FN Thomson Reuters Web of Science™ VR 1.0 PT J AU IWASAKI, M DAVIS, DG DARDEN, TA PEDERSEN, LG NEGISHI, M AF IWASAKI, M DAVIS, DG DARDEN, TA PEDERSEN, LG NEGISHI, M TI MULTIPLE STEROID-BINDING ORIENTATIONS - ALTERATION OF REGIOSPECIFICITY OF DEHYDROEPIANDROSTERONE 2-HYDROXYLASE AND 7-HYDROXYLASE ACTIVITIES OF CYTOCHROME-P-450-2A-5 BY MUTATION OF RESIDUE-209 SO BIOCHEMICAL JOURNAL LA English DT Article ID AMINO-ACID; 15-ALPHA-HYDROXYLASE; P-45015-ALPHA; SPECTROSCOPY; PROTEINS; EXCHANGE AB The mutation of Ala-117 to Val conferred dehydroepiandrosterone (DHEA) hydroxylase activity on cytochrome P-450 2a-4, with the production of both 2 alpha- and 7 alpha-hydroxyDHEA at similar rates. P-450 2a-5 which has Val at position 117, acquired high DHEA hydroxylase activity by mutation of Phe-209. Mutant F209L of P-450 2a-5 exhibited strong regiospecificity at the 2-position of the DHEA molecule with the production of 2 alpha-hydroxy DHEA as the major metabolite. On the other hand, mutant F209V of P-450 2a-5 showed the 7-position to be the major hydroxylation site, 7 beta-hydroxyDHEA and 7 alpha-OHDHEA being produced. Therefore the regiospecificity of DHEA hydroxylase activity of P-450 2a-5 acid at position 209, Modelling of the DHEA molecule in the pocket of bacterial P-450cam showed that the steroid can be accommodated in at least two orientations for which the 2- or 7-position is near the sixth axial position of the haem. Moreover, these two orientations, which are of similar energy, can be interconverted by a 180 degrees rotation of the steroid molecule around its long axis. These results support the hypothesis that the steroid molecule in the pocket is in dynamic equilibrium with multiple binding orientations and that the equilibrium is apparently determined by a few critical residues including those at positions 117 and 209. C1 NIEHS,NATL INST HLTH,RES TRIANGLE PK,NC 27709. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 NR 23 TC 17 Z9 17 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 FEB 15 PY 1995 VL 306 BP 29 EP 33 PN 1 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QH166 UT WOS:A1995QH16600005 PM 7864823 ER PT J AU HOWARD, OMZ KIRKEN, RA GARCIA, GG HACKETT, RH FARRAR, WL AF HOWARD, OMZ KIRKEN, RA GARCIA, GG HACKETT, RH FARRAR, WL TI STRUCTURAL DOMAINS OF INTERLEUKIN-2 RECEPTOR-BETA CRITICAL FOR SIGNAL-TRANSDUCTION - KINASE ASSOCIATION AND NUCLEAR COMPLEX-FORMATION SO BIOCHEMICAL JOURNAL LA English DT Article ID PROTEIN-TYROSINE KINASES; COLONY-STIMULATING FACTOR; GROWTH-HORMONE RECEPTOR; HUMAN IL-2 RECEPTOR; HUMAN T-CELLS; GAMMA-CHAIN; CYTOPLASMIC REGIONS; PHOSPHORYLATION; SUBUNIT; ACTIVATION AB The structural domains of interleukin-2 receptor beta (IL-2R beta) were examined, characterizing the protein domains, associated phosphoproteins and nuclear complexes of IL-2-induced signal transduction. A series of IL-2R beta cytoplasmic deletion mutants were constructed and transfected into a murine pre-B-cell line, Ba/F3. The proliferative response of characterized clones was determined. A minimal linear cytoplasmic sequence required for proliferation and a sequence motif (PQPLXP) needed along with Box1-Box2 for IL-2-induced proliferation were identified, Anti-phosphotyrosine Western-blot analysis of a stimulated biologically active clone showed several IL-2-induced tyrosylphosphorylated proteins with molecular masses ranging from 45 to 116 kDa. In vitro kinase studies of biologically active clone-receptor complexes showed a 116 kDa protein (p116) to be the major tyrosine-phosphorylated component. The presence of the p116 kinase in the receptor complex correlates with IL-2-induced proliferation. An IL-2-inducible p116 kinase has recently been characterized as a Jak kinase family member and named Jak3. Nuclear complexes were formed with the GRR oligomer only when the IL-2R beta mutant supported proliferation. This led us to conclude that Box1-Box2 and PQPLXP motifs associate with Jak3 and that this association is an essential element in the IL-2 signal-transduction pathway culminating in the formation of a nuclear complex. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702. US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20892. RP HOWARD, OMZ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702, USA. RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 NR 50 TC 21 Z9 22 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD FEB 15 PY 1995 VL 306 BP 217 EP 224 PN 1 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QH166 UT WOS:A1995QH16600032 PM 7532397 ER PT J AU LESCH, KP GROSS, J FRANZEK, E WOLOZIN, BL RIEDERER, P MURPHY, DL AF LESCH, KP GROSS, J FRANZEK, E WOLOZIN, BL RIEDERER, P MURPHY, DL TI PRIMARY STRUCTURE OF THE SEROTONIN TRANSPORTER IN UNIPOLAR DEPRESSION AND BIPOLAR DISORDER SO BIOLOGICAL PSYCHIATRY LA English DT Article DE SEROTONIN TRANSPORTER; POLYMERASE CHAIN REACTION; DNA SEQUENCE VARIANTS; DEPRESSION; BIPOLAR DISORDER ID IMIPRAMINE BINDING-SITES; TRITIATED IMIPRAMINE; BLOOD-PLATELETS; GENE; MUTATIONS; ILLNESS; BRAIN; 5-HYDROXYTRYPTAMINE; LINKAGE; CLONING AB Genetic factors have been implicated in the etiology of affective disorders but due to the complex inheritance patterns of these disorders, identification of the responsible gene(s) has so far been unsuccessful. Decreased platelet serotonin (5-HT) transport and reduced binding of imipramine or paroxetine to brain and platelet 5-HT uptake sites/transporters in patients with depression and suicide victims define the 5-HT transporter (5-HTT) as a candidate gene. The primary structure of the 5-HTT was analyzed in 17 patients meeting DSM-III-R diagnostic criteria for major depressive or bipolar disorder and in 4 healthy controls using polymerase chain reaction (PCR-) amplification and sequencing of complementary deoxyribose- nucleic acid (cDNA) synthesized from platelet 5-HTT messenger ribose nucleic acid (mRNA). Direct PCR sequencing of the protein coding region failed to reveal changes in the deduced amino acid sequence of the platelet/brain 5-HTT (40,000 base pairs sequence screened), although a conservative single-base substitution representing a silent polymorphism was found. The results provide preliminary evidence that alterations in the primary structure of 5-HTT are not generally involved in the pathogenesis of unipolar depression and manic-depressive illness. C1 NIMH,CTR CLIN,LCS,BETHESDA,MD. RP LESCH, KP (reprint author), UNIV WURZBURG,DEPT PSYCHIAT,FUECHSLEINSTR 15,D-97080 WURZBURG,GERMANY. RI Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X NR 47 TC 95 Z9 97 U1 1 U2 1 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiat. PD FEB 15 PY 1995 VL 37 IS 4 BP 215 EP 223 DI 10.1016/0006-3223(94)00147-U PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA QF436 UT WOS:A1995QF43600002 PM 7711157 ER PT J AU ELMALLAKH, RS WYATT, RJ AF ELMALLAKH, RS WYATT, RJ TI THE NA,K-ATPASE HYPOTHESIS FOR BIPOLAR ILLNESS SO BIOLOGICAL PSYCHIATRY LA English DT Review DE BIPOLAR ILLNESS; CALCIUM; LITHIUM; MANIC-DEPRESSION; NA,K-ATPASE; POTASSIUM; SODIUM ID ADENOSINE-TRIPHOSPHATASE ACTIVITY; MANIC-DEPRESSIVE PSYCHOSIS; HUMAN CEREBROSPINAL-FLUID; MEMBRANE CATION CARRIER; INTRACELLULAR CALCIUM-CONCENTRATION; POSITRON EMISSION TOMOGRAPHY; PRIMARY AFFECTIVE-DISORDER; OUABAIN-LIKE COMPOUND; SODIUM-PUMP ACTIVITY; NA+-K+-ATPASE AB A cellular model for bipolar illness is presented. It is propounded that alterations in the activity of the membrane sodium- and potassium-activated adenosine triphosphatase pump (Na,K-ATPase) may be responsible for alterations in neuronal excitability and activity. Specifically, a reduction in Na,K-ATPase activity can lead to both mania and depression by increasing membrane excitability and decreasing neurotransmitter release, respectively. Supporting evidence is reviewed, and clinical and research implications are discussed. C1 NIMH,NEUROPSYCHIAT RES HOSP,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. NR 134 TC 111 Z9 114 U1 0 U2 6 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiat. PD FEB 15 PY 1995 VL 37 IS 4 BP 235 EP 244 DI 10.1016/0006-3223(94)00201-D PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA QF436 UT WOS:A1995QF43600005 PM 7711160 ER PT J AU SPANGRUDE, GJ BROOKS, DM TUMAS, DB AF SPANGRUDE, GJ BROOKS, DM TUMAS, DB TI LONG-TERM REPOPULATION OF IRRADIATED MICE WITH LIMITING NUMBERS OF PURIFIED HEMATOPOIETIC STEM-CELLS - IN-VIVO EXPANSION OF STEM-CELL PHENOTYPE BUT NOT FUNCTION SO BLOOD