FN Thomson Reuters Web of Science™ VR 1.0 PT J AU LEEHUANG, S HUANG, PL HUANG, PL BOURINBAIAR, AS CHEN, HC KUNG, HF AF LEEHUANG, S HUANG, PL HUANG, PL BOURINBAIAR, AS CHEN, HC KUNG, HF TI INHIBITION OF THE INTEGRASE OF HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) TYPE-1 BY ANTI-HIV PLANT-PROTEINS MAP30 AND GAP31 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE AIDS; ANTIVIRAL TARGET; DNA INTEGRATION; ANTIVIRAL AGENTS ID DNA INTEGRATION; RETROVIRAL INTEGRATION; ESCHERICHIA-COLI; INVITRO; CLEAVAGE; SEQUENCE; IDENTIFICATION; MECHANISM; HAIRPINS; PRODUCT AB MAP30 (Momordica anti-HIV protein of 30 kDa) and GAP31 (Gelonium anti-HIV protein of 31 kDa) are anti-HIV plant proteins that we have identified, purified, and cloned from the medicinal plants Momordica charantia and Gelonium multiflorum. These antiviral agents are capable of inhibiting infection of HIV type 1 (HIV-1) in T lymphocytes and monocytes as well as replication of the virus in already-infected cells, They are not toxic to normal uninfected cells because they are unable to enter healthy cells, MAP30 and GAP31 also possess an N-glycosidase activity on 28S ribosomal RNA and a topological activity on plasmid and viral DNAs including HIV-1 long terminal repeats (LTRs), LTRs are essential sites for integration of viral DNA into the host genome by viral integrase, We therefore investigated the effect of MAP30 and GAP31 on HIV-1 integrase, We report that both of these antiviral agents exhibit dose-dependent inhibition of HIV-1 integrase, Inhibition was observed in all of the three specific reactions catalyzed by the integrase, namely, 3' processing (specific cleavage of the dinucleotide GT from the viral substrate), strand transfer (integration), and ''disintegration'' (the reversal of strand transfer), Inhibition was studied by using oligonucleotide substrates with sequences corresponding to the U3 and U5 regions of HIV LTR, In the presence of 20 ng of viral substrate, 50 ng of target substrate, and 4 mu M integrase, total inhibition was achieved at equimolar concentrations of the integrase and the antiviral proteins, with EC(50) values of about 1 mu M. Integration of viral DNA into the host chromosome is a vital step in the replicative cycle of retroviruses, including the AIDS virus, The inhibition of HIV-1 integrase by MAP30 and GAP31 suggests that impediment of viral DNA integration may play a key role in the anti-HIV activity of these plant proteins. C1 AMER BIOSCI, NEW YORK, NY 10021 USA. NICHHD, BETHESDA, MD 20892 USA. NCI, FREDERICK CANC RES & DEV CTR, DIV CANC TREATMENT, BIOL RESPONSE MODIFIERS PROGRAM, FREDERICK, MD 21701 USA. RP LEEHUANG, S (reprint author), NYU, SCH MED, DEPT BIOCHEM, 550 1ST AVE, NEW YORK, NY 10016 USA. FU NIAID NIH HHS [R01 AI 31334] NR 38 TC 112 Z9 131 U1 2 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 12 PY 1995 VL 92 IS 19 BP 8818 EP 8822 DI 10.1073/pnas.92.19.8818 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RU759 UT WOS:A1995RU75900058 PM 7568024 ER PT J AU LIU, XW ROBINSON, GW GOUILLEUX, F GRONER, B HENNIGHAUSEN, L AF LIU, XW ROBINSON, GW GOUILLEUX, F GRONER, B HENNIGHAUSEN, L TI CLONING AND EXPRESSION OF STAT5 AND AN ADDITIONAL HOMOLOG (STAT5B) INVOLVED IN PROLACTIN SIGNAL-TRANSDUCTION IN MOUSE MAMMARY TISSUE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE JANUS KINASE; SIGNAL TRANSDUCERS AND ACTIVATORS OF TRANSCRIPTION; MAMMARY GLAND FACTOR; MILK PROTEIN ID PROTEIN GENE PROMOTER; TRANSGENIC MICE; GLAND AB Prolactin (PRL) induces transcriptional activation of milk protein genes, such as the whey acidic protein (WAP), beta-casein, and beta-lactoglobulin genes, through a signaling cascade encompassing the Janus kinase Jak2 and the mammary gland factor (MGF; also called Stat5), which belongs to the family of proteins of signal transducers and activators of transcription (STAT), We isolated and sequenced from mouse mammary tissue Stat5 mRNA and a previously unreported member, which we named Stat5b (Stat5 is renamed to Stat5a), On the protein level Stat5a and Stat5b show a 96% sequence similarity, The 5' and 3' untranslated regions of the two mRNAs are not conserved, Stat5a comprises 793 amino acids and is encoded by a mRNA of 4.2 kb, The Stat5b mRNA has a size of 5.6 kb and encodes a protein of 786 amino acids, Both Stat5a and Stat5b recognized the GAS site (gamma-interferon-activating sequence; TTCNNNGAA) in vitro and mediated PRL-induced transcription in COS cells transfected with a PRL receptor, Stat5b also induced basal transcription in the absence of PRL, Similar levels of Stat5a and Stat5b mRNAs were found in most tissues of virgin and lactating mice, but a differential accumulation of the Stat5 mRNAs was found in muscle and mammary tissue, The two RNAs are present in mammary tissue of immature virgin mice, and their levels increase up to day 16 of pregnancy, followed by a decline during lactation, The increase of Stat5 expression during pregnancy coincides with the activation of the WAP gene. C1 TUMOR BIOL CTR,INST EXPTL CANC RES,D-79106 FREIBURG,GERMANY. RP LIU, XW (reprint author), NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892, USA. RI Robinson, Gertraud/I-2136-2012 NR 26 TC 391 Z9 396 U1 0 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 12 PY 1995 VL 92 IS 19 BP 8831 EP 8835 DI 10.1073/pnas.92.19.8831 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RU759 UT WOS:A1995RU75900061 PM 7568026 ER PT J AU POMMIER, Y KOHLHAGEN, G KOHN, KW LETEURTRE, F WANI, MC WALL, ME AF POMMIER, Y KOHLHAGEN, G KOHN, KW LETEURTRE, F WANI, MC WALL, ME TI INTERACTION OF AN ALKYLATING CAMPTOTHECIN DERIVATIVE WITH A DNA-BASE AT TOPOISOMERASE I-DNA CLEAVAGE SITES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EUKARYOTIC TOPOISOMERASE; SEQUENCE REQUIREMENTS; ANTITUMOR-ACTIVITY; INHIBITION; BINDING; ABSENCE; ANALOGS; COMPLEX; BREAKS AB DNA topoisomerase I (top1) is a ubiquitous nuclear enzyme, It is specifically inhibited by camptothecin, a natural product derived from the bark of the tree Camptotheca acuminata. Camptothecin and several of its derivatives are presently in clinical trial and exhibit remarkable anticancer activity, The present study is a further investigation of the molecular interactions between the drug and the enzyme-DNA complex, We utilized an alkylating camptothecin derivative, 7-chloromethyl-10,11-methylenedioxycamptothecin (7-CIMe-MDO-CPT), and compared its activity against calf thymus top1 in a DNA oligonucleotide containing a single top1 cleavage site with the activity of its nonalkylating analog, 7-ethyl-10,11-methylenedioxycamptothecin (7-Et-MDO-CPT), In the presence of top1, 7-CIMe-MDO-CPT produced a DNA fragment that migrated more slowly than the top1-cleaved DNA fragment observed with 7-Et-MDO-CPT, Top1 was unable to religate this fragment in the presence of high NaCl concentration or proteinase K at 50 degrees C, This fragment was resistant to piperidine treatment and was also formed with an oligonucleotide containing a 7-deazaguanine at the 5' terminus of the top1-cleaved DNA (base +1), It was however cleaved by formic acid treatment followed by piperidine. These observations are consistent with alkylation of the +1 base (adenine or guanine) by 7-CIMe-MDO-CPT in the presence of top1 covalent complexes and provide direct evidence,that camptothecins inhibit top1 by binding at the enzyme-DNA interface. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP POMMIER, Y (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BLDG 37,ROOM 5C25,BETHESDA,MD 20892, USA. NR 37 TC 129 Z9 132 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 12 PY 1995 VL 92 IS 19 BP 8861 EP 8865 DI 10.1073/pnas.92.19.8861 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RU759 UT WOS:A1995RU75900067 PM 7568032 ER PT J AU LIPSKA, BK WEINBERGER, DR AF LIPSKA, BK WEINBERGER, DR TI GENETIC-VARIATION IN VULNERABILITY TO THE BEHAVIORAL-EFFECTS OF NEONATAL HIPPOCAMPAL DAMAGE IN RATS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE STRAIN SPECIFICITY; FISCHER 344 RATS; LEWIS RATS; MESOLIMBIC DOPAMINE SYSTEM; ANIMAL MODEL ID CORTICOTROPIN-RELEASING HORMONE; SUSCEPTIBLE LEWIS RATS; MESOLIMBIC DOPAMINE SYSTEM; NUCLEUS-ACCUMBENS; ADRENAL AXIS; STRAIN DIFFERENCES; INDUCED ARTHRITIS; CHRONIC MORPHINE; SPRAGUE-DAWLEY; STRESS AB We explored how two independent variables, one genetic (i.e., specific rat strains) and another environmental (i.e., a developmental excitotoxic hippocampal Lesion), contribute to phenotypic variation, Sprague-Dawley (SD), Fischer 344 (F344), and Lewis rats underwent two grades of neonatal excitotoxic damage: small and large ventral hippocampal (SVH and LVH) lesions, Locomotion was tested before puberty [postnatal day 35 (P35)] and after puberty (P56) following exposure to a novel environment or administration of amphetamine, The behavioral effects mere strain-and lesion-specific. As shown previously, SD rats with LVH lesions displayed enhanced spontaneous and amphetamine-induced locomotion as compared with controls at P56, but not at P35. SVH lesions in SD rats had no effect at any age, In F344 rats with LVH lesions, enhanced spontaneous and amphetamine-induced locomotion appeared early (P35) and was exaggerated at P56, SVH lesions in F344 rats resulted in a pattern of effects analogous to LVH lesions in SD rats-i.e., postpubertal onset of hyperlocomotion (P56), In Lewis rats, LVH lesions had no significant effect on novelty- or amphetamine-induced locomotion at any age, These data show that the degree of genetic predisposition and the extent of early induced hippocampal defect contribute to the particular pattern of behavioral outcome, These results may have implications for modeling interactions of genetic and environmental factors involved in schizophrenia, a disorder characterized by phenotypic heterogeneity, genetic predisposition, a developmental hippocampal abnormality, and vulnerability to environmental stress. RP LIPSKA, BK (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032, USA. RI Lipska, Barbara/E-4569-2017 NR 40 TC 108 Z9 109 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 12 PY 1995 VL 92 IS 19 BP 8906 EP 8910 DI 10.1073/pnas.92.19.8906 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RU759 UT WOS:A1995RU75900076 PM 7568041 ER PT J AU SAGA, T NEUMANN, RD HEYA, T SATO, J KINUYA, S LE, N PAIK, CH WEINSTEIN, JN AF SAGA, T NEUMANN, RD HEYA, T SATO, J KINUYA, S LE, N PAIK, CH WEINSTEIN, JN TI TARGETING CANCER MICROMETASTASES WITH MONOCLONAL-ANTIBODIES - A BINDING-SITE BARRIER SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PHARMACOLOGY; METASTASIS; IMMUNOTHERAPY ID HUMAN-MALIGNANT MELANOMA; SOLID TUMORS; INTERSTITIAL PRESSURE; SPATIAL-DISTRIBUTION; MODELING ANALYSIS; HUMAN-COLON; MACROMOLECULES; LOCALIZATION; XENOGRAFTS; ANTIGEN AB Monoclonal antibodies penetrate bulky tumors poorly after intravenous administration, in part because of specific binding to the target antigen. Experiments presented here demonstrate an analogous phenomenon in micrometastases; poor antibody penetration, attributable to a ''binding-site barrier'' phenomenon, can be seen in guinea pig micrometastases as small as 300 mu m in diameter. Increasing the dose of antibody can partially overcome this limitation, but at a cost in specificity. C1 NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NCI,CTR CLIN,DEPT NUCL MED,BETHESDA,MD 20892. NR 39 TC 94 Z9 95 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 12 PY 1995 VL 92 IS 19 BP 8999 EP 9003 DI 10.1073/pnas.92.19.8999 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RU759 UT WOS:A1995RU75900095 PM 7568060 ER PT J AU BRODER, CC BERGER, EA AF BRODER, CC BERGER, EA TI FUSOGENIC SELECTIVITY OF THE ENVELOPE GLYCOPROTEIN IS A MAJOR DETERMINANT OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TROPISM FOR CD4(+) T-CELL LINES VS PRIMARY MACROPHAGES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CELL FUSION; BETA-GALACTOSIDASE REPORTER GENE; SYNCYTIA FORMATION; VIRUS ENTRY; RECOMBINANT VACCINIA VIRUSES ID BACTERIOPHAGE-T7 RNA-POLYMERASE; RECOMBINANT VACCINIA VIRUS; HTLV-III LAV; MEMBRANE-FUSION; MONONUCLEAR PHAGOCYTES; PRODUCTIVE INFECTION; NUCLEOTIDE-SEQUENCE; MURINE CELLS; HIV-1; IDENTIFICATION AB We investigated the relationship between the fusion selectivity of the envelope glycoprotein (env) and the tropism of different human immunodeficiency virus type 1 (HIV-1) isolates for CD4(+) human T-cell lines vs, primary macrophages. Recombinant vaccinia viruses were prepared encoding the envs from several well-characterized HIV-1 isolates with distinct cytotropisms, Cells expressing the recombinant envs were mixed with various CD4(+) partner cell types; cell fusion was monitored by a quantitative reporter gene assay and by syncytia formation, With CD4(+) continuous cell lines as partners (T-cell lines, HeLa cells expressing recombinant CD4), efficient fusion occurred with the envs from T-cell line-tropic isolates (IIIB, LAV, SF2, and RF) but not with the envs from macrophage-tropic isolates (JR-FL, SF162, ADA, and Ba-L). The opposite selectivity pattern was observed with primary macrophages as cell partners; stronger fusion occurred with the envs from the macrophage-tropic than from the T-cell line-tropic isolates. All the envs showed fusion activity with peripheral blood mononuclear cells as partners, consistent with the ability of this cell population to support replication of all the corresponding HIV-1 isolates. These fusion selectivities were maintained irrespective of the cell type used to express env, thereby excluding a role for differential host cell modification. We conclude that the intrinsic fusion selectivity of env plays a major role in the tropism of a HIV-1 isolate for infection of CD4(+) T-cell lines vs, primary macrophages, presumably by determining the selectivity of virus entry and cell fusion. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NR 45 TC 134 Z9 134 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 12 PY 1995 VL 92 IS 19 BP 9004 EP 9008 DI 10.1073/pnas.92.19.9004 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RU759 UT WOS:A1995RU75900096 PM 7568061 ER PT J AU ALLEN, JP MAISTO, SA CONNORS, GJ AF ALLEN, JP MAISTO, SA CONNORS, GJ TI SELF-REPORT SCREENING-TESTS FOR ALCOHOL-PROBLEMS IN PRIMARY-CARE SO ARCHIVES OF INTERNAL MEDICINE LA English DT Review ID GENERAL-PRACTICE; RISK-DRINKING; CAGE; MAST; QUESTIONNAIRES; VALIDATION AB Considering the prevalence of excessive alcohol use, its adverse consequences on physical and emotional well-being, and the high degree of responsivity of early-stage drinking problems to brief intervention, screening for alcohol abuse is warranted in medical practice. We describe several practical self-report tests that can help primary care physicians screen their patients for alcohol abuse. Two of the more popular tests, the Michigan Alcoholism Screening Test and the CAGE (an acronym for questions about cutting down on drinking, annoyance al others' concern about drinking, feeling guilty about drinking, and using alcohol as an eye-opener in the morning), are comparable in sensitivity and specificity. Either test is appropriate, but the brevity of CAGE generally gives it an advantage in a busy medical office. Three new tests, the Alcohol Use Disorders Identification Test, the Adolescent Drinking Index, and the TWEAK also are promising. We offer guidelines for selection of screening tests for primary care practice. C1 SYRACUSE UNIV,SYRACUSE,NY. DEPT PSYCHOL,BUFFALO,NY. RES INST ADDICT,BUFFALO,NY. RP ALLEN, JP (reprint author), NIAAA,6000 EXECUT BLVD,MSC 7003,WILLCO BLDG,SUITE 505,BETHESDA,MD 20892, USA. NR 42 TC 56 Z9 56 U1 4 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern Med. PD SEP 11 PY 1995 VL 155 IS 16 BP 1726 EP 1730 DI 10.1001/archinte.155.16.1726 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA RT780 UT WOS:A1995RT78000003 PM 7654105 ER PT J AU DUNCAN, MK HAYNES, JI PIATIGORSKY, J AF DUNCAN, MK HAYNES, JI PIATIGORSKY, J TI THE CHICKEN BETA-A4-CRYSTALLIN-ENCODING AND BETA-B1-CRYSTALLIN-ENCODING GENES ARE TIGHTLY LINKED SO GENE LA English DT Article DE INTRON SIZE; GENE EXPRESSION; EYE LENS; EVOLUTION ID B-CRYSTALLIN GENE; ALPHA-CRYSTALLIN; LENS CRYSTALLINS; DELTA-CRYSTALLIN; EYE LENS; EVOLUTION; PROTEINS; FAMILY; SEQUENCE; EXPRESSION AB Analysis of the 5' flanking region of the chicken beta B1-crystallin-encoding gene (beta B1-cry) revealed regions of sequence homology with the bovine beta A4-crystallin-encoding gene (beta A4-cry). Subsequently, the chicken beta A4-cry cDNA sequence was determined, and it was demonstrated that beta A4- and beta B1-cry are linked head to head in the chicken chromosome with 2147 nucleotides (nt) of intergenic spacer. Chicken beta A4-cry contains six exons, with the first exon being noncoding. Chicken beta A4-cry is the smallest beta-cry ever described, due to the small size of its introns which range in length from 68 to 96 nt. While three polymorphisms were noted between some cDNA clones and the genomic sequence, Southern blot analysis demonstrated that beta A4-cry exists as a single copy in the chicken genome. Northern blot analysis indicated that beta A4-cry is a lens-specific transcript which is expressed at higher levels in the embryo than in the adult. The beta A4-cry mRNA is present at 400-fold lower levels than the beta B1-cry mRNA in the 14-day embryonic chicken lens, and at 2000-fold lower levels than the beta B1-cry mRNA in the adult lens. These results are consistent with the idea that the beta-cry family was once clustered in the chromosome as the gamma-cry family is today, and raises the possibility that the relatively low expression of beta A4-cry is mechanistically linked to the high expression of beta B1-cry in the chicken lens. C1 NEI, MOLEC & DEV BIOL LAB, BETHESDA, MD 20892 USA. NR 49 TC 17 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 EI 1879-0038 J9 GENE JI Gene PD SEP 11 PY 1995 VL 162 IS 2 BP 189 EP 196 DI 10.1016/0378-1119(95)00363-B PG 8 WC Genetics & Heredity SC Genetics & Heredity GA RW351 UT WOS:A1995RW35100003 PM 7557428 ER PT J AU SHULL, JD ESUMI, N COLWELL, AS PENNINGTON, KL JENDOUBI, M AF SHULL, JD ESUMI, N COLWELL, AS PENNINGTON, KL JENDOUBI, M TI SEQUENCE OF THE PROMOTER REGION OF THE MOUSE GENE ENCODING ORNITHINE AMINOTRANSFERASE SO GENE LA English DT Note DE GENE STRUCTURE; RECOMBINANT DNA; REGULATORY REGION; HUMAN OAT; RAT OAT; GYRATE ATROPHY; NUCLEOTIDE SEQUENCE ID GYRATE ATROPHY; DELTA-AMINOTRANSFERASE; GLUTAMINE-SYNTHETASE; MESSENGER-RNA; RAT-LIVER; HEPATOCYTES; EXPRESSION; ESTROGEN AB We have isolated and sequenced the promoter region of the mouse gene (mOAT) encoding ornithine aminotransferase. A comparison of these mOAT sequences with previously reported sequences for the rat and human genes encoding .OAT, rOAT and hOAT, respectively, revealed a 256-bp region flanking the transcription start point that is highly conserved between the three genes. This region contains sequence motifs resembling binding sites for general transcription factors, as well as other traits-acting regulatory proteins. C1 UNIV NEBRASKA,MED CTR,DEPT BIOCHEM & MOLEC BIOL,OMAHA,NE 68198. NEI,IMMUNOL LAB,GENET & MOLEC IMMUNOL SECT,BETHESDA,MD 20892. RP SHULL, JD (reprint author), UNIV NEBRASKA,MED CTR,EPPLEY INST RES CANC & ALLIED DIS,600 S 42ND ST,OMAHA,NE 68198, USA. FU NCI NIH HHS [CA36727]; NICHD NIH HHS [HD24189] NR 21 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD SEP 11 PY 1995 VL 162 IS 2 BP 275 EP 277 DI 10.1016/0378-1119(95)00309-T PG 3 WC Genetics & Heredity SC Genetics & Heredity GA RW351 UT WOS:A1995RW35100018 PM 7557443 ER PT J AU YU, JC DESEABRA, AJJ WANG, LM FLEMING, TP CHEDID, M MIKI, T HEIDARAN, MA AF YU, JC DESEABRA, AJJ WANG, LM FLEMING, TP CHEDID, M MIKI, T HEIDARAN, MA TI AN UNEXPECTED TRANSFORMING GENE IN CALF-THYMUS CARRIER DNA - BOVINE HST SO GENE LA English DT Note DE TRANSFORMATION; FIBROBLAST GROWTH FACTOR FAMILY; RECOMBINATION ID EXPRESSION CDNA CLONING AB During a search for transforming genes by transfecting a human cDNA expression library together with calf thymus carrier-DNA into NIH/3T3 cells, we found a focus which was induced by a plasmid containing a sequence highly homologous to human HST (a transforming gene from Human STomach cancer). However, PCR analysis identified the source of this sequence as calf thymus DNA. The deduced amino acid (aa) sequence of bovine HST shows 91 and 81% identity to the human and mouse HST aa sequences, respectively. These data suggest that the hst of calf thymus carrier-DNA could induce transformation of NIH/3T3 cells. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. WASHINGTON UNIV,SCH MED,DEPT OPHTHALMOL,ST LOUIS,MO 63110. NR 5 TC 3 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD SEP 11 PY 1995 VL 162 IS 2 BP 333 EP 334 DI 10.1016/0378-1119(95)00330-9 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA RW351 UT WOS:A1995RW35100030 PM 7557455 ER PT J AU WONG, ML LODDICK, SA BONGIORNO, PB GOLD, PW ROTHWELL, NJ LICINIO, J AF WONG, ML LODDICK, SA BONGIORNO, PB GOLD, PW ROTHWELL, NJ LICINIO, J TI FOCAL CEREBRAL-ISCHEMIA INDUCES CRH MESSENGER-RNA IN RAT CEREBRAL-CORTEX AND AMYGDALA SO NEUROREPORT LA English DT Article DE CORTICOTROPIN-RELEASING HORMONE; CEREBRAL ISCHEMIA; CEREBRAL CORTEX; AMYGDALA; PARAVENTRICULAR HYPOTHALAMIC NUCLEUS; IN SITU HYBRIDIZATION; DENSITOMETRY ID CORTICOTROPIN-RELEASING-FACTOR; IMMUNOREACTIVITY; RECEPTORS; HORMONE; DISEASE AB CORTICOTROPIN-releasing hormone (CRH) antagonism has neuroprotective effects in models of ischemia. We examined CRH mRNA by in situ hybridization in a well-established rat model of focal cerebral ischemia caused by permanent middle cerebral artery occlusion (MCAo). In ischemic cortex CRH mRNA levels were elevated 2.6-fold 60 min after MCAo, compared with sham operated animals. CRH mRNA was also induced in the amygdala, 60 min following ischemia, in a pattern which was qualitatively different from that of sham operated animals. This rapid and profound increase in CRH mRNA levels during focal cerebral ischemia is likely to be associated with neurotoxicity, as CRH antagonism has been reported to cause a significant reduction in neuronal loss during ischemia. C1 UNIV MANCHESTER,SCH BIOL SCI,MANCHESTER M13 9PT,LANCS,ENGLAND. RP WONG, ML (reprint author), NIMH,INTRAMURAL RES PROGRAM,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892, USA. RI Wong, Ma-Li/D-7903-2011; Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 FU Wellcome Trust NR 25 TC 44 Z9 47 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 SEP 11 PY 1995 VL 6 IS 13 BP 1785 EP 1788 DI 10.1097/00001756-199509000-00019 PG 4 WC Neurosciences SC Neurosciences & Neurology GA RW478 UT WOS:A1995RW47800019 PM 8541482 ER PT J AU LUSTIG, B LIN, NH SMITH, SM JERNIGAN, RL JEANG, KT AF LUSTIG, B LIN, NH SMITH, SM JERNIGAN, RL JEANG, KT TI A SMALL MODIFIED HAMMERHEAD RIBOZYME AND ITS CONFORMATIONAL CHARACTERISTICS DETERMINED BY MUTAGENESIS AND LATTICE CALCULATION SO NUCLEIC ACIDS RESEARCH LA English DT Article ID 3-DIMENSIONAL STRUCTURE; SEQUENCE REQUIREMENTS; SELF-CLEAVAGE; TRANSFER-RNA; PROTEIN; MODEL AB A prototypic hammerhead ribozyme has three helices that surround an asymmetrical central core loop, We have mutagenized a hammerhead type ribozyme, In agreement with previous studies, progressive removal of stem-loop II from a three stemmed ribozyme showed that this region is not absolutely critical for catalysis, However, complete elimination of stem II and its loop did reduce, but did not eliminate, function, In a stem-loop II-deleted ribozyme, activity was best preserved when a purine, preferably a G, was present at position 10.1, This G contributed to catalysis irregardless of its role as either one part of a canonical pair with a C residue at 11.1 or a lone nucleotide with C (11.1) deleted, Computational methods using lattices generated 87 million three-dimensional chain forms for a stem-loop II-deleted RNA complex that preserved one potential G . C base pair at positions 10.1 and 11.1, This exhaustive set of chain forms included one major class of structures with G(10.1) being spatially proximal to the GUCX cleavage site of the substrate strand, Strong correlations were observed between colinear arrangement of stems I and III, constraints of base-pairing in the central core loop, and one particular placement of G(10.1) relative to the cleavage site, Our calculations of a stem-loop II-deleted ribozyme indicate that without needing to invoke any other constraints, the inherent asymmetry in the lengths of the two loop strands (3 nt in one and 7 nt in the other) that compose the core and flank G10.1-C11.1 stipulated strongly this particular G placement, This suggests that the hammerhead ribozyme maintains an asymmetry in its internal loop for a necessary structure/function reason. C1 NIAID,MOLEC MICROBIOL LAB,MOLEC VIROL SECT,BETHESDA,MD 20892. NCI,MATH BIOL LAB,BETHESDA,MD 20892. RI Jernigan, Robert/A-5421-2012; Jeang, Kuan-Teh/A-2424-2008 FU NIAID NIH HHS [K08 AI081545] NR 41 TC 7 Z9 7 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP 11 PY 1995 VL 23 IS 17 BP 3531 EP 3538 DI 10.1093/nar/23.17.3531 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RX940 UT WOS:A1995RX94000024 PM 7567466 ER PT J AU BORODOVSKY, M MCININCH, JD KOONIN, EV RUDD, KE MEDIGUE, C DANCHIN, A AF BORODOVSKY, M MCININCH, JD KOONIN, EV RUDD, KE MEDIGUE, C DANCHIN, A TI DETECTION OF NEW GENES IN A BACTERIAL GENOME USING MARKOV-MODELS FOR 3 GENE CLASSES SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ESCHERICHIA-COLI GENOME; DNA-SEQUENCE; CODON USAGE; REGION; MINUTES; PROTEIN; EXPRESSIVITY; DATABASES AB We further investigated the statistical features of the three classes of Escherichia coli genes that have been previously delineated by factorial correspondence analysis and dynamic clustering methods, A phased Markov model for a nucleotide sequence of each gene class was developed and employed for gene prediction using the GeneMark program, The protein-coding region prediction accuracy was determined for class-specific Markov models of different orders when the programs implementing these models were applied to gene sequences from the same or other classes. It is shown that at least two training sets and two program versions derived for different classes of E.coli genes are necessary in order to achieve a high accuracy of coding region prediction for uncharacterized sequences, Some annotated E.coli genes from Class I and Class III are shown to be spurious, whereas many open reading frames (ORFs) that have not been annotated in GenBank as genes are predicted to encode proteins, The amino acid sequences of the putative products of these ORFs initially did not show similarity to already known proteins. However, conserved regions have been identified in several of them by screening the latest entries in protein sequence databases and applying methods for motif search, while some other of these new genes have been identified in independent experiments. C1 NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20894 USA. INST CURIE, F-75231 PARIS 05, FRANCE. INST PASTEUR, F-75724 PARIS 15, FRANCE. RP GEORGIA INST TECHNOL, SCH BIOL, ATLANTA, GA 30332 USA. FU NHGRI NIH HHS [HG00783]; NIGMS NIH HHS [GM47853] NR 31 TC 76 Z9 131 U1 0 U2 0 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 SEP 11 PY 1995 VL 23 IS 17 BP 3554 EP 3562 DI 10.1093/nar/23.17.3554 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RX940 UT WOS:A1995RX94000027 PM 7567469 ER PT J AU MANGANIELLO, VC MURATA, T TAIRA, M BELFRAGE, P DEGERMAN, E AF MANGANIELLO, VC MURATA, T TAIRA, M BELFRAGE, P DEGERMAN, E TI DIVERSITY IN CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE ISOENZYME FAMILIES SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Review ID PHOTORECEPTOR CGMP-PHOSPHODIESTERASE; AMP-SPECIFIC PHOSPHODIESTERASE; CONGESTIVE-HEART-FAILURE; GROWTH FACTOR-I; CALMODULIN-STIMULATED PHOSPHODIESTERASE; SENSITIVE CAMP PHOSPHODIESTERASE; RECENT CLINICAL DEVELOPMENTS; POSITIVE INOTROPIC AGENTS; AMINO-ACID-SEQUENCE; BETA-SUBUNIT GENE C1 LUND UNIV,SCH MED,DEPT MED & PHYSIOL CHEM,LUND,SWEDEN. RP MANGANIELLO, VC (reprint author), NHLBI,BIOCHEM PHYSIOL SECT,PULM CRIT CARE MED BRANCH,BLDG 10,ROOM 5N-307,BETHESDA,MD 20892, USA. NR 155 TC 192 Z9 196 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD SEP 10 PY 1995 VL 322 IS 1 BP 1 EP 13 DI 10.1006/abbi.1995.1429 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RU852 UT WOS:A1995RU85200001 PM 7574662 ER PT J AU DAVIS, DA BRANCA, AA PALLENBERG, AJ MARSCHNER, TM PATT, LM CHATLYNNE, LG HUMPHREY, RW YARCHOAN, R LEVINE, RL AF DAVIS, DA BRANCA, AA PALLENBERG, AJ MARSCHNER, TM PATT, LM CHATLYNNE, LG HUMPHREY, RW YARCHOAN, R LEVINE, RL TI INHIBITION OF THE HUMAN IMMUNODEFICIENCY VIRUS-1 PROTEASE AND HUMAN IMMUNODEFICIENCY VIRUS-1 REPLICATION BY BATHOCUPROINE DISULFONIC ACID CU1+ SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE HUMAN IMMUNODEFICIENCY VIRUS-1; PROTEASE; COPPER CHLORIDE; COPPER CHELATE; ANTIVIRALS; POLYPROTEIN PROCESSING ID SYNTHETIC HIV-1 PROTEASE; ANTIVIRAL ACTIVITY; RETROVIRAL PROTEASES; VIRAL INFECTIVITY; TYPE-1 PROTEASE; PROTEINASE; INVITRO; DESIGN; AIDS; MATURATION AB The protease encoded by the human immunodeficiency virus-1 (HIV-1) is essential for processing viral polyproteins which contain the enzymes and structural proteins required for the infectious virus. It was previously found that cupric chloride, in the presence of dithiothreitol or ascorbic acid, could inhibit the HIV-1 protease. It was suggested that a Cu1+ chelate was the moiety responsible for inhibition of the protease. This hypothesis has now been investigated directly by utilizing the stable Cu1+ chelate, bathocuproine disulfonic acid Cu1+ (BCDS-Cu1+). BCDS-Cu1+ inhibited the HIV-1 wild type protease as well as a mutant HIV-1 protease lacking cysteines, BCDS-Cu1+ was a competitive inhibitor of the mutant HIV-1 protease with an apparent K-i of 1 mu M. Replication of HIV-1 in human lymphocytes and the cytotoxic effect of HIV-1 in CEM cells was inhibited by micromolar BCDS-Cu1+. Inhibition of the protease and of HIV replication by BCDS-Cu1+ was dependent on the presence of Cu1+ as BCDS alone was ineffective. EDTA blocked the inhibition of the protease by Cu1+ but was unable to block inhibition of the protease by BCDS-Cu1+, indicating that the Cu1+ complex was the inhibitory agent. The apparent IC50 for BCDS-Cu1+ on the inhibition of replication by primary isolates of HIV-1 was 5 mu M. However, BCDS-Cu1+ did not affect polyprotein processing in an H9 cell line chronically infected with HIV-1, indicating that BCDS-Cu1+ acts by yet another mechanism to block HIV infection. Other possible targets for BCDSCu1+ include inhibition of viral adsorption and/or inhibition of the HIV-1 integrase. C1 PROCYTE CORP,KIRKLAND,WA 98034. ADV BIOTECHNOL INC,COLUMBIA,MD 21046. NCI,MED BRANCH,BETHESDA,MD. RP DAVIS, DA (reprint author), NHLBI,IR,BIOCHEM LAB,BLDG 3,RM 106,3 CTR DR,MSC 0320,BETHESDA,MD 20892, USA. RI Levine, Rodney/D-9885-2011 NR 52 TC 23 Z9 23 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD SEP 10 PY 1995 VL 322 IS 1 BP 127 EP 134 DI 10.1006/abbi.1995.1444 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RU852 UT WOS:A1995RU85200016 PM 7574666 ER PT J AU CHUNG, KN ROBERTS, S KIM, CH KIRASSOVA, M TREPEL, J ELWOOD, PC AF CHUNG, KN ROBERTS, S KIM, CH KIRASSOVA, M TREPEL, J ELWOOD, PC TI RAPID TURNOVER AND IMPAIRED CELL-SURFACE EXPRESSION OF THE HUMAN FOLATE RECEPTOR IN MOUSE L(TK-) FIBROBLASTS, A CELL-LINE DEFECTIVE IN GLYCOSYLPHOSPHATIDYLINOSITOL TAIL SYNTHESIS SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID HUMAN KB-CELLS; ANCHORED MEMBRANE-PROTEINS; HUMAN-LEUKEMIA CELLS; BINDING-PROTEIN; GLYCOSYL-PHOSPHATIDYLINOSITOL; PHOSPHOLIPASE-C; MULTIPLE FORMS; CDNA; 5-METHYLTETRAHYDROFOLATE; BIOSYNTHESIS AB The human folate receptor (hFR) is a plasma membrane protein that is anchored to the membrane via a glycosylphosphatidylinositol (GPI) tail in some cell types. The KB hFR cDNA sequence predicts a hydrophobic, alpha-helical 31-residue carboxyl terminus that is thought to be the signal for cleavage and attachment of the GPI tail. Alternatively, this region may serve as a transmembrane domain if GPI attachment is not effcient. In this study, we investigated the latter possibility by expressing the hFR in L(tk-) cells, cells that are unable to synthesize GPI tails for attachment to membrane proteins. We also transfected the same hFR cDNA into Chinese hamster ovary (CHO) cells, cells that can anchor proteins by either a GPI tail or a transmembrane domain. Neither parental cell line expresses detectable levels of folate receptor as determined by folic acid binding assays, Western analysis, or Northern analysis. In L(tk-) cells, we found that the recombinant hFR is not expressed on the cell surface, but is rapidly degraded (t(1/2) less than or equal to 4 h). Most (>95%) of the recombinant hFR remains Endo H sensitive, suggesting retention in the endoplasmic: reticulum. In contrast, transfected CHO cells express functional hFR protein at the cell surface, the half-life of the hFR is long (t(1/2) greater than or equal to 24 h), and the Endo H glycosylation pattern of the recombinant hFR is consistent with normal processing through the Golgi apparatus. Therefore, in the absence of a GPI tail, the hFR is not sorted to the cell surface and the incompletely processed hFR protein is unstable. (C) 1995 Academic Press, Inc. RP CHUNG, KN (reprint author), NCI,MED BRANCH,BLDG 10,ROOM 12N226,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 41 TC 12 Z9 12 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD SEP 10 PY 1995 VL 322 IS 1 BP 228 EP 234 DI 10.1006/abbi.1995.1456 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RU852 UT WOS:A1995RU85200028 PM 7574680 ER PT J AU SUEYOSHI, T PARK, LJ MOORE, R JUVONEN, RO NEGISHI, M AF SUEYOSHI, T PARK, LJ MOORE, R JUVONEN, RO NEGISHI, M TI MOLECULAR ENGINEERING OF MICROSOMAL P450 2A-4 TO A STABLE, WATER-SOLUBLE ENZYME SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE P450; MEMBRANE PROTEIN; BACTERIAL EXPRESSION; PEPTITERGENT; MOUSE; AMPHIPATHIC PEPTIDE; PURIFICATION WITHOUT DETERGENTS ID SITE-DIRECTED MUTAGENESIS; ESCHERICHIA-COLI; AMINO-ACID; SUBSTRATE-SPECIFICITY; MEMBRANE TOPOLOGY; CRYSTAL-STRUCTURE; SIGNAL ANCHOR; CYTOCHROME-P450; EXPRESSION; LIVER AB Peptitergented P450 2a-4 (Pepti-P450), a water-soluble form of the mouse microsomal P450 2a-4, was genetically engineered and expressed in Escherichia coli. The NH2-terminal hydrophobic sequence (positions 2 to 19) of Pepti-P450 was replaced by a peptitergent PD1, amphipathic peptide consisting of 24 residues (C. E. Schafmeister, L. J. Miercke, and R. M. Stroud (1993) Science 262, 734-738), The expression level of Pepti-P450 (90,000 molecules/cell) was at least four times greater than that of wild-type P450 2a-4. Since Pepti-P450 was quite stable and was expressed as a peripheral membrane protein, it can be easily purified from the membrane fraction treated with Na2CO3 without using any detergents during the chromatographic steps. The purified Pepti-P450 retained the spectral and catalytic properties of the unmodified enzyme with a similar K-m value for steroid 15 alpha-hydroxylase activity (19.7 mu M in comparison to 14.2 mu M of the wildtype). Gel permeation chromatography showed that the purified Pepti-P450 in the detergent-free buffer was an oligomer with an approximate molecular mass of 450 kDa. The replacement of the hydrophobic anchor domain with an amphipathic helix such as peptitergent, therefore, may provide a general method for engineering membrane-bound P450s to soluble enzymes. (C) 1995 Academic Press, Inc. RP SUEYOSHI, T (reprint author), NIEHS,REPROD & DEV TOXICOL LAB,PHARMACOGENET SECT,RES TRIANGLE PK,NC 27709, USA. NR 36 TC 30 Z9 33 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD SEP 10 PY 1995 VL 322 IS 1 BP 265 EP 271 DI 10.1006/abbi.1995.1461 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RU852 UT WOS:A1995RU85200033 PM 7574685 ER PT J AU MULARD, LA GLAUDEMANS, CPJ AF MULARD, LA GLAUDEMANS, CPJ TI SYNTHESIS OF SPECIFICALLY DEOXYGENATED DISACCHARIDE DERIVATIVES OF THE SHIGELLA-DYSENTERIAE TYPE-1 O-ANTIGEN SO CARBOHYDRATE RESEARCH LA English DT Article DE DEOXYGENATED DISACCHARIDE DERIVATIVES; SHIGELLA DYSENTERIAE; O-ANTIGEN ID ACID RELATED-COMPOUNDS; POLYSACCHARIDE; ANTIBODIES; FLEXNERI AB The synthesis of methyl O-alpha-L-rhamnopyranosyl-(1 --> 2)-alpha-D-galactopyranosides specifically deoxygenated at position 2 (31), or 4 (21) of the rhamnopyranosyl residue was accomplished using methyl 3,4,6-tri-0-benzoyl-alpha-D-galactopyranoside (18) as the glycosyl acceptor. Phenyl thionocarbonate activation of the penta-O-benzoylated disaccharide precursor followed by Barton reduction and Zemplen transesterification gave 31, while 21 was obtained via condensation of the deoxygenated monosaccharide donor with 18, and subsequent debenzoylation of the product. C1 NIDDK,BETHESDA,MD 20892. NR 23 TC 6 Z9 6 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD SEP 8 PY 1995 VL 274 BP 209 EP 222 DI 10.1016/0008-6215(95)00122-A PG 14 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA RX176 UT WOS:A1995RX17600016 PM 7585707 ER PT J AU SAEZ, E RUTBERG, SE MUELLER, E OPPENHEIM, H SMOLUK, J YUSPA, SH SPIEGELMAN, BM AF SAEZ, E RUTBERG, SE MUELLER, E OPPENHEIM, H SMOLUK, J YUSPA, SH SPIEGELMAN, BM TI C-FOS IS REQUIRED FOR MALIGNANT PROGRESSION OF SKIN TUMORS SO CELL LA English DT Article ID MOUSE SKIN; TRANSGENIC MICE; GENE-EXPRESSION; CELL CARCINOMAS; PHORBOL ESTERS; RETINOIC ACID; NULL MUTATION; BENIGN-TUMORS; HUMAN-BREAST; JUN AB The proto-oncogene c-fos is a major nuclear target for signal transduction pathways involved in the regulation of cell growth, differentiation, and transformation. Using the multistep skin carcinogenesis model, we have directly tested the ability of c-fos-deficient mice to develop cancer. Upon treatment with a tumor promoter, c-fos knockout mice carrying a v-H-ras transgene were able to develop benign tumors with similar kinetics and relative incidence as wild-type animals. However, c-fos-deficient papillomas quickly became very dry and hyperkeratinized, taking on an elongated, horny appearance. While wild-type papillomas eventually progressed into malignant tumors, c-fos-deficient tumors failed to undergo malignant conversion. Experiments in which v-H-ras-expressing keratinocytes were grafted onto nude mice suggest that c-fos-deficient cells have an intrinsic defect that hinders tumorigenesis. These results demonstrate that a member of the AP-1 family of transcription factors is required for the development of a malignant tumor. C1 HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. RP SAEZ, E (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. FU NICHD NIH HHS [HD27295] NR 60 TC 303 Z9 310 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD SEP 8 PY 1995 VL 82 IS 5 BP 721 EP 732 DI 10.1016/0092-8674(95)90469-7 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RU755 UT WOS:A1995RU75500007 PM 7545543 ER PT J AU VOGEL, KS BRANNAN, CI JENKINS, NA COPELAND, NG PARADA, LF AF VOGEL, KS BRANNAN, CI JENKINS, NA COPELAND, NG PARADA, LF TI LOSS OF NEUROFIBROMIN RESULTS IN NEUROTROPHIN-INDEPENDENT SURVIVAL OF EMBRYONIC SENSORY AND SYMPATHETIC NEURONS SO CELL LA English DT Article ID NERVE GROWTH-FACTOR; NUCLEOTIDE EXCHANGE FACTOR; TRK PROTOONCOGENE PRODUCT; DORSAL-ROOT-GANGLIA; TYPE-1 GENE; CAENORHABDITIS-ELEGANS; PROTEIN PRODUCT; TYROSINE KINASE; RAS P21; MOUSE AB Mutations at the neurofibromatosis 1 (NF1) locus in humans and mice result in abnormal growth of neural crest-derived cells, including melanocytes and Schwann cells. We have exploited a targeted disruption of the NF1 gene in mice to examine the role of neurofibromin in the acquisition of neurotrophin dependence in embryonic neurons. We show that both neural crest- and placode-derived sensory neurons isolated from NF1 (-/-) embryos develop, extend neurites, and survive in the absence of neurotrophins, whereas their wild-type counterparts die rapidly unless nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF) is added to the culture medium. Moreover, NF1 (-/-) sympathetic neurons survive for extended periods and acquire mature morphology in the presence of NGF-blocking antibodies. Our results are consistent with a model wherein neurofibromin acts as a negative regulator of neurotrophin-mediated signaling for survival of embryonic peripheral neurons. C1 NCI,FREDERICK CANC RES & DEV CTR,ADV BIOSCI LABS,BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RP VOGEL, KS (reprint author), UNIV TEXAS,SW MED CTR,CTR DEV BIOL,5323 HARRY HINES BLVD,DALLAS,TX 75235, USA. RI Parada, luis/B-9400-2014 FU NCI NIH HHS [N01-CO-74101] NR 58 TC 124 Z9 124 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD SEP 8 PY 1995 VL 82 IS 5 BP 733 EP 742 DI 10.1016/0092-8674(95)90470-0 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RU755 UT WOS:A1995RU75500008 PM 7671302 ER PT J AU LEVIN, M JOHNSON, RL STERN, CD KUEHN, M TABIN, C AF LEVIN, M JOHNSON, RL STERN, CD KUEHN, M TABIN, C TI A MOLECULAR PATHWAY DETERMINING LEFT-RIGHT ASYMMETRY IN CHICK EMBRYOGENESIS SO CELL LA English DT Article ID AXIAL STRUCTURES; BODY ASYMMETRY; EMBRYO; PATTERN; ACTIVIN; BLASTODERM; EXPRESSION; INDUCTION; MUTATION; HEART AB While significant progress has been made in understanding the molecular events underlying the early specification of the antero-posterior and dorso-ventral axes, little information is available regarding the cellular or molecular basis for left-right (LR) differences in animal morphogenesis. We describe the expression patterns of three genes involved in LR determination in chick embryos: activin receptor IIa, Sonic hedgehog (Shh), and cNR-1 (related to the mouse gene nodal). These genes are expressed asymmetrically during and after gastrulation and regulate the expression of one another in a sequential pathway. Moreover, manipulation of the sidedness of either activin protein or Shh expression alters heart situs. Together, these observations identify a cascade of molecular asymmetry that determines morphological LR asymmetry in the chick embryo. C1 COLUMBIA UNIV,COLL PHYS & SURG,DEPT GENET & DEV,NEW YORK,NY 10032. NIH,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RP LEVIN, M (reprint author), HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115, USA. RI Stern, Claudio/C-6265-2008; Kuehn, Michael/A-4573-2014 OI Stern, Claudio/0000-0002-9907-889X; Kuehn, Michael/0000-0002-7703-9160 NR 53 TC 546 Z9 552 U1 1 U2 18 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD SEP 8 PY 1995 VL 82 IS 5 BP 803 EP 814 DI 10.1016/0092-8674(95)90477-8 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RU755 UT WOS:A1995RU75500015 PM 7671308 ER PT J AU MORROW, DM MORROW, M TAGLE, DA SHILOH, Y COLLINS, FS HIETER, P AF MORROW, DM MORROW, M TAGLE, DA SHILOH, Y COLLINS, FS HIETER, P TI TEL1, AN SACCHAROMYCES-CEREVISIAE HOMOLOG OF THE HUMAN GENE MUTATED IN ATAXIA-TELANGIECTASIA, IS FUNCTIONALLY RELATED TO THE YEAST CHECKPOINT GENE MEC1 SO CELL LA English DT Article ID SACCHAROMYCES-CEREVISIAE; PHOSPHATIDYLINOSITOL 3-KINASE; RADIATION SENSITIVITY; PROTEIN; CELLS; CANCER; DNA; RAPAMYCIN; VPS34; IDENTIFICATION AB Patients with the genetic disorder ataxia telangiectasia (AT) have mutations in the AT mutated (ATM) gene, which is homologous to TEL1 and the checkpoint gene MEC1. A tel1 deletion mutant, unlike a mec1 deletion, is viable and does not exhibit increased sensitivity to DNA-damaging agents. However, increased dosage of TEL1 rescues sensitivity of a mec1 mutant, mec1-1, to DNA-damaging agents and rescues viability of a mec1 disruption. mec1-1 tel1 Delta 1 double mutants are synergistically sensitive to DNA-damaging agents, including radiomimetic drugs. These data indicate that TEL1 and MEC1 are functionally related and that functions of the ATM gene are apparently divided between at least two S. cerevisiae homologs. C1 NIH,NATL CTR HUMAN GENOME RES,GENE TRANSFER LAB,BETHESDA,MD 20892. TEL AVIV UNIV,SACKLER SCH MED,DEPT HUMAN GENET,IL-69978 TEL AVIV,ISRAEL. RP MORROW, DM (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT MOLEC BIOL & GENET,BALTIMORE,MD 21205, USA. FU NCI NIH HHS [CA16519]; NIGMS NIH HHS [GM162283]; NINDS NIH HHS [NS31763] NR 48 TC 318 Z9 320 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD SEP 8 PY 1995 VL 82 IS 5 BP 831 EP 840 DI 10.1016/0092-8674(95)90480-8 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RU755 UT WOS:A1995RU75500018 PM 7545545 ER PT J AU GERGEL, D MISIK, V ONDRIAS, K CEDERBAUM, AI AF GERGEL, D MISIK, V ONDRIAS, K CEDERBAUM, AI TI INCREASED CYTOTOXICITY OF 3-MORPHOLINOSYDNONIMINE TO HEPG2 CELLS IN THE PRESENCE OF SUPEROXIDE-DISMUTASE - ROLE OF HYDROGEN-PEROXIDE AND IRON SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NITRIC-OXIDE; LIPID-PEROXIDATION; CYTO-TOXICITY; FREE-RADICALS; URIC-ACID; PEROXYNITRITE; HYDROXYL; COMPLEXES; OXYGEN; CARDIOPROTECTION AB 3-Morpholinosydnonimine (SIN-1) is widely used to generate nitric oxide (NOx.) and superoxide radical (Oa. The effect of SOD on the toxicity of SIN-1 is complex, depending on what is the ultimate species responsible for toxicity. SIN-1 (<1 mM) was only slightly toxic to HepG2 cells, Copper,zinc superoxide dismutase (Cu,Zn-SOD) or manganese superoxide dismutase (Mn-SOD) increased the toxicity of SIN-1. Catalase abolished, while sodium azide potentiated, this toxicity, suggesting a key role for H2O2 in the overall mechanism. Depletion of GSH from the HepG2 cells also potentiated the toxicity of SIN-1 plus SOD, Although Me(2)SO, sodium formate, and mannitol had no protective effect, iron chelators, thiourea and urate protected the cells against the SIN-1 plus Cu,Zn-SOD-mediated cytotoxicity. The cytotoxic effect of Cu,Zn-SOD but not Mn-SOD, showed a biphasic dose response being most pronounced at lower concentrations (10-100 units/ml). In the presence of SIN-1, Mn-SOD increased accumulation of H2O2 in a concentration-dependent manner. In contrast, Cu,Zn-SOD increased H2O2 accumulation from SIN-1 at low but not high concentrations of the enzyme, suggesting that high concentrations of the Cu,Zn-SOD interacted with the H2O2. EPR spin trapping studies demonstrated the formation of hydroxyl radical from the decomposition of H2O2 by high concentrations of the Cu,Zn-SOD. The cytotoxic effect of the NO donors SNAP and DEA/NO was only slightly enhanced by SOD; catalase had no effect, Thus, the oxidants responsible for the toxicity of SIN-1 and SNAP or DEA\NO to HepG2 cells under these conditions are different, with H2O2 derived from O-2-radical-anion dismutation playing a major role with SIN-1, These results suggest that the potentiation of SIN-1 toxicity by SOD is due to enhanced production of H2O2, followed by site-specific damage of critical cellular sites by a transition metal-catalyzed reaction, These results also emphasize that the role of SOD as a protectant against oxidant damage is complex and dependent, in part, on the subsequent fate and reactivity of the generated H2O2. C1 CUNY MT SINAI SCH MED,DEPT BIOCHEM,NEW YORK,NY 10029. CUNY MT SINAI SCH MED,DEPT MED,NEW YORK,NY 10029. NCI,BETHESDA,MD 20892. FU NIAAA NIH HHS [AA-03312, AA-09460] NR 61 TC 57 Z9 57 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 8 PY 1995 VL 270 IS 36 BP 20922 EP 20929 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RU054 UT WOS:A1995RU05400012 PM 7673115 ER PT J AU HAMANAKA, R SMITH, MR OCONNOR, PM MALOID, S MIHALIC, K SPIVAK, JL LONGO, DL FERRIS, DK AF HAMANAKA, R SMITH, MR OCONNOR, PM MALOID, S MIHALIC, K SPIVAK, JL LONGO, DL FERRIS, DK TI POLO-LIKE KINASE IS A CELL-CYCLE-REGULATED KINASE ACTIVATED DURING MITOSIS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; CDC2 PROTEIN-KINASE; PHOSPHORYLATION SITES; DEPENDENT KINASES; MESSENGER-RNA; IDENTIFICATION; DROSOPHILA; DEPHOSPHORYLATION; CHECKPOINTS; DIVISION AB Previously, we demonstrated that expression of polo-like kinase (PLK) is required for cellular DNA synthesis and that overexpression of PLK is sufficient to induce DNA synthesis. We now report that the endogenous levels of PLK, its phosphorylation status, and protein kinase activity are tightly regulated during cell cycle progression. PLK protein is low in G(1), accumulates during S and G(2)M, and is rapidly reduced after mitosis. During mitosis, PLK is phosphorylated on serine, and its serine threonine kinase function is activated at a time close to that of p34(cdc2). The phosphorylated form of PLK migrates with reduced mobility on SDS-polyacrylamide gel electrophoresis, and dephosphorylation by purified protein phosphatase 2A converts it to the more rapidly migrating form and reduces the total amount of PLK kinase activity. Purified p34(cdc2)-cyclin B complex can phosphorylate PLK protein in vitro but causes little increase in PLK kinase activity. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DIV HEMATOL,BALTIMORE,MD 21205. NR 41 TC 151 Z9 153 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 8 PY 1995 VL 270 IS 36 BP 21086 EP 21091 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RU054 UT WOS:A1995RU05400036 PM 7673138 ER PT J AU THOMAS, DC VEAUTE, X FUCHS, RPP KUNKEL, TA AF THOMAS, DC VEAUTE, X FUCHS, RPP KUNKEL, TA TI FREQUENCY AND FIDELITY OF TRANSLESION SYNTHESIS OF SITE-SPECIFIC N-2-ACETYLAMINOFLUORENE ADDUCTS DURING DNA-REPLICATION IN A HUMAN CELL EXTRACT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DOUBLE-STRANDED DNA; UV-IRRADIATED DNA; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; REPETITIVE SEQUENCES; ANGSTROM RESOLUTION; MUTAGENESIS; POLYMERASE; MUTATIONS; INVITRO AB We have previously analyzed the effects of site-specific N-2-acetylaminofluorene (AAF) adducts on the efficiency and frameshift fidelity of SV40-based DNA replication in a human cell extract (Thomas, D. C., Veaute, X,, Kunkel, T. A., and Fuchs, R. P. P. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 7752-7756). Here we use two sets of substrates to examine the probability of replication termination and error-free and error-prone bypass of AAF adducts. The substrates contained site-specific adducts at one of three guanines in a NarI sequence (5'-GGCGCC-3') placed within the lacZ alpha reporter gene and located on the template for either leading or lagging strand replication. The presence of the adduct at any position strongly reduces the efficiency of a single round of replication in a HeLa cell extract, Product analysis reveals preferential replication of the undamaged strand and termination of replication of the damaged strand occurring one nucleotide before incorporation opposite either a leading or lagging strand adduct, Products resistant to restriction endonuclease cleavage at the adducted site were generated in amounts consistent with 16-48% lesion bypass during replication, Most of this bypass was error-free, However, two-nucleotide deletion errors were detected in the replication products of DNA containing an AAF adduct in either the leading or lagging strand, but only when present at the third guanine position. Collectively, the data suggest that the replication apparatus in a HeLa cell extract generates a template-primer slippage error at an AAF adduct once for every 30-100 bypass events. C1 NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. ECOLE SUPER BIOTECHNOL STRASBOURG,CNRS,UPR CANCEROGENESE & MUTAGENESE & STRUCT,F-67400 ILLKIRCH GRAFFENS,FRANCE. NR 36 TC 27 Z9 27 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 8 PY 1995 VL 270 IS 36 BP 21226 EP 21233 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RU054 UT WOS:A1995RU05400056 PM 7673156 ER PT J AU RUSS, G ESQUIVEL, F YEWDELL, JW CRESSWELL, P SPIES, T BENNICK, JR AF RUSS, G ESQUIVEL, F YEWDELL, JW CRESSWELL, P SPIES, T BENNICK, JR TI ASSEMBLY, INTRACELLULAR-LOCALIZATION, AND NUCLEOTIDE-BINDING PROPERTIES OF THE HUMAN PEPTIDE TRANSPORTERS TAP1 AND TAP2 EXPRESSED BY RECOMBINANT VACCINIA VIRUSES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I MOLECULES; ENDOPLASMIC-RETICULUM; ANTIGEN PRESENTATION; MEMBRANE-PROTEINS; ABC TRANSPORTER; LYMPHOCYTES-T; MHC; REGION; TRANSLOCATION AB The transporter associated with antigen processing (TAP) transports short peptides from the cytosol to the endoplasmic reticulum, where peptides assemble with class I molecules of the major histocompatibility complex, TAP is comprised of two subunits, termed TAP1 and TAP2, We produced recombinant vaccinia viruses that direct synthesis of the TAP subunits, either individually or together, Virus-encoded TAP is rapidly and efficiently assembled (t(1/2) of 5 min or less) by cells and does not spontaneously assemble in detergent extracts, By confocal immunofluorescence microscopy, TAP1 when expressed alone or with TAP2 is largely, if not exclusively, localized to the endoplasmic reticulum, Metabolic labeling with [2-H-3]mannose demonstrates that TAP1 (but not TAP2) possesses Asn-Linked oligosaccharides, but the lack of binding of [S-35]methionine-labeled TAP to concanavalin A-agarose suggests that the glycosylated form represents a minor population of TAP1, The two subunits of the assembled complex present in detergent extracts photolabeled equally with 8-azido-[alpha-P-32]ATP. Photolabeling of the two subunits was inhibited in parallel by various di- and trinucleotides, suggesting that their nucleotide binding sites function in a highly similar manner, Incubation of detergent extracts at 37 degrees C results in the rapid loss of TAP1 immunoreactivity, indicating either an unusual sensitivity to proteases or an irreversible conformation alteration. C1 YALE UNIV,HOWARD HUGHES MED INST,NEW HAVEN,CT 06510. DANA FARBER CANC INST,BOSTON,MA 02115. RP RUSS, G (reprint author), NIAID,VIRAL DIS LAB,BLDG 4,ROOM 205,BETHESDA,MD 20892, USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 56 TC 69 Z9 69 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 8 PY 1995 VL 270 IS 36 BP 21312 EP 21318 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RU054 UT WOS:A1995RU05400068 PM 7673167 ER PT J AU MILLER, RW AF MILLER, RW TI THE DISCIPLINE OF EPIDEMIOLOGY SO SCIENCE LA English DT Letter ID CANCER RP MILLER, RW (reprint author), NCI,GENET EPIDEMIOL BRANCH,EPN 400,BETHESDA,MD 20892, USA. NR 3 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD SEP 8 PY 1995 VL 269 IS 5229 BP 1327 EP 1327 DI 10.1126/science.7660110 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RT806 UT WOS:A1995RT80600005 PM 7660108 ER PT J AU DUAN, DR PAUSE, A BURGESS, WH ASO, T CHEN, DYT GARRETT, KP CONAWAY, RC CONAWAY, JW LINEHAN, WM KLAUSNER, RD AF DUAN, DR PAUSE, A BURGESS, WH ASO, T CHEN, DYT GARRETT, KP CONAWAY, RC CONAWAY, JW LINEHAN, WM KLAUSNER, RD TI INHIBITION OF TRANSCRIPTION ELONGATION BY THE VHL TUMOR-SUPPRESSOR PROTEIN SO SCIENCE LA English DT Article ID FACTOR-SIII; IDENTIFICATION AB Germline mutations in the von Hippel-Lindau tumor suppressor gene (VHL) predispose individuals to a variety of tumors, including renal carcinoma, hemangioblastoma of the central nervous system, and pheochromocytoma. Here, a cellular transcription factor, Elongin (SIII), is identified as a functional target of the VHL protein. Elongin (SIII) is a heterotrimer consisting of a transcriptionally active subunit (A) and two regulatory subunits (B and C) that activate transcription elongation by RNA polymerase II. The VHL protein was shown to bind tightly and specifically to the Elongin B and C subunits and to inhibit Elongin (SIII) transcriptional activity in vitro. These findings reveal a potentially important transcriptional regulatory network in which the VHL protein may play a key role. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. NCI,SURG BRANCH,UROL ONCOL SECT,BETHESDA,MD 20892. AMER RED CROSS,JEROME H HOLLAND LAB,DEPT BIOL MOLEC,ROCKVILLE,MD 20855. OKLAHOMA MED RES FDN,PROGRAM MOLEC BIOL,OKLAHOMA CITY,OK 73104. OI Conaway, Joan/0000-0002-2786-0663 FU NIGMS NIH HHS [GM41628] NR 26 TC 443 Z9 453 U1 0 U2 3 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD SEP 8 PY 1995 VL 269 IS 5229 BP 1402 EP 1406 DI 10.1126/science.7660122 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RT806 UT WOS:A1995RT80600038 PM 7660122 ER PT J AU ASZALOS, A PINE, PS PANDEY, R GOTTESMAN, MM AF ASZALOS, A PINE, PS PANDEY, R GOTTESMAN, MM TI BEHAVIOR OF N-ACYLATED DAUNORUBICINS IN MDR1 GENE TRANSFECTED AND PARENTAL CELLS SO BIOCHEMICAL PHARMACOLOGY LA English DT Note DE MULTIDRUG RESISTANT CANCER CELLS; N-ACYL-DAUNORUBICINS; CELL PROLIFERATION; FLUORESCENCE; CONFOCAL MICROSCOPY ID EHRLICH ASCITES TUMOR; MULTIDRUG-RESISTANT CELLS; DRUG-RESISTANCE; TRANSPORTER; DOXORUBICIN AB The substrate specificity of the P-glycoprotein (P-170), a multidrug transporter, was studied using N-acylated daunorubicin derivatives and four MDR1 cDNA transfected cell lines. Results showed that N-acetyl-daunorubicin is a substrate, but the longer fatty acid derivatives, N-octanoyl and N-dodecanoyl daunorubicins, are not. This conclusion was reached by flow cytometric drug uptake assay, cell proliferation assays, and confocal microscopy. It was concluded that the longer fatty acid derivatives interact with plasma membranes in a way that affected P-glycoprotein function. C1 XECHEM INC,NEW BRUNSWICK,NJ. NCI,CELL BIOL LAB,BETHESDA,MD 20892. RP ASZALOS, A (reprint author), US FDA,DIV RES & TESTING,200 C ST SW,WASHINGTON,DC 20204, USA. NR 16 TC 8 Z9 8 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD SEP 7 PY 1995 VL 50 IS 6 BP 889 EP 892 DI 10.1016/0006-2952(95)00209-I PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RW999 UT WOS:A1995RW99900022 PM 7575653 ER PT J AU SHEARER, GM AF SHEARER, GM TI PHARMACOLOGY - REDIRECTING T-CELL FUNCTION SO NATURE LA English DT Editorial Material RP SHEARER, GM (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 10 TC 5 Z9 5 U1 0 U2 1 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD SEP 7 PY 1995 VL 377 IS 6544 BP 16 EP 17 DI 10.1038/377016a0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RT725 UT WOS:A1995RT72500030 PM 7659150 ER PT J AU RABKIN, CS CHIBWE, G MUYUNDA, K MUSABA, E AF RABKIN, CS CHIBWE, G MUYUNDA, K MUSABA, E TI KAPOSIS-SARCOMA IN PREGNANT-WOMEN SO NATURE LA English DT Letter C1 UNIV LUSAKA,TEACHING HOSP,DERMATOVENEROL CLIN,LUSAKA,ZAMBIA. RP RABKIN, CS (reprint author), NCI,VIRAL EPIDEMIOL BRANCH,EPN 434,BETHESDA,MD 20892, USA. NR 3 TC 24 Z9 25 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD SEP 7 PY 1995 VL 377 IS 6544 BP 21 EP 21 DI 10.1038/377021a0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RT725 UT WOS:A1995RT72500036 PM 7659154 ER PT J AU LUNARDIISKANDAR, Y ZEMAN, RA LAM, VH SAMANIEGO, F THIERRY, AR GALLO, RC BRYANT, JL BESNIER, JM HERMANS, P GILL, P AF LUNARDIISKANDAR, Y ZEMAN, RA LAM, VH SAMANIEGO, F THIERRY, AR GALLO, RC BRYANT, JL BESNIER, JM HERMANS, P GILL, P TI KAPOSIS-SARCOMA IN PREGNANT-WOMEN - REPLY SO NATURE LA English DT Letter C1 NIDR,ANIM CARE UNIT,BETHESDA,MD 20892. GYNECOL & OBSTET MED CTR,F-75017 PARIS,FRANCE. FREE UNIV BRUSSELS,HOP ST PIERRE,DEPT MALAD INFECT,B-1000 BRUSSELS,BELGIUM. UNIV SO CALIF,SCH MED,LOS ANGELES,CA 90033. RP LUNARDIISKANDAR, Y (reprint author), NCI,TUMOR CELL BIOL LAB,BLDG 37,BETHESDA,MD 20892, USA. RI thierry, alain/F-9492-2014 NR 10 TC 4 Z9 4 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD SEP 7 PY 1995 VL 377 IS 6544 BP 22 EP 22 DI 10.1038/377022a0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RT725 UT WOS:A1995RT72500038 ER PT J AU MACCHI, P VILLA, A GILIANI, S SACCO, MG FRATTINI, A PORTA, F UGAZIO, AG JOHNSTON, JA CANDOTTI, F O'SHEA, JJ VEZZONI, P NOTARANGELO, LD AF MACCHI, P VILLA, A GILIANI, S SACCO, MG FRATTINI, A PORTA, F UGAZIO, AG JOHNSTON, JA CANDOTTI, F O'SHEA, JJ VEZZONI, P NOTARANGELO, LD TI MUTATIONS OF JAK-3 GENE IN PATIENTS WITH AUTOSOMAL SEVERE COMBINED IMMUNE-DEFICIENCY (SCID) SO NATURE LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; X-CHROMOSOME INACTIVATION; CARRIERS; CELLS AB SEVERE combined immune deficiency (SCID) represents a heterogenous group of hereditary diseases. Mutations in the common gamma-chain (gamma(c)), which is part of several cytokine receptors including those for interleukin (IL)-2, IL-4, IL-7, IL-9 and IL-15, are responsible for X-linked SCID1,2, which is usually(!ly associated with a lack of circulating T cells and the presence of B lymphocytes (T- B+ SCID), The gene(s) responsible for autosomal recessive T- B+ SCID is still unknown, The Jak-3 protein kinase(3,4) has been found to associate,vith the gamma(c)-chain-containing cytokine receptors(4-9). Therefore Jak-3 or other STAT proteins with which it interacts(10,11) are candidate genes for autosomal recessive T- B+ SCID7. Here we investigate two unrelated T- B+ SCID patients (both from consanguineous parents) who have homozygous mutations in the gene for Jak-3. One patient carries a mutation (Tyr100-->Cys) in a conserved tyrosine residue in the JH7 domain of Jak-3 which is absent in more than 150 investigated chromosomes. The other patient carries a homozygous 151-base-pair deletion in the kinase-like domain, leading to a frameshift and premature termination. Both mutations resulted in markedly reduced levels of Jak-3, These findings show that abnormalities in the Jak/STAT signalling pathway can account for SCID in humans. C1 CNR, IST TECNOL BIOMED AVANZATE, I-20131 MILAN, ITALY. UNIV BRESCIA, DIPARTIMENTO MATERNO INFANTILE, BRESCIA, ITALY. NIH, NATL CTR HUMAN GENOME RES, CLIN GENE THERAPY BRANCH, BETHESDA, MD 20892 USA. RI Notarangelo, Luigi/F-9718-2016; OI Notarangelo, Luigi/0000-0002-8335-0262; Villa, Anna/0000-0003-4428-9013 NR 19 TC 559 Z9 573 U1 2 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 7 PY 1995 VL 377 IS 6544 BP 65 EP 68 DI 10.1038/377065a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RT725 UT WOS:A1995RT72500057 PM 7659163 ER PT J AU BOGUSKI, MS AF BOGUSKI, MS TI HUNTING FOR GENES IN COMPUTER-DATA BASES SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article RP BOGUSKI, MS (reprint author), NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 4 TC 11 Z9 11 U1 0 U2 2 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 7 PY 1995 VL 333 IS 10 BP 645 EP 647 DI 10.1056/NEJM199509073331008 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA RR840 UT WOS:A1995RR84000008 PM 7637727 ER PT J AU LOCKSHIN, MD AF LOCKSHIN, MD TI THROMBOSIS IN THE ANTIPHOSPHOLIPID-ANTIBODY SYNDROME SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP LOCKSHIN, MD (reprint author), NIAMSD,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 7 PY 1995 VL 333 IS 10 BP 667 EP 667 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA RR840 UT WOS:A1995RR84000022 PM 7637739 ER PT J AU PELICCI, G LANFRANCONE, L SALCINI, AE ROMANO, A MELE, S BORRELLO, MG SEGATTO, O DIFIORE, PP PELICCI, PG AF PELICCI, G LANFRANCONE, L SALCINI, AE ROMANO, A MELE, S BORRELLO, MG SEGATTO, O DIFIORE, PP PELICCI, PG TI CONSTITUTIVE PHOSPHORYLATION OF SHC PROTEINS IN HUMAN TUMORS SO ONCOGENE LA English DT Article DE SHC PHOSPHORYLATION; HUMAN TUMORS ID GUANINE-NUCLEOTIDE EXCHANGE; GROWTH-FACTOR RECEPTOR; TYROSINE KINASE; SIGNAL TRANSDUCTION; ADAPTER PROTEIN; SEVENLESS GENE; V-SRC; RAS; GRB2; IDENTIFICATION AB The She gene encodes three overlapping proteins which all contain a carboxy-terminal SH2 domain. She proteins are ubiquitously expressed and are downstream targets and effecters of activated tyrosine kinases (TK). We investigated tyrosine-phosphorylation of She proteins in normal and transformed cells. In tumor cells with known TK gene alterations She proteins were constitutively phosphorylated and complexed with the activated TK. No constitutive She phosphorylation was found in primary cell cultures and normal tissues, In 14 of 27 tumor cell lines with no reported TK alterations, She proteins were constitutively phosphorylated and formed stable complexes with novel tyrosine-phosphorylated polypeptides. Ten distinct She-associated phosphoproteins were identified with molecular weights ranging from 30 to 200 kDa. In a subset of carcinoma cell lines, phosphorylated She proteins complexed with a p175 phosphoprotein that was identified as the constitutively activated EGFR. In one glioblastoma cell line, a Shc-associated p190 was identified as the activated PDGFR. In 13 of 14 acute leukemia samples phosphorylated She proteins were constitutively complexed with a p140 phosphoprotein. Some of the She-associated phosphoproteins (EGFR, PDGFR, erbB-2, Met, bcr-abl, H4-ret) bound both the Shc- and Grb2-SH2 domains in vitro; others (p175; p70-p80) only the Shc-SH2 domain and yet others (p140) only the Grb2-SH3 domains. These results indicate that She proteins are common substrates of constitutively activated TKs and that the analysis of She phosphorylation allow the identification of tumors with constitutive TK activation. C1 UNIV PERUGIA,IST MED INTERNA & SCI ONCOL,I-06100 PERUGIA,ITALY. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. IST NAZL TUMORI,MILAN,ITALY. IST REGINA ELENA,ROME,ITALY. FAC MED & CHIRURG BARI,IST MICROBIOL,BARI,ITALY. EUROPEAN INST ONCOL,MILAN,ITALY. RI Di Fiore, Pier Paolo/K-2130-2012; Borrello, Maria Grazia/C-3161-2017 OI Di Fiore, Pier Paolo/0000-0002-2252-0950; Borrello, Maria Grazia/0000-0002-6854-2848 NR 50 TC 115 Z9 116 U1 1 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 7 PY 1995 VL 11 IS 5 BP 899 EP 907 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA RU798 UT WOS:A1995RU79800011 PM 7675449 ER PT J AU BLAGOSKLONNY, MV TORETSKY, J NECKERS, L AF BLAGOSKLONNY, MV TORETSKY, J NECKERS, L TI GELDANAMYCIN SELECTIVELY DESTABILIZES AND CONFORMATIONALLY ALTERS MUTATED P53 SO ONCOGENE LA English DT Article DE BENZOQUINONE ANSAMYCINS; GELDANAMYCIN; MUTATED P53; PROTEIN STABILITY ID TUMOR-SUPPRESSOR PROTEIN; CANCER CELL-LINES; MUTANT P53; ACTIVATING MUTATIONS; BINDING-SITE; DNA-DAMAGE; COS CELLS; WILD-TYPE; GENE; TRANSFORMATION AB Mutated p53 proteins interfere in the function of wild type p53 and may also serve as a dominant oncogene, The vast majority of p53 mutations result in a protein of altered conformation and prolonged half-life. We sought to examine whether geldanamycin, a drug capable of destabilizing several oncogene and proto-oncogene products, could alter the stability and DNA binding characteristics of several mutated p53 proteins, Brief exposure to GA destabilized the p53 protein of several breast, prostate and leukemic cell lines harboring mutated p53 alleles, resulting in a significant reduction in p53 steady state level and half-life. In contrast to its effects on mutated p53, GA altered neither steady state level nor inducibility of the wild type protein. In addition to its effects on protein stability, GA also altered the conformation of mutated p53, so that it was no longer detectable with a mutant conformation-specific antibody. Finally, mutated p53 protein isolated from GA-treated cells regained partial ability to bind a wild type-specific p53 DNA consensus sequence, These data indicate the feasability of pharmacologic intervention for altering the mutated p53 phenotype. C1 NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NR 52 TC 161 Z9 161 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 7 PY 1995 VL 11 IS 5 BP 933 EP 939 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA RU798 UT WOS:A1995RU79800014 PM 7675452 ER PT J AU SANG, QX BIRKEDALHANSEN, H VANWART, HE AF SANG, QX BIRKEDALHANSEN, H VANWART, HE TI PROTEOLYTIC AND NONPROTEOLYTIC ACTIVATION OF HUMAN NEUTROPHIL PROGELATINASE-B SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY LA English DT Article DE GELATINASE B; MATRILYSIN; COLLAGENASE; ZYMOGEN ACTIVATION; HUMAN MATRIX METALLOPROTEINASE ID HUMAN FIBROBLAST COLLAGENASE; HUMAN MONONUCLEAR PHAGOCYTES; GELATIN-SPECIFIC PROTEINASE; IV COLLAGENASE; MATRIX METALLOPROTEINASE-9; INTERSTITIAL COLLAGENASE; ENDOGENOUS ACTIVATION; LATENT COLLAGENASE; FIBROSARCOMA CELLS; HUMAN MACROPHAGES AB The activation of human neutrophil progelatinase B (pro-HNG) by a variety of proteolytic and non-proteolytic activators has been investigated. A quantitative comparison of the activation efficiencies of treatments previously reported to activate pro-HNG or the related gelatinase B species produced by other cells demonstrates that stromelysin and trypsin are good activators. HgCl2 is a moderately effective activator, while p-chloromercuribenzoate and NaOCl are poor activators. It is also shown that human matrilysin and human fibroblast-type collagenase can activate pro-HNG by a mechanism that is very similar to that of stromelysin. Initially, these proteinases hydrolyze the Glu(40)-Met(41) bond in the propeptide domain to generate an 88 kDa inactive HNG species. Collagenase also generates a 68 kDa HNG species through hydrolysis of the Ala(74)-Met(75) bond. Ultimately, treatment with either matrilysin, collagenase or trypsin results in the production of a 65 kDa active form of HNG that arises from hydrolysis of the Ag-87-Phe(88) bond, This is the same active species produced on activation by stromelysin. This cleavage site is downstream of the 'cysteine-switch' residue located at position 80 and releases it, accounting for the permanent activation of the enzyme. These results suggest that matrilysin and collagenase may be physiologically relevant activators of pro-HNG and/or other progelatinase B species. Activation by HgCl2 produces an active 68 kDa enzyme due to autolytic hydrolysis of the Ala(74)-Met(75) bond. This species retains the cysteine switch residue; however, it is shown that it is only active in the continued presence of HgCl2. Removal of the HgCl2 restores latency, indicating that this species is reversibly activated by HgCl2, which functions by complexing the sulfhydryl group of the cysteine switch residue and keeping it dissociated from the active site zinc atom. Thus, in spite of reports to the contrary, the cysteine switch mechanism can account for the latency and activation of pro-HNG. C1 SYNTEX INC,DISCOVERY RES,INST BIOCHEM & CELL BIOL,PALO ALTO,CA 94304. NIDR,BETHESDA,MD 20892. FLORIDA STATE UNIV,DEPT CHEM,TALLAHASSEE,FL 32306. FLORIDA STATE UNIV,INST MOLEC BIOPHYS,TALLAHASSEE,FL 32306. FU NIDCR NIH HHS [DE08228]; NIGMS NIH HHS [GM46051, F32 GM14336] NR 53 TC 84 Z9 86 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4838 J9 BBA-PROTEIN STRUCT M JI Biochim. Biophys. Acta-Protein Struct. Molec. Enzym. PD SEP 6 PY 1995 VL 1251 IS 2 BP 99 EP 108 DI 10.1016/0167-4838(95)00086-A PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RU443 UT WOS:A1995RU44300004 PM 7669817 ER PT J AU HORNUNG, RL LONGO, DI BOWERSOX, OC KWAK, LW AF HORNUNG, RL LONGO, DI BOWERSOX, OC KWAK, LW TI TUMOR ANTIGEN-SPECIFIC IMMUNIZATION OF BONE-MARROW TRANSPLANTATION DONORS AS ADOPTIVE THERAPY AGAINST ESTABLISHED TUMOR SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID T-CELL IMMUNITY; NON-HODGKINS LYMPHOMA; PROTEIN; RECIPIENT; RECOGNIZE; RESPONSES; PEPTIDES; RAS AB Background: Persistence of the underlying malignancy remains the main obstacle to the successful treatment of human malignancies with high-dose chemoradiotherapy and bone marrow transplantation. Purpose: The aim of this study was to determine whether antigen-specific antitumor immune responses, elicited in normal donor mice by immunization,vith the soluble form of a surrogate tumor antigen (i.e., ovalbumin [OVA]), can be transferred via bone marrow transplantation into lethally irradiated, syngeneic recipient mice, An additional goal was to evaluate the ability of these adoptively transferred bone marrow cells to eradicate established recombinant OVA-expressing lymphomas that recurred after lethal-dose total-body irradiation (TBI), Methods: Female C57BL/6 donor mice were immunized twice with OVA emulsified in a muramyl-dipeptide-containing adjuvant, Syngeneic mice bearing a day-10 or day-ii, approximately l-cm subcutaneous E,G7-OVA tumor (E.G7-OVA tumor cells were derived from transfection of EL-4 thymoma tumor cells using the coding sequence of chicken OVA gene complementary DNA) were treated with TBI and reconstituted with bone marrow from nonimmune or OVA-immunized mice, In subsequent experiments, tumor-bearing mice, treated with TBI and OVA-immune bone marrow, were given additional therapy either with a single OVA immunization or by the adoptive transfer of 1 x 10(7) in vitro activated spleen cells derived from OVA-immune donor mice and cultured 5 days with irradiated E,G7-OVA cells before transfer, Results: E,G7-OVA tumor-bearing mice given TBI and OVA-immune bone marrow showed a significantly increased cure rate when compared with that among controls reconstituted with nonimmune bone marrow after TBI (logrank, P<.01), The antitumor effect of immune bone marrow was abrogated by T-cell depletion of the marrow graft (P<.016). The antitumor effect of immune marrow was enhanced by the addition of OVA immunization of tumor-bearing recipients (P<.015). OVA-specific cytotoxic T-lymphocyte (CTL) activity was recovered from tumor-bearing recipients of immune marrow 14 days after bone marrow transplantation. The antitumor effect observed following the adoptive transfer of immune marrow was further augmented by the addition of 1 x 10(7) splenic E.G7-OVA-specific in vitro activated CTLs derived from OVA-immune mice (P<.03), Conclusion: These studies establish the principle that antigen-specific T-cell immunity against a defined tumor-specific antigen can be transferred with bone marrow from an immune donor, Implications: Active immunization of normal human bone marrow or T-cell donors with a refined, safe tumor antigen and transfer of immunity to the patient may represent a novel strategy for circumventing the obstacle of host immune suppression associated with the tumor-bearing state. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,DIV CANC TREATMENT,FREDERICK,MD 21702. SAIC FREDERICK,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NR 32 TC 23 Z9 24 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 6 PY 1995 VL 87 IS 17 BP 1289 EP 1296 DI 10.1093/jnci/87.17.1289 PG 8 WC Oncology SC Oncology GA RR583 UT WOS:A1995RR58300010 PM 7544833 ER PT J AU SEIDMAN, AD PORTENOY, R YAO, TJ LEPORE, J MONT, EK KORTMANSKY, J ONETTO, N REN, L GRECHKO, J BELTANGADY, M USAKEWICZ, J SOUHRADA, M HOUSTON, C MCCABE, M SALVAGGIO, R THALER, H NORTON, L AF SEIDMAN, AD PORTENOY, R YAO, TJ LEPORE, J MONT, EK KORTMANSKY, J ONETTO, N REN, L GRECHKO, J BELTANGADY, M USAKEWICZ, J SOUHRADA, M HOUSTON, C MCCABE, M SALVAGGIO, R THALER, H NORTON, L TI QUALITY-OF-LIFE IN PHASE-II TRIALS - A STUDY OF METHODOLOGY AND PREDICTIVE VALUE IN PATIENTS WITH ADVANCED BREAST-CANCER TREATED WITH PACLITAXEL PLUS GRANULOCYTE-COLONY-STIMULATING FACTOR SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID FUNCTIONAL LIVING INDEX; CLINICAL-TRIALS; QUESTIONNAIRE; CHEMOTHERAPY; PAIN AB Background: Despite the clinical benefit that may be associated with reduction of tumor volume, chemotherapy may produce physical or psychological distress that could compromise a patient's quality of life, Although palliation may be as relevant as tumor response in patients with metastatic breast cancer, quality of life is not commonly evaluated in phase II clinical trials of new therapeutic agents. Purpose: We evaluated the utility of quality-of-life assessment in two phase II clinical trials of patients receiving paclitaxel (Taxol) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) as salvage therapy for metastatic breast cancer, Methods: A battery of instruments (i,e,, Memorial Symptom Assessment Scale [MSAS], Functional Living Index-Cancer [FLIC], Rand Mental Health Inventory [MHI], Brief Pain Inventory [BPI], and Memorial Pain Assessment Card [MPAC]) designed to capture information about social, psychological, and functional aspects of quality of life, as well as symptom prevalence and distress, was completed prior to treatment; serial assessments were obtained at regular intervals during the treatment period, Univariate and multivariate analyses were performed evaluating base-line quality-of-life parameters and standard prognostic factors in relation to outcome measures of survival, tumor response, and toxicity, For 30 consecutive patients with extensive prior chemotherapy for metastatic disease, longitudinal data were analyzed associating tumor response to changes in quality-of-life scores throughout the course of treatment with paclitaxel. Results: Base-line scores of two validated quality-of-life instruments, the MSAS and the FLIC, independently predicted the overall survival (P<.01 for each), In this model, however, neither standard prognostic factors nor quality of life instruments predicted the likelihood of tumor response or the probability of encountering grade 3 or grade 4 nonhematologic toxicity, With serial assessments of quality of life, the majority of patients who achieved partial tumor response or stable disease reported improved or unchanged quality-of-life scores, while those patients with progressive disease experienced rapid deterioration in quality of life, Conclusions: Base-line quality-of-life assessment may provide prognostic information distinct from that obtained through standard prognostic indicators alone, The combination of two factors-extent of disease and a base-line quality-of-life assessment-predicted survival more accurately than either used separately. Evaluation of quality-of-life outcomes in relation to tumor response mag illuminate previously unmeasured palliative effects of chemotherapy, such as pain relief, as well as the burdens it imposes, Implications: Information obtained from quality-of-life assessment in conjunction with phase II testing of new chemotherapeutic agents for metastatic breast cancer can guide quality-of-life evaluation planned in large, randomized future studies. C1 MEM SLOAN KETTERING CANC CTR,DEPT BIOSTAT & EPIDEMIOL,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,DEPT NURSING,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,DEPT NEUROL,NEW YORK,NY 10021. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,WALLINGFORD,CT. NCI,DIV CANC TREATMENT,CANC TREATMENT EVALUAT PROGRAM,BETHESDA,MD 20892. RP SEIDMAN, AD (reprint author), MEM SLOAN KETTERING CANC CTR,DEPT MED,DIV SOLID TUMOR ONCOL,BREAST & GYNECOL CANC MED SERV,NEW YORK,NY 10021, USA. FU NCI NIH HHS [CA0920714, 1CM07311] NR 26 TC 74 Z9 76 U1 0 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 6 PY 1995 VL 87 IS 17 BP 1316 EP 1322 DI 10.1093/jnci/87.17.1316 PG 7 WC Oncology SC Oncology GA RR583 UT WOS:A1995RR58300014 PM 7544834 ER PT J AU TRAVIS, LB CURTIS, RE BENNETT, WP HANKEY, BF TRAVIS, WD BOICE, JD AF TRAVIS, LB CURTIS, RE BENNETT, WP HANKEY, BF TRAVIS, WD BOICE, JD TI LUNG-CANCER AFTER HODGKINS-DISEASE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Note ID 2ND MALIGNANCIES; LYMPHOMA; RISK C1 NCI,DIV CANC ETIOL,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20892. NCI,DIV CANC ETIOL,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,DIV CANC PREVENT & CONTROL,CANC STAT BRANCH,BETHESDA,MD 20892. ARMED FORCES INST PATHOL,DEPT PULM & MEDIASTINAL PATHOL,WASHINGTON,DC 20306. NR 25 TC 27 Z9 28 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 6 PY 1995 VL 87 IS 17 BP 1324 EP 1327 DI 10.1093/jnci/87.17.1324 PG 4 WC Oncology SC Oncology GA RR583 UT WOS:A1995RR58300016 PM 7658485 ER PT J AU VONLUBITZ, DKJE KIM, J BEENHAKKER, M CARTER, MF LIN, RCS MESHULAM, Y DALY, JW SHI, D ZHOU, LM JACOBSON, KA AF VONLUBITZ, DKJE KIM, J BEENHAKKER, M CARTER, MF LIN, RCS MESHULAM, Y DALY, JW SHI, D ZHOU, LM JACOBSON, KA TI CHRONIC NMDA RECEPTOR STIMULATION - THERAPEUTIC IMPLICATIONS OF ITS EFFECT ON ADENOSINE A(1) RECEPTORS SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE ADENOSINE A(1) RECEPTOR; NMDA RECEPTOR; SEIZURE; ALZHEIMERS DISEASE; (MOUSE) ID EXCITATORY AMINO-ACIDS; RAT CORTICAL SLICES; METHYL-D-ASPARTATE; ALZHEIMERS-DISEASE; ENDOGENOUS ADENOSINE; BRAIN; HIPPOCAMPUS; CHANNELS; RELEASE; DENSITY AB It is known that stimulation of adenosine A(1) receptors has a modulatory effect on the excitability of postsynaptic NMDA receptors. Conversely, acute stimulation of NMDA receptors results in release of adenosine via calcium-independent mechanisms. These findings indicate a close functional relationship between these receptors. It is, therefore, possible that chronic, low level stimulation of the NMDA receptor may have a negative impact on these modulatory processes. To investigate this possibility, we have subjected C57BL mice either to an acute injection of a N-6-cyclopentyladenosine (CPA, 0.01 mg/kg) or deoxycoformycin (1 mg/kg) followed by a convulsant dose of N-methyl-D-aspartate (NMDA) (60 mg/kg) or to chronic, low level (20 mg/kg i.p. daily) exposure to NMDA for 8 weeks. One day after the last injection of NMDA, animals were injected either with a convulsant dose of NMDA alone, or with either CPA at 0.001 or 0.01 mg/kg, or with 1 mg/kg deoxycoformycin followed 15 min later by 60 mg/kg NMDA. Neither CPA nor deoxycoformycin were protective when NMDA was given acutely at 60 mg/kg. Chronic treatment with NMDA alone or chronic administration of NMDA followed by 0.001 mg/kg CPA had no significant effect on mortality following a convulsant dose of NMDA. However, when the chronic regimen of NMDA was followed by either 0.01 mg/kg CPA or 1 mg/kg deoxycoformycin, mortality was reduced to 10% (CPA), or eliminated completely (deoxycoformycin). Moreover, combination of chronic NMDA treatment with either CPA (both doses) or deoxycoformycin produced a significant improvement in other measures, i.e., seizure onset, intensity of neurological impairment, and extension of time to death. Consonant with these results, apparent density of adenosine A(1) receptors was increased in the cortex and hippocampus of animals treated chronically with NMDA. Our results indicate a possible role for NMDA-adenosine A(1) receptor interaction in pathologies in which chronic stimulation of the NMDA receptor by endogenous excitatory amino acids may be involved. C1 HAHNEMANN UNIV,DEPT PHYSIOL & BIOPHYS,PHILADELPHIA,PA 19102. NIDDK,NEUROSCI LAB,BETHESDA,MD 20892. RP VONLUBITZ, DKJE (reprint author), NIDDK,BIOORGAN CHEM LAB,BLDG 8,RM 111,BETHESDA,MD 20892, USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20] NR 35 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD SEP 5 PY 1995 VL 283 IS 1-3 BP 185 EP 192 DI 10.1016/0014-2999(95)00338-L PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RU504 UT WOS:A1995RU50400022 PM 7498308 ER PT J AU ELMER, GI EVANS, JL LADENHEIM, B EPSTEIN, CJ CADET, JL AF ELMER, GI EVANS, JL LADENHEIM, B EPSTEIN, CJ CADET, JL TI TRANSGENIC SUPEROXIDE-DISMUTASE MICE DIFFER IN OPIOID-INDUCED ANALGESIA SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE TRANSGENIC MOUSE; SUPEROXIDE DISMUTASE; OPIATE RECEPTOR; ANTINOCICEPTION; GENETICS ID CENTRAL NERVOUS-SYSTEM; NUCLEUS-ACCUMBENS; RECEPTORS; BINDING; BRAIN; RAT; INHIBITION; ZINC AB Autoradiographic data from transgenic mice carrying the human Cu/Zn-superoxide dismutase gene demonstrate an increase in mu-opioid receptor concentration in dopaminergic-related areas and the central grey area. The relative potencies of mu-, delta- and kappa-opioid receptor agonists to induce antinociception in heterozygous and homozygous superoxide dismutase transgenic mice as well as four inbred strains were assessed to determine the functional significance of the increased receptor concentration. Increased superoxide dismutase activity results in an increased sensitivity to mu-agonists in a gene dosage-dependent manner. SOD/Tg/hom mice were less sensitive to the delta-agonist than were SOD/Tg/het mice. The superoxide dismutase transgene did not affect kappa-opioid receptor agonist sensitivity. These data suggest that delta-opioid receptors are not regulated in the same manner as mu-opioid receptors and that kappa-opioid receptors are unaffected by superoxide dismutase activity. C1 NIDA,DIV INTRAMURAL RES,MOLEC NEUROPSYCHIAT SECT,BALTIMORE,MD 21224. UNIV CALIF SAN FRANCISCO,DEPT PEDIAT,SAN FRANCISCO,CA 94143. RP ELMER, GI (reprint author), NIDA,DIV INTRAMURAL RES,BEHAV PHARMACOL & GENET SECT,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. FU NIA NIH HHS [AG-08938] NR 27 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD SEP 5 PY 1995 VL 283 IS 1-3 BP 227 EP 232 DI 10.1016/0014-2999(95)00365-R PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RU504 UT WOS:A1995RU50400027 PM 7498314 ER PT J AU MCCANN, UD YUAN, J RICAURTE, GA AF MCCANN, UD YUAN, J RICAURTE, GA TI FENFLURAMINES APPETITE SUPPRESSION AND SEROTONIN NEUROTOXICITY ARE SEPARABLE SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Note DE FENFLURAMINE; NEUROTOXICITY; APPETITE ID NONHUMAN-PRIMATES; NEURONS; MDMA AB To determine whether fenfluramine's anorectic and neurotoxic effects could be dissociated, rats were treated with fenfluramine or the serotonin transporter blocker fluoxetine, alone or in combination. Fenfluramine alone produced anorexia, weight loss and lasting depletions of brain serotonin axon markers. Fluoxetine prevented fenfluramine-induced long-term serotonergic deficits, yet did not diminish fenfluramine's acute anorectic effects. These findings indicate that fenfluramine's anorectic and neurotoxic actions are distinct and separable. C1 NIMH,BIOL PSYCHIAT BRANCH,ANXIETY & AFFECT DISORDERS SECT,BETHESDA,MD 20892. JOHNS HOPKINS MED INST,DEPT NEUROL,BALTIMORE,MD 21224. FU NIDA NIH HHS [KO2 DA00206, R01 DA06275] NR 8 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD SEP 5 PY 1995 VL 283 IS 1-3 BP R5 EP R7 DI 10.1016/0014-2999(95)00482-Z PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RU504 UT WOS:A1995RU50400033 PM 7498296 ER PT J AU LIAW, KL HSING, AW CHEN, CJ SCHIFFMAN, MH ZHANG, TY HSIEH, CY GREER, CE YOU, SL HUANG, TW WU, TC OLEARY, TJ SEIDMAN, JD BLOT, WJ MEINERT, CL MANOS, MM AF LIAW, KL HSING, AW CHEN, CJ SCHIFFMAN, MH ZHANG, TY HSIEH, CY GREER, CE YOU, SL HUANG, TW WU, TC OLEARY, TJ SEIDMAN, JD BLOT, WJ MEINERT, CL MANOS, MM TI HUMAN PAPILLOMAVIRUS AND CERVICAL NEOPLASIA - A CASE-CONTROL STUDY IN TAIWAN SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID INTRAEPITHELIAL NEOPLASIA; RISK-FACTORS; INFECTION; CARCINOMA; COLOMBIA; CANCER; SPAIN; CHINA AB As part of a large-scale, community-based cervical neoplasia screening project in rural Taiwan, a case-control study was undertaken to evaluate the etiologic role of human papillomavirus (HPV) infection in this mainly monogamous (2% reported having multiple sexual partners) female population. A total of 88 biopsy-confirmed cases and 261 cytologically normal controls were selected for the study. The case group included 40 cases of cervical intraepithelial neoplasia (CIN) 1, 9 of CIN 2, 36 of CIN 3 and 3 cases of invasive cancer. Cervical swabs collected at screening from study subjects were tested for HPV DNA by an L1 consensus primer polymerase chain reaction (PCR)-based technique. HPV DNA was found in 92% of high-grade cases (GIN 2-3 and invasive cancer); 54% of low-grade cases (CIN 1); and 9% of controls. HPV was significantly associated with both high-grade and low-grade cervical neoplasia As reported in Western countries, HPV 16 was the predominant type among HPV-positive high-grade cases. However, HPVs 52 and/or 58 combined were the most common types among HPV-positive low-grade cases and controls. Among women without any high-risk HPV infection (types 16, 18, 31 or 45), those with multiple-type HPV infection had a higher risk for high-grade cervical neoplasia than those with single-type infection. Overall, 91% of high-grade cases and 50% of low-grade cases could be attributed to HPV infection. Our results show that, even in this monogamous population, HPV is the major risk factor for high-grade cervical neoplasia. (C) 1995 Wiley-Liss, Inc. C1 JOHNS HOPKINS UNIV,BALTIMORE,MD. NATL TAIWAN UNIV,TAIPEI,TAIWAN. ROCHE MOLEC SYST,ALAMEDA,CA. CHIRON CORP,EMERYVILLE,CA 94608. TAIPEI INST PATHOL,TAIPEI,TAIWAN. USAF,INST PATHOL,WASHINGTON,DC. RP LIAW, KL (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,6130 EXECUT BLVD,ROOM 415,BETHESDA,MD 20892, USA. RI Chen, Chien-Jen/C-6976-2008 NR 30 TC 76 Z9 80 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 4 PY 1995 VL 62 IS 5 BP 565 EP 571 DI 10.1002/ijc.2910620513 PG 7 WC Oncology SC Oncology GA RT089 UT WOS:A1995RT08900012 PM 7665227 ER PT J AU BALABAN, RS AF BALABAN, RS TI NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY SO ACADEMIC RADIOLOGY LA English DT Article; Proceedings Paper CT Conference on Developing a Long-Term Plan for Imaging Research CY NOV 05-08, 1994 CL BETHESDA, MD SP NIH, NCI RP BALABAN, RS (reprint author), NHLBI,BLDG 10,RM BID-161,BETHESDA,MD 20892, USA. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD SEP PY 1995 VL 2 SU 2 BP S136 EP S137 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RT158 UT WOS:A1995RT15800023 PM 9419726 ER PT J AU BAUM, S ECKELMAN, WC GARCIA, EV HOLMAN, BL KUNG, HF MATTREY, RF PIWNICAWORMS, D WAHL, RL WATSON, JT AF BAUM, S ECKELMAN, WC GARCIA, EV HOLMAN, BL KUNG, HF MATTREY, RF PIWNICAWORMS, D WAHL, RL WATSON, JT TI CONTRAST-MEDIA AND RADIOPHARMACEUTICAL AGENTS - REGULATORY ISSUES SO ACADEMIC RADIOLOGY LA English DT Article; Proceedings Paper CT Conference on Developing a Long-Term Plan for Imaging Research CY NOV 05-08, 1994 CL BETHESDA, MD SP NIH, NCI C1 UNIV CALIF SAN DIEGO,SAN DIEGO MED CTR,DEPT RADIOL,SAN DIEGO,CA 92103. HOSP UNIV PENN,DEPT RADIOL,PHILADELPHIA,PA 19104. HOSP UNIV PENN,DEPT RADIOPHARMACEUT SCI,PHILADELPHIA,PA 19104. NIH,DEPT PET,BETHESDA,MD 20892. EMORY UNIV HOSP,EMORY CTR PET,ATLANTA,GA 30322. BRIGHAM & WOMENS HOSP,DEPT RADIOL,BOSTON,MA 02115. MALLINCKRODT INST RADIOL,DIV RADIAT SCI,ST LOUIS,MO. UNIV MICHIGAN,MED CTR,DIV NUCL MED,ANN ARBOR,MI 48109. NHLBI,DIV HEART & VASC DIS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD SEP PY 1995 VL 2 SU 2 BP S92 EP S93 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RT158 UT WOS:A1995RT15800004 PM 9419707 ER PT J AU ECKELMAN, WC AF ECKELMAN, WC TI POSITRON EMISSION TOMOGRAPHY - RADIOCHEMISTRY SO ACADEMIC RADIOLOGY LA English DT Article; Proceedings Paper CT Conference on Developing a Long-Term Plan for Imaging Research CY NOV 05-08, 1994 CL BETHESDA, MD SP NIH, NCI ID QUANTITATION; INFUSION; BOLUS RP ECKELMAN, WC (reprint author), NIH,BLDG 10,1C401,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD SEP PY 1995 VL 2 SU 2 BP S96 EP S97 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RT158 UT WOS:A1995RT15800006 PM 9419709 ER PT J AU ANDERSEN, OK GRACELY, RH ARENDTNIELSEN, L AF ANDERSEN, OK GRACELY, RH ARENDTNIELSEN, L TI FACILITATION OF THE HUMAN NOCICEPTIVE REFLEX BY STIMULATION OF ALPHA-BETA-FIBERS IN A SECONDARY HYPERALGESIC AREA SUSTAINED BY NOCICEPTIVE INPUT FROM THE PRIMARY HYPERALGESIC AREA SO ACTA PHYSIOLOGICA SCANDINAVICA LA English DT Article DE CAPSAICIN; HYPERALGESIA; NOCICEPTION; REFLEX; SUMMATION ID NEUROGENIC HYPERALGESIA; MECHANICAL HYPERALGESIA; INTRADERMAL INJECTION; FLEXION REFLEX; AFFERENT-FIBERS; FLEXOR REFLEX; CAPSAICIN; PAIN; RAT; EXCITABILITY AB Hyperalgesia was induced in healthy volunteers by topical capsaicin applied on the dorsum of the foot within the receptive field of the sural nerve. Under presence of hyperalgesia different normally non-noxious conditioning stimuli were applied to the hyperalgesic area and the polysynaptic nociceptive spinal reflex and pain ratings were used to assess central excitability. The nociceptive reflex was measured in the knee extensor and flexor muscles evoked by electrical stimulation of the sural nerve trunk at an intensity of 1.5 times the initial reflex threshold (an intensity above the pain threshold). Thermal stimulation of the primary hyperalgesic area (re)established both on-going spontaneous pain and secondary hyperalgesia. Thus, increased nociceptive reflexes were recorded and increased pain intensity reported when A beta-fibres in the secondary hyperalgesic area were activated concurrently with the reflex testing after a non-noxious thermal stimulation of the primary hyperalgesic area. The A beta-fibre activation was achieved by continuous low-intensity electrical stimulation (40 Hz) that was initiated after on-going pain produced by the thermal stimulation had waned. The same measurement without prior thermal conditioning stimulation of the primary area resulted in no reflex facilitation, indicating rapid changes in the central excitability with existence of on-going nociceptive activity. This indicates that the development and maintenance of secondary hyperalgesia are dependent on sustained peripheral nociceptive activity. The study also shows that a central summation of nociceptive and non-nociceptive afferent activity can occur once secondary hyperalgesia is present. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. RP ANDERSEN, OK (reprint author), AALBORG UNIV,CTR SENSORY MOTOR INTERACT,EXPTL PAIN RES LAB,FREDERIK BAJERS VEJ 7D,DK-9220 AALBORG,DENMARK. RI Andersen, Ole Kaseler/J-7825-2013 OI Andersen, Ole Kaseler/0000-0001-6307-8786 NR 30 TC 50 Z9 52 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0001-6772 J9 ACTA PHYSIOL SCAND JI Acta Physiol. Scand. PD SEP PY 1995 VL 155 IS 1 BP 87 EP 97 DI 10.1111/j.1748-1716.1995.tb09951.x PG 11 WC Physiology SC Physiology GA RV284 UT WOS:A1995RV28400011 PM 8553881 ER PT B AU Auerbach, JD AF Auerbach, JD TI In the shadow of the epidemic: Being HIV-negative in the age of AIDS - Odets,W SO AIDS & PUBLIC POLICY JOURNAL LA English DT Book Review RP Auerbach, JD (reprint author), NIH,OFF AIDS RES,BLDG 10,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU UNIV PUBL GROUP, INC PI FREDERICK PA 12 SOUTH MARKET ST, STE 301, FREDERICK, MD 21701 J9 AIDS PUBLIC POLICY J JI Aids Public Policy J. PD FAL PY 1995 VL 10 IS 3 BP 164 EP 167 PG 4 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA UA387 UT WOS:A1995UA38700005 ER PT J AU OTT, DE COREN, LV JOHNSON, DG SOWDER, RC ARTHUR, LO HENDERSON, LE AF OTT, DE COREN, LV JOHNSON, DG SOWDER, RC ARTHUR, LO HENDERSON, LE TI ANALYSIS AND LOCALIZATION OF CYCLOPHILIN-A FOUND IN THE VIRIONS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 MN STRAIN SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID GAG PROTEINS; RETROVIRUSES; HIV-1; ZINC AB Previous reports have shown that cyclophilin A (CyPA) is found to be specifically associated with human immunodeficiency virus type-1 (HIV-1) virions and is required for infectivity (Franke et al. Nature 372:359; Thali et al, Nature 372:363). We have examined CyPA associated with HIV-1(MN) virions, Virions from infected human lymphoid cells were analyzed by high-pressure liquid chromatography (HPLC), protein sequence, and immunoblot analysis. At least three forms of CyPA were found: an unmodified form, an N-terminally modified form, and an N-terminally modified form that migrates as a larger isoform on a reducing-SDS polyacrylamide gel, Using a protease digestion procedure, CyPA that is associated with virions was found to be located inside the viral membrane, Similar examination of SIVMne produced by HUT-78 human T cells did not detect specific incorporation of CyPA into SIV virions, Our results are consistent with the role of CyPA acting early in the infectious process of HIV-1. RP OTT, DE (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,AIDS VACCINE PROGRAM,FREDERICK,MD 21702, USA. NR 24 TC 75 Z9 76 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD SEP PY 1995 VL 11 IS 9 BP 1003 EP 1006 DI 10.1089/aid.1995.11.1003 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA RW230 UT WOS:A1995RW23000001 PM 8554896 ER PT J AU DAGOSTINO, DM CIMINALE, V PAVLAKIS, GN CHIECOBIANCHI, L AF DAGOSTINO, DM CIMINALE, V PAVLAKIS, GN CHIECOBIANCHI, L TI INTRACELLULAR TRAFFICKING OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REV PROTEIN - INVOLVEMENT OF CONTINUED RIBOSOMAL-RNA SYNTHESIS IN NUCLEAR RETENTION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID VIRAL MESSENGER-RNA; GENE-EXPRESSION REQUIRES; TRANS-ACTIVATOR; TARGET SEQUENCE; NUCLEOLAR LOCALIZATION; FUNCTIONAL-ANALYSIS; STRUCTURED REGION; HIV-1; BINDING; TRANSLATION AB We have explored the mechanism directing the intracellular trafficking and nucleolar accumulation of the human immunodeficiency virus type 1 (HIV-1) Rev protein, Treatment of Rev-expressing cells with mycophenolic acid, an inhibitor of inosine monophosphate dehydrogenase, resulted in a redistribution of Rev from the nucleoli to the nucleoplasm and cytoplasm, In contrast, a Rev effector domain mutant was retained in the nucleus, indicating the involvement of this domain in the protein's nuclear retention/nucleocytoplasmic transport, Identical results were obtained by inhibiting transcription using actinomycin D or 5,6-dichlorobenzimidazole riboside, All three drugs were found to inhibit biosynthetic labeling of ribosomal RNA and to disrupt nucleolar morphology, suggesting a correlation between nucleolar/nuclear retention of Rev, continued ribosomal RNA synthesis, and intact nucleolar architecture, Results of binding/immunofluorescence assays using isolated, permeabilized nuclei and extracts of cells expressing Rev demonstrated that the protein is able to bind to nucleoli in vitro, in the absence of active cellular processes or eukaryotic posttranslational modifications, Rev derived from actinomycin D-treated cells showed equivalent binding, indicating that the inhibitor did not directly interfere with the ability of the protein to interact with nucleolar structures, Rev's interaction with nucleoli was directed by the protein's arginine-rich RNA-binding/nucleolar localization domain, and was abrogated by pretreatment of the nuclei with RNaseA, indicating a requirement for RNA, probably ribosomal RNA. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,HUMAN RETROVIRUS SECT,FREDERICK,MD 21702. RP DAGOSTINO, DM (reprint author), UNIV PADUA,INST ONCOL,VIA GATTEMALATA 64,I-35128 PADUA,ITALY. FU NCI NIH HHS [IF32CA60403-01, N01-CO-74101] NR 61 TC 36 Z9 36 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD SEP PY 1995 VL 11 IS 9 BP 1063 EP 1071 DI 10.1089/aid.1995.11.1063 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA RW230 UT WOS:A1995RW23000008 PM 8554903 ER PT J AU COHEN, SG AF COHEN, SG TI CALVIN,JOHN (1509-1564) - FRENCH CHURCHMAN AND RELIGIOUS REFORMER SO ALLERGY PROCEEDINGS LA English DT Item About an Individual RP COHEN, SG (reprint author), NIAID,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1046-9354 J9 ALLERGY PROC JI Allergy Proc. PD SEP-OCT PY 1995 VL 16 IS 5 BP 276 EP 278 PG 3 WC Allergy SC Allergy GA TE184 UT WOS:A1995TE18400011 PM 8566743 ER PT J AU COHEN, SG AF COHEN, SG TI HAMILTON,JOHN (1511-1571) - SCOTTISH ARCHBISHOP SO ALLERGY PROCEEDINGS LA English DT Item About an Individual RP COHEN, SG (reprint author), NIAID,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1046-9354 J9 ALLERGY PROC JI Allergy Proc. PD SEP-OCT PY 1995 VL 16 IS 5 BP 279 EP 281 PG 3 WC Allergy SC Allergy GA TE184 UT WOS:A1995TE18400012 PM 8566744 ER PT J AU COHEN, SG AF COHEN, SG TI VANHELMONT,JEAN,BAPTISTA (1579-1644) - BELGIAN PHYSICIAN AND PIONEER CHEMIST SO ALLERGY PROCEEDINGS LA English DT Item About an Individual RP COHEN, SG (reprint author), NIAID,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1046-9354 J9 ALLERGY PROC JI Allergy Proc. PD SEP-OCT PY 1995 VL 16 IS 5 BP 282 EP 284 PG 3 WC Allergy SC Allergy GA TE184 UT WOS:A1995TE18400013 PM 8566745 ER PT J AU COHEN, SG AF COHEN, SG TI RIOLAN,SEAN (1580-1657) - FRENCH PHYSICIAN AND PIONEER ANATOMIST SO ALLERGY PROCEEDINGS LA English DT Item About an Individual RP COHEN, SG (reprint author), NIAID,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1046-9354 J9 ALLERGY PROC JI Allergy Proc. PD SEP-OCT PY 1995 VL 16 IS 5 BP 285 EP 286 PG 2 WC Allergy SC Allergy GA TE184 UT WOS:A1995TE18400014 PM 8566746 ER PT J AU ARBUSTINI, E MERLINI, G GAVAZZI, A GRASSO, M DIEGOLI, M FASANI, R BELLOTTI, V MARINONE, G MORBINI, P DALBELLO, B CAMPANA, C FERRANS, VJ AF ARBUSTINI, E MERLINI, G GAVAZZI, A GRASSO, M DIEGOLI, M FASANI, R BELLOTTI, V MARINONE, G MORBINI, P DALBELLO, B CAMPANA, C FERRANS, VJ TI CARDIAC IMMUNOCYTE-DERIVED (AL) AMYLOIDOSIS - AN ENDOMYOCARDIAL BIOPSY STUDY IN 11 PATIENTS SO AMERICAN HEART JOURNAL LA English DT Article ID SYSTEMIC AMYLOIDOSIS; NATRIURETIC PEPTIDE; DEPOSITS; FEATURES; HEART; CARDIOMYOPATHY; DIAGNOSIS; DISEASE; ATRIAL AB The objective of this study was to investigate the spectrum of morphologic features in myocardial biopsy specimens from patients with cardiac immunocyte-derived (AL) amyloidosis. Cardiac involvement is the most important predictor of survival in AL amyloidosis. Myocardial biopsy remains the method of choice for diagnosing cardiac amyloidosis when noninvasive studies give equivocal results. Histologic, immunohistochemical, ultrastructural, and morphometric studies were made on myocardial biopsy specimens from 11 patients in whom the diagnosis of AL amyloidosis was based on the demonstration of a monoclonal immunoglobulinopathy and of amyloid deposits in tissues. Histopathologic study showed amyloid in 10 of the 11 biopsies. In one biopsy (Congo red negative), the diagnosis was made by ultrastructural identification of amyloid fibrils. In ail patients, the deposits formed perimyocytic layers that measured up to 18 mu m in thickness. These layers formed along the basement membranes, which were partially preserved in 5 patients and unrecognizable in 6. Interstitial nodular deposits were also present in 5 patients. Immunohistochemical studies for the characterization of the proteins in the amyloid deposits were diagnostic in 1 patient and confirmatory in 10. Nodular deposits, thick perimyocytic layers of amyloid and small myocyte diameters were associated with shorter survival of the patients. Small-vessel involvement and myofilament loss occurred in all patients. In conclusion, myocardial biopsy serves to (1) establish the diagnosis of cardiac amyloidosis; (2) characterize immunohistochemically the proteins in the amyloid fibrils and (3) assess the degree of myocyte damage and atrophy. C1 UNIV PAVIA,POLICLIN SAN MATTEO,IRCCS,DEPT PATHOL,PAVIA,ITALY. UNIV PAVIA,POLICLIN SAN MATTEO,IRCCS,DEPT INTERNAL MED 2,PAVIA,ITALY. UNIV PAVIA,POLICLIN SAN MATTEO,IRCCS,DEPT CARDIOL,PAVIA,ITALY. NHLBI,PATHOL BRANCH,BETHESDA,MD. RI Merlini, Giampaolo/A-3817-2008; Bellotti, Vittorio/A-6201-2014 OI Merlini, Giampaolo/0000-0001-7680-3254; NR 30 TC 34 Z9 35 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD SEP PY 1995 VL 130 IS 3 BP 528 EP 536 DI 10.1016/0002-8703(95)90362-3 PN 1 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RR599 UT WOS:A1995RR59900019 PM 7661071 ER PT J AU CANTILLON, M AF CANTILLON, M TI WHEN THE MIND FAILS - A GUIDE TO DEALING WITH INCOMPETENCY - SILBERFELD,MS, FISH,A SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Book Review RP CANTILLON, M (reprint author), NIMH,GERIATR PSYCHIAT SECT,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD FAL PY 1995 VL 3 IS 4 BP 354 EP 354 PG 1 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA RY064 UT WOS:A1995RY06400012 ER PT J AU PEPPER, AE BUCKLEY, RH SMALL, TN PUCK, JM AF PEPPER, AE BUCKLEY, RH SMALL, TN PUCK, JM TI 2 MUTATIONAL HOTSPOTS IN THE INTERLEUKIN-2 RECEPTOR-GAMMA CHAIN GENE CAUSING HUMAN X-LINKED SEVERE COMBINED IMMUNODEFICIENCY SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID FUNCTIONAL COMPONENT; CELLS; TRANSPLANTATION; DEFICIENCY; CLONING; SCIDX1 AB Human severe combined immunodeficiency (SCID), a syndrome of profoundly impaired cellular and humoral immunity, is most commonly caused by mutations in the X-linked gene for interleukin-2 (IL-2) receptor gamma chain (lL2RG). For mutational analysis of IL2RG in males with SCID, SSCP screening was followed by DNA sequencing. Of 40 IL2RG mutations found in unrelated SCID patients, 6 were point mutations at the CpG dinucleotide at cDNA 690-691, encoding amino acid R226. This residue lies in the extracellular domain of the protein in a region not previously recognized to be significantly conserved in the cytokine receptor gene family, 11 amino acids upstream from the highly conserved WSXWS motif. Three additional instances of mutation at another CpG dinucleotide at cDNA 879 produced a premature termination signal in the introcellular domain of IL2RG, resulting in loss of the SH2-homologous intracellular domain known to be essential for signaling from the IL-2 receptor complex. Mutations at these two hotspots constitute >20% of the X-linked SCID mutations found by our group and a similar proportion of all reported IL2RG mutations. C1 NIH,NATL CTR HUMAN GENOME RES,GENE TRANSFER LAB,BETHESDA,MD 20892. DUKE UNIV,SCH MED,DEPT PEDIAT,DIV ALLERGY & IMMUNOL,DURHAM,NC. DUKE UNIV,SCH MED,DEPT IMMUNOL,DIV ALLERGY & IMMUNOL,DURHAM,NC. MEM HOSP,MEM SLOAN KETTERING CANC CTR,DEPT PEDIAT,DIV IMMUNOL,NEW YORK,NY. FU NIAID NIH HHS [R37 AI18613-13, 9-P01-AI32918] NR 41 TC 38 Z9 39 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP PY 1995 VL 57 IS 3 BP 564 EP 571 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA RR605 UT WOS:A1995RR60500005 PM 7668284 ER PT J AU PAULS, DL OTT, J PAUL, SM ALLEN, CR FANN, CSJ CARULLI, JP FALLS, KM BOUTHILLIER, CA GRAVIUS, TC KEITH, TP EGELAND, JA GINNS, EI AF PAULS, DL OTT, J PAUL, SM ALLEN, CR FANN, CSJ CARULLI, JP FALLS, KM BOUTHILLIER, CA GRAVIUS, TC KEITH, TP EGELAND, JA GINNS, EI TI LINKAGE ANALYSES OF CHROMOSOME-18 MARKERS DO NOT IDENTIFY A MAJOR SUSCEPTIBILITY LOCUS FOR BIPOLAR AFFECTIVE-DISORDER IN THE OLD-ORDER AMISH SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID MANIC-DEPRESSIVE ILLNESS; SEGREGATION ANALYSIS; DNA MARKERS; TRANSMISSION; GENOME; SEARCH; INHERITANCE; RELIABILITY; FAMILY; MAP AB Previously reported linkage of bipolar affective disorder to DNA markers in the pericentromeric region of chromosome 18 was reexamined in a larger homogeneous sample of Old Order Amish families. Four markers (D18S21, D18S53, D18S44, and D18S40) were examined in three kindreds containing 31 bipolar I (BP I) individuals. Although linkage findings were replicated in the one previously studied Amish pedigree containing four BP I individuals, linkage to this region was excluded in the larger sample. If a susceptibility locus for bipolar disorder is located in this region of chromosome 18, it is of minor significance in this population. C1 NEW YORK STATE PSYCHIAT INST & HOSP,NEW YORK,NY. COLUMBIA UNIV,NEW YORK,NY. NIMH,IRP,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. ELI LILLY & CO,LILLY RES LABS,INDIANAPOLIS,IN 46285. UNIV MIAMI,DEPT PSYCHIAT,MIAMI,FL 33152. GENOME THERAPEUT CORP,WALTHAM,MA. RP PAULS, DL (reprint author), YALE UNIV,SCH MED,CTR CHILD STUDY,230 S FRONTAGE RD,NEW HAVEN,CT 06510, USA. FU NIMH NIH HHS [MH28287, MH44292, MH-00508] NR 39 TC 45 Z9 45 U1 2 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP PY 1995 VL 57 IS 3 BP 636 EP 643 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA RR605 UT WOS:A1995RR60500013 PM 7668292 ER PT J AU FERNANDEZSALGUERO, P HOFFMAN, SMG CHOLERTON, S MOHRENWEISER, H RAUNIO, H RAUTIO, A PELKONEN, O HUANG, JD EVANS, WE IDLE, JR GONZALEZ, FJ AF FERNANDEZSALGUERO, P HOFFMAN, SMG CHOLERTON, S MOHRENWEISER, H RAUNIO, H RAUTIO, A PELKONEN, O HUANG, JD EVANS, WE IDLE, JR GONZALEZ, FJ TI A GENETIC-POLYMORPHISM IN COUMARIN 7-HYDROXYLATION - SEQUENCE OF THE HUMAN CYP2A GENES AND IDENTIFICATION OF VARIANT CYP2A6 ALLELES SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID HUMAN-LIVER-MICROSOMES; CYTOCHROME-P450; SUPERFAMILY; METABOLISM; EVOLUTION; SUBFAMILY; MOUSE; RAT AB A group of human cytochrome P450 genes encompassing the CYP2A, CYP2B, and CYP2F subfamilies were cloned and assembled into a 350-kb contig localized on the long arm of chromosome 19. Three complete CYP2A genes-CYP2A6, CYP2A7, and CYP2A13-plus two pseudogenes truncated after exon 5, were identified and sequenced, A variant CYP2A6 allele that differed from the corresponding CYP2A6 and CYP2A7 cDNAs previously sequenced was found and was designated CYP2A6v2. Sequence differences in the CYP2A6v2 gene are restricted to regions encompassing exons 3, 6, and 8, which bear sequence relatedness with the corresponding exons of the CYP2A7 gene, located downstream and centromeric of CYP2A6v2, suggesting recent gene-conversion events, The sequencing of all the CYP2A genes allowed the design of a PCR diagnostic test for the normal CYP2A6 allele, the CYP2A6v2 allele, and a variant-designated CYP2A6v1-that encodes an enzyme with a single inactivating amino acid change. These variant alleles were found in individuals who were deficient in their ability to metabolize the CYP2A6 probe drug coumarin, The allelic frequencies of CYP2A6v1 and CYP2A6v2 differed significantly between Caucasian, Asian, and African-American populations, These studies establish the existence of a new cytochrome P450 genetic polymorphism. C1 NCI, BETHESDA, MD 20892 USA. LAWRENCE LIVERMORE NATL LAB, LIVERMORE, CA USA. UNIV NEWCASTLE UPON TYNE, SCH MED, DEPT PHARMACOL SCI, NEWCASTLE UPON TYNE, TYNE & WEAR, ENGLAND. UNIV OULU, DEPT PHARMACOL & TOXICOL, OULU, FINLAND. NATL CHENG KUNG UNIV, DEPT PHARMACOL, TAINAN 70101, TAIWAN. ST JUDE CHILDRENS RES HOSP, DEPT PHARMACEUT, MEMPHIS, TN 38105 USA. OI Fernandez-Salguero, Pedro M./0000-0003-2839-5027; Idle, Jeff/0000-0002-6143-1520 NR 30 TC 249 Z9 255 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP PY 1995 VL 57 IS 3 BP 651 EP 660 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA RR605 UT WOS:A1995RR60500015 PM 7668294 ER PT J AU SHARARA, FI NIEMAN, LK AF SHARARA, FI NIEMAN, LK TI GROWTH-HORMONE RECEPTOR MESSENGER-RIBONUCLEIC-ACID EXPRESSION IN LEIOMYOMA AND SURROUNDING MYOMETRIUM SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE UTERUS; LEIOMYOMA; MYOMETRIUM; GROWTH HORMONE; POLYMERASE CHAIN REACTION; IN SITU HYBRIDIZATION ID SERUM BINDING-PROTEIN; SMOOTH-MUSCLE TUMORS; INSULIN-LIKE; FACTOR-I; UTERINE LEIOMYOMATA; GENE-EXPRESSION; FIBROIDS; WOMEN AB OBJECTIVE: Uterine leiomyomas are the most common pelvic tumors, occurring in one of four women, and they represent the single most common indication for hysterectomy. The genesis and growth-promoting factors responsible for their development are poorly understood. We speculate that growth hormone may play a role in the initiation of these tumors; women with acromegaly have a higher incidence of leiomyomas and growth hormone promotes uterine growth in rats, with or without the addition of estradiol. We evaluated the presence of growth hormone receptor messenger ribonucleic acid in the human uterus and leiomyomas to investigate whether growth hormone might act directly rather than by hepatic generation of insulin-like growth factor-I. STUDY DESIGN: Paired samples of leiomyomas and adjacent normal myometrium from nine premenopausal women (32 to 52 years old) were collected at surgery. Three patients received a gonadotropin-releasing hormone agonist for 3 months before the surgical procedure; six did not receive any adjuvant therapy. We used a digoxigenin-labeled oligoprobe sharing no homology to the growth hormone-binding protein or to the prolactin receptor, to investigate whether growth hormone receptor messenger ribonucleic acid was present in tissue sections or amplified complementary deoxyribonucleic acid from leiomyoma and the surrounding myometrium. RESULTS: The ratios of growth hormone receptor/reduced glyceraldehyde-phosphate dehydrogenase in leiomyomas and the surrounding myometrium as assessed by densitometry analysis of polymerase chain reaction products were similar and were not altered by gonadotropin-releasing hormone agonist treatment. In situ hybridization localized the growth hormone receptor messenger ribonucleic acid to the nuclei and cytoplasm of leiomyoma and myometrium. CONCLUSION: The presence of growth hormone receptor messenger ribonucleic acid suggests that the human uterus is a target tissue for growth hormone action. Future investigations are needed to investigate further the role of growth hormone in the development of leiomyomas. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 27 TC 17 Z9 17 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 1995 VL 173 IS 3 BP 814 EP 819 DI 10.1016/0002-9378(95)90346-1 PN 1 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA RX497 UT WOS:A1995RX49700025 PM 7573249 ER PT J AU WILCOX, AJ UMBACH, DM HORNSBY, PP HERBST, AL AF WILCOX, AJ UMBACH, DM HORNSBY, PP HERBST, AL TI AGE AT MENARCHE AMONG DIETHYLSTILBESTROL GRANDDAUGHTERS SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE DIETHYLSTILBESTROL; TRANSPLACENTAL EXPOSURE; MENARCHE AB We interviewed 542 women whose mothers were in a randomized trial of diethylstilbestrol. Effects of diethylstilbestrol on the third generation were explored by ascertaining age at menarche for the women's daughters. A total of 123 daughters were greater than or equal to 10 years old (52 exposed and 71 unexposed). Age at menarche was unaffected by mother's prenatal diethylstilbestrol exposure. C1 NIEHS,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709. UNIV VIRGINIA,HLTH SCI CTR,CHARLOTTESVILLE,VA. UNIV CHICAGO,DEPT OBSTET & GYNECOL,CHICAGO,IL 60637. RP WILCOX, AJ (reprint author), NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709, USA. OI Wilcox, Allen/0000-0002-3376-1311 NR 5 TC 7 Z9 8 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 1995 VL 173 IS 3 BP 835 EP 836 DI 10.1016/0002-9378(95)90350-X PN 1 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA RX497 UT WOS:A1995RX49700029 PM 7573253 ER PT J AU EVARTS, RP HU, ZY OMORI, N OMORI, M MARSDEN, ER THORGEIRSSON, SS AF EVARTS, RP HU, ZY OMORI, N OMORI, M MARSDEN, ER THORGEIRSSON, SS TI EFFECT OF VITAMIN-A-DEFICIENCY ON THE INTEGRITY OF HEPATOCYTES AFTER PARTIAL-HEPATECTOMY SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID PROGRAMMED CELL-DEATH; TRANSFORMING GROWTH FACTOR-BETA-1; THYMOCYTE APOPTOSIS; FACTOR-BETA; ACTIVATION; RECEPTOR; JUN; MYC; PROLIFERATION; INVOLVEMENT AB The effect of vitamin A deficient on hepatic regeneration in male and female rats was studied after partial hepatectomy, A fourfold increase in the number of positive dUTP end-labeled nuclei was observed in the deficient animals as early as 30 minutes after partial hepatectomy and their number reached a peak by 8 hours after the operation. The bile duct cells were both morphologically and biochemically intact at all time points. Administration of retinyl palmitate I hour before partial hepatectomy significantly reduced the number of positive nuclei, and treatment with retinyl palmitate 24 or 48 hours before the operation reduced the number of positive cells to the level observed in control vitamin A-supplemented rats, The level of transcripts for c-jun, c-fos, c-myc, and transforming growth factor-pr were increased for an extended period of time in livers of deficient animals, whereas the expression of both p53 and max were unchanged Immunocytochemistry demonstrated the presence of latent transforming growth factor-beta 1 in cells showing evident apoptotic or necrotic changes in their nuclei. This study demonstrates the importance of vitamin A for the survival of hepatocytes both in intact vitamin A-deficient liver and after partial hepatectomy, whereas the ductal cells appear to be less sensitive to vitamin A deficiency. RP EVARTS, RP (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BLDG 37,ROOM 3C28,37 CONVENT DR MSC4255,BETHESDA,MD 20892, USA. NR 38 TC 15 Z9 16 U1 1 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 1995 VL 147 IS 3 BP 699 EP 706 PG 8 WC Pathology SC Pathology GA RU160 UT WOS:A1995RU16000017 PM 7677181 ER PT J AU SUNDAY, ME WILLETT, CG GRAHAM, SA OREFFO, VIC LINNOILA, RI WITSCHI, H AF SUNDAY, ME WILLETT, CG GRAHAM, SA OREFFO, VIC LINNOILA, RI WITSCHI, H TI HISTOCHEMICAL CHARACTERIZATION OF NONNEUROENDOCRINE TUMORS AND NEUROENDOCINE CELL HYPERPLASIA INDUCED IN HAMSTER LUNG BY 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE WITH OR WITHOUT HYPEROXIA SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID NEURO-ENDOCRINE CELLS; MONOCLONAL-ANTIBODIES; FETAL LUNG; K-RAS; DIFFERENTIATION; NEOPLASMS; BOMBESIN; PROLIFERATION; LOCALIZATION; ONCOPROTEIN AB Lung tumors induced by 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone (NNK) with or without hyperoxia have frequent K-ras mutations but only rare p53 mutations, suggesting that this may be a model for non-small cell lung cancers, The goals of the present study were (1) to characterize the histopathology of lung tumors induced in hamsters by NNK with or without O-2 and (2) as a corollary, to quantitate the pulmonary neuroendocrine cell hyperplasia in the different treatment groups early and late in the treatment period. Lung tumors induced by NNK with or without O-2 were 71% adenomas, 22% adenocarcinomas, similar to 4% bronchoalveolar carcinomas, and similar to 4% squamous/adenosquamous carcinomas, One-half of all tumors were positive for the Clara cell antigen CC10 and 21% of NNK-induced tumors were mucin positive, compared with 2% of NNK/O-2-induced tumors (P = 0.003), Immunostaining for PGP9.5 was positive in 5% of tumors induced by NNK alone, but in none of NKK/O-2-induced tumors (P = 0.024), Abundant proliferating cell nuclear antigen occurred in 55% of NNK-induced tumors, compared with 19% of NNK/O-2-induced tumors (P = 0.003), These data indicate that NNK with or without O-2 induces non-neuroendocrine lung tumors, Hyperoxia appears to inhibit cell proliferation and suppress mucinous and partial neuroendocrine differentiation in some of these tumors. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA. UNIV CALIF DAVIS,INST TOXICOL & ENVIRONM HLTH,DAVIS,CA. NCI,BIOMARKERS & PREVENT RES BRANCH,KENSINGTON,MD. RP SUNDAY, ME (reprint author), BRIGHAM & WOMENS HOSP,DEPT PATHOL,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [R01-HL44984] NR 40 TC 28 Z9 28 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 1995 VL 147 IS 3 BP 740 EP 752 PG 13 WC Pathology SC Pathology GA RU160 UT WOS:A1995RU16000021 PM 7677185 ER PT J AU HE, CJ STRIKER, LJ TSOKOS, M YANG, CW PETEN, EP STRIKER, GE AF HE, CJ STRIKER, LJ TSOKOS, M YANG, CW PETEN, EP STRIKER, GE TI RELATIONSHIPS BETWEEN MESANGIAL CELL-PROLIFERATION AND TYPE-I AND TYPE-IV COLLAGEN MESSENGER-RNA LEVELS IN-VITRO SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE CELL ATTACHMENT; EXTRACELLULAR MATRIX ID SMOOTH-MUSCLE CELLS; EXTRACELLULAR-MATRIX; GENE-EXPRESSION; GROWTH-HORMONE; GLOMERULOSCLEROSIS; ADHESION; FIBRONECTIN; CULTURE; ORGANIZATION; FIBROBLASTS AB Changes in the composition of the mesangial extracellular matrix (ECM) and cell turnover are present in glomerular disease. To determine if ECM changes play a role in perpetuating mesangial cell dysfunction, we examined a line of mouse mesangial cells cultured on films or gels of several ECM components and also on methyl cellulose, an inert substrate that prevents attachment. Cells on films of fibronectin or type IV or I collagen had persistently high growth rates and high levels of alpha(1)-I and alpha(1)-IV collagen mRNAs. In contrast, on gels of type IV or I collagen or matrigel, the growth rate was low. The alpha(1)-IV collagen mRNA levels were low on type TV collagen gel or matrigel, whereas the alpha(1)-I collagen mRNA levels remained high. In contrast, the alpha(1)-I collagen mRNA levels were low on type I collagen gel, and the alpha(1)-IV collagen mRNA levels were high. Cells on methyl cellulose formed floating aggregates, did not proliferate, and had a 5- to 10-fold decrease in both alpha(1)-I and alpha(1)-IV collagen mRNA levels. These phenotypic changes were largely reversible. Finally, when matrigel was layered over cells on fibronectin films, alpha(1)-IV collagen mRNA levels decreased, but alpha(1)-I collagen mRNA levels and proliferation remained high. Thus proliferation and alpha(1)-I and alpha(1)-IV collagen mRNA levels in mesangial cells were independently regulated and depended on attachment and the nature of the adjacent matrix. C1 NIDDK, METAB DIS BRANCH, RENAL CELL BIOL SECT, BETHESDA, MD 20892 USA. NCI, PATHOL LAB, BETHESDA, MD 20892 USA. NR 34 TC 23 Z9 23 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD SEP PY 1995 VL 269 IS 3 BP C554 EP C562 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA RV403 UT WOS:A1995RV40300003 PM 7573384 ER PT J AU MARPLES, D KNEPPER, MA CHRISTENSEN, EI NIELSEN, S AF MARPLES, D KNEPPER, MA CHRISTENSEN, EI NIELSEN, S TI REDISTRIBUTION OF AQUAPORIN-2 WATER CHANNELS INDUCED BY VASOPRESSIN IN RAT-KIDNEY INNER MEDULLARY COLLECTING DUCT SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE REGULATED EXOCYTOSIS; MEMBRANE TRAFFICKING ID URINARY-BLADDER; TUBULE; ENDOCYTOSIS; CELLS; TRANSPORT; RECEPTOR; GP330; FLOW AB Aquaporin-2 (AQPB) is the predominant vasopressin-regulated water channel of the renal collecting duct. We tested whether vasopressin induces translocation of AQP2 from intracellular vesicles into the apical plasma membrane. AQP2 was quantitated in plasma membrane and intracellular vesicle fractions prepared from the inner medulla of one kidney from each rat before or 20 min after intravenous 1-desamino-8-D-arginine vasopressin (DDAVP) treatment, using immunoblotting and densitometry. Contralateral kidneys were prepared for immunofluorescence and immunoelectron microscopy. Immunoblotting revealed that, compared with untreated controls, DDAVP treatment significantly increased the fraction of AQP2 protein associated with the plasma membrane fraction relative to intracellular vesicles. This increase averaged 2.0-fold in untreated rats and 2.9-fold in rats water loaded for 12 h. Water loading, presumably by suppressing circulating vasopressin levels, decreased the fraction of AQPB associated with the plasma membrane by 55%, suggesting retrieval of AQP2 from the plasma membrane. In rats sequentially thirsted for 48 h to increase expression and then water loaded for 72 h to minimize plasma membrane labeling, DDAVP caused a 12-fold increase in the plasma membrane to intracellular vesicle labeling ratio. The accentuation of the DDAVP response seen after water loading is consistent with the observed increase in the fraction of AQP2 in the intracellular pool available for insertion. Immunofluorescence confirmed a marked DDAVP-induced redistribution of AQPB from intracellular to plasma membrane domains. Furthermore, quantitative immunoelectron microscopy demonstrated a 3.4-fold increase in apical plasma membrane to intracellular vesicle labeling ratio. These results provide a direct in vivo demonstration of vasopressin-induced translocation of AQP2 into the apical plasma membrane. C1 UNIV AARHUS, INST ANAT, DEPT CELL BIOL, DK-8000 AARHUS C, DENMARK. NHLBI, KIDNEY & ELECTROLYTE METAB LAB, BETHESDA, MD 20892 USA. NR 39 TC 233 Z9 234 U1 4 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD SEP PY 1995 VL 269 IS 3 BP C655 EP C664 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA RV403 UT WOS:A1995RV40300014 PM 7573395 ER PT J AU HABER, RS WILSON, CM WEINSTEIN, SP PRITSKER, A CUSHMAN, SW AF HABER, RS WILSON, CM WEINSTEIN, SP PRITSKER, A CUSHMAN, SW TI THYROID-HORMONE INCREASES THE PARTITIONING OF GLUCOSE TRANSPORTERS TO THE PLASMA-MEMBRANE IN ARL-15 CELLS SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE 8-DEOXYGLUCOSE; 3,5,3'-TRIIODO-L-THYRONINE; GLUCOSE TRANSPORT ID RAT ADIPOSE-CELLS; SUBCELLULAR TRAFFICKING; 3T3-L1 CELLS; INSULIN; GLUT4; STIMULATION; HYPERTHYROIDISM; MUSCLE; MECHANISMS; BISMANNOSE AB The stimulation of glucose transport by 3,5,3'-triiodo-L-thyronine (T-3) in the liver-derived ARL 15 cell line is only partly attributable to increased GLUT-1 glucose transporter gene expression. To test the hypothesis that T-3 increases the partitioning of GLUT-1 to the cell surface, we quantitated surface GLUT-1 using the photolabel ATB-[H-3]BMPA. In control cells only similar to 20% of total cellular GLUT-1 was present at the cell surface. T-3 treatment (100 nM) for 6 h increased the rate of 2-deoxy[H-3]glucose (2-DG) uptake by 30, 92, and 95% in three experiments and increased surface GLUT-1 photolabeling by 17, 81, and 72%, respectively, with no increase in total cellular GLUT-1. T-3 treatment for 48 h increased 2-DG uptake by 143, 172, and 216% in three experiments and increased cell surface GLUT-1 photolabeling by 88, 161, and 184%, respectively, with smaller increases in total cellular GLUT-1. T-3 treatment for 48 h thus increased the fraction of cellular GLUT-1 at the plasma membrane from 21 +/- 2 to 35 +/- 3% (SE). We conclude that most of the early (6-h) stimulation of glucose transport by T-3 in ARL 15 cells is mediated by an increase in the partitioning of GLUT-1 to the plasma membrane. With more chronic T-3 treatment (48 h), the enhanced surface partitioning of GLUT-1 is persistent and is superimposed on an increase in total cellular GLUT-1, accounting for a further increase in glucose transport. C1 NIDDKD, DIABET BRANCH, EXPTL DIABET METAB & NUTR SECT, BETHESDA, MD 20892 USA. RP HABER, RS (reprint author), MT SINAI SCH MED, DEPT MED, BOX 1055, 1 GUSTAVE L LEVY PL, NEW YORK, NY 10029 USA. FU NIDDK NIH HHS [DK-41674, DK-02057] NR 28 TC 5 Z9 5 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD SEP PY 1995 VL 269 IS 3 BP E605 EP E610 PG 6 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA RV599 UT WOS:A1995RV59900025 PM 7573440 ER PT J AU YOUNES, A BOLUYT, MO ONEILL, L MEREDITH, AL CROW, MT LAKATTA, EG AF YOUNES, A BOLUYT, MO ONEILL, L MEREDITH, AL CROW, MT LAKATTA, EG TI AGE-ASSOCIATED INCREASE IN RAT VENTRICULAR ANP GENE-EXPRESSION CORRELATES WITH CARDIAC-HYPERTROPHY SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE AGING; SENESCENCE ID ATRIAL NATRIURETIC FACTOR; SEQUENCE-ANALYSIS; MESSENGER-RNA; HEART-FAILURE; PEPTIDE; TISSUE; PURIFICATION; ATRIOPEPTIN; POLYPEPTIDE; SENESCENCE AB Atrial natriuretic peptide (ANP), a cardiac-specific hormone, is stored in the atria and released in response to atrial stretch. During cardiac hypertrophy, ANP gene expression is markedly upregulated in the left ventricle (LV). Because the hearts of normotensive senescent rats exhibit left atrial (LA) and left ventricular (LV) hypertrophy and dilatation, we examined ANP mRNA levels by Northern blot analysis and ANP peptide concentrations by radioimmunoassay in atria, LVs, and plasma of rats at 2, 6, 18, and 22-24 mo of age. Compared with LVs of B-mo-old rats, the LV-to-body weight ratio was elevated 30% by 18 mo of age, whereas levels of ANP mRNA were elevated twofold (not significant) and sevenfold (P < 0.05) in the LV of 18- and 22- to 24-mo-old rats, respectively. The concentration of immunoreactive ANP (ir-ANP) exhibited a four- to fivefold increase in LVs of 18- and 22- to 24-mo-old rats compared with values for 6-mo-old rats (43 +/- 4 pmol/g wet wt; means +/- SE). Among 18- and 22- to 24-mo-old rats a significant correlation was observed between ANP peptide concentration and LV hypertrophy (r(2) = 0.64). Levels of ANP mRNA and ir-ANP in the atria exhibited only modest changes with aging. Plasma ir-ANP concentrations were 2.4-fold higher at 18 mo of age compared with the 6-mo value of 9.7 +/- 1.9 fmol/ml but were intermediate at 22 mo of age (16.8 +/- 1.5 fmol/ml). Given the size of the LV relative to the atria, these data suggest LV endocrine release may contribute significantly to circulating ANP levels in the senescent rat. The correlation between ir-ANP and hypertrophy in the LVs of older rats suggests that a common mechanism(s) is responsible for the age-associated increases in ANP gene expression and cardiac hypertrophy. C1 NIA, GERONTOL RES CTR, CARDIOVASC SCI LAB, BALTIMORE, MD 21224 USA. UNIV AUVERGNE CLERMONT FERRAND, F-63172 CLERMONT FERRAND, FRANCE. NR 35 TC 33 Z9 35 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD SEP PY 1995 VL 269 IS 3 BP H1003 EP H1008 PG 6 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA RV400 UT WOS:A1995RV40000033 ER PT J AU JI, CM CARDOSO, WV GEBREMICHAEL, A PHILPOT, RM BUCKPITT, AR PLOPPER, CG PINKERTON, KE AF JI, CM CARDOSO, WV GEBREMICHAEL, A PHILPOT, RM BUCKPITT, AR PLOPPER, CG PINKERTON, KE TI PULMONARY CYTOCHROME-P-450 MONOOXYGENASE SYSTEM AND CLARA CELL-DIFFERENTIATION IN RATS SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE LUNG DEVELOPMENT; IMMUNOHISTOCHEMISTRY; ULTRASTRUCTURAL MORPHOMETRY ID RABBIT LUNG; HUMAN-TISSUES; EXPRESSION; LOCALIZATION; INDUCTION; REDUCTASE AB Because a number of studies suggest that the developmental expression of cytochrome P-450s (CYP) in Clara cells is species specific, this study was designed to compare the developmental patterns of the isoform CYP2B and NADPH reductase protein expression and CYP2B activity with the time course of smooth endoplasmic reticulum (SER) formation in Clara cells of rat lung. Pulmonary CYP2B activity measured as pentoxyresorufin O-dealkylation in lung homogenates was not detectable before 7 days postnatal age, but was detectable at adult levels at 50 days postnatal age. In Clara cells, CYP2B and NADPH reductase were detected immunohistochemically at 4 days postnatal age and at adult levels at 10 days postnatal age. The volume density of SER in Clara cells of terminal bronchioles measured morphometrically increased significantly with postnatal age. We conclude that in the rat 1) CYP2B and NADPH reductase distribution and CYP2B activity are age dependent; 2) the increase in Clara cell SER precedes the expression of CYP2B protein; 3) cellular appearance of CYP2B protein precedes CYP activity; and 4) SER appearance and P-450 protein expression do not occur uniformly in differentiating Clara cells, even within the same bronchiole. C1 UNIV CALIF DAVIS, SCH VET MED, DEPT ANAT PHYSIOL & CELL BIOL, DAVIS, CA 95616 USA. UNIV CALIF DAVIS, SCH VET MED, DEPT MOLEC BIOSCI, DAVIS, CA 95616 USA. BOSTON UNIV, SCH MED, CTR PULM, BOSTON, MA 02118 USA. NIEHS, CELLULAR & MOLEC PHARMACOL LAB, RES TRIANGLE PK, NC 27709 USA. FU NCRR NIH HHS [RR-00169]; NHLBI NIH HHS [HL-43032]; NIEHS NIH HHS [ES-05707] NR 30 TC 17 Z9 17 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD SEP PY 1995 VL 269 IS 3 BP L394 EP L402 PG 9 WC Physiology; Respiratory System SC Physiology; Respiratory System GA RV607 UT WOS:A1995RV60700016 PM 7573474 ER PT J AU SUGAHARA, K RUBIN, JS MASON, RJ ARONSEN, EL SHANNON, JM AF SUGAHARA, K RUBIN, JS MASON, RJ ARONSEN, EL SHANNON, JM TI KERATINOCYTE GROWTH-FACTOR INCREASES MESSENGER-RNAS FOR SP-A AND SP-B IN ADULT-RAT ALVEOLAR TYPE-II CELLS IN CULTURE SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE LUNG; SURFACTANT PROTEINS ID PULMONARY SURFACTANT PROTEIN; AMINO-ACID SEQUENCE; EPITHELIAL-CELLS; DNA-SYNTHESIS; FETAL LUNG; SP-C; EXPRESSION; CDNA; DIFFERENTIATION; NUCLEOTIDE AB The production of pulmonary surfactant, a complex of phospholipids and lung-specific surfactant proteins, is a primary function of alveolar type II cells. Although previous studies have demonstrated a role for cell-extracellular matrix interactions and normal cell shape in the maintenance of differentiated function in primary cultures of adult rat type II cells, a positive role for growth factors in surfactant protein gene expression in isolated normal adult type II cells has not been reported. In the present study, we have examined the effects of a panel of hormones, growth factors, and cytokines on the expression of mRNAs for surfactant proteins A, B, and C (SP-A, SP-B, and SP-C). Our results show that keratinocyte growth factor (KGF) induced a two- to threefold increase in steady-state levels of mRNAs for SP-A and SP-B, but had no effect on or decreased SP-C mRNA. The increase in SP-A mRNA was accompanied by an increase in SP-A protein. The effects of KGF were both dose and time dependent, and they could be neutralized by a monoclonal antibody against KGF. The effects of KGF were mimicked by acidic fibroblast growth factor, which will bind the KGF receptor. We conclude that KGF can support differentiation of alveolar type II cells as well as act as a mitogen, thus suggesting an important role for KGF in maintenance of the alveolar epithelium. C1 NATL JEWISH CTR IMMUNOL & RESP MED, DEPT MED, DENVER, CO 80206 USA. NCI, CELLULAR & MOLEC BIOL LAB, BETHESDA, MD 20892 USA. FU NHLBI NIH HHS [HL-29891, HL-27353] NR 48 TC 78 Z9 79 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD SEP PY 1995 VL 269 IS 3 BP L344 EP L350 PG 7 WC Physiology; Respiratory System SC Physiology; Respiratory System GA RV607 UT WOS:A1995RV60700010 PM 7573468 ER PT J AU CORWIN, RL ROWE, PM CRAWLEY, JN AF CORWIN, RL ROWE, PM CRAWLEY, JN TI GALANIN AND THE GALANIN ANTAGONIST M40 DO NOT CHANGE FAT INTAKE IN A FAT-CHOW CHOICE PARADIGM IN RATS SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE FEEDING; NEUROPEPTIDES; PARAVENTRICULAR NUCLEUS OF THE HYPOTHALAMUS; DIET; OBESITY ID STIMULATION; HYPOTHALAMUS; PREFERENCES; SECRETION; PATTERNS; PEPTIDE; OBESITY AB The neuropeptide galanin has been proposed to play a role in the regulation of fat intake. The purpose of the present investigation was to determine if galanin and the galanin receptor antagonist M40 would have selective effects on fat intake in a fat-chow choice paradigm in rats. Rats were adapted to 22-h access to chow alone and 2-h daily access to separate sources of fat and chow in the early dark cycle. Galanin (300 pmol, 1 nmol) or M40 (2-500 pmol) was microinjected bilaterally into the paraventricular nucleus of the hypothalamus (PVN) before the 2-h choice period, and chow and fat intake were measured. M40 had no effect on chow or fat intake. Galanin stimulated chow intake and increased the ratio of chow to fat consumed but had no significant effect on fat intake alone. These results suggest that endogenous galanin in the PVN may not play a primary role in the regulation of fat intake when fat is available in addition to a nutritionally balanced diet. RP CORWIN, RL (reprint author), NIMH, EXPTL THERAPEUT BRANCH, BEHAV NEUROPHARMACOL SECT, BLDG 10, RM 4N212, BETHESDA, MD 20892 USA. NR 31 TC 32 Z9 33 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regulat. Integr. Compar. Physiol. PD SEP PY 1995 VL 269 IS 3 BP R511 EP R518 PG 8 WC Physiology SC Physiology GA RW600 UT WOS:A1995RW60000005 PM 7573550 ER PT J AU LIANG, CT BARNES, J AF LIANG, CT BARNES, J TI RENAL EXPRESSION OF OSTEOPONTIN AND ALKALINE-PHOSPHATASE CORRELATES WITH BUN LEVELS IN AGED RATS SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY LA English DT Article DE RENAL DYSFUNCTION; GENE EXPRESSION; HYPERPARATHYROIDISM; RENAL CALCIFICATION; AGING; BLOOD UREA NITROGEN ID PARATHYROID-HORMONE; DEVELOPMENTAL EXPRESSION; GENE-EXPRESSION; GROWTH-FACTORS; MESSENGER-RNA; PROTEIN; KIDNEY; CELLS; BONE; CALCIUM AB Renal expression of alkaline phosphatase (AP) and osteopontin (OP) in rats of different age was examined. Northern blot hybridization showed that AP mRNA was reduced moderately, whereas OP mRNA was stimulated drastically in old rats. Dot-blot quantitation analysis showed that AP mRNA decreased 30% in 24-compared with 6-mo-old rats. In contrast, OP mRNA increased 3.1- and 9.1-fold, respectively, in 12- and 24-mo-old rats. beta-Actin mRNA did not change with age. Blood urea nitrogen (BUN) increased 47 and 187% in 12- and 24-mo-old rats, respectively. Correlation analysis showed that BUN correlated negatively with AP mRNA and positively with OP mRNA. No correlation was observed with beta-actin. The expression of these markers was also examined in femurs. AP and OP mRNAs were marginally reduced in old bones. To test whether the correlation also exists in other types of renal insufficiency, we examined these parameters in young rats infused with parathyroid hormone (PTH). BUN was elevated 3.5-fold, whereas AP mRNA decreased 48%, and OP mRNA increased 15.3-fold in kidneys of PTH-treated rats. To elucidate the possible mechanisms that lead to the overexpression of OP in kidney, we examined the expression of transforming growth factor-beta 1 (TGF-beta 1) mRNA. No significant differences in TGF-beta 1 expression were observed between young and old rats and control and PTH-treated young rats. Changes in the expression of OP were also visualized by immunostaining of renal sections. Alterations in the levels of OP and AP were validated by Western blot analysis and enzyme assay of homogenate, respectively. Histological examination showed lesions of nephrons in old rats and PTH-infused young rats, whereas gross calcification was observed only in kidneys of PTH-treated young rats. These findings suggest that some renal proteins, notably OP and AP, can be used as cellular markers for renal dysfunction associated with senescence or other renal diseases. RP LIANG, CT (reprint author), NIA, GERONTOL RES CTR, 4940 EASTERN AVE, BALTIMORE, MD 21224 USA. NR 32 TC 13 Z9 13 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6127 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Fluid Electrol. Physiol. PD SEP PY 1995 VL 269 IS 3 BP F398 EP F404 PG 7 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA RV402 UT WOS:A1995RV40200013 PM 7573489 ER PT J AU BERENGUER, J ALLENDE, MC LEE, JW GARRET, K LYMAN, C ALI, NM BACHER, J PIZZO, PA WALSH, TJ AF BERENGUER, J ALLENDE, MC LEE, JW GARRET, K LYMAN, C ALI, NM BACHER, J PIZZO, PA WALSH, TJ TI PATHOGENESIS OF PULMONARY ASPERGILLOSIS - GRANULOCYTOPENIA VERSUS CYCLOSPORINE AND METHYLPREDNISOLONE-INDUCED IMMUNOSUPPRESSION SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID BONE-MARROW TRANSPLANT; FUNGAL-INFECTIONS; AMPHOTERICIN-B; INVASIVE ASPERGILLOSIS; INVIVO; INVITRO; RABBITS; RECIPIENTS; FUMIGATUS; DISEASE AB Patients with chemotherapy-induced granulocytopenia for neoplastic diseases and those receiving cyclosporin A plus corticosteroids for prevention and treatment of organ transplant rejection are two immunologically distinct patient populations with high risks for development of invasive pulmonary aspergillosis. In order to compare the pathogenesis of aspergillosis in these two high-risk populations and to further characterize the role of cyclosporin A in development of pulmonary aspergillosis, we studied the patterns of infection and inflammation in two clinically applicable rabbit models of invasive pulmonary aspergillosis. There were striking differences in the patterns of infection and inflammation of invasive pulmonary aspergillosis according to the type of underlying immune defect. Among rabbits challenged with the same intratracheal inoculum, there was a 100% mortality for invasive pulmonary aspergillosis in profoundly granulocytopenic rabbits in comparison with a 100% survival in rabbits immunosuppressed with cyclosporin A plus methylprednisolone (CsA+MP). Lesions of pulmonary aspergillosis in granulocytopenic rabbits consisted predominantly of coagulative necrosis, intraalveolar hemorrhage, and scant mononuclear inflammatory infiltrate. By comparison, pulmonary foci in rabbits immunosuppressed by CsA+MP consisted mainly of neutrophilic and monocytic infiltrates, inflammatory necrosis, and scant intraalveolar hemorrhage. There was extensive infiltration by hyphae with angioinvasion in granulocytopenic rabbits, whereas conidia in various stages of germination predominated in CsA+MP-treated animals in which there was a paucity of hyphae or angioinvasion. Extrapulmonary disease predominated in granulocytopenic rabbits. Methylprednisolone was the major immunosuppressive drug in rabbits treated with CsA+MP. Cyclosporin A alone did not increase the progression of pulmonary aspergillosis and did so only when used chronically with methylprednisolone. C1 NCI,INFECT DIS SECT,PEDIAT BRANCH,BETHESDA,MD 20892. NIH,VET RESOURCES PROGRAM,BETHESDA,MD 20892. OI Berenguer, Juan/0000-0001-8541-8200 NR 35 TC 126 Z9 132 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD SEP PY 1995 VL 152 IS 3 BP 1079 EP 1086 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA RT887 UT WOS:A1995RT88700036 PM 7663787 ER PT J AU OLLO, C ALIM, TN ROSSE, RB CUNNINGHAM, S GILLIS, T KHAN, M GREEN, T RICCI, J DEUTSCH, SI AF OLLO, C ALIM, TN ROSSE, RB CUNNINGHAM, S GILLIS, T KHAN, M GREEN, T RICCI, J DEUTSCH, SI TI EVALUATING CRAVING IN CRACK-COCAINE ABUSERS SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID URGES; BROMOCRIPTINE; DESIPRAMINE; ABSTINENCE AB The authors evaluated the psychometric properties of a 33-item Likert-scale questionnaire assessing subcomponents of craving in 77 crack-cocaine abusers. Split-half and test-retest correlations were moderate to strong, indicating good internal reliability. High correlations with traditional visual analog scale measures of drug thoughts and cravings (but not other symptoms) support the questionnaire's validity as a measure of subjective craving. An exploratory factor analysis indicated that craving in these treatment-seeking crack-cocaine abusers is motivated both by the positive reinforcing properties of cocaine and by seeking relief from negative symptoms. A previous study using a similar questionnaire found that craving in non-treatment-seeking drug users was motivated primarily by the desire and intention to use cocaine. The results support the notion that subcomponents of craving exist and may vary with motivational state (i.e., those in treatment vs. non-treatment-seekers). C1 DEPT VET AFFAIRS MED CTR,PSYCHIAT SERV 116A,WASHINGTON,DC 20422. DEPT VET AFFAIRS MED CTR,VET AFFAIRS NIDA RES UNIT,WASHINGTON,DC 20422. NR 17 TC 6 Z9 7 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD FAL PY 1995 VL 4 IS 4 BP 323 EP 330 PG 8 WC Substance Abuse SC Substance Abuse GA TC658 UT WOS:A1995TC65800006 ER PT J AU KINDY, MS DEBEER, FC MARKESBERY, WR PRAS, M AKSENTIJEVICH, I KASTNER, D KYLE, R SOLOMON, A WOO, P AF KINDY, MS DEBEER, FC MARKESBERY, WR PRAS, M AKSENTIJEVICH, I KASTNER, D KYLE, R SOLOMON, A WOO, P TI APOLIPOPROTEIN-E GENOTYPES IN AA AND AL AMYLOIDOSES SO AMYLOID-INTERNATIONAL JOURNAL OF EXPERIMENTAL AND CLINICAL INVESTIGATION LA English DT Article DE APOLIPOPROTEIN E; AMYLOID; POLYMERASE CHAIN REACTION; GENOTYPE ID FAMILIAL MEDITERRANEAN FEVER; ONSET ALZHEIMER-DISEASE; E POLYMORPHISM; BETA-PEPTIDE; ALLELE; FREQUENCY; ASSOCIATION; EPSILON-4; BINDING; PROTEIN AB Apolipoprotein E (apoE) is associated with senile plaques in Alzheimer's disease (AD), and present in amyloid deposits in a variety of systemic amyloidoses. Recently, studies have shown that apoE4 allelic frequency is increased in patients with sporadic and familial late-onset AD and that apoE4 may represent a susceptibility gene for late-onset AD. We addressed the issue of whether a similar association of apoE4 exists in a number of systemic amyloidoses. Tissue was obtained from control subjects, AD patients, familial Mediterranean fever (FMF) patients, amyloid A (AA) amyloid secondary to juvenile chronic arthritis (JCA), and amyloid of the light chain type (myeloma or AL). There was a strong correlation of the apoE4 allele with sporadic and late-onset AD, but no significant increase in apoE4 with other amyloidoses. These data suggest that whereas apoE4 may be a risk factor in AD, it is not in other amyloidoses. However given the association of apoE with all these amyloidoses, the possibility cannot be excluded that this apolipoprotein could be involved in systemic amyloidoses on an isotype non-selective basis. C1 UNIV KENTUCKY,DEPT SURG,LEXINGTON,KY 40536. UNIV KENTUCKY,DEPT MED,LEXINGTON,KY 40536. UNIV KENTUCKY,VET ADM MED CTR,LEXINGTON,KY 40536. UNIV KENTUCKY,SANDERS BROWN CTR AGING,LEXINGTON,KY 40536. UNIV KENTUCKY,DEPT PATHOL,LEXINGTON,KY 40536. TEL AVIV UNIV,CHAIM SHEBA MED CTR,HELLER INST MED RES,TEL HASHOMER,ISRAEL. NIAMSD,BETHESDA,MD 20892. MAYO CLIN,ROCHESTER,MN. UNIV TENNESSEE,MED CTR,DEPT MED,KNOXVILLE,TN. MRC,CLIN RES CTR,HARROW HA1 3UJ,MIDDX,ENGLAND. RP KINDY, MS (reprint author), UNIV KENTUCKY,DEPT BIOCHEM,800 ROSE ST,LEXINGTON,KY 40536, USA. NR 25 TC 14 Z9 14 U1 1 U2 1 PU PARTHENON PUBLISHING GROUP PI CARNFORTH LANCASHIRE PA CASTERTON HALL, CARNFORTH LANCASHIRE, ENGLAND LA6 2LA SN 1350-6129 J9 AMYLOID JI Amyloid-Int. J. Exp. Clin. Investig. PD SEP PY 1995 VL 2 IS 3 BP 159 EP 162 DI 10.3109/13506129509036919 PG 4 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA RX208 UT WOS:A1995RX20800003 ER PT J AU MA, Y ITO, Y AF MA, Y ITO, Y TI CHIRAL SEPARATION BY HIGH-SPEED COUNTERCURRENT CHROMATOGRAPHY SO ANALYTICAL CHEMISTRY LA English DT Article AB Various parameters involved in the chiral separation of (+/-)-DNB-amino acids were investigated using N-dodecanoyl-L-proline-3,5-dimethylanilide as a chiral selector (CS) and two-phase solvent systems composed of hexane/ethyl acetate/methanol/10 mM hydrochloric acid at various volume ratios. The results indicated that increasing the concentration or net amount of the CS in the stationary phase improves both separation factor (alpha) and peak resolution (R(s)). The hydrophobicity of the solvent system also increases the alpha value of the racemate while it affects the peak resolution differently according to the partition coefficient of the racemate. Overall results indicated that the best separation of a racemate will be achieved by applying a high CS concentration in the-organic phase while adjusting the hydrophobicity of the solvent system so that the partition coefficient of the racemate falls between 0.6 and 0.8. The peak resolution will be further increased by using a longer and/or greater internal diameter coiled column. C1 NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. NR 9 TC 40 Z9 45 U1 5 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD SEP 1 PY 1995 VL 67 IS 17 BP 3069 EP 3074 DI 10.1021/ac00113a049 PG 6 WC Chemistry, Analytical SC Chemistry GA RR260 UT WOS:A1995RR26000054 PM 8779424 ER PT J AU FEIERMAN, DE MELNIKOV, Z POHL, LR AF FEIERMAN, DE MELNIKOV, Z POHL, LR TI PRODUCTION OF TRIFLUOROACETYLED-ADDUCTS FROM HALOTHANE BY TRANSDUCED HEP-G2 CELLS SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 CUNY MT SINAI SCH MED,DEPT ANESTHESIOL,NEW YORK,NY 10029. NHLBI,MOLEC TOXICOL SECT,BETHESDA,MD 20892. NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1995 VL 83 IS 3A SU S BP A345 EP A345 PG 1 WC Anesthesiology SC Anesthesiology GA RX685 UT WOS:A1995RX68500345 ER PT J AU LINDEMAN, KS BAKER, SG AF LINDEMAN, KS BAKER, SG TI FACTORS INFLUENCING UTERINE RELAXATION BY HALOTHANE IN NONGRAVID AND GRAVID RATS SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 JOHNS HOPKINS MED INST,BALTIMORE,MD 21287. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1995 VL 83 IS 3A SU S BP A994 EP A994 PG 1 WC Anesthesiology SC Anesthesiology GA RX685 UT WOS:A1995RX68500994 ER PT J AU LIU, M MAX, MB ROBINOVITZ, E BENNETT, GJ AF LIU, M MAX, MB ROBINOVITZ, E BENNETT, GJ TI CAPSAICIN-EVOKED ALLODYNIA - A COMPARISON OF 3 METHODS SO ANESTHESIOLOGY LA English DT Meeting Abstract ID MECHANICAL HYPERALGESIA C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. HOSP UNIV PENN,DEPT ANESTHESIA,PHILADELPHIA,PA. NR 3 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1995 VL 83 IS 3A SU S BP A863 EP A863 PG 1 WC Anesthesiology SC Anesthesiology GA RX685 UT WOS:A1995RX68500863 ER PT J AU TAKAHASHI, H KIRSCH, JR HASHIMOTO, K LONDON, ED TRAYSTMAN, RJ AF TAKAHASHI, H KIRSCH, JR HASHIMOTO, K LONDON, ED TRAYSTMAN, RJ TI PPBP[4-PHENYL-1-(4-PHEYNLBUTYL)PIPERIDINE], A POTENT SIGMA-RECEPTOR LIGAND, DECREASES BRAIN INJURY FOLLOWING TRANSIENT FOCAL ISCHEMIA IN RATS SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 JOHNS HOPKINS MED INST,DEPT ANESTHESIOL CCM,BALTIMORE,MD 21287. NATL INST DRUG ABUSE,BALTIMORE,MD 21287. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1995 VL 83 IS 3A SU S BP A594 EP A594 PG 1 WC Anesthesiology SC Anesthesiology GA RX685 UT WOS:A1995RX68500594 ER PT J AU SHAKIL, AO CONRYCANTILENA, C ALTER, HJ HAYASHI, P KLEINER, DE TEDESCHI, V KRAWCZYNSKI, K CONJEEVARAM, HS SALLIE, R DIBISCEGLIE, AM MELPOLDER, JC HOOFNAGLE, JH AF SHAKIL, AO CONRYCANTILENA, C ALTER, HJ HAYASHI, P KLEINER, DE TEDESCHI, V KRAWCZYNSKI, K CONJEEVARAM, HS SALLIE, R DIBISCEGLIE, AM MELPOLDER, JC HOOFNAGLE, JH TI VOLUNTEER BLOOD-DONORS WITH ANTIBODY TO HEPATITIS-C VIRUS - CLINICAL, BIOCHEMICAL, VIROLOGICAL, AND HISTOLOGIC FEATURES SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE HEPATITIS C; HEPATITIS C VIRUSES; HEPATITIS ANTIBODIES; BLOOD DONORS; ALANINE AMINOTRANSFERASE ID NON-B-HEPATITIS; NON-A-HEPATITIS; LIVER-DISEASE; POSTTRANSFUSION HEPATITIS; UNITED-STATES; INFECTION; SERUM; HCV; RNA; HISTORY AB Objective: To assess the clinical significance of antibody to hepatitis C virus (anti-HCV) in volunteer blood donors. Design: Prospective cohort study. Setting: National Institutes of Health Clinical Center, a tertiary referral research hospital. Patients: 60 anti-HCV-positive blood donors, divided into three groups of 20 persons each: Group I had normal alanine aminotransferase levels, group II had levels elevated to values less than twice the normal range, and group HI had levels elevated to values greater than twice the normal range. Measurements: Medical history, results of laboratory and virologic testing, and percutaneous liver biopsy findings. Results: Participants with normal alanine aminotransferase levels were older and more often female than those with abnormal levels. The source of infection, duration of disease, symptom score, and amount of alcohol consumed were similar in the three groups. Hepatitis C virus RNA was detectable in 85% of participants, more commonly in the groups with elevated alanine aminotransferase levels (95%) than in the group with normal levels (65%); however, titers were similar in all groups. Examination of liver biopsy specimens showed chronic hepatitis in 54 participants (90%) and cirrhosis in 1 participant. The only normal liver biopsy specimens (n = 3) were those from participants who were HCV RNA negative and had normal alanine aminotransferase levels. Conclusions: Most blood donors with anti-HCV have chronic hepatitis C regardless of their serum alanine aminotransferase levels. Donors with normal alanine aminotransferase levels and no HCV RNA in their serum generally have normal liver histologic findings or minimal changes and have probably recovered from HCV infection. C1 NIH,LIVER DIS SECT,BETHESDA,MD 20892. CTR DIS CONTROL & PREVENT,ATLANTA,GA. OI Kleiner, David/0000-0003-3442-4453 NR 38 TC 218 Z9 226 U1 0 U2 1 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 SEP 1 PY 1995 VL 123 IS 5 BP 330 EP 337 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA RQ988 UT WOS:A1995RQ98800002 PM 7542854 ER PT J AU HEYSE, SP TILLEY, BC ALARCON, GS AF HEYSE, SP TILLEY, BC ALARCON, GS TI MINOCYCLINE IN RHEUMATOID-ARTHRITIS - RESPONSE SO ANNALS OF INTERNAL MEDICINE LA English DT Letter ID CLINICAL-TRIALS C1 HENRY FORD HLTH SCI CTR,DETROIT,MI 48202. UNIV ALABAMA,BIRMINGHAM,AL 35294. RP HEYSE, SP (reprint author), NIAMSD,BETHESDA,MD 20892, USA. NR 4 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 SEP 1 PY 1995 VL 123 IS 5 BP 392 EP 392 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA RQ988 UT WOS:A1995RQ98800018 ER PT J AU JAFFE, ES AF JAFFE, ES TI ANGIOIMMUNOBLASTIC T-CELL LYMPHOMA - NEW INSIGHTS, BUT THE CLINICAL CHALLENGE REMAINS SO ANNALS OF ONCOLOGY LA English DT Editorial Material ID ANGIO-IMMUNOBLASTIC LYMPHADENOPATHY; DYSPROTEINEMIA; CLASSIFICATION; DISORDERS; FEATURES RP JAFFE, ES (reprint author), NCI,HEMATOPATHOL SECT,PATHOL LAB,BETHESDA,MD 20892, USA. NR 21 TC 14 Z9 15 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 1995 VL 6 IS 7 BP 631 EP 632 PG 2 WC Oncology SC Oncology GA TA129 UT WOS:A1995TA12900006 PM 8664181 ER PT J AU GESELOWITZ, DA NECKERS, LM AF GESELOWITZ, DA NECKERS, LM TI BOVINE SERUM-ALBUMIN IS A MAJOR OLIGONUCLEOTIDE-BINDING PROTEIN FOUND ON THE SURFACE OF CULTURED-CELLS SO ANTISENSE RESEARCH AND DEVELOPMENT LA English DT Note ID RECEPTOR-MEDIATED ENDOCYTOSIS; IN-VIVO; INTERNALIZATION; DNA; RAT AB To better understand the uptake of oligonucleotides into cells, we have studied the labeling of cell surface proteins by an oligonucleotide conjugated to a radiolabeled photoactivatable crosslinker (Denny-Jaffe reagent). When HL60 cells are treated with the conjugate for 2 hours in a medium containing bovine serum albumin (BSA), almost all of the cell-associated label is found in one protein, which we identify as BSA. Cells grown and treated in a serum-free medium do not show this protein, whereas it is plainly seen in cells that are grown in serum-containing medium but then treated in serum-free medium. Overall association of the oligonucleotide with cells is much higher in serum-free medium than in BSA-containing medium, but the oligonucleotide is mostly not protein-associated in the absence of BSA. We conclude that (1) BSA from the medium serves to block overall association of oligonucleotide with cells, and (2) BSA is the main cell surface protein binding oligonucleotides. We discuss the possible role of albumin in endocytic uptake of oligonucleotides in the cell and in the biodistribution of oligonucleotides in vivo. C1 NIH,CTR CLIN,DEPT NUCL MED,BETHESDA,MD 20892. NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NR 23 TC 37 Z9 40 U1 1 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1050-5261 J9 ANTISENSE RES DEV JI Antisense Res. Dev. PD FAL PY 1995 VL 5 IS 3 BP 213 EP 217 PG 5 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA RX488 UT WOS:A1995RX48800006 PM 8785477 ER PT J AU CHOKEKIJCHAI, S SHIRASAKA, T WEINSTEIN, JN MITSUYA, H AF CHOKEKIJCHAI, S SHIRASAKA, T WEINSTEIN, JN MITSUYA, H TI IN-VITRO ANTI-HIV-1 ACTIVITY OF HIV PROTEASE INHIBITOR KNI-272 IN RESTING AND ACTIVATED CELLS - IMPLICATIONS FOR ITS COMBINED USE WITH AZT OR DDI SO ANTIVIRAL RESEARCH LA English DT Article DE ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS); ANTIVIRAL THERAPY; AZIDOTHYMIDINE; DIDEOXYINOSINE; PROTEASE INHIBITOR; COMBINATION THERAPY ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS-RELATED COMPLEX; REVERSE-TRANSCRIPTASE; TYPE-1 REPLICATION; DRUG-COMBINATIONS; ZIDOVUDINE AZT; INVITRO; THERAPY; AZIDOTHYMIDINE; INFECTION AB KNI-272, a conformationally constrained human immunodeficiency virus (HIV) protease inhibitor containing a P1 allophenylnorstatine (Apns) ((2S,3S)- 3-amino-2-hydroxy-4-phenylbutyric acid), has been shown to be a selective and potent inhibitor of the replication of a wide spectrum of HIV strains in vitro. When KNI-272 was tested in combination with 3'-azido-2',3'-dideoxythymidine (AZT) or 2',3'-dideoxyinosine (ddI) against a primary HIV-1 isolate in phytohemagglutinin-activated peripheral blood mononuclear cells (PHA-PBM), its activity was identified to be additive, but not synergistic or antagonistic, as analyzed with the COMBO program package. When tested alone for anti-HIV-1 activity in resting PBM (R-PBM) and PHA-PBM, KNI-272 was found to be comparably potent against the virus in both target cell populations, whereas AZT was more potent in PHA-PBM than in R-PBM and ddI was more potent in R-PBM. These data suggest a potential clinical application of KNI-272 and its analogs. C1 NCI,MED BRANCH,EXPTL RETROVIROL SECT,BETHESDA,MD 20892. NCI,THEORET IMMUNOL SECT,MATH BIOL LAB,BETHESDA,MD 20892. NR 35 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD SEP PY 1995 VL 28 IS 1 BP 25 EP 38 DI 10.1016/0166-3542(95)00036-L PG 14 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA RV195 UT WOS:A1995RV19500003 PM 8585758 ER PT J AU YADLOWSKY, MJ SCHMITT, JM BONNER, RF AF YADLOWSKY, MJ SCHMITT, JM BONNER, RF TI MULTIPLE-SCATTERING IN OPTICAL COHERENCE MICROSCOPY SO APPLIED OPTICS LA English DT Article ID REFLECTOMETRY; SYSTEMS AB We show that the multiple-scatter rejection provided by optical coherence microscopy (low-coherence interferometry) can be incomplete in optically turbid media and that multiple scattering manifests itself in two distinct ways. Multiple small-angle scattering results in an effective probe field that is stronger than expected from a first-order beam extinction model, but that contains a distorted wave front that enhances the apparent reflectance of small structures relative to those that are larger than the unscattered incident beam. Multiple wide-angle scattering produces a broad diffuse haze that reduces the contrast of subsequent features. C1 NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RP YADLOWSKY, MJ (reprint author), CORNING INC,DIV SCI & TECHNOL,CORNING,NY 14831, USA. RI Bonner, Robert/C-6783-2015 NR 16 TC 99 Z9 101 U1 1 U2 8 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 SN 0003-6935 J9 APPL OPTICS JI Appl. Optics PD SEP 1 PY 1995 VL 34 IS 25 BP 5699 EP 5707 PG 9 WC Optics SC Optics GA RR044 UT WOS:A1995RR04400020 PM 21060400 ER PT J AU COWDRY, RW JENSEN, PS AF COWDRY, RW JENSEN, PS TI GRADING THE PROGRESS OF CHILD AND ADOLESCENT MENTAL-HEALTH RESEARCH - NIMH PERSPECTIVES SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Editorial Material RP COWDRY, RW (reprint author), NIMH,5600 FISHERS LN,ROCKVILLE,MD 20857, USA. OI Jensen, Peter/0000-0003-2387-0650 NR 5 TC 1 Z9 1 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD SEP PY 1995 VL 52 IS 9 BP 732 EP 734 PG 3 WC Psychiatry SC Psychiatry GA RU139 UT WOS:A1995RU13900005 PM 7654124 ER PT J AU MYERS, AH MICHELSON, JD VANNATTA, M COX, Q JINNAH, R AF MYERS, AH MICHELSON, JD VANNATTA, M COX, Q JINNAH, R TI PREVENTION OF HIP-FRACTURES IN THE ELDERLY - RECEPTIVITY TO PROTECTIVE GARMENTS SO ARCHIVES OF GERONTOLOGY AND GERIATRICS LA English DT Article DE ELDERLY; ENERGY-ABSORPTION; HIP FRACTURES; PREVENTION; PROTECTIVE GARMENT; RECEPTIVITY ID FEASIBILITY; HEALTH; CARE AB A case study was undertaken to determine perceptions about protective garments for the prevention of recurrent hip fractures, We studied 169 patients with hip fractures, over 50 years of age, who were admitted to four university-affiliate hospitals. Proxy respondents were interviewed for 36% (n = 61) of the patients, Significant differences were found in the two groups; therefore, only the analyses from 108 patients who were interviewed are reported. Seventy percent of the patients were willing to wear a padded garment prescribed by a doctor. Factors associated with a positive response were no previous hip fracture, and an intrinsic cause of the fracture (P less than or equal to 0.05), Over half (55%) of the patients were willing to wear an inflatable garment. Being female and fracturing the hip away from home were two factors that were associated with a positive response. Characteristics of the protective garment that patients thought were a concern or very important were effectiveness (83%), fit (82%), comfort (78%), laundering (66%), cost (57%), not showing (55%) and looked well (54%). These findings may assist investigators in the design of protective garments and thereby increase the receptivity and compliance among elderly patients. C1 JOHNS HOPKINS UNIV, SCH MED, JOHNS HOPKINS OUTPATIENT CTR, DEPT ORTHOPAED SURG, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, CTR CLIN TRIALS, BALTIMORE, MD 21205 USA. LEICESTER UNIV HOSP, DEPT ORTHOPAED, LEICESTER, LEICS, ENGLAND. JOHNS HOPKINS UNIV, DEPT ORTHOPAED SURG, BALTIMORE, MD 21228 USA. RP MYERS, AH (reprint author), NIA, GERONTOL RES CTR, BEHAV SCI LAB, 4940 EASTERN AVE, BALTIMORE, MD 21224 USA. OI Michelson, James/0000-0001-6997-2666 NR 31 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0167-4943 J9 ARCH GERONTOL GERIAT JI Arch. Gerontol. Geriatr. PD SEP-OCT PY 1995 VL 21 IS 2 BP 179 EP 189 DI 10.1016/0167-4943(95)00637-Z PG 11 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA RW599 UT WOS:A1995RW59900006 PM 15374213 ER PT J AU LESKE, MC WU, SY HYMAN, L SPERDUTO, R UNDERWOOD, B CHYLACK, LT MILTON, RC SRIVASTAVA, S ANSARI, N AF LESKE, MC WU, SY HYMAN, L SPERDUTO, R UNDERWOOD, B CHYLACK, LT MILTON, RC SRIVASTAVA, S ANSARI, N TI BIOCHEMICAL FACTORS IN THE LENS OPACITIES CASE-CONTROL STUDY SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID EPIDEMIOLOGIC ASSOCIATIONS; RISK-FACTORS; CATARACT; EPITHELIUM; NUCLEAR; PLASMA AB Objective: To evaluate associations with biochemical indicators of nutritional and other risk factors in the Lens Opacities Case-Control Study. Design: Case-control study. Setting and Participants: The Lens Opacities Case-Control Study determined risk factors for cortical, nuclear, and posterior subcapsular opacities among 1380 participants aged 40 to 79 years. Delta Collection: Vitamin E, selenium, and biochemistry profile determinations were performed on all patients; red blood cell enzymes and amino acids were measured in systematic samples of about 25% of the Lens Opacities Case-Control Study population. Outcome: Laboratory test values in cases and controls were compared and expressed as odds ratios and 95% confidence intervals. Results: In polychotomous logistic regression analyses controlling for age and sex, the risk of opacities was reduced to less than one half in persons with higher levels of vitamin E (odds ratio, 0.44 for nuclear opacities), albumin-globulin ratio (odds ratio, 0.41 for mixed opacities), or iron (odds ratio, 0.43 for cortical opacities); higher uric acid levels increased risk (odds ratio, 1.74 for mixed opacities). Persons with opacities were twice as likely to have high glutathione reductase activity (with flavin adenine dinucleotide), which suggests low riboflavin status (odds ratio, 2.13). Most odds ratios for amino acids were under unity and were significantly decreased for glycine (0.36) and aspartic acid (0.31). Conclusions: Lens opacities were associated with lower levels of riboflavin, vitamin E, iron, and protein nutritional status. Higher levels of uric acid increased risk of mixed opacities. The findings for riboflavin, vitamin E, iron, and uric acid are compatible with the dietary intake and medical history results of the Lens Opacities Case-Control Study. C1 NEI, OFF BIOMETRY & EPIDEMIOL, BETHESDA, MD 20892 USA. WHO, CH-1211 GENEVA, SWITZERLAND. HARVARD UNIV, SCH MED, DEPT OPHTHALMOL, BOSTON, MA USA. BRIGHAM & WOMENS HOSP, DEPT SURG, DIV OPHTHALMOL, BOSTON, MA 02115 USA. UNIV TEXAS, MED BRANCH, DEPT HUMAN BIOL CHEM & GENET, GALVESTON, TX 77550 USA. RP SUNY STONY BROOK, DEPT PREVENT MED, DIV EPIDEMIOL, HSC L3 099, STONY BROOK, NY 11794 USA. FU NEI NIH HHS [EYO5733] NR 42 TC 80 Z9 82 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-9950 EI 1538-3601 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD SEP PY 1995 VL 113 IS 9 BP 1113 EP 1119 PG 7 WC Ophthalmology SC Ophthalmology GA RT421 UT WOS:A1995RT42100014 PM 7661743 ER PT J AU ROTH, MJ MEDEIROS, LJ ELENITOBAJOHNSON, K KUCHNIO, M JAFFE, ES STETLERSTEVENSON, M AF ROTH, MJ MEDEIROS, LJ ELENITOBAJOHNSON, K KUCHNIO, M JAFFE, ES STETLERSTEVENSON, M TI EXTRAMEDULLARY MYELOID CELL TUMORS - AN IMMUNOHISTOCHEMICAL STUDY OF 29 CASES USING ROUTINELY FIXED AND PROCESSED PARAFFIN-EMBEDDED TISSUE-SECTIONS SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID GRANULOCYTIC SARCOMA; LEUKEMIA; EXPRESSION; DIAGNOSIS; MUTATIONS; PROTEIN AB Objective.-Extramedullary myeloid cell tumors (EMCTs) may be unsuspected clinically and difficult to recognize histologically. Fresh or frozen tissue is often not available for analysis. We studied 29 cases of EMCT using routinely fixed and processed paraffin-embedded tissue, an immunohistochemical method, and a panel of antibodies. Patients.-We studied 29 patients with EMCTs: 22 males and 7 females, with a median age of 48 years (range, 5 to 80 years). Histologically, 9 tumors were well differentiated, 16 were poorly differentiated, and 4 were blastic. Results.-The Leder stain (napthol-ASD-chloroacetate esterase) was positive in 21 (77.7%) of 27 tumors. Immunohistochemically, the following antibodies reacted with the greatest number of cases: Leu-22 or MT1 (CD43) in 28 (96.6%) of 29, antilysozyme in 27 (96.4%) of 28, and antimyeloperoxidase (MP07) in 21 (91.3%) of 23 cases. Other myeloid lineage-associated antibodies were positive in a subset of cases: antineutrophil elastase (NP57) in 10 (62.5%) of 16, Leu-M1 (CD15) in 7 (46.6%) of 15, and Mac-387 in 6 (40.0%) of 15 cases. The well-differentiated EMCTs reacted with most myeloid-associated antibodies; poorly differentiated and blastic tumors were more often negative. The pan-leukocyte antibody LCA (CD45RB) reacted with 15 (60%) of 25 neoplasms. Three (16.6%) of 18 tumors contained numerous p53-positive cells, ranging from 10% to 50% of the tumor cell population, In 10 cases, exons 5 through 8 of the p53 gene were analyzed using the polymerase chain reaction and single-stranded conformational polymorphism analysis. Gel shifts consistent with mutations were identified in exon 8 of one tumor (10%) that exhibited abundant p53 immunostaining. Conclusions.-lmmunohistochemical studies using fixed, paraffin-embedded sections are very useful in the diagnosis of EMCTs. The most sensitive antibodies are anti-CD43, antilysozyme, and antimyeloperoxidase. Immunohistochemical methods are more sensitive than the Leder stain. We found p53 staining in a small subset of cases, in which we were able to confirm evidence of p53 gene mutation using the polymerase chain reaction and single-stranded conformational polymorphism analysis in one case; p53 gene mutations appear to be uncommon in EMCTs. C1 RHODE ISL HOSP,DEPT PATHOL,PROVIDENCE,RI 02902. BROWN UNIV,SCH MED,PROVIDENCE,RI 02912. RP ROTH, MJ (reprint author), NCI,PATHOL LAB,10 CTR DR,BLDG 10,ROOM 2A19,BETHESDA,MD 20892, USA. NR 26 TC 65 Z9 67 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD SEP PY 1995 VL 119 IS 9 BP 790 EP 798 PG 9 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA RU153 UT WOS:A1995RU15300007 PM 7668936 ER PT J AU BIJUR, PE TRUMBLE, A HAREL, Y OVERPECK, MD JONES, D SCHEIDT, PC AF BIJUR, PE TRUMBLE, A HAREL, Y OVERPECK, MD JONES, D SCHEIDT, PC TI SPORTS AND RECREATION INJURIES IN US CHILDREN AND ADOLESCENTS SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID EPIDEMIOLOGY; PREVENTION; FOOTBALL AB Objectives: To estimate and describe morbidity from sports and recreation injuries in children and adolescents. Design: Survey conducted by the National Center for Health Statistics-the Child Health Supplement to the 1988 National Health interview Survey. Setting: The general community. Participants: Representative sample of the noninstitutionalized civilian US population. Five percent of the eligible households did not participate. The subject of this report is 11840 children and adolescents aged 5 to 17 years. Main Outcome Measures: Medically attended nonfatal injuries resulting from sports and recreation, and serious sports injuries, defined as injuries resulting in hospitalization, surgical treatment, missed school, or half a day or more in bed. Sports and recreation injuries were defined as those occurring in a place of recreation or sports, or receiving any of the following International Classification of Diseases, Ninth Revision (ICD-9) E-codes: struck in sports, fall in sports, bicycle-related injury, riding an animal, water sports, overexertion, fall from playground equipment or other vehicles, primarily skates and skateboards. Results: The estimated annual number of all injuries from sports and recreation in US children and adolescents is 4 379 000 (95% confidence interval = 3 147 000 to 5 611 000); from serious sport injuries, 1 363 000 (95% confidence interval = 632 000 to 2 095 000). Sports account for 36% of injuries from all causes. Cause and nature of injury are strongly related to age. Sports do not account for a disproportionate number of serious or repeated injuries compared with other causes of injuries. Conclusion: Sports activities account for a large number and substantial proportion of all injuries to children and youth. C1 ALBERT EINSTEIN COLL MED,DEPT EPIDEMIOL & SOCIAL MED,BRONX,NY 10467. NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,ROCKVILLE,MD. BAR ILAN UNIV,GRAD PROGRAM MED SOCIOL,RAMAT GAN,ISRAEL. CTR DIS CONTROL,NATL CTR CHRON DIS PREVENT & HLTH PROMOT,ATLANTA,GA 30333. GEORGE WASHINGTON UNIV,SCH MED,DEPT PEDIAT,WASHINGTON,DC 20052. RP BIJUR, PE (reprint author), ALBERT EINSTEIN COLL MED,ROSE F KENNEDY CTR,DEPT PEDIAT,ROOM 920,1410 PELHAM PKWY S,BRONX,NY 10461, USA. FU NICHD NIH HHS [R01-HD25416-02] NR 21 TC 100 Z9 103 U1 1 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD SEP PY 1995 VL 149 IS 9 BP 1009 EP 1016 PG 8 WC Pediatrics SC Pediatrics GA RU136 UT WOS:A1995RU13600010 PM 7655585 ER PT J AU TRACY, RP BOVILL, EG YANEZ, D PSATY, BM FRIED, LP HEISS, G LEE, M POLAK, JF SAVAGE, PJ AF TRACY, RP BOVILL, EG YANEZ, D PSATY, BM FRIED, LP HEISS, G LEE, M POLAK, JF SAVAGE, PJ TI FIBRINOGEN AND FACTOR-VIII, BUT NOT FACTOR-VII, ARE ASSOCIATED WITH MEASURES OF SUBCLINICAL CARDIOVASCULAR-DISEASE IN THE ELDERLY - RESULTS FROM THE CARDIOVASCULAR HEALTH STUDY SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE CARDIOVASCULAR DISEASE; BLOOD COAGULATION; FACTORS; ELDERLY; RISK FACTORS ID PLASMA FACTOR-VII; ACUTE CORONARY SYNDROMES; ISCHEMIC-HEART-DISEASE; MYOCARDIAL-INFARCTION; RISK FACTOR; DEGRADATION PRODUCTS; HEMOSTATIC FUNCTION; ARTERIAL-DISEASE; BLOOD-VISCOSITY; ATHEROSCLEROSIS AB No studies have examined the associations of coagulation factor levels with measures of subclinical cardiovascular disease (CVD) in the elderly. The Cardiovascular Health Study (CHS) is a prospective, population-based cohort study of CVD in persons older than 65 years. At the baseline examination, we measured fibrinogen, factor VII, and factor VIII levels in 5024 of the 5201 participants of the CHS and examined the associations of these coagulation factors with measures of subclinical CVD in a cross-sectional analysis. Subclinical CVD measures were based on electrocardiography, carotid ultrasonography, echocardiography, and ankle-arm blood pressure measurements (AAI). For analyses, we used the full cohort as well as two mutually exclusive subgroups: those with prevalent clinical CVD at baseline and those without. Fibrinogen and to a lesser extent factor VIII showed positive associations with a variety of subclinical CVD measures. In age-adjusted analyses, fibrinogen and factor VIII were significantly associated with 8 of 10 measures. In multivariate analyses, and AAI. Factor VIII was associated with abnormal wall motion and AAI in the full cohort only. Factor VII was not consistently associated with subclinical disease measures. In bivariate analyses that included data from all three groups, there were 5 positive subclinical disease associations and 5 negative associations for factor VII. In multivariate analyses, there were no significant associations between factor VII and subclinical CVD in the full cohort or in either subgroup. We conclude that in these cross-sectional analyses, fibrinogen and to a lesser extent factor VIII are associated with subclinical CVD in the elderly, even in those without symptoms or a history of clinical CVD. Factor VII, however, was not associated with subclinical CVD in the elderly. C1 UNIV VERMONT,DEPT BIOCHEM,COLCHESTER,VT 05446. UNIV WASHINGTON,DEPT BIOSTAT,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98195. JOHNS HOPKINS UNIV,DEPT MED,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,DEPT EPIDEMIOL,BALTIMORE,MD 21218. UNIV N CAROLINA,DEPT EPIDEMIOL,CHAPEL HILL,NC 27599. UNIV CALIF DAVIS,DEPT MED,DAVIS,CA 95616. BRIGHAM & WOMENS HOSP,DEPT RADIOL,BOSTON,MA 02115. NHLBI,EPIDEMIOL & BIOMETRY PROGRAM,BETHESDA,MD 20892. UNIV WASHINGTON,DEPT EPIDEMIOL,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT HLTH SERV,SEATTLE,WA 98195. RP TRACY, RP (reprint author), UNIV VERMONT,DEPT PATHOL,AQUATEC BLDG,ROMM T205,55A S PK DR,COLCHESTER,VT 05446, USA. FU NHLBI NIH HHS [N01-HC-85081, N01-HC-85079, N01-HC-85080] NR 70 TC 80 Z9 81 U1 1 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscl. Thromb. Vasc. Biol. PD SEP PY 1995 VL 15 IS 9 BP 1269 EP 1279 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA RV120 UT WOS:A1995RV12000002 PM 7670938 ER PT J AU CID, MC ESPARZA, J MORALES, D MCGOWEN, KA GRANT, DG URBANOMARQUEZ, A SCHAPER, HW HOFFMAN, GS KLEINMAN, HK AF CID, MC ESPARZA, J MORALES, D MCGOWEN, KA GRANT, DG URBANOMARQUEZ, A SCHAPER, HW HOFFMAN, GS KLEINMAN, HK TI ESTRADIOL ENHANCES ENDOTHELIAL-CELL, ATTACHMENT TO EXTRACELLULAR-MATRIX PROTEINS THROUGH AN INCREASE IN INTEGRIN EXPRESSION SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 HOSP CLIN BARCELONA,E-08035 BARCELONA,SPAIN. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL 60611. CLEVELAND CLIN FDN,CLEVELAND,OH 44195. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 16 EP 16 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68400016 ER PT J AU ADAMS, EM DOHLMAN, J EIDELMAN, G PLOTZ, PH AF ADAMS, EM DOHLMAN, J EIDELMAN, G PLOTZ, PH TI THE CYTOKINES OF MUSCLE IN MYOSITIS - THE PREDOMINANCE OF MIP-1-ALPHA SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,ARTHRIT RHEUMATISM BRANCH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 87 EP 87 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68400087 ER PT J AU MOUNTZ, JD PIERSON, MC ZHOU, T CHENG, J ELKON, KB HASUNUMA, T NISHIOKA, K OKUMURA, K LIN, A SONG, GG DALE, JK GORLEY, M STRAUS, SE AF MOUNTZ, JD PIERSON, MC ZHOU, T CHENG, J ELKON, KB HASUNUMA, T NISHIOKA, K OKUMURA, K LIN, A SONG, GG DALE, JK GORLEY, M STRAUS, SE TI SFAS EXPRESSION IN PATIENTS WITH AUTOIMMUNE-DISEASE SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV ALABAMA,BIRMINGHAM,AL 35294. VET ADM MED CTR,BIRMINGHAM,AL. CORNELL UNIV,NEW YORK,NY 10021. ST MARIANNA UNIV,KAWASAKI,KANAGAWA,JAPAN. JUNTENDO UNIV,KAWASAKI,KANAGAWA,JAPAN. NCI,BETHESDA,MD 20892. KOREA UNIV,SEOUL 136701,SOUTH KOREA. NIAID,BETHESDA,MD 20892. NIAMS,BETHESDA,MD 20892. RI Hasunuma, Tomoko/F-3533-2011 NR 0 TC 2 Z9 2 U1 1 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 127 EP 127 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68400127 ER PT J AU ZAGARIYA, A BIRRER, M MUNGRE, S LOVIS, R POPE, R AF ZAGARIYA, A BIRRER, M MUNGRE, S LOVIS, R POPE, R TI ACTIVATION OF TNF-ALPHA GENE-EXPRESSION BY NF-IL6 AND CJUN SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NORTHWESTERN UNIV,DEPT MED,DIV ARTHRIT,CHICAGO,IL 60611. LAKESIDE VET ADM MED CTR,CHICAGO,IL 60611. NCI,ROCKVILLE,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 161 EP 161 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68400161 ER PT J AU KATZ, P WHALEN, G KEHRL, JH KYRIAKIS, JH AF KATZ, P WHALEN, G KEHRL, JH KYRIAKIS, JH TI ACTIVATION OF THE STRESS-ACTIVATED PROTEIN-KINASE (SAPK) PATHWAY BY A NOVEL GERMINAL CENTER B-CELL KINASE SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02129. GEORGETOWN UNIV,WASHINGTON,DC 20007. NIAID,UR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 166 EP 166 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68400166 ER PT J AU LOVELL, DJ GIANNINI, EH RIDER, L HICKS, J SMITH, M RENNEBOHM, R LINDSLEY, C AF LOVELL, DJ GIANNINI, EH RIDER, L HICKS, J SMITH, M RENNEBOHM, R LINDSLEY, C TI VALIDATION AND RELIABILITY OF THE CHILDHOOD MYOSITIS ASSESSMENT SCALE (CMAS) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV CINCINNATI,CINCINNATI,OH 45229. NIH,BETHESDA,MD 20892. OHIO STATE UNIV,COLUMBUS,OH 43205. UNIV KANSAS,KANSAS CITY,KS 66103. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 186 EP 186 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68400186 ER PT J AU CHIKANZA, IC PETROU, P PANAYI, GS CHROUSOS, G AF CHIKANZA, IC PETROU, P PANAYI, GS CHROUSOS, G TI ARGININE-VASOPRESSIN (AVP) SECRETION IN RHEUMATOID-ARTHRITIS - PATHOPHYSIOLOGICAL IMPLICATIONS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV LONDON LONDON HOSP,INFLAMMAT GRP,LONDON E1 2AD,ENGLAND. GUYS HOSP,RHEUMATOL UNIT,LONDON,ENGLAND. NIH,BETHESDA,MD. ORSUGOZ RHEUMA,BUDAPEST,HUNGARY. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 382 EP 382 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68400382 ER PT J AU SAMMARITANO, L MAGID, M KAPLAN, C PETERSON, M LOCKSHIN, M AF SAMMARITANO, L MAGID, M KAPLAN, C PETERSON, M LOCKSHIN, M TI A PROSPECTIVE-STUDY OF CLINICAL-FEATURES AND PLACENTAL PATHOLOGY IN SYSTEMIC LUPUS-ERYTHEMATOSUS (SLE) WITH AND WITHOUT ANTIPHOSPHOLIPID ANTIBODIES (APL) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 CORNELL UNIV,HOSP SPECIAL SURG,MED CTR,NEW YORK,NY 10021. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 394 EP 394 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68400394 ER PT J AU PETRI, M ARAMLI, LA BALDWIN, MT KLEIN, NW KLEINMAN, HK AF PETRI, M ARAMLI, LA BALDWIN, MT KLEIN, NW KLEINMAN, HK TI ANTILAMININ ANTIBODIES IN LUPUS PREGNANCY SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. UNIV CONNECTICUT,CTR ENVIRONM HLTH,STORRS,CT 06269. NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 402 EP 402 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68400402 ER PT J AU LETHBRIDGECEIKU, M HOCHBERG, MC SCOTT, WW REICHLE, R PLATO, CC ROY, TA TOBIN, JD AF LETHBRIDGECEIKU, M HOCHBERG, MC SCOTT, WW REICHLE, R PLATO, CC ROY, TA TOBIN, JD TI LACK OF ASSOCIATION OF REPRODUCTION AND GYNECOLOGIC FACTORS WITH RADIOGRAPHIC FEATURES OF OSTEOARTHRITIS OF THE KNEE IN POSTMENOPAUSAL WOMEN - DATA FROM THE BALTIMORE LONGITUDINAL-STUDY OF AGING SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 426 EP 426 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68400426 ER PT J AU OSHEA, JJ KAWAMURA, M CHEN, YQ HANSEN, E TORTOLIANI, J REIDY, M BACON, C JOHNSTON, J AF OSHEA, JJ KAWAMURA, M CHEN, YQ HANSEN, E TORTOLIANI, J REIDY, M BACON, C JOHNSTON, J TI CYTOKINE SIGNAL-TRANSDUCTION - ROLE OF JAKS AND STATS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,ARTHRITIS & RHEUMATISM BRANCH,LEUKOCYTE CELL BIOL SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 488 EP 488 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68400487 ER PT J AU GERBER, LH AF GERBER, LH TI A REHABILITATION TRAINING-PROGRAM FOR RHEUMATOLOGY FELLOWS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 537 EP 537 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68400536 ER PT J AU LETHBRIDGECEJKU, M HOCHBERG, MC SCOTT, WW PLATO, CC TOBIN, JD AF LETHBRIDGECEJKU, M HOCHBERG, MC SCOTT, WW PLATO, CC TOBIN, JD TI LONGITUDINAL CHANGE IN JOINT SPACE OF THE KNEE - DATA FROM THE BALTIMORE LONGITUDINAL-STUDY ON AGING SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. NIA,CTR GERONTOL RES,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 652 EP 652 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68400651 ER PT J AU HIRSCH, R FERNANDES, RJ PILLEMER, SR HOCHBERG, MC LANE, NE ALTMAN, RD KNOWLER, WC BENNETT, PH AF HIRSCH, R FERNANDES, RJ PILLEMER, SR HOCHBERG, MC LANE, NE ALTMAN, RD KNOWLER, WC BENNETT, PH TI HIP OSTEOARTHRITIS IN THE PIMA-INDIANS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,BETHESDA,MD 20892. NIDDK,PHOENIX,AZ 85014. UNIV MARYLAND,BALTIMORE,MD 21201. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. UNIV MIAMI,MIAMI,FL 33101. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 655 EP 655 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68400654 ER PT J AU FESSLER, BJ YARBORO, CH KLIPPEL, JH HAMA, N WILDER, RL BOUMPAS, DT AF FESSLER, BJ YARBORO, CH KLIPPEL, JH HAMA, N WILDER, RL BOUMPAS, DT TI A PILOT-STUDY OF FLUDARABINE (FLU) IN REFRACTORY RHEUMATOID-ARTHRITIS (RA) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 776 EP 776 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68400775 ER PT J AU VOGLER, LB MCNICHOLL, J GAY, BB AF VOGLER, LB MCNICHOLL, J GAY, BB TI CLINICAL AND GENETIC EVALUATION OF A MIDDLE-EASTERN FAMILY WITH 5 OF 6 CHILDREN PRESENTING FEATURES OF SEVERE POLYARTICULAR JUVENILE RHEUMATOID-ARTHRITIS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 EMORY UNIV,ATLANTA,GA 30322. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30322. NIA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 798 EP 798 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68400797 ER PT J AU PANDO, JA YARBORO, C ELLABAN, A SAAIBI, S KANIK, K VILLALBA, L GERARD, H BRANIGAN, P HUDSON, A MENG, Z GOURLEY, MF KLIPPEL, JH SCHUMACHER, HR AF PANDO, JA YARBORO, C ELLABAN, A SAAIBI, S KANIK, K VILLALBA, L GERARD, H BRANIGAN, P HUDSON, A MENG, Z GOURLEY, MF KLIPPEL, JH SCHUMACHER, HR TI PREVALENCE OF CHLAMYDIA-TRACHOMATIS (CT) BY PCR IN THE SYNOVIUM OF PATIENTS WITH EARLY RHEUMATOID-ARTHRITIS (RA) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,BETHESDA,MD 20892. UNIV PENN,PHILADELPHIA,PA 19104. VET ADM MED CTR,PHILADELPHIA,PA 19104. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 805 EP 805 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68400804 ER PT J AU CROFFORD, LJ KALOGERAS, KT MASTORAKOS, G MAGIAKOU, MA WELLS, J KANIK, KS GOLD, PW CHROUSOS, GP WILDER, RL AF CROFFORD, LJ KALOGERAS, KT MASTORAKOS, G MAGIAKOU, MA WELLS, J KANIK, KS GOLD, PW CHROUSOS, GP WILDER, RL TI CIRCADIAN RELATIONSHIPS BETWEEN HYPOTHALAMIC-PITUITARY-ADRENAL AXIS HORMONES AND INTERLEUKIN-6 IN PATIENTS WITH EARLY UNTREATED RHEUMATOID-ARTHRITIS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV MICHIGAN,ANN ARBOR,MI 48109. NIH,BETHESDA,MD 20892. RI Crofford, Leslie/J-8010-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 819 EP 819 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68400818 ER PT J AU MITTLEMAN, BB SHEARER, GM PAYNE, S WOLF, S MOZES, E AF MITTLEMAN, BB SHEARER, GM PAYNE, S WOLF, S MOZES, E TI TREATMENT OF EXPERIMENTAL SLE WITH RECOMBINANT MURINE IL-12 SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 WEIZMANN INST SCI,IL-76100 REHOVOT,ISRAEL. GENET INST INC,CAMBRIDGE,MA 02140. NCI,EIB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 883 EP 883 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68400882 ER PT J AU SCOTT, D BALOW, J AUSTIN, H LARSON, A YARBORO, C BROWN, M FLEISHER, T KLIPPEL, J AF SCOTT, D BALOW, J AUSTIN, H LARSON, A YARBORO, C BROWN, M FLEISHER, T KLIPPEL, J TI A PILOT-STUDY OF CLADRIBINE (2'-CHLORODEOXYADENOSINE) IN LUPUS NEPHRITIS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 904 EP 904 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68400903 ER PT J AU VILLABA, ML HICKS, JE THORNTON, B BURGESS, S SHERMAN, J ADAMS, E LEFF, RL PLOTZ, PH MILLER, FW AF VILLABA, ML HICKS, JE THORNTON, B BURGESS, S SHERMAN, J ADAMS, E LEFF, RL PLOTZ, PH MILLER, FW TI A COMBINATION OF ORAL METHOTREXATE AND AZATHIOPRINE, (MTX/AZA) IS MORE EFFECTIVE THAN HIGH-DOSE INTRAVENOUS MTX WITH LEUCOVORIN RESCUE IN TREATMENT-RESISTANT MYOSITIS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,BETHESDA,MD 20892. NIH,CTR CLIN,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 925 EP 925 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68400924 ER PT J AU WILDER, RL GRIFFITHS, M REMMERS, E DU, Y OHARE, A LONGMAN, R AF WILDER, RL GRIFFITHS, M REMMERS, E DU, Y OHARE, A LONGMAN, R TI MAPPING OF CHROMOSOMAL REGIONS CONTROLLING SEVERITY OF COLLAGEN-INDUCED ARTHRITIS (CIA) IN RATS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. VET ADM MED CTR,SALT LAKE CITY,UT 84148. UNIV UTAH,SALT LAKE CITY,UT 84148. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 938 EP 938 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68400937 ER PT J AU KIEHL, M GOURLEY, M LEFKOWITH, JB AF KIEHL, M GOURLEY, M LEFKOWITH, JB TI GLOMERULAR BINDING-ANTIBODIES IN LUPUS NEPHRITIS PATIENTS - CHARACTERIZATION AND CLINICAL-SIGNIFICANCE SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV WASHINGTON,SCH MED,ST LOUIS,MO 63110. NIH,BETHESDA,MD 21921. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 966 EP 966 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68400965 ER PT J AU PANDO, JA YARBORO, C GOURLEY, MF GLUCK, V KLIPPEL, JH SCHUMACHER, HR AF PANDO, JA YARBORO, C GOURLEY, MF GLUCK, V KLIPPEL, JH SCHUMACHER, HR TI MORBIDITY AND PATIENT RESPONSE TO BLIND SYNOVIAL BIOPSIES USING A PARKER-PEARSON NEEDLE SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,BETHESDA,MD 20892. UNIV PENN,PHILADELPHIA,PA 19104. VAMC,PHILADELPHIA,PA 19104. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 1051 EP 1051 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68401050 ER PT J AU MARTIN, K LETHBRIDGECEIKU, M MULLER, D ELAHI, D ANDRES, R PLATO, C TOBIN, J HOCHBERG, M AF MARTIN, K LETHBRIDGECEIKU, M MULLER, D ELAHI, D ANDRES, R PLATO, C TOBIN, J HOCHBERG, M TI RISK-FACTORS FOR CARDIOVASCULAR-DISEASE AND RADIOGRAPHIC FEATURES OF KNEE OSTEOARTHRITIS - DATA FROM THE BALTIMORE LONGITUDINAL-STUDY OF AGING SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV MARYLAND,BALTIMORE,MD 21201. VET ADM MED CTR,GRECC,BALTIMORE,MD 21201. NIA,GRC,BALTIMORE,MD 21201. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 1131 EP 1131 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68401130 ER PT J AU SANSLONE, WR STARK, SP AF SANSLONE, WR STARK, SP TI ESTROGEN REPLACEMENT THERAPY AND FRACTURES - ECONOMIC-BENEFITS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 1135 EP 1135 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68401134 ER PT J AU FESSLER, BJ AUSTIN, HA KLIPPEL, JH VAUGHAN, EM BALOW, JE BOUMPAS, DT AF FESSLER, BJ AUSTIN, HA KLIPPEL, JH VAUGHAN, EM BALOW, JE BOUMPAS, DT TI PREDICTORS OF FAVORABLE LONG-TERM RENAL OUTCOME FOLLOWING INTENSIVE IMMUNOSUPPRESSIVE PULSE THERAPY FOR LUPUS NEPHRITIS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 1159 EP 1159 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68401158 ER PT J AU BRANIGAN, PJ GERARD, HC SAAIBI, D WILLIAMS, WV PANDO, J HUDSON, AP SCHUMACHER, HR AF BRANIGAN, PJ GERARD, HC SAAIBI, D WILLIAMS, WV PANDO, J HUDSON, AP SCHUMACHER, HR TI PCR SCREENING OF SYNOVIAL TISSUE VS FLUID FROM PATIENTS WITH REITERS-SYNDROME (RS) AND OTHER SPONDYLOARTHROPATHIES FOR CHLAMYDIA-TRACHOMATIS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,BETHESDA,MD 20892. UNIV PENN,SCH MED,DVA MED CTR,PHILADELPHIA,PA 19104. HAHNEMANN UNIV,COLL MED,PHILADELPHIA,PA 19104. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 1167 EP 1167 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68401166 ER PT J AU BENEVOLENSKAVA, LI BOYER, GS ERDESZ, S TEMPLIN, DW ALEXEEVA, LI LAWRENCE, RC KRYLOV, MY HEYSE, S MYLOV, NM CORNONIHUNTLEY, J EVERETT, D GORING, WP BOWLER, A AF BENEVOLENSKAVA, LI BOYER, GS ERDESZ, S TEMPLIN, DW ALEXEEVA, LI LAWRENCE, RC KRYLOV, MY HEYSE, S MYLOV, NM CORNONIHUNTLEY, J EVERETT, D GORING, WP BOWLER, A TI SPONDYLOARTHROPATHY (SPA) IN CIRCUMPOLAR POPULATIONS OF RUSSIA AND ALASKA SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMSD,BETHESDA,MD 20892. NEI,BETHESDA,MD 20892. DUKE UNIV,SCH PUBL HLTH,CHAPEL HILL,NC 27710. UNIV ARIZONA,TUCSON,AZ 85721. PROSPECT ASSOC,ROCKVILLE,MD 20852. RUSSIAN ACAD MED SCI,INST RHEUMATOL,DEPT EPIDEMIOL & GENET RHEUMAT DIS,MOSCOW 109801,RUSSIA. ALASKA AREA NATIVE HLTH SERV,ANCHORAGE,AK 99501. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 1172 EP 1172 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68401171 ER PT J AU KOTAKE, S SCHUMACHER, HR KANIK, KS PANDO, JA KLIPPEL, JH GOURLEY, MF YARBORO, CH WILDER, RL AF KOTAKE, S SCHUMACHER, HR KANIK, KS PANDO, JA KLIPPEL, JH GOURLEY, MF YARBORO, CH WILDER, RL TI TYPE1 AND TYPE2 CYTOKINE PROFILES IN SYNOVIUM FROM EARLY SYNOVITIS PATIENTS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,BETHESDA,MD 20892. UNIV PENN,PHILADELPHIA,PA 19104. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 1204 EP 1204 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68401203 ER PT J AU GOURLEY, M HERION, D GLUCK, V PANDO, J YARBORO, C KLIPPEL, J SALLIE, R AF GOURLEY, M HERION, D GLUCK, V PANDO, J YARBORO, C KLIPPEL, J SALLIE, R TI GENETIC AND METABOLIC MARKERS OF BONE-MINERAL DENSITY (BMD) IN SYSTEMIC LUPUS-ERYTHEMATOSUS (SLE) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 1230 EP 1230 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68401229 ER PT J AU WILDER, RL HANSEN, C DU, Y DING, YP GOLDMUNTZ, E KOTAKE, S GE, L MATHERN, P ZHA, HB REMMERS, EF AF WILDER, RL HANSEN, C DU, Y DING, YP GOLDMUNTZ, E KOTAKE, S GE, L MATHERN, P ZHA, HB REMMERS, EF TI CHROMOSOMAL MAPPING OF A DISTINCT OSTEOPETROSIS GENE (OP) IN THE RAT SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 1236 EP 1236 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68401235 ER PT J AU GRIFFITHS, MM CANNON, GW TERATO, K REMMERS, E WILDER, RL AF GRIFFITHS, MM CANNON, GW TERATO, K REMMERS, E WILDER, RL TI BACKGROUND GENE SUPPRESSION OF HOMOLOGOUS RAT TYPE-II COLLAGEN-INDUCED ARTHRITIS (RII-CIA) IN ACI RATS CARRYING THE RII-CIA SUSCEPTIBLE MAJOR HISTOCOMPATIBILITY (MHC) LOCUS - RT1(2) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV UTAH,VET ADM MED CTR,DIV RHEUMATOL,RES SERV,SALT LAKE CITY,UT 84148. NIAMS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 1307 EP 1307 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68401306 ER PT J AU EDBERG, WE DOW, JC CSERNOK, D SNELLER, E KEYSTONE, M GROSS, E HOFFMAN, W KIMBERLY, G AF EDBERG, WE DOW, JC CSERNOK, D SNELLER, E KEYSTONE, M GROSS, E HOFFMAN, W KIMBERLY, G TI FC-GAMMA-RHIB ALLELES ARE SIGNIFICANTLY SKEWED IN WEGENERS GRANULOMATOSIS (WG) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 CORNELL UNIV,HOSP SPECIAL SURG,MED CTR,NEW YORK,NY 10021. UNIV LUBECK,W-2400 LUBECK,GERMANY. WELLESLEY HOSP,TORONTO,ON,CANADA. NIH,BETHESDA,MD 20892. CLEVELAND CLIN FDN,CLEVELAND,OH 44195. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 1333 EP 1333 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68401332 ER PT J AU PILLEMER, SR MATTESON, EL JACOBSSON, LTH MARTENS, PB FOX, PC AF PILLEMER, SR MATTESON, EL JACOBSSON, LTH MARTENS, PB FOX, PC TI INCIDENCE OF SJOGRENS-SYNDROME IN OLMSTED COUNTY, MINNESOTA SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 MAYO CLIN,ROCHESTER,MN. NIH,BETHESDA,MD. LUND UNIV,MALMO,SWEDEN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 1340 EP 1340 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68401339 ER PT J AU LAWRENCE, RC PILLEMER, SR MURPHY, R OSTECHEGI, Y THOMA, G LONG, R BERMAN, LE AF LAWRENCE, RC PILLEMER, SR MURPHY, R OSTECHEGI, Y THOMA, G LONG, R BERMAN, LE TI INTERNET ACCESS TO A NATIONAL-POPULATION SAMPLE OF RADIOGRAPHIC IMAGES OF NECK AND LUMBAR SPINE SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,BETHESDA,MD 20892. CDC,HCHS,HYATTSVILLE,MD 20782. NIH,NATL LIB MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 1394 EP 1394 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68401392 ER PT J AU LANGFORD, CA SNELLER, MC HALLAHAN, CW HOFFMAN, GS KAMMERER, WA TALARWILLIAMS, C FAUCI, AS LEBOVICS, RS AF LANGFORD, CA SNELLER, MC HALLAHAN, CW HOFFMAN, GS KAMMERER, WA TALARWILLIAMS, C FAUCI, AS LEBOVICS, RS TI CLINICAL-FEATURES AND THERAPEUTIC MANAGEMENT OF SUBGLOTTIC STENOSIS IN PATIENTS WITH WEGENERS GRANULOMATOSIS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 1424 EP 1424 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68401422 ER PT J AU TALARWILLIAMS, C HIIAZI, Y WALTHER, M HALLAHAN, CW KERR, GS HOFFMAN, GS LUBENSKY, I FAUCI, AS SNELLER, MC AF TALARWILLIAMS, C HIIAZI, Y WALTHER, M HALLAHAN, CW KERR, GS HOFFMAN, GS LUBENSKY, I FAUCI, AS SNELLER, MC TI CYCLOPHOSPHAMIDE-INDUCED BLADDER TOXICITY IN PATIENTS WITH WEGENERS GRANULOMATOSIS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 1425 EP 1425 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68401423 ER PT J AU SABET, A BROOKS, WM SIBBITT, WL AF SABET, A BROOKS, WM SIBBITT, WL TI NEUROCHEMICAL QUANTIFICATION IN SYSTEMIC LUPUS-ERYTHEMATOSUS USING SPECTROSCOPIC IMAGING SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV NEW MEXICO,CTR NONINVAS DIAGNOSIS,ALBUQUERQUE,NM 87131. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. HENRY FORD HOSP,DETROIT,MI 48202. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 1430 EP 1430 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68401428 ER PT J AU GOURLEY, M AUSLIN, H YARBORO, C VAUGHAN, E MUIR, J LINDAHL, M BOUMOAS, D SCOTT, D KLIPPEL, J BALOW, J STEINBERG, A AF GOURLEY, M AUSLIN, H YARBORO, C VAUGHAN, E MUIR, J LINDAHL, M BOUMOAS, D SCOTT, D KLIPPEL, J BALOW, J STEINBERG, A TI RANDOMIZED TRIAL OF MULTIPLE BOLUSES OF METHYLPREDNISOLONE (MP) OR CYCLOPHOSPHAMIDE (CY) OR THE COMBINATION (CY/MP) IN PATIENTS WITH LUPUS NEPHRITIS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 1434 EP 1434 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68401432 ER PT J AU KANIK, KS CHROUSOS, GP YARBORO, CH SCHUMACHER, HR WILDER, RL AF KANIK, KS CHROUSOS, GP YARBORO, CH SCHUMACHER, HR WILDER, RL TI PITUITARY-ADRENAL HORMONAL ABNORMALITIES IN PATIENTS WITH NEW-ONSET SYNOVITIS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,BETHESDA,MD 20892. NICHHD,BETHESDA,MD 20892. VAMC,PHILADELPHIA,PA 19104. UNIV PENN,PHILADELPHIA,PA 19104. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 1453 EP 1453 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68401451 ER PT J AU SALMON, JE MILLARD, S SCHACHTER, L GINZLER, EM RAMSEYGOLDMAN, R GOURLEY, MF ARNETT, FC KIMBERLY, RP AF SALMON, JE MILLARD, S SCHACHTER, L GINZLER, EM RAMSEYGOLDMAN, R GOURLEY, MF ARNETT, FC KIMBERLY, RP TI FC-GAMMA-RIIA ALLELES ARE HERITABLE RISK-FACTORS FOR LUPUS NEPHRITIS IN AFRICAN-AMERICANS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 CORNELL UNIV,MED CTR,NEW YORK,NY 10021. SUNY HLTH SCI CTR,BROOKLYN,NY 11203. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL 60611. NIAMS,BETHESDA,MD 20892. UNIV TEXAS,HLTH SCI CTR,HOUSTON,TX 77225. CORNELL UNIV,MED CTR,NEW YORK,NY 10021. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 1470 EP 1470 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68401468 ER PT J AU NAKABAVASHI, T DANG, H KONG, L GAISER, A LETTERIO, J TALAL, N AF NAKABAVASHI, T DANG, H KONG, L GAISER, A LETTERIO, J TALAL, N TI UP-REGULATION OF CYTOKINE GENE AND ADHESION MOLECULE PROTEIN EXPRESSION IN THE SALIVARY-GLANDS OF TGF-BETA-1 NULL MICE SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 1496 EP 1496 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68401494 ER PT J AU PATTATUCCI, AML HAMER, DH AF PATTATUCCI, AML HAMER, DH TI DEVELOPMENT AND FAMILIALITY OF SEXUAL ORIENTATION IN FEMALES SO BEHAVIOR GENETICS LA English DT Article DE HOMOSEXUALITY; LESBIAN; BISEXUAL; SEXUAL ORIENTATION; FAMILIALITY; DEVELOPMENT; HEREDITY ID CONGENITAL ADRENAL-HYPERPLASIA; GENDER-RELATED BEHAVIOR; MALE HOMOSEXUALITY; BISEXUAL WOMEN; IDENTITY; TWINS; CHROMOSOME; ATTITUDES; CHILDREN AB The development and familial clustering of sexual orientation were studied in 358 heterosexual, bisexual, and homosexual women. Sexual orientation, as measured by the Kinsey scales, was diverse yet showed statistical congruity and stability over a 1- to 1.5-year time span. Developmental patterns, as measured by retrospective reports on the ages of first sexual or romantic attraction and of self-acknowledgment of sexual orientation, were very similar in the heterosexual and lesbian subjects except for the difference in object choice. The bisexual subjects displayed intermediate patterns that were more similar to the heterosexuals' on most facets yet closer to the lesbian subjects' on other dimensions. Familial clustering of nonheterosexual orientation was significant. Using two criteria, elevated rates of nonheterosexuality were found in four classes of relatives: sisters, daughters, nieces, and female cousins through a paternal uncle. The current data are not sufficient to distinguish between genetic and shared environmental sources of this familial aggregation. We discuss the possibility of using developmental criteria to differentiate between inherited and cultural sources of variation in female sexual orientation. RP PATTATUCCI, AML (reprint author), NCI,BLDG 37,ROOM 4A13,BETHESDA,MD 20892, USA. NR 37 TC 60 Z9 61 U1 1 U2 21 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD SEP PY 1995 VL 25 IS 5 BP 407 EP 420 DI 10.1007/BF02253370 PG 14 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA RW362 UT WOS:A1995RW36200001 PM 7487838 ER PT J AU LALAND, KN KUMM, J VANHORN, JD FELDMAN, MW AF LALAND, KN KUMM, J VANHORN, JD FELDMAN, MW TI A GENE-CULTURE MODEL OF HUMAN HANDEDNESS SO BEHAVIOR GENETICS LA English DT Article DE HANDEDNESS; ASYMMETRY; GENETIC; CULTURAL TRANSMISSION; MATHEMATICAL MODEL; EVOLUTION ID HAND PREFERENCE; TRANSMISSION; DEXTRALITY; POPULATION AB A model of handedness incorporating both genetic and cultural processes is proposed, based on an evolutionary analysis, and maximum-likelihood estimates of its parameters are generated. This model has the characteristics that (i) no genetic variation underlies variation in handedness, and (ii) variation in handedness among humans is the result of a combination of cultural and developmental factors, but (iii) a genetic influence remains since handedness is a facultative trait. The model fits the data from 17 studies of handedness in families and 14 studies of handedness in monozygotic and dizygotic twins. This model has the additional advantages that it can explain why monozygotic and dizygotic twins and siblings have similar concordance rates, and no hypothetical selection regimes are required to explain the persistence of left handedness. C1 STANFORD UNIV,DEPT BIOL SCI,STANFORD,CA 94305. NIH,BETHESDA,MD 20892. RP LALAND, KN (reprint author), UNIV CAMBRIDGE,SUBDEPT ANIM BEHAV,CAMBRIDGE CB3 8AA,ENGLAND. RI Laland, Kevin /C-9482-2011 NR 48 TC 74 Z9 75 U1 0 U2 5 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD SEP PY 1995 VL 25 IS 5 BP 433 EP 445 DI 10.1007/BF02253372 PG 13 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA RW362 UT WOS:A1995RW36200003 PM 7487840 ER PT J AU BOINSKI, S CAMPBELL, AF AF BOINSKI, S CAMPBELL, AF TI USE OF TRILL VOCALIZATIONS TO COORDINATE TROOP MOVEMENT AMONG WHITE-FACED CAPUCHINS - A 2ND FIELD-TEST SO BEHAVIOUR LA English DT Article ID FEMALE SQUIRREL-MONKEYS; CEBUS-CAPUCINUS; VOCAL BEHAVIOR; VERVET MONKEYS; COMMUNICATION; RESPONSES; CALL AB The white-faced capuchin, Cebus capucinus, employed a specialized vocalization, the trill, to coordinate troop movement at La Selva, an Atlantic wet-forest study site in Costa Rica. We analyse the contexts in which this intra-group vocalization was emitted, including responses elicited from other group members. A cumulative 26.6 hours of continuous samples and 3,314 spectrograms (including 1,295 trills) were analysed from a study troop with 16 focal subjects. These results generally corroborate the conclusions of a comparable field study of T white-faced capuchins at Santa Rosa, a Pacific coast dry-forest site in Costa Rica(BOINSKI, 1993, Amer. J. Primatol. 30, p. 85-100). At both sites, (1) trills were closely associated with the initiation of movement by a stationary troop in a specific direction. (2) Trills were emitted at a much higher rate in the leading edge of a travelling troop than in following positions. (3) Individuals often reinforced the efforts of other troop members to coordinate troop movement. (4) Lack of consensus among troop members over the travel route was evident. (5) In rare instances trills were employed in tactical maneuvers suggestive of intentionality and the ability to anticipate behavioural effects. Differences in the usage of trills at these two sites were also detected. (1) At La Selva all troop members, with the exception of infants, used trills in the coordination of troop movement, whereas at Santa Rosa marked age, sex and rank distinctions in the extent of participation were apparent. (2) Capuchins at Santa Rosa altered the trajectory of travelling troops with trills, even reversing directions, but not at La Selva. These disparities may follow from differences between the sites in the extent of visual and auditory contact typical among troop members, social structure, susceptibility to predation, and possible genetic variation. C1 UNIV FLORIDA,DIV COMPARAT MED,GAINESVILLE,FL 32611. NICHHD,COMPARAT ETHOL LAB,BETHESDA,MD 20892. WASHINGTON UNIV,DEPT ANTHROPOL,ST LOUIS,MO 63130. RP BOINSKI, S (reprint author), UNIV FLORIDA,DEPT ANTHROPOL,1350 TURLINGTON,GAINESVILLE,FL 32611, USA. NR 69 TC 58 Z9 59 U1 1 U2 18 PU E J BRILL PI LEIDEN PA PO BOX 9000, 2300 PA LEIDEN, NETHERLANDS SN 0005-7959 J9 BEHAVIOUR JI Behaviour PD SEP PY 1995 VL 132 BP 875 EP 901 DI 10.1163/156853995X00054 PN 11-12 PG 27 WC Behavioral Sciences; Zoology SC Behavioral Sciences; Zoology GA TH731 UT WOS:A1995TH73100005 ER PT J AU GONZALES, C AF GONZALES, C TI THE BIRTH AND THE SUCCESS OF MBRS SO BIO-TECHNOLOGY LA English DT Note RP GONZALES, C (reprint author), NIH,MBRS PROGRAM,BLDG 45,SUITE 2AS37,45 CTR DR,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 0733-222X J9 BIO-TECHNOL JI Bio-Technology PD SEP PY 1995 VL 13 IS 9 BP 961 EP 961 DI 10.1038/nbt0995-961 PG 1 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA RR316 UT WOS:A1995RR31600017 ER PT J AU Pant, HC Veeranna AF Pant, HC Veeranna TI Neurofilament phosphorylation SO BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE LA English DT Article; Proceedings Paper CT 5th Fisher Winternational Symposium of the Canadian-Society-for-Cellular-and-Molecular-Biology - Cytoskeleton in Health and Disease CY MAR 09-12, 1995 CL MANOIR DU LAC DELAGE, CANADA SP Canadian Soc Cellular & Molec Biol DE neurofilament proteins; phosphorylation; kinases; phosphatases; regulators; inhibitors; multimesic complex; domains ID NEURONAL INTERMEDIATE FILAMENTS; DEPENDENT PROTEIN-KINASE; HELICAL HEAD DOMAIN; BOVINE SPINAL-CORD; NF-L; AXONAL-TRANSPORT; MAMMALIAN NEUROFILAMENTS; CDC2-LIKE KINASE; TRANSGENIC MICE; CDC2 KINASE AB Neurofilament proteins (NFPs) are highly phosphorylated molecules in the axonal compartment of the adult nervous system. The phosphorylation of NFP is considered an important determinant of filament caliber, plasticity, and stability. This process reflects the function of NFs during the lifetime of a neuron from differentiation in the embryo through long-term activity in the adult until aging and environmental insult leads to pathology and ultimately death. NF function is modulated by phosphorylation-dephosphorylation in each of these diverse neuronal states. In this review we have summarized some of these properties of NFP in adult nervous tissue, mostly from work in our own laboratory. Identification of sites phosphorylated in vivo in high molecular weight NFP (NF-H) and properties of NF-associated and neural-specific kinases phosphorylating specific sites in NFP are described. A model to explain the role of NF phosphorylation in determining filament caliber, plasticity, and stability is proposed. RP Pant, HC (reprint author), NINCDS,NIH,DIV INTRAMURAL RES,NEUROCHEM LAB,BETHESDA,MD 20892, USA. NR 84 TC 154 Z9 154 U1 0 U2 1 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0829-8211 J9 BIOCHEM CELL BIOL JI Biochem. Cell Biol. PD SEP-OCT PY 1995 VL 73 IS 9-10 BP 575 EP 592 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TV592 UT WOS:A1995TV59200001 PM 8714676 ER PT J AU PITCHER, C ROBERTS, L FAWELL, S ZDANOVSKY, AG FITZGERALD, DJ LORD, JM AF PITCHER, C ROBERTS, L FAWELL, S ZDANOVSKY, AG FITZGERALD, DJ LORD, JM TI GENERATION OF A POTENT CHIMERIC TOXIN BY REPLACEMENT OF DOMAIN-III OF PSEUDOMONAS EXOTOXIN WITH RICIN-A CHAIN KDEL SO BIOCONJUGATE CHEMISTRY LA English DT Article ID A-CHAIN; MAMMALIAN-CELLS; MONOCLONAL-ANTIBODIES; CYTOTOXIC ACTIVITY; ESCHERICHIA-COLI; DIPHTHERIA-TOXIN; LETHAL FACTOR; AERUGINOSA; PROTEIN; POLYPEPTIDES AB Following cellular uptake, Pseudomonas exotoxin (PE) is cleaved by cellular protease which generates an enzymatically active C-terminal fragment (amino acids 280-613). This 37 kD fragment translocates to the cell cytosol where it ADP-ribosylates elongation factor 2 and inhibits protein synthesis. A recombinant hybrid toxin (designated PE-RTA) in which the ADP-ribosylation domain (domain III) was replaced by the RNA N-glycosidase domain of ricin (the A chain or RTA) has been produced in E. coli. The hybrid toxin effectively and specifically depurinated 28S ribosomal. RNA, indicating that the ricin A moiety folded into its native conformation. The cytotoxicity of PE-RTA for L929 cells was approximately 100-fold less than either native PE or whole ricin. However, the addition of the tetrapeptide KDEL to the C-terminus of PE-RTA (producing PE-RTA KDEL) increased cytotoxicity to the level of the native toxins. By analogy to PE, both PE-RTA and PE-RTA KDEL would be proteolytically cleaved within PE domain II during cell entry. A single amino acid substitution, believed to disrupt an essential step in the transport of the catalytically active PE fragment to the cell cytosol (Trp281 to Ala: Zdanovsky, A. G., Chiron, M., Pastan, I., and FitzGerald, D. J. (1993) J. Biol. Chem. 268, 21791-21799), reduced the cytotoxicities of both PE and PE-RTA KDEL by approximately 100-fold. Taken together, these data show that the ricin A chain component of the hybrid toxin requires essential PE-derived sequences at both the N- and C-termini of the translocating fragment. Clearly, in the context of this fusion protein, ricin A chain cannot effect its own transfer to the cytosol. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. UNIV WARWICK,DEPT BIOL SCI,COVENTRY CV4 7AL,W MIDLANDS,ENGLAND. BIOGEN INC,CAMBRIDGE,MA 02142. NR 38 TC 6 Z9 6 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD SEP-OCT PY 1995 VL 6 IS 5 BP 624 EP 629 DI 10.1021/bc00035a018 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA RY634 UT WOS:A1995RY63400018 PM 8974463 ER PT J AU ROSENBERG, PS AF ROSENBERG, PS TI HAZARD FUNCTION ESTIMATION USING B-SPLINES SO BIOMETRICS LA English DT Article DE CENSORED SURVIVAL DATA; HAZARD FUNCTION ESTIMATION; SPLINES; MAXIMUM LIKELIHOOD ESTIMATION; AIDS; HIV INFECTION INCIDENCE ID REGRESSION-MODELS; SURVIVAL-DATA; KAPLAN-MEIER; AIDS AB A flexible parametric procedure is given to model the hazard function as a linear combination of cubic B-splines and to obtain maximum likelihood estimates from censored survival data. The approach yields smooth estimates of the hazard and survivorship functions that are intermediate in structure between strongly parametric and non-parametric models. A simple method is described for selecting the number and location of knots. Simulation results show favorable root mean square error compared to cion-parametric estimates for both the hazard and survivorship functions. Three methods are given to calculate confidence intervals based on the delta method, profile likelihood, and bootstrap, respectively. The procedure is applied to estimate hazard rates for acquired immunodeficiency syndrome (AIDS) following infection with human immunodeficiency virus (HIV). Spline methods can accommodate complex censoring mechanisms such as those that arise in the AIDS setting. To illustrate, HIV infection incidence is estimated for a cohort of hemophiliacs in which the dates of HIV infection are interval-censored and some subjects were born after the onset of the HIV epidemic. RP ROSENBERG, PS (reprint author), NCI,EPIDEMIOL METHODS SECT,ROCKVILLE,MD 20852, USA. NR 22 TC 77 Z9 77 U1 1 U2 17 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 1995 VL 51 IS 3 BP 874 EP 887 DI 10.2307/2532989 PG 14 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA RW742 UT WOS:A1995RW74200008 PM 7548706 ER PT J AU BAKER, SG AF BAKER, SG TI MARGINAL REGRESSION FOR REPEATED BINARY DATA WITH OUTCOME SUBJECT TO NON-IGNORABLE NONRESPONSE SO BIOMETRICS LA English DT Article DE NON-IGNORABLE; NONRESPONSE ID MISSING CATEGORICAL-DATA; LOG-LINEAR MODELS; NONIGNORABLE NONRESPONSE; MAXIMUM-LIKELIHOOD; LONGITUDINAL DATA; INCOMPLETE DATA; RANDOM DROPOUTS; VARIABLES; CHILDREN; DISCRETE AB Using a model that accounts for non-ignorable non-response, we analyzed data from the Muscatine Risk Factor Study (Woolson and Clarke, 1984, Journal of the Royal Statistical Society, Ser-ies A 147, 87-99) on the effects of gender and age on obesity in schoolchildren, The methodology is related to that of Diggle and Kenward (1994, Applied Statistics 43, 49-93), except that the repeated data are binary, not continuous, and the non-response occurs in various patterns, not just dropouts. We found strong evidence that non-response was non-ignorable. In addition, we found that the proportion of children who were obese differed significantly with gender and increased with age. RP BAKER, SG (reprint author), NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,BETHESDA,MD 20892, USA. NR 58 TC 61 Z9 62 U1 1 U2 3 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 1995 VL 51 IS 3 BP 1042 EP 1052 DI 10.2307/2533003 PG 11 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA RW742 UT WOS:A1995RW74200022 PM 7548689 ER PT J AU LI, YX RINZEL, J VERGARA, L STOJILKOVIC, SS AF LI, YX RINZEL, J VERGARA, L STOJILKOVIC, SS TI SPONTANEOUS ELECTRICAL AND CALCIUM OSCILLATIONS IN UNSTIMULATED PITUITARY GONADOTROPHS SO BIOPHYSICAL JOURNAL LA English DT Article ID RAT ANTERIOR-PITUITARY; ACTION-POTENTIALS; PROLACTIN SECRETION; POTASSIUM CHANNELS; CA2+ OSCILLATIONS; CELL-LINE; CURRENTS; TRANSIENTS; NEURON; INFLUX AB Single pituitary cells often fire spontaneous action potentials (APs), which are believed to underlie spiking fluctuations in cytosolic calcium concentration ([Ca2+](i)). To address how these basal [Ca2+](i) fluctuations depend on changes in plasma membrane voltage (V), simultaneous measurements of V and [Ca2+](i) were performed in rat pituitary gonadotrophs. The data show that each [Ca2+](i) spike is produced by the Ca2+ entry during a single AP. Using these and previously obtained patch-clamp data, we develop a quantitative mathematical model of this plasma membrane oscillator and the accompanying spatiotemporal [Ca2+](i) oscillations. The model demonstrates that AP-induced [Ca2+](i) spiking is prominent only in a thin shell layer neighboring the cell surface. This localized [Ca2+](i) spike transiently activates the Ca2+-dependent K+ current resulting in a sharp afterhyperpolarization following each voltage spike. In accord with experimental observations, the model shows that the frequency and amplitude of the voltage spikes are highly sensitive to current injection and to the blocking of the Ca2+-sensitive current. Computations also predict that, leaving the membrane channels intact, the firing rate can be modified by changing the Ca2+ handling parameters: the Ca2+ diffusion rate, the Ca2+ buffering capacity, and the plasma membrane Ca2+ pump rate. Finally, the model suggests reasons that spontaneous APs were seen in some gonadotrophs but not in others. This model provides a basis for further exploring how plasma membrane electrical activity is involved in the control of cytosolic calcium level in unstimulated as well as agonist-stimulated gonadotrophs. C1 NIDDK,CELL BIOL & GENET LAB,BETHESDA,MD 20814. NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. RP LI, YX (reprint author), NIDDK,MATH RES BRANCH,9190 WISCONSIN AVE,SUITE 350,BETHESDA,MD 20814, USA. NR 45 TC 44 Z9 44 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 1995 VL 69 IS 3 BP 785 EP 795 PG 11 WC Biophysics SC Biophysics GA RZ852 UT WOS:A1995RZ85200006 PM 8519979 ER PT J AU CHERNOMORDIK, L CHANTURIYA, A GREEN, J ZIMMERBERG, J AF CHERNOMORDIK, L CHANTURIYA, A GREEN, J ZIMMERBERG, J TI THE HEMIFUSION INTERMEDIATE AND ITS CONVERSION TO COMPLETE FUSION - REGULATION BY MEMBRANE-COMPOSITION SO BIOPHYSICAL JOURNAL LA English DT Article ID PLANAR BILAYER-MEMBRANES; PHASE-TRANSITION TEMPERATURE; PHOSPHOLIPID-VESICLES; PHOSPHATIDYLETHANOLAMINE LIPOSOMES; FATTY-ACIDS; LYSOPHOSPHATIDYLCHOLINE; CHANNELS; DESTABILIZATION; FLUORESCENCE; MONOLAYERS AB To fuse, membranes must bend. The energy of each lipid monolayer with respect to bending is minimized at the spontaneous curvature of the monolayer. Two lipids known to promote opposite spontaneous curvatures, lysophosphatidylcholine and arachidonic acid, were added to different sides of planar phospholipid membranes. Lysophosphatidylcholine added to the contacting monolayers of fusing membranes inhibited the hemifusion we observed between lipid vesicles and planar membranes. In contrast, fusion pore formation depended upon the distal monolayer of the planar membrane; lysophosphatidylcholine promoted and arachidonic acid inhibited. Thus, the intermediates of hemifusion and fusion pores in phospholipid membranes involve different membrane monolayers and may have opposite net curvatures. Biological fusion may proceed through similar intermediates. RP CHERNOMORDIK, L (reprint author), NICHHD,THEORET & PHYS BIOL LAB,BLDG 10,RM 10D-04A,BETHESDA,MD 20892, USA. RI Wunder, Stephanie/B-5066-2012; Zdilla, Michael/B-4145-2011 NR 53 TC 173 Z9 176 U1 2 U2 14 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 1995 VL 69 IS 3 BP 922 EP 929 PG 8 WC Biophysics SC Biophysics GA RZ852 UT WOS:A1995RZ85200019 PM 8519992 ER PT J AU RAGHUNATHAN, G MILES, HT SASISEKHARAN, V AF RAGHUNATHAN, G MILES, HT SASISEKHARAN, V TI SYMMETRY AND STRUCTURE OF RNA AND DNA TRIPLE HELICES SO BIOPOLYMERS LA English DT Article ID STRANDED POLYNUCLEOTIDES; D(T)N.D(A)N.D(T)N AB Despite wide interest in nucleic acid triple helices, there has been no stereochemically satisfactory structure of an RNA triple helix in atomic detail. An RNA triplex structure has previously been proposed based on fiber diffraction and molecular modeling [S. Arnott and P.J. Bond (1973) Nature New Biology, Vol. 244, pp. 99-101; S. Arnott, P.J. Bond, E. Selsing, and P.J.C. Smith (1976) Nucleic Acids Research, Vol. 3, pp. 2459-2470], but it has not nonallowed close contacts at every triplet and is therefore not stereochemically acceptable. We propose here a new model fro an RNA triple helix in which the three chains have identical backbone conformations and are symmetry related. There are no short contacts. The modeling employs a novel geometrical approach using the linked atom least squares [P.J.C. Smith and S. Arnott (1978) Acta Crystallographica, Vol A34, pp. 3-11] program and is not based on energy minimization. In general, the method leads to a rang of possible structures rather than a unique structure. In the present case, however, the constraints resulting from the introduction of a third strand limit the possible structures to a very small range of conformation space. This method was used previously to obtain a model for DNA triple helices [G. Raghunathan, H.T. Miles, and V. Sasisekharan (1993) Biochemistry, Vol. 32, pp. 455-462], subsequently confirmed by fiber-type x-ray diffraction of oligomeric crystals [K. Liu, H.T. Miles, K.D. Parris, and V. Sasisekharan (1994) Nature Structural Biology, Vol. 1, pp. 11-12]. The above triple helices have Watson-Crick-Hoogsteen [K. Hoogsteen (1963) Acta Crystallographica, Vol. 16, pp. 907-916] pairing of the three bases. The same modeling method was used to investigate the feasibility of three-dimensional structures based on the three possible alternative hydrogen-bonding schemes: Watson-Crick-reverse Hoogsteen, Donohue [J. Donohue (1953) Proceedings of the National Academy of Science USA, Vol. 39, pp. 470-475] (reverse Watson-Crick)-Hoogsteen, and Donohue-reverse Hoogsteen. We found that none of these can occur in either RNA or DNA helices because they give rise only to structures with prohibitively short contacts between backbone and base atoms in the same chain. (C) 1995 John Wiley and Sons, Inc. C1 NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. RP RAGHUNATHAN, G (reprint author), NCI,MATH BIOL LAB,BLDG 12B,ROOM B116,BETHESDA,MD 20892, USA. NR 25 TC 14 Z9 15 U1 3 U2 6 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD SEP PY 1995 VL 36 IS 3 BP 333 EP 343 DI 10.1002/bip.360360308 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RP450 UT WOS:A1995RP45000007 PM 7545446 ER PT J AU CARROLL, MW MOSS, B AF CARROLL, MW MOSS, B TI ESCHERICHIA-COLI BETA-GLUCURONIDASE (GUS) AS A MARKER FOR RECOMBINANT VACCINIA VIRUSES SO BIOTECHNIQUES LA English DT Note ID GENE; EXPRESSION; SELECTION; VECTOR C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NR 15 TC 65 Z9 66 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD SEP PY 1995 VL 19 IS 3 BP 352 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RU448 UT WOS:A1995RU44800009 PM 7495543 ER PT J AU LACORAZZA, HD JENDOUBI, M AF LACORAZZA, HD JENDOUBI, M TI IN-SITU ASSESSMENT OF BETA-HEXOSAMINIDASE ACTIVITY SO BIOTECHNIQUES LA English DT Note C1 NEI,IMMUNOL LAB,GENET & MOLEC IMMUNOL SECT,BETHESDA,MD 20892. NR 8 TC 14 Z9 14 U1 2 U2 3 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD SEP PY 1995 VL 19 IS 3 BP 434 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RU448 UT WOS:A1995RU44800023 PM 7495557 ER PT J AU KELLER, JR ORTIZ, M RUSCETTI, FW AF KELLER, JR ORTIZ, M RUSCETTI, FW TI STEEL FACTOR (C-KIT LIGAND) PROMOTES THE SURVIVAL OF HEMATOPOIETIC STEM PROGENITOR CELLS IN THE ABSENCE OF CELL-DIVISION SO BLOOD LA English DT Article ID GROWTH-FACTOR; STROMAL CELLS; INVITRO; PROLIFERATION; CYCLE; TRANSMEMBRANE; REQUIREMENT; RECEPTOR; CULTURE AB It is known that the majority of primitive hematopoietic progenitors are in a noncycling quiescent state. In addition, normal hematopoietic progenitors and progenitor cell lines show an absolute dependence on growth factors for their survival in vitro, yet the effect of growth factors on progenitor cell survival has not been separated from effects on both proliferation and differentiation. Using an in vitro assay system, we examined whether growth factors could promote the survival of stem cells in culture in the absence of cell division. These studies show that steel factor (SLF) and, to a lesser extent, interleukin-3 (IL-3) directly promoted the survival of elutriated bone marrow progenitor cells (countercurrent centrifugal elutriation [CCE]-27) that are enriched for primitive hematopoietic progenitors that respond to the combination of SLF plus IL-3. Furthermore, SLF promoted the survival of short-term reconstituting cells (STRC), and long-term reconstituting cells (LTRC) with trilineage reconstitution potential in vivo. In comparison, granulocyte colony-stimulating factor (G-CSF), IL-6, leukemia inhibitory factor, IL-11, IL-1, granulocyte macrophage CSF (GM-CSF), and macrophage CSF (M-CSF) had no effect on the survival of these cells. In the presence of mitotic inhibitors (nocodazole or aphidicolin), SLF promoted the survival of CCE-27 progenitor cells that respond to the combination of SLF plus IL-3 in vitro and STRCs and LTRCs that are detected in vivo. Taken together, these data show that SLF can directly promote the survival of hematopoietic progenitor cells in the absence of cell division. This is a US government work. There are no restrictions on its use. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,LEUKOCYTE BIOL LAB,FREDERICK,MD 21702. RP KELLER, JR (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,POB B,FREDERICK,MD 21702, USA. NR 23 TC 96 Z9 98 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 1995 VL 86 IS 5 BP 1757 EP 1764 PG 8 WC Hematology SC Hematology GA RT386 UT WOS:A1995RT38600013 PM 7544641 ER PT J AU MURPHY, WJ FUNAKOSHI, S BECKWITH, M RUSHING, SE CONLEY, DK ARMITAGE, RJ FANSLOW, WC RAGER, HC TAUB, DD RUSCETTI, FW LONGO, DL AF MURPHY, WJ FUNAKOSHI, S BECKWITH, M RUSHING, SE CONLEY, DK ARMITAGE, RJ FANSLOW, WC RAGER, HC TAUB, DD RUSCETTI, FW LONGO, DL TI ANTIBODIES TO CD40 PREVENT EPSTEIN-BARR VIRUS-MEDIATED HUMAN B-CELL LYMPHOMAGENESIS IN SEVERE COMBINED IMMUNE-DEFICIENT MICE GIVEN HUMAN PERIPHERAL-BLOOD LYMPHOCYTES SO BLOOD LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; GROWTH-INHIBITION; LYMPHOPROLIFERATIVE DISEASE; TYROSINE PHOSPHORYLATION; ACTIVATION; ANTIGEN; RECEPTOR; PATHOGENESIS; CYTOKINES; APOPTOSIS AB CD40 is expressed on both normal and neoplastic B lymphocytes. Signal transduction through CD40 in vitro has been shown to exert stimulatory effects on normal B cells and inhibitory effects on Epstein-Barr virus (EBV)-induced B-cell lymphoma lines and some other cell lines derived from patients with aggressive histology lymphoma. The transfer of normal human peripheral blood lymphocytes (huPBL) from EBV-seropositive donors into severe combined immune deficient (SCID) mice has been previously shown to result in the generation of human B-cell lymphomas. These tumors are similar to the highly aggressive EBV-induced lymphomas that can arise clinically after transplantation or in the setting of immunodeficiency. Treatment of huPBL-SCID chimeric mice with anti-CD40 or anti-CD20 monoclonal antibodies (MoAb) significantly delayed the development of EBV-induced B-cell lymphoma. However, the effects of the two MoAb were mechanistically distinct. Anti-CD40 treatment prevented lymphoma generation, while still allowing for functional human B-cell engraftment in the huPBL-SCID mice compared with mice receiving no treatment, all of which succumbed to lymphoma. By contrast, treatment with anti-CD20 significantly inhibited total human B-cell engraftment in the SCID recipients, which accounted for the absence of lymphomas. In vitro assays examining the transformation of human B cells by EBV also indicated that anti-CD40 could directly inhibit EBV-transformation, whereas anti-CD20 antibodies had no effect. Thus, anti-CD40 exerts selective effects to allow for the engraftment of normal human B cells and prevent the emergence of EBV lymphomas. Stimulation of CD40 by antibodies or its physiologic ligand may, therefore, be of significant clinical use in the prevention of EBV-induced B lymphomas that may arise when EBV-seropositive individuals receive immunosuppressive regimens after transplantation or in immune deficiency states, such as acquired immune deficiency syndrome. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,CLIN SERV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. RP MURPHY, WJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702, USA. NR 28 TC 37 Z9 36 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 1995 VL 86 IS 5 BP 1946 EP 1953 PG 8 WC Hematology SC Hematology GA RT386 UT WOS:A1995RT38600036 PM 7544649 ER PT J AU MUSSO, T BADOLATO, R LONGO, DL GUSELLA, GL VARESIO, L AF MUSSO, T BADOLATO, R LONGO, DL GUSELLA, GL VARESIO, L TI LEUKEMIA INHIBITORY FACTOR INDUCES INTERLEUKIN-8 AND MONOCYTE CHEMOTACTIC AND ACTIVATING FACTOR IN HUMAN MONOCYTES - DIFFERENTIAL REGULATION BY INTERFERON-GAMMA SO BLOOD LA English DT Article ID IFN-GAMMA; CHEMOATTRACTANT PROTEIN-1; HUMAN FIBROBLASTS; GENE-EXPRESSION; CYTOKINE; CELLS; IL-2; RECEPTORS AB Leukemia inhibitory factor (LIF) is a cytokine released at the site of injuries where there is a recruitment of monocytes and polymorphonuclear cells. We analyzed the effect of LIF on human monocytes, which are a major source of chemotactic factors. We showed that supernatants of monocytes treated with LIF (50 ng/mL) for 18 hours had chemotactic activity for neutrophils and monocytes that was neutralized by anti-interleukin-8 (anti-IL-8) and anti-monocyte chemotactic and activating factor (anti-MCAF) neutralizing antibodies. Northern blot analysis showed induction of IL-8 and MCAF RNA in monocytes treated with LIF. Both IL-8 MCAF mRNA were induced within 3 hours of stimulation. IL-8 and MCAF mRNAs expression peaked at 6 hours and 18 hours, respectively. Interferon-gamma (IFN-gamma), a potent monocyte activator, inhibited IL-8 induction by LIF. On the contrary, IFN-gamma by itself induced MCAF and did not affect the LIF-induced MCAF. These results indicate that LIF released at the site of injury by inducing IL-8 and MCAF can play an important role in recruiting leukocytes and that IFN-gamma can differentially regulate this recruitment. C1 NCI,FREDERICK CANC RES & DEV CTR,OFF ASSOCIATE DIRECTOR,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. RP MUSSO, T (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,BLDG 560,FREDERICK,MD 21702, USA. RI Badolato, Raffaele/A-8081-2010; varesio, luigi/J-8261-2016 OI Badolato, Raffaele/0000-0001-7375-5410; varesio, luigi/0000-0001-5659-2218 NR 39 TC 30 Z9 30 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 1995 VL 86 IS 5 BP 1961 EP 1967 PG 7 WC Hematology SC Hematology GA RT386 UT WOS:A1995RT38600038 PM 7655023 ER PT J AU BROWN, KE YOUNG, NS AF BROWN, KE YOUNG, NS TI PARVOVIRUS B19 INFECTION AND HEMATOPOIESIS SO BLOOD REVIEWS LA English DT Review ID SICKLE-CELL-ANEMIA; VIRUS; B19-PARVOVIRUS; INVITRO; APLASIA; CRISIS AB Parvovirus B19, the only known human pathogenic parvovirus, is highly tropic to human bone marrow and replicates only in erythroid progenitor cells. The basis of this erythroid tropism is the tissue distribution of the B19 cellular receptor, globoside (blood group P antigen). In individuals with underlying hemolytic disorders, infection with parvovirus B19 is the primary cause of transient aplastic crisis (TAG). In immunocompromised patients, persistent B19 infection may develop that manifests as pure red cell aplasia and chronic anemia, B19 infection in utero can result in fetal death, hydrops fetalis, or congenital anemia. Diagnosis is based on examination of the bone marrow and B19 virological studies. Treatment of persistent infection with immunoglobulin leads to a rapid marked resolution of the anemia. RP BROWN, KE (reprint author), NHLBI,HEMATOL BRANCH,BLDG 10,ROOM 7CZ18,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 30 TC 65 Z9 66 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0268-960X J9 BLOOD REV JI Blood Rev. PD SEP PY 1995 VL 9 IS 3 BP 176 EP 182 DI 10.1016/0268-960X(95)90023-3 PG 7 WC Hematology SC Hematology GA TB194 UT WOS:A1995TB19400004 PM 8563519 ER PT J AU NORMANNO, N KIM, N WEN, DZ SMITH, K HARRIS, AL PLOWMAN, G COLLETTA, G CIARDIELLO, F SALOMON, DS AF NORMANNO, N KIM, N WEN, DZ SMITH, K HARRIS, AL PLOWMAN, G COLLETTA, G CIARDIELLO, F SALOMON, DS TI EXPRESSION OF MESSENGER-RNA FOR AMPHIREGULIN, HEREGULIN, AND CRIPTO-1, 3 NEW MEMBERS OF THE EPIDERMAL GROWTH-FACTOR FAMILY, IN HUMAN BREAST CARCINOMAS SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Note DE BREAST CANCER; AMPHIREGULIN; HEREGULIN; CRIPTO-1; EGF RECEPTOR FAMILY ID CANCER AB The expression of amphiregulin (AR), heregulin (HRG), and cripto-1 (CR-1) mRNA transcripts was assessed in 60 human primary breast carcinoma. AR and HRG transcripts were expressed respectively in 58% and 25% of the carcinomas as measured by Northern blot analysis. CR-1 mRNA was found in 77% of the carcinomas using Reverse Transcriptase-PCR analysis. Coexpression of two or three of these peptides was observed in several specimens. There was no significant association between AR, HRG, and CR-1 expression and nodal status, EGF receptor, or c-erbB-2 protooncogene expression in these tumors. However, a significant association between AR expression and estrogen receptor positivity was observed. C1 NCI,LTIB,TUMOR GROWTH FACTORS SECT,BETHESDA,MD 20892. AMGEN INC,THOUSAND OAKS,CA 91320. UNIV OXFORD,IMPERIAL CANC RES FUND,MOLEC ONCOL LABS,OXFORD OX3 7LJ,ENGLAND. BRISTOL MYER PHARMACEUT RES INST,SEATTLE,WA 98121. UNIV CHIETI,FAC MED & CHIRURG,IST PATOL UMANA & MED SOCIALE,I-66100 CHIETI,ITALY. UNIV NAPLES FEDERICO II,FAC MED & CHIRURG,CATTEDRA ONCOL MED,I-80131 NAPLES,ITALY. RP NORMANNO, N (reprint author), FDN PASCALE,IST NAZL STUDIO & CURA TUMORI,SERV ONCOL SPERIMENTALE D,I-80131 NAPLES,ITALY. RI PLOWMAN, Greg/E-2012-2011; OI Normanno, Nicola/0000-0002-7158-2605 NR 10 TC 72 Z9 73 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD SEP PY 1995 VL 35 IS 3 BP 293 EP 297 DI 10.1007/BF00665981 PG 5 WC Oncology SC Oncology GA RF037 UT WOS:A1995RF03700008 PM 7579500 ER PT J AU ISSARAGRISIL, S KAUFMAN, DW ANDERSON, TE CHANSUNG, K THAMPRASIT, T SIRIJIRACHAI, J PIANKIJAGUM, A PORAPAKHAM, Y VANNASAENG, S LEAVERTON, PE SHAPIRO, S YOUNG, NS SOMPRADEEKUL, S VUTHIVATANAKUL, T SRIRATANASATAVORN, C YARNCHAROEN, C LAEWSIRI, P KITTIMONGCOLPORN, S TEPMONGCOL, K WONGKONGDEJ, R VEJJAPINAND, R KIATVIRAKUL, V KARENG, K INTARAGUMTHORNCHAI, T CHANCHARUNEE, S SUVATTE, V SUPRADIT, P LAOHAVINIJ, S CHINARAT, V PRAYOONWIWAT, V ANGKURAVORAKUL, S ATICHARTKARN, V CHUANSAMRIT, A CHUTIPONG, S HATHIRAT, P ISARANKURA, P JETSRISUPARB, A JOOTAR, S KIATKACHORNTADA, N LAOSOMBAT, V LEKHAKUL, A MAKORNKAEWKAYOON, V NITIYANANT, P SEKSAN, P SONAKUL, D SRICHAIKUL, T SRIPAISAL, T SUCHARITCHAN, P SUKPANICHNAND, S SUKPANICHNAND, SY SUWANWELA, N TANTECHANURAK, C TANYAVUDH, K WATANANUKUL, P AF ISSARAGRISIL, S KAUFMAN, DW ANDERSON, TE CHANSUNG, K THAMPRASIT, T SIRIJIRACHAI, J PIANKIJAGUM, A PORAPAKHAM, Y VANNASAENG, S LEAVERTON, PE SHAPIRO, S YOUNG, NS SOMPRADEEKUL, S VUTHIVATANAKUL, T SRIRATANASATAVORN, C YARNCHAROEN, C LAEWSIRI, P KITTIMONGCOLPORN, S TEPMONGCOL, K WONGKONGDEJ, R VEJJAPINAND, R KIATVIRAKUL, V KARENG, K INTARAGUMTHORNCHAI, T CHANCHARUNEE, S SUVATTE, V SUPRADIT, P LAOHAVINIJ, S CHINARAT, V PRAYOONWIWAT, V ANGKURAVORAKUL, S ATICHARTKARN, V CHUANSAMRIT, A CHUTIPONG, S HATHIRAT, P ISARANKURA, P JETSRISUPARB, A JOOTAR, S KIATKACHORNTADA, N LAOSOMBAT, V LEKHAKUL, A MAKORNKAEWKAYOON, V NITIYANANT, P SEKSAN, P SONAKUL, D SRICHAIKUL, T SRIPAISAL, T SUCHARITCHAN, P SUKPANICHNAND, S SUKPANICHNAND, SY SUWANWELA, N TANTECHANURAK, C TANYAVUDH, K WATANANUKUL, P TI AN ASSOCIATION OF APLASTIC-ANEMIA IN THAILAND WITH LOW SOCIOECONOMIC-STATUS SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE APLASTIC ANEMIA; ETIOLOGY; SOCIOECONOMIC STATUS; EPIDEMIOLOGY; THAILAND ID ANEMIA AB The relationship of socioeconomic status to the risk of aplastic anaemia was evaluated in a case-control study conducted in Bangkok and two rural regions of Thailand (Khonkaen and Songkla). Among 152 cases and 921 controls there were significant trends of increasing risk with decreasing years of education (P = 0.01) and total household income (P = 0.0001), after control for confounding. The relative risk estimate for those with monthly incomes of <1500 baht (about $60 U.S.) was 3.9 (95% confidence interval 2.1-7.3) compared to those with monthly incomes of at least 5000 baht (about $200). The pattern of increasing risk with decreasing income was observed in all three regions, with significant trends in Bangkok (P = 0.004) and Khonkaen (P = 0.003). This finding may partly explain the high incidence of aplastic anaemia in Thailand. Low socioeconomic status may be a surrogate for one or more environmental factors that could cause aplastic anaemia, such as infectious pathogens or toxic exposures. C1 BOSTON UNIV,SCH MED,SLONE EPIDEMIOL UNIT,BOSTON,MA 02118. KHON KAEN UNIV,FAC MED,DEPT MED,KHON KAEN 40002,THAILAND. PRINCE SONGKLA UNIV,FAC MED,DEPT MED,SONGKHLA,THAILAND. MAHIDOL UNIV,ASIAN INST HLTH DEV,BANGKOK 10700,THAILAND. UNIV S FLORIDA,COLL PUBL HLTH,DEPT EPIDEMIOL & BIOSTAT,TAMPA,FL. NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. RP ISSARAGRISIL, S (reprint author), SIRIRAJ HOSP,FAC MED,DEPT MED,DIV HAEMATOL,BANGKOK 10700,THAILAND. OI Issaragrisil, Surapol/0000-0002-8924-0646 FU NHLBI NIH HHS [HL35068] NR 12 TC 22 Z9 23 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD SEP PY 1995 VL 91 IS 1 BP 80 EP 84 DI 10.1111/j.1365-2141.1995.tb05248.x PG 5 WC Hematology SC Hematology GA RW364 UT WOS:A1995RW36400013 PM 7577657 ER PT J AU MACIEJEWSKI, JP SELLERI, C SATO, T ANDERSON, S YOUNG, NS AF MACIEJEWSKI, JP SELLERI, C SATO, T ANDERSON, S YOUNG, NS TI INCREASED EXPRESSION OF FAS ANTIGEN ON BONE-MARROW CD34(+) CELLS OF PATIENTS WITH APLASTIC-ANEMIA SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE FAS ANTIGEN; BONE MARROW; PROGENITORS; APLASTIC ANEMIA; CD34(+) CELLS ID SURFACE-ANTIGEN; MOLECULAR-CLONING; COLONY FORMATION; ANEMIA; HEMATOPOIESIS; LYMPHOCYTES; APOPTOSIS; INTERFERON; SUPPRESSOR; HEPATITIS AB Fas antigen, a receptor molecule that mediates signals for programmed cell death, is involved in T-cell-mediated killing of malignant, virus-infected or allogeneic target cells, Interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha), potent inhibitors of haemopoiesis, enhance Fas receptor expression on bone marrow (BM) CD34(+) cells, and both cytokines render haemopoietic progenitor cells susceptible to Fas-mediated inhibition of colony formation due to the induction of apoptosis, Haemopoietic suppression in aplastic anaemia (AA) has been associated with aberrant IFN-gamma, increased TNF-beta expression, and elevated numbers of activated cytotoxic T-cells in marrow, We have now examined Fas antigen expression in fresh AA BM samples, In normal individuals few CD34(+) cells expressed Fas antigen and normal marrow cells had low sensitivity to Pas-mediated inhibition of colony formation. In contrast, in early AA, BM CD34(+) cells showed markedly increased percentages of Pas receptor-expressing CD34(+) cells, which correlated with increased sensitivity of AA marrow cells to anti-Fas antibody-mediated inhibition of colony formation. The proportion of Fas antigen-bearing cells was lower in recovered patients' BM. Fas antigen was also detected in the marrow of some patients with myelodysplasia, especially the hypocellular variant, These results are consistent with the hypothesis that AA CD34(+) cells, probably including haemopoietic progenitor cells, express high levels of Fas receptor due to in vivo exposure to IFN-gamma and/or TNF-alpha and are suitable targets for T-cell-mediated killing. Our results suggest that the Pas receptor/Fas ligand system are involved in the pathophysiology of BM failure. RP MACIEJEWSKI, JP (reprint author), NHLBI,HEMATOL BRANCH,BLDG 10,ROOM 7C108,BETHESDA,MD 20892, USA. NR 54 TC 192 Z9 202 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD SEP PY 1995 VL 91 IS 1 BP 245 EP 252 DI 10.1111/j.1365-2141.1995.tb05277.x PG 8 WC Hematology SC Hematology GA RW364 UT WOS:A1995RW36400042 PM 7577642 ER PT J AU SPIELER, RE RUSSO, AC WEBER, DN AF SPIELER, RE RUSSO, AC WEBER, DN TI WATERBORNE LEAD AFFECTS CIRCADIAN VARIATIONS OF BRAIN NEUROTRANSMITTERS IN FATHEAD MINNOWS SO BULLETIN OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY LA English DT Article ID LOCOMOTOR-ACTIVITY; EXPOSURE AB Lead is a potent neurotoxin affecting brain levels of a number of vertebrate neurotransmitters. Reports on these effects are, however, not consistent either among or within species. For example, with lead-intoxicated rats there are reports of decreased acetylcholine (ACh) release and decreased ACh brain levels as well as reports of increased levels or no change in levels. Also, with rats there are reports of increased levels, decreased levels, or no change in brain catecholamines, with lead producing similar changes in both norephinephrine (NE) and dopamine (DA) in some cases and differences in response between the two in others. Although most early reports dealt with whole brain levels, reports on neurotransmitter levels in specific brain regions can be equally conflicting (for references see: Shih and Hanin 1978, Winder 1982, Shellenberger 1984). Similar sorts of discrepancies exist among studies with fishes (Katti and Sathyanesan 1986, Weber et al. 1991). Much of the variation among studies on lead effects on neurotransmitters is, no doubt, due to differences among the studies in variables such as: species, age, dosage and duration, route of administration. However, lead can apparently affect circadian locomotor rhythms of both rats and fishes (Collins et al. 1984, Shafig-ur-Rehman et al. 1986, Weber et al. 1991). Therefore, another possible cause for the variation among studies is that there is an interaction among dosage, sampling time and endogenous rhythms. A lead-produced phase shift or disruption in endogenous neurotransmitter rhythms could in turn elicit a host of varying results and interpretations depending on the circadian time of sampling (Spieler 1992). We elected to examine this possibility in the fathead minnow, Pimephales promelas, a freshwater species widely used for toxicity studies. C1 CALIF STATE UNIV LONG BEACH,DEPT PHYS THERAPY,LONG BEACH,CA 90840. UNIV WISCONSIN,NIEHS,MARINE & FRESHWATER BIOMED RES CTR,MILWAUKEE,WI 53201. RP SPIELER, RE (reprint author), NOVA SE UNIV,CTR OCEANOG,DANIA,FL 33004, USA. FU NIEHS NIH HHS [ES-04184] NR 15 TC 15 Z9 15 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0007-4861 J9 B ENVIRON CONTAM TOX JI Bull. Environ. Contam. Toxicol. PD SEP PY 1995 VL 55 IS 3 BP 412 EP 418 PG 7 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA RH075 UT WOS:A1995RH07500013 PM 8520148 ER PT J AU Carcillo, JA Hough, CJ AF Carcillo, JA Hough, CJ TI Norepinephrine induces expression of c-fos mRNA through the alpha-adrenoceptor in rat aortic rings SO CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY LA English DT Note DE vascular smooth muscle contraction; rat aorta; norepinephrine; c-fos mRNA expression; adrenergic receptor; catecholamine ID SMOOTH-MUSCLE CELLS; ANGIOTENSIN-II; PROTOONCOGENE EXPRESSION; GENE-EXPRESSION; MESSENGER-RNA; ACTIVATION; INDUCTION; MOBILIZATION; STIMULATION; HEART AB We examined whether norepinephrine at pharmacologically relevant doses induces increased expression of c-fos mRNA in rat aortic rings. c-fos mRNA was expressed at norepinephrine concentrations known to cause minimum and maximum contraction of rat aorta in vitro. At the concentration known to cause maximum contraction, norepinephrine produced a marked and sustained increase of c-fos mRNA expression. Induction of c-fos was blocked completely by the alpha(1)-adrenergic antagonist prazosin, partially by the alpha(2)-adrenergic antagonist yohimbine, and not at all by the beta-adrenergic antagonist propranolol. A prazosin inhibition curve showed that 1 nmol/L prazosin inhibited 10 mu mol/L norepinephrine induced c-fos expression by 40%. At the pharmacologic dose known to cause maximum contraction, norepinephrine induces c-fos mRNA expression through the alpha-adrenoceptor in rat aortic rings. C1 UNIV PITTSBURGH,CHILDRENS HOSP PITTSBURGH,DEPT ANESTHESIOL & CRIT CARE MED,PITTSBURGH,PA 15213. BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NIMH,BETHESDA,MD 20892. NR 17 TC 2 Z9 2 U1 0 U2 1 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0008-4212 J9 CAN J PHYSIOL PHARM JI Can. J. Physiol. Pharmacol. PD SEP PY 1995 VL 73 IS 9 BP 1281 EP 1285 PG 5 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA TK791 UT WOS:A1995TK79100008 PM 8748977 ER PT J AU Webster, MJ Ungerleider, LG Bachevalier, J AF Webster, MJ Ungerleider, LG Bachevalier, J TI Development and plasticity of the neural circuitry underlying visual recognition memory SO CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT Symposium of the Centre-de-Recherche-en-Sciences-Neurologiques of the Universite-de-Montreal on Development and Plasticity of the Visual System CY MAY 09-10, 1994 CL MONTREAL, CANADA SP Univ Montreal, Ctr Rech Sci Neurol DE limbic structures; association cortex; amygdala; transient connections; compensatory potential ID INFANT MONKEYS; OBJECT DISCRIMINATION; HIPPOCAMPAL-FORMATION; IMPAIRMENT; LESIONS; SYSTEM; DAMAGE; BRAIN; TASKS; TE AB In adult monkeys, visual recognition memory, as measured by the delayed nonmatching to sample (DNMS) task, requires the interaction between inferior temporal cortical area TE and medial temporal lobe structures (mainly the entorhinal and perirhinal cortical areas). Ontogenetically, monkeys do not perform at adult levels of proficiency on the DNMS task until 2 years of age. Recent studies have demonstrated that this protracted development of visual recognition memory is due to an immaturity of the association areas of the neocortex rather than the medial temporal lobe. For example, lesions of the medial temporal lobe structures in infancy or in adulthood yield profound and permanent visual recognition loss, indicating that the medial temporal lobe structures operate early in life to sustain visual memory. In contrast, early lesions of area TE, unlike late lesions, result in a significant and long-lasting sparing of visual memory ability. Further evidence for neocortical immaturity is provided by studies of the development of opiatergic and cholinergic receptors, of the maturation of metabolic activity, and of the connectivity between inferior temporal areas TE and TEO and cortical and subcortical structures. Together these results indicate greater compensatory potential after neonatal cortical than after neonatal medial temporal removals. In support of this view, early damage to area TE leads to the maintenance of normally transient projections as well as to reorganization in cortical areas outside the temporal lobe. In addition, lesion studies indicate that, during infancy, visual recognition functions are widely distributed throughout many visual association areas but, with maturation, these functions become localized to area TE. Thus, the maintenance of exuberant projections together with reorganization in other cortical areas of the brain could account for the preservation of visual memories in monkeys that have had area TE removed in infancy. RP Webster, MJ (reprint author), NIMH, NEUROPSYCHOL LAB, BLDG 49, ROOM 1B80, BETHESDA, MD 20892 USA. NR 37 TC 22 Z9 22 U1 0 U2 1 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0008-4212 J9 CAN J PHYSIOL PHARM JI Can. J. Physiol. Pharmacol. PD SEP PY 1995 VL 73 IS 9 BP 1364 EP 1371 PG 8 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA TK791 UT WOS:A1995TK79100019 PM 8748986 ER PT J AU ROSENTHAL, AK MCLAUGHLIN, JK GRIDLEY, G NYREN, O AF ROSENTHAL, AK MCLAUGHLIN, JK GRIDLEY, G NYREN, O TI INCIDENCE OF CANCER AMONG PATIENTS WITH SYSTEMIC-SCLEROSIS SO CANCER LA English DT Article DE NEOPLASM; SCLERODERMA; LUNG CANCER; SKIN CANCER; SYSTEMIC SCLEROSIS ID SCLERODERMA; MALIGNANCY; CARCINOMA AB Background. To determine cancer risk among patients with systemic sclerosis and localized scleroderma, a population-based retrospective cohort study was performed. Patients in Sweden with a discharge diagnosis of systemic sclerosis or localized scleroderma were obtained from the computerized database of hospital discharge diagnoses for the years 1965-1983. Nine hundred seventeen patients with systemic sclerosis and 102 with localized scleroderma were identified. Methods. Using record linkage analysis with data from the Swedish National Cancer Registry, standardized incidence ratios (SIR)s (the ratio of observed to expected incidence) were calculated for specific cancer sites. Results. The SIR for developing cancer in the cohort with systemic sclerosis was 1.5 (95% CI, 1.2-1.9). For specific cancer sites, risks were elevated for lung cancer (SIR, 4.9; 95% CI, 2.8-8.1), nonmelanoma skin cancers (SIR, 4.2; 95% CI, 1.4-9.8),and primary liver cancer (SIR, 3.3; 95% CI, 1.1-7.6), There was a suggestive increase in hematopoietic cancers (SIR, 2.3; 95% CI, 0.9-4.8). In contrast, cancer risks in the similarly ascertained cohort with localized scleroderma were no different from those of the general population. Conclusions. This study confirms earlier reports of an association between systemic sclerosis and an increased risk of cancer. Specific tumor sites correspond to the sites commonly affected by fibrosis such as the lung and skin. C1 MED COLL WISCONSIN,DEPT MED,DIV RHEUMATOL,MILWAUKEE,WI 53226. VET AFFAIRS HOSP,MILWAUKEE,WI. NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. UNIV UPPSALA HOSP,CANC EPIDEMIOL UNIT,S-75185 UPPSALA,SWEDEN. NR 23 TC 114 Z9 118 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 1995 VL 76 IS 5 BP 910 EP 914 DI 10.1002/1097-0142(19950901)76:5<910::AID-CNCR2820760528>3.0.CO;2-T PG 5 WC Oncology SC Oncology GA RP851 UT WOS:A1995RP85100027 PM 8625197 ER PT J AU AKIYAMA, SK OLDEN, K YAMADA, KM AF AKIYAMA, SK OLDEN, K YAMADA, KM TI FIBRONECTIN AND INTEGRINS IN INVASION AND METASTASIS SO CANCER AND METASTASIS REVIEWS LA English DT Review DE FIBRONECTIN; INTEGRINS; CELL ADHESION; METASTASIS; INVASION ID CELL-BINDING DOMAIN; ARG-GLY-ASP; SITE-DIRECTED MUTAGENESIS; HUMAN-PLASMA FIBRONECTIN; III CONNECTING SEGMENT; FIBRO-SARCOMA CELLS; SYNTHETIC PEPTIDES; EXTRACELLULAR-MATRIX; TYROSINE PHOSPHORYLATION; ADHESION MOLECULES AB The adhesive glycoprotein fibronectin and integrin receptors appear to play important roles in the progression of metastatic disease. Fibronectin is a multifunctional extracellular glycoprotein that has at least two independent cell adhesion regions with different receptor specificities. The cell adhesive region in the central portion of fibronectin is comprised of at least two minimal amino acid sequences - an Arg-Gly-Asp (RGD) sequence and a Pro-His-Ser-Arg-Asn (PHSRN) sequence - which function in synergy. Another cell adhesive region is located near the carboxy-terminus in the alternatively spliced IIICS module. The critical minimal sequences for this region are Leu-Asp-Val (LDV) and Arg-Glu-Asp-Val (REDV) which function in an additive rather than synergistic fashion. Integrins are heterodimeric, transmembrane cell adhesion receptors for fibronectin and other extracellular matrix molecules. Several different integrins bind to fibronectin. The alpha(5) beta(1) fibronectin-specific integrin binds to the central RGD/PHSRN site. The alpha(4) beta(1) integrin binds to the IIICS site. Fibronectin-integrin interactions are important in tumor cell migration, invasion, and metastasis. In addition to promoting cell adhesion to the extracellular matrix, these proteins may also function in chemotaxis and control of proliferation. Peptide and antibody inhibitors of fibronectin and integrin functions have been shown to be effective inhibitors of metastasis, and are potentially important reagents for the study and control of cancer. C1 NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. RP AKIYAMA, SK (reprint author), NIDR,DIR,DEV BIOL LAB,BLDG 30,ROOM 421,BETHESDA,MD 20892, USA. NR 117 TC 230 Z9 233 U1 2 U2 20 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-7659 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD SEP PY 1995 VL 14 IS 3 BP 173 EP 189 DI 10.1007/BF00690290 PG 17 WC Oncology SC Oncology GA TB054 UT WOS:A1995TB05400002 PM 8548867 ER PT J AU MUIRHEAD, CR AF MUIRHEAD, CR TI CHILDHOOD LEUKEMIA IN METROPOLITAN REGIONS IN THE UNITED-STATES - A POSSIBLE RELATION TO POPULATION-DENSITY SO CANCER CAUSES & CONTROL LA English DT Article DE CHILDHOOD LEUKEMIA; CENSUS; POPULATION DENSITY; SOCIODEMOGRAPHIC VARIABLES; UNITED STATES ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CHILDREN; CANCER; EPIDEMIOLOGY; RISK AB Following recent research in Great Britain, the geographic incidence of leukemia and non-Hodgkin's lymphoma among White children in three metropolitan regions of the United States (San Francisco-Oakland, CA; Detroit, MI; and Atlanta, GA) during 1978-82 has been analyzed using census tract-specific data. There was no evidence of a general tendency for cases to cluster geographically, in contrast to results from Britain. Further, rates did not vary with median income or education levels for census tracts. However, there was a statistically significant increasing trend in incidence rates with increasing population density: relative risk for highest relative to fewest category = 1.4 (95% percent confidence interval [CI] = 1.1-2.0) for White population density, and 1.4 (CI = 1.0-2.0) for total population density. The interpretation of these findings is unclear and further investigation is required It is possible that population density is acting as a surrogate for some virus-related factor. C1 NCI,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20892. RP MUIRHEAD, CR (reprint author), NATL RADIOL PROTECT BOARD,DIDCOT OX11 0RQ,OXON,ENGLAND. NR 26 TC 31 Z9 31 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD SEP PY 1995 VL 6 IS 5 BP 383 EP 388 DI 10.1007/BF00052177 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA RU542 UT WOS:A1995RU54200001 PM 8547535 ER PT J AU HILDESHEIM, A CHEN, CJ CAPORASO, NE CHENG, YJ HOOVER, RN HSU, MM LEVINE, PH CHEN, IH CHEN, JY YANG, CS DALY, AK IDLE, JR AF HILDESHEIM, A CHEN, CJ CAPORASO, NE CHENG, YJ HOOVER, RN HSU, MM LEVINE, PH CHEN, IH CHEN, JY YANG, CS DALY, AK IDLE, JR TI CYTOCHROME P4502E1 GENETIC POLYMORPHISMS AND RISK OF NASOPHARYNGEAL CARCINOMA - RESULTS FROM A CASE-CONTROL STUDY CONDUCTED IN TAIWAN SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID VOLATILE NITROSAMINE LEVELS; RESPIRATORY NASAL-MUCOSA; CIGARETTE-SMOKING; LUNG-CANCER; SALTED FISH; METABOLISM; AREAS; CHINA; MICROSOMES; INDUCTION AB CYP2E1 is responsible for the metabolic activation of nitrosamines believed to be involved in the pathogenesis of various tumors, Nasopharyngeal carcinoma (NPC) is a tumor thought to be linked to nitrosamine exposure, To investigate the possible role of CYP2E1 genetic polymorphisms in the etiology of this tumor, we investigated 50 histologically confirmed NPC cases from Taiwan and 50 controls matched to cases on age, sex, and residence. Samples were examined for RFLPs in the CYP2E1 gene by PCR amplification followed by digestion with DraI and RsaI, Among healthy controls, the allelic frequency of wild-type and variant forms of CYP2E1 were 79 and 21%, respectively, using DraI enzyme digestion and 82 and 18%, respectively, using RsaI enzyme digestion, As compared with individuals who were homozygous for the mild-type CYP2E1 gene, those found to be homozygous for the variant form of the gene by DraI digestion were at a 5-fold excess risk of disease (95% confidence interval = 0.95-16), Similarly, subjects homozygous for the variant form of the CYP2E1 gene by RsaI digestion were at 7.7-fold excess risk of developing NPC (95% confidence interval = 0.87-68), Individuals found to be heterozygous for the gene were at similar risk of disease compared to those homozygous for the wild-type gene, A strong association was observed between the RFLPs detected by DraI and RsaI digestion of CYP2E1; a correlation coefficient of 0.86 for controls and 0.91 for cases was observed. Interestingly, all individuals with the variant form of CYPZE1 detected by RsaI enzyme digestion also exhibited the variant form of the gene using DraI enzyme digestion, although the reverse was not always true, Our results confirm previous findings suggesting that the distribution of CYP genotypes among Oriental populations varies from that observed among Caucasians and demonstrate for the first time a possible association between CYP2E1 genetic polymorphisms and the risk of developing NPC. C1 NCI,GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892. NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. NATL TAIWAN UNIV,COLL PUBL HLTH,INST EPIDEMIOL,TAIPEI,TAIWAN. NATL TAIWAN UNIV HOSP,DEPT OTOLARYNGOL,TAIPEI,TAIWAN. MACKAY HOSP,DEPT OTOLARYNGOL,TAIPEI,TAIWAN. NATL TAIWAN UNIV,COLL MED,INST MICROBIOL,TAIPEI,TAIWAN. GENOTYPE LTD,NEWCASTLE TYNE,TYNE & WEAR,ENGLAND. RP HILDESHEIM, A (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N ROOM 443,BETHESDA,MD 20892, USA. RI Chen, Chien-Jen/C-6976-2008; Daly, Ann/H-3144-2011; Chen, Jen-Yang/D-2085-2010; OI Daly, Ann/0000-0002-7321-0629; Idle, Jeff/0000-0002-6143-1520 NR 34 TC 68 Z9 74 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 1995 VL 4 IS 6 BP 607 EP 610 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA RU350 UT WOS:A1995RU35000006 PM 8547826 ER PT J AU NICOLET, CM BURKHOLDER, JK GAN, J CULP, J KASHMIRI, SVS SCHLOM, J YANG, NS SONDEL, PM AF NICOLET, CM BURKHOLDER, JK GAN, J CULP, J KASHMIRI, SVS SCHLOM, J YANG, NS SONDEL, PM TI EXPRESSION OF A TUMOR-REACTIVE ANTIBODY-INTERLEUKIN-2 FUSION PROTEIN AFTER IN-VIVO PARTICLE-MEDIATED GENE DELIVERY SO CANCER GENE THERAPY LA English DT Article DE PARTICLE-MEDIATED GENE TRANSFER; ANTIBODY-IL-2 FUSION PROTEIN; IMMUNOTHERAPY; TUMOR-ASSOCIATED ANTIGEN ID RECOMBINANT INTERLEUKIN-2; HUMAN-LYMPHOCYTES; CELLS; INVIVO; BOMBARDMENT; ANTIGEN; THERAPY; B72.3; DNA AB We have used a particle-mediated gene transfer method to analyze the posttransfection expression pattern of an antibody-cytokine fusion protein (FP) in vivo. The FP, denoted CC49-IL2, consists of a single-chain antibody containing the antigen recognition domain from the murine monoclonal antibody CC49 (recognizing the rumor-associated antigen TAG-72), a human IgG1 constant heavy chain, and human interleukin-2 (IL-2). This FP can bind to TAC-72-expressing tumor cells and exhibits IL-2 activity. To induce systemic levels of this FP in vivo, we have transferred the FP gene into murine epidermal cells by direct delivery of DNA-coated gold particles using a transcutaneous ''gene gun.'' After the pericutaneous delivery of the FP gene via gold particles, production of the exogenous FP was detected al the epidermal target site. The FP produced in vivo at the site of gene delivery has cytokine activity and antigen recognition capabilities similar to those present in CC49-IL2 FP purified from hybridoma culture supernatants in vitro. FP was also detectable in the serum from test animals treated with particle-mediated gene transfer. Time course experiments indicated that serum levels of FP reached a peak level within 8 hours after DNA delivery, whereas the epidermal target tissue levels continued to increase for 24 hours before plateauing. Our results indicate that exogenous protein levels consistent with immunotherapeutic effects of the FP can be readily achieved at the skin tissue site of gene delivery, with the potential for achieving therapeutic levels systemically. C1 UNIV WISCONSIN,CTR COMPREHENS CANC,MADISON,WI 53792. AGRACETUS INC,MIDDLETON,WI. NCI,TUMOR IMMUNOL LAB,BETHESDA,MD 20892. UNIV WISCONSIN,SCH MED,DEPT PATHOL,MADISON,WI 53706. NR 34 TC 21 Z9 21 U1 1 U2 1 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD SEP PY 1995 VL 2 IS 3 BP 161 EP 170 PG 10 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA RT282 UT WOS:A1995RT28200001 PM 8528959 ER PT J AU THOMPSON, FH EMERSON, J OLSON, S WEINSTEIN, R LEAVITT, SA LEONG, SPL EMERSON, S TRENT, JM NELSON, MA SALMON, SE TAETLE, R AF THOMPSON, FH EMERSON, J OLSON, S WEINSTEIN, R LEAVITT, SA LEONG, SPL EMERSON, S TRENT, JM NELSON, MA SALMON, SE TAETLE, R TI CYTOGENETICS OF 158 PATIENTS WITH REGIONAL OR DISSEMINATED MELANOMA - SUBSET ANALYSIS OF NEAR-DIPLOID AND SIMPLE KARYOTYPES SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID MALIGNANT-MELANOMA; CELLULAR ONCOGENES; FAMILIAL MELANOMA; CANCER-CELLS; CHROMOSOME; AMPLIFICATION; DELETION; TUMORS; LIPOSARCOMA; T(12-16) AB We report on the cytogenetic analyses of 158 cases of metastatic malignant melanoma, comprised of 63 cases with regional disease (RD) and 95 cases with distant (metastatic) disease (DD). Clonal structural abnormalities were identified in 126 (80%) cases and were significantly increased (< 0.01 after adjusting for multiple comparisons) on chromosomes fin order of frequency of involvement) 1, 6, 7, 11, 9, and 3. Clustering of breakpoints occurred at 1p36, 1p22-q21, 6p11-q21, 9p, 11q23-qter, 13p (especially for cases with DD), and 19q13. The most common clonal numerical abnormalities, in a subset of 49 near-diploid cases were -10, -22, -9, +7, -19, and -Y. Analysis of chromosome segment gains and losses (CSRP) showed frequent loss of chromosomes 6 and 10, followed by equal rates of involvement of chromosomes 1, 7, and 9. Whole or segmental losses of chromosome 9 (especially 9p) correlate well with recent molecular genetic studies identifying putative suppressor genes, and are also likely important genetic abnormalities. However, based on the frequency of abnormalities in this large series of metastatic melanomas, it is likely that structural abnormalities of 1 and 6, and -10 are important in the pathogenesis of sporadic advanced melanoma. C1 UNIV ARIZONA,ARIZONA CANC CTR,TUCSON,AZ 85724. UNIV ARIZONA,DEPT MED,TUCSON,AZ. UNIV ARIZONA,DEPT PATHOL,TUCSON,AZ. UNIV CALIF SAN FRANCISCO,MT ZION MED CTR,DEPT SURG,SAN FRANCISCO,CA 94120. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. FU NCI NIH HHS [CA41183] NR 61 TC 124 Z9 130 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD SEP PY 1995 VL 83 IS 2 BP 93 EP 104 DI 10.1016/0165-4608(95)00057-V PG 12 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA RY479 UT WOS:A1995RY47900001 PM 7553595 ER PT J AU DADMARZ, R SGAGIAS, MK ROSENBERG, SA SCHWARTZENTRUBER, DJ AF DADMARZ, R SGAGIAS, MK ROSENBERG, SA SCHWARTZENTRUBER, DJ TI CD4+ T-LYMPHOCYTES INFILTRATING HUMAN BREAST-CANCER RECOGNIZE AUTOLOGOUS TUMOR IN AN MHC-CLASS-II RESTRICTED FASHION (VOL 40, PG 1, 1995) SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Correction, Addition RP DADMARZ, R (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B04,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD SEP PY 1995 VL 41 IS 3 BP 201 EP 201 DI 10.1007/BF01521348 PG 1 WC Oncology; Immunology SC Oncology; Immunology GA RY345 UT WOS:A1995RY34500011 ER PT J AU HAWN, MT UMAR, A CARETHERS, JM MARRA, G KUNKEL, TA BOLAND, CR KOI, M AF HAWN, MT UMAR, A CARETHERS, JM MARRA, G KUNKEL, TA BOLAND, CR KOI, M TI EVIDENCE FOR A CONNECTION BETWEEN THE MISMATCH REPAIR SYSTEM AND THE G(2) CELL-CYCLE CHECKPOINT SO CANCER RESEARCH LA English DT Note ID 6-THIOGUANINE; CANCER; DNA; MECHANISM; RESISTANT; TOLERANCE; COLON; LINE AB The human colon tumor cell line HCT116 is deficient in wild-type hMLH1, is defective in mismatch repair (MMR), exhibits microsatellite instability, and is tolerant to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Transferring a normal copy of hMLH1 on chromosome 3 into the cell line restores MMR activity, stabilizes microsatellite loci, and increases the sensitivity of the cell to MNNG. Previous studies in other cell lines tolerant to alkylating agents such as MNNG or N-methylnitrosourea have shown cross-tolerance to 6-thioguanine (6TG), leading to a hypothesis that tolerance to MNNG or 6TG may be the result of MMR deficiency. To test this hypothesis, we studied the effects of 6TG on the MNNG-tolerant, MMR-deficient HCT116 cell line and its MNNG-sensitive, MMR-proficient, MNNG-tolerant, and MMR-deficient derivatives. Continuous exposure to low doses of 6TG (0.31-1.25 mu g/ml) had no apparent effect on colony-forming ability (CFA) in MNNG-tolerant, MMR-deficient cells, whereas MNNG-sensitive, MMR-proficient cells exhibited a dose-dependent decrease in CFA. Growth kinetics and cell cycle analysis revealed that the growth of 6TG-treated HCT116+chr3 cells was arrested at G(2) after exposure to low dose of 6TG. In contrast, the same exposure to 6TG did not induce G(2) arrest but rather a G(1) delay in HCT116 and HCT116+chr2. To obtain further evidence for the role of MMR on 6TG and MNNG toxicity, we isolated an MNNG-resistant revertant clone, M2, from the MNNG-sensitive, MMR-proficient HCT116+chr3 cell line and characterized the MMR activity, hMLH1 status, and 6TG response. The results showed that M2 cells lost MMR activity as well as the previously introduced normal hMLH1 gene. Restoration of the CFA of M2 and an absence of G(2) arrest were observed after treatment with low doses of 6TG. These results suggest that the mismatch repair system interacts with the G(2) checkpoint in response to 6TG or MNNG-induced DNA lesions. The results further suggest that any agent that induces DNA mispairs will cause G(2) arrest in MMR-proficient cells but not in MMR deficient cells. C1 UNIV MICHIGAN,MED CTR,DEPT INTERNAL MED,DIV GASTROENTEROL,ANN ARBOR,MI 48109. VET AFFAIRS MED CTR,GASTROENTEROL SECT,ANN ARBOR,MI 48105. NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. RI Koi, Minoru/C-3489-2012; Koi, Minoru/G-9197-2014 FU NCI NIH HHS [CA39233, CA46592, R25 CA57716]; NIDDK NIH HHS [K08 DK002433, K08 DK002433-05] NR 26 TC 324 Z9 329 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 1995 VL 55 IS 17 BP 3721 EP 3725 PG 5 WC Oncology SC Oncology GA RR739 UT WOS:A1995RR73900009 PM 7641183 ER PT J AU SANO, H KAWAHITO, Y WILDER, RL HASHIRAMOTO, A MUKAI, S ASAI, K KIMURA, S KATO, H KONDO, M HLA, T AF SANO, H KAWAHITO, Y WILDER, RL HASHIRAMOTO, A MUKAI, S ASAI, K KIMURA, S KATO, H KONDO, M HLA, T TI EXPRESSION OF CYCLOOXYGENASE-1 AND CYCLOOXYGENASE-2 IN HUMAN COLORECTAL-CANCER SO CANCER RESEARCH LA English DT Article ID PROSTAGLANDIN ENDOPEROXIDE SYNTHASE; FIBROBLAST GROWTH-FACTOR; RAT COLONIC EPITHELIUM; CELL-WALL ARTHRITIS; LARGE-BOWEL; PROLIFERATIVE ACTIVITY; RHEUMATOID-ARTHRITIS; SYNOVIAL TISSUES; TUMOR PROMOTION; REDUCED RISK AB Several studies indicate that nonsteroidal anti-inflammatory drugs including indomethacin, aspirin, sulindac, and piroxicam reduce the risk of colon cancer. Furthermore, nonsteroidal anti-inflammatory drugs that inhibit the cyclooxygenase (COX) enzyme were shown to inhibit the development of colon cancer in animal models of carcinogenesis. Nonsteroidal anti-inflammatory drugs inhibit the enzymatic activity of both the constitutive (COX-1) and inducible (COX-2) isoforms of COX enzyme. We have investigated the expression of COX-1 and COX-2 polypeptides in human colon cancer tissues using immunohistochemistry. Enhanced COX-2 expression was observed in colon cancer tissues from 15 subjects with clinically diagnosed colorectal cancer. Marked COX-2 expression was observed in cancer cells, inflammatory cells, vascular endothelium, and fibroblasts of the lesional tissues compared with the nonlesional and normal colon tissues. The extent and intensity of the immunoreactive COX-2 in cancer cells was much greater than that of the other cell types, In contrast, the expression of COX-1 polypeptide was weak in both normal and cancerous specimens. These data suggest that the enhanced expression of the COX-2 gene in colon cancer tissues may contribute to the enhanced synthesis of prostaglandin E(2) by the colon cancer tissues. Enhanced expression of COX-2 may play a role in the pathogenesis of colon cancer. Furthermore, selective inhibition of COX-2 may prove to be more efficacious in the retardation of colon cancer development. C1 NIAMSD,ARTHRITIS & RHEUMATISM BRANCH,BETHESDA,MD 20892. AMER RED CROSS,JEROME H HOLLAND LAB,DEPT MOLEC BIOL,ROCKVILLE,MD 20855. RP SANO, H (reprint author), KYOTO PREFECTURAL UNIV MED,DEPT INTERNAL MED 1,KAMIGYO KU,465 KAJII CHO,KYOTO 602,JAPAN. RI Hla, Timothy/G-5873-2012 OI Hla, Timothy/0000-0001-8355-4065 FU NHLBI NIH HHS [HL 49094]; NIDDK NIH HHS [DK 45659] NR 53 TC 991 Z9 1043 U1 2 U2 18 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 1995 VL 55 IS 17 BP 3785 EP 3789 PG 5 WC Oncology SC Oncology GA RR739 UT WOS:A1995RR73900023 PM 7641194 ER PT J AU MOSCOW, JA GONG, MK HE, R SGAGIAS, MK DIXON, KH ANZICK, SL MELTZER, PS COWAN, KH AF MOSCOW, JA GONG, MK HE, R SGAGIAS, MK DIXON, KH ANZICK, SL MELTZER, PS COWAN, KH TI ISOLATION OF A GENE ENCODING A HUMAN REDUCED FOLATE CARRIER (RFC1) AND ANALYSIS OF ITS EXPRESSION IN TRANSPORT-DEFICIENT, METHOTREXATE-RESISTANT HUMAN BREAST-CANCER CELLS SO CANCER RESEARCH LA English DT Article ID BINDING-PROTEIN; MEMBRANE-TRANSPORT; LEUKEMIA-CELLS; L1210 CELLS; KB CELLS; CDNA; LINE; PLACENTA; SEQUENCE; CLONING AB Our laboratory has previously reported the isolation of a murine cDNA which restores reduced folate carrier (RFC) activity and methotrexate (MTX) sensitivity to a MTX-resistant, transport-deficient human breast cancer cell line (MTX(R) ZR-75-1) (K, H, Dixon et al,, J, Biol, Chem,, 269: 17-20, 1994), Using this murine cDNA as a probe, we have isolated two homologous overlapping partial cDNAs from a human testis cDNA library, In addition, using human cDNA as a probe, we have isolated a 20-kb human genomic fragment which contains RFC coding regions, Analysis of the nucleotide sequence of these clones revealed that the human RFC gene, RFC1, is approximately 65% homologous to the murine and hamster genes, Using a human genomic Pr plasmid clone containing RFC1, we mapped the location of RFC1 by fluorescence in situ hybridization to the end of the long arm of chromosome 21 (21q22.2-q22.3). Fluorescence in situ hybridization analysis also showed that two copies of RFC1 were present in MTX(R) ZR-75-1 cells, and showed no evidence of rearrangement of this gene, Northern blot analysis of MTX(R) ZR-75-1 cells demonstrated a marked decrease in the level of the 3-kb RFC1 transcript relative to the parental cell line, and Western blot analysis using a polyclonal antibody raised against a peptide generated from the RFC1 sequence showed decreased expression of an approximately M(r) 56,000 protein in MTX(R) ZR-75-1 cells. Finally, MTX(R) ZR-75-1 cells transfected with an RFC1 gene showed increased MTX uptake, which was more sensitive to competition by folinic acid than by folic acid, Therefore, decreased RFC1 expression appears to be the molecular mechanism of decreased MTX uptake in this MTX-resistant cell line. C1 NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892. RP MOSCOW, JA (reprint author), NCI,MED BREAST CANC SECT,MED BRANCH,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 25 TC 180 Z9 184 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 1995 VL 55 IS 17 BP 3790 EP 3794 PG 5 WC Oncology SC Oncology GA RR739 UT WOS:A1995RR73900024 PM 7641195 ER PT J AU FRANCO, JL GHOSH, P WILTROUT, RH CARTER, CRD ZEA, AH MOMOZAKI, N OCHOA, AC LONGO, DL SAYERS, TJ KOMSCHLIES, KL AF FRANCO, JL GHOSH, P WILTROUT, RH CARTER, CRD ZEA, AH MOMOZAKI, N OCHOA, AC LONGO, DL SAYERS, TJ KOMSCHLIES, KL TI PARTIAL DEGRADATION OF T-CELL SIGNAL-TRANSDUCTION MOLECULES BY CONTAMINATING GRANULOCYTES DURING PROTEIN EXTRACTION OF SPLENIC T-CELLS FROM TUMOR-BEARING MICE SO CANCER RESEARCH LA English DT Article ID LYMPHOCYTES-T; BONE-MARROW; EXPRESSION; PROTEASES; INDUCTION; CARCINOMA; ANTIBODY AB Flavone-8-acetic acid plus recombinant human interleukin 2 is a successful antitumor therapy in mice bearing the Renca murine renal cell carcinoma, This report demonstrates that T cells, particularly CD8(+) T cells, are critical for the generation of this response, Initial experiments examining T-cell signal transduction proteins demonstrated that T cells from Renca-bearing mice had undetectable levels of p56(lck) and zeta-chain of the T-cell receptor and that flavone-8-acetic acid and recombinant human interleukin 2 therapy could be used as a model for reversal of these alterations, However, further experimentation showed that the majority of the reduction in zeta-chain and part of the reduction in p56(lck) was due to degradation of these molecules during protein extraction caused by mature granulocytes contaminating the enriched T-cell population, This was not the case for nuclear c-Rel or NF kappa B p65, which remained at undetectable/reduced levels in the absence of granulocytes, confirming our previous data that transcription factor alterations exist in tumor-bearing mice. Thus, most of the reduction in zeta-chain in T cells from Renca-bearing mice is due to granulocyte contamination and emphasizes the need to use pure T-cell populations and/or sufficient amounts and types of protease inhibitors when quantitating proteins in T cells from tumor-bearing mice. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,OFF ASSOCIATE DIRECTOR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,CLIN SERV PROGRAM,FREDERICK,MD 21702. ONCOTHERAPEUT INC,CRANBURY,NJ 08512. RI Sayers, Thomas/G-4859-2015 NR 22 TC 43 Z9 44 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 1995 VL 55 IS 17 BP 3840 EP 3846 PG 7 WC Oncology SC Oncology GA RR739 UT WOS:A1995RR73900031 PM 7641202 ER PT J AU DABHOLKAR, MD REED, E AF DABHOLKAR, MD REED, E TI MALIGNANT AND NONMALIGNANT BRAIN-TISSUES DIFFER IN THEIR MESSENGER-RNA EXPRESSION PATTERNS FOR ERCC1 AND ERCC2 - REPLY SO CANCER RESEARCH LA English DT Letter ID REPAIR C1 NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NR 10 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 1995 VL 55 IS 17 BP 3933 EP 3934 PG 2 WC Oncology SC Oncology GA RR739 UT WOS:A1995RR73900045 ER PT J AU DIWAN, BA RICE, JM AF DIWAN, BA RICE, JM TI EFFECT OF STAGE OF DEVELOPMENT ON FREQUENCY AND PATHOGENESIS OF KIDNEY TUMORS INDUCED IN NOBLE (NB) RATS EXPOSED PRENATALLY OR NEONATALLY TO N-NITROSOETHYLUREA SO CARCINOGENESIS LA English DT Article ID RENAL TUMORS; NEPHRO-BLASTOMA; INDUCTION; DIMETHYLNITROSAMINE; ETHYLNITROSOUREA; RABBITS AB Wilms' tumor of kidney, a common human childhood neoplasm, is modeled by nephroblastomas induced by prenatal exposure of some rodents to alkylating agents. Noble (Nb) rats are especially susceptible. We studied the ontogeny of susceptibility by treatment with N-nitrosoethyl-urea (NEU) on gestation day 10, 12, 14, 16 or 18 or neonatal day 1, 3, 5, 7 or 10. No nephroblastomas were observed in offspring exposed to NEU on day 10 or 12 of gestation. In contrast, nephroblastomas commonly occurred in rats exposed on gestation day 14, 16 or 18 of gestation, with the highest incidence (48%) after treatment on day 18. Nephroblastomas were rare (<10%), but renal mesenchymal tumors were common (25-30%) in rats exposed to NEU on day 1 or 3 after birth. In rats exposed to NEU on day 7 or 10 only renal mesenchymal tumors were seen. Thus our results suggest that the stage of differentiation of fetal and neonatal kidneys at the time of NEU administration determines the frequency and type of kidney tumors induced in Nb rats. Since NEU induces both nephroblastomas and mesenchymal tumors in this strain, this experimental model may prove useful for the study of molecular mechanisms involved in the development of these two histogenetically different types of kidney tumors. C1 NCI, FREDERICK CANC RES & DEV CTR, COMPARAT CARCINOGENESIS LAB, FREDERICK, MD 21702 USA. RP DIWAN, BA (reprint author), SAIC FREDERICK, BIOL CARCINOGENESIS & DEV PROGRAM, FREDERICK, MD 21702 USA. NR 31 TC 9 Z9 9 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1995 VL 16 IS 9 BP 2023 EP 2028 DI 10.1093/carcin/16.9.2023 PG 6 WC Oncology SC Oncology GA RV296 UT WOS:A1995RV29600003 PM 7554049 ER PT J AU FELLEYBOSCO, E MIRKOVITCH, J AMBS, S MACE, K PFEIFER, A KEEFER, LK HARRIS, CC AF FELLEYBOSCO, E MIRKOVITCH, J AMBS, S MACE, K PFEIFER, A KEEFER, LK HARRIS, CC TI NITRIC-OXIDE AND ETHYLNITROSOUREA - RELATIVE MUTAGENICITY IN THE P53 TUMOR-SUPPRESSOR AND HYPOXANTHINE-PHOSPHORIBOSYLTRANSFERASE GENES SO CARCINOGENESIS LA English DT Article ID ETHYL-N-NITROSOUREA; POLYMERASE CHAIN-REACTION; GENOTYPIC ANALYSIS; INDUCED MUTATIONS; HUMAN-CELLS; 5-METHYLCYTOSINE; REPAIR; MUTAGENESIS; FIBROBLASTS; TOXICITY AB Nitric oxide (NO) is a cellular messenger which is mutagenic in bacteria and human TK6 cells and induces deamination of 5-methylcytosine (5meC) residues in vitro. The aims of this study were: (i) to investigate whether NO induces 5meC deamination in codon 248 of the p53 gene in cultured human bronchial epithelial cells (BEAS-2B); and (ii) to compare NO mutagenicity to that of ethylnitrosourea (ENU), a strong mutagen. Two approaches were used: (i) a novel genotypic assay, using RFLP/PCR technology on purified exon VII sequence of the p53 gene; and (ii) a phenotypic (HPRT) mutation assay using 6-thioguanine selection. BEAS-2B cells were either exposed to 4 mM DEA/NO (Et(2)N[N2O2]Na, an agent that spontaneously releases NO into the medium) or transfected with the inducible nitric oxide synthase (iNOS) gene. The genotypic mutation assay, which has a sensitivity of 1 x 10(-6), showed that 4 mM ENU induces detectable numbers of G --> A transitions in codon 248 of p53 while 5-methylcytosine deamination was not detected in either iNOS-transfected cells or cells exposed to 4 mM DEA/NO. Moreover, ENU was dose-responsively mutagenic in the phenotypic HPRT assay, reaching mutation frequencies of 24 and 96 times that of untreated control cells at ENU concentrations of 4 and 8 mM respectively; by contrast, 4 mM DEA/NO induced no detectable mutations in this assay, nor were any observed in cells transfected with murine iNOS. We conclude that if NO is at all promutagenic in these cells, it is significantly less so than the ethylating mutagen, ENU. C1 SWISS INST EXPTL CANC RES,CH-1066 EPALINGES,SWITZERLAND. NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. NESTLE SA,VERS CHEZ LES BLANCS,SWITZERLAND. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RP FELLEYBOSCO, E (reprint author), INST PHARMACOL & TOXICOL,BUGNON 27,CH-1007 LAUSANNE,SWITZERLAND. RI Keefer, Larry/N-3247-2014; Felley-Bosco, Emanuela/E-7484-2017 OI Keefer, Larry/0000-0001-7489-9555; Felley-Bosco, Emanuela/0000-0002-3408-0294 NR 43 TC 32 Z9 33 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1995 VL 16 IS 9 BP 2069 EP 2074 DI 10.1093/carcin/16.9.2069 PG 6 WC Oncology SC Oncology GA RV296 UT WOS:A1995RV29600010 PM 7554056 ER PT J AU TOPOL, LZ BLAIR, DG AF TOPOL, LZ BLAIR, DG TI ACTIVATION OF THE MITOGEN-ACTIVATED PROTEIN-KINASE CASCADE IN RESPONSE TO THE TEMPERATURE INDUCIBLE EXPRESSION OF V-MOS KINASE SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID MURINE SARCOMA-VIRUS; SENSITIVE TRANSFORMATION MUTANT; SIGNAL-REGULATED KINASES; MAP KINASE; XENOPUS-OOCYTES; TYROSINE PHOSPHORYLATION; NUCLEOTIDE-SEQUENCE; MEIOTIC MATURATION; ONCOGENE PRODUCT; CELLS AB We have characterized activation of the MAP kinase cascade in an inducible system in response to the temperature-sensitive (ts) expression of the v-mos oncogene. Transformation of immortalized rat embryo fibroblasts by a ts isolate of Moloney murine sarcoma virus (Mo-MuSVts110) constitutively activates MAP kinases (ERK-1 and ERK-2) and MAP kinase kinases (MKK-1 and MKK-2) only at the permissive temperature when v-mos kinase is present and active. Following a shift of the fs-transformed, serum-starved cells from the nonpermissive to permissive temperature, MAP kinases and both MKK-7 and MKK-2 are activated within 1-2 h, concurrent with the reappearance of active mos kinase. Raf-1 kinase activity increases more slowly in response to the reappearance of v-mos, and the mobility shift indicative of hyperphosphorylation was only detected ts h after the temperature transition. Our data show that MAP kinase cascade activation is an early event following the reappearance of v-mos expression and v-mos kinase activity upon temperature shift, while the first manifestation of morphological transformation appears 24 h after the shift to permissive temperature. These results support the hypothesis that mos acts through the MKK to induce cell transformation. RP TOPOL, LZ (reprint author), NCI, MOLEC ONCOL LAB, POB B, FREDERICK, MD 21702 USA. NR 49 TC 5 Z9 5 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD SEP PY 1995 VL 6 IS 9 BP 1119 EP 1127 PG 9 WC Cell Biology SC Cell Biology GA RU204 UT WOS:A1995RU20400010 PM 8519689 ER PT J AU LI, LW TUCKER, RW HENNINGS, H YUSPA, SH AF LI, LW TUCKER, RW HENNINGS, H YUSPA, SH TI INHIBITORS OF THE INTRACELLULAR CA2+-ATPASE IN CULTURED MOUSE KERATINOCYTES REVEAL COMPONENTS OF TERMINAL DIFFERENTIATION THAT ARE REGULATED BY DISTINCT INTRACELLULAR CA2+ COMPARTMENTS SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID PROTEIN-KINASE-C; EPIDERMAL GROWTH-FACTOR; GENE-EXPRESSION; CALCIUM REGULATION; TUMOR PROMOTER; EPIDERMOLYTIC HYPERKERATOSIS; EXTRACELLULAR CALCIUM; ENDOPLASMIC-RETICULUM; MURINE KERATINOCYTES; CYCLOPIAZONIC ACID AB Differentiation of mammalian epidermis is associated with spatially and temporally coordinated changes in gene expression as cells migrate from the proliferative basal cell compartment through the nonproliferative spinous and granular cell layers where the terminal phase of maturation is completed. Previous studies have suggested that a gradient of Ca2+ in the epidermis in vivo and increased extracellular Ca2+ in vitro induce differentiation of mammalian epidermal keratinocytes. Chelation of intracellular free Ca2+ prevents this Ca2+ induced differentiation, but sites bf action for intracellular Ca2+ remain undefined. in this study, thapsigargin (Tg) and cyclopiazonic acid (CPA), inhibitors of the endoplasmic reticulum Ca2+-ATPase, were used to evaluate the relative: contribution of cytoplasmic and stored Ca2+ to Ca2+-induced terminal differentiation of cultured mouse keratinocytes. A sustained increase of both intracellular free Ca2+ (Ca-i) and ionomycin-sensitive Ca2+ stores is associated with Ca2+-induced keratinocyte terminal differentiation. Tg and CPA was used to change this coordinated regulation of free and stored Ca2+. In the absence of extracellular Ca2+, both Tg and CPA transiently increase Ca-i and deplete intracellular Ca2+ stores; while in the presence of extracellular Ca2+, Tg and CPA stimulate Ca2+ influx and cause a sustained increase in Ca-i while depleting stored Ca2+. In the presence of extracellular Ca2+, Tg (5 to 20 nM) and CPA (5 to 25 mu M) inhibit Ca2+-induced morphological changes and stratification and prevent the suppression of DNA synthesis by Ca2+. Tg and CPA also inhibit the expression of mRNA and protein for specific epidermal spinous cell markers, keratins 1 (K1) and 10 (K10), prevent the redistribution of E-cadherin from a diffuse membranous pattern to concentration at cell-cell junctions, and inhibit the activation of a reporter gene regulated by a K1 enhancer element shown previously to be Ca2+ sensitive. These effects of Tg and CPA can be reversed by increasing the extracellular Ca2+ to levels that partially restore Ca2+ stores. In contrast, Tg and CPA enhance the expression of profilaggrin and loricrin mRNA and protein, markers of granular cell differentiation. These divergent actions of Tg and CPA on distinct components of the keratinocyte differentiation program suggest that adequate intracellular Ca2+ stores are important for the expression of spinous cell proteins and inhibition of DNA synthesis, while elevation of Ca-1 stimulates the expression of markers of granular cell differentiation. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,CTR ONCOL,BALTIMORE,MD 21205. NR 67 TC 41 Z9 41 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD SEP PY 1995 VL 6 IS 9 BP 1171 EP 1184 PG 14 WC Cell Biology SC Cell Biology GA RU204 UT WOS:A1995RU20400015 PM 8519694 ER PT J AU ALBRIGHT, JW ZUNIGAPFLUCKER, JC ALBRIGHT, JF AF ALBRIGHT, JW ZUNIGAPFLUCKER, JC ALBRIGHT, JF TI TRANSCRIPTIONAL CONTROL OF IL-2 AND IL-4 IN T-CELLS OF YOUNG AND OLD MICE SO CELLULAR IMMUNOLOGY LA English DT Article ID MESSENGER-RNA EXPRESSION; MURINE LYMPHOCYTES-T; IMMUNE FUNCTION; AGED MICE; INTERLEUKIN-2 RECEPTOR; SIGNAL-TRANSDUCTION; ANTIGEN RECEPTOR; ELDERLY HUMANS; PROLIFERATION; ACTIVATION AB CD4+ T cells of aged compared to young subjects are defective in their responses to antigens and soluble mitogens. We asked whether or not there is a defect in the translocation of transcription factors (TF) in CD4+ T cells of aged mice. Electrophoretic mobility shift assays of three TF that regulate IL-2 gene expression, viz., Oct1/2, NF kappa B, and AP-1, in nuclear extracts of cells stimulated with immobilized anti-CD3 epsilon revealed no significant difference between cells of young and old mice. The nuclear levels of all three TF were lower in cells of both young and aged mice that were stimulated with Con A and lower in aged than in young. Similar assays of consensus sequences 1 and 2 (CS1 and CS2) TF involved in IL-4 gene transcription in cells of the Th2 subset revealed significant translocation of CS1 following stimulation of both young and aged cells with anti-CD3, more in cells of young than in those of aged mice. In contrast, the most evident effect of Con A stimulation was the accumulation of CS2 in nuclei of cells of aged mice. Apparently, there is no detrimental effect of senescence on the basic mechanisms of translocation of TF. The differences between stimulation with immobilized anti-CD3 epsilon and Con A can be explained by the relative abundance of memory-like CD4+ T cells which accumulate with age (and are defective in Ca2+ mobilization and signaling) and by the poor ability of memory-like cells in the aged to respond to CD28 costimulation. (C) 1995 Academic Press, Inc. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RP ALBRIGHT, JW (reprint author), GEORGE WASHINGTON UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,2300 I ST NW,WASHINGTON,DC 20037, USA. RI Zuniga-Pflucker, Juan/H-1295-2012; OI Zuniga-Pflucker, Juan Carlos/0000-0003-2538-3178 FU NIA NIH HHS [AG06278] NR 35 TC 15 Z9 15 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD SEP PY 1995 VL 164 IS 2 BP 170 EP 175 DI 10.1006/cimm.1995.1158 PG 6 WC Cell Biology; Immunology SC Cell Biology; Immunology GA RU196 UT WOS:A1995RU19600002 PM 7656324 ER PT J AU KUHNS, DB PRIEL, DAL GALLIN, JI AF KUHNS, DB PRIEL, DAL GALLIN, JI TI LOSS OF L-SELECTIN (CD62L) ON HUMAN NEUTROPHILS FOLLOWING EXUDATION IN-VIVO SO CELLULAR IMMUNOLOGY LA English DT Article ID ADHESION PROTEINS; HOMING RECEPTOR; CELL ACTIVATION; EXPRESSION; INFLAMMATION; RELEASE; INVIVO; MAC-1 AB L-selectin, an adhesion molecule expressed on the surface of peripheral blood neutrophils, mediates the rolling of neutrophils along vascular endothelium, Stimulation of neutrophils in vitro causes decreased expression of L-selectin on the surface of neutrophils due to shedding, In this study, we have demonstrated that human exudative neutrophils isolated from both skin lesions and from pus exhibit little expression of L-selectin, Although a dramatic accumulation of exudative neutrophils is observed in the skin lesions within 24 hr, there is no accompanying increase in soluble L-selectin. In addition, the levels of soluble L-selectin in the extracellular tissue fluid (97.2 +/- 12,7 mu g/ml, n = 8) are only 20% of that observed in peripheral plasma (482.4 +/- 35.9 mu g/ml). These data suggest that shedding of L-selectin from the surface of neutrophils occurs in the peripheral circulation as a prelude to diapedesis of neutrophils into peripheral tissues. (C) 1995 Academic Press, Inc. C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. NCI,FREDERICK RES & DEV CTR,SCI APPLICAT INT CORP FREDERICK,FREDERICK,MD 21702. NR 18 TC 22 Z9 23 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD SEP PY 1995 VL 164 IS 2 BP 306 EP 310 DI 10.1006/cimm.1995.1174 PG 5 WC Cell Biology; Immunology SC Cell Biology; Immunology GA RU196 UT WOS:A1995RU19600018 PM 7544694 ER PT J AU MAHONEY, CW SEKI, K HUANG, KP AF MAHONEY, CW SEKI, K HUANG, KP TI PHOSPHORYLATION OF MARCKS, NEUROMODULIN, AND NEUROGRANIN BY PROTEIN-KINASE-C EXHIBITS DIFFERENTIAL RESPONSES TO DIACYLGLYCEROLS SO CELLULAR SIGNALLING LA English DT Article DE PROTEIN KINASE C; DIACYLGLYCEROLS; MARCKS; NEUROMODULIN; NEUROGRANIN ID MEMBRANE PHOSPHOLIPIDS; PHOSPHATIDYLCHOLINE HYDROLYSIS; QUANTITATIVE MEASUREMENT; ACTIVATION; CELLS; SUBSTRATE; BRAIN; SN-1,2-DIACYLGLYCEROLS; PHOSPHATIDYLINOSITOL; DIGLYCERIDES AB Diacylglycerols (DG) derived from brain phosphatidylinositol (PI) and phosphatidylcholine (PC) and synthetic 1,2-dioleoylglycerol (diC(18:1)) and 1,2-dioctanoylglycerol (diC(8)) were tested for their efficacy in stimulating PKC-catalyzed phosphorylation of three physiological substrates in the brain, namely, MARCKS, neuromodulin (Nm), and neurogranin (Ng). The A(0.5) of these DGs for PKC were variable dependent on the protein substrates; the values were lowest with MARCKS and highest with Ng. With Ng as a substrate the A(0.5) of these DGs for PKC gamma were PI- and PC-DGs < diC(18:1) < diC(8). Both PI- and PC-DGs, in spite of their differences in unsaturated fatty acids content, were similarly effective in stimulating PKC. Since the phosphorylation of MARCKS, as compared to those of Nm and Ng, has the lowest A(0.5) With the various DGs, it seems that among these three PKC substrates MARCKS is most readily phosphorylated by PKCs following DG formation in vivo. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,METAB REGULAT SECT,BETHESDA,MD 20892. NR 39 TC 8 Z9 9 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD SEP PY 1995 VL 7 IS 7 BP 679 EP 685 DI 10.1016/0898-6568(95)00043-O PG 7 WC Cell Biology SC Cell Biology GA RW427 UT WOS:A1995RW42700005 PM 8519597 ER PT J AU COLBY, CL DUHAMEL, JR GOLDBERG, ME AF COLBY, CL DUHAMEL, JR GOLDBERG, ME TI OCULOCENTRIC SPATIAL REPRESENTATION IN PARIETAL CORTEX SO CEREBRAL CORTEX LA English DT Article ID FRONTAL EYE FIELDS; LATERAL INTRAPARIETAL AREA; MONKEY CEREBRAL-CORTEX; RHESUS-MONKEY; BEHAVIORAL ENHANCEMENT; COROLLARY DISCHARGE; SUPERIOR COLLICULUS; ASSOCIATION CORTEX; OCULOMOTOR SYSTEM; VISUAL RESPONSES AB Parietal cortex comprises several distinct areas. Neurons in each area are selective for particular stimulus dimensions and particular regions of space. The representation of space in a given area reflects a particular motor output by which a stimulus can be acquired. Neurons in the lateral intraparietal area (LIP) are active in relation to both visual and motor events. LIP neurons do not transmit an unambiguous saccadic command. Rather, they signal the location at which an event has occurred. These spatial locations are encoded in oculocentric coordinates, that is, with respect to the current or anticipated position of the center of gaze. When an eye movement brings the spatial location of a recently flashed stimulus into the receptive field of an LIP neuron, the neuron responds to the memory trace of that stimulus. This result indicates that, for nearly all LIP neurons, stored visual information is remapped in conjunction with saccades. Remapping of the memory trace maintains the alignment between the current image on the retina and the stored representation in cortex. Further, when an eye movement is about to occur, more than a third of LIP neurons transiently shift the location of their receptive fields. This anticipatory remapping allows the neuron to begin to respond to a visual stimulus even before the saccade is initiated that will bring the stimulus into the fixation-defined receptive field. Both kinds of remapping serve to create a constantly updated representation of stimulus location that is always in terms of distance and direction from the fovea. This oculocentric representation has the advantage that it already matches that known to exist in the frontal eye fields and the superior colliculus, the output targets of LIP, and it does not require further coordinate transformation in order to contribute to spatially accurate behavior. These results indicate that LIP can analyze visual space without ever forming a representation of absolute target position. C1 NEI,SENSORIMOTOR RES LAB,BETHESDA,MD 20892. NR 38 TC 184 Z9 184 U1 1 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD SEP-OCT PY 1995 VL 5 IS 5 BP 470 EP 481 DI 10.1093/cercor/5.5.470 PG 12 WC Neurosciences SC Neurosciences & Neurology GA RZ478 UT WOS:A1995RZ47800009 PM 8547793 ER PT J AU CURTIS, JF TOMER, K MCGOWN, S ELING, TE AF CURTIS, JF TOMER, K MCGOWN, S ELING, TE TI PROSTAGLANDIN-H SYNTHASE-CATALYZED RING OXYGENATION OF 2-NAPHTHYLAMINE - EVIDENCE FOR 2 DISTINCT OXIDATION PATHWAYS SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID AROMATIC-AMINES; ENDOPEROXIDE SYNTHETASE; ACTIVATION; METABOLISM; MICROSOMES; HYDROPEROXIDES; PURIFICATION; BIOSYNTHESIS; EPOXIDATION; CARCINOGEN AB Previous studies showed that prostaglandin H synthase (PHS) cooxidizes 2-naphthylamine (2-NA) to ring-oxygenated products. These metabolites are atypical for a peroxidase-mediated reaction and are completely different from the polymeric nonoxygenated metabolites of 2-NA that are generated with the model peroxidase horseradish peroxidase (HRP). In this study, we investigated possible explanations for the PHS-catalyzed formation of ring-oxygenated 2-NA metabolites. We found that introduction of a peroxyl radical-generated cosubstrate into the HRP/2-NA system resulted in the formation of the same ring-oxygenated products observed in the PHS/2-NA system. O-18(2) incorporation studies were utilized to further characterize the source of oxygen in the ring-oxygenated 2-NA metabolites. The data show that, in the ease of PHS, ring oxygenation can occur both by peroxyl radical-mediated attack on 2-NA and by direct transfer of peroxide oxygen from PHS to 2-NA. C1 NIEHS,RES TRIANGLE PK,NC 27709. RI Tomer, Kenneth/E-8018-2013 NR 24 TC 5 Z9 5 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD SEP PY 1995 VL 8 IS 6 BP 875 EP 883 DI 10.1021/tx00048a008 PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA RU205 UT WOS:A1995RU20500008 PM 7492737 ER PT J AU XU, QB LI, DG HOLBROOK, NJ UDELSMAN, R AF XU, QB LI, DG HOLBROOK, NJ UDELSMAN, R TI ACUTE HYPERTENSION INDUCES HEAT-SHOCK PROTEIN-70 GENE-EXPRESSION IN RAT AORTA SO CIRCULATION LA English DT Article DE HYPERTENSION; PROTEINS, HEAT SHOCK; AORTA; STRESS ID AGE-DEPENDENT RESPONSE; TRANSCRIPTION FACTOR; ADRENAL-CORTEX; STRESS; CELLS; INDUCTION; PRESSURE; STRETCH; BRAIN AB Background Many factors cause acute systemic hypertension, which in turn can result in damage to the vessel wall and lead to vascular disease. In previous studies, we demonstrated that restraint, or immobilization stress, results in the induction of heat-shock protein 70 (hsp70) gene expression in the aorta of adult rat and showed that this response was markedly attenuated with age. Methods and Results Here we provide evidence that restraint-induced hsp70 expression occurs secondary to a rise in systemic blood pressure. Old rats were unable to mount a significant stress-induced hypertensive response, providing an explanation for the reduced hsp70 response in the old rats. A variety of vasoactive agents that induce acute hypertension through distinct signal transduction pathways, including phenylephrine, dopamine, vasopressin, angiotensin II, and endothelin-1, were found to result in hsp70 mRNA induction in the aorta. The magnitude of hsp70 expression achieved with these hypertensive agents was directly correlated with their relative effects on blood pressure. Rats were treated with the vasodilator sodium nitroprusside, which prevented an acute rise in blood pressure from the hypertensive agents tested and abolished induction of hsp70 expression. Conclusions These findings support the conclusion that hsp70 induction occurs as a physiological response to acute hypertension and suggest the possibility that hsp70 plays a role in the protecting the vasculature from damage during hemodynamic stress. C1 JOHNS HOPKINS UNIV HOSP, DIV ENDOCRINE SURG, BALTIMORE, MD USA. RP NIA, GENE EXPRESS & AGING SECT, 4940 EASTERN AVE, BALTIMORE, MD 21224 USA. FU NIDDK NIH HHS [DK02064-04] NR 33 TC 87 Z9 91 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD SEP 1 PY 1995 VL 92 IS 5 BP 1223 EP 1229 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RR276 UT WOS:A1995RR27600025 PM 7648669 ER PT J AU SCHULICK, AH DONG, G NEWMAN, KD VIRMANI, R DICHEK, DA AF SCHULICK, AH DONG, G NEWMAN, KD VIRMANI, R DICHEK, DA TI ENDOTHELIUM-SPECIFIC IN-VIVO GENE-TRANSFER SO CIRCULATION RESEARCH LA English DT Article DE ENDOTHELIUM; GENE TRANSFER; ADENOVIRUS; CAROTID ARTERIES ID EXPRESSION; CELLS AB Targeted expression of genetic material within the vascular endothelium is potentially a powerful tool for the investigation of endothelial cell (EC) biology. We developed, optimized, and characterized an efficient somatic transgenic model of EC-specific gene transfer. Rat carotid arteries were infused with adenovirus expressing a beta-galactosidase (beta-gal) gene. The level and cell-type specificity of recombinant gene expression were measured by assaying beta-gal activity in vessel extracts and by counting transduced cells in histological sections. Toxicity was evaluated by counting total ECs (3 days) and by measuring neointimal formation (14 days). Effects of transduction on the proliferation of vascular cells were measured with bromodeoxyuridine and [H-3]thymidine. Maximum recombinant gene expression resulted from infusion of 1x10(10) to 1x10(11) plaque-forming units (pfu) per milliliter; approximate to 35% of luminal ECs were transduced. A high degree of EC specificity (90% to 98% of total transduced cells) was maintained over this range of virus concentrations. More highly concentrated virus resulted in loss of beta-gal expression and a large decrease in luminal EC number (97% decrease, P<.001). Gene transfer at 4x10(10) pfu/mL was efficient, preserved EC integrity, and caused minimal neointimal formation. After gene transfer, there were early (3-day) increases in both EC and smooth muscle cell proliferation. At 14 days, only EC proliferation remained elevated (18% versus 1.4% in vehicle-infused arteries, P=.005). This animal model permits efficient highly EC-specific gene transfer. Vascular toxicity is minimal, although the EC proliferative index is elevated. This model will be useful in experiments that elucidate the biological role of EC gene products and define pathways of EC gene regulation and signal transduction in vivo. C1 NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892. ARMED FORCES INST PATHOL,DEPT CARDIOVASC PATHOL,WASHINGTON,DC 20306. NR 30 TC 102 Z9 102 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD SEP PY 1995 VL 77 IS 3 BP 475 EP 485 PG 11 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA RQ825 UT WOS:A1995RQ82500003 PM 7641320 ER PT J AU CARELLA, AV MOSS, MW PROVOST, V QUINN, TC AF CARELLA, AV MOSS, MW PROVOST, V QUINN, TC TI A MANUAL BEAD ASSAY FOR THE DETERMINATION OF ABSOLUTE CD4(+) AND CD8(+) LYMPHOCYTE COUNTS IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED INDIVIDUALS SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID HIV-INFECTION AB CD4(+) T lymphocytes are currently the most common surrogate marker indicating disease progression in individuals infected with human immunodeficiency virus (HIV), Since the cost of enumerating lymphocyte phenotypes is quite high, an inexpensive bead assay analyzed by light microscopy (cytosphere assay; Coulter Corporation, Hialeah, Fla.) was developed as an alternative method for counting CD4(+) and CD8(+) T lymphocytes, To evaluate the reliability of the cytosphere assay, heparinized blood was collected from 117 HIV-infected individuals and tested for both CD4(+) and CD8(+) lymphocytes by flow cytometry and the cytosphere? assay. The Pearson correlation coefficient of the cytosphere assay compared with that of flow cytometry for CD4(+) T lymphocytes was 0.93, with mean values a standard deviations of 534 +/- 509 by flow cytometry and 499 +/- 477 by the cytosphere assay, The correlation coefficient for CD8(+) T lymphocytes was 0.86, with mean values of 831 +/- 543 by flow cytometry and 746 +/- 472 by the cytosphere assay, The sensitivity and specificity of the cytosphere assay in determining absolute CD4(+) T-lymphocyte counts of less than 200/mu l were 97.6 End 94.7%, respectively, The positive; predictive value was 90.9%; and the negative predictive value was 98.6%, The cytosphere assay was highly correlative to how cytometry in determining CD4(+) and CD8(+) T-lymphocyte counts among HN-infected patients, The ease and limited resources needed to perform this test make it ideal in developing countries and other areas where technology and finances are limited. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV INFECT DIS,BALTIMORE,MD 21205. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 8 TC 28 Z9 30 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD SEP PY 1995 VL 2 IS 5 BP 623 EP 625 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RU541 UT WOS:A1995RU54100018 PM 8548544 ER PT J AU Debinski, W Pastan, I AF Debinski, W Pastan, I TI Recombinant F(ab') C242-Pseudomonas exotoxin, but not the whole antibody-based immunotoxin, causes regression of a human colorectal tumor xenograft SO CLINICAL CANCER RESEARCH LA English DT Article ID SINGLE-CHAIN IMMUNOTOXINS; RICIN-A CHAIN; ESCHERICHIA-COLI; PSEUDOMONAS EXOTOXIN; MONOCLONAL-ANTIBODIES; ANTITUMOR-ACTIVITY; EXPRESSION; PROTEINS; GENES; MICE AB We have previously made a M(r) 195,000 immunotoxin (IT) composed of mAb C242 coupled to Pseudomonas exotoxin A, This IT inhibited growth but did not cause regression of a human colorectal cancer xenograft growing in nude mice (W. Debinski et al., J. Clin, Invest., 90: 405-411, 1992), Since smaller proteins penetrate into tissues and tumors better than larger proteins, we have made a smaller recombinant (r) IT to overcome the hypothesized poor tumor penetration of the M, 195,000 conjugate, This was accomplished by making a C242rF(ab')-based M(r) 86,000 IT, To make rF(ab')-IT, the Fd and kappa chains of mAb C242 were cloned, and kappa was fused at the gene level to PE38QQR, a mutant form of Pseudomonas exotoxin. Both C242Pd and C242 kappa-PE38QQR were expressed in a bacterial expression system, and large amounts of the C242Fd attached via a disulfide bond to the C242 kappa-PE38QQR were obtained, The C242rF(ab')-IT covalently linked heterodimer has a 50% inhibitory concentration of 0.2-2.0 ng/ml (2-20 pM, respectively) on human colon adenocarcinoma cell lines that express the C242 antigen, When injected into mice bearing Colo205 tumors, the C242rF(ab')-PE38QQR caused an immediate regression of the tumors, while the C242-PE38QQR conjugate had only a growth inhibitory effect, In addition, several cures were obtained, Our results indicate that rIT C242F(ab')-PE38QQR is a much more potent antitumor agent than an IgG conjugate. C1 HOP HOTEL DIEU,RES CTR,MOLEC TARGETING LAB,MONTREAL,PQ,CANADA. NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 32 TC 14 Z9 14 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP PY 1995 VL 1 IS 9 BP 1015 EP 1022 PG 8 WC Oncology SC Oncology GA TL084 UT WOS:A1995TL08400011 PM 9816074 ER PT J AU Benhar, I Pastan, I AF Benhar, I Pastan, I TI Characterization of B1(Fv)PE38 and B1(dsFv)PE38: Single-chain and disulfide-stabilized Fv immunotoxins with increased activity that cause complete remissions of established human carcinoma xenografts in nude mice SO CLINICAL CANCER RESEARCH LA English DT Article ID MONOCLONAL-ANTIBODIES; PSEUDOMONAS EXOTOXIN; RECOMBINANT IMMUNOTOXIN; VARIABLE DOMAINS; SELECTION; PROTEINS; RECEPTOR; GROWTH; TUMORS; CELLS AB The mAb B1 (mouse IgG1 kappa) recognizes a carbobydrate epitope on human carcinoma cells (I, Pastan et al., Cancer Res., 51: 3781-3787, 1991), We have generated plasmids encoding immunotoxins in which the Fv domain of B1, either as a single-chain Fv or as a disulfide-stabilized Fv (dsFv), was fused to PE38, a truncated form of Pseudomonas exotoxin A, To compare the activities of the two types of recombinant immunotoxins, the proteins were prepared from cytoplasmic inclusion bodies produced in Escherichia coli, The immunotoxins were evaluated for stability, antigen binding, specific cytotoxicity, pharmacokinetics, and antitumor activity in a nude mouse model, Although the single-chain immunotoxin is relatively stable when incubated at 37 degrees C (t1/2 similar to 4 h), the dsFv immunotoxin is much more stable, with no loss of activity after 8 h at 37 degrees C, The single-chain immunotoxin has a 2-fold better binding affinity and cytotoxicity toward antigen-positive cultured cells than the dsFv immunotoxin. The half-lives in the blood of mice of B1(Fv)PE38 (single-chain) and Bl(dsFv)PE38 (disulfide-stabilized) are 23 and 27 min, respectively, Their therapeutic potential was evaluated in athymic nude mice bearing human epidermoid carcinoma xenografts, Both immunotoxins caused complete regressions of the s.c. (30-40 mm(3)) tumors when given i.v. in three doses of 0.025 mg/kg every other day, This is one-twentieth of the mouse LD(50). Recombinant immunotoxins containing the B1(Fv) are 2-3-fold more potent antitumor agents than previously described immunotoxins containing the B3(Fv) (Brinkmann et al., Proc Natl, Acad. Sci USA, 88: 8616-8624 1991), which also target Le(Y) and related carbobydrates in human tumors, but have a similar toxicity in mice. Thus, their therapeutic window is 23-fold larger,In addition, B1(dsFv)PE38 has only a 50% decrease in the apparent binding affinity of B1(Fv)PE38, whereas B3(dsFv)PE38 has a much greater loss in antigen binding. C1 NCI,MOLEC BIOL LAB,DIV CANC BIOL DIAG & CTR,BETHESDA,MD 20892. NR 31 TC 27 Z9 27 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP PY 1995 VL 1 IS 9 BP 1023 EP 1029 PG 7 WC Oncology SC Oncology GA TL084 UT WOS:A1995TL08400012 PM 9816075 ER PT J AU Bagnato, A Tecce, R Moretti, C DiCastro, V Spergel, D Catt, KJ AF Bagnato, A Tecce, R Moretti, C DiCastro, V Spergel, D Catt, KJ TI Autocrine actions of endothelin-1 as a growth factor in human ovarian carcinoma cells SO CLINICAL CANCER RESEARCH LA English DT Article ID SMOOTH-MUSCLE CELLS; BREAST-CANCER CELLS; STROMAL CELLS; IMMUNOREACTIVE ENDOTHELIN-1; RECEPTOR SUBTYPES; MESSENGER-RNA; EXPRESSION; SECRETION; LINES; STIMULATION AB The production of endothelin 1 (ET-1) and its receptor-mediated actions on calcium signaling and growth responses were analyzed in human ovarian carcinoma cells. Immunoreactive ET-1 was released from three of four ovarian tumor cell lines as a function of time in amounts ranging from 56 to 74 fmol/10(6) cells. Reverse-phase HPLC and radioimmunoassay of conditioned media from tumor cells revealed a single peak coeluting with authentic ET-1. Radioligand binding studies showed that the ET-1-producing cell lines also expressed high-affinity ET(A) receptors (K-d < 0.1 nM) that ranged in abundance from 2,600 to 43,600 sites/cell. In fura-2-loaded ovarian carcinoma cells, ET-1 induced dose-dependent increases in cytoplasmic Ca2+ concentration. ET-1 also stimulated thymidine incorporation in the three cell lines that expressed ET receptors. In OVCA 433 cells, BQ 123 inhibited the stimulatory actions of ET-1 on thymidine incorporation and cell proliferation, and substantially reduced the basal growth rate of unstimulated ovarian tumor cells, These results demonstrate that ET-1 is produced in ovarian cancer cells and acts as an autocrine growth factor on ET, receptors to stimulate calcium signaling and proliferative responses, Such findings suggest that ET-1 participates in the progression of neoplastic growth in certain ovarian tumors. C1 UNIV ROMA TOR VERGATA,DEPT ANDROL,ROME,ITALY. UNIV ROMA TOR VERGATA,DEPT INTERNAL MED,ROME,ITALY. NIH,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. RP Bagnato, A (reprint author), REGINA ELENA INST CANC RES,MOLEC PATHOL & ULTRASTRUCT LAB,VIA MESSI ORO 156-158,I-00158 ROME,ITALY. RI Spergel, David/A-4410-2011; Bagnato, Anna/G-9747-2016; OI Bagnato, Anna/0000-0002-7269-9522; MORETTI, COSTANZO/0000-0003-4006-2575 NR 34 TC 95 Z9 96 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP PY 1995 VL 1 IS 9 BP 1059 EP 1066 PG 8 WC Oncology SC Oncology GA TL084 UT WOS:A1995TL08400017 PM 9816080 ER PT J AU SCHAFFER, R BOWERS, GN MELVILLE, RS AF SCHAFFER, R BOWERS, GN MELVILLE, RS TI HISTORY OF NISTS CONTRIBUTIONS TO DEVELOPMENT OF STANDARD REFERENCE MATERIALS AND REFERENCE AND DEFINITIVE METHODS FOR CLINICAL-CHEMISTRY SO CLINICAL CHEMISTRY LA English DT Article DE CALIBRATION; CALCIUM; CHLORIDE; CHOLESTEROL; CREATININE; GLUCOSE; LITHIUM; MAGNESIUM; POTASSIUM; SODIUM; TOTAL GLYCERIDES; TOTAL TRIGLYCERIDES; UREA; URIC ACID ID DILUTION-MASS-SPECTROMETRY; CANDIDATE REFERENCE METHOD; URIC-ACID; SERUM; CHOLESTEROL; FRAGMENTOGRAPHY; OPTIMIZATION; CREATININE; CALCIUM; GLUCOSE AB The issuance of cholesterol as a Standard Reference Material (SRM) in 1967, started the National Institute of Standards and Technology (NIST; then named the National Bureau of Standards) on a major effort to help clinical laboratories establish and improve the quality of measurements they make. NIST now issues three kinds of SRMs for that purpose: analyte samples of certified purity as primary standards, serum samples having certified analyte concentrations as accuracy controls, and materials certified for calibrating instruments. In working with clinical laboratory scientists to establish Reference Methods (RMs) for measuring the analytes, NIST developed Definitive Methods (DMs) to use for evaluating RM accuracy and then used the DMs for assigning analyte values to its SRMs. The development of SRMs and DMs is discussed. C1 HARTFORD HOSP,CLIN CHEM LAB,HARTFORD,CT 06115. NIH,CLIN CHEM STUDY SECT,BETHESDA,MD 20892. RP SCHAFFER, R (reprint author), NIST,CTR ANALYT CHEM,DIV ORGAN ANALYT RES,GAITHERSBURG,MD 20899, USA. NR 47 TC 9 Z9 10 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD SEP PY 1995 VL 41 IS 9 BP 1306 EP 1312 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA RT867 UT WOS:A1995RT86700009 PM 7656442 ER PT J AU LINDSAY, CK THORGEIRSSON, UP AF LINDSAY, CK THORGEIRSSON, UP TI LOCALIZATION OF MESSENGER-RNA FOR TISSUE INHIBITOR OF METALLOPROTEINASES-1 AND TYPE-IV COLLAGENASES/GELATINASES IN MONKEY HEPATOCELLULAR CARCINOMAS SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE FIBROSIS; HEPATOCELLULAR CARCINOMA; METALLOPROTEINASES; TISSUE INHIBITORS OF METALLOPROTEINASES ID GROWTH-FACTOR-BETA; HUMAN CANCER-CELLS; COLLAGENASE ACTIVITY; METALLO-PROTEINASES; COLORECTAL TUMORS; PLASMA-MEMBRANES; LIVER-CELLS; EXPRESSION; TIMP-1; DIFFERENTIATION AB Studies of tissue inhibitors of metalloproteinases (TIMPs) suggest that one of their main functions is to inhibit metalloproteinase (MMP) activity and thus prevent tumor invasion by preserving extracellular matrix (ECM) integrity. In the present study we examined the distribution of transcripts for TIMP-1, MMP-2 and MMP-9 in monkey hepatocellular carcinoma tissues. In situ hybridization demonstrated elevated levels of TIMP-1 transcripts in fibrous tissue septa, tumor inflammatory infiltrate, tumor blood vessels and in expanded portal areas. However, elevated transcripts for MMP-2 and MMP-9 were found only in tumor inflammatory infiltrate. In lung metastasis high levels of TIMP-1 transcripts were found in the stromal cells surrounding necrotic tumor nodules, in tumor blood vessels, and in mesothelial cells, MMP-9 transcripts were elevated at the periphery of the necrotic tumor nodules. These findings suggest that TIMP-1 and type IV collagenases/gelatinases can be independently regulated in vivo and that TIMP-1 may have functions in ECM remodeling which are unrelated to inhibition of MMP activity. C1 NCI,DIV CANC ETIOL,OFF DIRECTOR,TUMOR BIOL & CARCINOGENESIS SECT,BETHESDA,MD 20892. NR 38 TC 18 Z9 18 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD SEP PY 1995 VL 13 IS 5 BP 381 EP 388 PG 8 WC Oncology SC Oncology GA RN818 UT WOS:A1995RN81800007 PM 7641422 ER PT J AU GHABRAH, TM STRICKLAND, GT TSAREV, S YARBOUGH, P FARCI, P ENGLE, R EMERSON, S PURCELL, R AF GHABRAH, TM STRICKLAND, GT TSAREV, S YARBOUGH, P FARCI, P ENGLE, R EMERSON, S PURCELL, R TI ACUTE VIRAL-HEPATITIS IN SAUDI-ARABIA - SEROEPIDEMIOLOGICAL ANALYSIS, RISK-FACTORS, CLINICAL MANIFESTATIONS, AND EVIDENCE FOR A 6TH HEPATITIS AGENT SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ACUTE SPORADIC HEPATITIS; NON-B-HEPATITIS; C VIRUS-INFECTION; NON-A; POSTTRANSFUSION HEPATITIS; UNITED-STATES; ANTIBODY; ETIOLOGY; CHILDREN; ASSAY AB We conducted a prospective, descriptive cohort study of all 217 cases of acute viral hepatitis (AVH) seen in adults during 1992 at the sole hospitals with infectious disease departments in the second and third largest cities in the Kingdom of Saudi Arabia. In addition, we undertook a nested case-control study. Our goals were (1) to determine the causes, demographics, risk factors, and clinical characteristics of AVH in the Kingdom; (2) to evaluate the reliability of diagnostic tests for acute hepatitis C and E; and (3) to assess the relative importance, characteristics, and risk factors of a sixth hepatitis agent, non-A-E. All cases and controls completed a questionnaire. Cases provided blood samples for studies of serum bilirubin, alanine and aspartate aminotransferases, and antibody to hepatitis viruses as well as genome detection studies, The results of serological and molecular tests were used to categorize each case as hepatitis A, B, C, D, E, or non-A-E. Historical, clinical, and laboratory determinants were statistically analyzed by comparisons between groups with different types of AVH and controls. Analysis of risk factors suggested that hepatitis C and D were parenterally transmitted, while hepatitis A, E, and non-A-E were not; the route of transmission of hepatitis B was unclear. Hepatitis E was strongly associated with living or traveling on the Indian subcontinent, The clinical disease caused by all six agents was indistinguishable. The putative sixth agent caused 13% of cases. The second-generation tests for antibody to HCV and HEV were relatively reliable for the diagnosis of AVH. C1 UNIV MARYLAND, SCH MED, DEPT EPIDEMIOL & PREVENT MED, BALTIMORE, MD 21201 USA. KING ABDULAZIZ UNIV, COLL MED & ALLIED SCI, DEPT COMMUNITY MED & PRIMARY HLTH CARE, JEDDAH 21413, SAUDI ARABIA. UNIV MARYLAND, INT HLTH PROGRAM, BALTIMORE, MD USA. NIAID, INFECT DIS LAB, HEPATITIS VIRUSES SECT, BETHESDA, MD 20892 USA. GENELABS INC, SAN ANTONIO, TX USA. GEORGETOWN UNIV, MED CTR, DEPT MICROBIOL, DIV MOLEC VIROL & IMMUNOL, ROCKVILLE, MD USA. NR 31 TC 20 Z9 20 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP PY 1995 VL 21 IS 3 BP 621 EP 627 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RU940 UT WOS:A1995RU94000024 PM 8527554 ER PT J AU ASTHANA, S GREIG, NH HEGEDUS, L HOLLOWAY, HH RAFFAELE, KC SCHAPIRO, MB SONCRANT, TT AF ASTHANA, S GREIG, NH HEGEDUS, L HOLLOWAY, HH RAFFAELE, KC SCHAPIRO, MB SONCRANT, TT TI CLINICAL PHARMACOKINETICS OF PHYSOSTIGMINE IN PATIENTS WITH ALZHEIMERS-DISEASE SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID ORAL PHYSOSTIGMINE; SENILE DEMENTIA; MEMORY PROCESSES; CONTROLLED TRIAL; DOUBLE-BLIND; RAT; PHARMACODYNAMICS; CHOLINESTERASE; ARECOLINE; LECITHIN AB Objective: To study the pharmacokinetic and pharmacodynamic properties of physostigmine in subjects with Alzheimer's disease. Methods: Plasma physostigmine concentration and butyrylcholinesterase inhibition were measured in blood samples collected during and after a single high-dose (1 to 1.5 mg for 45 to 60 minutes) and a sustained low-dose steady-state intravenous infusion in nine subjects with Alzheimer's disease. Escalating doses (0.5 to 25 mg/day) were administered during a 2-week period, A dose (2 to 12 mg/day) that optimized cognition in each subject was identified and then administered in a randomized, double-blind, placebo-controlled crossover design for 1 week. Results: The elimination half-life of physostigmine was 16.4 +/- 3.2 (SE) minutes. Clearance and volume of distribution were 7.7 +/- 0.9 (SE) L/min and 2.4 +/- 0.6 (SE) L/kg, respectively. Butyrylcholinesterase inhibition half-life was 83.7 +/- 5.2 (SE) minutes. During sustained steady-state infusion, plasma physostigmine concentration (r = 0.95) and butyrylcholinesterase inhibition (r = 0.99) were linearly correlated with the dose. In five cognitive responders, the memory enhancement was significantly correlated (r = 0.86; p < 0.05) with butyrylcholinesterase inhibition. Conclusions: These results showed that, in cognitive responders, memory enhancement by physostigmine in Alzheimer's disease is correlated directly to the magnitude of plasma cholinesterase inhibition, Furthermore, during single-dose conditions, the dynamic half-life is five-fold longer than the kinetic half-life. C1 NIA,NEUROSCI LAB,BETHESDA,MD 20892. NR 50 TC 41 Z9 41 U1 1 U2 4 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD SEP PY 1995 VL 58 IS 3 BP 299 EP 309 DI 10.1016/0009-9236(95)90246-5 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RZ006 UT WOS:A1995RZ00600007 PM 7554703 ER PT J AU RIZZO, LV CASPI, RR AF RIZZO, LV CASPI, RR TI IMMUNOTOLERANCE AND PREVENTION OF OCULAR AUTOIMMUNE-DISEASE SO CURRENT EYE RESEARCH LA English DT Review ID MYELIN BASIC-PROTEIN; T-CELL RECEPTOR; GROWTH-FACTOR-BETA; INDUCED IMMUNE DEVIATION; ANTERIOR-CHAMBER; TRANSPLANTATION IMMUNOLOGY; HELPER LYMPHOCYTES; IDIOTYPIC NETWORK; UVEORETINITIS EAU; ORAL TOLERIZATION AB Immunotherapeutic approaches to autoimmune disease have a common goal of inducing antigen-specific, long-lasting tolerance to autoantigens, without otherwise compromising the immune response. Here we review some of the most interesting experimental advances in this area. We discuss the use of T cell targeting drugs that have been reported to induce long lasting tolerance to ocular antigens. Strategies involving the targeting of idiotypic and clonotypic determinants associated with ocular autoimmunity, such as idiotypic network manipulation and T cell vaccination, are reviewed. The use of cytokines to promote perturbation of the Th1/Th2 balance with its possible implications for treatment of uveitis, is analysed. Finally, we review tolerogenic strategies based on acquisition of tolerance following presentation of antigen through alternative routes, such as injection of antigen into the anterior chamber, intravenous infusion of antigen, and oral administration of retinal antigens. Special emphasis is placed on the last strategy, since there are ongoing clinical trials using oral tolerance as an immunotherapeutic approach to treat autoimmune diseases, among them uveitis. RP RIZZO, LV (reprint author), NEI,IMMUNOL LAB,IMMUNOREGULAT SECT,BLDG 10,9000 ROCKVILLE PIKE,ROOM 10N202,BETHESDA,MD 20892, USA. RI Rizzo, Luiz Vicente/B-4458-2009 NR 99 TC 9 Z9 9 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD SEP PY 1995 VL 14 IS 9 BP 857 EP 864 DI 10.3109/02713689508995809 PG 8 WC Ophthalmology SC Ophthalmology GA RW141 UT WOS:A1995RW14100015 PM 8529426 ER PT J AU JENSEN, RT AF JENSEN, RT TI PANCREATIC ENDOCRINE TUMORS SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article AB Pancreatic endocrine tumors (PETs) can either be functional, and associated with a specific clinical syndrome due to the hormone excess, or nonfunctional. Because all PETs, except insulinoma, are malignant in more than 50% of cases, PETs require treatment directed at both the tumor and the hormone excess state. This review focuses on advances reported within the past year. The following areas are covered: insights into the clinical aspects and genetic basis of PETs associated with various inherited diseases; advances in tumor localization; recent insights into tumor biological behavior, pathology, and possible genetic alterations associated with malignancy; recent insights or advances in the diagnosis or clinical course of individual syndromes; and advances in both surgical and medical treatment of localized and advanced disease. RP JENSEN, RT (reprint author), NIDDK,DIGEST DIS BRANCH,BLDG 10,ROOM 9C-103,10 CTR DR,MSC 1804,BETHESDA,MD 20892, USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD SEP PY 1995 VL 11 IS 5 BP 423 EP 429 DI 10.1097/00001574-199509000-00006 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RV297 UT WOS:A1995RV29700006 ER PT J AU STRADER, DB BENJAMIN, SB LUBENSKY, TA GIBRIL, F WEBER, C FISHBEYN, VA JENSEN, RT METZ, DC AF STRADER, DB BENJAMIN, SB LUBENSKY, TA GIBRIL, F WEBER, C FISHBEYN, VA JENSEN, RT METZ, DC TI ESOPHAGEAL FUNCTION AND OCCURRENCE OF BARRETTS-ESOPHAGUS IN ZOLLINGER-ELLISON SYNDROME SO DIGESTION LA English DT Article DE ISLET CELL TUMOR; PANCREATIC ENDOCRINE TUMOR; ESOPHAGEAL REFLUX; BARRETTS ESOPHAGUS; ZOLLINGER-ELLISON SYNDROME ID GASTROESOPHAGEAL REFLUX DISEASE; GASTRIC-ACID SECRETION; SPHINCTER; COMPLICATIONS; MANAGEMENT; MECHANISMS; RESECTION; MANOMETRY; FREQUENT; SYMPTOMS AB Manifestations of esophageal disease are present in up to 60% of patients with Zollinger-Ellison syndrome (ZES), although esophageal function has been studied in only a few patients and the prevalence of Barrett's mucosa is unknown in these patients. It is unclear whether the high prevalence of esophageal disease is related to gastric acid hypersecretion alone or to abnormalities of esophageal motility or lower esophageal sphincter (LES) function in addition. To address these issues in the present study esophageal function was evaluated prospectively in 92 consecutive patients