 residues. The binding surface on IL-8 suggested by our results is comprised of residues in strand beta 3 of the beta-sheet (Glu(48) to Cys(50)), the turn preceding beta 3 (ser(44)), the C-terminal alpha-helix (Val(61)) and the irregular N-terminal loop region (Thr(12), Lys(15), Phe(17), His(18), Lys(20) and Phe(21)). The IL-8 dimer appears to present two symmetrical binding surfaces for the IL8-rl peptide, suggesting two receptor peptides may bind per dimer. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 27 TC 77 Z9 79 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JAN 24 PY 1994 VL 338 IS 1 BP 93 EP 97 DI 10.1016/0014-5793(94)80123-1 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA MV393 UT WOS:A1994MV39300019 PM 8307164 ER PT J AU SMYTH, MS BURKE, TR AF SMYTH, MS BURKE, TR TI ENANTIOSELECTIVE SYNTHESIS OF N-BOC AND N-FMOC PROTECTED DIETHYL 4-PHOSPHONO(DIFLUOROMETHYL)-L-PHENYLALANINE - AGENTS SUITABLE FOR THE SOLID-PHASE SYNTHESIS OF PEPTIDES CONTAINING NONHYDROLYZABLE ANALOGS OF O-PHOSPHOTYROSINE SO TETRAHEDRON LETTERS LA English DT Article ID ACIDS AB Enantioselective convergent syntheses of N-Boc and N-Fmoc protected diethyl 4-phosphono(difluoromethyl)-L-phenylalanine are reported. le analogues of O-phosphotyrosine/ C1 NCI,DCT,DTP,MED CHEM LAB,BETHESDA,MD 20892. RI Burke, Terrence/N-2601-2014 NR 16 TC 88 Z9 88 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD JAN 24 PY 1994 VL 35 IS 4 BP 551 EP 554 DI 10.1016/S0040-4039(00)75835-7 PG 4 WC Chemistry, Organic SC Chemistry GA MR750 UT WOS:A1994MR75000013 ER PT J AU RANCE, NE YOUNG, WS MCMULLEN, NT AF RANCE, NE YOUNG, WS MCMULLEN, NT TI TOPOGRAPHY OF NEURONS EXPRESSING LUTEINIZING-HORMONE-RELEASING HORMONE GENE TRANSCRIPTS IN THE HUMAN HYPOTHALAMUS AND BASAL FOREBRAIN SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE GONADOTROPIN-RELEASING HORMONE; IN SITU HYBRIDIZATION; NUCLEUS BASALIS OF MEYNERT; AMYGDALA; PUTAMEN ID MESSENGER-RIBONUCLEIC-ACID; LHRH-IMMUNOREACTIVE NEURONS; SEXUALLY DIMORPHIC NUCLEUS; RHESUS-MONKEY; HUMAN-BRAIN; IMMUNOCYTOCHEMICAL LOCALIZATION; INSITU HYBRIDIZATION; FEMALE RAT; CHOLINERGIC INNERVATION; GONADOTROPIN-SECRETION AB The distribution of neurons expressing luteinizing hormone-releasing hormone (LHRH) gene transcripts was mapped in the human hypothalamus and basal forebrain by in situ hybridization and computer-assisted microscopy. Hypothalamic blocks were dissected from five adult males and one adult female and snap frozen in isopentane. The blocks were serially sectioned either in the coronal or in the sagittal plane at a thickness of 20 mu m. Approximately every twentieth section was incubated with a S-35-labeled cDNA probe complementary to LHRH mRNA. Specificity was confirmed by hybridization of adjacent sections with a probe targeted to the gonadotropin-associated protein (GAP) region of LHRH messenger ribonucleic acids (mRNA). Maps of neurons containing LHRH mRNA were manually digitized with the aid of an image-combining computer microscope system. We report a much wider distribution and greater numbers of LHRH neurons than have been previously described in the human brain. Three morphological subtypes were observed based on cell size and labeling density: 1) small, heavily labeled, oval or fusiform neurons, located primarily in the medial basal hypothalamus, ventral preoptic area, and periventricular zone; 2) small, oval, sparsely labeled neurons located in the septum and dorsal preoptic region and scattered from the bed nucleus of the stria terminalis to the amygdala (''extended amygdala''); and 3) large round neurons (>500 mu m(2) sectional profile area), intermediate in labeling density, scattered within the magnocellular basal forebrain complex, extended amygdala, ventral pallidum, and putamen. The pronounced differences in morphology, labeling density, and location of the three subtypes suggest that distinct functional subgroups of LHRH neurons exist in the human brain. C1 UNIV ARIZONA, COLL MED, DEPT ANAT, TUCSON, AZ 85724 USA. UNIV ARIZONA, COLL MED, DEPT NEUROL, TUCSON, AZ 85724 USA. NIMH, CELL BIOL LAB, BETHESDA, MD 20892 USA. RP UNIV ARIZONA, COLL MED, DEPT PATHOL, 1501 N CAMPBELL, TUCSON, AZ 85724 USA. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 FU NIA NIH HHS [AG-09214] NR 85 TC 50 Z9 50 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9967 EI 1096-9861 J9 J COMP NEUROL JI J. Comp. Neurol. PD JAN 22 PY 1994 VL 339 IS 4 BP 573 EP 586 DI 10.1002/cne.903390408 PG 14 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA MP506 UT WOS:A1994MP50600007 PM 8144747 ER PT J AU WIERTELAK, EP YANG, HYT MOONEYHEIBERGER, K MAIER, SF WATKINS, LR AF WIERTELAK, EP YANG, HYT MOONEYHEIBERGER, K MAIER, SF WATKINS, LR TI THE NATURE OF CONDITIONED ANTI-ANALGESIA - SPINAL-CORD OPIATE AND ANTI-OPIATE NEUROCHEMISTRY SO BRAIN RESEARCH LA English DT Article DE CHOLECYSTOSKININ; NEUROPEPTIDE FF; DYNORPHIN; MU OPIATE RECEPTOR; DELTA OPIATE RECEPTOR; SPINAL CORD; PAIN FACILITATION; CONDITIONED ANALGESIA; CONDITIONED ANTI-ANALGESIA ID STRESS-INDUCED ANALGESIA; SHOCK INDUCED ANTINOCICEPTION; FOOTSHOCK-INDUCED ANALGESIA; OPIOID RECEPTOR ANTAGONIST; PAIN CONTROL-SYSTEMS; MORPHINE-TOLERANCE; BETA-ENDORPHIN; CHOLECYSTOKININ; RAT; NEUROPEPTIDE AB The central nervous system contains circuitry that inhibits pain sensitivity (analgesia), as well as circuitry that opposes pain inhibition (anti-analgesia). Activation of analgesia systems and anti-analgesia systems can each be brought under environmental control using classical conditioning procedures. Analgesia can be produced by cues present before and during aversive events such as electric shock, while active inhibition of analgesia comes to be produced by cues never present immediately before or during shock and therefore signal safety. We have recently reported that these analgesia and anti-analgesia systems interact at the level of the spinal cord. A series of 3 experiments were performed to examine how such interactions occur. First, potential opioid mediation of conditioned analgesia was investigated using systemic and intrathecal (i.t.) delivery of opiate antagonists. Conditioned analgesia was found to be mediated by activation of spinal mu and delta opiate receptors. Second, analgesia produced by each of these receptor subtypes was challenged by environmental signals for safety. Analgesias produced by mu and delta opiate agonists were each abolished by safety signals. Third, antagonists/antisera directed against several putative anti-opiate neurotransmitters were tested i.t. to identify which mediate conditioned anti-analgesia at the level of the spinal cord. A cholecystokinin antagonist abolished conditioned anti-analgesia. In contrast, neuropeptide FF antiserum and a kappa opiate antagonist were without effect. C1 UNIV COLORADO,DEPT PSYCHOL,BOULDER,CO 80309. MACALESTER COLL,DEPT PSYCHOL,ST PAUL,MN 55105. NIMH,WASHINGTON,DC 20032. NR 63 TC 33 Z9 34 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 21 PY 1994 VL 634 IS 2 BP 214 EP 226 DI 10.1016/0006-8993(94)91924-0 PG 13 WC Neurosciences SC Neurosciences & Neurology GA MR359 UT WOS:A1994MR35900004 PM 8131071 ER PT J AU YIM, MB CHAE, HZ RHEE, SG CHOCK, PB STADTMAN, ER AF YIM, MB CHAE, HZ RHEE, SG CHOCK, PB STADTMAN, ER TI ON THE PROTECTIVE MECHANISM OF THE THIOL-SPECIFIC ANTIOXIDANT ENZYME AGAINST THE OXIDATIVE DAMAGE OF BIOMACROMOLECULES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ELECTRON-SPIN RESONANCE; PULSE-RADIOLYSIS; THIYL RADICALS; LIPID-PEROXIDATION; HYDROGEN-PEROXIDE; MOLECULAR-OXYGEN; AQUEOUS-SOLUTION; GLUTATHIONE; DITHIOTHREITOL; INACTIVATION AB A thiol-specific antioxidant enzyme (TSA), which provides protection against the inactivation of other enzymes by the thiol/Fe(III)/oxygen system, was previously isolated and cloned. We investigated the mechanism by which TSA protects biomolecules from oxidative damage caused by the thiol-containing oxidation system using the spin trapping method with 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Thiyl radicals from dithiothreitol (.DTT) were produced by horseradish peroxidase/H2O2 under aerobic and anaerobic conditions and by the Fe(III)/oxygen system. The formation of DMPO-.DTT radical adducts were inhibited by TSA regardless of the thiyl radical-generating conditions used. The active mutant C170S also quenched the signals of the radical adduct, whereas the inactive mutant C47S did not exert any effect. It was also found that C170S has a higher rate at the initial stage of the reaction than that of the native enzyme, although C170S failed to remove DMPO-.DTT radical adducts completely. These results indicate that only active TSA can catalyze the removal of thiyl radicals, and cysteine 47 is required for this activity. In addition, thiyl radicals react with oxygen to generate unidentified thiylperoxy species. Fe.EDTA reacts with this species to generate a reactive radical that can abstract hydrogen atom from ethanol to produce a hydroxyethyl radical. This reactive thiyl-oxygen radical is believed to be responsible for causing deleterious effects on biomolecules. Together, our data indicate that TSA protects biomolecules from oxidative damage by catalyzing the removal of thiyl radicals before they generate more reactive radicals. However, presently we cannot rule out the possibility that TSA can also use other thiol-containing species as substrates. RP YIM, MB (reprint author), NHLBI,BIOCHEM LAB,BLDG 3,RM 202,BETHESDA,MD 20892, USA. NR 46 TC 101 Z9 101 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 21 PY 1994 VL 269 IS 3 BP 1621 EP 1626 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR988 UT WOS:A1994MR98800015 PM 8294408 ER PT J AU ROBERTS, JD IZUTA, S THOMAS, DC KUNKEL, TA AF ROBERTS, JD IZUTA, S THOMAS, DC KUNKEL, TA TI MISPAIR-SPECIFIC, SITE-SPECIFIC, AND STRAND-SPECIFIC ERROR RATES DURING SIMIAN VIRUS-40 ORIGIN-DEPENDENT REPLICATION IN-VITRO WITH EXCESS DEOXYTHYMIDINE TRIPHOSPHATE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SV40 DNA-REPLICATION; INITIATION; FIDELITY; EXTRACTS; REPAIR AB We have measured the fidelity of leading and lagging strand DNA replication in HeLa cell extracts. Providing an excess of one dNTP in reactions induces replication errors consistent with misincorporation of that dNTP. With excess dTTP, both substitutions and single-nucleotide frameshifts are induced. Error distribution is nonrandom; reproducible hot spots for a substitution and a frameshift error are observed. Measurements with two vectors having the origin of replication on opposite sides of the mutational target demonstrate that error rates for G.dTTP and C.dTTP mispairs depend on whether the strand is replicated as the leading or lagging strand. Also, the two hot spots are only observed in one origin-target orientation. Replication reactions reconstituted from two fractions derived from extracts are 3-fold less accurate, but the error specificity with excess dTTP is similar to that with extracts. This suggests that the processes responsible for the nonrandom error rates are not lost as a result of fractionation. Furthermore, the reconstituted system is devoid of mismatch repair activity. Thus, mismatch repair is not responsible for the mispair-, site-, and strand-specific differences observed. C1 NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. NR 23 TC 33 Z9 33 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 21 PY 1994 VL 269 IS 3 BP 1711 EP 1717 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR988 UT WOS:A1994MR98800029 PM 8294419 ER PT J AU JOUNEAUX, C MALLAT, A SERRADEILLEGAL, C GOLDSMITH, P HANOUNE, J LOTERSZTAJN, S AF JOUNEAUX, C MALLAT, A SERRADEILLEGAL, C GOLDSMITH, P HANOUNE, J LOTERSZTAJN, S TI COUPLING OF ENDOTHELIN B-RECEPTORS TO THE CALCIUM-PUMP AND PHOSPHOLIPASE-C VIA GS AND GQ IN RAT-LIVER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BINDING REGULATORY PROTEIN; BETA-GAMMA-SUBUNITS; SIGNAL TRANSDUCTION; GUANINE-NUCLEOTIDE; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; PLASMA-MEMBRANES; ADENYLYL CYCLASE; ALPHA-SUBUNITS; CA-2+ PUMP; ACTIVATION AB We have demonstrated in liver from male rats that both endothelin A (ET(A)) and ET(B) receptors coexist in equal proportion and that ET(A) receptors mediate a calcium-dependent activation of glycogenolysis. We describe here a sex difference in endothelin action in hepatocytes because, in female rats, 80% of the ET receptors are of ET(B) type and, accordingly, activation of glycogenolysis is an ET(B)-mediated process (EC50 = 0.03 pm). ET- 1 stimulation of glycogenolysis in female rats was consecutive to activation of phosphatidylinositol 4,5-bisphosphate hydrolysis (EC50 = 0.03 pm) and to inhibition of the calcium extrusion pump (IC50 = 0.03 pm) in plasma membranes, with ET-1 almost-equal-to sarafotoxin S6C almost-equal-to ET-3. Endothelin regulation of each effector was potentiated by GTPgammaS. ET-1 did not stimulate adenylyl cyclase activity. To identify the nature of the guanine nucleotide regulatory proteins (G protein(s)) coupling ET(B) receptors to each effector, we used antibodies against the COOH terminus of different G protein alpha subunits. Antibodies reactive with Gsalpha (RM) blocked ET-1 inhibition of the calcium pump, while they did not affect ET-1 stimulation of phospholipase C. Antibodies reactive with Gqalpha (QL) dose-dependently antagonized stimulation of phospholipase C by ET-1 and vasopressin, without affecting ET-1 inhibition of the calcium pump. Antibodies reactive with Gi1alpha/Gi2alpha (AS) had no effect on either system. We conclude that the calcium signal provoked by endothelins in hepatocyte is not only consecutive to activation of phospholipase C but also to inhibition of the plasma membrane calcium pump, each effector being coupled to ET(B) receptors by different G proteins, Gq, and Gs. C1 SANOFI RECH,BIOCHIM EXPLORATOIRE,F-31036 TOULOUSE,FRANCE. NIDDKD,MOLEC PATHOPHYSIOL BRANCH,BETHESDA,MD 20892. RP JOUNEAUX, C (reprint author), HOP HENRI MONDOR,INSERM,U99,F-94010 CRETEIL,FRANCE. NR 43 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 JAN 21 PY 1994 VL 269 IS 3 BP 1845 EP 1851 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR988 UT WOS:A1994MR98800047 PM 8294432 ER PT J AU SAUNDERS, NA JETTEN, AM AF SAUNDERS, NA JETTEN, AM TI CONTROL OF GROWTH-REGULATORY AND DIFFERENTIATION-SPECIFIC GENES IN HUMAN EPIDERMAL-KERATINOCYTES BY INTERFERON-GAMMA - ANTAGONISM BY RETINOIC ACID AND TRANSFORMING GROWTH-FACTOR-BETA-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CROSS-LINKED ENVELOPE; NECROSIS-FACTOR-ALPHA; CORNIFIED ENVELOPE; BINDING-PROTEIN; CELLS; TRANSGLUTAMINASE; EXPRESSION; ACTIVATION; INDUCTION; RECEPTOR AB Interferon gamma (IFN-gamma) is a potent inducer of squamous differentiation in normal human epidermal keratinocytes. This induction is characterized by a greater-than-or-equal-to 95% decrease in the mRNA level of two growth regulatory genes, cdc2 and E2F-1, and a 7-15-fold increase in the expression of two squamous cell-specific genes, transglutaminase type I and cornifin. In contrast to the decrease in cdc2 and E2F-1 expression, the increase in transglutaminase type I and cornifin mRNAs by IFN-gamma occurs after a lagtime of more than 12 h. These results are consistent with the hypothesis that in normal human epidermal keratinocyte cells irreversible growth arrest precedes the expression of the squamous-differentiated phenotype. The action of IFN-gamma on the expression of squamous cell-specific genes is antagonized by retinoic acid and transforming growth factor beta1. Both factors are potent suppressors of the induction of transglutaminase type I and, cornifin; however, they do not prevent the commitment to irreversible growth arrest. Several squamous cell carcinoma cell lines do not show a detectable decrease in cdc2 or increase in transglutaminase type I mRNA levels after IFN-gamma treatment and appear to be altered in their control of squamous differentiation. RP SAUNDERS, NA (reprint author), NIEHS,PULM PATHOBIOL LAB,CELL BIOL SECT,RES TRIANGLE PK,NC 27709, USA. RI saunders, nicholas/E-1544-2014; McTaggart, Jill/G-4696-2010; OI saunders, nicholas/0000-0002-2478-3420; McTaggart, Jill/0000-0002-9000-8529; Jetten, Anton/0000-0003-0954-4445 NR 46 TC 134 Z9 134 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 21 PY 1994 VL 269 IS 3 BP 2016 EP 2022 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR988 UT WOS:A1994MR98800072 PM 7904998 ER PT J AU SZALLASI, Z SMITH, CB PETTIT, GR BLUMBERG, PM AF SZALLASI, Z SMITH, CB PETTIT, GR BLUMBERG, PM TI DIFFERENTIAL REGULATION OF PROTEIN-KINASE-C ISOZYMES BY BRYOSTATIN-1 AND PHORBOL 12-MYRISTATE 13-ACETATE IN NIH 3T3 FIBROBLASTS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOUSE EPIDERMAL-CELLS; CARCINOMA-CELLS; ESTER; BINDING; JUN; PHOSPHORYLATION; ACTIVATION; MODULATION; HL-60; AP-1 AB Bryostatin 1 and phorbol 12-myristate 13-acetate (PMA) are both potent activators of protein kinase C (PKC), although in many systems bryostatin 1 induces only a subset of the responses to PMA and blocks those which it does not induce. We report here that in NIH 3T3 fibroblasts PMA showed similar potencies for translocating PKC isozymes alpha, delta, and epsilon to the Triton X-100-soluble and -insoluble fractions and for the down-regulation of the three isozymes. Bryostatin 1 was slightly more potent than PMA for translocating PKCalpha and was more potent than PMA for down-regulating it. Bryostatin 1 was markedly more potent than PMA for translocating PKCdelta but showed a biphasic dose-response curve for down-regulating this isozyme. 1-10 nm bryostatin 1 down-regulated PKCdelta to a similar extent as PMA; lower (10-100 pm) or, unexpectedly, higher (100 nm to 1 muM) doses of bryostatin 1 caused either no or reduced down-regulation. Moreover, these high (100 nm to 1 muM) doses of bryostatin 1 inhibited the down-regulation of PKCdelta by 1 muM PMA when coapplied. Bryostatin 1 caused translocation of PKCepsilon with slightly higher potency than PKCdelta, but there was no protection of this isozyme at any of the doses examined. Bryostatin 1 induced a long-term increase in c-Jun level. The dose-response curve for bryostatin 1 was biphasic, with maximal induction at 1-10 nM bryostatin 1, coincident with the maximal down-regulation of PKCdelta. We conclude that bryostatin 1 showed substantially different regulation for PKCalpha, PKCdelta, and PKCepsilon, whereas PMA distinguished only weakly between these isozymes. C1 NCI,CELLULAR CARCINOGENESIS LAB,BETHESDA,MD 20892. ARIZONA STATE UNIV,CANC RES INST,TEMPE,AZ 85287. ARIZONA STATE UNIV,DEPT CHEM,TEMPE,AZ 85287. NR 27 TC 211 Z9 211 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 21 PY 1994 VL 269 IS 3 BP 2118 EP 2124 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR988 UT WOS:A1994MR98800086 PM 8294465 ER PT J AU ADACHI, Y PAVLAKIS, GN COPELAND, TD AF ADACHI, Y PAVLAKIS, GN COPELAND, TD TI IDENTIFICATION AND CHARACTERIZATION OF SET, A NUCLEAR PHOSPHOPROTEIN ENCODED BY THE TRANSLOCATION BREAK POINT IN ACUTE UNDIFFERENTIATED LEUKEMIA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VIRUS TYPE-I; HEMATOPOIETIC SYSTEM CELLS; FUSION MESSENGER-RNA; TRANSCRIPTION FACTOR; PROTEIN-KINASE; CDNA CLONE; RAR-ALPHA; GENE; PHOSPHORYLATION; ABL AB The translocation (6;9) in acute nonlymphocytic leukemia results in the formation of a dek-can fusion gene. In a case of acute undifferentiated leukemia, the oncogene can is fused to a different gene, named set, instead of dek and is assumed to be activated. Transcripts of set encode a putative SET protein with a predicted molecular mass of 32 kDa. We identified SET as a 39-kDa protein by immunoprecipitation with rabbit antiserum against each of three synthetic peptides predicted from the open reading frame of the set gene. We confirmed this identification of SET by protein sequencing. We also observed that SET is expressed ubiquitously in various hu an cell lines. SET is phosphorylated on serine residue(s) in cultured cells and is localized predominantly in nuclei. Although the function(s) of SET and SET-CAN is not known, we propose that SET plays a key role in the mechanism of leukemogenesis. in acute undifferentiated leukemia, perhaps by activating CAN in nuclei and stimulating the transformation potential of SET-CAN. This proposed role would therefore be similar to the roles observed for BCR and DEK of the chimeric oncoproteins BCR-ABL and DEK-CAN in acute myeloid leukemia and acute nonlymphocytic leukemia, respectively. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,PROT STRUCT GRP,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,HUMAN RETROVIRUS SECT,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 34 TC 123 Z9 129 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 21 PY 1994 VL 269 IS 3 BP 2258 EP 2262 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR988 UT WOS:A1994MR98800105 PM 8294483 ER PT J AU DECOSTA, BR HE, XS DOMINGUEZ, C CUTTS, J WILLIAMS, W BOWEN, WD AF DECOSTA, BR HE, XS DOMINGUEZ, C CUTTS, J WILLIAMS, W BOWEN, WD TI A NEW APPROACH TO THE DESIGN OF SIGMA-2-SELECTIVE LIGANDS - SYNTHESIS AND EVALUATION OF N-[2-(3,4-DICHLOROPHENYL)ETHYL]-N-METHYL-2(1-PYRROLIDINYL)ETHYLAMINE-REL ATED POLYAMINES AT SIGMA-1 AND SIGMA-2 RECEPTOR SUBTYPES SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID BINDING-SITES; ANALOGS; AGENTS; BRAIN; RAT; AFFINITY AB A series of polyamines based on the high affinity sigma receptor ligand N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (3) were developed and evaluated for their binding characteristics at sigma-1 and sigma-2 receptor subtypes. The data indicated that a considerable degree of structural variation is possible while still retaining nanomolar affinity at a receptors; As the structure of the polyamines was varied, their binding at sigma-1 and sigma-2 subtypes showed quite different and in some cases opposite trends, supporting the belief that these are pharmacologically distinct entities. Polyamines containing two nitrogen atoms showed optimal binding at both sigma-1 and sigma-2 receptor subtypes. Although additional nitrogen atoms resulted in decreased affinity at sigma-1 and sigma-2 subtypes, an increase in selectivity for sigma-2 subtypes was evident; the parent 3 showed greater selectivity for sigma-1 subtypes. Internitrogen spacings had a large effect on binding affinity and subtype selectivity. For example, the difference between N-[3-(1-pyrrolidinyl)propyl]-N'-(3,4-dichlorobenzyl)-N,N'-dimethylethylenediamine (8) [K-i = 29.9 nM at sigma-1 receptor and 18.3 nM at alpha-2 receptor] to N-[3-(1-pyrrolidinyl)propyl]-N'-(3,4-dichlorobenzyl)-N/N'-dimethylethylenedi- amine (10) [K-i = 1.49 nM at sigma-1 receptor and 12.1 nM at sigma-2 receptor] illustrates the importance of internitrogen spacing. Triamines 11 and 13 [K-i(sigma-2)/K-i(sigma-1) = 0.19 and 0.10, respectively] containing the N-N-N-Ar spacings 3-3-2 and 4-4-2, proved to be the most sigma-2 subtype selective of the 15 polyamines examined in this study. The N-N-N spacings appear to be an important factor in their sigma-2 subtype selectivity. These compounds will serve as templates in the design of still further sigma-2 subtype selective ligands. The pyrrolidine ring (present in most of the polyamines tested in this series) proved to be an important recognition site for a receptor binding activity. Furthermore, alkyl substitution also appears to be important since the stripped down polyamines N-[2-(3,4-dichlorophenyl)ethyl]ethylenediamine (15) and N-1-[2-(3,4-dichlorophenyl)ethyl] diethylenetriamine (16) exhibited relatively low binding affinity. RP DECOSTA, BR (reprint author), NIDDKD,MED CHEM LAB,BLDG 8,ROOM B1-23,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 43 TC 21 Z9 21 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JAN 21 PY 1994 VL 37 IS 2 BP 314 EP 321 DI 10.1021/jm00028a016 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA MT292 UT WOS:A1994MT29200016 PM 8295220 ER PT J AU COVELL, DG AF COVELL, DG TI LATTICE MODEL SIMULATIONS OF POLYPEPTIDE-CHAIN FOLDING SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE PROTEIN STRUCTURE; LATTICE MODELS; TRANSITION; FOLDING ID MONTE-CARLO; PROTEIN-STRUCTURE; TERTIARY STRUCTURE; POLYMER-CHAINS; LOW-RESOLUTION; REPRESENTATION; CONFORMATIONS; INTERMEDIATE; PREDICTION; RANGE RP COVELL, DG (reprint author), NCI,FCRDC,PRI DYNCORP,FREDERICK BIOMED SUPERCOMP CTR,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 65 TC 44 Z9 45 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JAN 21 PY 1994 VL 235 IS 3 BP 1032 EP 1043 DI 10.1006/jmbi.1994.1055 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MT701 UT WOS:A1994MT70100016 PM 8289307 ER PT J AU MARQUEZ, VE LEE, JW SHARMA, R TENG, K WANG, SM LEWIN, NE BAHADOR, A KAZANIETZ, MG BLUMBERG, PM AF MARQUEZ, VE LEE, JW SHARMA, R TENG, K WANG, SM LEWIN, NE BAHADOR, A KAZANIETZ, MG BLUMBERG, PM TI CONFORMATIONALLY CONSTRAINED ANALOGS OF DIACYLGLYCEROL .6. CHANGES IN PK-C BINDING-AFFINITY FOR 3-O-ACYL-2-DEOXY-L-RIBONOLACTONES BEARING DIFFERENT ACYL CHAINS SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID PROTEIN-KINASE-C; SOLUBILITY AB Several 3-O-acyl-2-deoxy-L-ribonolactones with various acyl chains were synthesized and evaluated for their ability to compete with [H-3]phorbol-12,13-dibutyrate in a PK-C binding assay. A parabolic correlation between log 1/K-i and log water solubility [log (WS)] revealed the importance of branching of the acyl chain as a means to increase affinity. As in the case of the diacylglycerols, this effect possibly is related to the de-stabilization of the lipid bilayer induced by the presence of a ''kink'' in the modified acyl chains. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. RP MARQUEZ, VE (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892, USA. NR 16 TC 13 Z9 13 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JAN 20 PY 1994 VL 4 IS 2 BP 355 EP 360 DI 10.1016/S0960-894X(01)80144-X PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA MX613 UT WOS:A1994MX61300025 ER PT J AU KASHANCHI, F PIRAS, G RADONOVICH, MF DUVALL, JF FATTAEY, A CHIANG, CM ROEDER, RG BRADY, JN AF KASHANCHI, F PIRAS, G RADONOVICH, MF DUVALL, JF FATTAEY, A CHIANG, CM ROEDER, RG BRADY, JN TI DIRECT INTERACTION OF HUMAN TFIID WITH THE HIV-1 TRANSACTIVATOR TAT SO NATURE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; III TRANSCRIPTION FACTOR; RNA POLYMERASE-II; BINDING PROTEIN; ELONGATION; COMPONENTS; ACTIVATION; COMPLEXES; PROMOTER; INVITRO AB THE tat gene of the human immunodeficiency virus (HIV) plays a central role in the activation and life cycle of HIV. The tat protein (Tat) specifically transactivates HIV transcription in vivo and in vitro1-8, exerting its effects at the level of transcriptional initiation and elongation. Here we report that Tat binds directly to the basal transcription factor TFIID. The transcriptional activity of HeLa extracts was depleted after chromatography on a rat affinity column, which specifically retained the polymerase II-specific factor TFIID: Direct interaction of Tat with holo-TFIID, composed of TATA-binding protein (TBP) and associated factors (TAFs), was observed. Tat binds, through amino acids 36-50, directly to the TBP subunit of TFIID. Our results suggest that Tat may transduce upstream or downstream regulatory signals by direct interaction with the basal transcription factor TFIID. C1 MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. ROCKEFELLER UNIV,NEW YORK,NY 10021. RP KASHANCHI, F (reprint author), NCI,MOLEC VIROL LAB,BETHESDA,MD 20892, USA. NR 30 TC 241 Z9 243 U1 0 U2 1 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JAN 20 PY 1994 VL 367 IS 6460 BP 295 EP 299 DI 10.1038/367295a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MR494 UT WOS:A1994MR49400063 PM 8121496 ER PT J AU GEJMAN, PV RAM, A GELERNTER, J FRIEDMAN, E CAO, QH PICKAR, D BLUM, K NOBLE, EP KRANZLER, HR OMALLEY, S HAMER, DH WHITSITT, F RAO, P DELISI, LE VIRKKUNEN, M LINNOILA, M GOLDMAN, D GERSHON, ES AF GEJMAN, PV RAM, A GELERNTER, J FRIEDMAN, E CAO, QH PICKAR, D BLUM, K NOBLE, EP KRANZLER, HR OMALLEY, S HAMER, DH WHITSITT, F RAO, P DELISI, LE VIRKKUNEN, M LINNOILA, M GOLDMAN, D GERSHON, ES TI NO STRUCTURAL MUTATION IN THE DOPAMINE-D2 RECEPTOR GENE IN ALCOHOLISM OR SCHIZOPHRENIA - ANALYSIS USING DENATURING GRADIENT GEL-ELECTROPHORESIS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID POLYMERASE CHAIN-REACTION; ALPHA-SUBUNIT GENE; SCREENING-TEST; D2-DOPAMINE RECEPTOR; ALLELIC ASSOCIATION; DNA FRAGMENTS; GC-CLAMP; D2; FAMILY; DRUG AB Objective.-To examine the dopamine D2 receptor (DRD2) gene coding sequences for abnormalities associated with schizophrenia or alcoholism and thereby help to resolve the controversy surrounding the reported association of alcoholism with a restriction fragment length polymorphism located close to the DRD2 gene. Design.-Mutational analysis of complete DRD2 gene coding sequences by denaturing gradient gel electrophoresis followed by direct nucleotide sequencing of detected variants. Setting.-Patients and controls from clinical and epidemiologic collections in the United States and Europe. Patients.-A total of 253 unrelated individuals, including 106 patients with schizophrenia, 113 with alcoholism, and 34 controls. For alcoholism we included patients from previously published series in which an association of illness with allele A1 was reported (Taq I site 3' to the DRD2 gene) and from other published series in which nonconfirmations of this association were reported. Nearly all persons examined were white. Main Outcome Measures.-Frequency of nonsilent variations in DRD2 gene DNA sequences in the different diagnostic groups. Results.-We found three infrequent DNA variants that predict altered amino acid sequence of the receptor. None of these is associated with either alcoholism or schizophrenia. Conclusion.