FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Wright, A Kawakami, Y Pavan, W AF Wright, A Kawakami, Y Pavan, W TI Mart1 is located on mouse Chromosome 19 and is excluded as a candidate for ep and ru SO MAMMALIAN GENOME LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; MELANOMA ANTIGEN GP100; MULTIPLE EPITOPES; LINES; RECOGNITION; PEPTIDES; MAPS C1 NIH,LAG BENET DIS RES,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NCI,SURG BRANCH,NATL INST HLTH,BETHESDA,MD 20892. NR 19 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD MAY PY 1997 VL 8 IS 5 BP 377 EP 378 DI 10.1007/s003359900446 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA WU065 UT WOS:A1997WU06500021 PM 9107690 ER PT J AU Hoffman, MP Zheng, C Baum, BB OConnell, BC Kleinman, HKLDB AF Hoffman, MP Zheng, C Baum, BB OConnell, BC Kleinman, HKLDB TI Identification of components in Matrigel involved in salivary gland acinar cell differentiation using an adenovirus vector with an acinar cell specific promoter luciferase reporter SO MATRIX BIOLOGY LA English DT Meeting Abstract C1 NIDR,NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD MAY PY 1997 VL 16 IS 2 BP 72 EP 72 DI 10.1016/S0945-053X(97)90087-1 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XC546 UT WOS:A1997XC54600017 ER PT J AU Kadoya, Y Nomizu, M Yamashina, S Yamada, Y AF Kadoya, Y Nomizu, M Yamashina, S Yamada, Y TI Laminin-1 G-domain peptide, RKRLQVQLSIRT, inhibits submandibular gland morphogenesis in vitro SO MATRIX BIOLOGY LA English DT Meeting Abstract C1 NIDR,DEV BIOL LAB,NIH,BETHESDA,MD 20892. KITASATO UNIV,DEPT ANAT,SAGAMIHARA,KANAGAWA 228,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD MAY PY 1997 VL 16 IS 2 BP 73 EP 74 DI 10.1016/S0945-053X(97)90090-1 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XC546 UT WOS:A1997XC54600020 ER PT J AU Malinda, KM Goldstein, AL Kleinman, HK AF Malinda, KM Goldstein, AL Kleinman, HK TI Thymosins beta(4) and alpha(1) promote migration of human umbilical vein endothelial cells SO MATRIX BIOLOGY LA English DT Meeting Abstract C1 GEORGE WASHINGTON UNIV,SCH MED & HLTH SERV,DEPT BIOCHEM & MOL BIOL,WASHINGTON,DC. NIDR,DEV BIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD MAY PY 1997 VL 16 IS 2 BP 79 EP 80 DI 10.1016/S0945-053X(97)90104-9 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XC546 UT WOS:A1997XC54600034 ER PT J AU Henter, JI Arico, M Egeler, RM Elinder, G Favara, BE Filipovich, AH Gadner, H Imashuku, S JankaSchaub, G Komp, D Ladisch, S Webb, D AF Henter, JI Arico, M Egeler, RM Elinder, G Favara, BE Filipovich, AH Gadner, H Imashuku, S JankaSchaub, G Komp, D Ladisch, S Webb, D TI HLH-94: A treatment protocol for hemophagocytic lymphohistiocytosis SO MEDICAL AND PEDIATRIC ONCOLOGY LA English DT Article ID FAMILIAL ERYTHROPHAGOCYTIC LYMPHOHISTIOCYTOSIS; BONE-MARROW TRANSPLANTATION; SOLUBLE INTERLEUKIN-2 RECEPTOR; NATURAL-KILLER ACTIVITY; MALIGNANT HISTIOCYTOSIS; INTERFERON-GAMMA; EPIPODOPHYLLOTOXIN; HYPERCYTOKINEMIA; CHEMOTHERAPY; INVOLVEMENT C1 POLICLIN SAN MATTEO,IRCCS,PEDIAT CLIN,I-27100 PAVIA,ITALY. SOPHIA CHILDRENS UNIV HOSP,ROTTERDAM,NETHERLANDS. SACHS CHILDRENS HOSP,STOCKHOLM,SWEDEN. NIH,ROCKY MT LAB,HAMILTON,MT. CHILDRENS HOSP,MED CTR,CINCINNATI,OH 45229. ST ANNA CHILDRENS HOSP,A-1090 VIENNA,AUSTRIA. KYOTO CITY INST HLTH & ENVIRONM SCI,KYOTO,JAPAN. CHILDRENS UNIV HOSP,HAMBURG,GERMANY. YALE UNIV,SCH MED,NEW HAVEN,CT. CTR CANC & TRASPLANTAT BIOL,WASHINGTON,DC. GREAT ORMOND ST HOSP CHILDREN,DEPT HEMATOL,LONDON WC1N 3JH,ENGLAND. RP Henter, JI (reprint author), KAROLINSKA HOSP,DEPT PEDIAT,S-17176 STOCKHOLM,SWEDEN. NR 42 TC 214 Z9 230 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 0098-1532 J9 MED PEDIATR ONCOL JI Med. Pediatr. Oncol. PD MAY PY 1997 VL 28 IS 5 BP 342 EP 347 DI 10.1002/(SICI)1096-911X(199705)28:5<342::AID-MPO3>3.0.CO;2-H PG 6 WC Oncology; Pediatrics SC Oncology; Pediatrics GA WQ790 UT WOS:A1997WQ79000003 PM 9121398 ER PT J AU Wolffe, AP Ura, K AF Wolffe, AP Ura, K TI Transcription of dinucleosomal templates SO METHODS-A COMPANION TO METHODS IN ENZYMOLOGY LA English DT Article ID RNA-POLYMERASE TRANSCRIBES; LINKER HISTONES B4; GENE-TRANSCRIPTION; NUCLEOSOME CORE; IN-VIVO; CHROMATIN; DNA; H1; EMBRYOS; TRANSITIONS AB Nucleosomes and the chromatin structures they assemble provide the architectural foundation for the transcription process. We describe the use of reconstituted chromatin templates assembled using purified histones and HMGs to investigate the significance of chromatin structure for transcription. Our structural assays include sucrose gradient fractionation, nucleoprotein gel analysis, micrococcal nuclease digestion, DNase I and hydroxyl radical cleavage mapping of nucleosome position, and determination of nucleosome mobility. We determine the consequences of incorporation of linker histones or HMG1 on the properties of the nucleosome and the transcription process. Our results indicate that linker histones and HMG1 can direct the positioning of core histone-DNA interactions, restrict nucleosome mobility, and repress transcription. (C) 1997 Academic Press. RP Wolffe, AP (reprint author), NICHHD,MOL EMBRYOL LAB,NIH,BLDG 18T,ROOM 101,BETHESDA,MD 20892, USA. NR 26 TC 5 Z9 5 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1046-2023 J9 METHODS JI Methods PD MAY PY 1997 VL 12 IS 1 BP 10 EP 19 DI 10.1006/meth.1997.0442 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XT379 UT WOS:A1997XT37900003 PM 9169190 ER PT J AU Pruss, D Bavykin, SG AF Pruss, D Bavykin, SG TI Chromatin studies by DNA-protein cross-linking SO METHODS-A COMPANION TO METHODS IN ENZYMOLOGY LA English DT Article ID NUCLEOSOME CORE PARTICLE; ALDEHYDIC ABASIC SITES; PRIMARY ORGANIZATION; ESCHERICHIA-COLI; HISTONE OCTAMER; STRAND CLEAVAGE; DOMAIN; MODEL; SUPERSTRUCTURE; CROSSLINKING AB Our current level of understanding of chromatin structure was to a large extent achieved with the help of DNA-protein cross-linking. The versatile inventory of cross-linking techniques allows the identification of the contacts between DNA and proteins with a single nucleotide-single amino acid precision, to detect minor components of the complex nucleoprotein systems, to reveal the interactions of the flexible protein domains with DNA, and to assay for conformational changes in the nucleosomes. (C) 1997 Academic Press. C1 NICHHD,MOL EMBRYOL LAB,NIH,BETHESDA,MD 20892. RUSSIAN ACAD SCI,VA ENGELHARDT MOL BIOL INST,MOSCOW 117984,RUSSIA. NR 66 TC 9 Z9 9 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1046-2023 J9 METHODS JI Methods PD MAY PY 1997 VL 12 IS 1 BP 36 EP 47 DI 10.1006/meth.1997.0445 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XT379 UT WOS:A1997XT37900006 PM 9169193 ER PT J AU Dimitrov, SI Wolffe, AP AF Dimitrov, SI Wolffe, AP TI Fine resolution of histones by two-dimensional polyacrylamide gel electrophoresis: Developmental implications SO METHODS-A COMPANION TO METHODS IN ENZYMOLOGY LA English DT Article ID SPERM CHROMATIN; EGG EXTRACTS; ACETYLATION; TRANSCRIPTION; B4 AB A two-dimensional electrophoresis for fine separation of histones is described in detail. The method is relatively simple and gives very reproducible results. In the first dimension the histones are separated by their charge in acid-urea gels, while in the second dimension the separation is based on both the charge and the differential affinity of histones to Triton in acid-urea-Triton gels. In this electrophoretic system, the linker histones are resolved on the gel diagonal, while the core histones are separated above the diagonal. The electrophoresis is very sensitive to charge effect, and thus it is very well suited to resolving histone-modified forms. The application of the two-dimensional electrophoresis in Xenopus developmental studies is illustrated. (C) 1997 Academic Press. C1 NICHHD,MOL EMBRYOL LAB,NIH,BETHESDA,MD 20892. RP Dimitrov, SI (reprint author), INST ALBERT BONNIOT,LAB ETUD DIFFERENCIAT & ADHERENCE CELLULAIRES,UMR CNRS UJF 5538,F-38706 LA TRONCHE,FRANCE. RI dimitrov, stefan/M-7697-2013 NR 15 TC 18 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1046-2023 J9 METHODS JI Methods PD MAY PY 1997 VL 12 IS 1 BP 57 EP 61 DI 10.1006/meth.1997.0447 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA XT379 UT WOS:A1997XT37900008 PM 9169195 ER PT J AU Gibbons, D Fogt, F Kasznica, J Holden, J Nikulasson, S AF Gibbons, D Fogt, F Kasznica, J Holden, J Nikulasson, S TI Comparison of topoisomerase II alpha and MIB-1 expression in uterine cervical squamous lesions SO MODERN PATHOLOGY LA English DT Article DE MIB-1; proliferation markers; squamous epithelial dysplasia; topoisomerase II alpha; uterine cervix ID CELL-PROLIFERATION; ANTIGEN; KI-67; DNA AB The aim of this study was to assess the role of MIB-1 in the classification of cervical:squamous lesions and to compare it with a novel proliferation marker, topoisomerase II alpha (TP II alpha). We classified 46 archival uterine cervical cases into 6 groups: normal (n = 3); human papillomavirus (n = 15); mild (n = 10), moderate (n = 7), and severe (n = 6) cervical intraepithelial neoplasia; and invasive carcinoma (n = 5). The formalin-fixed, paraffin-embedded tissue sections were stained with monoclonal antibodies to Ki-67 (MIB-1) and TP II alpha with a standard streptavidin immunohistochemical technique, with antigen retrieval to assess enzyme presence. The results were based on nuclear staining and percentage of positivity. We found that the mean percentage of positive nuclei increased from normal through increasing grades of dysplasia to its maximal level in invasive carcinoma The level of positive nuclei in the epithelium also generally increased from basal to full thickness with progression of the lesions. The correlation between the percentage of nuclei positive for both antibodies with the use of linear regression was close, with an r value of 0.85. Our conclusions were that MIB-1 is an adjunct in the classification of squamous lesions of the uterine cervix and that TP II alpha is a useful proliferation marker in this setting. C1 BOSTON UNIV,SCH MED,MALLORY INST PATHOL,DEPT PATHOL & LAB MED,BOSTON,MA 02118. NIH,BETHESDA,MD 20892. UNIV UTAH,MED CTR,DEPT PATHOL,SALT LAKE CITY,UT. NR 14 TC 27 Z9 28 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAY PY 1997 VL 10 IS 5 BP 409 EP 413 PG 5 WC Pathology SC Pathology GA WZ853 UT WOS:A1997WZ85300002 PM 9160303 ER PT J AU Balagopalakrishna, C Bhunia, AK Rifkind, JM Chatterjee, S AF Balagopalakrishna, C Bhunia, AK Rifkind, JM Chatterjee, S TI Minimally modified low density lipoproteins induce aortic smooth muscle cell proliferation via the activation of mitogen activated protein kinase SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE cell proliferation; modified low density lipoproteins; mitogen activated protein kinase; aortic smooth muscle cells AB We have investigated the effects of modifying LDL by Cu++ and various hemoglobin preparations on aortic smooth muscle cell proliferation and on the activation of mitogen activated protein kinase. We found that at very low concentrations (10 mu g/ml), LDL modified by all of the above agonists markedly stimulated cell proliferation (5-10 fold). This was accompanied by a 2-3 fold stimulation in mitogen activated protein kinase (MAPK) activity. We conclude that modification of LDL under situations that are closer to those found in vivo (i.e. hypoxic conditions), may involve the activation of MAPK as a common biochemical mechanism of action. This in turn, contributes to aortic smooth muscle cell proliferation. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,LIPID RES ATHEROSCLEROSIS UNIT,BALTIMORE,MD 21205. NIA,CELLULAR & MOL BIOL LAB,NIH,BALTIMORE,MD 21224. NR 15 TC 17 Z9 17 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD MAY PY 1997 VL 170 IS 1-2 BP 85 EP 89 DI 10.1023/A:1006840927835 PG 5 WC Cell Biology SC Cell Biology GA WV541 UT WOS:A1997WV54100010 PM 9144321 ER PT J AU Cultraro, CM Bino, T Segal, S AF Cultraro, CM Bino, T Segal, S TI Function of the c-Myc antagonist mad1 during a molecular switch from proliferation to differentiation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MURINE ERYTHROLEUKEMIA-CELLS; POST-TRANSCRIPTIONAL REGULATION; DNA-BINDING; ORNITHINE DECARBOXYLASE; ACTIVATES TRANSCRIPTION; RAS COTRANSFORMATION; OPPOSITE REGULATION; GENE-TRANSCRIPTION; ONCOGENIC ACTIVITY; REPRESSOR SIN3 AB Mad-Max heterodimers have been shown to antagonize Myc transforming activity by a mechanism requiring multiple protein-protein and protein-DNA interactions. However, the mechanism by which Mad functions in differentiation is unknown. Here, we present evidence that Mad functions by an active repression mechanism to antagonize the growth-promoting function(s) of Myc and bring about a transition from cellular proliferation to differentiation. We demonstrate that exogenously expressed c-Myc blocks inducer-mediated differentiation of murine erythroleukemia cells without disrupting the induction of endogenous Mad; rather, high levels of c-Myc prevent a heterocomplex switch from growth-promoting Myc-Max to growth-inhibitory Mad-Max. Cotransfection of a constitutive c-myc with a zinc-inducible madl results in clones expressing both genes, whereby a switch from proliferation to differentiation can be modulated. Whereas cells grown in N'N'-hexamethylene bisacetamide in the absence of zinc fail to differentiate, addition of zinc up-regulates Mad expression by severalfold and differentiation proceeds normally. Coimmunoprecipitation analysis reveals that Mad-Max complexes are in excess of Myc-Max in these cotransfectants. Moreover, we show that the Sin-binding, basic region, and leucine zipper motifs are required for Mad to function during a molecular switch from proliferation to differentiation. C1 NCI,NAVY MED ONCOL BRANCH,NIH,BETHESDA,MD 20889. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20889. NR 70 TC 64 Z9 64 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 MAY PY 1997 VL 17 IS 5 BP 2353 EP 2359 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WV199 UT WOS:A1997WV19900001 PM 9111304 ER PT J AU Lyakh, L Ghosh, P Rice, NR AF Lyakh, L Ghosh, P Rice, NR TI Expression of NFAT-family proteins in normal human T cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR NFATP; NUCLEAR FACTOR; IMMUNOSUPPRESSIVE DRUGS; GENE; ACTIVATION; INDUCTION; PROMOTER; LYMPHOCYTE; BINDING; ALPHA AB NFAT proteins constitute a family of transcription factors involved in mediating signal transduction. Using a panel of specific antisera in immunoprecipitation assays, we found that NFATp (135 kDa) is constitutively expressed in normal human T cells, while synthesis of NFATc (predominant form of 86 kDa) is induced by ionomycin treatment. NFAT4/x was very weakly expressed in unstimulated cells, and its level did not increase upon treatment with activating agents. NFAT3 protein was not observed under any conditions. Higher-molecular-weight species of NFATc (of 110 and 140 kDa) were also detected. In addition, translation of NFATc mRNA apparently initiates at two different AUG codons, giving rise to proteins that differ in size by 36 amino acids. Additional size heterogeneity of both NFATc and NFATp results from phosphorylation. In contrast to ionomycin treatment, exposure of cells to phorbol myristate acetate (PMA) plus anti-CD28 did not induce NFATc, indicating that under these conditions, interleukin-2 synthesis by these cells is apparently independent of NFATc. In DNA binding assays, both PMA plus anti-CD28 and PMA plus ionomycin resulted in nuclear NFAT. Surprisingly, the PMA-ionomycin-induced synthesis of NFATc that was detected by immunoprecipitation was not mirrored in the DNA binding assays: nearly all of the activity was due to NFATp. This is the first study of expression of all family members at the protein level in normal human T cells. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOL BIOL RETROVIRUSES SECT,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SAIC,LAB EXPT IMMUNOL,DIV BASIC SCI,FREDERICK,MD 21702. NR 45 TC 136 Z9 138 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1997 VL 17 IS 5 BP 2475 EP 2484 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WV199 UT WOS:A1997WV19900013 PM 9111316 ER PT J AU Haynes, SR Cooper, MT Pype, S Stolow, DT AF Haynes, SR Cooper, MT Pype, S Stolow, DT TI Involvement of a tissue-specific RNA recognition motif protein in Drosophila spermatogenesis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MOLECULAR-GENETIC ANALYSIS; BINDING PROTEIN; MESSENGER-RNA; CYTOPLASMIC POLYADENYLATION; TRANSLATIONAL REGULATION; MELANOGASTER; DOMAINS; ELEMENT; ENCODES; MOUSE AB RNA binding proteins mediate posttranscriptional regulation of gene expression via their roles in nuclear and cytoplasmic mRNA metabolism. Many of the proteins involved in these processes have a common RNA binding domain, the RNA recognition motif (RRM). We have characterized the Testis-specific RRM protein gene (Tsr), which plays an important role in spermatogenesis in Drosophila melanogaster. Disruption of Tsr led to a dramatic reduction in male fertility due to the production of spermatids with abnormalities in mitochondrial morphogenesis. Tar is located on the third chromosome at 87F, adjacent to the nuclear pre-mRNA binding protein gene Hrb87F. A 1.7-kb Tsr transcript was expressed exclusively in the male germ line. It encoded a protein containing two RRMs similar to those found in HRB87F as well as a unique C-terminal domain. TSR protein was located in the cytoplasm of spermatocytes and young spermatids but was absent from mature sperm. The cellular proteins expressed in premeiotic primary spermatocytes from Tsr mutant and wild-type males were assessed by two-dimensional gel electrophoresis, Lack of TSR resulted in the premature expression of a few proteins prior to meiosis; this was abolished by a transgenic copy of Tsr. These data demonstrate that TSR negatively regulated the expression of some testis proteins and, in combination with its expression pattern and subcellular localization, suggest that TSR regulates the stability or translatability of some mRNAs during spermatogenesis. RP Haynes, SR (reprint author), NICHHD,GENET MOL LAB,NIH,BLDG 6B,RM 3B331,6 CTR DR,MSC 2785,BETHESDA,MD 20892, USA. NR 58 TC 21 Z9 21 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 MAY PY 1997 VL 17 IS 5 BP 2708 EP 2715 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WV199 UT WOS:A1997WV19900038 PM 9111341 ER PT J AU Tran, HT Keen, JD Kricker, M Resnick, MA Gordenin, DA AF Tran, HT Keen, JD Kricker, M Resnick, MA Gordenin, DA TI Hypermutability of homonucleotide runs in mismatch repair and DNA polymerase proofreading yeast mutants SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SIMPLE REPETITIVE DNA; CARCINOMA CELL-LINES; SACCHAROMYCES-CEREVISIAE; MICROSATELLITE INSTABILITY; SPONTANEOUS MUTATIONS; REPLICATION ERRORS; BETA RECEPTOR; COLON-CANCER; GENE; SEQUENCES AB Homonucleotide runs in coding sequences are hot spots for frameshift mutations and potential sources of genetic changes leading to cancer in humans having a mismatch repair defect. We examined frameshift mutations in homonucleotide runs of deoxyadenosines ranging from 4 to 14 bases at the same position in the LYS2 gene of the yeast Saccharomyces cerevisiae, In the msh2 mismatch repair mutant, runs of 9 to 14 deoxyadenosines are 1,700-fold to 51,000-fold, respectively, more mutable for single nucleotide deletions than are runs of 4 deoxyadenosines. These frameshift mutations can account for up to 99% of all forward mutations inactivating the 4-kh LYS2 gene. Based on results with single and double mutations of the POL2 and MSH2 genes, both DNA polymerase epsilon proofreading and mismatch repair are efficient for short runs while only the mismatch repair system prevents frameshift mutations in runs of greater than or equal to 8 nucleotides. Therefore, coding sequences containing long homonucleotide runs are likely to be at risk for mutational inactivation in cells lacking mismatch repair capability. C1 NIEHS,GENOME STABIL SECT,GENET MOL LAB,RES TRIANGLE PK,NC 27709. ST PETERSBURG STATE UNIV,DEPT GENET,ST PETERSBURG 199034,RUSSIA. OI Gordenin, Dmitry/0000-0002-8399-1836 NR 63 TC 212 Z9 213 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 MAY PY 1997 VL 17 IS 5 BP 2859 EP 2865 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WV199 UT WOS:A1997WV19900055 PM 9111358 ER PT J AU Nesnow, S Gilmer, T Hohman, RJ Pfeifer, AMA Trump, BF Wogan, G Tennant, R AF Nesnow, S Gilmer, T Hohman, RJ Pfeifer, AMA Trump, BF Wogan, G Tennant, R TI Eleventh Aspen Cancer Conference: Mechanisms of toxicity and carcinogenesis SO MOLECULAR CARCINOGENESIS LA English DT Editorial Material C1 GLAXO WELLCOME INC, DEPT CELL BIOL, RES TRIANGLE PK, NC 27709 USA. ONCOR INC, RES & DEV, GAITHERSBURG, MD 20877 USA. NESTEC LTD, RES CTR, CH-1000 LAUSANNE 26, SWITZERLAND. UNIV MARYLAND, SCH MED, DEPT PATHOL, BALTIMORE, MD 21201 USA. MIT, DIV TOXICOL, CAMBRIDGE, MA 02139 USA. NIEHS, RES TRIANGLE PK, NC 27709 USA. RP Nesnow, S (reprint author), US EPA, BIOCHEM & PATHOBIOL BRANCH, NATL HLTH & ENVIRONM EFFECTS RES LAB, MD-68, RES TRIANGLE PK, NC 27711 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0899-1987 EI 1098-2744 J9 MOL CARCINOGEN JI Mol. Carcinog. PD MAY PY 1997 VL 19 IS 1 BP 1 EP 7 PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA XC420 UT WOS:A1997XC42000001 ER PT J AU Romach, EH Goldsworthy, TL Maronpot, RR Fox, TR AF Romach, EH Goldsworthy, TL Maronpot, RR Fox, TR TI Altered gene expression in spontaneous hepatocellular carcinomas from male B6C3F1 mice SO MOLECULAR CARCINOGENESIS LA English DT Article DE liver cancer; oncogenes; insulin-like growth factor II; cyclin D1 ID GROWTH-FACTOR-ALPHA; RAT-LIVER REGENERATION; FACTOR-II; TRANSGENIC MICE; DIFFERENTIAL EXPRESSION; CYCLIN D1; C-MYC; OVEREXPRESSION; ONCOGENES; TUMORS AB In this study, we analyzed spontaneous hepatocellular carcinomas (HCCs) from male B6C3F1 mice for alterations in the expression of the genes for c-myc, insulin-like growth factor II (IGF-II), cyclin D1, transforming growth factor-alpha (TCF-alpha), and the epidermal growth factor receptor (EGFR). These genes are all important in growth control in the rodent liver, and therefore, alterations in these genes or their products may result in unregulated growth. Northern blot analysis demonstrated an increase in expression of c-myc mRNA in five of 21 (24%) spontaneous HCCs compared with nontumor tissue. Tumors that had an increase in c-myc mRNA did not have an amplified c-myc gene. Of the HCCs analyzed, 18 of 29 (62%) showed reexpression of ICF-II RNA when compared with controls. Cyclin D1 mRNA was overexpressed in seven of 27 (26%) of the tumors analyzed relative to controls. Tumors with an increase in cyclin D1 mRNA also overexpressed the cyclin D1 protein. RNA encoding for the EGFR was decreased in 21 of 23 (91%) HCCs when compared with controls. None of the 29 liver tumors analyzed for alterations in expression of TGF-alpha mRNA differed from controls. Also, each individual tumor had a unique set of molecular alterations even when different tumors from the same animal were analyzed. These novel findings suggest that IGF-II, cyclin D1, c-myc and EGFR are important mediators of carcinogenesis in spontaneous mouse liver tumor formation. (C) 1997 Wiley-Liss, Inc. C1 CHEM IND INST TOXICOL,RES TRIANGLE PK,NC 27709. NIEHS,RES TRIANGLE PK,NC 27709. FU NIEHS NIH HHS [1 F32 ES05692-01A1] NR 38 TC 15 Z9 15 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD MAY PY 1997 VL 19 IS 1 BP 31 EP 38 DI 10.1002/(SICI)1098-2744(199705)19:1<31::AID-MC5>3.0.CO;2-Q PG 8 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA XC420 UT WOS:A1997XC42000005 PM 9180926 ER PT J AU Bocchinfuso, WP Korach, KS AF Bocchinfuso, WP Korach, KS TI Estrogen receptor residues required for stereospecific ligand recognition and activation SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID DIETHYLSTILBESTROL METABOLITES; BINDING DOMAIN; CRYSTAL-STRUCTURE; IN-VITRO; ANALOGS; ANTIESTROGENS; PROBES; SENSITIVITY; ANTAGONISTS; COMPLEXES AB The mouse estrogen receptor (mER) has been shown to exhibit stereospecific binding of certain stilbene estrogen agonists. The region of the mER involved in the stereochemical recognition of ligands was further defined using a stilbene isomer, Indenestrol B (IB). The IB compound has a chiral carbon bearing an ethyl substituent, and the wild type uterine mER has been shown to bind the enantiomers, IB-S and IB-R, with similar affinity. The wild type mER expressed in yeast exhibited a very minor preference for IB-S in transactivation (1.5-fold lower half-maximal dose than IB-R). The IB enantiomers could then be used to determine whether stereochemically distinct compounds with similar transcriptional activity utilize different amino acids in AF-2 for transactivation. Mutant mERs with glycine substitutions at Met521, His528, Met532, and Val537 were expressed in yeast and measured for IB-S- and IB-R-induced transactivation and ligand binding. The M532G mER showed a 124-fold and 50-fold reduction in transactivation induced by IB-S and IB-R, respectively, without a corresponding change in their ligand-binding affinities. Therefore, Met532 is required for transactivation induced by both IB enantiomers but does not discriminate based on stereospecificity. In contrast, the H528G mER displayed a gross change in stereospecific ligand recognition as illustrated by a 11O-fold reduction in transactivation by IB-S and only a 8.8-fold decrease in activity by IB-R. As a result, H528G mER displayed a switch in ligand preference such that IB-R was now 8-fold more active than IB-S in transactivation. Therefore, His528 appears largely involved in transactivation specifically induced by IB-S but has a minimal influence in IB-S ligand binding. The remaining mutant mERs displayed wild type ligand binding and transactivation properties for the IB enantiomers illustrating no stereospecific recognition. These results imply that individual IB enantiomers bind to the mER with similar affinity but utilize at least one different amino acid within the AF-2 domain for signal transduction. The binding of stereochemically distinct ligands may alter the tertiary structure of the mER and cause repositioning of the AF-2 region that mediates transcription of specific genes and/or affect the binding of receptor-associated proteins, such as coactivators, which could influence transcription. C1 NIEHS,RECEPTOR BIOL SECT,REPROD & DEV TOXICOL LAB,NIH,RES TRIANGLE PK,NC 27709. OI Korach, Kenneth/0000-0002-7765-418X NR 38 TC 14 Z9 14 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 MAY PY 1997 VL 11 IS 5 BP 587 EP 594 DI 10.1210/me.11.5.587 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WW609 UT WOS:A1997WW60900007 PM 9139802 ER PT J AU Wong, R Vasilyev, VV Ting, YT Kutler, DI Willingham, MC Weintraub, BD Cheng, SY AF Wong, R Vasilyev, VV Ting, YT Kutler, DI Willingham, MC Weintraub, BD Cheng, SY TI Transgenic mice bearing a human mutant thyroid hormone beta 1 receptor manifest thyroid function anomalies, weight reduction, and hyperactivity SO MOLECULAR MEDICINE LA English DT Article ID GENERALIZED RESISTANCE; LIGAND-BINDING; MOTOR-ACTIVITY; DISORDER; PROTEIN; ERBA; GENE; PERFORMANCE; EXPRESSION; KINDREDS AB Background: Resistance to thyroid hormone (RTH) is a syndrome characterized by refractoriness of the pituitary and/or peripheral tissues to the action of thyroid hormone. Mutations in the thyroid hormone receptor beta (TR beta) gene result in TR beta 1 mutants that mediate the clinical phenotype by interfering with transcription of thyroid hormone-regulated genes via a dominant negative effect. Ln this study, we developed transgenic mice harboring PV, a potent dominant negative human mutant TR beta 1 devoid of thyroid hormone binding and transcriptional activation, as an animal model to understand the molecular basis of this human disease. Materials and Methods: Standard molecular biology approaches were used to obtain a cDNA fragment containing mutant PV which was injected into the pronucleus of fertilized egg. Founders were identified by Southern analysis and the expression of PV in tissues was determined by RNA and immunohistochemistry. Thyroid function was determined by radioimmunoassays of the hormones and the behavior of mice was observed using standard methods. Results: The expression of mutant PV was directed by the beta-actin promoter. Mutant PV mRNA was detected in all tissues of transgenic mice, but the levels varied with tissues and with different lines of founders. Thyroid function tests in transgenic mice with high expression of mutant PV showed a significantly (similar to 1.5-fold) higher mean serum total of L-thyroxine levels (p < 0.01) than those of nontransgenic mice. Moreover, thyroid-stimulating hormone levels were not significantly different from those of nontransgenic mice. Zn addition, these mice displayed decreased weights and a behavioral phenotype characterized by hyperactivity. Conclusions: These mice have phenotypic features consistent with the commonly observed clinical features of RTH and could be used as a model system to better understand the action of mutant TR beta 1 in a physiological context, which could lead to better treatment for this disease. C1 NIDDKD,MOL & CELLULAR ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. NCI,MOL BIOL LAB,NIH,BETHESDA,MD 20892. MED UNIV S CAROLINA,DEPT PATHOL & LAB MED,CHARLESTON,SC 29425. NR 34 TC 32 Z9 33 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 1076-1551 J9 MOL MED JI Mol. Med. PD MAY PY 1997 VL 3 IS 5 BP 303 EP 314 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA XC147 UT WOS:A1997XC14700003 PM 9205946 ER PT J AU Husain, SR Gill, P Kreitman, RJ Pastan, I Puri, RK AF Husain, SR Gill, P Kreitman, RJ Pastan, I Puri, RK TI Interleukin-4 receptor expression on AIDS-associated Kaposi's sarcoma cells and their targeting by a chimeric protein comprised of circularly permuted interleukin-4 and Pseudomonas exotoxin SO MOLECULAR MEDICINE LA English DT Article ID CARCINOMA-CELLS; HIGH-AFFINITY; SIGNAL-TRANSDUCTION; IL-4 RECEPTORS; GAMMA-CHAIN; GROWTH; BINDING; IDENTIFICATION; PATHOGENESIS; MECHANISMS AB Background: AIDS-associated Kaposi's sarcoma (AIDS-KS) represents one of the most common malignancies associated with human immunodeficiency virus infection. To target effective therapeutic agents to AIDS-KS, we have identified a new target in the form of interleukin-4 receptors (IL-4R). Materials and Methods: The expression of IL-4R on AIDS-KS cells and their subunit structure was determined by radioligand receptor binding, cross-linking, and Northern and RT-PCR analyses. The in vitro effect of IL-4 and recombinant fusion protein made up of circularly permuted IL-4 and a mutated form of Pseudomonas exotoxin, IL-4(38-37)-PH38KDEL, was examined by clonogenic and protein synthesis inhibition assays. Results: Five AIDS-KS cell lines expressed high-affinity IL-4R with a K-d of 23.5-219 pM. IL-4 appeared to cross-link to one major protein corresponding to 140 kDa and a broad band corresponding to 60-70 kDa. Both cross-linked proteins were immunoprecipitated with an antibody to human IL-4R beta chain. AIDS-KS cells exhibited IL-4R beta-specific mRNA. IL-4 caused a modest inhibition (31-34%) of colony formation in two AIDS-KS cell lines tested. IL-4(38-37)-PE38KDEL was found to be highly effective in inhibiting the protein synthesis in all five AIDS-KS examined. The IC50 ranged from 32 to 1225 pM. The cytotoxic action of IL-4 toxin was blocked by an excess of IL-4, exhibiting the specificity of IL-4(38-37)-PE38KDEL. The cytotoxicity of IL-4 toxin observed by a donogenic assay corroborated well with the IC50 obtained by protein synthesis inhibition assay. Normal human endothelial cells expressed a negligible number of IL-4R (<50 sites/cell) and were less sensitive or not sensitive to IL-4(38-37)-PE38KDEL. Conclusion: The presence of a new plasma membrane protein in the form of IL-4R on AIDS-KS cells may be targeted by IL-4(38-37)-PE38KDEL for its potential implication in the treatment of AIDS-KS. C1 NIH,LAB MOL TUMOR BIOL,DIV CELLULAR & GENEN THERAPIES,CTR BIOL EVALUAT & RES,FOOD AND DRUG ADM,BETHESDA,MD 20892. UNIV SO CALIF,SCH MED,LOS ANGELES,CA. NCI,MOL BIOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 54 TC 37 Z9 39 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 1076-1551 J9 MOL MED JI Mol. Med. PD MAY PY 1997 VL 3 IS 5 BP 327 EP 338 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA XC147 UT WOS:A1997XC14700005 PM 9205948 ER PT J AU Chuaqui, RF Zhuang, ZP Merino, MJ AF Chuaqui, RF Zhuang, ZP Merino, MJ TI Molecular genetic events in the development and progression of ovarian cancer in humans SO MOLECULAR MEDICINE TODAY LA English DT Review ID STEROID-RECEPTORS; UNIFOCAL ORIGIN; BRCA1 GENE; LOW-GRADE; TUMORS; CARCINOMAS; CHROMOSOME-17; MUTATION; P53; HETEROZYGOSITY AB Ovarian tumor development is characterized by specific clinical and pathological features that provide an interesting model of carcinogenesis: first, the pre-invasive and even invasive lesions are difficult to detect; second, a group of cases with a known familial predilection constitute an important hereditary model of carcinogenesis; and third, the category of morphologically borderline ovarian tumors (tumors of low malignant potential) poses several unanswered questions such as: what histologic criteria should be used for their diagnosis; what is their natural history; and what is their molecular relationship to invasive tumors? Recently, molecular studies have contributed to a better understanding of the biology of these tumors, their behavior in vivo, and their response to therapy. This article summarizes the most recent molecular advances. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NR 49 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 1357-4310 J9 MOL MED TODAY JI Mol. Med. Today PD MAY PY 1997 VL 3 IS 5 BP 207 EP 213 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA WZ171 UT WOS:A1997WZ17100009 PM 9176883 ER PT J AU Tsuda, T Kusui, T Hou, W Benya, RV Akeson, MA Kroog, GS Battey, JF Jensen, RT AF Tsuda, T Kusui, T Hou, W Benya, RV Akeson, MA Kroog, GS Battey, JF Jensen, RT TI Effect of gastrin-releasing peptide receptor number on receptor affinity, coupling, degradation, and modulation SO MOLECULAR PHARMACOLOGY LA English DT Article ID HAMSTER OVARY CELLS; PROTEIN-KINASE-C; BOMBESIN-LIKE PEPTIDES; SWISS 3T3 CELLS; DOWN-REGULATION; BETA-2-ADRENERGIC RECEPTOR; TYROSINE PHOSPHORYLATION; CHRONIC DESENSITIZATION; EPITHELIAL-CELLS; ADENYLYL CYCLASE AB The relationship between receptor number and agonist-induced intracellular responses has been well studied in receptors coupled to adenylate cyclase; however, for receptors coupled to phospholipase C (PLC), very little is known about the effect of receptor number on receptor-mediated processes. To explore this issue, we investigated the effect of the number of receptors for gastrin-releasing peptide (GRP) on ligand affinity and on the ability to activate intracellular messengers [PLC, tyrosine phosphorylation of p125 focal adhesion kinase (p125(FAK))] and cause receptor modulation (internalization, desensitization, down-regulation) and ligand degradation. Three BALE 3T3 cell lines were made that stably expressed the gastrin-releasing peptide receptor (GRP-R) with receptor numbers varying by 280-fold (GRP-R-Low, GRP-R-Med, and GRP R-HI). Each cell line had the same affinity for agonist. The efficacy for bombesin to increase rt-l]inositol phosphates but not tyrosine phosphorylation of p125(FAK) correlated well with receptor number. In contrast, the EC50 value for [H-3]inositol phosphate generation for bombesin was the same in each cell line. Receptor number did not alter internalization. In the absence of protease inhibitors, there was an inverse correlation between receptor number and receptor down-regulation and desensitization. However, with protease inhibitors present, GRP-R-Med and GRP-R-Hi down-regulated significantly less than the GRP-R-Low. Similarly, GRP-R-Low desensitized significantly more than GRP-R-Med or GRP-R-Hi. GRP-R-HI caused significantly greater ligand degradation than GRP-R-Low, and protease inhibitors completely inhibited degradation by GRP-R-Low and inhibited degradation by 70% for GRP-R-Hi. In conclusion, we show that for the PLC-coupled GRP-R, receptor number had little or no effect on binding affinity, potency for activating PLC, tyrosine phosphorylation of p125(FAK). Or extent of receptor internalization. In contrast, receptor number had an effect on ligand degradation, down regulation, desensitization, and efficacy of PLC activation without altering the efficacy of tyrosine phosphorylation of p125(FAK) These results demonstrate that the effect of receptor number differs for the different functions mediated by the GRP receptor and differs from that reported for adenylate cyclase-coupled receptors such as receptors mediating the action of adrenergic agents, secretin, and opioids. C1 NIDDKD,DDB,NIH,BETHESDA,MD 20892. NIDCD,NIH,ROCKVILLE,MD 20850. NR 39 TC 29 Z9 29 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAY PY 1997 VL 51 IS 5 BP 721 EP 732 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WY280 UT WOS:A1997WY28000004 PM 9145910 ER PT J AU Higgins, JJ Pho, LT Ide, SE Nee, LE Polymeropoulos, MH AF Higgins, JJ Pho, LT Ide, SE Nee, LE Polymeropoulos, MH TI Evidence for a new spinocerebellar ataxia locus SO MOVEMENT DISORDERS LA English DT Article DE linkage analysis; dominantly inherited ataxia; spinocerebellar ataxia ID DOMINANT CEREBELLAR-ATAXIA; MACHADO-JOSEPH DISEASE; DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY; TRINUCLEOTIDE CAG REPEAT; CLINICAL-FEATURES; DREW FAMILY; GENE; MAPS; EXPANSION; EXISTENCE AB The autosomal dominant ataxias (ADA) are a diverse group of multisystem, neurodegenerative disorders characterized by mutations at several chromosomal loci (SCA types 1-5, SCA type 7, DRPLA). We excluded all the known SCA loci by mutational and linkage analyses in an American family of British origin with ADA and document that an additional ataxia locus must exist. The clinical characteristics and ethnic origin of our family are similiar to the British Drew family of Walworth with the SCA type 3 mutation and differ from other families without a known ataxia locus. individuals in our family and the Drew family initially show signs of ataxia but may develop variable degrees of sphthalmoplegia, Parkinsonian features and central demyelination. The phenotypic diversity in families without a known ataxia locus suggests that there may be several other undefined ataxia loci. C1 NIH,NATL CTR HUMAN DIS RES,LAB GENET DIS RES,GENE MAPPING UNIT,BETHESDA,MD 20892. RP Higgins, JJ (reprint author), NINCDS,MED NEUROL BRANCH,CLIN NEUROGENET UNIT,BLDG 10,ROOM 5N234,BETHESDA,MD 20892, USA. NR 24 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAY PY 1997 VL 12 IS 3 BP 412 EP 417 DI 10.1002/mds.870120322 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA WZ174 UT WOS:A1997WZ17400020 PM 9159738 ER PT J AU Wolffe, AP AF Wolffe, AP TI Transcriptional control - Sinful repression SO NATURE LA English DT Editorial Material RP Wolffe, AP (reprint author), NICHHD,MOL EMBRYOL LAB,NIH BLDG 18T,BETHESDA,MD 20892, USA. NR 17 TC 251 Z9 252 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 MAY 1 PY 1997 VL 387 IS 6628 BP 16 EP 17 DI 10.1038/387016a0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WW758 UT WOS:A1997WW75800020 PM 9139815 ER PT J AU Schmidt, L Duh, FM Chen, F Kishida, T Glenn, G Choyke, P Scherer, SW Zhuang, ZP Lubensky, I Dean, M Allikmets, R Chidambaram, A Bergerheim, UR Feltis, JT Casadevall, C Zamarron, A Bernues, M Richard, S Lips, CJM Walther, MM Tsui, LC Geil, L Orcutt, ML Stackhouse, T Lipan, J Slife, L Brauch, H Decker, J Niehans, G Hughson, MD Moch, H Storkel, S Lerman, MI Linehan, WM Zbar, B AF Schmidt, L Duh, FM Chen, F Kishida, T Glenn, G Choyke, P Scherer, SW Zhuang, ZP Lubensky, I Dean, M Allikmets, R Chidambaram, A Bergerheim, UR Feltis, JT Casadevall, C Zamarron, A Bernues, M Richard, S Lips, CJM Walther, MM Tsui, LC Geil, L Orcutt, ML Stackhouse, T Lipan, J Slife, L Brauch, H Decker, J Niehans, G Hughson, MD Moch, H Storkel, S Lerman, MI Linehan, WM Zbar, B TI Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas SO NATURE GENETICS LA English DT Article ID TUMOR-SUPPRESSOR GENE; MEDULLARY-THYROID CARCINOMA; RET PROTOONCOGENE; CELL CARCINOMA; C-MET; TRANSFORMING GENE; POINT MUTATION; GROWTH-FACTOR; SEQUENCE; RECEPTOR AB Hereditary papillary renal carcinoma (HPRC) is a recently recognized form of inherited kidney cancer characterized by a predisposition to develop multiple, bilateral papillary renal tumours(1-4). The pattern of inheritance of HPRC is consistent with autosomal dominant transmission with reduced penetrance. HPRC is histologically and genetically distinct from two other causes of inherited renal carcinoma, von Hippel-Lindau disease (VHL) and the chromosome translocation (3;8)(5-6). Malignant papillary renal carcinomas are characterized by trisomy of chromosomes 7, 16 and 17, and in men, by loss of the Y chromosome(7), Inherited and sporadic clear cell renal carcinomas are characterized by inactivation of both copies of the VHL gene by mutation, and/or by hypermethylation(8-11). We found that the HPRC gene was located at chromosome 7q31.1-34 in a 27-centimorgan (cM) interval between D7S496 and D7S1837. We identified missense mutations located in the tyrosine kinase domain of the MET gene in the germline of affected members of HPRC families and in a subset of sporadic Family: papillary renal carcinomas. Three mutations in the MET gene are located in codons that are homologous to those in c-kit and RET, proto-oncogenes that are targets of naturally-occurring mutations. The results suggest that missense mutations located in the MET proto-oncogene lead to constitutive activation of the MET protein and papillary renal carcinomas. C1 NCI,IMMUNOBIOL LAB,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NIH,GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892. NIH,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. HOSP SICK CHILDREN,DEPT GENET,TORONTO,ON M5G 1X8,CANADA. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NCI,LAB GEN DIVERS,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. KAROLINSKA HOSP,DEPT SURG,S-10401 STOCKHOLM,SWEDEN. CREDIT VALLEY HOSP,DEPT LAB MED,MISSISSAUGA,ON,CANADA. UNIV AUTONOMA BARCELONA,INST BIOL FONAMENTAL,E-08193 BARCELONA,SPAIN. HOSP COMARCAL SANTIAGO APOSTOL,BURGOS,SPAIN. HOP NECKER ENFANTS MALAD,LAB NEUROONCOL,PARIS,FRANCE. UNIV UTRECHT HOSP,UTRECHT,NETHERLANDS. NIH,SURG BRANCH,BETHESDA,MD 20892. UNIV HAMBURG,KRANKENHAUS EPPENDORF,D-2000 HAMBURG,GERMANY. UNIV MAINZ,DEPT HEMATOL & ONCOL,D-6500 MAINZ,GERMANY. INST PATHOL,WUPPERTAL,GERMANY. VET AFFAIRS,MINNEAPOLIS,MN 55362. VET AFFAIRS,NORTHPORT,NY 11768. UNIV BASEL,INST PATHOL,BASEL,SWITZERLAND. RP Schmidt, L (reprint author), SAIC FREDERICK,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD 21702, USA. RI Tsui, Lap-chee/A-1081-2010; Dean, Michael/G-8172-2012; Howe, Jennifer/I-9013-2012; Scherer, Stephen /B-3785-2013 OI Dean, Michael/0000-0003-2234-0631; Scherer, Stephen /0000-0002-8326-1999 NR 41 TC 863 Z9 876 U1 3 U2 33 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 1997 VL 16 IS 1 BP 68 EP 73 DI 10.1038/ng0597-68 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA WX024 UT WOS:A1997WX02400024 PM 9140397 ER PT J AU Chesebro, B AF Chesebro, B TI Human TSE disease - Viral or protein only? SO NATURE MEDICINE LA English DT Editorial Material ID CREUTZFELDT-JAKOB-DISEASE; MUTANT PRION PROTEIN; TRANSGENIC MICE; NEURODEGENERATION; MUTATION RP Chesebro, B (reprint author), NIAID,PERSISTENT VIRAL DIS LAB,ROCKY MT LABS,NIH,HAMILTON,MT 59840, USA. NR 16 TC 29 Z9 29 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 1997 VL 3 IS 5 BP 491 EP 492 DI 10.1038/nm0597-491 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA WX543 UT WOS:A1997WX54300020 PM 9142109 ER PT J AU Connors, M Kovacs, JA Krevat, S GeaBanacloche, JC Sneller, MC Flanigan, M Metcalf, JA Walker, RE Falloon, J Baseler, M Stevens, R Feuerstein, I Masur, H Lane, HC AF Connors, M Kovacs, JA Krevat, S GeaBanacloche, JC Sneller, MC Flanigan, M Metcalf, JA Walker, RE Falloon, J Baseler, M Stevens, R Feuerstein, I Masur, H Lane, HC TI HIV infection induces changes in CD4(+) T-cell phenotype and depletions within the CD4(+) T-cell repertoire that are not immediately restored by antiviral or immune-based therapies SO NATURE MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PERIPHERAL-BLOOD; MEMORY; LYMPHOCYTES; ANTIGEN; NAIVE; SUPERANTIGEN; REPLICATION; SEGMENTS; SUBSETS AB Changes in CD4(+) T-cell surface marker phenotype and antigen receptor (TCR) repertoire were examined during the course of HIV infection and following therapy. A preferential decline in naive CD4(+) T cells was noted as disease progressed. Following protease inhibitor therapy, naive CD4(+) T cells increased only if they were present before initiation of therapy. Disruptions of the CD4(+) TCR repertoire were most prevalent in patients with the lowest CD4(+) T-cell counts. Antiviral or IL-12 therapy-induced increases in CD4(+) T-cell counts led to only minor changes in previously disrupted repertoires. Thus, CD4(+) T-cell death mediated by HIV-1 infection may result in a preferential decline in the number of naive CD4(+) T cells and disruptions of the CD4(+) T-cell repertoire that are not immediately corrected by antiviral or immune-based therapies. C1 NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT CRIT CARE MED,BETHESDA,MD 20892. CLIN PUERTA DE HIERREO,SERV MED INTERNA 1,MADRID,SPAIN. NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP,FREDERICK,MD 21702. NR 40 TC 458 Z9 461 U1 0 U2 3 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 1997 VL 3 IS 5 BP 533 EP 540 DI 10.1038/nm0597-533 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA WX543 UT WOS:A1997WX54300033 PM 9142122 ER PT J AU Iafrati, MD Karas, RH Aronovitz, M Kim, S Sullivan, TR Lubahn, DB ODonnell, TF Korach, KS Mendelsohn, ME AF Iafrati, MD Karas, RH Aronovitz, M Kim, S Sullivan, TR Lubahn, DB ODonnell, TF Korach, KS Mendelsohn, ME TI Estrogen inhibits the vascular injury response in estrogen receptor alpha-deficient mice SO NATURE MEDICINE LA English DT Article ID SMOOTH-MUSCLE CELLS; ATHEROSCLEROTIC CORONARY-ARTERIES; NITRIC-OXIDE; MOUSE; EXPRESSION; ESTRADIOL; GENE; 17-BETA-ESTRADIOL; TRANSCRIPTION; ENDOTHELIUM AB The atheroprotective effects of estrogen in women are well recognized(1), but the underlying mechanisms responsible are not well understood. Blood vessel cells express the classic estrogen receptor, ER alpha (ref. 2-6), and are directly affected by estrogen, which inhibits the development of atherosclerotic and injury-induced vascular lesions(7,8). We have generated mice in which the ER alpha gene is disrupted(9) and have used a mouse model of carotid arterial injury to compare the effects of estrogen on wild-type and estrogen receptor-deficient mice. Increases in vascular medial area and smooth muscle cell proliferation were quantified following vascular injury in ovariectomized mice treated with vehicle or with physiologic levels of 17 beta-estradiol. Suprisingly, in both wild-type and estrogen receptor-deficient mice, 17 beta-estradiol markedly inhibited to the same degree all measures of vascular injury. These data demonstrate that estrogen inhibits vascular injury by a novel mechanism that is independent of the classic estrogen receptor, ER alpha. C1 TUFTS UNIV NEW ENGLAND MED CTR,MOL CARDIOL RES CTR,TUPPER RES INST,BOSTON,MA 02111. UNIV MISSOURI,DEPT BIOCHEM,COLUMBIA,MO 65201. UNIV MISSOURI,DEPT CHILD HLTH,COLUMBIA,MO 65201. NIEHS,REPROD & DEV TOXICOL LAB,NIH,RES TRIANGLE PK,NC 27709. OI Korach, Kenneth/0000-0002-7765-418X FU NHLBI NIH HHS [K08 HL 30386, R01 HL 56069] NR 44 TC 347 Z9 351 U1 0 U2 4 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 1997 VL 3 IS 5 BP 545 EP 548 DI 10.1038/nm0597-545 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA WX543 UT WOS:A1997WX54300035 PM 9142124 ER PT J AU Licinio, J Mantzoros, C Negrao, AB Cizza, G Wong, ML Bongiorno, PB Chrousos, GP Karp, B Allen, C Flier, JS Gold, PW AF Licinio, J Mantzoros, C Negrao, AB Cizza, G Wong, ML Bongiorno, PB Chrousos, GP Karp, B Allen, C Flier, JS Gold, PW TI Human leptin levels are pulsatile and inversely related to pituitary-adrenal function SO NATURE MEDICINE LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; HORMONE; VASOPRESSIN; RECEPTORS; RATS AB Leptin communicates nutritional status to regulatory centers in the brain(1,2). Because peripheral leptin influences the activity of the highly pulsatile adrenal and gonadal axes(3,4), we sought to determine whether leptin levels in the blood are pulsatile. We measured circulating leptin levels every 7 minutes for 24 hours, in six healthy men, and found that total circulating leptin levels exhibited a pattern indicative of pulsatile release, with 32.0 +/- 1.5 pulses every 24 hours and a pulse duration of 32.8 +/- 1.6 minutes. We also show an inverse relation between rapid fluctuations in plasma levels of leptin and those of adrenocorticotropic hormone (ACTH) and cortisol that could not be accounted for on the basis of glucocorticoid suppression of leptin. As leptin levels are pulsatile, we propose that a key function of the CNS is regulated by a peripheral pulsatile signal. In a separate pilot study we compared leptin pulsatility in 414 plasma samples collected every 7 minutes for 24 hours from one obese woman and one normal-weight woman. We found that high leptin levels in the obese subject were due solely to increased leptin pulse height; all concentration-independent pulsatility parameters were almost identical in the two women. Leptin pulsatility therefore can be preserved in the obese. C1 HARVARD UNIV,BETH ISRAEL DEACONESS MED CTR,SCH MED,DEPT MED,DIV ENDOCRINOL,BOSTON,MA 02215. NICHHD,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,BETHESDA,MD 20892. RP Licinio, J (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,NIH,BLDG 10,ROOM 2D46,10 CTR DR,BETHESDA,MD 20892, USA. RI Wong, Ma-Li/D-7903-2011; Negrao, Andre Brooking/C-9526-2014; Licinio, Julio/L-4244-2013 OI Negrao, Andre Brooking/0000-0002-8133-6723; Licinio, Julio/0000-0001-6905-5884 NR 29 TC 467 Z9 477 U1 0 U2 11 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 1997 VL 3 IS 5 BP 575 EP 579 DI 10.1038/nm0597-575 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA WX543 UT WOS:A1997WX54300042 PM 9142131 ER PT J AU Palm, GJ Zdanov, A Gaitanaris, GA Stauber, R Pavlakis, GN Wlodawer, A AF Palm, GJ Zdanov, A Gaitanaris, GA Stauber, R Pavlakis, GN Wlodawer, A TI The structural basis for spectral variations in green fluorescent protein SO NATURE STRUCTURAL BIOLOGY LA English DT Letter C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,HUMAN RETROVIRUS SECT,FREDERICK,MD 21702. RP Palm, GJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,PROT STRUCT SECT,MACROMOL STRUCT LAB,FREDERICK,MD 21702, USA. OI Stauber, Roland/0000-0002-1341-4523 NR 24 TC 198 Z9 202 U1 3 U2 17 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD MAY PY 1997 VL 4 IS 5 BP 361 EP 365 DI 10.1038/nsb0597-361 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA WX028 UT WOS:A1997WX02800010 PM 9145105 ER PT J AU Trus, BL Roden, RBS Greenstone, HL Vrhel, M Schiller, JT Booy, FP AF Trus, BL Roden, RBS Greenstone, HL Vrhel, M Schiller, JT Booy, FP TI Novel structural features of bovine papillomavirus capsid revealed by a three-dimensional reconstruction to 9 angstrom resolution SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID VIRUS-LIKE PARTICLES; CRYOELECTRON MICROSCOPY; 3-DIMENSIONAL STRUCTURE; ELECTRON-MICROGRAPHS; FUNCTIONAL IMPLICATIONS; SIMIAN VIRUS-40; TYPE-1 CAPSIDS; L1; PROTEINS; DNA AB The three-dimensional structure of bovine papillomavirus has been determined to 9 Angstrom resolution by reconstruction of high resolution, low dose cryo-electron micrographs of quench-frozen virions. Although hexavalent and pentavalent capsomeres form star-shaped pentamers of the major capsid protein L1, they have distinct high-resolution structures. Most prominently, a 25 Angstrom hole in the centre of hexavalent capsomeres is occluded in the pentavalent capsomeres. This raises the possibility that the 1.2 minor capsid protein is located in the centre of the pentavalent capsomeres. Intercapsomere connections similar to 10 Angstrom in diameter were clearly resolved. These link adjacent capsomeres and are reminiscent of the helical connections that stabilize polyomavirus. C1 NCI, CELLULAR ONCOL LAB, NIH, BETHESDA, MD 20892 USA. NIAMSD, STRUCT BIOL LAB, NIH, BETHESDA, MD 20892 USA. NIH, BIOMED ENGN & INSTRUMENTAT PROGRAM, NATL CTR RES RESOURCES, BETHESDA, MD 20892 USA. RP Trus, BL (reprint author), NCI, COMPUTAT BIOSCI & ENGN LAB, DIV COMP RES & TECHNOL, NIH, BETHESDA, MD 20892 USA. NR 56 TC 135 Z9 138 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD MAY PY 1997 VL 4 IS 5 BP 413 EP 420 DI 10.1038/nsb0597-413 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA WX028 UT WOS:A1997WX02800018 PM 9145113 ER PT J AU Hampel, H Teipel, SJ Kotter, HU Horwitz, B Pfluger, T Mager, T Moller, HJ MullerSpahn, F AF Hampel, H Teipel, SJ Kotter, HU Horwitz, B Pfluger, T Mager, T Moller, HJ MullerSpahn, F TI Structural magnetic resonance imaging in diagnosis and research of Alzheimer's disease SO NERVENARZT LA German DT Review DE magnetic resonance imaging; dementia; Alzheimer's disease; MR-volumetry; signal hyperintensity ID WHITE-MATTER LESIONS; MR SIGNAL ABNORMALITIES; INTERUNCAL DISTANCE; HIPPOCAMPAL-FORMATION; TEMPORAL-LOBE; NEUROFIBRILLARY TANGLES; PATHOLOGIC CORRELATION; CEREBRAL STRUCTURE; VASCULAR DEMENTIA; NORMAL VOLUNTEERS AB One of the most widely used neuroimaging procedures in Psychiatry and Neurology is magnetic resonance imaging (MRI). MRI has gained the position of a standard investigation in the differential diagnosis of dementia syndromes. In the clinical diagnosis of Alzheimer's disease (AD) MRI helps to improve the diagnostical accuracy. Recently new MRI-based techniques for performing volumetric measurement of cortical and subcortical structures have been developed. First reports indicate that MRI-based volumetric measurements can be accurate in differentiating AD patients from cognitively normal elderly individuals. These new techniques may be useful adjunct in assessing the clinical diagnosis of AD. Results could also yield insight in the fundamental pathology of the degenerative disease. It is the objective of this chapter to summarize and comment on the significance of MRI in the diagnosis and research of AD. Future directions are outlined, including the use of microscopic MRI,the differentiation of white matter signal hyperintensities and the combined evaluation of stuctural MRI and functional imaging techniques. C1 UNIV MUNICH,INST RADIOL DIAGNOST,D-80336 MUNICH,GERMANY. UNIV BASEL,PSYCHIAT KLIN & POLIKLIN,CH-4003 BASEL,SWITZERLAND. NIA,NEUROSCI LAB,NIH,BETHESDA,MD 20892. RP Hampel, H (reprint author), UNIV MUNICH,PSYCHIAT KLIN,FORSCH STN D2,GEDACHTNISAMBULANZ,PSYCHIAT KLIN & POLIKLIN,D-80336 MUNICH,GERMANY. NR 108 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0028-2804 J9 NERVENARZT JI Nervenarzt PD MAY PY 1997 VL 68 IS 5 BP 365 EP 378 DI 10.1007/s001150050138 PG 24 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA XD647 UT WOS:A1997XD64700001 PM 9280846 ER PT J AU Shimada, A Mukhin, A Ingram, DK London, ED AF Shimada, A Mukhin, A Ingram, DK London, ED TI N-methyl-D-aspartate receptor binding in brains of rats at different ages SO NEUROBIOLOGY OF AGING LA English DT Article DE NMDA receptor; dizocilpine; CGP 39653; aging brain; rat; binding assay; memory ID LONG-TERM POTENTIATION; H-3 CGP-39653 BINDING; ALZHEIMERS-DISEASE; ANTICONVULSANT MK-801; NMDA RECEPTOR; REGIONAL DISTRIBUTION; MK-801 BINDING; HUMAN HIPPOCAMPUS; TCP BINDING; FISCHER-344 RAT AB Potential age differences in N-methyl-D-aspartate (NMDA) receptor binding were evaluated in rat brain using [H-3]dizocilpine and [H-3]D,L-(E)-2-amino-4-propyl-5-phosphono-3-pentanoic acid (CGP 39653) as the radioligands. Neither [H-3]dizocilpine nor [H-3]CGP 39653 binding in hippocampus revealed any age difference (7 vs. 23-25 months) in B-max or K-d. High-affinity [H-3]dizocilpine binding showed a developmental increase (8 vs. 2 months) in hippocampus but not in frontal cortex. No senescence-related change (25 vs. 8 months) was observed in either region. The lack of senescence-related differences in these biochemical markers does not preclude the possibility of functional changes in the NMDA receptor with aging. Published by Elsevier Science Inc. C1 NIA,GERONTOL RES CTR,MOL PHYSIOL & GENET SECT,NIH,BALTIMORE,MD 21224. NIDA,BRAIN IMAGING SECT,INTRAMURAL RES PROGRAM,NIH,BALTIMORE,MD 21224. NR 55 TC 20 Z9 20 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAY-JUN PY 1997 VL 18 IS 3 BP 329 EP 333 DI 10.1016/S0197-4580(97)80315-6 PG 5 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA XQ587 UT WOS:A1997XQ58700010 PM 9263199 ER PT J AU Liao, DP Cooper, L Cai, JW Toole, J Bryan, N Burke, G Shahar, E Nieto, J Mosley, T Heiss, G AF Liao, DP Cooper, L Cai, JW Toole, J Bryan, N Burke, G Shahar, E Nieto, J Mosley, T Heiss, G TI The prevalence and severity of white matter lesions, their relationship with age, ethnicity, gender, and cardiovascular disease risk factors: The ARIC study SO NEUROEPIDEMIOLOGY LA English DT Article DE white matter lesions; age; ethnicity; gender; cardiovascular disease risk factors; cerebral MRI ID PERIVENTRICULAR LESIONS; ABNORMALITIES; ROTTERDAM; ADULTS; HEALTH; BRAIN; MRI AB White matter lesions (WMLs) detected by cerebral magnetic resonance imaging (MRI) are putatively a consequence of cerebral hypoperfusion or ischemia. We investigated the prevalence, severity and correlates of WMLs in a population-based sample of 1,920 African-American and European-American men and women aged 55-72 years, during the second follow-up examination of the Atherosclerosis Risk in Communities Study. The spin density images from 1.5-tesla MRI scans were used to define WMLs using a 0-9 scale with 0 for normal and 9 for most severe WMLs. Age was positively associated with the prevalence (percent) and severity of WMLs. African-Americans had a lower overall prevalence of WMLs, but a higher prevalence of relatively more severe WMLs, than European-Americans. After adjusting for age, sex, and ethnicity, WMLs were significantly associated with smoking, lower education, hypertension, systolic blood pressure, and pulse pressure, and weakly associated with diastolic blood pressure. The associations of smoking, alcohol intake, systolic and diastolic blood pressure, pulse, pressure, and hypertension were stronger in African-Americans than in European-Americans (p < 0.15 for interactions by ethnicity). This population-based MRI study documents significant relationships between several cardiovascular disease risk factors and WMLs. The findings suggest that such factors play a role in the pathogenesis of WMLs, as elements linked to hypoperfusion and/or fluid accumulation, which presumably lead to WMLs. African-Americans exhibited both a higher proportion of normal white matter and a higher proportion of relatively more severe WMLs than European-Americans. C1 UNIV N CAROLINA,DEPT BIOSTAT,CHAPEL HILL,NC 27514. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT NEUROL,WINSTON SALEM,NC 27103. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. JOHNS HOPKINS UNIV,SCH MED,DEPT RADIOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21205. UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,MINNEAPOLIS,MN 55455. UNIV MISSISSIPPI,MED CTR,DEPT MED,JACKSON,MS 39216. RP Liao, DP (reprint author), UNIV N CAROLINA,SCH PUBL HLTH,DEPT EPIDEMIOL,137 E FRANKLIN ST,NATIONS BANK PLAZA,SUITE 306,CHAPEL HILL,NC 27514, USA. FU NHLBI NIH HHS [N01-HC-55018, N01-HC-55019, N01-HC-55021] NR 19 TC 274 Z9 283 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PD MAY-JUN PY 1997 VL 16 IS 3 BP 149 EP 162 PG 14 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA WY128 UT WOS:A1997WY12800006 PM 9159770 ER PT J AU Clauw, DJ Chrousos, GP AF Clauw, DJ Chrousos, GP TI Chronic pain and fatigue syndromes: Overlapping clinical and neuroendocrine features and potential pathogenic mechanisms SO NEUROIMMUNOMODULATION LA English DT Review DE fibromyalgia; chronic fatigue syndrome; pain; fatigue ID IRRITABLE-BOWEL-SYNDROME; CORTICOTROPIN-RELEASING-FACTOR; FIBROMYALGIA FIBROSITIS SYNDROME; POSTTRAUMATIC-STRESS-DISORDER; AUTONOMIC NERVOUS-SYSTEM; PITUITARY-ADRENAL AXIS; MAGNETIC-RESONANCE SPECTROSCOPY; COGNITIVE-BEHAVIORAL TREATMENT; CHILD SEXUAL ABUSE; SUBSTANCE-P AB Patients with unexplained chronic pain and/or fatigue have been described for centuries in the medical literature, although the terms used to describe these; symptom complexes have changed frequently. The currently preferred terms for these syndromes are fibromyalgia and chronic fatigue syndrome, names which describe the prominent clinical features of the illness without any attempt to identify the cause. This review delineates the definitions of these syndromes, and the overlapping clinical features. A hypothesis is presented to demonstrate how genetic and environmental factors may interact to cause the development of these syndromes, which we postulate are caused by central nervous system dysfunction. Various components of the central nervous system appear to be involved, including the hypothalamic pituitary axes, pain-processing pathways, and autonomic nervous system. These central nervous system changes lead to corresponding changes in immune function, which we postulate are epiphenomena rather than the cause of the illnesses. C1 Georgetown Univ, Med Ctr, Dept Med, Div Rheumatol Allergy & Immunol, Washington, DC 20007 USA. NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. RP Clauw, DJ (reprint author), Georgetown Univ, Med Ctr, Dept Med, Div Rheumatol Allergy & Immunol, 3800 Reservoir Rd NW, Washington, DC 20007 USA. FU NIDDK NIH HHS [R01 DK-49515] NR 192 TC 269 Z9 273 U1 2 U2 16 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PD MAY-JUN PY 1997 VL 4 IS 3 BP 134 EP 153 PG 20 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA YV032 UT WOS:000071782800004 PM 9500148 ER PT J AU Rapoport, JL InoffGermain, G AF Rapoport, JL InoffGermain, G TI Medical and surgical treatment of obsessive-compulsive disorder SO NEUROLOGIC CLINICS LA English DT Article ID NEUROSURGICAL TREATMENT; DOUBLE-BLIND; ADJUVANT BUSPIRONE; TOURETTES-SYNDROME; TREATED PATIENTS; FOLLOW-UP; CLOMIPRAMINE; TICS; FLUOXETINE; OXYTOCIN AB Current treatment outcomes for obsessive-compulsive disorder patients are far better than in past decades, but variability in treatment response remains. Most obsessive-compulsive disorder patients, but not all, respond to antidepressant agents with prominent serotonin uptake blocking properties. Because clomipramine's usefulness is limited by side effects which often accompany its use, a considerable degree of attention has shifted to selective serotonin reuptake inhibitors. A number of studies have also provided evidence for the effectiveness of medication other than those mainly involving serotonergic function, either as augmenting agents or for comorbid disorders. Neurosurgery may be useful for highly selected subjects. RP Rapoport, JL (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,10 CTR DR,MSC 1600,BETHESDA,MD 20892, USA. NR 41 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0733-8619 J9 NEUROL CLIN JI Neurol. Clin. PD MAY PY 1997 VL 15 IS 2 BP 421 EP & DI 10.1016/S0733-8619(05)70323-6 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WX694 UT WOS:A1997WX69400016 PM 9115472 ER PT J AU Wichman, A Sandler, AL AF Wichman, A Sandler, AL TI Research involving critically ill subjects in emergency circumstances: New regulations, new challenges SO NEUROLOGY LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the American-Academy-of-Neurology CY APR-MAY -, 1995 CL SEATTLE, WA SP Amer Acad Neurol ID INFORMED CONSENT RP Wichman, A (reprint author), NIH,OFF HUMAN SUBJECTS RES,BLDG 10,RM 1C-116,BETHESDA,MD 20892, USA. NR 11 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 1997 VL 48 IS 5 BP 1151 EP 1155 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA WZ778 UT WOS:A1997WZ77800001 PM 9153435 ER PT J AU Nelson, KA Park, KM Robinovitz, E Tsigos, C Max, MB AF Nelson, KA Park, KM Robinovitz, E Tsigos, C Max, MB TI High-dose oral dextromethorphan versus placebo in painful diabetic neuropathy and postherpetic neuralgia SO NEUROLOGY LA English DT Article ID RECEPTOR ANTAGONIST KETAMINE; NMDA ANTAGONIST; DOUBLE-BLIND; INTRAVENOUS LIDOCAINE; RELIEVES; AMITRIPTYLINE; RAT; DESIPRAMINE; MORPHINE; TRIAL AB N-methyl-D-aspartate (NMDA) receptor antagonists relieve neuropathic pain in animal models, but side effects of dissociative anesthetic channel blockers, such as ketamine, have discouraged clinical application. Based on the hypothesis that low-affinity NMDA channel blockers might have a better therapeutic ratio, we carried out two randomized, double-blind, crossover trials comparing six weeks of oral dextromethorphan to placebo in two groups, made up of 14 patients with painful distal symmetrical diabetic neuropathy and 18 with postherpetic neuralgia. Thirteen patients with each diagnosis completed the comparison. Dosage was titrated in each patient to the highest level reached without disrupting normal activities; mean doses were 381 mg/day in diabetics and 439 mg/day in postherpetic neuralgia patients. In diabetic neuropathy, dextromethorphan decreased pain by a mean of 24% (95% CI: 6% to 42%, p = 0.01), relative to placebo. In postherpetic neuralgia, dextromethorphan did not reduce pain (95% CI: 10% decrease in pain to 14% increase in pain, p = 0.72). Five of 31 patients who took dextromethorphan dropped out due to sedation or ataxia during dose escalation, but the remaining patients all reached a reasonably well-tolerated maintenance dose. We conclude that dextromethorphan or other low-affinity NMDA channel blockers may have promise in the treatment of painful diabetic neuropathy. C1 NIDR, PAIN & NEUROSENSORY MECHANISMS BRANCH, NIH, BETHESDA, MD 20892 USA. NICHHD, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD USA. NIH, DEPT NURSING, CTR CLIN, BETHESDA, MD 20892 USA. NR 49 TC 235 Z9 245 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 1997 VL 48 IS 5 BP 1212 EP 1218 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA WZ778 UT WOS:A1997WZ77800011 PM 9153445 ER PT J AU Chen, R Classen, J Gerloff, C Celnik, P Wassermann, EM Hallett, M Cohen, LG AF Chen, R Classen, J Gerloff, C Celnik, P Wassermann, EM Hallett, M Cohen, LG TI Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation SO NEUROLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Neurological-Association CY OCT 13-16, 1996 CL MIAMI, FL SP Amer Neurol Assoc ID LONG-TERM DEPRESSION; SYNAPTIC PLASTICITY; AREA CA1; HIPPOCAMPUS; MECHANISMS; RESPONSES; LTP AB We studied the effects of low-frequency transcranial magnetic stimulation (TMS) on motor cortex excitability in humans. TMS at 0.1 Hz for 1 hour did not change cortical excitability. Stimulation at 0.9 Hz for 15 minutes (810 pulses), similar to the parameters used to induce long-term depression (LTD) in cortical slice preparations and in vivo animal studies, led to a mean decrease in motor evoked potential (MEP) amplitude of 19.5%. The decrease in cortical excitability lasted for at least 15 minutes after the end of the 0.9 Hz stimulation. The mechanism underlying this decrease in excitability may be similar to LTD. TMS-induced reduction of cortical excitability has potential clinical applications in diseases such as epilepsy and myoclonus. Spread of excitation, which may be a warning sign for seizures, occurred in one subject and was not accompanied by increased MEP amplitude, suggesting that spread of excitation and amplitude changes are different phenomena and also indicating the need for adequate monitoring even with stimulations at low frequencies. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,HUMAN CORT PHYSIOL UNIT,BETHESDA,MD 20892. RI Chen, Robert/B-3899-2009 OI Chen, Robert/0000-0002-8371-8629 NR 25 TC 1170 Z9 1212 U1 6 U2 47 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 1997 VL 48 IS 5 BP 1398 EP 1403 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA WZ778 UT WOS:A1997WZ77800046 PM 9153480 ER PT J AU Calabresi, PA Stone, LA Bash, CN Frank, JA McFarland, HF AF Calabresi, PA Stone, LA Bash, CN Frank, JA McFarland, HF TI Interferon beta results in immediate reduction of contrast-enhanced MRI lesions in multiple sclerosis patients followed by weekly MRI SO NEUROLOGY LA English DT Article ID EDSS AB Interferon beta-1a and -1b reduce the frequency and severity of clinical exacerbations, and reduce both T-2-weighted and contrast-enhanced MRI activity in patients with multiple sclerosis (MS). Several recent reports suggest that at the initiation of treatment there may be transient worsening of symptoms associated with the induction of interferon gamma-secreting cells. We studied eight MS patients with weekly brain MRI's after starting interferon beta treatment, and found immediate reduction in the number of contrast-enhancing lesions. Several patients did experience recurrence of previous symptoms without concomitant opening of the blood brain barrier on contrast-enhanced MRI. These data suggest that the symptoms described after the initiation of interferon beta are not associated with new disease activity, but rather may be related to preexisting lesions. This has implications for both understanding the immunopathogenesis of the disease and for its treatment. C1 NIH,LAB DIAGNOST RADIOL RES,OFF DIRECTOR,BETHESDA,MD 20892. MAYO CLIN SCOTTSDALE,DEPT NEUROL,SCOTTSDALE,AZ. RP Calabresi, PA (reprint author), NINCDS,NEUROIMMUNOL BRANCH,NIH,ROOM 5B-16,10 CTR DR,MSC-1400,BETHESDA,MD 20892, USA. NR 10 TC 66 Z9 67 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 1997 VL 48 IS 5 BP 1446 EP 1448 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA WZ778 UT WOS:A1997WZ77800055 PM 9153489 ER PT J AU Baloh, RH Tansey, MG Golden, JP Creedon, DJ Heuckeroth, RO Keck, CL Zimonjic, DB Popescu, NC Johnson, EM Milbrandt, J AF Baloh, RH Tansey, MG Golden, JP Creedon, DJ Heuckeroth, RO Keck, CL Zimonjic, DB Popescu, NC Johnson, EM Milbrandt, J TI TrnR2, a novel receptor that mediates neurturin and GDNF signaling through Ret SO NEURON LA English DT Article ID NERVE GROWTH-FACTOR; PROGRAMMED CELL-DEATH; NEUROTROPHIC FACTOR; IN-VIVO; SYMPATHETIC NEURONS; NONNEURONAL CELLS; GENE-EXPRESSION; SURVIVAL FACTOR; MOTOR-NEURONS; MESSENGER-RNA AB Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) comprise a family of TGF-P-related neurotrophic factors (TRNs), which have trophic influences on a variety of neuronal populations. A receptor complex comprised of TrnR1 (GDNFR alpha) and Ret was recently identified and found to be capable of mediating both GDNF and NTN signaling. We have identified a novel receptor based on homology to TrnR1, called TrnR2, that is 48% identical to TrnR1, and is located on the short arm of chromosome 8. TrnR2 is attached to the cell surface via a GPI-linkage, and can mediate both NTN and GDNF signaling through Ret in vitro. Fibroblasts expressing TrnR2 and Ret are similar to 30-fold more sensitive to NTN than to GDNF treatment, whereas those expressing TrnR1 and Ret respond equivalently to both factors, suggesting the TrnR2-Ret complex acts preferentially as a receptor for NTN. TrnR2 and Ret are expressed in neurons of the superior cervical and dorsal root ganglia, and in the adult brain. Comparative analysis of TrnR1, TrnR2, and Ret expression indicates that multiple receptor complexes, capable of mediating GDNF and NTN signaling, exist in vivo. C1 WASHINGTON UNIV,SCH MED,DEPT INTERNAL MED,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT NEUROL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT MOL BIOL & PHARMACOL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT PEDIAT,ST LOUIS,MO 63110. NCI,EXPT CARCINOGENESIS LAB,BETHESDA,MD 20892. RP Baloh, RH (reprint author), WASHINGTON UNIV,SCH MED,DEPT PATHOL,ST LOUIS,MO 63110, USA. OI Heuckeroth, Robert/0000-0002-3282-1765 FU NIA NIH HHS [R01 AG13729, R01 AG13730] NR 47 TC 276 Z9 285 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD MAY PY 1997 VL 18 IS 5 BP 793 EP 802 DI 10.1016/S0896-6273(00)80318-9 PG 10 WC Neurosciences SC Neurosciences & Neurology GA XB722 UT WOS:A1997XB72200012 PM 9182803 ER PT J AU Su, TP Schmidt, PJ Danaceau, MA Tobin, MB Rosenstein, DL Murphy, DL Rubinow, DR AF Su, TP Schmidt, PJ Danaceau, MA Tobin, MB Rosenstein, DL Murphy, DL Rubinow, DR TI Fluoxetine in the treatment of premenstrual dysphoria SO NEUROPSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 19-23, 1993 CL SAN FRANCISCO, CA SP Soc Biol Psychiat DE fluoxetine; serotonin; premenstrual dysphoric disorder (PMDD); m-chlorophenylpiperazine (m-CPP); follicular phase; luteal phase ID OBSESSIVE-COMPULSIVE DISORDER; PLACEBO-CONTROLLED TRIAL; INDUCED SEXUAL DYSFUNCTION; MAJOR DEPRESSIVE DISORDER; DOUBLE-BLIND; SSRI ANTIDEPRESSANTS; DOSE FLUOXETINE; CLOMIPRAMINE; MOOD; ALPRAZOLAM AB We performed a double-blind, placebo-controlled, crossover trial of fluoxetine in 17 women with prospectively confirmed PMS who also met criteria for premenstrual dysphoric disorder (PMDD). A subset of 10 women with PMDD and an additional 10 controls participated in a single-dose m-chlorophenylpiperazine (m-CPP) challenge during the follicular and luteal phases of the menstrual cycle. We evaluated the ability of the acute behavioral response to luteal phase m-CPP administration to predict therapeutic response to fluoxetine. Compared with baseline, fluoxetine, but not placebo, treatment significantly improved both emotional and physical symptoms. We identified 11 (65%) fluoxetine responders who no longer met diagnostic criteria for PMDD during fluoxetine but remained symptomatic during placebo treatment. In addition, acute symptomatic improvement also occurred following m-CPP administration in 7 of 10 women with PMDD. The small number of m-CPP nonresponders did not respond to fluoxetine either. Our findings confirm that fluoxetine is an effective treatment of PMDD. (C) Published 1997 by Elsevier Science Inc. RP Su, TP (reprint author), NIMH,BLDG 10,ROOM 3N238,10 CTR DR,MSC 1276,BETHESDA,MD 20892, USA. NR 49 TC 70 Z9 71 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 1997 VL 16 IS 5 BP 346 EP 356 DI 10.1016/S0893-133X(96)00245-X PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA WT843 UT WOS:A1997WT84300005 PM 9109106 ER PT J AU Quarles, RH AF Quarles, RH TI The spectrum and pathogenesis of antibody-mediated neuropathies SO NEUROSCIENTIST LA English DT Article DE antibody; ganglioside; myelin-associated glycoprotein; neuropathy; sulfoglucuronyl paragloboside ID MYELIN-ASSOCIATED GLYCOPROTEIN; GUILLAIN-BARRE-SYNDROME; MOTOR-NEURON DISEASE; ANTI-GM1 ANTIBODIES; PERIPHERAL-NERVE; MONOCLONAL IGM; SPINAL-CORD; IMMUNOGLOBULIN-M; GM1 GANGLIOSIDE; NORTHERN CHINA AB Antibodies reacting with carbohydrate epitopes on neural glycoconjugates are present in several forms of neuropathy. These include monoclonal antibodies to the myelin-associated glycoprotein (MAG) and to gangliosides in patients with neuropathy in association with IgM gammopathy, as well as polyclonal antibodies to gangliosides in inflammatory polyneuropathies, such as Guillain-Barre syndrome and multifocal motor neuropathy. There are several correlations between antibody specificity and clinical symptoms, including anti-MAG antibodies with demyelinating sensory or sensorimotor neuropathy, anti-GM1 ganglioside antibodies with motor nerve disorders, anti-GQ1b ganglioside antibodies with Miller-Fisher syndrome, and antibodies to gangliosides containing disialosyl moieties with sensory ataxic neuropathy, This review will emphasize recent developments concerning the origins of the anti-glycoconjugate antibodies in patients, pathogenic mechanisms by which the antibodies may cause the neuropathies, and the implications of these findings for therapy. C1 NINCDS, MOL & CELLULAR BIOL LAB, NIH, BETHESDA, MD 20892 USA. NR 58 TC 5 Z9 5 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 EI 1089-4098 J9 NEUROSCIENTIST JI Neuroscientist PD MAY PY 1997 VL 3 IS 3 BP 195 EP 204 DI 10.1177/107385849700300313 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA XC961 UT WOS:A1997XC96100013 ER PT J AU Dence, CS John, CS Bowen, WD Welch, MJ AF Dence, CS John, CS Bowen, WD Welch, MJ TI Synthesis and evaluation of [F-18] labeled benzamides: High affinity sigma receptor ligands for PET imaging SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE fluorine-18; positron emission tomography; benzamides; sigma receptors ID MALIGNANT-MELANOMA; AUTORADIOGRAPHIC LOCALIZATION; ANTIPSYCHOTIC-DRUGS; BINDING-SITES; GUINEA-PIG; BRAIN; TUMORS; CELLS AB We have synthesized and characterized four new fluorinated halobenzamides as sigma receptor ligands for use with positron emission tomography (PET). All the compounds were found to have high sigma-1 affinities (K-i = 0.38-0.98 nM), and the 4-fluoro substituted benzamides were found to he more potent sigma-2 ligands (K-i = 3.77-4.02 nM) than their corresponding 2-fluoro analogs (K-i = 20.3-22.8 nM). The [F-18] radiochemical syntheses of two of the analogs gave overall yields between 3-10% (EOS), radiochemical purities >99%, and specific activities between 800-1200 Ci/mmol (29.6-44.4 TBq/mmol). Rat biodistribution and blocking experiments were performed with 2-[F-18]( N-fluorobenzylpiperidin-4yl)-4-iodobenzamide, the analog with the best K-i value for sigma-1 sites (0.38 nM). Results of these experiments demonstrate specific uptake of the compound in tissues believed to contain sigma receptors, such as lungs, kidneys, heart, brain, and spleen and indicate its potential as a candidate for use in PET imaging of tissues containing these receptors. (C) 1997 Elsevier Science Inc. C1 WASHINGTON UNIV,SCH MED,MALLINCKRODT INST RADIOL,ST LOUIS,MO 63110. GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20037. NIDDKD,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [CA58496]; NHLBI NIH HHS [P01HL13851] NR 34 TC 38 Z9 42 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0883-2897 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD MAY PY 1997 VL 24 IS 4 BP 333 EP 340 DI 10.1016/S0969-8051(97)00001-2 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA XG563 UT WOS:A1997XG56300008 PM 9257332 ER PT J AU Neuwald, AF Liu, JS Lipman, DJ Lawrence, CE AF Neuwald, AF Liu, JS Lipman, DJ Lawrence, CE TI Extracting protein alignment models from the sequence database SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DEHYDROGENASE MULTIENZYME COMPLEX; BUD-SITE SELECTION; YEAST PYRUVATE-CARBOXYLASE; GRAM-NEGATIVE BACTERIA; HIDDEN MARKOV-MODELS; AMINO-ACID-SEQUENCES; SACCHAROMYCES-CEREVISIAE; LIPOYL DOMAIN; 3-DIMENSIONAL STRUCTURE; PROFILE ANALYSIS AB Biologists often gain structural and functional insights into a protein sequence by constructing a multiple alignment model of the family. Here a program called PROBE fully automates this process of model construction starting from a single sequence. Central to this program is a powerful new method to locate and align only those, often subtly, conserved patterns essential to the family as a whole. When applied to randomly chosen proteins, PROBE found on average about four times as many relationships as a pairwise search and yielded many new discoveries, These include: an obscure subfamily of globins in the roundworm Caenorhabditis elegans; two new superfamilies of metallohydrolases; a lipoyl/biotin swinging arm domain in bacterial membrane fusion proteins; and a DH domain in the yeast Bud3 and Fus2 proteins. By identifying distant relationships and merging families into superfamilies in this way, this analysis further confirms the notion that proteins evolved from relatively few ancient sequences, Moreover, this method automatically generates models of these ancient conserved regions for rapid and sensitive screening of sequences. C1 STANFORD UNIV,DEPT STAT,STANFORD,CA 94305. NEW YORK STATE DEPT HLTH,WADSWORTH CTR LABS & RES,BIOMETR LAB,ALBANY,NY 12201. RP Neuwald, AF (reprint author), NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BLDG 10,BETHESDA,MD 20892, USA. FU NHGRI NIH HHS [1RO1-HG0125701] NR 90 TC 186 Z9 189 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY 1 PY 1997 VL 25 IS 9 BP 1665 EP 1677 DI 10.1093/nar/25.9.1665 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WX781 UT WOS:A1997WX78100001 PM 9108146 ER PT J AU Sander, M AF Sander, M TI In situ activity gel for DNA repair 3'-phosphodiesterase SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ESCHERICHIA-COLI; EXONUCLEASE-III; ENDONUCLEASE-IV; DAMAGE; ENZYME; BLEOMYCIN; CELLS AB An enzyme that plays an important role in the repair of oxidative DNA damage is the 3'-phosphodiesterase. This activity, which repairs damaged DNA 3'-termini, can be detected using several available biochemical assays, We present a method to detect 3'-phosphodiesterase activity of renatured proteins immobilized in polyacrylamide gels, The model substrate, labeled with [alpha-P-32]dCTP, contains 3'-phosphoglycolate termini produced by bleomycin-catalyzed cleavage of the self-complementary alternating copolymer poly(dGdC). The DNA substrate is incorporated into the gel matrix during standard SDS-PAGE, Active 3'-phosphodiesterase enzymes are detected visibly by the loss of radioactivity at a position corresponding to the mobility of the enzyme during SDS-PAGE. Using this procedure, two Escherichia coli 3'-phosphodiesterases, exonuclease III and endonuclease IV, are readily detected in crude cell extracts or as homogeneous purified proteins, Extracts of mutant cells lack activity at the positions of exonuclease III and endonuclease IV but retain activity in the position of a much larger protein (M-r approximate to 100 kDa). The identification of this novel 100 kDa E. coli 3'-phosphodiesterase demonstrates the potential value of the activity gel method described here. RP Sander, M (reprint author), NIEHS,MOL GENET LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 14 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY 1 PY 1997 VL 25 IS 9 BP 1868 EP 1869 DI 10.1093/nar/25.9.1868 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WX781 UT WOS:A1997WX78100031 PM 9108175 ER PT J AU Kim, TJ Anasti, JN Flack, MR Kimzey, LM Defensor, RA Nelson, LM AF Kim, TJ Anasti, JN Flack, MR Kimzey, LM Defensor, RA Nelson, LM TI Routine endocrine screening for patients with karyotypically normal spontaneous premature ovarian failure SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID AUTOIMMUNE-DISEASE AB Objective: To evaluate the usefulness of routine screening for other associated autoimmune endocrine disorders in patients with karyotypically normal spontaneous premature ovarian failure. Methods: One hundred nineteen women with karyotypically normal spontaneous premature ovarian failure (FSH exceeding 40 mIU/mL) who desired fertility were evaluated at a tertiary care academic center by physical examination, measurement of serum free thyroxine and TSH, ACTH stimulation test, fasting serum glucose, 3-hour glucose tolerance test, measurement of serum electrolytes including total calcium, and measurement of serum vitamin B-12. Results: Twenty-two of 119 patients (18.5%) were known to have hypothyroidism and three were known to have Addison disease. Ten new cases of hypothyroidism and three new cases of diabetes mellitus were discovered. However, no new cases of adrenal insufficiency, hypoparathyroidism, or pernicious anemia were found. Conclusion: Screening for hypothyroidism and diabetes appears justified in those patients with karyotypically normal spontaneous premature ovarian failure who desire fertility. However, our findings suggest that in these patients, testing for other associated autoimmune endocrine disorders may be reserved for those with clinical indications. (C) 1997 by The American College of Obstetricians and Gynecologists. C1 NATL INST HLTH,CTR CLIN,DEPT NURSING,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,SECT WOMENS HLTH,BETHESDA,MD 20892. NR 13 TC 68 Z9 71 U1 0 U2 0 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 MAY PY 1997 VL 89 IS 5 BP 777 EP 779 DI 10.1016/S0029-7844(97)00077-X PN 1 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA WV953 UT WOS:A1997WV95300028 PM 9166320 ER PT J AU Bush, MR Walmer, DK Couchman, GM Haney, AF AF Bush, MR Walmer, DK Couchman, GM Haney, AF TI Evaluation of the postcoital test in cycles involving exogenous gonadotropins SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID INSEMINATION AB Objective: To evaluate the hypothesis that a postcoital test, optimally performed in the periovulatory period of cycles in which gonadotropin-induced superovulation was used, correlates with cycle fecundity. Methods: Of 1135 total consecutive cycles, 367 first cycles were analyzed from the reproductive endocrinology and infertility service of a university medical center. This referral population had a mean age of 34.6 years for the female partner, a nulliparity rate of 81%, and a mean length of infertility of 4.8 years. Postcoital tests were performed 36-40 hours after hCG administration in gonadotropin-stimulated cycles. Clinical pregnancy was defined as fetal cardiac activity as seen on transvaginal ultrasound examination. Results: Couples with no sperm observed per high-power field in the cervical mucus achieved a 16% fecundity rate (21 pregnancies in 129 cycles), one to ten sperm a 18% fecundity rate (28 pregnancies in 154 cycles), and more than ten sperm a 15% fecundity rate (13 pregnancies in 84 cycles). There was no significant difference between groups (n = 367, P = .85); the power to detect a statistically significant difference was .82. As validation of optimal cervical mucus, fecundity rates were compared with these postcoital test values across the entire range of peak periovulatory serum estrogen levels, and no correlation was seen (P = .61, .86, and .96 for estrogen levels of 201-500, 501-1500, and 1501-3433 pg/mL, respectively). Conclusion: With precise periovulatory timing and supraphysiologic estrogen levels optimizing qualitative cervical mucus characteristics in gonadotropin-induced cycles, the number of sperm observed per high-power field does not correlate with cycle fecundity. (C) 1997 by The American College of Obstetricians and Gynecologists. C1 NIEHS,REPROD & DEV TOXICOL LAB,NATL INST HLTH,RES TRIANGLE PK,NC 27709. RP Bush, MR (reprint author), DUKE UNIV,MED CTR,DEPT OBSTET & GYNECOL,DIV REPROD ENDOCRINOL & INFERTIL,BOX 3143,DURHAM,NC 27710, USA. NR 9 TC 2 Z9 2 U1 0 U2 0 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 MAY PY 1997 VL 89 IS 5 BP 780 EP 784 DI 10.1016/S0029-7844(97)00071-9 PN 1 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA WV953 UT WOS:A1997WV95300029 PM 9166321 ER PT J AU Harvat, BL Seth, P Jetten, AM AF Harvat, BL Seth, P Jetten, AM TI The role of p27(Kip1) in gamma interferon-mediated growth arrest of mammary epithelial cells and related defects in mammary carcinoma cells SO ONCOGENE LA English DT Article DE p27(Kip1); growth inhibition; mammary epithelial cells; cdk2; cyclin E; mammary carcinoma ID CYCLIN-DEPENDENT KINASES; RETINOBLASTOMA PROTEIN; CDK INHIBITORS; TGF-BETA; DNA-REPLICATION; BREAST-CANCER; TRANSFORMING GROWTH-FACTOR-BETA-1; POTENTIAL MEDIATOR; GENE-EXPRESSION; MAMMALIAN-CELLS AB Interferon gamma (IFN gamma) induces growth arrest in normal human mammary epithelial cells by establishing a block during mid-G(1) corresponding to the time when the retinoblastoma protein (Rb) would normally be inactivated by hyperphosphorylation. IFN gamma inhibits the kinase activities of cdk2, cdk4 and cdk6 within 24 h of treatment, Protein levels of the cdks and G(1) cyclins do not change within this time period, although cdk4 levels are significantly reduced by 48 h. IFN gamma treatment induces p27(Kip1) protein levels, presumably by a posttranscriptional mechanism as no change was observed in the mRNA levels. In addition, IFN gamma-induced inhibition of cdk2 and cyclin E-associated kinase activities is accompanied by a 4.5-fold or greater increase of p27(Kip1) in cdk2 complexes, p27 may also have a role in the inhibition of cdk4/6 kinase activities, as p27 protein associated with these complexes was increase by 55-70% after IFN gamma. In mammary carcinoma cell Lines which are resistant to growth inhibition by IFN gamma, p27 levels are not induced by IFN gamma nor is cdk2 kinase activity inhibited, despite high baseline levels of p27 in cdk2 complexes, However, exogenous expression of p27 in these cells induces growth arrest, In addition, purified p27 protein added to cdk2 complexes immunoprecipitated from carcinoma cells is able to inhibit the kinase activity in a dose dependent manner, Our results suggest that p27(Kip1) has a role in mediating IFN gamma-induced terminal growth arrest. Resistance of mammary carcinomas to growth inhibition by IFN gamma does not appear to involve resistance of cdk2 complexes to the action of p27, but rather an inability to appropriately regulate the balance of cdk2, cyclin E and p27 levels. C1 NIEHS,CELL BIOL SECT,PULM PATHOBIOL LAB,NIH,RES TRIANGLE PK,NC 27709. NCI,MED BREAST CANC SECT,MED BRANCH,NIH,BETHESDA,MD 20892. OI Jetten, Anton/0000-0003-0954-4445 NR 81 TC 60 Z9 61 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 1 PY 1997 VL 14 IS 17 BP 2111 EP 2122 DI 10.1038/sj.onc.1201055 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA WW809 UT WOS:A1997WW80900013 PM 9160891 ER PT J AU Wisniewski, SR Hammer, ME Grizzard, WS Kelsey, SF Everett, D Packo, KH Yarian, DL Doft, BH AF Wisniewski, SR Hammer, ME Grizzard, WS Kelsey, SF Everett, D Packo, KH Yarian, DL Doft, BH TI An investigation of the hospital charges related to the treatment of endophthalmitis in the endophthalmitis vitrectomy study SO OPHTHALMOLOGY LA English DT Article ID INTRAVITREAL VANCOMYCIN; ECONOMIC-ANALYSIS AB Purpose: The purpose of the study is to assess the hospital charges associated with the treatment of endophthalmitis using a sample of patients from the Endophthalmitis Vitrectomy Study (EVS). Methods: The Endophthalmitis Vitrectomy Study was a multicenter, randomized clinical trial with a two-by-two factorial design to compare immediate pars plana vitrectomy to tap-biopsy and to compare the use of systemic antibiotics (intravenous) to no intravenous antibiotics in the management of postoperative endophthalmitis. Hospital charge data were collected retrospectively from 129 patients from the 4 clinical centers participating in this ancillary study. This represents 31% of the total Endophthalmitis Vitrectomy Study population. An analysis of variance was used to compare hospital charges across center and treatment. A charge-effectiveness analysis compared measures the effectiveness across treatment groups. The annual savings of hospital charges in the United States was estimated for a range of annual incidence rates of endophthalmitis. Results: The use of intravenous antibiotics significantly increased hospital charges. Patients undergoing vitrectomy had significantly higher hospital charges than did patients undergoing tap-biopsy. The most charge-effective treatment for patients presenting with light perception only vision was immediate vitrectomy, whereas the most charge-effective treatment for patients presenting with better vision was tap-biopsy. Factors other than treatment independently associated with hospital charges were female sex, history of diabetes, symptom of red eye, and baseline vision of light perception only. Conclusions: Assuming the results of the Endophthalmitis Vitrectomy Study were used as a guide for the treatment of endophthalmitis, the estimated annual nationwide reduction of hospital charges would be between $7.6 million and $40.0 million. C1 UNIV PITTSBURGH,GRAD SCH PUBL HLTH,EPIDEMIOL DATA COORDINATING CTR,PITTSBURGH,PA. RETINA ASSOCIATES,TAMPA,FL. NEI,NIH,BETHESDA,MD 20892. RUSH MED COLL,ILLINOIS RETINA ASSOCIATES,CHICAGO,IL 60612. RETINA VITREOUS CTR PA,EDISON,NJ. OI Wisniewski, Stephen/0000-0002-3877-9860 FU NEI NIH HHS [EY08150, EY08151, EY08210] NR 16 TC 13 Z9 13 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 1997 VL 104 IS 5 BP 739 EP 745 PG 7 WC Ophthalmology SC Ophthalmology GA WY141 UT WOS:A1997WY14100012 PM 9160017 ER PT J AU Nader, PR Yang, MH Luepker, RV Parcel, GS Pirie, P Feldman, HA Stone, EJ Webber, LS AF Nader, PR Yang, MH Luepker, RV Parcel, GS Pirie, P Feldman, HA Stone, EJ Webber, LS TI Parent and physician response to children's cholesterol values of 200 mg/dL or greater: The child and adolescent trial for cardiovascular health experiment SO PEDIATRICS LA English DT Article DE children; elevated cholesterol; parental response; physician response ID UNITED-STATES; RISK-FACTORS; PEDIATRICIANS; LIPOPROTEIN; ATTITUDES; DISEASE AB Objective. To determine parental actions and concerns and physician responses to parental notification that a child's cholesterol value was 200 mg/dL or greater, a value recommended by the National Cholesterol Education Program to warrant physician follow-up and evaluation. Methodology. A telephone survey of parents (n = 784) and physicians (n = 117) was carried out after parental notification of a total blood cholesterol value obtained as part of measurement done while participating in the Child and Adolescent Trial for Cardiovascular Health in 96 schools located in California, Louisiana, Minnesota, and Texas. Results. Only 20% of parents contacted physicians. Factors associated with this action included whether the parent was notified once or twice, the level of the cholesterol, previous cholesterol testing in the parent, and medical insurance that covered the visit. Family history of cardiovascular disease, when other factors were considered, did not increase the likelihood that a physician contact would be made. After contact with the physician, 59% of physicians reported evaluating children for cholesterol; about half reported repeating the cholesterol determination. Conclusion. Parental knowledge of a child's cholesterol value of 200 mg/dL or greater did not result in substantially further seeking of health care. C1 UNIV CALIF SAN DIEGO, DEPT PEDIAT, LA JOLLA, CA 92093 USA. NEW ENGLAND RES INST, WATERTOWN, MA 02172 USA. UNIV MINNESOTA, SCH PUBL HLTH, DIV EPIDEMIOL, MINNEAPOLIS, MN 55455 USA. UNIV TEXAS, HLTH SCI CTR, SCH PUBL HLTH, CTR HLTH PROMOT RES & DEV, HOUSTON, TX USA. NHLBI, DIV EPIDEMIOL & CLIN APPLICAT, PREVENT SCI RES GRP, BETHESDA, MD 20892 USA. TULANE UNIV, SCH PUBL HLTH & TROP MED, NEW ORLEANS, LA USA. FU NHLBI NIH HHS [HL39870] NR 21 TC 9 Z9 9 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAY PY 1997 VL 99 IS 5 BP art. no. EP e5 DI 10.1542/peds.99.5.e5 PG 6 WC Pediatrics SC Pediatrics GA WX728 UT WOS:A1997WX72800015 PM 9113962 ER PT J AU Long, RM AF Long, RM TI What can NIH grantees do to increase the public's understanding of the institutes' roles in supporting biomedical research SO PHARMACEUTICAL RESEARCH LA English DT Editorial Material RP Long, RM (reprint author), NIGMS,PHARMACOL & PHYSIOL SCI BRANCH,DIV PHARMACOL PHYSIOL & BIOL CHEM,NIH,BETHESDA,MD, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD MAY PY 1997 VL 14 IS 5 BP 553 EP 553 PG 1 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA WZ847 UT WOS:A1997WZ84700001 ER PT J AU Baptista, T DeBaptista, EA Hernandez, L Altemus, M Weiss, SR AF Baptista, T DeBaptista, EA Hernandez, L Altemus, M Weiss, SR TI Tamoxifen prevents sulpiride-induced weight gain in female rats SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE neuroleptics; sulpiride; obesity; rats; tamoxifen; bromocriptine; estradiol ID BREAST-CANCER PATIENTS; BODY-WEIGHT; FOOD-INTAKE; PREMENOPAUSAL WOMEN; DOPAMINE-RECEPTORS; SYSTEMIC SULPIRIDE; ESTROGEN-RECEPTOR; PROLACTIN; SCHIZOPHRENIA; ANTIESTROGEN AB To evaluate its potential utility in counteracting neuroleptic-induced obesity, the effects of long-term administration of tamoxifen (TAM) on body weight (BW) and food intake (FI) of gonadalIy intact and sulpiride-treated (SUL) female rats were assessed. In addition, estradiol and prolactin serum levels were measured in rats treated with SUL, SUL plus TAM and SUL plus bromocriptine (BR). TAM, at doses of 10, 50 and 100 pg, significantly decreased BW gain; FI was significantly reduced at the doses of 50 and 100 mu g. In addition, doses of TAM ranging from 5-100 mu g completely prevented SUL-induced BW gain and hyperphagia. BR also prevented SUL effects on BW and FI. In contrast to BR, concomitant administration of TAM did not prevent SUL-induced hyperprolactinemia. Estradiol levels were not modified by SUL alone or SUL plus BR, but they were significantly increased in the animals treated with TAM plus SUL. Neuroleptic-induced obesity in female rats might be related to an alteration in gonadal steroid balance secondary to hyperprolactinemia. While BR might counteract neuroleptic-induced weight gain by preventing hyperprolactinemia, TAM might directly interact with estrogen receptors, or indirectly increase estradiol levels. The use of TAM in preventing neuroleptic-induced obesity in humans warrants further investigation. (C) 1997 Elsevier Science Inc. C1 UNIV LOS ANDES,SCH MED,DEPT PHYSIOL,MERIDA,VENEZUELA. NATL INST HLTH,BIOL PSYCHIAT BRANCH,BETHESDA,MD. UNIV LOS ANDES,SCH PHARM,DEPT MICROBIOL,MERIDA,VENEZUELA. NR 59 TC 28 Z9 28 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 MAY-JUN PY 1997 VL 57 IS 1-2 BP 215 EP 222 DI 10.1016/S0091-3057(96)00315-2 PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA XA088 UT WOS:A1997XA08800030 PM 9164575 ER PT J AU Piscitelli, SC Forrest, A Lush, RM Ryan, N Whitfield, LR Figg, WD AF Piscitelli, SC Forrest, A Lush, RM Ryan, N Whitfield, LR Figg, WD TI Pharmacometric analysis of the effect of furosemide on suramin pharmacokinetics SO PHARMACOTHERAPY LA English DT Article ID HTLV-III/LAV INFECTION; PROSTATE-CANCER; ADAPTIVE-CONTROL; PROBENECID INTERACTION; GROWTH-FACTOR; PHASE-I; DRUG; VARIABLES; CARCINOMA; DIURETICS AB Objective. To characterize the effects of furosemide on the pharmacokinetics of suramin, a renally eliminated investigational antineoplastic agent. Design. Retrospective population pharmacokinetic analysis. Setting. Government biomedical research facility. Patients. Twenty-six men with hormone-refractory prostate cancer and one with adrenocortical carcinoma. Interventions. Patients received suramin by continuous or intermittent infusion with and without concomitant furosemide. Measurements and Main Results. Optimum suramin regimens were achieved by adaptive feedback control, and pharmacokinetic data were collected both in the presence and absence of furosemide. Suramin concentrations were determined by high-performance liquid chromatography (coefficient of variation <8%). Suramin concentrations were fit to a three-compartment linear model with six coefficients and two rate inputs, which allowed furosemide to affect suramin pharmacokinetics. Individual and population parameter estimates were determined using the iterative two-stage approach. Concomitant furosemide was associated with a median decrease in total body clearance of suramin by 36% (range 0-63%, p<0.0001). No other parameter was significantly altered, and there was no trend for change in any pharmacokinetic value with time. Suramin plasma concentrations were simulated with and without prolonged furosemide therapy in 26 patients for 12 weeks. The average suramin concentration increased by greater than 33% in 12 patients; 2 patients had a greater than 67% increase in this extreme case model. Conclusion. Coadministration of furosemide with suramin can cause an increase in suramin concentrations; however, due to suramin's long half-life, its rate of accumulation is very slow. Nonetheless, in individuals receiving suramin by nonadaptive control, appropriate precautions should be taken when prolonged furosemide therapy is begun. C1 NCI, CLIN PHARMACOL BRANCH, CLIN PHARMACOKINET SECT, NIH, BETHESDA, MD 20892 USA. NIH, CLIN PHARMACOKINET RES LAB, CTR CLIN, DEPT PHARM, BETHESDA, MD 20892 USA. MILLARD FILLMORE HOSP, CLIN PHARMACOKINET LAB, PHARMACOMETR DIV, BUFFALO, NY 14209 USA. SUNY BUFFALO, BUFFALO, NY USA. WARNER LAMBERT PARKE DAVIS, PARKE DAVIS PHARMACEUT RES, PHARMACOKINET DRUG METAB SECT, ANN ARBOR, MI 48105 USA. RI Figg Sr, William/M-2411-2016 NR 47 TC 2 Z9 2 U1 0 U2 1 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD MAY-JUN PY 1997 VL 17 IS 3 BP 431 EP 437 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA XA090 UT WOS:A1997XA09000003 PM 9165547 ER PT J AU McCloud, TG Britt, JR Cartner, LK Pearl, KC Majadly, FD Muschik, GM Klueh, PA Cragg, GM Thomas, DW Jato, JG Simon, JE AF McCloud, TG Britt, JR Cartner, LK Pearl, KC Majadly, FD Muschik, GM Klueh, PA Cragg, GM Thomas, DW Jato, JG Simon, JE TI Quantitation of the anti-HIV alkaloids michellamines A and B by high pressure liquid chromatography SO PHYTOCHEMICAL ANALYSIS LA English DT Article; Proceedings Paper CT International Congress on Natural Products Research CY JUL 31-AUG 04, 1994 CL HALIFAX, CANADA DE Ancistrocladus; alkaloids; anti-HIV activity; michellamines; high pressure liquid chromatography ID ANCISTROCLADUS-ABBREVIATUS; FLUORESCENCE DETECTION; KORUPENSIS AB Michellamines A and B, naphthylisoquinoline dimeric alkaloids from the leaf of a previously undescribed species of the genus Ancistrocladus, show anti-human immunodeficiency virus (HIV) activity in an in vitro screen, In order to determine the distribution of these alkaloids in the genus, the level of production in the new species, and to gain an understanding of the horticultural aspects of production, a sensitive high pressure liquid chromatography analytical method requiring a small biomass was developed, This method resolved michellamines A and B and congeners and enabled quantitation of each, The production of the michellamines was found to be limited to the new species, A, korupensis. (C) 1997 by John Wiley & Sons, Ltd. C1 NCI,NIH,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. UNIV YAOUNDE 1,FAC MED & BIOMED SCI,YAOUNDE,CAMEROON. PURDUE UNIV,CTR NEW CROPS & PLANT PROD,W LAFAYETTE,IN 47907. RP McCloud, TG (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,POB B,FREDERICK,MD 21702, USA. NR 12 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0958-0344 J9 PHYTOCHEM ANALYSIS JI Phytochem. Anal. PD MAY-JUN PY 1997 VL 8 IS 3 BP 120 EP 123 DI 10.1002/(SICI)1099-1565(199705)8:3<120::AID-PCA345>3.3.CO;2-W PG 4 WC Biochemical Research Methods; Plant Sciences; Chemistry, Analytical SC Biochemistry & Molecular Biology; Plant Sciences; Chemistry GA WY859 UT WOS:A1997WY85900005 ER PT J AU Smith, EJ Lyons, LA Cheng, HH Suchyta, SP AF Smith, EJ Lyons, LA Cheng, HH Suchyta, SP TI Comparative mapping of the chicken genome using the East Lansing reference population SO POULTRY SCIENCE LA English DT Article DE synteny; polymerase chain reaction; comparative mapping; linkage; genes ID NUCLEOTIDE-SEQUENCE; CDNA CLONING; GENE; EXPRESSION; EMBRYO AB The annotation of known genes on Linkage maps provides an informative framework for synteny mapping. In comparative gene mapping, conserved synteny is broadly defined as groups of two or more Linked markers that are also Linked in two or more species. Although many anonymous markers have been placed on the chicken genome map, locating known genes will augment the number of conserved syntenic groups and consolidate linkage groups. In this report, 21 additional genes have been assigned to linkage soups or ckromosomes; five syntenic groups were identified. Ultimately, conserved syntenic groups may help to pinpoint important quantitative trait loci. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. RP Smith, EJ (reprint author), USDA ARS,AVIAN DIS & ONCOL LAB,3606 E MT HOPE RD,E LANSING,MI 48823, USA. NR 34 TC 18 Z9 18 U1 0 U2 2 PU POULTRY SCIENCE ASSOC INC PI SAVOY PA 1111 NORTH DUNLAP AVE, SAVOY, IL 61874 SN 0032-5791 J9 POULTRY SCI JI Poult. Sci. PD MAY PY 1997 VL 76 IS 5 BP 743 EP 747 PG 5 WC Agriculture, Dairy & Animal Science SC Agriculture GA WZ475 UT WOS:A1997WZ47500013 PM 9154628 ER PT J AU Adams, EM Kirkley, J Eidelman, G Dohlman, J Plotz, PH AF Adams, EM Kirkley, J Eidelman, G Dohlman, J Plotz, PH TI The predominance of beta (CC) chemokine transcripts in idiopathic inflammatory muscle diseases SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Article DE dermatomyositis; polymyositis; cytokines; inflammation ID POLYMERASE CHAIN-REACTION; CYTOKINE GENE-EXPRESSION; T-CELLS; RHEUMATOID-ARTHRITIS; ALVEOLAR MACROPHAGES; GROWTH-FACTOR; POLYMYOSITIS; MIP-1-ALPHA; RECEPTOR; PROTEIN-1-ALPHA AB Cytokines and chemokines that upregulate major histocompatibility complex class I antigens, recruit lymphocytes, and enhance T-cell-mediated myotoxicity may be important in the pathogenesis of dermatomyositis and polymyositis. We searched for cytokine and chemokine transcripts in inflammatory muscle specimens from 14 newly diagnosed or treated patients. Control specimens from six patients without inflammatory muscle disease were analyzed for transcripts of interleukins-1 beta, -2, -4, -6, -10, and -15, and interferon-gamma, tumor necrosis factor-alpha, transforming growth factor-beta(1), macrophage inflammatory proteins-1 alpha and -1 beta (MIP-1 alpha, MIP-1 beta), and the chemokine ''regulated on activation, normally T expressed and secreted'' (RANTES). Surprisingly, the proinflammatory and lymphocyte cytokines were detected only sporadically in myositis muscle specimens, and their presence did not correlate with disease activity or treatment status of the patient. In contrast, MIP-1 alpha and MIP-1 beta were detected in 13 and 6 myositis biopsies, respectively, and RANTES, another beta (CC) chemokine, was detected in eight myositis biopsies. This study and other reports of low levels of acute-phase cytokines in myositis patients suggest that the proinflammatory cytokines do not:play a major role in ongoing muscle dam age. The CC chemokines studied here, in particular MIP-1 alpha, might contribute to ongoing muscle inflammation, and the pathogenesis of inflammation in myositis may follow a previously unrecognized pathway. C1 KNOX COLL,DEPT BIOL,GALESBERG,IL. RP Adams, EM (reprint author), NIAMSD,ARTHRIT & RHEUMATISM BRANCH,NIH,B10-9N244,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 52 TC 41 Z9 42 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 1081-650X J9 P ASSOC AM PHYSICIAN JI Proc. Assoc. Am. Phys. PD MAY PY 1997 VL 109 IS 3 BP 275 EP 285 PG 11 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA WZ441 UT WOS:A1997WZ44100008 PM 9154644 ER PT J AU Kotake, S Schumacher, HR Yarboro, CH Arayssi, TK Pando, JA Kanik, KS Gourley, MF Klippel, JH Wilder, RL AF Kotake, S Schumacher, HR Yarboro, CH Arayssi, TK Pando, JA Kanik, KS Gourley, MF Klippel, JH Wilder, RL TI In vivo gene expression of type 1 and type 2 cytokines in synovial tissues from patients in early stages of rheumatoid, reactive, and undifferentiated arthritis SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Article; Proceedings Paper CT 59th National Scientific Meeting of the American-College-of-Rheumatology CY OCT 21-26, 1995 CL SAN FRANCISCO, CA SP Amer Coll Rheumatol DE nested RT-PCR; Chlamydia trachomatis; interleuken-15; type 1 helper T cell; type 2 helper T cell ID POLYMERASE CHAIN-REACTION; CELL GROWTH-FACTOR; T-CELL; MESSENGER-RNA; INTERLEUKIN-10 PRODUCTION; INFLAMMATORY ARTHRITIS; MONONUCLEAR-CELLS; NESTED PRIMERS; IL-2 RECEPTOR; RECENT-ONSET AB It has been reported that the mRNA of the type 1 cytokine, interferon-gamma (IFN-gamma)-but not the type 2 cytokine interleukin-4 (IL-4)-is detected in synovial tissues of rheumatoid arthritis (RA) patients, whereas both IFN-gamma and IL-4 mRNA are detected in reactive arthritis (ReA). To evaluate such data more extensively, we obtained 208 synovial specimens in a prospective study of 52 early synovitis patients (13 RA, II ReA, 28 undifferentiated oligoarthropathy) and analyzed type 1 and type 2 cytokine mRNA expression in specimens containing sufficient mRNA. Using a nested reverse transcriptase polymerase chain reaction technique, we measured the relative mRNA levels of 10 cytokines and CD3 delta chain. We detected IL-10, IL-15, and CD3 delta chain mRNA in all RA and ReA patients and frequently detected tumor necrosis factor-alpha, IL-1 beta, and IFN-gamma mRNA. IL-6 and IL-12 p40 mRNA were detected in approximately one-half of the patients. We also detected greater amounts of IL-2 and IFN-gamma mRNA in ReA than were detected in RA. However, we rarely detected IL-4 or IL-13 mRNA. Similar cytokine profiles were observed in undifferentiated oligoarthropathy. The amounts of cytokine mRNAs, except for IL-10, in specimens from the patients taking prednisone or second-line antirheumatic drugs tended to be less than in specimens from the patients taking neither prednisone nor second-line antirheumatic drugs. These results suggest that cytokine mRNA profiles in patients with RA, ReA, and undifferentiated arthritis in their early stages are skewed toward proinflammatory macrophage-derived and type 1 cytokines. IL-10-not IL-4 or IL-13-mRNA appears to be the major antiinflammatory cytokine mRNA. Drug therapy is associated with depressed proinflammatory and type 1 cytokine mRNA production. The differences in the expression of IL-2 and IFN-gamma mRNA between RA and ReA may reflect unique etiological or host factors associated with the early stages of these diseases. C1 NIAMSD,ARB,NIH,BETHESDA,MD 20892. UNIV PENN,PHILADELPHIA,PA 19104. OI Arayssi, Thurayya/0000-0003-2469-0272 NR 68 TC 64 Z9 66 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 1081-650X J9 P ASSOC AM PHYSICIAN JI Proc. Assoc. Am. Phys. PD MAY PY 1997 VL 109 IS 3 BP 286 EP 301 PG 16 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA WZ441 UT WOS:A1997WZ44100009 PM 9154645 ER PT J AU Djonov, V Ball, RK Graf, S Mottaz, AE Arnold, AM Flanders, K Studer, UE Merz, VW AF Djonov, V Ball, RK Graf, S Mottaz, AE Arnold, AM Flanders, K Studer, UE Merz, VW TI Transforming growth factor-beta 3 is expressed in nondividing basal epithelial cells in normal human prostate and benign prostatic hyperplasia, and is no longer detectable in prostate carcinoma SO PROSTATE LA English DT Article DE TGF-beta; proliferation; prostate; carcinoma ID FACTOR-BETA; MESSENGER-RNA; ADULT TISSUES; CANCER; ADENOCARCINOMA; PROLIFERATION; MOUSE; CDNA; RAS; GROWTH-FACTOR-BETA-1 AB BACKGROUND. We investigated the role of the transforming growth factor beta (T METHODS. Expression of TGF-beta mRNA was measured by Northern blot analysis of tissue extracts, and TGF-beta protein by immunohistochemical analysis of tissue sections. Proliferating cells were detected by their expression of Ki-67 antigen. RESULTS. The level of TGF-beta 1 mRNA was equal among normal prostate, benign prostatic hyperplasia (BPH), and prostate carcinoma. TGF-beta 2 mRNA was not detectable, and TGF-beta 3 mRNA was expressed 20-fold lesion in carcinoma compared to BPH and normal prostate. TGF-beta 1 protein was expressed in the stromal cells in all three tissues and TGF-beta 3 protein in the basal layer of epithelial cells, but not in carcinoma. Proliferating epithelial cells fail to express TGF-beta 3. CONCLUSIONS. TGF-beta 1 and TGF-beta 3 are independently regulated, and carcinoma of the prostate is characterized by the loss of basal epithelial cells expressing TGF-beta 3. (C) 1997 Wiley-Liss, Inc. C1 UNIV BERN, DEPT CLIN & EXPT RES, CH-3004 BERN, SWITZERLAND. UNIV BERN, INSELSPITAL, DEPT UROL, CH-3010 BERN, SWITZERLAND. NCI, CHEMOPREVENT LAB, BETHESDA, MD 20892 USA. NR 47 TC 23 Z9 23 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 0270-4137 J9 PROSTATE JI Prostate PD MAY 1 PY 1997 VL 31 IS 2 BP 103 EP 109 PG 7 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA WW196 UT WOS:A1997WW19600005 PM 9140123 ER PT J AU Lin, ZL Shenker, A Pearlstein, R AF Lin, ZL Shenker, A Pearlstein, R TI A model of the lutropin/choriogonadotropin receptor: Insights into the structural and functional effects of constitutively activating mutations SO PROTEIN ENGINEERING LA English DT Article DE glycoprotein hormone receptors; G-protein coupled receptors; molecular modeling; receptor activation; transmembrane helices ID PROTEIN-COUPLED RECEPTORS; SITE-DIRECTED MUTAGENESIS; PROJECTION STRUCTURE; PROLINE RESIDUES; HELIX; RHODOPSIN; BACTERIORHODOPSIN; PREDICTION; OPSIN AB A model of the seven transmembrane helical domain (7-TM) of the human lutropin receptor was constructed from the 2D electron density map of bovine rhodopsin and a set of geometric parameters derived from a published analysis of 204 G-protein coupled receptor sequences. The Self-Consistent Ensemble Optimization method was applied to predict overall side chain packing. The model is consistent with the general helical packing properties expected of transmembrane proteins and suggests possible structural and functional effects of constitutively activating mutations. A tightly packed hydrophobic cluster formed between the intracellular halves of TM5 and TM6, as well as a specific H-bonding network formed between the central regions of TM6 and TM7, is proposed to be critical for stabilizing the inactive form of the receptor. The model suggests that single activating mutations perturb the specific interactions of TM6 with TM5 and TM7, either by disrupting the hydrophobic packing between TM5 and TM6, or by weakening the H-bonds between TM6 and TM7. C1 NIH,CTR MOL MODELING,STRUCT BIOL LAB,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. NORTHWESTERN UNIV,SCH MED,CHILDRENS MEM HOSP,DIV ENDOCRINOL,CHICAGO,IL 60614. NR 55 TC 64 Z9 64 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD MAY PY 1997 VL 10 IS 5 BP 501 EP 510 DI 10.1093/protein/10.5.501 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA XF720 UT WOS:A1997XF72000006 PM 9215568 ER PT J AU Hickman, AB Dyda, F Craigie, R AF Hickman, AB Dyda, F Craigie, R TI Heterogeneity in recombinant HIV-1 integrase corrected by site-directed mutagenesis: The identification and elimination of a protease cleavage site SO PROTEIN ENGINEERING LA English DT Article DE Escherichia coli; HIV; integrase; protease; site-directed mutagenesis ID VIRUS TYPE-1 INTEGRASE; CATALYTIC DOMAIN; ESCHERICHIA-COLI; RESIDUES; INVITRO AB Purified recombinant human immunodeficiency virus type 1 (HIV-1) integrase and certain deletion mutants exhibit heterogeneity consistent with proteolysis at a site close to the C-terminus. Electrospray ionization mass spectrometric analysis indicated that proteolytic cleavage generated a protein missing five residues from the C-terminus, PCR mutagenesis of amino acids on either side of the cleavage site identified two changes which were subsequently shown to prevent clipping when proteins were expressed and purified from Escherichia coli: the substitution of Arg284, the residue on the C-terminal side of the cleavage site, by either glycine or lysine, The introduction of either of these mutations into full-length integrase did not affect in vitro 3' processing or strand transfer activities, Thus, the incorporation of either of these mutations is likely to be beneficial when homogeneity of HIV-1 integrase is a concern, as in crystallographic or nuclear magnetic resonance spectroscopic experiments. C1 NIDDKD, MOL BIOL LAB, NIH, BETHESDA, MD 20892 USA. NR 16 TC 3 Z9 3 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD MAY PY 1997 VL 10 IS 5 BP 601 EP 606 DI 10.1093/protein/10.5.601 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA XF720 UT WOS:A1997XF72000017 PM 9215579 ER PT J AU Onken, LS Blaine, JD AF Onken, LS Blaine, JD TI Behavioral therapy development and psychological science: Reinforcing the bond SO PSYCHOLOGICAL SCIENCE LA English DT Article; Proceedings Paper CT Workshop on Behavioral Therapy Development and Psychological Science CY MAY 14-16, 1996 CL BETHESDA, MD SP NIH NIDA ID SCIENTIST AB An abundance of research from diverse areas of psychological science is potentially relevant to behavioral therapy development research. The National Institute on Drug Abuse of the National Institutes of Health convened a workshop to reinforce the connection between basic behavioral and therapy development research. The articles in this Special Section are the product of this workshop. Several lines of basic behavioral research are described, and implications for the development of behavioral therapies are discussed. This Special Section highlights the notion that strengthening the bond between behavioral therapy development research and basic behavioral science will accelerate the advancement of knowledge about behavior, behavioral change, and therapeutic interventions. RP Onken, LS (reprint author), NIDA,NIH,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 3 TC 3 Z9 3 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0956-7976 J9 PSYCHOL SCI JI Psychol. Sci. PD MAY PY 1997 VL 8 IS 3 BP 143 EP 144 DI 10.1111/j.1467-9280.1997.tb00397.x PG 2 WC Psychology, Multidisciplinary SC Psychology GA WZ239 UT WOS:A1997WZ23900001 ER PT J AU AlAbsi, M Bongard, S Buchanan, T Pincomb, GA Licinio, J Lovallo, WR AF AlAbsi, M Bongard, S Buchanan, T Pincomb, GA Licinio, J Lovallo, WR TI Cardiovascular and neuroendocrine adjustment to public speaking and mental arithmetic stressors SO PSYCHOPHYSIOLOGY LA English DT Article DE interpersonal stress; public speaking; cortisol; ACTH; blood pressure; hemodynamic adjustment ID AMBULATORY BLOOD-PRESSURE; BEHAVIORAL STRESSORS; ADRENOCORTICAL RESPONSES; INTERPERSONAL INFLUENCE; SOCIAL STRESS; HEART-RATE; REACTIVITY; DISEASE; TASK; HYPERTENSIVES AB In this study, we evaluated cardiovascular, neuroendocrine, and psychological adjustment to repeated presentations of a public speaking and a mental arithmetic task. Brief versions of mental arithmetic tasks have been used widely in previous reactivity studies, and growing attention to more socially salient tasks has led to the increased use of public speaking tasks. However, psychophysiological adjustment during extended and repeated exposure to these tasks has not been delineated. In the present study, 52 healthy men worked on three 8-min presentations of public speaking and of mental arithmetic in a repeated measure design. Both tasks produced substantial cardiovascular, adrenocorticotropic hormone, and cortisol responses; public speaking produced greater changes. Repeated presentations of public speaking produced a stable pattern of cardiac activation, whereas repetitions of the mental arithmetic initially produced large cardiac responses that changed to a more vascular tonus across task periods. Both tasks increased negative moods. However, correlations between the endocrine, cardiovascular, and negative moods were significant only during the public speaking stressor. The public speaking task is a socially relevant experimental protocol for studying reactivity in the laboratory setting and elicits relatively high, stable, and homogeneous responses. C1 NIMH, BETHESDA, MD 20892 USA. RP AlAbsi, M (reprint author), VET AFFAIRS MED CTR, BEHAV SCI LABS, 151A, 921 NE 13TH ST, OKLAHOMA CITY, OK 73104 USA. RI Licinio, Julio/L-4244-2013; OI Licinio, Julio/0000-0001-6905-5884; Buchanan, Tony/0000-0002-9166-8457 NR 51 TC 251 Z9 253 U1 7 U2 35 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD MAY PY 1997 VL 34 IS 3 BP 266 EP 275 DI 10.1111/j.1469-8986.1997.tb02397.x PG 10 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA XA978 UT WOS:A1997XA97800003 PM 9175441 ER PT J AU Schechter, AN AF Schechter, AN TI Sickle cell anemia - Reply SO PUBLIC HEALTH REPORTS LA English DT Letter RP Schechter, AN (reprint author), NIDDKD,BIOL CHEM LAB,NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD MAY-JUN PY 1997 VL 112 IS 3 BP 177 EP 177 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WZ466 UT WOS:A1997WZ46600002 ER PT J AU Sherman, S AF Sherman, S TI The False Claims Act: Litigating scientific misconduct .2. SO PUBLIC HEALTH REPORTS LA English DT Article RP Sherman, S (reprint author), NIH,NATL INST HLTH BRANCH,PUBL HLTH DIV,OFF GEN COUNSEL,DHHS,RM 2B-50,BLDG 31,31 CENTER DR,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD MAY-JUN PY 1997 VL 112 IS 3 BP 248 EP 248 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WZ466 UT WOS:A1997WZ46600038 PM 9182306 ER PT J AU Tekkel, M Rahu, M Veidebaum, T Hakulinen, T Auvinen, A Rytomaa, T Inskip, PD Boice, JD AF Tekkel, M Rahu, M Veidebaum, T Hakulinen, T Auvinen, A Rytomaa, T Inskip, PD Boice, JD TI The Estonian study of Chernobyl cleanup workers .1. Design and questionnaire data SO RADIATION RESEARCH LA English DT Article ID FREQUENCY; ACCIDENT AB Nearly 2% of the male population of Estonia aged 20-39 years were sent to Chernobyl to assist in the cleanup activities after the reactor accident. A cohort of 4,833 cleanup workers was assembled based on multiple and independent sources of information. Information obtained from 3,704 responses to a detailed questionnaire indicated that 63% of the workers were sent to Chernobyl in 1986; 54% were of Estonian and 35% of Russian ethnicity; 72% were married, and 1,164 of their 5,392 children were conceived after the Chernobyl disaster. The workers were less educated than their counterparts in the general population of Estonia, and only 8.5% had attended university, Based on doses entered in worker records, the mean dose was 11 cGy, with only 1.4% over 25 cGy. Nearly 85% of the workers were sent as part of military training activities, and more than half spent in excess of 3 months in the Chernobyl area. Thirty-six percent of the workers reported having worked within the immediate vicinity of the accident site; 11.5% worked on the roofs near the damaged reactor, clearing the highly radioactive debris, The most commonly performed task was the removal and burial of topsoil (55% of the workers), Potassium iodide was given to over 18% of the men. The study design also incorporates biological indicators of exposure based on the glycophorin A mutational assay of red blood cells and chromosome translocation analyses of lymphocytes; record linkage with national cancer registry and mortality registry files to determine cancer incidence and cause-specific mortality; thyroid screening examinations with ultrasound and fine-needle biopsy; and cryopreserved white blood cells and plasma for future molecular studies. Comprehensive studies of Chernobyl cleanup workers have potential to provide new information about cancer risks due to protracted exposures to ionizing radiation. (C) 1997 by Radiation Research Society. C1 INST CLIN & EXPT MED, DEPT EPIDEMIOL & BIOSTAT, EE-0016 TALLINN, ESTONIA. FINNISH CANC REGISTRY, FIN-00170 HELSINKI, FINLAND. KAROLINSKA INST, CANC EPIDEMIOL UNIT, S-17176 STOCKHOLM, SWEDEN. FINNISH CTR RADIAT & NUCL SAFETY, FIN-00101 HELSINKI, FINLAND. NATL CANC INST, RADIAT EPIDEMIOL BRANCH, BETHESDA, MD 20852 USA. RI Rahu, Mati/A-9981-2008 FU NCI NIH HHS [N01-CP-85638-03] NR 21 TC 18 Z9 19 U1 0 U2 2 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 EI 1938-5404 J9 RADIAT RES JI Radiat. Res. PD MAY PY 1997 VL 147 IS 5 BP 641 EP 652 DI 10.2307/3579631 PG 12 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA WY053 UT WOS:A1997WY05300014 PM 9146710 ER PT J AU Rahu, M Tekkel, M Veidebaum, T Pukkala, E Hakulinen, T Auvinen, A Rytomaa, T Inskip, PD Boice, JD AF Rahu, M Tekkel, M Veidebaum, T Pukkala, E Hakulinen, T Auvinen, A Rytomaa, T Inskip, PD Boice, JD TI The Estonian study of Chernobyl cleanup workers .2. Incidence of cancer and mortality SO RADIATION RESEARCH LA English DT Article ID CONSEQUENCES; RADIATION; FREQUENCY; ACCIDENT; HEALTH; LOCUS AB A cohort of 4,742 men from Estonia who had participated in the cleanup activities in the Chernobyl area sometime between 1986 and 1991 and were followed through 1993 was analyzed with respect to the incidence of cancer and mortality. Incidence and mortality in the cleanup workers were assessed relative to national rates. No increases were found in all cancers (25 incident cases compared to 26.5 expected) or in leukemia (no cases observed, 1.0 expected). Incidence did not differ statistically significantly from expectation for any individual cancer site or type, though lung cancer and non-Hodgkin's lymphoma both occurred slightly more often than expected. A total of 144 deaths were observed [standardized mortality ratio (SMR) = 0.98; 95% confidence interval (CI) = 0.82-1.14] during an average of 6.5 years of follow-up. Twenty-eight deaths (19.4%) were suicides (SMR = 1.52; 95% CI = 1.01-2.19), Exposure to ionizing radiation while at Chernobyl has not caused a detectable increase in the incidence of cancer among cleanup workers from Estonia, At least for the short follow-up period, diseases directly attributable to radiation appear to be of relatively minor importance when compared with the substantial excess of deaths due to suicide. (C) 1997 by Radiation Research Society. C1 FINNISH CANC REGISTRY,FIN-00170 HELSINKI,FINLAND. KAROLINSKA INST,CANC EPIDEMIOL UNIT,S-17176 STOCKHOLM,SWEDEN. FINNISH CTR RADIAT & NUCL SAFETY,FIN-00101 HELSINKI,FINLAND. NCI,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20852. RP Rahu, M (reprint author), INST CLIN & EXPT MED,DEPT EPIDEMIOL & BIOSTAT,HIIU 42,EE-0016 TALLINN,ESTONIA. RI Rahu, Mati/A-9981-2008; OI Auvinen, Anssi/0000-0003-1125-4818 FU NCI NIH HHS [N01-CP-85638-03] NR 28 TC 42 Z9 42 U1 0 U2 3 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD MAY PY 1997 VL 147 IS 5 BP 653 EP 657 DI 10.2307/3579632 PG 5 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA WY053 UT WOS:A1997WY05300015 PM 9146711 ER PT J AU Contoreggi, CS Jones, SW Lange, WR Meyer, WA AF Contoreggi, CS Jones, SW Lange, WR Meyer, WA TI Evaluation of HIV1 infection status by HIV1 PCR and culture methodologies in a small cohort of intravenous drug users SO RESEARCH IN VIROLOGY LA English DT Article DE HIV; PCR; viral load; infection status; intravenous drug users; Baltimore ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; BLOOD MONONUCLEAR-CELLS; PERIPHERAL-BLOOD; OLIGONUCLEOTIDE PROBES; PROVIRAL DNA; VIRAL BURDEN; AMPLIFICATION; INDIVIDUALS; QUANTITATION AB A small cohort of high-risk intravenous drug users (IVDU) from the Baltimore, MD, area was evaluated for HIV1 infection status and viral load, Quantitative dilution endpoint HIV1 DNA polymerase chain reaction (PCR) results, from HIV proviral DNA from quantitated peripheral blood mononuclear cell (PBMC) lysates, were compared to the dilution endpoint results for HIV PBMC micrococulture, The quantitative dilution endpoint HIV1 PCR was more rapid, sensitive and reproducible. In addition, an HIV1 capture RT-PCR technique was used to qualitatively detect the presence or absence of intact HIV1 virus in IVDU plasma and was compared with plasma culture detection, for HIV1 viraemia. Using the results of the PCR techniques, a rapid molecular assessment of the HIV1 infection status can be attained, which is important, as the IVDU population can be difficult to study prospectively. The PCR techniques can also be used to assess HIV1 burden as well as the potential effectiveness of antiviral therapies. These molecular techniques can be used to monitor the progression of HIV in patients and to evaluate the clinical effects of concurrent substance abuse. C1 MICROBIOL ASSOCIATES INC,ROCKVILLE,MD 20850. MARYLAND MED LABS INC,BALTIMORE,MD 21227. RP Contoreggi, CS (reprint author), NIDA,NIH,IRP,MOL NEUROBIOL BRANCH,POB 5180,BALTIMORE,MD 21224, USA. NR 28 TC 1 Z9 1 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 141 RUE JAVEL, 75747 PARIS, FRANCE SN 0923-2516 J9 RES VIROLOGY JI Res. Virol. PD MAY-JUN PY 1997 VL 148 IS 3 BP 215 EP 224 DI 10.1016/S0923-2516(97)83991-X PG 10 WC Virology SC Virology GA XD690 UT WOS:A1997XD69000003 PM 9201812 ER PT J AU QuintanillaMartinez, L Gamba, G AF QuintanillaMartinez, L Gamba, G TI Molecular biology in medicine .9. In situ hybridization. SO REVISTA DE INVESTIGACION CLINICA LA French DT Article RP QuintanillaMartinez, L (reprint author), NCI,DEPT PATHOL,NIH,BETHESDA,MD 20892, USA. NR 6 TC 3 Z9 3 U1 0 U2 0 PU INST NACIONAL NUTRICION PI TLALPAN PA VASCO DE QUIROZA #15, TLALPAN 14000 D F, MEXICO SN 0034-8376 J9 REV INVEST CLIN JI Rev. Invest. Clin. PD MAY-JUN PY 1997 VL 49 IS 3 BP 255 EP 258 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA XT740 UT WOS:A1997XT74000015 PM 9380980 ER PT J AU Segal, BH Sneller, MC AF Segal, BH Sneller, MC TI Infectious complications of immunosuppressive therapy in patients with rheumatic diseases SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; PNEUMOCYSTIS-CARINII PNEUMONIA; CENTRAL-NERVOUS-SYSTEM; WEGENERS GRANULOMATOSIS; CYCLOPHOSPHAMIDE TREATMENT; METHOTREXATE THERAPY; LEUKOCYTE KINETICS; ARTHRITIS; PREDNISONE; CELLS AB Infection continues to be a major cause of morbidity and mortality in patients with rheumatic diseases. The recognition and treatment of infections in these patients is a particularly difficult task because the spectrum of potential pathogens is broad and the clinical manifestations of infection often mimic those of the underlying rheumatic disease. This article presents a general overview of the immunosuppressive properties of agents commonly used in the treatment of rheumatic diseases and focuses on specific pathogens associated with different immunosuppressive regimens. Also provided is a framework for the diagnostic evaluation and treatment of various infectious syndromes in patients with rheumatic diseases. C1 NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. NR 93 TC 61 Z9 67 U1 2 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD MAY PY 1997 VL 23 IS 2 BP 219 EP & DI 10.1016/S0889-857X(05)70327-6 PG 20 WC Rheumatology SC Rheumatology GA WY406 UT WOS:A1997WY40600002 PM 9156390 ER PT J AU Langford, CA VanWaes, C AF Langford, CA VanWaes, C TI Upper airway obstruction in the rheumatic diseases SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Review ID SYSTEMIC LUPUS-ERYTHEMATOSUS; LARYNGEAL NERVE PALSY; HYPOCOMPLEMENTEMIC URTICARIAL VASCULITIS; WEGENERS GRANULOMATOSIS; CRICOARYTENOID ARTHRITIS; SJOGRENS-SYNDROME; RELAPSING POLYCHONDRITIS; HEREDITARY ANGIOEDEMA; SUBGLOTTIC STENOSIS; ACUTE EPIGLOTTITIS AB The upper airway is a complex structure that can be affected in a number of ways in patients with rheumatic diseases. Respiration is maintained through the upper airway; therefore, any obstruction to this passage is a potentially life-threatening event. Although airway obstruction can be effectively managed, suspicion for the diagnosis is necessary prior to initiating the appropriate care. This article reviews the mechanisms of airway obstruction, its symptoms and evaluation, and the specific upper airway manifestations that can occur in patients with rheumatic diseases. C1 NIDOCD,HEAD & NECK SURG BRANCH,NIH,BETHESDA,MD. RP Langford, CA (reprint author), NIAID,IMMUNOREGULAT LAB,NIH,BLDG 10,ROOM 11B-13,BETHESDA,MD 20892, USA. NR 125 TC 10 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD MAY PY 1997 VL 23 IS 2 BP 345 EP & DI 10.1016/S0889-857X(05)70334-3 PG 20 WC Rheumatology SC Rheumatology GA WY406 UT WOS:A1997WY40600009 PM 9156397 ER PT J AU Ellenberg, JH Gail, MH Geller, NL AF Ellenberg, JH Gail, MH Geller, NL TI Conversations with NIH statisticians: Interviews with the pioneers of biostatistics at the United States National Institutes of Health SO STATISTICAL SCIENCE LA English DT Article ID METHODOLOGICAL DEVELOPMENTS; CLINICAL-TRIALS; OF-HEALTH C1 NCI,BIOSTAT BRANCH,DIV CANC EPIDEMIOL & GENET,NIH,ROCKVILLE,MD 20892. NHLBI,OFF BIOSTAT RES,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. RP Ellenberg, JH (reprint author), WESTAT CORP,ROCKVILLE,MD 20850, USA. NR 14 TC 5 Z9 5 U1 1 U2 1 PU INST MATHEMATICAL STATISTICS PI HAYWARD PA IMS BUSINESS OFFICE-SUITE 6 3401 INVESTMENT BLVD, HAYWARD, CA 94545 SN 0883-4237 J9 STAT SCI JI Stat. Sci. PD MAY PY 1997 VL 12 IS 2 BP 77 EP 81 PG 5 WC Statistics & Probability SC Mathematics GA XT268 UT WOS:A1997XT26800001 ER PT J AU Gail, MH AF Gail, MH TI A conversation with Nathan Mante SO STATISTICAL SCIENCE LA English DT Article ID TABLES AB Nathan Mantel was born on February 16, 1919, in New York City. He received a B.S. degree in statistics from the City College of New York in 1939 and an M.A. degree from American University in 1956. He is a Fellow of the American Statistical Association and the Institute of Mathematical Statistics, has been elected Fellow of the Royal Statistical Society (RSS) and was recently made an Honorary Fellow of the RSS. He is also an elected member of the International Statistical Institute and a Fellow of the American Association for the Advancement of Science. He has been President of the Eastern North American Region of the Biometric Society and a member of the Council of the International Biometric Society. He has served on the editorial boards of Risk Analysis, Biometrics, Journal of the National Cancer Institute and Cancer Research. His tenure at the National Institutes of Health (NIH) included the years 1947-1974. This time was spent entirely as a mathematical statistician at the National Cancer Institute. While at NIH, he also held the position of Adjunct Professor of Biostatistics, Graduate School of Public Health, University of Pittsburgh. He was a recipient of the Superior Service Award, one of the highest civilian awards given by NIH. Since leaving NIH, he has been a Research Professor of Statistics at George Washington University and currently holds the title of Research Professor of Statistics at American University. Concurrently, from 1984 through 1990, he was Visiting Professor, Neuroepidemiology, at Temple University School of Medicine. RP Gail, MH (reprint author), NCI,BIOSTAT BRANCH,DIV CANC EPIDEMIOL & GENET,NIH,ROCKVILLE,MD 20892, USA. NR 23 TC 3 Z9 3 U1 1 U2 2 PU INST MATHEMATICAL STATISTICS PI HAYWARD PA IMS BUSINESS OFFICE-SUITE 6 3401 INVESTMENT BLVD, HAYWARD, CA 94545 SN 0883-4237 J9 STAT SCI JI Stat. Sci. PD MAY PY 1997 VL 12 IS 2 BP 88 EP 97 PG 10 WC Statistics & Probability SC Mathematics GA XT268 UT WOS:A1997XT26800003 ER PT J AU Simon, RM AF Simon, RM TI A conversation with Marvin A. Schneiderman SO STATISTICAL SCIENCE LA English DT Article AB Marvin A. Schneiderman was born on December 25, 1918, in Brooklyn, New York. He received a B.S. degree in mathematics and statistics from the City College of New York in 1939, an M.S. degree in statistics from American University in 1953 and a Ph.D. in statistics from American University in 1961. Additional graduate training and research was done at Ohio State University, Harvard Graduate School of Business and the London School of Hygiene and Tropical Medicine. He is a Fellow of the American Statistical Association and of the American Association for the Advancement of Science. He is also an elected member of the International Statistical Institute, an elected Fellow of the Royal Statistical Society and a Founding Member of the American Society of Preventive Oncology. He has served as President of the Washington Statistical Society, as Chairman of the Committee on Presidents of Statistical Societies, as a member of the Board of Directors of the American Statistical Association and as a Council member of the International Biometric Society. He has been an editor on the editorial advisory boards of several journals, including Cancer Research, Statistics in Medicine, Blood, Journal of the National Cancer Institute and the American Journal of Industrial Medicine. He was at the National Cancer Institute from 1948 through 1980. He began as a consulting statistician, then was appointed Head of the Controlled Trials Group for Cancer Chemotherapy and later became Associate Director for Field Studies and Statistics. His last appointment at NIH was as NCI Associate Director for Science Policy. He was awarded two of the highest honors accorded civilian employees at the NIH, the Distinguished Service Award and the Superior Service Award. After leaving the National Institutes of Health, he spent a short time with a private consulting firm with strong environmental interests. He then served as a fellow at the Environmental Law Institute before joining the National Research Council/National Academy of Sciences Board on Environmental Studies and Toxicology. He officially retired in 1995. Marvin Schneiderman passed away on April 1, 1997. RP Simon, RM (reprint author), NCI,BIOMETR RES BRANCH,DIV CANC TREATMENT DIAG & CTR,BETHESDA,MD 20852, USA. NR 5 TC 1 Z9 1 U1 1 U2 2 PU INST MATHEMATICAL STATISTICS PI HAYWARD PA IMS BUSINESS OFFICE-SUITE 6 3401 INVESTMENT BLVD, HAYWARD, CA 94545 SN 0883-4237 J9 STAT SCI JI Stat. Sci. PD MAY PY 1997 VL 12 IS 2 BP 98 EP 102 PG 5 WC Statistics & Probability SC Mathematics GA XT268 UT WOS:A1997XT26800004 ER PT J AU Hankey, B AF Hankey, B TI A conversation with William M. Haenszel SO STATISTICAL SCIENCE LA English DT Article AB William M. Haenszel was born on June 19, 1910, in Rochester, New York. He received a B.A. degree in 1931 and an M.A. degree in 1932, both from the University of Buffalo. He is an elected Fellow of the American Statistical Association, the American Public Health Association and the American Association For the Advancement of Science. He has been awarded a Doctor Honoris Causa en Salud Publica from the Universidad del Valle in Colombia. He has held positions as Secretary of the Statistics Section and member of the governing Council of the American Public Health Association, Chair of the Biometrics Section of the American Statistical Association and member of the Regional Advisory Board of the Eastern North Atlantic Region of the International Biometric Society. During his tenure at the National Institutes of Health (NIH) from 1952 through 1976, he served as Head of the Biometric Section and the Chief of the Biometry Branch at the National Cancer Institute. Since leaving the National Institutes of Health he was on staff at the Illinois Cancer Council, Professor of Epidemiology at the University of Illinois (he is currently Professor Emeritus) and a consultant to the World Health Organization. RP Hankey, B (reprint author), NCI,CANC STAT BRANCH,CANC CONTROL RES PROGRAM,DIV CANC PREVENT & CONTROL,NIH,ROCKVILLE,MD 20892, USA. NR 5 TC 0 Z9 0 U1 3 U2 3 PU INST MATHEMATICAL STATISTICS PI HAYWARD PA IMS BUSINESS OFFICE-SUITE 6 3401 INVESTMENT BLVD, HAYWARD, CA 94545 SN 0883-4237 J9 STAT SCI JI Stat. Sci. PD MAY PY 1997 VL 12 IS 2 BP 108 EP 112 PG 5 WC Statistics & Probability SC Mathematics GA XT268 UT WOS:A1997XT26800006 ER PT J AU Geller, NL Gordon, T AF Geller, NL Gordon, T TI A conversation with Tavia Gordon SO STATISTICAL SCIENCE LA English DT Editorial Material AB Tavia Gordon was born on December 14, 1917, in Chicago, Illinois. He received a B.A. degree in anthropology from the University of California in 1938. He did graduate work in anthropology at the University of Chicago in 1938-1939, in mathematics at the University of Southern California in 1947-1948, and in mathematical statistics at the University of California, Berkeley, in 1948-1950. He is a Fellow of the American Statistical Association and the Council on Epidemiology, American Heart Association. His tenure at NIH included the years 1954-1960 and 1966-1977, beginning as an Analytical Statistician with the Biometrics Research Section of the National Heart Institute. He spent the next two years at the Biometry Branch at the National Cancer Institute. His last 10 years at NIH were spent at the National Heart, Lung and Blood Institute. During this period he was heavily involved in the development of the design and analysis of the first long-term, large-scale community-based follow-up study in the United States, the Framingham Study. He was awarded the NIH Director's Award in 1977. Since leaving the National Institutes of Health, he has been a consulting statistician, a senior scientist for General Electric Corporation and, since 1981, a Research Professor at George Washington University Biostatistics Center. C1 GE CO,FAIRFIELD,CT 06431. GEORGE WASHINGTON UNIV,CTR BIOSTAT,WASHINGTON,DC 20052. RP Geller, NL (reprint author), NHLBI,OFF BIOSTAT RES,DIV EPIDEMIOL & CLIN APPLICAT,BLDG 10,BETHESDA,MD 20892, USA. NR 13 TC 0 Z9 0 U1 0 U2 1 PU INST MATHEMATICAL STATISTICS PI HAYWARD PA IMS BUSINESS OFFICE-SUITE 6 3401 INVESTMENT BLVD, HAYWARD, CA 94545 SN 0883-4237 J9 STAT SCI JI Stat. Sci. PD MAY PY 1997 VL 12 IS 2 BP 113 EP 118 PG 6 WC Statistics & Probability SC Mathematics GA XT268 UT WOS:A1997XT26800007 ER PT J AU Green, SB AF Green, SB TI A conversation with Fred Ederer SO STATISTICAL SCIENCE LA English DT Article ID TOPICS AB Fred Ederer was born on March 5, 1926, in Vienna, Austria. He received a B.S. degree in mathematics and science from the City College of New York, an M.A. degree in statistics from American University and did further graduate work in biostatistics at Columbia and Stanford Universities. He is a Fellow of the American Statistical Association, of the American College of Epidemiology and of the American Heart Association's Council on Epidemiology. He has been on the editorial boards of the American Journal of Ophthalmology, Survey of Ophthalmology and the American Journal of Epidemiology. He has served on the Council. on Epidemiology, the American Heart Association and the Regional Advisory Board of the Eastern North American Region of the Biometric Society, and he was on the Founding Board of Directors for both the Society for Clinical Trials and the American College of Epidemiology. His tenure at the National Institutes of Health (NIH) included the years 1957 through 1986. He began at the National Cancer Institute, moving next to the National Heart Institute and then spending the next half of his NIH career at the National Eye Institute (NEI). His first position at NEI was as Head of the Section on Clinical Trials, then Chief of the Office of Biometry and Epidemiology and, finally, Associate Director for Biometry and Epidemiology. He was awarded the Superior Service Award, one of the highest civilian awards given at NIH. Since leaving NIH, he has been Senior Epidemiologist at the EMMES Corporation and Adjunct Professor in the Division of Biostatistics at the University of Minnesota. RP Green, SB (reprint author), NCI,CLIN & DIAGNOST TRIALS SECT,BIOMETRY BRANCH,DIV CANC PREVENT & CONTROL,NIH,ROCKVILLE,MD 20892, USA. NR 27 TC 1 Z9 1 U1 1 U2 1 PU INST MATHEMATICAL STATISTICS PI HAYWARD PA IMS BUSINESS OFFICE-SUITE 6 3401 INVESTMENT BLVD, HAYWARD, CA 94545 SN 0883-4237 J9 STAT SCI JI Stat. Sci. PD MAY PY 1997 VL 12 IS 2 BP 125 EP 131 PG 7 WC Statistics & Probability SC Mathematics GA XT268 UT WOS:A1997XT26800009 ER PT J AU Howard, G Anderson, R Johnson, NJ Sorlie, P Russell, G Howard, VJ AF Howard, G Anderson, R Johnson, NJ Sorlie, P Russell, G Howard, VJ TI Evaluation of social status as a contributing factor to the stroke belt region of the United States SO STROKE LA English DT Article DE cause of death; cerebrovascular disorders; southeastern United States; models, statistical ID SOCIOECONOMIC-STATUS; GEOGRAPHIC-DISTRIBUTION; CARDIOVASCULAR-DISEASE; MORTALITY; DECLINE; AGE AB Background and Purpose The southeastern United States has stroke mortality rates above the national average. The causes for this excess mortality are unknown; however, lower socioeconomic status (SES) is a risk factor for stroke, and the lower SES in the Southeast is a potential cause. In this report we assess the proportion of the excess stroke mortality attributable to SES. Methods The more than 400 000 participants in the National Longitudinal Mortality Study were categorized into three regions: the coastal plain region of North Carolina, South Carolina, and Georgia (''stroke buckle''); the remainder of these states plus five other southern states (''stroke belt''); and the remainder of the United States. The stroke mortality rates were calculated with and without adjustment for SES, and the proportion of the excess mortality attributable to SES was estimated. Results In persons between the ages of 35 and 54 years, stroke mortality in the stroke buckle is estimated to be more than twice that of the rest of the nation and 1.7 times greater for ages 55 to 74 years. For persons in the stroke belt, the stroke mortality was 1.3 times greater than that in the rest of the nation for the ages of 35 to 54 and 55 to 74 years. Less than 16% of this excess stroke morality was attributable to SES. Conclusions SES does not appear to be a major contributor to the excess mortality in the southeastern United States. Of additional concern is the stroke buckle region, which was shown to have stroke mortality rates substantially greater than those in the traditionally recognized stroke belt. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT NEUROL,WINSTON SALEM,NC 27157. US BUR CENSUS,WASHINGTON,DC 20233. NHLBI,BETHESDA,MD 20892. RP Howard, G (reprint author), WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,MED CTR BLVD,WINSTON SALEM,NC 27157, USA. FU PHS HHS [R03-53339] NR 29 TC 58 Z9 58 U1 1 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 1997 VL 28 IS 5 BP 936 EP 940 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA WZ267 UT WOS:A1997WZ26700009 PM 9158628 ER PT J AU Wagenknecht, LE DAgostino, R Savage, PJ OLeary, DH Saad, MF Haffner, SM AF Wagenknecht, LE DAgostino, R Savage, PJ OLeary, DH Saad, MF Haffner, SM TI Duration of diabetes and carotid wall thickness - The Insulin Resistance Atherosclerosis Study (IRAS) SO STROKE LA English DT Article DE atherosclerosis; carotid arteries; diabetes mellitus; hyperglycemia ID CORONARY HEART-DISEASE; CARDIOVASCULAR RISK-FACTORS; GLYCOSYLATION END-PRODUCTS; B-MODE ULTRASOUND; ARTERIAL-WALL; MEDIAL THICKNESS; MELLITUS; COMPLICATIONS; ASSOCIATION; MORTALITY AB Background and Purpose Diabetes is a major risk factor for morbidity and mortality from cardiovascular disease. However, the role of the primary metabolic abnormality of diabetes (chronic hyperglycemia) in this disease process has not been fully elucidated. Methods A cross-sectional analysis was conducted among 489 persons with non-insulin-dependent diabetes mellitus; 299 were established diabetics (diagnosed previously) and 190 were newly diagnosed at the time of the Insulin Resistance Atherosclerosis Study (IRAS) examination. These men and women, of three different ethnic groups, were participants in IRAS. Established diabetes (versus newly diagnosed diabetes) and mean fasting glucose level were used as measures of hyperglycemic burden. Intimal-medial wall thickness (IMT) of the internal (ICA) and common (CCA) carotid arteries were used as indices of atherosclerosis. Results The mean duration of disease among established diabetics was 7 years. The mean CCA IMT and ICA IMT were 872 and 946 mu m, respectively. Established diabetes and mean fasting glucose level were positively associated with increased CCA IMT (P<.05) but not ICA IMT, even after adjustment for numerous cardiovascular disease risk factors. CCA IMT was increased by 70 mu m in established diabetics (versus newly diagnosed diabetics) and by 26 mu m per 1 SD of fasting glucose. Among established diabetics, however, duration of known diabetes (number of years) was not significantly related to IMT. Conclusions Among diabetics in IRAS, established diabetes and fasting glucose level were each independently associated with CCA IMT, suggesting that chronic hyperglycemia or its associated metabolic abnormalities may lead to increased risk of atherosclerosis. C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,NIH,BETHESDA,MD 20892. TUFTS UNIV NEW ENGLAND MED CTR,DEPT RADIOL,BOSTON,MA 02111. UNIV SO CALIF,MED CTR,DEPT MED,LOS ANGELES,CA. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. RP Wagenknecht, LE (reprint author), WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT MICROBIOL & PUBL HLTH,MED CTR BLVD,WINSTON SALEM,NC 27157, USA. RI Dagostino Jr, Ralph/C-4060-2017 OI Dagostino Jr, Ralph/0000-0002-3550-8395 FU NHLBI NIH HHS [U01-HL 47887, U01-HL 47889, U01-HL 47890] NR 46 TC 91 Z9 96 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 1997 VL 28 IS 5 BP 999 EP 1005 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA WZ267 UT WOS:A1997WZ26700022 PM 9158641 ER PT J AU Hershkovitz, MA Zimmer, EA AF Hershkovitz, MA Zimmer, EA TI On the evolutionary origins of the cacti SO TAXON LA English DT Article ID RIBOSOMAL DNA; PHYLOGENY; CLASSIFICATION; CENTROSPERMAE; PORTULACACEAE AB Understanding evolutionary responses of plants to desert environments depends upon phylogenetic knowledge of desert plants. The diverse American desert family Cactaceae has been presumed, on the basis of distinctiveness, to be phylogenetically isolated and relatively ancient (> 65 million years old). Using maximum likelihood and parsimony analyses of the rapidly evolving internal transcribed spacer (ITS) sequences of nuclear ribosomal DNA (nrDNA), we show that the cacti are phylogenetically nested among other aridity-adapted lineages of the angiosperm family Portulacaceae. The ITS divergence between pereskioid cacti and the genus Talinum (Portulacaceae) is less than that between many Portulacaceae genera. Synthesis of the ITS data with morphological and chloroplast DNA evidence suggests an origin of cacti in mid-Tertiary, c. 30 million years ago, and a later Tertiary diversification coincident with development of the American desert. This, in turn, implies that the diversification rate in cacti was much higher than in their nearest relatives. The present results illustrate the central role of phylogenetic reconstruction in ecological and evolutionary theory. C1 SMITHSONIAN INST,MUSEUM SUPPORT CTR,LAB MOL SYSTEMAT,WASHINGTON,DC 20560. RP Hershkovitz, MA (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT GENBANK,NIH,BLDG 38A,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. RI Zimmer, Elizabeth/G-3890-2011 NR 49 TC 80 Z9 87 U1 7 U2 22 PU INT ASSOC PLANT TAXONOMY PI BERLIN PA BOTANISCHER GARTEN BOTANISCHES MUSEUM BERLIN-DAHLEM, KONIGIN-LUISE-STRABE 6-8, D-14191 BERLIN, GERMANY SN 0040-0262 J9 TAXON JI Taxon PD MAY PY 1997 VL 46 IS 2 BP 217 EP 232 DI 10.2307/1224092 PG 16 WC Plant Sciences; Evolutionary Biology SC Plant Sciences; Evolutionary Biology GA XD259 UT WOS:A1997XD25900001 ER PT J AU Haseman, JK Young, E Eustis, SL Hailey, JR AF Haseman, JK Young, E Eustis, SL Hailey, JR TI Body weight-tumor incidence correlations in long-term rodent carcinogenicity studies SO TOXICOLOGIC PATHOLOGY LA English DT Article DE tumor associations; historical control data; Fischer-343 rats; B6C3Fl mice; pituitary gland tumors; interstitial cell testis tumors; logistic regression models; National Toxicology Program ID MICE; RATS; RESTRICTION; SURVIVAL AB Associations between body weight and turner incidence and among the incidences of selected site-specific tumors were examined for more than 4,000 male and female Fischer-344 rats and B6C3F1 mice in the National Toxicology Program historical control database. Incidences of certain site-specific tumors-, most notably mammary gland and pituitary gland tumors in rats and liver tumors in mice, were shown to have a strong positive correlation with 52-wk body weight. Using individual animal data, logistic regression models were derived for predicting site-specific tumor incidence as a function of 52-wk body weight, age, and other factors. This association between body weight and tumor incidence can explain many of the decreased tumor incidences observed in National Toxicology Program carcinogenicity studies. Body weight differences between dosed and control groups can also mask carcinogenic effects for those sites sensitive to body weight changes. Thus, when designing long-term rodent carcinogenicity studies, measures should be taken to minimize potential body weight differences between dosed and control groups. There were a number of small but significant negative correlations among tumor incidences, reflecting primarily the lethality of the tumors in question. None of these correlations (nor the 2, small positive correlations found) are likely to have any impact on the interpretation of experimental results. However, the high negative correlation between pituitary gland and testis tumors in male Fischer-344 rats cannot be dismissed so easily, does not reflect tumor lethality, and is currently being studied further. RP Haseman, JK (reprint author), NIEHS,STAT & BIOMATH BRANCH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 27 TC 65 Z9 65 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD MAY-JUN PY 1997 VL 25 IS 3 BP 256 EP 263 PG 8 WC Pathology; Toxicology SC Pathology; Toxicology GA XH035 UT WOS:A1997XH03500002 PM 9210256 ER PT J AU Thompson, MB AF Thompson, MB TI The Min mouse: A genetic model for intestinal carcinogenesis SO TOXICOLOGIC PATHOLOGY LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; APC GENE; MAJOR MODIFIER; MOM1 LOCUS; NEOPLASIA; MUTATION; CANDIDATE; HOMOLOG; TUMORS; CANCER RP Thompson, MB (reprint author), NIEHS,MAIL DROP C2-08,RES TRIANGLE PK,NC 27709, USA. NR 31 TC 7 Z9 7 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD MAY-JUN PY 1997 VL 25 IS 3 BP 329 EP 332 PG 4 WC Pathology; Toxicology SC Pathology; Toxicology GA XH035 UT WOS:A1997XH03500012 PM 9210266 ER PT J AU Li, LH Wine, RN Miller, DS Reece, JM Smith, M Chapin, RE AF Li, LH Wine, RN Miller, DS Reece, JM Smith, M Chapin, RE TI Protection against methoxyacetic-acid-induced spermatocyte apoptosis with calcium channel blockers in cultured rat seminiferous tubules: Possible mechanisms SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID GLYCOL MONOMETHYL ETHER; FREE CYTOSOLIC CALCIUM; SKELETAL-MUSCLE; CYCLOSPORINE-A; GUINEA-PIG; TESTICULAR TOXICITY; 2-METHOXYETHANOL ME; PHORBOL ESTER; CELL INJURY; CA2+ AB A calcium-mediated mechanism underlying spermatocyte apoptosis induced by 2-methoxyethanol (2-ME) has been previously proposed, This hypothesis was tested in vitro in the present study using cultured juvenile (25 days old) and adult rat seminiferous tubules (JRST and ARST, respectively) with methoxyacetic acid (MAA, the active metabolite of 2-ME). In JRST, spermatocyte degeneration was morphologically obvious 19 hr after a 5-hr exposure to 5 mM MAA. The lesion was unaffected by the presence or absence of extratubular Ca2+, However, MAA-induced cell death was significantly prevented by cotreatment with the dihydropyridines (DHP) nifedipine (50 mu M) and nicardipine (20 mu M), as well as verapamil (50 mu M) and TMB-8 (50 mu M), all of which are able to inhibit calcium movement through plasma membranes, However, neither ryanodine, dantrolene, nor cyclosporin A and ruthenium red, which inhibit Ca2+ mobilization from intracellular stores (endoplasmic reticulum and mitochondria), affected the MAA-induced cell death, Inhibition of calcium mobilization through IP3-sensitive pathways by blocking the product of IP3 with manoalide, neomycin, and U73122 did not block the MAA-induced lesion. The protective effects of 50 mu M nifedipine and 50 mu M TMB-8 were also observed in ARSTs treated with 10 mM MAA for 5 hr. However, when rat testicular sections were immunohistochemically stained with monoclonal antibodies specific for the a, (the DHP receptor) or the alpha(2) subunits of DHP-sensitive calcium channels, no positive staining was found. Finally, in an attempt to see whether the intracellular free calcium concentrations ([Ca2+](i)) in germ cells were increased after the MAA treatment, intact seminiferous tubules were loaded with indo-1 and were measured using laser-scanning confocal microscopy. No detectable increase in the signal in MAA-sensitive spermatocytes was observed, while a 34-54% increase in the signal could be detected in the same cell types when tubules were exposed to 10 mu M of the calcium ionophore 4-bromo-A23187 for 5 min, Collectively, these data suggest that the protective effect of calcium channel blockers against the MAA-induced spermatocyte apoptosis is probably not through their blocking effect on DHP-sensitive calcium channels, We postulate alternate mechanisms based on stabilization of cells membranes, or interactions with calmodulin or protein kinase C. (C) 1997 Academic Press. C1 NIEHS, NATL TOXICOL PROGRAM, REPROD TOXICOL GRP, RES TRIANGLE PK, NC 27709 USA. NIEHS, CELLULAR & MOL PHARMACOL LAB, RES TRIANGLE PK, NC 27709 USA. ANALYT SCI INC, DURHAM, NC 27713 USA. OI Chapin, Robert/0000-0002-5997-1261 NR 73 TC 29 Z9 29 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAY PY 1997 VL 144 IS 1 BP 105 EP 119 DI 10.1006/taap.1997.8129 PG 15 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA WX674 UT WOS:A1997WX67400012 PM 9169075 ER PT J AU Daly, JW Padgett, WL Saunders, RL Cover, JF AF Daly, JW Padgett, WL Saunders, RL Cover, JF TI Absence of tetrodotoxins in a captive-raised riparian frog, Atelopus varius SO TOXICON LA English DT Article ID COSTA RICAN FROG; TARICHA-GRANULOSA; SKIN; CHIRIQUIENSIS; OXYRHYNCHUS; BUFONIDAE; BINDING; FAMILY; SITE AB Bufonid frogs of the genus Atelopus contain two classes of skin toxins, namely the steroidal bufadienolides and the water-soluble tetrodotoxins. Frogs of the Panamanian species Atelopus varius have now been raised in captivity and levels in skin extracts of bufadienolides and of tetrodotoxin-like compounds assessed, using inhibition of [H-3]ouabain binding and inhibition of [H-3]saxitoxin binding, respectively. Levels of ouabain equivalents, corresponding to bufadienolides, were comparable to those found in wild-caught frogs from the same population in Panama, while tetrodotoxin-like activity was undetectable. The results strongly implicate environmental factors, perhaps symbiotic microorganisms, in the genesis of tetrodotoxins in the skin of frogs of the genus Atelopus, while indicating that the frog itself produces the skin bufadienolides. (C) 1997 Elsevier Science Ltd. C1 CINCINNATI ZOO & BOT GARDEN,CINCINNATI,OH 45111. NATL AQUARIUM,BALTIMORE,MD 21202. RP Daly, JW (reprint author), NIH,BIOORGAN CHEM LAB,BETHESDA,MD 20892, USA. NR 20 TC 29 Z9 31 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0041-0101 J9 TOXICON JI Toxicon PD MAY PY 1997 VL 35 IS 5 BP 705 EP 709 DI 10.1016/S0041-0101(96)00165-1 PG 5 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA XE623 UT WOS:A1997XE62300009 PM 9203295 ER PT J AU Cooper, PJ Guderian, RH Nutman, TB Taylor, DW AF Cooper, PJ Guderian, RH Nutman, TB Taylor, DW TI Human infection with Onchocerca volvulus does not affect the T helper cell phenotype of the cellular immune response to mycobacterial antigen SO TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE LA English DT Article DE onchocerciasis; Onchocerca volvulus; cellular immunity; interferon gamma; interleukin 5 ID VACCINATIONS; BCG AB In order to determine whether infection with Onchocerca volvulus might modify the immune response to mycobacterial antigen, the proliferative and cytokine responses of peripheral blood mononuclear cells from 117 persons infected with O. volvulus and 36 non-endemic control subjects were compared. Tuberculin-stimulated cellular proliferative responses and production of T-h1-type cytokines (interferon gamma) were reduced in persons infected with O. volvulus compared to controls, However, there was no evidence of polarization of the immune response towards a T-h2-type phenotype (interleukin 5) in infected individuals compared to controls. C1 HOSP VOZANDES,ONCHOCERIASIS CONTROL PROGRAMME,QUITO,ECUADOR. UNIV CAMBRIDGE,DEPT PATHOL,CAMBRIDGE CB2 1QP,ENGLAND. RP Cooper, PJ (reprint author), NATL INST HLTH,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 19 TC 8 Z9 8 U1 1 U2 2 PU ROYAL SOC TROPICAL MEDICINE PI LONDON PA MANSON HOUSE 26 PORTLAND PLACE, LONDON, ENGLAND W1N 4EY SN 0035-9203 J9 T ROY SOC TROP MED H JI Trans. Roy. Soc. Trop. Med. Hyg. PD MAY-JUN PY 1997 VL 91 IS 3 BP 350 EP 352 DI 10.1016/S0035-9203(97)90103-6 PG 3 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA XE698 UT WOS:A1997XE69800031 PM 9231215 ER PT J AU Schuck, P Minton, AP AF Schuck, P Minton, AP TI Kinetic data reliability - Reply SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Letter RP Schuck, P (reprint author), NIDDK,BIOCHEM PHARMACOL LAB,NATL INST HLTH,BETHESDA,MD 20892, USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD MAY PY 1997 VL 22 IS 5 BP 149 EP 149 DI 10.1016/S0968-0004(97)01038-4 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WZ504 UT WOS:A1997WZ50400003 ER PT J AU Schuck, P Minton, AP AF Schuck, P Minton, AP TI Self-consistency of kinetic data - Reply SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Letter RP Schuck, P (reprint author), NIDDK,BIOCHEM PHARMACOL LAB,NATL INST HLTH,BETHESDA,MD 20892, USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD MAY PY 1997 VL 22 IS 5 BP 150 EP 150 DI 10.1016/S0968-0004(97)01040-2 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WZ504 UT WOS:A1997WZ50400005 ER PT J AU Neuwald, AF Landsman, D AF Neuwald, AF Landsman, D TI GCN5-related histone N-acetyltransferases belong to a diverse superfamily that includes the yeast SPT10 protein SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID SACCHAROMYCES-CEREVISIAE; SPT21 GENES RP Neuwald, AF (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,NATL INST HLTH,BETHESDA,MD 20894, USA. RI Landsman, David/C-5923-2009; OI Landsman, David/0000-0002-9819-6675 NR 22 TC 321 Z9 329 U1 1 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD MAY PY 1997 VL 22 IS 5 BP 154 EP 155 DI 10.1016/S0968-0004(97)01034-7 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WZ504 UT WOS:A1997WZ50400007 PM 9175471 ER PT J AU Hengen, PN AF Hengen, PN TI Methods and reagents - Protecting vector DNA from UV light SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review AB Methods and reagents is a unique monthly column that highlights current discussions in the newsgroup bionet.molbio.methds-reagnts, available on the Internet. This month's column discusses how to squeeze more life out of DNA isolated from agarose gels. For details on how to partake in the newsgroup, see the accompanying box. RP Hengen, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD MAY PY 1997 VL 22 IS 5 BP 182 EP 183 DI 10.1016/S0968-0004(97)01046-3 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WZ504 UT WOS:A1997WZ50400014 PM 9175478 ER PT J AU Vondrasek, J Wlodawer, A AF Vondrasek, J Wlodawer, A TI Database of HIV proteinase structures SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID IMMUNODEFICIENCY-VIRUS PROTEASE; INHIBITOR RP Vondrasek, J (reprint author), NCI,FREDERICK CANC RES & DEV CTR,MACROMOL STRUCT LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702, USA. RI Vondrasek, JIri/A-4244-2008 NR 5 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD MAY PY 1997 VL 22 IS 5 BP 183 EP 183 DI 10.1016/S0968-0004(97)01024-4 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WZ504 UT WOS:A1997WZ50400015 PM 9175479 ER PT J AU Loh, YP Snell, CR Cool, DR AF Loh, YP Snell, CR Cool, DR TI Receptor-mediated targeting of hormones to secretory granules - Role of carboxypeptidase E SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID TRANS-GOLGI NETWORK; ENZYME-ACTIVITY; SORTING SIGNAL; PATHWAY; PROOPIOMELANOCORTIN; PROTEINS; CELLS; IDENTIFICATION; CLEAVAGE; VESICLES AB Peptide hormones, neuropeptides, and other molecules such as the granins are specifically packaged into granules of the regulated secretory pathway and released in a calcium-dependent manner upon stimulation. Many of these molecules are synthesized as larger precursors (prohormones) that are processed to biologically active products within the granules. It has now became apparent that prohormones, proneuropeptides, and the granins contain conformation-dependent sorting signal motifs that facilitate their specific sorting and packaging into regulated secretory granules. Recently, a receptor to which these sorting signals bind has been identified as the membrane form of carboxypeptidase E (CPE) and localized to the Golgi apparatus, where sorting occurs, specifically at the trans-Golgi network. In this article, we review the evidence for a sorting signal-receptor-mediated mechanism for routing peptide hormones and prohormones to the regulated secretory granules. We also describe a mouse model, Cpe(fat), which has the CPE gene naturally mutated. Pituitary hormones were misrouted and secreted in an unregulated manner via the constitutive pathway in these Cpe(fat) mice, leading to endocrine disorders. (C) 1997, Elsevier Science Inc. C1 NOVARTIS INST MED RES,LONDON WC1E 6BN,ENGLAND. RP Loh, YP (reprint author), NICHHD,CELLULAR NEUROBIOL SECT,DEV NEUROBIOL LAB,NIH,BETHESDA,MD 20892, USA. NR 37 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD MAY-JUN PY 1997 VL 8 IS 4 BP 130 EP 137 DI 10.1016/S1043-2760(97)00010-6 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG345 UT WOS:A1997XG34500002 PM 18406798 ER PT J AU Lindzey, J Korach, KS AF Lindzey, J Korach, KS TI Developmental and physiological effects of estrogen receptor gene disruption in mice SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID PROGESTERONE-RECEPTOR; LUTEINIZING-HORMONE; MESSENGER-RNA; LEYDIG-CELLS; GROWTH; MOUSE; EXPRESSION; DIFFERENTIATION; STIMULATION; INFERTILITY AB Disruption of the estrogen receptor (ER) gene in mice causes infertility in both sexes. Infertility in female ER knockout (ERKO) mice results from altered development of accessory sex structures, disrupted endocrine physiology, and disrupted gametogenesis. Male accessory sex structures appear relatively normal, with infertility stemming from altered sexual behaviors and disrupted gametogenesis. These findings provide significant insights into the biological importance of the ER and suggest further nl eas for examining the impact of estrogens on reproductive biology. (C) 1997, Elsevier Science Inc. RP Lindzey, J (reprint author), NIEHS,REPROD & DEV TOXICOL LAB,RECEPTOR BIOL SECT,NIH,RES TRIANGLE PK,NC 27709, USA. OI Korach, Kenneth/0000-0002-7765-418X NR 46 TC 33 Z9 33 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD MAY-JUN PY 1997 VL 8 IS 4 BP 137 EP 145 DI 10.1016/S1043-2760(97)00007-6 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA XG345 UT WOS:A1997XG34500003 PM 18406799 ER PT J AU Garfinkel, DJ AF Garfinkel, DJ TI Genetic loose change: How retroelements and reverse transcriptase heal broken chromosomes SO TRENDS IN MICROBIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; HOMOLOGOUS RECOMBINATION; CDNA RP Garfinkel, DJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,GENE REGULAT & CHROMOSOME BIOL LAB,POB B,FREDERICK,MD 21702, USA. NR 14 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD MAY PY 1997 VL 5 IS 5 BP 173 EP 175 DI 10.1016/S0966-842X(97)01018-4 PG 3 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA WY695 UT WOS:A1997WY69500004 PM 9160501 ER PT J AU Covacci, A Falkow, S Berg, DE Rappuoli, R AF Covacci, A Falkow, S Berg, DE Rappuoli, R TI Did the inheritance of a pathogenicity island modify the virulence of Helicobacter pylori? SO TRENDS IN MICROBIOLOGY LA English DT Article ID VACUOLATING CYTOTOXIN; SECRETION; DISEASE; STRAINS; CAGA AB Strains of Helicobacter pylori from patients with peptic ulcer disease and gastric cancer contain a 40-kb fragment of DNA that is not present in isolates from carriers with asymptomatic infections. The discovery of the cag pathogenicity island suggests that virulence has evolved by quantum leaps through the inheritance of one or more DNA insertions. C1 STANFORD UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. NIAID,ROCKY MT LAB,NIH,HAMILTON,MT 59840. WASHINGTON UNIV,SCH MED,DEPT MICROBIOL & MOL GENET,ST LOUIS,MO 63110. RP Covacci, A (reprint author), CHIRON VACCINES,IRIS,DEPT BIOL MOL,VIA FIORENTINA 1,I-53100 SIENA,ITALY. NR 25 TC 121 Z9 127 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD MAY PY 1997 VL 5 IS 5 BP 205 EP 208 DI 10.1016/S0966-842X(97)01035-4 PG 4 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA WY695 UT WOS:A1997WY69500015 PM 9160510 ER PT J AU Jones, CA Nyberg, L AF Jones, CA Nyberg, L TI Epidemiology of interstitial cystitis SO UROLOGY LA English DT Article ID AUTOIMMUNE-DISEASE; DIAGNOSIS; PROTEIN; URINE AB Objectives. To discuss what is currently known about the population prevalence of interstitial cystitis (IC) and demographic characteristics of IC patients. Methods. Changes over time in the criteria for diagnosis of IC are described. The 3 published studies of the population prevalence of IC are reviewed. Epidemiologic issues important in the design of studies of IC are cited. Results. IC is a disease of chronic voiding symptoms. There is very little reliable information published on the etiology, risk factors, or number of persons affected. The criteria used for diagnosis of IC by different investigators have been variable. In 1988, research criteria for a case definition of IC were published, to be applied for IC patients enrolled in National Institutes of Health-funded studies. Three published studies of the population prevalence of IC are available. Each study used different criteria for defining a case of IC, and none used the NIH research criteria to define a case. Prevalence estimates for IC vary significantly, from 10 cases/100,000 reported in Finland in 1975, (based on hospital record review), to 30/100,000 in the United States in 1987, (based on a mailed survey of board certified urologists), to 510 cases/100,000 in the United States in 1989, (based on participant self-report in the 1989 National Health Interview Survey). It is unclear the extent to which these estimates represent true differences in prevalence, rather than reflect the different methods used to define an IC case. Several investigators have reported demographic characteristics of the IC patients followed in their clinics. All studies of adults show a marked female predominance, with reported onset of symptoms generally in the middle years of life. Patients may experience a delay of years from the onset of symptoms to the time of definitive diagnosis. The natural history of symptoms of IC has been reported to be that of a subacute onset with a rapid peak in severity, and then a relatively constant plateau of chronic symptoms thereafter. However, many patients do experience remissions and flares in their disease symptoms. Conclusions. Few therapies for IC have been evaluated using rigorous epidemiologic methods. Many questions remain to be answered. New studies of IC should include epidemiologic consultation at the stage of study design. (C) 1997 by Elsevier Science Inc. RP Jones, CA (reprint author), NIDDK,NIH,NATCHER BLDG,RM 6AS13K,45 CTR DR,MSC 6600,BETHESDA,MD 20892, USA. NR 44 TC 109 Z9 116 U1 0 U2 3 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD MAY PY 1997 VL 49 IS 5A SU S BP 2 EP 9 DI 10.1016/S0090-4295(99)80327-6 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA WX423 UT WOS:A1997WX42300002 PM 9145997 ER PT J AU Simon, LJ Landis, JR Erickson, DR Nyberg, LM Wein, AJ Foy, M Hanno, PM Monson, F Nigro, D Whitmore, KE Cook, YLM Erickson, D Gray, DW Kunselman, AR Phillips, B Boehmer, SJ Paynter, A Abele, ST Rawa, P Phillips, E Beers, B Hilderbrand, R Durborow, S Parsons, CL Stein, P Williams, M Culkin, DJ Roy, JB Hurst, RE Mulrooney, L Walker, L Scaheffer, A Neiweglowski, M Maurer, G Tomaszewski, JE Wang, LP Uehling, DT Messing, EM Pauk, D Williams, T Russack, V Diokno, AC Afanasyev, A Anton, E Steinert, BW Kusek, JW Jones, C Kirkemo, A Burks, D Peabody, M OLeary, M AF Simon, LJ Landis, JR Erickson, DR Nyberg, LM Wein, AJ Foy, M Hanno, PM Monson, F Nigro, D Whitmore, KE Cook, YLM Erickson, D Gray, DW Kunselman, AR Phillips, B Boehmer, SJ Paynter, A Abele, ST Rawa, P Phillips, E Beers, B Hilderbrand, R Durborow, S Parsons, CL Stein, P Williams, M Culkin, DJ Roy, JB Hurst, RE Mulrooney, L Walker, L Scaheffer, A Neiweglowski, M Maurer, G Tomaszewski, JE Wang, LP Uehling, DT Messing, EM Pauk, D Williams, T Russack, V Diokno, AC Afanasyev, A Anton, E Steinert, BW Kusek, JW Jones, C Kirkemo, A Burks, D Peabody, M OLeary, M TI The interstitial cystitis data base study: Concepts and preliminary baseline descriptive statistics SO UROLOGY LA English DT Article AB Objectives. To describe the design, patient population, and data and specimen collection aspects of the Interstitial Cystitis Data Base (ICDB) Study and to provide preliminary descriptive statistics and inferential results from an interim analysis. Methods. All 424 study participants successfully enrolled in the ICDB Study prior to December 31, 1995, were selected for an interim analysis and were classified into 1 of 3 symptom severity subgroups. Statistical tests for associations among these symptom severity subgroups and a broad range of baseline characteristics were conducted using Mantel-Haenszel procedures to adjust for variation among clinical centers. Results. ICDB Study patients are predominantly female (91.5%), white (91.0%), with an average age at enrollment of 44.3 years. Nearly 45% of these patients underwent a cystoscopy at baseline screening, among whom there was an overall prevalence of 10.5% for Hunner's patch and 90% for glomerulations. Urodynamic evaluation for the entire 424 patients demonstrated that volumes at first sensation and at maximal capacity were inversely associated with symptom severity subgroups. A broad range of symptoms were analyzed, indicating that nearly 40% of patients reported urinating 15 times or more during awake hours, and more than 20% reported voiding at least 4 times per night. Almost half (47.9%) reported constant urgency and 23.6% reported having severe pain. Patients in the severe symptom subgroup reported greater limitations in selected quality-of-life indicators than those with less severe symptoms. Conclusions. This interim analysis of the ICDB Study data was compared to previous epidemiologic studies of IC and provides an essential foundation for further analytic investigations of baseline associations and longitudinal trends. (C) 1997 by Elsevier Science Inc. C1 PENN STATE UNIV,COLL MED,CTR BIOSTAT & EPIDEMIOL,HERSHEY,PA 17033. PENN STATE UNIV,COLL MED,DEPT UROL,HERSHEY,PA 17033. NIDDKD,BETHESDA,MD 20892. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. UNIV OKLAHOMA,NORMAN,OK 73019. NORTHWESTERN UNIV,EVANSTON,IL 60208. UNIV WISCONSIN,MADISON,WI 53706. WILLIAM BEAUMONT HOSP,ROYAL OAK,MI. HENRY FORD HOSP,DETROIT,MI. PENN STATE UNIV,COLL MED,DATA COORDINATING CTR,HERSHEY,PA 17033. UNIV PENN,ANAT PATHOL LAB,PHILADELPHIA,PA 19104. UNIV NEW MEXICO,ALBUQUERQUE,NM 87131. SCRIPPS CLIN,LA JOLLA,CA. UNIV ROCHESTER,ROCHESTER,NY 14627. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. UNIV PENN,PATHOL READING GRP,PHILADELPHIA,PA 19104. RI Landis, J. Richard/A-9330-2010 NR 24 TC 150 Z9 153 U1 1 U2 3 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD MAY PY 1997 VL 49 IS 5A SU S BP 64 EP 75 DI 10.1016/S0090-4295(99)80334-3 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA WX423 UT WOS:A1997WX42300009 PM 9146004 ER PT J AU Kirkemo, A Peabody, M Diokno, AC Afanasyev, A Nyberg, LM Landis, JR Cook, YLM Simon, LJ AF Kirkemo, A Peabody, M Diokno, AC Afanasyev, A Nyberg, LM Landis, JR Cook, YLM Simon, LJ TI Associations among urodynamic findings and symptoms in women enrolled in the interstitial cystitis data base (ICDB) study SO UROLOGY LA English DT Article AB Objectives. The goal of this study was to correlate the cystometric findings with the presenting symptoms of the 388 women enrolled in the NIH/NIDDK-funded Interstitial Cystitis Data Base (ICDB) Study as of December 31, 1995. Methods. All patients underwent a complete history and physical and completed standardized questionnaires to assess voiding symptoms and quality of life (QOL). A 3-day voiding log was also obtained, followed by a baseline urodynamic exam. All results are expressed as mean values tl standard deviation, and all reported correlations were significant. Results. A correlation was seen between reported daytime, nighttime, and 24-hour frequency, and both volume at first sensation to void (VFSV) and maximal cystometric capacity (VMCC). Patients with constant severe urgency had smaller VFSV, 63 +/- 59 mL versus 108 +/- 90 mL, and lower VMCC, 163 +/- 102 mL versus 288 +/- 135 mL, than patients without the complaint. A negative trend was seen for both VFSV and VMCC versus the global symptom severity. An inverse trend was seen between minimal and maximal pain scores over the 4 weeks before the exam and VMCC. (No correlation existed between current pain noted during baseline screening visits and VFSV or VMCC.) No urodynamics correlates were seen with global measures of body pain and global health. Uninhibited detrusor contractions (UDCs) were seen in 56 of 384 patients (14.6%). A positive correlation was seen between urgency symptoms and the presence of UDCs. Correlations between the VFSV and the VMCC were made with both the average voided volume (AW) and the average maximal voided volume (AMW) as determined by a 3-day voiding log. Significant positive correlations were seen with each pair-wise comparison (P=0.001). Conclusion. These findings confirm that subjective measurements of symptoms associated with interstitial cystitis can be confirmed objectively with urodynamic studies. (C) 1997 by Elsevier, Science Inc. C1 PENN STATE UNIV,COLL MED,CTR BIOSTAT & EPIDEMIOL,HERSHEY,PA 17033. HENRY FORD HOSP,DEPT UROL,DETROIT,MI 48202. WILLIAM BEAUMONT HOSP,DEPT UROL,DETROIT,MI. NIDDKD,BETHESDA,MD 20892. RI Landis, J. Richard/A-9330-2010 FU NIDDK NIH HHS [UO1 DK45021] NR 13 TC 41 Z9 41 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD MAY PY 1997 VL 49 IS 5A SU S BP 76 EP 80 DI 10.1016/S0090-4295(99)80335-5 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA WX423 UT WOS:A1997WX42300010 PM 9146005 ER PT J AU Messing, E Pauk, D Schaeffer, A Nieweglowski, M Nyberg, LM Landis, JR Cook, YLM Simon, LJ AF Messing, E Pauk, D Schaeffer, A Nieweglowski, M Nyberg, LM Landis, JR Cook, YLM Simon, LJ TI Associations among cystoscopic findings and symptoms and physical examination findings in women enrolled in the interstitial cystitis data base (ICDB) study SO UROLOGY LA English DT Article AB Objectives. To determine if specific symptoms or physical findings were associated with findings on cystoscopic examination under anesthesia in patients participating in the Interstitial Cystitis Data Base (ICDB) Study. Methods. Subjects entering the ICDB Study completed symptom questionnaires and underwent physical examinations. Additionally, at the discretion of study investigators, 150 women underwent cystoscopy under anesthesia following a specific protocol of bladder distension at 70 to 80 cm irrigating fluid height and reinspection after capacity was reached and the irrigant drained. Results. Statistically significant (p <0.01) associations between bodily pain and urinary urgency with the presence of a Hunner's patch, and urinary frequency and urgency with a reduced bladder capacity under anesthesia were seen. Neither the findings of bloody irrigating fluid nor glomerulations were strongly associated with any symptom, and except for an association of urethral tenderness with Hunner's patch, no physical examination finding was associated with any cystoscopic findings. Conclusions. The strong associations of Hunner's patch and reduced bladder capacity under anesthesia with severe pain and urinary urgency, and urgency and frequency, respectively, indicate not only the importance of these findings in diagnosing interstitial cystitis, but also their potential utility in subclassifying this disease. (C) 1997 by Elsevier Science Inc. C1 PENN STATE UNIV,COLL MED,CTR BIOSTAT & EPIDEMIOL,HERSHEY,PA 17033. UNIV ROCHESTER,DEPT UROL,ROCHESTER,NY. UNIV WISCONSIN,DEPT UROL,MADISON,WI 53706. NORTHWESTERN UNIV,DEPT UROL,CHICAGO,IL 60611. NIDDKD,BETHESDA,MD 20892. RI Landis, J. Richard/A-9330-2010 FU NIDDK NIH HHS [U01 DK45021] NR 11 TC 52 Z9 53 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD MAY PY 1997 VL 49 IS 5A SU S BP 81 EP 85 DI 10.1016/S0090-4295(99)80336-7 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA WX423 UT WOS:A1997WX42300011 PM 9146006 ER PT J AU Nigro, DA Wein, AJ Foy, M Parsons, CL Williams, M Nyberg, LM Landis, JR Cook, YLM Simon, LJ AF Nigro, DA Wein, AJ Foy, M Parsons, CL Williams, M Nyberg, LM Landis, JR Cook, YLM Simon, LJ TI Associations among cystoscopic and urodynamic findings for women enrolled in the interstitial cystitis data base (ICDB) study SO UROLOGY LA English DT Article AB Objectives. Interstitial cystitis is a symptom complex characterized by pelvic pain, urinary urgency, urinary frequency, and nocturia. Patients with these symptoms, at the 5 clinical centers participating in the National Interstitial Cystitis Data Base (ICDB) Study, have been evaluated with history and physical exams, questionnaires, and urodynamic studies. Methods. Of the 388 female subjects entered in the study as of December 31, 1995, 150 women have undergone cystoscopy with hydrodistension. The data from the endoscopic procedures and the urodynamic studies were analyzed. The associations among cystoscopic and urodynamic findings were reviewed. Results. Patient demographics of this subgroup show a predominance of Caucasians 139/150 (92.7%), with the average age being 43 (+/-13.2) years. Of the total, 17 patients (11.3%) had a Hunner's patch (HP). The prevalence by center varied from a low of 2/38 (5.3%) to a high of 3/9 (33.3%). Bloody effluent following hydrodistension was present in 113/150 (75.3%). Glomerulations appeared in varying degrees (mild, moderate, severe) in 91.3% of the 150 patients. There was a strong inverse relationship (P <0.001) between bladder capacity under anesthesia and the presence of a HP (mean of 845 cc with HP absent versus a mean of 531 cc when present). The incidence of HP varied from 67.6% among women with a bladder capacity at hydrodistension of <400 cc to 3.8% for those with a bladder capacity of at least 800 cc. The presence and increasing severity of glomerulations was positively associated (P <0.003) with the presence of HP, ranging from 0/13 (0%) when glomerulations were not present to 6/31 (19.4%) when glomerulations were graded as severe. Of the patients with HP, 17/17 (100%) had glomerulations after hydrodistension. HP is more closely associated with the moderate to severe range of glomerulations (P <0.01). Nearly half of the patients with HP or 8/17 (47.1%) had ''moderate'' glomerulations, while 6/17 (35.3%) had ''severe'' glomerulations. The volume at first sensation to void on urodynamics (mean 87 cc without HP versus 34.7 cc with HP) was highly inversely associated (P=0.002) with the presence of HP, but not with any of the other cystoscopic findings. Of patients with HP, 94% had a volume at first sensation to void of less than or equal to 50 cc where only 36% of patients without HP had a volume at first sensation to void of less than or equal to 50 cc. The volume at maximum capacity on urodynamics was positively associated with the volume at hydrodistension (P <0.001). Conclusions. Overall, patients with HP had lower bladder capacities, lower volumes at first sensation to void, and more severe glomerulations. Thus, the presence of HP would imply a more severe case of interstitial cystitis. Logically, a higher bladder capacity on cystometrogram is associated with a higher volume at the time of hydrodistension, and bloody effluent is associated with more severe glomerulations. (C) 1997 by Elsevier Science Inc. C1 PENN STATE UNIV,COLL MED,CTR BIOSTAT & EPIDEMIOL,HERSHEY,PA 17033. UNIV PENN,DEPT UROL,PHILADELPHIA,PA 19104. UNIV CALIF SAN DIEGO,DEPT UROL,SAN DIEGO,CA 92103. NIDDKD,BETHESDA,MD 20892. RI Landis, J. Richard/A-9330-2010 FU NIDDK NIH HHS [UO1 DK45021] NR 7 TC 45 Z9 45 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD MAY PY 1997 VL 49 IS 5A SU S BP 86 EP 92 DI 10.1016/S0090-4295(99)80337-9 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA WX423 UT WOS:A1997WX42300012 PM 9146007 ER PT J AU Vargas, HI Kavoussi, LR Bartlett, DL Wagner, JR Venzon, DJ Fraker, DL Alexander, HR Linehan, WM Walther, MM AF Vargas, HI Kavoussi, LR Bartlett, DL Wagner, JR Venzon, DJ Fraker, DL Alexander, HR Linehan, WM Walther, MM TI Laparoscopic adrenalectomy: A new standard of care SO UROLOGY LA English DT Article ID POSTERIOR APPROACH; EXPERIENCE; PHEOCHROMOCYTOMA AB Objectives. Adrenalectomy is the mainstay of treatment for adrenal tumors. A variety of surgical approaches to the adrenal gland have been described. We studied the feasibility of laparoscopic adrenalectomy (LA), compared laparoscopic with open adrenalectomy (OA), and studied the hemodynamic changes in patients with pheochromocytoma. Methods. Our early experience with 20 consecutive LAs is compared with a contemporaneous, matched control cohort of 20 patients who underwent OA via a flank or subcostal incision. LA was performed via a transperitoneal approach, following a standardized surgical technique. Results. LA was successfully completed in 18 of 20 cases. Average operating time in the first 5 cases was 261 minutes, but, with further experience, a significant decrease in operative time was seen in the last cohort of 4 patients (155 minutes) (P = 0.0018). There was no significant difference in operative time or degree of blood loss between LA and OA groups. Patients who underwent LA required lower doses of postoperative parenteral narcotics (P = 0.0169), had a shorter hospital stay (mean 3.2 days) (P < 0.0001), and had a shorter convalescent period (mean 3.1 weeks) (P < 0.0001). Complications in the laparoscopic group (chronic port site pain in 1 patient, intra-abdominal fluid collection in another) occurred in the 2 patients who required open conversion. These 2 patients had large adrenal tumors (9 and 7 cm in diameter, respectively). LA resulted in similar hemodynamic changes as OA in patients with pheochromocytoma. Conclusions. LA is a safe and effective approach in most patients with adrenal pathology. Benefits include excellent operative exposure and visualization, less postoperative pain, shorter hospital stay and convalescent period, and improved cosmetic result. Pheochromocytoma is not a contraindication to LA. Patients with large adrenal tumors (larger than 6 cm), evidence of venous involvement, or invasion into surrounding tissue should be approached cautiously. C1 NCI,SECT UROL ONCOL,SURG BRANCH,NIH,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,BIOSTAT SECT,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,DATA MANAGEMENT SECT,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,DEPT UROL,BALTIMORE,MD. RI Venzon, David/B-3078-2008 NR 24 TC 94 Z9 96 U1 0 U2 1 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD MAY PY 1997 VL 49 IS 5 BP 673 EP 678 DI 10.1016/S0090-4295(97)00083-6 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA WW845 UT WOS:A1997WW84500004 PM 9145969 ER PT J AU McNeilly, PJ Torchin, CD Anderson, LW Kapetanovic, IM Kupferberg, HJ Strong, JM AF McNeilly, PJ Torchin, CD Anderson, LW Kapetanovic, IM Kupferberg, HJ Strong, JM TI In vitro glucuronidation of D-23129, a new anticonvulsant, by human liver microsomes and liver slices SO XENOBIOTICA LA English DT Article ID N-GLUCURONIDATION; UDP-GLUCURONOSYLTRANSFERASES; ANALGESIC FLUPIRTINE; HEPATIC MICROSOMES; RAT; METABOLISM; BIOTRANSFORMATION; PHARMACOKINETICS; TETRAZOLE; DRUG AB 1. The metabolic profile of D-23129, a new anticonvulsant agent, was studied in vitro using human liver microsomes and fresh liver slices. 2. Oxidative metabolism appeared to be minimal with D-23129. The percent mean total radioactivity not associated with the parent compound recovered from oxidative metabolism studies from three individual liver donors was 0.7%+/-0.6% SD and was not significantly different from [C-14]-D-23129 incubated with heat inactivated microsomes, mean = 0.5%+/-0.4 SD. 3. Phase II conjugation dominated the metabolism of D-23129 producing two distinct N-glucuronides as the primary metabolites. These metabolites were identified by electrospray ionization LC/MS. 4. The apparent K-m for one of the glucuronide metabolites was determined in human liver microsome preparations from two individual liver donors to be 131 and 264 mu m respectively. V-max determined for the same microsomal preparations yielded 48.9 and 59.9 pmol/min/mg protein. C1 NATL INST NEUROL DISORDERS & STROKE,PRECLIN PHARMACOL SECT,EPILEPSY BRANCH,NATL INST HLTH,ROCKVILLE,MD 20857. RP McNeilly, PJ (reprint author), US FDA,LAB CLIN PHARMACOL,OFF PHARMACEUT SCI,CTR DRUG EVALUAT & RES,LAUREL,MD 20708, USA. NR 22 TC 25 Z9 25 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD MAY PY 1997 VL 27 IS 5 BP 431 EP 441 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA XA423 UT WOS:A1997XA42300003 PM 9179986 ER PT J AU Dixon, DO AF Dixon, DO TI An overview of statistical methods for multiple failure time data in clinical trials - Discussion SO STATISTICS IN MEDICINE LA English DT Editorial Material RP Dixon, DO (reprint author), NIAID,SOLAR BLDG,ROOM 2B21,6003 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 2 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 APR 30 PY 1997 VL 16 IS 8 BP 843 EP 845 PG 3 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 WY902 UT WOS:A1997WY90200005 ER PT J AU Balajee, AS May, A Dianov, GL Friedberg, EC Bohr, VA AF Balajee, AS May, A Dianov, GL Friedberg, EC Bohr, VA TI Reduced RNA polymerase II transcription in intact and permeabilized cockayne syndrome group B cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CYCLOBUTANE PYRIMIDINE DIMERS; DNA-REPAIR; PREFERENTIAL REPAIR; GENE; FIBROBLASTS; RADIATION; EXTRACT; DEFECT; DAMAGE; TFIIH AB Cockayne syndrome (CS) is characterized by increased photosensitivity, growth retardation, and neurological and skeletal abnormalities. The recovery of RNA synthesis is abnormally delayed in CS cells after exposure to UV radiation, Gene-specific repair studies have shown a defect in the transcription-coupled repair (TCR) of active genes in CS cells from genetic complementation groups A and B (CS-A and CS-B), We have analyzed transcription in vivo in intact and permeabilized CS-B cells, Uridine pulse labeling in intact CS-B fibroblasts and lymphoblasts shows a reduction of approximate to 50% compared with various normal cells anal with cells from a patient with xeroderma pigmentosurn (XP) group A. In permeabilized CS-B cells transcription in chromatin isolated under physiological conditions is reduced to about 50% of that in normal chromatin and there is a marked reduction in fluorescence intensity in transcription sites in interphase nuclei, Transcription in CS-B cells is sensitive to alpha-amanitin, suggesting that it is RNA polymerase II-dependent, The reduced transcription in CS-B cells is complemented in chromatin by the addition of normal cell extract, and in intact cells by transfection with the CSR gene. CS-B may be a primary transcription deficiency. C1 NIA,GENET MOL LAB,NIH,BALTIMORE,MD 21224. UNIV TEXAS,SW MED CTR,DEPT PATHOL,LAB MOL PATHOL,DALLAS,TX 75235. NR 38 TC 126 Z9 127 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 29 PY 1997 VL 94 IS 9 BP 4306 EP 4311 DI 10.1073/pnas.94.9.4306 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WX362 UT WOS:A1997WX36200015 PM 9113985 ER PT J AU Meiri, N Ghelardini, C Tesco, G Galeotti, N Dahl, D Tomsic, D Cavallaro, S Quattrone, A Capaccioli, S Bartolini, A Alkon, DL AF Meiri, N Ghelardini, C Tesco, G Galeotti, N Dahl, D Tomsic, D Cavallaro, S Quattrone, A Capaccioli, S Bartolini, A Alkon, DL TI Reversible antisense inhibition of Shaker-like Kv1.1 potassium channel expression impairs associative memory in mouse and rat SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DROSOPHILA; BRAIN; POTENTIATION; HIPPOCAMPUS; DEPRESSION; REGIONS; KINASE; FAMILY; GENES; MICE AB Long-term memory is thought to be subserved by functional remodeling of neuronal circuits, Changes in the weights of existing synapses in networks might depend on voltage-gated potassium currents, We therefore studied the physiological role of potassium channels in memory, concentrating on the Shaker-like Kv1.1, a later rectifying potassium channel that is highly localized within dendrites of hippocampal CA3 pyramidal and dentate gyrus granular cells. Repeated intracerebroventricular injection of antisense oligodeoxyribonucleotide to Kv1.1 reduces expression of its particular intracellular mRNA target, decreases late rectifying K+ current(s) in dentate granule cells, and impairs memory but not other motor or sensory behaviors, in two different learning paradigms, mouse passive avoidance and rat spatial memory. The latter, hippocampal-dependent memory loss occurred in the absence of long-term potentiation changes recorded both From the dentate gyrus or CA1. The specificity of the reversible antisense targeting of mRNA in adult animal brains may avoid irreversible developmental and genetic background effects that accompany transgenic ''knockouts''. C1 UNIV FLORENCE,DEPT PHARMACOL,I-50134 FLORENCE,ITALY. UNIV FLORENCE,INST GEN PATHOL,I-50134 FLORENCE,ITALY. RP Meiri, N (reprint author), NIH,LAB ADAPT SYST,BETHESDA,MD 20892, USA. RI Cavallaro, Sebastiano/F-3104-2010; Galeotti, Nicoletta/N-1093-2015; OI Cavallaro, Sebastiano/0000-0001-7590-1792; Galeotti, Nicoletta/0000-0002-1812-9844; Quattrone, Alessandro/0000-0003-3333-7630 NR 28 TC 67 Z9 67 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 29 PY 1997 VL 94 IS 9 BP 4430 EP 4434 DI 10.1073/pnas.94.9.4430 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WX362 UT WOS:A1997WX36200036 PM 9114006 ER PT J AU Karayiorgou, M Altemus, M Galke, BL Goldman, D Murphy, DL Ott, J Gogos, JA AF Karayiorgou, M Altemus, M Galke, BL Goldman, D Murphy, DL Ott, J Gogos, JA TI Genotype determining low catechol-O-methyltransferase activity as a risk factor for obsessive-compulsive disorder SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID METABOLITES; SEROTONIN; RELATIVES; CLEARANCE; DOPAMINE; CLONING; BRAIN; LIVER AB In the present study, we address the role of the gene for catechol-O-methyltransferase (COMT), a key modulator of dopaminergic and noradrenergic neurotransmission, in the genetic predisposition to obsessive-compulsive disorder (OCD), We show that a common functional allele of this gene, which results in a 3- to 4-fold reduction in enzyme activity, is significantly associated in a recessive manner with susceptibility to OCD, particularly in males, This association is further supported by psychiatric evaluation of patients who carry microdeletions encompassing the comt gene, The mechanism underlying this sex-selective association remains to be defined and may include a sexual dimorphism in COMT activity, although close linkage with a nearby disease susceptibility locus cannot be excluded at this point. C1 CORNELL UNIV,COLL MED,DEPT PSYCHIAT,NEW YORK,NY 10021. NIAAA,NEUROGENET LAB,ROCKVILLE,MD 20852. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. COLUMBIA UNIV COLL PHYS & SURG,CTR NEUROBIOL & BEHAV,NEW YORK,NY 10032. RP Karayiorgou, M (reprint author), ROCKEFELLER UNIV,1230 YORK AVE,BOX 313,NEW YORK,NY 10021, USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU NHGRI NIH HHS [R01 HG000008, HG00008] NR 42 TC 239 Z9 245 U1 3 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 29 PY 1997 VL 94 IS 9 BP 4572 EP 4575 DI 10.1073/pnas.94.9.4572 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WX362 UT WOS:A1997WX36200061 PM 9114031 ER PT J AU Reiter, Y DiCarlo, A Fugger, L Engberg, J Pastan, I AF Reiter, Y DiCarlo, A Fugger, L Engberg, J Pastan, I TI Peptide-specific killing of antigen-presenting cells by a recombinant antibody-toxin fusion protein targeted to major histocompatibility complex peptide class I complexes with T cell receptor-like specificity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE immunotoxin; targeted therapy ID TUMOR-INFILTRATING LYMPHOCYTES; MELANOMA; IDENTIFICATION; CODES AB Specificity in the immune system is dictated and regulated by specific recognition of peptide/major histocompatibility complex (MHC) complexes by the T cell receptor, Such peptide/MHC complexes are a desirable target for novel approaches in immunotherapy because of their highly restricted fine specificity. Recently, phage display was used to isolate an antibody that has T cell receptor-like specificity, It recognizes mouse MHC class I H-2K(k) molecules complexed with a H-2K(k)-restricted influenza virus-derived hemagglutinin peptide (Ha(255-262)) but does not bind to class I H-2K(k) alone, peptide alone, or H-2K(k) complexed with other peptides, We have used this antibody to make a recombinant antibody-toxin fusion protein (immunotoxin) and show herein that it specifically kills antigen-presenting cells in a peptide-dependent manner and with T cell receptor-like specificity, We find a striking correlation between the fine specificity of binding of the antibody and the cytotoxic activity of the recombinant immunotoxin. We also show specific killing of influenza virus infected target cells, The results suggest that it should be possible to develop novel immunotherapeutic strategies against human cancer by making recombinant antibodies that will recognize cancer-related peptides complexed with MHC class I molecules on the surface of cancer cells and using these to deliver toxins, radioisotopes, or cytotoxic drugs to the cancer cells. C1 NCI,MOL BIOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. ROYAL DANISH SCH PHARM,DEPT SCI BIOL,DK-2100 COPENHAGEN,DENMARK. NATL UNIV HOSP,DEPT CLIN IMMUNOL,DK-2200 COPENHAGEN N,DENMARK. NR 23 TC 33 Z9 33 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 29 PY 1997 VL 94 IS 9 BP 4631 EP 4636 DI 10.1073/pnas.94.9.4631 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WX362 UT WOS:A1997WX36200072 PM 9114042 ER PT J AU Kruk, PA Orren, DK Bohr, VA AF Kruk, PA Orren, DK Bohr, VA TI Telomerase activity is elevated in early S phase in hamster cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CENTROMERES; DNA AB Telomerase is a ribonucleoprotein that elongates telomeric repeats de novo. We examined the possibility that telomerase activity is cell cycle regulated by examining telomerase activity in cell cycle synchronized Chinese hamster ovary (CHO) B11 cells. Overall telomerase activity was similar in growing and quiescent cells. Further, cells synchronized in G(1), S, or G(2)/M showed similar levels of telomerase activity. However, a detailed analysis of cells within S phase showed that there was a higher level of telomerase activity in early S phase when compared with other points in the cell cycle, These results suggest a relationship between telomerase activity and cell cycle regulation. (C) 1997 Academic Press. C1 NIA,GENET MOL LAB,NIH,BALTIMORE,MD 21224. RP Kruk, PA (reprint author), UNIV S FLORIDA,DEPT PATHOL,12901 BRUCE B DOWNS BLVD,TAMPA,FL 33612, USA. RI Kruk, Patricia/I-6489-2012 NR 19 TC 19 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 28 PY 1997 VL 233 IS 3 BP 717 EP 722 DI 10.1006/bbrc.1997.6549 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WX538 UT WOS:A1997WX53800028 PM 9168921 ER PT J AU Beamer, BA Negri, C Yen, CJ Gavrilova, O Rumberger, JM Durcan, MJ Yarnall, DP Hawkins, AL Griffin, CA Burns, DK Roth, J Reitman, M Shuldiner, AR AF Beamer, BA Negri, C Yen, CJ Gavrilova, O Rumberger, JM Durcan, MJ Yarnall, DP Hawkins, AL Griffin, CA Burns, DK Roth, J Reitman, M Shuldiner, AR TI Chromosomal localization and partial genomic structure of the human peroxisome proliferator activated receptor-gamma (hPPAR gamma) gene SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ADIPOCYTE DIFFERENTIATION; INSITU HYBRIDIZATION; PPAR-GAMMA; EXPRESSION; THIAZOLIDINEDIONE; PPAR-GAMMA-2; LIGAND; CELLS; J(2) AB We determined the chromosomal localization and partial genomic structure of the coding region of the human PPAR gamma gene (hPPAR gamma), a nuclear receptor important for adipocyte differentiation and function, Sequence analysis and long PCR of human genomic DNA with primers that span putative introns revealed that intron positions and sizes of hPPAR gamma are similar to those previously determined for the mouse PPAR gamma gene[la]. Fluorescent in situ hybridization localized hPPAR gamma tee chromosome 3, band 3p25, Radiation hybrid mapping with two independent primer pairs was consistent with hPPAR gamma being within 1.5 Mb of marker D3S1263 on 3p25-p24.2. These sequences of the intron/exon junctions of the 6 coding exons shared by hPPAR gamma 1 and hPPAR gamma 2 will facilitate screening for possible mutations. Furthermore, D3S1263 is a suitable polymorphic marker for linkage analysis to evaluate PPAR gamma's potential contribution to genetic susceptibility to obesity, lipoatrophy, insulin resistance, and diabetes. (C) 1997 Academic Press. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD. NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. GLAXOWELLCOME,RES TRIANGLE PK,NC. RP Beamer, BA (reprint author), JOHNS HOPKINS UNIV,SCH MED,DIV GERIATR MED & GERONTOL,BALTIMORE,MD 21205, USA. RI Reitman, Marc/B-4448-2013; OI Reitman, Marc/0000-0002-0426-9475; YEN, CHUNG-JEN/0000-0001-5372-3657 FU NCI NIH HHS [2P30 CA06973]; NIA NIH HHS [T32 AG00120] NR 19 TC 59 Z9 64 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 APR 28 PY 1997 VL 233 IS 3 BP 756 EP 759 DI 10.1006/bbrc.1997.6540 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WX538 UT WOS:A1997WX53800035 PM 9168928 ER PT J AU Kuenzel, WJ Mccune, SK Talbot, RT Sharp, PJ Hill, JM AF Kuenzel, WJ Mccune, SK Talbot, RT Sharp, PJ Hill, JM TI Sites of gene expression for vasoactive intestinal polypeptide throughout the brain of the chick (Gallus domesticus) SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE circumventricular organs; visceral forebrain system; in situ hybridization histochemistry ID PIGEON COLUMBA-LIVIA; FLUID-CONTACTING NEURONS; CENTRAL-NERVOUS-SYSTEM; SUPRACHIASMATIC NUCLEUS; RAT-BRAIN; PREFRONTAL CORTEX; INCUBATION BEHAVIOR; PASSER-DOMESTICUS; MESSENGER-RNA; RETINOHYPOTHALAMIC PROJECTION AB The peptide neurotransmitter vasoactive intestinal polypeptide (VIP) has several important functions in vertebrates, particularly, influencing the neuroendocrine and autonomic nervous systems both in developing and in adult animals. To document potential brain areas that might play significant functional roles, the distribution of VIP mRNA was examined throughout the entire chick brain by using in situ hybridization histochemistry (ISHH). In addition, a VIP binding-site study was completed that focused on the lateral septal organ (LSO), a circumventricular organ of potential significance in avian species. The areas where VIP message was found included the olfactory bulbs, posterior hippocampus, parahippocampal area, hyperstriatum, archistriatum/nucleus (n.) taenia (amygdala), medial part of the LSO, organum vasculosum of the lamina terminalis, medial preoptic region, bed n. of the pallial commissure, anterior hypothalamic (hypo.) n., lateral hypo. area (most extensive and dense message), periventricular hypo. n., lateral to the paraventricular n., ventromedial hypo. n., stratum cellulare externum, inferior hypo. n., infundibular hypo. n., median eminence, three layers within the stratum griseum et fibrosum superficiale, area ventralis of Tsai, n. tegmenti pedunculopontinus pars compacta (substantia nigra), intercollicular n., central gray, locus ceruleus, parabrachial n., ventrolateral medulla, reticular pontine area, in and about the n. vestibularis descendens. When compared with immunocytochemistry that detected the presence of the peptide product VIP, more areas of the brain were found to contain perikarya expressing VIP by using ISHH, particularly in the telencephalon and the mesencephalon. VIP binding sites were found in the lateral portion of the LSO where the blood-brain barrier is not fully developed. Hence, the LSO was found to contain neural elements that synthesize as well as bind VIP. VIP appears to be a useful peptide for defining major components of the visceral forebrain system in birds. (C) 1997 Wiley-Liss, Inc. C1 UNIV MARYLAND,DEPT POULTRY SCI,COLLEGE PK,MD 20742. JOHNS HOPKINS UNIV,SCH MED,CMSC,DEPT PEDIAT,BALTIMORE,MD 21287. ROSLIN INST,DIV DEV & REPROD,ROSLIN EH25 9PS,MIDLOTHIAN,SCOTLAND. NICHHD,SECT DEV & MOL PHARMACOL,DEV NEUROBIOL LAB,NIH,BETHESDA,MD 20892. NR 95 TC 45 Z9 46 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 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD APR 28 PY 1997 VL 381 IS 1 BP 101 EP 118 DI 10.1002/(SICI)1096-9861(19970428)381:1<101::AID-CNE8>3.0.CO;2-5 PG 18 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA WU521 UT WOS:A1997WU52100008 PM 9087422 ER PT J AU Giri, A Slattery, JP Heneine, W Gessain, A Rivadeneira, E Desrosiers, RC Rosen, L Anthony, R Pamungkas, J Iskandriati, D Richards, AL Herve, V McClure, H OBrien, SJ Franchini, G AF Giri, A Slattery, JP Heneine, W Gessain, A Rivadeneira, E Desrosiers, RC Rosen, L Anthony, R Pamungkas, J Iskandriati, D Richards, AL Herve, V McClure, H OBrien, SJ Franchini, G TI The tax gene sequences form two divergent monophyletic lineages corresponding to types I and II of simian and human T-Cell leukemia lymphotropic viruses SO VIROLOGY LA English DT Article ID COMPLETE NUCLEOTIDE-SEQUENCE; TROPICAL SPASTIC PARAPARESIS; HTLV-II; LYMPHOMA VIRUS; STLV-I; PHYLOGENETIC ANALYSES; HUMAN-POPULATIONS; BLOOD-DONORS; DRUG-ABUSERS; ANTIBODIES AB Evolutionary associations of human and simian T-cell leukemia/lymphotropic viruses I and II (HTLV-I/II and STLV-I/II) are inferred from phylogenetic analysis of lax gene sequences. Samples studied consisted of a geographically diverse assemblage of viral strains obtained from 10 human subjects and 20 individuals representing 12 species of nonhuman primates. Sequence analyses identified distinct substitutions, which distinguished between viral types I and II, irrespective of host species. Phylogenetic reconstruction of nucleotide sequences strongly supported two major evolutionary groups corresponding to viral types I and II. With the type I lineage, clusters were composed of strains from multiple host species. A genetically diverse, monophyletic lineage consisting of eight new viral strains from several species of Asian macaques was identified. The second lineage consisted of a monophyletic assemblage of HTLV-II/STLV-II strains from Africa and the New World, including an isolate from a pygmy chimp (Pan paniscus) as an early divergence within the lineage. High levels of genetic variation among strains from Asian STLV-I macaque suggest the virus arose in Asia. Evidence of the origin of the type II virus is less clear, but diversity among HTLV-II variants from a single isolated population of Mbati villagers is suggestive but not proof of an African origin. (C) 1997 Academic Press. C1 NCI,BASIC RES LAB,NIH,BETHESDA,MD 20892. NCI,LAB GENOM DIVERS,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. CTR DIS CONTROL & PREVENT,RETROVIRUS DIS BRANCH,DIV VIRAL & RICKETTSIAL DIS,CTR INFECT DIS,ATLANTA,GA 30333. INST PASTEUR,UNITE EPIDEMIOL VIRUS ONCOGENES,F-75724 PARIS 15,FRANCE. INST PASTEUR,SERV INFORMAT SCI,F-75724 PARIS 15,FRANCE. HARVARD UNIV,SCH MED,DIV MICROBIOL,SOUTHBOROUGH,MA 01772. UNIV HAWAII,PACIFIC BIOMED RES CTR,HONOLULU,HI 96816. AMER UNIV CARIBBEAN,BELIZE CITY,BELIZE. BOGOR AGR UNIC,PRIMATE RES CTR,BOGOR,INDONESIA. INST PASTEUR,BANGUI,CENT AFR REPUBL. YERKES REG PRIMATE RES CTR,ATLANTA,GA 30322. USN,MED RES UNIT N2,APO,AP 96520. NR 58 TC 13 Z9 13 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 APR 28 PY 1997 VL 231 IS 1 BP 96 EP 104 DI 10.1006/viro.1997.8511 PG 9 WC Virology SC Virology GA WW957 UT WOS:A1997WW95700012 PM 9143307 ER PT J AU Krebsbach, PH Kuznetsov, SA Satomura, K Emmons, RVB Rowe, DW Robey, PG AF Krebsbach, PH Kuznetsov, SA Satomura, K Emmons, RVB Rowe, DW Robey, PG TI Bone formation in vivo: Comparison of osteogenesis by transplanted mouse and human marrow stromal fibroblasts SO TRANSPLANTATION LA English DT Article ID DIFFUSION-CHAMBERS; CELL-CULTURES; HEMATOPOIETIC MICROENVIRONMENT; PRECURSOR CELLS; IN-VIVO; CFU-F; RAT; DIFFERENTIATION; EXPRESSION; INVIVO AB Background. Marrow stromal fibroblasts (MSFs) are known to contain bone precursor cells. However, the osteogenic potential of human MSFs has been poorly characterized. The aim of this study was to compare the osteogenic capacity of mouse and human MSFs after implantation in vivo. Methods. After in vitro expansion, MSFs were loaded into a number of different vehicles and transplanted subcutaneously into immunodeficient mice. Results. Mouse MSFs transplanted within gelatin, polyvinyl sponges, and collagen matrices all formed a capsule of cortical-like bone surrounding a cavity with active hematopoiesis. In transplants of MSFs from transgenic mice harboring type I procollagen chloramphenicol acetyltransferase constructs, chloramphenicol acetyltransferase activity was maintained for up to 14 weeks, indicating prolonged bone formation by transplanted MSFs. New bone formation by human MSFs was more dependent on both the in vitro expansion conditions and transplantation vehicles. Within gelatin, woven bone was observed sporadically and only after culture in the presence of dexamethasone and L-ascorbic acid phosphate magnesium salt n-hydrate. Consistent bone formation by human MSFs was achieved only within vehicles containing hydroxyapatite/tricalcium phosphate ceramics (HA/TCP) in the form of blocks, powder, and HA/TCP powder-type I bovine fibrillar collagen strips, and bone was maintained for at least 19 weeks. Cells of the new bone were positive for human osteonectin showing their donor origin. HA/TCP powder, the HA/TCP powder-type I bovine fibrillar collagen strips, and HA/TCP powder held together with fibrin were easier to load and supported more extensive osteogenesis than HA/TCP blocks and thus may be more applicable for therapeutic use. Conclusions. In this article, we describe the differences in the requirements for mouse and human MSFs to form bone, and report the development of a methodology for the consistent in vivo generation of extensive bone from human MSFs. C1 NIDR,BONE RES BRANCH,NIH,BETHESDA,MD 20892. NIDR,DEV BIOL LAB,NIH,BETHESDA,MD 20892. UNIV CONNECTICUT,CTR HLTH,DEPT PEDIAT,STORRS,CT 06269. UNIV CONNECTICUT,CTR HLTH,DEPT PEDIAT,STORRS,CT 06030. NHLBI,HEMATOL BRANCH,NIH,BETHESDA,MD 20892. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 55 TC 366 Z9 379 U1 0 U2 18 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 1997 VL 63 IS 8 BP 1059 EP 1069 DI 10.1097/00007890-199704270-00003 PG 11 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA WW660 UT WOS:A1997WW66000003 PM 9133465 ER PT J AU Poulter, NR Chang, CL Farley, TMM Kelaghan, J Meirlk, O Marmot, MG DebertRibeiro, M Medina, E Artigas, J He, S Zhong, YH Zhang, DW Zhao, WJ Rojas, O Heinemann, L Donnan, S Ho, S Bartfai, G Kisjanto, J Wilks, R Agwanda, R Ruiz, R KozuhNovak, M Dusitsin, N Virutamasen, P Phanthumchinda, K Koetsawang, S PiyaAnant, M Vessey, M Demirovic, J Belkic, K Mwandila, WS Mutale, CM Matenga, J Wilson, A Vessey, MP Petitti, D Perlman, J Kelaghan, J Holck, S Lawley, S Smith, S Shipley, M Olsen, J Thorogood, M AF Poulter, NR Chang, CL Farley, TMM Kelaghan, J Meirlk, O Marmot, MG DebertRibeiro, M Medina, E Artigas, J He, S Zhong, YH Zhang, DW Zhao, WJ Rojas, O Heinemann, L Donnan, S Ho, S Bartfai, G Kisjanto, J Wilks, R Agwanda, R Ruiz, R KozuhNovak, M Dusitsin, N Virutamasen, P Phanthumchinda, K Koetsawang, S PiyaAnant, M Vessey, M Demirovic, J Belkic, K Mwandila, WS Mutale, CM Matenga, J Wilson, A Vessey, MP Petitti, D Perlman, J Kelaghan, J Holck, S Lawley, S Smith, S Shipley, M Olsen, J Thorogood, M TI Acute myocardial infarction and combined oral contraceptives: Results of an international multicentre case-control study SO LANCET LA English DT Article ID YOUNG-WOMEN; CARDIOVASCULAR-DISEASE; RISK-FACTORS; DEATH AB Background The association between oral contraceptive (OC) use and acute myocardial infarction (AMI) was established in studies from northern Europe and the USA, which took place during the 1960s and 1970s. Few data are available to quantify the risk worldwide of AMI associated with use of OCs introduced since those early studies. This hospital-based case-control study examined the association between a first AMI and current OC use in women from Africa, Asia, Europe, and Latin America (21 centres). Methods Cases were women aged 20-44 years who had definite or possible AMI (classified by history, electrocardiographic, and cardiac-enzyme criteria), who were admitted to hospital, and who survived for at least 24 h. Up to three hospital controls matched by 5-year age-band were recruited for each of the 368 cases (941 controls). All participants were interviewed while in hospital with the same questionnaire, which included information on medical and personal history, lifetime contraceptive use, and blood-pressure screening before the most recent episode of OC use. Odds ratios compared the risk of AMI in current OC users and in non-users (past users and never-users combined). Findings The overall odds ratio for AMI was 5.01 (95% CI 2.54-9.90) in Europe and 4.78 (2.52-9.07) in the non-European (developing) countries; however, these risk estimates reflect the frequent coexistence of other risk factors among OC users who have AMI. Very few AMIs were identified among women who had no cardiovascular risk factors and who reported that their blood pressure had been checked before OC use; odds ratios associated with OC use in such women were not increased in either Europe or the developing countries. Among OC users who smoked ten or more cigarettes per day, the odds ratios in Europe and in the developing countries were over 20. Similarly, among OC users with a history of hypertension (during pregnancy or at any other time), odds ratios were at least ten in both groups of countries, No consistent association between odds ratios for AMI and age of OC users or oestrogen dose was apparent in either group of countries, No significant increase in odds ratios was apparent with increasing duration of OC use among current users, and odds ratios were not significantly increased in women who had stopped using OCs, even after long exposure. The study had insufficient power to examine whether progestagen dose or type had any effect on AMI risk. Interpretation Current use of combined OCs is associated with an increased risk of AMI among women with known cardiovascular risk factors and among those who have not been effectively screened, particularly for blood pressure, AMI is extremely rare in younger (<35 years) non-smoking women who use OCs, and the estimated excess risk of AMI in such women in the European centres is about 3 per 10(6) woman-years. The risk is likely to be even lower if blood pressure is screened before, and presumably during, OC use. Only among older women who smoke is the degree of excess risk associated with OCs substantial (about 400 per 10(6) woman-years). C1 ESCOLA PAULISTA MED,BR-04023 SAO PAULO,BRAZIL. UNIV CHILE,ESCUELA SALUD PUBL,SANTIAGO,CHILE. NATL RES INST FAMILY PLANNING,BEIJING,PEOPLES R CHINA. SICHUAN FAMILY PLANNING RES INST,CHENGDU,PEOPLES R CHINA. SHANGHAI INST PLANNED PARENTHOOD RES,SHANGHAI,PEOPLES R CHINA. UNIV VALLE,FAC SALUD,CALI,COLOMBIA. ZENTRUM EPIDEMIOL & GESUNDHEITSFORSCH,BERLIN,GERMANY. CHINESE UNIV HONG KONG,SHATIN 100083,HONG KONG. ALBERT SZENT GYORGYI MED UNIV,H-6701 SZEGED,HUNGARY. UNIV INDONESIA,FAC MED,JAKARTA,INDONESIA. KENYA GOVT MED RES CTR,NAIROBI,KENYA. INTERUNIV MEXICANO INVEST EPIDEMIOL SALUD REPROD,DURANGO,MEXICO. UNIV W INDIES,TROP METAB RES UNIT,KINGSTON 7,JAMAICA. ESCUELA MED,VALPARAISO,CHILE. UNIV LJUBLJANA,INST PUBL HLTH,LJUBLJANA,SLOVENIA. CHULALONGKORN HOSP,BANGKOK,THAILAND. SIRIRAJ HOSP,BANGKOK,THAILAND. UNIV OXFORD,OXFORD,ENGLAND. UNIV BELGRADE,SCH MED,YU-11001 BELGRADE,YUGOSLAVIA. UNIV TEACHING HOSP,LUSAKA,ZAMBIA. UNIV ZIMBABWE,HARARE,ZIMBABWE. UNIV OXFORD,OXFORD OX1 2JD,ENGLAND. KAISER PERMANENTE,PASADENA,CA. NICHHD,BETHESDA,MD. AARHUS UNIV,DANISH EPIDMEIOL SCI CTR,DK-8000 AARHUS C,DENMARK. LONDON SCH HYG & TROP MED,LONDON WC1,ENGLAND. RP Poulter, NR (reprint author), UNIV LONDON UNIV COLL,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,TORRINGTON PL,LONDON WC1E 6BT,ENGLAND. NR 37 TC 235 Z9 236 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD APR 26 PY 1997 VL 349 IS 9060 BP 1202 EP 1209 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA WW717 UT WOS:A1997WW71700009 ER PT J AU OBrien, TR Winkler, C Dean, M Nelson, JAE Carrington, M Michael, NL White, GC AF OBrien, TR Winkler, C Dean, M Nelson, JAE Carrington, M Michael, NL White, GC TI HIV-1 infection in a man homozygous for CCR5 Delta 32 SO LANCET LA English DT Article C1 NCI,LAB GENOM DIVERS,US PHS,US DEPT HHS,BETHESDA,MD 20852. WALTER REED ARMY INST RES,DEPT RETROVIROL,ROCKVILLE,MD. UNIV N CAROLINA,DIV HEMATOL & ONCOL,CAPEL HILL SCH MED,CHAPEL HILL,NC. UNIV N CAROLINA,DIV HEMATOL & ONCOL,SCH MED,CHAPEL HILL,NC. UNIV N CAROLINA,LINEBERGER COMPREHENS CANC CTR,SCH MED,CHAPEL HILL,NC. RP OBrien, TR (reprint author), NCI,VIRAL EPIDEMIOL BRANCH,US PHS,US DEPT HHS,BETHESDA,MD 20852, USA. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 5 TC 213 Z9 216 U1 1 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD APR 26 PY 1997 VL 349 IS 9060 BP 1219 EP 1219 DI 10.1016/S0140-6736(97)24017-1 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA WW717 UT WOS:A1997WW71700013 PM 9130945 ER PT J AU Trach, DD Clemens, JD AF Trach, DD Clemens, JD TI Field trial of oral cholera vaccine in Vietnam - Reply SO LANCET LA English DT Letter C1 NICHHD,DIV EPIDEMIOL,BETHESDA,MD 20892. NATL INST HYG & EPIDEMIOL,HANOI,VIETNAM. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD APR 26 PY 1997 VL 349 IS 9060 BP 1253 EP 1254 DI 10.1016/S0140-6736(05)62450-6 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA WW717 UT WOS:A1997WW71700057 ER PT J AU Wilson, SI Phylip, LH Mills, JS Gulnik, SV Erickson, JW Dunn, BM Kay, J AF Wilson, SI Phylip, LH Mills, JS Gulnik, SV Erickson, JW Dunn, BM Kay, J TI Escape mutants of HIV-1 proteinase: Enzymic efficiency and susceptibility to inhibition SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY LA English DT Article DE mutant HIV proteinase; HIV proteinase; substrate specificity; inhibitor binding; (E-coli) ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROTEASE INHIBITORS; RATIONAL DESIGN; RESISTANCE; VARIANTS; INFECTION; ABT-538; VIRIONS; POTENT; DIMER AB Genes encoding a number of mutants of HIV-1 proteinase were sub-cloned and expressed in E. coli. The proteinases containing mutations of single residues (e.g., G48V, V82F, I84V and L90M) were purified and their catalytic efficiencies relative to that of wild-type proteinase were examined using a polyprotein (recombinant HIV-1 gag) substrate and several series of synthetic peptides based on the -Hydrophobic* Hydrophobic-, -Aromatic* Pro- and pseudo-symmetrical types of cleavage junction. The L90M proteinase showed only small changes, whereas the activity of the other mutant enzymes was compromised more severely, particularly towards substrates of the -Aromatic* Pro- and pseudo-symmetrical types The susceptibility of the mutants and the wild-type proteinase to inhibition by eleven different compounds was compared. The L90M proteinase again showed only marginal changes in its susceptibility to all except one of the inhibitors examined. The K-i values determined for one inhibitor (Ro31-8959) showed that its potency towards the V82F, L90M, I84V and G48V mutant proteinases respectively was 2-, 3-, 17- and 27-fold less than against the wild-type proteinase. Several of the other inhibitors examined form a systematic series with Ro31-8959. The inhibition constants derived with these and a number of other inhibitors, including ABT-538 and L-735,524, are used in conjunction with the data on enzymic efficiency to assess whether each mutation in the proteinase confers an advantage for viral replication in the presence of any given inhibitor. C1 UNIV WALES COLL CARDIFF, SCH MOL & MED BIOSCI, CARDIFF CF1 3US, S GLAM, WALES. ROCHE RES CTR, WELWYN GARDEN CITY AL7 3AY, HERTS, ENGLAND. NCI, FREDERICK CANC RES & DEV CTR, STRUCT BIOCHEM PROGRAM, FREDERICK, MD 21702 USA. UNIV FLORIDA, J HILLIS MILLER HLTH CTR, DEPT BIOCHEM & MOL BIOL, GAINESVILLE, FL 32610 USA. FU NIAID NIH HHS [AI-28571] NR 40 TC 39 Z9 40 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4838 J9 BBA-PROTEIN STRUCT M JI Biochim. Biophys. Acta-Protein Struct. Molec. Enzym. PD APR 25 PY 1997 VL 1339 IS 1 BP 113 EP 125 DI 10.1016/S0167-4838(96)00224-5 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WX533 UT WOS:A1997WX53300015 PM 9165106 ER PT J AU Chang, MCJ Arai, T Freed, LM Wakabayashi, S Channing, MA Dunn, BB Der, MG Bell, JM Sasaki, T Herscovitch, P Eckelman, WC Rapoport, SI AF Chang, MCJ Arai, T Freed, LM Wakabayashi, S Channing, MA Dunn, BB Der, MG Bell, JM Sasaki, T Herscovitch, P Eckelman, WC Rapoport, SI TI Brain incorporation of [1-C-11]arachidonate in normocapnic and hypercapnic monkeys, measured with positron emission tomography SO BRAIN RESEARCH LA English DT Article DE positron emission tomography; arachidonate; brain; blood flow; phospholipid metabolism; monkey; rat; primate; imaging; signal transduction; radiotracer; lipid ID CEREBRAL BLOOD-VOLUME; RADIOLABELED FATTY-ACIDS; AWAKE RATS; CHOLINERGIC STIMULATION; PALMITATE INCORPORATION; UNANESTHETIZED RATS; ARACHIDONIC-ACID; 2ND MESSENGERS; CARBON-DIOXIDE; PHOSPHOLIPIDS AB Positron emission tomography (PET) was used to determine brain incorporation coefficients k* of [1-C-11]arachidonate in isoflurane-anesthetized rhesus monkeys, as well as cerebral blood flow (CBF) using [O-15]water. Intravenously injected [1-C-11]arachidonate disappeared from plasma with a half-life of 1.1 min, whereas brain radioactivity reached a steady-state by 10 min. Mean values of k* were the same whether calculated by a single-time point method at 20 min after injection began, or by least-squares fitting of an equation for total brain radioactivity to data at all time points. k* equalled 1.1-1.2 X 10(-4) ml.s(-1).g(-1) in gray matter and was unaffected by a 2.6-fold increase in CBF caused by hypercapnia. These results indicate that brain incorporation of [1-C-11]arachidonate can be quantified in the primate using PET, and that incorporation is flow-independent. C1 TOKYO MED & DENT UNIV, DEPT NEUROSURG, TOKYO 113, JAPAN. NIH, CTR CLIN, PET DEPT, BETHESDA, MD 20892 USA. TOKYO METROPOLITAN INST GERONTOL, PET MED CTR, TOKYO, JAPAN. RP NIA, NEUROSCI LAB, NIH, BLDG 10, ROOM 6C103, BETHESDA, MD 20892 USA. NR 55 TC 48 Z9 48 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD APR 25 PY 1997 VL 755 IS 1 BP 74 EP 83 DI 10.1016/S0006-8993(97)00088-7 PG 10 WC Neurosciences SC Neurosciences & Neurology GA WX074 UT WOS:A1997WX07400008 PM 9163542 ER PT J AU Sherman, ME Schiffman, MH Lorincz, AT Herrero, R Hutchinson, ML Bratti, C Zahniser, D Morales, J Hildesheim, A Helgesen, K Kelly, D Alfaro, M Mena, F Balmaceda, I Mango, L Greenberg, M AF Sherman, ME Schiffman, MH Lorincz, AT Herrero, R Hutchinson, ML Bratti, C Zahniser, D Morales, J Hildesheim, A Helgesen, K Kelly, D Alfaro, M Mena, F Balmaceda, I Mango, L Greenberg, M TI Cervical specimens collected in liquid buffer are suitable for both cytologic screening and ancillary human papillomavirus testing SO CANCER CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT 14th International Papillomavirus Conference CY JUL 21-28, 1995 CL QUEBEC CITY, CANADA DE cervix; Bethesda System; carcinoma; human papillomavirus; hybridization; atypical squamous cells of undetermined significance ID HYBRID CAPTURE; INTRAEPITHELIAL NEOPLASIA; SMEARS; WOMEN; MANAGEMENT; INFECTION; DIAGNOSIS; CANCER AB BACKGROUND. Several new techniques have been developed to improve the sensitivity of cervical carcinoma screening and reduce equivocal cytologic diagnoses referred to as atypical squamous cells of undetermined significance (ASCUS). This study evaluates the effectiveness of combining two newly introduced diagnostic techniques: preparation of thin-layer cytologic slides from ThinPrep liquid buffer and selected Hybrid Capture testing for human papillomavirus (HPV) DNA. Because HPV DNA detection has been strongly associated with the presence of a cervical carcinoma precursor (''squamous intraepithelial lesion,'' or SIL), HPV testing might be useful for identifying women with ASCUS who have an underlying SIL. METHODS. Two hundred specimens demonstrating diverse cervical abnormalities were selected from a prospective population-based study of 9174 women conducted in Costa Rica. The entire cohort had been screened with conventional cervical smears; ThinPrep slides made from liquid buffer; PAPNET, a computerized slide reading system; and Cervicography. Patients with any abnormal screening test were referred for colposcopy, punch biopsy, and loop excision of cases with high grade cytologic abnormalities not explained by punch biopsy. For this investigation, the results of ThinPrep cytology and HPV testing alone and in combination were compared with the final diagnoses, with an emphasis on the detection of carcinoma and high grade SIL. RESULTS. The 200 subjects studied included 7 women with a final diagnosis of carcinoma, 44 with high grade SIL, 34 with low grade SIL, 51 with a variety of equivocal diagnoses, and 64 with normal diagnoses. A ThinPrep cytologic diagnosis of SIL or carcinoma was made in 39 (76%) of the 51 women with final diagnoses of high grade SIL or carcinoma. Hybrid Capture testing detected carcinoma-associated types of HPV DNA in 100% of women with carcinoma, 75% with high grade SIL, 62% with low grade SIL, 20% with equivocal final diagnoses, and 12% of normal women. If colposcopy referral had been limited to women with a ThinPrep diagnosis of SIL or a diagnosis of ASCUS associated with the detection of carcinoma-associated HPV DNA from the same vial, 100% of women with carcinoma and 80% with high grade SIL would have been examined. To achieve this high sensitivity in the entire population of 9174 women would have required the referral of about 7% of the population. The combined screening strategy would have performed marginally better than optimized conventional screening with referral of any abnormal cytology (ASCUS and above). CONCLUSIONS. A cervical carcinoma screening technique which uses a single sample for cytopathology and HPV testing to triage equivocal diagnoses may be promising if it proves to be cost-effective. (C) 1997 American Cancer Society. C1 GEORGE WASHINGTON UNIV, MED CTR, DEPT PATHOL, WASHINGTON, DC 20037 USA. NCI, DIV EPIDEMIOL & GENET, BETHESDA, MD 20892 USA. DIGENE CORP, SILVER SPRING, MD USA. INT AGCY RES CANC, F-69372 LYON, FRANCE. TUFTS UNIV NEW ENGLAND MED CTR, DEPT PATHOL, BOSTON, MA 02111 USA. MINIST SALUD, SAN JOSE, COSTA RICA. CYTYC CORP, BOXBORO, MA USA. CAJA COSTARRICENSE SEGURO SOCIAL, SAN JOSE, COSTA RICA. INFORMAT MANAGEMENT SERV INC, SILVER SPRING, MD USA. NEUROMED SYST INC, SUFFERN, NY USA. UNIV PENN, GRAD HOSP, DEPT OBSTET & GYNECOL, PHILADELPHIA, PA 19104 USA. RP Sherman, ME (reprint author), JOHNS HOPKINS UNIV HOSP, DEPT PATHOL, 600 N WOLFE ST, ROOM 406, BALTIMORE, MD 21287 USA. FU NCI NIH HHS [N01-CP-21081, N01-CP-31061]; PHS HHS [163-MQ-440433] NR 31 TC 89 Z9 93 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1934-662X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD APR 25 PY 1997 VL 81 IS 2 BP 89 EP 97 PG 9 WC Oncology; Pathology SC Oncology; Pathology GA XP559 UT WOS:A1997XP55900002 PM 9126136 ER PT J AU Lazarovici, P Oshima, M Shavit, D Shibutani, M Jiang, H Monshipouri, M Fink, D Movsesyan, V Guroff, G AF Lazarovici, P Oshima, M Shavit, D Shibutani, M Jiang, H Monshipouri, M Fink, D Movsesyan, V Guroff, G TI Down-regulation of epidermal growth factor receptors by nerve growth factor in PC12 cells is p140(trk)-, Ras-, and Src-dependent SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; NEURONAL DIFFERENTIATION; SIGNAL-TRANSDUCTION; TYROSINE KINASE; PHEOCHROMOCYTOMA CELLS; AFFINITY; BINDING; PHOSPHORYLATION; MODULATION; MECHANISM AB Nerve growth factor (NGF) treatment causes a profound down-regulation of epidermal growth factor receptors during the differentiation of PC12 cells. This process is characterized by a progressive decrease in epidermal growth factor (EGF) receptor level measured by I-125-EGF binding, tyrosine phosphorylation, and Western blotting. Treatment of the cells with NGF for 5 days produces a 95% reduction in the amount of [S-35]methionine-labeled EGF receptors. This down-regulation does not occur in PC12nnr5 cells, which lack the p140(trk) NGF receptor. However, in PC12nnr5 cells stably transfected with p140(trk), the NGF-induced heterologous down-regulation of EGF receptors is reconstituted in part. NGF-induced heterologous down-regulation, but not EGF-induced homologous down-regulation of EGF receptors, is blocked in Ras- and Src-dominant-negative PC12 cells. Treatment with either pituitary adenylate cyclase-activating peptide (PACAP) or staurosporine stimulates neurite outgrowth in PC12 cell variants, but neither induces down-regulation of EGF receptors. NGF treatment of PC12 cells in suspension induces downregulation of EGF receptors in the absence of neurite outgrowth. These results strongly suggest a p140(trk)-, Has- and Src-dependent mechanism of NGF-induced down-regulation of EGF receptors and separate this process from NGF-induced neurite outgrowth in PC12 cells. C1 NICHHD,GROWTH FACTORS SECT,NIH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. RI Shibutani, Makoto/C-2510-2013 NR 41 TC 27 Z9 27 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 APR 25 PY 1997 VL 272 IS 17 BP 11026 EP 11034 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WW009 UT WOS:A1997WW00900011 PM 9110995 ER PT J AU Wink, DA Cook, JA Kim, SY Vodovotz, Y Pacelli, R Krishna, MC Russo, A Mitchell, JB Jourdheuil, D Miles, AM Grisham, MB AF Wink, DA Cook, JA Kim, SY Vodovotz, Y Pacelli, R Krishna, MC Russo, A Mitchell, JB Jourdheuil, D Miles, AM Grisham, MB TI Superoxide modulates the oxidation and nitrosation of thiols by nitric oxide-derived reactive intermediates SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; PEROXYNITRITE; METALLOTHIONEIN; NITROSYLATION; INHIBITION; MECHANISM; KINETICS; CYSTEINE; CYCLASE; RELEASE AB Thiol-containing proteins are key to numerous cellular processes, and their functions can be modified by thiol nitrosation or oxidation. Nitrosation reactions are quenched by O-2(radical anion), while the oxidation chemistry mediated by peroxynitrite is quenched by excess flux of either NO or O-2(radical anion). A solution of glutathione (GSH), a model thiol containing tripeptide, exclusively yielded S-nitrosoglutathione when exposed to the NO donor, Et2NN(O)NONa. However, when xanthine oxidase was added to the same mixture, the yield of S-nitrosoglutathione dramatically decreased as the activity of xanthine oxidase increased, such that there was a 95% reduction in nitrosation when the fluxes of NO and O-2(radical anion) were nearly equivalent. The presence of superoxide dismutase reversed O-2(radical anion)-mediated inhibition, while catalase had no effect. Increasing the flux of O-2(radical anion) yielded oxidized glutathione (GSSG), peaking when the flux of NO and O-2(radical anion) were approximately equivalent. The results suggest that oxidation and nitrosation of thiols by superoxide and NO are determined by their relative fluxes and may have physiological significance. C1 LOUISIANA STATE UNIV,MED CTR,DEPT PHYSIOL,SHREVEPORT,LA 71130. GRAMBLING STATE UNIV,DEPT CHEM,GRAMBLING,LA 71245. RP Wink, DA (reprint author), NCI,RADIAT BIOL BRANCH,TUMOR BIOL SECT,NIH,BLDG 10,RM B3-B69,BETHESDA,MD 20892, USA. NR 29 TC 149 Z9 154 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 25 PY 1997 VL 272 IS 17 BP 11147 EP 11151 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WW009 UT WOS:A1997WW00900028 PM 9111012 ER PT J AU Pribluda, VS Pribluda, C Metzger, H AF Pribluda, VS Pribluda, C Metzger, H TI Biochemical evidence that the phosphorylated tyrosines, serines, and threonines on the aggregated high affinity receptor for IgE are in the immunoreceptor tyrosine-based activation motifs SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL ANTIGEN RECEPTOR; IMMUNOGLOBULIN-E; SIGNAL-TRANSDUCTION; PROTEIN; KINASES; PATHWAYS; LYN; SYK; ENGAGEMENT; COMPLEX AB Activation of cells mediated by the high affinity receptor for IgE leads to rapid phosphorylation of tyrosines (and later other residues) on the receptor's beta and gamma subunits, and there is circumstantial evidence that the tyrosines modified are in the so-called immunoreceptor tyrosine based activation motifs (ITAMs). We identified and quantitated the residues phosphorylated on the subunits of the native receptor by comparing the properties of peptides derived from the receptors radiolabeled in vivo or in vitro with those of synthetic peptides, Our results with receptors labeled in vivo confirm that only the tyrosines in the ITAMs of beta and gamma became phosphorylated, and preferentially, those in the canonical YXX(L/I) sequences, The extent of phosphorylation of the canonical tyrosines was of the same order of magnitude, but the amino terminal canonical tyrosine in the ITAM of the beta subunit was consistently phosphorylated to a lesser degree, The non-canonical ITAM tyrosine in the beta subunit was considerably less phosphorylated, Phosphorylation of serine (on beta) and threonine (on gamma) also occurred mainly in the ITAMs, but selectively at some positions whose characteristics seem to be conserved among other receptors containing ITAMs. The studies with receptor complexes isolated and radiolabeled in vitro gave similar results for phosphorylation of tyrosines, suggesting that the latter, much simpler system is a useful model for more detailed studies. C1 NIAMS,ARTHRIT & RHEUMATISN BRANCH,NIH,BETHESDA,MD 20892. NR 35 TC 23 Z9 23 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 APR 25 PY 1997 VL 272 IS 17 BP 11185 EP 11192 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WW009 UT WOS:A1997WW00900034 PM 9111018 ER PT J AU Zolotukhin, AS Felber, BK AF Zolotukhin, AS Felber, BK TI Mutations in the nuclear export signal of human Ran-binding protein RanBP1 block the Rev-mediated posttranscriptional regulation of human immunodeficiency virus type 1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATION DOMAIN; IDENTIFICATION; RAN/TC4; CELLS; EXPRESSION; MUTANTS; YEAST; RNA; NUCLEOPORIN; TRAFFICKING AB We identified a region in the human Ran GTPase-binding protein RanBP1 that shares similarities to the nuclear export signal of the inhibitor of the cAMP-dependent protein kinase. Mutational analysis confirmed that this region is responsible for the cytoplasmic accumulation of RanBP1 and can functionally replace the nuclear export signal of Rev of human immunodeficiency virus type 1. We showed that RanBP1 interferes with Rev-mediated expression of human immunodeficiency virus type 1, whereas the RanBP1 with inactivated nuclear export signal abrogates Rev function. Expression of a Rev-independent molecular clone, which is regulated via the constitutive transport element (CTE) of the simian retrovirus type 1, is not affected. These findings indicate that Rev and RanBP1 compete for the same nuclear export pathway, whereas Rev- and the CTE mediated pathways are distinct. The inhibition of Rev function is independent of the ability of RanBP1 to associate with Ran and therefore, it is not likely a result of interference with Ran function. These data suggest that RanBP1 interacts with Rev at the putative nuclear receptor and, hence, shares a step in posttranscriptional pathway with Rev. C1 NCI,HUMAN RETROVIRUS PATHOGENESIS GRP,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 36 TC 45 Z9 45 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 APR 25 PY 1997 VL 272 IS 17 BP 11356 EP 11360 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WW009 UT WOS:A1997WW00900059 PM 9111043 ER PT J AU Garside, D Goldberger, BA Preston, KL Cone, EJ AF Garside, D Goldberger, BA Preston, KL Cone, EJ TI Rapid liquid-liquid extraction of cocaine from urine for gas chromatographic mass spectrometric analysis SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE cocaine ID SOLID-PHASE EXTRACTION; ECGONINE METHYL-ESTER; ARRAY DETECTION; AMNIOTIC-FLUID; BODY-FLUIDS; BENZOYLECGONINE; METABOLITES; CONFIRMATION; NORCOCAINE; PRODUCTS AB A novel, simple and economic liquid-liquid extraction method for isolating cocaine from urine was developed utilizing gas chromatography-mass spectrometry (CC-MS) for analysis and quantification. The use of a single nonpolar organic solvent allowed only nonpolar analytes to be extracted from the biological fluid, and consequently, no derivatization step was necessary before CC-MS analysis. Large numbers of specimens (>60) can be extracted in approximately 3 h with this procedure. The method is highly precise (C.V. <7%), accurate (>98%), sensitive (limit of detection of 5 ng/mI) and has a mean recovery of 48.8%. C1 UNIV FLORIDA,COLL MED,DIAGNOST REFERRAL LABS,GAINESVILLE,FL 32608. NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 NR 25 TC 10 Z9 10 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B PD APR 25 PY 1997 VL 692 IS 1 BP 61 EP 65 DI 10.1016/S0378-4347(96)00459-8 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WY409 UT WOS:A1997WY40900009 PM 9187384 ER PT J AU Hegedus, L Ford, H Hartman, NR Kelley, JA AF Hegedus, L Ford, H Hartman, NR Kelley, JA TI Reversed-phase high-performance liquid chromatographic determination of the new antitumor agent cyclopentenyl cytosine in biological fluids SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE cyclopentenyl cytosine ID CPE-C; CYTIDINE; TRIPHOSPHATE; NUCLEOSIDES; ANALOGS AB Cyclopentenyl cytosine (CPE-C) is a synthetic carbocyclic nucleoside that possesses diverse antitumor and antiviral activity. CPE-C has been studied extensively at the preclinical level and has been evaluated in a Phase I clinical trial involving patients with solid tumors. A narrow-bore, reversed-phase HPLC method that has been developed for the sensitive measurement of CPE-C in plasma and urine in order to carry out these studies is described. Covalent solid-phase extraction based on an immobilized phenylboronic acid ligand is employed to isolate both CPE-C and endogenous ribonucleosides from the biological matrix selectively and efficiently. This is followed by isocratic elution of the extract with pH 5.0, 0.1 M ammonium formate buffer at 0.150 ml/min on a tandem, switchable, C-18 narrow-bore (2.1 mm LD.) column system in which the precolumn is automatically backflushed to eliminate late-eluting components. UV detection at 278 nm provides a limit of quantitation of 0.1 mu M for CPE-C in rat and human plasma with a precision better than 4% for the range 1-20 mu M in rat plasma. Application of this assay to the determination of the bolus dose plasma kinetics and disposition of 2 mg/kg CPE-C in rats is illustrated. This method is amenable to partial automation and is well-suited for the analysis of clinical samples. C1 NCI,MED CHEM LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 31 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B PD APR 25 PY 1997 VL 692 IS 1 BP 169 EP 179 DI 10.1016/S0378-4347(96)00464-1 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WY409 UT WOS:A1997WY40900022 PM 9187397 ER PT J AU Kozikowski, AP Wang, SM Ma, DW Yao, JC Ahmad, S Glazer, RI Bogi, K Acs, P Modarres, S Lewin, NE Blumberg, PM AF Kozikowski, AP Wang, SM Ma, DW Yao, JC Ahmad, S Glazer, RI Bogi, K Acs, P Modarres, S Lewin, NE Blumberg, PM TI Modeling chemistry, and biology of the benzolactam analogues of indolactam V (ILV) .2. Identification of the binding site of the benzolactams in the CRD2 activator-binding domain of PKC delta and discovery of an ILV analogue of improved isozyme selectivity SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; TUMOR PROMOTERS; LYNGBYATOXIN-A; PHORBOL ESTERS; CONFORMATIONAL STATES; STRUCTURAL BASIS; TELEOCIDINS; CELLS; STEREOCHEMISTRY; REQUIREMENTS AB Protein kinase C (PKC) is a complex enzyme system comprised of at least II isozymes that serves to mediate numerous extracellular signals which generate lipid second messengers. The discovery of isozyme-selective activators and inhibitors (modulators) of PKC is crucial to ascertaining the role of the individual isozymes in physiological and pathophysiological processes and to manipulating their function. The discovery of such small molecule modulators of PKC is at present a largely unmet pharmacological need. Herein we detail our modeling studies which reveal how the natural product indolactam V (ILV) and its 8-membered ring analogue, the benzolactam 15, bind to the CRD2 activator domain of PKC. These modeling studies reveal that not all PKC ligands possess a common pharmacophore, and further suggest an important role of specific hydrophobic contacts in the PKC-ligand interaction, The modeling studies find strong experimental support from mutagenesis studies on PKC alpha that reveal the crucial role played by the residues proline 11, leucine 20, leucine 24, and glycine 27. Next, we describe the synthesis of two 8-substituted benzolactams starting from L-phenylalanine and characterize their isozyme selectivity; one of the two benzolactams exhibits improved isozyme selectivity relative to the n-octyl-ILV, Lastly, we report inhibition of cellular proliferation of two different breast carcinoma cell lines by the benzolactam 5 and show that the compound preferentially down-regulates PKC beta in both cell lines. C1 GEORGETOWN UNIV,MED CTR,DEPT PHARMACOL,WASHINGTON,DC 20007. CHINESE ACAD SCI,SHANGHAI INST ORGAN CHEM,SHANGHAI 200032,PEOPLES R CHINA. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,MOL MECHANISMS TUMOR PROMOT SECT,BETHESDA,MD 20892. RP Kozikowski, AP (reprint author), GEORGETOWN UNIV,MED CTR,INST COGNIT & COMPUTAT SCI,3970 RESERVOIR RD NW,WASHINGTON,DC 20007, USA. RI Wang, Shaomeng/E-9686-2010 NR 57 TC 73 Z9 76 U1 1 U2 4 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 APR 25 PY 1997 VL 40 IS 9 BP 1316 EP 1326 DI 10.1021/jm960875h PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA WW016 UT WOS:A1997WW01600002 PM 9135029 ER PT J AU Brinkmann, U DiCarlo, A Vasmatzis, G Kurochkina, N Beers, R Lee, B Pastan, I AF Brinkmann, U DiCarlo, A Vasmatzis, G Kurochkina, N Beers, R Lee, B Pastan, I TI Stabilization of a recombinant Fv fragment by base-loop interconnection and V-H-V-L permutation SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE antibody engineering; cancer therapy; anti-Tac; scFv; dsFv ID SINGLE-CHAIN FV; PSEUDOMONAS EXOTOXIN; ANTITUMOR-ACTIVITY; ESCHERICHIA-COLI; IMMUNOTOXIN; PROTEINS; ANTIBODY; BINDING; DOMAINS; FORMS AB We have developed a novel method to stabilize a recombinant antibody Fv fragment. The V-H and V-L domains of this Fv fragment, called pFv (permutated Fv), are covalently interconnected to each other at the two ''base-loops'' that normally connect V-H beta strand 3 to 3b and V-L beta strand 3 to 3b. To produce the base-loop stabilized Fv fragment, we connected the N-terminal half of the V-L domain (V-L 1-40) of murine antibody anti-Tac to the C-terminal half of V-H (V-H 42-115). We also fused the C terminus of V-H by a (Gly,Ser), Linker to the N-terminal half of V-H (V-H 1-40, thereby generating a permutated V-H domain). Finally we connected the base loop of V-H (N-terminal half) to the C-terminal half of V-L (V-H 42-115). The anti-Tac pFv fragment was fused to a truncated form of Pseudomonas exotoxin to generate a pFv-immunotoxin. Fvs with the correct structure were produced by refolding of recombinant inclusion body protein using a renaturation protocol that was originally developed for Fab and scFv fragments. Due to the artificially connected and permutated primary sequence, the folding pathway for the pFv structure may possibly be different from the conventional folding of antibody domains. Analysis of antigen binding of anti-Tac pFv, and of the specific cytotoxicity of pFv-immunotoxin towards antigen expressing cancer cells demonstrated that the anti-Tac pFv retained most of its affinity and full specificity when compared to anti-Tac scFv. Also anti-Tac pFv was relatively stable, retaining 25% of its binding activity after a 24 hour incubation in human serum at 37 degrees C. This indicates that connection of base loops can be a useful alternative to linker or disulfide stabilization of Fv fragments. C1 NCI,MOL BIOL LAB,NIH,BETHESDA,MD 20892. NR 32 TC 27 Z9 28 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD APR 25 PY 1997 VL 268 IS 1 BP 107 EP 117 DI 10.1006/jmbi.1996.0850 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WV871 UT WOS:A1997WV87100011 PM 9149145 ER PT J AU Dent, AL Shaffer, AL Yu, X Allman, D Staudt, LM AF Dent, AL Shaffer, AL Yu, X Allman, D Staudt, LM TI Control of inflammation, cytokine expression, and germinal center formation by BCL-6 SO SCIENCE LA English DT Article ID CENTER B-CELLS; NON-HODGKINS-LYMPHOMA; FINGER ENCODING GENE; TRANSCRIPTION FACTOR; PROTEIN; BINDING; SEQUENCE; LAZ3; IL-4; TRANSLOCATIONS AB The gene encoding the BCL-6 transcriptional repressor is frequently translocated and mutated in diffuse large cell lymphoma. Mice with a disrupted BCL-6 gene developed myocarditis and pulmonary vasculitis, had no germinal centers, and had increased expression of T helper cell type 2 cytokines. The BCL-6 DNA recognition motif resembled sites bound by the STAT (signal transducers and activators of transcription) transcription factors, which mediate cytokine signaling. BCL-6 could repress interleukin-4 (IL-4)-induced transcription when bound to a site recognized by the IL-4-responsive transcription factor Stat6. Thus, dysregulation of STAT-responsive genes may underlie the inflammatory disease in BCL-6-deficient mice and participate in lymphoid malignancies. C1 NCI,METAB BRANCH,NATL INST HLTH,BETHESDA,MD 20892. NCI,EXPT IMMUNOL BRANCH,NATL INST HLTH,BETHESDA,MD 20892. NR 38 TC 623 Z9 636 U1 1 U2 8 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD APR 25 PY 1997 VL 276 IS 5312 BP 589 EP 592 DI 10.1126/science.276.5312.589 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WV721 UT WOS:A1997WV72100044 PM 9110977 ER PT J AU AbuShakra, A Zeiger, E AF AbuShakra, A Zeiger, E TI Formation of 8-hydroxy-2'-deoxyguanosine following treatment of 2'-deoxyguanosine or DNA by hydrogen peroxide or glutathione SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE Salmonella; mutagenesis; oxidative damage ID OXIDATIVE DNA; SALMONELLA-TYPHIMURIUM; 8-HYDROXYGUANINE RESIDUES; DEOXYRIBONUCLEIC-ACID; PLUS LIGHT; L-CYSTEINE; LIVER DNA; ORGAN DNA; DAMAGE; 8-HYDROXYDEOXYGUANOSINE AB We have demonstrated that free radicals generated by hydrogen peroxide (H2O2), in the presence of divalent iron (Fe2+) and a chelator (EDTA), oxidize 2'-deoxyguanosine (dG) to 8-hydroxy-2'-deoxyguanosine (8-OHdG). The 8-OHdG formed by this reaction was isolated and quantitated using reverse-phase HPLC with UV and electrochemical detection. A 1-h incubation of dG with H2O2 caused a 50% increase in 8-OHdG over background, which increased to 100% after 2 h. However, when an H2O2-generating system [glutathione (GSH), Fe2+, EDTA] was used there was no increase in 8-OHdG yield after the 1-h incubation, but up to a 50% increase over background was observed with GSH after 2-h incubation. Attempts to detect increased levels of 8-OHdG after H2O2- or GSH-treatment of purified calf thymus or rat DNA, or purified Salmonella typhimurium DNA were not successful. This may have been because the treatment procedures used generated 8-OHdG in the control samples at sufficiently high levels to mask any H2O2-induced responses that may have been present. This artifactual production of 8-OHdG has presented a problem in all in vitro studies to date. In contrast, treatment of Salmonella cells (strain TA104) with increasing concentrations of H2O2, caused a doubling in the 8-OHdG yield. GSH-treatment of strain TA104 cells under the same conditions did not result in an increase of 8-OHdG. The study presented here: shows that the ubiquitous molecule H2O2 can play a major role in DNA oxidation, mutation, and damage. C1 NIEHS,ENVIRONM TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. NR 38 TC 13 Z9 13 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD APR 24 PY 1997 VL 390 IS 1-2 BP 45 EP 50 DI 10.1016/S0165-1218(96)00164-4 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA WV937 UT WOS:A1997WV93700006 PM 9150751 ER PT J AU MenottiRaymond, MA David, VA OBrien, SJ AF MenottiRaymond, MA David, VA OBrien, SJ TI Pet cat hair implicates murder suspect SO NATURE LA English DT Letter ID MICROSATELLITE LOCI; SINGLE HAIRS; HUMAN DNA C1 NCI,SAIC,FREDERICK,MD 21702. RP MenottiRaymond, MA (reprint author), NCI,LAB GENOM DIVERS,FREDERICK,MD 21702, USA. NR 14 TC 58 Z9 59 U1 1 U2 13 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD APR 24 PY 1997 VL 386 IS 6627 BP 774 EP 774 DI 10.1038/386774a0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WV706 UT WOS:A1997WV70600038 PM 9126735 ER PT J AU Borges, M Linnoila, RI vandeVelde, HJK Chen, H Nelkin, BD Mabry, M Baylin, SB Ball, DW AF Borges, M Linnoila, RI vandeVelde, HJK Chen, H Nelkin, BD Mabry, M Baylin, SB Ball, DW TI An achaete-scute homologue essential for neuroendocrine differentiation in the lung SO NATURE LA English DT Article ID SMALL-CELL CARCINOMA; CANCER; GROWTH; LINES; ESTABLISHMENT; IDENTIFICATION; EXPRESSION; ENDOCRINE; TUMORS AB In Drosophila and in vertebrates, the achaete-scute family of basic helix-loop-helix transcription factors plays a critical developmental role in neuronal commitment and differentiation(1-6). Relatively little is known, however about the transcriptional control of neural features in cells outside a neuronal context. A minority of normal bronchial epithelial cells and many Lung cancers, especially small-cell lung cancer, exhibit a neuroendocrine phenotype that may reflect a common precursor cell population(7-11). We show here that human achaete-scute homologue-1 (hASW1) is selectively expressed in normal fetal pulmonary neuroendocrine cells, as well as in the diverse range of lung cancers with neuroendocfine features. Strikingly, newborn mice bearing a disruption of the ASR1 gene have no detectable pulmonary neuroendocrine cells. Depletion of this transcription factor from lung cancer cells by antisense oligonucleotides results in a significant decrease in the expression of neuroendrocrine markers. Thus, a homologue of Drosophila neural fate determination genes seems to be necessary for progression of lung epithelial cells through a neuroendocrine differentiation pathway that is a feature of small-cell lung cancer, the most. lethal form of human lung cancer. C1 JOHNS HOPKINS MED INST, CTR ONCOL, BALTIMORE, MD 21231 USA. JOHNS HOPKINS MED INST, DEPT MED, BALTIMORE, MD 21231 USA. JOHNS HOPKINS MED INST, DEPT SURG, BALTIMORE, MD 21231 USA. NCI, MED BRANCH, DIV CLIN SCI, NIH, ROCKVILLE, MD 20850 USA. NR 30 TC 215 Z9 220 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 24 PY 1997 VL 386 IS 6627 BP 852 EP 855 DI 10.1038/386852a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WV706 UT WOS:A1997WV70600059 PM 9126746 ER PT J AU Kovacs, JA Davey, RT Lane, HC AF Kovacs, JA Davey, RT Lane, HC TI Interleukin-2 infusions in HIV-infected patients - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP Kovacs, JA (reprint author), NIH,BETHESDA,MD 20892, USA. NR 4 TC 4 Z9 4 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 APR 24 PY 1997 VL 336 IS 17 BP 1260 EP 1261 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA WV332 UT WOS:A1997WV33200030 ER PT J AU Gallahan, D Callahan, R AF Gallahan, D Callahan, R TI The mouse mammary tumor associated gene INT3 is a unique member of the NOTCH gene family (NOTCH4) SO ONCOGENE LA English DT Article DE INT3; NOTCH4; mammary tumor gene ID OF-SPLIT COMPLEX; DROSOPHILA NOTCH; NEUROGENIC LOCUS; MAMMALIAN NOTCH; HUMAN HOMOLOG; PROTEIN GENE; ENHANCER; RECEPTOR; EXPRESSION; SEQUENCE AB The INT3 gene is frequently rearranged in mouse mammary tumor virus (MMTV)-induced mammary tumors of the CzechII mouse strain, We have completed the nucleotide sequence of the normal 6.5 Kb INT3 RNA and defined the intron/exon boundaries of the gene, The open reading frame of INT3 RNA should encode a 200 kd protein which shares 60% homology with the mouse homologue of Drosophila NOTCH, INT3 is unique among other members of the NOTCH family by containing 29 instead of 36 EGF-like repeats in the extracellular domain of the gene product. Five novel EGF-like repeats have been created as consequence of apparent small deletions which have occurred within the coding region for the extracellular domain during evolution. Nucleotide sequence analysis of host-viral junction fragments from nine independent MMTV-induced mammary tumors containing a rearranged INT3 gene reveals that all of the integration events occur within a 174 bp region 3' of the sequences encoding the LIN12 repeats in the INT3 extracellular domain and 5' of the sequences encoding the transmembrane domain. Therefore, the only tumorigenic INT3 mutations resulting from MMTV proviral insertions are those which results in the expression of the intracellular domain. This strongly suggests that MMTV-induced activation of INT3 is manifest in the absence of the regulatory action of the extracellular domain, including the LIN12 repeat sequences, leaving the expressed intracellular domain constitutively free to function in its role in mammary tumorigenesis. C1 NCI,TUMOR IMMUNOL & BIOL LAB,NIH,BETHESDA,MD 20892. NR 50 TC 139 Z9 143 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 24 PY 1997 VL 14 IS 16 BP 1883 EP 1890 DI 10.1038/sj.onc.1201035 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA WV804 UT WOS:A1997WV80400001 PM 9150355 ER PT J AU Sei, Y Nishida, K Kustova, Y Markey, SP Morse, HC Basile, AS AF Sei, Y Nishida, K Kustova, Y Markey, SP Morse, HC Basile, AS TI Pentoxifylline decreases brain levels of platelet activating factor in murine AIDS SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE AIDS (acquired immunodeficiency syndrome); LP-BM5 murine leukemia virus; encephalopathy; PAF (platelet-activating factor); pentoxifylline; TNF-alpha (tumor necrosis factor-alpha) ID IMMUNODEFICIENCY; MODEL AB Tumor necrosis factor-alpha (TNF-alpha) and platelet-activating factor (PAF) have been implicated in the pathogenesis of human immunodeficiency virus (HIV)-associated encephalopathy. The effects of pentoxifylline on brain PAF levels were examined in mice infected with the LP-BM5 murine leukemia virus (MuLV). Seven weeks after viral inoculation, significant increases in serum TNF-alpha and brain PAF levels were observed, One week of treatment with pentoxifylline initiated 6 weeks postinfection significantly reduced both serum TNF-alpha and brain PAF levels. A significant positive correlation was observed between the levels of these substances (r = 0.62; P < 0.01). This study demonstrates that pentoxifylline treatment was effective in decreasing the levels of TNF-alpha in the serum and PAF levels in the brain of mice infected with the LP-BM5 MuLV. C1 NIAID,IMMUNOPATHOL LAB,NIH,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,NIH,BETHESDA,MD 20892. RP Sei, Y (reprint author), NIDDK,NEUROSCI LAB,NIH,BLDG 8,ROOM 111,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Morse, Herbert/0000-0002-9331-3705 NR 14 TC 6 Z9 6 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 APR 23 PY 1997 VL 325 IS 1 BP 81 EP 84 DI 10.1016/S0014-2999(97)89963-3 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WW591 UT WOS:A1997WW59100012 PM 9151942 ER PT J AU Fujita, M Enomoto, T Haba, T Nakashima, R Sasaki, M Yoshino, K Wada, H Buzard, GS Matsuzaki, N Wakasa, K Murata, Y AF Fujita, M Enomoto, T Haba, T Nakashima, R Sasaki, M Yoshino, K Wada, H Buzard, GS Matsuzaki, N Wakasa, K Murata, Y TI Alteration of p16 and p15 genes in common epithelial ovarian tumors SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID K-RAS ACTIVATION; HUMAN CANCERS; SUPPRESSOR GENE; HETEROZYGOSITY; METHYLATION; ADENOCARCINOMAS; INACTIVATION; CARCINOMAS; EXPRESSION; INHIBITOR AB We have examined the roles of 2 putative tumor-suppressor genes, the p16 and p15 inhibitor-of-cyclin-dependent-kinase genes, in the most commonly occurring epithelial tumors of the human ovary. Expression of p16 mRNA, examined by RT-PCR, was significantly reduced in 15 of the 48 tumors. Aberrant expression of p16 protein, detected by immunohistochemistry, occurred in 22 of 60 tumors, more frequently in low-grade tumors, and had significant correlation with low p16 mRNA expression. Hypermethylation of a site within the 5'-CpG island of the p16 gene was significantly associated with loss of p16 mRNA and protein expression. Homozygous gene deletion, evaluated by differential PCR analysis, was found in 2 tumors for the p16 gene and in 1 tumor for the p15 gene among 70 ovarian tumors examined. PCR-SSCP analysis detected point mutations in p16 in 4 tumors and in p15 in 1 tumor. One was a 38-bp deletion, from codons 48 to 60, in a mucinous tumor of low malignant potential; another was a non-sense mutation in codon 60 in a mucinous adenocarcinoma. The remaining 2 mutations were mis-sense mutations, one in codon 58 and the other in codon 60, in 2 endometrioid adenocarcinomas. We conclude that inactivation of p16 by loss of p16 mRNA and protein expression as a consequence of hypermethylation of the 5'-CpG island, rather than by gene deletion or point mutation, may play an important role in the genesis of human ovarian epithelial tumors. (C) 1997 Wiley-Liss, Inc. C1 OSAKA UNIV,FAC MED,DEPT OBSTET & GYNECOL,SCH MED,SUITA,OSAKA 565,JAPAN. OSAKA UNIV,DEPT PATHOL,SCH MED,SUITA,OSAKA 565,JAPAN. NCI,INTRAMURAL RES SUPPORT PROGRAM,SAIC FREDERICK,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701. NR 34 TC 48 Z9 51 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 22 PY 1997 VL 74 IS 2 BP 148 EP 155 DI 10.1002/(SICI)1097-0215(19970422)74:2<148::AID-IJC2>3.3.CO;2-9 PG 8 WC Oncology SC Oncology GA WX434 UT WOS:A1997WX43400002 PM 9133447 ER PT J AU Romeo, D Allison, RSH Kondaiah, P Wakefield, LM AF Romeo, D Allison, RSH Kondaiah, P Wakefield, LM TI Recharacterization of the start sites for the major human transforming growth factor-beta 1 mRNA SO GENE LA English DT Article DE ribonuclease protection assay; S1 nuclease protection assay; transcriptional promoter ID MESSENGER-RNA; PROMOTER; REGION; GENE AB The start sites for the major human TGF-beta 1 transcripts have been reexamined. A comparison of ribonuclease and SI nuclease protection analyses on native TGF-beta 1 mRNA and in vitro transcribed human TGF-beta 1 transcripts of defined sizes places the most 5' start site for the native TGF-beta 1 message approx. 50 nucleotides upstream from the previously published start site at base +1. Furthermore, the same techniques indicate that the apparent downstream start site at base +271 is an artefact due to the presence of an A + T-rich island in the middle of an otherwise highly G + C-rich sequence, This is not apparent if S1 nuclease protection is used alone, which emphasizes the importance of using the two techniques in combination for this type of analysis. Thus the major 2.5 kb TGF-beta 1 band seen on Northern blots comprises only mRNA transcribed from the more upstream of the two previously characterized promoters. This has important implications both for the transcriptional and translational regulation of this growth factor. (C) 1997 Elsevier Science B.V. C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NR 12 TC 8 Z9 11 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 APR 21 PY 1997 VL 189 IS 2 BP 289 EP 295 DI 10.1016/S0378-1119(96)00865-7 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA WX609 UT WOS:A1997WX60900020 PM 9168139 ER PT J AU Rajagopalan, S Long, EO AF Rajagopalan, S Long, EO TI The direct binding of a p58 killer cell inhibitory receptor to human histocompatibility leukocyte antigen (HLA)-Cw4 exhibits peptide selectivity SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HLA-C MOLECULES; MHC CLASS-I; B MOLECULES; NK CLONES; RECOGNITION; LYSIS; SPECIFICITIES; RESISTANCE; EXPRESSION; CLONING AB Natural killer (NK) cells in mice and humans express a number of structurally diverse receptors that inhibit target cell lysis upon recognition of major histocompatibility complex (MHC) class I molecules expressed on targets. The contribution of peptide to the structural features of class I required for NK cell inhibition appears to vary depending on the type of receptor engaged. Thus, while there is no peptide specificity in NK inhibition mediated by Ly-49A in the mouse, human histocompatibility antigen (HLA)-B*2705-specific NK clones displayed selectivity for peptides. In this report, we examine the role of peptide in the recognition of HLA-C by the defined killer cell inhibitory receptor (KIR) c142 with established specificity for HLA-Cw4. Binding of soluble KIR c142 molecules to HLA-Cw4 expressed on transporter associated with antigen presentation (TAP)-deficient RMA-S cells occurred only upon exogenous peptide loading. Moreover, there was peptide selectivity in that certain substitutions at positions 7 and 8 of the nonamer peptide QYDDAVYKL abolished Cw4 interaction with KIR c142 despite similar surface expression of HLA-C. The specificity of this direct interaction between peptide-loaded HLA-Cw4 on RMA-S cells and soluble KIR c142 correlated with recognition by NK clones in that they were inhibited only by HLA-Cw4 loaded with the appropriate peptides. C1 NIAID,IMMUNOGENET LAB,NIH TWINBROOK II,ROCKVILLE,MD 20852. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 31 TC 139 Z9 140 U1 0 U2 3 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 APR 21 PY 1997 VL 185 IS 8 BP 1523 EP 1528 DI 10.1084/jem.185.8.1523 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA WW047 UT WOS:A1997WW04700016 PM 9126935 ER PT J AU Sudhir, K Chou, TM Messina, LM Hutchison, SJ Korach, KS Chatterjee, K Rubanyi, GM AF Sudhir, K Chou, TM Messina, LM Hutchison, SJ Korach, KS Chatterjee, K Rubanyi, GM TI Endothelial dysfunction in a man with disruptive mutation in oestrogen-receptor gene SO LANCET LA English DT Article ID NORMAL MEN; ESTROGEN; WOMEN C1 UNIV CALIF SAN FRANCISCO,DEPT SURG,DIV VASC SURG,SAN FRANCISCO,CA 94143. NIEHS,RES TRIANGLE PK,NC 27709. BERLIEX BIOSCI,RICHMOND,CA. RP Sudhir, K (reprint author), UNIV CALIF SAN FRANCISCO,DEPT MED,DIV CARDIOL,SAN FRANCISCO,CA 94143, USA. NR 5 TC 117 Z9 120 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD APR 19 PY 1997 VL 349 IS 9059 BP 1146 EP 1147 DI 10.1016/S0140-6736(05)63022-X PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA WU544 UT WOS:A1997WU54400017 PM 9113019 ER PT J AU Yoshikawa, T Sanders, AR Esterling, LE Overhauser, J Garnes, JA Lennon, G Grewal, R DeteraWadleigh, SD AF Yoshikawa, T Sanders, AR Esterling, LE Overhauser, J Garnes, JA Lennon, G Grewal, R DeteraWadleigh, SD TI Isolation of chromosome 18-specific brain transcripts as positional candidates for bipolar disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE brain cDNA; cosmids; somatic cell hybrid; radiation hybrid; mapping; PCR ID CDNA LIBRARY; GENE; SEQUENCE; PROTEIN; HYBRIDIZATION; EXPRESSION; LINKAGE; MAP AB Several studies have proposed the existence of susceptibility loci for bipolar disorder on chromosome 18, To identify possible candidate genes for this disease, we isolated brain-expressed transcripts by direct cDNA selection on chromosome 18-specific biotinylated cosmid clones, Longer cognate cDNA clones of the selected cDNAs were isolated from a normalized infant brain cDNA library, Physical mapping by PCR on a panel of somatic cell hybrids was conducted by the use of primers derived from partial sequences on either the 5' or 3' ends of the clones, In our initial analysis, 48 cDNA clones were found to be chromosome 18-specific, mapping to different subchromosomal regions, Sequence redundancy among these clones yielded 30 unique transcripts, five of which were represented in previously known genes, Further sequencing of the remaining 25 unique cDNA clones confirmed the absence of significant homology to known genes, indicating that these transcripts represented novel genes, Mapping with the use of a radiation hybrid panel positioned the brain cDNAs to within approximate to 100 to 1100 kb from reference sequence tag sites (STSs) and assembled them into six high resolution linkage groups, The majority of the transcripts were found to cluster to discrete locations on 18p and 18q, previously hypothesized as susceptibility regions for bipolar disorder, identifying them as positional candidate genes. (C) 1997 Wiley-Liss, Inc. C1 NIMH,UNIT GENE MAPPING & EXPRESS,CLIN NEUROGENET BRANCH,NIH,BETHESDA,MD 20892. NIDOCD,GENET MOL LAB,NIH,BETHESDA,MD. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT BIOCHEM & MOL BIOL & MED GENET,PHILADELPHIA,PA 19107. LAWRENCE LIVERMORE NATL LAB,CTR HUMAN GENOME,LIVERMORE,CA. UNIV SO CALIF,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90033. FU NIA NIH HHS [P05-AG05142, K12 AG00521] NR 32 TC 15 Z9 15 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 APR 18 PY 1997 VL 74 IS 2 BP 140 EP 149 DI 10.1002/(SICI)1096-8628(19970418)74:2<140::AID-AJMG5>3.0.CO;2-Y PG 10 WC Genetics & Heredity SC Genetics & Heredity GA WV797 UT WOS:A1997WV79700005 PM 9129712 ER PT J AU Dean, M AF Dean, M TI Towards a unified model of tumor suppression: Lessons learned from the human patched gene SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review ID PROTEIN KINASE-A; BETA-CATENIN; DROSOPHILA HOMOLOG; SIGNALING PATHWAY; SONIC-HEDGEHOG; POLARITY; IDENTIFICATION; RETINOBLASTOMA; ASSOCIATION; INHIBITORS RP Dean, M (reprint author), NCI,HUMAN GENET SECT,LAB GENOM DIVERS,FREDERICK CANC RES & DEV CTR,BLD 560,RM 21-18,FREDERICK,MD 21702, USA. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 79 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD APR 18 PY 1997 VL 1332 IS 2 BP M43 EP M52 DI 10.1016/S0304-419X(96)00043-1 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA WY130 UT WOS:A1997WY13000001 PM 9141460 ER PT J AU Appel, NM Rapoport, SI OCallaghan, JP Bell, JM Freed, LM AF Appel, NM Rapoport, SI OCallaghan, JP Bell, JM Freed, LM TI Sequelae of parenteral domoic acid administration in rats: Comparison of effects on different metabolic markers in brain SO BRAIN RESEARCH LA English DT Article DE neurotoxicity; autoradiography; fatty acid; palmitic acid; arachidonic acid; 2-deoxyglucose; brain metabolism; gliosis; glial fibrillary acidic protein; seizure ID SUSTAINED ELECTRICAL-STIMULATION; MONKEYS MACACA-FASCICULARIS; TEMPORAL-LOBE EPILEPSY; KAINIC ACID; FATTY-ACIDS; UNANESTHETIZED RATS; HIPPOCAMPAL DAMAGE; REACTIVE GLIOSIS; PERFORANT PATH; AMINO-ACID AB Parenterally administered domoic acid, a structural analog of the excitatory amino acids glutamic acid and kainic acid, has specific effects on brain histology in rats, as measured usung different anatomic markers. Domoic acid-induced convulsions affects Limbic structures such as hippocampus and entorhinal cortex, and different anatomic markers can detect these neurotoxic effects to varying degrees, Here we report effects of domoic acid administration on quantitative indicators of brain metabolism and gliosis. Domoic acid, 2.25 mg/kg i.p., caused stereotyped behavior and convulsions in approximately 60% of rats which received it. Six to eight days after domoic acid or vehicle administration, the animals were processed to measure regional brain incorporation of the long-chain fatty acids [1-C-14]arachidonic acid ([C-14]AA) and [9,10-H-3]palmitic acid ([H-3]PA), or regional cerebral glucose utilization (rCMR(glc)) using 2-[1-C-14]deoxy-D-glucose, by quantitative autoradiography. Others rats were processed to measure brain glial fibrillary acidic protein (GFAP) by enzyme-linked immunosorbent assay. Domoic acid increased GFAP in the anterior portion of cerebral cortex, the caudate putamen and thalamus compared with vehicle. However, in rats that convulsed after domoic acid GFAP was significantly increased throughout the cerebral cortex, as well as in the hippocampus, septum, caudate putamen, and thalamus. Domoic acid, in the absence of convulsions, decreased relative [C-14]AA incorporation in the claustrum and pyramidal cell layer of the hippocampus compared with vehicle-injected controls, In the presence of convulsions, relative [C-14]AA incorporation was decreased in hippocampus regions CAl and CA2. Uptake of [H-3]PA into brain was unaffected. Relative rCMR(glc) decreased in entorhinal cortex following domoic acid administration with or without convulsions. These results suggest that acute domoic acid exposure affects discrete brain circuits by inducing convulsions, and that domoic acid-induced convulsions cause chronic effects on brain function that are reflected in altered fatty acid metabolism and gliosis. (C) 1977 Elsevier Science B.V. C1 NIA,NEUROSCI LAB,NIH,BETHESDA,MD 20892. US EPA,HLTH EFFECTS RES LAB,DIV NEUROTOXICOL,RES TRIANGLE PK,NC 27711. US FDA,CTR DRUG EVALUAT & RES,DIV NEUROPHARMACOL DRUG PROD,OFF DRUG EVALUAT 1,ROCKVILLE,MD 20852. RP Appel, NM (reprint author), US FDA,CTR DRUG EVALUAT & RES,DIV APPL PHARMACOL RES,OFF TESTING & RES,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. RI O'Callaghan, James/O-2958-2013 NR 62 TC 10 Z9 14 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 18 PY 1997 VL 754 IS 1-2 BP 55 EP 64 DI 10.1016/S0006-8993(97)00042-5 PG 10 WC Neurosciences SC Neurosciences & Neurology GA WW306 UT WOS:A1997WW30600007 PM 9134959 ER PT J AU Hickman, AB Waninger, S Scocca, JJ Dyda, F AF Hickman, AB Waninger, S Scocca, JJ Dyda, F TI Molecular organization in site-specific recombination: The catalytic domain of bacteriophage HP1 integrase at 2.7 angstrom resolution SO CELL LA English DT Article ID 4-WAY DNA JUNCTION; CRYSTAL-STRUCTURE; ACTIVE-SITE; HEMOPHILUS-INFLUENZAE; FLP RECOMBINATION; PROTEIN; IDENTIFICATION; BINDING; CHROMOSOME; CLEAVAGE AB HP1 integrase promotes site-specific recombination of the HP1 genome into that of Haemophilus influenzae. The isolated C-terminal domain (residues 165-337) of the protein interacts with the recombination site and contains the four catalytic residues conserved in the integrase family. This domain represents a novel fold consisting principally of well-packed cu helices, a surface beta sheet, and an ordered 17-residue C-terminal tail. The conserved triad of basic residues and the active-site tyrosine are contributed by a single monomer and occupy fixed positions in a defined active-site cleft. Dimers are formed by mutual interactions of the tail of one monomer with an adjacent monomer; this orients active-site clefts antiparallel to each other. C1 NIDDK,MOL BIOL LAB,NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT BIOCHEM,BALTIMORE,MD 21205. FU NCI NIH HHS [CA09110] NR 53 TC 114 Z9 116 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD APR 18 PY 1997 VL 89 IS 2 BP 227 EP 237 DI 10.1016/S0092-8674(00)80202-0 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WU888 UT WOS:A1997WU88800010 PM 9108478 ER PT J AU Glazner, GW Yadav, K Fitzgerald, S Coven, E Brenneman, DE Nelson, PG AF Glazner, GW Yadav, K Fitzgerald, S Coven, E Brenneman, DE Nelson, PG TI Cholinergic stimulation increases thrombin activity and gene expression in cultured mouse muscle SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE thrombin; acetyl choline; hirudin; cultured muscle; tetrodotoxin; gene expression; protease nexin I ID GROWTH FACTOR-II; PROTEASE-NEXIN-I; NEUROMUSCULAR-JUNCTION; SKELETAL-MUSCLE; SYNAPSE ELIMINATION; MESSENGER-RNA; POLYNEURONAL INNERVATION; NERVE REGENERATION; NEURITE OUTGROWTH; STRIATED-MUSCLE AB Activity-dependent synapse reduction is a major determinant of neuromuscular innervation. Previous research has shown that nanomolar concentrations of hirudin, a specific thrombin antagonist, significantly attenuates this reduction, and protease nexin 1 (PN1), an endogenous thrombin inhibitor closely localized to the neuromuscular synapse, can inhibit synapse reduction at similar concentrations. Protease inhibitors which do not inhibit thrombin, including cystatin and aprotinin, had no effect on synapse reduction. We present a series of experiments examining whether prothrombin and/or PN1 gene expression, as well as thrombin activity, are regulated in muscle cultures by acetylcholine (ACh) receptor activation. We also studied the effect of exogenous thrombin on synapse elimination in co-cultures of muscle and cholinergic neurons. Cultured muscle cells were electrically blocked with tetrodotoxin (TTX), or co-treated with ACh in order to isolate ACh receptor activation. Electrical blockade resulted in a decrease in thrombin release to about two-thirds of control values. The application of ACh to electrically blocked muscle cultures resulted in a 2.5-fold increase in thrombin activity released into the medium and a 2-fold increase in prothrombin gene expression. In contrast, ACh treatment in the presence of TTX had no effect on PN1 gene expression compared to treatment with TTX alone. In addition, exogenous thrombin significantly increased synapse elimination in unstimulated muscle/cholinergic neuron co-cultures. These results suggest that thrombin or a thrombin-like molecule released from muscle is required for activity-dependent synapse elimination and is regulated by neuromuscular activity. (C) 1997 Elsevier Science B.V. RP Glazner, GW (reprint author), NICHHD,DEV NEUROBIOL LAB,SECT DEV & MOL PHARMACOL,NIH,BLDG 49,ROOM 5A16,49 CONVENT DR MSC 4480,BETHESDA,MD 20892, USA. OI Yadav, Kabir/0000-0002-1092-9935 NR 40 TC 20 Z9 20 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 APR 18 PY 1997 VL 99 IS 2 BP 148 EP 154 DI 10.1016/S0165-3806(96)00213-1 PG 7 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA WT451 UT WOS:A1997WT45100003 ER PT J AU Gozes, I Davidson, A Gozes, Y Mascolo, R Barth, R Warren, D Hauser, J Brenneman, DE AF Gozes, I Davidson, A Gozes, Y Mascolo, R Barth, R Warren, D Hauser, J Brenneman, DE TI Antiserum to activity-dependent neurotrophic factor produces neuronal cell death in CNS cultures: Immunological and biological specificity SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE apoptosis; astroglia; vasoactive intestinal peptide; neurotrophic factor neurotrophin; cerebral cortex ID VASOACTIVE-INTESTINAL-PEPTIDE; SPINAL-CORD CULTURES; ELECTRICAL-ACTIVITY; ENVELOPE PROTEIN; SURVIVAL; EXPRESSION; INDUCTION; DAMAGE; CNTF; HIV AB Activity-dependent neurotrophic factor (ADNF) is a glia-derived protein that is neuroprotective at femtomolar concentrations. ADNF is released from astroglia after treatment with 0.1 nM vasoactive intestinal peptide (VIP). To further assess the biological role of ADNF, antiserum was produced following sequential injections of purified ADNF into mice. Anti-ADNF ascites fluid (1:10,000) decreased neuronal survival by 45-55% in comparison to untreated cultures or those treated with control ascites. The neuronal death after anti-ADNF treatment was observed in cultures derived from the spinal cord, hippocampus or cerebral cortex at similar IC50's. Using a terminal deoxynucleotidyl transferase in situ assay to estimate apoptosis in cerebral cortical cultures, anti-ADNF was shown to produce a 70% increase in the number of labeled cells in comparison to controls. In spinal cord cultures, anti-ADNF treatment produced a 20% decrease in choline acetyltransferase activity in comparison to controls. Neuronal cell death produced by the antiserum to ADNF was prevented in cultures co-treated with purified ADNF or ADNF-15, an active peptide derived from the parent ADNF. In vitro binding between the anti-ADNF and ADNF-15 was demonstrated with size exclusion chromatogaphy. Comparative studies with other growth factors (insulin-like growth factor-1, platelet-derived growth factor, nerve growth factor, epidermal growth factor, ciliary neurotrophic growth factor, and neurotrophin-3) demonstrated that only ADNF prevented neuronal cell death associated with electrical blockade. These investigations indicated that an ADNF-like substance was present in cultures derived from multiple locations in the central nervous system and that ADNF-15 exhibited both neuroprotection and immunogenicity. ADNF appears to be both a regulator of activity-dependent neuronal survival and a neuroprotectant. (C) 1997 Elsevier Science B.V. C1 NICHHD,SECT DEV & MOL PHARMACOL,LAB DEV PHARMACOL,NIH,BETHESDA,MD 20892. TEL AVIV UNIV,SACKLER SCH MED,DEPT CLIN BIOCHEM,IL-69978 TEL AVIV,ISRAEL. ISRAEL INST BIOL RES,NESS ZIONA,ISRAEL. RI Barth, Rolf/B-2542-2014 NR 41 TC 41 Z9 42 U1 0 U2 1 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 APR 18 PY 1997 VL 99 IS 2 BP 167 EP 175 DI 10.1016/S0165-3806(96)00215-5 PG 9 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA WT451 UT WOS:A1997WT45100005 ER PT J AU Sora, I Funada, M Uhl, GR AF Sora, I Funada, M Uhl, GR TI The mu-opioid receptor is necessary for [D-Pen(2),D-Pen(5)]enkephalin-induced analgesia SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE DPDPE ([D-Pen(2),D-Pen(5)]enkephalin); delta-opioid receptor; mu-opioid receptor knockout mouse ID AGONISTS AB Interactions between delta-opioid receptors and morphine preferring mu-opioid receptor subtypes have been suggested. Availability of transgenic mu-opioid receptor knockout mice allows assessment of mu-opioid receptor roles in the analgesia produced by the classical delta-opioid receptor agonist [D-Pen(2),D-Pen(5)]enkephalin (DPDPE) in hot-plate and tail-flick tests. DPDPE analgesia was dramatically reduced in mu-opioid receptor knockout mice in a gene-dose-dependent fashion. The analgesia induced by this classic delta-opioid receptor agonist depends on intact mu-opioid receptors, suggesting that selective delta-opioid receptor drugs may require mu-opioid receptor occupancies for full efficacy. C1 NIDA,MOL NEUROBIOL BRANCH,IRP,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. NR 8 TC 91 Z9 92 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD APR 18 PY 1997 VL 324 IS 2-3 BP R1 EP R2 DI 10.1016/S0014-2999(97)10016-4 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WV747 UT WOS:A1997WV74700025 PM 9145787 ER PT J AU Moore, KA Kunsman, GW Levine, BS Herman, MM Cervenak, J Hyde, TM AF Moore, KA Kunsman, GW Levine, BS Herman, MM Cervenak, J Hyde, TM TI A comparison of ethanol concentrations in the occipital lobe and cerebellum SO FORENSIC SCIENCE INTERNATIONAL LA English DT Article DE ethanol; postmortem distribution; regional brain concentrations ID POSTMORTEM AB While many publications have addressed the issue of ethanol concentration in brain tissue as a better indicator of impairment than blood alcohol concentration (BAG), very few have looked at the regional distribution of ethanol in the brain and its possible significance in postmortem sampling. This paper reports on the analysis of occipital pole and cerebellar hemisphere for ethanol in 25/brain samples obtained at autopsy from the brain collection of the National Institutes of Mental Health/Stanley Foundation. When available, these concentrations were compared to BAG. The average ratio of occipital lobe alcohol concentration (OAC) to BAC for cases which also had blood samples (18/24) was 0.9, SD=0.5, with a range of 0-1.8; the average ratio of cerebellar alcohol concentration (CAC) to BAC for these cases was 0.6, SD=0.4, range=0-1.2. When only those cases with a BAC greater than or equal to 0.04 g/dl (14/18 cases) were considered, the average OAC/BAC and CAC/BAC ratios were 0.8 (SD=0.4) and 0.7 (SD=0.4), respectively. These distribution ratios are well within the ranges reported by other authors and do nor significantly differ from each other. The cortical brain region available or selected for postmortem ethanol analysis is probably not critical. (C) 1997 Elsevier Science Ireland Ltd. C1 ARMED FORCES INST PATHOL,DIV FORENS TOXICOL,WASHINGTON,DC 20306. NIMH,CTR NEUROSCI,ST ELIZABETHS INTRAMURAL RES PROGRAM,NIH,WASHINGTON,DC 20032. NR 21 TC 6 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 0379-0738 J9 FORENSIC SCI INT JI Forensic Sci.Int. PD APR 18 PY 1997 VL 86 IS 1-2 BP 127 EP 134 DI 10.1016/S0379-0738(97)02129-4 PG 8 WC Medicine, Legal SC Legal Medicine GA WW937 UT WOS:A1997WW93700014 PM 9153789 ER PT J AU Yan, ZH Medvedev, A Hirose, T Gotoh, H Jetten, AM AF Yan, ZH Medvedev, A Hirose, T Gotoh, H Jetten, AM TI Characterization of the response element and DNA binding properties of the nuclear orphan receptor germ cell nuclear factor retinoid receptor-related testis-associated receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STEROIDOGENIC FACTOR-I; INVITRO TRANSCRIPTION; PROTAMINE-2 GENES; ACID RECEPTORS; MOUSE; SUPERFAMILY; PROTEIN; PROMOTER; MEMBER; HETERODIMERS AB Recently, we have reported the cloning of the germ cell-specific, nuclear orphan receptor germ cell nuclear factor (GCNF)/RTR. In this study, we characterize the RTR response elements by an electrophoretic mobility shift assay/polymerase chain reaction-based, DNA binding site selection strategy. RTR binds with the greatest affinity to response elements containing TCA(AG(G/T)TCA)(2) (consensus RTR response element; conRTRE), to which it binds as a homodimer. RTR is also able to bind as a monomer to a single core motif TCAAG(G/T)TCA, albeit with a lower affinity. Mutation analysis supports the specific requirements of the 5'-flanking sequence and the core motif of the RTRE for optimal binding of RTR. An RTR-specific antiserum (RTR-Ab2) was raised that causes supershift of the RTR-conRTRE complex in EMSA. Based on the sequence of the conRTRE, we located a putative RTRE, referred to as P2-RE, in the 5' promoter-flanking region of the mouse protamine 2 gene, which is induced during the same stage of spermatogenesis as RTR. The ability of RTR-Ab2 to cause a supershift of an RTR-RTRE complex with nuclear extracts from different tissues correlated with the tissue- and development-specific expression of RTR. Transfection of RTR in CV-1 cells was unable to cause RTRE-dependent transactivation of a CAT reporter gene; however, an RTR-VP16 fusion protein could induce transactivation through several RTREs, including PS-RE. C1 NIEHS,PULM PATHOBIOL LAB,CELL BIOL SECT,GAMETE BIOL SECT,NIH,RES TRIANGLE PK,NC 27709. NIEHS,REPROD & DEV TOXICOL LAB,NIH,RES TRIANGLE PK,NC 27709. OSAKA UNIV,SCH MED,DEPT MED 3,SUITA,OSAKA 565,JAPAN. RI Hirose, Takahisa /E-6117-2011; OI Jetten, Anton/0000-0003-0954-4445 NR 38 TC 69 Z9 69 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 APR 18 PY 1997 VL 272 IS 16 BP 10565 EP 10572 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WV262 UT WOS:A1997WV26200036 PM 9099702 ER PT J AU Taylor, GA Stauber, R Rulong, S Hudson, E Pei, V Pavlakis, GN Resau, JH VandeWoude, GF AF Taylor, GA Stauber, R Rulong, S Hudson, E Pei, V Pavlakis, GN Resau, JH VandeWoude, GF TI The inducibly expressed GTPase localizes to the endoplasmic reticulum, independently of GTP binding SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-NECROSIS-FACTOR; INTERFERON-GAMMA; IFN-GAMMA; MULTIPLE-SCLEROSIS; PROTEIN FAMILY; CELLS; RAS; ACTIVATION; RECEPTOR; SURVIVAL AB The inducibly expressed GTPase (IGTP) is representative of a newly identified group of interferon gamma-inducible GTPases, whose functions are currently unknown. We have begun to address the cellular function of IGTP by examining its subcellular distribution and its guanine nucleotide binding status. Using immunofluorescence, electron microscopy, and subcellular fractionation, IGTP was localized predominantly to the endoplasmic reticulum of both RAW 264.7 macrophages and C227 fibroblasts. In the immunostaining experiments, staining of discrete cytoplasmic structures on the periphery of the endoplasmic reticulum was also evident. Using polyethyleneimine-cellulose thin layer chromatography, the guanine nucleotides that complexed to immunoprecipitated IGTP, in both control and interferon gamma-stimulated cells, were 90-95% GTP and 5-10% GDP, suggesting that the protein was in an active state. A mutant IGTP protein was created that had no detectable complexed GTP, and in both subcellular fractionation and IGTP-green fluorescent protein fusion studies, this mutant also localized to the endoplasmic reticulum. These results suggested that the GTP binding status of IGTP is independent of its capacity to localize to the endoplasmic reticulum. Given these results, we propose that IGTP is representative of a new family of endoplasmic reticulum GTPases that may be involved in protein processing or trafficking. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. OI Stauber, Roland/0000-0002-1341-4523 NR 36 TC 66 Z9 68 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 APR 18 PY 1997 VL 272 IS 16 BP 10639 EP 10645 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WV262 UT WOS:A1997WV26200046 PM 9099712 ER PT J AU Pham, CTN Armstrong, RJ Zimonjic, DB Popescu, NC Payan, DG Ley, TJ AF Pham, CTN Armstrong, RJ Zimonjic, DB Popescu, NC Payan, DG Ley, TJ TI Molecular cloning, chromosomal localization, and expression of murine dipeptidyl peptidase I SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID REQUIRE GRANZYME-B; CATHEPSIN-C; SITU HYBRIDIZATION; CYTOTOXIC LYMPHOCYTES; RAPID INDUCTION; THIOL PROTEASE; GENE STRUCTURE; TARGET-CELLS; MOUSE; PURIFICATION AB Dipeptidyl peptidase I (DPPI) is a lysosomal cysteine protease that catalyzes the sequential removal of dipeptides from the amino termini of various protein substrates. We have isolated a cDNA coding for murine DPPI from mouse thymus and spleen cDNA libraries. The deduced amino acid sequence codes for a protein of 462 amino acid residues; comparison of this deduced sequence with that of rat and human DPPI revealed 90.1% and 77.8% identity, respectively. Using DPPI cDNA, we obtained two BAC (Bacterial Artificial Chromosome) clones that contained the murine DPPI locus. The DPPI gene consists of seven exons and 6 introns, and spans approximately 20 kilobases. Using fluorescence in situ chromosome hybridization, we localized murine DPPI to chromosome 7D3-E1.1. We determined that DPPI protein is widely distributed in mouse tissues, although its relative abundance varies from tissue to tissue. In contrast to previous reports, we show here that DPPI mRNA and protein levels and enzymatic activity are unchanged during in vitro T cell activation, implying that this enzyme is not rate-limiting for granzyme processing. C1 WASHINGTON UNIV,SCH MED,DEPT INTERNAL MED,DIV BONE MARROW TRANSPLANTAT & STEM CELL BIOL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT GENET,DIV BONE MARROW TRANSPLANTAT & STEM CELL BIOL,ST LOUIS,MO 63110. KHEPRI PHARMACEUT,S SAN FRANCISCO,CA 94080. UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT SURG,SAN FRANCISCO,CA 94143. NCI,EXPT CARCINOGENESIS LAB,MOL CYTOGENET SECT,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [CA49712]; NIDDK NIH HHS [DK49786]; NINDS NIH HHS [NS21710] NR 47 TC 48 Z9 49 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 APR 18 PY 1997 VL 272 IS 16 BP 10695 EP 10703 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WV262 UT WOS:A1997WV26200053 PM 9099719 ER PT J AU Minetti, CASA Tai, JY Blake, MS Pullen, JK Liang, SM Remeta, DP AF Minetti, CASA Tai, JY Blake, MS Pullen, JK Liang, SM Remeta, DP TI Structural and functional characterization of a recombinant PorB class 2 protein from Neisseria meningitidis - Conformational stability and porin activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OUTER-MEMBRANE PROTEINS; INFLUENZAE TYPE-B; ESCHERICHIA-COLI; ANGSTROM RESOLUTION; BACTERIAL PORIN; GONORRHOEAE; CHANNELS; IDENTIFICATION; DETERGENT; TYROSINE AB An outer membrane PorB class 2 protein from Neisseria meningitidis has been overexpresed in Escherichia coli, isolated from inclusion bodies, and refolded in the presence of zwitterionic detergent. The purified recombinant and native (strain M986) counterpart exhibit most of the typical functional and structural properties that are characteristic of bacterial porins. Channel forming activity has been monitored by incorporating class 2 into reconstituted liposomes and measuring the permeation rates of various oligosaccharides through the proteoliposomes to derive a pore diameter of similar to 1.6 nm, Structural studies employing a combination of spectroscopic and electrophoretic techniques reveal that recombinant and native class 2 are identical in terms of overall conformational stability, Both proteins form stable trimers in zwitterionic detergent and retain significant secondary and tertiary structure in the presence of SDS. The thermal unfolding of zwittergen-solubilized class 2 trimers (T-m = 88 degrees C) is reversible and characterized by solvent exposure of aromatic residues with concomitant disruption of tertiary and partial loss of secondary structures. SDS-induced destabilization and irreversible unfolding of the native trimeric assembly occurs at temperatures above 60 degrees C. Our physicochemical studies of PorB class 2 protein furnish significant insight regarding the structural and functional properties of this meningococcal outer membrane protein within the porin superfamily. C1 NHLBI,NIH,BETHESDA,MD 20892. RP Minetti, CASA (reprint author), N AMER VACCINE INC,12103 INDIAN CREEK CT,BELTSVILLE,MD 20705, USA. RI Minetti, Conceicao/B-5077-2009 OI Minetti, Conceicao/0000-0002-9682-2898 NR 48 TC 43 Z9 43 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 APR 18 PY 1997 VL 272 IS 16 BP 10710 EP 10720 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WV262 UT WOS:A1997WV26200055 PM 9099721 ER PT J AU Teramoto, H Salem, P Robbins, KC Bustelo, XR Gutkind, JS AF Teramoto, H Salem, P Robbins, KC Bustelo, XR Gutkind, JS TI Tyrosine phosphorylation of the vav proto-oncogene product links Fc epsilon RI to the Rac1-JNK pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL-TRANSDUCTION; KINASE; RECEPTOR; PROTEINS; ACTIVATION; DOMAIN; CELL; SYK; TCR AB Stimulation of high affinity IgE Fc receptors (Fc epsilon RI) in basophils and mast cells activates the tyrosine kinases Lyn and Syk and causes the tyrosine phosphorylation of phospholipase C-gamma resulting in the Ca2(+)- and protein kinase C-dependent secretion of inflammatory mediators. Concomitantly, Fc epsilon RI stimulation initiates a number of signaling events resulting in the activation of mitogen-activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK), which, in turn, regulate nuclear responses, including cytokine gene expression. To dissect the signaling pathway(s) linking Fc epsilon RI to MAPK and JNK, we reconstructed their respective biochemical routes by expression of a chimeric interleukin-2 receptor alpha subunit (Tac)-Fc epsilon RI gamma chain (Tac gamma) in COS-7 cells, Cross-linking of Tac gamma did not affect MAPK in COS-7 cells, but when coexpressed with the tyrosine kinase Syk, Tac gamma stimulation potently induced Syk and Shc tyrosine phosphorylation and MAPK activation. In contrast, Tac gamma did not signal JNK activation, even when coexpressed with Syk. Ectopic expression of a hematopoietic-specific guanine nucleotide exchange factor (GEF), Vav, reconstituted the Tac gamma-induced, Syk- and Rac1-dependent JNR activation; and tyrosine-phosphorylation of Vav by Syk stimulated its GEF activity for Rac1. Thus, these data strongly suggest that Vav plays a critical role linking Fc epsilon RI and Syk to the Rac1-JNK pathway. Furthermore, these findings define a novel signal transduction pathway involving a multimeric cell surface receptor acting on a cytosolic tyrosine kinase, which, in turn, phosphorylates a GEF, thereby regulating its activity toward a small GTP-binding protein and promoting the activation of a kinase cascade. C1 NIDR,NIH,MOL SIGNALING UNIT,ORAL & PHARYNGEAL CANC BRANCH,BETHESDA,MD 20892. SUNY STONY BROOK,SCH MED,DEPT PATHOL,STONY BROOK,NY 11794. SUNY STONY BROOK HOSP,STONY BROOK,NY 11794. RI Gutkind, J. Silvio/A-1053-2009 NR 24 TC 98 Z9 98 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 APR 18 PY 1997 VL 272 IS 16 BP 10751 EP 10755 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WV262 UT WOS:A1997WV26200060 PM 9099726 ER PT J AU Rani, CSS Wang, F Fuior, E Berger, A Wu, J Sturgill, TW BeitnerJohnson, D LeRoith, D Varticovski, L Spiegel, S AF Rani, CSS Wang, F Fuior, E Berger, A Wu, J Sturgill, TW BeitnerJohnson, D LeRoith, D Varticovski, L Spiegel, S TI Divergence in signal transduction pathways of platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) receptors - Involvement of sphingosine 1-phosphate in PDGF but not EGF signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE PATHWAY; SMOOTH-MUSCLE CELLS; CELLULAR PROLIFERATION; CRK PROTEIN; PC12 CELLS; PHOSPHATIDYLINOSITOL 3-KINASE; TYROSINE PHOSPHORYLATION; MITOGENIC SIGNAL; 3T3 FIBROBLASTS; 2ND MESSENGER AB Platelet-derived growth factor (PDGF) and serum, but not epidermal growth factor (EGF), stimulated sphingosine kinase activity in Swiss 3T3 fibroblasts and increased intracellular concentrations of sphingosine 1-phosphate (SPP), a sphingolipid second messenger (Olivera, A., and Spiegel, S. (1993) Nature 365, 557-560). We report herein that DL-threo-dihydrosphingosine (DHS), a competitive inhibitor of sphingosine kinase that prevents PDGF-induced SPP formation, specifically inhibited the activation of two cyclin-dependent kinases (p34(cdc2) kinase and Cdk2 kinase) induced by PDGF, but not by EGF. SPP reversed the inhibitory effects of DHS on PDGF-stimulated cyclin-dependent kinases and DNA synthesis, demonstrating that the DHS effects were mediated via inhibition of sphingosine kinase. DHS also markedly reduced PDGF-stimulated but not EGF-stimulated mitogen-activated protein kinase activity and DNA binding activity of activator protein-1. Examination of the early signaling events of PDGF action revealed that DHS did not affect PDGF-induced autophosphorylation of the growth factor receptor or phosphorylation of the SH2/SH3 adaptor protein She and its association with Grb2. This sphingosine kinase inhibitor did not abrogate activation of phosphatidylinositol 3-kinase by PDGF. In agreement, treatment with SPP had no effect on these responses but did, however, potently stimulate phosphorylation of Crk, another SH2/SH3 adaptor protein. Moreover, DHS inhibited PDGF-stimulated, but not EGF-stimulated, Crk phosphorylation. Thus, regulation of sphingosine kinase activity defines divergence in signal transduction pathways of PDGF and EGF receptors leading to mitogen-activated protein kinase activation. C1 GEORGETOWN UNIV,MED CTR,DEPT BIOCHEM & MOL BIOL,WASHINGTON,DC 20007. UNIV VIRGINIA,HLTH SCI CTR,HOWARD HUGHES MED INST,DEPT MED,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,HLTH SCI CTR,HOWARD HUGHES MED INST,DEPT PHARMACOL,CHARLOTTESVILLE,VA 22908. NIDDK,DIABET BRANCH,NIH,BETHESDA,MD 20892. TUFTS UNIV,SCH MED,DEPT MED & PHYSIOL,BOSTON,MA 02135. FU NCI NIH HHS [CA53094]; NIDDK NIH HHS [NIDK41077]; NIGMS NIH HHS [GM-43880] NR 58 TC 105 Z9 106 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 APR 18 PY 1997 VL 272 IS 16 BP 10777 EP 10783 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WV262 UT WOS:A1997WV26200064 PM 9099730 ER PT J AU Dumdei, EJ Blunt, JW Munro, MHG Pannell, LK AF Dumdei, EJ Blunt, JW Munro, MHG Pannell, LK TI Isolation of calyculins, calyculinamides, and swinholide H from the New Zealand deep-water marine sponge Lamellomorpha strongylata SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID THEONELLA-SWINHOEI; NATURAL-PRODUCTS; INHIBITORS; MACROLIDE; CONGENERS C1 UNIV CANTERBURY,DEPT CHEM,CHRISTCHURCH 1,NEW ZEALAND. NIDDK,ANALYT CHEM LAB,NIH,BETHESDA,MD 20892. OI Blunt, John/0000-0003-4053-4376 NR 14 TC 42 Z9 42 U1 1 U2 12 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 APR 18 PY 1997 VL 62 IS 8 BP 2636 EP 2639 DI 10.1021/jo961745j PG 4 WC Chemistry, Organic SC Chemistry GA WU860 UT WOS:A1997WU86000060 ER PT J AU Frazier, JA AlaghbandRad, J Jacobsen, L Lenane, MC Hamburger, S Albus, K Smith, A McKenna, K Rapoport, JL AF Frazier, JA AlaghbandRad, J Jacobsen, L Lenane, MC Hamburger, S Albus, K Smith, A McKenna, K Rapoport, JL TI Pubertal development and onset of psychosis in childhood onset schizophrenia SO PSYCHIATRY RESEARCH LA English DT Article DE psychotic symptoms; pubarche; menarche ID GENDER DIFFERENCES; LIFE EVENTS; PHENOMENOLOGY AB In this study, pubertal development was examined for a sample of children and adolescents with childhood onset schizophrenia (COS) defined as psychosis by age 12. Developmental and psychiatric histories were obtained for 28 adolescents (mean age 14.5 +/- 2.3 years) with severe, treatment refractory COS (14 males, 14 females). Age of onset of psychosis was also examined in relation to menarche and development of secondary sex characteristics. Girls had a trend towards developing secondary sex characteristics earlier than boys (P = 0.06), consistent with North American norms. Males (N = 14) and females (N = 14) had similar age of onset of psychosis. The age of development of secondary sex characteristics was associated with onset of psychosis for girls, but this finding was driven by one outlier. There was no significant correlation between development of psychosis and menarche. Neither male nor female probands differed significantly from their well siblings or from North American norms in their age of onset of pubertal development. There was no evidence of early onset of secondary sex characteristics for this sample. Finally, there was an absence of a clear relationship between onset of psychosis and indices of sexual development for these very early onset cases. (C) 1997 Elsevier Science Ireland Ltd. C1 NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892. UNIV DELAWARE,GRAD SCH CLIN PSYCHOL,NEWARK,DE. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL. RP Frazier, JA (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT,ACC 725,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 28 TC 21 Z9 21 U1 6 U2 8 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 APR 18 PY 1997 VL 70 IS 1 BP 1 EP 7 DI 10.1016/S0165-1781(97)03062-X PG 7 WC Psychiatry SC Psychiatry GA WZ834 UT WOS:A1997WZ83400001 PM 9172272 ER PT J AU Chandrasekharappa, SC Guru, SC Manickam, P Olufemi, SE Collins, FS EmmertBuck, MR Debelenko, LV Zhuang, ZP Lubensky, IA Liotta, LA Crabtree, JS Wang, YP Roe, BA Weisemann, J Boguski, MS Agarwal, SK Kester, MB Kim, YS Heppner, C Dong, QH Spiegel, AM Burns, AL Marx, SJ AF Chandrasekharappa, SC Guru, SC Manickam, P Olufemi, SE Collins, FS EmmertBuck, MR Debelenko, LV Zhuang, ZP Lubensky, IA Liotta, LA Crabtree, JS Wang, YP Roe, BA Weisemann, J Boguski, MS Agarwal, SK Kester, MB Kim, YS Heppner, C Dong, QH Spiegel, AM Burns, AL Marx, SJ TI Positional cloning of the gene for multiple endocrine neoplasia-type 1 SO SCIENCE LA English DT Article ID PROTEIN SEQUENCES; TUMORS; MUTATIONS; 11Q13 AB Multiple endocrine neoplasia-type 1 (MEN1) is an autosomal dominant familial cancer syndrome characterized by tumors in parathyroids, enteropancreatic endocrine tissues, and the anterior pituitary. DNA sequencing from a previously identified minimal interval on chromosome 11q13 identified several candidate genes, one of which contained 12 different frameshift, nonsense, missense, and in-frame deletion mutations in 14 probands from 15 families. The MEN1 gene contains 10 exons and encodes a ubiquitously expressed 2.8-kilobase transcript. The predicted 610-amino acid protein product, termed menin, exhibits no apparent similarities to any previously known proteins. The identification of MEN? will enable improved understanding of the mechanism of endocrine tumorigenesis and should facilitate early diagnosis. C1 NATL HUMAN GENOME RES INST,LAB GENE TRANSFER,NIH,BETHESDA,MD 20892. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. UNIV OKLAHOMA,DEPT CHEM & BIOCHEM,NORMAN,OK 73019. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,NIH,BETHESDA,MD 20894. NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892. RI Agarwal, Sunita/D-1428-2016 OI Agarwal, Sunita/0000-0002-7557-3191 NR 31 TC 1208 Z9 1234 U1 2 U2 21 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD APR 18 PY 1997 VL 276 IS 5311 BP 404 EP 407 DI 10.1126/science.276.5311.404 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WU477 UT WOS:A1997WU47700036 PM 9103196 ER PT J AU Ota, Y Samelson, LE AF Ota, Y Samelson, LE TI The product of the proto-oncogene c-cbl: A negative regulator of the Syk tyrosine kinase SO SCIENCE LA English DT Article ID FC-EPSILON-RI; SH3 DOMAIN; T-CELL; PROTOONCOGENE PRODUCT; EGF STIMULATION; JURKAT CELLS; V-CBL; RECEPTOR; PHOSPHORYLATION; ACTIVATION AB Engagement of antigen and immunoglobulin receptors on hematopoietic cells is directly coupled to activation of nonreceptor protein tyrosine kinases (PTKs) that then phosphorylate critical intracellular substrates. In mast cells stimulated through the Fc epsilon RI receptor, activation of several PTKs including Syk leads to degranulation and release of such mediators of the allergic response as histamine and serotonin. Regulation of Syk function occurred through interaction with the Cbl protein, itself a PTK substrate in this system. Overexpression of Cbl led to inhibition of Syk and suppression of serotonin release from mast cells, demonstrating its ability to inhibit a nonreceptor tyrosine kinase. Complex adaptor proteins such as Cbl can directly regulate the functions of the proteins they bind. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. NR 24 TC 222 Z9 224 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 APR 18 PY 1997 VL 276 IS 5311 BP 418 EP 420 DI 10.1126/science.276.5311.418 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WU477 UT WOS:A1997WU47700041 PM 9103201 ER PT J AU Platt, FM Neises, GR Reinkensmeier, G Townsend, MJ Perry, VH Proia, RL Winchester, B Dwek, RA Butters, TD AF Platt, FM Neises, GR Reinkensmeier, G Townsend, MJ Perry, VH Proia, RL Winchester, B Dwek, RA Butters, TD TI Prevention of lysosomal storage in Tay-Sachs mice treated with N-butyldeoxynojirimycin SO SCIENCE LA English DT Article ID GLYCOLIPID BIOSYNTHESIS; REPLACEMENT THERAPY; TARGETED DISRUPTION; GAUCHER DISEASE; HEXA GENE AB The glycosphingolipid (GSL) lysosomal storage diseases result from the inheritance of defects in the genes encoding the enzymes required for catabolism of GSLs within lysosomes. A strategy for the treatment of these diseases, based on an inhibitor of GSL biosynthesis N-butyldeoxynojirimycin, was evaluated in a mouse model of Tay-Sachs disease. When Tay-Sachs mice were treated with N-butyldeoxynojirimycin, the accumulation of G(M2) in the brain was prevented, with the number of storage neurons and the quantity of ganglioside stored per cell markedly reduced. Thus, limiting the biosynthesis of the substrate (G(M2)) for the defective enzyme (beta-hexosaminidase A) prevents GSL accumulation and the neuropathology associated with its lysosomal storage. C1 MONSANTO CO,ST LOUIS,MO 63198. UNIV OXFORD,DEPT PHARMACOL,OXFORD OX1 3QT,ENGLAND. NIDDKD,NIH,BETHESDA,MD 20892. INST CHILD HLTH,LONDON WC1N 1EH,ENGLAND. RP Platt, FM (reprint author), UNIV OXFORD,GLYCOBIOL INST,DEPT BIOCHEM,S PARKS RD,OXFORD OX1 3QU,ENGLAND. RI Platt, Frances/G-1004-2010; Proia, Richard/A-7908-2012 NR 14 TC 277 Z9 282 U1 2 U2 14 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD APR 18 PY 1997 VL 276 IS 5311 BP 428 EP 431 DI 10.1126/science.276.5311.428 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WU477 UT WOS:A1997WU47700044 PM 9103204 ER PT J AU Tasaki, I AF Tasaki, I TI Rapid volume expansion in the Torpedo electric organ associated with its postsynaptic potential SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ACETYLCHOLINE AB By electrically stimulating Torpedo electric organs enclosed in a sealed plastic chamber, it was demonstrated that the production of a postsynaptic potential is accompanied by a rapid increase in the volume of the organ. This increase started almost simultaneously with the onset of the postsynaptic potential and reached its maximum at about the end of the potential. The volume returned slowly to its resting level. Repetitive stimulation produced a summation of volume changes. The maximum change evoked by a single electric shock was roughly 10(-6) times the electrocyte volume. The thermal expansion of the organ associated with the production of a postsynaptic potential accounts for roughly 25% or less of this volume increase. The possibility is pointed out that a cation-exchange process involving Ca2+ on anionic sites in the electrocyte protoplasm may be at the base of the volume changes. (C) 1997 Academic Press. RP Tasaki, I (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 15 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 17 PY 1997 VL 233 IS 2 BP 305 EP 308 DI 10.1006/bbrc.1997.6451 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WW748 UT WOS:A1997WW74800003 PM 9144529 ER PT J AU Hummer, G Pratt, LR Garcia, AE Berne, BJ Rick, SW AF Hummer, G Pratt, LR Garcia, AE Berne, BJ Rick, SW TI Electrostatic potentials and free energies of solvation of polar and charged molecules SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Letter ID PERIODIC BOUNDARY-CONDITIONS; WATER; SIMULATIONS; HYDRATION; DYNAMICS AB Theories of solvation free energies often involve electrostatic potentials at the position of a solute charge. Simulation calculations that apply cutoffs and periodic boundary conditions based on molecular centers result in center-dependent contributions to electrostatic energies due to a systematic sorting of charges in radial shells. This sorting of charges induces a surface-charge density at the cutoff sphere or simulation-box boundary that depends on the choice of molecular centers. We identify a simple solution that gives correct, center-independent results, namely the radial integration of charge densities. Our conclusions are illustrated for a Lennard-Jones solute in water. The present results can affect the parametrization of force fields. C1 COLUMBIA UNIV,DEPT CHEM,NEW YORK,NY 10027. COLUMBIA UNIV,CTR BIOMOL SIMULAT,NEW YORK,NY 10027. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. RP Hummer, G (reprint author), LOS ALAMOS NATL LAB,DIV THEORET,MS K710,LOS ALAMOS,NM 87545, USA. RI Pratt, Lawrence/H-7955-2012; Hummer, Gerhard/A-2546-2013 OI Pratt, Lawrence/0000-0003-2351-7451; Hummer, Gerhard/0000-0001-7768-746X NR 15 TC 91 Z9 93 U1 0 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1089-5647 J9 J PHYS CHEM B JI J. Phys. Chem. B PD APR 17 PY 1997 VL 101 IS 16 BP 3017 EP 3020 DI 10.1021/jp964037a PG 4 WC Chemistry, Physical SC Chemistry GA WU630 UT WOS:A1997WU63000002 ER PT J AU Appel, LJ Moore, TJ Obarzanek, E Vollmer, WM Svetkey, LP Sacks, FM Bray, GA Vogt, TM Cutler, JA Windhauser, MM Lin, PH Karanja, N AF Appel, LJ Moore, TJ Obarzanek, E Vollmer, WM Svetkey, LP Sacks, FM Bray, GA Vogt, TM Cutler, JA Windhauser, MM Lin, PH Karanja, N TI A clinical trial of the effects of dietary patterns on blood pressure SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 69th Scientific-Session of the American-Heart-Assoc iation CY NOV 13, 1996 CL NEW ORLEANS, LA SP Amer Heart Assoc ID NUTRITION EXAMINATION SURVEY; MILD HYPERTENSION; NATIONAL-HEALTH; VEGETARIAN DIET; POPULATION AB Background It is known that obesity, sodium intake, and alcohol consumption influence blood pressure. In this clinical trial, Dietary Approaches to Stop Hypertension, we assessed the effects of dietary patterns on blood pressure. Methods We enrolled 459 adults with systolic blood pressures of less than 160 mm Hg and diastolic blood pressures of 80 to 95 mm Hg. For three weeks, the subjects were fed a control diet that was low in fruits, vegetables, and dairy products, with a fat content typical of the average diet in the United States. They were then randomly assigned to receive for eight weeks the control diet, a diet rich in fruits and vegetables, or a ''combination'' diet rich in fruits, vegetables, and low-fat dairy products and with reduced saturated and total fat. Sodium intake and body weight were maintained at constant levels. Results At base line, the mean (+/-SD) systolic and diastolic blood pressures were 131.3+/-10.8 mm Hg and 84.+/-4.7 mm Hg, respectively. The combination diet reduced systolic and diastolic blood pressure by 5.5 and 3.0 mm Hg more, respectively, than the control diet (P<0.001 for each); the fruits-and-vegetables diet reduced systolic blood pressure by 2.8 mm Hg more (P<0.001) and diastolic blood pressure by 1.1 mm Hg more (P=0.07) than the control diet. Among the 133 subjects with hypertension (systolic pressure, greater than or equal to 140 mm Hg; diastolic pressure, greater than or equal to 90 mm Hg; or both), the combination diet reduced systolic and diastolic blood pressure by 11.4 and 5.5 mm Hg more, respectively, than the control diet (P<0.001 for each); among the 326 subjects without hypertension, the corresponding reductions were 3.5 mm Hg (P<0.001) and 2.1 mm Hg (P=0.003). Conclusions A diet rich in fruits, vegetables, and low-fat dairy foods and with reduced saturated and total fat can substantially lower blood pressure. This diet offers an additional nutritional approach to preventing and treating hypertension. (C) 1997, Massachusetts Medical Society. C1 KAISER PERMANENTE CTR HLTH RES,PORTLAND,OR 97227. JOHNS HOPKINS UNIV,WELCH CTR PREVENT EPIDEMIOL & CLIN RES,BALTIMORE,MD. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. MERCK & CO INC,WESTWOOD,MA. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DUKE HYPERTENS CTR,DURHAM,NC. DUKE UNIV,MED CTR,SARAH W STEDMAN CTR NUTR STUDIES,DURHAM,NC. HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,BOSTON,MA 02115. PENNINGTON BIOMED RES CTR,BATON ROUGE,LA 70808. FU NHLBI NIH HHS [HL50968, HL50972, HL50981] NR 30 TC 2451 Z9 2517 U1 14 U2 203 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 APR 17 PY 1997 VL 336 IS 16 BP 1117 EP 1124 DI 10.1056/NEJM199704173361601 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA WU003 UT WOS:A1997WU00300001 PM 9099655 ER PT J AU Campos, SM Walden, T AF Campos, SM Walden, T TI Images in clinical medicine - Spigelian hernia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article C1 NCI,BETHESDA,MD 20892. RP Campos, SM (reprint author), BRIGHAM & WOMENS HOSP,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 17 PY 1997 VL 336 IS 16 BP 1149 EP 1149 DI 10.1056/NEJM199704173361605 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA WU003 UT WOS:A1997WU00300005 PM 9099659 ER PT J AU Krown, SE Rabkin, CS AF Krown, SE Rabkin, CS TI Intralesional human chorionic gonadotropin for Kaposi's sarcoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NCI,BETHESDA,MD 20892. RP Krown, SE (reprint author), MEM SLOAN KETTERING CANC CTR,1275 YORK AVE,NEW YORK,NY 10021, USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 17 PY 1997 VL 336 IS 16 BP 1188 EP 1189 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA WU003 UT WOS:A1997WU00300031 ER PT J AU Sheikh, MS Chen, YQ Smith, ML Fornace, AJ AF Sheikh, MS Chen, YQ Smith, ML Fornace, AJ TI Role of p21(Waf1/Cip1/Sd1) in cell death and DNA repair as studied using a tetracycline-inducible system in p53-deficient cells SO ONCOGENE LA English DT Article DE excision repair; cell death; adriamycin; uv-irradiation; p53 deficient cells ID NUCLEOTIDE EXCISION-REPAIR; P53-MEDIATED G(1) ARREST; CYCLIN-DEPENDENT KINASES; HUMAN BREAST-CARCINOMA; TUMOR SUPPRESSION; GENE-EXPRESSION; GROWTH ARREST; CANCER-CELLS; P21; INDUCTION AB Postulated roles for p21(Waf1/Cip1/Sdi1) (p21) in DNA repair and apoptosis remain controversial. Studies suggest both stimulatory and inhibitory effects of p21 in DNA repair. p21 has also been implicated in induction or protection from apoptosis. Using the tetracycline inducible expression system, we studied the role of p21 in DNA repair and apoptosis in wild-type p53 deficient DLD1 colorectal carcinoma cells. These cells displayed marked heterogeneity in their ability to tolerate higher levels of exogenous p21, The majority of the p21 overexpressing cells grew slower and did not exhibit apoptotic phenotype, some cells underwent apoptotic death within 5-8 days following p21 induction while other became giant cells prior to undergoing cell death. Induction of p21 transgene neither sensitized to nor protected from adriamycin-induced acute cell death. p21 also did not alter the clonogenic survival following adriamycin treatment. Clonogenic survival u.v.-irradiation was, however, increased when p21 expression was transiently induced a few hours before and after u.v.-irradiation. Consistent with its effect on clonogenic survival, p21 also enhanced the cellular capacity to repair three different exogenously introduced u.v.-damaged reporter plasmids. Taken together our results demonstrate that p21 may modulate the nucleotide excision repair process to facilitate the repair of u.v.-type DNA damage even in the absence of wild-type p53. C1 WAYNE STATE UNIV, SCH MED, DEPT PATHOL, DETROIT, MI 48201 USA. RP Sheikh, MS (reprint author), NCI, MOL PHARMACOL LAB, NIH, BETHESDA, MD 20892 USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 42 TC 106 Z9 113 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 17 PY 1997 VL 14 IS 15 BP 1875 EP 1882 DI 10.1038/sj.onc.1201004 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA WW166 UT WOS:A1997WW16600014 PM 9150394 ER PT J AU Yanovski, S AF Yanovski, S TI Pharmacotherapy in the management of obesity - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP Yanovski, S (reprint author), NIDDKD,BETHESDA,MD 20892, USA. NR 2 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 APR 16 PY 1997 VL 277 IS 15 BP 1202 EP 1202 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA WT403 UT WOS:A1997WT40300025 ER PT J AU Peters, R Sikorski, R AF Peters, R Sikorski, R TI Digital dialogue - Sharing information and interests on the Internet SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article C1 HARVARD UNIV,SCH MED,BOSTON,MA. NATL CANC INST,BETHESDA,MD. RP Peters, R (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,WANG BLDG,ACC-1,FRUIT ST,BOSTON,MA 02114, USA. NR 8 TC 24 Z9 24 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 16 PY 1997 VL 277 IS 15 BP 1258 EP 1260 DI 10.1001/jama.277.15.1258 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA WT403 UT WOS:A1997WT40300045 PM 9103353 ER PT J AU Manne, U Myers, RB Srivastava, S Grizzle, WE AF Manne, U Myers, RB Srivastava, S Grizzle, WE TI Loss of tumor marker-immunostaining intensity on stored paraffin slides of breast cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID P53 ANTIGEN LOSS C1 UNIV ALABAMA,DEPT PATHOL,BIRMINGHAM,AL 35294. NCI,EARLY DETECT RES NETWORK,BETHESDA,MD 20892. RI Manne, Upender/D-5613-2009 NR 9 TC 25 Z9 26 U1 1 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 16 PY 1997 VL 89 IS 8 BP 585 EP 586 DI 10.1093/jnci/89.8.585 PG 2 WC Oncology SC Oncology GA WU268 UT WOS:A1997WU26800019 PM 9106651 ER PT J AU Weed, DL Kramer, BS AF Weed, DL Kramer, BS TI Induced abortion and risk for breast cancer: Reporting (recall) bias in a Dutch case-control study - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 GEORGETOWN UNIV,KENNEDY INST ETH,WASHINGTON,DC 20057. RP Weed, DL (reprint author), NCI,DIV CANC PREVENT & CONTROL,NIH,EXECUT PLAZA S,RM T-41,BETHESDA,MD 20892, USA. NR 5 TC 0 Z9 0 U1 1 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 16 PY 1997 VL 89 IS 8 BP 589 EP 589 PG 1 WC Oncology SC Oncology GA WU268 UT WOS:A1997WU26800022 ER PT J AU Czajkowski, SM Terrin, M Lindquist, R Hoogwerf, B Dupuis, G Shumaker, SA Gray, JR Herd, JA TreatJacobson, D Zyzanski, S Knatterud, GL AF Czajkowski, SM Terrin, M Lindquist, R Hoogwerf, B Dupuis, G Shumaker, SA Gray, JR Herd, JA TreatJacobson, D Zyzanski, S Knatterud, GL TI Comparison of preoperative characteristics of men and women undergoing coronary artery bypass grafting (the POST coronary artery bypass graft [CABG] Biobehavioral Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID SEX-DIFFERENCES; ECONOMIC-RESOURCES; CARDIAC-SURGERY; FEMALE-PATIENTS; DISEASE; DEPRESSION; MORTALITY; BIAS; RACE AB A cohort of 759 coronary artery bypass grafting (CABG) patients (269 women and 490 men) was enrolled in the prospective POST CABG Biobehavioral Study at 5 clinical centers in the United States and Canada. Sociodemographic and medical data were obtained by interview and from medical charts. Health-related quality of life and psychosocial data were ascertained preoperatively by interview and questionnaire for those patients whose condition allowed preoperative assessment and was compared among patients from hospitals enrolling both male and female patients (143 women and 267 men). Women enrolled in the Biobehavioral Study were older than men (65.4 +/- 9.0 vs 61.8 +/- 9.7 years, p < 0.001) and more likely to have a preoperative medical condition which precluded biobehavioral evaluation (47% vs 34%, p < 0.001). Women were less likely to be high school graduates (59% vs 74%, p < 0.001), were less likely to be earning greater than or equal to$25,000 per year (39% vs 69%, p < 0.001), and were married less often at the time of surgery (59% vs 85%, p < 0.001). Fewer women than men were able to perform basic self-care activities (p < 0.001) and social activities (p < 0.001). Women were also less able to perform the more demanding activities required for independent living, recreation, and maintaining a household (p < 0.001). Women were also more anxious (p = 0.01) and reported more depressive symptoms (p < 0.001) than men. These data suggest that plans for perioperative and convalescent care for women undergoing CABG should take into account their less favorable medical and psychosocial status relative to men. (C) 1997 by Excerpta Medica, Inc. C1 NHLBI,BETHESDA,MD 20892. MARYLAND MED RES INST,BALTIMORE,MD. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. CLEVELAND CLIN FDN,CLEVELAND,OH 44195. MONTREAL HEART INST,MONTREAL,PQ H1T 1C8,CANADA. CEDARS SINAI MED CTR,LOS ANGELES,CA 90048. BAYLOR COLL MED,HOUSTON,TX 77030. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. FU NHLBI NIH HHS [N01-HC-75072, N01-HC-75071, N01-HC-75073] NR 30 TC 62 Z9 64 U1 1 U2 2 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 APR 15 PY 1997 VL 79 IS 8 BP 1017 EP 1024 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WV114 UT WOS:A1997WV11400003 PM 9114757 ER PT J AU Hyland, A Cummings, KM Lynn, WR Corle, D Giffen, CA AF Hyland, A Cummings, KM Lynn, WR Corle, D Giffen, CA TI Effect of proxy-reported smoking status on population estimates of smoking prevalence SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE data collection; prevalence; smoking ID VALIDITY; SELF; RESPONDENTS; INFORMATION; VALIDATION; MORTALITY AB The use of proxy respondents in surveys designed to provide population estimates of smoking prevalence offers an inexpensive way to obtain these data. The accuracy of this information is examined in analyzing data from tobacco use surveys of adults conducted in 22 North American communities as part of the National Cancer Institute's Community intervention Trial for Smoking Cessation. Proxy-reported smoking status was obtained in a cross-sectional telephone survey conducted from August 1993 to January 1994 (n = 99,682). Self-reported smoking status was obtained from an in-depth interview of a sample of the respondents aged 25-64 years enumerated from the telephone survey (n = 31,417). Discrepancy rates were calculated by comparing the proxy-reported and self-reported smoking statuses of a given individual (n = 10,226), in both surveys, respondents were categorized as current smokers (those who currently smoke and have smoked at least 100 cigarettes in their lifetime), recent quitters (less than or equal to 8 years since cessation), long-term quitters (>8 years since cessation), and never smokers. The overall discrepancy rate between the self-report and the proxy report was 5.4%. Self-respondents who were black, Hispanic, Asian, recent quitters, or aged 25-34 years were more likely to have inconsistent proxy reports, The authors estimate that the screener interview underestimated the true smoking prevalence by 0.1% when they corrected for smoking status discrepancies. These results confirm that proxy-reported smoking status is an accurate and effective means to monitor populationwide smoking prevalence of adults. C1 ROSWELL PK CANC INST,DEPT CANC CONTROL & EPIDEMIOL,BUFFALO,NY 14263. NCI,CANC CONTROL RES PROGRAM,DIV CANC PREVENT & CONTROL,NIH,BETHESDA,MD 20892. NCI,BIOMETRY BRANCH,DIV CANC PREVENT & CONTROL,NIH,BETHESDA,MD 20892. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. NR 17 TC 36 Z9 36 U1 0 U2 2 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 15 PY 1997 VL 145 IS 8 BP 746 EP 751 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WU604 UT WOS:A1997WU60400009 PM 9126001 ER PT J AU Dracup, K Alonzo, AA Atkins, JM Bennett, NM Braslow, A Clark, LT Eisenberg, M Ferdinand, KC Frye, R Green, L Hill, MN Kennedy, JW KlineRogers, E Moser, DK Ornato, JP Pitt, B Scott, JD Selker, HP Silva, SJ Thies, W Weaver, WD Wenger, NK White, SK AF Dracup, K Alonzo, AA Atkins, JM Bennett, NM Braslow, A Clark, LT Eisenberg, M Ferdinand, KC Frye, R Green, L Hill, MN Kennedy, JW KlineRogers, E Moser, DK Ornato, JP Pitt, B Scott, JD Selker, HP Silva, SJ Thies, W Weaver, WD Wenger, NK White, SK TI The physician's role in minimizing prehospital delay in patients at high risk for acute myocardial infarction: Recommendations from the National Heart Attack Alert Program SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID ACUTE CHEST PAIN; PRE-HOSPITAL PHASE; THROMBOLYTIC THERAPY; CORONARY ANGIOPLASTY; DISEASE; EMERGENCY; SYMPTOMS; ARRIVAL; TIME; INTERVENTION AB Physicians and other health care professionals play an important role in reducing the delay to treatment in patients who have an evolving acute myocardial infarction. A multidisciplinary working group has been convened by the National Heart Attack Alert Program (which is coordinated by the National Heart, Lung, and Blood Institute of the National Institutes of Health) to address this concern. The working group's recommendations target specific groups of patients: those who are known to have coronary heart disease, atherosclerotic disease of the aorta or peripheral arteries, or cerebrovascular disease. The risk for acute myocardial infarction or death in such patients is five to seven times greater than that in the general population. The working group recommends that these high-risk patients be clearly informed about symptoms that they mig ht have during a coronary occlusion, steps that they should take, the importance of contacting emergency medical services, the need to report to an appropriate facility quickly, treatment options that are available if they present early, and rewards of early treatment in terms of improved quality of life. These instructions should be reviewed frequently and reinforced with appropriate written material, and patients should be encouraged to have a plan and to rehearse it periodically. Because of the important role of the bystander in increasing or decreasing delay to treatment, family members and significant others should be included in all instruction. Finally, physicians' offices and clinics should devise systems to quickly assess patients who telephone or present with symptoms of a possible acute myocardial infarction. C1 NHLBI,NATL HEART ATTACK ALERT PROGRAM,NIH,BETHESDA,MD 20892. NR 61 TC 122 Z9 124 U1 3 U2 5 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 APR 15 PY 1997 VL 126 IS 8 BP 645 EP 651 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA WT580 UT WOS:A1997WT58000012 PM 9103133 ER PT J AU Rossak, M Schafer, A Xu, NX Gage, DA Benning, C AF Rossak, M Schafer, A Xu, NX Gage, DA Benning, C TI Accumulation of sulfoquinovosyl-1-O-dihydroxyacetone in a sulfolipid-deficient mutant of Rhodobacter sphaeroides inactivated in sqdC SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE glycolipid; glycosyl transferase; MALDI mass spectrometry; gene inactivation; photosynthetic bacterium ID UDP-SULFOQUINOVOSE; MASS-SPECTROMETRY; DIACYLGLYCEROL; IDENTIFICATION; BIOSYNTHESIS; SPECTRA; MS AB The biosynthesis of the sulfolipid sulfoquinovosyl diacylglycerol in the purple bacterium Rhodobacter sphaeroides requires at least four genes: sqdA, sqdB, sqdC, and sqdD. As part of our strategy aimed at the elucidation of the function of the different sqd gene products, we insertionally inactivated sqdC of R. sphaeroides. The resulting sqdC null mutant showed only a 90% reduction in sulfolipid content. Apparently, the sqdC gene product is required for optimal sulfolipid biosynthesis, but either catalyzes no essential reaction in the pathway or can be functionally replaced to a certain extent by a different protein. The mutant accumulated a S-35-labeled compound that was purified to homogeneity from cell extracts. Matrix-assisted laser desorption mass spectrometry and nuclear magnetic resonance spectroscopy provided conclusive structural evidence to identify the compound as alpha-D-sulfoquinovosyl-1-O-dihydroxyacetone that exists in two interconvertible, keto and hemiacetal forms. Incubation of wild-type protein extracts with the labeled compound did not result in the incorporation into sulfolipid as would be expected for an intermediate of the pathway. Based on our results we propose that the sqdC gene product mediates the substrate specificity of the UDP-sulfoquinovose:diacylglycerol sulfoquinovosyltransferase that is encoded by sqdD and that catalyzes the final reaction of sulfolipid biosynthesis. (C) 1997 Academic Press. C1 IGF BERLIN GMBH IL,D-14195 BERLIN,GERMANY. FREE UNIV BERLIN,INST ORGAN CHEM,D-14195 BERLIN,GERMANY. MICHIGAN STATE UNIV,DEPT BIOCHEM,NIH,MASS SPECTROMETRY FACIL,E LANSING,MI 48824. NR 25 TC 38 Z9 40 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 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD APR 15 PY 1997 VL 340 IS 2 BP 219 EP 230 DI 10.1006/abbi.1997.9931 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA WV118 UT WOS:A1997WV11800009 PM 9143325 ER PT J AU Oh, CK Neurath, M Cho, JJ Semere, T Metcalfe, DD AF Oh, CK Neurath, M Cho, JJ Semere, T Metcalfe, DD TI Two different negative regulatory elements control the transcription of T-cell activation gene 3 in activated mast cells SO BIOCHEMICAL JOURNAL LA English DT Article ID ENHANCER ELEMENTS; SILENCER ELEMENT; BETA-CHEMOKINE; EXPRESSION; PROMOTER; TCA3; DNA; SEQUENCE; PROTEIN; CHICKEN AB T-cell activation gene 3 (TCA3) encodes a beta-chemokine that is transcriptionally regulated in mast cells; the gene has a functional NF-kappa B element at positions -194 to -185. The 5'-flanking region of this gene is also known to have a negative regulatory region between -2057 and -1342. To characterize the negative regulatory elements (NREs), this region was sequenced and then digested by HindIII enzyme into two fragments, NRE-1 (-2057 to -1493) and NRE-2 (-1492 to -1342). Both NRE-1 and NRE-2 in the 5'-3' orientation inhibited chloramphenicol acetyltransferase (CAT)-protein synthesis by a TCA3-CAT construct transfected into mast cells that were then activated. Only NRE-1 inhibited CAT-protein syn thesis in the 3'-5' orientation. Further deletion of the 5' region of NRE-1 partially abolished the inhibitory activity. Both NRE-1 and NRE-2 inhibited the activity of a CD20-CAT construct independent of cell activation. Electrophoretic mobility shift assays showed DNA-protein complex formation with subsequences (CCCCCATTCT) of NRE-1 (NRE-1a) and (CCATGA) of NRE-2 (NRE-2b). NRE-1a appears to be novel. NRE-2b is identical with a putative silencer motif in the alpha(IIb) integrin gene. Site-directed mutagenesis demonstrated that both NRE-1a and NRE-2b are important in the negative regulation of TCA3 promoter activity. In vivo ligation-mediated PCR foot printing of the NRE-2 region revealed protection between -1372 and -1354, which contains NRE-2b. The data thus demonstrate identity of a silencer motif, here termed NRE-2b, in both the alpha(IIb), integrin gene and the TCA3, and that this silencer region in mast cells is functional both in vivo and in vitro. Further, evidence is presented that the promoter for TCA3 contains a novel silencer motif, termed NRE-1a, characterized by a CT-rich sequence. C1 NIAID,ALLERG DIS LAB,NIH,BETHESDA,MD 20892. HARBOR UCLA MED CTR,DEPT PEDIAT,TORRANCE,CA 90509. NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,NIH,BETHESDA,MD 20892. NR 40 TC 9 Z9 9 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD APR 15 PY 1997 VL 323 BP 511 EP 519 PN 2 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WV762 UT WOS:A1997WV76200029 PM 9163346 ER PT J AU Garrett, DS Seok, YJ Peterkofsky, A Clore, GM Gronenborn, AM AF Garrett, DS Seok, YJ Peterkofsky, A Clore, GM Gronenborn, AM TI Identification by NMR of the binding surface for the histidine-containing phosphocarrier protein HPr on the N-terminal domain of enzyme I of the Escherichia coli phosphotransferase system SO BIOCHEMISTRY LA English DT Article ID RESTRAINED MOLECULAR-DYNAMICS; HIGH-RESOLUTION STRUCTURE; BACILLUS-SUBTILIS; ACTIVE-SITE; SALMONELLA-TYPHIMURIUM; TERTIARY STRUCTURE; GLUCOSE PERMEASE; SUGAR-TRANSPORT; IIA-DOMAIN; SPECTROSCOPY AB The interaction between the similar to 30 kDa N-terminal domain of enzyme I (EIN) and the similar to 9.5 kDa histidine-containing phosphocarrier protein HPr of the Escherichia coli phosphoenolpyruvate:sugar phosphotransferase system has been investigated by heteronuclear magnetic resonance spectroscopy. The complex is in fast exchange, permitting us to follow the chemical shift changes of the backbone NH and N-15 resonances of EIN upon complex; formation by recording a series of H-1-N-15 correlation spectra of uniformly N-15-labeled EIN in the presence of increasing amounts of HPr at natural isotopic abundance. The equilibrium association constant derived from analysis of the titration data is similar to 1.5 x 10(5) M-1, and the lower limit for the dissociation rate constant is 1100 s(-1). By mapping the backbone chemical shift perturbations on the three-dimensional solution structure of EIN [Garrett, D. S., Seek, Y.-J., Liao, D.-I., Peterkofsky, A., Gronenborn, A. M., & Clore, G. M. (1997) Biochemistry 36, 2517-2530], we have identified the binding surface of EIN in contact with HPr. This surface is primarily located in the ct domain and involves helices H1, H2, and H4, as well as the hinge region connecting helices H2 and H2'. The data also indicate that the active site His 15 of HPr must approach the active site His 189 of EIN along the shallow depression at the interface of the cr and alpha/beta domains. Interestingly, both the backbone and side chain resonances (assigned from a long-range H-1-N-15 correlation spectrum) of His 189, which is located at the N-terminus of helix H6 in he alpha/beta domain, are only minimally perturbed upon complexation, indicating that His 189 (in the absence of phosphorylation) does not undergo any significant conformational change or change in pK(a) value upon HPr binding. On the basis of results of this study, as well as a previous study which delineated the interaction surface for EI on HPr [van Nuland, N. A. J., Boelens, R., Scheek, R. M., & Robillard, G. T. (1995) J. Mol. Biol. 246, 180-193], a model for the EIN/HPr complex is proposed in which helix 1 (residues 16-27) and the helical loop (residues 49-53) of HPr slip between the two pairs of helices constituting the ct domain of EIN. In addition, we suggest a functional role for the kink between helices H2 and H2' of EIN, providing a flexible joint for this interaction to take place. C1 NIDDKD,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. NHLBI,BIOCHEM GENET LAB,NIH,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 34 TC 182 Z9 183 U1 1 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 15 PY 1997 VL 36 IS 15 BP 4393 EP 4398 DI 10.1021/bi970221q PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WU189 UT WOS:A1997WU18900004 PM 9109646 ER PT J AU Holte, LL Gawrisch, K AF Holte, LL Gawrisch, K TI Determining ethanol distribution in phospholipid multilayers with MAS-NOESY spectra SO BIOCHEMISTRY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; MODEL MEMBRANES; SPECTROSCOPY; WATER; HYDRATION; BILAYERS; LECITHIN; VESICLES; BRAIN; GANGLIOSIDES AB The location of an ethanol molecule within a membrane, an issue of considerable controversy, was investigated directly by NMR with two-dimensional NOESY. Lipid and ethanol H-1 NMR resonances of multilamellar liposomes were resolved by magic-angle spinning (MAS). We observed strong proton lipid-ethanol crosspeaks in dispersions of saturated dimyristoylphosphatidylcholine and monounsaturated stearoyloleoylphosphatidylcholine and in polyunsaturated stearoyldocosahexaenoylphosphatidylcholine. Crosspeak intensity has been interpreted in terms of an ethanol distribution function over the lipid bilayer. Ethanol resides with the highest probability at the lipid water interface near the lipid glycerol backbone and upper methylene segments of lipid hydrocarbon chains. Chain unsaturation has only a minor influence on the ethanol distribution function. In all cases, the ethanol concentration in the bilayer core is significantly lower. At ambient temperature all. lipid-ethanol crosspeaks are positive. Crosspeak intensity decreases with increasing water content and increasing temperature most likely because of shorter correlation times of lipid and ethanol reorientation. This suggests a lifetime for specific lipid-ethanol contacts of about 1 ns. Lipid-ethanol and lipid-lipid crosspeaks reflect the high degree of motional disorder of lipids and incorporated ethanol in membranes and the rather arbitrary nature of the location of the lipid-water interface. C1 NIAAA,NIH,LAB MEMBRANE BIOCHEM & BIOPHYS,ROCKVILLE,MD 20852. NR 37 TC 106 Z9 108 U1 0 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 15 PY 1997 VL 36 IS 15 BP 4669 EP 4674 DI 10.1021/bi9626416 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WU189 UT WOS:A1997WU18900036 PM 9109678 ER PT J AU Sgadari, C Farber, JM Angiolillo, AL Liao, F TeruyaFeldstein, J Burd, PR Yao, L Gupta, G Kanegane, C Tosato, G AF Sgadari, C Farber, JM Angiolillo, AL Liao, F TeruyaFeldstein, J Burd, PR Yao, L Gupta, G Kanegane, C Tosato, G TI Mig, the monokine induced by interferon-gamma, promotes tumor necrosis in vivo SO BLOOD LA English DT Article ID EPSTEIN-BARR-VIRUS; X-C CHEMOKINE; INDUCIBLE PROTEIN-10; BURKITTS-LYMPHOMA; IN-VIVO; B-CELLS; FAMILY; IP-10; ANGIOGENESIS; CYTOKINES AB Mig, the monokine induced by interferon-gamma, is a CXC chemokine active as a chemoattractant for activated T cells. Mig is related functionally to interferon-inducible protein 10 (IP-10), with which it shares a receptor, CXCR3, Previously, IP-10 was found to have antitumor activity in vivo, In the present study, murine Mig RNA was found to be expressed at higher levels in regressing Burkitt's lymphoma tumors established in nude mice compared with progressively growing tumors, Daily inoculations of purified recombinant human Mig into Burkitt's tumors growing subcutaneously in nude mice consistently caused tumor necrosis associated with extensive vascular damage. These effects were indistinguishable from those produced by intratumor inoculations of Burkitt's tumors with IP-10, These results support the notion that Mig, like IP-10, has antitumor activity in vivo, This is a US government work. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892. NIAID,CLIN INVEST LAB,NIH,BETHESDA,MD 20892. CHILDRENS NATL MED CTR,DEPT HEMATOL ONCOL,WASHINGTON,DC 20010. NCI,HEMATOPATHOL SECT,PATHOL LAB,BETHESDA,MD 20892. RI Sgadari, Cecilia/H-4302-2016 OI Sgadari, Cecilia/0000-0003-0364-4912 NR 30 TC 205 Z9 207 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 1997 VL 89 IS 8 BP 2635 EP 2643 PG 9 WC Hematology SC Hematology GA WV146 UT WOS:A1997WV14600002 PM 9108380 ER PT J AU Gattei, V Celetti, A Cerrato, A Degan, M DeIuliis, A Rossi, FM Chiappetta, G Consales, C Improta, S Zagonel, V Aldinucci, D Agosti, V Santoro, M Vecchio, G Pinto, A Grieco, M AF Gattei, V Celetti, A Cerrato, A Degan, M DeIuliis, A Rossi, FM Chiappetta, G Consales, C Improta, S Zagonel, V Aldinucci, D Agosti, V Santoro, M Vecchio, G Pinto, A Grieco, M TI Expression of the RET receptor tyrosine kinase and GDNFR-alpha in normal and leukemic human hematopoietic cells and stromal cells of the bone marrow microenvironment SO BLOOD LA English DT Article ID ADULT-RAT TISSUES; GROWTH-FACTOR; DIFFERENTIAL EXPRESSION; NEUROTROPHIC FACTOR; PROTOONCOGENE RET; PROGENITOR CELLS; QUANTITATIVE PCR; PROTO-ONCOGENE; DNA FRAGMENTS; MESSENGER-RNA AB The RET proto-oncogene product is a receptor tyrosine kinase representing the signal-transducing molecule of a multisubunit surface receptor complex for the glial cell line-derived neurotrophic factor (GDNF), in which a novel glycosyl-phosphatidylinositol (PI)-linked protein (termed GDNFR-alpha) acts as the ligand-binding component. We have analyzed expression of RET and GDNFR-alpha in purified normal hematolymphopoietic cells, leukemia/lymphoma cell lines, and 154 primary samples from patients with hematopoietic malignancies encompassing different lineages and differentiation stages. Relatively low amounts of RET mRNA were found in early CD34(+) hematopoietic progenitors, but RET transcripts appeared to increase after myelomonocytic maturation. No expression of RET was found in peripheral blood and tissue B and T lymphocytes. Analysis of human myelomonocytic cell lines was overall consistent with results obtained on purified normal cells. Accordingly, RET expression was mainly confined to acute myeloid leukemias (AMLs) displaying either monocytic (French-American-British M4 and M5) or intermediate-mature myeloid (M2 and M3) phenotypes, being less frequently detected in early myeloid (MO and M1) AMLs. In contrast, RET mRNA was sporadically detected in B-cell tumors, whereas, among T-cell malignancies, RET transcripts were mainly detected in cells of postthymic and mature T-cell phenotype. RET broad detection in primary tumors was not paralleled by the mutual expression of GDNFR-alpha, which was detected only in 2 isolated primary samples and in 3 leukemia/lymphoma cell lines. However, GDNFR-alpha transcripts, in the absence of RET mRNA, were found in normal bone marrow stromal cells (BMSC), in BM fibroblasts, and in two osteoblast cell lines previously described to support normal hematopoiesis. In the presence of GDNF-receptors derived from BMSC by PI-specific phospholipase C cleavage, GDNF efficiently bound RET-expressing AML blasts and was functionally active by reducing their clonogenic growth and triggering the monocytic maturation of leukemic cells. (C) 1997 by The American Society of Hematology. C1 UNIV REGGIO CALABRIA,FAC MED & CHIRURG,DIPARTIMENTO MED SPERIMENTALE & CLIN,I-88100 CATANZARO,ITALY. INRCCS,CTR RIFERIMENTO ONCOL,DIV MED ONCOL,UNITA OPERAT LEUCEMIE & TRAPIANTO MIDOLLO,AVIANO,ITALY. UNIV NAPLES FEDERICO II,FAC MED & CHIRURG,DIPARTIMENTO BIOL & PATOL CELLULARE & MOL,CNR,NAPLES,ITALY. IST TUMORI FDN PASCALE,NAPLES,ITALY. NIH,BETHESDA,MD 20892. RI zagonel, vittorina/F-4226-2014 OI zagonel, vittorina/0000-0002-0829-2525 NR 63 TC 34 Z9 36 U1 0 U2 3 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 APR 15 PY 1997 VL 89 IS 8 BP 2925 EP 2937 PG 13 WC Hematology SC Hematology GA WV146 UT WOS:A1997WV14600035 PM 9108413 ER PT J AU Weijer, C Dickens, B Meslin, EM AF Weijer, C Dickens, B Meslin, EM TI Bioethics for clinicians .10. Research ethics SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Article ID MULTIPLE-MYELOMA; TRIAL AB MEDICAL RESEARCH INVOLVING HUMAN SUBJECTS raises complex ethical, legal and social issues. Investigators sometimes find that their obligations with respect to a research project come into conflict with their obligations to individual patients. The ethical conduct of research rests on 3 guiding principles: respect for persons, beneficence, and justice. Respect for persons underlies the duty to obtain informed consent from study participants. Beneficence demands a favourable balance between the potential benefits and harms of participation. justice requires that vulnerable people not be exploited and that eligible candidates who may benefit from participation not be excluded without good cause. Studies must be designed in a way that ensures the validity of findings and must address questions of sufficient importance to justify the risks of participation. In any clinical trial there must be genuine uncertainty as to which treatment arm offers the most benefit, and placebo controls should not be used if effective standard therapies exist. Researchers have a responsibility to inform themselves about the ethical, legal and policy standards that govern their activities. When difficulties arise, they should consult the existing literature and seek the advice of experts in research ethics. C1 UNIV TORONTO,JOINT CTR BIOETH,TORONTO,ON,CANADA. MCGILL UNIV,MONTREAL,PQ H3A 2T5,CANADA. UNIV TORONTO,FAC MED,TORONTO,ON,CANADA. UNIV TORONTO,FAC LAW,TORONTO,ON,CANADA. NIH,NATL HUMAN GENOME RES INST,ETH LEGAL & SOCIAL IMPLICAT RES PROGRAM,BETHESDA,MD. GEORGETOWN UNIV,KENNEDY INST ETH,WASHINGTON,DC 20057. RP Weijer, C (reprint author), MT SINAI HOSP,600 UNIV AVE,TORONTO,ON M5G 1X5,CANADA. NR 41 TC 30 Z9 32 U1 0 U2 1 PU CANADIAN MEDICAL ASSOCIATION PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA ON K1G 3Y6, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD APR 15 PY 1997 VL 156 IS 8 BP 1153 EP 1157 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA WV101 UT WOS:A1997WV10100036 PM 9141987 ER PT J AU Saku, T Hayashi, Y Takahara, O Matsuura, H Tokunaga, M Tokuoka, S Soda, M Mabuchi, K Land, CE AF Saku, T Hayashi, Y Takahara, O Matsuura, H Tokunaga, M Tokuoka, S Soda, M Mabuchi, K Land, CE TI Salivary gland tumors among atomic bomb survivors, 1950-1987 SO CANCER LA English DT Article DE salivary gland tumor; ionizing radiation; atomic bomb survivors; mucoepidermoid carcinoma; Warthin's tumor ID CANCER INCIDENCE; PAROTID-GLAND; EPIDEMIOLOGIC OBSERVATIONS; HEAD; NECK; IRRADIATION; RADIATION; HIROSHIMA; CARCINOMA; RADIOTHERAPY AB BACKGROUND. Malignant and benign tumors of the salivary glands have been associated with exposure to ionizing radiation from various sources, including the atomic bombings in Hiroshima and Nagasaki. However, questions remain unanswered regarding the nature and size of the risk and specific types of tumors involved. METHODS. The incidence and pathology of malignant and benign tumors of the salivary glands was studied in the Life Span Study cohort of atomic bomb survivors followed by the Radiation Effects Research Foundation (RERF) in Hiroshima and Nagasaki, Japan. Incident cases diagnosed during the period 1950-1987 were ascertained from the tumor and tissue registries of Hiroshima and Nagasaki and supplemented by additional case findings from autopsy, biopsy, and surgical specimens mens maintained at RERF and other institutions. Pathology slides and medical documents were reviewed by a panel of four pathologists who classified tumors using the World Health Organization classification scheme. Analyses were performed of histologic features associated with radiation exposure. RESULTS. Of 145 tumors of the salivary glands identified (119 of the major and 26 of the minor salivary glands), 120 (83%) were histologically confirmed by the current investigators. Among 41 malignant tumors, the frequency of mucoepidermoid tumor was disproportionately high at high radiation doses (P = 0.04); among 94 benign tumors, the frequency of Warthin's tumor increased with increasing radiation dose (P = 0.06). The nature of the tumor was undetermined for the remaining ten cases. Mortality from malignant tumors of the salivary gland was inversely related to radiation dose, reflecting the predominance of mucoepidermoid carcinoma at high dose levels in this series. In one case with high radiation exposure, mucoepidermoid carcinoma of the parotid gland was accompanied by a preexisting or coexisting Warthin's tumor. CONCLUSIONS. These findings, supported by population-based analyses in a companion study reported elsewhere, suggest a causal role for ionizing radiation in salivary gland tumorigenesis, particularly for mucoepidermoid carcinoma, and in the induction of one type of benign tumor (Warthin's tumor). (C) 1997 American Cancer Society. C1 RADIAT EFFECTS RES FDN,DEPT EPIDEMIOL,MINAMI KU,HIROSHIMA 732,JAPAN. NAGASAKI UNIV,SCH DENT,DEPT PATHOL,NAGASAKI 852,JAPAN. HIROSHIMA ASA CITIZENS HOSP,DEPT CLIN LABS,PATHOL SECT,HIROSHIMA,JAPAN. RED CROSS NAGASAKI A BOMB HOSP,DEPT CLIN LABS 2,NAGASAKI,JAPAN. HIROSHIMA CITIZENS HOSP,DEPT PATHOL,HIROSHIMA,JAPAN. KAGOSHIMA CITY HOSP,DEPT PATHOL,KAGOSHIMA,JAPAN. RADIAT EFFECTS RES FDN,DEPT EPIDEMIOL,NAGASAKI,JAPAN. NCI,RADIAT EPIDEMIOL BRANCH,ROCKVILLE,MD. NR 48 TC 61 Z9 61 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 APR 15 PY 1997 VL 79 IS 8 BP 1465 EP 1475 DI 10.1002/(SICI)1097-0142(19970415)79:8<1465::AID-CNCR4>3.0.CO;2-A PG 11 WC Oncology SC Oncology GA WR200 UT WOS:A1997WR20000004 PM 9118025 ER PT J AU Moskaluk, CA Duray, PH Cowan, KH Linehan, M Merino, MJ AF Moskaluk, CA Duray, PH Cowan, KH Linehan, M Merino, MJ TI Immunohistochemical expression of pi-class glutathione S-transferase is down-regulated in adenocarcinoma of the prostate SO CANCER LA English DT Article; Proceedings Paper CT 1993 Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 13-19, 1993 CL NEW ORLEANS, LA SP US & Canadian Acad Pathol DE glutathione S-transferase; prostate carcinoma; prostatic intraepithelial neoplasia; immunohistochemistry ID HUMAN-TISSUES; DRUG-RESISTANCE; LUNG CARCINOMAS; BREAST-CANCER; HUMAN-TUMORS; MOUSE-LIVER; GLYCOPROTEIN; MARKER; IDENTIFICATION; CARCINOGENESIS AB BACKGROUND. Glutathione S-transferase is often up-regulated in neoplastic tissues. A single previous study found a loss of expression associated with carcinogenesis of the prostate. METHODS. To extend these results, the authors performed immunohistochemical staining for the pi-class of glutathione S-transferase (GST pi) on 74 archival sequential prostate specimens. The antibody used was derived from rabbits immunized against purified human GST pi. Paraffin blocks containing both benign tissue and adenocarcinoma were studied. RESULTS. Heterogeneous expression of GST pi in benign acini was found in 96% of cases, but GST pi was not expressed in 95% of invasive adenocarcinomas of the prostate, nor was it expressed in any of the foci of high grade prostatic intraepithelial neoplasia. Basal cells of benign acini showed strong, diffuse staining for GST pi, whereas the secretory luminal epithelium expressed GST pi weakly and focally. CONCLUSIONS. This study confirms the down-regulation of GST pi in adenocarcinoma of the prostate and shows that the loss of GST pi expression is a phenotype associated with malignant transformation. (C) 1997 American Cancer Society. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,MED BRANCH,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. NR 33 TC 52 Z9 55 U1 0 U2 5 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 APR 15 PY 1997 VL 79 IS 8 BP 1595 EP 1599 DI 10.1002/(SICI)1097-0142(19970415)79:8<1595::AID-CNCR23>3.0.CO;2-S PG 5 WC Oncology SC Oncology GA WR200 UT WOS:A1997WR20000023 PM 9118044 ER PT J AU Gemma, A Hagiwara, K Ke, Y Burke, LM Nagashima, HAKM Bennett, WP Harris, CC AF Gemma, A Hagiwara, K Ke, Y Burke, LM Nagashima, HAKM Bennett, WP Harris, CC TI FHIT mutations in human primary gastric cancer SO CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; CHROMOSOMAL REGION 3P21; TUMOR-SUPPRESSOR GENE; SHORT ARM; RENAL-CARCINOMA; HETEROZYGOSITY; DELETION AB Allelic deletion of multiple regions on the short arm of chromosome 3 (3p) implies the presence of multiple important tumor suppressor genes in human carcinogenesis, The FHIT gene, identified recently in chromosome 3p14.2, shows frequent allelic deletion and aberrant transcripts in gastrointestinal tumors, After determining the intron sequences flanking each of the coding exons of the FHIT gene and designing intron primers to facilitate mutation analysis of genomic DNA samples, we analyzed the complete coding sequences in matched cancer and normal tissues from 40 cases with primary gastric cancer using intron primers, PCR-single-strand conformation polymorphism analysis, and direct sequencing. A somatic missense mutation in exon 6, codon 61, ACG (threonine) --> ATG (methionine) was found in a signet ring cell adenocarcinoma. We also evaluated allelic deletion in these tumors by PCR-based microsatellite analysis; allelic deletion occurred in 42.1% (16 of 38) of evaluable cases, This is the first report of a somatic missense mutation of the FHIT gene in a primary tumor, Presence of a point mutation and frequent allelic deletions are consistent with the hypothesis that FHIT gene alterations are involved in the development of primary gastric cancers. C1 NCI,HUMAN CARCINOGENESIS LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. BEIJING MED UNIV,SCH ONCOL,BEIJING 100034,PEOPLES R CHINA. NR 24 TC 96 Z9 112 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 APR 15 PY 1997 VL 57 IS 8 BP 1435 EP 1437 PG 3 WC Oncology SC Oncology GA WT723 UT WOS:A1997WT72300008 PM 9108441 ER PT J AU Wang, LF Ting, CY Lo, CK Su, JS Mickley, LA Fojo, AT WhangPeng, J Hwang, JL AF Wang, LF Ting, CY Lo, CK Su, JS Mickley, LA Fojo, AT WhangPeng, J Hwang, JL TI Identification of mutations at DNA topoisomerase I responsible for camptothecin resistance SO CANCER RESEARCH LA English DT Article ID TUMOR-CELL-LINES; ANTITUMOR DRUGS; POINT MUTATION; YEAST; EXPRESSION; POISONS; MUTANT; GENE; RNA; REPLICATION AB A camptothecin-resistant cell line that exhibits more than 600-fold resistance to camptothecin, designated CPTR-2000, was established from mutagen-treated A2780 ovarian cancer cells, CPTR-2000 cells also exhibit 3-fold resistance to a DNA minor groove-binding ligand Ho33342, a different class of mammalian DNA topoisomerase I inhibitors, However, CPTR-2000 cells exhibit no cross-resistance toward drugs such as Adriamycin, amsacrine, vinblastine. and 4'-dimethyl-epipodophyllotoxin. The mRNA, protein levels, and enzyme-specific activity of DNA topoisomerase I are relatively the same in parental and CPTR-2000 cells, However, unlike the DNA topoisomerase I activity of parental cells, which can be inhibited by camptothecin, that of CPTR-2000 cells cannot, In addition, parental cells after camptothecin treatment results in a decrease in the level of DNA topoisomerase I, whereas CPTR-2000 cells are insensitive to camptothecin treatment, These results suggested that the mechanism of camptothecin resistance is most likely due to a DNA topoisomerase I structural mutation, This notion is supported by DNA sequencing results confirming that DNA topoisomerase I of CPTR-2000 is mutated at amino acid residues Gly(717) to Val and Thr(729) to Ile. We also used the yeast system to examine the mutation(s) responsible for camptothecin resistance, Our results show that each single amino acid change results in partial resistance, and the double mutation gives a synergetic effect on camptothecin resistance. Because both mutation sites are near the catalytic active center, this observation raises the possibility that camptothecin may act at the vicinity of the catalytic active site of the enzyme-camptothecin-DNA complex. C1 ACAD SINICA,INST MOL BIOL,NANKANG,PEOPLES R CHINA. ACAD SINICA,INST BIOMED SCI,NANKANG,PEOPLES R CHINA. TAIPEI MED COLL,DEPT BIOCHEM,TAIPEI,TAIWAN. NCI,MED BRANCH,NIH,BETHESDA,MD 20892. RI Ting, chun-yuan/F-6448-2013 NR 53 TC 48 Z9 48 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 APR 15 PY 1997 VL 57 IS 8 BP 1516 EP 1522 PG 7 WC Oncology SC Oncology GA WT723 UT WOS:A1997WT72300021 PM 9108454 ER PT J AU Chen, AY Okunieff, P Pommier, Y Mitchell, JB AF Chen, AY Okunieff, P Pommier, Y Mitchell, JB TI Mammalian DNA topoisomerase I mediates the enhancement of radiation cytotoxicity by camptothecin derivatives SO CANCER RESEARCH LA English DT Article ID HAMSTER DC3F CELLS; IONIZING-RADIATION; ANTITUMOR DRUGS; POISON CAMPTOTHECIN; CARCINOMA-CELLS; CYTO-TOXICITY; RESISTANCE; TOPOTECAN; INVITRO; IDENTIFICATION AB The role of DNA topoisomerase I as a biochemical mediator of radiosensitization in cultured mammalian cells by camptothecin derivatives was studied, We found that, in Chinese hamster DC3F cells, camptothecin enhanced the cytotoxicity of radiation in a schedule-dependent manner, At 4 mu M, a sensitizer enhancement ratio of 1.45 was observed when radiation was used concurrently with or immediately after drug treatment, By comparison, no enhancement was obtained if radiation preceded camptothecin treatment, Consistently, in human breast cancer MCF-7 cells, sensitizer enhancement ratios of 1.43, 1.38, and 1.05 were observed when radiation was used concurrently with, immediately after, or prior to treatment with 20(S)-10,11-methylenedioxycamptothecin (MDCamp). Three studies indicated that an intact stereospecific interaction between camptothecin derivatives and DNA topoisomerase I is essential in the induction of radiosensitization: (a) higher concentrations of camptothecin were required to radiosensitize the camptothecin-resistant DC3F/C-10 cells; (b) a newly identified topoisomerase I-targeting Hoechst 33342 also radiosensitized DC3F cells; and (c) 20 (S)-methylenedioxycamptothecin, but not its noncytotoxic 20(R)-stereoisomer, radiosensitized MCF-7 cells by obliterating the ''shoulder'' of the radiation survival curve, The mechanism of radiosensitization was investigated in DC3F cells, We found that camptothecin only minimally enhanced the cytoxic effect of radiation in G(1)-phase cells obtained by a mitotic shake-off technique as well as in plateau-phase cells arrested by growing to confluency, Our data suggest a potential development of topoisomerase I drugs as radiosensitizers in treating human malignancies. C1 NCI,MOL PHARMACOL LAB,NIH,BETHESDA,MD 20892. NCI,RADIAT BIOL BRANCH,NIH,BETHESDA,MD 20892. RP Chen, AY (reprint author), NCI,RADIAT ONCOL BRANCH,NIH,BLDG 10,ROOM B3B69,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 47 TC 60 Z9 61 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 1997 VL 57 IS 8 BP 1529 EP 1536 PG 8 WC Oncology SC Oncology GA WT723 UT WOS:A1997WT72300023 PM 9108456 ER PT J AU Kuukasjarvi, T Karhu, R Tanner, M Kahkonen, M Schaffer, A Nupponen, N Pennanen, S Kallioniemi, A Kallioniemi, OP Isola, J AF Kuukasjarvi, T Karhu, R Tanner, M Kahkonen, M Schaffer, A Nupponen, N Pennanen, S Kallioniemi, A Kallioniemi, OP Isola, J TI Genetic heterogeneity and clonal evolution underlying development of asynchronous metastasis in human breast cancer SO CANCER RESEARCH LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; POLYMERASE CHAIN-REACTION; SEQUENCE COPY NUMBER; TUMOR-METASTASIS; CARCINOMAS; DNA; AMPLIFICATION; LOSSES; ORIGIN; CELLS AB To understand the genetic basis and clonal evolution underlying metastatic progression of human breast cancer in vivo, we analyzed the genetic composition of 29 primary breast carcinomas and their paired asynchronous metastases by comparative genomic hybridization and fluorescence in situ hybridization, The mean number of genetic changes by comparative genomic hybridization was 8.7 +/- 5.3 in primary tumors and 9.0 +/- 5.7 in their metastases, Although most of the genetic changes occurred equally often in the two groups, gains of the Xq12-q22 region were enriched in the metastases, According to a statistical analysis of shared genetic changes and breakpoints in paired specimens, 20 of the metastases (69%) showed a high degree of clonal relationship with the corresponding primary tumor, whereas the genetic composition of 9 metastases (31%) differed almost completely from that of the paired primary tumors, In both groups, however, chromosome X inactivation patterns suggested that the metastatic lesions originated from the same clone as the primary tumor, Fluorescence in situ hybridization analysis with probes specific to metastatic clones usually failed to find such cells in the primary tumor sample, In conclusion, detailed characterization of the in vivo progression pathways of metastatic breast cancer indicates that a linear progression model is unlikely to account for the progression of primary tumors to metastases, An early stem line clone apparently evolves independently in the primary tumor and its metastasis, eventually leading to multiple, genetically almost completely different, clones in the various tumor locations in a given patient, The resulting heterogeneity of metastatic breast cancer may underlie its poor responsiveness to therapy and explain why biomarkers of prognosis or therapy responsiveness measured exclusively from primary tumors give a restricted view of the biological properties of metastatic breast cancer. C1 TAMPERE UNIV HOSP,DEPT PATHOL,FIN-33521 TAMPERE,FINLAND. TAMPERE UNIV,INST MED TECHNOL,FIN-33521 TAMPERE,FINLAND. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP Kuukasjarvi, T (reprint author), TAMPERE UNIV HOSP,CANC GENET LAB,POB 2000,FIN-33521 TAMPERE,FINLAND. RI Kallioniemi, Olli/H-5111-2011; Schaffer, Alejandro/F-2902-2012; Kallioniemi, Olli/H-4738-2012; OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Anne/0000-0003-3552-8158 NR 40 TC 298 Z9 304 U1 0 U2 6 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 APR 15 PY 1997 VL 57 IS 8 BP 1597 EP 1604 PG 8 WC Oncology SC Oncology GA WT723 UT WOS:A1997WT72300033 PM 9108466 ER PT J AU Pepe, S Xiao, RP Hohl, C Altschuld, R Lakatta, EG AF Pepe, S Xiao, RP Hohl, C Altschuld, R Lakatta, EG TI 'Cross talk' between opioid peptide and adrenergic receptor signaling in isolated rat heart SO CIRCULATION LA English DT Article DE opioid peptides; receptors, adrenergic, beta; cAMP; proteins; rats ID CYCLIC ADENOSINE-MONOPHOSPHATE; PROENKEPHALIN MESSENGER-RNA; ADENYLATE-CYCLASE; CARDIAC MYOCYTES; PHOSPHOINOSITIDE HYDROLYSIS; PROTEIN-PHOSPHORYLATION; VENTRICULAR MYOCYTES; PERTUSSIS-TOXIN; CELLS; STIMULATION AB Background Cardiac myocyte sarcolemma contains both catecholamine and opioid peptide receptors (OPRs). Opioid peptides are coreleased with catecholamines from nerve terminals in the heart. We investigated whether OPR stimulation influences the effects of beta-adrenergic receptor (beta-AR) stimulation in the isolated, isovolumic rat heart and whether the mechanism of such an interaction involves both beta-AR subtypes or an alteration in beta-AR-mediated increase in cAMP. Methods and Results Norepinephrine (NE, 10(-7) mol/L) in creased peak left ventricular systolic pressure (LVSP) and cAMP more than twofold compared with controls. The delta-OPR agonist leucine-enkephalin (LE, 10(-8) mol/L) markedly inhibited the beta(1)-AR-induced positive inotropic effect and increase in cAMP but alone had no effect on basal LVSP or basal cAMP levels. The OPR antagonist naloxone 10(-8) mol/L added to LE+NE perfusate reversed the LE-induced decrease in cAMP and LVSP even though naloxone alone had no effect on LVSP and cAMP levels. LE could not counteract the twofold increase in LVSP produced by the nondegradable cAMP analog CPT-cAMP 2.3x10(-5) mol/L or a high concentration of forskolin (10(-7) mol/L) but did reverse the 173+/-11.8% and 135+/-13.6% increases in LVSP stimulated by 10(-8) and 0.5x10(-8) mol/L forskolin, respectively. LE inhibited cAMP production at all concentrations of forskolin (10(-7), 10(-8), and 0.5x10(-8) mol/L). Pertussis toxin (PTX) pretreatment abolished LE effects on beta(1)-AR stimulation. Zinterol 10(-5) and 10(-6) mol/L, a specific beta(2)-AR agonist that elicits a cAMP-independent inotropic effect in rat heart, caused 225+/-14% and 182+/-5% increases in LVSP that could not be reversed by addition of LE. Conclusions Potent, inhibitory ''cross talk'' between delta-OPR and beta(1)-AR signaling pathways occurs via a PTX-sensitive G(i/o) protein involved in adenylyl cyclase inhibition in rat heart. C1 NIA,CARDIOVASC SCI LAB,CTR GERONTOL RES,BALTIMORE,MD 21224. OHIO STATE UNIV,DEPT MED BIOCHEM,COLUMBUS,OH 43210. FU NHLBI NIH HHS [HL-48835] NR 55 TC 68 Z9 74 U1 0 U2 4 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 15 PY 1997 VL 95 IS 8 BP 2122 EP 2129 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA WU760 UT WOS:A1997WU76000027 PM 9133523 ER PT J AU Cutler, RE Morrison, DK AF Cutler, RE Morrison, DK TI Mammalian Raf-1 is activated by mutations that restore Raf signaling in Drosophila SO EMBO JOURNAL LA English DT Article DE activation; mutation; Raf-1; Ras; signaling ID TERMINAL REGULATORY DOMAIN; DEPENDENT PROTEIN-KINASE; MAP KINASE; PHOSPHORYLATION SITES; TRANSDUCTION PATHWAY; CATALYTIC SUBUNIT; XENOPUS-OOCYTES; PLASMA-MEMBRANE; IDENTIFICATION; 14-3-3-PROTEINS AB An interaction with the Ras proto-oncogene product is a requirement for Raf-1 activation in many signaling cascades, The significance of this interaction is demonstrated by the fact that a mutation preventing the Ras-Raf interaction severely impairs the function of both mammalian (Raf-1) and Drosophila (D-Raf) Raf proteins, In D-Raf, however, dominant intragenic mutations have been identified that suppress the effect of the Ras-binding site (RES) mutation, To address the mechanism by which these mutations restore Raf signaling, we have introduced the suppressor mutations into the analogous residues of mammalian Raf-1. Here, we show that rather than compensating for the RES mutation by restoring the Ras-Raf-1 interaction, the suppressor mutations increase the enzymatic and biological activity of Raf-1, allowing Raf-1 to signal in the absence of Ras binding, Surprisingly, we find that while one of the suppressor mutations (P181L) increases the basal kinase activity of Raf-1, it also abolishes the ability of wild-type Raf-1 to become activated by Ras, This mutation occurs in the cysteine-rich domain (CRD) of Raf-1 and demonstrates the importance of this region for a productive Ras-Raf interaction, Finally, we present evidence that the most activating suppressor mutation (G498S) increases Raf-1 activity by introducing a novel phosphorylation site into the L-12 activation loop of the Raf-1 kinase domain. RP NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, MOL BASIS CARCINOGENESIS LAB, FREDERICK, MD 21702 USA. NR 52 TC 15 Z9 15 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD APR 15 PY 1997 VL 16 IS 8 BP 1953 EP 1960 DI 10.1093/emboj/16.8.1953 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WV896 UT WOS:A1997WV89600015 PM 9155021 ER PT J AU Ura, K Kurumizaka, H Dimitrov, S Almouzni, G Wolffe, AP AF Ura, K Kurumizaka, H Dimitrov, S Almouzni, G Wolffe, AP TI Histone acetylation: Influence on transcription, nucleosome mobility and positioning, and linker histone-dependent transcriptional repression SO EMBO JOURNAL LA English DT Review DE acetylation; histones; nucleosome mobility; nucleosome positioning; transcriptional regulation ID NEWLY REPLICATED CHROMATIN; LINKING NUMBER CHANGE; TATA-BINDING PROTEIN; DNASE-I SENSITIVITY; 5S RNA GENE; FACILITATED BINDING; AMINO TERMINI; CORE PARTICLE; POSITIVE ROLE; C-FOS AB We demonstrate using a dinucleosome template that acetylation of the core histones enhances transcription by RNA polymerase III. This effect is not dependent on an increased mobility of the core histone octamer with respect to DNA sequence. When linker histone is subsequently bound, we find both a reduction in nucleosome mobility and a repression of transcription. These effects of linker histone binding are independent of core histone acetylation, indicating that core histone acetylation does not prevent linker histone binding and the concomitant transcriptional repression. These studies are complemented by the use of a Xenopus egg extract competent both for chromatin assembly on replicating DNA and for RNA polymerase III transcription. Incorporation of acetylated histones and lack of linker histones together facilitate transcription by >10-fold in this system; however, they have little independent effect on transcription. Thus core histone acetylation significantly facilitates transcription, but this effect is inhibited by the assembly of linker histones into chromatin. C1 NICHHD,NIH,MOL EMBRYOL LAB,BETHESDA,MD 20892. RI dimitrov, stefan/M-7697-2013 NR 108 TC 186 Z9 187 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD APR 15 PY 1997 VL 16 IS 8 BP 2096 EP 2107 DI 10.1093/emboj/16.8.2096 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WV896 UT WOS:A1997WV89600029 PM 9155035 ER PT J AU Holloway, AJ Della, NG Fletcher, CF Largespada, DA Copeland, NG Jenkins, NA Bowtell, DDL AF Holloway, AJ Della, NG Fletcher, CF Largespada, DA Copeland, NG Jenkins, NA Bowtell, DDL TI Chromosomal mapping of five highly conserved murine homologues of the Drosophila RING finger gene seven-in-absentia SO GENOMICS LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAY; PROTEIN TYROSINE KINASE; LINKAGE MAP; INTERSPECIFIC BACKCROSS; MOUSE CHROMOSOME-8; LEUKEMIA-VIRUS; ZINC-FINGER; EXPRESSION; LOCUS; RAS1 AB Seven-in-absentia (sina) is epistatic to all other known genes in the sevenless-ras signaling pathway, which mediates R7 photoreceptor formation in the Drosophila eye. The murine genome contains several closely related sina homologues (Siah1A-D, Siah2) that are also likely to participate in ras signaling. As part of a genetic and biochemical analysis of the mammalian Siah genes, we have used gene-specific probes to map the chromosomal positions of each family member. Here we report their chromosomal positions in relation to a number of known mouse mutations and also describe an analysis of the human Siah genes. By comparing the complexity of the Siah genes in these two mammalian species we have gained further insight into which members of this murine multigene family are likely to be functional. (C) 1997 Academic Press. C1 PETER MACCALLUM CANC INST,TRESCOWTHICK RES LABS,MELBOURNE,VIC 3000,AUSTRALIA. UNIV MELBOURNE,DEPT BIOCHEM & MOL BIOL,PARKVILLE,VIC 3052,AUSTRALIA. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RI Bowtell, David/H-1007-2016 OI Bowtell, David/0000-0001-9089-7525 NR 39 TC 29 Z9 30 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD APR 15 PY 1997 VL 41 IS 2 BP 160 EP 168 DI 10.1006/geno.1997.4642 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WU556 UT WOS:A1997WU55600003 PM 9143490 ER PT J AU Castillo, SO Xiao, QX Lyu, MS Kozak, CA Nikodem, VM AF Castillo, SO Xiao, QX Lyu, MS Kozak, CA Nikodem, VM TI Organization, sequence, chromosomal localization, and promoter identification of the mouse orphan nuclear receptor Nurr1 gene SO GENOMICS LA English DT Article ID NERVE GROWTH-FACTOR; NGFI-B NUR77; MEMBRANE DEPOLARIZATION; TRANSCRIPTIONAL ACTIVATION; INDUCIBLE MEMBER; PC12 CELLS; C-FOS; SUPERFAMILY; EXPRESSION; BINDING AB We have cloned and characterized the organization of the mouse orphan nuclear receptor Nurr1 gene. The Nurr1 gene is approximately 7 kb long, contains eight exons and seven introns, and mapped to mouse chromosome 2. Although the exon/intron structure of Nurr1 is nearly identical to that of Nur77, Nurr1 possesses an additional untranslated exon. Primer extension was used to identify two major transcription initiation sites mapped 37 nucleotides apart in the first untranslated exon. Functional studies of chimeric Nurr1-luciferase reporter genes delineated the promoter region and underscored the importance of the +1 transcription start site. Sequence analysis of the 5' flanking region surrounding +1 revealed several possible response elements such as a hexanucleotide glucocorticoid binding site, a cAMP-response element, a CArG box, and two c-Jun-binding sites. These data help to explain the different response characteristics of two closely related early response genes, Nurr1 and Nur77. (C) 1997 Academic Press. C1 NIDDK,NIH,BETHESDA,MD 20892. NIAID,NIH,BETHESDA,MD 20892. NR 43 TC 33 Z9 35 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD APR 15 PY 1997 VL 41 IS 2 BP 250 EP 257 DI 10.1006/geno.1997.4677 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WU556 UT WOS:A1997WU55600014 PM 9143501 ER PT J AU Turtzo, LC Lee, MD Lu, MQ Smith, BL Copeland, NG Gilbert, DJ Jenkins, NA Agre, P AF Turtzo, LC Lee, MD Lu, MQ Smith, BL Copeland, NG Gilbert, DJ Jenkins, NA Agre, P TI Cloning and chromosomal localization of mouse Aquaporin 4: Exclusion of a candidate mutant phenotype, ataxia SO GENOMICS LA English DT Article ID CDNA AB Aquaporin-4 is a mammalian water channel protein that is predominately expressed in brain, where it is believed to mediate water homeostasis. Here we report the isolation and characterization of the cDNA for mouse Aqp4 and map the gene to the proximal region of mouse chromosome 18. This region contains the neurological mutation ataxia, but further analysis reveals that Aqp4 is not responsible for the ataxia phenotype. (C) 1997 Academic Press. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT BIOL CHEM,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DIV PULM & CRIT CARE MED,BALTIMORE,MD 21205. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FU NHLBI NIH HHS [HL3391, HL48268]; NIGMS NIH HHS [GM07309] NR 15 TC 23 Z9 26 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD APR 15 PY 1997 VL 41 IS 2 BP 267 EP 270 DI 10.1006/geno.1997.4641 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WU556 UT WOS:A1997WU55600017 PM 9143504 ER PT J AU Savary, S Allikmets, R Denizot, F Luciani, MF Mattei, MG Dean, M Chimini, G AF Savary, S Allikmets, R Denizot, F Luciani, MF Mattei, MG Dean, M Chimini, G TI Isolation and chromosomal mapping of a novel ATP-binding cassette transporter conserved in mouse and human SO GENOMICS LA English DT Article ID MEMBRANE; YEAST AB We report here on the identification and genomic mapping of a novel member of the family of the ATP-binding cassette (ABC) transporters, ABC7, conserved in mouse and in humans. The ABC7 gene encodes a protein with the typical features of half-transporters, such as those involved in translocation of antigenic peptides or in peroxisomal disorders. ABC7 shows a ubiquitous expression pattern and maps to the X chromosome both in mouse and in humans. The high sequence similarity to those of two yeast half-transporters supports once again the extreme evolutionary conservation of this family of proteins. (C) 1997 Academic Press. C1 CNRS,INSERM,CTR IMMUNOL,F-13288 MARSEILLE 09,FRANCE. CNRS UPR9043,F-13288 MARSEILLE,FRANCE. INSERM 406,F-13288 MARSEILLE,FRANCE. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. RI Savary, Stephane/C-8137-2011; Dean, Michael/G-8172-2012 OI Savary, Stephane/0000-0002-9237-1727; Dean, Michael/0000-0003-2234-0631 NR 13 TC 29 Z9 30 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD APR 15 PY 1997 VL 41 IS 2 BP 275 EP 278 DI 10.1006/geno.1997.4658 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA WU556 UT WOS:A1997WU55600019 PM 9143506 ER PT J AU Pueyo, S Salmi, LR Chene, G Leport, C Morlat, P Dequae, L Gregoire, V Hafner, R Vilde, JL Luft, BJ Aubertin, J Salamon, R AF Pueyo, S Salmi, LR Chene, G Leport, C Morlat, P Dequae, L Gregoire, V Hafner, R Vilde, JL Luft, BJ Aubertin, J Salamon, R TI Survival after AIDS-defining events in patients with <200 lymphocytes CD4+x10(6)/L who are toxoplasmosis antibody positive SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE prognosis; HIV infection; Pneumocystis carinii pneumonia; toxoplasmosis; cytomegalovirus infection; survival ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; NERVOUS-SYSTEM TOXOPLASMOSIS; INFECTED PERSONS; HOMOSEXUAL MEN; COUNT; ENCEPHALITIS; PROGRESSION; MARKERS; DISEASE; MODELS AB The objective of this study was to assess whether patients with CD4+ cell counts <200 x 10(6)/L have a decreased survival after the occurrence of any AIDS-defining event; 187 patients from the placebo arm of a clinical trial of toxoplasmosis prophylaxis (ANRS005-ACTG154) were included. For this analysis, patients were HIV infected without any AIDS-defining event, had a CD4+ lymphocyte count <200 x 10(6)/L, had a positive serology for Toxoplasma gondii, and had no severe liver, renal, or hematologic abnormalities. We used proportional hazards regression to study the relationships between baseline variables. AIDS-defining events as time-dependent variables, and survival. The risk of dying was increased by 1.9 for a 10-year increase in age and by 1.3 when CD4(+) decreased by 50 x 10(6)/L; after the occurrence of a pneumocystosis, a cytomegalovirus infection, or a toxoplasmosis, the risk of dying was multiplied, respectively, by 10.9 (3.0-40.2), 10.0 (2.8-35.4), and 10.0 (4.5-22.2). None of the other AIDS-defining events was associated with an increased risk of dying, but the power to detect such an association was limited. We conclude that the occurrence of pneumocystosis, cytomegalovirus infection, or toxoplasmosis; age; and CD4+ cell count are important determinants of survival for HIV1-infected patients with CD4+ counts <200 X 10(6)/L who are toxoplasmosis antibody positive. C1 HOP BICHAT CLAUDE BERNARD,SERV MALAD INFECT & TROP,F-75877 PARIS 18,FRANCE. HOP ST ANDRE,SERV MED INTERNE,BORDEAUX,FRANCE. NIAID,DIV AIDS,BETHESDA,MD 20892. SUNY STONY BROOK,HLTH SCI CTR T 15 080,DEPT MED,DIV INFECT DIS,STONY BROOK,NY 11794. HOP PELLEGRIN,SERV MALAD INFECT,F-33076 BORDEAUX,FRANCE. RP Pueyo, S (reprint author), UNIV BORDEAUX 2,DEPT MED INFORMAT,INSERM U330,146 RUE LEO SAIGNAT,F-33076 BORDEAUX,FRANCE. RI chene, genevieve/H-8665-2014; OI Luft, Benjamin/0000-0001-9008-7004 NR 31 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 15 PY 1997 VL 14 IS 5 BP 459 EP 464 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA XC491 UT WOS:A1997XC49100010 PM 9170421 ER PT J AU Ecelbarger, CA Nielsen, S Olson, BR Murase, T Baker, EA Knepper, MA Verbalis, JG AF Ecelbarger, CA Nielsen, S Olson, BR Murase, T Baker, EA Knepper, MA Verbalis, JG TI Role of renal aquaporins in escape from vasopressin-induced antidiuresis in rat SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE antidiuretic hormone; urinary concentrating mechanism; water channels; hyponatremia; SIADH ID KIDNEY COLLECTING DUCT; INSENSITIVE WATER CHANNEL; MOLECULAR-CLONING; EXPRESSION; MEMBRANE; GLYCEROL; IMMUNOLOCALIZATION; PERMEABILITY; BALANCE; PROTEIN AB The purpose of this study was to investigate whether escape from vasopressin-induced antidiuresis is associated with altered regulation of any of the known aquaporin water channels. After 4-d pretreatment with 1-deamino-[8-D-arginine]-vasopressin (dDAVP) by osmotic mini-pump, rats were divided into two groups: control (continued dDAVP) and water-loaded (continued dDAVP plus a daily oral water load). A significant increase in urine volume in the water-loaded rats was observed by the second day of water loading, indicating onset of vasopressin escape. The onset of escape coincided temporally with a marked decrease in renal aquaporin-2 protein (measured by semiquantitative immunoblotting), which began at day 2 and fell to 17% of control levels by day 3. In contrast, there was no decrease in the renal expression of aquaporins 1, 3, or 4. The marked suppression of whole kidney aquaporin-2 protein was accompanied by a concomitant suppression of whole kidney aquaporin-2 mRNA levels. Immunocytochemical localization and differential centrifugation studies demonstrated that trafficking of aquaporin-2 to the plasma membrane remained intact during vasopressin escape. The results suggest that escape from vasopressin-induced antidiuresis is attributable, at least in part, to a vasopressin-independent decrease in aquaporin-2 water channel expression in the renal collecting duct. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,NIH,BETHESDA,MD 20892. AARHUS UNIV,INST ANAT,DEPT CELL BIOL,DK-8000 AARHUS,DENMARK. GEORGETOWN UNIV,DIV ENDOCRINOL,WASHINGTON,DC 20007. WATERBURY HOSP & HLTH CTR,WATERBURY,CT 06708. FU NIDDK NIH HHS [DK-38094] NR 33 TC 165 Z9 167 U1 1 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR 15 PY 1997 VL 99 IS 8 BP 1852 EP 1863 DI 10.1172/JCI119352 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA WV360 UT WOS:A1997WV36000008 PM 9109429 ER PT J AU Mickley, LA Spengler, BA Knutsen, TA Biedler, JL Fojo, T AF Mickley, LA Spengler, BA Knutsen, TA Biedler, JL Fojo, T TI Gene rearrangement: A novel mechanism for MDR-1 gene activation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE drug resistance; P-glycoprotein; MDR-1; gene rearrangements ID P-GLYCOPROTEIN GENE; CCAAT DISPLACEMENT PROTEIN; KB CARCINOMA-CELLS; MULTIDRUG-RESISTANCE; TUMOR-CELLS; EXPRESSION; LINES; MDR-1/P-GLYCOPROTEIN; AMPLIFICATION; PERMEABILITY AB Drug resistance, a major obstacle to cancer chemotherapy, can be mediated by MDR-1/P-glycoprotein. Deletion of the first 68 residues of MDR-1 in an adriamycin-selected cell line after a 4;7 translocation, t(4q;7q), resulted in a hybrid mRNA containing sequences from both MDR-1 and a novel chromosome 4 gene. Further selection resulted in amplification of a hybrid gene. Expression of the hybrid mRNA was controlled by the chromosome 4 gene, providing a model for overexpression of MDR-1. Additional hybrid mRNAs in other drug-selected cell lines and in patients with refractory leukemia, with MDR-1 juxtaposed 3' to an active gene, establishes random chromosomal rearrangements with overexpression of hybrid MDR-1 mRNAs as a mechanism of acquired drug resistance. C1 NCI,DCS,MED BRANCH,BETHESDA,MD 20892. MEM SLOAN KETTERING CANC RES INST,NEW YORK,NY 10021. NR 32 TC 76 Z9 78 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR 15 PY 1997 VL 99 IS 8 BP 1947 EP 1957 DI 10.1172/JCI119362 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA WV360 UT WOS:A1997WV36000018 PM 9109439 ER PT J AU Sevransky, JE Shaked, G Novogrodsky, A Levitzki, A Gazit, A Hoffman, A Elin, RJ Quezado, ZMN Freeman, BD Eichacker, PQ Danner, RL Banks, SM Bacher, J Thomas, ML Natanson, C AF Sevransky, JE Shaked, G Novogrodsky, A Levitzki, A Gazit, A Hoffman, A Elin, RJ Quezado, ZMN Freeman, BD Eichacker, PQ Danner, RL Banks, SM Bacher, J Thomas, ML Natanson, C TI Tyrphostin AG 556 improves survival and reduces multiorgan failure in canine Escherichia coli peritonitis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE tyrosine kinase; inhibitor cell signaling pathways; septic shock; multiorgan failure ID TUMOR-NECROSIS-FACTOR; HUMAN SEPTIC SHOCK; INTERLEUKIN-1 RECEPTOR ANTAGONIST; TYROSINE KINASE INHIBITORS; HUMAN MONOCLONAL-ANTIBODY; GRAM-NEGATIVE BACTEREMIA; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; SEPSIS SYNDROME; EGF RECEPTOR AB Tyrosine kinase-dependent cell signaling is postulated to be a pivotal control point in inflammatory responses initiated by bacterial products and TNF. Using a canine model of gram-negative septic shock, we investigated the effect of tyrosine kinase inhibitors (tyrphostins) on survival. Animals were infected intraperitoneally with Escherichia coli 0111: B4, and then, in a randomized, blinded fashion, were treated immediately with one of two tyrphostins, AG 556 (n = 40) or AG 126 (n = 10), or with control (n = 50), and followed for 28 d or until death. All animals received supplemental oxygen, fluids, and antibiotics. Tyrphostin AG 556 improved survival times when compared to controls (P = 0.05). During the first 48 h after infection, AG 556 also improved mean arterial pressure, left ventricular ejection fraction, cardiac output, oxygen delivery, and alveolar-arterial oxygen gradient compared to controls (all P less than or equal to 0.05). These improvements in organ injury were significantly predictive of survival. Treatment with AG 556 had no effect on clearance of endotoxin or bacteria from the blood (both P = NS); however, AG 556 did significantly lower serum TNF levels (P = 0.03). These data are consistent with the conclusion that AG 556 prevented cytokine-induced multiorgan failure and death during septic shock by inhibiting cell-signaling pathways without impairing host defenses as determined by clearance of bacteria and endotoxin. C1 NIH,DEPT CLIN PATHOL,BETHESDA,MD 20892. NIH,VET RESOURCES PROGRAM,BETHESDA,MD 20892. TEL AVIV UNIV,SACKLER FAC MED,IL-69978 TEL AVIV,ISRAEL. FELSENSTEIN MED RES CTR,PETAH TIQWA,ISRAEL. HEBREW UNIV JERUSALEM,DEPT BIOL CHEM,IL-91904 JERUSALEM,ISRAEL. HEBREW UNIV JERUSALEM,DEPT PHARMACEUT,IL-91904 JERUSALEM,ISRAEL. RP Sevransky, JE (reprint author), NIH,DEPT CRIT CARE MED,BLDG 10,ROOM 7D-43,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 NR 39 TC 47 Z9 47 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR 15 PY 1997 VL 99 IS 8 BP 1966 EP 1973 DI 10.1172/JCI119364 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA WV360 UT WOS:A1997WV36000020 PM 9109441 ER PT J AU Loftus, DJ Chen, Y Covell, DG Engelhard, VH Appella, E AF Loftus, DJ Chen, Y Covell, DG Engelhard, VH Appella, E TI Differential contact of disparate class I peptide complexes as the basis for epitope cross-recognition by a single T cell receptor SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOXIC LYMPHOCYTES-T; MOLECULAR MIMICRY; VIRAL PEPTIDES; ENDOGENOUS PEPTIDE; MHC COMPLEXES; SELF-PEPTIDE; ANTIGEN; PROTEIN; BINDING; IDENTIFICATION AB In an effort to better understand functional recognition of structurally dissimilar ligands by a single TCR, a model system for studying cross-recognition of disparate peptide/class I complexes was developed using the murine (H-2(b)) CTL clone AHIII12.2, which is reactive to a human self-peptide (p1049) bound to an HLA-A2.1 molecule. We identified a second complex comprised of a synthetic peptide, designated p1058, bound to H-2D(b) that is recognized by clone AHIII12.2. In cytolysis assays, dose-response profiles for peptides p1049 and p1058 pulsed onto the appropriate target cells were comparable, suggesting that p1049/A2.1 and p1058/D-b form functionally equivalent epitopes. To probe the interaction between each complex and the TCR of AHIII12.2, singly substituted analogues of each peptide were tested for their activity in lysis assays. Differences were observed between the two epitopes with respect to permissible residue substitutions at each peptide position from P3 to P8; marked differences were evident at P3 and at P8. The results obtained suggest that this TCR forms critical contacts with atoms at peptide positions P3 and P5 of p1049/A2.1 and at P5 and P8 of p1058/D-b, and that TCR cross-recognition of these ligands is a function of both shared and complex-specific contacts made with each epitope. These findings further highlight the versatile reactivity that may be shown by a single TCR and suggest a basis for the recognition of peptide ligands sharing only a limited set of structural features. C1 UNIV VIRGINIA,BEIRNE CARTER CTR IMMUNOL RES,CHARLOTTESVILLE,VA 22908. NCI,MATH BIOL LAB,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. RP Loftus, DJ (reprint author), NCI,CELL BIOL LAB,NIH,BLDG 37,ROOM 1B03,37 CONVENT DR,MSC 4255,BETHESDA,MD 20892, USA. NR 52 TC 35 Z9 36 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 APR 15 PY 1997 VL 158 IS 8 BP 3651 EP 3658 PG 8 WC Immunology SC Immunology GA WT196 UT WOS:A1997WT19600014 PM 9103427 ER PT J AU Vergelli, M Hemmer, B Kalbus, M Vogt, AB Ling, N Conlon, P Coligan, JE McFarland, H Martin, R AF Vergelli, M Hemmer, B Kalbus, M Vogt, AB Ling, N Conlon, P Coligan, JE McFarland, H Martin, R TI Modifications of peptide ligands enhancing T cell responsiveness imply large numbers of stimulatory ligands for autoreactive T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; RECEPTOR LIGAND; RECOGNITION; AUTOIMMUNITY; PROLIFERATION; SEPARATION; COMPLEXES; MIMICRY; ANERGY; CLONES AB In this report, we demonstrate for autoreactive T cell clones that single amino acid modifications of the antigenic ligand can result in not only abrogated, decreased, or unmodified, but also increased, T cell responsiveness (superagonist ligands). We further studied the effects of combinations of multiple substitutions with different effects in single peptides. Experiments with peptides carrying multiple amino acid exchanges revealed that the final outcome of TCR ligation by a given ligand is the integration of negative, neutral, and positive effects of each single residue, In addition, the introduction of superagonist substitutions together with nonconservative modifications of primary and secondary TCR contacts resulted in stimulatory ligands, These findings indicate that: 1) the specificity of a single TCR is highly degenerate; 2) ligands exist for autoreactive T cells that have higher agonist activity than the autoantigen itself; 3) the rules to search for cross-reactive epitopes in autoimmunity should take into account that amino acids at certain positions within an antigenic peptide may exert superagonist activity and compensate for the negative effects of residues at other positions that would otherwise not be tolerated. C1 NINCDS,NIH,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. UNIV TUBINGEN,DEPT NEUROL,D-7400 TUBINGEN,GERMANY. GERMAN CANC RES CTR,TUMOR IMMUNOL PROGRAMME,DIV SOMAT GENET,D-6900 HEIDELBERG,GERMANY. NEUROCRINE BIOSCI INC,SAN DIEGO,CA 92121. NIAID,MOL STRUCT LAB,NIH,ROCKVILLE,MD 20892. NR 22 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 APR 15 PY 1997 VL 158 IS 8 BP 3746 EP 3752 PG 7 WC Immunology SC Immunology GA WT196 UT WOS:A1997WT19600026 PM 9103439 ER PT J AU Shaikh, N Rivera, J Hewlett, BR Stead, RH Zhu, FG Marshall, JS AF Shaikh, N Rivera, J Hewlett, BR Stead, RH Zhu, FG Marshall, JS TI Mast cell Fc epsilon RI expression in the rat intestinal mucosa and tongue is enhanced during Nippostrongylus brasiliensis infection and can be up-regulated by in vivo administration of IgE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BASOPHILIC LEUKEMIA-CELLS; PROTEIN-TYROSINE PHOSPHORYLATION; EPIDERMAL LANGERHANS CELLS; HIGH-AFFINITY RECEPTOR; IMMUNOGLOBULIN-E; BETA-SUBUNIT; SIGNAL TRANSDUCTION; CROSS-LINKING; TNF-ALPHA; DIFFERENTIATION AB The activation of rodent and human mast cells can occur through the cross-linking of tetrameric IgE receptors each containing single alpha- and beta- and two gamma-subunits. However, the factors that regulate the in vivo expression of Fc epsilon RI are poorly understood. We have examined the expression of the Fc epsilon RI beta-subunit in the Nippostrongylus brasiliensis (Nb)-induced model of rat intestinal inflammation. We developed a double-staining technique for mast cell granules (Alcian blue) and the beta-subunit of Fc epsilon RI. The intensity of immunohistochemical staining per mast cell was quantified using an image analysis system. Jejunal and tongue mast cells of Lewis rats were visible by Alcian blue staining before Nb infection, but they expressed very low levels of beta-subunit as assessed by immunohistochemical staining. These levels were increased by day 11 postinfection and reached a maximum at day 14. Since serum IgE levels correlated well with the degree of beta-subunit expression, we investigated whether the observed enhancement of receptor expression might occur through the stabilization of receptor complexes by IgE. Therefore, Lewis rats were treated with myeloma IgE, and beta-subunit expression was examined. In both tongue and jejunal tissue, a significant rise in beta-subunit expression was observed in response to IgE injection, although levels of beta-subunit expression were not as high as those observed in Nb-infected animals. The increase in beta-subunit expression was accompanied by an increase in the amount of mast cell-associated IgE. These observations may have important implications for the regulation of IgE receptor expression during disease. C1 MCMASTER UNIV,HLTH SCI CTR,DEPT PATHOL,MOL IMMUNOL VIROL & INFLAMMAT PROGRAM,HAMILTON,ON L8N 3Z5,CANADA. MCMASTER UNIV,HLTH SCI CTR,DEPT ANAT PATHOL,HAMILTON,ON L8N 3Z5,CANADA. NIAMSD,SECT CHEM IMMUNOL,NIH,BETHESDA,MD. NR 31 TC 31 Z9 31 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 APR 15 PY 1997 VL 158 IS 8 BP 3805 EP 3812 PG 8 WC Immunology SC Immunology GA WT196 UT WOS:A1997WT19600034 PM 9103447 ER PT J AU Wu, XB Dolecki, GJ Sherry, B Zagorski, J Lefkowith, JB AF Wu, XB Dolecki, GJ Sherry, B Zagorski, J Lefkowith, JB TI Chemokines are expressed in a myeloid cell-dependent fashion and mediate distinct functions in immune complex glomerulonephritis in rat SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; COLONY-STIMULATING FACTOR; ANTIBODY; CYTOKINES; NEUTROPHIL; LEUKOCYTES; CLONING; PROTEIN; FAMILY; GENE AB Using anti-glomerular basement membrane nephritis in rats, we investigated the mechanisms underlying in situ chemokine expression and the in vivo function of these cytokines during the acute phase of this model. We observed that CXC chemokine expression was monophasic and paralleled neutrophil (PMN) influx, whereas CC chemokine expression was biphasic with peaks coinciding with the influx of PMNs and macrophages (M phi). The initial peak of chemokine expression was attenuated by decomplementation, neutropenia, and leukopenia, while the latter peak was attenuated only by leukopenia and augmented in the accelerated form of this disease model, corresponding to an increase in M phi influx. Differential expression of chemokines by PMNs and M phi was not an intrinsic property of these cells, as these leukocytes expressed similar profiles of chemokines in vitro. Immunostaining for M phi inflammatory protein-1 alpha, a CC chemokine, in acute nephritis validated that expression during acute nephritis was accompanied by local protein production. Moreover, neutralizing Ab to M phi inflammatory protein-1 alpha attenuated the acute phase proteinuria, but not the accompanying influx of PMNs. Neutralizing Ab to cytokine-induced neutrophil chemoattractant (a CXC chemokine), in comparison, inhibited both PMN influx and proteinuria. A combination of both Abs was not significantly more effective than either alone. In sum, the influx of myeloid cells is necessary for local chemokine expression in anti-glomerular basement membrane nephritis, although the differential expression of CXC and CC chemokines must involve additional factors. CXC and CC chemokines also mediate distinct, but overlapping, pathophysiologic roles in the acute phase of this model. C1 WASHINGTON UNIV,SCH MED,DEPT MED,DIV RHEUMATOL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT MOL BIOL & PHARMACOL,ST LOUIS,MO 63110. PICOWER INST MED RES,MANHASSET,NY 11030. NIH,BETHESDA,MD 20892. FU NIAMS NIH HHS [AR-07279] NR 38 TC 41 Z9 45 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 APR 15 PY 1997 VL 158 IS 8 BP 3917 EP 3924 PG 8 WC Immunology SC Immunology GA WT196 UT WOS:A1997WT19600049 PM 9103462 ER PT J AU Ahlers, JD Dunlop, N Alling, DW Nara, PL Berzofsky, JA AF Ahlers, JD Dunlop, N Alling, DW Nara, PL Berzofsky, JA TI Cytokine-in-adjuvant steering of the immune response phenotype to HIV-1 vaccine constructs - Granulocyte-macrophage colony-stimulating factor and TNF-alpha synergize with IL-12 to enhance induction of cytotoxic T lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; GROWTH-FACTOR-BETA; IFN-GAMMA; INTERFERON-GAMMA; EXPERIMENTAL LEISHMANIASIS; NEUTRALIZING ANTIBODY; ANTIGEN-PRESENTATION; PEPTIDE VACCINATION; ANTITUMOR IMMUNITY; TH1 CELLS AB To enhance and steer immune responses to synthetic peptide vaccines toward selected functional types and to understand the cooperative action of cytokines in fine-tuning the immune response, we attempted to influence the in vivo cytokine environment by delivering cytokines directly to the microenvironment in which the immune response is initiated. Here we study the effects of IL-2, IL-4, IL-7, IL-1 beta, IL-12, IFN-gamma, TNF-alpha, and granulocyte-macrophage CSF (GM-CSF) incorporated with peptide in adjuvant on a variety of responses elicited: CTL, T cell proliferation, cytokine production and message, and Ab isotype. We show GM-CSF to be the single most effective cytokine for enhancing both cellular and humoral immunity to two previously characterized HIV-1 MN vaccine constructs. Novel synergies were also detected. GM-CSF synergized with IL-12 for CTL induction in BALB/c mice concomitant with suppression of Th2 cytokines IL-4 and IL-10. TNF-alpha also synergized with IL-12, but by a different mechanism, inducing IFN-gamma production in BALB/c mice and thus shifting the response to a Th1 phenotype. The results presented here suggest that in addition to IL-2, optimum induction of CD8(+) CTL in vivo requires a combination of cytokines, including GM-CSF (probably acting to enhance Ag presentation and CD4(+) cell help) and IL-12 (steering the Th response toward Th1 cytokines). C1 NCI,MOL IMMUNOGENET & VACCINE RES SECT,METAB BRANCH,NIH,BETHESDA,MD 20892. NCI,VACCINE RESISTANT DIS SECT,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NIAID,OFF SCI DIRECTOR,NIH,BETHESDA,MD 20892. NR 80 TC 130 Z9 133 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 APR 15 PY 1997 VL 158 IS 8 BP 3947 EP 3958 PG 12 WC Immunology SC Immunology GA WT196 UT WOS:A1997WT19600052 PM 9103465 ER PT J AU Kuhns, DB Priel, DAL Gallin, JI AF Kuhns, DB Priel, DAL Gallin, JI TI Endotoxin and IL-1 hyporesponsiveness in a patient with recurrent bacterial infections SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LIPOPOLYSACCHARIDE; NEUTROPHILS; MACROPHAGES; MONOCYTES; SELECTIN; CERAMIDE; KINASE; CELLS AB We describe a 15-yr-old girl with recurrent bacterial infections who is refractory to the effects of LPS in vivo and in vitro and IL-1 in vitro. Intravenous challenge of the patient with Escherichia coli endotoxin caused a subnormal febrile response, little alteration in the number of circulating neutrophils, and subnormal elevations in the plasma levels of TNF-alpha, IL-6, IL-8, lactoferrin, and granulocyte CSF; however, normal levels of the anti-inflammatory mediators IL-1 receptor antagonist and soluble TNF receptor (60 kDa) were induced. Studies in vitro indicated the patient's monocytes expressed CD14, the LPS receptor, and bound LPS in a specific manner, but failed to produce TNF-alpha and granulocyte CSF after stimulation with LPS, and failed to respond to IL-1, heat-killed Staphylococcos aureus, and soluble glucan. Peripheral blood patient neutrophils exhibited normal expression of CD14, but failed to respond to treatment with LPS (100-1000 ng/ml for 30 min at 37 degrees C), a treatment that caused increased expression of the surface markers, C10, CD18, CD11b, CD67, and CD45, and decreased expression of L-selectin in normal neutrophils. Treatment of normal and patient neutrophils with FMLP (0.1 mu M) resulted in equivalent altered expression of these surface markers. Patient neutrophils could not be primed by either LPS or IL-1 beta for enhanced FMLP-induced O-2(-) generation, but primed normally to TNF-alpha and platelet-activating factor. This patient's hyporesponsiveness to LPS and IL-1 is most likely due to a defect very early in the signal-transduction pathway. C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. FREDERICK CANC RES & DEV CTR,SAIC,FREDERICK,MD 21702. NR 14 TC 80 Z9 82 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 APR 15 PY 1997 VL 158 IS 8 BP 3959 EP 3964 PG 6 WC Immunology SC Immunology GA WT196 UT WOS:A1997WT19600053 PM 9103466 ER PT J AU Knutson, P Ghiani, CA Zhou, JM Gallo, V McBain, CJ AF Knutson, P Ghiani, CA Zhou, JM Gallo, V McBain, CJ TI K+ channel expression and cell proliferation are regulated by intracellular sodium and membrane depolarization in oligodendrocyte progenitor cells SO JOURNAL OF NEUROSCIENCE LA English DT Article DE potassium channels; O-2A progenitors; cell proliferation; glial development; depolarization; lineage progression ID CENTRAL NERVOUS-SYSTEM; KAINATE RECEPTOR ACTIVATION; PRECURSOR CELLS; GROWTH-FACTOR; EXTRACELLULAR POTASSIUM; RETINOIC ACID; SPINAL-CORD; PATCH-CLAMP; CULTURED ASTROCYTES; GLIAL PROGENITORS AB The effects of a variety of antiproliferative agents on voltage-dependent K+ channel function in cortical oligodendrocyte progenitor (O-2A) cells were studied. Previously, we had shown that glutamate receptor activation reversibly inhibited O-2A cell proliferation stimulated by mitogenic factors and prevented lineage progression by attenuating outward K+ currents in O-2A cells. We now show that the antiproliferative actions of glutamate receptor activation are Ca2+-independent and arise from an increase in intracellular Nat and subsequent block of outward Kt currents. In support of this mechanism, agents that acted to depolarize O-2A cells or increase intracellular sodium similarly had an antiproliferative effect, attributable at least in part to a reduction in voltage-gated K+ currents. Also, these effects were reversible and Ca2+-independent. Chronic treatment with glutamate agonists was without any long-term effect on K+ current function. Cells cultured in elevated K+, however, demonstrated an upregulation of inward rectifier K+ currents, concomitant with an hyperpolarization of the resting membrane potential. This culture condition therefore promoted a current phenotype typical of pro-oligodendroblasts. Finally, cells chronically treated with the mitotic inhibitor retinoic acid displayed a selective downregulation of outward K+ currents. In conclusion, signals that affect O-2A cell proliferation do so by regulating K+ channel function. These data indicate that the regulation of K+ currents in cells of the oligodendrocyte lineage plays an important role in determining their proliferative potential and demonstrate that O-2A cell K+ current phenotype can be modified by long-term depolarization of the cell membrane. C1 NICHHD,LAB CELLULAR & MOL NEUROPHYSIOL,NIH,BETHESDA,MD 20892. OI Ghiani, Cristina/0000-0002-9867-6185 NR 55 TC 113 Z9 113 U1 1 U2 4 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 APR 15 PY 1997 VL 17 IS 8 BP 2669 EP 2682 PG 14 WC Neurosciences SC Neurosciences & Neurology GA WX903 UT WOS:A1997WX90300003 PM 9092588 ER PT J AU Hommer, D Andreasen, P Rio, D Williams, W Ruttimann, U Momenan, R Zametkin, A Rawlings, R Linnoila, M AF Hommer, D Andreasen, P Rio, D Williams, W Ruttimann, U Momenan, R Zametkin, A Rawlings, R Linnoila, M TI Effects of m-chlorophenylpiperazine on regional brain glucose utilization: A positron emission tomographic comparison of alcoholic and control subjects SO JOURNAL OF NEUROSCIENCE LA English DT Article DE alcoholism; serotonin; PET; m-chlorophenylpiperazine; striatum; thalamus; orbital cortex; frontal cortex ID LINKING BASAL GANGLIA; META-CHLOROPHENYLPIPERAZINE; PARKINSONS-DISEASE; MESSENGER-RNAS; SEROTONIN; ALEXITHYMIA; METABOLISM; RESPONSES; RECEPTORS; CORTEX AB m-Chlorophenylpiperazine (mCPP) is a mixed serotonin agonist/antagonist used extensively in psychiatric research. Alcoholics show blunted neuroendocrine responses to mCPP, and in some settings mCPP can induce craving for alcohol, particularly among early onset alcoholics. We used 2-[F-18]-2-deoxy-D-glucose positron emission tomography to examine the effects of intravenously administered mCPP (0.08 mg/kg) on brain glucose utilization in a group of 18 male alcoholics and 12 healthy male control subjects. Differences between two sequential scans (the first followed placebo and the second followed mCPP) were evaluated statistically with a Gaussian random field-based method, Among healthy volunteers mCPP significantly increased brain glucose metabolism in the right medial and posterior orbital gyrus, the cerebellar hemispheres bilaterally, the left nucleus accumbens, the head of the caudate nucleus bilaterally, the anterior and medial-dorsal nuclei of the thalamus bilaterally, the middle frontal gyrus, the left insular cortex, the left middle temporal gyrus, and the posterior cingulate gyrus. Among alcoholic subjects mCPP significantly increased brain glucose metabolism in larger areas of the cerebellum and posterior cingulate than it did in healthy volunteers, but compared with the healthy volunteers, alcoholics showed a smaller area of mCPP-induced activation in the thalamus, almost no activation in the orbital cortices, and no activation at all in the head of the caudate nucleus or the middle frontal gyrus. These results suggest that a serotoninergic challenge activates basal ganglia circuits involving orbital and prefrontal cortices among healthy volunteers but that the response of these circuits is blunted among alcoholics. C1 NIMH,CHILD PSYCHIAT BRANCH,NIH,BETHESDA,MD 20892. RP Hommer, D (reprint author), NIAAA,CLIN STUDIES LAB,DIV INTRAMURAL CLIN & BIOL RES,NIH,BLDG 10,ROOM 3C102,10 CTR DR,BETHESDA,MD 20892, USA. NR 44 TC 51 Z9 53 U1 1 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 15 PY 1997 VL 17 IS 8 BP 2796 EP 2806 PG 11 WC Neurosciences SC Neurosciences & Neurology GA WX903 UT WOS:A1997WX90300016 PM 9092601 ER PT J AU Duffy, CJ Wurtz, RH AF Duffy, CJ Wurtz, RH TI Medial superior temporal area neurons respond to speed patterns in optic flow SO JOURNAL OF NEUROSCIENCE LA English DT Article DE optic flow motion; speed; vision; extrastriate; MST ID MACAQUE MONKEY; MST NEURONS; EXPANSION CONTRACTION; DEPTH-PERCEPTION; ROTATION CELLS; FIELD STIMULI; DORSAL PART; MOTION; SELECTIVITY; SENSITIVITY AB The speed of visual motion in optic flow fields can provide important cues about self-movement. We have studied the speed sensitivities of 131 neurons in the dorsal region of the medial superior temporal area (MSTd) that responded to either radial or circular optic flow stimuli. The responses of more than two-thirds of these neurons were strongly modulated by changes in the mean speed of motion in optic flow stimuli, with response profiles resembling simple filter characteristics. When we removed the normal gradient of speeds in optic flow (slower speeds in the center, faster speeds in the periphery), approximately two-thirds of the neurons showed changes in their responses. When the speed gradient was altered rather than eliminated, almost nine in 10 neurons preferred either a normal speed gradient or an inverted one (slower speeds near the periphery) over stimuli with no speed gradient. These speed gradient preferences do not come simply from different speed preferences in the central and peripheral segments of the stimulus area. Rather, these speed gradient preferences seemed to reflect interactions between simultaneously presented speeds within an optic flow stimulus. The sensitivity of MSTd neurons to patterns of speed, as well as patterns of direction, strengthens the view that these neurons are well suited to the analysis of optic flow. Sensitivity to speed gradients in optic flow might contribute to neuronal mechanisms for spatial orientation during self-movement and for representing the three-dimensional structure of the visual environment. C1 UNIV ROCHESTER, MED CTR, DEPT ANAT & NEUROBIOL, ROCHESTER, NY 14642 USA. UNIV ROCHESTER, MED CTR, DEPT OPHTHALMOL, ROCHESTER, NY 14642 USA. UNIV ROCHESTER, MED CTR, DEPT BRAIN & COGNIT SCI, ROCHESTER, NY 14642 USA. UNIV ROCHESTER, MED CTR, CTR VISUAL SCI, ROCHESTER, NY 14642 USA. NEI, SENSORIMOTOR RES LAB, NIH, BETHESDA, MD 20892 USA. RP Duffy, CJ (reprint author), UNIV ROCHESTER, MED CTR, DEPT NEUROL, 601 ELMWOOD AVE, BOX 673, ROCHESTER, NY 14642 USA. FU NEI NIH HHS [R01-EY10287] NR 29 TC 107 Z9 108 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 15 PY 1997 VL 17 IS 8 BP 2839 EP 2851 PG 13 WC Neurosciences SC Neurosciences & Neurology GA WX903 UT WOS:A1997WX90300020 PM 9092605 ER PT J AU Xiao, RP Valdivia, HH Bogdanov, K Valdivia, C Lakatta, EG Cheng, HP AF Xiao, RP Valdivia, HH Bogdanov, K Valdivia, C Lakatta, EG Cheng, HP TI The immunophilin FK506-binding protein modulates Ca2+ release channel closure in rat heart SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID CARDIAC RYANODINE RECEPTORS; FK-506 BINDING-PROTEIN; SARCOPLASMIC-RETICULUM; CALCIUM-RELEASE; SKELETAL-MUSCLE; SPATIAL NONUNIFORMITIES; ELEMENTARY EVENTS; CONTROL MECHANISM; CONTRACTION; MYOCYTES AB 1. The nature of the signal that terminates the release of Ca2+ from the cardiac sarcoplasmic reticulum has remained elusive. This study was intended to examine whether FK506-binding protein (FKBP), which is tightly associated to the ryanodine receptor (RyR)/Ca2+ release channel, plays a role in the termination of Ca2+-induced Ca2+ release (CICR) in heart. 2. Confocal microscopy and the Ca2+ indicator fluo-3 were used to visualize the elementary release events, i.e. 'Ca2+ sparks' in rat ventricular myocytes under resting or voltage-clamped conditions. additionally, electrophysiological single-channel recordings, at constant [Ca2+] or during [Ca2+] steps produced by photorelease of caged Ca2+, were obtained from rat cardiac RyRs incorporated in planar lipid bilayers. 3. Inhibition of FKBP by the immunosuppressants FK506 or rapamycin increased the duration of spontaneous or depolarization-evoked Ca2+ sparks 6- to 7-fold. In addition, Ca2+ sparks were seen with two-level amplitudes, corresponding to full and half normal spark amplitude. 4. FK506 potentiated and prolonged electrically stimulated [Ca2+](i) transients and contractions, but did not affect the amplitude and kinetics of the L-type Ca2+ channel current. 5. In planar lipid bilayers, FK506 (15 mu M) prolonged similar to 7-fold the mean open lifetime of reconstituted single RyRs, induced the appearance of long-lasting subconductance states, and markedly slowed the spontaneous decay of RyR activity elicited by fast and sustained Ca2+ stimuli. The time constant of the spontaneous decay of activity increased from 1.8 s in control to greater than or equal to 20 s in the presence of FK506. 6. We conclude that FKBP may afford an intrinsic mechanism to terminate RyR openings and it may thus exert a negative feedback on CICR in heart cells. C1 UNIV WISCONSIN,SCH MED,DEPT PHYSIOL,MADISON,WI 53706. RP Xiao, RP (reprint author), NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,NIH,BALTIMORE,MD 21224, USA. FU NHLBI NIH HHS [HL55438] NR 38 TC 150 Z9 152 U1 0 U2 4 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 APR 15 PY 1997 VL 500 IS 2 BP 343 EP 354 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA WW836 UT WOS:A1997WW83600008 PM 9147322 ER PT J AU Wolfsberg, TG Landsman, D AF Wolfsberg, TG Landsman, D TI A comparison of expressed sequence tags (ESTs) to human genomic sequences SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENE DISCOVERY; DBEST; TOOL AB The Expressed Sequence Tag (EST) division of GenBank, dbEST, is a large repository of the data being generated by human genome sequencing centers. ESTs are short, single pass cDNA sequences generated from randomly selected library clones. The similar to 415 000 human ESTs represent a valuable, law priced, and easily accessible biological reagent. As many ESTs are derived from yet uncharacterized genes, dbEST is a prime starting point for the identification of novel mRNAs. Conversely other genes are represented by hundreds of ESTs, a redundancy which may provide data about rare mRNA isoforms. Here we present an analysis of >1000 ESTs generated by the WashU-Merck EST project. These ESTs were collected by querying dbEST with the genomic sequences of 15 human genes. When we aligned the matching ESTs to the genomic sequences, we found that in one gene, 73% of the ESTs which derive from spliced or partially spliced transcripts either contain intron sequences or are spliced at previously unreported sites; other genes have lower percentages of such ESTs, and some have none. This finding suggests that ESTs could provide researchers with novel information about alternative splicing in certain genes. In a related analysis of pairs of ESTs which are reported to derive from a single gene, we found that as many as 26% of the pairs do not BOTH align with the sequence of the same gene. We suspect that some of these unusual ESTs result from artifacts in EST generation, and caution researchers that they may find such clones while analyzing sequences in dbEST. C1 NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. RI Landsman, David/C-5923-2009; OI Landsman, David/0000-0002-9819-6675 NR 20 TC 105 Z9 111 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR 15 PY 1997 VL 25 IS 8 BP 1626 EP 1632 DI 10.1093/nar/25.8.1626 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WV078 UT WOS:A1997WV07800023 PM 9092672 ER PT J AU Hsu, YT Wolter, KG Youle, RJ AF Hsu, YT Wolter, KG Youle, RJ TI Cytosol-to-membrane redistribution of Bax and Bcl-X-L during apoptosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE programmed cell death; Bcl-2; Bax; diphtheria toxin ID PROGRAMMED CELL-DEATH; DIPHTHERIA-TOXIN; PROTEIN; ASSOCIATION; BCL-X(L); PRODUCT; GENE; RNA AB Bcl-2, Bcl-X-L, and fax are members of the Bcl-2 family that play key roles in the regulation of apoptosis. These proteins are believed to be membrane bound and their ability to undergo both homodimerization and heterodimerization has been proposed to regulate apoptosis. Herein we report that in murine thymocytes, Bcl-2 is exclusively membrane-bound, whereas Bax is present predominantly in the cytosol and Bcl-X-L is present in both soluble and membrane-bound forms. Induction of apoptosis in murine thymocytes by dexamethasone or gamma-irradiation shifts the subcellular locations of Bax and Bcl-X-L from soluble to membrane-bound forms. A similar shift in the localization of Bax from the cytosol to membranes was observed in HL-60 leukemia cells upon induction of apoptosis by staurosporine. Inhibition of apoptosis with cycloheximide inhibits the movement of Bax and Bcl-X-L in thymocytes from the cytosol into membranes induced by dexamethasone treatment. These movements may represent an important step in the pathway by which members of this family regulate apoptosis. RP Hsu, YT (reprint author), NINCDS, BIOCHEM SECT,SURG NEUROL BRANCH,NIH,10 CTR DR, ROOM 5D-37, BETHESDA, MD 20892 USA. NR 27 TC 890 Z9 904 U1 3 U2 17 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 15 PY 1997 VL 94 IS 8 BP 3668 EP 3672 DI 10.1073/pnas.94.8.3668 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WW810 UT WOS:A1997WW81000036 PM 9108035 ER PT J AU Saitoh, H Pu, R Cavenagh, M Dasso, M AF Saitoh, H Pu, R Cavenagh, M Dasso, M TI RanBP2 associates with Ubc9p and a modified form of RanGAP1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DNA-REPLICATION; CYCLIN-B; PROTEIN; UBIQUITIN; MITOSIS; ACTIVATION; TRANSPORT; COMPLEX; GTPASE; IMPORT AB Ran is a small GTPase required for nuclear transport in eukaryotic cells [Gorlich, D. & Mattaj, I. W. (1996) Science 271, 1513-1518]. Mutants in Ran also show defects in mRNA processing, cell cycle regulation, and other aspects of nuclear function [Rush, M. G., Drivas, G. & D'Eustachio, P. (1996) BioEssays 18, 103-112; Sazer, S. (1996) Trends Cell Biol. 6, 81-85]. In an effort to understand the role of Ran in these diverse processes, we previously characterized 10 Ran interacting proteins (Rips) from Xenopus egg extracts. In this report, we present further characterization of a complex containing three of these Rips: p340(RanBP2), p88, and p18. We have cloned the Xenopus homologue of RanGAP1, and we show here that p88 is a modified form of this protein. In RanGAP assays, the p340(RanBP2)-p88-p18 complex contains GTPase-activating protein activity, indicating that RanGAP1 is not inactivated by modification. Rather, modification of RanGAP1 appears to be linked to its association with p340(RanBP2) because we did not observe unmodified RanGAP1 in p340(RanBP2) immunoprecipitates. We have also characterized p18, and we found that it is the Xenopus homologue of Ubc9p, an E2 ubiquitin-conjugating enzyme that is required for cell cycle regulation [Seufert, W., Futcher, B. & Jentsch, S. (1995) Nature (London) 373, 78-81]. Using antibodies directed against Xenopus Ubc9p, we have confirmed that Ubc9p associates with p340(RanBP2) in Xenopus extracts. These results suggest Ubc9p's role in cell cycle regulation may involve either modification of nuclear transport substrates or the nuclear transport machinery. C1 NICHHD,MOL EMBRYOL LAB,NIH,BETHESDA,MD 20892. NR 30 TC 151 Z9 154 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 15 PY 1997 VL 94 IS 8 BP 3736 EP 3741 DI 10.1073/pnas.94.8.3736 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WW810 UT WOS:A1997WW81000048 PM 9108047 ER PT J AU Eglitis, MA Mezey, E AF Eglitis, MA Mezey, E TI Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gene transfer; bone marrow transplantation; stem cells; lineage analysis ID MEDIATED GENE-TRANSFER; NERVOUS-SYSTEM; MOUSE-BRAIN; STEM-CELLS; EXPRESSION AB Glial cells are thought to derive embryologically from either myeloid cells of the hematopoietic system (microglia) or neuroepithelial progenitor cells (astroglia and oligodendrocytes). How ever, it is unclear whether the glia in adult brains free of disease or injury originate solely from cells present in the brain since the fetal stage of development, or if there is further input into such adult brains from cells originating outside the central nervous system. To test the ability of hematopoietic cells to contribute to the central nervous system, we have transplanted adult female mice with donor bone marrow cells genetically marked either with a retroviral tag or by using male donor cells. Using in situ hybridization histochemistry, a continuing influx of hematopoietic cells into the brain was detected. Marrow-derived cells were already detected in the brains of mice 3 days after transplant, and their numbers increased over the next several weeks, exceeding 14,000 cells per brain in several animals. Marrow-derived cells were widely distributed throughout the brain, including the cortex, hippocampus, thalamus, brain stem, and cerebellum. When in situ hybridization histochemistry was combined with immunohistochemical staining using lineage-specific markers, some bone marrow derived cells were positive for the microglial antigenic marker F4/80. Other marrow-derived cells surprisingly expressed the astroglial marker glial fibrillary acidic protein. These results indicate that some microglia and astroglia arise from a precursor that is a normal constituent of adult bone marrow. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NINCDS,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NR 36 TC 763 Z9 846 U1 0 U2 16 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 15 PY 1997 VL 94 IS 8 BP 4080 EP 4085 DI 10.1073/pnas.94.8.4080 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WW810 UT WOS:A1997WW81000109 PM 9108108 ER PT J AU Schafer, MKH Schutz, B Weihe, E Eiden, LE AF Schafer, MKH Schutz, B Weihe, E Eiden, LE TI Target-independent cholinergic differentiation in the rat sympathetic nervous system SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE autonomic nervous system development; tyrosine hydroxylase; vesicular acetylcholine transporter; vesicular monoamine transporter ID VESICULAR ACETYLCHOLINE TRANSPORTER; NEUROTRANSMITTER PLASTICITY; NEURONS; EXPRESSION; LOCALIZATION AB Chemical coding in the sympathetic nervous system involves both noradrenergic and, for a minority of neurons, cholinergic neurotransmission. The expression of the cholinergic phenotype in the developing sympathetic nervous system was examined to determine if coding for cholinergic transmission occurs before or after innervation of peripheral target organs. The vesicular acetylcholine transporter (VAChT) and choline acetyltransferase, the products of the ''cholinergic gene locus'' determining the cholinergic phenotype, were expressed in principal cells of the paravertebral, but only rarely in prevertebral, sympathetic chains as early as embryonic day 14. A subpopulation of VAChT- and choline acetyltransferase-positive sympathetic ganglion cells persisted throughout development of the stellate and more caudal paravertebral ganglia into anatomically distinct cell groups, and into adulthood. The forepaw eccrine sweat glands, innervated exclusively by the stellate ganglion, received VAChT-positive nerve terminals at least as early as postembryonic day 4, coincident with the development of the sweat glands themselves. These terminals, like the VAChT-positive cell bodies of the developing stellate ganglion, have some noradrenergic traits including expression of tyrosine hydroxylase, but did not express the vesicular monoamine transporter, and are therefore not functionally noradrenergic. Development of the cholinergic phenotype in principal cells of the sympathetic paravertebral ganglia apparently occurs via receipt of instructive cues, or selection, within the sympathetic chain itself or perhaps even during migration of the cells of the neural crest from which the paravertebral ganglia arise. C1 NIMH,MOL NEUROSCI SECT,LAB CELLULAR & MOL REGULAT,BETHESDA,MD 20892. UNIV MARBURG,DEPT ANAT & CELL BIOL,D-35037 MARBURG,GERMANY. OI Eiden, Lee/0000-0001-7524-944X NR 21 TC 56 Z9 60 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 15 PY 1997 VL 94 IS 8 BP 4149 EP 4154 DI 10.1073/pnas.94.8.4149 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WW810 UT WOS:A1997WW81000121 PM 9108120 ER PT J AU Rondinone, CM Wang, LM Lonnroth, P Wesslau, C Pierce, JH Smith, U AF Rondinone, CM Wang, LM Lonnroth, P Wesslau, C Pierce, JH Smith, U TI Insulin receptor substrate (IRS) 1 is reduced and IRS-2 is the main docking protein for phosphatidylinositol 3-kinase in adipocytes from subjects with non-insulin-dependent diabetes mellitus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SRC HOMOLOGY-2 DOMAINS; RAT ADIPOSE-CELLS; GLUCOSE-TRANSPORT; 1-PHOSPHATIDYLINOSITOL 3-KINASE; TYROSINE PHOSPHORYLATION; SIGNALING SYSTEM; PLASMA-MEMBRANE; INTACT-CELLS; TRANSLOCATION; ACTIVATION AB The large docking protein IRS-1 is a major substrate for the insulin receptor and other tyrosine kinases. It plays a key role in eliciting many of insulin's actions, including binding and activation of phosphatidylinositol (PI) 3-kinase and the subsequent increase in glucose transport. Gene disruption of IRS-1 in mice is associated with an impaired insulin-stimulated glucose disposal in vivo and glucose transport in vitro, but the survival of the animals and residual insulin sensitivity is dependent on the presence of the alternative docking protein IRS-2. We examined the expression and function of IRS-1 and IRS-2 in adipocytes from healthy and diabetic individuals. Cells from subjects with non-insulin-dependent diabetes mellitus (NIDDM), but not with insulin dependent diabetes mellitus, had an impaired insulin effect and a marked reduction (70 +/- 6%) in the expression of IRS-1 protein, whereas IRS-2 was unchanged. In normal cells, IRS-1 was the main docking protein for the binding and activation of insulin-stimulated PI 3-kinase; IRS-2 was also functional but required a higher insulin concentration for a similar binding and activation of PI 3-kinase. In contrast in NIDDM cells with a low IRS-1 content, IRS-2 became the main docking protein. These findings may provide important reasons for the insulin resistance in NIDDM. C1 NCI, CELLULAR & MOL BIOL LAB, NATL INST HLTH, BETHESDA, MD 20892 USA. RP Rondinone, CM (reprint author), GOTHENBURG UNIV, SAHLGRENSKA UNIV HOSP, LUNDBERG LAB DIABET RES, S-41345 GOTHENBURG, SWEDEN. NR 35 TC 185 Z9 199 U1 0 U2 6 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 APR 15 PY 1997 VL 94 IS 8 BP 4171 EP 4175 DI 10.1073/pnas.94.8.4171 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WW810 UT WOS:A1997WW81000125 PM 9108124 ER PT J AU Fay, MP Feuer, EJ AF Fay, MP Feuer, EJ TI Confidence intervals for directly standardized rates: A method based on the gamma distribution SO STATISTICS IN MEDICINE LA English DT Article AB We offer an approximation to central confidence intervals for directly standardized rates, where we assume that the rates are distributed as a weighted sum of independent Poisson random variables. Like a recent method proposed by Dobson, Kuulasmaa, Eberle and Scherer, our method gives exact intervals whenever the standard population is proportional to the study population. In cases where the two populations differ non-proportionally, we show through simulation that our method is conservative while other methods (the Dobson et al. method and the approximate bootstrap confidence method) can be liberal. (C) 1997 by John Wiley & Sons, Ltd. RP Fay, MP (reprint author), NCI,DIV CANC PREVENT & CONTROL,EXECUT PLAZA N,SUITE 344,6130 EXECUT BLVD MSC 735,BETHESDA,MD 20892, USA. RI Fay, Michael/A-2974-2008; OI Fay, Michael P./0000-0002-8643-9625 NR 19 TC 254 Z9 257 U1 2 U2 7 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 APR 15 PY 1997 VL 16 IS 7 BP 791 EP 801 PG 11 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 WU162 UT WOS:A1997WU16200007 PM 9131766 ER PT J AU Glowa, JR Fantegrossi, WE AF Glowa, JR Fantegrossi, WE TI Effects of dopaminergic drugs on food- and cocaine-maintained responding .4. Continuous cocaine infusions SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE cocaine; self-administration; replacement substitution therapy; drug reinforcement; agonists; rhesus monkeys ID RHESUS-MONKEYS; BEHAVIOR; SCHEDULES; AGONIST AB The effects of cocaine (continuously infused during the session with and without a pre-loading dose) on responding maintained under multiple fixed-ratio 30 schedules of limited access to food and cocaine delivery (10 or 56 mu g/kg per injection) were studied in nine rhesus monkeys. When responding was maintained by 10 mu g/kg per injection, cocaine decreased rates of cocaine-maintained responding in a dose-related manner while having no effect on food-maintained responding. When responding was maintained by 56 mu g/kg per injection, cocaine decreased both cocaine- and food-maintained responding. These results show that the effects of continuous infusions of cocaine depend upon both the unit dose of cocaine and the event that maintains responding. As such, the effects of continuous infusions of cocaine are similar to those of other, longer-acting dopamine agonists. Such results support the development of long-acting agonist approaches to the pharmacotherapeutic treatment of cocaine abuse. (C) 1997 Elsevier Science Ireland Ltd. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT PSYCHIAT,BETHESDA,MD 20814. NIDDK,MED CHEM LAB,NIH,BETHESDA,MD 20892. FU NIDA NIH HHS [DA 09820]; ONDIEH CDC HHS [RA-ND-94-24] NR 24 TC 22 Z9 22 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD APR 14 PY 1997 VL 45 IS 1-2 BP 71 EP 79 DI 10.1016/S0376-8716(97)01350-1 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA XA326 UT WOS:A1997XA32600009 PM 9179509 ER PT J AU Svikis, DS Golden, AS Huggins, GR Pickens, RW McCaul, ME Velez, ML Rosendale, CT Brooner, RK Gazaway, PM Stitzer, ML Ball, CE AF Svikis, DS Golden, AS Huggins, GR Pickens, RW McCaul, ME Velez, ML Rosendale, CT Brooner, RK Gazaway, PM Stitzer, ML Ball, CE TI Cost-effectiveness of treatment for drug-abusing pregnant women SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE pregnancy; drug dependence; treatment; cost-effectiveness; outcome ID ALCOHOLISM-TREATMENT; SUBSTANCE-ABUSE; COCAINE AB Neonatal intensive care unit (NICU) and drug treatment costs were compared in two groups of pregnant drug abusing women: 100 admissions to a multidisciplinary treatment program and active in care at the time of delivery and 46 controls not entering drug treatment. Clinical measures included urine toxicology at delivery, infant birthweight, Apgar scores and need for and duration of NICU services. Cost measures included drug treatment and NICU costs. Treatment patients showed better clinical outcome at delivery, with less drug use and higher infant estimated gestational age, birthweight and Apgar scores. Infants of treatment patients were also less likely to require NICU services and, for those that did: had a shorter stay. When total cost was examined (including drug treatment), mean net savings for treatment subjects was $4644 per mother/infant pair. The study demonstrates the cost-effectiveness of treatment for pregnant drug abusing women, with savings in NICU costs exceeding costs of drug treatment. (C) 1997 Elsevier Science Ireland Ltd. C1 NIDA, BALTIMORE, MD 21224 USA. MARYLAND STATE ALCOHOL & DRUG ABUSE ADM, BALTIMORE, MD 21224 USA. JOHNS HOPKINS BAYVIEW MED CTR, BALTIMORE, MD 21224 USA. RP Svikis, DS (reprint author), JOHNS HOPKINS UNIV, SCH MED, 4940 EASTERN AVE, BALTIMORE, MD 21224 USA. FU NIDA NIH HHS [P5O DA 09258] NR 33 TC 61 Z9 61 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD APR 14 PY 1997 VL 45 IS 1-2 BP 105 EP 113 DI 10.1016/S0376-8716(97)01352-5 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA XA326 UT WOS:A1997XA32600012 PM 9179512 ER PT J AU Yoo, SH Kang, YK AF Yoo, SH Kang, YK TI Identification of the secretory vesicle membrane binding region of chromogranin B SO FEBS LETTERS LA English DT Article DE sequence; chromogranin B; pH; secretory vesicle membrane ID MESSENGER-RNA; CDNA SEQUENCE; PANCREASTATIN; PRECURSOR; PROTEINS; GENE AB In the past a synthetic peptide representing the conserved near N-terminal region of chromogranin B (CGB) (residues 17-36) has been shown to interact with the vesicle membrane, Hence, it was necessary to confirm this observation with CGB deletion proteins, In order to address this need and to confirm the published sequence of CGB, we cloned a CGB gene and produced various CGB deletion proteins, The recombinant CGB protein lacking the first 15 (rCGB 16-626) or 16 amino acid residues (rCGB 17-626) bound to the vesicle membrane as well as the full-length CGB, However, rCGB 49-626, lacking the conserved near N-terminal region, failed to interact with the vesicle membrane, indicating an anchor role for the conserved near the N-terminal region. (C) 1997 Federation of European Biochemical Societies. RP Yoo, SH (reprint author), NIDCD,NEUROCHEM LAB,NIH,5 RES COURT,2A37,BETHESDA,MD 20892, USA. NR 17 TC 25 Z9 27 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 APR 14 PY 1997 VL 406 IS 3 BP 259 EP 262 DI 10.1016/S0014-5793(97)00276-7 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA WV198 UT WOS:A1997WV19800006 PM 9136897 ER PT J AU Wachsman, JT AF Wachsman, JT TI DNA methylation and the association between genetic and epigenetic changes: Relation to carcinogenesis SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Review DE author; please supply 3-6 keywords ID MAMMALIAN-CELLS; CYTOSINE METHYLATION; DRUG-RESISTANCE; COLON-CANCER; NITRIC-OXIDE; P53 GENE; METHYLTRANSFERASE; HYPERMETHYLATION; INHIBITORS; MUTATIONS AB This paper examines the relationship between DNA mutagenic lesions, DNA methylation and the involvement of these changes in the process of carcinogenesis. Many types of DNA damage (oxidative lesions, alkylation of bases, abasic sites, photodimers, etc.) interfere with the ability of mammalian cell DNA to be methylated at CpG dinucleotides by DNA-methyltransferases (DNA-MTases). This can result in altered patterns in the distribution of 5-methylcytosine (5MeC) residues at CpG sites. Methylation of DNA is an epigenetic change that by definition is heritable, can result in changes in chromatin structure, and is often accompanied by modified patterns of gene expression. The presence of 5MeC in DNA, as well as oxidative stress induced by the free radical nitric oxide, can interefere with the repair of alkylation damage, thereby increasing the level of potentially mutagenic lesions. CpG sites in DNA represent mutational hotspots, with both the presence of 5MeC in DNA and the catalytic activity of DNA-MTases being intrinsically mutagenic. The process of carcinogenesis has frequently been associated with an increased expression of DNA-MTase activity, accompanied by either hypermethylation or hypomethylation of target cell (progenitor tumor cell) DNA. In addition, there is evidence that overexpression of DNA-MTase activity could result in increased cytosine methylation at non-CpG sites. A variety of chemicals can alter the extent of DNA methylation in mammalian cells. These include inhibitors of topoisomerase II, as well as inhibitors of DNA synthesis, microtubule formation, histone deacetylation, transmethylation, etc. Genetic and epigenetic changes in DNA have a profound influence on one another and could play a major role in the process of carcinogenesis, by modulating both the extent and the pattern of gene expression. RP Wachsman, JT (reprint author), NATL INST ENVIRONM HLTH SCI,ENVIRONM TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709, USA. NR 55 TC 77 Z9 84 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD APR 14 PY 1997 VL 375 IS 1 BP 1 EP 8 DI 10.1016/S0027-5107(97)00003-1 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA WU893 UT WOS:A1997WU89300001 PM 9129674 ER PT J AU deSerres, FJ Webber, BB AF deSerres, FJ Webber, BB TI Quantitative and qualitative comparisons of spontaneous and radiation-induced specific-locus mutation in the ad-3 region of heterokaryon 12 of Neurospora crassa SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE heterokaryon 12; gene/point mutation; multilocus deletion mutation; ad-3 region; ad-3A locus; ad-3B locus; recessive lethal mutation; ad-3(R)/ad-3(IR) ratio; ad-3B(R-C)/ad-3B(R-NC) ratio; allelic complementation; spontaneous; 250 kVp X-ray; UV; P-32; Sr-85; 101 MeV carbon ion; 39 MeV helium ion; 447 MeV proton; ad-3 forward-mutation assay; Neurospora crassa; genetic risk assessment ID GENETIC RISK ASSESSMENT; 2-COMPONENT HETEROKARYONS; IONIZING-RADIATION; SACCHAROMYCES-CEREVISIAE; HUMAN EXPOSURE; INDUCTION; SEQUENCE; SYSTEMS; ASSAY AB The data from forward-mutation experiments to obtain specific-locus mutations at two closely linked loci in the adenine-3 (ad-3) region of heterokaryon 12 (H-12) of Neurospora crassa have been used to determine the relative frequencies and mutational spectra of ad-3 mutants occurring spontaneously and those induced by 7 different radiation treatments. Previous studies have demonstrated that specific-locus mutants at these two loci result from 5 major genotypic classes, namely two classes of gene/point mutations (ad-3A(R) and ad-3B(R)), and 3 classes of multilocus deletion mutations ([ad-3A](IR), [ad-3B](IR) and [ad-3A ad-3B](IR)). Two different approaches were used to compare spontaneous mutation in the ad-3 region with that induced by 7 different radiation treatments (UV, P-32, 447 MeV protons, Sr-85, 250 kVp X-rays, 39 MeV helium ions, and 101 MeV carbon ions). These comparisons included (2)(chi)-tests on the numbers of ad-3 mutants resulting in the following two sets of ratios: (1) gene/point mutations and multilocus deletion mutations; and (2) complementing and non-complementing ad-3B(R) mutants. Combination of the data from these two methods of comparison has demonstrated that each of the 7 radiation treatments induced a spectrum of ad-3 mutants that is statistically different from the spontaneous spectrum. In addition, these same two methods of comparison have been used to compare the mutagenic effects of each of the 7 radiation treatments with each other. Combination of the data from these two methods of comparison demonstrated that the majority of radiation-induced specific-locus mutations: (90.5% (19/21 of the pairwise combinations)) are qualitatively different from each other. We conclude that the mechanisms by which various radiations modify DNA tend to exhibit fundamental differences from each other and from the processes involved in spontaneous mutation. C1 MED COLL GEORGIA,DEPT CELL & MOL BIOL,AUGUSTA,GA 30912. RP deSerres, FJ (reprint author), NATL INST ENVIRONM HLTH SCI,TOXICOL LAB,ENVIRONM TOXICOL PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 40 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD APR 14 PY 1997 VL 375 IS 1 BP 37 EP 52 DI 10.1016/S0027-5107(96)00253-9 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA WU893 UT WOS:A1997WU89300005 PM 9129678 ER PT J AU deSerres, FJ Malling, HV Brockman, HE Ong, TM AF deSerres, FJ Malling, HV Brockman, HE Ong, TM TI Quantitative and qualitative comparison of spontaneous and chemical-induced specific-locus mutation in the ad-3 region of heterokaryon 12 of Neurospora crassa SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE heterokaryon 12; gene/point mutation; multilocus deletion mutation; ad-3 region; ad-3A locus; ad-3B locus; recessive lethal mutation; ad-3R/[ad-3](IR) ratio; ad-3B(R-C)/ad-3B(R-NC) ratio; spontaneous mutation; chemical-induced mutation; allelic complementation; genetic risk assessment ID GENETIC RISK ASSESSMENT; RADIATION-INDUCED MUTATIONS; EXCISION-REPAIR-PROFICIENT; ENVIRONMENTAL CHEMICALS; IONIZING-RADIATION; MUTAGENIC ACTIVITY; 2-COMPONENT HETEROKARYONS; HUMAN EXPOSURE; INDUCTION; DAMAGE AB The data from forward-mutation experiments to obtain specific-locus mutations at two closely linked loci in the adenine-3 (ad-3) region of heterokaryon 12 (H-12) of Neurospora crassa have been tabulated to determine the relative frequencies and mutational spectra of ad-3 mutants occurring spontaneously and those induced by 22 different chemical treatments. Previous studies have demonstrated that specific-locus mutations at these two loci result from 5 major genotypic classes, namely two classes of gene/point mutations (ad-3A(R) and ad-3B(R)), and 3 classes of multilocus deletion mutations ([ad-3A](IR), [ad-3B](IR) and [ad-3A ad-3B](IR)). In addition, prior studies have demonstrated that some chemical mutagens induced ad-3 mutants exclusively, or almost exclusively, by gene/point mutation and other chemical mutagens by gene/point mutation and multilocus deletion mutation. In the latter cases, there was wide variation in the percentages of ad-3 mutants in these 5 major genotypic classes. Two comparative methods of analysis that also were used to compare spontaneous and chemical-induced ad-3 mutational spectra included chi(2)-tests on the numbers of ad-3 mutants resulting in the following two sets of ratios: (1) gene/point mutations and multilocus deletion mutations; and (2) complementing and non-complementing ad-3B(R) mutants. Combination of the p-values from chi(2)-tests for these two methods of comparison demonstrated that all 22 chemicals induce a spectrum of ad-3 mutants that is qualitatively different from that occurring spontaneously. In addition, these same two methods of comparison have been used to compare the mutagenic effects of each of the 22 chemical treatments with each other. Combination of the data from these two methods of comparison has demonstrated that 93.1% (215/231) of the pairwise combinations of these 22 chemicals were different from each other. The implication of these experimental data on the induction of specific-locus mutations in somatic cells of Neurospora for genetic risk assessment exercises is discussed. C1 ILLINOIS STATE UNIV,DEPT BIOL SCI,NORMAL,IL 61761. NIOSH,DIV RESP DIS STUDIES,MICROBIOL SECT,MORGANTOWN,WV 26505. RP deSerres, FJ (reprint author), NATL INST ENVIRONM HLTH SCI,,TOXICOL LAB,SYST TOXICOL BRANCH,ENVIRONM TOXICOL PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 38 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD APR 14 PY 1997 VL 375 IS 1 BP 53 EP 72 DI 10.1016/S0027-5107(96)00254-0 PG 20 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA WU893 UT WOS:A1997WU89300006 PM 9129679 ER PT J AU Glowa, JR Rice, KC Matecka, D Rothman, RB AF Glowa, JR Rice, KC Matecka, D Rothman, RB TI Phentermine/fenfluramine decreases cocaine self-administration in rhesus monkeys SO NEUROREPORT LA English DT Article DE cocaine; drug abuse; fenfluramine; food-maintained behavior; phentermine; rhesus monkeys; self-administration behavior ID DRUGS; LIABILITY AB Dopaminergic agonists can decrease cocaine self-administration at doses that do not decrease food-maintained responding, a pre-clinical effect indicative of a potential treatment for human cocaine abuse. To assess whether similar effects could be obtained with medications currently used to treat substance abuse, phentermine and fenfluramine were given alone and in combination to rhesus monkeys responding under schedules of food and cocaine delivery. Phentermine decreased cocaine-maintained responding with no effect on food-maintained responding. Fenfluramine also selectively decreased cocaine-maintained responding, but only at the highest dose. Combining a lower dose of fenfluramine with phentermine selectively decreased cocaine-maintained responding, but not more than with phentermine alone. These results suggest that phentermine, as well as its combination with fenfluramine, may be useful in the treatment of cocaine abuse. C1 NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD 21224. LOUISIANA STATE UNIV,MED CTR,DEPT PHARMACOL & THERAPEUT,SHREVEPORT,LA 71130. RP Glowa, JR (reprint author), UNIFORMED SERV UNIV HLTH SCI,DEPT PSYCHIAT,4301 JONES BRIDGE RD,BETHESDA,MD 20814, USA. FU NIDA NIH HHS [R01 DA09820-01]; ONDIEH CDC HHS [RA-ND-94-24] NR 25 TC 44 Z9 44 U1 1 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD APR 14 PY 1997 VL 8 IS 6 BP 1347 EP 1351 DI 10.1097/00001756-199704140-00006 PG 5 WC Neurosciences SC Neurosciences & Neurology GA XB174 UT WOS:A1997XB17400008 PM 9172133 ER PT J AU Gale, MJ Korth, MJ Tang, NM Tan, SL Hopkins, DA Dever, TE Polyak, SJ Gretch, DR Katze, MG AF Gale, MJ Korth, MJ Tang, NM Tan, SL Hopkins, DA Dever, TE Polyak, SJ Gretch, DR Katze, MG TI Evidence that hepatitis C virus resistance to interferon is mediated through repression of the PKR protein kinase by the nonstructural 5A protein SO VIROLOGY LA English DT Article ID DOUBLE-STRANDED-RNA; POLYMERASE CHAIN-REACTION; TRANSLATIONAL CONTROL; MALIGNANT TRANSFORMATION; CELLULAR INHIBITOR; MOLECULAR-CLONING; INFLUENZA-VIRUS; MESSENGER-RNAS; MR 68,000; CELLS AB Hepatitis C virus (HCV) is the major cause of non-A non-B hepatitis and a leading cause of liver dysfunction worldwide. While the current therapy for chronic HCV infection is parenteral administration of type 1 interferon (IFN), only a fraction of HCV-infected individuals completely respond to treatment. Previous studies have correlated the [FN sensitivity of strain HCV-1b with mutations within a discrete region of the viral nonstructural 5A protein (NS5A), termed the interferon sensitivity determining region (ISDR), suggesting that NS5A may contribute to the IFN-resistant phenotype of HCV. To determine the importance of HCV NS5A and the NS5A ISDR in mediating HCV IFN resistance, we tested whether the NS5A protein could regulate the IFN-induced protein kinase, PKR, a mediator of IFN-induced antiviral resistance and a target of viral and cellular inhibitors. Using multiple approaches, including biochemical, transfection, and yeast genetics analyses, we can now report that NS5A represses PKR through a direct interaction with the protein kinase catalytic domain and that both PKR repression and interaction requires the ISDR. Thus, inactivation of PKR may be one mechanism by which HCV avoids the antiviral effects of IFN. Finally, the inhibition of the PKR protein kinase by NS5A is the first described function for this HCV protein. (C) 1997 Academic Press. C1 UNIV WASHINGTON,DEPT MICROBIOL,SEATTLE,WA 98195. UNIV WASHINGTON,REG PRIMATE RES CTR,SEATTLE,WA 98195. NICHHD,EUKARYOT GENE REGULAT LAB,NIH,BETHESDA,MD 20892. UNIV WASHINGTON,DEPT LAB MED,SEATTLE,WA 98144. PACIFIC PRESBYTERIAN MED CTR,SEATTLE,WA 98144. RI Polyak, Stephen/B-5743-2011; OI Gale, Michael/0000-0002-6332-7436 FU NCRR NIH HHS [RR 00166]; NIAID NIH HHS [AI 22646]; NIGMS NIH HHS [T32 GM07270] NR 64 TC 623 Z9 642 U1 3 U2 13 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 APR 14 PY 1997 VL 230 IS 2 BP 217 EP 227 DI 10.1006/viro.1997.8493 PG 11 WC Virology SC Virology GA WV204 UT WOS:A1997WV20400008 PM 9143277 ER PT J AU Cleland, JL Duenas, ET Lim, A Daugherty, A Barron, L Wrin, T Vennari, J Murthy, KK Kaslow, D Powell, MF AF Cleland, JL Duenas, ET Lim, A Daugherty, A Barron, L Wrin, T Vennari, J Murthy, KK Kaslow, D Powell, MF TI Single administration vaccine formulation development SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 GENENTECH INC,DEPT PHARMACEUT R&D,S SAN FRANCISCO,CA 94080. GENENTECH INC,DEPT CELL BANKING & CHARACTERIZATION,S SAN FRANCISCO,CA 94080. SW FDN BIOMED RES,SAN ANTONIO,TX 78284. NIAID,MALARIA VACCINE SECT,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 17 EP BIOT PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18500612 ER PT J AU Polis, MA AF Polis, MA TI Current therapy and management of cytomegalovirus infection in persons with HIV infection. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIAID,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 20 EP CARB PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18500914 ER PT J AU Nasr, ME AF Nasr, ME TI Computerized HIV and OI's information database systems SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIAID,DIV AIDS,NIH,BETHESDA,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 23 EP CINF PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18502101 ER PT J AU Marquez, VE AF Marquez, VE TI The bicyclo[3.1.0]hexane template as a carbohydrate surrogate for the construction of anti-HCMV nucleosides. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,MED CHEM LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 26 EP CARB PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18500920 ER PT J AU Coxon, B Sari, N Mulard, LA Kovac, P Glaudemans, CPJ Pozsgay, V AF Coxon, B Sari, N Mulard, LA Kovac, P Glaudemans, CPJ Pozsgay, V TI Investigation by NMR spectroscopy and molecular mechanics of the conformations of some modified disaccharide antigens for Shigella dysenteriae type 1. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIST,DIV BIOTECHNOL,GAITHERSBURG,MD 20899. NIDDK,MED CHEM LAB,NIH,BETHESDA,MD 20892. NICHHD,DEV & MOL IMMUN LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 27 EP BIOT PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18500622 ER PT J AU Hazard, GF Hudson, VW AF Hazard, GF Hudson, VW TI Online pesticide resources at the Toxicology and Environmental Health Information Program. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NATL LIB MED,BETHESDA,MD 20894. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 29 EP CINF PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18502107 ER PT J AU Wang, J Zhang, J Fournier, JM Kovac, P Szu, SC Glaudemans, CPJ AF Wang, J Zhang, J Fournier, JM Kovac, P Szu, SC Glaudemans, CPJ TI Studies towards a synthetic vaccine for cholera. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. NICHHD,BETHESDA,MD 20892. INST PASTEUR,F-75724 PARIS 15,FRANCE. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 32 EP BIOT PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18500627 ER PT J AU Hong, HX Wang, SM Nicklause, MC Milne, GWA AF Hong, HX Wang, SM Nicklause, MC Milne, GWA TI HIV-1 integrase pharmacophore identification. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,MED CHEM LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 38 EP COMP PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18502670 ER PT J AU Wang, S Blumberg, PM Milne, GWA Kozikowski, AP AF Wang, S Blumberg, PM Milne, GWA Kozikowski, AP TI Does a common pharmacophore really exist? A lesson learned from the studies of protein kinase C system. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 40 EP COMP PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18502672 ER PT J AU Zhang, HS Basille, AS Skolnick, P Fryer, RI AF Zhang, HS Basille, AS Skolnick, P Fryer, RI TI A novel family of Peripheral Benzodiazepine Receptor (PBR) ligands. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDKD,NEUROSCI LAB,NIH,BETHESDA,MD 20892. RUTGERS STATE UNIV,DEPT CHEM,NEWARK,NJ 07102. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 41 EP MEDI PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP187 UT WOS:A1997WP18701066 ER PT J AU Kim, YC Ji, XD Olah, ME Stiles, GL Jacobson, KA AF Kim, YC Ji, XD Olah, ME Stiles, GL Jacobson, KA TI Highly potent and selective human adenosine A3 receptor antagonists: Triazoloquinazoline derivatives. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 DUKE UNIV,MED CTR,DEPT MED & PHARMACOL,DURHAM,NC 27710. NIH,BIOORGAN CHEM LAB,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 42 EP MEDI PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP187 UT WOS:A1997WP18701067 ER PT J AU Price, KN Johnson, SC Baker, DC Chisena, T Cysyk, RL AF Price, KN Johnson, SC Baker, DC Chisena, T Cysyk, RL TI Anti-metastatic oligosaccharides and analogues from hyaluronic acid. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 UNIV TENNESSEE,DEPT CHEM,KNOXVILLE,TN 37996. NCI,MED CHEM LAB,DIV BASIC SCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 46 EP CARB PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18500940 ER PT J AU Burke, JR Ye, B AF Burke, JR Ye, B TI Synthesis of a new tyrosine analogue having X(1) and X(2) angles constrained to values observed for an SH2 domain-bound phosphotyrosyl residue. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,MED CHEM LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 56 EP ORGN PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP187 UT WOS:A1997WP18701501 ER PT J AU Jernigan, RL Bahar, I Flatow, D Raghunathan, G Kloczkowski, A AF Jernigan, RL Bahar, I Flatow, D Raghunathan, G Kloczkowski, A TI Proteins: Diversities and similarities. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,MOL STRUCT SECT,MATH BIOL LAB,NIH,BETHESDA,MD 20892. RI Jernigan, Robert/A-5421-2012; Kloczkowski, Andrzej/B-9868-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 77 EP COMP PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18502709 ER PT J AU Southan, GJ George, C Keefer, LK AF Southan, GJ George, C Keefer, LK TI Identification of nitric oxide donors from the nitrosation of hydroxyguanidines. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 USN,RES LAB,WASHINGTON,DC 20375. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,IRSP,SAIC,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 86 EP MEDI PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP187 UT WOS:A1997WP18701111 ER PT J AU Hodosi, G Kovac, P AF Hodosi, G Kovac, P TI A fundamentally new, simple, stereospecific synthesis of oligosaccharides containing the beta-mannopyranosyl and beta-rhamnopyranosyl linkage SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,NIH,LMC SC,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 88 EP CARB PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18500982 ER PT J AU Li, G Waltham, M Anderson, NL Weinstein, JN AF Li, G Waltham, M Anderson, NL Weinstein, JN TI Improvements on sample handling for rapid mass spectrometric identification of proteins resolved by 2D gel electrophoresis. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. LARGE SCALE BIOL CORP,ROCKVILLE,MD 20850. RI Waltham, Mark/A-1728-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 92 EP ANYL PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18500447 ER PT J AU Srinivasan, A Saavedra, JE Booth, M Keefer, LK AF Srinivasan, A Saavedra, JE Booth, M Keefer, LK TI O-2-aryl diazen-1-ium-1,2-diolates as nitric oxide releasing agents. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. IRSP,SAIC FREDERICK,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 101 EP ORGN PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP187 UT WOS:A1997WP18701546 ER PT J AU Crowley, MF AF Crowley, MF TI Fine and coarse grain parallel AMBER and Particle-Mesh Ewald on MPP's. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 PITTSBURGH SUPERCOMP CTR,PITTSBURGH,PA. NIEHS,BETHESDA,MD. UC,SAN FRANCISCO,CA. RI crowley, michael/A-4852-2013 OI crowley, michael/0000-0001-5163-9398 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 113 EP COMP PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18502745 ER PT J AU Huang, XL Appella, D Christinson, L Klein, D Gellman, SH Barchi, JJ AF Huang, XL Appella, D Christinson, L Klein, D Gellman, SH Barchi, JJ TI Solution structures of constrained beta-amino acid oligomers. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,MED CHEM LAB,BETHESDA,MD 20892. NCI,DIV BASIC SCI,BETHESDA,MD 20892. UNIV WISCONSIN,DEPT CHEM,MADISON,WI 53706. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 137 EP MEDI PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP187 UT WOS:A1997WP18701162 ER PT J AU Noronha, SB Trinh, LB Kaslow, DC Shiloach, J AF Noronha, SB Trinh, LB Kaslow, DC Shiloach, J TI Optimization of fed-batch S-cerevisiae fermentation of a malaria transmission antigen under the control of the ADH2 promoter. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 150 EP BIOT PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18500743 ER PT J AU Holmquist, CR KeverlineFrantz, KI Abraham, P Boja, JW Kuhar, MJ Carroll, FI AF Holmquist, CR KeverlineFrantz, KI Abraham, P Boja, JW Kuhar, MJ Carroll, FI TI 3 alpha-(substituted phenyl)tropane-2 beta-carboxylic acid esters: Ligands with unexpectedly high affinity and selectivity at the dopamine transporter. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 191 EP MEDI PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP187 UT WOS:A1997WP18701215 ER PT J AU Lomenzo, SA Izenwasser, S Katz, JL Trudell, ML AF Lomenzo, SA Izenwasser, S Katz, JL Trudell, ML TI Synthesis and biological activity of novel 6-alkyl-3-benzyl-2-(methoxycarbonylmethyl)tropane derivatives. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 UNIV NEW ORLEANS,DEPT CHEM,NEW ORLEANS,LA 70148. NIDA,DIV INTRAMURAL RES,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 192 EP MEDI PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP187 UT WOS:A1997WP18701216 ER PT J AU Eaton, WA AF Eaton, WA TI Early events in protein folding. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH,PHYS CHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 208 EP PHYS PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP187 UT WOS:A1997WP18702466 ER PT J AU Subramanian, PK Tseng, CC Vishnuvajjala, R Stevens, A AF Subramanian, PK Tseng, CC Vishnuvajjala, R Stevens, A TI Synthesis and cytotoxicity of androstanyl ureas as dolastatin 10 model candidates. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 ASH STEVENS INC,DETROIT,MI 48202. NIH,PHARMACEUT RESOURCES BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 210 EP MEDI PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP187 UT WOS:A1997WP18701234 ER PT J AU Christodoulou, D Chu, J Derouff, W Wink, DA AF Christodoulou, D Chu, J Derouff, W Wink, DA TI Linked acridine derivatives with S-nitroso-beta-aminothiols and their radiation sensitization properties. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,CHEM SECT,FREDERICK,MD 21702. NCI,RADIAT BIOL BRANCH,FREDERICK,MD 21892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 211 EP MEDI PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP187 UT WOS:A1997WP18701235 ER PT J AU Saifer, MGP Williams, LD Sherman, MR French, JA Kwak, LW Oppenheim, JJ AF Saifer, MGP Williams, LD Sherman, MR French, JA Kwak, LW Oppenheim, JJ TI Improved conjugation of cytokines using high molecular weight poly(ethylene glycol): PEG-GM-CSF as a prototype. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 MT VIEW PHARMACEUT INC,SAN CARLOS,CA 94070. NCI,FREDERICK,MD 21702. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 213 EP POLY PN 2 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA WP187 UT WOS:A1997WP18702950 ER PT J AU Shi, LM Myers, TG Fan, Y Weinstein, JN AF Shi, LM Myers, TG Fan, Y Weinstein, JN TI Mining the NCI anticancer drug screen database using genetic function approximation (GFA) and cluster analysis. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,NIH,DBS,LMP,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 214 EP COMP PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18502846 ER PT J AU Fan, Y Shi, LM Myers, TG Weinstein, JN AF Fan, Y Shi, LM Myers, TG Weinstein, JN TI Quantitative structure-antitumor activity relationships of camptothecin analogs. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,LMP,DBS,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 253 EP COMP PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18502885 ER PT J AU Byrd, RA AF Byrd, RA TI Multidimensional NMR: Past, present, and future. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MACROMOL NMR SECT,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 265 EP POLY PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP187 UT WOS:A1997WP18703002 ER PT J AU Abashkin, YG Burt, SK AF Abashkin, YG Burt, SK TI Density functional modeling of enzymatic activities. Peptide bond cleavage by carboxypeptidase A and metal-substituted enzymes. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FREDERICK BIOMED SUPERCOMP CTR,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 269 EP COMP PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18502901 ER PT J AU Tutonda, MG Buckheit, RW Broom, AD AF Tutonda, MG Buckheit, RW Broom, AD TI Antiviral oligo and polyribonucleotides containing selected triazolo[2,3-a]purines SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 UNIV UTAH,SALT LAKE CITY,UT 84112. FREDERICK CANC RES & DEV CTR,SO RES INST,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 271 EP MEDI PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP187 UT WOS:A1997WP18701295 ER PT J AU Smith, MBK Boyer, PL Hughes, SH Michejda, CJ Smith, RH AF Smith, MBK Boyer, PL Hughes, SH Michejda, CJ Smith, RH TI Nonnucleoside inhibitor potency and polymerase efficiency against drug-resistant strains of HIV-1 reverse transcriptase: Correlation of computer modeling and experimental data. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 281 EP MEDI PN 2 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA WP187 UT WOS:A1997WP18701305 ER PT J AU Zhao, H Neamati, N Sunder, S Hong, HX Milne, GW Pommier, Y Burke, TR AF Zhao, H Neamati, N Sunder, S Hong, HX Milne, GW Pommier, Y Burke, TR TI Hydrazide-containing inhibitors of HIV-1 integrase SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,DIV BASIC SCI,MED CHEM LAB,NIH,BETHESDA,MD 20892. NCI,DIV BASIC SCI,MOL PHARMACOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 4 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 282 EP MEDI PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP187 UT WOS:A1997WP18701306 ER PT J AU Cushman, M He, HM Katzenellenbogen, JA Varma, RK Hamel, E Lin, CM VerdierPinard, P Ram, S Sachdeva, Y AF Cushman, M He, HM Katzenellenbogen, JA Varma, RK Hamel, E Lin, CM VerdierPinard, P Ram, S Sachdeva, Y TI Synthesis, antitubulin activity, and anticancer activity of more potent analogs in the 5-alkoxyestradiol series. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 PURDUE UNIV,SCH PHARM & PHARMACAL SCI,DEPT MED CHEM & MOL PHARMACOL,W LAFAYETTE,IN 47907. UNIV ILLINOIS,DEPT CHEM,URBANA,IL 61801. NCI,DRUG SYNTHESIS & CHEM BRANCH,BETHESDA,MD 20852. NCI,LAB DRUG DISCOVERY RES & DEV,FREDERICK,MD 21702. PHARMECO LABS INC,LEXINGTON,MA 02173. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 299 EP MEDI PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP187 UT WOS:A1997WP18701323 ER PT J AU Barchi, JJ Huang, XL Lung, FDT Roller, PP Garrity, RR Muschik, J AF Barchi, JJ Huang, XL Lung, FDT Roller, PP Garrity, RR Muschik, J TI Synthesis, structure and antibody binding of glycopeptides from immunogenic domains of HIV-I GP120. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,MED CHEM LAB,BETHESDA,MD 20892. NCI,DIV BASIC SCI,FREDERICK CANC RES & DEV CTR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 310 EP MEDI PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP187 UT WOS:A1997WP18701334 ER PT J AU Burke, TR Yao, ZJ Ye, B Wang, SM Zhang, ZY AF Burke, TR Yao, ZJ Ye, B Wang, SM Zhang, ZY TI Structure-based design of protein-tyrosine phosphatase 1B inhibitors. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,MED CHEM LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. YESHIVA UNIV ALBERT EINSTEIN COLL MED,BRONX,NY 10461. RI Yao, Zhu-Jun/E-7635-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 313 EP MEDI PN 2 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA WP187 UT WOS:A1997WP18701337 ER PT J AU Adamczeski, M Tomioka, K White, W AF Adamczeski, M Tomioka, K White, W TI The use of chiral derivatization reagents to resolve enantiomeric pairs of endo- and exo-norborneols through H-1 NMR spectroscopy and molecular modeling calculations. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 AMERICAN UNIV,DEPT CHEM,WASHINGTON,DC 20016. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 340 EP CHED PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA WP185 UT WOS:A1997WP18501486 ER PT J AU McDiarmid, R Xing, X AF McDiarmid, R Xing, X TI Experimental assignments and evaluations of recent acetone and formaldehyde excited state calculations SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 440 EP PHYS PN 2 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA WP187 UT WOS:A1997WP18702695 ER PT J AU Behar, MG AF Behar, MG TI Reflections on a career in research teaching and science administration. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,DIV RES GRANTS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 13 PY 1997 VL 213 BP 468 EP INOR PN 2 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA WP187 UT WOS:A1997WP18700632 ER PT J AU Moloney, DM Wall, SA Ashworth, GJ Oldridge, M Glass, IA Francomano, CA Muenke, M Wilkie, AOM AF Moloney, DM Wall, SA Ashworth, GJ Oldridge, M Glass, IA Francomano, CA Muenke, M Wilkie, AOM TI Prevalence of Pro250Arg mutation of fibroblast growth factor receptor 3 in coronal craniosynostosis SO LANCET LA English DT Article ID AUTOSOMAL-DOMINANT CRANIOSYNOSTOSIS; CROUZON-SYNDROME; PFEIFFER-SYNDROME; GENE CAUSE; FGFR2; FAMILY AB Background The C749G (Pro250Arg) mutation in the gene for fibroblast growth factor receptor 3 (FGFR3) has been found in patients with various types of craniosynostosis. We aimed to find out the proportion of cases of apparently nonsyndromic coronal craniosynostosis attributable to this mutation. Methods We studied 26 patients with coronal craniosynostosis but no syndromic diagnosis, who were referred to a supra-regional specialist centre. Genomic DNA was analysed by PCR and restriction-enzyme digestion to identify the C749G mutation in FGFR3, Family members of patients found to have the mutation were also tested. Findings Eight (31%) of the 26 probands were heterozygous for the C749G mutation. In two cases, the mutation showed autosomal dominant transmission with evidence of variable expressivity; the remaining six cases were sporadic. We demonstrated in six families that the mutation had arisen de novo from clinically unaffected parents. Interpretation The C749G mutation in FGFR3 is a frequent cause of apparently non-syndromic coronal craniosynostosis. Our finding will aid genetic counselling and prenatal diagnosis. The mutation rate at this nucleotide is one of the highest described in the human genome. C1 JOHN RADCLIFFE HOSP,INST MOL MED,OXFORD OX3 9DS,ENGLAND. RADCLIFFE INFIRM,OXFORD CRANIOFACIAL UNIT,OXFORD OX2 6HE,ENGLAND. MT SINAI SCH MED,DEPT HUMAN GENET,NEW YORK,NY. NIH,MED GENET BRANCH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. CHILDRENS HOSP PHILADELPHIA,DIV HUMAN GENET & MOL BIOL,PHILADELPHIA,PA 19104. FU Wellcome Trust NR 27 TC 97 Z9 98 U1 1 U2 3 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD APR 12 PY 1997 VL 349 IS 9058 BP 1059 EP 1062 DI 10.1016/S0140-6736(96)09082-4 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA WU002 UT WOS:A1997WU00200010 PM 9107244 ER PT J AU Vaupel, DB Kimes, AS London, ED AF Vaupel, DB Kimes, AS London, ED TI Further in vivo studies on attenuating morphine withdrawal: Isoform-selective nitric oxide synthase inhibitors differ in efficacy SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE morphine withdrawal; blood pressure; nitric oxide (NO) synthase inhibitor; 3-bromo-7-nitro indazole; aminoguanidine; S-methyl-L-thiocitrulline; 7-nitro indazole; nitric oxide (NO) ID NALOXONE-PRECIPITATED WITHDRAWAL; METHYL-L-THIOCITRULLINE; OPIOID WITHDRAWAL; 7-NITRO INDAZOLE; RECEPTOR ANTAGONISTS; OPIATE WITHDRAWAL; DEPENDENT MICE; POTENT; AMINOGUANIDINE; CLONIDINE AB The N-methyl-D-aspartate (NMDA) receptor-nitric oxide (NO) pathway has been linked to opiate withdrawal. Pretreatments with four inhibitors of NO synthase, 7-nitro indazole, 3-bromo-7-nitro indazole, S-methyl-L-thiocitrulline and aminoguanidine, which exhibit different isoform selectivity in vitro, were evaluated for their ability to attenuate signs of naloxone-precipitated morphine withdrawal. In separate experiments, effects of NO synthase inhibitors on blood pressure were measured in naive and morphine-dependent rats. 7-Nitro indazole, 3-bromo-7-nitro indazole and S-methyl-L-thiocitrulline, which are specific inhibitors of the constitutive isoforms, produced dose-dependent reductions of several signs of withdrawal. Blood pressure was unaffected by the indazoles, whereas S-methyl-L-thiocitrulline produced a strong vasoconstrictor response. Aminoguanidine, which selectively inhibits inducible NO synthase, reduced fewer signs of opioid withdrawal, had a lower relative potency and exhibited no vasopressor activity. These data suggest that constitutive isoforms, but not the inducible isoform of NO synthase, have a primary role in NO-mediated processes that modulate the opioid withdrawal syndrome in the rat. (C) 1997 Elsevier Science B.V. RP Vaupel, DB (reprint author), NIDA,INTRAMURAL RES PROGRAM,NEUROSCI BRANCH,BRAIN IMAGING SECT,POB 5180,BALTIMORE,MD 21224, USA. NR 36 TC 49 Z9 53 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD APR 11 PY 1997 VL 324 IS 1 BP 11 EP 20 DI 10.1016/S0014-2999(97)00061-7 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WV167 UT WOS:A1997WV16700002 PM 9137908 ER PT J AU Zambon, AC DeCosta, BR Kanthasamy, AG Nguyen, BQH Matsumoto, RR AF Zambon, AC DeCosta, BR Kanthasamy, AG Nguyen, BQH Matsumoto, RR TI Subchronic administration of N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine (BD1047) alters sigma(1) receptor binding SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE sigma receptor; cytotoxicity; regulation; internalization; (+)-pentazocine; desensitization ID GUINEA-PIG BRAIN; MONOAMINE-OXIDASE INHIBITORS; C57BL/6 MOUSE-BRAIN; ANTIPSYCHOTIC-DRUGS; RAT-BRAIN; MEDIATED ENDOCYTOSIS; HIGH-AFFINITY; LIGANDS; INVIVO; SITES AB BD1047 (N-[2-(3,4-dichlorophenyl)ethyl]-N-methy-2-(dimethylamino)ethylamine) is known to bind with high affinity and selectivity to a sites in vitro. In prior in vivo studies, it has been shown to attenuate the dystonic postures and orofacial dyskinesias that are produced by sigma receptor ligands, including the neuroleptic haloperidol. Since abnormal movements, such as dystonic postures and orofacial dyskinesias, are side effects that are associated with many sigma-active neuroleptics, compounds such as BD1047 may have therapeutic potential for preventing and treating these unwanted movements. A possible limitation to the therapeutic potential of BD1047, however, is that at least in cell culture and albeit weak, it can be cytotoxic. Therefore, the present study analyzed the possible neurotoxic effects of in vivo subchronic intracerebroventricular infusion of BD1047 (10 nmol/h) or artificial cerebrospinal fluid (CSF) into rat brains using osmotic minipumps for 7 or 14 days. Following a 24 h wash-out period, the animals were killed, the brains removed, and P-2 membranes prepared. Membranes from rats treated for 7 or 14 days with BD1047 showed a marked decrease in [H-3](+)-pentazocine binding as compared to membranes from CSF-treated animals, suggesting a loss of sigma(1) receptor binding. Histological examination of brain sections processed for Nissl stains and glial fibrillary acidic protein (GFAP) immunohistochemistry excluded the possibility of a cytotoxically induced down-regulation, suggesting possible receptor internalization or desensitization mediated via sigma(1) sites. Under the conditions used in our study, BD1047 does not appear to be neurotoxic, and the data, when taken together with other studies, suggest that BD1047 acts as a partial agonist at sigma sites. (C) 1997 Elsevier Science B.V. C1 UNIV OKLAHOMA,HLTH SCI CTR,COLL PHARM,DEPT PHARMACOL & TOXICOL,OKLAHOMA CITY,OK 73190. UNIV CALIF IRVINE,DEPT NEUROL,PARKINSON & MOVEMENT DISORDERS LAB,IRVINE,CA 92697. NIDDKD,MED CHEM LAB,NIH,BETHESDA,MD 20892. FU NIMH NIH HHS [MH50564] NR 38 TC 15 Z9 15 U1 0 U2 2 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 APR 11 PY 1997 VL 324 IS 1 BP 39 EP 47 DI 10.1016/S0014-2999(97)00053-8 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WV167 UT WOS:A1997WV16700005 PM 9137911 ER PT J AU Zuber, M Hoover, TA Dertzbaugh, MT Court, DL AF Zuber, M Hoover, TA Dertzbaugh, MT Court, DL TI A Francisella tularensis DNA clone complements Escherichia coli defective for the production of Era, an essential Ras-like GTP-binding protein SO GENE LA English DT Article DE aspC; cloning; mdh; sequencing; Tularemia ID STREPTOCOCCUS-MUTANS; RNC OPERON; EXPRESSION; GENE; LVS AB We cloned the era gene of Francisella tularensis from a plasmid library by heterologous genetic complementation of an Escherichia coli mutant conditionally defective for the production of Era, an essential protein for cell growth. Nucleotide sequence analysis indicated that, in F. tularensis, era constitutes a single gene operon. ORFs aspC and mdh encoding aspartate aminotransferase and malate dehydrogenase, respectively, Bank era in F. tularensis. Although classified as Gram(-), the flanking regions and the relative location of era in F. tularensis are distinctly different from those of typical Gram(-) and Gram(+) bacteria. Computer analysis of bacterial Era protein sequences identified conserved domains in addition to the common G domains of most GTP-binding proteins. (C) 1997 Elsevier Science B.V. C1 USA,MED RES INST INFECT DIS,BACTERIOL DIV,FT DETRICK,FREDERICK,MD 21702. USA,MED RES INST INFECT DIS,DIV TOXICOL,FT DETRICK,FREDERICK,MD 21702. RP Zuber, M (reprint author), NCI,MOL CONTROL & GENET SECT,GENE REGULAT & CHROMOSOME BIOL LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702, USA. NR 17 TC 23 Z9 29 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD APR 11 PY 1997 VL 189 IS 1 BP 31 EP 34 DI 10.1016/S0378-1119(96)00813-X PG 4 WC Genetics & Heredity SC Genetics & Heredity GA WX270 UT WOS:A1997WX27000006 PM 9161408 ER PT J AU Roberts, BJ AF Roberts, BJ TI Evidence of proteasome-mediated cytochrome P-450 degradation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LIVER MICROSOMAL CYTOCHROME-P-450; RAT-LIVER; PROTEIN STABILIZATION; OXYGEN ACTIVATION; TURNOVER; INDUCTION; CELLS; FORMS; ACIDOPHILUM; EXPRESSION AB The cytochrome P-450 family of enzymes performs an incredibly diverse range of detoxification and oxidation reactions within the cell and constitutes between 5 and 10% of protein in hepatic endoplasmic reticulum. In this report it is demonstrated that constitutively expressed membranous P-450s are targeted for destruction by the proteasome, in a process which is ubiquitin-independent and is demonstrated in vitro to require prior labilization of the enzyme. This process was specific for P-450s CYP1A2, CYP2E1, CYP3A, and CYP4A and was not demonstrated to be involved in the turnover of CYP1A1, CYP2B1/2, or NADPH reductase. In reconstitution experiments using purified proteasomes and microsomal fractions, labilized P-450 conformations are protected from 20 S proteasome degradation by substrate addition, with proteolysis occurring while P-450s are still attached to the endoplasmic reticulum. RP Roberts, BJ (reprint author), NIAAA,CLIN STUDIES LAB,10 CTR DR,MSC-1256,BETHESDA,MD 20892, USA. NR 40 TC 91 Z9 93 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 APR 11 PY 1997 VL 272 IS 15 BP 9771 EP 9778 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WU039 UT WOS:A1997WU03900029 PM 9092510 ER PT J AU Sharf, R Meraro, D Azriel, A Thornton, AM Ozato, K Petricoin, EF Larner, AC Schaper, F Hauser, H Levi, BZ AF Sharf, R Meraro, D Azriel, A Thornton, AM Ozato, K Petricoin, EF Larner, AC Schaper, F Hauser, H Levi, BZ TI Phosphorylation events modulate the ability of interferon consensus sequence binding protein to interact with interferon regulatory factors and to bind DNA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STIMULATED RESPONSE ELEMENT; TRANSCRIPTION FACTOR IRF-1; CELL-GROWTH INHIBITION; FACTOR FAMILY; GAMMA-INTERFERON; GENE-EXPRESSION; INDUCIBLE GENES; FACTOR-I; TYROSINE; IFN AB Two families of transcription factors mediate interferon (IFN) signaling, The first family, signal transducers and activators of transcription (STATs), is activated within minutes of IFN treatment. Specific phosphorylation events lead to their translocation to the nucleus, formation of transcriptional complexes, and the induction of the second family of transcription factors termed interferon regulatory factors (IRFs). Interferon consensus sequence binding protein (ICSBP) is a member of IRF family that is expressed only in cells of the immune system and acts as a transcriptional repressor. ICSBP binds DNA through the association with other transcription factors such as IRF-1 or IRF-2. In this communication, the domain that is involved in protein-protein interactions was mapped to the carboxyl terminus of ICSBP. This domain is also important for mediating ICSBP repressing activity. In vitro studies demonstrated that direct binding of ICSBP to DNA is prevented by tyrosine (Tyr) phosphorylation. Yet, Tyr-phosphorylated ICSBP can bind target DNA only through the association with IRF-2 and IRF-1. This type of phosphorylation is essential for the formation of heterocomplexes. Tyr-phosphorylated ICSBP and IRF-2 are detected in expressing cells constitutively, and Tyr-phosphorylated IRF-1 is induced by IFN-gamma. These results strongly suggest that like the STATs, the IRFs are also modulated by Tyr phosphorylation that affects their biological activities. C1 TECHNION ISRAEL INST TECHNOL,DEPT FOOD ENGN & BIOTECHNOL,IL-32000 HAIFA,ISRAEL. NICHHD,LAB MOL GROWTH REGULAT,NIH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT,DIV CYTOKINE BIOL,BETHESDA,MD 20892. GESELL BIOTECHNOL FORSCH MBH,D-38124 BRAUNSCHWEIG,GERMANY. RI Schaper, Fred/F-1403-2013 NR 43 TC 140 Z9 143 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 APR 11 PY 1997 VL 272 IS 15 BP 9785 EP 9792 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WU039 UT WOS:A1997WU03900031 PM 9092512 ER PT J AU Kelm, M Dahmann, R Wink, D Feelisch, M AF Kelm, M Dahmann, R Wink, D Feelisch, M TI The nitric oxide superoxide assay - Insights into the biological chemistry of the NO/O-2(-center dot) interaction SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CORONARY VASCULAR TONE; RESONANCE SPECTROSCOPY; HYDROGEN-PEROXIDE; ENDOTHELIAL-CELLS; ANION PRODUCTION; PEROXYNITRITE; KINETICS; NO; HYPERTENSION; MECHANISMS AB Nitric oxide (NO) is a widespread signaling molecule involved in the regulation of an impressive spectrum of diverse cellular functions. Superoxide anions (O-2(radical anion)) not only contribute to the localization of NO action by rapid inactivation, but also give rise to the formation of the potentially toxic species peroxynitrite (ONOO-) and other reactive nitrogen oxide species. The chemistry and biological effect of ONOO- depend on the relative rates of formation of NO and O-2(radical anion). However, the simultaneous quantification of NO and O-2(radical anion) has not been achieved yet due to their high rate of interaction, which is almost diffusion-controlled. A sensitive spectrophoto metric assay was developed for the simultaneous quantification of NO and O-2(radical anion) in aqueous solution that is based on the NO-induced oxidation of oxyhemoglobin (oxyHb) to methemoglobin and the O-2(radical anion)-mediated reduction of ferricytochrome c. Using a photodiode array photometer, spectral changes of either reaction were analyzed, and appropriate wavelengths were identified for the simultaneous monitoring of absorbance changes of the individual reactions, oxyHb oxidation was followed at 541.2 nm (isosbestic wavelength for the conversion of ferri- to ferrocytochrome c), and ferricytochrome c reduction was followed at 465 nm (wavelength at which absorbance changes during oxyHb to methemoglobin conversion were negligible), using 525 nm as the isosbestic point for both reactions, At final concentrations of 20 mu M ferricytochrome c and 5 mu M oxyHb, the molar extinction coefficients were determined to be epsilon(465-525) = 7.3 mM(-1) cm(-1) and epsilon(541.2-525) = 6.6 mM(-1) cm(-1), respectively. The rates of formation of either NO or O-2(radical anion) determined with the combined assay were virtually identical to those measured with the classical oxyhemoglobin and cytochrome c assays, respectively. The assay was successfully adapted to either kinetic or end point determination in a cuvette or continuous on-line measurement of both radicals in a flow-through system. Maximal assay sensitivity was -25 nM for NO and O-2(radical anion). Cross-reactivity with ONOO- was controlled for by the presence (if L-methionine. Generation of NO from the NO donor spermine diazeniumdiolate could be reliably quantified in the presence and absence of low, equimolar, and high flux rates of O-2(radical anion). Likewise, O-2(radical anion) enzymatically generated from hypoxanthine/xanthine oxidase could be specifically quantified with no difference in absolute rates in the presence or absence of concomitant NO generation at different flux rates. Nonenzymatic decomposition of 3-morpholinosydnonimine hydrochloride (100 mu M) in phosphate buffer, pH 7.4 (37 degrees C), was found to be associated with almost stoichiometric production of NO and O-2(radical anion) (1.24 mu M NO/min and 1.12 mu M O-2(radical anion)/min). Assay selectivity and applicability to biological systems were demonstrated in cultured endothelial cells and isolated aortic tissue using calcium ionophore and NADH for stimulation of NO and O-2(radical anion) formation, respectively. Based on these data, a computer model was elaborated that successfully predicts the reaction of NO and O-2(radical anion) with hemoprotein and may thus help to further elucidate these reactions. In conclusion, the nitric oxide/superoxide assay allows the specific, sensitive, and simultaneous detection of NO and O-2(radical anion). The simulation model developed also allows the reliable prediction of the reaction between NO and O-2(radical anion) as well as their kinetic interaction with other biomolecules. These new analytical tools will help to gain further insight into the physiological and pathophysiological significance of the formation of these radicals in cell homeostasis. C1 UNIV DUSSELDORF,DEPT MED,DIV CARDIOL PULM DIS & ANGIOL,D-40225 DUSSELDORF,GERMANY. NCI,TUMOR BIOL SECT,RADIAT BIOL BRANCH,NIH,BETHESDA,MD 20892. RI Feelisch, Martin/C-3042-2008 OI Feelisch, Martin/0000-0003-2320-1158 NR 57 TC 138 Z9 149 U1 1 U2 8 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 APR 11 PY 1997 VL 272 IS 15 BP 9922 EP 9932 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WU039 UT WOS:A1997WU03900050 PM 9092531 ER PT J AU Liu, YC Liu, YH Elly, C Yoshida, H Lipkowitz, S Altman, A AF Liu, YC Liu, YH Elly, C Yoshida, H Lipkowitz, S Altman, A TI Serine phosphorylation of Cbl induced by phorbol ester enhances its association with 14-3-3 proteins in T cells via a novel serine-rich 14-3-3-binding motif SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID C-CBL; PHOSPHATIDYLINOSITOL 3-KINASE; V-CBL; TYROSINE PHOSPHORYLATION; PROTOONCOGENE PRODUCT; SIGNAL-TRANSDUCTION; ANTIGEN RECEPTOR; JURKAT CELLS; SH3 DOMAIN; 14-3-3-PROTEINS AB Stimulation of the T cell antigen receptor (TCR)-CD3 complex induces rapid tyrosine phosphorylation of Cbl, a protooncogene product which has been implicated in intracellular signaling pathways via its interaction with several signaling molecules. We found recently that Cbl associates directly with a member of the 14-3-3 protein family (14-3-3 tau) in T cells and that the association is increased as a consequence of anti CD3-mediated T cell activation. We report here that phorbol la myristate 13-acetate stimulation of T cells also enhanced the interaction between Cbl and two 14-3-3 isoforms (tau and zeta). Tyrosine phosphorylation of Cbl was not sufficient or required for this increased interaction. Thus, cotransfection of COS cells with Cbl plus Lck and/or Syk family protein-tyrosine kinases caused a marked increase in the phosphotyrosine content of Cbl without a concomitant enhancement of its association with 14-3-3. Phorbol 12-myristate 13-acetate stimulation induced serine phosphorylation of Cbl, and dephosphorylation of immunoprecipitated Cbl by a Ser/Thr phosphatase disrupted its interaction with 14-3-3. By using successive carboxyl-terminal deletion mutants of Cbl, the 14-3-3-binding domain was mapped to a serine-rich 30-amino acid region (residues 615-644) of Cbl. Mutation of serine residues in this region further defined a binding motif distinct from the consensus sequence RSXSXP, which was recently identified as a 14-3-3-binding motif. These results suggest that TCR stimulation induces both tyrosine and serine phosphorylation of Cbl. These phosphorylation events allow Cbl to recruit distinct signaling elements that participate in TCR-mediated signal transduction pathways. C1 LA JOLLA INST ALLERGY & IMMUNOL, DIV CELL BIOL, SAN DIEGO, CA 92121 USA. INST CYTOSIGNAL RES INC, TOKYO 140, JAPAN. NCI, USN, MED ONCOL BRANCH, NATL NAVAL MED CTR, BETHESDA, MD 20889 USA. FU NCI NIH HHS [CA35299]; NIGMS NIH HHS [GM50819] NR 46 TC 121 Z9 125 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD APR 11 PY 1997 VL 272 IS 15 BP 9979 EP 9985 DI 10.1074/jbc.272.15.9979 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WU039 UT WOS:A1997WU03900057 PM 9092538 ER PT J AU Rein, T Natale, DA Gartner, U Niggemann, M DePamphilis, ML Zorbas, H AF Rein, T Natale, DA Gartner, U Niggemann, M DePamphilis, ML Zorbas, H TI Absence of an unusual ''densely methylated island'' at the hamster dhfr ori-beta SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA METHYLTRANSFERASE; 5-METHYLCYTOSINE RESIDUES; REPLICATION; GENE; PROTEIN; 5-METHYLDEOXYCYTIDINE; DEMETHYLATION; POLYMERASE; INITIATION; FRAGMENTS AB An unusual ''densely methylated island'' (DMI), in which all cytosine residues are methylated on both strands for 127-516 base pairs, has been reported at mammalian origins of DNA replication. This report had far-reaching implications in understanding of DNA methylation and DNA replication. For example, since this DMI appeared in about 90% of proliferating cells, but not in stationary cells, it may regulate origin activation. In an effort to confirm and extend these observations, the DMI at the well characterized ori-beta locus 17 kilobases downstream of the dhfr gene in chromosomes of Chinese hamster ovary cells was checked for methylated cytosines in genomic DNA. The methylation status of this region was examined in randomly proliferating and stationary cells and in cell populations enriched in the G(1), S, or G(2) + M phases of their cell division cycle. DNA was subjected to 1) cleavage by methylation-sensitive restriction endonucleases, 2) hydrazine modification of cytosines followed by piperidine cleavage, and 3) permanganate modification of 5-methylcytosines (C-m) followed by piperidine cleavage. The permanganate reaction is a novel method for direct detection of C-m residues that complements the more commonly used hydrazine method. These methods were capable of detecting C-m in 2% of the cells. At the region of the proposed DMI, only one mC at a CpG site was detected. However, the ori-beta DMI was not detected in any of these cell populations using any of these methods. C1 UNIV MUNICH,INST BIOCHEM,D-81377 MUNICH,GERMANY. NICHHD,NIH,BETHESDA,MD 20892. NR 44 TC 21 Z9 23 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 APR 11 PY 1997 VL 272 IS 15 BP 10021 EP 10029 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WU039 UT WOS:A1997WU03900063 PM 9092544 ER PT J AU Yuan, Y Crane, DC Musser, JM Sreevatsan, S Barry, CE AF Yuan, Y Crane, DC Musser, JM Sreevatsan, S Barry, CE TI MMAS-1, the branch point between cis- and trans-cyclopropane-containing oxygenated mycolates in Mycobacterium tuberculosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-LACTAM ANTIBIOTICS; MYCOLIC ACID PATTERNS; CELL-WALL; IDENTIFICATION; CHELONAE; CHROMATOGRAPHY; PERMEABILITY; BIOSYNTHESIS; RESISTANCE; SMEGMATIS AB The proportion of mycolic acid containing trans-substituents at the proximal position of the meromycolate chain is an important determinant of fluidity of the mycobacterial cell wall and is directly related to the sensitivity of mycobacterial species to hydrophobic antibiotics. MMAS-1, an enzyme encoded in the gene cluster responsible for the biosynthesis of methoxymycolates, was overexpressed in Mycobacterium tuberculosis and shown to result in the overproduction of trans-cyclopropane and trans-olefin-containing oxygenated mycolic acids. MMAS-1 converted a cis-olefin into a trans-olefin with concomitant introduction of an allylic methyl branch in a precursor to both the methoxy and ketone-containing mycolic acids. In addition to an increase in the amount of trans-mycolate, MMAS-1 expression resulted in a substantial increase in the amount of ketomycolate produced relative to methoxymycolate. Thus MMAS-1 may act at a complex branch point where expression of this enzyme directly affects the cis- to trans-ratio and indirectly affects the keto to methoxy ratio. Overexpression of MMAS-1 resulted in a substantially slower growth rate at moderately elevated temperature, decreased thermal stability of the cell wall as measured by differential scanning calorimetry, and an increased permeability to chenodeoxycholate. These results provide experimental evidence for the intermediacy of trans-olefinic mycolate precursors in trans-cyclopropane formation and suggest that increasing the proportion of the polar ketomycolate subclass may exert a significant fluidizing effect on the cell wall. C1 NIAID,ROCKY MT LABS,TB RES UNIT,LAB INTRACELLULAR PARASITES,NIH,HAMILTON,MT 59840. BAYLOR COLL MED,DEPT PATHOL,SECT MOL PATHOBIOL,HOUSTON,TX 77030. RI Barry, III, Clifton/H-3839-2012; OI Sreevatsan, Srinand/0000-0002-5162-2403 FU Intramural NIH HHS [Z01 AI000783-11]; NIAID NIH HHS [AI-37004]; NIDA NIH HHS [DA-09238] NR 37 TC 67 Z9 72 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 APR 11 PY 1997 VL 272 IS 15 BP 10041 EP 10049 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WU039 UT WOS:A1997WU03900066 PM 9092547 ER PT J AU Zhao, H Neamati, N Mazumder, A Sunder, S Pommier, Y Burke, TR AF Zhao, H Neamati, N Mazumder, A Sunder, S Pommier, Y Burke, TR TI Arylamide inhibitors of HIV-1 integrase SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; KINASE INHIBITORS; PROTEIN; INVITRO AB Based on data derived from a large number of HIV-1 integrase inhibitors, similar structural features can be observed, which consist of two aryl units separated by a central linker. For many inhibitors fitting this pattern, at least one aryl ring also requires ortho bis-hydroxylation for significant inhibitory potency. The ability of such catechol species to undergo in situ oxidation to reactive quinones presents one potential limitation to their utility. In an effort to address this problem, a series of inhibitors were prepared which did not contain ortho bis-hydroxyls. None of these analogues exhibited significant inhibition. Therefore an alternate approach was taken, whose aim was to increase potency rather than eliminate catechol substructures. In this latter study, naphthyl nuclei were utilized as aryl components, since a previous report had indicated that fused bicyclic rings may afford higher affinity relative to monocyclic phenyl-based systems. In preliminary work with monomeric units, it was found that the 6,7-dihydroxy-2-naphthoic acid (17) (IC50 = 4.7 mu M) was approximately 10-fold more potent than its 5,6-dihydroxy isomer 19 (IC50 = 62.4 mu M). Of particular note was the dramatic difference in potency between free acid 17 and its methyl ester 21 (IC50 > 200 mu M). The nearly total loss of activity induced by esterification strongly indicates that the free carboxylic -OH is important for high potency of this compound. This contrasts with the isomeric 5,6-dihydroxy species 19, where esterification had no effect on inhibitory potency (23, IC50 = 52.7 mu M). These data provide evidence that the monomeric 6,7- and 5,6-dihydroxynaphthalenes may be interacting with the enzyme in markedly different fashions. However, when these naphthyl nuclei were incorporated into dimeric structures, significant enhancements in potencies each relative to the monomeric acids were observed, with bis-6,7-dihydroxy analogue 49 and bis-5,6-dihydroxy analogue 51 both exhibiting approximately equal potencies (IC50 values of 0.81 and 0.11 mu M, respectively). C1 NCI,MED CHEM LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. RI Burke, Terrence/N-2601-2014 NR 22 TC 89 Z9 93 U1 1 U2 3 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 APR 11 PY 1997 VL 40 IS 8 BP 1186 EP 1194 DI 10.1021/jm960449w PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA WT794 UT WOS:A1997WT79400002 PM 9111292 ER PT J AU Xiao, W Li, GY Maitra, RK Maran, A Silverman, RH Torrence, PF AF Xiao, W Li, GY Maitra, RK Maran, A Silverman, RH Torrence, PF TI Correlation of selective modifications to a 2',5'-oligoadenylate-3',5'-deoxyribonucleotide antisense chimera with affinity for the target nucleic acid and with ability to activate RNase L SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID THERAPEUTIC AGENTS; 2-5A ANTISENSE; OLIGONUCLEOTIDES; INTERFERON; BASE AB The use of an antisense oligonucleotide to address a specific targeted RNA sequence and subsequent localized activation of the 2-5A-dependent RNase (RNase L) to effect selective RNA degradation is a new approach to the control of gene expression called 2-5A-antisense. The previously reported biological activity of the 2-5A:AS chimeric oligonucleotide [p5'(A2'p)(3)A-antiPKR1], directed against nucleotides 55-73 of the coding sequence of the PKR mRNA, has been used as a point of reference to examine the effect of introducing mismatches into the chimeric oligonucleotide, altering the chain length of the antisense domain of the chimeras, removal of the 5'-monophosphate moiety, shortening the 2',5'-oligoadenylate domain, and substitution of 3',5'-linked 2'-deoxyadenosine nucleotides for the 2-5A domain. The general formula for the novel chimeric oligonucleotides is p5'(A2'p)(3)A2'p(CH2)(4)p(CH2)(4)p(5'N3'p)(m)N, where N is any nucleoside and m is any integer. When the biological activity of these new chimeric oligonucleotides was compared to that of the parent chimera, 2-5A-aPKR, for their ability to effect target PKR RNA cleavage in a cell-free and in an intact cell assay, it was determined that there was a close correlation between the activity of 2-5A-antisense chimeras and their affinity (T-m) for a targeted nucleic acid. In addition, there was also a close correlation between activity of the 2-5A-antisense chimeras and their ability to activate the 2-5A-dependent RNase L. C1 NIDDK,SECT BIOMED CHEM,MED CHEM LAB,NIH,BETHESDA,MD 20892. CLEVELAND CLIN FDN,RES INST,NN1 06,DEPT CANC BIOL,CLEVELAND,OH 44195. FU NCI NIH HHS [1 PO1 CA62220] NR 22 TC 12 Z9 12 U1 0 U2 3 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 APR 11 PY 1997 VL 40 IS 8 BP 1195 EP 1200 DI 10.1021/jm960748l PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA WT794 UT WOS:A1997WT79400003 PM 9111293 ER PT J AU Chang, AC Burgess, JP Mascarella, SW Abraham, P Kuhar, MJ Carroll, FI AF Chang, AC Burgess, JP Mascarella, SW Abraham, P Kuhar, MJ Carroll, FI TI Synthesis and transporter binding properties of 2,3-diphenyltropane stereoisomers. Comparison to 3 beta-phenyltropane-2 beta-carboxylic acid esters SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID NOREPINEPHRINE TRANSPORTERS; DOPAMINE TRANSPORTER; COCAINE RECEPTOR; HIGH-AFFINITY; ANALOGS; SEROTONIN; SPECTROSCOPY; INHIBITION; SITES; PHASE AB 2 beta,3 beta-Diphenyl-(5), 2 alpha,3 alpha-diphenyl-(6), and 2 alpha,3 beta-diphenyltropane (3) as well as 2,3-diphenyltrop-2-ene (4) were prepared in racemic form and assayed for inhibition of radioligand binding at the dopamine (DA), serotonin (5-HT), and norepinephrine (NE) transporters. Among all three transporters, compounds 4-6 bound the DA transporter with the highest affinity. The 2 beta,3 beta-diphenyltropane (5) bound the DA transporter with an IC50 value (28 nM) almost identical to that of 3 beta-phenyltropane-2 beta-carboxylic acid methyl ester (WIN 35,065-2) and has much greater selectivity relative to binding to the serotonin transporter. A comparison of the radioligand data from this study to radioligand data obtained on other WIN 35,065-2 analogs suggests that hydrophobicity of the C-2 substituent of some analogs of the WIN 35,065-2 class may be an important contributing factor to binding at the DA transporter. C1 RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NIDA,NEUROSCI BRANCH,ADDICT RES CTR,BALTIMORE,MD 21224. OI Mascarella, Wayne/0000-0003-0092-8178 FU NIDA NIH HHS [DA05477] NR 28 TC 18 Z9 18 U1 1 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 APR 11 PY 1997 VL 40 IS 8 BP 1247 EP 1251 DI 10.1021/jm960703k PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA WT794 UT WOS:A1997WT79400008 PM 9111298 ER PT J AU Gopalan, V Baxevanis, AD Landsman, D Altman, S AF Gopalan, V Baxevanis, AD Landsman, D Altman, S TI Analysis of the functional role of conserved residues in the protein subunit of ribonuclease P from Escherichia coli SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE RNase P protein subunit; site-directed mutagenesis ID RNA-BINDING DOMAIN; 4.5 S-RNA; CRYSTAL-STRUCTURE; SEQUENCE; INVITRO; MUTANTS; EXPRESSION; HOLOENZYME; ALIGNMENT; PRECURSOR AB The processing of precursor tRNAs and some other small cellular RNAs by M1 RNA, the catalytic subunit of Escherichia coli ribonuclease P, is accelerated by C5 protein (the protein cofactor) both in vitro and in vivo. In an effort to understand the mechanism by which the protein cofactor promotes and stabilizes certain conformations of M1 RNA that are most efficient for RNase P catalysis, we have used site-directed mutagenesis to generate mutant derivatives of C5 protein and assessed their ability to promote RNase P catalysis in vivo and in vitro. Our results indicate that certain conserved hydrophobic and basic residues in C5 protein are important for its function and that single amino acid residue changes in C5 protein can alter the substrate specificity of the RNase P holoenzyme. (C) 1997 Academic Press Limited. C1 YALE UNIV, DEPT BIOL, NEW HAVEN, CT 06520 USA. NIH, NATL CTR BIOTECHNOL INFORMAT, NATL LIB MED, BETHESDA, MD 20894 USA. RI Landsman, David/C-5923-2009; OI Landsman, David/0000-0002-9819-6675 FU NIGMS NIH HHS [GM19422] NR 39 TC 65 Z9 66 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD APR 11 PY 1997 VL 267 IS 4 BP 818 EP 829 DI 10.1006/jmbi.1997.0906 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WU200 UT WOS:A1997WU20000006 PM 9135114 ER PT J AU Zetterstrom, RH Solomin, L Jansson, L Hoffer, BJ Olson, L Perlmann, T AF Zetterstrom, RH Solomin, L Jansson, L Hoffer, BJ Olson, L Perlmann, T TI Dopamine neuron agenesis in Nurr1-deficient mice SO SCIENCE LA English DT Article ID NEUROTROPHIC FACTOR; BRAIN; DEHYDROGENASE; NURR1; BDNF AB Dopamine neurons of the substantia nigra and ventral tegmental area regulate movement and affective behavior and degenerate in Parkinson's disease. The orphan nuclear receptor Nurr1 was shown to be expressed in developing dopamine neurons before the appearance of known phenotypic markers for these cells. Mice lacking Nurr1 failed to generate midbrain dopaminergic neurons, were hypoactive, and died soon after birth, Nurr1 expression continued into adulthood, and brains of heterozygous animals, otherwise apparently healthy, contained reduced dopamine levels. These results suggest that putative Nurr1 ligands may be useful for treatment of Parkinson's disease and other disorders of midbrain dopamine circuitry. C1 LUDWIG INST CANC RES,STOCKHOLM BRANCH,S-17177 STOCKHOLM,SWEDEN. KAROLINSKA INST,DEPT NEUROSCI,S-17177 STOCKHOLM,SWEDEN. NIDA,INTRAMURAL RES PROGRAM,NIH,BALTIMORE,MD 21224. NR 34 TC 720 Z9 751 U1 0 U2 16 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD APR 11 PY 1997 VL 276 IS 5310 BP 248 EP 250 DI 10.1126/science.276.5310.248 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WT925 UT WOS:A1997WT92500043 PM 9092472 ER PT J AU Carroll, RG Riley, JL Levine, BL Feng, Y Kaushal, S Ritchey, DW Bernstein, W Weislow, OS Brown, CR Berger, EA June, CH StLouis, DC AF Carroll, RG Riley, JL Levine, BL Feng, Y Kaushal, S Ritchey, DW Bernstein, W Weislow, OS Brown, CR Berger, EA June, CH StLouis, DC TI Differential regulation of HIV-1 fusion cofactor expression by CD28 costimulation of CD4(+) T cells SO SCIENCE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MOLECULAR-CLONING; MONOCLONAL-ANTIBODIES; CROSS-LINKING; HUMAN HOMOLOG; NPY BINDING; ACTIVATION; RECEPTOR; GENE; RESPONSES AB Activation of CD4(+) T lymphocytes from human immunodeficiency virus-type 1 (HIV-1)-infected donors with immobilized antibodies to CD3 and CD28 induces a virus-resistant state. This effect is specific for macrophage-tropic HIV-I, Transcripts encoding CXCR4/Fusin, the fusion cofactor used by T cell line-tropic isolates, were abundant in CD3/CD28-stimulated cells, but transcripts encoding CCR5, the fusion cofactor used by macrophage-tropic viruses, were not detectable. Thus, CD3/CD28 costimulation induces an HIV-1-resistant phenotype similar to that seen in some highly exposed and HIV-uninfected individuals. C1 HENRY M JACKSON FDN ADVANCEMENT MIL MED,ROCKVILLE,MD 20850. USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20889. WALTER REED ARMY INST RES,DIV RETROVIROL,ROCKVILLE,MD 20850. NIAID,VIRAL DIS LAB,NIH,BETHESDA,MD 20889. SRA TECHNOL,ROCKVILLE,MD 20850. NIAID,INFECT DIS LAB,NIH,ROCKVILLE,MD 20852. RI Levine, Bruce/D-1688-2009 NR 51 TC 159 Z9 160 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD APR 11 PY 1997 VL 276 IS 5310 BP 273 EP 276 DI 10.1126/science.276.5310.273 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WT925 UT WOS:A1997WT92500051 PM 9092480 ER PT J AU Glushakova, S Baibakov, B Zimmerberg, J Margolis, LB AF Glushakova, S Baibakov, B Zimmerberg, J Margolis, LB TI Experimental HIV infection of human lymphoid tissue: Correlation of CD4(+) T cell depletion and virus syncytium-inducing/non-syncytium-inducing phenotype in histocultures inoculated with laboratory strains and patient isolates of HIV type 1 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; FOLLICULAR DENDRITIC CELLS; THYMIC ORGAN-CULTURE; PBL-SCID MICE; DOWN-REGULATION; ANIMAL-MODELS; AIDS; PATHOGENESIS; LYMPHADENOPATHY; GLYCOPROTEIN AB It is now apparent that HIV infection leads to a gradual collapse of a complex system of lymphoid tissue, This collapse tends to be associated with a change in virus tropism from macrophages to T lymphocytes, and a change in phenotype from nonsyncytium inducing (NSI) to syncytium inducing (SI). An experimental system is required to study the role of this change in HIV pathogenesis in lymphoid tissue, Here we describe such a system, Histocultures of human lymphoid tissue preserve their general cytoarchitecture, including a network of follicular dendritic cells (FDCs), Histocultures of tonsils, adenoids, or lymph nodes support productive infection with various laboratory and primary isolates of HIV-1 of different tropism and phenotype and exhibit isolate-dependent CD4(+) T lymphocyte depletion, A strong correlation between the extent of CD4(+) T cell depletion and the SI/NSI phenotype of the isolates is demonstrated, AZT was used as a model drug to inhibit viral replication and CD4(+) T cell depletion in lymphoid histocultures. HIV pathogenesis and the effect of antivirals can now be studied in human lymphoid tissue under controlled conditions in vitro. C1 NICHHD,LAB CELLULAR & MOL BIOPHYS,NIH,BETHESDA,MD 20892. NICHHD,NASA,CTR THREE DIMENS TISSUE CULTURE,NIH,BETHESDA,MD 20892. NR 52 TC 78 Z9 78 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR 10 PY 1997 VL 13 IS 6 BP 461 EP 471 DI 10.1089/aid.1997.13.461 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA WT421 UT WOS:A1997WT42100003 PM 9100987 ER PT J AU Ostrowski, MA Stanley, SK Justement, JS Gantt, K Goletti, D Fauci, AS AF Ostrowski, MA Stanley, SK Justement, JS Gantt, K Goletti, D Fauci, AS TI Increased in vitro tetanus-induced production of HIV type 1 following in vivo immunization of HIV type 1-infected individuals with tetanus toxoid SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL ACTIVATION; IMMUNE ACTIVATION; INFECTION; LYMPHOCYTES; REPLICATION; AIDS AB We have previously demonstrated that immunization of HIV-l-infected individuals with the common recall antigen, tetanus, induced transient increases in plasma viremia as well as an increased ability to isolate virus from CD8(+) T cell-depleted peripheral blood mononuclear cells (PBMCs) under minimally stimulated culture conditions (IL-2 plus IL-4) postimmunization, In this study, HIV-l-infected individuals were immunized with tetanus toroid and PBMCs were examined at multiple time points following immunization, Tetanus-induced production of virus was defined as an increased ability to isolate HIV-1 from CD8(+) T cell-depleted PBMCs in vitro in the presence of tetanus antigen as opposed to no antigen or control antigen alone, Following immunization, in vitro tetanus-induced production of HIV-1 was observed in 8 of 13 (62%) patients compared to 2 of 13 (15%) patients prior to immunization. In four of these patients, virus could also be isolated from CD8(+) T cell-depleted PBMCs in the presence of tetanus without the addition of any exogenous IL-2, Furthermore, virus could be isolated from the unfractionated PBMCs of two patients when tetanus antigen alone was added to the culture in the absence of added PHA or PHA blasts, HIV-1 was isolated predominantly from CD4(+) T cells with a CD45RO(+), CD25(+) phenotype and was associated with a trend to elevated levels in culture supernatants of IFN-gamma, IL-6, TNF-alpha, and IL-4. These findings have important implications with regard to the role of ongoing antigen-specific immune responses in the induction of HIV-1 expression in vivo. RP Ostrowski, MA (reprint author), NIAID,IMMUNOREGULAT LAB,NIH,BLDG 10,ROOM 6A11,10 CTR DR,MSC 1576,BETHESDA,MD 20892, USA. OI Goletti, Delia/0000-0001-8360-4376 NR 26 TC 25 Z9 25 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 APR 10 PY 1997 VL 13 IS 6 BP 473 EP 480 DI 10.1089/aid.1997.13.473 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA WT421 UT WOS:A1997WT42100004 PM 9100988 ER PT J AU Hu, HH Stavrou, S Baker, BC Tornatore, C Scharff, J Okunieff, P Neville, DM AF Hu, HH Stavrou, S Baker, BC Tornatore, C Scharff, J Okunieff, P Neville, DM TI Depletion of T lymphocytes with immunotoxin retards the progress of experimental allergic encephalomyelitis in rhesus monkeys SO CELLULAR IMMUNOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MYELIN BASIC-PROTEIN; CENTRAL-NERVOUS-SYSTEM; MONOCLONAL-ANTIBODIES; MULTIPLE-SCLEROSIS; DIPHTHERIA-TOXIN; LEWIS RATS; CELLS; IDENTIFICATION; MACROPHAGES AB FN18-CRM9 is an anti-rhesus anti-CD3 immunotoxin that call transiently deplete T cells to 1% of initial values in both the blood and lymph node compartments and can induce long-term tolerance to mismatched renal allografts. We have investigated the ability of this immunotoxin to interdict the course of an experimental rhesus T-cell-driven autoimmune disease, experimental allergic encephalomyelitis (EAE) induced by myelin basic protein. Monkeys showing CSF pleocytosis were then treated with FN18-CRM9 alone or in combination with cranial irradiation (325 or 650 cGy). EAE in nontreated control monkeys progressed rapidly. Paralysis occurred 4-6 days after CSF pleocytosis. Paralysis was either delayed or never occurred in treated monkeys, and histopathology revealed few inflammatory plaques that were notable for their low or absent T cell content. While T cells repopulate ill the periphery posttreatment, they do not return to the CNS in large numbers, suggesting that the newly repopulated T cells have lost their previously acquired CNS homing capability. Anti-CD3 immunotoxin may be useful in treating clinical T-cell-driven autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. C1 NIMH,SECT BIOPHYS CHEM,MOL BIOL LAB,NIH,BETHESDA,MD 20892. NINCDS,MOL THERAPEUT SECT,MOL MED LAB,NIH,BETHESDA,MD 20892. NCI,RADIAT ONCOL BRANCH,NIH,BETHESDA,MD 20892. NR 33 TC 22 Z9 26 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD APR 10 PY 1997 VL 177 IS 1 BP 26 EP 34 DI 10.1006/cimm.1997.1096 PG 9 WC Cell Biology; Immunology SC Cell Biology; Immunology GA WW325 UT WOS:A1997WW32500004 PM 9140093 ER PT J AU Nelson, DM Metzger, ME Donahue, RE Morgan, RA AF Nelson, DM Metzger, ME Donahue, RE Morgan, RA TI In vivo retrovirus-mediated gene transfer into multiple hematopoietic lineages in rabbits without preconditioning SO HUMAN GENE THERAPY LA English DT Article ID LONG-TERM ENGRAFTMENT; STEM-CELL FACTOR; BONE-MARROW; PERIPHERAL-BLOOD; PROGENITOR CELLS; MURINE MARROW; IN-VITRO; TRANSDUCTION; EXPRESSION; VECTORS AB Hematopoietic progenitor cells are attractive targets for gene therapy of inherited and acquired disorders, We have developed a novel procedure for mediating gene transfer into hematopoietic cells using an in vivo approach, The procedure involves injection of irradiated retroviral producer cells into the femoral bone marrow cavity in rabbits without preconditioning, The emergence of vector-marked cells in multiple peripheral blood hematopoietic lineages was detected 1 week post-injection and persisted until the animals were sacrificed up to 20 months later, Vector-marked cells were also detected in different hematopoietic tissues including bone marrow, spleen, thymus, and lymph node, Expression of retrovirus-specific messages by reverse transcription polymerase chain reaction was detected at multiple time points up to 20 months. Retrovirally encoded protein was detected by enzyme-linked immunosorbent assay in supernatant from cultures of granulocytes isolated 14 months after the procedure, This work demonstrates the feasibility of effecting gene transfer into hematopoietic progenitor cells in vivo. C1 NIH,NATL CTR HUMAN GENOME RES,CLIN GENE THERAPY BRANCH,GENE TRANSFER TECHNOL SECT,BETHESDA,MD 20892. NHLBI,NIH,BETHESDA,MD 20892. NR 25 TC 18 Z9 18 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD APR 10 PY 1997 VL 8 IS 6 BP 747 EP 754 DI 10.1089/hum.1997.8.6-747 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WV381 UT WOS:A1997WV38100009 PM 9113514 ER PT J AU Youngs, SJ Ali, SA Taub, DD Rees, RC AF Youngs, SJ Ali, SA Taub, DD Rees, RC TI Chemokines induce migrational responses in human breast carcinoma cell lines SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID SIGNAL-TRANSDUCTION; CANCER; MOTILITY; INVASIVENESS; METASTASIS; PROTEIN-1; RECEPTORS; INVASION; GENE AB Chemokines have been shown to chemoattract and activate different leukocyte populations, Here we report the in vitro effect of macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, regulated on activation, normal T-cells, expressed and secreted (RANTES), monocyte chemotactic protein-1 (MCP-1), interleukin-8 (IL-8), interferon inducible protein-10 (IP-IO), neutrophil-activating peptide-2 (NAP-2), growth-related protein (GRO)-alpha and GRO-gamma, on the migration of 3 human breast carcinoma cell lines, MCF-7, T47D and ZR-75-1, using a microchemotaxis chamber to assess migration across fibronectin-coated polycarbonate membranes. MCF-7 cells responded chemotactically to all chemokines tested in a pattern which was dose and time dependent, although responses to the different chemokines were variable. ZR-75-1 responded to MIP-1 beta and GRO-alpha, giving maximum migration indices of 3.7 and 5.3, respectively, and exhibited a migratory response to MIP-1 alpha, IL-8 and MCP-I although to a lower degree, T47D was unresponsive to the chemokines tested, but both MCF-7 and T47D cells bound radiolabelled ligands with binding constants (Kd) ranging from 0.6 to 2.2 nM and 0.6 to 2.1 nM, respectively. The specificity of the chemotactic response of MCF-7 to MIP-1 alpha and MIP-1 beta was confirmed using chemokine-specific neutralising antibodies and heat denaturation, and was demonstrated to involve G protein and cyclic AMP signalling pathways. MIP-1 beta and MIP-1 alpha were shown to induce changes in the organisation of the actin cytoskeleton and the level of F-actin in MCF-7 cells, as determined using flow cytometric analysis and confocal microscopy, Our results show that breast carcinoma cells can respond to chemokines, and suggests a potential role for these molecules in the process of tumour cell migration, invasion and metastasis. (C) 1997 Wiley-Liss, Inc. C1 NOTTINGHAM TRENT UNIV,DEPT LIFE SCI,NOTTINGHAM NG1 4BU,ENGLAND. NCI,CLIN SERV PROGRAM,FCRDC,FREDERICK,MD 21701. RP Youngs, SJ (reprint author), UNIV SHEFFIELD,SCH MED,INST CANC STUDIES,BEECH HILL RD,SHEFFIELD S10 2RX,S YORKSHIRE,ENGLAND. NR 23 TC 156 Z9 164 U1 0 U2 9 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 10 PY 1997 VL 71 IS 2 BP 257 EP 266 DI 10.1002/(SICI)1097-0215(19970410)71:2<257::AID-IJC22>3.0.CO;2-D PG 10 WC Oncology SC Oncology GA WW905 UT WOS:A1997WW90500022 PM 9139852 ER PT J AU Bruno, JM Feachmen, R Godal, T Nchinda, T Ogilvie, B Mons, B Mshana, R Radda, G Samba, E Schwartz, M Varmus, H Diallo, S Doumbo, O Greenwood, B Kilama, W Miller, LH daSilva, LP AF Bruno, JM Feachmen, R Godal, T Nchinda, T Ogilvie, B Mons, B Mshana, R Radda, G Samba, E Schwartz, M Varmus, H Diallo, S Doumbo, O Greenwood, B Kilama, W Miller, LH daSilva, LP TI The spirit of Dakar: A call for action on malaria SO NATURE LA English DT Letter C1 NIAID,NIH,BETHESDA,MD 20892. WORLD BANK,WASHINGTON,DC 20433. WELLCOME TRUST RES LABS,LONDON,ENGLAND. WHO,TDR,GENEVA,SWITZERLAND. NETHERLANDS ORG SCI RES,THE HAGUE,NETHERLANDS. MRC,LONDON W1N 4AL,ENGLAND. MRC,BRAZZAVILLE,CONGO. INST PASTEUR,PARIS,FRANCE. NR 0 TC 18 Z9 18 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 APR 10 PY 1997 VL 386 IS 6625 BP 541 EP 541 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WT273 UT WOS:A1997WT27300023 PM 9121571 ER PT J AU Courtney, SM Ungerleider, BG Keil, K Haxby, JV AF Courtney, SM Ungerleider, BG Keil, K Haxby, JV TI Transient and sustained activity in a distributed neural system for human working memory SO NATURE LA English DT Article ID SHORT-TERM-MEMORY; PREFRONTAL CORTEX; TEMPORAL CORTEX; FRONTAL-CORTEX; NEURONS; TASK; DISSOCIATION; ACTIVATION AB Working memory involves the short-term maintenance of an active representation of information so that it is available for further processing. Visual working memory tasks, in which subjects retain the memory of a stimulus over brief delays, require both the perceptual encoding of the stimulus and the subsequent maintenance of its representation after the stimulus is removed from view. Such tasks activate multiple areas in visual and prefrontal cortices(1-9). To delineate the roles these areas play in perception and working memory maintenance, we used functional magnetic resonance imaging (fMRI) to obtain dynamic measures of neural activity related to different components of a face working memory task-non-selective transient responses to visual stimuli, selective transient responses to faces, and sustained responses over memory delays. Three occipitotemporal areas in the ventral object vision pathway had mostly transient responses to stimuli, indicating their predominant role in perceptual processing, whereas three prefrontal areas demonstrated sustained activity over memory delays, indicating their predominant role in working memory. This distinction, however, was not absolute. Additionally, the visual areas demonstrated different degrees of selectivity, and the prefrontal areas demonstrated different strengths of sustained activity, revealing a continuum of functional specialization, from occipital through multiple prefrontal areas, regarding each area's relative contribution to perceptual and mnemonic processing. C1 NATL INST HLTH,SECT NEUROCIRCUITRY,LAB BRAIN & COGNIT,BETHESDA,MD 20892. RP Courtney, SM (reprint author), NATL INST HLTH,SECT FUNCT BRAIN IMAGING,10 CTR DR,MSC 1366,BETHESDA,MD 20892, USA. NR 30 TC 627 Z9 648 U1 4 U2 32 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD APR 10 PY 1997 VL 386 IS 6625 BP 608 EP 611 DI 10.1038/386608a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WT273 UT WOS:A1997WT27300059 PM 9121584 ER PT J AU Brown, KE Tisdale, J Barrett, AJ Dunbar, CE Young, NS AF Brown, KE Tisdale, J Barrett, AJ Dunbar, CE Young, NS TI Hepatitis-associated aplastic anemia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BONE-MARROW TRANSPLANTATION; SUPPRESSOR LYMPHOCYTES-T; NON-A; NON-B; ANTITHYMOCYTE GLOBULIN; LIVER-TRANSPLANTATION; VIRAL-HEPATITIS; GENE-EXPRESSION; FAILURE; CYCLOSPORINE AB Background Hepatitis-associated aplastic anemia is a variant of aplastic anemia in which aplastic anemia follows an acute attack of hepatitis. The aplastic anemia, however, is often fatal if untreated. To characterize the illness, investigate the role of hepatitis viruses, and assess the response to immunosuppressive treatment, we studied patients with the syndrome who were referred to the National Institutes of Health (NIH). Methods Standard hematologic and biochemical tests and measurements of bone marrow cellularity were used to monitor the patients' response to treatment. Serum was assayed for antibodies and antigens related to hepatitis A, B, and C viruses and for the RNA of hepatitis C and GB virus C by the polymerase chain reaction. All patients were treated with antithymocyte globulin and cyclosporine. Results Ten patients with hepatitis-associated aplastic anemia were referred to the NIH between 1990 and 1996; all had the typical features of this syndrome. There was evidence of activated CD8 T lymphocytes in the blood. Serologic tests for hepatitis A, B, and C viruses were negative; RNA of hepatitis C virus was undetectable in all patients, but RNA of GB virus C was detected in three patients. Seven of the patients responded to intensive immunosuppressive treatment; the three who did not respond all died within one year of treatment, two from complications of stem-cell or marrow transplantation. Conclusions The hepatitis of the hepatitis-associated aplastic anemia does not appear to be caused by any of the known hepatitis viruses. We recommend immunosuppressive treatment for patients who do not have an HLA-matched related donor available for bone marrow transplantation. Several features of the syndrome suggest that it is mediated by immunopathologic mechanisms. (C) 1997, Massachusetts Medical Society. RP Brown, KE (reprint author), NHLBI,HEMATOL BRANCH,NIH,BLDG 10,RM 7C218,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 37 TC 151 Z9 162 U1 0 U2 3 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 10 PY 1997 VL 336 IS 15 BP 1059 EP 1064 DI 10.1056/NEJM199704103361504 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA WT161 UT WOS:A1997WT16100004 PM 9091802 ER PT J AU Isaacs, JS Chen, PC Garza, A Hansen, MF Barrett, JC Weissman, BE AF Isaacs, JS Chen, PC Garza, A Hansen, MF Barrett, JC Weissman, BE TI Failure of HPV E6 to rapidly degrade p53 in human HeLa x PNET cell hybrids SO ONCOGENE LA English DT Article DE p53; E6; tumor suppressor genes ID HUMAN PAPILLOMAVIRUS TYPE-16; WILD-TYPE P53; MAMMARY EPITHELIAL-CELLS; GENE-MUTATIONS; HUMAN KERATINOCYTES; IN-VITRO; PROTEIN; EXPRESSION; UBIQUITIN; TUMOR AB The ability of the E6 protein from high risk human papillomaviruses (HPVs) to degrade p53 via the ubiquitin pathway plays a major role in the development of cervical carcinomas. We have previously generated cell hybrids between a p53 null peripheral neuroepithelioma (PNET) cell line and a cervical carcinoma HeLa cell line which exhibits efficient E6-mediated degradation of p53. All of the resulting hybrids expressed HPV 18 E6 from the HeLa parent and some of the hybrids additionally expressed HPV 16 E6. Surprisingly, in spite of abundant E6 expression, the hybrids expressed relatively high steady-state levels of the wild-type p53 protein. We then examined the hybrids to determine whether other components of the E6-mediated degradation pathway were missing or nonfunctional. Specifically, we determined that the E6-associated protein (E6-AP), essential for E6-mediated degradation, was expressed. We further verified that these hybrids had a functional ubiquitination pathway, which suggests that this phenomenon is not due to a general defect in this pathway. We therefore conclude that other unidentified, possibly cell-specific factors can play a role in the E6-mediated degradative process and may act to inhibit this process. C1 UNIV N CAROLINA,DEPT BIOCHEM & BIOPHYS,CHAPEL HILL,NC 27599. UNIV N CAROLINA,LINEBERGER COMPREHENS CANC CTR,CHAPEL HILL,NC 27599. BOSTON UNIV,SCH MED,CTR HUMAN GENET,BOSTON,MA 02118. NATL INST ENVIRONM HLTH SCI,MOL CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. FU NCI NIH HHS [CA 53318, CA 60122, CA 44470] NR 67 TC 11 Z9 11 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 10 PY 1997 VL 14 IS 14 BP 1669 EP 1678 DI 10.1038/sj.onc.1201001 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA WR893 UT WOS:A1997WR89300005 PM 9135068 ER PT J AU King, C Eisenberg, E Greene, L AF King, C Eisenberg, E Greene, L TI Effect of yeast and human DnaJ homologs on clathrin uncoating by 70 kilodalton heat shock protein SO BIOCHEMISTRY LA English DT Article ID ESCHERICHIA-COLI DNAJ; COATED VESICLES; ATPASE ACTIVITY; ENDOPLASMIC-RETICULUM; SUBSTRATE-BINDING; BACTERIAL DNAJ; HSP70; CHAPERONE; GRPE; TRANSLOCATION AB We recently found that the DnaJ homolog auxilin is required for Hsc70 to uncoat clathrin baskets. In the present study, we investigated the effect of two other DnaJ homologs, YDJ1 from yeast and HDJ1 from humans, on the uncoating activity of Hsc70. Neither YDJ1 nor HDJ1 substituted for auxilin in supporting uncoating. Rather, in the presence of auxilin, both YDJ1 and HDJ1 strongly inhibited uncoating at pH 7 and also prevented the binding of Hsc70 to clathrin baskets at pH 6. Both YDJ1, as shown previously, and HDJ1 catalytically induce polymerization of Hsc70 into large polymers in ATP, and the YDJ1 concentration required to inhibit uncoating was similar to the concentration required for polymerization. However, uncoating was almost completely inhibited even at low concentrations of Hsc70 where only partial polymerization occurs, suggesting that YDJ1 inhibits uncoating not only by polymerizing the Hsc70 but also by some other mechanism as well. The effects of YDJ1 and HDJ1 were completely reversible; when they were removed, the Hsc70 regained full activity. Since both YDJ1 and HDJ1 inhibited the uncoating of clathrin baskets by brain cytosol as well as by purified Hsc7O, this could be a physiological phenomenon which could affect other activities of Hsc70 in addition to uncoating. C1 NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. NR 46 TC 16 Z9 17 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 8 PY 1997 VL 36 IS 14 BP 4067 EP 4073 DI 10.1021/bi9625307 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WT164 UT WOS:A1997WT16400002 PM 9099999 ER PT J AU Bhat, MK McPhie, P Cheng, SY AF Bhat, MK McPhie, P Cheng, SY TI Critical role of glutamine 252 in the hormone-dependent transcriptional activity of the thyroid hormone beta 1 nuclear receptor SO BIOCHEMISTRY LA English DT Article ID RETINOIC ACID RECEPTORS; LIGAND-BINDING DOMAIN; CRYSTAL-STRUCTURE; RESPONSE ELEMENT; CO-REPRESSOR; DNA; ANTIBODIES; PROTEIN; ALPHA; SITE AB TO understand the molecular basis of the ligand-dependent transcriptional activity of thyroid hormone nuclear receptors (TRs), we investigated the effect of mutation of glutamine 252 (Q252) onthe function of human TR subtype beta 1 (wTR beta 1). Q252 is conserved in TRs in all species and is located in a region of the hormone binding domain that has been shown to undergo 3,3',5-triiodo-L-thyronine (T-3) induced conformational changes. Q252 was mutated to Gly (Q252G) or Asn (Q252N) and their immunoreactivity, hormone, and DNA binding activities were characterized. Mutants Q252G and Q252N bound to T-3 with similar affinity as the wTR beta 1. However, they failed to interact with a monoclonal anti-wTR beta(1) antibody whose epitope is located in the region of amino acids 248-256, suggesting that mutation of Q252 to Gly or Asn resulted in local structural alteration in TR beta 1. In addition, mutation of Glu to Gly or Asn led to increases in their binding to the thyroid hormone response elements (TREs) as homodimers and as heterodimers with the retinoid X receptor. Mutants Q252G and Q252N were more effective as repressors in the absence of T-3, while both had a 1.5-2-fold higher T-3-dependent transcriptional activity mediated by three TREs than the wTR beta 1. The increases in the transcriptional activity were not due to an increase in the expression of the mutant receptor proteins because the in vive expression level of the mutant receptor proteins was identical to that of the wTR beta 1. Our data indicate that the T-3-dependent transcriptional activity is not entirely dependent on the T-3 binding activity of the receptor. The interplay of ligand and DNA binding domains plays a pivotal role in the transcriptional activity of the TRs. C1 NIDDKD,BIOCHEM PHARMACOL LAB,NIH,BETHESDA,MD 20892. NCI,MOL BIOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 37 TC 1 Z9 1 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 8 PY 1997 VL 36 IS 14 BP 4233 EP 4239 DI 10.1021/bi962658o PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WT164 UT WOS:A1997WT16400021 PM 9100018 ER PT J AU Barouch, W Prasad, K Greene, L Eisenberg, E AF Barouch, W Prasad, K Greene, L Eisenberg, E TI Auxilin-induced interaction of the molecular chaperone Hsc70 with clathrin baskets SO BIOCHEMISTRY LA English DT Article ID HEAT-SHOCK PROTEIN; UNCOATING ATPASE; COATED VESICLES; DNAK CHAPERONE; BOVINE BRAIN; BINDING; DISSOCIATION; HYDROLYSIS; NUCLEOTIDE; HSP70 AB We previously reported that a 100-kDa cofactor, recently identified as auxilin, is a DnaT homolog which is required for Hsc70 to uncoat clathrin baskets. In the present study we investigated the effect of auxilin on the interaction of Hsc70 with pure clathrin baskets at pH 6, where no uncoating occurs. In a reaction which required auxilin, the baskets activated the Hsc70 ATPase activity more than 100-fold with an apparent dissociation constant of about 0.2 mu M. Maximal ATPase activity occurred at a 1 to 1 molar ratio of auxilin to clathrin triskelion independent of the Hsc70 concentration suggesting that auxilin is primarily complexed with the clathrin baskets. The binding of Hsc70 to baskets also required auxilin, but less auxilin was needed for maximum binding than for maximum ATPase activity showing that auxilin can catalytically induce binding of Hsc70. The binding also required ATP; Hsc70 dissociated from baskets with a 6 min half-life when ATP was hydrolyzed to ADP. In contrast to auxilin, the assembly proteins, AP-2 and AP(180), did not support activation of the Hsc70 ATPase activity by clathrin baskets nor did Soluble clathrin triskelions at pH 7 significantly activate the ATPase activity with auxilin present. Therefore, the interaction of auxilin, clathrin baskets, and Hsc70-ATP is highly specific with auxilin first binding to a clathrin triskelion in the baskets and then Hsc70-ATP strongly binding to the auxilin-clathrin complex; the auxilin can then migrate to another clathrin triskelion before the ATPase cycle is complete. C1 NHLBI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. NR 22 TC 49 Z9 52 U1 1 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 8 PY 1997 VL 36 IS 14 BP 4303 EP 4308 DI 10.1021/bi962727z PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WT164 UT WOS:A1997WT16400029 PM 9100026 ER PT J AU SchartonKersten, TM Yap, G Magram, J Sher, A AF SchartonKersten, TM Yap, G Magram, J Sher, A TI Inducible nitric oxide is essential for host control of persistent but not acute infection with the intracellular pathogen Toxoplasma gondii SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ANTI-MICROBIAL ACTIVITY; NECROSIS-FACTOR-ALPHA; MACROPHAGE OXIDATIVE-METABOLISM; INTERFERON-GAMMA; L-ARGININE; IFN-GAMMA; LISTERIA-MONOCYTOGENES; ACTIVATED MACROPHAGES; TRYPANOSOMA-CRUZI; PERITONEAL-MACROPHAGES AB The induction by IFN-gamma of reactive nitrogen intermediates has been postulated as a major mechanism of host resistance to intracellular pathogens. To formally test this hypothesis in vivo, the course of Toxoplasma gondii infection was assessed in nitric oxide synthase (iNOS) -/- mice. As expected, macrophages from these animals displayed defective microbicidal activity against the parasite in vitro. Nevertheless, in contrast to IFN-gamma-/- or IL-12 p40-/- animals, iNOS-deficient mice survived acute infection and controlled parasite growth at the site of inoculation. This early resistance was ablated by neutralization of IFN-gamma or IL-12 in vivo and markedly diminished by depletion of neutrophils, demonstrating the existence of previously unappreciated NO independent mechanisms operating against the parasite during early infection. By 3-4 wk post infection, however, iNOS knockout mice did succumb to T. gondii. At that stage parasite expansion and pathology were evident in the central nervous system but not the periphery suggesting that the protective role of nitric oxide against this intracellular infection is tissue specific rather than systemic. C1 HOFFMANN LA ROCHE INC,DEPT INFLAMMAT & AUTOIMMUNE DIS,NUTLEY,NJ 07110. RP SchartonKersten, TM (reprint author), NIAID,PARASIT DIS LAB,IMMUNOBIOL SECT,NIH,BLDG 4,RM 126,BETHESDA,MD 20892, USA. NR 68 TC 251 Z9 253 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 7 PY 1997 VL 185 IS 7 BP 1261 EP 1273 DI 10.1084/jem.185.7.1261 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA WU183 UT WOS:A1997WU18300012 PM 9104813 ER PT J AU Kerkau, T Bacik, I Bennink, JR Yewdell, JW Hunig, T Schimpl, A Schubert, U AF Kerkau, T Bacik, I Bennink, JR Yewdell, JW Hunig, T Schimpl, A Schubert, U TI The human immunodeficiency virus type 1 (HIV-1) vpu protein interferes with an early step in the biosynthesis of major histocompatibility complex (MHC) class I molecules SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ENDOPLASMIC-RETICULUM; T-CELLS; ANTIGEN PRESENTATION; CYTOPLASMIC DOMAIN; RAPID DEGRADATION; DOWN-REGULATION; INFECTED-CELLS; AIDS VIRUS; HTLV-III; EXPRESSION AB The human immunodeficiency virus type 1 (HIV-1) vpu gene encodes a small integral membrane phosphoprotein with two established functions. degradation of the viral coreceptor CD4 in the endoplasmic reticulum (ER) and augmentation of virus particle release from the plasma membrane of HIV-1-infected cells. We show here that Vpu is also largely responsible for the previously observed decrease in the expression of major histocompatibility complex (MHC) class I molecules on the surface of HIV-1-infected cells. Cells infected with HIV-1 isolates that fail to express Vpu, or that express genetically modified forms of Vpu that no longer induce CD4 degradation, exhibit little downregulation of MHC class I molecules. The effect of Vpu on class I biogenesis was analyzed in more detail using a Vpu-expressing recombinant vaccinia virus (VV), VV-expressed Vpu induces the rapid loss of newly synthesized endogenous or VV-expressed class I heavy chains in the ER, detectable either biochemically or by reduced cell surface expression. This effect is of similar rapidity and magnitude as the VV-expressed Vpu-induced degradation of CD4. Vpu had no discernible effects on cell surface expression of VV-expressed mouse CD54, demonstrating the selectivity of its effects on CD4 and class I heavy chains. VV-expressed Vpu does not detectably affect class I molecules that have been exported from the ER. The detrimental effects of Vpu on class I molecules could be distinguished from those caused by VV-expressed herpes virus protein ICP47, which acts by decreasing the supply of cytosolic peptides to class I molecules, indicating that Vpu functions in a distinct manner from 1CP47. Based on these findings, we propose that Vpu-induced downregulation of class I molecules may be an important factor in the evolutionary selection of the HIV-1-specific vpu gene by contributing to the inability of CD8(+) T cells to eradicate HIV-1 from infected individuals. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. UNIV WURZBURG,INST VIROL & IMMUNOBIOL,D-8700 WURZBURG,GERMANY. NIAID,MOL MICROBIOL LAB,BETHESDA,MD 20892. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 75 TC 134 Z9 137 U1 1 U2 6 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 APR 7 PY 1997 VL 185 IS 7 BP 1295 EP 1305 DI 10.1084/jem.185.7.1295 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA WU183 UT WOS:A1997WU18300015 PM 9104816 ER PT J AU Palmer, LD Weng, NP Levine, BL June, CH Lane, HC Hodes, RJ AF Palmer, LD Weng, NP Levine, BL June, CH Lane, HC Hodes, RJ TI Telomere length, telomerase activity, and replicative potential in HIV infection: Analysis of CD4(+) and CD8(+) T cells from HIV-discordant monozygotic twins SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HUMAN FIBROBLASTS; LYMPHOCYTES; AGE AB To address the possible role of replicative senescence in human immunodeficiency virus (HIV) infection, telomere length, telomerase activity, and in vitro replicative capacity were assessed in peripheral blood T cells from HIV+ and HIV- donors. Genetic and age-specific effects on these parameters were controlled by studying HIV-discordant pairs of monozygotic twins. Telomere terminal restriction fragment (TRF) lengths from CD4(+) T cells of HIV+ donors were significantly greater than those from HIV- twins. In contrast, telomere lengths in CD8(+) T cells from HIV+ donors were shorter than in HIV- donors. The in vitro replicative capacity of CD4(+) cells from HIV+ donors was equivalent to that of HIV- donors in response to stimulation through T cell receptor CD3 and CD28. Little or no telomerase activity was detected in freshly isolated CD4(+) or CD8(+) lymphocytes from HIV+ or HIV- donors, but was induced by in vitro stimulation of both HIV+ and HIV- donor cells. These results suggest that HIV infection is associated with alterations in the population dynamics of both CD4(+) and CD8(+) T cells, but fail to provide evidence for clonal exhaustion or replicative senescence as a mechanism underlying the decline in CD4(+) T cells of HIV-infected donors. C1 NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20889. NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. NIA,NIH,BETHESDA,MD 20892. RI Levine, Bruce/D-1688-2009 NR 20 TC 106 Z9 108 U1 0 U2 4 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 APR 7 PY 1997 VL 185 IS 7 BP 1381 EP 1386 DI 10.1084/jem.185.7.1381 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA WU183 UT WOS:A1997WU18300023 PM 9104824 ER PT J AU Ezzitouni, A Marquez, VE AF Ezzitouni, A Marquez, VE TI Conformationally locked carbocyclic nucleosides built on a bicyclo[3.1.0]hexane template with a fixed Southern conformation. Synthesis and antiviral activity SO JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1 LA English DT Article ID THYMIDINE; DERIVATIVES AB The construction of carbocyclic nucleosides with a fixed E-3 ring pucker in the Southern hemisphere of the pseudorotational cycle is achieved from a common precursor carbocyclic amine, (1S,3S,4R,5S)-3-benzyloxy-4-benzyloxymethyl- 1-aminobicyclo[3.1,0]hexane 20. This carbocyclic amine is efficiently assembled from optically pure 2-benzyloxymethylcyclopent-3-enol 11 in ten steps. The key cyclopropanation step is performed on (3R,4S)-1-cyano-4-benzyloxy-3-(benzyloxymethyl)cyclopentane 15, and proceeds regio- and stereo-selectively to give the critical cyanocarbocyclic intermediate 17 from which the amine 20 is subsequently obtained. Synthesis of the pyrimidine analogues 6-8 is accomplished via the intermediate acyclic acryloylureas 21 and 22. Preparation of purines 9 and 10 required prior N-formylation of the corresponding 4,6-dichioro-5-aminopyrimidine and 4,6-dichloro-2,5-diaminopyrimidine heterocyclic precursors for efficient coupling with amine 20. Except for (S)-2'-deoxy-methanocarba-A (9, the 2'-deoxyadenosine analogue), all Southern conformers appear to be devoid of antiviral activity. C1 NCI,MED CHEM LAB,DIV BASIC SCI,NATL INST HLTH,BETHESDA,MD 20892. NR 14 TC 64 Z9 64 U1 0 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON ROAD, CAMBRIDGE, CAMBS, ENGLAND CB4 4WF SN 0300-922X J9 J CHEM SOC PERK T 1 JI J. Chem. Soc.-Perkin Trans. 1 PD APR 7 PY 1997 IS 7 BP 1073 EP 1078 DI 10.1039/a604352f PG 6 WC Chemistry, Organic SC Chemistry GA WU664 UT WOS:A1997WU66400017 ER PT J AU Chang, HT Chen, N Sullivan, JV Chrambach, A AF Chang, HT Chen, N Sullivan, JV Chrambach, A TI Preparative electrophoresis in a concentrated polymer solution: Automated procedure for microsome isolation SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID SDS-PROTEIN; APPARATUS; SEPARATION; RECOVERY AB A recently introduced automated gel electrophoresis apparatus with an intermittent scanning of the migration path, the HPGE 1000 apparatus (LabIntelligence, Belmont, CA) has a unique preparative feature: A recovery cup can be automatically positioned on the band of interest, which is then electroeluted with fluorescence monitoring of recovery. Electroelution time is extended stepwise until quantitative recovery is attained. This preparative procedure has been extended fi-om electrophoresis in gels to that of subcellular-sized particles in concentrated polymer solutions (Chang ct al., Electrophoresis 17, 776-780, 1996). However, that application required manual rather than computer-directed positioning of the recovery chamber over the band. The present report details a modification of instrumentation and procedure by which automated operation was restored. The modified procedure extends the benefits of automation and known quantitative recovery to isolation of particles too large to enter into gels. (C) 1997 Academic Press. C1 NICHHD,MACROMOL ANAL SECT,LAB CELLULAR & MOL BIOPHYS,BETHESDA,MD 20892. NIH,MECH INSTRUMENTAT FABRICAT SECT,BIOCHEM ENGN & INSTRUMENTAT PROGRAM,NATL CTR RES RESOURCES,BETHESDA,MD 20892. RP Chang, HT (reprint author), NATL TAIWAN UNIV,DEPT CHEM,TAIPEI 10764,TAIWAN. RI Chang, Huan-Tsung/C-1183-2011; OI Chang, Huan-Tsung/0000-0002-5393-1410 NR 10 TC 6 Z9 6 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD APR 5 PY 1997 VL 247 IS 1 BP 111 EP 114 DI 10.1006/abio.1997.2048 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WT591 UT WOS:A1997WT59100017 PM 9126379 ER PT J AU Saroff, HA Kiefer, JE AF Saroff, HA Kiefer, JE TI Analysis of the binding of ligands to large numbers of sites: The binding of tryptophan to the 11 sites of the trp RNA-binding attenuation protein SO ANALYTICAL BIOCHEMISTRY LA English DT Article AB Analysis of the cooperative binding of ligands may provide insight into the underlying mechanisms of biological control. Binding of L-tryptophan at each juncture in the ring of 11 subunits of the trp RNA-binding attenuation protein exhibits cooperativity. To analyze binding of this kind we have developed both the matrix and combinatorial procedures for binding to large numbers of sites. A new, exact, and fast combinatorial procedure is presented. In this procedure the sites may be single or overlapping in a linear lattice or in the form of a ring. The dimensions of the ring of 11 binding sites for L-tryptophan on the trp RNA-binding attenuation protein are such as to prevent direct interactions between the L-tryptophan molecules. Reasonable and explicit assumptions on analyzing the binding data lead to the conclusion that binding of L-tryptophan raises the energy level of (destabilizes) the 11 membered structure. (C) 1997 Academic Press. C1 NIDDKD,DIV COMP RES & TECHNOL,PHYS SCI LAB,NIH,BETHESDA,MD 20892. RP Saroff, HA (reprint author), NIDDKD,BIOCHEM PHARMACOL LAB,NIH,BETHESDA,MD 20892, USA. NR 15 TC 4 Z9 4 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD APR 5 PY 1997 VL 247 IS 1 BP 138 EP 142 DI 10.1006/abio.1997.2039 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA WT591 UT WOS:A1997WT59100021 PM 9126383 ER PT J AU Yim, HS Kang, JH Chock, PB Stadtman, ER Yim, MB AF Yim, HS Kang, JH Chock, PB Stadtman, ER Yim, MB TI A familial amyotrophic lateral sclerosis-associated A4V Cu,Zn-Superoxide dismutase mutant has a lower K-m for hydrogen peroxide SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CU,ZN SUPEROXIDE-DISMUTASE; TRANSGENIC MICE; MUTATIONS; GENE; SUPEROXIDE-DISMUTASE-1; COPPER; CELLS AB Point mutations of Cu,Zn-superoxide dismutase (Cu,Zn-SOD) have been linked to familial amyotrophic lateral sclerosis (FALS). We reported that Cu,Zn-SOD can catalyze free radical generation and a FALS mutant, G93A, exhibits an enhanced free radical-generating activity, while its dismutation activity is identical to that of the wild-type enzyme (Yim, M. B., Bang J.-H., Yim, H.-S., Kwak, H.-S., Chock, P. B., and Stadtman, E. R. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 5709-5714). The A4V mutation is both the most commonly detected of FALS-associated SOD1 mutations and among the most clinically severe (Rosen, D. R., Bowling, A. C., Patterson, D., Usdin, T. B., Sapp, P., Mezey, E., McKenna-Yasek, D., O'Regan, J. P., Rahmani, Z., Ferrante, R. J., Brownstein, M. J., Kowall, N. W., Beal, M. F., Horvitz, H. R., and Brown, R. H., Jr. (1994) Rum. Mol. Genet. 3, 981-987). We cloned the cDNA for the FALS A4V mutant, overexpressed the protein in Sf9 insect cells, purified the protein, and studied its enzymic activities. Our results show that the mutant and wild-type enzymes contain one copper ion per subunit and have identical dismutation activities. However, the free radical-generating activity of the mutant, as measured by the spin trapping method at low H2O2 concentration, is enhanced relative to that of the wild-type and G93A enzyme (wild-type < G93A < A4V). This is due to the decrease in the K-m value for H2O2, wild-type > G93A > A4V, while the k(cat) is identical for these enzymes. Thus, the FALS symptoms are not associated with the reduction in the dismutation activity of the mutant enzyme. The fact that the A4V mutant has the lowest K-m for H2O2 is correlated to the clinical severity observed with the A4V patients, if FALS is associated with a differential gain of the free radical-generating function of the Cu,Zn-SOD mutant. C1 NHLBI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. NR 22 TC 143 Z9 144 U1 0 U2 8 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 APR 4 PY 1997 VL 272 IS 14 BP 8861 EP 8863 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WU037 UT WOS:A1997WU03700007 PM 9083002 ER PT J AU BirchenallRoberts, MC Yoo, YD Bertolette, DC Lee, KH Turley, JM Bang, OS Ruscetti, FW Kim, SJ AF BirchenallRoberts, MC Yoo, YD Bertolette, DC Lee, KH Turley, JM Bang, OS Ruscetti, FW Kim, SJ TI The p120-v-Abl protein interacts with E2F-1 and regulates E2F-1 transcriptional activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ABL TYROSINE KINASE; RETINOBLASTOMA GENE-PRODUCT; HUMAN MYC PROMOTER; LARGE T-ANTIGEN; S-PHASE ENTRY; V-ABL; CELL-CYCLE; C-ABL; NEOPLASTIC TRANSFORMATION; TRANS-ACTIVATION AB The E2F family of transcription factors regulates cell cycle progression, and deregulated expression of E2F-1 can lead to neoplastic transformation. In myeloid cells, introduction and expression of the Abelson leukemia virus causes growth factor independence. Here, the p120 v-Abl protein activates E2F-1-mediated transcription through a physical interaction with the E2F-1 transcription factor. BCR-Abl and c-Abl also stimulate ESF-1-mediated transcription. Our results suggest a new mechanism by which v-Abl leads to factor-independent myeloid cell proliferation: the activation of E2F-1-mediated transcription. C1 NCI,CHEMOPREVENT LAB,DIV BASIC SCI,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,LAB LEUKOCYTE BIOL,DIV BASIC SCI,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,INTRAMURAL RES SUPPORT PROGRAM,SAIC FREDERICK,FREDERICK,MD 21702. NR 62 TC 12 Z9 12 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 APR 4 PY 1997 VL 272 IS 14 BP 8905 EP 8911 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WU037 UT WOS:A1997WU03700015 PM 9083010 ER PT J AU Kim, HJ Okazaki, IJ Takada, T Moss, J AF Kim, HJ Okazaki, IJ Takada, T Moss, J TI An 18-kDa domain of a glycosylphosphatidylinositol-linked NAD:Arginine ADP-ribosyltransferase possesses NAD glycohydrolase activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SKELETAL-MUSCLE CELLS; DIPHTHERIA-TOXIN; PERTUSSIS TOXIN; PSEUDOMONAS-AERUGINOSA; ESCHERICHIA-COLI; ASPARTIC-ACID; EXOTOXIN-A; TRANSFERASE; PROTEINS; SUBUNIT AB Transfection of NMU (rat mammary adenocarcinoma) cells with NAD:arginine ADP-ribosyltransferase cDNAs from Yac-1 murine lymphoma cells or rabbit muscle increased NAD glycohydrolase and ADP-ribosyltransferase activities. The ADP-ribosyltransferase activity was released from transformed NMU cells by phosphatidylinositol-specific phospholipase C (PI-PLC) and hence glycosylphosphatidylinositol (GPI)-anchored, whereas the NAD glycohydrolase (NADase) activity remained cell-associated. By gel permeation chromatography, the size of the PI-PLC-released transferase was similar to 40 kDa and that of the detergent-solubilized NADase was similar to 100 kDa. Using polyclonal antibodies against rabbit muscle transferase on Western blots, similar to 18- and similar to 30-kDa band were visualized among proteins from the NADase fractions and 38-40-kDa bands with protein from the transferase fractions. Incubation of blots with [P-32]NAD led to the incorporation of radioactivity into the immunoreactive transferase bands of 38 kDa and the immunoreactive NADase band of similar to 18 kDa. These data suggest that proteolysis of ADP-ribosyltransferase synthesized in transformed NMU cells might result in the formation of aggregates of an 18-kDa NAD glycohydrolase. A fusion protein with glutathione S-transferase linked to the amino terminus of Yac-1 transferase, from which the amino-terminal 121 amino acids had been deleted (GST-Yac-1-delta 121), exhibited NADase, but not transferase, activity. The size of the recombinant fusion protein was similar to that of the proteolytic fragment seen in NMU cells transformed with transferase cDNA. These results are compatible with the conclusion that the NAD glycohydrolase activity was generated in NMU cells by proteolysis of ADP-ribosyltransferase, with release of a carboxyl-terminal fragment that possesses glycohydrolase but not transferase activity, i.e. the carboxyl-terminal portion of the transferase can exist as a catalytically active NADase. RP Kim, HJ (reprint author), NHLBI,PULM CRIT CARE MED BRANCH,NIH,10 CTR DR,MSC 1434,BLDG 10,RM 5N-307,BETHESDA,MD 20892, USA. NR 39 TC 6 Z9 6 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 APR 4 PY 1997 VL 272 IS 14 BP 8918 EP 8923 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WU037 UT WOS:A1997WU03700017 PM 9083012 ER PT J AU Zhu, XG McPhie, P Lin, KH Cheng, SY AF Zhu, XG McPhie, P Lin, KH Cheng, SY TI The differential hormone-dependent transcriptional activation of thyroid hormone receptor isoforms is mediated by interplay of their domains SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RETINOID-X RECEPTOR; NUCLEAR RECEPTOR; BINDING-CAPACITY; CO-REPRESSOR; DNA; PROTEIN; CELLS; GENE; DIMERIZATION; SEQUENCE AB Human thyroid hormone nuclear receptor isoforms (TR alpha 1 and TR beta 1) express differentially in a tissue-specific and development-dependent manner. It is unclear whether these two isoforms have differential functions. We analyzed their interaction with a thyroid hormone response element with half-site binding motifs arranged in an everted repeat separated by six nucleotides (F2). Despite extensive sequence homologies, the two isoforms bound to F2 with different affinities and ratios of homodimer/monomer. Using F2-containing reporter gene, we found that the transcriptional activity of TR beta 1 was similar to 6-fold higher than that of TR alpha 1. The lower activity of TR alpha 1 was not due to differences in expression of the two isoforms because similar nuclear localization patterns were observed. To understand the structural determinants responsible for these differences, we constructed chimeric receptors in which hinge regions (domain D), hormone binding domains (domain E), and domains (D + E) were sequentially interchanged and their activities were compared. Chimeric TRs containing the domains D, E or (D + E) of TR beta 1 showed increased propensities to form homodimers and mediated higher transactivation activities than TR alpha 1. Thus, differential transactivation activities of TR isoforms are mediated by interplay of their domains and could serve as an important regulatory mechanism to achieve diversity and specificity of pleiotropic T-3 effect. C1 NIDDKD,MOL BIOL LAB,DIV BASIC SCI,NATL INST HLTH,BETHESDA,MD 20892. NIDDKD,BIOCHEM PHARMACOL LAB,NATL INST HLTH,BETHESDA,MD 20892. CHANG GUANG MED COLL,DEPT BIOCHEM,TAYUAN,TAIWAN. NR 35 TC 29 Z9 30 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 APR 4 PY 1997 VL 272 IS 14 BP 9048 EP 9054 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WU037 UT WOS:A1997WU03700035 PM 9083030 ER PT J AU Sathyamoorthy, M deMendez, I Adams, AG Leto, TL AF Sathyamoorthy, M deMendez, I Adams, AG Leto, TL TI p40(phox) down-regulates NADPH oxidase activity through interactions with its SH3 domain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-FREE SYSTEM; CYTOSOLIC COMPONENT; ACTIVATION; COMPLEX; P67(PHOX); P47(PHOX); PROTEINS; P67-PHOX; RECONSTITUTION; P47-PHOX AB The NADPH oxidase of phagocytes generates microbicidal oxidants in response to a variety of stimuli. Its activation and assembly involve multiple SH3 domain interactions among several oxidase components. Here we present evidence that the cytosolic oxidase-associated protein, p40(phox), mediates down-regulation of NADPH oxidase through interactions with its SH3 domain, Recombinant p40(phox) was produced in several eukaryotic expression systems (insect, mammalian, and yeast) to explore its role in oxidase function in relation to domains involved in interactions with other factors, p47(phox) and p67(phox). p40(phox) inhibited oxidase activity in vitro when added to neutrophil membranes and recombinant p47(phox), P67(phox) and p21rac. Co-transfection of p40(phox) into R562 cells resulted in significant decreases (similar to 40%) in whole cell oxidase activity. Furthermore, the isolated SH3 domain of p40(phox) was even more effective in inhibiting whole cell oxidase activity, consistent with experiments showing that this domain binds to the same proline-rich target in p47(phox) (residues 358-390) that interacts with p67(phox). In contrast, deletion of the carboxyl-terminal domain of p40(phox) that binds to p67(phox) did not relieve its oxidase inhibitory effects, Thus, p40(phox) appears to down-regulate oxidase function by competing with an SH3 domain interaction between other essential oxidase components. C1 NIAID,HOST DEF LAB,NATL INST HLTH,BETHESDA,MD 20892. NR 35 TC 92 Z9 94 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 APR 4 PY 1997 VL 272 IS 14 BP 9141 EP 9146 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WU037 UT WOS:A1997WU03700048 PM 9083043 ER PT J AU Marshall, AD Darbyshire, JF Hunter, AP McPhie, P Jakoby, WB AF Marshall, AD Darbyshire, JF Hunter, AP McPhie, P Jakoby, WB TI Control of activity through oxidative modification at the conserved residue Cys(66) of aryl sulfotransferase IV SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE-ESTER SULFOTRANSFERASE; S-THIOLATION; PHENOL SULFOTRANSFERASE; RESPIRATORY BURST; RAT-LIVER; GLUTATHIONE; DISULFIDE; PROTEINS; IDENTIFICATION; STIMULATION AB Oxidation at Cys(66) of rat liver aryl sulfotransferase IV alters the enzyme's catalytic activity, pH optima and substrate specificity. Although this is a cytosolic detoxication enzyme, the pH optimum for the standard assay substrate 4-nitrophenol is at pH 5.5; upon oxidation, the optimum changes to the physiological pH range. The principal effect of the change in pH optimum is activation, which is manifest by an increase in K'(cat) without any major influence on substrate binding. In contrast, with tyrosine methyl ester as a substrate, the enzyme's optimum activity occurs at pH 8.0; upon oxidation, it ceases to be a substrate at any pH. The presence of Cys(66) was essential for activation to occur, thereby providing a putative reason underlying the conserved nature of this cysteine throughout the phenol sulfotransferase family. Mapping of disulfides by mass spectrometry showed the critical event to be the oxidation of Cys(66) to form a disulfide with either Cys(232) or glutathione, either one is effective. These results point to a mechanism for regulating the activity of a key enzyme in xenobiotic detoxication during cellular oxidative stress. C1 NIDDK,SECT ENZYMES,BIOCHEM & METAB LAB,NATL INST HLTH,BETHESDA,MD 20892. UNIV WASHINGTON,SCH PHARM,DEPT MED CHEM,SEATTLE,WA 98195. NR 28 TC 32 Z9 33 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 4 PY 1997 VL 272 IS 14 BP 9153 EP 9160 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WU037 UT WOS:A1997WU03700050 PM 9139043 ER PT J AU Uchiumi, T Longo, DL Ferris, DK AF Uchiumi, T Longo, DL Ferris, DK TI Cell cycle regulation of the human polo-like kinase (PLK) promoter SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CCAAT-BINDING-FACTOR; PROTEIN-KINASE; TRANSCRIPTIONAL REPRESSION; CDC25C TRANSCRIPTION; DROSOPHILA POLO; NF-Y; GENE; EXPRESSION; SPINDLE; IDENTIFICATION AB Plk (polo-like kinase) is a serine-threonine kinase that appears to function in mitotic control in mammalian cells. We demonstrated previously that PLK mRNA expression is low at the G(1)-S transition, increases during S phase, and is maximally expressed during G(2)-M. In the present study, we have cloned the human PLK gene and analyzed the structure and function of 2 kilobases of its 5'-flanking region. Using synchronized cultures of HeLa cells transfected with PLK promoter/luciferase constructs, we show that the promoter of PLK is activated at S phase and is maximal at G(2)-M phase. Using various PLK promoter/luciferase constructs, we show that three activating regions are located between 35 and 93 base pairs upstream of the transcription initiation site. We identified a repressor element (CDE/CHR) in the region of the transcription start site, and mutations within this element diminished cell cycle regulation of transcription. C1 NCI,INTRAMURAL RES SUPPORT PROGRAM,SCI APPLICAT INT CORP,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NCI,LAB LEUKOCYTE BIOL,DIV CANC TREATMENT,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NIA,BALTIMORE,MD 21224. NR 28 TC 104 Z9 108 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 4 PY 1997 VL 272 IS 14 BP 9166 EP 9174 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WU037 UT WOS:A1997WU03700052 PM 9083047 ER PT J AU Lin, SJ Pufahl, RA Dancis, A OHalloran, TV Culotta, VC AF Lin, SJ Pufahl, RA Dancis, A OHalloran, TV Culotta, VC TI A role for the Saccharomyces cerevisiae ATX1 gene in copper trafficking and iron transport SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID WILSON-DISEASE GENE; SUPEROXIDE-DISMUTASE; CANDIDATE GENE; MERCURY-RESISTANCE; MENKES DISEASE; FET3 GENE; YEAST; PROTEIN; ENCODES; MUTANTS AB The ATX1 gene of Saccharomyces cerevisiae was originally identified as a multi-copy suppressor of oxidative damage in yeast lacking superoxide dismutase. We now provide evidence that Atx1p helps deliver copper to the copper requiring oxidase Fet3p involved in iron uptake. atx1 Delta null mutants are iron-deficient and are defective in the high affinity uptake of iron. These defects due to ATX1 inactivation are rescued by copper treatment, and the same has been reported for strains lacking either the cell surface copper transporter, Ctr1p, or the putative copper transporter in the secretory pathway, Ccc2p. Atx1p localizes to the cytosol, and our studies indicate that it functions as a carrier for copper that delivers the metal from the cell surface Ctr1p to Ccc2p and then to Fet3p within the secretory pathway. The iron deficiency of atx1 mutants is augmented by mutations in END3 blocking endocytosis, suggesting that a parallel pathway for intracellular copper trafficking is mediated by endocytosis. As additional evidence for the role of Atx1p in iron metabolism, we find that the gene is induced by the same iron-sensing trans-activator, Aft1p, that regulates CCC2 and FET3. C1 JOHNS HOPKINS UNIV, SCH PUBL HLTH, DEPT ENVIRONM HLTH SCI, DIV TOXICOL SCI, BALTIMORE, MD 21205 USA. NICHHD, CELL BIOL & METAB BRANCH, NIH, BETHESDA, MD 20892 USA. NORTHWESTERN UNIV, DEPT CHEM, EVANSTON, IL 60208 USA. FU NIGMS NIH HHS [GM 38784, R01 GM054111]; PHS HHS [R01 5016] NR 44 TC 296 Z9 307 U1 0 U2 9 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 APR 4 PY 1997 VL 272 IS 14 BP 9215 EP 9220 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WU037 UT WOS:A1997WU03700059 PM 9083054 ER PT J AU Klomp, LWJ Lin, SJ Yuan, DS Klausner, RD Culotta, VC Gitlin, JD AF Klomp, LWJ Lin, SJ Yuan, DS Klausner, RD Culotta, VC Gitlin, JD TI Identification and functional expression of HAH1, a novel human gene involved in copper homeostasis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID WILSON-DISEASE GENE; SACCHAROMYCES-CEREVISIAE ENCODES; CANDIDATE GENE; MENKES DISEASE; MOLECULAR CHARACTERIZATION; TRANSPORTING ATPASE; CERULOPLASMIN GENE; RAT CERULOPLASMIN; METALLOTHIONEIN-I; IRON UPTAKE AB To search for a mammalian homologue of ATX1, a human liver cDNA library was screened and a cDNA clone was isolated, which encodes a protein with 47% amino acid identity to Atx1p including conservation of the MTCXGC copper-binding domain. RNA blot analysis using this cDNA identified an abundant 0.5-kilobase mRNA in all human tissues and cell lines examined. Southern blot analysis using this same clone indicated that the corresponding gene exists as a single copy in the haploid genome, and chromosomal localization by fluorescence in situ hybridization detected this locus at the interface between bands 5q32 and 5q33. Yeast strains lacking copper/zinc superoxide dismutase (SOD1) are sensitive to redox cycling agents and dioxygen and are auxotrophic for lysine when grown in air, and expression of this human ATX1 homologue (HAH1) in these strains restored growth on lysine-deficient media, Yeast strains lacking ATX1 are deficient in high affinity iron uptake and expression of HAH1 in these strains permits growth on iron-depleted media and results in restoration of copper incorporation into newly synthesized Fet3p. These results identify HAH1 as a novel ubiquitously expressed protein, which may play an essential role in antioxidant defense and copper homeostasis in humans. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT ENVIRONM HLTH SCI,DIV TOXICOL SCI,BALTIMORE,MD 21205. NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892. WASHINGTON UNIV,SCH MED,EDWARD MALLINCKRODT DEPT PEDIAT,ST LOUIS,MO 63110. FU NIDDK NIH HHS [DK44464]; NIGMS NIH HHS [GM50016] NR 40 TC 280 Z9 283 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 4 PY 1997 VL 272 IS 14 BP 9221 EP 9226 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WU037 UT WOS:A1997WU03700060 PM 9083055 ER PT J AU Webster, JC Jewell, CM Bodwell, JE Munck, A Sar, M Cidlowski, JA AF Webster, JC Jewell, CM Bodwell, JE Munck, A Sar, M Cidlowski, JA TI Mouse glucocorticoid receptor phosphorylation status influences multiple functions of the receptor protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DOWN-REGULATION; ANTIPEPTIDE ANTIBODIES; THYROID-HORMONE; GENE-EXPRESSION; NUCLEAR; ACTIVATION; CELLS; TRANSCRIPTION; SUPERFAMILY; SITES AB Although studies have shown that the mouse glucocorticoid receptor (mGR) contains eight phosphorylation sites (Bodwell, J. E., Orti, E., Coull, J. M., Pappin, D. J. C., Smith, L. I., and Swift, F. (1991) J. Biol. Chem. 266, 7549-7555), the effect of phosphorylation on receptor function is unclear, We have examined the consequences of single or multiple phosphorylation site mutations on several properties of mGR including receptor expression, ligand-dependent nuclear translocation, hormone-mediated transactivation, ligand-dependent down-regulation of mGR, and receptor protein half-life. Mutations had little effect on receptor expression, subcellular distribution, ligand-dependent nuclear translocation, or on the ability to activate hormone-mediated transcription from a complex (murine mammary tumor virus) promoter. In contrast, the phosphorylation status of the mGR had a profound effect on the ability to transactivate a minimal promoter containing simple glucocorticoid response elements after hormone administration. Similarly, ligand-dependent down-regulation by glucocorticoids of both receptor mRNA and protein was abrogated in mutants containing three or more phosphorylation site alterations. Finally, we show that the phosphorylation status of mGR has a profound effect on the stability of the glucocorticoid receptor protein, Receptors containing seven or eight mutated sites have a markedly extended half-life and do not show the ligand-dependent destabilization seen with wild type receptor, These data show that receptor phosphorylation may play a crucial role in regulating receptor levels and hence control receptor functions. C1 NIEHS,LAB SIGNAL TRANSDUCT,MOL ENDOCRINOL GRP,NIH,RES TRIANGLE PK,NC 27709. DARTMOUTH COLL,SCH MED,DEPT PHYSIOL,LEBANON,NH 03756. FU NIDDK NIH HHS [DK 03535, DK 45337, DK 47329] NR 37 TC 183 Z9 191 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 APR 4 PY 1997 VL 272 IS 14 BP 9287 EP 9293 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WU037 UT WOS:A1997WU03700069 PM 9083064 ER PT J AU Lubas, WA Frank, DW Krause, M Hanover, JA AF Lubas, WA Frank, DW Krause, M Hanover, JA TI O-linked GlcNAc transferase is a conserved nucleocytoplasmic protein containing tetratricopeptide repeats SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEAR-PORE COMPLEX; TERMINAL N-ACETYLGLUCOSAMINE; GLYCOGEN-SYNTHASE; HEXOSAMINE BIOSYNTHESIS; INSULIN-RESISTANCE; GLYCOSYLATION; PHOSPHORYLATION; GLYCOPROTEINS; GLUCOSAMINE; TRANSCRIPTION AB O-Linked GlcNAc addition and phosphorylation may compete for sites on nuclear pore proteins and transcription factors. We sequenced O-linked GlcNAc transferase from rabbit blood and identified the homologous Caenorhabditis elegans transferase gene on chromosome III. We then isolated C. elegans and human cDNAs encoding the transferase. The enzymes from the two species appear to be highly conserved; both contain multiple tetratricopeptide repeats and nuclear localization sequences, The C. elegans transferase accumulated in the nucleus and in perinuclear aggregates in overexpressing transgenic lines, O-Linked GlcNAc transferase activity was also elevated in HeLa cells transfected with the human cDNA. At least four human transcripts were observed in the tissues examined ranging in size from 4.4 to 9.3 kilobase pairs, The two largest transcripts (7.9 and 9.3 kilobase pairs) were enriched at least 12-fold in the pancreas, Based on its substrate specificity and molecular features, we propose that O-linked GlcNAc transferase is part of a glucose-responsive pathway previously implicated in the pathogenesis of diabetes mellitus. C1 NIDDK,LAB CELL BIOCHEM & BIOL,NIH,BETHESDA,MD 20892. OI Krause, Michael/0000-0001-6127-3940 NR 34 TC 304 Z9 312 U1 4 U2 13 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 APR 4 PY 1997 VL 272 IS 14 BP 9316 EP 9324 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WU037 UT WOS:A1997WU03700073 PM 9083068 ER PT J AU Bernstein, J Sella, O Le, SY ElroyStein, O AF Bernstein, J Sella, O Le, SY ElroyStein, O TI PDGF2/c-sis mRNA leader contains a differentiation-linked internal ribosomal entry site (D-IRES) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID 5' NONTRANSLATED REGION; MESSENGER-RNA; NONCODING REGION; TRANSLATION; INITIATION; ELEMENTS; EFFICIENCY; SEQUENCES AB It has become clear that a given cell type can qualitatively and quantitatively affect the expression of the platelet-derived growth factor B (PDGF2/c-sis) gene at multiple levels. In a previous report, we showed that PDGF2/c-sis 5'-untranslated region has a translational modulating activity during megakaryocytic differentiation of K562 cells. This study points to the mechanism used for this translational modulation. The unusual mRNA leader, which imposes a major barrier to conventional ribosomal scanning, was found to contain an internal ribosomal entry site that becomes more potent in differentiating cells and was termed differentiation-linked internal ribosomal entry site (D-IRES), The D-IRES element defines a functional role for the cumbersome 1022-nucleotide-long mRNA leader and accounts for its uncommon, evolutionary conserved architecture. The differentiation-linked enhancement of internal translation, which provides an additional step to the fine tuning of PDGF2/c-sis gene expression, might be employed by numerous critical regulatory genes with unusual mRNA leaders and might have widespread implications for cellular growth and development. C1 TEL AVIV UNIV,GEORGE S WISE FAC LIFE SCI,DEPT CELL RES & IMMUNOL,IL-69978 TEL AVIV,ISRAEL. NCI,MATH BIOL LAB,DCBDC,NIH,FREDERICK,MD 21702. NR 32 TC 144 Z9 144 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 APR 4 PY 1997 VL 272 IS 14 BP 9356 EP 9362 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WU037 UT WOS:A1997WU03700077 PM 9083072 ER PT J AU Brasaemle, DL Barber, T Kimmel, AR Londos, C AF Brasaemle, DL Barber, T Kimmel, AR Londos, C TI Post-translational regulation of perilipin expression - Stabilization by stored intracellular neutral lipids SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HORMONE-SENSITIVE LIPASE; LEYDIG TUMOR-CELLS; HEP G2 CELLS; APOLIPOPROTEIN-B; FATTY-ACIDS; ADIPOCYTES; STEROIDOGENESIS; LIPOPROTEINS; DROPLETS; PROTEIN AB The perilipins are a family of polyphosphorylated proteins found exclusively surrounding neutral lipid storage droplets in adipocytes and steroidogenic cells, In steroidogenic cells, the cholesterol ester-rich lipid storage droplets are encoated with perilipins A and C. This study describes the dependence of perilipin levels on neutral lipid storage in cultured Y-1 adrenal cortical cells, The addition of fatty acids and cholesterol to the culture medium of Y-1 adrenal cortical cells greatly increased the storage of cholesterol esters and triacylglycerols concomitant with the formation of many new lipid storage droplets, The addition of fatty acids to the culture medium also produced a transient 6-fold increase in levels of perilipin A, but not C, mRNA, while much larger and stable increases in both perilipin A and C proteins were observed, The increases in perilipin protein levels were dependent upon the metabolism of fatty acids to triacylglycerol or cholesterol esters, since the incubation of cells with bromopalmitate, a poorly metabolized fatty acid, failed to yield large increases in lipid content or perilipin levels, Constitutive expression of epitope-tagged perilipins in transfected Y-1 adrenal cortical cells was regulated by lipid similarly to expression of the endogenous perilipins despite an absence of untranslated perilipin mRNA sequences in the expression constructs. Epitope-tagged perilipin A mRNAs were efficiently loaded with polyribosomes whether or not fatty acids were added to the culture medium; therefore, the increase in perilipin levels in the presence of fatty acids is likely due to factors other than increased translational efficiency, We suggest that the large increase in cellular perilipin levels upon lipid loading of cells is the result of post-translational stabilization of newly synthesized perilipins by stored neutral lipids. C1 NIDDK,MEMBRANE REGULAT SECT,CELLULAR & DEV BIOL LAB,NATL INST HLTH,BETHESDA,MD 20892. NIDDK,LAB CELL BIOCH & BIOL,NATL INST HLTH,BETHESDA,MD 20892. OI Brasaemle, Dawn/0000-0002-8553-8285 NR 30 TC 101 Z9 105 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 4 PY 1997 VL 272 IS 14 BP 9378 EP 9387 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WU037 UT WOS:A1997WU03700080 PM 9083075 ER PT J AU Sakata, H Stahl, SJ Taylor, WG Rosenberg, JM Sakaguchi, R Wingfield, PT Rubin, JS AF Sakata, H Stahl, SJ Taylor, WG Rosenberg, JM Sakaguchi, R Wingfield, PT Rubin, JS TI Heparin binding and oligomerization of hepatocyte growth factor scatter factor isoforms - Heparan sulfate glycosaminoglycan requirement for Met binding and signalling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HIGH-AFFINITY RECEPTOR; FIBROBLAST GROWTH; PROTOONCOGENE PRODUCT; BIOLOGICAL-ACTIVITY; MITOGENIC ACTIVITY; RAT HEPATOCYTES; MESSENGER-RNA; IDENTIFICATION; EXPRESSION; PROTEIN AB Hepatocyte growth factor/scatter factor (HGF/SF) is a heparin-binding polypeptide that stimulates cell proliferation, motility, and morphogenesis by activation of its receptor, the c-Met tyrosine kinase. HGF/SF consists of a series of structural units, including an amino-terminal segment with a hairpin loop, four kringle domains, and a serine protease-like region. In this study, we demonstrate that the amino-terminal (N) domain retains the heparin-binding properties of full-length HGF/SF. In contrast to a previous hypothesis, selected basic amino acid residues in the hairpin loop are not critical for heparin binding, although alanine substitution at a subset of these sites markedly reduced the biological activity of the HGF/SF isoform, HGF/NK1. Covalent cross-linking experiments performed with wild-type and heparan sulfate glycosaminoglycan (HSGAG)-deficient Chinese hamster ovary (CHO) cells revealed that Met-HGF/NK1 binding was strongly dependent on HSGAG. Addition of heparin to HSGAG-deficient CHO cells not only restored ligand binding, but also increased ligand-dependent Met tyrosine phosphorylation and c-fos expression, Moreover, our results showed that heparin stimulated ligand oligomerization through an interaction with the N domain, These findings establish the importance of the N domain for heparin-ligand and ligand-ligand interactions, and demonstrate a crucial role for HSGAG in receptor binding and signal transduction. C1 NCI,CELLULAR & MOL BIOL LAB,DBS,BETHESDA,MD 20892. NIAMSD,PROT EXPRESS LAB,BETHESDA,MD 20892. NIDR,GLYCOBIOL PROGRAM,NATL INST HLTH,BETHESDA,MD 20892. NR 57 TC 104 Z9 104 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 4 PY 1997 VL 272 IS 14 BP 9457 EP 9463 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WU037 UT WOS:A1997WU03700090 PM 9083085 ER PT J AU Weitzmann, MN Woodford, KJ Usdin, K AF Weitzmann, MN Woodford, KJ Usdin, K TI DNA secondary structures and the evolution of hypervariable tandem arrays SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID POLYMORPHIC REGION ADOPTS; MOUSE MINISATELLITE LOCUS; REPETITIVE NONCODING DNA; TELOMERE-BINDING-PROTEIN; FRAGILE-X SYNDROME; TRINUCLEOTIDE REPEAT; CGG REPEAT; SPONTANEOUS MUTATION; SOMATIC MUTATION; TRIPLET REPEAT AB Tandem repeats are ubiquitous in nature and constitute a major source of genetic variability in populations. This variability is associated with a number of genetic disorders in humans including triplet expansion diseases such as Fragile X syndrome and Huntington's disease. The mechanism responsible for the variability/instability of these tandem arrays remains contentious. We show here that formation of secondary structures, in particular intrastrand tetraplexes, is an intrinsic property of some of the more unstable arrays. Tetraplexes block DNA polymerase progression and may promote instability of tandem arrays by increasing the likelihood of reiterative strand slippage. In the course of doing this work we have shown that some of these tetraplexes involve unusual base interactions. These interactions not only generate tetraplexes with novel properties but also lead us to conclude that the number of sequences that can form stable tetraplexes might be much larger than previously thought. C1 NIDDK,SECT GENOM STRUCT & FUNCT,CELLULAR & MOL BIOL LAB,NIH,BETHESDA,MD 20892. NR 73 TC 56 Z9 57 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 APR 4 PY 1997 VL 272 IS 14 BP 9517 EP 9523 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WU037 UT WOS:A1997WU03700098 PM 9083093 ER PT J AU Shearer, GM Chougnet, C Shearer, MS AF Shearer, GM Chougnet, C Shearer, MS TI Atopic disease and immunologic response SO SCIENCE LA English DT Letter ID CELLS RP Shearer, GM (reprint author), NCI,BETHESDA,MD 20817, USA. NR 11 TC 2 Z9 2 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 APR 4 PY 1997 VL 276 IS 5309 BP 17 EP 18 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA WR386 UT WOS:A1997WR38600004 PM 9122696 ER PT J AU Rabkin, CS Janz, S Lash, A Coleman, AE Musaba, E Liotta, L Biggar, RJ Zhuang, ZP AF Rabkin, CS Janz, S Lash, A Coleman, AE Musaba, E Liotta, L Biggar, RJ Zhuang, ZP TI Monoclonal origin of multicentric Kaposi's sarcoma lesions SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID X-CHROMOSOME INACTIVATION; SPINDLE CELLS; CULTURE; VIRUS; BLOOD AB Background Kaposi's sarcoma has features of both hyperplastic proliferation and neoplastic growth. Multiple lesions, in which spindle cells are prominent, often arise synchronously over widely dispersed areas. We tested the hypothesis that the spindle cells in these multicentric lesions originate from a single clone of precursor cells. Methods To determine whether Kaposi's sarcoma is a monoclonal disorder, we assessed the methylation patterns of the androgen-receptor gene (HUMARA) in multiple lesions from women with the acquired immunodeficiency syndrome. In polyclonal tissues, about half the copies of each HUMARA allele are methylated, whereas in cells derived from a single clone all the copies of only one allele are methylated. To minimize contamination by normal DNA, we used microdissection to isolate areas composed primarily of spindle cells, the putative tumor cells. Results Eight patients with a total of 32 tumors were studied. Of these tumors, 28 had highly unbalanced methylation patterns (i.e., predominant methylation of one HUMARA allele). In all the tumors that had unbalanced methylation from a given patient, the same allele predominated. Conclusions These data indicate that Kaposi's sarcoma is a disseminated monoclonal cancer and that the changes that permit the clonal outgrowth of spindle cells occur before the disease spreads. (C) 1997, Massachusetts Medical Society. C1 NCI,GENET LAB,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. UNIV TEACHING HOSP,LUSAKA,ZAMBIA. RP Rabkin, CS (reprint author), NCI,VIRAL EPIDEMIOL BRANCH,EPN 434,BETHESDA,MD 20892, USA. OI Lash, Alex/0000-0003-3787-1590 NR 23 TC 167 Z9 173 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 3 PY 1997 VL 336 IS 14 BP 988 EP 993 DI 10.1056/NEJM199704033361403 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA WR385 UT WOS:A1997WR38500003 PM 9077377 ER PT J AU Merke, DP Cutler, GB AF Merke, DP Cutler, GB TI New approaches to the treatment of congenital adrenal hyperplasia SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MALE PRECOCIOUS PUBERTY; 21-HYDROXYLASE DEFICIENCY; MUTATION; FLUTAMIDE; RECEPTOR; GENE C1 US PHS,WASHINGTON,DC. RP Merke, DP (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,NIH,BLDG 10,ROOM 10N262,10 CTR DR MSC 1862,BETHESDA,MD 20892, USA. NR 20 TC 23 Z9 24 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 APR 2 PY 1997 VL 277 IS 13 BP 1073 EP 1076 DI 10.1001/jama.277.13.1073 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA WQ089 UT WOS:A1997WQ08900034 PM 9091697 ER PT J AU Solomon, D AF Solomon, D TI Stat bite - PAP test abnormalities by diagnosis SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material RP Solomon, D (reprint author), NATL CANC INST,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 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 APR 2 PY 1997 VL 89 IS 7 BP 475 EP 475 PG 1 WC Oncology SC Oncology GA WQ603 UT WOS:A1997WQ60300013 ER PT J AU Dedrick, RL Flessner, MF AF Dedrick, RL Flessner, MF TI Pharmacokinetic problems in peritoneal drug administration: Tissue penetration and surface exposure SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID GYNECOLOGIC-ONCOLOGY-GROUP; TUMOR BLOOD-FLOW; OVARIAN-CANCER; INTRAPERITONEAL THERAPY; SOLUTE TRANSPORT; MASS-TRANSFER; DIALYSIS; CISPLATIN; HYPERGLYCEMIA; CHEMOTHERAPY AB Both theory and clinical studies demonstrate that drug concentrations in the peritoneal cavity can greatly exceed concentrations in the plasma following intraperitoneal administration. This regional advantage has been associated with clinical activity, including surgically documented complete responses in ovarian cancer patients with persistent or recurrent disease following systemic therapy, and has produced a survival advantage in a recent phase III trial, Two pharmacokinetic problems appear to limit the effectiveness of intraperitoneal therapy: poor tumor penetration by the drug and incomplete irrigation of serosal surfaces by the drug-containing solution. We have examined these problems in the context of a very simple, spatially distributed model, If D is the diffusivity of the drug in a tissue adjacent to the peritoneal cavity and k is the rate constant for removal of the drug from the tissue by capillary blood, the model predicts that (for slowly reacting drugs) the characteristic penetration distance is (D/k)(1/2) and the apparent permeability of the surface of a peritoneal structure is (Dk)(1/2). The permeability-area product used in classical pharmacokinetic calculations for the peritoneal cavity as a whole is the sum of the products of the tissue-specific permeabilities and the relevant superficial surface areas, Since the model is mechanistic, it provides insight into the expected effect of procedures such as pharmacologic manipulation or physical mixing, We observe that large changes in tissue penetration may be difficult to achieve but that we have very little information on the transport characteristics within tumors in this setting or their response to vasoactive drugs, Enhanced mixing is likely to offer significant potential for improved therapy; however, procedures easily applicable to the clinical setting have not been adequately investigated and should be given high priority, Clinical studies indicate that an increase in irrigated area may be achieved in many patients by individualizing the dialysate volume and consideration of patient position. C1 UNIV ROCHESTER,MED CTR,DEPT MED,ROCHESTER,NY 14642. RP Dedrick, RL (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BLDG 13,RM 3N17,BETHESDA,MD 20892, USA. NR 61 TC 137 Z9 137 U1 1 U2 11 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 APR 2 PY 1997 VL 89 IS 7 BP 480 EP 487 DI 10.1093/jnci/89.7.480 PG 8 WC Oncology SC Oncology GA WQ603 UT WOS:A1997WQ60300006 PM 9086004 ER PT J AU Bossuyt, X Blanckaert, N Fieisher, T AF Bossuyt, X Blanckaert, N Fieisher, T TI Current approaches to histocompatibility testing - A short overview. SO ACTA CLINICA BELGICA LA English DT Article ID UNRELATED DONORS; PCR-SSP; MARROW TRANSPLANTS; KIDNEY-TRANSPLANTS; HLA; ALLELES; SELECTION; SSOP RP Bossuyt, X (reprint author), NIH,SERV IMMUNOL,CTR CLIN,BLDG 10,RM 2C-410,BETHESDA,MD 20892, USA. NR 26 TC 0 Z9 0 U1 0 U2 0 PU ACTA CLINICA BELGICA PI BRUSSELS PA JARDIN MARTIN V, 69, BP 41/4375, 1200 BRUSSELS, BELGIUM SN 0001-5512 J9 ACTA CLIN BELG JI Acta Clin. Belg. PD APR PY 1997 