LA English DT Article ID BONE-MARROW; PROLIFERATIVE CAPACITY; MOUSE; TRANSPLANTATION; RHODAMINE-123; SPLEEN; LIN; DIFFERENTIATION; PURIFICATION; ORGANIZATION AB Hematopoietic stem cells were isolated from normal adult mouse bone marrow based on surface antigen expression (Thy-1.1(low)Lin(neg)Ly-6A/E(+)) and further selected for low retention of rhodamine 123. This population of cells (Rh-123(low)) could mediate radioprotection and long-term (:greater than 12 months) repopulation after transplantation of as few as 25 cells. Transfer of five genetically marked Rh-123(low) cells in the presence of 10(5) normal bone marrow cells resulted in reconstitution of peripheral blood by greater than 10% donor cells in 64% (30 of 47) of recipient mice. Of 46 animals surviving after 24 weeks, 10 had over 50% donor-derived cells in peripheral blood. Two general patterns of long-term reconstitution were observed: one in which many donor-derived cells were observed 5 to 6 weeks after reconstitution and another in which donor-derived cells were rare initially but expanded with time. This result suggests that two classes of long-term repopulating hematopoietic stem cells exist, differing in their ability to function early in the course of transplantation. Alternatively, distinct anatomic sites of engraftment may dictate these two outcomes from a single type of cell. As an approach to measure the extent of self-renewal by the injected cells, recipients of five or 200 stem cells were killed 8 to 13 months after the transplants, and Thy-1,1(low)Lin(neg)Ly-6A/E(+) progeny of the original injected cells were isolated for a second transplant. While a numerical expansion of cells expressing the cell surface phenotype of stem cells was observed, along with activity in the colony-forming unit-spleen assay, the expanded cells were vastly inferior in radioprotection and long-term reconstitution assays when compared with cells freshly isolated from normal animals. This result demonstrates that in stem cell expansion experiments, cell surface antigen expression is not an appropriate indicator of stem cell function. C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. NR 40 TC 252 Z9 254 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 FEB 15 PY 1995 VL 85 IS 4 BP 1006 EP 1016 PG 11 WC Hematology SC Hematology GA QG993 UT WOS:A1995QG99300018 PM 7849289 ER PT J AU DEMENDEZ, I LETO, TL AF DEMENDEZ, I LETO, TL TI FUNCTIONAL RECONSTITUTION OF THE PHAGOCYTE NADPH OXIDASE BY TRANSFECTION OF ITS MULTIPLE COMPONENTS IN A HETEROLOGOUS SYSTEM SO BLOOD LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; GTP-BINDING PROTEIN; RESPIRATORY BURST OXIDASE; LEUKEMIA CELL-LINE; SUPEROXIDE GENERATION; MEDIATED EXPRESSION; HUMAN-NEUTROPHILS; PLASMA-MEMBRANE; CYTOCHROME-B; KINASE-C AB The phagocyte NADPH oxidase system, as previously defined by cell-free reconstitution, is comprised of five essential components, three of which are produced during late phagocytic differentiation-namely, two cytosolic proteins, p47- and p67-phox-and the large subunit of cytochrome b(558), gp91-phox. To confirm that these are the only phagocyte-specific components necessary for oxidase activity in whole cells, the recombinant NADPH oxidase was reconstituted in a heterologous cell line. An undifferentiated multipotent leukemic cell line, K562, which expresses endogenous Rac and the small subunit of the flavocytochrome b(558) (p22-phox), was cotransfected with episomal expression vectors containing cDNAs for the three other oxidase components. After 4 days of selection, the complete oxidase system was functionally reconstituted in transfected cells stimulated with phorbol myristate acetate or calcium ionophore. These easily transfected cells provide an ideal model system in which several oxidase components can be genetically manipulated and readily expressed. This system can be used to test the effects of mutations associated with any of the genes affected in chronic granulomatous disease and will facilitate studies on structure-function relationships within several oxidase components. This system will also aid in delineation of upstream regulators functioning through various signaling pathways. C1 NIAID,HOST DEFENSES LAB,BETHESDA,MD 