-No structural coding abnormalities in the DRD2 gene are present in alcoholism or schizophrenia. C1 NIMH, EXPTL THERAPEUT BRANCH, BETHESDA, MD 20892 USA. YALE UNIV, MED CTR, DEPT PSYCHIAT, NEW HAVEN, CT 06520 USA. VET AFFAIRS MED CTR, W HAVEN, CT USA. KAROLINSKA HOSP, DEPT CLIN GENET, S-10401 STOCKHOLM 60, SWEDEN. UNIV TEXAS, HLTH SCI CTR, DEPT PHARMACOL, SAN ANTONIO, TX 78284 USA. UNIV CALIF LOS ANGELES, NEUROPSYCHIAT INST & BRAIN RES, ALCOHOL RES CTR, LOS ANGELES, CA USA. UNIV CONNECTICUT, CTR HLTH, ALCOHOL RES CTR, FARMINGTON, CT 06032 USA. NCI, BIOCHEM LAB, BETHESDA, MD 20892 USA. SUNY STONY BROOK, HLTH SCI CTR, DEPT PSYCHIAT & BEHAV SCI, STONY BROOK, NY 11794 USA. UNIV HELSINKI, DEPT PSYCHIAT, SF-00100 HELSINKI 10, FINLAND. NIAAA, DIV INTRAMURAL CLIN & BIOL RES, CLIN STUDIES LAB, BETHESDA, MD USA. NIAAA, NEUROGENET LAB, BETHESDA, MD 20892 USA. RP GEJMAN, PV (reprint author), NIMH, CLIN & NEUROGENET BRANCH, 10-3N218, BETHESDA, MD 20892 USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU NIMH NIH HHS [MH00931] NR 69 TC 198 Z9 198 U1 2 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 19 PY 1994 VL 271 IS 3 BP 204 EP 208 DI 10.1001/jama.271.3.204 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA MQ645 UT WOS:A1994MQ64500033 PM 8277546 ER PT J AU DAY, GL BLOT, WJ SHORE, RE MCLAUGHLIN, JK AUSTIN, DF GREENBERG, RS LIFF, JM PRESTONMARTIN, S SARKAR, S SCHOENBERG, JB FRAUMENI, JF AF DAY, GL BLOT, WJ SHORE, RE MCLAUGHLIN, JK AUSTIN, DF GREENBERG, RS LIFF, JM PRESTONMARTIN, S SARKAR, S SCHOENBERG, JB FRAUMENI, JF TI 2ND CANCERS FOLLOWING ORAL AND PHARYNGEAL CANCERS - ROLE OF TOBACCO AND ALCOHOL SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID MULTIPLE PRIMARY CANCERS; PRIMARY TUMORS; RISK-FACTORS; HEAD; NECK; CARCINOMA; SMOKING; LARYNX AB Background: The exceptionally high rate of second primary cancers among patients with oral and pharyngeal cancers is well recognized, yet there has been limited epidemiologic study of risk factors for second tumors. Purpose: To evaluate the relation of smoking and alcohol consumption to the development of second cancers among this high-risk patient group, we conducted a nested case-control study. Methods: A total of 1090 patients enrolled in a 1984-1985 population-based, case-control study of oral cancer in four areas of the United States were followed through June 1989 for the occurrence of second primary cancers. Information on tobacco and alcohol consumption was obtained from the original interviews and was updated by follow-up interviews obtained for 80 case patients with second cancers and 189 sex-, study area-, and survival-matched cancer patients free of second cancers (control subjects). Results: Tobacco smoking and alcohol drinking each contributed to risk of second cancers, with the effects of smoking more pronounced than those of alcohol. The odds ratios (ORs) for smoking (adjusted for alcohol) rose with duration and intensity of smoking and were strongest for tumors of the aerodigestive tract (oral cavity, pharynx, esophagus, larynx, and lungs), with ORs reaching 4.7 (95% confidence interval [CI] = 1.4-16) among smokers of 40 or more cigarettes per day for 20 or more years. Current smokers as of the baseline survey experienced a fourfold increased risk of a second aerodigestive tract cancer relative to nonsmokers and former smokers. No reduction in risk was associated with cessation of smoking or drinking at or after the index diagnosis, although the short median interval (27 months) between tumor diagnoses limited observation of the effects due to recent cessation. Risk was significantly reduced, however, 5 years after smoking cessation. Among drinkers, second cancer risk was greatest for beer intake, with an OR for a second aerodigestive tract cancer of 3.8 (95% CI = 1.2-12) for 15 or more beers per week. Conclusions: Oral and pharyngeal cancer patients with the highest intakes of tobacco and alcohol are the ones most prone to develop second primary cancers. Implications: Avoidance of tobacco smoking and alcohol drinking is the most desirable way not only to prevent primary oral cancers, but also to reduce risk of second cancers of the aerodigestive system. C1 NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. NYU MED CTR,NEW YORK,NY 10016. CALIF DEPT HLTH SERV,EMERYVILLE,CA. EMORY UNIV,SCH PUBL HLTH,ATLANTA,GA 30322. UNIV SO CALIF,LOS ANGELES,CA 90089. NEW JERSEY DEPT HLTH,TRENTON,NJ. NR 24 TC 185 Z9 187 U1 0 U2 5 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 19 PY 1994 VL 86 IS 2 BP 131 EP 137 DI 10.1093/jnci/86.2.131 PG 7 WC Oncology SC Oncology GA MQ864 UT WOS:A1994MQ86400016 PM 8271296 ER PT J AU DECENSI, A BRUNO, S COSTANTINI, M TORRISI, R CUROTTO, A GATTESCHI, B NICOLO, G POLIZZI, A PERLOFF, M MALONE, WF BRUZZI, P AF DECENSI, A BRUNO, S COSTANTINI, M TORRISI, R CUROTTO, A GATTESCHI, B NICOLO, G POLIZZI, A PERLOFF, M MALONE, WF BRUZZI, P TI PHASE-IIA STUDY OF FENRETINIDE IN SUPERFICIAL BLADDER-CANCER, USING DNA FLOW-CYTOMETRY AS AN INTERMEDIATE END-POINT SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Note ID CARCINOGENESIS; RETINOIDS; AGENTS C1 NATL INST CANC RES,DEPT BIOPHYS,I-16132 GENOA,ITALY. NATL INST CANC RES,DEPT CLIN EPIDEMIOL,I-16132 GENOA,ITALY. UNIV GENOA,INST UROL,I-16126 GENOA,ITALY. UNIV GENOA,INST OPHTHALMOL,I-16126 GENOA,ITALY. NCI,DIV CANC PREVENT & CONTROL,CHEMOPREVENT BRANCH,BETHESDA,MD 20892. RP DECENSI, A (reprint author), NATL INST CANC RES,DEPT MED ONCOL 2,VIALE BENEDETTO XV 10,I-16132 GENOA,ITALY. RI costantini, massimo/G-1443-2012; Bruno, Silvia/B-8980-2013; OI costantini, massimo/0000-0002-5293-7079; Bruzzi, Paolo/0000-0002-7874-2077 NR 13 TC 51 Z9 51 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 19 PY 1994 VL 86 IS 2 BP 138 EP 140 DI 10.1093/jnci/86.2.138 PG 3 WC Oncology SC Oncology GA MQ864 UT WOS:A1994MQ86400017 PM 8271297 ER PT J AU BERG, SL COWAN, KH BALIS, FM FISHERMAN, JS DENICOFF, AM HILLIG, M POPLACK, DG OSHAUGHNESSY, JA AF BERG, SL COWAN, KH BALIS, FM FISHERMAN, JS DENICOFF, AM HILLIG, M POPLACK, DG OSHAUGHNESSY, JA TI PHARMACOKINETICS OF TAXOL AND DOXORUBICIN ADMINISTERED ALONE AND IN COMBINATION BY CONTINUOUS 72-HOUR INFUSION SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Note ID PHASE-I TRIAL; ADRIAMYCIN; CANCER; PLASMA C1 NCI,MED BRANCH,BETHESDA,MD 20892. RP BERG, SL (reprint author), NCI,PEDIAT BRANCH,BLDG 10,RM 13N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 20 TC 68 Z9 68 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 JAN 19 PY 1994 VL 86 IS 2 BP 143 EP 145 DI 10.1093/jnci/86.2.143 PG 3 WC Oncology SC Oncology GA MQ864 UT WOS:A1994MQ86400020 PM 7903702 ER PT J AU CHOI, IS DIAMOND, AM CRAIN, PF KOLKER, JD MCCLOSKEY, JA HATFIELD, DL AF CHOI, IS DIAMOND, AM CRAIN, PF KOLKER, JD MCCLOSKEY, JA HATFIELD, DL TI RECONSTITUTION OF THE BIOSYNTHETIC-PATHWAY OF SELENOCYSTEINE TRANSFER-RNAS IN XENOPUS-OOCYTES SO BIOCHEMISTRY LA English DT Article ID PHOSPHOSERINE TRANSFER-RNA; SPLICED TRANSFER-RNA; ANTICODON LOOP; GENE; ELEMENTS AB Selenocysteine is cotranslationally introduced into a growing polypeptide in response to certain UGA codons in selenoprotein mRNAs. The biosynthesis of this amino acid initiates by aminoacylation of specific tRNAs (designated tRNA[Se,]Sec) With serine and subsequent conversion of the serine moiety to selenocysteine. The resulting selenocysteyl-tRNA then donates selenocysteine to protein. In most higher vertebrate cells and tissues examined, multiple selenocysteine isoacceptors have been described. Two of these have been determined to differ by only a single modified residue in the wobble position of the anticodon. In addition, the steady-state levels and relative distributions of these isoacceptors have been shown to be influenced by the presence of selenium. In order to gain a better understanding of the relationship between these tRNAs and how they are regulated, both the Xenopus selenocysteine tRNA gene and an in vitro synthesized RNA have each been injected into Xenopus oocytes and their maturation analyzed. In this system, selenium enhanced RNA stability and altered the distribution of isoacceptors that differ by a single ribose methylation. Interestingly, the biosynthesis of one of these modified nucleosides (5-methylcar-boxymethyl-2'-O-methyluridine), which has been identified only in the wobble position of selenocysteine tRNA, also occurs in oocytes. Examination of the modified residues in both the naturally occurring Xenopus selenocyteine tRNA and the products generated from exogenous templates in oocytes demonstrated the faithful reconstruction of the biosynthetic pathway for these tRNAs. C1 NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637. UNIV UTAH,DEPT MED CHEM,SALT LAKE CITY,UT 84112. FU NCI NIH HHS [R01 CA54364]; NIGMS NIH HHS [R01 GM29812] NR 24 TC 32 Z9 32 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 18 PY 1994 VL 33 IS 2 BP 601 EP 605 DI 10.1021/bi00168a027 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR493 UT WOS:A1994MR49300027 PM 8286391 ER PT J AU BRADLEY, DJ TOWLE, HC YOUNG, WS AF BRADLEY, DJ TOWLE, HC YOUNG, WS TI ALPHA-THYROID AND BETA-THYROID HORMONE-RECEPTOR (TR) GENE-EXPRESSION DURING AUDITORY NEUROGENESIS - EVIDENCE FOR TR ISOFORM-SPECIFIC TRANSCRIPTIONAL REGULATION IN-VIVO SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE C-ERBA-ALPHA; C-ERBA-BETA; IN SITU HYBRIDIZATION; DEAFNESS; INNER EAR ID LIGAND-BINDING DOMAIN; GENERALIZED RESISTANCE; DIFFERENTIAL EXPRESSION; BRAIN-DEVELOPMENT; MESSENGER-RNAS; NERVOUS-SYSTEM; RAT-BRAIN; MUTATION; PROTEIN; IDENTIFICATION AB Clinicians have long recognized that congenital deficiency of iodine (a component of thyroid hormone) somehow damages the human embryonic nervous system, causing sensori-neural deafness. Recently, a deletion encompassing most of the human beta thyroid hormone receptor (TR beta) gene has been found in children who are neurologically normal except for one striking defect: profound sensori-neural deafness. We now show that the TR beta gene is prominently expressed very early in rat inner ear development. This expression is remarkable because both TR beta 1 and TR beta 2 mRNAs are restricted, as early as embryonic day 12.5, to that portion of the embryonic inner ear that gives rise to the cochlea, the structure responsible for converting sound into neural impulses. The timing of this expression, when correlated with human inner ear development, raises the possibility that TRs may act in human ontogenesis earlier than previously suspected. These results provide a rare correlation between a specific human neurologic deficit (deafness) and transcription factor expression in a highly discrete embryonic cell population (ventral otocyst). TR alpha gene expression is also prominent in the developing cochlea, but, in contrast to the restricted pattern of TR beta gene expression, TR alpha 1 and TR alpha 2 transcripts are also found in inner ear structures responsible for balance. Deafness in children homozygous for a large deletion in the TR beta gene suggests that cochlear alpha 1 TRs cannot functionally compensate for the absence of TR beta 1 and TR beta 2. The developing inner ear may, therefore, represent an example of TR isoform specific transcriptional regulation in vivo. C1 UNIV MINNESOTA,DEPT BIOCHEM,MINNEAPOLIS,MN 55455. UNIV MICHIGAN,SCH MED,ANN ARBOR,MI 48109. RP BRADLEY, DJ (reprint author), NIMH,CELL BIOL LAB,BLDG 36,ROOM 2D10,BETHESDA,MD 20892, USA. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 NR 57 TC 152 Z9 153 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 18 PY 1994 VL 91 IS 2 BP 439 EP 443 DI 10.1073/pnas.91.2.439 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MR989 UT WOS:A1994MR98900004 PM 8290545 ER PT J AU BASILION, JP ROUAULT, TA MASSINOPLE, CM KLAUSNER, RD BURGESS, WH AF BASILION, JP ROUAULT, TA MASSINOPLE, CM KLAUSNER, RD BURGESS, WH TI THE IRON-RESPONSIVE ELEMENT-BINDING PROTEIN - LOCALIZATION OF THE RNA-BINDING SITE TO THE ACONITASE ACTIVE-SITE CLEFT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE UV CROSS-LINKING; BASE HYDROLYSIS ID FERRITIN MESSENGER-RNA; SULFUR CLUSTER; IRE-BP; IDENTIFICATION; CDNA AB The iron-responsive element-binding protein (IRE-BP) binds to specific stem-loop RNA structures known as iron-responsive elements (IREs) present in a variety of cellular mRNAs (e.g., those encoding ferritin, erythroid 5-aminolevulinate synthase, and transferrin receptor). Expression of these genes is regulated by interaction with the IRE-BP. The IRE-BP is identical in sequence to cytosolic aconitase, and the Function of the protein is determined by the presence or absence of an Fe-S cluster. The protein either functions as an active aconitase when the Fe-S cluster is present of as an RNA binding protein when the protein lacks this cluster. Aconitase activity and IRE-binding activity are mutually exclusive, and interconversion between the two activities is determined by intracellular Fe concentrations. Mapping of the RNA-binding site of the IRE-BP by UV cross-linking studies defines a major contact site between IRE and protein in the active-site region. Modeling based on probable structural similarities between the previously crystallized mitochondrial aconitase and the IRE-BP predicts that these residues would be accessible to the IRE only were there a major change in the predicted conformation of the protein when cells are iron-depleted. C1 AMER RED CROSS,HOLLAND LAB,DEPT MOLEC BIOL,ROCKVILLE,MD 20855. RP BASILION, JP (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. FU NHLBI NIH HHS [HL44336, HL35762] NR 33 TC 103 Z9 102 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 18 PY 1994 VL 91 IS 2 BP 574 EP 578 DI 10.1073/pnas.91.2.574 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MR989 UT WOS:A1994MR98900031 PM 8290565 ER PT J AU DONG, ZG BIRRER, MJ WATTS, RG MATRISIAN, LM COLBURN, NH AF DONG, ZG BIRRER, MJ WATTS, RG MATRISIAN, LM COLBURN, NH TI BLOCKING OF TUMOR PROMOTER-INDUCED AP-1 ACTIVITY INHIBITS INDUCED TRANSFORMATION IN JB6 MOUSE EPIDERMAL-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE C-JUN; PHORBOL ESTERS; EPIDERMAL GROWTH FACTOR; CELL TRANSFORMATION ID C-JUN; RETINOIC ACID; DNA-BINDING; NEOPLASTIC TRANSFORMATION; GLUCOCORTICOID RECEPTOR; PROTO-ONCOPROTEIN; GENE; FOS; EXPRESSION; STROMELYSIN AB AP-1 transcriptional activity is stimulated by the transformation promoters phorbol 12-myristate 13-acetate (''12-0-tetradecanoyIphorbol 13 acetate,'' TPA) and epidermal growth factor (EGF) in promotion-sensitive (pf) but not in promotion-resistant (P-) JB6 mouse epidermal cell lines. Although TPA stimulates expression of the jun and fos family genes, only c-jun expression shows higher elevation in P+ cells than in P- cells. The present study tests the hypothesis that induced AP-1 activity is required for tumor promoter induced transformation in JB6 P+ cells. Both retinoic acid and the glucocorticoid fluocinolone acetonide inhibited basal and TPA-induced AP-1 activities that were tested with a stromelysin promoter-chloramphenicol acetyltransferase reporter gene in P+ cells. Since both retinoic acid and fluocinolone acetonide are active in inhibiting TPA-induced anchorage-independent transformation of P+ cells in the dose range that blocks TPA-induced AP-1 activity, their antipromoting effects may occur through inhibition of AP-1 activity. To test the hypothesis with a more specific inhibitor, stable clonal transfectants of P+ cells expressing dominant negative c-jun mutant encoding a transcriptionally inactive product were analyzed. All transfectants showed a block in TPA and EGF induction of AP-1 activity. Ah transfectants also showed inhibition of TPA-induced transformation, and most transfectants showed a block in EGF-induced transformation. These results indicate that AP-1 activity is required for TPA- or EGF-induced transformation. This work demonstrates that a specific block in induced AP-I activity inhibits tumor promoter-induced transformation. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,CELL BIOL SECT,FREDERICK,MD 21702. NCI,BIOMARKERS & PREVENT RES BRANCH,BETHESDA,MD 20814. VANDERBILT UNIV,SCH MED,DEPT CELL BIOL,NASHVILLE,TN 37232. RP DONG, ZG (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK,MD 21702, USA. NR 34 TC 328 Z9 334 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 18 PY 1994 VL 91 IS 2 BP 609 EP 613 DI 10.1073/pnas.91.2.609 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MR989 UT WOS:A1994MR98900038 PM 8290571 ER PT J AU WU, JC MERLINO, G FAUSTO, N AF WU, JC MERLINO, G FAUSTO, N TI ESTABLISHMENT AND CHARACTERIZATION OF DIFFERENTIATED, NONTRANSFORMED HEPATOCYTE CELL-LINES DERIVED FROM MICE TRANSGENIC FOR TRANSFORMING GROWTH-FACTOR-ALPHA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE LIVER; HEPATOCARCINOGENESIS; GROWTH FACTORS; LIVER REGENERATION; CELL CULTURE ID RAT HEPATOCYTES; OVAL CELLS; EPITHELIAL-CELLS; C-MYC; LIVER; EXPRESSION; GENES; RNAS; OVEREXPRESSION; TRANSFECTION AB Hepatocytes are extensively used in studies of gene regulation but cannot be maintained in long-term culture as replicating, differentiated cells while remaining nontumorigenic. We have derived two hepatocyte lines from livers of transgenic mice overexpressing transforming growth factor a, a potent hepatocyte mitogen, which overcome these limitations. The transgenic hepatocytes were maintained for greater than or equal to 2 months in serum-supplemented primary culture and gave rise to cell lines, of which two (AML12 and AML14) have been cultured for >1.5 years (>80 passages). Both lines have typical hepatocyte features such as peroxisomes and bile canalicular-like structures, do not grow in soft agar, and are nontumorigenic in nude mice. Like normal hepatocytes, AML cells express high levels of mRNA for serum (albumin, alpha(1)-antitrypsin, and transferrin) and gap junction (connexins 26 and 32) proteins, secrete albumin, and contain solely isozyme 5 of lactate dehydrogenase. After extensive passaging, AML12 cells continue to strongly coexpress hepatocyte connexin mRNAs but do not display nonparenchymal cell markers, Although mRNA levels for some serum proteins progressively fall, high expression in late AML12 cultures may be regained by passage in serum-free medium. The AML14 line loses expression of both differentiated markers and transgene mRNA with extended passaging, and hepatocytic traits are only partially restored by passage in serum-free medium. These differentiated, nontumorigenic cell lines should serve as models in which to study hepatocyte growth and differentiation. C1 BROWN UNIV,DEPT PATHOL & LAB MED,PROVIDENCE,RI 02912. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA23226] NR 38 TC 198 Z9 198 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 18 PY 1994 VL 91 IS 2 BP 674 EP 678 DI 10.1073/pnas.91.2.674 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MR989 UT WOS:A1994MR98900051 PM 7904757 ER PT J AU ZEIGER, E AF ZEIGER, E TI STRATEGIES AND PHILOSOPHIES OF GENOTOXICITY TESTING - WHAT IS THE QUESTION SO MUTATION RESEARCH LA English DT Article DE SALMONELLA; CYTOGENETICS; IN VITRO; MICRONUCLEUS TEST; MAMMALIAN CELLS; MAMMALIAN CELL GENE MUTATION; CARCINOGENICITY PREDICTION ID GENETIC TOXICITY TESTS; TERM TEST INFORMATION; CARCINOGENICITY; MUTAGENICITY; CHEMICALS; ASSAYS; SALMONELLA; PROGRAM AB A number of statements concerning the uses and effectiveness of in vitro and in vivo genetic toxicity tests have recently been made. Certain of these statements are examined using genetic toxicity and carcinogenicity data available in the literature. RP ZEIGER, E (reprint author), NIEHS,ENVIRONM TOXICOL PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 23 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD JAN 16 PY 1994 VL 304 IS 2 BP 309 EP 314 DI 10.1016/0027-5107(94)90225-9 PG 6 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA MT851 UT WOS:A1994MT85100019 PM 7506375 ER PT J AU BURKHART, JG MALLING, HV AF BURKHART, JG MALLING, HV TI MUTATIONS AMONG THE LIVING AND THE UNDEAD SO MUTATION RESEARCH LA English DT Article DE TRANSGENES; MUTANT FREQUENCIES; CELL DYNAMICS ID DELAYED REPRODUCTIVE DEATH; MOUSE-GERM-CELLS; SPERM ABNORMALITIES; LOCUS TEST; MICE; FREQUENCY; ETHYLNITROSOUREA; PHENOTYPE; ASSAYS; CARCINOGENESIS RP BURKHART, JG (reprint author), NIEHS,GENET LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 35 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD JAN 16 PY 1994 VL 304 IS 2 BP 315 EP 320 DI 10.1016/0027-5107(94)90226-7 PG 6 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA MT851 UT WOS:A1994MT85100020 PM 7506376 ER PT J AU SHIRANI, J ROBERTS, WC AF SHIRANI, J ROBERTS, WC TI STATUS OF THE MAJOR EPICARDIAL CORONARY-ARTERIES AT NECROPSY IN PARAPLEGIA AND QUADRIPLEGIA SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Note C1 NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. NR 0 TC 4 Z9 4 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 15 PY 1994 VL 73 IS 2 BP 207 EP 208 DI 10.1016/0002-9149(94)90217-8 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA MR545 UT WOS:A1994MR54500020 PM 8296746 ER PT J AU SIMON, JA OBARZANEK, E DANIELS, SR FREDERICK, MM AF SIMON, JA OBARZANEK, E DANIELS, SR FREDERICK, MM TI DIETARY CATION INTAKE AND BLOOD-PRESSURE IN BLACK GIRLS AND WHITE GIRLS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE BLOOD PRESSURE; CALCIUM; CATIONS; DIETARY FIBER; MAGNESIUM; POTASSIUM; SODIUM; WOMEN ID PLASMA-RENIN ACTIVITY; MAGNESIUM SUPPLEMENTATION; URINARY CATIONS; ORAL MAGNESIUM; POTASSIUM; SODIUM; CHILDREN; HYPERTENSION; CALCIUM; ELECTROLYTES AB The authors examined the relative importance of dietary sodium, potassium, calcium, and magnesium intakes as correlates of blood pressure in a cross-sectional analysis of 987 black and 1,043 white 9- and 10-year-old girls from Richmond, California, Cincinnati, Ohio, and Washington, DC, who were enrolled in the National Heart, Lung, and Brood Institute Growth and Health Study between January 1987 and May 1988. Dietary intake was measured using a 3-day food record. Dietary cation intake was not associated with blood pressure in black girls. An inverse association between magnesium intake and diastolic (fifth Korotkoff phase) blood pressure was found in white girls (p < 0.01). After controlling for factors often associated with blood pressure, such as pulse rate, body mass index, and household income, the authors found that dietary magnesium intake (range, 53-511 mg/day) continued to be associated with diastolic (fifth Korotkoff phase) blood pressure in white girls, such that each 100-mg/day increase in intake was associated with a 3.22-mmHg decrease in diastolic pressure (95% confidence interval -5.70 to -0.75). However, after adjustment for dietary fiber intake, the authors were no longer able to discern an association between dietary magnesium intake and blood pressure. They conclude that the body mass index and pulse rate are the strongest correlates of blood pressure in 9- and 10-year-old black girls and white girls and that studies examining the relation between dietary magnesium and blood pressure should control for the effects of dietary fiber intake. C1 UNIV CALIF SAN FRANCISCO,DEPT EPIDEMIOL & BIOSTAT,DIV CLIN EPIDEMIOL,SAN FRANCISCO,CA 94143. NHLBI,BETHESDA,MD. UNIV CINCINNATI,CHILDRENS HOSP MED CTR,DEPT PEDIAT,DIV CARDIOL,CINCINNATI,OH. MARYLAND MED RES INST,BALTIMORE,MD. RP SIMON, JA (reprint author), VET AFFAIRS MED CTR,DEPT MED,GEN INTERNAL MED SECT 111A1,4150 CLEMENT ST,SAN FRANCISCO,CA 94121, USA. FU NHLBI NIH HHS [N0 1-HC-55023-26] NR 51 TC 21 Z9 22 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 15 PY 1994 VL 139 IS 2 BP 130 EP 140 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA MV274 UT WOS:A1994MV27400002 PM 8296780 ER PT J AU KUMANYIKA, SK LANDIS, JR MATTHEWS, YL WEAVER, SL HARLAN, LC HARLAN, WR AF KUMANYIKA, SK LANDIS, JR MATTHEWS, YL WEAVER, SL HARLAN, LC HARLAN, WR TI SECULAR TRENDS IN BLOOD-PRESSURE AMONG ADULT BLACKS AND WHITES AGED 18-34 YEARS IN 2-BODY-MASS INDEX STRATA, UNITED-STATES, 1960-1980 SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE BLACKS; BLOOD PRESSURE; BODY MASS INDEX; BODY WEIGHT; HYPERTENSION; OBESITY ID HYPERTENSION AB Secular trends in blood pressure among young adults reflect the proportion of the population at risk of developing hypertension and may be markers of progress in primary prevention. National health examination data from three successive surveys were analyzed to assess blood pressure trends for adult blacks and whites aged 18-34 years in two body mass index (BMI; weight (kg)/height (m)(2)) strata (< 25 or greater than or equal to 25). Blood pressure was categorized into a four-point ordinal scale using the weighted, within-sex 50th, 75th, and 90th percentiles for 18- to 24-year-old adults in the 1960-1962 survey. The effects were analyzed with cumulative legit models with alpha = 0.01. The systolic blood pressure decreased moderately for 25- to 34-year-old males and for females except those aged 25-34 years with a BMI of greater than or equal to 25. Diastolic blood pressure increased among males with a BMI of greater than or equal to 25 and among white males with a BMI of < 25, but did not show a significant overall trend among females. A BMI of greater than or equal to 25 was associated with substantially higher blood pressure in each survey, except for one age-sex-race subgroup. Racial differences within BMI were less consistent than the differences across BMI strata. in summary, the situation with respect to hypertension among females may have improved during this time period but for males may have worsened with respect to diastolic blood pressure. Data for both sexes support a need for population-wide obesity prevention to reduce the incidence of hypertension. C1 NIH,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. RP KUMANYIKA, SK (reprint author), PENN STATE UNIV,COLL MED,CTR BIOSTAT & EPIDEMIOL,POB 850,HERSHEY,PA 17033, USA. RI Landis, J. Richard/A-9330-2010 FU NHLBI NIH HHS [PHS 5 R01 HL 33407] NR 28 TC 9 Z9 9 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 15 PY 1994 VL 139 IS 2 BP 141 EP 154 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA MV274 UT WOS:A1994MV27400003 PM 8296781 ER PT J AU KOELLER, JA FINLEY, RS GOLDSPIEL, BR LINDLEY, CM BALMER, CM BOURRET, JA DOZIER, N GREEN, L IGNOFFO, RJ SCOTT, KA SIEGEL, J AF KOELLER, JA FINLEY, RS GOLDSPIEL, BR LINDLEY, CM BALMER, CM BOURRET, JA DOZIER, N GREEN, L IGNOFFO, RJ SCOTT, KA SIEGEL, J TI EXECUTIVE SUMMARY OF PETITION REQUESTING SPECIALTY RECOGNITION OF ONCOLOGY PHARMACY PRACTICE - TASK-FORCE ON SPECIALTY RECOGNITION OF ONCOLOGY PHARMACY PRACTICE SO AMERICAN JOURNAL OF HOSPITAL PHARMACY LA English DT Article C1 UNIV MARYLAND,SCH PHARM,BALTIMORE,MD. UNIV MARYLAND,CTR CANC,BALTIMORE,MD. NIH,DEPT PHARM,BETHESDA,MD. UNIV N CAROLINA,SCH PHARM,CHAPEL HILL,NC. UNIV COLORADO,HLTH SCI CTR,SCH PHARM,DENVER,CO. UNIV PENN,MED CTR,DEPT PHARM,PHILADELPHIA,PA 19104. UNIV TEXAS,MD ANDERSON CANC CTR,PHARM CLIN PROGRAMS,HOUSTON,TX. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA. GOOD SAMARITAN HOSP PHARM,PORTLAND,OR. OHIO STATE UNIV HOSP,COLUMBUS,OH. RP KOELLER, JA (reprint author), UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 0002-9289 J9 AM J HOSP PHARM JI Am. J. Hosp. Pharm. PD JAN 15 PY 1994 VL 51 IS 2 BP 219 EP 224 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MU538 UT WOS:A1994MU53800016 ER PT J AU METZ, DC FISHBEYN, VA JENSEN, RT AF METZ, DC FISHBEYN, VA JENSEN, RT TI ASSESSING THE CURE OF THE ZOLLINGER-ELLISON SYNDROME AFTER GASTRINOMA RESECTION - REPLY SO ANNALS OF INTERNAL MEDICINE LA English DT Letter RP METZ, DC (reprint author), NIDDKD,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 15 PY 1994 VL 120 IS 2 BP 165 EP 165 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA MQ671 UT WOS:A1994MQ67100013 ER PT J AU THOMAS, DL QUINN, TC AF THOMAS, DL QUINN, TC TI THE COURSE OF NON-A, NON-B-HEPATITIS UNRELATED TO TRANSFUSION SO ANNALS OF INTERNAL MEDICINE LA English DT Letter ID C VIRUS C1 NIH,BETHESDA,MD 20892. RP THOMAS, DL (reprint author), JOHNS HOPKINS MED INST,BALTIMORE,MD 21205, USA. NR 5 TC 7 Z9 6 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 15 PY 1994 VL 120 IS 2 BP 171 EP 171 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA MQ671 UT WOS:A1994MQ67100031 PM 8256987 ER PT J AU GRZEGORZEWSKI, K KOMSCHLIES, KL MORI, M KANEDA, K USUI, N FALTYNEK, CR KELLER, JR RUSCETTI, FW WILTROUT, RH AF GRZEGORZEWSKI, K KOMSCHLIES, KL MORI, M KANEDA, K USUI, N FALTYNEK, CR KELLER, JR RUSCETTI, FW WILTROUT, RH TI ADMINISTRATION OF RECOMBINANT HUMAN INTERLEUKIN-7 TO MICE INDUCES THE EXPORTATION OF MYELOID PROGENITOR CELLS FROM THE BONE-MARROW TO PERIPHERAL SITES SO BLOOD LA English DT Article ID LARGE GRANULAR LYMPHOCYTES; COLONY-STIMULATING FACTOR; NATURAL-KILLER ACTIVITY; LONG-TERM CULTURE; GROWTH-FACTOR; RESPONSE MODIFIERS; BLOOD MONOCYTES; IL-7; LIVER; PRECURSORS C1 NCI,FCRDC,BLDG 560,RM 31-93,FREDERICK,MD 21702. INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,PROGRAM RESOURCES,EXPTL IMMUNOL LAB,FREDERICK,MD. INC DYNCORP,LEWROCYTE BIOL LABS,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD. STERLING WINTHROP INC,COLLEGEVILLE,PA. NR 37 TC 41 Z9 42 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JAN 15 PY 1994 VL 83 IS 2 BP 377 EP 385 PG 9 WC Hematology SC Hematology GA MR986 UT WOS:A1994MR98600011 PM 8286738 ER PT J AU KREITMAN, RJ BAILON, P CHAUDHARY, VK FITZGERALD, DJP PASTAN, I AF KREITMAN, RJ BAILON, P CHAUDHARY, VK FITZGERALD, DJP PASTAN, I TI RECOMBINANT IMMUNOTOXINS CONTAINING ANTI-TAC(FV) AND DERIVATIVES OF PSEUDOMONAS EXOTOXIN PRODUCE COMPLETE REGRESSION IN MICE OF AN INTERLEUKIN-2 RECEPTOR-EXPRESSING HUMAN CARCINOMA SO BLOOD LA English DT Article ID T-CELL LEUKEMIA; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CHRONIC LYMPHOCYTIC-LEUKEMIA; CARDIAC ALLOGRAFT SURVIVAL; SINGLE-CHAIN IMMUNOTOXIN; DIPHTHERIA-TOXIN; FUSION PROTEIN; IL-2 RECEPTOR; MONOCLONAL-ANTIBODIES; VARIABLE DOMAINS C1 NCI,DIV CANC BIOL & DIAG,MOLEC BIOL LAB,9000 ROCKVILLE PIKE,BLDG 37,RM 4E16,BETHESDA,MD 20892. HOFFMANN LA ROCHE INC,DEPT PROT BIOCHEM,NUTLEY,NJ 07110. UNIV DELHI,DEPT BIOCHEM,DELHI 110007,INDIA. NR 51 TC 127 Z9 130 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JAN 15 PY 1994 VL 83 IS 2 BP 426 EP 434 PG 9 WC Hematology SC Hematology GA MR986 UT WOS:A1994MR98600017 PM 8286741 ER PT J AU KAUFMANN, SH KARP, JE JONES, RJ MILLER, CB SCHNEIDER, E ZWELLING, LA COWAN, K WENDEL, K BURKE, PJ AF KAUFMANN, SH KARP, JE JONES, RJ MILLER, CB SCHNEIDER, E ZWELLING, LA COWAN, K WENDEL, K BURKE, PJ TI TOPOISOMERASE-II LEVELS AND DRUG-SENSITIVITY IN ADULT ACUTE MYELOGENOUS LEUKEMIA SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; CHINESE-HAMSTER OVARY; P-GLYCOPROTEIN EXPRESSION; ACUTE MYELOCYTIC-LEUKEMIA; BONE-MARROW TRANSPLANTATION; ACUTE MYELOBLASTIC-LEUKEMIA; INDUCED DNA CLEAVAGE; CELL-CYCLE; MULTIDRUG RESISTANCE; CYTO-TOXICITY C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PHARMACOL & MOLEC SCI,BALTIMORE,MD 21205. NCI,MED BRANCH,BETHESDA,MD 20892. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT CLIN INVEST,HOUSTON,TX 77030. RP KAUFMANN, SH (reprint author), JOHNS HOPKINS UNIV HOSP,CTR ONCOL 1-127,600 N WOLFE ST,BALTIMORE,MD 21287, USA. FU NCI NIH HHS [CA 50435] NR 94 TC 119 Z9 120 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 JAN 15 PY 1994 VL 83 IS 2 BP 517 EP 530 PG 14 WC Hematology SC Hematology GA MR986 UT WOS:A1994MR98600029 PM 7904487 ER PT J AU DEBOER, M HILARIUSSTOKMAN, PM HOSSLE, JP VERHOEVEN, AJ GRAF, N KENNEY, RT SEGER, R ROOS, D AF DEBOER, M HILARIUSSTOKMAN, PM HOSSLE, JP VERHOEVEN, AJ GRAF, N KENNEY, RT SEGER, R ROOS, D TI AUTOSOMAL RECESSIVE CHRONIC GRANULOMATOUS-DISEASE WITH ABSENCE OF THE 67-KD CYTOSOLIC NADPH OXIDASE COMPONENT - IDENTIFICATION OF MUTATION AND DETECTION OF CARRIERS SO BLOOD LA English DT Article ID RESPIRATORY BURST ACTIVATION; HUMAN-NEUTROPHILS; MICROBICIDAL OXIDASE; CYTOCHROME-B; DEFICIENCIES; SYSTEM; CHAIN C1 NETHERLANDS RED CROSS,BLOOD TRANSFUS SERV,CENT LAB,AMSTERDAM,NETHERLANDS. UNIV AMSTERDAM,EXPTL & CLIN IMMUNOL LAB,AMSTERDAM,NETHERLANDS. UNIV ZURICH,CHILDRENS HOSP,DIV IMMUNOL HAEMATOL,CH-8006 ZURICH,SWITZERLAND. UNIV HOMBURG,CHILDRENS HOSP,DEPT HEMATOL ONCOL,W-6650 HOMBURG,GERMANY. NIAID,HOST DEF LAB,BETHESDA,MD 20892. RI Graf, Norbert/H-1328-2011 OI Graf, Norbert/0000-0002-2248-323X NR 29 TC 40 Z9 41 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 JAN 15 PY 1994 VL 83 IS 2 BP 531 EP 536 PG 6 WC Hematology SC Hematology GA MR986 UT WOS:A1994MR98600030 PM 8286749 ER PT J AU BOSCO, MC GUSELLA, GL ESPINOZADELGADO, I LONGO, DL VARESIO, L AF BOSCO, MC GUSELLA, GL ESPINOZADELGADO, I LONGO, DL VARESIO, L TI INTERFERON-GAMMA UP-REGULATES INTERLEUKIN-8 GENE-EXPRESSION IN HUMAN MONOCYTIC CELLS BY A POSTTRANSCRIPTIONAL MECHANISM SO BLOOD LA English DT Article ID NEUTROPHIL CHEMOTACTIC FACTOR; TUMOR-NECROSIS-FACTOR; ATTRACTANT ACTIVATION PROTEIN-1; MESSENGER-RNA EXPRESSION; IFN-GAMMA; FACTOR-ALPHA; PERITONEAL-MACROPHAGES; HUMAN-FIBROBLASTS; EPITHELIAL-CELLS; IL-8 GENE C1 NCI,FREDERICK CANC RES & DEV CTR,MOLEC IMMUNOREGULAT LAB,BRMP,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,INC DYNCORP,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC CTR,BRMP,FREDERICK,MD 21701. NIH,MED BRANCH,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. RP BOSCO, MC (reprint author), NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,BRMP,BLDG 560,ROOM 31-51,FREDERICK,MD 21702, USA. RI Bosco, Maria Carla/J-7928-2016; varesio, luigi/J-8261-2016 OI Bosco, Maria Carla/0000-0003-1857-7193; varesio, luigi/0000-0001-5659-2218 NR 49 TC 55 Z9 55 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JAN 15 PY 1994 VL 83 IS 2 BP 537 EP 542 PG 6 WC Hematology SC Hematology GA MR986 UT WOS:A1994MR98600031 PM 8286750 ER PT J AU HENRIKSEN, TB WILCOX, A AF HENRIKSEN, TB WILCOX, A TI ULTRASOUND DATING SUBJECT TO BIAS SO BRITISH MEDICAL JOURNAL LA English DT Letter C1 NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. RP HENRIKSEN, TB (reprint author), AARHUS UNIV HOSP,DEPT OBSTET & GYNAECOL,PERINATAL EPIDEMIOL RES UNIT,DK-8000 AARHUS,DENMARK. NR 2 TC 1 Z9 1 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD JAN 15 PY 1994 VL 308 IS 6922 BP 201 EP 201 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA MR974 UT WOS:A1994MR97400051 ER PT J AU DONELLADEANA, A KRINKS, MH RUZZENE, M KLEE, C PINNA, LA AF DONELLADEANA, A KRINKS, MH RUZZENE, M KLEE, C PINNA, LA TI DEPHOSPHORYLATION OF PHOSPHOPEPTIDES BY CALCINEURIN (PROTEIN PHOSPHATASE 2B) SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article ID SUBSTRATE-SPECIFICITY; KINASE; PHOSPHORYLATION; SEQUENCE; PHOSPHOPROTEINS; DETERMINANTS; RECOGNITION; THREONINE; RECEPTOR; RESIDUES AB 38 (6-32 residues) enzymically phosphorylated synthetic peptides have been assayed as substrates for calcineurin, a Ca2+/calmodulin-dependent protein phosphatase (PP-2B) belonging to the family of Ser/Thr-specific enzymes but also active on phosphotyrosine residues. Many peptides reproduce, with suitable modifications, naturally occurring phosphoacceptor sites. While protein phosphatases 2A and 2C are also very active on short phosphopeptides, an extended N-terminal stretch appears to be a necessary, albeit not sufficient, condition for an optimal dephosphorylation, comparable to that of protein substrates, of both phosphoseryl and phosphotyrosyl peptides by calcineurin. This finding corroborates the view that higher-order structure is an important determinant for the substrate specificity of calcineurin. However, a number of shorter peptides are also appreciably dephosphorylated by this enzyme, their efficiency as substrates depending on local structural features. All the peptides that are appreciably dephosphorylated by calcineurin contain basic residue(s) on the N-terminal side. A basic residue located at position -3 relative to the phosphorylated residue plays a particularly relevant positive role in determining the dephosphorylation of short phosphopeptides. Acidic residue(s) adjacent to the C-terminal side of the phosphoamino acid are conversely powerful negative determinants, preventing the dephosphorylation of otherwise suitable peptide substrates. However, calcineurin displays an only moderate preference for phosphothreonyl peptides which are conversely strikingly preferred over their phosphoseryl counterparts by the other classes of Ser/Thr-specific protein phosphatases. Moreover calcineurin does not perceive as a strong negative determinant the motif Ser/Thr-Pro in peptides where this motif prevents dephosphorylation by the other classes of Ser/Thr protein phosphatases. Whenever tested on phosphotyrosyl peptides, calcineurin exhibits a specificity which is strikingly different from that of T-cell protein tyrosine phosphatase, a bona fide protein tyrosine phosphatase. In particular while the latter enzyme is especially active toward a number of phosphopeptides reproducing the phosphoacceptor sites of src products and of calmodulin whose N-terminal moieties are predominantly acidic, the artificial substrate phospho-angiotensin II, bearing an arginine residue at position -2, is far preferred by calcineurin over all phosphotyrosyl peptides of similar size. Collectively taken these results