VL 52 IS 2 BP 92 EP 98 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA XC781 UT WOS:A1997XC78100005 PM 9204584 ER PT J AU Repo, E Virkkunen, M Rawlings, R Linnoila, M AF Repo, E Virkkunen, M Rawlings, R Linnoila, M TI Criminal and psychiatric histories of Finnish arsonists SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE arson; enuresis; criminal recidivism; alcohol dependence; antisocial personality disorder ID IMPULSIVE FIRE SETTERS; CEREBROSPINAL-FLUID; VIOLENT OFFENDERS; FIRESETTERS; RECIDIVISM; MEN AB We investigated psychiatric and demographic variables and lifetime criminality among arsonists referred for a pre-trial psychiatric assessment. The medical and criminal records of 282 arsonists were studied in order to compare first-time and repeat offenders with regard to diagnostic, demographic and biological variables. Alcohol dependence and antisocial personality disorder were common among recidivist offenders. This finding was especially prominent among offenders who committed violent crimes. Recidivist offenders commonly had a history of long-lasting enuresis during their childhood. They were younger at the time of their first offence, and were more often intoxicated with alcohol during the arson attempt. Among arsonists, lifetime criminal recidivism was primarily associated with alcohol dependence and antisocial personality disorder. Psychosis was a common diagnosis among subjects who had no record of recidivist criminal offences. C1 NIAAA,CLIN STUDIES LAB,BETHESDA,MD 20892. RP Repo, E (reprint author), UNIV HELSINKI,CENT HOSP,DEPT FORENS PSYCHIAT,FIN-00180 HELSINKI,FINLAND. NR 37 TC 40 Z9 40 U1 1 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD APR PY 1997 VL 95 IS 4 BP 318 EP 323 DI 10.1111/j.1600-0447.1997.tb09638.x PG 6 WC Psychiatry SC Psychiatry GA WX147 UT WOS:A1997WX14700009 PM 9150826 ER PT J AU Orenstein, JM Alkan, S Blauvelt, A Jeang, KT Weinstein, MD Ganem, D Herndier, B AF Orenstein, JM Alkan, S Blauvelt, A Jeang, KT Weinstein, MD Ganem, D Herndier, B TI Visualization of human herpesvirus type 8 in Kaposi's sarcoma by light and transmission electron microscopy SO AIDS LA English DT Article DE Kaposi's sarcoma-associated herpesvirus; human herpesvirus type 8; transmission electron microscopy; Kaposi's sarcoma; light microscopy; in situ hybridization ID ACQUIRED IMMUNODEFICIENCY SYNDROME; EPSTEIN-BARR-VIRUS; HUMAN CYTOMEGALOVIRUS; DNA-SEQUENCES; CELL-LINES; INFECTION; DISEASE; AIDS; REPLICATION; PARTICLES AB Background: Human herpesvirus type 8 (HHV-8) has been associated with Kaposi's sarcoma, body cavity-based lymphoma (BCBL), and multicentric Castleman's disease through DNA, in situ hybridization, and serologic studies. HHV-8 has been visualized only in HHV-8-positive/Epstein-Barr virus (EBV)-negative/ cytomegalovirus (CMV)-negative BCBL cell lines, but not in HHV-8-positive/EBV-negative/CMV-negative Kaposi's sarcoma lesions. Design: Kaposi's sarcoma of the skin, lymph node, and spleen from three patients with AIDS were analysed for HHV-8, EBV and CMV DNA by polymerase chain reaction (PCR), for HHV-8 RNA (T1.1 riboprobe) by in situ hybridization (ISH), for viral inclusions by light microscopy, and for herpesviruses by transmission electron microscopy (TEM). Sections were also labeled with T1.1 counterstained with CD34, an endothelial cell marker. Results: The skin lesion was DNA PCR-positive for HHV-8 and CMV (nested, but not single PCR), the lymph node was positive for HHV-8 and EBV, and the spleen was positive for only HHV-8. TEM revealed infection by a virus displaying the typical morphology and cytopathicity of herpesviruses. Hexagonal nucleocapsids and mature enveloped virions were present in vasoformative spindle cells and mononuclear cells, often resembling lymphocytes. Extrapolating from TEM to standard light microscopy on hematoxylin and eosin-stained paraffin sections, eosinophilic, targetoid intranuclear inclusions were identified within spindle cells which often lined vascular lumina. The T1.1-riboprobe labeled CD34+ spindle cells containing intranuclear inclusions, as well as mononuclear cells within Kaposi's sarcoma and residual lymphoid tissue. Conclusion: The herpesvirus visualized in Kaposi's sarcoma lesions has morphologic and cytopathic features typical of human herpesviruses, productively infects vasoformative spindle cells and mononuclear cells, and is consistent with HHV-8. It can also form intranuclear inclusions that are identifiable by light microscopy in hematoxylin and eosin sections and by ISH. C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NIAID,MOL MICROBIOL LAB,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DEPT PATHOL,SAN FRANCISCO,CA. UNIV CALIF SAN FRANCISCO,HOWARD HUGHES MED INST,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT MICROBIOL,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT IMMUNOL,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94143. RP Orenstein, JM (reprint author), GEORGE WASHINGTON UNIV,MED CTR,DEPT PATHOL,ROSS 502,2300 EYE ST NW,WASHINGTON,DC 20037, USA. RI Jeang, Kuan-Teh/A-2424-2008 FU NCI NIH HHS [R01 CA73534]; NIDCR NIH HHS [N01-DE-12585] NR 43 TC 67 Z9 68 U1 0 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD APR PY 1997 VL 11 IS 5 BP F35 EP F45 DI 10.1097/00002030-199705000-00001 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA WQ511 UT WOS:A1997WQ51100001 PM 9108935 ER PT J AU Allen, JP Fertig, JB Litten, RZ Sillanaukee, P Anton, RF AF Allen, JP Fertig, JB Litten, RZ Sillanaukee, P Anton, RF TI Proposed recommendations for research on biochemical markers for problematic drinking SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE biochemical markers; carbohydrate-deficient transferrin; alcohol research methodology; research design AB Biochemical markers can serve as valuable tools in screening for problematic drinking, determining whether a health problem is likely alcohol related, and monitoring alcoholics for relapse during and after treatment, Furthermore, biochemical markers can assist in forensic investigations; in identification of public health, safety, and transportation workers who may drink excessively and who, as a result, may put others at risk; in evaluation of efficacy of treatments for alcohol abuse; and in recognition of early phase alcohol-related tissue damage. Within all of these contexts, a biochemical marker or set of markers may corroborate verbal reports or may provide valuable independent information on alcohol use when an individual is unable or unwilling to offer valid data about alcohol consumption. C1 NIAAA,BETHESDA,MD. PHARMACIA DIAGNOST AB,S-75182 UPPSALA,SWEDEN. MED UNIV S CAROLINA,CHARLESTON,SC 29425. NR 11 TC 15 Z9 15 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD APR PY 1997 VL 21 IS 2 BP 244 EP 247 DI 10.1097/00000374-199704000-00010 PG 4 WC Substance Abuse SC Substance Abuse GA WU258 UT WOS:A1997WU25800010 PM 9113259 ER PT J AU Kondo, Y Ipsen, H Lowenstein, H Karpas, A Hsieh, LS AF Kondo, Y Ipsen, H Lowenstein, H Karpas, A Hsieh, LS TI Comparison of concentrations of Cry j 1 and Cry j 2 in diploid and triploid Japanese cedar (Cryptomeria japonica) pollen extracts SO ALLERGY LA English DT Article DE Cry j 1; Cry j 2; Japanese cedar or sugi (Cryptomeria japonica); major allergen; pollinosis; triploid ID MAJOR ALLERGEN AB Japanese cedar (Cryptomeria japonica) pollinosis has been a serious allergic disease in Japan. There are two kinds of Japanese cedar trees; the popular one is diploid, the less popular is triploid. These trees are not very different morphologically. However, the relative allergenicity of their pollens is unknown, although both major allergens, Cry j 1 and Cry j 2, have been purified and cloned from the diploid line. Triploid trees are sterile and the allergenicity of their pollen may differ. Using Japanese-cedar-allergic patient sera, we compared the concentration of these two major allergens in both kinds of pollen. Pollen collected from different years and regions was also studied. The results indicate that triploid tree pollen extract has lower concentrations of both major allergens; therefore, the pollen may be less allergenic. C1 FDA,CBER,DAPP,HFM 422,ROCKVILLE,MD 20852. FUJITA HLTH UNIV,SCH MED,DEPT PEDIAT,TOYOAKE,AICHI 47011,JAPAN. ALK LAB,HORSHOLM,DENMARK. NICHHD,DEV & MOL IMMUN LAB,NIH,BETHESDA,MD. NR 13 TC 8 Z9 8 U1 0 U2 0 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 PD APR PY 1997 VL 52 IS 4 BP 455 EP 459 DI 10.1111/j.1398-9995.1997.tb01029.x PG 5 WC Allergy; Immunology SC Allergy; Immunology GA XA221 UT WOS:A1997XA22100019 PM 9188931 ER PT J AU Dries, DL Domanski, MJ Waclawiw, MA Gersh, BJ AF Dries, DL Domanski, MJ Waclawiw, MA Gersh, BJ TI Effect of antithrombotic therapy on risk of sudden coronary death in patients with congestive heart failure SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CARDIAC DEATH; ARTERY-SURGERY; DISEASE; BYPASS AB Data from epidemiologic, autopsy, Holter monitoring, and electrophysiologic studies support the hypothesis that acute myocardial ischemia, even in the absence of myocardial infarction, is a critical component of the pathophysiology of sudden coronary death. Acute myocardial ischemia superimposed upon ventricles damaged from previous infarctions has been demonstrated to enhance the generation of lethal ventricular arrhythmias. This is a retrospective analysis of 6,797 participants in the Studies of Left Ventricular Dysfunction prevention and treatment trials. Both univariate and multivariate Cox proportional-hazards modeling were used to study the association of anticoagulant and antiplatelet therapy with the risk for sudden cardiac death. The following covariates were adjusted for in the analysis: age, ejection fraction, gender, atrial fibrillation, diabetes, a history of angina, prior infarction, prior revascularization, and the regular use of beta blockers, diuretics, digoxin, antiarrhythmic agents, or enalapril. The overall incidence of sudden cardiac death per 100 patient-years of follow-vp was 2.24%. In multivariate analysis, antiplatelet and anticoagulant monotherapy each remained independently associated with a reduction in the risk of sudden cardiac death: antiplatelet therapy with a 24% reduction (relative risk [RR] 0.76; 95% confidence interval [CI] 0.61-0.95) and antiplatelet monotherapy with a 32% reduction (RR 0.68; 95% CI 0.48-0.96). Thus, in patients with moderate to severe left ventricular systolic dysfunction resulting from coronary artery disease, antiplatelet and anticoagulant therapy are each associated with a reduction in the risk of sudden cardiac death. (C) 1997 by Excerpta Medica, Inc. C1 NHLBI,OFF BIOSTAT RES,BETHESDA,MD 20892. GEORGETOWN UNIV HOSP,DIV CARDIOL,WASHINGTON,DC 20007. RP Dries, DL (reprint author), NHLBI,CLIN TRIALS GRP,ROCKLEDGE BLDG 2,MSC 7936,6701 ROCKLEDGE DR,BETHESDA,MD 20892, USA. NR 9 TC 53 Z9 55 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 1 PY 1997 VL 79 IS 7 BP 909 EP 913 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA WT426 UT WOS:A1997WT42600014 PM 9104905 ER PT J AU Snitker, S Larson, DE Tataranni, PA Ravussin, E AF Snitker, S Larson, DE Tataranni, PA Ravussin, E TI Ad libitum food intake in humans after manipulation of glycogen stores SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE energy metabolism; indirect calorimetry; diet; carbohydrate balance; muscle biopsy; glycogen; men ID 24-HOUR ENERGY-EXPENDITURE; DIETARY-FAT; CARBOHYDRATE BALANCE; COVERT MANIPULATION; CAFETERIA DIET; WEIGHT; MEN; DETERMINANTS; OXIDATION; SELECTION AB It is controversial whether food intake in humans is under day-to-day regulation to maintain constant body glycogen stores. In eight white males with a mean (+/- SD) age of 30 +/- 4 y, body weight of 82 +/- 20 kg, and percentage body fat of 22 +/- 5%, exercise and diets were used to produce either high (HG) or low glycogen (LG) stores in a randomized crossover design. After each treatment a vastus lateralis muscle biopsy was obtained. Subsequent ad libitum food intake was measured with an automated food-selection system during 2 d in a respiratory chamber. Despite a 46 +/- 21% difference in muscle glycogen between the two treatments, ad libitum 2-d food intakes (energy, weight, or macronutrients) were similar between treatments (HG: 23.80 +/- 4.67 MJ/d; LG: 21.20 +/- 6.73 MJ/d). However, energy intake on the second day of ad libitum feeding was negatively correlated with carbohydrate balance on the first day, adjusted for the effect of total energy intake and treatment. Adjusted carbohydrate balance on day 1 only explained 9% of the variance in energy intake on day 2. The 24-h respiratory quotient on the first day after treatment was higher after the HG than after the LG treatment: 0.94 +/- 0.04 and 0.88 +/- 0.07 (P < 0.001). The findings suggest that 1) body glycogen stores play at most a minor role in shortterm food intake regulation, and 2) in the short term, imbalances in glycogen stores are corrected by adjustments of macronutrient oxidation rates. RP Snitker, S (reprint author), NIDDKD,CLIN DIABET & NUTR SECT,4212 N 16TH ST,ROOM 5-41,PHOENIX,AZ 85016, USA. NR 26 TC 36 Z9 36 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 1997 VL 65 IS 4 BP 941 EP 946 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WQ779 UT WOS:A1997WQ77900007 PM 9094876 ER PT J AU Thompson, FE Moler, JE Freedman, LS Clifford, CK Stables, GJ Willett, WC AF Thompson, FE Moler, JE Freedman, LS Clifford, CK Stables, GJ Willett, WC TI Register of dietary assessment calibration-validation studies: A status report SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Proceedings of a Symposium / 2nd International Conference on Dietary Assessment Methods CY JAN 22-24, 1995 CL BOSTON, MA DE validation; calibration; dietary assessment; dietary surveys; food-frequency questionnaire; food records; 24-h dietary recall ID FOOD-FREQUENCY QUESTIONNAIRE; ASSESSMENT INSTRUMENTS; PLASMA CAROTENOIDS; ENERGY-INTAKE; NHANES-III; REPRODUCIBILITY; VALIDITY; RECORDS; CHILDREN; WOMEN AB A register of dietary assessment calibration-validation studies was created to improve communication between investigators, avoid duplication of effort, and identify gaps in knowledge. Calibration-validation studies were defined as investigations in which the participants completed al least two different dietary measurements. A questionnaire soliciting descriptive information about such studies was widely distributed. Completed questionnaires were received from October 1993 through September 1994 and the data from them were entered into a computer database. Preliminary individual reports were mailed to all contributors in September 1994 for revision or updating. Responses received by the end of October 1994 were incorporated into the database; A status report was published in December 1994. The report includes descriptions of 84 studies, 15 summary tables, and 6 reference indexes. Of the 84 studies included, 44 (52%) were conducted in North America, 35 (42%) in Europe, 2 (2%) in South America, 2 (2%) in Asia, and 1 (1%) in Australia. Sixty-three of the 84 studies (75%) used food-frequency questionnaires, 52 (62%) used food records, 35 (42%) used one or more dietary recalls, 11 (13%) used biological measures, and 8 (10%) used diet histories. Plans for maintaining and updating the register are being developed. C1 INFORMAT MANAGEMENT SERV INC, ROCKVILLE, MD USA. HARVARD UNIV, SCH PUBL HLTH, DEPT NUTR, BOSTON, MA 02115 USA. RP Thompson, FE (reprint author), NCI, DIV CANC PREVENT & CONTROL,ARB,EXECUT PLAZA N, ROOM 313,6130 EXECUT BLVD, MSC 7344, BETHESDA, MD 20892 USA. NR 52 TC 20 Z9 20 U1 1 U2 2 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 APR PY 1997 VL 65 IS 4 SU S BP 1142 EP 1147 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WR606 UT WOS:A1997WR60600009 ER PT J AU Carroll, RJ Pee, D Freedman, LS Brown, CC AF Carroll, RJ Pee, D Freedman, LS Brown, CC TI Statistical design of calibration studies SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Proceedings of a Symposium / 2nd International Conference on Dietary Assessment Methods CY JAN 22-24, 1995 CL BOSTON, MA DE calibration studies; food diaries; food-frequency questionnaires; measurement error; 24-h recalls; study design; food record; sample size ID FOOD FREQUENCY QUESTIONNAIRE; TRUE AVERAGE INTAKE; DIET AB We investigated some design aspects of calibration studies. The specific situation addressed was one in which a large group is evaluated with a food-frequency questionnaire and a smaller calibration study is conducted through use of repeated food records or recalls, with the subjects in the calibration study constituting a random sample of those in the large group. In designing a calibration study, one may use large sample sizes and few food records per individual or smaller samples and more records per subject. Neither strategy is always preferable. Instead, the optimal method for a given study depends on the survey instrument used (24-h recalls or multiple-day food records) and the variables of interest. C1 INFORMAT MANAGEMENT SERV INC, ROCKVILLE, MD USA. NCI, DIV CANC PREVENT & CONTROL, BIOMETRY BRANCH, BETHESDA, MD 20892 USA. RP Carroll, RJ (reprint author), TEXAS A&M UNIV, DEPT STAT, COLLEGE STN, TX 77843 USA. NR 9 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 1997 VL 65 IS 4 SU S BP 1187 EP 1189 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WR606 UT WOS:A1997WR60600017 ER PT J AU Freedman, LS Kipnis, V Brown, CC Schatzkin, A Wacholder, S Hartman, AM AF Freedman, LS Kipnis, V Brown, CC Schatzkin, A Wacholder, S Hartman, AM TI Adjustment for total energy intake in epidemiologic studies - Comments SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Proceedings of a Symposium / 2nd International Conference on Dietary Assessment Methods CY JAN 22-24, 1995 CL BOSTON, MA DE energy; epidemiology; methods; nutrient; nutritional; energy adjustment AB Willett et al [Am J Clin Nutr 1997;65(suppl): 1220S-8S] reviewed the case for energy adjustment in the analysis of nutritional studies and argued strongly for basing the main analysis on an energy-adjustment statistical model. They recommended focusing attention on a statistical association that represents the change in disease incidence associated with the substitution of energy from a specific nutrient for energy from other nutrient sources, while keeping total energy intake constant. Although we agree with many of the points made in their paper, we recommend assessing and reporting associations representing not only the substitution but also the addition of energy from the specific nutrient. For these ''addition'' associations, it is especially important to check for confounding with measures of body size and physical activity. Restricting analyses to substitution associations will confine investigators to estimating the relative effects of one nutrient to another and will preclude investigating the effects of increased intake of a specific nutrient. C1 NCI, DIV CANC PREVENT & CONTROL, CANC PREVENT STUDIES BRANCH, BETHESDA, MD 20892 USA. NCI, DIV CANC PREVENT & CONTROL, APPL RES BRANCH, BETHESDA, MD 20892 USA. NCI, BIOSTAT BRANCH, DIV CANC EPIDEMIOL & GENET, BETHESDA, MD 20892 USA. RP Freedman, LS (reprint author), NCI, DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH, ROOM 344,EXECUT PLAZA N, 6130 EXECUT BLVD, BETHESDA, MD 20892 USA. NR 7 TC 13 Z9 13 U1 2 U2 5 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 APR PY 1997 VL 65 IS 4 SU S BP 1229 EP 1231 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WR606 UT WOS:A1997WR60600025 ER PT J AU Cleveland, LE Cook, DA KrebsSmith, SM Friday, J AF Cleveland, LE Cook, DA KrebsSmith, SM Friday, J TI Method for assessing food intakes in terms of servings based on food guidance SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Proceedings of a Symposium / 2nd International Conference on Dietary Assessment Methods CY JAN 22-24, 1995 CL BOSTON, MA DE food guide pyramid; food intakes; servings; Healthy People 2000; dietary assessment methods; grain; vegetable; meat; dairy; fruit; survey; CSFII; Continuing Survey of Food Intakes by Individuals ID UNITED-STATES; NHANES-II; PRINCIPLES; DIET AB We describe a method for comparing food intakes reported in surveys with recommendations given in the US Department of Agriculture's food guide pyramid. Such comparison was previously difficult because many foods are eaten as mixtures that cannot be categorized into pyramid food groups and because food intake data and food recommendations are expressed in different units of measurement. We developed a recipe file showing ingredients at multiple levels of breakdown and used it to disaggregate food mixtures into their ingredients so that they could be placed into pyramid food groups. Food-specific weights consistent with the pyramid definitions for serving sizes were derived from the food code book of the 1989-1991 Continuing Survey of Food Intakes by Individuals and used to develop a serving-weight file. Data collected from 8181 adults aged greater than or equal to 20 y in the survey were used to estimate the mean number of servings from pyramid food groups and percentages of the population meeting pyramid recommendations. The mean numbers of servings were close to the minimum recommendations fur the grain, vegetable, and meat groups and well below the minimum recommendations for the fruit and dairy groups. Large proportions of adults (43-72%) failed to meet the dietary recommendations. Our method has several nutrition monitoring and nutrition education applications. C1 USDA ARS, RIVERDALE, MD USA. NCI, BETHESDA, MD 20892 USA. NR 31 TC 72 Z9 72 U1 1 U2 5 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 APR PY 1997 VL 65 IS 4 SU S BP 1254 EP 1263 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WR606 UT WOS:A1997WR60600029 ER PT J AU KrebsSmith, SM Cleveland, LE BallardBarbash, R Cook, DA Kahle, LL AF KrebsSmith, SM Cleveland, LE BallardBarbash, R Cook, DA Kahle, LL TI Characterizing food intake patterns of American adults SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Proceedings of a Symposium / 2nd International Conference on Dietary Assessment Methods CY JAN 22-24, 1995 CL BOSTON, MA DE food patterns; diet surveys; dietary behaviors; fruit; vegetables; grains; food guide pyramid; adult; Continuing Survey of Food Intakes by Individuals; food group ID DIETARY AB Food-pattern analysis provides a way to examine diets in a multidimensional context. This study examined the diets of 8181 adults in the 1989-1991 Continuing Survey of Food Intakes by Individuals and evaluated whether they met the federal recommendations for each of five food groups. The sample was partitioned among 32 different food-intake patterns, six of which represented 44% of the population. Nutrient profiles associated with each of the patterns indicated that failure to meet one or more of the food-group recommendations was associated with nutrient inadequacy, macronutrient imbalance, or both. A reexamination of the data to account for low energy reporters did not alter these findings. The pattern of meeting all five of the food-group recommendations was among the least common, accounting for only 1% of adults' intakes. C1 USDA, RIVERDALE, MD USA. NCI, BETHESDA, MD 20892 USA. INFORMAT MANAGEMENT SERV INC, SILVER SPRING, MD USA. NR 23 TC 41 Z9 41 U1 1 U2 1 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 APR PY 1997 VL 65 IS 4 SU S BP 1264 EP 1268 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WR606 UT WOS:A1997WR60600030 ER PT J AU Marshall, JR Lanza, E Bloch, A Caan, B Caggiula, A Quandt, S Iber, F Kikendall, W Slattery, M Sowell, A AF Marshall, JR Lanza, E Bloch, A Caan, B Caggiula, A Quandt, S Iber, F Kikendall, W Slattery, M Sowell, A TI Indexes of food and nutrient intakes as predictors of serum concentrations of nutrients: The problem of inadequate discriminant validity SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Proceedings of a Symposium / 2nd International Conference on Dietary Assessment Methods CY JAN 22-24, 1995 CL BOSTON, MA DE alpha-carotene; beta-carotene; vitamin E; alpha-tocopherol; validity; food-frequency questionnaire; discriminant validity; convergent validity ID FREQUENCY QUESTIONNAIRE; BETA-CAROTENE; ALPHA-TOCOPHEROL; CANCER; MEN; DATABASE; DIET; FAT AB Nutrient indexes derived from food-frequency questionnaires have generally been regarded as acceptably valid for epidemiologic purposes. Evaluations of these indexes, however, have considered only their convergent validity. We suggest that discriminant validity, or the ability to distinguish among exposures to different nutrients, is also important. Using baseline data from a large clinical trial, we tested the discriminant validity of indexes of intake of vitamin E, alpha-carotene, and beta-carotene. Our results suggest that the vitamin E index possesses neither convergent nor discriminant validity, the alpha-carotene index adequate convergent and discriminant validity, and the beta-carotene index adequate convergent but no discriminant validity. C1 SUNY BUFFALO, SCH MED & BIOMED SCI, DEPT SOCIAL & PREVENT MED, BUFFALO, NY 14260 USA. NCI, BETHESDA, MD 20892 USA. MEM SLOAN KETTERING CANC CTR, NEW YORK, NY 10021 USA. KAISER FDN RES INST, OAKLAND, CA USA. UNIV PITTSBURGH, PITTSBURGH, PA 15260 USA. WAKE FOREST UNIV, WINSTON SALEM, NC 27109 USA. EDWARD HINES JR VET ADM HOSP, HINES, IL 60141 USA. WALTER REED ARMY MED CTR, WASHINGTON, DC 20307 USA. UNIV UTAH, SALT LAKE CITY, UT USA. CTR DIS CONTROL & PREVENT, ATLANTA, GA USA. RP Marshall, JR (reprint author), UNIV ARIZONA, ARIZONA CANC CTR, 1515 N CAMPBELL AVE, POB 245024, TUCSON, AZ 85724 USA. NR 31 TC 13 Z9 13 U1 14 U2 14 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 APR PY 1997 VL 65 IS 4 SU S BP 1269 EP 1274 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WR606 UT WOS:A1997WR60600031 ER PT J AU Caan, B Schaffer, D Coates, A AF Caan, B Schaffer, D Coates, A TI Effect of nutritionist review of a self-administered food-frequency questionnaire SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Meeting Abstract DE food-frequency questionnaire; polyp prevention trial; 4-d food record; nutritionist review C1 KAISER PERMANENTE MED CARE PROGRAM, DIV RES, OAKLAND, CA 94611 USA. NCI, ROCKVILLE, MD USA. WESTAT CORP, ROCKVILLE, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 1997 VL 65 IS 4 SU S BP 1296 EP 1297 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WR606 UT WOS:A1997WR60600040 ER PT J AU Potischman, N Carroll, RJ Swanson, CA Coates, RJ Crapo, L Mittl, B Rosenthal, J Wolfe, T AF Potischman, N Carroll, RJ Swanson, CA Coates, RJ Crapo, L Mittl, B Rosenthal, J Wolfe, T TI Twenty-four-hour recalls and diet records: Differences in dietary intakes and other methodologic considerations SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Meeting Abstract DE breast cancer; 24-h recall; telephone; 3-d diet record; women; nutrient intake; energy intake C1 NCI, DIV CANC ETIOL, BETHESDA, MD 20892 USA. EMORY UNIV, ATLANTA, GA 30322 USA. WESTAT CORP, ROCKVILLE, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 1997 VL 65 IS 4 SU S BP 1309 EP 1310 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WR606 UT WOS:A1997WR60600082 ER PT J AU Sebring, NG Ropka, ME Anderson, RE AF Sebring, NG Ropka, ME Anderson, RE TI Consecutive-day versus alternate-day collection of food records: Differences in completeness and reported subject preference SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Meeting Abstract DE compliance; 3-d food record; consecutive days; alternate days C1 NIH, WARREN GRANT MAGNUSON CLIN CTR, DEPT NUTR, BETHESDA, MD 20892 USA. NIH, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 1997 VL 65 IS 4 SU S BP 1312 EP 1312 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WR606 UT WOS:A1997WR60600089 ER PT J AU Thompson, FE Hartman, AM AF Thompson, FE Hartman, AM TI Agreement between portion size reported on a food-frequency instrument and on multiple food records SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Meeting Abstract DE portion size; estimate; Health Habits and History Questionnaire; HHHQ C1 NCI, DIV CANC PREVENT & CONTROL, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 1997 VL 65 IS 4 SU S BP 1313 EP 1313 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WR606 UT WOS:A1997WR60600093 ER PT J AU Subar, AF Thompson, FE Smith, AF Jobe, JB Ziegler, RG Potischman, N Schatzkin, A Hartman, A Swanson, C Kruse, L Hayes, RB Lewis, DR Harlan, LC AF Subar, AF Thompson, FE Smith, AF Jobe, JB Ziegler, RG Potischman, N Schatzkin, A Hartman, A Swanson, C Kruse, L Hayes, RB Lewis, DR Harlan, LC TI Improving food-frequency questionnaires: A qualitative approach using cognitive interviewing SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Meeting Abstract DE food-frequency questionnaire; portion size; seasonal intake; food preparation; low-fat foods; interview; frequency C1 NCI, DIV CANC PREVENT & CONTROL, BETHESDA, MD 20892 USA. STATE UNIV COLL, DEPT PSYCHOL, BINGHAMTON, NY USA. CTR DIS CONTROL & PREVENT, NATL CTR HLTH STAT, ATLANTA, GA 30333 USA. NCI, DIV CANC ETIOL, BETHESDA, MD 20892 USA. NR 0 TC 3 Z9 3 U1 2 U2 8 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 APR PY 1997 VL 65 IS 4 SU S BP 1317 EP 1318 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WR606 UT WOS:A1997WR60600106 ER PT J AU Hartman, AM Freedman, LS Carroll, RJ Barrett, MJ AF Hartman, AM Freedman, LS Carroll, RJ Barrett, MJ TI Calibrating food-frequency questionnaires: A comparison of three studies SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Meeting Abstract DE food-frequency questionnaire; food record; true intake; estimates; calibration C1 NCI, DIV CANC PREVENT & CONTROL, BETHESDA, MD 20892 USA. TEXAS A&M UNIV, DEPT STAT, COLLEGE STN, TX 77843 USA. INFORMAT MANAGEMENT SERV INC, SILVER SPRING, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 1997 VL 65 IS 4 SU S BP 1328 EP 1328 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WR606 UT WOS:A1997WR60600133 ER PT J AU Crapo, L Mittl, E Sinha, R AF Crapo, L Mittl, E Sinha, R TI Effect of meat-preparation method on yielded weights and implications for dietary assessment SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Meeting Abstract DE meat; doneness; cooking method; carcinogen; cancer C1 NCI, NIH, BETHESDA, MD 20892 USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 1997 VL 65 IS 4 SU S BP 1331 EP 1332 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WR606 UT WOS:A1997WR60600143 ER PT J AU Sinha, R Rothman, N Swanson, C Brown, E Levander, O Knize, M Felton, J Hsu, CH Greenberg, A AF Sinha, R Rothman, N Swanson, C Brown, E Levander, O Knize, M Felton, J Hsu, CH Greenberg, A TI Development of a dietary questionnaire and databases to assess exposure to heterocyclic aromatic amine and polycyclic aromatic hydrocarbon SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Meeting Abstract DE Health Habits and History Questionnaire; database; carcinogen; heterocyclic aromatic amine; polycyclic aromatic hydrocarbon C1 NCI, NIH, BETHESDA, MD 20892 USA. LAWRENCE LIVERMORE NATL LAB, LIVERMORE, CA USA. RUTGERS STATE UNIV, NEW BRUNSWICK, NJ 08903 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 1997 VL 65 IS 4 SU S BP 1334 EP 1335 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WR606 UT WOS:A1997WR60600153 ER PT J AU Lanza, E Schatzkin, A Caan, B Weissfeld, J Cooper, R Marshall, J Shike, M Burt, R Slattery, M Iber, F Kikendall, W Mateski, D Cahill, J Brewer, B AF Lanza, E Schatzkin, A Caan, B Weissfeld, J Cooper, R Marshall, J Shike, M Burt, R Slattery, M Iber, F Kikendall, W Mateski, D Cahill, J Brewer, B TI Dietary assessment data from the Polyp Prevention Trial SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Meeting Abstract DE Polyp Prevention Trial; food-frequency questionnaire; 4-d diet record; energy intake; dietary fiber; fruit; vegetable C1 NCI, NIH, BETHESDA, MD 20892 USA. KAISER FDN, RES INST, OAKLAND, CA USA. WAKE FOREST UNIV, BOWMAN GRAY SCH MED, WINSTON SALEM, NC USA. SUNY BUFFALO, BUFFALO, NY 14260 USA. UNIV UTAH, SALT LAKE CITY, UT USA. EDWARD HINES VET ADM MED CTR, HINES, IL 60141 USA. WALTER REED ARMY MED CTR, WASHINGTON, DC 20307 USA. WESTAT CORP, ROCKVILLE, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 1997 VL 65 IS 4 SU S BP 1340 EP 1340 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WR606 UT WOS:A1997WR60600169 ER PT J AU Nebeling, LC Forman, MR Graubard, BI AF Nebeling, LC Forman, MR Graubard, BI TI Change in carotenoid intake over time: The 1987 and 1992 National Health Interview Survey SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Meeting Abstract DE carotenoid intake; alpha-carotene; beta-carotene; beta-cryptoxanthin; lutein; lycopene; change C1 NCI, DIV CANC PREVENT & CONTROL, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 1997 VL 65 IS 4 SU S BP 1361 EP 1362 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WR606 UT WOS:A1997WR60600228 ER PT J AU Koretz, DS Moscicki, EK AF Koretz, DS Moscicki, EK TI An ounce of prevention research: What is it worth? SO AMERICAN JOURNAL OF COMMUNITY PSYCHOLOGY LA English DT Editorial Material RP Koretz, DS (reprint author), NIMH,PREVENT RES BRANCH,NIH,ROOM 10-85,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 18 TC 9 Z9 9 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0091-0562 J9 AM J COMMUN PSYCHOL JI Am. J. Community Psychol. PD APR PY 1997 VL 25 IS 2 BP 189 EP 195 DI 10.1023/A:1024662228463 PG 7 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Social Work SC Public, Environmental & Occupational Health; Psychology; Social Work GA XK665 UT WOS:A1997XK66500006 PM 9226863 ER PT J AU Begtrup, K Melbye, M Biggar, RJ Goedert, JJ Knudsen, K Andersen, PK AF Begtrup, K Melbye, M Biggar, RJ Goedert, JJ Knudsen, K Andersen, PK TI Progression to acquired immunodeficiency syndrome is influenced by CD4 T-lymphocyte count and time since seroconversion SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE acquired immunodeficiency syndrome; CD4 lymphocyte count; cohort studies; HIV; homosexuality; risk factors ID HOMOSEXUAL MEN; AIDS; VIRUS; ANTIBODY; RISK; HIV AB Progression to acquired immunodeficiency syndrome (AIDS) among persons infected with human immunodeficiency virus (HIV) varies considerably and may be influenced by factors such as age, smoking, number of male partners per year, and CD4 T-lymphocyte count. The loss of CD4 lymphocytes is known to be the dominant factor in the progression to AIDS. However, it is unclear whether the effect of the CD4 lymphocyte count is of such importance that persons with similar CD4 cell counts who have been infected for widely different lengths of time have the same risk of AIDS. While a CD4 count is easily obtainable, the precise amount of time since HIV infection is in most circumstances difficult to assess. In the present analysis, 259 Danish and 245 American homosexual men were followed for up to 14 years from 1981 to 1995. Two hundred and one persons seroconverted during the study period, and 112 had developed AIDS before the end of follow-up. CD4 lymphocyte count was highly correlated with the risk of developing AIDS (p < 0.001), but AIDS risk was not affected significantly by either age at infection, smoking, or number of male partners per year (p > 0.20 in all cases), Controlled for CD4 lymphocyte count, time since seroconversion was significant in explaining the risk of AIDS (p = 0.018), with a lower risk being seen during the first 3 years after seroconversion but no effect thereafter. These data confirm the central importance of CD4 lymphocyte level in the progression of HIV disease to AIDS, and suggest that rapid progression within 3 years of infection may be related to factors other than CD4 cell count. C1 STATENS SERUM INST,DANISH EPIDEMIOL SCI CTR,DK-2300 COPENHAGEN S,DENMARK. NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. UNIV COPENHAGEN,DEPT BIOSTAT,COPENHAGEN,DENMARK. FU NCI NIH HHS [1-CP-61013] NR 16 TC 17 Z9 18 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 1 PY 1997 VL 145 IS 7 BP 629 EP 635 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WR876 UT WOS:A1997WR87600008 PM 9098180 ER PT J AU Swanson, CA Potischman, N Brinton, LA AF Swanson, CA Potischman, N Brinton, LA TI Body size and breast cancer risk among women under age 45 years - Reply SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter ID PREMENOPAUSAL WOMEN; STEROID-SECRETION; OBESE WOMEN; ESTROGENS; SERUM RP Swanson, CA (reprint author), NCI,ENVIRONM EPIDEMIOL PROGRAM,DIV CANC EPIDEMIOL & GENET,EXECUT PLAZA N,RM 443,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 10 TC 2 Z9 2 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 1 PY 1997 VL 145 IS 7 BP 669 EP 670 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WR876 UT WOS:A1997WR87600014 ER PT J AU Sonnenberg, A Everhart, JE AF Sonnenberg, A Everhart, JE TI Health impact of peptic ulcer in the United States SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID QUALITY-OF-LIFE; HELICOBACTER-PYLORI ERADICATION; DUODENAL-ULCER; DISEASE AB Objectives: To assess the general outcome and impact of current and previous peptic ulcer disease on health status in the United States. Methods: During the National Health Interview Survey of 1989, a special questionnaire on digestive diseases was administered to 41,457 randomly selected individuals. Various measures of impaired health in ulcer patients were expressed by their age- and sex-standardized prevalence rates. Results: Ten to 15% of an subjects with a recent ulcer reported that they had been in poor health, incapable of major activity, or unable to work for some time during the 12 months preceding the interview. Twenty to 25% of the subjects with recent ulcers complained about restricted activity and had spent 7 or more days per year in bed, About 40% of all ulcer subjects had seen a physician five or more times within 12 months before the interview. These percentages were significantly lower in patients with previous ulcer histories but no active ulcer within 12 months, but they were still significantly higher than in subjects with no nicer history at all. In the United States, expenditures attributed to recent ulcers amounted to $5.65 billion per year. Conclusions: In the United States, peptic ulcer disease is associated with major morbidity. Ulcer cure would result in large economic and medical savings. C1 UNIV NEW MEXICO,ALBUQUERQUE,NM 87131. NIDDKD,BETHESDA,MD 20892. RP Sonnenberg, A (reprint author), DEPT VET AFFAIRS MED CTR,2100 RIDGECREST DR SE,ALBUQUERQUE,NM 87108, USA. NR 29 TC 66 Z9 67 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD APR PY 1997 VL 92 IS 4 BP 614 EP 620 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA WV786 UT WOS:A1997WV78600012 PM 9128309 ER PT J AU Ehmann, WC Rabkin, CS Eyster, ME Goedert, JJ AF Ehmann, WC Rabkin, CS Eyster, ME Goedert, JJ TI Thrombocytopenia in HIV-infected and uninfected hemophiliacs SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE hemophiliacs; thrombocytopenia; HIV infection; survival ID HUMAN-IMMUNODEFICIENCY-VIRUS; NATURAL-HISTORY; HOMOSEXUAL MEN; INDIVIDUALS; PREDICTORS; MORTALITY; COHORT; COUNTS; AIDS AB To determine the incidence and prognostic significance of thrombocytopenia among hemophiliacs, we analyzed clinical and hematologic data from the Multicenter Hemophilia Cohort study. Nineteen percent of HIV-infected subjects had thrombocytopenia (platelet count of <100,000/mm(3)) noted at least once, compared to 3% of HIV-uninfected subjects. For HIV-infected subjects, the prevalence of thrombocytopenia rose in the first 5 years after seroconversion and was twice as common in subjects age >35 years compared to younger subjects. The risk increased after an AIDS-defining illness, particularly among older subjects, nearly one-half of whom had thrombocytopenia within 1 year after AIDS. When adjusted for age and CD4-positive lymphocyte counts, thrombocytopenia was associated with an increased risk of death [relative risk (RR) 1.7, 95%Cl = 1.2-2.3] but with little change in the risk of progression to AIDS (RR = 1.2, 95%Cl = 0.8-1.7), Treatment with zidovudine was associated with a decreased risk of thrombocytopenia (RR = 0.5, 95%Cl = 0.3-0.7). Although 59 HIV-infected subjects died of hemorrhage, only 11 (19%) of the 59 had a reported platelet count of <50,000/mm(3), and only 2 (3%) of the deaths were temporally associated with thrombocytopenia. Thus, the risk of death was increased for thrombocytopenic HIV-infected hemophiliacs hut this was not explained by an increased risk of developing AIDS and was rarely associated with death from bleeding. (C) 1997 Wiley-Liss, Inc. C1 NCI,VIRAL EPIDEMIOL BRANCH,ROCKVILLE,MD. RP Ehmann, WC (reprint author), PENN STATE UNIV,COLL MED,DEPT MED,DIV HEMATOL,HERSHEY,PA 17033, USA. NR 13 TC 11 Z9 11 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD APR PY 1997 VL 54 IS 4 BP 296 EP 300 DI 10.1002/(SICI)1096-8652(199704)54:4<296::AID-AJH6>3.0.CO;2-Q PG 5 WC Hematology SC Hematology GA WR458 UT WOS:A1997WR45800006 PM 9092684 ER PT J AU Merryman, P Cullinane, A Horne, MK AF Merryman, P Cullinane, A Horne, MK TI Siliconized glass versus polypropylene to reduce in vitro platelet activation SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Letter ID BLOOD COLLECTION; THEOPHYLLINE; DIPYRIDAMOLE; ADENOSINE RP Merryman, P (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,HEMATOL SECT,DEPT CLIN PATHOL,BETHESDA,MD 20892, USA. NR 3 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 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD APR PY 1997 VL 54 IS 4 BP 343 EP 344 PG 2 WC Hematology SC Hematology GA WR458 UT WOS:A1997WR45800023 PM 9092701 ER PT J AU Shriver, MD Smith, MW Jin, L Marcini, A Akey, JM Deka, R Ferrell, RE AF Shriver, MD Smith, MW Jin, L Marcini, A Akey, JM Deka, R Ferrell, RE TI Ethnic-affiliation estimation by use of population-specific DNA markers SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID STEPWISE MUTATION MODEL; LINKAGE DISEQUILIBRIUM; LOCI; MITOCHONDRIAL; POLYMORPHISMS; FREQUENCY; ORIGINS; RACE AB During the past 10 years, DNA analysis has revolutionized the determination of identity in a forensic context. Statements about the biological identity of two human DNA samples now can be made with complete confidence. Although DNA markers are very powerful for distinguishing among individuals, most offer little power to distinguish ethnicity or to support any statement about the physical characteristics of an individual. Through a search of the literature and of unpublished data on allele frequencies we have identified a panel of population-specific genetic markers that enable robust ethnic-affiliation estimation for major U.S. resident populations. In this report, we identify these loci and present their levels of allele-frequency differential between ethnically defined samples, and we demonstrate, using log-likelihood analysis, that this panel of markers provides significant statistical power for ethnic-affiliation estimation. In addition to their use in forensic ethnic-affiliation estimation, population-specific genetic markers are very useful in both population- and individual-level admixture estimation and in mapping genes by use of the linkage disequilibrium created when populations hybridize. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD. STANFORD UNIV,SCH MED,DEPT GENET,STANFORD,CA 94305. RP Shriver, MD (reprint author), UNIV PITTSBURGH,DEPT HUMAN GENET,130 DE SOTO ST,PITTSBURGH,PA 15235, USA. RI Smith, Michael/B-5341-2012; Jin, Li/C-1468-2009 OI Jin, Li/0000-0002-4546-2415 FU NIGMS NIH HHS [GM-45861] NR 28 TC 240 Z9 251 U1 5 U2 25 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR PY 1997 VL 60 IS 4 BP 957 EP 964 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA WT614 UT WOS:A1997WT61400026 PM 9106543 ER PT J AU Omori, M Omori, N Evarts, RP Teramoto, T Thorgeirsson, SS AF Omori, M Omori, N Evarts, RP Teramoto, T Thorgeirsson, SS TI Coexpression of flt-3 ligand flt-3 and SCF/c-kit signal transduction systems in bile-duct-ligated sl and w mice SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID TYROSINE KINASE RECEPTOR; STEM-CELL FACTOR; C-KIT; HEMATOPOIETIC STEM; GROWTH-FACTOR; MURINE FLT3; PROGENITOR CELLS; HUMAN HOMOLOG; OVAL CELLS; RAT-LIVER AB Stem cell factor (SCF) and its receptor c-kit constitute an important signal transduction system regulating cell growth and differentiation in hematopoiesis, gametogenesis, and melanogenesis. Recently, we have demonstrated that both SCF and c-kit are expressed in the bile duct epithelial cells of the mt liver and are highly up-regulated during activation of the normally dormant hepatic stem cell compartment. In the present study, we used sl/sl(d) and w/w(v) mice, which have mutation of either SCF or c-kit, to study the possible involvement of the SCF/c-kit system in the bile duct proliferation. Bile duct ligation was performed to induce the Proliferation of bile duct epithelial cells. The transcripts for both SCF and c-kit were clearly increased after bile duct ligation in both control and mutant mice. Moreover, both SI and W mice responded to the bile duct ligation, similar to the control mice, by developing new bile ducts. Recently, a novel tyrosine kinase receptor, flt-3 receptor, has been identified in the fetal liver. It has been reported that the flt-3 ligand (FL)/flt-3 system can synergize with the SCF/c-kit system and stimulate the proliferation of hematopoietic cells. Therefore, we hypothesized that the FL/flt-3 system might compensate for the compromised SCF/c-kit system in the liver of SI and W mice. The expression of both FL and flt-3 were significantly increased in bile-duct-ligated liver from both normal and mutant mice, and the transcripts for the flt-3 receptor were selectively located on bile duct epithelial cells. Based on these results, we postulate the existence of a compensatory/additive function between the FL/flt-3 and the SCF/c-kit signal transduction systems in hepatic cell biology. C1 NCI,EXPT CARCINOGENESIS LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 42 TC 60 Z9 65 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 APR PY 1997 VL 150 IS 4 BP 1179 EP 1187 PG 9 WC Pathology SC Pathology GA WR012 UT WOS:A1997WR01200005 PM 9094974 ER PT J AU Wahl, SM Worley, P Jin, WW McNeely, TB Eisenberg, S Fasching, C Orenstein, JM Janoff, EN AF Wahl, SM Worley, P Jin, WW McNeely, TB Eisenberg, S Fasching, C Orenstein, JM Janoff, EN TI Anatomic dissociation between HIV-1 and its endogenous inhibitor in mucosal tissues SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LEUKOCYTE PROTEASE INHIBITOR; SECRETORY LEUKOPROTEASE INHIBITOR; SALIVARY-GLANDS; PROTEINASE-INHIBITOR; RESPIRATORY-TRACT; POTENT INHIBITOR; HOMOSEXUAL MEN; HTLV-III; CELLS AB The rarity of oral transmission of human immunodeficiency virus (HIV)-1 by saliva suggests the absence of HIV-1 in the oral cavity and/or the presence of viral inhibitory molecules. We analyzed salivary gland tissues from 55 individuals with acquired immune deficiency syndrome (AIDS) for the presence of HIV-1 by in situ hybridization and detected the virus in more than 30% of these salivary glands. These data, together with previous demonstrations of HIV-1 in oral secretions, implicate a key role for an antiviral molecule(s) in suppressing transmission. Thus, we focused on the characterization and localization of the endogenous antiviral molecule secretory leukocyte protease inhibitor (SLPI), which inhibits HIV-1 infection in vitro. Expression of SLPI transcripts was evident in submandibular, parotid, and minor salivary glands from both HIV-1-infected and seronegative subjects. Gene expression was reflected by similar levels of SLPI protein by immunohistochemical analysis in the tissues and by enzyme-linked immunosorbent assay in the saliva. However, although SLPI accumulated in acinar cells or ductal epithelium, HIV-1 transcripts did not, and these viral transcripts were identified only in mononuclear cells within the salivary gland stroma. By in situ hybridization, we found no evidence of productive HIV-1 infection of salivary gland epithelium. Thus, HIV-1 was frequently identified in salivary gland tissue, but the virus was found in interstitial mononuclear cells only and did not co-localize with SLPI. Once within the oral cavity, HIV-1 exposure to antiviral levels of SLPI may impede infection of additional target cells, contributing to the virtual absence of oral transmission of HIV-1 by saliva. These studies emphasize the importance of innate, endogenous inhibitors of HIV-1, particularly SLPI, as effective inhibitors of HIV-1 transmission. C1 SYNERGEN INC,BOULDER,CO 80301. UNIV MINNESOTA,SCH MED,VET AFFAIRS MED CTR,INFECT DIS SECT,MINNEAPOLIS,MN 55455. GEORGE WASHINGTON UNIV,DEPT PATHOL,WASHINGTON,DC. RP Wahl, SM (reprint author), NIDR,IMMUNOL LAB,NIH,30 CONVENT DR,MSC 4352,BLDG 30,ROOM 332,BETHESDA,MD 20892, USA. FU NIDCR NIH HHS [N01-DE-12585, N01-DE42600] NR 46 TC 33 Z9 33 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 APR PY 1997 VL 150 IS 4 BP 1275 EP 1284 PG 10 WC Pathology SC Pathology GA WR012 UT WOS:A1997WR01200015 PM 9094984 ER PT J AU Kuukasjarvi, T Tanner, M Pennanen, S Karhu, R Kallioniemi, OP Isola, J AF Kuukasjarvi, T Tanner, M Pennanen, S Karhu, R Kallioniemi, OP Isola, J TI Genetic changes in intraductal breast cancer detected by comparative genomic hybridization SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID SEQUENCE COPY NUMBER; CARCINOMA IN-SITU; DNA AMPLIFICATION; ALLELIC LOSS; PROGRESSION; TUMOR; INSITU AB Ductal carcinoma in situ (DCIS) is considered a direct precursor of invasive ductal breast cancer (IDC). We combined tissue microdissection and comparative genomic hybridization to identify genetic changes in five DCIS lesions with no invasion and in two that were adjacent to IDC. Extensive genetic changes characterized pure DCIS cases with gains of 1q, 6q, 8q, and Xq as well as losses of 17P and chromosome 22 being most often involved. Except for the Xq gain, these changes are also common to IDC. Separate analysis of DCIS and IDC components in the same tumor revealed all almost identical pattern of genetic changes in one case, whereas substantial differences were found in another. We conclude that many of the common genetic changes in IDC may take place before development of invasive growth. However, a simple linear progression model may not always account for the DCIS-IDC transition. C1 TAMPERE UNIV HOSP,DEPT PATHOL,TAMPERE,FINLAND. TAMPERE UNIV HOSP,CANC GENET LAB,TAMPERE,FINLAND. NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892. RI Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 24 TC 85 Z9 86 U1 1 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 1997 VL 150 IS 4 BP 1465 EP 1471 PG 7 WC Pathology SC Pathology GA WR012 UT WOS:A1997WR01200032 PM 9095001 ER PT J AU Bian, XP Hughes, FM Huang, Y Cidlowski, JA Putney, JW AF Bian, XP Hughes, FM Huang, Y Cidlowski, JA Putney, JW TI Roles of cytoplasmic Ca2+ and intracellular Ca2+ stores in induction and suppression of apoptosis in S49 cells SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE calcium signaling; thapsigargin; capacitative calcium entry; Bcl-2; glucocorticoids ID GLUCOCORTICOID-INDUCED LYMPHOCYTOLYSIS; CAPACITATIVE CALCIUM ENTRY; INTERNUCLEOSOMAL FRAGMENTATION; CA2+-ATPASE INHIBITOR; LEUKEMIA-CELLS; ACINAR-CELLS; DEATH; DNA; BCL-2; THAPSIGARGIN AB The Ca2+-ATPase inhibitors, thapsigargin and cyclopiazonic acid, depleted intracellular Ca2+ stores, induced large increases in intracellular Ca2+ concentration, and caused apoptosis in S49 cells. Removal of extracellular Ca2+ augmented apoptosis due to thapsigargin, indicating that depletion of Ca2+ from intracellular stores is responsible for apoptosis with this agent. Overexpression of the apoptosis suppressor, Bcl-2, inhibited apoptosis due to thapsigargin but did not affect thapsigargin-induced Ca2+ signaling. Dexamethasone induced apoptosis, diminished the size of the endoplasmic reticulum Ca2+ pool, and caused a small elevation of intracellular Ca2+. However, this elevation was not due to Ca2+ influx because the increase was similar in the presence or absence of Ca2+ in the medium. Furthermore, in contrast to the results with thapsigargin, apoptosis due to dexamethasone was unchanged in a Ca2+ free medium. These results indicate that depletion of Ca2+ stores initiates a pathway leading to apoptosis. Elevations in cytoplasmic Ca2+ appears to play a lesser role than previously thought in the actions of Bcl-2 and glucocorticoids. C1 NIEHS, CELLULAR & MOL PHARMACOL LAB, NIH, RES TRIANGLE PK, NC 27709 USA. NR 38 TC 129 Z9 132 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD APR PY 1997 VL 272 IS 4 BP C1241 EP C1249 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA WU497 UT WOS:A1997WU49700019 ER PT J AU Ding, CL Potter, ED Qiu, WP Coon, SL Levine, MA Guggino, SE AF Ding, CL Potter, ED Qiu, WP Coon, SL Levine, MA Guggino, SE TI Cloning and widespread distribution of the rat rod-type cyclic nucleotide-gated cation channel SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE lung; pineal gland; hippocampus ID FUNCTIONAL EXPRESSION; ENDOTHELIAL-CELLS; GUANYLATE-CYCLASE; NITRIC-OXIDE; ACTIVATED CHANNEL; GMP; GENE; DNA; ATRIAL; HYBRIDIZATION AB We used Northern blot analysis, ribonuclease protection assay (RPA), reverse transcriptase-polymerase chain reaction, and in situ hybridization to investigate the hypothesis that the CNG1 isoform of the cyclic nucleotide-gated nonselective cation channel may be widely distributed in tissues of the rat. A cDNA encoding the CNG1 isoform was isolated from rat eye and human retina, and partial sequences were isolated from rat pineal gland and human kidney. Northern blot analysis revealed a 3.1-kilobase (kb) CNG1 transcript in rat eye, pineal gland, pituitary, adrenal gland, and spleen, and a larger transcript of 3.5 kb was found in testis. RPA confirmed the identity of CNG1 mRNA in rat eye, lung, spleen, and brain. Polymerase chain reaction-based detection of the mRNA for CNG1 indicates that the channel is expressed in lower abundance in many other tissues, including thymus, skeletal muscle, heart, and parathyroid gland. The cellular distribution of CNG1 was further studied by in situ hybridization, which demonstrated expression of mRNA in lung, thymus, pineal gland, hippocampus, cerebellum, and cerebral cortex but not in heart or kidney. C1 JOHNS HOPKINS UNIV, SCH MED, DEPT MED, DIV GASTROENTEROL, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT MED, DIV ENDOCRINOL, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROSCI, BALTIMORE, MD 21205 USA. NIH, SECT NEUROENDOCRINOL, BETHESDA, MD 20892 USA. NR 39 TC 71 Z9 71 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD APR PY 1997 VL 272 IS 4 BP C1335 EP C1344 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA WU497 UT WOS:A1997WU49700030 ER PT J AU Ho, MWY Shears, SB Bruzik, KS Duszyk, M French, AS AF Ho, MWY Shears, SB Bruzik, KS Duszyk, M French, AS TI Ins(3,4,5,6)P-4 specifically inhibits a receptor-mediated Ca2+-dependent Cl- current in CFPAC-1 cells SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE epithelia; cystic fibrosis; calcium; chloride channel; inositol tetrakisphosphates ID CYSTIC-FIBROSIS AIRWAY; INOSITOL PHOSPHATES; CHLORIDE CHANNELS; INTRACELLULAR CALCIUM; EPITHELIAL-CELLS; ION CHANNELS; ATP; 1,3,4,5,6-PENTAKISPHOSPHATE; SECRETION; K+ AB We have examined the role of inositol 3,4,5,6-tetrakisphosphate [Ins(3,4,5,6)P-4] in the control of Cl- current in CFPAC-1 cells. Intracellular Ins(3,4,5,6)P-4 had no effect on basal current, but it produced a five- to sevenfold reduction in the Cl- current stimulated by either 2 mu M extracellular ATP or by 1 mu M extracellular thapsigargin. The half-maximally effective dose of Ins(3,4,5,6)P-4 was 2.9 mu M, and 4 mu M blocked >80% of the ATP-activated current. In contrast, 10 mu M Ins(1,4,5,6)P-4, Ins(1,3,4,5)P-4, or Ins(1,3,4,6)P-4 enhanced rather than inhibited the ATP-activated Cl- current, although Ins(1,4,5,6)P-4 only acted transiently. These stimulatory effects were Ca2+ dependent and largely inhibited by coapplication of equimolar Ins(3,4,5,6)P-4. Inositol 1,3,4,5,6-pentakisphosphate, the precursor of Ins(3,4,5,6)P-4, did not affect Cl- current. These data consolidate and extend the hypothesis that Ins(3,4,5,6)P-4 is an important intracellular regulator of Cl- current in epithelial cells. C1 DALHOUSIE UNIV, DEPT PHYSIOL & BIOPHYS, HALIFAX, NS B3H 4H7, CANADA. UNIV ALBERTA, DEPT PHYSIOL, EDMONTON, AB T6G 2H7, CANADA. NIEHS, CELLULAR & MOL PHARMACOL LAB, RES TRIANGLE PK, NC 27709 USA. UNIV ILLINOIS, DEPT MED CHEM & PHARMACOGNOSY, CHICAGO, IL 60516 USA. NR 32 TC 36 Z9 36 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD APR PY 1997 VL 272 IS 4 BP C1160 EP C1168 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA WU497 UT WOS:A1997WU49700010 ER PT J AU Moyes, CD MathieuCostello, OA Tsuchiya, N Filburn, C Hansford, RG AF Moyes, CD MathieuCostello, OA Tsuchiya, N Filburn, C Hansford, RG TI Mitochondrial biogenesis during cellular differentiation SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE cristae surface area; myogenesis; muscle; C2C12 cells; 3T3 cells ID CYTOCHROME-C-OXIDASE; RESPIRATORY-CHAIN COMPONENTS; MUSCLE ADP/ATP TRANSLOCATOR; SYNTHASE BETA-SUBUNIT; NUCLEAR GENES; MYOBLAST DIFFERENTIATION; PROTEIN-SYNTHESIS; TRANSCRIPT LEVELS; STRIATED-MUSCLE; SKELETAL-MUSCLE AB Mitochondrial biogenesis was studied during differentiation of two immortalized cell lines (C2C12, 3T3) with enzyme measurements, Northern blots, and quantitative ultrastructure. Citrate synthase, isocitrate dehydrogenase, and 3-hydroxyacyl-CoA dehydrogenase (nuclear encoded, mitochondrial matrix location) showed linear, four- to sixfold increases in enzymatic activity in C2C12 cells but increased exponentially in 3T3 cells. Cytochrome oxidase and NADH dehydrogenase (nuclear and mitochondrial encoded, cristae location) increased to a lesser extent and with a pattern dissimilar to the first group. Northern blots and activity of succinate dehydrogenase (cristae location but entirely nuclear encoded) suggested the groupings were based on location of the genes rather than the mature enzyme. However, quantitative electron microscopy and comparisons with adult tissue suggested that mitochondrial ultrastructure can influence the change in cristae enzymes. Cristae surface area per unit mitochondrial volume and per unit cell volume increased much less than did cristae enzymes. Available space on the inner membrane may become limiting and account for some aspects of the pattern of change in electron transport enzymes during differentiation. C1 UNIV CALIF SAN DIEGO, DEPT MED, LA JOLLA, CA 92093 USA. NIA, GERONTOL RES CTR, NIH, BALTIMORE, MD 21224 USA. RP Moyes, CD (reprint author), QUEENS UNIV, DEPT BIOL, KINGSTON, ON K7L 3N6, CANADA. NR 34 TC 120 Z9 123 U1 0 U2 19 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD APR PY 1997 VL 272 IS 4 BP C1345 EP C1351 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA WU497 UT WOS:A1997WU49700031 ER PT J AU Corleto, VD Severi, C Coy, DH DelleFave, G Jensen, RT AF Corleto, VD Severi, C Coy, DH DelleFave, G Jensen, RT TI Colonic smooth muscle cells possess a different subtype of somatostatin receptor from gastric smooth muscle cells SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE motility; muscle contractants; muscle relaxants; G proteins; pertussis toxin-sensitive G proteins ID GUINEA-PIG; CHOLECYSTOKININ-OCTAPEPTIDE; CHOLINERGIC TRANSMISSION; RELEASE; RAT; CONTRACTION; INHIBITION; TISSUE; ACETYLCHOLINE; RELAXATION AB Somatostatin (SS) alters colonic motility. To investigate whether SS has a direct effect on colonic smooth muscle cells, we prepared isolated muscle cells from the descending guinea pig colon and compared the effects of SS with those on isolated gastric smooth muscle cells. In gastric cells, SS had no effect on carbachol-induced contraction, whereas in colonic cells it caused inhibition. In colonic muscle cells, SS-28 caused >85% inhibition of contraction by cholecystokinin octapeptide (CCK-8), bombesin, 12-O-tetradecanoylphorbol-13-acetate, and ionomycin, whereas it had no effect on contraction by these agents in gastric cells. In gastric cells, SS inhibited relaxation. Three synthetic SS analogs had different relative affinities for causing effects in gastric and colonic cells. Pertussis toxin inhibited the action of SS-28 in each muscle cell type by 50-75%. SS-28 alone had a small contractile effect on cells from the circular layer of the colon. SS-28 inhibited carbachol-induced contraction in colonic cells from both the longitudinal and circular layers. These results demonstrate that the action of SS differs in colonic and gastric smooth muscle cells. SS inhibits contractants in colonic cells and relaxants in gastric cells. In colonic cells, SS has a weak contractile effect due to an effect on circular muscle cells and an inhibitory effect on cells from both longitudinal and circular layers. A different SS receptor subtype mediates the actions of SS in colonic and gastric muscle cells. In both cell types, the actions of SS are mediated by pertussis toxin-sensitive and -insensitive G proteins. C1 NIDDKD, NIH, DDB, BETHESDA, MD 20892 USA. TULANE UNIV, SCH MED, DEPT MED, NEW ORLEANS, LA 70112 USA. UNIV ROMA LA SAPIENZA, MED CLIN 2, DIGEST DIS UNIT, I-00161 ROME, ITALY. NR 44 TC 11 Z9 11 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD APR PY 1997 VL 272 IS 4 BP G689 EP G697 PG 9 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA WU499 UT WOS:A1997WU49900001 PM 9142897 ER PT J AU Horinaka, N Artz, N Cook, M Holmes, C Goldstein, DS Kennedy, C Sokoloff, L AF Horinaka, N Artz, N Cook, M Holmes, C Goldstein, DS Kennedy, C Sokoloff, L TI Effects of elevated plasma epinephrine on glucose utilization and blood flow in conscious rat brain SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE carbon-14-iodoantipyrine; cerebral circulation; cerebral energy metabolism; carbon-14-deoxyglucose ID INSULIN-INDUCED HYPOGLYCEMIA; DEOXYGLUCOSE METHOD; INCREASE; BARRIER; CATECHOLAMINES; HYPERGLYCEMIA; ADRENALINE; RECOVERY; INFUSION AB Acute glucoprivation increases cerebral blood flow (CBF), which is often attributed to the associated rise in plasma epinephrine levels. This study examined directly the effects of comparable increases in plasma epinephrine levels achieved by continuous intravenous infusions of epinephrine in normoglycemic, unanesthetized rats on local and overall CBF and cerebral glucose utilization (lCMR(glc)). CBF was determined by the autoradiographic [C-14]iodoantipyrine method in six unanesthetized rats in which epinephrine dissolved in 1% ascorbic acid-1 mM EDTA was infused at a rate of 1 mu g/min and in five normal controls infused with the vehicle alone. lCMR(glc) was determined by the autoradiographic [C-14]deoxyglucose method in six conscious rats infused similarly with the epinephrine solution and in six normal controls treated with the vehicle alone. The epinephrine infusions raised arterial plasma epinephrine levels 10- to 20-fold and increased arterial blood pressure and plasma glucose levels. Local CBF, however, was significantly changed (P < 0.05, Student's t-test) in only 2 of 25 structures examined, and the changes were decreases not increases. lCMR(glc) was not changed significantly in any of 42 brain structures examined, and average blood flow and glucose utilization in the brain as a whole were unaffected. These results show that high circulating levels of epinephrine similar to those accompanying glucoprivation alter neither local nor overall CBF and glucose utilization and cannot explain the increases in CBF associated with glucoprivation. C1 NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. NINDS, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. RP Sokoloff, L (reprint author), NIMH, Cerebral Metab Lab, Bldg 36,Rm 1A-05, Bethesda, MD 20892 USA. NR 30 TC 13 Z9 13 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD APR PY 1997 VL 272 IS 4 BP H1666 EP H1671 PG 6 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA WU852 UT WOS:A1997WU85200014 ER PT J AU Abrams, RM Burchfield, DJ Sun, Y Smith, CB AF Abrams, RM Burchfield, DJ Sun, Y Smith, CB TI Rates of local cerebral protein synthesis in fetal and neonatal sheep SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE fetal development; brain; leucine; amino acid recycling; myelination ID GLUCOSE-UTILIZATION; PRECURSOR POOL; DEGRADATION; METABOLISM; GROWTH; STATE; SLEEP AB During gestation there is likely to be a constantly changing rate of protein synthesis in the brain that may exhibit regional specificity. With the use of the quantitative autoradiographic L-[1-C-14]leucine method for the determination of local rates of leucine incorporation into cerebral protein (lCPS(Leu)), we have sought to characterize this important process. lCPS(Leu) was measured in nine fetal sheep (118-139 days gestational age) and five newborn lambs (1-5 days of age). In other experiments, the fraction of leucine in the precursor pool for protein synthesis in the brain derived from the arterial plasma was determined to be 0.57 +/- 0.04 (mean +/- SE) in one fetus and two lambs. This value was used in the calculation of lCPS(Leu) in 35 regions of the central nervous system, pineal body, and whole brain. Regardless of age, lCPS(Leu) was highest in the pineal body, brain stem, and hypothalamic nuclei and lowest in white matter. In sensorimotor cortex, corona radiata, pyramidal tracts, and whole brain, lCPS(Leu) was positively correlated with prenatal age (P less than or equal to 0.05). These increases in lCPS(Leu) probably reflect myelination in the cerebrum, which is known to occur in late gestation. C1 NIMH, CEREBRAL METAB LAB, BETHESDA, MD 20892 USA. UNIV FLORIDA, MED CTR, DEPT OBSTET & GYNECOL, GAINESVILLE, FL 32610 USA. UNIV FLORIDA, MED CTR, DEPT PEDIAT, GAINESVILLE, FL 32610 USA. NR 24 TC 1 Z9 1 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD APR PY 1997 VL 272 IS 4 BP R1235 EP R1244 PG 10 WC Physiology SC Physiology GA WT588 UT WOS:A1997WT58800031 PM 9140025 ER PT J AU Kishore, BK Terris, J FernandezLlama, P Knepper, MA AF Kishore, BK Terris, J FernandezLlama, P Knepper, MA TI Ultramicrodetermination of vasopressin-regulated urea transporter protein in microdissected renal tubules SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE urinary concentrating mechanism; vasopressin; urea transport; low-protein diet ID MEDULLARY COLLECTING DUCT; RAT; EXPRESSION; CLONING; NUMBER; CELL AB The vasopressin-regulated urea transporter (VRUT) is a 97-kDa protein (also called ''UT-1'') responsible for facilitated urea transport across the apical plasma membrane of inner medullary collecting duct (IMCD) cells. To determine the abundance of VRUT protein in collecting duct cells of the rat, we designed a sensitive fluorescence-based enzyme-linked immunosorbent assay capable of detecting <5 fmol of VRUT protein. In collecting duct segments, measurable VRUT was found in microdissected IMCD segments but not in other portions of the collecting duct. In the mid-IMCD, the measured level averaged 5.3 fmol/mm tubule length, corresponding to similar to 5 million copies of VRUT per cell. Thus VRUT is extremely abundant in the IMCD, accounting, in part, for the extremely high urea permeability of this segment. Feeding a low-protein diet (8% protein) markedly decreased urea clearance but did not alter the quantity of VRUT protein in the IMCD. Thus increased urea transport across the collecting duct with dietary protein restriction is not a consequence of increased expression of VRUT. Based on urea fluxes measured in the IMCD and our measurements of the number of copies of VRUT, we estimate a turnover number of greater than or equal to 0.3-1 x 10(5) s. In view of the large magnitude of this value and previously reported biophysical properties of urea transport in collecting ducts, we hypothesize that the VRUT may function as a channel rather than a carrier. C1 NHLBI, LKEM, NIH, BETHESDA, MD 20892 USA. UNIFORMED SERV UNIV HLTH SCI, DEPT PHYSIOL, BETHESDA, MD 20814 USA. NR 37 TC 17 Z9 17 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD APR PY 1997 VL 272 IS 4 BP F531 EP F537 PG 7 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA WU837 UT WOS:A1997WU83700016 PM 9140055 ER PT J AU Green, SB AF Green, SB TI The eating patterns study - The importance of practical randomized trials in communities SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID RURAL TANZANIA; IMPACT RP Green, SB (reprint author), NCI,BETHESDA,MD 20892, USA. NR 17 TC 7 Z9 7 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 APR PY 1997 VL 87 IS 4 BP 541 EP 543 DI 10.2105/AJPH.87.4.541 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WY039 UT WOS:A1997WY03900001 PM 9146424 ER PT J AU Lewis, CE Smith, DE Wallace, DD Williams, OD Bild, DE Jacobs, DR AF Lewis, CE Smith, DE Wallace, DD Williams, OD Bild, DE Jacobs, DR TI Seven-year trends in body weight and associations with lifestyle and behavioral characteristics in black and white young adults: The CARDIA study SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID UNITED-STATES ADULTS; DESCRIPTIVE EPIDEMIOLOGY; CIGARETTE-SMOKING; PHYSICAL-ACTIVITY; QUALITY-CONTROL; BLOOD-PRESSURE; SECULAR TRENDS; MASS INDEX; US ADULTS; WOMEN AB Objectives. This study estimated the amount of weight change in a biracial cohort of young adults and the separate components attributable to time-related and aging-related changes, as well as identified possible determinants of weight change. Methods. In this population-based prospective study of 18- to 30-year-old African-American and White men and women, body weight and prevalence of overweight were measured from 1985/86 to 1992/93. Results. Average weight increased over the 7 years, increases ranging from 5.2 kg (SE = 0.21, n = 811) in White women to 8.5 kg (SE = 0.3, n = 882) in African-American women. Significant time-related increases in weight, ranging from 2.0 kg (SE = 1.0) in White women to 4.8 kg (SE = 1.0, n = 711) in African-American men, accounted for 40% to 60% of the average total weight gain. Aging-related increases were also significant, ranging from 2.6 kg (SE = 0.8, n = 944) in White men to 5.0 kg (SE = 1.1) in African-American women. The prevalence of overweight increased progressively in each group. Decreased physical fitness was most strongly associated with weight gain in both sexes. Conclusions. The observed dramatic time-related weight gains, most likely due to secular (period-related) trends, are a serious public health concern. C1 UNIV ALABAMA,SCH PUBL HLTH,DEPT BIOSTAT,BIRMINGHAM,AL 35205. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,MINNEAPOLIS,MN 55455. RP Lewis, CE (reprint author), UNIV ALABAMA,SCH MED,DIV PREVENT MED,1717 11TH AVE S,ROOM 734,BIRMINGHAM,AL 35205, USA. FU NHLBI NIH HHS [N01-HC-48049, N01-HC-48047, N01-HC-48048] NR 50 TC 119 Z9 120 U1 1 U2 7 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 APR PY 1997 VL 87 IS 4 BP 635 EP 642 DI 10.2105/AJPH.87.4.635 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA WY039 UT WOS:A1997WY03900021 PM 9146444 ER PT J AU Mason, RJ Williams, MC Moses, HL Mohla, S Berberich, MA AF Mason, RJ Williams, MC Moses, HL Mohla, S Berberich, MA TI Stem cells in lung development, disease, and therapy SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Editorial Material ID ALVEOLAR EPITHELIAL-CELLS; UROGENITAL SINUS MESENCHYME; HAMSTER TRACHEAL EPITHELIUM; BASAL CELLS; TRANSGENIC MICE; MONOCLONAL-ANTIBODIES; SIGNAL-TRANSDUCTION; MECHANICAL INJURY; PRIMARY CULTURE; EGF RECEPTOR C1 NHLBI,DIV LUNG DIS,NIH,BETHESDA,MD 20892. NATL JEWISH CTR IMMUNOL & RESP MED,DENVER,CO 80206. VANDERBILT UNIV,DEPT CELL BIOL,NASHVILLE,TN 37232. BOSTON UNIV,CTR PULM,BOSTON,MA 02215. NCI,DIV CANC BIOL,NIH,BETHESDA,MD 20892. NR 68 TC 44 Z9 49 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD APR PY 1997 VL 16 IS 4 BP 355 EP 363 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA WR892 UT WOS:A1997WR89200001 PM 9115744 ER PT J AU Hall, WD Ferrario, CM Moore, MA Hall, JE Flack, JM Cooper, W Simmons, JD Egan, BM Lackland, DT Perry, M Roccella, EJ AF Hall, WD Ferrario, CM Moore, MA Hall, JE Flack, JM Cooper, W Simmons, JD Egan, BM Lackland, DT Perry, M Roccella, EJ TI Hypertension-related morbidity and mortality in the southeastern United States SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Review DE hypertension; cardiovascular disease; stroke; regional; southeast ID STAGE RENAL-DISEASE; OBESITY-INDUCED HYPERTENSION; NUTRITION EXAMINATION SURVEY; CARDIOVASCULAR RISK-FACTORS; BLOOD-PRESSURE; ADULT LIFE; ANTIHYPERTENSIVE THERAPY; PATIENT COMPLIANCE; NATIONAL-HEALTH; FOLLOW-UP AB Stroke mortality is higher in the Southeast compared with other regions of the United States. The prevalence of hypertension is also higher (black men = 35%, black women = 37.7%, white men = 26.5%, white women = 21.5%), and the proportion of patients whose hypertension is being controlled is poor, especially in white and black men. The prevalence of hypertension-related complications other than stroke is also higher in the Southeast. The five states with the highest death rates for congestive heart failure are all in the southern region. Of the 15 states with the highest rates of end-stage renal disease, 10 are in the Southeast. Obesity is very prevalent (24% to 28%) in the Southeast. Although Michigan tops the ranking for all states, 6 of the top 15 states are in the Southeast, as are 7 of the 10 states with the highest reported prevalence regarding no leisure-time physical activity. Similar to other areas of the United States, dietary sodium and saturated fat intake are high in the Southeast; dietary potassium intake appears to be relatively low. Other factors that may be associated with the high prevalence, poor control, and excess morbidity and mortality of hypertension-related complications in the Southeast include misperceptions of the seriousness of the problem, the severity of the hypertension, lack of adequate follow-up, reduced access to health care, the cost of treatment, and possibly, low birth weights. The Consortium of Southeastern Hypertension Control (COSEHC) is a nonprofit organization created in 1992 in response to a compelling need to improve the disproportionate hypertension-related morbidity and mortality throughout this region. The purpose of this position paper is to summarize the data that document the problem, the consequences, and possible causative factors. C1 EMORY UNIV,SCH MED,DEPT MED,ATLANTA,GA 30303. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. DANVILLE UROL CLIN,DANVILLE,VA. UNIV MISSISSIPPI,SCH MED,JACKSON,MS 39216. ASTRA MERCK,WAYNE,PA. N CAROLINA DEPT ENVIRONM HLTH & NAT RESOURCES,RALEIGH,NC 27611. WASHINGTON UNIV,SCH MED,ST LOUIS,MO. UNIV S CAROLINA,CHARLESTON,SC. NHLBI,BETHESDA,MD. RI Ducey, Thomas/A-6493-2011 NR 191 TC 116 Z9 119 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD APR PY 1997 VL 313 IS 4 BP 195 EP 209 DI 10.1097/00000441-199704000-00002 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA WR445 UT WOS:A1997WR44500002 PM 9099149 ER PT J AU Stolow, MA IshizuyaOka, A Su, Y Shi, YB AF Stolow, MA IshizuyaOka, A Su, Y Shi, YB TI Gene regulation by thyroid hormone during amphibian metamorphosis: Implications on the role of cell-cell and cell-extracellular matrix interactions SO AMERICAN ZOOLOGIST LA English DT Article; Proceedings Paper CT Symposium on Amphibian Metamorphosis - An Integrative Approach, at the Annual Meeting of the American-Society-of-Zoologists CY DEC 27-30, 1995 CL WASHINGTON, DC SP Amer Soc Zoologists ID SONIC-HEDGEHOG; CONNECTIVE-TISSUE; XENOPUS-LAEVIS; POLARIZING ACTIVITY; STROMELYSIN-3 GENE; SMALL-INTESTINE; EXPRESSION; DROSOPHILA; RECEPTOR; BREAST AB Amphibian metamorphosis is the developmental process initiated by thyroid hormone which transforms a tadpole into a frog. This transformation requires extensive remodeling of almost every tissue in the animal, One of the more well-studied tadpole tissues that undergoes remodeling is the small intestine, This tissue requires a shortening in length as well as internal anatomical restructuring to function in the adult frog, Briefly, the tadpole epithelial cells undergo programmed cell death (or apoptosis) and are replaced by a layer of newly formed adult epithelium. About 20 thyroid hormone-regulated genes participating in this intestinal remodeling have been identified, These genes can be divided into several groups based on the proposed functions of their products, One of these groups contains several secreted and/or signaling molecules, Most prominent among these are the Xenopus homologs of the hedgehog and stromelysin-3 genes, Based on the expression profiles and cellular localization, hedgehog appears to be involved in adult epithelial morphogenesis, Stromelysin-3 may participate in basal lamina modification which is potentially involved in the apoptosis of the larval epithelium and development of the adult epithelium. Here we mill review in detail the potential roles for these secreted factors as well as the proposed molecular mechanisms responsible for their physiological functions, Furthermore, me will examine the effect of these proteins on the extracellular environment and how this impacts upon cellular processes involved in intestinal remodeling. C1 NICHHD,MOL EMBRYOL LAB,NIH,BETHESDA,MD 20892. DOKKYO UNIV,SCH MED,DEPT ANAT,MIBU,TOCHIGI 32102,JAPAN. NR 58 TC 9 Z9 9 U1 0 U2 1 PU AMER SOC ZOOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0003-1569 J9 AM ZOOL JI Am. Zool. PD APR PY 1997 VL 37 IS 2 BP 195 EP 207 PG 13 WC Zoology SC Zoology GA WY611 UT WOS:A1997WY61100008 ER PT J AU Duewer, DL Thomas, JB Kline, MC MacCrehan, WA Schaffer, R Sharpless, KE May, WE Crowell, JA AF Duewer, DL Thomas, JB Kline, MC MacCrehan, WA Schaffer, R Sharpless, KE May, WE Crowell, JA TI NIST/NCI micronutrients measurement quality assurance program: Measurement repeatabilities and reproducibilities for fat-soluble vitamin-related compounds in human sera SO ANALYTICAL CHEMISTRY LA English DT Article ID LIQUID-CHROMATOGRAPHIC SEPARATION; BETA-CAROTENE; ELECTROCHEMICAL DETECTION; ALPHA-TOCOPHEROL; RETINOL; ISOMERS AB The NIST/NCI Micronutrient Measurement Quality Assurance Program has conducted 33 interlaboratory comparison exercises for fat-soluble vitamin-related compounds in human sera over the past 12 years, Periodic reanalysis of lyophilized serum samples prepared from more than 70 different sera has enabled estimation of the short- and long-term measurement characteristics. Median- and interquartile-range-based statistics adequately estimate the distribution of results from laboratories that are in analytical control from total distributions that include a significant minority of outlier data, Short-term interlaboratory reproducibility standard deviations (SDs) are predictable functions of analyte concentration, with an asymptotic limit at low analyte concentration and a linear relationship at high concentrations, Long-term trends in the interlaboratory reproducibility can be estimated by standardizing the short-term SD at the observed analyte concentration to an expected SD at a given physiologically significant analyte concentration. The ''average'' laboratory's same-day analytical repeatability SD is about one-third of the estimated interlaboratory reproducibility; repeatability for longer periods between analyses is, on average, no better than the reproducibility. While a few exceptional laboratories have maintained excellent repeatability over the entire decade, long-term study measurements generated within a single laboratory are not generally more internally consistent than results from multiple laboratories, Enhanced and more consistently implemented intralaboratory quality control and quality assurance methods are required to further improve and maintain interlaboratory measurement comparability. C1 NCI,CHEMOPREVENT BRANCH,DIV CANC PREVENT & CONTROL,NIH,BETHESDA,MD 20892. RP Duewer, DL (reprint author), NATL INST STAND & TECHNOL,DIV ANALYT CHEM,CHEM SCI & TECHNOL LAB,GAITHERSBURG,MD 20899, USA. RI Duewer, David/B-7410-2008 NR 25 TC 19 Z9 19 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD APR 1 PY 1997 VL 69 IS 7 BP 1406 EP 1413 DI 10.1021/ac9607727 PG 8 WC Chemistry, Analytical SC Chemistry GA WQ777 UT WOS:A1997WQ77700028 PM 9105181 ER PT J AU Morrow, C Cowan, KH AF Morrow, C Cowan, KH TI Drug resistance markers: Are they bad or good? SO ANNALS OF ONCOLOGY LA English DT Editorial Material ID GLUTATHIONE S-TRANSFERASES; BREAST-CANCER-CELLS; EXPRESSION; SENSITIVITY; PI; GENE; MU C1 NCI,MED BRANCH,BETHESDA,MD 20892. RP Morrow, C (reprint author), WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT BIOCHEM,WINSTON SALEM,NC 27103, USA. NR 18 TC 0 Z9 0 U1 0 U2 1 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 APR PY 1997 VL 8 IS 4 BP 314 EP 315 PG 2 WC Oncology SC Oncology GA XG891 UT WOS:A1997XG89100010 PM 9209659 ER PT J AU Pass, HI Kranda, K Temeck, BK Feuerstein, I Steinberg, SM AF Pass, HI Kranda, K Temeck, BK Feuerstein, I Steinberg, SM TI Surgically debulked malignant pleural mesothelioma: Results and prognostic factors SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 49th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 21-25, 1996 CL ATLANTA, GA SP Soc Surg Oncol DE mesothelioma; surgery; prognostic factors; debulking ID THERAPY; TRIAL AB Background: We analyzed morbidity and mortality, sites of recurrence, and possible prognostic factors in 95 (78 male, 17 female) patients with MPM on phase I-III trials since 1990. A debulking resection to a requisite, residual tumor thickness of less than or equal to 5 mm was required for inclusion. Methods: Preoperative tumor volumes were determined by three-dimensional reconstruction of chest computerized tomograms. Pleurectomy (n = 39) or extrapleural pneumonectomy (EPP; n = 39) was performed. Seventeen patients could not be debulked. Preoperative EPP platelet counts (404,000) and mean tumor volume (491 cm(3)) were greater than that seen for pleurectomy (344,000, 114 cm(3)). Results: Median survival for all patients was 11.2 months, with that for pleurectomy 14.5 months, that for EPP 9.4 months, and that for unresectable patients 5.0 months. Arrhythmia (n = 14; 15%) was the most common complication, and there were two deaths related to surgery (2.0%). Tumor volume of >100 ml, biphasic histology, male sex, and elevated platelet count were associated with decreased survival (p < 0.05). Both EPP and pleurectomy had equivalent recurrence rates (27 of 39 [69%] and 31 of 39 [79%], respectively); however, 17 of 27 EPP recurrences as opposed to 28 of 31 pleurectomy recurrences were locoregional (p(2) = 0.013). Conclusions: Debulking resections for MPM can be performed with low operative mortality. Size and platelet count are important preoperative prognostic parameters for MPM. Patients with poor prognostic indicators should probably enter nonsurgical, innovative trials where toxicity or response to therapy can be evaluated. C1 NIH,DEPT RADIOL,CTR CLIN,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,NIH,BETHESDA,MD 20892. RP Pass, HI (reprint author), NCI,THORAC ONCOL SECT,SURG BRANCH,NIH,BLDG 10,ROOM 2B07,BETHESDA,MD 20892, USA. NR 12 TC 97 Z9 101 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR-MAY PY 1997 VL 4 IS 3 BP 215 EP 222 DI 10.1007/BF02306613 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA WV847 UT WOS:A1997WV84700005 PM 9142382 ER PT J AU Buckheit, RW Snow, MJ FliakasBoltz, V Kinjerski, TL Russell, JD Pallansch, LA Brouwer, WG Yang, SS AF Buckheit, RW Snow, MJ FliakasBoltz, V Kinjerski, TL Russell, JD Pallansch, LA Brouwer, WG Yang, SS TI Highly potent oxathiin carboxanilide derivatives with efficacy against nonnucleoside reverse transcriptase inhibitor-resistant human immunodeficiency virus isolates SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HIV-1 REPLICATION; TIBO DERIVATIVES; BINDING-SITE; NEVIRAPINE; DRUG; INVITRO; SERIES; ENZYME AB The structure-activity relationships of a series of compounds related to the nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) oxathiin carboxanilide have been described (R. W. Buckheit, Jr., T. L. Kinjerski, V. Fliakas-Boltz, J. D. Russell, T. L. Stup, L. A. Pallansch, W. G. Brouwer, D. C. Dao, W. A. Harrison, R. J. Schultz, J. P. Bader, and S. S. Yang, Antimicrob, Agents Chemother, 39:2718-2727, 1996). From these studies, the furanyl-containing analog UC10 was identified as the most potent inhibitor of human immunodeficiency virus type 1 (HIV-1) replication and a promising candidate for further development. Three new UC analogs (UC040, UC82, and UC781) have been determined to inhibit laboratory-derived and low-passage-number, primary virus isolates at low nanomolar concentrations in both established and fresh human cells. Each of the compounds synergistically interacted with the nucleoside analogs zidovudine, dideoxyinosine, dideoxycytosine, and lamivudine to inhibit HIV-1 replication. As a group, the UC compounds were found to be less active against viruses with the L100I, K103N, and Y181C amino acid changes in the RT and, upon in vitro selection, yielded resistant virus with the Y181C mutation in the RT. The most potent of the three new compounds, UC781, contains a furanyl side chain, similar to UC10, but differs in having an extended ether side chain instead of an oxime chain. The broad therapeutic index of UC781 (>62,000) resulted in effective inhibition of NNRTI-resistant virus isolates at high nanomolar concentrations. Furthermore, UC781 and the NNRTI costatolide were able to synergistically inhibit HIV-1 replication when used in combination, suggesting that UC781 may interact with the RT differently than the other UC analogs. The favorable anti-HIV properties of the UC compounds suggest they should be considered for further clinical development. C1 FREDERICK RES CTR,SO RES INST,VIROL RES GRP,FREDERICK,MD 21701. UNIROYAL CHEM LTD,RES LABS,GUELPH,ON,CANADA. NCI,DIV CANC TREATMENT DIAGNOSIS & CTR,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. FU NCI NIH HHS [N01 CM-37818] NR 30 TC 37 Z9 38 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD APR PY 1997 VL 41 IS 4 BP 831 EP 837 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA WR166 UT WOS:A1997WR16600023 PM 9087499 ER PT J AU Brinkmann, U Mansfield, E Pastan, I AF Brinkmann, U Mansfield, E Pastan, I TI Effects of BCL-2 overexpression on the sensitivity of MCF-7 breast cancer cells to ricin, diphtheria and Pseudomonas toxin and immunotoxins SO APOPTOSIS LA English DT Article DE apoptosis; cancer therapy; drug resistance; LMB-7 ID SINGLE-CHAIN IMMUNOTOXINS; DNA FRAGMENTATION; APOPTOSIS; EXPRESSION; CYTOLYSIS; LYMPHOMA; CLONING; LYSIS; GENE; MICE AB Immunotoxins are presently being evaluated as novel agents for cancer therapy. The direct mechanism by which immunotoxins kill cancer cells is inhibition of protein synthesis, but cytotoxicity due to induction of apoptosis has also been observed with these agents. Some cancers that express high levels of BCL-2 are relatively resistant to apoptosis inducing agents. It is therefore important to determine to what degree the toxicity of ricin, diphtheria toxin, Pseudomonas exotoxin and Pseudomonas exotoxin derived immunotoxins towards cancer cells can be attributed to inhibition of protein synthesis, and to what degree to subsequent induction of apoptosis. We compared the sensitivity of MCF-7 breast cancer cells that were stably transfected with a BCL-2 expression plasmid and thus protected against apoptosis and of MCF-7 cells transfected with a control plasmid towards ricin, diphtheria and Pseudomonas toxin, a Pseudomonas toxin-derived immunotoxin (LMB-7) and tumour necrosis factor alpha (TNF). We found that BCL-2 mediated inhibition of apoptosis renders the cells almost completely resistant (1000-fold) to tumour necrosis factor, but the same cells were only 3-10 fold more resistant to cytotoxicity induced by immunotoxin LMB-7 as well as Pseudomonas exotoxin, diphtheria toxin and ricin. We next studied several leukaemia cell lines with variable levels of BCL-5 expression and found them quite sensitive to a Pseudomonas exotoxin containing immunotoxin independent of the level of BCL-2. Our data indicate that although BCL-2 overexpression can have a modest effect on sensitivity to an immunotoxin, cell lines derived from patients are still very sensitive to immunotoxins. C1 NCI,MOL BIOL LAB,NIH,BETHESDA,MD 20892. NR 22 TC 15 Z9 15 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 1360-8185 J9 APOPTOSIS JI Apoptosis PD APR PY 1997 VL 2 IS 2 BP 192 EP 198 DI 10.1023/A:1026468532413 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YD290 UT WOS:A1997YD29000008 PM 14646554 ER PT J AU Huang, Y Chan, AML Liu, Y Wang, X Holbrook, NJ AF Huang, Y Chan, AML Liu, Y Wang, X Holbrook, NJ TI Serum withdrawal and etoposide induce apoptosis in human lung carcinoma cell line A549 via distinct pathways SO APOPTOSIS LA English DT Article DE apoptosis; ERK; JNK; p53; Rb ID CYCLE CHECKPOINT PATHWAY; GROWTH ARREST; ANTICANCER AGENTS; PROTEIN; DEATH; P53; KINASES; BCL-2 AB The molecular events associated with apoptosis induced by two distinct triggers (1) serum withdrawal and (2) etoposide treatment were investigated in the human lung carcinoma cell line A549, Although both serum withdrawal and etoposide treatment resulted in internucleosomal DNA fragmentation, the morphologic features were distinct, Serum deprived apoptotic cells appeared small, round and refractile, with little evidence of nuclear fragmentation; etoposide-induced apoptotic cells appeared enlarged and flattened and displayed prominent nuclear fragmentation, p53 and p21/waf1 protein levels were elevated in etoposide-treated cells, but not in cells subjected to serum withdrawal, Apoptosis induced by both treatments was accompanied by a significant reduction in Rb protein levels. However, etoposide treatment led to hypophosphorylation of Rb, while serum withdrawal did not alter the Rb phosphorylation pattern, Serum withdrawal-induced apoptosis was correlated with activation of JNK and suppression of ERK activities, while both JNK and ERK activities were slightly elevated during etoposid-induced apoptosis, Together, these results support the hypothesis that apoptosis induced by serum withdrawal and etoposide treatment occurs through different pathways and involves distinct mediators. C1 NIA,GENE EXPRESS & AGING SECT,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. MT SINAI MED CTR,DERALD H RUTTENBERG CANC CTR,NEW YORK,NY 10029. RI Liu, Yusen/E-3527-2011 NR 30 TC 15 Z9 16 U1 1 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 1360-8185 J9 APOPTOSIS JI Apoptosis PD APR PY 1997 VL 2 IS 2 BP 199 EP 206 DI 10.1023/A:1026420616484 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YD290 UT WOS:A1997YD29000009 PM 14646555 ER PT J AU Lewis, EN Kidder, LH Arens, JF Peck, MC Levin, IW AF Lewis, EN Kidder, LH Arens, JF Peck, MC Levin, IW TI Si:As focal-plane array detection for Fourier transform spectroscopic imaging in the infrared fingerprint region SO APPLIED SPECTROSCOPY LA English DT Article; Proceedings Paper CT 2nd International Symposium on Advanced Infrared Spectroscopy, AIRS II CY JUN, 1996 CL DUKE UNIV, DURHAM, NC SP Bio Rad Digilab Div, Bruker Spectrospin, Bruker Optics Div, Nicolet Instruments, Duke Univ, Coblenz Soc HO DUKE UNIV DE chemical imaging; infrared microscopy; infrared focal-plane arrays; vibrational spectroscopic imaging; Fourier transform infrared spectroscopy; step-scan interferometry ID RAMAN MICROSCOPY; FLUORESCENCE; ASTRONOMY AB An instrument is described that simultaneously records images and spectra of materials in the infrared fingerprint region using a long-wavelength infrared focal-plane array detector, a step-scan Michelson interferometer, and an infrared microscope. With the combination of step-scan Fourier transform (FT) Michelson interferometry and arsenic-doped silicon (Si:As) focal-plane array image detection, an infrared spectroscopic imaging system has been constructed that maintains both an instrumental multiplex: and multichannel advantage and operates from approximately 4000 to 400 cm(-1). With this method of mid-infrared spectroscopic imaging, the fidelity of the generated spectral images recorded through the microscope is solely determined by the number of pixels on the focal-plane array detector, and only a few seconds of data acquisition time are required for spectral image acquisition, This seamless combination of spectroscopy for molecular analysis and the power of visualization represents the future of infrared microscopy. Step-scan imaging principles, the operation and characteristics of long-wavelength array detectors, and instrument design details are outlined, and infrared chemical imaging results are presented. The results are discussed with respect to their implications for the chemical analysis of a variety of solid-state materials. C1 UNIV CALIF BERKELEY,SPACE SCI LAB,BERKELEY,CA 94720. BERKELEY CAMERA ENGN,HAYWARD,CA 94541. RP Lewis, EN (reprint author), NIDDKD,PHYS CHEM LAB,NIH,BETHESDA,MD 20892, USA. NR 27 TC 31 Z9 31 U1 0 U2 5 PU SOC APPLIED SPECTROSCOPY PI FREDERICK PA 201B BROADWAY ST, FREDERICK, MD 21701 SN 0003-7028 J9 APPL SPECTROSC JI Appl. Spectrosc. PD APR PY 1997 VL 51 IS 4 BP 563 EP 567 DI 10.1366/0003702971940602 PG 5 WC Instruments & Instrumentation; Spectroscopy SC Instruments & Instrumentation; Spectroscopy GA WX756 UT WOS:A1997WX75600021 ER PT J AU Kraemer, HC Kazdin, AE Offord, DR Kessler, RC Jensen, PS Kupfer, DJ AF Kraemer, HC Kazdin, AE Offord, DR Kessler, RC Jensen, PS Kupfer, DJ TI Coming to terms with the terms of risk SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID PSYCHIATRIC-DISORDERS AB Terms such as risk, risk factors, and especially the term cause are inconsistently and imprecisely used, fostering scientific miscommunication and misleading research and policy. Clarifying such terms is the essential first step. We define risk and a risk factor (protective factor) and their potency, set out the conceptual basis of the methods by which risk factors are identified and potency demonstrated, and propose criteria for establishing the status of a risk factor as a fixed or variable marker or a causal risk factor. All definitions are based on the stale of scientific knowledge (empirical documentation), rather than on hypotheses, speculations, or beliefs. We discuss common approaches and pitfalls and give a psychiatric research example. Imprecise reports can impede the search for understanding the cause and course of any disease and also may be a basis of inadequate clinical or policy decision-making. The issues in risk research are much too important to tolerate less than precise terminology or the less than rigorous research reporting that results from imprecise and inconsistent terminology. C1 WESTERN PSYCHIAT INST & CLIN,PITTSBURGH,PA 15213. STANFORD UNIV,DEPT PSYCHIAT & BEHAV SCI,STANFORD,CA 94305. YALE UNIV,DEPT PSYCHOL,NEW HAVEN,CT 06520. MCMASTER UNIV,CHEDOKE MCMASTER HOSP,HAMILTON,ON,CANADA. MCMASTER UNIV,FAC HLTH SCI,HAMILTON,ON,CANADA. HARVARD UNIV,SCH MED,DEPT HLTH CARE POLICY,BOSTON,MA 02115. NIMH,CHILD & ADOLESCENT DISORDERS RES BRANCH,ROCKVILLE,MD 20857. UNIV PITTSBURGH,SCH MED,DEPT PSYCHIAT,PITTSBURGH,PA 15260. OI Jensen, Peter/0000-0003-2387-0650 FU NHLBI NIH HHS [SR01HL39770]; NICHD NIH HHS [R01HD24240]; NIMH NIH HHS [MH00353] NR 20 TC 602 Z9 606 U1 1 U2 55 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 APR PY 1997 VL 54 IS 4 BP 337 EP 343 PG 7 WC Psychiatry SC Psychiatry GA WT581 UT WOS:A1997WT58100006 PM 9107150 ER PT J AU Schwartz, PJ Murphy, DL Wehr, TA GarciaBorreguero, D Oren, DA Moul, DE Ozaki, N Snelbaker, AJ Rosenthal, NE AF Schwartz, PJ Murphy, DL Wehr, TA GarciaBorreguero, D Oren, DA Moul, DE Ozaki, N Snelbaker, AJ Rosenthal, NE TI Effects of meta-chlorophenylpiperazine infusions in patients with seasonal affective disorder and healthy control subjects - Diurnal responses and nocturnal regulatory mechanisms SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; HOODED RAT STRAIN; SEROTONIN AGONIST; BODY-TEMPERATURE; LIGHT THERAPY; NEURO-ENDOCRINE; BEHAVIORAL-RESPONSES; CIRCADIAN PHASE; M-CPP; DEPRESSION AB Background: Multiple lines of evidence suggest that brain serotonergic systems may be disturbed in seasonal affective disorder (SAD). Previously, we found that the serotonergic agent meta-chlorophenylpiperazine (m-CPP) produced increases in activation and euphoria in depressed patients with SAD, but not in patients with SAD following light treatment or in the summer, nor in healthy control subjects in any condition. In the present study, we attempted to replicate and extend this finding using better methods. Methods: Seventeen outpatients with SAD and 15 control subjects underwent successive 3-week periods of bright light treatment and light avoidance in a randomized order. During the third week of each condition, on 2 different occasions, subjects were admitted to the hospital for a night of sleep (core temperatures were recorded), followed by infusions of m-CPP (0.08 mg/kg) or placebo the next morning. Dependent measures included the 24-item National Institute of Mental Health Self-Rating Scale, plasma corticotropin, cortisol, prolactin, growth hormone, and norepinephrine concentrations, and core temperatures. Results: Meta-chlorophenylpiperazine produced (1) significant increases in ''activation-euphoria'' ratings only in depressed patients with SAD in the untreated condition and (2) blunted corticotropin and norepinephrine responses in patients with SAD compared with controls across both light treatment conditions. In both groups, light treatment was associated with significant reductions in nocturnal core temperatures, which were correlated with similarly significant reductions in mean diurnal growth hormone concentrations. In patients with SAD, (1) the reductions in nocturnal core temperatures also were correlated with the reductions in baseline depression ratings and (2) the reductions in mean growth hormone concentrations were significantly smaller compared with controls. Conclusions: The abnormal m-CPP-induced activation-euphoria responses represent a replicated state marker of winter depression in patients with SAD. The blunted m-CPP-induced responsiveness of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system may represent traitlike abnormalities. The improvements in mood following light treatment in patients with SAD seem to be associated with the lowering of nocturnal core temperatures. The findings, although not easily explained based on a uniform abnormality of serotonin receptors, are nonetheless compatible with the notion that selected regions of the central nervous system are deficient in serotonin transmission during winter depression. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NIMH,EPIDEMIOL & PSYCHOPATHOL RES BRANCH,ROCKVILLE,MD 20857. RP Schwartz, PJ (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,BLDG 10,ROOM 4S-239,10 CTR DR,MSC 1390,BETHESDA,MD 20892, USA. RI Ozaki, Norio/M-8908-2014 OI Ozaki, Norio/0000-0002-7360-4898 NR 84 TC 60 Z9 60 U1 1 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 APR PY 1997 VL 54 IS 4 BP 375 EP 385 PG 11 WC Psychiatry SC Psychiatry GA WT581 UT WOS:A1997WT58100010 PM 9107154 ER PT J AU Whitcup, SM Nussenblatt, RB AF Whitcup, SM Nussenblatt, RB TI Immunologic mechanisms of uveitis - New targets for immunomodulation SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE UVEITIS; ENDOTOXIN-INDUCED UVEITIS; CELL-ADHESION MOLECULES; LYMPHOCYTE-T SUBSETS; SYMPATHETIC OPHTHALMIA; ORAL TOLERANCE; LEWIS RATS; MONOCLONAL-ANTIBODIES; BEHCETS-DISEASE; II COLLAGEN AB The uvea consists of the choroid, ciliary body, and iris, and inflammation of the uveal tract is termed uveitis. Nevertheless, uveitis is commonly used to more generally describe intraocular inflammation involving not only the uvea, but also the retina, vitreous, and sclera. Fifty years ago, infectious organisms such as syphilis and tuberculosis were thought to be the cause of most forms of uveitis.(1) Since that time, many causes of uveitis have been described as infectious and noninfectious. Scientists have shown that the immune response plays a critical role in the development of infectious and noninfectious forms of the disease. With a more detailed understanding of the immune mechanisms leading to the development of uveitis, we are now able to develop new therapeutic approaches based on targeting various components of the immune response. RP Whitcup, SM (reprint author), NEI,NATL INST HLTH,10 CTR DR,BLDG 10,ROOM 10N 202,BETHESDA,MD 20892, USA. NR 49 TC 24 Z9 27 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD APR PY 1997 VL 115 IS 4 BP 520 EP 525 PG 6 WC Ophthalmology SC Ophthalmology GA WT596 UT WOS:A1997WT59600012 PM 9109763 ER PT J AU Burchfiel, CM Tracy, RE Chyou, PH Strong, JP AF Burchfiel, CM Tracy, RE Chyou, PH Strong, JP TI Cardiovascular risk factors and hyalinization of renal arterioles at autopsy - The Honolulu Heart Program SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE Asian Americans; diabetes mellitus; atherosclerosis; hyaline substance; nephrosclerosis ID HIGH-DENSITY-LIPOPROTEIN; CORONARY-ARTERY DISEASE; BLOOD-PRESSURE; JAPANESE MEN; ALCOHOL-CONSUMPTION; LIFESTYLE CHARACTERISTICS; MYOCARDIAL LESIONS; ATHEROSCLEROSIS; NEPHROSCLEROSIS; HAWAII AB Nephrosclerosis, commonly found in subjects with hypertension and diabetes, is marked by hyalinization of arterioles and fibroplasia of small arteries in the renal cortex. Cardiovascular risk factors that predicted subsequent hyalinization of renal arterioles at autopsy were identified, using data from the Honolulu Heart Program, a prospective epidemiological study of cardiovascular disease (CVD) in Japanese-American men. Among 8006 participants at baseline, 1381 died between 1965 and 1982; 285 of these had a protocol autopsy, and 150 had assessments of arteriolar hyalinization from renal tissue. Subjects were categorized into four groups on the basis of the number of hyalinized arterioles per square centimeter of renal tissue, and CVD risk factor levels and proportions were compared across these groups with the use of general linear models and logistic regression. Multivariate assessment using logistic regression demonstrated that diastolic blood pressure (DBP) and glucose level were positively associated and alcohol intake was negatively associated with an elevated degree of renal arteriolar hyalinization, independent of other CVD risk factors. The odds ratios for elevated hyalinization associated with a 10-mm Hg increase in DBP, a 20-mg/dL increase in glucose level, and a 30-mL/d increase in alcohol intake were 1.97 (95% confidence interval [CI]=1.24-3.12), 1.23 (95% CI=1.07-1.41), and 0.24 (95% CI=0.11-0.55), respectively. Associations were similar when prevalent cases of CVD were excluded and when autopsy selection bias was taken into account. Renal arteriolar hyalinization was also more strongly associated with atherosclerosis in the larger cerebral vessels (Spearman's r=.59, P<.001) than in the coronary arteries (r=.16, P=.073) and aorta (r=.24, P=.022). Hyalinization was significantly related to cardiovascular-renal mortality, and this association was accounted for by other CVD risk factors. These findings suggest that blood pressure, glucose level, and alcohol intake are independent predictors of hyalinization in renal arterioles and that this type of renal vasculopathy may be a marker for atherosclerosis in other vascular regions, particularly the cerebral vessels. The protective association involving alcohol and the possibility that renal arteriolar hyalinization may be an indicator of cerebral atherosclerosis may warrant investigation in other populations. C1 NHLBI,HONOLULU EPIDEMIOL RES UNIT,EPIDEMIOL & BIOMETRY PROGRAM,DIV EPIDEMIOL & CLIN APPLICAT,HONOLULU,HI. LOUISIANA STATE UNIV,MED CTR,DEPT PATHOL,NEW ORLEANS,LA 70112. RP Burchfiel, CM (reprint author), KUAKINI MED CTR,HONOLULU HEART PROGRAM,THOMAS SQ CTR,846 S HOTEL ST,SUITE 306,HONOLULU,HI 96813, USA. FU NHLBI NIH HHS [N01-HC-02901, N01-HC-05102] NR 59 TC 45 Z9 45 U1 0 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD APR PY 1997 VL 17 IS 4 BP 760 EP 768 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA WU591 UT WOS:A1997WU59100021 PM 9108792 ER PT J AU Felson, DT Zhang, YQ Hannan, MT Naimark, A Weissman, B Aliabadi, P Levy, D AF Felson, DT Zhang, YQ Hannan, MT Naimark, A Weissman, B Aliabadi, P Levy, D TI Risk factors for incident radiographic knee osteoarthritis in the elderly - The Framingham Study SO ARTHRITIS AND RHEUMATISM LA English DT Article ID OSTEO-ARTHRITIS; PHYSICAL-ACTIVITY; HIP; ASSOCIATION; SMOKING; WEIGHT; HEALTH; WOMEN; CHONDROCALCINOSIS; PREVALENCE AB Objective. Knee osteoarthritis (OA) is highly prevalent, especially in the elderly, Preventive strategies require a knowledge of risk factors that precede disease onset, The present study was conducted to determine the longitudinal risk factors for knee OA in an elderly population. Methods. A longitudinal study of knee OA involving members of the Framingham Study cohort was performed, Weight-bearing knee radiographs were obtained in 1983-1985 (baseline) and again in 1992-1993, Incident disease was defined as the occurrence of new radiographic OA (Kellgren and Lawrence grade greater than or equal to 2 on a 0-4 scale) in those without radiographic OA at baseline. Risk factors assessed at baseline and in the interim were tested in univariate and multivariate equations to evaluate their association with incident knee OA. Results. Of 598 patients without knee OA at baseline (mean age 70.5 years, 63.7% women), 93 (15.6%) developed OA, After adjustment for multiple risk factors, women had a higher risk of OA than did men (adjusted odds ratio [OR] = 1.8, 95% confidence interval [95% CI] 1.1-3.1), Higher baseline body mass index increased the risk of OA (OR = 1.6 per 5-unit increase, 95% CI 1.2-2.2), and weight change was directly correlated with the risk of OA (OR = 1.4 per 10-lb change in weight, 95% CI 1.1-1.8), Physical activity increased the risk of OA (for those in the highest quartile, OR = 3.3, 95% CI 1.4-7.5), Smokers had a lower risk than did nonsmokers (for those who smoked an average of greater than or equal to 10 cigarettes/day, OR = 0.4, 95% CI 0.2-0.8), Factors not associated with the risk of OA included chondrocalcinosis and a history of hand OA, Weight-related factors affected the risk of OA only in women. Conclusion. Elderly persons at high risk of developing radiographic knee OA included obese persons, nonsmokers, and those who were physically active. The direction of weight change correlated directly with the risk of developing OA. C1 BOSTON UNIV,MED CTR,ARTHRIT CTR,BOSTON,MA. BOSTON CITY HOSP,BOSTON,MA 02118. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. NHLBI,BETHESDA,MD 20892. FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA. OI Hannan, Marian/0000-0002-9586-6928 FU NIA NIH HHS [AG-09300]; NIAMS NIH HHS [AR-20613] NR 32 TC 405 Z9 422 U1 3 U2 13 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD APR PY 1997 VL 40 IS 4 BP 728 EP 733 DI 10.1002/art.1780400420 PG 6 WC Rheumatology SC Rheumatology GA WR366 UT WOS:A1997WR36600019 PM 9125257 ER PT J AU Mellemkjaer, L Andersen, V Linet, MS Gridley, G Hoover, R Olsen, JH AF Mellemkjaer, L Andersen, V Linet, MS Gridley, G Hoover, R Olsen, JH TI Non-Hodgkin's lymphoma and other cancers among a cohort of patients with systemic lupus erythematosus SO ARTHRITIS AND RHEUMATISM LA English DT Article ID RHEUMATOID-ARTHRITIS; INCREASED RISK; ASSOCIATION; MALIGNANCY; CLASSIFICATION; NEOPLASIA; CRITERIA; ETIOLOGY; DISEASES; SURVIVAL AB Objective. To investigate whether systemic lupus erythematosus (SLE) is associated with non-Hodgkin's lymphoma or other malignant neoplasms. Methods. Data on a cohort of 1,585 patients with SLE from the nationwide Danish Hospital Discharge Register were linked to information in the Danish Cancer Registry to determine the occurrence of cancer during up to 15 years of followup, The expected number of cancers was calculated from accumulated person-years and national cancer incidence rates. Results. There was a significant excess of non-Hodgkin's lymphoma among the SLE patients, based on 8 cases observed against 1.5 expected (relative risk [RR] 5.2, 95% confidence interval 2.2-10.3), In addition, a significantly increased RR was found for cancer of the lung (RR 1.9; n = 15), the liver (RR 8.0; n = 5), and the vagina/vulva (RR 5.7; n = 3). Conclusion. There seemed to be a positive association between SLE and non-Hodgkin's lymphoma, Other cancers with a possible virus-related etiology, such as liver and vaginal/vulva cancer, were also observed in excess, In addition, there was an indication of an increased risk of lung cancer among patients who were hospitalized for SLE. C1 NATL UNIV HOSP,COPENHAGEN,DENMARK. NATL CANC INST,BETHESDA,MD. RP Mellemkjaer, L (reprint author), DANISH CANC SOC,DIV CANC EPIDEMIOL,STRANDBLVD 49,DK-2100 COPENHAGEN O,DENMARK. NR 48 TC 160 Z9 165 U1 0 U2 6 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD APR PY 1997 VL 40 IS 4 BP 761 EP 768 DI 10.1002/art.1780400424 PG 8 WC Rheumatology SC Rheumatology GA WR366 UT WOS:A1997WR36600023 PM 9125261 ER PT J AU Torrey, EF Miller, J AF Torrey, EF Miller, J TI Season of birth and schizophrenia: Southern hemisphere data SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Letter RP Torrey, EF (reprint author), NIMH,CTR NEUROSCI,WASHINGTON,DC 20032, USA. NR 5 TC 4 Z9 4 U1 1 U2 1 PU BLACKWELL SCIENCE PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON VICTORIA 3053, AUSTRALIA SN 0004-8674 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD APR PY 1997 VL 31 IS 2 BP 308 EP 309 PG 2 WC Psychiatry SC Psychiatry GA XN686 UT WOS:A1997XN68600028 PM 9140645 ER PT J AU Litvan, I AF Litvan, I TI Progressive supranuclear palsy and corticobasal degeneration SO BAILLIERES CLINICAL NEUROLOGY LA English DT Article DE progressive supranuclear palsy; corticobasal degeneration; diagnosis; therapy; atypical parkinsonian disorders ID RICHARDSON-OLSZEWSKI-SYNDROME; POSITRON EMISSION TOMOGRAPHY; BASAL GANGLIONIC DEGENERATION; MULTIPLE SYSTEM ATROPHY; PARKINSONS-DISEASE; STRIATONIGRAL DEGENERATION; FRONTAL-LOBE; PURE AKINESIA; NEUROPSYCHOLOGICAL PATTERN; CLINICAL-CRITERIA AB The clinical and neuropathological features characteristic of progressive supranuclear palsy and corticobasal degeneration are described in detail. These disorders are not as rare as previously believed, but are poorly recognized. In patients with parkinsonism, a high index of clinical suspicion, Sometimes complemented by specific laboratory tests, should improve diagnostic accuracy. Biological treatments are at present not available, but suggested symptomatic therapies may improve the quality of life of patients with these disorders. C1 NINDS, Def & Vet Head Injury Program, Neuropharmacol Unit, Jackson Fdn,NIH, Bethesda, MD 20892 USA. NINDS, Neuroepidemiol Branch, NIH, Bethesda, MD 20892 USA. RP Litvan, I (reprint author), NINDS, Def & Vet Head Injury Program, Neuropharmacol Unit, Jackson Fdn,NIH, Fed Bldg,Room 714, Bethesda, MD 20892 USA. OI Litvan, Irene/0000-0002-3485-3445 NR 93 TC 19 Z9 20 U1 0 U2 1 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0961-0421 J9 BAILLIERE CLIN NEUR JI Baillieres Clin. Neurol. PD APR PY 1997 VL 6 IS 1 BP 167 EP 185 PG 19 WC Clinical Neurology SC Neurosciences & Neurology GA YM542 UT WOS:000071075200011 PM 9426874 ER PT J AU Jucker, M Ingram, DK AF Jucker, M Ingram, DK TI Murine models of brain aging and age-related neurodegenerative diseases SO BEHAVIOURAL BRAIN RESEARCH LA English DT Review DE mouse models; mutant; transgenic; knock-out; senescence accelerated mouse; CNS; Alzheimer's disease; structural changes; neurodegeneration; oxidative stress; selective breeding; lesion ID SENESCENCE-ACCELERATED MOUSE; AMYLOID PRECURSOR PROTEIN; FIBRILLARY ACIDIC PROTEIN; FAMILIAL ALZHEIMERS-DISEASE; ELEVATED CORTICOSTERONE LEVELS; FOREBRAIN CHOLINERGIC NEURONS; ZINC SUPEROXIDE-DISMUTASE; FOCAL CEREBRAL-ISCHEMIA; CENTRAL-NERVOUS-SYSTEM; FEMALE C57BL/6J MICE AB In the past, structural changes in the brain with aging have been studied using a variety of animal models, with rats and nonhuman primates being the most popular. With the rapid evolution of mouse genetics, murine models have gained increased attention in the neurobiology of aging. The genetic contribution of age-related traits as well as specific mechanistic hypotheses underlying brain aging and age-related neurodegenerative diseases can now be assessed by using genetically-selected and genetically-manipulated mice. Against this background of increased demand for aging research in mouse models, relatively few studies have examined structural alterations with aging in the normal mouse brain, and the data available are almost exclusively restricted to the C57BL/6 strain. Moreover, many older studies have used quantitative techniques which today can be questioned regarding their accuracy. Here we review the state of knowledge about structural changes with aging in outbred, inbred, genetically-selected, and genetically-engineered murine models. Moreover, we suggest several new opportunities that are emerging to study brain aging and age-related neurodegenerative diseases using genetically-defined mouse models. By reviewing the literature, it has become clear to us that in light of the rapid progress in genetically-engineered and selected mouse models for brain aging and age-related neurodegenerative diseases, there is a great and urgent need to study and define morphological changes in the aging brain of normal inbred mice and to analyze the structural changes in genetically-engineered mice more carefully and completely than accomplished to date. Such investigations will broaden knowledge in the neurobiology of aging, particularly regarding the genetics of aging, and possibly identify the most useful murine models. C1 UNIV BASEL, INST PATHOL, NEUROPATHOL LAB, CH-4003 BASEL, SWITZERLAND. RP Jucker, M (reprint author), NIA, GERONTOL RES CTR, NATHAN W SHOCK LABS, BALTIMORE, MD 21224 USA. NR 261 TC 63 Z9 68 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD APR PY 1997 VL 85 IS 1 BP 1 EP 25 DI 10.1016/S0166-4328(96)02243-7 PG 25 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA WQ793 UT WOS:A1997WQ79300001 PM 9095338 ER PT J AU Schulte, TW Toretsky, JA Ress, E Helman, L Neckers, LM AF Schulte, TW Toretsky, JA Ress, E Helman, L Neckers, LM TI Expression of PAX3 in Ewing's sarcoma family of tumors SO BIOCHEMICAL AND MOLECULAR MEDICINE LA English DT Article ID ALVEOLAR RHABDOMYOSARCOMA; PROTOONCOGENE EXPRESSION; TRANSCRIPTION FACTORS; WILMS-TUMORS; CELLS; PROTEIN; FUSION; GENES; TRANSLOCATION; CARCINOMA AB The Ewing's sarcoma family of tumors (ESFT) is the second most common pediatric malignancy originating in the bone and is characterized by the t(11; 22) translocation. PAX3, a member of the paired box family of genes, is expressed during embryonal development of neural crest cells and is involved in the t(2; 13) translocation found in alveolar rhabdomyosarcoma. Since ESFTs are believed to be derived from neural crest tissue, we screened a series of Ewing's sarcoma and peripheral neuroectodermal tumor cell lines and tumor specimens for expression of PAX3. We found expression of PAX3 in most, but not all, of the specimens analyzed, including cell lines and patient material. (C) 1997 Academic Press. C1 NCI,PEDIAT BRANCH,NIH,BETHESDA,MD 20892. RP Schulte, TW (reprint author), NCI,CLIN PHARMACOL BRANCH,NIH,BLDG 10,ROOM 13N240,10 CTR DR MSC 1928,BETHESDA,MD 20892, USA. NR 39 TC 18 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 1077-3150 J9 BIOCHEM MOL MED JI Biochem. Mol. Med. PD APR PY 1997 VL 60 IS 2 BP 121 EP 126 DI 10.1006/bmme.1997.2567 PG 6 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA WW752 UT WOS:A1997WW75200006 PM 9169092 ER PT J AU Lohmeyer, M Harrison, PM Kannan, S DeSantis, M OReilly, NJ Sternberg, MJE Salomon, DS Gullick, WJ AF Lohmeyer, M Harrison, PM Kannan, S DeSantis, M OReilly, NJ Sternberg, MJE Salomon, DS Gullick, WJ TI Chemical synthesis, structural modeling, and biological activity of the epidermal growth factor-like domain of human Cripto SO BIOCHEMISTRY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; RECEPTOR-BINDING; CRYSTAL-STRUCTURE; PROTEIN STRUCTURES; HEREGULIN-ALPHA; BETA-HAIRPINS; FACTOR FAMILY; CANCER CELLS; HUMAN BRAIN; FACTOR GENE AB Cripto, also known as human teratocarcinoma-derived growth factor 1 (TDGF-1), contains a 40 amino acid region with some similarity to the epidermal growth factor (EGF) domain. However, sequence homology is largely restricted to the classical cysteine/glycine motif with only limited similarities in other regions. Significant differences to human EGF include the absence of all seven residues between the two N-terminal half-cystines and a five-residue shorter loop between the third and fourth half-cystines. We examine the hypothesis that, in spite of these differences, cripto can adopt the characteristic EGF-like 1-3, 2-4, 5-6 disulfide bond pattern. A comparative structural model of the growth factor cripto was constructed on the basis of its similarity to EGF, transforming growth factor alpha (TGF-alpha), and the EGF-like domain of human clotting factor IX. The predicted disulfide bridges and disulfide-bridged loops were analyzed and appear viable in the modeled structure. Moreover, to ascertain the importance of disulfide arrangement for cripto bioactivity, two 47-residue peptides were synthesized and then refolded using either a simple oxidative or a controlled sequential refolding protocol. The cripto peptides were tested for their ability to stimulate MAP-kinase activity, for inhibition of beta-casein induction, and for Shc phosphorylation in MDA-MB 453 human mammary carcinoma cells and HC-11 mouse mammary epithelial cells. Data suggest that cripto does adopt the 1-3, 2-4, 5-6 disulfide pattern and thus forms the classical EGF-like fold in spite of the significant deletions within the folding domain. The predicted structure of cripto shows some of the characteristics of both the ErbB1- and ErbB3/ErbB4-binding growth factors. C1 HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,IMPERIAL CANC RES FUND,MOL ONCOL LAB,LONDON W12 0NN,ENGLAND. IMPERIAL CANC RES FUND,BIOMOLEC MODELLING LAB,LONDON WC2A 3PX,ENGLAND. NCI,TUMOR GROWTH FACTOR SECT,TUMOR IMMUNOL & BIOL LAB,NIH,BETHESDA,MD 20892. IMPERIAL CANC RES FUND,PEPTIDE SYNTH,LONDON WC2A 3PX,ENGLAND. NR 50 TC 24 Z9 24 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 1 PY 1997 VL 36 IS 13 BP 3837 EP 3845 DI 10.1021/bi961542p PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WR180 UT WOS:A1997WR18000011 PM 9092813 ER PT J AU Szebeni, A Mehrotra, B Baumann, A Adam, SA Wingfield, PT Olson, MOJ AF Szebeni, A Mehrotra, B Baumann, A Adam, SA Wingfield, PT Olson, MOJ TI Nucleolar protein B23 stimulates nuclear import of the HIV-1 Rev protein and NLS-conjugated albumin SO BIOCHEMISTRY LA English DT Article ID LARGE-T-ANTIGEN; LOCALIZATION SIGNALS; PORE COMPLEX; PHOSPHORYLATION SITE; LOCATION SEQUENCE; KINASE-II; IDENTIFICATION; ENVELOPE; BINDING; TRANSPORT AB Nucleolar phosphoprotein B23 is a putative ribosome assembly factor with a relatively high affinity for peptides containing sequences of nuclear localization signals (NLSs) of the SV40 T-antigen type [Szebeni, A., Herrera, J. E., & Olson, O. J. (1995) Biochemistry 34, 8037-8042]. The effects of protein B23 on nuclear import were determined by an in vitro assay [Dean, D. A., & Kasamatsu, H. (1994) J. Biol. Chem. 269, 4910-4916] using NLS peptide-conjugated bovine serum albumin (NLS-BSA) or the HIV-1 Rev protein as substrates for import into isolated rat liver nuclei. The import was ATP-dependent and inhibited by wheat germ agglutinin or by an antibody against p97, a component of the nuclear import system. The rate of import of either substrate was increased if protein B23 was added to the incubation medium. Similar enhancements of import were seen with both isoforms (B23.1 and B23.2). The stimulatory effect on Rev protein import was saturable with maximum stimulation (2-3-fold) at a molar ratio of protein B23:Rev of approximately 1:1. Phosphorylation of protein B23.1 by casein kinase II produced an additional doubling of the import rate. This effect was not seen if protein B23.1 was phosphorylated with a cdc2 type protein kinase. Mutant forms of protein B23.1 in which the nuclear localization signal was either deleted or altered did not stimulate import of the substrates. These results suggest that protein B23 plays a role as an accessory factor in the nuclear import of the NLS-containing proteins and that phosphorylation at sites in the highly acidic segments of the protein enhances the stimulatory effect. C1 UNIV MISSISSIPPI,MED CTR,DEPT BIOCHEM,JACKSON,MS 39216. TOUGALOO COLL,DEPT CHEM,TOUGALOO,MS 39174. NORTHWESTERN UNIV,SCH MED,DEPT CELL & MOL BIOL,CHICAGO,IL 60611. NIH,PROT EXPRESS LAB,BETHESDA,MD 20892. FU NIAID NIH HHS [AI34277]; NIGMS NIH HHS [GM00659, GM28349] NR 55 TC 76 Z9 79 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 1 PY 1997 VL 36 IS 13 BP 3941 EP 3949 DI 10.1021/bi9627931 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WR180 UT WOS:A1997WR18000022 PM 9092824 ER PT J AU Gao, CY Zelenka, PS AF Gao, CY Zelenka, PS TI Cyclins, cyclin-dependent kinases and differentiation SO BIOESSAYS LA English DT Review ID CELL-CYCLE; PROTEIN-KINASE; TERMINAL DIFFERENTIATION; NEURONAL DIFFERENTIATION; HL-60 CELLS; PC12 CELLS; RETINOBLASTOMA PROTEIN; EXPRESSION; COMPLEX; FAMILY AB Cyclin-dependent kinases and their regulatory subunits, the cyclins, are known to regulate progression through the cell cycle. Yet these same proteins are often expressed in non-cycling, differentiated cells. This review surveys the available information about cyclins and cyclin-dependent kinases in differentiated cells and explores the possibility that these proteins may have important functions that are independent of cell cycle regulation. C1 NEI,MOL & DEV BIOL LAB,NIH,BETHESDA,MD 20892. NR 70 TC 99 Z9 107 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0265-9247 J9 BIOESSAYS JI Bioessays PD APR PY 1997 VL 19 IS 4 BP 307 EP 315 DI 10.1002/bies.950190408 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA WU470 UT WOS:A1997WU47000007 PM 9136628 ER PT J AU Distel, DL Roberts, SJ AF Distel, DL Roberts, SJ TI Bacterial endosymbionts in the gills of the deep-sea wood-boring bivalves Xylophaga atlantica and Xylophaga washingtona SO BIOLOGICAL BULLETIN LA English DT Article ID TEREDINIDAE; MORPHOLOGY; SYMBIOSES; GROWTH AB Bacterial endosymbionts found in gill tissues in several bivalve families convert otherwise unavailable energy sources (sulfide, methane, or cellulose) to forms readily metabolized by their hosts. We investigated the existence of such a symbiosis in two species of Xylophaga (family Pholadidae). The genus Xylophaga includes opportunistic species that are the predominant colonizers of wood at depths greater than 150 m. It has been hypothesized that, like their shallow-water counterparts the shipworms (family Teredinidae), species of Xylophaga utilize wood for nutrition. Results from transmission and scanning electron microscopy of X. atlantica and X. washingtona clearly demonstrate the presence of endosymbionts that resemble the shipworm endosymbionts both morphologically and in their anatomical location within the gills, Xylophaga and the teredinids both have a caecum packed with wood chips but lack the dense populations of microorganisms associated with cellulose digestion in termites or ruminants, These observations suggest that Xylophaga has evolved a symbiotic solution to wood digestion similar to that seen in shipworms. Hence, the Xylophaga symbiosis suggests a mechanism for the conversion of terrestrially derived cellulosic carbon from wood into animal biomass in the deep sea. C1 NCI,MB,DCS,NIH,BETHESDA,MD 20892. RP Distel, DL (reprint author), UNIV MAINE,DEPT MOL GENET BIOCHEM & MICROBIOL,ORONO,ME 04469, USA. RI Distel, Daniel/A-8047-2017 OI Distel, Daniel/0000-0002-3860-194X NR 29 TC 57 Z9 57 U1 2 U2 13 PU MARINE BIOLOGICAL LABORATORY PI WOODS HOLE PA 7 MBL ST, WOODS HOLE, MA 02543 SN 0006-3185 J9 BIOL BULL JI Biol. Bull. PD APR PY 1997 VL 192 IS 2 BP 253 EP 261 DI 10.2307/1542719 PG 9 WC Biology; Marine & Freshwater Biology SC Life Sciences & Biomedicine - Other Topics; Marine & Freshwater Biology GA WX539 UT WOS:A1997WX53900006 PM 9145497 ER PT J AU Rothman, RB Ayestas, M Glowa, JR Baumann, MH AF Rothman, RB Ayestas, M Glowa, JR Baumann, MH TI Phentermine reduces cocaine-induced increases in brain DA and cocaine self-administration SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIDA,DIR,CLIN PSYCHOPHARMACOL SECT,NIH,BALTIMORE,MD 21224. LOUISIANA STATE UNIV,MED CTR,DEPT PHARMACOL & EXPT THERAPEUT,SHREVEPORT,LA 71130. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 20 EP 20 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900022 ER PT J AU Callicott, JH Bertolino, A Mattay, VS Santha, AK Finn, K Coppola, R Goldberg, TE Frank, JA Weinberger, DR AF Callicott, JH Bertolino, A Mattay, VS Santha, AK Finn, K Coppola, R Goldberg, TE Frank, JA Weinberger, DR TI fMRI of a parametric working memory task in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,IRP,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NIH,OIR,LAB DIAGNOST RADIOL RES,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 35 EP 35 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900037 ER PT J AU Callicott, JH Santha, AK Mattay, VS vanHorn, JD Podell, D Finn, K Bertolino, A Coppola, R Frank, JA Weinberger, DR AF Callicott, JH Santha, AK Mattay, VS vanHorn, JD Podell, D Finn, K Bertolino, A Coppola, R Frank, JA Weinberger, DR TI Statistical power and the creation of intrasubject activation maps in fMRI SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,IRP,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NIH,OIR,LAB DIAGNOST RADIOL RES,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 36 EP 36 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900038 ER PT J AU Krasuski, JS Alexander, GE Horwitz, B Daly, E Rapoport, SI Schapiro, MB AF Krasuski, JS Alexander, GE Horwitz, B Daly, E Rapoport, SI Schapiro, MB TI Age-related medial temporal lobe volume changes in Down syndrome SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIA,NEUROSCI LAB,NIH,BETHESDA,MD 20852. RI daly, eileen/B-6716-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 52 EP 52 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900054 ER PT J AU Pietrini, P Dani, A Furey, ML Alexander, GE Freo, U Mentis, MJ Schapiro, MB AF Pietrini, P Dani, A Furey, ML Alexander, GE Freo, U Mentis, MJ Schapiro, MB TI Brain metabolism in relation to onset of dementia in down syndrome SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIA,NEUROSCI LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 59 EP 59 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900061 ER PT J AU Pietrini, P Dani, A Furey, ML Alexander, GE Freo, U Mentis, MJ Schapiro, MB AF Pietrini, P Dani, A Furey, ML Alexander, GE Freo, U Mentis, MJ Schapiro, MB TI Baseline cerebral metabolism differs in responders to lamotrigine or gabapentin SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. STANFORD UNIV,SCH MED,STANFORD,CA 94305. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 60 EP 60 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900062 ER PT J AU Kimbrell, TA Ketter, TA Danielson, AL Benson, BE Dunn, RT Little, JL Willis, MW Herscovitch, P Post, RM AF Kimbrell, TA Ketter, TA Danielson, AL Benson, BE Dunn, RT Little, JL Willis, MW Herscovitch, P Post, RM TI Serial resting cerebral blood flow measurement in healthy volunteers SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. STANFORD UNIV,SCH MED,STANFORD,CA 94305. NIH,PET DEPT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 61 EP 61 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900063 ER PT J AU Willis, MW Ketter, TA Kimbrell, TA Danielson, AL Benson, BE Little, JT Post, RM AF Willis, MW Ketter, TA Kimbrell, TA Danielson, AL Benson, BE Little, JT Post, RM TI Differential changes in cerebral metabolism with age in mood disorder subtypes SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,NIH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. STANFORD UNIV,SCH MED,STANFORD,CA 94305. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 62 EP 62 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900064 ER PT J AU Williams, W Ramsey, N Ruttimann, U Kerich, M Rio, D Rawlings, R Linnoila, M Hommer, D AF Williams, W Ramsey, N Ruttimann, U Kerich, M Rio, D Rawlings, R Linnoila, M Hommer, D TI Regional cerebral blood flow changes in response to olfactory stimuli: A comparison of alcoholic patients versus controls by PET SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIAAA,NIH,DICBR,CLIN STUDIES LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 64 EP 64 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900066 ER PT J AU Knox, S UvnasMoberg, K AF Knox, S UvnasMoberg, K TI Social isolation and cardiovascular disease: Mediating mechanisms SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NHLBI,BEHAV MED RES GRP,BETHESDA,MD 20892. KAROLINSKA INST,DEPT PHYSIOL & PHARMACOL,STOCKHOLM,SWEDEN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 81 EP 81 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900083 ER PT J AU Willeit, M PraschakRieder, N Asenbaum, S Neumeister, A Hesselmann, B Habeler, A Ibatoullina, E Tauscher, J Pirker, W Brucke, T Kasper, S AF Willeit, M PraschakRieder, N Asenbaum, S Neumeister, A Hesselmann, B Habeler, A Ibatoullina, E Tauscher, J Pirker, W Brucke, T Kasper, S TI Serotonin transporter density in depressed SAD patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 UNIV VIENNA,DEPT GEN PSYCHIAT,VIENNA,AUSTRIA. UNIV VIENNA,DEPT NEUROL,VIENNA,AUSTRIA. NIMH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 101 EP 101 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900103 ER PT J AU PraschakRieder, N Neumeister, A Hesselmann, B Vitouch, O Habeler, A Willeit, M Kasper, S AF PraschakRieder, N Neumeister, A Hesselmann, B Vitouch, O Habeler, A Willeit, M Kasper, S TI Serotonergic mechanisms in SAD patients during stable remission in summer SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. UNIV VIENNA,DEPT PSYCHIAT,A-1010 VIENNA,AUSTRIA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 102 EP 102 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900104 ER PT J AU Frye, MA Kimbrell, TA Willis, MW Ketter, TA George, MS Pazzaglia, PJ Dunn, RT Luckenbaugh, D Huggins, T Little, JT Vanderham, L Danielson, A Benson, B Davis, C Rubinow, DR Post, RM AF Frye, MA Kimbrell, TA Willis, MW Ketter, TA George, MS Pazzaglia, PJ Dunn, RT Luckenbaugh, D Huggins, T Little, JT Vanderham, L Danielson, A Benson, B Davis, C Rubinow, DR Post, RM TI Low CSF somatostatin and cerebral hypometabolism in depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD. STANFORD UNIV,STANFORD,CA 94305. MED UNIV S CAROLINA,CHARLESTON,SC 29425. UNIV MISSISSIPPI,SCH MED,JACKSON,MS 39216. NIMH,BEHAV ENDOCRINOL BRANCH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 111 EP 111 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900113 ER PT J AU Frye, MA Pazzaglia, PJ Luckenbaugh, D Kimbrell, TA Little, JT Dunn, RT George, MS Huggins, T Vanderham, L Leverich, GS Davis, C Rubinow, DR Post, RM AF Frye, MA Pazzaglia, PJ Luckenbaugh, D Kimbrell, TA Little, JT Dunn, RT George, MS Huggins, T Vanderham, L Leverich, GS Davis, C Rubinow, DR Post, RM TI Baseline CSF somatostatin predictive of nimodipine treatment response SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. UNIV MISSISSIPPI,SCH MED,JACKSON,MI. MED UNIV S CAROLINA,BEHAV ENDOCRINOL BRANCH,CHARLESTON,SC 29425. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 112 EP 112 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900114 ER PT J AU Bloch, M Schmidt, PJ Rubinow, DR AF Bloch, M Schmidt, PJ Rubinow, DR TI An endocrine model for postpartum mood disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,BEHAV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 119 EP 119 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900121 ER PT J AU Bachus, SE Hyde, TM Herman, MM Kleinman, JE AF Bachus, SE Hyde, TM Herman, MM Kleinman, JE TI Reduced postmortem hippocampal cholecystokinin MRNA in schizophrenics and neuroleptic-treated patients with bipolar affective disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,NEUROSCI CTR ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 140 EP 140 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900142 ER PT J AU Stine, OC McMahon, FJ Chen, L Xu, J Meyers, DA MacKinnon, D Simpson, S McInnis, M Rice, JP Goate, A Reich, T Edenberg, H Foroud, T Nurnberger, J DeteraWadleigh, S Goldin, L Guroff, J Gershon, ES Blehar, M DePaulo, JR AF Stine, OC McMahon, FJ Chen, L Xu, J Meyers, DA MacKinnon, D Simpson, S McInnis, M Rice, JP Goate, A Reich, T Edenberg, H Foroud, T Nurnberger, J DeteraWadleigh, S Goldin, L Guroff, J Gershon, ES Blehar, M DePaulo, JR TI Initial genome screen for bipolar disorder in NIMH genetics initiative pedigrees: Chromosomes 2, 11, 13, 14, X SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,BALTIMORE,MD. WASHINGTON UNIV,ST LOUIS,MO. INDIANA UNIV,MED CTR,INDIANAPOLIS,IN. NIH,BETHESDA,MD 20892. RI McMahon, Francis/A-7290-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 141 EP 141 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900143 ER PT J AU AlAmin, HA Lipska, BK Weinberger, DR AF AlAmin, HA Lipska, BK Weinberger, DR TI Differential effects of neonatal cortical lesions on the MK-801-induced behaviors in adult rats SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,NEUROSCI CTR ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,IRP,WASHINGTON,DC 20032. RI Lipska, Barbara/E-4569-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 150 EP 150 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900152 ER PT J AU Hamid, EH Altemus, M Hyde, TM Egan, MF AF Hamid, EH Altemus, M Hyde, TM Egan, MF TI Activity-induced changes in striatal neuropeptide gene expression are not exclusive to compulsive running in a rat model of OCD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 CORNELL UNIV,MED CTR,NEW YORK,NY 10021. NIMH,NEUROSCI CTR ST ELIZABETHS,WASHINGTON,DC 20032. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 151 EP 151 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900153 ER PT J AU Kling, MA DeBellis, MD Geracioti, TD ORourke, DK Oldfield, EH Murphy, DL Gold, PW AF Kling, MA DeBellis, MD Geracioti, TD ORourke, DK Oldfield, EH Murphy, DL Gold, PW TI Relationship of ENA and 5-HIAA in normal CSF measured hourly for 30 hours SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,CNE BRANCH,BETHESDA,MD 20892. NIMH,LCS,BETHESDA,MD 20892. VET ADM MED CTR,BALTIMORE,MD 21201. UNIV PITTSBURGH,PITTSBURGH,PA 15213. VET ADM MED CTR,CINCINNATI,OH 45220. NINCDS,BETHESDA,MD 20892. RI Kling, Mitchel/F-4152-2010 OI Kling, Mitchel/0000-0002-2232-1409 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 181 EP 181 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900183 ER PT J AU Goldman, D Urbanek, M Guenther, D Robin, R Long, J AF Goldman, D Urbanek, M Guenther, D Robin, R Long, J TI A test of the DRD2 ''reward deficiency gene'' hypothesis with Ser311Cys SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIAAA,NEUROGENET LAB,NIH,ROCKVILLE,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 184 EP 184 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900187 ER PT J AU Bertolino, A Kumra, S Callicott, J Mattay, V Jacobsen, L Frank, J Rapoport, JL Weinberger, DR AF Bertolino, A Kumra, S Callicott, J Mattay, V Jacobsen, L Frank, J Rapoport, JL Weinberger, DR TI Proton magnetic resonance spectroscopic imaging in childhood onset schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,CLIN BRAIN DISORDERS BRANCH,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 201 EP 201 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900203 ER PT J AU Giedd, JN Castellanos, FX Jacobsen, LK Frazier, JA Hamburger, SD Rapoport, JL AF Giedd, JN Castellanos, FX Jacobsen, LK Frazier, JA Hamburger, SD Rapoport, JL TI Regional gray matter volumes in childhood onset schizophrenia and ADHD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 203 EP 203 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900205 ER PT J AU Neumeister, A PraschakRieder, N Hesselmann, B Vitouch, O Rauh, M Kasper, S AF Neumeister, A PraschakRieder, N Hesselmann, B Vitouch, O Rauh, M Kasper, S TI Serotonergic mechanisms in total sleep deprivation SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. UNIV VIENNA,DEPT GEN PSYCHIAT,A-1010 VIENNA,AUSTRIA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 212 EP 212 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900214 ER PT J AU Bertolino, A Adler, C Callicott, J Santha, A Podell, D Malhotra, A Mattay, V Pickar, D Frank, J Breier, A Weinberger, DR AF Bertolino, A Adler, C Callicott, J Santha, A Podell, D Malhotra, A Mattay, V Pickar, D Frank, J Breier, A Weinberger, DR TI Effects of ketamine on working memory circuitry as studied by whole brain fMRI SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,CLIN BRAIN DISORDERS BRANCH,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 218 EP 218 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900220 ER PT J AU Adler, CM Malhotra, AK Goldberg, T Elman, I Weinberger, D Pickar, D Breier, A AF Adler, CM Malhotra, AK Goldberg, T Elman, I Weinberger, D Pickar, D Breier, A TI Effects of the NMDA antagonist, ketamine on thought disorder and cognition SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,EXPT THERAPEUT BRANCH,BETHESDA,MD 20892. NIMH,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 222 EP 222 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900224 ER PT J AU Neumeister, A PraschakRieder, N Hesselmann, B Vitouch, O Rauh, M Kasper, S AF Neumeister, A PraschakRieder, N Hesselmann, B Vitouch, O Rauh, M Kasper, S TI Serotonergic dysfunction in SAD: Trait or state marker? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. UNIV VIENNA,DEPT GEN PSYCHIAT,A-1010 VIENNA,AUSTRIA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 240 EP 240 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900242 ER PT J AU Malhotra, AK Adler, CM Clifton, A Elman, I Pickar, D Breier, A AF Malhotra, AK Adler, CM Clifton, A Elman, I Pickar, D Breier, A TI Clozapine blunts NMDA antagonist-induced psychosis: A study with ketamine SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,UNIT PHARMACOGENET,EXPT THERAPEUT BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 247 EP 247 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900249 ER PT J AU George, MS Speer, AM Stallings, L Wassermann, EM Kimbrell, TA Epstein, C Risch, SC Post, RM AF George, MS Speer, AM Stallings, L Wassermann, EM Kimbrell, TA Epstein, C Risch, SC Post, RM TI Combining transcranial magnetic stimulation with functional imaging SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 MED UNIV S CAROLINA,DEPT PSYCHIAT,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT RADIOL,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT NEUROL,CHARLESTON,SC 29425. RALPH H JOHNSON VET AFFAIRS MED CTR,DEPT PSYCHIAT,CHARLESTON,SC. NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NINCDS,HUMAN MOTOR CONTROL SECT,BETHESDA,MD 20892. EMORY UNIV,DEPT NEUROL,ATLANTA,GA 30322. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 261 EP 261 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900262 ER PT J AU Post, RM Weiss, SRB Smith, M Zhang, LX Kimbrell, T Dunn, R McCann, U AF Post, RM Weiss, SRB Smith, M Zhang, LX Kimbrell, T Dunn, R McCann, U TI Sensitizing, kindling, and quenching effects of early experience SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,BIOL PSYCHIAT BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 264 EP 264 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900265 ER PT J AU Little, JT Ketter, TA Kimbrell, TA Danielson, AL Benson, BE Willis, MW Dunn, RT Frye, MA Post, RM AF Little, JT Ketter, TA Kimbrell, TA Danielson, AL Benson, BE Willis, MW Dunn, RT Frye, MA Post, RM TI Anterior paralimbic blood flow decreased after venlafaxine response SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. STANFORD UNIV,SCH MED,STANFORD,CA 94305. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 270 EP 270 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900271 ER PT J AU Baumann, MH Ayestas, MA Dersch, CM Brockington, A Rothman, RB AF Baumann, MH Ayestas, MA Dersch, CM Brockington, A Rothman, RB TI Anorectic amphetamines differentially affect monoamine function: Therapeutic implications SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIDA,CLIN PSYCHOPHARMACOL SECT,IRP,NIH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 324 EP 324 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900324 ER PT J AU Heinz, A Knable, MB Weinberger, DR AF Heinz, A Knable, MB Weinberger, DR TI Psychomotor slowing and dopamine receptor availability in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,WASHINGTON,DC 20032. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 347 EP 347 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900347 ER PT J AU Stanislav, SW Crismon, ML Childs, N Linnoila, M AF Stanislav, SW Crismon, ML Childs, N Linnoila, M TI CSF monoamine metabolites and post-traumatic aggression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 UNIV TEXAS,COLL PHARM,AUSTIN,TX 78712. HEALTHCARE REHABIL CTR,AUSTIN,TX 78745. NIAAA,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 357 EP 357 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900357 ER PT J AU Umhau, J George, DT Porges, S Reed, S Rawlings, R Linnoila, M AF Umhau, J George, DT Porges, S Reed, S Rawlings, R Linnoila, M TI Autonomic nervous system function in perpetrators of domestic violence SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIAAA,CLIN STUDIES LAB,BETHESDA,MD 20892. UNIV MARYLAND,INST CHILD STUDY,COLLEGE PK,MD 20742. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 358 EP 358 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900358 ER PT J AU Hauser, P Solar, R BruckerDavis, F AF Hauser, P Solar, R BruckerDavis, F TI Thyroid hormones correlate with symptoms of hyperactivity but not inattention in ADHD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 UNIV MARYLAND,MED CTR,BALTIMORE,MD 21201. BALTIMORE VA MED CTR,BALTIMORE,MD 21201. NIDDK,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 359 EP 359 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900359 ER PT J AU Kimbrell, TA George, MS Danielson, AL Dunn, RT Benson, BE Little, JT Herscovitch, P Hallett, M Post, RM Wassermann, EM AF Kimbrell, TA George, MS Danielson, AL Dunn, RT Benson, BE Little, JT Herscovitch, P Hallett, M Post, RM Wassermann, EM TI Changes in cerebral metabolism during transcranial magnetic stimulation SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. MED UNIV S CAROLINA,CHARLESTON,SC 29425. NIH,PET DEPT,BETHESDA,MD 20892. NINCDS,MOTOR CONTROL SECT,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 374 EP 374 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900373 ER PT J AU Ohuoha, DC Brockington, A Elmer, G Rothman, RB AF Ohuoha, DC Brockington, A Elmer, G Rothman, RB TI Serotonin-4 antagonists (GR113808A and GR125487D) and cocaine toxicity SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIDA,CLIN PSYCHOPHARMACOL SECT,DIR,NIH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 380 EP 380 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900379 ER PT J AU George, D Sirocco, K Eckardt, M Linnoila, M AF George, D Sirocco, K Eckardt, M Linnoila, M TI Age of onset for alcoholism and CSF homovanillic acid concentrations predict relapse SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIAAA,CLIN STUDIES LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 383 EP 383 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900382 ER PT J AU Ragan, PW George, DT Murphy, DL Linnoila, M AF Ragan, PW George, DT Murphy, DL Linnoila, M TI Influence of smoking on behavioral responses to m-CPP in alcoholic women SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIAAA,CLIN STUDIES LAB,NIH,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 384 EP 384 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900383 ER PT J AU Elman, I Goldstein, DS Holmes, C Pickar, D Adler, C Breier, A AF Elman, I Goldstein, DS Holmes, C Pickar, D Adler, C Breier, A TI Clozapine-induced elevation in norepinephrine: Relation to arterial plasma spillover SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,EXPT THERAPEUT BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 401 EP 401 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900400 ER PT J AU Roca, CA Schmidt, PJ Rubinow, DR AF Roca, CA Schmidt, PJ Rubinow, DR TI Drug discrimination of gonadal steroids in menopausal women SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,BEHAV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1997 VL 41 SU 7 BP 410 EP 410 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WQ709 UT WOS:A1997WQ70900408 ER PT J AU Jonnalagadda, SS terHaar, E Hamel, E Lin, CM Magarian, RA Day, BW AF Jonnalagadda, SS terHaar, E Hamel, E Lin, CM Magarian, RA Day, BW TI Synthesis and biological evaluation of 1,1-dichloro-2,3-diarylcyclopropanes as antitubulin and anti-breast cancer agents SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID ANALOG-II; ANEUPLOIDY INDUCTION; PURE ANTIESTROGENS; ANTITUMOR AGENTS; MICROTUBULE; STILBENEDIOL; DERIVATIVES; ESTROGENS; TAMOXIFEN; TUBULIN AB Z-1,1-Dichloro-2,3-diphenylcyclopropane (1) is an effective 'anti-breast cancer agent in rodents and in cell culture. We recently determined that 1 inhibits tubulin assembly in vitro. and causes microtubule loss in breast cancer cells, leading to accumulation in the G2/M portion of the cell cycle. Aryl ring-halogenated, methoxylated and benzyloxylated derivatives of 1, as well as its E-isomer and the dichlorocyclopropyl derivative of diethylstilbestrol (DES), were synthesized and tested for their ability to inhibit the assembly of tubulin into micro tubules. Including 1, 17 cyclopropyl compounds were tested. One (Z-1,1-dichloro-2-(4-methoxyphenyl)-3-phenylcyclopropane (12)) was found to be more active than 1. In addition, E-1,1-dichlorocyclopropylDES (17) was more potent than DES. The E-isomer of 1 (16) was inactive. The cytostatic activities of the compounds against MCF-7 and MDA-MB231 human breast cancer cells, and their abilities to perturb microtubules in MCF-7 cells were also evaluated. Z-Dichloro-2-(4-fluorophenyl)-3-phenylcyclo (5), Z-1,1-dichloro-2-(4-fluorophenyl)-3-(4-methoxyphenyl)cyclopropane (11), and Z-1,1-dichloro-2-(4-methoxyphenyl) -3-phenylcyclopropane (12) were more potent than 1 against the breast cancer cells. (C) 1997 Elsevier Science Ltd. C1 UNIV PITTSBURGH,DEPT ENVIRONM & OCCUPAT HLTH,PITTSBURGH,PA 15238. UNIV PITTSBURGH,DEPT PHARMACEUT SCI,PITTSBURGH,PA 15238. UNIV PITTSBURGH,INST CANC,PITTSBURGH,PA 15238. NCI,FREDERICK CANC RES & DEV CTR,LAB DRUG DISCOVERY RES & DEV,DIV CANC TREATMENT DIAGNOSIS & CTR,FREDERICK,MD 21702. UNIV OKLAHOMA,HLTH SCI CTR,DEPT MED CHEM & PHARMACEUT,OKLAHOMA CITY,OK 73190. FU NCI NIH HHS [CA 57288] NR 17 TC 21 Z9 22 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD APR PY 1997 VL 5 IS 4 BP 715 EP 722 DI 10.1016/S0968-0896(97)00014-X PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA XA930 UT WOS:A1997XA93000011 PM 9158870 ER PT J AU Paternostre, M Viard, M Meyer, O Ghanam, M Ollivon, M Blumenthal, R AF Paternostre, M Viard, M Meyer, O Ghanam, M Ollivon, M Blumenthal, R TI Solubilization and reconstitution of vesicular stomatitis virus envelope using octylglucoside SO BIOPHYSICAL JOURNAL LA English DT Article ID PH-DEPENDENT FUSION; INDUCED CELL-FUSION; MEMBRANE-FUSION; INFLUENZA HEMAGGLUTININ; OCTYL GLUCOSIDE; CONFORMATIONAL-CHANGES; BIOLOGICAL-MEMBRANES; SUBUNIT INTERACTIONS; MIXED MICELLES; LIPID BILAYERS AB Reconstituted vesicular stomatitis virus envelopes or virosomes are formed by detergent removal from solubilized intact virus. We have monitored the solubilization process of the intact vesicular stomatitis virus by the nonionic surfactant octylglucoside at various initial virus concentrations by employing turbidity measurements, This allowed us to determine the phase boundaries between the membrane and the mixed micelles domains, We have also characterized the lipid and protein content of the solubilized material and of the reconstituted envelope. Both G and M proteins and all of the lipids of the envelope were extracted by octylglucoside and recovered in the reconstituted envelope. Fusion activity of the virosomes tested either on Vero cells or on liposomes showed kinetics and pH dependence similar to those of the intact virus. C1 NCI,NATL INST HLTH,MATH BIOL LAB,BETHESDA,MD 20892. RP Paternostre, M (reprint author), UNIV PARIS SUD,EQUIPE PHYSIOCHIM SYST POLYPHASES,URA CNRS 1218,5 RUE JB CLEMENT,F-92296 CHATENAY MALABR,FRANCE. NR 61 TC 34 Z9 34 U1 0 U2 4 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR PY 1997 VL 72 IS 4 BP 1683 EP 1694 PG 12 WC Biophysics SC Biophysics GA WP369 UT WOS:A1997WP36900019 PM 9083672 ER PT J AU Batenjany, MM OLeary, TJ Levin, IW Mason, JT AF Batenjany, MM OLeary, TJ Levin, IW Mason, JT TI Packing characteristics of two-component bilayers composed of ester- and ether-linked phospholipids SO BIOPHYSICAL JOURNAL LA English DT Article ID PHASE; DIHEXADECYLPHOSPHATIDYLCHOLINE; GEL; DIPALMITOYLPHOSPHATIDYLCHOLINE; MIXTURES; PHOSPHATIDYLCHOLINE; GLYCEROL; BEHAVIOR AB The miscibility properties of ether- and ester-linked phospholipids in two-component, fully hydrated bilayers have been studied by differential scanning calorimetry (DSC) and Raman spectroscopy, Mixtures of 1,2-di-O-hexadecyl-rac-glycero-3-phosphocholine (DHPC) with 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) and of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) with 1,2-di-O-hexadecyl-sn-glycero-3-phosphoethanolamine (DHPE) have been investigated. The phase diagram for the DPPC/DHPE mixtures indicates that these two phospholipids are miscible in all proportions in the nonrippled bilayer gel phase. In contrast, the DHPC/DPPE mixtures display two regions of gel phase immiscibility between 10 and 30 mol% DPPE, Raman spectroscopic measurements of DHPC/DPPE mixtures in the C-H stretching mode region suggest that this immiscibility arises from the formation of DHPC-rich interdigitated gel phase domains with strong lateral chain packing interactions at temperatures below 27 degrees C, However, in the absence of interdigitation, our findings, and those of others, lead to the conclusion that the miscibility properties of mixtures of ether- and ester-linked phospholipids are determined by the nature of the phospholipid headgroups and are independent of the character of the hydrocarbon chain linkages. Thus it seems unlikely that the ether linkage has any significant effect on the miscibility properties of phospholipids in biological membranes. C1 ARMED FORCES INST PATHOL,DEPT CELLULAR PATHOL,WASHINGTON,DC 20306. NATL INST ARTHRIT DIABET & DIGEST & KIDNEY DIS,CHEM PHYS LAB,NATL INST HLTH,BETHESDA,MD 20892. NR 21 TC 6 Z9 6 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR PY 1997 VL 72 IS 4 BP 1695 EP 1700 PG 6 WC Biophysics SC Biophysics GA WP369 UT WOS:A1997WP36900020 PM 9083673 ER PT J AU Cuda, G Pate, E Cooke, R Sellers, JR AF Cuda, G Pate, E Cooke, R Sellers, JR TI In vitro actin filament sliding velocities produced by mixtures of different types of myosin SO BIOPHYSICAL JOURNAL LA English DT Article ID SMOOTH-MUSCLE MYOSIN; INVITRO MOTILITY ASSAY; SKELETAL-MUSCLE; HEAVY-MEROMYOSIN; IN-VITRO; CYTOPLASMIC MYOSINS; FORCE GENERATION; STEP SIZE; PHOSPHORYLATION; MOVEMENT AB Using in vitro motility assays, we examined the sliding velocity of actin filaments generated by pairwise mixings of six different types of actively cycling myosins. In isolation, the six myosins translocated actin filaments at differing velocities. We found that only small proportions of a more slowly translating myosin type could significantly inhibit the sliding velocity generated by a myosin type that translocated filaments rapidly. In other experiments, the addition of noncycling, unphosphorylated smooth and nonmuscle myosin to actively translating myosin also inhibited the rapid sliding velocity, but to a significantly reduced extent. The data were analyzed in terms of a model derived from the original working cross-bridge model of A. F. Huxley. We found that the inhibition of rapidly translating myosins by slowly cycling was primarily dependent upon only a single parameter, the cross-bridge detachment rate at the end of the working powerstroke. In contrast, the inhibition induced by the presence of noncycling, unphosphorylated myosins required a change in another parameter, the transition rate from the weakly attached actomyosin state to the strongly attached state at the beginning of the cross-bridge power stroke. C1 NHLBI,MOL CARDIOL LAB,NIH,BETHESDA,MD 20892. WASHINGTON STATE UNIV,DEPT PURE & APPL MATH,PULLMAN,WA 99164. UNIV CALIF SAN FRANCISCO,DEPT BIOCHEM & BIOPHYS,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,CARDIOVASC RES INST,SAN FRANCISCO,CA 94143. POLICLIN MATER DOMINI,FAC MED,DIPARTIMENTO MED SPERIMENTALE & CLIN,I-88100 CATANZARO,ITALY. RI Cuda, Giovanni/F-5359-2012 OI Cuda, Giovanni/0000-0001-6313-1866 FU NHLBI NIH HHS [HL 32145]; NIAMS NIH HHS [AR39643] NR 51 TC 72 Z9 72 U1 0 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR PY 1997 VL 72 IS 4 BP 1767 EP 1779 PG 13 WC Biophysics SC Biophysics GA WP369 UT WOS:A1997WP36900028 PM 9083681 ER PT J AU Shiao, YH Buzard, GS Weghorst, CM Rice, JM AF Shiao, YH Buzard, GS Weghorst, CM Rice, JM TI DNA template as a source of artifact in the detection of p53 gene mutations using archived tissue SO BIOTECHNIQUES LA English DT Article ID AMPLIFICATION C1 NIH,BCDP,SAIC,FREDERICK,MD 21702. OHIO STATE UNIV,COLUMBUS,OH 43210. RP Shiao, YH (reprint author), NCI,FREDERICK CANC RES & DEV CTR,NIH,BLDG 538,ROOM 205,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 11 TC 14 Z9 14 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 APR PY 1997 VL 22 IS 4 BP 608 EP & PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WT815 UT WOS:A1997WT81500007 PM 9105605 ER PT J AU Mardiney, M Jackson, SH Spratt, SK Li, F Holland, SM Malech, HL AF Mardiney, M Jackson, SH Spratt, SK Li, F Holland, SM Malech, HL TI Enhanced host defense after gene transfer in the murine p47(phox)-deficient model of chronic granulomatous disease SO BLOOD LA English DT Article ID HEMATOPOIETIC STEM-CELLS; BONE-MARROW TRANSPLANTATION; NADPH OXIDASE; PSEUDOMONAS-CEPACIA; LYMPHOCYTES-B; EXPRESSION; 5-FLUOROURACIL; INFECTION; VIRUS; MICE AB The p47(Phox-/-) mouse exhibits a phenotype similar to that of human chronic granulomatous disease (CGD) and, thus, is an excellent model for the study of gene transfer technology. Using the Moloney murine leukemia virus-based retroviral vector MFG-S encoding the human form of p47(phox), We performed ex vivo gene transfer into Sca-1(+) p47(phox-/-) marrow progenitor cells without conditioning of donors with 5-fluorouracil. Transduced progenitors were transplanted into moderately irradiated (500 cGy), G-CSF preconditioned sibling p47(Phox-/-) mice. Using the fluorescent probe dihydrorhodamine 123 (DHR), in vivo biochemical correction of the superoxide-generating NADPH oxidase system was detected by flow cytometry in 12.3% +/- 0.9% of phorbol myristate acetate-stimulated peripheral blood neutrophils at 4 weeks and 2.6% +/- 1.0% at 14 weeks after transplantation. Following gene therapy, mice were challenged with the CGD pathogen Burkholderia (formerly Pseudomonas) cepacia and bacteremia levels were assessed at 24 hours and 7 days after inoculation, At both time points, bacteremia levels in gene corrected p47(phox-/-) mice were significantly lower than untreated p47(phox-/-) mice (0.89 +/- 0.30 colonies v 237.7 +/- 83.6 colonies at 24 hours, P<.02; 4.0 +/- 2.0 colonies v 110.2 +/- 26.5 colonies at 7 days, P<.0014). More importantly, Kaplan-Meier survival analysis showed a significant survival advantage of gene corrected versus untreated p47(Phox-/-) mice (P<.001). Thus, stem-cell-directed ex vivo gene therapy is capable of restoring phagocyte oxidant-dependent host-defense function in this mouse model of a human immune-system disorder. C1 NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. SOMATIX THERAPY CORP,ALAMEDA,CA. NR 55 TC 99 Z9 101 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 1997 VL 89 IS 7 BP 2268 EP 2275 PG 8 WC Hematology SC Hematology GA WQ359 UT WOS:A1997WQ35900003 PM 9116268 ER PT J AU Salomon, DR Crisa, L Mojcik, CF Ishii, JK Klier, G Shevach, EM AF Salomon, DR Crisa, L Mojcik, CF Ishii, JK Klier, G Shevach, EM TI Vascular cell adhesion molecule-1 is expressed by cortical thymic epithelial cells and mediates thymocyte adhesion. Implications for the function of alpha 4 beta 1 (VLA4) integrin in T-cell development SO BLOOD LA English DT Article ID MARROW STROMAL CELLS; LATE ACTIVATION ANTIGEN-4; CYTOKINE PRODUCTION; SPLICED DOMAIN; BINDING-SITE; FIBRONECTIN; LYMPHOCYTES; EVENTS; SELECTION; RECEPTOR AB T-cell development requires a series of discrete selection and activation signals delivered to maturing progenitors in the thymic cortex and medulla. We have previously shown the constitutive activity of the integrin, alpha 4 beta 1 (VLA4), on a unique subpopulation of immature cortical thymocytes and proposed a role for integrin-mediated adhesion in positive selection by cortical epithelium, In the present report we show that thymic epithelial cell lines express vascular cell adhesion molecule-1 (VCAM-1) a high-affinity ligand for alpha 4 beta 1, and that VCAM-1 mediates thymocyte binding to these lines. Immunohistochemistry and confocal microscopy show that VCAM-1 is selectively expressed in situ by thymic epithelium in the cortex and corticomedullary junction, two locations at which VCAM-1 could determine the interaction between immature thymocytes and selecting elements on epithelial cells. In parallel, we confirmed that fibronectin (FN), the alternative ligand for alpha 4 beta 1, is expressed predominantly in the medulla, These results suggest that VCAM-1 is an adhesive ligand in the thymic cortex for the activated form of alpha 4 beta 1 constitutively expressed during development by immature double positive thymocytes. The structural segregation of the alternative ligand, FN, to the medulla suggests that medullary FN may regulate the migration, development, and export of more mature thymocytes. (C) 1997 by The American Society of Hematology. C1 Scripps Res Inst, DEPT IMMUNOL, LA JOLLA, CA 92037 USA. NIAID, IMMUNOL LAB, CELLULAR IMMUNOL SECT, NIH, BETHESDA, MD 20892 USA. Scripps Res Inst, DEPT CELL BIOL, LA JOLLA, CA USA. RP Salomon, DR (reprint author), Scripps Res Inst, DEPT MOL & EXPT MED SBR5, 10550 N TORREY PINES RD, LA JOLLA, CA 92037 USA. RI Salomon, Daniel/E-9380-2012 FU NIDDK NIH HHS [DK1820] NR 57 TC 44 Z9 45 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 APR 1 PY 1997 VL 89 IS 7 BP 2461 EP 2471 PG 11 WC Hematology SC Hematology GA WQ359 UT WOS:A1997WQ35900025 PM 9116290 ER PT J AU Gong, MK Yess, J Connolly, T Ivy, SP Ohnuma, T Cowan, KH Moscow, JA AF Gong, MK Yess, J Connolly, T Ivy, SP Ohnuma, T Cowan, KH Moscow, JA TI Molecular mechanism of antifolate transport-deficiency in a methotrexate-resistant MOLT-3 human leukemia cell line SO BLOOD LA English DT Article ID REDUCED FOLATE CARRIER; BINDING-PROTEIN; KB CELLS; CDNA; CLONING; SENSITIVITY; CANCER; PLACENTA; MEMBRANE; SEQUENCE AB Ohnuma et al reported a series of methotrexate-resistant MOLT-3 human T-cell acute lymphoblastic leukemia cell lines that showed decreasing methotrexate (MTX) uptake as the sublines acquired increasing MTX resistance (Cancer Res 45:1815, 1985). The alteration of MTX uptake kinetics in these cells, the intermediately resistant MOLT-3/MTX(200) and the highly resistant MOLT-3/MTX(10,000) cell lines, was attributed to a change in Vmax for methotrexate transport, without an apparent change in affinity of the transporter for MTX. We studied these cell lines to determine whether alteration of transcription or translation of the recently isolated reduced folate carrier gene (RFC1) was the cause of MTX transport deficiency in these cell lines. Reconstitution of RFC activity in MOLT-3/MTX(10,000) cells by transduction with a murine RFC retroviral vector reversed MTX resistance and trimetrexate sensitivity. Although RFC1 RNA levels were unchanged in the resistant cell lines, FACS analysis using a polyclonal anti-RFC1 antibody showed no detectable RFC1 protein in the MOLT-3/MTX(10,000) cells. Determination of the nucleotide sequence of RFC1 genes from MOLT-3/MTX(10,000) cells revealed that this cell line contained 3 RFC1 alleles: a wild-type allele, an allele containing the premature stop codon at codon 40 and a third allele containing another mutation, which resulted in a premature stop codon at codon 25. We examined the relative expression of these alleles by determining the nucleotide sequence of 24 RFC1 cDNA subclones from MOLT-3/MTX(10,000) cells and found that only one-third of these clones contained the wild-type sequence. Determination of the genomic sequence of RFC1 in MOLT-3/MTX(200) cells demonstrated that these cells were heterozygous for a mutation at codon 40, but were homozygous for the wild-type sequence at codon 25. Thus, the acquisition of MTX transport-deficiency in MOLT-3/MTX(10,000) cells results from inactivating mutations of RFC1 gene alleles. C1 NCI,MED BRANCH,NIH,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. CHILDRENS NATL MED CTR,WASHINGTON,DC 20010. MT SINAI SCH MED,DEPT MED,NEW YORK,NY. NR 18 TC 50 Z9 53 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 APR 1 PY 1997 VL 89 IS 7 BP 2494 EP 2499 PG 6 WC Hematology SC Hematology GA WQ359 UT WOS:A1997WQ35900029 PM 9116294 ER PT J AU Saxton, ML Longo, DL Wetzel, HE Tribble, H Alvord, WG Kwak, LW Leonard, AS Ullmann, CD Curti, BD Ochoa, AC AF Saxton, ML Longo, DL Wetzel, HE Tribble, H Alvord, WG Kwak, LW Leonard, AS Ullmann, CD Curti, BD Ochoa, AC TI Adoptive transfer of anti-CD3-activated CD4(+) T cells plus cyclophosphamide and liposome-encapsulated interleukin-2 cure murine MC-38 and 3LL tumors and establish tumor-specific immunity SO BLOOD LA English DT Article ID INTERFERON-GAMMA; COMPUTER-PROGRAM; KILLER-CELLS; ANTI-CD3; GROWTH; IMMUNOTHERAPY; RECOGNIZE; CARCINOMA; CLONES; CURVES AB The infusion of anti-CD3-activated murine T cells plus interleukin-2 (IL-2) exerts antitumor effects against several tumors in murine immunotherapy models. This study compares the therapeutic efficacy of anti-CD3-activated CD4(+) or CD8(+) T-cell subsets, when given with cyclophosphamide (Cy) and liposome-encapsulated IL-2 (L-IL2) in a murine model. C57BL/6 mice bearing subcutaneous (SC) MC-38 colon adenocarcinoma, 3LL Lewis lung carcinoma, or 38C13 lymphoma for 7 to 14 days were pretreated with low-dose intraperitoneal (IF) Cy before intravenous (IV) injection of anti-CD3-activated T cells or T-cell subsets. Cell administration was followed by IP administration of L-IL2 for 5 days, Mice receiving activated CD4(+) T cells showed significantly reduced tumor growth or complete remissions with prolonged disease-free survival in MC-38, 3LL, and 38C13. The timing of Cy doses in relation to adoptive transfer was critical in obtaining the optimal antitumor effect by CD4+ cells, Injecting Cy 4 days before the infusion of CD4+ cells greatly enhanced the antitumor effect of the CD4(+) cells and improved survival of the mice compared with other Cy regimens. C57BL/6 mice cured of MC-38 after treatment with CD4+ T cells developed tumor-type immunologic memory as demonstrated by their ability to reject rechallenges with MC-38, but not 3LL. Similarly, mice cured of 3LL tumors rejected rechallenges of 3LL, but not MC-38. The immunologic memory could be transferred with an IV injection of splenocytes from mice cured of MC-38 or 3LL. No cytotoxic T-lymphocyte activity was detected in T cells or T-cell subsets from mice cured of MC-38 or 3LL. Increased IL-2 and interferon-gamma (IFN-gamma) production was observed from CD4(+) subsets in cured animals when stimulated in vitro with the original tumor, but not with an unrelated syngeneic tumor. These results suggest that tumor-specific immunity can be achieved in vivo with anti-CD3-stimulated CD4(+) T cells in this cellular therapy model. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. SAIC INC,CLIN SERV PROGRAM,FREDERICK,MD. UNIV MINNESOTA,SCH MED,DEPT SURG,MINNEAPOLIS,MN 55455. BIOMIRA USA,CRANBURY,NJ. NR 27 TC 24 Z9 27 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 1997 VL 89 IS 7 BP 2529 EP 2536 PG 8 WC Hematology SC Hematology GA WQ359 UT WOS:A1997WQ35900034 PM 9116299 ER PT J AU Sivakumar, K SeminoMora, C Dalakas, MC AF Sivakumar, K SeminoMora, C Dalakas, MC TI An inflammatory, familial, inclusion body myositis with autoimmune features and a phenotype identical to sporadic inclusion body myositis - Studies in three families SO BRAIN LA English DT Article DE myositis, HLA antigens; autoimmune disease; inclusion body myositis; inherited susceptibility ID POLYMYOSITIS; MYOPATHIES; CELLS AB We describe the occurrence of an inflammatory inclusion body myositis in siblings of a single generation in three separate families. The disease in this total of seven patients was characterized by selective and early involvement of forearm and finger flexors, confirmed by MRI, and weakness of the quadriceps, triceps and foot extensors. Muscle biopsies in at least two members from each family showed endomysial inflammation red-rimmed vacuoles, intracellular amyloid deposition and 15-18-nm tubulofilaments within the vacuolated muscle fibres. Immunocytochemistry on serial muscle biopsy sections demonstrated an abundance of CD8+ cells invading non-necrotic, MHC-I-expressing muscle fibres. Immunogenetic studies showed the presence of the DR3 allele (DRB1*0301/0302) in all seven patients. The combination of the clinical, histological, immunopathological and immunogenetic features indicate that these patients have a disease identical to sporadic inclusion body myositis (s-IBM). We conclude that the classic inflammatory s-IBM can also occur in families (familial inclusion body myositis), in a pattern analogous to the familial occurrence of other autoimmune neurological diseases such as myasthenia gravis and multiple sclerosis. These observations strengthen the view that s-IBM behaves like other autoimmune diseases and has disease susceptibility linked to the DR3 allele. C1 NINCDS,NEUROMUSCULAR DIS SECT,NIH,BETHESDA,MD 20892. NR 28 TC 44 Z9 45 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0006-8950 J9 BRAIN JI Brain PD APR PY 1997 VL 120 BP 653 EP 661 DI 10.1093/brain/120.4.653 PN 4 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA WZ106 UT WOS:A1997WZ10600008 PM 9153127 ER PT J AU Wyler, B Shao, Y Schneider, E Cianfriglia, M Scheper, RJ Frey, BM Gieseler, F Schmid, L Twentyman, PR Lehnert, M AF Wyler, B Shao, Y Schneider, E Cianfriglia, M Scheper, RJ Frey, BM Gieseler, F Schmid, L Twentyman, PR Lehnert, M TI Intermittent exposure to doxorubicin in vitro selects for multifactorial non-P-glycoprotein-associated multidrug resistance in RPMI 8226 human myeloma cells SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE myeloma; multidrug resistance; doxorubicin ID DNA TOPOISOMERASE-II; HUMAN TUMOR-CELLS; MULTIPLE-MYELOMA; DRUG-RESISTANCE; PROTEIN MRP; POINT MUTATION; GENE; EXPRESSION; LINE; GLUTATHIONE AB The purpose of the present study was to evaluate whether intermittent exposure to a constant dose of doxorubicin selects for multidrug resistance (MDR) in RPMI 8226 human myeloma cells and, if so, to determine the molecular mechanism, In an attempt to approximate clinical doxorubicin treatment in vitro, cells were exposed to a fixed dose of doxorubicin for 4 d alternating with growth in drug-free medium for 17 d. An MDR subline emerged, termed 8226/DOXint5, which was 3-4-fold resistant to doxorubicin, etoposide and m-AMSA, and 1.6-fold resistant to vincristine. Sensitivity to docetaxel, melphalan and cisplatin was normal. Verapamil normalized vincristine sensitivity but had little effect on resistance to the other agents. Cellular uptake and retention of daunorubicin and vincristine were reduced by approximately 10%. The 8226/DOXint5 cells showed diminished DNA topoisomerase II alpha expression and increased expression of the multidrug resistance protein MRP. Expression of MDR1/P-glycoprotein was not detected. Immunostaining showed 70% of the cells to over-express the lung-resistance protein LRP. This new MDR myeloma cell line may prove to be a useful model for the development of strategies to overcome low-level, multifactorial MDR, which might be a common phenomenon in clinical myeloma treated with doxorubicin. C1 KANTONSSPITAL ST GALLEN,DEPT INTERNAL MED C,CANC RES LAB,CH-9007 ST GALLEN,SWITZERLAND. NCI,MED BRANCH,BETHESDA,MD 20892. IST SUPER SANITA,IMMUNOL LAB,I-00161 ROME,ITALY. UNIV WURZBURG,MED POLIKLIN,WURZBURG,GERMANY. INST CLIN CHEM & HAEMATOL,ST GALLEN,SWITZERLAND. MRC CTR,CLIN ONCOL & RADIOTHERAPEUT UNIT,CAMBRIDGE,ENGLAND. RI Gieseler, Frank/E-8386-2012; Gieseler, Frank/L-4668-2013 OI Gieseler, Frank/0000-0001-6409-3822; NR 67 TC 24 Z9 25 U1 1 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 1997 VL 97 IS 1 BP 65 EP 75 DI 10.1046/j.1365-2141.1997.52649.x PG 11 WC Hematology SC Hematology GA WV686 UT WOS:A1997WV68600009 PM 9136943 ER PT J AU Liu, TP Meredith, RF Saleh, MN Wheeler, RH Khazaeli, MB Plott, WE Schlom, J LoBuglio, AF AF Liu, TP Meredith, RF Saleh, MN Wheeler, RH Khazaeli, MB Plott, WE Schlom, J LoBuglio, AF TI Correlation of toxicity with treatment parameters for I-131-CC49 radioimmunotherapy in three phase II clinical trials SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS LA English DT Article DE biostatistics; cancer; clinical trials; monoclonal antibody; radioimmunotherapy; toxicity ID CARCINOMA; ANTIBODY; CC49 AB Analyses were performed on 40 patients with TAG-72 expressing metastatic cancer who were entered into three phase II clinical trials. The dose selected was the maximum tolerated dose in phase I studies. Patients all had unresectable metastatic colon or prostate cancer and had recovered from prior therapies. Patients in trials #1 and #2 received 75 mCi/M-2 I-131-CC49 antibody whereas those in trial #3 received a total of 75 mCi/m(2) with equal amounts of I-131-CC49 and I-131-COL-1. The three trials have resulted in a reproducible degree of reversible marrow suppression; 72.5% of patients experienced moderate or severe toxicity. Comparisons were made between demographic, clinical and pharmacokinetical variables and the grade of WBC toxicity platelet toxicity and the sum of the two as total toxicity. Whole body radiation dose had a statistically significant relationship with platelet toxicity (r=0.38, p=0.015) and total toxicity (r=0.34, p=0.035). The bone marrow radiation dose is significantly related to all toxicity indicators with correlation coefficients with WBC and platelet toxicities of 0.47 (p=0.002) and 0.34 (p=0.033), respectively. Plasma half-life had the strongest correlation with WBC toxicity and combined toxicities. Multivariate models were developed to help describe the simultaneous effect of these variables on toxicity. The results show that the MTD close was safely given to patients who varied in age, disease burden and degree of marrow compromise. This supports the contention that a fixed dose of radiolabeled antibody per body mass or m(2) can be given to a diverse group of non-lymphoma patients with a predictable toxicity range. C1 UNIV ALABAMA,CTR COMPREHENS CANC,WALLACE TUMOR INST 117,DEPT RADIAT ONCOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. NCI,BETHESDA,MD 20892. FU NCI NIH HHS [CA13148, CM47001] NR 23 TC 25 Z9 25 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1084-9785 J9 CANCER BIOTHER RADIO JI Cancer Biother. Radiopharm. PD APR PY 1997 VL 12 IS 2 BP 79 EP 87 DI 10.1089/cbr.1997.12.79 PG 9 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging GA XC359 UT WOS:A1997XC35900004 PM 10851451 ER PT J AU Kelloff, GJ Lubet, RA Fay, JR Steele, VE Boone, CW Crowell, JA Sigman, CC AF Kelloff, GJ Lubet, RA Fay, JR Steele, VE Boone, CW Crowell, JA Sigman, CC TI Farnesyl protein transferase inhibitors as potential cancer chemopreventives SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID K-RAS MUTATIONS; ABERRANT CRYPT FOCI; FAMILIAL ADENOMATOUS POLYPOSIS; SPORADIC COLORECTAL ADENOMAS; MONOTERPENE PERILLYL ALCOHOL; SIGNAL-TRANSDUCTION PATHWAY; POLYMERASE CHAIN-REACTION; ACUTE MYELOID-LEUKEMIA; ACTINOPLANIC-ACID-A; HUMAN BREAST-CANCER AB Among the most important targets for chemopreventive intervention and drug development are deregulated signal transduction pathways, Ras proteins serve as central connectors between signals generated at the plasma membrane and nuclear effecters; thus, disrupting the Ras signaling pathway could have significant potential as a cancer chemopreventive strategy, Target organs for Ras-based chemopreventive strategies include those associated with activating ras mutations (e.g., colorectum, pancreas, and lung) and those carrying aberrations in upstream element(s), such as growth factors and their receptors, Ras proteins require posttranslational modification with a farnesyl moiety for both normal and oncogenic activity, Inhibitors of the enzyme that catalyzes this reaction, farnesyl protein transferase (FPT) should, therefore, inhibit Ras-dependent proliferative activity in cancerous and precancerous lesions (J. B. Gibbs et al., Cell, 77: 175-178, 1994). Because growth factor networks are redundant, selective inhibition of signaling pathways activated in precancerous and cancerous cells should be possible. Requirements for Ras farnesylation inhibitors include: specificity for FPT compared with other prenyl transferases; specificity for FPT compared with other farnesyl PPi-utilizing enzymes; ability to specifically inhibit processing of mutant K-ras (the most commonly mutated ras gene in human canters); high potency; selective activity in intact cells; activity in vivo; and lack of toxicity. Numerous FPT inhibitors have been identified through random screening of natural products and by rational design of analogues of the two substrates, farnesyl PPi and the COOH-terminal CAAX motif of Ras tetrapeptides. A possible testing strategy for developing FPT inhibitors as chemopreventive agents includes the following steps: (a) determine FPT inhibitory activity in vitro; (b) evaluate selectivity (relative to other protein prenyl transferases and FPT-utilizing enzymes); (c) determine inhibition of Ras-mediated effects in intact cells; (d) determine inhibition of Ras-mediated effects in vivo (e.g., in nude mouse tumor xenografts); and (e) determine chemopreventive efficacy in vivo (e.g., in carcinogen-induced A/J mouse lung, rat colon, or hamster pancreas). C1 CCS ASSOCIATES, MT VIEW, CA USA. RP Kelloff, GJ (reprint author), NCI, CHEMOPREVENT BRANCH,DIV CANC PREVENT & CONTROL, EXECUT PLAZA N,SUITE 201, 6130 EXECUT BLVD, ROCKVILLE, MD 20852 USA. NR 187 TC 43 Z9 43 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 1997 VL 6 IS 4 BP 267 EP 282 PG 16 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA WU161 UT WOS:A1997WU16100008 PM 9107432 ER PT J AU Middelton, LA Peters, KF Helmbold, EA AF Middelton, LA Peters, KF Helmbold, EA TI Programmed instruction: Genetics and gene therapy - Genes and inheritance SO CANCER NURSING LA English DT Article DE genes; chromosomes; pedigree; mutation; inheritance AB The information gained from the Human Genome Project and related genetic research will undoubtedly create significant changes in health care practice, It is becoming increasingly clear that nurses in all areas of clinical practice will require a fundamental understanding of basic generics, This self-learning module provides the oncology nurse with an overview of basic genetic concepts including inheritance patterns of single gene conditions, pedigree construction, chromosome aberrations, ann the multifactorial basis underlying many common diseases of adulthood Normal gene structure and function will be introduced and the biochemistry of genetic errors will be described. C1 UNIV MICHIGAN,MED CTR,CLIN TRIALS CTR,ANN ARBOR,MI 48109. RP Middelton, LA (reprint author), NIH,PROGRAM DEV & MANAGEMENT,NATL HUMAN GENOME RES INST,BLDG 10,BETHESDA,MD 20892, USA. NR 7 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD APR PY 1997 VL 20 IS 2 BP 129 EP 151 DI 10.1097/00002820-199704000-00008 PG 23 WC Oncology; Nursing SC Oncology; Nursing GA WX248 UT WOS:A1997WX24800008 PM 9145562 ER PT J AU Tirkkonen, M Johannsson, O Agnarsson, BA Olsson, H Ingvarsson, S Karhu, R Tanner, M Isola, J Barkardottir, RB Borg, A Kallioniemi, OP AF Tirkkonen, M Johannsson, O Agnarsson, BA Olsson, H Ingvarsson, S Karhu, R Tanner, M Isola, J Barkardottir, RB Borg, A Kallioniemi, OP TI Distinct somatic genetic changes associated with tumor progression in carriers of BRCA1 and BRCA2 germ-line mutations SO CANCER RESEARCH LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; SEQUENCE COPY NUMBER; BREAST-CANCER; OVARIAN-CANCER; CHROMOSOME 13Q12-13; ALLELE LOSS; FAMILIES AB BRCA1 and BRCA2 mutations confer increased risk for development of breast cancer, but a number of additional, currently largely unknown, somatic genetic defects must also accumulate in the breast epithelial cells before malignancy develops. To evaluate the nature of these additional somatic genetic defects, we performed a genome-wide survey by comparative genomic hybridization on breast cancers from 21 BRCA1 mutation carriers, 15 BRCA2 mutation carriers, and 55 unselected controls, The total number of genetic changes was almost two times higher in tumors from both BRCA1 and BRCA2 mutation carriers than in the control group. In BRCA1 tumors, losses of 5q (86%), 4q (81%), 4p (61%), 2q (40%), and 12q (40%) were significantly more common than in the control group (7-13%). BRCA2 tumors were characterized by a higher frequency of 13q (73%) and 6q (60%) losses and gains of 1.7q22-q24 (87%) and 20q13 (60%) as compared to the prevalence of these changes in the control group (12-18%). In conclusion, accumulation of somatic genetic changes during tumor progression may follow a unique pathway in individuals genetically predisposed to cancer, especially by the BRCA1 gene, Activation or loss of genes in the affected chromosomal regions may be selected for during tumor progression in cells lacking functional BRCA1 or BRCA2. Identification of such genes could provide targets for therapeutic intervention and early diagnosis. C1 TAMPERE UNIV HOSP,INST MED TECHNOL,CANC GENET LAB,FIN-33101 TAMPERE,FINLAND. TAMPERE UNIV,FIN-33101 TAMPERE,FINLAND. UNIV LUND HOSP,DEPT ONCOL,S-22185 LUND,SWEDEN. UNIV ICELAND HOSP,DEPT PATHOL,CELL BIOL LAB,IS-121 REYKJAVIK,ICELAND. NIH,CANC GENET LAB,NATL HUMAN GENOME RES INST,BETHESDA,MD 20892. RI Kallioniemi, Olli/H-5111-2011; Ingvarsson, Sigurdur/E-7448-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 32 TC 301 Z9 305 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 1997 VL 57 IS 7 BP 1222 EP 1227 PG 6 WC Oncology SC Oncology GA WQ625 UT WOS:A1997WQ62500003 PM 9102202 ER PT J AU Samaha, HS Kelloff, GJ Steele, V Rao, CV Reddy, BS AF Samaha, HS Kelloff, GJ Steele, V Rao, CV Reddy, BS TI Modulation of apoptosis by sulindac, curcumin, phenylethyl-3-methylcaffeate, and 6-phenylhexyl isothiocyanate: Apoptotic index as a biomarker in colon cancer chemoprevention and promotion SO CANCER RESEARCH LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; CAFFEIC ACID; CELL-DEATH; DNA FRAGMENTATION; DIETARY CURCUMIN; TUMOR PROMOTION; PROTEIN-KINASE; CARCINOGENESIS; INHIBITION; MICE AB Recent evidence supports the theory that tumor growth in vivo depends on evasion of normal homeostatic control mechanisms that operate through induction of cell death by apoptosis, This study tested the hypothesis that several potential chemopreventive agents share the ability to induce apoptosis and that inhibition of apoptosis is a mechanism of tumor promoters. The present study was designed to investigate whether the chemopreventive properties of sulindac, curcumin, and phenylethyl-3-methylcaffeate (PEMC) and the tumor-promoting activity of 6-phenyl-hexyl isothiocyanate (PHITC) that were observed in our previous studies are associated with the induction or inhibition of apoptosis in azoxymethane (AOM)-induced colon tumors in male F344 rats, At 5 weeks of age, groups of rats were fed control (modified AIN-76A) diet or diets containing 320 ppm of sulindac, 2000 ppm of curcumin, 750 ppm of PEMC, or 640 ppm of PHITC, At 7 weeks of age, all rats except those intended for vehicle (normal saline) treatment were given AOM (15 mg/kg body weight) once weekly for 2 weeks, To study the effect of sulindac administered during promotion/progression stage, the rats were fed the control diet initially and then fed the experimental diet containing 320 ppm of sulindac 14 weeks after the second AOM treatment, The rats were sacrificed 52 weeks after carcinogen treatment, and their colonic tumors were subjected to histopathological evaluation and the appearance of apoptosis, In the current study, chronic administration of sulindac, curcumin, and PEMC or sulindac given only during promotion/progression significantly increased the apoptotic index (percentage of apoptosis) as compared to administration of the control diet; the apoptotic indices in the control, sulindac, curcumin, and PEMC diets were 8.3, 17.6, 17.7, and 18.5%, respectively, and in sulindac administered during promotion/progression stage, the apoptotic index was 19.1%, However, dietary PHITC blocked the process of apoptosis during colon carcinogenesis, The apoptotic index in PHITC diet was 7.0%, Taken together, our data show that chemopreventive properties of agents are correlated with the degree of apoptosis, Therefore apoptosis seems to be a reliable biomarker for the evaluation of potential agents for cancer prevention. C1 AMER HLTH FDN,DIV NUTR CARCINOGENESIS,VALHALLA,NY 10595. NCI,CHEMOPREVENT BRANCH,BETHESDA,MD 20892. RI Chinthalapally, Rao/B-3633-2010 FU NCI NIH HHS [CA-17613, CN-85095-05, CN-85095-07] NR 49 TC 249 Z9 258 U1 1 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 APR 1 PY 1997 VL 57 IS 7 BP 1301 EP 1305 PG 5 WC Oncology SC Oncology GA WQ625 UT WOS:A1997WQ62500018 PM 9102217 ER PT J AU Bagnato, A Tecce, R DiCastro, V Catt, KJ AF Bagnato, A Tecce, R DiCastro, V Catt, KJ TI Activation of mitogenic signaling by endothelin 1 in ovarian carcinoma cells SO CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE-C; RAT-KIDNEY CELLS; TYROSINE PHOSPHORYLATION; MAP KINASE; LYSOPHOSPHATIDIC ACID; GENE-EXPRESSION; MESANGIAL CELLS; STROMAL CELLS; GROWTH-FACTOR; CANCER CELLS AB Endothelin 1 (ET-1) is produced in ovarian cancer cell lines and has been shown to act through ET(A) receptors as an autocrine growth factor to promote tumor cell proliferation irt vitro. In OVCA 433 cells, the efficacy of ET-1 as a stimulus of [H-3]thymidine incorporation was equivalent to that of epidermal growth factor, ET-1 also stimulated the rapid expression of c-fos, an action mediated by ET(A) receptors. The mitogenic action of ET-1 was not mediated by a pertussis toxin-sensitive G protein, An analysis of the effects of inhibition and depletion of protein kinase C (PKC) on mitogenic responses demonstrated that PKC was necessary but not sufficient for maximal stimulation by ET-1. In quiescent OVCA 433 cells, ET-1-induced stimulation of [H-3]thymidine incorporation was prevented by two structurally distinct inhibitors of tyrosine kinase, herbimycin A and genistein, These results indicate that both PKC and protein tyrosine kinase participate in ET-1-stimulated mitogenic signaling, ET-1 rapidly stimulated tyrosine phosphorylation of several cellular proteins, among which p125(FAK) and p42 mitogen-activated protein kinase were identified, The additivity between the potent mitogenic actions of ET-1 and epidermal growth factor is consistent with the independence of their signal transduction pathways in ovarian cancer cells. These findings also indicate that intracellular signaling between the ET(A) receptor and a yet unidentified tyrosine kinase is involved in the mitogenic response to ET-1. C1 NIH,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. RP Bagnato, A (reprint author), REGINA ELENA INST CANC RES,LAB MOL PATHOL & ULTRASTRUCT,VIA MESSI ORO 156-158,I-00158 ROME,ITALY. RI Bagnato, Anna/G-9747-2016 OI Bagnato, Anna/0000-0002-7269-9522 NR 48 TC 105 Z9 106 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 1997 VL 57 IS 7 BP 1306 EP 1311 PG 6 WC Oncology SC Oncology GA WQ625 UT WOS:A1997WQ62500019 PM 9102218 ER PT J AU Bojes, HK Germolec, DR Simeonova, P Bruccoleri, A Schoonhoven, R Luster, MI Thurman, RG AF Bojes, HK Germolec, DR Simeonova, P Bruccoleri, A Schoonhoven, R Luster, MI Thurman, RG TI Antibodies to tumor necrosis factor alpha prevent increases in cell replication in liver due to the potent peroxisome proliferator, WY-14,643 SO CARCINOGENESIS LA English DT Article ID RAT KUPFFER CELLS; PROTEIN KINASE-C; GENE-EXPRESSION; DNA-SYNTHESIS; HYPOLIPIDEMIC DRUGS; CLOFIBRIC ACID; CARCINOGENESIS; MICE; REGENERATION; MACROPHAGES AB Several structurally dissimilar hypolipidemic drugs, plasticizers and halogenated hydrocarbons induce peroxisomes in hepatocytes, and cause hepatocellular adenoma and carcinoma in rats and mice, The mechanism by which these agents act is unknown, although recent studies have suggested a link between increased cell proliferation and hepatic cancer caused by peroxisome proliferators, Here, we demonstrate that neutralizing antibodies to tumor necrosis factor alpha (TNF alpha) block increases in protein kinase C and cell proliferation due to [4-chloro-6-(2,3-xylidido)-2-pyrimidinylthio]acetic acid (WY-14,643), a hypolipidemic drug and potent peroxisome proliferator that causes tumors, WY-14,643 moderately elevated the level of TNF alpha mRNA in the liver. TNF alpha was detected immunohistochemically exclusively in Kupffer cells, These results demonstrate that WY-14,643 acts as an indirect mitogen on hepatocytes via TNF Alpha. We propose that the Kupffer cell, a major source of TNF alpha in the liver, is involved in the mechanism of the mitogenic effect of WY-14,643. C1 UNIV N CAROLINA,DEPT PHARMACOL,HEPATOBIOL & TOXICOL LAB,CHAPEL HILL,NC 27599. UNIV N CAROLINA,CURICULUM TOXICOL,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT ENVIRONM SCI & ENGN,CHAPEL HILL,NC 27599. NIEHS,IMMUNOL & NEUROBIOL SECT,RES TRIANGLE PK,NC 27709. FU NIEHS NIH HHS [ES-04325] NR 39 TC 79 Z9 79 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 1997 VL 18 IS 4 BP 669 EP 674 DI 10.1093/carcin/18.4.669 PG 6 WC Oncology SC Oncology GA WT305 UT WOS:A1997WT30500010 PM 9111198 ER PT J AU Ghanayem, BI Elwell, MR Eldridge, SR AF Ghanayem, BI Elwell, MR Eldridge, SR TI Effects of the carcinogen, acrylonitrile, on forestomach cell proliferation and apoptosis in the rat: Comparison with methacrylonitrile SO CARCINOGENESIS LA English DT Article ID 2-CYANOETHYLENE OXIDE; GLUTATHIONE; METABOLISM; DNA AB Acrylonitrile (AN) and methacrylonitrile (MAN) are two major industrial nitriles used in the production of plastics and acrylic fibers, Whereas AN is a potent acute toxin and carcinogenic in rats, little is known regarding MAN, Current work is part of an overall effort designed to assess the potential toxicity/carcinogenicity of MAN, The present study compares the ability of the two chemicals to induce epithelial proliferation and apoptosis in the forestomach (FS; a target of AN carcinogenicity), liver and glandular stomach (non-targets of AN carcinogenicity) of male F344 rats, AN was administered to rats daily, by gavage, for 6 weeks, at 0.43 and 0.22 mmol/kg, MAN was administered at 0.87 and 0.43 mmol/kg, Both AN and MAN induced a dose-dependent increase in epithelial cell proliferation in the FS of male F344 rats as determined by bromodeoxyuridine (BrdU) incorporation into DNA, In contrast, AN, but not MAN caused a dose-dependent increase in the thickness of the forestomach squamous mucosa, This increased thickness (hyperplasia) was reflected by an increase in the number of total epithelial cells per unit length of mucosa, At doses of AN and MAN which induced a 2.3-fold increase in BrdU incorporation, apoptosis was 5- and 18-fold greater than controls, respectively, Although both MAN and AN caused a similar increase in cell proliferation, the relatively more prominent increase in the apoptotic index of the squamous epithelium of rats exposed to MAN may explain the lack of a detectable increase in the thickness of the mucosa compared to that seen with AN, The disruption of the balance between FS mucosal cell proliferation and apoptosis in favor of a net increase in the number of FS epithelial cells per unit length may contribute to the carcinogenicity of AN, In conclusion, present work demonstrated that AN selectively induced a net enhancement in FS cell proliferation, a site of its carcinogenicity, On the other hand, MAN-induced FS cell proliferation was associated with a parallel increase in apoptosis, The relatively greater increase in apoptosis by MAN may have compensated for the increase in FS mucosal cell proliferation and the lack of observable change in the FS thickness. C1 PAI,DURHAM,NC. RP Ghanayem, BI (reprint author), NIEHS,NIH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 32 TC 12 Z9 13 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 1997 VL 18 IS 4 BP 675 EP 680 DI 10.1093/carcin/18.4.675 PG 6 WC Oncology SC Oncology GA WT305 UT WOS:A1997WT30500011 PM 9111199 ER PT J AU Cullinane, C Weber, CA Dianov, G Bohr, VA AF Cullinane, C Weber, CA Dianov, G Bohr, VA TI Restoration of preferential and strand specific gene repair in group 2 Chinese hamster ovary mutants (UV5) by the XPD (ERCC2) gene SO CARCINOGENESIS LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; PIGMENTOSUM GROUP-D; COMPLEMENTATION GROUP-D; RNA-POLYMERASE-II; DNA-REPAIR; XERODERMA-PIGMENTOSUM; SACCHAROMYCES-CEREVISIAE; MOLECULAR CHARACTERIZATION; TRANSCRIPTION FACTOR; PYRIMIDINE DIMERS AB It has recently been reported that the XPD (ERCC2) gene is an integral component of the basal transcription factor TFIIH. We have studied the direct role of this repair gene on the fine structure of DNA repair in hamster cells, The gene and strand specific DNA repair of UV induced pyrimidine dimers was determined in wild-type hamster cells, in hamster cells harboring a mutation in the gene homologous to the XPD gene and in mutant cells transfected with the human XPD gene, In the mutant cells, strand specific repair was severely deficient. In the transfected cells, preferential and strand specific gene repair were restored to wild-type levels, The results of the current study clearly demonstrate a direct role for the XPD gene product both in the preferential repair and bulk repair of pyrimidine dimers as well as its high functional conservation between rodent and human cells. An in vitro transcription assay was employed to investigate whether RNA polymerase II mediated transcription was also affected by the transfection with the XPD gene, No change in transcription between the mutant and transfected cells was observed, This suggests that the role of XPD in repair can be distinguished from its role in TFIIH dependent transcription initiation, Different functional domains of XPD appear to be necessary for repair versus transcription. C1 LAWRENCE LIVERMORE NATL LAB,BIOL & BIOTECHNOL RES PROGRAM,LIVERMORE,CA 94551. RP Cullinane, C (reprint author), NIA,INST GENET MOL,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 46 TC 9 Z9 9 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 1997 VL 18 IS 4 BP 681 EP 686 DI 10.1093/carcin/18.4.681 PG 6 WC Oncology SC Oncology GA WT305 UT WOS:A1997WT30500012 PM 9111200 ER PT J AU Beecham, EJ Owens, JD Shaughnessy, JD Huppi, K Bohr, VA Mushinski, JF AF Beecham, EJ Owens, JD Shaughnessy, JD Huppi, K Bohr, VA Mushinski, JF TI Decoupling of DNA excision repair and RNA transcription in translocation breaksite regions of plasmacytoma-susceptible BALB/cAnPt mice SO CARCINOGENESIS LA English DT Article ID HAMSTER OVARY CELLS; PYRIMIDINE DIMERS; CHROMOSOMAL TRANSLOCATION; ACTIVE GENE; DHFR GENE; STRAND; REMOVAL; LOCUS; INDUCTION; INCREASES AB Preferential repair of pyrimidine dimers in rodent cells is thought to be directly coupled to the RNA transcription machinery, The most compelling evidence for this notion is the finding that excision repair occurs more rapidly in the template strand of DNA of transcribed genes than in the non-template strand, A thorough test of this coupling concept by careful comparison of the rate of repair to the rate of transcription of a gene and its regulatory region has not been reported, In the present study, we used nuclear run-on as a measure of transcription in the c-myc and Pvt1 genes in normal B-lymphoblasts from plasmacytoma-susceptible (BALB/cAnPt) and plasmacytoma-resistant (DBA/2N) strains of mice, Previous studies have shown that these loci, but not c-abl or Dhfr are repaired differently in mouse strains: poorly in BALB/cAnPt but efficiently in DBA/2N, The results presented here indicate that in DBA/2N cells, run-on transcription from both DNA strands can be readily detected in the regions of c-myc and Pvt1 that were efficiently repaired, Unexpectedly, however, in BALB/cAnPt lymphoblasts, transcription was equivalent to that of DBA/2N, despite a dramatic reduction in efficiency of excision repair, This finding indicates that, in BALB/cAnPt lymphoblasts, DNA repair 5' to c-myc and in Pvt1 is decoupled from the RNA transcription machinery, We postulate that this dissociation of repair and transcription represents a BALB/cAnPt-specific defect in a component of the transcription/repair complex that specifically compromises repair activity but not transcription, This defect may be responsible for the inability of normal BALB/cAnPt lymphoblasts to repair DNA sequences in the c-myc 5' flank and the Pvt1 gene, inducing gene-specific instability that predisposes these loci to genetic accidents, including chromosomal translocation, retroviral integration and other mutations. C1 NCI,GENET LAB,NIH,BETHESDA,MD 20892. NCI,MOL PHARMACOL LAB,NIH,BETHESDA,MD 20892. NR 30 TC 4 Z9 4 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 1997 VL 18 IS 4 BP 687 EP 694 DI 10.1093/carcin/18.4.687 PG 8 WC Oncology SC Oncology GA WT305 UT WOS:A1997WT30500013 PM 9111201 ER PT J AU Sorensen, IK Kristiansen, E Mortensen, A vanKranen, H vanKreijl, C Fodde, R Thorgeirsson, SS AF Sorensen, IK Kristiansen, E Mortensen, A vanKranen, H vanKreijl, C Fodde, R Thorgeirsson, SS TI Short-term carcinogenicity testing of a potent murine intestinal mutagen, 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), in Apc1638N transgenic mice SO CARCINOGENESIS LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; GERM-LINE MUTATIONS; APC GENE; COLORECTAL TUMORIGENESIS; SOMATIC MUTATIONS; COOKED FOOD; ALLELE LOSS; COLI GENE; CANCER; IDENTIFICATION AB Transgenic Apc1638N mice, heterozygous for a targeted frameshift mutation at codon 1638 of the endogenous adenomatous polyposis coli (APC) gene, are predisposed to develop multiple adenomas and adenocarcinomas along the intestinal tract and to a number of extra-intestinal lesions including, among others, mammary tumors, We have studied these mice in a short-term carcinogenicity test with 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), a potent murine small intestinal mutagen and lymphomagen. Upon dietary administration of 0.03% PhIP in a short-term (6 months) study, a significantly increased number of small intestinal tumors as well as an increased number of aberrant crypt foci (ACF) were observed in male Apc(+)/Apc1638N mice compared with untreated transgenic mice, No differences in intestinal and mammary tumor multiplicity were observed between treated and control Apc(+)/Apc1638N females. C1 NATL INST PUBL HLTH & ENVIRONM PROTECT,NL-3720 BA BILTHOVEN,NETHERLANDS. LEIDEN UNIV,DEPT HUMAN GENET,MGC,NL-2300 RA LEIDEN,NETHERLANDS. NCI,NIH,BETHESDA,MD 20892. RP Sorensen, IK (reprint author), NATL FOOD AGCY,INST TOXICOL,MORKHOJ BYGADE 19,DK-2860 SOBORG,DENMARK. OI Fodde, Riccardo/0000-0001-9839-4324 NR 44 TC 16 Z9 16 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 1997 VL 18 IS 4 BP 777 EP 781 DI 10.1093/carcin/18.4.777 PG 5 WC Oncology SC Oncology GA WT305 UT WOS:A1997WT30500026 PM 9111214 ER PT J AU Hong, HL Devereux, TR Melnick, RL Eldridge, SR Greenwell, A Haseman, J Boorman, GA Sills, RC AF Hong, HL Devereux, TR Melnick, RL Eldridge, SR Greenwell, A Haseman, J Boorman, GA Sills, RC TI Both K-ras and H-ras protooncogene mutations are associated with Harderian gland tumorigenesis in B6C3F1 mice exposed to isoprene for 26 weeks SO CARCINOGENESIS LA English DT Article ID CELL NUCLEAR ANTIGEN; INDUCED LUNG-TUMORS; TRANSGENIC MICE; INHALATION EXPOSURE; METHYLENE-CHLORIDE; MAMMARY-TUMORS; P53 MUTATIONS; ACTIVATION; GENE; RATS AB Isoprene is the 2-methyl analog of 1,3-butadiene, a genotoxic and carcinogenic compound in rats and mice, Male B6C3F1 mice were exposed to 0, 2200 or 7000 ppm isoprene by inhalation (6 h/day; 5 days/week) for 26 weeks, Following a 26-week recovery period, an increased incidence of Harderian gland (HG) neoplasms was observed at both concentrations, The present study was designed to characterize genetic alterations in the K-ras and H-ras protooncogenes in HG neoplasms, Mutations in K-ras and H-ras were identified by single-strand conformational analysis and direct sequencing of polymerase chain reaction (PCR) amplified DNA, isolated from paraffin-embedded sections of HG neoplasms, A higher frequency of ras mutations, in particular K-ras mutations, was detected in isoprene-induced neoplasms than in 1,3-butadiene-induced or control HG neoplasms, All of the isoprene-induced HG neoplasms exhibited activated K-ras (60%) or H-ras (40%) mutations, In contrast, ras mutations were detected in 69% of HG neoplasms from 1,3-butadiene exposed mice (14% K-ras and 55% H-ras) and in 56% of HG neoplasms obtained from control B6C3F1 mice (8% K-ras and 48% H-ras), The predominant mutations in isoprene-induced HG neoplasms, but not in previously or newly analysed 1,3-butadiene-induced HG neoplasms, consisted of A-->T transversions (CAA-->CTA) at K-ras codon 61 (15/30) and C-->A transversions (CAA-->AAA) at H-ras codon 61 (8/30), Two-thirds of the K-ras CTA mutations were detected in HG neoplasms from the 2200 ppm exposure group while one-third was present in the 7000 ppm group, Isoprene-induced HG neoplasms with K-ras or H-ras mutations had an elevated proliferating cell nuclear antigen (PCNA) index, compared to spontaneous HG neoplasms without ras mutations, The high frequency and specificity of the pas mutation profile suggest that ras protooncogene activation contributes to isoprene-induced HG tumorigenesis. C1 NIEHS,ENVIRONM CARCINOGENESIS PROGRAM,RES TRIANGLE PK,NC 27709. PATHOL ASSOCIATES INT,DURHAM,NC 27713. RP Hong, HL (reprint author), NIEHS,ENVIRONM TOXICOL PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 46 TC 19 Z9 20 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 1997 VL 18 IS 4 BP 783 EP 789 DI 10.1093/carcin/18.4.783 PG 7 WC Oncology SC Oncology GA WT305 UT WOS:A1997WT30500027 PM 9111215 ER PT J AU Freedman, AN Michalek, AM Troisi, R Mettlin, CJ Petrelli, NJ Asirwatham, JE Caporaso, N AF Freedman, AN Michalek, AM Troisi, R Mettlin, CJ Petrelli, NJ Asirwatham, JE Caporaso, N TI Oral contraceptives, reproductive factors and p53 gene expression in colorectal cancer SO CARCINOGENESIS LA English DT Article ID COLON-CANCER; BOWEL-CANCER; CARCINOGENESIS; EPIDEMIOLOGY; MUTATIONS; HORMONES; SMOKING; RISK AB Protective effects of oral contraceptives and high parity on the development of colorectal cancer have been hypothesized. However, the epidemiological data are inconsistent, This inconsistency may be due in part to the biological heterogeneity of colorectal tumors, A recent investigation of hepatocellular carcinoma demonstrated an association between lack of p53 expression and oral contraceptive use. We investigated the relationship between oral contraceptive use and other reproductive factors with p53 over-expression in 64 post-menopausal women, 45-86 years of age, with non-familial colorectal adenocarcinoma, Fifty per cent (32/64) of colorectal tumors displayed nuclear over-expression of p53 protein, Women with a history of oral contraceptive use were significantly less likely to have p53 positive (+) tumors than women who never used oral contraceptives (P = 0.02), In contrast, tumors from women who had never been pregnant were more likely to be p53 + compared to tumors from parous women (P = 0.10), These data suggest that oral contraceptive use and pregnancy are associated with a p53 independent pathway in the development of colorectal cancer. C1 ROSWELL PK CANC INST,DEPT SURG ONCOL,BUFFALO,NY 14263. ROSWELL PK CANC INST,DEPT EDUC AFFAIRS,BUFFALO,NY 14263. ROSWELL PK CANC INST,DEPT CANC CONTROL & EPIDEMIOL,BUFFALO,NY 14263. BUFFALO GEN HOSP,DEPT PATHOL,BUFFALO,NY 14203. RP Freedman, AN (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892, USA. NR 25 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 1997 VL 18 IS 4 BP 855 EP 856 DI 10.1093/carcin/18.4.855 PG 2 WC Oncology SC Oncology GA WT305 UT WOS:A1997WT30500037 PM 9111225 ER PT J AU Hughes, FM Cidlowski, JA AF Hughes, FM Cidlowski, JA TI Utilization of an in vitro assay to evaluate chromatin degradation by candidate apoptotic nucleases SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE apoptosis; cell death; endonuclease; nuclease assay ID RAT-LIVER NUCLEI; CALCIUM-DEPENDENT ENDONUCLEASE; KILOBASE PAIR FRAGMENTS; ACID CLEAVAGE ACTIVITY; PROGRAMMED CELL-DEATH; HIGH-MOLECULAR-WEIGHT; DNA FRAGMENTATION; DEOXYRIBONUCLEIC-ACID; INTERNUCLEOSOMAL FRAGMENTATION; IMMATURE THYMOCYTES AB Apoptosis is commonly associated with the catabolism of the genome in the dying cell. The chromatin degradation occurs in essentially two forms: (1) internucleosomal DNA cleavage to generate oligonucleosomal-length fragments (180-200 bp and multiples thereof), and (2) cleavage of higher order chromatin structures to generate approximate to 30-50 Kb fragments. To investigate this component of apoptosis and identify the nuclease(s) responsible, we have developed and utilized an in vitro assay that recapitulates the genomic destruction seen during apoptosis in vivo and allows the simultaneous analysis of both forms of DNA degradation from the same sample. Using this assay we evaluated the digestion patterns of several candidate apoptotic nucleases: DNase I, DNase II, and cyclophilin (NUC18) as well as the bacterial enzyme micrococcal nuclease (not thought to be involved in apoptosis). Chromatin degraded by DNase I formed a smear of DNA on conventional static-field agarose gels and approximate to 30-50 Kb DNA fragments on pulsed field gels. In contrast, DNase II, at a physiologically relevant pH, had no effect on the integrity of HeLa chromatin in either analysis. Similar to DNase I, cyclophilin C produced only approximate to 30-50 Kb DNA fragments but did not generate internucleosomal fragments. In contrast, micrococcal nuclease generated both oligonucleosomal and approximate to 30-50 Kb DNA fragments. Nuclear extracts from glucocorticoid-treated apoptotic thymocytes generated oligonucleosomal DNA fragments and the larger approximate to 30-50 Kb DNA fragments, fully recapitulating both types of apoptotic DNA degradation. Previously, differential sensitivity of nucleases to inhibition by Zn2+ was used to argue that two distinct enzymes mediate approximate to 30-50 Kb DNA cleavage and internucleosomal DNA degradation. While, the nuclease activity present in thymocyte nuclear extracts was differentially sensitive to inhibition by Zn2+ during short term incubations it was not during prolonged digestions, suggesting that differences in DNA detection are likely to account for previous results. Together our studies show that none of the nucleases commonly associated with apoptosis could fully recapitulate the DNA degradation seen in vivo. RP Hughes, FM (reprint author), NIEHS,LABS INTEGRAT BIOL,POB 12233,MD E2-02,RES TRIANGLE PK,NC 27709, USA. NR 49 TC 25 Z9 27 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD APR PY 1997 VL 4 IS 3 BP 200 EP 208 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA WR528 UT WOS:A1997WR52800005 PM 16465229 ER PT J AU Szeliga, J Hilton, BD Chmurny, GN Krzeminski, J Amin, S Dipple, A AF Szeliga, J Hilton, BD Chmurny, GN Krzeminski, J Amin, S Dipple, A TI Characterization of DNA adducts formed by the four configurationally isomeric 5,6-dimethylchrysene 1,2-dihydrodiol 3,4-epoxides SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID COVALENT NUCLEOSIDE ADDUCTS; REGION 3,4-DIOL 1,2-EPOXIDES; CHEMICAL CARCINOGENESIS; MOUSE SKIN; BENZOPYRENE 7,8-DIOL-9,10-EPOXIDES; 11,12-DIHYDRODIOL 13,14-EPOXIDE; DEOXYADENOSINE ADDUCTS; 7,8-DIOL 9,10-EPOXIDES; DIHYDRODIOL-EPOXIDES; CYTOSINE BASES AB The DNA adducts formed from the racemic syn and anti dihydrodiol epoxides of 5,6-dimethylchrysene were characterized through various spectroscopic methods. Substantial reaction with the amino groups of both deoxyadenosine and deoxyguanosine residues were detected with both the syn and anti derivatives. The chemical shifts and coupling constants for the cis and trans opened adducts from the syn dihydrodiol epoxide were distinctly different, whereas for the anti dihydrodiol epoxide these properties were fairly similar for cis and trans adducts. In the latter case, assignment of traits and cis configurations was less obvious, and the finding that trans adducts have always predominated over cis adducts for all dihydrodiol epoxides studied to date was helpful in making these assignments. The preferential formation of cis adducts in DNA by the syn dihydrodiol epoxide is more like the chemistry of the dihydrodiol epoxide of benzo[c]phenanthrene than of benzo[g]chrysene, although both of these, like 5,6-dimethylchrysene, are non-planar compounds. C1 NCI,FREDERICK CANC RES & DEV CTR,CHEM SYNTH & ANAL LAB,FREDERICK,MD 21702. AMER HLTH FDN,NAYLOR DANA INST DIS PREVENT,VALHALLA,NY 10595. RP Szeliga, J (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHEM CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. NR 33 TC 12 Z9 13 U1 0 U2 1 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 APR PY 1997 VL 10 IS 4 BP 378 EP 385 DI 10.1021/tx960178s PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA WU385 UT WOS:A1997WU38500005 PM 9114973 ER PT J AU Shen, SJ Hargus, SJ Martin, BM Pohl, LR AF Shen, SJ Hargus, SJ Martin, BM Pohl, LR TI Cytochrome P4502C11 is a target of diclofenac covalent binding in rats SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID ANTIINFLAMMATORY DRUG DICLOFENAC; LIVER PROTEIN ADDUCTS; HEPATOTOXICITY; HEPATITIS; ACTIVATION; MICROSOMES; CD26 AB Diclofenac antiserum was previously developed and used to detect protein adducts of metabolites of dichlofenac in livers of mice and rats. In this study, the antibody has been used to facilitate the purification of a major 51 kDa microsomal adduct of diclofenac from the liver microsomes of male rats that were treated with diclofenac. The adduct was identified as male-specific cytochrome P4502C11 based on its N-terminal amino acid sequence, reaction with a cytochrome P4502C11 antibody, and by its absence from liver microsomes of diclofenac-treated female rats. When diclofenac was incubated with liver microsomes of control rats in the presence of NADPH, only the 51 kDa adduct was produced. The formation of the adduct was inhibited by a cytochrome P4502C11 monoclonal antibody, but not by reduced glutathione or N-alpha-acety-L-lysine. No adduct was detected when diclofenac was incubated with liver microsomes from female rats. Moreover, adduct formation in vivo appeared to lead to a 72% decrease in the activity of cytochrome P4502C11. The results indicate that cytochrome P4502C11 metabolizes diclofenac into a highly reactive product that covalently binds to this enzyme before it can diffuse away and react with other proteins. C1 NIMH,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. RP Shen, SJ (reprint author), NHLBI,MOL & CELLULAR TOXICOL SECT,NIH,BLDG 10,ROOM 8N110,BETHESDA,MD 20892, USA. NR 28 TC 34 Z9 34 U1 0 U2 0 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 APR PY 1997 VL 10 IS 4 BP 420 EP 423 DI 10.1021/tx960167z PG 4 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA WU385 UT WOS:A1997WU38500011 PM 9114979 ER PT J AU Stoller, JK Buist, AS Burrows, B Crystal, RG Fallat, RJ McCarthy, K Schluchter, MD Soskel, NT Zhang, R Bengali, Z Deshler, J Vreim, CE Rothgeb, A Wu, M Snider, GL Detre, K Reynolds, HY Tockman, MS Wittes, J Cohen, A Gadek, JE Rousell, RH Schwartz, RS Turino, GM Brantly, ML Hurd, S Williams, GW Ajamoughli, R Beck, GJ Connelly, RP Dobish, B Goormastic, M Leatherman, J McMahan, J Midcalf, V Moore, B Sartori, P Sherer, SG Swinderman, D Tuason, M Wiedemann, HP Dobish, ME Petty, TL Hildesheim, J Rundquist, B Sandhaus, RA Bell, CW Berend, J Burry, CA Irvine, K Krantz, D Lewis, S Ravikrishnan, KP Begle, R Cameron, B Cotton, S Seidman, J Sherman, S True, M Weinberger, S Armstrong, K Johnston, R Rosenberg, M LaRock, JB Moriyama, L Willard, K Arroliga, AC Meeker, DP Cassidy, E Golish, JA Hutchins, L Laskowski, D Mehta, A Pagliaccio, L Pillar, R Rhodes, G Scott, J Soentjen, L Ryan, WJ Johnson, K Loftin, JP Kotch, A Clark, T Epstein, PE DelBuono, P Sandblom, RE Collar, L Curtis, M DeMaine, JB Melson, B Eichenhorn, MS Beauchamp, R Hupfer, S Lukaszek, C Mackewich, R Wilson, C Breite, WM McMahan, JP DeAtley, R Mylet, D Williams, T WebbJohnson, D Corbett, J Judd, L McManus, D Pierce, J Krowka, MJ Awan, Z Fehrenkamp, R Madden, M Schultz, K Wheatley, N Prakash, UBS Nesler, D Scott, L Scanlon, P Staats, B Viggiano, R Strange, C Baumann, M Burns, B Judson, M Oser, R Youmans, M Killian, DN Demicco, W Golden, L Hess, SA Hitchcock, R Raymond, G Moss, J Barnes, P Czerski, D Healy, J Jolley, C McElvaney, NG Robinson, W Taylor, G Meth, BM Holden, D Ashburn, RW Crowder, G Dolensky, R Hamilton, C Jones, S Forrester, J Sarlin, RF Sen, RP Shelton, B Schuler, B Tyler, M Walsh, TE Zarate, J Wewers, M Drake, J James, B Swank, B Barker, AF DSilva, R Oveson, L Winther, L Sheehan, WC Aisenberg, RM Chadbourne, L Demers, P Little, P Mucciardi, N OliveraWilliams, D Sheehan, A Eden, E Klugh, T Parmar, SI Middleton, ML Montague, D Klink, M Beeler, EP Boyer, B Cline, M Gordon, D Cross, CE Booth, JA Chan, A Fekete, R Kemnitz, H Volz, W Tierney, DF Ezell, L Haugh, J Shapiro, B Clausen, JL Borders, J Dent, C Fonzi, C Ford, R King, SJ Lopez, C Wilson, J Buchmayer, J Anderson, M Bitterman, P Dosland, B Edin, C Harmon, K Hertz, M Krause, S Lindquist, P LovenBell, M Plooster, K Rennard, SI Cheney, R Cirian, D Diamond, J Epperson, K Fogleman, R Houchins, J Jones, K McGranaghan, S Pignotti, T Pursel, T Robbins, RA Donohue, JF Davis, L Hohneker, KW Hornaday, B Mascrella, J Sobol, L Turpin, S Hyde, RW Lynch, R Spohn, B Grisham, C Jones, C Patrick, T Stocks, JM Blevins, WJ Fields, S Hinojosa, J Waldrop, D Wilson, E Kanner, RE Campbell, EJ Behnke, J Pope, K Thelander, C Gross, N King, F Waters, I MacNeill, L Nelson, P Horowitz, M Franklin, B Jenkerson, M Pierce, JA Silverman, E Story, N Wade, M Wilson, P AF Stoller, JK Buist, AS Burrows, B Crystal, RG Fallat, RJ McCarthy, K Schluchter, MD Soskel, NT Zhang, R Bengali, Z Deshler, J Vreim, CE Rothgeb, A Wu, M Snider, GL Detre, K Reynolds, HY Tockman, MS Wittes, J Cohen, A Gadek, JE Rousell, RH Schwartz, RS Turino, GM Brantly, ML Hurd, S Williams, GW Ajamoughli, R Beck, GJ Connelly, RP Dobish, B Goormastic, M Leatherman, J McMahan, J Midcalf, V Moore, B Sartori, P Sherer, SG Swinderman, D Tuason, M Wiedemann, HP Dobish, ME Petty, TL Hildesheim, J Rundquist, B Sandhaus, RA Bell, CW Berend, J Burry, CA Irvine, K Krantz, D Lewis, S Ravikrishnan, KP Begle, R Cameron, B Cotton, S Seidman, J Sherman, S True, M Weinberger, S Armstrong, K Johnston, R Rosenberg, M LaRock, JB Moriyama, L Willard, K Arroliga, AC Meeker, DP Cassidy, E Golish, JA Hutchins, L Laskowski, D Mehta, A Pagliaccio, L Pillar, R Rhodes, G Scott, J Soentjen, L Ryan, WJ Johnson, K Loftin, JP Kotch, A Clark, T Epstein, PE DelBuono, P Sandblom, RE Collar, L Curtis, M DeMaine, JB Melson, B Eichenhorn, MS Beauchamp, R Hupfer, S Lukaszek, C Mackewich, R Wilson, C Breite, WM McMahan, JP DeAtley, R Mylet, D Williams, T WebbJohnson, D Corbett, J Judd, L McManus, D Pierce, J Krowka, MJ Awan, Z Fehrenkamp, R Madden, M Schultz, K Wheatley, N Prakash, UBS Nesler, D Scott, L Scanlon, P Staats, B Viggiano, R Strange, C Baumann, M Burns, B Judson, M Oser, R Youmans, M Killian, DN Demicco, W Golden, L Hess, SA Hitchcock, R Raymond, G Moss, J Barnes, P Czerski, D Healy, J Jolley, C McElvaney, NG Robinson, W Taylor, G Meth, BM Holden, D Ashburn, RW Crowder, G Dolensky, R Hamilton, C Jones, S Forrester, J Sarlin, RF Sen, RP Shelton, B Schuler, B Tyler, M Walsh, TE Zarate, J Wewers, M Drake, J James, B Swank, B Barker, AF DSilva, R Oveson, L Winther, L Sheehan, WC Aisenberg, RM Chadbourne, L Demers, P Little, P Mucciardi, N OliveraWilliams, D Sheehan, A Eden, E Klugh, T Parmar, SI Middleton, ML Montague, D Klink, M Beeler, EP Boyer, B Cline, M Gordon, D Cross, CE Booth, JA Chan, A Fekete, R Kemnitz, H Volz, W Tierney, DF Ezell, L Haugh, J Shapiro, B Clausen, JL Borders, J Dent, C Fonzi, C Ford, R King, SJ Lopez, C Wilson, J Buchmayer, J Anderson, M Bitterman, P Dosland, B Edin, C Harmon, K Hertz, M Krause, S Lindquist, P LovenBell, M Plooster, K Rennard, SI Cheney, R Cirian, D Diamond, J Epperson, K Fogleman, R Houchins, J Jones, K McGranaghan, S Pignotti, T Pursel, T Robbins, RA Donohue, JF Davis, L Hohneker, KW Hornaday, B Mascrella, J Sobol, L Turpin, S Hyde, RW Lynch, R Spohn, B Grisham, C Jones, C Patrick, T Stocks, JM Blevins, WJ Fields, S Hinojosa, J Waldrop, D Wilson, E Kanner, RE Campbell, EJ Behnke, J Pope, K Thelander, C Gross, N King, F Waters, I MacNeill, L Nelson, P Horowitz, M Franklin, B Jenkerson, M Pierce, JA Silverman, E Story, N Wade, M Wilson, P TI Quality control of spirometry testing in the registry for patients with severe alpha(1)-antitrypsin deficiency SO CHEST LA English DT Article DE acceptability; alpha(1)-antitrypsin deficiency; emphysema; quality control; spirometry ID FORCED EXPIRATORY VOLUME; LUNG-FUNCTION; ALPHA-1-ANTITRYPSIN DEFICIENCY; CRITERIA; POPULATION; ASSOCIATION; VARIABILITY; SURVIVAL; SMOKING; DISEASE AB As part of the multicenter National Heart, Lung, and Blood Institute registry of patients with severe deficiency of alpha(1)-antitrypsin with 1,129 enrollees, this report describes measures undertaken to achieve high-quality FEV1 measurements, the rates of satisfying reproducibility and acceptability criteria, and clinical features of participants unable to achieve reproducible FEV1 values at baseline. Spirograms were performed both before and after an inhaled bronchodilator in enrollees followed up at 37 participating clinical centers. Using a reproducibility criterion of <100 mL or 5% (whichever greater), high reproducibility rates for FEV1 measurements at baseline were observed for both prebronchodilator (95.0% of 1,090 sessions) and postbronchodilator measurements (95.7% of 1,077 sessions). Using the more recently published reproducibility criterion of less than or equal to 200 mL, reproducibility rates were even higher. Eighty-four percent of clinical centers submitted FEV1 values that satisfied reproducibility criteria for at least 90% of spirograms. Also, the mean coefficient of variation for prebronchodilator FEV1 values measured over serial visits separated by up to 9 months was 5.6% for participants with baseline FEV1 55 to 90% predicted. This degree of reproducibility is similar to that observed in the Lung Health Study. Rates of satisfying acceptability criteria for prebronchodilator spirograms were lower, almost universally (98% of tests) due to failure to achieve end-of-test criteria (which usually required 15 s of expiration in this population with mean FEV1 = 42.6 +/- 29.6% [SD] predicted). Multivariate logistic regression models show that clinical correlates of failure to achieve reproducible prebronchodilator FEV1 efforts include symptoms of chronic wheeze, chronic cough, and chronic phlegm, and the degree of airflow obstruction. We conclude that highly reproducible FEV1 measurements are achievable in a population with severe airflow obstruction despite the additional challenges posed by testing in multiple centers on a variety of spirometers. Furthermore, the difficulty of satisfying end-of-test criteria in a large cohort with severe airflow obstruction did not preclude achieving high rates of reproducibility for FEV1 measurements. Finally, our study confirms prior observations that failure to achieve reproducible efforts is associated with the presence of pulmonary symptoms and the degree of airflow obstruction. Thus, excluding patients with nonreproducible FEV1 efforts from epidemiologic studies would bias results by including only healthier participants. C1 CLEVELAND CLIN FDN, DEPT BIOSTAT & EPIDEMIOL, CLEVELAND, OH 44195 USA. OREGON HLTH SCI UNIV, DEPT PHYSIOL, PORTLAND, OR 97201 USA. UNIV ARIZONA, RESP SCI CTR, TUCSON, AZ USA. CORNELL UNIV, NEW YORK HOSP, DIV PULM & CRIT CARE MED, MED CTR, ITHACA, NY 14853 USA. CALIF PACIFIC MED CTR, DEPT PULM MED, SAN FRANCISCO, CA USA. UNIV TENNESSEE, DEPT MED, DIV PULM & CRIT CARE MED, MEMPHIS, TN 38104 USA. NICHHD, HUMAN GENET BRANCH, NIH, BETHESDA, MD 20892 USA. ARAPAHOE PULM CONSULTANTS, DENVER, CO USA. WILLIAM BEAUMONT HOSP, ROYAL OAK, MI 48072 USA. BETH ISRAEL HOSP, BOSTON, MA 02215 USA. DALLAS PULM ASSOCIATES, DALLAS, TX USA. DANBURY HOSP, DANBURY, CT USA. UNIV PENN, GRAD HOSP, PHILADELPHIA, PA 19104 USA. GRP HLTH COOPERAT PUGET SOUND, REDMOND, WA USA. HENRY FORD HOSP, DETROIT, MI 48202 USA. INDIANA UNIV, MED CTR, INDIANAPOLIS, IN USA. LAHEY CLIN MED CTR, BURLINGTON, MA 01803 USA. MAYO CLIN JACKSONVILLE, JACKSONVILLE, FL 32224 USA. MAYO CLIN & MAYO FDN, ROCHESTER, MN 55905 USA. MED UNIV S CAROLINA, CHARLESTON, SC 29425 USA. MERCY HOSP, PORTLAND, ME USA. NHLBI, BETHESDA, MD 20892 USA. NATL NAVAL MED CTR, BETHESDA, MD USA. OHIO STATE UNIV, COLUMBUS, OH 43210 USA. PULM CARE PC, FALL RIVER, MA USA. ST LUKES ROOSEVELT HOSP, NEW YORK, NY 10025 USA. UNIV CALIF DAVIS, SACRAMENTO, CA 95817 USA. UNIV CALIF LOS ANGELES, LOS ANGELES, CA 90024 USA. UNIV CALIF SAN DIEGO, MED CTR, SAN DIEGO, CA 92103 USA. UNIV IOWA, IOWA CITY, IA USA. UNIV MINNESOTA HOSP & CLIN, MINNEAPOLIS, MN 55455 USA. UNIV NEBRASKA, MED CTR, OMAHA, NE USA. UNIV N CAROLINA, CHAPEL HILL, NC USA. UNIV ROCHESTER, MED CTR, ROCHESTER, NY 14642 USA. UNIV TENNESSEE, MEMPHIS, TN USA. UNIV TEXAS, CTR HLTH, TYLER, TX 75710 USA. UNIV UTAH, HLTH SCI CTR, SALT LAKE CITY, UT USA. EDWARD HINES JR VET ADM HOSP, HINES, IL 60141 USA. VICTORIA GEN HOSP, VICTORIA, BC, CANADA. WASHINGTON UNIV, MED CTR, ST LOUIS, MO USA. RP Stoller, JK (reprint author), CLEVELAND CLIN FDN, DEPT PULM & CRIT CARE MED, DESK A-90, 9500 EUCLID AVE, CLEVELAND, OH 44195 USA. RI McElvaney, Noel/A-6809-2010 FU NHLBI NIH HHS [N0-HR-86036] NR 31 TC 26 Z9 26 U1 1 U2 10 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD APR PY 1997 VL 111 IS 4 BP 899 EP 909 DI 10.1378/chest.111.4.899 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA WT736 UT WOS:A1997WT73600016 PM 9106567 ER PT J AU Giedd, JN AF Giedd, JN TI Normal development SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID HUMAN CORPUS-CALLOSUM; DEFICIT-HYPERACTIVITY DISORDER; MAGNETIC-RESONANCE IMAGES; SEXUAL DIMORPHISM; TOURETTES-SYNDROME; HUMAN-BRAIN; MORPHOMETRIC ANALYSIS; QUANTITATIVE MORPHOLOGY; MONOZYGOTIC TWINS; INFANTILE-AUTISM AB Interpretation of subtle neuroanatomic differences in clinical populations is illuminated by knowledge of normal brain development. Although total cerebral volume is surprisingly stable from 4 to 18 years of age, various subcomponents of the brain undergo marked and sex-specific developmental changes. These sexually dimorphic patterns of normal brain development may interact with genetic or environmental factors to account for the noted sex differences in age of onset, prevalence, and symptomatology in nearly all neuropsychiatric disorders of childhood onset. High variability of brain structure sizes during development calls for large sample longitudinal study designs. RP Giedd, JN (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,10 CTR DR MSC 1600,BETHESDA,MD 20892, USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 102 TC 9 Z9 9 U1 5 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD APR PY 1997 VL 6 IS 2 BP 265 EP & PG 20 WC Psychiatry SC Psychiatry GA WX109 UT WOS:A1997WX10900004 ER PT J AU Castellanos, FX AF Castellanos, FX TI Neuroimaging of attention-deficit hyperactivity disorder SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID CEREBRAL GLUCOSE-METABOLISM; CHRONIC-SCHIZOPHRENIC PATIENTS; LINKING BASAL GANGLIA; HUMAN-BRAIN; CORPUS-CALLOSUM; QUANTITATIVE MORPHOLOGY; MORPHOMETRIC ANALYSIS; STRUCTURAL ABNORMALITIES; VENTRICULAR ENLARGEMENT; VOLUME ASYMMETRIES AB Neuroimaging in attention-deficit hyperactivity disorder (ADHD) has advanced to the degree that it can now be characterized as scientific enquiry, as it is now possible to formulate explicit falsifiable hypotheses about individual brain regions and circuits. Although methodologic problems remain, there is increasing agreement on the role of the prefrontal-striatal-thalamo-cortical circuit in ADHD, with a preponderance of the evidence suggesting that the right-sided circuit is primary, at least at the level of the basal ganglia. This convergence is all the more remarkable given the many obstacles that have needed to be overcome, chief among them the pleiotropic nature of the disorder. An emphasis on subtyping patient populations by comorbidity, age, and sex, and eventually by meaningful biologic variables such as relevant genotypes, will be crucial in sorting out which other regions are intrinsically related to ADHD, and which are associated with comorbid conditions. RP Castellanos, FX (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,10 CTR DR,ROOM 6N240,BETHESDA,MD 20892, USA. NR 95 TC 18 Z9 18 U1 2 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD APR PY 1997 VL 6 IS 2 BP 383 EP & PG 31 WC Psychiatry SC Psychiatry GA WX109 UT WOS:A1997WX10900010 ER PT J AU Zametkin, A Liotta, W AF Zametkin, A Liotta, W TI The future of brain imaging in child psychiatry SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID MAGNETIC-RESONANCE SPECTROSCOPY; POSITRON EMISSION TOMOGRAPHY; METABOLISM; HYPERACTIVITY AB Neuroimaging has developed rapidly in the past several decades. Understanding of past as well as current techniques in child and adolescent neuroimaging provides insight into possible future advances in the field. Considerations of problems and limitations of the current technology help to define the directions of future developments. This field displays great potential as we strive to decipher the complexities of the human brain. C1 NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. RP Zametkin, A (reprint author), NIMH,OFF CLIN DIRECTOR,BLDG 10,ROOM 4N317,10 CTR DR MSC 1384,BETHESDA,MD 20892, USA. NR 28 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD APR PY 1997 VL 6 IS 2 BP 447 EP & PG 15 WC Psychiatry SC Psychiatry GA WX109 UT WOS:A1997WX10900013 ER PT J AU Pascualvaca, DM Anthony, BJ Arnold, LE Rebok, GW Ahearn, MB Kellam, SG Mirsky, AF AF Pascualvaca, DM Anthony, BJ Arnold, LE Rebok, GW Ahearn, MB Kellam, SG Mirsky, AF TI Attention performance in an epidemiological sample of urban children: The role of gender and verbal intelligence SO CHILD NEUROPSYCHOLOGY LA English DT Article ID CARD SORTING TEST; SEX-DIFFERENCES; HYPERACTIVITY; VIGILANCE; DISORDER; ACHIEVEMENT; INDEXES; GIRLS; MOTOR; RISK AB We administered a comprehensive attentional battery to an epidemiologically defined sample of 435 first-and second-grade children to assess the influence of gender and verbal intelligence on attention. The battery included three versions of the continuous performance test (CPT), two digit cancellation tasks, three subtests from the WISC-R, and the Wisconsin Card Sorting Test. The results indicated that both gender and intelligence had an impact on attentional performance. Girls performed better than boys; they made fewer errors an the CPT and obtained higher scores on the digit cancellation task and the Coding subtest of the WISC-R. Children with higher verbal intelligence also performed better on the attentional tests, but this advantage was not observed across measures or levels of performance. For example, children with limited verbal skills performed significantly worse than their peers only in measures with high processing demands (the degraded CPT and the distraction version of the digit cancellation task). C1 NIMH, SECT CLIN & EXPTL NEUROPSYCHOL, PSYCHOL & PSYCHOPATHOL LAB, BETHESDA, MD 20892 USA. UNIV MARYLAND, SCH MED, DEPT PSYCHIAT, BALTIMORE, MD 21201 USA. NIMH, CHILD & ADOLESCENT DISORDERS RES BRANCH, BETHESDA, MD USA. JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, PREVENT RES CTR, DEPT MENTAL HYG, BALTIMORE, MD 21218 USA. NR 68 TC 28 Z9 29 U1 4 U2 6 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0929-7049 EI 1744-4136 J9 CHILD NEUROPSYCHOL JI Child Neuropsychol. PD APR PY 1997 VL 3 IS 1 BP 13 EP 27 DI 10.1080/09297049708401365 PG 15 WC Clinical Neurology SC Neurosciences & Neurology GA XE553 UT WOS:A1997XE55300002 ER PT J AU Rebok, GW Smith, CB Pascualvaca, DM Mirsky, AF Anthony, BJ Kellam, SG AF Rebok, GW Smith, CB Pascualvaca, DM Mirsky, AF Anthony, BJ Kellam, SG TI Developmental changes in attentional performance in urban children from eight to thirteen years SO CHILD NEUROPSYCHOLOGY LA English DT Article ID SUSTAINED ATTENTION; HUMAN-BRAIN; PSYCHIATRIC STATUS; HYPERACTIVE BOYS; NORMATIVE DATA; VIGILANCE; ADOLESCENCE; MATURATION; MEMORY AB In an earlier study of an epidemiological sample of 435 urban 8-year-old children, factor analytically-derived components of attention, as assessed by neuropsychological tests, were identified and were found to be significantly related to adaptive functioning. In this study we followed that cohort longitudinally and assessed developmental changes in specific aspects of attentional function into early adolescence. Significant reductions in omission errors and improvements in reaction times were found from ages 8 to 13 years on different versions of the Continuous Performance Task, a measure of sustained attention, with the effects varying by task difficulty level and subjects' gender. Significant improvements across age also were found on measures of the ability to focus attention and execute a response, shift attentional focus, and encode information in memory. In general, the most rapid changes in attention occurred between ages 8 to 10 years with more gradual changes occurring between ages 10 to 13. The results highlight the importance of developmental epidemiological approaches for assessing and predicting the normal evolution of attentional function in school-aged children. C1 NIMH, PSYCHOL & PSYCHOPATHOL LAB, SECT CLIN & EXPTL NEUROPSYCHOL, BETHESDA, MD USA. UNIV MARYLAND, SCH MED, DEPT PSYCHIAT, BALTIMORE, MD 21201 USA. RP Rebok, GW (reprint author), JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, DEPT MENTAL HYG, PREVENT RES CTR, 624 N BROADWAY, BALTIMORE, MD 21205 USA. NR 53 TC 59 Z9 61 U1 0 U2 5 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0929-7049 EI 1744-4136 J9 CHILD NEUROPSYCHOL JI Child Neuropsychol. PD APR PY 1997 VL 3 IS 1 BP 28 EP 46 DI 10.1080/09297049708401366 PG 19 WC Clinical Neurology SC Neurosciences & Neurology GA XE553 UT WOS:A1997XE55300003 ER PT J AU Moss, RB Nagata, H Goff, J Okubo, K Hausefeld, J Kaliner, MA AF Moss, RB Nagata, H Goff, J Okubo, K Hausefeld, J Kaliner, MA TI Constitutive mRNA and immunoreactivity for IL-2 in human nasal mucosa SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Article DE IL-2; cytokine; nasal mucosa; airway; T cells ID INFLAMMATORY CELLS; INTERLEUKIN-2; LYMPHOKINES; ACTIVATION; RHINITIS; DISEASE; RNA AB Background The nasal mucosa is the initial site in the upper airway of host defence against