with ZES (66 with active disease, 26 disease-free after curative resection) seen during a 1-year period after controlling acid hypersecretion. In the patients with active disease the mean basal acid output (BAG) was 33 +/- 3.0 mEq/h, the maximal acid output (MAO) was 56 +/- 4.0 mEq/h, fasting serum gastrin was 8,736 +/- 4,813 pg/ml and duration of disease prior to study was 12.5 +/- 2.0 years. At the time of manometry, gastric acid secretion was controlled in all patients and no patient had evidence of gastroesophageal reflux disease at upper gastrointestinal endoscopy. Esophageal manometry revealed normal motility in 85% of patients. Eleven percent had low LES pressures, and only 1% of patients had an elevated LES pressure. The frequency of Barrett's mucosa (3%) was similar to that found in the general population but much less than that reported in patients with idiopathic GERD. No correlation was noted between LES pressures or manometric abnormalities and the fasting serum gastrin, BAG, MAO or the presence or absence of multiple endocrine neoplasia type I or previous vagotomy. Esophageal manometric results and LES pressure were similar in disease-free patients and those with active ZES. In conclusion, these results suggest that hypergastrinemia or other disease-specific abnormalities are not contributing to the high incidence of esophageal disease in patients with ZES because esophageal function in patients with ZES is similar to normals. Specifically, motility disorders in patients with ZES occur in similar frequency to normals, and LES pressure is normal in most patients. Despite the high levels of acid secretion and prominence of symptoms, the occurrence of Barrett's mucosa was uncommon (3%) raising the possibility of additional protective mechanisms in patients with ZES. C1 NIDDKD, DIGEST DIS BRANCH, BETHESDA, MD 20892 USA. NCI, PATHOL LAB, BETHESDA, MD 20892 USA. GEORGETOWN UNIV HOSP, DIV GASTROENTEROL, WASHINGTON, DC 20007 USA. NR 68 TC 22 Z9 22 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0012-2823 EI 1421-9867 J9 DIGESTION JI Digestion PD SEP-OCT PY 1995 VL 56 IS 5 BP 347 EP 356 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RV536 UT WOS:A1995RV53600002 PM 8549876 ER PT J AU BADIO, B SHI, D GARRAFFO, HM DALY, JW AF BADIO, B SHI, D GARRAFFO, HM DALY, JW TI ANTINOCICEPTIVE EFFECTS OF THE ALKALOID EPIBATIDINE - FURTHER-STUDIES ON INVOLVEMENT OF NICOTINIC RECEPTORS SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE CALCIUM CHANNELS; GANGLIONIC BLOCKERS; ACETYLCHOLINE; CAFFEINE; NICOTINE ID CENTRAL-NERVOUS-SYSTEM; MOUSE-BRAIN; INDUCED ANALGESIA; RAT; CALCIUM; ACETYLCHOLINE; ANTAGONISM; RELEASE; MICE; SYNAPTOSOMES AB Epibatidine is a potent analgetic agent with high affinity for nicotinic receptors. The antinociceptive effects of epibatidine are blocked by both competitive and noncompetitive nicotinic antagonists. The L-type calcium channel activator Bay K 8644 potentiates the antinociceptive effects of epibatidine, while nifedipine antagonizes the antinociceptive effects. Acute treatment with chlorisondamine leads to long-term blockade of the antinociceptive effects of epibatidine. The antinociceptive effects of epibatidine are reduced in mice rendered tolerant to the behavioral effects of nicotine by chronic nicotine or caffeine treatment. Epibatidine has very high affinity for the major central nicotinic receptor to which [H-3]nicotine binds. However, unlike nicotine and cytisine, epibatidine is very potent at ganglionic-type nicotinic receptors. Epibatidine in cultured cells causes desensitization of both ganglionic and neuromuscular nicotinic receptors. Thus, like nicotine, chronic treatment with epibatidine might be expected to lead to tolerance. These studies establish epibatidine as a tool for the study of nicotinic pathways involved in pain perception. (C) 1995 Wiley-Liss, Inc. RP BADIO, B (reprint author), NIDDKD,BIOORGAN CHEM LAB,BLDG 8,RM 1A17,BETHESDA,MD 20892, USA. NR 59 TC 44 Z9 44 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 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD SEP PY 1995 VL 36 IS 1 BP 46 EP 59 DI 10.1002/ddr.430360108 PG 14 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RX562 UT WOS:A1995RX56200007 ER PT J AU MENOTTIRAYMOND, M OBRIEN, SJ AF MENOTTIRAYMOND, M OBRIEN, SJ TI HYPERVARIABLE GENOMIC VARIATION TO RECONSTRUCT THE NATURAL-HISTORY OF POPULATIONS - LESSONS FROM THE BIG CATS SO ELECTROPHORESIS LA English DT Article; Proceedings Paper CT 3rd International Conference on DNA Fingerprinting CY DEC 13-16, 1994 CL HYDERABAD, INDIA ID NORTH-AMERICAN ZOOS; GENETIC DIVERSITY; AFRICAN CHEETAH; DOMESTIC CAT; KINSHIP; LIONS; MAP AB The extent and nature of variation in hypervariable regions of DNA have been used in the past as a means to infer the natural histories of populations. We review the interpretation of the extent of genetic diversity for minisatellite DNA in the cheetah to estimate the timing of a population bottleneck in the species and the potential application of a second class of hypervariable DNA, microsatellite DNA, as a molecular tool to examine the natural histories of felid populations. A calibration curve relating the degree of allele fragment sharing in individuals to relatedness in a captive pedigree of cheetahs is presented. This measurement has important applications for management of potential matings in captive management situations. RP MENOTTIRAYMOND, M (reprint author), NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. NR 39 TC 11 Z9 14 U1 3 U2 8 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 SEP PY 1995 VL 16 IS 9 BP 1771 EP 1774 DI 10.1002/elps.11501601293 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA TD110 UT WOS:A1995TD11000039 PM 8582370 ER PT J AU PHILLIP, M SEGEVE, Y ZUNG, A KOWARSKI, AA WERNER, H ROBERTS, CT LEROITH, D LADAS, J MULRONEY, SE AF PHILLIP, M SEGEVE, Y ZUNG, A KOWARSKI, AA WERNER, H ROBERTS, CT LEROITH, D LADAS, J MULRONEY, SE TI THE ACCUMULATION OF IGF-I IN KIDNEYS OF STREPTOZOTOCIN-DIABETIC ADULT-RATS IS NOT ASSOCIATED WITH ELEVATED PLASMA GH OR IGF-I LEVELS SO ENDOCRINE LA English DT Article DE DIABETES; KIDNEY; IGF-I; GROWTH HORMONE; RAT ID GROWTH FACTOR-I; GLOMERULAR-FILTRATION RATE; RENAL HYPERTROPHY; IMMATURE RATS; UNILATERAL NEPHRECTOMY; FACTOR ANTAGONIST; GENE-EXPRESSION; RECEPTOR GENE; HORMONE; SOMATOSTATIN AB Nephropathy is a major complication of diabetes mellitus and is associated with expansion of the mesangium and an increase in kidney size in both humans and rats. Interestingly, early kidney enlargement occurs only in postpubertal animals, and is preceded by a significant increase in the levels of extractable renal IGF-I. This study examined the possibility that this difference is CH dependent, and that very early changes in plasma GH and/or ICF-I in the adult animal are associated with an early accumulation of renal IGF-I. Silastic jugular catheters were placed in adult (13-14 week) male Sprague-Dawley (S-D) rats for blood collection and drug injection. Serial blood samples were taken every 30 min in groups of saline control and streptozotocin (STZ) (50 mu g/kg, IV) rats from 1-6 h, 9-15 h, and 24-30 h post-injection, and plasma GH profiles were determined by RIA. Renal ICF-I content was assessed following acid extraction. Following STZ, there was an immediate, step-wise reduction in peak GH levels (saline controls, 54 +/- 7 ng/ml vs 30 +/- 5 (1-6 h); 23 +/- 10 (9-15 h); and 13 +/- 3 ng/ml (24-30 h post-STZ); P<0.05 for all STZ groups vs control). The same significant step-wise reduction was observed in the integrated area under the curve for GH. A separate group of rats were treated with a GH-releasing factor antagonist (CRF-AN) for 5 days prior to STZ, to suppress pulsatile GH release, and reduce plasma IGF-I. Chronic CRF-AN administration reduced plasma IGF-l levels significantly to 63% of control values (P<0.01). However, despite the reduction in plasma IGF-I, renal IGF-I remained significantly elevated 24 h post-STZ compared with controls and not significantly different from animals treated with STZ alone (467 +/- 49 ng IGF-I/g KW in control saline vs 778 +/- 100 in saline/STZ and 705 +/- 87 ng ICF-I/g KW in chronic GRF-AN/STZ rats (P<0.05)). In conclusion, following STZ administration in the adult rat, there is an immediate reduction in CH levels, indicating the renal IGF-I accumulation occurs without initial increases in plasma GH levels. Furthermore, when plasma IGF-I levels in the adult are significantly reduced renal IGF-I content remains elevated. These data suggest that early diabetic renal growth is not associated with elevated circulating GH levels, and that high basal plasma IGF-I levels are not necessary for IGF-I accumulation. C1 GEORGETOWN UNIV,SCH MED,DEPT PHYSIOL & BIOPHYS,WASHINGTON,DC 20007. BEN GURION UNIV NEGEV,FAC HLTH SCI,SOROKA MED CTR,DEPT PEDIAT,BEER SHEVA,ISRAEL. UNIV MARYLAND,DIV PEDIAT ENDOCRINOL,BALTIMORE,MD 21201. NIDDK,CELLULAR & MOLEC PHYSIOL SECT,DIABET BRANCH,BETHESDA,MD. OI Roberts, Charles/0000-0003-1756-5772 NR 30 TC 5 Z9 5 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07012 SN 0969-711X J9 ENDOCRINE JI Endocrine PD SEP PY 1995 VL 3 IS 9 BP 689 EP 693 DI 10.1007/BF02746346 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RX950 UT WOS:A1995RX95000009 PM 21153228 ER PT J AU SMITH, MA MAKINO, S KIM, SY KVETNANSKY, R AF SMITH, MA MAKINO, S KIM, SY KVETNANSKY, R TI STRESS INCREASES BRAIN-DERIVED NEUROTROPIC FACTOR MESSENGER-RIBONUCLEIC-ACID IN THE HYPOTHALAMUS AND PITUITARY SO ENDOCRINOLOGY LA English DT Article ID NERVE GROWTH-FACTOR; CORTICOTROPIN-RELEASING FACTOR; RAT-BRAIN; CHOLINERGIC NEURONS; ADRENOCORTICAL AXIS; ANTERIOR-PITUITARY; RNA; BDNF; EXPRESSION; RECEPTORS AB Brain-derived neurotropic factor (BDNF) is a member of the nerve growth factor family that is important for neuronal survival and plasticity. We recently demonstrated that stress decreases BDNF messenger RNA (mRNA) levels in the hippocampus, which raises the possibility that BDNF may play a role in regulation of the hypothalamic-pituitary-adrenal axis. The purpose of this study was to determine whether BDNF expression is present and influenced by stress in other brain areas relevant to control of the hypothalamic-pituitary-adrenal axis. Using in situ hybridization, we found that BDNF mRNA is present in the parvocellular portion of the hypothalamic paraventricular nucleus (PVN), the lateral hypothalamus, and the anterior and neurointermediate lobes of the pituitary in rats. Acute (2-h) or repeated immobilization stress increased BDNF mRNA in all of these areas. This was in distinct contrast to stress-induced decreases in extrahypothalamic areas, including the basolateral amygdala, claustrum, and cingulate cortex as well as the hippocampus. BDNF was expressed in both CRF and TRH neurons in the PVN. Reducing glucocorticoid or thyroid negative feedback increased BDNF mRNA in the PVN and anterior pituitary, but not in the neurointermediate lobe. These results suggest that BDNF is a stress-responsive intercellular messenger that may be an important component of the stress response. C1 NIMH, CLIN NEUROL BRANCH, BETHESDA, MD 20892 USA. SLOVAK ACAD SCI, INST EXPTL ENDOCRINOL, BRATISLAVA, SLOVAKIA. RP SMITH, MA (reprint author), NIMH, BIOL PSYCHIAT BRANCH, BLDG 10, ROOM 3N212, 900 ROCKVILLE PK, BETHESDA, MD 20892 USA. NR 43 TC 175 Z9 176 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 SEP PY 1995 VL 136 IS 9 BP 3743 EP 3750 DI 10.1210/en.136.9.3743 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RQ622 UT WOS:A1995RQ62200008 PM 7649080 ER PT J AU JOSHI, L MURATA, Y WONDISFORD, FE SZKUDLINSKI, MW DESAI, R WEINTRAUB, BD AF JOSHI, L MURATA, Y WONDISFORD, FE SZKUDLINSKI, MW DESAI, R WEINTRAUB, BD TI RECOMBINANT THYROTROPIN CONTAINING A BETA-SUBUNIT CHIMERA WITH THE HUMAN CHORIONIC GONADOTROPIN-BETA CARBOXY-TERMINUS IS BIOLOGICALLY-ACTIVE, WITH A PROLONGED PLASMA HALF-LIFE - ROLE OF CARBOHYDRATE IN BIOACTIVITY AND METABOLIC-CLEARANCE SO ENDOCRINOLOGY LA English DT Article ID ASPARAGINE-LINKED OLIGOSACCHARIDES; HAMSTER OVARY CELLS; ALPHA-SUBUNIT; GLYCOPROTEIN HORMONES; STIMULATING-HORMONE; SULFATION; LUTROPIN; RECEPTOR; FOLLITROPIN; EXPRESSION AB Recombinant TSH is now successfully being used in clinical studies of thyroid cancer. Because of its therapeutic potential, we have constructed a longer acting analog of TSH by fusing the carboxy-terminal extension peptide (CTEP) of hCG beta onto TSH beta. When coexpressed either with alpha-subunit complementary DNA or a minigene in African green monkey (COS-7) and human embryonic kidney (293) cells, the chimera was fully bioactive in vitro and exhibited enhanced in vivo potency associated with a prolonged plasma half-life. The addition of 25 amino acids with 4 O-linked oligosaccharide chains did not affect the assembly and secretion of chimeric TSH. Wild-type (WT) and chimeric TSH secreted by COS-7 and 293 cells displayed wide differences in their plasma half-lives, presumably due to the presence of terminal sialic acid and SO4 on their oligosaccharide chains, respectively. Chimeric and WT TSH secreted by both cell lines demonstrated similar bioactivity in cAMP production, with some differences in [H-3]thymidine incorporation. Chimeric TSH appears to be more effective in COS-7 cells than in 293 cells, as judged by growth assay. COS-7-produced chimeric TSH showed the maximum increase in half-life, indicating the importance of sialic acid in prolonging half-life and in vivo potency. Sulfation of both subunits, predominantly beta and to a lesser extent alpha, appears to be responsible at least in part for the increased metabolic clearance of WT and chimeric TSH secreted by 293 cells. Apart from its therapeutic potential, chimeric TSH produced in various cell lines can be used as a tool to delineate the roles of sulfate and sialic acid in the in vivo clearance and, thereby, the in vivo bioactivity. C1 BETH ISRAEL HOSP, THYROID UNIT, BOSTON, MA 02215 USA. UNIV MASSACHUSETTS, MED CTR, DIV ENDOCRINOL, WORCESTER, MA 01655 USA. RP JOSHI, L (reprint author), NIDDK, MOLEC & CELLULAR ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NR 46 TC 51 Z9 51 U1 0 U2 2 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 SEP PY 1995 VL 136 IS 9 BP 3839 EP 3848 DI 10.1210/en.136.9.3839 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RQ622 UT WOS:A1995RQ62200020 PM 7544273 ER PT J AU LUO, X KISS, A RABADANDIEHL, C AGUILERA, G AF LUO, X KISS, A RABADANDIEHL, C AGUILERA, G TI REGULATION OF HYPOTHALAMIC AND PITUITARY CORTICOTROPIN-RELEASING HORMONE-RECEPTOR MESSENGER-RIBONUCLEIC-ACID BY ADRENALECTOMY AND GLUCOCORTICOIDS SO ENDOCRINOLOGY LA English DT Article ID FACTOR CRF RECEPTORS; MEDIAN-EMINENCE; ADRENOCORTICOTROPIN SECRETION; PARAVENTRICULAR NUCLEUS; RAT-BRAIN; VASOPRESSIN; STRESS; AXIS; RESPONSES; RNA AB The effects of adrenalectomy and glucocorticoids on the regulation of corticotropin-releasing hormone (CRH) receptor expression in the hypothalamic paraventricular nucleus (PVN) and pituitary were studied by in situ hybridization in the rat using a complementary RNA probe directed toward the coding region of the type 1 CRH receptor. Eighteen hours after adrenalectomy, CRH receptor messenger RNA (mRNA) expression in the PVN was significantly increased, whereas longer term adrenalectomy (4 and 6 days) had no effect. This transient effect of adrenalectomy was prevented by glucocorticoid replacement. In intact rats, 4 h after immobilization for 1 h or a single ip hypertonic saline injection, CRH receptor mRNA in the PVN markedly increased (P < 0.01), an effect that was unchanged by adrenalectomy (4 or 6 days) or dexamethasone injection (100 mu g at -14 and 50 mu g at -1 h) before stress. In the pituitary, CRH receptor mRNA levels decreased transiently after adrenalectomy (-62% after 18 h), returning to basal levels 4 or 6 days after adrenalectomy. The early decrease was prevented by glucocorticoid replacement. In intact rats, dexamethasone (100 mu g, sc) caused a significant decrease in pituitary CRH receptor mRNA levels 2-10 h after injection, returning to basal levels after 15 h. On the other hand, dexamethasone (5-300 mu g, sc) had no effect on pituitary CRH receptor mRNA levels 18 h after injection. The data show that although stress stimulation of CRH mRNA in the PVN is glucocorticoid independent, basal levels are likely to be under dual, transcriptional and posttranscriptional, control by glucocorticoids. In the pituitary, changes in hypothalamic CRFs probably play a major role in the control of CRH receptor mRNA levels during manipulations of circulating glucocorticoids levels. In addition, the inability of long term adrenalectomy and glucocorticoid administration to modify pituitary CRH receptor mRNA levels suggests that CRH receptor down-regulation observed under these experimental conditions depends mainly on translational and posttranslational events rather than receptor mRNA levels. C1 NICHHD, DEV BIOL BRANCH, SECT ENDOCRINE PHYSIOL, BETHESDA, MD 20892 USA. NR 41 TC 55 Z9 56 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1995 VL 136 IS 9 BP 3877 EP 3883 DI 10.1210/en.136.9.3877 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RQ622 UT WOS:A1995RQ62200025 PM 7649095 ER PT J AU MARTINEZLACACI, I SACEDA, M PLOWMAN, GD JOHNSON, GR NORMANNO, N SALOMON, DS DICKSON, RB AF MARTINEZLACACI, I SACEDA, M PLOWMAN, GD JOHNSON, GR NORMANNO, N SALOMON, DS DICKSON, RB TI ESTROGEN AND PHORBOL ESTERS REGULATE AMPHIREGULIN EXPRESSION BY 2 SEPARATE MECHANISMS IN HUMAN BREAST-CANCER CELL-LINES SO ENDOCRINOLOGY LA English DT Article ID PROTEIN-KINASE-C; EPIDERMAL GROWTH-FACTOR; MESSENGER-RNA; GENE-TRANSCRIPTION; FACTOR-ALPHA; MCF-7 CELLS; SIGNAL-TRANSDUCTION; NUCLEOTIDE-SEQUENCE; ENHANCER ELEMENTS; EPITHELIAL-CELLS AB The actions of 17 beta-estradiol (E(2)) and protein kinase C (PKC) appear to converge in the regulation of expression of certain growth modulatory genes, such as the growth factor amphiregulin (AR). AR is known to modulate cell growth by binding to the epidermal growth factor receptor. In the current report we established the mechanisms of the PKC-activating phorbol ester tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA) and the steroid hormone E(2) on the induction of AR expression in human breast carcinoma cell lines. TPA (100 nM) and E(2) (1 nM) induce AR messenger RNA(mRNA) expression by 6- to 8-fold and 3- to 6-fold, respectively, in a time- and dose-dependent manner. In addition, immunoreactive AR protein is induced by both TPA and E(2) by 6- to 8-fold and 2- to 4-fold, respectively. The PKC-modulating drugs, bryostatin and H-7, and antiestrogens (ICI 164,384 and 4-hydroxytamoxifen) interfere with AR induction by TPA and estrogen, respectively. The effects of TPA and E(2) on the induction of AR mRNA were both closely associated with enhanced transcription of the AR gene. However, TPA had an additional effect at the posttranscriptional level by stabilizing the AR mRNA. The protein synthesis inhibitor, cycloheximide, prevented AR induction by TPA, suggesting that a component of the TPA induction of AR is indirect and dependent upon protein synthesis. Conversely, the E(2) induction of AR transcription was found to be a direct response, independent of protein synthesis. The results presented herein thus demonstrate that TPA and E(2) are able to stimulate AR gene transcription by two separate mechanisms. C1 GEORGETOWN UNIV, VINCENT T LOMBARDI CANC RES CTR, WASHINGTON, DC 20007 USA. GEORGETOWN UNIV, DEPT CELL BIOL, WASHINGTON, DC 20007 USA. SUGEN INC, REDWOOD CITY, CA 94063 USA. US FDA, DIV CYTOKINE BIOL, BETHESDA, MD 20892 USA. NCI, TUMOR IMMUNOL & BIOL LAB, TUMOR GROWTH FACTOR SECT, BETHESDA, MD 20892 USA. RI Saceda, Miguel/A-1581-2008; PLOWMAN, Greg/E-2012-2011 NR 72 TC 61 Z9 62 U1 1 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1995 VL 136 IS 9 BP 3983 EP 3992 DI 10.1210/en.136.9.3983 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RQ622 UT WOS:A1995RQ62200037 PM 7649107 ER PT J AU MARTINEZ, A MILLER, MJ UNSWORTH, EJ SIEGFRIED, JM CUTTITTA, F AF MARTINEZ, A MILLER, MJ UNSWORTH, EJ SIEGFRIED, JM CUTTITTA, F TI EXPRESSION OF ADRENOMEDULLIN IN NORMAL HUMAN LUNG AND IN PULMONARY TUMORS SO ENDOCRINOLOGY LA English DT Article ID HYPOTENSIVE PEPTIDE; CLONING; CANCER; CDNA AB Adrenomedullin (AM) is a potent hypotensive peptide recently discovered in extracts of human pheochromocytoma. In this report we present evidence, using reverse transcriptase-polymerase chain reaction, immunocytochemistry, and in situ reverse transcriptase-polymerase chain reaction, that AM is synthesized by several cell populations of the normal lung, tumor cell lines of pulmonary origin, and tumor specimens. Among the normal cell populations of the lung, we found AM expression in the columnar epithelium, some glands, neurons of the pulmonary parasympathetic nervous system, endothelial cells, chondrocytes, alveolar macrophages, and smooth muscle cells. In tumors, AM expression was located in most of the nonsmall cell lung carcinomas and in half of the small cell lung carcinomas studied. These findings suggest that AM may play a broad role in respiratory homeostasis and lung carcinogenesis. C1 UNIV PITTSBURGH, DEPT PHARMACOL, PITTSBURGH, PA 15261 USA. RP MARTINEZ, A (reprint author), NCI, DIV CANC PREVENT & CONTROL, BIOMARKERS & PREVENT RES BRANCH, 9610 MED CTR DR, ROOM 300, ROCKVILLE, MD 20850 USA. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 37 TC 179 Z9 182 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1995 VL 136 IS 9 BP 4099 EP 4105 DI 10.1210/en.136.9.4099 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RQ622 UT WOS:A1995RQ62200051 PM 7649118 ER PT J AU KARALIS, K MASTORAKOS, G SANO, H WILDER, RL CHROUSOS, GP AF KARALIS, K MASTORAKOS, G SANO, H WILDER, RL CHROUSOS, GP TI SOMATOSTATIN MAY PARTICIPATE IN THE ANTIINFLAMMATORY ACTIONS OF GLUCOCORTICOIDS SO ENDOCRINOLOGY LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; TUMOR NECROSIS FACTOR; RAT SPINAL-CORD; SUBSTANCE-P; MEDULLA-OBLONGATA; NEUROPEPTIDES; INFLAMMATION; EXPRESSION; RECEPTORS; SECRETION AB Glucocorticoids are potent antiinflammatory agents. They inhibit leukocyte chemotaxis and vascular permeability and generally suppress the expression of many inflammatory mediators. Recent reports suggested that somatostatin (Sms) had significant immunomodulatory properties in vitro and in vivo. In this study we examined the effects of glucocorticoids on immunoreactive somatostatin expression in aseptic inflammatory sites of Sprague-Dawley rats given carrageenin sc. The progress of the inflammatory reaction was studied over a 7-h period with respect to the volume and cellularity of the exudate and the levels of the inflammatory mediators expressed in the inflammatory site, including immunoreactive substance P (sP), corticotropin-releasing hormone (CRH), and tumor necrosis factor-alpha (TNF alpha). Dexamethasone significantly reduced the volume and cellularity of the inflammatory exudates; in parallel, the levels of immunoreactive sP, CRH, and TNF alpha were significantly suppressed by this glucocorticoid. In contrast, immunoreactive Sms was stimulated by dexamethasone in a time-dependent fashion. These findings suggest another mechanism for suppression of the inflammatory reaction by glucocorticoids via stimulation of local Sms expression, which occurs in parallel to the inhibition of the local inflammatory mediators sP, CRH, and TNF alpha. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD USA. NIAMD, ARTHRIT & RHEUMATISM BRANCH, BETHESDA, MD 20892 USA. NR 45 TC 50 Z9 51 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1995 VL 136 IS 9 BP 4133 EP 4138 DI 10.1210/en.136.9.4133 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RQ622 UT WOS:A1995RQ62200056 PM 7544277 ER PT J AU ROGAN, WJ AF ROGAN, WJ TI ENVIRONMENTAL POISONING OF CHILDREN - LESSONS FROM THE PAST SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Symposium on Preventing Child Exposures to Environmental Hazards - Research and Policy Issues CY MAR 18-19, 1994 CL WASHINGTON, DC SP Childrens Environm Hlth Network, NIEHS, Univ Calif Berkeley, Sch Public Hlth Superfund Basic Res Program, Calif Dept Hlth Serv, W Alton Jones Fdn, Med Univ S Carolina, Environm Hazards Assessment Program, US EPA, Ctr Dis Control & Prevent, David and Lucile Packard Fdn, Calif Public Hlth Fdn, Impact Assessment Inc, March Dimes Birth Defects Fdn, Teratol Soc DE POLYCHLORINATED BIPHENYLS (PCBS); CHLORACNE; MOTHERS MILK; DICHLORODIPHENYL TRICHLOROETHANE (DDT); POLYBROMINATED BIPHENYLS (PBBS); HEXACHLOROBENZENE; ENDRIN; LEAD; MERCURY; ASBESTOS ID POLYCHLORINATED-BIPHENYLS; POLYBROMINATED BIPHENYLS; EXPOSURE; TAIWAN; PCBS AB Children have physiologic and behavioral characteristics that make them vulnerable to damage from environmental chemicals. In the past, there have been episodes in which children became ill or died from environmental exposures that spared adults or affected them less severely. Among the characteristics leading to children's sensitivity are their limited diets, dividing cells, differentiating organs and organ systems, slow or absent detoxification mechanisms, long life expectancy with the resulting ability to express damage with delayed consequences, and the severe metabolic demands of growth. There have been large outbreaks of poisonings involving children in Asia and Turkey, and some of the less obvious effects of chemicals have appeared in children in the United States. Although the United States has been spared a widespread outbreak of severe poisoning. such an incident is possible and would likely have greater consequences for children than adults. RP ROGAN, WJ (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 NR 29 TC 21 Z9 21 U1 1 U2 4 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 1995 VL 103 SU 6 BP 19 EP 23 DI 10.2307/3432339 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA TB481 UT WOS:A1995TB48100004 PM 8549472 ER PT J AU MILLER, RW AF MILLER, RW TI SPECIAL SUSCEPTIBILITY OF THE CHILD TO CERTAIN RADIATION-INDUCED CANCERS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Symposium on Preventing Child Exposures to Environmental Hazards - Research and Policy Issues CY MAR 18-19, 1994 CL WASHINGTON, DC SP Childrens Environm Hlth Network, NIEHS, Univ Calif Berkeley, Sch Public Hlth Superfund Basic Res Program, Calif Dept Hlth Serv, W Alton Jones Fdn, Med Univ S Carolina, Environm Hazards Assessment Program, US EPA, Ctr Dis Control & Prevent, David and Lucile Packard Fdn, Calif Public Hlth Fdn, Impact Assessment Inc, March Dimes Birth Defects Fdn, Teratol Soc DE RADIATION CARCINOGENESIS; PEDIATRICS; LEUKEMOGENESIS; BREAST CANCER; THYROID CANCER ID EXPOSURE AB The carcinogenic effects of exposure to ionizing radiation vary markedly with age, as revealed by studies of Japanese atomic bomb survivors and of Marshall Islanders exposed to fallout from U.S. nuclear weapons tests in the South Pacific in 1954. An increase in cancers of adulthood after intrauterine exposure, as reported in 1988, has not been sustained. After childhood exposure, increases in leukemia, breast cancer, and thyroid cancer are well established. The carcinogenic effects of radiation on the young have been reported after intrauterine exposures and after exposures during childhood. Cancers with short latent periods such as leukemia occur during childhood. but those with long latent periods such as breast cancer occur in adulthood. RP MILLER, RW (reprint author), NCI,CLIN EPIDEMIOL BRANCH,EPN-400,BETHESDA,MD 20892, USA. NR 13 TC 34 Z9 34 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 SEP PY 1995 VL 103 SU 6 BP 41 EP 44 DI 10.2307/3432343 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA TB481 UT WOS:A1995TB48100008 PM 8549487 ER PT J AU ZAHM, SH DEVESA, SS AF ZAHM, SH DEVESA, SS TI CHILDHOOD-CANCER - OVERVIEW OF INCIDENCE TRENDS AND ENVIRONMENTAL CARCINOGENS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Symposium on Preventing Child Exposures to Environmental Hazards - Research and Policy Issues CY MAR 18-19, 1994 CL WASHINGTON, DC SP Childrens Environm Hlth Network, NIEHS, Univ Calif Berkeley, Sch Public Hlth Superfund Basic Res Program, Calif Dept Hlth Serv, W Alton Jones Fdn, Med Univ S Carolina, Environm Hazards Assessment Program, US EPA, Ctr Dis Control & Prevent, David and Lucile Packard Fdn, Calif Public Hlth Fdn, Impact Assessment Inc, March Dimes Birth Defects Fdn, Teratol Soc DE CHILDREN; CANCER; RADIATION; ELECTROMAGNETIC FIELDS; MEDICATIONS; TOBACCO; PESTICIDES; WATER; LEUKEMIA; BRAIN TUMORS ID PATERNAL OCCUPATIONAL EXPOSURE; ACUTE NONLYMPHOCYTIC LEUKEMIA; FETAL HYDANTOIN SYNDROME; SOFT-TISSUE SARCOMAS; X-RAY-EXPOSURE; RISK-FACTORS; PARENTAL OCCUPATION; MAGNETIC-FIELDS; BRAIN-TUMORS; NUCLEAR-FACILITIES AB An estimated 8000 children 0 to 14 years of age are diagnosed annually with cancer in the United States. Leukemia and brain tumors are the most common childhood malignancies, accounting for 30 and 20% of newly diagnosed cases, respectively. From 1975 to 1978 to 1987 to 1990, cancer among white children increased slightly from 12.8 to 14.1/100,000. Increases are suggested for leukemia. gliomas, and, to a much lesser extent, Wilms' tumor. There are a few well-established environmental causes of childhood cancer such as radiation, chemotherapeutic agents, and diethylstilbestrol. Many other agents such as electromagnetic fields, pesticides. and some parental occupational exposures are suspected of playing roles. but the evidence is not conclusive at this time. Some childhood exposures such as secondhand cigarette smoke may contribute to cancers that develop many years after childhood. For some exposures such as radiation and pesticides data suggest that children may be more susceptible to the carcinogenic effects than similarly exposed adults. RP ZAHM, SH (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,6130 EXECUT BLVD,ROOM 418,ROCKVILLE,MD 20892, USA. RI Zahm, Shelia/B-5025-2015 NR 143 TC 56 Z9 59 U1 2 U2 5 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 SEP PY 1995 VL 103 SU 6 BP 177 EP 184 DI 10.2307/3432371 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA TB481 UT WOS:A1995TB48100036 PM 8549470 ER PT J AU BAIRD, DD MCCONNAUGHEY, DR WEINBERG, CR MUSEY, PI COLLINS, DC KESNER, JS KNECHT, EA WILCOX, AJ AF BAIRD, DD MCCONNAUGHEY, DR WEINBERG, CR MUSEY, PI COLLINS, DC KESNER, JS KNECHT, EA WILCOX, AJ TI APPLICATION OF A METHOD FOR ESTIMATING DAY OF OVULATION USING URINARY ESTROGEN AND PROGESTERONE METABOLITES SO EPIDEMIOLOGY LA English DT Note DE EPIDEMIOLOGIC METHODS; OVULATION; URINARY ESTRONE-3-GLUCURONIDE; URINARY PREGNANEDIOL-3-GLUCURONIDE; BIOMARKERS AB Longitudinal epidemiologic studies of menstrual and reproductive function are more informative if one can identify day of ovulation. We previously developed a method for estimating day of ovulation that is feasible for epidemiologic studies. The method relies on the relative concentrations of estrogen and progesterone metabolites in daily first-morning urine specimens and does not require creatinine adjustment. This paper describes results of applying this method to a large study with 724 menstrual cycles from 217 women. The method estimated a credible day of ovulation in 88% of cycles. Missing data accounted for most of the failures. When we excluded anovulatory cycles (1%) and cycles with missing data, the method estimated a day of ovulation in 97% of cycles. Variance in luteal phase length was small for our sample, suggesting that this method of identifying a day of ovulation introduces no more measurement error than when day of ovulation is determined by plasma luteinizing hormone (LH), the standard clinical method. RP BAIRD, DD (reprint author), NIEHS,EPIDEMIOL BRANCH,A3-05,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Wilcox, Allen/0000-0002-3376-1311; Baird, Donna/0000-0002-5544-2653 NR 0 TC 82 Z9 84 U1 0 U2 9 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 1995 VL 6 IS 5 BP 547 EP 550 DI 10.1097/00001648-199509000-00015 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RQ769 UT WOS:A1995RQ76900015 PM 8562634 ER PT J AU WILCOX, AJ AF WILCOX, AJ TI MOLECULAR EPIDEMIOLOGY - COLLISION OF 2 CULTURES SO EPIDEMIOLOGY LA English DT Editorial Material RP WILCOX, AJ (reprint author), NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709, USA. OI Wilcox, Allen/0000-0002-3376-1311 NR 0 TC 2 Z9 2 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 1995 VL 6 IS 5 BP 561 EP 562 DI 10.1097/00001648-199509000-00019 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RQ769 UT WOS:A1995RQ76900019 PM 8562638 ER PT J AU MONTPIED, P WINSKY, L DAILEY, JW JOBE, PC JACOBOWITZ, DM AF MONTPIED, P WINSKY, L DAILEY, JW JOBE, PC JACOBOWITZ, DM TI ALTERATION IN LEVELS OF EXPRESSION OF BRAIN CALBINDIN D-28K AND CALRETININ MESSENGER-RNA IN GENETICALLY EPILEPSY-PRONE RATS SO EPILEPSIA LA English DT Article DE HYBRIDIZATION IN SITU; CALCIUM-BINDING PROTEINS; CAUDATE AND ACCUMBENS NUCLEI; MESSENGER-RNA; REUNIENS NUCLEUS; SUBSTANTIA NIGRA COMPACTA ID CALCIUM-BINDING PROTEIN; FOCAL HIPPOCAMPAL EPILEPSY; RETICULAR THALAMIC NUCLEUS; SEIZURE PREDISPOSITION; AUDIOGENIC-SEIZURES; GENE-EXPRESSION; MESSENGER-RNA; IMMUNOHISTOCHEMICAL LOCALIZATION; INSITU HYBRIDIZATION; GENERALIZED EPILEPSY AB Variations in the concentration of free calcium in neurons is believed to play a major role in regulating neuronal excitability. Because calcium-binding proteins such as calbindin D-28k. and calretinin help to regulate intracellular calcium, we: investigated the possibility that the expression of these proteins may be affected in genetically epilepsy-prone rats (GEPRs). The mRNA levels of both proteins were compared across several brain regions using in situ hybridization histochemistry and Northern blot analysis with semiquantitation by optical density measures on autoradiograms from two GEPR strains that differ in the severity of audiogenic seizures (GEPR9 and GEPR3) and from Sprague-Dawfey rats. Results revealed a lower level of expression in calbindin D-28k mRNA in the caudate putamen-accumbens nuclei in GEPR3 (-30%) and GEPR9 (-60%) relative to controls, The calbindin D-28k mRNA level was also lower in the reuniens nucleus of the thalamus (-41% in GEPR3; - 34% in GEPR9). The calretinin mRNA level was lower in the substantia nigra compacta of both GEPR rat strains (-31% in GEPR3 and -34% in GEPR9 relative to controls). No changes in mRNA were detected in other brain regions expressing calbindin D-28k or calretinin mRNA. These results indicate that the expression of these related calcium-binding proteins is altered in the GEPRs before the induction of seizures. This initial defect could alter either the calcium-buffering capacity or regulation of calcium-mediated processes by these proteins and thus play a role in the molecular cascade of events inducing the genetic susceptibility to, and the generalization of, seizures in these rat strains. C1 NIMH, CLIN SCI LAB, BETHESDA, MD USA. UNIV ILLINOIS, COLL MED, PEORIA, IL USA. RP INSERM, U249, EXPTL MED LAB, CNRS, UPR 8402, F-34060 MONTPELLIER, FRANCE. NR 75 TC 12 Z9 12 U1 0 U2 1 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 EI 1528-1167 J9 EPILEPSIA JI Epilepsia PD SEP PY 1995 VL 36 IS 9 BP 911 EP 921 DI 10.1111/j.1528-1157.1995.tb01635.x PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA RQ059 UT WOS:A1995RQ05900009 PM 7649131 ER PT J AU BLAESE, M BLANKENSTEIN, T BRENNER, M COHENHAGUENAUER, O GANSBACHER, B SORRENTINO, B VELU, T AF BLAESE, M BLANKENSTEIN, T BRENNER, M COHENHAGUENAUER, O GANSBACHER, B SORRENTINO, B VELU, T TI EUROPEAN SCHOOL OF ONCOLOGY POSITION PAPER - GENE-THERAPY FOR THE MEDICAL ONCOLOGIST SO EUROPEAN JOURNAL OF CANCER LA English DT Article ID RESISTANT BONE-MARROW; MELANOMA-CELLS; TRANSPLANTATION; METHOTREXATE; PROTECTION; RECIPIENTS; MARKING C1 ST JUDE CHILDRENS RES HOSP, DIV BONE MARROW TRANSPLANTAT, MEMPHIS, TN 38101 USA. NIH, NATL CTR HUMAN GENOME RES, BETHESDA, MD 20892 USA. MAX DELBRUCK CENTRUM MOLEK MED, BERLIN, GERMANY. ST LOUIS HOSP, PARIS, FRANCE. MEM SLOAN KETTERING CANC CTR, NEW YORK, NY 10021 USA. HOP ERASME, BRUSSELS, BELGIUM. NR 26 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 1995 VL 31A IS 9 BP 1531 EP 1537 DI 10.1016/0959-8049(95)00295-T PG 7 WC Oncology SC Oncology GA RV456 UT WOS:A1995RV45600027 PM 7577084 ER PT J AU COLLEONI, M BIASIN, MR BONI, L NELLI, P MANENTE, P GAION, F PERASOLE, A INFANTOLINO, D AF COLLEONI, M BIASIN, MR BONI, L NELLI, P MANENTE, P GAION, F PERASOLE, A INFANTOLINO, D TI EVALUATION OF KI-67 EXPRESSION AS A PROGNOSTIC FEATURE IN HEPATOCELLULAR-CARCINOMA IN CIRRHOSIS SO EUROPEAN JOURNAL OF CANCER LA English DT Letter ID MULTIVARIATE-ANALYSIS C1 NATL CANC INST,DIV CLIN EPIDEMIOL,GENOA,ITALY. RP COLLEONI, M (reprint author), CITY HOSP,MED ONCOL SERV,VIA OSPED 1,I-31033 CASTELFRANCO VENE,ITALY. NR 10 TC 5 Z9 5 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 1995 VL 31A IS 9 BP 1547 EP 1548 DI 10.1016/0959-8049(95)00239-F PG 2 WC Oncology SC Oncology GA RV456 UT WOS:A1995RV45600031 PM 7577088 ER PT J AU BARTENS, W RADER, DJ TALLEY, G BREWER, HB AF BARTENS, W RADER, DJ TALLEY, G BREWER, HB TI LIPOPROTEIN (A) IN PATIENTS WITH HYPERLIPIDEMIA SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE APOPROTEIN(A); ATHEROSCLEROSIS; HYPERLIPIDEMIA ID LP(A) GLYCOPROTEIN PHENOTYPES; B-CONTAINING LIPOPROTEINS; CORONARY HEART-DISEASE; APOLIPOPROTEIN-B; PLASMA LIPOPROTEIN(A); NEPHROTIC SYNDROME; DENSITY; GENE; ATHEROSCLEROSIS; ASSOCIATION AB Lipoprotein (a) [Lp(a)] is an atherogenic lipoprotein which is similar in structure to, but metabolically distinct from, LDL. Factors modulating plasma Lp(a) concentrations are poorly understood. We hypothesized that patients with hyperlipidaemia have elevated Lp(a) levels and determined the phenotype, concentration and distribution of Lp(a) in a group of hyperlipidaemic patients (n = 107) compared with a control group (n = 128). Lp(a) concentrations were significantly increased in the hyperlipidaemic patients (mean, 34 +/- 4 mg dL(-1). median, 19 mg dL(-1)) compared with the controls (20 +/- 3 mg dL(-1)); 9 mg dL(-1))) (P < 0.01). Interestingly, after dividing the patients into one group with elevated cholesterol (> 200 mg dL(-1)) (n = 44) and another group with elevated triglycerides (> 200 mg dL(-1)) (n = 51) we found that Lp(a) concentrations were 2.3-fold higher in the high cholesterol patients (mean, 45 +/- 5; median, 41 mg dL(-1)) compared to the high triglyceride subjects (20 +/- 4; 8 mg dL(-1)) (P < 0.01). Furthermore, a negative correlation between triglyceride and Lp(a) plasma concentrations was found in patients exhibiting triglyceride levels > 300 mg dL(-1) (r= -0.41, P = 0.04, n = 36) and with triglycerides > 400 mg dL(-1) (r= -0.52, P = 0.03, n = 17). These data indicate that plasma Lp(a) concentrations are elevated in hyperlipidaemia if the patients have high cholesterol levels, whereas Lp(a) is normal to low in patients with elevated triglycerides. The dominating lipid elevation in this condition and increased Lp(a) levels may contribute to the increased risk of premature coronary artery disease (CAD) in hyperlipidaemic patients. C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. NR 38 TC 15 Z9 17 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD SEP PY 1995 VL 25 IS 9 BP 647 EP 653 DI 10.1111/j.1365-2362.1995.tb01980.x PG 7 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA RV302 UT WOS:A1995RV30200003 PM 7498237 ER PT J AU ABRAMS, SI DOBRZANSKI, MJ WELLS, DT STANZIALE, SE ZAREMBA, S MASUELLE, L KANTOR, JA SCHLOM, J AF ABRAMS, SI DOBRZANSKI, MJ WELLS, DT STANZIALE, SE ZAREMBA, S MASUELLE, L KANTOR, JA SCHLOM, J TI PEPTIDE-SPECIFIC ACTIVATION OF CYTOLYTIC CD4(+) T-LYMPHOCYTES AGAINST TUMOR-CELLS BEARING MUTATED EPITOPES OF K-RAS P21 SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE T(H)1 CELLS; MUTATED RAS P21; PEPTIDES; CYTOTOXICITY; IMMUNOTHERAPY ID CLASS-II MOLECULES; FUNCTIONAL-PROPERTIES; LYMPHOKINE SECRETION; ANTIGEN EXPRESSION; INTERFERON-GAMMA; GENE-TRANSFER; IA-ANTIGENS; TH1 CLONES; A-BETA; LINES AB Alterations in the ms p21 protein have been associated with both rodent and human neoplasia. Thus, mutated I ds p21 proteins may bear unique antigenic epitopes for immune recognition, such as by T cells, which have been implicated in host antitumor activity. Synthetic peptides that mimic segments of mutated ras p21 have been reported to be immunogenic in mice in vivo, although detailed functional analyses remains undefined. Here, in a murine model, we explored and characterized distinct effector properties of host-derived T lymphocytes reactive to mutated ras peptides, which was consistent with the CD4(+) T helper type 1 (T(h)1) subset. BALB/c mice (H-2(d)) were immunized with a purified peptide, 13 amino acids in length, containing the substitution of Gly (G12) to Val (V12) at position 12, which is commonly found in human carcinomas. An alpha beta T cell receptor-positive, CD3(+), CD4(+), CD8(-) T cell line was established, which expressed peptide-specific proliferation. Cytokine assays revealed the production of interleukin-2, interferon-gamma, tumor necrosis factor and granulocyte-macrophage colony-stimulating factor. Moreover, antigen-specific cytotoxicity was demonstrable against: (1) Ia(d)-bearing A20 tumor cells incubated with exogenously bound V12 peptide; and (2) A20 tumor cells transduced with the K-vas p21 oncogene encoding the corresponding point mutation. CD4(+)-mediated cytotoxicity was major histocompatibility complex (MHC) class II-restricted, as revealed by the absence of lysis against MHC class II- P815 targets, inhibition of A20 lysis with anti-Ia(d) monoclonal antibodies, and induction of lysis against L cell targets transfected with E alpha A beta(d). Independent isolation of a second CD4(+) V12 line revealed a very similar cytolytic and MHC class II-restricted profile. Overall, these data demonstrated that peptide immunization produced a CD4(+) T(h)1 response that specifically recognized tumor cells expressing endogenous activated K-ras epitopes, which may have implications for the development of peptide-based active immunotherapies. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NIH,HOWARD HUGHES MED INST,RES SCHOLAR PROGRAM,BETHESDA,MD. NR 57 TC 39 Z9 39 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 SEP PY 1995 VL 25 IS 9 BP 2588 EP 2597 DI 10.1002/eji.1830250928 PG 10 WC Immunology SC Immunology GA RX342 UT WOS:A1995RX34200027 PM 7589131 ER PT J AU XU, LL MCVICAR, DW BENBARUCH, A KUHNS, DB JOHNSTON, J OPPENHEIM, JJ WANG, JM AF XU, LL MCVICAR, DW BENBARUCH, A KUHNS, DB JOHNSTON, J OPPENHEIM, JJ WANG, JM TI MONOCYTE CHEMOTACTIC PROTEIN-3 (MCP3) INTERACTS WITH MULTIPLE LEUKOCYTE RECEPTORS - BINDING AND SIGNALING OF MCP3 THROUGH SHARED AS WELL AS UNIQUE RECEPTORS ON MONOCYTES AND NEUTROPHILS SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE MCP3; C-C CHEMOKINES; RECEPTOR ID HUMAN INTERLEUKIN-8 RECEPTOR; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; CYTOKINE FAMILY; CELLS; IDENTIFICATION; CHEMOKINES; BIOLOGY; CDNA AB The diversity of monocyte chemotactic protein (MCP)3 target cell types, as well as the capacity of MCP3 to desensitize leukocyte responses to other CC chemokines, suggested that MCP3 may interact with multiple CC chemokine receptors. The purpose of this study is to establish how MCP3 binds and activates monocytes and neutrophils. We show that human monocytes exhibit high-affinity binding for I-125-MCP3 with an estimated Kd of 1-3 nM and about 10 000 binding sites/cell. The binding of I-125-MCP3 to monocytes was progressively less well competed by CC chemokines macrophage inflammatory protein (MIP)1 alpha (Kd = 5-10 nM), RANTES (Kd = 5-10 nM), MCP1 (monocyte chemoattractant and activating factor, or MCAF) (Kd = 60 nM) and MIP1 beta (Kd > 100 nM). On the other hand, unlabeled MCP3 displaced the binding of radiolabeled MIP1 alpha, RANTES, MCP1 and MIP1 beta as effectively as the isologous CC chemokines. In agreement with the binding data, pretreatment of monocytes with MCP3 completely desensitized the calcium flux in response to MIP1 alpha and RANTES. However, MIP1 alpha and RANTES failed to desensitize the response of monocytes to MCP3. MCP3 and MCP1 partially desensitized each other's effects on monocytes. These binding and cross-desensitization results suggest that MCP3 binds and signals through other binding sites in addition to those shared with MIP1 alpha, RANTES and MCP1, The unidirectional competition for MIP1 beta binding and signaling by MCP3 suggests the existence of an as-yet unidentified site for MCP3 shared with MIP1 beta. The existence of another unique binding site(s) for MCP3 was further shown by the failure of any of the other CC chemokines to compete effectively for MCP3 binding on neutrophils. MCP3 in our study was also the only human CC chemokine that consistently chemoattracted neutrophils. These results suggest that MCP3 is a ligand that can bind and activate a broad range of target cells through receptors shared by other CC chemokines as well as its own receptor. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SAIC,CLIN IMMUNOL SERV,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702. RI McVicar, Daniel/G-1970-2015 NR 33 TC 61 Z9 62 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 SEP PY 1995 VL 25 IS 9 BP 2612 EP 2617 DI 10.1002/eji.1830250931 PG 6 WC Immunology SC Immunology GA RX342 UT WOS:A1995RX34200030 PM 7589134 ER PT J AU LI, J WIRTZ, RA MCCONKEY, GA SATTABONGKOT, J WATERS, AP ROGERS, MJ MCCUTCHAN, TF AF LI, J WIRTZ, RA MCCONKEY, GA SATTABONGKOT, J WATERS, AP ROGERS, MJ MCCUTCHAN, TF TI PLASMODIUM - GENUS-CONSERVED PRIMERS FOR SPECIES IDENTIFICATION AND QUANTITATION SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE MALARIA; PLASMODIUM FALCIPARUM; PLASMODIUM GALLINACEUM; PLASMODIUM KNOWLESI; PLASMODIUM MALARIAE; PLASMODIUM OVALE; PLASMODIUM VIVAX; SSU RIBOSOMAL-RNA; 18S RIBOSOMAL-RNA; COMPETITIVE RT/PCR; DIAGNOSTICS ID SUBUNIT RNA SEQUENCES; RIBOSOMAL-RNA; FALCIPARUM; MALARIA; GENES; COMPILATION; DIAGNOSIS; BERGHEI AB Stable RNAs have regions of primary sequence that are nearly identical in every member of the Plasmodium genus and not found in the host or in other common pathogens. Several ''genus-conserved'' sequences, which flank hypervariable regions, were identified within the small subunit ribosomal RNA of Plasmodium species. Primers based on these conserved sequences permit amplification of species- or possibly even strain-specific sequences from samples of unknown composition. As an example of this approach, sequences from the four human malaria species were successfully recovered from Giemsa-stained blood smears, including two different sequences for Plasmodium ovale (of 91.5% similarity). This type of information is useful for epidemiological and phylogenetic analysis of any malaria species. We show that amplification of rRNA-derived sequences behaves in a competitive fashion during the cycles of polymerase amplification and therefore target sequences from Plasmodium species are amplified in proportion to their abundance in the sample. There are several implications of this finding. (1) The proportion of different products resulting from amplification from samples with mixed infections is closely related to the proportion of infecting species, (2) Direct quantitation of parasite nucleic acids within a sample can be derived when known amounts of competitor RNA are added to the RT/PCR reaction. (3) Amplification of rRNA sequences, using genus-specific primers, allows one to monitor the development of the parasite in the mosquito. (C) 1995 Academic Press, Inc. C1 WALTER REED ARMY MED CTR,DEPT ENTOMOL,DIV COMMUNICABLE DIS & IMMUNOL,WASHINGTON,DC 20307. NIAID,PARASIT DIS LAB,GROWTH & DEV SECT,BETHESDA,MD 20892. LEIDEN UNIV,PARASITOL LAB,LEIDEN,NETHERLANDS. USA,MED COMPONENT,DEPT ENTOMOL,BANGKOK,THAILAND. RP LI, J (reprint author), UNIFORMED SERV UNIV HLTH SCI,DEPT PREVENT MED & BIOMETR,4301 JONES BRIDGE RD,BETHESDA,MD 20814, USA. RI Waters, Andy/C-9377-2009 OI Waters, Andy/0000-0001-8900-2982 NR 21 TC 77 Z9 82 U1 1 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD SEP PY 1995 VL 81 IS 2 BP 182 EP 190 DI 10.1006/expr.1995.1107 PG 9 WC Parasitology SC Parasitology GA RV904 UT WOS:A1995RV90400005 PM 7556560 ER PT J AU BATISTA, MC CARTLEDGE, TP ZELLMER, AW MERINO, MJ AXIOTIS, C BREMNER, WJ NIEMAN, LK AF BATISTA, MC CARTLEDGE, TP ZELLMER, AW MERINO, MJ AXIOTIS, C BREMNER, WJ NIEMAN, LK TI EFFECTS OF AGING ON MENSTRUAL-CYCLE HORMONES AND ENDOMETRIAL MATURATION SO FERTILITY AND STERILITY LA English DT Article DE LUTEINIZING HORMONE; FOLLICLE-STIMULATING HORMONE; ESTRADIOL; PROGESTERONE; INHIBIN; PLACENTAL PROTEIN 14; ENDOMETRIAL BIOPSY ID INHIBIN LEVELS; IMMUNOREACTIVE INHIBIN; MENOPAUSAL TRANSITION; INVITRO FERTILIZATION; LUTEINIZING-HORMONE; OLDER WOMEN; AGE; PROGESTERONE; ESTRADIOL; OVARIAN AB Objective: To investigate changes in menstrual cycle hormones and endometrial maturation that may contribute to the decline in fertility with aging. Design: Prospective controlled clinical study. Setting: Normal human volunteers in an academic research institution. Subjects: Women with regular menstrual cycles. Interventions: Thirty-two women, aged 20 to 30 or 40 to 50 years, had daily blood drawing starting on cycle day 6 to 10 and continuing until 2 days after the onset of next menses. In addition, 60 women, aged 20 to 30 or 40 to 50 years, had a total of 93 endometrial biopsies performed on day 7 to 9 after the LH surge. Main Outcome Measures: Serum LH, FSH, E(2), inhibin, P, and placental protein 14 (PP14) levels and histologic maturation of the endometrium. Results: Serum FSH levels were increased whereas inhibin concentrations were reduced in the luteal-follicular transition of women >40 years. No other hormonal changes were seen in this population, including P and PP14 secretion. Disruption of endometrial maturation occurred at a similar frequency in both age groups. Conclusions: Follicular recruitment, but not luteal function or endometrial maturation, is disturbed in cycling women >40 years and may contribute to the decline in fertility with aging. C1 NICHHD,WARREN GRANT MAGNUSON CLIN CTR,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. UNIV WASHINGTON,VET AFFAIRS MED CTR,SEATTLE,WA 98195. NR 25 TC 23 Z9 24 U1 0 U2 1 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 SEP PY 1995 VL 64 IS 3 BP 492 EP 499 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA RQ860 UT WOS:A1995RQ86000006 PM 7641900 ER PT J AU BURIN, GJ CLAYSON, DB COHEN, SM DESESSO, JM ELLWEIN, LB FISHBEIN, L FREDERICK, C GIBB, H GORELICK, NJ HARD, GC HILL, RN KING, C LORENTZEN, RJ OYASU, R RICE, JM SANDUSKY, C WANG, CY WARD, JM AF BURIN, GJ CLAYSON, DB COHEN, SM DESESSO, JM ELLWEIN, LB FISHBEIN, L FREDERICK, C GIBB, H GORELICK, NJ HARD, GC HILL, RN KING, C LORENTZEN, RJ OYASU, R RICE, JM SANDUSKY, C WANG, CY WARD, JM TI URINARY-BLADDER CARCINOGENESIS - IMPLICATIONS FOR RISK ASSESSMENT SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article ID CELL-PROLIFERATION; RATS; MELAMINE; MICE C1 UNIV NEBRASKA,MED CTR,DEPT PATHOL & MICROBIOL,LINCOLN,NE 68583. MITRE CORP,MCLEAN,VA 22101. NEI,BETHESDA,MD 20892. PRINCETON SCI PUBLISHING CO,PRINCETON,NJ. ROHM & HAAS CO,PHILADELPHIA,PA 19105. US EPA,OFF HLTH & ENVIRONM ASSESSMENT,WASHINGTON,DC 20460. AMER HLTH FDN,NEW YORK,NY 10017. US EPA,OFF PREVENT PESTICIDES & TOX SUBST,WASHINGTON,DC 20460. MICHIGAN CANC FDN,DETROIT,MI 48201. US FDA,ROCKVILLE,MD 20857. NORTHWESTERN UNIV,SCH MED,DEPT PATHOL,EVANSTON,IL 60208. RP BURIN, GJ (reprint author), TECHNOL SCI GRP INC,WASHINGTON,DC, USA. NR 32 TC 15 Z9 16 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD SEP PY 1995 VL 33 IS 9 BP 797 EP 802 PG 6 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA RY163 UT WOS:A1995RY16300010 ER PT J AU DONZANTI, BA KELLEY, JA TOMASZEWSKI, JE ROTH, JS TOSCA, P PLACKE, M SINGER, A YARRINGTON, JT DRISCOLL, JS AF DONZANTI, BA KELLEY, JA TOMASZEWSKI, JE ROTH, JS TOSCA, P PLACKE, M SINGER, A YARRINGTON, JT DRISCOLL, JS TI ACUTE CARDIOTOXICITY OF THE ANTI-HIV DIDEOXYNUCLEOSIDE, F-DDA, IN THE RAT SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID PHARMACOKINETICS; 2',3'-DIDEOXYADENOSINE; 2',3'-DIDEOXYINOSINE; INFECTION AB 2'-beta-Fluoro-2',3'-dideoxyadenosine (F-ddA), an acid-stable, purine dideoxynucleoside with in vitro anti-HIV activity, has been selected by the NCI as a clinical trial candidate. A recent report that high, single doses of F-ddA produce cardiotoxicity in rats prompted the present investigation whose objective was to quantitate this effect and establish a relationship between this toxicity and F-ddA plasma concentrations. Microscopic examination of cardiac tissues for degenerative lesions established the effects of F-ddA and ddA on three iv schedules [daily x 1 (2.5-250 mg/kg); daily x 5 (125, 250 mg/kg), and BID x 1 (250 mg/kg)] as well as one oral schedule [BID x 1 (500 mg/kg)] using 8- to 12-week-old female Sprague-Dawley rats. For both F-ddA and ddA, the group mean severity of the cardiac lesions was dose-dependent and proportional to the measured plasma concentrations of the undeaminated parent drugs. F-ddI and ddI, the respective deaminated catabolites of F-ddA and ddA, were essentially nontoxic in this study (iv, 250 mg/kg, daily x 1 and daily x 5), since plasma concentrations exceeding 2 mM produced only minimal cardiac lesions. The cardiomyopathy of F-ddA was minimal to mild for all iv doses except 250 mg/kg (daily x 1) and usually was greater than that of ddA at any given dose. This is a consequence of the fact that F-ddA is deaminated 20 times more slowly than ddA, resulting in higher plasma concentrations of F-ddA relative to ddA at any given time for any given dose. Neither F-ddA nor ddA was more cardiotoxic on a repeated iv schedule (daily x 5) than when administered only once, suggesting that rat cardiotoxicity is related to C-max rather than total exposure. In this most sensitive species, the formation of cardiac lesions above the background level is associated with iv F-ddA administration when the F-ddA plasma concentration approaches 300 mu M, 30-50 times the anticipated therapeutic level in humans. (C) 1995 Society of Toxicology C1 NCI,MED CHEM LAB,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,TOXICOL BRANCH,BETHESDA,MD 20892. BATTELLE MEM INST,COLUMBUS,OH 43201. FU NCI NIH HHS [N01-CM-97617, N01-CM-37834] NR 22 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD SEP PY 1995 VL 27 IS 2 BP 167 EP 176 DI 10.1006/faat.1995.1121 PG 10 WC Toxicology SC Toxicology GA RU766 UT WOS:A1995RU76600002 PM 8529811 ER PT J AU RATAJCZAK, HV THOMAS, PT HOUSE, RV GAWORSKI, CL SHERWOOD, RL LUSTER, MI HAGEN, KL ABDO, K JACKSON, CD ROYCROFT, J ARANYI, C AF RATAJCZAK, HV THOMAS, PT HOUSE, RV GAWORSKI, CL SHERWOOD, RL LUSTER, MI HAGEN, KL ABDO, K JACKSON, CD ROYCROFT, J ARANYI, C TI LOCAL VERSUS SYSTEMIC IMMUNOTOXICITY OF ISOBUTYL NITRITE FOLLOWING SUBCHRONIC INHALATION EXPOSURE OF FEMALE B6C3F1 MICE SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID AMYL NITRITE; HOST-RESISTANCE; HOMOSEXUAL MEN; TOXICITY; IMMUNITY; SARCOMA AB Female B6C3F1 mice were exposed to isobutyl nitrite (IBN) by inhalation at 0, 37.5, 75, or 150 ppm for 6 hr per day, 5 days per week for 15 weeks. The potential of this compound to induce immunotoxicity was assessed during the 3rd, 13th, 14th, and 15th week of exposure and after 2 weeks of recovery following the 15 weeks of exposure. Both systemic and lung immune functions were examined, including body and lymphoid organ weights, pulmonary macrophage function and host defense, expression of splenic lymphocyte cell-surface markers, natural killer cell function, mixed lymphocyte reaction, and induction of specific antibody to a T-cell-dependent antigen. There was a dose-related suppression of T-cell-dependent antibody-forming cell responses in the spleen following IBN exposure; however, other measures of T-cell and nonspecific immunity were not significantly affected. A dose-related increase of H2O2 production by alveolar macrophages was present after 12 but not after 68 exposures to IBN. In contrast, pulmonary host defense mechanisms against Klebsiella pneumoniae were unaffected. These results suggest that in the absence of changes in host resistance, IBN may have selective and partially reversible effects on the immune system. (C) 1995 society of Toxicology C1 NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. UNIV ILLINOIS,HLTH SCI CTR,CTR RES RESOURCES,CHICAGO,IL 60612. NATL CTR TOXICOL RES,JEFFERSON,AR 72079. RP RATAJCZAK, HV (reprint author), IIT,RES INST,DEPT LIFE SCI,10 W 35TH ST,CHICAGO,IL 60616, USA. FU NIEHS NIH HHS [N01-ES-65143] NR 25 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD SEP PY 1995 VL 27 IS 2 BP 177 EP 184 DI 10.1006/faat.1995.1122 PG 8 WC Toxicology SC Toxicology GA RU766 UT WOS:A1995RU76600003 PM 8529812 ER PT J AU MORGAN, DL MAHLER, JF MOORMAN, MP WILSON, RE PRICE, HC RICHARDS, JH OCONNOR, RW AF MORGAN, DL MAHLER, JF MOORMAN, MP WILSON, RE PRICE, HC RICHARDS, JH OCONNOR, RW TI COMPARISON OF STYRENE HEPATOTOXICITY IN B6C3F1 AND SWISS MICE SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID INHALATION TOXICITY; STYRENE-7,8-OXIDE; SUSCEPTIBILITY AB Inhalation exposure to styrene at concentrations that cause metabolic saturation results in significantly greater hepatotoxicity in B6C3F1 mice than in Swiss mice; females of both strains are more susceptible than males. These studies were conducted to investigate the mouse strain and gender differences in susceptibility to hepatotoxicity caused by repeated exposure to styrene at concentrations that do not cause metabolic saturation. Male and female B6C3F1 and Swiss mice (8 weeks old) were exposed to 0, 150, or 200 ppm styrene for 6 hr/day, 5 days/week, for up to 2 weeks. Changes in body and liver weights, serum alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH) levels, liver histopathology, and total liver glutathione (GSH) were evaluated after 2, 3, 5, and 10 exposures (six mice/sex/strain/time point/concentration). Blood levels of styrene and styrene-7,8-oxide (SO) were measured in mice exposed to 200 ppm styrene for 2, 3, or 5 days (six mice/sex/strain/time point/concentration). Serum ALT and SDH levels were significantly elevated only in female B6C3F1 mice after 3 exposures to 200 ppm styrene; enzyme levels had returned to control levels when measured after 5 and 10 exposures. Degeneration and coagulative necrosis of centrilobular hepatocytes were observed in female B6C3F1 mice exposed 2, 3, and 5 days to 150 or 200 ppm styrene; incidences of these lesions were greater in the 200 ppm than in the 150 ppm dose group. After 10 days of exposure to 150 or 200 ppm styrene, hepatocellular lesions had resolved, although a residual chronic inflammation was present in livers of most female B6C3F1 mice. Degeneration of centrilobular hepatocytes was observed in one male B6C3F1 mouse after 3 exposures to 200 ppm, and no significant lesions were observed in livers of exposed Swiss mice. Significant dose-related decreases in hepatic GSH were observed in both sexes of both strains throughout the 2-week exposure. In general, hepatic GSH depletion was greatest in female B6C3F1 mice. Exposure to 200 ppm caused 60-70% GSH depletion in female B6C3F1 mice at each time point. GSH depletion generally decreased in B6C3F1 mice and increased in Swiss mice with continued exposure to 150 ppm styrene. With continued exposure to 200 ppm, GSH depletion generally decreased in all mice. Blood styrene and SO levels increased in all groups with the number of exposures. Styrene levels were significantly higher in B6C3F1 mice than in Swiss mice; however, within each strain gender differences were not significant. These data suggest that the transient hepatotoxicity in female B6C3F1 mice was related to greater hepatic GSH depletion and/or slower GSH regeneration in these animals. (C) 1995 Society of Toxicology C1 MANTECH ENVIRONM TECHNOL INC,RES TRIANGLE PK,NC 27709. RP MORGAN, DL (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 9 TC 12 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD SEP PY 1995 VL 27 IS 2 BP 217 EP 222 DI 10.1006/faat.1995.1126 PG 6 WC Toxicology SC Toxicology GA RU766 UT WOS:A1995RU76600007 PM 8529816 ER PT J AU MARSMAN, DS GRUMBEIN, SL HASEMAN, JK HAILEY, JR AF MARSMAN, DS GRUMBEIN, SL HASEMAN, JK HAILEY, JR TI CHRONIC NEPHROPATHY AND RENAL CARCINOGENICITY OF O-BENZYL-P-CHLOROPHENOL IN F344/N RATS AND B6C3F(1) MICE SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID ZERO DOSE CONTROL; CELL-PROLIFERATION; STATISTICAL ISSUES; TESTS; DETERGENT AB o-Benzyl-p-chlorophenol, an aryl halide biocide, was evaluated in male and female F344/N rats and B6C3F(1) mice in a series of subchronic and 2-year toxicity and carcinogenicity studies. Kidney was the primary target of toxicity in the 13-week gavage studies in rats and mice, with increased nephropathy noted as low as 240 mg/kg in male rats. Considering the nephropathy to be dose-limiting, the chronic (2-year) study was conducted at lower doses (male rats: 30, 60, or 120 mg/kg; female rats: 60, 120, or 240 mg/ kg; male and female mice: 120, 240, or 480 mg/kg; in corn oil; n = 50/group). Survival and body weights of dosed fats were similar to controls in the 2-year study. Survival of high-dose male and female mice, and body weights of all dosed male and mid- and high-dose female mice, were lower than controls. The incidence and severity of nephropathy increased with dose and length of treatment in both rats and mice. There was an increased incidence of renal tubule adenomas or carcinomas in both the mid- and high-dose male mice. Despite similar evidence of nephropathy, however, there were no increased incidences of neoplasms in female mice or in male or female rats. This study suggests therefore that while nephrotoxicity may have been a necessary component, factors other than the marked nephrotoxicity of o-benzyl-p-chlorophenol were critical to the development of renal carcinogenesis induced in only male mice. (C) 1995 Society of Toxicology C1 NIEHS,RES TRIANGLE PK,NC 27709. BATTELLE MEM INST,COLUMBUS LABS,COLUMBUS,OH 43201. NR 44 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD SEP PY 1995 VL 27 IS 2 BP 252 EP 262 DI 10.1006/faat.1995.1131 PG 11 WC Toxicology SC Toxicology GA RU766 UT WOS:A1995RU76600012 PM 8529821 ER PT J AU SANDERS, VM ELWELL, MR HEATH, JE COLLINS, BJ DUNNICK, JK RAO, GN PREJEAN, D LINDAMOOD, C IRWIN, RD AF SANDERS, VM ELWELL, MR HEATH, JE COLLINS, BJ DUNNICK, JK RAO, GN PREJEAN, D LINDAMOOD, C IRWIN, RD TI INDUCTION OF THYMIC LYMPHOMA IN MICE ADMINISTERED THE DIDEOXYNUCLEOSIDE DDC SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID AIDS-RELATED COMPLEX; NUCLEOSIDE ANALOGS; III INFECTIVITY; SINGLE AGENTS; 2',3'-DIDEOXYCYTIDINE; TOXICITY; CELLS; PHARMACOKINETICS; DIDEOXYCYTIDINE; COMBINATION AB Groups of 10 male and 20 female B6C3F1 mice received 0, 500, or 1000 mg/kg/day 2',3'-dideoxycytidine (ddC) by gavage for 13 weeks. At the end of the 13-week exposure period all males and 10 females per group were necropsied while the remaining females were held for 1 month without further treatment. Thymic atrophy was present at the 13-week necropsy in male and female mice administered 1000 mg/kg/day and in females administered 500 mg/kg/day, but was not present in females following 1 month of recovery. Thymic lymphoma was present in 1 female that received 500 mg/kg/day and 1 female that received 1000 mg/kg/day. In a follow-up study groups of 70 female mice received 0, 500, or 1000 mg/kg/day for 13 weeks. At the end of the 13-week exposure period 20 mice per group were necropsied and the remaining animals held for 3 months without further treatment. Thymic atrophy was observed in ddC-exposed groups at the 13-week necropsy but not in mice allowed to recover for 13 weeks. Thymic lymphoma occurred in 3/50 mice that received 500 mg/kg/day and in 17/50 mice that received 1000 mg/kg/day but did not occur in mice from the vehicle control group. (C) 1995 Society of Toxicology C1 NIEHS,NATL TOXICOL PROGRAM,ENVIRONM TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. SO RES INST,BIRMINGHAM,AL 35255. NR 28 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD SEP PY 1995 VL 27 IS 2 BP 263 EP 269 DI 10.1006/faat.1995.1132 PG 7 WC Toxicology SC Toxicology GA RU766 UT WOS:A1995RU76600013 PM 8529822 ER PT J AU EGLITIS, MA SCHNEIDERMAN, RD RICE, PM EIDEN, MV AF EGLITIS, MA SCHNEIDERMAN, RD RICE, PM EIDEN, MV TI EVALUATION OF RETROVIRAL VECTORS BASED ON THE GIBBON APE LEUKEMIA-VIRUS SO GENE THERAPY LA English DT Article DE RETROVIRUSES; GENE TRANSFER; GENETIC VECTORS; GIBBON APE LEUKEMIA VIRUS ID NUCLEOTIDE-SEQUENCE; TERMINAL REPEAT; SARCOMA-VIRUS; HOST-RANGE; MURINE; CELLS; INFECTION; ENHANCER AB The gibbon ape leukemia viruses (GaLVs) are primate-derived C-type retroviruses with a broad host range. Using an infectious, full-length clone of the GaLV SEATO strain, we have determined that this virus replicates efficiently in 13 of 17 human cell lines tested. In fact, the SB lymphoblast cell line, while resistant to infection by wild-type amphotropic mouse leukemia virus (A-MLV), was infected by GaLV-SEATO. We constructed vectors containing GaLV components and compared the performance of genomes containing an enhancer and promoter derived either from the SEATO or SF strains of GaLV. The GaLV vector genomes were packaged in a Moloney (Mo)MLV core with either an A-MLV or GaLV SEATO envelope. We found that, in some cases, the vector genome appeared to be critical in obtaining optimal infection. For example, vectors with a GaLV SF-based genome infected the human HL60 cell line, whereas vectors with a GaLV SEATO-based genome did not We also found that most, but not all, of the human cell lines tested were more susceptible to vectors packaged with the GaLV SEATO than A-MLV envelope. The source of the viral core was also important, in that some human cells appeared susceptible to infection only with GaLV genomes packaged in particles composed of a GaLV core and envelope. Our results show that GaLV-based packageable genomes can be expressed in target cells not efficiently infected by vectors containing MoMLV-based genomes. These results suggest that judicious combinations of retroviral genomes and structural components can significantly improve gene transfer into human cells. C1 NIMH,CELL BIOL LAB,MOLEC VIROL UNIT,BETHESDA,MD 20892. NR 26 TC 13 Z9 13 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0969-7128 J9 GENE THER JI Gene Ther. PD SEP PY 1995 VL 2 IS 7 BP 486 EP 492 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA RT118 UT WOS:A1995RT11800008 PM 7584127 ER PT J AU SADOFSKY, MJ HESSE, JE VANGENT, DC GELLERT, M AF SADOFSKY, MJ HESSE, JE VANGENT, DC GELLERT, M TI RAG-1 MUTATIONS THAT AFFECT THE TARGET SPECIFICITY OF V(D)J RECOMBINATION - A POSSIBLE DIRECT ROLE OF RAG-1 IN SITE RECOGNITION SO GENES & DEVELOPMENT LA English DT Article DE V(D)J RECOMBINATION; RAG-1; MUTAGENESIS; PLASMID LIBRARY ID JOINING SIGNALS; SEQUENCE; GENES; MICE AB The RAG-1 protein plays an essential role in V(D)J recombination, but its exact function has not yet been defined. Here we report that a particular mutation in RAG-1 affects recombination by altering the specificity of target sequence usage. Recombination mediated by wild-type RAG-1 is tolerant of a wide range of coding sequences adjacent to the recombination signal. With the mutant RAG-1, recombination is much more demanding; efficient recombination is only found when particular dinucleotides are adjacent to the signal sequence heptamer. The mutant is also more sensitive than wild-type RAG-1 to certain alterations within the signal sequence. We suggest that the RAG-1 protein may interact physically with the target DNA at the coding-signal sequence border. RP SADOFSKY, MJ (reprint author), NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 15 TC 61 Z9 61 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD SEP 1 PY 1995 VL 9 IS 17 BP 2193 EP 2199 DI 10.1101/gad.9.17.2193 PG 7 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA RU602 UT WOS:A1995RU60200010 PM 7657170 ER PT J AU DINMAN, JD WICKNER, RB AF DINMAN, JD WICKNER, RB TI 5S-RIBOSOMAL-RNA IS INVOLVED IN FIDELITY OF TRANSLATIONAL READING FRAME SO GENETICS LA English DT Article ID RIBOSOMAL FRAMESHIFTING SIGNAL; STRANDED-RNA VIRUS; YEAST SACCHAROMYCES-CEREVISIAE; HIGHER-ORDER STRUCTURE; POL FUSION PROTEIN; DNA GENES; NUCLEOTIDE-SEQUENCE; MUTATIONAL ANALYSIS; SHUTTLE VECTORS; CHROMOSOME-XII AB Chromosomal mutants (maintenance of frame = mof) in which the efficiency of -1 ribosomal frameshifting is increased can be isolated using constructs in which lacZ expression is dependent upon a -1 shift of reading frame. We isolate a new mof mutation, mof9, in Saccharomyces cerevisiae and show that it is complemented by both single and multi-copy 5 S rDNA clones. Two independent insertion mutations in the rDNA. locus (rDNA::LEU2 and rDNA::URA3) also display the Mof(-) phenotype and are also complemented by single and multi-copy 5 S rDNA clones. Mutant 5 S rRNAs expressed from a plasmid as 20-50% of total 5 S rRNA in a wild-type host also induced the Mof(-) phenotype. The increase in frameshifting is greatest when the lacZ reporter gene is expressed on a high copy, episomal vector. No differences were found in 5 S rRNA copy number or electrophoretic mobilities in mof9 strains. Both mof9 and rDNA::LEU2 increase the efficiency of +1 frameshifting as well but have no effect on readthrough of UAG or UAA termination codons, indicating that not ail translational specificity is affected. These data suggest a role for 5 S rRNA in the maintenance of frame in translation. C1 NIDDKD, BIOCHEM PHARMACOL LAB, GENET SIMPLE EUKARYOTES SECT, BETHESDA, MD 20892 USA. OI Dinman, Jonathan/0000-0002-2402-9698 NR 67 TC 36 Z9 38 U1 0 U2 0 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD SEP PY 1995 VL 141 IS 1 BP 95 EP 105 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA RR171 UT WOS:A1995RR17100010 PM 8536994 ER PT J AU JUDD, BH AF JUDD, BH TI MUTATIONS OF ZESTE THAT MEDIATE TRANSVECTION ARE RECESSIVE ENHANCERS OF POSITION-EFFECT VARIEGATION IN DROSOPHILA-MELANOGASTER SO GENETICS LA English DT Article ID WHITE INTERACTION; ULTRABITHORAX PROMOTER; PAIRING DEPENDENCE; MOLECULAR ANALYSIS; GENE-REGULATION; 3RD CHROMOSOME; CHROMATIN; EXPRESSION; PROTEIN; TRANSCRIPTION AB Evidence is presented demonstrating that mutations of zeste, particularly the null state, are strong recessive enhancers of position-effect variegation (PEV) for the white, roughest and Notch loci. The zeste locus encodes a DNA-binding protein that acts as a transcription factor and mediates transvection phenomena at several loci. Its involvement with these seemingly diverse phenomena suggests that the normal zeste product functions in the decondensation of chromatin. A model is presented proposing that zeste is important for opening and stabilizing domains of chromatin, a step in gene determination and the establishment of cell memory. It postulates that chromatin domains that have been structurally modified by chromosomal rearrangement or by insertion of transposable elements are particularly sensitive to the absence or modification of the zeste protein. Such a view unifies the role of zeste in transcription, transvection and PEV. C1 NIEHS,GENET LAB,RES TRIANGLE PK,NC 27709. NR 62 TC 31 Z9 31 U1 0 U2 2 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD SEP PY 1995 VL 141 IS 1 BP 245 EP 253 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA RR171 UT WOS:A1995RR17100022 PM 8536972 ER PT J AU HER, C AKSOY, IA KIMURA, S BRANDRIFF, BF WASMUTH, JJ WEINSHILBOUM, RM AF HER, C AKSOY, IA KIMURA, S BRANDRIFF, BF WASMUTH, JJ WEINSHILBOUM, RM TI HUMAN ESTROGEN SULFOTRANSFERASE GENE (STE) - CLONING, STRUCTURE, AND CHROMOSOMAL LOCALIZATION SO GENOMICS LA English DT Article ID MOLECULAR-CLONING; PHENOL SULFOTRANSFERASE; SEQUENCE-ANALYSIS; RAT-LIVER; DEHYDROEPIANDROSTERONE SULFOTRANSFERASE; HYDROXYSTEROID SULFOTRANSFERASE; MOUSE-LIVER; CDNA; EXPRESSION; FORM AB Sulfation is an important pathway in the metabolism of estrogens. We recently cloned a human liver estrogen sulfotransferase (EST) cDNA. We have now determined the structure and chromosomal localization of the EST gene, STE, as a step toward molecular genetic studies of the regulation of EST in humans. STE spans approximately 20 kb and consists of 8 exons, ranging in length from 95 to 181 bp. The locations of most exon-intron splice junctions within STE are identical to those found in a human phenol ST (PST) gene, STM, and in a rat PST gene, In addition, the locations of five STE introns are also conserved in the human dehydroepiandrosterone (DHEA) ST gene, STD. The 5'-flanking region of STE contains one CCAAT and two TATA sequences. The location of one of the TATA box elements is in excellent agreement with the site of transcription initiation as determined by 5'-rapid amplification of cDNA ends. STE was mapped to human chromosome 4q13.1 by fluorescence in situ hybridization, Cloning and structural characterization of STE will now make it possible to study potential molecular genetic mechanisms involved in the regulation of EST in human tissues. (C) 1995 Academic Press, Inc. C1 MAYO CLIN & MAYO FDN,MAYO MED SCH,DEPT PHARMACOL,ROCHESTER,MN 55905. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. LAWRENCE LIVERMORE NATL LAB,CTR HUMAN GENOME,BIOL & BIOTECHNOL RES PROGRAM,LIVERMORE,CA 94550. UNIV CALIF IRVINE,COLL MED,DEPT BIOL CHEM,NATL HUMAN GENOME RES CTR,IRVINE,CA 92717. FU NHGRI NIH HHS [HG00834]; NIGMS NIH HHS [R01 GM 35720, R01 GM 28157] NR 49 TC 41 Z9 44 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD SEP 1 PY 1995 VL 29 IS 1 BP 16 EP 23 DI 10.1006/geno.1995.1210 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RU604 UT WOS:A1995RU60400003 PM 8530066 ER PT J AU COPELAND, NG GILBERT, DJ SCHINDLER, C ZHONG, Z WEN, Z DARNELL, JE MUI, ALF MIYAJIMA, A QUELLE, FW IHLE, JN JENKINS, NA AF COPELAND, NG GILBERT, DJ SCHINDLER, C ZHONG, Z WEN, Z DARNELL, JE MUI, ALF MIYAJIMA, A QUELLE, FW IHLE, JN JENKINS, NA TI DISTRIBUTION OF THE MAMMALIAN STAT GENE FAMILY IN MOUSE CHROMOSOMES SO GENOMICS LA English DT Article ID INTERFERON-ALPHA; LINKAGE MAP; MURINE; TRANSCRIPTION; PROTEINS; ISGF-3 AB Studies of transcriptional activation by interferons and a variety of cytokines have led to the identification of a family of proteins that serve as signal transducers and activators of transcription, Stats. Here, we report that the seven mouse Stat loci map in three clusters, with each cluster located on a different mouse autosome. The data suggest that the family has arisen via a tandem duplication of the ancestral locus, followed by dispersion of the linked loci to different mouse chromosomes. (C) 1995 Academic Press, Inc. C1 ROCKEFELLER UNIV, MOLEC CELL BIOL LAB, NEW YORK, NY 10021 USA. DNAX RES INST MOLEC & CELLULAR BIOL INC, DEPT CELL BIOL, PALO ALTO, CA 94304 USA. ST JUDE CHILDRENS RES HOSP, DEPT BIOCHEM, MEMPHIS, TN 38105 USA. RP COPELAND, NG (reprint author), NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,POB B, BLDG 539, FREDERICK, MD 21702 USA. FU NCI NIH HHS [P30 CA21765, N01-CO-4600]; NIAID NIH HHS [AI32489] NR 28 TC 135 Z9 138 U1 0 U2 3 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 SEP 1 PY 1995 VL 29 IS 1 BP 225 EP 228 DI 10.1006/geno.1995.1235 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RU604 UT WOS:A1995RU60400028 PM 8530075 ER PT J AU QIU, Y KRISHNAN, V ZENG, Z GILBERT, DJ COPELAND, NG GIBSON, L YANGFENG, T JENKINS, NA TSAI, MJ TSAI, SY AF QIU, Y KRISHNAN, V ZENG, Z GILBERT, DJ COPELAND, NG GIBSON, L YANGFENG, T JENKINS, NA TSAI, MJ TSAI, SY TI ISOLATION, CHARACTERIZATION, AND CHROMOSOMAL LOCALIZATION OF MOUSE AND HUMAN COUP-TF-I AND COUP-TF-II GENES SO GENOMICS LA English DT Article ID STEROID-RECEPTOR SUPERFAMILY; RETINOIC ACID RECEPTORS; TRANSCRIPTION FACTOR; THYROID-HORMONE; RESPONSE ELEMENTS; VITAMIN-D; PROMOTER; ORGANIZATION; MEMBER AB Chicken ovalbumin upstream promoter transcription factors (COUP-TFs) are orphan members of the steroid/thyroid hormone receptor superfamily. COUP-TF homologues have been cloned in many species, from Drosophila to human. The protein sequences of COUP-TFs are highly homologous across species, suggesting functional conservation. Two COUP-TF genes have been cloned from human, and their genomic organizations have been characterized. To determine whether the genomic organization is conserved between human and mouse, we isolated two mouse COUP-TF genes (I and II) and characterized their genomic structures. Both genes have relatively simple structures that are similar to those of their human counterparts. In addition, we mapped mouse COUP-TF I to the distal region of chromosome 13 and COUP-TF II to the central region of chromosome 7. Furthermore, we mapped human COUP-TF I to 5q14 of chromosome 5 and COUP-TF II to 15q26 of chromosome 15. The results demonstrate that COUP-TF genes are located in chromosomal regions that are syntenic between mouse and human. (C) 1995 Academic Press, Inc C1 BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. YALE UNIV,SCH MED,DEPT GENET,CYTOGENET LAB,NEW HAVEN,CT 06520. FU NIDDK NIH HHS [DK 44988, DK 45641] NR 25 TC 28 Z9 31 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD SEP 1 PY 1995 VL 29 IS 1 BP 240 EP 246 DI 10.1006/geno.1995.1237 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RU604 UT WOS:A1995RU60400030 PM 8530078 ER PT J AU KWAN, SP HAGEMANN, TL BLAESE, RM ROSEN, FS AF KWAN, SP HAGEMANN, TL BLAESE, RM ROSEN, FS TI A HIGH-RESOLUTION MAP OF GENES, MICROSATELLITE MARKERS, AND NEW DINUCLEOTIDE REPEATS FROM UBE1 TO THE GATA LOCUS IN THE REGION XP11.23 SO GENOMICS LA English DT Article ID HUMAN X-CHROMOSOME; WISKOTT-ALDRICH SYNDROME; PROXIMAL SHORT ARM; SYNAPSIN-I; LINKAGE; LOCALIZATION; MOUSE; DNA; AMINOTRANSFERASE; LIBRARIES AB Several new genes and markers have recently been identified on the proximal short arm of the human X chromosome in the area of Xp11.23. We had previously generated a YAC contig in this region extending from UBE1 to the OATL1 locus. In this report two polymorphic dinucleotide repeats, DXS6949 and DXS6950, were isolated and characterized from the OATL1 locus, A panel of YAC deletion derivatives from the distal portion of the contig was used in conjunction with the rest of the YAC map to position the new microsatellites and order other markers localizing to this interval. The marker order was determined to be DXS1367-ZNF81-DXS6849-ZNF21-DXS6616-DXS6950-DXS6949. In the proximal region below OATL1, we have isolated a pair of YACs from the GATA locus, B1026 and C01160. Mapping within these YACs indicates the orientation of DXS1126 and DXS1240, while a cosmid near the OATL1 region reveals the overlap between the YAC contigs from the two loci. This cosmid contains the gene respon sible for Wiskott-Aldrich syndrome (WAS) and localizes the disease gene between OATL1 and GATA, These data enable the expansion of the present physical map of the X chromosome from UBE1 to the GATA locus, covering a large portion of the Xp11.23 region, Genetic crossovers in Xp11.23 support the marker orientation and the position of WAS, contrary to previous reports, With the integration of both physical and genetic maps we have predicted the following marker order: Xpter-UBE1-SYN1/ARAF1/TIMP1-DXS1367-ZNF81-DXS6849-ZNF21-DXSy6616- (OATL1, DXS6950-DXS6949)-WAS-(GATA,DXS1126)-DXS1240-Xcen. This orientation identifies DXS6949 and DXS1126 as the nearest flanking polymorphic markers for WAS and provides useful anchor positions for the analysis of other disease genes that have been localized to this area including three differential retinal defects and X-linked nephrolithiasis. (C) 1995 Academic Press, Inc. C1 RUSH MED SCH,DEPT IMMUNOL,CHICAGO,IL 60612. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. FU NCRR NIH HHS [RR02172]; NIAID NIH HHS [AI31587, AI31541] NR 39 TC 15 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD SEP 1 PY 1995 VL 29 IS 1 BP 247 EP 252 DI 10.1006/geno.1995.1238 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RU604 UT WOS:A1995RU60400031 PM 8530079 ER PT J AU POLYMEROPOULOS, MH IDE, S SOARES, MB LENNON, GG AF POLYMEROPOULOS, MH IDE, S SOARES, MB LENNON, GG TI SEQUENCE CHARACTERIZATION AND GENETIC-MAPPING OF THE HUMAN VSNL1 GENE, A HOMOLOG OF THE RAT VISININ-LIKE PEPTIDE RNVP1 SO GENOMICS LA English DT Note ID PROTEIN; CLONING AB In the course of isolation and sequence analysis of microsatellite repeat containing human cDNAs, we have isolated the human homologue of the rat visinin-like peptide gene. The human gene shows a high degree of conservation at both the amino acid and the DNA sequence level. The (CA)(n) microsatellite repeat embedded in the 3' untranslated region of the gene is conserved between rat and human, along with the flanking DNA sequences. We have mapped the VSNL1 gene to the short arm of chromosome 2. (C) 1995 Academic Press, Inc C1 COLUMBIA UNIV COLL PHYS & SURG,DEPT PSYCHIAT,NEW YORK,NY 10032. NEW YORK STATE PSYCHIAT INST & HOSP,NEW YORK,NY 10032. LAWRENCE LIVERMORE NATL LAB,CTR HUMAN GENOME,LIVERMORE,CA 94551. RP POLYMEROPOULOS, MH (reprint author), NIH,NATL CTR HUMAN GENOME RES,GENET DIS RES LAB,BLDG 49,ROOM 4A66,BETHESDA,MD 20892, USA. NR 10 TC 21 Z9 22 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD SEP 1 PY 1995 VL 29 IS 1 BP 273 EP 275 DI 10.1006/geno.1995.1244 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RU604 UT WOS:A1995RU60400037 PM 8530085 ER PT J AU KOZAK, CA GAO, JL MURPHY, PM AF KOZAK, CA GAO, JL MURPHY, PM TI MAPPING OF THE MOUSE MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA RECEPTOR GENE SCYA3R AND 2 RELATED MOUSE BETA-CHEMOKINE RECEPTOR-LIKE GENES TO CHROMOSOME-9 SO GENOMICS LA English DT Note ID FUNCTIONAL EXPRESSION AB Macrophage inflammatory protein-1 alpha (MIP-1 alpha) and RANTES are members of the beta chemokine family of leukocyte chemoattractants. We have previously cloned three mouse genes by cross-hybridization with the human MIP-1 alpha/RANTES receptor gene CMKBR1. One of the mouse genes, Scya3r, encodes a functional MIP-1 alpha receptor. The functions of the other two, Scycc3r-rs1 and Scya3r-rs2, are not known. We have now mapped Scya3r, Scya3r-rs1, and Scya3r-rs2 to chromosome 9, in a region of conserved synteny with the location of CMKBR1. Thus, like chemokine genes and or chemokine receptor genes, this group of beta chemokine receptor genes arose by tandem duplication. (C) 1995 Academic Press, Inc. C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NR 17 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD SEP 1 PY 1995 VL 29 IS 1 BP 294 EP 296 DI 10.1006/geno.1995.1250 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RU604 UT WOS:A1995RU60400043 PM 8530091 ER PT J AU WEISS, B MERTZ, A SCHROCK, E KOENEN, M RAPPOLD, G AF WEISS, B MERTZ, A SCHROCK, E KOENEN, M RAPPOLD, G TI ASSIGNMENT OF A HUMAN HOMOLOG OF THE MOUSE HTR3 RECEPTOR GENE TO CHROMOSOME 11Q23.1-Q23.2 SO GENOMICS LA English DT Note ID INSITU HYBRIDIZATION; 5-HT3 RECEPTORS; TRANSLOCATION; CHANNEL; ILLNESS; FAMILY C1 UNIV HEIDELBERG,INST HUMAN GENET,D-69120 HEIDELBERG,GERMANY. MAX PLANCK INST MED RES,W-6900 HEIDELBERG,GERMANY. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NR 16 TC 16 Z9 16 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD SEP 1 PY 1995 VL 29 IS 1 BP 304 EP 305 DI 10.1006/geno.1995.1254 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RU604 UT WOS:A1995RU60400047 PM 8530095 ER PT J AU BRAZIER, AM PALMER, MH AF BRAZIER, AM PALMER, MH TI COLLECTING CLEAN-CATCH URINE IN THE NURSING-HOME - OBTAINING THE UNCONTAMINATED SPECIMEN SO GERIATRIC NURSING LA English DT Article ID TRACT INFECTIONS; BACTERIURIA C1 NINR,GERONTOL RES CTR,CLIN THERAPEUT LAB,BALTIMORE,MD. RP BRAZIER, AM (reprint author), JOHNS HOPKINS UNIV,SCH NURSING,BALTIMORE,MD 21218, USA. NR 25 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0197-4572 J9 GERIATR NURS JI Geriatr. Nurs. PD SEP-OCT PY 1995 VL 16 IS 5 BP 217 EP 224 DI 10.1016/S0197-4572(05)80167-3 PG 8 WC Geriatrics & Gerontology; Gerontology; Nursing SC Geriatrics & Gerontology; Nursing GA RX609 UT WOS:A1995RX60900005 PM 7590457 ER PT J AU TAYLOR, RR LINNOILA, RI GERARDTS, J TENERIELLO, MG NASH, JD PARK, RC BIRRER, MJ AF TAYLOR, RR LINNOILA, RI GERARDTS, J TENERIELLO, MG NASH, JD PARK, RC BIRRER, MJ TI ABNORMAL EXPRESSION OF THE RETINOBLASTOMA GENE IN OVARIAN NEOPLASMS AND CORRELATION TO P53 AND K-RAS MUTATIONS SO GYNECOLOGIC ONCOLOGY LA English DT Article ID CANCER; OVEREXPRESSION AB We analyzed the expression of the retinoblastoma (Rb) gene in a group of ovarian neoplasms previously characterized for mutations in the p53 suppressor gene and the Ki-ras oncogene, Using immunohistochemical techniques, a total of 59 ovarian neoplasms spanning the histiologic spectrum from benign to malignant were examined for the expression of the Rb protein. All benign cystic adenomas and low malignant potential tumors exhibited normal expression of the Rb protein, Abnormalities in Rb protein staining were noted in 3 of 22 (14%) ovarian carcinomas. The staining patterns included tumors that were totally or focally negative for Rb protein. One tumor focally expressed Rb. This tumor demonstrated a direct juxtaposition of sections of Rb expressing and nonexpressing malignant epithelial cells. Two of the three tumors with abnormal Rb expression also had p53 mutations and staining on serial sections demonstrated that selected ovarian cancer cells possessed mutations in both oncogenes. These data suggest that the loss of Rb gene expression may play a role in the pathogenesis of a small number of invasive ovarian malignancies, but not in noninvasive ovarian neoplasms. C1 NCI, EDCOP, BRPB, DIV CANC PREVENT & CONTROL, ROCKVILLE, MD 20850 USA. NATL NAVAL MED CTR, DEPT OBSTET & GYNECOL GYNECOL ONCOL, BETHESDA, MD 20889 USA. WALTER REED ARMY MED CTR, DEPT OBSTET & GYNECOL GYNECOL ONCOL, WASHINGTON, DC 20307 USA. UNIV N CAROLINA, DEPT SURG PATHOL, CHAPEL HILL, NC 27514 USA. NR 15 TC 19 Z9 19 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD SEP PY 1995 VL 58 IS 3 BP 307 EP 311 DI 10.1006/gyno.1995.1235 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA RU141 UT WOS:A1995RU14100005 PM 7545631 ER PT J AU CALLAHAN, JJ SHEPARD, DS BEINECKE, RH LARSON, MJ CAVANAUGH, D AF CALLAHAN, JJ SHEPARD, DS BEINECKE, RH LARSON, MJ CAVANAUGH, D TI MENTAL-HEALTH SUBSTANCE-ABUSE TREATMENT IN MANAGED CARE - THE MASSACHUSETTS MEDICAID EXPERIENCE SO HEALTH AFFAIRS LA English DT Article; Proceedings Paper CT 7th Biennial Research Conference on the Economics of Mental Health CY SEP 19-20, 1994 CL NIMH, BETHESDA, MD SP NIMH HO NIMH AB Massachusetts was the first state to introduce a statewide specialty mental health managed care plan for its Medicaid program. This study assesses the impact of this program on expenditures, access, and relative quality. Over a one year period, expenditures were reduced by 22 percent below predicted levels without managed care, without any overall reduction in access or relative quality. Reduced lengths-of stay, lower prices, and fewer inpatient admissions were the major factors. However, for one population segment-children and adolescents-readmission rates increased slightly, and providers for this group were less satisfied than they were before managed care was adopted. Less costly types of twenty-four hour care were substituted for inpatient hospital care. This experience supports the usefulness of a managed care program for mental health and substance abuse services, and the applicability of such a program to high-risk populations. C1 HARVARD UNIV,SCH PUBL HLTH,CAMBRIDGE,MA 02138. SUFFOLK UNIV,DEPT PUBL MANAGEMENT,BOSTON,MA 02114. BRANDEIS UNIV,INST HLTH POLICY,SUBST ABUSE GRP,WALTHAM,MA 02254. RP CALLAHAN, JJ (reprint author), BRANDEIS UNIV,HELLER SCH,NIMH,TRAINING PROGRM MENTAL HLTH SERV RES,WALTHAM,MA 02254, USA. NR 19 TC 148 Z9 148 U1 2 U2 2 PU PROJECT HOPE-HEALTH AFFAIRS PI SYRACUSE PA PO BOX 8015, SYRACUSE, NY 13217 SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD FAL PY 1995 VL 14 IS 3 BP 173 EP 184 DI 10.1377/hlthaff.14.3.173 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA RZ723 UT WOS:A1995RZ72300021 PM 7498890 ER PT J AU SULS, J WAN, CK COSTA, PT AF SULS, J WAN, CK COSTA, PT TI RELATIONSHIP OF TRAIT ANGER TO RESTING BLOOD-PRESSURE - A METAANALYSIS SO HEALTH PSYCHOLOGY LA English DT Article DE ANGER; BLOOD PRESSURE; HYPERTENSION ID WHITE-COAT HYPERTENSION; CORONARY HEART-DISEASE; CARDIOVASCULAR REACTIVITY; FAMILIAL DETERMINANTS; NEGATIVE AFFECTIVITY; CYNICAL HOSTILITY; SUPPRESSED ANGER; A BEHAVIOR; FOLLOW-UP; BLACK AB A series of meta-analyses were conducted to assess whether anger is related to essential hypertension. The present review also considered the relevance of the distinction between anger experience and anger expression, the effect of participant selection bias, and the white-coat hypertension effect for the anger-blood pressure (BP) association. Anger experience was correlated with elevated BP, but the relationship was small and highly variable. When positive effects emerged, both participant selection and the reliability of BP measurement posed interpretational problems. Persons high in anger are not merely exhibiting elevated BP in response to testing, so a white-coat effect is not evident. Being labeled as hypertensive may contribute to higher anger scores, however. The review suggests lines of future research concerning associations between trait anger and blood pressure. C1 SUNY ALBANY,DEPT PSYCHOL,ALBANY,NY 12222. NIA,GERONTOL RES CTR,PERSONAL & COGNIT LAB,BALTIMORE,MD 21224. RP SULS, J (reprint author), UNIV IOWA,DEPT PSYCHOL,IOWA CITY,IA 52242, USA. OI Costa, Paul/0000-0003-4375-1712 FU NHLBI NIH HHS [HL 339118] NR 95 TC 84 Z9 87 U1 2 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD SEP PY 1995 VL 14 IS 5 BP 444 EP 456 DI 10.1037//0278-6133.14.5.444 PG 13 WC Psychology, Clinical; Psychology SC Psychology GA RU526 UT WOS:A1995RU52600011 PM 7498116 ER PT J AU AMOUZADEH, HR POHL, LR AF AMOUZADEH, HR POHL, LR TI PROCESSING OF ENDOPLASMIC-RETICULUM LUMINAL ANTIGENS ASSOCIATED WITH HALOTHANE HEPATITIS IN RAT HEPATOCYTES SO HEPATOLOGY LA English DT Article ID PROTEIN DISULFIDE-ISOMERASE; PHOSPHOLIPASE-C-ALPHA; AUTOPHAGIC VACUOLE; SERUM ANTIBODIES; KUPFFER CELLS; LIVER; DEGRADATION; METABOLISM; NEOANTIGENS; MECHANISMS AB In this study we have investigated the mechanism of the processing of trifluoroacetylated liver microsomal protein antigens associated with halothane hepatitis to learn how the immune system might come in contact with these proteins to form antibodies directed against them, Rats were treated with halothane and parenchymal (PC) and non-parenchymal cells (NPC) were isolated 16 hours later, Immunoblotting of the cell lysates with antisera directed against the trifluoroacetyl hapten showed the presence of high levels of trifluoroacetylated proteins in parenchymal cells, whereas none of these proteins were detected in endothelial or Kupffer cells that were isolated by centrifugal elutriation, The half-lives of 100-, 82-, 80-, 63-, 59-, 58-, and 57-kd trifluoroacetylated and native carrier proteins of the trifluoroacetyl hapten in cultures of rat primary parenchymal. cells were approximately 1 day, The turnovers of all of these trifluoroacetylated proteins, except for that of the trifluoroacetylated 100-kd protein, were inhibited by treatment of the cells with ammonium chloride, leupeptin, 4-(2-aminoethyl)-benzenesulfonyl fluoride, or 3-methyladenine (3-RMA). These results indicate that, in liver, the major source of the formation of trifluoroacetylated antigens associated with halothane hepatitis is the parenchymal cells, It appears that most of the trifluoroacetylated antigens and possibly the native carrier protein of the trifluoroacetyl haptens are transferred from the endoplasmic reticulum (ER) to an acidic compartment of PCs, where they are enzymatically degraded, The processing of the trifluoroacetylated proteins by this pathway may be a protective mechanism that prevents these covalently altered proteins from inducing an antibody response in most patients who are administered halothane. RP AMOUZADEH, HR (reprint author), NHLBI,MOLEC IMMUNOL LAB,MOLEC & CELLULAR TOXICOL SECT,BLDG 10,ROOM 8N104,BETHESDA,MD 20892, USA. NR 54 TC 21 Z9 21 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 1995 VL 22 IS 3 BP 936 EP 943 DI 10.1016/0270-9139(95)90318-6 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RT116 UT WOS:A1995RT11600034 PM 7657302 ER PT J AU LAPIS, K BOCSI, J LAPIS, P THORGEIRSSON, UP AF LAPIS, K BOCSI, J LAPIS, P THORGEIRSSON, UP TI FLOW CYTOMETRIC DNA-PLOIDY AND PROLIFERATIVE ACTIVITY OF DIETHYLNITROSAMINE-INDUCED HEPATOCELLULAR-CARCINOMA AND PULMONARY METASTASES IN MONKEYS SO HEPATOLOGY LA English DT Article ID PRIMARY BREAST-CANCER; S-PHASE FRACTION; NUCLEAR-DNA; PROGNOSTIC-SIGNIFICANCE; RAT-LIVER; CHEMICAL HEPATOCARCINOGENESIS; PRENEOPLASTIC FOCI; SOLID TUMORS; CELLS; PROGRESSION AB Flow cytometric DNA analysis was carried out on diethylnitrosamine (DEN) induced primary hepatocellular lar carcinomas (HCC) and lung metastases in monkeys, In analyzing one sample from each of 113 HCC cases, 76 (67.2%) were diploid and 37 (32.7%) aneuploid When more samples were analyzed from the same tumorous liver, all of the 76 diploid cases maintained their pattern, whereas 5 (13.5%) of the aneuploid cases displayed both diploid and aneuploid DNA. Studies of lung metastases from 44 (28 diploid, 16 aneuploid) HCC cases showed that the DNA-ploidy pattern characterizing the primary HCC was preserved in the metastases in 78.6% of the diploid and 93.7% of the aneuploid cases. The average synthetic phase fraction (SPF) value for the diploid tumors was 7.7% and the aneuploid tumors 14.9%. The difference is highly significant (P < .01), Highly significant correlation was found between the DNA ploidy and the SPF values, both in the primary HCC (P = .0001) and the metastases (P = .0266). Of different tumor and host features examined, statistically significant correlation was only found between DNA-ploidy/SPF and the cytological tumor grade. This study represents the first DNA-ploidy analysis of HCC in monkeys, The data showed that diploid and aneuploid tumors displayed comparable metastatic potential, The DNA-ploidy pattern was preserved in the metastases in the majority of the cases. C1 BROWN UNIV,MEM HOSP RHODE ISL,SCH MED,DEPT PATHOL,PAWTUCKET,RI 02860. NCI,DIV CANC ETIOL,BETHESDA,MD 20892. RP LAPIS, K (reprint author), SEMMELWEIS UNIV MED,INST PATHOL & EXPTL CANC RES 1,ULLOI UT 26,H-1085 BUDAPEST VIII,HUNGARY. NR 88 TC 7 Z9 7 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 SEP PY 1995 VL 22 IS 3 BP 952 EP 961 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RT116 UT WOS:A1995RT11600036 PM 7657303 ER PT J AU Collins, FS AF Collins, FS TI Evolution of a vision: Genome project origins, present and future challenges, and far-reaching benefits SO HUMAN GENOME NEWS LA English DT Article C1 NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD. US DOE,HUMAN GENOME PROGRAM,WASHINGTON,DC 20585. NR 0 TC 7 Z9 7 U1 0 U2 0 PU HUMAN GENOME MANAGE INF SYSTEM PI OAK RIDGE PA OAK RIDGE NATIONAL LABORATORY, 1060 COMMERCE PARK, OAK RIDGE, TN 37830 SN 1050-6101 J9 HUM GENOME NEWS JI Hum. Genome News PD SEP-DEC PY 1995 VL 7 IS 3-4 BP 2 EP & PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA TQ108 UT WOS:A1995TQ10800002 ER PT J AU REYNOLDS, JE ARNOS, KS LANDA, B STEVENS, CA SALBERT, BA WRIGHT, L DUKE, B HUNT, W MARAZITA, ML PLOUGHMAN, L MACLEAN, C NANCE, WE DIEHL, SR AF REYNOLDS, JE ARNOS, KS LANDA, B STEVENS, CA SALBERT, BA WRIGHT, L DUKE, B HUNT, W MARAZITA, ML PLOUGHMAN, L MACLEAN, C NANCE, WE DIEHL, SR TI ANALYSIS OF LOCUS HETEROGENEITY IN WAARDENBURG-SYNDROME TYPE-1 AND TYPE-2 USING HIGHLY INFORMATIVE MICROSATELLITE MARKERS SO HUMAN HEREDITY LA English DT Article DE HETEROGENEITY; MICROSATELLITE; POLYMORPHISM; LINKAGE; PAX3; DEAFNESS ID DINUCLEOTIDE REPEAT POLYMORPHISM; SYNDROME TYPE-I; LINKAGE ANALYSIS; GENE; CHROMOSOME-2; MUTATION; REGION; MOUSE; PAX-3; RFLPS AB We performed linkage and locus heterogeneity analyses of Waardenburg syndrome (WS) types 1 and 2 using 9 DNA markers from 2q35-q37, including two highly polymorphic microsatellites very closely linked to the PAX3 candidate gene. None of 5 WS type 2 (WS2) families showed linkage to the PAX3 candidate region. We localized the marker D2S102 to less than I cM from PAX3 (led = 33.7, theta = 0), but a complete absence of crossovers prevented determining whether it maps distal or proximal to PAX3. Study of 14 WS type 1 (WS1) families yielded a maximum lod score of 27.81 at PAX3, theta(f) = 0.010, theta = 0.007 assuming homogeneity. However, we found significant evidence of locus heterogeneity, with one family initially classified as WS1 unlinked to the PAX3 region. Reevaluation of the clinical features of this family revealed atypical morphology of inner canthi. This produced the appearance of dystopia canthorum and high W-index scores. While our one unlinked WS1 family exhibits atypical canthal morphology, our type 1 families with classic dystopia appear to be homogeneously linked to PAX3. These and other findings identify precautions that need to be addressed before using PAX3-linked markers for diagnostic purposes. C1 NIDR,DEODP,MOLEC EPIDEMIOL & DIS INDICATORS BRANCH,BETHESDA,MD 20892. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT HUMAN GENET,RICHMOND,VA 23298. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PSYCHIAT,RICHMOND,VA 23298. GALLAUDET UNIV,WASHINGTON,DC. UNIV PITTSBURGH,CTR CLEFT PALATE CRANIOFACIAL,PITTSBURGH,PA. FU NIDCD NIH HHS [DC00038]; NIMHD NIH HHS [263-MD-135764] NR 39 TC 3 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PD SEP-OCT PY 1995 VL 45 IS 5 BP 243 EP 252 DI 10.1159/000154307 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA RT576 UT WOS:A1995RT57600001 PM 7590754 ER PT J AU FUKUSHIMA, K RAMESH, A SRISAILAPATHY, CRS NI, L CHEN, A ONEILL, M VANCAMP, G COUCKE, P SMITH, SD KENYON, JB JAIN, P WILCOX, ER ZBAR, RIS SMITH, RJH AF FUKUSHIMA, K RAMESH, A SRISAILAPATHY, CRS NI, L CHEN, A ONEILL, M VANCAMP, G COUCKE, P SMITH, SD KENYON, JB JAIN, P WILCOX, ER ZBAR, RIS SMITH, RJH TI CONSANGUINEOUS NUCLEAR FAMILIES USED TO IDENTIFY A NEW LOCUS FOR RECESSIVE NON-SYNDROMIC HEARING-LOSS ON 14Q SO HUMAN MOLECULAR GENETICS LA English DT Article ID CONGENITAL CYTOMEGALOVIRUS-INFECTION; ABNORMALITIES; HOMOZYGOSITY; CHILDREN; GENE AB Hearing impairment is inherited most frequently as an autosomal recessive isolated clinical finding (nonsyndromic hearing loss, NSHL). Extreme heterogeneity and phenotypic variability in the audiometric profile preclude pooling of affected families and severely hamper gene mapping by conventional linkage analysis. However, in instances of consanguinity, homozygosity mapping can be used to identify disease loci in small nuclear families. This report demonstrates the power of this technique by identifying a locus for recessive NSHL on 14q (DFNB4). C1 UNIV IOWA,DEPT OTOLARYNGOL,MOLEC OTOLARYNGOL RES LABS,IOWA CITY,IA 52242. UNIV MADRAS,DEPT GENET,MADRAS,TAMIL NADU,INDIA. UNIV ANTWERP,DEPT MED GENET,B-2610 ANTWERP,BELGIUM. BOYS TOWN NATL RES HOSP,OMAHA,NE. NIDOCD,ROCKVILLE,MD. RI Van Camp, Guy/F-3386-2013 OI Van Camp, Guy/0000-0001-5105-9000 NR 32 TC 46 Z9 46 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD SEP PY 1995 VL 4 IS 9 BP 1643 EP 1648 DI 10.1093/hmg/4.9.1643 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA RT124 UT WOS:A1995RT12400026 PM 8541854 ER PT J AU SHENKER, A CHANSON, P WEINSTEIN, LS CHI, P SPIEGEL, AM LOMRI, A MARIE, PJ AF SHENKER, A CHANSON, P WEINSTEIN, LS CHI, P SPIEGEL, AM LOMRI, A MARIE, PJ TI OSTEOBLASTIC CELLS DERIVED FROM ISOLATED LESIONS OF FIBROUS DYSPLASIA CONTAIN ACTIVATING SOMATIC MUTATIONS OF THE G(S)ALPHA GENE SO HUMAN MOLECULAR GENETICS LA English DT Note ID MCCUNE-ALBRIGHT SYNDROME; STIMULATORY G-PROTEIN; HUMAN ENDOCRINE TUMORS; ADENYLYL CYCLASE; ALPHA-SUBUNIT; BONE; CHAIN C1 HOP BICETRE,SERV ENDOCRINOL & MALAD REPROD,F-94275 LE KREMLIN BICETR,FRANCE. HOP LARIBOISIERE,INSERM,U349,F-75010 PARIS,FRANCE. RP SHENKER, A (reprint author), NIDDKD,METAB DIS BRANCH,BLDG 10,ROOM 8C-101,BETHESDA,MD 20892, USA. RI Chanson, Philippe/F-8511-2013; Weinstein, Lee/I-5575-2015 NR 30 TC 52 Z9 52 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD SEP PY 1995 VL 4 IS 9 BP 1675 EP 1676 DI 10.1093/hmg/4.9.1675 PG 2 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA RT124 UT WOS:A1995RT12400033 PM 8541861 ER PT J AU TASSARA, C PEPPER, AE PUCK, JM AF TASSARA, C PEPPER, AE PUCK, JM TI INTRONIC POINT MUTATION IN THE IL2RG GENE CAUSING X-LINKED SEVERE COMBINED IMMUNODEFICIENCY SO HUMAN MOLECULAR GENETICS LA English DT Note ID RECEPTOR GAMMA-CHAIN; FUNCTIONAL COMPONENT; MESSENGER-RNA; GLOBIN GENE; INTERLEUKIN-2; SEQUENCE C1 NIH,NATL CTR HUMAN GENOME RES,GENE TRANSFER LAB,BETHESDA,MD 20892. NR 26 TC 17 Z9 17 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD SEP PY 1995 VL 4 IS 9 BP 1693 EP 1695 DI 10.1093/hmg/4.9.1693 PG 3 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA RT124 UT WOS:A1995RT12400038 PM 8541866 ER PT J AU UNSER, M THEVENAZ, P LEE, CH RUTTIMANN, UE AF UNSER, M THEVENAZ, P LEE, CH RUTTIMANN, UE TI REGISTRATION AND STATISTICAL-ANALYSIS OF PET IMAGES USING THE WAVELET TRANSFORM SO IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE LA English DT Article RP UNSER, M (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BLDG 13,ROOM 3N17,BETHESDA,MD 20892, USA. RI Unser, Michael/A-1550-2008 NR 0 TC 30 Z9 30 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0739-5175 J9 IEEE ENG MED BIOL JI IEEE Eng. Med. Biol. Mag. PD SEP-OCT PY 1995 VL 14 IS 5 BP 603 EP 611 DI 10.1109/51.464777 PG 9 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA RW954 UT WOS:A1995RW95400014 ER PT J AU ROCHE, PA AF ROCHE, PA TI HLA-DM - AN IN-VIVO FACILITATOR OF MHC CLASS-II PEPTIDE LOADING SO IMMUNITY LA English DT Article ID ANTIGEN-PROCESSING MUTANT; INVARIANT CHAIN PEPTIDES; DR MOLECULES; COMPARTMENTS; TRANSPORT; BINDING AB Initiation of cell-mediated immune responses requires processing of intracellular pathogens into peptide fragments and presentation of these fragments to effector T cells. In the past few years, considerable progress has been made in understanding the molecular mechanisms underlying antigen processing and presentation. In particular, recent work has led to an understanding of the function of HLA-DM (DM), a key player in antigen presentation, whose importance was first appreciated only 1 year ago. RP ROCHE, PA (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 24 TC 65 Z9 65 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD SEP PY 1995 VL 3 IS 3 BP 259 EP 262 DI 10.1016/1074-7613(95)90111-6 PG 4 WC Immunology SC Immunology GA RX645 UT WOS:A1995RX64500001 PM 7552991 ER PT J AU COE, JE SCHELL, RF ROSS, MJ AF COE, JE SCHELL, RF ROSS, MJ TI IMMUNE-RESPONSE IN THE HAMSTER - DEFINITION OF A NOVEL IGG NOT EXPRESSED IN ALL HAMSTER STRAINS SO IMMUNOLOGY LA English DT Article ID RESTRICTION AB A new IgG isotype is described in serum from Syrian hamsters. This 7S-IgG is called IgG3 and was isolated from IgG1 and IgG2 because of its great affinity for protein A. The unique antigenic determinants of IgG3 were identified with a specific rabbit antisera. IgG3 is the least expressed IgG subclass in Syrian hamsters, but serum levels increase more than 10-fold after immunization or infection. Although found in all tested outbred strains, IgG3 is expressed in only some of the commercially available inbred strains of Syrian hamsters. Five inbred hamster strains were examined, and in three strains (CB, LHC and MHA) IgG3 was not detected in normal serum or in immune serum, indicating serum levels at least 100-fold less than other normal inbred/outbred hamsters. The results of breeding experiments suggests a single gene defect is responsible for this non-expression of IgG3. Immunodeficiency was not associated with this IgG3 deficiency. Selective deficiencies of immunoglobulin classes/subclasses in experimental animals are rare. The evolution of a similar IgG3 deficiency in these three hamster strains during inbreeding suggests a novel and efficient mechanism for regulation of IgG3 synthesis in the Syrian hamster. C1 UNIV WISCONSIN,WISCONSIN STATE LAB HYG,MADISON,WI 53706. RP COE, JE (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840, USA. NR 32 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD SEP PY 1995 VL 86 IS 1 BP 141 EP 148 PG 8 WC Immunology SC Immunology GA RU446 UT WOS:A1995RU44600021 PM 7590875 ER PT J AU CASCIARI, JJ CHIN, LK LIVESEY, JC BOYLES, D STEEN, RG RASEY, JS AF CASCIARI, JJ CHIN, LK LIVESEY, JC BOYLES, D STEEN, RG RASEY, JS TI GROWTH-RATE, LABELING INDEX, AND RADIATION SURVIVAL OF CELLS GROWN IN THE MATRIGEL THREAD IN-VITRO TUMOR-MODEL SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE MATRIGEL; TUMOR; RADIATION RESPONSE; EMT6; 9L ID BASEMENT-MEMBRANE MATRIX; MAGNETIC-RESONANCE SPECTROSCOPY; PLASMINOGEN-ACTIVATOR; GENE-EXPRESSION; MAMMALIAN-CELLS; X-RAYS; INVITRO; INVIVO; COMPONENTS; SPHEROIDS AB Six rodent cell lines (36B10 rat glioma cells, 9L rat gliosarcoma cells, V79 Chinese hamster lung fibroblasts, EMT6/UW and EMT6/Ro mouse mammary sarcoma cells, and RIF-1 mouse fibrosarcoma cells) were tested for growth in cylindrical threads of Matrigel. These cells grew in the threads with doubling times of 17-23 h, reaching maximum cell densities on the order of 10(8) cells/ml. Histological sections of these threads showed a heterogeneous cell distribution: cells grew to confluence at the thread surface and at somewhat lower cell densities in the thread core. [H-3]thymidine labeling index and radiation sensitivity were measured for 9L and EMT6/UW cells in Matrigel threads. For both cell types, the labeling index in Matrigel was lower than observed in cell monolayers, with higher labeling indexes at the thread periphery than in the thread core. When these threads were grown in stirred medium, lower thread diameters, higher cell yields per thread, and higher labeling indices were obtained. EMT6 cell monolayers coated with Matrigel were less radiosensitive than cells in uncoated monolayers. This protective effect was eliminated by irradiating in the presence of 1 mg/ml misonidazole. EMT6 cells consume nearly three times as much oxygen (mole/cm(3)-sec) as do 9L cells, which are equally radiosensitive in monolayers with or without a Matrigel coating. The radiation sensitivity of EMT6/UW cells in Matrigel threads was similar to that for monolayers of plateau phase cells, whereas for 9L cells, the response in threads was more similar to exponentially growing cells. We conclude that Matrigel threads provide an alternative in vitro model for studying the radiation response of cells in a three-dimensional geometry. C1 UNIV WASHINGTON, MED CTR, DEPT RADIAT ONCOL, SEATTLE, WA 98195 USA. UNIV WASHINGTON, MED CTR, DEPT RADIOL, SEATTLE, WA 98195 USA. NCI, MOLEC PHARMACOL LAB, BETHESDA, MD 20892 USA. ST JUDE CHILDRENS RES HOSP, DEPT DIAGNOST IMAGING, MEMPHIS, TN 38101 USA. OI Steen, R. Grant/0000-0003-3386-6575 NR 38 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD SEP PY 1995 VL 31 IS 8 BP 582 EP 589 PG 8 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA RT711 UT WOS:A1995RT71100006 ER PT J AU TAYLOR, CE AF TAYLOR, CE TI CYTOKINES AS ADJUVANTS FOR VACCINES - ANTIGEN-SPECIFIC RESPONSES DIFFER FROM POLYCLONAL RESPONSES SO INFECTION AND IMMUNITY LA English DT Review ID B-CELL RESPONSES; INTERFERON-GAMMA; ANTIBODY-PRODUCTION; T-CELLS; BACTERIAL POLYSACCHARIDE; IGE RESPONSE; IFN-GAMMA; MICE; ACTIVATION; SUPPRESSION RP TAYLOR, CE (reprint author), NIAID,DIV MICROBIOL & INFECT DIS,RESP DIS BRANCH,6003 EXECUT BLVD,ROCKVILLE,MD 20892, USA. NR 49 TC 28 Z9 29 U1 0 U2 1 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 SEP PY 1995 VL 63 IS 9 BP 3241 EP 3244 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RQ792 UT WOS:A1995RQ79200001 PM 7543878 ER PT J AU SU, H CALDWELL, HD AF SU, H CALDWELL, HD TI CD4(+) T-CELLS PLAY A SIGNIFICANT ROLE IN ADOPTIVE IMMUNITY TO CHLAMYDIA-TRACHOMATIS INFECTION OF THE MOUSE GENITAL-TRACT SO INFECTION AND IMMUNITY LA English DT Article ID GAMMA-INTERFERON; LISTERIA-MONOCYTOGENES; MURINE LEISHMANIASIS; B-CELLS; MICE; SECRETION; INHIBITION; INTERLEUKIN-6; SALPINGITIS; PROTECTION AB The ability of CD4(+) and CD8(+) T cells to adoptively immunize mice against Chlamydia trachomatis infection of the mouse genital tract was studied. Adoptive transfer experiments were performed with splenic CD4(+) or CD8(+) T cells obtained from mice following resolution of a primary genital tract infection and after a secondary chlamydial challenge. The results show that donor CD4(+) T cells, but not CD8(+) T cells, obtained from mice following resolution of a primary infection or after secondary challenge were effective in transferring significant antichlamydial immunity to the genital tracts of naive animals, The lymphokine profiles in the culture supernatants of proliferating Chlamydia-specific CD4(+) T cells obtained from mice following resolution of a primary infection and after secondary challenge were assayed by an enzyme-linked immunoadsorbent assay, Protective CD4(+) T cells restimulated in vitro secreted interleukin 2, gamma interferon, and interleukin 6, lymphokine profiles characteristic of both Th1- and Th2-like responses, Resting CD4(+) T cells obtained from mice 4 months following resolution of a primary infection were also capable of conferring significant levels of adoptive protective immunity to naive mice. These findings support an important role for CD4(+) T cells in acquired immunity to chlamydial infection of the genital tract and indicate that protective CD4(+) immune responses in this model are relatively long lived. C1 NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,IMMUNOL SECT,HAMILTON,MT 59840. NR 37 TC 187 Z9 192 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 1995 VL 63 IS 9 BP 3302 EP 3308 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RQ792 UT WOS:A1995RQ79200010 PM 7642259 ER PT J AU RAINA, A PANNELL, L KOCHANSKY, J JAFFE, H AF RAINA, A PANNELL, L KOCHANSKY, J JAFFE, H TI PRIMARY STRUCTURE OF A NOVEL NEUROPEPTIDE ISOLATED FROM THE CORPORA CARDIACA OF PERIODICAL CICADAS HAVING ADIPOKINETIC AND HYPERTREHALOSEMIC ACTIVITIES SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE ADIPOKINETIC HORMONE; NEUROPEPTIDE; CORPORA CARDIACA; LIPID MOBILIZATION; PERIODICAL CICADA; MAGICICADA SPECIES; NEZARA VIRIDULA ID CORPUS CARDIACUM; HORMONE; NOMENCLATURE AB A new neuropeptide hormone was isolated from the corpora cardiaca of the periodical cicadas, Magicicada species, Primary structure of the peptide as determined by a combination of automated Edman degradation after enzymatic deblocking with pyroglutamate aminopeptidase and mass spectrometery is: pGlu-Val-Asn-Phe-Ser-Pro-Ser-Trp-Gly-Asn-NH2. Synthetic peptide assayed in the green stink bug Nezara viridula caused a 112% increase in hemolymph lipids at a dose of 0.625 pmol, and a 67% increase in hemolymph carbohydrates at a dose of 2.5 pmol, Based on these results we designate this peptide, a first from order Homoptera, as Magicicada species-adipokinetic hormone (Mcsp-AKH). C1 NIDDKD,ANALYT CHEM LAB,BETHESDA,MD 20892. NINCDS,PROT PEPTIDE SEQUENCING FACIL,NEUROCHEM LAB,BETHESDA,MD 20892. RP RAINA, A (reprint author), USDA ARS,INSECT NEUROBIOL & HORMONE LAB,BELTSVILLE,MD 20705, USA. NR 15 TC 9 Z9 9 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0965-1748 J9 INSECT BIOCHEM MOLEC JI Insect Biochem. Mol. Biol. PD SEP PY 1995 VL 25 IS 8 BP 929 EP 932 DI 10.1016/0965-1748(95)00032-Q PG 4 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA RV027 UT WOS:A1995RV02700007 PM 7550248 ER PT J AU Veech, RL Kashiwaya, Y King, MT AF Veech, RL Kashiwaya, Y King, MT TI The resting membrane potential of cells are measures of electrical work, not of ionic currents SO INTEGRATIVE PHYSIOLOGICAL AND BEHAVIORAL SCIENCE LA English DT Article ID CYSTIC-FIBROSIS; GENERATION AB Living cells create electric potential force, E, between their various phases by at least three distinct mechanisms. Charge separation, F = Q(1)Q(2)/4 Pi epsilon(o) epsilon(r)r(2) (Eqn 1) creates the potential, E = Q/4 Pi epsilon(o) epsilon(r)r of -120 to -145 mV between cytoplasmic and mitochondrial phases by unbalanced proton expulsion powered by the redox energy of the respiratory chain. Electrically unbalanced flow of Naf through voltage gated Naf channels raises the potential of nerve from -85 to +30 mV. The so-called resting potential of cells, which varies from -85 mV in heart to -4.5 mV in red cell, does not appear to result from the unbalanced flow of ions between phases, but rather to be a measure of the work required to move ions between phases. Movement of an ion between phases entails three types of energy. Concentration work is that required to move an ion between phases containing different concentrations of ions: Delta G(Concentration energy) = RT ln [ion(Z)](out)/[ion(Z)](in) (Eqn 2) Electrical work is that work required to move an ion from phases with differing electric potentials: Delta G(Electrical energy) = zFE[ion(z)](out/in) (Eqn 3). The Nernst potential of an ion existing at different concentrations in two phases is: E[ion(z)](out/in) = RT/zF ln [ion(Z)](out)/[ion(Z)](in) (Eqn 4) The osmotic work term is small and can generally be ignored. In heart the measured resting potential between extra- and intracellular phases, E(N) is = -85 mV. The calculated Nernst potential of K+, E [K+](out/in), is -85 mV (Eqn 4). This means that in heart, K+ distributes itself between the two phases as if it moved through an open ion channel. Its concentration work (Eqn 2) is equal in magnitude but opposite in sign to its electrical work (Eqn 3). This makes net K+ current flow, I, equal O, indicating that this potential cannot be a diffusion potential. In liver the resting potential ranges from -28 to -40 mV, and is equivalent to the E[Cl-](+)(out/in), while in red cell the resting potential is about -4.5 mV, which is equivalent to the potential of all nine major inorganic ion species except Na+, K+ and Ca2+. Therefore the resting potential between extra- and intracellular phases of cells should be thought of, not as a diffusion potential but rather as a measure of the electrical work: E(out/in) = RTln[permeant ion(z)](out/in)/zF, (Eqn 5) required to transport the most permeant ions in a Gibbs-Donnan near-equilibrium system, either K+ or Cl- or both, between the phases of an aqueous system during the flow of current required to measure potentials with intracellular KCI electrodes or during ion movements brought about during normal cellular activity. The resting electrical potential results from the existence of a mono-ionic Gibbs-Donnan near-equilibrium system between the extra- and intracellular phases of cell wherein the activity of free H2O within all phases of the system is equal and the energy of the gradients of the nine major inorganic ions, Delta G[ion(z)](out/in), are in near-equilibrium with one another, with the potential between the phases, E(N) and with the energy of ATP hydrolysis. Delta G(ATP Hydrolysis) ranges from a low of -55 to slightly over -60 kJ/mole in all cell types. While the classic inanimate Gibbs-Donnan system has only one ratio of ion concentrations between phases, r, cellular Gibbs-Donnan systems have three different r's representing three different equal energy ion groups or quanta, Delta G[ion(z)](out/in). In heart, the quanta of Delta G [Na+](out/in), [Mg2+](out/in) and [H2PO4-](out/in) was 1/3 of Delta G(ATP Hydrolysis); the quanta of Delta G [H+](out/in), [HCO3-](out/in) and [Cl-](out/in) quanta was 1/3 of Delta G[Na+](out/in). The Delta G [K+](out/in) in heart or Delta G[Cl-](out/in) in liver is O and represents the resting potential. In all cell types, a drop in the Delta G(ATP Hydrolysis) resulting from anoxic or most other forms of injury decreases the extent of the Na+ gradients between extra- and intracellular phases. This leads to a steoreotypic response characterized by gain of intracellular Na+, loss of intracellular K+, decrease in resting potential and gain in intracellular H2O. A better understanding of the nature of the electrical potential between the extra- and intracellular phases of cells gives new insights into the relationship of fluid and ion changes that occur in cellular injury and apoptosis, the nature and treatment of cardiac arrhythmias and refractory seizures, as well as states of altered gene expression, such as malignant transformation and common diseases of ion transport. RP Veech, RL (reprint author), NIAAA,METAB & MOLEC BIOL LAB,DEPT HLTH & HUMAN SERV,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 46 TC 12 Z9 13 U1 0 U2 2 PU TRANSACTION PERIOD CONSORTIUM PI NEW BRUNSWICK PA DEPT 3091 RUTGERS-THE STATE UNIV OF NJ, NEW BRUNSWICK, NJ 08903 SN 1053-881X J9 INTEGR PHYS BEH SCI JI Integr. Physiol. Behav. Sci. PD SEP-DEC PY 1995 VL 30 IS 4 BP 283 EP 307 DI 10.1007/BF02691602 PG 25 WC Psychology, Biological; Neurosciences SC Psychology; Neurosciences & Neurology GA TN867 UT WOS:A1995TN86700004 PM 8788226 ER PT J AU Goldberg, TE Weinberger, DR AF Goldberg, TE Weinberger, DR TI Thought disorder, working memory and attention: Interrelationships and the effects of neuroleptic medications SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT Lundbeck Symposium on Drug Treatment of Schizophrenia - From Molecular Biology to Patients Subjective Experience CY JUN 09-10, 1995 CL COPENHAGEN, DENMARK SP H Lundbeck A S Gramt DE schizophrenia; neurocognition; neuroleptics; disorder; working memory; attention ID SCHIZOPHRENIC-PATIENTS; PERFORMANCE AB Impairments in attention and vigilance, working memory and organization of speech (thought disorder) have been reliably observed in patients with schizophrenia. The response in these cognitive parameters to neuroleptic medications can be used to sharpen their characterization in neuropsychological terms. In particular, a review of the literature suggests that while working memory is relatively insensitive to neuroleptics attention and thought disorder may improve with neuroleptic administration. On the basis of the response to typical and atypical neuroleptics attention as deployed in the Continuous Performance Test may reflect response readiness rather than actual vigilance. Thought disorder, which is often assumed to be the result of impaired discourse planning due to a reduced capacity for working memory, does not covary with working memory, and the two parameters show different responses to neuroleptic medications. Rather, cognitive studies suggest that thought disorder may arise from abnormalities within the semantic system itself. C1 NIMH,IRP,CLIN BRAIN DISORDERS BRANCH,NIH,WASHINGTON,DC 20032. NR 46 TC 43 Z9 43 U1 3 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0268-1315 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD SEP PY 1995 VL 10 SU 3 BP 99 EP 104 DI 10.1097/00004850-199509000-00013 PG 6 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA TV461 UT WOS:A1995TV46100013 PM 8866771 ER PT J AU STGEORGIEV, V AF STGEORGIEV, V TI TREATMENT AND EXPERIMENTAL THERAPEUTICS OF BLASTOMYCOSIS SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS LA English DT Review ID RESPIRATORY-DISTRESS SYNDROME; NORTH-AMERICAN BLASTOMYCOSIS; LIPOSOMAL-AMPHOTERICIN-B; HIGH-DOSE KETOCONAZOLE; MURINE PULMONARY BLASTOMYCOSIS; INVITRO ANTIFUNGAL ACTIVITIES; CENTRAL-NERVOUS-SYSTEM; HISTOPLASMA-CAPSULATUM; FUNGAL-INFECTIONS; CANDIDA-ALBICANS RP NIAID, SOLAR BLDG, ROOM 4C-04, BETHESDA, MD 20892 USA. NR 183 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-8579 EI 1872-7913 J9 INT J ANTIMICROB AG JI Int. J. Antimicrob. Agents PD SEP PY 1995 VL 6 IS 1 BP 1 EP 12 PG 12 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA RZ206 UT WOS:A1995RZ20600001 ER PT J AU RAUTAHARJU, PM MANOLIO, TA FURBERG, CD SISCOVICK, D NEWMAN, AB BORHANI, NO GARDIN, JM AF RAUTAHARJU, PM MANOLIO, TA FURBERG, CD SISCOVICK, D NEWMAN, AB BORHANI, NO GARDIN, JM TI ISCHEMIC EPISODES IN 24-H AMBULATORY ELECTROCARDIOGRAMS OF ELDERLY PERSONS - THE CARDIOVASCULAR HEALTH STUDY SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE HOLTER ECG; ST-T ABNORMALITIES; ISCHEMIA; CIRCADIAN VARIATION; DIGITALIS; OBESITY ID ACUTE MYOCARDIAL-INFARCTION; LEFT-VENTRICULAR HYPERTROPHY; CORONARY-ARTERY DISEASE; SUDDEN CARDIAC DEATH; CIRCADIAN VARIATION; HEART-RATE; DAILY LIFE; ECG; PREVALENCE; POPULATION AB We examined correlates of ischemic episodes in 24-h ambulatory electrocardiograms (ECG) in a sample of 1511 men and women 65 years old and older. Ischemic episodes had a high prevalence period during early afternoon and also during morning hours after awakening, and the overall prevalence was 13% in men and 9% in women (P < 0.001 for gender difference). The prevalence was 9.6% in participants with no history of myocardial infarction and no major or minor resting ECG abnormalities. In multivariate analysis by logistic regression, being on digitalis medication was associated with over a three-fold risk of ischemic episodes, with an odds ratio (95% confidence limits) of 3.21 (1.80 to 5.74). Left ventricular hypertrophy by ECG and atrial fibrillation had almost a three-fold excess risk of ischemic episodes, with odds ratios 2.81 (1.37 to 5.74) and 2.63 (1.17 to 5.91), respectively. Isolated ST-T abnormalities had almost a two-fold excess of ischemic episodes, with an odds ratio of 1.89 (1.01 to 3.54). Being overweight was associated with a 33% reduced likelihood of ischemic episodes after adjustment for other factors, with an odds ratio of 0.67 (0.46 to 0.98). It is concluded that the prevalence of silent ischemic episodes is high in older men and women. C1 NHLBI,BETHESDA,MD 20892. UNIV WASHINGTON,DEPT MED,SEATTLE,WA. UNIV WASHINGTON,DEPT EPIDEMIOL,SEATTLE,WA 98195. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT EPIDEMIOL,PITTSBURGH,PA. UNIV WASHINGTON,CHS,CTR COORDINATING,SEATTLE,WA 98195. UNIV CALIF IRVINE,DEPT MED,IRVINE,CA 92717. RP RAUTAHARJU, PM (reprint author), BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,PIEDMONT PLAZA 2,SUITE 505,200 W 1ST ST,WINSTON SALEM,NC 27104, USA. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NHLBI NIH HHS [N01-HC-85079, N01-HC-85080, N01-HC-85081] NR 33 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD SEP PY 1995 VL 51 IS 2 BP 165 EP 175 DI 10.1016/0167-5273(95)02414-R PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RX720 UT WOS:A1995RX72000009 PM 8522413 ER PT J AU SAXENA, A ROBERTSON, JT KUFTA, C STETLERSTEVENSON, WG ALI, IU AF SAXENA, A ROBERTSON, JT KUFTA, C STETLERSTEVENSON, WG ALI, IU TI INCREASED EXPRESSION OF GELATINASE-A AND TIMP-2 IN PRIMARY HUMAN GLIOBLASTOMAS SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE GELATINASE A; TIMP-2; GLIOBLASTOMAS ID EXTRACELLULAR-MATRIX PROTEINS; EPIDERMAL GROWTH-FACTOR; HUMAN-BRAIN-TUMORS; RAT GLIOMA-CELLS; TISSUE INHIBITOR; IV COLLAGENASE; METALLOPROTEINASE INHIBITOR; BREAST-CARCINOMA; FACTOR RECEPTOR; INVITRO AB The highly invasive growth of glioblastomas may be a consequence of an abnormal profile of proteinases and proteinase inhibitors involved in remodeling of the basement membrane and normal vasculature. We have detected a 1.5-3-fold increase in the transcription of gelatinase A and TIMP-2 (Tissue Inhibitor of Metalloproteinase) in glioblastomas as compared to the normal brain tissue. Increased expression of gelatinase A and TIMP-2 in these tumors was also evident by immunohistochemical analysis. Our data suggest that increased expression and perturbation of the balance between metalloproteinases and their inhibitors that are involved in extracellular matrix remodeling and angiogenesis may contribute to the invasive phenotype of glioblastomas. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. UNIV TENNESSEE,DEPT NEUROSURG,MEMPHIS,TN 38119. NINCDS,SURG NEUROL BRANCH,BALTIMORE,MD. NCI,PATHOL LAB,BETHESDA,MD 20892. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 45 TC 10 Z9 10 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD SEP PY 1995 VL 7 IS 3 BP 469 EP 473 PG 5 WC Oncology SC Oncology GA RM685 UT WOS:A1995RM68500007 PM 21552861 ER PT J AU LIANG, BC AF LIANG, BC TI DIRECT ISOLATION OF VARIABLY AMPLIFIED CDNAS FROM HUMAN TUMOR-CELL LINES SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE GENE AMPLIFICATION; HUMAN TUMOR CELL LINES ID MAMMALIAN DNA; RECEPTOR GENE; AMPLIFICATION; HYBRIDIZATION; SEQUENCES AB Gene amplification is an important phenomenon in the pathogenetics of malignancy. A method is defined which allows the determination of gene amplification from any sample from which RNA can be obtained, and requires no a priori knowledge of the cytogenetic or genomic state of the tumor. This method allows the determination of various degrees of amplification, and is sensitive to lower degrees of increased copy number. Gene amplification from cell lines with known oncogene amplification of 13- and 7-fold could be detected. Hence, use of a simple modified subtractive hybridization technique can identify amplified cDNAs from tissue without detailed previous genomic knowledge of the samples. This methodology should prove useful in the assessment of disorders where copy number changes of expressed genes are present. C1 NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,CLIN PHARMACOL BRANCH,BETHESDA,MD. NR 29 TC 6 Z9 6 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD SEP PY 1995 VL 7 IS 3 BP 611 EP 615 PG 5 WC Oncology SC Oncology GA RM685 UT WOS:A1995RM68500026 PM 21552880 ER PT J AU MANSOURI, A HENLE, KJ NAGLE, WA PARKER, RJ REED, E AF MANSOURI, A HENLE, KJ NAGLE, WA PARKER, RJ REED, E TI PARTIAL CHARACTERIZATION OF A CISPLATIN-RESISTANT SUBLINE OF MURINE RIF-1 TUMOR-CELLS SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE CISPLATIN RESISTANCE; DRUG RESISTANCE; TUMOR DRUG RESISTANCE; HYPERTHERMIA; RADIATION INDUCED FIBROSARCOMA; ANTINEOPLASTIC AGENTS; GLUTATHIONE ID HUMAN OVARIAN-CANCER; DRUG-RESISTANCE; MULTIDRUG RESISTANCE; REVERSAL; CIS-DIAMMINEDICHLOROPLATINUM(II); QUANTITATION; REPAIR; LINES; CHEMOTHERAPY; ACCUMULATION AB We have developed a drug-resistant cell line (RIF/Ptr1) (R) from the murine radiation-induced fibrosarcoma (RIF-1) also designated Pts or (S). This subline has been characterized previously by an increased resistance to cisplatin (cis-diamminedichloroplatinum(II) or CDDP), lowered intracellular CDDP concentrations, and elevated intracellular glutathione (GSH) levels (1.4-2.5-fold) but unaltered formation of CDDP-DNA interstrand cross-links. In this work, we have shown that RIF/Ptr1 cells were also resistant to carmustine (BCNU) and X-irradiation. Neither cell line had P-glycoprotein 170. The intrastrand CDDP-DNA adduct level was proportional to the concentration of intracellular CDDP. The oxygen consumption, ATP level, and glycolysis were similar in both cell lines. The cisplatin influx and efflux showed that the RIF/Ptr1 cells had lower drug influx and higher drug efflux compared to RIF-1. We conclude that the major difference between the cisplatin sensitive and cisplatin-resistant cells in this model is the regulation of cisplatin transport probably at the cell membrane level suggesting that a membrane active transport system other than P-glycoprotein 170 is involved. Whether glutathione is linked to the putative membrane transporter needs further investigation. C1 LOUISIANA STATE UNIV,MED CTR,SHREVEPORT,LA. UNIV ARKANSAS MED SCI HOSP,JOHN L MCCLELLAN MEM VET HOSP,DEPT MED,LITTLE ROCK,AR. UNIV ARKANSAS MED SCI HOSP,JOHN L MCCLELLAN MEM VET HOSP,DEPT PHYSIOL BIOPHYS,LITTLE ROCK,AR. UNIV ARKANSAS MED SCI HOSP,JOHN L MCCLELLAN MEM VET HOSP,DEPT RADIOL,LITTLE ROCK,AR. NCI,BETHESDA,MD 20892. RP MANSOURI, A (reprint author), OVERTON BROOKS VAMC,DEPT MED,510 E STONER AVE,SHREVEPORT,LA 71101, USA. NR 35 TC 0 Z9 0 U1 1 U2 1 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD SEP PY 1995 VL 7 IS 3 BP 649 EP 656 PG 8 WC Oncology SC Oncology GA RM685 UT WOS:A1995RM68500032 PM 21552886 ER PT J AU LEE, J JIAO, XD GENTLEMAN, S WETZEL, MG OBRIEN, P CHADER, GJ AF LEE, J JIAO, XD GENTLEMAN, S WETZEL, MG OBRIEN, P CHADER, GJ TI SOLUBLE-BINDING PROTEINS FOR DOCOSAHEXAENOIC ACID ARE PRESENT IN NEURAL RETINA SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE DOCOSAHEXAENOIC ACID; DOCOSAHEXAENOIC ACID BINDING PROTEIN; FATTY ACID-BINDING PROTEINS; OMEGA-3 FATTY ACIDS; PHOTORECEPTOR; RETINA ID GROWTH-FACTOR RECEPTOR; FATTY-ACIDS; RAT-LIVER; DEFICIENCY; BRAIN; METABOLISM; TISSUES; LIPIDS; CELLS AB Purpose. To determine if soluble binding proteins (BP) for fatty acids (FA), particularly docosahexaenoic acid (DHA), could be identified in the cytosol of rat and bovine retinas under in vitro and in vivo conditions. Methods. In vitro, cytosol fractions from normal bovine and rat retinas were delipidated and incubated with [C-14]-DHA with or without a number of competing fatty acids. After crosslinking bound FA to BP, the proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and radioactivity determined in each fraction. For in vivo experiments, rats received [C-14]-DHA by gavage. At selected periods after ingestion, retinas were collected and cytosolic fractions were prepared from each. These were crosslinked and subjected to SDS-PAGE, and radioactivity was determined in each fraction. Results. In vitro, several peaks of radioactivity (approximately 13, 20, 32, 43-45, 50, 63, and 94-105 kd) were found that exhibited [C-14]-DHA binding. Relative specificity of binding was assessed by blocking of the [C-14]-DHA binding with unlabeled DHA and by competition experiments with other FAs. After in vivo ingestion of [C-14]-DHA, a large peak of radioactivity was observed at 43 kd by 4 hours. At 6 hours, this peak decreased and, after 24 hours, it approached baseline. Conclusions. These findings demonstrate that there is a discrete grouping of proteins in retinal cytosol capable of binding DHA and other FA. Although the identities of these proteins have yet to be determined, the group may include a member of the 12- to 15-kd group of small fatty acid binding proteins (FABP). In particular, a unique 43-kd binding peak could play a major role in the uptake, binding, or both of DHA by the retina in vivo. C1 UNIV KANSAS,DEPT PHYSIOL & CELL BIOL,LAWRENCE,KS 66045. HLTH RES ASSOCIATES,ROCKVILLE,MD. RP LEE, J (reprint author), NEI,RETINAL CELL & MOLEC BIOL LAB,9000 ROCKVILLE PIKE,ROOM 332,BETHESDA,MD 20892, USA. NR 28 TC 9 Z9 9 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 1995 VL 36 IS 10 BP 2032 EP 2039 PG 8 WC Ophthalmology SC Ophthalmology GA RR516 UT WOS:A1995RR51600011 PM 7657541 ER PT J AU BATTJES, RJ PICKENS, RW BROWN, LS AF BATTJES, RJ PICKENS, RW BROWN, LS TI HIV-INFECTION AND AIDS RISK BEHAVIORS AMONG INJECTING DRUG-USERS ENTERING METHADONE TREATMENT - AN UPDATE SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HIV; AIDS RISK BEHAVIORS; INJECTING DRUG USE; TRENDS ID HUMAN-IMMUNODEFICIENCY-VIRUS; NEW-YORK-CITY; HETEROSEXUAL TRANSMISSION; UNITED-STATES; ABUSERS AB Trends in HIV infection and AIDS risk behaviors among injecting drug users (IDUs) were assessed through a series of nonblinded point-prevalence surveys conducted between 1987 and 1991 with admissions to methadone treatment in eight areas, including New York City; Asbury Park and Trenton, New Jersey; Philadelphia; Baltimore; Chicago; San Antonio, Texas; and Los Angeles County. Over the 5-year period, significant changes in HIV seropositivity were found in two of the eight cities, with seroprevalence decreasing in Asbury Park from 43.1 to 21.2% and increasing from 10.1 to 17.6% in Chicago. Initially high levels of injection-related risk behaviors decreased substantially across cohorts in most cities, except for San Antonio and Los Angeles, where risk levels remained high. Sexual risk behaviors continued at high levels in all cities, suggesting relatively little sexual risk reduction during the course of the study. C1 NATL INST DRUG ABUSE,ADDICT RES CTR,BALTIMORE,MD 21224. ADDICT RES TREATMENT CORP,BROOKLYN,NY. RP BATTJES, RJ (reprint author), NIDA,5600 FISHERS LANE,ROOM 10A-38,ROCKVILLE,MD 20857, USA. NR 21 TC 47 Z9 47 U1 2 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD SEP 1 PY 1995 VL 10 IS 1 BP 90 EP 96 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RR296 UT WOS:A1995RR29600013 PM 7648291 ER PT J AU WESTERGAARD, GC SUOMI, SJ AF WESTERGAARD, GC SUOMI, SJ TI THE MANUFACTURE AND USE OF BAMBOO TOOLS BY MONKEYS - POSSIBLE IMPLICATIONS FOR THE DEVELOPMENT OF MATERIAL CULTURE AMONG EAST-ASIAN HOMINIDS SO JOURNAL OF ARCHAEOLOGICAL SCIENCE LA English DT Article DE BAMBOO; CAPUCHIN; CEBUS; HOMO ERECTUS; MONKEY; TOOL-MANUFACTURE; TOOL-USE ID CEBUS-APELLA; WILD CHIMPANZEES; CAPUCHIN AB This research examined the manufacture and use of bamboo tools by capuchin monkeys (Cebus apella). We presented groups of subjects with bamboo, and apparatus that accommodated the use of probing and cutting tools. Four monkeys manufactured probing tools by breaking bamboo strips, detaching shoots from larger branches, and removing leaves and stubs. A fifth subject used probing tools but did not modify them. In a second experiment five capuchins manufactured bamboo cutting tools. A sixth subject used cutting tools but did not modify them. These results demonstrate a simple bamboo-tool technology in capuchins. We hypothesize that east Asian Homo erectus could have used similar or more advanced manufacturing techniques to produce bamboo tools suitable for purposes that included probing and cutting. (C) 1995 Academic Press Limited RP WESTERGAARD, GC (reprint author), NICHHD,COMPARAT ETHOL LAB,POB 529,POOLESVILLE,MD 20837, USA. NR 24 TC 11 Z9 13 U1 0 U2 2 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0305-4403 J9 J ARCHAEOL SCI JI J. Archaeol. Sci. PD SEP PY 1995 VL 22 IS 5 BP 677 EP 681 DI 10.1016/S0305-4403(95)80153-7 PG 5 WC Anthropology; Archaeology; Geosciences, Multidisciplinary SC Anthropology; Archaeology; Geology GA RX419 UT WOS:A1995RX41900010 ER PT J AU TROPP, BE RAGOLIA, L XIA, WM DOWHAN, W MILKMAN, R RUDD, KE IVANISEVIC, R SAVIC, DJ AF TROPP, BE RAGOLIA, L XIA, WM DOWHAN, W MILKMAN, R RUDD, KE IVANISEVIC, R SAVIC, DJ TI IDENTITY OF THE ESCHERICHIA-COLI CLS AND NOV GENES SO JOURNAL OF BACTERIOLOGY LA English DT Note ID CARDIOLIPIN SYNTHESIS; PHOSPHOLIPID-COMPOSITION; PHOSPHATIDYLSERINE; AMPLIFICATION; CONSEQUENCES; NOVOBIOCIN; SYNTHASE AB cls and nov mutants have similar increased sensitivities to novobiocin and reduced levels of cardiolipin, both of which can be corrected by plasmid-borne copies of either wild-type gene. A comparison of the DNA sequences of both genes further verifies their identity. C1 UNIV TEXAS,SCH MED,DEPT BIOCHEM & MOLEC BIOL,HOUSTON,TX 77225. UNIV IOWA,DEPT SCI BIOL,IOWA CITY,IA 52242. NATL LIB MED,NATL BIOTECHNOL CTR,BETHESDA,MD 20894. INST MOLEC GENET & GENET ENGN,YU-11001 BELGRADE,YUGOSLAVIA. RP TROPP, BE (reprint author), CUNY QUEENS COLL,DEPT CHEM & BIOCHEM,FLUSHING,NY 11367, USA. RI xia, weiming/E-5465-2016 OI xia, weiming/0000-0002-7463-3295 FU NIGMS NIH HHS [GM 20487] NR 19 TC 22 Z9 23 U1 0 U2 1 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 SEP PY 1995 VL 177 IS 17 BP 5155 EP 5157 PG 3 WC Microbiology SC Microbiology GA RR981 UT WOS:A1995RR98100045 PM 7665497 ER PT J AU WOFSY, C KENT, UM MAO, SY METZGER, H GOLDSTEIN, B AF WOFSY, C KENT, UM MAO, SY METZGER, H GOLDSTEIN, B TI KINETICS OF TYROSINE PHOSPHORYLATION WHEN IGE DIMERS BIND TO FC-EPSILON RECEPTORS ON RAT BASOPHILIC LEUKEMIA-CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RBL-2H3 MAST-CELLS; IMMUNOGLOBULIN-E; SIGNAL TRANSDUCTION; HISTAMINE-RELEASE; ANTIGEN-BINDING; CROSS-LINKING; DESENSITIZATION; AFFINITY; AGGREGATION; COMPLEXES AB Previously, we demonstrated that aggregates of the high affinity receptor for IgE (Fc epsilon RI), formed by the binding of chemically cross-linked oligomers of IgE, continue to signal early and late cellular responses long after the formation of new aggregates is blocked. In the present work, we explore quantitatively the relationship between aggregation of the receptors and one of the earliest biochemical changes this initiates. We compare the time course of aggregate formation, inferred from studies of the binding of dimers of IgE, and the time course of phosphorylation of tyrosines on receptor subunits when the receptors are aggregated. A simple model does not fit the data. It appears that aggregates formed late in the response are less effective signaling units than those formed initially. We propose new explanations for the persistence of the response and the unusual kinetics. C1 LOS ALAMOS NATL LAB,DIV THEORET,THEORET BIOL & BIOPHYS GRP,LOS ALAMOS,NM 87545. UNIV NEW MEXICO,DEPT MATH & STAT,ALBUQUERQUE,NM 87131. NIAMS,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM35556] NR 54 TC 24 Z9 24 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 1 PY 1995 VL 270 IS 35 BP 20264 EP 20272 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RR584 UT WOS:A1995RR58400008 PM 7544786 ER PT J AU NOMIZU, M KIM, WH YAMAMURA, K UTANI, A SONG, SY OTAKA, A ROLLER, PP KLEINMAN, HK YAMADA, Y AF NOMIZU, M KIM, WH YAMAMURA, K UTANI, A SONG, SY OTAKA, A ROLLER, PP KLEINMAN, HK YAMADA, Y TI IDENTIFICATION OF CELL-BINDING SITES IN THE LAMININ ALPHA-1 CHAIN CARBOXYL-TERMINAL GLOBULAR DOMAIN BY SYSTEMATIC SCREENING OF SYNTHETIC PEPTIDES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SOLID-PHASE SYNTHESIS; AMINO-ACID-SEQUENCE; A-CHAIN; HEPARIN-BINDING; NEUROMUSCULAR-JUNCTION; MULTIDOMAIN PROTEIN; NEURITE OUTGROWTH; IKVAV SEQUENCE; ADHESION; FIBRONECTIN AB The laminin al chain carboxyl-terminal globular domain has been identified as a site of multiple biological activities. Using a systematic screening for cell binding sites with 113 overlapping synthetic peptide beads that covered this domain, we found 19 potential active sequences. Corresponding synthetic peptides were evaluated for direct cell attachment, spreading, and inhibition of cell spreading to a laminin-1 substrate using several cell lines. Five peptides (AG-10, AG-22, AG-32, AG-56, and AG-73) showed cell attachment activities with cell-type specificities. Cell spreading on AG-10 was inhibited by beta 1 and alpha 6 integrin antibodies and on AG-32 was inhibited by beta 1, alpha 2, and alpha 6 integrin antibodies. In contrast, cell adhesion and spreading on peptide AG-73 were not inhibited by these antibodies. The minimum active sequences of AG-10, AG-32, and AG-73 were determined to be SIYITRF, IAFQRN, and LQVQLSIR, respectively. These sequences are highly conserved among the different species and different laminin alpha chains, suggesting that they play a critical role for biological function and for interaction with cell surface receptors. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. RP NOMIZU, M (reprint author), NIDR,DEV BIOL LAB,BLDG 30,BETHESDA,MD 20892, USA. RI Kim, Wooho/G-3703-2011 NR 58 TC 195 Z9 198 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 1 PY 1995 VL 270 IS 35 BP 20583 EP 20590 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RR584 UT WOS:A1995RR58400055 PM 7657636 ER PT J AU FARROW, NA ZHANG, OW SZABO, A TORCHIA, DA KAY, LE AF FARROW, NA ZHANG, OW SZABO, A TORCHIA, DA KAY, LE TI SPECTRAL DENSITY-FUNCTION MAPPING USING N-15 RELAXATION DATA EXCLUSIVELY SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE PROTEIN DYNAMICS; SPECTRAL DENSITY FUNCTION; N-15 RELAXATION ID NUCLEAR MAGNETIC-RESONANCE; MODEL-FREE APPROACH; BACKBONE DYNAMICS; NMR RELAXATION; SPECTROSCOPY; MACROMOLECULES; PROTEINS; DIFFUSION; BINDING; CHAIN AB A method is presented for the determination of values of the spectral density function, J(omega), describing the dynamics of amide bond vectors from N-15 relaxation parameters alone. Assuming that the spectral density is given by the sum of Lorentzian functions, the approach allows values of J(omega) to be obtained at omega=0, omega(N), and 0.870 omega(H), where omega(N) and omega(H) are Larmor frequencies of nitrogen and proton nuclei, respectively, from measurements of N-15 T-1, T-2 and H-1-N-15 steady-state NOE values at a single spectrometer frequency. Alternatively, when measurements are performed at two different spectrometer frequencies of i and j MHz, J(omega) can be mapped at omega=0, omega(N)(i), omega(N)(j), 0.870 omega(H)(i) and 0.870 omega Hj, where omega Ni, for example, is the N-15 Larmor frequency for a spectrometer operating at i MHz. Additionally, measurements made at two different spectrometer frequencies enable contributions to transverse relaxation from motions on millisecond-microsecond time scales to be evaluated and permit assessment of whether a description of the internal dynamics is consistent with a correlation function describing the dynamics of the N-15-NH bond vector are necessary, provided that dJ(omega)/d omega is relatively constant between omega=omega(H) + omega(N) to omega=omega(H)-omega(N). Simulations demonstrate that the method is accurate for a wide range of protein motions and correlation times, and experimental data establish the validity of the methodology. Results are presented for a folded and an unfolded form of the N-terminal SH3 domain of the protein drk. C1 UNIV TORONTO,DEPT MED GENET,TORONTO,ON M5S 1A8,CANADA. UNIV TORONTO,DEPT BIOCHEM,TORONTO,ON M5S 1A8,CANADA. UNIV TORONTO,DEPT CHEM,TORONTO,ON M5S 1A8,CANADA. NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. NIDR,BONE RES BRANCH,BETHESDA,MD 20892. RP FARROW, NA (reprint author), UNIV TORONTO,PROT ENGN NETWORK CTR EXCELLENCE,100 COLL ST,TORONTO,ON M5S 1A8,CANADA. RI Szabo, Attila/H-3867-2012 NR 29 TC 379 Z9 381 U1 1 U2 21 PU ESCOM SCI PUBL BV PI LEIDEN PA PO BOX 214, 2300 AE LEIDEN, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD SEP PY 1995 VL 6 IS 2 BP 153 EP 162 PG 10 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA RY392 UT WOS:A1995RY39200006 PM 8589604 ER PT J AU BATES, SE FOJO, AT WEINSTEIN, JN MYERS, TG ALVAREZ, M PAULI, KD CHABNER, BA AF BATES, SE FOJO, AT WEINSTEIN, JN MYERS, TG ALVAREZ, M PAULI, KD CHABNER, BA TI MOLECULAR TARGETS IN THE NATIONAL-CANCER-INSTITUTE DRUG SCREEN SO JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; SOUTHWEST-ONCOLOGY-GROUP; TUMOR-CELL-LINES; CYTOSINE-ARABINOSIDE; PREDNISONE ROAP; COMBINATION; VINCRISTINE; RUBIDAZONE; ADULTS; AGE C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. RP BATES, SE (reprint author), NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,MED BRANCH,BETHESDA,MD 20892, USA. NR 20 TC 32 Z9 32 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-5216 J9 J CANCER RES CLIN JI J. Cancer Res. Clin. Oncol. PD SEP-OCT PY 1995 VL 121 IS 9-10 BP 495 EP 500 DI 10.1007/BF01197759 PG 6 WC Oncology SC Oncology GA RZ791 UT WOS:A1995RZ79100002 PM 7559726 ER PT J AU ROBBINS, AR WARD, RD OLIVER, C AF ROBBINS, AR WARD, RD OLIVER, C TI A MUTATION IN GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE ALTERS ENDOCYTOSIS IN CHO CELLS SO JOURNAL OF CELL BIOLOGY LA English DT Article ID RESOLUTION 2-DIMENSIONAL ELECTROPHORESIS; RECEPTOR-MEDIATED ENDOCYTOSIS; SKELETAL-MUSCLE; GLYCOLYTIC-ENZYMES; TUBULAR LYSOSOMES; CHAIN-REACTION; PROTEINS; MICROTUBULES; BINDING; MACROPHAGES AB The CHO cell mutant FD1,3.25 exhibits both increased accumulation and altered distribution of endocytosed fluid phase tracers. Neither the rate of tracer internalization nor the kinetics of recycling from early endosomes was affected, but exocytosis from late endocytic compartments appeared to be decreased in the mutant. Endocytosed tracer moved more rapidly to the cell poles in FD1.3.25 than in wild type cells, An abundant 36-kD polypeptide was found associated with taxol-polymerized microtubules in preparations from wild type and mutant; in the former but not the latter this polypeptide could be dissociated by incubation of the microtubules in ATP or high salt. The 36-kD polypeptide co-electrophoresed in two dimensions with the monomer of the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Analysis of cDNA clones showed that the mutant is heterozygous for this enzyme, with similar to 25% of the GAPDH RNA containing a single nucleotide change resulting in substitution of Ser for Pro(234), a residue that is conserved throughout evolution. Stable transfectants of wild type cells expressing the mutant monomer at similar to 15% of the total enzyme exhibited the various changes in endocytosis observed in FD1.3.25. C1 NIDR,IMMUNOL LAB,BETHESDA,MD 20892. RP ROBBINS, AR (reprint author), NIDDK,BIOCHEM & METAB LAB,10-9B08,10 CTR DR MSC1800,BETHESDA,MD 20892, USA. NR 52 TC 73 Z9 81 U1 1 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD SEP PY 1995 VL 130 IS 5 BP 1093 EP 1104 DI 10.1083/jcb.130.5.1093 PG 12 WC Cell Biology SC Cell Biology GA RR841 UT WOS:A1995RR84100008 PM 7657694 ER PT J AU RISCO, C MENENDEZARIAS, L COPELAND, TD DASILVA, PP OROSZLAN, S AF RISCO, C MENENDEZARIAS, L COPELAND, TD DASILVA, PP OROSZLAN, S TI INTRACELLULAR-TRANSPORT OF THE MURINE LEUKEMIA-VIRUS DURING ACUTE INFECTION OF NIH 3T3 CELLS - NUCLEAR IMPORT OF NUCLEOCAPSID PROTEIN AND INTEGRASE SO JOURNAL OF CELL SCIENCE LA English DT Article DE MULV; NC PROTEIN; IMMUNOGOLD ID VIRAL-RNA; LOCALIZATION SIGNAL; STRUCTURAL PROTEINS; ZINC FINGER; TYPE-1 REV; DNA; SEQUENCE; COMPLEX; DOMAINS; BINDING AB The entry and intracellular transport of Moloney-murine leukemia virions inside mouse NIH 3T3 cells have been followed by electron microscopy techniques, Five viral proteins- matrix (MA, p15), capsid (CA, p30), nucleocapsid (NC, p10), integrase (IN), and the envelope glycoprotein (SU, gp70) - were located by immunolabeling using gold probes, After entering the cells, viral particles were frequently detected inside cytoplasmic vesicles of variable size, Their viral envelope was apparently lost during intracytoplasmic transport, When the unenveloped viral cores reached the nuclear membrane or its vicinity, they were disrupted, Two of the immunolabeled proteins, NC and IN, were detected entering the nucleus of non-dividing cells, where both were targeted to the nucleolus, However, MA and CA were found only in the cytoplasm, NC is a nucleic acid-binding protein which contains potential nuclear localization signals, We suggest that NC could enter the nucleus as part of a nucleoprotein complex, associated with IN, and possibly, also with viral DNA. C1 DYNCORP,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD. NCI,MATH BIOL LAB,MEMBRANE BIOL SECT,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC VIROL & CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,PROT CHEM GRP,FREDERICK,MD 21702. RI Menendez Arias, Luis /G-2436-2016; OI Menendez Arias, Luis/0000-0002-1251-6640 FU NCI NIH HHS [N01-CO-74101] NR 48 TC 54 Z9 54 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 SEP PY 1995 VL 108 BP 3039 EP 3050 PN 9 PG 12 WC Cell Biology SC Cell Biology GA RV181 UT WOS:A1995RV18100012 PM 8537443 ER PT J AU LAZOWSKI, KW LI, J DELPORTE, C BAUM, BJ AF LAZOWSKI, KW LI, J DELPORTE, C BAUM, BJ TI EVIDENCE FOR THE PRESENCE OF A HG-INHIBITABLE WATER-PERMEABILITY PATHWAY AND AQUAPORIN-1 IN A5 SALIVARY EPITHELIAL-CELLS SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID INTEGRAL MEMBRANE-PROTEIN; CHIP28 PROTEIN; RAT; GLAND; EXPRESSION; CHANNEL; IDENTIFICATION; SECRETION; CDNA; LINE AB The molecular basis of water-permeability in salivary and other exocrine glands is not understood. We have examined two well-studied salivary epithelial cell lines for evidence of a Hg-inhibitable water-permeability pathway. A5 and HSG cells are derived from rat and human submandibular glands, respectively. Only A5 cells demonstrated such a pathway. The rate of A5 cell osmotic shrinkage was inhibited about fivefold in the presence of 300 mu M HgCl2. To determine if this activity was associated with the expression of the prototypical water channel (aquaporin, AQP) AQP1, we used three separate experimental approaches; Northern analysis and reverse transcription-polymerase chain reaction (RT-PCR) analysis of isolated mRNA, and Western analysis of cell membranes. All three methods yielded positive results with A5 cells and negative results with HSG cells. The similar to 800 bp product of RT-PCR was analyzed further by sequencing and restriction enzyme digestion. The results were consistent with the previously reported coding region sequence for rat kidney AQP1. The aggregate data demonstrate that marked differences in water-permeability and water channel expression exist in these two salivary epithelial cell lines. (C) 1995 Wiley-Liss, Inc. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. NR 31 TC 7 Z9 8 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 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD SEP PY 1995 VL 164 IS 3 BP 613 EP 619 DI 10.1002/jcp.1041640320 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA RR002 UT WOS:A1995RR00200019 PM 7544358 ER PT J AU SUYAMA, K SAITO, K CHEN, G PAN, BS MANJI, HK POTTER, WZ AF SUYAMA, K SAITO, K CHEN, G PAN, BS MANJI, HK POTTER, WZ TI ALTERATIONS IN CYCLIC-AMP GENERATION AND G-PROTEIN SUBUNITS FOLLOWING TRANSIENT ISCHEMIA IN GERBIL HIPPOCAMPUS SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE CROSS-TALK; CYCLIC AMP; GERBIL; G PROTEIN; HIPPOCAMPUS; ISCHEMIA ID BETA-GAMMA-SUBUNITS; PHORBOL ESTER TREATMENT; DELAYED NEURONAL DEATH; GTP-BINDING-PROTEINS; RAT-BRAIN; KINASE-C; FOREBRAIN ISCHEMIA; ADENYLYL CYCLASES; CEREBRAL-ISCHEMIA; CALCIUM-UPTAKE AB We examined alterations in the cyclic AMP generating system and G protein subunits in gerbil hippocampus following 10 min of transient ischemia, In hippocampal slices, basal and isoproterenol- and forskolin-stimulated cyclic AMP accumulations were markedly increased at 6 and 24 h after ischemia. Interestingly, both the inhibition of forskolin-stimulated cyclic AMP and the potentiation of beta-adrenoceptor-stimulated cyclic AMP by a gamma-aminobutyric acid, receptor agonist were attenuated at these time points. Ischemia did not affect the immuno-labeling of any of the G protein or subunits; only that of beta subunits was significantly decreased, by 28.2%, 4 days after ischemia. In contrast, pertussis toxin-catalyzed [P-32]ADP ribosylation declined progressively during the late recirculation period, reaching a significant reduction (25.4%) at 6 h after ischemia. These results suggest that ischemia affects the heterotrimeric conformation (alpha beta gamma) of G(i)/G(o) during the recirculation period, thereby leading to increased cyclic AMP production. Because cyclic AMP-dependent protein kinase A modulates the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-kainate receptor channels, postischemic sensitization of the cyclic AMP generating system may contribute to neuronal degeneration in the hippocampus. C1 NIMH,EXPTL THERAPEUT BRANCH,CLIN PHARMACOL SECT,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,BETHESDA,MD 20892. RI Chen, Guang/A-2570-2017 NR 50 TC 12 Z9 13 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD SEP PY 1995 VL 15 IS 5 BP 877 EP 885 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA RQ020 UT WOS:A1995RQ02000018 PM 7673381 ER PT J AU VANHORN, JD MCINTOSH, AR MAISOG, JM AF VANHORN, JD MCINTOSH, AR MAISOG, JM TI COMPLICATIONS IN THE USE OF THE SPM X(2) STATISTIC SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Letter C1 UNIV TORONTO,BAYCREST CTR,ROTMAN RES INST,TORONTO,ON,CANADA. NIMH,PSYCHOL & PSYCHOPATHOL LAB,FUNCT BRAIN IMAGING SECT,BETHESDA,MD 20892. RP VANHORN, JD (reprint author), NIMH,CLIN BRAIN DISORDERS BRANCH,PET UNIT,BETHESDA,MD 20892, USA. RI McIntosh, Anthony/G-4955-2011 NR 11 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD SEP PY 1995 VL 15 IS 5 BP 895 EP 896 PG 2 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA RQ020 UT WOS:A1995RQ02000021 PM 7673384 ER PT J AU ZHOU, HX SZABO, A AF ZHOU, HX SZABO, A TI MICROSCOPIC FORMULATION OF MARCUS THEORY OF ELECTRON-TRANSFER SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID CLASSICAL SOLVENT DYNAMICS; POLAR-SOLVENTS; MOLECULAR-DYNAMICS; DIPOLAR LATTICE; SIMULATION; MODEL AB A microscopic theory for the rate of nonadiabatic electron transfer is developed and its relation to classical Marcus theory is analyzed. The focus is on how the nonlinear response of a molecular solvent to a change in the charge distribution of the donor-acceptor pair influences the rate; quantum mechanical and solvent dynamical effects are ignored. Under these restrictions, the rate is determined by the probability density of the energy gap, which is defined as the instantaneous change in solvation energy upon moving an electron from the donor to the acceptor. It is shown how this probability density can be obtained from the free energies of transferring varying amounts of charge between the donor and acceptor (as specified by a charging parameter). A simple algorithm is proposed for calculating these free-energy changes (and hence the energy gap probability density) from computer simulations on just three states: the reactant, the product, and an ''anti''-product formed by transferring a positive unit charge from the donor to the acceptor. Microscopic generalizations of the Marcus nonequilibrium free-energy surfaces for the reactant and the product, constructed as functions of the charging parameter, are presented. Their relation to surfaces constructed as functions of the energy gap is also established. The Marcus relation (i.e., the activation energy as a parabolic function of the free-energy change of reaction) is derived in a way that clearly shows that it is a good approximation in the normal region even when the solvent response is significantly nonlinear. A simple generalization of this relation, in which the activation energy is given by parabolic functions with different curvatures in the normal and inverted regions, is proposed. These curvatures are inversely proportional to the reorganization energies of the product and the antiproduct, respectively. Computer simulations of a simple model system are performed to illustrate and test these results and procedures. C1 NIDDKD, CHEM PHYS LAB, BETHESDA, MD 20892 USA. RI Szabo, Attila/H-3867-2012; Zhou, Huan-Xiang/M-5170-2016 OI Zhou, Huan-Xiang/0000-0001-9020-0302 NR 33 TC 68 Z9 69 U1 2 U2 17 PU AMER INST PHYSICS PI MELVILLE PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA SN 0021-9606 EI 1089-7690 J9 J CHEM PHYS JI J. Chem. Phys. PD SEP 1 PY 1995 VL 103 IS 9 BP 3481 EP 3494 DI 10.1063/1.470232 PG 14 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA RT923 UT WOS:A1995RT92300023 ER PT J AU KLEIN, KO DEMERS, LM SANTNER, SJ BARON, J CUTLER, GB SANTEN, RJ AF KLEIN, KO DEMERS, LM SANTNER, SJ BARON, J CUTLER, GB SANTEN, RJ TI USE OF ULTRASENSITIVE RECOMBINANT CELL BIOASSAY TO MEASURE ESTROGEN-LEVELS IN WOMEN WITH BREAST-CANCER RECEIVING THE AROMATASE INHIBITOR, LETROZOLE SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BIOSYNTHESIS; CGS-20267 AB The development of well tolerated, potent, specific, and nontoxic aromatase inhibitors for the treatment of postmenopausal women with estrogen-dependent breast cancer has been a major goal of recent studies. The third generation inhibitors now under investigation are nearly 10,000-fold more potent than first generation compounds. Currently available RIAs for plasma estradiol lack sufficient sensitivity to measure levels during aromatase inhibition and, thus, to assess drug potency precisely. The availability of an ultrasensitive bioassay for estradiol provided the opportunity to accurately assess the potency of a new third generation triazole aromatase inhibitor, letrozole (CGS 20267). We used this assay to measure estradiol levels in 14 women with metastatic breast cancer given letrozole at doses of 100 mu g to 5.0 mg/day over a 1a-week period. The lack of differences between doses and sampling times allowed pooling of data. Basal estradiol levels of 7.2 +/- 1.9 pmol/L (mean +/- SEM, 1.95 +/- 0.52 pg/mL) fell to 0.26 +/- 0.11 pmol/L (0.07 +/- 0.03 pg/mL) during the first 6 weeks of therapy and to 0.48 +/- 0.18 pmol/L (0.13 +/- 0.05 pg/mL) during the second 6 weeks of therapy. Although plasma estradiol levels measured by RIA were significantly correlated with levels measured by bioassay (r = 0.79; P < 0.01), the degree of suppression assessed by the bioassay (95 +/- 2% after 6 weeks) was greater than that determined by the RIA (81 +/- 4%), presumably due to improved ability to measure very low estradiol levels. We conclude that plasma estradiol is suppressed by letrozole to lower levels than previously observed, with equivalent suppression at all doses studied. A slight, although not statistically significant, rebound in estradiol levels occurs during the second 6 weeks of therapy compared to the first 6 weeks. Maximum inhibition of aromatase is achieved at letrozole doses as low as 100 mu g. C1 CHILDRENS HOSP ORANGE CTY, ORANGE, CA 92668 USA. PENN STATE UNIV, MILTON S HERSHEY MED CTR, HERSHEY, PA 17033 USA. NICHHD, BETHESDA, MD 20892 USA. WAYNE STATE UNIV, DETROIT, MI 48201 USA. NR 5 TC 40 Z9 41 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1995 VL 80 IS 9 BP 2658 EP 2660 DI 10.1210/jc.80.9.2658 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RU633 UT WOS:A1995RU63300017 PM 7673408 ER PT J AU CELI, FS SILVER, K WALSTON, J KNOWLER, WC BOGARDUS, C SHULDINER, AR AF CELI, FS SILVER, K WALSTON, J KNOWLER, WC BOGARDUS, C SHULDINER, AR TI LACK OF IRS-1 CODON-513 AND CODON-972 POLYMORPHISM IN PIMA-INDIANS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Note ID INSULIN-RECEPTOR SUBSTRATE-1; DEPENDENT DIABETES-MELLITUS; MITOCHONDRIAL-DNA; GLUCOKINASE GENE; MUTATIONS; NIDDM AB Insulin receptor substrate-1 (IRS-1), an endogenous substrate for the insulin receptor tyrosine kinase, mediates many or all of the metabolic actions of insulin. Recently, polymorphism at codons 513 and 972 of the IRS-1 gene resulting in 2 amino acid substitutions that were associated with type II diabetes were found in a Caucasian population. Using allele specific oligonucleotide (ASO) hybridization, we screened 242 diabetic and 190 nondiabetic Pima Indians, a population with a very high prevalence of type II diabetes. Neither of the two mutations was present in either diabetic or nondiabetic subjects. We conclude that polymorphism at codons 513 and 972 of the IRS-1 gene observed in certain Caucasian populations is very rare or absent in Pima Indians. C1 NIA, BALTIMORE, MD 21224 USA. NIDDKD, PHOENIX, AZ USA. NR 20 TC 21 Z9 23 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1995 VL 80 IS 9 BP 2827 EP 2829 DI 10.1210/jc.80.9.2827 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RU633 UT WOS:A1995RU63300045 PM 7673431 ER PT J AU MANOLIO, TA BURKE, GL PSATY, BM NEWMAN, AB HAAN, M POWE, N TRACY, RP OLEARY, DH AF MANOLIO, TA BURKE, GL PSATY, BM NEWMAN, AB HAAN, M POWE, N TRACY, RP OLEARY, DH TI BLACK-WHITE DIFFERENCES IN SUBCLINICAL CARDIOVASCULAR-DISEASE AMONG OLDER ADULTS - THE CARDIOVASCULAR HEALTH STUDY SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE CARDIOVASCULAR DISEASE; AGED; EPIDEMIOLOGY; RACIAL DIFFERENCES; RISK FACTORS; ATHEROSCLEROSIS ID CORONARY HEART-DISEASE; EXTREMITY ARTERIAL-DISEASE; RISK-FACTORS; UNITED-STATES; CEREBRAL ATHEROSCLEROSIS; MORTALITY; HYPERTENSION; LIPOPROTEINS; POPULATIONS; CHOLESTEROL AB Cardiovascular and all-cause mortality are higher in black than white Americans, but racial differences in clinical and subclinical cardiovascular disease (CVD) have not been examined in older adults. Clinical and subclinical CVD and its risk factors were compared in 4926 white and 244 black men and women aged 65 years and older. Black participants had lower socioeconomic status and generally higher prevalences of CVD and its risk factors, except for adverse lipid profiles. Common carotid wall thickness was greater in black than white women, and ankle-arm blood pressure ratios were lower in black women and men (p < 0.01). After adjustment for CVD risk factors, common carotid walls were significantly thicker and ankle-arm ratios were lower in blacks than whites of both sexes, while internal carotid walls were significantly thinner in black women. Racial differences in clinical and subclinical CVD in older adults are similar to those reported in younger populations and do not appear to be explained by CVD risk factors. C1 WAKE FOREST UNIV, BOWMAN GRAY SCH MED, DEPT PUBL HLTH SCI, WINSTON SALEM, NC 27103 USA. UNIV WASHINGTON, DEPT MED, SEATTLE, WA USA. UNIV WASHINGTON, DEPT EPIDEMIOL, SEATTLE, WA USA. UNIV WASHINGTON, DEPT HLTH SERV, SEATTLE, WA USA. UNIV PITTSBURGH, GRAD SCH PUBL HLTH, PITTSBURGH, PA USA. UNIV CALIF DAVIS, DEPT INTERNAL MED, DAVIS, CA USA. JOHNS HOPKINS UNIV, DEPT MED, BALTIMORE, MD USA. UNIV VERMONT, DEPT PATHOL, BURLINGTON, VT 05405 USA. GEISINGER MED CTR, DIV RADIOL, DANVILLE, PA USA. RP MANOLIO, TA (reprint author), NHLBI, DIV EPIDEMIOL & CLIN APPLICAT, FED BLDG, ROOM 301, 7550 WISCONSIN AVE, BETHESDA, MD 20892 USA. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NHLBI NIH HHS [N01-HC 85079, N01-HC 85080, N01-HC 85081] NR 65 TC 71 Z9 71 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-4356 EI 1878-5921 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD SEP PY 1995 VL 48 IS 9 BP 1141 EP 1152 DI 10.1016/0895-4356(94)00240-Q PG 12 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA RM869 UT WOS:A1995RM86900007 PM 7636516 ER PT J AU KLAUSNER, RD AF KLAUSNER, RD TI PRESIDENTIAL-ADDRESS TO THE AMERICAN-SOCIETY-FOR-CLINICAL-INVESTIGATION, SAN-DIEGO, CALIFORNIA, 6 MAY, 1995 - VALUES AND VALUE - THE SURVIVAL OF BIOMEDICAL-RESEARCH SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1995 VL 96 IS 3 BP 1181 EP 1183 DI 10.1172/JCI118148 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RR853 UT WOS:A1995RR85300001 PM 7657788 ER PT J AU FAUST, LP ELBENNA, J BABIOR, BM CHANOCK, SJ AF FAUST, LP ELBENNA, J BABIOR, BM CHANOCK, SJ TI THE PHOSPHORYLATION TARGETS OF P47(PHOX), A SUBUNIT OF THE RESPIRATORY BURST OXIDASE - FUNCTIONS OF THE INDIVIDUAL TARGET SERINES AS EVALUATED BY SITE-DIRECTED MUTAGENESIS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE SUPEROXIDES; PHAGOCYTES; PHOSPHORYLATION; B LYMPHOCYTES; RESPIRATORY BURST ID CHRONIC GRANULOMATOUS-DISEASE; PROTEIN-KINASE-C; HUMAN-NEUTROPHILS; NADPH OXIDASE; BINDING SITE; 2 FORMS; ACTIVATION; COMPONENTS; CELL; STAUROSPORINE AB The respiratory burst oxidase of phagocytes and B lymphocytes catalyzes the reduction of oxygen to O-2(-) at the expense of NADPH. Dormant in resting cells, the oxidase is activated by exposing the cells to appropriate stimuli. During activation, p47(phox), a cytosolic oxidase subunit, becomes extensively phosphorylated on a number of serines located between S303-S379. To determine whether this phosphorylation is necessary for oxidase activation, we examined phorbol-elicited oxidase activity in EBV-transformed B lymphoblasts deficient in p47(phox) after transfection with plasmids expressing various S --> A mutants of p47(phox). The mutant containing S --> A mutations involving all serines between S303 and S379 [S(303-379) A] was not phosphorylated, did not translocate to plasma membrane during activation and was almost devoid of function, As to individual serines, S379 was of special interest because (a) p47(phox) S379 was phosphorylated in phorbol-activated lymphoblasts expressing wild-type p47(phox), and (b) p47(phox) S379A failed to translocate to the membrane, and was as functionless as p47(phox) S(303-379) A; other single S --> A mutations had little effect on oxidase activity. These findings suggest that the phosphorylation of S379 may be important for oxidase activation in whole cells. C1 NCI, PEDIAT BRANCH, BETHESDA, MD 20892 USA. SCRIPPS RES INST, LA JOLLA, CA 92037 USA. FU NCRR NIH HHS [RR-00833]; NIAID NIH HHS [AI-28479, AI-24227] NR 31 TC 139 Z9 139 U1 0 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1995 VL 96 IS 3 BP 1499 EP 1505 DI 10.1172/JCI118187 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RR853 UT WOS:A1995RR85300040 PM 7657821 ER PT J AU AGUILERA, G KISS, A SUNARAKBASAK, B AF AGUILERA, G KISS, A SUNARAKBASAK, B TI HYPERRENINEMIC HYPOALDOSTERONISM AFTER CHRONIC STRESS IN THE RAT SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE RENIN MESSENGER-RNA; ADRENAL; ALDOSTERONE SYNTHETASE; 11 BETA-HYDROXYLASE; ANGIOTENSIN II RECEPTORS ID ADRENAL GLOMERULOSA CELLS; ATRIAL NATRIURETIC FACTOR; ANGIOTENSIN-II RECEPTORS; ALDOSTERONE SECRETION; ZONA GLOMERULOSA; RENIN SECRETION; IMMOBILIZATION STRESS; MESSENGER-RNA; RESPONSES; BIOSYNTHESIS AB The effects of chronic stress on the renin-angiotensin-aldosterone system were studied by analysis of plasma hormone levels, kidney renin mRNA levels, adrenal angiotensin II receptors, and steroidogenesis in rats subjected to repeated immobilization (2 h daily) or intraperitoneal injections of 1.5 M NaCl for 14 d. 24 h after the last stress in both stress models, plasma aldosterone levels were reduced in spite of significant increases in plasma renin activity. Repeatedly intraperitoneal hypertonic saline-injected rats showed plasma renin activity responses to acute immobilization similar to controls, but markedly reduced plasma aldosterone responses. Concomitant with the increases in plasma renin activity, renin mRNA levels in the kidney were significantly increased in intraperitoneal hypertonic saline-injected rats, and these increases were prevented by beta-adrenergic receptor blockade with propranolol. In isolated adrenal glomerulosa cells from chronically stressed rats, maximum aldosterone responses to angiotensin II, ACTH, and 8-Br-cAMP were significantly decreased, whereas pregnenolone responses were increased, P450-aldosterone synthetase mRNA levels and binding of I-125-[Sar(1),Ile(8)] angiotensin II were significantly reduced in the adrenal zona glomerulosa of stressed rats. These studies show that chronic repeated stress leads to renin stimulation due to sympathetic activation, and inhibition of aldosterone secretion due to inhibition of the late steroidogenic pathway. The data provide evidence for a role of chronic stress in the development of hyperreninemic hypoaldosteronism. RP AGUILERA, G (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,ENDOCRINE PHYSIOL SECT,BLDG 10,ROOM 10N262,10 CTR DR,MSC 1862,BETHESDA,MD 20892, USA. NR 49 TC 32 Z9 32 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1995 VL 96 IS 3 BP 1512 EP 1519 DI 10.1172/JCI118189 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RR853 UT WOS:A1995RR85300042 PM 7657823 ER PT J AU XU, X KANG, SH HEIDENREICH, O OKERHOLM, M OSHEA, JJ NERENBERG, MI AF XU, X KANG, SH HEIDENREICH, O OKERHOLM, M OSHEA, JJ NERENBERG, MI TI CONSTITUTIVE ACTIVATION OF DIFFERENT JAK TYROSINE KINASES IN HUMAN T-CELL LEUKEMIA-VIRUS TYPE-1 (HTLV-1) TAX PROTEIN OR VIRUS-TRANSFORMED CELLS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE JAK KINASE, HTLV-1; IL-6; PROLIFERATION; NF-KAPPA-B ID INTERFERON-ALPHA/BETA; KAPPA-B; GENE; EXPRESSION; RECEPTOR; INTERLEUKIN-2; ELEMENT; TUMORS; MICE AB HTLV-1 infection causes an adult T cell leukemia in humans, The viral encoded protein tax, is thought to play an important role in oncogenesis. Our previous data obtained from a tax transgenic mouse model revealed that tax transforms mouse fibroblasts but not thymocytes, despite comparable levels of tax expression in both tissues. Constitutive tyrosine phosphorylation of a 130-kD protein(s) was observed in the tax transformed fibroblast B line and in HTLV-1 transformed human lymphoid lines, but not in thymocytes from Thy-tax transgenic mice. Phosphotyrosine immunoprecipitation followed by Western blot analysis with a set of Jak kinase specific antibodies, identified p130 as Jak2 in the tax transformed mouse fibroblastic cell Line and Jak3 in HTLV-1 transformed human T cell lines. Phosphorylation of Jak2 in tax transformed cells resulted from high expression of IL-6. Tyrosine phosphorylation of this protein could also be induced in Balb/c3T3 cells using a supernatant from the B line, which was associated with induction of cell proliferation. Both phosphorylation and proliferation were inhibited by IL-6 neutralizing antibodies. Constitutive phosphorylation of Jak kinases may facilitate tumor growth in both HTLV-1 infected human T cells and the transgenic mouse model. C1 SCRIPPS RES INST, DEPT MOLEC & EXPTL MED, LA JOLLA, CA 92037 USA. NCI, FREDERICK CANC RES & DEV CTR, EXPTL IMMUNOL LAB, LEUKOCYTE CELL BIOL SECT, FREDERICK, MD 21702 USA. OI Heidenreich, Olaf/0000-0001-5404-6483 FU NCI NIH HHS [CA-5023]; NINDS NIH HHS [NS-12428] NR 42 TC 102 Z9 102 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1995 VL 96 IS 3 BP 1548 EP 1555 DI 10.1172/JCI118193 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RR853 UT WOS:A1995RR85300046 PM 7657825 ER PT J AU SMITH, CP LEE, WS MARTIAL, S KNEPPER, MA YOU, GF SANDS, JM HEDIGER, MA AF SMITH, CP LEE, WS MARTIAL, S KNEPPER, MA YOU, GF SANDS, JM HEDIGER, MA TI CLONING AND REGULATION OF EXPRESSION OF THE RAT-KIDNEY UREA TRANSPORTER (RUT2) SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE UREA; MEMBRANE TRANSPORT PROTEIN; NITROGEN METABOLISM; URINARY CONCENTRATING MECHANISM; COLON ID MEDULLARY COLLECTING DUCT; WATER CHANNEL; PROTEIN AB In mammals, urea is the predominant end-product of nitrogen metabolism and plays a central role in the urinary-concentrating mechanism. Urea accumulation in the renal medulla is critical to the ability of the kidney to concentrate urine to an osmolality greater than systemic plasma. Regulation of urea excretion and accumulation in the renal medulla depends on the functional state of specialized phloretin-sensitive urea transporters. To study these transporters and their regulation of expression we isolated a cDNA which encodes the rat homologue (rUT2) of rabbit UT2 (You, G., C. P. Smith, Y. Kanai, W.-S. Lee, M. Stelzner, and M. A. Hediger, et al. Nature (Lond.). 1993, 365:844-847). Rat UT2 has 88% amino acid sequence identity to rabbit UT2 and 64% identity to the recently cloned human erythrocyte urea transporter, HUT11 (Olives, B., P. Neav, P. Badly, M. A. Hediger, G. Rousselet, J. P. Cartron, and P. Ripoch J. Biol. Chem. 1994. 269:31649-31652). Analysis of rat kidney mRNA revealed two transcripts of size 2.9 and 4.0 kb which had spatially distinct distributions. Northern analysis and in situ hybridization showed that the 4.0-kb transcript was primarily responsive to changes in the protein content of the diet whereas the 2.9-kb transcript was responsive to changes in the hydration state of the animal. These studies reveal that the expression levels of the two rUT2 transcripts are modulated by different pathways to allow fluid and nitrogen balance to be regulated independently. Our data provide important insights into the regulation of the renal urea transporter UT2 and provide a basis on which to refine our understanding of the urinary concentrating mechanism and its regulation. C1 BRIGHAM & WOMENS HOSP,DEPT MED,DIV RENAL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. EMORY UNIV,SCH MED,DEPT MED,DIV RENAL,ATLANTA,GA 30322. NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. FU NIDDK NIH HHS [R29-DK41707, R01-DK45688, R01 DK041707, R01-DK707844] NR 39 TC 143 Z9 144 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1995 VL 96 IS 3 BP 1556 EP 1563 DI 10.1172/JCI118194 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RR853 UT WOS:A1995RR85300047 PM 7657826 ER PT J AU IKEWAKI, K NISHIWAKI, M SAKAMOTO, T ISHIKAWA, T FAIRWELL, T ZECH, LA NAGANO, M NAKAMURA, H BREWER, HB RADER, DJ AF IKEWAKI, K NISHIWAKI, M SAKAMOTO, T ISHIKAWA, T FAIRWELL, T ZECH, LA NAGANO, M NAKAMURA, H BREWER, HB RADER, DJ TI INCREASED CATABOLIC RATE OF LOW-DENSITY LIPOPROTEINS IN HUMANS WITH CHOLESTERYL ESTER TRANSFER PROTEIN-DEFICIENCY SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE CHOLESTERYL ESTER TRANSFER PROTEIN; KINETICS; STABLE ISOTOPES; LOW DENSITY LIPOPROTEINS; APOLIPOPROTEIN B ID APOLIPOPROTEIN-A-I; LIPID TRANSFER PROTEIN; MESSENGER-RNA LEVELS; FAMILIAL HYPERALPHALIPOPROTEINEMIA; PLASMA-LIPOPROTEINS; STABLE ISOTOPES; TRANSGENIC MICE; HEPG2 CELLS; RECEPTOR; SERUM AB The cholesteryl ester transfer protein (CETP) transfers lipids among lipoprotein particles and plays a central role in lipoprotein metabolism, Humans with genetic deficiency of CETP have both elevated HDL cholesterol and apolipoprotein A-I concentrations as well as decreased LDL cholesterol and apolipoprotein B levels, The present study was undertaken to elucidate the metabolic basis for the decreased LDL cholesterol and apo B levels in CETP deficiency, We conducted a series of in vivo apo B kinetic studies in two unrelated homozygotes with CETP deficiency and in control subjects. A primed constant infusion of stable isotopically labeled phenylalanine was administered to the two CETP deficient subjects and control subjects and apo B kinetic parameters in VLDL, intermediate density lipoproteins, and LDL were obtained by using a multicompartmental model, The fractional catabolic rates (FCR) of LDL apo B were significantly increased in the CETP-deficient subjects (0.56 and 0.75/d) compared with the controls (mean FCR of 0.39/d), Furthermore, the production rates of apo B in VLDL and intermediate density lipoprotein were decreased by 55% and 81%, respectively, in CETP deficiency compared with the controls, In conclusion, CETP-deficient subjects were demonstrated to have substantially increased catabolic rates of LDL apo B as the primary metabolic basis for the low plasma levels of LDL apo B, This result indicates that the LDL receptor pathway may be up-regulated in CETP deficiency. C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. JIKEI UNIV,AOTO HOSP,SCH MED,DEPT INTERNAL MED,TOKYO,JAPAN. RP IKEWAKI, K (reprint author), NATL DEF MED COLL,DEPT INTERNAL MED 1,3-2 NAMIKI,TOKOROZAWA,SAITAMA 359,JAPAN. NR 47 TC 71 Z9 71 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1995 VL 96 IS 3 BP 1573 EP 1581 DI 10.1172/JCI118196 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RR853 UT WOS:A1995RR85300049 PM 7657828 ER PT J AU KASHYAP, VS SANTAMARINAFOJO, S BROWN, DR PARROTT, CL APPLEBAUMBOWDEN, D MEYN, S TALLEY, G PAIGEN, B MAEDA, N BREWER, HB AF KASHYAP, VS SANTAMARINAFOJO, S BROWN, DR PARROTT, CL APPLEBAUMBOWDEN, D MEYN, S TALLEY, G PAIGEN, B MAEDA, N BREWER, HB TI APOLIPOPROTEIN-E DEFICIENCY IN MICE - GENE REPLACEMENT AND PREVENTION OF ATHEROSCLEROSIS USING ADENOVIRUS VECTORS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE APOLIPOPROTEIN E; GENE THERAPY; ATHEROGENESIS; IN VIVO; ADENOVIRIDAE ID DENSITY-LIPOPROTEIN RECEPTOR; FIREFLY LUCIFERASE GENE; III HYPERLIPOPROTEINEMIA; MEDIATED TRANSFER; MAMMALIAN-CELLS; MESSENGER-RNA; STEM-CELLS; EXPRESSION; MOUSE; DNA AB Apolipoprotein E (apoE)-deficient mice develop marked hyperlipidemia as well as atherosclerosis and thus are an excellent animal model for evaluating the potential for gene therapy in human genetic dyslipoproteinemias, Recombinant adenovirus containing either human apoE (rAdv.apoE) or the reporter gene luciferase (rAdv.luc) were generated and infused intravenously in apoE-deficient mice with preinfusion plasma total cholesterol of 644+/-149 mg/dl and cholesterol rich VLDL/IDL. After a single infusion of rAdv.apoE, plasma concentrations of human apoE ranging from 1.5 to 650 mg/dl were achieved, Adenovirus-mediated apoE replacement resulted in normalization of the lipid acid lipoprotein profile with markedly decreased total cholesterol (103+/-18 mg/dl), VLDL, IDL, and LDL, as well as increased HDL, Measurement of aortic atherosclerosis 1 mo after adenoviral infusion demonstrated a marked reduction in the mean lesion area of mice infused with rAdv.apoE (58+/-8 x 10(3) mu m(2)) when compared with control mice infused with rAdv.luc (161+/-19 x 10(3) mu m(2); P < 0.0001), Thus, apoE expression for 4 wk was sufficient to markedly reduce atherosclerosis, demonstrating the feasibility of gene therapy for correction of genetic hyperlipidemias resulting in atherosclerosis, The combined use of adenovirus vectors and the apoE-deficient mouse represents a new in vivo approach that will permit rapid screening of candidate genes for the prevention of atherosclerosis. C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. JACKSON LAB,BAR HARBOR,ME 04609. UNIV N CAROLINA,SCH MED,CHAPEL HILL,NC 27514. FU NHLBI NIH HHS [HL-32087] NR 57 TC 114 Z9 115 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1995 VL 96 IS 3 BP 1612 EP 1620 DI 10.1172/JCI118200 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RR853 UT WOS:A1995RR85300053 PM 7657831 ER PT J AU KADIISKA, MB BURKITT, MJ XIANG, QH MASON, RP AF KADIISKA, MB BURKITT, MJ XIANG, QH MASON, RP TI IRON SUPPLEMENTATION GENERATES HYDROXYL RADICAL IN-VIVO - AN ESR SPIN-TRAPPING INVESTIGATION SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Note DE FREE RADICAL; PBN; DMSO; IRON DIET; RATS ID LIPID-PEROXIDATION INVIVO; HEPATIC-FIBROSIS; FERRIC-COMPLEXES; OVERLOAD; HEMOCHROMATOSIS; SUPEROXIDE; CHELATORS; CITRATE; PATHOGENESIS; AUTOXIDATION AB Electron spin resonance (ESR) spectroscopy has been used to investigate hydroxyl radical generation in rats with chronic dietary iron loading, A secondary radical spin-trapping technique was used where hydroxyl radical forms methyl radical upon reaction with DMSO. The methyl radical was then detected by ESR spectroscopy as its adduct with the spin trap alpha-phenyl-N-t-butylnitrone (PBN). This adduct was detected in the bile of rats 10 wk after being fed an iron-loading diet and 40 min after the i.p. injection of the spin trap PBN dissolved in DMSO. Bile samples were collected into a solution of the ferrous stabilizing chelator 2,2'-dipyridyl in order to prevent the generation of radical adducts ex vivo during bile collection, Identification of the ESR spectrum of the major radical adduct as that of PBN/(CH3)-C-. provides evidence for the generation of the hydroxyl radical during iron supplementation. Desferal completely inhibited in vivo hydroxyl radical generation stimulated by high dietary iron intake, No radical adducts were detected in rats which were fed the control diet for the same period of time. This is the first evidence of hydroxyl radical generation in chronic iron-loaded rats. C1 ROWETT RES INST,BUCKSBURN AB2 95B,ABERDEEN,SCOTLAND. HUMAN MED UNIV,FAC PREVENT MED,DEPT HYG CHEM,CHANGSHA 410078,PEOPLES R CHINA. RP KADIISKA, MB (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 48 TC 97 Z9 98 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1995 VL 96 IS 3 BP 1653 EP 1657 DI 10.1172/JCI118205 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RR853 UT WOS:A1995RR85300058 PM 7657835 ER PT J AU BITTON, RJ FIGG, WD VENZON, DJ DALAKAS, MC BOWDEN, C HEADLEE, D REED, E MYERS, CE COOPER, MR AF BITTON, RJ FIGG, WD VENZON, DJ DALAKAS, MC BOWDEN, C HEADLEE, D REED, E MYERS, CE COOPER, MR TI PHARMACOLOGICAL VARIABLES ASSOCIATED WITH THE DEVELOPMENT OF NEUROLOGIC TOXICITY IN PATIENTS TREATED WITH SURAMIN SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article AB Purpose: To describe pharmacologic variables correlated with the development of neurologic toxicity in patients treated with suramin, Methods: Eighty-one patients were treated with suramin in a phase I study. The rate of drug infusion was continuously adjusted to maintain a preassigned plasma suramin concentration (175, 215, or 275 mu g/mL) for a fixed duration (2 to 8 weeks), Results: Eight patients developed grade III/IV neurologic motor impairment (predominantly motor axonal polyneuropathy). All were treated at the 275-mu g/mL concentration. One patient treated at the 215-mu g/mL concentration developed grade II motor dysfunction. In addition, seven of nine patients had sensory symptoms. pharmacologic variables associated with the development of polyneuropathy included total cumulative suramin dose, duration of exposure to plasma concentrations greater than 200 mu g/mL, and area under the curve (AUG) greater than 200 mu g/mL. Conclusion: Significant neurologic toxicity can result from therapy with suramin, even when dosing is designed to avoid exposure to plasma concentrations greater than 350 mu g/mL. Future clinical trials of suramin should be designed in such a way as to limit the total cumulative dose to less than or equal to 157 mg/kg given over a period of greater than or equal to 8 weeks, limit the period of exposure to plasma suramin concentrations greater than 200 mu g/mL to less than or equal to 25 days, and limit the AUC greater than 200 mu g/mL to less than or equal to 48,000 mg . h/L. C1 NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NINCDS,NEUROL DIS SECT,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008; Figg Sr, William/M-2411-2016 NR 12 TC 31 Z9 31 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP PY 1995 VL 13 IS 9 BP 2223 EP 2229 PG 7 WC Oncology SC Oncology GA RT917 UT WOS:A1995RT91700011 PM 7666080 ER PT J AU BROWMAN, GP BERGSAGEL, D SICHERI, D OREILLY, S WILSON, KS RUBIN, S BELCH, A SHUSTIK, C BARR, R WALKER, I JAMES, K ZEE, B JOHNSTON, D AF BROWMAN, GP BERGSAGEL, D SICHERI, D OREILLY, S WILSON, KS RUBIN, S BELCH, A SHUSTIK, C BARR, R WALKER, I JAMES, K ZEE, B JOHNSTON, D TI RANDOMIZED TRIAL OF INTERFERON MAINTENANCE IN MULTIPLE-MYELOMA - A STUDY OF THE NATIONAL-CANCER-INSTITUTE OF CANADA CLINICAL-TRIALS GROUP SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ONCOLOGY-GROUP; PREDNISONE; MELPHALAN; ALFA-2B; ALPHA AB Purpose: To determine whether interferon maintenance therapy improves overall survival and response duration in patients with multiple myeloma who have responded to induction therapy with melphalan and prednisone. Patients and Methods: in a multicenter trial, patients with symptomatic clinical stage land stage II and III multiple myeloma were registered at diagnosis and those who responded to melphalan-prednisone (MP)were randomized either to receive interferon (2 mU/m(2)) subcutaneously three times per week or no maintenance. MP was discontinued in both groups once a stable response plateau of the monoclonal protein was reached. Interferon was continued until relapse, and then was restarted on subsequent response to MP. Interferon toxicity was recorded using a self-report diary. Survival and response duration were calculated using life-table methods, and were adjusted in the analysis for imbalances in baseline prognostic factors. Results: Four hundred two patients were registered and 176 responders were randomized (85 to interferon and 91 to control), At a median follow-up time of 43 months, the median survival duration was 43 months for interferon and 35 months for control (P = .16), but when adjusted for chance imbalances in baseline prognostic factors (mainly performance status), the median survival duration was 44 months and 33 months for interferon and control, respectively (P = .049). Progression-free survival from randomization to first relapse also favored interferon (unadjusted P < .002; adjusted P < .003). Interferon toxicity caused 58% of patients to reduce their dose, of which 84% were able to return to the initial dose; 14% had to discontinue interferon treatment, Conclusion: Interferon maintenance therapy improves progression-free and overall survival of patients with multiple myeloma who respond to melphalan cmd prednisone. Toxicity is substantial and must be weighed by patients against the potential benefits in response duration and survival. (C) 1995 by American Society of Clinical Oncology. C1 QUEENS UNIV,CANADA CLIN TRIALS GRP,NCI,KINGSTON,ON,CANADA. OI Zee, Benny Chung-Ying/0000-0002-7238-845X NR 20 TC 85 Z9 87 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP PY 1995 VL 13 IS 9 BP 2354 EP 2360 PG 7 WC Oncology SC Oncology GA RT917 UT WOS:A1995RT91700028 PM 7666094 ER PT J AU CHESON, BD AF CHESON, BD TI INFECTIOUS AND IMMUNOSUPPRESSIVE COMPLICATIONS OF PURINE ANALOG THERAPY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID CHRONIC LYMPHOCYTIC-LEUKEMIA; HAIRY-CELL LEUKEMIA; PHASE-II TRIAL; NON-HODGKINS-LYMPHOMA; CONTINUOUS-INFUSION SCHEDULE; LOW-GRADE LYMPHOMA; ACUTE LYMPHOBLASTIC-LEUKEMIA; ADVANCED MYCOSIS-FUNGOIDES; LOW-DOSE DEOXYCOFORMYCIN; CANCER-STUDY-GROUP AB Purpose: The purine analogs fludarabine, cladribine, and pentostatin are active agents in the treatment of indolent lymphoid malignancies. This report reviews the pattern, severity, and consequences of the immunosuppression and myelotoxicity associated with these agents. Methods: The literature was searched using MedLine and Cancerline, as well as the bibliographies of published reports through the winter of 1994 and 1995. Results: Each of these drugs induces profound lymphocytopenia. A marked decrease in CD4 cells may persist for several years, while other mononuclear-cell populations recover more rapidly. The spectrum of infections encountered in these patients appears to be altered to include a wide range of opportunistic organisms. Factors that increase the risk of these infections include concurrent corticosteroids, extensive prior therapy, particularly with another purine analog, and poor response to purine analog treatment. Conclusion: Because of the frequency of life-threatening infections with unusual pathogens that may occur in patients treated with purine analogs, aggressive and early diagnostic evaluation and appropriate use of myeloid growth factors may be necessary to ensure appropriate antimicrobial therapy. RP CHESON, BD (reprint author), NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,CLIN INVEST BRANCH,EXECUT PLAZA N,ROOM 741,BETHESDA,MD 20892, USA. NR 183 TC 218 Z9 222 U1 0 U2 3 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 SEP PY 1995 VL 13 IS 9 BP 2431 EP 2448 PG 18 WC Oncology SC Oncology GA RT917 UT WOS:A1995RT91700038 PM 7666104 ER PT J AU PREUS, HR ANERUD, A BOYSEN, H DUNFORD, RG ZAMBON, JJ LOE, H AF PREUS, HR ANERUD, A BOYSEN, H DUNFORD, RG ZAMBON, JJ LOE, H TI THE NATURAL-HISTORY OF PERIODONTAL-DISEASE - THE CORRELATION OF SELECTED MICROBIOLOGICAL PARAMETERS WITH DISEASE SEVERITY IN SRI-LANKAN TEA WORKERS SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE DEVELOPING COUNTRIES; BACTERIOLOGY; PERIDONTITIS; GINGIVITIS; ACTINOBACILLUS ACTINOMYCETEMCOMITANS; PORPHYROMONAS GINGIVALIS; PREVOTELLA INTERMEDIA ID BLACK-PIGMENTED BACTEROIDES; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; JUVENILE PERIODONTITIS; ADULT PERIODONTITIS; SUBGINGIVAL PLAQUE; BREAKDOWN; IDENTIFICATION; MICROORGANISMS; TANZANIANS; KENYANS AB The purpose of this study was to assess the prevalence of A. actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia, and their association with periodontal disease states in a population sample from Sri Lanka. Based on clinical parameters, a total of 536 sites in 268 male Sri Lankan tea workers were categorized as healthy, or showing gingivitis only, moderate or advanced periodontitis. Bacterial samples were obtained from all sites and the three target bacteria identified by indirect immunofluorescence. P. intermedia, P. gingivalis and A. actinomycetemcomitans were found in 76%, 40% and 15% of the subjects, respectively. Of the 536 periodontal sites, 10.5% were categorized with ''no disease'', 14% ''gingivitis only''; 59% with moderate and 16% with advanced periodontitis. The prevalence of P. gingivalis and P. intermedia was significantly higher in sites with moderate and advanced periodontitis than in sites with no disease or gingivitis only. A. actinomycetemcomitans was not found in healthy sites, but occurred with equal frequency in sites with gingivitis. moderate and advanced periodontitis. The association between these three bacteria and periodontal diseases in Sri Lankan tea laborers was similar to that described for other non-industrialized and industrialized countries. C1 NIDR,BETHESDA,MD 20892. SUNY BUFFALO,SCH DENT MED,DEPT ORAL BIOL,BUFFALO,NY. RP PREUS, HR (reprint author), UNIV OSLO,FAC DENT,DEPT PERIODONTOL,GEITMYRSVN 71,N-0455 OSLO,NORWAY. NR 41 TC 39 Z9 39 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD SEP PY 1995 VL 22 IS 9 BP 674 EP 678 DI 10.1111/j.1600-051X.1995.tb00825.x PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA RQ391 UT WOS:A1995RQ39100003 PM 7593696 ER PT J AU PHILIBERT, RA RICHARDS, L LYNCH, CF WINOKUR, G AF PHILIBERT, RA RICHARDS, L LYNCH, CF WINOKUR, G TI EFFECT OF ECT ON MORTALITY AND CLINICAL OUTCOME IN GERIATRIC UNIPOLAR DEPRESSION SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 147th Annual Meeting of the American-Psychiatric-Association CY MAY 21-27, 1994 CL PHILADELPHIA, PA SP Amer Psychiat Assoc ID ELECTROCONVULSIVE-THERAPY; ANTIDEPRESSANTS AB Background: Recent reports have called into question the safety and effectiveness of electroconvulsive therapy (ECT). Method: To investigate these claims, the effects of ECT on clinical outcomes were examined as part of a retrospective, naturalistic study of 192 geriatric patients consecutively admitted between 1980 and 1987 to a large midwestern tertiary care center for the treat ment of depression. Data were analyzed by a variety of parametric and nonparametric methods including ANOVA and survival analysis. Results: Patients who received ECT (N = 108) were more likely to exhibit psychomotor retardation and to have had prior courses of ECT than those who did not receive ECT (N = 84), Furthermore, despite the absence of differences in the overall rate or severity of medical comorbidity, patients receiving ECT were more likely to be alive at follow-up and to demonstrate greater clinical improvement than those treated only with pharmacotherapy. Conclusion: These results confirm previous studies demonstrating the superior efficacy of ECT as compared with conventional pharmacotherapy treatment in patients hospitalized with depression and document its safety in long-term follow-up. C1 UNIV IOWA,COLL MED,DEPT PSYCHIAT,IOWA CITY,IA 52242. UNIV IOWA,COLL MED,DEPT PREVENT MED & ENVIRONM HLTH & PATHOL,IOWA CITY,IA 52242. RP PHILIBERT, RA (reprint author), NIMH,CLIN NEUROSCI BRANCH,BLDG 49,ROOM B1EE16,49 CONVENT RD,BETHESDA,MD 20892, USA. FU NIMH NIH HHS [T32MH-14620] NR 18 TC 49 Z9 49 U1 0 U2 0 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 SEP PY 1995 VL 56 IS 9 BP 390 EP 394 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA RV193 UT WOS:A1995RV19300001 PM 7665536 ER PT J AU ASCHER, JA COLE, JO COLIN, JN FEIGHNER, JP FERRIS, RM FIBIGER, HC GOLDEN, RN MARTIN, P POTTER, WZ RICHELSON, E SULSER, F AF ASCHER, JA COLE, JO COLIN, JN FEIGHNER, JP FERRIS, RM FIBIGER, HC GOLDEN, RN MARTIN, P POTTER, WZ RICHELSON, E SULSER, F TI BUPROPION - A REVIEW OF ITS MECHANISM OF ANTIDEPRESSANT ACTIVITY SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID ANTI-DEPRESSANT; DOPAMINE CONCENTRATIONS; MESOLIMBIC SYSTEM; NUCLEUS-ACCUMBENS; METABOLITES; RECEPTORS; STRIATUM; INVIVO; NOREPINEPHRINE; MICRODIALYSIS AB Background: The mechanism of action of the novel antidepressant bupropion remains unclear after many years of study. A review of the relevant biochemical, in vivo brain microdialysis, electrophysiologic, behavioral, and clinical data clarifies what is known about this unique compound and suggests possible modes of action. Method: A panel of 11 experts was convened for a conference to discuss bupropion's mechanism of antidepressant activity. Four of the panelists presented current research findings, followed by a discussion. Results: (1) Biochemical studies suggest down-regulation of postsynaptic beta-adrenoceptors and desensitization of the norepinephrine-stimulated adenylate cyclase in the rat cortex occur only after chronic administration of very high doses of bupropion. (2) In vivo brain microdialysis studies demonstrate that, after chronic administration, there is an enhancement of bupropion-induced increases in extracellular dopamine in the nucleus accumbens. (3) Electrophysiologic data show that with acute dosing, bupropion reduces the firing rates of noradrenergic neurons in the locus ceruleus, The firing rates of dopaminergic neurons are reduced by bupropion in the A9 and A10 areas of the brain, but only at very high doses, and bupropion does not alter the firing rates of serotonergic neurons in the dorsal raphe, (4) Behavioral studies show that the most active metabolite of bupropion, hydroxybupropion (306U73), appears to be responsible for a large part of the compound's effects in animal models of antidepressant activity. (5) Clinical studies indicate that bupropion enhances noradrenergic functional activity as reflected by an increased excretion of the hydroxy metabolite of melatonin, while at the same time producing a presumably compensatory decrease in norepinephrine turnover. In one study, bupropion elevated plasma levels of the dopamine metabolite homovanillic acid in nonresponders, but not in responders. Conclusion: The mechanism of action of bupropion appears to have an unusual, not fully understood, noradrenergic link. The bupropion metabolite hydroxybupropion probably plays a critical role in bupropion's antidepressant activity, which appears to be predominantly associated with long-term noradrenergic effects. The mild central nervous system activating effects of bupropion appear to be due to weak dopaminergic mechanisms. There is some evidence that dopamine may contribute to bupropion's antidepressant properties. Antidepressant effects of bupropion are not serotonergically mediated. C1 BURROUGHS WELLCOME CO,DEPT PSYCHIAT NEUROL,RES TRIANGLE PK,NC 27709. BURROUGHS WELLCOME CO,DIV PHARMACOL,RES TRIANGLE PK,NC 27709. MCLEAN HOSP,BELMONT,MA 02178. LABS WELLCOME,ISSY MOULINEAUX,FRANCE. FEIGHNER RES INST,SAN DIEGO,CA. UNIV BRITISH COLUMBIA,DIV NEUROL SCI,VANCOUVER,BC,CANADA. UNIV N CAROLINA,DEPT PSYCHIAT,CHAPEL HILL,NC. AMC RES GRP,BOULOGNE,FRANCE. NIMH,BETHESDA,MD 20892. MAYO CLIN,JACKSONVILLE,FL 32224. VANDERBILT UNIV,SCH MED,DEPT PHARMACOL & PSYCHIAT,NASHVILLE,TN 37212. RI Richelson, Elliott/A-9407-2012 NR 25 TC 485 Z9 494 U1 1 U2 27 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 SEP PY 1995 VL 56 IS 9 BP 395 EP 401 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA RV193 UT WOS:A1995RV19300002 PM 7665537 ER PT J AU JACOBSEN, FM AF JACOBSEN, FM TI RISPERIDONE IN THE TREATMENT OF AFFECTIVE-ILLNESS AND OBSESSIVE-COMPULSIVE DISORDER SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 148th Annual Meeting of the American-Psychiatric-Association CY MAY 20-25, 1995 CL MIAMI BEACH, FL SP Amer Psychiat Assoc ID CLOZAPINE; SCHIZOPHRENIA; SYMPTOMS AB Background: Risperidone is a new-generation atypical antipsychotic agent with potent dopaminergic and serotonergic antagonist activity. Compared with traditional dopamine-blocking neuroleptics, risperidone is more effective in treating negative symptoms of schizophrenia and may be less likely to cause extrapyramidal symptoms or tardive dyskinesia, Although risperidone is marketed for the treatment of schizophrenia, its novel psychopharmacologic effects and potentially mild side effect profile suggest the possibility of other therapeutic applications. An open prospective study was undertaken to determine whether risperidone might diminish psychosis, severe agitation, or rapid cycling in patients having acute and chronic primary affective illnesses (bipolar and major depressive disorder) and to document response characteristics and side effects, Additionally, a small number of patients with refractory obsessive-compulsive disorder (OCD) without comorbid tic or delusional disorders were given open trials of risperidone added to their medication. Method: Outpatients who fulfilled DSM-IV criteria for bipolar I, bipolar II, or major depressive disorder and suffered from psychosis or agitation associated with their illness (N = 20) and those who had treatment-refractory DSM-IV OCD (N = 5) were started on open trials of risperidone at daily doses of 1 to 1.5 mg. Doses were adjusted upwards to a maximum of 6 mg depending on clinical response. Results: Seventeen (85%) of 20 patients (13 bipolar, 4 major depressive disorder) showed complete or partial improvement after treatment with risperidone doses ranging from 1 to 6 mg/day (mean = 3.5 mg). Beneficial effects included decreases in agitation, psychosis, sleep disturbance, and rapid cycling. Four patients (20%) discontinued risperidone because of intolerable side effects. Five patients with refractory OCD also showed significant symptomatic improvement after the addition of risperidone. Conclusion: The findings suggest that (1) risperidone may be useful in the acute/p.r.n. and chronic treatment of psychosis, agitation, and cycling accompanying affective illness, and (2) risperidone may be useful in augmenting pharmacologic response in OCD. C1 NIMH,CLIN SCI LAB,WASHINGTON,DC. GEORGE WASHINGTON UNIV,SCH MED,DEPT PSYCHIAT,WASHINGTON,DC 20052. GEORGETOWN UNIV,SCH MED,WASHINGTON,DC 20057. RP JACOBSEN, FM (reprint author), TRANSCULTURAL MENTAL HLTH INST,1301 20TH ST NW,SUITE 711,WASHINGTON,DC 20036, USA. NR 26 TC 154 Z9 156 U1 2 U2 4 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 SEP PY 1995 VL 56 IS 9 BP 423 EP 429 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA RV193 UT WOS:A1995RV19300007 PM 7545159 ER PT J AU HELLER, J HERTZ, JA KJAER, TW RICHMOND, BJ AF HELLER, J HERTZ, JA KJAER, TW RICHMOND, BJ TI INFORMATION-FLOW AND TEMPORAL CODING IN PRIMATE PATTERN VISION SO JOURNAL OF COMPUTATIONAL NEUROSCIENCE LA English DT Article DE INFORMATION FLOW; SPIKE TIMING; NEURONAL CODES ID TWO-DIMENSIONAL PATTERNS; AFFERENT VISUAL SYSTEM; SINGLE UNITS; 2-DIMENSIONAL PATTERNS; EXTENDED APPLICATION; CORTEX; NEURONS; MEMORY; CAT AB We perform time-resolved calculations of the information transmitted about visual patterns by neurons in primary visual and inferior temporal cortices. All measurable information is carried in an effective time-varying firing rate, obtained by averaging the neuronal response with a resolution no finer than about 25 ms in primary visual cortex and around twice that in inferior temporal cortex. We found no better way for a neuron receiving these messages to decode them than simply to count spikes for this long. Most of the information tends to be concentrated in one or, more often, two brief packets, one at the very beginning of the response and the other typically 100 ms later. The first packet is the most informative part of the message, but the second one generally contains new information. A small but significant part of the total information in the message accumulates gradually over the entire course of the response. These findings impose strong constraints on the codes used by these neurons. C1 NIH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. HARVARD UNIV,DIV APPL SCI,CAMBRIDGE,MA 02138. NORDITA,DK-2100 COPENHAGEN,DENMARK. NR 22 TC 116 Z9 116 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0929-5313 J9 J COMPUT NEUROSCI JI J. Comput. Neurosci. PD SEP PY 1995 VL 2 IS 3 BP 175 EP 193 DI 10.1007/BF00961433 PG 19 WC Mathematical & Computational Biology; Neurosciences SC Mathematical & Computational Biology; Neurosciences & Neurology GA TD191 UT WOS:A1995TD19100001 PM 8521286 ER PT J AU WALLACE, FG JACOBS, L AF WALLACE, FG JACOBS, L TI RECOLLECTIONS ON DIAMOND,LOUIS,S SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Item About an Individual C1 NIH,PARASIT DIS LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC PROTOZOOLOGISTS PI POTOMAC PA 12263 GREENLEAF AVE, POTOMAC, MD 20854 SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD SEP-OCT PY 1995 VL 42 IS 5 BP 584 EP 585 DI 10.1111/j.1550-7408.1995.tb05910.x PG 2 WC Microbiology SC Microbiology GA RY385 UT WOS:A1995RY38500023 ER PT J AU DIAMOND, LS AF DIAMOND, LS TI CRYOPRESERVATION AND STORAGE OF PARASITIC PROTOZOA IN LIQUID-NITROGEN SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article DE CRITHIDIA; DIENTAMOEBA; ENTAMOEBA; GIARDIA; TRICHOMONADS; TRYPANOSOMA AB In 1961 I reported the first successful attempt to cryopreserve and store protozoa in liquid nitrogen. In this presentation, drawing on more than 30 years of personal experience, I discuss the factors which I consider to be most critical to the successful preservation and long term storage of several species of parasitic protozoa in liquid nitrogen. I then present my most successful protocol for cryopreservation of these parasites. Finally, I cite some longevity records for a variety of protozoa stored in liquid nitrogen vapor at the Laboratory of Parasitic Diseases. The oldest record is for a monoxenic culture of Entamoeba histolytica grown in association with Crithidia fasciculata that was frozen on January 6, 1961. Thirty-two years and 11 months later both parasites were recovered and used to initiate new culture lines. RP DIAMOND, LS (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. NR 20 TC 13 Z9 14 U1 0 U2 3 PU SOC PROTOZOOLOGISTS PI POTOMAC PA 12263 GREENLEAF AVE, POTOMAC, MD 20854 SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD SEP-OCT PY 1995 VL 42 IS 5 BP 585 EP 590 DI 10.1111/j.1550-7408.1995.tb05911.x PG 6 WC Microbiology SC Microbiology GA RY385 UT WOS:A1995RY38500024 ER PT J AU CLARK, CG AF CLARK, CG TI AXENIC CULTIVATION OF ENTAMOEBA-DISPAR BRUMPT 1925, ENTAMOEBA-INSOLITA GEIMAN AND WICHTERMAN 1937 AND ENTAMOEBA-RANARUM GRASSI 1879 SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article DE BACTERIA; CRITHIDIA FASCICULATA; ENTAMOEBA HISTOLYTICA; ESCHERICHIA COLI; FORMALIN; GASTRIC MUCIN; GLUTARALDEHYDE; TRYPANOSOMA CRUZI ID HISTOLYTICA AB Three species of Entamoeba have been grown in axenic culture for the first time. In two cases, never methods for adapting the organisms to growth without bacteria were employed. While E. ranarum was axenized by the classic technique of Diamond, from a monoxenic culture with Trypanosoma cruzi as the associate, both E. dispar and E. insolita were first grown in axenic culture medium supplemented with lethally irradiated bacteria. From there, E. insolita was axenized directly, but E. dispar initially required the presence of fixed bacteria. After prolonged culture under this technically axenic but unwieldy culture system, E. dispar was eventually adapted to growth in the absence of added bacteria. RP CLARK, CG (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,RM 126,BETHESDA,MD 20892, USA. RI Clark, C Graham/H-3683-2011 OI Clark, C Graham/0000-0002-0521-0977 NR 11 TC 39 Z9 40 U1 1 U2 4 PU SOC PROTOZOOLOGISTS PI POTOMAC PA 12263 GREENLEAF AVE, POTOMAC, MD 20854 SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD SEP-OCT PY 1995 VL 42 IS 5 BP 590 EP 593 DI 10.1111/j.1550-7408.1995.tb05912.x PG 4 WC Microbiology SC Microbiology GA RY385 UT WOS:A1995RY38500025 PM 7581333 ER PT J AU NASH, TE CONRAD, JT MOWATT, MR AF NASH, TE CONRAD, JT MOWATT, MR TI GIARDIA-LAMBLIA - IDENTIFICATION AND CHARACTERIZATION OF A VARIANT-SPECIFIC SURFACE PROTEIN GENE FAMILY SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article DE ANTIGENIC VARIATION; CYSTEIN-RICH PROTEINS; PROTOZOA; ZN FINGER PROTEINS ID CYSTEINE-RICH PROTEIN; ANTIGENIC VARIATION; MONOAMINE-OXIDASE; ZINC-BINDING; VARIABILITY; ISOLATE AB Giardia lamblia trophozoites undergo antigenic variation by modulating the expression of variant-specific surface proteins (VSP), which are encoded by a number of small multigene families. We characterized the genomic copy of the VSP gene expressed by the cloned trophozoite line H7, derived from the isolate GS/M, in addition to a related, but nonexpressed, family member. The coding regions of the two genes encode closely related polypeptides (86% identity). However, differences in the coding region of these genes reside solely in an 873 bp segment. Only four differences were found between the 5' flanking sequences (465 bp). The proximal 205 base pairs downstream from the coding regions were identical, but thereafter the sequences diverged (37% identity over the next 391 bp). Mapping studies indicated that no other VSP gene was located within 4 kb pairs of the expressed H7 VSP gene, and transcripts from the nonexpressed gene were detected in neither GS/H7 nor heterogeneous trophozoites populations derived from this cloned line. Any mechanisms responsible for the differential expression of VSP genes must reconcile the near identity of DNA sequences that flank the coding regions of expressed and nonexpressed VSP genes. RP NASH, TE (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,RM 126,BETHESDA,MD 20892, USA. NR 31 TC 27 Z9 27 U1 0 U2 0 PU SOC PROTOZOOLOGISTS PI POTOMAC PA 12263 GREENLEAF AVE, POTOMAC, MD 20854 SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD SEP-OCT PY 1995 VL 42 IS 5 BP 604 EP 609 DI 10.1111/j.1550-7408.1995.tb05914.x PG 6 WC Microbiology SC Microbiology GA RY385 UT WOS:A1995RY38500027 PM 7581335 ER PT J AU DVORAK, JA KOBAYASHI, S ALLING, DW HALLAHAN, CW AF DVORAK, JA KOBAYASHI, S ALLING, DW HALLAHAN, CW TI ELUCIDATION OF THE DNA SYNTHETIC CYCLE OF ENTAMOEBA SPP USING FLOW-CYTOMETRY AND MATHEMATICAL-MODELING SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article DE ENTAMOEBA HISTOLYTICA; ENTAMOEBA INVADENS; DNA SYNTHETIC CYCLE; FLOW CYTOMETRY; MATHEMATICAL MODELING ID AXENIC CULTIVATION; TRYPANOSOMA-CRUZI; BASE COMPOSITION; HISTOLYTICA; INVADENS; STRAINS; CELL AB We developed a method to study the DNA synthetic cycles of Entamoeba histolytica and Entamoeba invadens by flow cytometry (FCM) based on a preparative procedure to reduce both high levels of natural fluorescence and non-specific adsorption of fluorochromes. We modeled G(1), S, and G(2) phases as a series of overlapping Gaussian curves, Both E. histolytica and E. invadens displayed G(1), S, and G(2) proportions that are consistent with eukaryotic cell populations in exponential or stationary growth phase. Exponential phase E. histolytica populations contained a hypodiploid subset with a mass of about 20% less than the diploid value which we estimate by FCM to be 24 x 10(-14) g DNA/cell. Exponential phase E. invadens populations contained a hypodiploid subset with a mass of about 6% less than the diploid value which we estimate by FCM to be 30 x 10(-14) g DNA/cell. C1 KEIO UNIV,SCH MED,DEPT TROP MED & PARASITOL,SHINJUKU KU,TOKYO 160,JAPAN. NIAID,OFF SCI DIRECTOR,BETHESDA,MD 20892. RP DVORAK, JA (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. RI Kobayashi, seiki/L-4026-2013 NR 22 TC 24 Z9 24 U1 0 U2 0 PU SOC PROTOZOOLOGISTS PI POTOMAC PA 12263 GREENLEAF AVE, POTOMAC, MD 20854 SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD SEP-OCT PY 1995 VL 42 IS 5 BP 610 EP 616 DI 10.1111/j.1550-7408.1995.tb05915.x PG 7 WC Microbiology SC Microbiology GA RY385 UT WOS:A1995RY38500028 PM 7581336 ER PT J AU JOSHI, M DWYER, DM NAKHASI, HL AF JOSHI, M DWYER, DM NAKHASI, HL TI MOLECULAR-CLONING AND CHARACTERIZATION OF A LEISHMANIA-DONOVANI ALPHA-TUBULIN GENE SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article DE IMMUNOPRECIPITATION; IN VITRO AMASTIGOTE; NORTHERN BLOT; SOUTHERN BLOT; TUBULIN GENE ID PARASITIC PROTOZOAN; BETA-TUBULIN; DIFFERENTIATION; EXPRESSION; ENRIETTII; MEXICANA AB We have isolated a cDNA for an alpha-tubulin mRNA from L. donovani promastigotes and determined its complete nucleotide sequence. Both nucleotide and deduced amino acid sequence analysis of this cDNA showed significant similarity with a previously reported, partial sequence of an L. enriettii alpha-tubulin and the complete sequence of human alpha-tubulin. Further, the in vitro translated L. donovani alpha-tubulin gene product was specifically immunoprecipitated with a monoclonal antibody against human alpha-tubulin. Northern blot analysis revealed that there was little change in the expression of the L. donovani alpha-tubulin RNA during parasite differentiation from promastigote to the in vitro grown ''amastigote'' form. Southern blot analysis revealed a simple genomic organization for the L. donovani alpha-tubulin gene with more than one copy of the alpha-tubulin gene in the parasite genome. To our knowledge, this is the first complete sequence of an alpha-tubulin for Leishmania to be reported in the literature. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NIAID,PARASIT DIS LAB,CELL BIOL SECT,BETHESDA,MD 20892. NR 13 TC 12 Z9 12 U1 0 U2 0 PU SOC PROTOZOOLOGISTS PI POTOMAC PA 12263 GREENLEAF AVE, POTOMAC, MD 20854 SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD SEP-OCT PY 1995 VL 42 IS 5 BP 628 EP 632 DI 10.1111/j.1550-7408.1995.tb05918.x PG 5 WC Microbiology SC Microbiology GA RY385 UT WOS:A1995RY38500031 PM 7581339 ER PT J AU FLEURY, S THIBODEAU, J CROTEAU, G LABRECQUE, N ARONSON, HE CANTIN, C LONG, EO SEKALY, RP AF FLEURY, S THIBODEAU, J CROTEAU, G LABRECQUE, N ARONSON, HE CANTIN, C LONG, EO SEKALY, RP TI HLA-DR POLYMORPHISM AFFECTS THE INTERACTION WITH CD4 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CLASS-II MHC; BINDING-SITE; T-CELLS; ANTIGEN PRESENTATION; ALPHA-3 DOMAIN; LYMPHOCYTES-T; MOLECULES; BETA; PROTEIN; CHAIN AB Major histocompatibility complex (MHC) class II molecules are highly polymorphic and bind peptides for presentation to CD4(+) T cells. Functional and adhesion assays have shown that CD4 interacts with MHC class II molecules, leading to enhanced responses of CD4(+) T cells after the activation of the CD4-associated tyrosine kinase p56(lck). We have addressed the possible contribution of allelic polymorphism in the interaction between CD4 and MHC class II molecules. Using mouse DAP-3-transfected cells expressing different isotypes and allelic forms of the HLA-DR molecule, we have shown in a functional assay that a hierarchy exists in the ability of class II molecules to interact with CD4. Also, the study of DR4 subtypes minimized the potential contribution of polymorphic residues of the peptide-binding groove in the interaction with CD4. Chimeras between the DR4 or DR1 molecules, which interact efficiently with CD4, and DRw53, which interacts poorly, allowed the mapping of polymorphic residues between positions beta 180 and 189 that can exert a dramatic influence on the interaction with CD4. C1 INST RECH CLIN MONTREAL,IMMUNOL LAB,MONTREAL,PQ H2W 1R7,CANADA. UNIV MONTREAL,FAC MED,DEPT MICROBIOL & IMMUNOL,MONTREAL,PQ H2W 1R7,CANADA. NIAID,IMMUNOGENET LAB,ROCKVILLE,MD 20852. COLUMBIA UNIV,COLL PHYS & SURG,DEPT BIOCHEM & MOLEC BIOPHYS,NEW YORK,NY 10032. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 38 TC 30 Z9 31 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 1 PY 1995 VL 182 IS 3 BP 733 EP 741 DI 10.1084/jem.182.3.733 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA RQ754 UT WOS:A1995RQ75400011 PM 7650480 ER PT J AU JACKSON, SH GALLIN, JI HOLLAND, SM AF JACKSON, SH GALLIN, JI HOLLAND, SM TI THE P47(PHOX) MOUSE KNOCK-OUT MODEL OF CHRONIC GRANULOMATOUS-DISEASE SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID NEUTROPHIL CYTOCHROME-B; NADPH OXIDASE; CHROMOSOMAL LOCATION; LIGHT CHAIN; CLONING; GENE; MANIFESTATIONS; MACROPHAGES; EXPRESSION; CHILDHOOD AB Chronic granulomatous disease (CGD) is caused by a congenital defect in phagocyte reduced nicotinamide dinucleotide phosphate (NADPH) oxidase production of superoxide and related species. It is characterized by recurrent life-threatening bacterial and fungal infections and tissue granuloma formation. We have created a mouse model of CGD by targeted disruption of p47(phox), one of the genes in which mutations cause human CGD. Identical to the case in human CGD, leukocytes from p47(phox-/-) mice produced no superoxide and killed staphylococci ineffectively. p47(phox-/-) mice developed lethal infections and granulomatous inflammation similar to those encountered in human CGD patients. This model mirrors human CGD and confirms a critical role for the phagocyte NADPH oxidase in mammalian host defense. C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. NR 42 TC 359 Z9 362 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 1 PY 1995 VL 182 IS 3 BP 751 EP 758 DI 10.1084/jem.182.3.751 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA RQ754 UT WOS:A1995RQ75400013 PM 7650482 ER PT J AU KONIG, R SHEN, XL GERMAIN, RN AF KONIG, R SHEN, XL GERMAIN, RN TI INVOLVEMENT OF BOTH MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II ALPHA-CHAINS AND BETA-CHAINS IN CD4 FUNCTION INDICATES A ROLE FOR ORDERED OLIGOMERIZATION IN T-CELL ACTIVATION SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID SITE-DIRECTED MUTAGENESIS; MEDIATED GENE-TRANSFER; PROTEIN KINASE P56LCK; MHC CLASS-II; BINDING-SITE; SIGNAL TRANSDUCTION; ANTIGEN; RECEPTOR; REGION; MOLECULES AB CD4 is a membrane glycoprotein on T lymphocytes that binds to the same peptide:major histocompatibility complex (MHC) class II molecule recognized by the antigen-specific receptor (TCR), thereby stabilizing interactions between the TCR and peptide:MHC class II complexes and promoting the localization of the src family tyrosine kinase p56(lck) into the receptor complex. Previous studies identified a solvent-exposed loop on the class II beta 2 domain necessary for binding to CD4 and for eliciting CD4 coreceptor activity. Here, we demonstrate that a second surface-exposed segment of class II is also critical for CD4 function. This site is in the alpha 2 domain, positioned in single class II heterodimers in such a way that it cannot simultaneously interact with the same CD4 molecule as the beta 2 site. The ability of mutations at either site to diminish CD4 function therefore indicates that specifically organized CD4 and/or MHC class II oligomers play a critical role in coreceptor-dependent T cell activation. C1 NIAID,IMMUNOL LAB,LYMPHOCYTE BIOL SECT,BETHESDA,MD 20892. UNIV TEXAS,MED BRANCH,SEALY CTR MOLEC SCI,GALVESTON,TX 77555. UNIV TEXAS,MED BRANCH,DEPT MICROBIOL & IMMUNOL,GALVESTON,TX 77555. RI Konig, Rolf/B-3128-2008 NR 53 TC 100 Z9 100 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 1 PY 1995 VL 182 IS 3 BP 779 EP 787 DI 10.1084/jem.182.3.779 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA RQ754 UT WOS:A1995RQ75400016 PM 7650484 ER PT J AU SOUSA, CRE GERMAIN, RN AF SOUSA, CRE GERMAIN, RN TI MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I PRESENTATION OF PEPTIDES DERIVED FROM SOLUBLE EXOGENOUS ANTIGEN BY A SUBSET OF CELLS ENGAGED IN PHAGOCYTOSIS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TOXIC LYMPHOCYTES-T; PRESENTING CELLS; LANGERHANS CELLS; MACROPHAGES; MOLECULES; PROTEIN; SURFACE; RECOGNITION; EXPRESSION; LYSOSOMES AB Major histocompatibility complex (MHC) class I molecules generally present peptides derived from cytoplasmic proteins, but recent reports have suggested that macrophages (MO) may be uniquely able to present exogenous antigens via these molecules, and that particle-associated antigens show a marked increase in the efficiency of such presentation. We confirm here that particle uptake by MO permits exogenous ovaalbumin (OVA) to gain access to the endogenous class I processing pathway, an event that occurs rarely, if at all, in the absence of phagocytic stimuli. Presentation of soluble protein antigens by MHC class I molecules, however, is not limited to MCD, nor is direct coupling of antigen to the particle required. A variety of unconjugated particles promoted presentation of simultaneously offered soluble OVA to K-b-restricted T cells by both MO and non-MO antigen-presenting cells (APC), provided the latter could phagocytose the particles. Enhancement of presentation by phagocytic stimuli could not be explained by greater delivery of soluble antigen to endosomal compartments because such stimuli did not increase soluble tracer accumulation, nor did they improve presentation of OVA to an MHC class II-restricted T cell hybridoma. OVA presentation induced by cophagocytosis of particles and free antigen was nevertheless very inefficient in comparison to presentation of OVA peptide, and even modest responses required high concentrations of protein and particles. Furthermore, only a fraction of APC exposed to OVA and particles were lysed by anti-OVA cytotoxic T lymphocytes, despite virtually all cells showing OVA accumulation, particle uptake, and K-b expression. Titration experiments were most consistent with a model in which, by disrupting membrane integrity, phagocytic overload (''indigestion'') allows escape of OVA into the cytosol of some APC, rather than with a model in which phagocytosis activates a novel antigen processing pathway that has evolved to permit class I loading of exogenous antigen. These data suggest caution in the development of vaccine strategies based on use of particle conjugates for elicitation of CD8(+) T cell immunity, but, at the same time, may be relevant to understanding class I-restricted responses to some intracellular pathogens normally resident in membrane-bound vesicles. C1 NIAID,DIR,LBS,LI,BETHESDA,MD 20892. NR 44 TC 185 Z9 185 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 1 PY 1995 VL 182 IS 3 BP 841 EP 851 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA RQ754 UT WOS:A1995RQ75400022 ER PT J AU EVANS, VJ AF EVANS, VJ TI THE NICHD FAMILY AND CHILD WELL-BEING RESEARCH NETWORK - INTRODUCTION SO JOURNAL OF FAMILY ISSUES LA English DT Editorial Material RP EVANS, VJ (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBL INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0192-513X J9 J FAM ISSUES JI J. Fam. Issues PD SEP PY 1995 VL 16 IS 5 BP 517 EP 518 DI 10.1177/019251395016005001 PG 2 WC Family Studies SC Family Studies GA RT389 UT WOS:A1995RT38900001 ER PT J AU WELDON, PJ LETO, TL AF WELDON, PJ LETO, TL TI A COMPARATIVE-ANALYSIS OF PROTEINS IN THE SCENT GLAND SECRETIONS OF SNAKES SO JOURNAL OF HERPETOLOGY LA English DT Note C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. TEXAS A&M UNIV,DEPT BIOL,COLLEGE STN,TX 77843. SMITHSONIAN INST,CTR CONSERVAT & RES,FRONT ROYAL,VA 22630. NR 13 TC 4 Z9 5 U1 1 U2 2 PU SOC STUD AMPHIBIANS REPTILES PI OXFORD PA DEPT OF ZOOLOGY MIAMI UNIV, OXFORD, OH 45056 SN 0022-1511 J9 J HERPETOL JI J. Herpetol. PD SEP PY 1995 VL 29 IS 3 BP 474 EP 476 DI 10.2307/1565005 PG 3 WC Zoology SC Zoology GA TA491 UT WOS:A1995TA49100025 ER PT J AU DENG, YP BENNINK, JR KANG, HC HAUGLAND, RP YEWDELL, JW AF DENG, YP BENNINK, JR KANG, HC HAUGLAND, RP YEWDELL, JW TI FLUORESCENT CONJUGATES OF BREFELDIN-A SELECTIVELY STAIN THE ENDOPLASMIC-RETICULUM AND GOLGI-COMPLEX OF LIVING CELLS SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE BREFELDIN A, CONFOCAL MICROSCOPY; ENDOPLASMIC RETICULUM; FLUORESCENCE MICROSCOPY; GOLGI COMPLEX; MEMBRANE; VESICULAR TRANSPORT ID ORGANELLE STRUCTURE; CERAMIDE ANALOG; APPARATUS; PROTEINS; REDISTRIBUTION; ACCUMULATION; ENDOSOMES; SURFACE AB The fungal metabolite brefeldin A (BFA) interferes with vesicular trafficking in most animal cells, To gain insight into the mechanism of BFA action, we esterified it to the fluorophore, boron dipyromethene difluoride (BODIPY). BODIPY-BFA localized predominantly in the endoplasmic reticulum (ER) and Golgi complex of viable cells and was extracted by detergent treatment, suggesting it interacts primarily with lipid bilayers, The localization of the conjugate is conferred by BFA, since free BODIPY or BODIPY esterified to cyclopentanol did not specifically localize to internal membranes, BODIPY-BFA exhibited a similar biological activity to BFA, but only when used at higher concentrations and after a delay. HPLC analysis revealed that over this period, cells converted BODIPY-BFA to species co-eluting with free BODIPY and BFA, Therefore, BODIPY-BFA is probably inactive until BFA is released by cellular esterases, The specific localization of BODIPY-BFA to the ER and Golgi complex suggests that BFA might exert its effects on vesicular trafficking by perturbing the lipid bilayer of its target organelles, Because BODIPY-BFA intensely stains the ER at concentrations that have no discernible effects on intracellular transport or other cellular functions, it should be useful for visualizing the ER in living cells. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. MOLEC PROBES,EUGENE,OR. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 22 TC 37 Z9 37 U1 1 U2 2 PU HISTOCHEMICAL SOC INC PI NEW YORK PA MT SINAI MEDICAL CENTER 19 EAST 98TH ST SUTIE 9G, NEW YORK, NY 10029 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD SEP PY 1995 VL 43 IS 9 BP 907 EP 915 PG 9 WC Cell Biology SC Cell Biology GA RP287 UT WOS:A1995RP28700007 PM 7543914 ER PT J AU STEVENSON, MM TAM, MF WOLF, SF SHER, A AF STEVENSON, MM TAM, MF WOLF, SF SHER, A TI IL-12-INDUCED PROTECTION AGAINST BLOOD-STAGE PLASMODIUM-CHABAUDI AS REQUIRES IFN-GAMMA AND TNF-ALPHA AND OCCURS VIA A NITRIC OXIDE-DEPENDENT MECHANISM SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; CD4+ T-CELLS; SUSCEPTIBLE A/J MICE; NATURAL-KILLER-CELLS; INTERFERON-GAMMA; LISTERIA-MONOCYTOGENES; MACROPHAGE ACTIVATION; LEISHMANIA-MAJOR; IMMUNE-RESPONSE; MURINE MALARIA AB The effects of IL-12 administration on the development of protective immunity to blood-stage Plasmodium chabaudi AS were analyzed. Treatment of susceptible A/J mice on the day of infection and for 5 days postinfection with various doses (0.025-0.3 mu g) of rIL-12 significantly decreased the peak parasitemia level, but only treatment with 0.1 mu g resulted in increased survival. Treatment of resistant B6 mice with 0.1 mu g of rIL-12 using the same regimen also significantly decreased the peak parasitemia level, but 40% of the animals died. Treatment of these mice with anti-IL-12 mAb resulted in a more severe course of infection, but survival was not significantly altered. The mechanism of IL-12-induced resistance was examined in A/J mice during infection. Compared with spleen cells from untreated mice, cells from IL-12-treated mice produced significantly higher levels of IFN-gamma spontaneously as well as in response to Con A or Ag stimulation on day 7 postinfection. Significantly higher levels of IFN-gamma and TNF-alpha were found in the sera of IL-12-treated mice, which correlated with high levels of the nitric oxide (NO) metabolite, NO3-. Furthermore, CD4(+) T cell depletion was found to abrogate IL-12-induced resistance. Administration of neutralizing mAb against IFN-gamma or TNF-alpha to IL-12-treated mice showed that simultaneous depletion of both cytokines resulted in 100% mortality. The role of NO was investigated by administration of aminoguanidine, a selective inhibitor of cytokine-inducible nitric oxide synthase, to IL-12-treated mice. Significantly increased mortality was observed following treatment twice daily with 9 mg of aminoguanidine, but there was no effect on parasitemia. In conclusion, these results demonstrate that IL-12 regulates the development of resistance to P. chabaudi AS via a CD4(+) Th1 response, which involves the cytokines IFN-gamma and TNF-alpha, and is in part NO dependent. Therefore, IL-12, given in the appropriate dose, may be useful in the induction of protective immunity to blood-stage malaria. C1 MCGILL UNIV,CTR STUDY HOST RESISTANCE,MONTREAL,PQ,CANADA. GENET INST INC,CAMBRIDGE,MA 02140. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. RP STEVENSON, MM (reprint author), MONTREAL GEN HOSP,RES INST,1650 CEDAR AVE,MONTREAL,PQ H3G 1A4,CANADA. FU NIAID NIH HHS [R01-AI35955-01] NR 51 TC 257 Z9 266 U1 1 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1995 VL 155 IS 5 BP 2545 EP 2556 PG 12 WC Immunology SC Immunology GA RP743 UT WOS:A1995RP74300027 PM 7650384 ER PT J AU YOUN, BS JANG, IK BROXMEYER, HE COOPER, S JENKINS, NA GILBERT, DJ COPELAND, NG ELICK, TA FRASER, MJ KWON, BS AF YOUN, BS JANG, IK BROXMEYER, HE COOPER, S JENKINS, NA GILBERT, DJ COPELAND, NG ELICK, TA FRASER, MJ KWON, BS TI A NOVEL CHEMOKINE, MACROPHAGE INFLAMMATORY PROTEIN-RELATED PROTEIN-2 INHIBITS COLONY FORMATION OF BONE-MARROW MYELOID PROGENITORS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MOUSE CHROMOSOME-11; PROLIFERATION; LINKAGE; FAMILY; CELLS; GENES; IDENTIFICATION; MIP-1-ALPHA; EXPRESSION; RECEPTORS AB A new member of the beta-chemokine family, macrophage inflammatory protein (MIP)-related protein-2 (MRP-2) was isolated from a murine macrophage cell line, RAW 264.7. MRP-2 is composed of 122 amino acids of which the first 21 residues constitute a putative signal sequence. The putative mature protein is composed of 101 amino acids with a molecular weight of 11,600. MRP-2 is structurally similar to MIP-related protein-1 (MRP-1) (C10) and MIP-1 alpha. MRP-2 shows a 50.8% sequence identity at the protein level to MRP-1 and a 46.3% identity to MIP-1 alpha. MRP-2 detects approximately 1.3 kilobase mRNA from monocyte and macrophage cell lines but does not detect the mRNA from T and B cells. The MRP-2 gene termed Scya9 was mapped to the central region of mouse chromosome 11 near the Scya1 and Scya2 genes, which are also members of the beta-chemokine superfamily. The Scya gene cluster was located between neurofibromatosis type 1 (Nf1) and myeloperoxidase (Mpo). rMRP-2 significantly suppressed colony formation by murine and human bone marrow granulocyte-macrophage (CFU-granulocyte-macrophage), erythroid (burst-forming unit-E), and multipotential (CFU-granulocyte-erythroid-macrophage-megakaryocyte) progenitor cells stimulated by combinations of growth factors. C1 INDIANA UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,WALTHER ONCOL CTR,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,DEPT MED,INDIANAPOLIS,IN 46202. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. UNIV NOTRE DAME,DEPT BIOL SCI,NOTRE DAME,IN 46556. RI Fraser, Malcolm/C-9100-2009 FU NIAID NIH HHS [R01 AI-28175]; NIAMS NIH HHS [AR-40248]; NIDCR NIH HHS [R03 DE-10525] NR 32 TC 52 Z9 53 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1995 VL 155 IS 5 BP 2661 EP 2667 PG 7 WC Immunology SC Immunology GA RP743 UT WOS:A1995RP74300040 PM 7650394 ER PT J AU STEWART, DM NOTARANGELO, LD KURMAN, CC STAUDT, LM NELSON, DL AF STEWART, DM NOTARANGELO, LD KURMAN, CC STAUDT, LM NELSON, DL TI MOLECULAR-GENETIC ANALYSIS OF X-LINKED HYPOGAMMAGLOBULINEMIA AND ISOLATED GROWTH-HORMONE DEFICIENCY SO JOURNAL OF IMMUNOLOGY LA English DT Article ID AGAMMAGLOBULINEMIA; CELLS AB In 1980 the clinical syndrome of X-linked hypogammaglobulinemia and isolated growth hormone deficiency (XLA/GHD) was described. XLA/GHD patients have reduced serum levels of Ig and normal cell-mediated immunity, and thus resemble patients with Bruton's X-linked agammaglobulinemia (XLA). However, XLA/GHD patients also have isolated GHD. Mutations and deletions in the Bruton's tyrosine kinase gene (BTK) are responsible for Bruton's XLA. We investigated BTK gene expression in an XLA/GHD patient from the family originally described by Northern analysis, cDNA sequencing, and Western analysis of protein production using mAb to BTK. BTK mRNA was normal in size and abundance, and the mRNA sequence was normal over the coding region, except for a single silent mutation. BTK protein was present in normal amounts in PBMC of this patient. Thus, at the molecular level, XLA/GHD is a different disease entity from Bruton's XLA. These results suggest that undescribed genes critical for B cell development and growth hormone production exist on the X chromosome. C1 NCI,METAB BRANCH,IMMUNOPHYSIOL SECT,BETHESDA,MD 20892. UNIV BRESCIA,DEPT PEDIAT,BRESCIA,ITALY. RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 NR 18 TC 18 Z9 20 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1995 VL 155 IS 5 BP 2770 EP 2774 PG 5 WC Immunology SC Immunology GA RP743 UT WOS:A1995RP74300053 PM 7650402 ER PT J AU CLEMANS, DL KOLENBRANDER, PE AF CLEMANS, DL KOLENBRANDER, PE TI ISOLATION AND CHARACTERIZATION OF COAGGREGATION-DEFECTIVE (COG(-)) MUTANTS OF STREPTOCOCCUS-GORDONII DL1 (CHALLIS) SO JOURNAL OF INDUSTRIAL MICROBIOLOGY LA English DT Article DE COAGGREGATION-DEFECTIVE MUTANTS; ACCRETION; ORAL STREPTOCOCCI; ORAL BIOFILMS; ADHESINS ID ORAL BACTERIA; SANGUIS; SURFACE; POLYSACCHARIDE; COLONIZATION; STRAINS AB Streptococcus gordonii DL1 (Challis) bears coaggregation-mediating surface adhesins which recognize galactoside-containing surface polysaccharides on Streptococcus oralis 34, Streptococcus oralis C104, and Streptococcus SM PK509. Fifty-nine spontaneously-occurring coaggregation-defective (Cog(-)) mutants of S. gordonii DL1 unable to coaggregate with partner streptococci were isolated. Six representative Cog(-) mutants were characterized by their coaggregation properties with four Actinomyces naeslundii strains (T14V, PK947, PK606, PK984), Veillonella atypica PK1910, and Propionibacterium acnes PK93. The six representative Cog(-) mutants showed altered coaggregation with their streptococcal partners, A. naeslundii PK947, and P. acnes PK93. Based on the coaggregation phenotypes of these mutants, a model for the lactose-inhibitable coaggregation between S. gordonii DL1 and its partner bacteria is proposed. The potential use of these mutants in studies of oral biofilms is discussed. C1 NIDR,MICROBIAL ECOL LAB,BETHESDA,MD 20892. NR 20 TC 8 Z9 8 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0169-4146 J9 J IND MICROBIOL JI J. Indust. Microbiol. PD SEP PY 1995 VL 15 IS 3 BP 193 EP 197 DI 10.1007/BF01569825 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA TA263 UT WOS:A1995TA26300011 PM 8519477 ER PT J AU QUINN, TC JABS, DA HOLBROOK, JT HARDY, WD POLSKY, B LEWIS, RA CLOGSTON, P FAINSTEIN, V GROSS, R SAMO, T TUTTLE, C APUZZO, L BARTLETT, J DUNN, JP ELDRED, L FEINBERG, J FLYNN, T KING, R BARRON, B GREENSPAN, D LECOUNT, C PEYMAN, G FRANKLIN, R HEINEMANN, M SQUIRES, K WISECAMPBELL, S FRIEDMAN, AH CHEUNG, TW JUSTIN, N TEICH, SA SACKS, H SEVERIN, C FRIEDBERG, DN ADDESSI, A DIETERICH, D LAFLEUR, F WEINBERG, D JAMPOL, L MURPHY, R NAUGHTON, K HENDERLY, D HOLLAND, GN CHAFEY, S FALL, H KIMBRELL, C MACARTHUR, LJ FREEMAN, WR MEIXNERT, L PETERSON, TJ QUICENO, JI RICKMAN, L SIMANELLO, MA SPECTOR, S ODONNELL, J HOFFMAN, J IRVINE, A JACOBSON, M LARSON, J SEIFF, S WARNER, L DAVIS, J CHUANG, E ESPINAL, M MENDEZ, P CHEESEMAN, SH GITTINGER, J HAUBRICH, R KACHADOORIAN, H TOLSON, K BROWNBELLAMY, J KLEMM, AC MARKOWITZ, JA MEINERT, CL AMENDLIBERCCI, A COLESON, L COLLINS, KL COLLISON, BJ DODGE, J DONITHAN, M EWING, C FINK, N GERCZAK, C ISAACSON, MR KAPLANGILIPIN, A HUFFMAN, R LEVINE, CR NOWAKOWSKI, DJ SMITH, M TONASCIA, J VANNATTA, ML AGRESSEGAL, M ARMSTRONG, J BROTHERS, R HUBBARD, L HURLBURT, D MAGLI, Y MINER, K THOMAS, S VANDERHOOFYOUNG, M STEWART, G HUGHES, R LEEF, J PALMER, S MOWERY, R ELLENBERG, S KORVICK, J DAVIS, MD CLARK, T MERIN, L SATTLER, F JORDAN, C MILLS, J BROWN, BW CONWAY, B GRIZZLE, J NUSSENBLATT, R PHAIR, J SMITH, H KLINE, R MOSS, M CARELLA, A AF QUINN, TC JABS, DA HOLBROOK, JT HARDY, WD POLSKY, B LEWIS, RA CLOGSTON, P FAINSTEIN, V GROSS, R SAMO, T TUTTLE, C APUZZO, L BARTLETT, J DUNN, JP ELDRED, L FEINBERG, J FLYNN, T KING, R BARRON, B GREENSPAN, D LECOUNT, C PEYMAN, G FRANKLIN, R HEINEMANN, M SQUIRES, K WISECAMPBELL, S FRIEDMAN, AH CHEUNG, TW JUSTIN, N TEICH, SA SACKS, H SEVERIN, C FRIEDBERG, DN ADDESSI, A DIETERICH, D LAFLEUR, F WEINBERG, D JAMPOL, L MURPHY, R NAUGHTON, K HENDERLY, D HOLLAND, GN CHAFEY, S FALL, H KIMBRELL, C MACARTHUR, LJ FREEMAN, WR MEIXNERT, L PETERSON, TJ QUICENO, JI RICKMAN, L SIMANELLO, MA SPECTOR, S ODONNELL, J HOFFMAN, J IRVINE, A JACOBSON, M LARSON, J SEIFF, S WARNER, L DAVIS, J CHUANG, E ESPINAL, M MENDEZ, P CHEESEMAN, SH GITTINGER, J HAUBRICH, R KACHADOORIAN, H TOLSON, K BROWNBELLAMY, J KLEMM, AC MARKOWITZ, JA MEINERT, CL AMENDLIBERCCI, A COLESON, L COLLINS, KL COLLISON, BJ DODGE, J DONITHAN, M EWING, C FINK, N GERCZAK, C ISAACSON, MR KAPLANGILIPIN, A HUFFMAN, R LEVINE, CR NOWAKOWSKI, DJ SMITH, M TONASCIA, J VANNATTA, ML AGRESSEGAL, M ARMSTRONG, J BROTHERS, R HUBBARD, L HURLBURT, D MAGLI, Y MINER, K THOMAS, S VANDERHOOFYOUNG, M STEWART, G HUGHES, R LEEF, J PALMER, S MOWERY, R ELLENBERG, S KORVICK, J DAVIS, MD CLARK, T MERIN, L SATTLER, F JORDAN, C MILLS, J BROWN, BW CONWAY, B GRIZZLE, J NUSSENBLATT, R PHAIR, J SMITH, H KLINE, R MOSS, M CARELLA, A TI ANTIVIRAL EFFECTS OF FOSCARNET AND GANCICLOVIR THERAPY ON HUMAN-IMMUNODEFICIENCY-VIRUS P24 ANTIGEN IN PATIENTS WITH AIDS AND CYTOMEGALOVIRUS RETINITIS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNE-DEFICIENCY-SYNDROME; REPLICATION INVITRO; ACID DISSOCIATION; PHOSPHONOFORMATE FOSCARNET; CONTROLLED TRIAL; ZIDOVUDINE; INFECTION; DISEASE; TYPE-1; HIV AB To examine whether the prolonged survival seen in patients treated with foscarnet compared with those treated with ganciclovir was due to a direct effect on human immunodeficiency virus (HIV) replication, HIV p24 antigen was measured. Of 71 receiving foscarnet, 54% were p24 antigen-positive at enrollment (vs. 44% of 79 receiving ganciclovir). By immune complex-dissociated (ICD) p24 antigen analysis, 87% and 78%, respectively, were positive. After 1 month of treatment, there was a significant decline in standard (mean decline, 10.1 pg/mL) and ICD (mean, 39.6 pg/mL) p24 antigen in both groups (P = .0001). Mortality was greater in those who were ICD p24 antigen-positive than in those -negative at baseline (P = .03) and in subjects with an increase in ICD p24 antigen than in those with a decline (P = .09). Thus, each drug had a suppressive effect on circulating p24 antigen, which was predictive of improved survival. The inhibitory effect on CMV replication may have a beneficial effect on limiting HIV replication. C1 NIAID,BALTIMORE,MD 21205. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. CORNELL MED CTR,NEW YORK,NY. BAYLOR COLL MED,CULLEN EYE INST,HOUSTON,TX 77030. LOUISIANA STATE UNIV,MED CTR,NEW ORLEANS,LA. CORNELL UNIV,NEW YORK HOSP,MED CTR,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. MT SINAI SCH MED,NEW YORK,NY. NYU,MED CTR,NEW YORK,NY. NORTHWESTERN UNIV,CHICAGO,IL. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. USN HOSP,BETHESDA,MD 20814. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. UNIV MIAMI,SCH MED,MIAMI,FL. UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA. JOHNS HOPKINS UNIV,CTR COORDINATOR,SCH HYG & PUBL HLTH,BALTIMORE,MD 21218. UNIV WISCONSIN,FUNDUS PHOTOGRAPH READING CTR,MADISON,WI. ERC BIOSERV CORP,CTR DRUG DISTRIBUT,ROCKVILLE,MD. BIOMED RES INST,SERUM & CMV CULTURE REPOSITORY,ROCKVILLE,MD 20852. NEI,BETHESDA,MD. NIAID,BETHESDA,MD. RP QUINN, TC (reprint author), JOHNS HOPKINS UNIV,SCH MED,550 BLDG,SUITE 700,BALTIMORE,MD 21205, USA. NR 53 TC 12 Z9 12 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 SEP PY 1995 VL 172 IS 3 BP 613 EP 621 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RR073 UT WOS:A1995RR07300001 ER PT J AU SEI, S SAITO, K STEWART, SK CROWLEY, JS BROUWERS, P KLEINER, DE KATZ, DA PIZZO, PA HEYES, MP AF SEI, S SAITO, K STEWART, SK CROWLEY, JS BROUWERS, P KLEINER, DE KATZ, DA PIZZO, PA HEYES, MP TI INCREASED HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) TYPE-1 DNA CONTENT AND QUINOLINIC ACID CONCENTRATION IN BRAIN-TISSUES FROM PATIENTS WITH HIV ENCEPHALOPATHY SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNE-DEFICIENCY SYNDROME; CENTRAL-NERVOUS-SYSTEM; AIDS DEMENTIA COMPLEX; KYNURENINE PATHWAY METABOLISM; BLOOD MONONUCLEAR-CELLS; TUMOR-NECROSIS-FACTOR; REVERSE-TRANSCRIPTASE; CEREBROSPINAL-FLUID; III INFECTION; NEUROLOGICAL COMPLICATIONS AB Levels of human immunodeficiency virus type 1 (HIV-1) DNA and quinolinic acid were examined in areas of the central nervous system (CNS) and lymphoid organs (LN) from 5 AIDS patients with no clinically apparent CNS compromise (group I), 7 with CNS opportunistic diseases (group II), and 8 with HIV encephalopathy (group III). The brains from patients with HIV encephalopathy not only contained higher levels of HIV-1 DNA (cerebrum, P < .01; cerebellum, P < .05) as assessed by quantitative polymerase chain reaction but also showed a higher rate of viral pol region mutations suggestive of zidovudine or didanosine resistance than brains from patients in group I or II (P < .01). CNS quinolinic acid concentrations were significantly higher in group II and III patients than in group I (P = .03), even though quinolinic acid levels in LN were comparable among the 3 groups. These data suggest that CNS inflammatory changes associated with HIV encephalopathy may be triggered by a local productive HIV-1 infection within the CNS. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NINCDS,OFF CLIN DIRECTOR,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,BETHESDA,MD 20892. RP SEI, S (reprint author), NCI,PEDIAT BRANCH,BLDG 10,ROOM 13N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Kleiner, David/0000-0003-3442-4453 NR 53 TC 50 Z9 50 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 SEP PY 1995 VL 172 IS 3 BP 638 EP 647 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RR073 UT WOS:A1995RR07300004 PM 7658054 ER PT J AU OPERSKALSKI, EA STRAM, DO LEE, H ZHOU, Y DONEGAN, E BUSCH, MP STEVENS, CE SCHIFF, ER DIETRICH, SL MOSLEY, JW AF OPERSKALSKI, EA STRAM, DO LEE, H ZHOU, Y DONEGAN, E BUSCH, MP STEVENS, CE SCHIFF, ER DIETRICH, SL MOSLEY, JW TI HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION - RELATIONSHIP OF RISK GROUP AND AGE TO RATE OF PROGRESSION TO AIDS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CONGENITAL CLOTTING DISORDERS; INTRAVENOUS-DRUG-USERS; HTLV-III; NATURAL-HISTORY; TRANSFUSION SAFETY; BLOOD-TRANSFUSION; FACTOR-VIII; INCUBATION PERIOD; HOMOSEXUAL MEN; BISEXUAL MEN AB Age differences among risk groups may account for rate differences in progression of human immunodeficiency virus type 1 (HIV-1) infection to AIDS. Institutions in 6 US cities used a common protocol to study infected homosexual blood donors, recipients of blood components, and factor VIII-treated hemophiliacs. Follow-up was every 6 months. Actuarial risk for AIDS 8 years after infection was 51% among blood recipients, 36% among homosexual donors, and 24% among hemophiliacs. Significant risk group differences were explained by age differences among cohorts (medians of 61, 29, and 22 years, respectively). When age was adjusted for and both CD4 cell value and zidovudine treatment were used as time-dependent covariates, homosexual donors had more rapid progression than the other groups. Omitting Kaposi's sarcoma as an AIDS-defining condition removed any significant differences among risk groups except CD4 cell count and age. Thus, major factors in AIDS progression are age-related. C1 UNIV SO CALIF,SCH MED,TRANSFUS SAFETY STUDY,LOS ANGELES,CA 90032. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. HUNTINGTON MEM HOSP,HEMOPHILIA CLIN,PASADENA,CA. WAYNE STATE UNIV,DETROIT,MI. UNIV MIAMI,MIAMI,FL. AMER RED CROSS,BLOOD SERV,MIAMI,FL. MT SINAI MED CTR,NEW YORK,NY. CORNELL UNIV,MED CTR,NEW YORK,NY 10021. NEW YORK BLOOD CTR,NEW YORK,NY 10021. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA. IRWIN MEM BLOOD CTR,SAN FRANCISCO,CA. ALTA BATES COMMUNITY HOSP,OAKLAND,CA. PUGET SOUND BLOOD CTR,SEATTLE,WA. NHLBI,BETHESDA,MD. FU NHLBI NIH HHS [HB-4-7003, HB-4-7002, HB-9-7074] NR 61 TC 78 Z9 80 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 SEP PY 1995 VL 172 IS 3 BP 648 EP 655 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RR073 UT WOS:A1995RR07300005 PM 7658055 ER PT J AU FEITELSON, MA DUAN, LX GUO, J SUN, B WOO, J STEENSMA, K HORIIKE, N BLUMBERG, BS AF FEITELSON, MA DUAN, LX GUO, J SUN, B WOO, J STEENSMA, K HORIIKE, N BLUMBERG, BS TI X-REGION DELETION VARIANTS OF HEPATITIS-B VIRUS IN SURFACE ANTIGEN-NEGATIVE INFECTIONS AND NON-A, NON-B-HEPATITIS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID POLYMERASE CHAIN-REACTION; HEPATOCELLULAR-CARCINOMA; C VIRUS; POSTTRANSFUSION HEPATITIS; CORE ANTIGEN; VIRAL REPLICATION; ESCHERICHIA-COLI; GENE PRODUCT(S); BLOOD-DONORS; ANTIBODY AB The etiology of non-A, non-B hepatitis (NANBH) in renal dialysis patients was determined. Hepatitis C virus was present in many, but its appearance did not correlate with elevated alanine aminotransaminase. When sera from these patients were tested for antibodies against hepatitis B virus (HBV) X antigen and polymerase, 70% were positive. HBV infection was confirmed by polymerase chain reaction using several HBV-specific primer pairs. However, amplification with X region primers failed to yield products in many patients. Cloning and sequencing of these products demonstrated deletions within the X region. Hence, X-deletion variants of HBV are strongly associated with NANBH in renal dialysis patients. C1 THOMAS JEFFERSON UNIV,DEPT MED,DIV INFECT DIS,PHILADELPHIA,PA 19107. FOX CHASE CANC CTR,DIV POPULAT SCI,PHILADELPHIA,PA. NICHHD,BETHESDA,MD. EHIME UNIV,SCH MED,DEPT INTERNAL MED 3,MATSUYAMA,EHIME 790,JAPAN. RP FEITELSON, MA (reprint author), THOMAS JEFFERSON UNIV,DEPT PATHOL ANAT & CELL BIOL,ROOM 219 ALUMNI HALL,1020 LOCUST ST,PHILADELPHIA,PA 19107, USA. FU NCI NIH HHS [CA-06927, CA-40737]; NCRR NIH HHS [RR-05895] NR 40 TC 30 Z9 31 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1995 VL 172 IS 3 BP 713 EP 722 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RR073 UT WOS:A1995RR07300013 PM 7658063 ER PT J AU POLLACK, M ESPINOZA, AM GUELDE, G KOLES, NL WAHL, LM OHL, CA AF POLLACK, M ESPINOZA, AM GUELDE, G KOLES, NL WAHL, LM OHL, CA TI LIPOPOLYSACCHARIDE (LPS)-SPECIFIC MONOCLONAL-ANTIBODIES REGULATE LPS UPTAKE AND LPS-INDUCED TUMOR-NECROSIS-FACTOR-ALPHA RESPONSES BY HUMAN MONOCYTES SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID BINDING-PROTEIN; BACTERIAL LIPOPOLYSACCHARIDE; FACTOR SECRETION; MACROPHAGES; CELLS; RECEPTOR; CD14; LEUKOCYTES; ENDOTOXIN; COMPLEXES AB Lipopolysaccharide (LPS)-monocyte/macrophage interactions are central to the infected host's inflammatory response to gram-negative bacteria. Flow cytometry was used to analyze the regulation by LPS-specific monoclonal antibodies (MAbs) of fluorescein isothiocyanate-conjugated LPS uptake by human peripheral blood monocytes. The uptake of LPS was stimulated by fresh or heat-inactivated serum (NHS or Delta NHS) or by LPS-binding protein and inhibited by alpha-LPS or alpha-CD14 (LPS receptor) MAbs. The inhibition by alpha-LPS MAbs of CD14-mediated LPS uptake was offset in the presence of NHS by a simultaneous MAb-mediated increase in LPS uptake that was blocked by alpha-complement receptor 1. Monocyte tumor necrosis factor-alpha responses to LPS were augmented by NHS and Delta NHS and inhibited by alpha-LPS MAbs. Thus, alpha-LPS MAbs down-regulate the proinflammatory uptake of LPS by human monocytes,ia membrane-bound CD14 while promoting complement-mediated opsonic uptake through membrane-associated CR1. C1 NIDR,BETHESDA,MD 20892. RP POLLACK, M (reprint author), UNIFORMED SERV UNIV HLTH SCI,F EDWARD HEBERT SCH MED,DEPT MED,4301 JONES BRIDGE RD,BETHESDA,MD 20814, USA. FU NIAID NIH HHS [AI-22706] NR 38 TC 17 Z9 17 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1995 VL 172 IS 3 BP 794 EP 804 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RR073 UT WOS:A1995RR07300024 PM 7658073 ER PT J AU BRADLEY, JE ELSON, L TREE, TIM STEWART, G GUDERIAN, R CALVOPINA, M PAREDES, W ARAUJO, E NUTMAN, TB AF BRADLEY, JE ELSON, L TREE, TIM STEWART, G GUDERIAN, R CALVOPINA, M PAREDES, W ARAUJO, E NUTMAN, TB TI RESISTANCE TO ONCHOCERCA-VOLVULUS - DIFFERENTIAL CELLULAR AND HUMORAL RESPONSES TO A RECOMBINANT ANTIGEN, OVMBP20/11 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID MEDIATED IMMUNE-RESPONSES; IGG SUBCLASS ANTIBODIES; HUMAN FILARIASIS; PUTATIVELY IMMUNE; PARASITE ANTIGEN; INFECTION; SCHISTOSOMIASIS; RESPONSIVENESS; IDENTIFICATION; INTERLEUKIN-4 AB Persons putatively immune (PI) to Onchocerca volvulus (Ov) infection were identified in Ecuador on the basis of epidemiologic, clinical, and parasitologic findings. Immune responses of PI subjects to a recombinant onchocercal protein, OvMBP20/11, were determined and compared with those of a comparable infected (INF) group from the same Ov-endemic area, PI subjects had significantly less antibody reactivity to this molecule; however, not all INF subjects had an antibody response. IgG1 and IgG4 were the predominant IgG subclasses induced to this molecule, and the amount of IgG1 produced was the only significant difference between the PI and IMF groups, In contrast to the antibody responses, proliferative responses to OvMBP20/11 were significantly higher in PI than in INF subjects. Cytokine analysis of peripheral blood mononuclear cell culture supernatants revealed that INF subjects produced significantly more interleukin-10 in response to OvMBP20/11 than did PI subjects. This antigen induced few other cytokines, and there were no differences between study groups. C1 UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,DEPT BIOL,LONDON,ENGLAND. HOSP VOZANDES,INVEST CLIN,QUITO,ECUADOR. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. OI Bradley, Janette/0000-0003-3973-7977 NR 37 TC 29 Z9 29 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 SEP PY 1995 VL 172 IS 3 BP 831 EP 837 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RR073 UT WOS:A1995RR07300029 PM 7658078 ER PT J AU JANOFF, EN WAHL, SM THOMAS, K SMITH, PD AF JANOFF, EN WAHL, SM THOMAS, K SMITH, PD TI MODULATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION OF HUMAN MONOCYTES BY IGA SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID ANTIBODY-DEPENDENT ENHANCEMENT; HIV-INFECTION; FC; MACROPHAGES; VACCINE; CELLS; SERUM AB The effect of IgA from human immunodeficiency virus type 1 (HIV-1)-infected patients on infection of primary human blood monocytes with the monocyte-tropic strain HIV-1(Bal) was evaluated in vitro. Preincubation of HIV-1(Bal) with purified serum IgA from 6 of 14 patients but from none of 5 seronegative subjects caused a >50% increase in reverse transcriptase activity. This increase was inhibited by preincubation of monocytes with nonimmune IgA, suggesting a role for Fccu receptors. Results were independent of CD4 T cell number and clinical stage. The IgA-mediated enhancement extended to more biologically relevant human mononuclear cells isolated from the intestinal lamina propria. The ability of serum IgA to enhance HIV-1 infection may be relevant to infection of both circulating monocytes and mucosal macrophages. These studies suggest the need to characterize the complex contribution of IgA and the mucosal immune system in promoting and preventing primary HIV-1 infection. C1 NIDR,IMMUNOL LAB,BETHESDA,MD 20892. UNIV ALABAMA,DEPT MED,DIV GASTROENTEROL & HEPATOL,BIRMINGHAM,AL. RP JANOFF, EN (reprint author), UNIV MINNESOTA,SCH MED,VET ADM MED CTR,DEPT MED,INFECT DIS SECT 111F,1 VET DR,MINNEAPOLIS,MN 55417, USA. FU NIAID NIH HHS [AI-31373]; NIDCR NIH HHS [DE-42600]; NIDDK NIH HHS [DK-47322] NR 15 TC 19 Z9 21 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 SEP PY 1995 VL 172 IS 3 BP 855 EP 858 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RR073 UT WOS:A1995RR07300033 PM 7658082 ER PT J AU MALONEY, EM PATE, E WIKTOR, SZ MORAIS, P MANN, D GRAY, R MANNS, A BLATTNER, WA AF MALONEY, EM PATE, E WIKTOR, SZ MORAIS, P MANN, D GRAY, R MANNS, A BLATTNER, WA TI THE RELATIVE DISTRIBUTION OF T-CELL SUBSETS IS ALTERED IN JAMAICAN CHILDREN INFECTED WITH HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID HTLV-I; LEUKEMIA LYMPHOMA; TRANSMISSION; DERMATITIS; MOTHER; BABIES AB Early childhood infection with human T cell lymphotropic virus type I (HTLV-T) has been suggested to be involved in the pathogenesis of infective dermatitis and adult T cell leukemia/lymphoma, Since only a very small percentage of HTLV-I-infected children develop disease later in life, identification of early interim markers for persons at risk for developing disease would enable monitoring and might provide insight into the pathophysiology of the various diseases associated with HTLV-I infection, A cross-sectional study analyzed T cell subsets in 35 HTLV-I-seronegative and 16 HTLV-I-seropositive Jamaican children 11-31 months old, HTLV-I seropositivity was associated with an increase in the mean percentage of CD4 cells expressing HLA-DR, a marker for T cell activation (P = .02). This increase was positively correlated with duration of infection (r = .74, P = .009), These data demonstrate perturbation of regulatory cells of the immune system in HTLV-I-infected children. C1 NCI,FREDERICK CANC RES & DEV FACIL,IMMUNOGENET SECT,FREDERICK,MD. UNIV W INDIES,DEPT CHILD HLTH,KINGSTON 7,JAMAICA. RP MALONEY, EM (reprint author), NCI,VIRAL EPIDEMIOL BRANCH,6130 EXECUT BLVD,ROOM 434,ROCKVILLE,MD 20852, USA. NR 13 TC 5 Z9 6 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 SEP PY 1995 VL 172 IS 3 BP 867 EP 870 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RR073 UT WOS:A1995RR07300036 PM 7658085 ER PT J AU CLARK, P EICHHORN, GL AF CLARK, P EICHHORN, GL TI A SIMPLE PROBE FOR DNA ACCESSIBILITY IN CHROMATIN SO JOURNAL OF INORGANIC BIOCHEMISTRY LA English DT Article AB When DNA is treated with Cu(II) and then heated, the melting temperature (T-m) of the DNA is dramatically decreased (8). The Cu(II) binds to the DNA in such a way as to destabilize the double helix and help to break the hydrogen bonds between the bases. When soluble chromatin is similarly treated with Cu(II) and heated, the T-m is unaffected. Apparently the Cu(II) cannot penetrate the chromatin structure and thus cannot initiate the DNA destabilization process. However, when H-1 histone is removed from the chromatin by affinity chromatography, subsequent treatment with Cu(II) does lead to a lowered T-m when the chromatin is heated. This T-m lowering is also achieved by two less drastic techniques that do not remove histone H-1, but decrease the affinity of the H-1 to the DNA: (1) a mild acetylation procedure that specifically modifies either 2 or 4 epsilon-amino groups of lysines on the H-1 histone, and (2) reaction with phosphate-binding divalent metal ions, e.g., Mg(II), Mn(II), or Co(II). Apparently, removal of H-1 or decreased affinity of H-1 for DNA increases the accessibility of the DNA to the Cu(II). This phenomenon suggests a very simple qualitative probe for the degree of structural change in chromatin produced by a change in the stability of the DNA-H-1 interaction. C1 NIA,GERONTOL RES CTR,CELLULAR & MOLEC BIOL LAB,BALTIMORE,MD 21224. NR 25 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0162-0134 J9 J INORG BIOCHEM JI J. Inorg. Biochem. PD SEP PY 1995 VL 59 IS 4 BP 765 EP 772 DI 10.1016/0162-0134(94)00057-H PG 8 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA RP586 UT WOS:A1995RP58600001 PM 7595465 ER PT J AU RICHARD, G KORGE, BP WRIGHT, AR MAZZANTI, C HARTH, W ANNICCHIARICOPETRUZZELLI, M COMPTON, JG BALE, SJ AF RICHARD, G KORGE, BP WRIGHT, AR MAZZANTI, C HARTH, W ANNICCHIARICOPETRUZZELLI, M COMPTON, JG BALE, SJ TI HAILEY-HAILEY DISEASE MAPS TO A 5 CM INTERVAL ON CHROMOSOME 3Q21-Q24 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE GENODERMATOSIS; EPIDERMIS; LINKAGE; FAMILIAL BENIGN CHRONIC PEMPHIGUS ID BENIGN CHRONIC PEMPHIGUS AB Hailey-Hailey disease (HHD) is a rare autosomal dominant genodermatosis characterized by disturbed keratinocyte adhesion. The disease has recently been mapped to a 14cM region on chromosome 3q. We have further refined the location of the HHD gene by linkage analysis in six HHD families from Germany and Italy using 11 polymorphic microsatellite markers and found no evidence for genetic heterogeneity. We observed complete cosegregation between HHD and marker D3S1587, with a maximal lod score of 4.54. Detailed haplotype analyses allowed us to narrow the interval containing the HHD locus to 5cM, flanked by D3S1589 and D3S1290. C1 NIAMS,SKIN BIOL LAB,BETHESDA,MD 20892. UNIV COLOGNE,DERMATOL KLIN & POLIKLIN,COLOGNE,GERMANY. IST DERMOPAT IMMACOLATA,ROME,ITALY. HAUTKLIN ERFURT,ERFURT,GERMANY. UNIV ROMA TOR VERGATA,DEPT EXPTL MED,BIOCHEM IDI,IRCCS LAB,ROME,ITALY. NR 29 TC 17 Z9 20 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1995 VL 105 IS 3 BP 357 EP 360 DI 10.1111/1523-1747.ep12320741 PG 4 WC Dermatology SC Dermatology GA RU399 UT WOS:A1995RU39900009 PM 7665912 ER PT J AU HENGGE, UR WALKER, PS FOSTER, RA VOGEL, JC AF HENGGE, UR WALKER, PS FOSTER, RA VOGEL, JC TI EPIDERMIS AS TARGET FOR IN-VIVO GENE-THERAPY SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,DERMATOL BRANCH,BETHESDA,MD. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1995 VL 105 IS 3 BP 448 EP 448 PG 1 WC Dermatology SC Dermatology GA RU399 UT WOS:A1995RU39900029 ER PT J AU WIENECKE, R KONIG, A LOWRY, DR DECLUE, JE AF WIENECKE, R KONIG, A LOWRY, DR DECLUE, JE TI IDENTIFICATION OF THE 180-KDA PROTEIN PRODUCT (TUBERIN) OF THE TUBEROUS SCLEROSIS-2 GENE AND CHARACTERIZATION AS A PROTEIN WITH SPECIFIC RAP1GAP ACTIVITY SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1995 VL 105 IS 3 BP 448 EP 448 PG 1 WC Dermatology SC Dermatology GA RU399 UT WOS:A1995RU39900028 ER PT J AU CAVANI, A KATZ, SI AF CAVANI, A KATZ, SI TI CONTACT SENSITIVITY IN MHC CLASS-II DEFICIENT MICE IS ENHANCED SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1995 VL 105 IS 3 BP 450 EP 450 PG 1 WC Dermatology SC Dermatology GA RU399 UT WOS:A1995RU39900039 ER PT J AU FIEBIGER, E MAURER, D HOLUB, H REININGER, B HARTMANN, G WOISETSCHLAGER, M KINET, JP STINGL, G AF FIEBIGER, E MAURER, D HOLUB, H REININGER, B HARTMANN, G WOISETSCHLAGER, M KINET, JP STINGL, G TI SERUM IGG AUTOANTIBODIES DIRECTED AGAINST THE ALPHA-CHAIN OF FC-EPSILON-RI - A SELECTIVE MARKER FOR A DISTINCT SUBSET OF CHRONIC URTICARIA PATIENTS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV VIENNA,SCH MED,DEPT DERMATOL,VIENNA,AUSTRIA. SANDOZ PHARMA AG,RES INST,VIENNA,AUSTRIA. NIAID,MOLEC ALLERGY & IMMUNOL SECT,ROCKVILLE,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1995 VL 105 IS 3 BP 453 EP 453 PG 1 WC Dermatology SC Dermatology GA RU399 UT WOS:A1995RU39900056 ER PT J AU HERTL, M AMAGAI, M SUNDARAM, H STANLEY, J ISHII, K KATZ, SI AF HERTL, M AMAGAI, M SUNDARAM, H STANLEY, J ISHII, K KATZ, SI TI CHARACTERIZATION OF T-CELL EPITOPES OF THE PEMPHIGUS-VULGARIS ANTIGEN (PVA) SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,DERMATOL BRANCH,BETHESDA,MD. KEIO UNIV,TOKYO,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1995 VL 105 IS 3 BP 454 EP 454 PG 1 WC Dermatology SC Dermatology GA RU399 UT WOS:A1995RU39900061 ER PT J AU COURTOIS, SJ DEGREEF, H WOODWORTH, CD GARMYN, M AF COURTOIS, SJ DEGREEF, H WOODWORTH, CD GARMYN, M TI EFFECTS OF RESTORATION OF WILD-TYPE P53 EXPRESSION IN MALIGNANT KERATINOCYTES SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 KATHOLIEKE UNIV LEUVEN,DERMATOL LAB,B-3000 LOUVAIN,BELGIUM. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1995 VL 105 IS 3 BP 459 EP 459 PG 1 WC Dermatology SC Dermatology GA RU399 UT WOS:A1995RU39900096 ER PT J AU RICHARD, G KORGE, BP WRIGHT, AR MAZZANTI, C COMPTON, JG BALE, SJ AF RICHARD, G KORGE, BP WRIGHT, AR MAZZANTI, C COMPTON, JG BALE, SJ TI FINE MAPPING OF THE GENE OF HAILEY-HAILEY DISEASE TO A 5CM INTERVAL ON CHROMOSOME 3Q SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS,SKIN BIOL LAB,BETHESDA,MD 20892. UNIV COLOGNE,DERMATOL KLIN & POLIKLIN,COLOGNE,GERMANY. IST DERMOPAT IMMACOLATA,ROME,ITALY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1995 VL 105 IS 3 BP 459 EP 459 PG 1 WC Dermatology SC Dermatology GA RU399 UT WOS:A1995RU39900094 ER PT J AU MAURER, D EBNER, H REININGER, B FIEBIGER, E KRAFT, D KINET, JP STINGL, G AF MAURER, D EBNER, H REININGER, B FIEBIGER, E KRAFT, D KINET, JP STINGL, G TI PERIPHERAL-BLOOD DENDRITIC CELLS EXPRESS FUNCTIONAL FC-EPSILON-RI SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV VIENNA,SCH MED,DEPT DERMATOL & GEN & EXP PATHOL,VIENNA,AUSTRIA. NIAID,MOLEC ALLERGY & IMMUNOL SECT,ROCKVILLE,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1995 VL 105 IS 3 BP 474 EP 474 PG 1 WC Dermatology SC Dermatology GA RU399 UT WOS:A1995RU39900181 ER PT J AU FARTASCH, M SINDRANSKY, E ELIAS, PM GINNS, EI HOLLERAN, WM AF FARTASCH, M SINDRANSKY, E ELIAS, PM GINNS, EI HOLLERAN, WM TI UNIQUE EPIDERMAL ABNORMALITIES DUE TO SEVERE GLUCOCEREBROSIDASE DEFICIENCY IN TYPE-II GAUCHER DISEASE SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV ERLANGEN NURNBERG,DEPT DERMATOL,W-8520 ERLANGEN,GERMANY. NIMH,CLIN NEUROSCI BRANCH,MOLEC NEUROGENET SECT,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,VET ADM MED CTR,DERMATOL SERV,SAN FRANCISCO,CA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1995 VL 105 IS 3 BP 479 EP 479 PG 1 WC Dermatology SC Dermatology GA RU399 UT WOS:A1995RU39900215 ER PT J AU CHARVAT, B SHAH, K MOUNTS, P KASHIME, H LOWY, D SCHILLER, J KIRNBAUER, R AF CHARVAT, B SHAH, K MOUNTS, P KASHIME, H LOWY, D SCHILLER, J KIRNBAUER, R TI TYPE-SPECIFICITY OF THE IMMUNE-RESPONSE TO PAPILLOMAVIRUS-LIKE PARTICLES IN PATIENTS WITH RECURRENT RESPIRATORY SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV VIENNA,DEPT DERMATOL,DIV IMMUNODERMATOL DIAID,VIENNA,AUSTRIA. JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1995 VL 105 IS 3 BP 496 EP 496 PG 1 WC Dermatology SC Dermatology GA RU399 UT WOS:A1995RU39900315 ER PT J AU KLUBAL, R MAURER, D OSTERHOFF, B KINET, JP STINGL, G AF KLUBAL, R MAURER, D OSTERHOFF, B KINET, JP STINGL, G TI THE ACCUMULATION OF FC-EPSILON-RI+ RFD1+ DERMAL DENDRITIC CELLS IS NOT RESTRICTED TO ATOPIC-DERMATITIS SKIN SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV VIENNA,SCH MED,DEPT DERMATOL,DIAID,VIENNA,AUSTRIA. UNIV VIENNA,SCH MED,VIRCC,VIENNA,AUSTRIA. NIAID,MOLEC ALLERGY & IMMUNOL SECT,ROCKVILLE,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1995 VL 105 IS 3 BP 501 EP 501 PG 1 WC Dermatology SC Dermatology GA RU399 UT WOS:A1995RU39900344 ER PT J AU YANG, SK BAO, ZP SHOU, MG AF YANG, SK BAO, ZP SHOU, MG TI A ONE-STEP SYNTHESIS OF [3-H-2]OXAZEPAM SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE OXAZEPAM; KETO-ENOL TAUTOMERISM; DEUTERIUM EXCHANGE; MASS SPECTROMETRY ID 1,4-BENZODIAZEPINES; CHROMATOGRAPHY AB The proton at 3-position of oxazepam (7-chloro-1,3-dihydro-3-hydroxy-5-phenyl-2H-1, 4-benzodiazepin-2-one) undergoes a deuterium exchange in deuterated alkaline methanol. A base-catalyzed keto-enol tautomerism is proposed to be responsible for the observed deuterium exchange. This simple method is a considerable improvement of the multi-step synthetic procedure reported in the literature. C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RP YANG, SK (reprint author), UNIFORMED SERV UNIV HLTH SCI,F EDWARD HEBERT SCH MED,DEPT PHARMACOL,BETHESDA,MD 20814, USA. NR 10 TC 4 Z9 4 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD SEP PY 1995 VL 36 IS 9 BP 861 EP 869 DI 10.1002/jlcr.2580360907 PG 9 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA RQ810 UT WOS:A1995RQ81000006 ER PT J AU HUMMERT, ML GARSTKA, TA SHANER, JL AF HUMMERT, ML GARSTKA, TA SHANER, JL TI BELIEFS ABOUT LANGUAGE PERFORMANCE - ADULTS PERCEPTIONS ABOUT SELF AND ELDERLY TARGETS SO JOURNAL OF LANGUAGE AND SOCIAL PSYCHOLOGY LA English DT Article; Proceedings Paper CT Speech-Communication-Association Convention CY NOV, 1994 CL NEW ORLEANS, LA SP Speech Commun Assoc ID BABY TALK; AGE; COMMUNICATION; STEREOTYPES AB Stereotypes of the elderly may lead to beliefs about their communication competence. To test this hypothesis, the Language in Adulthood Quuestionnaire (LIA) (Ryan, Kwong See, Meneer; and Trovato, 1992) was used to assess beliefs of young, middle-aged, and elderly adults about their own language stills and those of four elderly targets. Targets represented two positive (Golden Ager, John Wayne Conservative) and two negative (Despondent,, Shrew/Curmudgeon) stereotypes of older adults. As expected, elderly respondents reported more language problems than, did the middle-aged and young. However, contrary to expectations, middle-aged respondents reported no more problems than the young, and elderly respondents showed no advantage in skills shown to improve with age. Assessments of the targets supported the hypothesis that beliefs about language skills vary with the characteristics of older individuals and do not derive solely from their categorization as elderly. C1 UNIV KANSAS,CTR GERONTOL,LAWRENCE,KS 66045. NIA,BALTIMORE,MD 21224. UNIV KANSAS,DEPT PSYCHOL,LAWRENCE,KS 66045. RP HUMMERT, ML (reprint author), UNIV KANSAS,DEPT COMMUN STUDIES,LAWRENCE,KS 66045, USA. NR 37 TC 16 Z9 16 U1 1 U2 4 PU SAGE PUBL INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0261-927X J9 J LANG SOC PSYCHOL JI J. Lang. Soc. Psychol. PD SEP PY 1995 VL 14 IS 3 BP 235 EP 259 DI 10.1177/0261927X95143001 PG 25 WC Communication; Linguistics; Psychology, Social SC Communication; Linguistics; Psychology GA RP270 UT WOS:A1995RP27000001 ER PT J AU DEHOOG, GS GUEHO, E MASCLAUX, F VANDENENDE, AHG KWONCHUNG, KJ MCGINNIS, MR AF DEHOOG, GS GUEHO, E MASCLAUX, F VANDENENDE, AHG KWONCHUNG, KJ MCGINNIS, MR TI NUTRITIONAL PHYSIOLOGY AND TAXONOMY OF HUMAN-PATHOGENIC CLADOSPORIUM-XYLOHYPHA SPECIES SO JOURNAL OF MEDICAL AND VETERINARY MYCOLOGY LA English DT Article ID SP-NOV; TRICHOIDES; PHAEOHYPHOMYCOSIS; BANTIANA; DERMATITIDIS; ANAMORPHS; DEVRIESII; EMMONSII; FUNGI AB Physiological profiles of type, authentic and some additional isolates of Cladosporium-Xylohypha species of purported herpotrichiellaceous relationship are established. This group comprises melanized catenate hyphomycetes which are prevalently found on the human host. The species are excluded from the genus Cladosporium and are classified in the genus Cladophialophora. Taeniolella boppii is also transferred to this genus. Cladosporium bantianum (= Xylohypha emmonsii) and C. trichoides are considered conspecific and are now referred to as Cladophialophora bantiana. Meso-erythritol, L-arabinitol, ethanol and growth at 40 degrees C are found to be the most useful criteria for species distinction. The species Cladosporium carrionii is found to be heterogeneous. The anamorph of the saprophytic ascomycete Capronia pilosella is morphologically similar to an authentic strain of Cladosporium carrionii, but physiologically distinct. A diagnostic key for the recognized Cladophialophora species and to morphologically similar taxa is provided. C1 BIOCENTRUM AMSTERDAM,INST MOLEC CELL BIOL,1098 SM AMSTERDAM,NETHERLANDS. INST PASTEUR,UNITE MYCOL,F-75724 PARIS 15,FRANCE. NIH,BETHESDA,MD 20892. UNIV TEXAS,MED BRANCH,CTR TROP DIS,MED MYCOL RES CTR,GALVESTON,TX 77555. RP DEHOOG, GS (reprint author), CENT BUR SCHIMMELCULTURES,POB 273,3740 AG BAARN,NETHERLANDS. NR 44 TC 60 Z9 62 U1 1 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0268-1218 J9 J MED VET MYCOL JI J. Med. Vet. Mycol. PD SEP-OCT PY 1995 VL 33 IS 5 BP 339 EP 347 PG 9 WC Mycology SC Mycology GA RZ077 UT WOS:A1995RZ07700009 PM 8544087 ER PT J AU KOTIAN, P ABRAHAM, P LEWIN, AH MASCARELLA, SW BOJA, JW KUHAR, MJ CARROLL, FI AF KOTIAN, P ABRAHAM, P LEWIN, AH MASCARELLA, SW BOJA, JW KUHAR, MJ CARROLL, FI TI SYNTHESIS AND LIGAND-BINDING STUDY OF 3-BETA-(4'-SUBSTITUTED PHENYL)-2-BETA-(HETEROCYCLIC)TROPANES SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Note ID COCAINE RECEPTOR; WAVE-FUNCTIONS; DERIVATIVES; ANALOGS C1 RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NIDA,ADDICT RES CTR,NEUROSCI BRANCH,BALTIMORE,MD 21224. OI Mascarella, Wayne/0000-0003-0092-8178 FU NIDA NIH HHS [DA05477] NR 22 TC 23 Z9 23 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD SEP 1 PY 1995 VL 38 IS 18 BP 3451 EP 3453 DI 10.1021/jm00018a004 PG 3 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA RR904 UT WOS:A1995RR90400004 PM 7658431 ER PT J AU CHATTON, JY SPRING, KR AF CHATTON, JY SPRING, KR TI THE SODIUM CONCENTRATION OF LATERAL INTERCELLULAR SPACES - REPLY SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Letter C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. RP CHATTON, JY (reprint author), UNIV BERN,INST PHARMACOL,BERN,SWITZERLAND. NR 4 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD SEP PY 1995 VL 147 IS 1 BP 106 EP 107 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA RU635 UT WOS:A1995RU63500010 ER PT J AU ARISPE, N DEMAZANCOURT, P ROJAS, E AF ARISPE, N DEMAZANCOURT, P ROJAS, E TI DIRECT CONTROL OF A LARGE-CONDUCTANCE K+-SELECTIVE CHANNEL BY G-PROTEINS IN ADRENAL CHROMAFFIN GRANULE MEMBRANES SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE K+-CHANNEL; G-PROTEIN; SECRETORY VESICLES; ANTIBODIES; GTP-GAMMA-S; GDP-BETA-S ID REGULATORY PROTEINS; BINDING PROTEINS; GOLGI MEMBRANES; ALPHA; CELLS; ACTIVATION; RECEPTOR; SUBUNIT; EXOCYTOSIS; ANTIBODIES AB We report here the presence of a Ca2+-independent K+-channel of large conductance in adrenal chromaffin cell secretory vesicle membranes which is controlled by inhibitory as well as stimulatory heterotrimeric GTP-binding proteins. Using antibodies against specific alpha subunits for immunoblot analysis, we were able to identify the presence of the inhibitory G(i2) and G(i3) subtypes, as well as the stimulatory G(o) and G(s) subtypes, but not G(i1) in adrenal chromaffin granules. Furthermore, functional analysis of the Kf-channel incorporated into planar lipid bilayers showed that GDP beta S and GTP gamma S have opposite effects on channel activity inducing interconversions between a low and a high open-probability state. Consistent with these findings, the same antibodies antagonized the effects of the nonhydrolyzable analogues on the open probability of the K+-channel. RP ARISPE, N (reprint author), NIDDK,CELL BIOL & GENET LAB,MOLEC PATHOPHYSIOL BRANCH,BETHESDA,MD 20892, USA. NR 37 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD SEP PY 1995 VL 147 IS 2 BP 109 EP 119 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA RW498 UT WOS:A1995RW49800001 PM 8568848 ER PT J AU BAKER, JT BORRIS, RP CARTE, B CORDELL, GA SOEJARTO, DD CRAGG, GM GUPTA, MP IWU, MM MADULID, DR TYLER, VE AF BAKER, JT BORRIS, RP CARTE, B CORDELL, GA SOEJARTO, DD CRAGG, GM GUPTA, MP IWU, MM MADULID, DR TYLER, VE TI NATURAL PRODUCT DRUG DISCOVERY AND DEVELOPMENT - NEW PERSPECTIVES ON INTERNATIONAL COLLABORATION SO JOURNAL OF NATURAL PRODUCTS-LLOYDIA LA English DT Article ID MEDICINAL-PLANTS; IN-VIVO AB Until recently, the prevailing attitude in developed nations regarded the world's genetic resources, which are mainly concentrated in the developing world, as a common resource of humankind, to be exploited freely irrespective of national origin. With the devastation being wreaked in the tropical rainforests and the resurgence in interest in recent years in the discovery of novel drugs from natural sources, particularly plants and marine organisms, the international scientific community has realized that the conservation of these global genetic resources and the indigenous knowledge associated with their use are of primary importance if their potential is to be fully explored. With this realization has come a recognition that these goals must be achieved through collaboration with, and fair and equitable compensation of, the scientists and communities of the genetically rich source countries. The signing of the United Nations Convention on Biological Diversity by nearly all of the world's nations has emphasized the need for the implementation of such policies. In this review, the articles of the Convention of relevance to the activities and practices of the natural products scientific community are briefly discussed. This discussion is followed by a summary of policies for international collaboration and compensation being implemented by several developed country organizations, and the perspectives on the current developments given by representatives of some of the source countries located in the regions of greatest biodiversity. C1 AUSTRALIAN INST MARINE SCI,TOWNSVILLE,QLD 4810,AUSTRALIA. MERCK RES LABS,RAHWAY,NJ 07065. SMITHKLINE BEECHAM PHARMACEUT,KING OF PRUSSIA,PA 19406. UNIV ILLINOIS,COLL PHARM,DEPT MED CHEM & PHARMACOGNOSY,PROGRAM COLLABORAT RES PHARMACEUT SCI,CHICAGO,IL 60612. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,NAT PROD BRANCH,FREDERICK,MD 21702. UNIV PANAMA,COLL PHARM,CTR PHARMACOGNOST RES PANAMANIAN FLORA,PANAMA CITY,PANAMA. WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,WASHINGTON,DC 20307. NATL MUSEUM,DIV BOT,MANILA,PHILIPPINES. PURDUE UNIV,SCH PHARM & PHARMACEUT SCI,DEPT MED CHEM & PHARMACOGNOSY,W LAFAYETTE,IN 47907. RI Borris, Robert/K-1095-2015; OI Borris, Robert/0000-0002-5317-7382; Gupta, Mahabir/0000-0002-9302-7864 NR 44 TC 128 Z9 136 U1 1 U2 13 PU AMER SOC PHARMACOGNOSY PI CINCINNATI PA LLOYD LIBRARY & MUSEUM 917 PLUM ST, CINCINNATI, OH 45202 SN 0163-3864 J9 J NAT PRODUCTS JI J. Nat. Prod. PD SEP PY 1995 VL 58 IS 9 BP 1325 EP 1357 DI 10.1021/np50123a003 PG 33 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA TB928 UT WOS:A1995TB92800003 PM 7494142 ER PT J AU PARLOFF, MB AF PARLOFF, MB TI HOUSE OF CARDS - PSYCHOLOGY AND PSYCHOTHERAPY BUILT ON MYTH - DAWES,RM SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review C1 NIMH,PSYCHOSOCIAL TREATMENTS RES BRANCH,BETHESDA,MD 20892. RP PARLOFF, MB (reprint author), GEORGETOWN UNIV,SCH MED,WASHINGTON,DC 20057, USA. NR 2 TC 0 Z9 0 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD SEP PY 1995 VL 183 IS 9 BP 608 EP 609 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA RX660 UT WOS:A1995RX66000011 ER PT J AU DAMSCHRODERWILLIAMS, P IRWIN, RP LIN, SZ PAUL, SM AF DAMSCHRODERWILLIAMS, P IRWIN, RP LIN, SZ PAUL, SM TI CHARACTERIZATION OF THE EXCITOPROTECTIVE ACTIONS OF N-METHYL-D-ASPARTATE IN CULTURED CEREBELLAR GRANULE NEURONS SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE CEREBELLAR GRANULE NEURONS; NMDA RECEPTOR; EXCITOPROTECTION; PROTEIN SYNTHESIS; NEURONAL DEVELOPMENT ID RECEPTOR AGONISTS; CELLS; GLUTAMATE; TOXICITY; 1-METHYL-4-PHENYLPYRIDINIUM; DIFFERENTIATION; NEUROTOXICITY; SURVIVAL; NMDA; RNA AB Exposure of cultured cerebellar granule neurons to subtoxic concentrations of N-methyl-D-aspartate (NMDA) has been shown previously to result in a neuroprotective state, as measured by subsequent exposure to toxic concentrations of glutamate. In the present study, we have further characterized the excitoprotective actions of NMDA in these neurons. NMDA-induced excitoprotection was concentration dependent (EC(50) similar to 30 mu M) and time dependent, with maximal protection observed following 16 h of preexposure to NMDA. NMDA-induced excitoprotection did not require continuous exposure to NMDA, as a 4-h preincubation was sufficient to induce full excitoprotection when measured 8 h later. Maximal protection was manifest as a ''right shift'' in the concentration-response relationship for glutamate toxicity of approximately three orders of magnitude (EC(50) similar to 30 mu M in untreated neurons compared with greater than or equal to 50 mM in NMDA-treated neurons). After removal of NMDA, complete reversal of the excitoprotective state was observed by 48 h (t(1/2) approximate to 24 h). The ability of NMDA to induce excitoprotection was observed in neurons maintained for up to 14 days in vitro (DIV) [postnatal day (PND) 22], but was absent at 21 and 32 DIV (PND 29-40), despite little to no difference in the toxicity of glutamate at any DIV examined. Preexposure of cerebellar granule neurons to a maximally excitoprotective concentration of NMDA (50 mu M) failed to alter the density of NMDA receptors measured by the specific binding of [H-3]MK-801. Moreover, the immediate elevation in intracellular free calcium concentration ([Ca2+](i)) induced by glutamate exposure and measured by microfluorimetry and the Ca2+-sensitive indicator fura-2 was similar in NMDA-pretreated and untreated neurons. As reported previously, NMDA-induced excitoprotection in cerebellar granule neurons was, however, reversed by coincubation with the protein synthesis inhibitor cycloheximide. Taken together, these data suggest that NMDA receptor-mediated excitoprotection in cerebellar granule neurons is mediated via both a transcriptionally directed and a developmentally regulated postreceptor mechanism(s). C1 ELI LILLY & CO, LILLY CORP CTR, LILLY RES LABS, INDIANAPOLIS, IN 46285 USA. INDIANA UNIV, SCH MED, DEPT PHARMACOL & TOXICOL, INDIANAPOLIS, IN 46202 USA. INDIANA UNIV, SCH MED, DEPT MED, INDIANAPOLIS, IN 46202 USA. INDIANA UNIV, SCH MED, DEPT PSYCHIAT, INDIANAPOLIS, IN 46202 USA. NIMH, CLIN NEUROSCI BRANCH, MOLEC PHARMACOL SECT, BETHESDA, MD 20892 USA. NR 27 TC 30 Z9 30 U1 0 U2 1 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 1995 VL 65 IS 3 BP 1069 EP 1076 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA RQ571 UT WOS:A1995RQ57100014 PM 7643085 ER PT J AU ZATZ, M HEATH, JR AF ZATZ, M HEATH, JR TI CALCIUM AND PHOTOENTRAINMENT IN CHICK PINEAL CELLS REVISITED - EFFECTS OF CAFFEINE, THAPSIGARGIN, EGTA, AND LIGHT ON THE MELATONIN RHYTHM SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE CIRCADIAN RHYTHMS; CALCIUM; PINEAL CELLS ID INTRACELLULAR CA-2+ STORES; PHOTOENDOCRINE TRANSDUCTION; CIRCADIAN-RHYTHM; OSCILLATIONS; NEURONS; INFLUX; GLAND; PHASE; MECHANISM; SEROTONIN AB Chick pineal cells in dispersed cell culture display a persistent, photosensitive, circadian rhythm of melatonin production and release. Light pulses have at least two distinguishable effects on these cells, i.e., acute suppression of melatonin output and phase shifts (entrainment) of the underlying circadian pacemaker. Previous results linked calcium influx through voltage-sensitive calcium channels in the plasma membrane to acute regulation of melatonin synthesis but denied a role for such influx in entrainment. Those experiments did not, however, address the role of intracellular calcium metabolism. Here we describe the effects of pulses of caffeine, thapsigargin, and EGTA on the melatonin rhythm, and their interactions with the effects of light pulses. Caffeine had two distinguishable effects on these cells, acute enhancement of melatonin output (attributable to phosphodiesterase inhibition) and phase shifts of the circadian pacemaker with a light-like pattern (attributable to effects on intracellular calcium), Phase shifts induced by light and caffeine were not additive, Thapsigargin (which specifically blocks the pump that replenishes intracellular calcium stores, thereby increasing cytoplasmic calcium and depleting intracellular stores) had no phase-shifting effects by itself but reduced the size of the phase advances induced by caffeine or light. Low calcium solution acutely suppressed melatonin output without inducing phase shifts or affecting those induced by caffeine or light. However, addition of EGTA (which specifically chelates calcium, thereby lowering cytoplasmic calcium and depleting intracellular stores) did reduce the size of phase advances induced by caffeine or light, in normal medium or in low calcium solution, without inducing a phase shift by itself at that phase. Taken together, these results point toward a role for intracellular calcium fluxes in entrainment of the circadian pacemaker. RP ZATZ, M (reprint author), NIMH,CELL BIOL LAB,BIOCHEM PHARMACOL SECT,BLDG 36,RM 2A-17,36 CONVENT DR,MSC 4068,BETHESDA,MD 20892, USA. NR 36 TC 27 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 SEP PY 1995 VL 65 IS 3 BP 1332 EP 1341 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA RQ571 UT WOS:A1995RQ57100046 PM 7643111 ER PT J AU PREMKUMAR, DRD SMITH, MA RICHEY, PL PETERSEN, RB CASTELLANI, R KUTTY, RK WIGGERT, B PERRY, G KALARIA, RN AF PREMKUMAR, DRD SMITH, MA RICHEY, PL PETERSEN, RB CASTELLANI, R KUTTY, RK WIGGERT, B PERRY, G KALARIA, RN TI INDUCTION OF HEME OXYGENASE-1 MESSENGER-RNA AND PROTEIN IN NEOCORTEX AND CEREBRAL VESSELS IN ALZHEIMERS-DISEASE SO JOURNAL OF NEUROCHEMISTRY LA English DT Note DE ALZHEIMERS DISEASE; AMYLOID BETA-PROTEIN; ANTIOXIDANTS; CEREBRAL VESSELS; HEAT-SHOCK PROTEINS; HEME OXYGENASE-1; HEME OXYGENASE-2; STRESS PROTEINS ID MESSENGER-RNA; CARBON-MONOXIDE; EXPRESSION; BRAIN; CELLS; RAT; ANTIOXIDANT; STRESS; CDNA AB Previous studies demonstrated the specific association of heme oxygenase (HO)-1 protein to the neurofibrillary pathology of Alzheimer's disease (AD). In this study, we used reverse transcription-polymerase chain reaction methods to show the increased expression of HO-1 but not HO-2 mRNA transcripts in cerebral cortex and cerebral vessels from subjects with AD compared with age-matched non-AD controls. Neither the HO-1 nor the HO-2 mRNA level was altered in the cerebellum, a brain region usually spared from the pathological alterations of AD. There was no clear evidence that the expression of HO-1 in these tissues was related to postmortem interval, cause of death, or the age of the subjects studied. Using immunoblotting methods, we further showed that HO-1 protein content was increased in neocortical and vascular samples from AD subjects compared with controls. Our findings suggest the specific induction of HO-1 mRNA and protein in the cerebral cortex and cerebral vessels but not HO-2 mRNA or protein in association with the pathological lesions of the disease. C1 CASE WESTERN RESERVE UNIV,DEPT NEUROL BRB5,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,DEPT PATHOL,CLEVELAND,OH 44106. NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. RI Smith, Mark/A-9053-2009; Castellani, Rudy/A-9555-2009; Perry, George/A-8611-2009; Petersen, Robert/B-5075-2011 OI Perry, George/0000-0002-6547-0172; Petersen, Robert/0000-0002-3154-0072 FU NIA NIH HHS [AG01003, AG07552, AG08012] NR 26 TC 155 Z9 161 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 1995 VL 65 IS 3 BP 1399 EP 1402 PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA RQ571 UT WOS:A1995RQ57100055 PM 7543935 ER PT J AU PASCUALLEONE, A DANG, N COHEN, LG BRASILNETO, JP CAMMAROTA, A HALLETT, M AF PASCUALLEONE, A DANG, N COHEN, LG BRASILNETO, JP CAMMAROTA, A HALLETT, M TI MODULATION OF MUSCLE RESPONSES EVOKED BY TRANSCRANIAL MAGNETIC STIMULATION DURING THE ACQUISITION OF NEW FINE MOTOR-SKILLS SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID CEREBRAL BLOOD-FLOW; FREQUENCY-DISCRIMINATION TASK; VOLUNTARY MOVEMENTS; BRAILLE READERS; MENTAL PRACTICE; CORTICAL AREAS; CORTEX; REORGANIZATION; REPRESENTATION; PERFORMANCE AB 1. We used transcranial magnetic stimulation (TMS) to study the role of plastic changes of the human motor system in the acquisition of new fine motor skills. We mapped the cortical motor areas targeting the contralateral long finger flexor and extensor muscles in subjects learning a one-handed, five-finger exercise on the piano. In a second experiment, we studied the different effects of mental and physical practice of the same five-finger exercise on the modulation of the cortical motor areas targeting muscles involved in the task. 2. Over the course of 5 days, as subjects learned the one-handed, five-finger exercise through daily 2-h manual practice sessions, the cortical motor areas targeting the long finger flexor and extensor muscles enlarged, and their activation threshold decreased. Such changes were limited to the cortical representation of the hand used in the exercise. No changes of cortical motor outputs occurred in control subjects who underwent daily TMS mapping but did not practice on the piano at all (control group 1). 3. We studied the effect of increased hand use without specific skill learning in subjects who played the piano at will for 2 h each day using only the right hand but who were not taught the five-finger exercise (control group 2) and who did not practice any specific task. In these control subjects, the changes in cortical motor outputs were similar but significantly less prominent than in those occurring in the test subjects, who learned the new skill. 4. In the second experiment, subjects were randomly assigned to a physical practice group, a mental practice group, or a control group. Subjects in each practice group physically or mentally practiced the five-finger piano exercise independently for 2 h daily for 5 days. The control group did not practice the exercise. All subjects had daily TMS mapping of the cortical motor areas targeting the long finger flexor and extensor muscles. 5. Over the course of 5 days, mental practice alone led to significant improvement in the performance of the five-finger exercise, but the improvement was significantly less than that produced by physical practice alone. However, mental practice alone led to the same plastic changes in the motor system as those occurring with the acquisition of the skill by repeated physical practice. 6. We conclude that acquisition of the motor skills needed for the correct performance of a five-finger piano exercise is associated with modulation of the cortical motor outputs to the muscles involved in the task. This rapid modulation may occur through an increase of synaptic efficacy in existing neural circuits (long-term potentiation) or unmasking of existing connections due to disinhibition. 7. Mental practice alone seems to be sufficient to promote the modulation of neural circuits involved in the early stages of motor skill learning. This modulation not only results in marked performance improvement but also seems to place the subjects at an advantage for further skill learning with minimal physical practice. C1 NINCDS, MED NEUROL BRANCH, HUMAN MOTOR CONTROL SECT, HUMAN CONTROL PHYSIOL UNIT, BETHESDA, MD 20892 USA. RI Brasil-Neto, Joaquim/A-1171-2009 NR 58 TC 699 Z9 708 U1 6 U2 57 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 1995 VL 74 IS 3 BP 1037 EP 1045 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA RU952 UT WOS:A1995RU95200012 PM 7500130 ER PT J AU BROWN, VJ DESIMONE, R MISHKIN, M AF BROWN, VJ DESIMONE, R MISHKIN, M TI RESPONSES OF CELLS IN THE TAIL OF THE CAUDATE-NUCLEUS DURING VISUAL-DISCRIMINATION LEARNING SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID INFERIOR TEMPORAL CORTEX; MOVEMENT-RELATED ACTIVITY; BASAL GANGLIA; PARAHIPPOCAMPAL GYRUS; CORTICAL CONNECTIONS; BEHAVIORAL REACTIONS; RECOGNITION MEMORY; DOPAMINE NEURONS; RHESUS-MONKEY; TERM-MEMORY AB 1. The tail of the caudate nucleus and adjacent ventral putamen (ventrocaudal neostriatum) are major projection sites of the extra-striate visual cortex. Visual information is then relayed, directly or indirectly, to a variety of structures with motor functions. To test for a role of the ventrocaudal neostriatum in stimulus-response association learning, or habit formation, neuronal responses were recorded while monkeys performed a visual discrimination task. Additional data were collected from cells in cortical area TF, which serve as a comparison and control for the caudate data. 2. Two monkeys were trained to perform an asymmetrically reinforced go-no go visual discrimination. The stimuli were complex colored patterns, randomly assigned to be either positive or negative. The monkey was rewarded with juice for releasing a bar when a positive stimulus was presented, whereas a negative stimulus signaled that no reward was available and that the monkey should withhold its response. Neuronal responses were recorded both while the monkey performed the task with previously learned stimuli and while it learned the task with new stimuli. In some cases, responses were recorded during reversal learning. 3. There was no evidence that cells in the ventrocaudal neostriatum were influenced by the reward contingencies of the task. Cells did not fire preferentially to the onset of either positive or negative stimuli; neither did cells fire in response to the reward itself or in association with the motor response of the monkey. Only visual responses were apparent. 4. The visual properties of cells in these structures resembled those of cells in some of the cortical areas projecting to them. Most cells responded selectively to different visual stimuli. The degree of stimulus selectivity was assessed with discriminant analysis and was found to be quantitatively similar to that of inferior temporal cells tested with similar stimuli. Likewise, like inferior temporal cells, many cells in the ventrocaudal neostriatum had large, bilateral receptive fields. Some cells had ''doughnut''-shaped receptive fields, with stronger responses in the periphery of both visual fields than at the fovea, similar to the fields of some cells in the superior temporal polysensory area. Although the absence of task-specific responses argues that ventrocaudal neostriatal cells are not themselves the mediators of visual learning in the task employed, their cortical-like visual properties suggest that they might relay visual information important for visuomotor plasticity in other structures. 5. Although there was no evidence of neuronal responses related specifically to the learning of stimulus-response associations in the task, there was a tendency for novel stimuli to elicit stronger neuronal responses than familiar ones. This demonstrates that some form of learning is reflected in the neuronal responses of these neostriatal cells. 6. Cells recorded in cortical area TF were also visually responsive, and many responded selectively to different visual stimuli. In contrast to the ventrocaudal neostriatum, however, responses of a subpopulation of cells in area TF did appear to be influenced by the reward contingencies of the task. That is, some cells responded either preferentially, or even exclusively, to the positive stimuli in the task, a preference that developed within a few trials as the animal learned to discriminate new pairs. These neuronal responses to positive stimuli were not directly related to the motor response of the animal, because they were not present on error trials when the animal responded to the negative stimulus; nor were they directly related to the delivery of the reward, because they were time locked to the onset of the visual stimulus rather than to the reward. The results suggest that some of the mechanisms underlying the learning of stimulus-response associations may be located in the cortex itself. C1 NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. RI Brown, Verity/A-5235-2011 OI Brown, Verity/0000-0001-5762-1797 NR 45 TC 63 Z9 63 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 1995 VL 74 IS 3 BP 1083 EP 1094 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA RU952 UT WOS:A1995RU95200016 PM 7500134 ER PT J AU VALENZUELA, DM ECONOMIDES, AN ROJAS, E LAMB, TM NUNEZ, L JONES, P IP, NY ESPINOSA, R BRANNAN, CI GILBERT, DJ COPELAND, NG JENKINS, NA LEBEAU, MM HARLAND, RM YANCOPOULOS, GD AF VALENZUELA, DM ECONOMIDES, AN ROJAS, E LAMB, TM NUNEZ, L JONES, P IP, NY ESPINOSA, R BRANNAN, CI GILBERT, DJ COPELAND, NG JENKINS, NA LEBEAU, MM HARLAND, RM YANCOPOULOS, GD TI IDENTIFICATION OF MAMMALIAN NOGGIN AND ITS EXPRESSION IN THE ADULT NERVOUS-SYSTEM SO JOURNAL OF NEUROSCIENCE LA English DT Article DE NOGGIN; NEURAL INDUCER; SPEMANN ORGANIZER; NIEUWKOOP CENTER; DORSALIZATION; OLFACTORY BULB; PURKINJE CELLS ID CILIARY NEUROTROPHIC FACTOR; SPEMANN ORGANIZER; LEUKEMIA; MOUSE; MAP AB The multiple roles of noggin during dorsal fate specification in Xenopus embryos, together with noggin's ability to directly induce neural tissue, inspired an effort to determine whether a similar molecule exists in mammals. Here we describe the identification of human and rat noggin and explore their expression patterns; we also localize the human NOGGIN gene to chromosome 17q22, and the mouse gene to a syntenic region of chromosome 11. Mammalian noggin is remarkably similar in its sequence to Xenopus noggin, and is similarly active in induction assays performed on Xenopus embryo tissues. In the adult mammal, noggin is most notably expressed in particular regions of the nervous system, such as the tufted cells of the olfactory bulb, the piriform cortex of the brain, and the Purkinje cells of the cerebellum, suggesting that one of the earliest acting neural inducers also has important roles in the adult nervous system. C1 UNIV CHICAGO,DEPT MED,HEMATOL ONCOL SECT,CHICAGO,IL 60637. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. UNIV CALIF BERKELEY,DEPT MOLEC & CELL BIOL,BERKELEY,CA 94720. RP VALENZUELA, DM (reprint author), REGENERON PHARMACEUT INC,777 OLD SAW MILL RIVER RD,TARRYTOWN,NY 10591, USA. FU NCI NIH HHS [CA40046, N01-CO-74101] NR 22 TC 106 Z9 114 U1 1 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP PY 1995 VL 15 IS 9 BP 6077 EP 6084 PG 8 WC Neurosciences SC Neurosciences & Neurology GA RU108 UT WOS:A1995RU10800021 PM 7666191 ER PT J AU GALLO, V RUSSELL, JT AF GALLO, V RUSSELL, JT TI EXCITATORY AMINO-ACID RECEPTORS IN GLIA - DIFFERENT SUBTYPES FOR DISTINCT FUNCTIONS SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Review DE ASTROGLIA; OLIGODENDROGLIA; KAINATE RECEPTORS; AMPA RECEPTORS; NMDA RECEPTORS; METABOTROPIC RECEPTORS ID D-ASPARTATE RECEPTORS; RAT OPTIC-NERVE; CULTURED ASTROCYTES; GLUTAMATE RECEPTOR; CALCIUM WAVES; ACTIVATED CURRENTS; KAINATE RECEPTORS; BRAIN ASTROCYTES; CORPUS-CALLOSUM; WHITE MATTER AB It is now well established that expression of voltage- and ligand-gated ionic channels, as well as G protein-coupled receptors, is not a property unique to neurons, but is also shared by macroglial cells (astrocytes and oligodendrocytes). These glial cells can receive a variety of signals from neurons at different stages of their development, Activation of membrane receptors may affect glial cell activity, proliferation, maturation, and survival through a complex cascade of intracellular events leading to long-term changes in glial cell phenotype and functional organization, Here we review the experimental evidence for glutamate receptor expression in glial cells in culture and in situ, and the molecular and functional properties of these receptors, We also describe some experimental models that identify possible functions of glutamate receptors in glia, Now that the existence of glutamate receptors in glia has been unambiguously demonstrated, future research will have to 1) determine which receptor subtypes are expressed in macroglial cells in vivo; 2) analyze, in adequate experimental models, the short- and long-term changes produced by glutamate receptor activation in glia; and 3) establish whether these receptors play a role in neuron-glia communication in the brain, (C) 1995 Wiley-Liss, Inc. RP GALLO, V (reprint author), NICHHD,CELLULAR & MOLEC NEUROPHYSIOL LAB,BLDG 49,ROOM 5A-78,BETHESDA,MD 20892, USA. NR 66 TC 90 Z9 90 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 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD SEP 1 PY 1995 VL 42 IS 1 BP 1 EP 8 DI 10.1002/jnr.490420102 PG 8 WC Neurosciences SC Neurosciences & Neurology GA RT201 UT WOS:A1995RT20100001 PM 8531218 ER PT J AU WEEKS, BS LIEBERMAN, DM JOHNSON, B ROQUE, E GREEN, M LOEWENSTEIN, P OLDFIELD, EH KLEINMAN, HK AF WEEKS, BS LIEBERMAN, DM JOHNSON, B ROQUE, E GREEN, M LOEWENSTEIN, P OLDFIELD, EH KLEINMAN, HK TI NEUROTOXICITY OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TAT TRANSACTIVATOR TO PC12 CELLS REQUIRES THE TAT AMINO-ACID-49-58 BASIC DOMAIN SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE NEUROTOXICITY; HIV-1; TAT; PC12 CELLS ID AIDS DEMENTIA COMPLEX; NERVOUS-SYSTEM; HIV-1 INFECTION; PROTEIN; IDENTIFICATION; BRAINS; BINDING AB The acquired immunodeficiency syndrome (AIDS) frequently involves the central nervous system (CNS) and manifests as dementia due to encephalitis or diffuse neurodegeneration. Human immunodeficiency virus type 1 (HIV-1) proteins, potentially transported into the CNS by mononuclear inflammatory cells, have been implicated in the etiology of this HIV-1 associated neurological dysfunction, Here we investigate the neurotoxicity of the essential HIV-1 regulator protein Tat in vivo after microinfusion into the rat brain and in vitro using PC12, NG108-15, and GT17 neuronal cell lines, Infusion of either chemically synthesized Tat (Tat86) or recombinant Tat (rTat) into the striatal gray matter in Sprague-Dawley rats resulted in postural deviation ipsilateral to the infusion, a clinical presentation in rats associated with complete striatal dysfunction, Histologic examination 3 days after infusion revealed massive necrosis in the area of the distribution of the infusion, Infusion of heat denatured rTat, peptide Tat49-58, or peptide Tat57-86 did not result in clinically or histologically detectable brain damage, After 3 days incubation in vitro, the lethal dose for half (LD50) of PC12 cells due to rTat was 5 mu g/ml, The LD50 for Tat86 under the same conditions was 10 mu g/ml. Tat49-58 and Tat57-86 peptides were not toxic in vitro even at 10-fold higher doses, At 5 mu g/ml, rTat was toxic to 100% of GT17 cells after 24 hr, At 5 mu g/ml, Tat86 was toxic to 90% of the NG108-15 cells after 7 days of treatment, Prior experiments have shown Tat49-58 is specifically recognized by a cell surface protein that mediates Tat uptake. Here we show that Tat toxicity is inhibited by cotreatment with excess Tat49-58, suggesting Tat neurotoxicity requires binding to its surface ligand, Chloroquine, which increases nuclear accumulation of Tat, enhances Tat toxicity to PC12 cells, suggesting that Tat internalization is a required step in the mechanism of its toxicity. (C) 1995 Wiley-Liss, Inc. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. ST LOUIS UNIV,HLTH SCI CTR,INST MOLEC VIROL,ST LOUIS,MO 63103. NR 30 TC 63 Z9 63 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD SEP 1 PY 1995 VL 42 IS 1 BP 34 EP 40 DI 10.1002/jnr.490420105 PG 7 WC Neurosciences SC Neurosciences & Neurology GA RT201 UT WOS:A1995RT20100004 PM 8531224 ER PT J AU ANDERSON, DH GUERIN, CJ HAGEMAN, GS PFEFFER, BA FLANDERS, KC AF ANDERSON, DH GUERIN, CJ HAGEMAN, GS PFEFFER, BA FLANDERS, KC TI DISTRIBUTION OF TRANSFORMING GROWTH-FACTOR-BETA ISOFORMS IN THE MAMMALIAN RETINA SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE GROWTH FACTORS; RETINAL PIGMENTED EPITHELIUM; PHOTORECEPTORS; MUELLER CELLS ID RAT-BRAIN; EPITHELIAL-CELLS; NERVOUS-SYSTEM; MESSENGER-RNA; TGF-BETA; LOCALIZATION; FACTOR-BETA-1; ANTIBODIES; HYPOXIA; GROWTH-FACTOR-BETA-1 AB The distribution of transforming growth factor-beta (TGF-beta) was examined in the posterior segment of the monkey, human, and feline eye using antisera to TGF-beta 1, TGF-beta 2, or TGF-beta 3. A number of different antibodies, tissue processing methods, immunolocalization techniques, and microscopic imaging systems were used in an attempt to gain a more comprehensive picture of TGF-beta isoform distribution in the retina and retinal pigmented epithelium (RPE), The results are generally consistent in identifying one or more of the three TGF-beta isoforms in the cytoplasm of a small, overlapping subset of cells, RPE cells, photoreceptors, Mueller cells, ganglion cells, hyalocytes, and cells associated with choroidal and retinal vessels are all represented in this immunoreactive population, No evidence of extracellular labeling was noted, The intracellular distribution of the three isoforms is distinctly different in photoreceptors. Anti-TGF-beta 1 precursor and anti-TGF-beta 2 immunoreactivity is confined primarily to rod outer segments, whereas anti-TGF-beta 3 immunoreactivities are restricted to mitochondria within inner segments, In the RPE, dusters of anti-TGF-beta 2 positive cytoplasmic granules are located near the cells' lateral borders, whereas anti-TGF-beta 3 labeling is concentrated apically. These results provide baseline information from which new hypotheses regarding the function(s) of TGF-beta isoforms in the retina can be formulated. (C) 1995 Wiley-Liss, Inc. C1 HENRY FORD HOSP,EYE CARE SERV,DETROIT,MI 48202. ST LOUIS UNIV,SCH MED,ANHEUSER BUSCH EYE INST,ST LOUIS,MO. AMER CYANAMID CO,STORZ OPHTHALM DIV,PEARL RIVER,NY 10965. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. RP ANDERSON, DH (reprint author), UNIV CALIF SANTA BARBARA,NEUROSCI RES INST,SANTA BARBARA,CA 93106, USA. NR 41 TC 40 Z9 41 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD SEP 1 PY 1995 VL 42 IS 1 BP 63 EP 79 DI 10.1002/jnr.490420108 PG 17 WC Neurosciences SC Neurosciences & Neurology GA RT201 UT WOS:A1995RT20100007 PM 8531227 ER PT J AU RILEY, LA HITRI, A BERNSTEIN, JJ AF RILEY, LA HITRI, A BERNSTEIN, JJ TI ASSOCIATION OF NERVE GROWTH-FACTOR MESSENGER-RNA LEVELS WITH MK-801-INDUCED EXPLOSIVE BEHAVIORS IN MICE SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE POPPING; BEHAVIOR; MK-801; MOUSE; NERVE GROWTH FACTOR; MESSENGER-RNA ID MESSENGER-RNAS; NEUROTROPHIC FACTOR; RAT HIPPOCAMPUS; NMDA ANTAGONIST; MK-801; INJECTION; NEURONS; BRAIN; ANTICONVULSANT; RECEPTORS AB MK-801, a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, stimulated an outbred strain of NIH Swiss mice to display discrete episodes of explosive jumping behavior, designated as ''popping,'' The rapid onset of the MK-801-induced ''popping'' seems to follow the rapid distribution of the drug to the frontal cortex, the area that contains high levels of NMDA receptors, We examined the effect of this drug on the levels of mRNA coding for nerve growth factor (NGF) in the frontal cortex in relation to the exhibited ''popping'' episodes, Mice treated with 1 mg/kg MK-801 could be split into two groups based on the total number of ''popping'' episodes in a 30 min post-injection period, These groups also differed in the steady-state levels of frontal cortex NGF mRNA, Animals that exhibited low numbers of ''popping'' had levels of NGF mRNA significantly higher than saline treated controls or mice that exhibited high numbers of ''popping.'' Mice treated with 10 mg/kg MK-801 had a high frequency of ''popping'' that was impossible to separate into episodes, In addition, these mice had levels of frontal cortex NGF mRNA that were significantly lower than either group of mice treated with 1 mg/kg MK-801, These data indicated that there was an increased level of NGF mRNA under conditions where MK-801 induced a low level of ''popping'' behavior, However, when ''popping'' intensified, NGF mRNA levels were decreased, suggesting a possible behavioral antagonism of the NGF response. (C) 1995 Wiley-Liss, Inc. C1 DEPT VET AFFAIRS MED CTR,NIDA RES,WASHINGTON,DC 20422. RP RILEY, LA (reprint author), DEPT VET AFFAIRS MED CTR,CNS INJURY & REGENERAT LAB,50 IRVING ST 151Q,WASHINGTON,DC 20422, USA. FU ONDIEH CDC HHS [RA-ND-90-10] NR 27 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 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD SEP 1 PY 1995 VL 42 IS 1 BP 80 EP 84 DI 10.1002/jnr.490420109 PG 5 WC Neurosciences SC Neurosciences & Neurology GA RT201 UT WOS:A1995RT20100008 PM 8531228 ER PT J AU HOLTZCLAW, LA GALLO, V RUSSELL, JT AF HOLTZCLAW, LA GALLO, V RUSSELL, JT TI AMPA RECEPTORS SHAPE CA2+ RESPONSES IN CORTICAL OLIGODENDROCYTE PROGENITORS AND CG-4 CELLS SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Note DE O-2A PROGENITORS; GLUTAMATE RECEPTORS; GYKI 52466; CYDOTHIAZIDE ID NMDA GLUTAMATE RECEPTOR; TYPE-2 ASTROCYTES; RAT; ANTIBODIES AB Intracellular calcium signals triggered by glutamate receptor activation were studied in primary cortical oligodendrocyte lineage cells and in the oligodendrocyte cell line CG-4, Glutamate, kainate, and AMPA (30-300 mu M) increased [Ca2+](i) in both types of cells at the stage of oligodendrocyte progenitors (O-2A; GD3(+)) or pro-oligodendroblasts (O4(+)). The peak amplitude of Ca2+ responses to glutamate receptor agonists was significantly larger in cortical cells. In CG-4 and in cortical cells, the majority (more than 90%) of bipolar GD3(+) or multipolar O4(+) cells responded to kainate, In all the cells analyzed, kainate was more efficacious than AMPA and glutamate, The percentage of bipolar or multipolar cells responding to glutamate was significantly lower in the CG-4 cell line than in primary cultures. Cellular responses typical of metabotropic glutamate receptor activation were observed in 20% of the cortical O-2A progenitors, but in none of the CG-4 cells, The AMPA-selective antagonist GYKI 52466 blocked kainate-induced Ca2+ responses in cortical O-2A cells, The selective AMPA receptor modulator cyclothiazide (30 mu M) greatly potentiated the effects of AMPA (30-100 mu M) on [Ca2+](i) in cortical and CG-4 cells, Our findings indicate that Ca2+ responses in cells of the oligodendrocyte lineage are primarily shaped by functional AMPA receptors. (C) 1995 Wiley-Liss, Inc. C1 NICHHD,CELLULAR & MOLEC NEUROPHYSIOL LAB,BETHESDA,MD 20892. NR 24 TC 37 Z9 37 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 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD SEP 1 PY 1995 VL 42 IS 1 BP 124 EP 130 DI 10.1002/jnr.490420114 PG 7 WC Neurosciences SC Neurosciences & Neurology GA RT201 UT WOS:A1995RT20100013 PM 8531221 ER PT J AU PHILLIPS, RL CHEN, CY WONG, DF LONDON, ED AF PHILLIPS, RL CHEN, CY WONG, DF LONDON, ED TI AN IMPROVED METHOD TO CALCULATE CEREBRAL METABOLIC RATES OF GLUCOSE USING PET SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE POSITRON EMISSION TOMOGRAPHY; CEREBRAL GLUCOSE METABOLISM; FLUORODEOXYGLUCOSE; BRAIN ID POSITRON EMISSION TOMOGRAPHY; INPUT FUNCTION; HUMAN-BRAIN; DEOXYGLUCOSE; VALIDATION; FDG AB PET methods for single-scan measurement of the cerebral metabolic rate of glucose (CMRglc) generally involve sampling of radioactivity in arterial plasma over the course of the experiment. The purpose of this study was to develop an analytic procedure that would require substantially fewer plasma samples to measure CMRglc using the single-scan method. Methods: This technique uses a model for the curve describing the time course of radioactivity in plasma. Results: This model obviates the need to draw arterial samples at short time intervals or at all during the first 30 min after radiotracer injection. The new technique uses six samples to provide the same accuracy and precision as the conventional method provides with 30 or more samples. Conclusion: The proposed method greatly simplifies quantitative PET studies of glucose metabolism. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT RADIOL,BALTIMORE,MD 21205. UNIV MARYLAND,SCH MED,DEPT PHARMACOL & EXPTL THERAPEUT,BALTIMORE,MD 21201. RP PHILLIPS, RL (reprint author), NATL INST DRUG ABUSE,ADDICT RES CTR,NEUROIMAGING & DRUG ACT SECT,INTRAMURAL RES PROGRAM,POB 5180,BALTIMORE,MD 21224, USA. NR 21 TC 24 Z9 27 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD SEP PY 1995 VL 36 IS 9 BP 1668 EP 1679 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RU095 UT WOS:A1995RU09500034 PM 7658230 ER PT J AU LINET, MS MALKER, HSR CHOW, WH MCLAUGHLIN, JK WEINER, JA STONE, BJ ERICSSON, JLE FRAUMENI, JF AF LINET, MS MALKER, HSR CHOW, WH MCLAUGHLIN, JK WEINER, JA STONE, BJ ERICSSON, JLE FRAUMENI, JF TI OCCUPATIONAL RISKS FOR CUTANEOUS MELANOMA AMONG MEN IN SWEDEN SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID BLUE-COLLAR WORKERS; MALIGNANT-MELANOMA; CANCER MORTALITY; UNITED-STATES; OUTDOOR WORK; TELECOMMUNICATIONS INDUSTRY; NEW-ZEALAND; SKIN; SHOE; MASSACHUSETTS AB A population-based linked-registry was used to evaluate incidence of malignant melanoma of the skin among Swedish men by industry and occupation. There were 3850 cutaneous melanoma cases identified in the 19-year follow-up of men employed in 1960. New associations were observed for men employed in the breweries and malt-processing industry and in shoe fabrication from leather and skins. Several findings supported associations previously reported in other countries, including an excess risk among workers in basic chemical production and the printing industry and among professional, technical, and white-collar workers. Risk overall was not increased among farmers, despite a significant excess of melanoma of the face, neck, and scalp. Although this linked registry analysis lacked information about specific agents, duration of employment, and occupational and recreational sun exposures, it did provide leads for new associations and confirmed previous ones. Nevertheless, because of these limitations, etiologic clues must be interpreted cautiously. C1 NATL BOARD OCCUPAT SAFETY & HLTH,SOLNA,SWEDEN. NATL BOARD HLTH & WELF,STOCKHOLM,SWEDEN. RP LINET, MS (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EPN 415,BETHESDA,MD 20892, USA. NR 82 TC 21 Z9 21 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD SEP PY 1995 VL 37 IS 9 BP 1127 EP 1135 DI 10.1097/00043764-199509000-00015 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RW927 UT WOS:A1995RW92700012 PM 8528722 ER PT J AU CASPERSVELU, LE WADHWANI, KC RAPOPORT, SI KADOR, PF AF CASPERSVELU, LE WADHWANI, KC RAPOPORT, SI KADOR, PF TI PERMEABILITY OF THE BLOOD-RETINAL AND BLOOD-AQUEOUS BARRIERS IN GALACTOSE-FED RATS SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Article; Proceedings Paper CT 1st Annual Meeting of the AOPT CY JAN 26-29, 1995 CL NEW ORLEANS, LA SP Assoc Ocular Pharm & Therapeut AB Blood-retinal barrier (BRB) and blood-aqueous barrier (BAB) permeability were assessed by various methods to clarify conflicting reports on whether blood-retinal barrier permeability changes occur in diabetic and galactose-fed rats and to assess the potential role of aldose reductase in this process. Different molecular weight probes were utilized in rats fed for 7-11 months either a normal diet or a diet containing 50% galactose with / without the aldose reductase inhibitor Al1576 or Ponalrestat. BRB and BAB were assessed through radiolabelled sucrose permeability studies in eyes where the anterior segment was frozen during dissection compared to eyes where the anterior segments were not frozen and by quantitative autoradiography. In addition, histological studies using Evans Blue dye, microperoxidase and horseradish peroxidase were conducted. In untreated galactose-fed rats a LF-fold increase in the mean permeability surface area product (PA) to sucrose at the BRB was observed when the aqueous humor was not frozen during retinal dissection. However, no increase in the mean PA to sucrose was observed when the aqueous humor of similar eyes was frozen during dissection. Similarly, no retinal vessel permeability increase was observed by either quantitative autoradiography of [H-3]-sucrose after 15 minutes of circulation or histological studies with microperoxidase, horseradish peroxidase or Evans Blue dye. Examination of the BAB revealed an increase in the permeability of iris vessels but not the ciliary body in galactose-fed rats which was reduced by treatment with the aldose reductase inhibitor Al1576. These data indicate that while BRB permeability is not increased in galactose-fed rats, BRB permeability measurements with isotopes are subject to possible contamination from the aqueous humor in untreated galactose-fed rats, which can result in false observations of increased BRB permeability. C1 NEI,OCULAR THERAPEUT LAB,BETHESDA,MD. NR 0 TC 10 Z9 10 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1080-7683 J9 J OCUL PHARMACOL TH JI J. Ocular Pharmacol. Ther. PD FAL PY 1995 VL 11 IS 3 BP 469 EP 487 DI 10.1089/jop.1995.11.469 PG 19 WC Ophthalmology; Pharmacology & Pharmacy SC Ophthalmology; Pharmacology & Pharmacy GA RR882 UT WOS:A1995RR88200030 PM 8590278 ER PT J AU STRATAKIS, CA MITSIADES, NS CHROUSOS, GP OCONNELL, A AF STRATAKIS, CA MITSIADES, NS CHROUSOS, GP OCONNELL, A TI RECURRING ORAL GIANT-CELL LESION IN A CHILD WITH X-LINKED HYPOPHOSPHATEMIC RICKETS - CLINICAL MANIFESTATION OF OCCULT PARATHYROIDISM SO JOURNAL OF PEDIATRICS LA English DT Note ID VITAMIN-D; PHOSPHATE; THERAPY; OSTEOMALACIA AB A 9-year-old boy with X-linked hypophosphatemic rickets had a recurring oral giant cell lesion, These lesions are relatively uncommon in children and represent a potentially aggressive disorder that is microscopically indistinguishable from the brown tumors of hyperparathyroidism. Subclinical hyperparathyroidism is not uncommon in X-linked hypophosphatemic rickets and may account for the giant cell lesion in this patient. C1 GEORGETOWN UNIV, CHILDRENS MED CTR, DIV GENET, WASHINGTON, DC 20007 USA. NIDR, CLIN INVEST & PATIENT CARE BRANCH, BETHESDA, MD 20892 USA. RP STRATAKIS, CA (reprint author), NICHHD, DEV ENDOCRINOL BRANCH,PEDIAT ENDOCRINOL SECT, 9000 ROCKVILLE PIKE,BLDG 10, ROOM 10 N 262, BETHESDA, MD 20892 USA. OI O'Connell, Anne C/0000-0002-1495-3983 NR 14 TC 5 Z9 5 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD SEP PY 1995 VL 127 IS 3 BP 444 EP 446 DI 10.1016/S0022-3476(95)70081-1 PG 3 WC Pediatrics SC Pediatrics GA RT738 UT WOS:A1995RT73800021 PM 7658280 ER PT J AU SIDRANSKY, E GINNS, EI AF SIDRANSKY, E GINNS, EI TI GENETIC-BASIS OF GAUCHER DISEASE SO JOURNAL OF PEDIATRICS LA English DT Letter RP SIDRANSKY, E (reprint author), NIMH, CLIN NEUROSCI BRANCH, BETHESDA, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD SEP PY 1995 VL 127 IS 3 BP 510 EP 510 DI 10.1016/S0022-3476(95)70104-4 PG 1 WC Pediatrics SC Pediatrics GA RT738 UT WOS:A1995RT73800037 PM 7658291 ER PT J AU DEMULDER, EK TARULLO, LB KLIMESDOUGAN, B FREE, K RADKEYARROW, M AF DEMULDER, EK TARULLO, LB KLIMESDOUGAN, B FREE, K RADKEYARROW, M TI PERSONALITY-DISORDERS OF AFFECTIVELY ILL MOTHERS - LINKS TO MATERNAL-BEHAVIOR SO JOURNAL OF PERSONALITY DISORDERS LA English DT Article ID DEPRESSION; CHILDREN; STATE; PERCEPTIONS; DIAGNOSIS; ANXIETY AB The objective of the present study was to assess relations between depression and personality disorders, and to examine how psychiatric problems are linked to maternal caretaking behavior, Subjects were affectively ill and well mothers and their children from 89 families participating in a longitudinal study of child development and childrearing, Psychiatric and behavioral measures were obtained at three time periods: when the child was a toddler, early school age, and preadolescent, A personality disorder assessment of the mother was made at the third time period, Affectively ill mothers reported more personality disorder symptoms than did well mothers, Severity of affective illness and recency of episodes were related to higher rates of personality disorder symptoms, The behavior of affectively ill mothers in interaction with their children was related to mothers' personality disorder symptoms. For example, unipolar mothers reporting higher rates of symptoms in the paranoid, schizoid, or schizotypal disorder categories (categories that are particularly indicative of interpersonal impairments) were less engaged and involved in interaction with their children, On the other hand, bipolar mothers' high level of engagement was related to higher rates of symptoms in the dependent and borderline personality disorder categories. Results demonstrate the importance of considering multiple sources of psychiatric impairment in assessing potential risks to the parent-child relationship. C1 NIMH,DEV PSYCHOL LAB,BETHESDA,MD 20892. NR 31 TC 16 Z9 16 U1 2 U2 8 PU GUILFORD PRESS PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 SN 0885-579X J9 J PERS DISORD JI J. Pers. Disord. PD FAL PY 1995 VL 9 IS 3 BP 199 EP 212 PG 14 WC Psychiatry SC Psychiatry GA RV100 UT WOS:A1995RV10000003 ER PT J AU ACS, G PALKOVITS, M BLUMBERG, PM AF ACS, G PALKOVITS, M BLUMBERG, PM TI TRIFLUOPERAZINE MODULATES [H-3] RESINIFERATOXIN BINDING BY HUMAN AND RAT VANILLOID (CAPSAICIN) RECEPTORS AND AFFECTS CA-45 UPTAKE BY ADULT-RAT DORSAL-ROOT GANGLION NEURONS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTOR; PAINFUL DIABETIC NEUROPATHY; TOPICAL CAPSAICIN; RESINIFERATOXIN BINDING; HIGH-AFFINITY; NONCOMPETITIVE BLOCKERS; POSTHERPETIC NEURALGIA; H-3 CHLORPROMAZINE; SENSORY NEURONS; SIGMA-RECEPTORS AB Optimum treatment of neuropathic pain includes the use of adjuvant analgesics such as antipsychotic drugs and tricyclic antidepressants. Although the mechanism of their analgesic action is not known, it is possible that such agents act directly on pain pathways. The ability of capsaicin and its analogs to selectively deactivate primary afferent neurons provides a basis for their use in human therapy to relieve a number of chronic pain conditions. We examined whether the phenothiazine antipsychotic drug trifluoperazine (TFP) as well as other neuroleptics and tricyclic antidepressants have an effect on the agonist binding properties and the activation of the human and rat vanilloid receptors. Binding of [H-3]resiniferatoxin (RTX) to membrane preparations of human dorsal horn and rat whole spinal cord was affected by TFP in a biphasic fashion, with an initial 25 and 65% enhancement of [H-3]RTX binding, respectively, preceding inhibition. The apparent K-i values for inhibition were 3.93 +/- 0.13 mu M for human dorsal horn and 7.91 +/- 0.62 mu M for rat spinal cord. Scatchard analyses revealed that TFP affected both the affinity and the cooperativity of [H-3]RTX binding by the receptors, leaving the receptor density unaltered. Similar effects on [H-3]RTX binding to rat spinal cord membranes were also induced by other antipsychotic phenothiazines and other types of antipsychotics, by phenothiazines without antipsychotic actions, as well as by tricyclic antidepressants. In cultures of dorsal root ganglion neurones, TFP at concentrations that increased [H-3]RTX binding (1-3 mu M) also induced an increase in Ca-45 uptake; this increase was absent in cultures prepared from capsaicin desensitized animals. Furthermore, TFP at a concentration of 10 mu M also increased the extent of Ca-45 uptake induced by 0.3 mu M capsaicin. Our results suggest that at therapeutic concentrations (0.5-5.0 mu M) TFP may increase the affinity of the vanilloid receptor for agonists and thereby accelerate its desensitization. C1 NIMH,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,MOLEC MECHANISMS TUMOR PROMOT SECT,BETHESDA,MD 20892. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RP ACS, G (reprint author), NCI,LCCTP,MMTP,BLDG 37-3B25,BETHESDA,MD 20892, USA. RI Palkovits, Miklos/F-2707-2013 NR 73 TC 21 Z9 21 U1 1 U2 4 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 SEP PY 1995 VL 274 IS 3 BP 1090 EP 1098 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RV893 UT WOS:A1995RV89300009 PM 7562474 ER PT J AU CIUFFO, GM SAAVEDRA, JM AF CIUFFO, GM SAAVEDRA, JM TI SELECTIVE PEPTIDE AND NONPEPTIDE LIGANDS DIFFERENTIALLY BIND TO ANGIOTENSIN-II AT(2) RECEPTOR AND A NON-ANGIOTENSIN-II CGP42112 BINDING-SITE SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SUBTYPES; BRAIN; RAT; ANTAGONISTS; SERIES AB [I-125]CGP42112 [Nic-Tyr-(epsilon-CBZ (benzyloxycarbonyl)-Arg)Lys-His-Pro-IIe] does not only recognize angiotensin II AT(2) receptors, but has also the capacity to label a high-affinity, non-angiotensin II binding site, selectively associated with macrophages and activated microglia. We have searched for the structural requirements of the novel CGP42112 binding site, and compared these with the requirements for binding to the angiotensin II AT(2) site. We designed a series of CGP42112 analogs and evaluated the new compounds by using binding assays on rat spleen (CGP42112 site) and rat fetal (angiotensin II AT(2) site) membranes. The nonpeptidic analog Z-Arg(Pmc)OH(N(alpha)CBZ-N-G-2,2;5,7,8-pentamet ylchroman-6-sulphonyl-L-Arg), the side chain of CGP42112 substituted on the guanidinium group, was selective in recognizing the CGP42112 site, and did not displace binding from the angiotensin II A(2) site. This is a potential lead compound for development of CGP42112 site-selective analogs. Conversely, the CGP42112 analog lacking the CBZ-group (Nic-Tyr-(Ac-Arg)Lys-His-ProOH, III) and the peptide Nic-Tyr-Lys-His-Ala-HisOH (VI), were selective for the angiotensin II AT(2) site, and recognized the CGP42112 site poorly. Our results demonstrate that the structural requirements for the nonangiotensin II CGP42112 and the angiotensin II AT(2) binding sites are different. We propose that the CBZ group and the free carboxyl terminal group, together with their spatial orientation, are key components of the molecule for the interaction in the non-angiotensin CGP42112 binding pocket. RP CIUFFO, GM (reprint author), NIMH,CLIN SCI LAB,PHARMACOL SECT,BLDG 10,ROOM 2D-45,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 24 TC 9 Z9 9 U1 0 U2 1 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 SEP PY 1995 VL 274 IS 3 BP 1129 EP 1134 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RV893 UT WOS:A1995RV89300014 PM 7562479 ER PT J AU PRITCHARD, JB AF PRITCHARD, JB TI INTRACELLULAR ALPHA-KETOGLUTARATE CONTROLS THE EFFICACY OF RENAL ORGANIC ANION TRANSPORT SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID BASOLATERAL MEMBRANE-VESICLES; ACID-BASE ALTERATIONS; STIMULATES PAH UPTAKE; RAT-KIDNEY; PARA-AMINOHIPPURATE; PROXIMAL TUBULE; NET SECRETION; LIVER-CELLS; SODIUM; RABBIT AB Renal organic anion secretion is driven by indirect coupling to the Na+ gradient at the basolateral membrane through Na+-dicarboxylate cotransport and dicarboxylate-organic anion exchange. The impact of changing intracellular alpha-ketoglutarate (alpha KG) concentrations and gradient on p-aminohippurate (PAH) transport was assessed in rat renal cortical slices. Fluorimetric analysis of alpha KG indicated that freshly isolated slices averaged 137 +/- 4 nmol/g wet weight (similar to 265 mu M in cellular water). This value was sustained over several hours at 4 degrees C. On incubation at 22 degrees C, intracellular alpha KG concentrations rose steadily, reaching levels of 2 (air) to 4 (100% O-2) times that of fresh tissue. When internal alpha KG was increased by preincubation and PAH uptake was determined at a fixed gradient, PAH transport increased with increasing internal alpha KG. Conversely, at a fixed internal alpha KG concentration, PAH uptake was a linear function of the driving force provided by the alpha KG gradient. Thus, intracellular alpha KG is a major determinant of the efficacy of renal organic anion transport, and events that alter internal alpha KG concentration, gradient, or both are poised to exert significant control over organic anion secretion. Kinetic analysis of alpha KG-PAH exchange indicated that the K-m, for alpha KG was 151 mu M in basolateral membrane vesicles and 131 mu M in slices. Because PAH transport increased at intracellular alpha KG concentrations that should have been saturating, this finding indicates that cytoplasmic alpha KG levels must be substantially lower than total tissue concentration, i.e., that much intracellular alpha KG must be sequestered. RP PRITCHARD, JB (reprint author), NIEHS,CELLULAR & MOLEC PHARMACOL LAB,COMPARAT MEMBRANE PHARMACOL SECT,MAIL DROP 19-01,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 47 TC 56 Z9 57 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 SEP PY 1995 VL 274 IS 3 BP 1278 EP 1284 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RV893 UT WOS:A1995RV89300034 PM 7562499 ER PT J AU BELCHEVA, MM GUCKER, S CHUANG, DM CLARK, WG JEFCOAT, LB MCHALE, RJ TOTH, G BORSODI, A COSCIA, CJ AF BELCHEVA, MM GUCKER, S CHUANG, DM CLARK, WG JEFCOAT, LB MCHALE, RJ TOTH, G BORSODI, A COSCIA, CJ TI MODULATION OF OPIOID BINDING ASSOCIATED WITH NUCLEAR MATRIX AND NUCLEAR-MEMBRANES OF NG108-15 CELLS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ADENOSINE 3'-5'-CYCLIC MONOPHOSPHATE; INDUCED DOWN-REGULATION; HYBRID-CELLS; COUPLED RECEPTORS; AGONIST BINDING; PERTUSSIS TOXIN; LIGAND-BINDING; DNA-BINDING; EXPRESSION; PROTEINS AB Opioid binding sites were found in nuclear matrix preparations from NG108-15 neurohybrid cells. Binding parameters of delta-specific radioligands indicated that high-affinity binding sites discovered in purified nuclei were present in nuclear membranes and nuclear matrix fractions. Agonists bind with low affinity, if at all, to nuclear matrix preparations. Neither sensitivity of agonist binding to the GTP analog 5-guanylylimido-diphosphate nor adenylyl cyclase activity were detected in this fraction, suggesting the presence of guanine nucleotide binding regulatory protein/effector uncoupled sites. Opioid inhibition of basal and forskolin-stimulated adenylyl cyclase activity was found in nuclear membrane preparations. Cycloheximide treatment of cells inhibited opioid binding to nuclear membrane fractions to a greater extent than that associated with membranes sedimenting at 20,000 x g (P-20) or nuclear matrix. Colchicine, a microtubule disrupter and inhibitor of receptor internalization, caused up-regulation of nuclear membrane and P-20 opioid receptors and a loss in nuclear matrix associated sites. Taxol, a microtubule stabilizing agent, prevented the effect of colchicine. Etorphine-elicited down-regulation increased nuclear matrix associated binding while diminishing that in nuclear membranes and P-20 fractions. Agonist-induced desensitization completely abolished nuclear matrix binding. In vitro preincubation of nuclear matrix preparations with protein kinase A catalytic subunit mimicked the desensitization effect. Forskolin treatment of cells potentiated nuclear matrix and P-20 binding. These data suggest that nuclear membrane opioid receptors represent newly synthesized molecules en route to the cell surface, whereas nuclear matrix contains internalized delta sites. C1 ST LOUIS UNIV,SCH MED,EA DOISY DEPT BIOCHEM & MOLEC BIOL,ST LOUIS,MO 63104. NIMH,BETHESDA,MD 20892. BIOL RES CTR,H-6701 SZEGED,HUNGARY. RI Bohn, Laura/A-4412-2008; Bohn, Laura/A-7483-2014 OI Bohn, Laura/0000-0002-6474-8179 NR 37 TC 18 Z9 18 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 1995 VL 274 IS 3 BP 1513 EP 1523 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RV893 UT WOS:A1995RV89300063 PM 7562528 ER PT J AU KOBAYASHI, S KISHI, H YOSHIHARA, A HORII, K TSUTSUI, A HIMENO, T HOROWITZ, AM AF KOBAYASHI, S KISHI, H YOSHIHARA, A HORII, K TSUTSUI, A HIMENO, T HOROWITZ, AM TI TREATMENT AND POSTTREATMENT EFFECTS OF FLUORIDE MOUTHRINSING AFTER 17 YEARS SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article DE FLUORIDE MOUTHRINSE; TREATMENT POSTTREATMENT BENEFITS AB Objectives: This study assessed the treatment and posttreatment effects of a school-based, fluoride mouthrinse regimen. Methods: Children in a nonfluoridated community in Japan participated in a daily rinse program using a 0.05 percent NaF solution in nursery and primary schools, and a weekly rinse with 0.2 percent NaF in junior high school. Students were examined at least annually for dental caries and dental treatment was provided in a public dental clinic through the ninth grade. Incipient carious lesions with no cavitation were not restored. Results: The percent of children in grades one through nine (6-14 years of age) with caries-free permanent teeth increased from 13.4 percent in 1974 to 73.0 percentin 1991, while the mean DMFT decreased by 86 percent during this period. For 12-year-olds, mean DMFT scores declined to about one tooth per child after 1982. For adults 20 years of age, there was a 64 percent difference in DMFS between the treatment group who started the rinse regimen at 4 years of age and continued for 11 years, and the controls who lived in different districts and did not participate in a fluoride rinse regimen. Conclusions: Children who began rinsing at 4 or 5 years of age benefited the most from the program. The program was inexpensive, simple to implement and well accepted by families and teachers. The conservative treatment policy in the public clinic likely contributed to the benefits derived by participants. C1 FUKUOKA DENT COLL,DEPT PREVENT DENT,FUKUOKA,JAPAN. MAKI MURA NATL INSURANCE CLIN,DENT OFF,NIIGATA,JAPAN. NIDR,BETHESDA,MD. RP KOBAYASHI, S (reprint author), NIIGATA UNIV,SCH DENT,DEPT PREVENT DENT,2 BAN CHO GAKKOCHO DORI,NIIGATA 951,JAPAN. NR 20 TC 16 Z9 16 U1 1 U2 2 PU AAPHD NATIONAL OFFICE PI RICHMOND PA J PUBLIC HEALTH DENT 10619 JOUSTING LANE, RICHMOND, VA 23235 SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD FAL PY 1995 VL 55 IS 4 BP 229 EP 233 DI 10.1111/j.1752-7325.1995.tb02374.x PG 5 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA TB173 UT WOS:A1995TB17300007 PM 8551462 ER PT J AU KNATTERUD, GL BOURASSA, MG PEPINE, CJ AF KNATTERUD, GL BOURASSA, MG PEPINE, CJ TI EFFECTS OF TREATMENT STRATEGIES TO SUPPRESS ISCHEMIA IN PATIENTS WITH CORONARY-ARTERY DISEASE - 12-WEEK RESULTS OF THE ASYMPTOMATIC CARDIAC ISCHEMIA PILOT (ACIP) STUDY (VOL 24, PG 11, 1994) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Correction, Addition C1 NHLBI,BETHESDA,MD 20892. RP KNATTERUD, GL (reprint author), AMER COLL CARDIOL,CTR CLIN COORDINATING,BETHESDA,MD 20814, USA. NR 1 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP PY 1995 VL 26 IS 3 BP 842 EP 842 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RR070 UT WOS:A1995RR07000046 ER PT J AU YOUNG, DR SHARP, DS PETROVITCH, H CURB, JD AF YOUNG, DR SHARP, DS PETROVITCH, H CURB, JD TI INTERNAL VALIDITY OF THE PHYSICAL-ACTIVITY INDEX OVER 26 YEARS IN MIDDLE-AGED AND OLDER MEN SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID FORMER COLLEGE-STUDENTS; CORONARY HEART-DISEASE; LIPOPROTEIN LEVELS; RISK; EXERCISE; PROGRAM AB OBJECTIVE: To determine the internal validity of the physical activity index (PAI). DESIGN: Three time periods over a 26-year period (1965/68 examination, n = 7911; 1980/82 examination, n = 2054; 1991/93 examination, n = 3425). SETTING: Honolulu, Hawaii. PARTICIPANTS: Middle-aged to older Japanese-American men. MEASUREMENTS: PAI, other physical activity measures, body mass index (BMI), tricep skinfold thickness, subscapular skinfold thickness, and HDL cholesterol. RESULTS: PAI level was associated significantly with levels of other physical activity measures at all time periods. Higher PAI level was associated with lower BMI at the baseline examination (1965/68), lower subscapular skinfold thickness at the 1965/68 and 1980/82 examinations, lower tricep skinfold thickness at all examinations, and higher HDL cholesterol at the 1980/82 examination. Change in PAI level from 1965/68 to 1980/82 was associated with change in BMI, subscapular, and tricep skinfold thickness levels, but there were no significant associations between change in PAI level and change in BMI, skinfold thicknesses, or HDL cholesterol levels from 1980/82 to 1991/93. CONCLUSION: PAI level is a relatively valid estimate of overall daily energy expenditure that may be an acceptable general measure across the middle-to-late stages of life. The PAI may also be sensitive enough to discern a shift toward less physical demanding activities as a population becomes older, although further studies should be conducted to better determine its validity in older populations. C1 UNIV HAWAII MANOA,JOHN A BURNS SCH MED,DIV GERIATR MED,HONOLULU,HI 96822. NHLBI,HONOLULU HEART PROGRAM,HONOLULU,HI. KUAKINI MED CTR,HONOLULU HEART PROGRAM,HONOLULU,HI. NR 26 TC 8 Z9 8 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1995 VL 43 IS 9 BP 999 EP 1006 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA RT908 UT WOS:A1995RT90800008 PM 7657940 ER PT J AU OCONNOR, KG HARMAN, SM BELLANTONI, MF STEVENS, TE PABST, K COTTRELL, E BLACKMAN, MR AF OCONNOR, KG HARMAN, SM BELLANTONI, MF STEVENS, TE PABST, K COTTRELL, E BLACKMAN, MR TI EFFECTS OF GH, IGF-I, AND BODY-FAT ON MARKERS OF BONE METABOLISM IN HEALTHY ELDERLY PERSONS SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. JOHNS HOPKINS MED INST,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1995 VL 43 IS 9 BP SA24 EP SA24 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA RT908 UT WOS:A1995RT90800126 ER PT J AU WALSTON, J SILVER, K BOGARDUS, C KNOWLER, WC AUSTIN, SA SORKIN, J ROTH, J SHULDINER, A AF WALSTON, J SILVER, K BOGARDUS, C KNOWLER, WC AUSTIN, SA SORKIN, J ROTH, J SHULDINER, A TI NEW INVESTIGATOR AWARDEE MISSENSE MUTATION IN THE BETA-3-ADRENERGIC RECEPTOR GENE IN MIDDLE-AGED IN ELDERLY PIMA-INDIANS AND ITS RELATIONSHIP TO OBESITY AND NIDDM SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21218. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1995 VL 43 IS 9 BP SA9 EP SA9 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA RT908 UT WOS:A1995RT90800063 ER PT J AU DIGIOVANNI, SR ECELBARGER, C TERRIS, J KNEPPER, MA AF DIGIOVANNI, SR ECELBARGER, C TERRIS, J KNEPPER, MA TI REGULATION OF VASOPRESSIN V2 RECEPTOR PROTEIN EXPRESSION IN RAT-KIDNEY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 VIRGINIA COMMONWEALTH UNIV,RICHMOND,VA. NHLBI,LKEM,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 320 EP 320 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600072 ER PT J AU KISHORE, BK TERRIS, J KNEPPER, MA AF KISHORE, BK TERRIS, J KNEPPER, MA TI QUANTIFICATION OF AQUAPORIN-2 PROTEIN IN MICRODISSECTED RAT RENAL TUBULE SEGMENTS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 324 EP 324 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600088 ER PT J AU KISHORE, BK MANDON, B OZA, NB DIGIOVANNI, S COLEMAN, RA WADE, JB KNEPPER, MA AF KISHORE, BK MANDON, B OZA, NB DIGIOVANNI, S COLEMAN, RA WADE, JB KNEPPER, MA TI THE RAT RENAL ARCADE SEGMENT IS A SITE OF EXPRESSION OF THE V2 VASOPRESSIN RECEPTOR AND THE VASOPRESSIN-REGULATED WATER CHANNEL SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. UNIV MARYLAND,BALTIMORE,MD 21201. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 325 EP 325 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600089 ER PT J AU MARPLES, D DORUP, J KNEPPER, MA NIELSEN, S AF MARPLES, D DORUP, J KNEPPER, MA NIELSEN, S TI HYPOKALEMIA-INDUCED DOWN-REGULATION OF AQUAPORIN-2 WATER CHANNEL EXPRESSION IN RAT-KIDNEY MEDULLA AND CORTEX SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 AARHUS UNIV,AARHUS,DENMARK. NHLBI,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 325 EP 325 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600091 ER PT J AU NIELSEN, S TERRIS, J HEDIGER, M ECELBARGER, CA KNEPPER, MA AF NIELSEN, S TERRIS, J HEDIGER, M ECELBARGER, CA KNEPPER, MA TI IMMUNO-LOCALIZATION OF THE VASOPRESSIN-REGULATED UREA TRANSPORTER (UT2) IN RAT-KIDNEY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 AARHUS UNIV,AARHUS,DENMARK. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. HARVARD UNIV,BOSTON,MA 02115. NHLBI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 327 EP 327 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600097 ER PT J AU OLSON, BR ELLIOT, SJ KNEPPER, MA VERBALIS, JG AF OLSON, BR ELLIOT, SJ KNEPPER, MA VERBALIS, JG TI ROLE OF LONG-TERM REGULATION OF AQUAPORIN-2 WATER CHANNEL EXPRESSION IN VASOPRESSIN ESCAPE AND CHLORPROPAMIDE-INDUCED ANTIDIURESIS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NICHHD,DEB,BETHESDA,MD. NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. GEORGETOWN UNIV,DIV ENDOCRINOL,WASHINGTON,DC. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 327 EP 327 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600099 ER PT J AU SMITH, CP SHAYAKUL, C YOU, GF MARTIAL, S LEE, WS MACKENZIE, HS SANDS, JM KNEPPER, MA HEDIGER, MA AF SMITH, CP SHAYAKUL, C YOU, GF MARTIAL, S LEE, WS MACKENZIE, HS SANDS, JM KNEPPER, MA HEDIGER, MA TI MOLECULAR CHARACTERIZATION AND REGULATION OF EXPRESSION OF THE VASOPRESSIN-REGULATED UREA TRANSPORTER SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,DIV RENAL,BOSTON,MA 02115. EMORY UNIV,ATLANTA,GA 30322. NIH,BETHESDA,MD 20892. NR 1 TC 3 Z9 3 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 329 EP 329 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600107 ER PT J AU TERRIS, J ECELBARGER, CA NIELSEN, S KNEPPER, MA AF TERRIS, J ECELBARGER, CA NIELSEN, S KNEPPER, MA TI LONG-TERM REGULATION OF 4 AQUAPORIN WATER CHANNELS IN RAT-KIDNEY - ROLES OF VASOPRESSIN AND MEDULLARY HYPERTONICITY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. AARHUS UNIV,AARHUS,DENMARK. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 330 EP 330 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600109 ER PT J AU ECELBARGER, CA WADE, JB TERRIS, J MARPLES, D NIELSEN, S KNEPPER, MA AF ECELBARGER, CA WADE, JB TERRIS, J MARPLES, D NIELSEN, S KNEPPER, MA TI LOCALIZATION AND REGULATION OF BUMETANIDE-SENSITIVE COTRANSPORTER PROTEIN IN RAT-KIDNEY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. UNIV MARYLAND,BALTIMORE,MD 21201. UNIV AARHUS,DK-8200 AARHUS,DENMARK. NR 0 TC 5 Z9 5 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 335 EP 335 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600131 ER PT J AU KOVBASNJUK, O CHATTON, JY SPRING, KR AF KOVBASNJUK, O CHATTON, JY SPRING, KR TI REGULATION OF TIGHT JUNCTION NA PERMEABILITY IN MDCK CELL MONOLAYERS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 343 EP 343 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600161 ER PT J AU FERRARIS, JD WILLIAMS, CK BURG, MB AF FERRARIS, JD WILLIAMS, CK BURG, MB TI IDENTIFICATION OF OSMOTIC RESPONSE ELEMENT(S) (ORES) IN THE RABBIT ALDOSE REDUCTASE GENE SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 360 EP 360 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600232 ER PT J AU KWON, ED ZABLOCKI, K PETERS, EM JUNG, KY GARCIAPEREZ, A BURG, MB AF KWON, ED ZABLOCKI, K PETERS, EM JUNG, KY GARCIAPEREZ, A BURG, MB TI BETAINE (B) AND INOSITOL (I) REDUCE MDCK CELL GLYCEROPHOSPHOCHOLINE (GPC) BY STIMULATING ITS DEGRADATION SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 364 EP 364 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600247 ER PT J AU MANDON, B NIELSEN, S KNEPPER, MA AF MANDON, B NIELSEN, S KNEPPER, MA TI DISTRIBUTION OF 4 SYNTAXIN ISOFORMS IN RAT-KIDNEY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV AARHUS,DK-8200 AARHUS,DENMARK. NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 376 EP 376 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600296 ER PT J AU MARPLES, D KNEPPER, MA NIELSEN, S AF MARPLES, D KNEPPER, MA NIELSEN, S TI CYTOPLASMIC DYNEIN IS PRESENT IN RAT COLLECTING DUCTS, AND MAY MEDIATE VASOPRESSIN-INDUCED TRAFFICKING OF AQUAPORIN-2 (AQP2) WATER CHANNELS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV AARHUS,DK-8200 AARHUS,DENMARK. NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 377 EP 377 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600297 ER PT J AU NIELSEN, S MARPLES, D TRIMBLE, W DALBY, NO BIRN, H MOTASHAMI, M KNEPPER, MA AF NIELSEN, S MARPLES, D TRIMBLE, W DALBY, NO BIRN, H MOTASHAMI, M KNEPPER, MA TI COLOCALIZATION OF THE VAMP2 VESICLE-TARGETING RECEPTOR AND THE AQUAPORIN-2 WATER CHANNEL IN INTRACELLULAR VESICLES OF COLLECTING DUCTS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV AARHUS,DK-8200 AARHUS,DENMARK. NHLBI,BETHESDA,MD 20892. UNIV TORONTO,TORONTO,ON,CANADA. RI Birn, Henrik/C-3931-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 377 EP 377 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600300 ER PT J AU JONES, CA MCQUILLAN, G AGODOA, L KUSEK, J EBERHARDT, M HERMAN, W CORESH, J SALIVE, M JONES, CP AF JONES, CA MCQUILLAN, G AGODOA, L KUSEK, J EBERHARDT, M HERMAN, W CORESH, J SALIVE, M JONES, CP TI SERUM CREATININE LEVELS IN THE UNITED-STATES - PHASE-I OF THE 3RD NATIONAL-HEALTH AND NUTRITION EXAMINATION SURVEY (NHANES-3) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NCHS,HYATTSVILLE,MD. CDC,ATLANTA,GA. JOHNS HOPKINS UNIV,BALTIMORE,MD. HARVARD UNIV,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 392 EP 392 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600359 ER PT J AU LEE, JY GREENE, PG DOUGLAS, M GRIM, C KIRK, KA KUSEK, JW MILLIGAN, S SMITH, DE WHELTON, PK AF LEE, JY GREENE, PG DOUGLAS, M GRIM, C KIRK, KA KUSEK, JW MILLIGAN, S SMITH, DE WHELTON, PK TI DETERMINANTS OF MINORITY PARTICIPANT ADHERENCE IN CLINICAL-TRIALS - EXPERIENCE OF THE AFRICAN-AMERICAN STUDY OF KIDNEY-DISEASE AND HYPERTENSION (AASK) PILOT-STUDY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 395 EP 395 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600369 ER PT J AU LEVEY, AS BECK, GJ BOSCH, JP CAGGIULA, AW GREENE, T HUNSICKER, LG KLAHR, S AF LEVEY, AS BECK, GJ BOSCH, JP CAGGIULA, AW GREENE, T HUNSICKER, LG KLAHR, S TI SHORT-TERM EFFECTS OF PROTEIN-INTAKE, BLOOD-PRESSURE, AND ANTIHYPERTENSIVE THERAPY ON GFR IN THE MDRD STUDY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 395 EP 395 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600370 ER PT J AU HIRSCHMAN, G JONES, C AGODOA, L STRIKER, G AF HIRSCHMAN, G JONES, C AGODOA, L STRIKER, G TI INCIDENCE AND CAUSES OF ESRD IN CHILDREN IN THE USA SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 396 EP 396 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600375 ER PT J AU PORUSH, JG LAZARUS, JM BOURGOIGNIE, JJ BUCKALEW, VM GREENE, T MILAS, NC PARANANDI, L PETERSON, JC RAUCH, S SOUCIE, JM STOLLAR, C AF PORUSH, JG LAZARUS, JM BOURGOIGNIE, JJ BUCKALEW, VM GREENE, T MILAS, NC PARANANDI, L PETERSON, JC RAUCH, S SOUCIE, JM STOLLAR, C TI EFFICACY OF ANTIHYPERTENSIVE INTERVENTIONS IN REDUCING BLOOD-PRESSURE IN THE MDRD STUDY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 400 EP 400 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600390 ER PT J AU SOUCIE, JM SANDLER, DP MCCLELLAN, W AF SOUCIE, JM SANDLER, DP MCCLELLAN, W TI KIDNEY-STONES AS A RISK FACTOR FOR CHRONIC RENAL-DISEASE SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 EMORY UNIV,ATLANTA,GA 30322. NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 403 EP 403 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600401 ER PT J AU TOTO, R CORESH, J JONES, C KIRK, K AF TOTO, R CORESH, J JONES, C KIRK, K TI SERUM CREATININE IS MORE PRECISE THAN CREATININE CLEARANCE FOR ESTIMATING GFR IN AFRICAN-AMERICANS (AA) - RESULTS FROM THE AFRICAN-AMERICAN STUDY OF KIDNEY-DISEASE AND HYPERTENSION (AASK) PILOT-STUDY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 406 EP 406 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600413 ER PT J AU AUSTIN, HA FESSLER, BJ BOUMPAS, DT VAUGHAN, EM KLIPPEL, JH BALOW, JE AF AUSTIN, HA FESSLER, BJ BOUMPAS, DT VAUGHAN, EM KLIPPEL, JH BALOW, JE TI PROGNOSTIC INDICATORS SUPPORTING USE OF SHORT COURSES OF PULSE IMMUNOSUPPRESSION FOR SEVERE LUPUS NEPHRITIS (LN) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 411 EP 411 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600435 ER PT J AU OLSEN, BR KNEPPER, MA GOLDSMITH, P ELLIOT, SJ AF OLSEN, BR KNEPPER, MA GOLDSMITH, P ELLIOT, SJ TI URINARY AQUAPORIN-2 EXCRETION IN HUMANS - EVALUATION OF COLLECTING DUCT RESPONSIVENESS TO VASOPRESSIN SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. NICHHD,DEB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 442 EP 442 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600558 ER PT J AU PAGTALUNAN, ME MILLER, PL NELSON, RG AYERS, BD COPLON, N JUMPINGEAGLE, S MEYER, TW AF PAGTALUNAN, ME MILLER, PL NELSON, RG AYERS, BD COPLON, N JUMPINGEAGLE, S MEYER, TW TI GLOMERULAR STRUCTURE IN LONG-TERM TYPE-II DIABETES WITH AND WITHOUT MICROALBUMINURIA SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 VET AFFAIRS MED CTR,PALO ALTO,CA 94304. NIDDK,PHOENIX,AZ. STANFORD UNIV,STANFORD,CA 94305. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 454 EP 454 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600606 ER PT J AU ATHIENITES, NV MEYER, KB MARTIN, A GASSMAN, JJ LEVEY, AS AF ATHIENITES, NV MEYER, KB MARTIN, A GASSMAN, JJ LEVEY, AS TI BASE-LINE HEALTH-STATUS AND COMORBIDITY IN THE HEMO PILOT-STUDY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD. NR 1 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 518 EP 518 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600862 ER PT J AU DWYER, JT KOPPLE, JD MARONI, BJ BURROWES, JD POWERS, SN COCKRAM, DB CHUMLEA, WC KUSEK, JW MAKOFF, R CUNNIFF, PJ GOLDSTEIN, DJ PARANANDI, L AF DWYER, JT KOPPLE, JD MARONI, BJ BURROWES, JD POWERS, SN COCKRAM, DB CHUMLEA, WC KUSEK, JW MAKOFF, R CUNNIFF, PJ GOLDSTEIN, DJ PARANANDI, L TI DIETARY-INTAKE AND NUTRITIONAL-STATUS IN THE HEMO PILOT-STUDY POPULATION SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,HEMODIALYSIS STUDY,BETHESDA,MD. NR 0 TC 8 Z9 9 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 576 EP 576 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68601095 ER PT J AU DAUGIRDAS, JT DEPNER, TA GOTCH, F KESHAVIAH, P GREENE, T SCHULMAN, G LEVIN, N AF DAUGIRDAS, JT DEPNER, TA GOTCH, F KESHAVIAH, P GREENE, T SCHULMAN, G LEVIN, N TI COMPARISON OF METHODS TO PREDICT THE EQUILIBRATED KT/V(EKTV) IN THE HEMO STUDY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD. NR 1 TC 7 Z9 7 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 596 EP 596 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68601173 ER PT J AU DEPNER, TA GOTCH, F DAUGIRDAS, JT GREENE, T KAUFMAN, AM AF DEPNER, TA GOTCH, F DAUGIRDAS, JT GREENE, T KAUFMAN, AM TI MONITORING DIALYSIS THERAPY USING ESTIMATES OF AMOUNT OF UREA REMOVED AND MEAN UREA VOLUME SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,HEMODIALYSIS STUDY HEMO,BETHESDA,MD. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 597 EP 597 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68601180 ER PT J AU EKNOYAN, G BECK, GJ KUSEK, JW LEVEY, AS LEVIN, NW ORNT, DB OWEN, WF SCHULMAN, G AF EKNOYAN, G BECK, GJ KUSEK, JW LEVEY, AS LEVIN, NW ORNT, DB OWEN, WF SCHULMAN, G TI DESIGN, CHARACTERIZATION OF PREVALENT PATIENTS, AND PROGRESS OF THE HEMODIALYSIS (HEMO) STUDY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD. NR 0 TC 4 Z9 4 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 598 EP 598 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68601184 ER PT J AU LEYPOLDT, JK CHEUNG, AK AGODOA, LY DAUGIRDAS, JT AF LEYPOLDT, JK CHEUNG, AK AGODOA, LY DAUGIRDAS, JT TI DIALYZER UREA MASS TRANSFER-AREA COEFFICIENT (KOA) INCREASES AT HIGH DIALYSATE FLOW-RATE SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD. NR 0 TC 7 Z9 7 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 606 EP 606 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68601215 ER PT J AU ALBRECHT, FE DRAGO, J EISNER, GM FELDER, RA SIBLEY, DR WESTPHAL, HJ JOSE, PA AF ALBRECHT, FE DRAGO, J EISNER, GM FELDER, RA SIBLEY, DR WESTPHAL, HJ JOSE, PA TI DEVELOPMENT OF HYPERTENSION IN MUTANT MICE LACKING ONE OR BOTH D-1A RECEPTOR ALLELES SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. MONASH UNIV,CLAYTON,VIC 3168,AUSTRALIA. UNIV VIRGINIA,HLTH SCI CTR,CHARLOTTESVILLE,VA. NINCDS,BETHESDA,MD 20892. NICHHD,BETHESDA,MD. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 618 EP 618 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68601262 ER PT J AU LEE, JY SMITH, DE CORNELL, CE FAULKNER, M KOPPLE, J KUSEK, JW MILLIGAN, S AF LEE, JY SMITH, DE CORNELL, CE FAULKNER, M KOPPLE, J KUSEK, JW MILLIGAN, S TI QUALITY-OF-LIFE IN THE AFRICAN-AMERICAN STUDY OF KIDNEY-DISEASE AND HYPERTENSION (AASK) PILOT-STUDY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 644 EP 644 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68601367 ER PT J AU TALUSAN, JC SIKORSKI, I BLACKMAN, MR HARMAN, SM SPECTOR, DA AF TALUSAN, JC SIKORSKI, I BLACKMAN, MR HARMAN, SM SPECTOR, DA TI EFFECTS OF MENSTRUAL-CYCLE PHASE ON RENAL-FUNCTION IN HEALTHY WOMEN SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. JOHNS HOPKINS BAYVIEW MED CTR,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 685 EP 685 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68601531 ER PT J AU CARLSON, SG COPELAND, TD BALLERMANN, BJ AF CARLSON, SG COPELAND, TD BALLERMANN, BJ TI DEVELOPMENTAL REGULATION OF SET EXPRESSION SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. RI Ballermann, Barbara/G-5349-2016 OI Ballermann, Barbara/0000-0002-8220-6381 NR 2 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 691 EP 691 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68601556 ER PT J AU LIPSCHUTZ, JH SAMID, D CUNHA, GR AF LIPSCHUTZ, JH SAMID, D CUNHA, GR TI PHENYLACETATE IS AN INHIBITOR OF UROGENITAL GROWTH AND DEVELOPMENT SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 701 EP 701 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68601595 ER PT J AU ZAUNER, I BRAUCH, H ZBAR, B GLAVAC, D RIEGLER, P MASEK, O LIPS, CJM NEUMANN, HPH AF ZAUNER, I BRAUCH, H ZBAR, B GLAVAC, D RIEGLER, P MASEK, O LIPS, CJM NEUMANN, HPH TI GERMLINE MUTATIONS IN 25 CENTRAL-EUROPEAN FAMILIES WITH VONHIPPEL-LINDAU-SYNDROME-ASSOCIATED RENAL-CELL CARCINOMA SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV FREIBURG,DEPT MED,W-7800 FREIBURG,GERMANY. TECH UNIV MUNICH,DEPT PATHOL,W-8000 MUNICH,GERMANY. NCI,FREDERICK,MD 21701. COMMUNITY HOSP,BOLZANO,ITALY. COMMUNITY HOSP,ZLIN,CZECH REPUBLIC. UNIV UTRECHT,DEPT MED,UTRECHT,NETHERLANDS. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 716 EP 716 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68601654 ER PT J AU LIU, ZH STRIKER, GE STETLERSTEVENSON, M FUKUSHIMA, P STAHL, PD STRIKER, LJ AF LIU, ZH STRIKER, GE STETLERSTEVENSON, M FUKUSHIMA, P STAHL, PD STRIKER, LJ TI TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) AND IL-1-ALPHA INDUCE APOPTOSIS IN GLOMERULAR MESANGIAL CELLS, BUT NOT IN ENDOTHELIAL-CELLS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD. NCI,BETHESDA,MD 20892. WASHINGTON UNIV,ST LOUIS,MO. NR 1 TC 1 Z9 1 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 771 EP 771 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68601874 ER PT J AU CHOU, CL KNEPPER, MA AF CHOU, CL KNEPPER, MA TI EXPRESSION OF CA2+-INDEPENDENT PROTEIN-KINASE-C ISOFORMS IN RAT INNER MEDULLARY COLLECTING DUCT SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. NR 1 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 786 EP 786 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68601934 ER PT J AU MADRENAS, J SCHWARTZ, RH GERMAIN, RN AF MADRENAS, J SCHWARTZ, RH GERMAIN, RN TI T-CELL ANERGY IS NOT DETERMINED BY THE PATTERN OF EARLY TCR SIGNALS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. NIAID,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 840 EP 840 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602149 ER PT J AU KUZE, K SUNAMOTO, M KOMATSU, T IEHARA, N TAKEOKA, H YAMADA, Y KITA, T DOI, T AF KUZE, K SUNAMOTO, M KOMATSU, T IEHARA, N TAKEOKA, H YAMADA, Y KITA, T DOI, T TI ACTIVATION OF A DNA-REPLICATION FACTOR-C SUBUNIT CORRELATED WITH BOTH GLOMERULAR PROLIFERATION AND SCLEROSIS IN RENAL ABLATION MODEL SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 KYOTO UNIV,FAC MED,DEPT CLIN BIOREGULATORY SCI,DIV MOLEC MED ADULT & GERIATR DIS,KYOTO 606,JAPAN. KYOTO UNIV,FAC MED,DIV ARTIFICIAL KIDNEYS,KYOTO 606,JAPAN. KYOTO NATL HOSP,DIV CARDIOL,KYOTO 612,JAPAN. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 873 EP 873 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602279 ER PT J AU RAPPAPORT, J RICHARDSON, MW COPELAND, TD KLOTMAN, PE AF RAPPAPORT, J RICHARDSON, MW COPELAND, TD KLOTMAN, PE TI NEPHROPATHY IN HIV TRANSGENIC MICE - POTENTIAL ROLE OF IRON DEPOSITION AND ALPHA-2-MACROGLOBULIN SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MT SINAI MED CTR,DIV NEPHROL,NEW YORK,NY 10029. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 881 EP 881 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602311 ER PT J AU MOZES, M SHRIVASTAV, S FACTOR, V THORGEIRSSON, SS KOPP, JB AF MOZES, M SHRIVASTAV, S FACTOR, V THORGEIRSSON, SS KOPP, JB TI INCREASED INTERSTITIAL MATRIX AND TIMP-1 EXPRESSION IN TGF-BETA-1 TRANSGENIC MOUSE KIDNEY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,KIDNEY DIS SECT,BETHESDA,MD. NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. RI Mozes, Miklos/E-9003-2011 NR 1 TC 0 Z9 0 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 903 EP 903 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602398 ER PT J AU AUSTIN, HA PATEL, AD BALOW, JE AF AUSTIN, HA PATEL, AD BALOW, JE TI IMMUNOLOGICAL EFFECTS OF SHORT COURSES OF PULSE CYCLOPHOSPHAMIDE IN A MURINE MODEL OF SLE SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,KIDNEY DIS SECT,BETHESDA,MD. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 918 EP 918 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602458 ER PT J AU ESPOSITO, C SAKAI, H PATEL, A LIU, ZH YAGAME, M SUZUKI, D STRIKER, GE STRIKER, LJ AF ESPOSITO, C SAKAI, H PATEL, A LIU, ZH YAGAME, M SUZUKI, D STRIKER, GE STRIKER, LJ TI ALPHA-2 TYPE-IV COLLAGEN MESSENGER-RNA IS INCREASED IN GLOMERULI FROM IGA NEPHROPATHY BY COMPETITIVE PCR SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,RENAL CELL BIOL SECT,BETHESDA,MD. TOKAI UNIV,DEPT INTERNAL MED,DIV NEPHROL & METAB,ISEHARA,KANAGAWA,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 921 EP 921 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602472 ER PT J AU LEFKOWITH, JB KIEHL, M GOURLEY, M AF LEFKOWITH, JB KIEHL, M GOURLEY, M TI GLOMERULAR BINDING-ANTIBODIES IN LUPUS NEPHRITIS PATIENTS - CHARACTERIZATION AND CLINICAL-SIGNIFICANCE SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 WASHINGTON UNIV,SCH MED,ST LOUIS,MO. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 925 EP 925 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602486 ER PT J AU ROMANOV, V NOIRI, E GOLIGORSKY, MS AF ROMANOV, V NOIRI, E GOLIGORSKY, MS TI MAPPING OF ARG-GLY-ASP (RGD) BINDING-SITES IN THE ISCHEMIC RAT-KIDNEY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NCI,FREDERICK,MD 21701. SUNY STONY BROOK,STONY BROOK,NY 11794. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 988 EP 988 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602738 ER PT J AU APOSTOL, EL TERRIS, J ECELBARGER, CA ANDREWS, P KNEPPER, MA AF APOSTOL, EL TERRIS, J ECELBARGER, CA ANDREWS, P KNEPPER, MA TI AQUAPORIN WATER CHANNEL EXPRESSION IN PUROMYCIN AMINONUCLEOSIDE (PAN) NEPHROSIS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. GEORGETOWN UNIV,WASHINGTON,DC. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 1009 EP 1009 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602822 ER PT J AU FROKIAER, J MARPLES, D KNEPPER, M NIELSEN, S AF FROKIAER, J MARPLES, D KNEPPER, M NIELSEN, S TI BILATERAL URETERAL OBSTRUCTION DOWN-REGULATES EXPRESSION OF THE VASOPRESSIN-SENSITIVE AQUAPORIN-2 WATER CHANNEL IN RAT-KIDNEY MEDULLA SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 AARHUS UNIV,AARHUS,DENMARK. NHLBI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 1012 EP 1012 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602836 ER PT J AU HE, CJ STRIKER, GE ESPOSITO, C PHILLIPS, C ZALUPS, RK HENDERSON, DA STRIKER, LJ AF HE, CJ STRIKER, GE ESPOSITO, C PHILLIPS, C ZALUPS, RK HENDERSON, DA STRIKER, LJ TI GLOMERULOSCLEROSIS AND EXTRACELLULAR-MATRIX (ECM) TURNOVER - CORRELATION WITH MOUSE STRAIN, RATHER THAN NEPHRON NUMBER, SIZE, OR LABELING INDEX SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,MDB,RCBS,BETHESDA,MD 20892. MERCER UNIV,MACON,GA 31207. OKLAHOMA STATE UNIV,TULSA,OK. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 1015 EP 1015 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602849 ER PT J AU HE, CJ ESPOSITO, C PHILLIPS, C STRIKER, GE STRIKER, LJ AF HE, CJ ESPOSITO, C PHILLIPS, C STRIKER, GE STRIKER, LJ TI GLOMERULOSCLEROSIS - PRESENCE IN DEVELOPMENTAL OLIGONEPHRONIA, ABSENCE IN NEPHRON ABLATION DURING ADULTHOOD, IN THE SAME MOUSE STRAIN SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,MDB,RCBS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 1016 EP 1016 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602850 ER PT J AU NOLAN, PJ KNEPPER, MA PACKER, RK AF NOLAN, PJ KNEPPER, MA PACKER, RK TI ROLE OF ADRENAL-STEROIDS IN ACUTE METABOLIC-ACIDOSIS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD. GEORGE WASHINGTON UNIV,WASHINGTON,DC. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 1025 EP 1025 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602889 ER PT J AU TONSHOFF, B POWELL, DR ZHAO, DL DOMENE, HM BLUM, WF MOORE, LC KASKEL, FJ AF TONSHOFF, B POWELL, DR ZHAO, DL DOMENE, HM BLUM, WF MOORE, LC KASKEL, FJ TI DECREASED HEPATIC INSULIN-LIKE GROWTH-FACTOR (IGF)-I AND INCREASED IGF BINDING-PROTEIN (IGFBP)-1 AND (IGFBP)-2 GENE-EXPRESSION IN EXPERIMENTAL UREMIA SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 SUNY STONY BROOK,DEPT PEDIAT,STONY BROOK,NY. SUNY STONY BROOK,DEPT PHYSIOL,STONY BROOK,NY. BAYLOR COLL MED,HOUSTON,TX. NIDDK,BETHESDA,MD. NR 0 TC 5 Z9 5 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 1032 EP 1032 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602917 ER PT J AU VANGOOR, H DIAMOND, JR DING, G STETLERSTREVENSON, WG AF VANGOOR, H DIAMOND, JR DING, G STETLERSTREVENSON, WG TI METALLOPROTEINASE TYPE-2 (MMP-2) IN EXPERIMENTAL NEPHROTIC SYNDROME-H SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV GRONINGEN HOSP,DEPT PATHOL,GRONINGEN,NETHERLANDS. MILTON S HERSHEY MED CTR,DEPT MED & MOLEC & CELL PHYS,HERSHEY,PA. NCI,PATHOL LAB,BETHESDA,MD 20892. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 1034 EP 1034 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602922 ER PT J AU CLEMENTS, R ZIYADEH, FN ROBISON, G COHEN, MP AF CLEMENTS, R ZIYADEH, FN ROBISON, G COHEN, MP TI DIABETIC RENAL RETINAL SYNDROME IN DB/DB MOUSE SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV PENN,PHILADELPHIA,PA 19104. NEI,BETHESDA,MD. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 1038 EP 1038 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602939 ER PT J AU LIU, ZH STRIKER, LJ PHILLIPS, C CHEN, NY CHEN, WY ESPOSITO, C KOPCHICK, JJ STRIKER, GE AF LIU, ZH STRIKER, LJ PHILLIPS, C CHEN, NY CHEN, WY ESPOSITO, C KOPCHICK, JJ STRIKER, GE TI MICE TRANSGENIC FOR A GROWTH-HORMONE ANTAGONIST ARE PROTECTED FROM DIABETIC GLOMERULOSCLEROSIS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,RCBS,BETHESDA,MD. OHIO UNIV,EBI,DZ,ATHENS,OH 45701. NR 2 TC 1 Z9 1 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 1044 EP 1044 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68602963 ER PT J AU HARMON, SA EMERSON, SU HUANG, YK SUMMERS, DF EHRENFELD, E AF HARMON, SA EMERSON, SU HUANG, YK SUMMERS, DF EHRENFELD, E TI HEPATITIS-A VIRUSES WITH DELETIONS IN THE 2A GENE ARE INFECTIOUS IN CULTURED-CELLS AND MARMOSETS SO JOURNAL OF VIROLOGY LA English DT Article ID RECOMBINANT VACCINIA VIRUS; A VIRUS; BS-C-1 CELLS; CLEAVAGE; POLYPROTEIN; PROTEINASE; RNA; REPLICATION; REGION; PARTICLES AB The 2A gene of hepatitis A virus (HAV) bears no obvious similarity to the corresponding genes of other picornaviruses and has no known function. In a preliminary effort to gain information about the HAV 2A gene product, we constructed several HAV cDNAs containing deletions of 30 or 45 nucleotides in the predicted central portion of the 2A gene. These deletions did not affect the sites of protein processing, although the rates or efficiencies of polyprotein cleavage at the surrounding cleavage junctions appeared slightly reduced. Transfection of FRhK-4 cells with RNA transcripts of the deleted HAV cDNAs generated small foci of infected cells and produced infectious virus that retained the deletion mutations. In contrast, a single amino acid insertion in the 2B coding region was lethal to virus replication despite normal protein processing. Another deletion, which included the predicted 2A/2B junction and extended into the 2B coding sequence, did not support polyprotein processing or generate viable virus. One of the viable internal 2A deletions was introduced into a wild-type HAV cDNA background, and transcripts were tested for infectivity by inoculation directly into the livers of two marmosets. Both animals seroconverted, displayed elevated serum liver enzymes, and excreted infectious virus. Thus, deletion of 10 or 15 amino acid residues from the predicted central portion of the 2A protein was tolerated with only relatively minor effects on the growth of HAV in cultured cells and in marmoset liver. C1 UNIV CALIF IRVINE,DEPT MOLEC BIOL & BIOCHEM,IRVINE,CA 92717. UNIV CALIF IRVINE,DEPT MICROBIOL & MOLEC GENET,IRVINE,CA 92717. UNIV CALIF IRVINE,DEPT MED,IRVINE,CA 92717. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. FU NIAID NIH HHS [AI 12387, AI 26350] NR 35 TC 20 Z9 20 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 SEP PY 1995 VL 69 IS 9 BP 5576 EP 5581 PG 6 WC Virology SC Virology GA RN986 UT WOS:A1995RN98600046 PM 7637003 ER PT J AU TAN, W FELBER, BK ZOLOTUKHIN, AS PAVLAKIS, GN SCHWARTZ, S AF TAN, W FELBER, BK ZOLOTUKHIN, AS PAVLAKIS, GN SCHWARTZ, S TI EFFICIENT EXPRESSION OF THE HUMAN PAPILLOMAVIRUS TYPE-16 L1 PROTEIN IN EPITHELIAL-CELLS BY USING REV AND THE REV-RESPONSIVE ELEMENT OF HUMAN-IMMUNODEFICIENCY-VIRUS OR THE CIS-ACTING TRANSACTIVATION ELEMENT OF SIMIAN RETROVIRUS TYPE-1 SO JOURNAL OF VIROLOGY LA English DT Article ID VIRAL MESSENGER-RNA; GENE-EXPRESSION; TARGET SEQUENCE; C-FOS; FUNCTIONAL-ANALYSIS; SECONDARY STRUCTURE; VIRION EXPRESSION; CODING REGION; DNA-SEQUENCE; HIV-1 AB Production of the human papillomavirus (HPV) late gene products L1 and L2 is limited to terminally differentiated keratinocytes. Here, we demonstrate that mRNA encoding the HPV-16 L1 capsid protein contains cis-acting RNA elements that inhibit expression at the posttranscriptional level. While cytoplasmic L1 mRNA is detectable in transfected HeLa cells, L1 protein is not produced. We have identified at least one major inhibitory element that is located within the L1 open reading frame, whereas another negative element had been reported to lie in the 3'-untranslated region of L1. The presence of these elements may explain the lack of HPV late gene expression in undifferentiated epithelial cells. Efficient production of HPV-16 L1 could be achieved with posttranscriptional regulatory elements of human immunodeficiency virus type 1 or simian retrovirus type 1. L1 protein was expressed in the presence of human immunodeficiency virus type 1 Rev from hybrid mRNAs containing the RNA binding site for Rev (Rev-responsive element). In addition, we have achieved efficient expression of L1 from hybrid mRNAs containing a cis-acting transactivation element from simian retrovirus type 1. Our data show that HPV-16 L1 protein production is regulated posttranscriptionally. This regulated expression may allow virus production in terminally differentiated epithelial cells and is probably a conserved and important mechanism for HPV expression. C1 KAROLINSKA INST,CTR MICROBIOL & TUMORBIOL,S-17177 STOCKHOLM,SWEDEN. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,HUMAN RETROVIRUS PATHOGENESIS 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-46000] NR 77 TC 73 Z9 79 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1995 VL 69 IS 9 BP 5607 EP 5620 PG 14 WC Virology SC Virology GA RN986 UT WOS:A1995RN98600050 PM 7637007 ER PT J AU GROSFELD, H HILL, MG COLLINS, PL AF GROSFELD, H HILL, MG COLLINS, PL TI RNA REPLICATION BY RESPIRATORY SYNCYTIAL VIRUS (RSV) IS DIRECTED BY THE N-PROTEIN, P-PROTEIN, AND L PROTEIN - TRANSCRIPTION ALSO OCCURS UNDER THESE CONDITIONS BUT REQUIRES RSV SUPERINFECTION FOR EFFICIENT SYNTHESIS OF FULL-LENGTH MESSENGER-RNA SO JOURNAL OF VIROLOGY LA English DT Article ID VACCINIA VIRUS; MESSENGER-RNA; GENOMIC RNA; NUCLEOCAPSID PROTEIN; EXPRESSION SYSTEM; SEQUENCE-ANALYSIS; MAMMALIAN-CELLS; INFLUENZA-VIRUS; SENDAI VIRUS; FOREIGN GENE AB Previously, a cDNA was constructed so that transcription by T7 RNA polymerase yielded a similar to 1-kb negative-sense analog of genomic RNA of human respiratory syncytial virus (RSV) containing the gene for chloramphenicol acetyltransferase (CAT) under the control of putative RSV transcription motifs and flanked by the RSV genomic termini. When transfected into RSV-infected cells, this minigenome was ''rescued,'' as evidenced by high levels of CAT expression and the production of transmissible particles which propagated and expressed high levels of CAT expression during serial passage (P. L. collins, M. A. Mink, and D. S. Stec, Proc. Natl. Acad. Sci. USA, 88:9663-9667, 1991). Here, this cDNA, together with a second one designed to yield an exact-copy positive-sense RSV-CAT RNA antigenome, were each modified to contain a self-cleaving hammerhead ribozyme for the generation of a nearly exact 3' end. Each cDNA was transfected into cells infected with a vaccinia virus recombinant expressing T7 RNA polymerase, together with plasmids encoding the RSV N, P, and L proteins, each under the control of a T7 promoter. When the plasmid-supplied template was the mini-antigenome, the minigenome was produced. When the plasmid-supplied template was the minigenome, the products were mini-antigenome, subgenomic polyadenylated mRNA and progeny minigenome. Identification of progeny minigenome made from the plasmid-supplied minigenome template indicates that the full RSV RNA replication cycle occurred. RNA synthesis required all three RSV proteins, N, P, and L, and was ablated completely by the substitution of Asn for Asp at position 989 in the L protein. Thus, the N, P, and L proteins were sufficient for the synthesis of correct minigenome and antigenome, but this was not the case for subgenomic mRNA, indicating that the requirements for RNA replication and transcription are not identical. Complementation with N, P, and L alone yielded an mRNA pattern containing a large fraction of molecules of incomplete, heterogeneous size. In contrast, complementation with RSV (supplying all of the RSV gene products) yielded a single discrete mRNA band. Superinfection with RSV of cells staging N/P/L;based RNA synthesis yielded the single discrete mRNA species. Some additional factor supplied by RSV superinfection appeared to be involved in transcription, the most obvious possibility being one or more additional RSV gene products. C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. NR 44 TC 130 Z9 133 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 SEP PY 1995 VL 69 IS 9 BP 5677 EP 5686 PG 10 WC Virology SC Virology GA RN986 UT WOS:A1995RN98600057 PM 7637014 ER PT J AU GOREN, I SEMMES, OJ JEANG, KT MOELLING, K AF GOREN, I SEMMES, OJ JEANG, KT MOELLING, K TI THE AMINO-TERMINUS OF TAX IS REQUIRED FOR INTERACTION WITH THE CYCLIC-AMP RESPONSE ELEMENT-BINDING PROTEIN SO JOURNAL OF VIROLOGY LA English DT Note ID T-CELL LEUKEMIA; VIRUS TYPE-I; HTLV-I; TRANSCRIPTIONAL ACTIVATOR; 21-BASE-PAIR REPEATS; RNA-POLYMERASE; TRANSACTIVATOR; ENHANCER; GENES; EXPRESSION AB Tax of human T-cell leukemia virus type 1 was analyzed for interaction with the cyclic AMP response element binding protein (CREB) in vitro with and without Tax response element DNA. Mutations in the carboxy terminus of Tax (L296G and L320G) did not affect binding to CREB and led to supershifts. In contrast, mutants with changes in the amino-terminal cysteine-rich region lost the ability to bind to CREB. The S10A mutant protein bound moderately. Thus, the amino terminus of Tax is essential for Tax-CREB interaction. C1 UNIV ZURICH,INST MED VIROL,CH-8028 ZURICH,SWITZERLAND. MAX PLANCK INST MOLEC GENET,D-14195 BERLIN,GERMANY. NIAID,MOLEC BIOL LAB,MOLEC VIROL SECT,BETHESDA,MD 20892. RI Jeang, Kuan-Teh/A-2424-2008 NR 43 TC 65 Z9 65 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 SEP PY 1995 VL 69 IS 9 BP 5806 EP 5811 PG 6 WC Virology SC Virology GA RN986 UT WOS:A1995RN98600072 PM 7637025 ER PT J AU ENGELMAN, A CRAIGIE, R AF ENGELMAN, A CRAIGIE, R TI EFFICIENT MAGNESIUM-DEPENDENT HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INTEGRASE ACTIVITY SO JOURNAL OF VIROLOGY LA English DT Note ID ESCHERICHIA-COLI; VIRAL-DNA; PROTEIN; INVITRO; IDENTIFICATION; ENDONUCLEASE; SPECIFICITY; POLYMERASE; HIV-1 AB The integrase protein from human immunodeficiency virus type 1 (HIV-1) has generally been reported to require Mn2+ for efficient in vitro activity. We have reexamined the divalent metal ion requirements of HIV-1 integrase and find that the protein is capable of promoting efficient 3' processing and DNA strand transfer with either Mn2+ or Mg2+. The metal ion preference depended upon the reaction conditions. HIV-1 integrase displayed significantly less nonspecific nuclease activity in reaction mixtures containing Mg2+ than it did under the previously described reaction conditions with mixtures containing Mn2+. C1 NIDDK,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 27 TC 83 Z9 87 U1 1 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 SEP PY 1995 VL 69 IS 9 BP 5908 EP 5911 PG 4 WC Virology SC Virology GA RN986 UT WOS:A1995RN98600092 PM 7637039 ER PT J AU CHERNOMORDIK, L LEIKINA, E CHO, MS ZIMMERBERG, J AF CHERNOMORDIK, L LEIKINA, E CHO, MS ZIMMERBERG, J TI CONTROL OF BACULOVIRUS GP64-INDUCED SYNCYTIUM FORMATION BY MEMBRANE LIPID-COMPOSITION (VOL 69, PG 3053, 1995) SO JOURNAL OF VIROLOGY LA English DT Correction, Addition RP CHERNOMORDIK, L (reprint author), NICHHD,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892, 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 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1995 VL 69 IS 9 BP 5928 EP 5928 PG 1 WC Virology SC Virology GA RN986 UT WOS:A1995RN98600097 ER PT J AU LANE, MA BAER, DJ TILMONT, EM RUMPLER, WV INGRAM, DK ROTH, GS CUTLER, RG AF LANE, MA BAER, DJ TILMONT, EM RUMPLER, WV INGRAM, DK ROTH, GS CUTLER, RG TI ENERGY-BALANCE IN RHESUS-MONKEYS (MACACA-MULATTA) SUBJECTED TO LONG-TERM DIETARY RESTRICTION SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID DOUBLY LABELED WATER; AGE-RELATED DISEASE; FOOD RESTRICTION; METABOLIC-RATE; AGING PROCESS; FISCHER RATS; EXPENDITURE; LONGEVITY AB Male rhesus monkeys of various age groups representative of the species life span were fed ad libitum amounts (controls) or 30% less food than control monkeys of comparable age and body weight. Despite significantly lowered energy intake and body weight, the amount of energy lost in the feces, and fecal energy density (concentration) were trot altered in diet-restricted (DR) monkeys, compared to age- and weight-matched controls. Absolute energy expenditure (EE; 24-hr) was consistently lower in DR monkeys, but this trend was not statistically significant. Expressed as a function of metabolic mass (body weight, metabolic body size, lean mass), 24-hr EE was not different in monkeys subjected to long-term DR, compared to controls. Calculations of net energy (intake - loss), as an index of energy balance, revealed that Energy expenditure generally exceeded energy intake ill all juvenile and adult group monkeys. However, this discrepancy was not statistically different from zero, suggesting that most animals were in energy balance. Also, there was no difference between control and DR animals with respect to energy balance. Diet restriction induced significant reductions in the absolute amount of lean body mass; however, percent (of total weight) lean and fat mass did not differ from controls. C1 USDA ARS,BELTSVILLE AGR RES CTR,HUMAN NUTR RES CTR,PROT & ENERGY NUTR LAB,BELTSVILLE,MD 20705. NATL INST HLTH ANIM CTR,PRIMATE UNIT,POOLESVILLE,MD. RP LANE, MA (reprint author), NIA,HOPKINS BAYVIEW MED CTR,GERONTOL RES CTR,MOLEC PHYSIOL & GENET SECT,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 31 TC 34 Z9 34 U1 0 U2 3 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD SEP PY 1995 VL 50 IS 5 BP B295 EP B302 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA RY605 UT WOS:A1995RY60500008 PM 7671021 ER PT J AU BLAZER, DG HAYS, JC FOLEY, DJ AF BLAZER, DG HAYS, JC FOLEY, DJ TI SLEEP COMPLAINTS IN OLDER ADULTS - A RACIAL COMPARISON SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID SPOUSAL BEREAVEMENT; APNEA SYNDROME; PREVALENCE; MORTALITY; EPIDEMIOLOGY; DISORDERS; COMMUNITY; INSOMNIA AB Background. Sleep complaints have been reported in epidemiologic studies to be more frequent in late life, among females, among the physically impaired, and among persons experiencing psychiatric disorders. To date, however, no studies have reported a racial difference in sleep complaints among older persons in the United States. Method. The Duke EPESE (Established Populations for Epidemiologic Studies of the Elderly) assessed 3,976 community-dwelling elders age 65+ for sleep complaints and relevant control variables. Results. In bivariate analyses, sleep complaints were associated with female gender. White race, older age, cognitive impairment, lower education, presence of chronic health conditions, poor self-rated health, and higher scores on a self-rated depression scale (the CES-D). In logistic regression analysis, the association of White race and more sleep complaints persisted (p <.001) when the above variables were simultaneously controlled. Conclusions. Fewer reported sleep complaints in community-dwelling Black elders compared to White elders remains unexplained, though it may be secondary to a higher threshold for Black elders reporting complaints. C1 DUKE UNIV,CTR STUDY AGING & HUMAN DEV,DURHAM,NC. NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. RP BLAZER, DG (reprint author), DUKE UNIV,MED CTR,DEPT PSYCHIAT,BOX 3005,DURHAM,NC 27710, USA. FU NIA NIH HHS [N01-AG-4-2110] NR 26 TC 54 Z9 54 U1 0 U2 3 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD SEP PY 1995 VL 50 IS 5 BP M280 EP M284 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA RY605 UT WOS:A1995RY60500019 PM 7671031 ER PT J AU LIU, ZH STRIKER, LJ PHILLIPS, C CHEN, NY CHEN, WY KOPCHICK, JJ STRIKER, GE AF LIU, ZH STRIKER, LJ PHILLIPS, C CHEN, NY CHEN, WY KOPCHICK, JJ STRIKER, GE TI GROWTH-HORMONE EXPRESSION IS REQUIRED FOR THE DEVELOPMENT OF DIABETIC GLOMERULOSCLEOROSIS IN MICE SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT 2nd Hyonam-Kidney-Laboratory International Symposium on Pathogenesis of Diabetic Nephropathy - Experimental Approaches CY JAN 21, 1995 CL SEOUL, SOUTH KOREA SP Hyonam Kidney Lab ID TRANSGENIC MICE; MELLITUS C1 NIDDKD,METAB DIS BRANCH,RENAL CELL BIOL SECT,BETHESDA,MD 20892. OHIO UNIV,DEPT BIOL SCI,PROGRAM MOLEC & CELLULAR BIOL,ATHENS,OH 45701. OHIO UNIV,EDISON BIOTECHNOL INST,ATHENS,OH 45701. NR 11 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 1995 VL 48 SU 51 BP S37 EP S38 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA RR159 UT WOS:A1995RR15900008 ER PT J AU Choi, YH Park, KY Lee, SM Yoo, MA Lee, WH AF Choi, YH Park, KY Lee, SM Yoo, MA Lee, WH TI Inhibitory effect of the fresh juice of kale on the genotoxicity of aflatoxin B-1 SO KOREAN JOURNAL OF GENETICS LA English DT Article DE kale; aflatoxin B-1; salmonella; drosophila ID DROSOPHILA-MELANOGASTER; ANTIMUTAGENIC ACTIVITY; MUTAGENICITY TEST; X-RAYS; CHLOROPHYLLIN; VEGETABLES; ASSAY; CARCINOGENS; MUTATION; FRUITS AB The inhibitory effect of the fresh juice of kale on the genotoxicity induced by aflatoxin B1 (AFB1) in Salmonella and Drosophila was investigated. The kale juice had strong inhibitory activity for His(-) to His(+) reverse-mutations induced by AFB1 acting on S. typhimurium TA100. A similar inhibitory effect was detected in somatic cell mutation assaying system of D. melanogaster. Using the wing hairs spot test, we found that the formation of mutant hairs in adult flies as a result of feeding with AFB1 in their larval stages was efficiently inhibited by coadministration of the fresh juice of kale, which revealed that it can inhibit gene mutation, deletion and mitotic chromosomal recombination. These results seem to suggest that kale juice may exert its inhibitory effect to mutagenic and/or carcinogenic properties of DNA damaging agents. C1 NCI,MED BRANCH,BETHESDA,MD 20892. PUSAN NATL UNIV,DEPT FOOD SCI & NUTR,PUSAN 609735,SOUTH KOREA. PUSAN NATL UNIV,DEPT MOLEC BIOL,PUSAN 609735,SOUTH KOREA. PUSAN NATL UNIV,DEPT BIOL,PUSAN 609735,SOUTH KOREA. NR 37 TC 1 Z9 1 U1 0 U2 0 PU GENETICS SOC KOREA PI SEOUL PA SEOUL NATL UNIV, DEPT BIOLOGY, COLL EDUCATION, SINLIMDONG SAN 56-1, KWANAKGU, SEOUL 151-742, SOUTH KOREA SN 0254-5934 J9 KOREAN J GENETIC JI Korean J. Genet. PD SEP PY 1995 VL 17 IS 3 BP 183 EP 190 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA TR456 UT WOS:A1995TR45600004 ER PT J AU TAKAHASHI, K VIVIANO, CJ ELWELL, MR BAKEWELL, WE KUWAHARA, M NAKASHIMA, N BLACKWELL, BN MARONPOT, RR AF TAKAHASHI, K VIVIANO, CJ ELWELL, MR BAKEWELL, WE KUWAHARA, M NAKASHIMA, N BLACKWELL, BN MARONPOT, RR TI BILE DUCT-SPECIFIC LECTINS, DOLICHOS-BIFLORUS AGGLUTININ AND PEANUT AGGLUTININ, AS PROBES IN MOUSE HEPATOCARCINOGENESIS SO LABORATORY INVESTIGATION LA English DT Article DE MOUSE LIVER TUMORS; HISTOCHEMISTRY; IMMUNOHISTOCHEMISTRY; CYTOKERATIN; HEPATOCHOLANGIOCARCINOMA ID PRIMARY BILIARY-CIRRHOSIS; MONOCLONAL-ANTIBODIES; CYTO-CHEMISTRY; BINDING-SITES; LIVER-CELLS; GLYCOSYLATION; GLYCOPROTEIN; EXPRESSION; IMMUNOPEROXIDASE; ANTIGENS AB BACKGROUND: It is well established that alterations in the expression of cell surface glycoproteins occur during the course of tumorigenesis and can be detected immunohistochemically. However, no consistent markers of malignancy in mouse hepatocellular tumors have yet been identified. EXPERIMENTAL DESIGN: Lectin histochemistry, using three bile duct-specific lectins, Dolichos biflorus agglutinin (DBA), peanut agglutinin (PNA) and soybean agglutinin (SBA), and anti-epidermal keratin immunohistochemistry, was conducted on formalin-fixed, paraffin-embedded tissues of a spectrum of benign and malignant hepatocellular proliferative lesions of mice, including hepatocholangiocarcinomas. DBA- and PNA-binding glycoproteins in normal livers and in bile and Liver tumors of mice were verified by SDS-PAGE and Western blot analysis. RESULTS: Normal bile duct cells stained strongly with DBA but minimally to moderately with PNA and SBA. DBA-positive tumor cells were present in 96% of hepatocholangiocarcinomas, 89% of hepatocellular carcinomas, and 35% of hepatocellular adenomas. In comparison, 43% of hepatocholangiocarcinomas, 37% of hepatocellular carcinomas, and 24% of hepatocellular adenomas exhibited PNA staining. SBA did not specifically stain tumor cells. Normal hepatocytes and those in altered foci were consistently negative for these three lectins. Keratin-positive staining was found only in normal bile ductular cells and ductal elements in 70% of hepatocholangiocarcinomas. Electrophoresis and Western blot analysis demonstrated that, in normal livers, DBA and PNA bound to the 13- to 16-kDa and 27- to 30-kDa glycoproteins believed to be of bile duct cell origin and commonly present in hepatocellular adenomas, hepatocellular carcinomas, and hepatocholangiocarcinomas, with strongest expression in the last. In addition hepatocholangiocarcinomas had the same high molecular mass glycoprotein (>200 kDa) labeled with DBA as detected in bile. CONCLUSIONS: Our results suggest that some malignant hepatocytes, especially in mouse hepatocholangiocarcinomas, have the potential of biliary differentiation. DBA is a sensitive marker for malignant hepatocytes in mice. C1 NIEHS,RES TRIANGLE PK,NC 27709. INST ENVIRONM TOXICOL,TOKYO,JAPAN. NATL CTR TOXICOL RES,PATHOL ASSOCIATES INC,JEFFERSON,AR 72079. NR 44 TC 6 Z9 6 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 SEP PY 1995 VL 73 IS 3 BP 424 EP 432 PG 9 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA RV087 UT WOS:A1995RV08700014 PM 7564276 ER PT J AU LIECHTY, MC HALL, BK SCALZI, JM DAVIS, LM CASPARY, WJ HOZIER, JC AF LIECHTY, MC HALL, BK SCALZI, JM DAVIS, LM CASPARY, WJ HOZIER, JC TI MOUSE CHROMOSOME-SPECIFIC PAINTING PROBES GENERATED FROM MICRODISSECTED CHROMOSOMES SO MAMMALIAN GENOME LA English DT Article ID DNA PROBES; ABERRATIONS; RADIATION; CELLS AB Using degenerate primer amplification of chromosomes microdissected from banded cytogenetic preparations, we constructed both whole chromosome painting probes for mouse Chromosomes (Chrs) 1, 2, 3, and 11 and a centromere probe that strongly paints most mouse centromeres. We also amplified a Robertsonian translocation chromosome microdissected from unstained preparations to construct a painting probe for Chrs 9 and 19. The chromosomes probes uniformly painted the respective chromosomes of origin. We demonstrated the utility of the Chr 11 probe in aberration analysis by staining mutants that we had previously identified as containing a Chr 11 translocation, and in some mutant cell lines we observed chromosome rearrangements not previously detected in stained cytogenetic preparations. The technology of microdissection and amplification applies to all mouse chromosomes or to specific subchromosomal legions and will be useful in mouse genetics, in aberration analysis, and for chromosome identification. C1 NIEHS,ENVIRONM CARCINOGENESIS & MUTAGENESIS LAB,RES TRIANGLE PK,NC 27709. RP LIECHTY, MC (reprint author), APPL GENET LABS INC,1335 GATEWAY DR,SUITE 2001,MELBOURNE,FL 32901, USA. FU NIEHS NIH HHS [N43-ES-21002]; NIGMS NIH HHS [IR43GM50114-01] NR 19 TC 9 Z9 10 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 SEP PY 1995 VL 6 IS 9 BP 592 EP 594 DI 10.1007/BF00352363 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA RU971 UT WOS:A1995RU97100005 PM 8535064 ER PT J AU CLERICI, M VILLA, ML TRABATTONI, D SHEARER, GM AF CLERICI, M VILLA, ML TRABATTONI, D SHEARER, GM TI THE BREAKDOWN OF THE CYTOKINE NETWORK SUBSEQUENT TO HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION SO MEDIATORS OF INFLAMMATION LA English DT Review DE BREAKDOWN; CYTOKINE NETWORK; HIV ID T-HELPER CELL; HIV-INFECTION; IN-VITRO; AIDS; PROGRESSION; DEPLETION; DYSFUNCTION; TYPE-1; RESPONSES; PHENOTYPE AB The acquired immunodeficiency syndrome (AIDS) is a clinically multifaceted disease induced by infection with the human immunodeficiency virus (HIV). HIV infection results in a complex pattern of immunologic alterations that leads to the development of AIDS in the majority of HIV seropositive (HIV+) individuals. The reduction in CD4 T lymphocyte counts is the hallmark of HIV infection; nevertheless, long before the reduction in CD4 counts reaches critical levels, a series of profound and complex defects that impair the function of CD4 T lymphocytes can be detected. Thus, HIV infection is characterized by quantitative and qualitative defects affecting CD4 T lymphocytes. It was suggested recently that programmed cell death (PCD) is an important mechanism leading to CD4 depletion in HIV infection, and that susceptibility of peripheral lymphocytes to PCD is differentially regulated by diverse cytokines. Thus, type 1 cytokines would protect CD4 lymphocytes against PCD, whereas type 2 cytokines would not protect against, and could augment, PCD. We suggest that the qualitative alterations of the immune response provoke the CD4 depletion characteristic of HIV disease via type 2 cytokine-mediated augmentation of PCD, and are therefore ultimately responsible for the progression of HIV infection. Finally, we summarize recent data showing that three correlates of disease progression: emergence of HIV strains with syncitium-inducing ability (SI), type 1-to-type 2 cytokine shift, and CD4 depletion, are significantly associated, suggesting a complex interconnected virologic-immunologic pathogenesis of HIV infection. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RP CLERICI, M (reprint author), UNIV MILAN,CATTEDRA IMMUNOL,MILAN,ITALY. RI Trabattoni, Daria/G-7424-2012 NR 68 TC 0 Z9 0 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0962-9351 J9 MEDIAT INFLAMM JI Mediat. Inflamm. PD SEP PY 1995 VL 4 IS 5 BP 315 EP 321 DI 10.1155/S0962935195000512 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA TC002 UT WOS:A1995TC00200001 PM 18475658 ER PT J AU KROOG, GS JENSEN, RT BATTEY, JF AF KROOG, GS JENSEN, RT BATTEY, JF TI MAMMALIAN BOMBESIN RECEPTORS SO MEDICINAL RESEARCH REVIEWS LA English DT Review ID GASTRIN-RELEASING PEPTIDE; SWISS 3T3 CELLS; BETA-ADRENERGIC-RECEPTOR; PROTEIN-KINASE-C; STIMULATE TYROSINE PHOSPHORYLATION; PANCREATIC ACINAR-CELLS; LUNG-CARCINOMA CELLS; HIGH-AFFINITY RECEPTORS; NEUROMEDIN-B RECEPTOR; GUINEA-PIG PANCREAS C1 NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892. NIDOCD,DIV INTRAMURAL RES,NEUROCHEM LAB,BETHESDA,MD. NR 142 TC 119 Z9 125 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0198-6325 J9 MED RES REV JI Med. Res. Rev. PD SEP PY 1995 VL 15 IS 5 BP 389 EP 417 DI 10.1002/med.2610150502 PG 29 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RR682 UT WOS:A1995RR68200001 PM 8531502 ER PT J AU CARROLL, FI SCHEFFEL, U DANNALS, RF BOJA, JW KUHAR, MJ AF CARROLL, FI SCHEFFEL, U DANNALS, RF BOJA, JW KUHAR, MJ TI DEVELOPMENT OF IMAGING AGENTS FOR THE DOPAMINE TRANSPORTER SO MEDICINAL RESEARCH REVIEWS LA English DT Review ID POSITRON EMISSION TOMOGRAPHY; COCAINE RECOGNITION SITES; F-18 GBR 13119; MONOAMINE REUPTAKE SITES; I-123 BETA-CIT; PARKINSONS-DISEASE; BINDING-SITES; RAT-BRAIN; UPTAKE INHIBITOR; PHARMACOLOGICAL CHARACTERIZATION C1 JOHNS HOPKINS MED INST,DIV NUCL MED & RADIAT HLTH SCI,BALTIMORE,MD 21205. NIDA,ADDICT RES CTR,NEUROSCI BRANCH,BALTIMORE,MD 21224. RP CARROLL, FI (reprint author), RES TRIANGLE INST,POB 12194,RES TRIANGLE PK,NC 27709, USA. NR 145 TC 34 Z9 34 U1 1 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0198-6325 J9 MED RES REV JI Med. Res. Rev. PD SEP PY 1995 VL 15 IS 5 BP 419 EP 444 PG 26 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RR682 UT WOS:A1995RR68200002 PM 8531503 ER PT J AU RAVUSSIN, E AF RAVUSSIN, E TI METABOLIC DIFFERENCES AND THE DEVELOPMENT OF OBESITY SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID PIMA-INDIANS; WEIGHT-GAIN; ENERGY-EXPENDITURE; INSULIN RESISTANCE; OXIDATION; RATIO; FAT AB Studies, such as those on Pima Indians, have shown that metabolic factors are involved in the development of obesity and that being overweight is not simply a result of ''sloth and gluttony,'' However, the environment also affects the development of obesity. Among individuals in a given environment, the variability in body size is influenced by genetically determined responses to that environment, People with a low metabolic rate (adjusted for body size and composition) are prone to weight gain, whereas those with a high level of spontaneous physical activity are less likely to become obese. Similarly, individuals with a high 24-hour respiratory quotient (RO) are more likely to gain weight than those with a low RQ. Insulin sensitivity (not insulin resistance) is another metabolic predictor of obesity, Genetic linkage studies suggest a number of genes are linked to the development of obesity. By sibling-pair linkage analysis, tumor necrosis factor-alpha (TNF-alpha) was found to be linked to the percentage of body fat, and other studies have shown that fat cell production of TNF-alpha is greater in obese individuals. Copyright (C) 1995 by W.B. Saunders Company RP RAVUSSIN, E (reprint author), NIDDK,CLIN DIABET & NUTR SECT,PHOENIX,AZ 85016, USA. NR 29 TC 42 Z9 42 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD SEP PY 1995 VL 44 IS 9 SU 3 BP 12 EP 14 DI 10.1016/0026-0495(95)90312-7 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RW679 UT WOS:A1995RW67900004 PM 7674909 ER PT J AU HAJRA, A LIU, PP SPECK, NA COLLINS, FS AF HAJRA, A LIU, PP SPECK, NA COLLINS, FS TI OVEREXPRESSION OF CORE-BINDING FACTOR-ALPHA (CBF-ALPHA) REVERSES CELLULAR-TRANSFORMATION BY THE CBF-BETA-SMOOTH MUSCLE MYOSIN HEAVY-CHAIN CHIMERIC ONCOPROTEIN SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ACUTE MYELOMONOCYTIC LEUKEMIA; DROSOPHILA SEGMENTATION GENE; FUSION TRANSCRIPT; VIRUS ENHANCER; AML1 GENE; POINT MUTATIONS; RECEPTOR-DELTA; NUCLEAR FACTOR; DNA-BINDING AB A fusion between the transcription factor core-binding factor beta (CBF beta; also known as PEBP2 beta) and the tail region of smooth muscle myosin heavy chain (SMMHC) is generated by an inversion of chromosome 16 [inv(16) (p13q22)] associated with the M4Eo subtype of acute myeloid leukemia. We have previously shown that this CBF beta-SMMHC chimeric protein can transform NIH 3T3 cells and that this process requires regions of the chimeric protein necessary for association with the CBF alpha subunit. In this study, we show that NIH 3T3 cells overexpressing murine Cbf alpha 2 (also known as Aml1) cannot be transformed by CBF beta-SMMHC and that overexpression of Cbf alpha 2 in cells previously transformed by CBF beta-SMMHC reverts the cells to a less transformed phenotype. Cbf alpha 2 overexpression does not cause any gross morphological changes to NIH 3T3 cells but does result in increased CBF activity, as indicated by electrophoretic mobility shift assays and transactivation of reporter constructs. Cells transformed by CBF beta-SMMHC lack normal CBF-DNA complexes and have decreased levels of transactivation. Reversion of CBF beta-SMMHC transformation by Cbf alpha 2 is associated with a restoration of normal CBF-DNA complexes and transactivation activity. A Cbf alpha 2 mutant lacking transactivation properties does not transform cells when overexpressed, nor does it protect cells from CBF beta-SMMHC transformation. These results suggest that CBF beta-SMMHC interferes with the normal function of CBF and that this interference is necessary but not sufficient for cellular transformation. C1 NATL CTR HUMAN GENOME RES,GENE TRANSFER LAB,BETHESDA,MD 20892. UNIV MICHIGAN,SCH MED,DEPT HUMAN GENET,ANN ARBOR,MI 48109. DARTMOUTH COLL,SCH MED,DEPT BIOCHEM,HANOVER,NH 03755. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X FU NCI NIH HHS [CA58343-01] NR 64 TC 14 Z9 14 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 SEP PY 1995 VL 15 IS 9 BP 4980 EP 4989 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RQ134 UT WOS:A1995RQ13400037 PM 7651416 ER PT J AU ALEXANDROVA, N NIKLINSKI, J BLISKOVSKY, V OTTERSON, GA BLAKE, M KAYE, FJ ZAJAC-KAYE, M AF ALEXANDROVA, N NIKLINSKI, J BLISKOVSKY, V OTTERSON, GA BLAKE, M KAYE, FJ ZAJAC-KAYE, M TI THE N-TERMINAL DOMAIN OF C-MYC ASSOCIATES WITH ALPHA-TUBULIN AND MICROTUBULES IN-VIVO AND IN-VITRO SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INTRACELLULAR-LOCALIZATION; PROTEINS; NUCLEAR; PRODUCT; TRANSFORMATION; TRANSLOCATION; LYMPHOMA; CELLS; GENE; MAX AB The polymerization of alpha- and beta-tubulin into microtubules results in a complex network of microfibrils that have important structural and functional roles in all eukaryotic cells, In addition, microtubules fan interact with a diverse family of polypeptides which are believed to directly promote the assembly of microtubules and to modulate their functional activity, We have demonstrated that the c-Myc oncoprotein interacts in vivo and in vitro with alpha-tubulin and with polymerized microtubules and have defined the binding site to the N-terminal region within the transactivation domain of c-Myc. In addition, we have shown that c-Myc colocalizes with microtubules and remains tightly bound to the microtubule network after detergent extraction of intact cells, These findings suggest a potential role for Myc-tubulin interaction in vivo. C1 NCI, BIOL CHEM LAB, BETHESDA, MD 20892 USA. NCI, NAVY ONCOL BRANCH, BETHESDA, MD 20892 USA. RI kaye, frederic/E-2437-2011 NR 36 TC 72 Z9 72 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 SEP PY 1995 VL 15 IS 9 BP 5188 EP 5195 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RQ134 UT WOS:A1995RQ13400058 PM 7651436 ER PT J AU DENT, P REARDON, DB MORRISON, DK STURGILL, TW AF DENT, P REARDON, DB MORRISON, DK STURGILL, TW TI REGULATION OF RAF-1 AND RAF-1 MUTANTS BY RAS-DEPENDENT AND RAS-INDEPENDENT MECHANISMS IN-VITRO (VOL 15, PG 4125, 1995) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Correction, Addition C1 UNIV VIRGINIA,MARKEY CTR CELL SIGNALING,DEPT MED,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,DEPT PHARMACOL,CHARLOTTESVILLE,VA 22908. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RP DENT, P (reprint author), HOWARD HUGHES MED INST,CHARLOTTESVILLE,VA 22908, USA. NR 1 TC 2 Z9 2 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 SEP PY 1995 VL 15 IS 9 BP 5203 EP 5203 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RQ134 UT WOS:A1995RQ13400060 ER PT J AU GONZALEZ, P RAO, PV NUNEZ, SB ZIGLER, JS AF GONZALEZ, P RAO, PV NUNEZ, SB ZIGLER, JS TI EVIDENCE FOR INDEPENDENT RECRUITMENT OF ZETA-CRYSTALLIN/QUINONE REDUCTASE (CRYZ) AS A CRYSTALLIN IN CAMELIDS AND HYSTRICOMORPH RODENTS SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE RECRUITMENT OF CRYSTALLINS; PROMOTER FUNCTION; PROMOTER EVOLUTION; LLAMA; GUINEA PIG; ENZYME CRYSTALLIN; OCULAR LENS ID GUINEA-PIG LENS; ENZYME-CRYSTALLINS; LACTATE-DEHYDROGENASE; QUINONE REDUCTASE; EPITHELIAL-CELLS; EYE LENS; GENE; PROTEIN; EXPRESSION; EVOLUTION AB Zeta-crystallin/quinone reductase (CRYZ) is an NADPH oxidoreductase expressed at very high levels in the lenses of two groups of mammals: camelids and some hystricomorph rodents. It is also expressed at very low levels in all other species tested. Comparative analysis of the mechanisms mediating the high expression of this enzyme! crystallin in the lens of the Ilama (Lama guanacoe) and the guinea pig (Cavia porcellus) provided evidence for independent recruitment of this enzyme as a lens crystallin in both species and allowed us to elucidate for the first time the mechanism of lens recruitment of an enzyme-crystallin. The data presented here show that in both species such recruitment most likely occurred through the generation of new lens promoters from nonfunctional intron sequences by the accumulation of point mutations and/or small deletions and insertions. These results further support the idea that recruitment of CRYZ resulted from an adaptive process in which the high expression of CRYZ in the lens provides some selective advantage rather than from a purely neutral evolutionary process. C1 NEI,MECHANISMS OCULAR DIS LAB,BETHESDA,MD 20892. NICHHD,BETHESDA,MD 20892. NR 35 TC 28 Z9 29 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD SEP PY 1995 VL 12 IS 5 BP 773 EP 781 PG 9 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA RQ664 UT WOS:A1995RQ66400006 PM 7476124 ER PT J AU CHEN, H ZHANG, L RUBINOW, DR CHUANG, DM AF CHEN, H ZHANG, L RUBINOW, DR CHUANG, DM TI CHRONIC BUSPIRONE TREATMENT DIFFERENTIALLY REGULATES 5-HT1A AND 5-HT2A RECEPTOR MESSENGER-RNA AND BINDING-SITES IN VARIOUS REGIONS OF THE RAT HIPPOCAMPUS SO MOLECULAR BRAIN RESEARCH LA English DT Note DE 5-HT1A RECEPTOR; 5-HT2A RECEPTOR; IN SITU HYBRIDIZATION; RECEPTOR AUTORADIOGRAPHY; RAT HIPPOCAMPUS; RECEPTOR UP-AND-DOWN-REGULATION ID CENTRAL-NERVOUS-SYSTEM; MESSENGER-RNA; BRAIN; 5-HYDROXYTRYPTAMINE; SUBTYPES; CELLS AB Groups of rats were treated with buspirone (1 mg/kg/day) for 21 days using osmotic minipumps implanted subcutaneously. After buspirone treatment, the 5-HT1A receptor mRNA levels were significantly decreased in the CA1 and CA2 of the hippocampus, but were markedly increased in the dentate gyrus (DG), CA3 and CA4. The level of the 5-HT1A receptor binding sites was not significantly changed in these subhippocampal areas. Buspirone treatment markedly increased 5-HT2A receptor mRNA levels in the DG, CA2, CA3 and CA4. This was accompanied by a significant increase in the level of 5-HT2A receptor binding sites in all subhippocampal regions. These results demonstrate that chronic buspirone treatment differentially regulates 5-HT1A and 5-HT2A receptor mRNA as well as their expressed binding sites in various regions of the hippocampus. C1 NIMH,BIOL PSYCHIAT BRANCH,MOLEC NEUROBIOL SECT,BETHESDA,MD 20892. NIMH,BIOL PSYCHIAT BRANCH,BEHAV ENDOCRINOL SECT,BETHESDA,MD 20892. NR 26 TC 19 Z9 19 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 SEP PY 1995 VL 32 IS 2 BP 348 EP 353 DI 10.1016/0169-328X(95)00098-D PG 6 WC Neurosciences SC Neurosciences & Neurology GA RR930 UT WOS:A1995RR93000020 ER PT J AU OLDEN, K KLEIN, JL AF OLDEN, K KLEIN, JL TI ENVIRONMENTAL-HEALTH SCIENCE RESEARCH AND HUMAN RISK ASSESSMENT SO MOLECULAR CARCINOGENESIS LA English DT Article; Proceedings Paper CT 8th International Conference on Carcinogenesis and Risk Assessment: Genetics and Susceptibility - Impact on Risk Assessment CY NOV 30-DEC 03, 1994 CL AUSTIN, TX DE GENETICS; ENVIRONMENT RISK ASSESSMENT; SUSCEPTIBILITY ID RECEPTORS AB Environmental health science research, with its focus on fundamental science and disease prevention, is important for the development of rational and cost-effective public health and regulatory policies related to environmental protection. Environmentally related diseases are preventable, yet they impose a major burden on society in terms of human suffering and costs related to health care. Similarly, the expenditure of hundreds of billions of dollars for regulatory compliance is a major economic concern. There is considerable debate regarding current regulatory risk assessment practices for environmental agents. Implicit in all risk assessment schemes is the need to extrapolate from high-exposure studies to low-exposure situations and from known risks in rodents to probable risks in people. Both extrapolations are fraught with uncertainties. These uncertainties are accommodated in risk-assessment schemes by the incorporation of arbitrary ''safety factors'' and other default approaches. Since these factors are not derived experimentally, they may overestimate or under estimate actual risks. Risk-assessment methodology, its relevance to the human condition, and its use in protecting human health will greatly improve when our expanding knowledge of the basic biology of environmental effects is incorporated into toxicological testing and risk-assessment schemes. Moreover, exciting opportunities now exist to advance our understanding of the environmental and genetic bases of many common diseases and to design effective prevention and intervention strategies to combat their development. This report discusses some of the current opportunities and challenges. (C) 1995 Wiley-Liss, Inc. C1 NIH,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC. RP OLDEN, K (reprint author), NIEHS,DIV INTRAMURAL RES,ENVIRONM CARCINOGENESIS PROGRAM,MOLEC CARCINOGENESIS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 25 TC 4 Z9 4 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD SEP PY 1995 VL 14 IS 1 BP 2 EP 9 DI 10.1002/mc.2940140103 PG 8 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA RW551 UT WOS:A1995RW55100002 PM 7546220 ER PT J AU ROTHMAN, N SHIELDS, PG POIRIER, MC HARRINGTON, AM FORD, DP STRICKLAND, PT AF ROTHMAN, N SHIELDS, PG POIRIER, MC HARRINGTON, AM FORD, DP STRICKLAND, PT TI THE IMPACT OF GLUTATHIONE-S-TRANSFERASE M1 AND CYTOCHROME-P450 1A1 GENOTYPES ON WHITE-BLOOD-CELL POLYCYCLIC AROMATIC HYDROCARBON-DNA ADDUCT LEVELS IN HUMANS SO MOLECULAR CARCINOGENESIS LA English DT Article; Proceedings Paper CT 8th International Conference on Carcinogenesis and Risk Assessment: Genetics and Susceptibility - Impact on Risk Assessment CY NOV 30-DEC 03, 1994 CL AUSTIN, TX DE GENETIC SUSCEPTIBILITY; ADDUCT; POLYMORPHISM; METABOLISM ID COKE-OVEN WORKERS; SISTER CHROMATID EXCHANGE; TRANS-STILBENE OXIDE; LUNG-CANCER; BLADDER-CANCER; GENE DELETION; CLASS-MU; SUSCEPTIBILITY; MARKER; GSTM1 AB Carcinogenic polycyclic aromatic hydrocarbons (PAHs) form DNA adducts via a complex metabolic activation pathway that includes cytochrome P450 (CYP) 1A1, whereas intermediate metabolites can be detoxified by conjugation through pathways including glutathione s-transferase M1 (GSTM1). PAH-DNA adducts can be measured in peripheral white blood cells (WBCs) and should reflect the net effect of competing activation and detoxification pathways and DNA repair as well as exposure. We have previously shown that WBC PAH-DNA adducts measured by an enzyme-linked immunosorbent assay (ELISA) were associated with recent, frequent consumption of charbroiled food among 47 nonsmoking wildland fire-fighters who provided two blood samples 8 wk apart. In the investigation reported here, which was performed in the same population, we measured the association between the GSTM1 null genotype, which results in loss of enzyme activity, and PAH-DNA adduct levels, hypothesizing that subjects with this genotype would have higher levels of DNA adducts because of their decreased ability to detoxify PAH metabolites. However, PAH-DNA adduct levels were nonsignificantly lower in subjects with the GSTM1 null genotype (n = 28) compared with other subjects (n = 19) (median 0.04 fmol/mu g DNA vs 0.07 fmol/mu g DNA, respectively, P = 0.45, Wilcoxon rank-sum test). Adduct levels were also lower in the nine subjects heterozygous or homozygous for the CYP1A1 exon 7 polymorphism (which codes for a valine rather than isoleucine and is thought to be associated with greater CYP1A1 activity) compared with the 38 wild-type subjects (P = 0.12). In the entire group, there was a positive association between consuming charbroiled food and PAH-DNA adduct formation (r = 0.24, P = 0.02, Spearman rank-order correlation). This association was weaker in the subgroup of subjects with the GSTM1 null genotype (r = 0.03, P = 0.84) and stronger among the remaining subjects (r = 0.57, P = 0.0002). These results suggest that the GSTM1 null genotype and CYP1A1 exon 7 polymorphism are not associated with increased susceptibility for PAH-DNA adduct formation in peripheral WBCs measured by ELISA in nonsmoking populations. (C) 1995 Wiley-Liss, Inc. C1 NCI,DIV CANC ETIOL,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,DIV CANC ETIOL,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. UNIV PENN,PHILADELPHIA,PA 19104. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT ENVIRONM HLTH SCI,BALTIMORE,MD. RP ROTHMAN, N (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,ENVIRONM EPIDEMIOL BRANCH,EXECUT PLAZA N,RM 418,BETHESDA,MD 20892, USA. RI Shields, Peter/I-1644-2012 FU NIEHS NIH HHS [ES03817, ES06052] NR 48 TC 57 Z9 58 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD SEP PY 1995 VL 14 IS 1 BP 63 EP 68 DI 10.1002/mc.2940140111 PG 6 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA RW551 UT WOS:A1995RW55100010 PM 7546226 ER PT J AU TRAINOR, CD EVANS, T FELSENFELD, G AF TRAINOR, CD EVANS, T FELSENFELD, G TI NEGATIVE REGULATION OF CHICKEN GATA-1 PROMOTER ACTIVITY MEDIATED BY A HORMONE RESPONSE ELEMENT SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID ERYTHROID TRANSCRIPTION FACTOR; RETINOIC ACID RECEPTORS; FACTOR COUP-TF; THYROID-HORMONE; C-ERBA; BINDING-SITE; DNA-BINDING; VITAMIN-D; A GENE; EXPRESSION AB GATA-1 is a DNA-binding protein that regulates transcription of erythroid-specific genes and is required for the formation of mature erythroid cells, We show here that the GATA-1 hormone response-like element (GHRE) within the first intron of the gene functions as an inhibitory element in chicken erythroid precursor cells, as revealed by expression studies with mutants of the minimal GATA-1 promoter. We identify in these precursor cells the relevant proteins that interact with GHRE as a heterodimer of the thyroid hormone receptor alpha and the chicken ovalbumin upstream promoter transcription factor, Our results indicate that this novel complex can negatively regulate the GATA-1 promoter and suggest that GATA-1 can overcome this inhibitory action, We provide evidence that the viral gene product, v-erb A, can also reduce GATA-1 promoter activity through the GHRE site. C1 NIDDKD, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. UNIV PITTSBURGH, DEPT BIOL SCI, PITTSBURGH, PA 15260 USA. NR 61 TC 15 Z9 15 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD SEP PY 1995 VL 9 IS 9 BP 1135 EP 1146 DI 10.1210/me.9.9.1135 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RT651 UT WOS:A1995RT65100003 PM 7491106 ER PT J AU BEITNERJOHNSON, D WERNER, H ROBERTS, CT LEROITH, D AF BEITNERJOHNSON, D WERNER, H ROBERTS, CT LEROITH, D TI REGULATION OF INSULIN-LIKE GROWTH-FACTOR-I RECEPTOR GENE-EXPRESSION BY SP1 - PHYSICAL AND FUNCTIONAL INTERACTIONS OF SP1 AT GC BOXES AND AT A CT ELEMENT SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PROMOTER REGION; BINDING-SITE; WILMS-TUMOR; TRANSCRIPTION; CLONING; PROTEIN; MODULATION; INITIATOR; PRODUCT; WT1 AB The insulin-like growth factor I (IGF-I) receptor mediates signal transduction by the IGFs and plays a critical role in growth and development, The proximal promoter region of the rat IGF-I receptor gene contains multiple Sp1 consensus-binding sites (GC boxes), Various promoter fragments fused to a luciferase reporter gene were transiently cotransfected together with an Sp1 expression vector into Drosophila Schneider cells, which lack endogenous Sp1. A proximal promoter fragment containing 476 nucleotides of 5'-flanking region and 640 nucleotides of 5'-untranslated region was strongly activated by Spl (an average of 116-fold), and progressive 5'-deletions of the promoter that sequentially removed GC boxes reduced Sp1 activation to 15-fold over basal promoter activity, DNase I footprinting studies with purified Sp1 protein revealed four GC boxes in the 5'-flanking region of the promoter and one homopurine/homopyrimidine motif (CT element) in the 5'-untranslated region that bound Sp1. Mutation of the CT element reduced Spl activation by 70%, Taken together, these results demonstrate that Spl can regulate expression of the IGF-I receptor promoter by acting both on GC boxes in the 5'-flanking region of the promoter and on a CT element in the 5'-untranslated region. C1 NIDDKD, DIABET BRANCH, BETHESDA, MD 20892 USA. OI Roberts, Charles/0000-0003-1756-5772 NR 39 TC 64 Z9 65 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD SEP PY 1995 VL 9 IS 9 BP 1147 EP 1156 DI 10.1210/me.9.9.1147 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RT651 UT WOS:A1995RT65100004 PM 7491107 ER PT J AU KUSK, P CARLSON, KE WARREN, BS HAGER, GL AF KUSK, P CARLSON, KE WARREN, BS HAGER, GL TI ROLE OF THE TATA BOX IN TRANSCRIPTION OF THE MOUSE MAMMARY-TUMOR VIRUS LONG TERMINAL REPEAT SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID RNA POLYMERASE-II; CELL-FREE TRANSCRIPTION; TRANSGENIC MICE; MMTV PROMOTER; PREINITIATION COMPLEX; NEGATIVE REGULATION; INDUCIBLE PROMOTER; HISTONE H1; ELEMENT; INVITRO AB An in vitro transcription system from mammary cells was established to study transcription of the long terminal repeat (LTR) of the mouse mammary tumor virus (MMTV). Experiments with progressive 5'-deletion constructs of the MMTV LTR revealed that a 19-base pair (bp) region from -41 to -23 bp, encompassing the TATA box and flanking DNA sequence, was as transcriptionally active as larger promoter constructs, both in nuclear extracts from human mammary cell lines (T47D and MCF7) and a nonmammary cell line (HeLa). The cell-free system was capable of supporting transcriptional induction by factors binding upstream of the TATA box, however, since purified glucocorticoid receptor-induced transcription in larger promoter constructs encompassing the MMTV hormone-responsive elements. Transcription from two other promoters, the adenovirus major late promoter and the human immunodeficiency virus LTR, also revealed a significant transcriptional contribution of upstream elements. The 19-bp TATA region from the MMTV LTR was shown to have considerably more activity in this transcription system than comparable TATA regions from other promoters. Sequences critical to the MMTV TATA region were evaluated by single base pair mutagenesis and found to comprise a consensus TATA box sequence, TATAAAA, as well as a single A just upstream of the TATAAAA sequence. Thus, the high level of basal transcription observed with the TATA region from MMTV is due to a perfect consensus TATA box sequence and a single base immediately 5' adjacent. It is likely that the high basal rate of transcription observed with this TATA box region on histone-free templates represents an inappropriate lever of basal expression and that a complete evaluation of transactivation mechanisms in this system will require the recapitulation in vitro of the chromatin-mediated repressive state that exists in vivo. C1 NCI, MOLEC VIROL LAB, BETHESDA, MD 20892 USA. NR 46 TC 7 Z9 7 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD SEP PY 1995 VL 9 IS 9 BP 1180 EP 1192 DI 10.1210/me.9.9.1180 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RT651 UT WOS:A1995RT65100007 PM 7491110 ER PT J AU SALVADORI, S ATTILA, M BALBONI, G BIANCHI, C BRYANT, SD CRESCENZI, O GUERRINI, R PICONE, D TANCREDI, T TEMUSSI, PA LAZARUS, LH AF SALVADORI, S ATTILA, M BALBONI, G BIANCHI, C BRYANT, SD CRESCENZI, O GUERRINI, R PICONE, D TANCREDI, T TEMUSSI, PA LAZARUS, LH TI DELTA-OPIOIDMIMETIC ANTAGONISTS - PROTOTYPES FOR DESIGNING A NEW-GENERATION OF ULTRASELECTIVE OPIOID-PEPTIDES SO MOLECULAR MEDICINE LA English DT Article ID RECEPTOR SELECTIVITY; DELTORPHIN-I; MOLECULAR DETERMINANTS; LIGAND-BINDING; ANALOGS; DERMORPHIN; AFFINITY; DERMENKEPHALIN; SEQUENCE; MU AB Background: Tyr-Tic (1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) and Tyr-Tic-Ala were the first peptides with delta opioid antagonist activity lacking Phe, considered essential for opioid activity based on the N-terminal tripeptide sequence (Tyr-D-Xaa-Phe) of amphibian skin opioids. Analogs were then designed to restrain the rotational flexibility of Tyr by the substitution of 2,6-dimethyl-L-tyrosine (Dmt). Materials and Methods: Tyr and Dmt peptides were synthesized by solid phase and solution methods using Fmoc technology or condensing Boc-Dmt-OH or Boc-Tyr(But)-OH with H-L-Tic-OBut or H-D-Tic-OBut, respectively. Peptides were purified (> 99%) by HPLC and characteristics determined by H-1-NMR, FAB-MS, melting point, TLC, and amino acid analyses. Results: H-Dmt-Tic-OH had high affinity (K-i(delta) = 0.022 nM) and extraordinary selectivity (K-i(mu)/K-i(delta) = 150,000); H-Dmt-Tic-Ala-OH had a K-i(delta) = 0.29 nM and delta selectivity = 20,000. Affinity and selectivity increased 8700- and 1000-fold relative to H-Tyr-Tic-OH, respectively. H-Dmt-Tic-OH and H-Dmt-Tic-NH2 fitted one-site receptor binding models (eta = 0.939-0.987), while H-Dmt-Tic-ol, H-Dmt-Tic-Ala-OH and H-Dmt-Tic-Ala-NH2 best fitted two-site models (eta = 0.708-0.801, F 18.9-26.0, p < 0.0001). Amidation increased mu affinity by 10- to 100-fold and acted synergistically with D-Tic(2) to reverse selectivity (delta --> mu). Dmt-Tic di- and tripeptides exhibited delta antagonist bioactivity (K-e = 4-66 nM) with mouse vas deferens and lacked agonist mu activity (> 10 mu M) in guinea-pig ileum preparations. Dmt-Tic analogs weakly interacted with kappa receptors in the 1 to > 20 mu M range. Conclusions: Dmt-Tic opioidmimetic peptides represent a highly potent class of opioid peptide antagonists with greater potency than the nonopioid delta antagonist naltrindole and have potential application as clinical and therapeutic compounds. C1 NIEHS,RES TRIANGLE PK,NC 27709. UNIV FERRARA,DEPT PHARMACEUT SCI,I-44100 FERRARA,ITALY. UNIV FERRARA,INST PHARMACOL,I-44100 FERRARA,ITALY. UNIV HELSINKI,DEPT PHARM,DIV PHARMACOL & TOXICOL,HELSINKI,FINLAND. UNIV NAPLES FEDERICO II,DEPT CHEM,NAPLES,ITALY. CNR,MIB,INST CHEM,I-80125 NAPLES,ITALY. RI Picone, Delia/I-5605-2012; OI Picone, Delia/0000-0002-7582-2581; Guerrini, Remo/0000-0002-7619-0918; SALVADORI, Severo/0000-0002-8224-2358 NR 60 TC 107 Z9 109 U1 0 U2 2 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 1076-1551 J9 MOL MED JI Mol. Med. PD SEP PY 1995 VL 1 IS 6 BP 678 EP 689 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA RV937 UT WOS:A1995RV93700012 PM 8529134 ER PT J AU FELDER, CC JOYCE, KE BRILEY, EM MANSOURI, J MACKIE, K BLOND, O LAI, Y MA, AL MITCHELL, RL AF FELDER, CC JOYCE, KE BRILEY, EM MANSOURI, J MACKIE, K BLOND, O LAI, Y MA, AL MITCHELL, RL TI COMPARISON OF THE PHARMACOLOGY AND SIGNAL-TRANSDUCTION OF THE HUMAN CANNABINOID CB1 AND CB2 RECEPTORS SO MOLECULAR PHARMACOLOGY LA English DT Article ID RAT-BRAIN; MESSENGER-RNA; CELLS; LOCALIZATION; ANANDAMIDE; ACTIVATION; SUBUNITS; BINDS AB The recently cloned CB2 cannabinoid receptor subtype was stably transfected into AtT-20 and Chinese hamster ovary cells to compare the binding and signal transduction properties of this receptor with those of the CB1 receptor subtype. The binding of [H-3]CP 55,940 to both CB1 and CB2 was of similar high affinity (2.6 and 3.7 nM, respectively) and saturable. In competitive binding experiments, (-)-Delta 9-tetrahydrocannabinol and CP 55,940 were equipotent at the CB1 and CB2 receptors, but WIN 55212-2 and cannabinol bound with higher affinity to the CB2 than the CB1 receptor. HU 210 had a higher affinity for the CB1 receptor. Anandamide, a recently identified endogenous cannabinoid agonist, was essentially equipotent at both receptor subtypes. The structurally related fatty acid ethanolamides dihomo-gamma-linolenylethanolamide and mead ethanolamide also bound with relatively equal affinity to both receptors, but adrenylethanolamide had a higher affinity for the CB1 receptor. The rank order of potency and efficacy for binding of the selected agonists to the CB1 and CB2 receptors was mimicked in functional inhibition of cAMP accumulation experiments for all compounds tested. Both CB1 and CB2 receptors couple to the inhibition of cAMP accumlation that was pertussis toxin sensitive. SR141716A, a CB1 receptor antagonist, was a poor antagonist at the CB2 receptor in both binding and functional inhibition of cAMP accumlation experiments. When expressed in AtT-20 cells, the CB1 receptor mediated an inhibition of Q-type calcium channels and an activation of inward rectifying potassium channels. In contrast, the CB2 receptor did not modulate the activity of either channel under identical assay conditions. Similar to results obtained for CB1 receptor, the CB2 receptor did not couple to the activation of phospholipases A(2), C, or D or to the mobilization of intracellular Ca2+. Except for its inability to couple to the modulation of Q-type calcium channels or inwardly rectifying potassium channels, the CB1 and CB2 receptors display similar pharmacological and biochemical properties. C1 UNIV WASHINGTON,DEPT PHYSIOL & ANESTHESIOL,SEATTLE,WA 98195. PANLABS INC,SEATTLE,WA 98195. NIH,HOWARD HUGHES MED INST,RES SCHOLARS PROGRAM,BETHESDA,MD 20892. RP FELDER, CC (reprint author), NIMH,CELL BIOL LAB,BLDG 36,ROOM 3A-15,36 CONVENT DR,MSC 4090,BETHESDA,MD 20892, USA. RI Mackie, Kenneth/B-7358-2011; Mackie, Ken/E-3384-2013; Mackie, Ken/E-3715-2013 OI Mackie, Ken/0000-0001-8501-6199 FU NIDA NIH HHS [DA08934, 1 R43DA09203-01]; NINDS NIH HHS [NS01588] NR 32 TC 538 Z9 550 U1 4 U2 36 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 1995 VL 48 IS 3 BP 443 EP 450 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RX635 UT WOS:A1995RX63500009 PM 7565624 ER PT J AU BLOKHIN, AV YOO, HD GERALDS, RS NAGLE, DG GERWICK, WH HAMEL, E AF BLOKHIN, AV YOO, HD GERALDS, RS NAGLE, DG GERWICK, WH HAMEL, E TI CHARACTERIZATION OF THE INTERACTION OF THE MARINE CYANOBACTERIAL NATURAL PRODUCT CURACIN-A WITH THE COLCHICINE SITE OF TUBULIN AND INITIAL STRUCTURE-ACTIVITY STUDIES WITH ANALOGS SO MOLECULAR PHARMACOLOGY LA English DT Article ID ANTIMITOTIC AGENTS; HALICHONDRIN-B; BRAIN TUBULIN; VINCA DOMAIN; BINDING; THIOCOLCHICINE; MECHANISM; RING; PODOPHYLLOTOXIN; POLYMERIZATION AB Curacin A, the major lipid constituent of a strain of the marine cyanobacterium Lyngbya majuscula obtained off the coast of Curacao, is a potent antimitotic agent that we have previously shown to inhibit microtubule assembly and colchicine binding to tubulin. In the present study, we report that curacin A probably binds in the colchicine site because it competitively inhibits the binding of [H-3]colchicine to tubulin with an apparent K-i value bf 0.6 mu M and stimulates tubulin-dependent GTP hydrolysis, as do most other colchicine-site agents. The binding of curacin A to tubulin resembled the binding reactions of combretastatin A-4 and podophyllotoxin in contrast to that of colchicine in that it occurred as extensively on ice as at higher temperatures. However, once bound, the dissociation rate of curacin A from tubulin is very slow, more closely resembling that observed with colchicinoids (thiocolchicine was the drug examined) than the faster dissociation that occurs with combretastatin A-4 and podophyllotoxin. Because the molecular structure of curacin A is so different from that of previously described colchicine-site drugs (e.g., there is no aromatic moiety, and there are only two conjugated double bonds in its linear hydrocarbon chain), we have been examining the activities of natural isomers and synthetic derivatives. So far, only modest enhancement or reduction of activity has been observed with a variety of structural changes. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. OREGON STATE UNIV,COLL PHARM,CORVALLIS,OR 97331. NR 30 TC 80 Z9 83 U1 0 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 1995 VL 48 IS 3 BP 523 EP 531 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RX635 UT WOS:A1995RX63500019 PM 7565634 ER PT J AU COMBES, RD STOPPER, H CASPARY, WJ AF COMBES, RD STOPPER, H CASPARY, WJ TI THE USE OF L5178Y MOUSE LYMPHOMA-CELLS TO ASSESS THE MUTAGENIC, CLASTOGENIC AND ANEUGENIC PROPERTIES OF CHEMICALS SO MUTAGENESIS LA English DT Article ID TK-/ MUTANTS; THYMIDINE KINASE LOCUS; MAMMALIAN-CELLS; TRIFLUOROTHYMIDINE-RESISTANT; ETHYL METHANESULFONATE; MICRONUCLEUS FORMATION; CHROMOSOME ANALYSIS; ASSAY SYSTEM; IN-VITRO; MUTATIONS AB Guidelines have been proposed to assess the potential of chemicals to affect human health, Written into these guidelines is the requirement that information be submitted on mutagenic activity, Although regulatory agencies accept mutagenicity data from both the hprt and tk loci in mammalian cells, many studies suggest that the L5178Y mouse lymphoma assay at the thymidine kinase locus is likely to detect a greater spectrum of mutagenic lesions, Thus, there is increasing emphasis being placed on this assay in many proposed and published guidelines, The L5178Y mouse lymphoma suspension protocol produces both small and large colonies which are the products of mutants growing at different rates, There is a reduction in the proportion of slowly growing mutants with respect to the total population of cells when expression is carried out in suspension, This potentially leads to quantitatively inaccurate assessments of the mutagenic activity of chemicals, Therefore an in situ procedure was developed that more accurately assesses the mutagenic activity of chemicals by maximizing the detection of small colonies, Many guidelines recommend tests that assess the clastogenic activity of chemicals. Some regulatory agencies accept data from the mouse lymphoma mutation assay to detect clastogens if the protocol is optimized for the detection of small colonies or if colony sizing data are submitted, The conventional suspension assay protocol is not sufficiently validated for this purpose. The in situ protocol has greater potential to meet these requirements, However, although this strategy might be suitable for detecting compounds that induce gene mutations and chromosomal aberrations in cells, it should not be used to distinguish these two responses from each other because there are insufficient data showing that small and large colony populations always represent the induction of chromosome aberrations and gene mutations, respectively, It is, nevertheless, possible to infer not only mutation and clastogenesis but also aneugenesis in one culture using mouse lymphoma cells, To achieve this, we recommend an assessment of micronucleus formation with an analysis of micronuclei for the presence of whole chromosomes and chromosomal fragments in mouse lymphoma cells coupled with the measurement of TFT resistance using the in situ protocol with these same cells, This should result in eventual validation of a simpler and more accurate method for ascertaining these endpoints. C1 UNIV WURZBURG,INST PHARMACOL & TOXICOL,W-8700 WURZBURG,GERMANY. FUND REPLACEMENT ANIM MED EXPT,NOTTINGHAM NG1 4EE,ENGLAND. NATL INST HLTH,ENVIRONM CARCINOGENESIS & MUTAGENESIS LAB,RES TRIANGLE PK,NC 27709. NR 68 TC 29 Z9 31 U1 1 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD SEP PY 1995 VL 10 IS 5 BP 403 EP 408 DI 10.1093/mutage/10.5.403 PG 6 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA RX880 UT WOS:A1995RX88000005 PM 8544753 ER PT J AU POMMIER, Y JENKINS, J KOHLHAGEN, G LETEURTRE, F AF POMMIER, Y JENKINS, J KOHLHAGEN, G LETEURTRE, F TI DNA RECOMBINASE ACTIVITY OF EUKARYOTIC DNA TOPOISOMERASE-I - EFFECTS OF CAMPTOTHECIN AND OTHER INHIBITORS SO MUTATION RESEARCH-DNA REPAIR LA English DT Article DE DNA STRAND TRANSFER; CANCER CHEMOTHERAPY; ILLEGITIMATE RECOMBINATION; SAINTOPIN ID SV40 DNA; RELIGATION REACTIONS; CLEAVABLE COMPLEXES; REPLICATION FORKS; MAMMALIAN-CELLS; STRAND TRANSFER; SEQUENCE; INDUCTION; BREAKAGE; SITES AB DNA oligonucleotides containing a strong topoisomerase I cleavage site were used to study the DNA cleavage and strand transferase activities of calf thymus topoisomerase I (top1) in the absence and presence of camptothecin. A partially single-stranded oligonucleotide with only two nucleotides on the 3' side of the cleavage site (positions +1 and +2) was cleaved at the same position as the corresponding duplex oligonucleotide. However, cleavage in the absence of camptothecin was more pronounced than in the duplex oligonucleotide and was only partially reversible in the presence of 0.5 M NaCl, consistent with release of the dinucleotide 3' to the top1 break. Another reaction took place generating a larger DNA fragment which resulted from religation (strand transfer) of the 5'-hydroxyl terminus of the non-scissile DNA strand to the 3' end of the top1-linked oligonucleotide after loss of the +1 and +2 nucleotides. Top1 religation activity appeared efficient since only the last 5' base of the single-stranded DNA acceptor was complementary to the 3' tail of the donor DNA, Religation was not detectable with a double-stranded DNA acceptor, which is consistent with the persistence of top1-induced DNA double-strand breaks in camptothecin-treated cells. Camptothecin and other top1 inhibitors enhanced cleavage in both the partially single-stranded and the duplex oligonucleotides, indicating that they did not inhibit the induction of top1-mediated DNA cleavage but primarily blocked the religation step of the enzyme catalytic cycle. The top1 DNA strand transferase activity was reversibly inhibited by camptothecin and several derivatives, as well as saintopin. These results are discussed in terms of camptothecin-induced DNA recombinations. RP POMMIER, Y (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BLDG 37,RM 5C25,BETHESDA,MD 20892, USA. NR 38 TC 42 Z9 42 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8777 J9 MUTAT RES-DNA REPAIR JI Mutat. Res.