20892. NR 43 TC 45 Z9 47 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 FEB 15 PY 1995 VL 85 IS 4 BP 1104 EP 1110 PG 7 WC Hematology SC Hematology GA QG993 UT WOS:A1995QG99300028 PM 7849298 ER PT J AU TARONE, RE AF TARONE, RE TI THE EXCESS OF PATIENTS WITH ADVANCED BREAST-CANCER IN YOUNG-WOMEN SCREENED WITH MAMMOGRAPHY IN THE CANADIAN NATIONAL BREAST SCREENING STUDY SO CANCER LA English DT Article DE BREAST CANCER; MAMMOGRAPHY; PSEUDO-VARIABLE; RANDOMIZED TRIAL ID RETRACTS WARNINGS; DEATH RATES; TRIAL; MORTALITY; AUTHOR AB Background. An unexpected excess of patients with breast cancer with four or more positive lymph nodes was observed in mammographically screened women who were younger than the age of 50 years at enrollment into the Canadian National Breast Screening Study (NBSS), It has been suggested that this excess is consistent with prior screening trials evaluating mammography. Methods. A quantitative evaluation of the distribution of patients with breast cancer with four or more positive lymph nodes in the NESS was undertaken, and the percentages of patients with breast cancer who were at an advanced state at diagnosis in the NESS and in previous randomized screening trials were compared. The validity of mortality analyses after eliminating advanced cases detected by physical examination at the initial screening visit is examined. Results. The excess of patients with cancer with four or more positive lymph nodes in the 40-49-year mammography age group of the NESS was statistically significant, even when expressed as a percentage of all invasive cancers diagnosed. Such an excess is inconsistent with published data on extent of disease at diagnosis from previous studies. Analysis of NESS mortality data after eliminating advanced cases detected by physical examination at the initial visit should result in minimal, if any, bias. Conclusions. Mortality analyses eliminating advanced cases detected by physical examination at the initial screening visit may be less susceptible to bias caused by possible nonrandom allocation of study participants and should be considered in future evaluations of the NESS cohort after longer follow-up periods and in meta-analyses that may include the NESS in assessments of the efficacy of mammography. RP TARONE, RE (reprint author), NCI,BIOSTAT BRANCH,EPN 403,BETHESDA,MD 20892, USA. NR 29 TC 70 Z9 70 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 0008-543X J9 CANCER JI Cancer PD FEB 15 PY 1995 VL 75 IS 4 BP 997 EP 1003 DI 10.1002/1097-0142(19950215)75:4<997::AID-CNCR2820750415>3.0.CO;2-M PG 7 WC Oncology SC Oncology GA QG336 UT WOS:A1995QG33600014 PM 7842421 ER PT J AU MACFARLANE, MP YANG, JC GULERIA, AS WHITE, RL SEIPP, CA EINHORN, JH WHITE, DE ROSENBERG, SA AF MACFARLANE, MP YANG, JC GULERIA, AS WHITE, RL SEIPP, CA EINHORN, JH WHITE, DE ROSENBERG, SA TI THE HEMATOLOGIC TOXICITY OF INTERLEUKIN-2 IN PATIENTS WITH METASTATIC MELANOMA AND RENAL-CELL CARCINOMA SO CANCER LA English DT Article DE INTERLEUKIN-2; ANEMIA; THROMBOCYTOPENIA; COAGULATION DEFECT; LYMPHOCYTOSIS; LYMPHOPENIA; TRANSFUSION; HEMORRHAGE; RENAL CELL CARCINOMA; MELANOMA; IMMUNOTHERAPY ID HIGH-DOSE INTERLEUKIN-2; ACTIVATED KILLER-CELLS; PHASE-II TRIAL; CANCER-PATIENTS; IMMUNOTHERAPY AB Background. High dose interleukin-2 (IL-2) has been found to produce durable antitumor responses in some patients, benefiting most greatly those patients with melanoma and renal cell carcinoma. In this paper, the hematologic toxicity and changes resulting from high dose IL-2 alone administered by intravenous bolus are discussed. Methods. One hundred ninety-nine consecutive patients treated with high dose IL-2 alone from January 1, 1988 to December 31, 1992 were included in this study. All patients had a diagnosis of metastatic melanoma or metastatic renal cell carcinoma and were treated at the National Cancer Institute (Bethesda, MD). Results. Anemia, requiring erythrocyte transfusions, occurred in 14% of all treatment courses, with a median of two units of erythrocytes transfused. Severe leukopenia (<1,000 leukocytes/mm(3)) was rare (1.5% of all patients) and was not associated with any infectious complications. Severe thrombocytopenia (<30,000 platelets/mm(3)) occurred