FN Thomson Reuters Web of Science™ VR 1.0 PT J AU SHIMIZU, Y VANSEVENTER, GA ENNIS, E NEWMAN, W HORGAN, KJ SHAW, S AF SHIMIZU, Y VANSEVENTER, GA ENNIS, E NEWMAN, W HORGAN, KJ SHAW, S TI CROSS-LINKING OF THE T-CELL-SPECIFIC ACCESSORY MOLECULES CD7 AND CD28 MODULATES T-CELL ADHESION SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID LYMPHOCYTES-T; EXPRESSION; LFA-1; ACTIVATION; RECEPTOR; INTEGRIN; BINDING AB Regulated adhesion enables T cells to migrate through tissue and transiently interact with an endless succession of cells. Monoclonal antibody (mAb) engagement of the CD3/T cell receptor (TCR) complex results in a rapid and transient augmentation of the adhesion function of LFA-1 and VLA integrin molecules on human T cells. We show in this study that mAb crosslinking of the T cell-specific accessory molecules CD7 and CD28, or treatment with the Ca2+ ionophore A23187, results in the rapid induction of integrin-mediated adhesion to three distinct ligands: the extracellular matrix protein fibronectin, and the cell surface molecules ICAM-1 and VCAM-1. Like CD3 crosslinking, increased adhesion via CD7 and CD28 crosslinking appears to involve both protein kinase C (PKC) and cAMP-dependent protein kinases. In contrast, A23187 induction of adhesion is unaffected by PKC inhibitors. CD7 is preferentially expressed on naive T cells and is unique in being a potent inducer of naive T cell adhesion. Enhanced expression/function of adhesion-inducing molecules thus overcomes relative deficits in adhesion receptor expression. C1 OTSUKA AMER PHARMACEUT INC,DEPT ENDOTHELIAL CELL BIOL,ROCKVILLE,MD 20850. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RP SHIMIZU, Y (reprint author), UNIV MICHIGAN,SCH MED,DEPT MICROBIOL & IMMUNOL,ANN ARBOR,MI 48109, USA. OI Shimizu, Yoji/0000-0001-9760-0288 FU NIAID NIH HHS [AI-3112601] NR 34 TC 202 Z9 203 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 1 PY 1992 VL 175 IS 2 BP 577 EP 582 DI 10.1084/jem.175.2.577 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA HB061 UT WOS:A1992HB06100029 PM 1370688 ER PT J AU TANAKA, T CHU, CC PAUL, WE AF TANAKA, T CHU, CC PAUL, WE TI AN ANTISENSE OLIGONUCLEOTIDE COMPLEMENTARY TO A SEQUENCE IN I-GAMMA-2B INCREASES GAMMA-2B GERMLINE TRANSCRIPTS, STIMULATES B-CELL DNA-SYNTHESIS, AND INHIBITS IMMUNOGLOBULIN SECRETION SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HEAVY-CHAIN TRANSCRIPTS; EPSILON-TRANSCRIPTS; BACTERIAL LIPOPOLYSACCHARIDE; MONOCLONAL-ANTIBODIES; C-EPSILON; INTERLEUKIN-4; EXPRESSION; INDUCTION; SWITCH; MITOGEN AB An antisense phosphorothioate (S)-oligonucleotide to a sequence in the intervening (I) region of the gamma-2b immunoglobulin (Ig) heavy chain gene inhibits Ig secretion by B cells stimulated with lipopolysaccharide (LPS) or LPS plus interleukin 4. It is also a striking stimulant of DNA synthesis by resting B cells. The antisense S-oligonucleotide causes a 10-20-fold increase in the expression of the gamma-2b germline transcript. Among mutants of the antisense S-oligonucleotide, some show all the effects whereas others are inactive. A similar hierarchy exists in the quantitative biological activities of mutant S-oligonucleotides and in their capacity to hybridize to the sense oligonucleotide, strongly suggesting that an I-gamma-2b sequence in the RNA transcript or in the noncoding strand of the DNA is the target of the antisense S-oligonucleotide. The possible relationship of the overexpression of the germline gamma-2b transcript to the biological functions of the I-gamma-2b antisense S-oligonucleotide is discussed. RP TANAKA, T (reprint author), NIAID,IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 27 TC 37 Z9 38 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 1 PY 1992 VL 175 IS 2 BP 597 EP 607 DI 10.1084/jem.175.2.597 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA HB061 UT WOS:A1992HB06100031 PM 1732418 ER PT J AU GEBER, A HIGGINS, DE WATERS, AP BENNETT, JE MCCUTCHAN, TF AF GEBER, A HIGGINS, DE WATERS, AP BENNETT, JE MCCUTCHAN, TF TI SMALL SUBUNIT RIBOSOMAL-RNA OF BLASTOMYCES-DERMATITIDIS - SEQUENCE AND PHYLOGENETIC ANALYSIS SO JOURNAL OF GENERAL MICROBIOLOGY LA English DT Article ID NUCLEOTIDE-SEQUENCE; EVOLUTIONARY IMPLICATIONS; SACCHAROMYCES CEREVISIAE; GENE SEQUENCE; YEAST; EUKARYOTES; KINGDOMS; POSITION AB We determined the small subunit (18S) ribosomal RNA sequence of the dimorphic fungus Blastomyces dermatitidis. The sequence was compared to that of fourteen other eukaryotic organisms, ten of which were higher fungi, and an evolutionary tree was constructed based on these sequences. B. dermatitidis aligned most closely with the Ascomycetes Neurospora crassa and Podospora anserina, in agreement with previous phylogenetic analysis based on morphological criteria. Phase-specific cDNA clones derived by reverse transcription of RNA isolated from the yeast and mycelial phases of B. dermatitidis were also sequenced. The 18S ribosome sequence was found to be the same in both phases. Heterogeneity was found at both the genomic and RNA level at position 1352. C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. EUROPEAN MOLEC BIOL LAB,W-6900 HEIDELBERG,GERMANY. LEIDEN UNIV,PARASITOL LAB,2300 RC LEIDEN,NETHERLANDS. RP GEBER, A (reprint author), NIAID,CLIN INVEST LAB,BETHESDA,MD 20892, USA. RI Waters, Andy/C-9377-2009 OI Waters, Andy/0000-0001-8900-2982 NR 42 TC 5 Z9 5 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1287 J9 J GEN MICROBIOL JI J. Gen. Microbiol. PD FEB PY 1992 VL 138 BP 395 EP 399 PN 2 PG 5 WC Microbiology SC Microbiology GA HE545 UT WOS:A1992HE54500019 PM 1564447 ER PT J AU KIRSHENBAUM, AS GOFF, JP KESSLER, SW MICAN, JM ZSEBO, KM METCALFE, DD AF KIRSHENBAUM, AS GOFF, JP KESSLER, SW MICAN, JM ZSEBO, KM METCALFE, DD TI EFFECT OF IL-3 AND STEM-CELL FACTOR ON THE APPEARANCE OF HUMAN BASOPHILS AND MAST-CELLS FROM CD34+ PLURIPOTENT PROGENITOR CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID C-KIT RECEPTOR; GROWTH-FACTOR; BONE-MARROW; SI-LOCUS; MOUSE; FIBROBLASTS; LIGAND; RAT; KINASE AB Hemopoietic stem cell factor (SCF), which is the ligand for the proto-oncogene c-kit receptor (allelic with W locus) and the product of Sl locus of the mouse, has recently been cloned. The human homologue has also been cloned, and recombinant protein (human rSCF) expressed and purified to homogeneity. To determine the effect of human rSCF in the presence or absence of human rIL-3 on human bone marrow-derived mast cells and basophils, human CD34+ pluripotent progenitor cells, highly enriched (> 99%) from bone marrow mononuclear cells, were cultured over agarose surfaces (interphase cultures) in the presence of human rIL-3, human rIL-3 and increasing concentrations of human rSCF, or human rSCF alone. Over 3 to 4 wk, human rSCF acted synergistically with human rIL-3 at all concentrations, producing a three- to fivefold increase in total, mast cell, and basophil numbers over human rIL-3 alone when used at 100 ng/ml. The percentage of cell types in the human rIL-3 and human rIL-3 plus human rSCF cultures, however, remained the same, with basophils constituting 18 to 35% of the final cultured cells, and mast cells 3% or less of the final cell number. In the presence of human rSCF alone, the combined total percentage of mast cells and basophils was 0 to 1.0%, the majority of cells being macrophages. Mast cells cultured in human rIL-3 plus human rSCF, but not human rIL-3 alone, were berberine sulfate positive, suggesting the presence of heparin proteoglycans within granules. Electron microscopic examination of cultures supplemented with human rIL-3 and rSCF, but not human rIL-3 alone, revealed that after 3 wk in culture, mast cell granules contained tryptase and exhibited scroll, reticular, and homogeneous patterns as seen previously in CD34+/3T3 fibroblast cocultures. Thus, CD34+ cells cultured in the presence of both human rIL-3 and rSCF give rise to cultures containing increased numbers of basophils and mast cells, with the mast cells by ultrastructural studies showing evidence of maturation although the percentages of basophils and mast cells arising in these cultures remained unchanged. C1 HOMEWOOD HOSP,DEPT MED,DIV ALLERGY,BALTIMORE,MD 21211. GEORGETOWN UNIV,MED CTR,DIV MOLEC VIROL & IMMUNOL,ROCKVILLE,MD 20852. USN,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20889. AMGEN INC,THOUSAND OAKS,CA 91320. RP KIRSHENBAUM, AS (reprint author), NIAID,MAST CELL PHYSIOL SECT,CLIN INVEST LAB,BLDG 10,ROOM 11C212,BETHESDA,MD 20892, USA. NR 24 TC 254 Z9 256 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 1992 VL 148 IS 3 BP 772 EP 777 PG 6 WC Immunology SC Immunology GA HB535 UT WOS:A1992HB53500017 PM 1370517 ER PT J AU LEA, RG FLANDERS, KC HARLEY, CB MANUEL, J BANWATT, D CLARK, DA AF LEA, RG FLANDERS, KC HARLEY, CB MANUEL, J BANWATT, D CLARK, DA TI RELEASE OF A TRANSFORMING GROWTH-FACTOR (TGF)-BETA-2-RELATED SUPPRESSOR FACTOR FROM POSTIMPLANTATION MURINE DECIDUAL TISSUE CAN BE CORRELATED WITH THE DETECTION OF A SUBPOPULATION OF CELLS CONTAINING RNA FOR TGF-BETA-2 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID VS-GRAFT REACTION; PREGNANT MICE; ACTIVE SUPPRESSION; FACTOR-BETA; MESSENGER-RNA; INSITU HYBRIDIZATION; SPONTANEOUS-ABORTION; KILLER CELLS; EXPRESSION; HOST AB Postimplantation murine decidual tissue from allopregnant C3H mice has been shown to release in vitro a potent immunosuppressive factor closely related to transforming growth factor (TGF)-beta-2 but slightly lower in apparent molecular weight. Decidual suppressor factor (DSF) activity was first detected in decidual tissue supernatant at day 9.5 of gestation and reached a plateau by day 10.5 to 12.5. By Northern analysis of decidual and placental tissue with a simian TGF-beta-2 probe, two characteristic TGF-beta-2 mRNA transcripts were detected in decidual tissue. In situ hybridization analysis of C3H implant sites, with the simian (pGEM-G1G2) TGF-beta-2 riboprobe, revealed a small population of TGF-beta-2+ cells localized to postimplantation decidua basalis and metrial gland cell area after day 8.5. On and before day 8.5, when DSF was not detectable, few TGF-beta-2 mRNA+ cells were detected. To test for TGF-beta release in situ, sections of uterine tissue were stained with antibody specific for TGF-beta-2, that identified DSF in Western blots. In postimplantation tissues (day 9.5, 12.5) patchy anti-TGF-beta-2 staining was seen over decidual tissue. Before day 9.5, slight and diffuse staining over decidual tissue was present with more marked staining of extradecidual tissue. Very little staining was noted over day 9.5 decidual tissue by using anti-TGF-beta-1 antibody as a control; however, some staining was seen over postimplantation fetal trophoblast and myometrial tissue. Fractionation of disaggregated postimplantation decidua by velocity sedimentation revealed that TGF-beta-2 mRNA+ cells were predominantly small and sedimented in the same fraction(s) as those cells previously shown to release DSF in vitro. Thus, the release of TGF-beta-2 related DSF correlates with the in situ detection of TGF-beta-2 mRNA and the in situ release of TGF-beta-2 peptide. These studies suggest that DSF may be a form of TGF-beta-2 released by a population of small lymphocytic decidual suppressor cells. C1 MCMASTER UNIV,DEPT MED,1200 MAIN ST W,HAMILTON L8N 3Z5,ONTARIO,CANADA. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. MCMASTER UNIV,DEPT BIOCHEM,HAMILTON L8N 3Z5,ONTARIO,CANADA. NR 52 TC 77 Z9 77 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 1992 VL 148 IS 3 BP 778 EP 787 PG 10 WC Immunology SC Immunology GA HB535 UT WOS:A1992HB53500018 PM 1730871 ER PT J AU MUSSO, T ESPINOZADELGADO, I PULKKI, K GUSELLA, GL LONGO, DL VARESIO, L AF MUSSO, T ESPINOZADELGADO, I PULKKI, K GUSELLA, GL LONGO, DL VARESIO, L TI IL-2 INDUCES IL-6 PRODUCTION IN HUMAN MONOCYTES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HEPATOCYTE-STIMULATING FACTOR; HYBRIDOMA GROWTH-FACTOR; TUMOR NECROSIS FACTOR; BLOOD MONOCYTES; INTERLEUKIN-2 RECEPTOR; ENDOTHELIAL-CELLS; GENE-EXPRESSION; INVITRO GROWTH; LYMPHOCYTES-T; FACTOR-BETA AB IL-2 is a potent activator of effector and secretory activities of human monocytes. Since monocytes are an important source of IL-6, we investigated whether IL-2 can induce IL-6 production and whether regulatory circuits can modulate this process. We found that stimulation of monocytes with IL-2 induced expression of IL-6 mRNA and bioactivity in a dose-dependent manner. Production of IL-6 in monocytes can be induced by other cytokines such as IL-1-beta. By using mAb alpha-IL-1-beta we showed that IL-2-induced IL-6 production is not mediated by the autocrine stimulation of IL-1-beta elicited by IL-2. IL-6 induction by monocytes is not a common response to activating signals because IFN-gamma did not induce IL-6 expression under conditions in which it elicits tumoricidal activity. In contrast, IFN-gamma could completely abrogate the induction of IL-6 expression by IL-1-beta but did not affect the levels of mRNA and the secretion of IL-2-elicited IL-6. We have previously reported that transforming growth factor-beta inhibits IL-6 production in response to IL-1-beta. Studies on the inhibitory activity of transforming growth factor-beta demonstrated that this cytokine differs from IFN-gamma because it inhibited both IL-1- and IL-2-induced IL-6 expression. These data demonstrate that, in human monocytes, both IL-1 and IL-2 stimulate IL-6 expression by independent mechanisms that can be dissociated by the susceptibility to the inhibitory effect of IFN-gamma. IL-6 production is also down-regulated by TGF-beta, whose inhibitory activity is stimulus unrelated. C1 NCI,FREDERICK CANC RES & DEV CTR,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702. RP MUSSO, T (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV,BLDG 560,FREDERICK,MD 21702, USA. RI varesio, luigi/J-8261-2016 OI varesio, luigi/0000-0001-5659-2218 FU NCI NIH HHS [N01-CO-74102] NR 44 TC 72 Z9 73 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 1992 VL 148 IS 3 BP 795 EP 800 PG 6 WC Immunology SC Immunology GA HB535 UT WOS:A1992HB53500020 PM 1730872 ER PT J AU POLITIS, AD SIVO, J DRIGGERS, PH OZATO, K VOGEL, SN AF POLITIS, AD SIVO, J DRIGGERS, PH OZATO, K VOGEL, SN TI MODULATION OF INTERFERON CONSENSUS SEQUENCE BINDING-PROTEIN MESSENGER-RNA IN MURINE PERITONEAL-MACROPHAGES - INDUCTION BY IFN-GAMMA AND DOWN-REGULATION BY IFN-ALPHA, DEXAMETHASONE, AND PROTEIN-KINASE INHIBITORS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IA-ANTIGEN EXPRESSION; TUMOR NECROSIS FACTOR; DOUBLE-STRANDED-RNA; NUCLEAR FACTORS; TRANSCRIPTIONAL ACTIVATION; TUMORICIDAL ACTIVITY; 2-5A SYNTHETASE; FC RECEPTOR; RIFN-GAMMA; CELL-LINE AB IFN play a central role in the activation of macrophages by inducing the expression of several proteins which, in turn, result in increased functional capabilities. Homologous interferon responsive sequences have been found in many IFN-inducible genes, and the gene for a protein that binds these sequences (interferon consensus sequence binding protein, ICSBP) has recently been cloned. In this study, the regulation of ICSBP mRNA induction by IFN-gamma was characterized in murine thioglycolate-elicited peritoneal macrophages. Northern blot analysis revealed two ICSBP mRNA species from these cells. Steady-state levels of both of these species were elevated by IFN-gamma at doses consistent with many IFN-gamma-induced macrophage functional responses. ICSBP mRNA levels increased within 1 h of IFN-gamma treatment, peaked between 4 and 6 h, and subsequently declined to approach baseline levels by approximately 24 h. IFN-alpha, at a concentration shown previously to modulate macrophage surface markers and functions, had no effect on ICSBP message levels alone, but antagonized the IFN-gamma-induction of ICSBP mRNA. IFN-gamma-induction of ICSBP mRNA is resistant to cycloheximide but sensitive to protein kinase inhibitors (H7, H8, HA-1004, staurosporine) at doses that suggest that protein kinase C is a likely target. ICSBP mRNA induction is also inhibited by dexamethasone, a synthetic glucocorticoid, well known as an anti-inflammatory drug capable of influencing gene expression in macrophages. The characterization of ICSBP mRNA regulation should help identify functions for this putative IFN trans-acting factor in macrophage activation. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT MICROBIOL,BETHESDA,MD 20814. NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-18797] NR 67 TC 59 Z9 59 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 1992 VL 148 IS 3 BP 801 EP 807 PG 7 WC Immunology SC Immunology GA HB535 UT WOS:A1992HB53500021 PM 1730873 ER PT J AU CARRENO, BM TURNER, RV BIDDISON, WE COLIGAN, JE AF CARRENO, BM TURNER, RV BIDDISON, WE COLIGAN, JE TI OVERLAPPING EPITOPES THAT ARE RECOGNIZED BY CD8+ HLA CLASS-I-RESTRICTED AND CD4+ CLASS-II-RESTRICTED CYTOTOXIC LYMPHOCYTES-T ARE CONTAINED WITHIN AN INFLUENZA NUCLEOPROTEIN PEPTIDE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL; VIRUS; MOLECULES; ANTIGEN; SPECIFICITY; BINDING; IDENTIFICATION; RECEPTOR; HELP AB Viral epitopes that are recognized by both HLA class I-restricted and class II-restricted T cells have been defined for a type A influenza virus nucleoprotein (NP) peptide. CD8+ and CD4+ CTL lines have been generated against a synthetic peptide encompassing residues 335 to 349 of NP that are restricted by HLA-B37 and HLA-DQw5, respectively. Both of these CTL populations were capable of specifically lysing influenza A virus-infected targets, indicating that a naturally processed NP peptide(s) was being mimicked by the NP (335-349) peptide. Amino acid residues that are critical for recognition of this NP determinant in the context of HLA-B37 and HLA-DQw5 were investigated by the use of panels of truncated and alanine-substituted NP peptides. The results demonstrate that: 1) truncations in the amino- or carboxy-terminal ends differentially affect CD8+ and CD4+ CTL recognition; 2) the NP (335-349) sequence contains two octapeptide epitopes that share a core of six amino acid residues (NP 338-343); and 3) alanine substitutions at five of these residues abrogated recognition by at least one of the CD8+ and CD4+ CTL lines. Thus, these class I- and class II-restricted CTL lines recognize similar but distinct epitopes, and different structural features of the NP peptide are required for presentation by HLA-B37 and HLA-DQw5. Comparison of the amino acid sequences of the NP peptide presented by HLA-B37 and HLA-DQw5 with other peptides known to be presented by both class I and class II molecules revealed a common motif among these peptides. C1 NIAID,BIOL RESOURCES BRANCH,BETHESDA,MD 20892. RP CARRENO, BM (reprint author), NINCDS,BIOL RESOURCES BRANCH,MOLEC IMMUNOL SECT,BLDG 4,ROOM 413,BETHESDA,MD 20892, USA. NR 41 TC 41 Z9 41 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 1992 VL 148 IS 3 BP 894 EP 899 PG 6 WC Immunology SC Immunology GA HB535 UT WOS:A1992HB53500034 PM 1370522 ER PT J AU BOGNER, MP VOSS, SD BECHHOFER, R HANK, JA ROPER, M POPLACK, D HAMMOND, D SONDEL, PM AF BOGNER, MP VOSS, SD BECHHOFER, R HANK, JA ROPER, M POPLACK, D HAMMOND, D SONDEL, PM TI SERUM CD25 LEVELS DURING INTERLEUKIN-2 THERAPY - DOSE DEPENDENCE AND CORRELATIONS WITH CLINICAL TOXICITY AND LYMPHOCYTE SURFACE SCD25 EXPRESSION SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE SOLUBLE INTERLEUKIN-2 RECEPTOR; INTERLEUKIN-2 TOXICITY; INTERLEUKIN-2 ID REPETITIVE WEEKLY CYCLES; PURIFIED HUMAN INTERLEUKIN-2; RECOMBINANT INTERLEUKIN-2; ADVANCED CANCER; KILLER ACTIVITY; PHASE-I; RECEPTOR; CELLS; INVIVO; INFUSION AB Using an enzyme-linked immunosorbent assay (ELISA), we have measured serum levels of a soluble form of the p55 subunit of the interleukin-2 receptor complex, soluble CD25 (sCD25), at regular intervals in the sera of 51 pediatric and adult cancer patients receiving recombinant human interleukin-2 (IL-2). The IL-2 was administered in repetitive weekly cycles alone or in combination with lymphokine-activated killer (LAK) cells. Levels of CD25 correlated with clinical toxicities reflected by nadir blood pressures, percentages of weight gained, and minimum Karnofsky performances during IL-2 therapy. Coadministration of autologous in vitro activated LAK cells together with IL-2 did not significantly affect the pattern of sCD25 release relative to administration of IL-2 alone. Examination of sCD25 release in response to different doses of IL-2 revealed a statistically significant dose effect of IL-2 on the sCD25 levels in patient sera. In addition, the level of sCD25 in patient sera also correlated strongly with expression of CD25 on the surface of peripheral blood lymphocytes (PBL) obtained from patients following IL-2 therapy. These studies demonstrate the utility of the sCD25 ELISA as a clinical tool for monitoring patients on treatment regimens that include IL-2. C1 UNIV WISCONSIN,DEPT HUMAN ONCOL,MADISON,WI 53706. UNIV WISCONSIN,DEPT PEDIAT,MADISON,WI 53706. UNIV WISCONSIN,DEPT GENET,MADISON,WI 53706. NCI,BETHESDA,MD 20892. CHILDRENS CANC STUDY GRP,PASADENA,CA. FU NCI NIH HHS [CA-14520, CM-87290, CA-32685] NR 30 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD FEB PY 1992 VL 11 IS 2 BP 111 EP 118 DI 10.1097/00002371-199202000-00005 PG 8 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA HA090 UT WOS:A1992HA09000005 PM 1571333 ER PT J AU HOOK, EW CANNON, RO NAHMIAS, AJ LEE, FF CAMPBELL, CH GLASSER, D QUINN, TC AF HOOK, EW CANNON, RO NAHMIAS, AJ LEE, FF CAMPBELL, CH GLASSER, D QUINN, TC TI HERPES-SIMPLEX VIRUS-INFECTION AS A RISK FACTOR FOR HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION IN HETEROSEXUALS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID SEXUALLY-TRANSMITTED DISEASES; HIV INFECTION; TYPE-2 INFECTION; HOMOSEXUAL MEN; GENITAL HERPES; ASSOCIATION; ACQUISITION; SEROCONVERSION; GLYCOPROTEIN; SYPHILIS AB To determine if infection with herpes simplex virus (HSV) type 2 is associated with human immunodeficiency virus (HIV) type 1 infection among patients attending sexually transmitted diseases clinics, a case-control study was done on coded sera from 179 HIV-1-infected patients and 367 age-, race-, and gender-matched HIV-1-seronegative patients. Although only 13 (2.3%) of 546 patients had a history of genital herpes treatment, 72% and 56.6%, respectively, had serologic evidence of prior infection with HSV-1 and -2. HSV-1 antibody prevalence was similar among both patient groups; however, HSV-2 antibodies were more common among these infected with HIV-1. Among heterosexual men, 62.7% of those infected with HIV-1 had HSV-2 antibodies compared with 46.7% of those not infected (P < .01). The HSV-2 seroprevalence among women with or without HIV infection was 78.1% and 57.7%, respectively (P < .02). A history of intravenous drug use and a reactive serologic test for syphilis were each independently associated with HIV-1 infection in heterosexuals. These data suggest that the two most common causes of genital ulcerative disease in the United States, genital herpes and syphilis, may contribute to increased risk for HIV-1 infection among heterosexuals. C1 JOHNS HOPKINS UNIV,SCH MED,DIV INFECT DIS,BALTIMORE,MD 21205. BALTIMORE CTY DEPT HLTH,BALTIMORE,MD. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. CTR DIS CONTROL,DIV STD HIV INFECT,ATLANTA,GA 30333. EMORY UNIV,SCH MED,DEPT PEDIAT,DIV INFECT DIS EPIDEMIOL & IMMUNOL,ATLANTA,GA 30322. RI Quinn, Thomas/A-2494-2010 FU NIAID NIH HHS [AI-19554, AI-27727] NR 26 TC 212 Z9 214 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB PY 1992 VL 165 IS 2 BP 251 EP 255 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA HF387 UT WOS:A1992HF38700008 PM 1309846 ER PT J AU LIPKA, JJ MIYOSHI, I HADLOCK, KG REYES, GR CHOW, TP BLATTNER, WA SHAW, GM HANSON, CV GALLO, D CHAN, L FOUNG, SKH AF LIPKA, JJ MIYOSHI, I HADLOCK, KG REYES, GR CHOW, TP BLATTNER, WA SHAW, GM HANSON, CV GALLO, D CHAN, L FOUNG, SKH TI SEGREGATION OF HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I AND TYPE-II INFECTIONS BY ANTIBODY REACTIVITY TO UNIQUE VIRAL EPITOPES SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TROPICAL SPASTIC PARAPARESIS; HUMAN MONOCLONAL-ANTIBODY; HTLV-II; C RETROVIRUS; DRUG-ABUSERS; LEUKEMIA; LYMPHOMA; REGION AB A recombinant protein of the human T cell lymphotropic virus type I (HTLV-I) gp46 outer membrane envelope, MTA-4 (residues 129-203), reacted by Western blot with sera from HTLV-I-infected individuals from the United States and Jamaica but not with 24 (10%) of 242 Japanese sera. A related gp46 recombinant protein, MTA-1 (residues 162-209), reacted with all 58 sera from HTLV-I-infected US and Jamaican individuals and 238 of 242 sera from infected Japanese (combined sensitivity of 99%). Neither recombinant showed reactivity to sera from HTLV-II-infected individuals or uninfected controls. The reactivity of recombinant proteins containing the region of HTLV-II gp46 analogous to MTA-1 was also evaluated by Western blot: GH2-K15 (residues 157-205) and GH2-K55 (residues 162-205) reacted with 88 (98%) and 89 (99%), respectively, of 90 sera from HTLV-II-infected individuals but not with sera from HTLV-I-infected individuals or uninfected controls. These recombinant proteins should permit the development of assays to unambiguously confirm and differentiate HTLV-I and HTLV-II infections. C1 STANFORD UNIV,MED CTR,SCH MED,DEPT PATHOL,STANFORD,CA 94305. GENELABS INC,DEPT MOLEC VIROL,REDWOOD CITY,CA. GENELABS INC,DEPT ANALYT & PROC BIOCHEM,REDWOOD CITY,CA. STATE CALIF DEPT HLTH SERV,CALIF VIRAL & RICKETTSIAL DIS LAB,BERKELEY,CA. KOCHI MED SCH,DEPT MED,NANKOKU,KOCHI 78151,JAPAN. NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL. DIAGNOST BIOTECHNOL LTD,SINGAPORE,SINGAPORE. FU NHLBI NIH HHS [HL-33811]; NIDA NIH HHS [DA-06596] NR 25 TC 77 Z9 78 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB PY 1992 VL 165 IS 2 BP 268 EP 272 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA HF387 UT WOS:A1992HF38700011 PM 1370526 ER PT J AU STEIN, DS KORVICK, JA VERMUND, SH AF STEIN, DS KORVICK, JA VERMUND, SH TI CD4+ LYMPHOCYTE CELL ENUMERATION FOR PREDICTION OF CLINICAL COURSE OF HUMAN-IMMUNODEFICIENCY-VIRUS DISEASE - A REVIEW SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID AIDS-RELATED COMPLEX; PLACEBO-CONTROLLED TRIAL; PNEUMOCYSTIS-CARINII PNEUMONIA; SEROPOSITIVE HOMOSEXUAL MEN; PHASE-I TRIAL; HIV-INFECTION; DOUBLE-BLIND; P24 ANTIGEN; BETA-2-MICROGLOBULIN LEVEL; 2',3'-DIDEOXYINOSINE DDI AB Over the last 10 years the appreciation of the full breadth of the spectrum of human immunodeficiency virus (HIV) infection has gradually increased; it is now known that AIDS represents merely the end stage of this progressive infectious process. The surrogate marker that most closely correlates with the stage of HIV infection is the CD4+, or T helper, cell count. Because this count is relied on in making important therapeutic decisions, it is of paramount importance that clinicians be cognizant of and fully understand the multiple factors that can influence this parameter: the variability of the count from day to day and from morning to night, the influence of intercurrent viral infections, the influence of drugs. In this AIDS Commentary, Sten H. Vermund and his colleagues at the National Institutes of Health discuss these issues and put the CD4+ cell count into a lucid and practical clinical perspective. C1 NIAID,EPIDEMIOL BRANCH,BETHESDA,MD 20892. RP STEIN, DS (reprint author), NIAID,DIV AIDS,CLIN RES PROGRAM,MED BRANCH,6003 EXECUT BLVD,BETHESDA,MD 20892, USA. OI Vermund, Sten/0000-0001-7289-8698 FU NIAID NIH HHS [AI-32535, AI-72632, AI-72634] NR 78 TC 267 Z9 270 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 FEB PY 1992 VL 165 IS 2 BP 352 EP 363 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA HF387 UT WOS:A1992HF38700022 PM 1346152 ER PT J AU MILLER, CJ ALEXANDER, NJ VOGEL, P ANDERSON, J MARX, PA AF MILLER, CJ ALEXANDER, NJ VOGEL, P ANDERSON, J MARX, PA TI MECHANISM OF GENITAL TRANSMISSION OF SIV - A HYPOTHESIS BASED ON TRANSMISSION STUDIES AND THE LOCATION OF SIV IN THE GENITAL-TRACT OF CHRONICALLY INFECTED FEMALE RHESUS MACAQUES SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article; Proceedings Paper CT 4TH MEETING ON NONHUMAN PRIMATE MODELS FOR AIDS CY NOV 06-09, 1991 CL WASHINGTON REG PRIMATE RES CTR, SEATTLE, WA HO WASHINGTON REG PRIMATE RES CTR DE VAGINAL MUCOSA; SIV; VIRUS DISSEMINATION ID HUMAN-IMMUNODEFICIENCY-VIRUS; LANGERHANS CELLS; CERVICAL EPITHELIUM; ANTIBODIES; SECRETIONS; WOMEN; AIDS AB To understand the biologic processes involved in transmission of HIV, we examined the genital tracts of chronically infected female macaques and localized SIV-infected cells. SIV was found in the genital tract of 12 of 16 animals and SIV-infected cells were located in the cervix and vagina. Inoculation of cell-free SIV into the blind vaginal pouch of hysterectomized macaques resulted in systemic infection. We propose a hypothesis to explain the early events in the genital transmission of SIV. C1 NICHHD,BETHESDA,MD 20892. NEW MEXICO STATE UNIV,NEW MEXICO REG PRIMATE RES LAB,LAS CRUCES,NM 88003. RP MILLER, CJ (reprint author), UNIV CALIF DAVIS,CALIF PRIMATE RES CTR,DAVIS,CA 95616, USA. FU NCRR NIH HHS [RR00169] NR 20 TC 97 Z9 98 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD FEB-MAY PY 1992 VL 21 IS 2-3 BP 64 EP 68 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA HW208 UT WOS:A1992HW20800004 PM 1433268 ER PT J AU HAIGWOOD, NL MISHER, L CHIN, SM BLAIR, M PLANELLES, V SCANDELLA, CJ STEIMER, KS GARDNER, MB YILMA, T HIRSCH, VM JOHNSON, PR AF HAIGWOOD, NL MISHER, L CHIN, SM BLAIR, M PLANELLES, V SCANDELLA, CJ STEIMER, KS GARDNER, MB YILMA, T HIRSCH, VM JOHNSON, PR TI CHARACTERIZATION OF GROUP-SPECIFIC ANTIBODIES IN PRIMATES - STUDIES WITH SIV ENVELOPE IN MACAQUES SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article; Proceedings Paper CT 4TH MEETING ON NONHUMAN PRIMATE MODELS FOR AIDS CY NOV 06-09, 1991 CL WASHINGTON REG PRIMATE RES CTR, SEATTLE, WA HO WASHINGTON REG PRIMATE RES CTR DE SIV; HIV; ENVELOPE GLYCOPROTEIN; NEUTRALIZING ANTIBODIES; MACAQUES ID GLYCOPROTEIN GP120; CHIMPANZEES; PROTECTION; CHALLENGE; INFECTION AB Sera from SIV-infected macaques were found to contain antibodies that reacted with conformation-dependent, group-specific determinants on the SIV envelope protein gp130. These conformation-dependent antibodies exhibited virus neutralizing activity; their presence was associated with protection in vaccine studies. The properties of these antibodies are quite similar to those that have been identified in sera from HIV-infected human subjects. These data suggest that the SIV envelope gp130 remains a candidate for subunit vaccine studies. C1 UNIV CALIF DAVIS,DAVIS,CA 95616. NIAID,LID,BETHESDA,MD 20892. RP HAIGWOOD, NL (reprint author), CHIRON CORP,DEPT VIROL,4560 HORTON ST,EMERYVILLE,CA 94608, USA. RI Johnson, Philip/A-6892-2009 FU NIAID NIH HHS [U01AI29207] NR 25 TC 13 Z9 13 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD FEB-MAY PY 1992 VL 21 IS 2-3 BP 82 EP 90 PG 9 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA HW208 UT WOS:A1992HW20800007 PM 1433271 ER PT J AU HU, SL ABRAMS, K MISHER, L STALLARD, V MORAN, P ZARLING, JM LANGLOIS, AJ KULLER, L MORTON, WR BENVENISTE, RE AF HU, SL ABRAMS, K MISHER, L STALLARD, V MORAN, P ZARLING, JM LANGLOIS, AJ KULLER, L MORTON, WR BENVENISTE, RE TI EVALUATION OF PROTECTIVE EFFICACY OF RECOMBINANT SUBUNIT VACCINES AGAINST SIMIAN IMMUNODEFICIENCY VIRUS-INFECTION OF MACAQUES SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article; Proceedings Paper CT 4TH MEETING ON NONHUMAN PRIMATE MODELS FOR AIDS CY NOV 06-09, 1991 CL WASHINGTON REG PRIMATE RES CTR, SEATTLE, WA HO WASHINGTON REG PRIMATE RES CTR DE ENVELOPE GLYCOPROTEINS; VACCINIA VIRUS; BACULOVIRUS; NEUTRALIZING ANTIBODIES; HIV-1 VACCINE AB Simian immunodeficiency virus (SIV) was used as a model to study the protective efficacy of an immunization regimen currently being evaluated as candidate vaccines against HIV in human subjects. Four Macaca fascicularis were first immunized with recombinant vaccinia virus expressing the envelope glycoprotein gp160 of SIV(mne) and then boosted with subunit gp160. Both cell-mediated and humoral immune responses against SIV, including neutralizing antibodies, were elicited. The macaques were shown to be protected from a homologous virus infection as determined by serology, lymphocyte cocultivation, polymerase chain reactions and in vivo transmission analyses. Four unimmunized control animals were readily infected. However, viremia in infected control animals could decrease substantially following the initial phase of infection so that persistent infection might not be readily detectable. C1 UNIV WASHINGTON,SEATTLE,WA 98195. DUKE UNIV,MED CTR,DURHAM,NC 27710. NCI,FREDERICK,MD 21701. RP HU, SL (reprint author), BRISTOL MYERS SQUIBB,PHARMACEUT RES INST,3005 1ST AVE,SEATTLE,WA 98121, USA. RI Hu, Shiu-Lok/A-3196-2008 OI Hu, Shiu-Lok/0000-0003-4336-7964 FU NCRR NIH HHS [RR00166]; NIAID NIH HHS [AI 26503, R01AI28065] NR 18 TC 18 Z9 18 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD FEB-MAY PY 1992 VL 21 IS 2-3 BP 119 EP 125 PG 7 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA HW208 UT WOS:A1992HW20800012 PM 1433262 ER PT J AU ROSENBERG, YJ SHAFFERMAN, A WHITE, BD PAPERMASTER, SF LEON, E EDDY, GA BENVENISTE, R BURKE, DS LEWIS, MG AF ROSENBERG, YJ SHAFFERMAN, A WHITE, BD PAPERMASTER, SF LEON, E EDDY, GA BENVENISTE, R BURKE, DS LEWIS, MG TI VARIATION IN THE CD4+ AND CD8+ POPULATIONS IN LYMPH-NODES DOES NOT REFLECT THAT IN THE BLOOD DURING SIV(MNE/E11S) INFECTION OF MACAQUES SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article; Proceedings Paper CT 4TH MEETING ON NONHUMAN PRIMATE MODELS FOR AIDS CY NOV 06-09, 1991 CL WASHINGTON REG PRIMATE RES CTR, SEATTLE, WA HO WASHINGTON REG PRIMATE RES CTR DE CD4+; CD8+ CELLS; LYMPH NODES; BLOOD; SIV; RHESUS MACAQUES ID IMMUNODEFICIENCY VIRUS; LYMPHOCYTES-T; AIDS; SUBSETS; UCHL1 AB The decline in the CD4% and CD4/CD8 ratios have been compared in lymph nodes and blood from SIV(MNE/E11S) infected rhesus macaques. The results indicate that loss from the LN CD4+ cell pool does not occur until CD4/CD8 ratios of < 0.5 is reached in blood. These changes also correlate with the ability to isolate virus from the blood and the transition of CD45RA(hi) to highly activated CD45RA(lo) CD8+ cells both of which may play a role in eliminating CD4+ cells. In end-stage disease, CD8+ cells also decline in LN and mitogen responsiveness no longer exists in any nodes. Interestingly at this stage, the circulating CD8% increases significantly and represents the only source of functional T cells remaining in the body. C1 NCI,FREDERICK CANC RES FACIL,FREDERICK,MD 21701. WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. RP ROSENBERG, YJ (reprint author), HENRY M JACKSON FDN RES LAB,1500 E GUDE DR,ROCKVILLE,MD 20850, USA. OI /0000-0002-5704-8094 NR 21 TC 14 Z9 14 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD FEB-MAY PY 1992 VL 21 IS 2-3 BP 131 EP 137 PG 7 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA HW208 UT WOS:A1992HW20800014 PM 1359148 ER PT J AU TICEHURST, J POPKIN, TJ BRYAN, JP INNIS, BL DUNCAN, JF AHMED, A IQBAL, M MALIK, I KAPIKIAN, AZ LEGTERS, LJ PURCELL, RH AF TICEHURST, J POPKIN, TJ BRYAN, JP INNIS, BL DUNCAN, JF AHMED, A IQBAL, M MALIK, I KAPIKIAN, AZ LEGTERS, LJ PURCELL, RH TI ASSOCIATION OF HEPATITIS-E VIRUS WITH AN OUTBREAK OF HEPATITIS IN PAKISTAN - SEROLOGIC RESPONSES AND PATTERN OF VIRUS EXCRETION SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE ENTERICALLY TRANSMITTED NON-A; NON-B (ET-NANB) HEPATITIS; EPIDEMIC; IMMUNE ELECTRON MICROSCOPY (IEM); ANTIBODY; VIRUS PARTICLES ID NON-B-HEPATITIS; TRANSMITTED NON-A; IMMUNE ELECTRON-MICROSCOPY; CYNOMOLGUS MACAQUES; PARTICLES; EPIDEMIC; ANTIGEN; GASTROENTERITIS; IDENTIFICATION; QUANTITATION AB Hepatitis E virus (HEV), a positive-strand RNA agent, has been associated with enterically transmitted non-A, non-B hepatitis in Asia, Africa, and Mexico. To evaluate the role of HEV in an outbreak of hepatitis in Pakistan, we used immune electron microscopy to detect 1) antibody to HEV, for evidence of infection, and 2) virus, to determine the pattern of HEV excretion. Paired sera from 2 patients were assayed for antibody by using reference HEV: one seroconverted, an atypical finding for HEV infections; the other had high levels of anti-HEV in both sera. Virus particles with the size (29 x 31 nm) and morphology of HEV were detected in feces from 10 of 85 patients and serologically identified as HEV by using reference antibodies from an HEV infected chimpanzee. One of these HEV-containing specimens was collected 9 days before the onset of jaundice; it was among feces from 38 outpatients with nonspecific symptoms and biochemical hepatitis, 12 of whom subsequently developed jaundice. The other 9 feces with HEV were among 36 collected within 7 days of the onset of acute icteric hepatitis; all 11 feces from days 8 to 15 were negative for HEV. Fecal concentrations of HEV appeared to be lower than those of many enteric viruses: only one specimen contained as many as 5 particles per EM grid square. It is concluded that HEV was etiologically associated with the epidemic and was predominantly excreted at very low levels during the first week of jaundice. C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT PREVENT MED & BIOMETR,BETHESDA,MD 20814. ARMED FORCE INST MED SCI,DEPT VIROL,BANGKOK,THAILAND. ARMY MED COLL,PAKISTAN US LAB SEROEPIDEMIOL,RAWALPINDI,PAKISTAN. RP TICEHURST, J (reprint author), WALTER REED ARMY MED CTR,DEPT VIRAL DIS,WASHINGTON,DC 20307, USA. RI Ticehurst, John/I-7532-2012 NR 50 TC 51 Z9 51 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD FEB PY 1992 VL 36 IS 2 BP 84 EP 92 DI 10.1002/jmv.1890360205 PG 9 WC Virology SC Virology GA HB785 UT WOS:A1992HB78500004 PM 1583470 ER PT J AU BEUTLER, JA CARDELLINA, JH MCMAHON, JB BOYD, MR AF BEUTLER, JA CARDELLINA, JH MCMAHON, JB BOYD, MR TI ANTI-HIV AND CYTOTOXIC ALKALOIDS FROM BUCHENAVIA-CAPITATA SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID AGENTS; ASSAY AB The anti-HIV activity in the organic solvent extract of leaves of Buchenavia capitata was traced to a series of known flavonoid alkaloids, which represent a new chemotype for anti-HIV activity. The C-13-nmr assignments for this series of compounds have been revised. O-Demethylbuchenavianine {1} was the most active compound of the series but produced only moderate cytoprotective effects against HIV in cultured human lymphoblastoid (CEM-SS) cells. Compound 1 was cytotoxic also in the NCI human disease-oriented in vitro tumor screening panel and produced a pattern of modest differential cellular sensitivity. C1 NCI,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21701. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,NAT PROD BRANCH,FREDERICK,MD 21702. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 NR 14 TC 36 Z9 38 U1 3 U2 7 PU AMER SOC PHARMACOGNOSY PI CINCINNATI PA LLOYD LIBRARY & MUSEUM 917 PLUM ST, CINCINNATI, OH 45202 SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD FEB PY 1992 VL 55 IS 2 BP 207 EP 213 DI 10.1021/np50080a008 PG 7 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA HD460 UT WOS:A1992HD46000008 PM 1624941 ER PT J AU CRAGG, GM AF CRAGG, GM TI DISTRIBUTION OF MATERIALS FROM THE NATURAL-PRODUCTS REPOSITORY OF THE NATIONAL CANCER INSTITUTE (NCI) SO JOURNAL OF NATURAL PRODUCTS LA English DT Note RP CRAGG, GM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BLDG 1052,ROOM 109,FREDERICK,MD 21702, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC PHARMACOGNOSY PI CINCINNATI PA LLOYD LIBRARY & MUSEUM 917 PLUM ST, CINCINNATI, OH 45202 SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD FEB PY 1992 VL 55 IS 2 BP 265 EP 265 PG 1 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA HD460 UT WOS:A1992HD46000023 PM 1624945 ER PT J AU BIHARI, K PIGOTT, TA HILL, JL MURPHY, DL AF BIHARI, K PIGOTT, TA HILL, JL MURPHY, DL TI BLEPHAROSPASM AND OBSESSIVE-COMPULSIVE DISORDER SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID TOURETTES SYNDROME AB Although essential blepharospasm is considered to be a form of focal dystonia, many patients with blepharospasm have been noted to have concomitant depression, anxiety, phobias, hypochondriasis, and other emotional and behavioral disorders, suggesting a psychiatric component to the disease that is phenomenologically similar to obsessive-compulsive disorder (OCD) in terms of the repetitive, perseverative, and persistent nature of the symptoms. The Maudsley OCD questionnaire was administered to 21 patients with blepharospasm and 19 normal controls. The blepharospasm patients scored significantly higher than the controls (p < .01). Although preliminary, the current study does support at least a phenomenological link between OCD and blepharospasm. RP BIHARI, K (reprint author), NIMH,CLIN SCI LAB,BLDG 10,ROOM 3D41,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 20 TC 32 Z9 32 U1 1 U2 4 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 FEB PY 1992 VL 180 IS 2 BP 130 EP 132 DI 10.1097/00005053-199202000-00011 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA HD020 UT WOS:A1992HD02000011 PM 1737975 ER PT J AU BRENNEMAN, DE SCHULTZBERG, M BARTFAI, T GOZES, I AF BRENNEMAN, DE SCHULTZBERG, M BARTFAI, T GOZES, I TI CYTOKINE REGULATION OF NEURONAL SURVIVAL SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE INTERLEUKIN-1; CELL CULTURES; DEVELOPMENT; SPINAL CORD; TROPHIC FACTORS; GLIA ID VASOACTIVE-INTESTINAL-PEPTIDE; CORTICOTROPIN-RELEASING-FACTOR; SPINAL-CORD CULTURES; CENTRAL-NERVOUS-SYSTEM; INTERLEUKIN-1 PRECURSOR; ELECTRICAL-ACTIVITY; NEUROTROPHIC ACTION; MOLECULAR-BIOLOGY; ACTIVATING FACTOR; T-CELLS AB Interleukin-1 is a cytokine involved in the immune response to infection and inflammation as well as a growth promotor for several cell types. Interleukin-1-like immunoreactive material has been found in the nervous system. We now show that antisera, which blocked the T-cell proliferative effects of interleukin-1-alpha, decreased neuronal cell counts (to 40% of control) in dissociated spinal cord cultures derived from fetal mice. This neuronal loss was prevented by addition of interleukin-1-alpha, and to a lesser extent by interleukin-1-beta. Exogenous interleukin-1-alpha increased the survival of neurons when added to cultures in which the electrical activity was blocked with tetrodotoxin, whereas no such cytokine-related increase in neuronal survival was observed in electrically active cultures. The antiserum-induced death could also be prevented by cotreatment of the cultures with 0.1 nM vasoactive intestinal peptide, a substance that induces the secretion of neuronal trophic factors from nonneuronal spinal cord cells and thereby increases neuronal survival in electrically inactive cultures. These studies indicate that the cytokine interleukin-1, or an immunologically cross-reactive protein, can increase neuronal survival. C1 NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. UNIV STOCKHOLM,ARRHENIUS LAB,DEPT BIOCHEM,S-10691 STOCKHOLM,SWEDEN. RP BRENNEMAN, DE (reprint author), NICHHD,DEV NEUROBIOL LAB,NEUROCHEM UNIT,BLDG 36,ROOM 2A21,BETHESDA,MD 20892, USA. RI Schultzberg, Marianne/E-7076-2014 OI Schultzberg, Marianne/0000-0002-8314-0927 NR 54 TC 196 Z9 197 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 FEB PY 1992 VL 58 IS 2 BP 454 EP 460 DI 10.1111/j.1471-4159.1992.tb09743.x PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA HA107 UT WOS:A1992HA10700008 PM 1729393 ER PT J AU GRINO, M BURGUNDER, JM AF GRINO, M BURGUNDER, JM TI ONTOGENY OF EXPRESSION AND GLUCOCORTICOID REGULATION OF THE ARGININE VASOPRESSIN GENE IN THE RAT HYPOTHALAMIC PARAVENTRICULAR NUCLEUS SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE ARGININE VASOPRESSIN; INSITU HYBRIDIZATION; PARAVENTRICULAR NUCLEUS; GLUCOCORTICOIDS; DEVELOPMENT ID CORTICOTROPIN-RELEASING-FACTOR; HYPOPHYSEAL PORTAL BLOOD; INSULIN-INDUCED HYPOGLYCEMIA; MESSENGER-RNA; INSITU HYBRIDIZATION; UNRESTRAINED RAMS; STRESS RESPONSE; MEDIAN-EMINENCE; FACTOR CRF; PITUITARY AB Corticotropin-releasing factor and arginine vasopressin (AVP) are the two major hypothalamic factors that regulate anterior pituitary adrenocorticotropin secretion during stress. We have previously reported that the expression of the corticotropin-releasing factor gene in the hypothalamus and its regulation by glucocorticoids were not mature during the first week of life in the rat, i.e. during the stress non-responsive period. In this report, we studied the ontogeny of expression of the AVP gene in the hypothalamic paraventricular nucleus in rats using in situ hybridization. AVP mRNA was detected as early as day 20 of gestation (E20) both in the parvocellular and the magnocellular portion of the paraventricular nucleus. The levels of expression of the AVP gene increased steadily from E20 to the third day after birth (P3) and remained stable from P3 to P14. Bilateral surgical adrenalectomy induced an increase in AVP mRNA levels in the parvocellular portion of the paraventricular nucleus, but not in the magnocellular portion, in both 7-day-old and 14-day-old rats, suggesting that the glucocorticoid regulation of the AVP synthesizing neurons of the paraventricular nucleus is mature in the developing postnatal rat. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. INSERM,U297,NEUROENDOCRINOL EXPTL LAB,F-13326 MARSEILLE,FRANCE. UNIV BERN,INSELSPITAL,NEUROL KLIN & POLIKLIN,NEUROMORPHOL LAB,CH-3010 BERN,SWITZERLAND. NR 35 TC 13 Z9 13 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD FEB PY 1992 VL 4 IS 1 BP 71 EP 77 DI 10.1111/j.1365-2826.1992.tb00348.x PG 7 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA HD561 UT WOS:A1992HD56100012 PM 21554580 ER PT J AU DACUNHA, A VITKOVIC, L AF DACUNHA, A VITKOVIC, L TI TRANSFORMING GROWTH FACTOR-BETA-1 (TGF-BETA-1) EXPRESSION AND REGULATION IN RAT CORTICAL ASTROCYTES SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE TRANSFORMING GROWTH FACTOR-BETA-1; ASTROCYTE; INTERLEUKIN-1 ID TUMOR NECROSIS FACTOR; CENTRAL NERVOUS-SYSTEM; FIBRILLARY ACIDIC PROTEIN; FACTOR-BETA; MESSENGER-RNA; FACTOR-ALPHA; DEVELOPMENTAL EXPRESSION; CULTURED ASTROCYTES; ASTROGLIAL CELLS; DEVELOPING BRAIN AB Transforming growth factor-beta 1 (TGF-beta 1) is a potent modulator of immune and gilal cells functions and thus, could play an important role in neuro-immune interaction. However, published reports disagree on whether or not TGF-beta-1 is expressed in normal brain. We demonstrate here the constitutive expression of TGF-beta-1 mRNA but not protein in both cerebral cortex and primary rat cortical astrocytes. Steady-state TGF-beta-1 mRNA level increased 2-fold in adult compared to neonatal cortex and during proliferation and differentiation of astrocytes in primary culture. This response was not accompanied by the appearance of detectable TGF-beta protein either in vivo or in vitro. However, both intracellular immunoreactive TGF-beta and extracellular TGF-beta-1 activity were detected upon in vitro stimulation of astrocytes with interleukin-1 (IL-1). The extracellular TGF-beta-1 increased with time of exposure to and concentration of IL-1. In contrast, the amount of TGF-beta-1 mRNA remained unchanged during stimulation of astrocytes with IL-1. These results suggest that the production of TGF-beta-1 in astrocytes is regulated at both mRNA and protein levels. The former may occur during astrocytic development, and the latter during astrocytic response to injury in association with elevation of IL-1. C1 NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM 11B-13,BETHESDA,MD 20892. NR 52 TC 95 Z9 98 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD FEB PY 1992 VL 36 IS 2-3 BP 157 EP 169 PG 13 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA HB734 UT WOS:A1992HB73400008 PM 1732279 ER PT J AU RAO, SM DEVINSKY, O GRAFMAN, J STEIN, M USMAN, M UHDE, TW THEODORE, WH AF RAO, SM DEVINSKY, O GRAFMAN, J STEIN, M USMAN, M UHDE, TW THEODORE, WH TI VISCOSITY AND SOCIAL COHESION IN TEMPORAL-LOBE EPILEPSY SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID INTERICTAL BEHAVIOR; INVENTORY; LESIONS AB Clinical case reports suggest that viscosity, the behavioural tendency to talk repetitively and circumstantially about a restricted range of topics, is common in patients with temporal lobe epilepsy (TLE). Such patients are also reported to exhibit heightened levels of social cohesion, the tendency to become interpersonally "clingy". This "sticky" interpersonal style may be particularly common in TLE patients with a left sided temporal lobe seizure focus. To test this hypothesis, self-report and observer rating scales were developed to assess both viscosity and social cohesion. Subjects consisted of patients with right, left, or bilateral temporal lobe seizure foci, absence or primary generalised tonic-clonic seizures, psychiatric controls (panic disorder patients), and normal controls. Elevations on the viscosity scale were observed primarily in TLE patients with left or bilateral seizure foci. Viscosity scores also correlated with seizure duration and left handedness. No group differences were observed on the social cohesion scale. These findings are consistent with the hypothesis that viscosity results from subtle interictal language disturbances, although other pathogenetic mechanisms are discussed. C1 NYU,HOSP JOINT DIS,SCH MED,DEPT NEUROL,NEW YORK,NY 10003. NINCDS,MED NEUROL BRANCH,BETHESDA,MD 20892. NIMH,BIOL PSYCHIAT BRANCH,COGNIT NEUROSCI SECT,BETHESDA,MD 20892. NIMH,BIOL PSYCHIAT BRANCH,CLIN EPILEPSY SECT,BETHESDA,MD 20892. NIMH,BIOL PSYCHIAT BRANCH,ANXIETY & AFFECT DISORDERS SECT,BETHESDA,MD 20892. ALLEGHENY GEN HOSP,DEPT MED,PITTSBURGH,PA 15212. RP RAO, SM (reprint author), MED COLL WISCONSIN,DEPT NEUROL,NEUROPSYCHOL SECT,9200 W WISCONSIN AVE,MILWAUKEE,WI 53226, USA. RI Rao, Stephen/A-2460-2010; OI Rao, Stephen/0000-0002-6463-7460; Grafman, Jordan H./0000-0001-8645-4457 NR 22 TC 10 Z9 10 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD FEB PY 1992 VL 55 IS 2 BP 149 EP 152 DI 10.1136/jnnp.55.2.149 PG 4 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA HD380 UT WOS:A1992HD38000016 PM 1538223 ER PT J AU PATNEAU, DK MAYER, ML JANE, DE WATKINS, JC AF PATNEAU, DK MAYER, ML JANE, DE WATKINS, JC TI ACTIVATION AND DESENSITIZATION OF AMPA KAINATE RECEPTORS BY NOVEL DERIVATIVES OF WILLARDIINE SO JOURNAL OF NEUROSCIENCE LA English DT Article ID AMINO-ACID RECEPTORS; SELECTIVE GLUTAMATE RECEPTORS; CULTURED HIPPOCAMPAL-NEURONS; QUISQUALATE RECEPTORS; XENOPUS OOCYTES; RAT; MODULATION; CHANNELS; BLOCKADE; GLYCINE AB Willardine [(S)-1-(2-amino-2-carboxyethyl)pyrimidine-2,4-dione] is a naturally occurring heterocyclic excitatory amino acid present in the seeds of Acacia and Mimosa. A series of 5-substituted willardiines were synthesized in single en-antiomeric forms and tested for activity at AMPA/kainate receptors, using whole-cell recording from mouse embryonic hippocampal neurons. The (S)- but not (R)-isomers of willardine and 5-bromowillardiine were potent agonists, producing rapidly but incompletely desensitizing responses. At equilibrium, (S)-5-fluorowillardiine (EC50, 1.5-mu-M) was seven times more potent than (R,S)-AMPA (EC50, 11-mu-M) and 30 times more potent than willardiine (EC50, 45-mu-M); the potency sequence was fluoro > nitro > chloro almost-equal-to bromo > iodo > willardiine. Willardiines produce strikingly different degrees of desensitization: at saturating doses the equilibrium response to the weakly desensitizing agonist (S)-5-iodowillardiine was similar in amplitude to the response to kainate and 10 times larger than the response to the strongly desensitizing agonist (S)-willardiine. The desensitization sequence was fluoro > willardiine > nitro almost-equal-to chloro > bromo > iodo > kainate. Cross-desensitization experiments confirm that willardiines bind to the same receptors activated by kainate and AMPA, and show that both the rapidly desensitizing and equilibrium responses to willardiines are mediated by the same receptor: (S)-5-iodowillardiine blocked activation of the rapidly desensitizing response evoked by (S)-willardiine and (S)-5-fluorowillardiine, while the latter agonists blocked the equilibrium response to (S)-5-iodowillardiine. A slowly decaying inward tail current was recorded after a brief application of (S)-5-fluorowillardiine but not (S)-willardiine, consistent with a model in which willardiines bind with different affinity to desensitized receptors, such that following removal of agonist, receptors trapped in the desensitized state can return to the open state before dissociation of agonist terminates receptor activation. Willardiines are the first compounds characterized in which simple changes in molecular structure are associated with marked differences in the ability of agonists to produce desensitization of AMPA/kainate receptors. C1 NICHHD,DEV NEUROBIOL LAB,NEUROPHYSIOL & BIOPHYS SECT,BLDG 36,ROOM 2A21,BETHESDA,MD 20892. UNIV BRISTOL,SCH MED SCI,DEPT PHARMACOL,BRISTOL BS8 1TD,AVON,ENGLAND. RI Mayer, Mark/H-5500-2013 NR 38 TC 94 Z9 95 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD FEB PY 1992 VL 12 IS 2 BP 595 EP 606 PG 12 WC Neurosciences SC Neurosciences & Neurology GA HE710 UT WOS:A1992HE71000020 PM 1371315 ER PT J AU MESCO, ER JOSEPH, JA ROTH, GS AF MESCO, ER JOSEPH, JA ROTH, GS TI SELECTIVE SUSCEPTIBILITY OF CULTURED STRIATAL NEURONS TO KAINIC ACID SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE DOPAMINE; D2-RECEPTORS; EXCITOTOXICITY; STRIATUM ID RAT STRIATUM; ALZHEIMERS-DISEASE; DOPAMINE-RECEPTORS; AGE; ONTOGENY; BINDING; BRAIN AB Previous work has shown a selective sensitivity of striatal D2-receptor-containing neurons (D2 cells) to kainic acid (KA). In order to see whether this phenomenon exists in cultured cells, which could provide a very accessible model for subsequent mechanistic studies, we examined striatal cultures grown for up to 30 days and labeled with either [H-3]spiperone, for D2 receptors, or with [H-3]-SCH23390, for D1 receptors. Analysis of the cells was performed with a digital imaging system (RAS). The cultured cells were examined for ligand binding to receptors, cell size, and susceptibility to KA. The D2 cells showed an increased mortality over D1-receptor-containing neurons (D1 cells) in the presence of KA, of a magnitude similar to in vivo loss, with larger D2 cells showing the greatest vulnerability. RP MESCO, ER (reprint author), NIA,GERONTOL RES CTR,BALTIMORE,MD 21224, USA. NR 25 TC 18 Z9 18 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 FEB PY 1992 VL 31 IS 2 BP 341 EP 345 DI 10.1002/jnr.490310216 PG 5 WC Neurosciences SC Neurosciences & Neurology GA HD578 UT WOS:A1992HD57800015 PM 1533426 ER PT J AU FRALIC, MF AF FRALIC, MF TI NURSE EXECUTIVE PRACTICE - INTO THE NEXT MILLENNIUM - FROM LIMBO DANCER TO POLE VAULTER SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article AB Nurse executives, administrators, and managers are constantly being challenged by the changes in healthcare. Although it sometimes seems there is really nothing new, proactive visionary nurse administrators can rediscover, redesign, and redirect their own and others' activities to achieve organizational effectiveness. Such approaches require periodic examination of all strategies and practices-past, present, and future-for their relevance, practicality, and success. The editors of "Executive Development" reflect on topics important to organizational life. C1 RUTGERS STATE UNIV,COLL NURSING,NEW BRUNSWICK,NJ 08903. NIH,NATL ADVISORY COUNCIL NURSING RES,BETHESDA,MD 20892. RP FRALIC, MF (reprint author), ROBERT WOOD JOHNSON FDN,NURSING,PRINCETON,NJ 08540, USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD FEB PY 1992 VL 22 IS 2 BP 15 EP 16 DI 10.1097/00005110-199202000-00019 PG 2 WC Nursing SC Nursing GA HD042 UT WOS:A1992HD04200006 PM 1735799 ER PT J AU KOHN, WG SHIP, JA ATKINSON, JC PATTON, LL FOX, PC AF KOHN, WG SHIP, JA ATKINSON, JC PATTON, LL FOX, PC TI SALIVARY-GLAND TC-99M-SCINTIGRAPHY - A GRADING SCALE AND CORRELATION WITH MAJOR SALIVARY-GLAND FLOW-RATES SO JOURNAL OF ORAL PATHOLOGY & MEDICINE LA English DT Article DE PAROTID GLAND; RATING SCALE; SALIVA; SALIVARY FLOW RATES; SEQUENTIAL SALIVARY SCINTIGRAPHY; SUBMANDIBULAR GLAND; TECHNETIUM PERTECHNETATE ID SJOGRENS SYNDROME; SCINTIGRAPHY; XEROSTOMIA; AGE AB Sequential salivary gland scintigraphy with Tc-99m-technetium pertechnetate (Tc-99) is a safe, minimally invasive test for study of major salivary glands. However, its relationship to salivary function has not been investigated in detail. We have investigated the relationship between major salivary gland flow rates and Tc-99 scans and developed a new rating scale using scans of a control group with normal salivary function. Salivary flow rates and Tc-99 scans were obtained from healthy, non-medicated subjects (n = 33) and from xerostomic patients (n = 22). There were significant differences between the groups for salivary flow rates and Tc-99 ratings. Significant correlations were found between salivary flow rates and Tc-99 ratings in the control and xerostomic groups. The Tc-99 rating scale proved reliable in assessing salivary dysfunction, and showed a high inter-examiner correlation. These results demonstrate the usefulness of salivary gland scintigraphy in assessing major salivary gland flow rates and the utility of a new rating scale. RP KOHN, WG (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,9000 ROCKVILLE PIKE,BLDG 10,BETHESDA,MD 20892, USA. NR 19 TC 60 Z9 60 U1 2 U2 5 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0904-2512 J9 J ORAL PATHOL MED JI J. Oral Pathol. Med. PD FEB PY 1992 VL 21 IS 2 BP 70 EP 74 DI 10.1111/j.1600-0714.1992.tb00982.x PG 5 WC Dentistry, Oral Surgery & Medicine; Pathology SC Dentistry, Oral Surgery & Medicine; Pathology GA HH068 UT WOS:A1992HH06800004 PM 1313502 ER PT J AU BARTON, NW BRADY, RO DAMBROSIA, JM DOPPELT, SH HILL, SC HOLDER, CA MANKIN, HJ MURRAY, GJ ZIRZOW, GC PARKER, RI AF BARTON, NW BRADY, RO DAMBROSIA, JM DOPPELT, SH HILL, SC HOLDER, CA MANKIN, HJ MURRAY, GJ ZIRZOW, GC PARKER, RI TI DOSE-DEPENDENT RESPONSES TO MACROPHAGE-TARGETED GLUCOCEREBROSIDASE IN A CHILD WITH GAUCHER DISEASE SO JOURNAL OF PEDIATRICS LA English DT Note ID INHERITED ENZYME DEFICIENCY; PURIFIED GLUCOCEREBROSIDASE; REPLACEMENT THERAPY AB Long-term studies of a child with Gaucher disease indicated that the response to treatment with macrophage-targeted glucocerebrosidase (glucosylceramidase) is dose dependent, and that the hematologic response precedes the skeletal response. C1 NINCDS, BIOMETRY & FIELD STUDIES BRANCH, BETHESDA, MD 20892 USA. NIH, DEPT DIAGNOST RADIOL, BETHESDA, MD 20892 USA. NIH, CTR CLIN, DEPT CLIN PATHOL, BETHESDA, MD 20892 USA. MASSACHUSETTS GEN HOSP, DEPT ORTHOPED SURG, BOSTON, MA 02114 USA. RP BARTON, NW (reprint author), NINCDS, DEV & METAB NEUROL BRANCH, BETHESDA, MD 20892 USA. NR 12 TC 55 Z9 56 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 FEB PY 1992 VL 120 IS 2 BP 277 EP 280 DI 10.1016/S0022-3476(05)80444-5 PN 1 PG 4 WC Pediatrics SC Pediatrics GA HC901 UT WOS:A1992HC90100023 PM 1735829 ER PT J AU PIEDMONT, RL MCCRAE, RR COSTA, PT AF PIEDMONT, RL MCCRAE, RR COSTA, PT TI AN ASSESSMENT OF THE EDWARDS PERSONAL PREFERENCE SCHEDULE FROM THE PERSPECTIVE OF THE 5-FACTOR MODEL SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID SOCIAL DESIRABILITY; DIMENSIONS; SCALES AB We examined the validity of need scales of the Edwards Personal Preference Schedule (EPPS) by correlating them with a measure of the five basic factors of personality; we also considered test format as a possible source of invalidity. Three hundred thirty (223 women, 107 men) undergraduate students completed both the NEO Personality Inventory (NEO-PI)-a measure of the five factors-and one of two versions of the EPPS. Results show that both ipsative and normative versions of the EPPS could be meaningfully interpreted within the five-factor model, although the ipsative, forced-choice format of the standard EPPS apparently lowered validity coefficients and decreased convergent and discriminant validity. We argue that the five-factor model can provide a useful interpretive context for evaluating many clinical measures. C1 NIA,GERONTOL RES CTR,PERSONAL & COGNIT,4940 EASTERN AVE,BALTIMORE,MD 21224. OI Costa, Paul/0000-0003-4375-1712 NR 41 TC 43 Z9 43 U1 2 U2 16 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD FEB PY 1992 VL 58 IS 1 BP 67 EP 78 DI 10.1207/s15327752jpa5801_6 PG 12 WC Psychology, Clinical; Psychology, Social SC Psychology GA HB046 UT WOS:A1992HB04600006 PM 1545345 ER PT J AU KING, FG DEDRICK, RL AF KING, FG DEDRICK, RL TI PHYSIOLOGICAL PHARMACOKINETIC PARAMETERS FOR CIS-DICHLORODIAMMINEPLATINUM(II) (DDP) IN THE MOUSE SO JOURNAL OF PHARMACOKINETICS AND BIOPHARMACEUTICS LA English DT Article DE PHARMACOKINETICS; PHYSIOLOGICAL MODEL; CISPLATIN; DDP; CIS-DICHLORODIAMMINE-PLATINUM(II) ID MODEL; MICE; CARBOPLATIN; CISPLATIN C1 NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BLDG 13,BETHESDA,MD 20892. N CAROLINA AGR & TECHNOL STATE UNIV,DEPT CHEM ENGN,GREENSBORO,NC 27411. NR 9 TC 12 Z9 12 U1 2 U2 4 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0090-466X J9 J PHARMACOKINET BIOP JI J. Pharmacokinet. Biopharm. PD FEB PY 1992 VL 20 IS 1 BP 95 EP 99 DI 10.1007/BF01143187 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HL074 UT WOS:A1992HL07400004 PM 1588505 ER PT J AU KIRCH, DG TAYLOR, TR CREESE, I XU, SX WYATT, RJ AF KIRCH, DG TAYLOR, TR CREESE, I XU, SX WYATT, RJ TI EFFECT OF CHRONIC NICOTINE TREATMENT AND WITHDRAWAL ON RAT STRIATAL D1 AND D2 DOPAMINE-RECEPTORS SO JOURNAL OF PHARMACY AND PHARMACOLOGY LA English DT Article ID TARDIVE-DYSKINESIA; PARKINSONS-DISEASE; SMOKING; BRAIN; INCREASE; BINDING; RELEASE; SYSTEM; DRUGS; MICE AB The effects on rat striatal dopamine receptors after chronic nicotine administration (3 and 12mg kg-1 day-1), and after withdrawal from chronic nicotine (12 mg kg-1 day-1), were studied. After 21 days of continuous minipump infusion, the control (saline) and nicotine-treated rats were killed. The nicotine-withdrawal rats were killed on day 28, 7 days after pump removal: Radioligand studies were performed to determine D1 ([H-3]SCH23390) and D2 ([H-3]spiperone) striatal dopamine receptor affinity (K(d)) and maximum binding (B(max)). Dopamine inhibition of antagonist binding at 3 concentrations and the effect of 0.3 mM GTP on binding affinity were examined. No statistically significant differences between control and nicotine treatment or withdrawal groups were noted in either D1 or D2 receptor K(d) or B(max). Although nicotine has been shown to affect nigrostriatal dopamine release, chronic treatment does not appear to alter overall striatal dopaminergic receptor binding parameters. C1 NIMH,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. RUTGERS STATE UNIV,CTR MOLEC & BEHAV NEUROSCI,NEWARK,NJ 07102. NIMH,NEUROPSYCHIAT BRANCH,ROCKVILLE,MD 20857. NIMH,DIV CLIN RES,WASHINGTON,DC 20032. RP KIRCH, DG (reprint author), NIMH,DIV CLIN RES,5600 FISHERS LANE,ROOM 10-105,ROCKVILLE,MD 20857, USA. FU NIDA NIH HHS [DA 04612]; NIMH NIH HHS [MH 32990] NR 26 TC 22 Z9 22 U1 0 U2 0 PU ROYAL PHARMACEUTICAL SOC GREAT BRITAIN PI LONDON PA 1 LAMBETH HIGH ST, LONDON, ENGLAND SE1 7JN SN 0022-3573 J9 J PHARM PHARMACOL JI J. Pharm. Pharmacol. PD FEB PY 1992 VL 44 IS 2 BP 89 EP 92 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HE484 UT WOS:A1992HE48400004 PM 1352822 ER PT J AU LUSSO, P GALLO, RC AF LUSSO, P GALLO, RC TI PATHOGENESIS OF AIDS SO JOURNAL OF PHARMACY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT BRITISH PHARMACEUTICAL CONF : IMPACT OF THE NEW BIOLOGIES ON THE MEDICAL AND PHARMACEUTICAL SCIENCES CY SEP 10-13, 1991 CL MERSEYSIDE, ENGLAND SP ROYAL PHARM SOC ID IMMUNODEFICIENCY-VIRUS TYPE-1; LONG-TERM CULTURE; KAPOSIS-SARCOMA; HTLV-III; T-CELL; ENVELOPE PROTEIN; HIV-INFECTION; LYMPHOCYTES; GROWTH; GLYCOPROTEIN C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NR 33 TC 3 Z9 3 U1 0 U2 0 PU ROYAL PHARMACEUTICAL SOC GREAT BRITAIN PI LONDON PA 1 LAMBETH HIGH ST, LONDON, ENGLAND SE1 7JN SN 0022-3573 J9 J PHARM PHARMACOL JI J. Pharm. Pharmacol. PD FEB PY 1992 VL 44 SU 1 BP 160 EP 164 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HF080 UT WOS:A1992HF08000003 PM 1348277 ER PT J AU SPURGEON, HA DUBELL, WH STERN, MD SOLLOTT, SJ ZIMAN, BD SILVERMAN, HS CAPOGROSSI, MC TALO, A LAKATTA, EG AF SPURGEON, HA DUBELL, WH STERN, MD SOLLOTT, SJ ZIMAN, BD SILVERMAN, HS CAPOGROSSI, MC TALO, A LAKATTA, EG TI CYTOSOLIC CALCIUM AND MYOFILAMENTS IN SINGLE-RAT CARDIAC MYOCYTES ACHIEVE A DYNAMIC EQUILIBRIUM DURING TWITCH RELAXATION SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID INTRACELLULAR CA-2+ TRANSIENT; SARCOPLASMIC-RETICULUM; VENTRICULAR MUSCLE; PURKINJE-FIBERS; CONTRACTION; CELLS; HEART; PH; CAFFEINE; FORCE AB 1. Single isolated rat cardiac myocytes were loaded with either the pentapotassium salt form or the acetoxymethyl ester (AM) form of the calcium-sensitive fluorescent probe, Indo-1. The relationship of the Indo-1 fluorescence transient, an index of the change in cytosolic calcium [Ca2+]i concentration, to the simultaneously measured cell length during the electrically stimulated twitch originating from slack length at 23-degrees-C was evaluated. It was demonstrated that even if the Ca2+ dissociation rate from Indo-1 was assumed to be as slow as 10 s-1, the descending limb ('relaxation phase') of the Indo-1 fluorescence transient induced by excitation under these conditions is in equilibrium with the [Ca2+]i transient. Additionally, the extent of Indo-1 loading employed did not substantially alter the twitch characteristics. 2. A unique relationship between the fluorescence transient and cell length was observed during relaxation of contractions that varied in amplitude. This was manifest as a common trajectory in the cell length vs. [Ca2+]i phase-plane diagrams beginning at the time of cell relengthening. The common trajectory could also be demonstrated in Indo-1 AM-loaded cells. The Indo-1 fluorescence-length relation defined by this common trajectory is steeper than that described by the relation of peak contraction amplitude and peak fluorescence during the twitch contractions. 3. The trajectory of the [Ca2+]i-length relation elicited via an abrupt, rapid, brief (200 ms) pulse of caffeine directly onto the cell surface or by 'tetanization' of cells in the presence of ryanodine is identical to the common [Ca2+]i-length trajectory formed by electrically stimulated contractions of different magnitudes. As the [Ca2+]i and lentth transients induced by caffeine application or during tetanization in the presence of ryanodine develop with a much slower time course than those elicited by electrical stimulation, the common trajectory is not fortuitous, i.e. it cannot be attributed to equivalent rate-limiting steps for the decrease of [Ca2+]i and cell relengthening. 4. The [Ca2+]i-length relation defined by the common trajectory shifts appropriately in response to perturbations that have previously been demonstrated to alter the steady-state myofilament Ca2+ sensitivity in skinned cardiac fibres. Specifically, the trajectory shifts leftward in response to an acute increase in pH or following the addition of novel myofilament calcium-sensitizing thiadiazinone derivatives; a rightward shift occurs in response to an acute reduction in pH or following the addition of butanedione monoxime. Each of these perturbations markedly shifted the trajectory in the absence of changes in the amplitude of the [Ca2+]i transient. 5. We conclude that the [Ca2+]i-cell length trajectory during the relaxation phase of the twitch contraction in single cardiac myocytes defines a quasi-equilibrium of cytosolic [Ca2+] myofilament Ca2+ binding and mechanical force and thus cell length. The occurrence of this trajectory indicates that the [Ca2+]i decay is a factor that governs relaxation of twitch contraction. Additionally, the position of this trajectory reflects the relative myofilament response to Ca2+. C1 JOHNS HOPKINS MED INST,DIV CARDIOL,BALTIMORE,MD 21205. RP SPURGEON, HA (reprint author), NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224, USA. NR 44 TC 109 Z9 109 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD FEB PY 1992 VL 447 BP 83 EP 102 PG 20 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA HE201 UT WOS:A1992HE20100006 PM 1593465 ER PT J AU ROBERTS, WC KISHEL, JC MCINTOSH, CL CANNON, RO MARON, BJ AF ROBERTS, WC KISHEL, JC MCINTOSH, CL CANNON, RO MARON, BJ TI SEVERE MITRAL OR AORTIC-VALVE REGURGITATION, OR BOTH, REQUIRING VALVE-REPLACEMENT FOR INFECTIVE ENDOCARDITIS COMPLICATING HYPERTROPHIC CARDIOMYOPATHY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID OBSTRUCTIVE CARDIOMYOPATHY; STENOSIS AB Certain clinical and morphologic findings are described in 11 patients with hypertrophic cardiomyopathy complicated by infective endocarditis that produced severe mitral or aortic valve regurgitation, or both, necessitating valve replacement. All 11 patients had changes in the operatively excised valve or valves characteristic of healed infective endocarditis. The infection involved only the mitral valve in seven patients, only the aortic valve in three patients and both valves in one patient. Study of the operatively excised mitral valves indicated that the healed vegetations were located most commonly on the left ventricular aspects of the anterior mitral leaflet, indicating that vegetation had formed at contact points of this leaflet with moral endocardium of the left ventricular outflow tract. In all 11 patients, the infective endocarditis either worsened preexisting valve regurgitation or initiated valve regurgitation and led to worsened signs and symptoms of cardiac dysfunction, necessitating valve replacement. Functional class improved in the nine patients who survived 7 to 101 months after valve replacement. Hypertrophic cardiomyopathy appears to be a factor predisposing to infective endocarditis. Patients with hypertrophic cardiomyopathy should receive prophylactic antibiotic therapy during procedures that predispose to infective endocarditis. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NHLBI,SURG BRANCH,BETHESDA,MD 20892. RP ROBERTS, WC (reprint author), NHLBI,PATHOL BRANCH,BLDG 10,ROOM 2N258,BETHESDA,MD 20892, USA. NR 12 TC 23 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1992 VL 19 IS 2 BP 365 EP 371 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA HB879 UT WOS:A1992HB87900022 PM 1732366 ER PT J AU BAUM, BJ FOX, PC AF BAUM, BJ FOX, PC TI RECOVERY OF INFECTIOUS HIV-1 FROM WHOLE SALIVA - COMMENT SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Editorial Material RP BAUM, BJ (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD FEB PY 1992 VL 123 IS 2 BP 38 EP 38 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA HE472 UT WOS:A1992HE47200012 ER PT J AU KREBSSMITH, SM CRONIN, FJ HAYTOWITZ, DB COOK, DA AF KREBSSMITH, SM CRONIN, FJ HAYTOWITZ, DB COOK, DA TI FOOD SOURCES OF ENERGY, MACRONUTRIENTS, CHOLESTEROL, AND FIBER IN DIETS OF WOMEN SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article AB Data from the 1985 Continuing Survey of Food Intakes by Individuals were used to calculate the contributions of individual foods to women's intakes of energy, protein, carbohydrate, fat, saturated fatty acids, cholesterol, and fiber. We separated nearly all food mixtures into their constituent ingredients, grouped the ingredients together with similar foods, and examined the contributions of those foods. Yeast breads that were neither whole grain nor higher fiber contributed about 7% of the energy to the diets, which made them the leading source of energy of the foods we examined. The leading sources of protein were animal products: poultry contributed approximately 12%, beef contributed about 19%, cheese contributed about 89%, and pork contributed about 6%. The various fats and oils were the greatest contributors to fat, and cheese was the chief source of saturated fatty acids. Eggs were the major source of cholesterol; they provided around 36% of the total. Two of the top three sources of carbohydrate-regular soft drinks and sugar-are composed entirely of simple sugars. Potatoes provided around 11% of the fiber, which made them the leading source of fiber. This article shows that the relative ranking of foods and the contribution of each food depend on the way food codes are combined. Therefore, citing one food as the major source of a particular food component without including documentation of how foods are combined can be misleading. C1 USDA,HUMAN NUTR INFORMAT SERV,HYATTSVILLE,MD 20782. RP KREBSSMITH, SM (reprint author), NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892, USA. NR 8 TC 33 Z9 33 U1 0 U2 1 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD FEB PY 1992 VL 92 IS 2 BP 168 EP 174 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA HC897 UT WOS:A1992HC89700010 PM 1310699 ER PT J AU POWERS, DC MURPHY, BR FRIES, LF ADLER, WH CLEMENTS, ML AF POWERS, DC MURPHY, BR FRIES, LF ADLER, WH CLEMENTS, ML TI REDUCED INFECTIVITY OF COLD-ADAPTED INFLUENZA-A H1N1 VIRUSES IN THE ELDERLY - CORRELATION WITH SERUM AND LOCAL ANTIBODIES SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID LINKED IMMUNOSORBENT-ASSAY; INACTIVATED VACCINE; YOUNG-CHILDREN; LIVE; RESPONSES; ADULTS AB Objective: To compare young and elderly adults in terms of their immune responses and rates of infection following intranasal vaccination with a live attenuated influenza virus. Design: Time series, comparing outcomes in young and elderly convenience sample. Method: Retrospective laboratory analysis of serum and nasal wash specimens collected during prior studies in which young or elderly volunteers had been inoculated with cold-adapted influenza A/Kawasaki/86 (H1N1) reassortant virus. Setting: Johns Hopkins Center for Immunization Research. Participants: Healthy young and elderly adults with prevaccination serum hemagglutination inhibition (HAI) antibody titers less-than-or-equal-to 1:8. Outcome Measurements: Antibody responses in serum and nasal washes. Main Results: The proportion of vaccinees who developed any serum or local antibody response was higher in young compared with elderly subjects (20/20 vs 5/14, P < 0.0005). Resistance to infection with cold-adapted virus correlated with pre-vaccination levels of serum immunoglobulin G (IgG), serum IgA, and nasal wash IgA antibody to whole virus antigen. Age was highly correlated with a lack of response to vaccine by simple regression, but not when data were adjusted for pre-existing antibody levels. Conclusions: Cold-adapted reassortant influenza A H1N1 viruses achieve lower rates of infection in elderly than young adults, primarily due to age-related differences in preexisting levels of immunity which may not be reflected by HAI titer. C1 ST LOUIS UNIV,DEPT MED,DIV GERIATR MED,ST LOUIS,MO 63103. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,CTR IMMUNOZAT RES,BALTIMORE,MD 21218. NIA,GERONTOL RES CTR,CLIN IMMUNOL SECT,BETHESDA,MD 20892. RP POWERS, DC (reprint author), VET ADM MED CTR,CTR GERONTOL RES EDUC & CLIN,ST LOUIS,MO 63125, USA. FU PHS HHS [N01-A1-62515] NR 27 TC 30 Z9 33 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 FEB PY 1992 VL 40 IS 2 BP 163 EP 167 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA HC685 UT WOS:A1992HC68500011 PM 1740601 ER PT J AU PERKINS, JR PARKER, CE TOMER, KB AF PERKINS, JR PARKER, CE TOMER, KB TI NANOSCALE SEPARATIONS COMBINED WITH ELECTROSPRAY IONIZATION MASS-SPECTROMETRY - SULFONAMIDE DETERMINATION SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID CAPILLARY ZONE ELECTROPHORESIS; PERFORMANCE LIQUID-CHROMATOGRAPHY; FAST-ATOM-BOMBARDMENT; AZO DYES; INTERFACE; IDENTIFICATION; METABOLITES; RESIDUES; SULFAMETHAZINE; TISSUES AB Nanoscale capillary liquid chromatography (nCLC) and capillary zone electrophoresis (CZE) have been combined with quadrupole mass spectrometry via an electrospray ionization (ESI) interface. These methodologies have been applied to the separation and determination of a variety of sulfonamides. CZE/ESI/MS is the more rapid and sensitive technique, but nCLC/ESI/MS shows promise for the analysis of dilute samples. Ultimately, the two techniques provide complementary methods of analysis. The detection limits of these techniques in the full-scan mode are in the low picomole range. Dissociation of the sulfonamides can be induced by increasing the skimmer voltage. This provides a limited means of discriminating between compounds of identical molecular weight but, more important, provides fragments that could be used to confirm the presence of analyte within a sample. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. RI Tomer, Kenneth/E-8018-2013 NR 86 TC 65 Z9 65 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD FEB PY 1992 VL 3 IS 2 BP 139 EP 149 DI 10.1016/1044-0305(92)87047-3 PG 11 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA HE510 UT WOS:A1992HE51000007 PM 24242882 ER PT J AU CRESCENZO, DG HILBERT, SL BARRICK, MK CORCORAN, PC STLOUIS, JD MESSIER, RH FERRANS, VJ WALLACE, RB HOPKINS, RA AF CRESCENZO, DG HILBERT, SL BARRICK, MK CORCORAN, PC STLOUIS, JD MESSIER, RH FERRANS, VJ WALLACE, RB HOPKINS, RA TI DONOR HEART-VALVES - ELECTRON-MICROSCOPIC AND MORPHOMETRIC ASSESSMENT OF CELLULAR INJURY INDUCED BY WARM ISCHEMIA SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 71ST ANNUAL MEETING OF THE AMERICAN ASSOC FOR THORACIC SURGERY CY MAY 06-08, 1991 CL WASHINGTON, DC SP AMER ASSOC THORAC SURG ID TERM FOLLOW-UP; FROZEN AORTIC HOMOGRAFTS; REPLACEMENT; ALLOGRAFT; VIABILITY; FREEHAND; POSITION; BANK AB Cryopreserved allograft valves are increasingly being used as valvular replacements. Leaflet fibroblast viability has been suggested to influence clinical durability. The warm ischemic time is thought to be a critical determinant of this cell viability. The purpose of this study was to apply quantitative morphometric methods to characterize, by transmission electron microscopy, valvular cellular injury resulting from progressive warm ischemic time. Porcine aortic valves were harvested with a spectrum of warm ischemic times (40 minutes and 2, 6, 12, 24, and 36 hours; five valves per warm ischemic time; n = 30) and processed by standard electron microscopic methods. To ensure randomized tissue selection within each warm ischemic time interval, we randomly selected one thin section from each leaflet. The first ten cells in each thin section were photographed and cellular injury was assessed (cell disruption, dilation of endoplasmic reticulum, cytoplasmic edema, nuclear and mitochondrial changes). Nine hundred micrographs have been analyzed by Cochran-Mantel-Haenszel statistics to determine if a significant association between warm ischemic time and cellular injury exists. Our findings indicate a significant association between reversible cell injury through 24 hours of warm ischemic injury (p < 0.0001). Furthermore, a significant association between irreversible cell injury and progressive warm ischemia through 36 hours was also found. These findings indicate that the ischemic interval after donor death is associated with progressive leaflet cell injury. Cellular damage begins shortly after donor death and continues incrementally throughout 36 hours. After 2 hours of warm ischemic injury 37% of the cells had morphologic evidence of injury. After 6 hours of warm ischemic injury the number of injured cells increased to 73%. By 36 hours 22% of the cells appeared normal. Irreversible cell injury increases with prolonged ischemia and becomes quantitatively impressive at 24 hours, by which time 26% of cells are so affected. Conversely, some cells are resistant to irreversible injury for a prolonged ischemic interval. C1 GEORGETOWN UNIV,MED CTR,DEPT SURG,3800 RESERVOIR RD NW,WASHINGTON,DC 20007. US FDA,CTR DEVICES & RADIOL HLTH,OFF SCI & TECHNOL,ROCKVILLE,MD 20857. NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. NR 20 TC 29 Z9 29 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD FEB PY 1992 VL 103 IS 2 BP 253 EP 258 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA HD225 UT WOS:A1992HD22500009 PM 1735990 ER PT J AU KONINGS, DAM NASH, MA MAIZEL, JV ARLINGHAUS, RB AF KONINGS, DAM NASH, MA MAIZEL, JV ARLINGHAUS, RB TI NOVEL GACG-HAIRPIN PAIR MOTIF IN THE 5' UNTRANSLATED REGION OF TYPE-C RETROVIRUSES RELATED TO MURINE LEUKEMIA-VIRUS SO JOURNAL OF VIROLOGY LA English DT Article ID RNA SECONDARY STRUCTURE; TARGET SEQUENCE; PROTEIN; MUTANTS; HIV-1; ENCAPSIDATION; ELEMENTS; REX AB We searched for the presence of common RNA structural motifs in mammalian type C retroviruses related to murine leukemia viruses and the closely related avian spleen necrosis virus. A novel motif consisting of a pair of hairpins, called hairpin pair motif, was detected in the 5' untranslated regions of the genomes of these retroviruses. A combination of computational analyses that included the assessment of phylogenetic sequence conservation by multiple alignment, the search for regions with unusual RNA folding properties, and the analysis of RNA secondary structure by suboptimal free-energy calculations highlighted the significance of this hairpin pair motif. The hairpin pair motif encompasses 70 to 80 nucleotides between the splice donor site and the gag translational initiation codon of these viruses. The motif is composed of two adjacent hairpins both with a perfectly conserved GACG tetraloop. We propose that the novel GACG-hairpin pair motif described here constitutes an essential component of the regulatory machinery in these type C retroviruses. C1 UNIV COLORADO,BOULDER,CO 80309. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT MOLEC PATHOL,HOUSTON,TX 77030. RP KONINGS, DAM (reprint author), NCI,DIV CANC BIOL & DIAGN,MATH BIOL LAB,FREDERICK,MD 21702, USA. NR 26 TC 61 Z9 61 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1992 VL 66 IS 2 BP 632 EP 640 PG 9 WC Virology SC Virology GA GY965 UT WOS:A1992GY96500003 PM 1309906 ER PT J AU EMERSON, SU HUANG, YK MCRILL, C LEWIS, M PURCELL, RH AF EMERSON, SU HUANG, YK MCRILL, C LEWIS, M PURCELL, RH TI MUTATIONS IN BOTH THE 2B-GENE AND 2C-GENE OF HEPATITIS-A VIRUS ARE INVOLVED IN ADAPTATION TO GROWTH IN CELL-CULTURE SO JOURNAL OF VIROLOGY LA English DT Article ID COMPLETE NUCLEOTIDE-SEQUENCE; VIRAL-PROTEINS; RNA; ORGANIZATION; REPLICATION; ANTIGEN; MUTANTS; REGION AB Oligonucleotide-directed mutagenesis of an infectious cDNA clone of wild-type hepatitis A virus was performed to determine which mutations acquired in the nonstructural 2B and 2C genes during adaptation to growth in cell culture were effective in enhancing virus growth in vitro. Results of transfection assays demonstrated that one mutation in the 2B gene and two mutations in the 2C gene were responsible for an increased efficiency in growth, but growth enhancement required the participation of at least two of the three mutations. RP EMERSON, SU (reprint author), NIAID,ZENTRUM INFECT DIS,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892, USA. NR 18 TC 58 Z9 62 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1992 VL 66 IS 2 BP 650 EP 654 PG 5 WC Virology SC Virology GA GY965 UT WOS:A1992GY96500005 PM 1309907 ER PT J AU WILLEMS, L KETTMANN, R CHEN, G PORTETELLE, D BURNY, A DERSE, D AF WILLEMS, L KETTMANN, R CHEN, G PORTETELLE, D BURNY, A DERSE, D TI A CYCLIC AMP-RESPONSIVE DNA-BINDING PROTEIN (CREB2) IS A CELLULAR TRANSACTIVATOR OF THE BOVINE LEUKEMIA-VIRUS LONG TERMINAL REPEAT SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSCRIPTION FACTOR ATF; NUCLEAR FACTOR CREB; TRANS-ACTIVATOR; GENE-TRANSCRIPTION; ENHANCER ELEMENT; CDNA CLONES; EXPRESSION; PHOSPHORYLATION; SEQUENCE; PRODUCT AB To gain insight into the cellular regulation of bovine leukemia virus (BLV) trans activation, a lambda-gt11 cDNA library was constructed with mRNA isolated from a BLV-induced tumor and the recombinant proteins were screened with an oligonucleotide corresponding to the tax activation-responsive element (TAR). Two clones (called TAR-binding protein) were isolated from 750,000 lambda-gt11 plaques. The binding specificity was confirmed by Southwestern (DNA-protein) and gel retardation assays. Nucleotide sequence analysis revealed that TAR-binding protein is very similar to the CREB2 protein. It contains a leucine zipper structure required for dimerization, a basic amino acid domain, and multiple potential phosphorylation sites. A vector expressing CREB2 was transfected into D17 osteosarcoma cells. In the absence of the tax transactivator, the CREB2 protein and the cyclic AMP-dependent protein kinase A activate the BLV long terminal repeat at a basal expression level: trans activation reached 10% of the values obtained in the presence of tax alone. These data demonstrate that CREB2 is a cellular factor able to induce BLV long terminal repeat expression in the absence of tax protein and could thus be involved in the early stages of viral infection. In addition, we observed that in vitro tax-induced trans activation can be activated or inhibited by CREB2 depending on the presence or absence of protein kinase A. These data suggest that the cyclic AMP pathway plays a role in the regulation of viral expression in BLV-infected animals. C1 UNIV BRUSSELS,B-1640 RHODE ST GENESE,BELGIUM. NCI,FREDERICK,MD 21701. RP WILLEMS, L (reprint author), FAC AGRON GEMBLOUX,B-5030 GEMBLOUX,BELGIUM. NR 28 TC 45 Z9 46 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1992 VL 66 IS 2 BP 766 EP 772 PG 7 WC Virology SC Virology GA GY965 UT WOS:A1992GY96500018 PM 1309910 ER PT J AU BESS, JW POWELL, PJ ISSAQ, HJ SCHUMACK, LJ GRIMES, MK HENDERSON, LE ARTHUR, LO AF BESS, JW POWELL, PJ ISSAQ, HJ SCHUMACK, LJ GRIMES, MK HENDERSON, LE ARTHUR, LO TI TIGHTLY BOUND ZINC IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1, HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I, AND OTHER RETROVIRUSES SO JOURNAL OF VIROLOGY LA English DT Article ID ROUS-SARCOMA VIRUS; ACID BINDING-PROTEIN; NUCLEOCAPSID PROTEIN; HIV-1 PROTEASE; GENOMIC RNA; MOLECULAR CHARACTERIZATION; STRUCTURAL PROTEINS; METAL-IONS; GAG; SEQUENCE AB Human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type I (HTLV-I) were purified by sucrose density gradient centrifugation in the presence of 1 mM EDTA. Pelleted gradient fractions were analyzed for total protein, total Gag capsid protein, and total zinc. Zinc was found to copurify and concentrate with the virus particles. Through successive cycles of resuspending in buffer containing EDTA and repelleting, the zinc content remained constant at about 1.7 mol of zinc per mol of Gag protein. Proteins from purified virus (HIV-1 and HTLV-I) were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, blotted to polyvinylidene fluoride paper, and probed with (ZnCl2)-Zn-65. Viral nucleocapsid (NC) proteins (HIV-1 p7NC and HTLV-I p15NC) bound Zn-65(2+). Other retroviruses, including simian immunodeficiency virus, equine infectious anemia virus, bovine leukemia virus, Moloney murine leukemia virus, mouse mammary tumor virus, and Mason-Pfizer monkey virus, were found to contain amounts of zinc per milligram of total protein similar to those found in HIV-1 and HTLV-I. Collectively, these data support the hypothesis that retroviral NC proteins function as zinc finger proteins in mature viruses. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,CHEM SYNTH & ANAL LAB,FREDERICK,MD 21702. RP BESS, JW (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,AIDS VACCINE PROGRAM,FREDERICK,MD 21702, USA. RI Bess, Jr., Julian/B-5343-2012 FU NCI NIH HHS [N01-CO-74102] NR 51 TC 131 Z9 133 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1992 VL 66 IS 2 BP 840 EP 847 PG 8 WC Virology SC Virology GA GY965 UT WOS:A1992GY96500026 PM 1731111 ER PT J AU AHN, BY ROSEL, J COLE, NB MOSS, B AF AHN, BY ROSEL, J COLE, NB MOSS, B TI IDENTIFICATION AND EXPRESSION OF RPO19, A VACCINIA VIRUS GENE ENCODING A 19-KILODALTON DNA-DEPENDENT RNA-POLYMERASE SUBUNIT SO JOURNAL OF VIROLOGY LA English DT Article ID TEMPERATURE-SENSITIVE MUTANTS; LATE MESSENGER-RNAS; 5' POLY(A) LEADER; PHENOTYPIC CHARACTERIZATION; 147-KILODALTON SUBUNITS; NUCLEOTIDE-SEQUENCE; FUNCTIONAL-ANALYSIS; PROTEIN-KINASE; FINE-STRUCTURE; TRANSCRIPTION AB The vaccinia virus DNA-dependent RNA polymerase subunit gene rpo19 was identified, and its expression was examined at RNA and protein levels. Antibody to the multisubunit RNA polymerase purified from virions reacted with a polypeptide with an apparent M(r) of 21,000 that was synthesized in reticulocyte lysates programmed with (i) mRNA from infected cells that was isolated by hybridization to DNA subclones of the viral genomic HindIII A fragment and (ii) mRNA made in vitro by transcription of the viral open reading frame A6R. Polyclonal antiserum, raised to a recombinant protein product of the A6R open reading frame which could encode an 18,996-Da protein with an acidic N terminus, reacted with M(r)-21,000 and -22,000 polypeptides that cosedimented with purified RNA polymerase. Internal sequencing of the two polypeptides confirmed that both were encoded by A6R, and the gene was named rpo19 to indicate the predicted molecular mass of the polypeptide in kilodaltons. Immunoblotting and metabolic labeling of infected cell proteins indicated that synthesis of the M(r)-21,000 polypeptide started early and continued throughout virus infection, whereas the M(r)-22,000 form appeared late following DNA replication. RNA analyses suggested that the rpo19 mRNA was expressed from a dual early/late promoter and that the protein-coding region of the mRNA was directly preceded by a short 5' poly(A) leader, apparently initiated within the TAAATG motif at the beginning of the open reading frame. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NR 47 TC 33 Z9 37 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1992 VL 66 IS 2 BP 971 EP 982 PG 12 WC Virology SC Virology GA GY965 UT WOS:A1992GY96500041 PM 1731116 ER PT J AU BOYER, PL FERRIS, AL HUGHES, SH AF BOYER, PL FERRIS, AL HUGHES, SH TI CASSETTE MUTAGENESIS OF THE REVERSE-TRANSCRIPTASE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO JOURNAL OF VIROLOGY LA English DT Article ID ESCHERICHIA-COLI; RNASE-H; DNA-POLYMERASE; GEL-ELECTROPHORESIS; MUTATIONAL ANALYSIS; DOMAIN-STRUCTURE; EXPRESSION; MUTANTS; RIBONUCLEASE; ANTIBODY AB We constructed a series of BspMI cassettes that simplify the introduction of specific point mutations in the polymerase domain of human immunodeficiency virus type 1 reverse transcriptase. A series of point mutants were constructed by using these cassette vectors. The RNA-dependent DNA polymerase and RNase H activities of 20 point mutations in the conserved portion of the polymerase domain were assayed. All the mutations analyzed are conservative substitutions of evolutionarily conserved amino acids. The mutations were divided into four classes. The first class has little effect on either polymerase or RNase H activity. The second class affects RNase H but not polymerase activity, while the third class has a normal RNase H activity with diminished polymerase activity. The fourth class affects both activities. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,POB B,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 44 TC 143 Z9 143 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1992 VL 66 IS 2 BP 1031 EP 1039 PG 9 WC Virology SC Virology GA GY965 UT WOS:A1992GY96500048 PM 1370546 ER PT J AU DAYTON, ET KONINGS, DAM POWELL, DM SHAPIRO, BA BUTINI, L MAIZEL, JV DAYTON, AI AF DAYTON, ET KONINGS, DAM POWELL, DM SHAPIRO, BA BUTINI, L MAIZEL, JV DAYTON, AI TI EXTENSIVE SEQUENCE-SPECIFIC INFORMATION THROUGHOUT THE CAR RRE, THE TARGET SEQUENCE OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REV PROTEIN SO JOURNAL OF VIROLOGY LA English DT Article ID VIRAL MESSENGER-RNA; ART GENE-PRODUCT; HTLV-I REX; HIV-1 REV; TRANS-ACTIVATOR; RESPONSIVE ELEMENT; SUBCELLULAR-LOCALIZATION; FUNCTIONAL-ANALYSIS; SECONDARY STRUCTURE; EXPRESSION AB The significance and location of sequence-specific information in the CAR/RRE, the target sequence for the Rev protein of the human immunodeficiency virus type 1 (HIV-1), have been controversial. We present here a comprehensive experimental and computational approach combining mutational analysis, phylogenetic comparison, and thermodynamic structure calculations with a systematic strategy for distinguishing sequence-specific information from secondary structural information. A target sequence analog was designed to have a secondary structure identical to that of the wild type but a sequence that differs from that of the wild type at every position. This analog was inactive. By exchanging fragments between the wild-type sequence and the inactive analog, we were able to detect an unexpectedly extensive distribution of sequence specificity throughout the CAR/RRE. The analysis enabled us to identify a critically important sequence-specific region, region IIb in the Rev-binding domain, strongly supports a proposed base-pairing interaction in this location, and places forceful constraints on mechanisms of Rev action. The generalized approach presented can be applied to other systems. C1 NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM 11C112,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NCI,DIV CANC BIOL & DIAG,MATH BIOL LAB,FREDERICK,MD 21701. GEORGE WASHINGTON UNIV,DEPT GENET,WASHINGTON,DC 20052. NR 74 TC 57 Z9 58 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1992 VL 66 IS 2 BP 1139 EP 1151 PG 13 WC Virology SC Virology GA GY965 UT WOS:A1992GY96500060 PM 1731093 ER PT J AU PENNA, A FOWLER, P BERTOLETTI, A GUILHOT, S MOSS, B MARGOLSKEE, RF CAVALLI, A VALLI, A FIACCADORI, F CHISARI, FV FERRARI, C AF PENNA, A FOWLER, P BERTOLETTI, A GUILHOT, S MOSS, B MARGOLSKEE, RF CAVALLI, A VALLI, A FIACCADORI, F CHISARI, FV FERRARI, C TI HEPATITIS-B VIRUS (HBV)-SPECIFIC CYTOTOXIC T-CELL (CTL) RESPONSE IN HUMANS - CHARACTERIZATION OF HLA CLASS-II-RESTRICTED CTLS THAT RECOGNIZE ENDOGENOUSLY SYNTHESIZED HBV ENVELOPE ANTIGENS SO JOURNAL OF VIROLOGY LA English DT Note ID TOXIC LYMPHOCYTES-T; RECOMBINANT VACCINIA VIRUS; BREFELDIN-A; ENDOPLASMIC-RETICULUM; EXOGENOUS ANTIGEN; PROTEIN ANTIGENS; SURFACE-ANTIGEN; INVARIANT CHAIN; SYNTHETIC PEPTIDES; SOLUBLE-PROTEIN AB In this study, we show that CD4+, hepatitis B virus (HBV) envelope-specific T-cell clones produced by stimulation with a particulate antigen preparation are able to recognize and kill not only autologous antigen-presenting cells incubated with exogenous HBV envelope antigens but also autologous HLA class II-positive cells expressing endogenously synthesized HBV envelope antigens following infection with recombinant vaccinia viruses or transfection with recombinant Epstein-Barr virus expression vectors. Experiments with lysosomotropic agents and brefeldin A suggest that the endosomal compartment is likely involved in the processing of endogenously synthesized viral proteins for recognition by CD4+ T cells. Our study indicates that HBV envelope-specific, HLA class II-restricted CD4+ cytotoxic T lymphocytes can potentially participate in the immune clearance of HBV-infected cells and the pathogenesis of hepatocellular injury in hepatitis B. C1 SCRIPPS RES INST, DEPT MOLEC & EXPTL MED, LA JOLLA, CA 92037 USA. NIAID, VIRAL DIS LAB, BETHESDA, MD 20892 USA. ROCHE INST MOLEC BIOL, NUTLEY, NJ 07110 USA. RP PENNA, A (reprint author), UNIV PARMA, CATTEDRA MALATTIE INFETT, I-43100 PARMA, ITALY. RI Chisari, Francis/A-3086-2008; Ferrari, Carlo/D-5663-2017; OI Ferrari, Carlo/0000-0002-7843-4963; Chisari, Francis/0000-0002-4832-1044; Bertoletti, Antonio/0000-0002-2942-0485 FU NCRR NIH HHS [RR 00833]; NIAID NIH HHS [AI 20001, AI 26626] NR 47 TC 47 Z9 48 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1992 VL 66 IS 2 BP 1193 EP 1198 PG 6 WC Virology SC Virology GA GY965 UT WOS:A1992GY96500067 PM 1731098 ER PT J AU OWENS, RA CARTER, BJ AF OWENS, RA CARTER, BJ TI INVITRO RESOLUTION OF ADENOASSOCIATED VIRUS-DNA HAIRPIN TERMINI BY WILD-TYPE REP PROTEIN IS INHIBITED BY A DOMINANT-NEGATIVE MUTANT OF REP SO JOURNAL OF VIROLOGY LA English DT Note ID HUMAN-CELLS; REPLICATION; AAV; PARVOVIRUS; GENE; IDENTIFICATION; ANTIBODIES; REPEATS; ORIGIN; GENOME AB An adeno-associated virus (AAV) genome with a Lys-to-His (K340H) mutation in the consensus nucleotide triphosphate binding site of the rep gene has a dominant-negative DNA replication phenotype in vivo. We expressed both wild-type (Rep78) and mutant (Rep78NTP) proteins in two helper-free expression systems consisting of either recombinant baculoviruses in insect cells or the human immunodeficiency virus type 1 long terminal repeat promoter in human 293 cell transient transfections. We analyzed nuclear extracts from both expression systems for the ability to complement uninfected HeLa cell cytoplasmic extracts in an in vitro terminal resolution assay in which a covalently closed AAV terminal hairpin structure is converted to an extended linear duplex. Although both Rep78 and Rep78NTP bound to AAV terminal hairpin DNA in vitro, Rep78 but not Rep78NTP complemented the terminal resolution assay. Furthermore, Rep78NTP was trans dominant for AAV terminal resolution in vitro. We propose that the dominant-negative replication phenotype of AAV genomes carrying the K340H mutation is mediated by mutant Rep proteins binding to the terminal repeat hairpin. C1 NIDDKD,MOLEC & CELLULAR BIOL LAB,BLDG 8,ROOM 304,BETHESDA,MD 20892. NR 26 TC 28 Z9 28 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1992 VL 66 IS 2 BP 1236 EP 1240 PG 5 WC Virology SC Virology GA GY965 UT WOS:A1992GY96500077 PM 1309900 ER PT J AU SUGAMATA, M MIYAZAWA, M MORI, S SPANGRUDE, GJ EWALT, LC LODMELL, DL AF SUGAMATA, M MIYAZAWA, M MORI, S SPANGRUDE, GJ EWALT, LC LODMELL, DL TI PARALYSIS OF STREET RABIES VIRUS-INFECTED MICE IS DEPENDENT ON LYMPHOCYTES-T SO JOURNAL OF VIROLOGY LA English DT Note ID CENTRAL NERVOUS-SYSTEM; CYTO-TOXIC LYMPHOCYTES; IMMUNE-RESPONSE; IA ANTIGENS; MONOCLONAL-ANTIBODY; MEASLES-VIRUS; VIRAL-ANTIGEN; BRAIN-CELLS; RAT-BRAIN; INTERFERON AB Street rabies virus (SRV)-infected T-lymphocyte-deficient (nude) mice, in contrast to euthymic mice, did not develop hindlimb paralysis prior to death. To document the role of T lymphocytes in rabies virus-associated paralysis, 10(8) spleen cells from normal immunocompetent euthymic mice were transferred to nude mice and the recipient mice were challenged with SRV. One hundred percent of the reconstituted mice developed paralysis and died. Depletion of T cells from the donor spleen suspension prior to transfer abrogated the development of paralysis but did not prevent the deaths of the recipient animals. Mice receiving 10(8) rabies virus-immune spleen cells did not become paralyzed and did not die. Nude mice inoculated with either rabies virus-immune or normal mouse serum prior to and following SRV inoculation did not develop paralysis. Immune serum protected the mice, whereas animals inoculated with normal serum died. Central nervous system inflammatory responses in nude mice immunologically reconstituted with normal spleen cells were characterized by diffuse cellular infiltrates in the parenchyma and extensive perivascular cuffing. Perivascular infiltrates included CD8+ and CD4+ T lymphocytes and Mac-1+ macrophage-microglial cells. Inflammatory cells in the parenchyma were limited to CD8+ lymphocytes and Mac-1+ cells. These observations indicate that paralysis of SRV-infected mice is dependent on T lymphocytes. Whether injury leading to paralysis is mediated by T lymphocytes or by an influence of T lymphocytes on macrophage-microglial cells or other cells remains to be determined. C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. NR 49 TC 33 Z9 34 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1992 VL 66 IS 2 BP 1252 EP 1260 PG 9 WC Virology SC Virology GA GY965 UT WOS:A1992GY96500080 PM 1731103 ER PT J AU CONNORS, M KULKARNI, AB COLLINS, PL FIRESTONE, CY HOLMES, KL MORSE, HC MURPHY, BR AF CONNORS, M KULKARNI, AB COLLINS, PL FIRESTONE, CY HOLMES, KL MORSE, HC MURPHY, BR TI RESISTANCE TO RESPIRATORY SYNCYTIAL VIRUS (RSV) CHALLENGE INDUCED BY INFECTION WITH A VACCINIA VIRUS RECOMBINANT EXPRESSING THE RSV M2 PROTEIN (VAC-M2) IS MEDIATED BY CD8+ T-CELLS, WHILE THAT INDUCED BY VAC-F OR VAC-G RECOMBINANTS IS MEDIATED BY ANTIBODIES SO JOURNAL OF VIROLOGY LA English DT Note ID TOXIC LYMPHOCYTES-T; CHORIOMENINGITIS VIRUS; INTERFERON-GAMMA; IMMUNE INTERFERON; FUSION PROTEIN; GLYCOPROTEIN G; HOST IMMUNITY; COTTON RATS; MICE; INFLUENZA AB It was previously demonstrated that the vaccinia virus recombinants expressing the respiratory syncytial virus (RSV) F, G, or M2 (also designated as 22K) protein (Vac-F, Vac-G, or Vac-M2, respectively) induced almost complete resistance to RSV challenge in BALB/c mice. In the present study, we sought to identify the humoral and/or cellular mediators of this resistance. Mice were immunized by infection with a single recombinant vaccinia virus and were subsequently given a monoclonal antibody directed against CD4+ or CD8+ T cells or gamma interferon (IFN-gamma) to cause depletion of effector T cells or IFN-gamma, respectively, at the time of RSV challenge (10 days after immunization). Mice immunized with Vac-F or Vac-G were completely or almost completely resistant to RSV challenge after depletion of both CD4+ and CD8+ T cells prior to challenge, indicating that these cells were not required at the time of virus challenge for expression of resistance to RSV infection induced by the recombinants. In contrast, the high level of protection of mice immunized with Vac-M2 was completely abrogated by depletion of CD8+ T cells, whereas depletion of CD4+ T cells or IFN-gamma resulted in intermediate levels of resistance. These results demonstrate that antibodies are sufficient to mediate the resistance to RSV induced by the F and G proteins, whereas the resistance induced by the M2 protein is mediated primarily by CD8+ T cells, with CD4+ T cells and IFN-gamma also contributing to resistance. C1 NIAID,IMMUNOPATHOL LAB,BETHESDA,MD 20892. RP CONNORS, M (reprint author), NIAID,INFECT DIS LAB,RESP VIRUSES SECT,BLDG 7,ROOM 106,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 34 TC 70 Z9 70 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1992 VL 66 IS 2 BP 1277 EP 1281 PG 5 WC Virology SC Virology GA GY965 UT WOS:A1992GY96500084 PM 1731105 ER PT J AU BAYNE, KAL HURST, JK DEXTER, SL AF BAYNE, KAL HURST, JK DEXTER, SL TI EVALUATION OF THE PREFERENCE TO AND BEHAVIORAL-EFFECTS OF AN ENRICHED ENVIRONMENT ON MALE RHESUS-MONKEYS SO LABORATORY ANIMAL SCIENCE LA English DT Article ID PRIMATES AB Two environments were provided to laboratory rhesus monkeys to determine if the animals spent more time (for the purposes of this study, defined as the cage side preference) in an enriched cage side than an unenriched cage side. The side (right or left) of a double-wide cage in which the animal spent the most time (as determined by Chi square analysis) was initially determined during baseline observations. The "nonpreferred" side was then enriched during the experimental phase of the study. The enrichment consisted of a perch, a Tug-A-Toy(R) suspended inside the cage, a Kong(R) toy suspended on the outside of the cage, and a grooming board mounted on the outside of the cage. No statistically significant changes in use of the enrichments were detected over time. Fifty percent of the animals switched cage side preference to the enriched side during the study. All subjects showed reduced behavioral pathology during exposure to the enriched environment with a return of behavioral pathology when the enrichments were removed. C1 NIMH,NEUROPHYSIOL LAB,BETHESDA,MD 20892. RP BAYNE, KAL (reprint author), NIH,OFF ANIM CARE & USE,ENVIRONM ENRICHMENT LAB,BETHESDA,MD 20892, USA. NR 17 TC 26 Z9 26 U1 1 U2 11 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD FEB PY 1992 VL 42 IS 1 BP 38 EP 45 PG 8 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA HL965 UT WOS:A1992HL96500006 PM 1316507 ER PT J AU ALBRO, PW CORBETT, JT SCHROEDER, JL AF ALBRO, PW CORBETT, JT SCHROEDER, JL TI CHAMBER AND GAVAGE TECHNIQUE FOR METABOLIC STUDIES OF EARTHWORMS SO LABORATORY ANIMAL SCIENCE LA English DT Article AB Earthworms make very suitable laboratory animals for metabolic studies in vivo using radiolabeled test chemicals. We describe the construction and operation of a metabolic chamber to enable the collection of labeled CO2, volatile organics, material excreted into the bedding, and labeled material remaining in the worms. A gavage technique has been developed that permits the administration of water-soluble and lipid-soluble test chemicals in spite of the extremely low level of triglyceride lipase activity in the earthworm gut. This technique is less likely to puncture the worm tissue than previous methods. Radiolabeled DDT and diethylhexyl adipate were used to provide examples of the use of these techniques and the metabolic chamber. Results were qualitatively similar to those that have been noted in vertebrates. RP ALBRO, PW (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 11 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD FEB PY 1992 VL 42 IS 1 BP 63 EP 66 PG 4 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA HL965 UT WOS:A1992HL96500011 PM 1316512 ER PT J AU NOGUERA, R TRICHE, TJ NAVARRO, S TSOKOS, M LLOMBARTBOSCH, A AF NOGUERA, R TRICHE, TJ NAVARRO, S TSOKOS, M LLOMBARTBOSCH, A TI DYNAMIC-MODEL OF DIFFERENTIATION IN EWINGS-SARCOMA CELLS - COMPARATIVE-ANALYSIS OF MORPHOLOGICAL, IMMUNOCYTOCHEMICAL, AND ONCOGENE EXPRESSION PARAMETERS SO LABORATORY INVESTIGATION LA English DT Article DE EWINGS SARCOMA; CELL CULTURE; NEURAL DIFFERENTIATION; DIBUTYRYL CYCLIC AMP; RETINOIC ACID; PHORBOL 12-MYRISTATE 13-ACETATE ID HUMAN NEURO-BLASTOMA; NERVE GROWTH-FACTOR; HEALTH-ORGANIZATION CLASSIFICATION; PERIPHERAL NEUROECTODERMAL TUMORS; ACID-INDUCED DIFFERENTIATION; FREE SUPPLEMENTED MEDIUM; CHILDHOOD BRAIN-TUMORS; ESTABLISHED CULTURES; ELECTRON-MICROSCOPY; MYC ONCOGENE AB We report the establishment of a model of neural differentiation in four well-characterized Ewing's sarcoma cell lines. This process was induced by serum-depleted medium (1% fetal bovine serum) and agents such as dibutyryl cyclic AMP and retinoic acid. The morphologic changes were characterized predominantly by the presence of neurite-like elongated processes showing varicosities and branching along their course with numerous internal filaments and electron-dense granules. Immunocytochemically, differentiation was accompanied by a considerable increase in reactivity for neural markers of several types: neuroblastic, neuroepithelial, neuroendocrine, Schwannian and even glial. In contrast, the tumor promoter, phorbol 12-myristate 13-acetate inhibited differentiation. Several morphologic changes were observed in phorbol 12-myristate 13-acetate-treated cells: the cells became smaller and rounder, were poorly adherent to substrate, by electron microscopy lacked cytoplasmic organelles, electron-dense granules or neural processes, and showed decreased expression of neural markers. Northern blot analysis was performed to establish whether there was any relationship between neural differentiation and degree of N-myc, c-myc and dbl oncogene expression. There was no N-myc oncogene expression in the mRNA of Ewing's sarcoma cells, even after neural induced differentiation. The degree of c-myc and dbl oncogene expression appeared heterogeneous, and varied with the culture condition. Based on these results, it may be inferred that Ewing's sarcoma cells in vitro display a variable neural phenotype, there being a variety of biologic responses to diverse culture media and various differentiation agents, but with no consistent effect on N-myc, c-myc and dbl oncogene expression. C1 UNIV VALENCIA, SCH MED, DEPT PATHOL, AVDA BLASCO IBANEZ 17, E-46010 VALENCIA, SPAIN. CHILDRENS HOSP, DEPT PATHOL & LAB MED, LOS ANGELES, CA 90027 USA. NCI, PATHOL LAB, BETHESDA, MD 20892 USA. NR 61 TC 28 Z9 31 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD FEB PY 1992 VL 66 IS 2 BP 143 EP 151 PG 9 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA HE042 UT WOS:A1992HE04200003 PM 1310513 ER PT J AU PODGORNIK, R PARSEGIAN, VA AF PODGORNIK, R PARSEGIAN, VA TI THERMAL MECHANICAL FLUCTUATIONS OF FLUID MEMBRANES IN CONFINED GEOMETRIES - THE CASE OF SOFT CONFINEMENT SO LANGMUIR LA English DT Article ID PHOSPHOLIPID-BILAYERS; LAMELLAR PHASES; FORCES; TRANSITIONS; HYDRATION; REPULSION AB By definition, membrane or macromolecular assembly is an event of molecular confinement against the configurational entropy of a disordered state. Bilayer membranes under progressive confinement experience a continual damping of undulatory fluctuations, first interpreted as a steric force (Helfrich. Z. Naturforsch. 