show that the specificity of calcineurin, rather than resting on a given consensus sequence, is determined by a variety of primary and higher-order structural features conferring to it an overall selectivity that is different from those of any other known protein phosphatase. C1 UNIV PADUA,CNR,CTR STUDIO FISIOL MITOCONDRIALE,PADUA,ITALY. NCI,BIOCHEM LAB,BETHESDA,MD 20892. RP DONELLADEANA, A (reprint author), UNIV PADUA,DIPARTIMENTO CHIM BIOL,VIA TRIESTE 75,I-35121 PADUA,ITALY. OI Ruzzene, Maria/0000-0001-8712-8151 NR 27 TC 62 Z9 62 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD JAN 15 PY 1994 VL 219 IS 1-2 BP 109 EP 117 DI 10.1111/j.1432-1033.1994.tb19920.x PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR858 UT WOS:A1994MR85800012 PM 7508382 ER PT J AU YAMAZAKI, T NICHOLSON, LK TORCHIA, DA STAHL, SJ KAUFMAN, JD WINGFIELD, PT DOMAILLE, PJ CAMPBELLBURK, S AF YAMAZAKI, T NICHOLSON, LK TORCHIA, DA STAHL, SJ KAUFMAN, JD WINGFIELD, PT DOMAILLE, PJ CAMPBELLBURK, S TI SECONDARY STRUCTURE AND SIGNAL ASSIGNMENTS OF HUMAN-IMMUNODEFICIENCY-VIRUS-1 PROTEASE COMPLEXED TO A NOVEL, STRUCTURE-BASED INHIBITOR SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article ID MAGNETIC-RESONANCE SPECTROSCOPY; ISOTOPICALLY ENRICHED PROTEINS; NMR-SPECTROSCOPY; LARGER PROTEINS; HETERONUCLEAR NMR; AQUEOUS-SOLUTION; C-13; N-15; H-1; HYDRATION AB We report comprehensive NMR studies in solution of the human-immunodeficiency-virus (HIV)-1 protease. Stable solutions of the protease were obtained by complexing the protein to a designed cyclic urea inhibitor DMP 323. A variety of triple-resonance experiments provided essentially complete H-1, C-13 and N-15 NMR signal assignments of the protease. These assignments, together with short-range NOE constraints, coupling constants and hydrogen-exchange data, yielded the secondary structure of the protease in solution. The results reported herein open the way to the determination of the high-resolution three-dimensional solution structures of protease/inhibitor complexes, as well as to studies of protease dynamics and solvent interactions. C1 NIH,OFF DIRECTOR,PROTEIN EXPRESS LAB,BETHESDA,MD 20892. NIDR,BONE RES BRANCH,BETHESDA,MD 20892. DUPONT MERCK PHARMACEUT CO,DEPT CHEM & PHYS SCI,WILMINGTON,DE. NR 30 TC 29 Z9 29 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD JAN 15 PY 1994 VL 219 IS 1-2 BP 707 EP 712 DI 10.1111/j.1432-1033.1994.tb19987.x PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR858 UT WOS:A1994MR85800079 PM 8307036 ER PT J AU ATTWOOD, J CHIANO, M COLLINS, A DONISKELLER, H DRACOPOLI, N FOUNTAIN, J FALK, C GOUDIE, D GUSELLA, J HAINES, J ARMOUR, JAL JEFFREYS, AJ KWIATKOWSKI, D LATHROP, M MATISE, T NORTHRUP, H PERICAKVANCE, MA PHILLIPS, J RETIEF, A ROBSON, E SHIELDS, D SLAUGENHAUPT, S VERGNAUD, G WEBER, J WEISSENBACH, J WHITE, R YATES, J POVEY, S AF ATTWOOD, J CHIANO, M COLLINS, A DONISKELLER, H DRACOPOLI, N FOUNTAIN, J FALK, C GOUDIE, D GUSELLA, J HAINES, J ARMOUR, JAL JEFFREYS, AJ KWIATKOWSKI, D LATHROP, M MATISE, T NORTHRUP, H PERICAKVANCE, MA PHILLIPS, J RETIEF, A ROBSON, E SHIELDS, D SLAUGENHAUPT, S VERGNAUD, G WEBER, J WEISSENBACH, J WHITE, R YATES, J POVEY, S TI CEPH CONSORTIUM MAP OF CHROMOSOME-9 SO GENOMICS LA English DT Article ID LINKAGE MAP; GORLIN SYNDROME; HUMAN GENOME; GENE; DELETIONS; MELANOMA AB This paper describes the Centre d'Etude du Polymorphisme Humain (CEPH) consortium linkage map of chromosome 9. A total of 124 markers were typed in the CEPH family DNAs by 14 contributing laboratories; of these, 42 loci are ordered on the map with likelihood support of at least 1000:1. The uniquely placed markers include 31 that can be typed by PCR. A further 28 markers that can be typed by PCR are approximately positioned on the map. Multilocus linkage analysis with CRI-MAP has produced male, female, and sex-averaged maps extending for 176, 237, and 209 cM, respectively, while sex-averaged maps produced with MAPMAKER and the multiple two-point program MAP extended for 170 and 129 cM, respectively. The male map contains only two intervals greater than 10 cM, and the mean genetic distance between the 42 uniquely placed loci is 4.3 cM. However, no markers were available to anchor the map at either telomere or the centromere. The results confirm the high level of interference suggested by chiasma maps of chromosome 9. Detailed meiotic breakpoints for three of the families are shown. These can be used to provide rapid placement of any new marker without the need for statistical analysis. (C) 1994 Academic Press, Inc. C1 UNIV CAMBRIDGE, DEPT PATHOL, CAMBRIDGE CB2 1QP, CAMBS, ENGLAND. PRINCESS ANNE HOSP, CRC, DEPT CHILD HLTH, GENET EPIDEMIOL RES GRP, SOUTHAMPTON SO9 4HA, HANTS, ENGLAND. WASHINGTON UNIV, SCH MED, DEPT GENET, ST LOUIS, MO 63110 USA. NIH, NATL CTR HUMAN GENOME RES, BETHESDA, MD 20892 USA. MIT, CTR CANC RES, CAMBRIDGE, MA 02139 USA. NEW YORK BLOOD CTR, POPULAT GENET LAB, NEW YORK, NY 10021 USA. MASSACHUSETTS GEN HOSP, MOLEC NEUROGENET UNIT, BOSTON, MA 02129 USA. MASSACHUSETTS GEN HOSP, NEUROGENET LAB, BOSTON, MA 02114 USA. UNIV LEICESTER, DEPT GENET, LEICESTER LE1 7RH, ENGLAND. BRIGHAM & WOMENS HOSP, DIV EXPTL MED, BOSTON, MA 02115 USA. CEPH, F-75010 PARIS, FRANCE. UNIV PITTSBURGH, PITTSBURGH, PA 15261 USA. UNIV TEXAS, SCH MED, DEPT PEDIAT, DIV GENET, HOUSTON, TX 77225 USA. DUKE UNIV, MED CTR, DIV NEUROL, DURHAM, NC 27710 USA. VANDERBILT UNIV, MED CTR, DIV GENET, NASHVILLE, TN 37232 USA. UNIV STELLENBOSCH, FAC AGR SCI, DEPT GENET, STELLENBOSCH 7600, SOUTH AFRICA. UCL, DEPT GENET & BIOMETRY, GALTON LAB, LONDON NW1 2HE, ENGLAND. CTR ETUD BOUCHET, F-91710 VERT LE PETIT, FRANCE. MARSHFIELD MED RES FDN, MARSHFIELD, WI 54449 USA. INST PASTEUR, F-75724 PARIS 15, FRANCE. UNIV UTAH, HOWARD HUGHES MED INST, SALT LAKE CITY, UT 84112 USA. RP ATTWOOD, J (reprint author), UCL, GALTON LAB,MRC,HUMAN BIOCHEM GENET UNIT, WOLFSON HOUSE, 4 STEPHENSON WAY, LONDON NW1 2HE, ENGLAND. RI Collins, Andrew/A-6595-2010; Haines, Jonathan/C-3374-2012; Vergnaud, Gilles/P-1304-2015 OI Collins, Andrew/0000-0001-7108-0771; Vergnaud, Gilles/0000-0003-0913-194X FU NHGRI NIH HHS [HG00598]; NIGMS NIH HHS [GM29177]; Wellcome Trust NR 36 TC 25 Z9 25 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JAN 15 PY 1994 VL 19 IS 2 BP 203 EP 214 DI 10.1006/geno.1994.1049 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NA603 UT WOS:A1994NA60300001 PM 8188250 ER PT J AU TOMBRANTINK, J PAWAR, H SWAROOP, A RODRIQUEZ, I CHADER, GJ AF TOMBRANTINK, J PAWAR, H SWAROOP, A RODRIQUEZ, I CHADER, GJ TI LOCALIZATION OF THE GENE FOR PIGMENT EPITHELIUM-DERIVED FACTOR (PEDF) TO CHROMOSOME 17P13.1 AND EXPRESSION IN CULTURED HUMAN RETINOBLASTOMA CELLS SO GENOMICS LA English DT Article ID P53 MUTATIONS; BREAST-CANCER; HYBRIDS; TUMORS; LOCUS AB The gene for pigment epithelium-derived factor (PEDF) was localized to chromosome 17 by the analysis of three independent somatic cell hybrid panels. Fluorescence in situ hybridization shows a specific hybridization signal at the terminal portion of the short arm of chromosome 17. PCR analysis of somatic cell hybrids containing specific regions of 17 was subsequently used to sublocalize PEDF to 17p13.1-pter. PEDF thus maps to a region containing a number of cancer-related loci and thus must be considered a candidate gene for these cancers. Preliminary studies with cultured human Y79 retinoblastoma cells indicate that expression of PEDF is associated with relatively undifferentiated, proliferating cells rather than their differentiated, slow-growing counterparts. This and the fact that the PEDF protein can act as a potent neurotrophic differentiating agent suggest that PEDF is linked to proliferative events that terminate in final phenotypic determination within specific cell lineages. (C) 1994 Academic Press, Inc. C1 UNIV MICHIGAN,SCH MED,DEPT OPHTHALMOL,ANN ARBOR,MI 48105. UNIV MICHIGAN,SCH MED,DEPT HUMAN GENET,ANN ARBOR,MI 48105. RP TOMBRANTINK, J (reprint author), NEI,RETINAL CELL & MOLEC BIOL LAB,BLDG 6,ROOM 311,BETHESDA,MD 20892, USA. OI Swaroop, Anand/0000-0002-1975-1141 FU NEI NIH HHS [EY07961] NR 19 TC 52 Z9 57 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JAN 15 PY 1994 VL 19 IS 2 BP 266 EP 272 DI 10.1006/geno.1994.1057 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NA603 UT WOS:A1994NA60300009 PM 8188257 ER PT J AU ALLIKMETS, RL KASHUBA, VI PETTERSSON, B GIZATULLIN, R LEBEDEVA, T KHOLODNYUK, ID BANNIKOV, VM PETROV, N ZAKHARYEV, VM WINBERG, G MODI, W DEAN, M UHLEN, M KISSELEV, LL KLEIN, G ZABAROVSKY, ER AF ALLIKMETS, RL KASHUBA, VI PETTERSSON, B GIZATULLIN, R LEBEDEVA, T KHOLODNYUK, ID BANNIKOV, VM PETROV, N ZAKHARYEV, VM WINBERG, G MODI, W DEAN, M UHLEN, M KISSELEV, LL KLEIN, G ZABAROVSKY, ER TI NOTI LINKING CLONES AS A TOOL FOR JOINING PHYSICAL AND GENETIC MAPS OF THE HUMAN GENOME SO GENOMICS LA English DT Article ID RENAL-CELL CARCINOMA; VONHIPPEL-LINDAU DISEASE; CPG ISLANDS; HUMAN CHROMOSOME-3; JUMPING LIBRARIES; SEQUENCE-ANALYSIS; CYSTIC-FIBROSIS; LUNG-CANCER; SHORT ARM; DNA AB To study the connection among NotI linking clones, CpG islands, and genes, the sequence surrounding 143 NotI sites was determined. These NotI linking clones were isolated from human chromosome 3-specific libraries and contain an average C + G content of 65%. These clones represent sequence-tagged sites that can be positioned onto chromosome maps and used for generating a long-range NotI map of the human genome. A majority (about 90%) of these clones contain transcribed sequences, as detected by Northern blot hybridization, providing an efficient link between physical and functional (genetic) maps. The GenBank nucleotide database was searched with sequences from these NotI linking clones. For many clones, homology was found to human and other vertebrate genes. About 20 clones contained various repeats in their sequences and may represent microsatellite loci. Most of these NotI linking clones therefore represent evolutionarily conserved DNA fragments and also can be used for comparative genome mapping of other mammalian species. In addition, approximately 20% of all sequenced human CpG island-containing genes and more than 12% of all well-characterized human genes were found to possess NotI restriction sites. This is at least 2-5 times more than has been previously estimated and suggests that NotI sites have a much stronger association with genes. (C) 1994 Academic Press, Inc. C1 NCI,FCRDC,DYNCORP,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS & DEV P,FREDERICK,MD 21702. KAROLINSKA INST,DEPT TUMOR BIOL,S-10401 STOCKHOLM,SWEDEN. ROYAL INST TECHNOL,DEPT BIOCHEM & BIOTECHNOL,S-10044 STOCKHOLM,SWEDEN. VA ENGELHARDT MOLEC BIOL INST,MOSCOW 117984,RUSSIA. VECTOR INC,NOVOSIBIRSK,RUSSIA. KIEV MOLEC BIOL & GENET INST,KIEV 252627,UKRAINE. RP ALLIKMETS, RL (reprint author), NCI,FCRDC,DYNCORP,PROGRAM RESOURCES INC,VIRAL CARCINOGENESIS LAB,BLDG 560,ROOM 21-19,FREDERICK,MD 21702, USA. RI Zabarovsky, Eugene/A-6645-2010; Dean, Michael/G-8172-2012; Winberg, Gosta/I-5686-2013; OI Dean, Michael/0000-0003-2234-0631; Winberg, Gosta/0000-0002-3371-4056; Holodnuka, Irina/0000-0002-7208-4499 FU NCI NIH HHS [5 RO1 CA14054-15] NR 41 TC 43 Z9 43 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JAN 15 PY 1994 VL 19 IS 2 BP 303 EP 309 DI 10.1006/geno.1994.1062 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NA603 UT WOS:A1994NA60300014 PM 8188261 ER PT J AU ABE, T KIKUCHI, T SHINOHARA, T AF ABE, T KIKUCHI, T SHINOHARA, T TI THE SEQUENCE OF THE HUMAN PHOSDUCIN GENE (PDC) AND ITS 5'-FLANKING REGION SO GENOMICS LA English DT Note ID RETINOID-BINDING PROTEIN; ROD OUTER SEGMENTS; PINEAL-GLAND; TRANSGENIC MICE; CDNA; PHOSPHOPROTEIN; EXPRESSION; KINASE; BOVINE AB Phosducin, a principal protein of the retinal photoreceptor cells, modulates the phototransduction cascade by interacting with transducin. Recently, it has been reported that phosducin is a protein virtually identical to the G-protein inhibitor protein (GIP) in brain. Here, we have sequenced the complete human gene (PDC) and 2215 bp of its 5'-flanking region. The gene is 18 kb in length and has four exons and three introns. The splicing sites for donor and acceptor are in good agreement with the GT/AG rule. Comparative studies of human and mouse phosducin revealed highly homologous sequences. Both the human phosducin gene and a mutant gene locus for Usher syndrome type II have been assigned to chromosome 1q25-q32. The association of this gene with a human disease locus suggests that phosducin may be a potential candidate gene for this disorder. (C) 1994 Academic Press, Inc. C1 NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. OI Shinohara, Toshimichi/0000-0002-7197-9039 NR 23 TC 14 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JAN 15 PY 1994 VL 19 IS 2 BP 369 EP 372 DI 10.1006/geno.1994.1072 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NA603 UT WOS:A1994NA60300024 PM 8188267 ER PT J AU JENKINS, NA ROTHE, H GILBERT, DJ COPELAND, NG KOLB, H AF JENKINS, NA ROTHE, H GILBERT, DJ COPELAND, NG KOLB, H TI MAPPING OF THE GENE FOR INDUCIBLE NITRIC-OXIDE (NO) SYNTHASE OF MOUSE MACROPHAGES GO CHROMOSOME-11, CLOSE TO EVI-2, NU, AND IDD-4 SO GENOMICS LA English DT Note ID DIABETES-MELLITUS; CLONING; MAP C1 UNIV DUSSELDORF,DIABET RES INST,D-40225 DUSSELDORF,GERMANY. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL,BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 15 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JAN 15 PY 1994 VL 19 IS 2 BP 402 EP 404 DI 10.1006/geno.1994.1085 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NA603 UT WOS:A1994NA60300037 PM 7514570 ER PT J AU MAGRATH, IT AF MAGRATH, IT TI TARGETED APPROACHES TO CANCER-THERAPY - MEETING HELD AT STONE HOUSE, NIH, BETHESDA, MD, JANUARY 11-12, 1993 SO INTERNATIONAL JOURNAL OF CANCER LA English DT Editorial Material RP MAGRATH, IT (reprint author), NCI,PEDIAT BRANCH,LYMPHOMA BIOL SECT,BETHESDA,MD 20892, USA. NR 0 TC 31 Z9 31 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 15 PY 1994 VL 56 IS 2 BP 163 EP 166 DI 10.1002/ijc.2910560202 PG 4 WC Oncology SC Oncology GA MT121 UT WOS:A1994MT12100001 PM 7906250 ER PT J AU LEVINE, PH MANNS, A JAFFE, ES COLCLOUGH, G CAVALLARO, A REDDY, G BLATTNER, WA AF LEVINE, PH MANNS, A JAFFE, ES COLCLOUGH, G CAVALLARO, A REDDY, G BLATTNER, WA TI THE EFFECT OF ETHNIC-DIFFERENCES ON THE PATTERN OF HTLV-I-ASSOCIATED T-CELL LEUKEMIA-LYMPHOMA (HATL) IN THE UNITED-STATES SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID VIRUS; CLASSIFICATION; MALIGNANCIES; RISK AB Human T-cell lymphotropic virus Type I (HTLV-I) is the primary etiologic factor for adult T-cell leukemia/lymphoma (ATL). Although HTLV-I is endemic in Japan and the Caribbean islands, the reported clinical and epidemiologic features of ATL in these 2 parts of the world are quite different. ATL has been diagnosed at a younger age and is reported more frequently as the lymphomatous type rather than the acute type with leukemia in the Caribbean basin as compared with the presentation in Japan. In order to characterize ATL in the United States, a registry has been established at the National Cancer Institute for the purpose of recording all cases originally diagnosed in the United States. This registry was utilized to examine the effect of ethnic differences on age of onset and clinical features of ATL, using the same data base. Clinical and laboratory information was obtained from 177 patients suspected of having ATL, who were treated at the National Institutes of Health, or had biological samples sent for evaluation, or were reported in the literature. Histopathologic review and virologic studies were performed by standardized methods. Of 177 patients registered, 127 were considered as having ATL, according to an algorithm combining clinical, pathologic and laboratory features. Presenting features in the confirmed cases consisted primarily of lymphadenopathy (76.6%), hypercalcemia (72.5%), leukemia (82%), skin involvement (48.2%) and hepatomegaly (53.6%). Patients of Japanese ancestry were generally older (median age 63, range 51 to 73 years) than patients of African-American descent (median age 39, range 7 to 75 years) and presented more often with leukemia (90 vs. 69%). Of the 103 cases where country of birth was confirmed, 45 (43.7%) were born in the United States. The prognosis was generally poor (median survival 3.24 months), but rare long-term remissions were documented. (C) 1994 Wiley-Liss, Inc.* C1 RES TRIANGLE INST,ROCKVILLE,MD 20892. RP LEVINE, PH (reprint author), NCI,EPN 434,BETHESDA,MD 20892, USA. NR 24 TC 19 Z9 19 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 15 PY 1994 VL 56 IS 2 BP 177 EP 181 DI 10.1002/ijc.2910560205 PG 5 WC Oncology SC Oncology GA MT121 UT WOS:A1994MT12100004 PM 8314298 ER PT J AU SAWAYA, R TOFILON, PJ MOHANAM, S ALIOSMAN, F LIOTTA, LA STETLERSTEVENSON, WG RAO, JS AF SAWAYA, R TOFILON, PJ MOHANAM, S ALIOSMAN, F LIOTTA, LA STETLERSTEVENSON, WG RAO, JS TI INDUCTION OF TISSUE-TYPE PLASMINOGEN-ACTIVATOR AND 72-KDA TYPE-IV COLLAGENASE BY IONIZING-RADIATION IN RAT ASTROCYTES SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID CELLS; BRAIN; FIBROBLASTS; GROWTH; GENE AB Radiation-induced damage in the central nervous system (CNS) is believed to be targeted to glial or endothelial cells or both, although the pathophysiology of the process is still poorly understood. In this study, we irradiated rat astrocytes with single doses of X-rays and then estimated the levels of tissue plasminogen activator (tPA) and collagenase in serum-free medium and cell extracts at different times. Fibrin zymography revealed increased levels of intracellular tPA activity at 12 hr after irradiation. Gelatin zymography showed continuously increasing levels of extracellular 72-kDa type-IV collagenase after irradiation. Quantitative enzymatic activities by densitometry showed a 3- to 4-fold elevation in the level of the intracellular tPA activity at 12 hr and a 5- to 6-fold increase in the level of the extracellular 72-kDa type-IV collagenase activity at 48 hr. An ELISA with specific antibodies for tPA and 72-kDa type-IV collagenase indicated a 5-fold increase in the level of tPA at 12 hr and a more-than-7-fold increase in the level of 72-kDa type-IV collagenase at 48 hr. This study adds considerable credibility to the proposed role of plasminogen activators and type-IV collagenase in the development of CNS damage after radiotherapy for brain tumors. (C) 1994 Wiley-Liss, Inc. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT NEUROSURG,BOX 064,1515 HOLCOMBE BLVD,HOUSTON,TX 77025. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT EXPTL RADIOTHERAPY,HOUSTON,TX 77025. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT EXPTL PEDIAT,HOUSTON,TX 77025. NCI,PATHOL LAB,BETHESDA,MD 20892. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 FU NCI NIH HHS [CA-06294, NCI CA-16672] NR 24 TC 40 Z9 40 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 15 PY 1994 VL 56 IS 2 BP 214 EP 218 DI 10.1002/ijc.2910560212 PG 5 WC Oncology SC Oncology GA MT121 UT WOS:A1994MT12100011 PM 8314304 ER PT J AU PIERCE, LJ MERINO, MJ DANGELO, T BARKER, EA GILBERT, L COWAN, KH STEINBERG, SM GLATSTEIN, E AF PIERCE, LJ MERINO, MJ DANGELO, T BARKER, EA GILBERT, L COWAN, KH STEINBERG, SM GLATSTEIN, E TI IS C-ERB B-2 A PREDICTOR FOR RECURRENT DISEASE IN EARLY-STAGE BREAST-CANCER SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE BREAST CANCER; C-ERB B-2 AMPLIFICATION; PROTEIN OVER-EXPRESSION ID HER-2 NEU ONCOGENE; S-PHASE FRACTION; PROGNOSTIC-SIGNIFICANCE; PROTEIN OVEREXPRESSION; C-ERBB-2 AMPLIFICATION; EXPRESSION; CARCINOMA; INSITU; ASSOCIATION; SURVIVAL AB Purpose: To assess the prognostic importance of c-erb B-2 expression in early stage breast cancer. Methods and Materials: Immunohistochemical analysis for c-erb B-2 over-expression was retrospectively performed on 107 paraffin-embedded specimens of women with Stage I or II breast cancer entered in a randomized trial. Results were correlated with known prognostic factors such as pathologic axillary involvement, T-size, estrogen and progesterone receptor status, and nuclear grade. Immunohistochemical staining for c-erb B-2 protein expression was also correlated with breast/chest wall failure as well as survival without evidence of disease (NED) and overall survival. Results: C-erb B-2 overexpression was positive in 21% of the biopsy specimens. A significant association was found between c-erb-2 positivity and lesions containing an intraductal component, with 62% of lesions staining positively for c-erb B-2 having an intraductal component compared to only 36% of lesions with an intraductal component staining negatively for the c-erb B-2 protein (p2 = .031). A significant correlation between c-erb B-2 protein overexpression and axillary nodal status, primary tumor size, nuclear grade, and estrogen and progesterone receptor status was not identified. Cox proportional hazards model did not show a significant effect of c-erb B-2 expression for NED or overall survival. Conclusion: Our study did not find over-expression of c-erb B-2 to reliably predict for recurrent disease in early stage breast cancer. This data can be added to other series comparing erb B-2 expression and disease outcome among node-positive and node-negative women with carcinoma of the breast. C1 NCI,MED BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. MOLEC ONCOL INC,GAITHERSBURG,MD 20878. UNIV TEXAS,SW MED SCH,DEPT RADIAT ONCOL,DALLAS,TX 75235. NCI,PATHOL LAB,BETHESDA,MD 20892. RP PIERCE, LJ (reprint author), NCI,RADIAT ONCOL BRANCH,BLDG 10 B3B69,BETHESDA,MD 20892, USA. NR 32 TC 17 Z9 18 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN 15 PY 1994 VL 28 IS 2 BP 395 EP 403 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA MP981 UT WOS:A1994MP98100009 PM 7903962 ER PT J AU BACIK, I COX, JH ANDERSON, R YEWDELL, JW BENNINK, JR AF BACIK, I COX, JH ANDERSON, R YEWDELL, JW BENNINK, JR TI TAP (TRANSPORTER ASSOCIATED WITH ANTIGEN PROCESSING)-INDEPENDENT PRESENTATION OF ENDOGENOUSLY SYNTHESIZED PEPTIDES IS ENHANCED BY ENDOPLASMIC-RETICULUM INSERTION SEQUENCES LOCATED AT THE AMINO-TERMINUS BUT NOT CARBOXYL-TERMINUS OF THE PEPTIDE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; TOXIC LYMPHOCYTES-T; CLASS-I MOLECULES; HLA-B ANTIGENS; DOCKING PROTEIN; MHC MOLECULES; RMA-S; CELLS; EXPRESSION; RECOGNITION AB Under most circumstances, cell surface MHC class I molecules display peptides derived from a cytosolic pool of proteins. The efficient presentation of such peptides requires the functioning of two MHC gene products [TAP1 and TAP2 (transporter-associated with Ag processing 1 and 2)] that form a complex that facilitates transmembrane movement of peptides from the cytosol to the endoplasmic reticulum, the site of peptide association with class I molecules. It has been previously shown that peptides can be presented in a TAP-independent manner in association with HLA A2.1 or H-2 K(d) if they are expressed COOH-terminal to an endoplasmic reticulum insertion/signal sequence derived from the adenovirus E3/19K glycoprotein (Anderson et al., 1991. J. Exp. Med. 174: 489; Eisenlohr et al., 1992. Cell 71: 963). We show that: 1) the E3/1 9K signal sequence greatly enhances the presentation of each of four additional peptides tested in association with H-2 K(b) or K(k), 2) the E3/19K signal sequence can be substituted by a signal sequence derived from beta-IFN, and 3) the E3/19K signal sequence does not function when located at the COOH terminus of antigenic peptides. These findings indicate that first, many peptides require TAP for efficient presentation to T cells, second, expression of peptides COOH-terminal to signal sequences is a generally applicable method of bypassing the TAP-dependence of peptide presentation and third, the leader sequence does not act to bypass TAP simply by increasing the hydrophobic nature of peptides. C1 NIAID,VIRAL DIS LAB,CELLULAR BIOL SECT,BETHESDA,MD 20892. RP BACIK, I (reprint author), NIAID,VIRAL DIS LAB,VIRAL IMMUNOL SECT,BLDG 4,BETHESDA,MD 20892, USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 51 TC 127 Z9 129 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 JAN 15 PY 1994 VL 152 IS 2 BP 381 EP 387 PG 7 WC Immunology SC Immunology GA MR216 UT WOS:A1994MR21600001 PM 8283027 ER PT J AU NORIHISA, Y MCVICAR, DW GHOSH, P HOUGHTON, AN LONGO, DL CREEKMORE, SP BLAKE, T ORTALDO, JR YOUNG, HA AF NORIHISA, Y MCVICAR, DW GHOSH, P HOUGHTON, AN LONGO, DL CREEKMORE, SP BLAKE, T ORTALDO, JR YOUNG, HA TI INCREASED PROLIFERATION, CYTOTOXICITY, AND GENE-EXPRESSION AFTER STIMULATION OF HUMAN PERIPHERAL-BLOOD T-LYMPHOCYTES THROUGH A SURFACE GANGLIOSIDE (GD3) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; CELL ANTIGEN RECEPTOR; NATURAL-KILLER-CELLS; MONOCLONAL-ANTIBODIES; TYROSINE PHOSPHORYLATION; INTERLEUKIN-2 RECEPTOR; MEDIATED MODULATION; ACTIVATION; RESPONSES; MELANOMA AB Previous studies have suggested that gangliosides have an important role in cell signaling and recognition. However, their specific function in these processes has not been clearly defined. A mAb, R24, that reacts specifically with a cell surface ganglioside (GD3) has been demonstrated to stimulate proliferation of T cells derived from human peripheral blood. In this study, we have investigated the mechanisms by which the R24 mAb affects T cell functions. We have observed that the R24 mAb stimulates GD3+ T cell proliferation, cytotoxicity, and surface marker expression of IL-2R alpha-chain, IL-2R beta-chain, HLA-DR, CD11a, and CD11c. Additionally, IFN-gamma activity but not IL-1, IL-2, or IL-4 activity was present in culture supernatants 72 h after R24 stimulation. In some donors, increased IL-6 and TNF-alpha activity also was detected after R24 treatment. Furthermore, R24 treatment resulted in translocation of c-rel, but little or no NFkappaB p50 or p65, from the cytoplasm to the nucleus and an increase of NFkappaB binding complexes containing c-rel and p50. This treatment also caused increased tyrosine phosphorylation of specific protein substrates. R24-stimulated increases in proliferation, cytotoxicity, and cell surface protein expression could be blocked by cyclosporin and staurosporin, indicating that cyclophilin/calcineurin and protein kinase C may be involved in the R24 signaling pathway. Additionally, herbimycin A, a tyrosine kinase inhibitor, blocked the R24-stimulated increase in proliferation but not cytotoxicity at concentrations consistent with specificity for tyrosine kinases. These results suggest that multiple biochemical pathways are involved in the activation of human T cells by R24. C1 NCI,FCRDC,PRI DYNCORP,BRMP,EXPTL IMMUNOL LAB,BLDG 50,ROOM 31-93,FREDERICK,MD 21702. NCI,FCRDC,PRI DYNCORP,BIOL RESPONSE MODIFIERS PROGRAM,BIOL RESOURCES BRANCH,FREDERICK,MD 21702. NCI,FCRDC,PRI DYNCORP,BIOL RESPONSE MODIFIERS PROGRAM,CLIN RES BRANCH,FREDERICK,MD 21702. NCI,FCRDC,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. RI McVicar, Daniel/G-1970-2015 NR 27 TC 45 Z9 45 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 JAN 15 PY 1994 VL 152 IS 2 BP 485 EP 495 PG 11 WC Immunology SC Immunology GA MR216 UT WOS:A1994MR21600013 PM 8283032 ER PT J AU SHIRAI, M PENDLETON, CD AHLERS, J TAKESHITA, T NEWMAN, M BERZOFSKY, JA AF SHIRAI, M PENDLETON, CD AHLERS, J TAKESHITA, T NEWMAN, M BERZOFSKY, JA TI HELPER-CYTOTOXIC T-LYMPHOCYTE (CTL) DETERMINANT LINKAGE REQUIRED FOR PRIMING OF ANTI-HIV CD8+ CTL IN-VIVO WITH PEPTIDE VACCINE CONSTRUCTS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; FREE SYNTHETIC PEPTIDE; CLASS-I; CELL RESPONSES; ENVELOPE; MHC; ANTIBODIES; PROTECTION; INDUCTION; INVITRO AB CTL are a critical component of protective immunity against viral infections, but requirements for in vivo priming of CTL are not completely understood. Covalent linkage of a helper determinant to a CTL determinant, analogous to that required for cognate help for antibody production, does not appear to be necessary in vitro, but its necessity has not been extensively explored in vivo, especially at a molecular level. We previously defined peptides encompassing multideterminant regions of HIV-1 gp160 (cluster peptides) recognized by Th from mice and humans of multiple MHC types. To investigate the requirement for Th in the development of CTL in vivo, in the context of developing a synthetic peptide vaccine for HIV active in multiple strains of mice, we immunized with compound peptides representing an immunodominant CTL epitope, P18, of gp160, co-linearly synthesized at the C-terminus of three cluster peptides. Spleen cells from compound-peptide-immunized mice of three MHC haplotypes sharing the D(d) class I MHC molecule but with different class II molecules exhibited enhanced gp160-specific CD8+ CTL activity and CD4+ Th. In contrast, immunization with P18 alone or a mixture of cluster peptide and P18 elicited only marginal CTL activity. These results imply a requirement for determinant linkage in CTL induction in vivo similar to that already well recognized for cognate help for antibody induction. The results also define promising peptide HIV vaccine candidates for induction of CTL, as well as neutralizing antibodies, in diverse MHC types. C1 NCI,METAB BRANCH,MOLEC IMMUNOGENET & VACCINE RES SECT,BLDG 10,ROOM 6B-12,BETHESDA,MD 20892. CAMBRIDGE BIOTECH,WORCESTER,MA 01605. NR 50 TC 149 Z9 152 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 JAN 15 PY 1994 VL 152 IS 2 BP 549 EP 556 PG 8 WC Immunology SC Immunology GA MR216 UT WOS:A1994MR21600019 PM 8283036 ER PT J AU DIBRINO, M PARKER, KC SHILOACH, J TURNER, RV TSUCHIDA, T GARFIELD, M BIDDISON, WE COLIGAN, JE AF DIBRINO, M PARKER, KC SHILOACH, J TURNER, RV TSUCHIDA, T GARFIELD, M BIDDISON, WE COLIGAN, JE TI ENDOGENOUS PEPTIDES WITH DISTINCT AMINO-ACID ANCHOR RESIDUE MOTIFS BIND TO HLA-A1 AND HLA-B8 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID VIRUS MATRIX PEPTIDE; CLASS-I MOLECULE; ANTIGEN PRESENTATION; ESCHERICHIA-COLI; LYMPHOCYTE-T; SEQUENCE; COMPLEX; RECOGNITION; CONFORMATION; POLYMORPHISM AB Distinct amino acid (aa) residue motifs for peptides binding to HLA-A1 and HLA-B8 were identified by sequence analyses of reversed-phase HPLC fractions containing endogenous peptides derived from these HLA molecules. Fifteen different primary sequences were determined for HLA-A1-associated peptides, 12 of which were nine aa in length. Common features among these peptide sequences were Tyr at the COOH-terminus, a negatively charged aa (usually Glu) at position 3 (P3), and Pro at P4. Twenty-seven different primary sequence assignments were made for HLA-B8-associated peptides, most of which were eight aa in length. Lys, and in a few cases Arg, predominated at P3 and P5; Leu and Pro predominated at P2, and Leu was the preferred COOH-terminal residue. Unlike all other human class I molecules whose peptide-binding properties have been studied, both HLA-A1 and HLA-B8 endogenous peptide sequences have a dominant anchor residue at P3, and these aa are opposite in charge to the aa at position 156 of the peptide-binding site. Synthetic peptides corresponding to endogenous peptide sequences bound to their respective HLA molecules in vitro, indicating that they derive from peptides bound to HLA and not from copurifying contaminants. Eight of the HLA-A1 and HLA-B8 endogenous peptide sequences matched intracellularly expressed proteins found in protein sequence data bases. The HLA-A1 peptide-binding motif was then used to identify potential antigenic peptides from influenza A viral proteins that bound to HLA-A1 in vitro. C1 NIAID,BIOL RESOURCES BRANCH,BLDG 4,ROOM 413,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NIDDKD,CELLULAR & DEV BIOL LAB,BETHESDA,MD. NINCDS,MOLEC IMMUNOL SECT,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. OI Parker, Kenneth/0000-0002-6282-2478 NR 41 TC 81 Z9 81 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 JAN 15 PY 1994 VL 152 IS 2 BP 620 EP 631 PG 12 WC Immunology SC Immunology GA MR216 UT WOS:A1994MR21600026 PM 7506728 ER PT J AU DAERON, M MALBEC, O BONNEROT, C LATOUR, S SEGAL, DM FRIDMAN, WH AF DAERON, M MALBEC, O BONNEROT, C LATOUR, S SEGAL, DM FRIDMAN, WH TI TYROSINE-CONTAINING ACTIVATION MOTIF-DEPENDENT PHAGOCYTOSIS IN MAST-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FC-GAMMA-RIII; AFFINITY IGE RECEPTOR; ANTIGEN PRESENTATION; IMMUNOGLOBULIN-E; EPSILON-RI; MACROPHAGE; ANTIBODY; SUBUNIT; ALPHA; IDENTIFICATION AB FcR capable of triggering cell activation share with BCR and TCR a conserved intracytoplasmic tyrosine-containing activation motif (TAM). Besides cell activation, these receptors trigger other biologic responses, such as endocytosis of soluble ligands. Murine mast cells express two types of FcR that, when aggregated by antibodies and multivalent Ag, trigger the release of inflammatory mediators and cytokines. These are high affinity receptors for IgE (FCepsilonRI) and low affinity receptors for IgG (FcgammaRIII). They comprise each an IgE- or IgG-binding alpha-subunit and two TAM-containing subunits that associate with both receptors: a beta-subunit and a homodimeric gamma-subunit that can associate also with the other subunits of the TCR. Herein, we focused on biologic activities triggered in mast cells via the TAM of the gamma-subunits. Using rat basophilic leukemia (RBL) cells stably transfected with cDNA-encoding murine FcRIIIalpha, we found that murine FcgammaRIII trigger the phagocytosis of antibody-coated erythrocytes. Using RBL transfectants expressing FcgammaRIII with a deletion of the intracytoplasmic domain of FcgammaRIIIalpha or chimeric receptors having the extracellular and transmembrane domains of FcgammaRII and the intracytoplasmic domain of FcgammaRIIIalpha, we showed that intracytoplasmic sequences of FcgammaRIIIalpha are neither necessary nor sufficient for FcgammaRIII to trigger phagocytosis. Using RBL transfectants expressing chimeric receptors having the extracellular and transmembrane domains of FcgammaRII and the TAM-containing intracytoplasmic domain of murine FcgammaRIIIgamma, we demonstrated that intracytoplasmic sequences of FcgammaRIIIgamma are sufficient to trigger phagocytosis. Using RBL transfectants expressing the same FcgammaRIIIgammma chimeras, in the TAM of which one, the other, or both tyrosine residues were mutated, we established that tyrosines in the TAM sequence are required for phagocytosis. Our results endow TAMgamma with previously unknown triggering capacities and FcgammaRIII with new biologic properties. C1 NCI,EXPTL IMMUNOL BRANCH,IMMUNE TARGETING SECT,BETHESDA,MD 20892. RP DAERON, M (reprint author), INST CURIE,IMMUNOL CELLULAIRE & CLIN LAB,INSERM,U255,26 RUE ULM,F-75005 PARIS,FRANCE. NR 46 TC 40 Z9 41 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 1994 VL 152 IS 2 BP 783 EP 792 PG 10 WC Immunology SC Immunology GA MR216 UT WOS:A1994MR21600043 PM 8283051 ER PT J AU SPURNEY, RF IBRAHIM, S BUTTERLY, D KLOTMAN, PE SANFILIPPO, F COFFMAN, TM AF SPURNEY, RF IBRAHIM, S BUTTERLY, D KLOTMAN, PE SANFILIPPO, F COFFMAN, TM TI LEUKOTRIENES IN RENAL-TRANSPLANT REJECTION IN RATS - DISTINCT ROLES FOR LEUKOTRIENE-B(4) AND PEPTIDOLEUKOTRIENES IN THE PATHOGENESIS OF ALLOGRAFT INJURY SO JOURNAL OF IMMUNOLOGY LA English DT Article ID POTENT; RELEVANCE; CELLS; BIOSYNTHESIS; INFLAMMATION; NEUTROPHILS; METABOLITES; LEUKOCYTES; KIDNEY AB To investigate the role of leukotrienes in renal allograft rejection, we studied the effects of specific leukotriene inhibitors in a rat kidney transplant model. The enhanced renal production of leukotrienes observed in allograft recipients was reduced in a dose-dependent manner by the specific 5-lipoxygenase inhibitor MK886. This suppression of leukotriene production caused a substantial improvement in renal function. Inhibition of 5-lipoxygenase also reduced the severity of vascular inflammation and endothelial injury in allografts, and profoundly inhibited expression of donor MHC class II Ag on kidney cells. Survival of renal allograft recipients was prolonged from 10 +/- 1 days in controls to 16 +/- 1 days in animals that received a 6-day course of MK886 (p < 0.05). To investigate the relative roles of LTB4 compared to peptidoleukotrienes in these processes, we treated a separate group of animals with the specific peptidoleukotriene receptor antagonist SKF106203. This agent inhibits the interaction of peptidoleukotrienes with their receptor(s) but does not affect the biologic actions of LTB4. In these studies, SKF106203 caused a modest improvement in renal allograft function that was of lesser magnitude than that seen with the 5-lipoxygenase inhibitor. SKF106203 also reduced vascular inflammation in allografts, but had no effect on expression of MHC class II Ag. We conclude that leukotrienes play a key role in the pathogenesis of renal allograft rejection. Furthermore, the detrimental effects of leukotrienes in rejection are mediated by distinct actions of LTB4 and peptidoleukotrienes. C1 VET ADM MED CTR,ROOM B3002 NEPHROL 111I,508 FULTON ST,DURHAM,NC 27705. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. DUKE UNIV,MED CTR,TRANSPLANTAT LAB,DURHAM,NC 27710. NIDR,LDB,MOLEC MED SECT,BETHESDA,MD 20892. FU NIDDK NIH HHS [P01-DK38108] NR 37 TC 40 Z9 40 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 JAN 15 PY 1994 VL 152 IS 2 BP 867 EP 876 PG 10 WC Immunology SC Immunology GA MR216 UT WOS:A1994MR21600053 PM 8283057 ER PT J AU CASPI, RR CHAN, CC GRUBBS, BG SILVER, PB WIGGERT, B PARSA, CF BAHMANYAR, S BILLIAU, A HEREMANS, H AF CASPI, RR CHAN, CC GRUBBS, BG SILVER, PB WIGGERT, B PARSA, CF BAHMANYAR, S BILLIAU, A HEREMANS, H TI ENDOGENOUS SYSTEMIC IFN-GAMMA HAS A PROTECTIVE ROLE AGAINST OCULAR AUTOIMMUNITY IN MICE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERFERON-GAMMA; INDUCED ARTHRITIS; STRAIN VARIATION; UVEORETINITIS; INDUCTION; INVIVO; ANTIBODY; INVITRO; EXPRESSION; RESISTANCE AB Locally produced IFN-gamma has been implicated in enhancing inflammation and in promoting organ-specific autoimmunity. In the present study, we investigated the influence of systemically available IFN-gamma on the expression of experimental autoimmune uveoretinitis (EAU) induced in mice with the retinal Ag, interphotoreceptor retinoid binding protein (IRBP). EAU-susceptible B10.A mice treated with a mAb to IFN-gamma developed much more severe EAU than did the controls and had increased delayed hypersensitivity (DH) responses to IRBP. There was an increase in the proportion of macrophage/monocytes vs lymphocytes in the ocular lesions of treated animals. The anti-IFN-gamma treatment did not prevent expression of MHC class II within the ocular tissues. Conversely, treatment with rIFN-gamma ameliorated EAU expression and lowered DH responses. This occurred despite widespread induction of MHC class II Ag in the ocular tissues and other organs. In contrast to EAU and DH, serum antibody titers and lymphocyte proliferation to IRBP were not significantly affected by either treatment. Experiments in several genetically resistant strains of mice showed that treatment with anti-IFN-gamma was able to up-regulate disease expression also in some EAU-resistant strains. In the case of one such strain, resistance to EAU induction was completely abrogated by the treatment. We conclude that endogenously produced IFN-gamma at the systemic level acts to down-regulate EAU in the mouse and that IFN-gamma-related mechanisms may be involved in conferring resistance to EAU in some mouse genotypes. C1 CATHOLIC UNIV LEUVEN,REGA INST MED RES,SCH MED,IMMUNOBIOL LAB,B-3000 LOUVAIN,BELGIUM. RP CASPI, RR (reprint author), NEI,IMMUNOL LAB,BLDG 10,ROOM 10N222,BETHESDA,MD 20892, USA. NR 40 TC 114 Z9 116 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 1994 VL 152 IS 2 BP 890 EP 899 PG 10 WC Immunology SC Immunology GA MR216 UT WOS:A1994MR21600055 PM 8283058 ER PT J AU NAM, JM AF NAM, JM TI SAMPLE-SIZE REQUIREMENTS FOR STRATIFIED PROSPECTIVE STUDIES WITH NULL HYPOTHESIS OF NON-UNITY RELATIVE RISK USING THE SCORE TEST SO STATISTICS IN MEDICINE LA English DT Article ID APPROXIMATE INTERVAL ESTIMATION; BINOMIAL PARAMETERS; DIFFERENCE; SKEWNESS; TABLES; RATIO; JAPAN AB The standard test of the null hypothesis of unity of the relative risk seeks to determine if two treatments differ. It does not apply when the requirement is either to establish the equivalence of two treatments or to determine whether the relative risk is less than a specified value other than one. This paper presents the asymptotic power function of the score test for the null hypothesis of a specified value of a common relative risk for stratified prospective studies and proposes an approximate formula for the sample size required for a specific power of the test. One can obtain a sample size formula for stratified studies with the standard null hypothesis of unity relative risk as a special case of this formula. RP NAM, JM (reprint author), NCI,BIOSTAT BRANCH,6130 EXECUT BLVD,EPN-403,ROCKVILLE,MD 20892, USA. NR 17 TC 5 Z9 5 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 15 PY 1994 VL 13 IS 1 BP 79 EP 86 DI 10.1002/sim.4780130109 PG 8 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA MP260 UT WOS:A1994MP26000007 PM 9061842 ER PT J AU RUSSEKCOHEN, E SIMON, RM AF RUSSEKCOHEN, E SIMON, RM TI SELECTING THE BEST DOSE WHEN A MONOTONIC DOSE-RESPONSE RELATION EXISTS SO STATISTICS IN MEDICINE LA English DT Article ID TRIAL AB We propose a method for selecting the best treatment when a monotonic dose response relationship exists. Because of side effects associated with higher doses, the highest dose may not be the optimum, particularly when a lower dose gives a similar response. Rather than assume a particular functional relationship of dose to response, we use isotonic regression techniques. We consider the case of three treatment levels, which is applicable to many clinical trials. The lowest treatment level may represent a placebo or no treatment control. While we focus primarily on Bernoulli response variables, we also discuss a model for normally distributed data. We suggest a two-stage procedure that we have investigated via simulation. C1 NCI,BIOMETR RES BRANCH,BETHESDA,MD 20892. RP RUSSEKCOHEN, E (reprint author), UNIV MARYLAND,DEPT ANIM SCI,COLL PK,MD 20742, USA. NR 13 TC 4 Z9 4 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 15 PY 1994 VL 13 IS 1 BP 87 EP 95 DI 10.1002/sim.4780130110 PG 9 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 MP260 UT WOS:A1994MP26000008 PM 9061843 ER PT J AU CITRON, BA DAVIS, MD KAUFMAN, S AF CITRON, BA DAVIS, MD KAUFMAN, S TI ELECTROSTATIC ACTIVATION OF RAT PHENYLALANINE-HYDROXYLASE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ESCHERICHIA-COLI; LIVER; PHOSPHORYLATION; STIMULATION; INVIVO; PURIFICATION; SEQUENCE; PROTEIN RP CITRON, BA (reprint author), NIMH,NEUROCHEM LAB,RM 3D30,BLDG 36,BETHESDA,MD 20892, USA. NR 33 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 14 PY 1994 VL 198 IS 1 BP 174 EP 180 DI 10.1006/bbrc.1994.1025 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MQ932 UT WOS:A1994MQ93200025 PM 7904815 ER PT J AU KHARBANDA, S SALEEM, A EMOTO, Y STONE, R RAPP, U KUFE, D AF KHARBANDA, S SALEEM, A EMOTO, Y STONE, R RAPP, U KUFE, D TI ACTIVATION OF RAF-1 AND MITOGEN-ACTIVATED PROTEIN-KINASES DURING MONOCYTIC DIFFERENTIATION OF HUMAN MYELOID-LEUKEMIA CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COLONY-STIMULATING FACTOR; TUMOR NECROSIS FACTOR; C-JUN EXPRESSION; GROWTH-FACTOR; OKADAIC ACID; MAP KINASE; GENE-EXPRESSION; FOS GENE; MOLECULAR-CLONING; INDUCTION AB Treatment of human myeloid leukemia cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C (PKC), is associated with induction of monocytic differentiation. Since PKC can act immediately upstream to the cytoplasmic Raf-1 serine/threonine protein kinase, we studied activation of Raf-1 during induction of the differentiated monocytic phenotype. The results demonstrate that Raf-1 is activated during TPA-induced monocytic differentiation of HL-60 cells. In contrast, there was little effect of TPA on this kinase in an HL-60 variant, designated HL-525, which is resistant to TPA-induced differentiation. Treatment of both HL-60 and HL-525 cells with okadaic acid, an inhibitor of serine/threonine protein phosphatases 1 and 2A, was associated with Raf-1 activation and induction of the monocytic phenotype. Since Raf-1 can activate the mitogen-activated protein (MAP) kinases, we also studied the relationship between MAP kinase activation and monocytic differentiation. Treatment of HL-60, but not HL-525, cells with TPA was associated with increased MAP kinase activity as determined by phosphorylation of myelin basic protein and the c-Jun Y peptide. Okadaic acid-induced differentiation of both HL-60 and HL-525 cells was similarly accompanied by increases in MAP kinase activity. These findings indicated that activation of Raf-1/MAP kinase signaling is associated with induction of a differentiated monocytic phenotype and that okadaic acid by-passes a defect in this cascade in TPA-treated HL-525 cells. While recent studies have shown that HL-525 cells are deficient in PKCbeta, the present results demonstrate that PKCbeta expression is up-regulated in the HL-525 variant by treatment with retinoic acid. The results also demonstrate that retinoic acid-treated HL-525 cells respond to TPA with activation of Raf-1 and MAP kinase, as well as induction of monocytic differentiation. Taken together, the results indicate that activation of Raf-1/MAP kinase signaling is associated with monocytic differentiation and that stimulation of serine/threonine protein phosphorylation by TPA or okadaic acid is sufficient for reversal of the leukemic HL-60 phenotype. C1 NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. RP KHARBANDA, S (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CLIN PHARMACOL LAB,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA42802] NR 56 TC 110 Z9 110 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 14 PY 1994 VL 269 IS 2 BP 872 EP 878 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR220 UT WOS:A1994MR22000019 PM 8288641 ER PT J AU BERGSTEN, P MOURA, AS ATWATER, I LEVINE, M AF BERGSTEN, P MOURA, AS ATWATER, I LEVINE, M TI ASCORBIC-ACID AND INSULIN-SECRETION IN PANCREATIC-ISLETS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALPHA-AMIDATING MONOOXYGENASE; BETA-CELL; VITAMIN-C; DEHYDROASCORBIC ACID; DIABETES-MELLITUS; HUMAN NEUTROPHILS; CHROMAFFIN CELLS; RAT PANCREAS; HUMAN-PLASMA; GLUCOSE AB The effect of ascorbic acid on glucose-induced insulin release from single pancreatic islets was measured using a new, ultra-sensitive enzyme-linked immunosorbent insulin assay. Within 20 s ascorbic acid inhibited insulin secretion; inhibition was dose dependent and completely reversible. There was a 50% inhibition of the secretory response with 200 muM ascorbic acid and 90% inhibition with 400 muM ascorbic acid. The decrease in insulin secretion was recorded as a reduction of the amplitudes of the fast insulin transients, which give rise to the oscillatory nature of insulin secretion. The inhibition of glucose-induced insulin release by ascorbic acid was associated with hyperpolarization of the pancreatic beta-cell. Suppression of glucose-induced membrane depolarization was evident after 20 s, was dose dependent, and was completely reversible. The data here may provide the first explanation of why plasma ascorbate concentrations are tightly controlled. C1 NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892. NR 49 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 14 PY 1994 VL 269 IS 2 BP 1041 EP 1045 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR220 UT WOS:A1994MR22000043 PM 8288558 ER PT J AU WENTHOLD, RJ TRUMPY, VA ZHU, WS PETRALIA, RS AF WENTHOLD, RJ TRUMPY, VA ZHU, WS PETRALIA, RS TI BIOCHEMICAL AND ASSEMBLY PROPERTIES OF GLUR6 AND KA2, 2 MEMBERS OF THE KAINATE RECEPTOR FAMILY, DETERMINED WITH SUBUNIT-SPECIFIC ANTIBODIES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACID BINDING-SITES; SELECTIVE GLUTAMATE RECEPTORS; HIGH-AFFINITY KAINATE; RAT-BRAIN; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; NERVOUS-SYSTEM; NMDA RECEPTOR; CHANNELS; AMPA AB To examine subunit assembly and biochemical properties of two members of the kainate family of glutamate receptors (GluR), antibodies were made to synthetic peptides corresponding to the carboxyl termini of GluR6 and KA2. lmmunoblot analysis of membranes from human embryonic kidney cells transfected with glutamate receptor cDNAs showed that these antibodies are selective for their respective receptor subunit except that the antibody to GluR6 also recognizes GluR7, which is expected due to the sequence homology between the two subunits at the carboxyl terminus. In transfected cell membranes, immunoblot analysis with the antibody to GluR6 showed a major immunoreactive band at 118 kDa and minor bands at 103 and 28 kDa. The 103-kDa band appears to be a deglycosylated form of GluR6 since deglycosylation eliminates staining at 118 kDa and increases staining of the 103-kDa band. lmmunoblot analysis of KA2 transfected cell membranes shows a major band at 123 kDa and minor bands at 109 and 37 kDa. Deglycosylation converts the 123-kDa band into a 109-kDa. band. Analysis of brain tissues shows that both antibodies label single major bands which migrate at the same molecular masses as those from transfected cell membranes, 118 and 123 kDa for GluR6 and KA2, respectively. lmmunoprecipitation studies showed that antibodies to GluR6 and KA2 selectively immunoprecipitated [H-3]kainate binding activity, but not H-3-labeled alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) binding activity, from Triton X-100-solubilized rat brain membranes. Furthermore, each antibody co-immunoprecipitated GluR6 and KA2 from cells co-transfected with GluR6 and KA2 cDNAs and from detergent-solubilized rat brain membranes, indicating that these two subunits can coassemble into a molecular complex. Interestingly, GluR1 and GluR2, subunits of the AMPA receptor, also co-immunoprecipitated with GluR6 in cells co-transfected with GluR6 and GluR1 or GluR2 cDNAs. Such complexes appear to be present to a limited extent in the brain. RP WENTHOLD, RJ (reprint author), NIH,NATL INST DEAFNESS & COMMUN DIS,NEUROCHEM LAB,BLDG 36,RM 5D08,BETHESDA,MD 20892, USA. NR 37 TC 102 Z9 102 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 14 PY 1994 VL 269 IS 2 BP 1332 EP 1339 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR220 UT WOS:A1994MR22000088 PM 8288598 ER PT J AU WEISZ, A ANDRZEJEWSKI, D HIGHET, RJ ITO, Y AF WEISZ, A ANDRZEJEWSKI, D HIGHET, RJ ITO, Y TI PREPARATIVE SEPARATION OF COMPONENTS OF THE COLOR ADDITIVE FD-AND-C RED NO-3 (ERYTHROSINE) BY PH-ZONE-REFINING COUNTERCURRENT CHROMATOGRAPHY SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 10th International Symposium on Preparative Chromatography CY JUN 14-16, 1993 CL ARLINGTON, VA SP WASHINGTON CHROMATOG DISCUSS GRP ID PURIFICATION AB The components in 3 g of the commercial color additive FD&C Red No. 3 were separated by pH-zone-refining counter-current chromatography. The main component, 2',4',5',7' -tetraiodofluorescein, and two positional isomeric lower-iodinated subsidiary colors, 2',4',5'-triiodofluorescein and 2',4',7'-triiodoffuorescein, were isolated and characterized by H-1 NMR and chemical ionization mass spectrometry. C1 US FDA,OFF SCI ANAL & SUPPORT,WASHINGTON,DC 20204. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. RP WEISZ, A (reprint author), US FDA,OFF COSMET & COLORS,WASHINGTON,DC 20204, USA. NR 18 TC 27 Z9 28 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JAN 14 PY 1994 VL 658 IS 2 BP 505 EP 510 DI 10.1016/0021-9673(94)80042-1 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA MW231 UT WOS:A1994MW23100031 ER PT J AU CASTRONOVO, V KUSAKA, M CHARIOT, A GIELEN, J SOBEL, M AF CASTRONOVO, V KUSAKA, M CHARIOT, A GIELEN, J SOBEL, M TI HOMEOBOX GENES - POTENTIAL CANDIDATES FOR THE TRANSCRIPTIONAL CONTROL OF THE TRANSFORMED AND INVASIVE PHENOTYPE SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID PRE-B; VERTEBRATE HOMEOBOX; MYELOID-LEUKEMIA; EXPRESSION; TRANSLOCATION; PROTEINS; HOMEODOMAIN; CANCER; CELLS; DIFFERENTIATION AB The transformation of a cell and the acquisition of the invasive and metastatic phenotype result from the activation of a group of complex cellular processes rather than from the effect of a single gene product. It is likely that the coordination of the multiple genes involved in malignancy is under the control of a few genes that act as master genes or orchestrator genes. The latter probably code for transcription factors that control the genetic program for tumor invasion and metastasis. Homeobox genes are a family of transcription factors that contain a 183 bp highly conserved nucleotide sequence coding for a 61 amino acid domain that binds specifically to DNA. First discovered in Drosphila as genes controlling segmentation and segment identity, homeobox genes have since been identified in many other species including nematodes, frog, mouse and human. There is strong support for the suggestion that homeobox genes play a key role in development and differentiation. In humans, there are 38 homeobox genes organized in four clusters that are localized on chromosomes 2, 7, 12 and 17. The specific functions of each of these genes are generally unknown. Alterations in expression of several homeobox genes have been reported in a variety of malignant lesions, suggesting that they could play a role in the development of cancer. Using reverse transcriptase reaction coupled with polymerase chain reaction and degenerate oligonucleotides corresponding to the 5' and 3' ends of the highly conserved homeodomain, we amplified 130 bp cDNA fragments from the human breast cancer cell line MCF7 that were subsequently cloned into pBluescript vector. Sequencing of the clones, resulted in the identification of the homeodomains of four different human homeobox genes: HOXB6, HOXA1, HOXA10 and HOXC6. Further studies should determine the specific role of these four homeobox genes in the development and progression of human breast cancer and potentially determine if they might be good targets for gene therapy. C1 NCI, PATHOL LAB, BETHESDA, MD 20892 USA. RP CASTRONOVO, V (reprint author), UNIV LIEGE, METASTASIS RES LAB, TOUR PATHOL, 3, BAT B-35, B-4000 LIEGE, BELGIUM. NR 40 TC 35 Z9 38 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JAN 13 PY 1994 VL 47 IS 1 BP 137 EP 143 DI 10.1016/0006-2952(94)90447-2 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MV680 UT WOS:A1994MV68000019 PM 7906121 ER PT J AU TOMASZEWSKI, KE MELNICK, RL AF TOMASZEWSKI, KE MELNICK, RL TI IN-VITRO EVIDENCE FOR INVOLVEMENT OF COA THIOESTERS IN PEROXISOME PROLIFERATION AND HYPOLIPIDAEMIA SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE PEROXISOME PROLIFERATOR; FATTY ACID METABOLISM; ACETYL-COA CARBOXYLASE; HEPATOCYTE; COA THIOESTER; (RAT) ID FATTY-ACID ANALOGS; COENZYME-A THIOESTERS; PROTEIN KINASE-C; RAT-LIVER; ACYL-COA; HYPOLIPEMIC DRUGS; STRUCTURAL REQUIREMENTS; OXIDASE ACTIVITY; INDUCTION; MITOCHONDRIA AB The mechanisms of peroxisomal induction and hypolipidaemia caused by treatment with peroxisome proliferators, such as nafenopin and clofibrate, remain to be elucidated. Proposed mechanisms include receptor-mediated processes or adaptations resulting from disruption of hepatic lipid metabolism. The latter mechanism was investigated in a series of in vitro studies. Incubation of primary rat hepatocytes with various carboxyl-containing compounds revealed no clear common factor which imparted potency as a peroxisomal inducer. Inhibitors of fatty acyl-CoA synthetase, norepinephrine and desulpho-CoA, however, decreased the level of peroxisomal induction by nafenopin in rat hepatocytes, suggesting that activation of carboxyl-containing compounds to their CoA thioesters may be a necessary step in initiating peroxisome proliferation. Coenzyme A thioesters of nafenopin, clofibric acid and other carboxyl-containing chemicals were synthesised and found to inhibit the activity of acetyl-CoA carboxylase to varying degrees. The CoA thioester of nafenopin was the most potent inhibitor among this group (K-i=11.45.10(-5) M), but weaker than palmitoyl-CoA (K-i=2.22 10(-6) M), the feedback inhibitor of acetyl-CoA carboxylase. Hypolipidaemia caused by treatment with peroxisome proliferators may, therefore, be related to inhibition of fatty-acid synthesis by the corresponding CoA thioester derivative. C1 NIEHS,RES TRIANGLE PK,NC 27709. NR 41 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD JAN 13 PY 1994 VL 1220 IS 2 BP 118 EP 124 DI 10.1016/0167-4889(94)90126-0 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MY077 UT WOS:A1994MY07700003 PM 7906145 ER PT J AU METZ, DC PRADHAN, TK MROZINSKI, JE JENSEN, RT TURNER, RJ PATTO, RJ GARDNER, JD AF METZ, DC PRADHAN, TK MROZINSKI, JE JENSEN, RT TURNER, RJ PATTO, RJ GARDNER, JD TI EFFECT OF INHIBITION OF MICROSOMAL CA2+-ATPASE ON CYTOPLASMIC CALCIUM AND ENZYME-SECRETION IN PANCREATIC ACINI SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE SECRETAGOGUE; AMYLASE SECRETION; SIGNAL TRANSDUCTION; 2ND MESSENGER; ATPASE, CA-2+ ID INTRACELLULAR CA2+ STORES; AMYLASE RELEASE; TUMOR PROMOTER; SIGNAL TRANSDUCTION; INOSITOL PHOSPHATES; CYCLOPIAZONIC ACID; CELLULAR CALCIUM; PLASMA-MEMBRANE; THAPSIGARGIN; CELLS AB We used thapsigargin (TG), 2,5-di-tert-butyl-l,4-benzohydroquinone (BHQ) and cyclopiazonic acid (CPA), e ach of which inhibits microsomal Ca2+-ATPase, to evaluate the effects of this inhibition on cytoplasmic free calcium ([Ca2+](i)) and secretagogue-stimulated enzyme secretion in rat pancreatic acini. Using single-cell microspectrofluorimetry of fura-2-loaded acini we found that all three agents caused a sustained increase in [Ca2+](i) by mobilizing calcium from inositol-(l,4,5)-trisphosphate-sensitive intracellular calcium stores and by promoting influx of extracellular calcium. Concentrations of all three agents that increased [Ca2+](i) potentiated the stimulation of enzyme secretion caused by secretagogues that activate adenylate cyclase but inhibited the stimulation of enzyme secretion caused by secretagogues that activate phospholipase C. With BHQ, potentiation of adenylate cyclase-mediated enzyme secretion occurred immediately whereas inhibition of phospholipase C-mediated enzyme secretion occurred only after several min of incubation. In addition, the effects of BHQ and CPA on both [Ca2+](i) and secretagogue-stimulated enzyme secretion were reversed completely by washing whereas the actions of TG could not be reversed by washing. Concentrations of BHQ in excess of those that caused maximal changes in [Ca2+](i) inhibited all modes of stimulated enzyme secretion by a mechanism that was apparently unrelated to changes in [Ca2+](i). Finally, in contrast to the findings with TG and BHQ, CPA inhibited bombesin-stimulated enzyme secretion over a range of concentrations that was at least 10-fold lower than the range of concentrations over which CPA potentiated VIP-stimulated enzyme secretion. C1 ST LOUIS UNIV,MED CTR,DEPT INTERNAL MED,ST LOUIS,MO 63104. NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892. NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. NR 46 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD JAN 13 PY 1994 VL 1220 IS 2 BP 199 EP 208 DI 10.1016/0167-4889(94)90136-8 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MY077 UT WOS:A1994MY07700013 PM 7508754 ER PT J AU GOUNNI, AS LAMKHIOUED, B OCHIAI, K TANAKA, Y DELAPORTE, E CAPRON, A KINET, JP CAPRON, M AF GOUNNI, AS LAMKHIOUED, B OCHIAI, K TANAKA, Y DELAPORTE, E CAPRON, A KINET, JP CAPRON, M TI HIGH-AFFINITY IGE RECEPTOR ON EOSINOPHILS IS INVOLVED IN DEFENSE AGAINST PARASITES SO NATURE LA English DT Article ID EPIDERMAL LANGERHANS CELLS; FC-EPSILON-RI; IMMUNOGLOBULIN-E; ALPHA-SUBUNIT; 2ND RECEPTOR; CHAIN; GENE; RESISTANCE; EXPRESSION; PRODUCTS AB PARASITIC infections are often associated with eosinophilia and high levels of immunoglobulin E (IgE). This observation has led to speculation that eosinophils and IgE may act together in the immune response against parasites. In support of this hypothesis, IgE and eosinophils participate in cytotoxic reactions directed against Schistosoma mansoni larvae in vitro1,2. Furthermore, epidemiological studies have shown an inverse correlation between levels of specific IgE and rates of infection with Schistosoma3-5. The low-affinity IgE receptor (FcepsilonRII/CD23) was first incriminated in eosinophil activation 6,7. The fact that the high-affinity IgE receptor (FcepsilonRI)8,9 is not only expressed on mast cells and basophils but also on Langerhans cells10,11 led us to investigate the presence of FcepsilonRI on eosinophils. Here we show that FcepsilonRI is expressed on eosinophils from hypereosinophilic patients, is involved in eosinophil degranulation, and participates in eosinophil-mediated cytotoxicity against S. mansoni. Our results indicate that FcepsilonRI may play a major part in immune defence against parasites. C1 INST PASTEUR,CTR IMMUNOL & BIOL PARASITAIRE,UNITE MIXTE,INSERM,U167,CNRS 624,F-59019 LILLE,FRANCE. NIAID,MOLEC ALLERGY & IMMUNOL SECT,BETHESDA,MD 20892. CTR HOSP REG UNIV LILLE,SERV DERMATOL A,F-59000 LILLE,FRANCE. NR 23 TC 392 Z9 399 U1 2 U2 9 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JAN 13 PY 1994 VL 367 IS 6459 BP 183 EP 186 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MQ780 UT WOS:A1994MQ78000064 PM 8114916 ER PT J AU DIBISCEGLIE, AM AF DIBISCEGLIE, AM TI INTERFERON THERAPY FOR CHRONIC VIRAL-HEPATITIS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CONTROLLED TRIAL; ALFA RP DIBISCEGLIE, AM (reprint author), NIDDKD,BETHESDA,MD 20892, USA. NR 10 TC 23 Z9 23 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 13 PY 1994 VL 330 IS 2 BP 137 EP 138 DI 10.1056/NEJM199401133300211 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA MQ670 UT WOS:A1994MQ67000011 PM 8259170 ER PT J AU WEISSINGER, EM HENDERSON, DW MISCHAK, H GOODNIGHT, J MUSHINSKI, JF AF WEISSINGER, EM HENDERSON, DW MISCHAK, H GOODNIGHT, J MUSHINSKI, JF TI INDUCTION OF PLASMACYTOMAS THAT SECRETE MONOCLONAL ANTIPEPTIDE ANTIBODIES BY RETROVIRAL TRANSFORMATION SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE PROTEIN KINASE C-ETA; MONOCLONAL ANTIBODY; ABL-MYC; RETROVIRUS ID PROTEIN-KINASE-C; V-ABL; MYC; SEQUENCES AB ABL-MYC, a retrovirus that coexpresses v-abl and c-myc, was used to infect six BALB/c mice that had been immunized twice with a KLH-conjugated peptide, that consisted of the 18 carboxyterminal amino acids of protein kinase C-eta (PKC-eta). All mice developed transplantable, monoclonal plasmacytomas, and five out of six plasmacytomas secreted antigen-specific antibodies, even after transplantation. All these antibodies recognized PKC-eta on Western blots of crude cell lysates and did not cross react with other isoforms of the PKC family. C1 NCI,GENET LAB,BETHESDA,MD 20892. RI Mischak, Harald/E-8685-2011 NR 15 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JAN 12 PY 1994 VL 168 IS 1 BP 123 EP 130 DI 10.1016/0022-1759(94)90216-X PG 8 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA MU049 UT WOS:A1994MU04900015 PM 8288888 ER PT J AU JOHNSON, PS WANG, JB WANG, WF UHL, GR AF JOHNSON, PS WANG, JB WANG, WF UHL, GR TI EXPRESSED MU-OPIATE RECEPTOR COUPLES TO ADENYLATE-CYCLASE AND PHOSPHATIDYL-INOSITOL TURNOVER SO NEUROREPORT LA English DT Article DE G-PROTEIN; MORPHINE; DRUG ABUSE; PAIN; ANALGESIA ID DELTA-OPIOID RECEPTOR; BINDING-SITES; ENKEPHALIN; BRADYKININ; MORPHINE; AGONISTS; CLONING AB THE recently cloned rat mu opiate receptor cDNA has been expressed in COS and Chinese hamster ovary (CHO) cells to examine the coupling of this receptor to G-protein linked second messenger systems and examine possible coupling to multiple second messenger systems. Morphine (1 mu M) reduced both forskolin-stimulated cAMP levels and IP3 levels by 20 +/- 5 and 34 +/- 8% respectively in COS and CHO cell cultures expressing the cloned rat mu receptor cDNA. Both effects could be blocked by naloxone and Gpp(NH)p. These results represent the first clear representation of the second messenger system promiscuity possible with a single cloned opiate receptor. C1 NATL INST DRUG ABUSE,ADDICT RES CTR,MOLEC NEUROBIOL BRANCH,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. NR 23 TC 49 Z9 51 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JAN 12 PY 1994 VL 5 IS 4 BP 507 EP 509 DI 10.1097/00001756-199401120-00035 PG 3 WC Neurosciences SC Neurosciences & Neurology GA MX730 UT WOS:A1994MX73000035 PM 8003685 ER PT J AU VUISTER, GW KIM, SJ WU, C BAX, A AF VUISTER, GW KIM, SJ WU, C BAX, A TI NMR EVIDENCE FOR SIMILARITIES BETWEEN THE DNA-BINDING REGIONS OF DROSOPHILA-MELANOGASTER HEAT-SHOCK FACTOR AND THE HELIX-TURN-HELIX AND HNF-3/FORKHEAD FAMILIES OF TRANSCRIPTION FACTORS SO BIOCHEMISTRY LA English DT Note ID CHEMICAL-SHIFTS; SECONDARY STRUCTURE; ACTIVATOR PROTEIN; SPECTRA; ALPHA; COMPLEX AB Heteronuclear multidimensional NMR experiments of residues 33-163 of the DNA-binding domain of Drosophila heat shock factor, dHSF(33-163), were recorded, using only 3 mg of uniformly N-15-labeled or 2 mg of uniformly N-15/C-13-labeled protein. The polypeptide consists of a structured part comprising three helices, a three-stranded antiparallel beta-sheet, with the first two strands connected by a four-residue type I tight turn. The second helix is disrupted at its C-terminal end by a proline residue and is followed by an extended turn, leading to the third helix. The dHSF(33-163) protein is unstructured at its N- and C-termini, and a third unstructured region is found from Thr113 to Arg124. Exchange broadening of the N-15-H-1 correlations upon titration of N-15 labeled HSF with a 13-base-pair DNA duplex suggests a DNA-binding motif in which the third helix acts as the recognition helix. Both the secondary structure and DNA-binding pattern of dHSF(33-163) suggest that the overall topology resembles that the helix-turn-helix bacterial activator CAP [Weber, 1. T., & Steitz, T. A. (1987) J. Mol. Biol. 198, 311-326] and the liver-specific transcription factor HNF-3gamma, the prototype of the HNF-3/forkhead protein family [Clark, K. L., Halay, E. D., Lai, E., & Burley, S. K. (1993) Nature 364, 412-420]. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 37 TC 63 Z9 63 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 11 PY 1994 VL 33 IS 1 BP 10 EP 16 DI 10.1021/bi00167a002 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MQ877 UT WOS:A1994MQ87700003 PM 8286326 ER PT J AU LI, H HALLOWS, WH PUNZI, JS MARQUEZ, VE CARRELL, HL PANKIEWICZ, KW WATANABE, KA GOLDSTEIN, BM AF LI, H HALLOWS, WH PUNZI, JS MARQUEZ, VE CARRELL, HL PANKIEWICZ, KW WATANABE, KA GOLDSTEIN, BM TI CRYSTALLOGRAPHIC STUDIES OF 2 ALCOHOL DEHYDROGENASE-BOUND ANALOGS OF THIAZOLE-4-CARBOXAMIDE ADENINE-DINUCLEOTIDE (TAD), THE ACTIVE ANABOLITE OF THE ANTITUMOR AGENT TIAZOFURIN SO BIOCHEMISTRY LA English DT Article ID INOSINE 5'-PHOSPHATE DEHYDROGENASE; MYELOID CELL MATURATION; IMP DEHYDROGENASE; LEUKEMIA-CELLS; INHIBITORY PROPERTIES; DIFFERENTIATION; BINDING; CRYSTAL; EXPRESSION; INDUCTION AB Thiazole-4-carboxamide adenine dinucleotide (TAD) is the active anabolite of the antitumor drug tiazofurin. Beta-methylene TAD (beta-TAD) is a phosphodiesterase-resistant analogue of TAD, active in tiazofurin-resistant cells. Beta-methylene SAD (beta-SAD) is the active selenium derivative of beta-TAD. Both agents are analogues of the cofactor NAD and are capable of acting as general dehydrogenase inhibitors. Crystal structures of beta-TAD and beta-SAD bound to horse liver alcohol dehydrogenase (LADH) are presented at 2.9 and 2.7 angstrom, respectively. Both complexes crystallize in the orthorhombic space group C222(1) and are isomorphous to apo-LADH. Complexes containing beta-TAD and beta-SAD were refined to crystallographic R values of 15% and 16%, respectively, for reflections between 8 angstrom and the minimum d spacing. Conformations of both inhibitors are similar. Beta-TAD and beta-SAD bind to the ''open'' form of LADH in the normal cofactor-binding cleft between the coenyzme and catalytic domains of each monomer. Binding at the adenosine end of each inhibitor resembles that of NAD. However, the positions of the thiazole and selenazole heterocycles are displaced away from the catalytic Zn cation by approximately 4 angstrom. Close intramolecular S-O and Se-O contacts observed in the parent nucleoside analogues are maintained in both LADH-bound beta-TAD and beta-SAD, respectively. These conformational constraints may influence the binding specificity of the inhibitors. C1 UNIV ROCHESTER,SCH MED & DENT,DEPT BIOPHYS,ROCHESTER,NY 14642. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. FOX CHASE CANC CTR,INST CANC RES,PHILADELPHIA,PA 19111. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. FU NCI NIH HHS [CA 10925, CA 45145] NR 62 TC 65 Z9 66 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 11 PY 1994 VL 33 IS 1 BP 23 EP 32 DI 10.1021/bi00167a004 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MQ877 UT WOS:A1994MQ87700005 PM 8286346 ER PT J AU ARCHER, SJ VINSON, VK POLLARD, TD TORCHIA, DA AF ARCHER, SJ VINSON, VK POLLARD, TD TORCHIA, DA TI ELUCIDATION OF THE POLY-L-PROLINE BINDING-SITE IN ACANTHAMOEBA PROFILIN-I BY NMR-SPECTROSCOPY SO FEBS LETTERS LA English DT Article DE BINDING SITE; PROTEIN-PROTEIN INTERACTION; NUCLEAR MAGNETIC RESONANCE; NUCLEAR MAGNETIC RESONANCE; 2-DIMENSIONAL; PROFILIN; POLYPROLINE; ACANTHAMOEBA ID HETERONUCLEAR NMR; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; SH3 DOMAIN; PROTEINS; IDENTIFICATION; PROFILACTIN; COMPLEX AB The multifunctional protein profilin is one of the most abundant proteins in the cytoplasm and is thought to regulate actin assembly and the phosphoinositide signaling pathway. Profilin binds to several different ligands including actin, poly-L-proline, and the head groups of polyphosphoinositides. Knowledge of profilin/ligand interactions is important for understanding the physiology of profilin in the cell. As a first step in the characterization of profilin/ligand complexes, we have studied a profilin/poly-L-proline complex in solution using high resolution NMR spectroscopy. Analysis of profilin NOE's and chemical shift data indicates that the protein secondary structure is conserved upon binding to poly-L-proline and that the binding site is located between the N- and C-terminal helices in a region rich in highly conserved aromatic sidechains. This site is adjacent to the proposed binding site for actin. In addition, the rate constant for dissociation of the complex is found to be 1.6 +/- 0.2 x 10(4) s(-1). C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT CELL BIOL & ANAT,BALTIMORE,MD 21205. FU NIGMS NIH HHS [GM-35171, GM13620] NR 38 TC 54 Z9 54 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JAN 10 PY 1994 VL 337 IS 2 BP 145 EP 151 DI 10.1016/0014-5793(94)80262-9 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA MR464 UT WOS:A1994MR46400006 PM 8287969 ER PT J AU TAYLOR, JA WATSON, MA DEVEREUX, TR MICHELS, RY SACCOMANNO, G ANDERSON, M AF TAYLOR, JA WATSON, MA DEVEREUX, TR MICHELS, RY SACCOMANNO, G ANDERSON, M TI P53 MUTATION HOTSPOT IN RADON-ASSOCIATED LUNG-CANCER SO LANCET LA English DT Note ID TUMOR SUPPRESSOR GENE; JAPAN AB Mutations in gene p53 are the most common defects in lung cancer and may be a pathway through which environmental carcinogens initiate cancer. We investigated p53 mutations in lung cancers from uranium miners with high radon exposure. 16 (31%) of 52 large-cell and squamous-cell cancers from miners contained the same AGG to ATG transversion at codon 249, including cancers from 3 or 5 miners who had never smoked. This specific mutation has been reported in only 1 of 241 published p53 mutations from lung cancers. The codon 249 mutation may be a marker for radon-induced lung cancer. C1 NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. ST MARYS HOSP,GRAND JCT,CO. RP TAYLOR, JA (reprint author), NIEHS,EPIDEMIOL BRANCH,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI taylor, jack/0000-0001-5303-6398 NR 10 TC 131 Z9 141 U1 1 U2 4 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JAN 8 PY 1994 VL 343 IS 8889 BP 86 EP 87 DI 10.1016/S0140-6736(94)90818-4 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA MQ092 UT WOS:A1994MQ09200013 PM 7903781 ER PT J AU PATCHEV, VK KARALIS, K CHROUSOS, GP AF PATCHEV, VK KARALIS, K CHROUSOS, GP TI EFFECTS OF EXCITATORY AMINO-ACID TRANSMITTERS ON HYPOTHALAMIC CORTICOTROPIN-RELEASING HORMONE (CRH) AND ARGININE-VASOPRESSIN (AVP) RELEASE IN-VITRO - IMPLICATIONS IN PITUITARY-ADRENAL REGULATION SO BRAIN RESEARCH LA English DT Article DE EXCITATORY AMINO ACID; CORTICOTROPIN-RELEASING HORMONE; VASOPRESSIN; HYPOTHALAMUS ID RAT; SECRETION; RECEPTORS; ADRENOCORTICOTROPIN; GLUTAMATE; ASPARTATE; ANTAGONISTS; PROLACTIN; AGONISTS; INVITRO AB The effect of excitatory amino acid (EAA) on the release of CRH and AVP - two major neurohumoral activators of the hypothalamic-pituitary-adrenal axis - was studied by in vitro perifusion of hypothalamic organ explants with various concentrations of EAA receptor agonists and antagonists. The agonists L-glutamate (GLU), kainic acid (KAIN) and L-aspartate (ASP) significantly decreased CRH release, while N-methyl-D-aspartate (NMDA) and quisqualic acid (QUIS) did not affect this parameter. AVP release was significantly stimulated by ASP and NMDA, decreased by KAIN and QUIS, and not influenced by GLU. Co-perifusion with equimolar concentrations of ASP and the selective NMDA receptor antagonist D-alpha-aminoadipic acid (aAA) partially diminished the effect of ASP on AVP release, but failed to affect ASP-induced suppression of CRH secretion. The broad-spectrum EAA receptor antagonist kynurenic acid (KYN) completely abolished ASP effects on CRH and AVP release in vitro. The results suggest that EAA transmitters might participate in the regulation of hypothalamic-pituitary-adrenal axis by differentially affecting the release of the two major ACTH secretagogues. In addition, EAA effects on hypothalamic CRH and AVP secretion appear to employ more than one subtype of amino acid receptors. C1 NICHHD, DEB, PEDIAT ENDOCRINOL SECT, BETHESDA, MD 20892 USA. NR 27 TC 31 Z9 32 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 7 PY 1994 VL 633 IS 1-2 BP 312 EP 316 DI 10.1016/0006-8993(94)91554-7 PG 5 WC Neurosciences SC Neurosciences & Neurology GA MQ949 UT WOS:A1994MQ94900040 PM 7907936 ER PT J AU DIXON, KH LANPHER, BC CHIU, J KELLEY, K COWAN, KH AF DIXON, KH LANPHER, BC CHIU, J KELLEY, K COWAN, KH TI A NOVEL CDNA RESTORES REDUCED FOLATE CARRIER ACTIVITY AND METHOTREXATE SENSITIVITY TO TRANSPORT DEFICIENT CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID BINDING PROTEINS; TUMOR-CELLS; RECEPTOR; RESISTANCE; TOXICITY AB Mammalian cells accumulate reduced folates and methotrexate, a folate antagonist, through the reduced-folate carrier (RFC) (Goldman, I. D., Lichtenstein, N. S., and Oliverio, V. T. (1968) J. Biol. Chem. 243, 5007-5017). This study describes the isolation and expression of a cDNA clone that restores RFC activity to human breast cancer cells defective in this transporter. The cDNA codes for a peptide (mRFC1) of 58 kDa, whose hydropathy plot, resembling those of mammalian sugar transporters, predicts that it may be a member of a superfamily of transporter genes. Transfection of methotrexate-resistant (MTX(R)) ZR-75-1 cells with an expression vector, pRFC1, that codes for this peptide restores their ability to accumulate methotrexate. Furthermore, transport of methotrexate into pRFC1-transfected cells is blocked by a 10-fold molar excess of the reduced folate, 5-formyltetrahydrofolic acid, but is unaffected by folic acid. The increase in methotrexate uptake that is observed in pRFC1-transfected MTX(R) ZR-75-1 cells reverses their resistance to this antitumor agent. RP NCI, MED BRANCH, MED BREAST CANC SECT, BETHESDA, MD 20892 USA. NR 35 TC 200 Z9 203 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 7 PY 1994 VL 269 IS 1 BP 17 EP 20 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR219 UT WOS:A1994MR21900005 PM 8276792 ER PT J AU MAUVIEL, A LAPIERE, JC HALCIN, C EVANS, CH UITTO, J AF MAUVIEL, A LAPIERE, JC HALCIN, C EVANS, CH UITTO, J TI DIFFERENTIAL CYTOKINE REGULATION OF TYPE-I AND TYPE-VII COLLAGEN GENE-EXPRESSION IN CULTURED HUMAN DERMAL FIBROBLASTS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR-BETA; NECROSIS-FACTOR-ALPHA; MESSENGER-RNA LEVELS; HUMAN SYNOVIAL-CELLS; EPIDERMOLYSIS-BULLOSA; TRANSCRIPTIONAL ACTIVATION; EPIDERMAL-KERATINOCYTES; STIMULATES COLLAGENASE; LEUKOREGULIN; SKIN AB Type VII collagen is the major component of anchoring fibrils in the cutaneous basement membrane zone. In this study, we have examined the effects of various cytokines on the expression of types I and VII collagen genes in dermal fibroblasts in culture. The pro-inflammatory cytokines, interleukin-1alpha (IL-1alpha), interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and leukoregulin (LR) strongly elevated (approximately 5-9-fold) type VII collagen mRNA levels, as measured by Northern blot hybridizations. These effects were also observed at the protein level by indirect immunofluorescence using a monoclonal antibody specific for type VII collagen. By contrast, IL-1beta had only a slight stimulatory effect (approximately 2-fold) on type I collagen gene expression, while TNF-alpha and LR markedly reduced type I collagen mRNA steady-state levels. Interestingly, IL-1, TNF-alpha and LR had additive effects with transforming growth factor-beta (TGF-beta) on type VII collagen gene expression, whereas they counteracted the up-regulatory effect of TGF-beta on type I collagen gene expression. Thus, our data indicate that the modulation of type I and type VII collagen gene expression by cytokines involves different regulatory pathways. C1 THOMAS JEFFERSON UNIV, JEFFERSON MED COLL,DEPT DERMATOL,233 S 10TH ST, RM 450, PHILADELPHIA, PA 19107 USA. THOMAS JEFFERSON UNIV, JEFFERSON MED COLL, DEPT BIOCHEM & MOLEC BIOL, PHILADELPHIA, PA 19107 USA. NCI, TUMOR BIOL SECT, BIOL LAB, BETHESDA, MD 20892 USA. RI MAUVIEL, Alain/F-6251-2013 FU NIAMS NIH HHS [T32-AR07561, P01-AR38923] NR 36 TC 42 Z9 42 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 7 PY 1994 VL 269 IS 1 BP 25 EP 28 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR219 UT WOS:A1994MR21900007 PM 8276802 ER PT J AU HART, MJ EVA, A ZANGRILLI, D AARONSON, SA EVANS, T CERIONE, RA ZHENG, Y AF HART, MJ EVA, A ZANGRILLI, D AARONSON, SA EVANS, T CERIONE, RA ZHENG, Y TI CELLULAR-TRANSFORMATION AND GUANINE-NUCLEOTIDE EXCHANGE ACTIVITY ARE CATALYZED BY A COMMON DOMAIN ON THE DBL ONCOGENE PRODUCT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID GTP-BINDING PROTEIN; MOLECULAR-CLONING; ACTIVATING PROTEIN; ESCHERICHIA-COLI; CDC42HS PROTEIN; RAS; YEAST; GENE; IDENTIFICATION; POLARITY AB The dbl oncogene product contains a 238-amino acid domain, which is shared by an expanding family of growth regulatory proteins. These include the Saccharomyces cerevisiae cell division cycle protein, CDC24, the breakpoint cluster region protein, the ect2 and vav oncogene products, and the brain GDP-releasing factor for Ras. Previous studies have provided evidence that oncogenic Dbl or an associated protein stimulates GDP dissociation from the human species (Hs) homolog of CDC42. We show here that Dbl specifically complexes with the GDP-bound forms of CDC42Hs and RhoA, but not Rac1 or TC10, and that this specificity correlates with the ability of Dbl to act as a GDP-releasing factor. Small deletions throughout the Dbl domain, which inactivate transformation, eliminated the ability of Dbl to stimulate GDP dissociation, whereas deletions outside of this domain did not impair either function. Finally, the Dbl domain itself, when expressed and purified as a recombinant protein, was shown to stimulate GDP dissociation from purified, recombinant CDC42Hs. These findings establish that a minimal unit on Dbl that is critical to its transforming function directly regulates GDP-GTP exchange activity. C1 CORNELL UNIV,DEPT PHARMACOL,ITHACA,NY 14853. CORNELL UNIV,DEPT BIOCHEM & CELL & MOLEC BIOL,ITHACA,NY 14853. NCI,BETHESDA,MD 20892. ONYX PHARMACEUT,RICHMOND,CA 94806. RI Zheng, Yi/J-7235-2015; Eva, Alessandra/J-8268-2016 OI Zheng, Yi/0000-0001-7089-6074; Eva, Alessandra/0000-0003-2949-078X FU NIGMS NIH HHS [GM47458] NR 28 TC 269 Z9 271 U1 1 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 7 PY 1994 VL 269 IS 1 BP 62 EP 65 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR219 UT WOS:A1994MR21900017 PM 8276860 ER PT J AU HYUN, SW PARK, K LEE, YS LEE, YI KIM, SJ AF HYUN, SW PARK, K LEE, YS LEE, YI KIM, SJ TI INHIBITION OF PROTEIN PHOSPHATASES ACTIVATES P4 PROMOTER OF THE HUMAN INSULIN-LIKE GROWTH FACTOR-II GENE THROUGH THE SPECIFIC PROMOTER ELEMENT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR SUPPRESSOR WT1; HEPATITIS-B VIRUS; OKADAIC ACID; TRANSCRIPTION FACTOR; 3T3 CELLS; C-FOS; EXPRESSION; PHOSPHORYLATION; REPRESSION; SEQUENCES AB To understand the transcriptional regulation of the human insulin-like growth factor II (IGF-II) gene, we examined the effects of okadaic acid, a potent in vitro inhibitor of protein phosphatases, on the activation of human IGF-II gene expression. Treatment of A-549 human lung adenocarcinoma cells with okadaic acid increased expression of the IGF-II mRNAs. Since the 4.8-kb mRNA is transcribed under the control of human IGF-II P4 promoter, we examined the P4 promoter element responsible for the okadaic acid-mediated transcriptional activation. Transfection of IGF-II P4 promoter-chloramphenicol acetyltransferase constructs demonstrated that the effects of okadaic acid on the induction of IGF-II gene expression are mediated through multiple promoter elements, including an Egr-1 consensus element. We have also shown that okadaic acid induced the expression of the transcription factor Egr-1. Moreover, by using a GAL4-Egr-1 fusion protein, we have directly demonstrated that okadaic acid positively regulates Egr-1 transcriptional activity in vivo. These results indicate that protein phosphatases play an-important role in the transcriptional regulation of the IGF-II. C1 KOREA INST SCI & TECHNOL,GENET ENGN RES INST,MOLEC GENET LAB,TAEJON 305606,SOUTH KOREA. NCI,CHEMOPREVENT,BETHESDA,MD 20892. CATHOLIC MED UNIV,SEOUL 137040,SOUTH KOREA. NR 35 TC 14 Z9 14 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 7 PY 1994 VL 269 IS 1 BP 364 EP 368 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR219 UT WOS:A1994MR21900061 PM 8276819 ER PT J AU BLUML, K MUTSCHLER, E WESS, J AF BLUML, K MUTSCHLER, E WESS, J TI IDENTIFICATION OF AN INTRACELLULAR TYROSINE RESIDUE CRITICAL FOR MUSCARINIC RECEPTOR-MEDIATED STIMULATION OF PHOSPHATIDYLINOSITOL HYDROLYSIS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-ADRENERGIC-RECEPTOR; 3RD CYTOPLASMIC LOOP; ACETYLCHOLINE-RECEPTOR; LIGAND-BINDING; DOMAINS; GS; SELECTIVITY; ACTIVATION; SUBTYPES; DELINEATION AB Several lines of evidence suggest that the N-terminal portion of the third cytoplasmic loop (i3) of muscarinic and other G protein-coupled receptors is of pivotal importance for G protein recognition and activation. The present study was designed to identify specific amino acids within this domain required for muscarinic receptor-induced activation of G proteins mediating stimulation of phosphatidylinositol (PI) hydrolysis. Among the five mammalian muscarinic receptors (m1-m5), only the m1, m3, and m5 receptors are efficiently coupled to this second messenger pathway. Initially, we created a series of rat m3 receptor mutants in which short segments in the N terminus of the i3 loop were replaced with the corresponding m2 receptor sequences. The effect of these substitutions on m3 receptor-mediated stimulation of PI hydrolysis was studied in transiently transfected COS-7 cells. We found that a stretch of 4 amino acids (Arg252-Ile253-Tyr254-Lys255) located at the beginning of the i3 domain of the m3 muscarinic receptor is critically involved in receptor-mediated stimulation of PI hydrolysis. Further mutational analysis of this 4-amino acid segment by single amino acid substitutions demonstrated that only Tyr254 is essential for efficient activation of the PI pathway. This tyrosine residue is conserved among all PI-coupled muscarinic receptors as well as in many other biogenic amine and glycoprotein hormone receptors, suggesting that it may also play an important functional role in other G protein-coupled receptors. C1 NIDDKD,BIOORGAN CHEM LAB,BLDG 8A,RM B1A-09,BETHESDA,MD 20892. UNIV FRANKFURT,W-6000 FRANKFURT,GERMANY. NR 27 TC 52 Z9 53 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 7 PY 1994 VL 269 IS 1 BP 402 EP 405 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR219 UT WOS:A1994MR21900068 PM 8276826 ER PT J AU SPACCIAPOLI, P NOSSAL, NG AF SPACCIAPOLI, P NOSSAL, NG TI A SINGLE MUTATION IN BACTERIOPHAGE-T4 DNA-POLYMERASE (A737V, TSL141) DECREASES ITS PROCESSIVITY AS A POLYMERASE AND INCREASES ITS PROCESSIVITY AS A 3' -] 5' EXONUCLEASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEOXYRIBONUCLEIC-ACID POLYMERASE; ESCHERICHIA-COLI; ACCESSORY PROTEINS; CB120 ANTIMUTATOR; BIOCHEMICAL BASIS; KLENOW FRAGMENT; REPLICATION; SITE; GENE; PURIFICATION AB The bacteriophage T4 DNA polymerase mutant A737V (tsL141 and tsCB120) was originally characterized as temperature-sensitive for DNA replication and an antimutator for transition mutations. Its antimutator phenotype is suppressed by the L771F mutation (Reha-Krantz, L. J., Stocki, S., Nonay, R., and Maughan, C. (1989) J. Cell. Biochem. 13D, 140). We find that the A737V polymerase arrests much more frequently than the wild type when polymerizing on primed single-stranded DNA templates. Although the 3' --> 5' exonuclease of the mutant is indistinguishable from the wild type on single-stranded DNA, it is more active than the wild type on duplex DNA. In a single encounter with the primer, the wild type polymerase can incorporate more than 50 nucleotides. The processivity of the A737V polymerase is less than the wild type as a polymerase, but is greater than the wild type as an exonuclease. The L771F polymerase resembles the wild type in each of these properties, while the double mutant (A737V, L771F) is intermediate between the two single mutants. Kinetic studies of wild type T4 DNA polymerase (Capson, T. L., Peliska, J. A., Kaboord, B. F., Frey, M. W., Lively, C., Dahlberg, M., and Benkovic, S. J. (1992) Biochemistry 31, 10984-10994) suggest that DNA binds first to the polymerase active site, before adopting a configuration in which it can be hydrolyzed by the exonuclease. Within this framework, our studies suggest that DNA moves more readily from the polymerase- to the exonuclease-competent configuration on the A737V mutant polymerase, and that this movement is decreased by the compensating L771F mutation. C1 NIDDKD,MOLEC & CELLULAR BIOL LAB,ROOM 2A-19,BETHESDA,MD 20892. NIDDKD,BIOCHEM PHARMACOL LAB,BETHESDA,MD 20892. NR 60 TC 48 Z9 48 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 7 PY 1994 VL 269 IS 1 BP 438 EP 446 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR219 UT WOS:A1994MR21900074 PM 8276833 ER PT J AU SPACCIAPOLI, P NOSSAL, NG AF SPACCIAPOLI, P NOSSAL, NG TI INTERACTION OF DNA-POLYMERASE AND DNA HELICASE WITHIN THE BACTERIOPHAGE-T4 DNA-REPLICATION COMPLEX - LEADING-STRAND SYNTHESIS BY THE T4 DNA-POLYMERASE MUTANT A737V (TSL141) REQUIRES THE T4 GENE-59 HELICASE ASSEMBLY PROTEIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACCESSORY PROTEINS; RNA PRIMERS; TEMPLATE; INVITRO; ANTIMUTATOR; MECHANISMS; HOLOENZYME; MUTATOR; FORK AB The bacteriophage T4 tsL141 (A737V) mutant in T4 DNA polymerase is temperature-sensitive for DNA replication and an antimutator for some types of mutations. In the accompanying paper (Spacciapoli, P., and Nossal, N. G. (1993) J. Biol. Chem. 269,438-446), we show that the purified A737V T4 DNA polymerase is less processive than the wild type enzyme as a polymerase, but is more processive as an exonuclease. The bacteriophage T4 multienzyme replication complex reconstituted with the A737V mutant polymerase is defective in both lagging and leading strand synthesis. On lagging strand templates, the A737V polymerase is stimulated by the gene 44/62 and 45 polymerase accessory proteins and the gene 32 DNA binding protein, but is still arrested at pause sites much more frequently than the wild type. In contrast to wild type T4 DNA polymerase, the A737V polymerase does not catalyze leading strand synthesis on a forked duplex template with the polymerase accessory proteins, 32 protein, and the gene 41 protein helicase. The A737V polymerase requires the T4 gene 59 helicase assembly protein, as well as the other proteins, to carry out this reaction. Each of these defects is suppressed by the intragenic L771F mutation that suppresses the antimutator phenotype of the A737V polymerase in vivo (Reha-Krantz, L. J., Stocki, S., Nonay, R., and Maughan, C. (1989) J. Cell. Biochem. 13D, 140). C1 NIDDKD,MOLEC & CELLULAR BIOL,BLDG 8,ROOM 2A-19,BETHESDA,MD 20892. NIDDKD,BIOCHEM PHARMACOL LAB,BETHESDA,MD 20892. NR 29 TC 48 Z9 48 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 7 PY 1994 VL 269 IS 1 BP 447 EP 455 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR219 UT WOS:A1994MR21900075 PM 8276834 ER PT J AU OPOKU, J SIMONS, SS AF OPOKU, J SIMONS, SS TI ABSENCE OF INTRAMOLECULAR DISULFIDES IN THE STRUCTURE AND FUNCTION OF NATIVE RAT GLUCOCORTICOID RECEPTORS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING ACTIVITY; SITE-DIRECTED MUTAGENESIS; STEROID-BINDING; DEXAMETHASONE 21-MESYLATE; BOND FORMATION; SULFHYDRYL-GROUPS; REDOX REGULATION; PROTEIN; CYSTEINES; DOMAIN AB The presence of intramolecular disulfides in different functional states of the native glucocorticoid receptor in the absence of added oxidants has been examined on nonreducing SDS-polyacrylamide gels. Possible disulfides were trapped by the reaction of thiols in crude receptor solutions with methyl methanethiolsulfonate or iodoacetamide. The presence of diffuse bands at lower molecular weights than either the fully reduced or the thiol-blocked species for both the intact 98-kDa receptor and the 42-kDa chymotryptic fragment was diagnostic of an intramolecular disulfide(s) that had undergone thiol-disulfide rearrangements. However, both the rearrangements and the formation of intramolecular disulfides were found to occur only with denatured receptors during gel analysis. It appears that the thiols normally complexed with zinc in the zinc fingers may be recruited for disulfide bond formation. Finally, even when a documented intramolecular disulfide was formed in solutions of the native protein, thiol-disulfide rearrangements did not occur. The tertiary structure of the receptor is thus constituted in a manner that not only limits the formation of disulfides but also prevents the usually facile rearrangements of disulfide bond-containing structures to receptor forms that may have greatly reduced activity. Therefore, although intramolecular disulfide bonds may be of transitory importance, the structural or functional changes of native glucocorticoid receptors that are associated with steroid binding, activation, and dissociation of heat shock protein 90 neither involve nor require the formation or reduction of stable intramolecular disulfides. C1 NIDDK,LMCB,STEROID HORMONES SECT,BLDG 8,RM B2A-07,BETHESDA,MD 20892. NR 50 TC 13 Z9 13 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 7 PY 1994 VL 269 IS 1 BP 503 EP 510 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR219 UT WOS:A1994MR21900082 PM 8276843 ER PT J AU CHOI, OH ADELSTEIN, RS BEAVEN, MA AF CHOI, OH ADELSTEIN, RS BEAVEN, MA TI SECRETION FROM RAT BASOPHILIC RBL-2H3 CELLS IS ASSOCIATED WITH DIPHOSPHORYLATION OF MYOSIN LIGHT-CHAINS BY MYOSIN LIGHT-CHAIN KINASE AS WELL AS PHOSPHORYLATION BY PROTEIN-KINASE-C SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LEUKEMIA-CELLS; TYROSINE PHOSPHORYLATION; IGE RECEPTOR; HISTAMINE-RELEASE; MAST-CELLS; SIGNAL TRANSDUCTION; PLATELET MYOSIN; PHOSPHOLIPASE C-GAMMA-1; ANTIGEN STIMULATION; SYNERGISTIC SIGNALS AB The phosphorylation of myosin light chains and heavy chains by protein kinase C is known to be temporally correlated with Ca2+-dependent secretion of granules from RBL-2H3 cells (Ludowyke, R. I., Peleg, I., Beaven, M. A., and Adelstein, IL S. (1989) J. Biol. Chem. 264, 12492-12501). We now report that whereas myosin light chains are predominantly monophosphorylated by the Ca2+/calmodulin-dependent myosin light chain kinase at serine 19 in unstimulated cells, stimulation of RBL-2H3 cells with antigen or other stimulants causes additional phosphorylation of myosin light chains by myosin light chain kinase at threonine 18, as well as by protein kinase C at serine 1 or serine 2. This diphosphorylation at serine 19 and threonine 18 by myosin light chain kinase and the monophosphorylation by protein kinase C is correlated with the rate and extent of degranulation. Secretion occurs whenever phosphorylation by both enzymes is stimulated by antigen or by the combination of low concentrations of A23187 (50 nM) and phorbol 12-myristate 13-acetate (20 nM). These phosphorylations appear to be closely associated with exocytosis in RBL-2H3 cells. Thus, phosphorylation, as well as secretion, can be blocked by the kinase inhibitors KT5926 and ML-7. More specifically, phorbol ester alone induces phosphorylation of myosin light chains by protein kinase C exclusively, but fails to induce secretion until accompanied by low concentrations of A23187, which activates myosin light chain kinase. Conversely, selective suppression of phosphorylation by protein kinase C (with Ro31-7549 in antigen-stimulated cells) suppresses degranulation, thereby indicating a requirement for protein kinase C. C1 NHLBI,MOLEC CARDIOL LAB,BETHESDA,MD 20892. RP CHOI, OH (reprint author), NHLBI,CHEM PHARMACOL LAB,BLDG 10,RM 8N108,BETHESDA,MD 20892, USA. OI Adelstein, Robert/0000-0002-8683-2144 NR 49 TC 83 Z9 83 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 7 PY 1994 VL 269 IS 1 BP 536 EP 541 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR219 UT WOS:A1994MR21900086 PM 8276847 ER PT J AU KOHN, KW ORR, A OCONNOR, PM GUZIEC, LJ GUZIEC, FS AF KOHN, KW ORR, A OCONNOR, PM GUZIEC, LJ GUZIEC, FS TI SYNTHESIS AND DNA-SEQUENCE SELECTIVITY OF A SERIES OF MONOFUNCTIONAL AND DIFUNCTIONAL 9-AMINOACRIDINE NITROGEN MUSTARDS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ALKYLATION; ANTITUMOR AB The aim of this work was to identify nitrogen mustards that would react selectively with DNA, particularly in G-rich regions. A sei ies of mono- and difunctional nitrogen mustards was synthesized in which the (2-chloroethyl)amino functions were connected to the N-9 of 9-aminoacridine by way of a spacer chain consisting of two to six methylene units. The length of the spacer chain connecting the alkylating and putative DNA-intercalating groups was found to affect the preference for the alkylation of different guanine-N-7 positions in a DNA sequence. All of the compounds reacted preferentially at G's that are followed by G as do most other types of nitrogen mustards, but the degree of selectivity was greater. The compounds reacted at much lower concentrations than were required for comparable reaction by mechlorethamine (HN2), consistent with initial noncovalent binding to DNA prior to guanine-N-7 alkylation. The degree of DNA-sequence selectivity increased as the spacer-chain length decreased below four methylene units. Most strikingly, long spacer compounds reacted strongly at 5'-GT-3' sequences, Whereas this reaction was almost completely suppressed when-the spacer length was reduced to two or three methylenes. Mono- and difunctional compounds of a given spacer length showed no consistent difference in DNA-sequence preference. C1 NEW MEXICO STATE UNIV,DEPT CHEM & BIOCHEM,LAS CRUCES,NM 88003. RP KOHN, KW (reprint author), NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892, USA. NR 17 TC 26 Z9 26 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JAN 7 PY 1994 VL 37 IS 1 BP 67 EP 72 DI 10.1021/jm00027a008 PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA MQ715 UT WOS:A1994MQ71500008 PM 8289202 ER PT J AU TSARFATY, I RONG, S RESAU, JH SHEN, RL DASILVA, PP VANDEWOUDE, GF AF TSARFATY, I RONG, S RESAU, JH SHEN, RL DASILVA, PP VANDEWOUDE, GF TI THE MET PROTOONCOGENE MESENCHYMAL TO EPITHELIAL-CELL CONVERSION SO SCIENCE LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; SCATTER FACTOR; LIVER-REGENERATION; FACTOR HGF; C-MET; PROTOONCOGENE; VIMENTIN; CYTOKERATINS; EXPRESSION; RECEPTOR AB Coexpression of the human Met receptor and its ligand, hepatocyte growth factor/scatter factor (HGF/SF), in NIH 3T3 fibroblasts causes the cells to become tumorigenic in nude mice. The resultant tumors display lumen-like morphology, contain carcinoma-like focal areas with intercellular junctions resembling desmosomes, and coexpress epithelial (cytokeratin) and mesenchymal (vimentin) cytoskeletal markers. The tumor cells also display enhanced expression of desmosomal and tight-junction proteins. The apparent mesenchymal to epithelial conversion of the tumor cells mimics the conversion that occurs during embryonic kidney development, suggesting that Met-HGF/SF signaling plays a role in this process as well as in tumors that express both epithelial and mesenchymal markers. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,POB B,FREDERICK,MD 21702. NCI,DIV CANC BIOL DIAG & CTR,INTRAMURAL RES PROGRAM,MATH BIOL LAB,MEMBRANE BIOL SECT,FREDERICK,MD 21702. RI Shen, Rulong/E-4079-2011 FU NCI NIH HHS [N01-CO-74101] NR 29 TC 185 Z9 188 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JAN 7 PY 1994 VL 263 IS 5143 BP 98 EP 101 DI 10.1126/science.7505952 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MQ301 UT WOS:A1994MQ30100040 PM 7505952 ER PT J AU RAY, PE MCCUNE, BK GOMEZ, RA RULEY, EJ KLOTMAN, PE AF RAY, PE MCCUNE, BK GOMEZ, RA RULEY, EJ KLOTMAN, PE TI EXPRESSION OF TRANSFORMING GROWTH FACTOR-BETA-3 IN HYPERTROPHIC JUXTAGLOMERULAR APPARATUS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. UNIV VIRGINIA,SCH MED,CHARLOTTESVILLE,VA 22908. CHILDRENS NATL MED CTR,WASHINGTON,DC 20010. RP RAY, PE (reprint author), NIDR,BETHESDA,MD 20892, USA. NR 5 TC 11 Z9 11 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 6 PY 1994 VL 330 IS 1 BP 68 EP 69 DI 10.1056/NEJM199401063300117 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA MP649 UT WOS:A1994MP64900029 PM 8259157 ER PT J AU LOE, H AF LOE, H TI BROAD PAYOFFS FROM ORAL-TISSUE RESEARCH SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP LOE, H (reprint author), NIDR,BETHESDA,MD 20892, USA. NR 2 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 JAN 5 PY 1994 VL 271 IS 1 BP 14 EP 14 DI 10.1001/jama.271.1.14 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA MN725 UT WOS:A1994MN72500005 PM 8258872 ER PT J AU YANOVSKI, SZ HOOFNAGLE, JH AF YANOVSKI, SZ HOOFNAGLE, JH TI VERY-LOW-CALORIE DIETS FOR OBESITY - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP YANOVSKI, SZ (reprint author), NIH,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 5 PY 1994 VL 271 IS 1 BP 25 EP 25 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA MN725 UT WOS:A1994MN72500015 ER PT J AU CLERICI, M LEVIN, JM KESSLER, HA HARRIS, A BERZOFSKY, JA LANDAY, AL SHEARER, GM AF CLERICI, M LEVIN, JM KESSLER, HA HARRIS, A BERZOFSKY, JA LANDAY, AL SHEARER, GM TI HIV-SPECIFIC T-HELPER ACTIVITY IN SERONEGATIVE HEALTH-CARE WORKERS EXPOSED TO CONTAMINATED BLOOD SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; CELL-MEDIATED-IMMUNITY; LYMPHOCYTES-T; SEROPOSITIVE INDIVIDUALS; INFECTED INDIVIDUALS; TYPE-1; SURVEILLANCE; RECOGNITION; RESPONSES AB Objective.-To evaluate human immunodeficiency virus (HIV) type 1-specific cellular immune responses in HIV-seronegative health care workers with occupational high-risk exposures to HIV-infected (HIV-positive) patients. Design.-Peripheral blood mononuclear cells (PBMCs) were obtained after occupational exposures to HIV, and PBMCs from health care workers exposed to HIV-negative patients served as controls. The PBMCs were stimulated in vitro with HIV envelope synthetic peptides. Interleukin 2 (IL-2) production was measured in a bioassay. The HIV antibody status was determined by standard enzyme-linked immunosorbent assays. Exposed individuals were also evaluated for HIV proviral DNA by polymerase chain reaction techniques. Participants.