in 2.2% of all treatment cycles, with two patients experiencing a grade 3 hemorrhage, defined as gross blood loss, and one patient experiencing a grade 4 hemorrhage, defined as a debilitating blood loss. Defects in the coagulation pathway were common: abnormal partial thromboplastin time and prothrombin time values occurred in 64% and 25% of the treatment cycles, respectively. In addition, a mean clearance of 93% of lymphocytes from the peripheral blood was observed within 24 hours after initiating IL-2 therapy. This was followed by rebound lymphocytosis to a mean of 198% of baseline on posttreatment Day 4. There were no treatment-related deaths. Conclusions. During IL-2 therapy, adverse sequelae of anemia, thrombocytopenia, coagulopathy, and leukopenia were usually mild, transient and rarely limited therapy. A profound decrease in lymphocytes in the peripheral circulation occurred within 24 hours after initiating therapy, with a rebound occurring after stopping IL-2. No specific hematologic parameter was associated significantly with a patient's increased probability of responding to therapy. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. NR 20 TC 33 Z9 33 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 0008-543X J9 CANCER JI Cancer PD FEB 15 PY 1995 VL 75 IS 4 BP 1030 EP 1037 DI 10.1002/1097-0142(19950215)75:4<1030::AID-CNCR2820750420>3.0.CO;2-5 PG 8 WC Oncology SC Oncology GA QG336 UT WOS:A1995QG33600019 PM 7842405 ER PT J AU COLE, DJ WEIL, DP SHILYANSKY, J CUSTER, M KAWAKAMI, Y ROSENBERG, SA NISHIMURA, MI AF COLE, DJ WEIL, DP SHILYANSKY, J CUSTER, M KAWAKAMI, Y ROSENBERG, SA NISHIMURA, MI TI CHARACTERIZATION OF THE FUNCTIONAL SPECIFICITY OF A CLONED T-CELL RECEPTOR HETERODIMER RECOGNIZING THE MART-1 MELANOMA ANTIGEN SO CANCER RESEARCH LA English DT Note ID TUMOR-INFILTRATING LYMPHOCYTES; CHAIN; IMMUNOTHERAPY; RECOGNITION; CANCER AB T cells can play a central role in the immune response to cancer, with tumor-specific T-lymphocyte reactivity provided by the T-cell receptor (TCR) alpha and beta chain heterodimer. This study is the first report of the definitive identification and characterization of a functional tumor-associated, antigen-specific TCR by reconstitution in an alternate cell line. Jurkat T cells were transfected with the cDNAs encoding the full-length alpha and beta T-cell receptor chains from the HLA-AZ restricted, melanoma-reactive T-cell clone, clone 5. Expression of the transfected TCR was evaluated by immunofluorescence after down-modulation of the endogenous receptor with Jurkat T-cell receptor beta chain-specific mAb. Jurkat clone 5 TCR(+) cells recognized MART-1 peptides presented by T2 cells in a pattern and sensitivity equivalent to native MART-1-reactive T-cells. Recognition of HLA-A2+ melanoma cell lines by the Jurkat clone 5 TCR(+) cells, however, did not occur without the addition of exogenous MART-I peptide. The cloning and expression of functional TCR genes which are capable of specifically recognizing MART-1 antigen provides reagents which could be used for the study of the mechanisms of T-cell/tumor antigen interactions and creates immortalized reagents which can facilitate studies requiring detection of the MART-1 antigen. The tumor reactivity provided by these genes could also have application in novel immunotherapeutic strategies for treating patients with melanoma, including redirection of tumor-infiltrating lymphocyte specificity and bone marrow stem cell therapy. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. RI Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 NR 26 TC 65 Z9 67 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 FEB 15 PY 1995 VL 55 IS 4 BP 748 EP 752 PG 5 WC Oncology SC Oncology GA QG003 UT WOS:A1995QG00300007 PM 7531614 ER PT J AU PONZONI, M BOCCA, P CHIESA, V DECENSI, A PISTOIA, V RAFFAGHELLO, L ROZZO, C MONTALDO, PG AF PONZONI, M BOCCA, P CHIESA, V DECENSI, A PISTOIA, V RAFFAGHELLO, L ROZZO, C MONTALDO, PG TI DIFFERENTIAL-EFFECTS OF N-(4-HYDROXYPHENYL)RETINAMIDE AND RETINOIC ACID ON NEUROBLASTOMA-CELLS - APOPTOSIS VERSUS DIFFERENTIATION SO CANCER RESEARCH LA English DT Article ID HUMAN NEURO-BLASTOMA; DNA FRAGMENTATION; BREAST-CANCER; DEATH; GROWTH; EXPRESSION; INDUCTION; LINES; MORPHOLOGY; INHIBITION