1978). This paper uses a new, diffusion-equation formalism based on the Feynman-type variational principle to describe how direct interbilayer forces-of hydration, electrostatic double layers, and van der Waals attraction-confine membrane fluctuations. We recover theoretical results to examine measured forces in multilamellar arrays showing that "soft" collisions, through long-range forces, create a mutual enhancement of both the direct forces and the undulatory steric interactions. Thus, there is yet another way to resolve the old, but false, dilemma to choose between steric and direct forces driving membrane assembly. One may develop a systematic connection between bilayer charge, hydration, and flexibility and the action of configurational entropic forces. The results make clear that one should measure forces between membranes or macromolecules in a way that allows them to express their native mechanical freedom. C1 NIDDK,LBM,MOLEC FORCES & ASSEMBLY SECT,BETHESDA,MD 20892. NIH,PHYS SCI LAB,DCRT,BETHESDA,MD 20892. RI Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 18 TC 102 Z9 102 U1 1 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0743-7463 J9 LANGMUIR JI Langmuir PD FEB PY 1992 VL 8 IS 2 BP 557 EP 562 DI 10.1021/la00038a041 PG 6 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA HG566 UT WOS:A1992HG56600041 ER PT J AU LEE, HK AF LEE, HK TI CE ION ANALYSIS SO LC GC-MAGAZINE OF SEPARATION SCIENCE LA English DT Letter C1 NIH,BETHESDA,MD 20892. NATL UNIV SINGAPORE,DEPT CHEM,SINGAPORE 0511,SINGAPORE. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 SN 0888-9090 J9 LC GC-MAG SEP SCI JI LC GC-Mag. Sep. Sci. PD FEB PY 1992 VL 10 IS 2 BP 74 EP 74 PG 1 WC Chemistry, Analytical SC Chemistry GA MP746 UT WOS:A1992MP74600002 ER PT J AU ALBRO, PW SCHROEDER, JL CORBETT, JT AF ALBRO, PW SCHROEDER, JL CORBETT, JT TI LIPIDS OF THE EARTHWORM LUMBRICUS-TERRESTRIS SO LIPIDS LA English DT Article AB The lipid composition of the earthworm Lumbricus terrestris has been reexamined under conditions intended to avoid enzymatic and chemical alterations during storage, extraction, and fractionation procedures. The simple lipids included aliphatic hydrocarbons, steryl esters, glycerides, and at least nine different sterols, all thought to be derived from the diet. Free fatty acids, previously considered to be major components of worm lipids, comprised only 0.3% of the total lipid weight. Phospholipids included (in order of relative abundance) phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol, as well as sphingomyelin. Glycolipids included cerebrosides and sulfatides containing both glucose and galactose, and gangliosides containing glucosamine and sialic acid. The fatty acid compositions of these lipid classes appeared to be a mixture of what are considered typical plant, bacterial, and animal acids. Several fatty acids found in the worms, including cis-vaccenic and eicosapentaenoic acids, were essentially absent from the dietary components, and it is concluded that these acids were synthesized in the worms. The earthworm derives much of its lipid adventitiously, but exerts at least some control over its tissue lipid composition. RP ALBRO, PW (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 45 TC 30 Z9 31 U1 2 U2 10 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 SN 0024-4201 J9 LIPIDS JI Lipids PD FEB PY 1992 VL 27 IS 2 BP 136 EP 143 DI 10.1007/BF02535813 PG 8 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA HD824 UT WOS:A1992HD82400009 PM 1579058 ER PT J AU GIBSON, HL TUCKER, JE KASLOW, DC KRETTLI, AU COLLINS, WE KIEFER, MC BATHURST, IC BARR, PJ AF GIBSON, HL TUCKER, JE KASLOW, DC KRETTLI, AU COLLINS, WE KIEFER, MC BATHURST, IC BARR, PJ TI STRUCTURE AND EXPRESSION OF THE GENE FOR PV200, A MAJOR BLOOD-STAGE SURFACE-ANTIGEN OF PLASMODIUM-VIVAX SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE PLASMODIUM-VIVAX; BLOOD-STAGE ANTIGEN; PV200; MALARIA VACCINE ID CIRCUMSPOROZOITE PROTEIN; SACCHAROMYCES-CEREVISIAE; MONOCLONAL-ANTIBODY; SEQUENCE-ANALYSIS; AOTUS MONKEYS; FALCIPARUM; MALARIA; PRECURSOR; CLONING; YOELII AB Molecular cloning and structure analysis of the gene encoding the Pv200 protein of the Sal-1 strain of Plasmodium vivax revealed an overall identity of 34-37% when the deduced amino acid sequence was compared with the sequences of various major merozoite surface antigens of Plasmodium falciparum, Plasmodium yoelii and Plasmodium chabaudi. When the Sal-1 Pv200 sequence was compared with the corresponding sequence from the Belem strain of P. vivax, it was found that the two merozoite surface antigens were relatively well conserved with an overall amino acid sequence identity of 81%. A region of 23 repeated glutamine residues, found in the sequence of the Belem isolate was not found, however, in the Sal-1 sequence. Amino- and carboxy-terminal domains of the Pv200 protein were expressed in the yeast Saccharomyces cerevisiae. Each recombinant protein was shown to react with antibodies in sera from splenectomized Bolivian Saimiri monkeys that had been infected previously with P. vivax, and in human sera from individuals with a history of exposure to vivax malaria. The availability of recombinant DNA-derived Pv200 proteins will now allow a full assessment of their utility in the diagnosis and immunoprophylaxis of the benign tertian malaria associated with P. vivax infection. C1 CHIRON CORP,4560 HORTON ST,EMERYVILLE,CA 94608. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. CTR DIS CONTROL,CTR INFECT DIS,DIV PARASIT DIS,ATLANTA,GA 30333. NR 30 TC 83 Z9 88 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD FEB PY 1992 VL 50 IS 2 BP 325 EP 334 DI 10.1016/0166-6851(92)90230-H PG 10 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA HC297 UT WOS:A1992HC29700016 PM 1371329 ER PT J AU RYSECK, RP BULL, P TAKAMIYA, M BOURS, V SIEBENLIST, U DOBRZANSKI, P BRAVO, R AF RYSECK, RP BULL, P TAKAMIYA, M BOURS, V SIEBENLIST, U DOBRZANSKI, P BRAVO, R TI RELB, A NEW REL FAMILY TRANSCRIPTION ACTIVATOR THAT CAN INTERACT WITH P50-NF-KAPPA-B SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NF-KAPPA-B; DIVERGENT GAL1-GAL10 PROMOTER; DNA-BINDING SUBUNIT; C-REL; V-REL; PROTO-ONCOGENE; RETICULOENDOTHELIOSIS VIRUS; SACCHAROMYCES-CEREVISIAE; NUCLEOTIDE-SEQUENCE; REGULATORY ELEMENTS AB We have identified a serum-inducible gene, relB, which encodes a protein of 558 amino acids containing a region with high similarity to c-Rel and other members of the Rel family. Transcriptional activation analysis of GAL4-RelB fusion proteins in yeast cells reveals that RelB contains in its C-terminal 180 amino acids a transcriptional activation domain. The N-terminal part including the region of similarity with the Rel family shows no detectable transcriptional activity. RelB does not bind with high affinity to NF-kappa-B sites, but heterodimers between RelB and p50-NF-kappa-B do bind to different NF-kappa-B-binding sites with a similar affinity to that shown by p50-NF-kappa-B homodimers. However, RelB/p50-NF-kappa-B heterodimers, in contrast to p50-NF-kappa-B homodimers, transactivate transcription of a promoter containing a kappa-B-binding site. C1 BRISTOL MYERS SQUIBB,PHARMACEUT RES INST,DEPT MOLEC BIOL,POB 4000,PRINCETON,NJ 08543. CATHOLIC UNIV CHILE,DEPT BIOL CELULAR & MOLEC,SANTIAGO,CHILE. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 63 TC 339 Z9 344 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1992 VL 12 IS 2 BP 674 EP 684 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA HB066 UT WOS:A1992HB06600023 PM 1732739 ER PT J AU BOURS, V BURD, PR BROWN, K VILLALOBOS, J PARK, S RYSECK, RP BRAVO, R KELLY, K SIEBENLIST, U AF BOURS, V BURD, PR BROWN, K VILLALOBOS, J PARK, S RYSECK, RP BRAVO, R KELLY, K SIEBENLIST, U TI A NOVEL MITOGEN-INDUCIBLE GENE-PRODUCT RELATED TO P50/P105-NF-KAPPA-B PARTICIPATES IN TRANSACTIVATION THROUGH A KAPPA-B SITE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN-BINDING SITES; C-REL; V-REL; RETICULOENDOTHELIOSIS VIRUS; TRANSCRIPTION FACTOR; NUCLEOTIDE-SEQUENCE; NUCLEAR FACTOR; 65-KD SUBUNIT; T-CELLS; EXPRESSION AB A Rel-related, mitogen-inducible, kappa-B-binding protein has been cloned as an immediate-early activation gene of human peripheral blood T cells. The cDNA has an open reading frame of 900 amino acids capable of encoding a 97-kDa protein. This protein is most similar to the 105-kDa precursor polypeptide of p50-NF-kappa-B. Like the 105-kDa precursor, it contains an amino-terminal Rel-related domain of about 300 amino acids and a carboxy-terminal domain containing six full cell cycle or ankyrin repeats. In vitro-translated proteins, truncated downstream of the Rel domain and excluding the repeats, bind kappa-B sites. We refer to the kappa-B-binding, truncated protein as p50B by analogy with p50-NF-kappa-B and to the full-length protein as p97. p50B is able to form heteromeric kappa-B-binding complexes with RelB, as well as with p65 and p50, the two subunits of NF-kappa-B. Transient-transfection experiments in embryonal carcinoma cells demonstrate a functional cooperation between p50B and RelB or p65 in transactivation of a reporter plasmid dependent on a kappa-B site. The data imply the existence of a complex family of NF-kappa-B-like transcription factors. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. BRISTOL MYERS SQUIBB,PHARMACEUT RES INST,DEPT MOLEC BIOL,PRINCETON,NJ 08543. UNIV SYDNEY,SCH BIOL SCI,SYDNEY,NSW 2006,AUSTRALIA. NR 50 TC 286 Z9 287 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1992 VL 12 IS 2 BP 685 EP 695 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA HB066 UT WOS:A1992HB06600024 PM 1531086 ER PT J AU RAYCHAUDHURI, G HAYNES, SR BEYER, AL AF RAYCHAUDHURI, G HAYNES, SR BEYER, AL TI HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN COMPLEXES AND PROTEINS IN DROSOPHILA-MELANOGASTER SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RNA-BINDING PROTEINS; HELIX-DESTABILIZING PROTEIN; HNRNP CORE PROTEINS; PRE-MESSENGER RNA; PACKAGING PROTEINS; CALF THYMUS; PARTICLES; DOMAIN; TRANSCRIPTION; CELLS AB Pre-mRNAs cotranscriptionally associate with a small group of proteins to form heterogeneous nuclear ribonucleoprotein (hnRNP) complexes. We have previously identified two genes in Drosophila melanogaster, Hrb98DE and Hrb87F (i.e., genes at 98DE and 87F encoding putative hnRNA binding proteins), which encode five protein species homologous to the mammalian A-B hnRNP proteins. The studies presented herein show that antibodies against the RNP domains of Hrb98DE reacted with 10 to 15 distinct spots of 38 to 40 kDa in the basic region of two-dimensional gels. These nuclear proteins bound single-stranded nucleic acids and were extracted from Drosophila tissue culture cells as 40 to 80S hnRNP complexes in association with 300 to 800 nucleotide fragments of RNA. The peak of poly(A)+ RNA sequences was coincident with the peak of HRB proteins in sucrose gradients, strongly suggesting that the HRB complexes identified are Drosophila hnRNP complexes. The repertoire of HRB proteins did not change significantly during embryogenesis and was similar to that observed in Drosophila tissue culture cells. Analyses with peptide-specific antisera demonstrated that the major proteins in the hnRNP complex were encoded by the two genes previously identified. Although the Drosophila HRB proteins are only approximately 60% identical throughout the RNP domains to the mammalian A-B hnRNP proteins, features of the basic pre-mRNA packaging mechanism appear to be highly conserved between D. melanogaster and mammals. C1 UNIV VIRGINIA,SCH MED,DEPT MICROBIOL,CHARLOTTESVILLE,VA 22908. NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. FU NIGMS NIH HHS [5T32GM08136, GM39271] NR 58 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1992 VL 12 IS 2 BP 847 EP 855 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA HB066 UT WOS:A1992HB06600041 PM 1732749 ER PT J AU MENNITI, FS BIRD, GS GLENNON, MC OBIE, JF ROSSIER, MF PUTNEY, JW AF MENNITI, FS BIRD, GS GLENNON, MC OBIE, JF ROSSIER, MF PUTNEY, JW TI INOSITOL POLYPHOSPHATES AND CALCIUM SIGNALING SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Review ID PAROTID ACINAR-CELLS; PLASMA-MEMBRANE VESICLES; CYTOPLASMIC FREE CALCIUM; HUMAN-ENDOTHELIAL CELLS; INTRACELLULAR CALCIUM; ENDOPLASMIC-RETICULUM; TUMOR PROMOTER; 1,4,5-TRISPHOSPHATE RECEPTOR; NONMUSCLE CELLS; CA-2+ RELEASE RP MENNITI, FS (reprint author), NIEHS,CELLULAR & MOLEC PHARMACOL LAB,CALCIUM REGULAT SECT,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Menniti, Frank/0000-0003-2612-9534 NR 93 TC 34 Z9 34 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell Neurosci. PD FEB PY 1992 VL 3 IS 1 BP 1 EP 10 DI 10.1016/1044-7431(92)90001-I PG 10 WC Neurosciences SC Neurosciences & Neurology GA HF224 UT WOS:A1992HF22400001 PM 19912838 ER PT J AU LEE, WH CLEMENS, JA BONDY, CA AF LEE, WH CLEMENS, JA BONDY, CA TI INSULIN-LIKE GROWTH-FACTORS IN THE RESPONSE TO CEREBRAL-ISCHEMIA SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID CENTRAL NERVOUS-SYSTEM; RAT BINDING-PROTEIN; FACTOR-II; GENE-EXPRESSION; CHOROID-PLEXUS; IGF-II; BRAIN; MACROPHAGES; RECEPTOR; MANNOSE-6-PHOSPHATE C1 ELI LILLY & CO,LILLY RES LAB,INDIANAPOLIS,IN 46202. NIGMS,BETHESDA,MD 20892. RP LEE, WH (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892, USA. NR 28 TC 97 Z9 97 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell Neurosci. PD FEB PY 1992 VL 3 IS 1 BP 36 EP 43 DI 10.1016/1044-7431(92)90006-N PG 8 WC Neurosciences SC Neurosciences & Neurology GA HF224 UT WOS:A1992HF22400006 PM 19912843 ER PT J AU HENDRIX, MJC SEFTOR, EA GROGAN, TM SEFTOR, REB HERSH, EM BOYSE, EA LIOTTA, LA STETLERSTEVENSON, W RAY, CG AF HENDRIX, MJC SEFTOR, EA GROGAN, TM SEFTOR, REB HERSH, EM BOYSE, EA LIOTTA, LA STETLERSTEVENSON, W RAY, CG TI EXPRESSION OF TYPE-IV COLLAGENASE CORRELATES WITH THE INVASION OF HUMAN LYMPHOBLASTOID CELL-LINES AND PATHOGENESIS IN SCID MICE SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE COLLAGENASE-IV; EPSTEIN-BARR VIRUS; LYMPHOMA; INVASION; SCID MOUSE; LYMPHOBLASTOID CELLS ID EPSTEIN-BARR-VIRUS; BASEMENT-MEMBRANE; IMMUNODEFICIENCY; PROCOLLAGEN; DEGRADATION; LYMPHOMA; BURKITTS; LATENCY C1 UNIV ARIZONA,DEPT PATHOL,TUCSON,AZ 85724. UNIV ARIZONA,DEPT PEDIAT,TUCSON,AZ 85724. UNIV ARIZONA,CHILDRENS RES CTR,DEPT MICROBIOL & IMMUNOL,TUCSON,AZ 85724. UNIV ARIZONA,COLL MED,ARIZONA CANC CTR,HEMATOL & ONCOL SECT,TUCSON,AZ 85724. NCI,PATHOL LAB,BETHESDA,MD 20892. RP HENDRIX, MJC (reprint author), UNIV ARIZONA,DEPT ANAT,TUCSON,AZ 85724, USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 FU NCI NIH HHS [CA-170-94] NR 32 TC 22 Z9 24 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD FEB PY 1992 VL 6 IS 1 BP 59 EP 65 DI 10.1016/0890-8508(92)90072-6 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA HF327 UT WOS:A1992HF32700009 PM 1312223 ER PT J AU FUNASAKA, Y BOULTON, T COBB, M YARDEN, Y FAN, BL LYMAN, SD WILLIAMS, DE ANDERSON, DM ZAKUT, R MISHIMA, Y HALABAN, R AF FUNASAKA, Y BOULTON, T COBB, M YARDEN, Y FAN, BL LYMAN, SD WILLIAMS, DE ANDERSON, DM ZAKUT, R MISHIMA, Y HALABAN, R TI C-KIT-KINASE INDUCES A CASCADE OF PROTEIN TYROSINE PHOSPHORYLATION IN NORMAL HUMAN MELANOCYTES IN RESPONSE TO MAST-CELL GROWTH-FACTOR AND STIMULATES MITOGEN-ACTIVATED PROTEIN-KINASE BUT IS DOWN-REGULATED IN MELANOMAS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID HUMAN-MALIGNANT MELANOMA; W-MUTANT MICE; RECEPTOR KINASE; SI-LOCUS; LIGAND; MOUSE; EXPRESSION; ONCOGENE; MUTATIONS; CLONING AB The proto-oncogene c-Kit, a transmembrane receptor tyrosine kinase, is, an important regulator of cell growth whose constitutively active oncogenic counterpart, v-kit, induces sarcomas in cats. Mutations in murine c-kit that reduce the receptor tyrosine kinase activity cause deficiencies in the migration and proliferation of melanoblasts, hematopoietic stem cells, and primordial germ cells. We therefore investigated whether c-Kit regulates normal human melanocyte proliferation and plays a role in melanomas. We show that normal human melanocytes respond to mast cell growth factor (MGF), the Kit-ligand that stimulates phosphorylation of tyrosyl residues in c-Kit and induces sequential phosphorylation of tyrosyl residues in several other proteins. One of the phosphorylated intermediates in the signal transduction pathway was identified as an early response kinase (mitogen-activated protein [MAP] kinase). Dephosphorylation of a prominent 180-kDa protein suggests that MGF also activates a phosphotyrosine phosphatase. In contrast, MGF did not induce proliferation, the cascade of protein phosphorylations, or MAP kinase activation in the majority of cells cultured from primary nodular and metastatic melanomas that grow independently of exogenous factors. In the five out of eight human melanoma lines expressing c-kit mRNAs, c-Kit was not constitutively activated. Therefore, although c-Kit-kinase is a potent growth regulator of normal human melanocytes, its activity is not positively associated with malignant transformation. C1 UNIV TEXAS,SW MED CTR,DEPT PHARMACOL,DALLAS,TX 75235. WEIZMANN INST SCI,DEPT CHEM IMMUNOL,IL-76100 REHOVOT,ISRAEL. IMMUNEX RES & DEV CORP,SEATTLE,WA 98103. NCI,SURG BRANCH,BETHESDA,MD 20892. KOBE UNIV,SCH MED,DEPT DERMATOL,CHUO KU,KOBE 650,JAPAN. RP FUNASAKA, Y (reprint author), YALE UNIV,SCH MED,DEPT DERMATOL,NEW HAVEN,CT 06510, USA. RI YARDEN, YOSEF/K-1467-2012; OI Cobb, Melanie/0000-0003-0833-5473 FU NCI NIH HHS [5-R29-CA44542]; NIAMS NIH HHS [1RO1-AR39848]; NIDDK NIH HHS [DK 34128] NR 87 TC 173 Z9 173 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD FEB PY 1992 VL 3 IS 2 BP 197 EP 209 PG 13 WC Cell Biology SC Cell Biology GA HD215 UT WOS:A1992HD21500007 PM 1372524 ER PT J AU KOSUGI, S BAN, T AKAMIZU, T KOHN, LD AF KOSUGI, S BAN, T AKAMIZU, T KOHN, LD TI IDENTIFICATION OF SEPARATE DETERMINANTS ON THE THYROTROPIN RECEPTOR REACTIVE WITH GRAVES THYROID-STIMULATING ANTIBODIES AND WITH THYROID-STIMULATING BLOCKING ANTIBODIES IN IDIOPATHIC MYXEDEMA - THESE DETERMINANTS HAVE NO HOMOLOGOUS SEQUENCE ON GONADOTROPIN RECEPTORS SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; IMMUNOGLOBULIN-G; CHROMOSOMAL ASSIGNMENT; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; TSH RECEPTOR; DISEASE; AUTOANTIBODIES; CELLS; BINDING AB Deletions, substitutions, or mutations of the rat TSH receptor extracellular domain between residues 20 and 107 (all residue numbers are determined by counting from the methionine start site) have been made by site-directed mutagenesis of receptor cDNA. After transfection in Cos-7 cells, constructs were evaluated for their ability to bind [I-125]TSH or respond to TSH and thyroid-stimulating antibodies (TSAbs) from Graves' patients in assays measuring cAMP levels of the transfected cells. Assay results were compared to results from Cos-7 cells transfected with wild-type receptor constructs or vector alone. We identify threonine-40 as a TSAb-specific site whose mutation to asparagine, but not alanine, reduces TSAb activity 10-fold, but only minimally affects TSH-increased cAMP levels. We show that thyroid-stimulating blocking antibodies (TSBAbs), which block TSH or TSAb activity and are found in hypothyroid patients with idiopathic myxedema, continue to inhibit TSH-stimulated cAMP levels when threonine-40 is mutated to asparagine or alanine, suggesting that TSBAbs interact with different TSH receptor epitopes than the TSAb autoantibodies in Graves' patients. This is confirmed by the demonstration that these TSBAbs interact with high affinity TSH-binding sites previously identified at tyrosine-385 or at residues 295-306 of the extracellular domain of the TSH receptor. This is evidenced by a loss in the ability of TSBAbs to inhibit TSAb activity when these residues are mutated or deleted, respectively. Since the TSAb and TSBAb epitopes are in regions of the extracellular domain of the TSH receptor that have no homology in gonadotropin receptors, these data explain at least in part the organ-specific nature of TSH receptor autoantibodies in autoimmune thyroid disease. Data are additionally provided which indicate that residues 30-37 and 42-45, which flank the TSAb epitope at threonine-40, appear to be ligand interaction sites more important for high affinity TSH binding than for the ability of TSH to increase cAMP levels and that cysteine-41 is critical for TSH receptor conformation and expression on the surface of the cell. Thus, despite unchanged maximal values for TSH-increased cAMP levels, substitution of residues 42-45 or deletion of residues 30-37 results in receptors, which, by comparison to wild-type constructs, exhibit significantly worsened K(d) values for TSH binding than EC50 values for TSH- or TSAb-increased cAMP activity. Mutation of cysteine-41 to serine, however, results in a receptor that expresses no TSH binding or TSH- or TSAb-increased cAMP activity; its deletion, with residue 42, produces a receptor that retains some TSH- or TSAb-increased cAMP activity, but exhibits reduced maximal activity. Mutation of cysteine-31 to serine, in contrast, increases TSH binding as well as both TSH- and TSAb-increased cAMP levels. Residues flanking threonine-40 thus appear to be important for ligand interaction as well as receptor conformation. C1 NIDDKD, BIOCHEM & METAB LAB, CELL REGULAT SECT, BETHESDA, MD 20892 USA. NR 55 TC 83 Z9 83 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 FEB PY 1992 VL 6 IS 2 BP 168 EP 180 DI 10.1210/me.6.2.168 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HH583 UT WOS:A1992HH58300003 PM 1349156 ER PT J AU SHAMAY, A PURSEL, VG WALL, RJ HENNIGHAUSEN, L AF SHAMAY, A PURSEL, VG WALL, RJ HENNIGHAUSEN, L TI INDUCTION OF LACTOGENESIS IN TRANSGENIC VIRGIN PIGS - EVIDENCE FOR GENE AND INTEGRATION SITE-SPECIFIC HORMONAL-REGULATION SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID WHEY ACIDIC PROTEIN; MAMMARY EXPLANTS; FAT SYNTHESIS; BOVINE; PROLACTIN; CASEIN; OVINE; RNA; PROGESTERONE; SECRETION AB Five month-old transgenic female pigs from three lines carrying the mouse whey acidic protein (WAP) gene and nontransgenic female littermates were implanted with slow-release estrogen and progesterone pellets. Histological analysis of biopsies taken at the time of implantation and 4 weeks later revealed that mammary alveolar development had occurred upon hormonal stimulation in vivo. Beta-Casein and beta-lactoglobulin mRNA was found in all induced animals, and WAP mRNA was detected in two of the three transgenic pigs. Differential hormonal regulation between the transgenes in the three lines and also between endogenous milk protein genes was observed in induced mammary tissue cultured in vitro. In the presence of insulin, hydrocortisone, and PRL, beta-casein and WAP mRNA levels increased in all transgenic pigs. In contrast, beta-lactoglobulin mRNA had reached or exceeded lactational levels in response to the in vivo induction, and no further increase was observed in vitro. This suggests that the regulation of the beta-lactoglobulin gene is distinct from that of beta-casein and WAP. Differences were also observed during pregnancy; whereas beta-lactoglobulin gene expression was induced in early pregnancy, a time when PRL levels are low, WAP mRNA levels increased sharply around parturition. Finally, the observation that hormonal regulation of WAP transgenes greatly differed between the three lines suggests that chromatin surrounding the integration site can modify the response of transcription elements. C1 NIDDKD,BIOCHEM & METAB LAB,BLDG 10,ROOM 9N113,BETHESDA,MD 20892. USDA ARS,BELTSVILLE,MD 20725. NR 17 TC 21 Z9 22 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD FEB PY 1992 VL 6 IS 2 BP 191 EP 197 DI 10.1210/me.6.2.191 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HH583 UT WOS:A1992HH58300005 PM 1569963 ER PT J AU MARKS, MS LEVI, BZ SEGARS, JH DRIGGERS, PH HIRSCHFELD, S NAGATA, T APPELLA, E OZATO, K AF MARKS, MS LEVI, BZ SEGARS, JH DRIGGERS, PH HIRSCHFELD, S NAGATA, T APPELLA, E OZATO, K TI H-2RIIBP EXPRESSED FROM A BACULOVIRUS VECTOR BINDS TO MULTIPLE HORMONE RESPONSE ELEMENTS SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID CLASS-I GENE; HUMAN GLUCOCORTICOID RECEPTOR; THYROID-HORMONE; RETINOIC ACID; REGULATORY ELEMENT; ESTROGEN-RECEPTOR; INDUCIBLE ENHANCER; NUCLEAR RECEPTOR; AMINO-ACIDS; BETA-GENE AB H-2RIIBP is a member of the nuclear hormone receptor superfamily that binds to the region II enhancer of major histocompatibility complex class I genes. Based on its homology with Drosophila XR2C/CF1, H-2RIIBP may play a role in development. By using a baculovirus expression system, a large amount of recombinant H-2RIIBP was produced. The recombinant protein accumulated in the nucleus of insect cells. A series of monoclonal antibodies reacting with the recombinant H-2RIIBP was then generated. A DNA-protein immunoprecipitation assay was developed with these antibodies, enabling the DNA-binding specificity of H-2RIIBP to be distinguished from that of an endogenous region II binding factor expressed in uninfected insect cells. We show that H-2RIIBP binds to estrogen response elements with an affinity comparable to that for the region II enhancer. H-2RIIBP also bound to some, but not all, thyroid hormone response elements and retinoic acid response elements, albeit at a lower affinity. Binding to these elements was demonstrated without exogenous addition of a ligand. The H-2RIIBP binding specificity determined by this assay was in agreement with the specificity assessed by Southwestern and gel mobility shift assays. Furthermore, methylation interference assays indicated that H-2RIIBP recognizes the conserved hormone response motif GG(T/A)CA. Taken together, these data demonstrate that H-2RIIBP is capable of binding to hormone response elements of a variety of genes. They suggest that H-2RIIBP may exert a pleiotropic function. C1 NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892. TECHNION ISRAEL INST TECHNOL,DEPT FOOD ENGN & BIOTECHNOL,IL-32000 HAIFA,ISRAEL. NCI,CELL BIOL LAB,BETHESDA,MD 20892. RI Hirschfeld, Steven/E-2987-2016; OI Hirschfeld, Steven/0000-0003-0627-7249; Marks, Michael/0000-0001-7435-7262 NR 60 TC 34 Z9 34 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD FEB PY 1992 VL 6 IS 2 BP 219 EP 230 DI 10.1210/me.6.2.219 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HH583 UT WOS:A1992HH58300008 PM 1569965 ER PT J AU MEIER, CA DICKSTEIN, BM ASHIZAWA, K MCCLASKEY, JH MUCHMORE, P RANSOM, SC MENKE, JB HAO, EH USALA, SJ BERCU, BB CHENG, SY WEINTRAUB, BD AF MEIER, CA DICKSTEIN, BM ASHIZAWA, K MCCLASKEY, JH MUCHMORE, P RANSOM, SC MENKE, JB HAO, EH USALA, SJ BERCU, BB CHENG, SY WEINTRAUB, BD TI VARIABLE TRANSCRIPTIONAL ACTIVITY AND LIGAND-BINDING OF MUTANT BETA-1 3,5,3'-TRIIODOTHYRONINE RECEPTORS FROM 4 FAMILIES WITH GENERALIZED RESISTANCE TO THYROID-HORMONE SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID C-ERBA; 3 FORMS; GENE; DOMAIN; EXPRESSION; ACTIVATION; KINDREDS; MUTATION; TISSUES; MEDIATE AB Mutations in the gene encoding the human beta-1 T3 receptor (hTR-beta-1) have been associated with generalized resistance to thyroid hormone (GRTH). We measured the T3-binding affinity and transcriptional regulatory capacity of the mutant hTR-beta-1 from four unrelated kindreds with GRTH. These mutations are contained in different functional regions of the ligand-binding domain. The T3 affinity of the mutant receptors correlated well with the degree of impairment of their trans-activating function in a transient cotransfection system in HeLa cells; two mutant receptors with undetectable ligand affinity showed no transcriptional activity, whereas the two other mutants characterized by a 2- and 5-fold reduction in T3 affinity required 5- and 15-fold higher T3 concentrations for half-maximal activity in the cotransfection assay, respectively. All of the mutant hTR-beta-1s were able to inhibit the function of transfected normal hTR-beta-1 and endogenous retinoic acid receptor in activating a palindromic positive T3 response element (TRE). In the partially functional mutants this dominant negative effect could be completely reversed by increased T3 concentrations. The dominant negative potency did not depend on the type of TRE used; mutant hTR-beta-1s were able to inhibit normal receptor function to the same degree on a dimer-permissive palindromic TRE as on a nondimer-permissive inverted repeat of two identical half-sites separated by five spacer bases. However, the dominant negative potency was dependent on the absolute amount of receptor expression vector transfected. The expression of normal and mutant hTR-beta-1 was assessed by immunocytochemistry. The hTR-beta-1 protein levels in HeLa cells paralleled the amount of transfected expression vector. Moreover, all the mutant receptors were properly expressed in the nuclei of the transfected cells. These data suggest that different mutations in the ligand-binding domain of the human hTR-beta-1 result in a variable degree of functional impairment, which may partially explain the phenotypic differences between kindreds with GRTH. Our findings suggest that competition for binding to the TRE and possibly the binding of limiting accessory factors may be more important in mediating the dominant negative effect than the formation of normal/mutant T3 receptor dimers. C1 NIDDKD, MOLEC CELLULAR & NUTR ENDOCRINOL BRANCH, BLDG 10, ROOM 8014, BETHESDA, MD 20892 USA. NCI, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. E CAROLINA UNIV, SCH MED, DEPT MED, GREENVILLE, NC 27858 USA. UNIV S FLORIDA, COLL MED, DEPT PEDIAT, TAMPA, FL 33612 USA. ALL CHILDRENS HOSP, ST PETERSBURG, FL 33731 USA. FU NIDDK NIH HHS [DK-42807-01] NR 42 TC 124 Z9 125 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD FEB PY 1992 VL 6 IS 2 BP 248 EP 258 DI 10.1210/me.6.2.248 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HH583 UT WOS:A1992HH58300011 PM 1569968 ER PT J AU TOWNSEND, AJ TU, CPD COWAN, KH AF TOWNSEND, AJ TU, CPD COWAN, KH TI EXPRESSION OF HUMAN MU OR ALPHA CLASS GLUTATHIONE S-TRANSFERASES IN STABLY TRANSFECTED HUMAN MCF-7 BREAST-CANCER CELLS - EFFECT ON CELLULAR-SENSITIVITY TO CYTOTOXIC AGENTS SO MOLECULAR PHARMACOLOGY LA English DT Article ID DRUG-RESISTANCE; MULTIDRUG RESISTANCE; CONFERS RESISTANCE; NITROGEN MUSTARDS; P-GLYCOPROTEIN; GENES; TUMORS; LINES; CHLORAMBUCIL; ADRIAMYCIN AB Increased expression of certain glutathione S-transferase (GST) isoenzymes has frequently been associated with the development of resistance to alkylating agents and other classes of antineoplastic drugs in drug-selected cell lines. The question arises whether this phenomenon is causal or is a stress-induced response associated with drug resistance in these cell lines. We have constructed mammalian expression vectors containing the human GST-mu and GST-alpha-2 (Ha2) cDNAs and stably transfected them into the human breast cancer cell line MCF-7. Whereas the parental and pSV2neo-transfected cell lines display low GST activity, three individual transfected clones were identified in each group that expressed either GST-mu or GST-alpha-2. The range of GST activities was similar to those observed in cells selected for anticancer drug resistance. The GST-mu specific activities were 56, 150, and 340 mIU/mg, compared with 10 mIU/mg of endogenous GST-mu in control lines. Specific activities in GST-alpha-2-transfected clones were 17, 28, and 52 mIU/mg, compared with no detectable alpha class GST in control lines. These clonal lines and the parental and pSV2neo-transfected control lines were tested for sensitivity to antineoplastic agents and other cytotoxic compounds. The clones with the highest activity in each group were 1.7-fold (GST-alpha-2) to 2.1-fold (GST-mu) resistant to the toxic effects of ethacrynic acid, a known substrate for GSTs. However, the GST-transfected cell lines were not resistant to doxorubicin, L-phenylalanine mustard, bis(2-chloroethyl)-1-nitrosourea, cisplatin, chlorambucil, or the GST substrates 1-chloro-2,4-dinitrobenzene or tert-butyl hydroperoxide. Thus, although L-phenylalanine mustard, bis(2-chloroethyl)-1-nitrosourea, chlorambucil, tert-butyl hydroperoxide, and 1-chloro-2,4-dinitrobenzene are known to be metabolized by glutathione-dependent GST-catalyzed reactions, there was no protection against any of these agents in MCF-7 cell lines overexpressing GST-mu or GST-alpha-2. We conclude that, at the levels of GST obtained in this transfection model system, overexpression of GST-mu or GST-alpha-2 is not by itself sufficient to confer resistance to these anticancer agents. These studies do not exclude the possibility that GST may be a marker of drug resistance or that other gene products not expressed in MCF-7 cells might cooperate with GST to confer drug resistance. C1 NCI,MED BRANCH,BLDG 10,ROOM 12N226,BETHESDA,MD 20892. PENN STATE UNIV,DEPT MOLEC & CELL BIOL,UNIV PK,PA 16802. NR 41 TC 69 Z9 71 U1 0 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD FEB PY 1992 VL 41 IS 2 BP 230 EP 236 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HL472 UT WOS:A1992HL47200003 PM 1538704 ER PT J AU TSUTSUMI, K SAAVEDRA, JM AF TSUTSUMI, K SAAVEDRA, JM TI HETEROGENEITY OF ANGIOTENSIN-II AT-2 RECEPTORS IN THE RAT-BRAIN SO MOLECULAR PHARMACOLOGY LA English DT Article ID ATRIAL-NATRIURETIC-PEPTIDE; NUCLEOTIDE-BINDING PROTEIN; ISLET-ACTIVATING PROTEIN; SUBFORNICAL ORGAN; PERTUSSIS TOXIN; PARAVENTRICULAR NUCLEUS; ANTERIOR-PITUITARY; DIVALENT-CATIONS; SITES; AUTORADIOGRAPHY AB Angiotensin II (AT) receptor subtypes (AT1, selectively displaced by DuP 753, and AT2, selectively displaced by PD123177 and CGP42112A) were characterized by quantitative autoradiography after incubation with the AT agonist I-125-Sar1-AT, in specific brain nuclei of young (2-week-old) rats. Binding to AT1 receptors was sensitive (decreased affinity) to incubation in the presence of guanosine 5'-O-(3-thio)triphosphate (GTP-gamma-S). Only the AT1 receptors in the paraventricular nucleus were sensitive to pertussis toxin, indicating the possibility of the existence of AT1 receptor subtypes. The sensitivity of AT2 receptors to GTP-gamma-S was heterogeneous. In the ventral thalamic and medial geniculate nuclei and in the locus coeruleus, binding to AT2 receptors was sensitive to GTP-gamma-S and to pertussis toxin pretreatment. Conversely, in the inferior olive, binding was insensitive to GTP-gamma-S and to pertussis toxin pretreatment. We propose the nomenclature of AT2A receptors for those receptors sensitive to guanine nucleotides and pertussis toxin and that of AT2B receptors for those showing no sensitivity to guanine nucleotides or pertussis toxin treatment. C1 NIMH,CLIN SCI LAB,PHARMACOL SECT,9000 ROCKVILLE PIKE,BLDG 10,ROOM 2D-45,BETHESDA,MD 20892. NR 56 TC 132 Z9 132 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD FEB PY 1992 VL 41 IS 2 BP 290 EP 297 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HL472 UT WOS:A1992HL47200011 PM 1538709 ER PT J AU BRESSLER, JP EDWARDS, NA AF BRESSLER, JP EDWARDS, NA TI GLIAL SHAPE AND CYTOSKELETAL PROTEIN-SYNTHESIS SO NEUROCHEMICAL RESEARCH LA English DT Article DE SHAPE; ASTROCYTE; INTERMEDIARY FILAMENT; GLIOMA ID FIBRILLARY ACIDIC PROTEIN; ASTROCYTES; VIMENTIN; EXPRESSION; ELECTROPHORESIS; FILAMENTS; MIGRATION AB We investigated whether the shape of astroglial derived cells influences the expression of cytoskeletal proteins. In reaggregating cultures GFAP, vimentin and actin synthesis was approximately 52%, 50% and 37% the level found in monolayer cultures, respectively. Monolayer cultures consisted of polygonal shaped cells adhering to plastic, while reaggregating cultures were comprised of round cells growing in a suspension like culture. Additionally, human glioma cells induced to grow as round cells on poly-2-hydroxyethyl methacrylate (polyhema) coated plastic exhibited a level of GFAP synthesis that was approximately 20% the level displayed by polygonal shaped cells grown on uncoated plastic. Glioma cells initially grown on a polyhema surface and replated onto uncoated plastic were capable of reinitiating GFAP synthesis. Thus, aterations in the synthesis of GFAP and other cytoskeletal proteins can occur when astrocytes change their shape. C1 NIH,SURG NEUROL BRANCH,BETHESDA,MD 20892. RP BRESSLER, JP (reprint author), KENNEDY RES INST,DEPT NEUROL,707 N BROADWAY,BALTIMORE,MD 21205, USA. FU NEI NIH HHS [7 RO1 EY 02772-12]; NIEHS NIH HHS [5 RO1 ES02380-12] NR 29 TC 2 Z9 2 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD FEB PY 1992 VL 17 IS 2 BP 173 EP 177 DI 10.1007/BF00966796 PG 5 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA HC451 UT WOS:A1992HC45100008 PM 1538832 ER PT J AU BRADY, LS LYNN, AB WHITFIELD, HJ KIM, H HERKENHAM, M AF BRADY, LS LYNN, AB WHITFIELD, HJ KIM, H HERKENHAM, M TI INTRAHIPPOCAMPAL COLCHICINE ALTERS HYPOTHALAMIC CORTICOTROPIN-RELEASING HORMONE AND HIPPOCAMPAL STEROID-RECEPTOR MESSENGER-RNA IN RAT-BRAIN SO NEUROENDOCRINOLOGY LA English DT Article DE COLCHICINE; CORTICOTROPIN-RELEASING HORMONE MESSENGER RNA; DENTATE GYRUS; GLUCOCORTICOID RECEPTOR MESSENGER RNA; HYPOTHALAMUS INOSITOL 1,4,5-TRISPHOSPHATE KINASE MESSENGER RNA; INSITU HYBRIDIZATION; MINERALOCORTICOID RECEPTOR MESSENGER RNA; PARAVENTRICULAR NUCLEUS ID GRANULE CELLS; MINERALOCORTICOID RECEPTOR; PARAVENTRICULAR NUCLEUS; DENTATE GYRUS; LOCALIZATION; EXPRESSION; NEURONS; IMMUNOREACTIVITY; ORGANIZATION; DESTRUCTION AB The hippocampus appears to be an important modulator of the negative feedback effects of glucocorticoids on the hypothalamic-pituitary-adrenal axis. It is not known if hippocampal subfields CA1-4 or the dentate gyrus differentially alter gene expression of corticotropin-releasing hormone (CRH) in the paraventricular nucleus (PVN) of the hypothalamus. We, therefore, examined the effects of selective destruction of dentate gyrus granule cells, which send excitatory glutaminergic inputs to subfields CA4, CA3 and CA2, on CRH expression in the PVN. To determine the possible involvement of steroid receptors in the regulation of CRH expression, we examined the effects of intrahippocampal colchicine on gene expression of the mineralocorticoid (MR; type I) and glucocorticoid (GR; type II) receptors in hippocampal CA fields and dentate gyrus. Colchicine produced a selective loss of dentate gyrus granule cells without affecting pyramidal cells in CA1-4 as early as 1 day after injection; granule cells were completely destroyed after 3 days. CRH mRNA levels were reduced by 38-48% in the PVN 2-14 days after colchicine. MR mRNA levels were decreased in dorsal and ventral CA fields 1-7 days after colchicine. GR mRNA levels were relatively unchanged, showing a slight decrease only in dorsal CA fields on days 2-7. Unexpectedly, CRH was transiently expressed in dorsal and ventral CA fields 1-3 days after colchicine. In the same time period, mRNA levels of inositol 1,4,5-trisphosphate kinase were decreased, suggesting that increases in neural metabolic activity, indicated by this marker, are not responsible for the transient CRH effect. The results suggest that the dentate gyrus is important for maintenance of steroid hormone receptor mRNA levels in the hippocampus and CRH expression in the hypothalamic PVN, and that CRH gene expression is differentially regulated in the hypothalamus and hippocampus. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RP BRADY, LS (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,FUNCT NEUROANAT SECT,BLDG 36,BETHESDA,MD 20892, USA. OI Herkenham, Miles/0000-0003-2228-4238 NR 40 TC 18 Z9 20 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD FEB PY 1992 VL 55 IS 2 BP 121 EP 133 DI 10.1159/000126107 PG 13 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA HE141 UT WOS:A1992HE14100001 PM 1320216 ER PT J AU BARANIUK, JN LUNDGREN, JD SHELHAMER, JH KALINER, MA AF BARANIUK, JN LUNDGREN, JD SHELHAMER, JH KALINER, MA TI GASTRIN RELEASING PEPTIDE (GRP) BINDING-SITES IN HUMAN BRONCHI SO NEUROPEPTIDES LA English DT Article ID IMMUNOHISTOCHEMICAL LOCALIZATION; RESPIRATORY-TRACT; SENSORY NEURONS; BOMBESIN; LUNG; CAPSAICIN; TETRADECAPEPTIDE; STIMULATION; TACHYKININS; CELLS AB The autoradiographic binding site of gastrin releasing peptide (GRP), the 27 amino acid mammalian form of bombesin, were examined in human bronchial mucosa. I-125-GRP bound specifically to submucosal glands and the epithelium. There was limited binding to vessels and bronchial smooth muscle. These observations suggest that GRP or GRP immunoreactive peptides which are present in nerve fibres and pulmonary neuroendocrine cells, may act upon glandular GRP receptors to induce mucus secretion, but that GRP would probably have little effect on vascular permeability or tracheobronchial smooth muscle tone. C1 NIAID,ALLERGEN DIS SECT,CLIN INVEST LAB,BLDG 10,ROOM 11-C-205,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT CRIT CARE,BETHESDA,MD 20892. OI Lundgren, Jens/0000-0001-8901-7850 NR 25 TC 11 Z9 11 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD FEB PY 1992 VL 21 IS 2 BP 81 EP 84 DI 10.1016/0143-4179(92)90518-2 PG 4 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA HE569 UT WOS:A1992HE56900003 PM 1557184 ER PT J AU UHDE, TW TANCER, ME RUBINOW, DR ROSCOW, DB BOULENGER, JP VITTONE, B GURGUIS, G GERACI, M BLACK, B POST, RM AF UHDE, TW TANCER, ME RUBINOW, DR ROSCOW, DB BOULENGER, JP VITTONE, B GURGUIS, G GERACI, M BLACK, B POST, RM TI EVIDENCE FOR HYPOTHALAMO-GROWTH HORMONE DYSFUNCTION IN PANIC DISORDER - PROFILE OF GROWTH-HORMONE (GH) RESPONSES TO CLONIDINE, YOHIMBINE, CAFFEINE, GLUCOSE, GRF AND TRH IN PANIC DISORDER PATIENTS VERSUS HEALTHY-VOLUNTEERS SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE PANIC DISORDER; ANXIETY; GROWTH HORMONE; GROWTH HORMONE-RELEASING FACTOR; SOMATOSTATIN; SOMATOTROPIN RELEASE-INHIBITING FACTOR; THYROTROPIN-RELEASING HORMONE; CLONIDINE; YOHIMBINE; CAFFEINE; GLUCOSE; HYPOGLYCEMIA; ADENOSINE; ADRENERGIC; SOMATOMEDIN; BLOOD; CEREBROSPINAL FLUID; STATURE ID THYROTROPIN-RELEASING-HORMONE; INSULIN-INDUCED HYPOGLYCEMIA; ADRENERGIC-RECEPTOR SENSITIVITY; CENTRAL NERVOUS-SYSTEM; NORADRENERGIC FUNCTION; BIOCHEMICAL MANIFESTATIONS; POSTPRANDIAL HYPOGLYCEMIA; ENDOGENOUS-DEPRESSION; PROLACTIN SECRETION; BLOOD-PRESSURE AB Given the abrupt and time-limited nature of daytime-awake and nocturnal-sleep panic attacks, several chemical and neuroendocrine challenge tests have been employed to investigate the neurobiology of "spontaneous" panic attacks. Previously we demonstrated that panic disorder patients have blunted growth hormone (GH) responses to clonidine, an alpha-2-adrenergic agonist. However, the mechanism of this blunted response and the role of hypothalamic-GH dysfunction, if any, remains unclear. To further delineate the status Of hypothalamic-GH function in panic disorder, we review the literature and present original data on the GH responses to a number of different chemical and neuroendocrine challenge paradigms. Although stress-mediated increases in GH are thought to be a common correlate of stress in humans, our findings indicate that panic disorder patients have significantly blunted GH responses to clonidine, yohimbine, growth-hormone releasing factor, and caffeine compared to normal control subjects. A similar trend was noted in the delayed rise in GH after glucose challenge. There was no difference in the rate of abnormal GH responses to thyrotropin-releasing hormone in panic disorder compared to normal control subjects. No drug or neuroendocrine challenge, even if associated with marked increases in anxiety, produced a significantly enhanced GH response compared to normal control subjects. These findings provide support for a hyporesponsive hypothalamic-GH system in panic disorder. These observations, combined with preliminary observations from our clinic of short stature in several cases of prepubescent children with anxiety disorders, also underscore the need for assessing early growth patterns in individuals with panic disorder. Strategies for investigating the site(s) of possible neurotransmitter or hypothalamic-GH-somatomedin dysfunction are discussed. C1 NIMH,BIOL PSYCHIAT BRANCH,BEHAV ENDOCRINOL SECT,BETHESDA,MD 20892. RP UHDE, TW (reprint author), NIMH,BIOL PSYCHIAT BRANCH,ANXIETY & AFFECT DISORDERS SECT,BLDG 10,BETHESDA,MD 20892, USA. NR 132 TC 57 Z9 57 U1 3 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD FEB PY 1992 VL 6 IS 2 BP 101 EP 118 PG 18 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA HP331 UT WOS:A1992HP33100005 PM 1610485 ER PT J AU NOGUCHI, K DUBNER, R RUDA, MA AF NOGUCHI, K DUBNER, R RUDA, MA TI PREPROENKEPHALIN MESSENGER-RNA IN SPINAL DORSAL HORN NEURONS IS INDUCED BY PERIPHERAL INFLAMMATION AND IS CO-LOCALIZED WITH FOS AND FOS-RELATED PROTEINS SO NEUROSCIENCE LA English DT Article ID MULTIPLE OPIOID SYSTEMS; IMMEDIATE-EARLY GENES; INSITU HYBRIDIZATION; PROJECTION NEURONS; NEURAL CIRCUITRY; MET-ENKEPHALIN; RAT MODEL; STIMULATION; EXPRESSION; PAIN AB Increased levels of preproenkephalin mRNA in spinal cord neurons induced by peripheral tissue inflammation were examined using in situ hybridization histochemistry. In addition, in situ hybridization histochemistry was combined with immunocytochemistry to determine whether increases in prepoenkephalin mRNA were co-localized in spinal cord neurons with increases in immunoreactivity for Fos and Fos-related proteins coded by the immediate-early proto-oncogene, c-fos, and related genes. Dorsal horn laminae I-II, V-VI and VII showed a greater than 200% increase in preproenkephalin mRNA-labeled neurons on the inflamed side as compared to the contralateral control. Inflammation also induced Fos-like immunoreactivity in cell nuclei, mainly in the superficial laminae I-II and the neck of the dorsal horn (laminae V-VI). Few labeled nuclei were detected on the contralateral side. Inflammation resulted in double-labeling of neurons ipsilateral to the inflamed limb whereas they were almost completely absent on the contralateral side. Double-labeled neurons were most frequently found in laminae V-VI. Double-labeled laminae I-II neurons were concentrated in the medial two-thirds of the dorsal horn, the site that receives innervation from the inflamed limb. There were also many double-labeled neurons in laminae VII. Over 90%, 82% and 69% of all neurons expressing preproenkephalin mRNA co-localized Fos immunoreactivity in laminae V-VI, I-II, and VII, respectively. However, the number of neurons expressing increased Fos immunoreactivity was substantially greater than the subpopulation of double-labeled neurons. Our findings indicated that peripheral inflammation induces an increase in preproenkephalin mRNA levels in spinal cord neurons and that most neurons exhibiting preproenkephalin mRNA labeling also co-localized Fos and Fos-related immunoreactivity. These data are consistent with evidence supporting the role of Fos and Fos-related proteins in the regulation of transcription of the preproenkephalin gene in spinal neurons. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. NR 45 TC 157 Z9 158 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 FEB PY 1992 VL 46 IS 3 BP 561 EP 570 DI 10.1016/0306-4522(92)90144-Q PG 10 WC Neurosciences SC Neurosciences & Neurology GA HA869 UT WOS:A1992HA86900006 PM 1545910 ER PT J AU BONDY, C WERNER, H ROBERTS, CT LEROITH, D AF BONDY, C WERNER, H ROBERTS, CT LEROITH, D TI CELLULAR-PATTERN OF TYPE-I INSULIN-LIKE GROWTH-FACTOR RECEPTOR GENE-EXPRESSION DURING MATURATION OF THE RAT-BRAIN - COMPARISON WITH INSULIN-LIKE GROWTH FACTOR-I AND FACTOR-II SO NEUROSCIENCE LA English DT Article ID CENTRAL NERVOUS-SYSTEM; IGF-II; QUANTITATIVE AUTORADIOGRAPHY; PROGENITOR CELLS; BINDING-SITES; PROTEIN; LOCALIZATION; SURVIVAL; NEURONS; SERUM AB Insulin-like growth factors have a number of potent trophic effects on cultured neural tissue and most if not all of these effects appear to be mediated by the type-I insulin-like growth factor receptor. In order to establish the identity of cell types expressing this receptor in the rat central nervous system during development and maturity, we have used in situ hybridization to map sites of type-I insulin-like growth factor receptor mRNA synthesis in the developing and adult rat brain. In order to identify possible local sources of peptide ligands for this receptor, we have also mapped the sites of insulin-like growth factors I and II mRNA synthesis in parallel brain sections. From early development onward, there is a uniform and stable pattern of type-I insulin-like growth factor receptor gene expression in all neuroepithelial cell lineages, in which regional variations reflect primarily differences in cell density. In addition to this generalized pattern, during late postnatal development, high levels of type-I insulin-like growth factor receptor gene expression are found in specific sets of sensory and cerebellar projection neurons in conjunction with abundant insulin-like growth factor-I gene expression in these same neurons. While insulin-like growth factor-I expression is confined to the principal neurons in each system, receptor mRNA is also found in local interneurons. In the cerebral cortex and hippocampal formation, type-I insulin-like growth factor receptor mRNA and insulin-like growth factor-I are concentrated in different cell populations: receptor mRNA is abundant in pyramidal cells in Ammon's horn, in granule cells in the dentate gyrus, and in pyramidal cells in lamina VI of the cerebral cortex. Insulin-like growth factor-I mRNA is found in isolated medium- to large-sized cells which are rather irregularly distributed throughout the hippocampus and isocortex. In the hypothalamus, receptor mRNA is concentrated in the suprachiasmatic nucleus but is in low abundance elsewhere, including the median eminence, while insulin-like growth factor-I mRNA is not detected in this region at all. Type-I insulin-like growth factor receptor and insulin-like growth factor-II mRNAs are both abundant in choroid plexus, meninges and vascular sheaths from early development to maturity, but insulin-like growth factor-II mRNA is not detected in cells of neuroepithelial origin at any stage of development. This study provides evidence for two fundamentally different patterns of gene expression for the brain type-I insulin-like growth factor receptor. Firstly, there is a relatively stable and uniform level of receptor gene expression shared by all neuroepithelial lineages. This receptor distribution may be the target of circulating insulin-like growth factors, which are secreted into the bloodstream by the liver and into the cerebrospinal fluid by the choroid plexus, and subserve a very basic metabolic or trophic function. Secondly, superimposed upon this apparently constitutive pattern, during the course of postnatal differentiation, specific sets of neurons show high levels of type-I receptor gene expression in conjunction with local insulin-like growth factor-I expression. These findings suggest that there are specific local fields of paracrine and/or autocrine insulin-like growth factor-I action mediated by the type-I receptor in the brain parenchyma. C1 NIDDK,DIABET BRANCH,BETHESDA,MD 20892. RP BONDY, C (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,RM 10N262,BETHESDA,MD 20892, USA. NR 32 TC 283 Z9 285 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD FEB PY 1992 VL 46 IS 4 BP 909 EP 923 DI 10.1016/0306-4522(92)90193-6 PG 15 WC Neurosciences SC Neurosciences & Neurology GA HB526 UT WOS:A1992HB52600010 PM 1311816 ER PT J AU KENNISON, JA TAMKUN, JW AF KENNISON, JA TAMKUN, JW TI TRANSREGULATION OF HOMEOTIC GENES IN DROSOPHILA SO NEW BIOLOGIST LA English DT Review DE DROSOPHILA; ANTENNAPEDIA COMPLEX; BITHORAX COMPLEX; HOMEODOMAIN; TRANSCRIPTIONAL REGULATION ID DOSAGE-DEPENDENT MODIFIERS; YEAST HO GENE; BITHORAX COMPLEX; LARVAL CUTICLE; ZYGOTIC LOCI; TRANSCRIPTIONAL ACTIVATION; ANTENNAPEDIA GENE; BINDING PROTEIN; HOMEOBOX GENES; TRITHORAX GENE C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. RP KENNISON, JA (reprint author), UNIV CALIF SANTA CRUZ,DEPT BIOL,SANTA CRUZ,CA 95064, USA. NR 55 TC 25 Z9 25 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4674 J9 NEW BIOL PD FEB PY 1992 VL 4 IS 2 BP 91 EP 96 PG 6 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA JR310 UT WOS:A1992JR31000002 PM 1348185 ER PT J AU EHRENREICH, H BURD, PR ROTTEM, M HULTNER, L HYLTON, JB GARFIELD, M COLIGAN, JE METCALFE, DD FAUCI, AS AF EHRENREICH, H BURD, PR ROTTEM, M HULTNER, L HYLTON, JB GARFIELD, M COLIGAN, JE METCALFE, DD FAUCI, AS TI ENDOTHELINS BELONG TO THE ASSORTMENT OF MAST-CELL DERIVED AND MAST-CELL BOUND CYTOKINES SO NEW BIOLOGIST LA English DT Article DE ENDOTHELIN; ENDOTHELIN RECEPTORS; MAST CELLS; HISTAMINE; IGE; DEGRANULATION ID SMOOTH-MUSCLE CELLS; VASOACTIVE INTESTINAL CONTRACTOR; VASOCONSTRICTOR PEPTIDE; MESANGIAL CELLS; MESSENGER-RNA; GLIAL-CELLS; C-FOS; RAT; EXPRESSION; RECEPTOR C1 GESELL STRAHLEN & UMWELTFORSCH MBH,INST EXPTL HEMATOL,MUNICH,GERMANY. NIAID,CLIN INVEST LAB,MAST CELL PHYSIOL SECT,BETHESDA,MD 20892. NIAID,BIOL RESOURCES BRANCH,BETHESDA,MD 20892. RP EHRENREICH, H (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 31,ROOM 7A03,BETHESDA,MD 20892, USA. NR 45 TC 89 Z9 90 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4674 J9 NEW BIOL PD FEB PY 1992 VL 4 IS 2 BP 147 EP 156 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA JR310 UT WOS:A1992JR31000009 PM 1313283 ER PT J AU HSU, VW KLAUSNER, RD FINE, JS KRUISBEEK, AM BANIYASH, M AF HSU, VW KLAUSNER, RD FINE, JS KRUISBEEK, AM BANIYASH, M TI CHANGES IN THE METHYLATION PATTERN OF THE TCR ZETA-CHAIN GENE CORRELATE WITH ITS EXPRESSION IN T-CELLS AND DEVELOPING THYMOCYTES SO NEW BIOLOGIST LA English DT Article DE METHYLATION; ZETA-GENE; T-CELL; THYMOCYTES ID NATURAL-KILLER-CELLS; ANTIGEN RECEPTOR; DNA METHYLATION; ETA-CHAIN; COMPLEX; CD3-ZETA; FC; IDENTIFICATION; TRANSCRIPTION; SPECIFICITY C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. NCI,BIOL RESPONSE MODIFIERS PROGRAM,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,HADASSAH MED SCH,LAUTENBERG CTR GEN & TUMOR IMMUNOL,IL-91010 JERUSALEM,ISRAEL. NR 31 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4674 J9 NEW BIOL PD FEB PY 1992 VL 4 IS 2 BP 166 EP 171 PG 6 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA JR310 UT WOS:A1992JR31000011 PM 1372823 ER PT J AU GOLDENBERG, RL HOFFMAN, HJ CLIVER, SP CUTTER, GR NELSON, KG COPPER, RL AF GOLDENBERG, RL HOFFMAN, HJ CLIVER, SP CUTTER, GR NELSON, KG COPPER, RL TI THE INFLUENCE OF PREVIOUS LOW-BIRTH-WEIGHT ON BIRTH-WEIGHT, GESTATIONAL-AGE, AND ANTHROPOMETRIC MEASUREMENTS IN THE CURRENT PREGNANCY SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID INTRAUTERINE GROWTH-RETARDATION; RECURRENCE; PREDICTION; DELIVERY; RISKS AB The effect of a previous low birth weight birth (less than 2750 g) was examined using a series of regression analyses. Effects on birth weight were partitioned into those associated with preterm delivery (128 g) and term delivery (178 g). Among term births, a mean difference of 107 g was associated with a previous birth of less than 2750 g, even after controlling for other risk factors including smoking, drug and alcohol use, maternal race, size, and hypertension. The pattern of measurements seen after a previous birth of less than 2750 g included significantly smaller head, chest, abdomen, arm, and thigh circumferences, but an insignificant impact on skinfold thicknesses and no significant effect on length measurements. C1 UNIV ALABAMA,SCH PUBL HLTH,BIRMINGHAM,AL 35233. CHILDRENS HOSP,DEPT PEDIAT,BIRMINGHAM,AL. NICHHD,PREVENT RES PROGRAM,BETHESDA,MD 20892. RP GOLDENBERG, RL (reprint author), UNIV ALABAMA,DEPT OBSTET & GYNECOL,PERINATAL EPIDEMIOL UNIT,UNIV STN,BIRMINGHAM,AL 35233, USA. FU NICHD NIH HHS [N01-HD-4-2811] NR 19 TC 17 Z9 17 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 1992 VL 79 IS 2 BP 276 EP 280 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA HB189 UT WOS:A1992HB18900023 PM 1731299 ER PT J AU GRAZIANI, G NEBREDA, AR SRIVASTAVA, S SANTOS, E EVA, A AF GRAZIANI, G NEBREDA, AR SRIVASTAVA, S SANTOS, E EVA, A TI INDUCTION OF XENOPUS OOCYTE MEIOTIC MATURATION BY THE DBL ONCOGENE PRODUCT SO ONCOGENE LA English DT Article ID CDC2 PROTEIN-KINASE; H-1 HISTONE KINASE; CELL-CYCLE; PROMOTING FACTOR; M-PHASE; MOLECULAR-CLONING; PHOSPHOLIPASE-C; RAS PROTEINS; GENE-PRODUCT; EXPRESSION AB The dbl oncogene was originally identified by transfection of NIH3T3 cells with DNA from a human diffuse B-cell lymphoma. The dbl oncogene product is a cytoplasmic phosphoprotein distributed between the cytosolic and cytoskeletal matrix-associated membrane fractions. Nucleotide sequence analysis has indicated that the predicted dbl product is very hydrophilic with no detectable similarity to known oncogene products. We have more recently discovered that a region of dbl essential for its transforming activity shows significant sequence similarity to a yeast cell cycle gene, CDC24, which is involved in cell polarity and bud formation in the division cycle of Saccharomyces cerevisiae. This sequence similarity suggests a possible role for dbl in cell division. We report here that the dbl oncogene product is able to induce maturation of Xenopus oocytes. Germinal vesicle breakdown (GVBD) was observed when oocytes were microinjected with the soluble fraction of SF9 insect cells infected with a dbl recombinant baculovirus as well as with the in vitro-transcribed dbl mRNA. Moreover, extracts of oocytes microinjected with dbl mRNA showed activation of H1 histone kinase activity. These findings define a new biologic activity of the dbl product and provide the opportunity to analyse dbl interactions with other components of signaling pathways involved in oocyte maturation. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT PATHOL & SURG,BETHESDA,MD 20814. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. RI Graziani, Grazia/G-5747-2012; Eva, Alessandra/J-8268-2016; OI Eva, Alessandra/0000-0003-2949-078X; GRAZIANI, GRAZIA/0000-0002-0221-768X FU NCI NIH HHS [CA-46455] NR 45 TC 6 Z9 6 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB PY 1992 VL 7 IS 2 BP 229 EP 235 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA HG982 UT WOS:A1992HG98200004 PM 1312693 ER PT J AU DAMICO, D CARBONE, D MITSUDOMI, T NAU, M FEDORKO, J RUSSELL, E JOHNSON, B BUCHHAGEN, D BODNER, S PHELPS, R GAZDAR, A MINNA, JD AF DAMICO, D CARBONE, D MITSUDOMI, T NAU, M FEDORKO, J RUSSELL, E JOHNSON, B BUCHHAGEN, D BODNER, S PHELPS, R GAZDAR, A MINNA, JD TI HIGH-FREQUENCY OF SOMATICALLY ACQUIRED P53 MUTATIONS IN SMALL-CELL LUNG-CANCER CELL-LINES AND TUMORS SO ONCOGENE LA English DT Article ID POLYMERASE CHAIN-REACTION; POINT MUTATIONS; T-ANTIGEN; SHORT ARM; WILD-TYPE; GENE; CHROMOSOME-17; EXPRESSION; IDENTIFICATION; LOCALIZATION AB We analysed the p53 open reading frame (ORF) in 16 small-cell lung cancer (SCLC) cell lines by direct sequencing of cDNA/PCR products and in 20 SCLC tumors by chemical cleavage and single-strand conformation polymorphism analyses of genomic DNA/PCR products. Abnormalities of p53 were found in 16/16 cell lines (100%) and in 16/20 tumors (80%). In the SCLC cell lines, mutations (59% missense, 18% nonsense and 23% splicing) changing the coding sequence were dispersed between amino acids 68 and 342. In the tumor samples, while the mutations occurred predominantly in exons 5-8, other mutations were located outside these regions. G to T transversions were common, occurring in 32% of the cases. We found no p53 mutations in the corresponding normal tissue from 19 patients whose tumors had p53 lesions, indicating that the mutations were all somatically acquired. In analysing the clinical data of the patients we found no correlation between tumor response to therapy or survival and the location or type of mutations. We conclude from these data that: (1) p53 mutations are found in SCLC with high frequency; (2) p53 mutations in a significant fraction of cases generate cDNAs with nonsense or splicing mutations; and (3) to date, these mutations have all been somatically acquired events. C1 NATL NAVAL MED CTR, NCI, NAVY MED ONCOL BRANCH, BETHESDA, MD 20814 USA. UNIFORMED SERV UNIV HLTH SCI, BETHESDA, MD 20814 USA. RP DAMICO, D (reprint author), UNIV TEXAS, SW MED CTR DALLAS, SIMMONS CANC CTR, 5323 HARRY HINES BLVD, DALLAS, TX 75235 USA. OI Mitsudomi, Tetsuya/0000-0001-9860-8505 NR 58 TC 200 Z9 201 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB PY 1992 VL 7 IS 2 BP 339 EP 346 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA HG982 UT WOS:A1992HG98200020 PM 1312696 ER PT J AU DAVIS, JL SOLOMON, D NUSSENBLATT, RB PALESTINE, AG CHAN, CC AF DAVIS, JL SOLOMON, D NUSSENBLATT, RB PALESTINE, AG CHAN, CC TI IMMUNOCYTOCHEMICAL STAINING OF VITREOUS CELLS - INDICATIONS, TECHNIQUES, AND RESULTS SO OPHTHALMOLOGY LA English DT Article ID PARS-PLANA VITRECTOMY; INFECTIOUS ENDOPHTHALMITIS; INTRAOCULAR LYMPHOMA; UVEITIS; DIAGNOSIS; LYMPHOCYTES; MANAGEMENT; RETINITIS; NEOPLASIA; SARCOMA AB Diagnostic vitrectomy is often performed because of suspected infection or malignancy. Giemsa, Gram, and Papanicolaou stains are used routinely to identify the components in the vitreous. Immunocytochemical staining of cellular components of vitreous specimens has the potential to significantly increase the amount of useful information that can be gained from histopathologic study. Vitreous specimens from 14 patients undergoing diagnostic or therapeutic vitrectomy for infection, suspected primary intraocular lymphoma, or uveitis were examined by immunocytochemical staining using monoclonal antibodies specific for leukocyte subclass antigens and immunoglobulin. The three classes of disorders showed characteristic patterns of staining, which were useful in confirming microbiologic and clinical diagnoses. Infections showed more pronounced neutrophils and macrophages, primary intraocular lymphomas demonstrated light chain restriction of the malignant B lymphocytes, and uveitis was characterized by the predominance of T lymphocytes. The routine use of immunocytochemical staining is recommended to characterize cellular infiltrates and increase the diagnostic yield from vitrectomy specimens. C1 NEI,IMMUNOL LAB,BLDG 10,ROOM 10N206,BETHESDA,MD 20892. NCI,PATHOL LAB,CYTOPATHOL SECT,BETHESDA,MD 20892. NR 37 TC 68 Z9 72 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD FEB PY 1992 VL 99 IS 2 BP 250 EP 256 PG 7 WC Ophthalmology SC Ophthalmology GA HC225 UT WOS:A1992HC22500022 PM 1553217 ER PT J AU FOX, PC AF FOX, PC TI SALIVARY-GLAND INVOLVEMENT IN HIV-1 INFECTION SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; AIDS-RELATED COMPLEX; ORAL FINDINGS; HIGH-RISK; HTLV-III; VIRUS; PEOPLE AB After infection with human immunodeficiency virus (HIV)-1, virus can be recovered from both whole saliva (the total fluid contents of the mouth) and individual major salivary gland secretions. The concentration of virus is low, and recovery is infrequent. Antibodies (primarily of the IgA class) to HIV-1 are found in saliva. Despite the presence of virus, the oral cavity does not appear to be a route of transmission for HIV-1. This may relate to protective properties of saliva. It has been reported that whole saliva and mixed submandibular/sublingual secretions inhibit the infectivity of the virus in vitro. HIV infection also induces alterations in salivary gland function. Both salivary output and composition may be affected. RP FOX, PC (reprint author), NIDR,BLDG 10,ROOM 1N-113,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 19 TC 13 Z9 13 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD FEB PY 1992 VL 73 IS 2 BP 168 EP 170 DI 10.1016/0030-4220(92)90190-2 PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA HD243 UT WOS:A1992HD24300013 PM 1549311 ER PT J AU KOVACIK, V PANNELL, LK KOVAC, P AF KOVACIK, V PANNELL, LK KOVAC, P TI THE B/E LINKED SCAN OF THE FAST-ATOM-BOMBARDMENT SPECTRA - A POWERFUL TOOL FOR THE SEQUENCE-ANALYSIS OF OLIGOSACCHARIDES SO ORGANIC MASS SPECTROMETRY LA English DT Letter ID METHYL BETA-GLYCOSIDES; MASS-SPECTROMETRY; (1->6)-BETA-D-GALACTOOLIGOSACCHARIDES; O-(3-DEOXY-3-FLUORO-BETA-D-GALACTOPYRANOSYL)-(1->6)-O-BETA-D-GALACTOPYRA NOSYL-(. RP KOVACIK, V (reprint author), NIDDK,BETHESDA,MD 20892, USA. NR 8 TC 9 Z9 9 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0030-493X J9 ORG MASS SPECTROM JI Org. Mass Spectrom. PD FEB PY 1992 VL 27 IS 2 BP 159 EP 160 DI 10.1002/oms.1210270218 PG 2 WC Chemistry, Organic; Spectroscopy SC Chemistry; Spectroscopy GA HF606 UT WOS:A1992HF60600017 ER PT J AU LINDBERG, RLP JUVONEN, R NEGISHI, M AF LINDBERG, RLP JUVONEN, R NEGISHI, M TI MOLECULAR CHARACTERIZATION OF THE MURINE COH LOCUS - AN AMINO-ACID DIFFERENCE AT POSITION 117 CONFERS HIGH AND LOW COUMARIN 7-HYDROXYLASE ACTIVITY IN P450COH SO PHARMACOGENETICS LA English DT Article AB Coumarin 7-hydroxylase (P450coh) and steroid 15alpha-hydroxylase (P450(15alpha)) are encoded by members within the mouse 2A subfamily. Since P450coh activity is regulated by the Coh locus, we characterized P450coh cDNAs in strains having high coumarin 7-hydroxylase activity (Coh(H) homozygote) including 129/J and DBA/2J, and compared them with P450coh cDNAs in low activity strains (Coh(L) homozygote) C57BL/6J, C3H/HeJ and AKR/J. The nucleotide sequences of these two cDNAs differ by a single base, which results in an amino acid difference at position 117 (Val in P450coh(H) and Ala in P450coh(L)). The Coh(H) phenotype exhibits approximately 10-fold greater V(max) and four-fold lower Km values than those in the Coh(L). Male 129AKF1/J expresses approximately equal amounts of P450coh(H) and P450coh(L) mRNAs, associated with two Coh alleles. The levels of P450coh and P450(15alpha) mRNAs in the F1 offspring suggested that a trans-acting factor(s) appeared to regulate the expressions of the P450 genes. A recent duplication in the ancestral mouse established the line of descent to P450(15alpha) from the ancestral P450coh gene. During evolution, amino acid substitutions have selectively occurred at positions which alter the enzyme's substrate specificity and increase in the specific activity. Consistent with an important role of natural selection in the evolution of these genes is the relatively high nonsynonomous substitution rates on the P450(15alpha) and the P450coh branches. As a result of these evolution events, the gene family consists of members which exhibit an extremely high degree of structural similarity, but very divergent hydroxylase activities and modes of regulation. C1 NIEHS,REPRODUCT & DEV TOXICOL LAB,PHARMACOGENET SECT,POB 12233,RES TRIANGLE PK,NC 27709. NR 0 TC 25 Z9 25 U1 0 U2 1 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD FEB PY 1992 VL 2 IS 1 BP 32 EP 37 DI 10.1097/00008571-199202000-00006 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA LG851 UT WOS:A1992LG85100005 PM 1302041 ER PT J AU TERRY, P AF TERRY, P TI DIFFERENTIAL-EFFECTS OF INJECTION REGIMEN ON BEHAVIORAL-RESPONSES TO COCAINE SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE CUMULATIVE DOSING; COCAINE; LOCOMOTOR ACTIVITY; SENSITIZATION; SEIZURE; MOUSE ID SENSITIZATION; RATS; AMPHETAMINE; STIMULATION; STRESS AB Locomotor behavior was measured in mice receiving IP cocaine at 5, 10, 20, or 40 mg/kg. Mice in the cumulatively dosed treatment were injected first with saline and then with 5, 5, 10, and 20 mg/kg at 10-min intervals. In the single-dose treatment, mice received a single dose of cocaine at a time corresponding to the equivalent cumulative dose, with saline injections at other times. The single-injection treatment was similar, but saline injections were omitted. Locomotor activity was measured across each 10-min interval. Mice were retested 6 weeks later and 1 day after that. Dose-response curves were similar for all three treatments on the first test, but diverged markedly on subsequent tests. Significant locomotor sensitization occurred at the higher doses on the second test, particularly in the treatments receiving single cocaine injections. On the third test, convulsions occurred at 40 mg/kg, but only in the singly dosed treatments. The results demonstrate that injection parameters can modify both the behavioral and toxic effects of cocaine. RP TERRY, P (reprint author), NATL INST DRUG ABUSE,ADDICT RES CTR,PSYCHOBIOL LAB,POB 5180,BALTIMORE,MD 21224, USA. NR 21 TC 21 Z9 21 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD FEB PY 1992 VL 41 IS 2 BP 365 EP 369 DI 10.1016/0091-3057(92)90112-S PG 5 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA HM764 UT WOS:A1992HM76400017 PM 1574527 ER PT J AU WITKIN, JM GENOVESE, RF WITKIN, KM CHIANG, PK AF WITKIN, JM GENOVESE, RF WITKIN, KM CHIANG, PK TI BEHAVIORAL-EFFECTS OF SOME DIPHENYL-SUBSTITUTED ANTIMUSCARINICS - COMPARISON WITH COCAINE AND ATROPINE SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE ATROPINE; BENACTYZINE; AZAPROPHEN; COCAINE; LOCOMOTOR ACTIVITY; FIXED-INTERVAL SCHEDULES; DISCRIMINATIVE STIMULUS EFFECTS; BEHAVIORAL EFFECTS; RATS ID SCHEDULE-CONTROLLED BEHAVIOR; SQUIRREL-MONKEY; DOPAMINE UPTAKE; AZAPROPHEN; PHYSOSTIGMINE; PHARMACOLOGY; ANTAGONISTS; SCOPOLAMINE; INHIBITORS; AGENTS AB To more fully characterize the behavioral excitatory effects observed with certain diphenyl-substituted antimuscarinics, various behavioral effects of benactyzine, a prototype excitatory antimuscarinic, was evaluated in rats. These effects were compared to those of cocaine, atropine, and azaprophen, a muscarinic antagonist that contains both the diphenyl substituents of benactyzine and a ring isomeric with the tropane ring of atropine. Under a fixed-interval 5-min schedule of food presentation, cocaine and benactyzine increased response rates. Atropine and azaprophen only decreased responding. The muscarinic agonist oxotremorine attenuated the rate-increasing effects but did not alter the disruptions in the temporal patterning produced by benactyzine or shift the dose-effect function to the right. In rats discriminating 10 mg/kg cocaine from saline, benactyzine partially substituted for cocaine, producing a maximum of 50% cocaine-appropriate responses. Benactyzine fully substituted for scopolamine in rats discriminating 0.056 mg/kg scopolamine from saline. All antimuscarinics increased locomotor activity when activity levels were low in control animals, but the increases were less than those produced by cocaine. Cocaine increased both locomotor activity and fixed-interval responding at comparable doses, whereas 10-fold higher doses of benactyzine were required to increase locomotor activity. These results support the following conclusions: 1) In addition to its classical antimuscarinic behavioral profile, benactyzine has behavioral excitatory actions similar in some respects to those of cocaine; 2) the behavioral excitatory effects of benactyzine do not appear to be due solely to antagonism of muscarinic receptors; and 3) the alkyl-ester may be an important structural feature of diphenyl-substituted antimuscarinics for the induction of behavioral stimulation. C1 WEINBERG CONSULTING GRP INC,WASHINGTON,DC 20036. WALTER REED ARMY MED CTR,DEPT MED NEUROSCI,WASHINGTON,DC 20307. WALTER REED ARMY MED CTR,DEPT APPL BIOCHEM,WASHINGTON,DC 20307. RP WITKIN, JM (reprint author), NIDA,ADDICT RES CTR,PSYCHOBIOL LAB,DRUG DEV GRP,POB 5180,BALTIMORE,MD 21224, USA. NR 27 TC 5 Z9 5 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD FEB PY 1992 VL 41 IS 2 BP 377 EP 384 DI 10.1016/0091-3057(92)90114-U PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA HM764 UT WOS:A1992HM76400019 PM 1574528 ER PT J AU LONG, JM DAVIS, BJ GAROFALO, P SPANGLER, EL INGRAM, DK AF LONG, JM DAVIS, BJ GAROFALO, P SPANGLER, EL INGRAM, DK TI COMPLEX MAZE PERFORMANCE IN YOUNG AND AGED RATS - RESPONSE TO GLUCOSE TREATMENT AND RELATIONSHIP TO BLOOD INSULIN AND GLUCOSE SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE LEARNING; MEMORY; CHOLINERGIC SYSTEM; BRAIN METABOLISM; GLUCOSE TOLERANCE; AGING ID 14-UNIT T-MAZE; MEMORY DYSFUNCTION; ENHANCEMENT; METABOLISM; HUMANS; ACQUISITION; SCOPOLAMINE; HYPOTHESIS; MODULATION; IMPAIRMENT AB In aged rats and humans, impaired glucose regulation has been correlated with poor memory performance, and glucose treatment can result in improved performance. We tested this glucose hypothesis with rats in a 14-unit T-maze that has provided robust evidence of age-related performance decline. Aged (24-25 month) and young (6-7 month) male F-344 rats were pretrained for one-way active avoidance before receiving complex maze training (4 daily trials over 5 days) with the contingency of moving through each of 5 segments to avoid footshock. Ten min before daily training, aged rats received either saline or glucose in doses of 10, 100, or 500 mg/kg IP, while young rats received saline. Significant (ps < 0.05) age-related increases in errors, runtime, and shock duration were observed. Glucose treatment had no significant effect on the number of maze errors committed; however, performance variables such as runtime and shock duration appeared to be reduced in rats receiving glucose. About 4-6 weeks later, a sample of these rats was fasted overnight, injected IP with glucose (150 mg/kg), and bled at various postinjection intervals to obtain estimates of blood glucose and insulin levels. Significant correlations (ps < 0.05) were observed between maze errors and baseline glucose levels, r(21) = -.62, and peak glucose response, r(19) = .49. However, within the aged group, significant correlations (ps < 0.01) with maze errors emerged only for baseline glucose, r(13) = -.69, and peak insulin response, r(13) = -.65. Thus, regulation of insulin, but not glucose, appeared related to learning abilities among aged rats. In a second experiment, young (6 month) F-344 rats were given 500 mg/kg glucose IP immediately after the third trial in the 14-unit T-maze. This glucose treatment had no significant effects on maze performance when the rats were retested 24-h later. C1 NIA,GERONTOL RES CTR,NATHAN W SHOCK LABS,MOLEC PHYSIOL & GENET SECT,BALTIMORE,MD 21224. UNIV ROCHESTER,SCH MED,DEPT NEUROL,ROCHESTER,NY 14627. UNIV ROCHESTER,SCH MED,DEPT NEUROBIOL,ROCHESTER,NY 14627. NR 47 TC 30 Z9 30 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD FEB PY 1992 VL 51 IS 2 BP 411 EP 418 DI 10.1016/0031-9384(92)90159-Y PG 8 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA HA082 UT WOS:A1992HA08200027 PM 1313593 ER PT J AU NEWHOUSE, JR TOOLEY, PW SMITH, OP FISHEL, RA AF NEWHOUSE, JR TOOLEY, PW SMITH, OP FISHEL, RA TI CHARACTERIZATION OF DOUBLE-STRANDED-RNA IN ISOLATES OF PHYTOPHTHORA-INFESTANS FROM MEXICO, THE NETHERLANDS, AND PERU SO PHYTOPATHOLOGY LA English DT Article DE EPIDEMIOLOGY; LATE BLIGHT; MOLECULAR MARKER ID NUCLEAR-DNA CONTENT; A2 MATING TYPE; ENDOTHIA-PARASITICA; NUCLEOTIDE-SEQUENCE; STRAINS; DSRNA AB Seventy-nine isolates of Phytophthora infestans, from Mexico, the Netherlands, Peru, Israel, and the United States, were screened for the incidence of double-stranded (ds) RNA. The dsRNA was most abundant in Mexican isolates (83.3%), followed by isolates from the Netherlands (20%) and Peru (2.9%). P. infestans isolates from Israel and the United States were dsRNA-free. Double-stranded RNA was found in both A1 and A2 mating-type Mexican isolates, while only A2 mating-type isolates from the Netherlands contained dsRNA. Dutch and Peruvian isolates contained dsRNA segments that were identical in size with dsRNA segments recovered from Mexican isolates. In addition to the dsRNA segments and patterns previously reported in Mexican isolates, three new segments and six new patterns were discovered. The dsRNAs ranged in size from 1.35 to 11.10 kbp, and transmission electron microscopy of the dsRNA revealed linear molecules. Northern blot hybridization analysis showed that sequence homology exists between comigrating dsRNA segments of Mexican, Dutch, and Peruvian isolates, and that at least four nonhomologous groups of dsRNA occur in P. infestans. C1 FREDERICK CANC RES FACIL,CHROMOSOME BIOL LAB,FREDERICK,MD 21701. RP NEWHOUSE, JR (reprint author), USDA ARS,FOREIGN DIS WEED SCI RES UNIT,FT DETRICK BLDG 1301,FREDERICK,MD 21702, USA. NR 31 TC 20 Z9 21 U1 0 U2 0 PU AMER PHYTOPATHOLOGICAL SOC PI ST PAUL PA 3340 PILOT KNOB ROAD, ST PAUL, MN 55121 SN 0031-949X J9 PHYTOPATHOLOGY JI Phytopathology PD FEB PY 1992 VL 82 IS 2 BP 164 EP 169 DI 10.1094/Phyto-82-164 PG 6 WC Plant Sciences SC Plant Sciences GA HC430 UT WOS:A1992HC43000008 ER PT J AU KORGE, BP GAN, SQ MCBRIDE, OW MISCHKE, D STEINERT, PM AF KORGE, BP GAN, SQ MCBRIDE, OW MISCHKE, D STEINERT, PM TI EXTENSIVE SIZE POLYMORPHISM OF THE HUMAN KERATIN-10 CHAIN RESIDES IN THE C-TERMINAL V2 SUBDOMAIN DUE TO VARIABLE NUMBERS AND SIZES OF GLYCINE LOOPS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INTERMEDIATE FILAMENTS; CYTOKERATIN SUBFAMILY; COMPLETE SEQUENCE; COILED-COIL; II KERATINS; EXPRESSION; GENE; MOUSE; IDENTIFICATION; POLYPEPTIDES AB Existing data suggest that the human keratin. 10 intermediate filament protein is polymorphic in amino acid sequence and in size. To precisely define the nature of the polymorphism, we have used PCR amplification and sequence analyses on DNA from several individuals including rive with documented size variations of the keratin 10 protein. We found no variation in the N-terminal or rod domain sequences. However, we observed many variations in the V2 subdomain near the C terminus in glycine-rich sequences with a variation of as much as 114 base pairs (38 amino acids), but all individuals had either one or two variants. Our results show that (i) the keratin 10 system is far more polymorphic than previously realized, (ii) the polymorphism is restricted to insertions and deletions of the glycine-rich quasipeptide repeats that form the glycine-loop motif in the C-terminal domain, (iii) the polymorphism can be accounted for by simple allelic variations that segregate by normal Mendelian mechanisms, and (iv) the differently sized PCR products most likely represent different alleles of a single-copy gene per haploid genome. C1 NIAMSD,SKIN BIOL LAB,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. FREE UNIV BERLIN,UNIV MED CTR RUDOLF VIRCHOW,INST EXPTL ONCOL & TRANSPLANTAT MED,W-1000 BERLIN 33,GERMANY. NR 35 TC 76 Z9 77 U1 0 U2 2 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 1 PY 1992 VL 89 IS 3 BP 910 EP 914 DI 10.1073/pnas.89.3.910 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HC385 UT WOS:A1992HC38500029 PM 1371013 ER PT J AU NAGATA, T SEGARS, JH LEVI, BZ OZATO, K AF NAGATA, T SEGARS, JH LEVI, BZ OZATO, K TI RETINOIC ACID-DEPENDENT TRANSACTIVATION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I PROMOTERS BY THE NUCLEAR HORMONE RECEPTOR H-2RIIBP IN UNDIFFERENTIATED EMBRYONAL CARCINOMA-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID THYROID-HORMONE; GLUCOCORTICOID RECEPTOR; RESPONSE ELEMENT; REGULATORY ELEMENT; ESTROGEN-RECEPTOR; NEGATIVE REGULATION; GENE-EXPRESSION; STEM-CELLS; BINDING; ACTIVATION AB H-2RIIBP is a member of the nuclear hormone receptor superfamily that binds to the region II enhancer of major histocompatibility complex (MHC) class I genes. The binding occurs through the GG(T/A)CA motif present also in many, other genes. The role of H-2RIIBP in developmental regulation of MHC class I genes has been studied in undifferentiated N-Tera2 embryonal carcinoma cells by transient cotransfection of an expressible H-2RIIBP plasmid and a chloramphenicol acetyltransferase reporter gene linked to the MHC class I promoter. Transfection of the expression plasmid led to production of H-2RIIBP transcripts and enhanced MHC class I promoter activity in cells that were treated with retinoic acid but not vet differentiated. Retinoic acid concentrations required for transactivation overlapped with those capable of inducing morphological differentiation and expression of endogenous MHC class I genes in these cells. This enhancement was mediated by region II, as a heterologous thymidine kinase promoter driven by region II also served as a target for H-2RIIBP transactivation. Deletion of the bulk of the DNA-binding domain or the ligand-binding domain of H-2RIIBP, but not of the N-terminal domain, abolished transactivation, indicating that the former two domains are critical for the enhancement. Moreover, H-2RIIBP transactivation exhibited a strict cell-type restriction. As observed in other cell lines, N-Tera2 cells that had undergone differentiation failed to elicit transactivation, suggesting that H-2RIIBP acts in concert with a cofactor expressed in undifferentiated N-Tera2 cells that requires retinoic acid for its function. These results suggest that H-2RIIBP can function as a developmentally specific transcription factor for MHC class I genes. C1 NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892. NR 46 TC 67 Z9 67 U1 0 U2 0 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 1 PY 1992 VL 89 IS 3 BP 937 EP 941 DI 10.1073/pnas.89.3.937 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HC385 UT WOS:A1992HC38500035 PM 1736309 ER PT J AU JOSHI, JB DAVE, HPG AF JOSHI, JB DAVE, HPG TI TRANSACTIVATION OF THE PROENKEPHALIN GENE PROMOTER BY THE TAX1 PROTEIN OF HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GLIOMA CELLS; ENKEPHALINS; TRANSFECTION; NEUROTRANSMITTER GENE EXPRESSION ID LONG TERMINAL REPEAT; PREPROENKEPHALIN MESSENGER-RNA; TROPICAL SPASTIC PARAPARESIS; LEUKEMIA-VIRUS; HTLV-I; REGULATORY SEQUENCES; EXPRESSION; ACTIVATION; INTERLEUKIN-2; TRANSCRIPTION AB Human T-cell lymphotropic virus type I (HTLV-I), an etiologic agent for adult T-cell leukemia, is strongly associated with certain neurological diseases. The HTLV-I genome encodes a protein, Tax1, that transactivates viral gene transcription. CD4-positive T helper lymphocytes express the proenkephalin gene, and enkephalins have been implicated as neuroimmunomodulators. We have investigated the effect of Tax1 on the proenkephalin gene promoter in C6 rat glioma cells and demonstrated its transactivation. Analysis using 5' deletion mutants of the promoter region showed that sequences upstream of base pair -190 are necessary for maximal transactivation. Forskolin, a cAMP modulator, synergistically increased Tax1-mediated transactivation of the proenkephalin promoter. Neither Tax1 transactivation alone nor Tax1/cAMP synergism exclusively involved cAMP-responsive elements. Endogenous proenkephalin gene expression increased in Tax1-expressing C6 cells. Since HTLV-I infects lymphocytes, which express proenkephalin mRNA, Tax1 transregulation of proenkephalin expression may provide bidirectional communication between the nervous and immune systems in HTLV-I-related diseases. C1 NHLBI, BIOCHEM GENET LAB, BETHESDA, MD 20892 USA. NIDDKD, CHEM BIOL LAB, BETHESDA, MD 20892 USA. NR 39 TC 20 Z9 20 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 1 PY 1992 VL 89 IS 3 BP 1006 EP 1010 DI 10.1073/pnas.89.3.1006 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HC385 UT WOS:A1992HC38500049 PM 1736281 ER PT J AU KRICKER, MC DRAKE, JW RADMAN, M AF KRICKER, MC DRAKE, JW RADMAN, M TI DUPLICATION-TARGETED DNA METHYLATION AND MUTAGENESIS IN THE EVOLUTION OF EUKARYOTIC CHROMOSOMES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE REPEAT-INDUCED POINT MUTATION; CPG DINUCLEOTIDE ID ESCHERICHIA-COLI; HOMOLOGOUS RECOMBINATION; PROCESSED PSEUDOGENES; MISMATCH-REPAIR; CPG ISLANDS; GENE FAMILY; SEQUENCE; CELLS; 5-METHYLCYTOSINE; MUTANTS AB Mammalian genomes are threatened with gene inactivation and chromosomal scrambling by recombination between repeated sequences such as mobile genetic elements and pseudogenes. We present and test a model for a defensive strategy based on the methylation and subsequent mutation of CpG dinucleotides in those DNA duplications that create uninterrupted homologous sequences longer than about 0.3 kilobases. The model helps to explain both the diversity of CpG frequencies in different genes and the persistence of gene fragmentation into exons and introns. C1 NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. INST JACQUES MONOD,F-75251 PARIS 05,FRANCE. NR 39 TC 133 Z9 135 U1 0 U2 0 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 1 PY 1992 VL 89 IS 3 BP 1075 EP 1079 DI 10.1073/pnas.89.3.1075 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HC385 UT WOS:A1992HC38500063 PM 1736289 ER PT J AU COE, JE ISHAK, KG WARD, JM ROSS, MJ AF COE, JE ISHAK, KG WARD, JM ROSS, MJ TI TAMOXIFEN PREVENTS INDUCTION OF HEPATIC NEOPLASIA BY ZERANOL, AN ESTROGENIC FOOD CONTAMINANT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ORAL-CONTRACEPTIVES; HEPATOCELLULAR-CARCINOMA; MALLORY BODIES; RAT-LIVER; ARMENIAN HAMSTER; FEMALE PROTEIN; CANCER; ZEARALENONE; RECEPTOR; MICE AB Zeranol (alpha-zearalanol) is a beta-resorcylic acid lactone (RAI,) that has estrogen activity. It is synthesized by molds and is difficult to avoid in human food products. We tested the ability of this mycoestrogen to damage the liver of the Armenian hamster, a rodent that is especially sensitive to hepatotoxic effects of exogenous estrogens. Zeranol induced acute hepatotoxicity and, subsequently, hepatic carcinogenesis; both effects were blocked by tamoxifen, suggesting estrogen receptor mediation. Because zeranol is acting alone as a primary initiator of hepatic neoplasms, this model provides an unusual opportunity to study the pathogenesis of estrogen-initiated tumorigenesis. C1 ARMED FORCES INST PATHOL,WASHINGTON,DC 20306. NCI,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RP COE, JE (reprint author), NIAID,PERSISTENT VIRAL DIS LAB,ROCKY MT LABS,HAMILTON,MT 59840, USA. NR 51 TC 30 Z9 31 U1 0 U2 1 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 1 PY 1992 VL 89 IS 3 BP 1085 EP 1089 DI 10.1073/pnas.89.3.1085 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HC385 UT WOS:A1992HC38500065 PM 1736291 ER PT J AU LOWREY, CH BODINE, DM NIENHUIS, AW AF LOWREY, CH BODINE, DM NIENHUIS, AW TI MECHANISM OF DNASE-I HYPERSENSITIVE SITE FORMATION WITHIN THE HUMAN GLOBIN LOCUS-CONTROL REGION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HEMOGLOBIN SWITCHING; CHROMATIN STRUCTURE; ERYTHROID SPECIFICITY; TRANSCRIPTION FACTOR GATA-1; TRANSCRIPTION FACTOR NF-E2 ID DOMINANT CONTROL REGION; DELTA-BETA-THALASSEMIA; HIGH-LEVEL EXPRESSION; CHROMATIN STRUCTURE; TRANSGENIC MICE; ERYTHROID-CELLS; GENE ACTIVATION; ENHANCER; DELETION; TRANSLOCATION AB The human beta-like globin gene locus contains embryonic, fetal, and adult globin genes that are regulated in a developmentally timed, as well as a tissue-specific, manner. The locus control region (LCR), located 5' of the globin genes, is characterized by four erythroid-specific nuclease-hypersensitive sites within native chromatin. These sites contain the active elements of the LCR. The LCR establishes an active chromatin conformation across the globin locus and enhances globin gene expression in transfected erythroleukemia cells and transgenic mice. We have used 5' DNase I hypersensitive site (HS) 4 as a model to define the minimum elements necessary for site formation. We have identified a 101-base-pair fragment within 5' HS4 that is the active site-forming clement. DNase I footprint and gel-mobility shift assays have identified binding sites for transcription factors AP-1/NF-E2, Sp-1, and GATA-1 within the HS-forming element. We conclude that HS formation, the characteristic feature of the 1,CR in nuclear chromatin, requires interaction between erythroid-specific and ubiquitous nuclear proteins. RP LOWREY, CH (reprint author), NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892, USA. NR 31 TC 74 Z9 74 U1 0 U2 1 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 1 PY 1992 VL 89 IS 3 BP 1143 EP 1147 DI 10.1073/pnas.89.3.1143 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HC385 UT WOS:A1992HC38500077 PM 1736298 ER PT J AU ADINOFF, B MEFFORD, I WAXMAN, R LINNOILA, M AF ADINOFF, B MEFFORD, I WAXMAN, R LINNOILA, M TI VAGAL TONE DECREASES FOLLOWING INTRAVENOUS DIAZEPAM SO PSYCHIATRY RESEARCH LA English DT Article DE BENZODIAZEPINE; NOREPINEPHRINE; AUTONOMIC NERVOUS SYSTEM; SINUS ARRHYTHMIA; HEART RATE ID AFFECTIVE-DISORDERS; NORMAL VOLUNTEERS; PLASMA; ACETYLCHOLINE; EPINEPHRINE; RESPONSES; DISEASE; HUMANS AB To investigate the relationship between anxiety and parasympathetic nervous system activity, cardiac vagal tone was assessed in six healthy volunteers after the intravenous administration of the anxiolytic diazepam. Vagal tone was determined by quantifying the amplitude of respiratory sinus arrhythmia. We observed a significant dose-dependent attenuation in vagal tone, accompanied by an increase in heart rate. There was a nonstatistically significant decrease in plasma norepinephrine concentrations and subjective anxiety ratings at higher doses of diazepam. We discuss a possible role of the parasympathetic nervous system in the anxiolytic effects of the benzodiazepines. C1 MED UNIV S CAROLINA,DEPT PSYCHIAT & BEHAV SCI,CHARLESTON,SC 29425. AMERICAN UNIV,WASHINGTON,DC 20016. NIMH,CLIN PHARMACOL & EXPTL THERAPEUT BRANCH,CLIN NEUROCHEM UNIT,BETHESDA,MD 20892. NIAAA,BETHESDA,MD. RP ADINOFF, B (reprint author), VET ADM MED CTR,CTR SUBST ABUSE TREATMENT,116A,109 BEE ST,CHARLESTON,SC 29403, USA. NR 32 TC 28 Z9 28 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD FEB PY 1992 VL 41 IS 2 BP 89 EP 97 DI 10.1016/0165-1781(92)90101-8 PG 9 WC Psychiatry SC Psychiatry GA HJ675 UT WOS:A1992HJ67500001 PM 1574544 ER PT J AU PAUL, IA TRULLAS, R SKOLNICK, P NOWAK, G AF PAUL, IA TRULLAS, R SKOLNICK, P NOWAK, G TI DOWN-REGULATION OF CORTICAL BETA-ADRENOCEPTORS BY CHRONIC TREATMENT WITH FUNCTIONAL NMDA ANTAGONISTS SO PSYCHOPHARMACOLOGY LA English DT Note DE BETA-ADRENOCEPTOR; ANTIDEPRESSANT; NMDA RECEPTOR; IMIPRAMINE; 1-AMINOCYCLOPROPANECARBOXYLIC ACID; MK-801 ID METHYL-D-ASPARTATE; RECEPTOR COMPLEX; RAT-BRAIN; RELEASE; GLYCINE; NOREPINEPHRINE; POTENT; MK-801; ACID; SITE AB Down-regulation of cortical beta-adrenoceptors is observed in laboratory animals following chronic treatment with many clinically effective antidepressant therapies. [H-3]Dihydroalprenolol (DHA) binding to cortical beta-adrenoceptors was examined in mice treated with the functional NMDA antagonists 1-aminocyclopropanecarboxylic acid (ACPC) and MK-801. ACPC and MK-801 reduced [H-3]DHA binding by 19 (P < 0.05) and 21% (P < 0.05), respectively, while imipramine produced a 23% (P < 0.05) reduction. No corresponding changes in the KD Of [H-3]DHA were observed. These findings are consistent with the observation that functional NMDA antagonists are active in animal models commonly used to evaluate antidepressants and may represent a novel approach to the treatment of depression. RP PAUL, IA (reprint author), NIDDKS,NEUROSCI LAB,BETHESDA,MD 20892, USA. RI Trullas, Ramon/D-2197-2016 OI Trullas, Ramon/0000-0001-7951-9881 NR 15 TC 67 Z9 69 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD FEB PY 1992 VL 106 IS 2 BP 285 EP 287 DI 10.1007/BF02801986 PG 3 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA HA248 UT WOS:A1992HA24800022 PM 1312732 ER PT J AU JOHNSON, LA HOPPEL, BE GERARD, EL MILLER, SPF DOPPELT, SH ZIRZOW, GC ROSENTHAL, DI DAMBROSIA, JM HILL, SC BRADY, RO ROSEN, BR BARTON, NW AF JOHNSON, LA HOPPEL, BE GERARD, EL MILLER, SPF DOPPELT, SH ZIRZOW, GC ROSENTHAL, DI DAMBROSIA, JM HILL, SC BRADY, RO ROSEN, BR BARTON, NW TI QUANTITATIVE CHEMICAL-SHIFT IMAGING OF VERTEBRAL BONE-MARROW IN PATIENTS WITH GAUCHER DISEASE SO RADIOLOGY LA English DT Article DE BONES, PRIMARY METABOLIC ABNORMALITIES; BONE MARROW, MR; GAUCHER DISEASE; MAGNETIC RESONANCE (MR), CHEMICAL SHIFT ID MAGNETIC-RESONANCE; PROTON; INVOLVEMENT; DISORDERS; CT AB To evaluate extent of bone marrow involvement and disease severity in Gaucher patients, results of modified Dixon quantitative chemical shift imaging (QCSI) of the lumbar spine were correlated with quantitative analysis of marrow triglycerides and glucocerebrosides and with quantitative determination of splenic volume at magnetic resonance (MR) imaging. High-field-strength MR spectra of surgical marrow specimens were dominated by a single fat and a water peak, validating use of QCSI. QCSI showed average vertebral marrow fat fractions of 10% +/- 8 in Gaucher patients (normal adult averages, 29% +/- 6). Relaxation times for lipid was water approximated normal averages; bulk T1 values were significantly longer, reflecting decreased marrow fat. Glucocerebroside concentrations were higher in Gaucher marrow and inversely correlated with triglyceride concentrations. Extent of marrow infiltration determined by fat fraction measurements correlated with disease severity measured by splenic enlargement. These results show that as Gaucher cells infiltrate bone marrow and displace normal marrow adipocytes, bulk T1 increases due to the higher T1 of water compared with that of fat. QCSI provides a sensitive, noninvasive technique for evaluating bone marrow involvement in Gaucher disease. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,CTR MGH NMR,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEPT ORTHOPED SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR AMBULATORY CARE,BOSTON,MA 02114. MIT,CAMBRIDGE,MA 02139. NINCDS,BETHESDA,MD 20892. NIH,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. FU NCI NIH HHS [R01-CA-40303] NR 39 TC 75 Z9 75 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 1992 VL 182 IS 2 BP 451 EP 455 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA HA586 UT WOS:A1992HA58600030 PM 1732964 ER PT J AU DUNNICK, NR BUSH, WH CHOYKE, PL FERNBACH, SK HARTMAN, DS RUBIN, JM SANDLER, CM WEBER, T AF DUNNICK, NR BUSH, WH CHOYKE, PL FERNBACH, SK HARTMAN, DS RUBIN, JM SANDLER, CM WEBER, T TI GENITOURINARY RADIOLOGY SO RADIOLOGY LA English DT Article DE KIDNEY, EFFECTS OF DRUGS ON; KIDNEY, MR; KIDNEY NEOPLASMS, DIAGNOSIS; PROSTATE, NEOPLASMS; RADIOLOGICAL-SOCIETY-OF-NORTH-AMERICA, 77TH SCIENTIFIC ASSEMBLY AND ANNUAL C1 UNIV WASHINGTON,MED CTR,SEATTLE,WA 98195. NIH,BETHESDA,MD 20892. CHILDRENS MEM HOSP,CHICAGO,IL 60614. PENN STATE UNIV,MILTON S HERSHEY MED CTR,HERSHEY,PA 17033. UNIV MICHIGAN,ANN ARBOR,MI 48109. UNIV TEXAS,SCH MED,HOUSTON,TX 77025. RP DUNNICK, NR (reprint author), DUKE UNIV,MED CTR,DURHAM,NC 27710, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD FEB PY 1992 VL 182 IS 2 BP 599 EP 602 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA HA586 UT WOS:A1992HA58600066 ER PT J AU THOMPSON, J DONKERSLOOT, JA AF THOMPSON, J DONKERSLOOT, JA TI BIOSYNTHESIS AND DISTRIBUTION OF N-CARBOXYALKYL AMINO-ACIDS (OPINES) IN BACTERIA SO RESEARCH IN MICROBIOLOGY LA English DT Article ID NOPALINE SYNTHASE GENE; STREPTOCOCCUS-LACTIS; T-DNA; NADP+ OXIDOREDUCTASE; CROWN GALL; OCTOPINE; PURIFICATION; SEQUENCE; REGION; N5-(L-1-CARBOXYETHYL)-L-ORNITHINE RP THOMPSON, J (reprint author), NIDR,MICROBIAL ECOL LAB,BETHESDA,MD 20892, USA. NR 31 TC 2 Z9 2 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0923-2508 J9 RES MICROBIOL JI Res. Microbiol. PD FEB PY 1992 VL 143 IS 2 BP 127 EP 131 DI 10.1016/0923-2508(92)90001-5 PG 5 WC Microbiology SC Microbiology GA HK343 UT WOS:A1992HK34300001 PM 1410788 ER PT J AU LIOTTA, LA AF LIOTTA, LA TI CANCER CELL INVASION AND METASTASIS SO SCIENTIFIC AMERICAN LA English DT Article C1 GEORGE WASHINGTON UNIV,SCH MED,WASHINGTON,DC 20052. RP LIOTTA, LA (reprint author), NCI,PATHOL LAB,BETHESDA,MD 20892, USA. NR 3 TC 170 Z9 180 U1 0 U2 4 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 SN 0036-8733 J9 SCI AM JI Sci.Am. PD FEB PY 1992 VL 266 IS 2 BP 54 EP & PG 0 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HA260 UT WOS:A1992HA26000010 PM 1373003 ER PT J AU CHESON, BD AF CHESON, BD TI CHEMOTHERAPY AND BONE-MARROW TRANSPLANTATION FOR MYELODYSPLASTIC SYNDROMES SO SEMINARS IN ONCOLOGY LA English DT Article ID DOSE CYTOSINE-ARABINOSIDE; ACUTE MYELOGENOUS LEUKEMIA; ACUTE NONLYMPHOBLASTIC LEUKEMIA; ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE MYELOBLASTIC-LEUKEMIA; THERAPY-RELATED LEUKEMIA; ACUTE MYELOID-LEUKEMIA; AGGRESSIVE CHEMOTHERAPY; INTENSIVE CHEMOTHERAPY; CELLS RP CHESON, BD (reprint author), NCI,MED SECT,CLIN INVEST BRANCH,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892, USA. NR 65 TC 23 Z9 23 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD FEB PY 1992 VL 19 IS 1 BP 85 EP 94 PG 10 WC Oncology SC Oncology GA HD449 UT WOS:A1992HD44900007 PM 1736371 ER PT J AU SHAYA, EK SCHEFFEL, U DANNALS, RF RICAURTE, GA CARROLL, FI WAGNER, HN KUHAR, MJ WONG, DF AF SHAYA, EK SCHEFFEL, U DANNALS, RF RICAURTE, GA CARROLL, FI WAGNER, HN KUHAR, MJ WONG, DF TI INVIVO IMAGING OF DOPAMINE REUPTAKE SITES IN THE PRIMATE BRAIN USING SINGLE PHOTON-EMISSION COMPUTED-TOMOGRAPHY (SPECT) AND I-123 LABELED RTI-55 SO SYNAPSE LA English DT Note DE DOPAMINE; REUPTAKE; MPTP; SPECT; I-123 ID PARKINSONS-DISEASE; COCAINE; SYSTEM; RECEPTORS; MPTP; PET; MONKEYS; ANALOGS; BINDING C1 JOHNS HOPKINS MED INST,DEPT NEUROL,BALTIMORE,MD 21205. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NIDA,ADDICT RES CTR,NEUROSCI BRANCH,BALTIMORE,MD 21224. RP SHAYA, EK (reprint author), JOHNS HOPKINS MED INST,DEPT RADIOL,BALTIMORE,MD 21205, USA. FU NCI NIH HHS [CA-32845]; NIDA NIH HHS [DA-06309]; NINDS NIH HHS [NS-15080] NR 23 TC 86 Z9 86 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD FEB PY 1992 VL 10 IS 2 BP 169 EP 172 DI 10.1002/syn.890100210 PG 4 WC Neurosciences SC Neurosciences & Neurology GA HB463 UT WOS:A1992HB46300009 PM 1585258 ER PT J AU GHANAYEM, BI SANCHEZ, IM MATTHEWS, HB AF GHANAYEM, BI SANCHEZ, IM MATTHEWS, HB TI DEVELOPMENT OF TOLERANCE TO 2-BUTOXYETHANOL-INDUCED HEMOLYTIC-ANEMIA AND STUDIES TO ELUCIDATE THE UNDERLYING MECHANISMS SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID GLYCOL MONOBUTYL ETHER; RATS; ERYTHROCYTES; METABOLISM; TOXICITY; AGE; DISPOSITION; INVITRO; CELL RP GHANAYEM, BI (reprint author), NIEHS,NATL TOXICOL PROGRAM,EXPTL TOXICOL BRANCH,RES TRIANGLE PK,NC 27709, USA. NR 18 TC 35 Z9 37 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD FEB PY 1992 VL 112 IS 2 BP 198 EP 206 DI 10.1016/0041-008X(92)90188-X PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA HF044 UT WOS:A1992HF04400005 PM 1539158 ER PT J AU BLAYLOCK, BL HOLLADAY, SD COMMENT, CE HEINDEL, JJ LUSTER, MI AF BLAYLOCK, BL HOLLADAY, SD COMMENT, CE HEINDEL, JJ LUSTER, MI TI EXPOSURE TO TETRACHLORODIBENZO-PARA-DIOXIN (TCDD) ALTERS FETAL THYMOCYTE MATURATION SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID T-CELL DEVELOPMENT; HALOGENATED AROMATIC-HYDROCARBONS; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN TCDD; LYMPHOCYTE SUBPOPULATIONS; IMMUNE-SYSTEM; THYMUS; MICE; EXPRESSION; SUPPRESSION; REARRANGEMENT C1 NIEHS,NATL TOXICOL PROGRAM,SYST TOXICOL BRANCH,DEV & REPROD TOXICOL GRP,RES TRIANGLE PK,NC 27709. N CAROLINA STATE UNIV,COLL VET MED,DEPT VET ANAT PHYSIOL SCI & RADIOL,RALEIGH,NC 27606. RP BLAYLOCK, BL (reprint author), NIEHS,NATL TOXICOL PROGRAM,SYST TOXICOL BRANCH,IMMUNOTOXICOL GRP,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 32 TC 82 Z9 84 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD FEB PY 1992 VL 112 IS 2 BP 207 EP 213 DI 10.1016/0041-008X(92)90189-Y PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA HF044 UT WOS:A1992HF04400006 PM 1531708 ER PT J AU ROSENTHAL, GJ CRAIG, WA CORSINI, E TAYLOR, M LUSTER, MI AF ROSENTHAL, GJ CRAIG, WA CORSINI, E TAYLOR, M LUSTER, MI TI PENTAMIDINE BLOCKS THE PATHOPHYSIOLOGIC EFFECTS OF ENDOTOXEMIA THROUGH INHIBITION OF CYTOKINE RELEASE SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID TUMOR NECROSIS FACTOR; PNEUMOCYSTIS-CARINII PNEUMONIA; FACTOR-ALPHA; MECHANISMS; CACHECTIN; MACROPHAGES; EXPRESSION; CELLS C1 UNIV MILAN,INST PHARMACOL SCI,I-20122 MILAN,ITALY. RP ROSENTHAL, GJ (reprint author), NIEHS,NATL TOXICOL PROGRAM,SYST TOXIC BRANCH,IMMUNOTOXICOL SECT,RES TRIANGLE PK,NC 27709, USA. RI Corsini, Emanuela/B-5602-2011 NR 26 TC 13 Z9 13 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD FEB PY 1992 VL 112 IS 2 BP 222 EP 228 DI 10.1016/0041-008X(92)90191-T PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA HF044 UT WOS:A1992HF04400008 PM 1539159 ER PT J AU SMITH, CV NAKAJIMA, K MIXON, A GUZZETTA, PC ROSENGARD, BR FISHBEIN, JM SACHS, DH AF SMITH, CV NAKAJIMA, K MIXON, A GUZZETTA, PC ROSENGARD, BR FISHBEIN, JM SACHS, DH TI SUCCESSFUL INDUCTION OF LONG-TERM SPECIFIC TOLERANCE TO FULLY ALLOGENEIC RENAL-ALLOGRAFTS IN MINIATURE SWINE SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 17TH ANNUAL MEETING OF THE AMERICAN SOC OF TRANSPLANT SURGEONS CY MAY 29-31, 1991 CL CHICAGO, IL SP AMER SOC TRANSPLANT SURGEONS ID BONE-MARROW TRANSPLANTATION; CLASS-II GENES; MAJOR HISTOCOMPATIBILITY COMPLEX; POSTTRANSPLANT ANTITHYMOCYTE GLOBULIN; RHESUS-MONKEYS; IMMUNOLOGICAL-UNRESPONSIVENESS; SKIN ALLOGRAFTS; INJECTED MICE; MHC ANTIGENS; SURVIVAL AB Major histocompatibility complex class II matching is of overwhelming importance for achieving tolerance to kidney transplants (KTX) in miniature swine. When class II antigens are matched, long-term specific tolerance across complete MHC class I antigen barriers can uniformly be induced by a 12-day perioperative course of cyclosporine. This same regimen is ineffective in fully MHC-mismatched combinations. We hypothesized that initial induction of tolerance to kidney donor class II antigens by bone marrow transplantation might allow tolerance to be induced to a subsequent fully allogeneic KTX in combination with CsA therapy. We report here the results of such fully allogeneic KTX performed in 4 recipients of prior single-haplotype class II-mismatched BMT. All animals received KTX from donors class II matched to the BMT donor and received a 12-day course of intravenous CsA (10 mg/kg/day). All four animals have maintained normal serum creatinine values (less than 2.0 mg/dl) for greater than 200 days posttransplant. Specific hyporesponsiveness to both BMT and KTX donor-type MHC antigens was found in mixed lymphocyte culture and cell-mediated lympholysis assays. Compared with third-party grafts, significantly prolonged survival of BMT donor-specific (P = 0.031) and KTX donor-specific (P = 0.031) skin grafts was observed. These results demonstrate that induction of tolerance to class II antigens by BMT allows a short course of CsA to induce specific tolerance to fully allogeneic renal allografts. C1 NCI,IMMUNOL BRANCH,TRANSPLANTAT BIOL SECT,BETHESDA,MD 20892. RP SMITH, CV (reprint author), MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,MGH E,BLDG 149,13TH ST,BOSTON,MA 02114, USA. NR 51 TC 33 Z9 33 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD FEB PY 1992 VL 53 IS 2 BP 438 EP 444 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA HD765 UT WOS:A1992HD76500033 PM 1531395 ER PT J AU HOCHGESCHWENDER, U AF HOCHGESCHWENDER, U TI TOWARD A TRANSCRIPTIONAL MAP OF THE HUMAN GENOME SO TRENDS IN GENETICS LA English DT Note ID TRANSCRIBED SEQUENCES; DNA; GENE; CONSTRUCTION; LIBRARIES; CDNAS RP HOCHGESCHWENDER, U (reprint author), NIMH,CLIN NEUROGENET BRANCH,GENOM UNIT,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 24 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD FEB PY 1992 VL 8 IS 2 BP 41 EP 44 DI 10.1016/0168-9525(92)90030-8 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA HB952 UT WOS:A1992HB95200001 PM 1566368 ER PT J AU STATES, DJ AF STATES, DJ TI MOLECULAR SEQUENCE ACCURACY - ANALYZING IMPERFECT DATA SO TRENDS IN GENETICS LA English DT Article ID DNA; ALIGNMENT; CLONES AB Molecular sequences are experimentally derived data that can be expected to contain errors as a result of diverse phenomena such as biological variation, molecular cloning artifacts, imperfect sequence determination, and data bandling during contig assembly. Errors will affect the reliability of database searches and sequence alignments, but their impact may be minimized by the use of analytical techniques that anticipate that the data will be imperfect. RP STATES, DJ (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BLDG 38A,ROOM 8S806,BETHESDA,MD 20894, USA. NR 17 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD FEB PY 1992 VL 8 IS 2 BP 52 EP 55 DI 10.1016/0168-9525(92)90043-4 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA HB952 UT WOS:A1992HB95200006 PM 1566371 ER PT J AU BONNER, TI AF BONNER, TI TI DOMAINS OF MUSCARINIC ACETYLCHOLINE-RECEPTORS THAT CONFER SPECIFICITY OF G-PROTEIN COUPLING SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Article ID BETA-ADRENERGIC-RECEPTOR; LIGAND-BINDING; DELINEATION RP BONNER, TI (reprint author), NIMH,CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 11 TC 48 Z9 48 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD FEB PY 1992 VL 13 IS 2 BP 48 EP 50 DI 10.1016/0165-6147(92)90021-W PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HD766 UT WOS:A1992HD76600003 PM 1561711 ER PT J AU RASMUSSEN, L GREENWOOD, JD GONDA, MA AF RASMUSSEN, L GREENWOOD, JD GONDA, MA TI EXPRESSION OF BOVINE IMMUNODEFICIENCY-LIKE VIRUS ENVELOPE GLYCOPROTEINS BY A RECOMBINANT BACULOVIRUS IN INSECT CELLS SO VIROLOGY LA English DT Article ID BIOLOGICALLY-ACTIVE PROVIRUSES; INFECTIOUS-ANEMIA VIRUS; OLIGOMERIC STRUCTURE; VISNA VIRUS; INFLUENZA HEMAGGLUTININ; INTRACELLULAR-TRANSPORT; NUCLEOTIDE-SEQUENCE; GENOME ORGANIZATION; MOLECULAR-CLONING; ENV EXPRESSION C1 DYNCORP,NCI,FREDERICK CANC RES & DEV CTR,CELL & MOLEC STRUCT LAB,PROGRAM RESOURCES,POB B,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74102] NR 51 TC 19 Z9 19 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD FEB PY 1992 VL 186 IS 2 BP 551 EP 561 DI 10.1016/0042-6822(92)90021-G PG 11 WC Virology SC Virology GA GZ516 UT WOS:A1992GZ51600021 PM 1310184 ER PT J AU SATO, H ORENSTEIN, J DIMITROV, D MARTIN, M AF SATO, H ORENSTEIN, J DIMITROV, D MARTIN, M TI CELL-TO-CELL SPREAD OF HIV-1 OCCURS WITHIN MINUTES AND MAY NOT INVOLVE THE PARTICIPATION OF VIRUS-PARTICLES SO VIROLOGY LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; DNA POLYMERASE-ALPHA; HTLV-III LAV; DEXTRAN SULFATE; INVITRO; INFECTION; REPLICATION; GLYCOPROTEIN; APHIDICOLIN; FUSION C1 GEORGE WASHINGTON UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20036. NCI,MATH BIOL LAB,BETHESDA,MD 20892. RP SATO, H (reprint author), NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892, USA. NR 51 TC 196 Z9 199 U1 2 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD FEB PY 1992 VL 186 IS 2 BP 712 EP 724 DI 10.1016/0042-6822(92)90038-Q PG 13 WC Virology SC Virology GA GZ516 UT WOS:A1992GZ51600038 PM 1370739 ER PT J AU BOSSELUT, R LIM, F ROMOND, PC FRAMPTON, J BRADY, J GHYSDAEL, J AF BOSSELUT, R LIM, F ROMOND, PC FRAMPTON, J BRADY, J GHYSDAEL, J TI MYB PROTEIN BINDS TO MULTIPLE SITES IN THE HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-1 LONG TERMINAL REPEAT AND TRANSACTIVATES LTR-MEDIATED EXPRESSION SO VIROLOGY LA English DT Note ID TRANSCRIPTIONAL CONTROL REGION; ENCODING NUCLEAR PROTEINS; NORMAL HUMAN-LYMPHOCYTES; I-ASSOCIATED MYELOPATHY; ONCOGENE-C-MYB; CDNA CLONES; V-MYB; NUCLEOTIDE-SEQUENCE; LEUKEMIA PATIENTS; TRANS-ACTIVATION C1 EUROPEAN MOLEC BIOL LAB,DIFFERENTIAT PROGRAM,W-6900 HEIDELBERG,GERMANY. NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. RP BOSSELUT, R (reprint author), CTR UNIV ORSAY,INST CURIE,ONCOL VIRALE & CELLULAIRE LAB,CNRS,URA 1443,F-91405 ORSAY,FRANCE. RI Lim, Filip/C-7412-2011; GHYSDAEL, Jacques/F-3377-2013 OI Lim, Filip/0000-0001-6570-1017; NR 47 TC 43 Z9 43 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD FEB PY 1992 VL 186 IS 2 BP 764 EP 769 DI 10.1016/0042-6822(92)90044-P PG 6 WC Virology SC Virology GA GZ516 UT WOS:A1992GZ51600044 PM 1733110 ER PT J AU AMEGADZIE, BY SISLER, JR MOSS, B AF AMEGADZIE, BY SISLER, JR MOSS, B TI FRAME-SHIFT MUTATIONS WITHIN THE VACCINIA VIRUS A-TYPE INCLUSION PROTEIN GENE SO VIROLOGY LA English DT Note ID MESSENGER-RNAS; COWPOX VIRUS; POLY(A) SEQUENCES; MAJOR PROTEIN; POLYMERASE; SUBUNIT; LEADER C1 NIAID,VIRAL DIS LAB,BLDG 4,ROOM 229,BETHESDA,MD 20892. NR 20 TC 37 Z9 38 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD FEB PY 1992 VL 186 IS 2 BP 777 EP 782 DI 10.1016/0042-6822(92)90046-R PG 6 WC Virology SC Virology GA GZ516 UT WOS:A1992GZ51600046 PM 1733111 ER PT J AU NOVEMBRE, FJ HIRSCH, VM MCCLURE, HM FULTZ, PN JOHNSON, PR AF NOVEMBRE, FJ HIRSCH, VM MCCLURE, HM FULTZ, PN JOHNSON, PR TI SIV FROM STUMP-TAILED MACAQUES - MOLECULAR CHARACTERIZATION OF A HIGHLY TRANSMISSIBLE PRIMATE LENTIVIRUS SO VIROLOGY LA English DT Note ID SIMIAN IMMUNODEFICIENCY VIRUS; SEROEPIDEMIOLOGIC SURVEY; CERCOCEBUS-ATYS; RETROVIRUS; MONKEYS; ANTIBODIES; PREVALENCE; MANGABEYS C1 GEORGETOWN UNIV,DEPT MICROBIOL,DIV MOLEC VIROL & IMMUNOL,RETROVIRAL PATHOGENESIS SECT,ROCKVILLE,MD 20852. NIAID,INFECT DIS LAB,ROCKVILLE,MD 20852. YERKES REG PRIMATE RES CTR,DIV PATHOBIOL & IMMUNOL,ATLANTA,GA 30322. EMORY UNIV,DEPT PATHOL,ATLANTA,GA 30322. RI Johnson, Philip/A-6892-2009 FU NCRR NIH HHS [RR-00165]; NIAID NIH HHS [N01-AI-772623] NR 22 TC 43 Z9 43 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD FEB PY 1992 VL 186 IS 2 BP 783 EP 787 DI 10.1016/0042-6822(92)90047-S PG 5 WC Virology SC Virology GA GZ516 UT WOS:A1992GZ51600047 PM 1733112 ER PT J AU MARGOLIS, DM RABSON, AB STRAUS, SE OSTROVE, JM AF MARGOLIS, DM RABSON, AB STRAUS, SE OSTROVE, JM TI TRANSACTIVATION OF THE HIV-1 LTR BY HSV-1 IMMEDIATE-EARLY GENES SO VIROLOGY LA English DT Note ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; TUMOR NECROSIS FACTOR; TRANSCRIPTIONAL REGULATION; KAPPA-B; T-CELLS; ACTIVATES TRANSCRIPTION; TRANS-ACTIVATION; MESSENGER-RNA; TYPE-1 C1 NIAID,CLIN INVEST LAB,MED VIROL SECT,BLDG 10,RM 11N-228,BETHESDA,MD 20892. ROBERT WOODS JOHNSON MED SCH,CTR ADV BIOTECHNOL & MED,PISCATAWAY,NJ 08854. MICROBIOL ASSOCIATES INC,ROCKVILLE,MD 20805. OI Margolis, David/0000-0001-5714-0002 NR 33 TC 71 Z9 72 U1 1 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD FEB PY 1992 VL 186 IS 2 BP 788 EP 791 DI 10.1016/0042-6822(92)90048-T PG 4 WC Virology SC Virology GA GZ516 UT WOS:A1992GZ51600048 PM 1310199 ER PT J AU AAMODT, RL COON, JS DEITCH, A WHITE, RWD KOSS, LG MELAMED, MR WEINSTEIN, RS WHEELESS, LL AF AAMODT, RL COON, JS DEITCH, A WHITE, RWD KOSS, LG MELAMED, MR WEINSTEIN, RS WHEELESS, LL TI FLOW CYTOMETRIC EVALUATION OF BLADDER-CANCER - RECOMMENDATIONS OF THE NCI FLOW-CYTOMETRY NETWORK FOR BLADDER-CANCER SO WORLD JOURNAL OF UROLOGY LA English DT Article ID SENSITIVITY; VARIABILITY; EXPERIENCE; CARCINOMA; CYTOLOGY; SAMPLES AB The National Cancer Institute-supported Flow Cytometry Network for Bladder Cancer concluded that when properly used, DNA flow cytometry of bladder irrigation specimens can be a clinically useful laboratory procedure to monitor patients with bladder cancer. It recommended the use of this technique in managing patients with low-stage disease, particularly flat carcinoma in situ. The method has limited value in managing patients with high-stage (i.e., muscle-invasive) carcinoma; it is not recommended for screening subjects in the absence of a clinical suspicion of or a history of bladder tumors. DNA histograms alone are not sufficient for diagnosis or clinical action but require correlation with other clinical information. Bladder irrigation specimens collected during cystoscopy or by vigorous barbotage via a number 18 Foley catheter may be processed for flow cytometric analyses. Criteria for sampling adequacy have been established and are presented in this report. Optimal results are obtained with fresh specimens that are stained and examined promptly after collection. Preservation procedures are described for cases in which fresh specimens cannot be evaluated. Used with appropriate quality-control measures, commercially available flow cytometers can provide clinically useful information. Staining protocols using propidium iodide are recommended by the Network. Staining protocols are described for isolated nuclei and whole cells (see Appendix). The presence of bladder cancer is signaled by the identification of cell populations with clearly aneuploid DNA content. Quality-control measures and issues of inter- and intralaboratory differences in histogram configuration and analysis must be considered in the interpretation of results. Although the Network participants recognize the potential value of additional markers, these were not evaluated. C1 RUSH PRESBYTERIAN ST LUKES MED CTR,DEPT PATHOL,CHICAGO,IL 60612. MONTEFIORE MED CTR,DEPT PATHOL,NEW YORK,NY 10467. UNIV ROCHESTER,DEPT PATHOL & LAB MED,ROCHESTER,NY 14642. UNIV CALIF DAVIS,SACRAMENTO MED CTR,DEPT UROL,SACRAMENTO,CA 95817. UNIV ARIZONA,DEPT PATHOL,TUCSON,AZ 85724. MEM SLOAN KETTERING CANC CTR,DEPT PATHOL,NEW YORK,NY 10021. RP AAMODT, RL (reprint author), NCI,CANC DIAG BRANCH,DIV CANC BIOL DIAG & CTR,ROCKVILLE,MD 20892, USA. NR 12 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0724-4983 J9 WORLD J UROL JI World J. Urol. PD FEB PY 1992 VL 10 IS 1 BP 63 EP 67 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA HG047 UT WOS:A1992HG04700014 ER PT J AU MAHER, F VANNUCCI, S TAKEDA, J SIMPSON, IA AF MAHER, F VANNUCCI, S TAKEDA, J SIMPSON, IA TI EXPRESSION OF MOUSE-GLUT3 AND HUMAN-GLUT3 GLUCOSE TRANSPORTER PROTEINS IN BRAIN SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID LOCALIZATION; MUSCLE C1 UNIV CHICAGO,HOWARD HUGHES MED INST,CHICAGO,IL 60637. RP MAHER, F (reprint author), NIDDK,DIABETES BRANCH,EXPTL DIABETES METAB & NUTR SECT,BLDG 10,ROOM 5N102,BETHESDA,MD 20892, USA. NR 17 TC 114 Z9 116 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 31 PY 1992 VL 182 IS 2 BP 703 EP 711 DI 10.1016/0006-291X(92)91789-S PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA HC397 UT WOS:A1992HC39700040 PM 1734877 ER PT J AU KUTTY, RK FLETCHER, RT CHADER, GJ KRISHNA, G AF KUTTY, RK FLETCHER, RT CHADER, GJ KRISHNA, G TI EXPRESSION OF GUANYLATE CYCLASE-A MESSENGER-RNA IN THE RAT RETINA - DETECTION USING POLYMERASE CHAIN-REACTION SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ATRIAL-NATRIURETIC-PEPTIDE; ROD OUTER SEGMENTS; STRANDED-DNA; RECEPTOR; FORM C1 NEI,RETINAL CELL BIOL & MOLEC BIOL,BETHESDA,MD 20892. RP KUTTY, RK (reprint author), NHLBI,DRUG TISSUE INTERACT SECT,CHEM PHARMACOL LAB,BETHESDA,MD 20892, USA. NR 23 TC 35 Z9 35 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 31 PY 1992 VL 182 IS 2 BP 851 EP 857 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA HC397 UT WOS:A1992HC39700061 PM 1370893 ER PT J AU CHANDLER, MJ HOBBS, SF FU, QG KENSHALO, DR BLAIR, RW FOREMAN, RD AF CHANDLER, MJ HOBBS, SF FU, QG KENSHALO, DR BLAIR, RW FOREMAN, RD TI RESPONSES OF NEURONS IN VENTROPOSTEROLATERAL NUCLEUS OF PRIMATE THALAMUS TO URINARY-BLADDER DISTENSION SO BRAIN RESEARCH LA English DT Article DE VISCERAL AFFERENT; SOMATIC AFFERENT; NOCICEPTION; SPINOTHALAMIC TRACT; THALAMOCORTICAL NEURON ID POSTERIOR LATERAL NUCLEUS; VENTRALIS POSTEROLATERALIS; SPINOTHALAMIC TRACT; AFFERENT INPUT; CAT THALAMUS; SPINAL-CORD; MONKEY; STIMULATION; PATHWAYS; BRAIN AB The purpose of this study was to examine effects of a noxious visceral stimulus, urinary bladder distension (UBD), on cells in the ventroposterolateral (VPL) nucleus of anesthetized monkeys. We hypothesized that processing of visceral information in the VPL nucleus of the thalamus is similar to spinothalamic tract (STT) organization of visceral afferent input. Urinary bladder distension excites sacral and upper-lumbar STT cells that have somatic input from proximal somatic fields 25; whereas, thoracic STT cells are inhibited by UBD7. Extracellular action potentials of 67 neurons were recorded in VPL nucleus. Urinary bladder distension excited 22 cells, inhibited 9 cells, and did not affect activity of 36 cells. Seventeen of 22 cells excited by UBD also received convergent somatic input from noxious squeeze of the hip, groin, or perineal regions. No cells activated only by innocuous somatic stimuli were excited by UBD. Five of 9 cells inhibited by UBD had upper-body somatic fields. There was a significant tendency for VPL neurons excited by UBD to have proximal lower-body somatic fields that were excited by noxious stimulation of skin and underlying muscle (P < 0.001). Antidromic activation of 4 thalamic neurons affected by UBD showed that visceral input stimulated by UBD reached the primary somatosensory (SI) cortex. C1 NIDR,BETHESDA,MD 20205. RP CHANDLER, MJ (reprint author), UNIV OKLAHOMA,HLTH SCI CTR,DEPT PHYSIOL & BIOPHYS,POB 26901,OKLAHOMA CITY,OK 73190, USA. FU NHLBI NIH HHS [HL22732] NR 34 TC 55 Z9 56 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 31 PY 1992 VL 571 IS 1 BP 26 EP 34 DI 10.1016/0006-8993(92)90506-5 PG 9 WC Neurosciences SC Neurosciences & Neurology GA HC776 UT WOS:A1992HC77600003 PM 1611493 ER PT J AU CHIN, GJ GOLDMAN, SA AF CHIN, GJ GOLDMAN, SA TI PURIFICATION OF SQUID SYNAPTIC VESICLES AND CHARACTERIZATION OF THE VESICLE-ASSOCIATED PROTEINS SYNAPTOBREVIN AND RAB3A SO BRAIN RESEARCH LA English DT Article DE SYNAPTOBREVIN; RAB3; SYNAPTIC VESICLE; GIANT AXON; GIANT SYNAPSE; GTP-BINDING PROTEIN; SQUID; EXOCYTOSIS ID INTEGRAL MEMBRANE-PROTEIN; GTP-BINDING PROTEINS; GIANT SYNAPSE; PLASMA-MEMBRANE; RAT-BRAIN; APLYSIA; SYNAPTOSOMES; TRANSPORT; RELEASE AB Two proteins associated with mammalian synaptic vesicles, the integral membrane protein synaptobrevin and the GTP-binding protein rab3A, are identified in squid nervous tissue using Western blotting and subcellular fractionation of synaptosomes. They both copurify with synaptic vesicles prepared from squid optic lobe. Synaptobrevin (18.1 kDa) is present at high levels in synaptic terminals but at very low levels in axon. Rab3A (27.5 kDa) is a member of the rab family of low-molecular weight GTP-binding proteins which regulates vesicle traffic in secretory and endocytic processes. As resolved with 2-dimensional gels, squid neurons contain at least 16 GTP-binding species (19-29 kDa), and most of these are present in both soluble and particulate fractions. The 24 kDa class of GTP-binding proteins is highly enriched in axonal transport organelles. The characterization of synaptobrevin and rab3A in squid synaptic vesicles extends their known distributions to invertebrates and points to a fundamental importance of these proteins in neurotransmitter release. RP CHIN, GJ (reprint author), NICHHD,DEV NEUROBIOL LAB,BLDG 36,RM B-318,BETHESDA,MD 20892, USA. NR 33 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 31 PY 1992 VL 571 IS 1 BP 89 EP 96 DI 10.1016/0006-8993(92)90512-8 PG 8 WC Neurosciences SC Neurosciences & Neurology GA HC776 UT WOS:A1992HC77600009 PM 1319264 ER PT J AU WICKNER, S AF WICKNER, S TI DNA-REPLICATION, 2ND EDITION - KORNBERG,A, BAKER,T SO NATURE LA English DT Book Review RP WICKNER, S (reprint author), NIH,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JAN 30 PY 1992 VL 355 IS 6359 BP 406 EP 407 DI 10.1038/355406b0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HB530 UT WOS:A1992HB53000050 ER PT J AU LARRALDE, H TRUNFIO, P HAVLIN, S STANLEY, HE WEISS, GH AF LARRALDE, H TRUNFIO, P HAVLIN, S STANLEY, HE WEISS, GH TI TERRITORY COVERED BY N DIFFUSING PARTICLES SO NATURE LA English DT Article ID DISORDERED MEDIA; LATTICES AB THE number of distinct sites visited by a random walker after t steps is of great interest 1-21, as it provides a direct measure of the territory covered by a diffusing particle. Thus, this quantity appears in the description of many phenomena of interest in ecology 13-16, metallurgy 5-7, chemistry 17,18 and physics 19-22. Previous analyses have been limited to the number of distinct sites visited by a single random walker 19-22, but the (nontrivial) generalization to the number of distinct sites visited by N walkers is particularly relevant to a range of problems-for example, the classic problem in mathematical ecology of defining the territory covered by N members of a given species 13-16. Here we present an analytical solution to the problem of calculating S(N)(t), the mean number of distinct sites visited by N random walkers on a d-dimensional lattice, for d = 1, 2, 3 in the limit of large N. We confirm the analytical arguments by Monte Carlo and exact enumeration methods. We find that there are three distinct time regimes, and we determine SN(t) in each regime. Moreover, we also find a remarkable transition, for dimensions greater-than-or-equal-to 2, in the geometry of the set of visited sites. This set initially grows as a disk with a relatively smooth surface until it reaches a certain size, after which the surface becomes increasingly rough. C1 BOSTON UNIV, DEPT PHYS, BOSTON, MA 02215 USA. NIH, DIV COMP RES & TECHNOL, PHYS SCI LAB, BETHESDA, MD 20892 USA. RP BOSTON UNIV, CTR POLYMER STUDIES, BOSTON, MA 02215 USA. NR 25 TC 87 Z9 87 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD JAN 30 PY 1992 VL 355 IS 6359 BP 423 EP 426 DI 10.1038/355423a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HB530 UT WOS:A1992HB53000060 ER PT J AU LUDLOW, CL HALLETT, M RHEW, K COLE, R SHIMIZU, T SAKAGUCHI, G BAGLEY, JA SCHULZ, GM YIN, SG KODA, J AF LUDLOW, CL HALLETT, M RHEW, K COLE, R SHIMIZU, T SAKAGUCHI, G BAGLEY, JA SCHULZ, GM YIN, SG KODA, J TI THERAPEUTIC USE OF TYPE-F BOTULINUM TOXIN SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID HEMIFACIAL SPASM; FOCAL DYSTONIAS; INJECTIONS C1 NINCDS,BETHESDA,MD 20892. CHIBA SERUM INST,CHIBA,JAPAN. UNIV OSAKA PREFECTURE,COLL AGR,SAKAI,OSAKA 591,JAPAN. RP LUDLOW, CL (reprint author), NIDOCD,BETHESDA,MD 20892, USA. OI Ludlow, Christy/0000-0002-2015-6171 NR 11 TC 69 Z9 70 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 30 PY 1992 VL 326 IS 5 BP 349 EP 350 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA HA991 UT WOS:A1992HA99100027 PM 1728750 ER PT J AU FREEDMAN, LS GRAUBARD, BI SCHATZKIN, A AF FREEDMAN, LS GRAUBARD, BI SCHATZKIN, A TI STATISTICAL VALIDATION OF INTERMEDIATE END-POINTS FOR CHRONIC DISEASES SO STATISTICS IN MEDICINE LA English DT Article ID SURROGATE ENDPOINTS; CLINICAL-TRIALS; CANCER AB We discuss the implementation of a criterion due to Prentice for the statistical validation of intermediate endpoints for chronic disease. The criterion involves examining in a cohort or intervention study whether an exposure or intervention effect, adjusted for the intermediate endpoint, is reduced to zero. For example, to examine whether serum cholesterol level is an intermediate endpoint for coronary heart disease (CHD), we may investigate the effect of the cholesterol lowering drug cholestyramine on CHD incidence adjusted for serum cholesterol levels. We show that use of this criterion will usually demand some form of model selection. When the unadjusted exposure or treatment effect is less than four times its standard error, the analysis can usually lead only to a weak form of validation, a conclusion that the data are not inconsistent with the validation criterion. More significant unadjusted exposure effects offer the potential for stronger types of validation statement such as 'the intermediate endpoint explains at least 50 per cent (or 75 per cent) of the exposure effect'. C1 NCI,DIV CANC PREVENT & CONTROL,CANC PREVENT STUDIES BRANCH,BETHESDA,MD 20892. RP FREEDMAN, LS (reprint author), NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,BETHESDA,MD 20892, USA. NR 14 TC 386 Z9 388 U1 1 U2 10 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 30 PY 1992 VL 11 IS 2 BP 167 EP 178 DI 10.1002/sim.4780110204 PG 12 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA HH267 UT WOS:A1992HH26700003 PM 1579756 ER PT J AU LAKATOS, E LAN, KKG AF LAKATOS, E LAN, KKG TI A COMPARISON OF SAMPLE-SIZE METHODS FOR THE LOGRANK STATISTIC SO STATISTICS IN MEDICINE LA English DT Article ID CLINICAL-TRIALS; LOG-RANK; FOLLOW-UP; SURVIVAL; NONCOMPLIANCE; DURATION; LOSSES; POWER; TESTS AB Several methods are available for sample size calculation for clinical trials when survival curves are to be compared using the logrank statistic. We discuss advantages and disadvantages of some of these methods, and present simulation results under exponential, proportional hazards and non-proportional hazard situations. C1 GEORGE WASHINGTON UNIV,DEPT STAT COMP & INFORMAT SYST,WASHINGTON,DC 20052. RP LAKATOS, E (reprint author), NHLBI,BIOSTAT RES BRANCH,BETHESDA,MD 20892, USA. NR 22 TC 47 Z9 50 U1 2 U2 10 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 30 PY 1992 VL 11 IS 2 BP 179 EP 191 DI 10.1002/sim.4780110205 PG 13 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA HH267 UT WOS:A1992HH26700004 PM 1579757 ER PT J AU SEIGEL, D AF SEIGEL, D TI SAMPLE SIZES FOR CONSTRUCTING CONFIDENCE-INTERVALS AND TESTING HYPOTHESES SO STATISTICS IN MEDICINE LA English DT Letter RP SEIGEL, D (reprint author), NEI,BIOMETRY & EPIDEMIOL PROGRAM,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 1 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 30 PY 1992 VL 11 IS 2 BP 269 EP 269 DI 10.1002/sim.4780110212 PG 1 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA HH267 UT WOS:A1992HH26700011 PM 1579763 ER PT J AU CHEN, TT AF CHEN, TT TI A REVIEW OF METHODS FOR MISCLASSIFIED CATEGORICAL-DATA IN EPIDEMIOLOGY - REPLY SO STATISTICS IN MEDICINE LA English DT Letter ID SAMPLING SCHEMES; ERRORS RP CHEN, TT (reprint author), NCI,BIOMETR RES BRANCH,BETHESDA,MD 20892, USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 30 PY 1992 VL 11 IS 2 BP 272 EP 275 PG 4 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA HH267 UT WOS:A1992HH26700015 ER PT J AU TENG, K MARQUEZ, VE MILNE, GWA BARCHI, JJ KAZANIETZ, MG LEWIN, NE BLUMBERG, PM ABUSHANAB, E AF TENG, K MARQUEZ, VE MILNE, GWA BARCHI, JJ KAZANIETZ, MG LEWIN, NE BLUMBERG, PM ABUSHANAB, E TI CONFORMATIONALLY CONSTRAINED ANALOGS OF DIACYLGLYCEROL - INTERACTION OF GAMMA-LACTONES WITH THE PHORBOL ESTER RECEPTOR OF PROTEIN-KINASE-C SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID MOUSE-BRAIN CYTOSOL; D-ISOASCORBIC ACIDS; TUMOR PROMOTERS; CALCIUM MOBILIZATION; SIGNAL TRANSDUCTION; PLATELET ACTIVATION; 2ND MESSENGERS; BINDING; GROWTH; PHOSPHORYLATION AB Four 2-deoxy-erythro-1,4-lactones in the D- and L-series and the four corresponding 2-deoxy-threo-1,4-lactones, bearing myristic acid acyl groups at either primary or secondary alcohol functions, were synthesized from L-ascorbic and D-isoascorbic acids. These eight pentonolactones which represent all possible isomers in this series were designed as rigid analogues of 1,2-diacylglycerol (DAG). The inhibition by these compounds of the binding of [H-3]phorbol-12,13-dibutyrate to protein kinase C (PK-C) demonstrated the importance in this context of stereochemistry and particularly of the orientation of the fatty acid side chain. The most effective inhibitor (13d, K(i) = 2.3-mu-M) has a fixed conformation which is presumed to be similar to the conformation adopted by DAG when binding to PK-C. A three-point attachment model which has been previously used to rationalize the similar behavior of DAG and phorbol esters was extended to include additional points of equivalence between these two PK-C agonists. This extended model addresses the disposition of the lipophilic myristic acid side chain and the orientation of the lactone carbonyl group which functions as a hydrogen bond acceptor. In this new model, the most active isomer 13d provides the best fit of the eight pentonolactones to phorbol myristate acetate. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. UNIV RHODE ISL,DEPT MED CHEM,KINGSTON,RI 02881. UNIV RHODE ISL,DEPT CHEM,KINGSTON,RI 02881. RI Barchi Jr., Joseph/N-3784-2014 NR 54 TC 60 Z9 60 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JAN 29 PY 1992 VL 114 IS 3 BP 1059 EP 1070 DI 10.1021/ja00029a039 PG 12 WC Chemistry, Multidisciplinary SC Chemistry GA HB537 UT WOS:A1992HB53700039 ER PT J AU PARK, DJ MIN, HK RHEE, SG AF PARK, DJ MIN, HK RHEE, SG TI INHIBITION OF CD3-LINKED PHOSPHOLIPASE-C BY PHORBOL ESTER AND BY CAMP IS ASSOCIATED WITH DECREASED PHOSPHOTYROSINE AND INCREASED PHOSPHOSERINE CONTENTS OF PLC-GAMMA-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN KINASE-C; CELL ANTIGEN RECEPTOR; LYMPHOCYTE-T ACTIVATION; GROWTH-FACTOR; TYROSINE PHOSPHORYLATION; SIGNAL TRANSDUCTION; CALCIUM; COMPLEX; PATHWAY; TURNOVER AB The mechanisms by which phorbol 12-myristate 13-acetate (PMA) and cAMP attenuate the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdIns 4,5-P2) induced by ligation of the T-cell antigen receptor complex (TCR) was studied in the human Jurkat T-cell line. It has previously been shown that stimulation of Jurkat cells with antibodies to CD3, components of the TCR, elicits a rapid and transient phosphorylation of phospholipase C (PLC)-gamma-1, the predominant PLC isozyme in Jurkat cells, at multiple tyrosine residues and that such tyrosine phosphorylation leads to activation of PLC-gamma-1. Prior incubation of Jurkat cells with PMA or forskolin, which increases intracellular cAMP concentrations, prevented tyrosine phosphorylation of PLC-gamma-1 as well as the hydrolysis of PtdIns 4,5-P2 induced by ligation of CD3. Dose-response curves of PMA and of forskolin for the inhibition of PLC-gamma-1 tyrosine phosphorylation and of PtdIns 4,5-P2 hydrolysis were similar. These results suggest that the inhibition of PtdIns 4,5-P2 hydrolysis by PMA and cAMP is attributable to reduced tyrosine phosphorylation of PLC-gamma-1. Treatment of Jurkat cells with PMA or forskolin stimulated the phosphorylation of PLC-gamma-1 at serine 1248. PMA treatment also elicited the phosphorylation of PLC-gamma-1 at an unidentified serine site. Phosphopeptide map analysis indicated that the sites of PLC-gamma-1 phosphorylated in Jurkat cells treated with PMA and forskolin are the same as those phosphorylated in vitro by protein kinase C (PKC) and cAMP-dependent protein kinase (PKA), respectively. Stimulation of Jurkat cells with antibodies to CD3 also elicited phosphorylation of PLC-gamma-1 at serine 1248 and at the unidentified serine site phosphorylated in PLC-gamma-1 from PMA-treated cells. Thus, phosphorylation of PLC-gamma-1 by PKC or PKA at serine 1248 may modulate the interaction of PLC-gamma-1 with the protein tyrosine kinase or the protein tyrosine phosphatase; this altered interaction may, at least in part, be responsible for the decreased tyrosine phosphorylation of PLC-gamma-1 seen in PMA- and forskolin-treated Jurkat cells. Furthermore, in the absence of PMA, activation of PKC by diacylglycerol provides a negative feedback signal responsible for reducing the phosphotyrosine contents of PLC-gamma-1. C1 NHLBI,BIOCHEM LAB,BLDG 3,RM 122,BETHESDA,MD 20892. RI Park, Do-Joon/J-2736-2012 NR 43 TC 139 Z9 141 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 25 PY 1992 VL 267 IS 3 BP 1496 EP 1501 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HA485 UT WOS:A1992HA48500019 PM 1370476 ER PT J AU JOHNSON, AC KAGEYAMA, R POPESCU, NC PASTAN, I AF JOHNSON, AC KAGEYAMA, R POPESCU, NC PASTAN, I TI EXPRESSION AND CHROMOSOMAL LOCALIZATION OF THE GENE FOR THE HUMAN TRANSCRIPTIONAL REPRESSOR GCF SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FACTOR RECEPTOR GENE; REGION GENES; CHAIN LOCUS; TRANSLOCATION; PROMOTER; RNA; LYMPHOMA; INVITRO; ANTIGEN; CELLS AB GCF is a human transcriptional regulator that represses transcription of certain genes and is encoded by a 3-kilobase (kb) mRNA (Kageyama, R., and Pastan, I. (1989) Cell 59, 815-825). The expression of GCF was examined in a variety of clonal cell lines. The 3.0-kb GCF mRNA was found to be expressed at the highest level in HUT 102 cells (derived from a T-cell lymphoma). Elevated levels of the GCF mRNA were also noted in KATO III and AGS (gastric carcinomas), FEM-X (melanoma), and U266B1 (myeloma) cell lines. A human fibroblast cell line (WI38) did not express GCF mRNA, and no cross-hybridization to a mouse cell line (NIH 3T3) or monkey cell line (CV-1) could be detected. The GCF cDNA also hybridizes to RNA species of 4.5 and 1.2 kb. The 4.5-kb RNA has the same general expression pattern as the GCF mRNA. Hybridization of cellular RNA with various probes derived from the 3-kb cDNA revealed that the 4.5-kb RNA species only hybridizes to GCF cDNA probes from the extreme 5' end. By using single-stranded RNA probes, hybridization to the three RNA species was detected with the antisense probe for the 5' end (nucleotides 1-561). The single-stranded antisense probe for the region encompassing nucleotides 561-1692 hybridized to the 3.0- and 1.2-kb RNA species. The sense probes for these regions did not hybridize to these RNAs. The GCF gene was localized to a single locus, the chromosome 2 p11.1-11.2 region, by in situ hybridization. Treatment of human KB epidermoid carcinoma cells with phorbol 12-myristate 13-acetate (PMA) lead to a rapid induction of GCF RNA after 1 h and a decline to lower than control levels after 6 h. Epidermal growth factor receptor mRNAs were not increased by PMA until 2 h after treatment and were at their highest level only after GCF mRNAs were decreased. The 4.5- and 1.2-kb RNAs were also induced by PMA with the same kinetics as the GCF mRNA. These results show that the GCF gene is widely expressed in human tissues and cell lines and that the 4.5- and 1.2-kb RNAs have similar expression patterns. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NCI,DIV CANC ETIOL,BIOL LAB,BETHESDA,MD 20892. NR 43 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 JAN 25 PY 1992 VL 267 IS 3 BP 1689 EP 1694 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HA485 UT WOS:A1992HA48500046 PM 1370479 ER PT J AU WU, DQ LEE, CH RHEE, SG SIMON, MI AF WU, DQ LEE, CH RHEE, SG SIMON, MI TI ACTIVATION OF PHOSPHOLIPASE-C BY THE ALPHA-SUBUNITS OF THE GQ AND G11 PROTEINS IN TRANSFECTED COS-7 CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOTIDE-BINDING PROTEIN; ESCHERICHIA-COLI; PERTUSSIS TOXIN; GS-ALPHA; GTP; PURIFICATION; EXPRESSION; RECEPTOR; IDENTIFICATION; HYDROLYSIS AB High efficiency transient transfection was used to introduce cDNA corresponding to various G protein-alpha subunits into Cos-7 cells. The proteins that were subsequently synthesized were detected with specific G protein alpha-subunit antipeptide antiserum and were localized in the membrane fraction of the cell. Cells that were prelabeled with the [H-3]inositol and transfected with G-alpha(q), and G-alpha-11 cDNA showed marked increases in formation of [H-3]inositol phosphates after stimulation with aluminum fluoride. Co-transfection with cDNAs corresponding to phosphoinositide specific phospholipase C beta-1 (PI-PLC, beta-1) and to G-alpha(q) or G-alpha-11 resulted in even higher levels of inositol phosphate formation. The introduction of mutations that convert residue glutamine 209 to leucine in G-alpha(q) and G-alpha-11 resulted in persistent activation of PI-PLC and high steady state levels of inositol phosphates. On the other hand, transfection with a variety of other G-alpha subunit cDNAs, i.e. G-alpha(Z), G-alpha(OA), G-alpha(OB), transducin, and the glutamine 205 to leucine mutants of G-alpha(Z) and of G-alpha(OA) did not increase inositol phosphate formation. To further test the specificity of G protein activation of PI-PLC, a cell-free system was prepared by using washed membranes of transiently transfected cells and purified PI-PLC beta-1. Membranes derived from G-alpha(q) and G-alpha-11, but not G-alpha(OA) transfected cells, showed guanosine 5'-O-thiotriphosphate (GTP-gamma-S)-stimulated PIP2 hydrolysis. The activity seen in the system reconstituted with membranes derived from G-alpha-11-transfected cells was blocked by preincubation with specific G-alpha-11 antipeptide antibodies. All of these results are consistent with the conclusion that G-alpha(q) and G-alpha-11 cDNA encode proteins that in the presence of GTP-gamma-S specifically activate PI-PLC. C1 CALTECH, DIV BIOL, PASADENA, CA 91125 USA. NHLBI, BIOCHEM LAB, BETHESDA, MD 20892 USA. FU NIGMS NIH HHS [GM34236] NR 44 TC 303 Z9 303 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 25 PY 1992 VL 267 IS 3 BP 1811 EP 1817 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HA485 UT WOS:A1992HA48500064 PM 1309799 ER PT J AU FISHER, MT STADTMAN, ER AF FISHER, MT STADTMAN, ER TI OXIDATIVE MODIFICATION OF ESCHERICHIA-COLI GLUTAMINE-SYNTHETASE - DECREASES IN THE THERMODYNAMIC STABILITY OF PROTEIN-STRUCTURE AND SPECIFIC CHANGES IN THE ACTIVE-SITE CONFORMATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MIXED-FUNCTION OXIDATION; LIMITED PROTEOLYSIS; BINDING-SITE; DIVALENT CATIONS; OXYGEN RADICALS; DEGRADATION; INACTIVATION; TURNOVER; MODEL AB Metal catalyzed oxidation of specific amino acid residues has been proposed to be an important physiological mechanism of marking proteins for proteolytic degradation. After initial oxidative inactivation of dodecameric Escherichia coli glutamine synthetase (GS), the integrity of the GS active site and protein structure was assessed by monitoring ATP binding, observing a susceptibility of GS to tryptic cleavage, and comparative thermodynamic analysis. The tryptic cleavage rates of an active site linked central loop were significantly accelerated for the oxidized conformer. This tryptic cleavage was essentially prevented in the presence of glutamate for native GS but not for the oxidized conformer. The integrity of the ATP binding site in the oxidized GS was substantially altered as indicated by the reduction in fluorescence enhancement associated with ATP binding. Decreases in the free energies of quaternary protein structure and subunit interactions due to oxidative modification were determined by temperature and urea induced unfolding equilibrium measurements. Comparative thermal stability measurements of a partial unfolding transition indicated that the loss in stabilization free energy for the oxidized GS conformer was 1.3 kcal/mol dodecamer. Under alkaline conditions, the urea-induced disruption of quaternary and tertiary structures of oxidized and native GS were examined. This comparative analysis revealed that the free energies of the subunit interactions and unfolding of the dissociated monomers for oxidized GS were decreased by 1.5 and 1.7 kcal/mol, respectively. Our results suggest that small free energy decreases in GS protein structural stability of only 1-2 kcal/mol may be responsible for the selective proteolytic turnover of the oxidized GS. C1 NHLBI,BIOCHEM LAB,ENZYMES SECT,BLDG 3,RM 222,BETHESDA,MD 20892. NR 50 TC 44 Z9 45 U1 2 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 25 PY 1992 VL 267 IS 3 BP 1872 EP 1880 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HA485 UT WOS:A1992HA48500074 PM 1346137 ER PT J AU FALETTO, MB LINKO, P GOLDSTEIN, JA AF FALETTO, MB LINKO, P GOLDSTEIN, JA TI A SINGLE AMINO-ACID MUTATION (SER180-]CYS) DETERMINES THE POLYMORPHISM IN CYTOCHROME-P450G (P4502C13) BY ALTERING PROTEIN STABILITY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STEROID 21-HYDROXYLASE DEFICIENCY; YEAST SACCHAROMYCES-CEREVISIAE; RAT-LIVER; MESSENGER-RNA; LUNG-CANCER; EXPRESSION; DEBRISOQUINE; CDNA; P-450G; ISOZYMES AB Cytochrome P450g is polymorphic in the male rat. This polymorphism is characterized by a 20-40-fold difference in the hepatic content of P450g in the two phenotypes. Sequencing of cDNAs from high (+g) and low (-g) phenotype rats has shown that the low phenotype is due to a defective mRNA containing nine base mutations encoding 7 amino acid substitutions. To determine the role of these structural changes in the phenotypic expression of P450g, we altered each of these residues by site-directed mutagenesis in the present studies and expressed the normal and mutant cDNAs in Saccharomyces cerevisiae. P450+g protein was expressed at a level 4-6-fold higher than that of P450-g in yeast cells, despite the presence of identical mRNA levels. This difference in protein expression approaches the difference seen in the rat. A single amino acid change from Ser180 in P450+g to Cys in P450-g, in a highly conserved region in the P4502C subfamily, was found to be solely responsible for the phenotypic differences in expression of P450g. Protein half-life studies demonstrated that this mutation increases the degradation of P450g. This is the first example of a single amino acid substitution which alters the phenotypic expression of a P450 protein by affecting its stability. C1 NIEHS,BIOCHEM RISK ANAL LAB,RES TRIANGLE PK,NC 27709. RI Goldstein, Joyce/A-6681-2012 NR 54 TC 30 Z9 30 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 25 PY 1992 VL 267 IS 3 BP 2032 EP 2037 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HA485 UT WOS:A1992HA48500095 PM 1730734 ER PT J AU TARTAGLIA, LA GIMENO, CJ STORZ, G AMES, BN AF TARTAGLIA, LA GIMENO, CJ STORZ, G AMES, BN TI MULTIDEGENERATE DNA RECOGNITION BY THE OXYR TRANSCRIPTIONAL REGULATOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; ACTIVATOR PROTEINS; OXIDATIVE STRESS; INDUCIBLE GENES; PROMOTERS; SEQUENCE; BINDS; RESOLUTION; FAMILY AB The Escherichia coli OxyR protein, a regulator of hydrogen peroxide-inducible genes, is a potent stimulator of transcription in its oxidized form but not in its reduced form. OxyR protein purified in its oxidized form was found to bind four of its non-homologous, functional DNA-binding sites with over 10(6)-fold higher affinity than random DNA sequences. A similarly high DNA binding specificity was observed for the reduced (transcriptionally inactive) form of OxyR, consistent with a model in which the OxyR protein is bound to its recognition sequences even in the absence of an oxidative stress. Alignment of five functional OxyR-binding sites revealed a marked lack of perfectly conserved positions, yet an unusually high number of degenerate homologies (positions at which only two of the four possible base pairs are represented). Methylation interference assays on two OxyR-binding sites showed that OxyR contacts its recognition sequences predominantly at positions of degenerate homology. These results suggest that the OxyR protein specifically recognizes seemingly dissimilar sequences through the use of a multidegenerate recognition code. The chemical basis for a plausible degenerate recognition system is discussed. C1 UNIV CALIF BERKELEY,DIV BIOCHEM & MOLEC BIOL,BERKELEY,CA 94720. GENENTECH INC,SAN FRANCISCO,CA 94080. WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02141. NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. OI Storz, Gisela/0000-0001-6698-1241 FU NCI NIH HHS [CA39910]; NIEHS NIH HHS [ES01896]; NIGMS NIH HHS [GM19993] NR 21 TC 52 Z9 54 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 25 PY 1992 VL 267 IS 3 BP 2038 EP 2045 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HA485 UT WOS:A1992HA48500096 PM 1730735 ER PT J AU HAEFLIGER, JA BRUZZONE, R JENKINS, NA GILBERT, DJ COPELAND, NG PAUL, DL AF HAEFLIGER, JA BRUZZONE, R JENKINS, NA GILBERT, DJ COPELAND, NG PAUL, DL TI 4 NOVEL MEMBERS OF THE CONNEXIN FAMILY OF GAP JUNCTION PROTEINS - MOLECULAR-CLONING, EXPRESSION, AND CHROMOSOME MAPPING SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GENETIC-LINKAGE MAP; COMMUNICATION COMPARTMENTS; INTERSPECIFIC BACKCROSS; MOUSE EMBRYO; LIVER; LOCALIZATION; RAT; PERMEABILITY; CHANNELS; HEART AB We have used low stringency hybridization and polymerase chain reaction (PCR) amplification with degenerate oligonucleotides to identify four new members of the rat connexin gene family. On the basis of their predicted molecular mass, these proteins have been designated connexin (Cx) 40 (Cx40), Cx37, Cx33, and Cx31.1. The new connexins exhibit all of the conserved structural features of the connexin family, including highly similar extracellular and transmembrane domains but divergent major cytoplasmic domains. On the basis of primary sequence similarity, the connexin family may be divided into two classes. Cx40, Cx37, and Cx33 are similar to the previously characterized Cx43 and Cx46. Cx31.1 is similar to Cx26, Cx31, and Cx32. Cx37 and Cx40 mRNAs are expressed in a wide variety of adult organs and tissues, with particular abundance in lung. However, their relative levels are different in many organs and thus their distribution is not completely coincident. Cx33 and Cx31.1 genes exhibit a much more restricted pattern of expression; mRNAs are detected only in testes and skin, respectively. Chromosomal mapping studies indicate that Cx26 and Cx46 are tightly linked on chromosome 14, and Cx37 and Cx31.1 are linked on chromosome 4, while the rest of the connexin genes are dispersed. C1 HARVARD UNIV,SCH MED,DEPT ANAT & CELLULAR BIOL,BOSTON,MA 02115. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21072. RI Bruzzone, Roberto/C-4719-2009 OI Bruzzone, Roberto/0000-0003-4373-1447 FU NCI NIH HHS [N01-CO-74101]; NIGMS NIH HHS [GM37751] NR 61 TC 318 Z9 326 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 25 PY 1992 VL 267 IS 3 BP 2057 EP 2064 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HA485 UT WOS:A1992HA48500098 PM 1370487 ER PT J AU BRESNICK, EH BUSTIN, M MARSAUD, V RICHARDFOY, H HAGER, GL AF BRESNICK, EH BUSTIN, M MARSAUD, V RICHARDFOY, H HAGER, GL TI THE TRANSCRIPTIONALLY-ACTIVE MMTV PROMOTER IS DEPLETED OF HISTONE H1 SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MAMMARY-TUMOR VIRUS; LONG TERMINAL REPEAT; CELL-FREE SYSTEM; GLUCOCORTICOID REGULATION; HYPERSENSITIVE SITES; STEROID-HORMONES; RECEPTOR-BINDING; DNA-BINDING; CHROMATIN; GENES AB We have used an ultraviolet light cross-linking and immunoadsorption assay to demonstrate that histones H1 and H2B are bound to the repressed MMTV promoter. Hormone activation results in reduced H1 content with little or no change in H2B. High resolution analysis of the glucocorticoid-inducible DNasel hypersensitive region demonstrates an NF-1 footprint as well as specific sites of enhanced cleavage on nucleosome B and in the nucleosome B/nucleosome A linker. These results are consistent with a model in which binding of the glucocorticoid receptor to glucocorticoid regulatory elements on the surface of nucleosome B induces a chromatin transition that is necessary for transcription factor (NF-1 and TFIID) recruitment to the MMTV promoter. We hypothesize that association of histone H1 with important cis-elements on the promoter masks these sites, and glucocorticoid-induced displacement of H1 is necessary to expose factor binding sites at the 3' edge of nucleosome B, in the nucleosome B/nucleosome A linker and at the 5' edge of nucleosome A. C1 NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. HOP KREMLIN BICETRE,UNITE RECH COMMUN HORMONALES,INSERM,U-33,F-94276 LE KREMLIN BICETR,FRANCE. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RI Bustin, Michael/G-6155-2015 NR 49 TC 193 Z9 194 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 25 PY 1992 VL 20 IS 2 BP 273 EP 278 DI 10.1093/nar/20.2.273 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HC136 UT WOS:A1992HC13600016 PM 1311071 ER PT J AU BURDETT, LA QI, SM CHEN, ZQ LAUTENBERGER, JA PAPAS, TS AF BURDETT, LA QI, SM CHEN, ZQ LAUTENBERGER, JA PAPAS, TS TI CHARACTERIZATION OF THE CDNA SEQUENCES OF 2 XENOPUS-ETS-2 PROTOONCOGENES SO NUCLEIC ACIDS RESEARCH LA English DT Note ID PROTEINS C1 NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702. NR 6 TC 5 Z9 7 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 25 PY 1992 VL 20 IS 2 BP 371 EP 371 DI 10.1093/nar/20.2.371 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HC136 UT WOS:A1992HC13600035 PM 1741266 ER PT J AU MORRISON, A SUGINO, A AF MORRISON, A SUGINO, A TI NUCLEOTIDE-SEQUENCE OF THE POL3 GENE ENCODING DNA POLYMERASE-III (DELTA) OF SACCHAROMYCES-CEREVISIAE SO NUCLEIC ACIDS RESEARCH LA English DT Note RP MORRISON, A (reprint author), NIEHS,MOLEC GENET LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 4 TC 12 Z9 13 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN 25 PY 1992 VL 20 IS 2 BP 375 EP 375 DI 10.1093/nar/20.2.375 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HC136 UT WOS:A1992HC13600039 PM 1741270 ER PT J AU WARBURG, A MILLER, LH AF WARBURG, A MILLER, LH TI SPOROGONIC DEVELOPMENT OF A MALARIA PARASITE INVITRO SO SCIENCE LA English DT Article ID EXTRACELLULAR-MATRIX; PLASMODIUM; MOSQUITO; CULTURE AB The sporogonic cycle of the avian malaria parasite Plasmodium gallinaceum was completed in vitro. Ookinetes (motile zygotes) were seeded onto a murine basement membrane-like gel (Matrigel) in coculture with Drosophila melanogaster cells (Schneider's L2). Transformation into oocysts as well as subsequent growth and differentiation were observed in parasites attached to Matrigel and depended on the presence of L2 cells. Sporozoites were first observed on day 10 in culture. Specific circumsporozoite protein antigenicity was identified in mature oocysts and in sporozoites. It is now possible to follow the entire life cycle of Plasmodium in vitro. RP WARBURG, A (reprint author), NIAID,PARASIT DIS LAB,MALARIA SECT,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 21 TC 53 Z9 54 U1 0 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JAN 24 PY 1992 VL 255 IS 5043 BP 448 EP 450 DI 10.1126/science.1734521 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HA590 UT WOS:A1992HA59000035 PM 1734521 ER PT J AU HU, SL ABRAMS, K BARBER, GN MORAN, P ZARLING, JM LANGLOIS, AJ KULLER, L MORTON, WR BENVENISTE, RE AF HU, SL ABRAMS, K BARBER, GN MORAN, P ZARLING, JM LANGLOIS, AJ KULLER, L MORTON, WR BENVENISTE, RE TI PROTECTION OF MACAQUES AGAINST SIV INFECTION BY SUBUNIT VACCINES OF SIV ENVELOPE GLYCOPROTEIN GP160 SO SCIENCE LA English DT Article ID IMMUNODEFICIENCY VIRUS-INFECTION; EXPRESSION; LENTIVIRUS AB Simian immunodeficiency virus (SIV) is a primate lentivirus related to human immunodeficiency viruses and is an etiologic agent for acquired immunodeficiency syndrome (AIDS)-like diseases in macaques. To date, only inactivated whole virus vaccines have been shown to protect macaques against SIV infection. Protective immunity was elicited by recombinant subunit vaccines. Four Macaca fascicularis were immunized with recombinant vaccinia virus expressing SIVmne gpl60 and were boosted with gpl60 produced in baculovirus-infected cells. All four animals were protected against an intravenous challenge of the homologous virus at one to nine animal-infectious doses. These results indicate that immunization with viral envelope antigens alone is sufficient to elicit protective immunity against a primate immunodeficiency virus. The combination immunization regimen, similar to one now being evaluated in humans as candidate human immunodeficiency virus (HIV)-1 vaccines, appears to be an effective way to elicit such immune responses. C1 UNIV WASHINGTON,SEATTLE,WA 98195. DUKE UNIV,MED CTR,DURHAM,NC 27710. NCI,FREDERICK,MD 21701. RP HU, SL (reprint author), BRISTOL MYERS SQUIBB PHARMACEUT RES INST,SEATTLE,WA 98121, USA. RI Hu, Shiu-Lok/A-3196-2008 OI Hu, Shiu-Lok/0000-0003-4336-7964 FU NCRR NIH HHS [RR00166]; NIAID NIH HHS [AI26503, R01 AI28065] NR 32 TC 310 Z9 316 U1 0 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JAN 24 PY 1992 VL 255 IS 5043 BP 456 EP 459 DI 10.1126/science.1531159 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HA590 UT WOS:A1992HA59000038 PM 1531159 ER PT J AU CHIN, KV UEDA, K PASTAN, I GOTTESMAN, MM AF CHIN, KV UEDA, K PASTAN, I GOTTESMAN, MM TI MODULATION OF ACTIVITY OF THE PROMOTER OF THE HUMAN MDR1 GENE BY RAS AND P53 SO SCIENCE LA English DT Article ID MULTIDRUG-RESISTANCE GENE; P-GLYCOPROTEIN; HUMAN-TUMORS; CELLS; EXPRESSION; TISSUES; PROTEIN; LIVER; DNA; TRANSFORMATION AB Drug resistance in human cancer is associated with overexpression of the multidrug resistance (MDR1) gene, which confers cross-resistance to hydrophobic natural product cytotoxic drugs. Expression of the MDR1 gene can occur de novo in human cancers in the absence of drug treatment. The promoter of the human MDR1 gene was shown to be a target for the c-Ha-Ras-1 oncogene and the p53 tumor suppressor gene products, both of which are associated with tumor progression. The stimulatory effect of c-Ha-Ras-1 was not specific for the MDR1 promoter alone, whereas a mutant p53 specifically stimulated the MDR1 promoter and wild-type p53 exerted specific repression. These results imply that the MDR1 gene could be activated during tumor progression associated with mutations in Ras and p53. C1 NCI,CELL BIOL LAB,BLDG 37,ROOM 1B22,BETHESDA,MD 20892. KYOTO UNIV,DEPT AGR CHEM,KYOTO 606,JAPAN. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. RI Chin, Khew-Voon/F-2670-2013; Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 43 TC 753 Z9 783 U1 2 U2 7 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JAN 24 PY 1992 VL 255 IS 5043 BP 459 EP 462 DI 10.1126/science.1346476 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HA590 UT WOS:A1992HA59000039 PM 1346476 ER PT J AU NAKAJIMA, T WANG, RS ELOVAARA, E PARK, SS GELBOIN, HV VAINIO, H AF NAKAJIMA, T WANG, RS ELOVAARA, E PARK, SS GELBOIN, HV VAINIO, H TI A COMPARATIVE-STUDY ON THE CONTRIBUTION OF CYTOCHROME-P450 ISOZYMES TO METABOLISM OF BENZENE, TOLUENE AND TRICHLOROETHYLENE IN RAT-LIVER SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; INDUCIBLE CYTOCHROME-P-450; HEPATIC CYTOCHROME-P-450; STEROID-METABOLISM; MICROSOMES; ETHANOL; FORMS; EXPRESSION AB The contribution of P450IIE1, P450IIC11/6, P450IIB1/2 and P450IA1/2 to the formation of chloral hydrate (CH) from trichloroethylene (TRI) was investigated in microsomes from control, ethanol-, phenobarbital (PB)- and 3-methylcholanthrene (MC)-treated rats using monoclonal antibodies (MAbs) to the respective P450 isozymes, and compared with their roles in benzene and toluene metabolism. Anti-P450IIE1 inhibited the formation of CH from TRI more strongly in microsomes from ethanol-treated rats than in microsomes from control rats at low concentration of TRI when net inhibition was compared. Anti-P450IIC11/6 inhibited CH formation in microsomes from control and PB-treated rats at high, not low, concentration of TRI, but the net inhibition in control microsomes was less than that due to anti-P450IIE1. Anti-P450IIB1/2 and anti-P450IA1/2 also inhibited CH formation from TRI in microsomes from PB- and MC-treated rats, respectively, stronger at high substrate concentration than at low concentration. These results indicate that P450IIE1, P450IIC11/6, P450IIB1/2 and P450IA1/2 are involved in the metabolic step from TRI to CH, and the first isozyme may be a low-K(m) TRI oxidase and the others high-K(m) one. Comparing the contributions of four isozymes to benzene, toluene and TRI metabolism, all four acted in the metabolism of these compounds, but P450IIE1 did not catalyse omicron-cresol formation nor P450IA1/2 benzyl alcohol formation from toluene, suggesting regioselectivity to toluene metabolism in the action of these two isozymes. The contribution of P450IIE1 in benzene and TRI oxidation was greater than that of P450IIC11/6, but the reverse was seen with respect to benzyl alcohol formation from toluene, indicating that P450IIC11/6 is relatively inactive towards benzene and TRI oxidation, but is primarily involved in toluene metabolism. P450IIB1/2 and P450IIC11/6 attacked all the metabolic positions studied, but only in the side-chain metabolism of toluene was their contribution significant, suggesting that these two isozymes are quite similar in function. C1 INST OCCUPAT HLTH,DEPT IND HYG & TOXICOL,SF-00250 HELSINKI,FINLAND. INT AGCY RES CANC,F-69372 LYONS,FRANCE. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RP NAKAJIMA, T (reprint author), SHINSHU UNIV,SCH MED,DEPT HYG,MATSUMOTO,NAGANO 390,JAPAN. NR 31 TC 104 Z9 105 U1 0 U2 3 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 JAN 22 PY 1992 VL 43 IS 2 BP 251 EP 257 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HB891 UT WOS:A1992HB89100018 PM 1739413 ER PT J AU WEHR, TA AF WEHR, TA TI IMPROVEMENT OF DEPRESSION AND TRIGGERING OF MANIA BY SLEEP-DEPRIVATION SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ANTIDEPRESSANT RESPONSE; PHASE ADVANCE; WAKE CYCLE; POTENTIATION; PREDICTION; SECRETION; STATES; TSH RP WEHR, TA (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,BLDG 10,ROOM 4S-239,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 28 TC 36 Z9 37 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 22 PY 1992 VL 267 IS 4 BP 548 EP 551 DI 10.1001/jama.267.4.548 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA GZ439 UT WOS:A1992GZ43900033 PM 1729578 ER PT J AU BAGDY, G SVED, AF MURPHY, DL SZEMEREDI, K AF BAGDY, G SVED, AF MURPHY, DL SZEMEREDI, K TI PHARMACOLOGICAL CHARACTERIZATION OF SEROTONIN RECEPTOR SUBTYPES INVOLVED IN VASOPRESSIN AND PLASMA-RENIN ACTIVITY RESPONSES TO SEROTONIN AGONISTS SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE 5-HT RECEPTOR AGONISTS; 5-HT RECEPTOR ANTAGONISTS; BLOOD PRESSURE; PLASMA RENIN ACTIVITY; VASOPRESSIN; M-CPP (1-3-CHLOROPHENYL)PIPERAZINE); DOI (1-(2,5-DIMETHOXY-4-IODOPHENYL)-2-AMINOPROPANE); 8-OH-DPAT (8-HYDROXY-2-(DI-N-PROPYLAMINO)TETRALIN) ID TRACTUS SOLITARIUS LESIONS; CONSCIOUS RATS; M-CHLOROPHENYLPIPERAZINE; 5-HT1C RECEPTORS; BLOOD-PRESSURE; HEART-RATE; ACTIVATION; SECRETION; RELEASE; SYSTEM AB Serotonergic drugs with 5-HT2 receptor agonist properties have been suggested to increase plasma vasopressin concentration, blood pressure (BP) and plasma renin activity (PRA). To study whether these actions are mediated by the same or different receptors, we used three potent 5-HT agonists with different structures and receptor binding profiles. All drugs were administered i.v. to conscious, unrestrained rats. The selective agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), which has high affinity for 5-HT2 receptors, caused marked increases in BP and PRA but no change in plasma vasopressin concentrations. The 5-HT1C agonist, m-chlorophenylpiperazine (m-CPP), which also binds to other 5-HT receptors, caused moderate increases in BP and PRA and significantly elevated plasma vasopressin concentrations. The 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), did not increase any of these parameters. BP and PRA elevations paralleled each other after all drugs, while vasopressin responses were clearly different. Vasopressin responses to m-CPP were entirely antagonised by the 5-HT1/5-HT2 antagonist metergoline, partially by the 5-HT2/5-HT1C antagonists ritanserin and LY 53857, but not by the 5-HT2 antagonist ketanserin. Ritanserin, LY53857 and ketanserin all very effectively blocked BP responses to m-CPP. These findings suggest that BP and PRA but not vasopressin responses are mediated by 5-HT2 receptors. Vasopressin secretion is mediated by 5-HT1 receptors, most likely by 5-HT1C receptors. C1 UNIV PITTSBURGH,DEPT BEHAV SCI,PITTSBURGH,PA 15260. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NINCDS,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. RP BAGDY, G (reprint author), NATL INST NERVOUS & MENTAL DIS 2,EXPTL MED LAB,HUVOSVOLGYI UT 116,POB 1,H-1281 BUDAPEST 27,HUNGARY. OI Bagdy, Gyorgy/0000-0001-8141-3410 NR 20 TC 55 Z9 54 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 JAN 21 PY 1992 VL 210 IS 3 BP 285 EP 289 DI 10.1016/0014-2999(92)90417-3 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HC017 UT WOS:A1992HC01700010 PM 1535317 ER PT J AU GLOWA, JR PANLILIO, LV BRENNEMAN, DE GOZES, I FRIDKIN, M HILL, JM AF GLOWA, JR PANLILIO, LV BRENNEMAN, DE GOZES, I FRIDKIN, M HILL, JM TI LEARNING IMPAIRMENT FOLLOWING INTRACEREBRAL ADMINISTRATION OF THE HIV ENVELOPE PROTEIN GP120 OR A VIP ANTAGONIST SO BRAIN RESEARCH LA English DT Article DE HUMAN IMMUNODEFICIENCY VIRUS; EXTERNAL ENVELOPE GLYCOPROTEIN; AUTOIMMUNE DEFICIENCY SYNDROME; DEMENTIA; VASOACTIVE INTESTINAL PEPTIDE; MEMORY ID HUMAN IMMUNODEFICIENCY VIRUS; VASOACTIVE-INTESTINAL-PEPTIDE; LONG-TERM POTENTIATION; RECEPTOR-BINDING; INFECTION; AIDS; BRAINS; CD4; GLYCOPROTEIN; PREVENTION AB The external envelope glycoprotein (gp120) of the human immunodeficiency virus (HIV) has been shown to be toxic to neurons in culture. To further investigate the neurological effects of gp120, the involvement of this protein with the acquisition of spatial discrimination was assessed. Both native and recombinant gp120 were administered into the cerebral ventricles of adult rats and performance was evaluated in the Morris swim maze. Gp120 treatment retarded acquisition after daily administration of 12 ng. The specificity of this impairment was demonstrated in that the performance of animals given the same amount of gp160 from recombinant baculovirus was not different from animals given saline. Vasoactive intestinal peptide (VIP) has been shown to block gp120-induced neurotoxicity in culture and a VIP receptor antagonist has displayed toxic properties to neurons in culture. We show here that this antagonist, which competitively inhibits VIP binding and blocks VIP-mediated functions in cell cultures from the CNS, also produced an impairment of performance. This retardation was attenuated by cotreatment with VIP, supporting the specificity of the observed impairment. Thus, gp120 and the VIP antagonist produced similar retardation of spatial discrimination, suggesting that both may impair memory for spatially related stimulus control. C1 NICHHD,DEV NEUROBIOL LAB,NEUROCHEM UNIT,BETHESDA,MD 20892. TEL AVIV UNIV,SACKLER SCH MED,DEPT CHEM PATHOL,TEL AVIV,ISRAEL. WEIZMANN INST SCI,DEPT ORGAN CHEM,IL-76100 REHOVOT,ISRAEL. AMERICAN UNIV,DEPT PSYCHOL,WASHINGTON,DC. RP GLOWA, JR (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,BIOPSYCHOL UNIT,BLDG 14D,RM 311,BETHESDA,MD 20892, USA. NR 40 TC 136 Z9 138 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 20 PY 1992 VL 570 IS 1-2 BP 49 EP 53 DI 10.1016/0006-8993(92)90562-N PG 5 WC Neurosciences SC Neurosciences & Neurology GA HB005 UT WOS:A1992HB00500007 PM 1617429 ER PT J AU STERNBERG, EM GLOWA, JR SMITH, MA CALOGERO, AE LISTWAK, SJ AKSENTIJEVICH, S CHROUSOS, GP WILDER, RL GOLD, PW AF STERNBERG, EM GLOWA, JR SMITH, MA CALOGERO, AE LISTWAK, SJ AKSENTIJEVICH, S CHROUSOS, GP WILDER, RL GOLD, PW TI CORTICOTROPIN RELEASING HORMONE RELATED BEHAVIORAL AND NEUROENDOCRINE RESPONSES TO STRESS IN LEWIS AND FISCHER RATS SO BRAIN RESEARCH LA English DT Article DE CORTICOTROPIN RELEASING HORMONE; STRESS; NEUROENDOCRINE RESPONSE; STREPTOCOCCAL CELL WALL-INDUCED ARTHRITIS; MESSENGER RIBONUCLEIC ACID ID PITUITARY-ADRENAL AXIS; WALL-INDUCED ARTHRITIS; BIOCHEMICAL MANIFESTATIONS; ADRENOCORTICAL RESPONSES; NERVOUS-SYSTEM; ANIMAL-MODEL; INTERLEUKIN-1; DEPRESSION; SECRETION; NEUROBIOLOGY AB We have recently shown that susceptibility to streptococcal cell wall (SCW)-induced arthritis in Lewis (LEW/N) rats is related to a lack of glucocorticoid restraint of inflammation while the relative SCW arthritis resistance in histocompatible Fischer (F344/N) rats is related to their greater hypothalamic-pituitary-adrenal (HPA) axis response. The difference in pituitary-adrenal responsiveness results from decreased inflammatory mediator-induced hypothalamic corticotropin-releasing hormone (CRH) biosynthesis and secretion in LEW/N rats. Because CRH not only activates the pituitary-adrenal axis, but also is associated with behavioral responses that are adaptive during stressful situations, we wished to determine if the differential LEW/N and F344/N CRH responsiveness to inflammatory mediators could also be associated with differences in neuroendocrine and behavioral responses to physical and emotional stressors. In this study, LEW/N rats exhibited significant differences compared to F344/N rats, in plasma adrenocorticotropin hormone (ACTH) and corticosterone responses during exposure to an open field, swim stress, restraint or ether. Furthermore, hypothalamic paraventricular CRH mRNA expression was also significantly lower in LEW/N compared to F344/N rats after restraint. These differences in neuroendocrine responses were associated with differences in behavioral responses in LEW/N compared to F344/N rats in the open field. Outbred HSD rats, which have intermediate and overlapping arthritis susceptibility compared to LEW/N and F344/N rats, exhibited intermediate and overlapping plasma corticosterone and behavioral responses to stressful stimuli compared to the two inbred strains. These data suggest that the differences in CRH responses in these strains may contribute to the behavioral and neuroendocrine differences we have observed. Therefore these strains may provide a useful animal model for studying the relationship between behavior, neuroendocrine and inflammatory responses. C1 NIAMS, ARTHRITIS & RHEUMATISM BRANCH, BETHESDA, MD 20892 USA. NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. RP NIMH, ALCOHOL DRUG ABUSE & MENTAL HLTH ADM, CLIN NEUROENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NR 39 TC 229 Z9 230 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD JAN 20 PY 1992 VL 570 IS 1-2 BP 54 EP 60 DI 10.1016/0006-8993(92)90563-O PG 7 WC Neurosciences SC Neurosciences & Neurology GA HB005 UT WOS:A1992HB00500008 PM 1319794 ER PT J AU AGUAYO, LG WHITE, G AF AGUAYO, LG WHITE, G TI EFFECTS OF NERVE GROWTH-FACTOR ON TTX-SENSITIVITY AND CAPSAICIN-SENSITIVITY IN ADULT-RAT SENSORY NEURONS SO BRAIN RESEARCH LA English DT Article DE NA+ CURRENT; TETRODOTOXIN; CAPSAICIN; DORSAL ROOT GANGLION; TROPHIC FACTOR; NERVE GROWTH FACTOR; PATCH CLAMP ID ROOT GANGLION NEURONS; SODIUM CURRENTS; IONIC CURRENTS; GUINEA-PIG; CELLS; MEMBRANE; COMPONENTS; RESPONSES; SURVIVAL; AXOTOMY AB We have investigated the effects of nerve growth factor (NGF, 2.5 ng/ml for 1-2 weeks) on enriched adult rat dorsal root ganglion (DRG) neurons maintained in cell culture in defined media. Whole-cell recordings in cells cultured in the absence and presence of NGF revealed no significant difference in resting membrane potential and input resistance. However, the threshold for spike generation was significantly lower in untreated cells than in treated cells; -25 +/- 1.1 mV vs -19 +/- 2.2 mV, respectively. The sensitivity of the Na+ spike to tetrodotoxin (TTX, 1-mu-M) was different in cells cultured in the absence or presence of NGF. For example, spikes were abolished by TTX in 100% of untreated cells, while in NGF-treated cells the spike was abolished in only 41% of the neurons. Chemosensitivity of DRG neurons was also different in the absence and presence of NGF. For example, the percent of neurons in which a current activated by 8-methyl-N-vanillyl-6-nonenamide (capsaicin, 500 nM) was detected, increased from 18% in untreated cells to 55% in NGF-treated cells. NGF did not influence the number of cells surviving. The results indicate that NGF can regulate TTX and capsaicin sensitivity in these adult rat sensory neurons. Our experimental protocol indicates that this effect is not mediated by a factor in the serum or released from non-neuronal cells. C1 NIAAA,PHYSIOL & PHARMACOL STUDIES,ELECTROPHYSIOL SECT,ROCKVILLE,MD 20852. NR 35 TC 71 Z9 71 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 20 PY 1992 VL 570 IS 1-2 BP 61 EP 67 DI 10.1016/0006-8993(92)90564-P PG 7 WC Neurosciences SC Neurosciences & Neurology GA HB005 UT WOS:A1992HB00500009 PM 1617430 ER PT J AU ZORAD, S TSUTSUMI, K SAAVEDRA, JM AF ZORAD, S TSUTSUMI, K SAAVEDRA, JM TI SELECTIVE LOCALIZATION OF C-ATRIAL NATRIURETIC PEPTIDE RECEPTORS IN THE RAT-BRAIN SO BRAIN RESEARCH LA English DT Article DE ATRIOPEPTIN; CLEARANCE RECEPTOR; CHOROID PLEXUS; MENINGES; OLFACTORY BULB ID HYPERTENSIVE RATS; CHOROID-PLEXUS; BINDING-SITES; CYCLIC-GMP; AUTORADIOGRAPHY; FAMILY AB We studied the distribution of C atrial natriuretic peptide (C-ANP) receptors in the rat brain after incubation with I-125-rANP, and competition with the selective C-ANP receptor competitor C-ANP(4-23) (10(-6) M). C-ANP receptors were selectively localized to a few structures, the external plexiform layer of the olfactory bulb, the arachnoid mater and the choroid plexus, and their amount corresponds to 25%, 75% and 35%, respectively, of the ANP specific binding. These data suggest specialized functions for C-ANP receptors in brain. C1 NIMH,CLIN SCI LAB,PHARMACOL SECT,9000 ROCKVILLE PIKE,BLDG 10,RM 2D-45,BETHESDA,MD 20892. NR 21 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 20 PY 1992 VL 570 IS 1-2 BP 149 EP 153 DI 10.1016/0006-8993(92)90575-T PG 5 WC Neurosciences SC Neurosciences & Neurology GA HB005 UT WOS:A1992HB00500020 PM 1319791 ER PT J AU HEYES, MP JORDAN, EK LEE, K SAITO, K FRANK, JA SNOY, PJ MARKEY, SP GRAVELL, M AF HEYES, MP JORDAN, EK LEE, K SAITO, K FRANK, JA SNOY, PJ MARKEY, SP GRAVELL, M TI RELATIONSHIP OF NEUROLOGIC STATUS IN MACAQUES INFECTED WITH THE SIMIAN IMMUNODEFICIENCY VIRUS TO CEREBROSPINAL-FLUID QUINOLINIC ACID AND KYNURENIC ACID SO BRAIN RESEARCH LA English DT Article DE EXCITOTOXIN; N-METHYL-D-ASPARTATE RECEPTOR; BRAIN ATROPHY; SIMIAN IMMUNODEFICIENCY VIRUS; KYNURENINE PATHWAY; INDOLEAMINE-2,3-DIOXYGENASE ID METHYL-D-ASPARTATE; CENTRAL NERVOUS-SYSTEM; AIDS DEMENTIA COMPLEX; INDOLEAMINE 2,3-DIOXYGENASE; TRYPTOPHAN DEGRADATION; HUNTINGTONS-DISEASE; RHESUS MACAQUES; HIV-1 INFECTION; D-RETROVIRUS; RAT-BRAIN AB Increased concentrations of the excitotoxin quinolinic acid (QUIN) have been implicated in the neurologic deficits and brain atrophy that may accompany infection with the human immunodeficiency virus type-1. Key neuropathologic features of the AIDS encephalitis are replicated in some macaques following infection with the simian immunodeficiency virus (SIV). In the present studies, cerebrospinal fluid (CSF) QUIN concentrations increased within 2 weeks following infection of 11 rhesus macaques (Macaca mulatta) with a neurotropic sooty mangabey isolate of the simian immunodeficiency virus (SIV(sm)) and were sustained to > 2 standard deviations above uninfected control macaques. Highest CSF QUIN concentrations (up to 400-fold above pre-inoculation levels) were observed in 6 SIV(sm)-infected macaques with motor and behavioral abnormalities during life, brain atrophy on MRI scan and inflammatory lesions within the brain and meninges. Four of the 6 neurologic macaques deteriorated rapidly within 12 weeks after inoculation and had substantially larger increases in CSF QUIN levels than 2 other neurologic macaques and 5 macaques without neurologic signs which survived for longer than 37 weeks. Increases in serum QUIN and CSF kynurenic acid also occurred but generally to a lesser degree than the increases in CSF QUIN. In some animals, increases in serum L-kynurenine concentrations and reductions in CSF and serum L-tryptophan occurred and were consistent with activation of indoleamine-2, 3-dioxygenase, the first enzyme of the kynurenine pathway in extrahepatic tissues. CSF QUIN exceeded serum QUIN in 8.8% of samples from macaques with neurologic signs, supporting increased QUIN synthesis within the central nervous system. Production of [C-13(6)]QUIN was demonstrated in one SIV(sm)-infected macaque and one unifected control macaque following an intracisternal injection of [C-13(6)]L-tryptophan and suggests that L-tryptophan is a substrate for QUIN synthesis within the nervous system or meninges, althouth the cellular localization of QUIN synthesis remain to be determined. We conclude that increases in kynurenine pathway metabolism occur in SIV-infected macaques and are most prominent in macaques with neurologic signs. Macaques infected with SIV offer a model to investigate the relationship between the metabolism of neuroactive kynurenines and neurologic disturbances associated with retroviral infection. C1 NIH, CLIN CTR DIAGNOST RADIOL, BETHESDA, MD 20892 USA. US FDA, BETHESDA, MD 20892 USA. NINCDS, CENT NERVOUS SYST STUDIES LAB, BETHESDA, MD 20892 USA. RP HEYES, MP (reprint author), NIMH, CLIN SCI LAB, ANALYT BIOCHEM SECT, BLDG 10, ROOM 3D40, BETHESDA, MD 20892 USA. NR 65 TC 88 Z9 89 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 20 PY 1992 VL 570 IS 1-2 BP 237 EP 250 DI 10.1016/0006-8993(92)90587-Y PG 14 WC Neurosciences SC Neurosciences & Neurology GA HB005 UT WOS:A1992HB00500032 PM 1535532 ER PT J AU STETLERSTEVENSON, WG BERSCH, N GOLDE, DW AF STETLERSTEVENSON, WG BERSCH, N GOLDE, DW TI TISSUE INHIBITOR OF METALLOPROTEINASE-2 (TIMP-2) HAS ERYTHROID-POTENTIATING ACTIVITY SO FEBS LETTERS LA English DT Article DE METALLOPROTEINASE INHIBITOR; COLLAGENASE INHIBITOR; ERYTHROPOIESIS; CFU-E; BFU-E ID BURST-PROMOTING ACTIVITY; HUMAN GM-CSF; CELL-LINE; COLLAGENASE INHIBITOR; ERYTHROPOIESIS INVITRO; PROGENITOR CELLS; GROWTH-HORMONE; PURIFICATION; EXPRESSION; PROLIFERATION AB Tissue inhibitor of metalloproteinase (TIMP) was purified and molecularly cloned on the basis of its erythroid-potentiating activity (EPA). TIMP/EPA appears to be a bifunctional molecule with both growth factor and anti-enzymatic activity. Recently, a second TIMP-related molecule was identified and we have investigated its possible erythroid-potentiating activity. Native, purified human TIMP-2 was assayed for erythroid-potentiating activity using an in vitro erythroid burst formation assay and was compared with that of previously characterized recombinant EPA/TIMP-1. The results demonstrate that both members of the tissue inhibitor of metalloproteinase family, TIMP-1 and TIMP-2, possessed erythroid potentiating activity which was inhibited by antibodies developed to neutralize EPA. These results suggest that TIMP-2 shares a common structural domain with EPA/TIMP-1 that is responsible for the erythroid-potentiating activity of these inhibitors. Therefore, TIMP-1 and TIMP-2, with both anti-protease activity and growth factor activity, join a family of bifunctional molecules such as fibroblast growth factor and thrombin which have both enzymatic and growth factor activity. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,DIV HEMATOL ONCOL,LOS ANGELES,CA 90024. RP STETLERSTEVENSON, WG (reprint author), NCI,PATHOL LAB,BLDG 10A,2A33,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 FU NCI NIH HHS [CA30388, CA32737]; NHLBI NIH HHS [HL42701] NR 40 TC 158 Z9 159 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JAN 20 PY 1992 VL 296 IS 2 BP 231 EP 234 DI 10.1016/0014-5793(92)80386-U PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA HA637 UT WOS:A1992HA63700026 PM 1370805 ER PT J AU WEISS, GH BENDLER, JT SHLESINGER, MF AF WEISS, GH BENDLER, JT SHLESINGER, MF TI CONTINUOUS-SITE MODEL FOR LANGMUIR GAS SORPTION IN GLASSY-POLYMERS SO MACROMOLECULES LA English DT Note ID POLYCARBONATE C1 GE,CORP RES & DEV,BIOL SCI LAB,SCHENECTADY,NY 12301. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. USN,OFF RES,DIV PHYS,ARLINGTON,VA 22217. NR 18 TC 29 Z9 29 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0024-9297 J9 MACROMOLECULES JI Macromolecules PD JAN 20 PY 1992 VL 25 IS 2 BP 990 EP 992 DI 10.1021/ma00028a074 PG 3 WC Polymer Science SC Polymer Science GA HB418 UT WOS:A1992HB41800074 ER PT J AU BIECHE, I CHAMPEME, MH MATIFAS, F HACENE, K CALLAHAN, R LIDEREAU, R AF BIECHE, I CHAMPEME, MH MATIFAS, F HACENE, K CALLAHAN, R LIDEREAU, R TI LOSS OF HETEROZYGOSITY ON CHROMOSOME-7Q AND AGGRESSIVE PRIMARY BREAST-CANCER SO LANCET LA English DT Article ID SHORT ARM; CELL CARCINOMA; ALLELE LOSS; GENES; DELETIONS; LUNG; 11P; ADENOCARCINOMA; METASTASIS; ONCOGENE AB Genetic alterations are believed to be important in the origin and dissemination of breast cancer. Cytogenetic rearrangements on chromosome 7 are common in breast tumours. We used the c-met proto-oncogene probe, which detects sequences on chromosome 7q31, to analyse tumour and blood leucocyte DNA samples from 245 patients with primary breast cancers. The pmetH polymorphic probe detected a high frequency of allele loss (40.5%) among the 121 informative (heterozygous) patients. This genetic alteration was not significantly associated with standard prognostic features including tumour size, histopathological grade, and lymph-node or steroid receptor status. However, patients with loss of heterozygosity on chromosome 7q31 in primary tumour DNA had significantly shorter metastasis-free survival (p = 0.00022) and overall survival (p = 0.0036) after surgery than patients without this alteration. These findings indicate that this region of chromosome 7 might be the site of a breast tumour or metastasis suppressor gene. C1 CTR RENE HUGUENIN,ONCOVIROL LAB,5 RUE GASTON LATOUCHE,F-92211 ST CLOUD,FRANCE. CTR RENE HUGUENIN,DEPT MED STAT,F-92211 ST CLOUD,FRANCE. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NR 40 TC 181 Z9 181 U1 0 U2 2 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JAN 18 PY 1992 VL 339 IS 8786 BP 139 EP 143 DI 10.1016/0140-6736(92)90208-K PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA GZ968 UT WOS:A1992GZ96800002 PM 1346009 ER PT J AU MCDIARMID, R AF MCDIARMID, R TI AN EXPERIMENTAL ESTIMATE OF RYDBERG VALENCE MIXING IN CONJUGATED DIENES SO CHEMICAL PHYSICS LETTERS LA English DT Article ID CONFIGURATION-INTERACTION CALCULATIONS; TRANS-BUTADIENE; ELECTRONIC-SPECTRUM; STATES; TRANS-1,3-BUTADIENE; 1,3-BUTADIENE; IMPACT; BOND AB The displacements of the B2 3p Rydberg state of cyclopentadiene and the assumed B(u) 3p Rydberg state of butadiene from their "unperturbed" values have been experimentally determined. These experimental energies and energy differences have been used to estimate the extent of B(u) (B2) Rydberg state-valence state mixing in butadiene and cyclopentadiene. Far more extensive mixing was found in butadiene than in cyclopentadiene. This result supports conclusions drawn from ab initio calculations of these states. The extensive Rydberg state-valence state mixing found in butadiene has bearing on previous interpretations of the electron energy loss spectrum of this molecule. RP MCDIARMID, R (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. NR 20 TC 26 Z9 26 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-2614 J9 CHEM PHYS LETT JI Chem. Phys. Lett. PD JAN 17 PY 1992 VL 188 IS 5-6 BP 423 EP 426 DI 10.1016/0009-2614(92)80841-X PG 4 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA HC636 UT WOS:A1992HC63600010 ER PT J AU AKSENTIJEVICH, S WHITFIELD, HJ YOUNG, WS WILDER, RL CHROUSOS, GP GOLD, PW STERNBERG, EM AF AKSENTIJEVICH, S WHITFIELD, HJ YOUNG, WS WILDER, RL CHROUSOS, GP GOLD, PW STERNBERG, EM TI ARTHRITIS-SUSCEPTIBLE LEWIS RATS FAIL TO EMERGE FROM THE STRESS HYPORESPONSIVE PERIOD SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Note DE CORTICOTROPIN-RELEASING HORMONE; FISCHER RAT; INSITU HYBRIDIZATION; ONTOGENY; INFLAMMATION; PARAVENTRICULAR NUCLEUS ID CORTICOTROPIN-RELEASING FACTOR; WALL-INDUCED ARTHRITIS; MESSENGER-RNA; EXPRESSION; PITUITARY; ONTOGENY; HORMONE; SYSTEM; INSITU AB Susceptibility to streptococcal cell wall (SCW)-induced arthritis in 4- to 6-week-old Lewis (LEW/N) rats is associated with blunted glucocorticoid production secondary to a profound defect in inflammatory mediator-induced hypothalamic corticotropin-releasing hormone (CRH) biosynthesis and secretion. The relative SCW arthritis resistance in histocompatible Fischer (F344/N) rats, on the other hand, is associated with robust hypothalamic-pituitary-adrenal (HPA) axis responses to inflammatory mediators. In this study, we investigated HPA axis responses to SCW during the postnatal developmental period in LEW/N and F344/N rats. We found that SCW-induced plasma corticosterone (CORT) responses do not significantly increase during development in LEW/N, while such responses clearly appear at postnatal day 14 in F344/N and outbred Harlan-Sprague-Dawley (HSD) rats. Additionally, LEW/N rats fail to exhibit the normal ontogenic increase in CRH mRNA levels in the paraventricular nucleus (PVN), whereas their SCW-induced PVN CRH mRNA responses are blunted compared to F344/N at postnatal day 14. Taken together, these results suggest that LEW/N rats fail to emerge completely from their stress hyporesponsive period. This may account for the lack of stress responsiveness in young adult LEW/N rats, and consequently, for their susceptibility to SCW-induced arthritis and other inflammatory diseases. C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,NEUROENDOCRINE IMMUNOL & BEHAV UNIT,BETHESDA,MD 20892. NATL INST CHILD HLTH & DEV,PEDIAT ENDOCRINOL BRANCH,BETHESDA,MD 20892. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NIAMS,ARTHRITIS & RHEUMATISM BRANCH,BETHESDA,MD 20892. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 NR 14 TC 35 Z9 35 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD JAN 17 PY 1992 VL 65 IS 1 BP 115 EP 118 DI 10.1016/0165-3806(92)90014-N PG 4 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA HC441 UT WOS:A1992HC44100013 ER PT J AU BARCHI, JJ MUSSER, S MARQUEZ, VE AF BARCHI, JJ MUSSER, S MARQUEZ, VE TI THE DECOMPOSITION OF 1-(BETA-D-RIBOFURANOSYL)-1,2-DIHYDROPYRIMIDIN-2-ONE (ZEBULARINE) IN ALKALI - MECHANISM AND PRODUCTS SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; MALONDIALDEHYDE; NUCLEOSIDES AB The mechanism of the base-catalyzed degradation of 1-(beta-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one (zebularine, 1a) and closely related analogues was studied by NMR spectroscopy and GC-MS. Addition of sodium deuteroxide to a solution of 1a in D2O effected a rapid and irreversible reaction characterized by complete degradation of the heterocyclic pyrimidinone ring. H-1 NMR data suggested that 1a was initially converted to the labile aldehyde 10. This was later confirmed by similar degradation of the 5-fluoro analogue 1b to the more stable aldehyde 9. The alkaline degradation of 1a reaches an end point after 4 h at room temperature with one identifiable product being the anomerized alpha-N1-O2 cyclic carbamate 6. Compound 6 was formed by degradation of both 1a and 1b. The ara epimer 1c formed the beta-carbamate 8, and the 5'-O-methyl derivative 1d proceeded to the 5-O-methyl carbamate 7. An inventory of the remaining atoms yields a formula which suggested the complementary component of the degradation to be an immediate precursor to 1,3-propane dialdehyde (malondialdehyde, MDA). Support for this proposal was evident in both the H-1 and C-13 NMR spectra of the basic reaction mixture which showed resonances that corresponded closely with those published for authentic MDA at pH 9.6. The presence of MDA was unequivocally proven by derivatization of the acidified degradation mixture with hydrazinobenzothiazole (HBT) to give the known adduct 11. GC-MS analysis of the adduct obtained from HBT and the MDA formed during the decomposition reaction was identical to the adduct prepared from authentic MDA and HBT. Since the 5'-O-methyl derivative 1d yielded the same type of products as those analogues with the 5'-hydroxyl free, it was concluded that the 5'-OH was not essential for alkaline lability. This contradicts the original literature assumption that some type of cyclization of the carbohydrate with the pyrimidinone system may be a first step in the mechanism. The data herein suggest that the base-catalyzed decomposition begins with the preferential attack at the 6-position of 2-pyrimidinone nucleosides. The discovery that a known mutagen (MDA) is a product in the degradation of 1a suggests that a relationship could exist between the chemical susceptibility of 1a and its unique biological activity. RP BARCHI, JJ (reprint author), NCI,DIV CANC TREATMENT,MED CHEM LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892, USA. RI Barchi Jr., Joseph/N-3784-2014 NR 24 TC 19 Z9 19 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD JAN 17 PY 1992 VL 57 IS 2 BP 536 EP 541 DI 10.1021/jo00028a026 PG 6 WC Chemistry, Organic SC Chemistry GA HA466 UT WOS:A1992HA46600026 ER PT J AU SMITH, RH WLADKOWSKI, BD HERLING, JA PFALTZGRAFF, TD PRUSKI, B KLOSE, J MICHEJDA, CJ AF SMITH, RH WLADKOWSKI, BD HERLING, JA PFALTZGRAFF, TD PRUSKI, B KLOSE, J MICHEJDA, CJ TI 1,3-DIALKYL-3-ACYLTRIAZENES - PRODUCTS AND RATES OF DECOMPOSITION IN ACIDIC AND NEUTRAL AQUEOUS-SOLUTIONS SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID 1,3-DIALKYLTRIAZENES; HYDROLYSIS; MECHANISM; KINETICS; AGENTS AB The products and mechanism of hydrolytic decomposition of a series of 1,3-dialkyl-3-acyltriazenes were studied in both acidic and neutral buffers. In the acidic region, the products are alkyl alcohols derived from the N(1) alkyl group and amides derived from the intact N(3) portion of the molecule. The solvent deuterium isotope effect (k(H2O)/k(D2O)) is less than 1.0. The mechanism is specific acid catalyzed, involving rapid reversible protonation of the 3-acyl group followed by scission of the N(2)-N(3) bond to generate an amide and an alkyl diazonium ion. The (2-hydroxyethyl)diazonium ion gives ethylene glycol and acetaldehyde, while the (2-chloroethyl)diazonium ion yields 2-chloroethanol. In the neutral region, the products are similar to those found in acidic buffers, alkyl alcohols, and amides. At this pH the (2-chloroethyl)diazonium ion produces ethylene glycol and acetaldehyde in addition to 2-chloroethanol. The solvent deuterium isotope effect (k(H2O)/k(D2O)) is greater than 1.0. The mechanism involves unimolecular heterolysis of the N(2)-N(3) bond to form an amide anion and an alkyldiazonium ion. The methyldiazonium ion leads to incorporation of deuterium in the methyl group of the products, indicating the existence of an equilibrium between the metastable methyldiazonium ion and diazomethane. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BAS RES PROGRAM,MOLEC ASPECTS DRUG DESIGN SECT,FREDERICK,MD 21702. RP SMITH, RH (reprint author), WESTERN MARYLAND COLL,DEPT CHEM,WESTMINSTER,MD 21157, USA. NR 18 TC 25 Z9 25 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD JAN 17 PY 1992 VL 57 IS 2 BP 654 EP 661 DI 10.1021/jo00028a047 PG 8 WC Chemistry, Organic SC Chemistry GA HA466 UT WOS:A1992HA46600047 ER PT J AU TAKAHASHI, H NAKAGAWA, Y PENDLETON, CD HOUGHTEN, RA YOKOMURO, K GERMAIN, RN BERZOFSKY, JA AF TAKAHASHI, H NAKAGAWA, Y PENDLETON, CD HOUGHTEN, RA YOKOMURO, K GERMAIN, RN BERZOFSKY, JA TI INDUCTION OF BROADLY CROSS-REACTIVE CYTOTOXIC T-CELLS RECOGNIZING AN HIV-1 ENVELOPE DETERMINANT SO SCIENCE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIBODIES; NEUTRALIZATION; CHIMPANZEES; INFECTION; PEPTIDES; MOLECULE; GP160; LYMPHOCYTES; RECOGNITION AB An immunodominant determinant for cytotoxic T lymphocytes (CTLs) exists in the hypervariable portion of human immunodeficiency virus-1 (HIV-1) gp160. Three mouse CTL lines (specific for isolates MN, RF, and IIIB) were examined for recognition of homologous determinants from distinct isolates. Only MN-elicited CTLs showed extensive interisolate cross-reactivity. Residue 325 played a critical role in specificity, with MN-elicited CTLs responding to peptides with an aromatic or cyclic residue and IIIB-induced cells recognizing peptides with an aliphatic residue at this position. CTL populations with broad specificities were generated by restimulation of IIIB-gp160 primed cells with MN-type peptides that have an aliphatic substitution at 325. This represents an approach to synthetic vaccines that can generate broadly cross-reactive CTLs capable of effector function against a wide range of HIV isolates. C1 TORREY PINES INST MOLEC STUDIES,SAN DIEGO,CA 92121. NIAID,IMMUNOL LAB,LYMPHOCYTE BIOL SECT,BETHESDA,MD 20892. NCI,METAB BRANCH,MOLEC IMMUNOGENET & VACCINE RES SECT,BETHESDA,MD 20892. RP TAKAHASHI, H (reprint author), NIPPON MED COLL,DEPT MICROBIOL & IMMUNOL,1-1-5 SENDAGI,BUNKYO KU,TOKYO 113,JAPAN. NR 28 TC 143 Z9 143 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JAN 17 PY 1992 VL 255 IS 5042 BP 333 EP 336 DI 10.1126/science.1372448 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GZ695 UT WOS:A1992GZ69500043 PM 1372448 ER PT J AU FELSENFELD, G AF FELSENFELD, G TI CHROMATIN AS AN ESSENTIAL PART OF THE TRANSCRIPTIONAL MECHANISM SO NATURE LA English DT Review ID BETA-GLOBIN GENE; DOMINANT CONTROL REGION; RNA POLYMERASE-II; LOCUS ACTIVATION REGION; HIGHER-ORDER STRUCTURE; SILENT MATING LOCI; SACCHAROMYCES-CEREVISIAE; HYPERSENSITIVE SITES; PREINITIATION COMPLEXES; POSITIONED NUCLEOSOMES AB The increasingly detailed biochemical definition of the protein complexes that regulate gene transcription has led to the re-emergence of questions about the role of histones. Much recent evidence suggests that transcriptional activation requires that transcription factors successfully compete with histones for binding to promoters, and that there may be more than one mechanism by which this is achieved. RP FELSENFELD, G (reprint author), NIH, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. NR 87 TC 805 Z9 807 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 16 PY 1992 VL 355 IS 6357 BP 219 EP 224 DI 10.1038/355219a0 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GZ694 UT WOS:A1992GZ69400055 PM 1731219 ER PT J AU WHITCUP, SM BUTLER, KM CARUSO, R DESMET, MD RUBIN, B HUSSON, RN LOPEZ, JS BELFORT, R PIZZO, PA NUSSENBLATT, RB AF WHITCUP, SM BUTLER, KM CARUSO, R DESMET, MD RUBIN, B HUSSON, RN LOPEZ, JS BELFORT, R PIZZO, PA NUSSENBLATT, RB TI RETINAL TOXICITY IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED CHILDREN TREATED WITH 2',3'-DIDEOXYINOSINE SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID THIORIDAZINE AB To assess the safety and antiretroviral activity of 2',3'-dideoxyinosine, we enrolled 43 children with symptomatic (Centers for Disease Control class P-2) human immunodeficiency virus infection in a Phase I-II study and monitored them prospectively for the development of ocular complications secondary to HIV infection or drug toxicity. Follow-up ranged from 12 to 103 weeks with a median follow-up of 71 weeks. Three of 43 children (7.0%) developed peripheral atrophy of the retinal pigment epithelium during treatment with 2',3'-dideoxyinosine. The two children with the most severe retinal atrophy were enrolled in the study at the highest dosage studied (540 mg/m2/day). In contrast to findings in children, no retinal atrophy in HIV-infected adults treated with 2',3'-dideoxyinosine has been evident to date. C1 NEI,OPHTHALM GENET SERV,BETHESDA,MD 20892. NEI,CLIN SERV,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. RP WHITCUP, SM (reprint author), NEI,IMMUNOL LAB,BLDG 10,RM 10N202,BETHESDA,MD 20892, USA. RI Belfort Jr, Rubens/E-2252-2012; OI Belfort Jr, Rubens/0000-0002-8422-3898; de Smet, Marc/0000-0002-9217-5603 NR 20 TC 42 Z9 42 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JAN 15 PY 1992 VL 113 IS 1 BP 1 EP 7 PG 7 WC Ophthalmology SC Ophthalmology GA GY181 UT WOS:A1992GY18100001 PM 1728133 ER PT J AU STEFANSSON, E MACHEMER, R DEJUAN, E MCCUEN, BW PETERSON, J AF STEFANSSON, E MACHEMER, R DEJUAN, E MCCUEN, BW PETERSON, J TI RETINAL OXYGENATION AND LASER TREATMENT IN PATIENTS WITH DIABETIC-RETINOPATHY SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID PHOTOCOAGULATION; TENSION AB The oxygen tension in the preretinal vitreous cavity was measured in human patients undergoing vitreous operations for proliferative diabetic retinopathy. The oxygen tension was significantly higher (P = .004) over areas of retina that had been treated with panretinal photocoagulation than it was over untreated areas in the same retina. This confirmed previous results in animals that showed that panretinal photocoagulation increases the inner retinal oxygen tension. We concluded that panretinal photocoagulation improves the oxygen supply to the inner retina and thereby minimizes the influence of retinal ischemia in diabetic retinopathy. C1 DUKE UNIV,CTR EYE,DURHAM,NC 27706. NIH,BETHESDA,MD 20892. RP STEFANSSON, E (reprint author), UNIV ICELAND,LANDAKOTSSPITALI,DEPT OPHTHALMOL,IS-101 REYKJAVIK,ICELAND. FU PHS HHS [R01-7001] NR 9 TC 105 Z9 108 U1 0 U2 4 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JAN 15 PY 1992 VL 113 IS 1 BP 36 EP 38 PG 3 WC Ophthalmology SC Ophthalmology GA GY181 UT WOS:A1992GY18100007 PM 1728144 ER PT J AU BUCHWALD, D CHENEY, PR PETERSON, DL HENRY, B WORMSLEY, SB GEIGER, A ABLASHI, DV SALAHUDDIN, SZ SAXINGER, C BIDDLE, R KIKINIS, R JOLESZ, FA FOLKS, T BALACHANDRAN, N PETER, JB GALLO, RC KOMAROFF, AL AF BUCHWALD, D CHENEY, PR PETERSON, DL HENRY, B WORMSLEY, SB GEIGER, A ABLASHI, DV SALAHUDDIN, SZ SAXINGER, C BIDDLE, R KIKINIS, R JOLESZ, FA FOLKS, T BALACHANDRAN, N PETER, JB GALLO, RC KOMAROFF, AL TI A CHRONIC ILLNESS CHARACTERIZED BY FATIGUE, NEUROLOGIC AND IMMUNOLOGICAL DISORDERS, AND ACTIVE HUMAN HERPESVIRUS TYPE-6 INFECTION SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE FATIGUE SYNDROME, CHRONIC; HERPESVIRUS-6, HUMAN; NEUROLOGIC MANIFESTATIONS; FATIGUE; IMMUNOLOGICAL DISEASES ID BARR VIRUS-INFECTION; CHRONIC MONONUCLEOSIS SYNDROME; NATURAL-KILLER CELLS; MAGNETIC-RESONANCE; HUMAN-LYMPHOCYTES; SYNDROME AIDS; HUMAN-DISEASE; T-CELLS; HHV-6; HBLV AB Objective: To conduct neurologic, immunologic, and virologic studies in patients with a chronic debilitating illness of acute onset. Design: Cohort study with comparison to matched, healthy control subjects. Patients: We studied 259 patients who sought care in one medical practice; 29% of the patients were regularly bedridden or shut-in. Main Outcome Measures: Detailed medical history, physical examination, conventional hematologic and chemistry testing, magnetic resonance imaging (MRI) studies lymphocyte phenotyping studies, and assays for active infection of patients' lymphocytes with human herpesvirus type 6 (HHV-6). Main Results: Patients had a higher mean (+/- SD) CD4/CD8 T-cell ratio than matched healthy controls (3.16 +/- 1.5 compared with 2.3 +/- 1.0, respectively; P < 0.003). Magnetic resonance scans of the brain showed punctate, subcortical areas of high signal intensity consistent with edema or demyelination in 78% of patients (95% Cl, 72% to 86%) and in 21% of controls (Cl, 11% to 36%) (P < 10(-9)). Primary cell culture of lymphocytes showed active replication of HHV-6 in 79 of 113 patients (70%; Cl, 61% to 78%) and in 8 of 40 controls (20%; Cl, 9% to 36%) (P < 10(-8)), a finding confirmed by assays using monoclonal antibodies specific for HHV-6 proteins and by polymerase chain reaction assays specific for HHV-6 DNA. Conclusions: Neurologic symptoms, MRI findings, and lymphocyte phenotyping studies suggest that the patients may have been experiencing a chronic, immunologically mediated inflammatory process of the central nervous system. The active replication of HHV-6 most likely represents reactivation of latent infection, perhaps due to immunologic dysfunction. Our study did not directly address whether HHV-6, a lymphotropic and gliotropic virus, plays a role in producing the symptoms or the immunologic and neurologic dysfunction seen in this illness. Whether the findings in our patients, who came from a relatively small geographic area, will be generalizable to other patients with a similar syndrome remains to be seen. C1 BRIGHAM & WOMENS HOSP,DEPT MED,DIV GEN MED,75 FRANCIS ST,BOSTON,MA 02115. UNIV WASHINGTON,HARBORVIEW MED CTR,SEATTLE,WA 98104. WASHOE CTY SHERIFFS DIV,DIV FORENS SCI,RENO,NV 89512. CYTOMETRY ASSOCIATES,SAN DIEGO,CA 92121. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. UNIV SO CALIF,HUNTINGTON MEM HOSP,AIDS RES LAB,PASADENA,CA 91105. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. STOCKTON RADIOL MED GRP,STOCKTON,CA 95204. CTR DIS CONTROL,DIV VIROL,ATLANTA,GA 30333. UNIV KANSAS,MED CTR,DEPT MICROBIOL,KANSAS CITY,KS 66103. SPECIALTY LABS INC,SANTA MONICA,CA 90009. FU NIAID NIH HHS [R01AI26788, R01AI27314, U01AI32246] NR 70 TC 260 Z9 264 U1 1 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 15 PY 1992 VL 116 IS 2 BP 103 EP 113 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA GZ356 UT WOS:A1992GZ35600002 PM 1309285 ER PT J AU WALDMANN, TA PASTAN, IH GANSOW, OA JUNGHANS, RP AF WALDMANN, TA PASTAN, IH GANSOW, OA JUNGHANS, RP TI THE MULTICHAIN INTERLEUKIN-2 RECEPTOR - A TARGET FOR IMMUNOTHERAPY SO ANNALS OF INTERNAL MEDICINE LA English DT Discussion DE RECEPTORS, INTERLEUKIN-2; IMMUNOTHERAPY; INTERLEUKIN-2; LYMPHOCYTES-T; LYMPHOKINES ID T-CELL LEUKEMIA; CARDIAC ALLOGRAFT SURVIVAL; GROWTH-FACTOR RECEPTOR; ANTI-TAC ANTIBODY; MONOCLONAL-ANTIBODY; PSEUDOMONAS EXOTOXIN; IL-2 RECEPTOR; HUMANIZED ANTIBODY; INFECTED-CELLS; FUSION PROTEIN AB Activation of resting T-lymphocytes induces synthesis of interleukin-2 (IL-2) and expression of cell surface receptors for this lymphokine. In contrast to resting normal T-cells that do not express high-affinity IL-2 receptors (IL-2R), abnormal T-cells of patients with leukemia-lymphoma, certain autoimmune disorders, and individuals rejecting allografts express this receptor. Exploiting this difference in receptor expression, antibodies to the IL-2 receptor have been used effectively to treat patients with leukemia and lymphoma. One approach is to use monoclonal antibodies produced in mice; the disadvantage is that they are highly immunogenic. In an effort to reduce the immunogenicity of the mouse monoclonal antibodies, monoclonal-antibody-mediated therapy has been revolutionized by generating humanized antibodies produced by genetic engineering in which the molecule is human except for the antigen-combining regions, which are retained from the mouse. Further, to increase its cytotoxic effectiveness, the monoclonal antibody has been armed with toxins or radionuclides. Alternatively, IL-2 itself has been linked to a toxin to kill IL-2 receptor-bearing cells. Thus, IL-2 receptor-directed therapy provides a new method for treating certain neoplastic diseases and autoimmune disorders and for preventing allograft rejection. C1 NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NCI,RADIAT ONCOL BRANCH,INORGAN & RADIOIMMUNE CHEM SECT,BETHESDA,MD 20892. HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA 02215. RP WALDMANN, TA (reprint author), NCI,METAB BRANCH,BLDG 10,ROOM 4N115,BETHESDA,MD 20892, USA. NR 79 TC 95 Z9 95 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 JAN 15 PY 1992 VL 116 IS 2 BP 148 EP 160 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA GZ356 UT WOS:A1992GZ35600008 PM 1727619 ER PT J AU YARCHOAN, R TSIATIS, AA BRODER, S AF YARCHOAN, R TSIATIS, AA BRODER, S TI CD4 COUNTS AND HIV-RELATED DEATHS - REPLY SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP YARCHOAN, R (reprint author), NCI,BETHESDA,MD 20892, USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 15 PY 1992 VL 116 IS 2 BP 169 EP 170 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA GZ356 UT WOS:A1992GZ35600015 ER PT J AU RAMPINO, NJ AF RAMPINO, NJ TI CISPLATIN INDUCED ALTERATIONS IN ORIENTED FIBERS OF DNA STUDIES BY ATOMIC FORCE MICROSCOPY SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CIS-DIAMMINEDICHLOROPLATINUM(II); OLIGONUCLEOTIDE; ADDUCTS RP RAMPINO, NJ (reprint author), NICHHD,LTPB,MACROMOLEC ANAL SECT,BETHESDA,MD 20892, USA. NR 17 TC 8 Z9 8 U1 1 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 15 PY 1992 VL 182 IS 1 BP 201 EP 207 DI 10.1016/S0006-291X(05)80131-7 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GZ992 UT WOS:A1992GZ99200029 PM 1731780 ER PT J AU SIDRANSKY, E GINNS, EI FRENKEL, E BENEAR, JB AF SIDRANSKY, E GINNS, EI FRENKEL, E BENEAR, JB TI ANEMIC GAUCHER PATIENTS WITH ELEVATED ENDOGENOUS ERYTHROPOIETIN LEVELS MAY NOT RESPOND TO RECOMBINANT ERYTHROPOIETIN THERAPY SO BLOOD LA English DT Letter C1 UNIV TEXAS,SW MED CTR,DALLAS,TX 75230. CANC CARE ASSOCIATES,TULSA,OK. RP SIDRANSKY, E (reprint author), NIH,CLIN NEUROSCI BRANCH,MOLEC NEUROGENET SECT,BETHESDA,MD 20892, USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JAN 15 PY 1992 VL 79 IS 2 BP 532 EP 533 PG 2 WC Hematology SC Hematology GA GZ357 UT WOS:A1992GZ35700034 PM 1730096 ER PT J AU BOICE, JD MANDEL, JS DOODY, MM YODER, RC MCGOWAN, R AF BOICE, JD MANDEL, JS DOODY, MM YODER, RC MCGOWAN, R TI A HEALTH SURVEY OF RADIOLOGIC TECHNOLOGISTS SO CANCER LA English DT Article ID CORONARY HEART-DISEASE; ORAL-CONTRACEPTIVE USE; PERMANENT HAIR-DYES; BREAST-CANCER; MYOCARDIAL-INFARCTION; CIGARETTE-SMOKING; RELATIVE WEIGHT; RISK; WOMEN; MORTALITY AB A health survey of more than 143,000 radiologic technologists is described. The population was identified from the 1982 computerized files of the American Registry of Radiologic Technologists, which was established in 1926. Inactive members were traced to obtain current addresses or death notifications. More than 6000 technologists were reported to have died. For all registrants who were alive when located, a detailed 16-page questionnaire was sent, covering occupational histories, medical conditions, and other personal and lifestyle characteristics. Nonrespondents were contacted by telephone to complete an abbreviated questionnaire. More than 104,000 responses were obtained. The overall response rate was 79%. Most technologists were female (76%), white (93%), and employed for an average of 12 years; 37% attended college, and approximately 50% never smoked cigarettes. Radiation exposure information was sought from employer records and commercial dosimetry companies. Technologists employed for the longest times had the highest estimated cumulative exposures, with approximately 9% with exposures greater than 5 cGy. There was a high correlation between cumulative occupational exposure and personal exposure to medical radiographs, related, in part, to the association of both factors with attained age. It is interesting that 10% of all technologists allowed others to practice taking radiographs on them during their training. Nearly 4% of the respondents reported having some type of cancer, mainly of the skin (1517), breast (665), and cervix (726). Prospective surveys will monitor cancer mortality rates through use of the National Death Index and cancer incidence through periodic mailings of questionnaires. This is the only occupational study of radiation employees who are primarily women and should provide new information on the possible risks associated with relatively low levels of exposure. C1 TECH OPS LANDAUER INC,GLENWOOD,IL. AMER REGISTRY RADIOL TECHNOLOGISTS,MENDOTA HTS,MN. UNIV MINNESOTA,SCH PUBL HLTH,DIV ENVIRONM & OCCUPAT HLTH,MINNEAPOLIS,MN 55455. RP BOICE, JD (reprint author), NCI,RADIAT EPIDEMIOL BRANCH,6130 EXECUT BLVD,SUITE 408,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CP-21015, N01-CP-61006, N01-CP-81058] NR 44 TC 69 Z9 70 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JAN 15 PY 1992 VL 69 IS 2 BP 586 EP 598 DI 10.1002/1097-0142(19920115)69:2<586::AID-CNCR2820690251>3.0.CO;2-3 PG 13 WC Oncology SC Oncology GA GY837 UT WOS:A1992GY83700050 PM 1728391 ER PT J AU BARR, RD MAGRATH, IT AF BARR, RD MAGRATH, IT TI HODGKINS-DISEASE IN CHILDREN 4 YEARS OF AGE OR YOUNGER SO CANCER LA English DT Letter C1 NCI,PEDIAT ONCOL BRANCH,BETHESDA,MD 20892. RP BARR, RD (reprint author), MCMASTER UNIV,DEPT PEDIAT,HAMILTON L8S 4L8,ONTARIO,CANADA. NR 7 TC 3 Z9 3 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 JAN 15 PY 1992 VL 69 IS 2 BP 601 EP 602 PG 2 WC Oncology SC Oncology GA GY837 UT WOS:A1992GY83700053 PM 1728394 ER PT J AU SAFTLAS, AF OLSON, DR HOOVER, RN BRINTON, LA SZKLO, M AF SAFTLAS, AF OLSON, DR HOOVER, RN BRINTON, LA SZKLO, M TI MAMMOGRAPHIC PARENCHYMAL PATTERNS AND FAMILY HISTORY OF BREAST-CANCER - REPLY SO CANCER LA English DT Letter C1 CTR DIS CONTROL,NIOSH,OFF DIRECTOR,ATLANTA,GA 30333. NCI,DIV CANC ETIOL,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21218. RP SAFTLAS, AF (reprint author), CTR DIS CONTROL,NATL CTR CHRON DIS PREVENT,DIV REP HLTH,ATLANTA,GA 30333, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 2 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JAN 15 PY 1992 VL 69 IS 2 BP 603 EP 603 PG 1 WC Oncology SC Oncology GA GY837 UT WOS:A1992GY83700055 ER PT J AU MCLAUGHLIN, JK SILVERMAN, DT HSING, AW ROSS, RK SCHOENBERG, JB YU, MC STEMHAGEN, A LYNCH, CF BLOT, WJ FRAUMENI, JF AF MCLAUGHLIN, JK SILVERMAN, DT HSING, AW ROSS, RK SCHOENBERG, JB YU, MC STEMHAGEN, A LYNCH, CF BLOT, WJ FRAUMENI, JF TI CIGARETTE-SMOKING AND CANCERS OF THE RENAL PELVIS AND URETER SO CANCER RESEARCH LA English DT Article ID RISK-FACTORS; ANALGESICS; BLADDER AB A population-based case-control study of renal pelvis and ureter cancers (502 cases, 496 controls) conducted in three areas of the United States found cigarette smoking to be associated with a 3.1-fold increase in risk, with long-term (> 45 years) smokers having a 7.2-fold increased risk. Statistically significant dose-response associations were observed for both cancer sites and in both sexes regardless of the measure used: cigarettes per day, duration of use, or pack years. A significant decreasing trend in risk with increasing years quit smoking was also demonstrated for these cancers. Attributable risk estimates indicate that approximately 7 of 10 cancers of the renal pelvis and ureter among men and almost 4 of 10 among women are caused by smoking. The results of this study, the largest to date, confirm that cigarette smoking is the major cause of cancers of the renal pelvis and ureter, and that cessation of smoking could eliminate a large proportion of these tumors. C1 UNIV SO CALIF,SCH MED,DEPT PREVENT MED,LOS ANGELES,CA 90033. NEW JERSEY DEPT HLTH,TRENTON,NJ 08625. UNIV IOWA,COLL MED,DEPT PREVENT MED & ENVIRONM HLTH,IOWA CITY,IA 52242. RP MCLAUGHLIN, JK (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,ROOM 415,BETHESDA,MD 20892, USA. NR 18 TC 74 Z9 75 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1992 VL 52 IS 2 BP 254 EP 257 PG 4 WC Oncology SC Oncology GA GZ693 UT WOS:A1992GZ69300002 PM 1728398 ER PT J AU WALKER, C BERMUDEZ, E STEWART, W BONNER, J MOLLOY, CJ EVERITT, J AF WALKER, C BERMUDEZ, E STEWART, W BONNER, J MOLLOY, CJ EVERITT, J TI CHARACTERIZATION OF PLATELET-DERIVED GROWTH-FACTOR AND PLATELET-DERIVED GROWTH-FACTOR RECEPTOR EXPRESSION IN ASBESTOS-INDUCED RAT MESOTHELIOMA SO CANCER RESEARCH LA English DT Article ID FACTOR A-CHAIN; CELL-LINES; MALIGNANT MESOTHELIOMA; PDGF RECEPTOR; GENES; ALPHA; ISOFORMS; TUMORS; BETA AB Although altered expression of platelet-derived growth factor (PDGF) is a hallmark of human mesothelioma, expression of PDGF receptors has not been characterized in this cell type. In addition, the expression of this growth factor and its cognate receptor in rodent mesothelioma has not been investigated. In this study, examination of transformed mesothelial cells derived from asbestos-induced rat mesotheliomas revealed that these cells expressed high affinity PDGF receptors (K(d) = 0.5 nM) and receptor number was 1.6 x 10(5)/cell. Western analysis using antibodies specific for either the alpha-type or beta-type PDGF receptor and Northern analysis using probes specific for alpha- and beta-type receptor RNA transcripts indicated that these cells expressed beta-type PDGF receptors but that alpha-type receptors could not be detected. However, when the mesothelioma-derived cells were examined for the expression of PDGF, no expression of this growth factor could be detected. The transformed cells expressed no detectable A- or B-chain PDGF RNA transcripts; and using a competitive enzyme immunoassay specific for isoforms containing the B chain of PDGF and a sandwich enzyme-linked immunosorbent assay specific for A-chain-containing isoforms, neither AA, nor AB, nor BB isoforms of this growth factor could be detected in medium conditioned by these cells. The absence of alterations in PDGF expression in rat mesothelioma, in contrast to the data for the human disease, suggests that the production of this growth factor by transformed mesothelial cells may be species specific. C1 NIEHS,RES TRIANGLE PK,NC 27709. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,PRINCETON,NJ 08543. RP WALKER, C (reprint author), CHEM IND INST TOXICOL,RES TRIANGLE PK,NC 27709, USA. RI Molloy, Christopher/A-6821-2013 OI Molloy, Christopher/0000-0003-2964-6166 NR 33 TC 32 Z9 32 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1992 VL 52 IS 2 BP 301 EP 306 PG 6 WC Oncology SC Oncology GA GZ693 UT WOS:A1992GZ69300011 PM 1309438 ER PT J AU ANGLARD, P TRAHAN, E LIU, S LATIF, F MERINO, MJ LERMAN, MI ZBAR, B LINEHAN, WM AF ANGLARD, P TRAHAN, E LIU, S LATIF, F MERINO, MJ LERMAN, MI ZBAR, B LINEHAN, WM TI MOLECULAR AND CELLULAR CHARACTERIZATION OF HUMAN RENAL-CELL CARCINOMA CELL-LINES SO CANCER RESEARCH LA English DT Article ID VONHIPPEL-LINDAU DISEASE; GROWTH-FACTOR; HUMAN DNA; HUMAN CHROMOSOME-3; HUMAN-KIDNEY; SHORT ARM; TUMORS; CANCER; ESTABLISHMENT; LOCALIZATION AB Recent studies have suggested that a tumor suppressor gene located in the region 3p21-26 of chromosome 3 is essential to the genesis of sporadic renal cell carcinoma (RCC) and that other tumor suppressor genes located on other chromosomes may be involved with progression of this malignancy. The cellular heterogeneity of solid tumors complicates their analysis. In order to analyze a homogeneous population of tumor cells and identify genetic changes associated with histology in renal cortical tumors, we have established and characterized 35 RCC lines derived from tumor tissue from 31 patients with renal cell carcinomas. The overall success rate in establishing these cell lines from fresh or frozen specimens was 75% (18 of 24) and 35% (17 of 48), respectively. These lines differed in their morphology, growth rates, and tumorigenicity in athymic nude mice. Molecular characterization utilizing DNA fingerprinting and restriction fragment length polymorphism deletion analysis was performed to detect somatic mutations and loss of heterozygosity on the short arm of chromosome 3. Analysis revealed loss of heterozygosity on chromosome 3p in 25 cell lines derived from 28 informative nonpapillary forms of RCC (89%). Deletion-mapping analysis showed the retention of the distal locus, D3S18, in one of the RCC cell lines, which further localized the position of the putative tumor suppressor gene to the region proximal to D3S18. Although deletions on chromosome 3 have been recently suggested to be specific to the clear cell-type phenotype, our results revealed no correlation between loss of heterozygosity and clear or granular cell types. C1 NCI,SURG BRANCH,UROL ONCOL SECT,BLDG 10,ROOM 2B47,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES FACIL,IMMUNOBIOL LAB,FREDERICK,MD 21701. NCI,DIV CANC BIOL & DIAG,FREDERICK,MD 21701. NR 46 TC 84 Z9 84 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1992 VL 52 IS 2 BP 348 EP 356 PG 9 WC Oncology SC Oncology GA GZ693 UT WOS:A1992GZ69300018 PM 1345811 ER PT J AU SHOCKLEY, TR LIN, K SUNG, C NAGY, JA TOMPKINS, RG DEDRICK, RL DVORAK, HF YARMUSH, ML AF SHOCKLEY, TR LIN, K SUNG, C NAGY, JA TOMPKINS, RG DEDRICK, RL DVORAK, HF YARMUSH, ML TI A QUANTITATIVE-ANALYSIS OF TUMOR SPECIFIC MONOCLONAL-ANTIBODY UPTAKE BY HUMAN-MELANOMA XENOGRAFTS - EFFECTS OF ANTIBODY IMMUNOLOGICAL PROPERTIES AND TUMOR-ANTIGEN EXPRESSION LEVELS SO CANCER RESEARCH LA English DT Article ID SOLID TUMORS; RADIOLABELED ANTIBODIES; CARCINOMA XENOGRAFTS; IMMUNOGLOBULIN-G; COLON-CARCINOMA; BLOOD-FLOW; LOCALIZATION; CELLS; BIODISTRIBUTION; KINETICS AB The time-dependent (5 min-72 h) localization of 3 radiolabeled antimelanoma monoclonal antibodies (MAbs 436, IND1, and 9.2.27) was studied in paired label experiments in small (4-12 mg) s.c. human melanoma xenografts (SK-MEL-2 and M21) in athymic nude mice. MAb 436 recognizes a M(r) 125,000 cell surface melanoma-associated glycoprotein antigen (125 kDa-MAA); MAbs IND1 and 9.2.27 recognize a high molecular weight melanoma-associated antigen, but with equilibrium association constants differing by 2 orders of magnitude (10(8)-10(10) M-1). The two tumors were found to differ in their antigen expression levels and in both interstitial and vascular volumes. Accumulation of MAbs in both tumors was determined primarily by antigen expression levels and also by physiological factors such as vascular permeability and vascular volume; at the dose administered (20-mu-g/mouse), differences in MAb affinity among specific MAbs had minimal effect on accumulation. Quantitative flow cytometry measurements showed that antigen expression in vivo differed from that of cultured tumor cells. In vivo, expression of the M(r) 125,000 MAA decreased by a factor of about 2.5 in both tumors. In contrast, the in vivo expression of the high molecular weight MAA decreased in M21 tumors but increased by 2.0-3.5-fold in SK-MEL-2 tumors. Data were analyzed using a three-compartment pharmacokinetic model (C. Sung et al., Cancer Res., 52:377-384,1992) to provide plasma-to-tissue transport constants (k), the interstitial fluid flow rate (L), and estimates of the in vivo interstitial MAb binding site concentration (B(o)). For all MAbs, the plasma-to-tissue transport constants were consistently greater for M21 tumors (0.44-0.85-mu-l/min/g) than for SK-MEL-2 tumors (0.28-0.66-mu-l/min/g), and values of k for both tumors were approximately 1 order of magnitude greater than those for skeletal muscle (0.06-0.08-mu-l/min/g). The model-estimated binding site concentration of melanoma-specific antibodies was 15-70 times lower than that predicted by experimental measurements of tumor antigen concentrations. Factors that may contribute to this discrepancy include inaccessibility of tumor cell binding sites to MAb and MAb catabolism. In summary, these results indicate that, for the MAb dose used in this study, variables pertaining to the tumor target (ie., antigen expression levels, vascular volume, and vascular permeability) are the most important for determining MAb accumulation in tumors. C1 RUTGERS STATE UNIV,DEPT CHEM & BIOCHEM ENGN,PISCATAWAY,NJ 08854. RUTGERS STATE UNIV,CTR ADV BIOTECHNOL & MED,PISCATAWAY,NJ 08854. MIT,DEPT CHEM ENGN,CAMBRIDGE,MA 02139. BETH ISRAEL HOSP,DEPT PATHOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. BETH ISRAEL HOSP,CHARLES A DANA RES INST,BOSTON,MA 02215. NIH,BIOMED ENGN & INSTRUMENTAT BRANCH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. FU NCI NIH HHS [CA-50453, CA-28471] NR 59 TC 70 Z9 70 U1 2 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 JAN 15 PY 1992 VL 52 IS 2 BP 357 EP 366 PG 10 WC Oncology SC Oncology GA GZ693 UT WOS:A1992GZ69300019 PM 1728407 ER PT J AU SUNG, C SHOCKLEY, TR MORRISON, PF DVORAK, HF YARMUSH, ML DEDRICK, RL AF SUNG, C SHOCKLEY, TR MORRISON, PF DVORAK, HF YARMUSH, ML DEDRICK, RL TI PREDICTED AND OBSERVED EFFECTS OF ANTIBODY-AFFINITY AND ANTIGEN DENSITY ON MONOCLONAL-ANTIBODY UPTAKE IN SOLID TUMORS SO CANCER RESEARCH LA English DT Article ID BINDING; PROTEIN; MICE; BIODISTRIBUTION; XENOGRAFTS; KINETICS; MELANOMA; TISSUE; LOCALIZATION; DEGRADATION AB The uptake and binding of monoclonal antibodies (MAbs) in solid tumors after a bolus i.v. injection are described using a compartmental pharmacokinetic model. The model assumes that MAb permeates into tumor unidirectionally from plasma across capillaries and clears from tumor by interstitial fluid flow and that interstitial antibody-antigen interactions are characterized by the Langmuir isotherm for reversible, saturable binding. Typical values for plasma clearance and tumor capillary permeability of a MAb and for interstitial fluid flow and interstitial volume fraction of a solid tumor were used to simulate the uptake of MAbs at various values of the binding affinity or antigen density for a range of MAb doses. The model indicates that at low doses, an increase in binding affinity may lead to an increase in MAb uptake. On the other hand, at doses approaching saturation of antigen or when uptake is permeation limited, an increase in the binding affinity from moderate to high affinity will have only a small effect on increasing MAb uptake. The model also predicts that an increase in antigen density will greatly increase MAb uptake when uptake is not permeation limited. Our experiments on MAb uptake in melanoma tumors in athymic mice after injection of 20-mu-g MAb (initial plasma concentration, about 120 nm) are consistent with these model-based conclusions. Two MAbs differing in affinity by more than 2 orders of magnitude (3.8 x 10(8) M-1 and 5 x 10(10) M-1) but with similar in vivo antigen densities in M21 melanoma attained similar concentrations in the tumor. Two MAbs of similar affinity but having a 3-fold difference in in vivo antigen density in SK-MEL-2 melanoma showed that the MAb targeted to the more highly expressed antigen attained a higher MAb concentration. We also discuss the model predictions in relation to other experiments reported in the literature. The theoretical and experimental findings suggest that, for high dose applications, efforts to increase MAb uptake in a tumor should emphasize the identification of an abundantly expressed antigen on tumor cells more than the selection of a very high affinity MAb. C1 MIT,DEPT CHEM ENGN,CAMBRIDGE,MA 02139. BETH ISRAEL HOSP,DEPT PATHOL,BOSTON,MA 02215. BETH ISRAEL HOSP,CHARLES A DANA RES INST,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RUTGERS STATE UNIV,DEPT CHEM & BIOCHEM ENGN,PISCATAWAY,NJ 08854. RUTGERS STATE UNIV,CTR ADV BIOTECHNOL & MED,PISCATAWAY,NJ 08854. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP SUNG, C (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892, USA. NR 28 TC 79 Z9 79 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1992 VL 52 IS 2 BP 377 EP 384 PG 8 WC Oncology SC Oncology GA GZ693 UT WOS:A1992GZ69300021 PM 1728409 ER PT J AU SCHULZ, N PROPST, F ROSENBERG, MP LINNOILA, RI PAULES, RS KOVATCH, R OGISO, Y VANDEWOUDE, G AF SCHULZ, N PROPST, F ROSENBERG, MP LINNOILA, RI PAULES, RS KOVATCH, R OGISO, Y VANDEWOUDE, G TI PHEOCHROMOCYTOMAS AND C-CELL THYROID NEOPLASMS IN TRANSGENIC C-MOS MICE - A MODEL FOR THE HUMAN MULTIPLE ENDOCRINE NEOPLASIA TYPE-2 SYNDROME SO CANCER RESEARCH LA English DT Article ID PROTO-ONCOGENE PRODUCT; DETERMINES METHYLATION; MEIOTIC MATURATION; MOUSE-TISSUES; EXPRESSION; CHROMOSOME-10; TRANSCRIPTS; MECHANISM; OOCYTES AB Transgenic mice carrying and expressing a mos protooncogene, linked to the Moloney murine sarcoma virus long terminal repeat, develop severe neurological defects and lens abnormalities. Here we report that after long latent periods, mice in three of four of these mos transgenic lines develop a high frequency of multicentric pheochromocytomas and/or medullary thyroid neoplasms. The pattern of tumor formation is remarkably similar to the human autosomal dominantly inherited neoplastic syndrome, multiple endocrine neoplasia type 2 (MEN 2), and tumors from these transgenic animals display the same neuroendocrine marker staining pattern as seen in MEN 2. The similarity between the tumor pathologies and presentation patterns of MEN 2 patients and mos transgenic mice suggests that they may arise through related pathways. The type of tumor presentation varies in a line-dependent manner indicating that there is interaction between the transgene and the genetic background. Moreover, when the non-tumor-bearing mos transgenic line is crossed to a different mouse background, the F1 offspring display the MEN 2 phenotype. These studies indicate that penetrance of the autosomal dominant mos transgenic phenotype is dependent on both integration site and background. C1 ST MARYS HOSP,SCH MED,LUDWIG INST CANC RES,LONDON W2 1PG,ENGLAND. SQUIBB INST CANC RES,DEPT MOLEC BIOL,PRINCETON,NJ 08543. USN HOSP,MED ONCOL BRANCH,NCI,BETHESDA,MD 20814. RP SCHULZ, N (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21701, USA. FU NCI NIH HHS [N01-CO-74101] NR 29 TC 35 Z9 35 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1992 VL 52 IS 2 BP 450 EP 455 PG 6 WC Oncology SC Oncology GA GZ693 UT WOS:A1992GZ69300033 PM 1345812 ER PT J AU WOODWORTH, CD LICHTI, U SIMPSON, S EVANS, CH DIPAOLO, JA AF WOODWORTH, CD LICHTI, U SIMPSON, S EVANS, CH DIPAOLO, JA TI LEUKOREGULIN AND GAMMA-INTERFERON INHIBIT HUMAN PAPILLOMAVIRUS TYPE-16 GENE-TRANSCRIPTION IN HUMAN PAPILLOMAVIRUS-IMMORTALIZED HUMAN CERVICAL CELLS SO CANCER RESEARCH LA English DT Article ID HUMAN FORESKIN KERATINOCYTES; CROSS-LINKED ENVELOPE; HUMAN EPIDERMAL-CELLS; NATURAL-KILLER; EPITHELIAL-CELLS; STRUCTURAL PROTEINS; CYTO-TOXICITY; UP-REGULATION; CARCINOMA; EXPRESSION AB The human papillomavirus (HPV) transforming genes E6 and E7 are retained and expressed in the majority of cervical cancers implying an important role for these proteins in maintenance of the malignant phenotype. Leukoregulin (LR) and recombinant gamma-interferon (r-IFN-gamma), lymphokines secreted by immune cells present in regressing HPV infections, inhibited transcription of E6/E7 RNAs in several human cervical epithelial cell lines immortalized by recombinant HPV-16, -18, and -33 DNAs. r-IFN-alpha was not effective. Reduction in E6/E7 RNA expression was accompanied by inhibition of cell proliferation coincident with an increase in epidermal transglutaminase activity, a marker of squamous differentiation. LR and r-IFN-gamma enhanced transcription of class 1 cell surface histocompatibility antigens (HLA) and r-IFN-gamma additionally induced HLA class 2 expression. HPV-immortalized cells developed partial resistance to the growth inhibitory effects of lymphokines after malignant transformation or extended propagation in culture. This is the first demonstration that LR and r-IFN-gamma selectively inhibit transcription of HPV-transforming genes and suggests a molecular mechanism by which these lymphokines participate in regression of premalignant cells. C1 NCI,DIV CANC ETIOL,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. RP WOODWORTH, CD (reprint author), NCI,DIV CANC ETIOL,BIOL LAB,BLDG 37,ROOM 2A19,BETHESDA,MD 20892, USA. NR 56 TC 75 Z9 78 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1992 VL 52 IS 2 BP 456 EP 463 PG 8 WC Oncology SC Oncology GA GZ693 UT WOS:A1992GZ69300034 PM 1345813 ER PT J AU GUTMAN, PD CAO, SX DAVE, HPG MITTELMAN, M SCHECHTER, AN AF GUTMAN, PD CAO, SX DAVE, HPG MITTELMAN, M SCHECHTER, AN TI BINDING OF ERYTHROID AND NONERYTHROID NUCLEAR PROTEINS TO THE SILENCER OF THE HUMAN EPSILON-GLOBIN-ENCODING GENE SO GENE LA English DT Article DE RECOMBINANT DNA; GENE EXPRESSION; TRANS-ACTING FACTORS; DNA-PROTEIN INTERACTION; DNASEI FOOTPRINTING; GEL RETARDATION ASSAY ID MAMMALIAN-CELLS; DNA; EXPRESSION; SEQUENCES; REGION AB To clarify the molecular mechanisms involved in the developmental control of hemoglobin-encoding genes we have been studying the expression of these genes in human cells in continuous culture. We have previously reported the presence of a transcriptional control element with the properties of a silencer extending from -392 to -177 bp relative to the cap site of the human epsilon-globin-encoding gene [Cao et al., Proc. Natl. Acad. Sci. USA 86 (1989) 5306-5309]. We also showed that this silencer has stronger inhibitory activity in HeLa cells, as compared to K562 human erythroleukemia cells. Using deletion mutants and cis-cloned synthetic oligodeoxyribonucleotides in transient expression assays, nucleotide sequences responsible for this effect have now been further delimited to 44 bp located from -294 to -251 bp. Gel electrophoresis mobility shift assays and DNaseI footprinting assays demonstrate that these negative regulatory sequences are recognized differently by proteins present in nuclear extracts obtained from HeLa and K562 cells. Two binding proteins are detected in K562 nuclear extracts, while only one is found in extracts from HeLa cells. Possible mechanisms by which these proteins may regulate transcription of the epsilon-globin-encoding gene in erythroid are discussed. C1 NIDDKO, CHEM BIOL LAB, BLDG 10, 9N-307, BETHESDA, MD 20892 USA. NR 24 TC 17 Z9 17 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 JAN 15 PY 1992 VL 110 IS 2 BP 197 EP 203 DI 10.1016/0378-1119(92)90648-9 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA HF713 UT WOS:A1992HF71300009 PM 1537556 ER PT J AU BRODSKY, RA STEIN, I AF BRODSKY, RA STEIN, I TI A MEDIASTINAL MASS IN A RED-FACED YOUNG WOMAN SO HOSPITAL PRACTICE LA English DT Article RP BRODSKY, RA (reprint author), NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 SN 8750-2836 J9 HOSP PRACT JI Hosp. Pract. PD JAN 15 PY 1992 VL 27 IS 1 BP 51 EP & PG 0 WC Medicine, General & Internal SC General & Internal Medicine GA HA835 UT WOS:A1992HA83500007 PM 1309830 ER PT J AU MAYES, LC GRANGER, RH BORNSTEIN, MH ZUCKERMAN, B AF MAYES, LC GRANGER, RH BORNSTEIN, MH ZUCKERMAN, B TI THE PROBLEM OF PRENATAL COCAINE EXPOSURE - A RUSH TO JUDGMENT SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID INFANT-DEATH-SYNDROME; MATERNAL COCAINE; PREGNANCY; DRUG; PREVALENCE; GROWTH; ABUSE; MARIJUANA; PATTERNS; INUTERO C1 NICHHD,BETHESDA,MD 20892. BOSTON UNIV,SCH MED,BOSTON,MA 02118. BOSTON CITY HOSP,BOSTON,MA 02118. RP MAYES, LC (reprint author), YALE CHILD STUDY CTR,230 S FRONTAGE RD,NEW HAVEN,CT 06510, USA. NR 41 TC 146 Z9 146 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 15 PY 1992 VL 267 IS 3 BP 406 EP 408 DI 10.1001/jama.267.3.406 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA GY437 UT WOS:A1992GY43700041 PM 1727966 ER PT J AU ANANT, JS ONG, OC XIE, H CLARKE, S OBRIEN, PJ FUNG, BKK AF ANANT, JS ONG, OC XIE, H CLARKE, S OBRIEN, PJ FUNG, BKK TI INVIVO DIFFERENTIAL PRENYLATION OF RETINAL CYCLIC-GMP PHOSPHODIESTERASE CATALYTIC SUBUNITS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID PHOTORECEPTOR CGMP PHOSPHODIESTERASE; MEMBRANE-BINDING DOMAIN; C-TERMINAL CYSTEINE; ROD OUTER SEGMENTS; G-PROTEIN; GAMMA-SUBUNIT; METHYL-ESTER; P21RAS; TRANSDUCIN; FARNESYL AB A number of phototransducing proteins in vertebrate photoreceptors contain a carboxyl terminal -CXXX motif (where C = cysteine and X = any amino acid), known to be a signal sequence for their post-translational prenylation and carboxyl methylation. To study the roles of these modifications in the visual excitation process, we have utilized an intravitreal injection method to radiolabel the prenylated proteins of rat retinas in vivo. We showed that two of the major prenylated polypeptides in the rod outer segments are the PDE(alpha) and PDE(beta) subunits of cyclic GMP phosphodiesterase (PDE). By chromatographic analyses of the amino acid constituents generated by exhaustive proteolysis of PDE(alpha) and PDE(beta) we further demonstrated that they are differentially prenylated by farnesylation and geranylgeranylation, respectively. While a number of proteins ending with the -CXXX sequence have already been reported to possess either a farnesyl or a geranylgeranyl group, PDE is the first enzyme shown to be modified by both types of prenyl groups. The prenyl modification of PDE most likely plays a major role in membrane attachment and in correctly positioning the PDE molecule for phototransduction. C1 UNIV CALIF LOS ANGELES,SCH MED,JULES STEIN EYE INST,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT CHEM & BIOCHEM,LOS ANGELES,CA 90024. NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. FU NEI NIH HHS [EY-05895]; NIGMS NIH HHS [GM-26060] NR 41 TC 135 Z9 135 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 15 PY 1992 VL 267 IS 2 BP 687 EP 690 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GY960 UT WOS:A1992GY96000003 PM 1309771 ER PT J AU LAMORTE, VJ GOLDSMITH, PK SPIEGEL, AM MEINKOTH, JL FERAMISCO, JR AF LAMORTE, VJ GOLDSMITH, PK SPIEGEL, AM MEINKOTH, JL FERAMISCO, JR TI INHIBITION OF DNA-SYNTHESIS IN LIVING CELLS BY MICROINJECTION OF GI2 ANTIBODIES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID PERTUSSIS TOXIN; FACTOR-II; PROTEIN; GROWTH; IDENTIFICATION; SERUM; ACID AB Heterotrimeric guanine nucleotide binding proteins function in the coupling of a diverse span of cell surface receptors to a variety of intracellular signaling pathways, some of which stimulate cellular proliferation. With the recent discovery that mutated forms of G proteins are present in specific tumors, there has been an increased interest in the determination of the role of specific subtypes of G proteins in the regulation of cellular growth. We have attempted to determine which subtypes of G proteins are directly involved in serum-stimulated DNA synthesis through microinjection of inhibitory antibodies into living cells. Inhibitory rabbit polyclonal antibodies directed against specific G(i) alpha-subunits were introduced into living Balb/c 3T3 fibroblasts by microinjection, and the effect upon serum-stimulated DNA synthesis was examined. Results of these experiments indicate that G(i2) plays a direct role in serum-stimulated DNA synthesis in living cells and suggest that G proteins may function in a variety of mitogenic signaling pathways initiated by serum growth factors. C1 UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,CTR CANC,LA JOLLA,CA 92093. NIDDKD,MOLEC PATHOPHYSIOL BRANCH,BETHESDA,MD 20892. RP LAMORTE, VJ (reprint author), UNIV CALIF SAN DIEGO,DEPT PHARMACOL,LA JOLLA,CA 92093, USA. NR 18 TC 59 Z9 59 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 15 PY 1992 VL 267 IS 2 BP 691 EP 694 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GY960 UT WOS:A1992GY96000004 PM 1730660 ER PT J AU ZHOU, D KORZEKWA, KR POULOS, T CHEN, S AF ZHOU, D KORZEKWA, KR POULOS, T CHEN, S TI A SITE-DIRECTED MUTAGENESIS STUDY OF HUMAN PLACENTAL AROMATASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BREAST; AROMATIZATION; MICROSOMES; PROTEINS AB Aromatase, a cytochrome P-450, catalyzes the formation of aromatic C18 estrogenic steroids from C19 androgens. Using the x-ray structure of cytochrome P-450 cam as the model, seven mutants of human aromatase were designed and expressed in Chinese hamster ovary cells by a stable expression method. They are His-128 --> Gln, His-128 --> Ala, Cys-299 --> Ala, Glu-302 Leu, Asp-309 --> Asn, Asp-309 --> Ala, and Ser-312 --> Cys. The presence of the aromatase mutants in the transfected Chinese hamster ovary cells were confirmed by immunoprecipitation analysis. The kinetic parameters of these mutants using [1-beta, 2-beta-H-3] androstenedione (or [1-beta-H-3]androstenedione), and [1-beta, 2-beta-H-3]testosterone as substrates were determined. In addition, inhibition profiles for these mutants with two aromatase inhibitors, 4-hydroxyandrostenedione and aminoglutethimide were obtained. Furthermore, the reactions catalyzed by these mutants were examined by evaluating the levels of the product estrone, and two intermediates, 19-hydroxyandrostenedione and 19-oxoandrostenedione by reverse phase high performance liquid chromatography using [7-H-3]androstenedione as the substrate. Our results indicate that among the positions we modified, Asp-309 appears to be very important for the enzyme catalysis. C1 CITY HOPE NATL MED CTR,BECKMAN RES INT,DIV IMMUNOL,DUARTE,CA 91010. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. UNIV CALIF IRVINE,DEPT MOLEC BIOL & BIOCHEM,IRVINE,CA 92717. FU NCI NIH HHS [CA 33572, CA 44735]; NIGMS NIH HHS [GM 33688] NR 19 TC 63 Z9 63 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 15 PY 1992 VL 267 IS 2 BP 762 EP 768 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GY960 UT WOS:A1992GY96000016 PM 1730667 ER PT J AU MURPHY, PM MCDERMOTT, D AF MURPHY, PM MCDERMOTT, D TI THE GUANINE NUCLEOTIDE-BINDING PROTEIN-GS ACTIVATES A NOVEL CALCIUM TRANSPORTER IN XENOPUS OOCYTES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TOXIN ADP-RIBOSYLATES; CHOLERA-TOXIN; HUMAN-NEUTROPHILS; ADENYLYL CYCLASE; BACTERIAL TOXINS; ION CHANNELS; RECEPTOR; ALPHA; CELLS; EXPRESSION AB Calcium influx is an important aspect of receptor-mediated signal transduction, yet limited information is available regarding the pathways of calcium influx into nonexcitable cells. We show that treatment of oocytes from Xenopus laevis with cholera toxin, a potent activator of the guanine nucleotide-binding protein G(s), specifically stimulates a sustained inward whole cell flux of calcium through a novel membrane transporter. The calcium is distributed into a mobilizable pool. The flux is voltage-independent and is completely and specifically blocked by microinjection of oocytes with an antiserum directed against G(s)alpha. The flux is not activated by treatment of the cells with forskolin or 8-bromo-cyclic adenosine monophosphate indicating that the effect of G(s)alpha on the transporter occurs independently of adenylylcyclase activation. Transporter activity is insensitive to benzyl amiloride, does not require a sodium gradient, and is rot stimulated by external calcium, indicating that it is not a sodium-calcium exchanger. The G(s)-activated flux is dramatically potentiated by lanthanum ion and other trivalent cations but not by any of six divalent cations that were tested; all other known calcium channels and exchangers are, in contrast, potently blocked by lanthanum. The divalent cation cadmium inhibited transporter activity in a concentration-dependent manner. This novel calcium transporter may be important for receptor-mediated calcium influx in the oocyte and perhaps other cell types. RP MURPHY, PM (reprint author), NIAID,HOST DEF LAB,BLDG 10,RM 11N113,BETHESDA,MD 20892, USA. OI McDermott, David/0000-0001-6978-0867 NR 39 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 15 PY 1992 VL 267 IS 2 BP 883 EP 888 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GY960 UT WOS:A1992GY96000033 PM 1309778 ER PT J AU TIPPER, J KAUFMAN, S AF TIPPER, J KAUFMAN, S TI PHENYLALANINE-INDUCED PHOSPHORYLATION AND ACTIVATION OF RAT HEPATIC PHENYLALANINE-HYDROXYLASE INVIVO SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SUBSTRATE ACTIVATION; PYRUVATE-KINASE; PROTEIN-KINASE; LIVER; GLUCAGON; 4-MONO-OXYGENASE; STIMULATION; INVITRO; ENZYME; ASSAY AB Rats were given intraperitoneal injections of 2 mCi of carrier-free P-32(i) and substances known to activate liver phenylalanine hydroxylase. After 30 min, these animals were anesthetized and their livers removed for analysis of enzyme activity, P-32(i) incorporation into immunoprecipitated phenylalanine hydroxylase and [gamma-P-32]ATP specific activity. Following glucagon treatment, rat liver phenylalanine hydroxylase activity was stimulated more than 6-fold when assayed in the presence of the natural cofactor, tetrahydrobiopterin (BH4). Glucagon injection also resulted in an incorporation of 0.41 mol of P-32(i)/mol of hydroxylase subunit (approximately 50,000 Da). In vivo stimulation of phenylalanine hydroxylase activity and P-32(i) incorporation by glucagon had been previously observed in this laboratory (Donlon, J., and Kaufman, S. (1978) J. Biol. Chem. 253, 6657-6659). However, we show for the first time in the present study that in vivo treatment with phenylalanine alone results in a 4-fold increase in the BH4-dependent activity of phenylalanine hydroxylase concomitant with a significant incorporation of phosphate into phenylalanine hydroxylase (0.51 mol of P-32(i)/mol of hydroxylase subunit). It is further demonstrated in vivo that the combined treatment with phenylalanine and glucagon results in a greater than 10-fold stimulation of BH4-dependent activity and the greatest level of P-32(i) incorporation (0.75 mol of P-32(i)/mol of hydroxylase subunit). Phenylalanine did not produce an elevation in plasma glucagon in these animals. A model is, thereby, proposed with respect to the ligand binding effects of phenylalanine on the state of phosphorylation and activation of phenylalanine hydroxylase. The significance of these regulatory roles are considered in light of the probable physiological environment of the enzyme. RP TIPPER, J (reprint author), NIMH,NEUROCHEM LAB,BETHESDA,MD 20892, USA. NR 35 TC 17 Z9 17 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 15 PY 1992 VL 267 IS 2 BP 889 EP 896 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GY960 UT WOS:A1992GY96000034 PM 1730677 ER PT J AU HIZI, A SHAHARABANY, M TAL, R HUGHES, SH AF HIZI, A SHAHARABANY, M TAL, R HUGHES, SH TI THE EFFECTS OF CYSTEINE MUTATIONS ON THE REVERSE TRANSCRIPTASES OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 AND TYPE-2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNASE-H; DNA-POLYMERASE; ESCHERICHIA-COLI; DOMAIN; MUTAGENESIS; RIBONUCLEASE; ORGANIZATION; EXPRESSION AB Chemical modification of HIV-1 and HIV-2 (human immunodeficiency virus, types 1 and 2) reverse transcriptases (RT) with three thiol reactive compounds selectively inhibits the RNase H function of the enzyme. HIV-1 RT has 2 cysteines (at positions 38 and 280); HIV-2 RT has 3 (38, 280, 445). Both of the cysteines in HIV-1 RT are in the polymerase domain. To investigate the role of the cysteines in the structure and function of the HIV RTs, we have converted each cysteine to serine and made combinations of the mutations. Since HIV-1 RT has alanine at position 445, we have also substituted alanine for serine at this position in HIV-2 RT. Neither of the single mutations in HIV-1 RT nor the double mutation mimics the effects of the chemical modification. The serine 280 mutation has little effect on either polymerase or RNase H; the serine 38 mutation affects both activities, as does the 38/280 double mutant. The 38 and 280 serine mutations in HIV-2 RT resemble the equivalent mutations in HIV-1 RT. Substitution of serine or alanine at position 445 (which lies in the RNase H domain) diminishes, but does not abolish, the RNase H activity of HIV-2 without affecting polymerase activity. The RNase H activity of a mutant HIV-1 RT with serine at position 280 is completely resistant to inactivation by the three thiol reactive compounds we tested, which demonstrates that cysteine 280 is the critical residue. We suggest that the reason the mutation (cysteine 280 to serine) does not mimic the chemical modification is because the chemical modification produces a greater change in the structure of the protein. We also suggest that position 280 lies at or near the important points of contact between the RNase H and polymerase domains, so that chemical modification of this position, which lies within the polymerase domain, distorts the RNase H domain. C1 TEL AVIV UNIV,SACKLER SCH MED,DEPT CELL BIOL & HISTOL,TEL AVIV,ISRAEL. RP HIZI, A (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,POB B,BLDG 539,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101]; NIAID NIH HHS [R01-AI27035] NR 22 TC 28 Z9 28 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 15 PY 1992 VL 267 IS 2 BP 1293 EP 1297 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GY960 UT WOS:A1992GY96000095 PM 1370463 ER PT J AU BRISTOL, LA FINCH, L ROMM, EV TAKACS, L AF BRISTOL, LA FINCH, L ROMM, EV TAKACS, L TI CHARACTERIZATION OF A NOVEL RAT THYMOCYTE COSTIMULATING ANTIGEN BY THE MONOCLONAL-ANTIBODY 1.3 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL-ACTIVATING PROTEIN; NEUTRAL ENDOPEPTIDASE; LYMPHOCYTIC-LEUKEMIA; EXPRESSION; DIFFERENTIATION; RECEPTORS; IMMATURE; MOLECULE; SELECTION; BINDING AB To define membrane-associated molecules that impart signals for the activation and expansion of double negative (DN) cells, mAb were raised against in vitro-cultured rat DN cells. One such mAb, 1.3, stimulated proliferation of DN cells along with submitogenic concentrations of PMA and IL-2 without affecting the mobilization of Ca2+. The 1.3 mAb precipitated a heterodimeric protein from DN cells and kidney (130/110 kDa). Although the tissue distribution and biochemical characteristics of the 1.3 determinant resemble the neutral aminopeptidase (AP-N) first described as the thymocyte activating molecule in the mouse, other data are contradictory; AP-N message was not detected in mRNA from 1.3 positive cells and the AP-N gene was absent in the genomic DNA from rat DN hybridomas expressing high levels of 1.3 Ag. In addition, the 1.3 mAb did not affect AP-N enzyme activity suggesting that 1.3 mAb does not function through this enzyme to transduce signals for proliferation. Thus, the 1.3 mAb defines a new and important thymocyte costimulating Ag. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21701. RP BRISTOL, LA (reprint author), NIAAA,ADAMHA,PHYSIOL & PHARMACOL STUDIES LAB,SPECIAL PROJECTS UNIT,ROCKVILLE,MD 20852, USA. FU NCI NIH HHS [N01-CO-74102] NR 40 TC 10 Z9 10 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 1992 VL 148 IS 2 BP 332 EP 338 PG 7 WC Immunology SC Immunology GA GZ965 UT WOS:A1992GZ96500004 PM 1345919 ER PT J AU WAHL, SM ALLEN, JB WELCH, GR WONG, HL AF WAHL, SM ALLEN, JB WELCH, GR WONG, HL TI TRANSFORMING GROWTH-FACTOR-BETA IN SYNOVIAL-FLUIDS MODULATES FC-GAMMA-RIII (CD16) EXPRESSION ON MONONUCLEAR PHAGOCYTES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; CULTURED HUMAN-MONOCYTES; PERIPHERAL-BLOOD; INFLAMMATORY ARTHRITIS; RHEUMATOID-ARTHRITIS; IMMUNOGLOBULIN-G; RECEPTORS; IGG; INTERFERON; DIFFERENTIATION AB Mononuclear phagocytes in the synovium of patients with arthritis, in contrast to blood monocytes, were found to express a third receptor for the constant region of Ig (Fc-gamma-RIII), in addition to Fc-gamma-RI and Fc-gamma-RII. Previously identified on mature mononuclear phagocytes or phagocytes exposed to transforming growth factor-beta (TGF-beta) in vitro, this study documents the presence of Fc-gamma-RIII (CD16) expressing cells at an inflammatory site. Furthermore, the presence of CD16 on the majority of the LeuM3 (CD14) positive synovial monocytic cells could be mimicked by exposing blood monocytes to synovial fluids from patients with rheumatoid arthritis (17 of 19) and synovial fluids from patients with osteoarthritis (4 of 4). In additional studies, the soluble factor in inflammatory synovial fluids responsible for regulating CD16 expression was found to be consistent with the presence of TGF-beta. Inhibition of the activity in synovial fluids with a neutralizing antibody to TGF-beta confirmed a role for this peptide in synovial phagocytic cell CD16 expression. Moreover, signal transduction through CD16 on synovial phagocytes resulted in augmented extracellular release of superoxide anion that may contribute to tissue damage and other inflammatory sequelae. Identification of TGF-beta and its association with up-regulation of CD16 at sites of chronic inflammation may provide insight into the destructive lesions associated with inflammatory arthropathies. RP WAHL, SM (reprint author), NIDR, IMMUNOL LAB, CELLULAR IMMUNOL SECT, BLDG 30, ROOM 326, BETHESDA, MD 20892 USA. NR 51 TC 41 Z9 41 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 1992 VL 148 IS 2 BP 485 EP 490 PG 6 WC Immunology SC Immunology GA GZ965 UT WOS:A1992GZ96500026 PM 1309559 ER PT J AU LAVOIE, TB DROHAN, WN SMITHGILL, SJ AF LAVOIE, TB DROHAN, WN SMITHGILL, SJ TI EXPERIMENTAL-ANALYSIS BY SITE-DIRECTED MUTAGENESIS OF SOMATIC MUTATION EFFECTS ON AFFINITY AND FINE SPECIFICITY IN ANTIBODIES SPECIFIC FOR LYSOZYME SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHAIN JUNCTIONAL DIVERSITY; 3-DIMENSIONAL STRUCTURE; MONOCLONAL-ANTIBODIES; VARIABLE-REGION; ANTIGEN-BINDING; HYPERVARIABLE REGIONS; AVIAN LYSOZYME; LIGHT-CHAINS; H-CHAIN; COMPLEX AB To experimentally examine the functional roles of somatically derived structural variation in the lysozyme-binding mAb HyHEL-10, we have introduced three different point mutations and one insertion at two different sites in HyHEL-10 by site-directed mutagenesis and expression of the mutant antibodies. Mutation of Asp --> Ala at position 101 of the H chain retums a somatically mutated residue to its germline sequence for HyHEL-10, and reduces affinity for chicken lysozyme by approximately 9000-fold. Lengthening the third H chain hypervariable region by two amino acids reduces affinity by about 2000-fold. Two mutations, Asp --> Thr at position 101 in the H chain and Lys --> Thr at position 49 in the L chain, model somatic differences found in another structurally related but functionally distinguishable mAb and minimally decrease affinity for chicken lysozyme. The H chain mutation Asp101V(VH) --> Thr has little effect on affinity for other avian lysozymes but does alter relative fine specificity for these lysozymes. The L chain mutation Lys49(Vk) --> Thr increases affinity for duck lysozyme by approximately fivefold. Neither of the positions mutated, 101 in the H chain nor 49 in the L chain, nor the residues near the insertion contact lysozyme in the x-ray structure of the HyHEL-10 F(ab)-HEL complex. The results suggest that these mutations, which model observed somatic mutations, produce functional variation by indirect or long-range effects. C1 NCI,GENET LAB,BLDG 37,ROOM 2B10,BETHESDA,MD 20892. UNIV MARYLAND,DEPT ZOOL,COLLEGE PK,MD 20742. AMER RED CROSS,PLASMA DERIVAT LAB,ROCKVILLE,MD 20855. NR 65 TC 135 Z9 136 U1 1 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 1992 VL 148 IS 2 BP 503 EP 513 PG 11 WC Immunology SC Immunology GA GZ965 UT WOS:A1992GZ96500029 PM 1729369 ER PT J AU HAMAWY, MM OLIVER, C SIRAGANIAN, RP AF HAMAWY, MM OLIVER, C SIRAGANIAN, RP TI INHIBITION OF IGE BINDING TO RBL-2H3 CELLS BY A MONOCLONAL-ANTIBODY (BD6) TO A SURFACE PROTEIN OTHER THAN THE HIGH-AFFINITY IGE RECEPTOR SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BASOPHILIC LEUKEMIA-CELLS; HISTAMINE-RELEASE; SEROTONIN RELEASE; IMMUNOGLOBULIN-E; MAST-CELLS; ASSOCIATION; HYBRIDOMAS; MEMBRANE; COMPLEX; CD8 AB A mAb was isolated (mAb BD6) that recognized a surface glycoprotein on rat basophilic leukemia cells (RBL-2H3). The antibody bound to 2 x 10(6) molecules/cell and specifically blocked IgE binding (50% inhibition with 3.48 +/- 0.51-mu-g/ml; mean +/- SEM), although neither IgE nor anti-high affinity IgE receptor (anti-Fc-epsilon-RI) mAb blocked mAb BD6 binding to the cells. mAb BD6 did not affect the rate of dissociation of cell-bound IgE, nor did it induce or inhibit the internalization of IgE. mAb BD6 did not release histamine. However, it did cause rapid spreading of the cells. By 1 h the cells had retracted to a spherical shape with their surface covered with membranous spikes, and they could easily be detached from the tissue culture plate. These changes differed from those observed after Fc-epsilon-RI activation. mAb BD6 immunoprecipitated a complex of two proteins, 38 to 50 kDa and 135 kDa from I-125-surface labeled rat basophilic leukemia cells that are not subunits of Fc-epsilon-RI. Chemical cross-linking studies showed that these molecules are associated on the cell surface. By immunoblotting, mAb BD6 reacted with a 40-kDa protein. Therefore, mAb BD6 binds to a surface protein that is close to the Fc-epsilon-RI and sterically inhibits I-125-IgE binding. C1 NIDR,IMMUNOL LAB,CLIN IMMUNOL SECT,BLDG 10,ROOM 1N106,BETHESDA,MD 20892. NR 30 TC 14 Z9 14 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 1992 VL 148 IS 2 BP 524 EP 531 PG 8 WC Immunology SC Immunology GA GZ965 UT WOS:A1992GZ96500031 PM 1370314 ER PT J AU BERGSAGEL, PL VICTORKOBRIN, C TIMBLIN, CR TREPEL, J KUEHL, WM AF BERGSAGEL, PL VICTORKOBRIN, C TIMBLIN, CR TREPEL, J KUEHL, WM TI A MURINE CDNA ENCODES A PAN-EPITHELIAL GLYCOPROTEIN THAT IS ALSO EXPRESSED ON PLASMA-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN LYMPHOID-CELLS; MONOCLONAL-ANTIBODY; MOLECULAR-CLONING; PROTO-ONCOGENE; LUNG-CANCER; LINES; ANTIGEN; IDENTIFICATION; SEQUENCE; MYELOMA AB Using a subtractive cDNA approach, we have identified a number of genes expressed in murine plasmacytomas, but not B or pre-B lymphomas. One of these genes, 289A, expresses a 1.8-kb microsomally localized mRNA that encodes a 314-amino-acid protein containing a signal sequence and a hydrophobic transmembrane domain. Sequence comparison suggests that the predicted protein is the murine homologue of a human cell surface pan-epithelial glycoprotein known variously as EGP, GA733-2, KSA, and KS1/4, recognized by mAb HEA125, GA733, KS1/4,CO17-1A,M74, and 323/A3.The 289A mRNA is highly expressed in normal murine tissues containing epithelial cells, and at a low level in plasma cells induced by LPS stimulation of spleen B lymphocytes. It is expressed in 15 of 16 plasmacytomas, but at a much lower level, if at all, in pre-B or B lymphomas. In human B cell lines, 289A detects a 1.5-kb mRNA in the myeloma cell line 8226, but not in Burkitt's lymphoma or lymphoblastoid cell lines. Subsequent FACS analysis of human cell lines with the mAb GA733 and KS1/4 demonstrated concordant expression of the mRNA and the protein. We conclude that 289A is the murine homologue of EGP, GA733-2, KSA, and KS1/4 Ag. Although its expression was previously thought to be restricted to epithelial cells, it is also expressed in plasma cells and is a B lymphocyte differentiation Ag. Because of the multiplicity of names, we propose calling the human gene hEGP314, and the murine gene mEGP314. C1 USN,NCI,MED ONCOL BRANCH,BLDG 8,ROOM 5101,BETHESDA,MD 20889. NCI,MED BRANCH,BETHESDA,MD 20889. NR 43 TC 69 Z9 70 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 1992 VL 148 IS 2 BP 590 EP 596 PG 7 WC Immunology SC Immunology GA GZ965 UT WOS:A1992GZ96500040 PM 1729376 ER PT J AU KAWAKAMI, Y ZAKUT, R TOPALIAN, SL STOTTER, H ROSENBERG, SA AF KAWAKAMI, Y ZAKUT, R TOPALIAN, SL STOTTER, H ROSENBERG, SA TI SHARED HUMAN-MELANOMA ANTIGENS - RECOGNITION BY TUMOR-INFILTRATING LYMPHOCYTES IN HLA-A2.1-TRANSFECTED MELANOMAS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN METASTATIC MELANOMAS; T-CELL RECOGNITION; AUTOLOGOUS TUMOR; SELF DETERMINANTS; SPECIFICITY; INTERLEUKIN-2; IMMUNOTHERAPY; RECEPTOR; CLONES; HLA-A2 AB Three predominantly CD8+ CTL lines, TIL 501, TIL 620, and TIL 660, were generated from three HLA-A2+ melanoma patients by culturing tumor-infiltrating lymphocytes in 1000 U/ml IL-2. These tumor-infiltrating lymphocytes lysed 12 of 18 HLA-A2+ autologous and allogeneic melanomas, but none of 20 HLA-A2-negative melanomas. They also did not lyse the MHC class I negative lymphoma-leukemia cell lines, Daudi, K562, or HLA-A2+ non-melanoma cell lines including PHA or Con A-induced lymphoblast, fibroblast, EBV-transformed B cell, Burkitt's B cell lymphoma, and colon cancer cell lines. Autologous and allogeneic melanoma lysis was inhibited by anti-CD3, by anti-MHC class I, and by anti-HLA-A2 mAb, indicating recognition of shared tumor Ag among melanoma cell lines in a TCR-dependent, HLA-A2-restricted manner. Six HLA-A2-negative melanoma cell lines obtained from five HLA-A2-negative patients were co-transfected with the HLA-A2.1 gene and pSV2neo. All 17 cloned transfectants expressing cell surface HLA-A2 molecules, but none of 12 transfectants lacking HLA-A2 expression, were lysed by these three HLA-A2-restricted, melanoma-specific CTL. Lysis of the HLA-A2+ transfectants was inhibited by anti-CD3, by anti-MHC class I, and by anti-HLA-A2 mAb, indicating recognition of shared tumor Ag on transfectants in a TCR-dependent, HLA-A2-restricted manner. These results identify the HLA-A2.1 molecule as an Ag-presenting molecule for melanoma Ag. They also suggest that common melanoma Ag are expressed among melanoma patients regardless of HLA type. These findings have implications for the development of melanoma vaccines that would induce antitumor T cell responses. RP KAWAKAMI, Y (reprint author), NCI,DIV CANC TREATMENT,SURG BRANCH,BLDG 10,ROOM 2B08,BETHESDA,MD 20892, USA. RI Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 NR 35 TC 173 Z9 173 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 1992 VL 148 IS 2 BP 638 EP 643 PG 6 WC Immunology SC Immunology GA GZ965 UT WOS:A1992GZ96500047 PM 1729379 ER PT J AU MIYAZAWA, M NISHIO, J WEHRLY, K CHESEBRO, B AF MIYAZAWA, M NISHIO, J WEHRLY, K CHESEBRO, B TI INFLUENCE OF MHC GENES ON SPONTANEOUS-RECOVERY FROM FRIEND RETROVIRUS-INDUCED LEUKEMIA SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; IMMUNE-RESPONSE GENES; FOCUS-FORMING VIRUS; MURINE LEUKEMIA; T-CELL; H-2; ANTIGENS; ERYTHROLEUKEMIA; IDENTIFICATION; ANTIBODIES AB Genes influencing the rate of spontaneous recovery from erythroleukemia induced by a low dose of Friend virus complex were located in the right and left portions of the mouse MHC. The right side gene was most likely the previously described Rfv-1 in the H-2D region. Using the B6.C-H-2bm12 mutant mice, the left side gene was mapped to the A-beta class II locus. The A-beta(b) was a resistant allele and A-beta(k) and A-beta(bm12) were susceptible alleles. Genes at this class II locus controlled the responsiveness of Th cells to envelope glycoprotein of Friend murine leukemia helper virus and affected the class switching of virus-neutralizing antibodies from Igm to IgG in FV-infected mice. C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,903 S 4TH ST,HAMILTON,MT 59840. NR 36 TC 27 Z9 28 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 1992 VL 148 IS 2 BP 644 EP 647 PG 4 WC Immunology SC Immunology GA GZ965 UT WOS:A1992GZ96500048 PM 1729380 ER PT J AU BILSKI, P CHIGNELL, CF SZYCHLINSKI, J BORKOWSKI, A OLEKSY, E RESZKA, K AF BILSKI, P CHIGNELL, CF SZYCHLINSKI, J BORKOWSKI, A OLEKSY, E RESZKA, K TI PHOTOOXIDATION OF ORGANIC AND INORGANIC SUBSTRATES DURING UV PHOTOLYSIS OF NITRITE ANION IN AQUEOUS-SOLUTION SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID ELECTRON-SPIN RESONANCE; NITROGEN-DIOXIDE; PULSE-RADIOLYSIS; HYDROGEN-PEROXIDE; QUANTUM YIELDS; FREE-RADICALS; SODIUM-AZIDE; OH RADICALS; WATER; KINETICS AB The UV photolysis (360 nm) of nitrite anion has been investigated in aqueous solution in the presence of organic and inorganic substrates: alcohols, 1,4-dioxane, sodium ascorbate, Me2CO, Me2SO, HCOONa, NaSCN, NaN3, Na2S, and Na2SO3. The hydroxyl radical, the primary photodissociation product of NO2-, was observed by electron spin resonance (EPR) using the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO). With nitromethane (NM) in alkaline solution as a spin trapping agent, we observed NO2. which is a product of HO. self-scavenging by nitrite. In the presence of organic/inorganic substrates, the HO. radical gives rise to secondary radicals which we trapped and identified as DMPO or NM adducts; the respective EPR spectra are presented. Secondary carbon radicals react with oxygen in solution increasing the yield of oxygen consumption 10-1000 times over the control level. The quantum yield of O2 consumption increases with increasing molar ratio of the substrate/NO2-, usually following the plot of oxygen solubility in solution. Besides HO. radicals, nitrogen oxides and inorganic nitrogen peroxides may also contribute to oxidation by nitrite. We also detected weak singlet oxygen phosphorescence during UV irradiation of NO2- in deuterium oxide. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. UNIV GDANSK,INST CHEM,PL-80952 GDANSK,POLAND. NR 58 TC 51 Z9 52 U1 3 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JAN 15 PY 1992 VL 114 IS 2 BP 549 EP 556 DI 10.1021/ja00028a023 PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA GZ441 UT WOS:A1992GZ44100023 ER PT J AU GIBBS, CJ BOLIS, CL ASHER, DM BRADLEY, R FITE, RW JOHNSON, RT MAHY, BWJ MCKHANN, GM AF GIBBS, CJ BOLIS, CL ASHER, DM BRADLEY, R FITE, RW JOHNSON, RT MAHY, BWJ MCKHANN, GM TI RECOMMENDATIONS OF THE INTERNATIONAL-ROUND-TABLE-WORKSHOP ON BOVINE SPONGIFORM ENCEPHALOPATHY SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Editorial Material C1 ASSOC INT RECH ENSEIGNEMENT NEUROSCI,CH-1204 GENEVA,SWITZERLAND. MAFF,CENT VET LAB,WEYBRIDGE KT15 3NB,SURREY,ENGLAND. USDA,ANIM & PLANT HLTH INSPECT SERV,HYATTSVILLE,MD 20782. JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD 21205. CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,ATLANTA,GA 30333. RP GIBBS, CJ (reprint author), NIH,BLDG 36,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 11 TC 4 Z9 4 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD JAN 15 PY 1992 VL 200 IS 2 BP 164 EP 167 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA GZ407 UT WOS:A1992GZ40700003 PM 1348501 ER PT J AU TABOR, E KOBAYASHI, K AF TABOR, E KOBAYASHI, K TI HEPATITIS-C VIRUS, A CAUSATIVE INFECTIOUS AGENT OF NON-A, NON-B HEPATITIS - PREVALENCE AND STRUCTURE - SUMMARY OF A CONFERENCE ON HEPATITIS-C VIRUS AS A CAUSE OF HEPATOCELLULAR-CARCINOMA SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material C1 KANAZAWA UNIV,DEPT INTERNAL MED 1,KANAZAWA,ISHIKAWA 920,JAPAN. RP TABOR, E (reprint author), NCI,DIV CANC ETIOL,BIOL CARCINOGENESIS PROGRAM,BETHESDA,MD 20892, USA. NR 0 TC 26 Z9 26 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 15 PY 1992 VL 84 IS 2 BP 86 EP 90 DI 10.1093/jnci/84.2.86 PG 5 WC Oncology SC Oncology GA HG725 UT WOS:A1992HG72500008 PM 1346540 ER PT J AU LONGO, DL AF LONGO, DL TI EFFECT OF DIETARY-FAT ON HUMAN BREAST-CANCER GROWTH AND LUNG METASTASIS IN NUDE-MICE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter RP LONGO, DL (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,FREDERICK,MD 21701, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 15 PY 1992 VL 84 IS 2 BP 127 EP 127 DI 10.1093/jnci/84.2.127 PG 1 WC Oncology SC Oncology GA HG725 UT WOS:A1992HG72500015 PM 1735878 ER PT J AU LEE, JS HAVLIN, S STANLEY, HE AF LEE, JS HAVLIN, S STANLEY, HE TI ANALYTIC SOLUTION OF THE GROWTH-SITE PROBABILITY-DISTRIBUTION FOR STRUCTURAL MODELS OF DIFFUSION-LIMITED AGGREGATION SO PHYSICAL REVIEW A LA English DT Article ID MULTIFRACTAL BEHAVIOR; BREAKDOWN; SURFACES; FRACTALS AB We present an analytic solution of the growth-site probability distribution for a family of hierarchical models for the structure of diffusion-limited aggregation (DLA) clusters. These models are characterized by self-similar voids that are delineated by narrow channels. The growth-site probability distributions for all the models are shown to have the same form, n(alpha,M) approximately exp{-(A/lnM)[alpha-alpha-0(M)]2}, where n(alpha,M)d-alpha is the number of growth sites with alpha < -lnp(i)/lnM < alpha + d-alpha, p(i) is the growth probability at site i, M is the cluster mass, alpha-0(M) = B lnM, and A,B are constants. We find the same form of the distribution for all members of the family of models, suggesting the possibility that it is a consequence of the channels and self-similar voids, and is independent of other details of the model. Our result is in accord with the recent calculations for DLA clusters by Schwarzer et al. [Phys. Rev. A 43, 1134 (1991)]. C1 BOSTON UNIV,CTR POLYMER STUDIES,BOSTON,MA 02215. BOSTON UNIV,DEPT PHYS,BOSTON,MA 02215. NIH,DCRT,PHYS SCI LAB,BETHESDA,MD 20892. RI Lee, Jysoo/N-8473-2015 NR 43 TC 7 Z9 7 U1 0 U2 0 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1050-2947 J9 PHYS REV A JI Phys. Rev. A PD JAN 15 PY 1992 VL 45 IS 2 BP 1035 EP 1043 DI 10.1103/PhysRevA.45.1035 PG 9 WC Optics; Physics, Atomic, Molecular & Chemical SC Optics; Physics GA HB019 UT WOS:A1992HB01900055 ER PT J AU MOSINGER, B TILLMANN, U WESTPHAL, H TREMBLAY, ML AF MOSINGER, B TILLMANN, U WESTPHAL, H TREMBLAY, ML TI CLONING AND CHARACTERIZATION OF A MOUSE CDNA-ENCODING A CYTOPLASMIC PROTEIN-TYROSINE-PHOSPHATASE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TYROSINE PHOSPHORYLATION; MOUSE EMBRYO; HUMAN T-CELL PROTEIN-TYROSINE-PHOSPHATASE ID SIGNAL TRANSDUCTION; KINASE-ACTIVITY; FAMILY; GENE; DEPHOSPHORYLATION; ACTIVATION AB A mouse cDNA encoding a non-receptor-type phosphotyrosine phosphatase (PTP; EC 3.1.3.48) has been isolated. The 1570-base-pair cDNA contains a single open reading frame that predicts a 382-amino acid protein with M, 44,640. The nucleic acid and amino acid sequences are homologous to those of a previously described human T-cell PTP [Cool, D. E., Tonks, N. K., Charbonneau, H., Walsh, K. A., Fischer, E. H. & Krebs, E. G. (1989) Proc. Natl. Acad. Sci. USA 86, 5257-5261]; however, the mouse and human 3' sequences diverge and predict markedly different protein carboxyl termini. The mouse PTP gene is expressed as a 1.9-kilobase message in several stages of murine embryonic development and in a variety of adult tissues. An additional 1.3-kilobase message was found to be expressed specifically in testes. Finally, we report the isolation of a human T-cell PTP cDNA containing a 3' end sequence homologous to the mouse PTP. RP MOSINGER, B (reprint author), NICHHD,MAMMALIAN GENES & DEV LAB,BLDG 6,BETHESDA,MD 20892, USA. NR 35 TC 85 Z9 87 U1 0 U2 0 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 15 PY 1992 VL 89 IS 2 BP 499 EP 503 DI 10.1073/pnas.89.2.499 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GZ696 UT WOS:A1992GZ69600011 PM 1731319 ER PT J AU FELDER, CC POULTER, MO WESS, J AF FELDER, CC POULTER, MO WESS, J TI MUSCARINIC RECEPTOR-OPERATED CA2+ INFLUX IN TRANSFECTED FIBROBLAST CELLS IS INDEPENDENT OF INOSITOL PHOSPHATES AND RELEASE OF INTRACELLULAR CA2+ SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CALCIUM CHANNELS; RECEPTOR CHIMERAS; PHORBOL ESTER; ARACHIDONIC ACID ID A9 L-CELLS; CA-2+ MOBILIZATION; ARACHIDONIC-ACID; ION CHANNELS; 1,4,5-TRISPHOSPHATE; IDENTIFICATION; STIMULATION; DELINEATION; REGION; GENES AB Receptor-mediated changes in cytoplasmic calcium concentrations occur either through release from intracellular calcium stores or hy the opening of channels in the plasma membrane, allowing influx of calcium from the extracellular fluid. Carbachol, a muscarinic receptor agonist, stimulated both calcium influx and inositol 1,4,5-trisphosphate (InsP3)-mediated intracellular calcium release in A9 fibroblast cells expressing a m3 muscarinic receptor clone. The calcium influx persisted even after pretreatment of cells with phorbol 12-myristate 13-acetate, which completely prevented the rise in inositol phosphates and intracellular calcium levels. The calcium influx was blocked by divalent cations but was not affected by inhibitors of voltage-dependent calcium channels or high potassium depolarization, indicating the presence of a receptor-operated and voltage-insensitive calcium channel in these cells. Calcium influx was not stimulated by the addition of cAMP analogs or arachidonic acid. To examine the possible involvement of G proteins in m3 receptor-activated calcium influx, two chimeric m2 and m3 muscarinic receptors were expressed in A9 cells in which the third cytoplasmic loop (the primary structural determinant in G protein coupling selectivity of muscarinic receptors) had been exchanged between the m2 receptor, which has no effect on calcium influx, and the m3 receptor. Calcium influx was found to be associated with a structural component of the m3 muscarinic receptor other than the third cytoplasmic loop. C1 NINCDS,MOLEC BIOL LAB,BETHESDA,MD 20892. NINCDS,NEUROPHYSIOL LAB,BETHESDA,MD 20892. RP FELDER, CC (reprint author), NIMH,CELL BIOL LAB,BLDG 36,ROOM 3A-15,BETHESDA,MD 20892, USA. RI Poulter, Michael/K-3909-2013 OI Poulter, Michael/0000-0001-7469-8462 NR 27 TC 96 Z9 96 U1 0 U2 0 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 15 PY 1992 VL 89 IS 2 BP 509 EP 513 DI 10.1073/pnas.89.2.509 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GZ696 UT WOS:A1992GZ69600013 PM 1731321 ER PT J AU MURAMATSU, T GIRI, PR HIGUCHI, S KINCAID, RL AF MURAMATSU, T GIRI, PR HIGUCHI, S KINCAID, RL TI MOLECULAR-CLONING OF A CALMODULIN-DEPENDENT PHOSPHATASE FROM MURINE TESTIS - IDENTIFICATION OF A DEVELOPMENTALLY EXPRESSED NONNEURAL ISOENZYME SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CALCINEURIN; SPERMATOGENESIS; PHOSPHOPROTEINS; GENE DIVERSITY ID PROTEIN PHOSPHATASE; CALCINEURIN-A; CATALYTIC SUBUNIT; MOUSE-BRAIN; DOMAIN; LOCALIZATION; ISOZYMES; NEURONS AB A unique isoform of the catalytic subunit of calmodulin-dependent protein phosphatase (CaM-PrP) was cloned from a murine testis library. The cDNA sequence of 1964 base pairs contained an open reading frame encoding a protein of 513 amino acids (M(r) almost-equal-to 58,706), the predicted isoelectric point of which (pI 7.1) was much more basic than those of brain isoforms (pI 5.6-5.8). The deduced amino acid sequence was 77-81 % identical to two other murine CaM-PrP genes and displayed a distinct Southern blot hybridization pattern, indicating that it was derived from a separate gene (type 3). High amounts of a 2800-nucleotide mRNA transcript were observed in testis, whereas mRNA species were not detectable in brain; thus, it seems likely that this CaM-PrP represents a nonneural isoenzyme. Measurements of CaM-PrP mRNA during testicular development showed a dramatic increase in expression during weeks 4-6, correlating with the later stages of spermatogenesis. These data suggest that this phosphatase isoform may be involved in germ-cell function and are consistent with the report of a flagellum-associated form of CaM-PrP that may regulate sperm motility [Tash, J. S., Krinks, M., Patel, J., Means, R. L., Klee, C. B. & Means, A. R. (1988) J. Cell Biol. 106, 1625-1633]. RP NIAAA, MOLEC & CELLULAR NEUROBIOL LAB, IMMUNOL SECT, ROCKVILLE, MD 20852 USA. NR 32 TC 85 Z9 87 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 15 PY 1992 VL 89 IS 2 BP 529 EP 533 DI 10.1073/pnas.89.2.529 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GZ696 UT WOS:A1992GZ69600017 PM 1309945 ER PT J AU TSAREV, SA EMERSON, SU REYES, GR TSAREVA, TS LEGTERS, LJ MALIK, IA IQBAL, M PURCELL, RH AF TSAREV, SA EMERSON, SU REYES, GR TSAREVA, TS LEGTERS, LJ MALIK, IA IQBAL, M PURCELL, RH TI CHARACTERIZATION OF A PROTOTYPE STRAIN OF HEPATITIS-E VIRUS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ANTI-HEPATITIS-E VIRUS ANTIBODIES; PCR; GENOME SEQUENCE COMPARISON ID NON-B-HEPATITIS; TRANSMITTED NON-A; PUTATIVE CAUSATIVE VIRUS; CYNOMOLGUS MACAQUES; MACACA-MULATTA; TRANSMISSION; POLYPEPTIDES; PARTICLES; SEQUENCE; RECOVERY AB A strain of hepatitis E virus (SAR-55) implicated in an epidemic of enterically transmitted non-A, non-B hepatitis, now called hepatitis E, was characterized extensively. Six cynomolgus monkeys (Macaca fascicularis) were infected with a strain of hepatitis E virus from Pakistan. Reverse transcription-polymerase chain reaction was used to determine the pattern of virus shedding in feces, bile, and serum relative to hepatitis and induction of specific antibodies. Virtually the entire genome of SAR-55 (7195 nucleotides) was sequenced. Comparison of the sequence of SAR-55 with that of a Burmese strain revealed a high level of homology except for one region encoding 100 amino acids of a putative nonstructural polyprotein. Identification of this region as hypervariable was obtained by partial sequencing of a third isolate of hepatitis E virus from Kirgizia. C1 MM SHEMYAKIN BIOORGAN CHEM INST,MOSCOW 117871,USSR. ARMY MED COLL,PAKISTAN US LAB SEROEPIDEMIOL,RALWALPIND,PAKISTAN. GENELABS INC,DEPT MOLEC VIROL,REDWOOD CITY,CA 94063. UNIFORMED SERV UNIV HLTH SCI,DEPT PREVENT MED & BIOMETR,BETHESDA,MD 20814. RP TSAREV, SA (reprint author), NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BLDG 7,ROOM 200,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [N01-AI-05069] NR 30 TC 208 Z9 214 U1 0 U2 7 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 15 PY 1992 VL 89 IS 2 BP 559 EP 563 DI 10.1073/pnas.89.2.559 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GZ696 UT WOS:A1992GZ69600023 PM 1731327 ER PT J AU ISAACS, SN KOTWAL, GJ MOSS, B AF ISAACS, SN KOTWAL, GJ MOSS, B TI VACCINIA VIRUS COMPLEMENT-CONTROL PROTEIN PREVENTS ANTIBODY-DEPENDENT COMPLEMENT-ENHANCED NEUTRALIZATION OF INFECTIVITY AND CONTRIBUTES TO VIRULENCE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE COMPLEMENT BINDING PROTEIN; VIRUS NEUTRALIZATION; ATTENUATION; IMMUNITY ID 3RD COMPONENT; ACTIVATION; DEFICIENCY; RECEPTOR; SYSTEM AB The role of a viral gene product in evasion of the host immune response was investigated. The antibody-dependent complement-enhanced neutralization of vaccinia virus infectivity was prevented by the culture medium from vaccinia virus-infected cells. The vaccinia virus complement-control protein (VCP) was identified as the secreted product of vaccinia virus gene C21L and has homology to a group of eukaryotic genes encoding regulators of complement activation. Thus, the culture medium from cells infected with a C21L deletion mutant was VCP deficient and had little or no effect on antibody-dependent complement-enhanced neutralization. In addition, the anticomplement effect was associated with the C21L-encoded protein partially purified from the medium of cells infected with wild-type virus. Antibody-dependent, complement-enhanced neutralization of vaccinia virus occurred with a complement source that was deficient in the classical pathway complement component C4 and required the alternative pathway complement factor B. Furthermore, the presence of VCP abrogated the complement-enhanced neutralization in C4-deficient serum. Together with previous hemolysis data, the present result suggests that VCP can inhibit both the classical and alternative pathways of complement activation. Skin lesions caused by the C21L deletion mutant were smaller than those caused by wild-type virus, demonstrating an important role for VCP in virulence. The C21L deletion mutant also was attenuated in C4-deficient guinea pigs, consistent with in vitro studies. Vaccinia virus appears to have acquired the ability to regulate the complement cascade for the purpose of evading the host immune response. RP ISAACS, SN (reprint author), NIAID,VIRAL DIS LAB,BETHESDA,MD 20892, USA. NR 26 TC 180 Z9 182 U1 0 U2 1 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 15 PY 1992 VL 89 IS 2 BP 628 EP 632 DI 10.1073/pnas.89.2.628 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GZ696 UT WOS:A1992GZ69600037 PM 1731333 ER PT J AU DIXON, DO SIMON, R AF DIXON, DO SIMON, R TI BAYESIAN SUBSET ANALYSIS IN A COLORECTAL-CANCER CLINICAL-TRIAL SO STATISTICS IN MEDICINE LA English DT Article AB Subset analysis is the examination of treatment comparisons within groups of patients with restricted levels of patient characteristics. Such analyses are vulnerable to multiplicity effects. We examine the problem in the context of a proportional hazards model with terms for treatment, each of several dichotomous covariates representing the patient characteristics of interest, and treatment-by-covariate interaction effects. Parametrically, a subset-specific treatment effect is equal to the treatment effect term plus a linear combination of the interaction terms. We present Bayesian point and interval estimates under the assumption that the interaction terms are exchangeable and the prior distributions for the other regression parameters are locally uniform. This produces a shrinking of the estimated interaction effects towards zero, thereby discounting them and dealing in a natural way with multiplicity. We illustrate the method using results of a recent North Central Cancer Treatment Group/Mayo Clinic study in advanced colorectal cancer. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT BIOMATH,HOUSTON,TX 77030. NCI,DIV CANC TREATMENT,BIOMETR RES BRANCH,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892. FU NCI NIH HHS [CA-11430] NR 4 TC 32 Z9 32 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 15 PY 1992 VL 11 IS 1 BP 13 EP 22 PG 10 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA HC732 UT WOS:A1992HC73200003 PM 1557569 ER PT J AU FREEDMAN, LS SPIEGELHALTER, DJ AF FREEDMAN, LS SPIEGELHALTER, DJ TI APPLICATION OF BAYESIAN STATISTICS TO DECISION-MAKING DURING A CLINICAL-TRIAL SO STATISTICS IN MEDICINE LA English DT Article ID INTERIM ANALYSES AB We describe the application of Bayesian methods to the monitoring and analysis of a trial of treatment for patients with advanced colorectal carcinoma. We discuss the choice of prior distribution and justify the use of a truncated normal distribution with a probability mass at zero difference. The stopping rule, based on the trials of the posterior distribution and a chosen range of equivalence, yields an upper boundary very close to the Pocock group sequential boundary. The Bayes stopping rule is quite sensitive to the amount of probability mass at zero in the prior distribution. C1 MRC,BIOSTAT UNIT,CAMBRIDGE CB2 2BW,ENGLAND. RP FREEDMAN, LS (reprint author), NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,EXECUT PLAZA N,BETHESDA,MD 20892, USA. NR 19 TC 32 Z9 32 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 15 PY 1992 VL 11 IS 1 BP 23 EP 35 PG 13 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA HC732 UT WOS:A1992HC73200004 PM 1557573 ER PT J AU ELLENBERG, SS AF ELLENBERG, SS TI RANDOMIZED CONSENT DESIGNS FOR CLINICAL-TRIALS - AN UPDATE SO STATISTICS IN MEDICINE LA English DT Letter ID BREAST-CANCER RP ELLENBERG, SS (reprint author), NIAID,BIOSTAT RES BRANCH,6003 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 4 TC 4 Z9 4 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 15 PY 1992 VL 11 IS 1 BP 131 EP 132 PG 2 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA HC732 UT WOS:A1992HC73200011 PM 1557570 ER PT J AU SMITH, WL ELING, TE KULMACZ, RJ MARNETT, LJ TSAI, AL AF SMITH, WL ELING, TE KULMACZ, RJ MARNETT, LJ TSAI, AL TI TYROSYL RADICALS AND THEIR ROLE IN HYDROPEROXIDE-DEPENDENT ACTIVATION AND INACTIVATION OF PROSTAGLANDIN ENDOPEROXIDE SYNTHASE SO BIOCHEMISTRY LA English DT Article ID ANTI-INFLAMMATORY DRUGS; HIGHER OXIDATION-STATES; SHEEP VESICULAR GLAND; H-SYNTHASE; PEROXIDASE REACTION; ARACHIDONIC-ACID; SOYBEAN LIPOXYGENASE-1; COMPLEMENTARY-DNA; FATTY-ACIDS; CYCLOOXYGENASE C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. UNIV TEXAS,HLTH SCI CTR,DEPT INTERNAL MED,HOUSTON,TX 77225. VANDERBILT UNIV,MED CTR,SCH MED,AB HANCOOK JR MEM LAB CANC RES,DEPT BIOCHEM,CTR MOLEC TOXICOL,NASHVILLE,TN 37232. VANDERBILT UNIV,MED CTR,SCH MED,DEPT CHEM,NASHVILLE,TN 37232. RP SMITH, WL (reprint author), MICHIGAN STATE UNIV,DEPT BIOCHEM,E LANSING,MI 48824, USA. FU NIDDK NIH HHS [DK22042, DK42509]; NIGMS NIH HHS [GM30509] NR 52 TC 140 Z9 140 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 14 PY 1992 VL 31 IS 1 BP 3 EP 7 DI 10.1021/bi00116a001 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GZ438 UT WOS:A1992GZ43800001 PM 1731880 ER PT J AU WONG, G SKOLNICK, P AF WONG, G SKOLNICK, P TI HIGH-AFFINITY LIGANDS FOR DIAZEPAM-INSENSITIVE BENZODIAZEPINE RECEPTORS SO EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION LA English DT Article DE BENZODIAZEPINE RECEPTORS; RO-15-4513; RO-19-4603; ANNELATED 1,4-DIAZEPINES; GABA ID ALCOHOL SENSITIVITY; INVERSE AGONIST; RO 15-4513; ANTAGONIST; ETHANOL; RAT; IMIDAZOBENZODIAZEPINE; RO-15-4513; RO15-4513; BINDING AB Structurally diverse compounds have been shown to possess high affinities for benzodiazepine receptors in their 'diazepam-sensitive' (DS) conformations. In contrast, only the imidazobenzodiazepinone Ro 15-4513 has been shown to exhibit a high affinity for the 'diazepam-insensitive' (DI) conformation of benzodiazepine receptors. We examined a series of 1,4-diazepines containing one or more annelated ring systems for their affinities at DI and DS benzodiazepine receptors. several 1,4-diazepinone carboxylates including Ro 19-4603, Ro 16-6028 and Ro 15-3505 were found to possess high affinities (K(i) approximately 2.6-20 nM) for DI. Nonetheless, among the ligands examined, Ro 15-4513 was the only substance with a DI/DS potency ratio approximately 1; other substances had ratios ranging from 13 to > 1000. Ligands with high to moderate affinities at DI were previously classified as partial agonists, antagonists, or partial inverse agonists at DS benzodiazepine receptors, but behaved as 'GABA neutral' (antagonist) substances at DI. The identification of several additional high affinity ligands at DI benzodiazepine receptors may be helpful in elucidating the pharmacological and physiological importance of these sites. RP WONG, G (reprint author), NIDDK,NEUROSCI LAB,BLDG 8,RM 111,BETHESDA,MD 20892, USA. NR 32 TC 81 Z9 81 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0922-4106 J9 EUR J PHARM-MOLEC PH JI Eur. J. Pharmacol.-Molec. Pharmacol. Sect. PD JAN 14 PY 1992 VL 225 IS 1 BP 63 EP 68 DI 10.1016/0922-4106(92)90040-3 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HA887 UT WOS:A1992HA88700010 PM 1311690 ER PT J AU SMITH, CC HAUSER, E RENAUD, NK LEFF, A AKSENTIJEVICH, S CHROUSOS, GP WILDER, RL GOLD, PW STERNBERG, EM AF SMITH, CC HAUSER, E RENAUD, NK LEFF, A AKSENTIJEVICH, S CHROUSOS, GP WILDER, RL GOLD, PW STERNBERG, EM TI INCREASED HYPOTHALAMIC [H-3] FLUNITRAZEPAM BINDING IN HYPOTHALAMIC PITUITARY-ADRENAL AXIS HYPORESPONSIVE LEWIS RATS SO BRAIN RESEARCH LA English DT Article DE BENZODIAZEPINE RECEPTOR; CORTICOSTERONE; HYPOTHALAMIC PITUITARY ADRENAL AXIS; LEWIS RAT; FISCHER RAT; CIRCADIAN RHYTHM; ADRENALECTOMY ID BENZODIAZEPINE RECEPTOR-BINDING; CORTICOTROPIN-RELEASING HORMONE; CORTISOL SECRETION; BRAIN; ALPRAZOLAM; SUSCEPTIBILITY; MODULATION; ARTHRITIS; DIAZEPAM; INVITRO AB We have previously demonstrated that susceptibility of Lewis (LEW/N) rats to inflammatory disease, compared to relatively resistant Fischer (F344/N) rats, is related to deficient glucocorticoid counter-regulation of the immune response resulting from deficient corticotropin-releasing hormone (CRH) responsiveness to inflammatory and other stress mediators. The GABA/benzodiazepine receptor complex is an important negative modulator of CRH secretion and responsiveness to excitatory stimuli. In this study, we have examined in vitro binding of [H-3]flunitrazepam to hypothalamic membrane preparations from LEW/N and F344/N rats. LEW/N rats had significantly more hypothalamic benzodiazepine binding sites (B(max)) than F344/N rats, but there were no differences in benzodiazepine binding affinities (K(d)) between these two strains. The differences in benzodiazepine receptor number were consistent with the respective plasma corticosterone levels in the two strains, and with previous work indicating a negative correlation between corticosterone levels and benzodiazepine binding site number. Adrenalectomy of F344/N rats increased benzodiazepine binding to levels comparable to LEW/N animals and treatment of adrenalectomized F344/N rats with DEX resulted in lowering of benzodiazepine B(max) to levels that did not differ significantly from those of intact F344/N rats. There was no significant change in receptor number in either adrenalectomized or DEX-treated LEW/N rats. These findings suggest that basal benzodiazepine receptor differences between these strains may be partially related to strain differences in corticosterone levels, however that additional factors may contribute to maintenance of these differences in LEW/N rats. Since benzodiazepines attenuate hyphothalamic CRH secretion through GABAergic inhibition, we suggest that strain differences in receptor number could also augment strain differences in hypothalamic-pituitary-adrenal axis function through differential sensitivity to GABA-mediated feedback. C1 NICHHD,CLIN NEUROENDOCRINOL BRANCH,NEUROENDOCRINE IMMUNOL & BEHAV UNIT,BETHESDA,MD 20892. NICHHD,PEDIAT ENDOCRINOL SECT,BETHESDA,MD 20892. NIMH,NIAMS,ARTHRITIS & RHEUMATISM BRANCH,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. NIMH,NEUROENDOCRINE IMMUNOL & BEHAV UNIT,BETHESDA,MD 20892. NR 24 TC 31 Z9 31 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 13 PY 1992 VL 569 IS 2 BP 295 EP 299 DI 10.1016/0006-8993(92)90642-M PG 5 WC Neurosciences SC Neurosciences & Neurology GA HC618 UT WOS:A1992HC61800014 PM 1311618 ER PT J AU ZWANZIG, R AF ZWANZIG, R TI A SHORTCUT TO IRREVERSIBILITY - A CITATION-CLASSIC COMMENTARY ON ENSEMBLE METHOD IN THE THEORY OF IRREVERSIBILITY BY ZWANZIG,R. SO CURRENT CONTENTS/ENGINEERING TECHNOLOGY & APPLIED SCIENCES LA English DT Article RP ZWANZIG, R (reprint author), NIDDK, CHEM PHYS LAB, BETHESDA, MD 20892 USA. NR 8 TC 0 Z9 0 U1 1 U2 2 PU INST SCI INFORM INC PI PHILADELPHIA PA 3501 MARKET ST, PHILADELPHIA, PA 19104 USA SN 0011-3395 J9 CC/ENG TECH APPL SCI PD JAN 13 PY 1992 IS 2 BP 8 EP 8 PG 1 WC Multidisciplinary Sciences; Social Sciences, Interdisciplinary SC Science & Technology - Other Topics; Social Sciences - Other Topics GA GV988 UT WOS:A1992GV98800001 ER PT J AU ZWANZIG, R AF ZWANZIG, R TI A SHORTCUT TO IRREVERSIBILITY - A CITATION-CLASSIC COMMENTARY ON ENSEMBLE METHOD IN THE THEORY OF IRREVERSIBILITY BY ZWANZIG,R. SO CURRENT CONTENTS/PHYSICAL CHEMICAL & EARTH SCIENCES LA English DT Article RP ZWANZIG, R (reprint author), NIDDK, CHEM PHYS LAB, BETHESDA, MD 20892 USA. NR 8 TC 0 Z9 0 U1 1 U2 3 PU INST SCI INFORM INC PI PHILADELPHIA PA 3501 MARKET ST, PHILADELPHIA, PA 19104 USA SN 0163-2574 J9 CC/PHYS CHEM EARTH PD JAN 13 PY 1992 IS 2 BP 8 EP 8 PG 1 WC Multidisciplinary Sciences; Social Sciences, Interdisciplinary SC Science & Technology - Other Topics; Social Sciences - Other Topics GA GV990 UT WOS:A1992GV99000001 ER PT J AU ABE, O ABE, R ASAISHI, K ENOMOTO, K HATTORI, T INO, Y KIKUCHI, K KOYAMA, H SAWA, K UCHINO, J YOSHIDA, M HAYBITTLE, JL VANDEVELDE, T VERMORKEN, JB HARVEY, VJ HOLDAWAY, TM KAY, RG MASON, BH FORBES, JF BASTERT, G SAUERBREI, W SCHEURLEN, H SCHUMACHER, M FOCAN, C LOBELLE, JP PEEK, U OATES, GD POWELL, J DURAND, M MAURIAC, L GELMAN, RS HENDERSON, IC SHAPIRO, CL HANCOCK, AK JACKSON, S RAGAZ, J HENDERSON, IC KORZUN, A WOOD, WC YOSHIMOTO, M BAUM, M HOUGHTON, J HORGAN, K HUGHES, L STEWART, HJ GORDON, NH DAVIS, HL DELOZIER, T MACELESECH, J RAMBERT, P ANDRYSEK, O BARKMANOVA, J OWEN, JR HOWELL, A RIBEIRO, GC SWINDELL, R DEOLIVEIRA, CF CARSTENSEN, B PALSHOF, T JOHANSEN, H KORZENIOWSKI, S SKOLYSZEWSKI, J ANDERSEN, KW DOMBERNOWSKY, P MOURIDSEN, HT ROSE, C CORCORAN, N TRAMPISCH, HJ ABELOFF, MD CARBONE, PC GLICK, J GRAY, R TORMEY, DC BUYSE, M MIGNOLET, F PARIDAENS, R VANDRIEL, OJR SYLVESTER, RJ VANDEVELDE, CJH VANDONGEN, JA WELVAART, K SCANLON, EF SCHURMAN, S CATALANO, R CREECH, RH DESCHRYVER, A MCGREGOR, K YOSEF, HMA MCARDLE, CS SMITH, DC LARA, PC DENT, DM GUDGEON, CA HACKING, A BOCCARDO, F IZUO, M BENTLEY, A DORAN, Z FENTIMAN, IS HAYWARD, JL RUBENS, RD KAUFMANN, M JONAT, W SCHEURLEN, H VONFOURNIER, D KAUFMANN, M KLEFSTROM, P CUZICK, J MARGREITER, R ASSELAIN, B POUILLARD, P BAHI, J MILLA, A SANCHIZ, F CASTIGLIONE, M CAVALLI, F COLLINS, J GELBER, RD GOLDHIRSCH, A ISLEY, MR LINDTNER, J PRICE, KN RUDENSTAM, CM SENN, HJ BLISS, JM CHILVERS, CED COOMBES, RC MARTY, M BOROVIK, R BRUFMAN, G ROBINSON, E PANNUTI, F TAKASHIMA, S YASUTOMI, T HOLM, LE SONOO, H YAMASHITA, J BONTE, J BUZDAR, AU SMITH, T MARTIN, P ROMAIN, S AHMANN, D SCHAID, DJ HAKES, T NORTON, L WITTES, R FOROGLOU, P LISSAIOS, B BONADONNA, G DELVECCHIO, M VALAGUSSA, P VERONESI, U DUBOIS, JB BRUFMAN, G HAYAT, H BIANCO, AR LIPPMAN, ME PIERCE, LJ SIMON, R STEINBERG, SM NOMURA, Y DELAHUERTA, R SAINZ, MG BROWN, A FISHER, B REDMOND, C WOLMARK, N BAUM, M JACKSON, IM PALMER, MK INGLE, JN SCHAID, DJ BENGTSSON, NO LARSSON, LG LYTHGOE, JP SWINDELL, R KISSIN, M BLAMEY, RW MITCHELL, AK ROBERTSON, JFR CASTIGLIONE, M FLUCKIGER, H SENN, HJ NAKAMURA, Y MATHE, G MISSET, JL DESHPANDE, N DIMARTINO, L CLARKE, EA MCLAUGHLIN, JR CLARK, RM LEVINE, M MORIMOTO, K GUNDERSEN, S HAUERJENSEN, M HOST, H CROSSLEY, E DURRANT, K HARRIS, A CLARKE, M COLLINS, R GODWIN, J GRAY, R GREAVES, E HARWOOD, C MEAD, G PETO, R WHEATLEY, K HILL, C LACOUR, J LAPLANCHE, A LE, M SARRAZIN, D SEMIGLAZOV, V BROCKSCHMIDT, J COOPER, MR MEAKIN, JW PANZARELLA, T PRITCHARD, KI TREURNIETDONKER, AD VANPUTTEN, WLJ EASTON, D POWLES, TJ GAZET, JC DOUGLAS, P HACKING, A HOST, H LINDTNER, A NOTTER, G BRYANT, AJS EWING, GH KRUSHEN, JL NISSENMEYER, R FORREST, APM MCDONALD, C STEWART, HJ MOLLER, TR RYDEN, S CARSTENSEN, J HATSCHEK, T SODERBERG, M CARPENTER, JT CRAWLEY, J GREEN, S OSBORNE, CK RUTQVIST, LE WALLGREN, A BRENNER, H HERCBERGS, A DEBOER, G PATERSON, AHG PRITCHARD, KI NAJA, A REID, M SPITTLE, M SENANAYAKE, F MEIER, P TENGRUP, I TENNVALLNITTBY, L CAFFIER, H BEZWODA, WR HOLMBERG, L SEVELDA, P ZIELINSKY, CC JAKESZ, R BUCHANAN, RB CROSS, M DUNN, JA GILLESPIE KELLY, K MORRISON, JM LITTON, A CHLEBOWSKI, RT AF ABE, O ABE, R ASAISHI, K ENOMOTO, K HATTORI, T INO, Y KIKUCHI, K KOYAMA, H SAWA, K UCHINO, J YOSHIDA, M HAYBITTLE, JL VANDEVELDE, T VERMORKEN, JB HARVEY, VJ HOLDAWAY, TM KAY, RG MASON, BH FORBES, JF BASTERT, G SAUERBREI, W SCHEURLEN, H SCHUMACHER, M FOCAN, C LOBELLE, JP PEEK, U OATES, GD POWELL, J DURAND, M MAURIAC, L GELMAN, RS HENDERSON, IC SHAPIRO, CL HANCOCK, AK JACKSON, S RAGAZ, J HENDERSON, IC KORZUN, A WOOD, WC YOSHIMOTO, M BAUM, M HOUGHTON, J HORGAN, K HUGHES, L STEWART, HJ GORDON, NH DAVIS, HL DELOZIER, T MACELESECH, J RAMBERT, P ANDRYSEK, O BARKMANOVA, J OWEN, JR HOWELL, A RIBEIRO, GC SWINDELL, R DEOLIVEIRA, CF CARSTENSEN, B PALSHOF, T JOHANSEN, H KORZENIOWSKI, S SKOLYSZEWSKI, J ANDERSEN, KW DOMBERNOWSKY, P MOURIDSEN, HT ROSE, C CORCORAN, N TRAMPISCH, HJ ABELOFF, MD CARBONE, PC GLICK, J GRAY, R TORMEY, DC BUYSE, M MIGNOLET, F PARIDAENS, R VANDRIEL, OJR SYLVESTER, RJ VANDEVELDE, CJH VANDONGEN, JA WELVAART, K SCANLON, EF SCHURMAN, S CATALANO, R CREECH, RH DESCHRYVER, A MCGREGOR, K YOSEF, HMA MCARDLE, CS SMITH, DC LARA, PC DENT, DM GUDGEON, CA HACKING, A BOCCARDO, F IZUO, M BENTLEY, A DORAN, Z FENTIMAN, IS HAYWARD, JL RUBENS, RD KAUFMANN, M JONAT, W SCHEURLEN, H VONFOURNIER, D KAUFMANN, M KLEFSTROM, P CUZICK, J MARGREITER, R ASSELAIN, B POUILLARD, P BAHI, J MILLA, A SANCHIZ, F CASTIGLIONE, M CAVALLI, F COLLINS, J GELBER, RD GOLDHIRSCH, A ISLEY, MR LINDTNER, J PRICE, KN RUDENSTAM, CM SENN, HJ BLISS, JM CHILVERS, CED COOMBES, RC MARTY, M BOROVIK, R BRUFMAN, G ROBINSON, E PANNUTI, F TAKASHIMA, S YASUTOMI, T HOLM, LE SONOO, H YAMASHITA, J BONTE, J BUZDAR, AU SMITH, T MARTIN, P ROMAIN, S AHMANN, D SCHAID, DJ HAKES, T NORTON, L WITTES, R FOROGLOU, P LISSAIOS, B BONADONNA, G DELVECCHIO, M VALAGUSSA, P VERONESI, U DUBOIS, JB BRUFMAN, G HAYAT, H BIANCO, AR LIPPMAN, ME PIERCE, LJ SIMON, R STEINBERG, SM NOMURA, Y DELAHUERTA, R SAINZ, MG BROWN, A FISHER, B REDMOND, C WOLMARK, N BAUM, M JACKSON, IM PALMER, MK INGLE, JN SCHAID, DJ BENGTSSON, NO LARSSON, LG LYTHGOE, JP SWINDELL, R KISSIN, M BLAMEY, RW MITCHELL, AK ROBERTSON, JFR CASTIGLIONE, M FLUCKIGER, H SENN, HJ NAKAMURA, Y MATHE, G MISSET, JL DESHPANDE, N DIMARTINO, L CLARKE, EA MCLAUGHLIN, JR CLARK, RM LEVINE, M MORIMOTO, K GUNDERSEN, S HAUERJENSEN, M HOST, H CROSSLEY, E DURRANT, K HARRIS, A CLARKE, M COLLINS, R GODWIN, J GRAY, R GREAVES, E HARWOOD, C MEAD, G PETO, R WHEATLEY, K HILL, C LACOUR, J LAPLANCHE, A LE, M SARRAZIN, D SEMIGLAZOV, V BROCKSCHMIDT, J COOPER, MR MEAKIN, JW PANZARELLA, T PRITCHARD, KI TREURNIETDONKER, AD VANPUTTEN, WLJ EASTON, D POWLES, TJ GAZET, JC DOUGLAS, P HACKING, A HOST, H LINDTNER, A NOTTER, G BRYANT, AJS EWING, GH KRUSHEN, JL NISSENMEYER, R FORREST, APM MCDONALD, C STEWART, HJ MOLLER, TR RYDEN, S CARSTENSEN, J HATSCHEK, T SODERBERG, M CARPENTER, JT CRAWLEY, J GREEN, S OSBORNE, CK RUTQVIST, LE WALLGREN, A BRENNER, H HERCBERGS, A DEBOER, G PATERSON, AHG PRITCHARD, KI NAJA, A REID, M SPITTLE, M SENANAYAKE, F MEIER, P TENGRUP, I TENNVALLNITTBY, L CAFFIER, H BEZWODA, WR HOLMBERG, L SEVELDA, P ZIELINSKY, CC JAKESZ, R BUCHANAN, RB CROSS, M DUNN, JA GILLESPIE KELLY, K MORRISON, JM LITTON, A CHLEBOWSKI, RT TI SYSTEMIC TREATMENT OF EARLY BREAST-CANCER BY HORMONAL, CYTOTOXIC, OR IMMUNE THERAPY - 133 RANDOMIZED TRIALS INVOLVING 31000 RECURRENCES AND 24000 DEATHS AMONG 75000 WOMEN .2. SO LANCET LA English DT Review ID REQUIRING PROLONGED OBSERVATION; SURGICAL ADJUVANT BREAST; TAMOXIFEN THERAPY; CHEMOTHERAPY; IRRADIATION; PATIENT; DESIGN; TUMORS C1 INTEGRAAL KANKERCTR, AMSTERDAM, NETHERLANDS. AUCKLAND BREAST CANC STUDY GRP, AUCKLAND, NETHERLANDS. AKAD WISSENSCH DDR, O-1086 BERLIN, GERMANY. BIRMINGHAM GEN HOSP, BIRMINGHAM, ENGLAND. FDN BERGONIE, F-33076 BORDEAUX, FRANCE. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. BRADFORD ROYAL INFIRM, BRADFORD, ENGLAND. BRITISH COLUMBIA CANC FDN, VANCOUVER V5Z 3J3, BC, CANADA. CANC INST HOSP, TOKYO, JAPAN. CANC RES CAMPAIGN, LONDON, ENGLAND. CARDIFF SURG TRIALISTS, CARDIFF, WALES. CASE WESTERN RESERVE UNIV, CLEVELAND, OH 44106 USA. CTR REG FRANCOIS BACLESSE, CAEN, FRANCE. CTR RENE HUGUENIN, ST CLOUD, FRANCE. CHARLES UNIV, CS-11636 PRAGUE 1, CZECHOSLOVAKIA. CHELTENHAM GEN HOSP, CHELTENHAM, ENGLAND. CHRISTIE HOSP & HOLT RADIUM INST, MANCHESTER M20 9BX, LANCS, ENGLAND. COIMBRA INST ONCOL, COIMBRA, PORTUGAL. DANISH CANC REGISTRY, COPENHAGEN, DENMARK. COPENHAGEN RADIUM CTR, COPENHAGEN, DENMARK. CRACOW INST ONCOL, KRAKOW, POLAND. ST LUKES HOSP, DUBLIN, IRELAND. UNIV DUSSELDORF, W-4000 DUSSELDORF 1, GERMANY. EUROPEAN ORG RES TREATMENT CANC, BRUSSELS, BELGIUM. EASTERN COOPERAT ONCOL GRP, BOSTON, MA USA. DANISH BREAST CANC COOPERAT GRP, COPENHAGEN, DENMARK. CANC & LEUKEMIA GRP B, BROOKLINE, MA USA. EVANSTON HOSP CORP, EVANSTON, IL 60201 USA. FOX CHASE CANC INST, PHILADELPHIA, PA 19111 USA. STATE UNIV GHENT HOSP, B-9000 GHENT, BELGIUM. GLASCOW BEATSON ONCOL CTR, GLASGOW, SCOTLAND. VICTORIA INFIRM, GLASGOW G42 9TY, SCOTLAND. GRANADA UNIV HOSP, GRANADA, SPAIN. GROOTE SCHUUR HOSP, CAPE TOWN 7925, SOUTH AFRICA. GUNMA UNIV, MAEBASHI, GUNMA 371, JAPAN. GUYS HOSP, LONDON SE1 9RT, ENGLAND. UNIV HEIDELBERG, W-6900 HEIDELBERG, GERMANY. UNIV HEIDELBERG 2, HEIDELBERG, GERMANY. UNIV HEIDELBERG 1, HEIDELBERG, GERMANY. DEACONESS MED CTR, HELSINKI, FINLAND. IMPERIAL CANC RES FUND, LONDON WC2A 3PX, ENGLAND. UNIV INNSBRUCK, A-6020 INNSBRUCK, AUSTRIA. INST CURIE, F-75231 PARIS 05, FRANCE. INST SALAH AZAIZ, TUNIS, TUNISIA. INST POLICLIN, BARCELONA, SPAIN. INT LUDWIG BREAST CANC STUDY GRP, LONDON, ENGLAND. CHARING CROSS HOSP, INT COLLABORAT CANC GRP, LONDON W6 8RP, ENGLAND. TECHNION ISRAEL INST TECHNOL, RAMBAM MED CTR, HAIFA, ISRAEL. KAROLINSKA HOSP, S-10401 STOCKHOLM 60, SWEDEN. KAWASAKI MED UNIV, KURASHIKI, OKAYAMA 70101, JAPAN. KUMAMOTO UNIV GRP, KUMAMOTO, JAPAN. ACAD HOSP ST RAFAEL, B-3000 LOUVAIN, BELGIUM. MD ANDERSON CANC CTR, HOUSTON, TX USA. LAB CANEROL BIOL APM, MARSEILLE, FRANCE. MAYO CLIN & MAYO FDN, ROCHESTER, MN 55905 USA. MEM SLOAN KETTERING CANC CTR, NEW YORK, NY 10021 USA. METAXAS MEM CANC HOSP, ATHENS, GREECE. IST NAZL STUDIO & CURA TUMORI, I-20133 MILAN, ITALY. CTR PAUL LAMARQUE, F-34033 MONTPELLIER, FRANCE. NAPLES UNIV, I-80138 NAPLES, ITALY. NCI, BETHESDA, MD 20892 USA. NATL KYUSHU CANC CTR HOSP, KYUSHU, JAPAN. NATL MED CTR, MEXICO CITY, DF, MEXICO. NATL SURG ADJUVANT PROJECT BREAST & BOWEL CANC, PITTSBURGH, PA USA. N CENT CANC TREATMENT GRP, ROCHESTER, MN USA. NORTHWICK PK HOSP & CLIN RES CTR, HARROW HA1 3UJ, MIDDX, ENGLAND. NOTTINGHAM CITY HOSP, NOTTINGHAM NG5 1PB, ENGLAND. OITA PREFECTURAL HOSP, OITA, JAPAN. ONCOL HOSP A BUSINICO, SARDINIA, FRANCE. ONTARIO CANC TREATMENT & RES FDN, TORONTO, ONTARIO, CANADA. ONTARIO CLIN ONCOL GRP, TORONTO, ONTARIO, CANADA. OSAKA CITY MED SCH, OSAKA, JAPAN. OSLO RADIUM HOSP, OSLO, NORWAY. CHURCHILL HOSP, OXFORD OX3 7LJ, ENGLAND. IMPERIAL CANC RES FUND, MRC, CLIN TRIAL SERV UNIT, OXFORD, ENGLAND. INST GUSTAVE ROUSSY, F-94805 VILLEJUIF, FRANCE. NN PETROV ONCOL RES INST, LENINGRAD 188646, USSR. PIEDMONT ONCOL ASSOC, ATLANTA, GA USA. PRINCESS MARGARET HOSP, TORONTO M4X 1K9, ONTARIO, CANADA. ROTTERDAM RADIOTHERAPEUT INST, ROTTERDAM, NETHERLANDS. ROYAL MARSDEN HOSP, INST CANC RES, LONDON, ENGLAND. ST GEORGE HOSP, LONDON, ENGLAND. SASKATCHEWAN CANC FDN, SASKATOON, SASKATCHEWAN, CANADA. SW ONCOL GRP, KANSAS CITY, KS 66103 USA. STOCKHOLM BREAST CANC STUDY GRP, STOCKHOLM, SWEDEN. TEL AVIV UNIV, IL-69978 TEL AVIV, ISRAEL. TORONTO EDMONTON BREAST CANC STUDY GRP, TORONTO, ONTARIO, CANADA. TOULOUSE CTR CLAUDIUS REGAUD, TOULOUSE, FRANCE. UNIV CHICAGO, CHICAGO, IL 60637 USA. UNIV LUND, S-22101 LUND, SWEDEN. UNIV WURZBURG, W-8700 WURZBURG, GERMANY. UNIV WITWATERSRAND, JOHANNESBURG 2001, SOUTH AFRICA. UPPSALA OREBRO CANC STUDY GRP, UPPSALA, SWEDEN. VIENNA UNIV HOSP, DEPT GYNAECOL 1, VIENNA, AUSTRIA. VIENNA UNIV HOSP, DEPT SURG 1, VIENNA, AUSTRIA. WESSEX RADIOTHERAPY CTR, WESSEX, ENGLAND. ADDENBROOKES HOSP, CAMBRIDGE CB2 2QQ, ENGLAND. RP ABE, O (reprint author), RADCLIFFE INFIRM, NUFFIELD DEPT CLIN MED, ICRF MRC CLIN TRIAL SERV UNIT, OXFORD OX2 6HE, ENGLAND. RI Jonat, Walter/E-3024-2010; McLaughlin, John/E-4577-2013; Barkmanova, Jaroslava/A-1411-2017; Brenner, Hermann/B-4627-2017 OI Barkmanova, Jaroslava/0000-0003-1406-7292; Brenner, Hermann/0000-0002-6129-1572 NR 39 TC 871 Z9 875 U1 2 U2 29 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD JAN 11 PY 1992 VL 339 IS 8785 BP 71 EP 85 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA GZ156 UT WOS:A1992GZ15600001 ER PT J AU ROSENFELD, MA YOSHIMURA, K TRAPNELL, BC YONEYAMA, K ROSENTHAL, ER DALEMANS, W FUKAYAMA, M BARGON, J STIER, LE STRATFORDPERRICAUDET, L PERRICAUDET, M GUGGINO, WB PAVIRANI, A LECOCQ, JP CRYSTAL, RG AF ROSENFELD, MA YOSHIMURA, K TRAPNELL, BC YONEYAMA, K ROSENTHAL, ER DALEMANS, W FUKAYAMA, M BARGON, J STIER, LE STRATFORDPERRICAUDET, L PERRICAUDET, M GUGGINO, WB PAVIRANI, A LECOCQ, JP CRYSTAL, RG TI INVIVO TRANSFER OF THE HUMAN CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR GENE TO THE AIRWAY EPITHELIUM SO CELL LA English DT Article ID DEPENDENT PROTEIN-KINASE; INSITU HYBRIDIZATION; CHLORIDE CHANNELS; ADENOVIRUS TYPE-5; ESCHERICHIA-COLI; MESSENGER-RNAS; CELL-LINE; EXPRESSION; DNA; IDENTIFICATION AB Direct transfer of the normal cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene to airway epithelium was evaluated using a replication-deficient recombinant adenovirus (Ad) vector containing normal human CFTR cDNA (Ad-CFTR). In vitro Ad-CFTR-infected CFPAC-1 CF epithelial cells expressed human CFTR mRNA and protein and demonstrated correction of defective cAMP-mediated Cl-permeability. Two days after in vivo intratracheal introduction of Ad-CFTR in cotton rats, in situ analysis demonstrated human CFTR gene expression in lung epithelium. PCR amplification of reverse transcribed lung RNA demonstrated human CFTR transcripts derived from Ad-CFTR, and Northern analysis of lung RNA revealed human CFTR transcripts for up to 6 weeks. Human CFTR protein was detected in epithelial cells using anti-human CFTR antibody 11-14 days after infection. While the safety and effectiveness remain to be demonstrated, these observations suggest the feasibility of in vivo CFTR gene transfer as therapy for the pulmonary manifestations of CF. C1 TRANSGENE SA,STRASBOURG,FRANCE. INST GUSTAVE ROUSSY,F-94805 VILLEJUIF,FRANCE. JOHNS HOPKINS UNIV,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21205. RP ROSENFELD, MA (reprint author), NHLBI,PULM BRANCH,BETHESDA,MD 20892, USA. FU NHLBI NIH HHS [HL 47122, HL 40178] NR 53 TC 879 Z9 885 U1 9 U2 40 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JAN 10 PY 1992 VL 68 IS 1 BP 143 EP 155 DI 10.1016/0092-8674(92)90213-V PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GZ583 UT WOS:A1992GZ58300016 PM 1370653 ER PT J AU DECOSTA, BR RADESCA, L DIPAOLO, L BOWEN, WD AF DECOSTA, BR RADESCA, L DIPAOLO, L BOWEN, WD TI SYNTHESIS, CHARACTERIZATION, AND BIOLOGICAL EVALUATION OF A NOVEL CLASS OF N-(ARYLETHYL)-N-ALKYL-2-(1-PYRROLIDINYL)ETHYLAMINES - STRUCTURAL REQUIREMENTS AND BINDING-AFFINITY AT THE SIGMA-RECEPTOR SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID GUINEA-PIG BRAIN; ANTIPSYCHOTIC-DRUGS; OPIOID RECEPTOR; LIGANDS; AGONIST; RAT AB By synthesizing and testing a part-structure, N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (3), derived from our previously reported high affinity sigma-receptor ligands (1S,2R)-(-)-N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)cyclohexylamine [(-)-2] and (+)-2, we have identified a novel class of superpotent (subnanomolar affinity) sigma-ligands specific for the a receptor labeled by [H-3]-(+)-3-PPP. When 3 was tested for its capacity to displace [H-3]-(+)-3-PPP from guinea pig brain membranes, it exhibited a K(i) of 0.34 nM, which is better than either of its parent compounds (-)-2 (K(i) = 1.3 nM) and (+)-2 (K(i) = 6.0 nM). Other compounds related to 3 such as N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-homopiperidinyl)ethylamine (19) exhibited K(i) = 0.17 nM ([H-3]-(+)-3-PPP). The determinants for high sigma-receptor affinity of 3 were examined by manipulation of this structure in a number of different ways. The high efficacy of these compounds for the sigma-receptor, their relative chemical simplicity and ease of synthesis, and their high degree of selectivity identifies N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (3) and related compounds as a highly promising base for determination of the functional role of sigma-receptors as well as the development of novel therapeutic agents. C1 BROWN UNIV,DIV BIOL & MED,BIOCHEM SECT,PROVIDENCE,RI 02912. RP DECOSTA, BR (reprint author), NIDDKD,MED CHEM LAB,BETHESDA,MD 20892, USA. FU NIDA NIH HHS [DA04988]; NINDS NIH HHS [NS26746] NR 32 TC 71 Z9 72 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JAN 10 PY 1992 VL 35 IS 1 BP 38 EP 47 DI 10.1021/jm00079a004 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA GZ484 UT WOS:A1992GZ48400004 PM 1310114 ER PT J AU LEWIN, AH GAO, YG ABRAHAM, P BOJA, JW KUHAR, MJ CARROLL, FI AF LEWIN, AH GAO, YG ABRAHAM, P BOJA, JW KUHAR, MJ CARROLL, FI TI 2-BETA-SUBSTITUTED ANALOGS OF COCAINE - SYNTHESIS AND INHIBITION OF BINDING TO THE COCAINE RECEPTOR SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CENTRAL NERVOUS-SYSTEM; H-3 COCAINE; DOPAMINE UPTAKE; LIGAND-BINDING; RAT STRIATUM; UPTAKE SITES; TRANSPORTERS; PUTAMEN; MOUSE AB The potencies of a series of 2-beta-substituted cocaine analogues to displace [H-3]-3-beta-fluorophenyl)tropane-2-beta-carboxylic acid methyl ester binding in rat striatal membranes demonstrate the requirement for a 2-beta-substituent with two hydrogen-bond acceptors. The insensitivity of the ester moiety to steric and electronic factors suggests its modification to provide site-specific irreversible ligands. C1 RES TRIANGLE INST,POB 12194,RES TRIANGLE PK,NC 27709. NIDA,ADDICT RES CTR,NEUROSCI BRANCH,BALTIMORE,MD 21224. FU NIDA NIH HHS [DA05477] NR 23 TC 90 Z9 91 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JAN 10 PY 1992 VL 35 IS 1 BP 135 EP 140 DI 10.1021/jm00079a017 PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA GZ484 UT WOS:A1992GZ48400017 PM 1732520 ER PT J AU ABRAHAM, P PITNER, JB LEWIN, AH BOJA, JW KUHAR, MJ CARROLL, FI AF ABRAHAM, P PITNER, JB LEWIN, AH BOJA, JW KUHAR, MJ CARROLL, FI TI N-MODIFIED ANALOGS OF COCAINE - SYNTHESIS AND INHIBITION OF BINDING TO THE COCAINE RECEPTOR SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID UPTAKE SITES; STRIATAL MEMBRANES; NONHUMAN-PRIMATES; HIGH-AFFINITY; H-3 COCAINE; DOPAMINE; NORCOCAINE; LIGAND; DRUGS; MOUSE AB Cocaine methiodide (2), N-norcocaine (1b), N-benzyl-N-norcocaine (1c), and N-nor-N-acetylcocaine (1d) were synthesized and evaluated for their ability to inhibit binding of [H-3]-3-beta-(4-fluorophenyl)tropane-2-beta-carboxylic acid methyl ester (WIN 35,428) to the cocaine receptor. The study showed that removal of the N-methyl group to give 1b, or replacement with the larger N-benzyl group to give 1c, has a relatively small effect on binding potency. In contrast, replacement of the N-methyl group by the acetyl moiety to give 1d, or the addition of a methyl group to give 2, reduces affinity for the receptor by a large factor. In order to gain preliminary information concerning the importance of the nitrogen location on the tropane ring system, the receptor binding affinity of 8-methyl-8-azabicyclo[3.2.1]octan-3-beta-ol benzoate (5, beta-tropacocaine) was compared to that of the isomeric 6-methyl-6-azabicyclo[3.2.1]octan-3-beta-ol benzoate (4d). The fact that both compounds have similar binding affinities for the cocaine receptor suggests that 3-beta-(benzoyloxy)-6-methyl-6-azabicyclo[3.2.1]octane-2-carboxylic acid methyl ester, which is isomeric with cocaine, may possess binding potency similar to cocaine. C1 RES TRIANGLE INST,POB 12194,RES TRIANGLE PK,NC 27709. NIDA,ADDICT RES CTR,NEUROSCI BRANCH,BALTIMORE,MD 21224. FU NIDA NIH HHS [R37 DA005477, DA05477] NR 24 TC 76 Z9 76 U1 1 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JAN 10 PY 1992 VL 35 IS 1 BP 141 EP 144 DI 10.1021/jm00079a018 PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA GZ484 UT WOS:A1992GZ48400018 PM 1732521 ER PT J AU KROGSTAD, DJ GLUZMAN, IY HERWALDT, BL SCHLESINGER, PH WELLEMS, TE AF KROGSTAD, DJ GLUZMAN, IY HERWALDT, BL SCHLESINGER, PH WELLEMS, TE TI ENERGY-DEPENDENCE OF CHLOROQUINE ACCUMULATION AND CHLOROQUINE EFFLUX IN PLASMODIUM-FALCIPARUM SO BIOCHEMICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT 5TH BIOCHEMICAL PHARMACOLOGY SYMP : MEMBRANE TRANSPORT IN DISEASE AND TREATMENT CY JUL 25-26, 1991 CL OXFORD, ENGLAND ID RESISTANCE; MALARIA; RESURGENCE; MECHANISM; PARASITES; INVITRO; CULTURE; DRUG AB Chloroquine inhibits the growth of susceptible malaria parasites at low (nanomolar) concentrations because of an energy-requiring drug-concentrating mechanism in the parasite secondary lysosome (food vacuole) which is dependent on the acidification of that vesicle. Chloroquine resistance results from another energy-requiring process: efflux of chloroquine from the resistant parasite with a half-time of 2 min. Chloroquine efflux is inhibited reversibly by the removal of metabolizable substrate (glucose); it is also reduced by the ATPase inhibitor vanadate. These results suggest that chloroquine efflux is an energy-requiring process dependent on the generation and hydrolysis of ATP. Chloroquine efflux cannot be explained by differences in drug accumulation between chloroquine-susceptible and -resistant parasites because the 40-50-fold difference in initial efflux rates between -susceptible and -resistant parasites is unchanged when both parasites contain the same amount of chloroquine. Although chloroquine efflux is phenotypically similar to the efflux of anticancer drugs from multidrug-resistant (mdr) mammalian cells, it is not linked to either of the mdr-like genes of the parasite. C1 WASHINGTON UNIV,SCH MED,DEPT PATHOL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT CELL BIOL,ST LOUIS,MO 63110. NIH,PARASIT DIS LAB,BETHESDA,MD 20892. RP KROGSTAD, DJ (reprint author), WASHINGTON UNIV,SCH MED,DEPT MED,BOX 8051,660 S EUCLID AVE,ST LOUIS,MO 63110, USA. RI Schlesinger, Paul/C-6049-2012 FU NIAID NIH HHS [AI 25136] NR 29 TC 81 Z9 82 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JAN 9 PY 1992 VL 43 IS 1 BP 57 EP 62 DI 10.1016/0006-2952(92)90661-2 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HB642 UT WOS:A1992HB64200011 PM 1531176 ER PT J AU WINTERHALTER, M HELFRICH, W AF WINTERHALTER, M HELFRICH, W TI BENDING ELASTICITY OF ELECTRICALLY CHARGED BILAYERS - COUPLED MONOLAYERS, NEUTRAL SURFACES, AND BALANCING STRESSES SO JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article ID CURVATURE ELASTICITY; DOUBLE-LAYERS; MEMBRANES; FLEXOELECTRICITY; STIFFNESS AB We investigate in terms of Poisson-Boltzmann theory the contribution of electrostatic double layers to the bending elasticity of charged symmetric bilayers, considering in detail three special problems: first, the coupling of the monolayers by the electric field traversing a curved bilayer; second, the dependence of the elastic moduli on the position of the monolayer's neutral surface; and third, the role of the mechanical stresses balancing the electric ones. According to the results the tendency of charged membranes toward spontaneous vesiculation may be stronger than hitherto expected. C1 NIDDK,LBM,BETHESDA,MD 20892. FREE UNIV BERLIN,FACHBEREICH PHYS,W-1000 BERLIN 33,GERMANY. RI Wunder, Stephanie/B-5066-2012; Zdilla, Michael/B-4145-2011 NR 17 TC 131 Z9 132 U1 3 U2 26 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3654 J9 J PHYS CHEM-US JI J. Phys. Chem. PD JAN 9 PY 1992 VL 96 IS 1 BP 327 EP 330 DI 10.1021/j100180a060 PG 4 WC Chemistry, Physical SC Chemistry GA GZ697 UT WOS:A1992GZ69700060 ER PT J AU WELLEMS, TE AF WELLEMS, TE TI MALARIA - HOW CHLOROQUINE WORKS SO NATURE LA English DT Editorial Material ID PLASMODIUM-FALCIPARUM; RESISTANCE RP WELLEMS, TE (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. NR 14 TC 31 Z9 32 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JAN 9 PY 1992 VL 355 IS 6356 BP 108 EP 109 DI 10.1038/355108a0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GY629 UT WOS:A1992GY62900023 PM 1729645 ER PT J AU SAAG, MS POWDERLY, WG CLOUD, GA ROBINSON, P GRIECO, MH SHARKEY, PK THOMPSON, SE SUGAR, AM TUAZON, CU FISHER, JF HYSLOP, N JACOBSON, JM HAFNER, R DISMUKES, WE AF SAAG, MS POWDERLY, WG CLOUD, GA ROBINSON, P GRIECO, MH SHARKEY, PK THOMPSON, SE SUGAR, AM TUAZON, CU FISHER, JF HYSLOP, N JACOBSON, JM HAFNER, R DISMUKES, WE TI COMPARISON OF AMPHOTERICIN-B WITH FLUCONAZOLE IN THE TREATMENT OF ACUTE AIDS-ASSOCIATED CRYPTOCOCCAL MENINGITIS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; FLUCYTOSINE; NEOFORMANS; EXPERIENCE AB Background. Intravenous amphotericin B, with or without flucytosine, is usually standard therapy for cryptococcal meningitis in patients with the acquired immunodeficiency syndrome (AIDS): Fluconazole, an oral triazole agent, represents a promising new approach to the treatment of cryptococcal disease. Methods. In a randomized multicenter trial, we compared intravenous amphotericin B with oral fluconazole as primary therapy for AIDS-associated acute cryptococcal meningitis. Eligible patents, in all of whom the diagnosis had been confirmed by culture, were randomly assigned in a 2:1 ratio to receive either fluconazole (200 mg per day) or amphotericin B. Treatment was considered successful if the patient had had two consecutive negative cerebrospinal fluid cultures by the end of the 10-week treatment period. Results. Of the 194 eligible patients, 131 received fluconazole and 63 received amphotericin B (mean daily dose, 0.4 mg per kilogram of body weight in patients with successful treatment and 0.5 mg per kilogram in patients with treatment failure; P = 0.34). Treatment was successful in 25 of the 63 amphotericin B recipients (40 percent; 95 percent confidence interval, 26 percent to 53 percent) and in 44 of the 131 fluconazole recipients (34 percent; 95 percent confidence interval, 25 percent to 42 percent) (P = 0.40). There was no significant difference between the groups in overall mortality due to cryptococcosis (amphotericin vs. fluconazole, 9 of 63 [14 percent] vs. 24 of 131 [18 percent]; P = 0.48); however, mortality during the first two weeks of therapy was higher in the fluconazole group (15 percent vs. 8 percent; P = 0.25). The median length of time to the first negative cerebrospinal fluid culture was 42 days (95 percent confidence interval, 28 to 71) in the amphotericin B group and 64 days (95 percent confidence interval, 53 to 67) in the fluconazole group (P = 0.25). Multivariate analyses identified abnormal mental status (lethargy, somnolence, or obtundation) as the most important predictive factor of a high risk of death during therapy (P < 0.0001). Conclusions. Fluconazole is an effective alternative to amphotericin B as primary treatment of cryptococcal meningitis in patients with AIDS. Single-drug therapy with either drug is most effective in patients who are at low risk for treatment failure. The optimal therapy for patients at high risk remains to be determined. C1 UNIV ALABAMA, SCH MED, DEPT MED, DIV INFECT DIS, BIRMINGHAM, AL 35233 USA. UNIV ALABAMA, SCH MED, CTR COMPREHENS CANC, DIV BIOSTAT, BIRMINGHAM, AL 35233 USA. WASHINGTON UNIV, SCH MED, DIV INFECT DIS, ST LOUIS, MO 63110 USA. ST LOUIS VET AFFAIRS MED CTR, ST LOUIS, MO USA. COLUMBIA UNIV, ST LUKES ROOSEVELT HOSP, SCH MED, NEW YORK, NY 10027 USA. UNIV TEXAS SAN ANTONIO, SAN ANTONIO, TX 78285 USA. AUDIE L MURPHY VET AFFAIRS HOSP, SAN ANTONIO, TX USA. EMORY UNIV, GRADY MEM HOSP, ATLANTA, GA 30322 USA. BOSTON CITY HOSP, DEPT MED, BOSTON, MA 02118 USA. BOSTON UNIV, UNIV HOSP, DEPT MED, BOSTON, MA 02215 USA. GEORGE WASHINGTON UNIV, DEPT MED, WASHINGTON, DC 20052 USA. MED COLL GEORGIA, DEPT MED, AUGUSTA, GA 30912 USA. TULANE UNIV, DEPT MED, NEW ORLEANS, LA 70118 USA. MT SINAI MED CTR, DEPT MED, DIV INFECT DIS, NEW YORK, NY 10029 USA. BRONX VET AFFAIRS MED CTR, BRONX, NY USA. NIAID, DIV AIDS, BETHESDA, MD 20892 USA. NIAID, DIV MICROBIOL & INFECT DIS, BETHESDA, MD 20892 USA. PFIZER INC, CENT RES, GROTON, CT 06340 USA. RP SAAG, MS (reprint author), UNIV ALABAMA, BIRMINGHAM VET AFFAIRS MED CTR, 700 19TH ST S, RM 2B-108, BIRMINGHAM, AL 35233 USA. FU NCRR NIH HHS [RR-00032]; NIAID NIH HHS [N01-AI-15082, NIH-NIAID-DMID-91-04] NR 25 TC 476 Z9 492 U1 1 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 9 PY 1992 VL 326 IS 2 BP 83 EP 89 DI 10.1056/NEJM199201093260202 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA GY045 UT WOS:A1992GY04500002 PM 1727236 ER PT J AU BYRNE, J NICHOLSON, HS MULVIHILL, JJ AF BYRNE, J NICHOLSON, HS MULVIHILL, JJ TI ABSENCE OF BIRTH-DEFECTS IN OFFSPRING OF WOMEN TREATED WITH DACTINOMYCIN SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 CHILDRENS NATL MED CTR,WASHINGTON,DC 20009. UNIV PITTSBURGH,PITTSBURGH,PA 15261. RP BYRNE, J (reprint author), NCI,BETHESDA,MD 20892, USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 9 PY 1992 VL 326 IS 2 BP 137 EP 137 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GY045 UT WOS:A1992GY04500021 PM 1727228 ER PT J AU HEALY, B AF HEALY, B TI RELATIVE TOXICITY OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS EVALUATED SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP HEALY, B (reprint author), NIH,BETHESDA,MD 20892, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 8 PY 1992 VL 267 IS 2 BP 209 EP 209 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GY046 UT WOS:A1992GY04600004 PM 1309267 ER PT J AU HEALY, B AF HEALY, B TI EXERCISE RADIONUCLIDE ANGIOCARDIOGRAPHY PREDICTS CARDIAC DEATH IN PATIENTS WITH CORONARY-ARTERY DISEASE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP HEALY, B (reprint author), NIH,BETHESDA,MD 20892, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 8 PY 1992 VL 267 IS 2 BP 209 EP 209 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GY046 UT WOS:A1992GY04600006 PM 1309267 ER PT J AU HEALY, B AF HEALY, B TI BETTER TREATMENT FOR CYTOMEGALOVIRUS RETINITIS IN PATIENTS WITH ACQUIRED-IMMUNODEFICIENCY-SYNDROME SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP HEALY, B (reprint author), NIH,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 8 PY 1992 VL 267 IS 2 BP 209 EP 209 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GY046 UT WOS:A1992GY04600005 PM 1309267 ER PT J AU ANDREADIS, A ROSENTHAL, ER AF ANDREADIS, A ROSENTHAL, ER TI THE NUCLEOTIDE-SEQUENCE OF LEUB FROM SALMONELLA-TYPHIMURIUM SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Note DE LEUCINE OPERON; BETA-ISOPROPYLMALATE DEHYDROGENASE; (SALMONELLA-TYPHIMURIUM) ID 3-ISOPROPYLMALATE DEHYDROGENASE GENE; LEUCINE OPERON; CLONING; DNA AB The nucleotide sequence and deduced polypeptide sequence of the Salmonella typhimurium leuB are reported, as well as a conserved region that might bind the enzyme substrate. C1 BRIGHAM & WOMENS HOSP,DEPT MED,DIV NEUROL,CTR NEUROL DIS,BOSTON,MA 02115. NIH,INST HEART LUNG & BLOOD,PULM BRANCH,BETHESDA,MD 20892. RP ANDREADIS, A (reprint author), HARVARD UNIV,SCH MED,DEPT NEUROL NEUROSCI,BOSTON,MA 02115, USA. NR 24 TC 10 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD JAN 6 PY 1992 VL 1129 IS 2 BP 228 EP 230 DI 10.1016/0167-4781(92)90493-J PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GX669 UT WOS:A1992GX66900016 PM 1730062 ER PT J AU METZGER, H AF METZGER, H TI TOWARD A BOLD NEW FORUM SO FASEB JOURNAL LA English DT Editorial Material RP METZGER, H (reprint author), NIAMSD,INTRAMURAL RES PROGRAM,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD JAN 6 PY 1992 VL 6 IS 2 BP 662 EP 662 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA GZ440 UT WOS:A1992GZ44000001 ER PT J AU PUGA, A RAYCHAUDHURI, B NEBERT, DW AF PUGA, A RAYCHAUDHURI, B NEBERT, DW TI TRANSCRIPTIONAL DEREPRESSION OF THE MURINE CYP1A-1-GENE BY MEVINOLIN SO FASEB JOURNAL LA English DT Note DE CYTOCHROME-P450; HMG COA REDUCTASE; QUINONE REDUCTASE; AH LOCUS; AH-RECEPTOR ID HYDROCARBON HYDROXYLASE INDUCTION; PROTEIN-DNA INTERACTIONS; DIOXIN-RESPONSIVE ENHANCER; CYTOCHROME P-450C GENE; POLYCYCLIC AROMATIC-HYDROCARBONS; MOUSE HEPATOMA-CELLS; COENZYME-A REDUCTASE; CIS-ACTING ELEMENTS; ENZYME-ACTIVITY; 3-HYDROXY-3-METHYLGLUTARYL COENZYME AB In mouse hepatoma Hepa-1c1c7 cultures, polycyclic aromatic compounds such as benzol[a]pyrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin) activate the Cyp1a-1 (cytochrome P(1)450) and Nmo-1[NAD(P)H:menadione oxidoreductase] genes, two members of the aromatic hydrocarbon (Ah)-responsive gene battery. Mevinolin is known to inhibit 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase (EC 1.1.1.34), the rate-limiting step in cholesterol biosynthesis. We show here that in the absence of TCDD, mevinolin markedly increases Cyp1a-1 transcription, CYP1A1 mRNA and protein levels and enzyme activity, and NMO1 mRNA concentrations. Addition of mevalonate, the product of HMG-CoA reductase activity, fails to reverse the effects of mevinolin. In fact, when used at high concentrations, mevalonate activates Cyp1a-1 transcription. Mevinolin-induced Cyp1a-1 gene activation: (1) occurs independently of the lipid content of the growth medium, (2) is not suppressed by adding 25-hydroxycholesterol, which blocks MHG-CoA reductase activity, and (3) requires a functional Ah receptor and unimpaired nuclear translocation of the receptor. It is possible that an unknown metabolite (or metabolites) of mevinolin activates Cyp1a-1 expression and that high concentrations of mevalonate act via the same mechanism. Using chimaeric plasmids that contain different lengths of Cyp1a-1 5' flanking regions fused to the bacterial neomycin (neo) gene, we find that the mevinolin effect on Cyp1a-1 induction requires the 5' flanking sequences between -1647 and -824, which are also needed for TCDD induction. Mevinolin, however, is not a ligand for the Ah receptor. Gel mobility shift assays revealed that Cyp1a-1 activation caused by mevinolin does not involve the ligand-dependent formation of a functional Ah receptor-dependent DNA-binding complex, but instead appears to be correlated with release of a putative repressor from its cognate DNA site. Our results suggest that the basel level of Cyp1a-1 transcription is maintained by an unknown negative regulatory factor. We propose that Cyp1a-1 transcriptional activation can result not only from induction by polycyclic aromatic compounds but also from derepression by mevinolin, independent of HMG-CoA reductase inhibition. C1 NICHHD,DEV PHARMACOL LAB,BETHESDA,MD 20892. RP PUGA, A (reprint author), UNIV CINCINNATI,MED CTR,DEPT ENVIRONM HLTH,3223 EDEN AVE,CINCINNATI,OH 45267, USA. RI Puga, Alvaro/B-7676-2008 NR 68 TC 24 Z9 24 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD JAN 6 PY 1992 VL 6 IS 2 BP 777 EP 785 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA GZ440 UT WOS:A1992GZ44000022 PM 1311272 ER PT J AU BERG, MM STERNBERG, DW PARADA, LF CHAO, MV AF BERG, MM STERNBERG, DW PARADA, LF CHAO, MV TI K-252A INHIBITS NERVE GROWTH FACTOR-INDUCED TRK PROTOONCOGENE TYROSINE PHOSPHORYLATION AND KINASE-ACTIVITY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID PC12 CELLS; PROTEINS; TRANSCRIPTION; EXPRESSION; INCREASE AB The rat pheochromocytoma PC12 cell line differentiates into a sympathetic neuronal phenotype upon treatment with either nerve growth factor (NGF) or basic fibroblast growth factor. The alkaloid-like compound K-252a has been demonstrated to be a specific inhibitor of NGF-induced biological responses in PC12 cells (Koizumi, S., Contreras, M. L., Matsuda, Y., Hama, T., Lazarovici, P., and Guroff, G. (1988) J. Neurosci. Res. 8, 715-721). NGF interacts with the protein product of the proto-oncogene trk and rapidly stimulates the tyrosine phosphorylation of both p140prototrk and a number of cellular substrates. Here we show that these phosphorylation events are directly inhibited in PC12 cells by K252a in a dose-dependent manner, indicating that the site of action of this inhibitor is at the NGF receptor level. K-252a inhibits p140prototrk activity in vitro, demonstrating that K252a has a direct effect on the p140prtotrk tyrosine kinase. Though many of the biochemical responses to NGF in PC12 cells are mimicked by basic fibroblast growth factor and epidermal growth factor, K-252a has no effect on the action of these growth factors in PC12 cells, demonstrating that the initial biological events initiated by NGF are distinctive during neuronal differentiation. C1 CORNELL UNIV,MED CTR,COLL MED,DEPT MED,DIV HEMATOL ONCOL,NEW YORK,NY 10021. ROCKEFELLER UNIV,MOLEC ONCOL LAB,NEW YORK,NY 10021. NCI,FREDERICK CANC RES & DEV CTR,MOLEC EMBRYOL SECT,ADV BIOSCI LAB,BASIC RES PROGRAM,FREDERICK,MD 21702. RP BERG, MM (reprint author), CORNELL UNIV,MED CTR,COLL MED,DEPT CELL BIOL & ANAT,NEW YORK,NY 10021, USA. RI Parada, luis/B-9400-2014 FU NCI NIH HHS [CA44356-05, N01-CO-741101]; NINDS NIH HHS [NS21072] NR 27 TC 331 Z9 333 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 5 PY 1992 VL 267 IS 1 BP 13 EP 16 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GY439 UT WOS:A1992GY43900004 PM 1730579 ER PT J AU RAO, PV KRISHNA, CM ZIGLER, JS AF RAO, PV KRISHNA, CM ZIGLER, JS TI IDENTIFICATION AND CHARACTERIZATION OF THE ENZYMATIC-ACTIVITY OF ZETA-CRYSTALLIN FROM GUINEA-PIG LENS - A NOVEL NADPH-QUINONE OXIDOREDUCTASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SUPEROXIDE-DISMUTASE; CARBONYL REDUCTASE; DT-DIAPHORASE; SEMI-QUINONE; PROTEIN; DEHYDROGENASES; EVOLUTION; SYSTEMS; GENE AB Zeta-crystallin is a major protein in the lens of certain mammals. In guinea pigs it comprises 10% of the total lens protein, and it has been shown that a mutation in the zeta-crystallin gene is associated with autosomal dominant congenital cataract. As with several other lens crystallins of limited phylogenetic distribution, zeta-crystallin has been characterized as an "enzyme/crystallin" based on its ability to reduce catalytically the electron acceptor 2,6-dichlorophenolindophenol. We report here that certain naturally occurring quinones are good substrates for the enzymatic activity of zeta-crystallin. Among the various quinones tested, the orthoquinones 1,2-naphthoquinone and 9,10-phenanthrenequinone were the best substrates whereas menadione, ubiquinone, 9,10-anthraquinone, vitamins K1 and K2 were inactive as substrates. This quinone reductase activity was NADPH specific and exhibited typical Michaelis-Menten kinetics. Activity was sensitive to heat and sulfhydryl reagents but was very stable on freezing. Dicumarol (K(i) = 1.3 x 10(-5) M) and nitrofurantoin (K(i) = 1.4 x 10(-5) M) inhibited the activity competitively with respect to the electron acceptor, quinone. NADPH protected the enzyme against inactivation caused by heat, N-ethylmaleimide, or H2O2. Electron paramagnetic resonance spectroscopy of the reaction products showed formation of a semiquinone radical. The enzyme activity was associated with O2 consumption, generation of O2- and H2O2, and reduction of ferricytochrome c. These properties indicate that the enzyme acts through a one-electron transfer process. The substrate specificity, reaction characteristics, and physicochemical properties of zeta-crystallin demonstrate that it is an active NADPH:quinone oxidoreductase distinct from quinone reductases described previously. C1 NEI,MECHANISMS OCULAR DIS LAB,BETHESDA,MD 20892. NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NR 36 TC 141 Z9 144 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 5 PY 1992 VL 267 IS 1 BP 96 EP 102 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GY439 UT WOS:A1992GY43900021 PM 1370456 ER PT J AU WENTHOLD, RJ YOKOTANI, N DOI, K WADA, K AF WENTHOLD, RJ YOKOTANI, N DOI, K WADA, K TI IMMUNOCHEMICAL CHARACTERIZATION OF THE NON-NMDA GLUTAMATE RECEPTOR USING SUBUNIT-SPECIFIC ANTIBODIES - EVIDENCE FOR A HETEROOLIGOMERIC STRUCTURE IN RAT-BRAIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CENTRAL NERVOUS-SYSTEM; FUNCTIONAL EXPRESSION; MOLECULAR-STRUCTURE; GLYCINE RECEPTOR; ACID; BINDING; PURIFICATION; PROTEINS; CLONING; FAMILY AB Antibodies were made to synthetic peptides corresponding to sequences specific to the glutamate receptor (GluR) subunits, GluR1-4. The specificity of the antibodies was established by Western blotting using membranes of simian kidney cells (COS-7) transfected with GluR subunit DNA. Four antibodies were found to be selective for each of the four GluR subunits, and a fifth antibody recognized both GluR2 and 3. All five antibodies immunoadsorbed Triton X-100-solubilized rat brain [H-3]AMPA binding activity and labeled an M(r) = 108,000 band in samples of rat brain. The structure of the Triton X-100-solubilized GluR was studied using subunit-specific antibodies covalently attached to protein A-agarose and analyzing GluR subunits bound to the antibodies by Western blotting. Each of the four subunit-specific antibodies immunoadsorbed its respective GluR subunit as well as the other three forms of GluR, showing that the detergent solubilized GluR exists as hetero-oligomers composed of two or more of the four subunits. Evidence supporting a similar structure for membrane bound GluR was obtained using synaptic membranes chemically cross-linked with dithiobis(succinimidylpropionate). GluR was immunoaffinity-purified using the GluR2 and 3-selective antibody. This antibody, covalently attached to protein A-agarose, adsorbed 55% of [H-3]AMPA binding activity, and after elution with 1 M KSCN, 22-37% of the binding activity was recovered. Analysis of the purified product showed a major immunoreactive band at M(r) = 108,000, and silver staining identified the same major band and no additional polypeptides. The GluR receptor complex, therefore, appears to be made up exclusively of GluR1-4. In the purified GluR preparation, in addition to the M(r) = 108,000 band, three higher molecular weight immunoreactive components were also detected. These bands migrated at M(r) = 325,000, 470,000, and 590,000. Similar sized proteins were seen in the cross-linked synaptic membrane sample, with the M(r) = 590,000 component being substantially enriched after cross-linking. The M(r) = 590,000 band is the largest component detected, and it has a size consistent with its being a pentamer of the M(r) = 108,000 protein. RP WENTHOLD, RJ (reprint author), NIDOCD,NEUROCHEM LAB,BLDG 36,RM 5D08,BETHESDA,MD 20892, USA. NR 33 TC 456 Z9 459 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 5 PY 1992 VL 267 IS 1 BP 501 EP 507 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GY439 UT WOS:A1992GY43900080 PM 1309749 ER PT J AU CORCORAN, ML STETLERSTEVENSON, WG BROWN, PD WAHL, LM AF CORCORAN, ML STETLERSTEVENSON, WG BROWN, PD WAHL, LM TI INTERLEUKIN-4 INHIBITION OF PROSTAGLANDIN-E2 SYNTHESIS BLOCKS INTERSTITIAL COLLAGENASE AND 92-KDA TYPE-IV COLLAGENASE GELATINASE PRODUCTION BY HUMAN MONOCYTES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN MONONUCLEAR PHAGOCYTES; HUMAN PERIPHERAL-BLOOD; MACROPHAGE COLLAGENASE; GENE-EXPRESSION; SYNOVIAL-CELLS; IFN-GAMMA; IDENTIFICATION; METALLOPROTEINASES AB Activation of human monocytes results in the production of interstitial collagenase through a prostaglandin E2 (PGE2)-cAMP-dependent pathway. Inasmuch as interleukin 4 (IL-4) has been shown to inhibit PGE2 synthesis by monocytes, we examined the effect of IL-4 on the production of human monocyte interstitial collagenase. Additionally, we also assessed the effect of IL-4 on the production of 92-kDa type IV collagenase/gelatinase and tissue inhibitor of metalloproteinase-1 (TIMP-1) by monocytes. The inhibition of PGE2 synthesis by IL-4 resulted in decreased interstitial collagenase protein and activity that could be restored by exogenous PGE2 or dibutyryl cyclic AMP (Bt2cAMP). IL-4 also suppressed ConA-stimulated 92-kDa type IV collagenase/gelatinase protein and zymogram enzyme activity that could be reversed by exogenous PGE2 or Bt2cAMP. Moreover, indomethacin suppressed the ConA-induced production of 92-kDa type IV collagenase/gelatinase. These data demonstrate that, like monocyte interstitial collagenase, the ConA-inducible monocyte 92-kDa type IV collagenase/gelatinase is regulated through a PGE2-mediated cAMP-dependent pathway. In contrast to ConA stimulation, unstimulated monocytes released low levels of 92-kDa type IV collagenase/gelatinase that were not affected by IL-4, PGE2, or Bt2cAMP, indicating that basal production of this enzyme is PGE2-cAMP independent. IL-4 inhibition of both collagenases was not a result of increased TIMP expression since Western analysis of 28.5-kDa TIMP-1 revealed that IL-4 did not alter the increased TIMP-1 protein in response to ConA. These data indicate that IL-4 may function in natural host regulation of connective tissue damage by monocytes. C1 NIDR,CELLULAR IMMUNOL SECT,IMMUNOL LAB,BLDG 30,RM 325,BETHESDA,MD 20892. NCI,TUMOR INVAS & METASTASIS SECT,PATHOL LAB,BETHESDA,MD 20892. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 30 TC 186 Z9 189 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 5 PY 1992 VL 267 IS 1 BP 515 EP 519 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GY439 UT WOS:A1992GY43900082 PM 1309751 ER PT J AU ROQUEMORE, EP DELL, A MORRIS, HR PANICO, M REASON, AJ SAVOY, LA WISTOW, GJ ZIGLER, JS EARLES, BJ HART, GW AF ROQUEMORE, EP DELL, A MORRIS, HR PANICO, M REASON, AJ SAVOY, LA WISTOW, GJ ZIGLER, JS EARLES, BJ HART, GW TI VERTEBRATE LENS ALPHA-CRYSTALLINS ARE MODIFIED BY O-LINKED N-ACETYLGLUCOSAMINE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RESOLUTION 2-DIMENSIONAL ELECTROPHORESIS; NON-LENTICULAR TISSUES; B-CRYSTALLIN; HEAT-SHOCK; EYE LENS; A-CHAIN; PROTEINS; PHOSPHORYLATION; GLYCOPROTEINS; GLCNAC AB Crystallins are structural proteins responsible for establishing the remarkable optical properties of the lens. Yet many of these highly conserved proteins are also expressed in nonocular tissues, where they have alternative functions apparently unrelated to their structural role in the lens. Here we report that lens alpha-crystallins, some of which function as heat-shock proteins in other tissues, are modified with O-linked N-acetylglucosamine (O-GlcNAc). An in vitro enzymatic assay that transfers [H-3]Gal to terminal GlcNAc moieties labels alpha-A and alpha-B crystallins in lens homogenates from man, rhesus monkey, rat, cow, and rhea (an ostrich-like bird). O-Linkage of the saccharide is demonstrated by sensitivity to base-catalyzed beta-elimination and resistance to peptide:N-glycosidase F treatment. Chromatographic analyses of the beta-elimination products and fast atom bombardment-mass spectrometry of [H-3]Gal-labeled tryptic peptides confirm the saccharide structure. Isoelectric focusing of [H-3]Gal-labeled bovine lens proteins reveals the presence of O-GlcNAc on all four alpha-crystallin subunits, A1, A2, B1, and B2. Electrospray mass spectrometry of bovine alpha-crystallin demonstrates the presence of a single O-GlcNAc substitution on alpha-A2. Gas-phase protein sequencing and fast atom bombardment-mass spectrometry of the major radiolabeled tryptic peptide from bovine alpha-crystallin reveal that GlcNAc is attached to the alpha-A subunits at serine 162. This post-translational modification may play an important role in the molecular organization of lens alpha-crystallin. C1 JOHNS HOPKINS UNIV, SCH MED, DEPT BIOL CHEM, 725 N WOLFE ST, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT PHARMACOL & MOLEC SCI, BALTIMORE, MD 21205 USA. IMPERIAL COLL SCI TECHNOL & MED, DEPT BIOCHEM, LONDON SW7 2AZ, ENGLAND. M SCAN LTD, ASCOT SL5 7PZ, BERKS, ENGLAND. NEI, MOLEC & DEV BIOL LAB, BETHESDA, MD 20892 USA. NEI, MECH OCULAR DIS LAB, BETHESDA, MD 20892 USA. FU NCI NIH HHS [CA42486]; NICHD NIH HHS [HD13563] NR 66 TC 84 Z9 89 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 5 PY 1992 VL 267 IS 1 BP 555 EP 563 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GY439 UT WOS:A1992GY43900087 PM 1730617 ER PT J AU JAUNIN, P HORISBERGER, JD RICHTER, K GOOD, PJ ROSSIER, BC GEERING, K AF JAUNIN, P HORISBERGER, JD RICHTER, K GOOD, PJ ROSSIER, BC GEERING, K TI PROCESSING, INTRACELLULAR-TRANSPORT, AND FUNCTIONAL EXPRESSION OF ENDOGENOUS AND EXOGENOUS ALPHA-BETA-3 NA,K-ATPASE COMPLEXES IN XENOPUS OOCYTES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-SUBUNIT; ENDOPLASMIC-RETICULUM; ALPHA-SUBUNITS; K+-ATPASE; MEMBRANE; NA+; NA+,K+-ATPASE; ALDOSTERONE; MATURATION; CELLS AB The minimal functional Na,K-ATPase unit is composed of a catalytic alpha-subunit and a glycosylated beta-subunit. So far three putative beta-isoforms have been described, but only beta-1-isoforms have been identified clearly as part of a purified active enzyme complex. In this study we provide evidence that a putative beta-3-isoform might be the functional component of Xenopus oocyte Na,K-ATPase. Beta-3-isoforms are expressed in the oocyte plasma membrane together with alpha-subunits, but beta-3-isoforms are synthesized to a lesser extent than alpha-subunits. The unassembled oocyte alpha-subunits accumulate in an immature trypsin-sensitive form most likely in the endoplasmic reticulum (ER). Injection of both beta-1- and beta-3-cRNA into oocytes abolishes the transport constraint of the oocyte alpha-subunit, renders it trypsin-resistant, and finally leads to an increased number of functional pumps at the plasma membrane. In addition, beta-3-isoforms as beta-1-isoforms depend on the concomitant synthesis of alpha-subunits to be able to leave the ER and to become fully glycosylated. Finally, alpha-beta-1 and alpha-beta-3 complexes expressed at the plasma membrane appear to have similar transport properties as assessed by ouabain binding, rubidium uptake, and electrophysiological measurements in oocytes coexpressing exogenous alpha-1- and beta-1- or beta-3-isoforms. Thus our data indicate that beta-3-isoforms have functional qualities similar to beta-1-isoforms. They can assemble and impose a structural reorganization to newly synthesized alpha-subunits which permits the exit from the ER and the expression of functional Na,K-pumps at the plasma membrane. C1 UNIV LAUSANNE,INST PHARMACOL & TOXICOL,RUE DU BUGNON 27,CH-1005 LAUSANNE,SWITZERLAND. SALZBURG UNIV,DEPT GENET,A-5020 SALZBURG,AUSTRIA. NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. RI Horisberger, Jean-Daniel/A-2538-2009 NR 27 TC 97 Z9 99 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 5 PY 1992 VL 267 IS 1 BP 577 EP 585 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GY439 UT WOS:A1992GY43900090 PM 1309755 ER PT J AU ACCILI, D KADOWAKI, T KADOWAKI, H MOSTHAF, L ULLRICH, A TAYLOR, SI AF ACCILI, D KADOWAKI, T KADOWAKI, H MOSTHAF, L ULLRICH, A TAYLOR, SI TI IMMUNOGLOBULIN HEAVY CHAIN-BINDING PROTEIN BINDS TO MISFOLDED MUTANT INSULIN-RECEPTORS WITH MUTATIONS IN THE EXTRACELLULAR DOMAIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DENSITY LIPOPROTEIN RECEPTOR; INTRACELLULAR-TRANSPORT; IMPAIRS TRANSPORT; 3T3-L1 ADIPOCYTES; PLASMA-MEMBRANE; KINASE-ACTIVITY; CYSTEINE-RICH; CELL-SURFACE; FORMS; GLYCOSYLATION AB Cell-surface proteins are transported through the endoplasmic reticulum and Golgi apparatus en route to the plasma membrane. Previously, we have identified three point mutations in the insulin receptor gene that impair transport of the mutant receptors to the cell surface: Asn15 --> Lys, His209 --> Arg, and Phe382 --> Val. Furthermore, these mutations impair post-translational processing steps that normally occur as the receptors are transported through the endoplasmic reticulum and Golgi apparatus. In this study, we have demonstrated that the unprocessed Arg209 and Val382 mutant proreceptors are bound to the immunoglobulin heavy chain-binding protein (BiP) in the endoplasmic reticulum. This was demonstrated by the fact that monoclonal anti-BiP antibody coimmunoprecipitated the mutant proreceptors. Moreover, when ATP was added to the immunoprecipitates, the mutant proreceptors were released from BiP. In contrast, neither the normal human insulin receptor nor the Lys15 mutant proreceptor was coimmunoprecipitated by anti-BiP antibody. It seems likely that the Lys 15 receptor also binds BiP, but that the affinity was too low to resist dissociation during the stringent washing of the immmunoprecipitate. In conclusion, these observation are consistent with the hypothesis that binding to BiP explains the impaired transport of mutant receptors through the endoplasmic reticulum and Golgi apparatus to the plasma membrane. C1 MAX PLANCK INST BIOCHEM,DEPT MOLEC BIOL,W-8033 MARTINSRIED,GERMANY. RP ACCILI, D (reprint author), NIDDKD,DIABET BRANCH,BLDG 10,RM 8S-243,BETHESDA,MD 20892, USA. NR 30 TC 41 Z9 41 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 5 PY 1992 VL 267 IS 1 BP 586 EP 590 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GY439 UT WOS:A1992GY43900091 PM 1730618 ER PT J AU YAMAUCHI, A UCHIDA, S KWON, HM PRESTON, AS ROBEY, RB GARCIAPEREZ, A BURG, MB HANDLER, JS AF YAMAUCHI, A UCHIDA, S KWON, HM PRESTON, AS ROBEY, RB GARCIAPEREZ, A BURG, MB HANDLER, JS TI CLONING OF A NA+-DEPENDENT AND CL--DEPENDENT BETAINE TRANSPORTER THAT IS REGULATED BY HYPERTONICITY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GABA; ACID; OSMOREGULATION; PROTEIN; CELLS; BLOOD; RAT AB Many hypertonic bacteria, plants, marine animals, and the mammalian renal medulla are protected from the deleterious effects of high intracellular concentrations of electrolytes by accumulating high concentrations of the nonperturbing osmolyte betaine. When kidney-derived Madin-Darby canine kidney (MDCK) cells are cultured in hypertonic medium, they accumulate betaine to 1,000 times its medium concentration. This results from induction by hypertonicity of high rates of betaine transport into cells. We have isolated a cDNA (BGT-1) encoding a renal betaine transporter by screening an MDCK cell cDNA library for expression of a betaine transporter in Xenopus oocytes. The cDNA encodes a single protein of 614 amino acids, with an estimated molecular weight of 69 kDa. The deduced amino acid sequence exhibits highly significant sequence and topographic similarity to brain gamma-amino-n-butyric acid (GABA) and noradrenaline transporters, suggesting that the renal BGT-1 is a member of the brain GABA/noradrenaline transporter gene family. Expression in oocytes indicates that the BGT-1 protein has both betaine and GABA transport activities that are Cl-- as well as Na+-dependent and functionally similar to betaine and GABA transport in MDCK cells. Northern hybridization indicates that transporter mRNA is localized to the kidney medulla and is induced in MDCK cells by hypertonicity. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV NEPHROL,725 N WOLFE ST,BALTIMORE,MD 21205. NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. RI Uchida, Shinichi/D-1111-2013; Robey, R. Brooks/J-7099-2013 OI Robey, R. Brooks/0000-0001-5059-3965 NR 24 TC 365 Z9 370 U1 1 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 5 PY 1992 VL 267 IS 1 BP 649 EP 652 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GY439 UT WOS:A1992GY43900100 PM 1370453 ER PT J AU LETOURNEUR, F KLAUSNER, RD AF LETOURNEUR, F KLAUSNER, RD TI ACTIVATION OF T-CELLS BY A TYROSINE KINASE ACTIVATION DOMAIN IN THE CYTOPLASMIC TAIL OF CD3-EPSILON SO SCIENCE LA English DT Article ID MONOCLONAL-ANTIBODY; ANTIGEN RECEPTOR; COMPLEX; PHOSPHORYLATION; IDENTIFICATION; ASSOCIATION; HYBRIDOMAS; PROTEIN AB The multichain T cell antigen receptor functions by interacting with and activating one or more nonreceptor tyrosine kinases. The cytoplasmic tail of the zeta-chain can activate T cells independently of the rest of the receptor complex. The function of the remaining invariant CD3 chains remains unknown. A 22-amino acid region of the cytoplasmic tail of CD3-epsilon was also able to independently activate T cells. Stimulation of T cells by means of the cytoplasmic tails of either zeta or CD3-epsilon resulted in quantitatively distinct patterns of tyrosine phosphorylation, suggesting activation of different biochemical pathways. RP LETOURNEUR, F (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. NR 23 TC 411 Z9 411 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JAN 3 PY 1992 VL 255 IS 5040 BP 79 EP 82 DI 10.1126/science.1532456 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GX791 UT WOS:A1992GX79100041 PM 1532456 ER PT J AU DUHAMEL, JR COLBY, CL GOLDBERG, ME AF DUHAMEL, JR COLBY, CL GOLDBERG, ME TI THE UPDATING OF THE REPRESENTATION OF VISUAL SPACE IN PARIETAL CORTEX BY INTENDED EYE-MOVEMENTS SO SCIENCE LA English DT Article ID MECHANISMS; PRIMATE; MACAQUE; MEMORY AB Every eye movement produces a shift in the visual image on the retina. The receptive field, or retinal response area, of an individual visual neuron moves with the eves so that after an eye movement it covers a new portion of visual space. For some parietal neurons, the location of the receptive field is shown to shift transiently before an eve movement. In addition, nearly all parietal neurons respond when an eye movement brings the site of a previously flashed stimulus into the receptive field. Parietal cortex both anticipates the retinal consequences of eye movements and updates the retinal coordinates of remembered stimuli to generate a continuously accurate representation of visual space. C1 NEI,SENSORIMOTOR RES LAB,BLDG 10,ROOM 10C 101,BETHESDA,MD 20892. NR 13 TC 1077 Z9 1081 U1 5 U2 34 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JAN 3 PY 1992 VL 255 IS 5040 BP 90 EP 92 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GX791 UT WOS:A1992GX79100045 PM 1553535 ER PT J AU KALMAN, M MURPHY, H CASHEL, M AF KALMAN, M MURPHY, H CASHEL, M TI THE NUCLEOTIDE-SEQUENCE OF RECG, THE DISTAL SPO OPERON GENE IN ESCHERICHIA-COLI K-12 SO GENE LA English DT Note DE RECOMBINASE; RECG GENE DELETION; HELICASE; MITOMYCIN AND UV SENSITIVITIES; SOS; PPGPP; RECOMBINANT DNA ID RECOMBINATION; REPAIR; DNA AB A gene is identified in the Escherichia coli K-12 spo operon as recG. Previously identified genes in the spo operon were spoS, alias rpoZ, encoding the omega (omega) subunit of RNA polymerase, as well as the spoT gene encoding the major cellular source of guanosine 3',5'-bispyrophosphate hydrolase activity. The gene order within the spo operon is: spoS (rpoZ), spoT, spoU, recG. A convergent gltS gene is present beyond the spo operon. Mutants bearing recG deletion-insertion alleles display mild sensitivities to both ultraviolet irradiation and to mitomycin C, which is expected to be due to a known recG insertion allele. Deletion-insertion mutations in upstream operon genes (spoT and spoU) show polar effects on these assays of recG function. The deduced 693-amino acid (aa) RecG sequence shows a weak, but significant, relatedness to aa sequence motifs previously reported for putative helicases involved in replication, recombination, and DNA repair. C1 NICHHD,BLDG 6,RM 333,BETHESDA,MD 20892. NR 12 TC 22 Z9 24 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JAN 2 PY 1992 VL 110 IS 1 BP 95 EP 99 DI 10.1016/0378-1119(92)90449-Y PG 5 WC Genetics & Heredity SC Genetics & Heredity GA HE647 UT WOS:A1992HE64700013 PM 1544582 ER PT J AU LAGA, M ICENOGLE, JP MARSELLA, R MANOKA, AT NZILA, N RYDER, RW VERMUND, SH HEYWARD, WL NELSON, A REEVES, WC AF LAGA, M ICENOGLE, JP MARSELLA, R MANOKA, AT NZILA, N RYDER, RW VERMUND, SH HEYWARD, WL NELSON, A REEVES, WC TI GENITAL PAPILLOMAVIRUS INFECTION AND CERVICAL DYSPLASIA - OPPORTUNISTIC COMPLICATIONS OF HIV-INFECTION SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INTRAEPITHELIAL NEOPLASIA; LATIN-AMERICA; RISK FACTOR; CANCER; ABNORMALITIES; EPIDEMIOLOGY AB Certain human genital papillomaviruses (HPV) are strongly associated with cervical dysplasia and cancer. Evidence is accumulating that HPV infection and ano-genital cancers are more common in patients with the acquired immunodeficiency syndrome. The objective of our study was to evaluate the extent to which HPV infection and associated cervical disease constitute opportunistic complications of human immunodeficiency virus (HIV) infection in a population of sexually promiscuous, HIV-infected women in Kinshasa, Zaire. In 1989 we obtained Pap smears and cervicovaginal lavage specimens for HPV DNA testing from 47 HIV-seropositive and 48 HIV-seronegative prostitutes who were part of a cohort under observation since 1988. Thirty-eight percent of the HIV-seropositive and 8% of the seronegative women (odds ratio = 6.8; p = 0.001) had HPV DNA detected by either ViraType, a dot-blot assay which detects specific genital HPV types, or low-stringency Southern blot, which detects all HPV types. Eighty-two women (86%) had an interpretable Pap smear; 11 of 41 (27%) HIV-seropositive women and one of 41 (3%) seronegative women had cervical intra-epithelial neoplasia (CIN) (odds ratio = 14.7; p = 0.002). HIV seropositivity, HPV infection and CIN were highly associated. Eight (73%) of 11 seropositive women with CIN had HPV detected. Both HPV infection and cervical cancer may emerge as opportunistic complications of HIV infection in populations in which HIV, HPV and cervical cancer are common. C1 CTR DIS CONTROL,CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,VIRAL EXANTHEMS & HERPESVIRUS BRANCH,ATLANTA,GA 30333. ARMED FORCES INST PATHOL,WASHINGTON,DC 20306. DEPT PUBL HLTH,PROJECT SIDA,KINSHASA,ZAIRE. NIAID,DIV AIDS,EPIDEMIOL BRANCH,BETHESDA,MD 20892. OI Vermund, Sten/0000-0001-7289-8698 NR 27 TC 157 Z9 159 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 2 PY 1992 VL 50 IS 1 BP 45 EP 48 DI 10.1002/ijc.2910500110 PG 4 WC Oncology SC Oncology GA GW968 UT WOS:A1992GW96800009 PM 1309459 ER PT J AU FARCI, P ALTER, HJ WONG, D MILLER, RH SHIH, JW JETT, B PURCELL, RH AF FARCI, P ALTER, HJ WONG, D MILLER, RH SHIH, JW JETT, B PURCELL, RH TI HEPATITIS-C VIRUS-REPLICATION - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP FARCI, P (reprint author), NIH,BETHESDA,MD 20892, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 2 PY 1992 VL 326 IS 1 BP 65 EP 66 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA GX315 UT WOS:A1992GX31500016 ER PT B AU TIMS, FM AF TIMS, FM BE Tongue, F Martin, E TI TREATMENT EVALUATION AT THE NATIONAL INSTITUTE ON DRUG ABUSE SO 36TH INTERNATIONAL CONGRESS ON ALCOHOL AND DRUG DEPENDENCE, VOLS I & II LA English DT Proceedings Paper CT 36th International Congress on Alcoholism and Drug Dependence CY AUG 16-21, 1992 CL GLASGOW, SCOTLAND SP Int Council Alcohol & Addict, Socttish Council Alcohol C1 NIDA,ROCKVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT COUNCIL ALCOHOL AND ADDITIONS PI LAUSANNE PA CASE POSTALE 140, CH-1001 LAUSANNE, SWITZERLAND PY 1992 BP 1302 EP 1307 PG 6 WC Substance Abuse SC Substance Abuse GA BC59Z UT WOS:A1992BC59Z00186 ER PT B AU TIMS, FM HUBBARD, RL AF TIMS, FM HUBBARD, RL BE Tongue, F Martin, E TI DRUG ABUSE TREATMENT OUTCOME STUDY (DATOS) SO 36TH INTERNATIONAL CONGRESS ON ALCOHOL AND DRUG DEPENDENCE, VOLS I & II LA English DT Proceedings Paper CT 36th International Congress on Alcoholism and Drug Dependence CY AUG 16-21, 1992 CL GLASGOW, SCOTLAND SP Int Council Alcohol & Addict, Socttish Council Alcohol C1 NIDA,DIV CLIN RES,TREATMENT RES BRANCH,ROCKVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT COUNCIL ALCOHOL AND ADDITIONS PI LAUSANNE PA CASE POSTALE 140, CH-1001 LAUSANNE, SWITZERLAND PY 1992 BP 1558 EP 1559 PG 2 WC Substance Abuse SC Substance Abuse GA BC59Z UT WOS:A1992BC59Z00224 ER PT B AU NGUYEN, T BROWNELL, GL AF NGUYEN, T BROWNELL, GL BE Watson, EE Schlafkestelson, AT TI A MONTE-CARLO SIMULATION OF BORON NEUTRON-CAPTURE REACTIONS IN CELLS - MICRODOSIMETRIC ASPECTS SO 5TH INTERNATIONAL RADIOPHARMACEUTICAL DOSIMETRY SYMPOSIUM LA English DT Proceedings Paper CT 5th International Radiopharmaceutical Dosimetry Symposium CY MAY 07-10, 1991 CL OAK RIDGE, TN SP OAK RIDGE ASSOC UNIV, US FDA, US DOE C1 NIH,DEPT NUCL MED,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU US DEPT COMMERCE NATL TECH INFORMATION SERVICE PI WASHINGTON PA 14TH & CONSTITUTION AVE, WASHINGTON, DC 20230 PY 1992 BP 519 EP 530 PG 12 WC Oncology; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging GA BZ64A UT WOS:A1992BZ64A00042 ER PT J AU LENGVARI, I CSOKNYA, M MERCHENTHALER, I HAMORI, J AF LENGVARI, I CSOKNYA, M MERCHENTHALER, I HAMORI, J TI IMMUNOHISTOCHEMICAL STUDY OF THE NERVOUS-SYSTEM IN EARTHWORM (LUMBRICUS-TERRESTRIS L) SO ACTA BIOLOGICA HUNGARICA LA English DT Article; Proceedings Paper CT 7TH SYMP OF THE INTERNATIONAL SOC FOR INVERTEBRATE NEUROBIOLOGY CY JUN 23-28, 1991 CL TIHANY, HUNGARY SP INT SOC INVERBRATE NEUROBIOL DE NEUROPEPTIDES; CATECHOLAMINES; SEROTONIN; IMMUNOHISTOLOGY; EARTHWORM ID TISSUE FIXATION METHOD; IMMUNOCHEMICAL EVIDENCE; MICROWAVE IRRADIATION; IMMUNOREACTIVITY; PEPTIDE; IDENTIFICATION; CYTOCHEMISTRY; BRAIN AB In the present work it we describe serotonin, noradrenaline, proctolin, neuropeptide Y, substance P, and calcitonin gene related peptide immunoreactive structures in earthworm. A few large serotonin immunoreactive perikarya are located in brain and in the stomatograstric ganglia and many of them in the segmental ganglia. A serotonin immunoreactive fiber plexus can be seen beneath the epithelium of the body wall, both the sensory papillae and chaetae contain serotonin immunoreactive elements. Some of the sensory cells are serotonin immunoreactive, too. A serotonin immunoreactive network can ben found in the enteric network of the fore- and mid-gut. Only a few noradrenaline immunoreactive cells are observed in the caudal part of the brain, while their number in the segmental ganglia is high. Proctolin-, and substance P immunoreactive cells are small and numerous in the brain without any preference in their location. Such nerve cells are widely distributed in the ganglia of the stomatogastric system, in the subesophageal and in segmental ganglia. Many surface epithelial (probably sensory) cells are proctolin immunoreactive. Substance P immunoreactive nerve cells can also be located in the entire length of the enteric plexus together with substance P immunoreactive fibers. No neuropeptide Y- or calcitonin gene related peptide immunoreactive structures can be seen in the brain. A relative small number of neuropeptide Y- and calcitonin gene related peptide immunoreactive perikarya, and a rich network of neuropeptide Y- and calcitonin gene related peptide immunoreactive fibers can be detected in the subesophageal ganglion. According to preliminary studies, neuropeptide Y is probably co-localized with serotonin. C1 JANUS PANNONIUS UNIV,DEPT ZOOL,PECS,HUNGARY. NIH,DEPT HLTH & HUMAN SERV,RES TRIANGLE PK,NC 27703. RP LENGVARI, I (reprint author), UNIV PECS,DEPT ANAT,SZIGETI U 12,H-7643 PECS,HUNGARY. NR 16 TC 12 Z9 12 U1 2 U2 7 PU AKADEMIAI KIADO PI BUDAPEST PA PO BOX 245, H-1519 BUDAPEST, HUNGARY SN 0236-5383 J9 ACTA BIOL HUNG JI Acta Biol. Hung. PY 1992 VL 43 IS 1-4 BP 253 EP 258 PG 6 WC Biology SC Life Sciences & Biomedicine - Other Topics GA KT586 UT WOS:A1992KT58600024 PM 1299114 ER PT J AU FUJIMOTO, K DASILVA, PP AF FUJIMOTO, K DASILVA, PP TI FRACTURE-FLIP TRITON X-100 REVEALS THE CYTOPLASMIC SURFACE OF HUMAN ERYTHROCYTE-MEMBRANES SO ACTA HISTOCHEMICA ET CYTOCHEMICA LA English DT Article ID SKELETON; VISUALIZATION; ULTRASTRUCTURE AB We propose the use of fracture-flip combined with Triton X-100 extraction to visualize the cytoplasmic surface of plasma membranes. Unfixed human erythrocytes were freeze-fractured, carbon-cast, and thawed. The carbon casts, along with attached freeze-fractured erythrocytes, were treated with 2% Triton X-100 to solubilize unfractured plasma membranes and to release haemoglobin. After repeated washing, the carbon-casts, along with attached protoplasmic and exoplasmic membrane halves, were picked on grids, flipped, and Pt-shadowed. Our method leads to extended views of the cytoplasmic surface revealing the fibrillar network that laminates the inner surface of the erythrocyte membrane. Spectrin immunogold labelling of fractured, carbon cast erythrocytes shows that the colloidal gold particles are associated with the fibrillar network at the cytoplasmic surface. Removal of membrane skeletal elements including spectrin by treatment with a low ionic strength buffer containing EDTA leads to loss of the network and reveals globular particles on the cytoplasmic surface of the membrane. These globular particles contained band 3, as shown by immunogold labelling. Our method can be extended to both the ultrastructural observation and the cytochemistry of the cytoplasmic surfaces of other biomembranes. C1 NCI, MATH BIOL LAB, MEMBRANE BIOL SECT, FREDERICK, MD 21701 USA. NR 21 TC 5 Z9 5 U1 0 U2 0 PU JAPAN SOC HISTOCHEMISTRY & CYTOCHEMISTRY PI KYOTO PA C/O NAKANISHI PRINTING CO LTD, SHIMODACHIURI-OGAWA, KAMIGYO-KU, KYOTO, 602-8048, JAPAN SN 0044-5991 EI 1347-5800 J9 ACTA HISTOCHEM CYTOC JI Acta Histochem. Cytochem. PY 1992 VL 25 IS 1-2 BP 255 EP 264 PG 10 WC Cell Biology SC Cell Biology GA HU716 UT WOS:A1992HU71600038 ER PT J AU ROBBINS, J LAKSHMANAN, M AF ROBBINS, J LAKSHMANAN, M TI THE MOVEMENT OF THYROID-HORMONES IN THE CENTRAL-NERVOUS-SYSTEM SO ACTA MEDICA AUSTRIACA LA English DT Article; Proceedings Paper CT 4TH THYROID SYMP : BRAIN AND THYROID CY MAY 06-09, 1992 CL GRAZ, AUSTRIA SP STEIERMARK LANDESREGIER, ABT WISSENSCH & FORSCH, BOEHRINGER MANNHEIM, LEITNER COMP PARTNER, ELSCINT MED TECHNOL, FRIEB, HOFSTATTER, BENDER MED SYST, ABBOTT, ASSISTA DE THYROID HORMONE TRANSPORT; BLOOD BRAIN BARRIER; CHOROID PLEXUS; GLIAL CELLS; NEURONS ID CARRIER-MEDIATED TRANSPORT; BLOOD-BRAIN-BARRIER; CHOROID-PLEXUS; CEREBROSPINAL-FLUID; TRIIODOTHYRONINE TRANSPORT; TRANSTHYRETIN SYNTHESIS; THYROXINE TRANSPORT; RAT-BRAIN; PROTEIN; CELLS AB Thyroid hormones in the central nervous system (CNS) present a number of complexities which include a marked difference in hormone effects on the developing brain compared to the mature brain, extensive regional heterogeneity within the brain, and alternate ways by which the hormones gain entry to the CNS and its cells. Furthermore, most of the T3 found within brain cells is derived from the T4 that they have accumulated. This brief review concerns the movement of the thyroid hormones as they leave the bloodstream and make their way into and through the CNS. There are many sites for potential control of thyroid hormone transport into the central nervous system. The blood brain barrier and the choroid plexus may work in tandem as two parallel resistors subjected to different controls to maintain brain interstitial levels of thyroid hormone at near constant levels. Thyroid hormone may enter neurons directly from the interstitial fluid or indirectly from the glial cells. Nonetheless, both neurons, perhaps at the synaptosome, and glial cells are capable of transporting and concentrating thyroid hormones at physiological levels. C1 CASE WESTERN RESERVE UNIV,DEPT MED,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,DEPT PHYSIOL,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,DEPT BIOPHYS,CLEVELAND,OH 44106. RP ROBBINS, J (reprint author), NIH,GENET & BIOCHEM BRANCH,ENDOCRINOL SECT,BLDG 10,ROOM 8N315,BETHESDA,MD 20892, USA. NR 34 TC 17 Z9 17 U1 0 U2 0 PU BLACKWELL WISSENSCHAFTS-VERLAG GMBH PI BERLIN PA KURFURSTENDAMM 57, D-10707 BERLIN, GERMANY SN 0303-8173 J9 ACTA MED AUST JI Acta Med. Austriaca PY 1992 VL 19 SI 1 BP 21 EP 25 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA JG074 UT WOS:A1992JG07400006 PM 1519446 ER PT J AU GREWAL, RP MCLATCHEY, SK AF GREWAL, RP MCLATCHEY, SK TI CEREBROVASCULAR MANIFESTATIONS IN A FEMALE CARRIER OF FABRYS-DISEASE SO ACTA NEUROLOGICA BELGICA LA English DT Article DE FABRYS DISEASE; INHERITED DISORDER; STROKE AB A female carrier of Fabry's disease with neurological manifestations is presented. An elective ophthalmological examination revealed a whorl keratopathy suggesting that the patient may be a carrier of Fabry's disease. She subsequently suffered two brainstem ischemic events. Cranial MRI examination performed revealed evidence of multiple subcortical strokes and diffuse white matter disease in her frontal lobes. Biochemical analysis confirmed that this patient was a carrier of Fabry's disease. The cerebrovascular manifestations may be secondary to tissue variability of mutant enzyme activity. C1 NIMH, CLIN NEUROGENET BRANCH, BETHESDA, MD 20892 USA. NATL NAVAL MED CTR, BETHESDA, MD 20814 USA. NR 7 TC 16 Z9 17 U1 0 U2 0 PU ACTA MEDICA BELGICA PI BRUSSELS PA AVENUE CIRCULAIRE 138-A, B-1180 BRUSSELS, BELGIUM SN 0300-9009 J9 ACTA NEUROL BELG JI Acta Neurol. Belg. PY 1992 VL 92 IS 1 BP 36 EP 40 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA HH896 UT WOS:A1992HH89600005 PM 1546524 ER PT J AU PURDY, RH MOORE, PH MORROW, AL PAUL, SM AF PURDY, RH MOORE, PH MORROW, AL PAUL, SM TI NEUROSTEROIDS AND GABA(A) RECEPTOR FUNCTION SO ADVANCES IN BIOCHEMICAL PSYCHOPHARMACOLOGY LA English DT Review ID RAT-BRAIN; 3-ALPHA-HYDROXY-5-ALPHA-PREGNAN-20-ONE; METABOLISM; SECRETION; STEROIDS; CELLS C1 SW FDN BIOMED RES,DEPT ORGAN CHEM,SAN ANTONIO,TX 78228. UNIV N CAROLINA,SCH MED,CHAPEL HILL,NC 27599. NIMH,CLIN NEUROSCI BRANCH,MOLEC PHARMACOL SECT,BETHESDA,MD 20892. NR 18 TC 31 Z9 33 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0065-2229 J9 ADV BIOCHEM PSYCHOPH JI Adv. Biochem. Psychopharmacol. PY 1992 VL 47 BP 87 EP 92 PG 6 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA JB761 UT WOS:A1992JB76100009 PM 1354922 ER PT J AU MONTPIED, P PAUL, SM AF MONTPIED, P PAUL, SM TI STUDIES ON THE EXPRESSION OF GABA(A) RECEPTOR ALPHA-SUBUNIT MESSENGER-RNAS SO ADVANCES IN BIOCHEMICAL PSYCHOPHARMACOLOGY LA English DT Review ID DOWN-REGULATION; RAT; COMPLEX; BRAIN RP MONTPIED, P (reprint author), NIMH,CLIN NEUROSCI BRANCH,MOLEC PHARMACOL SECT,BLDG 10,ROOM 4N214,BETHESDA,MD 20892, USA. NR 14 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0065-2229 J9 ADV BIOCHEM PSYCHOPH JI Adv. Biochem. Psychopharmacol. PY 1992 VL 47 BP 301 EP 309 PG 9 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA JB761 UT WOS:A1992JB76100032 PM 1324580 ER PT J AU WEIGHT, FF AGUAYO, LG WHITE, G LOVINGER, DM PEOPLES, RW AF WEIGHT, FF AGUAYO, LG WHITE, G LOVINGER, DM PEOPLES, RW TI GABA-GATED AND GLUTAMATE-GATED ION CHANNELS AS MOLECULAR SITES OF ALCOHOL AND ANESTHETIC ACTION SO ADVANCES IN BIOCHEMICAL PSYCHOPHARMACOLOGY LA English DT Review ID ETHANOL INHIBITION; RAT; HIPPOCAMPAL; RELEASE; RECEPTORS; NEURONS; SLICES; CELLS; BRAIN RP WEIGHT, FF (reprint author), NIAAA, MOLEC & CELLULAR NEUROBIOL LAB, 12501 WASHINGTON AVE, ROCKVILLE, MD 20852 USA. NR 26 TC 59 Z9 60 U1 1 U2 6 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0065-2229 J9 ADV BIOCHEM PSYCHOPH JI Adv. Biochem. Psychopharmacol. PY 1992 VL 47 BP 335 EP 347 PG 13 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA JB761 UT WOS:A1992JB76100036 PM 1354918 ER PT J AU HEIDECKER, G KOLCH, W MORRISON, DK RAPP, UR AF HEIDECKER, G KOLCH, W MORRISON, DK RAPP, UR TI THE ROLE OF RAF-1 PHOSPHORYLATION IN SIGNAL-TRANSDUCTION SO ADVANCES IN CANCER RESEARCH LA English DT Review ID COLONY-STIMULATING FACTOR; COMPLETE CODING SEQUENCE; TYROSINE PROTEIN-KINASE; GAP-ASSOCIATED PROTEINS; PHOSPHOLIPASE-C-GAMMA; V-RAF; EGF RECEPTOR; A-RAF; RAPID PHOSPHORYLATION; CARRYING RETROVIRUS C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RP HEIDECKER, G (reprint author), NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,VIRAL PATHOL SECT,FREDERICK,MD 21702, USA. OI Kolch, Walter/0000-0001-5777-5016 NR 85 TC 125 Z9 126 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0065-230X J9 ADV CANCER RES JI Adv. Cancer Res. PY 1992 VL 58 BP 53 EP 73 DI 10.1016/S0065-230X(08)60290-0 PG 21 WC Oncology SC Oncology GA MC969 UT WOS:A1992MC96900003 PM 1312290 ER PT J AU BIESSMANN, H MASON, JM AF BIESSMANN, H MASON, JM TI GENETICS AND MOLECULAR-BIOLOGY OF TELOMERES SO ADVANCES IN GENETICS INCORPORATING MOLECULAR GENETIC MEDICINE LA English DT Review ID OXYTRICHA MACRONUCLEAR DNA; HUMAN SEX-CHROMOSOMES; AUTONOMOUSLY REPLICATING SEQUENCES; SUBTELOMERIC REPEAT SEQUENCES; TERMINAL TRANSFERASE-ACTIVITY; POSITION EFFECT VARIEGATION; HUNTINGTON DISEASE GENE; SALIVARY-GLAND NUCLEI; SACCHAROMYCES-CEREVISIAE; DROSOPHILA-MELANOGASTER C1 NIEHS,EXPTL CARCINOGENESIS & MUTAGENESIS BRANCH,RES TRIANGLE PK,NC 27709. RP BIESSMANN, H (reprint author), UNIV CALIF IRVINE,CTR DEV BIOL,IRVINE,CA 92717, USA. NR 306 TC 104 Z9 105 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0065-2660 J9 ADV GENET JI Adv. Genet. PY 1992 VL 30 BP 185 EP 249 DI 10.1016/S0065-2660(08)60321-1 PG 65 WC Genetics & Heredity SC Genetics & Heredity GA MC967 UT WOS:A1992MC96700005 PM 1456111 ER PT J AU YEWDELL, JW BENNINK, JR AF YEWDELL, JW BENNINK, JR TI CELL BIOLOGY OF ANTIGEN-PROCESSING AND PRESENTATION TO MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I MOLECULE-RESTRICTED T-LYMPHOCYTES SO ADVANCES IN IMMUNOLOGY LA English DT Review ID HLA CLASS-I; VACCINIA VIRUS ENCODES; BETA-2-MICROGLOBULIN TRANSLATED INVITRO; ENDOGENOUSLY SYNTHESIZED PEPTIDE; H-2-DEFICIENT LYMPHOMA VARIANTS; MATERNALLY TRANSMITTED ANTIGEN; PROTEASOME-RELATED GENE; MHC HEAVY-CHAINS; BREFELDIN-A; ENDOPLASMIC-RETICULUM RP YEWDELL, JW (reprint author), NIAID, VIRAL DIS LAB, BETHESDA, MD 20892 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 372 TC 384 Z9 386 U1 1 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0065-2776 J9 ADV IMMUNOL JI Adv. Immunol. PY 1992 VL 52 BP 1 EP 123 DI 10.1016/S0065-2776(08)60875-5 PG 123 WC Immunology SC Immunology GA MC110 UT WOS:A1992MC11000001 PM 1442305 ER PT J AU KINDT, TJ HIRSCH, VM JOHNSON, PR SAWASDIKOSOL, S AF KINDT, TJ HIRSCH, VM JOHNSON, PR SAWASDIKOSOL, S TI ANIMAL-MODELS FOR ACQUIRED-IMMUNODEFICIENCY-SYNDROME SO ADVANCES IN IMMUNOLOGY LA English DT Review ID FELINE LEUKEMIA-VIRUS; SCID-HU MOUSE; IMMUNE-DEFICIENCY SYNDROME; CHIMPANZEES PAN-TROGLODYTES; T-LYMPHOTROPIC LENTIVIRUS; SYNDROME FELV-FAIDS; RHESUS-MONKEYS; VACCINE PROTECTION; MOLECULAR-CLONING; MACAQUE MONKEYS C1 CHILDRENS HOSP RES FDN,COLUMBUS,OH 43205. RP KINDT, TJ (reprint author), NIAID,IMMUNOGENET LAB,TWINBROOK FACILITY 2,ROCKVILLE,MD 20852, USA. RI Johnson, Philip/A-6892-2009 NR 215 TC 45 Z9 45 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0065-2776 J9 ADV IMMUNOL JI Adv. Immunol. PY 1992 VL 52 BP 425 EP 474 DI 10.1016/S0065-2776(08)60880-9 PG 50 WC Immunology SC Immunology GA MC110 UT WOS:A1992MC11000006 PM 1442309 ER PT J AU KOLENBRANDER, PE LONDON, J AF KOLENBRANDER, PE LONDON, J TI ECOLOGICAL SIGNIFICANCE OF COAGGREGATION AMONG ORAL BACTERIA SO ADVANCES IN MICROBIAL ECOLOGY LA English DT Review ID SALIVA-COATED HYDROXYAPATITE; ACTINOMYCES-VISCOSUS T14V; BUCCAL EPITHELIAL-CELLS; CAPNOCYTOPHAGA-OCHRACEA ATCC-33596; BACTEROIDES-LOESCHEII PK1295; STREPTOCOCCUS-SANGUIS FW213; FIMBRIA-ASSOCIATED ADHESINS; GINGIVAL CREVICULAR FLUID; PROLINE-RICH PROTEINS; HUMAN DENTAL PLAQUE RP KOLENBRANDER, PE (reprint author), NIDR,MICROBIAL ECOL LAB,BETHESDA,MD 20892, USA. NR 170 TC 53 Z9 54 U1 0 U2 7 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0147-4863 J9 ADV MICROB ECOL JI Adv. Microb. Ecol. PY 1992 VL 12 BP 183 EP 217 PG 35 WC Ecology; Microbiology SC Environmental Sciences & Ecology; Microbiology GA KH214 UT WOS:A1992KH21400004 ER PT J AU KESSIN, RH FLEISCHMANN, RD GOTTESMAN, MM JASTORFF, B CAMPAGNE, MMV AF KESSIN, RH FLEISCHMANN, RD GOTTESMAN, MM JASTORFF, B CAMPAGNE, MMV TI USE OF THE YEAST LOW-KM CAMP-PHOSPHODIESTERASE GENE TO CONTROL CYCLIC-AMP LEVELS IN MAMMALIAN-CELLS SO ADVANCES IN SECOND MESSENGER AND PHOSPHOPROTEIN RESEARCH LA English DT Review ID DEPENDENT PROTEIN-KINASE; DICTYOSTELIUM-DISCOIDEUM; SACCHAROMYCES-CEREVISIAE; SIGNAL-TRANSDUCTION; TRANSCRIPTION; FORSKOLIN; CLONING C1 UNIV BREMEN,FACHBEREICH BIOL CHEM,INST ORGAN CHEM,W-2800 BREMEN,GERMANY. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. RP KESSIN, RH (reprint author), COLUMBIA UNIV,DEPT ANAT & CELL BIOL,NEW YORK,NY 10032, USA. FU NIAID NIH HHS [AI 24240] NR 28 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1040-7952 J9 ADV SEC MESS PHOSPH JI Adv. Second Messenger Phosphoprot. Res. PY 1992 VL 25 BP 13 EP 27 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GW632 UT WOS:A1992GW63200002 PM 1313255 ER PT J AU KINCAID, RL BALABAN, CD BILLINGSLEY, ML AF KINCAID, RL BALABAN, CD BILLINGSLEY, ML TI REGIONAL AND DEVELOPMENTAL EXPRESSION OF CALMODULIN-DEPENDENT CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE IN RAT-BRAIN SO ADVANCES IN SECOND MESSENGER AND PHOSPHOPROTEIN RESEARCH LA English DT Review ID PROTEIN; DICTYOSTELIUM; AMP; DIFFERENTIATION; LOCALIZATION; ACTIVATOR; NEURONS; ENZYMES; TISSUES; CELLS C1 UNIV PITTSBURGH,SCH MED,DEPT OTOLARYNGOL,PITTSBURGH,PA 15213. UNIV PITTSBURGH,SCH MED,DEPT NEUROBIOL,PITTSBURGH,PA 15213. UNIV PITTSBURGH,SCH MED,DEPT ANAT,PITTSBURGH,PA 15213. UNIV PITTSBURGH,SCH MED,DEPT CELL SCI,PITTSBURGH,PA 15213. UNIV PITTSBURGH,SCH MED,CTR NEUROSCI,INST EYE & EAR,PITTSBURGH,PA 15213. PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT PHARMACOL,HERSHEY,PA 17033. PENN STATE UNIV,MILTON S HERSHEY MED CTR,CTR CELL & MOLEC BIOL,HERSHEY,PA 17033. RP KINCAID, RL (reprint author), NIAAA,ALCOHOL DRUG ABUSE & MENTAL HLTH ADM,IMMUNOL SECT,ROCKVILLE,MD 20852, USA. OI Balaban, Carey/0000-0002-3570-3844 FU NIA NIH HHS [R01 AG06377]; NINDS NIH HHS [K04 NS00891, R01 NS19850] NR 29 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1040-7952 J9 ADV SEC MESS PHOSPH JI Adv. Second Messenger Phosphoprot. Res. PY 1992 VL 25 BP 111 EP 122 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GW632 UT WOS:A1992GW63200009 PM 1313253 ER PT J AU MANGANIELLO, VC DEGERMAN, E SMITH, CJ VASTA, V TORNQVIST, H BELFRAGE, P AF MANGANIELLO, VC DEGERMAN, E SMITH, CJ VASTA, V TORNQVIST, H BELFRAGE, P TI MECHANISMS FOR ACTIVATION OF THE RAT ADIPOCYTE PARTICULATE CYCLIC-GMP-INHIBITED CYCLIC-AMP PHOSPHODIESTERASE AND ITS IMPORTANCE IN THE ANTILIPOLYTIC ACTION OF INSULIN SO ADVANCES IN SECOND MESSENGER AND PHOSPHOPROTEIN RESEARCH LA English DT Review ID KM CAMP PHOSPHODIESTERASE; DEPENDENT PROTEIN-KINASE; HORMONE-SENSITIVE LIPASE; HEPATIC PLASMA-MEMBRANES; FAT-CELLS; NUCLEOTIDE PHOSPHODIESTERASE; ADIPOSE-TISSUE; ADENYLATE-CYCLASE; LIPOLYTIC HORMONES; ADENOSINE 3' C1 UNIV LUND,DEPT MED & PHYSIOL CHEM,S-22100 LUND,SWEDEN. UNIV FLORENCE,DEPT BIOCHEM,I-50121 FLORENCE,ITALY. RP MANGANIELLO, VC (reprint author), NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892, USA. NR 83 TC 22 Z9 22 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1040-7952 J9 ADV SEC MESS PHOSPH JI Adv. Second Messenger Phosphoprot. Res. PY 1992 VL 25 BP 147 EP 164 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GW632 UT WOS:A1992GW63200012 PM 1313257 ER PT J AU HATFIELD, DL LEVIN, JG REIN, A OROSZLAN, S AF HATFIELD, DL LEVIN, JG REIN, A OROSZLAN, S TI TRANSLATIONAL SUPPRESSION IN RETROVIRAL GENE-EXPRESSION SO ADVANCES IN VIRUS RESEARCH LA English DT Review ID MURINE LEUKEMIA-VIRUS; COMPLETE NUCLEOTIDE-SEQUENCE; TOBACCO MOSAIC-VIRUS; MAMMARY-TUMOR VIRUS; ROUS-SARCOMA VIRUS; GAG-POL REGION; RIBOSOMAL FRAMESHIFTING SIGNAL; SIMIAN IMMUNODEFICIENCY VIRUS; YEAST RETROTRANSPOSON TY; BABOON ENDOGENOUS VIRUS C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,MOLEC VIROL & CARCINOGENESIS,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RP HATFIELD, DL (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CO-74101] NR 172 TC 111 Z9 136 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0065-3527 J9 ADV VIRUS RES JI Adv. Virus Res. PY 1992 VL 41 BP 193 EP 239 DI 10.1016/S0065-3527(08)60037-8 PG 47 WC Virology SC Virology GA MD550 UT WOS:A1992MD55000004 PM 1575083 ER PT J AU HILAKIVICLARKE, LA LISTER, RG AF HILAKIVICLARKE, LA LISTER, RG TI THE ROLE OF BODY-WEIGHT IN RESIDENT-INTRUDER AGGRESSION SO AGGRESSIVE BEHAVIOR LA English DT Article DE AGGRESSION; ETHANOL; MOUSE; RESIDENT-INTRUDER TEST ID SOCIAL-BEHAVIOR; MICE; ETHANOL; TESTS AB The behavior of male NIH Swiss mice of various body weights in the resident-intruder test of aggression was investigated. Mice were housed individually for 10 days prior to the test, and allocated to six groups. In the first three groups body weights of residents and group-housed intruders were matched, and the animals were divided into light, average, or heavy groups. In the last three groups weights of the intruder mice were either matched with the residents, or intruders were lighter or heavier than the residents. We found that light residents spent significantly less time in aggressive behaviors and longer time in defensive behaviors than the other two groups. The heavy mice showed most social investigation. The body weights of intruders were also shown to affect the behavior in the test: those residents which had light opponents spent a longer time in aggressive behavior than those which had matched or heavy opponents. The resident mice with heavy opponents showed most defensive behaviors. To study whether pharmacological manipulation may have different effects on behavior in the resident-intruder test in mice having different weights, animals of light, average, and heavy body weight received a low dose (0.8 g/kg) of ethanol 30 min prior to the test. We did not note any effect of ethanol on aggressive behavior in the three groups. The results suggest that body weight plays a significant role in determining the level of aggression and defensive behaviors in the resident-intruder test. RP HILAKIVICLARKE, LA (reprint author), NIAAA,DICBR,BLDG 10,ROOM 3C102,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 20 TC 8 Z9 8 U1 1 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0096-140X J9 AGGRESSIVE BEHAV JI Aggressive Behav. PY 1992 VL 18 IS 4 BP 281 EP 287 DI 10.1002/1098-2337(1992)18:4<281::AID-AB2480180404>3.0.CO;2-2 PG 7 WC Behavioral Sciences; Psychology, Multidisciplinary SC Behavioral Sciences; Psychology GA HZ211 UT WOS:A1992HZ21100003 ER PT S AU FORNACE, AJ JACKMAN, J HOLLANDER, MC HOFFMANLIEBERMANN, B LIEBERMANN, DA AF FORNACE, AJ JACKMAN, J HOLLANDER, MC HOFFMANLIEBERMANN, B LIEBERMANN, DA BE Franceschi, C Crepaldi, G Cristofalo, VJ Vijg, J TI GENOTOXIC-STRESS-RESPONSE GENES AND GROWTH-ARREST GENES - GADD, MYD, AND OTHER GENES INDUCED BY TREATMENTS ELICITING GROWTH ARREST SO AGING AND CELLULAR DEFENSE MECHANISMS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Proceedings Paper CT CONF ON AGING AND CELLULAR DEFENSE MECHANISMS CY SEP 22-26, 1991 CL MODENA, ITALY SP NEW YORK ACAD SCI, NIA, SIGMA TAU, EURAGE RP FORNACE, AJ (reprint author), NCI,DTP,MOLEC PHARMACOL LAB,ROOM 5C09,BLDG 37,BETHESDA,MD 20892, USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 0 TC 156 Z9 156 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA NEW YORK SN 0077-8923 BN 0-89766-729-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1992 VL 663 BP 139 EP 153 DI 10.1111/j.1749-6632.1992.tb38657.x PG 15 WC Geriatrics & Gerontology; Immunology; Physiology SC Geriatrics & Gerontology; Immunology; Physiology GA BX33J UT WOS:A1992BX33J00016 PM 1482047 ER PT J AU KLINMAN, DM KRIEG, A CONOVER, J USSERY, MA BLACK, PL AF KLINMAN, DM KRIEG, A CONOVER, J USSERY, MA BLACK, PL TI EFFECT OF CYCLOPHOSPHAMIDE, TOTAL-BODY IRRADIATION, AND ZIDOVUDINE ON RETROVIRUS PROLIFERATION AND DISEASE PROGRESSION IN MURINE AIDS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID BONE-MARROW TRANSPLANTATION; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; B-CELL ACTIVATION; LEUKEMIA VIRUSES; C57BL/6 MICE; T-CELLS; INDUCTION; INFECTION; ASSAY; ABNORMALITIES AB Murine acquired immunodeficiency syndrome (MAIDS) develops when C57Bl/6 mice are inoculated with LP-BM5 murine leukemia viruses. Disease progression in these animals is characterized by lymphadenopathy, polyclonal B-cell activation, severe immunodeficiency, and death. Mice with MAIDS have been used to examine the efficacy of antiretroviral therapies for possible use in AIDS patients. In the present work, MAIDS mice were employed to test the hypothesis that established retroviral infection might be cured by the combined use of a cytotoxic agent (cyclophosphamide) and total body irradiation-a regimen reported to have successfully cured HIV-1 infection in one AIDS patient. Results indicate that the ablation of retrovirus-infected lymphoid cells reduced but did not eliminate LP-BM5 infection. Moreover, this regimen was no more effective at controlling virus proliferation or preventing the polyclonal IgG activation characteristic of murine AIDS than was AZT alone. C1 US FDA,CDER,DIV ANTIVIRAL DRUG PROD,ROCKVILLE,MD 20857. NIAMS,CELLULAR IMMUNOL SECT,BETHESDA,MD. SO RES INST,FCR,GAITHERSBURG,MD. RP KLINMAN, DM (reprint author), US FDA,CBER,RETROVIRUS RES LAB,BLDG 29A,ROOM 3 D02,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [1U01AI25617-01] NR 38 TC 7 Z9 7 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 JAN PY 1992 VL 8 IS 1 BP 101 EP 106 DI 10.1089/aid.1992.8.101 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA GZ934 UT WOS:A1992GZ93400013 PM 1310603 ER PT J AU SHEFFER, AL BOUSQUET, J BUSSE, WW CLARK, TJH DAHL, R EVANS, D FABBRI, LM HARGREAVE, FE HOLGATE, ST LENFANT, C HURD, SS TAGGARRT, VS FULWOOD, R MAGNUSSEN, H PARTRIDGE, MR PAUWELS, R RODRIGUEZROISIN, R RUBINFELD, A SOTES, MR SEARS, MR SZCZEKLIK, A WARNER, J AF SHEFFER, AL BOUSQUET, J BUSSE, WW CLARK, TJH DAHL, R EVANS, D FABBRI, LM HARGREAVE, FE HOLGATE, ST LENFANT, C HURD, SS TAGGARRT, VS FULWOOD, R MAGNUSSEN, H PARTRIDGE, MR PAUWELS, R RODRIGUEZROISIN, R RUBINFELD, A SOTES, MR SEARS, MR SZCZEKLIK, A WARNER, J TI INTERNATIONAL CONSENSUS REPORT ON DIAGNOSIS AND MANAGEMENT OF ASTHMA SO ALLERGY LA English DT Review ID AIR-FLOW OBSTRUCTION; BRONCHIAL-ASTHMA; DOUBLE-BLIND; INHALED CORTICOSTEROIDS; NEDOCROMIL SODIUM; SELF-MANAGEMENT; ADULT ASTHMA; BECLOMETHASONE DIPROPIONATE; SYMPATHOMIMETIC TREATMENT; BRONCHOALVEOLAR LAVAGE AB Asthma is a chronic, persistent inflammatory disease of the airways characterized by exacerbations of coughing, wheezing, chest tightness, and difficult breathing that are usually reversible, but that can be severe and sometimes fatal. The major factors contributing to asthma morbidity and mortality are underdiagnosis and inappropriate treatments. Most exacerbations reflect a treatment failure because they can be prevented if treatment of the disease is comprehensive and ongoing. The goals of asthma therapy are to improve the patient's quality of live by achieving and maintaining control of syptoms; preventing exacerbations; attaining normal lung function; maintaining normal activity levels, including exercise; and avoiding adverse effects from asthma medications. Recent studies have revealed thet inflammation is a critical feature in the pathogenesis of asthma, and therefore asthma therapy is predicated on medications to reverse and prevent this abnormality. Anti-inflammatory medications such as inhaled corticosteroids, sodium cromoglycate, and nedocromil are the primary therapy for the chronic care of all but mild, intermittent asthma. Further, early introduction or an increase in the dose of corticosteroids is an important component of treating severe exacerbations in order to speed resolutio of the exacerbation and prevent rucurrence. A six-part asthma management program is recommended for effective treatment: 1. Educate patients to develop a partnership in asthma management. Open communication, joint development of a treatment plan by the clinician and patient (guided self-management strategies), and encouragement of th efamily's efforts to improve asthma management will help patients gain the motivation, skill, and confidence to control their asthma. 2. Assess and monitor asthma severity with measures of lung function. Spirometry is recommended for the initial and scheduled periodic assessements of all asthma patients.A period of home peak flow monitoring may be useful for the initial assessement. Spirometry or peak expiratory flow monitoring is essential in hospital-based management of exacerbations. Home peak expiratory flow monitoring should be considered for patients who take medications daily. 3. Avoid or control asthma triggers. Environmental control measures are an important prevention strategy: Appropriate avoidance of triggers may reduce symptoms, the need for medication, and levels of nonspecific airway hyperresponsiveness. The role of specific immunotherapy in asthma management is under continual investigation. Currently available asthma management strategies with patient education, avoidance measures, and pharmacologic treatment usually provide good control of asthma. Immunotherapy may be considered when avoiding allergens is not possible, when appropriate medications fail to control symptoms, and where an effective specific immunotherapy is available. 4. Establish medication plans for chronic management. Because asthma is a dynamic as well as a chronic conditio, medication plans need to accomodate variability among patients as well as within individual patients over time. A stepwise approach to pharmacology therapy, in which the number and frequency of medications are increased with increasing classification of asthma severity, permits this flexibility. Once control of asthma is sustained for several weeks or months, a reduction in therapy - a step down - can be carefully considered and is needed to identify the minimum therapy required to maintain control. The four steps to achieve and maintain control of asthma emphasize that anything more than mild occasional asthma requires daily therapy with anti-inflammatory agents and that patients should not rely on frequent use of bronchodilator agents to control their asthma. Figure 4 in Chapter 2 summarizes the treatment recommended in the stepwise approach. A color-coded asthma zone management system for patients has been developed to help patients understand and monitor the variable nature of this chronic disease. and take appropriate actions to maintain control of asthma. The forst (Green Zone) reflects therapy required to achieve the goals of therapy, i.e., maintaint control of symptoms and prevent exacerbations. The stepwise approach described above is used to identify the minimum amount of medication required to maintain control of the patient's asthma. The second (Yellow Zone) reflects a deterioration in asthma control and indicates a need to temporarily increase treatments as well as a need to review the Green Zone plan. The third (Red ZOne) signals a medical alert, and immediate steps to amnage the exacerbation are required, with subsequent adjustment of the Green Zone plan. Written plans for each zone are essential to improve patient adherence. 5. Establish plans for managing exacerbations. Exacerbations usually reflect either a failure of chronic management or exposure to a noxious agent. Severe exacerbations often reflect inadequate action at the onset of the exacerbation. Therapy for exacerbations emphasizes the early introduction of corticosteroids as well as frequent administration of inhaled beta2-agonists. Patients need a written plan for recognizing signs that asthma is worsening, for when, how, and for how long to increase treatment, and for reaching medical care. 6. Provide regular followup care. Patients need regular supervision and support by a clinician who is knowledgeable about asthma. Continual monitoring is essential to assure that therapeutic goals are met. The following report elaborates upon each of these six parts of effective asthma management. It provides more detailed recommendations and documentation from the scientific literature. C1 UNIV MONTPELLIER 1,F-34060 MONTPELLIER,FRANCE. UNIV WISCONSIN,SCH MED,MADISON,WI 53706. NATL HEART & LUNG INST,LONDON,ENGLAND. AARHUS UNIV HOSP,DK-8000 AARHUS,DENMARK. COLUMBIA UNIV,NEW YORK,NY 10027. UNIV FERRARA,I-44100 FERRARA,ITALY. MCMASTER UNIV,HAMILTON L8S 4L8,ONTARIO,CANADA. SOUTHAMPTON GEN HOSP,SOUTHAMPTON SO9 4XY,HANTS,ENGLAND. NHLBI,BETHESDA,MD 20892. KRANKENHAUS GROSSHANSDORF,GROSSHANSDORF,GERMANY. WHIPPS CROSS HOSP & CHEST CLIN,LONDON,ENGLAND. STATE UNIV GHENT HOSP,B-9000 GHENT,BELGIUM. HOSP CLIN BARCELONA,BARCELONA,SPAIN. ROYAL MELBOURNE HOSP,PARKVILLE,VIC 3050,AUSTRALIA. CTR UNIV SALUD PUBL,MADRID,SPAIN. NICHOLAS COPERNICUS MED ACAD,PL-31501 KRAKOW,POLAND. RP SHEFFER, AL (reprint author), HARVARD UNIV,SCH MED,BOSTON,MA 02115, USA. RI Dahl, Ronahl/F-8170-2013; Fabbri, Leonardo/I-4055-2012 OI Fabbri, Leonardo/0000-0001-8894-1689 NR 137 TC 1 Z9 1 U1 0 U2 6 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-4538 J9 ALLERGY JI Allergy PY 1992 VL 47 IS 13 SU S BP R1 EP & PG 0 WC Allergy; Immunology SC Allergy; Immunology GA JA180 UT WOS:A1992JA18000001 ER PT J AU COHEN, SG EVANS, R AF COHEN, SG EVANS, R TI ASTHMA, ALLERGY AND IMMUNOTHERAPY - A HISTORICAL REVIEW .2. SO ALLERGY PROCEEDINGS LA English DT Review RP COHEN, SG (reprint author), NIAID,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 JAN-FEB PY 1992 VL 13 IS 1 BP 47 EP 58 DI 10.2500/108854192778878999 PG 12 WC Allergy SC Allergy GA HG190 UT WOS:A1992HG19000009 PM 1577265 ER PT J AU HORM, JW BURHANSSTIPANOV, L AF HORM, JW BURHANSSTIPANOV, L TI CANCER INCIDENCE, SURVIVAL, AND MORTALITY AMONG AMERICAN-INDIANS AND ALASKA NATIVES SO AMERICAN INDIAN CULTURE AND RESEARCH JOURNAL LA English DT Article ID CARCINOMA C1 NATL CANCER INST,SPECIAL POPULATIONS STUDIES BRANCH,ROCKVILLE,MD. RP HORM, JW (reprint author), NATL CTR HLTH STAT,HYATTSVILLE,MD 20782, USA. NR 15 TC 10 Z9 10 U1 0 U2 0 PU U C L A, AMER INDIAN STUDIES CENTER PI LOS ANGELES PA 3220 CAMPBELL HALL, BOX 951548, LOS ANGELES, CA 90095-1548 SN 0161-6463 J9 AM INDIAN CULT RES J JI Am. Indian Cult. Res. J. PY 1992 VL 16 IS 3 BP 21 EP 40 PG 20 WC History SC History GA KA195 UT WOS:A1992KA19500003 ER PT J AU RUOCCO, NA RING, ME HOLUBKOV, R JACOBS, AK DETRE, KM FAXON, DP FAXON, DP KELLETT, MA SANBORN, T JACOBS, AK ERARIO, M KING, SB DOUGLAS, J SUTOR, C KENT, KM EWELS, C KEHOE, K BLOCK, PC BLOCK, E HOLMES, DR VLIETSTRA, RE REEDER, GS BRESNAHAN, JF BRESNAHAN, DR BOVE, AA VONHAMMES, L BREVIG, S ALBASSEM, M LANCE, D BENTIVOGLIO, LG SHAPPELL, E COWLEY, MJ VETROVEC, GW LEWIS, SA DISCIASCIO, G KELLY, K GOSSELIN, AJ SWAYE, PS VIGNOLA, PA YON, H BOURASSA, MG DAVID, PR LABBE, M FAILLE, C CANNON, RO LEON, M MINCEMOYER, R MYLER, RK STERTZER, SH CLARK, DA MURPHY, M WILLIAMS, DO EMIN, S GALICHIA, JP MEIRES, J LEATHERMAN, LL SPRINGER, AJ MATTIES, J DORROS, G JANKEMATHIAK, L ENGEL, M DETRE, KM KELSEY, SF WILSON, J HOLUBKOV, R STEENKISTE, AR AMOROSO, W ELLIOTT, H NEIDERMEYER, V SWANSON, P ZONA, J GIBBONS, D WOLK, R ROBERTSON, T AF RUOCCO, NA RING, ME HOLUBKOV, R JACOBS, AK DETRE, KM FAXON, DP FAXON, DP KELLETT, MA SANBORN, T JACOBS, AK ERARIO, M KING, SB DOUGLAS, J SUTOR, C KENT, KM EWELS, C KEHOE, K BLOCK, PC BLOCK, E HOLMES, DR VLIETSTRA, RE REEDER, GS BRESNAHAN, JF BRESNAHAN, DR BOVE, AA VONHAMMES, L BREVIG, S ALBASSEM, M LANCE, D BENTIVOGLIO, LG SHAPPELL, E COWLEY, MJ VETROVEC, GW LEWIS, SA DISCIASCIO, G KELLY, K GOSSELIN, AJ SWAYE, PS VIGNOLA, PA YON, H BOURASSA, MG DAVID, PR LABBE, M FAILLE, C CANNON, RO LEON, M MINCEMOYER, R MYLER, RK STERTZER, SH CLARK, DA MURPHY, M WILLIAMS, DO EMIN, S GALICHIA, JP MEIRES, J LEATHERMAN, LL SPRINGER, AJ MATTIES, J DORROS, G JANKEMATHIAK, L ENGEL, M DETRE, KM KELSEY, SF WILSON, J HOLUBKOV, R STEENKISTE, AR AMOROSO, W ELLIOTT, H NEIDERMEYER, V SWANSON, P ZONA, J GIBBONS, D WOLK, R ROBERTSON, T TI RESULTS OF CORONARY ANGIOPLASTY OF CHRONIC TOTAL OCCLUSIONS (THE NATIONAL-HEART,-LUNG,-AND-BLOOD-INSTITUTE 1985-1986 PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY REGISTRY) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID BLOOD-INSTITUTE REGISTRY; ARTERY OCCLUSION; TERM AB There has been increasing application of coronary angioplasty to patients with chronic total occlusions. The acute and long-term outcome in 271 patients after coronary angioplasty (142 single and 129 multiple stenoses) of a total occlusion was compared with 1,429 patients undergoing angioplasty of subtotal (less-than-or-equal-to 99% stenosis) occlusions (885 single and 544 multilesion) participating in the 1985-1986 National Heart, Lung, and Blood Institute Percutaneous Transluminal Coronary Angioplasty Registry. Baseline characteristics were similar for each lesion group except for a higher incidence of prior myocardial infarction and left ventricular dysfunction (ejection fraction < 50%) in patients with total occlusion. Major complications (death, myocardial infarction or emergency bypass surgery) were similar (p = not significant) between patients with total and subtotal occlusions for single (6 vs 7%) and multilesion angioplasty (9 vs 6%). At 2 years, after making adjustments for baseline variables, patients with a total occlusion had a significantly increased risk of death compared with those with subtotal occlusion. There were no significant differences in cumulative event rates for myocardial infarction or bypass surgery. Approximately three-fourths of patients in each group were free of angina at 2 years. In conclusion, angioplasty of chronic total occlusions is associated with a similar acute complication rate. Despite similar relief of anginal symptoms, patients in the total occlusion group have a higher 2-year mortality. C1 BOSTON UNIV HOSP,MED CTR,BOSTON,MA 02218. EMORY UNIV HOSP,ATLANTA,GA 30322. GEORGETOWN UNIV HOSP,WASHINGTON,DC 20007. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. MED CTR HOSP,HOUSTON,TX. MED COLL PENN,PHILADELPHIA,PA 19129. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,RICHMOND,VA 23298. MIAMI HEART INST,MIAMI BEACH,FL 33140. MONTREAL HEART INST,MONTREAL H1T 1C8,QUEBEC,CANADA. NHLBI,BETHESDA,MD 20892. SETON MED CTR,DALY CITY,CA. BROWN UNIV,RHODE ISL HOSP,PROVIDENCE,RI 02903. ST FRANCIS REG MED CTR,WICHITA,KS 67214. ST LUKES EPISCOPAL HOSP,HOUSTON,TX 77030. ST LUKES HOSP,MILWAUKEE,WI 53215. UNIV PITTSBURGH,PITTSBURGH,PA 15260. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT EPIDEMIOL,PITTSBURGH,PA 15260. BOSTON UNIV HOSP,DEPT MED,BOSTON,MA. RP RUOCCO, NA (reprint author), BOSTON UNIV HOSP,MED CTR,EVAND MEM DEPT CLIN RES,CARDIOL SECT,88 E NEWTON ST,BOSTON,MA 02118, USA. FU NHLBI NIH HHS [HL-33292] NR 16 TC 70 Z9 76 U1 0 U2 3 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 1 PY 1992 VL 69 IS 1 BP 69 EP 76 DI 10.1016/0002-9149(92)90678-R PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA GY225 UT WOS:A1992GY22500012 PM 1729870 ER PT J AU RAVUSSIN, E BOGARDUS, C AF RAVUSSIN, E BOGARDUS, C TI A BRIEF OVERVIEW OF HUMAN ENERGY-METABOLISM AND ITS RELATIONSHIP TO ESSENTIAL OBESITY SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE INDIRECT CALORIMETRY; BODY COMPOSITION; PIMA INDIANS ID EXPENDITURE; TWINS; EXERCISE; RISK AB Twenty-four hour energy expenditure (24EE) can be measured in a respiratory chamber. 24EE is comprised of the basal metabolic rate, the thermic effect of food, and the energy cost of physical activity. The major determinant of 24EE, fat-free mass, accounts for approximately 80% of the variance observed between individuals. Genetic factors seem to be the cause of the familial aggregation of 24EE in man. The variability of 24EE for a given body size and composition is of importance because a low metabolic rate is a major risk factor for weight gain in man. There is increasing evidence that obesity, often an inherited disorder, cannot always be attributed to gluttony and sloth. Similar to the need to treat essential hypertension, there is a need to treat a disorder perhaps best called essential obesity. RP NIDDKD, CLIN DIABET & NUTR SECT, PHOENIX, AZ 85016 USA. NR 12 TC 7 Z9 7 U1 0 U2 3 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JAN PY 1992 VL 55 IS 1 SU S BP 242 EP 245 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA GY611 UT WOS:A1992GY61100020 ER PT J AU MEDEIROS, LJ WEISS, LM AF MEDEIROS, LJ WEISS, LM TI NEW DEVELOPMENTS IN THE PATHOLOGICAL DIAGNOSIS OF ADRENAL-CORTICAL NEOPLASMS - A REVIEW SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Review DE ADRENAL CORTICAL NEOPLASMS; HISTOLOGIC DIAGNOSIS; PROGNOSTIC INDICATORS; IMMUNOHISTOCHEMISTRY; DNA CONTENT ANALYSIS; MOLECULAR GENETICS ID FLOW CYTOMETRIC ANALYSIS; DEOXYRIBONUCLEIC-ACID PLOIDY; WIEDEMANN-BECKWITH SYNDROME; RENAL-CELL CARCINOMA; ADRENOCORTICAL CARCINOMA; PROGNOSTIC-SIGNIFICANCE; TUMORS; DNA; CORTEX; EXPRESSION AB In the past decade, our knowledge of neoplasms arising in the adrenal cortex has been expanded greatly. Histologic criteria for distinguishing benign from malignant adrenal cortical neoplasms have been developed. In this review, three systems useful in making this distinction are reviewed and compared. Pathologic indicators of prognosis for adrenal cortical carcinomas have been proposed and these include mitotic rate, stage, surgical resectability, nuclear grade, and tumor size. Of these, mitotic rate appears to be the best indicator. Adrenal cortical carcinomas with a high mitotic rate behave most aggressively. The role of immunohistochemical and DNA content analysis in the diagnosis of adrenal cortical neoplasms is limited. Neoplastic adrenal cortical cells contain a low density of keratins that is often destroyed by routine fixation and paraffin embedding. Thus, the absence of keratins in adrenal cortical neoplasms, particularly carcinomas, in routinely processed tissue should not dissuade the pathologist from making the diagnosis of an epithelial neoplasm. DNA content analysis has revealed an imperfect correlation between DNA ploidy and histologic diagnosis. Some adrenal cortical adenomas contain aneuploid stem cell lines, whereas some adrenal cortical carcinomas have diploid DNA content. Molecular genetic analyses suggest that one or more tumor suppressor genes may be involved in the pathogenesis of adrenal cortical neoplasms. C1 CITY HOPE NATL MED CTR,DEPT PATHOL,DUARTE,CA 91010. RP MEDEIROS, LJ (reprint author), NCI,PATHOL LAB,BLDG 10,ROOM 2N108,BETHESDA,MD 20892, USA. NR 74 TC 79 Z9 82 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JAN PY 1992 VL 97 IS 1 BP 73 EP 83 PG 11 WC Pathology SC Pathology GA GZ463 UT WOS:A1992GZ46300013 PM 1728867 ER PT J AU STEEL, E HAVERKOS, HW AF STEEL, E HAVERKOS, HW TI EPIDEMIOLOGIC STUDIES OF HIV AIDS AND DRUG-ABUSE SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; SAN-FRANCISCO; INFECTION; USERS; VIRUS AB The HIV and drug abuse epidemics are intertwined, and drug abusers make up a significant proportion of reported AIDS patients. For a variety of reasons, it is difficult to collect and interpret data about each epidemic. It is even more difficult to determine the relationships between the two. In this paper, various epidemiologic studies in both fields are reviewed. Some strengths and limitations of those studies are discussed, and possible methods for improvement are identified. C1 NIDA,DIV CLIN RES,ROCKVILLE,MD. RP STEEL, E (reprint author), NIDA,AIDS COORDINATING OFF,PARKLAWN BLDG,ROOM 10A38,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 17 TC 15 Z9 15 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0095-2990 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PY 1992 VL 18 IS 2 BP 167 EP 175 DI 10.3109/00952999208992829 PG 9 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA HN723 UT WOS:A1992HN72300005 PM 1562014 ER PT J AU BATTJES, RJ LEUKEFELD, CG PICKENS, RW AF BATTJES, RJ LEUKEFELD, CG PICKENS, RW TI AGE AT 1ST INJECTION AND HIV RISK AMONG INTRAVENOUS-DRUG-USERS SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article AB The relationship of age at first injection and HIV risk was explored in a nonblinded HIV seroprevalence study of intravenous drug users (IVDUs) admitted to methadone treatment in seven United States cities between February 1987 and June 1989. Comparisons were made of IVDUs who began injecting as adolescents, young adults, and adults in terms of drug use and sexual HIV risk behaviors and HIV serostatus. Early injectors consistently reported higher levels of drug-using risk behaviors (e.g., frequency of injection, frequency of needle sharing, and use of shooting galleries), and were more likely to be HIV seropositive. Among females, early injectors were also more likely to report sexual risk behaviors (e.g., multiple sex partners, prostitution). The relationship of age at first injection with selected risk behaviors and HIV serostatus was independent of subjects' age at interview, gender, and race/ethnicity. This study suggests that adolescent injectors are an important target group for HIV prevention efforts. C1 UNIV KENTUCKY,MULTIDISCIPLINARY RES CTR DRUG & ALCOHOL ABUSE,LEXINGTON,KY 40506. NIDA,ADDICT RES CTR,BALTIMORE,MD. RP BATTJES, RJ (reprint author), NIDA,DIV CLIN RES,ROCKVILLE,MD 20892, USA. NR 6 TC 56 Z9 56 U1 1 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0095-2990 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PY 1992 VL 18 IS 3 BP 263 EP 273 DI 10.3109/00952999209026066 PG 11 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA JF818 UT WOS:A1992JF81800003 PM 1415084 ER PT J AU ASHERY, RS MCAULIFFE, WE AF ASHERY, RS MCAULIFFE, WE TI IMPLEMENTATION ISSUES AND TECHNIQUES IN RANDOMIZED TRIALS OF OUTPATIENT PSYCHOSOCIAL TREATMENTS FOR DRUG-ABUSERS - RECRUITMENT OF SUBJECTS SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article ID TERM INTERPERSONAL PSYCHOTHERAPY; MAINTAINED OPIATE ADDICTS; CONDUCTING FAMILY-THERAPY; FOLLOW-UP; METHADONE-MAINTENANCE; METHODOLOGICAL ISSUES; CLINICAL-TRIALS; ONE-PERSON; PHARMACOTHERAPY; INTERVENTION AB We reviewed nine randomized clinical trials of outpatient psychosocial treatments for drug abuse to ascertain implementation problems and solution that the researchers developed. The most common problem was subject recruitment. Inadequate recruitment can disrupt a project's timetable, preoccupy its staff, reduce the trial's ability to detect treatment differences, and perhaps result in the trial's abandonment. The causes of recruitment problems include the need for large samples and multiple eligibility criteria, subject reluctance to be a "guinea pig," low client treatment motivation, client dislike of research procedures, clinicians' distrust of research, and difficulties collaborating with treatment agencies. Solutions include realistic assessment of the target population's size, use of mass media, statistical adjustments to minimize unnecessary sample exclusions, variable treatment assignment ratios, and prevention of common collaboration difficulties. C1 HARVARD UNIV,CAMBRIDGE HOSP,SCH MED,DEPT PSYCHIAT,CAMBRIDGE,MA 02139. RP ASHERY, RS (reprint author), NIDA,5600 FISHERS LANE,ROOM 9A-30,ROCKVILLE,MD 20857, USA. FU NIDA NIH HHS [DA02798, DA03075, DA04418] NR 66 TC 41 Z9 41 U1 1 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0095-2990 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PY 1992 VL 18 IS 3 BP 305 EP 329 DI 10.3109/00952999209026069 PG 25 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA JF818 UT WOS:A1992JF81800006 PM 1329493 ER PT J AU GREEN, L AF GREEN, L TI GENE-THERAPY - MEDICINE FOR THE FUTURE SO AMERICAN JOURNAL OF HOSPITAL PHARMACY LA English DT Editorial Material RP GREEN, L (reprint author), NIH,CTR CLIN,DEPT PHARM,BLDG 10,ROOM 1N 257,BETHESDA,MD 20892, USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 0002-9289 J9 AM J HOSP PHARM JI Am. J. Hosp. Pharm. PD JAN PY 1992 VL 49 IS 1 BP 172 EP 173 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GX443 UT WOS:A1992GX44300030 PM 1570861 ER PT J AU CHAPMAN, MM MINOR, JR AF CHAPMAN, MM MINOR, JR TI LYMPHOMA IN AIDS PATIENTS RECEIVING LONG-TERM ANTIRETROVIRAL THERAPY SO AMERICAN JOURNAL OF HOSPITAL PHARMACY LA English DT Letter C1 NIH,CTR CLIN,DEPT PHARM,BETHESDA,MD 20892. RP CHAPMAN, MM (reprint author), PHILADELPHIA COLL PHARM & SCI,WOODLAND AVE & 43RD ST,PHILADELPHIA,PA 19104, USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 0002-9289 J9 AM J HOSP PHARM JI Am. J. Hosp. Pharm. PD JAN PY 1992 VL 49 IS 1 BP 174 EP 175 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GX443 UT WOS:A1992GX44300031 PM 1570862 ER PT J AU CORSO, DM MINOR, JR AF CORSO, DM MINOR, JR TI ACETYLCYSTEINE IN HIV-INFECTION SO AMERICAN JOURNAL OF HOSPITAL PHARMACY LA English DT Letter ID CYSTEINE C1 NIH,CTR CLIN,DEPT PHARM,BETHESDA,MD 20892. RP CORSO, DM (reprint author), MEM SLOAN KETTERING CANC CTR,1275 YORK AVE,NEW YORK,NY 10021, USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 0002-9289 J9 AM J HOSP PHARM JI Am. J. Hosp. Pharm. PD JAN PY 1992 VL 49 IS 1 BP 175 EP 176 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GX443 UT WOS:A1992GX44300032 PM 1570863 ER PT J AU EVELETH, PB AF EVELETH, PB TI CONSIDERATIONS OF AGING RESEARCH FOR HUMAN BIOLOGISTS SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Editorial Material RP EVELETH, PB (reprint author), NIA,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1042-0533 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PY 1992 VL 4 IS 1 BP 1 EP 2 DI 10.1002/ajhb.1310040102 PG 2 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA HG760 UT WOS:A1992HG76000001 ER PT J AU KINSELLA, K SUZMAN, R AF KINSELLA, K SUZMAN, R TI DEMOGRAPHIC DIMENSIONS OF POPULATION AGING IN DEVELOPING-COUNTRIES SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Article; Proceedings Paper CT JOINT SYMP OF THE AMERICAN ASSOC OF PHYSICAL ANTHROPOLOGISTS / HUMAN BIOLOGY COUNCIL : RESEARCH ON AGING AND OLDER PERSONS CY APR 05, 1990 CL MIAMI BEACH, FL SP AMER ASSOC PHYS ANTHR, HUMAN BIOL COUNCIL AB Several demographic aspects of population aging in developing countries are considered: the older old, the median age of a population, life expectancy and mortality, functional status and disability, sex differences, urbanization, and the labor force. While the demographic impact of population aging is becoming better appreciated, the descriptive epidemiology of age-related changes in health and physical functioning in developing countries is still at an early stage. C1 NIA,BETHESDA,MD 20892. RP KINSELLA, K (reprint author), US BUR CENSUS,CTR INT RES,SUITLAND,MD 20233, USA. NR 11 TC 17 Z9 18 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1042-0533 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PY 1992 VL 4 IS 1 BP 3 EP 8 DI 10.1002/ajhb.1310040103 PG 6 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA HG760 UT WOS:A1992HG76000002 ER PT J AU PEARSON, JD BRANT, LJ MORRELL, CHH METTER, EJ FOZARD, JL AF PEARSON, JD BRANT, LJ MORRELL, CHH METTER, EJ FOZARD, JL TI LONGITUDINAL PATTERNS OF CHANGE AS A RESEARCH TOOL - PROSTATE SPECIFIC ANTIGEN, PROSTATE DISEASE, AND AGING SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Meeting Abstract C1 NIA,LONGITUDINAL STUDIES BRANCH,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,DEPT UROL,BALTIMORE,MD 21218. RI Fozard, James Leonard/B-3660-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1042-0533 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PY 1992 VL 4 IS 1 BP 147 EP 147 PG 1 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA HG760 UT WOS:A1992HG76000043 ER PT J AU SHEN, LY LIU, JZ LIN, LM MIAO, HC SONG, GY ZAN, XL CHIN, CT WEITZ, CA GARRUTO, RM AF SHEN, LY LIU, JZ LIN, LM MIAO, HC SONG, GY ZAN, XL CHIN, CT WEITZ, CA GARRUTO, RM TI DEVELOPMENTAL-CHANGES IN HEMATOLOGICAL CHARACTERISTICS AMONG HAN AND TIBETAN BOYS BORN AND RAISED AT HIGH-ALTITUDE IN WESTERN CHINA SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Meeting Abstract C1 BEIJING MED UNIV,HOSP 1,BEIJING,PEOPLES R CHINA. GUINAN CTY HOSP,GUINAN,PEOPLES R CHINA. MADO CTY HOSP,MADO,PEOPLES R CHINA. TEMPLE UNIV,PHILADELPHIA,PA 19122. NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1042-0533 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PY 1992 VL 4 IS 1 BP 149 EP 149 PG 1 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA HG760 UT WOS:A1992HG76000047 ER PT J AU WEITZ, CA GARRUTO, RM LIU, RL ZHOU, J SHEN, LY MIAO, HC YUAN, KF GANG, Q MA, TY LIU, JZ LIN, LM CHIN, CT AF WEITZ, CA GARRUTO, RM LIU, RL ZHOU, J SHEN, LY MIAO, HC YUAN, KF GANG, Q MA, TY LIU, JZ LIN, LM CHIN, CT TI GROWTH OF CHEST SIZE AND PULMONARY-FUNCTION AMONG TIBETAN AND HAN BOYS BORN AND RAISED AT 3200 M AND 4300 M IN WESTERN CHINA SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Meeting Abstract C1 TEMPLE UNIV,PHILADELPHIA,PA 19122. NIH,BETHESDA,MD 20892. QINGHAI PROV HOSP MATERNAL & CHILD HLTH,DEPT CHILD HLTH,XINING,PEOPLES R CHINA. XINING FIRST PEOPLES HOSP,XINING,PEOPLES R CHINA. BEIJING MED UNIV,HOSP 1,BEIJING,PEOPLES R CHINA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1042-0533 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PY 1992 VL 4 IS 1 BP 150 EP 150 PG 1 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA HG760 UT WOS:A1992HG76000050 ER PT J AU BLAIR, A STEWART, PA AF BLAIR, A STEWART, PA TI DO QUANTITATIVE EXPOSURE ASSESSMENTS IMPROVE RISK ESTIMATES IN OCCUPATIONAL STUDIES OF CANCER SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE RELATIVE RISKS; EXPOSURE-RESPONSE; FORMALDEHYDE; OCCUPATIONAL CANCER ID RESPIRATORY CANCER; BLADDER-CANCER; INDUSTRY-WIDE; LUNG-CANCER; WORKERS; MORTALITY; FORMALDEHYDE; EPIDEMIOLOGY; BENZENE; COHORT AB Quantitative assessment of exposure intensity is a difficult process, particularly for jobs held long ago. Despite difficulties, the use of this approach is growing in occupational epidemiology because it is hoped that the estimates will more closely approximate delivered dose than more traditional measures such as duration of exposure. If this assumption is correct, development and use of quantitative exposure estimates should reduce nondifferential exposure misclassification, sharpen exposure-response gradients, and enhance interpretation of study results. In this report, we used two methods to assess the value of quantitative exposure assessments in cancer epidemiology. In one, we surveyed the literature for investigations on occupational cancer that included assessments of both duration and intensity of exposure. The results of this survey indicated that exposure measures based on some measure of intensity of exposure yielded monotonically increasing exposure-response gradients and larger relative risks more often than those based on duration of exposure. Duration of exposure, however, occasionally provided the larger relative risks. In another approach, we found that different measures of exposure to formaldehyde classified subjects quite differently. For example, duration of exposure was unrelated to average exposure and was only weakly associated with exposure intensity or peak exposure. Because different measures of exposure may classify subjects quite differently and because quantitative estimates usually, but not always, yield larger relative risks and sharper exposure-response gradients than other measures of exposure, we believe that the prudent approach in epidemiologic investigations would be to develop quantitative estimates of exposure and to conduct analyses using several different measures of exposure, or combinations such as duration by intensity. Multiple comparisons would, however, increase chance findings. The value of such an approach is twofold. When a true association exists, use of several different measures decreases the chances of an unfortunate selection of an exposure measure that is poorly related to delivered dose, which would tend to produce negative results, and increases the chances of uncovering sharper exposure-response gradients. Use of several exposure measures in investigations that fail to exhibit an association between exposure and disease would be of value because such an approach would provide greater confidence that negative findings were not simply due to exposure misclassification. RP BLAIR, A (reprint author), NCI,OCCUPAT STUDIES SECT,EXECUTIVE PLAZA N,ROOM 418,ROCKVILLE,MD 20892, USA. NR 36 TC 41 Z9 41 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 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PY 1992 VL 21 IS 1 BP 53 EP 63 DI 10.1002/ajim.4700210108 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GY407 UT WOS:A1992GY40700007 PM 1553986 ER PT J AU ASHIZAWA, T HEJTMANCIK, JF LIU, J PERRYMAN, MB EPSTEIN, HF KOCH, DD AF ASHIZAWA, T HEJTMANCIK, JF LIU, J PERRYMAN, MB EPSTEIN, HF KOCH, DD TI DIAGNOSTIC-VALUE OF OPHTHALMOLOGIC FINDINGS IN MYOTONIC-DYSTROPHY - COMPARISON WITH RISKS CALCULATED BY HAPLOTYPE ANALYSIS OF CLOSELY LINKED RESTRICTION-FRAGMENT-LENGTH-POLYMORPHISMS SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE SPECIFICITY; LENS OPACITIES; LINKAGE ID APOLIPOPROTEIN-CII GENE; VISUAL-SYSTEM; CHROMOSOME-19; LINKAGE; LOCUS; NCOI AB To determine diagnostic value of lens opacities in myotonic dystrophy (DM), we examined 98 at-risk members of 9 DM kindreds. Haplotype analysis of restriction fragment length polymorphisms (RFLPs) using ApoC2, CKMM, and pEFD4.2 supported the diagnosis of DM in 33 and excluded the diagnosis in 51 members. The sensitivities of bilateral iridescent lens opacities, posterior cortical lens opacities, orbicularis oculi weakness, low intraocular pressure, ptosis, and ocular myotonia were 46.7, 50.0, 60.6, 59.3, 51.5, and 3.0%, while their specificities were 100.0, 100.0, 98.0, 94.1, 96.1, and 100.0%, respectively. A peripheral pigmentary degeneration and central macular lesions of retina were not found on indirect fundoscopy. In 86.2% of DM patients, bilateral iridescent lens opacities, posterior cortical lens opacities, or both were present. Unilateral iridescent lens opacities occurred in only 3 of our DM patients, and 2 of non-DM relatives showed a few unilateral iridescent particles. Posterior cortical lens opacities in DM patients always affected both eyes in this series. We conclude that 1) bilateral iridescent lens opacities and posterior cortical lens opacities are highly specific for DM and useful for establishing clinical diagnosis of DM, 2) unilateral iridescent lens opacities are infrequent in DM and are seen in some non-DM members, and 3) ocular myotonia and clinical retinopathies are rare in DM. C1 BAYLOR COLL MED,DEPT MED,INST CARDIOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT OPHTHALMOL,HOUSTON,TX 77030. VET ADM MED CTR,HOUSTON,TX 77211. NEI,BETHESDA,MD. RP ASHIZAWA, T (reprint author), BAYLOR COLL MED,DEPT NEUROL,1 BAYLOR PL,HOUSTON,TX 77030, USA. NR 28 TC 19 Z9 19 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JAN 1 PY 1992 VL 42 IS 1 BP 55 EP 60 DI 10.1002/ajmg.1320420113 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA GW607 UT WOS:A1992GW60700012 PM 1364051 ER PT J AU COLLINS, FA MURPHY, DL REISS, AL SIMS, KB LEWIS, JG FREUND, L KAROUM, F ZHU, DP MAUMENEE, IH ANTONARAKIS, SE AF COLLINS, FA MURPHY, DL REISS, AL SIMS, KB LEWIS, JG FREUND, L KAROUM, F ZHU, DP MAUMENEE, IH ANTONARAKIS, SE TI CLINICAL, BIOCHEMICAL, AND NEUROPSYCHIATRIC EVALUATION OF A PATIENT WITH A CONTIGUOUS GENE SYNDROME DUE TO A MICRODELETION XP11.3 INCLUDING THE NORRIE DISEASE LOCUS AND MONOAMINE-OXIDASE (MAOA AND MAOB) GENES SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE NORRIE DISEASE; MONOAMINE-OXIDASE; X-CHROMOSOME; CONTIGUOUS GENE SYNDROME ID CLONED DNA-SEQUENCE; PROXIMAL SHORT ARM; X-CHROMOSOME; DIAGNOSTIC-INTERVIEW; PRESSOR SENSITIVITY; PRENATAL-DIAGNOSIS; CLOSE LINKAGE; DELETION; PLASMA; INACTIVATION AB Norrie disease is a rare X-linked recessive disorder characterized by blindness from infancy. The gene for Norrie disease has been localized to Xp11.3. More recently, the genes for monoamine oxidase (MAOA, MAOB) have been mapped to the same region. This study evaluates the clinical, biochemical, and neuropsychiatric data in an affected male and 2 obligate heterozygote females from a single family with a submicroscopic deletion involving Norrie disease and MAO genes. The propositus was a profoundly retarded, blind male; he also had neurologic abnormalities including myoclonus and stereotopy-habit disorder. Both obligate carrier females had a normal IQ. The propositus' mother met diagnostic criteria for "chronic hypomania and schizotypal features." The propositus' MAO activity was undetectable and the female heterozygotes had reduced levels comparable to patients receiving MAO inhibiting antidepressants. MAO substrate and metabolite abnormalities were found in the propositus' plasma and CSF. This study indicates that subtle biochemical and possibly neuropsychiatric abnormalities may be detected in some heterozygotes with the microdeletion in Xp11.3 due to loss of the gene product for the MAO genes; this deletion can also explain some of the complex phenotype of this contiguous gene syndrome in the propositus. C1 JOHNS HOPKINS UNIV HOSP,SCH MED,CTR MED GENET,CMSC 1003,600 N WOLFE ST,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV HOSP,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. NIMH,CLIN SCI LAB,CLIN CTR 10-3D41,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT,DIV CHILD PSYCHIAT,BEHAV GENET RES CTR,BALTIMORE,MD 21205. KENNEDY INST,BALTIMORE,MD. MASSACHUSETTS GEN HOSP,CTR NEUROSCI,MOLEC NEUROGENET LAB,BOSTON,MA 02114. JOHNS HOPKINS UNIV,SCH MED,WILMER EYE INST,JOHNS HOPKINS CTR HEREDITARY EYE DIS,BALTIMORE,MD 21205. RI Antonarakis, Stylianos/N-8866-2014 OI Antonarakis, Stylianos/0000-0001-8907-5823 FU NHGRI NIH HHS [HG00373] NR 50 TC 61 Z9 61 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JAN 1 PY 1992 VL 42 IS 1 BP 127 EP 134 DI 10.1002/ajmg.1320420126 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA GW607 UT WOS:A1992GW60700025 PM 1308352 ER PT J AU MANOLIO, TA FURBERG, CD AF MANOLIO, TA FURBERG, CD TI AGE AS A PREDICTOR OF OUTCOME - WHAT ROLE DOES IT PLAY SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID CORONARY-ARTERY DISEASE; ACUTE MYOCARDIAL-INFARCTION; HEART-DISEASE; CARDIOVASCULAR-DISEASE; BYPASS-SURGERY; RISK-FACTORS; MORTALITY; SMOKING; OLDER; TRIAL C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. NR 43 TC 14 Z9 14 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JAN PY 1992 VL 92 IS 1 BP 1 EP 6 DI 10.1016/0002-9343(92)90007-X PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA HA866 UT WOS:A1992HA86600001 PM 1731496 ER PT J AU HANSEN, KA OPSAHL, MS NIEMAN, LK BAKER, JR KLEIN, TA AF HANSEN, KA OPSAHL, MS NIEMAN, LK BAKER, JR KLEIN, TA TI NATURAL-KILLER-CELL ACTIVITY FROM PREGNANT SUBJECTS IS MODULATED BY RU-486 SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE NATURAL KILLER CELLS; PREGNANCY; RU-486 ID MURINE TROPHOBLAST; MEDIATED-IMMUNITY; CYTO-TOXICITY; SERUM FACTORS; NK CELLS; PROGESTERONE; INDUCTION; SENSITIVITY; LYMPHOCYTES; INTERFERON AB Natural killer cells form an integral component of the body's innate immune system. Natural killer cell activity is reduced during pregnancy, especially in the latter half. To investigate the role progesterone may play in immunomodulating natural killer cell activity during pregnancy, we evaluated the effect of RU 486 on natural killer cells isolated from pregnant subjects. Natural killer cell activity was measured with an 18-hour, Chromium 51 release, microcytotoxicity assay with K-562 cells as target cells. We demonstrated that RU 486, in a concentration range from 5 to 40-mu-mol/L, augmented natural killer activity threefold to fivefold over baseline. This augmentation of activity was suppressed to baseline by the addition of excess progesterone. The addition of hydrocortisone resulted in an insignificant reduction in this augmented activity. This study suggests that progesterone may play a role as an immunomodulating factor in maternal acceptance of the fetal allograft. C1 WALTER REED ARMY MED CTR, DEPT OBSTET & GYNECOL, WASHINGTON, DC 20307 USA. NATL NAVAL MED CTR, BETHESDA, MD 20814 USA. NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. OI Opsahl, Michael/0000-0002-8754-7943 NR 28 TC 31 Z9 31 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 1992 VL 166 IS 1 BP 87 EP 90 PN 1 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA HA451 UT WOS:A1992HA45100021 PM 1733224 ER PT J AU MERLO, GR VENESIO, T BERNARDI, A CANALE, L GAGLIA, P LAURO, D CAPPA, APM CALLAHAN, R LISCIA, DS AF MERLO, GR VENESIO, T BERNARDI, A CANALE, L GAGLIA, P LAURO, D CAPPA, APM CALLAHAN, R LISCIA, DS TI LOSS OF HETEROZYGOSITY ON CHROMOSOME-17P13 IN BREAST CARCINOMAS IDENTIFIES TUMORS WITH HIGH PROLIFERATION INDEX SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID RETINOBLASTOMA GENE; CELL-PROLIFERATION; CANCER PATIENTS; P53; MUTATIONS; IMMORTALIZATION; TRANSFORMATION; HOMOZYGOSITY; PROGRESSION; PREDICTION AB The capacity of breast tumor cells to proliferate is considered a potential prognostic factor together with other histopathologic parameters. The authors determined the proliferation index on a large panel of human primary breast tumors by measuring the levels of incorporation of bromodeoxyuridine (BrdU) by fresh tumor specimens in culture. Previous analysis showed that the percentage of cells entering the S-phase of the cell cycle strongly correlates with tumor grade, tumor size, and estrogen and progesterone receptor status. The capacity of tumor cells to proliferate might be associated with specific genetic mutations in primary tumors. To test this hypothesis, a panel of 96 human breast carcinomas, for which the BrdU labeling index (LI) was known, were tested for loss of heterozygosity (LOH) or increased copy number (ICN) at chromosomes 1q, 3p, 13q, 17p, and 18q. On chromosome 17p, LOH and ICN were observed in 27% and 12%, respectively, of the informative breast tumors. The LOH on chromosome 17p was significantly associated with tumors having an elevated BrdU proliferation index (P = 0.022). No association (P = 0.45) was observed between BrdU LI and tumor size (T2 + T3 compared with T1), tumor grade, and lymph node status. Increased copy number on chromosome 17p, LOH or ICN on 1q, and LOH on 13q14, 18q, and 3p also showed no significant correlation with cell kinetic parameters. These data are consistent with the presence of a gene or genes on chromosome 17p13 near the YNZ22.1 locus whose normal functioning is necessary for controlling breast tumor cells proliferation in vivo. C1 S GIOVANNI VECCHIO HOSP,PATHOL SECT,USL-1,VIA CAVOUR 31,I-10123 TURIN,ITALY. NIH,TUMOR IMMUNOL & BIOL LAB,ONCOGENET SECT,BETHESDA,MD 20892. NR 51 TC 43 Z9 43 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 1992 VL 140 IS 1 BP 215 EP 223 PG 9 WC Pathology SC Pathology GA GZ636 UT WOS:A1992GZ63600022 PM 1731526 ER PT J AU LU, DJ TAKAI, A LETO, TL GRINSTEIN, S AF LU, DJ TAKAI, A LETO, TL GRINSTEIN, S TI MODULATION OF NEUTROPHIL ACTIVATION BY OKADAIC ACID, A PROTEIN PHOSPHATASE INHIBITOR SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE SUPEROXIDE; RESPIRATORY BURST; PHOSPHORYLATION; PROTEIN KINASE; LEUKOCYTE (HUMAN) ID CHRONIC GRANULOMATOUS-DISEASE; SUPEROXIDE PRODUCTION; KINASE-C; ELECTROPERMEABILIZED NEUTROPHILS; RESPIRATORY BURST; NADPH-OXIDASE; PHOSPHORYLATION; STAUROSPORINE; STIMULATION; SIGNAL AB We determined the effects of okadaic acid (OA), a specific inhibitor of protein phosphatases 1 (PP1) and 2A (PP2A), on protein phosphorylation and on the activation of the NADPH oxidase in human neutrophils. In otherwise unstimulated cells, OA induced phosphoprotein accumulation, revealing the presence of constitutively active protein kinases. Pulse-chase experiments in electropermeabilized cells confirmed that this effect was due, at least in part, to inhibition of dephosphorylation. OA potentiated phosphoprotein accumulation induced by phorbol esters and by the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP). In phorbol ester-stimulated cells, OA prolonged the respiratory response after inhibition of protein kinase C (PKC) with staurosporine, consistent with a reduced rate of dephosphorylation of active phosphorylated components. Similarly, OA delayed the inactivation of the burst after displacement of FMLP from its receptor by a competitive antagonist. This suggests that the substrates of the protein kinases activated by FMLP are dephosphorylated by PP1 and/or PP2A. That phosphatases control the intensity and duration of the respiratory response is suggested by the finding that OA magnified and prolonged the oxidative burst elicited by FMLP. In contrast, pretreatment with OA produced a time-dependent inhibition of the phorbol ester-induced respiratory burst. Under conditions where inhibition of the phorbol ester response was nearly complete, activation by the chemoattractant peptide not only persisted but was in fact accentuated. These findings provide strong evidence that receptor-mediated stimulation of the NADPH oxidase can occur by pathways not involving PKC. C1 HOSP SICK CHILDREN,DIV CELL BIOL,555 UNIV AVE,TORONTO M5G 1X8,ONTARIO,CANADA. NAGOYA UNIV,DEPT PHYSIOL,NAGOYA,AICHI 466,JAPAN. NIAID,HOST DEF LAB,BETHESDA,MD 20814. NR 30 TC 58 Z9 58 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JAN PY 1992 VL 262 IS 1 BP C39 EP C49 PN 1 PG 11 WC Physiology SC Physiology GA HA742 UT WOS:A1992HA74200007 PM 1310215 ER PT J AU FLESSNER, MF WALL, SM KNEPPER, MA AF FLESSNER, MF WALL, SM KNEPPER, MA TI AMMONIUM AND BICARBONATE TRANSPORT IN RAT OUTER MEDULLARY COLLECTING DUCTS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE AMMONIA; ACID-BASE; PERMEABILITY; RENAL EPITHELIA; KIDNEY ID THICK ASCENDING LIMB; KIDNEY; PH AB Previous in vitro studies have demonstrated spontaneous bicarbonate absorption in the outer stripe portion of the rat outer medullary collecting duct (OMCD) and inner medullary collecting duct, but net acid transport has not been studied in the inner stripe of the rat OMCD (OMCD(IS)). When we perfused isolated OMCD(IS) segments with identical bath and perfusate solutions containing HCO3- and NH4Cl, HCO3- was spontaneously absorbed, and total ammonia was spontaneously secreted at rapid rates in tubules from both deoxycorticosterone (DOC)-treated and untreated rats. We next measured the NH3 flux due to imposed NH3 concentration gradients. Carbonic anhydrase (CA), when added to the lumen, enhanced the NH3 flux, implying an absence of endogenous CA. The NH3 permeability was 0.0042 +/- 0.0007 cm/s. By measuring the luminal pH in perfused OMCD(IS) segments with an imposed lumen-to-bath NH3 gradient, we determined the pH at the end of the lumen to be 0.23 units below the equilibrium pH calculated from the simultaneously measured total CO2 concentration in collected fluid, confirming the lack of luminal CA. These results are consistent with the view that ammonium secretion in the OMCD(IS) occurs predominantly by H+ secretion and parallel NH3 diffusion. A luminal disequilibrium pH due to H+ secretion in the absence of endogenous luminal CA enhances the NH3 entry rate. Spontaneous net acid secretion appears to occur more rapidly in the OMCD than in other parts of the rat collecting duct system. RP FLESSNER, MF (reprint author), NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892, USA. NR 22 TC 38 Z9 38 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JAN PY 1992 VL 262 IS 1 BP F1 EP F7 PN 2 PG 7 WC Physiology SC Physiology GA HA743 UT WOS:A1992HA74300066 PM 1733285 ER PT J AU HEINEMAN, FW KUPRIYANOV, VV MARSHALL, R FRALIX, TA BALABAN, RS AF HEINEMAN, FW KUPRIYANOV, VV MARSHALL, R FRALIX, TA BALABAN, RS TI MYOCARDIAL OXYGENATION IN THE ISOLATED WORKING RABBIT HEART AS A FUNCTION OF WORK SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE OXIDATIVE PHOSPHORYLATION; CYTOCHROME AA3; CYTOCHROME-C OXIDASE; MYOGLOBIN; CORONARY FLOW; AFTERLOAD; ISOPROTERENOL; BETA-STIMULATION ID MAGNETIC-RESONANCE ANALYSIS; CREATINE-KINASE REACTION; PERFUSED RAT-HEART; RESPIRATORY CONTROL; P-31 NMR; INVIVO; FLUORESCENCE; CONSUMPTION; METABOLITE; DEPENDENCE AB Myocardial O2 consumption (MVO2) was stimulated up to two-fold by either increasing afterload or beta-receptor stimulation in working normothermic isolated rabbit hearts while noninvasively monitoring the O2 delivery or phosphate compounds (total n = 48). Intracellular O2 delivery was estimated with the use of myocardial optical absorbance changes centered at 603.5 and 582 nm that correlate with cytochrome aa3 redox and myoglobin oxygenation states. Phosphate-containing metabolites (ATP, phosphocreatine, free ADP) were assessed using NP nuclear magnetic resonance spectroscopy. Measurements were made both with intact autoregulation and after maximal vasodilation by 1-mu-M nitroprusside (NP). When afterload was used to increase MVO2, absorbance decreased at 603.5 nm and increased at 582 nm, consistent with a 10-15% increase in myocardial oxygenation, without an associated change in cardiac phosphate compounds. NP caused a further increase in myocardial oxygenation and venous PO2 consistent with an increase in the O2 supply-to-demand ratio. Increases in MVO2 due to beta-stimulation alone were not associated with changes in 603.5-nm absorbance or phosphate compounds, but in combination with NP were accompanied by increased oxygenation, venous PO2, and cardiac phosphocreatine. KCl arrest caused maximal increases in oxygenation and phosphocreatine. These findings suggest that neither cytochrome aa3 nor myoglobin in the isolated working rabbit heart is fully oxidized or oxygenated, respectively. Furthermore, the oxygenation state of the tissue varied both with afterload-induced changes in cardiac work and with changes in O2 supply/demand. C1 NATL CARDIOL RES CTR,INST EXPTL CARDIOL,BIOENERGET LAB,MOSCOW 121552,USSR. MICHIGAN STATE UNIV,COLL HUMAN MED,E LANSING,MI 48824. RP HEINEMAN, FW (reprint author), NHLBI,CARDIAC ENERGET LAB,BETHESDA,MD 20892, USA. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 38 TC 43 Z9 43 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JAN PY 1992 VL 262 IS 1 BP H255 EP H267 PN 2 PG 13 WC Physiology SC Physiology GA HA743 UT WOS:A1992HA74300036 PM 1346358 ER PT J AU SAKAI, M DANZIGER, RS XIAO, RP SPURGEON, HA LAKATTA, EG AF SAKAI, M DANZIGER, RS XIAO, RP SPURGEON, HA LAKATTA, EG TI CONTRACTILE RESPONSE OF INDIVIDUAL CARDIAC MYOCYTES TO NOREPINEPHRINE DECLINES WITH SENESCENCE SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE SENESCENT HEART; BETA-ADRENERGIC STIMULATION; CALCIUM ID BETA-ADRENERGIC RECEPTORS; ADULT-RAT CARDIOMYOCYTES; VENTRICULAR MYOCYTES; ADENYLATE-CYCLASE; INTACT MUSCLE; MYOCARDIUM; HEART; RESPONSIVENESS; HYPERTROPHY; DECREASE AB The present study utilized individual isolated left ventricular cardiac myocytes from hearts of animals of a broad age range to evaluate the response to norepinephrine and to other stimuli that augment myocardial cell contractile performance. During electrical stimulation before drugs neither the amplitude nor the velocity of shortening normalized for resting cell length differed among cells isolated from 2-, 6- to 8-, or 24-mo-old animals. Norepinephrine augmented twitch amplitude and velocity about fourfold in cells from 2-mo-old hearts but only by 2.5-fold in cells from 24-mo-old hearts (age effect, P < 0.001). In contrast, the contractile response to increases in bathing [Ca2+] or to the addition of the calcium channel agonist BAY K 8644 or of 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (CPT cAMP) did not vary with age. These results indicate that the age-associated contractile deficit during beta-adrenergic stimulation is specific to the beta-adrenergic pathway and an age-associated deficit in the net production of cAMP. This can be attributed to a diminished cardiac myocyte response to beta-adrenergic agonists, in contrast to modulation of the beta-adrenergic response by other receptor agonists, which are present in intact tissue but absent under the conditions of the present study. RP SAKAI, M (reprint author), NIA,CARDIOVASC SCI LAB,GERONTOL RES CTR,BALTIMORE,MD 21224, USA. NR 32 TC 46 Z9 47 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JAN PY 1992 VL 262 IS 1 BP H184 EP H189 PN 2 PG 6 WC Physiology SC Physiology GA HA743 UT WOS:A1992HA74300027 PM 1370751 ER PT J AU BARANIUK, JN SILVER, PB LUNDGREN, JD COLE, P KALINER, MA BARNES, PJ AF BARANIUK, JN SILVER, PB LUNDGREN, JD COLE, P KALINER, MA BARNES, PJ TI BOMBESIN STIMULATES HUMAN NASAL MUCOUS AND SEROUS CELL SECRETION INVIVO SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE GASTRIN-RELEASING PEPTIDE; GLYCOCONJUGATES; MUCUS; LYSOZYME; ALBUMIN; NASAL SECRETION; SUBMUCOSAL GLANDS; VASCULAR PERMEABILITY; HUMAN NASAL PROVOCATION AB Bombesin, gastrin-related peptide (GRP), and related peptides sharing the common carboxy-terminal sequence stimulate lactoferrin (serous cell marker) and glycoconjugate (mucous cell and goblet cell marker) release from human nasal mucosal explants in vitro. In vivo, GRP released from trigeminal sensory nerves may act upon GRP-bombesin binding sites on respiratory epithelial cells and submucosal glands. To determine whether GRP-bombesin can stimulate nasal secretion in vivo, bombesin was administered to eight normal subjects by unilateral, topical administration. Secretions from both nostrils were collected for measurement of total protein, lysozyme, hexose-containing glycoconjugates, and albumin (marker of vascular permeability). Baseline secretions contained 72.0 +/- 17.3-mu-g/ml of total protein, 14 +/- 2-mu-g/ml of lysozyme, 113 +/- 44-mu-g/ml of hexose-containing glycoconjugates, and 7.8 +/- 3.4-mu-g/ml of albumin. Hexose-containing glycoconjugate secretion was significantly increased after 1 nmol (385 +/- 63-mu-g/ml, P < 0.001 by analysis of variance), 10, 100, and 1,000 nmol of bombesin, but the secretion was not dose dependent. Significant lysozyme (24 +/- 3-mu-g/ml, P < 0.05) and total protein (155 +/- 23-mu-g/ml, P < 0.01) secretion occurred after 1,000 nmol. No statistically significant changes in albumin secretion occurred at any dose. Saline had no significant effects on secretion. Therefore, bombesin stimulated secretion from submucosal glands and possibly epithelial cells in the human nose without affecting vascular permeability. C1 NATL HEART & LUNG INST, DEPT THORAC MED, LONDON SW3 6LY, ENGLAND. HVIDOVRE UNIV HOSP, DEPT INFECT DIS, DK-2650 HVIDOVRE, DENMARK. RP NIAID, ALLERG DIS SECT, CLIN INVEST LAB, BLDG 10, ROOM 11C205, BETHESDA, MD 20892 USA. NR 25 TC 16 Z9 16 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JAN PY 1992 VL 262 IS 1 BP L48 EP L52 PN 1 PG 5 WC Physiology SC Physiology GA HA742 UT WOS:A1992HA74200088 PM 1733281 ER PT J AU NOVAK, MA ONEILL, P SUOMI, SJ AF NOVAK, MA ONEILL, P SUOMI, SJ TI ADJUSTMENTS AND ADAPTATIONS TO INDOOR AND OUTDOOR ENVIRONMENTS - CONTINUITY AND CHANGE IN YOUNG-ADULT RHESUS-MONKEYS SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Article DE BEHAVIOR; CAPTIVE ENVIRONMENTS; INDIVIDUAL DIFFERENCES ID CAGE DESIGN; BEHAVIOR; PRIMATES AB Optimal environments for captive primates are assumed to be those which simulate certain ecological features and elicit a wide range of species-typical behavior patterns. Outdoor environments are often thought to be more suitable than indoor environments in that they provide more space and potentially higher levels of stimulation. The purpose of this study was to compare the long-term behavioral responses of several groups of animals that had been reared identically during the first two years of life and then exposed to different environments. Two groups were moved into separate" enriched" indoor pens while one group was moved to an outdoor area covering approximately 5 acres. The monkeys were observed during the first year of life and again in these different environments between the ages of 6 and 10. Although behaviorally similar during the first year of life, monkeys developed different response patterns to indoor and outdoor environments. Contrary to commonly held views, indoor monkeys were not more aggressive, nor did they show higher levels of stereotypical behavior. Instead, indoor monkeys exhibited higher levels of grooming, sexual posturing, tactile/oral exploration, and passive visual behavior than their outdoor counterparts. These differences are consistent with the reconciliation model of de Waal. Individual monkeys also showed remarkable stability in certain traits over the 5-year period. C1 NICHHD,COMPARAT ETHOL LAB,BETHESDA,MD 20892. RP NOVAK, MA (reprint author), UNIV MASSACHUSETTS,DEPT PSYCHOL,TOBIN HALL,AMHERST,MA 01003, USA. NR 43 TC 39 Z9 40 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PY 1992 VL 28 IS 2 BP 125 EP 138 DI 10.1002/ajp.1350280205 PG 14 WC Zoology SC Zoology GA JN786 UT WOS:A1992JN78600004 ER PT J AU SEUANEZ, HN ALVES, G LIMA, MMC BARROS, RD BARROSO, CML MUNIZ, JAPC AF SEUANEZ, HN ALVES, G LIMA, MMC BARROS, RD BARROSO, CML MUNIZ, JAPC TI CHROMOSOME-STUDIES IN CHIROPOTES-SATANAS-UTAHICKI HERSHKOVITZ, 1985 (CEBIDAE, PLATYRRHINI) - A COMPARISON WITH CHIROPOTES-SATANAS-CHIROPOTES SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Note DE CHIROPOTES; SATANAS; SUBSPECIES; KARYOLOGY ID CALLIMICO-GOELDII PRIMATES; DNA-SEQUENCES; CEBUS-APELLA; MONKEY AB Karyological characterizations of C. s. utahicki (2n = 54) and C. s. chiropotes (2n = 54) showed that these two subspecies are chromosomally very similar. In a single, isolated specimen of C. s. utahicki, however, a derived, biarmed, chromosome 14 was found in the heterozygous condition. This variant chromosome was identical with pair 10 in C. s. chiropotes in which this chromosome type was apparently fixed. Chromosome differences between these subspecies might be transitional, leading to the establishment of two different karyomorphic populations derived from a once uniform karyotypic group that split into separate allopatric subspecies. C1 CTR NACL PRIMATAS,BELEM,PARA,BRAZIL. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. UNIV FED PARA,DEPT GENET,BELEM,PARA,BRAZIL. RP SEUANEZ, HN (reprint author), INST NACL CANC,SERV GENET,PRACA CRUZ VERMELHA 23,RIO JANEIRO,BRAZIL. NR 20 TC 6 Z9 6 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 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PY 1992 VL 28 IS 3 BP 213 EP 222 DI 10.1002/ajp.1350280306 PG 10 WC Zoology SC Zoology GA JT897 UT WOS:A1992JT89700005 ER PT J AU FRAGASZY, DM BOINSKI, S WHIPPLE, J AF FRAGASZY, DM BOINSKI, S WHIPPLE, J TI BEHAVIORAL SAMPLING IN THE FIELD - COMPARISON OF INDIVIDUAL AND GROUP SAMPLING METHODS SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Article DE BEHAVIORAL OBSERVATION; FOCAL SAMPLING; SCAN SAMPLING ID MONKEYS SAIMIRI-OERSTEDI; COSTA-RICA AB Sampling decisions affect the efficiency and reliability of data collection, and the appropriateness of the data for analyses of group and individual behavior. We evaluate the correspondence between interval sampling of individual behavior at high temporal density (focal interval sampling) with interval sampling of group behavior at lower density (group scan sampling) in two field studies with neotropical primates, capuchins and squirrel monkeys. The two methods provided consistent estimates of population means and variance for activity profiles, foraging activities, and height above ground. The correspondence between mean values with the two methods was greater when group sampling included individual identities than when a nominal scoring scheme was used. A group scan method (without identification of individuals) can be used alone when information is needed within a brief time, such as initial description of activity budgets of a population. Although individual identities take time to learn, data sets in which the individual is the unit of analysis provide several other kinds of analytical possibilities. We recommend use of a mixed sampling regime containing both of these elements (focal and group sampling) as a good way to minimize the time costs of data collection and as a means to evaluate reliability of data collection by a solo observer. C1 NICHHD,NIH ANIM CTR,COMPARAT ETHOL LAB,POOLESVILLE,MD. WASHINGTON STATE UNIV,DEPT PSYCHOL,PULLMAN,WA 99164. RP FRAGASZY, DM (reprint author), UNIV GEORGIA,DEPT PSYCHOL,ATHENS,GA 30602, USA. NR 24 TC 42 Z9 43 U1 0 U2 31 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PY 1992 VL 26 IS 4 BP 259 EP 275 DI 10.1002/ajp.1350260404 PG 17 WC Zoology SC Zoology GA HW873 UT WOS:A1992HW87300003 ER PT J AU CORYELL, W ENDICOTT, J WINOKUR, G AF CORYELL, W ENDICOTT, J WINOKUR, G TI ANXIETY SYNDROMES AS EPIPHENOMENA OF PRIMARY MAJOR DEPRESSION - OUTCOME AND FAMILIAL PSYCHOPATHOLOGY SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PRIMARY AFFECTIVE-DISORDER; FOLLOW-UP; PANIC DISORDER; ENDOGENOUS-DEPRESSION; GENETIC-FACTORS; BIPOLAR-II; DSM-III; DIAGNOSIS; NEUROSIS; PROBANDS AB Objective: Anxiety symptoms often appear within depressive episodes, but their significance is uncertain. This study sought to determine whether they indicate the coexistence of a separate disease process and whether they have prognostic significance. Method: A series of patients with primary depression who entered a follow-up and family study included 37 who also had obsessions or compulsions, 93 who had panic attacks, 101 who had phobias, and 196 who had none of these anxiety syndromes. Each of the overlapping groups defined by the presence of a specific anxiety syndrome was compared to the group that had none of these syndromes with respect to baseline demographic, phenomenological, and historical features, illness rates among directly interviewed relatives, and diagnostic stability and clinical outcome at semiannual follow-ups over a period of 5 years. Results: Depressive symptoms at intake were more longstanding and severe among patients with specific anxiety symptoms, and these patients went on to experience more depressive morbidity during the ensuing 5 years. The development of autonomous anxiety disorders was rare, however, and specific anxiety syndromes in the probands did not increase risks for the corresponding disorders among relatives. Conclusions: When restricted to episodes of major depression, anxiety syndromes appear to be prognostically significant epiphenomena rather than indicators of an additional disorder. C1 NIMH,COLLABORAT PROGRAM PSYCHOBIOL DEPRESS CLIN STUDIES,BETHESDA,MD 20892. NR 29 TC 125 Z9 126 U1 2 U2 3 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 1992 VL 149 IS 1 BP 100 EP 107 PG 8 WC Psychiatry SC Psychiatry GA GX040 UT WOS:A1992GX04000015 PM 1728156 ER PT J AU AKISKAL, HS WEISE, RE AF AKISKAL, HS WEISE, RE TI THE CLINICAL SPECTRUM OF SO-CALLED MINOR DEPRESSIONS SO AMERICAN JOURNAL OF PSYCHOTHERAPY LA English DT Article ID EPISODIC MAJOR DEPRESSION; SUB-AFFECTIVE DISORDERS; BIPOLAR-II DISORDERS; FOLLOW-UP; NEUROTIC DEPRESSION; SOCIOENVIRONMENTAL CHARACTERISTICS; CHARACTEROLOGICAL DEPRESSIONS; SEMISTRUCTURED INTERVIEW; FAMILIAL CHARACTERISTICS; DYSTHYMIC DISORDER AB This selective review of recent clinical research on neurotic depressive and dysthymic disorders observed in psychiatric settings reveals that, far being "minor," they typically begin early in life against a familial background loaded with mood disorders, and are often complicated by superimposed major depressive-and even hypomanic-episodes, fluctuating or continued symptomatic chronicity, impaired leisure functions, conjugal conflicts, and even suicide. C1 NIMH,MOOD ANXIETY & PERSONAL DISORDERS RES BRANCH,ROCKVILLE,MD 20857. RP AKISKAL, HS (reprint author), NIMH,AFFECT & RELATED DISORDERS,5600 FISHERS LANE,ROOM 10C-24,ROCKVILLE,MD 20857, USA. NR 69 TC 41 Z9 43 U1 4 U2 4 PU ASSN ADVAN PSYCHOTHERAPY PI BRONX PA BELFER EDUC CENTER, ROOM 402 ALBERT EINSTEIN COLL MED 1300 MORRIS PARK AVE, BRONX, NY 10461-1602 SN 0002-9564 J9 AM J PSYCHOTHER JI Am. J. Psychother. PD JAN PY 1992 VL 46 IS 1 BP 9 EP 22 PG 14 WC Psychology, Clinical; Psychiatry; Psychology; Psychology, Psychoanalysis SC Psychology; Psychiatry GA HE954 UT WOS:A1992HE95400003 PM 1543256 ER PT J AU SHOPLAND, DR NIEMCRYK, SJ MARCONI, KM AF SHOPLAND, DR NIEMCRYK, SJ MARCONI, KM TI GEOGRAPHIC AND GENDER VARIATIONS IN TOTAL TOBACCO USE SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Note ID CIGARETTE-SMOKING; UNITED-STATES AB This study is the first to provide complete information on prevalence rates by gender and geographic variation for each type of tobacco product used in the United States. Results indicate that, in nearly half of all states, total tobacco use in men exceeded 40% and, in four states, exceeded 50%. In women, only Nevada, Kentucky, and Michigan reported prevalence exceeding 33%. Results also indicate, however, that concurrent use of multiple tobacco forms is relatively rare. Substantial regional variation in male total tobacco use was evident, with southern males exhibiting the highest prevalence rate (44.6%). As a result, this region represents a target group in special need of comprehensive and effective tobacco use interventions. C1 NCI,CANC CONTROL SCI PROGRAM,BETHESDA,MD 20892. ROW SCI INC,ROCKVILLE,MD. NR 12 TC 25 Z9 25 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JAN PY 1992 VL 82 IS 1 BP 103 EP 106 DI 10.2105/AJPH.82.1.103 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA HL399 UT WOS:A1992HL39900023 PM 1536310 ER PT J AU ROM, WN TRAVIS, WD BRODY, AR AF ROM, WN TRAVIS, WD BRODY, AR TI CELLULAR AND MOLECULAR-BASIS OF THE ASBESTOS-RELATED DISEASES - REPLY SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Letter ID LUNG-CANCER; FIBROSIS C1 NCI,BETHESDA,MD 20892. NIEHS,RES TRIANGLE PK,NC 27709. RP ROM, WN (reprint author), NYU MED CTR,NEW YORK,NY 10016, USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD JAN PY 1992 VL 145 IS 1 BP 238 EP 239 PG 2 WC Respiratory System SC Respiratory System GA GZ104 UT WOS:A1992GZ10400048 ER PT J AU SANKARAN, L AF SANKARAN, L TI A SIMPLE QUANTITATIVE ASSAY FOR CHLORAMPHENICOL ACETYLTRANSFERASE BY DIRECT EXTRACTION OF THE LABELED PRODUCT INTO SCINTILLATION COCKTAIL SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID CELLS; EXPRESSION; GENE RP SANKARAN, L (reprint author), NIDDK,DIABET BRANCH,BLDG 10,ROOM 8S243,BETHESDA,MD 20892, USA. NR 12 TC 21 Z9 21 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JAN PY 1992 VL 200 IS 1 BP 180 EP 186 DI 10.1016/0003-2697(92)90296-J PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA GY792 UT WOS:A1992GY79200028 PM 1595893 ER PT J AU MARKOWITZ, A ROBINSON, RC OMATA, Y FRIEDMAN, FK AF MARKOWITZ, A ROBINSON, RC OMATA, Y FRIEDMAN, FK TI A FLASH-PHOTOLYSIS INSTRUMENT WITH DIGITAL SMOOTHING OF DATA USING A FAST FOURIER-TRANSFORM SO ANALYTICAL INSTRUMENTATION LA English DT Article AB Laser flash photolysis is a useful technique for disruption of photolabile chemical bonds. The kinetics of the subsequent reformation of such bonds can then be monitored with a suitable detection system. This technique has proven useful for following the reassociaton kinetics of hemeproteins with carbon monoxide. We describe the construction of this apparatus using readily available components, along with microcomputer based signal acquisition and digital filtering of data using a fast Fourier transform. The application of this apparatus to measurement of the association of cytochrome P450 with carbon monoxide is described. C1 NCI,BETHESDA,MD 20892. RP MARKOWITZ, A (reprint author), NIH,BIOMED INSTRUMENTAT & ENGN BRANCH,BETHESDA,MD 20892, USA. RI Friedman, Fred/D-4208-2016 NR 7 TC 12 Z9 12 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0743-5797 J9 ANAL INSTRUM PY 1992 VL 20 IS 4 BP 213 EP 221 PG 9 WC Chemistry, Analytical; Instruments & Instrumentation SC Chemistry; Instruments & Instrumentation GA JX507 UT WOS:A1992JX50700001 ER PT J AU ALEXANDER, LJ LEVINE, WB TENG, CT BEATTIE, CW AF ALEXANDER, LJ LEVINE, WB TENG, CT BEATTIE, CW TI CLONING AND SEQUENCING OF THE PORCINE LACTOFERRIN CDNA SO ANIMAL GENETICS LA English DT Note DE ARTIODACTYL; LACTATION; LACTOFERRIN; SUS-SCROFA; SWINE ID HUMAN LACTOTRANSFERRIN; NUCLEOTIDE-SEQUENCE; MESSENGER-RNA; TRANSFERRIN; ESTROGEN; ACID AB cDNA clones encoding the entire porcine lactoferrin protein were isolated and sequenced. The porcine lactoferrin cDNA sequence presented here is 2259 bp in length and encodes a leader peptide of 19 amino acids and a mature protein of 684 amino acids. Comparisons with other lactoferrins indicate a single glycosylation site. The iron- and anion-binding sites, and the cysteine residues involved in disulphide bonds,are conserved between the lactoferrin proteins. C1 NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. RP ALEXANDER, LJ (reprint author), UNIV ILLINOIS,DIV SURG ONCOL,840 S WOOD ST M-C 820,CHICAGO,IL 60612, USA. NR 17 TC 16 Z9 17 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0268-9146 J9 ANIM GENET JI Anim. Genet. PY 1992 VL 23 IS 3 BP 251 EP 256 PG 6 WC Agriculture, Dairy & Animal Science; Genetics & Heredity SC Agriculture; Genetics & Heredity GA HY528 UT WOS:A1992HY52800007 PM 1503259 ER PT J AU SMITH, PD QUINN, TC STROBER, W JANOFF, EN MASUR, H AF SMITH, PD QUINN, TC STROBER, W JANOFF, EN MASUR, H TI GASTROINTESTINAL INFECTIONS IN AIDS SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IMMUNE-DEFICIENCY SYNDROME; MYCOBACTERIUM-AVIUM COMPLEX; CYTOMEGALO-VIRUS INFECTION; ANTI-BACTERIAL ACTIVITY; HOMOSEXUAL MEN; HERPES-SIMPLEX; IMMUNOCOMPROMISED PATIENTS; HUMAN CRYPTOSPORIDIOSIS; SALMONELLA-TYPHIMURIUM AB As the largest lymphoid organ in the body, the gastrointestinal tract is a potential reservoir for human immunodeficiency virus (HIV), the causative agent of the acquired immunodeficiency syndrome (AIDS), and it is an important site for HIV-induced immunodeficiency. The resulting defects in cellular and humoral defense mechanisms predispose the gastrointestinal tract to a spectrum of viral, fungal, bacterial, and protozoan pathogens that cause relentless morbidity and, in some cases, death. With a thorough diagnostic evaluation, physicians can identify one or more of these pathogens in a majority of patients with AIDS who have gastrointestinal symptoms. The identification of enteric pathogens in patients with AIDS is important because an increasing array of therapeutic regimens is becoming available to treat many of these infections. RP SMITH, PD (reprint author), NIH,BLDG 30,ROOM 322,BETHESDA,MD 20892, USA. RI Quinn, Thomas/A-2494-2010 NR 167 TC 192 Z9 197 U1 2 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 1 PY 1992 VL 116 IS 1 BP 63 EP 77 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA GX157 UT WOS:A1992GX15700011 PM 1463471 ER PT J AU FAUCI, AS AF FAUCI, AS TI COMBINATION THERAPY FOR HIV-INFECTION - GETTING CLOSER SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material DE HIV INFECTIONS; ZIDOVUDINE; DIDEOXYCYTIDINE; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG THERAPY, COMBINATION ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; AIDS-RELATED COMPLEX; PHASE-I TRIAL; 2',3'-DIDEOXYINOSINE DDI; INTERFERON-ALPHA; KAPOSI-SARCOMA; ZIDOVUDINE; VIRUS AB Persons infected with the human immunodeficiency virus (HIV), their health care providers, and clinical investigators have recently expressed considerable interest in combination drug therapy. In this issue of Annals, Meng and associates report an added benefit from a regimen containing zidovudine and dideoxycytidine. Although these results are encouraging, the study sample is small and further investigation is necessary to confirm the observed benefit. RP FAUCI, AS (reprint author), NIAID,BLDG 31,ROOM 7A03,BETHESDA,MD 20892, USA. NR 15 TC 8 Z9 8 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 JAN 1 PY 1992 VL 116 IS 1 BP 85 EP 86 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA GX157 UT WOS:A1992GX15700013 PM 1309202 ER PT J AU LEYLANDJONES, B DAVIES, BR CLAGETTCARR, K SHOEMAKER, D MACFARLANE, D FORTNER, C ODWYER, PJ SAROSY, G FOSTER, BJ CHUN, HG HOTH, DF RUBINSTEIN, LV AF LEYLANDJONES, B DAVIES, BR CLAGETTCARR, K SHOEMAKER, D MACFARLANE, D FORTNER, C ODWYER, PJ SAROSY, G FOSTER, BJ CHUN, HG HOTH, DF RUBINSTEIN, LV TI PATIENT TREATMENT ON A COMPASSIONATE BASIS - DOCUMENTATION OF HIGH ADVERSE DRUG REACTION-RATE SO ANNALS OF ONCOLOGY LA English DT Article DE CLINICAL TRIALS; COMPASSIONATE IND; SPECIAL EXCEPTION PROTOCOLS; ADVERSE DRUG REACTIONS AB The special exception mechanism was established by the Division of Cancer Treatment (DCT), National Cancer Institute (NCI), for the provision of anticancer drugs not yet approved by the Food and Drug Administration (FDA) to patients on a compassionate basis. Strict guidelines have been established for the distribution of drugs through this mechanism and for the reporting of adverse drug reactions (ADRs) with investigational drugs. These guidelines have been used to format the data base which is maintained on all ADRs submitted by investigators. In this paper, the incidence of ADRs with the eleven investigational drugs most frequently administered on special exception protocols was determined for a twelve month time period, January 1, 1985 through December 31, 1985. On special exception protocols, the overall incidence rate of ADRs was significantly greater than that seen on research protocols for the time period. For three drugs, Methyl-G, DBD, and AMSA, the ADR incidence rate was seven to fifteen-fold greater on special exception protocols than on research protocols. In an analysis of all ADRs submitted to the FDA for the twelve months time period, no difference was found in the frequency of distribution of either types of adverse effects or the causal assessments of ADRs on special exception and research protocols. C1 NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,INVEST DRUG BRANCH,BETHESDA,MD 20892. DEPT ONCOL,MONTREAL H2W 1S6,QUEBEC,CANADA. NR 2 TC 2 Z9 2 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 JAN PY 1992 VL 3 IS 1 BP 59 EP 62 PG 4 WC Oncology SC Oncology GA HC082 UT WOS:A1992HC08200015 PM 1606071 ER PT J AU NORTON, JA DOPPMAN, JL JENSEN, RT AF NORTON, JA DOPPMAN, JL JENSEN, RT TI CURATIVE RESECTION IN ZOLLINGER-ELLISON SYNDROME - RESULTS OF A 10-YEAR PROSPECTIVE-STUDY SO ANNALS OF SURGERY LA English DT Article ID ISLET-CELL TUMORS; GASTRIC HYPERSECRETORY STATES; MULTIPLE ENDOCRINE NEOPLASIA; SECRETIN INJECTION TEST; LOCALIZING INSULINOMAS; ACID HYPERSECRETION; MANAGEMENT; LOCALIZATION; SURGERY; OMEPRAZOLE AB Since 1980, 73 patients with Zollinger-Ellison syndrome (ZES) without radiographic evidence of liver metastases were studied on a prospective protocol including medical management of gastric acid hypersecretion, extensive radiographic tumor localization, and exploratory surgery to find and resect gastrinoma for potential cure. Each patient had gastric acid hypersecretion effectively controlled with either H-2-blockers or omeprazole. Patients were divided prospectively into two groups, with all patients undergoing the same preoperative localization studies and extensive laparotomy. In contrast to group 1 (1980-1986) (36 patients), group 2 (1987-Oct. 1990) (37 patients) also underwent additional procedures (transillumination and duodenotomy) at surgery to find duodenal gastrinomas. Preoperative imaging studies localized tumor in 38 (52%) patients, and portal venous sampling for gastrin determinations was positive in 49 (67%) patients. Gastrinomas were found and resected in 57 (78%) patients. Significantly more gastrinomas (92% of patients) were found in group 2 than in group 1 patients (64%) (p < 0.01). This increase was due to increased numbers of duodenal gastrinomas in group 2 than in group 1 patients (43% versus 11%; p < 0.01). The increased ability to find duodenal gastrinomas did not significantly improve the immediate disease-free rate, which was 58% for all patients. Duodenal primary gastrinomas were found to have a significantly greater incidence of metastases (55%) and a significantly shorter disease-free interval (12 months) than pancreatic gastrinomas (22% and 84 months, respectively) suggesting that duodenal gastrinomas may be more malignant and not more frequently curable than pancreatic gastrinomas. Operations were performed with no deaths and 11% morbidity rate. Long-term follow-up showed that 50% of patients initially rendered disease free would develop recurrent disease by 5 years. Survival was excellent for all patients, and none died of malignant spread of the tumor or uncontrolled peptic ulcer disease, with a mean follow-up of 5 years. This finding is in contrast to patients who presented with metastatic disease on imaging studies and had a 20% 5-year survival rate. This study suggests that all patients with localized sporadic ZES can have the gastric acid hypersecretion managed medically, that overall survival of these patients is excellent, most (78%) can have all gastrinoma found and resected, and some (30%) will be cured (long-term disease-free survival). C1 NIAID,CTR CLIN,DEPT RADIOL,BETHESDA,MD 20892. NIAID,DIGEST DIS BRANCH,BETHESDA,MD 20892. RP NORTON, JA (reprint author), NCI,SURG BRANCH,SURG METAB SECT,BLDG 10,ROOM 2B07,BETHESDA,MD 20892, USA. NR 74 TC 177 Z9 180 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JAN PY 1992 VL 215 IS 1 BP 8 EP 18 PG 11 WC Surgery SC Surgery GA GY757 UT WOS:A1992GY75700003 PM 1531004 ER PT J AU PASTAN, I CHAUDHARY, V FITZGERALD, DJ AF PASTAN, I CHAUDHARY, V FITZGERALD, DJ TI RECOMBINANT TOXINS AS NOVEL THERAPEUTIC AGENTS SO ANNUAL REVIEW OF BIOCHEMISTRY LA English DT Review DE IMMUNOTOXIN; CANCER; RICIN; PSEUDOMONAS EXOTOXIN; DIPHTHERIA TOXIN ID RICIN-A-CHAIN; EPIDERMAL GROWTH-FACTOR; AERUGINOSA EXOTOXIN-A; HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN OVARIAN-CANCER; NUDE-MOUSE MODEL; INTERLEUKIN-2 FUSION PROTEIN; CARDIAC ALLOGRAFT SURVIVAL; ELONGATION FACTOR-II; AMINO-ACID-SEQUENCE RP PASTAN, I (reprint author), NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 159 TC 309 Z9 330 U1 4 U2 10 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4154 J9 ANNU REV BIOCHEM JI Annu. Rev. Biochem. PY 1992 VL 61 BP 331 EP 354 PG 24 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JE315 UT WOS:A1992JE31500014 PM 1497314 ER PT J AU THOMPSON, J DONKERSLOOT, JA AF THOMPSON, J DONKERSLOOT, JA TI N-(CARBOXYALKYL)AMINO ACIDS - OCCURRENCE, SYNTHESIS, AND FUNCTIONS SO ANNUAL REVIEW OF BIOCHEMISTRY LA English DT Review DE OPINES; PYRUVATE, OXIDOREDUCTASE; CROWN GALL; NAD(P)-BINDING DOMAINS; AMINO ACID DEHYDROGENASE ID CROWN-GALL TUMORS; ANGIOTENSIN-CONVERTING ENZYME; COMPLETE NUCLEOTIDE-SEQUENCE; N-EPSILON-CARBOXYMETHYLLYSINE; SUCROSE-FERMENTING ABILITY; NOPALINE SYNTHASE PROMOTER; AGROBACTERIUM-TUMEFACIENS STRAINS; BRADYKININ-POTENTIATING PEPTIDES; LACTATE-DEHYDROGENASE FRAMEWORK; GAS-LIQUID-CHROMATOGRAPHY RP THOMPSON, J (reprint author), NIDR, MICROBIAL ECOL LAB, BETHESDA, MD 20892 USA. NR 303 TC 29 Z9 30 U1 1 U2 5 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4154 EI 1545-4509 J9 ANNU REV BIOCHEM JI Annu. Rev. Biochem. PY 1992 VL 61 BP 517 EP 557 PG 41 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JE315 UT WOS:A1992JE31500020 PM 1497319 ER PT J AU MIZUUCHI, K AF MIZUUCHI, K TI TRANSPOSITIONAL RECOMBINATION - MECHANISTIC INSIGHTS FROM STUDIES OF MU AND OTHER ELEMENTS SO ANNUAL REVIEW OF BIOCHEMISTRY LA English DT Review DE GENOME REARRANGEMENT; DNA TRANSPOSITION; RETROVIRAL DNA INTEGRATION; TN10; TN7 ID INTEGRATION HOST FACTOR; SITE-SPECIFIC RECOMBINATION; STRAND-TRANSFER-REACTION; IMMUNODEFICIENCY-VIRUS INTEGRATION; ESCHERICHIA-COLI CHROMOSOME; RETROVIRAL DNA INTEGRATION; BINDING PROTEIN HU; BACTERIOPHAGE-MU; TN7 TRANSPOSITION; PHAGE-MU RP MIZUUCHI, K (reprint author), NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 162 TC 324 Z9 329 U1 2 U2 8 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4154 J9 ANNU REV BIOCHEM JI Annu. Rev. Biochem. PY 1992 VL 61 BP 1011 EP 1051 PG 41 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JE315 UT WOS:A1992JE31500032 PM 1323232 ER PT J AU WHITCOMB, JM HUGHES, SH AF WHITCOMB, JM HUGHES, SH TI RETROVIRAL REVERSE TRANSCRIPTION AND INTEGRATION - PROGRESS AND PROBLEMS SO ANNUAL REVIEW OF CELL BIOLOGY LA English DT Review DE RETROVIRAL RECOMBINATION; RETROVIRAL EVOLUTION; RETROVIRAL ONCOGENE ACTIVATION ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; ROUS-SARCOMA VIRUS; RNASE-H ACTIVITY; TRYPTOPHAN TRANSFER-RNA; FV-1 HOST RANGE; PLUS-STRAND DNA; VIRAL-DNA; RIBONUCLEASE-H; AVIAN-MYELOBLASTOSIS RP WHITCOMB, JM (reprint author), NCI, FREDERICK CANC RES & DEV CTR, ABL, BASIC RES PROGRAM, POB B, FREDERICK, MD 21702 USA. FU NCI NIH HHS [O1-CO-74101] NR 147 TC 180 Z9 181 U1 1 U2 6 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0743-4634 J9 ANNU REV CELL BIOL JI Annu. Rev. Cell Biol. PY 1992 VL 8 BP 275 EP 306 PG 32 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology GA JZ402 UT WOS:A1992JZ40200010 PM 1282352 ER PT J AU GELLERT, M AF GELLERT, M TI MOLECULAR ANALYSIS OF V(D)J RECOMBINATION SO ANNUAL REVIEW OF GENETICS LA English DT Review ID PRE-B-CELLS; SITE-SPECIFIC RECOMBINATION; COMBINED IMMUNE-DEFICIENCY; VARIABLE GENE SEGMENT; CONSTANT REGION GENE; LIGHT-CHAIN GENES; SIGNAL SEQUENCES; IMMUNOGLOBULIN GENES; RECEPTOR GENES; SCID MUTATION RP GELLERT, M (reprint author), NIDDKD, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. NR 86 TC 31 Z9 31 U1 0 U2 6 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4197 J9 ANNU REV GENET JI Annu. Rev. Genet. PY 1992 VL 26 BP 425 EP 446 PG 22 WC Genetics & Heredity SC Genetics & Heredity GA KD974 UT WOS:A1992KD97400017 PM 1482120 ER PT J AU BAKER, TA WICKNER, SH AF BAKER, TA WICKNER, SH TI GENETICS AND ENZYMOLOGY OF DNA-REPLICATION IN ESCHERICHIA-COLI SO ANNUAL REVIEW OF GENETICS LA English DT Review DE DNA REPLICATION; ORIC; PHAGE-LAMBDA; PLASMIDPL; COLEL ID POLYMERASE-III HOLOENZYME; HEAT-SHOCK PROTEINS; P1 PLASMID REPLICATION; SPECIALIZED NUCLEOPROTEIN STRUCTURES; BACTERIOPHAGE-LAMBDA; ENZYMATIC REPLICATION; CHROMOSOMAL ORIGIN; TRANSCRIPTIONAL ACTIVATION; TERMINUS REGION; BINDING-PROTEIN C1 NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. RP BAKER, TA (reprint author), NIDDK,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 183 TC 50 Z9 50 U1 0 U2 1 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4197 J9 ANNU REV GENET JI Annu. Rev. Genet. PY 1992 VL 26 BP 447 EP 477 PG 31 WC Genetics & Heredity SC Genetics & Heredity GA KD974 UT WOS:A1992KD97400018 PM 1482121 ER PT J AU FORNACE, AJ AF FORNACE, AJ TI MAMMALIAN GENES INDUCED BY RADIATION - ACTIVATION OF GENES ASSOCIATED WITH GROWTH-CONTROL SO ANNUAL REVIEW OF GENETICS LA English DT Review DE DNA DAMAGE; GROWTH-ARREST GENES; IMMEDIATE EARLY GENES; C14COS C14COS MOUSE MUTANT ID DNA-DAMAGING AGENTS; PROTEIN-KINASE-C; LEUKEMIA INHIBITORY FACTOR; IMMEDIATE EARLY RESPONSE; HAMSTER OVARY CELLS; IONIZING-RADIATION; UV-IRRADIATION; MESSENGER-RNA; HEAT-SHOCK; TRANSCRIPTION FACTOR RP FORNACE, AJ (reprint author), NCI,DCT,DTP,MOLEC PHARMACOL LAB,BETHESDA,MD 20892, USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 94 TC 285 Z9 286 U1 0 U2 2 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4197 J9 ANNU REV GENET JI Annu. Rev. Genet. PY 1992 VL 26 BP 507 EP 526 PG 20 WC Genetics & Heredity SC Genetics & Heredity GA KD974 UT WOS:A1992KD97400020 PM 1482123 ER PT J AU ROSENBERG, AS SINGER, A AF ROSENBERG, AS SINGER, A TI CELLULAR BASIS OF SKIN ALLOGRAFT-REJECTION - AN INVIVO MODEL OF IMMUNE-MEDIATED TISSUE DESTRUCTION SO ANNUAL REVIEW OF IMMUNOLOGY LA English DT Review DE TRANSPLANTATION; HISTOCOMPATIBILITY; T-CELLS; TOLERANCE; ALLOANTIGENS ID CYTO-TOXIC LYMPHOCYTES; MAJOR HISTOCOMPATIBILITY COMPLEX; EPIDERMAL LANGERHANS CELLS; HELPER T-CELLS; SPONGE MATRIX ALLOGRAFTS; CLASS-I MHC; MULTIVALENT CROSS-LINKING; GRAFT-REJECTION; DENDRITIC CELLS; TOLERANCE INDUCTION AB Rejection of transplanted tissue allografts results from T-cell recognition of histocompatibility antigens expressed by cells of the donor graft. This review focuses on the phenotype, specificity, and function of the T cells mediating rejection responses against skin allografts, and on the immune mechanisms by which host T cells are either activated or rendered non-responsive by cellular populations within the graft. We review the cellular basis for rejection responses across limited class-I and class-II major histocompatibility differences, as well as the specificity of the rejection response itself. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RP ROSENBERG, AS (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892, USA. NR 138 TC 243 Z9 246 U1 0 U2 9 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0732-0582 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 1992 VL 10 BP 333 EP 358 DI 10.1146/annurev.immunol.10.1.333 PG 26 WC Immunology SC Immunology GA HN012 UT WOS:A1992HN01200013 PM 1590990 ER PT J AU SHER, A COFFMAN, RL AF SHER, A COFFMAN, RL TI REGULATION OF IMMUNITY TO PARASITES BY T-CELLS AND T-CELL DERIVED CYTOKINES SO ANNUAL REVIEW OF IMMUNOLOGY LA English DT Review DE PARASITIC PROTOZOA AND HELMINTHS; CD4+ LYMPHOCYTE-TSUBSETS; CD8+ LYMPHOCYTES-T; CYTOKINES; IMMUNOREGULATION; CROSSREGULATION ID TUMOR-NECROSIS-FACTOR; PLASMODIUM-CHABAUDI-ADAMI; SCHISTOSOMA-MANSONI INFECTION; HYPERSENSITIVITY GRANULOMA-FORMATION; EXPERIMENTAL CEREBRAL MALARIA; ATHYMIC NUDE-MICE; INTERFERON-GAMMA; CUTANEOUS LEISHMANIASIS; MONOCLONAL-ANTIBODY; TRYPANOSOMA-CRUZI AB Parasitic protozoa and helminths are a diverse group of organisms which together form a major cause of infectious disease in humans and livestock. Studies in animal models have revealed that T lymphocytes and the cytokines they produce play a crucial role in determining the outcome of parasitic infection in terms of both protective immunity and immunopathology. Of particular interest is recent evidence that different parasitic infections in the context of different host genetic background can trigger polarized CD4+ T cell subset responses. The set of cytokines produced by these different T helper responses, in turn, can have opposing effects on the parasite, resulting in either control of infection or promotion of disease. Moreover, cytokines produced by one CD4+ subset can block either the production and/or activity of the cytokines produced by the other subset. The establishment of this state of cross-regulation may be important for parasite survival. CD8+ T cells also appear to play a dual effector/regulatory role in parasite immunity and immunopathology, although the mechanisms underlying their induction and function are less well understood. CD8+-mediated cytolytic killing functions have now been demonstrated against a number of different intracellular protozoa, although IFN-gamma produced by the same effector cells may also be critical in host community. In addition to providing highly relevant models for studying the selection and immunobiologic function of T-cell subsets, research on T lymphocyte-parasite interactions is crucial for the design of effective vaccines and immunotherapies and thus has broad practical as well as theoretical ramifications. C1 DNAX RES INST MOLEC & CELLULAR BIOL INC,DEPT IMMUNOL,PALO ALTO,CA 94304. RP SHER, A (reprint author), NIAID,PARASIT DIS LAB,IMMUNOL & CELL BIOL SECT,BETHESDA,MD 20892, USA. NR 135 TC 811 Z9 821 U1 6 U2 38 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0732-0582 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 1992 VL 10 BP 385 EP 409 DI 10.1146/annurev.immunol.10.1.385 PG 25 WC Immunology SC Immunology GA HN012 UT WOS:A1992HN01200015 PM 1590992 ER PT J AU WALDMANN, TA AF WALDMANN, TA TI IMMUNE RECEPTORS - TARGETS FOR THERAPY OF LEUKEMIA LYMPHOMA, AUTOIMMUNE-DISEASES AND FOR THE PREVENTION OF ALLOGRAFT-REJECTION SO ANNUAL REVIEW OF IMMUNOLOGY LA English DT Review DE CHIMERIC ANTIBODIES; INTERLEUKIN-2 RECEPTORS; IMMUNOTOXINS; IL-1 RECEPTOR ANTAGONIST; T-CELL ANTIGEN RECEPTOR ID ANTIGEN-BINDING SPECIFICITY; RECOMBINANT FUSION PROTEIN; CYTO-TOXIC ACTIVITY; T-CELL RECEPTORS; MONOCLONAL-ANTIBODY; PSEUDOMONAS EXOTOXIN; INTERLEUKIN-1 RECEPTOR; GROWTH-FACTOR; EFFECTOR FUNCTIONS; HUMANIZED ANTIBODY AB Immune receptor-directed therapy has been applied clinically to an array of human disorders. However, effective therapy using unmodified murine monoclonal antibodies was elusive because these antibodies are immunogenic and elicit a human immune response, are not cytocidal against human cells, and in most cases are not directed against a cell surface structure required for proliferation and survival. Recently therapy mediated by monoclonal antibodies has been revolutionized by the definition of cell surface structures as targets for effective monoclonal antibody action, the creation by genetic engineering of less immunogenic and more effective monoclonal antibodies, and by the arming of such antibodies with toxins and radionuclides. Furthermore, other therapeutic agents directed toward immune receptors have been developed, including cytokine-toxin fusion proteins as alternative vehicles to address abnormal receptor-expressing cells, soluble immune receptors and naturally occurring receptor antagonists as immunomodulators, and T cell antigen receptor peptides as immunogens to provide protection against autoimmune diseases. Thus, the new insights concerning the structure and function of lymphocyte cell surface receptors and the development of different modalities of receptor-specific therapy are providing new perspectives for the treatment of human leukemia/lymphoma, autoimmune and graft-vs-host diseases, and for the prevention of allograft rejection. RP WALDMANN, TA (reprint author), NCI,METAB BRANCH,BETHESDA,MD 20892, USA. NR 131 TC 37 Z9 37 U1 0 U2 0 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0732-0582 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 1992 VL 10 BP 675 EP 704 DI 10.1146/annurev.immunol.10.1.675 PG 30 WC Immunology SC Immunology GA HN012 UT WOS:A1992HN01200024 PM 1590999 ER PT J AU OTTESEN, EA NUTMAN, TB AF OTTESEN, EA NUTMAN, TB TI TROPICAL PULMONARY EOSINOPHILIA SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE FILARIASIS; PIE; ALVEOLITIS; FIBROSIS; WUCHERERIA-BANCROFTI; BRUGIA-MALAYI ID LOWER RESPIRATORY-TRACT; LUNG; DIETHYLCARBAMAZINE; DISORDERS; CELLS AB Tropical pulmonary eosinophilia is one of the many PIE syndromes [pulmonary infiltrates with eosinophilia (of the peripheral blood)]. It is caused by immunologic hyperresponsiveness to the filarial parasites Wuchereria bancrofti or Brugia malayi. Its clinical presentation incudes nocturnal cough, dyspnea, wheezing, fever, weight loss, fatigue, interstitial mottling on chest radiograph, predominantly restrictive but also obstructive lung function abnormalities, and peripheral blood eosinophilia of more than 3000 per-mu-l. It can be distinguished from other PIE syndromes by the patient's history of residence in the tropics, by the presence of extraordinarily high levels of both serum IgE and antifilarial antibodies, and by the dramatic clinical improvement after treatment with the antifilarial drug diethylcarbamazine. Recent studies indicate that the compromised lung diffusion capacity of patients with acute tropical pulmonary eosinophilia is a function of the degree of the eosinophilic alveolitis present and that, despite a 3-week course of diethylcarbamazine, low-grade alveolitis persists in almost half of such patients; this persistent alveolitis is likely to be the cause of the progressive interstitial fibrosis seen in many untreated or inadequately treated patients with tropical pulmonary eosinophilia. RP OTTESEN, EA (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. NR 39 TC 70 Z9 70 U1 1 U2 4 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 1992 VL 43 BP 417 EP 424 DI 10.1146/annurev.med.43.1.417 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA HL709 UT WOS:A1992HL70900033 PM 1580599 ER PT J AU STRAUS, SE AF STRAUS, SE TI ACUTE PROGRESSIVE EPSTEIN-BARR-VIRUS INFECTIONS SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE IMMUNODEFICIENCY; LYMPHOPROLIFERATIVE DISORDERS; TRANSPLANT COMPLICATIONS; AIDS; DIAGNOSIS ID LINKED LYMPHOPROLIFERATIVE SYNDROME; BONE-MARROW TRANSPLANTATION; VARIABLE PHENOTYPIC-EXPRESSION; CENTRAL NERVOUS-SYSTEM; B-CELL PROLIFERATIONS; APLASTIC-ANEMIA; IMMUNODEFICIENT PATIENTS; ANTIVIRAL CHEMOTHERAPY; MALIGNANT-LYMPHOMA; DNA HYBRIDIZATION AB A few Epstein-Barr virus (EBV) infections result in progressive, potentially fatal disease. Nearly all of these progressive EBV infections occur in individuals known or suspected to be immunodeficient. Diagnosis and treatment are difficult. RP STRAUS, SE (reprint author), NIAID,CLIN INVEST LAB,MED VIROL SECT,BETHESDA,MD 20892, USA. NR 71 TC 14 Z9 14 U1 0 U2 0 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 1992 VL 43 BP 437 EP 447 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA HL709 UT WOS:A1992HL70900035 PM 1316095 ER PT J AU STAMATOYANNOPOULOS, JA NIENHUIS, AW AF STAMATOYANNOPOULOS, JA NIENHUIS, AW TI THERAPEUTIC APPROACHES TO HEMOGLOBIN SWITCHING IN TREATMENT OF HEMOGLOBINOPATHIES SO ANNUAL REVIEW OF MEDICINE LA English DT Review ID BETA-GLOBIN GENE; SICKLE-CELL DISEASE; DOMINANT CONTROL REGION; ERYTHROID TRANSCRIPTION FACTOR; STIMULATES FETAL HEMOGLOBIN; TRANSGENIC MICE; DNA METHYLATION; GAMMA-GLOBIN; F-CELLS; HB-F AB The past decade has witnessed profound increases in knowledge of the structure, function, and developmental regulation of the human globin genes. This information has deepened our understanding of the molecular and cellular mechanisms underlying inherited disorders affecting hemoglobin, and it has provided a new perspective for attaining meaningful increases in fetal hemoglobin synthesis in the management of sickle cell anemia and beta thalassemia. Efforts to provide therapy for these disorders are based on three factors: an understanding of their pathophysiology; the potential for fetal hemoglobin to alter its manifestation; and the concept that developmental changes in globin gene expression might be reversed by manipulating cellular and molecular regulatory mechanisms. In this review we discuss these topics and examine critically recent efforts to apply various pharmacological agents to in vitro, animal, and human models with the goal of increasing HbF synthesis. Several agents have demonstrated activity in patients with hemoglobin disorders. One such agent, hydroxyurea, has been shown to be potentially efficacious in phase II clinical trials in patients with sickle cell anemia and awaits testing in a placebo-controlled phase III study. C1 NHLBI, CLIN HEMATOL BRANCH, BETHESDA, MD 20892 USA. RP STAMATOYANNOPOULOS, JA (reprint author), UNIV WASHINGTON, SCH MED, SEATTLE, WA 98195 USA. NR 137 TC 60 Z9 61 U1 0 U2 1 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 1992 VL 43 BP 497 EP 521 PG 25 WC Medicine, General & Internal SC General & Internal Medicine GA HL709 UT WOS:A1992HL70900039 PM 1374600 ER PT J AU WICKNER, RB AF WICKNER, RB TI DOUBLE-STRANDED AND SINGLE-STRANDED RNA VIRUSES OF SACCHAROMYCES-CEREVISIAE SO ANNUAL REVIEW OF MICROBIOLOGY LA English DT Review DE RIBOSOMAL FRAMESHIFTING; REPLICATION INVITRO; PACKAGING SITE; KEX GENES; N-ACETYLTRANSFERASE; KILLER TOXIN ID CAPSID PROTEIN VP4; K1 KILLER TOXIN; L-A; ALPHA-FACTOR; YEAST VIRUS; MITOCHONDRIAL NUCLEASE; SUPERKILLER MUTATIONS; CHROMOSOMAL GENE; CYTO-PATHOLOGY; MESSENGER-RNAS AB Yeast RNA viruses include L-A (and its toxin-encoding satellites M1, M2,. . .) and L-BC dsRNA viruses and the single-stranded replicons 20S RNA and 23S RNA. L-A has a single-segment 4.6-kb linear genome encoding a major coat protein (gag) and its RNA-dependent RNA polymerase (pol), the latter expressed as a gag-pol fusion protein formed by a -1 ribosomal frameshift. In vitro replication, transcription, and binding systems for L-A have been used to define cis sites necessary for packaging and replication of viral RNA. Cellular functions that promote viral replication include the MAK3-encoded N-acetyltransferase whose modification of the gag N terminus is necessary for L-A virus assembly. The toxins encoded by the M satellite RNAs are processed by enzymes (KEX1 and KEX2, for killer expression) whose study led to discovery of mammalian hormone-processing enzymes. 20S RNA is an apparently naked circular RNA replicon (with a dsRNA form called W) encoding a RNA polymerase-like molecule. Its copy number is induced 10,000-fold in 1% potassium acetate, and it is subject to the same SKI antiviral system that represses L-A, L-BC, and M dsRNA copy number. RP WICKNER, RB (reprint author), NIDDKD,GENET SIMPLE EUKARYOTES SECT,BIOCHEM PHARMACOL LAB,BETHESDA,MD 20892, USA. NR 142 TC 89 Z9 92 U1 0 U2 8 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4227 J9 ANNU REV MICROBIOL JI Annu. Rev. Microbiol. PY 1992 VL 46 BP 347 EP 375 DI 10.1146/annurev.micro.46.1.347 PG 29 WC Microbiology SC Microbiology GA JQ929 UT WOS:A1992JQ92900013 PM 1444259 ER PT J AU ZIMMER, A AF ZIMMER, A TI MANIPULATING THE GENOME BY HOMOLOGOUS RECOMBINATION IN EMBRYONIC STEM-CELLS SO ANNUAL REVIEW OF NEUROSCIENCE LA English DT Review DE GENE TARGETING; CHIMERIC MICE; DEVELOPMENT ID GERM-LINE TRANSMISSION; PROTO-ONCOGENE INT-1; LESCH-NYHAN SYNDROME; CULTURED MAMMALIAN-CELLS; II MESSENGER-RNA; MOUSE EMBRYOS; HPRT GENE; T-CELLS; HISTOCHEMICAL-LOCALIZATION; BRAIN-DEVELOPMENT RP ZIMMER, A (reprint author), NIMH,CELL BIOL LAB,DEV BIOL UNIT,BETHESDA,MD 20892, USA. RI Zimmer, Andreas/B-8357-2009 NR 94 TC 49 Z9 49 U1 0 U2 0 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0147-006X J9 ANNU REV NEUROSCI JI Annu. Rev. Neurosci. PY 1992 VL 15 BP 115 EP 137 DI 10.1146/annurev.neuro.15.1.115 PG 23 WC Neurosciences SC Neurosciences & Neurology GA HF921 UT WOS:A1992HF92100005 PM 1575439 ER PT J AU GERFEN, CR AF GERFEN, CR TI THE NEOSTRIATAL MOSAIC - MULTIPLE LEVELS OF COMPARTMENTAL ORGANIZATION IN THE BASAL GANGLIA SO ANNUAL REVIEW OF NEUROSCIENCE LA English DT Review DE BASAL GANGLIA; STRIATUM; DOPAMINE RECEPTORS; PARKINSONS DISEASE ID LEUKOAGGLUTININ PHA-L; D1 DOPAMINE RECEPTOR; IDENTIFIED STRIATONIGRAL NEURONS; ELECTRON-MICROSCOPIC ANALYSIS; CALCIUM-BINDING PROTEIN; NIGRA PARS RETICULATA; SUBSTANCE-P RECEPTOR; RAT NEOSTRIATUM; CAUDATE-NUCLEUS; GENE-EXPRESSION RP GERFEN, CR (reprint author), NIMH,CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 144 TC 751 Z9 766 U1 1 U2 19 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0147-006X J9 ANNU REV NEUROSCI JI Annu. Rev. Neurosci. PY 1992 VL 15 BP 285 EP 320 DI 10.1146/annurev.neuro.15.1.285 PG 36 WC Neurosciences SC Neurosciences & Neurology GA HF921 UT WOS:A1992HF92100011 PM 1575444 ER PT J AU ALGER, JR FRANK, JA AF ALGER, JR FRANK, JA TI THE UTILIZATION OF MAGNETIC-RESONANCE-IMAGING IN PHYSIOLOGY SO ANNUAL REVIEW OF PHYSIOLOGY LA English DT Review DE ANATOMY; TISSUE FUNCTION; NONINVASIVE; CONTRAST AGENT; MRI ID SUPERPARAMAGNETIC IRON-OXIDE; INTRAVOXEL INCOHERENT MOTION; CEREBRAL BLOOD-FLOW; RABBIT TUMOR-MODEL; MR CONTRAST AGENT; GD-DTPA; GADOLINIUM-DTPA; CINE MR; BRAIN; DIFFUSION C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. RP ALGER, JR (reprint author), NINCDS,NEUROIMAGING BRANCH,BLDG 10,RM 1C-451,BETHESDA,MD 20892, USA. NR 94 TC 8 Z9 8 U1 0 U2 0 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0066-4278 J9 ANNU REV PHYSIOL JI Annu. Rev. Physiol. PY 1992 VL 54 BP 827 EP 846 DI 10.1146/annurev.physiol.54.1.827 PG 20 WC Physiology SC Physiology GA HJ056 UT WOS:A1992HJ05600042 PM 1562193 ER PT J AU QUINN, TC RUFF, A MODLIN, J AF QUINN, TC RUFF, A MODLIN, J TI HIV-INFECTION AND AIDS IN CHILDREN SO ANNUAL REVIEW OF PUBLIC HEALTH LA English DT Review DE PEDIATRICS; DIAGNOSIS; THERAPY; EPIDEMIOLOGY ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; PNEUMOCYSTIS-CARINII PNEUMONIA; SEXUALLY-TRANSMITTED DISEASES; INTRAVENOUS DRUG-USERS; PERINATAL TRANSMISSION; INFANTS BORN; VERTICAL TRANSMISSION; UNITED-STATES; SEROPOSITIVE MOTHERS C1 JOHNS HOPKINS UNIV,DEPT PEDIAT,BALTIMORE,MD 21205. JOHNS HOPKINS SCH PUBL HLTH & HYG,DEPT INT HLTH,BALTIMORE,MD 21205. NIAID,IMMUNOREGULAT LAB,BALTIMORE,MD 21205. RP QUINN, TC (reprint author), JOHNS HOPKINS UNIV,DEPT MED,BALTIMORE,MD 21205, USA. NR 163 TC 8 Z9 8 U1 1 U2 1 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 SN 0163-7525 J9 ANNU REV PUBL HEALTH JI Annu. Rev. Public Health PY 1992 VL 13 BP 1 EP 30 PG 30 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA HT577 UT WOS:A1992HT57700001 PM 1599581 ER PT S AU NECKERS, L ROSOLEN, A FAHMY, B WHITESELL, L AF NECKERS, L ROSOLEN, A FAHMY, B WHITESELL, L BE Baserga, R Denhardt, DT TI SPECIFIC-INHIBITION OF ONCOGENE EXPRESSION INVITRO AND INVIVO BY ANTISENSE OLIGONUCLEOTIDES SO ANTISENSE STRATEGIES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Proceedings Paper CT CONF ON ANTISENSE STRATEGIES CY JAN 12-15, 1992 CL PHILADELPHIA, PA SP NEW YORK ACAD SCI, GLAXO RES LABS, THOMAS JEFFERSON UNIV, JEFFERSON MED COLL, ABBOTT LABS, AMER CYANAMID, BIO ONE HUNDRED ONE, BURROUGHS WELLCOME, HOFFMANN LAROCHE, LILLY RES LABS, MERCK SHARP & DOHME RES LABS RP NECKERS, L (reprint author), NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA NEW YORK SN 0077-8923 BN 0-89766-747-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1992 VL 660 BP 37 EP 44 DI 10.1111/j.1749-6632.1992.tb21055.x PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA BX23J UT WOS:A1992BX23J00004 PM 1340154 ER PT B AU DICHEK, DA AF DICHEK, DA BE ZILLA, P FASOL, R CALLOW, A TI THERAPEUTIC POTENTIAL OF GENETIC-ENGINEERING - ENHANCEMENT OF ENDOTHELIAL-CELL FIBRINOLYSIS SO APPLIED CARDIOVASCULAR BIOLOGY, 1990-91 SE INTERNATIONAL SOCIETY FOR APPLIED CARDIOVASCULAR BIOLOGY LA English DT Proceedings Paper CT 2ND ANNUAL MEETING OF THE INTERNATIONAL SOC FOR APPLIED CARDIOVASCULAR BIOLOGY CY SEP 17-20, 1990 CL VENICE, ITALY SP INT SOC APPL CARDIOVASC BIOL RP DICHEK, DA (reprint author), NHLBI,MOLEC HEMATOL BRANCH,BLDG 10,RM 7D-18,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA BASEL BN 3-8055-5430-3 J9 INT S APP C JI Int.Soc.Appl.Cardiovasc.Biol. PY 1992 VL 2 BP 197 EP 204 PG 8 WC Biology; Cardiac & Cardiovascular Systems; Medicine, General & Internal SC Life Sciences & Biomedicine - Other Topics; Cardiovascular System & Cardiology; General & Internal Medicine GA BV45N UT WOS:A1992BV45N00027 ER PT J AU STERNE, JAC KINGMAN, A LOE, H AF STERNE, JAC KINGMAN, A LOE, H TI ASSESSING THE NATURE OF PERIODONTAL-DISEASE PROGRESSION - AN APPLICATION OF COVARIANCE STRUCTURE ESTIMATION SO APPLIED STATISTICS-JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C LA English DT Article DE COVARIANCE STRUCTURES; GENERALIZED LEAST SQUARES; LONGITUDINAL DATA; PERIODONTAL DISEASE AB Differing theories of the nature of periodontal disease progression have been proposed, but there is no convincing statistical evidence with which to choose between them. Three models for disease progression are developed, and their covariance structures are derived and shown to be hierarchical. The estimation of the covariance structures of the three models is illustrated with both simulated data and data from a long-term study of periodontal disease progression. The study provides insight into both the nature of periodontal disease progression and the use of the estimation of covariance structural models to distinguish between models for which a likelihood is not completely specified. C1 NIH,BETHESDA,MD 20892. RP STERNE, JAC (reprint author), UNIV LONDON LONDON SCH HYG & TROP MED,MRC,DEPT EPIDEMIOL & POPULAT SCI,DENT RES UNIT,KEPPEL ST,LONDON WC1E 7HT,ENGLAND. NR 7 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD, OXON, ENGLAND OX4 1JF SN 0035-9254 J9 APPL STAT-J ROY ST C JI Appl. Stat.-J. R. Stat. Soc. PY 1992 VL 41 IS 3 BP 539 EP 552 DI 10.2307/2348088 PG 14 WC Statistics & Probability SC Mathematics GA HZ874 UT WOS:A1992HZ87400003 ER PT J AU ODONNELL, BP DAWSON, NA WEISS, RB MYERS, CE JAMES, WD AF ODONNELL, BP DAWSON, NA WEISS, RB MYERS, CE JAMES, WD TI SURAMIN-INDUCED SKIN REACTIONS SO ARCHIVES OF DERMATOLOGY LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; AIDS-RELATED COMPLEX; RED BLOOD-CELLS; ADRENOCORTICAL CARCINOMA; IMMUNE-RESPONSES; POROKERATOSIS; INVITRO; THERAPY; IMMUNOSUPPRESSION; KERATOACANTHOMA AB Background and Design.- Suramin sodium, a polysulfonated napthylurea, has been used for more than 70 years as a chemotherapeutic agent for a variety of diseases. In a phase II trial of suramin, 20 patients with metastatic prostate carcinoma refractory to hormonal manipulation were evaluated retrospectively for evidence of skin toxicity. Results.- Three types of skin reaction were noted: generalized, erythematous, maculopapular eruption (10 patients); keratoacanthoma (two patients); and disseminated superficial actinic porokeratosis (one patient). A total of 15 episodes of some form of skin reaction occurred in 13 patients. The maculopapular eruptions resolved in 3 to 5 days despite continued treatment with suramin. Conclusions.- Cutaneous toxicity was a frequent and, often, self-limited side effect of suramin therapy, occurring in 13 (65%) patients. Keratoacanthoma and disseminated superficial actinic porokeratosis have not previously been reported to occur with suramin therapy. The immunosuppressive effect of suramin may induce the keratoacanthoma and disseminated superficial actinic porokeratosis lesions. C1 WALTER REED ARMY MED CTR,MED ONCOL SECT,WASHINGTON,DC 20307. NCI,DIV CENT RES,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. WALTER REED ARMY MED CTR,DERMATOL SERV,WASHINGTON,DC 20307. WALTER REED ARMY MED CTR,HEMATOL ONCOL SERV,WASHINGTON,DC 20307. NR 38 TC 27 Z9 27 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JAN PY 1992 VL 128 IS 1 BP 75 EP 79 DI 10.1001/archderm.128.1.75 PG 5 WC Dermatology SC Dermatology GA GZ894 UT WOS:A1992GZ89400010 PM 1531404 ER PT J AU ALTEMUS, M PIGOTT, T KALOGERAS, KT DEMITRACK, M DUBBERT, B MURPHY, DL GOLD, PW AF ALTEMUS, M PIGOTT, T KALOGERAS, KT DEMITRACK, M DUBBERT, B MURPHY, DL GOLD, PW TI ABNORMALITIES IN THE REGULATION OF VASOPRESSIN AND CORTICOTROPIN RELEASING-FACTOR SECRETION IN OBSESSIVE-COMPULSIVE DISORDER SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Review ID FACTOR-LIKE IMMUNOREACTIVITY; CEREBROSPINAL-FLUID VASOPRESSIN; GLUCOSE METABOLIC RATES; CENTRAL NERVOUS-SYSTEM; ARGININE-VASOPRESSIN; ALZHEIMERS-DISEASE; NEUROHYPOPHYSEAL HORMONES; ANOREXIA-NERVOSA; DOPAMINE SYSTEMS; BRAIN-REGIONS AB In light of prior data that the central administration of vasopressin in animals is associated with abnormal persistence of behaviors acquired under aversive conditioning, we studied the secretion of arginine vasopressin into the cerebrospinal fluid and plasma in patients with obsessive-compulsive disorder and controls. Patients with obsessive-compulsive disorder had significantly elevated basal levels of arginine vasopressin in the cerebrospinal fluid and significantly increased secretion of arginine vasopressin into the plasma in response to hypertonic saline administration. Moreover, seven of 12 patients with obsessive-compulsive disorder showed a loss of the normal linear relationship between plasma arginine vasopressin level and osmolality. In addition, cerebrospinal fluid corticotropin releasing hormone, which has synergistic effects with arginine vasopressin centrally and at the pituitary gland, was also significantly elevated in patients with obsessive-compulsive disorder compared with controls. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. UNIV MICHIGAN,MED CTR,DEPT PSYCHIAT,ANN ARBOR,MI 48109. RP ALTEMUS, M (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,BLDG 10,ROOM 35231,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Demitrack, Mark/I-7697-2013 NR 114 TC 139 Z9 139 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JAN PY 1992 VL 49 IS 1 BP 9 EP 20 PG 12 WC Psychiatry SC Psychiatry GA GY800 UT WOS:A1992GY80000001 PM 1370198 ER PT J AU SWEDO, SE LEONARD, HL KRUESI, MJP RETTEW, DC LISTWAK, SJ BERRETTINI, W STIPETIC, M HAMBURGER, S GOLD, PW POTTER, WZ RAPOPORT, JL AF SWEDO, SE LEONARD, HL KRUESI, MJP RETTEW, DC LISTWAK, SJ BERRETTINI, W STIPETIC, M HAMBURGER, S GOLD, PW POTTER, WZ RAPOPORT, JL TI CEREBROSPINAL-FLUID NEUROCHEMISTRY IN CHILDREN AND ADOLESCENTS WITH OBSESSIVE-COMPULSIVE DISORDER SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID CLOMIPRAMINE TREATMENT; ELECTROCHEMICAL DETECTION; VASOPRESSIN-NEUROPHYSIN; TOURETTE SYNDROME; ANOREXIA-NERVOSA; DEPRESSION; PLASMA; CSF; SEROTONIN; OXYTOCIN AB Cerebrospinal fluid hormones, monoaminergic metabolites, and dynorphin A (1-8 sequence) were examined in 43 children with severe, primary obsessive-compulsive disorder. Cerebrospinal fluid levels of 5-hydroxyindoleacetic acid were positively correlated with one of eight obsessive-compulsive disorder severity ratings and three of seven measures of improvement following 5 weeks of treatment with clomipramine hydrochloride. Arginine vasopressin concentration was significantly and negatively correlated with several ratings of obsessive-compulsive disorder symptom severity, while oxytocin concentration was positively correlated with depressive symptoms. The ratio of arginine vasopressin to oxytocin was also negatively correlated with obsessive-compulsive disorder and depressive symptoms. Comorbid affective disorder was associated with decreased arginine vasopressin concentrations, while concomitant anxiety disorder was associated with increased oxytocin. Dynorphin A (1-8 sequence), homovanillic acid, corticotropin, 3-methoxy-4-hydroxyphenylglycol, and corticotropin releasing hormone were not significantly related to obsessive-compulsive disorder symptoms. These results seem to indicate that arginine vasopressin may be related to obsessive-compulsive disorder symptom severity, while 5-hydroxyindoleacetic acid might be associated with drug response. C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NIMH,CLIN NEUROGEN BRANCH,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,CLIN PHARMACOL SECT,BETHESDA,MD 20892. RP SWEDO, SE (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 72 TC 107 Z9 108 U1 0 U2 3 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 JAN PY 1992 VL 49 IS 1 BP 29 EP 36 PG 8 WC Psychiatry SC Psychiatry GA GY800 UT WOS:A1992GY80000003 PM 1370197 ER PT J AU ALEXANDER, RC SPECTOR, SA CASANOVA, MF KLEINMAN, J WYATT, RJ KIRCH, DG AF ALEXANDER, RC SPECTOR, SA CASANOVA, MF KLEINMAN, J WYATT, RJ KIRCH, DG TI SEARCH FOR CYTOMEGALOVIRUS IN THE POSTMORTEM BRAINS OF SCHIZOPHRENIC-PATIENTS USING THE POLYMERASE CHAIN-REACTION SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID HERPES-SIMPLEX VIRUS; CEREBROSPINAL-FLUID; ANTIBODY-TITERS; FOLLOW-UP; INFECTION; SEQUENCES; DNA; TISSUE; AMPLIFICATION; ABNORMALITIES AB Cytomegalovirus infection has a number of features that suggest a possible association between congenital infection and schizophrenia. Previous studies have investigated anticytomegalovirus antibody titers or attempted directly to identify viral antigens in body fluids or brain tissue from schizophrenic subjects but have been limited by the sensitivity of the available methods. The highly sensitive polymerase chain reaction, a newly developed technique for gene amplification, was used to search for cytomegalovirus in the DNA extracted from postmortem temporal cortex samples of eight schizophrenic subjects, eight nonschizophrenic suicide victims, and eight normal controls. Cytomegalovirus-specific DNA amplification was not detected in any of the samples. The implications of this finding for the viral hypothesis of schizophrenia are discussed. C1 ST ELIZABETH HOSP, NIMH, CTR NEUROSCI, NEUROSCI BRANCH, WASHINGTON, DC 20032 USA. UNIV CALIF SAN DIEGO, CTR MOLEC GENET, LA JOLLA, CA 92093 USA. ST ELIZABETH HOSP, NIMH, CTR NEUROSCI, CLIN BRAIN DISORDERS BRANCH, WASHINGTON, DC 20032 USA. UNIV CALIF SAN DIEGO, DEPT PEDIAT, LA JOLLA, CA 92093 USA. NR 61 TC 14 Z9 15 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JAN PY 1992 VL 49 IS 1 BP 47 EP 53 PG 7 WC Psychiatry SC Psychiatry GA GY800 UT WOS:A1992GY80000005 PM 1309417 ER PT J AU FRATICELLI, A ROSSI, L SOCILLO, AI BORIA, C CAPOGROSSI, MC PACIARONI, E AF FRATICELLI, A ROSSI, L SOCILLO, AI BORIA, C CAPOGROSSI, MC PACIARONI, E TI ENDOTHELIN-1 MAY ACT AS A NEGATIVE INOTROPIC AGENT IN CARDIAC MYOCYTES FROM YOUNG AND SENESCENT RATS SO ARCHIVES OF GERONTOLOGY AND GERIATRICS LA English DT Article; Proceedings Paper CT 4TH INTERNATIONAL CONGRESS OF THE INTERNATIONAL ASSOC BIOMEDICAL GERONTOLOGY CY JUN 26-29, 1991 CL ANCONA, ITALY SP INT ASSOC BIOMED GERONTOL DE ENDOTHELIN-1; CARDIAC MYOCYTES; NEGATIVE INOTROPISM; AGING ID SMOOTH-MUSCLE CELLS; PROTEIN KINASE-C; VENTRICULAR MYOCYTES; GUINEA-PIG; PHOSPHOINOSITIDE TURNOVER; PHORBOL ESTER; ATRIA; PHOSPHATIDYLINOSITOL; ACTIVATION; RESPONSES AB The contractile response to Endothelin-1 (ET-1 ) has been investigated in electrically stimulated single cardiac myocytes isolated from hearts of young and senescent rats. ET-1 (0.1-10 nM) exhibited a marked negative inotropic effect in both age groups. ET-1 (1.0 nM) also reduced the occurrence of spontaneous contractile oscillations in young myocytes, suggesting depletion of sarcoplasmic reticulum - Ca2+ stores. The possibility that ET-1 may have opposite effects on myocardial contractility is discussed. C1 IST NAZL RIPOSA & CURA ANZIANI,CTR SCI INFORMAT,I-60131 ANCONA,ITALY. NIA,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. RP FRATICELLI, A (reprint author), IST NAZL RIPOSA & CURA ANZIANI,EXPTL CARDIOL LAB,VIA MONTAGNOLA 164,I-60131 ANCONA,ITALY. NR 30 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI 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. PY 1992 SU 3 BP 151 EP 158 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA JM302 UT WOS:A1992JM30200015 ER PT J AU JIANG, BM TSUNEMITSU, H QIAN, Y GREEN, KY OSETO, M YAMASHITA, Y SAIF, LJ AF JIANG, BM TSUNEMITSU, H QIAN, Y GREEN, KY OSETO, M YAMASHITA, Y SAIF, LJ TI ANALYSIS OF THE GENETIC DIVERSITY OF GENE-5 AND GENE-6 AMONG GROUP-C ROTAVIRUSES USING CDNA PROBES SO ARCHIVES OF VIROLOGY LA English DT Article ID NORTHERN BLOT HYBRIDIZATION; GROUP-A ROTAVIRUSES; ANTIGENICALLY DISTINCT ROTAVIRUSES; MOLECULAR CHARACTERIZATION; PORCINE PARAROTAVIRUS; SERIAL PROPAGATION; SEQUENCE-ANALYSIS; GNOTOBIOTIC PIGS; CELL-LINE; VIRUS AB Two partial cDNA clones of genes 5 (encoding the major inner capsid protein VP 6) and 6 (encoding a nonstructural protein) of the porcine group (Gp) C rotavirus (Cowden strain) were radiolabeled with P-32 and used individually as probes in Northern and dot blot hybridization assays. The specificity of each probe was tested against genomic dsRNA from: (1) porcine Gp A, B, and C rotaviruses; (2) Gp C rotaviruses from different species; and (3) porcine Gp C rotavirus field strains with varying electropherotype patterns. Neither probe hybridized with ds RNA from the porcine Gp A and B strains under the stringency conditions employed in the study. However, the gene 5 probe hybridized with the corresponding gene from the homologous porcine and the heterologous human and bovine Gp C rotaviruses tested. The gene 6 probe hybridized with the corresponding gene from the homologous Cowden strain, but hybridized weakly with gene 6 from the human and bovine Gp C rotaviruses. Both probes recognized all six different porcine Gp C field strains, although with varying intensities. Our results demonstrate that the gene 5 and 6 probes used in this study are specific for Gp C rotaviruses. However, evidence for greater genetic variation in the gene 6 among porcine, bovine and human Gp C strains suggested that the gene 5 probe may prove more broadly reactive among Gp C strains from different species. cDNA probes used in our study should prove useful for the detection of Gp C rotaviruses in feces and facilitate epidemiologic studies. C1 OHIO STATE UNIV,OHIO AGR RES & DEV CTR,FOOD ANIM HLTH RES PROGRAM,1680 MADISON AVE,WOOSTER,OH 44691. NIH,INFECT DIS LAB,BETHESDA,MD 20892. EHIME PREFECTURAL INST PUBL HLTH,MATSUYAMA,EHIME,JAPAN. NR 39 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 1992 VL 126 IS 1-4 BP 45 EP 56 DI 10.1007/BF01309683 PG 12 WC Virology SC Virology GA JL666 UT WOS:A1992JL66600005 PM 1326268 ER PT J AU DIMARTINO, A SAFAR, J CERONI, M GIBBS, CJ AF DIMARTINO, A SAFAR, J CERONI, M GIBBS, CJ TI PURIFICATION OF NONINFECTIOUS GANGLIOSIDE PREPARATIONS FROM SCRAPIE-INFECTED BRAIN-TISSUE SO ARCHIVES OF VIROLOGY LA English DT Article ID CREUTZFELDT-JAKOB DISEASE; BOVINE SPONGIFORM ENCEPHALOPATHY; HUMAN GROWTH-HORMONE; AGENT; VIRUS; EPIDEMIOLOGY; INACTIVATION; PROTEIN; CATTLE AB The extraction and purification of gangliosides from brains of animals infected with the scrapie agent was evaluated by scaling-down a large-scale procedure currently used with bovine brains. Inactivation experiments employed hamster brains infected with the 263 K strain of scrapie. Residual infectivity was determined at different points of the procedure and in the final preparation by an in vivo animal bioassay. The efficacy of single steps, which included chemicals or physical techniques known to affect the viability of the scrapie agent, was verified by spiking experiments where known amounts of infectivity were added just before each single step. Infectivity was significantly diminished at early stages of the purification, and no infectivity was detected in the final preparation containing purified gangliosides. The significant reduction of infectivity at intermediate steps and the total absence of detectable infectivity in the final product confirmed that a combination of heat and exposure to sodium hydroxide, even in the presence of organic solvents, completely inactivated the scrapie agent. C1 NINCDS,CENT NERVOUS SYST STUDIES LAB,BLDG 36-4A15,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. RI Safar, Jiri/G-6512-2013; ceroni, mauro/G-7080-2011 OI ceroni, mauro/0000-0002-8947-5007 NR 34 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 1992 VL 124 IS 1-2 BP 111 EP 121 PG 11 WC Virology SC Virology GA HP113 UT WOS:A1992HP11300009 PM 1571012 ER PT J AU MAHNKE, C KASHAIYA, P ROSSLER, J BANNERT, H LEVIN, A BLATTNER, WA DIETRICH, M LUANDE, J LOCHELT, M FRIEDMANKIEN, AE KOMAROFF, AL LOH, PC WESTARP, ME FLUGEL, RM AF MAHNKE, C KASHAIYA, P ROSSLER, J BANNERT, H LEVIN, A BLATTNER, WA DIETRICH, M LUANDE, J LOCHELT, M FRIEDMANKIEN, AE KOMAROFF, AL LOH, PC WESTARP, ME FLUGEL, RM TI HUMAN SPUMAVIRUS ANTIBODIES IN SERA FROM AFRICAN PATIENTS SO ARCHIVES OF VIROLOGY LA English DT Article ID HUMAN SYNCYTIAL VIRUS; FOAMY VIRUS; HUMAN SPUMARETROVIRUS; PREVALENCE; DISEASE; GENES AB Serum samples collected from patients with a wide variety of diseases from African and other countries were tested for antibodies to the human spumaretrovirus (HSRV). A spumaviral env-specific ELISA was employed as screening test. Out of 3020 human sera screened, 106 were found to be positive (3.2%). While the majority of patients' sera from Europe (1581) were negative, 26 were positive (1.6%). Sera from healthy adult blood donors (609), from patients with multiple sclerosis (48), Graves' disease (45), and chronic fatigue syndrome (41) were negative or showed a very low prevalence for spumaviral env antibodies. A higher percentage of seropositives (6.3%) were found among 1338 African patients from Tanzania, Kenya, and Gabon. Out of 1180 patients from Tanzania, 708 suffered from tumors, 75 from AIDS, and 128 had gynecological problems; 51 of the Tanzanian patients were HSRV seropositive (4.3%). A particularly high percentage of 16.6% seropositives were identified among nasopharyngeal carcinoma patients (NPC) from Kenya and Tanzania consistent with results reported 10 years ago. However, 20 nasopharyngeal carcinoma patients from Malaysia were HSRV-seronegative. In selected cases, sera from seropositive individuals were reacted with proteins from HSRV-infected cells in vitro. HSRV env-and gag-specific antibodies were specifically detected by these sera in Western blots. The results indicate spumavirus infections in human patients with various diseases at a relatively low prevalence worldwide; in African patients, however, the prevalence of spumavirus infections is markedly higher. C1 DEUTSCH KREBSFORSCHUNGSZENTRUM,ANGEW TUMORVIROL,PROJEKTGRP HUMANE RETROVIREN,W-6900 HEIDELBERG,GERMANY. OCEAN RD HOSP,TANZANIA TUMORCTR,DAR ES SALAAM,TANZANIA. MRC,CLIN RES CTR,RTI UNIT,HARROW HA1 3UJ,MIDDX,ENGLAND. BERNHARD NOCHT INST TROPENMED,HAMBURG,GERMANY. NEW YORK MED CTR,NEW YORK,NY. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. NCI,BETHESDA,MD 20892. UNIV HAWAII MANOA,HONOLULU,HI 96822. UNIV ULM,REHABIL KRANKENHAUSES ULM,W-7900 ULM,GERMANY. FU NCI NIH HHS [N0I-CP-85603] NR 27 TC 34 Z9 34 U1 0 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 1992 VL 123 IS 3-4 BP 243 EP 253 DI 10.1007/BF01317261 PG 11 WC Virology SC Virology GA HM332 UT WOS:A1992HM33200001 PM 1314048 ER PT J AU CRISTIANO, K DIBISCEGLIE, AM HOOFNAGLE, JH FEINSTONE, SM AF CRISTIANO, K DIBISCEGLIE, AM HOOFNAGLE, JH FEINSTONE, SM TI HEPATITIS-C VIRAL-RNA IN SERUM OF PATIENTS WITH CHRONIC NON-A, NON-B HEPATITIS - DETECTION BY THE POLYMERASE CHAIN-REACTION USING MULTIPLE PRIMER SETS SO ARCHIVES OF VIROLOGY LA English DT Article ID VIRUS; GENOME AB The recently introduced antibody test for hepatitis C virus (HCV) infection has proven to have certain limitations. Since HCV itself is usually present in clinical specimens at very low titers, a useful assay for the virus must have very high sensitivity. We have developed a simple, highly sensitive assay for HCV RNA based on the polymerase chain reaction (PCR). In this test, RNA extracted from HCV infected serum or plasma is used as the template for double PCR with nested primers. Sensitivity studies demonstrate that this assay is able to detect HCV at or beyond the sensitivity level of chimpanzee infectivity. We tested, with several sets of nested primers, 40 patients with chronic non-A, non-B hepatitis (36 seropositive and 4 seronegative) and found that 35/40 were PCR positive including all 4 seronegative patients. Normal human plasma and plasma from hepatitis B infected patients did not react in this test. This assay has proven to be valuable for determining the presence of HCV in various samples; furthermore, it offers the possibility of diagnosis of HCV infection in seronegative patients. C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIROL,HEPATITIS RES LAB,BETHESDA,MD 20014. NIDDK,LIVER DIS SECT,BETHESDA,MD. NR 10 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 1992 SU 4 BP 172 EP 178 PG 7 WC Virology SC Virology GA JK521 UT WOS:A1992JK52100036 ER PT B AU MORALES, TI AF MORALES, TI BE KUETTNER, KE SCHLEYERBACH, R PEYRON, JG HASCALL, VC TI POLYPEPTIDE REGULATORS OF MATRIX HOMEOSTASIS IN ARTICULAR-CARTILAGE SO ARTICULAR CARTILAGE AND OSTEOARTHRITIS LA English DT Proceedings Paper CT INTERNATIONAL WORKSHOP ON ARTICULAR CARTILAGE AND OSTEOARTHRITIS CY MAY 12-16, 1991 CL WIESBADEN, GERMANY SP HOECHST WERK KALLE ALBERT, WHO RP MORALES, TI (reprint author), NIDR,BONE RES BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 31 Z9 31 U1 0 U2 0 PU RAVEN PRESS PI NEW YORK PA NEW YORK BN 0-88167-862-7 PY 1992 BP 265 EP 279 PG 15 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA BV29K UT WOS:A1992BV29K00017 ER PT B AU BAKER, RF AF BAKER, RF BE Geshwiler, M TI CAMPUS INTERNAL ENVIRONMENTAL CONSIDERATIONS FOR HEALTH-CARE AND BIOMEDICAL-RESEARCH FACILITIES SO ASHRAE TRANSACTIONS, 1992, VOL 98, PT 1 SE ASHRAE TRANSACTIONS LA English DT Proceedings Paper CT Technical and Symposium Papers of the 1992 Winter Meeting of the American-Society-of-Heating-Refrigerating-and-Air-Conditioning-Engineers -Incorporated CY JAN 25-29, 1992 CL ANAHEIM, CA SP AMER SOC HEATING REFRIGERATING & AIR CONDITIONING ENGINEERS INC C1 US DEPT HHS,NATL INST HLTH,BETHESDA,MD 20014. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEATING, REFRIGERATING AND AIR-CONDITIONING ENGS PI ATLANTA PA 1791 TULLIE CIRCLE NE, ATLANTA, GA 30329 J9 ASHRAE TRAN PY 1992 VL 98 BP 1062 EP 1064 PN 1 PG 3 WC Construction & Building Technology; Engineering, Mechanical SC Construction & Building Technology; Engineering GA BA61J UT WOS:A1992BA61J00103 ER PT J AU BANWELL, MG PETERS, SC GREENWOOD, RJ MACKAY, MF HAMEL, E LIN, CM AF BANWELL, MG PETERS, SC GREENWOOD, RJ MACKAY, MF HAMEL, E LIN, CM TI SEMISYNTHESES, X-RAY CRYSTAL-STRUCTURES AND TUBULIN-BINDING PROPERTIES OF 7-OXODEACETAMIDOCOLCHICINE AND 7-OXODEACETAMIDOISOCOLCHICINE SO AUSTRALIAN JOURNAL OF CHEMISTRY LA English DT Article ID METHYL-ETHER; B-RING; COLCHICINE; ANALOGS AB Commercially available (-)-colchicine (1) has been converted, via deacetylcolchiceine (4), into a mixture of 7-oxodeacetamidocolchicine (2) and 7-oxodeacetamidoisocolchicine (3). The X-ray structures and tubulin-binding properties of these title ketones are described. C1 LA TROBE UNIV,DEPT CHEM,BUNDOORA,VIC 3083,AUSTRALIA. NCI,DCT,DTP,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RP BANWELL, MG (reprint author), UNIV MELBOURNE,SCH CHEM,PARKVILLE,VIC 3052,AUSTRALIA. RI Banwell, Martin/H-8354-2014 NR 32 TC 14 Z9 16 U1 0 U2 0 PU C S I R O PUBLICATIONS PI COLLINGWOOD PA 150 OXFORD ST, PO BOX 1139, COLLINGWOOD VICTORIA 3066, AUSTRALIA SN 0004-9425 J9 AUST J CHEM JI Aust. J. Chem. PY 1992 VL 45 IS 10 BP 1577 EP 1588 DI 10.1071/CH9921577 PG 12 WC Chemistry, Multidisciplinary SC Chemistry GA JV579 UT WOS:A1992JV57900003 ER PT J AU BANWELL, MG CAMERON, JM CORBETT, M DUPUCHE, JR HAMEL, E LAMBERT, JN LIN, CM MACKAY, MF AF BANWELL, MG CAMERON, JM CORBETT, M DUPUCHE, JR HAMEL, E LAMBERT, JN LIN, CM MACKAY, MF TI SYNTHESIS AND TUBULIN-BINDING PROPERTIES OF SOME AC-RING AND ABC-RING ANALOGS OF ALLOCOLCHICINE SO AUSTRALIAN JOURNAL OF CHEMISTRY LA English DT Article ID COLCHICINE ANALOGS; CRYSTAL-STRUCTURE; ANTITUBULIN ACTIVITY; ARYLBORONIC ACIDS; NATURAL-PRODUCTS; POLYMERIZATION; INHIBITION; MECHANISM AB Fourteen analogues [compounds (8), (9) and (11)-(22)] of the powerful antimitotic agent allocolchicine (5) have been prepared and evaluated for their ability to prevent tubulin polymerization. The X-ray structure of one of the more active compounds, tricycle (20), is reported. C1 LA TROBE UNIV,DEPT CHEM,BUNDOORA,VIC 3083,AUSTRALIA. NCI,DCT,DTP,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RP BANWELL, MG (reprint author), UNIV MELBOURNE,SCH CHEM,PARKVILLE,VIC 3052,AUSTRALIA. RI Banwell, Martin/H-8354-2014 NR 43 TC 25 Z9 26 U1 0 U2 3 PU C S I R O PUBLICATIONS PI COLLINGWOOD PA 150 OXFORD ST, PO BOX 1139, COLLINGWOOD VICTORIA 3066, AUSTRALIA SN 0004-9425 J9 AUST J CHEM JI Aust. J. Chem. PY 1992 VL 45 IS 12 BP 1967 EP 1982 PG 16 WC Chemistry, Multidisciplinary SC Chemistry GA KC169 UT WOS:A1992KC16900004 ER PT J AU FUJINO, Y LI, Q CHUNG, H HIKITA, N NUSSENBLATT, RB GERY, I CHAN, CC AF FUJINO, Y LI, Q CHUNG, H HIKITA, N NUSSENBLATT, RB GERY, I CHAN, CC TI IMMUNOPATHOLOGY OF EXPERIMENTAL AUTOIMMUNE UVEORETINITIS IN PRIMATES SO AUTOIMMUNITY LA English DT Article DE EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; PINEALITIS; PRIMATE; SUBRETINAL FIBROSIS; LYMPHOCYTE-B; OCULAR INFLAMMATION AB The eyes and pineal glands from 10 monkeys immunized with S-antigen were studied using routine histopathological and immunohistochemical techniques. Seven out of 10 animals developed uveitis between 19 and 33 days after the initial immunization. Histopathology of the eyes harvested 70 days after immunization showed moderate to marked uveoretinitis, subretinal fibrosis, retinal necrosis and gliosis. The pineal glands demonstrated chronic pinealitis. The infiltrating cells were both CD3 and CD19/CD22 lymphocytes with a ratio of 1.4 in the eye and 2.2 in the pineal gland. The ratio of CD4 to CD8 lymphocytes was 1.5:1. MHC Class II antigens and adhesion molecule (ICAM-1) were observed on resident cells. The influx of B lymphocytes and the formation of subretinal fibrosis differentiate the disease in the monkey from that in the rat and mouse. These findings are similar to Vogt-Koyanagi-Harada syndrome and subretinal fibrosis with uveitis syndrome in human. C1 NEI,IMMUNOL LAB,BLDG 10,ROOM 10N206,BETHESDA,MD 20892. NR 0 TC 8 Z9 10 U1 0 U2 1 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 0891-6934 J9 AUTOIMMUNITY JI Autoimmunity PY 1992 VL 13 IS 4 BP 303 EP 309 DI 10.3109/08916939209112339 PG 7 WC Immunology SC Immunology GA KA152 UT WOS:A1992KA15200007 PM 1472640 ER PT J AU FINCH, SC LINET, MS AF FINCH, SC LINET, MS TI CHRONIC LEUKEMIAS SO BAILLIERES CLINICAL HAEMATOLOGY LA English DT Review ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOMONOCYTIC LEUKEMIA; CHRONIC GRANULOCYTIC-LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; SINGLE TREATMENT COURSE; HAIRY-CELL LEUKEMIA; PROGNOSTIC FACTORS; CANCER INCIDENCE; FOLLOW-UP C1 NCI, EPIDEMIOL & BIOSTAT PROGRAM, ROCKVILLE, MD 20892 USA. RP FINCH, SC (reprint author), UNIV MED & DENT NEW JERSEY, ROBERT WOOD JOHNSON MED SCH & COOPER HOSP, 1 COOPER PL, CAMDEN, NJ 08103 USA. NR 144 TC 34 Z9 34 U1 1 U2 1 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0950-3536 J9 BAILLIERE CLIN HAEM JI Baillieres Clin. Haematol. PD JAN PY 1992 VL 5 IS 1 BP 27 EP 56 DI 10.1016/S0950-3536(11)80034-X PG 30 WC Hematology SC Hematology GA JJ871 UT WOS:A1992JJ87100003 PM 1350742 ER PT J AU LAKATTA, EG TALO, A CAPOGROSSI, MC SPURGEON, HA STERN, MD AF LAKATTA, EG TALO, A CAPOGROSSI, MC SPURGEON, HA STERN, MD TI SPONTANEOUS SARCOPLASMIC-RETICULUM CA-2+ RELEASE LEADS TO HETEROGENEITY OF CONTRACTILE AND ELECTRICAL-PROPERTIES OF THE HEART SO BASIC RESEARCH IN CARDIOLOGY LA English DT Article DE CARDIAC CELLS; SARCOPLASMIC RETICULUM; SPONTANEOUS CA-2+ OSCILLATIONS; ARRHYTHMIAS ID CARDIAC PURKINJE-FIBERS; TRANSIENT INWARD CURRENT; INTRACELLULAR CALCIUM; VENTRICULAR MYOCYTES; RAT-HEART; MECHANICAL OSCILLATIONS; LIGHT FLUCTUATION; MAMMALIAN HEART; MUSCLE; RYANODINE AB The cytosolic Ca2+ (Ca(i)) oscillation generated by the sarcoplasmic reticulum (SR) in response to an action potential (AP) occurs relatively synchronously within and among cells. The SR can also generate spontaneous Ca(i) oscillations (S-CaOs), i.e., not triggered by sarcolemmal depolarization. The local increase in Ca(i) due to S-CaOs is equivalent to that induced by an AP. Heterogeneity of diastolic Ca(i) caused by asynchronous S-CaOs among cells within myocardial tissue leads to heterogeneous myofilament activation, the summation of which produces a Ca2+-dependent component to diastolic tone. The local increases in Ca(i) due to S-CaOs also cause oscillatory sarcolemmal depolarizations due to Ca2+ modulation of the Na/Ca exchanger and of non-specific cation channels. Thus, inhomogeneous levels of diastolic Ca(i) may lead to heterogeneity in cell coupling and thus may also affect the impulse conduction. The magnitude of the S-CaOs induced diastolic tonus and membrane depolarization varies with the extent to which S-CaOs are synchronized; partially synchronized S-CaOs following an AP induced SR Ca2+ release produce an aftercontraction and after depolarization. When local S-CaOs is sufficiently synchronized within the cell the resultant depolarization summates and can be sufficient to trigger spontaneous AP. Inhomogeneity of diastolic SR Ca2+ loading and sarcomere lengths within individual cardiac cells due to S-CaOs leads to inhomogeneous systolic Ca(i) levels and sarcomere length inhomogeneities in response a subsequent AP; this heterogeneity compromises the systolic contraction amplitude. Heterogeneity of systolic Ca(i) among cells due to diastolic S-CaOs also leads to heterogeneity of AP repolarization times, due, to heterogeneous Ca(i) modulation of the Na/Ca exchanger, the non-specific cation channel and of the L type sarcolemmal Ca2+ channel. S-CaOs occurrence during a long AP plateau may also modulate the removal of voltage inactivation of L type Ca2+ channels and affect the likelihood of the occurrence of ''early after depolarizations.'' Thus, as a single entity, S-CaOs may be implicated in diverse manifestations of heart failure - impaired systolic performance, increased diastolic tonus and an increased probability for the occurrence of arrhythmias. RP LAKATTA, EG (reprint author), NIA,CARDIOVASC SCI LAB,GERONTOL RECH INST,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 63 TC 18 Z9 18 U1 0 U2 2 PU DR DIETRICH STEINKOPFF VERLAG PI BERLIN 33 PA C/O SPRINGER-VERLAG, HEIDELBERGER PLATZ 3, 1000 BERLIN 33, GERMANY SN 0300-8428 J9 BASIC RES CARDIOL JI Basic Res. Cardiol. PY 1992 VL 87 SU 2 BP 93 EP 104 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA KQ212 UT WOS:A1992KQ21200010 PM 1299213 ER PT B AU WANG, YH DHARIWAL, KR LEVINE, M AF WANG, YH DHARIWAL, KR LEVINE, M BE SAUBERLICH, HE MACHLIN, LJ TI ASCORBIC-ACID BIOAVAILABILITY IN HUMANS - ASCORBIC-ACID IN PLASMA, SERUM, AND URINE SO BEYOND DEFICIENCY: NEW VIEWS ON THE FUNCTION AND HEALTH EFFECTS OF VITAMINS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Proceedings Paper CT CONF ON BEYOND DEFICIENCY : NEW VIEWS ON THE FUNCTION AND HEALTH EFFECTS OF VITAMINS CY FEB 09-12, 1992 CL ARLINGTON, VA SP NEW YORK ACAD SCI, HOFFMANN LA ROCHE, BASF FINE CHEM, EISAI, GEN NUTR PROD, HENKEL, MEAD JOHNSON NUTR GRP, TAKEDA CHEM IND, TAKEDA USA RP WANG, YH (reprint author), NIDDKD,CELL BIOL & GENET LAB,BLDG 8,ROOM 415,BETHESDA,MD 20892, USA. NR 0 TC 14 Z9 14 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA NEW YORK BN 0-89766-750-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1992 VL 669 BP 383 EP 386 PG 4 WC Public, Environmental & Occupational Health; Nutrition & Dietetics SC Public, Environmental & Occupational Health; Nutrition & Dietetics GA BX01N UT WOS:A1992BX01N00047 ER PT B AU MCELVANEY, NG BIRRER, P CHANGSTROMAN, LM CRYSTAL, RG AF MCELVANEY, NG BIRRER, P CHANGSTROMAN, LM CRYSTAL, RG BE Grassi, C Travis, J Casali, L Luisetti, M TI NEUTROPHILS, NEUTROPHIL ELASTASE AND THE FRAGILE LUNG - THE PATHOGENESIS AND THERAPEUTIC STRATEGIES RELATING TO LUNG DERANGEMENT IN THE COMMON HEREDITARY LUNG DISORDERS SO BIOCHEMISTRY OF PULMONARY EMPHYSEMA SE CURRENT TOPICS IN REHABILITATION LA English DT Proceedings Paper CT Workshop on Update in Biochemistry of Pulmonary Emphysema CY SEP 07, 1990 CL PAVIA, ITALY SP UNIV STUDI PAVIA, IST RICOVERO & CURA CARATTERE SCI, POLICLIN SAN MATTEO, FDN RHONE POULENC RORER SCI MEDICHE, FDN S MAUGERI C1 NHLBI,PULM BRANCH,BETHESDA,MD 20892. RI McElvaney, Noel/A-6809-2010 NR 0 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER-VERLAG, LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL RD FARNCOMBE, GODALMING, SURREY, ENGLAND GU7 1NH BN 3-540-19775-3 J9 CURR T REH PY 1992 BP 169 EP 187 PG 19 WC Biochemistry & Molecular Biology; Respiratory System SC Biochemistry & Molecular Biology; Respiratory System GA BA33Y UT WOS:A1992BA33Y00013 ER PT J AU KREITMAN, RJ CHAUDHARY, VK SIEGALL, CB FITZGERALD, DJ PASTAN, I AF KREITMAN, RJ CHAUDHARY, VK SIEGALL, CB FITZGERALD, DJ PASTAN, I TI RATIONAL DESIGN OF A CHIMERIC TOXIN - AN INTRAMOLECULAR LOCATION FOR THE INSERTION OF TRANSFORMING GROWTH-FACTOR ALPHA WITHIN PSEUDOMONAS EXOTOXIN AS A TARGETING LIGAND SO BIOCONJUGATE CHEMISTRY LA English DT Article ID RECOMBINANT FUSION PROTEIN; FACTOR RECEPTOR; ESCHERICHIA-COLI; TUMOR-CELLS; DOMAIN-II; EXPRESSION; INTERLEUKIN-6; CYTOTOXICITY; IMMUNOTOXIN; TOXICITY AB To investigate the potential utility of Pseudomonas exotoxin (PE) in forming rationally designed chemotherapeutic agents, we inserted a cDNA encoding transforming growth factor-alpha (TGF-alpha) at several locations in a gene encoding a mutant full-length PE (PE4E) which does not bind to the PE receptor. After expression in Escherichia coli, we purified the chimeric toxins to near homogeneity and showed that they were specifically cytotoxic to human epidermoid, ovarian, colon, and hepatocellular carcinoma lines. Like the previously reported TGF-alpha-PE40 (11), one of the new molecules (TGF-alpha-PE4E) contains the ligand at the amino terminus. Two additional chimeras (PE4E-TGF-alpha and PE4E-TGF-alpha-598-613) each contain TGF-alpha inserted near the carboxyl terminus of PE. We show that preservation of the correct PE carboxyl-terminal amino acid sequence, REDLK, allows the toxins containing TGF-alpha carboxyl inserts to retain significant cytotoxicity against target cells, since another molecule (PE4E-TGF-alpha-ILK) containing a nonfunctional carboxyl-terminal sequence was over 100-fold less active. The chimeric toxins with TGF-alpha had the same binding affinity for the EGF receptor whether the ligand occupied the amino or carboxyl position. Molecules with TGF-alpha near the carboxyl position were consistently less active against target cells but also less toxic to mice than those with TGF-alpha at the amino terminus, indicating both types of molecules might be therapeutically effective. Our results establish that a ligand can be placed near the carboxyl terminus of PE, within the portion of the toxin that translocates to the cytosol. The amino-terminal position in such molecules is then available for the placement of other targeting ligands. RP PASTAN, I (reprint author), NCI,DIV CANC BIOL,MOLEC BIOL LAB,9000 ROCKVILLE PIKE,37-4E16,BETHESDA,MD 20892, USA. NR 31 TC 26 Z9 26 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JAN-FEB PY 1992 VL 3 IS 1 BP 58 EP 62 DI 10.1021/bc00013a009 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA HD182 UT WOS:A1992HD18200009 PM 1616950 ER PT J AU KREITMAN, RJ SIEGALL, CB CHAUDHARY, VK FITZGERALD, DJ PASTAN, I AF KREITMAN, RJ SIEGALL, CB CHAUDHARY, VK FITZGERALD, DJ PASTAN, I TI PROPERTIES OF CHIMERIC TOXINS WITH 2 RECOGNITION DOMAINS - INTERLEUKIN 6 AND TRANSFORMING GROWTH-FACTOR ALPHA AT DIFFERENT LOCATIONS IN PSEUDOMONAS EXOTOXIN SO BIOCONJUGATE CHEMISTRY LA English DT Article ID FUSION PROTEIN; TUMOR-CELLS; FACTOR-I; RECEPTORS; CANCER; CYTOTOXICITY; EXPRESSION; CARCINOMA; IL6-PE40; TOXICITY AB Pseudomonas exotoxin (PE) is a potent cytotoxic agent that is composed of 613 amino acids arranged into three major domains. We have previously identified two positions where ligands can successfully be placed in PE to direct it to cells with specific surface receptors. One site is at the amino terminus and the other is close to but not at the C-terminus. To examine the possibility of constructing oncotoxins with two different recognition elements that will bind to two different receptors, we have placed cDNAs encoding either transforming growth factor-alpha (TGF-alpha) or interleukin 6 (IL6) at the 5' end of a PE gene and also inserted a cDNA encoding TGF-alpha near the 3' end of the PE gene. The plasmids encoding these chimeric toxins were expressed in Escherichia coli and the chimeric proteins purified to near homogeneity. In all the new toxins, the TGF-alpha near the C-terminus was inserted after amino acid 607 of PE and followed by amino acids 604-613 so that the correct PE C-terminus (REDLK) was preserved. For each chimera, the toxin portion was either PE4E, in which the cell binding domain (domain Ia) is mutated, PE40, in which domain la is deleted, or PE38, in which domain la and part of domain Ib are deleted. These derivatives of PE do not bind to the PE receptor and allow 607, 355, or 339 amino acids, respectively, between the two ligands. Chimeric toxins containing two TGF-alpha ligands were all cytotoxic to human cancer cells expressing EGF receptors, while those containing one IL6 and one TGF-alpha ligand were cytotoxic toward cells expressing either IL6 or EGF receptors, or both. The effect of distance separating the two ligands was evaluated using cytotoxicity assays and [I-125]EGF displacement assays. The animal toxicity of two of the bifunctional chimeric toxins was investigated in mice. Our results establish that two ligands can be placed in different locations within PE simultaneously and that adding IL6 to the amino terminus of PE which already contains TGF-alpha near the carboxyl terminus decreases animal toxicity in vivo and yet increases cytotoxicity against some cell lines in vitro. RP PASTAN, I (reprint author), NCI,DCBDC,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 22 TC 16 Z9 16 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JAN-FEB PY 1992 VL 3 IS 1 BP 63 EP 68 DI 10.1021/bc00013a010 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA HD182 UT WOS:A1992HD18200010 PM 1616951 ER PT J AU ADAMO, M ROBERTS, CT LEROITH, D AF ADAMO, M ROBERTS, CT LEROITH, D TI HOW DISTINCT ARE THE INSULIN AND INSULIN-LIKE GROWTH FACTOR-I SIGNALING SYSTEMS SO BIOFACTORS LA English DT Review DE INSULIN; INSULIN-LIKE GROWTH FACTOR-I; SIGNALING SYSTEMS ID HUMAN-SKIN FIBROBLASTS; IGF BINDING-PROTEIN; MESSENGER RIBONUCLEIC-ACID; COOH-TERMINAL TRUNCATION; MONOCLONAL-ANTIBODY; ENDOTHELIAL-CELLS; FACTOR RECEPTOR; AMNIOTIC-FLUID; DNA-SYNTHESIS; RAT-HEART AB Insulin and insulin-like growth factor I (IGF-I) are closely related peptides. Insulin is primarily involved in regulating carbohydrate, fat and protein metabolism. IGF-I, however, regulates growth and development of the whole organism as well as differentiated functions in specific tissues. Each of these functions are mediated by specific tyrosine kinase receptors expressed on the cell surface. The insulin and IGF-I receptors, though separate gene products, are very similar. Amino acid similarities range between 40 and 85% in different domains, the highest degree of homology being found in the tyrosine kinase domain. Tertiary structure similarities further explain the interactions of each ligand with the heterologous receptor; thus insulin receptors bind insulin with high affinity and IGF-I with lower affinity, and the opposite is true for the IGF-I receptor. Since each ligand can stimulate both receptors and both receptors seem capable of mediating both metabolic and growth activities, what separates these two distinct physiological roles? The interaction of the ligands with their own specific high affinity receptors is facilitated by the presence of IGF-specific binding proteins (BPs) which, however, do not bind insulin. These BPs, found both in the circulation and in tissues, bind all the circulating IGFs and transport the IGFs to their target tissues, thus ensuring that at physiological concentrations IGF-I will only interact with its own receptor. Furthermore, they modulate IGF effects. Since insulin circulates at much lower concentrations compared with the IGFs, this ensures that insulin will only interact with high-affinity insulin receptors. In addition to the specificity at the level of ligand binding it seems that each receptor has different inherent biological properties. Thus, the IGF-I receptor is inherently more mitogenic and the insulin receptor more of a metabolically active receptor. The presence of hybrid receptors (i.e. insulin receptor alpha-beta-subunits and IGF-I receptor alpha-beta-subunits) making up the tetramer in certain tissues has added a new dimension to our understanding of the functional roles of these receptors. These hybrid receptors may help explain how IGF-I may mediate metabolic effects and how insulin may mediate growth activity in certain cells. These seemingly unphysiological effects may be mediated by these hybrids in cell types in which these effects have been noted. Further elucidation of the structure-function relationships of this family of peptides and receptors as well as their endogenous substrates and complete signal transduction pathways will bring about many new answers and help distinguish these distinct pathways. C1 NIH,DIABET BRANCH,BETHESDA,MD 20892. NR 51 TC 47 Z9 47 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0951-6433 J9 BIOFACTORS JI Biofactors PD JAN PY 1992 VL 3 IS 3 BP 151 EP 157 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA HA918 UT WOS:A1992HA91800001 PM 1599609 ER PT J AU ALAYASH, AI FRANTANTONI, JC AF ALAYASH, AI FRANTANTONI, JC TI EFFECTS OF HYPOTHERMIC CONDITIONS ON THE OXYGEN CARRYING-CAPACITY OF CROSS-LINKED HEMOGLOBINS SO BIOMATERIALS ARTIFICIAL CELLS AND IMMOBILIZATION BIOTECHNOLOGY LA English DT Article ID SUBSTITUTE AB In view of the potential application for hemoglobin-based oxygen carriers (HBOCs) in organ perfusion under hypothermic conditions, we examined the temperature dependence of oxygen equilibrium curves (OECs) at 15-37-degrees-C of three HBOCs: HbA-FMDA and HbBv-FMDA, produced by the reaction of human or bovine oxyHb with fumaryl mono-dibromoaspirin, and HbA-DBBF, produced by the reaction of human deoxyHb with bis(3,5-dibromosalicyl) fumarate. OECs for HbA-DBBF, HbA-FMDA and HbBv-FMDA at 37-degrees-C were right shifted (P50 = 24.5, 17 and 35 torr, respectively). van't Hoff's rule gave the following values for the heat of oxygenation (DELTA-H in Kcal/mol): HbA-DBBF (-12.2 +/- 2.8), HbA-FMDA (-12.0 +/- 2.0), HbBv-FMDA (-10.5 +/- 1.8); these values do not significantly differ from that for native HbA. (-11.5 +/- 2.4). Among the hemoglobins included in this study, HbBv-FMDA had the most favorable oxygenation characteristics at low temperatures (a P50 of 6.0 torr at 15-degrees-C as compared to only 2-3 torr for the other hemoglobins in the study). Recently, however, a human hemoglobin crosslinked with bispyridoxyl tetraphosphate was reported to have a P50 of 15 torr at 16-degrees-C (Keipert et al, Transfusion 1989; 29: 768-773). Therefore, precise knowledge of the oxygen delivering capacity of any potential HBOC should be explored under hypothermic conditions as performance under these conditions may determine its usefulness as an organ perfusate. RP ALAYASH, AI (reprint author), NIH,FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892, USA. NR 5 TC 3 Z9 3 U1 0 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 1055-7172 J9 BIOMAT ARTIF CELL IM JI Biomater. Artif. Cells Immobil. Biotechnol. PY 1992 VL 20 IS 2-4 BP 259 EP 262 PG 4 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA JM745 UT WOS:A1992JM74500008 PM 1391440 ER PT J AU WASCHEK, JA KRAJNIAK, KG BRAVO, DT AGOSTON, DV AF WASCHEK, JA KRAJNIAK, KG BRAVO, DT AGOSTON, DV TI REGULATION OF THE HUMAN AND MOUSE VASOACTIVE-INTESTINAL-PEPTIDE (VIP) GENES SO BIOMEDICAL RESEARCH-TOKYO LA English DT Article ID RAT SUPRACHIASMATIC NUCLEUS; MESSENGER-RNA; CELLS; EXPRESSION; SEQUENCE AB The expression of the human vasoactive intestinal peptide (VIP) gene was examined in human neuroblastoma cell lines and in transgenic mice. Transfection studies in human neuroblastoma cell lines indicated that multiple regulatory elements span the 5' flanking sequence of the VIP gene, and that cell-specific transcriptional effects are mediated by sequences as far as 4.0 to 4.6 kilobases (kb) upstream from the VIP gene transcription start site. Regulatory sequences that conferred a high level of VIP expression and phorbol ester induction were localized to a 650 basepair (bp) fragment that contained three 9-bp sequences repeated 65 bp downstream on the same fragment. These and other sequences on the fragment had no obvious homology to consensus regulatory elements that bind known transcription factors. The significance of these and other human VIP gene regulatory sequences was examined in a transgenic mouse model. A chimeric gene containing 5.2 kb VIP gene 5' flanking sequences fused to a reporter gene resulted in expression of the reporter in the intestine but not in CNS sites of VIP expression. The data suggest that the gene construction contains sequences that target expression to the intestine and perhaps other neural crest-derived sites, but that expression in the CNS requires enhancer sequences located elsewhere on the gene, or that the human gene fuctions inefficiently in the mouse CNS. For future studies we have isolated mouse VIP genomic clones and have begun to characterize the gene in the mouse. C1 NICHHD, DEV NEUROBIOL LAB, BETHESDA, MD 20892 USA. RP UNIV CALIF LOS ANGELES, LOS ANGELES, CA 90024 USA. NR 21 TC 7 Z9 7 U1 0 U2 0 PU BIOMEDICAL RESEARCH PRESS LTD PI SAPPORO PA HOKKAIDO UNIV, LAB HISTOLOGY & CYTOLOGY, C/O TOSHIHIKO IWANAGA, KITA 15-NISHI 7, SAPPORO, 060-8638, JAPAN SN 0388-6107 EI 1880-313X J9 BIOMED RES-TOKYO JI Biomed. Res. PY 1992 VL 13 SU 2 BP 1 EP 6 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA KQ830 UT WOS:A1992KQ83000002 ER PT J AU MOODY, TW ZIA, F GOLDSTEIN, AL NAYLOR, PH SARIN, E BRENNEMAN, D KOROS, AMC REUBI, JC KORMAN, LY FRIDKIN, M GOZES, I AF MOODY, TW ZIA, F GOLDSTEIN, AL NAYLOR, PH SARIN, E BRENNEMAN, D KOROS, AMC REUBI, JC KORMAN, LY FRIDKIN, M GOZES, I TI VIP ANALOGS INHIBIT SMALL-CELL LUNG-CANCER GROWTH SO BIOMEDICAL RESEARCH-TOKYO LA English DT Article; Proceedings Paper CT 5TH INTERNATIONAL SYMP ON VIP ( VASOACTIVE INTESTINAL PEPTIDE ) AND RELATED PEPTIDES CY NOV 12-15, 1991 CL SHIZUOKA, JAPAN SP JAPAN FEDERAT ECON ORG, OSAKA PHARM MANUFACTURERS ASSOC, PHARM MANUFACTURERS ASSOC TOKYO, BANYU PHARM, DAICEL CHEM IND, DAIICHI RADIO ISOTOPE LABS, DAINABOT, EARTH CHEM, EIWEISS CHEM, ICI PHARMA ID VASOACTIVE-INTESTINAL-PEPTIDE; HIGH-AFFINITY BINDING; RECEPTORS; SECRETIN; LINES; RAT; POLYPEPTIDE; CARCINOMA; THYMOSIN-ALPHA-1; BRONCHODILATOR AB The ability of VIP analogues to interact with small cell lung cancer (SCLC) cells was investigated. Specific I-125-VIP binding to SCLC cell line NCI-H209 was inhibited with high affinity by VIP, PACAP, VIPhybrid (VIPhyb) and thymosin alpha1 (THNalpha1) (IC50 = 10, 20, 700 and 10000 nM respectively) but not thymosin beta4. I-125-I-VIP bound specifically to 3 out of 5 SCLC biopsy specimens. VIP but not VIPhyb or THNalpha1 elevated the cAMP levels 4-fold using cell lines NCI-H345 and H209. Also, VIPhyb and THNalpha1 inhibited SCLC growth using a clonagenic assay. These data suggest that VIPhyb and THNalpha1 interact with SCLC cells and inhibit proliferation. C1 NICHHD,NEUROCHEM UNIT,LDN,BETHESDA,MD 20892. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT INFECT DIS & MICROBIOL,PITTSBURGH,PA 15261. SANDOZ RES INST,CH-3001 BERN,SWITZERLAND. VET ADM MED CTR,GASTROENTEROL SECT,WASHINGTON,DC 20422. WEIZMANN INST SCI,DEPT ORGAN CHEM,IL-76100 REHOVOT,ISRAEL. SACKLER SCH MED,DEPT CHEM PATHOL,TEL AVIV,ISRAEL. RP MOODY, TW (reprint author), GEORGE WASHINGTON UNIV,SCH MED,DEPT BIOCHEM & MOLEC BIOL,WASHINGTON,DC 20037, USA. NR 29 TC 22 Z9 22 U1 0 U2 0 PU BIOMED RES FOUND PI TOKYO PA KANDA PO BOX 182 CHIYODAKU, TOKYO 101-91, JAPAN SN 0388-6107 J9 BIOMED RES-TOKYO JI Biomed. Res. PY 1992 VL 13 SU 2 BP 131 EP 135 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA KQ830 UT WOS:A1992KQ83000023 ER PT J AU HEBEL, D FURLANO, DC PHILLIPS, RS KOUSHIK, S CREVELING, CR KIRK, KL AF HEBEL, D FURLANO, DC PHILLIPS, RS KOUSHIK, S CREVELING, CR KIRK, KL TI AN ENZYMATIC-SYNTHESIS OF 2-AZIDO-L-TYROSINE SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID TYROSINE PHENOL-LYASE AB Tyrosine-phenol lyase-catalyzed coupling of 3-azidophenol and pyruvic acid produced 2-azido-L-tyrosine in good yield. Preliminary results indicate that this new analogue may serve as a replacement for tyrosine in several enzymatic processes. C1 NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. UNIV GEORGIA,DEPT CHEM,ATHENS,GA 30602. OI Phillips, Robert/0000-0001-8710-562X NR 5 TC 9 Z9 9 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PY 1992 VL 2 IS 1 BP 41 EP 44 DI 10.1016/S0960-894X(00)80651-4 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA HC774 UT WOS:A1992HC77400008 ER PT J AU POZSGAY, V GLAUDEMANS, CPJ ROBBINS, JB SCHNEERSON, R AF POZSGAY, V GLAUDEMANS, CPJ ROBBINS, JB SCHNEERSON, R TI A SYNTHETIC OCTASACCHARIDE MIMICS THE NATIVE, O-SPECIFIC DETERMINANT OF THE SHIGELLA-DYSENTERIAE TYPE-1 LIPOPOLYSACCHARIDE SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID B STREPTOCOCCAL POLYSACCHARIDES; STEREOSELECTIVE SYNTHESIS; CAPSULAR POLYSACCHARIDE; OLIGOSACCHARIDES; ANTIGENS; GLYCOSIDES; FRAGMENTS; CHAIN AB The chemical synthesis of a linear octasaccharide, composed of two contiguous repeating units of the O-specific determinant of Shigella dysenteriae type 1 is described. H-1-NMR data indicate that this octasaccharide possesses conformational features of the native polysaccharide. C1 NIDDK,BETHESDA,MD 20892. NICHHD,BETHESDA,MD 20892. NR 30 TC 15 Z9 15 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PY 1992 VL 2 IS 3 BP 255 EP 260 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA HJ105 UT WOS:A1992HJ10500010 ER PT J AU MINTON, AP AF MINTON, AP TI SIMULATION OF THE TIME COURSE OF MACROMOLECULAR SEPARATIONS IN AN ULTRACENTRIFUGE .1. FORMATION OF A CESIUM-CHLORIDE DENSITY GRADIENT AT 25-DEGREES-C SO BIOPHYSICAL CHEMISTRY LA English DT Article DE MACROMOLECULAR SEPARATIONS BY ULTRACENTRIFUGATION; DENSITY GRADIENT FORMATION; THERMODYNAMIC PROPERTIES OF CSCL SOLUTIONS; HYDRODYNAMIC PROPERTIES OF CSCL SOLUTIONS; CONTROLLED SEDIMENTATION; SEDIMENTATION SIMULATION; CENTRIFUGE RUN OPTIMIZATION AB A method is described for rapid numerical simulation of the time course of the formation of a density gradient of CsCl in an ultracentrifuge at 25-degrees-C. Results of simulations compare well with those of experiments carried out in analytical and preparative ultracentrifuges. RP MINTON, AP (reprint author), NAT INST DIABET DIGEST & KIDNEY DIS,BIOCHEM PHARMACOL LAB,BETHESDA,MD 20892, USA. NR 10 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PD JAN PY 1992 VL 42 IS 1 BP 13 EP 21 DI 10.1016/0301-4622(92)80003-N PG 9 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA HB222 UT WOS:A1992HB22200003 PM 1581511 ER PT J AU RAU, DC PARSEGIAN, VA AF RAU, DC PARSEGIAN, VA TI DIRECT MEASUREMENT OF THE INTERMOLECULAR FORCES BETWEEN COUNTERION-CONDENSED DNA DOUBLE HELICES - EVIDENCE FOR LONG-RANGE ATTRACTIVE HYDRATION FORCES SO BIOPHYSICAL JOURNAL LA English DT Article ID X-RAY-DIFFRACTION; PHOSPHOLIPID-BILAYERS; LIGHT-SCATTERING; POLYAMINES; BINDING; NUCLEOPROTAMINE; COMPLEXES; HEXAMMINE; PROTEIN; STRESS AB Rather than acting by modifying van der Waals or electrostatic double layer interactions or by directly bridging neighboring molecules, polyvalent ligands bound to DNA double helices appear to act by reconfiguring the water between macromolecular surfaces to create attractive long range hydration forces. We have reached this conclusion by directly measuring the repulsive forces between parallel B-form DNA double helices pushed together from the separations at which they have self organized into hexagonal arrays of parallel rods. For all of the wide variety of "condensing agents" from divalent Mn to polymeric protamines, the resulting intermolecular force varies exponentially with a decay rate of 1.4-1.5 angstrom, exactly one-half that seen previously for hydration repulsion. Such behavior qualitatively contradicts the predictions of all electrostatic double layer and van der Waals force potentials previously suggested. It fits remarkably well with the idea, developed and tested here, that multivalent counterion adsorption reorganizes the water at discrete sites complementary to unadsorbed sites on the apposing surface. The measured strength and range of these attractive forces together with their apparent specificity suggest the presence of a previously unexpected force in molecular organization. C1 NIH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20892. RP RAU, DC (reprint author), NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892, USA. NR 40 TC 335 Z9 337 U1 4 U2 47 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 1992 VL 61 IS 1 BP 246 EP 259 PG 14 WC Biophysics SC Biophysics GA HA811 UT WOS:A1992HA81100022 PM 1540693 ER PT J AU RAU, DC PARSEGIAN, VA AF RAU, DC PARSEGIAN, VA TI DIRECT MEASUREMENT OF TEMPERATURE-DEPENDENT SOLVATION FORCES BETWEEN DNA DOUBLE HELICES SO BIOPHYSICAL JOURNAL LA English DT Article ID HYDRATION FORCES; PHOSPHOLIPID-BILAYERS; WATER; IONS AB The assembly of double stranded DNA helices with divalent manganese ion is favored by increasing temperature. Direct force measurements, obtained from the osmotic stress technique coupled with x-ray diffraction, show that the force characteristics of spontaneously precipitated Mn2+-DNA closely resemble those observed previously by us for other counterion condensed DNA assemblies. At temperatures below the critical one for spontaneous assembly, we have quantitated the changes in entropy and manganese ion binding associated with the transition from repulsive to attractive interactions between helices mediated by osmotic stress. The release of structured water surrounding the DNA helix to the bulk solution is the most probable source of increased entropy after assembly. Increasing the water entropy of the bulk solution by changing the manganese salt anion from Cl-to ClO4- predictably and quantitatively increases the transition entropy. This is further evidence for the dominating role of water in the close interaction of polar surfaces. C1 NIH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20892. RP RAU, DC (reprint author), NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892, USA. NR 32 TC 192 Z9 192 U1 1 U2 12 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 1992 VL 61 IS 1 BP 260 EP 271 PG 12 WC Biophysics SC Biophysics GA HA811 UT WOS:A1992HA81100023 PM 1540694 ER PT J AU BAILEY, JJ FLETCHER, JE CHUCK, ET SHRAGER, RI AF BAILEY, JJ FLETCHER, JE CHUCK, ET SHRAGER, RI TI A KINETIC-MODEL OF CD4+ LYMPHOCYTES WITH THE HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) SO BIOSYSTEMS LA English DT Article DE MATHEMATICAL MODELING; CELLULAR KINETICS; LYMPHOCYTES-T; HUMAN IMMUNODEFICIENCY VIRUS ID IMMUNE-DEFICIENCY SYNDROME; HOMOSEXUAL MEN; SELECTIVE LOSS; T-CELLS; INFECTION; INDIVIDUALS; RESPONSES; SYMPTOMS; AIDS AB This report describes a kinetic model of in vitro cytopathology involving interactions of human immunodeficiency virus (HIV) with CD4+ helper T lymphocytes. The model uses nonlinearly coupled, ordinary differential equations to simulate the dynamics of infected and uninfected cells and free virions. It is assumed that resting cells are more readily infected than activated cells, but once infected, only activated cells produce more virus. Resting cells can be activated by some appropriate stimulus (e.g. phytohemagglutinin, soluble antigen). The model predicts that the initial inoculum of virus is taken up by resting cells and without stimulation the system comes to a steady state of two populations, namely infected and uninfected cells. Stimulation of this system produces two additional populations, namely infected and uninfected activated cells which, along with the previous populations, exhibit cyclic behavior of growth, viral expression/release, and death. Additional stimuli enhance or diminish the cyclic behavior depending upon their occurrence in time. These simulations suggest a similar dynamics in human HIV infection and may explain a major factor responsible for the widely varying depletion rate of (CD4+) helper T cells in AIDS patients. RP BAILEY, JJ (reprint author), NIH,DIV COMP RES & TECHNOL,APPLIED STUDIES LAB,BLDG 12A,ROOM 2041,BETHESDA,MD 20892, USA. NR 14 TC 5 Z9 6 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-2647 J9 BIOSYSTEMS JI Biosystems PY 1992 VL 26 IS 3 BP 177 EP 183 DI 10.1016/0303-2647(92)90077-C PG 7 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA HK735 UT WOS:A1992HK73500006 PM 1348962 ER PT J AU JAIN, R GOMER, RH MURTAGH, JJ AF JAIN, R GOMER, RH MURTAGH, JJ TI INCREASING SPECIFICITY FROM THE PCR-RACE TECHNIQUE SO BIOTECHNIQUES LA English DT Article C1 RICE UNIV,HOWARD HUGHES MED INST,HOUSTON,TX 77251. RICE UNIV,DEPT BIOCHEM & CELL BIOL,HOUSTON,TX 77251. NIH,CELLULAR METAB LAB,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM 42604] NR 2 TC 35 Z9 35 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 JAN PY 1992 VL 12 IS 1 BP 58 EP 59 PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GZ184 UT WOS:A1992GZ18400010 PM 1370903 ER PT J AU SHIMOMURA, S KOMATSU, N FRICKHOFEN, N ANDERSON, S KAJIGAYA, S YOUNG, NS AF SHIMOMURA, S KOMATSU, N FRICKHOFEN, N ANDERSON, S KAJIGAYA, S YOUNG, NS TI 1ST CONTINUOUS PROPAGATION OF B19-PAROVIRUS IN A CELL-LINE SO BLOOD LA English DT Article ID B19 HUMAN PARVOVIRUS; HUMAN-BONE MARROW; INVITRO; VIRUS; REPLICATION; INFECTION; CULTURES; PROTEINS C1 JICHI MED SCH,DEPT MED,DIV HEMATOL,MINAMI KAWACHI,TOCHIGI 32904,JAPAN. RP SHIMOMURA, S (reprint author), NHLBI,CLIN HEMATOL BRANCH,CELL BIOL SECT,BLDG 10,ROOM 7C103,BETHESDA,MD 20892, USA. NR 26 TC 81 Z9 85 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 1992 VL 79 IS 1 BP 18 EP 24 PG 7 WC Hematology SC Hematology GA GX614 UT WOS:A1992GX61400002 PM 1728307 ER PT J AU CLEMENS, JM TASKAR, S CHAU, K VALLARI, D SHIH, JWK ALTER, HJ SCHLEICHER, JB MIMMS, LT AF CLEMENS, JM TASKAR, S CHAU, K VALLARI, D SHIH, JWK ALTER, HJ SCHLEICHER, JB MIMMS, LT TI IGM ANTIBODY-RESPONSE IN ACUTE HEPATITIS-C VIRAL-INFECTION SO BLOOD LA English DT Article ID NON-B-HEPATITIS; NON-A; VIRUS C1 ABBOTT LABS,HEPATITIS RES & DEV,N CHICAGO,IL 60064. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,TRANSFUS TRANSMITTED VIRUSES LAB,BETHESDA,MD. NR 11 TC 51 Z9 50 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 1992 VL 79 IS 1 BP 169 EP 172 PG 4 WC Hematology SC Hematology GA GX614 UT WOS:A1992GX61400021 PM 1309424 ER PT J AU PRODOUZ, KN LYTLE, CD BONNER, RF FRATANTONI, JC AF PRODOUZ, KN LYTLE, CD BONNER, RF FRATANTONI, JC TI EFFECTS OF 2 VIRAL INACTIVATION METHODS ON PLATELETS - LASER-UV RADIATION AND MEROCYANINE-540-MEDIATED PHOTOINACTIVATION SO BLOOD CELLS LA English DT Article DE PLATELET; PHOTOINACTIVATION; ULTRAVIOLET RADIATION; MEROCYANINE-540 ID BLOOD PRODUCTS; PROTEINS; MEMBRANE AB Two viral inactivation methods suggested for use with cellular blood products have been evaluated as to their effects on platelets. In the first study, it was proposed that pulsed laser-ultraviolet radiation (UVB) at 308 nm could favor photodamage to UVB-sensitive viral nucleic acid with minimal effects on blood platelets. A "window of efficacy" was observed with UVB doses of 10.5-21.5 J/cm2 at which 4-6 log10 poliovirus were inactivated while platelets were relatively tolerant. However, this "window" occurred only with low-intensity UVB radiation (less-than-or-equal-to 0.25 MW/cm2). Damage to platelet proteins, evident at high laser intensities, was probably due to multiple photon excitation of amino acids. In the second study, platelets and viruses were treated with the photosensitizer, merocyanine 540 (MC 540) (less-than-or-equal-to 24-mu-g/ml), and visible light (450-600 nm) (less-than-or-equal-to 18 J/cm2). Activation of washed platelets by dye/light treatment resulted in a spontaneous release of serotonin, spontaneous aggregation, and marked morphological changes. Increasing concentrations of albumin in the suspension medium protected against dye-mediated photodamage to platelets, but also significantly reduced the antiviral activity of MC 540 and light. These results illustrate the relative sensitivities of platelets and viruses to two inactivation methods and the difficulty in optimizing inactivation of viruses and preservation of platelet function in a protein-rich medium. C1 US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20857. NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RP PRODOUZ, KN (reprint author), NIH,CTR BIOL EVALUAT & RES,BLDG 29,ROOM 329,8800 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Bonner, Robert/C-6783-2015 NR 18 TC 13 Z9 13 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-4684 J9 BLOOD CELLS JI Blood Cells PY 1992 VL 18 IS 1 BP 101 EP 116 PG 16 WC Hematology SC Hematology GA HD602 UT WOS:A1992HD60200008 PM 1617186 ER PT J AU STANTON, BR PARADA, LF AF STANTON, BR PARADA, LF TI THE N-MYC PROTOONCOGENE - DEVELOPMENTAL EXPRESSION AND INVIVO SITE-DIRECTED MUTAGENESIS SO BRAIN PATHOLOGY LA English DT Article ID HUMAN NEURO-BLASTOMA; TERATOCARCINOMA STEM-CELLS; INDUCED MORPHOLOGICAL-DIFFERENTIATION; GERM-LINE TRANSMISSION; ADVANCED DISEASE STAGE; MAJOR LATE PROMOTER; DNA-BINDING DOMAIN; LOOP-HELIX PROTEIN; C-MYC; RETINOIC ACID AB The N-myc proto-oncogene is a member of the superfamily of transcription factors. In mammals, expression of this gene is predominantly restricted to the developing embryo. Specifically, the level of expression is highest in differentiating epithelial components of the embryo including those of the developing brain, kidney and lung. The observation that N-myc is expressed in differentiating but not terminally differentiated structures suggests that these genes may function in the maintenance of cells in a determined or proliferative state. Available evidence suggests that when N-myc expression is down-regulated, cells progress through differentiation and acquire their terminal phenotype. N-myc expression is also correlated with poor prognosis in a number of tumor systems. Since malignant tumors are usually poorly differentiated, this may reflect the role that N-myc plays in preventing differentiation of otherwise determined cells. In vivo site-directed mutagenesis by homologous recombination has made it possible to introduce a variety of mutations into mice. This review summarizes this technology and describes our initial results in the characterization of mice that lack a functional N-myc gene. Specifically, we have observed that in the absence of a functional N-myc gene, embryos arrest in midgestation. This body of work demonstrates that this gene is not required for normal development until the onset of organogenesis. C1 NCI,FREDERICK CANC RES & DEV CTR,MOLEC EMBRYOL SECT,BETHESDA,MD 20892. RI Parada, luis/B-9400-2014 FU NCI NIH HHS [N01-CO-74101] NR 87 TC 33 Z9 34 U1 0 U2 1 PU INT SOC NEUROPATHOLOGY PI ZURICH PA ISN JOURNAL PO BOX, CH-8033 ZURICH, SWITZERLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD JAN PY 1992 VL 2 IS 1 BP 71 EP 83 PG 13 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA HG941 UT WOS:A1992HG94100009 PM 1341949 ER PT J AU CORREA, FMA SAAVEDRA, JM AF CORREA, FMA SAAVEDRA, JM TI CHEMICAL LESION OF THE CIRCUMVENTRICULAR ORGANS WITH MONOSODIUM GLUTAMATE REDUCES THE BLOOD-PRESSURE OF SPONTANEOUSLY HYPERTENSIVE BUT NOT OF ONE-KIDNEY ONE-CLIP HYPERTENSIVE RATS SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH LA English DT Article DE MONOSODIUM GLUTAMATE; ANGIOTENSIN RECEPTOR; ANGIOTENSIN CONVERTING ENZYME; RENAL HYPERTENSIVE RATS; CENTRAL NERVOUS SYSTEM; SPONTANEOUSLY HYPERTENSIVE RATS ID ANGIOTENSIN-CONVERTING ENZYME; II BINDING-SITES; QUANTITATIVE DISTRIBUTION; PITUITARY-GLAND; DISCRETE AREAS; BRAIN; AUTORADIOGRAPHY; FOREBRAIN; SYSTEM AB Subcutaneous injection of monosodium glutamate (MSG) on days 1, 5 and 9 of the experiment (5 g/kg per day) significantly reduced the blood pressure of a group of 10 spontaneously hypertensive rats (SHR) measured 7 and 14 days after treatment (200 +/- 7 mmHg vs 172 +/- 8 mmHg or 185 +/- 3 mmHg, respectively), without affecting that of 11 age-matched Wistar Kyoto (WKY) rats (127 +/- 7 mmHg vs 123 +/- 5 mmHg and 119 +/- 5 mmHg, respectively). Using autoradiographic methods and I-125-Sar1-angiotensin II, receptor binding was shown to be higher in the subfornical organ (SFO) of SHR (332 +/- 31 fmol/mg protein) when compared to WKY rats (240 +/- 30 fmol/mg protein) and similar (222 +/- 21 vs 170 +/- 14 fmol/mg protein) in the paraventricular nucleus (PVN). Binding to angiotensin-converting enzyme (ACE) was evaluated using the ACE inhibitor I-125-35 IA as ligand. Binding to ACE was lower in SHR in the PVN and the globus pallidus (GP) of SHR when compared to WKY rats (PVN: 111 +/- 9 vs 172 +/- 13 and GP: 163 +/- 2 vs 213 +/- 7 fmol/mg protein) and similar in the SFO, choroid plexus (ChP) and caudate nucleus (CD) of both strains (SFO: 779 +/- 107 vs 805 +/- 169; ChP: 2,780 +/- 2 10 vs 3,140 +/- 360 and CD: 461 +/- 42 vs 424 +/- 18 fmol/mg protein). No changes in angiotensin II (Ang II) receptor number or binding to ACE were detected in these brain areas after MSG treatment of SHR or WKY rats. Similar MSG treatment did not affect the development of one kidney-one clip(1K-1C) experimental hypertension in a group of 10 Wistar rats when compared to a group of 8 saline-treated animals. 1K-1C surgery was performed 7 days after MSG treatment and blood pressure measured before (saline 123 +/- 1 mmHg vs MSG 126 +/- 1 mmHg) and both 7 (151 +/- 4 mmHg vs 158 +/- 3 mmHg) and 15 days (163 +/- 4 mmHg vs 172 +/- 6 mmHg) after surgery. The results support the hypothesis of a differential role of central MSG-sensitive mechanisms in genetic and experimental renal forms of hypertension. C1 NIMH,PHARMACOL SECT,BETHESDA,MD 20892. RP CORREA, FMA (reprint author), UNIV SAO PAULO,FAC MED RIBEIRAO PRETO,DEPT FARMACOL,BR-14049 RIBEIRAO PRETO,SP,BRAZIL. RI Correa, Fernando /D-1614-2012 OI Correa, Fernando /0000-0003-4067-9524 NR 16 TC 2 Z9 2 U1 0 U2 0 PU ASSOC BRAS DIVULG CIENTIFICA PI SAO PAULO PA FACULDADE MEDICINA, SALA 21, 14049 RIBEIRAO PRETO, SAO PAULO, BRAZIL SN 0100-879X J9 BRAZ J MED BIOL RES JI Brazilian J. Med. Biol. Res. PY 1992 VL 25 IS 5 BP 515 EP 519 PG 5 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA HY848 UT WOS:A1992HY84800012 PM 1342228 ER PT J AU KRIEGER, EM YAMORI, Y LOVENBERG, WM AF KRIEGER, EM YAMORI, Y LOVENBERG, WM TI ANGIOTENSIN CONVERTING ACTIVITY ASSESSED INVIVO IS INCREASED IN HEREDITARY HYPERTENSIVE RATS SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH LA English DT Article DE CONVERTING ENZYME; ANGIOTENSIN-I; ANGIOTENSIN-II; BRADYKININ; GENETIC HYPERTENSION; SPONTANEOUSLY HYPERTENSIVE RATS (SHR); SPONTANEOUSLY HYPERTENSIVE STROKE-PRONE RATS (SHRSP) ID ONE-KIDNEY; ENZYME; ENDOTHELIUM; BRADYKININ; RESPONSES; ARTERIES; RELEASE; SYSTEM; DRUGS AB 1. The angiotensin converting enzyme (ACE) activity of spontaneously hypertensive (SHR) and spontaneously hypertensive stroke-prone (SHRSP) rats was compared to the ACE activity of normotensive Wistar-Kyoto rats (WKY). 