-The PBMCs from eight health care workers with high-risk exposures and nine control health care workers were studied. Results.-The PBMCs from all individuals showed strong IL-2 production to control antigens, indicating intact T-helper function. Interleukin 2 production to HIV peptides was detected in PBMCs from six of eight HIV-exposed individuals, but in only one of the nine health care workers exposed to HIV-negative body fluids (P<.008). None of the HIV-exposed health care workers became infected as determined by negative HIV antibody and polymerase chain reaction analysis after follow-up evaluation that ranged from 8 to 64 weeks. Conclusion.-Human immunodeficiency virus-specific T-helper activity was detected in six (75%) of eight HIV-negative health care workers with exposure to HIV-positive body fluids. Potent HIV-specific T-helper activity was detectable 4 to 8 weeks after the exposure and was lost in individuals followed up for 8 to 64 weeks. Three health care workers remained responsive at 8, 19, and 24 weeks. Exposure to HIV without evidence of subsequent infection appears to result in activation of cellular immunity without activation of antibody production. C1 NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B17,BETHESDA,MD 20892. NCI,METAB BRANCH,BETHESDA,MD 20892. RUSH PRESBYTERIAN ST LUKES MED CTR,DEPT IMMUNOL MICROBIOL,CHICAGO,IL 60612. RUSH PRESBYTERIAN ST LUKES MED CTR,DEPT MED,CHICAGO,IL 60612. NR 34 TC 177 Z9 178 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 5 PY 1994 VL 271 IS 1 BP 42 EP 46 DI 10.1001/jama.271.1.42 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA MN725 UT WOS:A1994MN72500029 PM 8258885 ER PT J AU KOHN, EC SAROSY, G BICHER, A LINK, C CHRISTIAN, M STEINBERG, SM ROTHENBERG, M ADAMO, DO DAVIS, P OGNIBENE, FP CUNNION, RE REED, E AF KOHN, EC SAROSY, G BICHER, A LINK, C CHRISTIAN, M STEINBERG, SM ROTHENBERG, M ADAMO, DO DAVIS, P OGNIBENE, FP CUNNION, RE REED, E TI DOSE-INTENSE TAXOL - HIGH RESPONSE RATE IN PATIENTS WITH PLATINUM-RESISTANT RECURRENT OVARIAN-CANCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PHASE-II TRIAL; COLONY-STIMULATING FACTOR; EVERY 21 DAYS; METASTATIC MELANOMA; CELL CARCINOMA; INFUSION; THERAPY; AGENT AB Background: Paclitaxel (Taxol), a diterpene plant product that promotes tubulin polymerization, has documented activity against a number. of solid tumors, including ovarian cancer and breast cancer. Purpose: Our purpose was to conduct a phase II clinical trial investigating the response of patients with advanced recurrent ovarian carcinoma to high-dose paclitaxel combined with granulocyte colony-stimulating factor (G-CSF). Methods: A prospective phase II clinical trial of patients with advanced-stage, recurrent ovarian cancer was undertaken. Patients received 250 mg/m2 paclitaxel every 21 days; cycles were given on a rigid schedule; delays were permitted only for extreme circumstances. G-CSF at a dose of 10 mug/kg per day was given to ameliorate myelosuppression. If a patient showed fever and neutropenia, G-CSF dosage was increased to 20 mug/kg per day so that paclitaxel dose intensity could be maintained. Patients were assessed for response every two cycles, and those with complete radiographic resolution of disease underwent peritoneoscopy. Results: Forty-four patients were assessable for response. Twenty-one had a reduction in tumor volume greater than 50%, yielding an objective response rate of 48% (21 of 44 patients, 95% confidence interval, 32%-63%). Six (14%) of the 44 patients had complete radiographic resolution of disease; two of the six also had negative biopsy specimens and washings at peritoneoscopy. Age, number of prior regimens, and clinical platinum resistance did not influence response rate or ability to maintain dose intensity. Dose intensity was maintained at the targeted level for up to 14 consecutive cycles of therapy. Conclusions: We observed a 48% response rate with dose-intense paclitaxel for patients with advanced-stage, platinum-resistant, recurrent ovarian cancer. The response rate is higher than previously reported for paclitaxel at a lower-dose in similar cohorts of patients treated without G-CSF. Comparison of phase II studies of paclitaxel suggests a dose-response relationship. Therapy with dose-intense paclitaxel and G-CSF should be considered for patients with advanced, platinum-refractory ovarian cancer. C1 NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,MED BRANCH,BLDG 10,ROOM 6N109,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BETHESDA,MD 20892. NR 30 TC 177 Z9 177 U1 1 U2 5 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 5 PY 1994 VL 86 IS 1 BP 18 EP 24 DI 10.1093/jnci/86.1.18 PG 7 WC Oncology SC Oncology GA MP650 UT WOS:A1994MP65000008 PM 7505830 ER PT J AU MAYNE, ST JANERICH, DT GREENWALD, P CHOROST, S TUCCI, C ZAMAN, MB MELAMED, MR KIELY, M MCKNEALLY, MF AF MAYNE, ST JANERICH, DT GREENWALD, P CHOROST, S TUCCI, C ZAMAN, MB MELAMED, MR KIELY, M MCKNEALLY, MF TI DIETARY BETA-CAROTENE AND LUNG-CANCER RISK IN UNITED-STATES NONSMOKERS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID VITAMIN-A; CONSUMPTION; SMOKING; HAWAII; FAT AB Background: Approximately 15% of all lung cancer deaths in the United States (about 22350 deaths annually) may not be directly attributable to active cigarette smoking. Consumption of beta carotene, which is derived almost exclusively from intake of fruits and vegetables, has been associated with a reduced risk of lung cancer in smokers. However, studies examining this association in nonsmokers, particularly nonsmoking men, are limited. Purpose: The purpose of this study was to examine whether dietary factors including beta carotene and retinol are associated with a reduced risk for lung cancer in nonsmoking men and women. Methods: A population-based, matched case-control study of lung cancer in nonsmokers was conducted in New York State from 1982 to 1985. Dietary interviews were completed for 413 individually matched case-control pairs of subjects. To determine whether the relationship between dietary intake from specific food groups and lung cancer differed by type of interview, smoking history, sex, age, or histologic type, we examined data on the case-control pairs from each subgroup separately. The intake of beta carotene and retinol was calculated as the weighted sum of the monthly frequencies of consumption of food items containing these nutrients, where the weights correspond to the nutrient content of a typical portion of the food items. Results: Consumption of greens (P for trend <.01), fresh fruits (P for trend <.01), and cheese (P for trend <.05) was associated with a significant dose-dependent reduction in risk for lung cancer, whereas consumption of whole milk (P for trend <.01) was associated with a significant dose-dependent increase in risk. Use of vitamin E supplements was also protective (odds ratio = 0.55; 95% confidence interval [CI] = 0.35-0.85). Increased consumption of the following food groups was associated with a reduction in risk among females: vegetables (P for trend <.025), raw fruits and vegetables (P for trend <.005), and dairy products (P for trend <.025). In males, increased consumption of raw fruits and vegetables was associated with a reduced risk for lung cancer (P for trend <.005). Dietary beta carotene (OR = 0.70; 95% CI = 0.50-0.99), but not retinol (OR = 0.98; 95% CI = 0.82-1.17), was significantly associated with risk reduction. Conclusions: This is the largest study to date of dietary factors and lung cancer in nonsmokers; results suggest that dietary beta carotene, raw fruits and vegetables, and vitamin E supplements reduce the risk of lung cancer in nonsmoking men and women. C1 UTAH CANC CTR,SALT LAKE CITY,UT. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. NEW YORK STATE DEPT HLTH,ALBANY,NY 12201. NEW YORK MED COLL,VALHALLA,NY 10595. TORONTO GEN HOSP,TORONTO M5G 1L7,ONTARIO,CANADA. RP MAYNE, ST (reprint author), YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,POB 208034,NEW HAVEN,CT 06510, USA. FU NCI NIH HHS [R01CA32088, R03CA48389] NR 28 TC 138 Z9 139 U1 1 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 JAN 5 PY 1994 VL 86 IS 1 BP 33 EP 38 DI 10.1093/jnci/86.1.33 PG 6 WC Oncology SC Oncology GA MP650 UT WOS:A1994MP65000011 PM 8271280 ER PT J AU COLE, DJ SANDA, MG YANG, JC SCHWARTZENTRUBER, DJ WEBER, J ETTINGHAUSEN, SE POCKAJ, BA KIM, HI LEVIN, RD POGREBNIAK, HW BALKISSOON, J FENTON, RM DEBARGE, LR KAYE, J ROSENBERG, SA PARKINSON, DR AF COLE, DJ SANDA, MG YANG, JC SCHWARTZENTRUBER, DJ WEBER, J ETTINGHAUSEN, SE POCKAJ, BA KIM, HI LEVIN, RD POGREBNIAK, HW BALKISSOON, J FENTON, RM DEBARGE, LR KAYE, J ROSENBERG, SA PARKINSON, DR TI PHASE-I TRIAL OF RECOMBINANT HUMAN MACROPHAGE-COLONY-STIMULATING FACTOR ADMINISTERED BY CONTINUOUS INTRAVENOUS-INFUSION IN PATIENTS WITH METASTATIC CANCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID GROWTH-FACTOR; MONOCLONAL-ANTIBODIES; MURINE MACROPHAGES; FACTOR CSF-1; HUMAN-MONOCYTES; TUMOR-CELLS; INDUCTION; CYTOTOXICITY; RECEPTOR; RELEASE AB Background: Macrophage colony-stimulating factor is a bone marrow-derived glycoprotein that can stimulate monocytes and macrophages, resulting in production of factors involved in immune response. In vitro and in vivo preclinical studies in animals have demonstrated that recombinant human macrophage colony-stimulating factor (rHuM-CSF) can have antitumor activity. Purpose: A phase I clinical trial was undertaken to evaluate the toxicity, pharmacokinetics, and immunologic effects of rHuM-CSF given by continuous intravenous infusion in patients with cancer. Methods: Eighteen patients with metastatic solid tumors refractory to conventional therapy were treated with rHuM-CSF. Twelve patients received two 14-day cycles of rHuM-CSF by continuous infusion, with a 2-week interval. Dose escalation levels were 50, 100, and 150 mug/kg over 24 hours. Consecutive cohorts of three to six patients were planned at each dose level. Six patients received a modified regimen of four 7-day periods of infusion at 100 mug/kg over 24 hours, with 1-week intervals. Results: Dose-limiting toxicity was grade 4 thrombocytopenia at a dose of 150 mug/kg over 24 hours in two patients receiving the 2-week regimen. Platelet count nadirs and concomitant monocytosis were seen on days 7-9, but recovery occurred during the treatment period. Macrophage colony-serum levels were maximal on day 1 and returned to near baseline on day 7 of infusion. Patients treated with four 7-day infusions had no treatment-limiting thrombocytopenia. There were no cumulative effects on platelet or monocyte counts or significant constitutional symptoms. Subclinical conjunctival injection was noted in rive of 10 patients receiving screening ophthalmologic evaluation. Grade 2 episcleritis was diagnosed in one patient, and asymptomatic perilimbal and retinal hemorrhages were seen in two. Two patients developed sepsis caused by the intravenous line, which required cessation of therapy. No objective responses were documented. Conclusion: The maximum tolerated dose of rHuM-CSF given by continuous intravenous infusion for 14 days was 100 mug/kg over 24 hours, with rapidly reversible, dose-limiting thrombocytopenia at 150 mug/kg over 24 hours. A regimen alternating weekly cycles of infusion avoids dose-limiting toxicity and allows long-term treatment. Implications: The regimen of repeated 7-day infusions may be useful for future studies evaluating rHuM-CSF-activated monocytes in therapy for long-term infectious diseases or in investigation of new modes of cancer therapy using rHuM-CSF in conjunction with a tumor-specific antibody. C1 NEI,BETHESDA,MD 20892. GENET INST INC,CAMBRIDGE,MA. RP COLE, DJ (reprint author), NCI,DIV CANC TREATMENT,BLDG 10,ROOM 2B42,BETHESDA,MD 20892, USA. RI Sanda, Martin/A-6202-2013; Sanda, Martin/B-2023-2015 NR 32 TC 14 Z9 15 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 5 PY 1994 VL 86 IS 1 BP 39 EP 45 DI 10.1093/jnci/86.1.39 PG 7 WC Oncology SC Oncology GA MP650 UT WOS:A1994MP65000012 PM 8271281 ER PT J AU SPANGRUDE, GJ AF SPANGRUDE, GJ TI ISOLATION AND BIOLOGY OF HEMATOPOIETIC STEM-CELLS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIAID,ROCKY MT LABS,HAMILTON,MT 59840. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 2 EP 2 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200001 ER PT J AU YOUNG, NS BROWN, K GALLINELLA, G KAJIGAYA, S MIYAMURA, K MOMOEDA, M AF YOUNG, NS BROWN, K GALLINELLA, G KAJIGAYA, S MIYAMURA, K MOMOEDA, M TI PARVOVIRUSES IN BONE-MARROW FAILURE SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 8 EP 8 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200020 ER PT J AU KELLER, JR RUSCETTI, FW ORTIZ, M GOOYA, JM JACOBSEN, SEW AF KELLER, JR RUSCETTI, FW ORTIZ, M GOOYA, JM JACOBSEN, SEW TI HEMATOPOIETIC PROGENITOR-CELL GROWTH IS DETERMINED BY THE BALANCE BETWEEN THE SYNERGISTIC EFFECTS OF MULTIPLE STIMULATORS AND THE COOPERATION OF MULTIPLE INHIBITORS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NORWEGIAN RADIUM HOSP,DEPT IMMUNOL,OSLO,NORWAY. NCI,FCRDC,LLB,BRMP,DYNCORP,PRI,BCDP,FREDERICK,MD. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 12 EP 12 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200035 ER PT J AU KMIECIK, TE RUSCETTI, FW GOOYA, JM KELLER, JR AF KMIECIK, TE RUSCETTI, FW GOOYA, JM KELLER, JR TI THE ROLE OF HEPATOCYTE GROWTH-FACTOR IN MURINE AND HUMAN HEMATOPOIESIS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NCI,FCRDC,DCT,BRMP,LLB,FREDERICK,MD. NCI,FCRDC,PRI,DYNCORP INC,FREDERICK,MD. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 12 EP 12 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200034 ER PT J AU FARNER, NL VOSS, SD LEARY, TP GAN, J FARRAR, WL EVANS, GA SONDEL, PM AF FARNER, NL VOSS, SD LEARY, TP GAN, J FARRAR, WL EVANS, GA SONDEL, PM TI POTENTIAL ROLE FOR THE IL-2 RECEPTOR-GAMMA CHAIN IN RECEPTOR COMPLEXES OF OTHER MEMBERS OF THE CYTOKINE RECEPTOR SUPERFAMILY SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 UNIV WISCONSIN,DEPT HUMAN ONCOL,MADISON,WI 53792. NCI,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 18 EP 18 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200059 ER PT J AU GOOYA, JG RUSCETTI, FW KELLER, JR AF GOOYA, JG RUSCETTI, FW KELLER, JR TI THE DIRECT SYNERGISTIC EFFECTS OF LEUKEMIA INHIBITORY FACTOR ON HEMATOPOIETIC PROGENITOR-CELL GROWTH SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NCI,FCRDC,BRMP,LLB,DYNCORP,PRI,BCDP,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 19 EP 19 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200062 ER PT J AU MCCLOSKEY, RP PIERCE, J KOSKI, R VARNUM, B LIU, F AF MCCLOSKEY, RP PIERCE, J KOSKI, R VARNUM, B LIU, F TI ACTIVATION OF THE AXL RECEPTOR TYROSINE KINASE INDUCES MITOGENESIS AND TRANSFORMATION IN 32D CELLS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 UNIV N CAROLINA,CURRICULUM GENET,CHAPEL HILL,NC. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. AMGEN CORP,THOUSAND OAKS,CA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 30 EP 30 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200102 ER PT J AU MUSZYNSKI, KW TROPPMAIR, J RUSCETTI, FW KETTER, JR AF MUSZYNSKI, KW TROPPMAIR, J RUSCETTI, FW KETTER, JR TI C-RAF ANTISENSE OLIGONUCLEOTIDE INHIBITION OF MURINE AND HUMAN HEMATOPOIETIC-CELL GROWTH SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NCI,FCRDC,LVC,LLB,BRMP,DYNCORP,PRI,BCDP,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 30 EP 30 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200104 ER PT J AU SWANSON, J AF SWANSON, J TI INFLUENCE OF SURFACE-CHARGE ON BIOLOGICAL BEHAVIOR OF NEISSERIA-GONORRHOEAE SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 38 EP 38 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200128 ER PT J AU BLUMENTHAL, R AF BLUMENTHAL, R TI HOW VIRAL ENVELOPE GLYCOPROTEINS NEGOTIATE THE ENTRY OF GENETIC MATERIAL INTO THE CELL SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract ID INITIAL-STAGES; FUSION; HEMAGGLUTININ C1 NIH,BETHESDA,MD 20892. NR 5 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 56 EP 56 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200191 ER PT J AU HARRIS, RA DWYER, DM KAYE, PM AF HARRIS, RA DWYER, DM KAYE, PM TI CHARACTERIZATION OF THE SITE OF ANTIGEN-PROCESSING IN LEISHMANIA INFECTED MACROPHAGES SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 LONDON SCH HYG & TROP MED,DEPT MED PARASITOL,LONDON WC1E 7HT,ENGLAND. NIAID,PARASIT DIS LAB,BETHESDA,MD 20205. NR 2 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 57 EP 57 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200195 ER PT J AU MERKEL, T STIBITZ, S AF MERKEL, T STIBITZ, S TI GENETIC-ANALYSIS OF VIRULENCE REGULATION IN BORDETELLA-PERTUSSIS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 US FDA,CBER,BETHESDA,MD 20892. RP MERKEL, T (reprint author), NIDR,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 66 EP 66 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200232 ER PT J AU DOHM, GL WILSON, CM CUSHMAN, SW DUDEK, RW AF DOHM, GL WILSON, CM CUSHMAN, SW DUDEK, RW TI ROLE OF TRANSVERSE TUBULES IN MUSCLE GLUCOSE-TRANSPORT SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 E CAROLINA UNIV,DEPT BIOCHEM,GREENVILLE,NC. E CAROLINA UNIV,DEPT ANAT,GREENVILLE,NC. E CAROLINA UNIV,DEPT CELL BIOL,GREENVILLE,NC. NIDDK,DIABET BRANCH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 127 EP 127 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200434 ER PT J AU BERGER, JP BISWAS, C BRADY, E CONTI, M CULLINAN, C HAYES, N MANGANIELLO, VC SAPERSTEIN, R WANG, LH LEIBOWITZ, MD AF BERGER, JP BISWAS, C BRADY, E CONTI, M CULLINAN, C HAYES, N MANGANIELLO, VC SAPERSTEIN, R WANG, LH LEIBOWITZ, MD TI A NOVEL GLUCOSE-DEPENDENT INSULIN SECRETAGOGUE IS A PHOSPHODIESTERASE INHIBITOR SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 MERCK RES LABS,RAHWAY,NJ 07065. STANFORD UNIV,PALO ALTO,CA. NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 133 EP 133 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200452 ER PT J AU POLLET, RJ ELKEBBI, I BRADSHAW, S PAO, CI PHILLIPS, LS CUSHMAN, S WILSON, C AF POLLET, RJ ELKEBBI, I BRADSHAW, S PAO, CI PHILLIPS, LS CUSHMAN, S WILSON, C TI REGULATION OF GLUCOSE-TRANSPORTER GENE-EXPRESSION - SYNTHESIS AND TRANSLOCATION IN CULTURED MUSCLE-CELLS BY INSULIN AND GLUCOSE SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 EMORY UNIV,VA MED CTR,ATLANTA,GA 30033. NIDDKD,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 136 EP 136 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200462 ER PT J AU MASTICK, CC LEROITH, D SALTIEL, AR AF MASTICK, CC LEROITH, D SALTIEL, AR TI INSULIN AND IGF-1 RECEPTORS ELICIT DIFFERENT SIGNAL-TRANSDUCTION PATHWAYS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 PARKE DAVIS PHARMACEUT RES,DEPT SIGNAL TRANSDUCT,ANN ARBOR,MI 48105. NIDDK,DIABET BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 139 EP 139 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200475 ER PT J AU LONDOS, C AF LONDOS, C TI CELLULAR AND MOLECULAR ASPECTS OF LIPID DROPLET-ASSOCIATED PERILIPINS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 154 EP 154 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200521 ER PT J AU MANGANIELLO, VC TAIRA, M LEROY, MJ KEDEV, S RASCON, A DEGERMAN, E TORNQVIST, H BELFRAGE, P AF MANGANIELLO, VC TAIRA, M LEROY, MJ KEDEV, S RASCON, A DEGERMAN, E TORNQVIST, H BELFRAGE, P TI MOLECULAR STUDIES OF INSULIN REGULATION OF LIPOLYSIS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892. LUND UNIV,DEPT PHYSIOL CHEM,LUND,SWEDEN. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 154 EP 154 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200522 ER PT J AU CUSHMAN, SW SATOH, S VANNUCCI, SJ SIMPSON, IA HOLMAN, GD AF CUSHMAN, SW SATOH, S VANNUCCI, SJ SIMPSON, IA HOLMAN, GD TI CELL BIOLOGY OF INSULIN ACTION ON GLUCOSE-TRANSPORT SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIDDK,DIABET BRANCH,BETHESDA,MD 20892. UNIV BATH,DEPT BIOCHEM,BATH BA2 7AY,AVON,ENGLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 157 EP 157 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200532 ER PT J AU SPIEGEL, AM AF SPIEGEL, AM TI MUTATIONS IN G-PROTEINS AND IN G-PROTEIN-COUPLED RECEPTORS IN HUMAN-DISEASE SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIDDKD,MOLEC PATHOPHYSIOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 157 EP 157 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200531 ER PT J AU GREENBERG, AS EGAN, JJ WEK, SA MOOS, MC KANG, YH LONDOS, C KIMMEL, AR AF GREENBERG, AS EGAN, JJ WEK, SA MOOS, MC KANG, YH LONDOS, C KIMMEL, AR TI ISOLATION OF CDNAS FOR RAT AND HUMAN PERILIPINS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 161 EP 161 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200544 ER PT J AU GRUIAGRAY, J SERVETNICK, DA GREENBERG, AS LONDOS, C KIMMEL, AR AF GRUIAGRAY, J SERVETNICK, DA GREENBERG, AS LONDOS, C KIMMEL, AR TI CHARACTERIZATION OF MURINE GENOMIC AND CDNA SEQUENCES FOR PERILIPINS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 161 EP 161 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200546 ER PT J AU BLANCHETTEMACKIE, EJ DWYER, NK BARBER, T COXEY, RA RONDINONE, CM LONDOS, C AF BLANCHETTEMACKIE, EJ DWYER, NK BARBER, T COXEY, RA RONDINONE, CM LONDOS, C TI PERILIPIN IS ON THE SURFACE-LAYER OF INTRACELLULAR LIPID DROPLETS IN ADIPOCYTES AND ADRENAL-CELLS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 166 EP 166 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200566 ER PT J AU BRASAEMLE, DL SERVETNICK, DA WOLFF, J LONDOS, C AF BRASAEMLE, DL SERVETNICK, DA WOLFF, J LONDOS, C TI PERILIPINS AT THE SURFACE OF CHOLESTERYL ESTER DROPLETS IN Y-1 ADRENAL-CORTICAL CELLS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 167 EP 167 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200567 ER PT J AU EDENS, NK LONDOS, C AF EDENS, NK LONDOS, C TI USE OF 5-[I-125]IODONAPHTHYL-1-AZIDE TO LABEL ADIPOCYTE PROTEINS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 UNIV MARYLAND,DEPT NUTR & FOOD SCI,COLL PK,MD 20742. NIDDK,MEMBRANE REGULAT SECT,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 168 EP 168 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200573 ER PT J AU RONDINONE, C TAKEDA, T BARBER, T BLANCHETTEMACKIE, EJ KIMMEL, AR GREENBERG, AS LONDOS, C AF RONDINONE, C TAKEDA, T BARBER, T BLANCHETTEMACKIE, EJ KIMMEL, AR GREENBERG, AS LONDOS, C TI ON THE RELATIONSHIP BETWEEN PERILIPINS AND TRIACYLGLYCEROL ACCUMULATION IN DIFFERENTIATING 3T3-L1 ADIPOCYTES SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 171 EP 171 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200584 ER PT J AU SERVETNICK, DA THEODORAKIS, JL BRASAEMLE, DM LONDOS, C AF SERVETNICK, DA THEODORAKIS, JL BRASAEMLE, DM LONDOS, C TI IN-VITRO TRANSLOCATION OF HORMONE-SENSITIVE LIPASE TO ADIPOCYTE LIPID STORAGE DROPLETS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 171 EP 171 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200586 ER PT J AU THEODORAKIS, JL LONDOS, C AF THEODORAKIS, JL LONDOS, C TI SOLUBILIZATION AND PURIFICATION OF PERILIPIN, A LIPID DROPLET-ASSOCIATED ADIPOCYTE PROTEIN SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 172 EP 172 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200590 ER PT J AU BLANCHETTEMACKIE, EJ DWYER, NK BARBER, T COXEY, RA RONDINONE, CM LONDOS, C AF BLANCHETTEMACKIE, EJ DWYER, NK BARBER, T COXEY, RA RONDINONE, CM LONDOS, C TI PERILIPIN IS ON THE SURFACE-LAYER OF INTRACELLULAR LIPID DROPLETS IN ADIPOCYTES AND ADRENAL-CELLS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 180 EP 180 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200616 ER PT J AU SATOH, S KRIEF, S GREENBERG, AS TAKEDA, T LONDOS, C KIMMEL, AR CUSHMAN, SW AF SATOH, S KRIEF, S GREENBERG, AS TAKEDA, T LONDOS, C KIMMEL, AR CUSHMAN, SW TI GLUCOSE-TRANSPORT, GLUCOSE-TRANSPORTER AND GLUCOSE-TRANSPORT GENE IN LONG-TERM PRIMARY CULTURE ADIPOCYTES SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 YOKOHAMA CITY UNIV,YOKOHAMA,JAPAN. NIDDK,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 180 EP 180 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200619 ER PT J AU COLLINS, FS GUTMANN, DH MITCHELL, AL DORAN, S ANDERSEN, LB GREGORY, PE HAJARA, A SWAROOP, M COLE, J AF COLLINS, FS GUTMANN, DH MITCHELL, AL DORAN, S ANDERSEN, LB GREGORY, PE HAJARA, A SWAROOP, M COLE, J TI MOLECULAR-GENETICS OF NEUROFIBROMATOSIS TYPE-1 SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIH,NATL CTR HUMAN GENOME RES,ANN ARBOR,MI. UNIV MICHIGAN,ANN ARBOR,MI 48109. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 185 EP 185 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200624 ER PT J AU EPSTEIN, CJ HUANG, TT CHAN, PH CADET, JL CARLSON, EJ AF EPSTEIN, CJ HUANG, TT CHAN, PH CADET, JL CARLSON, EJ TI THE EFFECTS OF GENETICALLY ALTERED SUPEROXIDE-DISMUTASE ACTIVITY SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA. NIDA,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 185 EP 185 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200626 ER PT J AU REEDERS, ST SCHNEIDER, MC WATERBURY, PG WEINSTATSASLOW, D BARTON, NJ SOMLO, S GERMINO, GG AF REEDERS, ST SCHNEIDER, MC WATERBURY, PG WEINSTATSASLOW, D BARTON, NJ SOMLO, S GERMINO, GG TI STRUCTURE OF 3 DISTINCT GENES THAT ENCODE WD-40 MOTIFS IN THE PKD1 REGION SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 YALE UNIV,SCH MED,DEPT INTERNAL MED,NEW HAVEN,CT 06536. YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06536. HOWARD HUGHES MED INST,NEW HAVEN,CT. NIH,BETHESDA,MD. ALBERT EINSTEIN COLL MED,BRONX,NY. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 190 EP 190 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200640 ER PT J AU GINNS, EI YOSHIKAWA, H MCKINNEY, CE STUBBLEFIELD, BK WINFIELD, S CARMON, L MARTIN, BM WILLEMSEN, R SIDRANSKY, E LAMARCA, ME AF GINNS, EI YOSHIKAWA, H MCKINNEY, CE STUBBLEFIELD, BK WINFIELD, S CARMON, L MARTIN, BM WILLEMSEN, R SIDRANSKY, E LAMARCA, ME TI PROGRESS TOWARD GENERATING TYPE-1 GAUCHER MICE BY INTRODUCTION OF THE N370S POINT MUTATION BY HOMOLOGOUS RECOMBINATION INTO ES CELLS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIMH,BR NEUROSCI CLIN,BETHESDA,MD 20892. ERASMUS UNIV ROTTERDAM,ROTTERDAM,NETHERLANDS. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 195 EP 195 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200657 ER PT J AU TEMPLETON, NS SAFER, B AF TEMPLETON, NS SAFER, B TI HOMOLOGOUS RECOMBINATION IN MOUSE EMBRYONIC STEM-CELLS WITH AN ABSOLUTE FREQUENCY OF 10(-1) SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 198 EP 198 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200670 ER PT J AU CHARNAS, L RODNEY, D NUSSBAUM, RL AF CHARNAS, L RODNEY, D NUSSBAUM, RL TI MULTIPLE NEURAL ALTERNATIVE SPLICE PRODUCTS OF OCRL-1, THE GENE CAUSING THE OCULOCEREBRORENAL SYNDROME OF LOWE SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. UNIV PENN,SCH MED,DEPT HUMAN GENET,PHILADELPHIA,PA 19104. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 199 EP 199 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200674 ER PT J AU CHIPEV, C YANG, JM DIGIOVANNA, J BALE, S COMPTON, J STEINERT, P AF CHIPEV, C YANG, JM DIGIOVANNA, J BALE, S COMPTON, J STEINERT, P TI MUTATIONS IN KERATIN-RELATED GENO-DERMATOSES ARE CLUSTERED IN MOLECULAR OVERLAP REGIONS OF KERATIN INTERMEDIATE FILAMENTS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIAMS,SKIN BIOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 199 EP 199 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200673 ER PT J AU AKSENTIJEVICH, I LEVY, E PRAS, E CHEN, X FERRIN, L KEITH, T PRAS, M KASTNER, DL AF AKSENTIJEVICH, I LEVY, E PRAS, E CHEN, X FERRIN, L KEITH, T PRAS, M KASTNER, DL TI GENETIC AND PHYSICAL MAPPING OF THE GENE FOR FAMILIAL MEDITERRANEAN FEVER (FMF) SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIAMS,ARB,BETHESDA,MD. NIDDK,GBB,BETHESDA,MD. COLLABORAT RES INC,WALTHAM,MA. SHEBA MED CTR,HELLER INST MED RES,TEL HASHOMER,ISRAEL. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 204 EP 204 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200691 ER PT J AU AVRAHAM, KB KINGSLEY, DM RUSSELL, LB COPELAND, NG JENKINS, NA AF AVRAHAM, KB KINGSLEY, DM RUSSELL, LB COPELAND, NG JENKINS, NA TI MOLECULAR-GENETIC CHARACTERIZATION OF THE DEAF SNELLS WALTZER MOUSE SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NCI,ABL,BRP,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,FREDERICK,MD 21702. STANFORD UNIV,SCH MED,DEPT DEV BIOL,STANFORD,CA 94305. OAK RIDGE NATL LAB,DIV BIOL,OAK RIDGE,TN 37831. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 204 EP 204 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200693 ER PT J AU PRAS, E ARBER, N SHAPIRO, J AKSENTIJEVICH, I KATZ, G HARELL, D LIBERMAN, U PRAS, M KASTNER, DL AF PRAS, E ARBER, N SHAPIRO, J AKSENTIJEVICH, I KATZ, G HARELL, D LIBERMAN, U PRAS, M KASTNER, DL TI LINKAGE STUDIES IN CYSTINURIA SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIAMS,ARB,BETHESDA,MD. BEILINSON MED CTR,PETAH TIQWA,ISRAEL. SHEBA MED CTR,TEL HASHOMER,ISRAEL. SHEBA MED CTR,TEL HASHOMER,ISRAEL. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 208 EP 208 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200707 ER PT J AU COLLINS, FS GUTMANN, DH MITCHELL, AL DORAN, S ANDERSEN, LB GREGORY, PE HAJARA, A SWAROOP, M COLE, J AF COLLINS, FS GUTMANN, DH MITCHELL, AL DORAN, S ANDERSEN, LB GREGORY, PE HAJARA, A SWAROOP, M COLE, J TI MOLECULAR-GENETICS OF NEUROFIBROMATOSIS TYPE-1 SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIH,NATL CTR HUMAN GENOME RES,ANN ARBOR,MI. UNIV MICHIGAN,ANN ARBOR,MI. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 215 EP 215 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200728 ER PT J AU LISZIEWICZ, J SUM, D SMYTHE, J LORI, F PENG, B TRAPNELL, B ROSSI, J GALLO, RC AF LISZIEWICZ, J SUM, D SMYTHE, J LORI, F PENG, B TRAPNELL, B ROSSI, J GALLO, RC TI GENE-THERAPY TO HIV-1 INFECTION - RNA DECOYS AND COMBINATION APPROACHES SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. JOHNSON & JOHNSON,SYDNEY,NSW,AUSTRALIA. GENET THERAPY INC,GAITHERSBURG,MD 20877. BECKMAN RES INST,DUARTE,CA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 221 EP 221 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200745 ER PT J AU CANDOTTI, F MULLEN, CA BLAESE, RM AF CANDOTTI, F MULLEN, CA BLAESE, RM TI USE OF A COMBINED POSITIVE/NEGATIVE SELECTABLE GENE FOR RETROVIRAL-MEDIATED GENE-TRANSFER SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 223 EP 223 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200752 ER PT J AU ISHII, H AGBARIA, R HIRANO, H RAM, Z OLDFIELD, E JOHNS, DG BLAESE, RM AF ISHII, H AGBARIA, R HIRANO, H RAM, Z OLDFIELD, E JOHNS, DG BLAESE, RM TI MECHANISM OF BYSTANDER EFFECT KILLING IN THE HERPES-SIMPLEX THYMIDINE KINASE GENE-MODIFIED TUMOR SYSTEM SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 226 EP 226 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200764 ER PT J AU LORI, F LISZIEWICZ, J SMYTHE, J CARA, A BUNNAG, TA CURIEL, D GALLO, RC AF LORI, F LISZIEWICZ, J SMYTHE, J CARA, A BUNNAG, TA CURIEL, D GALLO, RC TI RAPID PROTECTION AGAINST HIV-1 REPLICATION MEDIATED BY HIGH-EFFICIENCY NON-RETROVIRAL DELIVERY OF GENES INTERFERING WITH HIV-1 TAT AND GAG SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. UNIV ALABAMA,CTR COMPREHENS CANC,BIRMINGHAM,AL 35201. RI Cara, Andrea/M-4865-2015 OI Cara, Andrea/0000-0003-4967-1895 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 227 EP 227 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200769 ER PT J AU RITCHEY, DW HALL, ER KAUSHAL, S LARUSSA, V KESSLER, S GARTNER, S STLOUIS, DC MAYERS, D PERERA, LP YU, ZP KIM, JH SITZ, K XU, J BURKE, DS MOSCA, JD AF RITCHEY, DW HALL, ER KAUSHAL, S LARUSSA, V KESSLER, S GARTNER, S STLOUIS, DC MAYERS, D PERERA, LP YU, ZP KIM, JH SITZ, K XU, J BURKE, DS MOSCA, JD TI DEVELOPING A MICROENVIRONMENT FOR THE DIFFERENTIATION OF PRIMITIVE CD34+ HEMATOPOIETIC-CELLS IN HU-BM-SCID MICE SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 JACKSON FDN,ROCKVILLE,MD. WRAIR,ROCKVILLE,MD. NIH,BETHESDA,MD. NMRI,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 234 EP 234 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200798 ER PT J AU CHUAH, M VANDENDRIESSCHE, T NEWMAN, K MULLEN, C MORGAN, R AF CHUAH, M VANDENDRIESSCHE, T NEWMAN, K MULLEN, C MORGAN, R TI DEVELOPMENT AND ANALYSIS OF RETROVIRAL VECTORS EXPRESSING HUMAN FACTOR-VIII AND FACTOR-IX AS A POTENTIAL GENE-THERAPY FOR HEMOPHILIA SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD. NCI,BETHESDA,MD. NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 236 EP 236 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200806 ER PT J AU KOH, GY KIM, SJ KLUG, MG PARK, K SOONPAA, MH WANG, H FIELD, LJ AF KOH, GY KIM, SJ KLUG, MG PARK, K SOONPAA, MH WANG, H FIELD, LJ TI LOCAL, LONG-TERM DELIVERY OF RECOMBINANT SECRETORY FORM OF TGF-B1 TO THE MYOCARDIUM BY USING SOMATIC GENE-TRANSFER SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 INDIANA UNIV,SCH MED,DEPT MED,INDIANAPOLIS,IN 46202. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 238 EP 238 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200813 ER PT J AU KOHN, DB WEINBERG, KI PARKMAN, R LENARSKY, C CROOKS, GM SHAW, K HANLEY, ME LAWRENCE, K ANNETT, G BROOKS, JS WARA, D ELDER, M BOWEN, T HERSHFIELD, MS BERENSON, RI MOEN, RC MULLEN, CA BLAESE, RM AF KOHN, DB WEINBERG, KI PARKMAN, R LENARSKY, C CROOKS, GM SHAW, K HANLEY, ME LAWRENCE, K ANNETT, G BROOKS, JS WARA, D ELDER, M BOWEN, T HERSHFIELD, MS BERENSON, RI MOEN, RC MULLEN, CA BLAESE, RM TI GENE-THERAPY FOR NEONATES WITH ADA-DEFICIENT SCID BY RETROVIRAL-MEDIATED TRANSFER OF THE HUMAN ADA CDNA INTO UMBILICAL-CORD CD34+ CELLS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 CHILDRENS HOSP LOS ANGELES,LOS ANGELES,CA. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA. CALGARY CHILDRENS HOSP,CALGARY,AB,CANADA. DUKE UNIV,DURHAM,NC. GENET THERAPY INC,GAITHERSBURG,MD. NCI,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 238 EP 238 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200812 ER PT J AU MUHLHAUSER, J MERRILL, MJ MAEDA, H BACIC, M CRYSTAL, RG CAPOGROSSI, MC AF MUHLHAUSER, J MERRILL, MJ MAEDA, H BACIC, M CRYSTAL, RG CAPOGROSSI, MC TI VEGF GENE-TRANSFER INTO VASCULAR SMOOTH-MUSCLE AND ENDOTHELIAL-CELLS WITH A REPLICATION-DEFICIENT RECOMBINANT ADENOVIRUS VECTOR SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NHLBI,PULM BRANCH,BETHESDA,MD 20892. NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 239 EP 239 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200818 ER PT J AU MULLEN, CA SNITZER, K BLAESE, RM AF MULLEN, CA SNITZER, K BLAESE, RM TI LONG-TERM IN-VIVO EXPRESSION OF RETROVIRALLY TRANSFERRED ADA GENES IN LYMPHOCYTE CLONES FROM AN ADA-SCID PATIENT TREATED WITH GENE-THERAPY SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NCI,MED BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 240 EP 240 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200819 ER PT J AU BAIER, L SACCHETTINI, J BOGARDUS, C PROCHAZKA, M AF BAIER, L SACCHETTINI, J BOGARDUS, C PROCHAZKA, M TI AN ALANINE TO THREONINE SUBSTITUTION IN THE INTESTINAL FATTY-ACID-BINDING PROTEIN IS ASSOCIATED WITH INSULIN SENSITIVITY AND OBESITY IN MEN SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIH,CLIN DIABET & NUTR SECT,PHOENIX,AZ 85016. ALBERT EINSTEIN COLL MED,BRONX,NY 10461. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 241 EP 241 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200824 ER PT J AU MORGAN, RA RAGHEB, J CHUAH, M VANDENDRIESSCHE, T BRESSLER, P AF MORGAN, RA RAGHEB, J CHUAH, M VANDENDRIESSCHE, T BRESSLER, P TI DEVELOPMENT OF RETROVIRAL VECTORS THAT OPTIMIZE THE INHIBITION OF HIV-1 AT MULTIPLE POINTS OF THE VIRAL LIFE-CYCLE SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 243 EP 243 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200833 ER PT J AU BERNSTEIN, SL AF BERNSTEIN, SL TI VARIATION IN RIBOZYME ACTIVITY AGAINST INTERPHOTORECEPTOR RETINOID-BINDING PROTEIN (IRBP) MESSENGER-RNA BY SITE AND COMPLEMENT LENGTH SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIH,NEI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 245 EP 245 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200839 ER PT J AU TORNATORE, C MEYERS, K MAJOR, G AF TORNATORE, C MEYERS, K MAJOR, G TI CAN JC VIRUS BE USED AS A VECTOR FOR GENE DELIVERY TO OLIGODENDROCYTES AND ASTROCYTES OF THE CNS WHITE-MATTER SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIH,MOLEC VIROL & GENET SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 247 EP 247 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200847 ER PT J AU KRALL, W CHALLITA, PM NOLTA, JA RIVIERE, I LEHN, P GINNS, EI MULLIGAN, RC KOHN, DB AF KRALL, W CHALLITA, PM NOLTA, JA RIVIERE, I LEHN, P GINNS, EI MULLIGAN, RC KOHN, DB TI DIRECT COMPARISON OF AN MFG-BASED VECTOR TO AN N2-BASED VECTOR IN PRIMARY HEMATOPOIETIC-CELLS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 CHILDRENS HOSP LOS ANGELES,LOS ANGELES,CA. NIMH,BETHESDA,MD. WHITEHEAD INST,CAMBRIDGE,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 251 EP 251 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200862 ER PT J AU LAKATTA, EG PAULY, RR BILATO, C FREDMAN, J CHIN, MT SUZUKI, T CROW, MT AF LAKATTA, EG PAULY, RR BILATO, C FREDMAN, J CHIN, MT SUZUKI, T CROW, MT TI THE INTRACELLULAR SIGNALING PATHWAY FOR PDGF-STIMULATED MIGRATION OF VASCULAR SMOOTH-MUSCLE CELLS REQUIRES OF CALCIUM/CALMODULIN-DEPENDENT PROTEIN-KINASE-II SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIA,BALTIMORE,MD 21224. NAGOYA CITY MED SCH,NAGOYA,AICHI,JAPAN. NR 0 TC 0 Z9 0 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 JAN 4 PY 1994 SU 18A BP 269 EP 269 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200914 ER PT J AU SAMANIEGO, F GALLO, RC ENSOLI, B AF SAMANIEGO, F GALLO, RC ENSOLI, B TI INFLAMMATORY CYTOKINES INDUCE AIDS-KAPOSIS SARCOMA-DERIVED CELLS TO RELEASE BASIC FIBROBLAST GROWTH-FACTOR SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RI Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 287 EP 287 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200982 ER PT J AU TAKEYA, M YOSHIMURA, T LEONARD, EJ TAKAHASHI, K AF TAKEYA, M YOSHIMURA, T LEONARD, EJ TAKAHASHI, K TI CHARACTERIZATION OF MONOCYTE CHEMOATTRACTANT PROTEIN-1-PRODUCING CELLS IN ATHEROSCLEROTIC LESIONS BY DOUBLE IMMUNOHISTOCHEMICAL STAINING SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 KUMAMOTO UNIV,SCH MED,DEPT PATHOL 2,KUMAMOTO 860,JAPAN. NCI,FCRDC,IMMUNOPATHOL SECT,IMMUNOBIOL LAB,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 288 EP 288 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200986 ER PT J AU YOSHIMURA, T AF YOSHIMURA, T TI GUINEA-PIG, AS AN ANIMAL-MODEL TO STUDY THE ROLE OF NEUTROPHIL ATTRACTANT PROTEIN-1 (NAP-1/IL-8) AND MONOCYTE CHEMOATTRACTANT PROTEIN-1 (MCP-1) SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NCI,FCRDC,IMMUNOPATHOL SECT,IMMUNOBIOL LAB,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 289 EP 289 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41200988 ER PT J AU PAULY, RR MONTICONE, R BILATO, C LAKATTA, E CROW, MT AF PAULY, RR MONTICONE, R BILATO, C LAKATTA, E CROW, MT TI THE MIGRATION OF VASCULAR SMOOTH-MUSCLE CELLS THROUGH A RECONSTITUTED BASEMENT-MEMBRANE REQUIRES 72 KD TYPE-IV COLLAGENASE AND IS SUPPRESSED BY CELLULAR-DIFFERENTIATION SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NIA,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 298 EP 298 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41201024 ER PT J AU ENSOLI, B MARKHAM, P KAO, V RAFFELD, M GENDELMAN, R BARILLARI, G ZON, G GALLO, RC AF ENSOLI, B MARKHAM, P KAO, V RAFFELD, M GENDELMAN, R BARILLARI, G ZON, G GALLO, RC TI BASIC FIBROBLAST GROWTH-FACTOR (BFGF) INDUCES LESIONS IN MICE RESEMBLING KAPOSIS-SARCOMA (KS) AND ANTISENSE OLIGONUCLEOTIDES AGAINST THIS CYTOKINE INHIBIT THE GROWTH AND ANGIOGENIC ACTIVITY OF KS SPINDLE CELLS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. ADV BIOSCI LABS,KENSINGTON,MD 20895. LYNX THERAPEUT INC,FOSTER CITY,CA 94404. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 327 EP 327 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41201117 ER PT J AU PILI, R MUHLHAUSER, J MERRILL, MJ MAEDA, H CHANG, J PASSANITI, T CRYSTAL, RG CAPOGROSSI, MC AF PILI, R MUHLHAUSER, J MERRILL, MJ MAEDA, H CHANG, J PASSANITI, T CRYSTAL, RG CAPOGROSSI, MC TI ADENOVIRUS-MEDIATED GENE-TRANSFER INTO VASCULAR ENDOTHELIAL-CELLS OF RECOMBINANT SECRETED AND NON-SECRETED FORMS OF ACIDIC FIBROBLAST GROWTH-FACTOR SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NHLBI,PULM BRANCH,BETHESDA,MD 20892. NIA,BIOL CHEM LAB,BETHESDA,MD 20892. NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 4 PY 1994 SU 18A BP 328 EP 328 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV412 UT WOS:A1994MV41201120 ER PT J AU BILSKI, P CHIGNELL, CF AF BILSKI, P CHIGNELL, CF TI PROPERTIES OF DIFFERENTLY CHARGED MICELLES CONTAINING ROSE-BENGAL - APPLICATION IN PHOTOSENSITIZATION STUDIES SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY LA English DT Article ID SINGLET MOLECULAR-OXYGEN; XANTHENE DYES; PICOSECOND FLUORESCENCE; AQUEOUS INTERFACES; REVERSE MICELLES; QUANTUM YIELD; SURFACTANT; SYSTEMS; SOLVENT; PHOTOCHEMISTRY AB We have studied rose bengal (RB) in micelles carrying a positive charge (cetylpyridinium chloride (CPC) and benzalkonium chloride (BC)), a neutral charge (Triton X-100 and zwitterionic lauryl sulfobetaine (SB-12)) and a negative charge (mixture of SB-12 and sodium dodecyl sulfate (SDS)). Spectral changes during RB titration with surfactant in aqueous solution (P. Bilski, R. Dabestani and C.F. Chignell, J. Phys. Chem., 95 (1991) 5784) allowed us to measure the aggregation numbers of micelles hosting RB, and to estimate the critical micelle concentrations (cmc) of the surfactants. The aggregation numbers are 37 for CPC, 41 for SB-12, 48 for Triton X-100 and 52 for mixed (6-4) SDS-SB-12 micelles, and the respective cmc are 0.22, 2.88, 0.3 and 0.5 mM. From its spectral properties in all the micelles studied, the RB molecule was found to be situated in hydrophobic micellar regions rather than adsorbed at the micellar surface. The micellar location of RB was also confirmed by quenching studies of RB fluorescence using the pyrogallol moiety, which was located outside the micelles (gallic acid), dissolved/adsorbed in the micelles (pyrogallol) or sited at the micellar interface (lauryl gallate). Lauryl gallate did not quench RB fluorescence efficiently despite the location of the pyrogallol moiety at the micellar interface. In contrast, lauryl gallate was an efficient quencher of RB fluorescence in homogeneous solution. Irrespective of the micelle charge, micellar RB was more resistant to photobleaching than ''free'' RB and produced singlet oxygen efficiently. In cationic micelles RB was insensitive to acidic pH, which may extend the usefulness of the dye as a O-1(2) generator to acidic aqueous solutions (from pH 1.5 to 5) where ''free'' RB forms a colorless lactam. RB located in micelles bearing different charges may prove useful for studying O-1(2) reactions in the aqueous phase while the RB triplet state remains sequestered in the micelles. RP BILSKI, P (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 52 TC 28 Z9 28 U1 2 U2 8 PU ELSEVIER SCIENCE SA LAUSANNE PI LAUSANNE 1 PA PO BOX 564, 1001 LAUSANNE 1, SWITZERLAND SN 1010-6030 J9 J PHOTOCH PHOTOBIO A JI J. Photochem. Photobiol. A-Chem. PD JAN 4 PY 1994 VL 77 IS 1 BP 49 EP 58 PG 10 WC Chemistry, Physical SC Chemistry GA MQ114 UT WOS:A1994MQ11400008 ER PT J AU LI, YX RINZEL, J KEIZER, J STOJILKOVIC, SS AF LI, YX RINZEL, J KEIZER, J STOJILKOVIC, SS TI CALCIUM OSCILLATIONS IN PITUITARY GONADOTROPHS - COMPARISON OF EXPERIMENT AND THEORY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; POOL DEPLETION; CYTOSOLIC CA2+; LUMINAL CA2+; MATHEMATICAL MODELING ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; ENDOPLASMIC-RETICULUM; LAEVIS OOCYTES; CA-2+; RELEASE; CELLS; CA2+; TRISPHOSPHATE; PROTEIN; MODEL AB We have developed a mathematical model that describes several aspects of agonist-induced Ca2+ signaling in single pituitary gonadotrophs. Our model is based on fast activation of the inositol 1,4,5-trisphosphate (InsP3) receptor Ca2+ channels at low free cytosolic Ca2+ concentration ([Ca2+]i) and slow inactivation at high [Ca2+]i. Previous work has shown that these gating properties, when combined with a Ca2+-ATPase, are sufficient to generate simulated Ca2+ oscillations. The Hodgkin-Huxley-like description we formulate here incorporates these different gating properties explicitly and renders their effects transparent and easy to modulate. We introduce regulatory mechanisms of channel opening which enable the model, both in the absence and in the presence of Ca2+ entry, to give responses to a wide range of agonist doses that are in good agreement with experimental findings, including subthreshold responses, superthreshold oscillations with frequency determined by [InsP3], and nonoscillatory ''biphasic'' responses followed occasionally by small-amplitude oscillations. A particular added feature of our model, enhanced channel opening by reduced concentration of Ca2+ in the lumen of the endoplasmic reticulum, allows oscillations to continue during pool depletion. The model predicts that ionomycin and thapsigargin can induce oscillations with basal [InsP3] and zero Ca2+ entry, while Ca2+ injection cannot. Responses to specific pairings of sub- or superthreshold stimuli of agonist, ionomycin, and thapsigargin are also correctly predicted. Since this model encompasses a wide range of observed dynamic behaviors within a single framework, based on well-established mechanisms, its relevance should not be restricted to gonadotrophs. C1 UNIV CALIF DAVIS,INST THEORET DYNAM,DAVIS,CA 95616. UNIV CALIF DAVIS,DEPT CHEM,DAVIS,CA 95616. NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. RP LI, YX (reprint author), NIDDKD,MATH RES BRANCH,BLDG 31,ROOM 4B54,BETHESDA,MD 20892, USA. NR 32 TC 71 Z9 73 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 4 PY 1994 VL 91 IS 1 BP 58 EP 62 DI 10.1073/pnas.91.1.58 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MQ479 UT WOS:A1994MQ47900012 PM 8278407 ER PT J AU POLI, G KINTER, AL FAUCI, AS AF POLI, G KINTER, AL FAUCI, AS TI INTERLEUKIN-1 INDUCES EXPRESSION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS ALONE AND IN SYNERGY WITH INTERLEUKIN-6 IN CHRONICALLY INFECTED U1 CELLS - INHIBITION OF INDUCTIVE EFFECTS BY THE INTERLEUKIN-1 RECEPTOR ANTAGONIST SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CYTOKINES; NF-KAPPA-B; LATENCY ID TUMOR-NECROSIS-FACTOR; LONG TERMINAL REPEAT; NF-KAPPA-B; FACTOR-ALPHA; HIV-INFECTION; GENE-EXPRESSION; T-CELLS; MACROPHAGES; CYTOKINES; ACTIVATION AB In the present study we have observed that interleukin (IL) 1alpha or IL-1beta directly induced expression of human immunodeficiency virus (HIV) in the latently infected human promonocytic cell line U1. In addition, IL-1 synergized with IL-6, but not with tumor necrosis factor, in the upregulation of virus expression in U1 cells as measured by accumulation of steady-state mRNAs and production of reverse transcriptase activity. The HIV inductive effect of IL-1 was blocked by transforming growth factor beta, anti-IL-1 antibodies, or monoclonal antibodies directed to the type 1, but not to the type 2, cell surface receptor for IL-1; the latter actually caused enhancement of the IL-1-mediated effect. Unlike tumor necrosis factor alpha, IL-1 either alone or in combination with IL-6 did not induce activation of the transcription activating factor NF-kappaB above the constitutive levels of unstimulated U1 cells. Finally, the IL-1 receptor antagonist effectively blocked IL-1-mediated direct and synergistic inductive effects on virus production. Thus, IL-1 may be an important mediator of HIV expression, and blocking of IL-1 expression and/or its effects may have a potential therapeutic role in the inhibition of HIV expression in infected individuals. RP POLI, G (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10A,ROOM 6A33A,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 36 TC 158 Z9 160 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 4 PY 1994 VL 91 IS 1 BP 108 EP 112 DI 10.1073/pnas.91.1.108 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MQ479 UT WOS:A1994MQ47900022 PM 7506410 ER PT J AU BALASUNDARAM, D DINMAN, JD WICKNER, RB TABOR, CW TABOR, H AF BALASUNDARAM, D DINMAN, JD WICKNER, RB TABOR, CW TABOR, H TI SPERMIDINE DEFICIENCY INCREASES +1 RIBOSOMAL FRAMESHIFTING EFFICIENCY AND INHIBITS TY1 RETROTRANSPOSITION IN SACCHAROMYCES-CEREVISIAE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID STRANDED-RNA VIRUS; S-ADENOSYLMETHIONINE DECARBOXYLASE; YEAST; POLYAMINES; PSEUDOKNOT; PROTEIN; GENES; PROPAGATION; REQUIREMENT; TRANSPOSON AB Polyamines have been implicated in nucleic acid-related functions and in protein biosynthesis. RNA sequences that specifically direct ribosomes to shift reading frame in the -1 and +1 directions may be used to probe the mechanisms controlling translational fidelity. We examined the effects of spermidine on translational fidelity by an in vivo assay in which changes in beta-galactosidase activity are dependent on yeast retrovirus Ty +1 and yeast double-stranded RNA virus L-A -1 ribosomal frameshifting signals. In spe2DELTA mutants of Saccharomyces cerevisiae, which cannot make spermidine as a result of a deletion in the SPE2 gene, there is a marked elevation in +1 but no change in -1 ribosomal frameshifting. The increase in +1 ribosomal frameshifting efficiency is accompanied by a striking decrease in Ty1 retrotransposition. RP BALASUNDARAM, D (reprint author), NIDDKD, BIOCHEM PHARMACOL LAB, BETHESDA, MD 20892 USA. OI Dinman, Jonathan/0000-0002-2402-9698 NR 48 TC 55 Z9 57 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 4 PY 1994 VL 91 IS 1 BP 172 EP 176 DI 10.1073/pnas.91.1.172 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MQ479 UT WOS:A1994MQ47900035 PM 8278359 ER PT J AU GLADYSHEV, VN KHANGULOV, SV STADTMAN, TC AF GLADYSHEV, VN KHANGULOV, SV STADTMAN, TC TI NICOTINIC-ACID HYDROXYLASE FROM CLOSTRIDIUM-BARKERI - ELECTRON-PARAMAGNETIC-RESONANCE STUDIES SHOW THAT SELENIUM IS COORDINATED WITH MOLYBDENUM IN THE CATALYTICALLY ACTIVE SELENIUM-DEPENDENT ENZYME SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SELENOENZYME; MO(V) ELECTRON PARAMAGNETIC RESONANCE SIGNAL; MOLYBDOPTERIN; FES CLUSTERS; LABILE SELENIUM ID FORMATE DEHYDROGENASE; PSEUDOMONAS-CARBOXYDOVORANS; XANTHINE DEHYDROGENASE; BIOCHEMISTRY; SELENOCYSTEINE; MOLYBDOENZYMES; SPECTROSCOPY; MECHANISM; KINETICS; BINDING AB Nicotinic acid hydroxylase from Clostridium barkeri contains selenium in an unidentified form that is dissociated as a low molecular weight compound upon denaturation of the enzyme. Other cofactors of this enzyme are molybdopterin, FAD, and iron-sulfur clusters. In the current study, we show that the enzyme, as isolated, exhibits a stable Mo(V) electron paramagnetic resonance (EPR) signal (''resting'' signal) and that this signal is correlated with the selenium content and nicotinate hydroxylase activity of the enzyme. Substitution of Se-77 for normal selenium isotope abundance results in splitting of the Mo(V) EPR signal of the native protein without affecting the iron signals of the FeS clusters. The Mo(V) EPR signal and nicotinic acid hydroxylase activity of enzyme isolated from cells grown in selenium-deficient medium are barely detectable. In contrast, the EPR signals of the FeS clusters, the electronic absorption spectrum, the NADPH oxidase activity, and the chromatographic behavior are changed little and are typical of active selenium-containing enzyme. An EPR signal indicative of the presence of molybdenum in the selenium-deficient enzyme also is exhibited. From these results, we conclude that a dissociable selenium moiety is coordinated directly with molybdenum in the molybdopterin cofactor and, moreover, this selenium is essential for nicotinic acid hydroxylase activity. C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NR 26 TC 53 Z9 53 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 JAN 4 PY 1994 VL 91 IS 1 BP 232 EP 236 DI 10.1073/pnas.91.1.232 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MQ479 UT WOS:A1994MQ47900048 PM 8278371 ER PT J AU LEIKIN, S RAU, DC PARSEGIAN, VA AF LEIKIN, S RAU, DC PARSEGIAN, VA TI DIRECT MEASUREMENT OF FORCES BETWEEN SELF-ASSEMBLED PROTEINS - TEMPERATURE-DEPENDENT EXPONENTIAL FORCES BETWEEN COLLAGEN TRIPLE HELICES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DNA DOUBLE HELICES; HYDRATION FORCES; PHOSPHOLIPID-BILAYERS; INTERMOLECULAR FORCES; FIBRILS; PACKING; WATER AB We report direct measurements of force vs. separation between self-assembled proteins. These forces are observed between collagen triple helices in native and reconstituted fibers. They are a combination of a short-range repulsion, which varies exponentially over at least five decay lengths, and an inferred, longer-ranged attraction responsible for spontaneous assembly. From 5-degrees-C to 35-degrees-C the relative contribution of the attraction to the net force increases with temperature. These forces are strikingly similar to the ''hydration'' forces measured between several other linear macromolecules (DNA, polysaccharides) and between lipid bilayer membranes. The decay length of the repulsive force agrees well with a theoretical estimate based on axial periodicity of the triple helix, suggesting another connection between molecular architecture and protein-protein interaction. C1 NIDDKD, BIOCHEM & METAB LAB, BETHESDA, MD 20892 USA. RP NIDDKD, DIV COMP RES & TECHNOL, STRUCT BIOL LAB, BLDG 12A, ROOM 2041, BETHESDA, MD 20892 USA. RI Leikin, Sergey/A-5518-2008 OI Leikin, Sergey/0000-0001-7095-0739 NR 35 TC 120 Z9 121 U1 0 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 4 PY 1994 VL 91 IS 1 BP 276 EP 280 DI 10.1073/pnas.91.1.276 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MQ479 UT WOS:A1994MQ47900057 PM 8278378 ER PT J AU MULARD, LA KOVAC, P GLAUDEMANS, CPJ AF MULARD, LA KOVAC, P GLAUDEMANS, CPJ TI SYNTHESIS OF LIGANDS RELATED TO THE O-SPECIFIC ANTIGEN OF SHIGELLA-DYSENTERIAE TYPE-1 .6. SYNTHESIS OF METHYL O-ALPHA-L-RHAMNOPYRANOSYL-(1 -] 2)-ALPHA-D-GALACTOPYRANOSIDES SPECIFICALLY DEOXYGENATED AT POSITION-3, POSITION-4, OR POSITION-6 OF THE GALACTOSE RESIDUE SO CARBOHYDRATE RESEARCH LA English DT Article ID PROTECTING-GROUP; DERIVATIVES; SUGARS; LIPOPOLYSACCHARIDE; POLYSACCHARIDE; TRISACCHARIDE; DISACCHARIDE; ANTIBODIES; CHLORIDE; (1->6)-BETA-D-GALACTO-OLIGOSACCHARIDES AB The title disaccharides were synthesized by condensation of 2,3,4-tri-O-benzoyl-a -L-rhamnopyranosyl bromide with suitably protected, deoxygenated derivatives of methyl alpha-D-galactopyranoside. Deoxygenation was achieved via activation of a protected methyl alpha-D-gluco- or galacto-pyranoside with N,N'-thiocarbonyldiimidazole followed by treatment with tributyltin hydride and azobisisobutyronitrile. At position 3, the deoxygenation was more successful when performed with the tri-O-benzoylated precursor, rather than the tri-O-benzylated one. The corresponding nucleophile was obtained by benzylidenation of the methyl 3-deoxy-alpha-D-xylo-hexopyranoside. The preparation of the glycosyl acceptor deoxygenated at position 4 could be pursued starting from derivatives having either the D-galacto or the D-gluco configuration. The pathway involving the former was found superior. C1 NIDDK,BETHESDA,MD 20892. NR 49 TC 17 Z9 17 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD JAN 3 PY 1994 VL 251 BP 213 EP 232 DI 10.1016/0008-6215(94)84287-6 PG 20 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA MV297 UT WOS:A1994MV29700016 PM 7511986 ER PT J AU KEARSE, KP SINGER, A AF KEARSE, KP SINGER, A TI ISOLATION OF IMMATURE AND MATURE T-CELL RECEPTOR COMPLEXES BY LECTIN AFFINITY-CHROMATOGRAPHY SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE TCR COMPLEX; LECTIN; WHEAT GERM AGGLUTININ; SIALIC ACID; ENDOGLYCOSIDASE H ID ASPARAGINE-LINKED OLIGOSACCHARIDES; ANTIGEN RECEPTOR; MONOCLONAL-ANTIBODY; ZETA-CHAIN; IDENTIFICATION; PURIFICATION; RECOGNITION; EXPRESSION AB The antigen-specific T cell receptor (TCR) is a multisubunit complex composed of at least six different polypeptide chains (alpha,beta,gamma,delta,epsilon,zeta), several of which are glycoproteins. Assembly of the TCR occurs in the endoplasmic reticulum (ER) and involves intermediary complexes of CD3-gamma,delta,epsilon proteins and TCR alpha and -beta molecules. Egress of TCR from the ER and transport through the Golgi apparatus is most often monitored by the sensitivity of TCR glycoproteins to endoglycosidase H (Endo H), an enzyme specific for immature oligosaccharides which have not yet been processed by Golgi glycosidases and glycosyltransferases. Because they are not glycosylated, the subcellular localization of CD3-epsilon and TCR zeta chains cannot be directly determined by Endo H treatment, and therefore must be inferred by association with glycoprotein members of the TCR complex. Thus, when both immature and mature TCR glycoproteins are present within a given sample, this becomes extremely difficult. In this report, we describe a method for the physical separation of immature and mature murine TCR complexes based on processing of N-linked carbohydrate side chains. Specifically, we report the use of wheat germ agglutinin-affinity matrices to separate TCR complexes which have reached the trans Golgi compartment of the cell from those that have not. This technique is rapid, sensitive, and does not affect the integrity of assembled TCR complexes. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NR 20 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JAN 3 PY 1994 VL 167 IS 1-2 BP 75 EP 81 DI 10.1016/0022-1759(94)90076-0 PG 7 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA MU314 UT WOS:A1994MU31400008 PM 8308288 ER PT J AU SALLIE, R AF SALLIE, R TI A NEW CLASSIFICATION OF ACUTE-PANCREATITIS SO MEDICAL JOURNAL OF AUSTRALIA LA English DT Letter RP SALLIE, R (reprint author), NIDDKD,LIVER DIS SECT,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AUSTRALASIAN MED PUBL CO LTD PI SYDNEY PA LEVEL 1, 76 BERRY ST, SYDNEY NSW 2060, AUSTRALIA SN 0025-729X J9 MED J AUSTRALIA JI Med. J. Aust. PD JAN 3 PY 1994 VL 160 IS 1 BP 48 EP 48 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA MP927 UT WOS:A1994MP92700031 PM 8123142 ER PT J AU YOUNG, JK MCKENZIE, JC BRADY, LS HERKENHAM, M AF YOUNG, JK MCKENZIE, JC BRADY, LS HERKENHAM, M TI HYPOTHALAMIC-LESIONS INCREASE LEVELS OF NEUROPEPTIDE-Y MESSENGER-RNA IN THE ARCUATE NUCLEUS OF MICE SO NEUROSCIENCE LETTERS LA English DT Article DE HYPOTHALAMUS; NEUROPEPTIDE Y; LESION; GOLDTHIOGLUCOSE; IN SITU HYBRIDIZATION; MESSENGER-RNA ID CEREBRAL GLUCOSE-UTILIZATION; MESSENGER-RIBONUCLEIC-ACID; FOOD-DEPRIVATION; RAT-BRAIN; EXPRESSION; NPY; IMMUNOREACTIVITY; GLUCOCORTICOIDS; LOCALIZATION; HYPERPHAGIA AB A recent study demonstrated that hypothalamic lesions induced by goldthioglucose (GTG) in mice produced an increase in neuronal immunoreactivity for neuropeptide Y (NPY) in the hypothalamic arcuate nucleus. Since NPY is a potent stimulator of feeding, this increase represented a potential explanation for the hyperphagia seen after GTG lesions. To examine whether or not this increase in NPY immunoreactivity was accompanied by an increase in the mRNA for NPY, in situ hybridization histochemistry for NPY mRNA in control and in lesioned mice was performed. A 47% increase in NPY mRNA levels in the arcuate nucleus was observed in lesioned mice compared with controls, suggesting that an increased expression of the gene for NPY contributes to elevations in hypothalamic NPY after lesioning. This elevation in NPY may, in turn, relate to mechanisms provoking hyperphagia. C1 NIMH, CLIN NEUROENDOCRINOL BRANCH, FUNCT NEUROANAT SECT, BETHESDA, MD 20892 USA. RP HOWARD UNIV, DEPT ANAT, 520 W ST NW, WASHINGTON, DC 20059 USA. OI Young, John/0000-0002-1294-942X NR 32 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 EI 1872-7972 J9 NEUROSCI LETT JI Neurosci. Lett. PD JAN 3 PY 1994 VL 165 IS 1-2 BP 13 EP 17 DI 10.1016/0304-3940(94)90698-X PG 5 WC Neurosciences SC Neurosciences & Neurology GA MU611 UT WOS:A1994MU61100004 PM 8015714 ER PT J AU KRSMANOVIC, LZ VIRMANI, MA STOJILKOVIC, SS CATT, KJ AF KRSMANOVIC, LZ VIRMANI, MA STOJILKOVIC, SS CATT, KJ TI STIMULATION OF GONADOTROPIN-RELEASING-HORMONE SECRETION BY ACETYL-L-CARNITINE IN HYPOTHALAMIC NEURONS AND GT1 NEURONAL CELLS SO NEUROSCIENCE LETTERS LA English DT Article DE HYPOTHALAMUS; GONADOTROPIN-RELEASING HORMONE; GNRH NEURONS; PULSATILE SECRETION ID RECEPTORS; SYSTEM; RATS AB Pulsatile gonadotropin-releasing hormone (GnRH) secretion from perifused hypothalamic cells and GT1-1 neuronal cells was significantly increased after culture in medium containing 100 mu M acetyl-L-carnitine (ALC). This action of ALC was largely due to an increase in the spike amplitude of GnRH release. In addition, the receptor-mediated release of GnRH by N-methyl-D-aspartic acid and endothelin was significantly increased in perifused cells cultured in ALC-enriched medium. Stimulatory effects of ALC on basal, high K+- and agonist-induced GnRH release were also observed during long-term culture of primary hypothalamic neurons. Similar effects of ALC were evident in cultured GT1-1 cells and were accompanied by a significant increase in cell number. These observations in normal and transformed GnRH neurons demonstrate that ALC promotes the growth and secretory activity of neuropeptide-producing cells of the hypothalamus. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. SIGMA TAU PHARMACEUT CO,RES & DEV,I-00040 POMEZIA,ITALY. NR 26 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JAN 3 PY 1994 VL 165 IS 1-2 BP 33 EP 36 DI 10.1016/0304-3940(94)90702-1 PG 4 WC Neurosciences SC Neurosciences & Neurology GA MU611 UT WOS:A1994MU61100008 PM 8015733 ER PT J AU MELLEMGAARD, A ENGHOLM, G MCLAUGHLIN, JK OLSEN, JH AF MELLEMGAARD, A ENGHOLM, G MCLAUGHLIN, JK OLSEN, JH TI RISK-FACTORS FOR RENAL-CELL CARCINOMA IN DENMARK .3. ROLE OF WEIGHT, PHYSICAL-ACTIVITY AND REPRODUCTIVE FACTORS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article; Proceedings Paper CT UICC Meeting on Breast-Cancer Screening in Pre-menopausal Women in Developed Countries CY SEP 29-OCT 01, 1993 CL GENEVA, SWITZERLAND SP UNION INT CONTRE CANC ID CANCER; WOMEN; MORTALITY; OBESITY; MEN AB A population-based case-control study of risk factors for renal-cell carcinoma was conducted in Denmark from 1989 to 1992. A total of 368 histologically verified cases and 396 controls were included. Information on weight, height, physical activity and reproductive factors were collected in a structured interview, along with information on other suspected risk factors. A significant increase in risk was seen for obese women but not obese men. Although there was no clear gradient, the risk was highest among women with a relative weight in the upper 5% (OR 6.1; 95% Cl, 2.3 to 16.1). The increased risk was most evident for high relative weight in ages 30 to 50. No association was observed for height or physical activity. Use of amphetamines was associated with increased risk but, because of the close link with obesity, we were unable to provide evidence that amphetamines are an independent risk factor. We found some evidence for an association with reproductive variables, including decreased risk for women with late menarche and first pregnancy and birth. We observed no association with number of pregnancies or age at menopause, or use of estrogen-containing medication. (C) 1994 Wiley-Liss, Inc. C1 NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. RP MELLEMGAARD, A (reprint author), DANISH CANC SOC,INST CANC EPIDEMIOL,DANISH CANC REGISTRY,BOX 839,DK-2100 COPENHAGEN,DENMARK. NR 22 TC 66 Z9 68 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 2 PY 1994 VL 56 IS 1 BP 66 EP 71 PG 6 WC Oncology SC Oncology GA MP711 UT WOS:A1994MP71100012 PM 8262680 ER PT B AU LE, DX THOMA, GR WECHSLER, H AF LE, DX THOMA, GR WECHSLER, H GP IEEE TI DOCUMENT CLASSIFICATION USING CONNECTIONIST MODELS SO 1994 IEEE INTERNATIONAL CONFERENCE ON NEURAL NETWORKS, VOL 1-7 LA English DT Proceedings Paper CT 1994 IEEE International Conference on Neural Networks (ICNN 94) - 1st IEEE World Congress on Computational Intelligence CY JUN 26-29, 1994 CL ORLANDO, FL SP IEEE, NEURAL NETWORKS COUNCIL, IEEE, ORLANDO SECT DE BACK PROPAGATION; DOCUMENT PROCESSING; PROBABILISTIC CONNECTIONIST; RADIAL BASIS FUNCTION; SELF-ORGANIZING FEATURE MAP; TEXTUAL CLASSIFICATION C1 NATL LIB MED,LISTER HILL NATL CTR BIOMED COMMUN,BETHESDA,MD 20894. NR 0 TC 1 Z9 1 U1 0 U2 0 PU I E E E PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 BN 0-7803-1901-X PY 1994 BP 3009 EP 3014 PG 6 WC Automation & Control Systems; Computer Science, Artificial Intelligence SC Automation & Control Systems; Computer Science GA BC54C UT WOS:A1994BC54C00561 ER PT B AU HAUSER, SE ROY, G THOMA, GR AF HAUSER, SE ROY, G THOMA, GR BE Campbell, DK Chen, M Ogawa, K TI OPTICAL DISK JUKEBOX PERFORMANCE IN MULTI-USER APPLICATIONS SO 1994 TOPICAL MEETING ON OPTICAL DATA STORAGE SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT 1994 Topical Meeting on Optical Data Storage CY MAY 16-18, 1994 CL DANA POINT, CA SP OPT SOC AMER, SOC PHOTO OPT INSTRUMENTAT ENGINEERS, IEEE LASERS & ELECTRO OPT SOC C1 NATL LIB MED,LISTER HILL NATL CTR BIOMED COMMUN,BETHESDA,MD 20894. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-1671-1 J9 P SOC PHOTO-OPT INS PY 1994 VL 2338 BP 87 EP 92 DI 10.1117/12.190169 PG 6 WC Optics SC Optics GA BB83T UT WOS:A1994BB83T00011 ER PT J AU MERCHENTHALER, I LIPOSITS, ZS AF MERCHENTHALER, I LIPOSITS, ZS TI MAPPING OF THYROTROPIN-RELEASING-HORMONE (TRH) NEURONAL SYSTEMS OF RAT FOREBRAIN PROJECTING TO THE MEDIAN-EMINENCE AND THE OVLT - IMMUNOCYTOCHEMISTRY COMBINED WITH RETROGRADE LABELING AT THE LIGHT AND ELECTRON-MICROSCOPIC LEVELS SO ACTA BIOLOGICA HUNGARICA LA English DT Article DE DOUBLE LABELING; FLUOROGOLD; HYPOPHYSIOTROPIC; MEDIAN EMINENCE; HYPOTHALAMUS; NEUROANATOMY ID HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; CENTRAL-NERVOUS-SYSTEM; LOCALIZATION; DELINEATION; SECRETION; PITUITARY; AREA AB The thyrotropin-releasing hormone (TRH)-containing neurons that project to portal capillaries of the external zone of the median eminence (ME) and fenestrated capillaries of the organum vasculosum of the lamina terminalis (OVLT) were identified on thin paraffin and thick vibratome sections using a combination of retrograde labeling with peripherally administered Fluoro-Gold and fluorescence immunocytochemistry. The results indicate that the vast majority of those TRH neurons that project to the ME and the OVLT is located in the paraventricular nucleus (PVN), and most abundantly, in its medial parvicellular subdivision. Although numerous TRH-immunoreactive (TRH-i) neurons are present in other hypothalamic areas of the brain, only a few of them in the dorsal hypothalamic area behind the PVN and the periventricular preoptic nucleus could be retrogradely labeled. Since only a few Fluoro-Gold-accumulating and TRH-i perikarya were seen in other nuclei than the PVN, it is likely that the majority of nerve terminals in the OVLT also originates from TRH-i perikarya in the PVN. Fluoro-Gold, an electron-dense substance, is stored in the lysosomes of hypophysiotropic TRH-i perikarya and thus, it provides an excellent model for electron microscopic characterization of hypophysiotropic neurons at both the light and electron microscopic levels. The data together provides additional morphological evidence for the key role of the PVN in the regulation of TSH secretion. C1 NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,FUNCTIONAL MORPHOL SECT,RES TRIANGLE PK,NC 27709. ALBERT SZENT GYORGYI MED UNIV,DEPT ANAT,SZEGED,HUNGARY. NR 28 TC 35 Z9 35 U1 0 U2 0 PU AKADEMIAI KIADO PI BUDAPEST PA PO BOX 245, H-1519 BUDAPEST, HUNGARY SN 0236-5383 J9 ACTA BIOL HUNG JI Acta Biol. Hung. PY 1994 VL 45 IS 2-4 BP 361 EP 374 PG 14 WC Biology SC Life Sciences & Biomedicine - Other Topics GA QF418 UT WOS:A1994QF41800019 PM 7725828 ER PT J AU DAOPIN, S DAVIES, DR SCHLUNEGGER, MP GRUTTER, MG AF DAOPIN, S DAVIES, DR SCHLUNEGGER, MP GRUTTER, MG TI COMPARISON OF 2 CRYSTAL-STRUCTURES OF TGF-BETA-2 - THE ACCURACY OF REFINED PROTEIN STRUCTURES SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID HUMAN TRANSFORMING GROWTH-FACTOR-BETA-2; ALCALIGENES-FAECALIS S-6; X-RAY; 3-DIMENSIONAL STRUCTURE; POPLAR PLASTOCYANIN; 1.8-A RESOLUTION; INTERLEUKIN-1-BETA AB Transforming growth factor-beta is a multifunctional cell-growth regulator and is a member of the TGF-beta superfamily of cytokines. Each monomer is 112 amino acids long and the mature active form is a 25 kDa homodimer. Recently, the crystal structure of TGF-beta 2 has been determined independently in two laboratories [Daopin, Piez, Ogawa and Davies (1992). Science, 257, 369-373; Schlunegger and Grutter (1992). Nature (London), 358, 430-434] and subsequently refined to higher resolutions [Daopin, Li and Davies (1993). Proteins Struct. Funct. Genet. In the press; Schlunegger and Grutter (1993). J. Mel. Biol. In the press]. A detailed structural comparison shows that the two structures are nearly identical with the differences mostly located on the mobile regions of the molecule. The r.m.s. differences between the two structures are 0.10 Angstrom for 104 pairs of C-alpha atoms, 0.15 Angstrom for 434 pairs of main-chain atoms, 0.33 Angstrom for 860 out of 890 pairs of protein atoms and a correlation of 90% between the temperature B factors of all protein atoms. Based on a comparison of the water molecules, a B value of 60.0 Angstrom(2) is recommended as the cut off for modeling new waters. The structural identity is striking because in one case the material was expressed in vivo in CHO cells whereas in the other case it was expressed in E. coli and had to be refolded in vitro. The overall coordinate errors are estimated to be 0.21 Angstrom from the Luzzati plot, 0.18 Angstrom from the sigma (A) plot, 0.24 Angstrom with Cruickshank's equations and 0.25 Angstrom using the empirical method of Ferry and Stroud. These estimates are comparable to the r.m.s. structure superposition. The r.m.s. differences correlate very well with the crystallographic B values and the relation is best described with the Cruickshank formula. In addition to the estimation of an overall error, a new application of the Cruickshank formula is presented here to estimate the local errors. (C) 1994 International Union of Crystallography C1 CIBA GEIGY AG,DEPT BIOTECHNOL,DIV PHARMACEUT,CH-4002 BASEL,SWITZERLAND. RP DAOPIN, S (reprint author), NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 30 TC 32 Z9 34 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD JAN 1 PY 1994 VL 50 BP 85 EP 92 DI 10.1107/S090744499300808X PN 1 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA MR637 UT WOS:A1994MR63700012 PM 15299480 ER PT J AU REILLY, JJ MAKI, R NARDOZZI, J SCHULKIN, J AF REILLY, JJ MAKI, R NARDOZZI, J SCHULKIN, J TI THE EFFECTS OF LESIONS OF THE BED NUCLEUS OF THE STRIA TERMINALIS ON SODIUM APPETITE SO ACTA NEUROBIOLOGIAE EXPERIMENTALIS LA English DT Note DE SODIUM APPETITE; MINERALOCORTICOIDS; BED NUCLEUS OF THE STRIA TERMINALIS ID MEDIAL AMYGDALA; ANGIOTENSIN-II; SALT APPETITE; RAT; ORGANIZATION; DAMAGE; SYSTEM; REGION; ALTER AB Lesions of the bed nucleus of the stria terminalis result in decrements in sodium ingestion. Specifically, sodium ingestion that is aroused by mineralocorticoids, in addition to sodium depletion, was reduced in rats with large lesions of the bed nucleus of the stria terminalis. Need-free salt ingestion was also reduced. These results suggest that the bed nucleus of the stria terminalis may be involved in the regulation of sodium appetite. C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. RP REILLY, JJ (reprint author), UNIV PENN,DEPT BIOL,PHILADELPHIA,PA 19104, USA. NR 25 TC 27 Z9 27 U1 0 U2 0 PU NENCKI INST EXPERIMENTAL BIOLOGY PI WARSAW PA UL PASTEURA 3, 02-093 WARSAW, POLAND SN 0065-1400 J9 ACTA NEUROBIOL EXP JI Acta Neurobiol. Exp. PY 1994 VL 54 IS 3 BP 253 EP 257 PG 5 WC Neurosciences SC Neurosciences & Neurology GA PJ029 UT WOS:A1994PJ02900007 PM 7817841 ER PT J AU JOHNSON, KA FORD, LG KRAMER, B GREENWALD, P AF JOHNSON, KA FORD, LG KRAMER, B GREENWALD, P TI OVERVIEW OF UNITED-STATES NATIONAL-CANCER-INSTITUTE (USNCI) CHEMOPREVENTION RESEARCH SO ACTA ONCOLOGICA LA English DT Article ID BREAST-CANCER; POSTMENOPAUSAL WOMEN; RANDOMIZED TRIAL; PROSTATE-CANCER; DIETARY FIBER; BETA-CAROTENE; RISK-FACTORS; TAMOXIFEN; HYPERPLASIA; EXPRESSION AB The National Cancer Institute's (NCI) chemoprevention plan employs a strategy of basic and epidemiologic studies, followed by a structured preclinical process to bring chemopreventive agents into clinical testing. The field of chemoprevention is progressing rapidly and has reached the point where a coordinated international approach for large-scale trials would be useful. At present, NCI is sponsoring nine large trials (over $1 million per year per trial); in addition, nine agents are in phase I or II clinical testing. A number of these agents should be ready soon for phase III testing. Resources required for large-scale trials compel greater attention to efficient trial designs, concept development and review, priority setting, management, budgeting, and collaboration. RP JOHNSON, KA (reprint author), NCI,DIV CANC PREVENT & CONTROL,ROOM 300,EPN,BETHESDA,MD 20892, USA. NR 45 TC 3 Z9 3 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0284-186X J9 ACTA ONCOL JI Acta Oncol. PY 1994 VL 33 IS 1 BP 5 EP 11 PG 7 WC Oncology SC Oncology GA ND588 UT WOS:A1994ND58800001 PM 8142125 ER PT J AU CHOU, SP AF CHOU, SP TI SEX-DIFFERENCES IN MORBIDITY AMONG RESPONDENTS CLASSIFIED AS ALCOHOL ABUSERS AND/OR DEPENDENT - RESULTS OF A NATIONAL SURVEY SO ADDICTION LA English DT Article ID WOMEN; DISEASE; HEALTH; MEN AB To date, none of the studies on gender differences in physical morbidity have focused on persons classified as DSM-III-R alcohol abusers and/or dependent in the general population. This Data Note presents data from a nationally representative survey on drinking practices and related problems for the purpose of examining gender differences in physical morbidity among respondents receiving these diagnoses. Results indicated that for certain major sociodemographic subgroups of the population, gender differences in morbidity were significant. The female-to-male adds ratios of these subgroups generally varied within the range of 1.5 and 2.0, reflecting about two times greater odds of experiencing morbid conditions for females when compared to males. RP CHOU, SP (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,5600 FISHERS LANE,ROOM 14C-26,ROCKVILLE,MD 20857, USA. NR 15 TC 4 Z9 5 U1 0 U2 0 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD JAN PY 1994 VL 89 IS 1 BP 87 EP 93 DI 10.1111/j.1360-0443.1994.tb00853.x PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA MT355 UT WOS:A1994MT35500017 PM 8148748 ER PT B AU Schuster, CR AF Schuster, CR BE Edwards, G Lader, M TI Ideological beliefs influence the feasibilities for policy change SO ADDICTION: PROCESSES OF CHANGE SE SOCIETY FOR THE STUDY OF ADDICTION MONOGRAPH LA English DT Proceedings Paper CT Meeting on Addiction - Processes of Change CY APR, 1992 CL CUMBERLAND LODGE, WINDSOR GREAT PARK, ENGLAND SP Soc Study Addict HO CUMBERLAND LODGE C1 NIDA,ADDICT RES CTR,ROCKVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIVERSITY PRESS PI OXFORD PA WALTON ST, OXFORD, ENGLAND OX2 6DP BN 0-19-262433-4 J9 SOC ST ADD MG PY 1994 IS 3 BP 203 EP 216 PG 14 WC Substance Abuse SC Substance Abuse GA BF38Q UT WOS:A1994BF38Q00011 ER PT J AU WINDLE, C AF WINDLE, C TI THE SHIFT TO RESEARCH SYNTHESIS SO ADMINISTRATION AND POLICY IN MENTAL HEALTH LA English DT Article ID META-ANALYSIS; METAANALYSIS RP WINDLE, C (reprint author), NIMH,DIV EPIDEMIOL & SERV RES,ROCKVILLE,MD 20857, USA. NR 10 TC 2 Z9 2 U1 0 U2 0 PU HUMAN SCI PRESS INC PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 SN 0894-587X J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD JAN PY 1994 VL 21 IS 3 BP 263 EP 267 DI 10.1007/BF00707492 PG 5 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA NC262 UT WOS:A1994NC26200010 ER PT J AU GOODNIGHT, J MISCHAK, H MUSHINSKI, JF AF GOODNIGHT, J MISCHAK, H MUSHINSKI, JF TI SELECTIVE INVOLVEMENT OF PROTEIN-KINASE-C ISOZYMES IN DIFFERENTIATION AND NEOPLASTIC TRANSFORMATION SO ADVANCES IN CANCER RESEARCH, VOL 64 SE ADVANCES IN CANCER RESEARCH LA English DT Review ID NERVE GROWTH-FACTOR; HUMAN NEURO-BLASTOMA; PHORBOL ESTER RECEPTOR; MURINE ERYTHROLEUKEMIA-CELLS; MOUSE EPIDERMAL-CELLS; PROMYELOCYTIC LEUKEMIA-CELLS; HUMAN NEUROBLASTOMA-CELLS; COLONY-STIMULATING FACTOR; HUMAN MONOCYTIC DIFFERENTIATION; SIGNAL TRANSDUCTION PATHWAYS RP GOODNIGHT, J (reprint author), NCI,GENET LAB,BETHESDA,MD 20892, USA. RI Mischak, Harald/E-8685-2011 NR 348 TC 113 Z9 113 U1 1 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0065-230X J9 ADV CANCER RES JI Adv.Cancer Res. PY 1994 VL 64 BP 159 EP 209 DI 10.1016/S0065-230X(08)60838-6 PG 51 WC Oncology SC Oncology GA BB94L UT WOS:A1994BB94L00006 PM 7879658 ER PT S AU SUTTON, SM EISNER, EJ BLOOM, DL BLOOM, PN AF SUTTON, SM EISNER, EJ BLOOM, DL BLOOM, PN BE Allen, CT John, DR TI THE MAMMOGRAPHY GUIDELINES CONTROVERSY - WHAT DO WOMEN THINK SO ADVANCES IN CONSUMER RESEARCH, VOL XXI SE ADVANCES IN CONSUMER RESEARCH LA English DT Article; Proceedings Paper CT 21st Annual Conference of the Association-for-Consumer-Research CY OCT 07-10, 1993 CL NASHVILLE, TN SP ASSOC CONSUMER RES AB Medical researchers have begun to question the appropriateness of guidelines (supported by the National Cancer Institute, American Cancer Society, and others) which recommend that women between forty and fifty obtain mammograms every one to two years. This paper reports on the early stages of a consumer research program which seeks to understand how women are responding to this controversy. The findings have implications both for dealing with the current controversy and for improving preventive health programs of all types. C1 UNIV N CAROLINA,CHAPEL HILL,NC 27599. RP SUTTON, SM (reprint author), NCI,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 1 U2 2 PU ASSOC CONSUMER RESEARCH PI PROVO PA GRAD SCHOOL MANAGEMENT, BRIGHAM YOUNG UNIV, PROVO, UT 84602 SN 0098-9258 BN 0-915552-32-9 J9 ADV CONSUM RES PY 1994 VL 21 BP 387 EP 391 PG 5 WC Business; Communication SC Business & Economics; Communication GA BA10V UT WOS:A1994BA10V00095 ER PT S AU FISCHER, PH BIRD, RE KASPRZYK, PG KING, CR TURNER, NA PASTAN, I KIHARA, A BATRA, J AF FISCHER, PH BIRD, RE KASPRZYK, PG KING, CR TURNER, NA PASTAN, I KIHARA, A BATRA, J BE Weber, G TI IN-VITRO AND IN-VIVO ACTIVITY OF A RECOMBINANT TOXIN, OLX-209, WHICH TARGETS THE ERBB-2 ONCOPROTEIN SO ADVANCES IN ENZYME REGULATION, VOL 34 SE ADVANCES IN ENZYME REGULATION LA English DT Article; Proceedings Paper CT 34TH Symposium on Regulation of Enzyme Activity and Synthesis in Normal and Neoplastic Tissues CY OCT 04-05, 1993 CL INDIANA UNIV SCH MED, INDIANAPOLIS, IN HO INDIANA UNIV SCH MED ID GROWTH-FACTOR-RECEPTOR; HUMAN-BREAST; PROTO-ONCOGENE; NEU ONCOGENE; AMPLIFICATION; CANCER; GENE; PROTOONCOGENE; C-ERBB-2; OVEREXPRESSION C1 NCI,BETHESDA,MD 20892. RP FISCHER, PH (reprint author), ONCOLOGIX INC,RES & DEV,GAITHERSBURG,MD 20878, USA. NR 21 TC 6 Z9 6 U1 1 U2 1 PU PERGAMON PRESS LTD PI OXFORD PA THE BOULEVARD LANGFORD LANE KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0065-2571 BN 0-08-042482-1 J9 ADV ENZYME REGUL PY 1994 VL 34 BP 119 EP 128 DI 10.1016/0065-2571(94)90012-4 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA69D UT WOS:A1994BA69D00008 PM 7942269 ER PT J AU SPRITZ, RA HEARING, VJ AF SPRITZ, RA HEARING, VJ TI GENETIC-DISORDERS OF PIGMENTATION SO ADVANCES IN HUMAN GENETICS, 22 SE ADVANCES IN HUMAN GENETICS LA English DT Review ID NEGATIVE OCULOCUTANEOUS ALBINISM; LINKED OCULAR ALBINISM; FACTOR RECEPTOR PROTOONCOGENE; TYROSINASE-RELATED PROTEIN; SYNDROME TYPE-I; C-KIT RECEPTOR; WAARDENBURG SYNDROME TYPE-1; ALTERED COPPER-METABOLISM; SINGLE BASE INSERTION; HUP2 PAIRED DOMAIN C1 UNIV WISCONSIN,DEPT PEDIAT,MADISON,WI 53706. NCI,CELL BIOL LAB,BETHESDA,MD 20892. RP SPRITZ, RA (reprint author), UNIV WISCONSIN,DEPT MED GENET,MADISON,WI 53706, USA. NR 209 TC 70 Z9 73 U1 0 U2 3 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0065-275X J9 ADV HUM GENET JI Adv.Hum.Genet. PY 1994 VL 22 BP 1 EP 45 PG 45 WC Genetics & Heredity SC Genetics & Heredity GA BC58T UT WOS:A1994BC58T00001 PM 7539206 ER PT J AU KELLEY, MJ JOHNSON, BE AF KELLEY, MJ JOHNSON, BE TI GENETIC MECHANISMS OF SOLID TUMOR ONCOGENESIS SO ADVANCES IN INTERNAL MEDICINE, VOL 39 SE ADVANCES IN INTERNAL MEDICINE LA English DT Review ID RENAL-CELL CARCINOMA; FAMILIAL ADENOMATOUS POLYPOSIS; HUMAN BREAST-CANCER; WILD-TYPE P53; HUMAN LUNG-CANCER; NONPOLYPOSIS COLORECTAL-CARCINOMA; HUMAN HEPATOCELLULAR CARCINOMAS; HUMAN PROSTATE CARCINOMA; GERM-LINE MUTATIONS; RETINOBLASTOMA GENE RP KELLEY, MJ (reprint author), USN,NATL NAVAL MED CTR,NCI,MED ONCOL BRANCH,LUNG CANC BIOL SECT,BETHESDA,MD, USA. OI Kelley, Michael/0000-0001-9523-6080 NR 149 TC 12 Z9 12 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146 SN 0065-2822 J9 ADV INTERNAL MED JI Adv.Intern.Med. PY 1994 VL 39 SI 19 BP 93 EP 122 PG 30 WC Medicine, General & Internal SC General & Internal Medicine GA BZ78M UT WOS:A1994BZ78M00004 PM 8140969 ER PT J AU QUINN, TC ZENILMAN, J ROMPALO, A AF QUINN, TC ZENILMAN, J ROMPALO, A TI SEXUALLY-TRANSMITTED DISEASES - ADVANCES IN DIAGNOSIS AND TREATMENT SO ADVANCES IN INTERNAL MEDICINE, VOL 39 SE ADVANCES IN INTERNAL MEDICINE LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; HERPES-SIMPLEX VIRUS; PELVIC INFLAMMATORY DISEASE; CHLAMYDIA-TRACHOMATIS INFECTION; RESISTANT NEISSERIA-GONORRHOEAE; HUMAN PAPILLOMAVIRUS INFECTION; GENITAL-TRACT INFECTION; HEPATITIS-C VIRUS; BACTERIAL VAGINOSIS; RISK-FACTORS C1 JOHNS HOPKINS UNIV,SCH MED,DIV INFECT DIS,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE CITY HLTH DEPT,SEXUALLY TRANSMITTED DIS CLIN,DIV INFECT DIS,BALTIMORE,MD. RP QUINN, TC (reprint author), NIAID,IMMUNOREGULAT LAB,BETHESDA,MD, USA. NR 228 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146 SN 0065-2822 J9 ADV INTERNAL MED JI Adv.Intern.Med. PY 1994 VL 39 SI 19 BP 149 EP 196 PG 48 WC Medicine, General & Internal SC General & Internal Medicine GA BZ78M UT WOS:A1994BZ78M00006 PM 8140954 ER PT J AU HOOFNAGLE, JH AF HOOFNAGLE, JH TI THERAPY OF ACUTE AND CHRONIC VIRAL-HEPATITIS SO ADVANCES IN INTERNAL MEDICINE, VOL 39 SE ADVANCES IN INTERNAL MEDICINE LA English DT Review ID RANDOMIZED CONTROLLED TRIAL; NON-B-HEPATITIS; RECOMBINANT ALPHA-INTERFERON; PLACEBO-CONTROLLED TRIAL; CHRONIC NON-A; CHRONIC ACTIVE HEPATITIS; ADENINE-ARABINOSIDE MONOPHOSPHATE; AUTOIMMUNE CHRONIC HEPATITIS; HUMAN-IMMUNODEFICIENCY-VIRUS; CHRONIC DELTA-HEPATITIS RP HOOFNAGLE, JH (reprint author), NIDDK,DIV DIGEST DIS & NUTR,BETHESDA,MD, USA. NR 151 TC 81 Z9 82 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146 SN 0065-2822 J9 ADV INTERNAL MED JI Adv.Intern.Med. PY 1994 VL 39 SI 19 BP 241 EP 275 PG 35 WC Medicine, General & Internal SC General & Internal Medicine GA BZ78M UT WOS:A1994BZ78M00008 PM 8140956 ER PT J AU HOFFMAN, GS FAUCI, AS AF HOFFMAN, GS FAUCI, AS TI EMERGING CONCEPTS IN THE MANAGEMENT OF VASCULITIC DISEASES SO ADVANCES IN INTERNAL MEDICINE, VOL 39 SE ADVANCES IN INTERNAL MEDICINE LA English DT Review ID INTRAVENOUS GAMMA-GLOBULIN; INTERLEUKIN-1 RECEPTOR ANTAGONIST; GIANT-CELL ARTERITIS; CHURG-STRAUSS ANGIITIS; WEGENERS GRANULOMATOSIS; POLYMYALGIA RHEUMATICA; BEHCETS-DISEASE; SYSTEMIC VASCULITIS; TEMPORAL ARTERITIS; POLYARTERITIS-NODOSA C1 CLEVELAND CLIN FDN,DEPT RHEUMAT & IMMUNOL DIS,CLEVELAND,OH 44195. RP HOFFMAN, GS (reprint author), NIAID,IMMUNOREGULAT LAB,VASCULITIS & RELATED DIS SECT,BLDG 10,BETHESDA,MD 20892, USA. NR 81 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146 SN 0065-2822 J9 ADV INTERNAL MED JI Adv.Intern.Med. PY 1994 VL 39 SI 19 BP 277 EP 303 PG 27 WC Medicine, General & Internal SC General & Internal Medicine GA BZ78M UT WOS:A1994BZ78M00009 PM 8140957 ER PT J AU SCHNITTMAN, SM FANCI, AS AF SCHNITTMAN, SM FANCI, AS TI HUMAN-IMMUNODEFICIENCY-VIRUS AND ACQUIRED-IMMUNODEFICIENCY-SYNDROME - AN UPDATE SO ADVANCES IN INTERNAL MEDICINE, VOL 39 SE ADVANCES IN INTERNAL MEDICINE LA English DT Review ID CD4+ T-CELLS; MULTIDRUG-RESISTANT TUBERCULOSIS; HIV-1 REVERSE-TRANSCRIPTASE; ENVELOPE GLYCOPROTEIN GP160; FOLLICULAR DENDRITIC CELLS; BLOOD MONONUCLEAR-CELLS; CYTOTOXIC LYMPHOCYTES-T; NECROSIS FACTOR-ALPHA; CONTROLLED TRIAL; CONFERS PROTECTION C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RP SCHNITTMAN, SM (reprint author), NIAID,DIV AIDS,MED BRANCH,BETHESDA,MD 20892, USA. NR 136 TC 61 Z9 62 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146 SN 0065-2822 J9 ADV INTERNAL MED JI Adv.Intern.Med. PY 1994 VL 39 SI 19 BP 305 EP 355 PG 51 WC Medicine, General & Internal SC General & Internal Medicine GA BZ78M UT WOS:A1994BZ78M00010 PM 8140958 ER PT B AU GANDJBAKHCHE, AH NOSSAL, R BONNER, RF AF GANDJBAKHCHE, AH NOSSAL, R BONNER, RF BE Alfano, RR Katzir, A TI THEORETICAL-STUDY OF RESOLUTION LIMITS FOR TIME-RESOLVED IMAGING OF HUMAN BREAST SO ADVANCES IN LASER AND LIGHT SPECTROSCOPY TO DIAGNOSE CANCER AND OTHER DISEASES SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Advances in Laser and Light Spectroscopy to Diagnose Cancer and Other Diseases CY JAN 23-24, 1994 CL LOS ANGELES, CA SP SOC PHOTO OPT INSTRUMENTAT ENGINEERS C1 NIH,BETHESDA,MD 20892. RI Bonner, Robert/C-6783-2015 NR 0 TC 10 Z9 10 U1 0 U2 0 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-1430-1 J9 P SOC PHOTO-OPT INS PY 1994 VL 2135 BP 176 EP 185 DI 10.1117/12.175992 PG 10 WC Oncology; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BA44F UT WOS:A1994BA44F00019 ER PT B AU KNUTTEL, A SCHMITT, JM SHAY, M KNUTSON, JR AF KNUTTEL, A SCHMITT, JM SHAY, M KNUTSON, JR BE Alfano, RR Katzir, A TI STATIONARY LOW-COHERENCE LIGHT IMAGING AND SPECTROSCOPY USING A CCD CAMERA SO ADVANCES IN LASER AND LIGHT SPECTROSCOPY TO DIAGNOSE CANCER AND OTHER DISEASES SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Advances in Laser and Light Spectroscopy to Diagnose Cancer and Other Diseases CY JAN 23-24, 1994 CL LOS ANGELES, CA SP SOC PHOTO OPT INSTRUMENTAT ENGINEERS C1 NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPIE - INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA PO BOX 10, BELLINGHAM, WA 98227-0010 BN 0-8194-1430-1 J9 P SOC PHOTO-OPT INS PY 1994 VL 2135 BP 239 EP 250 PG 12 WC Oncology; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BA44F UT WOS:A1994BA44F00025 ER PT J AU EIDEN, L AF EIDEN, L TI NEUROAIDS - FOREWORD SO ADVANCES IN NEUROIMMUNOLOGY LA English DT Editorial Material RP EIDEN, L (reprint author), NIMH,CELL BIOL LAB,MOLEC NEUROSCI SECT,BLDG 36,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-5428 J9 ADV NEUROIMMUNOL JI Adv. Neuroimmunol. PY 1994 VL 4 IS 3 BP 145 EP 148 DI 10.1016/S0960-5428(06)80250-0 PG 4 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA PP109 UT WOS:A1994PP10900001 ER PT J AU BLACK, R SAGER, P AF BLACK, R SAGER, P TI SUMMARY OF WORKSHOP CONTRIBUTIONS SO ADVANCES IN NEUROIMMUNOLOGY LA English DT Editorial Material RP BLACK, R (reprint author), NIAID,6003 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-5428 J9 ADV NEUROIMMUNOL JI Adv. Neuroimmunol. PY 1994 VL 4 IS 3 BP 149 EP 156 DI 10.1016/S0960-5428(06)80251-2 PG 8 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA PP109 UT WOS:A1994PP10900002 PM 7874382 ER PT J AU BRENNEMAN, DE MCCUNE, SK MERVIS, RF HILL, JM AF BRENNEMAN, DE MCCUNE, SK MERVIS, RF HILL, JM TI GP120 AS AN ETIOLOGIC AGENT FOR NEUROAIDS - NEUROTOXICITY AND MODEL SYSTEMS SO ADVANCES IN NEUROIMMUNOLOGY LA English DT Article; Proceedings Paper CT 3rd Workshop on Neuro-AIDS CY AUG 16-19, 1993 CL PORTLAND, ME SP NIAID, DIV AIDS ID HUMAN-IMMUNODEFICIENCY-VIRUS; VASOACTIVE-INTESTINAL-PEPTIDE; NEURONAL CELL-DEATH; ENVELOPE PROTEIN; RECEPTOR-BINDING; PERIPHERAL-BLOOD; FRONTAL-CORTEX; HIV-INFECTION; T-CELL; BRAIN AB The search for an agent that can mediate the symptoms of NeuroAIDS has been directed at gp120, the major envelope protein from HIV. The toxicity associated with gp120 was examined asa model and predictor of the neuropathological and neuropsychiatric manifestations of AIDS. Studies of the neurotoxic effects of purified gp120 on neurons from the rodent CNS cell cultures indicated the following: potent and selective killing of subpopulations of hippocampal neurons; varying potency of gp120s obtained from various HIV isolates; complete and potent protection from gp120 killing action after treatment with peptides related to vasoactive intestinal peptide; and obligatory presence of glia for gp120-related toxicity. Investigations of gp120 treatment of rodents revealed: cortical neurodystrophy with reduced arborizations and swollen processes; delays in developmental behaviors involving motor skills; peptide T prevention or attenuation of the morphological and behavioral deficits/delays produced by administration of gp120; and impairment of learning in the Morris swim maze. In addition, studies of subcutaneously administered, radiolabeled gp120 in neonatal animals demonstrated the presence of toxic fragments of gp120 in the developing brain. With the use of model test systems of nonhuman derived cell cultures and neonatal rats, we have captured and predicted a number of the morphological and behavioral deficits associated with AIDS. These multidisciplinary studies of the actions of gp120 and associated fragments in rodents and rodent cells predict that the loss of cognitive and neurological function in patients with AIDS are attributed in part to interference of critical brain functions by the envelope protein, gp120. C1 NEUROMETRIX RES INC,COLUMBUS,OH 43212. CHILDRENS NATL MED CTR,DEPT NEONATOL,WASHINGTON,DC 20010. RP BRENNEMAN, DE (reprint author), NICHHD,LDN,SDMP,BLDG 49,RM 5A38,BETHESDA,MD 20892, USA. RI Mervis, Ronald/J-8952-2012 OI Mervis, Ronald/0000-0002-7503-7559 NR 35 TC 39 Z9 39 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-5428 J9 ADV NEUROIMMUNOL JI Adv. Neuroimmunol. PY 1994 VL 4 IS 3 BP 157 EP 165 DI 10.1016/S0960-5428(06)80252-4 PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA PP109 UT WOS:A1994PP10900003 PM 7874383 ER PT J AU BROUWERS, P DECARLI, C TUDORWILLIAMS, G CIVITELLO, L MOSS, H PIZZO, P AF BROUWERS, P DECARLI, C TUDORWILLIAMS, G CIVITELLO, L MOSS, H PIZZO, P TI INTERRELATIONS AMONG PATTERNS OF CHANGE IN NEUROCOGNITIVE, CT BRAIN IMAGING AND CD4 MEASURES ASSOCIATED WITH ANTIRETROVIRAL THERAPY IN CHILDREN WITH SYMPTOMATIC HIV-INFECTION SO ADVANCES IN NEUROIMMUNOLOGY LA English DT Article; Proceedings Paper CT 3rd Workshop on Neuro-AIDS CY AUG 16-19, 1993 CL PORTLAND, ME SP NIAID, DIV AIDS ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFUSION ZIDOVUDINE THERAPY; PEDIATRIC AIDS; BASAL GANGLIA; DIDEOXYINOSINE; ENCEPHALOPATHY; CALCIFICATION; INFANTS AB The interrelationships of patterns of change and variability between baseline and after 6 months of anti-retroviral therapy in neurocognitive, brain imaging, and immune measures were studied in 77 children with symptomatic HIV disease. Overall improvement in CNS structure/function after 6 months of anti-retroviral therapy was limited; new intracerebral calcifications tended to occur and old ones tended to progress in young children with vertically acquired HIV infection, despite treatment. Substantial inter-individual differences in change were however observed. Factors which explained part of the variance in the magnitude and direction of change were baseline structural and functional abnormalities, rating of degree of CNS penetration of the drug protocol, and concurrent changes on other variables. These preliminary data suggest that CNS specific effects of therapies as well as pretreatment status of CNS function/structure need to be taken into consideration when evaluating future trials of anti-retroviral therapy for children with symptomatic HIV infection. C1 NINCDS,EPILEPSY RES BRANCH,BETHESDA,MD 20892. CHILDRENS NATL MED CTR,WASHINGTON,DC 20070. RP BROUWERS, P (reprint author), NCI,CTR CLIN,PEDIAT BRANCH,RM 13N240,BETHESDA,MD 20892, USA. RI DeCarli, Charles/B-5541-2009 NR 29 TC 30 Z9 31 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-5428 J9 ADV NEUROIMMUNOL JI Adv. Neuroimmunol. PY 1994 VL 4 IS 3 BP 223 EP 231 DI 10.1016/S0960-5428(06)80260-3 PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA PP109 UT WOS:A1994PP10900011 PM 7874390 ER PT J AU RAUSCH, DM HEYES, M EIDEN, LE AF RAUSCH, DM HEYES, M EIDEN, LE TI EFFECTS OF CHRONIC ZIDOVUDINE ADMINISTRATION ON CNS FUNCTION AND VIRUS BURDEN AFTER PERINATAL SIV INFECTION IN RHESUS-MONKEYS SO ADVANCES IN NEUROIMMUNOLOGY LA English DT Article; Proceedings Paper CT 3rd Workshop on Neuro-AIDS CY AUG 16-19, 1993 CL PORTLAND, ME SP NIAID, DIV AIDS ID QUINOLINIC ACID AB Continuous intravenous administration of zidovudine (AZT) has been reported to improve cognitive function in HIV-infected pediatric patients (Pizzo et al., 1988). The effects of long-term zidovudine treatment in the perinatally infected pediatric population, including antiviral efficacy and effects on cognitive and motor function has not been systematically examined. These questions were addressed in rhesus macaque infants infected at birth with SIVSMM/B670, a primate model for infantile HIV infection and disease (Eiden et al., 1993a). Continuous or intermittent administration of AZT during the first 6 months following infection resulted in about a doubling of lifespan, a delay in the occurrence of motor impairment, and lower virus burden and quinolinic acid levels in cerebrospinal fluid (CSF) following administration of the antiviral drug. C1 NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,BETHESDA,MD 20892. RP RAUSCH, DM (reprint author), NIMH,CELL BIOL LAB,MOLEC NEUROSCI SECT,BLDG 36,BETHESDA,MD 20892, USA. OI Eiden, Lee/0000-0001-7524-944X NR 12 TC 7 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-5428 J9 ADV NEUROIMMUNOL JI Adv. Neuroimmunol. PY 1994 VL 4 IS 3 BP 233 EP 237 DI 10.1016/S0960-5428(06)80261-5 PG 5 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA PP109 UT WOS:A1994PP10900012 PM 7874391 ER PT J AU DACUNHA, A EIDEN, LE RAUSCH, DM AF DACUNHA, A EIDEN, LE RAUSCH, DM TI NEURONAL SUBSTRATES FOR SIV ENCEPHALOPATHY SO ADVANCES IN NEUROIMMUNOLOGY LA English DT Article; Proceedings Paper CT 3rd Workshop on Neuro-AIDS CY AUG 16-19, 1993 CL PORTLAND, ME SP NIAID, DIV AIDS ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; PREPROSOMATOSTATIN MESSENGER-RNA; QUINOLINIC ACID; RHESUS-MONKEYS; PREFRONTAL CORTEX; CEREBRAL-CORTEX; FRONTAL-CORTEX; AIDS BRAINS; SOMATOSTATIN; EXPRESSION RP DACUNHA, A (reprint author), NIMH,CELL BIOL LAB,MOLEC NEUROSCI SECT,BLDG 36,BETHESDA,MD 20892, USA. OI Eiden, Lee/0000-0001-7524-944X NR 33 TC 7 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-5428 J9 ADV NEUROIMMUNOL JI Adv. Neuroimmunol. PY 1994 VL 4 IS 3 BP 265 EP 271 DI 10.1016/S0960-5428(06)80266-4 PG 7 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA PP109 UT WOS:A1994PP10900017 PM 7874394 ER PT J AU CONANT, K TORNATORE, C ATWOOD, W MEYERS, K TRAUB, R MAJOR, EO AF CONANT, K TORNATORE, C ATWOOD, W MEYERS, K TRAUB, R MAJOR, EO TI IN-VIVO AND IN-VITRO INFECTION OF THE ASTROCYTE BY HIV-1 SO ADVANCES IN NEUROIMMUNOLOGY LA English DT Article; Proceedings Paper CT 3rd Workshop on Neuro-AIDS CY AUG 16-19, 1993 CL PORTLAND, ME SP NIAID, DIV AIDS ID HUMAN-IMMUNODEFICIENCY-VIRUS; CELLULAR-LOCALIZATION; BRAIN-TISSUE; GLIAL-CELLS; AIDS; ENCEPHALOPATHY; CHILDREN RP CONANT, K (reprint author), NIH,MOLEC MED & NEUROSCI LAB,BETHESDA,MD 20892, USA. NR 17 TC 32 Z9 33 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-5428 J9 ADV NEUROIMMUNOL JI Adv. Neuroimmunol. PY 1994 VL 4 IS 3 BP 287 EP 289 DI 10.1016/S0960-5428(06)80269-X PG 3 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA PP109 UT WOS:A1994PP10900020 PM 7874397 ER PT S AU NAGINENI, CN DETRICK, B HOOKS, JJ AF NAGINENI, CN DETRICK, B HOOKS, JJ BE Nussenblatt, RB Whitcup, SM Caspi, RR Gery, I TI HUMAN RETINAL PIGMENT EPITHELIAL CELLS SECRETE CYTOKINES IN RESPONSE TO INFLAMMATORY MEDIATORS SO ADVANCES IN OCULAR IMMUNOLOGY SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 6th International Symposium on the Immunology and Immunopathology of the Eye (IIPE) CY JUN 22-24, 1994 CL NIH CAMPUS, BETHESDA, MD HO NIH CAMPUS C1 NEI,IMMUNOL LAB,IMMUNOL & VIROL SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-81742-5 J9 INT CONGR SER PY 1994 VL 1068 BP 17 EP 20 PG 4 WC Immunology; Ophthalmology SC Immunology; Ophthalmology GA BC27A UT WOS:A1994BC27A00004 ER PT S AU ISHIMOTO, S CHANAUD, NP KOZHICH, AT FUKUSHIMA, A GERY, I WHITCUP, SM AF ISHIMOTO, S CHANAUD, NP KOZHICH, AT FUKUSHIMA, A GERY, I WHITCUP, SM BE Nussenblatt, RB Whitcup, SM Caspi, RR Gery, I TI ANTIBODIES AGAINST CELL ADHESION MOLECULES INHIBIT PROLIFERATION OF UVEITOGENIC LYMPHOCYTES INVITRO SO ADVANCES IN OCULAR IMMUNOLOGY SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 6th International Symposium on the Immunology and Immunopathology of the Eye (IIPE) CY JUN 22-24, 1994 CL NIH CAMPUS, BETHESDA, MD HO NIH CAMPUS C1 NEI,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-81742-5 J9 INT CONGR SER PY 1994 VL 1068 BP 39 EP 42 PG 4 WC Immunology; Ophthalmology SC Immunology; Ophthalmology GA BC27A UT WOS:A1994BC27A00010 ER PT S AU CASPI, RR AF CASPI, RR BE Nussenblatt, RB Whitcup, SM Caspi, RR Gery, I TI TH1 AND TH2 LYMPHOCYTES IN EXPERIMENTAL AUTOIMMUNE UVEORETINITIS SO ADVANCES IN OCULAR IMMUNOLOGY SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 6th International Symposium on the Immunology and Immunopathology of the Eye (IIPE) CY JUN 22-24, 1994 CL NIH CAMPUS, BETHESDA, MD HO NIH CAMPUS C1 NEI,BETHESDA,MD 20892. NR 0 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-81742-5 J9 INT CONGR SER PY 1994 VL 1068 BP 55 EP 58 PG 4 WC Immunology; Ophthalmology SC Immunology; Ophthalmology GA BC27A UT WOS:A1994BC27A00014 ER PT S AU FUKUSHIMA, A LAI, JC SHILOACH, J WHITCUP, SM GERY, I NUSSENBLATT, RB AF FUKUSHIMA, A LAI, JC SHILOACH, J WHITCUP, SM GERY, I NUSSENBLATT, RB BE Nussenblatt, RB Whitcup, SM Caspi, RR Gery, I TI DIVERSE LYMPHOCYTE RESPONSES TO DETERMINANTS OF HUMAN S-ANTIGEN (HS-AG) IN UVEITIC MONKEYS AND NORMAL HUMANS INDICATE A LACK OF SHARED IMMUNODOMINANT EPITOPES SO ADVANCES IN OCULAR IMMUNOLOGY SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 6th International Symposium on the Immunology and Immunopathology of the Eye (IIPE) CY JUN 22-24, 1994 CL NIH CAMPUS, BETHESDA, MD HO NIH CAMPUS C1 NEI,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-81742-5 J9 INT CONGR SER PY 1994 VL 1068 BP 63 EP 66 PG 4 WC Immunology; Ophthalmology SC Immunology; Ophthalmology GA BC27A UT WOS:A1994BC27A00016 ER PT S AU CHAN, CC DASTGHEIB, K HIKITA, N WALTON, RC NUSSENBLATT, RB BROEKHUYSE, RM AF CHAN, CC DASTGHEIB, K HIKITA, N WALTON, RC NUSSENBLATT, RB BROEKHUYSE, RM BE Nussenblatt, RB Whitcup, SM Caspi, RR Gery, I TI EXPERIMENTAL MELANIN-PROTEIN INDUCED UVEITIS (EMIU, FORMERLY EAAU) - IMMUNOPATHOLOGY, SUSCEPTIBILITY AND THERAPY SO ADVANCES IN OCULAR IMMUNOLOGY SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 6th International Symposium on the Immunology and Immunopathology of the Eye (IIPE) CY JUN 22-24, 1994 CL NIH CAMPUS, BETHESDA, MD HO NIH CAMPUS C1 NEI,IMMUNOL LAB,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-81742-5 J9 INT CONGR SER PY 1994 VL 1068 BP 91 EP 94 PG 4 WC Immunology; Ophthalmology SC Immunology; Ophthalmology GA BC27A UT WOS:A1994BC27A00023 ER PT S AU LI, Q DASTGHEIB, K LUYO, D EGWUAGU, C NUSSENBLATT, RB CHAN, CC AF LI, Q DASTGHEIB, K LUYO, D EGWUAGU, C NUSSENBLATT, RB CHAN, CC BE Nussenblatt, RB Whitcup, SM Caspi, RR Gery, I TI EXPRESSION OF TRANSFORMING GROWTH FACTOR-beta 1 (TGF beta 1) IN EXPERIMENTAL MELANIN PROTEIN INDUCED UVEITIS AND EXPERIMENTAL AUTOIMMUNE UVEITIS SO ADVANCES IN OCULAR IMMUNOLOGY SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 6th International Symposium on the Immunology and Immunopathology of the Eye (IIPE) CY JUN 22-24, 1994 CL NIH CAMPUS, BETHESDA, MD HO NIH CAMPUS C1 NEI,IMMUNOL LAB,BETHESDA,MD. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-81742-5 J9 INT CONGR SER PY 1994 VL 1068 BP 99 EP 102 PG 4 WC Immunology; Ophthalmology SC Immunology; Ophthalmology GA BC27A UT WOS:A1994BC27A00025 ER EF