AB Retinoids exert various important biological effects in the control of normal growth, differentiation, and fetal development. While retinoic acid (RA) has entered clinical trials as a differentiation-promoting agent, it is only recently that the synthetic retinoid N-(4-hydroxyphenyl)retinamide (EFPR) has been shown to be of potential clinical interest in cancer chemoprevention and treatment. Since thus far no data exist on the effects of HPR on neural crest cell-derived tumors, we have examined its in vitro effects on neuroblastoma (NB) cell Lines and found that at relevant pharmacological concentrations it induces a dose-dependent growth inhibition. The antiproliferative effects of HPR were, in six of six cell lines tested, drastically more potent that those induced by an equimolar dose of RA. Time course growth analysis shelved that HPR at 3 x 10(-6) M induces a very rapid (24-72 h) fall in thymidine uptake (>90%), whereas at 3 x 10(-7) M it exhibits cytostatic effects. In contrast to RA, HPR did not show morphological changes typical of NB cell maturation nor did it induce the expression of any cytoskeletal protein associated with neuronal differentiation. DNA flow cytofluorimetric analysis revealed that HPR did not induce an arrest in a specific phase of the cell cycle while triggering apoptosis. This phenomenon was evidenced both by the visualization of ''DNA ladders'' on gel electrophoresis and by a quantitative assay for evaluating programmed cell death based upon the labeling of DNA breaks with tritiated thymidine. With the latter method, apoptotic cells were detectable as early as 3-6 h after treatment of NB cells with 10(-5) M HPR, while more than 50% of cells were apoptotic by 24-72 h following exposure to 3 x 10(-6) M HPR. In contrast, RA induced a low rate of apoptosis in NB cells only after 3-5 days. Time lapse photomicroscopy showed that NB cells treated with HPR underwent a death process highly reminiscent of apoptosis, with progressive condensation of the cytoplasm around the nucleus and intense cell shrinkage. The cells then rounded up and detached from the plate. Furthermore, propidium iodide staining of the DNA showed that a high proportion of cells treated with HPR displayed a small and brightly staining nucleus; chromatin appeared aggregated into dense masses in the nuclear periphery, a typical feature of apoptotic cells. In conclusion, our study demonstrates that contrary to the differentiation-promoting activity of RA, HPR dramatically suppresses NB cell growth by inducing programmed cell death. Since the peak HPR plasma concentration in patients treated with the drug is superimposable to the dose inducing apoptosis in vitro (i.e., 1-3 x 10(-6) hi), our results may support the hypothesis of the use of HPR in the treatment of advanced neuroblastoma. C1 NATL CANC INST,DEPT MED ONCOL 2,I-16132 GENOA,ITALY. RP PONZONI, M (reprint author), G GASLINI CHILDRENS HOSP,ONCOL RES LAB,LARGO G GASLINI 5,I-16148 GENOA,ITALY. RI Rozzo, Carla/C-4300-2015; Ponzoni, Mirco/J-7713-2016 OI Rozzo, Carla/0000-0001-6581-2227; Ponzoni, Mirco/0000-0002-6164-4286 NR 61 TC 174 Z9 180 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 FEB 15 PY 1995 VL 55 IS 4 BP 853 EP 861 PG 9 WC Oncology SC Oncology GA QG003 UT WOS:A1995QG00300024 PM 7850799 ER PT J AU PLOWMAN, J DYKES, DJ NARAYANAN, VL ABBOTT, BJ SAITO, H HIRATA, T GREVER, MR AF PLOWMAN, J DYKES, DJ NARAYANAN, VL ABBOTT, BJ SAITO, H HIRATA, T GREVER, MR TI EFFICACY OF THE QUINOCARMYCINS KW2152 AND DX-52-1 AGAINST HUMAN-MELANOMA LINES GROWING IN CULTURE AND IN MICE SO CANCER RESEARCH LA English DT Article ID TUMOR-CELL-LINES; ANTICANCER DRUG SCREEN; ANTITUMOR-ACTIVITY; QUINOCARCIN; DC-52 AB Quinocarmycin monocitrate (KW2152) and its analogue, DX-52-1, demonstrated specificity for melanomas in the National Cancer Institute in vitro human tumor cell Line drug screen. In contrast to most cell lines, a 50% I eduction in tumor cell burden (as measured protein) at the end of a 48-h drug incubation was produced in five of eight melanoma lines by KW2152 concentrations (LC(50)s) ranging from 0.49 to 10.93 mu M I and by DX-52-1 concentrations ranging from 0.71 to 7.33 mu M. Using the COMPARE algorithm, the patterns of differential cytotoxicity for both agents at the LC(50) level of effect most closely resembled those for actinomycin D, mithramycin, and Adriamycin. In in vivo studies, both KW2152 (40 mg/kg/day) and DX-52-1 (90 mg/kg/day) caused partial and complete regressions of staged s.c.