2. ACE activity was assessed indirectly in conscious unrestrained tats using the equipressor response end point to simultaneously calculate the extent of conversion of angiotensin I (AI) to angiotensin II (AII) and the pulmonary degradation of bradykinin (BK). 3. The pulmonary degradation of BK was significantly elevated (99.4%) in SHR rats whereas the elevation was not significant in SHRSP rats (99.2%) compared to WKY rats, even though the pulmonary inactivation of BK in WKY rats was higher (98.6%) than in normotensive Wistar rats (95.6% and 97.5%) previously studied. 4. Blood pressure responsiveness to intra-aortically injected BK (bolus injection and infusion) was markedly increased in SHR and SHRSP rats with no change in reactivity to sodium nitroprusside. 5. Conversion of AI to AII assessed by the equipressor doses of the hormones which produced a 20-mmHg rise in blood pressure was markedly elevated in SHR (86 +/- 4%) and SHRSP (80 +/- 7%) rats when compared to WKY tats (38 +/- 4%). 6. The marked increase in conversion of AI to AII in hypertensive animals, accompanied by an increased pulmonary degradation of BK in SHR rats, suggests that ACE activity is increased in conscious SHR and SHRSP rats and may participate in the genesis of hypertension in this model of genetic hypertension. C1 NHLBI,BIOCHEM PHARMACOL SECT,BETHESDA,MD 20892. RP KRIEGER, EM (reprint author), UNIV SAO PAULO,FAC MED,INST CORACAO,UNIDADE HIPERTENSAO,CAIXA POSTAL 11450,BR-05422-970 SAO PAULO,BRAZIL. NR 25 TC 5 Z9 5 U1 0 U2 0 PU ASSOC BRAS DIVULG CIENTIFICA PI SAO PAULO PA FACULDADE MEDICINA, SALA 21, 14049 RIBEIRAO PRETO, SAO PAULO, BRAZIL SN 0100-879X J9 BRAZ J MED BIOL RES JI Brazilian J. Med. Biol. Res. PY 1992 VL 25 IS 12 BP 1215 EP 1222 PG 8 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA KG526 UT WOS:A1992KG52600007 PM 1341916 ER PT J AU GERBER, L LAMPERT, M WOOD, C DUNCAN, M DANGELO, T SCHAIN, W MCDONALD, H DANFORTH, D FINDLAY, P GLATSTEIN, E LIPPMAN, ME STEINBERG, SM GORRELL, C LICHTER, A DEMOSS, E AF GERBER, L LAMPERT, M WOOD, C DUNCAN, M DANGELO, T SCHAIN, W MCDONALD, H DANFORTH, D FINDLAY, P GLATSTEIN, E LIPPMAN, ME STEINBERG, SM GORRELL, C LICHTER, A DEMOSS, E TI COMPARISON OF PAIN, MOTION, AND EDEMA AFTER MODIFIED RADICAL-MASTECTOMY VS LOCAL EXCISION WITH AXILLARY DISSECTION AND RADIATION SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE BREAST CANCER; CONSERVATION TREATMENT; LOCAL EXCISION; MASTECTOMY; RADIOTHERAPY; REHABILITATION; SURGERY ID BREAST AB Recent data suggest that prognosis is similar for women with primary breast cancer whether they receive modified radical mastectomy (MRM) or local excision and axillary dissection with radiation (XRT). The effects of either of these treatments on arm mobility, pain, or edema have not been compared, To assess the impact of MRM or XRT on mobility, pain, or edema, we evaluated patients treated in a prospective randomized trial designed to assess prognosis following MRM or XRT. All were provided a standardized physical therapy program including arm mobilization, shoulder strengthening, prevention and treatment of upper extremity eaema, and education about arm function. Patients were evaluated for chest wall pain, arm motion, muscle strength, and edema as determined by circumferential measurements at the wrist, forearm, and arm. Evaluations were performed preoperatively and at yearly anniversaries of their surgery. Women receiving XRT had more chest wall tenderness at 1 and 2 years after surgery than those receiving MRM (P2 < 0.0001 and P2 = 0.0007 respectively). Those receiving MRM were slower to reach their preoperative range of motion (ROM) (p2 = 0.043). Incidence of muscle weakness was similar in both groups. The few patients with local recurrence of tumor had more upper extremity edema than those who did not recur (p2 = 0.085) at 1 year and (p2 = 0.02) at 2 years. In patients who did not develop local recurrence, those who had received XRT had greater but nonsignificant increases in upper extremity circumferential measures compared with those receiving MRM at any anniversary evaluation. Patients receiving MRM and XRT are likely to have some differences in functional outcome. These differences may be important to individuals and be significant in helping them choose between MRM and XRT based upon individual functional needs. C1 NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. NCI,MED BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT BRANCH,BETHESDA,MD 20892. RP GERBER, L (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT REHABIL MED,10-6S235,BETHESDA,MD 20892, USA. NR 11 TC 62 Z9 62 U1 1 U2 2 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. PY 1992 VL 21 IS 2 BP 139 EP 145 DI 10.1007/BF01836960 PG 7 WC Oncology SC Oncology GA HZ936 UT WOS:A1992HZ93600007 PM 1627817 ER PT J AU DAWSON, DA ARCHER, L AF DAWSON, DA ARCHER, L TI GENDER DIFFERENCES IN ALCOHOL-CONSUMPTION - EFFECTS OF MEASUREMENT SO BRITISH JOURNAL OF ADDICTION LA English DT Article ID STATES AB Data from a 1988 survey of US drinking habits and related problems revealed differences in male and female patterns of alcohol consumption. Men were more likely than women to be current drinkers (64 v. 41%), and beer accounted for a larger proportion of their overall intake. Men's average daily ethanol intake was about twice as high as that of women, 17.5 v. 8.9 g. Adjustment for differences in body weight and composition substantially reduced the male-to-female ratio of consumption. Men were more likely than women to be classified as heavy drinkers, and the excess proportion of males so categorized increased with the severity of the measure of heavy drinking. C1 NIAAA,DIV BIOMETRY & EPIDEMIOL,ROCKVILLE,MD 20852. NR 7 TC 90 Z9 91 U1 2 U2 6 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0952-0481 J9 BRIT J ADDICT PD JAN PY 1992 VL 87 IS 1 BP 119 EP 123 PG 5 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA HA914 UT WOS:A1992HA91400022 PM 1543934 ER PT J AU WALSH, CE LIU, JM ANDERSON, SM ROSSIO, JL NIENHUIS, AW YOUNG, NS AF WALSH, CE LIU, JM ANDERSON, SM ROSSIO, JL NIENHUIS, AW YOUNG, NS TI A TRIAL OF RECOMBINANT HUMAN INTERLEUKIN-1 IN PATIENTS WITH SEVERE REFRACTORY APLASTIC-ANEMIA SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; GM-CSF; CELLS; HEMATOPOIESIS; INVITRO; ANEMIA; PROGENITORS; SUPPRESSOR; RECOVERY; RELEASE AB We report here the effects of in vivo administration of recombinant interleukin-1 alpha (rIL-1-alpha) to patients with severe, idiopathic aplastic anaemia. Four patients who were refractory to immunosuppressive therapy and were not bone marrow transplantation candidates received daily doses of 0.03-mu-g/kg and 0.10-mu-g/kg intravenously as 5 d courses. No significant changes in either peripheral blood counts or bone marrow cellularity were observed at either dose during or following therapy. Two patients showed increased numbers of bone marrow progenitor colonies. Lymphocyte phenotyping demonstrated an elevated percentage of CD8+/DR+ activated suppressor T lymphocytes prior to therapy. After rIL-1-alpha administration, the percentage of CD8+/DR+ cells was reduced or returned to normal in all patients. Significant side-effects included fever, rigours, fatigue, headache. and nausea. Transient hypotension was observed at both doses in all patients. These results suggest that while rIL-1-alpha can be safely administered, no significant haematologic improvement was observed in patients with severe aplastic anaemia. C1 NCI,FREDERICK CANC RES & DEV CTR,CLIN IMMUNOL SERV,FREDERICK,MD 21701. NR 28 TC 38 Z9 38 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 JAN PY 1992 VL 80 IS 1 BP 106 EP 110 DI 10.1111/j.1365-2141.1992.tb06408.x PG 5 WC Hematology SC Hematology GA HC130 UT WOS:A1992HC13000017 PM 1536797 ER PT J AU CHIKANZA, IC PETROU, P KINGSLEY, G CHROUSOS, G PANAYI, GS REUMA, O AF CHIKANZA, IC PETROU, P KINGSLEY, G CHROUSOS, G PANAYI, GS REUMA, O TI DEFECTIVE REGULATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS IN RHEUMATOID-ARTHRITIS (RA) IS NOT A CONSEQUENCE OF CHRONIC INFLAMMATION PER-SE SO BRITISH JOURNAL OF RHEUMATOLOGY LA English DT Meeting Abstract C1 FIZIOTERAPIAS INT,BUDAPEST,HUNGARY. GUYS HOSP,RHEUMATOL UNIT,LONDON SE1 9RT,ENGLAND. NICHHD,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0263-7103 J9 BRIT J RHEUMATOL JI Br. J. Rheumatol. PY 1992 VL 31 SU 2 BP 28 EP 28 PG 1 WC Rheumatology SC Rheumatology GA JD274 UT WOS:A1992JD27400048 ER PT J AU OCONNELL, PG SIEGEL, KL STANHOPE, S GERBER, LH AF OCONNELL, PG SIEGEL, KL STANHOPE, S GERBER, LH TI COMPARATIVE GAIT ANALYSIS IN DIFFERENT PATTERNS OF FOOT ARTHRITIS SO BRITISH JOURNAL OF RHEUMATOLOGY LA English DT Meeting Abstract C1 BEAUMONT HOSP,DEPT REHABIL,DUBLIN 9,IRELAND. NIH,DEPT REHABIL,BETHESDA,MD 20892. RI Siegel, Karen Lohmann/B-5898-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0263-7103 J9 BRIT J RHEUMATOL JI Br. J. Rheumatol. PY 1992 VL 31 SU 2 BP 29 EP 29 PG 1 WC Rheumatology SC Rheumatology GA JD274 UT WOS:A1992JD27400049 ER PT J AU COLAIANNI, LA AF COLAIANNI, LA TI THAT VISION THING SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article; Proceedings Paper CT 91ST ANNUAL MEETING OF THE MEDICAL LIBRARY ASSOC CY JUN 04, 1991 CL SAN FRANCISCO, CA SP MED LIB ASSOC AB The 1991 Janet Doe lecturer describes the vision held by the founders of the Medical Library Association of medical information being readily accessible to health professionals no matter how far they were located from major medical centers, and traces the pursuit of this vision to current outreach activities. RP COLAIANNI, LA (reprint author), NATL LIB MED,LIB OPERAT,BETHESDA,MD 20894, USA. NR 29 TC 7 Z9 7 U1 0 U2 0 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA STE 300, 6 N MICHIGAN AVE, CHICAGO, IL 60602 SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD JAN PY 1992 VL 80 IS 1 BP 1 EP 8 PG 8 WC Information Science & Library Science SC Information Science & Library Science GA GZ456 UT WOS:A1992GZ45600001 PM 1537011 ER PT J AU BECK, TJ RUFF, CB SCOTT, WW PLATO, CC TOBIN, JD QUAN, CA AF BECK, TJ RUFF, CB SCOTT, WW PLATO, CC TOBIN, JD QUAN, CA TI SEX-DIFFERENCES IN GEOMETRY OF THE FEMORAL-NECK WITH AGING - A STRUCTURAL-ANALYSIS OF BONE-MINERAL DATA SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE BONE MINERAL ANALYSIS; HIP STRENGTH ANALYSIS; AGE; FEMORAL NECK STRESS ID SENILE OSTEOPOROSIS; FEMUR; AGE; STRENGTH; DENSITY; SPINE AB The greater hip fracture rate among elderly women is generally ascribed to differences in femoral neck strength between the sexes. Strength of a given bone is a function of both its material properties and the magnitudes of mechanical stresses within it. This study examined the hypothesis that these apparent strength differences between the sexes are due to dissimilarities in the restructuring of the femoral neck with age, which result in higher stresses in elderly women. Using Hip Strength Analysis, a computer program developed by the authors, femoral neck cross-sectional geometric properties for stress analyses were derived from bone mineral image data of 409 community living, white subjects ranging from 19 to 93 years of age. Though both sexes show declines in femoral neck bone mineral density (BMD) and cross-sectional area with age, only females show a decline in the cross-sectional moment of inertia (CSMI, a geometric index of bone rigidity). The lack of decline in male CSMI appears to be a result of a small but significant increase in femoral neck girth. Similar age-related changes have been observed in the femoral shaft by others. The net effect of these observed changes is that mechanical stresses in the femoral neck of females appear to increase at three times the rate per decade of those of males. These results lend support to the hypothesis that the higher fracture rate in elderly women is due, at least in part, to elevated levels of mechanical stress, resulting from a combination of greater bone loss and less compensatory geometric restructuring with age. C1 JOHNS HOPKINS MED INST,DEPT CELL BIOL & ANAT,BALTIMORE,MD 21205. JOHNS HOPKINS MED INST,DEPT ORTHOPAED SURG,BALTIMORE,MD 21205. JOHNS HOPKINS MED INST,DEPT BIOMED ENGN,BALTIMORE,MD 21205. FRANCIS SCOTT KEY MED CTR,NIA,GERONTOL RES CTR,APPL PHYSIOL SECT,BALTIMORE,MD 21224. RP BECK, TJ (reprint author), JOHNS HOPKINS MED INST,DEPT RADIOL,600 N WOLFE ST,BALTIMORE,MD 21205, USA. FU NIA NIH HHS [AG08713] NR 19 TC 142 Z9 145 U1 1 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD JAN PY 1992 VL 50 IS 1 BP 24 EP 29 DI 10.1007/BF00297293 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GV959 UT WOS:A1992GV95900007 PM 1739866 ER PT J AU VETTER, U PONTZ, B ZAUNER, E BRENNER, RE SPRANGER, J AF VETTER, U PONTZ, B ZAUNER, E BRENNER, RE SPRANGER, J TI OSTEOGENESIS IMPERFECTA - A CLINICAL-STUDY OF THE 1ST 10 YEARS OF LIFE SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE OI CHILDHOOD; CLINICAL COURSE; CLASSIFICATION ID GENETIC-HETEROGENEITY; MANIFESTATIONS; PHENOTYPE; COLLAGEN AB One hundred twenty-seven children with osteogenesis imperfecta (O.I.) were studied during the first 10 years of life. According to Sillence, 40 patients were assigned to type I, 39 to type III, and 48 to type IV O.I. Centiles for height, weight, and the annual number of fractures could be established for the different types of O.I. The development of the skeletal changes could be documented for the different forms of the disease. At birth, the skeletal changes were significantly more severe in type III than in type IV patients. During the first 10 years of life the number of fractures, extent of skeletal deformities, and growth retardation did not differ between types III and IV. Only fracture nonunion, dentinogenesis imperfecta, and congenital cardiac malformations were more frequent in type III than in type IV. Papillary calcifications of the kidney and kidney stones were diagnosed in 4 type III and 2 type IV patients. Hemihypertrophy of the body developed in 2 type I patients. Although types III and IV patients suffered from severe short stature, serum insulin-like growth factor (IGF) I was in the normal range. C1 UNIV ULM,DEPT PEDIAT,W-7900 ULM,GERMANY. UNIV MUNICH,DEPT PEDIAT,W-8000 MUNICH 2,GERMANY. UNIV MAINZ,DEPT PEDIAT,W-6500 MAINZ,GERMANY. RP VETTER, U (reprint author), NIDR,BONE RES BRANCH,BLDG 30,ROOM 106,BETHESDA,MD 20892, USA. NR 22 TC 77 Z9 77 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD JAN PY 1992 VL 50 IS 1 BP 36 EP 41 DI 10.1007/BF00297295 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GV959 UT WOS:A1992GV95900009 PM 1739868 ER PT J AU SKRTIC, D EANES, ED AF SKRTIC, D EANES, ED TI EFFECT OF MEMBRANE CHOLESTEROL ON CALCIUM-PHOSPHATE FORMATION IN AQUEOUS SUSPENSIONS OF ANIONIC LIPOSOMES SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE CALCIUM PHOSPHATES; LIPOSOMES; CHOLESTEROL; MATRIX VESICLES ID MATRIX VESICLES; EPIPHYSEAL CARTILAGE; MULTILAMELLAR LIPOSOMES; PHOSPHOLIPID-VESICLES AB The present study examined the effect of membrane cholesterol on liposome-mediated calcium phosphate precipitation in metastable aqueous solutions (2.25 mM Ca2+ and 1.5 mM inorganic phosphate) at 22-degrees-C, pH 7.4 and 240 mOsm. The liposomes were prepared from 7:2:X molar mixtures of phosphatidylcholine, dicetylphosphate, and cholesterol (x = 0, 1, 5, or 9) and contained either 0 or 50 mM encapsulated phosphate. The membranes were made permeable to Ca2+ by addition of the cationophore, X-537A. Changes in external Ca2+ concentration were used as the principal monitor of the course of precipitation. Without encapsulated phosphate, 7:2:X liposomes (with or without ionophore) induced no precipitation. With 50 mM encapsulated phosphate and in the presence of ionophore, precipitation significantly depended on the cholesterol level in the membrane. At 0 and 10 mole% cholesterol, precipitate developed rapidly both within and outside the liposomes. At 35 and 50 mole% cholesterol, no observable intraliposomal precipitation occurred, and extraliposomal precipitation started only after an induction period of 24 hours. Delayed extraliposomal precipitation also took place in PO4-containing liposomes without added ionophore. In this latter case, however, cholesterol was essential for this precipitation to occur with the optimum level being around 10 mole%. Suppression of ionophore-mediated intraliposomal precipitation at higher cholesterol levels could be related to the inflexible cholesterol molecules making the membrane more rigid, thereby restricting Ca-ionophore transport. This restriction could be reversed with ethanol. Delayed extraliposomal precipitation in the absence of added ionophore (or at higher cholesterol levels in its presence) could be explained by seeding from low, unobserved levels of intraliposomal precipitate formed during slow, unfacilitated Ca2+ leakage into the liposomal interior. C1 NIST,NIDR,BONE RES BRANCH,RES ASSOCIATE PROGRAM,BLDG 224,ROOM A143,GAITHERSBURG,MD 20899. NR 25 TC 10 Z9 10 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD JAN PY 1992 VL 50 IS 1 BP 55 EP 60 DI 10.1007/BF00297298 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GV959 UT WOS:A1992GV95900012 PM 1739872 ER PT J AU KOPP, JB ROBEY, PG AF KOPP, JB ROBEY, PG TI SODIUM-FLUORIDE DOES NOT INCREASE HUMAN BONE CELL-PROLIFERATION OR PROTEIN-SYNTHESIS INVITRO - REPLY SO CALCIFIED TISSUE INTERNATIONAL LA English DT Letter RP KOPP, JB (reprint author), NIDR,NATL CARIES PROGRAM,BONE RES BRANCH,BETHESDA,MD 20892, USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 12 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD JAN PY 1992 VL 50 IS 1 BP 96 EP 97 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GV959 UT WOS:A1992GV95900020 ER PT B AU JENSEN, RT ZHOU, ZC GU, ZF KITSUKAWA, Y HONDA, T MATON, PN AF JENSEN, RT ZHOU, ZC GU, ZF KITSUKAWA, Y HONDA, T MATON, PN BE TACHE, Y HOLZER, P ROSENFELD, MG TI INTERACTION OF CALCITONIN GENE RELATED PEPTIDES WITH PANCREATIC ACINAR-CELLS AND DISPERSED GASTRIC SMOOTH-MUSCLE CELLS SO CALCITONIN GENE-RELATED PEPTIDE: THE FIRST DECADE OF A NOVEL PLEIOTROPIC NEUROPEPTIDE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Proceedings Paper CT INTERNATIONAL SYMP OF CALCITONIN GENE-RELATED PEPTIDE CY JUL 28-31, 1991 CL GRAZ, AUSTRIA SP NEW YORK ACAD SCI, MINIST SCI & RES AUSTRIA, GOVT PROV STYRIA, CITY GRAZ, NATL SCI FDN, NIDDKD, UNIV CALIF LOS ANGELES, BRAIN RES INST, UNIV CALIF LOS ANGELES SENATE RP JENSEN, RT (reprint author), NIH,DIGEST DIS BRANCH,BLDG 10,ROOM 9C-103,BETHESDA,MD 20892, USA. NR 0 TC 11 Z9 11 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA NEW YORK BN 0-89766-713-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1992 VL 657 BP 268 EP 288 DI 10.1111/j.1749-6632.1992.tb22775.x PG 21 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA BW40M UT WOS:A1992BW40M00023 PM 1379015 ER PT J AU COHEN, PA COHEN, LA AF COHEN, PA COHEN, LA TI CORRELATION OF THE EFFECTS OF ALKYL SUBSTITUENTS ON THE BASICITIES OF INDOLES SO CANADIAN JOURNAL OF CHEMISTRY-REVUE CANADIENNE DE CHIMIE LA English DT Note DE ALKYLINDOLES; CARBON BASICITY; FREE ENERGY CORRELATION; SUBSTITUENT EFFECTS; N-ALKYL EFFECT ID ACID AB Alkyl groups at C-2 of indole increase basicity at the site of protonation, C-3, while alkyl groups at C-3 decrease basicity. These opposing effects can be incorporated, for both the isomeric mono- and 2,3-dialkylindoles, into a single linear free energy correlation, pK(a) = -10.05-SIGMA-sigma - 3.94, in which SIGMA-sigma = sigma(p)+(C-2) + 0.60[sigma(m)+(C-3) + 0.08D(s) - 0.084] and D(s) is the double bond stabilization parameter at C-3. An analogous correlation for N-methylindoles, pK(a) = -8.64-SIGMA-sigma - 2.80, reveals that the effect of N-alkylation on basicity is predictable but not additive. C1 NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. NR 14 TC 3 Z9 3 U1 0 U2 1 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0008-4042 J9 CAN J CHEM JI Can. J. Chem.-Rev. Can. Chim. PD JAN PY 1992 VL 70 IS 1 BP 282 EP 284 DI 10.1139/v92-039 PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA JD652 UT WOS:A1992JD65200039 ER PT J AU SOKOLOFF, L AF SOKOLOFF, L TI ENERGY-METABOLISM AND EFFECTS OF ENERGY DEPLETION OR EXPOSURE TO GLUTAMATE SO CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT SYMP ON THE PHYSIOLOGY, PHARMACOLOGY, AND BIOPHYSICS OF GANGLIONIC TRANSMISSION CY AUG 12-14, 1991 CL UNIV ALBERTA, EDMONTON, CANADA SP INT BRAIN RES ORG HO UNIV ALBERTA DE GLYCOGEN; GLYCOLYSIS; OXIDATIVE METABOLISM; ACIDOSIS; ENERGY METABOLISM ID BRAIN AB The entire program of the first day of the IBRO satellite meeting entitled Ions, Water, and Energy in Brain Cells was devoted to the subject of energy. There were three sessions on the topics of energy metabolism, activation, and development and pathological conditions. followed by a final general discussion on the contents of the day's topics. During this general discussion there were spirited exchanges on the role of glycogen in the energy metabolism of the brain, on the metabolic source of the energy consumed by functional activity e.g., glycolytic or oxidative energy metabolism, and on the sources of the acid-equivalents that are responsible for the tissue acidosis accompanying cerebral hypoxia. Despite the arguments pro and con presented on all of the issues that were discussed, it is doubtful that a consensus was achieved on most of the issues. RP SOKOLOFF, L (reprint author), NIMH,CEREBRAL METAB LAB,BLDG 36,ROOM 1A-05,BETHESDA,MD 20892, USA. NR 19 TC 13 Z9 13 U1 0 U2 0 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. PY 1992 VL 70 SU S BP S107 EP S112 PG 6 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA KL246 UT WOS:A1992KL24600016 PM 1363528 ER PT J AU DAWSON, NA WILDING, G WEISS, RB MCLEOD, DG LINEHAN, WM FRANK, JA JACOB, JL GELMANN, EP AF DAWSON, NA WILDING, G WEISS, RB MCLEOD, DG LINEHAN, WM FRANK, JA JACOB, JL GELMANN, EP TI A PILOT TRIAL OF CHEMOHORMONAL THERAPY FOR METASTATIC PROSTATE CARCINOMA SO CANCER LA English DT Article ID CHEMOTHERAPY; CANCER AB Fifteen patients with previously untreated metastatic prostate cancer were treated on a pilot trial with a combination of maximal androgen blockade plus intermittent cytotoxic therapy after androgen priming to stimulate cell division. Androgen blockage was carried out using a gonadotropin-releasing hormone analog (leuprolide) plus a nonsteroidal antiandrogen (flutamide). Carboplatin (CBDCA)(800 mg/m2) was given intravenously every 28 days, preceded for 3 days and followed for 3 days by androgen treatment with fluoxymesterone (5 mg orally twice a day), during which time flutamide was discontinued. Three patients (20%) achieved a complete response (CR), and eight patients (53.3%) achieved a partial response (PR). Four patients (26.7%) had stable disease (SD). The median progression-free survival (PFS) time was 31 months. Nine of 15 patients (60%) remain alive with a median follow-up time of 42+ months (range, 22 to 54 months). Grade 4 thrombocytopenia and Grades 3 or 4 leukopenia were experienced in 87% and 80% of patients, respectively, requiring dose reductions of CBDCA in 85% of the cycles. Six of 15 patients experienced a flare in bone pain with androgen priming. There were no associated spinal cord compressions; however, exclusion of impending spinal cord compression was required before entrance on study. C1 WALTER REED ARMY MED CTR,DEPT UROL,WASHINGTON,DC 20307. NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. RP DAWSON, NA (reprint author), WALTER REED ARMY MED CTR,DEPT MED,HEMATOL ONCOL SERV,WASHINGTON,DC 20307, USA. NR 21 TC 12 Z9 12 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 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 1992 VL 69 IS 1 BP 213 EP 218 DI 10.1002/1097-0142(19920101)69:1<213::AID-CNCR2820690135>3.0.CO;2-V PG 6 WC Oncology SC Oncology GA GW428 UT WOS:A1992GW42800034 PM 1727665 ER PT J AU GOFFMAN, TE DEWAN, R ARAKAKI, R GORDEN, P OLDFIELD, EH GLATSTEIN, E AF GOFFMAN, TE DEWAN, R ARAKAKI, R GORDEN, P OLDFIELD, EH GLATSTEIN, E TI PERSISTENT OR RECURRENT ACROMEGALY - LONG-TERM ENDOCRINOLOGIC EFFICACY AND NEUROLOGIC SAFETY OF POSTSURGICAL RADIATION-THERAPY SO CANCER LA English DT Article ID PITUITARY-ADENOMAS; IRRADIATION; MANAGEMENT; SURGERY AB As in other clinics, pituitary surgery was definitive treatment in less than 50% of cases of acromegaly treated at one institution over several decades. From 1965 to 1989, 24 acromegalic patients who had noncurative pituitary surgery received radiation therapy at the National Institutes of Health, with a basal human growth hormone level of greater than 5 ng/ml as the criterion for active disease. Using megavoltage irradiation, more than 60% of these patients stabilized at a normal hormonal range, and the overwhelming majority had decreasing growth hormone levels with time. No major side effects of irradiation were encountered except panhypopituitarism of varying degrees. The authors evolved a policy of surgery as the first option, followed by irradiation for patients with postoperative growth hormone levels more than 5 ng/ml. C1 NIDDKD,DIABET BRANCH,BETHESDA,MD. NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. RP GOFFMAN, TE (reprint author), NCI,RADIAT ONCOL BRANCH,B3B69,BLDG 10,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 15 TC 30 Z9 31 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 1992 VL 69 IS 1 BP 271 EP 275 DI 10.1002/1097-0142(19920101)69:1<271::AID-CNCR2820690145>3.0.CO;2-U PG 5 WC Oncology SC Oncology GA GW428 UT WOS:A1992GW42800044 PM 1727672 ER PT J AU SZEKERES, T CHOCHUNG, YS WEBER, G AF SZEKERES, T CHOCHUNG, YS WEBER, G TI ACTION OF TIAZOFURIN AND 8-CL-CAMP IN HUMAN COLON AND PANCREATIC-CANCER CELLS SO CANCER BIOCHEMISTRY BIOPHYSICS LA English DT Article DE 8-CL-CAMP; TIAZOFURIN; C-MYC; C-RAS; HT-29 HUMAN COLON CANCER; BXPC-3 AND PANC-1 HUMAN PANCREATIC CANCER ID CYCLIC-AMP ANALOGS; IMP DEHYDROGENASE; HEPATOMA-CELLS; GROWTH; DIFFERENTIATION; LEUKEMIA; 2-BETA-D-RIBOFURANOSYLTHIAZOLE-4-CARBOXAMIDE; CHEMOTHERAPY; MODULATION; MALIGNANCY AB Tiazofurin and 8-Cl-cAMP are novel chemotherapeutic agents shown to be effective against various cancer cells in vitro and in vivo. They act through distinct mechanisms that might modulate the signal transduction pathway, which causes growth inhibition, differentiation and down-regulation of c-ras and c-myc oncogene expression. We examined the effects of tiazofurin and 8-Cl-cAMP on colony formation of HT-29 human colon cancer and BxPC-3 and PANC-1 human pancreatic cancer cell lines. The IC50 of 8-Cl-cAMP was 0.1 and 0.2 muM in the pancreatic and colon cancer cell lines, respectively, and tiazofurin yielded IC50s from 4 (PANC-1) to 18 muM (HT-29). Simultaneous incubation with 8-Cl-cAMP and tiazofurin had additive effects on the inhibition of colony formation in the three examined cell lines. These results indicate possible clinical usefulness of a combination of tiazofurin and 8-Cl-cAMP in the treatment of colon and pancreatic carcinomas. C1 INDIANA UNIV,SCH MED,EXPTL ONCOL LAB,INDIANAPOLIS,IN 46202. NCI,CELLULAR BIOCHEM SECT,BETHESDA,MD 20892. FU NCI NIH HHS [CA-42510] NR 31 TC 11 Z9 11 U1 0 U2 0 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 0305-7232 J9 CANCER BIOCHEM BIOPH JI Cancer Biochem. Biophys. PY 1992 VL 13 IS 2 BP 67 EP 74 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA JY667 UT WOS:A1992JY66700001 PM 1364229 ER PT J AU JANZ, S KRUMBIEGEL, M GAWRISCH, K AF JANZ, S KRUMBIEGEL, M GAWRISCH, K TI THE FLUIDITY OF DOPC BILAYERS AND MEMBRANE-FRACTIONS PREPARED FROM MURINE PLASMACYTOMA CELLS IS UNCHANGED AFTER INCORPORATION OF PRISTANE (2,6,10,14-TETRAMETHYLPENTADECANE) AS ASSESSED BY FLUORESCENCE POLARIZATION ANALYSIS SO CANCER BIOCHEMISTRY BIOPHYSICS LA English DT Article DE ALKANES; PRISTANE; DOPC; MEMBRANE FLUIDITY; MURINE PLASMACYTOMA ID LIPID FLUIDITY; LYMPHOCYTES; DNA AB The nature of the plasmacytomagenic activity of pristane (2.6,10,14-tetramethylpentadecane) is poorly defined. However, evidence for tumor promoting properties of pristane has recently come forward that includes direct cellular effects on B lymphocytes; i.e., the plasmacytoma precursor cell. Bly et al. (Cancer Biochem. Biophys. 11, 1990, 145-154) observed changed membrane fluidities in lymphocytes after administration of pristane in vivo. We measured steady-state fluorescence polarization using DPH (1,6-diphenyl-1,3,5-hexatriene) and APC(L) (1-acyl-2-112-(9-anthryl)-11-trans-dodecenoyl]-sn-glycero-3-phosphocholine) as probes in DOPC (L-alpha-dioleoylphosphatidylcholin) model membranes and membrane fractions derived from plasmacytoma cells after incorporation of pristane in vitro. In a previous investigation, we verified the in vitro uptake of pristane into DOPC bilayers under the conditions employed here (Gawrisch and Janz, Biochim. Biophys. Acta 1070, 1991, 409-418). However, neither in DOPC bilayers nor in plasmacytoma membrane fractions could we detect changes in fluorescence polarization after in vitro incorporation of pristane within reasonable error limits. Therefore, we suggest that the observed alterations in membrane fluidity in lymphocytes from pristane-treated animals are the indirect result of the in vivo treatment but not a direct effect of pristane on membrane fluidity. C1 NCI,LMMB MEMBRANE STRUCT & FUNCT,BETHESDA,MD 20892. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. RP JANZ, S (reprint author), NCI,GENET LAB,BLDG 37,ROOM 2B09,BETHESDA,MD 20892, USA. NR 23 TC 4 Z9 4 U1 1 U2 2 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 0305-7232 J9 CANCER BIOCHEM BIOPH JI Cancer Biochem. Biophys. PY 1992 VL 13 IS 2 BP 85 EP 92 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA JY667 UT WOS:A1992JY66700003 PM 1343851 ER PT J AU HEINEMAN, EF ZAHM, SH MCLAUGHLIN, JK VAUGHT, JB HRUBEC, Z AF HEINEMAN, EF ZAHM, SH MCLAUGHLIN, JK VAUGHT, JB HRUBEC, Z TI A PROSPECTIVE-STUDY OF TOBACCO USE AND MULTIPLE-MYELOMA - EVIDENCE AGAINST AN ASSOCIATION SO CANCER CAUSES & CONTROL LA English DT Article DE CIGARETTES; MULTIPLE MYELOMA; TOBACCO; UNITED-STATES; VETERANS AB The relationship between the use of cigarettes and other tobacco products and the risk of multiple myeloma was examined in a cohort of nearly 250,000 American veterans followed prospectively for 26 years. Compared with men who had never used tobacco, the risk of death from myeloma was not increased among current (relative risk [RR] = 0.9, 95 percent confidence interval [CI] = 0.8 - 1.2) or former (RR = 1.0, CI = 0.8 -1.3) cigarette smokers, nor among users of chewing tobacco or snuff (RR = 1.0, CI = 0.4 -2.3). Risk was only slightly and nonsignificantly increased among pipe or cigar smokers (RR = 1.2, CI = 0.9 -1.5). There was no indication of increasing risk with amount of tobacco used or earlier age at first use. With over 90 percent power to detect a 30 percent increased risk of this tumor occurring among current cigarette smokers, this study provides the strongest evidence to date against an association of cigarette smoking with multiple myeloma. RP HEINEMAN, EF (reprint author), NCI,6130 EXECUT BLVD,ROOM 418,ROCKVILLE,MD 20892, USA. RI Zahm, Shelia/B-5025-2015 NR 0 TC 26 Z9 26 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 JAN PY 1992 VL 3 IS 1 BP 31 EP 36 DI 10.1007/BF00051909 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA HA707 UT WOS:A1992HA70700005 PM 1536911 ER PT J AU HSING, AW HOOVER, RN MCLAUGHLIN, JK COCHIEN, HT WACHOLDER, S BLOT, WJ FRAUMENI, JF AF HSING, AW HOOVER, RN MCLAUGHLIN, JK COCHIEN, HT WACHOLDER, S BLOT, WJ FRAUMENI, JF TI ORAL-CONTRACEPTIVES AND PRIMARY LIVER-CANCER AMONG YOUNG-WOMEN SO CANCER CAUSES & CONTROL LA English DT Article DE CASE-CONTROL STUDY; LIVER CANCER; ORAL CONTRACEPTIVE USE; UNITED-STATES AB The association of oral contraceptive use with liver cancer was examined in a study of 76 deaths from primary liver cancer, 22 deaths from cancer of the intrahepatic bile ducts, and 629 controls among women aged 25 to 49 years. The subjects in the study are from the 1986 National Mortality Followback Survey, which included a questionnaire sent or administered to the next-of-kin of almost 20,000 deceased individuals in the United States. Information on a number of lifestyle factors was collected, including questions on oral contraceptive use. Increased risks of primary liver cancer were found for ever-users (odds ratio [OR] = 1.6, 95 percent confidence interval [CI] = 0.9-2.6), and for long-term (greater-than-or-equal-to 1 0 years) users (OR = 2.0, CI = 0.8-4.8) of oral contraceptives. When the analysis was restricted to subjects whose spouse or parent was the respondent, more pronounced risks were seen for ever-users (OR = 2.7, CI = 1.4-5.3) and long-term users (OR = 4.8, CI = 1.714. 0). No clear excess risk was found for cancer of the intrahepatic bile ducts. This study, the largest to date, adds to the number of investigations demonstrating an increased risk of primary liver cancer with use, particularly long-term use, of oral contraceptives. RP HSING, AW (reprint author), NCI,EXECUT PLAZA N,ROOM 415,BETHESDA,MD 20892, USA. NR 0 TC 31 Z9 31 U1 1 U2 1 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 JAN PY 1992 VL 3 IS 1 BP 43 EP 48 DI 10.1007/BF00051911 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA HA707 UT WOS:A1992HA70700007 PM 1536912 ER PT J AU BROWN, LM EVERETT, GD GIBSON, R BURMEISTER, LF SCHUMAN, LM BLAIR, A AF BROWN, LM EVERETT, GD GIBSON, R BURMEISTER, LF SCHUMAN, LM BLAIR, A TI SMOKING AND RISK OF NON-HODGKINS-LYMPHOMA AND MULTIPLE-MYELOMA SO CANCER CAUSES & CONTROL LA English DT Article DE CASE-CONTROL STUDY; CIGARETTES; EPIDEMIOLOGY; ETIOLOGY; MULTIPLE MYELOMA; NON-HODGKINS LYMPHOMA; SMOKING; TOBACCO; UNITED-STATES AB Population-based case-control interview studies of 622 White men with non-Hodgkin's lymphoma and 820 controls from Iowa and Minnesota (United States) and 173 White men with multiple myeloma and 452 controls from Iowa offered the opportunity to investigate the relationship of these cancers with smoking. Risks were significantly elevated for all lymphoma (odds ratio [OR] = 1.4), high-grade lymphoma (OR = 2.3), and unclassified lymphoma (OR = 2.8) for cigarette smokers. Dose-response gradients were not seen with intensity of cigarette use, but risks for these subtypes were greatest for cigarette smokers of longest duration. Similar elevations in risks were seen for tobacco users. The risk of multiple myeloma was not significantly elevated for either tobacco users or cigarette smokers. The findings from this study confirm the lack of an association between smoking and multiple myeloma and provide some support for an association between tobacco use and certain subtypes of non-Hodgkin's lymphoma. RP BROWN, LM (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,ROOM 415C,BETHESDA,MD 20892, USA. FU NIEHS NIH HHS [ES 03099] NR 0 TC 85 Z9 86 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 JAN PY 1992 VL 3 IS 1 BP 49 EP 55 DI 10.1007/BF00051912 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA HA707 UT WOS:A1992HA70700008 PM 1536913 ER PT J AU CANTOR, KP LYNCH, CF JOHNSON, D AF CANTOR, KP LYNCH, CF JOHNSON, D TI BLADDER-CANCER, PARITY, AND AGE AT 1ST BIRTH SO CANCER CAUSES & CONTROL LA English DT Article DE BLADDER CANCER; HORMONES; REPRODUCTIVE FACTORS; PARITY; UNITED-STATES AB The excess of bladder cancer in males (M:F ratio of 4:1 in the United States) is not explained fully by gender differences in smoking habits or occupational exposures. Laboratory studies suggest that some androgenic hormones stimulate (or do not inhibit) oncogenesis in bladder tissue, and that estrogenic hormones have the opposite effect. These observations suggest that bladder cancer risk in females may be modified by sex hormones which undergo profound changes during and following pregnancy. Mail-questionnaire data from 317 incident female cases, and 833 population-based controls in Iowa were used to measure the effect of parity and maternal age at first birth on bladder cancer risk. Parous women were at decreased risk relative to nulliparous women (odds ratio [OR] = 0.67, 95 percent confidence interval [CI] = 0.44-1.00), after adjustment for age, tobacco use, and previous bladder infection. The overall risk reduction was restricted to women who had never smoked (OR = 0.51, CI = 0.30-0.88), with no apparent effect of parity among ever-smokers (OR = 0.93, CI = 0.49-1.77). Risk appeared to decrease with increasing age at first birth, but did not vary with increasing parity after the first birth. Our findings are consistent with the hypothesis that oncogenesis in transitional cell tissue of the human bladder is influenced by sex hormones, and that hormonal changes related to pregnancy thereby can decrease risk. RP CANTOR, KP (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EXECUT PLAZA N,SUITE 443,BETHESDA,MD 20892, USA. FU NCI NIH HHS [5 KO7 CA01181-04, N01-CP-51026, N01-CP-85614] NR 0 TC 59 Z9 60 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 JAN PY 1992 VL 3 IS 1 BP 57 EP 62 DI 10.1007/BF00051913 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA HA707 UT WOS:A1992HA70700009 PM 1536914 ER PT J AU DIETER, MP MARONPOT, RR JAMESON, CW WARD, SM AF DIETER, MP MARONPOT, RR JAMESON, CW WARD, SM TI THE EFFECTS OF IODINATED GLYCEROL, TRICHLORFON, AND ACETAMINOPHEN ON TUMOR PROGRESSION IN A FISCHER RAT LEUKEMIA TRANSPLANT MODEL SO CANCER DETECTION AND PREVENTION LA English DT Article DE F344 RAT LEUKEMIA; INVIVO TRANSPLANT MODEL; ACETAMINOPHEN; TRICHLORFON; IODINATED GLYCEROL AB Sixty-day bioassays of iodinated glycerol, trichlorfon, and acetaminophen were conducted using a leukemia transplant model in 6- to 8-week-old F344 rats to investigate the potential of these chemicals to affect tumor progression. The chemicals were administered in the drinking water at doses that approximated those used in previously conducted 2-year carcinogenesis studies. Simultaneous with dose administration, half of a group of young, healthy, syngeneic rats were given subcutaneous transplants of mononuclear cells derived from spleens of leukemic donors. Variables used to quantitate tumor progression included body weight, spleen weight, white blood cell (WBC) and red blood cell (RBC) counts, packed cell volume, hemoglobin concentration, and platelet counts. Iodinated glycerol at 1.25 or 2.5 mg/ml caused a greater increase in leukocytosis in dosed transplant recipients in comparison to that experienced by undosed recipients: trichlorfon at 2.5 or 5.0 mg/ml enhanced splenomegaly and induced greater reductions in RBC parameters in dosed recipients in comparison to that experienced by undosed recipients. Acetaminophen at 3.0 and 6.0 mg/ml resulted in insignificant but dose-related increases in spleen weight and leukocytosis only in the female rat transplant recipients, as was observed in 2-year studies. Based on results from the short-term leukemia transplant model, data from 2-year carcinogenicity studies, and structure-activity considerations, exposure to iodinated glycerol and trichlorfon was more strongly associated with the expression of leukemia than exposure to acetaminophen. The potential carcinogenicity of each of these chemicals should be taken into consideration when calculating estimates of risk and decisions for their use. RP DIETER, MP (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0361-090X J9 CANCER DETECT PREV JI Cancer Detect. Prev. PY 1992 VL 16 IS 3 BP 173 EP 183 PG 11 WC Oncology SC Oncology GA JV359 UT WOS:A1992JV35900004 PM 1458507 ER PT J AU KNELLER, RW GUO, WD HSING, AW CHEN, JS BLOT, WJ LI, JY FORMAN, D FRAUMENI, JF AF KNELLER, RW GUO, WD HSING, AW CHEN, JS BLOT, WJ LI, JY FORMAN, D FRAUMENI, JF TI RISK-FACTORS FOR STOMACH-CANCER IN 65 CHINESE COUNTIES SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GASTRIC-CANCER; HELICOBACTER-PYLORI; ANTIBODY PREVALENCE; SERUM SELENIUM; DIET; ASSOCIATION; MORTALITY; FREQUENCY; ALBUMIN AB Stomach cancer mortality data were compared with dietary and biochemical data from 65 Chinese counties to provide clues to reasons for the marked geographic variation of stomach cancer mortality rates in China. Sex-specific correlation and multivariate regression analyses showed significant positive associations with consumption of salted vegetables and eggs, prevalence of antibodies to Helicobacter pylori, and levels of plasma albumin; and significant negative associations with intake of green vegetables and levels of plasma selenium and beta-carotene. Limitations of ecological data preclude causal inferences, but these findings suggest factors that may contribute to making stomach cancer the leading cause of cancer death in China and other countries. C1 NCI,ROOM 415,EXECUT PLAZA N,BETHESDA,MD 20892. CHINESE ACAD PREVENT MED,INST NUTR & FOOD HYG,BEIJING,PEOPLES R CHINA. CHINESE ACAD MED SCI,INST CANC,DEPT EPIDEMIOL,BEIJING,PEOPLES R CHINA. IMPERIAL CANC RES FUND,CANC EPIDEMIOL UNIT,OXFORD OX2 6HE,ENGLAND. FU NCI NIH HHS [5R01-CA33638-05] NR 39 TC 66 Z9 67 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN-FEB PY 1992 VL 1 IS 2 BP 113 EP 118 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA HN951 UT WOS:A1992HN95100003 PM 1306092 ER PT J AU REZANKA, LJ ROJKO, JL NEIL, JC AF REZANKA, LJ ROJKO, JL NEIL, JC TI FELINE LEUKEMIA-VIRUS - PATHOGENESIS OF NEOPLASTIC DISEASE SO CANCER INVESTIGATION LA English DT Review ID C-MYC-GENE; T-CELL RECEPTOR; AVIAN MYELOCYTOMATOSIS VIRUS; LONG TERMINAL REPEAT; APLASTIC-ANEMIA RETROVIRUS; BURKITT-LYMPHOMA CELLS; DNA-BINDING PROTEIN; SARCOMA-VIRUS; ANTIGEN RECEPTOR; NUCLEOTIDE-SEQUENCE C1 OHIO STATE UNIV,CTR RETROVIRUS RES,DEPT VET PATHOBIOL,1925 COFFEY RD,COLUMBUS,OH 43210. OHIO STATE UNIV,CTR COMPREHENS CANC,COLUMBUS,OH 43210. NCI,BIOL LAB,BETHESDA,MD 20892. WOLFSON INST MOLEC PATHOL,BEATSON INST CANC RES,GLASGOW G63 1BD,SCOTLAND. FU NIAID NIH HHS [AI-25722]; NIDDK NIH HHS [DK-41066] NR 181 TC 41 Z9 41 U1 0 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 1992 VL 10 IS 5 BP 371 EP 389 DI 10.3109/07357909209024796 PG 19 WC Oncology SC Oncology GA JQ734 UT WOS:A1992JQ73400005 PM 1327427 ER PT J AU JOHNSON, BE AF JOHNSON, BE TI BEST PAPERS ON LUNG-CANCER SO CANCER INVESTIGATION LA English DT Bibliography RP JOHNSON, BE (reprint author), USN HOSP,NCI,BETHESDA,MD 20814, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 1992 VL 10 IS 5 BP 491 EP 492 DI 10.3109/07357909209024809 PG 2 WC Oncology SC Oncology GA JQ734 UT WOS:A1992JQ73400018 PM 1393696 ER PT J AU LUETHY, JD HOLBROOK, NJ AF LUETHY, JD HOLBROOK, NJ TI ACTIVATION OF THE GADD153 PROMOTER BY GENOTOXIC AGENTS - A RAPID AND SPECIFIC RESPONSE TO DNA DAMAGE SO CANCER RESEARCH LA English DT Article ID IMMUNODEFICIENCY VIRUS TYPE-1; PROTEIN CROSS-LINKING; MAMMALIAN-CELLS; PLASMINOGEN-ACTIVATOR; UV-IRRADIATION; PHORBOL ESTER; C-FOS; REPAIR; INDUCTION; GENE AB Accumulation of gadd153 mRNA is strongly stimulated in mammalian cells by treatments which arrest growth or damage DNA (A. J. Fornace, Jr. et al., Mol. Cell. Biol., 9. 4196-4203, 1989). In previous studies, we demonstrated that the increased expression of gadd153 following treatment with several DNA-damaging agents was mediated transcriptionally (J. D. Luethy et al., J. Biol. Chem., 265:16521-16526, 1990). To better define the specificity of this response, we have established a sensitive reporter system in which we have stably integrated a chimeric gene containing the gadd153 promoter linked to the coding region of the chloramphenicol acetyltransferse (CAT) gene into the genome of HeLa cells. Transcriptional activation from the gadd153 promoter was monitored by determining levels of CAT activity in cellular lysates prepared from gadd153CAT/HeLa cells treated with a variety of agents. The gadd153 promoter was strongly activated by a broad spectrum of genotoxic agents including UV-mimetic agents, DNA-cross-linking and alkylating agents, DNA intercalators, and topoisomerase inhibitors. Of the DNA-damaging agents tested, only X-irradiation and bleomycin treatments failed to induce gadd153 promoter activity. Agents which inhibit replication and cell division and agents which otherwise result in cytotoxicity or growth arrest also had little influence on gadd153 promoter activity. Expression of the gadd153CAT chimeric gene in xeroderma pigmentosum Group A cells, which are deficient in nucleotide excision DNA repair of pyrimidine dimers, was maximally induced at UV doses at least 6-fold lower than those required for similar induction in repair-proficient HeLa cells. However, the methyl methanesulfonate-induced gadd153 promoter activities were similar in both cell lines. Novobiocin pretreatment inhibited both UV- and methyl methanesulfonate-induced gadd153CAT expression. Collectively, these data indicate that: (a) the gadd153 promoter is activated rapidly and specifically by DNA damage; (b) the altered DNA structure is the inducing signal for the activation of the signal transduction pathway responsible for enhanced gadd153 expression; and (c) regulation of gadd153 by growth arrest is distinct from that of DNA damage. Thus, the gadd153CAT/HeLa cells are a useful model for examining the molecular mechanisms associated with the response to DNA damage and provide a reporter system for the screening of potential genotoxic agents. C1 NIA,GERONTOL RES CTR,MOLEC GENET LAB,BALTIMORE,MD 21224. NR 41 TC 163 Z9 169 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 1992 VL 52 IS 1 BP 5 EP 10 PG 6 WC Oncology SC Oncology GA GW846 UT WOS:A1992GW84600002 PM 1727386 ER PT J AU BOARMAN, DM ALLEGRA, CJ AF BOARMAN, DM ALLEGRA, CJ TI INTRACELLULAR METABOLISM OF 5-FORMYL TETRAHYDROFOLATE IN HUMAN BREAST AND COLON CELL-LINES SO CANCER RESEARCH LA English DT Article ID HIGH-DOSE LEUCOVORIN; THYMIDYLATE SYNTHASE INHIBITION; FOLINIC ACID; FOLATE POOLS; CANCER-CELLS; METHOTREXATE POLYGLUTAMATES; ADENOCARCINOMA XENOGRAFTS; 5-FLUOROURACIL; CARCINOMA; FLUOROURACIL AB This report describes the intracellular metabolism of 5-formyltetrahydrofolate into the various one-carbon substituted folate and polyglutamate pools in a human breast (MCF-7) and colon (HCT 116) carcinoma cell line. Metabolism into the one-carbon substituted pools was found to be time and dose dependent over a concentration range up to 50-mu-M. A 3-fold increase in total intracellular folate was noted over a 50-fold concentration range (1-50-mu-M) of 5-formyltetrahydrofolate tested in the colon cell line, while in the breast line, a 6-fold increase was detected over a 500-fold concentration range (0.1-50-mu-M). The level of 5, 10-methylenetetrahydrofolate, which was detectable only in the breast cell line, was found to increase by a factor of 10 (1.8 pmol/mg to 17.9 pmol/mg) over the concentration range studied. The majority of metabolism was into the 10-formyltetrahydrofolate and tetrahydrofolate pools in the breast cells and into the 5-methyltetrahydrofolate pool in the colon cells. Polyglutamation was also time and dose dependent, with a significant proportion of the total pool represented by the higher polyglutamate forms (Glu3-Glu5) after 24 h of continuous exposure to 5-formyl tetrahydrofolate. Pentaglutamate was the highest level noted in both cell lines. The intracellular half-life of the polyglutamate forms was inversely related to the length of the polyglutamate tail with half-lives of 71, 131, 143, 441, and 1167 min for the mono- through pentaglutamate, respectively. Finally, up to a 20:1 ratio of the biologically inactive (6R) isomer to active (6S) isomer of 5-formyltetrahydrofolate resulted in no effect on metabolism into the one-carbon substituted folate pools and only minimal decreases in metabolism to the polyglutamate forms. These studies suggest that prolonged exposure to even relatively low doses of 5-formyltetrahydrofolate may be optimal for intracellular metabolism to the most biologically relevant forms for ternary complex formation with thymidylate synthase and fluorodeoxyuradylate, since longer exposures result in a greater accumulation of the higher polyglutamates. C1 NCI,DIV CANC TREATMENT,MED BRANCH,BLDG 10,ROOM 12N226,BETHESDA,MD 20892. NR 36 TC 53 Z9 53 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 1992 VL 52 IS 1 BP 36 EP 44 PG 9 WC Oncology SC Oncology GA GW846 UT WOS:A1992GW84600007 PM 1370075 ER PT J AU HORNUNG, RL PEARSON, JW BECKWITH, M LONGO, DL AF HORNUNG, RL PEARSON, JW BECKWITH, M LONGO, DL TI PRECLINICAL EVALUATION OF BRYOSTATIN AS AN ANTICANCER AGENT AGAINST SEVERAL MURINE TUMOR-CELL LINES - INVITRO VERSUS INVIVO ACTIVITY SO CANCER RESEARCH LA English DT Article ID PROTEIN KINASE-C; HUMAN MALIGNANT-LYMPHOMAS; ANTI-NEOPLASTIC AGENTS; PHORBOL ESTER RECEPTOR; BUGULA-NERITINA; ANTINEOPLASTIC AGENTS; GROWTH-INHIBITION; LEUKEMIA-CELLS; RENAL-CANCER; DIFFERENTIATION AB The have examined the ability of bryostatin 1 to inhibit the in vitro growth and in vivo development of a panel of four murine tumors of diverse tissue origins. A wide range of antiproliferative responses was observed for the four tumors. At 100 ng/ml the in vitro growth of the Renca renal adenocarcinoma, the B16 melanoma, the M5076 reticulum cell sarcoma, and the L10A B-cell lymphoma were inhibited by 0, 40, 40, and 94% respectively. All three cell lines sensitive to bryostatin in vitro responded to multiple dose, 1-mu-g/injection/day in vivo i.p., bryostatin therapy. Only the in vitro resistant Renca tumor failed to respond to bryostatin in vivo. The correlation between in vitro and in vivo antitumor efficacy suggests a direct mechanism of antitumor activity for bryostatin. Both local regional therapy (M5076 i.p.) and systemic therapy (B16 lung metastases and L10A s.c. tumors) with bryostatin were successful at prolonging survival time. Multiple i.p. doses of bryostatin at a minimum level of 0.5-1.0-mu-g/injection Ar ere required to observe significant in vivo antitumor effects. The success of in vivo administration of bryostatin in mice bearing 8-10-mm s.c. masses of L10A lymphoma (5-10 x 10(9) and our further observation that five of a panel of six human B-cell lymphoma cell lines were sensitive to the growth inhibitory effects of bryostatin in vitro suggest that bryostatin may be effective in treating lymphoid malignancies in humans. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,FREDERICK,MD 21701. RP HORNUNG, RL (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21701, USA. FU NCI NIH HHS [N01-CO-74102] NR 30 TC 124 Z9 124 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 1992 VL 52 IS 1 BP 101 EP 107 PG 7 WC Oncology SC Oncology GA GW846 UT WOS:A1992GW84600017 PM 1727368 ER PT J AU POIRIER, MC REED, E LITTERST, CL KATZ, D GUPTABURT, S AF POIRIER, MC REED, E LITTERST, CL KATZ, D GUPTABURT, S TI PERSISTENCE OF PLATINUM-AMMINE-DNA ADDUCTS IN GONADS AND KIDNEYS OF RATS AND MULTIPLE TISSUES FROM CANCER-PATIENTS SO CANCER RESEARCH LA English DT Article ID OVARIAN-CANCER; CIS-DIAMMINEDICHLOROPLATINUM; CISPLATIN; CHEMOTHERAPY; FIBROBLASTS; TUMORS; REPAIR; MOUSE; CELLS AB The persistence of platinum-DNA adducts was investigated using normal rats as well as tissues from cancer patients receiving either cis-diamminedichloroplatinum(II) (cisplatin) or diamminecyclobutanedicarboxylatoplatinum(II) (carboplatin) for cancer chemotherapy. These studies used an enzyme-linked immunosorbent assay, established with a rabbit anti-cisplatin-DNA that is specific for intrastrand platinum-DNA adducts. The gonads and kidneys of male and female rats, sites for antitumor activity and toxicity, respectively, were monitored for cisplatin-DNA adduct formation after a single dose of drug and during multiple-dose exposures (once a wk for 3 wk). DNA adducts were measured by enzyme-linked immunosorbent assay 4 h and 2, 4, 7, and 14 days after administering a single i.v. injection of 8 mg/kg of cisplatin. Adduct profiles in renal tissues were similar in both males and females with adduct levels increasing between 4 h and 2 days, decreasing between Days 2 and 7, and stable between Days 7 and 14. In both sexes, levels of kidney DNA adduct measured 7 to 14 days after cisplatin injection comprised about 30% of the highest (Day 2) value. In testes and ovaries, adduct removal was complete by 4 days, and 40 to 50% of adducts present at Day 2 persisted until Days 7 and 14. A study of multiple dosing showed that adducts in renal and testicular DNA from rats given three weekly doses of 5 mg/kg of cisplatin had different accumulation profiles. In the testis there was a 2-fold accumulation of adduct after the third dose, while in the kidney adducts dropped with repeated dosing. In humans, the persistence of platinum-DNA adducts was studied in tissues from eight cancer patients who received their last dose of cisplatin or carboplatin chemotherapy between 1 day and 15 mo before autopsy. The patients had either ovarian cancer, breast cancer, or lymphoma, and the tissues studied included ovarian tumor, bone marrow, kidney, liver, spleen, lymph node, peripheral nerve, and brain. When samples were available from tumor tissues and from bone marrow within the same patient, adduct levels were similar in the two tissues. In addition, adducts were persistent for many months, since half of the individuals received their most recent platinum-drug therapy 7 to 15 mo before death. Overall, these studies demonstrate a widespread distribution and high degree of platinum-DNA adduct persistence in both animal and human tissues subsequent to cisplatin or carboplatin treatment. C1 NCI,DIV CANC ETIOL,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NINCDS,OFF CLIN DIRECTOR,BETHESDA,MD 20892. NIAID,DIV AIDS,DEV THERAPEUT BRANCH,BETHESDA,MD 20892. RP POIRIER, MC (reprint author), NCI,DIV CANC TREATMENT,MED BRANCH,BLDG 37,ROOM 3B25,BETHESDA,MD 20892, USA. NR 26 TC 67 Z9 67 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 1992 VL 52 IS 1 BP 149 EP 153 PG 5 WC Oncology SC Oncology GA GW846 UT WOS:A1992GW84600025 PM 1727376 ER PT J AU CHANG, K PAI, LH BATRA, JK PASTAN, I WILLINGHAM, MC AF CHANG, K PAI, LH BATRA, JK PASTAN, I WILLINGHAM, MC TI CHARACTERIZATION OF THE ANTIGEN (CAK1) RECOGNIZED BY MONOCLONAL-ANTIBODY K1 PRESENT ON OVARIAN CANCERS AND NORMAL MESOTHELIUM SO CANCER RESEARCH LA English DT Article ID PSEUDOMONAS EXOTOXIN; CARCINOMA; CELLS; RADIOIMMUNOASSAY; SURFACE; IMMUNOTOXINS AB K1 is a monoclonal antibody that reacts with a cell surface antigen (CAK1) found in human mesothelia and nonmucinous ovarian tumors. In this article, the characteristics of the CAK1 antigen have been examined in detail. Using immunofluorescence microscopy, we have found that the CAK1 signal is removed from the cell surface by treatment with proteases or by phosphatidylinositol-phospholipase C, but not by neuraminidase and beta-galactosidase. The phosphatidylinositol-phospholipase C-released material was found to contain the CAK1 antigen which was detected by a competition radioimmunoassay. The phosphatidylinositol-phospholipase C-released CAK1 antigen was examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting and found to be a approximately 40 kDa protein. The CAK1-K1 antibody complex remains on the cell surface and is poorly internalized, as shown by an acid wash immunofluorescence internalization assay. An immunotoxin composed of K1 and Lys-PE40, a mutant form of Pseudomonas exotoxin lacking the cell binding domain, was not cytotoxic, supporting the conclusion that the CAK1-K1 antibody complex is not internalized. However, an immunotoxin composed of K1 and native Pseudomonas exotoxin was selectively cytotoxic to cells expressing the CAK1 antigen. This cytotoxicity is due to the fact that domain I of Pseudomonas exotoxin promotes internalization of antigens which are not internalized or bound to antibody alone. Our results suggest that CAK1 is a polypeptide that is expressed on mesothelial cells and many ovarian cancers, and that K1 may be useful as a targeting agent for the immunotherapy of human ovarian cancer. C1 NCI,MOLEC BIOL LAB,BLDG 37,ROOM 4E16,BETHESDA,MD 20892. NR 28 TC 88 Z9 88 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 1992 VL 52 IS 1 BP 181 EP 186 PG 6 WC Oncology SC Oncology GA GW846 UT WOS:A1992GW84600030 PM 1727378 ER PT J AU HASLER, CM ACS, G BLUMBERG, PM AF HASLER, CM ACS, G BLUMBERG, PM TI SPECIFIC BINDING TO PROTEIN-KINASE-C BY INGENOL AND ITS INDUCTION OF BIOLOGICAL RESPONSES SO CANCER RESEARCH LA English DT Article ID EPIDERMAL GROWTH-FACTOR; PHORBOL 12,13-DIBUTYRATE BINDING; MOUSE-BRAIN CYTOSOL; TUMOR PROMOTERS; INTERCELLULAR COMMUNICATION; ALTERED DIFFERENTIATION; ORNITHINE DECARBOXYLASE; ESTER PHARMACOPHORE; INDUCED INHIBITION; CELLS AB We have examined the ability of ingenol to bind to and activate protein kinase C and to induce similar responses to the phorbol esters in biological systems. The rationale was that ingenol possesses the critical functionalities of the phorbol ester pharmacophore with the exception of the hydrophobic domain; it might therefore possess weak potency, although previous reports had indicated that ingenol was biologically inactive. Our data demonstrate that ingenol indeed binds to protein kinase C with a K(i) of 30-mu-M and activates the enzyme. In addition, ingenol was biologically active in 3 separate cell systems, showing effects similar to the phorbol esters on morphological change, cell-cell communication, epidermal growth factor binding, arachidonic acid metabolite release, and ornithine decarboxylase activity. The 50% effective concentration values for the biological activity of ingenol were between 30-mu-M and 1 mM, varying somewhat with the cell system and type of response. The biological activity of ingenol in general supports the proposed models of the phorbol ester pharmacophore and imposes additional experimental constraints that the modeling must satisfy. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BLDG 373B25,BETHESDA,MD 20892. NR 42 TC 45 Z9 45 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 1992 VL 52 IS 1 BP 202 EP 208 PG 7 WC Oncology SC Oncology GA GW846 UT WOS:A1992GW84600033 PM 1727380 ER PT J AU MAEHLE, L METCALF, RA RYBERG, D BENNETT, WP HARRIS, CC HAUGEN, A AF MAEHLE, L METCALF, RA RYBERG, D BENNETT, WP HARRIS, CC HAUGEN, A TI ALTERED P53 GENE STRUCTURE AND EXPRESSION IN HUMAN EPITHELIAL-CELLS AFTER EXPOSURE TO NICKEL SO CANCER RESEARCH LA English DT Note ID MAMMALIAN-CELLS; TUMOR-ANTIGEN; RAS ONCOGENE; TRANSFORMATION; IMMORTALIZATION; CHROMOSOME-17; CARCINOMA; PROTEIN; KIDNEY; LUNG AB The carcinogenicity of certain nickel compounds is well known. We have previously shown that human kidney epithelial cells were immortalized by treatment with Ni(II) and in cooperation with the v-Ha-ras oncogene transformed the cells to acquire tumorigenicity in athymic nude mice. Immunocytochemistry and sequence analysis of DNA from the nickel-immortalized cells revealed abnormal p53 expression and a T --> C transition mutation in codon 238. These data are consistent with the hypothesis that Ni(II)-induced mutation in the p53 gene can be involved in the escape from senescence of kidney epithelial cells. C1 NATL INST OCCUPAT HLTH,DEPT TOXICOL,POB 8149 DEP,N-0033 OSLO 1,NORWAY. NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 33 TC 43 Z9 45 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 1992 VL 52 IS 1 BP 218 EP 221 PG 4 WC Oncology SC Oncology GA GW846 UT WOS:A1992GW84600035 PM 1727381 ER PT J AU ROBERTS, AB SPORN, MB AF ROBERTS, AB SPORN, MB TI MECHANISTIC INTERRELATIONSHIPS BETWEEN 2 SUPERFAMILIES - THE STEROID RETINOID RECEPTORS AND TRANSFORMING GROWTH-FACTOR-BETA SO CANCER SURVEYS LA English DT Article ID HUMAN-BREAST-CANCER; RAT VENTRAL PROSTATE; TGF-BETA; DIFFERENTIAL REGULATION; REVERSIBLE INHIBITION; ADRENOCORTICAL-CELLS; MOUSE KERATINOCYTES; EMBRYONAL CARCINOMA; ANDROGEN PRODUCTION; GENE-EXPRESSION RP ROBERTS, AB (reprint author), NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892, USA. NR 78 TC 91 Z9 94 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0261-2429 J9 CANCER SURV JI Cancer Surv. PY 1992 VL 14 BP 205 EP 220 PG 16 WC Oncology SC Oncology GA JF078 UT WOS:A1992JF07800015 PM 1330304 ER PT J AU MUNGER, K SCHEFFNER, M HUIBREGTSE, JM HOWLEY, PM AF MUNGER, K SCHEFFNER, M HUIBREGTSE, JM HOWLEY, PM TI INTERACTIONS OF HPV E6 AND E7 ONCOPROTEINS WITH TUMOR SUPPRESSOR GENE-PRODUCTS SO CANCER SURVEYS LA English DT Review ID HUMAN PAPILLOMAVIRUS TYPE-16; SV40 LARGE-T; RETINOBLASTOMA SUSCEPTIBILITY GENE; ADENOVIRUS E1A PROTEINS; PRIMARY HUMAN KERATINOCYTES; CARCINOMA CELL-LINES; RAT 3Y1 CELLS; CERVICAL-CARCINOMA; TRANSFORMING ACTIVITY; MUTATIONAL ANALYSIS RP MUNGER, K (reprint author), NCI, TUMOUR VIRUS BIOL LAB, BETHESDA, MD 20892 USA. RI Scheffner, Martin/K-2940-2012; OI Scheffner, Martin/0000-0003-2229-0128; Munger, Karl/0000-0003-3288-9935 NR 118 TC 206 Z9 208 U1 1 U2 6 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0261-2429 J9 CANCER SURV JI Cancer Surv. PY 1992 VL 12 BP 197 EP 217 PG 21 WC Oncology SC Oncology GA HP484 UT WOS:A1992HP48400012 PM 1322242 ER PT J AU RAO, CT PITHA, J LINDBERG, B LINDBERG, J AF RAO, CT PITHA, J LINDBERG, B LINDBERG, J TI DISTRIBUTION OF SUBSTITUENTS IN O-(2-HYDROXYPROPYL) DERIVATIVES OF CYCLOMALTOOLIGOSACCHARIDES (CYCLODEXTRINS) - INFLUENCE OF INCREASING SUBSTITUTION, OF THE BASE USED IN THE PREPARATION, AND OF MACROCYCLIC SIZE SO CARBOHYDRATE RESEARCH LA English DT Article ID HYDROXYPROPYL-BETA-CYCLODEXTRIN AB Samples of O-(2-hydroxypropyl) derivatives of cyclomaltoheptaose (beta-cyclodextrin) with increasing substitution were prepared by withdrawing aliquots at different times from a reaction mixture containing cyclomaltoheptaose and an excess of (S)-propylene oxide in 0.39M aqueous sodium hydroxide. The distributions of substituents between the different molecules and between the different alpha-D-glucopyranosyl residues in these samples were determined by mass spectrometry and methylation analysis, respectively. The solubilities of the samples and their association constants with phenolphthalein were also determined. The relative reactivities at O-2 and O-3 versus O-6, calculated using Spurlin's equations, decreased with increasing degree of substitution, probably because of steric hindrance. No significant differences were observed when different strong bases were used as promoters of the hydroxypropylation of cyclomaltoheptaose. The hydroxypropylation of cyclomaltohexaose (alpha-cyclodextrin) and cyclomalto-octaose (gamma-cyclodextrin) was briefly investigated. C1 UNIV STOCKHOLM,ARRHENIUS LAB,DEPT ORGAN CHEM,S-10691 STOCKHOLM,SWEDEN. RP RAO, CT (reprint author), NIA,GRC,BALTIMORE,MD 21224, USA. NR 10 TC 35 Z9 37 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD JAN PY 1992 VL 223 BP 99 EP 107 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA HB800 UT WOS:A1992HB80000009 ER PT J AU MILEI, J STORINO, R ALONSO, GF BEIGELMAN, R VANZULLI, S FERRANS, VJ AF MILEI, J STORINO, R ALONSO, GF BEIGELMAN, R VANZULLI, S FERRANS, VJ TI ENDOMYOCARDIAL BIOPSIES IN CHRONIC CHAGASIC CARDIOMYOPATHY - IMMUNOHISTOCHEMICAL AND ULTRASTRUCTURAL FINDINGS SO CARDIOLOGY LA English DT Article DE CHAGASIC CARDIOMYOPATHY; ENDOMYOCARDIAL BIOPSIES; CHRONIC INFLAMMATION; MORPHOMETRY; ELECTRON MICROSCOPY; IMMUNOHISTOCHEMISTRY; LYMPHOCYTES-T; LYMPHOCYTES-B; CHRONIC MYOCARDITIS ID TRYPANOSOMA-CRUZI CARDIOMYOPATHY; MAST-CELLS; DISEASE; MYOCARDITIS; DIAGNOSIS; PATHOLOGY; TISSUE; HEART AB Mononuclear cellular infiltrates and extensive fibrosis, with or without apical ventricular aneurysms, are the usual morphological findings in chronic chagasic cardiomyopathy. These lesions are thought to be mediated by immune phenomena rather than by continuing parasitic invasion of the heart. In the present report, we correlated clinical, immunohistochemical and ultrastructural findings in 30 endomyocardial biopsies from patients with chronic chagasic cardiomyopathy. In 12 of these biopsies, immunocytochemical techniques were used to identify and count leukocytes (common leukocyte antigen, CLA), T lymphocytes (UCHL-1 antibody) and B lymphocytes (L-26 antibody). The biopsy specimens showed variable degrees of myocardial hypertrophy and mononuclear infiltrates. No tissue forms of trypanosomes were found. The endocardium averaged 24 +/- 12.6 mum (mean +/- SD) in thickness. The mean myocyte diameter was 20 +/- 7.33 mum. The hearts were severely fibrotic containing a mean of 24.1 +/- 12.8% of fibrous tissue (range 8.2-49%), mast cells were scarce. Mononuclear cell infiltrates were found in 25 of the 30 biopsies. In 12 biopsies, immunohistochemical studies showed that the majority of the lymphocytes were T lymphocytes and associated with necrotic or degenerating myocytes. 10 of the 12 biopsy samples showed 5 or more CLA-positive mononuclear cells/high power field. In these 10 patients, T and B lymphocytes represented 32 and 13% of the total mononuclear infiltrating cells, respectively. The remaining cells were monocytes and macrophages. C1 HOSP JUAN A FERNANDEZ,BUENOS AIRES,ARGENTINA. INST ESTUDIOS ONCOL,BUENOS AIRES,ARGENTINA. NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. RP MILEI, J (reprint author), CADDIOPSIS,TUCUMAN 2163,4-B,RA-1050 BUENOS AIRES,ARGENTINA. OI MILEI, JOSE/0000-0003-4029-5993 NR 42 TC 21 Z9 21 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PY 1992 VL 80 IS 5-6 BP 424 EP 437 DI 10.1159/000175035 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JZ135 UT WOS:A1992JZ13500017 PM 1451131 ER PT B AU DAVIDSON, WF PIERCE, JH HOLMES, KL AF DAVIDSON, WF PIERCE, JH HOLMES, KL BE HERZENBERG, LA HAUGHTON, G RAJEWSKY, K TI EVIDENCE FOR A DEVELOPMENTAL RELATIONSHIP BETWEEN CD5+ B-LINEAGE CELLS AND MACROPHAGES SO CD5 B CELLS IN DEVELOPMENT AND DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Proceedings Paper CT CONF ON CD5 B-CELLS IN DEVELOPMENT AND DISEASE CY JUN 03-06, 1991 CL PALM BEACH GARDENS, FL SP NEW YORK ACAD SCI, NIAID, MARION MERRELL DOW, MERCK SHARP & DOHME RES LABS, SYNTEX RES RP DAVIDSON, WF (reprint author), NCI,GENET LAB,BETHESDA,MD 20892, USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA NEW YORK BN 0-89766-701-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1992 VL 651 BP 112 EP 129 PG 18 WC Biochemistry & Molecular Biology; Immunology; Pathology SC Biochemistry & Molecular Biology; Immunology; Pathology GA BW41S UT WOS:A1992BW41S00014 ER PT B AU KEHRL, JH RIECKMANN, P KOZLOW, E FAUCI, AS AF KEHRL, JH RIECKMANN, P KOZLOW, E FAUCI, AS BE HERZENBERG, LA HAUGHTON, G RAJEWSKY, K TI LYMPHOKINE PRODUCTION BY B-CELLS FROM NORMAL AND HIV-INFECTED INDIVIDUALS SO CD5 B CELLS IN DEVELOPMENT AND DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Proceedings Paper CT CONF ON CD5 B-CELLS IN DEVELOPMENT AND DISEASE CY JUN 03-06, 1991 CL PALM BEACH GARDENS, FL SP NEW YORK ACAD SCI, NIAID, MARION MERRELL DOW, MERCK SHARP & DOHME RES LABS, SYNTEX RES RP KEHRL, JH (reprint author), NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892, USA. NR 0 TC 15 Z9 15 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA NEW YORK BN 0-89766-701-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1992 VL 651 BP 220 EP 227 PG 8 WC Biochemistry & Molecular Biology; Immunology; Pathology SC Biochemistry & Molecular Biology; Immunology; Pathology GA BW41S UT WOS:A1992BW41S00030 ER PT B AU BERTIN, PA MARTI, GE AF BERTIN, PA MARTI, GE BE HERZENBERG, LA HAUGHTON, G RAJEWSKY, K TI EXPRESSION OF IMMUNOGLOBULIN HEAVY-CHAIN VARIABLE GENE (V(H)) IN B-CHRONIC LYMPHOCYTIC-LEUKEMIA (B-CLL) AND B-PROLYMPHOCYTIC LEUKEMIA (B-PLL) CELL-LINES - RESTRICTED USAGE OF V(H)3 FAMILY SO CD5 B CELLS IN DEVELOPMENT AND DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Proceedings Paper CT CONF ON CD5 B-CELLS IN DEVELOPMENT AND DISEASE CY JUN 03-06, 1991 CL PALM BEACH GARDENS, FL SP NEW YORK ACAD SCI, NIAID, MARION MERRELL DOW, MERCK SHARP & DOHME RES LABS, SYNTEX RES RP BERTIN, PA (reprint author), NIH,US FDA,CTR BIOL EVALUAT & RES,DIV BIOCHEM & BIOPHYS,BETHESDA,MD 20892, USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA NEW YORK BN 0-89766-701-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1992 VL 651 BP 464 EP 464 PG 1 WC Biochemistry & Molecular Biology; Immunology; Pathology SC Biochemistry & Molecular Biology; Immunology; Pathology GA BW41S UT WOS:A1992BW41S00059 ER PT B AU MARTI, GE FAGUET, G BERTIN, P AGEE, J WASHINGTON, G RUIZ, S CARTER, P ZENGER, V VOGT, R NOGUCHI, P AF MARTI, GE FAGUET, G BERTIN, P AGEE, J WASHINGTON, G RUIZ, S CARTER, P ZENGER, V VOGT, R NOGUCHI, P BE HERZENBERG, LA HAUGHTON, G RAJEWSKY, K TI CD20 AND CD5 EXPRESSION IN B-CHRONIC LYMPHOCYTIC-LEUKEMIA SO CD5 B CELLS IN DEVELOPMENT AND DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Proceedings Paper CT CONF ON CD5 B-CELLS IN DEVELOPMENT AND DISEASE CY JUN 03-06, 1991 CL PALM BEACH GARDENS, FL SP NEW YORK ACAD SCI, NIAID, MARION MERRELL DOW, MERCK SHARP & DOHME RES LABS, SYNTEX RES RP MARTI, GE (reprint author), NIH,US FDA,CTR BIOL EVALUAT & RES,DIV BIOCHEM & BIOPHYS,BETHESDA,MD 20892, USA. NR 0 TC 22 Z9 22 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA NEW YORK BN 0-89766-701-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1992 VL 651 BP 480 EP 483 PG 4 WC Biochemistry & Molecular Biology; Immunology; Pathology SC Biochemistry & Molecular Biology; Immunology; Pathology GA BW41S UT WOS:A1992BW41S00064 ER PT J AU BIRD, GS TAKEMURA, H THASTRUP, O PUTNEY, JW MENNITI, FS AF BIRD, GS TAKEMURA, H THASTRUP, O PUTNEY, JW MENNITI, FS TI MECHANISMS OF ACTIVATED CA2+ ENTRY IN THE RAT PANCREATOMA CELL-LINE, AR4-2J SO CELL CALCIUM LA English DT Article ID LACRIMAL ACINAR-CELLS; SUBSTANCE-P RECEPTORS; INOSITOL 1,4,5-TRISPHOSPHATE; TUMOR PROMOTER; CALCIUM ENTRY; INTRACELLULAR CALCIUM; AR42J CELLS; FREE CA-2+; THAPSIGARGIN; INCREASE AB The characteristics of Ca2+ entry activated by surface receptor agonists and membrane depolarization were studied in the rat pancreatoma cell line, AR4-2J. Ca2+ mobilization activated by substance P, bombesin, or muscarinic receptor stimulation was found to involve both Ca2+ release and entry. In addition, depolarization of the surface membrane of AR4-2J cells with elevated concentrations of K+ activated Ca2+ entry. Ca2+ entry induced by membrane depolarization was inhibited by the L-channel antagonist, nimodipine, while that due to surface receptor agonists was not inhibited by this agent. The microsomal Ca2+-ATPase inhibitor, thapsigargin, caused both depletion of the agonist-sensitive intracellular Ca2+ pool and sustained Ca2+ influx indistinguishable from that produced by bombesin or methacholine. These results confirm that, unlike the pancreatic acinar cells from which they are presumably derived, AR4-2J cells express voltage-sensitive, dihydropyridine-inhibitable Ca2+ channels. However, in contrast to previous reports with this cell line, in the AR4-2J cells in use in our laboratory, and under our experimental conditions, surface receptor agonists (including substance P) do not cause Ca2+ influx through voltage-sensitive Ca2+ channels. Instead, we conclude that agonist-activated Ca2+ mobilization is initiated by (1,4,5)IP3-mediated intracellular Ca2+ release and that Ca2+ influx is regulated primarily, if not exclusively, by the state of depletion of the (1,4,5)IP3-sensitive intracellular Ca2+ pool. C1 NIEHS,CELLULAR & MOLEC PHARMACOL LAB,CALCIUM REGULAT SECT,POB 12233,RES TRIANGLE PK,NC 27709. UNIV COPENHAGEN HOSP,RIGSHOSP,DEPT CLIN CHEM,DK-2100 COPENHAGEN,DENMARK. SYMBION COPENHAGEN SCI PK,THROMBOSIS GRP,COPENHAGEN,DENMARK. OI Menniti, Frank/0000-0003-2612-9534 NR 36 TC 29 Z9 31 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 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD JAN PY 1992 VL 13 IS 1 BP 49 EP 58 DI 10.1016/0143-4160(92)90029-R PG 10 WC Cell Biology SC Cell Biology GA GX934 UT WOS:A1992GX93400006 PM 1371721 ER PT J AU BHARGAVA, M JOSEPH, A KNESEL, J HALABAN, R LI, Y PANG, S GOLDBERG, I SETTER, E DONOVAN, MA ZARNEGAR, R MICHALOPOULOS, GA NAKAMURA, T FALETTO, D ROSEN, EM AF BHARGAVA, M JOSEPH, A KNESEL, J HALABAN, R LI, Y PANG, S GOLDBERG, I SETTER, E DONOVAN, MA ZARNEGAR, R MICHALOPOULOS, GA NAKAMURA, T FALETTO, D ROSEN, EM TI SCATTER FACTOR AND HEPATOCYTE GROWTH-FACTOR - ACTIVITIES, PROPERTIES, AND MECHANISM SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID FULMINANT HEPATIC-FAILURE; SMOOTH-MUSCLE RELEASES; HEPATOPOIETIN-A; MOLECULAR-CLONING; EPITHELIAL-CELLS; TUMOR-CELLS; HEPARIN; PURIFICATION; PROTEIN; FIBROBLASTS AB Scatter factor (SF) was first identified as a fibroblast-derived protein which disperses (ie., "scatters") cohesive colonies of epithelium. SF-like proteins were found in human smooth muscle cell conditioned medium, amniotic fluid, and placental tissue. SFs markedly stimulate migration of epithelial, carcinoma, and vascular endothelial cell types at picomolar concentrations. Hepatocyte growth factors (HGFs) were originally described as platelet- and serum-derived proteins which stimulate hepatocyte DNA synthesis. Partial amino acid sequence data for mouse and human SFs indicate significant homology with HGFs. We used biological, biochemical, and immunological assays to evaluate and compare the activities, properties, and mechanisms of action of mouse SF, human SF (fibroblast or placenta derived), and recombinant human HGF (hrHGF). We report the following findings: (a) mouse SF exhibits species-related differences in biological activities relative to the human factors; (b) human SF and hrHGF show significant overlap in biological activities (ie., hrHGF stimulates motility of multiple normal and carcinoma cell types, whereas human SF stimulates DNA synthesis in several normal cell types); (c) the three factors contain common antigenic determinants; and (d) all three proteins stimulate rapid phosphorylation of tyrosine residues on the c-met protooncogene protein product (the putative receptor for HGF) and on another protein with M(r) 110,000. A few biological and immunological differences between human Sfs and hrHGF were observed. These may reflect minor variations in amino acid sequence or posttranslational modification related to the sources of the factors. Taken as a whole, our findings suggest that by structural, functional, immunological, and mechanistic criteria, human SF and human HGF are essentially identical. C1 YALE UNIV,SCH MED,DEPT THERAPEUT RADIOL,333 CEDAR ST,NEW HAVEN,CT 06510. YALE UNIV,SCH MED,DEPT DERMATOL,NEW HAVEN,CT 06510. LONG ISL JEWISH MED CTR,DIV RADIAT ONCOL,NEW HYDE PK,NY 11042. DUKE UNIV,MED CTR,DEPT PATHOL,DURHAM,NC 27710. KYUSHU UNIV,FAC SCI 33,DEPT BIOL,FUKUOKA 812,JAPAN. NCI,FREDERICK CANC RES CTR,FREDERICK,MD 21702. FU NCI NIH HHS [R01 CA50516] NR 34 TC 135 Z9 144 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 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD JAN PY 1992 VL 3 IS 1 BP 11 EP 20 PG 10 WC Cell Biology SC Cell Biology GA GZ013 UT WOS:A1992GZ01300002 PM 1534687 ER PT J AU OCONNOR, PM FERRIS, DK WHITE, GA PINES, J HUNTER, T LONGO, DL KOHN, KW AF OCONNOR, PM FERRIS, DK WHITE, GA PINES, J HUNTER, T LONGO, DL KOHN, KW TI RELATIONSHIPS BETWEEN CDC2 KINASE, DNA CROSS-LINKING, AND CELL-CYCLE PERTURBATIONS INDUCED BY NITROGEN-MUSTARD SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID FISSION YEAST; SACCHAROMYCES-CEREVISIAE; PROTEIN-KINASE; G2 ARREST; MOLECULAR-BASIS; HUMAN HOMOLOG; RAD9 GENE; M-PHASE; MECHANISM; PRODUCT AB M phase-promoting factor (MPF) consists of a p34cdc2 (cdc2) kinase and cyclin B complex which in its active form promotes G2 to M transition. The role of MPF in G2 arrest following DNA damage, however, has remained largely uncharacterized. We have investigated whether nitrogen mustard (HN2) interfered with either the formation of MPF or its activation. For this purpose, we measured cdc2 kinase activity relative to cdc2 and cyclin B protein turnover and the phosphorylation status of cdc2. Studies were performed in two exceptional human lymphoma cell lines, which differed in HN2 sensitivity by 5-fold (CA46, 50% growth-inhibitory dose = 1.0-mu-m; JLP119, 50% growth-inhibitory dose = 0.2-mu-m) but exhibited virtually identical DNA interstrand and DNA-protein cross-link exposure. Following HN2 treatment, CA46 cells ceased to enter mitosis and exhibited a marked delay in G2 phase. Failure to enter mitosis paralleled inhibition of cdc2 kinase. Inhibition was not due to decreased levels of cdc2 or cyclin B protein; rather, G2 arrest correlated with the accumulation of both tyrosine-phosphorylated cdc2 and cyclin B. These findings implied that G2 arrest resulted from a down-regulation of the processes that activate MPF. We also found that JLP119 cells, within a few hours of mitosis at the time of drug treatment, evaded checkpoint control and continued cell division unabated by DNA damage. Furthermore, despite similar DNA cross-link exposure, JLP119 cells within the window of checkpoint control were more susceptible to S phase delay than CA46 cells. Altered cell cycle responses correlated with the greater susceptibility of JLP119 cells to the cytotoxic effects of HN2. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. SALK INST BIOL STUDIES,MOLEC BIOL & VIROL LAB,SAN DIEGO,CA 92138. PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD. RP OCONNOR, PM (reprint author), NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,BETHESDA,MD 20892, USA. OI Pines, Jonathon/0000-0002-5227-6004 NR 42 TC 106 Z9 108 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 JAN PY 1992 VL 3 IS 1 BP 43 EP 52 PG 10 WC Cell Biology SC Cell Biology GA GZ013 UT WOS:A1992GZ01300005 PM 1534688 ER PT J AU VENESIO, T TAVERNA, D HYNES, NE DEED, R MACALLAN, D CIARDIELLO, F VALVERIUS, EM SALOMON, DS CALLAHAN, R MERLO, G AF VENESIO, T TAVERNA, D HYNES, NE DEED, R MACALLAN, D CIARDIELLO, F VALVERIUS, EM SALOMON, DS CALLAHAN, R MERLO, G TI THE INT-2 GENE-PRODUCT ACTS AS A GROWTH-FACTOR AND SUBSTITUTES FOR BASIC FIBROBLAST GROWTH-FACTOR IN PROMOTING THE DIFFERENTIATION OF A NORMAL MOUSE MAMMARY EPITHELIAL-CELL LINE SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID BETA-CASEIN GENE; PROTO-ONCOGENE INT-2; SERUM-FREE MEDIUM; FACTOR RECEPTOR; BREAST-CANCER; TUMOR VIRUS; EXPRESSION; TRANSFORMATION; TUMORIGENESIS; STIMULATION AB We have investigated the effect of basic fibroblast growth factor (bFGF) and the related int-2 gene on the growth, transformation, and differentiation of HC11 mouse mammary epithelial cells. We show that in HC11 cells infected with int-2 retroviral expression vectors, the int-2 protein can function as a bFGF-like growth factor in stimulating: (a) HC11 cell proliferation in monolayer, (b) anchorage-independent growth in soft agar, and (c) soft agar growth of the bFGF-responsive SW13 tumor cell line. These effects are observed irrespective of whether the int-2 protein is expressed in its wild-type form or is linked to a signal peptide. A candidate bFGF receptor, which is the product of the flg gene and which may recognize the int-2 protein, is expressed at high levels in HC11 cells. Following epidermal growth factor or bFGF priming and subsequent treatment with lactogenic hormones, all of the int-2 infected and the parental HC11 cells synthesize similar levels of beta-casein. However, the autocrine expression of int-2 in HC11 cells abrogates their requirement for either exogenous epidermal growth factor or bFGF priming. These data suggest that, in HC11 cells, the growth factor activity of the int-2 gene is indistinguishable from that of bFGF and does not interfere with the mammary cell differentiation program associated with lactogenesis. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. FRIEDRICH MIESCHER INST,CH-4002 BASEL,SWITZERLAND. ST BARTHOLOMEWS HOSP,IMPERIAL CANC RES FUND LABS,LONDON EC1A 7BE,ENGLAND. RI taverna, daniela/J-8358-2016 OI Ciardiello, Fortunato/0000-0002-3369-4841; taverna, daniela/0000-0002-6365-527X NR 54 TC 19 Z9 19 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 JAN PY 1992 VL 3 IS 1 BP 63 EP 71 PG 9 WC Cell Biology SC Cell Biology GA GZ013 UT WOS:A1992GZ01300007 PM 1376141 ER PT J AU JANSON, LW SELLERS, JR TAYLOR, DL AF JANSON, LW SELLERS, JR TAYLOR, DL TI ACTIN-BINDING PROTEINS REGULATE THE WORK PERFORMED BY MYOSIN-II MOTORS ON SINGLE ACTIN-FILAMENTS SO CELL MOTILITY AND THE CYTOSKELETON LA English DT Article DE MOTILITY ASSAY; GELATION; SOLATION ID SMOOTH-MUSCLE MYOSIN; ALPHA-ACTININ; CYTOPLASMIC STRUCTURE; INVITRO MOTILITY; CONTRACTION; MOVEMENT; SOLATION; MODEL; CELLS; PHOSPHORYLATION AB Regulation of actin/myosin II force generation by calcium [Kamm and Stull, Annu. Rev. Physiol. 51:299-313, 1989] and phosphorylation of myosin II light chains [Sellers and Adelstein, "The Enzymes," Vol. 18, Orlando, FL: Academic Press, 1987, pp. 381-418] is well established. However, additional regulation of actin/myosin II force generation/contraction may result from actin-binding proteins [Stossel et al., Ann. Rev. Cell Biol. 1:353-402, 1985; Pollard and Cooper, Ann. Rev. Biochem. 55:987-1035, 1986] as they affect the gel state of the actin cytomatrix [reviewed in Taylor and Condeelis, Int. Rev. Cytol., 56:57-143, 1979]. Regulation of the gel state of actin may determine whether an isotonic or isometric contraction results from the interaction between myosin and actin. We have extended the single actin filament motility assay of Kron and Spudich [Proc. Natl. Acad. Sci. U.S.A. 83:6272-6276, 1986] by including filamin or alpha-actinin on the substrate with myosin II to examine how actin-crosslinking proteins regulate the movements of single actin filaments. Increasing amounts of actin-crosslinking proteins inhibit filament velocity and decrease the number of filaments moving. Reversal of crosslinking yields increased velocities and numbers of moving filaments. These results support the solation-contraction coupling hypothesis [see Taylor and Fechheimer, Phil. Trans. Soc. London B 299:185-197, 1982] which proposes that increased crosslinking of actin inhibits myosin-based contraction. This study also illustrates the potentially varied roles of different actin-crosslinking proteins and offers a novel method to examine actin-binding protein activity and their regulation of motility at the single molecule level. C1 CARNEGIE MELLON UNIV,DEPT BIOL SCI,PITTSBURGH,PA 15213. CARNEGIE MELLON UNIV,CTR LIGHT MICROSCOPE IMAGING & BIOTECHNOL,PITTSBURGH,PA 15213. NHLBI,MOLEC CARDIOL LAB,BETHESDA,MD 20892. FU NIAMS NIH HHS [AR-32461]; NIGMS NIH HHS [5T32GM08067-08] NR 28 TC 41 Z9 42 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 0886-1544 J9 CELL MOTIL CYTOSKEL JI Cell Motil. Cytoskeleton PY 1992 VL 22 IS 4 BP 274 EP 280 DI 10.1002/cm.970220407 PG 7 WC Cell Biology SC Cell Biology GA JF189 UT WOS:A1992JF18900006 PM 1516149 ER PT J AU SARIG, S HIRSCH, D AZOURY, R WEISS, TA KATZ, I KRUTH, HS AF SARIG, S HIRSCH, D AZOURY, R WEISS, TA KATZ, I KRUTH, HS TI APATITE-CHOLESTEROL AGGLOMERATES IN HUMAN ATHEROSCLEROTIC LESIONS SO CELLS AND MATERIALS LA English DT Article DE CALCIUM PHOSPHATE; APATITE; CHOLESTEROL; ATHEROSCLEROTIC LESION; SCANNING ELECTRON MICROSCOPY; SECONDARY ELECTRON IMAGING; BACK SCATTERING ELECTRON IMAGING; ENERGY DISPERSIVE X-RAY ANALYSIS; CATHODOLUMINESCENCE ID POLYENE ANTIBIOTICS; FILIPIN; DEPOSITS; CALCIUM AB The purpose of this study was to examine the ultrastructural relationships of cholesterol crystals and apatite deposits in human atherosclerotic lesions. Segments of human aortic atherosclerotic lesions were obtained at autopsy, fixed in glutaraldehyde and dehydrated without using any organic solvents. The aortic segments were coated with carbon and subjected to various scanning electron microscope analyses. These included secondary electron imaging, back scattering of primary electrons, energy dispersive X-ray analysis of selected spots followed by area mapping of calcium and phosphorus, and cathodoluminescence. The information gathered from scanning of selected areas in the lesions by all the techniques showed that cholesterol crystals and apatite deposits are close to each other, within 10 mum distance or less. Cholesterol crystals are often surrounded by or adjacent to apatite. The results indicate that cholesterol and apatite crystals form closely linked agglomerates in human atherosclerotic lesions. Further studies are needed to determine whether precipitation of calcium and cholesterol are somehow linked during atherosclerotic lesion development. C1 NHLBI,EXPTL ATHEROSCLEROSIS SECT,BLDG 10,ROOM 5N-113,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,GRAD SCH APPL SCI & TECHNOL,CASALI INST APPL CHEM,IL-91904 JERUSALEM,ISRAEL. HADASSAH UNIV HOSP,DEPT CARDIOL,IL-91120 JERUSALEM,ISRAEL. NR 16 TC 2 Z9 2 U1 0 U2 0 PU SCANNING MICROSCOPY INT PI CHICAGO PA PO BOX 66507, AMF O'HARE, CHICAGO, IL 60666 SN 1051-6794 J9 CELL MATER JI Cells Mat. PY 1992 VL 2 IS 4 BP 339 EP 346 PG 8 WC Cell Biology; Medicine, Research & Experimental; Materials Science, Biomaterials SC Cell Biology; Research & Experimental Medicine; Materials Science GA KP120 UT WOS:A1992KP12000007 ER PT B AU BURBELO, P GABRIEL, G WUJECK, J KEDAR, VV WEEKS, BS KLEINMAN, HK YAMADA, Y AF BURBELO, P GABRIEL, G WUJECK, J KEDAR, VV WEEKS, BS KLEINMAN, HK YAMADA, Y BE CLEMENT, B GUILLOUZO, A TI BASEMENT-MEMBRANE GENES AND TRANSCRIPTION FACTORS SO CELLULAR AND MOLECULAR ASPECTS OF CIRRHOSIS SE COLLOQUE INSERM LA English DT Proceedings Paper CT INTERNATIONAL CONF ON CELLULAR AND MOLECULAR BASES OF LIVER CIRRHOSIS CY JUL 03-04, 1991 CL RENNES, FRANCE SP INSERM RP BURBELO, P (reprint author), NIDR,DEV BIOL LAB,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INSERM / JOHN LIBBEY EUROTEXT PI PARIS PA PARIS BN 0-86196-342-3 J9 COLLOQ INSE PY 1992 VL 216 BP 135 EP 145 PG 11 WC Biochemistry & Molecular Biology; Urology & Nephrology SC Biochemistry & Molecular Biology; Urology & Nephrology GA BV65F UT WOS:A1992BV65F00014 ER PT B AU THORGEIRSSON, SS HUGGETT, AC BISGAARD, HC AF THORGEIRSSON, SS HUGGETT, AC BISGAARD, HC BE CLEMENT, B GUILLOUZO, A TI PHENOTYPIC CHARACTERISTICS AND NEOPLASTIC TRANSFORMATION OF PRIMITIVE EPITHELIAL-CELLS DERIVED FROM RAT-LIVER AND PANCREAS SO CELLULAR AND MOLECULAR ASPECTS OF CIRRHOSIS SE COLLOQUE INSERM LA English DT Proceedings Paper CT INTERNATIONAL CONF ON CELLULAR AND MOLECULAR BASES OF LIVER CIRRHOSIS CY JUL 03-04, 1991 CL RENNES, FRANCE SP INSERM RP THORGEIRSSON, SS (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INSERM / JOHN LIBBEY EUROTEXT PI PARIS PA PARIS BN 0-86196-342-3 J9 COLLOQ INSE PY 1992 VL 216 BP 287 EP 298 PG 12 WC Biochemistry & Molecular Biology; Urology & Nephrology SC Biochemistry & Molecular Biology; Urology & Nephrology GA BV65F UT WOS:A1992BV65F00031 ER PT J AU SINGH, VK KALRA, HK YAMAKI, K SHINOHARA, T AF SINGH, VK KALRA, HK YAMAKI, K SHINOHARA, T TI SUPPRESSION OF EXPERIMENTAL AUTOIMMUNE UVEITIS IN RATS BY THE ORAL-ADMINISTRATION OF THE UVEITOPATHOGENIC S-ANTIGEN FRAGMENT OR A CROSS-REACTIVE HOMOLOGOUS PEPTIDE SO CELLULAR IMMUNOLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; PEYERS PATCHES; IMMUNE-RESPONSES; IMMUNOLOGICAL SUPPRESSION; MOLECULAR MIMICRY; ADOPTIVE TRANSFER; SEQUENCE-ANALYSIS; INDUCED TOLERANCE; ALPHA-TRANSDUCIN; BOVINE RETINA C1 NEI,MOLEC BIOL SECT,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. OI Shinohara, Toshimichi/0000-0002-7197-9039 NR 49 TC 42 Z9 42 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD JAN PY 1992 VL 139 IS 1 BP 81 EP 90 DI 10.1016/0008-8749(92)90101-T PG 10 WC Cell Biology; Immunology SC Cell Biology; Immunology GA GW213 UT WOS:A1992GW21300007 PM 1728971 ER PT J AU HONNOR, RC NAGHSHINEH, S CUSHMAN, SW WOLFF, J SIMPSON, IA LONDOS, C AF HONNOR, RC NAGHSHINEH, S CUSHMAN, SW WOLFF, J SIMPSON, IA LONDOS, C TI CHOLERA AND PERTUSSIS TOXINS MODIFY REGULATION OF GLUCOSE-TRANSPORT ACTIVITY IN RAT ADIPOSE-CELLS - EVIDENCE FOR MEDIATION OF A CAMP-INDEPENDENT PROCESS BY G-PROTEINS SO CELLULAR SIGNALLING LA English DT Article DE ADIPOCYTES; GLUCOSE TRANSPORT; CHOLERA TOXIN; PERTUSSIS TOXIN; G-PROTEIN ID ISLET-ACTIVATING PROTEIN; ADENYLATE-CYCLASE; INSULIN-RECEPTORS; BINDING PROTEINS; FAT-CELL; ADIPOCYTES; ADENOSINE; PHOSPHORYLATION; INHIBITION; LIPOLYSIS AB Adenylyl cyclase in rat adipose cells is stimulated by ligands for R(s) receptors (e.g. isoproterenol) and inhibited by ligands for R(i) receptors (e.g. adenosine). In contrast, R(s) receptors mediate inhibition and R(i) receptors mediate augmentation of insulin-stimulated glucose transport activity by a process independent of changes in cellular cAMP-dependent protein kinase activity [Kuroda M., Honnor R. C., Cushman S. W., Londos C. and Simpson I. A. (1987) J. biol. Chem. 262, 245-253]. The present study examines the possible role of G-proteins in the regulation of insulin-stimulated glucose transport activity by R(s) and R(i) receptors. First, conditions were established that permit intoxication of isolated rat adipocytes by cholera and pertussis toxins without compromising cell integrity. Effectiveness of toxin treatment was monitored by examining adenylyl cyclase activity in isolated plasma membranes. Secondly, neither toxin interfered with the ability of a maximal concentration insulin to initiate the glucose transport response. Thirdly, pertussis toxin eliminated the augmenting effects of adenosine on insulin-stimulated glucose transport activity, but enhanced the inhibitory effects of isoproterenol. Findings with ligands for other R(i) receptors (nicotinic acid and prostaglandin E2) mirrored those with adenosine. Finally, cholera toxin elicted a modest depression of transport activity, and only in the absence of an R(i) ligand (e.g. adenosine). Furthermore, in contrast to the enhanced stimulation of adenylyl cyclase by isoproterenol and GTP, cholera toxin eliminated the inhibitory effect of isoproterenol on transport activity. The augmentative effects of adenosine on transport activity were unchanged. Measurements of (-/+ cAMP) cAMP-dependent protein kinase activity ratios reinforce the notion that modulation of glucose transport activity is independent of changes in cAMP. We conclude that regulation of glucose transport activity by R(s) and R(i) receptors is mediated by the G-proteins, G(s) and G(i) (or other toxin substrates), respectively. Inasmuch as such regulation occurs at the plasma membrane and appears to be cAMP-independent, it is suggested that glucose transporters may be direct targets for receptor: G-protein interactions. C1 NIDDKD,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892. NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. NIDDKD,CLIN ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 47 TC 17 Z9 17 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 JAN PY 1992 VL 4 IS 1 BP 87 EP 98 DI 10.1016/0898-6568(92)90010-6 PG 12 WC Cell Biology SC Cell Biology GA HJ456 UT WOS:A1992HJ45600008 PM 1315147 ER PT J AU SHEARER, GM CLERICI, M AF SHEARER, GM CLERICI, M TI T-HELPER CELL IMMUNE DYSFUNCTION IN ASYMPTOMATIC, HIV-1-SEROPOSITIVE INDIVIDUALS - THE ROLE OF TH1-TH2 CROSS-REGULATION SO CHEMICAL IMMUNOLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS-RELATED COMPLEX; DEFICIENCY SYNDROME AIDS; PNEUMOCYSTIS-CARINII PNEUMONIA; HIV-SEROPOSITIVE INDIVIDUALS; MIXED LYMPHOCYTE-REACTION; POLYMERASE CHAIN-REACTION; HUMAN PERIPHERAL-BLOOD; RETROVIRUSES HTLV-III; STATES-AIR-FORCE RP SHEARER, GM (reprint author), NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892, USA. NR 116 TC 64 Z9 64 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-0145 J9 CHEM IMMUNOL JI Chem. Immunol. PY 1992 VL 54 BP 21 EP 43 PG 23 WC Immunology SC Immunology GA JQ838 UT WOS:A1992JQ83800002 PM 1418612 ER PT J AU HORGAN, KJ TANAKA, Y SHAW, S AF HORGAN, KJ TANAKA, Y SHAW, S TI POSTTHYMIC DIFFERENTIATION OF CD4 LYMPHOCYTES-T - NAIVE VERSUS MEMORY SUBSETS AND FURTHER SPECIALIZATION AMONG MEMORY CELLS SO CHEMICAL IMMUNOLOGY LA English DT Review ID LEUKOCYTE-COMMON ANTIGEN; INTERFERON-GAMMA PRODUCTION; SUPPRESSOR-INDUCER PHENOTYPES; SYSTEMIC LUPUS-ERYTHEMATOSUS; POST-THYMIC DIFFERENTIATION; HELPER-INDUCER; PERIPHERAL-BLOOD; IMMUNODEFICIENCY-VIRUS; MONOCLONAL-ANTIBODY; ADHESION MOLECULES C1 NCI,EXPTL IMMUNOL BRANCH,NIH BLDG 10,ROOM 4B17,BETHESDA,MD 20892. NR 155 TC 17 Z9 17 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-0145 J9 CHEM IMMUNOL JI Chem. Immunol. PY 1992 VL 54 BP 72 EP 102 PG 31 WC Immunology SC Immunology GA JQ838 UT WOS:A1992JQ83800005 PM 1358112 ER PT J AU KING, CL NUTMAN, TB AF KING, CL NUTMAN, TB TI BIOLOGICAL ROLE OF HELPER T-CELL SUBSETS IN HELMINTH INFECTIONS SO CHEMICAL IMMUNOLOGY LA English DT Review ID HUMAN IGE SYNTHESIS; IDIOPATHIC HYPEREOSINOPHILIC SYNDROME; RECOMBINANT HUMAN INTERLEUKINS; SCHISTOSOMA-MANSONI INFECTION; HUMAN LYMPHATIC FILARIASIS; CD4+ LYMPHOCYTES-T; HUMAN-BONE MARROW; HOUSE DUST MITE; INTERFERON-GAMMA; PROTECTIVE IMMUNITY C1 NIH,PARASIT DIS LAB,BETHESDA,MD 20892. RP KING, CL (reprint author), CASE WESTERN RESERVE UNIV,DIV GEOG MED,2109 ADELBERT RD,CLEVELAND,OH 44106, USA. NR 119 TC 33 Z9 34 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-0145 J9 CHEM IMMUNOL JI Chem. Immunol. PY 1992 VL 54 BP 136 EP 165 PG 30 WC Immunology SC Immunology GA JQ838 UT WOS:A1992JQ83800008 PM 1358109 ER PT J AU MATSUSHIMA, K BALDWIN, ET MUKAIDA, N AF MATSUSHIMA, K BALDWIN, ET MUKAIDA, N TI INTERLEUKIN-8 AND MCAF - NOVEL LEUKOCYTE RECRUITMENT AND ACTIVATING CYTOKINES SO CHEMICAL IMMUNOLOGY LA English DT Review ID NEUTROPHIL CHEMOTACTIC FACTOR; TUMOR-NECROSIS-FACTOR; MONOCYTE CHEMOATTRACTANT PROTEIN-1; BLOOD MONONUCLEAR LEUKOCYTES; GROWTH STIMULATORY ACTIVITY; NF-KAPPA-B; ACUTE-PHASE RESPONSE; AMINO-ACID-SEQUENCE; DNA-BINDING SUBUNIT; ENDOTHELIAL-CELLS C1 ABL BASIC RES PROGRAM,CTR DEV,FREDERICK,MD. KANAZAWA UNIV,CANC RES INST,DEPT PHARMACOL,KANAZAWA,ISHIKAWA 920,JAPAN. NCI,FREDERICK CANC RES FACIL,CRYSTALLOG LAB,FREDERICK,MD 21701. RP MATSUSHIMA, K (reprint author), NCI,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,MOLEC IMMUNOREGULAT LAB,BLDG 560,FREDERICK,MD 21702, USA. RI Mukaida, Naofumi/D-7623-2011 OI Mukaida, Naofumi/0000-0002-4193-1851 NR 97 TC 159 Z9 166 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-0145 J9 CHEM IMMUNOL JI Chem. Immunol. PY 1992 VL 51 BP 236 EP 265 PG 30 WC Immunology SC Immunology GA HD758 UT WOS:A1992HD75800009 PM 1567543 ER PT J AU KOVACIK, V WHITTAKER, NF KOVAC, P AF KOVACIK, V WHITTAKER, NF KOVAC, P TI SEQUENTIAL-ANALYSIS OF OLIGOSACCHARIDES BY DIRECT CHEMICAL IONIZATION MASS-SPECTROMETRY SO CHEMICAL PAPERS-CHEMICKE ZVESTI LA English DT Article ID COLLISIONAL ACTIVATION SPECTRA; METHYL BETA-GLYCOSIDES; ION KINETIC-ENERGY AB Homo- and heterooligosaccharides, composed of hexopyranose, deoxyhexopyranose, and acetamidohexose units, have been examined by direct chemical ionization (DCI) mass spectrometry. Their DCI scan, using ammonia as the reaction gas, gives rise to structurally significant ions. The information thus obtained aids significantly in the sequential analysis of the di- and trisaccharides without derivatization. C1 NIDDK,BETHESDA,MD 20892. RP KOVACIK, V (reprint author), SLOVAK ACAD SCI,INST CHEM,CS-84238 BRATISLAVA,CZECHOSLOVAKIA. NR 12 TC 0 Z9 0 U1 0 U2 1 PU SLOVAK ACADEMIC PRESS LTD PI BRATISLAVA PA PO BOX 57, NAM SLOBODY 6, 810 05 BRATISLAVA, SLOVAKIA SN 0366-6352 J9 CHEM PAP-CHEM ZVESTI JI Chem. Pap.-Chem. Zvesti PY 1992 VL 46 IS 6 BP 410 EP 412 PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA KU777 UT WOS:A1992KU77700013 ER PT J AU RETTIE, AE KORZEKWA, KR KUNZE, KL LAWRENCE, RF EDDY, AC AOYAMA, T GELBOIN, HV GONZALEZ, FJ TRAGER, WF AF RETTIE, AE KORZEKWA, KR KUNZE, KL LAWRENCE, RF EDDY, AC AOYAMA, T GELBOIN, HV GONZALEZ, FJ TRAGER, WF TI HYDROXYLATION OF WARFARIN BY HUMAN CDNA-EXPRESSED CYTOCHROME-P-450 - A ROLE FOR P-4502C9 IN THE ETIOLOGY OF (S)-WARFARIN DRUG-INTERACTIONS SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID HUMAN-LIVER-MICROSOMES; GENE SUBFAMILY; TOLBUTAMIDE; INHIBITION; PURIFICATION; ACTIVATION; METABOLISM; ISOZYMES; ENZYME AB Previous kinetic studies have identified a high-affinity (S)-warfarin 7-hydroxylase present in human liver microsomes which appears to be responsible for the termination of warfarin's biological activity. Inhibition of the formation of (S)-7-hydroxywarfarin, the inactive, major metabolite of racemic warfarin in humans, is known to be the cause of several of the drug interactions experienced clinically upon coadministration of warfarin with other therapeutic agents. In order to identify the specific form(s) of human liver cytochrome P-450 involved in this particular toxicity, we have determined the metabolic profiles of 11 human cytochrome P-450 forms expressed in HepG2 cells toward both (R)- and (S)-warfarin. Of the 11 forms examined only 2C9 displayed the regioselectivity and stereoselectivity appropriate for the high-affinity human liver microsomal (S)-7-hydroxylase. We further compared Michaelis-Menten and sulfaphenazole inhibition constants for (S)-warfarin 7-hydroxylation catalyzed by cDNA-expressed 2C9 and by human liver microsomes. Similar kinetic constants were obtained for each enzyme source. It is concluded that 2C9 is likely to be a principal form of human liver P-450 which modulates the in vivo anticoagulant activity of the drug. It is further concluded that those drug interactions with warfarin that arise as a result of decreased clearance of the biologically more potent S-enantiomer may have as their common basis the inhibition of P-450 2C9. C1 UNIV WASHINGTON,SCH PHARM,DEPT MED CHEM,SEATTLE,WA 98195. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. UNIV WASHINGTON,SCH MED,DEPT SURG,SEATTLE,WA 98195. FU NIGMS NIH HHS [GM 32165] NR 31 TC 489 Z9 498 U1 2 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JAN-FEB PY 1992 VL 5 IS 1 BP 54 EP 59 DI 10.1021/tx00025a009 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA HB644 UT WOS:A1992HB64400010 PM 1581537 ER PT J AU HANNA, PM KADIISKA, MB MASON, RP AF HANNA, PM KADIISKA, MB MASON, RP TI OXYGEN-DERIVED FREE-RADICAL AND ACTIVE OXYGEN COMPLEX-FORMATION FROM COBALT(II) CHELATES INVITRO SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID COBALTOUS CHLORIDE; HYDROGEN-PEROXIDE; SINGLET OXYGEN; HYDROXYL; IRON; SUPEROXIDE; ION; ACTIVATION; NITROXIDE; SALTS AB The electron paramagnetic resonance (EPR) spin trapping technique was used to study the generation of oxygen free radicals from the reaction of hydrogen peroxide with various Co(II) complexes in pH 7.4 phosphate buffer. The 5,5-dimethyl-1-pyrroline N-oxide (DMPO) spin trap was used in these experiments to detect superoxide and hydroxyl free radicals. Superoxide radical was generated from the reaction of H2O2 with Co(II), but was inhibited when Co(II) was chelated with adenosine 5'-diphosphate or citrate. Visible absorbance spectra revealed no change in the final oxidation state of the cobalt ion in these samples. The EDTA complex also prevented detectable free-radical formation when H2O2 was added, but visible absorbance data indicated oxidation of the Co(II) to Co(III) in this case. The amount of DMPO/*OOH adduct detected by EPR was greatly enhanced when H2O2 reacted with the nitrilotriacetate complex relative to Co(II) alone, and in addition, concurrent formation of the DMPO/*OH adduct due to slow oxidation of Co(II) was observed. The hydroxyl radical adduct formation was suppressed by ethanol, but not DMSO, indicating that free hydroxyl radical was not formed. The deferoxamine nitroxide radical was exclusively formed when H2O2 was added to the Co(II) complex of this ligand, most probably in a site-specific manner. In the presence of ethylenediamine, Co(II) bound molecular O2 and directly oxidized DMPO to its DMPO/*OH adduct without first forming free superoxide, hydroxyl radical, or hydrogen peroxide. An experiment using O-17-enriched water revealed that the Co(II)-ethylenediamine complex caused the DMPO to react with solvent water to form the DMPO/*OH adduct. The relevance of these results to toxicological studies of cobalt is discussed. C1 BULGARIAN ACAD SCI,INST PHYSIOL,BU-1113 SOFIA,BULGARIA. RP HANNA, PM (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 35 TC 54 Z9 54 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JAN-FEB PY 1992 VL 5 IS 1 BP 109 EP 115 DI 10.1021/tx00025a019 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA HB644 UT WOS:A1992HB64400020 PM 1316186 ER PT J AU COLE, PM WOOLGER, C POWER, TG SMITH, KD AF COLE, PM WOOLGER, C POWER, TG SMITH, KD TI PARENTING DIFFICULTIES AMONG ADULT SURVIVORS OF FATHER DAUGHTER INCEST SO CHILD ABUSE & NEGLECT LA English DT Article DE INCEST; PARENTING; ADULT SURVIVORS; SELF-REPORTING ID CHILDREN AB Women with a history of father-daughter incest as children often report difficulty in parenting their own children. This study examined the self-reported parenting experience and practices of women who were incest victims as children. Since many incest victims are also children of alcoholics, we compared their reports of parenting with those of women whose fathers were alcoholic but not sexually abusive, and to women who had no known risk during their childhood. The findings were that incest survivors reported significantly less confidence and less sense of control as parents than nonrisk mothers. In addition, they reported significantly less support in the parental partnership with their spouses, and reported being less consistent and organized, and making fewer maturity demands on their children. The findings are discussed in terms of the incest survivor's sense of inefficacy and loss of control, the potential of the marital relationship to buffer the adverse effects of growing up in the dysfunctional, incestuous family, and future research directions. C1 UNIV HOUSTON,HOUSTON,TX 77004. RP COLE, PM (reprint author), NIMH,DEV PSYCHOL LAB,BLDG 15K,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 22 TC 64 Z9 64 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0145-2134 J9 CHILD ABUSE NEGLECT JI Child Abuse Negl. PY 1992 VL 16 IS 2 BP 239 EP 249 DI 10.1016/0145-2134(92)90031-L PG 11 WC Family Studies; Psychology, Social; Social Work SC Family Studies; Psychology; Social Work GA HL515 UT WOS:A1992HL51500008 PM 1559172 ER PT J AU LAMB, ME STERNBERG, KJ AF LAMB, ME STERNBERG, KJ TI ESTABLISHING THE DESIGN SO CHILDREN AND YOUTH SERVICES REVIEW LA English DT Article AB Careful evaluation is a prerequisite for progress in developing effective programs for children. In this regard, objective empirical information is central to understanding the effectiveness of family preservation programs. In this article four issues that need to be considered when evaluating family preservation programs are considered. First, there is a need to specify goals of the intervention in advance. Second, evaluation strategies need to consider the difference between treatment and effects. Third, it is important to examine the design considerations that effect the credibility of the evaluation. Finally, the article provides suggestions for measures that could be used in multisite interventions. RP LAMB, ME (reprint author), NICHHD,SOCIAL & EMOT DEV SECT,9190 ROCKVILLE PIKE,RM 331,BETHESDA,MD 20814, USA. NR 15 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0190-7409 J9 CHILD YOUTH SERV REV JI Child. Youth Serv. Rev. PY 1992 VL 14 IS 1-2 BP 157 EP 165 DI 10.1016/0190-7409(92)90021-M PG 9 WC Family Studies; Social Work SC Family Studies; Social Work GA HQ027 UT WOS:A1992HQ02700013 ER PT J AU MORRISON, A SUGINO, A AF MORRISON, A SUGINO, A TI ROLES OF POL3, POL2 AND PMS1 GENES IN MAINTAINING ACCURATE DNA-REPLICATION SO CHROMOSOMA LA English DT Article ID 5' EXONUCLEASE ACTIVITY; SACCHAROMYCES-CEREVISIAE; POLYMERASE-ALPHA; NUCLEAR EXTRACTS; MISMATCH REPAIR; SEQUENCE; CELLS; SUBUNIT; SITE C1 NIEHS,MOLEC GENET LAB,POB 12233,RES TRIANGLE PK,NC 27709. OSAKA UNIV,DEPT MOLEC IMMUNOL,MICROBIAL DIS RES INST,SUITA,OSAKA 565,JAPAN. NR 23 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0009-5915 J9 CHROMOSOMA JI Chromosoma PY 1992 VL 102 IS 1 SU S BP S147 EP S149 DI 10.1007/BF02451799 PG 3 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA KF854 UT WOS:A1992KF85400021 PM 1291235 ER PT J AU WOUDE, V HUNT HUNTER DOREE KIRSCHNER SHALLOWAY NASMYTH BEACH CROSS NIGG AF WOUDE, V HUNT HUNTER DOREE KIRSCHNER SHALLOWAY NASMYTH BEACH CROSS NIGG TI THE ROLE OF MOS IN MEIOTIC MATURATION SO CIBA FOUNDATION SYMPOSIA LA English DT Discussion ID XENOPUS OOCYTES; PROTO-ONCOGENE; PRODUCT; PROTOONCOGENE; EGGS C1 IMPERIAL CANC RES FUND,S MIMMS EN6 3LD,ENGLAND. SALK INST,MOLEC BIOL & VIROL LAB,SAN DIEGO,CA 92186. BIOCHEM CRBM,CNRS,F-34033 MONTPELLIER 1,FRANCE. UNIV CALIF SAN FRANCISCO,SCH MED,DEPT BIOCHEM & BIOPHYS,SAN FRANCISCO,CA 94143. CORNELL UNIV,BIOCHEM MOLEC & CELL BIOL SECT,ITHACA,NY 14853. RES INST MOLEC PATHOL,A-1030 VIENNA,AUSTRIA. COLD SPRING HARBOR LAB,COLD SPRING HARBOR,NY 11724. ROCKEFELLER UNIV,NEW YORK,NY 10021. SWISS INST EXPTL CANC RES,CH-1066 EPALINGES,SWITZERLAND. RP WOUDE, V (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,POB B,FREDERICK,MD 21702, USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0300-5208 J9 CIBA F SYMP JI CIBA Found. Symp. PY 1992 VL 170 BP 244 EP 247 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA JQ182 UT WOS:A1992JQ18200016 ER PT J AU MELLON, PL WETSEL, WC WINDLE, JJ VALENCA, MM GOLDSMITH, PC WHYTE, DB ERALY, SA NEGROVILAR, A WEINER, RI AF MELLON, PL WETSEL, WC WINDLE, JJ VALENCA, MM GOLDSMITH, PC WHYTE, DB ERALY, SA NEGROVILAR, A WEINER, RI TI IMMORTALIZED HYPOTHALAMIC GONADOTROPIN-RELEASING-HORMONE NEURONS SO CIBA FOUNDATION SYMPOSIA LA English DT Article ID FIBRILLARY ACIDIC PROTEIN; TRANSGENIC MICE; T-ANTIGEN; CELL-LINES; MORPHOLOGICAL CHARACTERIZATION; HYPOGONADAL MOUSE; NERVOUS-SYSTEM; GENE-THERAPY; RAT; EXPRESSION AB The neuroendocrine hypothalamus has been intensively studied using whole animals and tissue slices. However, it has been difficult to approach questions at the molecular and cellular level. By targeting expression of the oncogene product, simian virus 40 T antigen, in transgenic mice using the regulatory domain of the rat gonadotropin-releasing hormone (GnRH) gene, we have produced specific hypothalamic tumours. These tumours have been cultured to produce clonal cell lines (GT-I cells) that express T antigen, GnRH and many other neuronal markers, but do not express other hypothalamic hormones. These immortal cell lines have a distinctive neuronal phenotype, process the GnRH peptide accurately and secrete GnRH in a pulsatile pattern. Thus, by targeting oncogenesis to a defined population of neurons using the regulatory region of a gene that is expressed late in differentiation of that cell lineage, we have succeeded in immortalizing hypothalamic GnRH neurons. The GT-1 cell lines are an excellent model for future molecular, cell biological, physiological and biochemical investigations into the mechanisms involved in regulation of GnRH and the characteristics of an isolated central nervous system neuron. Their derivation demonstrates the utility of targeting tumorigenesis to specific differentiated neurons of the central nervous system in transgenic mice. C1 SALK INST,SAN DIEGO,CA 92186. UNIV CALIF SAN DIEGO,SCH MED,SAN DIEGO,CA 92186. NIEHS,MOLEC & INTEGRAT NEUROSCI,RES TRIANGLE PK,NC 27709. UNIV CALIF SAN FRANCISCO,CTR REPROD ENDOCRINOL,SAN FRANCISCO,CA 94143. RI Valenca, Marcelo/A-4302-2013 OI Valenca, Marcelo/0000-0003-0678-3782 FU NICHD NIH HHS [HD 08924, HD 20377]; NIDDK NIH HHS [DK 44838, R01 DK044838] NR 41 TC 26 Z9 26 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0300-5208 J9 CIBA F SYMP JI CIBA Found. Symp. PY 1992 VL 168 BP 104 EP 126 PG 23 WC Medicine, General & Internal SC General & Internal Medicine GA JJ004 UT WOS:A1992JJ00400007 PM 1330456 ER PT J AU YOUNG, WS AF YOUNG, WS TI REGULATION OF GENE-EXPRESSION IN THE HYPOTHALAMUS - HYBRIDIZATION HISTOCHEMICAL-STUDIES SO CIBA FOUNDATION SYMPOSIA LA English DT Article ID CORTICOTROPIN-RELEASING FACTOR; VASOPRESSIN MESSENGER-RNA; RAT SUPRACHIASMATIC NUCLEUS; THYROID-HORMONE REGULATION; CELL-SPECIFIC EXPRESSION; NEURO-ENDOCRINE NEURONS; PARAVENTRICULAR NUCLEUS; INSITU HYBRIDIZATION; RIBONUCLEIC-ACID; MAGNOCELLULAR NEURONS AB Hybridization histochemistry has bridged molecular biology and neuroanatomy to provide nearly dynamic views of gene expression in the brain-perhaps especially in the hypothalamus. These snapshots of transcript levels with precise anatomical localization have revealed new insights into gene regulation in the hypothalamus under specific conditions. Magnocellular neurons in the paraventricular and supraoptic nuclei produce vasopressin and oxytocin. Transcript levels for these hormones are affected by hyperosmolality, as are those for many other neuropeptides. Patterns of gene expression in the magnocellular neurons in these nuclei during development and under different physiological conditions have been studied less extensively. The parvocellular neurons of the paraventricular nucleus produce corticotropin-releasing factor and thyrotropin-releasing hormone. Expression of the corticotropin-releasing factor gene is regulated by glucocorticoids. Physiological stresses, which activate the hypothalamo-pituitary-adrenal axis, also affect gene expression in the parvocellular paraventricular nucleus. Thyrotropin-releasing hormone is synthesized in a different set of parvocellular neurons in the paraventricular nucleus and in other neurons of the hypothalamus. Expression of the thyrotropin-releasing hormone gene is regulated by thyroid hormone. The suprachiasmatic nucleus contains neurons that produce vasopressin or vasoactive intestinal polypetide in a circadian rhythm. Future studies using combinations of classical neuroanatomical techniques, hybridization histochemistry and immunohistochemistry will further our understanding of hypothalamic responses to various stimuli. RP YOUNG, WS (reprint author), NATL INST MENT HLTH,CELL BIOL LAB,BETHESDA,MD 20892, USA. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 NR 89 TC 9 Z9 10 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0300-5208 J9 CIBA F SYMP JI CIBA Found. Symp. PY 1992 VL 168 BP 127 EP 143 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA JJ004 UT WOS:A1992JJ00400008 PM 1425021 ER PT J AU KUHAR, MJ AF KUHAR, MJ TI MOLECULAR PHARMACOLOGY OF COCAINE - A DOPAMINE HYPOTHESIS AND ITS IMPLICATIONS SO CIBA FOUNDATION SYMPOSIA LA English DT Article ID RAT STRIATUM; UPTAKE SITES; INTRAVENOUS COCAINE; NONHUMAN-PRIMATES; LIGAND-BINDING; RECEPTORS; SEROTONIN; DRUGS; TRANSPORTERS; INHIBITION AB The reinforcing properties of cocaine have been related to cocaine binding at the dopamine transporter in mesolimbocortical neurons. The molecular properties of the transporter have been studied in a number of laboratories. While this 'dopamine hypothesis' is strongly supported in animal studies of drug self-administration, the extent of its involvement in human drug dependence has not been fully elucidated. RP KUHAR, MJ (reprint author), NIDA,ADDICT RES CTR,NEUROSCI BRANCH,POB 5180,BALTIMORE,MD 21224, USA. NR 40 TC 45 Z9 45 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0300-5208 J9 CIBA F SYMP JI CIBA Found. Symp. PY 1992 VL 166 BP 81 EP 95 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA HV055 UT WOS:A1992HV05500006 PM 1638923 ER PT J AU AKAIKE, N TANAKA, C MIKOSHIBA, K TSIEN, RW NISHIZUKA, Y DALY, JW FREDHOLM, B AF AKAIKE, N TANAKA, C MIKOSHIBA, K TSIEN, RW NISHIZUKA, Y DALY, JW FREDHOLM, B TI GENERAL DISCUSSION-1 - THE METABOTROPIC GLUTAMATE RECEPTOR SO CIBA FOUNDATION SYMPOSIA LA English DT Discussion ID PROTEIN KINASE-C; CYCLIC-AMP ACCUMULATION; CELL LEUKEMIA LINE; RAT-BRAIN SLICES; IMMUNOCYTOCHEMICAL LOCALIZATION; CEREBRAL-CORTEX; INOSITOL PHOSPHATES; CAMP FORMATION; NCB-20 CELLS; T-CELLS C1 KOBE UNIV, SCH MED, DEPT PHARMACOL, KOBE 650, JAPAN. OSAKA UNIV, INST PROT RES, SUITA, OSAKA 565, JAPAN. STANFORD UNIV, MED CTR, ARNOLD & MABEL BECKMAN CTR, DEPT MOLEC & CELLULAR PHYSIOL, STANFORD, CA 94305 USA. KOBE UNIV, SCH MED, DEPT BIOCHEM, KOBE 650, JAPAN. NIDDK, BIOORGAN CHEM LAB, BETHESDA, MD 20892 USA. KAROLINSKA INST, DEPT PHARMACOL, S-10401 STOCKHOLM 60, SWEDEN. RP TOHOKU UNIV, SCH MED, DEPT NEUROPHYSIOL, 1-1 SEIRYO MACHI, AOBA KU, SENDAI, MIYAGI 980, JAPAN. RI Mikoshiba, Katsuhiko/N-7943-2015 NR 34 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0300-5208 J9 CIBA F SYMP JI CIBA Found. Symp. PY 1992 VL 164 BP 197 EP + PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA HP429 UT WOS:A1992HP42900014 ER PT J AU MARON, BJ FANANAPAZIR, L AF MARON, BJ FANANAPAZIR, L TI SUDDEN CARDIAC DEATH IN HYPERTROPHIC CARDIOMYOPATHY SO CIRCULATION LA English DT Article; Proceedings Paper CT SYMP ON CURRENT PERSPECTIVES ON THE PROBLEM OF SUDDEN CARDIAC DEATH CY SEP 24-25, 1990 CL DALLAS, TX SP AMER HEART ASSOC DE HYPERTROPHIC CARDIOMYOPATHY; SUDDEN CARDIAC DEATH; RISK FACTORS ID LEFT-VENTRICULAR HYPERTROPHY; SUB-AORTIC STENOSIS; OBSTRUCTIVE CARDIOMYOPATHY; CLINICAL COURSE; HIGH-RISK; PROGNOSIS; SYNCOPE; EXTENT; ARREST; ARRHYTHMIA AB Sudden death is an important facet of the natural history of hypertrophic cardiomyopathy. Issues related to the nature and etiology of sudden death and the prospective identification of those patients at increased risk have been the subject of intense study, and consequently, our concepts and knowledge have continued to evolve. Occurrence of sudden death has been reported to be about 2-3% per year in a hospital-based referral population and, although described in most age groups, is most common in older children and young adults. The typical profile is that of a young asymptomatic patient with substantially increased left ventricular wall thickness who dies while performing sedentary or modest physical activities; however, a substantial minority die suddenly during or just after severe exertion, including those participating in competitive athletics. Other risk factors that have been identified in patients with hypertrophic cardiomyopathy include nonsustained ventricular tachycardia on ambulatory electrocardiogram, a strong family history of sudden death, and prior occurrence of syncope (or cardiac arrest). Electrophysiological studies have shown that most patients judged at increased risk for sudden death have sinoatrial or His-Purkinje conduction disease or inducible supraventricular or ventricular tachycardia; inducibility of a sustained ventricular arrhythmia is associated with prior occurrence of syncope or cardiac arrest. Hemodynamic and electrophysiological studies in patients with hypertrophic cardiomyopathy have demonstrated several potential mechanisms for cardiac arrest or sudden death, including atrial arrhythmias associated with hypotension, bradyarrhythmias, and ventricular tachyarrhythmias, all of which can be exacerbated in the presence of left ventricular outflow tract obstruction or myocardial ischemia. RP MARON, BJ (reprint author), NHLBI,BLDG 10,ROOM 7B15,BETHESDA,MD 20892, USA. NR 53 TC 65 Z9 66 U1 2 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN PY 1992 VL 85 IS 1 SU S BP 57 EP 63 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA HA414 UT WOS:A1992HA41400009 ER PT J AU REED, D REED, C STEMMERMANN, G HAYASHI, T AF REED, D REED, C STEMMERMANN, G HAYASHI, T TI ARE AORTIC-ANEURYSMS CAUSED BY ATHEROSCLEROSIS SO CIRCULATION LA English DT Article DE SMOKING; EPIDEMIOLOGY; BLOOD PRESSURE; CHOLESTEROL; ANEURYSMS; ATHEROSCLEROSIS ID CORONARY HEART-DISEASE; LIFESTYLE CHARACTERISTICS; PATHOGENESIS; DIETARY; PROGRAM AB Background. The emerging controversy concerning the causal role of atherosclerosis in the development of aortic aneurysms was examined using the accumulated clinical and autopsy data obtained during a 20-year follow-up of a cohort of more than 8,000 men of Japanese ancestry in Hawaii. Methods and Results. Analyses of 174 clinical incident events indicated that there were two types of aneurysmal disease, 151 aortic aneurysms and 23 aortic dissections. The baseline risk factors that predicted the clinical aortic aneurysms were the same factors that predicted aortic atherosclerosis in the same cohort, namely, high blood pressure, high serum cholesterol, and cigarette smoking. These same risk factors were also significantly associated with the occurrence of 27 aortic aneurysms among 293 autopsied men. The less common aortic dissections had an age-specific incidence pattern indicative of an innate susceptibility precipitated by an exposure to another factor. This pattern was consistent with the findings that the incidence of aortic dissections was predicted mainly by baseline high blood pressure. Conclusions. From the perspective of prevention, it appears that the risk factors for aortic atherosclerosis and probably atherosclerosis itself are necessary elements in the causal pathway for the great majority of aortic aneurysms in this cohort. C1 KAISER PERMANENTE MED CTR,SAN FRANCISCO,CA. KUAKINI MED CTR,JAPAN HAWAII CANC STUDY,HONOLULU,HI. NHLBI,BETHESDA,MD 20892. KUAKINI MED CTR,DEPT PATHOL,HONOLULU,HI. FU NHLBI NIH HHS [N01-HC-02901] NR 31 TC 208 Z9 211 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN PY 1992 VL 85 IS 1 BP 205 EP 211 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA GY582 UT WOS:A1992GY58200025 PM 1728451 ER PT J AU DOMANSKI, MJ ABELLA, G BAIM, D BRISTOW, JD CHARROW, R DETRE, K FELD, M FISHER, L FORRESTER, J GOLDBERG, S GRUNDFEST, WS HOLLOHAN, T HORAN, MJ JOHNSON, GC KENT, KM KING, SB SANBORN, JA SIMPSON, J TOPOL, E WATSON, JT AF DOMANSKI, MJ ABELLA, G BAIM, D BRISTOW, JD CHARROW, R DETRE, K FELD, M FISHER, L FORRESTER, J GOLDBERG, S GRUNDFEST, WS HOLLOHAN, T HORAN, MJ JOHNSON, GC KENT, KM KING, SB SANBORN, JA SIMPSON, J TOPOL, E WATSON, JT TI EVALUATION OF EMERGING TECHNOLOGIES FOR CORONARY REVASCULARIZATION SO CIRCULATION LA English DT Editorial Material DE EDITORIALS; CORONARY REVASCULARIZATION ID ANGIOPLASTY; MULTICENTER C1 UNIV FLORIDA,DIV CARDIOL,GAINESVILLE,FL 32611. BETH ISRAEL HOSP,DIV CARDIOL,BOSTON,MA 02215. OREGON HLTH SCI UNIV,DIV CARDIOL,PORTLAND,OR 97201. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,PITTSBURGH,PA 15260. MIT,REG LASER CTR,CAMBRIDGE,MA 02139. UNIV WASHINGTON,SEATTLE,WA 98195. CEDARS SINAI MED CTR,SURG,LOS ANGELES,CA 90048. THOMAS JEFFERSON UNIV,PHILADELPHIA,PA 19107. CEDARS SINAI MED CTR,LASER SURG & SURG RES,LOS ANGELES,CA 90048. US FDA,CTR DEVICES & RADIOL HLTH,OFF HLTH AFFAIRS,BETHESDA,MD 20014. WASHINGTON CARDIOL CTR,WASHINGTON,DC. EMORY UNIV HOSP,INTERVENT CARDIOL,ATLANTA,GA 30322. STANFORD UNIV HOSP,STANFORD,CA 94305. UNIV MICHIGAN,DIV CARDIOL,ANN ARBOR,MI 48109. RP DOMANSKI, MJ (reprint author), NHLBI,DIV HEART & VASC DIS,7550 WISCONSON AVE,BETHESDA,MD 20892, USA. NR 16 TC 3 Z9 3 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN PY 1992 VL 85 IS 1 BP 357 EP 361 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA GY582 UT WOS:A1992GY58200042 ER PT J AU VENTURA, C SPURGEON, H LAKATTA, EG GUARNIERI, C CAPOGROSSI, MC AF VENTURA, C SPURGEON, H LAKATTA, EG GUARNIERI, C CAPOGROSSI, MC TI KAPPA-OPIOID AND DELTA-OPIOID RECEPTOR STIMULATION AFFECTS CARDIAC MYOCYTE FUNCTION AND CA2+ RELEASE FROM AN INTRACELLULAR POOL IN MYOCYTES AND NEURONS SO CIRCULATION RESEARCH LA English DT Article DE OPIOID PEPTIDES; MYOCARDIAL CONTRACTION; CARDIAC MYOCYTES; NEURONS; CALCIUM; INOSITOL 1,4,5-TRISPHOSPHATE ID PERFUSED RAT-HEART; ACTION-POTENTIAL DURATION; GUINEA-PIG HEART; SARCOPLASMIC-RETICULUM; PROTEIN-KINASE; MESSENGER-RNA; POTASSIUM CONDUCTANCE; SYMPATHETIC-GANGLIA; MECHANICAL-ACTIVITY; ADENYLATE-CYCLASE AB We investigated the effects of mu, delta, and kappa opioid receptor stimulation on the contractile properties and cytosolic Ca2+ (Ca(i)) of adult rat left ventricular myocytes. Cells were field-stimulated at 1 Hz in 1.5 mM bathing Ca2+ at 23-degrees-C. The mu-agonist [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (10(-5) M) had no effect on the twitch. The delta-agonists methionine enkephalin and leucine enkephalin (10(-10) to 10(-6) M) and the kappa-agonist (trans-(dl)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclo-hexyl]-benzeneacetamide)methanesulfonate hydrate (U-50,488H; 10(-7) to 2 x 10(-5) M) had a concentration-dependent negative inotropic action. The sustained decrease in twitch amplitude due to U-50,488H was preceded by a transient increase in contraction. The effects of delta- and kappa-receptor stimulation were antagonized by naloxone and (-)-N-(3-furyl-methyl)-alpha-normetazocine methanesulfonate, respectively. In myocytes loaded with the Ca2+ probe indo-1, the effects of leucine enkephalin (10(-8) M) and U-50,488H (10(-5) M) on the twitch were associated with similar directional changes in the Ca(i) transient. Myofilament responsiveness to Ca2+ was assessed by the relation between twitch amplitude and systolic indo-1 transient. Leucine enkephalin (10(-8) M) had no effect, whereas U-50,488H (10(-5) M) increased myofilament responsiveness to Ca2+. We subsequently tested the hypothesis that delta and kappa opioid receptor stimulation may cause sarcoplasmic reticulum Ca2+ depletion. The sarcoplasmic reticulum Ca2+ content in myocytes and in a caffeine-sensitive intracellular Ca2+ store in neurons was probed in the absence of electrical stimulation via the rapid addition of a high concentration of caffeine from a patch pipette above the cell. U-50,488H and leucine enkephalin slowly increased Ca(i) or caused Ca(i) oscillations and eventually abolished the caffeine-triggered Ca(i) transient. These effects occurred in both myocytes and neuroblastoma-2a cells. In cardiac myocyte suspensions U-50,488H and leucine enkephalin both caused a rapid and sustained increase in inositol 1,4,5-trisphosphate. Thus, delta and kappa but not mu-opioids have a negative inotropic action due to a decreased Ca(i) transient. The decreased twitch amplitude due to kappa-receptor stimulation is preceded by a transient increase in contractility, and it occurs despite an enhanced myofilament responsiveness to Ca2+. The effects of delta and kappa-opioids appear coupled to phosphatidylinositol turnover and, at least in part, may be due to sarcoplasmic reticulum Ca2+ depletion. Ca2+ release and depletion of an intracellular store site occur in both myocytes and neurons and may represent a general mechanism for the effects of opioids. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224. UNIV BOLOGNA,DEPT BIOCHEM,I-40126 BOLOGNA,ITALY. NR 91 TC 169 Z9 184 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JAN PY 1992 VL 70 IS 1 BP 66 EP 81 PG 16 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA HE089 UT WOS:A1992HE08900008 PM 1309318 ER PT J AU LEVY, D MURABITO, JM ANDERSON, KM CHRISTIANSEN, JC CASTELLI, WP AF LEVY, D MURABITO, JM ANDERSON, KM CHRISTIANSEN, JC CASTELLI, WP TI ECHOCARDIOGRAPHIC LEFT-VENTRICULAR HYPERTROPHY - CLINICAL CHARACTERISTICS - THE FRAMINGHAM HEART-STUDY SO CLINICAL AND EXPERIMENTAL HYPERTENSION PART A-THEORY AND PRACTICE LA English DT Article; Proceedings Paper CT 2ND JOINT WHO/INTERNATIONAL-SOC-OF-HYPERTENSION SYMP ON THE PREVENTION OF HYPERTENSION AND CARDIOVASCULAR DISEASE CY JUN 01-03, 1991 CL CAMOGLIA, ITALY SP WHO, INT SOC HYPERTENS ID MYOCARDIAL-INFARCTION; MASS; ARRHYTHMIAS; POPULATION; DISEASE; PREVALENCE; MORTALITY; RISK; AGE AB Recent data suggest that echocardiographic left ventricular (LV) hypertrophy is associated with increased cardiovascular morbidity and mortality. Based upon application of sex-specific echocardiographic criteria for LV hypertrophy, the clinical characteristics of 863 subjects with and 4097 subjects without LV hypertrophy are examined. Subjects with LV hypertrophy are older, more obese, have higher blood pressure, and are more likely to have pre-existing coronary artery disease. In addition subjects with LV hypertrophy have a higher prevalence of reduced echocardiographic fractional shortening. We conclude that subjects with echocardiographic LV hypertrophy are at high risk for cardiovascular disease complications by virtue of their clinical profile. Additional investigation of the benefits of therapeutic interventions directed toward the prevention or regression of LV hypertrophy is warranted. C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. BOSTON UNIV,SCH MED,EPIDEMIOL & PREVENT MED SECT,BOSTON,MA 02118. BETH ISRAEL HOSP,DIV CARDIOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DIV CLIN EPIDEMIOL,BOSTON,MA 02115. RP LEVY, D (reprint author), FRAMINGHAM HEART DIS EPIDEMIOL STUDY,S THURBER ST,FRAMINGHAM,MA 01701, USA. NR 34 TC 20 Z9 22 U1 0 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0730-0077 J9 CLIN EXP HYPERTENS A PY 1992 VL 14 IS 1-2 BP 85 EP 97 DI 10.3109/10641969209036173 PG 13 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy; Physiology SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy; Physiology GA HA479 UT WOS:A1992HA47900008 PM 1531786 ER PT J AU LLOYD, A HICKIE, I HICKIE, C DWYER, J WAKEFIELD, D AF LLOYD, A HICKIE, I HICKIE, C DWYER, J WAKEFIELD, D TI CELL-MEDIATED-IMMUNITY IN PATIENTS WITH CHRONIC FATIGUE SYNDROME, HEALTHY CONTROL SUBJECTS AND PATIENTS WITH MAJOR DEPRESSION SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE FATIGUE; DEPRESSION; IMMUNITY; ANERGY ID IMMUNOLOGICAL ABNORMALITIES; INFECTIOUS MONONUCLEOSIS; LYMPHOCYTE FUNCTION; INTERFERON; DISORDER; ILLNESS; ADULTS AB The chronic fatigue syndrome (CFS) is characterized by severe persistent fatigue and neuropsychiatric symptoms. It has been proposed that the abnormalities in cell-mediated immunity which have been documented in patients with CFS may be attributable to a clinical depression, prevalent in patients with this disorder. Cell-mediated immune status was evaluated in patients with carefully defined CFS and compared with that of matched subjects with major depression (non-melancholic, non-psychotic) as well as healthy control subjects. Patients with CFS demonstrated impaired lymphocyte responses to phytohaemagglutinin (PHA) stimulation, and reduced or absent delayed-type hypersensitivity (DTH) skin responses when compared either with subjects with major depression or with healthy control subjects (P < 0.05 for each analysis). Although depression is common in patients with CFS, the disturbances of cell-mediated immunity in this disorder differ in prevalence and magnitude from, those associated with major depression. These observations strengthen the likelihood of a direct relationship between abnormal cell-mediated immunity and the etiology of CFS. C1 PRINCE HENRY HOSP,DIV MED,DEPT IMMUNOL,LITTLE BAY,NSW 2036,AUSTRALIA. PRINCE HENRY HOSP,DIV MED,DEPT INFECT DIS,LITTLE BAY,NSW 2036,AUSTRALIA. PRINCE HENRY HOSP,DIV PSYCHIAT,MOOD DISORDERS UNIT,LITTLE BAY,NSW 2036,AUSTRALIA. RP LLOYD, A (reprint author), NCI,MOLEC IMMUNOREGULAT LAB,BLDG 560,RM 31-19,FREDERICK,MD 21702, USA. NR 35 TC 73 Z9 74 U1 2 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD JAN PY 1992 VL 87 IS 1 BP 76 EP 79 PG 4 WC Immunology SC Immunology GA GY833 UT WOS:A1992GY83300013 PM 1733640 ER PT J AU ZWEIG, MH AF ZWEIG, MH TI INEFFICIENCY OF DIAGNOSTIC EFFICIENCY SO CLINICAL CHEMISTRY LA English DT Letter RP ZWEIG, MH (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,BETHESDA,MD 20892, USA. NR 5 TC 11 Z9 11 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 1992 VL 38 IS 1 BP 163 EP 164 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA HB646 UT WOS:A1992HB64600035 PM 1733593 ER PT J AU SIDRANSKY, E TSUJI, S STUBBLEFIELD, BK CURRIE, J FITZGIBBON, EJ GINNS, EI AF SIDRANSKY, E TSUJI, S STUBBLEFIELD, BK CURRIE, J FITZGIBBON, EJ GINNS, EI TI GAUCHER PATIENTS WITH OCULOMOTOR ABNORMALITIES DO NOT HAVE A UNIQUE GENOTYPE SO CLINICAL GENETICS LA English DT Article DE GLUCOCEREBROSIDASE; MUTATIONS; PHENOTYPE; NEUROOPHTHALMOLOGICAL; SACCADES ID ACID BETA-GLUCOSIDASE; HUMAN GLUCOCEREBROSIDASE; DISEASE; GENE; MUTATIONS; AMPLIFICATION; PHENOTYPES; SEQUENCE; SIBLINGS; ALLELES AB Sixteen non-Ashkenazic American children with Gaucher disease who demonstrate slowing of the horizontal saccades are described. Attempts to correlate this specific clinical phenotype with a unique genotype were unsuccessful. Focusing on the three most common mutations, at least five different genotypes were present in these patients. Children with this isolated oculomotor abnormality generally had a diffusely slowed background on EEG, but an otherwise normal neurologic examination, and exhibited earlier and more severe systemic manifestations and mortality. This study emphasizes the need for careful sequential neuro-ophthalmologic examinations in Gaucher patients and the need for caution in attempting to make clinical predictions regarding the course of Gaucher disease on the basis of current DNA mutational analysis. C1 MENTAL HLTH RES INST VICTORIA,PARKVILLE,VIC,AUSTRALIA. NEI,SENSORY MOTOR RES LAB,BETHESDA,MD 20892. RP SIDRANSKY, E (reprint author), NIMH,IRP,CLIN NEUROSCI BRANCH,MOLEC NEUROGENET SECT,BLDG 10,ROOM 3D16,BETHESDA,MD 20892, USA. NR 28 TC 18 Z9 18 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD JAN PY 1992 VL 41 IS 1 BP 1 EP 5 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA HF236 UT WOS:A1992HF23600001 PM 1633639 ER PT J AU FRANK, MM BASTA, M FRIES, LF AF FRANK, MM BASTA, M FRIES, LF TI THE EFFECTS OF INTRAVENOUS IMMUNE GLOBULIN ON COMPLEMENT-DEPENDENT IMMUNE DAMAGE OF CELLS AND TISSUES SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article; Proceedings Paper CT SYMP ON FUTURE DIRECTIONS OF CYTOKINE AND IMMUNOGLOBULIN THERAPY CY JAN 11-12, 1991 CL TUCSON, AZ SP MILES, PHARM DIV, CUTTER BIOL ID IMMUNOGLOBULIN C1 NIAID,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD 21205. RP FRANK, MM (reprint author), DUKE UNIV,MED CTR,DEPT PEDIAT,DURHAM,NC 27710, USA. NR 6 TC 73 Z9 73 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD JAN PY 1992 VL 62 IS 1 BP S82 EP S86 DI 10.1016/0090-1229(92)90045-P PN 2 PG 5 WC Immunology; Pathology SC Immunology; Pathology GA GZ022 UT WOS:A1992GZ02200012 PM 1728991 ER PT J AU KENNEY, RT KWONCHUNG, KJ WAYTES, AT MELNICK, DA PASS, HI MERINO, MJ GALLIN, JI AF KENNEY, RT KWONCHUNG, KJ WAYTES, AT MELNICK, DA PASS, HI MERINO, MJ GALLIN, JI TI SUCCESSFUL TREATMENT OF SYSTEMIC EXOPHIALA-DERMATITIDIS INFECTION IN A PATIENT WITH CHRONIC GRANULOMATOUS-DISEASE SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID WANGIELLA-DERMATITIDIS; PHAEOHYPHOMYCOSIS; THERAPY; CLONING; OXIDASE; GENE AB Exophiala dermatitidis, one of the saprophytic dematiaceous fungi, is a rare cause of human infection that, when invasive, is nearly always fatal. Besides the more common subcutaneous infection usually caused by traumatic inoculation, infection can also spread hematogenously, in which case the organism has a distinct neurotropism. A patient with autosomal recessive chronic granulomatous disease of childhood who was found to have a progressive pulmonary and central nervous system infection with E. dermatitidis responded to an aggressive, multifaceted therapeutic approach. Scanning electron microscopy of the cultured conidiogenous cells confirmed that the manner of conidiogenesis is typical of the genus Exophiala. We report the first successful treatment of an infection involving the lungs and central nervous system by a combination of surgical resection of the pulmonary source and medical therapy with amphotericin B, flucytosine or ketoconazole, and transfused white cells, followed by a prolonged course of fluconazole. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. RP KENNEY, RT (reprint author), NIAID,HOST DEF & CLIN INVEST LABS,BLDG 10,ROOM 11N110,BETHESDA,MD 20892, USA. NR 33 TC 54 Z9 54 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN PY 1992 VL 14 IS 1 BP 235 EP 242 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA HD517 UT WOS:A1992HD51700039 PM 1571438 ER PT J AU KUSEK, JW HIRSCHMAN, GH AGODOA, L STRIKER, GE AF KUSEK, JW HIRSCHMAN, GH AGODOA, L STRIKER, GE TI NEPHROLOGY CLINICAL-TRIALS SUPPORTED BY THE KIDNEY PROGRAMS OF THE NATIONAL INSTITUTES OF HEALTH SO CLINICAL NEPHROLOGY LA English DT Article ID RENAL-DISEASE C1 NIDDKD,DIV KIDNEY UROL & HEMATOL DIS,BETHESDA,MD. NR 13 TC 0 Z9 0 U1 0 U2 0 PU DUSTRI-VERLAG DR KARL FEISTLE PI MUNCHEN-DEISENHOFEN PA BAHNHOFSTRABE 9 POSTFACH 49, W-8024 MUNCHEN-DEISENHOFEN, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PY 1992 VL 38 SU 1 BP S61 EP S63 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA KR807 UT WOS:A1992KR80700010 PM 1295710 ER PT J AU HOBBS, S NEUMANN, RD MERINO, MJ GUNZENHAUSER, J CARRASQUILLO, JA AF HOBBS, S NEUMANN, RD MERINO, MJ GUNZENHAUSER, J CARRASQUILLO, JA TI LOCALIZATION OF TC-99M MDP IN CYSTOSARCOMA-PHYLLODES SO CLINICAL NUCLEAR MEDICINE LA English DT Note ID CARCINOMA; BREAST C1 NCI,CTR CLIN,DEPT NUCL MED,9000 ROCKVILLE PIKE,BLDG 10,ROOM 1C-401,BETHESDA,MD 20982. NCI,PATHOL LAB,BETHESDA,MD 20982. HARVARD UNIV,SCH MED,BOSTON,MA 02115. ALBANY MED COLL,SCH MED,ALBANY,NY 12208. RI Carrasquillo, Jorge/E-7120-2010 NR 7 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-9762 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD JAN PY 1992 VL 17 IS 1 BP 58 EP 60 DI 10.1097/00003072-199201000-00019 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA HA595 UT WOS:A1992HA59500019 PM 1312001 ER PT J AU CALIS, KA KOHLER, DR CORSO, DM AF CALIS, KA KOHLER, DR CORSO, DM TI TRANSDERMALLY ADMINISTERED FENTANYL FOR PAIN MANAGEMENT SO CLINICAL PHARMACY LA English DT Article DE ANALGESICS AND ANTIPYRETICS; BLOOD LEVELS; DOSAGE FORMS; DRUG ADMINISTRATION ROUTES; FENTANYL; PATCHES TRANSDERMAL; PHARMACOKINETICS; TOPICAL PREPARATIONS; TOXICITY AB The physicochemical properties, pharmacology, pharmacokinetics, serum concentrations and clinical effects, adverse effects and contraindications, and dosage of transdermally administered fentanyl are described, and clinical studies evaluating the use of a transdermal fentanyl system in the treatment of postoperative pain and chronic cancer-associated pain are reviewed. After application of a transdermal system, fentanyl is absorbed into the skin beneath the patch, where a depot forms in the upper skin layers. Plasma fentanyl concentrations are barely detectable for about two hours after patch placement. Eight to 12 hours after patch placement, concentrations approximate those achieved with equivalent i.v. doses of fentanyl. Some studies comparing transdermally administered fentanyl with placebo in postoperative patients showed that the patients who received fentanyl required fewer supplementary analgesics and reported less pain than the patients who received placebo. However, the overall efficacy and safety of the transdermal fentanyl system for the treatment of postoperative pain have not been adequately evaluated. Studies of cancer patients showed that transdermally administered fentanyl appears to be effective in the management of chronic, cancer-related pain. Dermatological reactions to the fentanyl patch are generally transient and mild. Other adverse effects are those that are commonly associated with narcotic analgesics. The 25-mu-g/hr patch should be used for initial treatment in patients not previously treated with narcotics. The dosage may be gradually increased until effective analgesia is obtained. Although experience with the product is limited, transdermally administered fentanyl appears to be effective for the long-term management of cancer-related pain. RP CALIS, KA (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DRUG INFORMAT SERV,BLDG 10,ROOM 1N-257,BETHESDA,MD 20892, USA. NR 0 TC 62 Z9 62 U1 1 U2 6 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 0278-2677 J9 CLIN PHARMACY PD JAN PY 1992 VL 11 IS 1 BP 22 EP 36 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GW251 UT WOS:A1992GW25100007 PM 1730176 ER PT B AU KUHAR, MJ AF KUHAR, MJ BE BOCK, GR WHELAN, J TI MOLECULAR PHARMACOLOGY OF COCAINE - A DOPAMINE HYPOTHESIS AND ITS IMPLICATIONS SO COCAINE : SCIENTIFIC AND SOCIAL DIMENSIONS SE CIBA FOUNDATION SYMPOSIA LA English DT Proceedings Paper CT SYMP ON COCAINE : SCIENTIFIC AND SOCIAL DIMENSIONS CY JUL 20-22, 1991 CL CIBA FDN, LONDON, ENGLAND SP CIBA FDN HO CIBA FDN ID RAT STRIATUM; UPTAKE SITES; INTRAVENOUS COCAINE; NONHUMAN-PRIMATES; LIGAND-BINDING; RECEPTORS; SEROTONIN; DRUGS; TRANSPORTERS; INHIBITION RP KUHAR, MJ (reprint author), NIDA,ADDICT RES CTR,NEUROSCI BRANCH,POB 5180,BALTIMORE,MD 21224, USA. NR 0 TC 45 Z9 45 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA CHICHESTER BN 0-471-93179-9 J9 CIBA F SYMP PY 1992 VL 166 BP 81 EP 95 PG 15 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry; Psychology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology GA BV65D UT WOS:A1992BV65D00006 PM 1638923 ER PT J AU PARADA, LF TSOULFAS, P TESSAROLLO, L BLAIR, J REID, SW SOPPET, D AF PARADA, LF TSOULFAS, P TESSAROLLO, L BLAIR, J REID, SW SOPPET, D TI THE TRK FAMILY OF TYROSINE KINASES - RECEPTORS FOR NGF-RELATED NEUROTROPHINS SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article ID NERVE GROWTH-FACTOR; PROTOONCOGENE PRODUCT; MOLECULAR-CLONING; NEURAL CREST; SPINAL GANGLIA; EXPRESSION; PROTEIN; MEMBER; BRAIN; GENE RP PARADA, LF (reprint author), NCI,FREDERICK CANC RES & DEV CTR,MOLEC EMBRYOL SECT,ABL BASIC RES PROGRAM,FREDERICK,MD 21702, USA. RI Parada, luis/B-9400-2014; OI Tsoulfas, Pantelis/0000-0003-1974-6366 FU NCI NIH HHS [N01-CO-74101] NR 45 TC 49 Z9 49 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 1992 VL 57 BP 43 EP 51 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA LV416 UT WOS:A1992LV41600004 PM 1339678 ER PT J AU JOHNSON, RL GUNDERSEN, R HERELD, D PITT, GS TUGENDREICH, S SAXE, CL KIMMEL, AR DEVREOTES, PN AF JOHNSON, RL GUNDERSEN, R HERELD, D PITT, GS TUGENDREICH, S SAXE, CL KIMMEL, AR DEVREOTES, PN TI G-PROTEIN-LINKED SIGNALING PATHWAYS MEDIATE DEVELOPMENT IN DICTYOSTELIUM SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article ID SURFACE CAMP RECEPTORS; BETA-ADRENERGIC-RECEPTOR; CYCLIC-AMP RECEPTOR; CELL-SURFACE; ADENYLATE-CYCLASE; MULTICELLULAR DEVELOPMENT; GENE-EXPRESSION; ALPHA-SUBUNITS; DISCOIDEUM; BINDING C1 NIDDKD 6B112,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892. RP JOHNSON, RL (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT BIOL CHEM,BALTIMORE,MD 21205, USA. FU NCRR NIH HHS [SO-7 RR-05364]; NIGMS NIH HHS [GM-28007, GM-34933] NR 53 TC 15 Z9 15 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 1992 VL 57 BP 169 EP 176 PG 8 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA LV416 UT WOS:A1992LV41600020 PM 1339656 ER PT J AU YAMADA, KM AOTA, S AKIYAMA, SK LAFLAMME, SE AF YAMADA, KM AOTA, S AKIYAMA, SK LAFLAMME, SE TI MECHANISMS OF FIBRONECTIN AND INTEGRIN FUNCTION DURING CELL-ADHESION AND MIGRATION SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; HUMAN-PLASMA FIBRONECTIN; III CONNECTING SEGMENT; NEURAL CREST CELLS; BINDING DOMAIN; EXTRACELLULAR-MATRIX; SYNTHETIC PEPTIDES; MONOCLONAL-ANTIBODY; FIBROBLASTIC CELLS; AMPHIBIAN EMBRYOS RP YAMADA, KM (reprint author), NIDR,DEV BIOL LAB,BETHESDA,MD 20892, USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 70 TC 38 Z9 38 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 1992 VL 57 BP 203 EP 212 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA LV416 UT WOS:A1992LV41600023 PM 1339659 ER PT J AU HEDRICK, L CHO, KR BOYD, J RISINGER, J VOGELSTEIN, B AF HEDRICK, L CHO, KR BOYD, J RISINGER, J VOGELSTEIN, B TI DCC - A TUMOR-SUPPRESSOR GENE EXPRESSED ON THE CELL-SURFACE SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article ID COLORECTAL CANCERS; DIFFERENTIATION; IDENTIFICATION; DELETIONS; MUTATIONS; ONCOGENES C1 JOHNS HOPKINS UNIV,SCH MED,CTR ONCOL,BALTIMORE,MD 21205. NIEHS,MOLEC CARCINOGENESIS LAB,GENE EXPRESS SECT,RES TRIANGLE PK,NC 27709. RP HEDRICK, L (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205, USA. FU NCI NIH HHS [CA-43460] NR 22 TC 28 Z9 29 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 1992 VL 57 BP 345 EP 351 PG 7 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA LV416 UT WOS:A1992LV41600037 PM 1339669 ER PT B AU WEINSTEIN, JN BUNOW, B AF WEINSTEIN, JN BUNOW, B BE GOLDSTEIN, AL GARACI, E TI COMBO - NEW CONCEPTS AND METHODS FOR DESIGNING AND ANALYZING EXPERIMENTS ON COMBINATION THERAPY SO COMBINATION THERAPIES: BIOLOGICAL RESPONSE MODIFIERS IN THE TREATMENT OF CANCER AND INFECTIOUS DISEASES LA English DT Proceedings Paper CT 1ST INTERNATIONAL SYMP ON COMBINATION THERAPIES : NEW AND EMERGING USES FOR BIOLOGICAL RESPONSE MODIFIERS IN THE TREATMENT OF CANCER AND INFECTIOUS DISEASES CY MAR 14-15, 1991 CL GEORGE WASHINGTON UNIV, WASHINGTON, DC SP GEORGE WASHINGTON UNIV, SCH MED, INST ADV STUDIES IMMUNOL & AGING, UNIV ROME TOR VERGATA HO GEORGE WASHINGTON UNIV RP WEINSTEIN, JN (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA NEW YORK BN 0-306-44115-2 PY 1992 BP 29 EP 38 PG 10 WC Biochemistry & Molecular Biology; Oncology; Immunology; Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Oncology; Immunology; Microbiology; Pharmacology & Pharmacy GA BV54N UT WOS:A1992BV54N00004 ER PT B AU EVANS, CH FURBERTHARRIS, PM FLUGELMAN, AA WOODWORTH, CD DIPAOLO, JA AF EVANS, CH FURBERTHARRIS, PM FLUGELMAN, AA WOODWORTH, CD DIPAOLO, JA BE GOLDSTEIN, AL GARACI, E TI SYNERGISTIC REGULATION OF LAK LYMPHOCYTE CYTOTOXICITY BY COMBINATION CYTOKINE AND CISPLATIN TREATMENT SO COMBINATION THERAPIES: BIOLOGICAL RESPONSE MODIFIERS IN THE TREATMENT OF CANCER AND INFECTIOUS DISEASES LA English DT Proceedings Paper CT 1ST INTERNATIONAL SYMP ON COMBINATION THERAPIES : NEW AND EMERGING USES FOR BIOLOGICAL RESPONSE MODIFIERS IN THE TREATMENT OF CANCER AND INFECTIOUS DISEASES CY MAR 14-15, 1991 CL GEORGE WASHINGTON UNIV, WASHINGTON, DC SP GEORGE WASHINGTON UNIV, SCH MED, INST ADV STUDIES IMMUNOL & AGING, UNIV ROME TOR VERGATA HO GEORGE WASHINGTON UNIV RP EVANS, CH (reprint author), NCI,BIOL LAB,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA NEW YORK BN 0-306-44115-2 PY 1992 BP 237 EP 244 PG 8 WC Biochemistry & Molecular Biology; Oncology; Immunology; Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Oncology; Immunology; Microbiology; Pharmacology & Pharmacy GA BV54N UT WOS:A1992BV54N00029 ER PT B AU WILTROUT, RH DAMIA, G MACPHEE, M FUTAMI, H FALTYNEK, CR LONGO, DL RUSCETTI, FW KOMSCHLIES, KL AF WILTROUT, RH DAMIA, G MACPHEE, M FUTAMI, H FALTYNEK, CR LONGO, DL RUSCETTI, FW KOMSCHLIES, KL BE GOLDSTEIN, AL GARACI, E TI CYTOKINE-BASED COMBINED MODALITY APPROACHES TO THE TREATMENT OF MURINE RENAL-CANCER SO COMBINATION THERAPIES: BIOLOGICAL RESPONSE MODIFIERS IN THE TREATMENT OF CANCER AND INFECTIOUS DISEASES LA English DT Proceedings Paper CT 1ST INTERNATIONAL SYMP ON COMBINATION THERAPIES : NEW AND EMERGING USES FOR BIOLOGICAL RESPONSE MODIFIERS IN THE TREATMENT OF CANCER AND INFECTIOUS DISEASES CY MAR 14-15, 1991 CL GEORGE WASHINGTON UNIV, WASHINGTON, DC SP GEORGE WASHINGTON UNIV, SCH MED, INST ADV STUDIES IMMUNOL & AGING, UNIV ROME TOR VERGATA HO GEORGE WASHINGTON UNIV RP WILTROUT, RH (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PRESS DIV PLENUM PUBLISHING CORP PI NEW YORK PA NEW YORK BN 0-306-44115-2 PY 1992 BP 269 EP 274 PG 6 WC Biochemistry & Molecular Biology; Oncology; Immunology; Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Oncology; Immunology; Microbiology; Pharmacology & Pharmacy GA BV54N UT WOS:A1992BV54N00032 ER PT J AU PARK, T WOOLSON, RF AF PARK, T WOOLSON, RF TI GENERALIZED MULTIVARIATE MODELS FOR LONGITUDINAL DATA SO COMMUNICATIONS IN STATISTICS-SIMULATION AND COMPUTATION LA English DT Article DE LONGITUDINAL DATA; MISSING DATA; REPEATED MEASURES ANALYSIS; SEEMINGLY UNRELATED REGRESSIONS ID SEEMINGLY UNRELATED REGRESSION; REPEATED MEASURES DESIGNS; GROWTH CURVE MODELS; MAXIMUM-LIKELIHOOD; EM-ALGORITHM; INFERENCE AB A general class of multivariate models is proposed for unbalanced and incomplete longitudinal data. The proposed model is an extension of the seemingly unrelated regression model (Zellner, 1962). The advantage of this model is discussed regarding its applicability to a larger class of problems and the ease of estimation. The application of the model includes the model for the time varying covariates proposed by Patel (1988) and growth curve models. Two estimation methods are considered; one method is the generalized least squares method based on Zellner's noniterative two-stage estimation and the other is the iterative maximum likelihood estimation method using the EM algorithm (Dempster, Laird, and Rubin, 1977). Simulation studies are conducted to compare the small sample properties of the two estimators. C1 NICHHD,EPN,BETHESDA,MD 20892. UNIV IOWA,DEPT PREVENT MED & ENVIRONM HLTH,IOWA CITY,IA 52242. NR 18 TC 3 Z9 3 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0361-0918 J9 COMMUN STAT SIMULAT JI Commun. Stat.-Simul. Comput. PY 1992 VL 21 IS 4 BP 925 EP 946 DI 10.1080/03610919208813059 PG 22 WC Statistics & Probability SC Mathematics GA JU837 UT WOS:A1992JU83700001 ER PT J AU WILLIAMS, PL PORTIER, CJ AF WILLIAMS, PL PORTIER, CJ TI ANALYTIC EXPRESSIONS FOR MAXIMUM-LIKELIHOOD ESTIMATORS IN A NONPARAMETRIC MODEL OF TUMOR-INCIDENCE AND DEATH SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE ANIMAL CARCINOGENICITY EXPERIMENTS; MAXIMUM LIKELIHOOD METHODS; NONPARAMETRIC ESTIMATION; SIMULATION STUDY; SURVIVAL SACRIFICE DATA; TUMOR INCIDENCE RATE ID ANIMAL CARCINOGENESIS EXPERIMENTS; SURVIVAL SACRIFICE EXPERIMENTS; PREVALENCE; TESTS; MORTALITY AB This research focuses on the estimation of tumor incidence rates from long-term animal studies which incorporate interim sacrifices. A nonparametric stochastic model is described with transition rates between states corresponding to the tumor incidence rate, the overall death rate, and the death rate for tumor-free animals. Exact analytic solutions for the maximum likelihood estimators of the hazard rates are presented, and their application to data from a long-term animal study is illustrated by an example. Unlike many common methods for estimation and comparison of tumor incidence rates among treatment groups, the estimators derived in this paper require no assumptions regarding tumor lethality or treatment lethality. The small sample operating characteristics of these estimators are evaluated using Monte Carlo simulation studies. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. NIEHS,DIV BIOMETRY & RISK ASSESSMENT,RES TRIANGLE PK,NC 27709. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 28 TC 9 Z9 9 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0361-0926 J9 COMMUN STAT THEORY JI Commun. Stat.-Theory Methods PY 1992 VL 21 IS 3 BP 711 EP 732 DI 10.1080/03610929208830810 PG 22 WC Statistics & Probability SC Mathematics GA HK202 UT WOS:A1992HK20200013 ER PT J AU FREY, CM MULLER, KE AF FREY, CM MULLER, KE TI ANALYSIS-METHODS FOR NONLINEAR MODELS WITH COMPOUND-SYMMETRICAL COVARIANCE SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE INCOMPLETE DATA; REPEATED MEASUREMENTS; WEIGHTED LEAST SQUARES; MAXIMUM LIKELIHOOD; TYPE-I ERROR ID REGRESSION AB Existing general methods for fitting nonlinear multivariate regression functions produce standard errors for parameter estimates which can be extremely optimistic when small samples are used. By incorporating the compound-symmetric covariance structure into the model where appropriate, substantial improvements in the estimation of the covariance matrix for the parameter estimates may be expected. An approximate weighted least squares method is described for fitting a nonlinear response function to repeated measures data with compound-symmetric covariance for each independent sampling unit. The method is applicable to incomplete data. Under regularity conditions, the estimation procedure yields asymptotically normal, unbiased and consistent estimators. With complete Gaussian data, the procedure may be iterated to produce maximum likelihood estimates of response function parameters and variance components. Hypothesis testing following estimation procedures which either ignore or address the compound symmetry in simulated data are compared. Substantially smaller sample sizes are shown to yield the correct Type I error in the latter case. C1 NCI,BETHESDA,MD 20892. UNIV NORTH CAROLINA,DEPT BIOSTAT,CHAPEL HILL,NC 27599. NR 27 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0361-0926 J9 COMMUN STAT THEORY JI Commun. Stat.-Theory Methods PY 1992 VL 21 IS 5 BP 1163 EP 1182 DI 10.1080/03610929208830839 PG 20 WC Statistics & Probability SC Mathematics GA HR068 UT WOS:A1992HR06800001 ER PT J AU FOLLMANN, DA AF FOLLMANN, DA TI GROWTH CURVE MODELS WITH RESTRICTIONS ON RANDOM PARAMETERS SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE EMPIRICAL BAYES; EM ALGORITHM; RANDOM EFFECTS; REPEATED MEASURES ID EM-ALGORITHM; MAXIMUM-LIKELIHOOD; LINEAR-MODEL; INFERENCE AB In the classical growth curve setting, individuals are repeatedly measured over time on an outcome of interest. The objective of statistical modeling is to fit some function of time, generally a polynomial, that describes the outcome's behavior. The polynomial coefficients are assumed drawn from a multivariate normal mixing distribution. At times, it may be known that each individual's polynomial must follow a restricted form. When the polynomial coefficients lie close to the restriction boundary, or the outcome is subject to substantial measurement error, or relatively few observations per individual are recorded, it can be advantageous to incorporate known restrictions. This paper introduces a class of models where the polynomial coefficients are assumed drawn from a restricted multivariate normal whose support is confined to a theoretically permissible region. The model can handle a variety of restrictions on the space of random parameters. The restricted support ensures that each individual's random polynomial is theoretically plausible. Estimation, posterior calculations, and comparisons with the unrestricted approach are provided. C1 NATL HEART LUNG & BLOOD INST,BIOSTAT RES BRANCH,BETHESDA,MD 20892. NR 32 TC 0 Z9 0 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0361-0926 J9 COMMUN STAT THEORY JI Commun. Stat.-Theory Methods PY 1992 VL 21 IS 10 BP 2775 EP 2795 DI 10.1080/03610929208830943 PG 21 WC Statistics & Probability SC Mathematics GA JR200 UT WOS:A1992JR20000003 ER PT J AU NUSSINOV, R AF NUSSINOV, R TI DNA SPATIAL CONSIDERATIONS IN THE ARRANGEMENT OF G/C AND A/T BLOCKS SO COMPUTERS IN BIOLOGY AND MEDICINE LA English DT Article DE DNA SEQUENCE PATTERNS; COMPUTER ANALYSIS OF DNA SEQUENCES; DNA STRUCTURE PARAMETERS; SEQUENCE STRUCTURE RELATIONSHIP; SPATIAL POSITIONING OF DNA SEQUENCE ELEMENTS; ROLE OF DNA FLEXIBILITY ID SEQUENCE DEPENDENCE; CONFORMATION; DODECAMER; ORIGIN AB Intensive computations have been carried out on eukaryotic and prokaryotic DNA sequences present in the GenBank database. These calculations were aimed at studying particular sequence patterns. Previously we have observed a trend in the relative positioning of DNA oligomers with respect to each other. Specifically, we have shown that there is a preference for A/T stretches to be inserted inside G/C blocks, partitioning the latter. This arrangement is preferred over having a longer G/C block with an A/T stretch next to it. That is (G/C)n(A/T)m(G/C)2 > (G/C)n+2(A/T)m. Previously we have attributed this preferred pattern to nucleosome packaging of the DNA. Since the average length of the DNA involved in a single nucleosome formation is 200 bp, oligomers were scored in the analysis only if two identical ones occurred within that distance. Since, in addition, the total length of the oligomers studied is n + m + 2 less-than-or-equal-to 7, the counts of the longer oligomers were quite low. Here we have repeated the analysis on the newer, larger database, with that restriction removed. Our new analysis confirms and strengthens the older findings. Moreover, we have carried out DNA structural analysis of these trends, focusing on the twist and roll angular parameters. We have obtained these values from detailed structural computations on the Cray super computer. Some correlations between these values, DNA flexibility and the sequence trends are observed. We suggest that the positioning of the (A/T)m sequence stretch between the two (G/C) blocks affords greater flexibility in the spatial positioning of the G/C sequence elements. C1 TEL AVIV UNIV,SACKLER FAC MED,INST MOLEC MED,IL-69978 TEL AVIV,ISRAEL. RP NUSSINOV, R (reprint author), NCI,FREDERICK CANC RES FACIL,PRI DYNACORP,MATH BIOL LAB,BLDG 469,ROOM 151,FREDERICK,MD 21702, USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0010-4825 J9 COMPUT BIOL MED JI Comput. Biol. Med. PD JAN-MAR PY 1992 VL 22 IS 1-2 BP 97 EP 112 DI 10.1016/0010-4825(92)90055-R PG 16 WC Biology; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Computer Science; Engineering; Mathematical & Computational Biology GA HN345 UT WOS:A1992HN34500009 PM 1572167 ER PT J AU SNEIDERMAN, CA BICKNELL, EJ AF SNEIDERMAN, CA BICKNELL, EJ TI COMPUTER-ASSISTED DYNAMIC INTEGRATION OF MULTIPLE MEDICAL THESAURUSES SO COMPUTERS IN BIOLOGY AND MEDICINE LA English DT Article DE NATURAL LANGUAGE PROCESSING; THESAURUS; ARTIFICIAL INTELLIGENCE; EXPERT SYSTEMS AB We have previously described a user-interactive rule-based computer program (Dyna-SaurI) designed for dynamic thesaurus integration, and demonstrated its efficacy on integrating dermatological subsets of the MeSH and SNOMED thesauruses. In the present study, we have refined our rules for merging and mapping multiple thesauruses and tested these rules. We then applied them with a set of optimized parameters to the integration of a third thesaurus, a subset of the International Coding Index for Dermatology, with the Integrated MeSH-SNOMED thesaurus. The parameter changes resulted in improved ranking of more specific and conceptually closer terms. C1 NIMH,MOLEC BIOL LAB,BETHESDA,MD 20892. RP SNEIDERMAN, CA (reprint author), NATL LIB MED,BETHESDA,MD 20894, USA. NR 13 TC 1 Z9 1 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0010-4825 J9 COMPUT BIOL MED JI Comput. Biol. Med. PD JAN-MAR PY 1992 VL 22 IS 1-2 BP 135 EP 145 DI 10.1016/0010-4825(92)90058-U PG 11 WC Biology; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Computer Science; Engineering; Mathematical & Computational Biology GA HN345 UT WOS:A1992HN34500012 PM 1572160 ER PT J AU MOUTSIAKIS, D MANCUSO, P KRUTZSCH, H STETLERSTEVENSON, W ZUCKER, S AF MOUTSIAKIS, D MANCUSO, P KRUTZSCH, H STETLERSTEVENSON, W ZUCKER, S TI CHARACTERIZATION OF METALLOPROTEINASES AND TISSUE INHIBITORS OF METALLOPROTEINASES IN HUMAN PLASMA SO CONNECTIVE TISSUE RESEARCH LA English DT Article DE TYPE-IV COLLAGENASE; GELATINASE; STROMELYSIN; TIMP; ALPHA-2-MACROGLOBULIN ID BASEMENT-MEMBRANE COLLAGEN; IV COLLAGENASE; MONOCLONAL-ANTIBODIES; MELANOMA-CELLS; TUMOR-CELLS; GELATINASE; STROMELYSIN; ENZYME; EXPRESSION; IDENTIFICATION AB In this study, we have identified and characterized metalloproteinases and tissue inhibitors of metalloproteinases (TIMPs) in human plasma. Treatment of plasma with trypsin or aminophenylmercuric acetate resulted in activation of latent gelatinolytic activity. Fractionation of plasma by gelatin Sepharose chromatography resulted in the isolation of 72 kDa and 92 kDa gelatinases/type IV collagenases. The 72 kDa gelatinase was purified by gel filtration chromatography Stromelysin-1 was isolated from plasma by Matrex green A affinity chromatography. Immunoblotting of plasma fractions with antibodies to unique peptide regions of human gelatinases differentiated the 72 kDa gelatinase from the 92 kDa gelatinase. Antibodies to die amino terminal peptides of each enzyme were used to determine that plasma gelatinases circulate as latent proenzymes, Immunoblotting with antibodies directed against human stromelysin identified a 57 kDa stromelysin. TIMP-1 (28 kDa) and TIMP-2 (21 kDa) were also identified by immunoblotting of gelatin Sepharose bound plasma proteins using non-crossreacting antibodies to each protein. C1 DEPT VET AFFAIRS MED CTR,DEPT RES,151,NORTHPORT,NY 11768. DEPT VET AFFAIRS MED CTR,DEPT MED,NORTHPORT,NY 11768. SUNY STONY BROOK,SCH MED,DEPT MED,STONY BROOK,NY 11794. NCI,DEPT PATHOL,BETHESDA,MD 20892. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 35 TC 58 Z9 58 U1 0 U2 0 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 0300-8207 J9 CONNECT TISSUE RES JI Connect. Tissue Res. PY 1992 VL 28 IS 3 BP 213 EP 230 DI 10.3109/03008209209015038 PG 18 WC Cell Biology; Orthopedics SC Cell Biology; Orthopedics GA JT720 UT WOS:A1992JT72000006 PM 1468208 ER PT B AU MECKLENBURG, RE AF MECKLENBURG, RE BE Gupta, PC Hamner, JE Murti, PR TI ROLE OF DENTAL PROFESSIONALS IN REDUCING TOBACCO USE SO CONTROL OF TOBACCO-RELATED CANCERS AND OTHER DISEASES LA English DT Proceedings Paper CT International Symposium on the Control of Tobacco-related Cancers and Other Diseases CY JAN 15-19, 1990 CL TATA INST FUNDAMENTAL RES, BOMBAY, INDIA SP TATA INST FUNDAMENTAL RES HO TATA INST FUNDAMENTAL RES C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI NEW YORK PA 198 MADISON AVENUE, NEW YORK, NY 10016 BN 0-19-562961-2 PY 1992 BP 271 EP 275 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA BA88C UT WOS:A1992BA88C00029 ER PT B AU GLYNN, TJ SHOPLAND, DR PECHACEK, TF BOYD, GM AF GLYNN, TJ SHOPLAND, DR PECHACEK, TF BOYD, GM BE Gupta, PC Hamner, JE Murti, PR TI CANCER PREVENTION THROUGH A NATIONAL PROGRAM OF RESEARCH INTO A CONTROL OF TOBACCO USE - THE EXPERIENCE OF THE US-NATIONAL-CANCER-INSTITUTE SO CONTROL OF TOBACCO-RELATED CANCERS AND OTHER DISEASES LA English DT Proceedings Paper CT International Symposium on the Control of Tobacco-related Cancers and Other Diseases CY JAN 15-19, 1990 CL TATA INST FUNDAMENTAL RES, BOMBAY, INDIA SP TATA INST FUNDAMENTAL RES HO TATA INST FUNDAMENTAL RES C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI NEW YORK PA 198 MADISON AVENUE, NEW YORK, NY 10016 BN 0-19-562961-2 PY 1992 BP 287 EP 300 PG 14 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA BA88C UT WOS:A1992BA88C00031 ER PT J AU BAUM, BJ SHIP, JA WU, AJ AF BAUM, BJ SHIP, JA WU, AJ TI SALIVARY-GLAND FUNCTION AND AGING - A MODEL FOR STUDYING THE INTERACTION OF AGING AND SYSTEMIC-DISEASE SO CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE LA English DT Article DE GERIATRICS; SALIVATION; ORAL HEALTH; SJOGRENS SYNDROME AB This review describes an approach to examining the interaction of aging and systemic disease on a key aspect of oral physiology, salivation. The approach requires several steps: defining general health, and a specific physiological function, at different ages; defining a disease of interest and the influence of the disease on the specific physiological function; and determining if the disease can affect performance of the physiological function with increased age. RP BAUM, BJ (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 28 Z9 30 U1 0 U2 1 PU INT AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 SN 1045-4411 J9 CRIT REV ORAL BIOL M JI Crit. Rev. Oral Biol. Med. PY 1992 VL 4 IS 1 BP 53 EP 64 PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA KA124 UT WOS:A1992KA12400002 PM 1457685 ER PT J AU RIPAMONTI, U REDDI, AH AF RIPAMONTI, U REDDI, AH TI GROWTH AND MORPHOGENETIC FACTORS IN BONE INDUCTION - ROLE OF OSTEOGENIN AND RELATED BONE MORPHOGENETIC PROTEINS IN CRANIOFACIAL AND PERIODONTAL BONE REPAIR SO CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE LA English DT Article DE EXTRACELLULAR MATRIX (ECM); GROWTH AND MORPHOGENETIC FACTORS; INDUCTIVE INTERACTIONS; BONE MATRIX; ENDOCHONDRAL BONE AB Bone has considerable potential for repair as illustrated by the phenomenon of fracture healing. Repair and regeneration of bone recapitulate the sequential stages of development. It is well known that demineralized bone matrix has the potential to induce new bone formation locally at a heterotopic site of implantation. The sequential development of bone is reminiscent of endochondral bone differentiation during bone development. The collagenous matrix-induced bone formation is a prototype model for matrix-cell interactions in vivo. The developmental cascade includes migration of progenitor cells by chemotaxis, attachment of cells through fibronectin, proliferation of mesenchymal cells, and differentiation of bone. The bone inductive protein, osteogenin, was isolated by heparin affinity chromatography. Osteogenin initiates new bone formation and is promoted by other growth factors. Recently, the genes for osteogenin and related bone morphogenetic proteins were cloned and expressed. Recombinant osteogenin is osteogenic in vivo. The future prospects for bone induction are bright, and this is an exciting frontier with applications in oral and orthopaedic surgery. RP RIPAMONTI, U (reprint author), NIDR,BONE CELL BIOL SECT,BETHESDA,MD 20892, USA. NR 0 TC 38 Z9 41 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 SN 1045-4411 J9 CRIT REV ORAL BIOL M JI Crit. Rev. Oral Biol. Med. PY 1992 VL 3 IS 1-2 BP 1 EP 14 PG 14 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA GU916 UT WOS:A1992GU91600001 PM 1730066 ER PT J AU BEAUCHAMP, RO STCLAIR, MBG FENNELL, TR CLARKE, DO MORGAN, KT KARI, FW AF BEAUCHAMP, RO STCLAIR, MBG FENNELL, TR CLARKE, DO MORGAN, KT KARI, FW TI A CRITICAL-REVIEW OF THE TOXICOLOGY OF GLUTARALDEHYDE SO CRITICAL REVIEWS IN TOXICOLOGY LA English DT Review DE GLUTARALDEHYDE REVIEW; HUMAN TOXICITY; ANIMAL TOXICITY; REPRODUCTIVE TOXICITY; GENOTOXICITY; METABOLISM; TOXICOKINETICS; PROTEIN MACROMOLECULES; ENVIRONMENT; HEALTH EFFECTS; ALDEHYDE COMPOSITION; USES ID ALLERGIC CONTACT-DERMATITIS; A.T BASE-PAIRS; ALDEHYDE DEHYDROGENASE; CELL-PROLIFERATION; AQUEOUS-SOLUTION; LIQUID-CHROMATOGRAPHY; SPONTANEOUS-ABORTIONS; SEGMENTATION MITOSES; VASCULAR PROSTHESES; REGIONAL VARIATIONS AB Glutaraldehyde, a low molecular weight aldehyde, has been investigated for toxicity in humans and animals. Examination of this dialdehyde was indicated from previous studies with other aldehydes in which carcinogenicity of formaldehyde and toxicity of acetaldehyde and malonaldehyde have been disclosed. Information gaps concerning the actions of glutaraldehyde have been identified in this review and recommendations are suggested for additional short- and long-term studies. In particular, information regarding irritation of the respiratory tract, potential neurotoxicity, and developmental effects would assist in a complete hazard evaluation of glutaraldehyde. Further study related to disposition, metabolism, and reactions of glutaraldehyde may elucidate the mechanism of action. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP BEAUCHAMP, RO (reprint author), CHEM IND INST TOXICOL,POB 12137,RES TRIANGLE PK,NC 27709, USA. RI Fennell, Tim/D-9936-2013 NR 242 TC 81 Z9 82 U1 2 U2 16 PU CRC PRESS INC PI BOCA RATON PA 2000 CORPORATE BLVD NW, JOURNALS CUSTOMER SERVICE, BOCA RATON, FL 33431 SN 1040-8444 J9 CRIT REV TOXICOL JI Crit. Rev. Toxicol. PY 1992 VL 22 IS 3-4 BP 143 EP 174 DI 10.3109/10408449209145322 PG 32 WC Toxicology SC Toxicology GA JQ251 UT WOS:A1992JQ25100001 PM 1388704 ER PT J AU WAALKES, MP COOGAN, TP BARTER, RA AF WAALKES, MP COOGAN, TP BARTER, RA TI TOXICOLOGICAL PRINCIPLES OF METAL CARCINOGENESIS WITH SPECIAL EMPHASIS ON CADMIUM SO CRITICAL REVIEWS IN TOXICOLOGY LA English DT Review DE METALS; CADMIUM; CARCINOGENESIS; CANCER; HUMAN; RODENTS; REVIEW ID LOW-MOLECULAR-MASS; DIETARY ZINC-DEFICIENCY; WISTAR CRL-(WI)BR RATS; DOSE-RESPONSE ANALYSIS; CHINESE-HAMSTER CELLS; BINDING-PROTEINS; PRODUCTION WORKERS; CANCER MORTALITY; TUMOR-INDUCTION; PROSTATE-CANCER AB Metals are an important and emerging class of carcinogens. At least three metals, specifically nickel, chromium, and arsenic, are confirmed human carcinogens, and several more are suspected to have carcinogenic potential in man. Considering that the list of known human carcinogens of any type is very small, it becomes clear that metals make up a substantial portion of the list. Furthermore, many metals are very potent carcinogens in laboratory animals. Despite this, relatively little attention has been given to the topic of metal carcinogenesis. The reasons for this relative lack of attention are not clear but perhaps are fostered by a perception that, because metals are the simplest of molecules, their mechanism of action must also be simple. This could not be farther from the truth and, although no clear mechanisms have emerged in the area of metal carcinogenesis, it has become apparent that they are anything but simple. Metal carcinogens possess several unique characteristics including a remarkable target site specificity. Detection of the mechanism, or mechanisms, of metal carcinogenesis has, however, proven elusive, in part because of a wide diversity of metallic carcinogenic agents and the intricate nature of metal interactions in biologic systems. The following review explores this broad topic, with special emphasis on toxicological principles including dose-response relationships and potential mechanisms, using cadmium as an example. RP WAALKES, MP (reprint author), NCJ,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,INORGAN CARCINOGENESIS SECT,FREDERICK,MD 21702, USA. NR 168 TC 214 Z9 224 U1 3 U2 10 PU CRC PRESS INC PI BOCA RATON PA 2000 CORPORATE BLVD NW, JOURNALS CUSTOMER SERVICE, BOCA RATON, FL 33431 SN 1040-8444 J9 CRIT REV TOXICOL JI Crit. Rev. Toxicol. PY 1992 VL 22 IS 3-4 BP 175 EP 201 DI 10.3109/10408449209145323 PG 27 WC Toxicology SC Toxicology GA JQ251 UT WOS:A1992JQ25100002 PM 1388705 ER PT J AU JOHNSON, ES AF JOHNSON, ES TI HUMAN EXPOSURE TO 2,3,7,8-TCDD AND RISK OF CANCER SO CRITICAL REVIEWS IN TOXICOLOGY LA English DT Review DE 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; TCDD; PHENOXYACETIC ACIDS; CHLOROPHENOLS; SOFT-TISSUE SARCOMA; MALIGNANT LYMPHOMA; CANCER ID SOFT-TISSUE SARCOMA; NON-HODGKINS-LYMPHOMA; LICENSED PESTICIDE APPLICATORS; HIGHER CHLORINATED DIOXINS; MALIGNANT-LYMPHOMA; CHEMICAL WORKERS; CASE-REFERENT; NEW-ZEALAND; FOLLOW-UP; MULTIPLE-MYELOMA AB Most of the evidence for the carcinogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in humans has centered around whether it causes malignant lymphomas (ML) and soft-tissue sarcomas (STS). A critical review of the literature indicates that the evidence does not support a causal role for TCDD in the etiology of ML. For STS, the evidence does not specifically incriminate TCDD either, although there is room for doubt. Cancers of other sites, particularly of the respiratory system and thyroid which were found to be statistically significantly in excess in either of the two largest studies of combined cohorts of occupationally exposed workers, were identified as candidate tumors for which a possible etiological role of TCDD might need investigation in future studies. RP JOHNSON, ES (reprint author), NIEHS,DIV BIOMETRY & RISK ASSESSMENT,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709, USA. NR 120 TC 28 Z9 28 U1 2 U2 3 PU CRC PRESS INC PI BOCA RATON PA 2000 CORPORATE BLVD NW, JOURNALS CUSTOMER SERVICE, BOCA RATON, FL 33431 SN 1040-8444 J9 CRIT REV TOXICOL JI Crit. Rev. Toxicol. PY 1992 VL 21 IS 6 BP 451 EP 463 DI 10.3109/10408449209089883 PG 13 WC Toxicology SC Toxicology GA HD206 UT WOS:A1992HD20600003 ER PT J AU MASER, JD DINGES, N AF MASER, JD DINGES, N TI COMORBIDITY - MEANING AND USES IN CROSS-CULTURAL CLINICAL RESEARCH SO CULTURE MEDICINE AND PSYCHIATRY LA English DT Article; Proceedings Paper CT JOINT WORKSHOP OF THE NIMH / INDIAN HEALTH SERVICE - COMORBIDITY AMONG AMERICAN INDIANS AND ALASKA NATIVES : DEPRESSION, ANXIETY, AND SUBSTANCE ABUSE CY APR 08-10, 1991 CL ESTES PK, CO SP NIMH, INDIAN HLTH SERV ID DSM-III-R; DIAGNOSTIC INTERVIEW; DISORDERS; CLASSIFICATION; SCHEDULE; SYMPTOMS; DISEASE AB American Indians and Alaska Natives were the subject of a workshop sponsored by the National Institute of Mental Health and the Indian Health Service. Comorbidity of anxiety, depression, and substance abuse is highly prevalent in these two populations, and this was the focus of the meeting. This paper introduces the topic of psychiatric comorbidity, and considers the topics of culture, psychiatric diagnosis, and assessment. Future research directions and a brief summary of the papers presented at the workshop, which are included in this issue, are provided. C1 UNIV ALASKA,FAIRBANKS,AK 99701. RP MASER, JD (reprint author), NIMH,ROCKVILLE,MD 20857, USA. NR 41 TC 7 Z9 7 U1 2 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0165-005X J9 CULT MED PSYCHIAT JI Cult. Med. Psychiatr. PY 1992 VL 16 IS 4 BP 409 EP 425 PG 17 WC Anthropology; Psychiatry; Social Sciences, Biomedical SC Anthropology; Psychiatry; Biomedical Social Sciences GA LC253 UT WOS:A1992LC25300001 PM 1305523 ER PT J AU BROWN, GL ALBAUGH, BJ ROBIN, RW GOODSON, SG TRUNZO, M WYNNE, DK GOLDMAN, D AF BROWN, GL ALBAUGH, BJ ROBIN, RW GOODSON, SG TRUNZO, M WYNNE, DK GOLDMAN, D TI ALCOHOLISM AND SUBSTANCE-ABUSE AMONG SELECTED SOUTHERN CHEYENNE INDIANS SO CULTURE MEDICINE AND PSYCHIATRY LA English DT Article; Proceedings Paper CT JOINT WORKSHOP OF THE NIMH / INDIAN HEALTH SERVICE - COMORBIDITY AMONG AMERICAN INDIANS AND ALASKA NATIVES : DEPRESSION, ANXIETY, AND SUBSTANCE ABUSE CY APR 08-10, 1991 CL ESTES PK, CO SP NIMH, INDIAN HLTH SERV ID DOPAMINE-D2 RECEPTOR GENE; CROSS-FOSTERING ANALYSIS; INHERITANCE; HETEROGENEITY; ASSOCIATION; RELIABILITY AB This family and small community-based study reports the occurrence of alcoholism and co-occurring substance abuse in Southern Cheyenne Indians living in western Oklahoma. Sociocultural factors complicate operationalization of clinical data into standard (DSM-III-R) psychiatric disorder terminology; understanding sociocultural factors is essential for assessing the high rate of addictive disorders in this group. To obtain reliable and valid clinical diagnoses, data from several sources were utilized within a blind rating system: 1) SADS-L, a clinician-administered research diagnostic instrument; 2) MAST; 3) relatives; 4) medical records; 5) other official documents. The sample consisted of 69 males (45 alcoholics) and 97 females (36 alcoholics). Among clinically significant substance abusers (moderate impairment of function), 22 of 24 were alcoholics. In non-alcoholics, mean MAST scores were 8.8 (males) and 5.1 (females); in alcoholics, 32.0 (males) and 38.7 (females). Mean age of onset on heavy use of alcohol was 20.1 yrs. (males) and 22.8 (females) (p = 0.047); among all alcoholics, 86% (males) and 64% (females) had early onset (< 25 yrs. old). When data from 98 unrelated subjects were analyzed separately, similar findings were observed except that mean age of onset of heavy use of alcohol was more discrepant between males and females, viz. 20.1 versus 22.8 yrs. (p = 0.02). Among those with substance abuse disorders, early age of onset was present in all but one female. In these Cheyenne, alcoholism is usually clinically severe and early in onset; it often co-occurs with substance abuse, also early in onset. RP BROWN, GL (reprint author), NIAAA,DIV INTRAMURAL CLIN & BIOL RES,CLIN STUDIES LAB,ROCKVILLE,MD, USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 27 TC 6 Z9 6 U1 4 U2 6 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0165-005X J9 CULT MED PSYCHIAT JI Cult. Med. Psychiatr. PY 1992 VL 16 IS 4 BP 531 EP 542 PG 12 WC Anthropology; Psychiatry; Social Sciences, Biomedical SC Anthropology; Psychiatry; Biomedical Social Sciences GA LC253 UT WOS:A1992LC25300008 PM 1305531 ER PT J AU CASPI, RR CHAN, CC FUJINO, Y ODDO, S NAJAFIAN, F BAHMANYAR, S HEREMANS, H WILDER, RL WIGGERT, B AF CASPI, RR CHAN, CC FUJINO, Y ODDO, S NAJAFIAN, F BAHMANYAR, S HEREMANS, H WILDER, RL WIGGERT, B TI GENETIC-FACTORS IN SUSCEPTIBILITY AND RESISTANCE TO EXPERIMENTAL AUTOIMMUNE UVEORETINITIS SO CURRENT EYE RESEARCH LA English DT Article; Proceedings Paper CT 2ND INTERNATIONAL SYMP ON RECENT DEVELOPMENTS IN THE IMMUNOPATHOLOGY OF INTRAOCULAR INFLAMMATION CY OCT 22-25, 1991 CL ABERDEEN, SCOTLAND SP NATO, SANDOZ BASLE ID RETINOID-BINDING-PROTEIN; IMMUNOLOGICAL PROPERTIES; S-ANTIGEN; IMMUNODOMINANT; DETERMINANT; INDUCTION; UVEITIS; MICE; IRBP AB Experimental autoimmune uveoretinitis (EAU) can be induced in susceptible strains of rats and mice by immunization with purified retinal antigens, and serves as a model for human uveitis. Because strong HLA associations have been noted in a number of human uveitic diseases, we investigated the role of major histocompatibility complex (MHC) vs. non-MHC genes in the control of susceptibility to ocular autoimmunity, using the mouse and the rat EAU models. It was shown that EAU expression in mice requires both a susceptible MHC haplotype and a "permissive" genetic background. MHC control of susceptibility was tentatively mapped to the I-A subregion in H-2k. I-E(k) expression appeared to have an ameliorating effect on disease. Susceptible H-2 haplotypes exhibited highest disease scores on the B10 background, and disease was reduced, or even absent, on some other (nonpermissive) backgrounds. Factors which may determine "permissiveness" or "nonpermissiveness" of a particular genetic background, as studied in mice and rats, may include diverse genetic mechanisms spanning regulation of cytokines, hormones, vascular effects and the T cell repertoire. Taken together, the data suggest that, in individuals susceptible to uveitis by virtue of their MHC, the final expression of disease will be determined by the genetic background. C1 NIAMSD,BETHESDA,MD 20892. CATHOLIC UNIV LEUVEN,REGA INST,IMMUNOBIOL LAB,B-3000 LOUVAIN,BELGIUM. RP CASPI, RR (reprint author), NEI,IMMUNOL LAB,NIH BLDG 10,ROOM 10N222,BETHESDA,MD 20892, USA. NR 23 TC 19 Z9 19 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. PY 1992 VL 11 SU S BP 81 EP 86 DI 10.3109/02713689208999515 PG 6 WC Ophthalmology SC Ophthalmology GA JN104 UT WOS:A1992JN10400012 PM 1424754 ER PT J AU HARA, Y CASPI, RR WIGGERT, B CHAN, CC STREILEIN, JW AF HARA, Y CASPI, RR WIGGERT, B CHAN, CC STREILEIN, JW TI USE OF ACAID TO SUPPRESS INTERPHOTORECEPTOR RETINOID BINDING PROTEIN-INDUCED EXPERIMENTAL AUTOIMMUNE UVEITIS SO CURRENT EYE RESEARCH LA English DT Article; Proceedings Paper CT 2ND INTERNATIONAL SYMP ON RECENT DEVELOPMENTS IN THE IMMUNOPATHOLOGY OF INTRAOCULAR INFLAMMATION CY OCT 22-25, 1991 CL ABERDEEN, SCOTLAND SP NATO, SANDOZ BASLE ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MYELIN BASIC-PROTEIN; S-ANTIGEN; MONOCLONAL-ANTIBODIES; UVEORETINITIS; INHIBITION; INJECTION; TOLERANCE; CELLS; MICE AB Experimental Autoimmune Uveitis (EAU) was induced by immunization with bovine interphotoreceptor retinoid binding protein (IRBP) in B10.A mice. The experiments were performed to evaluate whether Anterior Chamber Associated Immune Deviation (ACAID) can be induced by IRBP when injected intracamerally. The results indicate that anterior chamber (AC) injection of IRBP impaired the development of IRBP-specific delayed hypersensitivity and prevented the expression of EAU following immunization with IRBP-CFA. Adoptive transfer of spleen cells obtained from mice that received IRBP into AC suppressed EAU, whether administered prior to or after the uveitogenic regimen. Most important, IRBP-specific suppressor cells from AC-IRBP treated mice when injected into IRBP-EAU mice suppressed and eliminated already established intraocular inflammation. IRBP-specific, ACAID-inducing suppressor T cells act on the efferent limb of the immune response, and represent ideal modalities for treating already established EAU. C1 UNIV MIAMI,SCH MED,DEPT MICROBIOL & IMMUNOL R138,POB 016960,MIAMI,FL 33101. UNIV MIAMI,SCH MED,DEPT OPHTHALMOL,MIAMI,FL 33101. NEI,IMMUNOL LAB,BETHESDA,MD 20892. NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. FU NEI NIH HHS [EY 05678] NR 19 TC 15 Z9 16 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PY 1992 VL 11 SU S BP 97 EP 100 DI 10.3109/02713689208999517 PG 4 WC Ophthalmology SC Ophthalmology GA JN104 UT WOS:A1992JN10400014 PM 1424755 ER PT J AU DEKOZAK, Y STIEMER, RH MIRSHAHI, M FRANK, RW DESMET, M FAURE, JP AF DEKOZAK, Y STIEMER, RH MIRSHAHI, M FRANK, RW DESMET, M FAURE, JP TI HUMORAL IMMUNE-RESPONSE AGAINST THE S-ANTIGEN TNF ALPHA COMMON EPITOPE IN RAT EAU SUPPRESSED BY THE MONOCLONAL-ANTIBODY S2D2 SO CURRENT EYE RESEARCH LA English DT Article; Proceedings Paper CT 2ND INTERNATIONAL SYMP ON RECENT DEVELOPMENTS IN THE IMMUNOPATHOLOGY OF INTRAOCULAR INFLAMMATION CY OCT 22-25, 1991 CL ABERDEEN, SCOTLAND SP NATO, SANDOZ BASLE ID TUMOR-NECROSIS-FACTOR; EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; T-CELLS; ENHANCEMENT; POTENT AB S-antigen (S-Ag)-induced experimental autoimmune uveoretinitis (EAU) in rats can be suppressed by injecting the mouse monoclonal antibody (mAb) S2D2 or a polyclonal rat anti-idiotype S2D2 (anti-Id S2D2) antibody, the internal image of the epitope of S-Ag recognized by mAb S2D2. This epitope located in amino acids 40-50 of bovine S-Ag (peptide S2), displays an homology with a sequence of human tumor necrosis factor alpha (hTNF-alpha) (peptide RRAN) which is also recognized by S2D2. (Stiemer et al., this symposium). We show that one injection of S2D2 at the time of immunization with S-Ag suppressed EAU and modulated the production of antibodies against peptides of bovine or human S-Ag containing the S2 epitope and against peptide RRAN. Immunization against anti-Id S2D2 stimulated antibody production to peptide S2 and RRAN and inhibited EAU. These data suggest that disease suppression could be related to the production of antibodies against the S-Ag/TNF-alpha common epitope. C1 UNIV HEIDELBERG,CTR MOLEC BIOL,W-6900 HEIDELBERG,GERMANY. NEI,BETHESDA,MD 20892. RP DEKOZAK, Y (reprint author), INSERM,U86,CTR RECH CORDELIERS,IMMUNOPATHOL OEIL LAB,15 RUE ECOLE MED,F-75270 PARIS 06,FRANCE. NR 19 TC 7 Z9 7 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. PY 1992 VL 11 SU S BP 119 EP 127 DI 10.3109/02713689208999521 PG 9 WC Ophthalmology SC Ophthalmology GA JN104 UT WOS:A1992JN10400018 PM 1385041 ER PT J AU KWACK, H VEECH, RL AF KWACK, H VEECH, RL TI CITRATE - ITS RELATION TO FREE MAGNESIUM-ION CONCENTRATION AND CELLULAR-ENERGY SO CURRENT TOPICS IN CELLULAR REGULATION LA English DT Review ID EQUILIBRIUM CONSTANTS; MALATE-DEHYDROGENASE; BOUND MAGNESIUM; FREE MG2+; HYDROLYSIS; LIVER; LYASE RP KWACK, H (reprint author), NIAAA,METAB & MOLEC BIOL LAB,ROCKVILLE,MD 20852, USA. NR 34 TC 12 Z9 12 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0070-2137 J9 CURR TOP CELL REGUL JI Curr. Top. Cell. Regul. PY 1992 VL 33 BP 185 EP 207 PG 23 WC Cell Biology; Physiology SC Cell Biology; Physiology GA MD696 UT WOS:A1992MD69600011 PM 1499333 ER PT J AU RODBELL, M AF RODBELL, M TI THE ROLE OF GTP-BINDING PROTEINS IN SIGNAL-TRANSDUCTION - FROM THE SUBLIMELY SIMPLE TO THE CONCEPTUALLY COMPLEX SO CURRENT TOPICS IN CELLULAR REGULATION LA English DT Review ID NUCLEOSIDE-DIPHOSPHATE KINASE; ADENYLATE-CYCLASE SYSTEM; GROWTH-FACTOR RECEPTOR; DICTYOSTELIUM-DISCOIDEUM; ACTIN POLYMERIZATION; GUANINE-NUCLEOTIDES; REGULATORY PROTEINS; HUMAN-NEUTROPHILS; PLASMA-MEMBRANES; CYCLIC-AMP RP RODBELL, M (reprint author), NIEHS,SIGNAL TRANSDUCT SECT,RES TRIANGLE PK,NC 27709, USA. NR 162 TC 54 Z9 54 U1 2 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0070-2137 J9 CURR TOP CELL REGUL JI Curr. Top. Cell. Regul. PY 1992 VL 32 BP 1 EP 47 PG 47 WC Cell Biology; Physiology SC Cell Biology; Physiology GA MD695 UT WOS:A1992MD69500001 PM 1318181 ER PT J AU MOSS, J VAUGHAN, M AF MOSS, J VAUGHAN, M TI ACTIVATION OF CHOLERA-TOXIN BY ADP-RIBOSYLATION FACTORS, 20-KDA GUANINE-NUCLEOTIDE-BINDING PROTEINS SO CURRENT TOPICS IN CELLULAR REGULATION LA English DT Review ID LABILE ENTERO-TOXIN; ESCHERICHIA-COLI ENTEROTOXINS; ADENOSINE-DIPHOSPHATE-RIBOSYLATION; MEMBRANE GM1 GANGLIOSIDE; AMINO-ACID-SEQUENCE; ROD OUTER SEGMENTS; ADENYLATE-CYCLASE; VIBRIO-CHOLERAE; RIBOSYLTRANSFERASE ACTIVITY; ENDOPLASMIC-RETICULUM RP MOSS, J (reprint author), NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892, USA. NR 159 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0070-2137 J9 CURR TOP CELL REGUL JI Curr. Top. Cell. Regul. PY 1992 VL 32 BP 49 EP 72 PG 24 WC Cell Biology; Physiology SC Cell Biology; Physiology GA MD695 UT WOS:A1992MD69500002 PM 1600746 ER PT J AU LEE, AWM AF LEE, AWM TI SIGNAL-TRANSDUCTION BY THE COLONY-STIMULATING FACTOR-I RECEPTOR - COMPARISON TO OTHER RECEPTOR TYROSINE KINASES SO CURRENT TOPICS IN CELLULAR REGULATION LA English DT Review ID EPIDERMAL GROWTH-FACTOR; FACTOR-I RECEPTOR; HUMAN INSULIN-RECEPTOR; PHOSPHOLIPASE-C-GAMMA; FMS PROTO-ONCOGENE; FELINE SARCOMA-VIRUS; MACROPHAGE CELL-LINE; ATP-BINDING-SITE; HUMAN CARCINOMA-CELLS; FACTOR EGF RECEPTOR RP LEE, AWM (reprint author), NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892, USA. NR 512 TC 10 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0070-2137 J9 CURR TOP CELL REGUL JI Curr. Top. Cell. Regul. PY 1992 VL 32 BP 73 EP 181 PG 109 WC Cell Biology; Physiology SC Cell Biology; Physiology GA MD695 UT WOS:A1992MD69500003 PM 1318184 ER PT J AU SPANGRUDE, GJ AF SPANGRUDE, GJ TI THE PRESPLEEN COLONY-FORMING UNIT ASSAY - MEASUREMENT OF SPLEEN COLONY-FORMING UNIT REGENERATION SO CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID HEMATOPOIETIC STEM-CELLS; CFU-S; MULTIPARAMETER ANALYSIS; LIMITING-DILUTION; MARROW; INVITRO; MOUSE; 5-FLUOROURACIL; ORGANIZATION; PURIFICATION RP SPANGRUDE, GJ (reprint author), NIAID,ROCKY MT LABS,PERSISTENT DIS LAB,HAMILTON,MT 59840, USA. NR 33 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0070-217X J9 CURR TOP MICROBIOL JI Curr. Top. Microbiol. Immunol. PY 1992 VL 177 BP 31 EP 39 PG 9 WC Immunology; Microbiology SC Immunology; Microbiology GA JD124 UT WOS:A1992JD12400003 PM 1638871 ER PT J AU SERVENTI, IM MOSS, J VAUGHAN, M AF SERVENTI, IM MOSS, J VAUGHAN, M TI ENHANCEMENT OF CHOLERA TOXIN-CATALYZED ADP-RIBOSYLATION BY GUANINE NUCLEOTIDE-BINDING PROTEINS SO CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID LABILE ENTERO-TOXIN; AMINO-ACID-SEQUENCE; ROD OUTER SEGMENTS; ADENOSINE-DIPHOSPHATE-RIBOSYLATION; NICOTINAMIDE ADENINE-DINUCLEOTIDE; ESCHERICHIA-COLI ENTEROTOXINS; ADENYLATE-CYCLASE; ALPHA-SUBUNIT; RIBOSYLTRANSFERASE ACTIVITY; VIBRIO-CHOLERAE RP SERVENTI, IM (reprint author), NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892, USA. NR 152 TC 26 Z9 26 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0070-217X J9 CURR TOP MICROBIOL JI Curr. Top. Microbiol. Immunol. PY 1992 VL 175 BP 43 EP 67 PG 25 WC Immunology; Microbiology SC Immunology; Microbiology GA JD322 UT WOS:A1992JD32200003 PM 1321019 ER PT J AU MOSS, B AF MOSS, B TI POXVIRUS EXPRESSION VECTORS SO CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID RECOMBINANT VACCINIA VIRUS; DOMINANT SELECTABLE MARKER; PLAQUE SIZE PHENOTYPE; RNA-POLYMERASE; FOREIGN GENES; TRANSCRIPTION TERMINATION; NUCLEOTIDE-SEQUENCE; PROTECTIVE IMMUNITY; ESCHERICHIA-COLI; MAMMALIAN-CELLS RP MOSS, B (reprint author), NIAID,VIRAL DIS LAB,BETHESDA,MD 20892, USA. NR 64 TC 18 Z9 18 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0070-217X J9 CURR TOP MICROBIOL JI Curr. Top. Microbiol. Immunol. PY 1992 VL 158 BP 25 EP 38 PG 14 WC Immunology; Microbiology SC Immunology; Microbiology GA JB197 UT WOS:A1992JB19700003 PM 1582244 ER PT J AU MOTOKURA, T YI, HF KRONENBERG, HM MCBRIDE, OW ARNOLD, A AF MOTOKURA, T YI, HF KRONENBERG, HM MCBRIDE, OW ARNOLD, A TI ASSIGNMENT OF THE HUMAN CYCLIN-D3 GENE (CCND3) TO CHROMOSOME 6P-]Q13 SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID CANDIDATE ONCOGENE; CELL; RETINOBLASTOMAS; ABNORMALITIES; LYMPHOMA; BCL-1 AB The PRAD1/cyclin D1 gene (CCND 1), a member of the D-type cyclin gene family, has been implicated as a protooncogene in parathyroid, lymphoid, and mammary tumors. We cloned and mapped another member of this family, the human cyclin D3 gene (CCND3), to chromosome 6p --> q13 using human x rodent hybrids. This assignment raises the hypothesis that cyclin D3 may be involved in the pathogenesis of human neoplasms with abnormalities of chromosome 6. C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,WELLMAN 5,FRUIT ST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NCI,BIOCHEM LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA55909]; NIDDK NIH HHS [DK11794] NR 16 TC 13 Z9 13 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1992 VL 61 IS 1 BP 5 EP 7 DI 10.1159/000133359 PG 3 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA JL517 UT WOS:A1992JL51700002 PM 1387066 ER PT J AU MITCHELL, A BALE, AE LEE, BJ HATFIELD, D HARLEY, H RUNDLE, SA FAN, YS FUKUSHIMA, Y SHOWS, TB MCBRIDE, OW AF MITCHELL, A BALE, AE LEE, BJ HATFIELD, D HARLEY, H RUNDLE, SA FAN, YS FUKUSHIMA, Y SHOWS, TB MCBRIDE, OW TI REGIONAL LOCALIZATION OF THE SELENOCYSTEINE TRANSFER-RNA GENE (TRSP) ON HUMAN CHROMOSOME-19 SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID MYOTONIC-DYSTROPHY GENE; INSITU HYBRIDIZATION; MALIGNANT HYPERTHERMIA; LINKAGE ANALYSIS; HUMAN GENOME; LONG-ARM; MAP; LOCUS; IDENTIFICATION; POLYMORPHISMS AB The human selenocysteine tRNA gene (TRSP)-has been localized on chromosome 19q13.2 --> q13.3 by in situ hybridization and ordered with respect to other genes and anonymous DNA markers in this region by linkage analysis in the forty CEPH pedigrees. These loci span only 10 cM in males and about 30 cM in females. The order of the loci is cen ... D19S7-D19S9-D19S47-CYP2A-CYP2F1-APOC2-(TRSP, CKM). CYP2B flanks the CYP2A and CYP2F1 loci, but it cannot be determined whether it is proximal or distal to the other two cytochrome P450 loci with respect to the centromere. C1 NCI,BIOCHEM LAB,BLDG 37,ROOM 4D25,BETHESDA,MD 20892. NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. UNIV WALES COLL MED,INST MED GENET,CARDIFF CF4 4XN,S GLAM,WALES. NEW YORK STATE DEPT HLTH,ROSWELL PK MEM INST,DEPT HUMAN GENET,BUFFALO,NY 14263. FU NHGRI NIH HHS [HG00333]; NICHD NIH HHS [HD05196] NR 27 TC 7 Z9 7 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1992 VL 61 IS 2 BP 117 EP 120 DI 10.1159/000133385 PG 4 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA JU352 UT WOS:A1992JU35200010 PM 1395717 ER PT J AU PLAETKE, R WEBER, J WOOD, S DEAN, M JEFFREYS, AJ WEIFFENBACH, B VERGNAUD, G VOGELSTEIN, B WHITE, R AF PLAETKE, R WEBER, J WOOD, S DEAN, M JEFFREYS, AJ WEIFFENBACH, B VERGNAUD, G VOGELSTEIN, B WHITE, R TI REPORT OF THE 2ND INTERNATIONAL WORKSHOP ON HUMAN CHROMOSOME-5 MAPPING - CONSENSUS GENETIC-MAP SO CYTOGENETICS AND CELL GENETICS LA English DT Editorial Material ID IDENTIFICATION; LINKAGE; REGIONS C1 MARSHFIELD MED RES FDN,MARSHFIELD,WI. UNIV BRITISH COLUMBIA,DEPT MED GENET,VANCOUVER V6T 1W5,BC,CANADA. NCI,FREDERICK CANC RES FACIL,FREDERICK,MD 21701. UNIV LEICESTER,DEPT GENET,LEICESTER LE1 7RH,ENGLAND. COLLABORAT RES INC,WALTHAM,MA. CTR ETUD BOUCHET,VERT LE PETIT,FRANCE. JOHNS HOPKINS UNIV HOSP,CTR ONCOL,MOLEC GENET LAB,BALTIMORE,MD 21205. UNIV UTAH,HOWARD HUGHES MED INST,SALT LAKE CITY,UT 84112. RP PLAETKE, R (reprint author), UNIV UTAH,DEPT HUMAN GENET,SALT LAKE CITY,UT 84112, USA. RI Vergnaud, Gilles/P-1304-2015 OI Vergnaud, Gilles/0000-0003-0913-194X NR 11 TC 2 Z9 2 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1992 VL 61 IS 4 BP 237 EP 242 PG 6 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA KD807 UT WOS:A1992KD80700016 PM 1362533 ER PT J AU DIONNE, CA MODI, WS CRUMLEY, G OBRIEN, SJ SCHLESSINGER, J JAYE, M AF DIONNE, CA MODI, WS CRUMLEY, G OBRIEN, SJ SCHLESSINGER, J JAYE, M TI BEK, A RECEPTOR FOR MULTIPLE MEMBERS OF THE FIBROBLAST GROWTH-FACTOR (FGF) FAMILY, MAPS TO HUMAN-CHROMOSOME 10Q25.3-]Q26 SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID GENES; EXPRESSION; CLONING AB The gene for the fibroblast growth factor receptor BEK was assigned to human chromosome 10 by applying polymerase chain reaction techniques to DNAs from a panel of human x rodent somatic cell hybrids. The gene was further localized to 10q25.3 --> q26 by in situ hybridization. C1 NCI,FREDERICK CANC RES & DEV CTR BIOL CARCINOGENESIS DEV PROGRAM,FREDERICK,MD 21701. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. NYU MED CTR,NEW YORK,NY 10016. RP DIONNE, CA (reprint author), RHONE POULENC RORER,CENT RES,680 ALLENDALE RD,KING OF PRUSSIA,PA 19406, USA. NR 15 TC 17 Z9 18 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1992 VL 60 IS 1 BP 34 EP 36 DI 10.1159/000133290 PG 3 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA HT612 UT WOS:A1992HT61200010 PM 1582255 ER PT J AU KASTNER, DL PRAS, E AKSENTIJEVICH, I HELLING, S GRUBERG, L PROSEN, L DEAN, M PRAS, M AF KASTNER, DL PRAS, E AKSENTIJEVICH, I HELLING, S GRUBERG, L PROSEN, L DEAN, M PRAS, M TI LOCALIZATION OF THE GENE CAUSING FAMILIAL MEDITERRANEAN FEVER ON THE SHORT ARM OF CHROMOSOME-16 SO CYTOGENETICS AND CELL GENETICS LA English DT Meeting Abstract C1 NIAMSD,ARTHRITIS & RHEUMATISM BRANCH,BETHESDA,MD 20892. CHAIM SHEBA MED CTR,HELLER INST MED RES,IL-52621 TEL HASHOMER,ISRAEL. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1992 VL 60 IS 3-4 BP 172 EP 172 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA JK230 UT WOS:A1992JK23000014 ER PT J AU MACCLUER, JW CHAKRAVARTI, A COX, DR BISHOP, DT BALE, SJ SKOLNICK, MH AF MACCLUER, JW CHAKRAVARTI, A COX, DR BISHOP, DT BALE, SJ SKOLNICK, MH TI GENETIC-ANALYSIS WORKSHOP-7 - ISSUES IN GENE-MAPPING AND DETECTION OF MAJOR GENES - PREFACE SO CYTOGENETICS AND CELL GENETICS LA English DT Editorial Material C1 UNIV PITTSBURGH,DEPT HUMAN GENET,PITTSBURGH,PA 15261. UNIV CALIF SAN FRANCISCO,DEPT PSYCHIAT,SAN FRANCISCO,CA 94143. IMPERIAL CANC RES FUND,GENET EPIDEMIOL LAB,LEEDS LS2 9L4,ENGLAND. NATL INST ARTHRITIS MUSCULOSKELETAL & SKIN DIS,BETHESDA,MD. UNIV UTAH,SALT LAKE CITY,UT 84108. RP MACCLUER, JW (reprint author), SW FDN BIOMED RES,DEPT GENET,POB 28147,SAN ANTONIO,TX 78228, USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1992 VL 59 IS 2-3 BP 71 EP 71 PG 1 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA HF049 UT WOS:A1992HF04900001 ER PT J AU GOLDIN, LR AF GOLDIN, LR TI MAPPING OF CHROMOSOME-21 MARKERS IN THE VENEZUELAN PEDIGREE SO CYTOGENETICS AND CELL GENETICS LA English DT Article; Proceedings Paper CT 7TH GENETIC ANALYSIS WORKSHOP : ISSUES IN GENE MAPPING AND DETECTION OF MAJOR GENES ( GAW 7 ) CY OCT 14-16, 1990 CL DAYTON, OH SP NATL INST GEN MED SCI RP GOLDIN, LR (reprint author), NIMH,CLIN NEUROGENET BRANCH,9000 ROCKVILLE PK,BLDG 10 3N218,BETHESDA,MD 20892, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1992 VL 59 IS 2-3 BP 114 EP 115 DI 10.1159/000133218 PG 2 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA HF049 UT WOS:A1992HF04900017 PM 1737473 ER PT J AU BALE, SJ GOLDSTEIN, AM TUCKER, MA AF BALE, SJ GOLDSTEIN, AM TUCKER, MA TI DESCRIPTION OF THE NATIONAL-CANCER-INSTITUTE MELANOMA FAMILIES SO CYTOGENETICS AND CELL GENETICS LA English DT Article; Proceedings Paper CT 7TH GENETIC ANALYSIS WORKSHOP : ISSUES IN GENE MAPPING AND DETECTION OF MAJOR GENES ( GAW 7 ) CY OCT 14-16, 1990 CL DAYTON, OH SP NATL INST GEN MED SCI ID CUTANEOUS MALIGNANT-MELANOMA; DYSPLASTIC NEVUS SYNDROME; PRECURSOR LESIONS C1 NCI,FAMILY STUDIES SECT,BETHESDA,MD 20892. RI Tucker, Margaret/B-4297-2015 NR 9 TC 5 Z9 5 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1992 VL 59 IS 2-3 BP 159 EP 160 DI 10.1159/000133231 PG 2 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA HF049 UT WOS:A1992HF04900030 PM 1737486 ER PT J AU AMOS, CI MURIGANDE, C AF AMOS, CI MURIGANDE, C TI PRELIMINARY EVALUATION OF LINKAGE BETWEEN CHROMOSOME-LP MARKERS AND NEVUS DENSITIES IN THE UTAH DATA SO CYTOGENETICS AND CELL GENETICS LA English DT Article; Proceedings Paper CT 7TH GENETIC ANALYSIS WORKSHOP : ISSUES IN GENE MAPPING AND DETECTION OF MAJOR GENES ( GAW 7 ) CY OCT 14-16, 1990 CL DAYTON, OH SP NATL INST GEN MED SCI ID MELANOMA; LOCUS C1 HOWARD UNIV,CTR CANC,DEPT BIOSTAT & EPIDEMIOL,WASHINGTON,DC 20060. RP AMOS, CI (reprint author), NCI,FAMILY STUDIES SECT,EEB,6130 EXECUT BLVD 439,BETHESDA,MD 20892, USA. FU NCRR NIH HHS [RR03655] NR 5 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1992 VL 59 IS 2-3 BP 173 EP 175 DI 10.1159/000133236 PG 3 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA HF049 UT WOS:A1992HF04900035 PM 1737491 ER PT J AU DEMENAIS, FM MARTINEZ, MM LAING, AE AF DEMENAIS, FM MARTINEZ, MM LAING, AE TI REGRESSIVE LOGISTIC-MODELS IN LINKAGE ANALYSIS OF THE CUTANEOUS MALIGNANT MELANOMA-DYSPLASTIC NEVUS SYNDROME SO CYTOGENETICS AND CELL GENETICS LA English DT Article; Proceedings Paper CT 7TH GENETIC ANALYSIS WORKSHOP : ISSUES IN GENE MAPPING AND DETECTION OF MAJOR GENES ( GAW 7 ) CY OCT 14-16, 1990 CL DAYTON, OH SP NATL INST GEN MED SCI C1 NIMH,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. RP DEMENAIS, FM (reprint author), HOWARD UNIV,CTR CANC,DIV BIOSTAT,2041 GEORGIA AVE NW,WASHINGTON,DC 20060, USA. RI Demenais, Florence/G-3298-2013; Martinez, Maria/B-3111-2013 OI Demenais, Florence/0000-0001-8361-0936; Martinez, Maria/0000-0003-2180-4537 FU NIGMS NIH HHS [GM41885] NR 10 TC 0 Z9 0 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1992 VL 59 IS 2-3 BP 191 EP 193 DI 10.1159/000133242 PG 3 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA HF049 UT WOS:A1992HF04900041 PM 1737497 ER PT J AU GOLDSTEIN, AM BALE, SJ TUCKER, MA AF GOLDSTEIN, AM BALE, SJ TUCKER, MA TI LINKAGE ANALYSIS OF MELANOMA ALONE AND CHROMOSOME-1P MARKERS PND, D1S47, AND LMYC SO CYTOGENETICS AND CELL GENETICS LA English DT Article; Proceedings Paper CT 7TH GENETIC ANALYSIS WORKSHOP : ISSUES IN GENE MAPPING AND DETECTION OF MAJOR GENES ( GAW 7 ) CY OCT 14-16, 1990 CL DAYTON, OH SP NATL INST GEN MED SCI RP GOLDSTEIN, AM (reprint author), NCI,FAMILY STUDIES SECT,EEB,EXECUT PLAZA N 439,BETHESDA,MD 20892, USA. RI Tucker, Margaret/B-4297-2015 NR 7 TC 4 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1992 VL 59 IS 2-3 BP 203 EP 205 DI 10.1159/000133246 PG 3 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA HF049 UT WOS:A1992HF04900045 PM 1737501 ER PT J AU DOHERTY, GM JENSEN, JC BURESH, CM NORTON, JA AF DOHERTY, GM JENSEN, JC BURESH, CM NORTON, JA TI HORMONAL-REGULATION OF INFLAMMATORY CELL CYTOKINE TRANSCRIPT AND BIOACTIVITY PRODUCTION IN RESPONSE TO ENDOTOXIN SO CYTOKINE LA English DT Article DE ACTH; HYDROCORTISONE; IL-1; IL-6; TNF ID TUMOR-NECROSIS-FACTOR; PITUITARY-ADRENAL AXIS; GENE-EXPRESSION; CYCLIC-AMP; INTERLEUKIN-1; LIPOPOLYSACCHARIDE; CACHECTIN; BEARING; RELEASE; INVIVO C1 NCI,SURG BRANCH,SURG METAB SECT,BLDG 10,ROOM 2B07,BETHESDA,MD 20892. NR 40 TC 24 Z9 24 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4666 J9 CYTOKINE JI Cytokine PD JAN PY 1992 VL 4 IS 1 BP 55 EP 62 DI 10.1016/1043-4666(92)90037-R PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA HG579 UT WOS:A1992HG57900010 PM 1319763 ER PT J AU CARTER, PH RESTORUIZ, S WASHINGTON, GC ETHRIDGE, S PALINI, A VOGT, R WAXDAL, M FLEISHER, T NOGUCHI, PD MARTI, GE AF CARTER, PH RESTORUIZ, S WASHINGTON, GC ETHRIDGE, S PALINI, A VOGT, R WAXDAL, M FLEISHER, T NOGUCHI, PD MARTI, GE TI FLOW CYTOMETRIC ANALYSIS OF WHOLE-BLOOD LYSIS, 3 ANTICOAGULANTS, AND 5 CELL PREPARATIONS SO CYTOMETRY LA English DT Article DE ETHYLENEDIAMINETETRACETIC ACID (EDTA); HEPARIN; ACD; ACID CITRATE DEXTROSE; IMMUNOPHENOTYPING; CELL VIABILITY ID LYMPHOCYTE AB We studied the effects of anticoagulants and cell preparation methods on lymphocyte forward-angle scatter (FSC), autofluorescence, and immunofluorescent staining for CD45, CD14, and CD13. Blood samples collected in ethylenediaminetetraacetic acid (EDTA), heparin, and acid citrate dextrose (ACD) were processed by using conventional Hypaque-Ficoll (HF) separation and four whole blood (WB) lysis techniques: Immuno-lyse, Q-Prep, FACS Lyse, and Gen Trak Lysis. Lymphocytes prepared by using three of the four whole blood methods gave FCS values comparable to those isolated by HF, while one method (FACS Lyse) gave consistently lower values. Autofluorescence values were comparable by all methods except Immuno-lyse, which showed consistently higher values in blood stored for 24 h with any anticoagulant. Immunofluorescent values for CD45-stained cells were quite consistent across all methods, and among the whole blood methods, FACS Lyse and Q-Prep uniformly gave the highest purity of CD45-positive cells in the lymphocyte light scatter gates. Additionally, propidium iodide (PI) analyses of CD45-stained whole blood, and analyzed without lysis, confirmed that ACD and heparin were superior to EDTA for maintaining viable leucocytes overnight. Future studies should focus on other commonly used reagents, a wide variety of abnormal samples, and cell viability. C1 CTR DIS CONTROL,DIV ENVIRONM HLTH LAB SCI,ATLANTA,GA 30333. FAST SYST INC,GAITHERSBURG,MD 20877. NIH,CC,CPD,CLIN IMMUNOL SERV,BETHESDA,MD 20892. RP CARTER, PH (reprint author), US FDA,CTR BIOL RES & EVALUAT,DIV BIOCHEM & BIOPHYS,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 8 TC 48 Z9 48 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 0196-4763 J9 CYTOMETRY JI Cytometry PY 1992 VL 13 IS 1 BP 68 EP 74 DI 10.1002/cyto.990130111 PG 7 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GX311 UT WOS:A1992GX31100009 PM 1372204 ER PT J AU GARRISON, HH HERMAN, SS LIPTON, JA AF GARRISON, HH HERMAN, SS LIPTON, JA TI INTERNATIONAL DISTRIBUTION OF DENTAL MATERIALS PUBLICATIONS AND PATENTS SO DENTAL MATERIALS LA English DT Article AB International patterns of research and development in the field of restorative dental materials were examined with data on publications (1981-85) and patents (1979-88). It was found that United States-based authors produced approximately one-half of all dental materials journal articles published worldwide, while US inventors had nearly the same share of the US dental materials patents. During the periods studied, the share of US patents in dental materials awarded to US inventors declined, while the share of US patients awarded to Japanese inventors rose. The role of the United States in research (as measured by journal articles) remained stable. Nations differed in the degree to which their researchers specialized in particular research areas. US-based authors and inventors were relatively over-represented in prosthetic materials and under-represented in dental cements, an area in which the British and the Japanese concentrated more of their activity. There was some, but not complete, agreement in the patterns of national specialization as indexed by patent and publication data. When dental materials data were compared with data for broader fields of science and technology, important differences were found. For publications, US-based authors displayed greater dominance in dental materials than in the fields of dentistry, chemistry, and materials science. US-based inventors' share of US dental materials patents was smaller than their share of all US patents. These analyses demonstrated that it was possible to use indicators derived from publication and patent data files to conduct insightful studies of a discrete specialty of science and technology. C1 PHILADELPHIA ASSOC CLIN TRIALS,ST DAVIDS,PA. NIDR,BETHESDA,MD 20892. RP GARRISON, HH (reprint author), ASPEN SYST CORP,DIV APPL MANAGEMENT SCI,962 WAYNE AVE,SILVER SPRING,MD 20910, USA. OI Garrison, Howard/0000-0001-9455-3527 FU PHS HHS [NIDR 263-87-C-0269] NR 14 TC 0 Z9 0 U1 1 U2 3 PU ACAD DENTAL MATERIALS PI DALLAS PA BAYLOR COLLEGE DENTISTRY, 3302 GASTON AVE, DALLAS, TX 75266-0677 SN 0109-5641 J9 DENT MATER JI Dent. Mater. PD JAN PY 1992 VL 8 IS 1 BP 42 EP 48 DI 10.1016/0109-5641(92)90052-E PG 7 WC Dentistry, Oral Surgery & Medicine; Materials Science, Biomaterials SC Dentistry, Oral Surgery & Medicine; Materials Science GA HL975 UT WOS:A1992HL97500009 PM 1521683 ER PT J AU MACKINNONLEWIS, C LAMB, ME ARBUCKLE, B BARADARAN, LP VOLLING, BL AF MACKINNONLEWIS, C LAMB, ME ARBUCKLE, B BARADARAN, LP VOLLING, BL TI THE RELATIONSHIP BETWEEN BIASED MATERNAL AND FILIAL ATTRIBUTIONS AND THE AGGRESSIVENESS OF THEIR INTERACTIONS SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID SCHOOL-AGED CHILDREN; SOCIAL COMPETENCE; BEHAVIOR PROBLEMS; DEPRESSION; PERCEPTIONS; MALADJUSTMENT; FAMILIES AB This study examined the relation between maternal and filial attributions and the aggressiveness of their interactions. We also examined whether or not certain setting conditions (e.g., maternal and child depression, maternal and child negative life events, marital conflict, socioeconomic status) predispose some mothers and children to make negative attributions and interact coercively. One hundred four mothers and sons (age 7-9 years) from married and divorced families participated. They completed questionnaire and interview data and were observed while participating in two gamelike tasks (e.g., Trouble, Etch-a-Sketch). Both maternal and child attributions were significantly related to their coercive interactions. The most aggressive dyads were those in which both mothers and sons perceived hostile intent in the other. The relations between attributions and coercive interactions were found to be moderated by marital conflict, and maternal education, such that the association between attributions and coercive behavior, was stronger when marital conflict was low and the mothers were better educated. C1 NICHHD,BETHESDA,MD 20892. EARL & LORAINE MILLER CHILDRENS HOSP,LONG BEACH,CA 90801. RP MACKINNONLEWIS, C (reprint author), UNIV N CAROLINA,DEPT CHILD DEV & FAMILY RELAT,FAMILY RES CTR,GREENSBORO,NC 27412, USA. NR 51 TC 57 Z9 57 U1 2 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PY 1992 VL 4 IS 3 BP 403 EP 415 DI 10.1017/S0954579400000869 PG 13 WC Psychology, Developmental SC Psychology GA JY061 UT WOS:A1992JY06100005 ER PT J AU COHN, DA COWAN, PA COWAN, CP PEARSON, J AF COHN, DA COWAN, PA COWAN, CP PEARSON, J TI MOTHERS AND FATHERS WORKING MODELS OF CHILDHOOD ATTACHMENT RELATIONSHIPS, PARENTING STYLES, AND CHILD-BEHAVIOR SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID DEVELOPMENTAL PSYCHOPATHOLOGY AB This study addresses the question of whether or not parents' working models of childhood attachments constitute a risk factor for difficulties in current parent-child relations. In a sample of 27 families and their preschool-aged children, mother-child and father-child dyads were observed in separate laboratory play sessions from which ratings of parents' and children's behavior were collected. Working models of attachment were assessed using the Adult Attachment Interview (George, Kaplan, & Main, 1984). Results showed that parents classified as insecure were less warm and provided less structure in interactions with their children than did parents classified as secure. Children of insecure parents were less warm toward their parents than were children of secure parents. Analyses of parents' joint attachment classification showed that insecure women married to insecure men were less warm and provided less structure with their children than did mothers in either the insecure-secure or secure-secure dyads. These findings suggest that, in two-parent families, an insecure working model may be a risk factor for less competent parenting but that the risk is more pronounced when both parents have insecure working models of attachment. C1 UNIV CALIF BERKELEY,BERKELEY,CA 94720. NIMH,BETHESDA,MD 20892. RP COHN, DA (reprint author), UNIV VIRGINIA,DEPT PSYCHOL,GILMER HALL,CHARLOTTESVILLE,VA 22903, USA. NR 47 TC 96 Z9 100 U1 5 U2 33 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PY 1992 VL 4 IS 3 BP 417 EP 431 DI 10.1017/S0954579400000870 PG 15 WC Psychology, Developmental SC Psychology GA JY061 UT WOS:A1992JY06100006 ER PT B AU BACHEVALIER, J AF BACHEVALIER, J BE GUNNAR, MR NELSON, CA TI CORTICAL VERSUS LIMBIC IMMATURITY - RELATIONSHIP TO INFANTILE AMNESIA SO DEVELOPMENTAL BEHAVIORAL NEUROSCIENCE SE MINNESOTA SYMPOSIA ON CHILD PSYCHOLOGY LA English DT Proceedings Paper CT 24TH MINNESOTA SYMP ON CHILD PSYCHOLOGY : DEVELOPMENTAL BEHAVIORAL NEUROSCIENCE CY OCT 19-21, 1989 CL UNIV MINNESOTA, MINNEAPOLIS, MN SP UNIV MINNESOTA, INST CHILD DEV, GEN MILLS FDN, NICHHD HO UNIV MINNESOTA ID ANTERIOR COMMUNICATING ARTERY; MEDIAL THALAMIC LESIONS; VISUAL RECOGNITION; SEX-DIFFERENCES; RHESUS-MONKEY; HIPPOCAMPAL-FORMATION; INTERTRIAL INTERVALS; MEDIODORSAL NUCLEUS; ALZHEIMERS-DISEASE; BASAL FOREBRAIN RP BACHEVALIER, J (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 0 TC 23 Z9 23 U1 2 U2 17 PU LAWRENCE ERLBAUM ASSOC PUBL PI HILLSDALE PA HILLSDALE BN 0-8058-0977-5 J9 MINN SYM CHILD PSYCH PY 1992 VL 24 BP 129 EP 153 PG 25 WC Psychology, Developmental SC Psychology GA BU78P UT WOS:A1992BU78P00005 ER PT J AU FUCHTBAUER, EM WESTPHAL, H AF FUCHTBAUER, EM WESTPHAL, H TI MYOD AND MYOGENIN ARE COEXPRESSED IN REGENERATING SKELETAL-MUSCLE OF THE MOUSE SO DEVELOPMENTAL DYNAMICS LA English DT Article DE MYOD1; MYOGENIN; MUSCLE REGENERATION; MUSCLE GRAFT; GENE EXPRESSION ID FIBROBLASTS; FAMILY; MYOBLASTS; GENE; EXPRESSION; ACTIVATION; PROTEINS; HOMOLOGY; REGION; MEMBER AB The differential expression of genes triggering myogenesis might cause or reflect differences among myoblasts. Little is known about the presence of MyoD1 and myogenin during the process of regeneration. We therefore examined the expression of MyoD1 and myogenin in muscle regeneration after grafting. Immunostaining of regenerating skeletal muscle of the mouse revealed the presence of both MyoD1 and myogenin. In mononucleated cells the proteins were not detected until shortly before fusion into myotubes. They persisted in the nuclei of regenerated muscle fibers for at least 2 weeks. MyoD1 and myogenin were not detected in nonregenerating control muscle. C1 NICHHD,MAMMALIAN GENES & DEV LAB,BETHESDA,MD 20892. NR 27 TC 127 Z9 130 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 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD JAN PY 1992 VL 193 IS 1 BP 34 EP 39 PG 6 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA HA769 UT WOS:A1992HA76900004 PM 1311614 ER PT J AU GADE, A BOHR, V BJERRUM, J UDESEN, H MORTENSEN, EL AF GADE, A BOHR, V BJERRUM, J UDESEN, H MORTENSEN, EL TI NEUROPSYCHOLOGICAL SEQUELAE IN 91 CASES OF PNEUMOCOCCAL MENINGITIS SO DEVELOPMENTAL NEUROPSYCHOLOGY LA English DT Article ID BACTERIAL-MENINGITIS; INFLUENZAE MENINGITIS; IMPACT AB During the years 1966 to 1976, 164 children and adults with pneumococcal meningitis were admitted to our hospital. By 1980, 91 of the 111 survivors were assessed with neuropsychological tests to detect cognitive deficits. The 58 adults (age range 18 to 83 years) were divided into groups with and without alternative etiologic factors (mainly head trauma with skull fracture) and compared separately with 141 normal controls. In addition to group comparisons, we made individual assessments of impairment in adults by comparing the observed data with those predicted from regression analysis. The data from 33 children were evaluated without control. In group comparisons, a deficit in the adult group was found in visuomotor speed tests. Individual assessment revealed unequivocal cognitive impairment in three patients with meningitis as the only etiologic factor. Our results indicate that detectable and sometimes serious cognitive impairment does occur in survivors from pneumococcal meningitis, although it is probably infrequent. C1 KOMMUNE HOSP COPENHAGEN,INST PSYKOL,DK-1399 COPENHAGEN,DENMARK. UNIV COPENHAGEN,PSYCHOL LAB,DK-1168 COPENHAGEN,DENMARK. RIGSHOSP,DEPT INFECT DIS,DK-2100 COPENHAGEN,DENMARK. NCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RP GADE, A (reprint author), RIGSHOSP,DEPT NEUROL,9 BLEGDAMSVEJ,DK-2100 COPENHAGEN,DENMARK. NR 32 TC 0 Z9 0 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 SN 8756-5641 J9 DEV NEUROPSYCHOL JI Dev. Neuropsychol. PY 1992 VL 8 IS 4 BP 447 EP 457 PG 11 WC Psychology, Developmental; Psychology; Psychology, Experimental SC Psychology GA KE528 UT WOS:A1992KE52800007 ER PT J AU ZAHNWAXLER, C RADKEYARROW, M WAGNER, E CHAPMAN, M AF ZAHNWAXLER, C RADKEYARROW, M WAGNER, E CHAPMAN, M TI DEVELOPMENT OF CONCERN FOR OTHERS SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID INFANTS RESPONSES; EXPRESSIONS; DISTRESS; MOTHERS; EMPATHY; PERSPECTIVE; IMITATION; CHILDREN; EMOTIONS; FAMILY AB The development of prosocial and reparative behaviors was investigated by examining children's responses to distresses they caused and those they witnessed in others during the 2nd year of life. Prosocial behaviors (help, sharing, provision of comfort) emerged between the ages of 1 and 2, increasing in frequency and variety over this time period. These behaviors were linked to expressions of concern as well as efforts to understand and experience the other's plight. Children's reparative behaviors after they had caused distress also increased with age. Age changes in these early signs of moral development were accompanied by social-cognitive changes in self-recognition. In assessments at age 2, children were most responsive to distress in their mothers but also showed some sensitivity toward unfamiliar persons. C1 UNIV BRITISH COLUMBIA,VANCOUVER V6T 1W5,BC,CANADA. RP ZAHNWAXLER, C (reprint author), NIMH,DEV PSYCHOL LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 60 TC 447 Z9 453 U1 18 U2 104 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD JAN PY 1992 VL 28 IS 1 BP 126 EP 136 DI 10.1037/0012-1649.28.1.126 PG 11 WC Psychology, Developmental SC Psychology GA HC278 UT WOS:A1992HC27800016 ER PT J AU GREINER, TC LINDER, J AF GREINER, TC LINDER, J TI POLYMERASE CHAIN-REACTION - USES AND POTENTIAL APPLICATIONS IN CYTOLOGY SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article RP GREINER, TC (reprint author), NCI,PATHOL LAB,BLDG 10,RM 2N113,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 6 Z9 6 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 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PY 1992 VL 8 IS 1 BP 61 EP 64 DI 10.1002/dc.2840080112 PG 4 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA HG468 UT WOS:A1992HG46800010 PM 1551366 ER PT J AU GREINER, TC MITROS, FA STAPLETON, J VANRYBROEK, J AF GREINER, TC MITROS, FA STAPLETON, J VANRYBROEK, J TI FINE-NEEDLE ASPIRATION FINDINGS OF THE LIVER IN A CASE OF Q-FEVER SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Note DE GRANULOMA; INFLAMMATION; CYTOLOGY; BIOPSY; HEPATITIS AB This report describes the cytologic findings in Q fever involving the liver in a 59-yr-old man. The fine-needle aspiration findings are correlated with a surgical needle biopsy performed concurrently. Cytopathologists should include Q fever in their differential diagnosis of granulomatous inflammation. Ring granulomas, which can be seen in an aspiration biopsy, should suggest the diagnosis of Q fever. RP GREINER, TC (reprint author), NCI,PATHOL LAB,BLDG 10,RM 2N113,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 4 Z9 4 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 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PY 1992 VL 8 IS 2 BP 181 EP 184 DI 10.1002/dc.2840080218 PG 4 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA HQ559 UT WOS:A1992HQ55900016 PM 1568415 ER PT J AU ENGLANDER, EW WILSON, SH AF ENGLANDER, EW WILSON, SH TI THE CLONED PROMOTER OF THE HUMAN DNA BETA-POLYMERASE GENE CONTAINS A CAMP RESPONSE ELEMENT FUNCTIONAL IN HELA-CELLS SO DNA AND CELL BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR CREB; ATF CDNA CLONES; CYCLIC-AMP; BINDING-PROTEIN; PHOSPHORYLATION; N-METHYL-N'-NITRO-N-NITROSOGUANIDINE; ACTIVATION; EXPRESSION; FAMILY; FORMS AB The mammalian DNA beta-polymerase (beta-pol) gene is constitutively expressed in cultured cells as a function of growth stage and DNA replication, but is expressed in rodents in a tissue-specific fashion. As revealed by transient expression experiments with wild-type and mutated beta-pol promoter fusion genes, the cloned human beta-pol promoter is transcriptionally regulated by signals acting through the single palindromic sequence (GTGACGTCAC) known as an ATF/CRE-binding site centered at position -45 in the core promoter. Although the mere presence of the ATF/CRE palindromic sequence in a promoter does not always confer cAMP responsiveness or protein binding over and around the ATF/CRE sequence, we find that agents that increase cAMP levels (forskolin and IBMX) in HeLa cells activate the beta-pol promoter; activation also can be observed by coexpression of the protein kinase A catalytic subunit. Experiments with mutagenized beta-pol promoters indicate that the ATF/CRE-binding site mediates these effects. Thus, the ATF/CRE-binding site in the context of this TATA-less constitutive promoter is able to respond to the kinase A signal transduction pathway. RP ENGLANDER, EW (reprint author), NCI,BIOCHEM LAB,BLDG 6,ROOM 416,BETHESDA,MD 20892, USA. NR 35 TC 15 Z9 15 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD JAN-FEB PY 1992 VL 11 IS 1 BP 61 EP 69 DI 10.1089/dna.1992.11.61 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA JG481 UT WOS:A1992JG48100006 PM 1310859 ER PT J AU BOCEK, P CHRAMBACH, A AF BOCEK, P CHRAMBACH, A TI CAPILLARY ELECTROPHORESIS IN AGAROSE SOLUTIONS - EXTENSION OF SIZE SEPARATIONS TO DNA OF 12-KB IN LENGTH SO ELECTROPHORESIS LA English DT Article AB The upper limit of the size range of DNA amenable to separation in agarose solutions above their gelling temperature, using capillary zone electrophoresis apparatus, was increased to 12 kb. The plot of log(bp) vs. mobility derived from electrophoresis in 1.7% agarose solution is biphasic, exhibiting higher resolving power for DNA less than 1 kb in size than that of larger sizes. Resolving power for DNA larger than 1 kb increased when the agarose concentration was increased in the range of 1.0-2.6%. It was similar in solutions at 40-degrees-C of SeaPrep and SeaPlaque agaroses as well as in Acrylaide (trade names are those of the manufacturer). However, the resolving power of SeaPrep agarose at 25-degrees-C was inferior to that at 40-degrees-C. Concave plots of log(mobility) vs. concentration of the agarose solutions are those predicted under the assumption that the effective "equivalent radius" of the DNA molecule diminishes with increasing agarose concentration in the investigated concentration range up to 2.6%. C1 NICHHD,THEORET & PHYS BIOL LAB,MACROMOLEC ANAL SECT,BETHESDA,MD 20892. NR 8 TC 77 Z9 78 U1 0 U2 3 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 JAN-FEB PY 1992 VL 13 IS 1-2 BP 31 EP 34 DI 10.1002/elps.1150130106 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA HH060 UT WOS:A1992HH06000005 PM 1587250 ER PT J AU CHU, CS TRAPNELL, BC MURTAGH, JJ MOSS, J DALEMANS, W JALLAT, S MERCENIER, A PAVIRANI, A LECOCQ, JP CUTTING, GR GUGGINO, WB CRYSTAL, RG AF CHU, CS TRAPNELL, BC MURTAGH, JJ MOSS, J DALEMANS, W JALLAT, S MERCENIER, A PAVIRANI, A LECOCQ, JP CUTTING, GR GUGGINO, WB CRYSTAL, RG TI CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR (CFTR) GENE TRANSCRIPTS SO EMBO JOURNAL LA English DT Letter ID CELLULAR IMMUNITY; BACTERIA C1 NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892. TRANSGENE SA,STRASBOURG,FRANCE. JOHNS HOPKINS UNIV HOSP,DEPT PEDIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV HOSP,CTR MED GENET,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. RP CHU, CS (reprint author), NHLBI,PULM BRANCH,BETHESDA,MD 20892, USA. NR 7 TC 3 Z9 3 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD JAN PY 1992 VL 11 IS 1 BP 379 EP 380 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GZ966 UT WOS:A1992GZ96600043 ER EF