-DNA Repair PD SEP PY 1995 VL 337 IS 2 BP 135 EP 145 DI 10.1016/0921-8777(95)00019-G PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA TC165 UT WOS:A1995TC16500007 PM 7565862 ER PT J AU MIRVISH, SS HUANG, Q WILLIAMSON, J CHEN, SC GELBOIN, HV AF MIRVISH, SS HUANG, Q WILLIAMSON, J CHEN, SC GELBOIN, HV TI USE OF MONOCLONAL-ANTIBODIES TO CYTOCHROME P450S TO INDICATE THE CRITICAL DEALKYLATION AND THE P450S INVOLVED IN METHYL-N-AMYLNITROSAMINE MUTAGENICITY IN THE PRESENCE OF INDUCED RAT-LIVER MICROSOMES SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE METHYL-N-AMYLNITROSAMINE; MUTAGENICITY; AMES TEST; DEALKYLATION; MONOCLONAL ANTIBODY; CYTOCHROME; P450 ID DNA METHYLATION; SALMONELLA-TYPHIMURIUM; ALIPHATIC NITROSAMINES; HYDROXY DERIVATIVES; METABOLISM; ESOPHAGUS; ISOZYMES; NITROSOMETHYLAMYLAMINE; NITROSODIMETHYLAMINE; CARCINOGENESIS AB The mutagenicity for Salmonella typhimurium TA 1535 of the carcinogen methyl-n-amylnitrosamine (MNAN) was examined in the presence of rat liver microsomes from uninduced and induced rats. The number of mutations followed the order phenobarbital- and Aroclor-induced > 3-methylcholanthrene- and isoniazid-induced > uninduced microsomes. The MNAN metabolite 4-hydroxy-MNAN was not mutagenic. Using each type of induced liver microsomes, we examined the effect on MNAN mutagenicity of four monoclonal antibodies (MAbs) that inhibit cytochrome P450s. The MAbs inhibited MNAN mutagenicity in seven MAb-microsome combinations by up to 49%. Taken together, these results indicated that CYP (P450) 2B1/2B2 was responsible for one half and CYP 2C11 for one quarter of MNAN mutagenicity with phenobarbital-induced microsomes, CYP 1A1/1A2 accounted for about 40% of the mutagenicity with 3-methylcholanthrene-induced microsomes, CYP 2B1/2B2 accounted for half and CYP 1A1/1A2 and 2C11 for smaller proportions of the mutagenicity with Aroclor-induced microsomes, and CYP 1A1/1A2 accounted for about 30% of the mutagenicity with isoniazid-induced microsomes. With isoniazid-induced microsomes, MAb 2-66-3 to CYP 2B1/2B1 caused an unexpected 219% increase and MAb 1-68-11 caused a moderate increase in MNAN mutagenicity. The test MAbs also inhibited the microsome-catalyzed demethylation and depentylation of MNAN by up to 83%, confirming previous results. Four comparisons between individual mutagenic and metabolic results supported the view that depentylation of MNAN was more critical for its mutagenicity than was demethylation, e.g., with 3-methylcholanthrene- and Aroclor-induced microsomes, MAb 1-7-1 to CYP 1A1/1A2 inhibited mutagenesis and depentylation, but did not affect demethylation. C1 UNIV NEBRASKA,MED CTR,DEPT PHARMACEUT SCI,OMAHA,NE 68198. UNIV NEBRASKA,MED CTR,DEPT BIOCHEM,OMAHA,NE 68198. NCI,BETHESDA,MD 20892. RP MIRVISH, SS (reprint author), UNIV NEBRASKA,MED CTR,EPPLEY INST RES CANC,OMAHA,NE 68198, USA. FU NCI NIH HHS [CA-36727, R01-CA-35628] NR 39 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD SEP PY 1995 VL 331 IS 1 BP 161 EP 170 DI 10.1016/0027-5107(95)00065-Q PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA RU973 UT WOS:A1995RU97300015 PM 7666863 ER PT J AU MARQUIS, ST RAJAN, JV WYNSHAWBORIS, A XU, TJ YIN, GY ABEL, KJ WEBER, BL CHODOSH, LA AF MARQUIS, ST RAJAN, JV WYNSHAWBORIS, A XU, TJ YIN, GY ABEL, KJ WEBER, BL CHODOSH, LA TI THE DEVELOPMENTAL PATTERN OF BRCA1 EXPRESSION IMPLIES A ROLE IN DIFFERENTIATION OF THE BREAST AND OTHER TISSUES SO NATURE GENETICS LA English DT Article ID CELLULAR TUMOR-ANTIGEN; FAMILIAL BREAST; GENE-EXPRESSION; OVARIAN-CANCER; P53; LACTOFERRIN AB We have examined the developmental expression of the murine breast and ovarian cancer susceptibility gene, Brca1, to investigate its role in the control of cell growth and differentiation. Specifically, we have analysed Brca1 expression during embryonic development, in adult tissues, and during postnatal mammary gland development, particularly in response to ovarian hormones. Our results suggest that Brca1 is expressed in rapidly proliferating cell types undergoing differentiation. In the mammary gland, Brca1 expression is induced during puberty, pregnancy, and following treatment of ovariectomized animals with 17 beta-estradiol and progesterone. These observations imply that Brca1 is involved in the processes of proliferation and differentiation in multiple tissues, notably in the mammary gland in response to ovarian hormones. C1 UNIV PENN,SCH MED,DEPT MOLEC & CELLULAR ENGN,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,INST HUMAN GENE THERAPY,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT INTERNAL MED,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT GENET,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DIV ENDOCRINOL DIABET & METAB,PHILADELPHIA,PA 19104. NIH,NATL CTR HUMAN GENOME RES,GENET DIS RES LAB,BETHESDA,MD 20892. UNIV MICHIGAN,SCH MED,DEPT HUMAN GENET,ANN ARBOR,MI 48109. FU NCI NIH HHS [1P20CA66179, CA57601] NR 29 TC 299 Z9 303 U1 0 U2 8 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 SEP PY 1995 VL 11 IS 1 BP 17 EP 26 DI 10.1038/ng0995-17 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA RR728 UT WOS:A1995RR72800010 PM 7550308 ER PT J AU LENZ, FA GRACELY, RH ROMANOSKI, AJ HOPE, EJ ROWALAND, LH DOUGHERTY, PM AF LENZ, FA GRACELY, RH ROMANOSKI, AJ HOPE, EJ ROWALAND, LH DOUGHERTY, PM TI STIMULATION IN THE HUMAN SOMATOSENSORY THALAMUS CAN REPRODUCE BOTH THE AFFECTIVE AND SENSORY DIMENSIONS OF PREVIOUSLY EXPERIENCED PAIN SO NATURE MEDICINE LA English DT Article ID RESPONSES; NEURONS; MICROSTIMULATION; SENSATIONS; NUCLEUS; MONKEYS; AREA AB Thalamic structures involved in the unpleasant emotional or affective aspect of pain are poorly understood. We now describe studies of the region of the thalamic principal somatosensory nucleus (Vc) performed before thalamotomy for tremor in a patient who also had panic disorder. Microstimulation in the region posterior to Vc evoked chest pain, including a strong affective dimension, almost identical to that occurring during his panic attacks, as measured using a questionnaire. Results in our other patients indicate that stimulation-associated pain with a strong affective dimension occurred only in those patients who had previously experienced spontaneous pain with a strong affective component. These results are consistent with stimulation-evoked activation of limbic structures, which are connected through cortex with the region posterior to Vc and involved in the affective dimension of pain through conditioning by previous experience. C1 JOHNS HOPKINS UNIV, DEPT PSYCHIAT, BALTIMORE, MD 21287 USA. JOHNS HOPKINS UNIV, DEPT CARDIOL, BALTIMORE, MD 21287 USA. NIDR, NEUROBIOL & ANESTHESIOL BRANCH, BETHESDA, MD 20892 USA. RP JOHNS HOPKINS UNIV, DEPT NEUROSURG, MEYER BLDG 7-113, 600 N WOLFE ST, BALTIMORE, MD 21287 USA. RI Frank, David/E-8213-2012; OI Dougherty, Patrick/0000-0002-2177-2734 FU NINDS NIH HHS [K08 NS 01384, NS 28598, P01 NS 32386] NR 38 TC 56 Z9 57 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD SEP PY 1995 VL 1 IS 9 BP 910 EP 913 DI 10.1038/nm0995-910 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA RT303 UT WOS:A1995RT30300044 PM 7585216 ER PT J AU ORAVECZ, T RODERIQUEZ, G KOFFI, J WANG, JH DITTO, M BOUHABIB, DC LUSSO, P NORCROSS, MA AF ORAVECZ, T RODERIQUEZ, G KOFFI, J WANG, JH DITTO, M BOUHABIB, DC LUSSO, P NORCROSS, MA TI CD26 EXPRESSION CORRELATES WITH ENTRY, REPLICATION AND CYTOPATHICITY OF MONOCYTOTROPIC HIV-1 STRAINS IN A T-CELL LINE SO NATURE MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; DIPEPTIDYL PEPTIDASE-IV; ACTIVATION ANTIGEN; BIOLOGICAL PHENOTYPE; AIDS VIRUS; HTLV-III; INFECTION; SURFACE; CD4; INDIVIDUALS AB Experiments to identify cell determinants involved in HIV-1 tropism revealed a specific decrease in the expression of the T-cell activation antigen CD26 after monocytotropic (M-tropic) but not T-cell line-tropic (T-tropic) virus infection of the PM1 T-cell line. The level of CD26 expression in single-cell clones of PM1 correlated with the entry rate and cytopathicity of M-tropic HIV-1 variants, resulting in preferential survival of cells with low CD26 levels after infection. Experiments with recombinant viruses showed that the third hypervariable region of the envelope gp120 plays an important role in this selection process. This study identifies CD26 as a key marker for M-tropic human immunodeficiency virus type 1 (HIV-1) infection and suggests a mechanism for the early loss of CD26-expressing cells in HIV-1-infected individuals. C1 NIH,FOOD & DRUG ADM,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892. UNIV MILAN,OSPED L SACCO,INST MALATTIE INFETT,I-20132 MILAN,ITALY. NR 45 TC 61 Z9 61 U1 1 U2 1 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 1995 VL 1 IS 9 BP 919 EP 926 DI 10.1038/nm0995-919 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA RT303 UT WOS:A1995RT30300046 PM 7585218 ER PT J AU GRAINGER, DJ WAKEFIELD, L BETHELL, HW FARNDALE, RW METCALFE, JC AF GRAINGER, DJ WAKEFIELD, L BETHELL, HW FARNDALE, RW METCALFE, JC TI RELEASE AND ACTIVATION OF PLATELET LATENT TGF-BETA IN BLOOD-CLOTS DURING DISSOLUTION WITH PLASMIN SO NATURE MEDICINE LA English DT Article ID GROWTH-FACTOR-BETA; MOLECULAR-WEIGHT COMPLEX; SMOOTH-MUSCLE CELLS; FACTOR-BETA-1; PROLIFERATION; TGF-BETA-1; SEQUENCES; BINDING; PROTEIN AB Transforming growth factor beta 1 (TGF-beta 1) is a platelet-derived cytokine involved in both normal wound healing and scarring. We show that human platelets contain two pools of latent TGF-beta 1, which constitute more than 95% of the total TGF-beta assayed in whole platelets. During clotting, one pool, the large latent TGF-beta complex consisting of latent TGF-beta binding protein (LTBP), the latency-associated peptide (LAP) and the 25-kD mature TGF-beta 1 dimer is released into the serum. A second pool, which contains LAP but not LTBP, is retained in the clot, but can be released by RGD peptide. When the clot is dissolved by plasmin this bound TGF-beta 1 is gradually activated and released. if similar mechanisms operate in vivo, the clot will act as a slow-release capsule of TGF-beta 1 activity during wound healing. C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. RP GRAINGER, DJ (reprint author), UNIV CAMBRIDGE,DEPT BIOCHEM,TENNIS COURT RD,CAMBRIDGE CB2 1QW,ENGLAND. NR 28 TC 157 Z9 160 U1 0 U2 3 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 1995 VL 1 IS 9 BP 932 EP 937 DI 10.1038/nm0995-932 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA RT303 UT WOS:A1995RT30300048 PM 7585220 ER PT J AU KUBONIWA, H TJANDRA, N GRZESIEK, S REN, H KLEE, CB BAX, A AF KUBONIWA, H TJANDRA, N GRZESIEK, S REN, H KLEE, CB BAX, A TI SOLUTION STRUCTURE OF CALCIUM-FREE CALMODULIN SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID TROPONIN-C; PEPTIDE COMPLEX; SEQUENTIAL ASSIGNMENT; BACKBONE DYNAMICS; NMR-SPECTROSCOPY; PROTEINS; SPECTRA; N-15; RESOLUTION; RECOGNITION AB The three-dimensional structure of calmodulin in the absence of Ca2+ has been determined by three- and four-dimensional heteronuclear NMR experiments, including ROE, isotope-filtering combined with reverse labelling, and measurement of more than 700 three-bond I-couplings. In analogy with the Ca2+-ligated state of this protein, it consists of two small globular domains separated by a flexible linker, with no stable, direct contacts between the two domains. In the absence of Ca2+, the four helices in each of the two globular domains form a highly twisted bundle, capped by a short anti-parallel beta-sheet. This arrangement is qualitatively similar to that observed in the crystal structure of the Ca2+-free N-terminal domain of troponin C. C1 NIDDKD,PHYS CHEM LAB,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 43 TC 517 Z9 522 U1 5 U2 47 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD SEP PY 1995 VL 2 IS 9 BP 768 EP 776 DI 10.1038/nsb0995-768 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA TD552 UT WOS:A1995TD55200016 PM 7552748 ER PT J AU BENNETT, MC FORDYCE, DE ROSE, GM WEHNER, JM AF BENNETT, MC FORDYCE, DE ROSE, GM WEHNER, JM TI CHRONIC SODIUM-AZIDE TREATMENT DECREASES MEMBRANE-BOUND PROTEIN-KINASE-C ACTIVITY IN THE RAT HIPPOCAMPUS SO NEUROBIOLOGY OF LEARNING AND MEMORY LA English DT Note ID ALZHEIMERS-DISEASE; CYTOCHROME-OXIDASE; TRANSLOCATION; BRAIN AB Chronic administration of sodium azide in rats inhibits cytochrome oxidase and produces learning and memory deficits. The present experiment tested the hypothesis that chronic sodium azide treatment might also alter protein kinase C activation. Continuous infusion of sodium azide (400 mu g/h, sc) in rats for 2 weeks significantly decreases membrane-bound protein kinase C in hippocampus, but not frontal cortex, temporal cortex, or cerebellum. Since protein kinase C activation is correlated with hippocampus-dependent learning, these results suggest a possible biochemical mechanism for azide-induced impairment of learning. (C) 1995 Academic Press, Inc. C1 UNIV COLORADO,DEPT BEHAV GENET,BOULDER,CO 80309. NIA,NEUROSCI LAB,BETHESDA,MD 20892. UNIV COLORADO,HLTH SCI CTR,DEPT PHARMACOL,DENVER,CO 80220. UNIV COLORADO,HLTH SCI CTR,NEUROSCI TRAINING PROGRAM,DENVER,CO 80220. VET ADM MED CTR,MED RES SERV,DENVER,CO 80220. FU NIA NIH HHS [AG10755]; NIMH NIH HHS [NIMH-48663]; NINDS NIH HHS [NS-09169] NR 20 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 1074-7427 J9 NEUROBIOL LEARN MEM JI Neurobiol. Learn. Mem. PD SEP PY 1995 VL 64 IS 2 BP 187 EP 190 DI 10.1006/nlme.1995.1058 PG 4 WC Behavioral Sciences; Neurosciences; Psychology; Psychology, Multidisciplinary SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA RP778 UT WOS:A1995RP77800011 PM 7582827 ER PT J AU VANECEK, J KLEIN, DC AF VANECEK, J KLEIN, DC TI MECHANISM OF MELATONIN SIGNAL-TRANSDUCTION IN THE NEONATAL RAT PITUITARY SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article; Proceedings Paper CT International Symposium on Eye-Pineal Relationships CY SEP 21-25, 1994 CL LODZ, POLAND ID GONADOTROPIN-RELEASING HORMONE; CELLS; CALCIUM; INHIBITION; CYCLASE; PROTEIN; BINDING; CA-2+; CAMP AB Melatonin inhibits GnRH-induced LH release from anterior pituitary of the neonatal rat. It acts via specific high affinity receptors and decreases concentrations of intracellular calcium ([Ca2+](i)) and cyclic AMP. To determine which of these second messengers transduces the melatonin inhibition of LH release, we have tested the effect of melatonin in the presence of specific drugs affecting either of these second messengers. Calcium channel antagonist nifedipine inhibited LH release from cultured pituitary to a similar degree as did melatonin and prevented the inhibitory effect of melatonin on LH release. Calcium channel agonist Bay K potentiated the LH release and reduced the inhibitory effect of melatonin. This observation constitutes strong evidence that melatonin inhibits LK release aia inhibition of calcium influx through voltage sensitive channels. The cyclic AMP derivative 8-bromo-cAMP potentiated GnRH-stimulation of LH release but did not prevent the melatonin-induced inhibition of the release. However, when used in combination with low concentration of Bay K, which alone reduced the melatonin effect only partially, 8-bromo-cAMP completely blocked the melatonin effect. This observation suggests that both cAMP and [Ca2+](i) may be involved in the effect of melatonin on LH release. C1 NICHHD,DEV NEUROBIOL LAB,NEUROENDOCRINOL SECT,BETHESDA,MD 20892. RP VANECEK, J (reprint author), ACAD SCI CZECH REPUBL,INST PHYSIOL,VIDENSKA 1083,CR-14220 PRAGUE 4,CZECH REPUBLIC. NR 21 TC 19 Z9 20 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD SEP PY 1995 VL 27 IS 3 BP 273 EP 278 DI 10.1016/0197-0186(95)00032-4 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA RT741 UT WOS:A1995RT74100007 PM 8520466 ER PT J AU CASEY, BJ COHEN, JD JEZZARD, P TURNER, R NOLL, DC TRAINOR, RJ GIEDD, J KAYSEN, D HERTZPANNIER, L RAPOPORT, JL AF CASEY, BJ COHEN, JD JEZZARD, P TURNER, R NOLL, DC TRAINOR, RJ GIEDD, J KAYSEN, D HERTZPANNIER, L RAPOPORT, JL TI ACTIVATION OF PREFRONTAL CORTEX IN CHILDREN DURING A NONSPATIAL WORKING-MEMORY TASK WITH FUNCTIONAL MRI SO NEUROIMAGE LA English DT Article ID VISUAL-CORTEX; STIMULATION; COMPONENT AB Functional magnetic resonance imaging (fMRI) was used to examine the pattern of activity of prefrontal cortex in prepubertal children during performance of a nonspatial working memory task. The children observed sequences of letters and responded whenever a letter repeated with exactly one nonidentical letter intervening. In a comparison task, subjects monitored similar sequences of letters for any occurrence of a single, prespecified target letter. Location of activation closely approximated that observed in a recent fMRI study with adults using exactly the same task. Activation of the inferior and middle frontal gyri was reliably observed within individual subjects during performance of the working memory task relative to the comparison task. Activation increased and decreased with a time course that was highly consistent with the task manipulations and correlated with behavioral performance. To our knowledge, this study is one of the first to demonstrate the applicability of fMRI to a normative developmental population. Issues of age dependence of the hemodynamic responses of fMRI are discussed. (C) 1995 Academic Press, Inc. C1 UNIV PITTSBURGH,DEPT RADIOL,PITTSBURGH,PA 15213. CARNEGIE MELLON UNIV,DEPT PSYCHOL,PITTSBURGH,PA 15213. CARNEGIE MELLON UNIV,DEPT COMP SCI,PITTSBURGH,PA 15213. NHLBI,BETHESDA,MD 20892. NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. INST CHILD HLTH,RCS BIOPHYS UNIT,LONDON,ENGLAND. RP CASEY, BJ (reprint author), UNIV PITTSBURGH,DEPT PSYCHIAT,3811 OHARA ST,PITTSBURGH,PA 15213, USA. RI Giedd, Jay/A-3080-2008; Turner, Robert/C-1820-2008; Giedd, Jay/B-7302-2012; Noll, Douglas/D-8124-2014; Giedd, Jay/J-9644-2015; OI Giedd, Jay/0000-0003-0827-3460; Noll, Douglas/0000-0002-0983-3805; Giedd, Jay/0000-0003-2002-8978; Jezzard, Peter/0000-0001-7912-2251 NR 40 TC 227 Z9 233 U1 2 U2 14 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD SEP PY 1995 VL 2 IS 3 BP 221 EP 229 DI 10.1006/nimg.1995.1029 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA RX056 UT WOS:A1995RX05600007 PM 9343606 ER PT J AU Catania, A Suffredini, AF Lipton, JM AF Catania, A Suffredini, AF Lipton, JM TI Endotoxin causes release of alpha-melanocyte-stimulating hormone in normal human subjects SO NEUROIMMUNOMODULATION LA English DT Article DE alpha-melanocyte stimulating hormone; adrenocorticotropin hormone; tumor necrosis factor; endotoxemia ID PITUITARY-ADRENAL AXIS; TUMOR NECROSIS FACTOR; MSH PEPTIDES; FEVER; RABBIT AB The neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH), a proopiomelanocortin derivative, is a potent modulator of fever, inflammation, and other aspects of the acute-phase response. alpha-MSH concentrations increase in rabbit plasma after large doses of endotoxin, but it is not known if changes in this potent peptide likewise occur during endotoxemia in humans. The current study was performed to assess changes in plasma alpha-MSH during the acute inflammatory response to endotoxin in normal humans. alpha-MSH was measured in plasma samples obtained over a 5-hour study period in 20 normal human subjects given endotoxin. Plasma adrenocorticotropic hormone (ACTH) and tumor necrosis factor were also measured at the same time points. Endotoxin administration caused fever-related increases in plasma alpha-MSH. Five subjects with a high thermal response to endotoxin (> 2.6 degrees C above baseline) showed a 2- to 4-fold increase in circulating alpha-MSH whereas subjects with lower fever (< 2.3 degrees C) did not. Tumor necrosis factor was detected in all subjects after endotoxin, but its peak was significantly less (p < 0.01) in those subjects who had substantial increases in alpha-MSH. Plasma ACTH increased in all subjects given endotoxin, but unlike its 1-13 derivative alpha-MSH, the increases were not commensurate with fever. The data show that challenge with endotoxin causes alpha-MSH release in normal human subjects with high fever. The positive relationship between increases in circulating alpha-MSH and high thermal response together with previous evidence from animal studies suggests that the neuropeptide is an endogenous modulator of host responses. C1 NIH,DEPT CRIT CARE MED,BETHESDA,MD 20892. UNIV TEXAS,SW MED CTR,DEPT PHYSIOL,DALLAS,TX 75235. UNIV TEXAS,SW MED CTR,DEPT ANESTHESIOL,DALLAS,TX 75235. RP Catania, A (reprint author), UNIV MILAN,MED CLIN 1,VIA F SFORZA 35,I-20122 MILAN,ITALY. FU NINDS NIH HHS [NS 10046] NR 33 TC 28 Z9 30 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PD SEP-OCT PY 1995 VL 2 IS 5 BP 258 EP 262 DI 10.1159/000097204 PG 5 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA UK727 UT WOS:A1995UK72700002 PM 8739198 ER PT J AU WICHMAN, A SANDLER, AL AF WICHMAN, A SANDLER, AL TI RESEARCH INVOLVING SUBJECTS WITH DEMENTIA AND OTHER COGNITIVE IMPAIRMENTS - EXPERIENCE AT THE NIH, AND SOME UNRESOLVED ETHICAL CONSIDERATIONS SO NEUROLOGY LA English DT Article RP WICHMAN, A (reprint author), NCI,OFF HUMAN SUBJECTS RES,BLDG 10,ROOM 1C-116,10 CTR DR MSC 1154,BETHESDA,MD 20892, USA. NR 6 TC 7 Z9 7 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 SEP PY 1995 VL 45 IS 9 BP 1777 EP 1778 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA RV379 UT WOS:A1995RV37900028 PM 7675247 ER PT J AU VALENZUELA, DM STITT, TN DISTEFANO, PS ROJAS, E MATTSSON, K COMPTON, DL NUNEZ, L PARK, JS STARK, JL GIES, DR THOMAS, S LEBEAU, MM FERNALD, AA COPELAND, NG JENKINS, NA BURDEN, SJ GLASS, DJ YANCOPOULOS, GD AF VALENZUELA, DM STITT, TN DISTEFANO, PS ROJAS, E MATTSSON, K COMPTON, DL NUNEZ, L PARK, JS STARK, JL GIES, DR THOMAS, S LEBEAU, MM FERNALD, AA COPELAND, NG JENKINS, NA BURDEN, SJ GLASS, DJ YANCOPOULOS, GD TI RECEPTOR TYROSINE KINASE SPECIFIC FOR THE SKELETAL-MUSCLE LINEAGE - EXPRESSION IN EMBRYONIC MUSCLE, AT THE NEUROMUSCULAR-JUNCTION, AND AFTER INJURY SO NEURON LA English DT Article ID PERONEAL MUSCULAR-ATROPHY; ACETYLCHOLINE-RECEPTOR; GROWTH-FACTOR; FAMILY; PROTEIN; DOMAIN; DIFFERENTIATION; IDENTIFICATION AB While a number of growth factors have been described that are highly specific for particular cell lineages, neither a factor nor a receptor uniquely specific to the skeletal muscle lineage has previously been described. Here we identify a receptor tyrosine kinase (RTK) specific to skeletal muscle, which we term ''MuSK'' for muscle-specific kinase. MuSK is expressed at low levels in proliferating myoblasts and is induced upon differentiation and fusion, In the embryo, it is specifically expressed in early myotomes and developing muscle. MUSK is then dramatically down-regulated in mature muscle, where it remains prominent only at the neuromuscular junction; MuSK is thus the only known RTK that localizes to the neuromuscular junction. Strikingly, MuSK expression is dramatically induced throughout the adult myofiber after denervation, block of electrical activity, or physical immobilization. In humans, MuSK maps to chromosome 9q31.3-32, which overlaps with the region reported to contain the Fukuyama muscular dystrophy mutation. Identification of MUSK introduces a novel receptor-factor system that seems sure to play an important and selective role in many aspects of skeletal muscle development and function. C1 NYU, MED CTR, SKIRBALL INST, NEW YORK, NY 10016 USA. UNIV CHICAGO, DEPT MED, HEMATOL ONCOL SECT, CHICAGO, IL 60637 USA. NATL CANC INST, FREDERICK CANC RES CTR, ABL BASIC RES PROGRAM, MAMMALIAN GENET LAB, FREDERICK, MD 21703 USA. RP REGENERON PHARMACEUT INC, 777 OLD SAW MILL RIVER RD, TARRYTOWN, NY 10591 USA. FU NCI NIH HHS [CA 40046] NR 41 TC 303 Z9 308 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD SEP PY 1995 VL 15 IS 3 BP 573 EP 584 DI 10.1016/0896-6273(95)90146-9 PG 12 WC Neurosciences SC Neurosciences & Neurology GA RV945 UT WOS:A1995RV94500011 PM 7546737 ER PT J AU BHAGWAT, SV LEELAVATHI, BC SHANKAR, SK BOYD, MR RAVINDRANATH, V AF BHAGWAT, SV LEELAVATHI, BC SHANKAR, SK BOYD, MR RAVINDRANATH, V TI CYTOCHROME-P450 AND ASSOCIATED MONOOXYGENASE ACTIVITIES IN THE RAT AND HUMAN SPINAL-CORD - INDUCTION, IMMUNOLOGICAL CHARACTERIZATION AND IMMUNOCYTOCHEMICAL LOCALIZATION SO NEUROSCIENCE LA English DT Article ID HUMAN-BRAIN; INDUCIBLE CYTOCHROME-P-450; REGIONAL DISTRIBUTION; MULTIPLE FORMS; ACTIVATION; P-450; QUANTITATION; METABOLISM; CHEMICALS; PROTEINS AB We have discovered cytochrome P450 and associated monooxygenase activities in microsomes prepared from spinal cord tissues from rats and a human. Cytochrome P450 levels and nicotinamide adenine dinucleotide phosphate cytochrome c reductase activities in microsomes from rat spinal cord were similar to those observed from the whole brain. However, certain monooxygenase activities were significantly lower in the rat spinal cord microsomes as compared to the corresponding activities observed in the whole brain. Cytochrome P450-mediated monooxygenase activities were also detectable in microsomes prepared from human spinal cord. Immunoblot analyses of rat and human spinal cord microsomes using antisera to various forms of hepatic cytochrome P450 namely (2B1 + 2B2), 1A1, 1A2 and 2E1 revealed the presence of immunologically similar forms. The spinal cord microsomes also cross-reacted with the antiserum to the phenobarbital-inducible form of rat brain cytochrome P450. Immunocytochemical stain was predominant in the gray horns of the rat spinal cord. At the cervical level, lamina 1 and 2 representing the substantia gelatinosa were intensely stained. In the ventral horns, lamina 7, 8 and 9 containing the large motor neurons were strongly labelled, while small neurons revealed variable staining. In the white matter, the glial cells were stained but the axons remained non-reactive. Because of the known roles of in situ cytochrome P450-mediated metabolism in the local expression of toxic effects of numerous chemicals in diverse cells and tissues of the body, and the present demonstration of multiple forms of cytochrome P450 and associated metabolic activities in the spinal cord, further consideration of the potential role of cytochrome P450-mediated bioactivation of environmental toxicants in the pathogenesis of neurodegenerative disorders is warranted. C1 NATL INST MENTAL HLTH & NEUROSCI,DEPT NEUROCHEM,BANGALORE 560029,KARNATAKA,INDIA. NATL INST MENTAL HLTH & NEUROSCI,DEPT NEUROPATHOL,BANGALORE 560029,KARNATAKA,INDIA. NCI,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21701. NR 28 TC 16 Z9 19 U1 0 U2 0 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 SEP PY 1995 VL 68 IS 2 BP 593 EP 601 DI 10.1016/0306-4522(95)00071-P PG 9 WC Neurosciences SC Neurosciences & Neurology GA RL983 UT WOS:A1995RL98300030 PM 7477969 ER PT J AU PODURI, A BEASONHELD, LL MOSS, MB ROSENE, DL HYMAN, BT AF PODURI, A BEASONHELD, LL MOSS, MB ROSENE, DL HYMAN, BT TI CA3 NEURONAL DEGENERATION FOLLOWS CHRONIC ENTORHINAL CORTEX LESIONS SO NEUROSCIENCE LETTERS LA English DT Article DE NEURODEGENERATION; ENTORHINAL CORTEX LESIONS; HIPPOCAMPUS; STEREOLOGY AB Entorhinal cortex lesions are a common experimental paradigm to study memory function and neural plasticity after hippocampal deafferentation, The long term consequences of such lesions are of particular interest both in the context of these models and because pathological changes of Alzheimer's disease destroy entorhinal cortex projection neurons. We used stereological counting techniques to assess the structural integrity of the hippocampal formation 0.5-28 months after entorhinal lesion in the rhesus monkey. Surprisingly, 18-28 months after lesion the number of CA3 neurons was decreased by 57%, while neuron numbers in other subfields did not change. These results suggest that delayed transsynaptic neural degeneration can occur long after brain injury. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. BOSTON UNIV,SCH MED,DEPT ANAT & NEUROBIOL,BOSTON,MA 02118. NIA,NEUROSCI LAB,BETHESDA,MD 20892. RI Rosene, Douglas/G-1973-2015 FU NIA NIH HHS [AG08487, AG00001] NR 15 TC 18 Z9 18 U1 0 U2 2 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 1 PY 1995 VL 197 IS 1 BP 1 EP 4 DI 10.1016/0304-3940(95)11879-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA RV602 UT WOS:A1995RV60200001 PM 8545043 ER PT J AU YASUI, M OTA, K GARRUTO, RM AF YASUI, M OTA, K GARRUTO, RM TI EFFECTS OF CALCIUM-DEFICIENT DIETS ON MANGANESE DEPOSITION IN THE CENTRAL-NERVOUS-SYSTEM AND BONES OF RATS SO NEUROTOXICOLOGY LA English DT Article DE MANGANESE; ALUMINUM; CALCIUM-DEFICIENT DIETS; CENTRAL NERVOUS SYSTEM; BONE ID AMYOTROPHIC-LATERAL-SCLEROSIS; POSITRON EMISSION TOMOGRAPHY; NEURODEGENERATIVE DISORDERS; TRACE-ELEMENTS; BRAIN BARRIER; METABOLISM; MAGNESIUM; EXPOSURE; MONKEYS; TISSUES AB The presence of both aluminum (Al) and manganese (Mn) in central nervous system tissues (CNS) has been reported in Parkinson's disease and in parkinsonism-dementia (PD) on Guam. Epidemiological surveys on Guam have suggested that low calcium (Ca), magnesium (Mg) and high Al and Mn in river, soil and drinking water may be implicated in the pathogenesis of PD. Experimentally, low Ca-Mg diets with or without added Al have been found to accelerate Al deposition in the CNS of rats and monkeys. Although excessive deposition of Mn produces similar neurotoxic action to Al in CNS tissues, the mechanism of Mn deposition coupled with Al loading in the presence of low Ca-Mg intake is not yet known. In this study, the deposition and metal-metal interaction of both Al and Mn in the CNS, visceral organs and bones of rats fed unbalanced mineral diets were analyzed. Male Wistar rats, weighing 200 g, were maintained for 90 days on the following diets: (Al standard diet, (B) low Ca diet, (C) low Ca-Mg diet, (D) low Ca-Mg diet with high Al. Al and Mn content were determined in the frontal cortex, spinal cord, kidney, muscle, abdominal aorta, femur and lumbar spine using neutron activation analysis (NAA). Our results demonstrate that serum Ca levels were decreased in the following dietary order: C 10%) weight change over one year in a representative sample of the US population which participated in the 1989 National Health Interview Survey (NHIS). Across all ages, a larger proportion of women than men reported both weight loss as well as weight gain of any amount (18.9% vs. 16.1% for weight loss and 20.0% vs. 16.1% for weight gain). In sex-specific logistic regression analyses, significant risk factors common to both sexes for substantial weight loss included divorced/separated marital status, smoking, increased number of blood pressure checks, increased BMI (body mass index) and increased number of bed days. Black race reduced the risk of weight loss for both men and women. Sex-specific risk factors for weight loss in men only were widowhood or never married marital status,while increasing age was a protective factor in women only. Concerning weight gain > 10% over the past year, increased number of blood pressure checks and having one or more diabetic parents were significant risk factors among both men and women; while never being married, increased age, BMI, and education exerted a protective effect in both sexes. For women only, risk factors for weight gain included black race, increased number of contacts with a health professional, and being unemployed. Intention to lose weight was associated with both weight gain and weight loss in both sexes, although it did not serve as a confounder in any of these relationships. A greater likelihood of substantial weight loss among women relative to men was diminished for persons with higher BMI, higher number of blood pressure checks, being widowed, divorced or separated, and intention to lose weight, A greater likelihood of substantial weight gain among women relative to men was diminished for persons with low BMI. The results of this cross-sectional study of weight change,involving a one year follow-up period, generally correspond with the results obtained by longitudinal studies involving a longer follow-up. C1 NIDDKD,BETHESDA,MD 20892. RP MELTZER, AA (reprint author), SOCIAL SCI SYST INC,7101 WISCONSIN AVE,SUITE 1300,BETHESDA,MD 20814, USA. FU NIDDK NIH HHS [N01-DK-1-2282] NR 26 TC 15 Z9 15 U1 0 U2 1 PU NORTH AMER ASSOC STUDY OBESITY PI BATON ROUGE PA 6400 PERKINS RD, BATON ROUGE, LA 70808 SN 1071-7323 J9 OBES RES JI Obes. Res. PD SEP PY 1995 VL 3 SU 2 BP S123 EP S134 PG 12 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA RZ535 UT WOS:A1995RZ53500007 PM 8581768 ER PT J AU SICHIERI, R RECINE, E EVERHART, JE AF SICHIERI, R RECINE, E EVERHART, JE TI GROWTH AND BODY-MASS INDEX OF BRAZILIANS AGES 9 THROUGH 17 YEARS SO OBESITY RESEARCH LA English DT Article; Proceedings Paper CT Workshop on Prevention of Obesity - Populations at Risk, Etiologic Factors and Intervention Strategies CY SEP 22-24, 1993 CL BALTIMORE, MD SP US Japan Cooperat Med Sci Program, US Japan Maltnutr Panel, NIDDKD, Div Digest Dis & Nutr, Obes Eating Disorders & Energy Regulat Progr, am, NIDDKD, Off Res Minor Hlth, NCI, NHLBI, NIA, NICHHD, Ctr Dis Control & Prevent, Indian Hlth Serv, Int Life Sci Inst DE SURVEY; OBESITY; RACE; INCOME; ADOLESCENCE ID CHILDREN; OBESITY AB Obesity during adolescence is considered a strong predictor of adult obesity, and obesity and overweight have been increasing among Brazilian adults, To gauge the relative frequency of overweight among adolescents in Brazil,we compared the distributions of body mass index (kg/m(2)) and stature in national population based samples of the U.S. and Brazil. U.S. adolescents were on average about 10 cm taller than Brazilians, although growth spurts occurred at the same age for both populations. Brazilian adolescents were leaner than their U.S. counterparts, This difference was reduced among girls in the postpubertal period, At age 17 years, U.S. boys were about 10 kg heavier than Brazilian boys, but the difference among girls was only 2 kg, In families above the poverty level in the more develop ed South region, body mass index distribution for boys was closer to that of the U.S., and older girls tended to have higher body mass index than U.S. girls, Within Brazil, body mass index varied by ethnicity with Mulattos, but not Blacks, of both sexes having lower body mass index than Whites of the same age, Urban adolescents had higher body mass index than those living in rural areas, In general, the patterns seen among Brazilian adults were found among children, Among girls, in particular, overweight has become an identifiable problem during adolescence. C1 UNIV ESTADUAL RIO JANEIRO,INST SOCIAL MED,BR-20550012 RIO JANEIRO,BRAZIL. UNIV BRASILIA,DEPT NUTR,BR-70910 BRASILIA,DF,BRAZIL. NIDDKD,BETHESDA,MD 20892. NR 17 TC 14 Z9 16 U1 0 U2 1 PU NORTH AMER ASSOC STUDY OBESITY PI BATON ROUGE PA 6400 PERKINS RD, BATON ROUGE, LA 70808 SN 1071-7323 J9 OBES RES JI Obes. Res. PD SEP PY 1995 VL 3 SU 2 BP S117 EP S121 PG 5 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA RZ535 UT WOS:A1995RZ53500006 PM 8581767 ER PT J AU RICE, LW MARK, SD BERKOWITZ, RS GOFF, BA LAGE, JM AF RICE, LW MARK, SD BERKOWITZ, RS GOFF, BA LAGE, JM TI CLINICOPATHOLOGICAL VARIABLES, OPERATIVE CHARACTERISTICS, AND DNA-PLOIDY IN PREDICTING OUTCOME IN OVARIAN EPITHELIAL CARCINOMA SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID FLOW CYTOMETRIC ANALYSIS; PROGNOSTIC FACTORS; CANCER; TUMORS; SURVIVAL; STAGE; PARAMETERS AB Objective: To test the hypothesis that DNA content can predict operative morbidity and survival in patients with ovarian carcinoma. Methods: Subjects included patients diagnosed with invasive epithelial ovarian carcinoma at Brigham and Women's Hospital between July 1987 and November 1989. Fifty-nine patients were included in this analysis, In all cases, now cytometry was performed on fresh tissue to evaluate DNA content. The medical records were reviewed in all patients for estimated blood loss, hospitalization days, intensive care unit days, operating room time, presence and size of residual disease, grade and type of tumor, stage, size of primary tumor, lymph node status, disease status, date of last examination, and number of months of follow-up. Results: Predictors for death included increasing age (P = .01), advanced stage (P = .007), the presence of malignant ascites (P = .03), residual tumor at completion of operation (P < .001), increased estimated blood loss (P < .001), increased hospitalization days (P < .001), and increased operating room hours (P < .001). When we controlled for age and stage, only estimated blood loss and residual tumor predicted poor outcome. Deoxyribonucleic acid ploidy, whether stratified as diploid or aneuploid or with DNA index cutoffs, did not predict tumor recurrence or survival rates. Conclusion: Deoxyribonucleic acid ploidy has not yet been proven to be of independent prognostic importance for identifying groups of patients at high risk of dying from invasive epithelial ovarian carcinoma. C1 BRIGHAM & WOMENS HOSP,DEPT OBSTET,DIV GYNECOL ONCOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT GYNECOL,DIV GYNECOL ONCOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT REPROD BIOL & PATHOL,DIV GYNECOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. NCI,DIV CANC ETIOL,BIOSTAT BRANCH,ROCKVILLE,MD. GEORGETOWN UNIV,SCH MED,DEPT PATHOL,WASHINGTON,DC. NR 21 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD SEP PY 1995 VL 86 IS 3 BP 379 EP 385 DI 10.1016/0029-7844(95)00163-L PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA RQ637 UT WOS:A1995RQ63700012 PM 7651646 ER PT J AU LAURIA, MR GONIK, B ROMERO, R AF LAURIA, MR GONIK, B ROMERO, R TI PULMONARY HYPOPLASIA - PATHOGENESIS, DIAGNOSIS, AND ANTENATAL PREDICTION SO OBSTETRICS AND GYNECOLOGY LA English DT Review ID FETAL BREATHING MOVEMENTS; CONGENITAL DIAPHRAGMATIC-HERNIA; UPPER RESPIRATORY-TRACT; RADIAL ALVEOLAR COUNT; LOW AMNIOTIC PRESSURE; LUNG DEVELOPMENT; PREMATURE RUPTURE; FLOW VELOCITY; OLIGOHYDRAMNIOS; MEMBRANES AB Objective: To review published data pertaining to the pathogenesis, antenatal prediction, and neonatal diagnosis of pulmonary hypoplasia. Data Sources: A computerized search of articles published through February 1995 was performed on the MEDLINE data base. Additional sources were identified through cross-referencing. Methods of Study Selection: All available references were reviewed initially by the authors, and their impact on the clinical significance of this condition was summarized. Data Extraction and Synthesis: Pulmonary hypoplasia can be understood best by first defining the embryology of lung development. Although pulmonary hypoplasia can occur as a primary event, most cases are secondary to congenital anomalies or pregnancy complications. Several methods have been proposed to predict the subsequent occurrence of pulmonary hypoplasia, but no single criterion has adequately confirmed sensitivity and specificity for clinical decision making. Conclusion: For patients with premature rupture of membranes, the gestational age at time of rupture carries the highest risk correlation with subsequent pulmonary hypoplasia. C1 WAYNE STATE UNIV,SCH MED,DEPT OBSTET & GYNECOL,DETROIT,MI 48201. NICHHD,PERINATOL RES BRANCH,BETHESDA,MD 20892. NR 76 TC 64 Z9 72 U1 0 U2 3 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD SEP PY 1995 VL 86 IS 3 BP 466 EP 475 DI 10.1016/0029-7844(95)00195-W PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA RQ637 UT WOS:A1995RQ63700030 PM 7651663 ER PT J AU KANG, DH ROTHMAN, N CHO, SH LIM, HS KWON, HJ KIM, SM SCHWARTZ, B STRICKLAND, PT AF KANG, DH ROTHMAN, N CHO, SH LIM, HS KWON, HJ KIM, SM SCHWARTZ, B STRICKLAND, PT TI ASSOCIATION OF EXPOSURE TO POLYCYCLIC AROMATIC-HYDROCARBONS (ESTIMATED FROM JOB CATEGORY) WITH CONCENTRATION OF 1-HYDROXYPYRENE GLUCURONIDE IN URINE FROM WORKERS AT A STEEL PLANT SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article DE POLYCYCLIC AROMATIC HYDROCARBONS; 1-HYDROXYPYRENE GLUCURONIDE; URINARY BIOMONITORING ID TAR PITCH VOLATILES; COKE-OVEN WORKERS; COAL-TAR; BIOLOGICAL INDICATOR; SKIN CONTAMINATION; FOUNDRY WORKERS; DIOL EPOXIDE; DNA ADDUCTS; EXCRETION; BENZO(A)PYRENE AB Objectives-increased risk of lung cancer has been associated with employment in the steel industry. This association is thought to be due in part to increased concentrations of polycyclic aromatic hydrocarbons (PAHs) in air found in this work environment. Measurement of PAH metabolites in human urine provides a means of assessing individual internal dose of PAHs. This study examined the relative contribution of occupation and smoking to urinary concentration of 1-hydroxypyrene glucuronide (1-OHPG) among a group of workers at a steel plant. Methods-Concentrations of 1-OHPG in urine from 44 workers with jobs associated with increased air concentrations of PAHs and 40 workers with jobs with low or no exposure to PAHs were measured. 20 workers in each group were not current smokers. Urinary 1-OHPG was measured by synchronous fluorescence spectroscopy after immunoaffinity chromatography specific for PAH metabolites. Results-Mean (SEM) urinary 1-OHPG concentration was 2.16 (0.42) pmol/ml urine among the 44 occupationally exposed workers compared with 0.38 (0.05) among the 40 workers with no or low exposure (P < 0.0001). Mean urinary 1-OHPG concentration was 1.82 (0.41) pmol/ml urine among the 44 current smokers compared with 0.75 (0.20) among the 40 non-smokers (P < 0.005). Mean 1-OHPG concentrations in nonsmokers were 0.26 (n = 20), 0.70 (n = 15), and 2.84 pmol/ml urine (n = 5) for strata of exposure to PANs (no or low, mid, and high) based on job category; the corresponding values in smokers were 0.55 (n = 20), 0.94 (n = 12), and 4.91 pmol/ml (n = 12), respectively. Multiple linear regression showed significant differences between subjects in different PAH exposure strata and between smokers and non-smokers. Both smoking and occupational exposure to PAHs were associated with increased concentrations of 1-OHPG in urine. Amounts of foods containing PAHs ingested by this group of workers were relatively low and did not contribute significantly to urinary 1-OHPG concentrations. Conclusions-These results indicate that 1-OHPG is a common urinary metabolite hr people with recent occupational exposure to PANs and is associated with both job category and estimated stratum of PAN exposure. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT ENVIRONM HLTH SCI,DIV OCCUPAT HLTH,BALTIMORE,MD. NCI,OCCUPAT STUDIES SECT,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD. SEOUL NATL UNIV,DEPT PREVENT MED,SEOUL,SOUTH KOREA. DONGGUK UNIV,DEPT PREVENT MED,POHANG,SOUTH KOREA. RI Kang, Dae Hee/E-8631-2012; OI Lim, Hyun-Sul/0000-0001-9972-2561 FU NIEHS NIH HHS [P01-ES06052, P30-ES03819] NR 29 TC 45 Z9 47 U1 0 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 SEP PY 1995 VL 52 IS 9 BP 593 EP 599 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RT544 UT WOS:A1995RT54400008 PM 7550799 ER PT J AU Yeudall, WA Jakus, J AF Yeudall, WA Jakus, J TI Cyclin kinase inhibitors add a new dimension to cell cycle control SO ORAL ONCOLOGY-EUROPEAN JOURNAL OF CANCER PART B LA English DT Review ID GROWTH-FACTOR; RETINOBLASTOMA PROTEIN; P53; CANCER; GENE; PHOSPHORYLATION; SUPPRESSION; ASSOCIATION; EXPRESSION; ONCOGENE RP Yeudall, WA (reprint author), NIDR,CELLULAR DEV & ONCOL LAB,MOLEC CARCINOGENESIS GRP,BETHESDA,MD 20892, USA. NR 101 TC 5 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0964-1955 J9 ORAL ONCOL JI Oral Oncol.-Eur. J. Cancer Pt. B PD SEP PY 1995 VL 31B IS 5 BP 291 EP 298 PG 8 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA TP100 UT WOS:A1995TP10000002 ER PT J AU SARAIVA, EMB PIMENTA, PFP BRODIN, TN ROWTON, E MODI, GB SACKS, DL AF SARAIVA, EMB PIMENTA, PFP BRODIN, TN ROWTON, E MODI, GB SACKS, DL TI CHANGES IN LIPOPHOSPHOGLYCAN AND GENE-EXPRESSION ASSOCIATED WITH THE DEVELOPMENT OF LEISHMANIA-MAJOR IN PHLEBOTOMUS-PAPATASI SO PARASITOLOGY LA English DT Article DE LEISHMANIA; SAND FLY; METACYCLIC; LIPOPHOSPHOGLYCAN ID SURFACE LIPOPHOSPHOGLYCAN; PROMASTIGOTES; STAGE; METACYCLOGENESIS; TRANSMISSION; PSYCHODIDAE; DIPTERA AB Stage-specific molecular and morphogenic markers were used to follow the kinetics of appearance, number, and position of metacyclic promastigotes developing during the course of L. major infection in a natural vector, Phlebotomzrs papatasi. Expression of surface lipophosphoglycan (LPG) on transformed promastigotes was delayed until the appearance of nectomonad forms on day 3, and continued to be abundantly expressed by all promastigotes thereafter. An epitope associate with arabinose substitution of LPG side-chain oligosaccharides, identified by its differential expression by metacyclics in vitro, was detected on the surface of a low proportion of midgut promastigotes beginning on day 5, and on up to 60% of promatigotes on days 10 and 15. In contrast 100% of the parasites egested from the mouthparts during forced feeding of 15 day infected flies stained strongly for this epitope. At each time-point, the surface expression of the modified LPG was restricted to morphologically distinguished metacyclic forms. Ultrastructural study of the metacyclic surface revealed an approximate 2-fold increase in the thickness of the surface coat compared to nectomonad forms, suggesting elongation of LPG as occurs during metacyclogenesis in vitro. A metacyclic-associated transcript (MAT-1), another marker identified by its differential expression in vitro, also showed selective expression by promastigotes in the fly, and was used in in situ hybridization studies to demonstrate the positioning of metacyclics in the anterior gut. C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. WALTER REED ARMY INST RES,DEPT ENTOMOL,WASHINGTON,DC 20307. RI Rowton, Edgar/A-4474-2012; Rowton, Edgar/A-1975-2011 OI Rowton, Edgar/0000-0002-1979-1485 NR 26 TC 56 Z9 57 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0031-1820 J9 PARASITOLOGY JI Parasitology PD SEP PY 1995 VL 111 BP 275 EP 287 PN 3 PG 13 WC Parasitology SC Parasitology GA RV202 UT WOS:A1995RV20200004 PM 7567096 ER PT J AU MALLOY, MH HOFFMAN, HJ AF MALLOY, MH HOFFMAN, HJ TI PREMATURITY, SUDDEN-INFANT-DEATH-SYNDROME, AND AGE OF DEATH SO PEDIATRICS LA English DT Article ID BIRTH-WEIGHT; RISK-FACTORS; EPIDEMIOLOGY AB Objective, To determine if preterm infants are at greater risk for sudden infant death syndrome (SIDS) than term infants and to determine if the postconceptional age of SIDS deaths varies by gestational age at birth. Methods. A cohort analysis was conducted using data from the 1987 United States' Birth Cohort Linked Birth/Infant Death Certificate tapes. SIDS was defined as the death of any infant who was >24 weeks gestation at birth; weighed >500 g at birth; was assigned an international Classification of Disease-9th Revision (ICD-9) underlying cause of death of 7980; and had an autopsy. Results. The overall SIDS rate using our definition was 1.20 deaths/1000 live births. The SIDS rates by gestational age categories of 24 to 28 weeks, 29 to 32 weeks, 33 to 36 weeks, and 37 or more weeks were 3.55 3.01, 2.27, and 1.06 deaths/1000 live births, respectively. Because of misclassification of gestational age among the most preterm infants, a restricted analysis was conducted on SIDS victims whose gestational ages fell within cutoff values derived from a methodology that excluded gestational. age assessments assumed to be invalid. This subgroup analysis showed a mean (standard deviates) postconceptional age of death for SIDS for infants of 24 to 28 weeks, 29 to 32 weeks, and 33 to 36 weeks gestation to be 45.8 (8.3), 47.3 (8.6), and 48.0 (8.3) weeks, respectively, compared with 52.3 (8.5) weeks for term infants (ANOVA P=.0001). Conclusions. We infer from this analysis that preterm infants are at higher risk for SIDS than term infants, and that the postconceptional age of peak vulnerability for SIDS may differ by 4 to 6 weeks between preterm and term infants. C1 NIDCD,EPIDEMIOL STAT & DATA SYST BRANCH,BETHESDA,MD. RP MALLOY, MH (reprint author), UNIV TEXAS,MED BRANCH,DEPT PEDIAT,GALVESTON,TX 77555, USA. FU NHLBI NIH HHS [R03-HL48932-01] NR 34 TC 92 Z9 95 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 1995 VL 96 IS 3 BP 464 EP 471 PN 1 PG 8 WC Pediatrics SC Pediatrics GA RT954 UT WOS:A1995RT95400010 PM 7651779 ER PT J AU KLEIN, DL AF KLEIN, DL TI MULTICENTER ACELLULAR PERTUSSIS-VACCINE TRIAL - A NATIONAL-INSTITUTES-OF-HEALTH PERSPECTIVE SO PEDIATRICS LA English DT Editorial Material RP KLEIN, DL (reprint author), NIAID,DIV MICROBIOL & INFECT DIS,RESP DIS BRANCH,SOLAR BLDG,ROOM 3B03,BETHESDA,MD 20892, USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 1995 VL 96 IS 3 SU S BP 547 EP 548 PG 2 WC Pediatrics SC Pediatrics GA RU712 UT WOS:A1995RU71200001 PM 7659474 ER PT J AU EDWARDS, KM MEADE, BD DECKER, MD REED, GF RENNELS, MB STEINHOFF, MC ANDERSON, EL ENGLUND, JA PICHICHERO, ME DELORIA, MA DEFOREST, A AF EDWARDS, KM MEADE, BD DECKER, MD REED, GF RENNELS, MB STEINHOFF, MC ANDERSON, EL ENGLUND, JA PICHICHERO, ME DELORIA, MA DEFOREST, A TI COMPARISON OF 13 ACELLULAR PERTUSSIS VACCINES - OVERVIEW AND SEROLOGIC RESPONSE SO PEDIATRICS LA English DT Article; Proceedings Paper CT Meeting of the Society-for-Pediatric-Research CY MAY 06, 1992 CL BALTIMORE, MD SP Soc Pediat Res ID DIPHTHERIA-TETANUS-PERTUSSIS; BORDETELLA-PERTUSSIS; FILAMENTOUS HEMAGGLUTININ; ANTIBODY-RESPONSE; TOXIN; EFFICACY; CELLS; MICE; INFECTION; ANTITOXIN AB Objective. To compare the immunogenicity of a licensed conventional whole-cell (WCL) and 13 diphtheria-tetanus-acellular pertussis (DTaP) vaccines that differed in source, method of manufacture, and included antigens; all vaccines included diphtheria and tetanus toxoids. Methods. Healthy infants were enrolled through six university-based vaccine and treatment evaluation units and were randomized to receive one of the study vaccines at 2, 4, and 6 months of age. Sera were obtained before the first immunization and 1 month after the third immunization and were analyzed for antibody to pertussis toxin (PT), filamentous hemagglutinin, fimbriae, pertactin, and diphtheria and tetanus toxins. Chinese hamster ovary cell toxin neutralization assays were performed, and levels of agglutinating antibodies were determined. Results. Of 2342 infants enrolled, 1942 contributed usable preimmunization and postimmunization serum specimens. Each vaccine produced significant increases in antibodies directed against the included antigens; postimmunization antibody titers differed significantly among the DTaP vaccines. For each evaluated antigen, the majority of DTaP vaccines produced antibody responses that equaled or exceeded those produced by WCL. For some antigens (eg, PT), mean antibody levels by vaccine correlated poorly with the quantity of antigen included in each vaccine; for others (eg, fimbriae), there was a close correlation. Conclusion. Although serologic correlates of pertussis immunity are not defined, it is clear that DTaP vaccines can stimulate immune responses that exceed those of licensed whole-cell vaccine with respect to the measured antibodies. Particularly for PT, immunogenicity seems to depend on factors in addition to antigen concentration, possibly including antigen derivation and formulation. No DTaP was most or least immunogenic with respect to all included antigens. C1 VANDERBILT UNIV,SCH MED,DEPT PREVENT MED,NASHVILLE,TN 37212. VANDERBILT UNIV,SCH MED,DEPT MED,NASHVILLE,TN 37212. US FDA,CTR DRUG EVALUAT & RES,DEPT PEDIAT,ROCKVILLE,MD 20857. US FDA,CTR DRUG EVALUAT & RES,DIV BACTERIAL PROD,ROCKVILLE,MD 20857. NIAID,DIV MICROBIOL & INFECT DIS,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,CTR VACCINE DEV,BALTIMORE,MD 21201. JOHNS HOPKINS UNIV,DEPT PEDIAT,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,DEPT INT HLTH,BALTIMORE,MD 21218. BAYLOR COLL MED,DEPT MICROBIOL & IMMUNOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. ST LOUIS UNIV,SCH MED,DEPT MED,ST LOUIS,MO 63104. UNIV ROCHESTER,SCH MED & DENT,DEPT PEDIAT,ROCHESTER,NY 14642. TEMPLE UNIV,SCH MED,DEPT MICROBIOL,PHILADELPHIA,PA 19122. TEMPLE UNIV,SCH MED,DEPT PEDIAT,PHILADELPHIA,PA 19122. ST CHRISTOPHERS HOSP CHILDREN,PHILADELPHIA,PA 19133. FU NIAID NIH HHS [N01-AI72629, N01-AI25135, N01-AI62515] NR 37 TC 205 Z9 210 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 SEP PY 1995 VL 96 IS 3 SU S BP 548 EP 557 PG 10 WC Pediatrics SC Pediatrics GA RU712 UT WOS:A1995RU71200002 PM 7659475 ER PT J AU DECKER, MD EDWARDS, KM STEINHOFF, MC RENNELS, MB PICHICHERO, ME ENGLUND, JA ANDERSON, EL DELORIA, MA REED, GF AF DECKER, MD EDWARDS, KM STEINHOFF, MC RENNELS, MB PICHICHERO, ME ENGLUND, JA ANDERSON, EL DELORIA, MA REED, GF TI COMPARISON OF 13 ACELLULAR PERTUSSIS VACCINES - ADVERSE REACTIONS SO PEDIATRICS LA English DT Article; Proceedings Paper CT Meeting of the Society-for-Pediatric-Research CY MAY 06, 1992 CL BALTIMORE, MD SP Soc Pediat Res ID UNITED-STATES; TETANUS TOXOIDS; CHILDREN; DIPHTHERIA; INFANTS; IMMUNOGENICITY; IMMUNIZATION; SAFETY; SEIZURES; BOOSTER AB Objective. To compare the reactogenicity of a licensed conventional whole-cell (WCL) and 13 acellular pertussis vaccines that differed in the source, manufacture, and quantity of included antigens; all vaccines included diphtheria and tetanus toxoids. Methods. Healthy infants were enrolled through six university-based vaccine and treatment evaluation units and were randomized to receive one of the study vaccines at 2, 4, and 6 months of age. Parents recorded the occurrence of fever, redness, swelling, pain, fussiness, drowsiness, anorexia, and use of antipyretics for 2 weeks after each inoculation; nurses interviewed parents on the third day and at each succeeding visit; long-term follow-up information was collected from parents and medical records 1 year after the third immunization. Results. Of 2200 vaccinated infants, 2189 contributed reaction data after 6375 vaccinations. For every acellular vaccine, every monitored reaction except vomiting occurred at a significantly lower frequency and severity than was seen with WCL. The groups receiving acellular pertussis vaccines differed significantly with respect to redness, swelling, pain, and vomiting, but not with respect to fussiness, antipyretic use, drowsiness, or anorexia. C1 VANDERBILT UNIV,SCH MED,DEPT MED INFECT DIS,NASHVILLE,TN 37232. VANDERBILT UNIV,SCH MED,DEPT PEDIAT,NASHVILLE,TN 37232. JOHNS HOPKINS UNIV,DEPT PEDIAT,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,DEPT INT HLTH,BALTIMORE,MD 21218. UNIV MARYLAND,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,CTR VACCINE DEV,BALTIMORE,MD 21201. UNIV ROCHESTER,SCH MED,DEPT PEDIAT,ROCHESTER,NY 14642. BAYLOR COLL MED,DEPT MICROBIOL & IMMUNOL,DEPT PEDIAT,HOUSTON,TX 77030. ST LOUIS UNIV,SCH MED,DEPT MED,ST LOUIS,MO 63104. NIAID,DIV MICROBIOL & INFECT DIS,BETHESDA,MD 20892. RP DECKER, MD (reprint author), VANDERBILT UNIV,MED CTR N A1116,SCH MED,DEPT PREVENT MED,NASHVILLE,TN 37232, USA. FU NIAID NIH HHS [N01-AI25135, N01-AI62515, N01-AI72629] NR 48 TC 177 Z9 185 U1 2 U2 5 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 SEP PY 1995 VL 96 IS 3 SU S BP 557 EP 566 PG 10 WC Pediatrics SC Pediatrics GA RU712 UT WOS:A1995RU71200003 PM 7659476 ER PT J AU STEINHOFF, MC REED, GF DECKER, MD EDWARDS, KM ENGLUND, JA PICHICHERO, ME RENNELS, MB ANDERSON, EL DELORIA, MA MEADE, BD AF STEINHOFF, MC REED, GF DECKER, MD EDWARDS, KM ENGLUND, JA PICHICHERO, ME RENNELS, MB ANDERSON, EL DELORIA, MA MEADE, BD TI RANDOMIZED COMPARISON OF REACTOGENICITY AND IMMUNOGENICITY OF 2 WHOLE-CELL PERTUSSIS VACCINES SO PEDIATRICS LA English DT Article; Proceedings Paper CT Meeting of the Society-for-Pediatric-Research CY MAY 06, 1992 CL BALTIMORE, MD SP Soc Pediat Res ID ANTIBODY-RESPONSE; ADVERSE REACTIONS; DIPHTHERIA; ANTIGENS; DTP AB Objective. To compare prospectively the reactogenicity and immunogenicity of two licensed whole-cell pertussis vaccines. Methods. We conducted a prospective, randomized, double-blinded assessment of two licensed whole-cell pertussis vaccines with diphtheria and tetanus toxoids that were included in a multicenter trial evaluating 13 acellular pertussis vaccines. Infants were immunized at 2, 4, and 6 months of age with a single lot of Lederle (309 infants) or Massachusetts Public Health Biologic Laboratories (MPHBL; 94 infants) vaccine. Results. The group receiving the Lederle vaccine demonstrated significantly higher antibody titers to pertussis toxin by enzyme-linked immunosorbent assay (ELISA) and by the Chinese hamster ovary cell pertussis toxin neutralization assay, and to fimbrial antigens by ELISA, as well as higher mean agglutinin titers. In contrast, the group receiving the MPHBL vaccine demonstrated higher ELISA antibody levels to filamentous hemagglutinin and pertactin. Similar differences were observed in the proportions of vaccinees seroconverting to these antigens. Rates of systemic and local reactions were relatively low for both vaccines. Although the Lederle product had substantially lower reactogenicity in this study than previously reported for that vaccine, the MPHBL vaccine was significantly less reactogenic in nearly all clinical categories. Conclusion. The two whole-cell vaccines demonstrated statistically significant differences in postimmunization antibody levels to all six evaluated pertussis antigens. Whether these statistically significant differences in antibody levels have clinical relevance is not clear. Rates of nearly all local and systemic reactions were significantly lower among the MPHBL group than the Lederle group. Licensed whole-cell diphtheria-tetanus-pertussis vaccines produced by different manufacturers cannot be assumed to be similar in reactogenicity or immunogenicity. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. NIAID,DIV MICROBIOL & INFECT DIS,BETHESDA,MD 20892. VANDERBILT UNIV,SCH MED,DEPT PREVENT MED,NASHVILLE,TN 37212. VANDERBILT UNIV,SCH MED,DEPT MED INFECT DIS,NASHVILLE,TN 37212. VANDERBILT UNIV,SCH MED,DEPT PEDIAT,NASHVILLE,TN 37212. BAYLOR COLL MED,DEPT MICROBIOL & IMMUNOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. UNIV ROCHESTER,SCH MED,DEPT PEDIAT,ROCHESTER,NY 14642. UNIV MARYLAND,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,CTR VACCINE DEV,BALTIMORE,MD 21201. ST LOUIS UNIV,SCH MED,DEPT MED,ST LOUIS,MO 63104. US FDA,CTR DRUG EVALUAT & RES,DIV BACTERIAL PROD,ROCKVILLE,MD 20857. RP STEINHOFF, MC (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT INT HLTH,624 N BROADWAY,ROOM 125,BALTIMORE,MD 21205, USA. FU NIAID NIH HHS [N01 AI62515, N01 AI25135, N01 AI72629] NR 14 TC 21 Z9 21 U1 1 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 1995 VL 96 IS 3 SU S BP 567 EP 570 PG 4 WC Pediatrics SC Pediatrics GA RU712 UT WOS:A1995RU71200004 PM 7659477 ER PT J AU MEADE, BD DEFOREST, A EDWARDS, KM ROMANI, TA LYNN, F OBRIEN, CH SWARTZ, CB REED, GF DELORIA, MA AF MEADE, BD DEFOREST, A EDWARDS, KM ROMANI, TA LYNN, F OBRIEN, CH SWARTZ, CB REED, GF DELORIA, MA TI DESCRIPTION AND EVALUATION OF SEROLOGIC ASSAYS USED IN A MULTICENTER TRIAL OF ACELLULAR PERTUSSIS VACCINES SO PEDIATRICS LA English DT Article; Proceedings Paper CT Meeting of the Society-for-Pediatric-Research CY MAY 06, 1992 CL BALTIMORE, MD SP Soc Pediat Res ID MONOCLONAL-ANTIBODIES; BORDETELLA-PERTUSSIS; TOXIN AB Objective. To describe and evaluate the assays used to measure the antibody responses in infants to 13 experimental acellular pertussis vaccines and 2 licensed whole-cell pertussis vaccines. Methods. During a 53-week period, preimmunization and postimmunization sera were assayed for immunoglobulin G antibodies to pertussis toxin, filamentous hemagglutinin, pertactin, and a mixture of type 2 and type 3 fimbriae by enzyme-linked immunosorbent assay (ELISA), for whole-cell agglutinins (AGG), and for pertussis toxin-neutralizing antibodies by the Chinese hamster ovary cell assay. All ELISA reagents were characterized to assure antigen and isotype specificity of the assays. Intralaboratory reproducibility and temporal stability were evaluated by analysis of results of control sera and by assessment of the response to the control whole-cell vaccine. Interlaboratory reproducibility was assessed by repeating the assays on preimmunization and postimmunization sera for 10% of the infants in a second laboratory. Results. For control sera having antibody concentrations at least four times the minimum level of detection, the coefficients of variation within and between the ELISAs consistently were less than 20%. Trend analysis indicated that none of the assays drifted by more than 20% during the study period, and no significant drift was seen in the response to the control whole-cell vaccine. Results from the two laboratories correlated well; correlation coefficients were .93 or greater for the four ELISAs, .79 for the Chinese hamster ovary cell assay, and .82 for the AGG assay. For four of the six assays, there was either no difference or a modest (< 15%) difference in the geometric mean values for sera tested in both laboratories. Larger quantitative differences were observed for the AGG (45% difference) and pertactin (61% difference) assays. Conclusion. Assay reproducibility and stability indicate that the standardized methods can be transferred between laboratories, and that the results accrued during a 1-year period for the 15 vaccines can be compared. C1 TEMPLE UNIV,SCH MED,DEPT MICROBIOL,PHILADELPHIA,PA 19122. TEMPLE UNIV,SCH MED,DEPT PEDIAT,PHILADELPHIA,PA 19122. ST CHRISTOPHERS HOSP CHILDREN,PHILADELPHIA,PA 19133. VANDERBILT UNIV,SCH MED,DEPT PEDIAT,NASHVILLE,TN 37212. NIAID,DIV MICROBIOL & INFECT DIS,BETHESDA,MD 20892. RP MEADE, BD (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,MAIL CODE HFM 490,ROCKVILLE,MD 20852, USA. FU NIAID NIH HHS [N01 AI72629, N01 AI25135, N01 AI62515] NR 10 TC 87 Z9 89 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 1995 VL 96 IS 3 SU S BP 570 EP 575 PG 6 WC Pediatrics SC Pediatrics GA RU712 UT WOS:A1995RU71200005 PM 7659478 ER PT J AU RENNELS, MB REED, GF DECKER, MD EDWARDS, KM PICHICHERO, ME DELORIA, MA ENGLUND, JA ANDERSON, EL STEINHOFF, MC DEFOREST, A MEADE, BD AF RENNELS, MB REED, GF DECKER, MD EDWARDS, KM PICHICHERO, ME DELORIA, MA ENGLUND, JA ANDERSON, EL STEINHOFF, MC DEFOREST, A MEADE, BD TI SIMULTANEOUS ADMINISTRATION OF HAEMOPHILUS-INFLUENZAE TYPE-B VACCINE WITH ACELLULAR OR WHOLE-CELL PERTUSSIS-VACCINE - EFFECTS ON REACTOGENICITY AND IMMUNE-RESPONSES TO PERTUSSIS VACCINES SO PEDIATRICS LA English DT Article; Proceedings Paper CT Meeting of the Society-for-Pediatric-Research CY MAY 06, 1992 CL BALTIMORE, MD SP Soc Pediat Res ID PROTEIN CONJUGATE VACCINE; YOUNG INFANTS; DIPHTHERIA; TETANUS; SAFETY; IMMUNOGENICITY; SYRINGE AB Objective. To evaluate the effect of simultaneous Haemophilus influenzae type b conjugate (Hib) vaccination on the safety and immunogenicity of selected acellular (DTaP) and whole-cell (DTP) pertussis vaccines with diphtheria and tetanus toxoids combined. Methods. Enrollment of infants into a large multicenter study of the safety and immunogenicity of 13 DTaP and 2 DTP vaccines was partially completed when the first Hib vaccine, HbOC (Haemophilus b oligosaccharide conjugate vaccine), was licensed for use in infants. Thereafter, at each immunization most infants received HbOC simultaneously with DTaP (or DTP), administered in opposite thighs. Postvaccination geometric mean titers or concentrations (GMTs) of pertussis antibodies as measured by six different assays were compared pairwise among groups of infants receiving 0, 1, 2, or 3 simultaneous HbOC immunizations. The incidence of reactions was compared between infants who received only DTaP or DTP and those who received HbOC simultaneously. Results. Comparison of postvaccination GMTs was possible among groups of infants receiving different numbers of simultaneous immunizations for 10 of the 13 DTaP and both DTP vaccines. Increased HbOC exposure had no consistent dose-response effect on antibody titers for DTaP or DTP vaccines in any assay. Significant differences between groups in postvaccination GMTs were observed with 4 DTaP vaccines in 1 to 2 assays each; the GMTs were higher with increasing HbOC exposure for 2 DTaP vaccines and lower for 2 others. There was no significant increase in reactions with simultaneous HbOC and DTaP immunization. Conclusions. Based on these retrospective analyses, there did not seem to be an interference in pertussis immunogenicity or alteration in reactogenicity associated with the simultaneous administration of HbOC and DTaP. These findings are encouraging with respect to the development of DTaP-Hib combination vaccines. C1 UNIV MARYLAND,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,CTR VACCINE DEV,BALTIMORE,MD 21201. NIAID,DIV MICROBIOL & INFECT DIS,BETHESDA,MD 20892. VANDERBILT UNIV,SCH MED,DEPT PREVENT MED,NASHVILLE,TN 37212. VANDERBILT UNIV,SCH MED,DEPT MED,NASHVILLE,TN 37212. VANDERBILT UNIV,SCH MED,DEPT PEDIAT,NASHVILLE,TN 37212. UNIV ROCHESTER,SCH MED,DEPT PEDIAT,ROCHESTER,NY. BAYLOR COLL MED,DEPT MICROBIOL & IMMUNOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. ST LOUIS UNIV,DEPT MED,ST LOUIS,MO 63103. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT INT HLTH,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH PUBL HLTH,BALTIMORE,MD. ST CHRISTOPHERS HOSP CHILDREN,PHILADELPHIA,PA 19133. TEMPLE UNIV,SCH MED,DEPT MICROBIOL,PHILADELPHIA,PA 19122. TEMPLE UNIV,SCH MED,DEPT PEDIAT,PHILADELPHIA,PA 19122. US FDA,ROCKVILLE,MD 20857. FU NIAID NIH HHS [N01-AI62515, N01-AI72629, N01-AI25135] NR 15 TC 7 Z9 7 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 1995 VL 96 IS 3 SU S BP 576 EP 579 PG 4 WC Pediatrics SC Pediatrics GA RU712 UT WOS:A1995RU71200006 PM 7659479 ER PT J AU ENGLUND, JA ANDERSON, EL REED, GF DECKER, MD EDWARDS, KM PICHICHERO, ME STEINHOFF, MC RENNELS, MB DEFOREST, A MEADE, BD AF ENGLUND, JA ANDERSON, EL REED, GF DECKER, MD EDWARDS, KM PICHICHERO, ME STEINHOFF, MC RENNELS, MB DEFOREST, A MEADE, BD TI THE EFFECT OF MATERNAL ANTIBODY ON THE SEROLOGIC RESPONSE AND THE INCIDENCE OF ADVERSE REACTIONS AFTER PRIMARY IMMUNIZATION WITH ACELLULAR AND WHOLE-CELL PERTUSSIS VACCINES COMBINED WITH DIPHTHERIA AND TETANUS TOXOIDS SO PEDIATRICS LA English DT Article; Proceedings Paper CT Meeting of the Society-for-Pediatric-Research CY MAY 06, 1992 CL BALTIMORE, MD SP Soc Pediat Res ID BORDETELLA-PERTUSSIS; PASSIVE-IMMUNITY; INFANTS AB Objective. To evaluate the effect of maternally derived antibody on the immunogenicity and reactogenicity of acellular (DTaP) or whole-cell (DTP) pertussis vaccine with diphtheria and tetanus toxoids combined. Methods. A total of 2342 infants were randomized to receive one of 13 DTaP or 2 DTP vaccines at 2, 4, and 6 months of age. The correlation between preimmunization and postimmunization antibody after three doses of vaccine and the relation between preimmunization antibody and adverse reactions after the first immunization were modeled by linear regression. Results. After DTP but not DTaP, higher levels of preexisting antibody were associated with substantial (28% to 56%) reductions in the subsequent antibody response to pertussis toxin (PT). For other pertussis antibodies, modest inverse correlations were seen between preexisting antibody concentrations and most postimmunization antibody responses (resulting in 8% to 18% reductions in postimmunization antibody) for both DTP and DTaP. There was no consistent association in any DTP or DTaP group between adverse reactions and preimmunization antibody levels. Conclusion. The PT antibody response to DTaP, unlike DTP, is not adversely affected by preexisting antibody to PT. Inhibitory effects with respect to other antibodies, seen with both DTP and DTaP, were relatively modest. Our data suggest that the use of acellular pertussis vaccines in adults, which could confer higher levels of antibody in women before pregnancy, would be unlikely to adversely affect pertussis antibody responses after DTaP among infants born to mothers with high antibody levels. C1 BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. ST LOUIS UNIV,SCH MED,DEPT MED,ST LOUIS,MO 63104. NIAID,DIV MICROBIOL & INFECT DIS,BETHESDA,MD 20892. VANDERBILT UNIV,SCH MED,DEPT PREVENT MED,NASHVILLE,TN 37212. VANDERBILT UNIV,SCH MED,DEPT MED INFECT DIS,NASHVILLE,TN 37212. VANDERBILT UNIV,SCH MED,DEPT PEDIAT,NASHVILLE,TN 37212. UNIV ROCHESTER,SCH MED,DEPT PEDIAT,ROCHESTER,NY. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT INT HLTH,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH PUBL HLTH,BALTIMORE,MD 21205. UNIV MARYLAND,DEPT PEDIAT,BALTIMORE,MD 21201. TEMPLE UNIV,SCH MED,DEPT MICROBIOL,PHILADELPHIA,PA 19122. TEMPLE UNIV,SCH MED,DEPT PEDIAT,PHILADELPHIA,PA 19122. ST CHRISTOPHERS HOSP CHILDREN,PHILADELPHIA,PA 19133. US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,BETHESDA,MD 20892. RP ENGLUND, JA (reprint author), BAYLOR COLL MED,DEPT MICROBIOL & IMMUNOL,1 BAYLOR PLAZA,HOUSTON,TX 77030, USA. FU NIAID NIH HHS [N01-AI25135, N01-AI62515, N01-AI72629] NR 22 TC 113 Z9 118 U1 0 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 SEP PY 1995 VL 96 IS 3 SU S BP 580 EP 584 PG 5 WC Pediatrics SC Pediatrics GA RU712 UT WOS:A1995RU71200007 PM 7659480 ER PT J AU CHRISTY, C PICHICHERO, ME REED, GF DECKER, MD ANDERSON, EL RENNELS, MB ENGLUND, JA EDWARDS, KM STEINHOFF, MC AF CHRISTY, C PICHICHERO, ME REED, GF DECKER, MD ANDERSON, EL RENNELS, MB ENGLUND, JA EDWARDS, KM STEINHOFF, MC TI EFFECT OF GENDER, RACE, AND PARENTAL EDUCATION ON IMMUNOGENICITY AND REPORTED REACTOGENICITY OF ACELLULAR AND WHOLE-CELL PERTUSSIS VACCINES SO PEDIATRICS LA English DT Article AB Objective. To determine whether gender, race (black or white), or level of parental education influenced serologic responses or reporting of clinical reactions after immunization with acellular (DTaP) or whole-cell (DTP) pertussis vaccine with diphtheria and tetanus toxoids combined. Methods. Healthy infants were prospectively randomized to receive one of 13 DTaP, Lederle DTP, or another DTP. Parents recorded the occurrence of adverse reactions for 2 weeks after each inoculation. Sera obtained before the first immunization and 1 month after the third immunization were analyzed for antibody to pertussis toxin, filamentous hemagglutinin, fimbriae, and pertactin (PRN). Chinese hamster ovary cell pertussis toxin neutralization assays were performed, and levels of agglutinating antibodies determined. Results. Prevaccination antibody levels did not differ by race, gender, or parental education. Postimmunization geometric mean titers (GMTs) were strongly and consistently associated with race. For both DTaP and DTP and for every included antigen, postimmunization GMTs were about twice as high for black as for white infants. Among DTaP recipients, these differences were significant for pertussis toxin, Chinese hamster ovary cell pertussis toxin neutralization assay, filamentous hemagglutinin, PRN, and agglutinins; among the much smaller sample of WCL recipients, the differences achieved or approached statistical significance for agglutinins, PRN, and fimbriae. These findings were confirmed by regression analyses that controlled for gender, parental education, study site, and preimmunization antibody level. Reported reactions were not correlated with parental education level and showed no material correlation with gender. Black infants were reported to have had more pain than white infants after receiving WCL and DTaP and were reported to be more fussy after receiving WCL. Conclusions. The consistently higher postimmunization GMTs among black infants seems to be a real finding for which we have no explanation; the infants did not significantly differ by race in vaccine assignment, preimmunization antibody levels, age at immunization, or interval from immunization to phlebotomy. These observations should be confirmed and further evaluated in future pertussis vaccine trials. Reported differences by race in pain and fussiness after receiving WCL might reflect chance, differences by race in the occurrence of reactions, or differences by race in the reporting of reactions. C1 UNIV ROCHESTER,SCH MED,DEPT PEDIAT,ROCHESTER,NY. NIAID,DIV MICROBIOL & INFECT DIS,BETHESDA,MD 20892. VANDERBILT UNIV,SCH MED,DEPT PREVENT MED,NASHVILLE,TN 37212. VANDERBILT UNIV,SCH MED,DEPT MED,NASHVILLE,TN 37212. VANDERBILT UNIV,SCH MED,DEPT PEDIAT,NASHVILLE,TN 37212. ST LOUIS UNIV,SCH MED,DEPT MED,ST LOUIS,MO 63104. UNIV MARYLAND,SCH MED,CTR VACCINE DEV,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21201. BAYLOR COLL MED,DEPT MICROBIOL & IMMUNOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. JOHNS HOPKINS UNIV,DEPT PEDIAT,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,DEPT INT HLTH,BALTIMORE,MD 21218. FU NIAID NIH HHS [N01-AI62515, N01-AI72629, N01-AI25135] NR 15 TC 24 Z9 25 U1 0 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 SEP PY 1995 VL 96 IS 3 SU S BP 584 EP 587 PG 4 WC Pediatrics SC Pediatrics GA RU712 UT WOS:A1995RU71200008 PM 7659481 ER PT J AU DELORIA, MA BLACKWELDER, WC DECKER, MD ENGLUND, JA STEINHOFF, MC PICHICHERO, ME RENNELS, MB ANDERSON, EL EDWARDS, KM AF DELORIA, MA BLACKWELDER, WC DECKER, MD ENGLUND, JA STEINHOFF, MC PICHICHERO, ME RENNELS, MB ANDERSON, EL EDWARDS, KM TI ASSOCIATION OF REACTIONS AFTER CONSECUTIVE ACELLULAR OR WHOLE-CELL PERTUSSIS-VACCINE IMMUNIZATIONS SO PEDIATRICS LA English DT Article AB Objective. To evaluate the relative frequency of adverse reactions after initial and subsequent immunizations among infants receiving primary immunization with acellular (DTaP) or whole-cell (DTP) pertussis vaccine with diphtheria and tetanus combined. Methods. We examined the occurrence of common reactions in 2127 infants within 48 hours after immunization at 2, 4, and 6 months with one of 13 DTaP or with Lederle DTP (WCL). Data on at least two consecutive immunizations were available for 357 WCL recipients and 1770 DTaP recipients. For these analyses, reactions evaluated included fever of 100.4 degrees F (38 degrees C) or greater, redness of 21 mm or larger, swelling of 21 mm or larger, moderate or severe pain, moderate or severe fussiness, loss of appetite, drowsiness, and vomiting. Results. With one exception, reactions were approximately 1.5 to 8 times more likely to occur in WCL recipients if the same reaction had been observed at the previous immunization (the single exception was redness after the second immunization). Both initial and repeated reactions were less likely in DTaP than in WCL recipients. As with WCL recipients, risks of repeated reactions in DTaP recipients were higher than the risks of initial reactions (from 2.5 to 24 times as high). Conclusion. Reactions after a second or third immunization with either WCL or DTaP vaccine are more likely to occur in infants who had the same reaction after the preceding immunization. Absolute risks of repeated reactions tended to be lower after DTaP vaccine than after the WCL vaccine. C1 VANDERBILT UNIV,SCH MED,DEPT PREVENT MED,NASHVILLE,TN 37212. VANDERBILT UNIV,SCH MED,DEPT MED INFECT DIS,NASHVILLE,TN 37212. VANDERBILT UNIV,SCH MED,DEPT PEDIAT,NASHVILLE,TN 37212. BAYLOR COLL MED,DEPT MICROBIOL & IMMUNOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. JOHNS HOPKINS UNIV,DEPT PEDIAT,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,DEPT INT HLTH,BALTIMORE,MD 21218. UNIV ROCHESTER,SCH MED,DEPT PEDIAT,ROCHESTER,NY. UNIV MARYLAND,SCH MED,CTR VACCINE DEV,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21201. ST LOUIS UNIV,SCH MED,DEPT MED,ST LOUIS,MO 63104. RP DELORIA, MA (reprint author), NIAID,DIV MICROBIOL & INFECT DIS,BIOMETRY BRANCH,SOLAR BLDG,ROOM 3A-41,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [N01-AI25135, N01-AI62515, N01-AI72629] NR 7 TC 31 Z9 35 U1 0 U2 4 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 SEP PY 1995 VL 96 IS 3 SU S BP 592 EP 594 PG 3 WC Pediatrics SC Pediatrics GA RU712 UT WOS:A1995RU71200010 PM 7659483 ER PT J AU MEADE, BD LYNN, F REED, GF MINK, CM ROMANI, TA DEFOREST, A DELORIA, MA AF MEADE, BD LYNN, F REED, GF MINK, CM ROMANI, TA DEFOREST, A DELORIA, MA TI RELATIONSHIPS BETWEEN FUNCTIONAL ASSAYS AND ENZYME IMMUNOASSAYS AS MEASUREMENTS OF RESPONSES TO ACELLULAR AND WHOLE-CELL PERTUSSIS VACCINES SO PEDIATRICS LA English DT Article; Proceedings Paper CT Meeting of the Society-for-Pediatric-Research CY MAY 06, 1992 CL BALTIMORE, MD SP Soc Pediat Res ID BORDETELLA-PERTUSSIS; FIMBRIAE; TOXIN; INFANTS; PURIFICATION; AGGLUTINOGEN; CHILDREN AB Objective. To examine the relationships between functional assays and antigen-specific enzyme immunoassays in sera from a multicenter trial of 13 different experimental acellular pertussis vaccines and 2 licensed whole-cell vaccines, and to determine whether correlations previously observed among assays of specimens from pertussis patients and whole-cell vaccinees would apply to specimens from infants immunized with purified components in acellular vaccines. Methods. Postimmunization sera were assayed for immunoglobulin G antibodies to pertussis toxin (PT), filamentous hemagglutinin, pertactin (PRN), and a mixture of types 2 and 3 fimbriae (FIM) by enzyme-linked immunosorbent assay, for whole-cell agglutinins (AGGs) and for PT-neutralizing antibodies by the Chinese hamster ovary (CHO) cell assay. Assay results were compared for individual sera, as well as for geometric mean antibody concentrations or titers (GMTs) calculated by vaccine or overall. Results. For the 15 vaccines, the PT GMTs were highly correlated with the CHO assay GMTs (r = .92), and the FIM GMTs were highly correlated with the AGG GMTs (r = .96). For individual postvaccination sera, there was a significant correlation between the CHO titers and levels of antibody to PT whether the 15 vaccines were considered separately (.59 less than or equal to r less than or equal to .85) or combined (r = .81). For individual sera from infants immunized with the two whole-cell vaccines or any of the four acellular vaccines containing FIM, a strong correlation between AGG titer and FIM antibody was observed whether the vaccines were considered separately (.83 less than or equal to r less than or equal to .91) or together (r = .86). One vaccine without detectable FIM produced a measurable AGG response; for this vaccine, a moderate but significant correlation (R = .58) between PRN antibody and AGG titer was observed. Conclusion. These data indicate that appropriate antigen-specific enzyme-linked immunosorbent assays will furnish results similar to those provided by the CHO and AGG assays in the evaluation of the immunogenicity of component vaccines. Antibodies to FIM seem to include the most important AGGs; however, there is evidence that agglutination by PRN antibody may be detected in the absence of antibody to FIM. C1 NIAID,DIV MICROBIOL & INFECT DIS,BETHESDA,MD 20892. ST LOUIS UNIV,SCH MED,DEPT PEDIAT,ST LOUIS,MO 63104. TEMPLE UNIV,SCH MED,DEPT MICROBIOL,PHILADELPHIA,PA 19122. TEMPLE UNIV,SCH MED,DEPT PEDIAT,PHILADELPHIA,PA 19122. ST CHRISTOPHERS HOSP CHILDREN,PHILADELPHIA,PA 19133. RP MEADE, BD (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,MAIL CODE HFM 490,ROCKVILLE,MD 20852, USA. FU NIAID NIH HHS [N01-AI72629, N01-AI25135, N01-AI62515] NR 26 TC 18 Z9 18 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 1995 VL 96 IS 3 SU S BP 595 EP 600 PG 6 WC Pediatrics SC Pediatrics GA RU712 UT WOS:A1995RU71200011 PM 7659484 ER PT J AU REED, GF MEADE, BD STEINHOFF, MC AF REED, GF MEADE, BD STEINHOFF, MC TI THE REVERSE CUMULATIVE DISTRIBUTION PLOT - A GRAPHIC METHOD FOR EXPLORATORY ANALYSIS OF ANTIBODY DATA SO PEDIATRICS LA English DT Article ID PARALYTIC POLIOMYELITIS; POLIOVIRUS-VACCINE AB Serologic data often have a wide range and commonly do not approximate a normal distribution. Means, medians, SDs, or other conventional numerical summaries of antibody data may not adequately or fully describe these complex data. The reverse cumulative distribution plot is a graphic tool that completely displays all the data, allows a rapid visual assessment of important details of the distribution, and simplifies comparison of distributions. C1 US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,ROCKVILLE,MD 20857. JOHNS HOPKINS UNIV,DEPT PEDIAT,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,DEPT INT HLTH,BALTIMORE,MD 21218. RP REED, GF (reprint author), NIAID,DIV MICROBIOL & INFECT DIS,6003 EXECUT BLVD,MSC 7630,BETHESDA,MD 20892, USA. NR 10 TC 67 Z9 67 U1 1 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 1995 VL 96 IS 3 SU S BP 600 EP 603 PG 4 WC Pediatrics SC Pediatrics GA RU712 UT WOS:A1995RU71200012 PM 7659485 ER PT J AU HARRIS, BD MOODY, EJ GU, ZQ SKOLNICK, P AF HARRIS, BD MOODY, EJ GU, ZQ SKOLNICK, P TI CONTRIBUTION OF DIAZEPAM-INSENSITIVE GABA(A) RECEPTORS TO THE ALCOHOL ANTAGONIST PROPERTIES OF RO-15-4513 AND RELATED IMIDAZOBENZODIAZEPINES SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE ETHANOL; GABA(A) RECEPTORS; SLEEP TIME; RO 15-4513; ZK 93426; RO 19-4603 ID SPINAL-CORD NEURONS; BENZODIAZEPINE RECEPTORS; INVERSE AGONISTS; MOTOR IMPAIRMENT; HIGH AFFINITIES; BINDING-SITES; ION CURRENT; ETHANOL; RO-15-4513; RO15-4513 AB Both in vivo and in vitro studies have shown that Ro 15-4513 can antagonize many of the pharmacologic actions of ethanol. In contrast to many benzodiazepine receptor (BzR) ligands, Ro 15-4513 binds with high affinity to a novel GABA(A) receptor subtype, referred to as ''diazepam-insensitive'' (DI). This study examined the contribution of DI GABA(A) receptors to the modulation of ethanol-induced sleep time by Ro 15-4513 and related imidazobenzodiazepines e.g., Ro 19-4603, Ro16-6028, and ZG-63 (t-butyl-8-chloro-5,6-dihydro-5-methyl-6-oxo-imidazo 1,5,a 1,4 benzodiazepine-3-carboxylate) that possess high affinities for this GABA(A) receptor subtype. Ro 15-4513 (0.6-5 mg/kg) significantly reduced ethanol (3.5 g/kg, IP) sleep time in mice (p < 0.001, analysis of variance). This effect was not blocked by BzR antagonists ZK 93426 (5 mg/kg) and Ro 14-7437 (5 mg/kg), which possess low affinities for DI but bind with high affinities to other ''diazepam-sensitive'' (DS) GABA(A) receptor isoforms. Although Ro 19-4603 (2.5 mg/kg) also reduced ethanol sleep time (p < 0.01), this effect was attenuated by coadministration of ZK 93426 (2.5 mg/kg). Ro 16-6028 (2.5 mg/kg) prolonged (p < 0.01) ethanol sleep time. However, in the presence of either Ro 14-7437 (5 mg/kg) or ZK 93426 (2.5 mg/kg) ethanol-induced sleep time was reduced to values approaching those obtained with ethanol in the presence of Ro 15-4513. A low dose (2.5 mg/kg) of ZG-63 did not significantly affect alcohol steep time. However, in the presence of ZK 93426, ZG-63 increased sleep time (p < 0.01). In contrast, a higher dose of ZG-63 (7.5 mg/kg) prolonged sleep time, an effect that was attenuated by either ZK 93426 or Ro 14-7437. These findings indicate that although antagonism of ethanol-induced sleep time by Ro 15-4513 is mediated, at least in part, through DI, the contribution of this GABA(A) receptor isoform to the modulation of ethanol-induced sleep time by structurally related imidazobenzodiazepines is more variable. The synthesis of compounds with higher selectivity and a range of intrinsic efficacies at DI GABA(A) receptors is required to better define the role of this receptor isoform in ethanol-induced sleep time. C1 JOHNS HOPKINS UNIV,DEPT ANESTHESIOL & CRIT CARE,BALTIMORE,MD. RP HARRIS, BD (reprint author), NIDDK,NEUROSCI LAB,BLDG 8,ROOM 111,BETHESDA,MD 20892, USA. NR 39 TC 18 Z9 18 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD SEP PY 1995 VL 52 IS 1 BP 113 EP 118 DI 10.1016/0091-3057(95)00052-X PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA RM730 UT WOS:A1995RM73000017 PM 7501652 ER PT J AU WELLER, B AF WELLER, B TI BIOSOCIAL MODELS OF DEMOGRAPHIC BEHAVIOR - AN INTRODUCTION SO POPULATION RESEARCH AND POLICY REVIEW LA English DT Editorial Material DE BIOSOCIAL MODELS; DEMOGRAPHERS; HUMAN BEHAVIOR AB A workshop on biosocial models of demographic behavior was organized to provide information to members of the Social Sciences and Population Study Section (SSP), the group entrusted by the National Institutes of Health (NIH) with the responsibility for conducting the first level of peer review of demographic applications submitted to NIH for possible funding. Some of the variables studies by demographers are biological, e.g., fertility, fecundity, morbidity, and mortality, so demographers are not unaware of biological variables. However, they tend to treat biological variables as something to be explained by social, economic, and psychological factors rather than to be integrated into an explanatory paradigm. This workshop contains papers that focus upon various stages of the life cycle and explore the importance of biosocial variables in explaining selected aspects of human behavior. RP WELLER, B (reprint author), NIH,DIV RES GRANTS,SOCIAL SCI & POPULAT STUDY SECT,6701 ROCKLEDGE DR,ROOM 5204,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-5923 J9 POPUL RES POLICY REV JI Popul. Res. Policy Rev. PD SEP PY 1995 VL 14 IS 3 BP 277 EP 282 DI 10.1007/BF01074392 PG 6 WC Demography SC Demography GA TC322 UT WOS:A1995TC32200001 ER PT J AU HYMOWITZ, N CORLE, D ROYCE, J HARTWELL, T CORBETT, K ORLANDI, M PILAND, N AF HYMOWITZ, N CORLE, D ROYCE, J HARTWELL, T CORBETT, K ORLANDI, M PILAND, N TI SMOKERS BASE-LINE CHARACTERISTICS IN THE COMMIT TRIAL SO PREVENTIVE MEDICINE LA English DT Article ID CIGARETTE-SMOKING; UNITED-STATES; TRENDS; AMERICANS; PREVALENCE; HEALTH; RACE AB Background. Baseline telephone survey data from 10 COMMIT sites were submitted to statistical analyses to compare the smoking characteristics of non-Hispanic white (white), non-Hispanic black (black), Mexican-origin (Mexican), and Puerto Rican-origin (Puerto Rican) smokers. Results. White men and women were more Likely to be classified as ''heavy smokers'' than members of other racial/ethnic groups, although black and Puerto Rican smokers were more likely than whites to increase their smoking rates on weekends. Whites were less likely to report stopping smoking in the past, White and Mexican smokers were most likely to smoke light or ultralight brands and least likely to smoke menthol cigarettes. Blacks were most likely to report smoking their first cigarette of the day within 10 min of waking. Conclusion. The differences and similarities among different groups of smokers may have important implications for understanding patterns of tobacco-related disease in smokers from different racial/ethnic and sex groups. (C) 1995 Academic Press, Inc. C1 NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. AMER HLTH FDN,DIV HLTH PROMOT RES,NEW YORK,NY 10017. RES TRIANGLE INST,CTR MED STAT,RES TRIANGLE PK,NC 27709. UNIV COLORADO,DEPT ANTHROPOL,DENVER,CO 80217. AMER HLTH FDN,DIV HLTH PROMOT RES,NEW YORK,NY 10017. LOVELACE FDN MED EDUC & RES,HLTH SERV RES & EDUC,ALBUQUERQUE,NM 87108. RP HYMOWITZ, N (reprint author), UNIV MED & DENT NEW JERSEY,DEPT PSYCHIAT,ADMC 1430,30 BERGEN ST,NEWARK,NJ 07107, USA. FU NCI NIH HHS [N01-CN-64099] NR 23 TC 16 Z9 16 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD SEP PY 1995 VL 24 IS 5 BP 503 EP 508 DI 10.1006/pmed.1995.1080 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA RU866 UT WOS:A1995RU86600013 PM 8524726 ER PT J AU BROWN, SL SALIVE, ME GURALNIK, JM WALLACE, RB OSTFELD, AM BLAZER, D AF BROWN, SL SALIVE, ME GURALNIK, JM WALLACE, RB OSTFELD, AM BLAZER, D TI DEPRESSIVE SYMPTOMS IN THE ELDERLY - ASSOCIATION WITH TOTAL WHITE BLOOD-CELL COUNT SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE AGING; DEPRESSION; EPIDEMIOLOGY; LEUKOCYTE; NEUROIMMUNOLOGY ID DYSFUNCTION; MORTALITY; DISORDER; ILLNESS; HEALTH; SYSTEM; SAMPLE; CANCER; RISK AB 1. The white blood cell (WBC) count in those with high depressive symptoms and non-depressed participants in the Established Populations for Epidemiologic Studies of the Elderly (EPESE) were compared. 2. Of 3769 participants 10.8% had high depressive symptoms as assessed by the Centers for Epidemiologic Studies Depression (CES-D) Scale. The mean white blood cell count was higher in the high depressive symptoms group compared to the non-depressed group (6.8 +/- 0.12 X 10(9) WBC/1 and 6.5 +/- 0.03 X 10(9) WBC/1, respectively, p<0.01). 3. Because older adults frequently have disabling chronic conditions which could both influence their leukocyte count and cause depressive symptoms, model were developed which controlled for the potential confounding. Even after adjusting for potential confounders, high depressive symptoms were still associated with higher white blood cell counts. C1 NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. UNIV IOWA,DEPT PREVENT MED & ENVIRONM HLTH,IOWA CITY,IA 52242. YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT 06510. DUKE UNIV,MED CTR,DEPT PSYCHIAT,DIV GERIATR PSYCHIAT,DURHAM,NC 27710. NR 33 TC 2 Z9 2 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD SEP PY 1995 VL 19 IS 5 BP 849 EP 860 DI 10.1016/0278-5846(95)00115-C PG 12 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA RX586 UT WOS:A1995RX58600009 PM 8539423 ER PT J AU HAMASAKI, Y ELING, TE AF HAMASAKI, Y ELING, TE TI EGF AND TPA STIMULATE DE-NOVO SYNTHESIS OF PGHS-1 AND PGHS-2 THROUGH DIFFERENT SIGNAL-TRANSDUCTION PATHWAYS SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article ID PROTEIN-KINASE-C; GROWTH-FACTOR RECEPTOR; TYROSINE KINASE; PHORBOL ESTER; CELLS; PHOSPHORYLATION; INHIBITION; STAUROSPORINE; ENHANCE AB Epidermal growth factor (EGF) as well as phorbol 12-myristate 13-acetate (TPA) stimulate de novo synthesis of PGHS (prostaglandin H synthase)-1 and PGHS-2 mRNA, resulting in increased production of PGE, in rat tracheal epithelial cells (RTE, EGV-6 cells), Stimulation of PGE(2) production by TPA is more potent than that by EGF, Staurosporine and H-7, protein kinase C (PKC) inhibitors, suppressed the increase of mRNA and PGE(2) levels caused by TPA, but not that caused by EGF. On the other hand, methyl 2,5-dihydroxycinnamate, a tyrosine kinase inhibitor (TKI), suppressed the increase of mRNA and PGE(2) levels caused by EGF, but not that caused by TPA. These results indicate that EGF stimulates de novo synthesis of PGHS-1 and PGHS-2 mRNA through a signal transduction pathway which is independent from PKC-associated mechanisms but dependent upon the tyrosine kinase activity of the EGF receptor. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. NR 14 TC 12 Z9 12 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 SEP PY 1995 VL 53 IS 3 BP 225 EP 229 DI 10.1016/0952-3278(95)90121-3 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA RT094 UT WOS:A1995RT09400007 PM 7480087 ER PT J AU WALLQVIST, A JERNIGAN, RL COVELL, DG AF WALLQVIST, A JERNIGAN, RL COVELL, DG TI A PREFERENCE-BASED FREE-ENERGY PARAMETERIZATION OF ENZYME-INHIBITOR BINDING - APPLICATIONS TO HIV-1-PROTEASE INHIBITOR DESIGN SO PROTEIN SCIENCE LA English DT Review DE ATOM-ATOM INTERACTIONS; BINDING; MOLECULAR SURFACE; PROTEIN; RECOGNITION ID HUMAN IMMUNODEFICIENCY VIRUS-1; PANCREATIC TRYPSIN-INHIBITOR; PROTEIN-FOLDING THERMODYNAMICS; ACCESSIBLE SURFACE-AREA; MOLAR HEAT-CAPACITY; AMINO-ACID-RESIDUES; AQUEOUS-SOLUTION; LIGAND-BINDING; CRYSTAL-STRUCTURE; TYPE-1 PROTEASE AB The interface between protein receptor-ligand complexes has been studied with respect to their binary interatomic interactions. Crystal structure data have been used to catalogue surfaces buried by atoms from each member of a bound complex and determine a statistical preference for pairs of amino-acid atoms. A simple free energy model of the receptor-ligand system is constructed from these atom-atom preferences and used to assess the energetic importance of interfacial interactions. The free energy approximation of binding strength in this model has a reliability of about +/-1.5 kcal/mol, despite limited knowledge of the unbound states. The main utility of such a scheme lies in the identification of important stabilizing atomic interactions across the receptor-ligand interface. Thus, apart from an overall hydrophobic attraction (Young L, Jernigan RL, Covell DG, 1994, Protein Sci 3:717-729), a rich variety of specific interactions is observed. An analysis of 10 HIV-1 protease inhibitor complexes is presented that reveals a common binding motif comprised of energetically important contacts with a rather limited set of atoms. Design improvements to existing HIV-1 protease inhibitors are explored based on a detailed analysis of this binding motif. C1 NCI,SCI APPLICAT INT CORP,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NCI,MATH BIOL LAB,BETHESDA,MD 20892. RI Jernigan, Robert/A-5421-2012; OI wallqvist, anders/0000-0002-9775-7469 NR 135 TC 111 Z9 112 U1 9 U2 20 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 SEP PY 1995 VL 4 IS 9 BP 1881 EP 1903 PG 23 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RW790 UT WOS:A1995RW79000023 PM 8528086 ER PT J AU MEZZICH, JE AF MEZZICH, JE TI CULTURAL FORMULATION AND COMPREHENSIVE DIAGNOSIS - CLINICAL AND RESEARCH PERSPECTIVES SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID PSYCHIATRIC-DIAGNOSIS AB The Cultural Formulation intends to supplement a standardized multiaxial diagnostic statement by describing the cultural framework of the patient's identity, illness, and context of the clinician-patient relationship. It was developed by the National Institute of Mental Health Culture and Diagnosis Group for incorporation in DSM-IV. Its relevance to clinical care, training, and research can be better understood when it is considered from the viewpoint of a comprehensive diagnostic model. C1 CUNY MT SINAI SCH MED,INT CTR HLTH BEHAV & CULTURE,NEW YORK,NY 10029. NIMH,CULTURE & DIAGNOSIS GRP,BETHESDA,MD 20892. RP MEZZICH, JE (reprint author), CUNY MT SINAI SCH MED,DEPT PSYCHIAT,5TH AVE & 100TH ST,BOX 1230,NEW YORK,NY 10029, USA. NR 28 TC 40 Z9 40 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD SEP PY 1995 VL 18 IS 3 BP 649 EP 657 PG 9 WC Psychiatry SC Psychiatry GA RT638 UT WOS:A1995RT63800015 PM 8545273 ER PT J AU JOHNSON, DN WEINGARTNER, HJ ANDREASON, P GEORGE, DT AF JOHNSON, DN WEINGARTNER, HJ ANDREASON, P GEORGE, DT TI AN EFFECT OF TRIAZOLAM ON VISUAL-ATTENTION AND INFORMATION-PROCESSING SO PSYCHOPHARMACOLOGY LA English DT Article DE BENZODIAZEPINES; TRIAZOLAM; ATTENTION; VISUAL INFORMATION PROCESSING; MEMORY ID MINDS EYES MOVEMENT; SELECTIVE ATTENTION; MODEL; BENZODIAZEPINES; DISSOCIATION; FLUMAZENIL; VOLUNTARY; SEARCH; MEMORY AB This study explored whether benzodiazepines selectively affect aspects of attention and/or visual information processing, as they do memory. A cued visual-search paradigm was employed, using normal volunteers and a single dose of triazolam. This paradigm provided for a detailed examination of two aspects of visual attention and information processing: 1) controlled versus automatic attention allocation (via central and peripheral cues), and 2) the extent to which processing an item in a non-cued location affects performance (via cue-validity). Triazolam, compared to placebo, significantly increased response time, and Drug Condition interacted with Cue-Validity but not Cue-Type. Based on these data, we argue that triazolam does not affect attention allocation but does affect attentional disengagement and/or attention switching mechanisms. RP JOHNSON, DN (reprint author), NIAAA,COGNIT NEUROSCI SECT,BLDG 10,ROOM 3B-19,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 20 TC 17 Z9 17 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD SEP PY 1995 VL 121 IS 2 BP 145 EP 149 DI 10.1007/BF02245623 PG 5 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA RY288 UT WOS:A1995RY28800001 PM 8545518 ER PT J AU SUNDERLAND, T ESPOSITO, G MOLCHAN, SE COPPOLA, R JONES, DW GOREY, J LITTLE, JT BAHRO, M WEINBERGER, DR AF SUNDERLAND, T ESPOSITO, G MOLCHAN, SE COPPOLA, R JONES, DW GOREY, J LITTLE, JT BAHRO, M WEINBERGER, DR TI DIFFERENTIAL CHOLINERGIC REGULATION IN ALZHEIMERS PATIENTS COMPARED TO CONTROLS FOLLOWING CHRONIC BLOCKADE WITH SCOPOLAMINE - A SPECT STUDY SO PSYCHOPHARMACOLOGY LA English DT Article DE SCOPOLAMINE; ALZHEIMERS DISEASE; SPECT; I-QNB; HMPAO; CHOLINERGIC ID CEREBRAL BLOOD-FLOW; MUSCARINIC ACETYLCHOLINE-RECEPTORS; EMISSION TOMOGRAPHY; DISSOCIATION KINETICS; PARKINSONS-DISEASE; SENILE DEMENTIA; RAT-BRAIN; INVIVO; BINDING; HIPPOCAMPUS AB The effects of low-dose chronic scopolamine on measures of cerebral perfusion and muscarinic receptors were tested in eight Alzheimer's disease (AD) subjects and eight elderly controls. Single photon emission computed tomography (SPECT) scans using technetium-labelled hexamethypropylene amine oxide (Tc-99m-HMPAO) to measure cerebral perfusion before and after chronic scopolamine revealed a significant 12% increase in the normal controls (P < 0.01) while the AD subjects showed no significant change. In contrast, the controls showed decreased muscarinic binding as evidence by I-123-quinuclidinyl-4-iodobenzilate (I-123-QNB) labelling after chronic drug (-10%, P < 0.01) whereas the AD subjects showed increased I-123-QNB labelling (+ 8%, P < 0.05). The difference between AD and control subjects was even more marked when the ratio of I-QNB to HMPAO uptake was compared, pointing to a double dissociation in the SPECT results. These data cannot be explained by group differences in cerebral perfusion alone and suggest a differential sensitivity between AD and elderly controls to chronic cholinergic blockade. C1 NIMH,CLIN SCI LAB,GERIATR PSYCHIAT SECT,BETHESDA,MD 20892. NIMH,ST ELIZABETHS HOSP,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NR 79 TC 27 Z9 28 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD SEP PY 1995 VL 121 IS 2 BP 231 EP 241 DI 10.1007/BF02245634 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA RY288 UT WOS:A1995RY28800012 PM 8545529 ER PT J AU SIMONSICK, EM WALLACE, RB BLAZER, DG BERKMAN, LF AF SIMONSICK, EM WALLACE, RB BLAZER, DG BERKMAN, LF TI DEPRESSIVE SYMPTOMATOLOGY AND HYPERTENSION-ASSOCIATED MORBIDITY AND MORTALITY IN OLDER ADULTS SO PSYCHOSOMATIC MEDICINE LA English DT Article DE DEPRESSION; ELDERLY; HYPERTENSION; STROKE; CARDIOVASCULAR MORTALITY ID BODY-MASS INDEX; BLOOD-PRESSURE; MYOCARDIAL-INFARCTION; PHYSICAL ILLNESS; RISK; PREVALENCE; PREDICTORS; SYMPTOMS; OUTCOMES; SURVIVAL AB This study determines, in a population of older adults with diagnosed hypertension, the concurrent association between depressive symptomatology and blood pressure control and the longitudinal association between depressive symptomatology and blood pressure control, stroke, and cardiovascular-related mortality. Data are from the East Boston, Massachusetts; New Haven, Connecticut; and Iowa sites of the Established Populations for Epidemiologic Studies of the Elderly, conducted between 1982 and 1988. Age-adjusted site- and gender-specific analyses were conducted, unadjusted and adjusted for baseline health status. There was no consistent association, cross-sectionally or longitudinally, between depressive symptoms and blood pressure control. Rates of stroke were 2.3 to 2.7 times higher in most subgroups with high depressive symptomatology in contrast to their nondepressed counterparts. Rates of cardiovascular disease-related death were also elevated in most subgroups, achieving statistical significance in women from New Haven and Iowa. This study presents evidence that high depressive symptoms in older adults with diagnosed hypertension may place them at increased risk of stroke and possibly cardiovascular-related death relative to other elderly persons with diagnosed hypertension. Because the fate of stroke in this subpopulation was exceptionally high, further evaluation of the role of depressive symptoms in the progression of hypertensive disease seems warranted. C1 UNIV IOWA,COLL MED,DEPT PREVENT MED & ENVIRONM HLTH,IOWA CITY,IA. DUKE UNIV,MED CTR,SCH MED,DURHAM,NC 27710. YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT 06510. RP SIMONSICK, EM (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,7201 WISCONSIN AVE,SUITE 3C-309,BETHESDA,MD 20892, USA. NR 50 TC 153 Z9 157 U1 2 U2 6 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD SEP-OCT PY 1995 VL 57 IS 5 BP 427 EP 435 PG 9 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA RW799 UT WOS:A1995RW79900003 PM 8552732 ER PT J AU BROWN, LJ KINGMAN, A BRUNELLE, JA SELWITZ, RH AF BROWN, LJ KINGMAN, A BRUNELLE, JA SELWITZ, RH TI MOST US SCHOOLCHILDREN ARE CARIES-FREE IN THEIR PERMANENT TEETH - THIS IS NO MYTH SO PUBLIC HEALTH REPORTS LA English DT Editorial Material ID DENTAL-CARIES; CHILDREN; ATTACK RP BROWN, LJ (reprint author), NIDR,DIV EPIDEMIOL & ORAL DIS PREVENT,BETHESDA,MD 20892, USA. NR 13 TC 11 Z9 12 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD SEP-OCT PY 1995 VL 110 IS 5 BP 531 EP 533 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA TC729 UT WOS:A1995TC72900003 ER PT J AU LIU, MW ROCK, P GRASS, JA HEITMILLER, RF PARKER, SJ SAKIMA, NT WEBB, MD GORMAN, RB BEATTIE, C AF LIU, MW ROCK, P GRASS, JA HEITMILLER, RF PARKER, SJ SAKIMA, NT WEBB, MD GORMAN, RB BEATTIE, C TI DOUBLE-BLIND RANDOMIZED EVALUATION OF INTERCOSTAL NERVE BLOCKS AS AN ADJUVANT TO SUBARACHNOID ADMINISTERED MORPHINE FOR POSTTHORACOTOMY ANALGESIA SO REGIONAL ANESTHESIA LA English DT Article DE SUBARACHNOID; INTERCOSTAL; MORPHINE; POSTOPERATIVE PAIN; PULMONARY FUNCTION; THORACOTOMY AB Background and Objectives. Thoracotomy is associated with pain and compromised pulmonary function. Intercostal nerve blocks (INB) and subarachnoid morphine (SM) act on different portions of the pain pathway. Each is effective for post-thoracotomy pain relief. The combination of these two modalities in relieving post-thoracotomy pain and improving postoperative pulmonary function has not been investigated. Methods. In a double-blind study, 20 patients undergoing lateral thoracotomy for lung resection were randomized to receive 0.5 mg SM preoperatively and INB with bupivacaine (INB+) prior to wound closure or 0.5 mg SM with INB using saline (INB). Visual analog scale pain scores at rest, with cough, and with movement of the ipsilateral arm, forced expiratory volume in 1 second (FEV(1)), and forced vital capacity (FVC) were measured at 4, 24, 48, and 72 hours after the operation. Opioid use was measured during the initial 24 hours after the operation. Results. At 4 hours, the INB+ group demonstrated better FEV(1) (56.6% vs. 40.4% of baseline, P < .05) and FVC values (54.6% vs. 39.6% of baseline, P < .05) and less resting and cough pain (P < .05). However, FEV(1) continued to decline in the INB+ group at 24 hours to lower than the INB- group although pain scores were similar beyond 4 hours. Opioid usage during the first 24 hours was similar (INB-, 16.7 mg vs. INB+, 13.2 mg, P = .7). Conclusions. Although postoperative INB provided modest improvements in pain and pulmonary function when used as an adjuvant to 0.5 mg SM for post-thoracotomy analgesia, the benefits were transient. The authors do not recommend adding INB for patients undergoing lateral thoracotomy who receive 0.5 mg SM. RP LIU, MW (reprint author), NIH,DEPT HLTH & HUMAN SERV,9000 ROCKVILLE PIKE,BLDG 10,ROOM 3C-306,BETHESDA,MD 20892, USA. NR 0 TC 9 Z9 11 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 0146-521X J9 REGION ANESTH JI Reg. Anesth. PD SEP-OCT PY 1995 VL 20 IS 5 BP 418 EP 425 PG 8 WC Anesthesiology SC Anesthesiology GA RW951 UT WOS:A1995RW95100010 PM 8519720 ER PT J AU NOSEK, MA FUHRER, MJ POTTER, C AF NOSEK, MA FUHRER, MJ POTTER, C TI LIFE SATISFACTION OF PEOPLE WITH PHYSICAL-DISABILITIES - RELATIONSHIP TO PERSONAL ASSISTANCE, DISABILITY STATUS, AND HANDICAP SO REHABILITATION PSYCHOLOGY LA English DT Article AB To understand how physical disability affects life satisfaction, the present study focused on possible moderating factors that are associated with those conditions and with life satisfaction. Three possible moderating factors were investigated: (1) level of disability, (2) level of handicap, and (3) self-appraised adequacy of personal assistance. A sample of 45 persons with a variety of physical disabilities who use personal assistance was given the Life Satisfaction Index - A, selected subscales from the Arthritis Impact Measurement Scale, the Craig Handicap Assessment and Report Technique, and a 19-item measure of personal assistance satisfaction. There were significant positive correlations between life satisfaction and both handicap and personal assistance satisfaction. Life satisfaction and degree of disability were not significantly correlated. There was no interaction between disability and personal assistance satisfaction with respect to either life satisfaction or handicap. Results are discussed in terms of Diener's ''bottom-up'' theory and the complex array of factors that contribute to personal assistance satisfaction. C1 NIH,BETHESDA,MD 20892. UNIV GEORGIA,ATHENS,GA 30602. RP NOSEK, MA (reprint author), BAYLOR COLL MED,DEPT PHYS MED & REHABIL,1333 MOURSUND,HOUSTON,TX 77030, USA. NR 23 TC 30 Z9 30 U1 2 U2 2 PU SPRINGER PUBL CO PI NEW YORK PA 536 BROADWAY, NEW YORK, NY 10010-3955 SN 0090-5550 J9 REHABIL PSYCHOL JI Rehabil. Psychol. PD FAL PY 1995 VL 40 IS 3 BP 191 EP 202 DI 10.1037//0090-5550.40.3.191 PG 12 WC Psychology, Clinical; Rehabilitation SC Psychology; Rehabilitation GA TH449 UT WOS:A1995TH44900003 ER PT J AU Seder, RA AF Seder, RA TI The role of IL12 in the regulation of Th1 and Th2 differentiation SO RESEARCH IN IMMUNOLOGY LA English DT Article ID CD4+ T-CELLS; PHENOTYPE DEVELOPMENT; GAMMA PRODUCTION; TRANSGENIC MICE; INTERLEUKIN-4; MACROPHAGES RP Seder, RA (reprint author), NIAID,NIH,BLDG 10,ROOM 11C215,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 27 TC 11 Z9 11 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0923-2494 J9 RES IMMUNOL JI Res. Immunol. PD SEP-OCT PY 1995 VL 146 IS 7-8 BP 473 EP 476 DI 10.1016/0923-2494(96)83018-5 PG 4 WC Immunology SC Immunology GA TW313 UT WOS:A1995TW31300028 PM 8839148 ER PT J AU SchartonKersten, T Denkers, EY Gazzinelli, R Sher, A AF SchartonKersten, T Denkers, EY Gazzinelli, R Sher, A TI Role of IL12 in induction of cell-mediated immunity to Toxoplasma gondii SO RESEARCH IN IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; CD8+ LYMPHOCYTES-T; IFN-GAMMA; EXPERIMENTAL-MODELS; SCID MOUSE; RESISTANCE; INFECTION; MICE; ENCEPHALITIS; CD4+ RP SchartonKersten, T (reprint author), NIAID,NIH,IMMUNOBIOL SECT,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 28 TC 33 Z9 33 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0923-2494 J9 RES IMMUNOL JI Res. Immunol. PD SEP-OCT PY 1995 VL 146 IS 7-8 BP 539 EP 544 DI 10.1016/0923-2494(96)83029-X PG 6 WC Immunology SC Immunology GA TW313 UT WOS:A1995TW31300071 PM 8839159 ER PT J AU Wynn, TA Sher, A AF Wynn, TA Sher, A TI IL12 as an adjuvant for vaccines designed to prevent infection and immunopathology by schistosomes SO RESEARCH IN IMMUNOLOGY LA English DT Article ID CD4+ T-CELLS; IFN-GAMMA; GRANULOMA-FORMATION; INTERFERON-GAMMA; CYTOKINE PRODUCTION; IMMUNE-RESPONSES; MANSONI; INTERLEUKIN-12; IL-4; TH2 RP Wynn, TA (reprint author), NIAID,NIH,PARASIT DIS LAB,IMMUNOBIOL SECT,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Wynn, Thomas/C-2797-2011 NR 56 TC 2 Z9 2 U1 0 U2 1 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0923-2494 J9 RES IMMUNOL JI Res. Immunol. PD SEP-OCT PY 1995 VL 146 IS 7-8 BP 582 EP 589 DI 10.1016/0923-2494(96)83035-5 PG 8 WC Immunology SC Immunology GA TW313 UT WOS:A1995TW31300092 PM 8839165 ER EF