antigenic challenge in the form of airborne allergens, irritants, toxins and infectious agents, and yet little is known about nasal mucosal cytokine expression and function. We hypothesized that IL-2 might play a role in immunocompetence of the upper airway. Methods IL-2 immunoreactivity was measured by ELISA in nasal secretions and by Western blot. Immunohistochemistry and electron microscopy were performed on turbinated tissue. mRNA for IL-2 was evaluated by RTPCR and Southern hybridization. Results IL-2 immunoreactivity was demonstrated by Western blot and quantitated by an enzyme immunoassay. Immunohistochemical and electron microscopy analysis of turbinate tissue revealed interstitial staining for IL-2, By RTPCR, IL-2 message was evident in 5/5 atopics and 5/5 non-atopics. IL-2 message was expressed in all subjects by Southern hybridization to an internal probe after PCR. Conclusion This study has demonstrated constitutive expression of IL-2 protein and mRNA in the upper airway of healthy individuals. The further characterization of cytokines in the upper airway could provide useful insights into immune regulation at the mucosal level. C1 NIAID,ALLERG DIS SECT,CLIN INVEST LAB,NIH,BETHESDA,MD 20892. GEORGETOWN UNIV,DEPT MICROBIOL,DIV MOL VIROL & IMMUNOL,WASHINGTON,DC 20057. WASHINGTON HOSP CTR,DEPT FACIAL PLAST & RECONSTRUCT SURG,WASHINGTON,DC 20010. WASHINGTON HOSP CTR,INST ASTHMA & ALLERGY,WASHINGTON,DC 20010. NR 20 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0954-7894 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD APR PY 1997 VL 27 IS 4 BP 406 EP 412 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA WW048 UT WOS:A1997WW04800010 PM 9146933 ER PT J AU Chen, CC Meadows, B Regis, J Kalafsky, G Fojo, T Carrasquillo, JA Bates, SE AF Chen, CC Meadows, B Regis, J Kalafsky, G Fojo, T Carrasquillo, JA Bates, SE TI Detection of in vivo P-glycoprotein inhibition by PSC 833 using Tc-99m sestamibi SO CLINICAL CANCER RESEARCH LA English DT Article ID MEDIATED MULTIDRUG-RESISTANCE; PALPABLE BREAST MASSES; SDZ PSC-833; PLASMA-MEMBRANE; HUMAN-TISSUES; CANCER; VINBLASTINE; CYCLOSPORINE; MODULATORS; TRANSPORT AB Tc-99m sestamibi is a substrate of P-glycoprotein (Pgp) that has been proposed for use as a functional imaging agent for the multidrug resistance-1 phenotype, In vitro, retention of sestamibi by cells that overexpress Pgp can be modified by the presence of Pgp antagonists, In a Phase I trial of the Pgp reversal agent PSC 833, we show that the effects of this reversal agent can also be demonstrated in patients, Nine patients with metastatic renal carcinoma were studied three times: at baseline, approximately 1 day after vinblastine infusion, and while on PSC 833, One patient with metastatic adrenocortical cancer was also studied, Time activity curves and areas under the curve (AUCs) were obtained for tumor, liver, lung, and myocardium, and organ:heart AUC ratios were generated, With PSC 833, tumor visualization was enhanced, and statistically significant increases were found in AUC ratios for tumor and liver compared to baseline, For the liver, significant differences were also found between the vinblastine versus PSC 833 scans but not between the baseline versus vinblastine scans, This study demonstrates that sestamibi retention by tumor and liver is altered in the presence of the reversal agent PSC 833, presumably reflecting inhibition of Pgp, Thus, sestamibi may be useful in vivo as a means of monitoring the effects of this and other reversal agents on various tumors and normal tissues that express Pgp. C1 NOVARTIS PHARMACEUT CORP,E HANOVER,NJ 07936. NATL CANC INST,MED BRANCH,DEPT CLIN SCI,BETHESDA,MD 20892. RP Chen, CC (reprint author), NATL CANC INST,WARREN G MAGNUSON CLIN CTR,DEPT NUCL MED,NIH,10-1C401,10 CTR DR MSC 1180,BETHESDA,MD 20892, USA. RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 40 TC 94 Z9 96 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR PY 1997 VL 3 IS 4 BP 545 EP 552 PG 8 WC Oncology SC Oncology GA WY369 UT WOS:A1997WY36900008 PM 9815718 ER PT J AU Shiao, YH Chen, VW Lehmann, HP Wu, XC Correa, P AF Shiao, YH Chen, VW Lehmann, HP Wu, XC Correa, P TI Patterns of DNA ploidy and S-phase fraction associated with breast cancer survival in blacks and whites SO CLINICAL CANCER RESEARCH LA English DT Article ID FLOW CYTOMETRIC ANALYSIS; CELL-CYCLE ANALYSIS; PROGNOSTIC-SIGNIFICANCE; CARCINOMA; WOMEN AB A significant survival difference between black and white breast cancer patients has been observed in the United States, Evaluation of the prognostic value of DNA ploidy and S-phase fraction (SPF) in black and white breast cancer patients may contribute to our understanding of the mechanisms of racial disparity in survival, A sample of 98 patients (50 blacks and 48 whites) who participated in the Black/White Cancer Survival Study was selected for DNA flow cytometry analysis, Patients were followed between 4.5 and 6.5 years, The impacts of DNA ploidy and SPF on breast cancer survival were examined, Kaplan-Meier survival curves, log rank statistics, and Cox proportional hazards regression were used for survival analyses, Black patients were more likely than white patients to have tumors with high SPF (P < 0.05), but there was no difference in DNA ploidy (P = 0.79), Because there were significant interactions of both DNA ploidy and SPF with race, survival was examined separately for blacks and whites. Significantly poorer survival was observed for white patients with class A ploidy (hypodiploidy, hypotetraploidy, and hypertetraploidy; P = 0.001) and with high SPF (P = 0.025), The elevated hazard ratios remained significant after adjusting for age and stage, Further adjustment for adjuvant therapy and histopathological characteristics of tumor reduced the hazard ratios of SPF to a nonsignificant level, No significant associations were found between survival and DNA ploidy or SPF among blacks. DNA ploidy and SPF are prognostic factors for breast cancer survival in white patients but not in blacks, This may have clinical implication in breast cancer management. C1 LOUISIANA STATE UNIV, MED CTR, DEPT PATHOL, NEW ORLEANS, LA 70112 USA. NCI, FREDERICK CANC RES & DEV CTR, COMPARAT CARCINOGENESIS LAB, NIH, FREDERICK, MD 21702 USA. FU NCI NIH HHS [N01-CN-45175] NR 31 TC 15 Z9 15 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR PY 1997 VL 3 IS 4 BP 587 EP 592 PG 6 WC Oncology SC Oncology GA WY369 UT WOS:A1997WY36900014 PM 9815724 ER PT J AU Sampson, M Ruddel, M Albright, S Elin, RJ AF Sampson, M Ruddel, M Albright, S Elin, RJ TI Positive interference in lithium determinations from clot activator in collection container SO CLINICAL CHEMISTRY LA English DT Article DE analytical error; electrolytes; ion-selective electrodes ID QUALITY AB We describe positive interference with the ion-selective electrode determination of lithium (Lytening 2Z analyzer; Dade) when blood is collected in a 10-mL, plain red-top plastic Vacutainer Plus Tube(R) (Becton Dickinson) containing a silica clot activator and silicone surfactant (prod. no. 36-7820). We evaluated both the original tube (blue-labeled) and a new tube formulated to contain less silicone surfactant (striped-labeled). We determined that the interference is from either the silica clot activator or the silicone surfactant used to fix the silica to the tube and is inversely related to the volume of blood in the tube. Long-term intermittent exposure of the Li ion-selective electrode to the silica clot activator or surfactant results in decreased Li values-in terms of both the positive interference by the silica clot activator or surfactant and the actual Li determinations. Moreover, this long-term interference with the Li ion-selective electrode for patients' specimens is undetected by the Dade control material (QCLytes). RP Sampson, M (reprint author), NIH,CLIN CHEM SERV,DEPT CLIN PATHOL,WARREN G MAGNUSON CLIN CTR,BLDG 10,RM 2C-407,10 CTR DR,BETHESDA,MD 20892, USA. NR 6 TC 16 Z9 18 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD APR PY 1997 VL 43 IS 4 BP 675 EP 679 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA WR521 UT WOS:A1997WR52100020 PM 9105272 ER PT J AU Whitcup, SM Kozhich, AT Lobanoff, M Wolitzky, BA Chan, CC AF Whitcup, SM Kozhich, AT Lobanoff, M Wolitzky, BA Chan, CC TI Blocking both E-selectin and P-selectin inhibits endotoxin-induced leukocyte infiltration into the eye SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article ID INDUCED UVEITIS; ADHESION MOLECULE-1; MONOCLONAL-ANTIBODIES; ENDOTHELIAL-CELLS; DEFICIENT MICE; LUNG INJURY; NEUTROPHILS; LYMPHOCYTES; EXPRESSION; INFLAMMATION AB The initial contact between leukocytes and the vascular endothelium at sites of inflammation is mediated by selectins. The purpose of this study was to investigate the role of the two selectins expressed on the vascular endothelium, E-selectin and P-selectin, in the pathogenesis of endotoxin-induced uveitis. Endotoxin-induced uveitis was produced in female C3H/HeN mice using Salmonella typhimurium endotoxin injected into one hind footpad. At the time of endotoxin injection mice were treated with an intraperitoneal injection of a monoclonal antibody against E-selectin or P-selectin, a combination of both anti-selectin antibodies, or isotype matched control antibodies. In a second set of experiments, antibody treatment was administered 6 hr after endotoxin injection, when inflammatory cells are already entering the eye. Ocular inflammation was graded histologically by a masked observer. When administered at the time of endotoxin injection, anti-P selectin antibody decreased ocular inflammation by 37% compared to control animals (P = 0.05). There was no statistical decrease in ocular inflammation in animals treated with anti-E-selectin antibody. The combination of anti-P-selectin and anti-E-selectin antibodies decreased infiltrating inflammatory cells by 61% (P < 0.01). When treatment was delayed until 6 hr after endotoxin injection, the combination of anti-P selectin and anti-E-selectin antibodies again decreased ocular inflammation by 60% (P < 0.01). Immunohistochemical staining showed decreased ICAM-1 expression in the eyes of animals treated with the combination of anti-P- and anti-E-selectin antibodies. Blocking both P-selectin and E-selectin resulted in a significant decrease in endotoxin-induced intraocular inflammation. (C) 1997 Academic Press. C1 HOFFMANN LA ROCHE INC,ROCHE RES CTR,NUTLEY,NJ 07110. RP Whitcup, SM (reprint author), NEI,NIH,BETHESDA,MD 20892, USA. NR 29 TC 27 Z9 27 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD APR PY 1997 VL 83 IS 1 BP 45 EP 52 DI 10.1006/clin.1996.4324 PG 8 WC Immunology; Pathology SC Immunology; Pathology GA WP273 UT WOS:A1997WP27300012 PM 9073535 ER PT J AU Weissman, D Fauci, AS AF Weissman, D Fauci, AS TI Role of dendritic cells in immunopathogenesis of human immunodeficiency virus infection SO CLINICAL MICROBIOLOGY REVIEWS LA English DT Review ID EPIDERMAL LANGERHANS CELLS; CD4+ T-CELLS; ANTIGEN-PRESENTING CELLS; PERIPHERAL-BLOOD; HIV-INFECTION; IN-VITRO; ACCESSORY CELLS; HIV-1-INFECTED INDIVIDUALS; SEROPOSITIVE PATIENTS; PRODUCTIVE INFECTION AB The role of dendritic cells (DC) in the pathogenesis of human immunodeficiency virus' (HN) disease has been a subject of considerable interest for several yeats. initial studies focused on the infection, dysfunction, and depletion of DC in HIV-infected individuals. More recent studies have begun to identify the functional role of DC in the initiation and propagation of viral replication in T cells in HIV-infected individuals. This review discusses recent data regarding the role of DC in HN disease with the aim of delineating basic immunopathogenic principles of infection and the development of therapeutic strategies. RP Weissman, D (reprint author), NIAID, IMMUNOREGULAT LAB,NIH,BLDG 10,RM 6A02,10 CTR DR, MSC 1576, BETHESDA, MD 20892 USA. NR 160 TC 40 Z9 42 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0893-8512 EI 1098-6618 J9 CLIN MICROBIOL REV JI Clin. Microbiol. Rev. PD APR PY 1997 VL 10 IS 2 BP 358 EP + PG 0 WC Microbiology SC Microbiology GA WT191 UT WOS:A1997WT19100009 PM 9105759 ER PT J AU Rudorfer, MV Potter, WZ AF Rudorfer, MV Potter, WZ TI The role of metabolites of antidepressants in the treatment of depression SO CNS DRUGS LA English DT Review ID MONOAMINE-OXIDASE INHIBITORS; SEROTONIN REUPTAKE INHIBITOR; MUSCARINIC ACETYLCHOLINE-RECEPTORS; SPARTEINE OXIDATION POLYMORPHISM; JAPANESE PSYCHIATRIC POPULATION; 2ND GENERATION ANTIDEPRESSANTS; TRICYCLIC ANTI-DEPRESSANTS; IMPAIRED RENAL-FUNCTION; HUMAN-BREAST MILK; PLASMA-CONCENTRATIONS AB Recognition of the role of active metabolites in mediating therapeutic and/or adverse effects of many antidepressants is an important part of understanding the mechanisms of action of these medications, While virtually all antidepressants except lithium undergo extensive hepatic metabolism, the profile of activity of the resulting breakdown products varies considerably. The metabolites of some antidepressants share the primary biochemical actions of their parent compounds and appear to contribute to the therapeutic efficacy of those medications. Examples of this are the tricyclic antidepressant (TCA) nortriptyline, the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI) fluoxetine and the serotonin-noradrenaline (norepinephrine) reuptake inhibitor venlafaxine. Less commonly, the activity of the primary metabolite may differ from that of the parent drug. An example is clomipramine, This drug is a potent serotonin reuptake blocking TCA, but its demethyl-metabolites are noradrenaline reuptake inhibitors. On the other had, a number of effective antidepressants, including most af the SSRIs other than fluoxetine, lack active metabolites. On the negative side, antidepressant metabolites may add to the adverse effect burden presented by their drugs of origin. At sufficiently high doses, the amphetamines resulting from the metabolism of some monoamine oxidase inhibitors, e.g., selegiline (deprenyl), may directly produce toxicity from the pharmacodynamic interaction with the parent antidepressant. While hydroxy-nortriptyline produces lesser anticholinergic effects than its parent compound, this metabolite may block the therapeutic action of nortriptyline when present in high concentrations. Excessive plasma concentrations of the major metabolite of amfebutamone (bupropion) have been associated with nonresponse and clinical worsening in some patients. Amfebutamone also illustrates the importance of pharmacokinetic factors in determining the magnitude of the influence of metabolites on antidepressant action. Active metabolites that have long elimination half-lives may predominate over the parent compound in plasma and CSF, exerting considerable clinical impact. With several of the newer drugs, notably amfebutamone, venlafaxine and nefazodone, the presence of active metabolites with half-lives approaching 1 day suggests that once-daily administration may be sufficient. The formation of most antidepressant metabolites is under strong genetic control and the metabolites themselves often exert effects on hepatic enzyme systems. This can lend to the possibility of drug-drug interactions. A key example is norfluoxetine, which is associated with potent inhibition of the cytochrome P450 isozyme 2D6 (and, consequently, reduced metabolism of drugs such as TCAs). This effect lasts for weeks even after fluoxetine discontinuation, due to the fact that norfluoxetine has a half-life of up to 2 weeks. The clearance of most antidepressant metabolites is ultimately dependent on climination by the kidney. Therefore, these substances tend to accumulate in states of reduced renal function, including normal aging. The relative increase in TCA hydroxy-metabolite concentrations in the elderly may contribute to the cardiovascular and other toxicities of these antidepressants in this vulnerable patient population. Attention to the existence and implications of active metabolites from the earliest stages of antidepressant drug development may help optimise the benefit: risk ratio of this valuable class of psychotropic medications. RP Rudorfer, MV (reprint author), NIMH,CLIN TREATMENT RES BRANCH,5600 FISHERS LANE,ROOM 18-105,ROCKVILLE,MD 20857, USA. NR 275 TC 36 Z9 37 U1 3 U2 15 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PD APR PY 1997 VL 7 IS 4 BP 273 EP 312 DI 10.2165/00023210-199707040-00003 PG 40 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA WT927 UT WOS:A1997WT92700003 PM 27520753 ER PT J AU OReilly, AW Painter, KM Bornstein, MH AF OReilly, AW Painter, KM Bornstein, MH TI Relations between language and symbolic gesture development in early childhood SO COGNITIVE DEVELOPMENT LA English DT Article ID 2ND YEAR; IMAGINED OBJECTS; PLAY; COMPREHENSION; PANTOMIME; APHASIA; MOTHER; REPRESENTATION; RECOGNITION; BEHAVIOR AB Language development is thought to be associated with other domains of mental activity that require representational capacity, like symbolic gesture. Study 1 explores associations between multiple measures of language and gesture across the third and fourth years of life. Results indicate stability in language, partial stability in gesture, and concurrent and longitudinal associations between language and gesture. Study 2 further explores language-symbolic gesture relations by measuring more finely which aspects of language relate to the symbolic representation of actions with objects and by exploring associations between symbolic gesture and a performance (nonverbal) measure of general intellectual ability. C1 NICHHD,BETHESDA,MD. RP OReilly, AW (reprint author), W VIRGINIA UNIV,DEPT PSYCHOL,POB 6040,MORGANTOWN,WV 26506, USA. NR 38 TC 14 Z9 15 U1 1 U2 2 PU ABLEX PUBL CORP PI GREENWICH PA 55 OLD POST RD NO.2, PO BOX 5297, GREENWICH, CT 06831-0504 SN 0885-2014 J9 COGNITIVE DEV JI Cogn. Dev. PD APR-JUN PY 1997 VL 12 IS 2 BP 185 EP 197 DI 10.1016/S0885-2014(97)90012-5 PG 13 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA YD355 UT WOS:A1997YD35500002 ER PT J AU ElHachimi, KH Chaunu, MP Cervenakova, L Brown, P Foncin, JF AF ElHachimi, KH Chaunu, MP Cervenakova, L Brown, P Foncin, JF TI Putative neurosurgical transmission of Creutzfeldt-Jakob disease with analysis of donor and recipient: agent strains SO COMPTES RENDUS DE L ACADEMIE DES SCIENCES SERIE III-SCIENCES DE LA VIE-LIFE SCIENCES LA English DT Article DE Creutzfeldt-Jakob disease; iatrogenic transmission; PRNP gene; strain agent; immunohistopathology ID PRION PROTEIN; GROWTH-HORMONE; SCRAPIE; VARIANT AB A woman, aged 59 years, underwent a cortical biopsy that led to the diagnosis of Creutzfeldt-Jakob disease (CJD). A man, aged 46 years, underwent cranial surgery in the same department 3 days later for brain contusion, with an uneventful recovery. Twenty six months later, he developed clinical signs of CJD with a typical EEG pattern. Both cases exhibited features of the 'ataxic' form of the disease with depletion of cerebellar granule cells, without kuru plaques or PrP deposits. PrP deposits were immunohistochemically observed in the cerebrum, spinal cord and peripheral nerve. Molecular genetic analysis performed on brain tissue revealed the codon 129 polymorphism to be Met129Met in the donor and Met129Val in the recipient. The shared 'cerebellar' phenotype and the genotypic discrepancy between the two patients leads us to postulate that the 'cerebellar' agent strain plays a major role in CJD phenotype and transmission. C1 HOP LA PITIE SALPETRIERE,INSERM,U106,F-75651 PARIS 13,FRANCE. CHU REIM,NEUROL SERV,F-51100 REIMS,FRANCE. NIH,CENT NERVOUS SYST STUDIES LAB,BETHESDA,MD 20892. RP ElHachimi, KH (reprint author), HOP LA PITIE SALPETRIERE,EPHE NEUROHISTOL,47 BD HOP,F-75651 PARIS 13,FRANCE. NR 27 TC 14 Z9 14 U1 0 U2 1 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 141 RUE JAVEL, 75747 PARIS, FRANCE SN 0764-4469 J9 CR ACAD SCI III-VIE JI Comptes Rendus Acad. Sci. Ser. III-Sci. Vie-Life Sci. PD APR PY 1997 VL 320 IS 4 BP 319 EP 328 DI 10.1016/S0764-4469(97)82774-6 PG 10 WC Biology; Multidisciplinary Sciences SC Life Sciences & Biomedicine - Other Topics; Science & Technology - Other Topics GA YD028 UT WOS:A1997YD02800006 PM 9183437 ER PT J AU Lewine, RRJ AF Lewine, RRJ TI Clinical assessment and management of severe personality disorders - Links,PS SO CONTEMPORARY PSYCHOLOGY LA English DT Book Review C1 SKYLAND TRAIL,ATLANTA,GA. NIMH,ROCKVILLE,MD 20857. RP Lewine, RRJ (reprint author), EMORY UNIV,SCH MED SCHIZOPHREN DISORDERS PROGRAM,ATLANTA,GA 30322, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0010-7549 J9 CONTEMP PSYCHOL JI Comtemp. Psychol. PD APR PY 1997 VL 42 IS 4 BP 304 EP 305 PG 2 WC Psychology, Multidisciplinary SC Psychology GA WR922 UT WOS:A1997WR92200009 ER PT J AU Brinton, LA Gammon, MD Malone, KE Schoenberg, JB Daling, JR Coates, RJ AF Brinton, LA Gammon, MD Malone, KE Schoenberg, JB Daling, JR Coates, RJ TI Modification of oral contraceptive relationships on breast cancer risk by selected factors among younger women SO CONTRACEPTION LA English DT Article DE breast cancer; oral contraceptives; risk factors; interactions ID ALCOHOL-CONSUMPTION; NULLIPAROUS WOMEN; ABORTION; DISEASE AB In a case-control study of 1647 breast cancer cases and 1501 population controls under 45 years of age, potential modifying effects of other risk factors on the relationship of oral contraceptives to breast cancer were examined. Among the total series of study subjects, the relationship of extended pill usage was greater in non-white than white women. Oral contraceptive associations, however, did not appear to be substantially modified by other risk factors, including parity, body size, or family history of breast cancer (apart from a somewhat enhanced relationship among subjects who reported a sister with breast cancer). Further, oral contraceptive relationships did not vary by a history of benign breast disease, although the majority of subjects began pill usage prior to the development of benign breast disease. Among the women under the age of 35, in whom oral contraceptive relationships were heightened (over a twofold excess risk for use of 5 years or longer), pill relationships were less modified by race than in the total series. Although among these younger subjects there was no effect of pill usage in heavy women, and an enhanced relationship among heavier consumers of alcoholic beverages, these interactive effects were not statistically significant. The findings of this study generally support no substantial variation in oral contraceptive relationships by other breast cancer risk factors, although some further attention might be warranted regarding possible modifying effects of race, body size, type of relative with breast cancer, and alcohol consumption. C1 COLUMBIA UNIV, SCH PUBL HLTH, DIV EPIDEMIOL, NEW YORK, NY 10027 USA. FRED HUTCHINSON CANC RES CTR, SEATTLE, WA 98104 USA. NEW JERSEY STATE DEPT HLTH, SPECIAL EPIDEMIOL PROGRAM, TRENTON, NJ 08625 USA. EMORY UNIV, DEPT EPIDEMIOL, ATLANTA, GA 30322 USA. RP Brinton, LA (reprint author), NCI, ENVIRONM EPIDEMIOL BRANCH, EXECUT PLAZA N, ROOM 443, BETHESDA, MD 20892 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 40 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0010-7824 J9 CONTRACEPTION JI Contraception PD APR PY 1997 VL 55 IS 4 BP 197 EP 203 DI 10.1016/S0010-7824(97)00012-7 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XC512 UT WOS:A1997XC51200001 PM 9179450 ER PT J AU BarditchCrovo, P Witter, F Hamzeh, F McPherson, J Stratton, P Alexander, NJ Trapnell, CB AF BarditchCrovo, P Witter, F Hamzeh, F McPherson, J Stratton, P Alexander, NJ Trapnell, CB TI Quantitation of vaginally administered nonoxynol-9 in premenopausal women SO CONTRACEPTION LA English DT Article DE nonoxynol-9; spermicide; HIV prevention; STD prevention ID CONTRACEPTION AB A feasibility study was performed in 11 healthy nonpregnant premenopausal women to determine a method for collection and recovery of vaginally administered nonoxynol-9. We also determined ii nonoxynol-9 could be quantitated in vaginal lavage fluid obtained 2 h after instillation of a standard precoital dose of a foam formulation of nonoxynol-9. Samples were analyzed in batch using a validated normal phase high-performance liquid chromatography (HPLC) method. Two hours after instillation of one dose of Delfen(R) Contraceptive Foam (100 mg), the quantity of nonoxynol-9 collected ranged from 10.8 to 67.8 mg (mean: 35.4 mg). This corresponds to a recovery of 11-70% of the administered dose. Quantitation of vaginally administered nonoxynol-9 is both practical and feasible. These data represent a critical first step in the evaluation of the safety and effectiveness of nonoxynol-9-containing products in the prevention of sexually transmitted diseases. (C) 1997 Elsevier Science Inc. C1 JOHNS HOPKINS UNIV, SCH MED, DEPT MED, DIV CLIN PHARMACOL, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT OBSTET & GYNECOL, BALTIMORE, MD 21205 USA. NICHHD, CONTRACEPT DEV BRANCH, ROCKVILLE, MD USA. US FDA, CTR DRUG EVALUAT & RES, ROCKVILLE, MD 20857 USA. FU NCRR NIH HHS [RR00722]; PHS HHS [223-93-3011] NR 11 TC 7 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0010-7824 J9 CONTRACEPTION JI Contraception PD APR PY 1997 VL 55 IS 4 BP 261 EP 263 DI 10.1016/S0010-7824(97)00003-6 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA XC512 UT WOS:A1997XC51200010 PM 9179459 ER PT J AU Freedman, LS Gail, MH Green, SB Corle, DK AF Freedman, LS Gail, MH Green, SB Corle, DK TI The efficiency of the matched-pairs design of the Community Intervention Trial for Smoking Cessation (COMMIT) SO CONTROLLED CLINICAL TRIALS LA English DT Article DE group randomization; cluster randomization; behavioral change; smoking cessation; community intervention; matching; relative efficiency ID CARDIOVASCULAR-DISEASE; EDUCATION AB The Community Intervention Trial for Smoking Cessation (COMMIT) was a randomized trial to evaluate the effects of a community-wide smoking cessation intervention design involved 22 pair-matched communities on smoking behavior. The statistical and the randomization of one community in each of the 11 pairs to the intervention with the other community in the pair acting as a comparison. Communities were matched on the basis of their geographical proximity and similarity of demographic composition. In this paper, we use the data on the rates of quitting smoking among cohorts of heavy and light/moderate smokers in each community to estimate the gains in efficiency achieved by the matched-pairs design compared to an unmatched randomized trial. We find evidence of some gain in efficiency, although the data are not extensive enough to give estimates of efficiency gain that have good precision. Published by Elsevier Science Inc. 1997. C1 NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. RP Freedman, LS (reprint author), NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,6130 EXECUT BLVD,MSC 7354,EPN ROOM 344,BETHESDA,MD 20892, USA. NR 12 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD APR PY 1997 VL 18 IS 2 BP 131 EP 139 DI 10.1016/S0197-2456(96)00115-8 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA WV087 UT WOS:A1997WV08700002 PM 9129857 ER PT J AU Eichacker, PQ AF Eichacker, PQ TI Inhaled nitric oxide in adult respiratory distress syndrome: Do we know the risks versus benefits? SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE nitric oxide; adult respiratory distress syndrome; vasodilator; pulmonary circulation ID RIGHT-VENTRICULAR FUNCTION; ACUTE LUNG INJURY; SUPEROXIDE; NO; FAILURE RP Eichacker, PQ (reprint author), NIH,DEPT CRIT CARE MED,CRIT CARE MED SECT,BLDG 10,ROOM 7D-43,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 33 TC 3 Z9 3 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 1997 VL 25 IS 4 BP 563 EP 565 DI 10.1097/00003246-199704000-00002 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA WW930 UT WOS:A1997WW93000002 PM 9142017 ER PT J AU Paterson, CA Zeng, JW Husseini, Z Borchman, D Delamere, NA Garland, D JimenezAsensio, J AF Paterson, CA Zeng, JW Husseini, Z Borchman, D Delamere, NA Garland, D JimenezAsensio, J TI Calcium ATPase activity and membrane structure in clear and cataractous human lenses SO CURRENT EYE RESEARCH LA English DT Article DE calcium ATPase; cataract; epithelium; lens; spectroscopy; human ID RABBIT LENS; BOVINE LENS; TRANSPORT; SIMPLIFICATION; CA-2+-ATPASE; SPECTROSCOPY; CA2+-ATPASE; CELLS; ASSAY; GREEN AB Purpose. Maintenance of calcium homeostasis is imperative for the clarity of the lens. Ca2+-ATPase is essential for the removal of cytosolic calcium, either across the plasma membrane or through intracellular organelles such as the endoplasmic reticulum. In this study, membranes prepared from clear lens epithelium were compared to membranes prepared from cataractous lens epithelium. Methods. Human lens membranes were prepared by a protocol utilizing homogenization and centrifugation. Ca2+-ATPase activity was measured biochemically using Gamma-P-32 labeled ATP. Lipid order was measured using infrared and Raman spectroscopy. Results. Ca2+-ATPase activity was similar in membranes prepared from cataractous lenses that were classified as nuclear subcapsular, nuclear and brunescent cataracts. Ca2+-ATPase activity was approximately 50% less in membranes prepared from cataractous lenses in comparison to clear lenses. Because clear lenses from Indian donors was unavailable, clear human lenses were used as a qualitative control for the measurement for Ca2+-ATPase activity. Lipid order was measured in lens fibers from cataractous and clear lenses from the United States donors. Lipid order increased from 55% in the hydrocarbon chains from clear lens fibers to 84% in cataractous lens fibers. Conclusions. These findings support the hypothesis that membranes are deranged in cataractous tissue, which should lead to altered levels of calcium. C1 UNIV LOUISVILLE, SCH MED, KENTUCKY LIONS EYE RES INST, DEPT OPHTHALMOL & VISUAL SCI, LOUISVILLE, KY 40292 USA. NEI, NIH, BETHESDA, MD 20892 USA. FU NEI NIH HHS [EY06916, EY07975, EY09532] NR 30 TC 46 Z9 49 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0271-3683 EI 1460-2202 J9 CURR EYE RES JI Curr. Eye Res. PD APR PY 1997 VL 16 IS 4 BP 333 EP 338 DI 10.1076/ceyr.16.4.333.10689 PG 6 WC Ophthalmology SC Ophthalmology GA WT731 UT WOS:A1997WT73100008 PM 9134322 ER PT J AU Morrison, DK Cutler, RE AF Morrison, DK Cutler, RE TI The complexity of Raf-1 regulation SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; 14-3-3 PROTEIN; RAS; 14-3-3-PROTEINS; PHOSPHORYLATION; IDENTIFICATION; MEMBRANE; BINDING; CELLS; DEFINITION AB The activation of the serine/threonine kinase Raf-1 is proving to be an intricate multistep process. Recent advances in elucidating how Raf-1 becomes activated in response to signaling events have emphasized the role of phosphorylation and protein interactions in Raf-1 regulation. The picture clearly emerging is that Raf-1 activity can be regulated by multiple mechanisms. RP Morrison, DK (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOL BASIS CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. NR 62 TC 501 Z9 505 U1 2 U2 8 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD APR PY 1997 VL 9 IS 2 BP 174 EP 179 DI 10.1016/S0955-0674(97)80060-9 PG 6 WC Cell Biology SC Cell Biology GA WQ619 UT WOS:A1997WQ61900008 PM 9069260 ER PT J AU Tsukiyama, T Wu, C AF Tsukiyama, T Wu, C TI Chromatin remodeling and transcription SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID DNA-BINDING PROTEIN; YEAST SWI/SNF COMPLEX; CELL-FREE SYSTEM; SACCHAROMYCES-CEREVISIAE; MULTISUBUNIT COMPLEX; HISTONE ACETYLATION; NUCLEOSOME DISRUPTION; NEGATIVE REGULATOR; AMINO-TERMINUS; GENE-PRODUCTS AB Recent advances highlight two important chromatin remodeling systems involved in the transcriptional process. One system includes several members of the evolutionarily conserved SWI2/SNF2 family found in distinct multiprotein complexes with ATP-dependent nucleosome destabilizing activity; the other is the enzymatic system that governs histone acetylation and deacetylation. Identification of the catalytic subunits of these opposing histone-modifying activities reveal conserved proteins defined genetically as transcriptional regulators. C1 NCI,MOL CELL BIOL LAB,NIH,BETHESDA,MD 20892. NR 140 TC 174 Z9 175 U1 0 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD APR PY 1997 VL 7 IS 2 BP 182 EP 191 DI 10.1016/S0959-437X(97)80127-X PG 10 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA WW570 UT WOS:A1997WW57000006 PM 9115421 ER PT J AU Bosserhoff, AK Kondo, S Moser, M Dietz, UH Copeland, NG Gilbert, DJ Jenkins, NA Buettner, R Sandell, LJ AF Bosserhoff, AK Kondo, S Moser, M Dietz, UH Copeland, NG Gilbert, DJ Jenkins, NA Buettner, R Sandell, LJ TI Mouse CD-RAP/MIA gene: Structure, chromosomal localization, and expression in cartilage and chondrosarcoma SO DEVELOPMENTAL DYNAMICS LA English DT Article DE MIA; melanoma; CD-RAP; chondrogenesis; mouse gene ID MESSENGER-RNA; DIFFERENTIAL EXPRESSION; RAT CHONDROSARCOMA; COLLAGEN GENE; PROCOLLAGEN; PROTEIN; IDENTIFICATION; ORGANIZATION; PROPEPTIDE; SEQUENCE AB A cDNA encoding a novel protein has been previously isolated from two independent sources: melanoma cell cultures and chondrocytes. The protein from human melanoma cell lines and tumors is called melanoma inhibitory activity (MIA) (Blesch et al. [1994] Cancer Res. 54:5695-5701) and the protein from primary bovine chondrocytes and cartilaginous tissues is called cartilage-derived retinoic acid-sensitive protein (CD-RAP) (Dietz and Sandell [1996] J. Biol. Chem. 271:3311-3316). In order to investigate the gene regulation and function of CD-RAP/MIA, the mouse gene locus was isolated and analyzed, Developmental expression was determined by in situ hybridization to mouse embryos. Expression was limited to cartilaginous tissues and was initiated with the advent of chondrogenesis, remaining abundant throughout development. The mouse gene was isolated and sequenced from a 129Sv library and sequenced directly from an additional strain, B6C3Fe. The mouse CD-RAP/MIA gene is 1.5 kbp and consists of four exons. The promoter sequence of the gene contains many potential regulatory domains including 8 basic helix-loop-helix protein-binding domains and an AT-rich domain, both motifs shown to be present in the cartilage-specific enhancer of the type II procollagen gene. Other potential cis-acting motifs include binding sites for GATA-1, NF-IL6, PEA3, w-elements, NF kappa B, Zeste and Spl. The gene, called cdrap, was localized to the end of an arm of chromosome 7 at the same site as the transforming growth factor beta 1 (Tgf-beta 1) and the glucose phosphate isomerase 1 (Gpi1) genes. Potential mouse mutants that mapped to the same region of chromosome 7 mere identified. Two of the potential mutants with skeletal phenotypes were sequenced, pudgy (pu) and extra toes with spotting (Xs(J)); however, no mutations were found in the coding sequence. To determine whether CD-RAP/MIA is associated with tumors of cartilage, mRNAs from a variety of rodent tissues and cell lines were screened, Expression was detected in a rodent tumor, the Swarm rat chondrosarcoma and a chondrosarcoma cell line derived from it, but not in other tissues or tumors of non-cartilage origin. Immunolocalization revealed CD-RAP/MIA protein localized in cartilage only, These results show that the normal expression of CD-RAP/MIA is limited to cartilage; however, pathologically, it is expressed both in melanoma and chondrosarcoma. The restricted expression of CD-RAP/MIA may provide an opportunity to monitor cartilage metabolic activity as well as the tumor activity of melanoma and chondrosarcoma. (C) 1997 Wiley-Liss, Inc. C1 UNIV WASHINGTON,DEPT ORTHOPED ORT 112,VA PUGET SOUND HLTH CARE SYST,SEATTLE,WA 98108. UNIV WASHINGTON,DEPT BIOCHEM,VA PUGET SOUND HLTH CARE SYST,SEATTLE,WA 98108. UNIV REGENSBURG,DEPT PATHOL,D-93053 REGENSBURG,GERMANY. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NIAMS NIH HHS [R01AR36994] NR 31 TC 95 Z9 105 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD APR PY 1997 VL 208 IS 4 BP 516 EP 525 DI 10.1002/(SICI)1097-0177(199704)208:4<516::AID-AJA7>3.0.CO;2-L PG 10 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA WQ842 UT WOS:A1997WQ84200007 PM 9097023 ER PT J AU Chai, Y Sasano, Y Bringas, P Mayo, M Kaartinen, V Heisterkamp, N Groffen, J Slavkin, H Shuler, C AF Chai, Y Sasano, Y Bringas, P Mayo, M Kaartinen, V Heisterkamp, N Groffen, J Slavkin, H Shuler, C TI Characterization of the fate of midline epithelial cells during the fusion of mandibular prominences in vivo SO DEVELOPMENTAL DYNAMICS LA English DT Article DE mandible; morphogenesis; medial epithelial cells; TGF-beta 3 null mutation ID MESENCHYMAL TRANSFORMATION; DIFFERENTIAL EXPRESSION; PALATAL DEVELOPMENT; GROWTH-FACTOR; DEATH AB The fusion of the mandibular prominences along the midline is achieved with the absence of medial epithelial cells at the fusion site. Failure of fusion of the mandibular prominences results in median cleft of the lower lip and mandible. Cellular and molecular events controlling mandibular fusion were examined during the fusion process in mouse embryogenesis. Cell lineage analyses at the fusion site revealed that epithelial cells migrated to the surface and oral epithelia. DiI-labeled epithelial cells were not observed within the mandibular mesenchyme at any stage of fusion. Examination of the midline region did not reveal cells with ultrastructural changes characteristic of apoptotic cell death. An increase in lysosomal enzymes in the midline epithelial cells, which would be correlated with programmed cell death, was not observed. Mice lacking TGF-beta 3 did not have cleft mandible, but had clefting of the secondary palate as a feature of null mutation phenotype. We interpret our comparisons between wild type and homozygous TGF-beta 3 (-/-) mice to suggest that different developmental processes control palatal vs. mandibular fusion. We hypothesize that medial epithelial cells at the fusion site of mandibular prominences migrate to the surface epithelium during the fusion process and neither transdifferentiate into mesenchyme nor express apoptosis. (C) 1997 Wiley-Liss, Inc. C1 UNIV SO CALIF,SCH DENT,CTR CRANIOFACIAL MOL BIOL,LOS ANGELES,CA 90033. CHILDRENS HOSP LOS ANGELES,DEPT PATHOL,RES INST,LOS ANGELES,CA 90027. CHILDRENS HOSP LOS ANGELES,DEPT SURG,RES INST,LOS ANGELES,CA 90027. CHILDRENS HOSP LOS ANGELES,DEPT PEDIAT,RES INST,LOS ANGELES,CA 90027. NIAMSD,CRANIOFACIAL DEV SECT,NIH,BETHESDA,MD. OI Kaartinen, Vesa/0000-0002-9432-510X FU NICHD NIH HHS [N01-HD-2-3144]; NIDCR NIH HHS [DE-09165] NR 23 TC 16 Z9 16 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD APR PY 1997 VL 208 IS 4 BP 526 EP 535 DI 10.1002/(SICI)1097-0177(199704)208:4<526::AID-AJA8>3.0.CO;2-K PG 10 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA WQ842 UT WOS:A1997WQ84200008 PM 9097024 ER PT J AU Edelstein, SL Knowler, WC Bain, RP Andres, R BarrettConnor, EL Dowse, GK Haffner, SM Pettitt, DJ Sorkin, JD Muller, DC Collins, VR Hamman, RF AF Edelstein, SL Knowler, WC Bain, RP Andres, R BarrettConnor, EL Dowse, GK Haffner, SM Pettitt, DJ Sorkin, JD Muller, DC Collins, VR Hamman, RF TI Predictors of progression from impaired glucose tolerance to NIDDM - An analysis of six prospective studies SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; 10-YEAR FOLLOW-UP; UNITED-STATES POPULATION; BODY-FAT DISTRIBUTION; PIMA-INDIANS; NATURAL-HISTORY; RISK-FACTORS; MEXICAN-AMERICANS; INSULIN; PREVALENCE AB Risk factors associated with the progression from impaired glucose tolerance (IGT) to NIDDM were examined in data from six prospective studies. IGT and NIDDM were defined in all studies by World Health Organization (WHO) criteria, and baseline risk factors were measured at the time of first recognition of IGT. The studies varied in size from 177 to 693 participants with IGT, and included men and women followed from 2 to 27 years after the recognition of IGT. Across the six studies, the incidence rate of NIDDM was 57.2/1,000 person-years and ranged from 35.8/1,000 to 87.3/1,000 person-years. Although baseline measures of fasting and 2-h postchallenge glucose levels were both positively associated with NIDDM incidence, incidence rates were sharply higher for those in the top quartile of fasting plasma glucose levels, but increased linearly with increasing 2-h postchallenge glucose quartiles. Incidence rates were higher among the Hispanic, Mexican-American, Pima, and Nauruan populations than among Caucasians. The effect of baseline age on NIDDM incidence rates differed among the studies; the rates did not increase or rose only slightly with increasing baseline age in three of the studies and formed an inverted U in three studies. In all studies, estimates of obesity (including BMI, waist-to-hip ratio, and waist circumference) were positively associated with NIDDM incidence. BMI was associated with NIDDM incidence independently of fasting and 2-h post challenge glucose levels in the combined analysis of all six studies and in three cohorts separately, but not in the three studies with the highest NIDDM incidence rates. Sex and family history of diabetes were generally not related to NIDDM progression. This analysis indicates that persons with IGT are at high risk and that further refinement of risk can be made by other simple measurements. The ability to identify persons at high risk of NIDDM should facilitate clinical trials in diabetes prevention. C1 NIDDKD,PHOENIX,AZ. NIA,BALTIMORE,MD 21224. UNIV CALIF SAN DIEGO,DEPT FAMILY & PREVENT MED,LA JOLLA,CA 92093. INT DIABET INST,MELBOURNE,VIC,AUSTRALIA. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV COLORADO,SCH MED,DEPT PREVENT MED & BIOMETR,DENVER,CO. RP Edelstein, SL (reprint author), GEORGE WASHINGTON UNIV,CTR BIOSTAT,6110 EXECUT BLVD,SUITE 750,ROCKVILLE,MD 20852, USA. FU NHLBI NIH HHS [R01 HL036820, HL24799]; NIDDK NIH HHS [DK48489, R01 DK031801, U01 DK048489, U01 DK048489-06] NR 49 TC 389 Z9 408 U1 0 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 1997 VL 46 IS 4 BP 701 EP 710 DI 10.2337/diabetes.46.4.701 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WP644 UT WOS:A1997WP64400023 PM 9075814 ER PT J AU Pan, XR Li, GW Hu, YH Wang, JX Yang, WY An, ZX Hu, ZX Lin, J Xiao, JZ Cao, HB Liu, PA Jiang, XG Jiang, YY Wang, JP Zheng, H Zhang, H Bennett, PH Howard, BV AF Pan, XR Li, GW Hu, YH Wang, JX Yang, WY An, ZX Hu, ZX Lin, J Xiao, JZ Cao, HB Liu, PA Jiang, XG Jiang, YY Wang, JP Zheng, H Zhang, H Bennett, PH Howard, BV TI Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance - The Da Qing IGT and diabetes study SO DIABETES CARE LA English DT Article ID CORONARY HEART-DISEASE; 10-YEAR FOLLOW-UP; PIMA-INDIANS; PHYSICAL EXERCISE; INSULIN ACTION; BEDFORD SURVEY; RISK-FACTORS; PREVALENCE; MELLITUS; OBESITY AB QBJECTIVE - Individuals with impaired glucose tolerance (IGT) have a high risk of developing NIDDM. The purpose of this study was to determine whether diet and exercise interventions in those with IGT may delay the development of NIDDM, i.e., reduce the incidence of NIDDM, and thereby reduce the overall incidence of diabetic complications, such as cardiovascular, renal, and retinal disease, and the excess mortality attributable to these complications. RESEARCH DESIGN AND METHODS - In 1986, 110,660 men and women from 33 health care clinics in the city of Da Qing, China, were screened for IGT and NIDDM. Of these individuals, 577 were classified (using World Health Organization criteria) as having IGT. Subjects were randomized by clinic into a clinical trial, either to a control group or to one of three active treatment groups: diet only, exercise only, or diet plus exercise. Follow-up evaluation examinations were conducted at 2-year intervals over a 6-year period to identify subjects who developed NIDDM. Cox's proportional hazard analysis was used to determine if the incidence of NIDDM varied by treatment assignment. RESULTS - The cumulative incidence of diabetes at 6 years was 67.7% (95% CI, 59.8-75.2) in the control group compared with 43.8% (95% CI, 35.5-52.3) in the diet group, 41.1% (95% CI, 33.4-49.4) in the exercise group, and 46.0% (95% CI, 37.3-54.7) in the diet-plus-exercise group (P < 0.05). When analyzed by clinic, each of the active intervention groups differed significantly from the control clinics (P < 0.05). The relative decrease in rate of development of diabetes in the active treatment groups was similar when subjects were stratified as lean or overweight (BMI < or greater than or equal to 25 kg/m(2)). In a proportional hazards analysis adjusted for differences in baseline BMI and fasting glucose, the diet, exercise, and diet-plus-exercise interventions were associated with 31% (P < 0.03), 46% (P < 0.0005), and 42% (P < 0.005) reductions in risk of developing diabetes, respectively. CONCLUSIONS - Diet and/or exercise interventions led to a significant decrease in the incidence of diabetes over a B-year period among those with IGT. C1 MEDLANT RES INST,WASHINGTON,DC 20010. CHINA JAPAN FRIENDSHIP HOSP,DEPT ENDOCRINOL,BEIJING,PEOPLES R CHINA. CHINA JAPAN FRIENDSHIP HOSP,DEPT NUTR,BEIJING,PEOPLES R CHINA. DA QING HOSP 1,DEPT CARDIOVASC DIS,DA QING,PEOPLES R CHINA. NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,NIH,PHOENIX,AZ. NR 22 TC 2041 Z9 2153 U1 22 U2 134 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 1997 VL 20 IS 4 BP 537 EP 544 DI 10.2337/diacare.20.4.537 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WP645 UT WOS:A1997WP64500018 PM 9096977 ER PT J AU Abati, A Sanford, J Fetsch, P Pass, H AF Abati, A Sanford, J Fetsch, P Pass, H TI Detection of aneuploidy in mesothelioma cell lines by fluorescence in situ hybridization (FISH) SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Letter RP Abati, A (reprint author), NCI,CYTOPATHOL SECT,NIH,BLDG 10,ROOM 2A19,10 CTR DR MSC 1500,BETHESDA,MD 20892, USA. NR 3 TC 2 Z9 2 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. PD APR PY 1997 VL 16 IS 4 BP 375 EP 377 PG 3 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA WW896 UT WOS:A1997WW89600015 PM 9143836 ER PT J AU Chen, LP Buters, JTM Hardwick, JP Tamura, S Penman, BW Gonzalez, FJ Crespi, CL AF Chen, LP Buters, JTM Hardwick, JP Tamura, S Penman, BW Gonzalez, FJ Crespi, CL TI Coexpression of cytochrome P4502A6 and human NADPH-P450 oxidoreductase in the baculovirus system SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID NUCLEAR POLYHEDROSIS-VIRUS; CDNA-DIRECTED EXPRESSION; HUMAN LIVER-MICROSOMES; INSECT CELLS; CATALYTIC PROPERTIES; VECTOR SYSTEM; REDUCTASE; PROMOTERS; ENZYMES; PROTEIN AB Heterologous expression using baculovirus vectors has become a popular method for the production of catalytically active cytochrome P450s (CYPs). We have systematically optimized the multiplicity of infection (MOI) for a coinfection approach for the coexpression of CYP2A6 (viral vector designated v2A6) and NADPH-P450 oxidoreductase (OR; viral vector designated vOR) using Sf9 insect cells. A 3000-fold range of MOI was examined in stationary culture and stirred suspension culture. Surprisingly, our results Indicate that the best CYP2A6 catalytic activity (850-1300 pmol/ min/mg total lysate protein as measured by coumarin 7-hydroxylase activity) was obtained only when using a low MOI of v2A6 (1.5-3 x 10(-2)) and a vOR of 10- to 20-fold less, This activity was similar to 7- to 11-fold higher than the best activity obtained when infecting cells with v2A6 alone. At this level of coinfection, the P450 content ranged from 180 to 250 pmol/mg total lysate protein, and the NADPH cytochrome c reductase activity ranged from 350 to 520 nmol/min/mg total lysate protein. Increasing the MOI of both viruses to 50-fold higher resulted in lower overall activity with the optimum (250 pmol/min/mg total lysate protein) being seen earlier postinfection (60 vs. 72 hr). Increasing the MOI of vOR to levels comparable with those of v2A6, decreased coumarin 7-hydroxylase activity 14-fold. These results suggest that the best CYP2A6 catalytic activity depends on properly posttranslationally modified proteins accumulating in a right ratio as a result of primary, secondary, and possibly tertiary infection of both viruses. These results also suggest that high OR expression results in degradation of P450. C1 NCI,NIH,BETHESDA,MD 20892. NE OHIO UNIV,COLL MED,ROOTSTOWN,OH 44272. RI Buters, Jeroen/G-5070-2011 FU NIEHS NIH HHS [N43-ES-31001] NR 37 TC 30 Z9 30 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD APR PY 1997 VL 25 IS 4 BP 399 EP 405 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WT742 UT WOS:A1997WT74200002 PM 9107537 ER PT J AU Sipe, HJ Corbett, JT Mason, RP AF Sipe, HJ Corbett, JT Mason, RP TI In vitro free radical metabolism of phenolphthalein by peroxidases SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID ELECTRON-SPIN-RESONANCE; HYDROGEN-PEROXIDE; HORSERADISH-PEROXIDASE; BILIARY-EXCRETION; OXIDATION; KINETICS; ACID; LACTOPEROXIDASE; METHEMOGLOBIN; ACETAMINOPHEN AB Phenolphthalein, a widely used laxative, is the active ingredient in more than a dozen commercial nonprescription formulations. Fast-flow EPR studies of the reaction of phenolphthalein with horseradish peroxidase (HRP) and hydrogen peroxide permit the direct detection of two free radicals. One has EPR parameters characteristic of phenoxyl radicals. The other has a broad unresolved spectrum, possibly arising from free radical polymeric products of the initial phenoxyl radical. EPR spin-trapping studies of incubations of phenolphthalein with lactoperoxidase, reduced glutathione (GSH), and hydrogen peroxide with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) demonstrate stimulated production of DMPO/(.)SG compared with an identical incubation lacking phenolphthalein. In the absence of DMPO, measurements with a Clark-type oxygen electrode show that molecular oxygen is consumed by a sequence of reactions initiated by the glutathione thiyl radical. Enhanced production of DMPO superoxide radical adduct is also found in a system of phenolphthalein, NADH, and lactoperoxidase. In this system the phenolphthalein phenoxyl radical abstracts hydrogen from NADH to generate NAD(.), which is nor spin trapped by DMPO, but reacts with molecular oxygen to produce the superoxide radical detected by EPR. In the absence of DMPO, the oxygen consumption is measured using the Clark-type electrode. Production of ascorbate radical anion is also enhanced in a system of phenolphthalein, ascorbic acid, hydrogen peroxide, and lactoperoxidase. Ascorbate inhibits oxygen consumption when phenolphthalein is metabolized in the presence of either glutathione or NADH by reducing radical intermediates to their parent molecules and forming the relatively stable ascorbate anion radical. The detection of enhanced free radical production in these three systems, a consequence of futile metabolism (or redox cycling), suggests that phenolphthalein may be a significant source of oxidative stress in physiological systems, Parallel EPR and oxygen consumption studies with phenolphthalein glucuronide give analogous results, but with lesser enhancement of free radical production. C1 NIEHS,LAB PHARMACOL & CHEM,NIH,RES TRIANGLE PK,NC 27709. NR 50 TC 23 Z9 24 U1 1 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD APR PY 1997 VL 25 IS 4 BP 468 EP 480 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WT742 UT WOS:A1997WT74200012 PM 9107547 ER PT J AU Zhuang, P Toro, C Grafman, J Manganotti, P Leocani, L Hallett, M AF Zhuang, P Toro, C Grafman, J Manganotti, P Leocani, L Hallett, M TI Event-related desynchronization (ERD) in the alpha frequency during development of implicit and explicit learning SO ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE EEG; alpha frequency; event-related desynchronization; implicit learning; explicit learning ID LONG-TERM POTENTIATION; SYNAPTIC PLASTICITY; MOTOR CORTEX; MEMORY; MECHANISMS; MODULATION; BEHAVIOR; AREA; EEG; SYNCHRONIZATION AB To understand the role of the motor cortex in implicit and explicit learning, we studied alpha event-related desynchronization (ERD) while 13 right-handed individuals performed a variation of the serial reaction time task (SRTT). EEG signals were recorded simultaneously from 29 scalp locations and the ERD was computed. During data collection, all subjects developed implicit knowledge, demonstrated by shortening of the response time, and explicit knowledge of the test sequence. The average ERD maps of all 13 subjects demonstrated that during the initial learning, there was a decline in alpha band power that was maximal over the contralateral central region. The ERD reached a transient peak amplitude at a point when the subjects attained full explicit knowledge, and diminished subsequently. The transient peak in ERD was highly significant at C3, These electrophysiologic findings support previous studies which have demonstrated that motor activity changes as behavior changes over the course of learning. (C) 1997 Elsevier Science Ireland Ltd. C1 NINCDS, HUMAN MOTOR CONTROL SECT, MED NEUROL BRANCH, NIH, BETHESDA, MD 20892 USA. NINCDS, COGNIT NEUROSCI SECT, MED NEUROL BRANCH, NIH, BETHESDA, MD 20892 USA. OI Grafman, Jordan H./0000-0001-8645-4457 NR 54 TC 57 Z9 58 U1 0 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0013-4694 J9 ELECTROEN CLIN NEURO JI Electroencephalogr. Clin. Neurophysiol. PD APR PY 1997 VL 102 IS 4 BP 374 EP 381 DI 10.1016/S0013-4694(96)96030-7 PG 8 WC Engineering, Biomedical; Clinical Neurology SC Engineering; Neurosciences & Neurology GA WW672 UT WOS:A1997WW67200015 PM 9146500 ER PT J AU Mercuri, B Wassermann, EM Ikoma, K Samii, A Hallett, M AF Mercuri, B Wassermann, EM Ikoma, K Samii, A Hallett, M TI Effects of transcranial electrical and magnetic stimulation on reciprocal inhibition in the human arm SO ELECTROMYOGRAPHY AND MOTOR CONTROL-ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE transcranial electrical stimulation; transcranial magnetic stimulation; reciprocal inhibition; H-reflex; M-wave; motor evoked potentials ID MOTOR CORTEX STIMULATION; INTACT MAN; DISYNAPTIC INHIBITION; SPINAL MOTONEURONS; HUMAN FOREARM; RESPONSES; MUSCLES; MONKEY; POTENTIALS; REFLEXES AB We studied the effects of transcranial electrical stimulation (TES) and transcranial magnetic stimulation (TMS), delivered at intensities below the threshold for evoking an electromyographic response, on the disynaptic and presynaptic phases of reciprocal inhibition in 8 healthy subjects. After TES, the H-reflex evoked in the flexor carpi radialis (FCR) muscle was strongly facilitated when the cortical stimulus was given 4.0-4.5 ms after the test stimulus (median nerve stimulus). TES reduced the disynaptic phase of reciprocal inhibition most strongly when the cortical stimulus followed the test stimulus by 3.0-3.5 ms. TES also reduced presynaptic inhibition, but with a time course that was identical to that of the facilitation of the uninhibited H-reflex. After subthreshold TMS, the facilitation of the H-reflex showed at least 2 peaks, one occurring when the cortical stimulus was given 2 ms after the test stimulus and the other when the cortical stimulus followed the test stimulus by 0.5 to -1.5 ms. The effects of TMS on the 2 phases of reciprocal inhibition were similar, and in both cases the disinhibitory effects had essentially the same time course as the facilitatory effect of TMS on the uninhibited H-reflex. The different effects of TES on the 2 phases of reciprocal inhibition provide evidence of the presynaptic nature of the second phase. The absence of a difference in the effect of TMS on the 2 phases could be due to the more temporally dispersed descending volley after TMS. (C) 1997 Elsevier Science Ireland Ltd. C1 NINCDS,HUMAN MOTOR CONTROL SECT,MED NEUROL BRANCH,NIH,BETHESDA,MD 20892. RI Ikoma, Katsunori/D-8158-2012 NR 30 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0924-980X J9 ELECTROMYOGR MOTOR C JI Electromyogr. Mot. Control-Electroencephalogr. Clin. Neurophysiol. PD APR PY 1997 VL 105 IS 2 BP 87 EP 93 DI 10.1016/S0924-980X(96)96085-3 PG 7 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA WX416 UT WOS:A1997WX41600001 PM 9152200 ER PT J AU Majumder, S Zhao, ZY Kaneko, K DePamphilis, ML AF Majumder, S Zhao, ZY Kaneko, K DePamphilis, ML TI Developmental acquisition of enhancer function requires a unique coactivator activity SO EMBO JOURNAL LA English DT Article DE coactivators; enhancers; mouse development; transcription; zygotic gene activation ID PREIMPLANTATION MOUSE EMBRYO; RNA-POLYMERASE-II; GENE-EXPRESSION; MIDBLASTULA TRANSITION; HISTONE ACETYLATION; XENOPUS-LAEVIS; MAMMALIAN DEVELOPMENT; CHROMATIN STRUCTURE; ACTIVATION DOMAINS; PROMOTER ACTIVITY AB Enhancers are believed to stimulate promoters by relieving chromatin-mediated repression, However, injection of plasmid-encoded genes into mouse oocytes and embryos revealed that enhancers failed to stimulate promoters prior to formation of a two-cell embryo, even though the promoter was repressed in the maternal nucleus of both oocytes and one-cell embryos, The absence of enhancer function was not due to the absence of a required sequence-specific enhancer activation protein, because enhancer function was not elicited even when these proteins either were provided by an expression vector (GAL4:VP16) or were present as an endogenous transcription;factor (TEF-1) and shown to be active in stimulating promoters, Instead, enhancer function in vivo required a unique coactivator activity in addition to enhancer-specific DNA binding proteins and promoter repression. This coactivator activity first appeared during mouse development in two- to four-cell embryos, concurrent with the major onset of zygotic gene expression, Competition between various enhancers was observed in these embryos, but not competition between enhancers and promoters, and competition between enhancers was absent in one-cell embryos, Moreover, enhancer function in oocytes could be partially restored by pre-injecting mRNA from cells in which enhancers were active, the same mRNA did not affect enhancer function in two- to four-cell embryos. C1 NICHHD,NIH,BETHESDA,MD 20892. RP Majumder, S (reprint author), UNIV TEXAS,MD ANDERSON CANC CTR,1515 HOLCOMBE BLVD,BOX 100,HOUSTON,TX 77030, USA. FU NIGMS NIH HHS [GM53454-01A1] NR 61 TC 42 Z9 42 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD APR 1 PY 1997 VL 16 IS 7 BP 1721 EP 1731 DI 10.1093/emboj/16.7.1721 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA XA869 UT WOS:A1997XA86900025 PM 9130716 ER PT J AU Ikuyama, S Ohe, K Takayanagi, R Kohn, LD Nawata, H AF Ikuyama, S Ohe, K Takayanagi, R Kohn, LD Nawata, H TI Cloning and characterization of the 4.2 kb region of the rat thyrotropin receptor promoter SO ENDOCRINE JOURNAL LA English DT Article DE TSH receptor; gene; promoter; TTF-1 ID TRANSCRIPTION FACTOR-I; RESPONSE ELEMENT; BINDING-PROTEINS; GENE-EXPRESSION; THYROID-CELLS; TTF-1; CDNA AB We previously identified an approximately 200 bp ''minimal promoter'' of the rat TSH receptor (TSHR) gene which is essential for the promoter activity. In the present study, we have cloned and characterized an upstream region of the TSHR promoter to disclose additional functional element(s). We screened a rat genomic library and obtained a DNA fragment which contained a 4.2 kb 5'-flanking region. This fragment was 2.5 kb longer than that we previously studied (1.7 kb). To assess the promoter activity, chimeric plasmids containing the 4.2 kb promoter and its 5'-deletions ligated to a chloramphenicol acetyltransferase gene were transfected into thyroid and non-thyroid cells. These plasmids expressed significant promoter activity in FRTL-5 and FRT thyroid cells, but not in BRL liver cells. The strongest promoter activity was expressed by the -199 bp promoter, and the longer promoter expressed rather decreased activity. Co-expression of thyroid transcription factor-1 (TTF-1) increased the activity of the promoter region from -3187 to -199 bp, which encompassed one or two TTF-1 binding sites we previously identified, but not the -4206 bp promoter. In addition, FRTL-5 stable transfectants each having a chimeric construct were cultured in the presence or absence of TSH. All transfectants expressed higher promoter activity in the absence of TSH than in the presence of TSH, in particular, the -3187 bp plasmid expressed significantly higher activity by comparison to the -2617 and -4206 bp constructs. This result indicates that the region between -3187 and -2617 bp may contribute to TSH/cAMP-induced suppression and also suggests that the region between -4206 and -3187 bp involves the element(s) for constitutive suppression of the promoter activity. These results not only suggest that the 4.2 kb upstream region of the TSHR gene possibly contains some elements for the regulation of the gene expression, but also emphasize the importance of the minimal promoter region which we previously identified for the efficient expression of the gene. C1 NIDDKD,CELL REGULAT SECT,METAB DIS BRANCH,NIH,BETHESDA,MD 20892. RP Ikuyama, S (reprint author), KYUSHU UNIV,DEPT INTERNAL MED 3,FAC MED,HIGASHI KU,3-1-1 MAIDASHI,FUKUOKA 81282,JAPAN. NR 30 TC 5 Z9 5 U1 0 U2 0 PU JAPAN ENDOCRINE SOCIETY PI TOKYO PA C/O DEPT VETERINARY PHYSIOL, VET MED SCI, UNIV TOKYO, 1-1-1 YAYOI, BUNKYO-KU, TOKYO 113, JAPAN SN 0918-8959 J9 ENDOCR J JI Endocr. J. PD APR PY 1997 VL 44 IS 2 BP 247 EP 256 DI 10.1507/endocrj.44.247 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WU699 UT WOS:A1997WU69900006 PM 9228460 ER PT J AU Parrizas, M Gazit, A Levitzki, A Wertheimer, E LeRoith, D AF Parrizas, M Gazit, A Levitzki, A Wertheimer, E LeRoith, D TI Specific inhibition of insulin-like growth factor-1 and insulin receptor tyrosine kinase activity and biological function by tyrphostins SO ENDOCRINOLOGY LA English DT Article ID FACTOR-I RECEPTOR; APOPTOSIS; PROLIFERATION; FAMILY; DOMAIN AB A series of the synthetic protein tyrosine kinase inhibitors known as tyrphostins were studied for their effect on insulin-like growth factor-1 and insulin-stimulated cellular proliferation on NIH-3T3 fibroblasts overexpressing either receptor, as well as for their ability to inhibit ligand-stimulated receptor autophosphorylation and tyrosine kinase activity toward exogenous substrates. Several of the tyrphostins tested demonstrated a dramatic effect by inhibiting hormone-stimulated cell proliferation, with IC(50)s in the submicromolar range, while being unable to block serum-stimulated cell proliferation. The tyrphostins also inhibited receptor autophosphorylation and tyrosine kinase activity, with a higher IC50, in the micromolar range. Most of the tyrphostins tested presented no clear preference for either receptor, although two of them (AG1024 and AG1034) showed significantly lower IC(50)s for IGF-1 than for insulin receptors. These results suggest that, in spite of the high homology of the kinase regions of both receptors, it could be possible to design and synthesize small molecules capable of discriminating between them. The syn thesis of such specific inhibitors could be an excellent tool to establish the precise signalling mechanisms that distinguish between the different effects of these two hormones. C1 NIDDK,DIABET BRANCH,NIH,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,ALEXANDER SILBERMAN INST LIFE SCI,DEPT BIOL CHEM,IL-91904 JERUSALEM,ISRAEL. TEL AVIV UNIV,SACKLER SCH MED,DEPT PATHOL,IL-69978 RAMAT AVIV,ISRAEL. NR 29 TC 164 Z9 166 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 1997 VL 138 IS 4 BP 1427 EP 1433 DI 10.1210/en.138.4.1427 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WP335 UT WOS:A1997WP33500010 PM 9075698 ER PT J AU Rao, K Paik, WY Zheng, LX Jobin, RM Tomic, M Jiang, H Nakanishi, S Stojilkovic, SS AF Rao, K Paik, WY Zheng, LX Jobin, RM Tomic, M Jiang, H Nakanishi, S Stojilkovic, SS TI Wortmannin-sensitive and -insensitive steps in calcium-controlled exocytosis in pituitary gonadotrophs: Evidence that myosin light chain kinase mediates calcium-dependent and wortmannin-sensitive gonadotropin secretion SO ENDOCRINOLOGY LA English DT Article ID ADRENAL CHROMAFFIN CELLS; BASOPHILIC RBL-2H3 CELLS; PROTEIN-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; HORMONE RELEASE; PHOSPHOLIPASE-C; INHIBITION; RECEPTOR; ACTIVATION; PHOSPHORYLATION AB In cultured rat pituitary cells, increases in the cytosolic calcium concentration ([Ca2+](i)) and LW release are induced by activation of GnRH receptors as well as by nonreceptor-mediated stimuli. Treatment of pituitary cells with the myosin light chain kinase (MLCK) inhibitor, wortmannin, attenuated GnRH-induced LH release. Wortmannin also reduced the LW responses to nonreceptor-mediated elevation of [Ca2+](i) by ionomycin and activation of voltage-sensitive Ca2+ channels by Bay K 8644 or high K+, as well as Ca2+-induced LH release in permeabilized pituitary cells. The [Ca2+](i) responses to these stimuli were unaltered in wortmannin-treated pituitary cells, indicating that this compound inhibits a Ca2+-dependent step in exocytosis without affecting Ca2+ signaling. In perifused pituitary cells, the GnRH-induced early spike phase of LH release was not affected by wortmannin, whereas the subsequent plateau phase was almost completely inhibited. No significant changes in GnRH-induced phospholipase D activity and diacylglycerol production were observed in wortmannin-treated pituitary cells during the sustained phase of agonist stimulation. Wortmannin also had no effect on LH responses to the protein kinase C activator, phorbol 12-myristate 13-acetate, further indicating that the attenuation of agonist-induced LH release is not related to inhibition of the diacylglycerol/protein kinase C pathway. In addition, agonist-induced LH release was attenuated by two other MLCK inhibitors, MS-347a and KT5926. These data suggest that MLCK mediates the downstream effects of Ca2+ on exocytosis, an action supported by the finding of wortmannin-sensitive phosphorylation of a 20-kDa protein in pituitary cells and alpha T3-1 gonadotrophs treated with GnRH, K+, and Bay K 8644. This protein was coprecipitated from pituitary extracts with a specific antibody to nonmuscle myosin IIB and comigrated with 20-kDa smooth muscle myosin light chain on SDS-PAGE. These results demonstrate that Ca2+ controls exocytosis through an initial wortmannin-insensitive step and a sustained wortmannin-sensitive step and suggest that the latter event in the cascade of cellular responses is dependent on phosphorylation of nonmuscle myosin IIB light chain by MLCK. C1 NICHHD, ENDOCRINOL & REPROD RES BRANCH, NIH, BETHESDA, MD 20892 USA. KYOWA HAKKO KOGYO CO LTD, TOKYO RES LABS, TOKYO, JAPAN. RI Tomic, Melanija/C-3371-2016 NR 42 TC 26 Z9 26 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 1997 VL 138 IS 4 BP 1440 EP 1449 DI 10.1210/en.138.4.1440 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WP335 UT WOS:A1997WP33500012 PM 9075700 ER PT J AU Zhu, XG McPhie, P Cheng, SY AF Zhu, XG McPhie, P Cheng, SY TI Differential sensitivity of thyroid hormone receptor isoform homodimers and mutant heterodimers to hormone-induced dissociation from deoxyribonucleic acid: Its role in dominant negative SO ENDOCRINOLOGY LA English DT Article ID GENERALIZED RESISTANCE; NUCLEAR RECEPTOR; BINDING-CAPACITY; BETA; DNA; MECHANISMS; EXPRESSION AB General resistance to thyroid hormone is an inheritable disease with resistance of peripheral tissues to elevated levels of thyroid hormone. Genetic studies have shown that it is due to interference in the functions of wild-type thyroid hormone nuclear receptors (wTRs) via the dominant negative effect of mutant TRs (mTRs). The present study compared the heterodimerization of the two TR isoforms, TR beta 1 and TR alpha 1, with mutant TRs to understand if mTRs had isoform-dependent dominant negative action. Using electrophoresis gel mobility shift assay, we have demonstrated that mutant PV, S, ED, and OK form heterodimers with wTR alpha 1 and Delta TR beta 1 (in which the A/B domain of wTR beta 1 has been deleted), on the F2-thyroid hormone response element (TRE). In the presence of T-3, both home- and heterodimer complexes are dissociated in a T-3 concentration dependent manner. The ED(50) for Delta TR beta 1 homodimers was 3-fold higher than that of wTR alpha 1 homodimers. ED(50)s for Delta TR beta 1/mTR heterodimers were 10- to 40-fold higher than the corresponding wTR alpha 1/mTR heterodimers. Mutant ED and OK homodimers were only partially dissociated at the highest T-3 concentrations used (100 nm), whereas no dissociation could be detected for PV and S homodimers, indicating differential sensitivity of the FB-bound TR dimers to the T-3-induced dissociation. We presented a model that indicates the dissociation of any particular TR dimer from FZ is determined bg competition of T-3 for both of its constituent TRs. By transfection assays, we showed that the potency of the dominant negative action of PV on TR alpha 1 and TR beta 1 inversely correlated with the sensitivity of the appropriate mTR/wTR heterodimer to T-3-induced dissociation from F2. The differential dominant negative action of mutants on the two TR isoforms could play an important role in the heterogeneity of tissue-specific manifestations in patients with resistance to thyroid hormone. C1 NCI, MOL BIOL LAB, BETHESDA, MD 20892 USA. NCI, DIV BASIC SCI, BETHESDA, MD 20892 USA. NIDDKD, BIOCHEM PHARMACOL LAB, NIH, BETHESDA, MD 20892 USA. NR 24 TC 10 Z9 11 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 1997 VL 138 IS 4 BP 1456 EP 1463 DI 10.1210/en.138.4.1456 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WP335 UT WOS:A1997WP33500014 PM 9075702 ER PT J AU Ramamoorthy, K Wang, F Chen, IC Norris, JD McDonnell, DP Leonard, LS Gaido, KW Bocchinfuso, WP Korach, KS Safe, S AF Ramamoorthy, K Wang, F Chen, IC Norris, JD McDonnell, DP Leonard, LS Gaido, KW Bocchinfuso, WP Korach, KS Safe, S TI Estrogenic activity of a dieldrin/toxaphene mixture in the mouse uterus, MCF-7 human breast cancer cells, and yeast-based estrogen receptor assays: No apparent synergism SO ENDOCRINOLOGY LA English DT Article ID E-SCREEN ASSAY; POLYCHLORINATED-BIPHENYLS; ORGANOCHLORINE COMPOUNDS; PESTICIDES; DIOXINS; BINDING; GENE AB The estrogenic activity of dieldrin, toxaphene, and an equimolar mixture of both compounds (dieldrin/toxaphene) was investigated in the 21-day-old B6C3F1 mouse uterus, MCF-7 human breast cancer cells, and in yeast-based reporter gene assays. Treatment of the animals with 17 beta-estradiol (E(2)) (0.0053 kg/day x3) resulted in a 3.1-, 4.8-, and 7.8-fold increase in uterine wet weight, peroxidase activity, and progesterone receptor binding, respectively. In contrast, treatment with 2.5, 15 and 60 mu mol/Kg (x3) doses of toxaphene, dieldrin, or dieldrin/toxaphene (equimolar) did not significantly induce a dose dependent increase in ally of the E(2)-induced responses. The organochlorine pesticides alone and the binary mixture did not bind to the mouse uterine estrogen receptor (En) in a competitive binding assay using [H-3]E(2) as the radioligand. In parallel studies, estrogenic a activities were determined in MCF-7 cells by using a cell proliferation assay and by determining induction of chloramphenicol acetyl transferase (CAT) activity in MCF-7 cells transiently transfected with plasmids containing estrogen-responsive 5'-promotel regions from the rat creatine kinase B and human cathepsin D genes. E, caused a 24-fold increase in CAT activity in MCF-7 cells transiently transfected with creatine kinase B and a 3.8-fold increase in cells transiently transfected with the human cathepsin D construct. Treatment of MCF-7 cells with dieldrin, toxaphene, or an equimolar mixture of dieldrin plus toxaphene 10(-8)-10(-5) M) did not significantly induce cell proliferation or CAT activity in the transient transfection experiment with both plasmids. The relative competitive binding of the organochlorine pesticides was determined by incubating MCF-7 cells with 10(-9) M [3H]E, in the presence or absence of 2 x 10(-7) M unlabeled E(2) ito determine nonspecific binding), toxaphene (10(-5) M), dieldrin (10(-5) M), and equimolar concentrations of the dieldrin plus toxaphene mixture (10(-5) M). The binding observed for [H-3]E(2) in the whole cell extracts was displaced by unlabeled E,, whereas the organochlorine pesticides acid binary mixture exhibited minimal to nondetectable competitive binding activity. E(2) caused a 5000-fold induction of P-galactosidase (p-gal) activity in yeast transformed with the human ER and a double estrogen responsive element upstream of the P-gal reporter gene. Treatment with 10(-6)-10(-4) M chlordane, dicldrin, toxaphene, or an equimolar mixture of dieldrin/toxaphene did not induce activity, whereas 10(-4) M endosulfan caused a 2000-fold increase in beta-gal activity. Diethylstilbcstrol caused a 20-fold increase in activity in yeast transformed with the mouse ER and a single estrogen responsive element upstream of the beta-gal reporter gene. Dieldrin, chlordane, toxaphene, and endosulfan induced a 1.5- to 4-fold increase in actitity at a concentration of 2.5x10(-5) M. Synergistic transactivation was not observed for any equimolar binary mixture of the pesticides at concentrations of either 2.5 x 10(-5) M or 2.5 x 10(-4) M. The results of this study demonstrate that for several estrogen-responsive assays in the mouse uterus, MCF-7 human breast cancer cells, and yeast-based reporter gene assays, the activities of both dieldrin and toxaphene were minimal, and no synergistic interactions were observed with a binary mixture of the two compounds. C1 TEXAS A&M UNIV, COLLEGE STN, TX 77843 USA. DUKE UNIV, SCH MED, DEPT PHARMACOL, DURHAM, NC 27709 USA. CHEM IND INST TOXICOL, RES TRIANGLE PK, NC 27709 USA. NIEHS, REPROD & DEV TOXICOL LAB, RES TRIANGLE PK, NC 27709 USA. OI Korach, Kenneth/0000-0002-7765-418X FU NIDDK NIH HHS [DK-48807]; NIEHS NIH HHS [ES-04917] NR 36 TC 106 Z9 106 U1 0 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 1997 VL 138 IS 4 BP 1520 EP 1527 DI 10.1210/en.138.4.1520 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WP335 UT WOS:A1997WP33500023 PM 9075711 ER PT J AU Patibandla, SA Seetharamaiah, GS Dallas, JS Thotakura, NR Peake, RL Prabhakar, BS AF Patibandla, SA Seetharamaiah, GS Dallas, JS Thotakura, NR Peake, RL Prabhakar, BS TI Differential reactivities of recombinant glycosylated ectodomains of mouse and human thyrotropin receptors with patient autoantibodies SO ENDOCRINOLOGY LA English DT Article ID GRAVES-DISEASE; TSH RECEPTOR; EXTRACELLULAR DOMAIN; MICE; INDUCTION; BINDING; IMMUNOGLOBULINS; ANTIBODIES; HYPERTHYROXINEMIA; IDENTIFICATION AB We expressed the extracellular domain of the mouse TSH receptor (mET-gp) using the baculovirus expression system. The recombinant protein was identified as mET-gp by immunoblotting and N-terminal amino acid sequencing. Carbohydrate analysis of the recombinant protein showed that the protein is glycosylated. Experimental antibodies raised against the extracellular domain of the human TSHr (ETSHr) were assayed for reactivity against mET-gp and glycosylated human ETSHr (ETSHr-gp) in an ELISA and found to be comparable. Similarly, both mET-gp and ETSHr-gp proteins neutralized the TSH binding inhibitory immunoglobulin (TBII) activity of rabbit anti-ET-SHr antibodies in a RRA. However, when these proteins were compared for their ability to neutralize TBII and blocking activities (TSBAb) of IgG from patients with thyroid autoimmune disorders, only ETSHr-gp was able to neutralize these activities. In contrast, mET-gp partially neutralized, whereas ETSHr-gp completely neutralized the stimulatory (TSAb) activities of IgG from patients. Analyses of reactivities of these two proteins against a panel of antipeptide and monoclonal antibodies and their protein sequences showed differences in some specific epitopes. These data showed that in spite of significant homology between the two proteins, they exhibit specific epitope differences that are sufficient to cause divergence in their ability to react with patient autoantibodies to TSHr. This suggests that the two proteins might differ in their three-dimensional structure. C1 UNIV TEXAS, MED BRANCH, DEPT MICROBIOL & IMMUNOL, GALVESTON, TX 77555 USA. UNIV TEXAS, MED BRANCH, DEPT PEDIAT, GALVESTON, TX 77555 USA. UNIV TEXAS, MED BRANCH, DEPT INTERNAL MED, GALVESTON, TX 77555 USA. NIDDKD, MOL & CELLULAR ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. FU NIDDK NIH HHS [DK-44972, DK-47417] NR 26 TC 18 Z9 18 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 1997 VL 138 IS 4 BP 1559 EP 1566 DI 10.1210/en.138.4.1559 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WP335 UT WOS:A1997WP33500028 PM 9075716 ER PT J AU Khanum, A Buczko, E Dufau, ML AF Khanum, A Buczko, E Dufau, ML TI Essential role of adenosine triphosphate in activation of 17 beta-hydroxysteroid dehydrogenase in the rat Leydig cell SO ENDOCRINOLOGY LA English DT Article ID DEPENDENT PROTEIN-KINASE; AMINO-ACID SEQUENCE; GLUCOSE-TRANSPORT; SELECTIVE INHIBITOR; ADENYLATE-CYCLASE; POTENT INHIBITORS; FORSKOLIN; PHOSPHORYLATION; EXPRESSION; PURIFICATION AB The forskolin-induced steroidogenic block of testosterone production residing beyond pregnenolone synthesis in rat Leydig cells was localized to the level of the 17 beta-hydroxgsteroid dehydrogenase (17 beta HSD) reaction in this study. The use of forskolin analogs that discriminate between the diterpene's inhibitory effect on the glucose transporter(s) (1,9-dideoxyforskolin) and its activation of adenylate cyclase (6-aminoethyl carbamyl forskolin) revealed that the block is related to inhibition of glucose transporter(s). 1,9-Dideoxyforskolin, but not 6-aminoethyl carbamyl forskolin, caused a significant inhibition of basal and hCG-stimulated testosterone production with accumulation of androstenedione. Glucose-deficient media produced the same metabolic block in the absence of forskolin, with a significant reduction in 17 beta HSD activity and increases in the apparent K-m for androstenedione. In contrast, metabolic steps before testosterone formation were not affected. Glucose-induced 17 beta HSD activation was mimicked by the addition of ATP or GTP in glucose-deficient media, but not by nonhydrolyzable triphosphate analogs or NADPH. A decrease in 17 beta HSD activity caused by KT-5720, a specific inhibitor of protein kinase A and the calmodulin antagonist W-7, indicates that the ATP requirement mag be related to the participation of protein kinases in the activation of 17 beta HSD. ATP levels derived from alternative (nonglycolytic) pathways are adequate to support basal and hormone-stimulated enzymatic activities in the metabolism of cholesterol to androstenedione. However, the integrity of the glucose transport system with subsequent ATP generation is required for activation of 17 beta HSD in the final step of androgen biosynthesis. In conclusion, the conversion of androstenedione to testosterone requires the contribution of the glycolytic pathway to meet ATP requirements for 17 beta HSD activity. C1 NICHHD,SECT MOL ENDOCRINOL,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. NR 43 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 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 1997 VL 138 IS 4 BP 1612 EP 1620 DI 10.1210/en.138.4.1612 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WP335 UT WOS:A1997WP33500034 PM 9075722 ER PT J AU Lee, CY Wu, HB Suh, DS Rechler, MM AF Lee, CY Wu, HB Suh, DS Rechler, MM TI Insulin-like growth factor-I (IGF-I) concentration in 150-kilodalton complexes containing human IGF-binding protein-3 (hIGFBP-3) after intravenous injection of adult rats with hIGFBP-3 SO ENDOCRINOLOGY LA English DT Article ID ACID-LABILE SUBUNIT; FACTOR (IGF)-BINDING PROTEIN-3; HUMAN-SERUM; THYROTROPIN; CLEARANCE; PITUITARY AB After iv injection into adult rats, human insulin-like growth factor-binding protein-3 (hIGFBP-3) forms 150-kDa complexes with excess endogenous rat acid-labile subunit (ALS) within 2 min (Lewitt et ai., 1993, Endocrinology 133:1797). Because their previous in vitro studies indicated that hIGFBP-3 only bound to ALS in the presence of IG F-I, and because little free TGF-I is present in plasma, the authors postulated that IGF-I bad been mobilized to the circulation to saturate the 150-kDa hIGFBP-3 complexes. We examined this hypothesis by determining whether the hIGFBP-3 that appears in 150-kDa complexes 2 min after iv injection is accompanied by an increase in IGF-I. Within 2 min, some of the injected hIGFBP-3 (similar to 30% as much as endogenous intact rat IGFBP-3) is present in complexes that are cleared slowly from the circulation and presumed to be 150-kDa complexes. Gel filtration and immunoprecipitation studies performed on blood collected 2 min after injection confirmed that the injected hIGFBP-3 (46-82% as much as rat IGFBP-3) was associated with ALS in 150-kDa complexes. The formation of 150-kDa complexes containing hIGFBP-3 was not accompanied by a corresponding change in the IGF-I content (determined by RIA) of whole serum or 150-kDa serum fractions, suggesting that the hIGFBP-3 had rapidly associated with rALS in vivo without mobilizing IGF-I. Surprisingly, however, hIGFBP-3 was cleared much more rapidly from 150-kDa complexes formed after injection of hIGFBP-3 than after injection of hIGFBP-3:IGF-I complexes, suggesting that the complexes observed after hIGFBP-3 injection might not have formed in vivo. In fact, 150-kDa complexes formed to a similar extent when hIGFBP-3 was added ex vivo to blood collected from rats that had not received hIGFBP-3. We conclude that hIGFBP-3 can rapidly associate with rALS to form 150-kDa complexes in vivo without the mobilization of IGF-I. Because 150-kDa complexes also are formed ex vivo, however, we are unable to resolve whether the complexes that formed in vivo formed as binary or ternary complexes. C1 NIH,NIDDKD,GROWTH & DEV SECT,MOL & CELLULAR ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 21 TC 7 Z9 7 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 1997 VL 138 IS 4 BP 1649 EP 1657 DI 10.1210/en.138.4.1649 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA WP335 UT WOS:A1997WP33500039 PM 9075727 ER PT J AU Davis, DL Sieber, SM AF Davis, DL Sieber, SM TI Hormones, hormone metabolism, environment, and breast cancer: A Workshop of the National Action Plan on Breast Cancer's Etiology Working Group SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 NATL CANC INST,BETHESDA,MD. RP Davis, DL (reprint author), WORLD RESOURCES INST,1709 NEW YORK AVE NW,WASHINGTON,DC 20006, USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 1997 VL 105 SU 3 BP 557 EP 557 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA XB828 UT WOS:A1997XB82800001 PM 9167994 ER PT J AU Dorgan, JF Longcope, C Stephenson, HE Falk, RT Miller, R Franz, C Kahle, L Campbell, WS Tangrea, JA Schatzkin, A AF Dorgan, JF Longcope, C Stephenson, HE Falk, RT Miller, R Franz, C Kahle, L Campbell, WS Tangrea, JA Schatzkin, A TI Serum sex hormone levels are related to breast cancer risk in postmenopausal women SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Workshop on Hormones, Hormone Metabolism, Environment, and Breast Cancer CY SEP 28-29, 1995 CL NEW ORLEANS, LA DE breast neoplasms; androgens; estrogens; epidemiology AB We conducted a nested case-control study to prospectively evaluate the relationship of serum estrogens and androgens to risk of breast cancer in postmenopausal women. From 1977 to 1987, 3375 postmenopausal women free of cancer and not taking replacement estrogens donated blood to the Breast Cancer Serum Bank in Columbia, Missouri. Of these, 72 were subsequently diagnosed with breast cancer. For each case, two controls matched on age and date and rime of day of blood collection were selected using incidence density matching. The median age of subjects at blood collection was 62 years; the time from blood collection to diagnosis ranged from less than 1 to 9.5 years with a median of 2.9 years. Risk of breast cancer was positively and significantly associated with serum levels of estrogens and androgens. Compared to women in the lowest quartile, those in the highest quartile for non-sex hormone-binding globulin (non-SHBG) bound (bioavailable) estradiol had a relative risk of 5.2 (95% confidence interval [CI] = 1.5-18.5) and those in the highest quartile for testosterone had a relative risk of 6.2 (95% CI = 2.0-19.0). Our results lend considerable support to the hypothesis that serum concentrations of estrogens and androgens are related to the subsequent diagnosis of breast cancer in postmenopausal women. C1 UNIV MASSACHUSETTS,SCH MED,DEPT OBSTET & GYNECOL,WORCESTER,MA. UNIV MISSOURI,HLTH SCI CTR,DEPT SURG,COLUMBIA,MO. NCI,DIV CANC ETIOL & GENET,BETHESDA,MD 20892. ELLIS FISCHEL CANC CTR,CANC SCREENING SERV,COLUMBIA,MO. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. RP Dorgan, JF (reprint author), NCI,DIV CANC PREVENT & CONTROL,EXECUT PLAZA N,ROOM 211,6130 EXEXCUT BLVD,MSC 732,BETHESDA,MD 20892, USA. RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X NR 10 TC 54 Z9 56 U1 0 U2 0 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 1997 VL 105 SU 3 BP 583 EP 585 DI 10.2307/3433374 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA XB828 UT WOS:A1997XB82800006 PM 9167999 ER PT J AU Ursin, G London, S Stanczyk, FZ Gentzschein, E PaganiniHill, A Ross, RK Pike, MC AF Ursin, G London, S Stanczyk, FZ Gentzschein, E PaganiniHill, A Ross, RK Pike, MC TI A pilot study of urinary estrogen metabolites (16 alpha-OHE1 and 2-OHE1) in postmenopausal women with and without breast cancer SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Workshop on Hormones, Hormone Metabolism, Environment, and Breast Cancer CY SEP 28-29, 1995 CL NEW ORLEANS, LA DE estrogen metabolism; 16 alpha-hydroxyestrone; 2-hydroxyestrone; breast cancer; urinary estrogen metabolites ID POST-MENOPAUSAL WOMEN; HORMONE-BINDING GLOBULIN; PROTEIN-BOUND ESTRADIOL; OXIDATIVE-METABOLISM; SERUM CONCENTRATIONS; RISK; DISEASE; ESTRIOL; PLASMA; DIET AB The two main pathways for metabolizing estrogen are via 16 alpha-hydroxylation and 2-hydroxylation. The 16 alpha-hydroxy metabolites are biologically active; the 2-hydroxy metabolites are not. It is suggested that women who metabolize a larger proportion of their endogenous estrogen via the 16 alpha-hydroxy pathway may be al significantly elevated risk of breast cancer compared with women who metabolize proportionally more estrogen via the 2-hydroxy pathway. In particular, it is suggested that the ratio of urinary 2-hydroxyestrone (2-OHE1) to 16 alpha-hydroxyestrone (16 alpha-OHE1) is an index of reduced breast cancer risk. This pilot study compared this ratio in postmenopausal women diagnosed with breast cancer to those of healthy controls. Urinary concentrations of estrone (E-1), 17 beta-estradiol (E-2) and estriol (E-3) were also quantified. White women who were subjects in a previous breast cancer case-control study at our institution were eligible for inclusion. All participants provided a sample of their first morning urine. The results from the first 25 cases and 23 controls are presented here. The ratio of 2-OHE1 to 16 alpha-OHE1 was 12% lower in the cases (p = 0.58). However, urinary E-1 was 30% higher (p = 0.10), E-2 was 58% higher (p = 0.07), E-3 was 15% higher (p = 0.48), and the sum of E-1, E-2, and E-3 was 22% higher (p = 0.16) in the cases. These preliminary results do not support the hypothesis that the ratio of the two hydroxylation metabolites (2-OHE1/16 alpha-OHE1) is an important risk factor for breast cancer or that it is a better predictor of breast cancer risk than levels of E-1, E-2 and E-3 measured in urine. C1 NATL INST ENVIRONM HLTH SCI,RES TRIANGLE PK,NC. UNIV SO CALIF,LOS ANGELES CTY WOMENS HOSP,DEPT OBSTET & GYNECOL,LOS ANGELES,CA. RP Ursin, G (reprint author), UNIV SO CALIF,KENNETH NORRIS JR COMPREHENS CANC CTR,DEPT PREVENT MED,1441 EASTLAKE AVE,MS 44,LOS ANGELES,CA 90033, USA. OI London, Stephanie/0000-0003-4911-5290 FU NCI NIH HHS [5 P01 CA 17054] NR 49 TC 41 Z9 43 U1 0 U2 1 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 1997 VL 105 SU 3 BP 601 EP 605 DI 10.2307/3433377 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA XB828 UT WOS:A1997XB82800009 PM 9168002 ER PT J AU Ziegler, RG Rossi, SC Fears, TR Bradlow, HL Adlercreutz, H Sepkovic, D Kiuru, P Wahala, K Vaught, JB Donaldson, JL Falk, RT Fillmore, CM Siiteri, PK Hoover, RN Gail, MH AF Ziegler, RG Rossi, SC Fears, TR Bradlow, HL Adlercreutz, H Sepkovic, D Kiuru, P Wahala, K Vaught, JB Donaldson, JL Falk, RT Fillmore, CM Siiteri, PK Hoover, RN Gail, MH TI Quantifying estrogen metabolism: An evaluation of the reproducibility and validity of enzyme immunoassays for 2-hydroxyestrone and 16 alpha-hydroxyestrone in urine SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Workshop on Hormones, Hormone Metabolism, Environment, and Breast Cancer CY SEP 28-29, 1995 CL NEW ORLEANS, LA DE breast cancer; estrogen; estrogen metabolites; reproducibility; validity ID BREAST-CANCER RISK; POSTMENOPAUSAL WOMEN; PREMENOPAUSAL WOMEN; ESTRADIOL; HORMONES; DIET; INDOLE-3-CARBINOL; QUANTITATION; RELIABILITY; VEGETARIAN AB Rapid and simple enzyme immunoassays (EIAs) were recently developed to measure 2-hydroxyestrone and 16 alpha-hydroxyestrone in unextracted urine. The balance between these competing estrogen metabolism pathways may serve as a biomarker of breast cancer risk. Before testing these assays in epidemiologic studies, we evaluated their reproducibility, and validity relative to gas chromatography-mass spectroscopy (GC-MS). Overnight 12-hr urine collections from five midfollicular premenopausal women, five midluteal premenopausal women, and five postmenopausal women were aliquoted and stored at -70 degrees C. Two aliquots from each woman were assayed with the EIAs in a random, blinded order, monthly over 4 months and 1 year later. Reproducibility over 4 months was good for both metabolites in premenopausal women (coefficient of variation = 8-14%) and satisfactory in postmenopausal women (similar to 19%). Reproducibility over 12 months remained good in premenopausal women, but was poor in postmenopausal women, with mean readings increasing 50 to 100%. Wide variation in estrogen metabolite levels enabled a single EIA measurement to characterize individual differences among premenopausal women in midfollicular (intraclass correlation coefficient = 98-99%) and midluteal phase (85-91%). A narrower range in metabolite levels among postmenopausal women reduced discrimination (78-82%). The correlation between EIA and GC-MS measurement was excellent for both metabolites (r > 0.9), except for 2-hydroxyestrone in postmenopausal women (r = 0.6). Analysis of absolute agreement suggested that both EIAs were less sensitive than GC-MS, and each detected nonspecific background. The tow concentration of estrogen metabolites in urine from postmenopausal women may explain the problems with reproducibility and validity in this menstrual group. Accordingly, more sensitive EIAs have been developed and are now being evaluated. C1 NCI,DIV CANC ETIOL,BETHESDA,MD 20892. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. CORNELL UNIV,MED CTR,STRANG CORNELL CANC RES LAB,NEW YORK,NY 10021. UNIV HELSINKI,DEPT CLIN CHEM,SF-00100 HELSINKI,FINLAND. UNIV HELSINKI,DEPT CHEM,SF-00100 HELSINKI,FINLAND. MICROBIOL ASSOCIATES INC,ROCKVILLE,MD. NR 28 TC 63 Z9 65 U1 1 U2 2 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 1997 VL 105 SU 3 BP 607 EP 614 DI 10.2307/3433378 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA XB828 UT WOS:A1997XB82800010 PM 9168003 ER PT J AU Tsutsui, T Barrett, JC AF Tsutsui, T Barrett, JC TI Neoplastic transformation of cultured mammalian cells by estrogens and estrogenlike chemicals SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Workshop on Hormones, Hormone Metabolism, Environment, and Breast Cancer CY SEP 28-29, 1995 CL NEW ORLEANS, LA DE estrogens; estrogen metabolites; cell transformation; genotoxicity ID SYRIAN-HAMSTER EMBRYO; SISTER CHROMATID EXCHANGE; EXOGENOUS METABOLIC-ACTIVATION; UNSCHEDULED DNA-SYNTHESIS; SEMINAL-VESICLE CELLS; SPRAGUE-DAWLEY RATS; COVALENT BINDING; BREAST-CANCER; ANEUPLOIDY INDUCTION; V79 CELLS AB Estrogens are clearly carcinogenic in humans and rodents but the mechanisms by which these hormones induce cancer are only partially understood. Stimulation of cell proliferation and gene expression by binding to the estrogen receptor is one important mechanism in hormonal carcinogenesis; however, estrogenicity is not sufficient to explain the carcinogenic activity of all estrogens because some estrogens are not carcinogenic. Estrogens are nonmutagenic in many assays but exhibit specific types of genotoxic activity under certain conditions. We have studied extensively the mechanisms by which estrogens induce neoplastic transformation in a model in vitro system and our findings are summarized in this review. 17 beta-Estradiol (E-2) and diethylstilbestrol (DES) and their metabolites induce morphological and neoplastic transformation of Syrian hamster embryo (SHE) cells that express no measurable levels of estrogen receptor. Treatment of the cells with E-2 or DES fails to induce DNA damage, chromosome aberrations and gene mutations in SHE cells but results in numerical chromosome aberrations (aneuploidy) that could arise from microtubule disruption or disfunction of mitotic apparatus. Estrogen-induced genotoxicity is detected in cells following treatment with estrogen metabolites or following exogenous metabolic activation of estrogens. The estrogens induce DNA adduct formation that is detected by P-32-postlabeling. Both aneuploidy induction and DNA damage caused by DNA adduct formation correlate with the estrogen-induced cell transformation and may tie important in hormonal carcinogenesis. We propose that multiple effects of estrogens acting together cause genetic alterations leading to cell transformation. C1 NIEHS,ENVIRONM CARCINOGENESIS PROGRAM,RES TRIANGLE PK,NC 27709. NIPPON DENT UNIV TOKYO,SCH DENT,DEPT PHARMACOL,TOKYO,JAPAN. NR 89 TC 54 Z9 57 U1 0 U2 0 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 1997 VL 105 SU 3 BP 619 EP 624 DI 10.2307/3433380 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA XB828 UT WOS:A1997XB82800012 PM 9168005 ER PT J AU Allen, RH Gottlieb, M Clute, E Pongsiri, MJ Sherman, J Obrams, GI AF Allen, RH Gottlieb, M Clute, E Pongsiri, MJ Sherman, J Obrams, GI TI Breast cancer and pesticides in Hawaii: The need for further study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Workshop on Hormones, Hormone Metabolism, Environment, and Breast Cancer CY SEP 28-29, 1995 CL NEW ORLEANS, LA DE breast cancer; exposure assessment; Hawaii; endocrine disruption; chlordane/heptachlor; DBCP ID CHEMICALS; ENDOCRINE; HEALTH AB Only 30% of all breast cancer can be explained by known risk factors. Increases in breast cancer incidence rates in Hawaii over the past few decades cannot be attributed solely to improvements in screening and detection. Avoidable environmental factors may contribute to a proportion of the unexplained cases. Emerging evidence on endocrine disruption suggests that environmental chemicals may play a role in the development of breast cancer. Agricultural chemicals, including endocrine disrupters, have been used intensively in Hawaii's island ecosystem over the past 40 years leaching into groundwater, and leading to unusually widespread occupational and general population exposures. This paper discusses breast cancer patterns in Hawaii in the context of documented episodes of exposure to two endocrine-disrupting chemicals, chlordane/heptachlor and 1,2-dibromo-3-chloropropane (DBCP), at levels that sometimes exceeded federal standards by several orders of magnitude. in light of this history, detailed geographic-based studies should be undertaken in Hawaii to elucidate the potential role of environmental factors in the development of breast cancer and other diseases. C1 WORLD RESOURCES INST,HLTH ENVIRONM & DEV PROGRAM,WASHINGTON,DC 20006. UNIV HAWAII,SCH PUBL HLTH,HONOLULU,HI 96822. YALE UNIV,SCH FORESTRY & ENVIRONM STUDIES,NEW HAVEN,CT 06511. WESTERN MICHIGAN UNIV,DEPT SOCIOL,KALAMAZOO,MI 49008. RP Allen, RH (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,EXTRAMURAL EPIDEMIOL & GENET PROGRAM,ROOM 531N,BETHESDA,MD 20892, USA. NR 39 TC 26 Z9 28 U1 0 U2 1 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 1997 VL 105 SU 3 BP 679 EP 683 DI 10.2307/3433389 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA XB828 UT WOS:A1997XB82800021 PM 9168014 ER PT J AU OKeefe, BR Beutler, JA Cardellina, JH Gulakowski, RJ Krepps, BL McMahon, JB Sowder, RC Henderson, LE Pannell, LK Pomponi, SA Boyd, MR AF OKeefe, BR Beutler, JA Cardellina, JH Gulakowski, RJ Krepps, BL McMahon, JB Sowder, RC Henderson, LE Pannell, LK Pomponi, SA Boyd, MR TI Isolation and characterization of niphatevirin, a human-immunodeficiency-virus-inhibitory glycoprotein from the marine sponge Niphates erecta SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE anti-(human immunodeficiency virus); glycoprotein; sponge; CD4; Niphates erecta ID COMBINING SITES; DEXTRAN SULFATE; CD4 MOLECULE; HIV-1; GP120; PURIFICATION; PROTEINS; INTERACT; LECTINS; BINDING AB Anti-human immunodeficiency virus (HIV)-bioassay-guided fractionation of aqueous extracts of the Caribbean sponge Niphates erecta led to isolation of a novel anti-HIV protein, named niphatevirin. The protein was purified to homogeneity by ethanol precipitation, ammonium sulfate precipitation, gel-permeation chromatography and concanavalin-A-Sepharose affinity chromatography. Niphatevirin potently inhibited the cytopathic effects of HIV-1 infection in cultured human lymphoblastoid (CEM-SS) cells; the effective concentration of drug that results in 50% protection of the cells through inhibition of cell lethality, cell-cell fusion and syncytium formation was approximately 10 nM. Delay of addition of niphatevirin to infected cultures by two hours markedly decreased (approximate to 50%) cytoprotection; delay of addition by eight hours resulted in no antiviral activity. Niphatevirin bound to CD4 in a manner that prevented the binding of gp120, but did not directly bind gp120. Niphatevirin (6.5 mu M) was inactive in both hemaglutination and hemolysis assays. Niphatevirin had a molecular mass of about 19 kDa by matrix-assisted laser-desorption ionization-time of flight (MALDI-TOF) mass spectrometry, and a native molecular mass of approximately 18 kDa by gel-filtration chromatography. The protein had an acidic isoelectric point of 4.2-4.6, and was shown by periodate acid Schiff's staining to be glycosylated. C1 NCI, LAB DRUG DISCOVERY RES & DEV, DEV THERAPEUT PROGRAM, DIV CANC TREATMENT DIAG & CTR,FCRDC, FREDERICK, MD 21702 USA. NCI, AIDS VACCINE PROGRAM, SAIC FREDERICK, FREDERICK CANC RES & DEV CTR, BETHESDA, MD 20892 USA. NIDDK, ANALYT CHEM LAB, BETHESDA, MD 20892 USA. HARBOR BRANCH OCEANOG INST INC, DIV BIOMED MARINE RES, FT PIERCE, FL 34946 USA. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 NR 31 TC 22 Z9 24 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD APR 1 PY 1997 VL 245 IS 1 BP 47 EP 53 DI 10.1111/j.1432-1033.1997.t01-1-00047.x PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WT204 UT WOS:A1997WT20400006 PM 9128723 ER PT J AU Oshimura, M Barrett, JC AF Oshimura, M Barrett, JC TI Multiple pathways to cellular senescence: Role of telomerase repressors SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE cellular senescence; telomere; telomerase; multiple pathways; microcell-mediated chromosome transfer ID IMMORTAL HUMAN FIBROBLASTS; ONE COMPLEMENTATION GROUP; HAMSTER EMBRYO CELLS; NEOPLASTIC TRANSFORMATION; CHROMOSOME TRANSFER; CARCINOMA; LINE; GENE; PROGRESSION; ASSIGNMENT AB Telomeres progressively shorten with age in somatic cells in culture and in vivo because DNA replication results in the loss of sequences at the 5' ends of double-stranded DNA. Whereas somatic cells do not express the enzyme, telomerase, which adds repeated telomere sequences to chromosome ends, telomerase activity is detected in immortalised and tumour cells in vitro and in primary tumour tissues. This represents an important difference between normal cells and cancer cells, suggesting that telomere shortening causes cellular senescence. Hybrids between immortal cells and normal cells senesce, indicating that immortal cells have lost, mutated or inactivated genes that are required for the programme of senescence in normal cells. Genes involved in the senescence programme have been mapped to over ten different genetic loci using microcell fusion to introduce human chromosomes and restore the senescence programme. Multiple pathways of cellular senescence have also been demonstrated by chromosome transfer, indicating that the functions of the mapped senescence genes are probably different. One possibility is that one or more of these senescence genes may suppress telomerase activity in immortal cells, resulting in telomere shortening and cellular senescence. To test this hypothesis, telomerase activity and the length of terminal restriction fragments (TRFs) have been examined in microcell hybrids. Re-introduction of a normal chromosome 3 into the renal cell carcinoma cell line RCC23, which has the short arm of chromosome 3, restored cellular senescence. The loss of indefinite growth potential was associated with the loss of telomerase activity and shortening of telomeres in the RCC cells containing the introduced chromosome 3. However, microcell hybrids that escaped from senescence and microcell hybrids with an introduced chromosome 7 or 11 maintained telomere lengths and telomerase activity similar to the parental RCC23. Thus, restoration of cellular senescence by chromosome 3 is associated with repression of telomerase function in RCC cells. This evidence suggests that telomerase suppression is one of several pathways involved in immortalisation. (C) 1997 Elsevier Science Ltd. C1 NIEHS,MOL CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. RP Oshimura, M (reprint author), TOTTORI UNIV,FAC MED,SCH LIFE SCI,DEPT MOL & CELL GENET,NISHIMACHI 86,YONAGO,TOTTORI 683,JAPAN. NR 50 TC 62 Z9 66 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD APR PY 1997 VL 33 IS 5 BP 710 EP 715 DI 10.1016/S0959-8049(97)00090-7 PG 6 WC Oncology SC Oncology GA XA843 UT WOS:A1997XA84300002 PM 9282109 ER PT J AU Vergelli, M Pinet, V Vogt, AB Kalbus, M Malnati, M Riccio, P Long, EO Martin, R AF Vergelli, M Pinet, V Vogt, AB Kalbus, M Malnati, M Riccio, P Long, EO Martin, R TI HLA-DR-restricted presentation of myelin basic protein HLA-DR-restricted presentation of purified myelin basic protein is independent of intracellular processing SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE antigen presentation; cytotoxic T lymphocyte; myelin basic protein; CD4(+) T lymphocyte; human ID CLASS-II MOLECULES; ANTIGEN-PRESENTING CELLS; LIPID-BOUND FORM; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; HISTOCOMPATIBILITY COMPLEX-MOLECULES; INVARIANT CHAIN; SYNTHETIC COPOLYMER-1; SELF-PEPTIDES; MICE LACKING; CNS MYELIN AB Antigen presentation to CD4(+) T cells involves intracellular antigen processing and loading of peptides onto newly synthesized major histocompatibility complex (MHC)-class II molecules. Some antigens, such as the lipid-bound, native form of myelin basic protein (LB-MBP) can also be presented by recycling of cell surface MHC class II molecules. The data reported here demonstrate that a preparation of highly purified, delipidated MBP (HP-MBP) follows yet another presentation pathway Similar to LB-MBP, presentation of HP-MBP to HLA-DR1-restricted T cells was independent of HLA-DM, of newly synthesized proteins, and of invariant chain expression. However, in contrast to LB-MBP, presentation of HP-MBP was also independent of internalization of surface HLA-DR-molecules. The different requirements for the presentation of the two molecular forms of MBP were further confirmed by use of the protease inhibitor E64: presentation of LB-MBP but not of HP MBP was inhibited after treatment of target cells with E64. Furthermore, intact HP-MPB bound to isolated HLA-DR molecules in vitro with an association rate that was considerably faster than that of short peptides. These results show that presentation of HP-MBP is independent of intracellular processing and suggest that it may be presented to T cells by direct binding to surface HLA DR molecules. C1 NINCDS,NEUROIMMUNOL BRANCH,NIH,BETHESDA,MD 20892. NIAID,IMMUNOGENET LAB,NIH,ROCKVILLE,MD 20852. GERMAN CANC RES CTR,DEPT SOMAT GENET,D-6900 HEIDELBERG,GERMANY. UNIV TUBINGEN,DEPT NEUROL,D-7400 TUBINGEN,GERMANY. UNIV BASILICATA,DEPT BIOL DBAF,I-85100 POTENZA,ITALY. UNIV BARI,CSMME,DEPT BIOCHEM & MOL BIOL,BARI,ITALY. RI Long, Eric/G-5475-2011; PINET, Valerie/G-6085-2012 OI Long, Eric/0000-0002-7793-3728; NR 40 TC 42 Z9 42 U1 0 U2 1 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD APR PY 1997 VL 27 IS 4 BP 941 EP 951 DI 10.1002/eji.1830270421 PG 11 WC Immunology SC Immunology GA WU326 UT WOS:A1997WU32600021 PM 9130648 ER PT J AU Skaleric, U Kramar, B Petelin, M Pavlica, Z Wahl, SM AF Skaleric, U Kramar, B Petelin, M Pavlica, Z Wahl, SM TI Changes in TGF-beta(1) levels in gingiva, crevicular fluid and serum associated with periodontal inflammation in humans and dogs SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Article DE TGF-beta(1); gingiva; crevicular fluid; serum; periodontal disease ID GROWTH-FACTOR-BETA; SYNOVIAL INFLAMMATION; TGF-BETA; DISEASE; RECEPTORS AB Transforming growth factor-beta (TGF-beta) represents a family of polypeptide growth factors, involved in embryogenesis, inflammation, regulation of immune responses and wound healing. To determine whether TGF-beta contributes to the evolution of periodontal disease, we assayed TGF-beta levels in gingiva and crevicular fluid of patients with gingivitis and periodontitis. In parallel, TGF-beta was quantified in gingival fluid and serum of beagles with experimentally-induced periodontitis. Disease was monitored by several clinical parameters including Plaque Index, Gingival Index, probing depth, and epithelial attachment loss. Gingival tissues were obtained from 9 patients at the time of periodontal surgery, and gingival fluid samples were collected from an additional population of 10 periodontal patients. In 14 beagles, experimental periodontitis was induced and gingival fluids collected 6 months later. Fluid was collected by paper strips and volume measured by Periotron. Additionally, sera was collected before and 9 months after the ligature-induced periodontitis in 7 beagles. The levels of TGF-beta(1) were measured by ELISA. In the patients, a significantly higher concentration of TGF-beta(1) was observed both in the gingival tissues and fluid samples obtained from the sites with deeper periodontal pockets than in the less involved sites. In beagles, TGF-beta(1) levels measured in gingival fluid were elevated in moderate disease, declining in fluid samples obtained from the pockets during more advanced experimental periodontitis. Furthermore, with the progression of experimental periodontitis, a decrease in TGF-beta(1) occurred in the sera of the beagle dogs. These data suggest that TGF-beta(1) may play a role in the pathogenesis and diagnosis of periodontal disease, and that its actions can be further explored in an animal model. C1 UNIV LJUBLJANA,FAC VET,CLIN SURG & SMALL ANIM,LJUBLJANA,SLOVENIA. NIDR,CELLULAR IMMUNOL SECT,IMMUNOL LAB,NIH,BETHESDA,MD 20892. RP Skaleric, U (reprint author), UNIV LJUBLJANA,FAC MED,DEPT ORAL MED & PERIODONTOL,HRVATSKI TRG 6,LJUBLJANA 1000,SLOVENIA. NR 34 TC 49 Z9 50 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0909-8836 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD APR PY 1997 VL 105 IS 2 BP 136 EP 142 DI 10.1111/j.1600-0722.1997.tb00192.x PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA WW951 UT WOS:A1997WW95100005 PM 9151066 ER PT J AU Giambra, LM AF Giambra, LM TI Sustained attention and aging: Overcoming the decrement? SO EXPERIMENTAL AGING RESEARCH LA English DT Article ID AGE AB A literature review found equivocal evidence of a performance decline at senescence on sustained attention (vigilance) tasks. The strongest evidence for such age effects was from Parasuraman and Giambra (PG; 1991). It was hypothesized that reduced perceptual and information-processing abilities of older adults (i.e., non-sustained attentional components of the task) were responsible for the age effects reported by PG and that such outcomes could be eliminated or reduced by minimizing the influence of those components. in Tasks 1 (n = 457) and 2 (n = 427), which used PG's procedure and stimulus conditions, age effects on detection accuracy and on the detection time decrement were not found. False alarms were significantly greater in the old group than in the young group. In Task 3 (n = 417), which minimized non-sustained attention components, some marginal evidence of age effects emerged. Potential explanations of these outcomes, such as an extremely small age effect, sampling bias, power differences, and undetected visual difficulties are considered, and further manipulations and controls are proposed. RP Giambra, LM (reprint author), NIDA,ADDICT RES CTR,LAB PERSONAL & COGNIT,BOX 03,4040 EASTER AVE,BALTIMORE,MD 21224, USA. NR 10 TC 11 Z9 13 U1 0 U2 3 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0361-073X J9 EXP AGING RES JI Exp. Aging Res. PD APR-JUN PY 1997 VL 23 IS 2 BP 145 EP 161 DI 10.1080/03610739708254030 PG 17 WC Geriatrics & Gerontology; Psychology SC Geriatrics & Gerontology; Psychology GA WX908 UT WOS:A1997WX90800003 PM 9151075 ER PT J AU Ryan, JJ Huang, H McReynolds, LJ Shelburne, C HuLi, J Huff, TE Paul, WE AF Ryan, JJ Huang, H McReynolds, LJ Shelburne, C HuLi, J Huff, TE Paul, WE TI Stem cell factor activates STAT-5 DNA binding in IL-3-derived bone marrow mast cells SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE c-kit; SCF; tyrosine kinase receptor; STAT-5; erythropoietin ID COLONY-STIMULATING FACTOR; HEMATOPOIETIC-CELLS; TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; RECEPTOR; ERYTHROPOIETIN; PROTOONCOGENE; ASSOCIATION; KINASE; SITE AB The Kit tyrosine kinase regulates growth and differentiation of many hematopoietic cells through a signal transduction process that remains to be fully elucidated. Kit has been shown to associate with the receptor for erythropoietin (Epo), which is known to activate the signal transducer and activator of transcription, STAT-5. To determine if Kit signal transduction activated latent DNA-binding factors, including STAT-5, we performed electrophoretic mobility shift assays on stem cell factor (SCF)-stimulated mouse bone marrow-derived mast cells (BMMCs). SCF led to the rapid and transient activation of a DNA-binding factor that was identified by supershift analysis as STAT-5. STAT-5 DNA binding was shown to be specific for the oligonucleotide of the correct sequence and was dose-responsive. Epo stimulation of BMMCs led to the activation of a DNA-binding activity that comigrated with the SCF-induced band, but peaked and was maintained at later time points than SCF-induced activation. These data indicate that SCF stimulation of Kit leads to activation of STAT-5 DNA binding with kinetics distinct from Epo-mediated stimulation. C1 VIRGINIA COMMONWEALTH UNIV,DEPT MICROBIOL & IMMUNOL,RICHMOND,VA 23298. RP Ryan, JJ (reprint author), NIAID,IMMUNOL LAB,NIH,10 CTR DR MSC 1892,BLDG 10,ROOM 11N311,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [R01AI25537] NR 26 TC 46 Z9 46 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD APR PY 1997 VL 25 IS 4 BP 357 EP 362 PG 6 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA WV895 UT WOS:A1997WV89500012 PM 9131012 ER PT J AU Gao, WQ Weil, RJ DugichDjordjevic, M Lu, B AF Gao, WQ Weil, RJ DugichDjordjevic, M Lu, B TI The therapeutic potentials of neurotrophic factors for diseases of the nervous system SO EXPERT OPINION ON THERAPEUTIC PATENTS LA English DT Review ID MIDBRAIN DOPAMINERGIC-NEURONS; BASAL FOREBRAIN LESIONS; GROWTH-FACTOR; ALZHEIMERS-DISEASE; CELL-LINE; IN-VIVO; CHOLINERGIC NEURONS; CONTINUOUS INFUSION; PARKINSONS-DISEASE; KINASE-ACTIVITY AB Neurotrophic factors are secreted proteins that regulate the long-term survival and differentiation of neurones in the peripheral and central nervous systems (PNS and CNS). Their profound effects on the structural integrity of the nervous system have led to intense interest in the potential use of the factors as therapeutic agents for neurodegenerative diseases. In the present review, we summarise the current data on the physiological role of these proteins based on in vitro investigations and animal models, and discuss their clinical potential as therapeutic agents in the treatment of neurological disorders. A rationale for neurotrophic factor therapy can be built for a specific neurological disease once a particular neurotrophic factor is identified to regulate vulnerable neurones in the affected areas. Progress has been made in the use of neurotrophic factors as an alternative therapy to conventional drug treatment, particularly for Alzheimer's disease, Parkinson's disease and peripheral neuropathy. Production of chimeric neurotrophins may combine the beneficial aspects of a number of neurotrophic factors. Delivery of exogenous protein factors to the CNS remains one of the major obstacles for trophic factor therapy. Second generation approaches (including transplantation of genetically engineered cells, direct gene transfer into the brain and pharmacological manipulation of the levels of endogenous neurotrophic factors) may prove to be effective in overcoming the technical problems surrounding direct CNS delivery. The discovery of new trophic molecules and development of novel delivery methods represent two important aspects of neurotrophic therapy for neurodegenerative diseases. C1 NICHHD,DEV NEUROBIOL LAB,NIH,BETHESDA,MD 20892. NICHD,DEV NEUROBIOL LAB,NIH,BETHESDA,MD 20892. GENENTECH INC,DEPT NEUROSCI,S SAN FRANCISCO,CA 94080. NR 105 TC 17 Z9 18 U1 0 U2 1 PU ASHLEY PUBL LTD PI LONDON PA 1ST FL, THE LIBRARY, 1 SHEPHERDS HILL HIGHGATE, LONDON, ENGLAND N6 5QJ SN 1354-3776 J9 EXPERT OPIN THER PAT JI Expert Opin. Ther. Patents PD APR PY 1997 VL 7 IS 4 BP 325 EP 338 DI 10.1517/13543776.7.4.325 PG 14 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WR747 UT WOS:A1997WR74700004 ER EF