-implanted LOX IMVI melanoma xenografts following i.p. administration on days 5, 9, and 13 and produced tumor growth delays of 231 and 181%, respectively (P < 0.001). Activity was augmented by more prolonged therapy. Statistically significant growth inhibition of SK-MEL-2, UACC-62, UACC-257, and M14, but not SK-MEL-5 and MALME-3M, melanoma xenografts also was observed following every fourth or seventh day i.p. treatments. Based on these findings, DX-52-1 has been selected by the National Cancer institute for development to clinical trial especially against melanomas. This agent represents one of the first to be selected for preclinical development based on disease-panel specificity discovered in the National Cancer Institute cancer drug screen. C1 NCI, DIV CANC TREATMENT, DEV THERAPEUT PROGRAM, BETHESDA, MD 20892 USA. SO RES INST, BIRMINGHAM, AL 35255 USA. KYOWA HAKKO KOGYO CO LTD, PHARMACEUT RES LABS, SHIZUOKA, JAPAN. FU NCI NIH HHS [N01-CM-97553] NR 27 TC 22 Z9 23 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 15 PY 1995 VL 55 IS 4 BP 862 EP 867 PG 6 WC Oncology SC Oncology GA QG003 UT WOS:A1995QG00300025 PM 7850800 ER PT J AU PANZA, JA DILSIZIAN, V LAURIENZO, JM CURIEL, RV KATSIYIANNIS, PT AF PANZA, JA DILSIZIAN, V LAURIENZO, JM CURIEL, RV KATSIYIANNIS, PT TI RELATION BETWEEN THALLIUM UPTAKE AND CONTRACTILE RESPONSE TO DOBUTAMINE - IMPLICATIONS REGARDING MYOCARDIAL VIABILITY IN PATIENTS WITH CHRONIC CORONARY-ARTERY DISEASE AND LEFT-VENTRICULAR DYSFUNCTION SO CIRCULATION LA English DT Article DE CORONARY DISEASE; MYOCARDIAL CONTRACTION; ECHOCARDIOGRAPHY; SCINTIGRAPHY ID TRANSESOPHAGEAL 2-DIMENSIONAL ECHOCARDIOGRAPHY; LOW-DOSE DOBUTAMINE; STRESS ECHOCARDIOGRAPHY; HIBERNATING MYOCARDIUM; VIABLE MYOCARDIUM; ANATOMIC CORRELATIONS; CLINICAL-APPLICATIONS; TL-201 REINJECTION; IMAGE ORIENTATION; BYPASS SURGERY AB Background Both thallium scintigraphy and dobutamine echocardiography have been used to assess myocardial viability. However, thallium uptake and the inotropic response to dobutamine are expressions of different cellular phenomena. The present study was undertaken to investigate the relation between the two methods in patients with chronic coronary artery disease and left ventricular dysfunction to derive insights into the mechanisms related to myocyte viability. Methods and Results Thirty patients (28 men and 2 women; age, 59+/-10 years) with chronic coronary artery disease and impaired left ventricular systolic function at rest (mean ejection fraction, 32+/-9%) were included in the study. Patients underwent transesophageal echocardiography during incremental doses of dobutamine from 2.5 to a maximum of 40 mu g . kg(-1) . min(-1) and single photon emission computed tomographic thallium scintigraphy using a stress-redistribution-reinjection protocol. The left ventricle was divided into 16 segments for analysis of echocardiographic and thallium images. Segmental myocardial contractile function was graded as normal, hypokinesis, akinesis, or dyskinesis at each incremental dose of dobutamine. Thallium uptake in each myocardial segment was graded on a 5-point scale from 0 (absent) to 2 (normal) for each of the stress, redistribution, and reinjection images. A segment was considered viable if the assigned thallium score was 1 or higher (normal uptake or only mild to moderate defect) in any of the stress, redistribution, or reinjection images. Among 472 myocardial segments available for analysis, 311 had resting wall motion abnormalities, of which 56% (173/311) showed contractile improvement with dobutamine (usually first observed at less than or equal to 10 mu g . kg(-1) . min(-1)) and 84% (262/311) were considered viable by thallium scintigraphy (P<.0001). Of the 262 segments considered viable by thallium, 167 (64%) had a contractile improvement with dobutamine; in contrast, only 6 of the 49 segments (12%) considered nonviable by thallium had a positive dobutamine response (P<.0001). Furthermore, a positive inotropic response to dobutamine was significantly related to the magnitude of thallium uptake: the proportion of segments with a positive dobutamine response rose with increasing magnitude of thallium uptake (P<.001). The disagreement between the two tests was related primarily to segments considered viable by thallium that did not show contractile improvement with dobutamine. Conclusions These findings demonstrate the existence of a relation between thallium uptake and the inotropic response to dobutamine in patients with chronic coronary artery disease and left ventricular dysfunction. However, the proportion of segments showing a positive response to dobutamine is significantly lower than those with thallium uptake, suggesting that the cellular mechanisms responsible for a positive inotropic response to adrenergic stimulation require a higher degree of myocyte functional integrity than those responsible for thallium uptake. RP PANZA, JA (reprint author), NHLBI,CARDIOL BRANCH,ECHOCARDIOG & NUCL CARDIOL LABS,BLDG 10,ROOM 7B-15,BETHESDA,MD 20892, USA. NR 51 TC 158 Z9 163 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 15 PY 1995 VL 91 IS 4 BP 990 EP 998 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA QJ078 UT WOS:A1995QJ07800009 PM 7850986 ER PT J AU PAULY, RR BILATO, C SOLLOTT, SJ MONTICONE, R KELLY, PT LAKATTA, EG CROW, MT AF PAULY, RR BILATO, C SOLLOTT, SJ MONTICONE, R KELLY, PT LAKATTA, EG CROW, MT TI ROLE OF CALCIUM CALMODULIN-DEPENDENT PROTEIN-KINASE-II IN THE REGULATION OF VASCULAR SMOOTH-MUSCLE CELL-MIGRATION SO CIRCULATION LA English DT Article DE CALCIUM; PROTEIN KINASES; MUSCLES, SMOOTH; PLATELET-DERIVED FACTORS; CELLS ID GROWTH-FACTOR; EXPRESSION; GENE; ATHEROSCLEROSIS; PHOSPHORYLATION; INHIBITION; CALPONIN; BRAIN; RHO; RAS AB Background The migration of vascular smooth muscle cells (VSMCs) is a key event in the pathogenesis of many vascular diseases. We have previously shown that VSMC migration in response to platelet-derived growth factor (PDGF) is suppressed when cultured cells are growth-arrested and induced to differentiate. The present study was undertaken to elucidate the mechanism of this suppression. Methods and Results While both proliferating and growth-arrested VSMCs upregulated expression of the immediate early response genes, c-fos and JE (monocyte chemoattractant protein 1), growth-arrested VSMCs exhibited much smaller changes in intracellular calcium in response to PDGF and failed to activate the calcium/calmodulin-dependent protein kinase II (CaM kinase II). Blocking calcium-calmodulin interactions (50 mu mol/L W7) or the activation of CaM kinase II (10 mu mol/L KN62) in proliferating cells blocked their migration by more than 90%, whereas inhibition of protein kinase C activation had no significant effect on migration. Pretreatment of growth-arrested VSMCs with the calcium ionophore ionomycin resulted in an approximately 2.5-fold activation of CaM kinase II and increased migration of growth-arrested cells to 84+/-6% that of proliferating cells. These effects of ionomycin were blocked by inhibitors of CaM kinase II. Constitutively activated (ie, calcium/calmodulin-independent) CaM kinase II introduced by gene transfection into growth-arrested cells significantly increased migration toward PDGF from <20% to >70% that of proliferating cells. Conclusions These results demonstrate that activation of CaM kinase II is required for VSMC migration, that its activation in response to PDGF is suppressed in growth-arrested VSMCs, and that this suppression of CaM kinase II activation is responsible, in large part, for the failure of growth-arrested VSMCs to migrate toward PDGF. C1 NIA,VASC BIOL GRP,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. UNIV TEXAS,SCH MED,DEPT NEUROBIOL & ANAT,HOUSTON,TX 77225. NR 42 TC 90 Z9 93 U1 0 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 15 PY 1995 VL 91 IS 4 BP 1107 EP 1115 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA QJ078 UT WOS:A1995QJ07800024 PM 7850948 ER PT J AU MORGENBESSER, SD SCHREIBERAGUS, N BIDDER, M MAHON, KA OVERBEEK, PA HORNER, J DEPINHO, RA AF MORGENBESSER, SD SCHREIBERAGUS, N BIDDER, M MAHON, KA OVERBEEK, PA HORNER, J DEPINHO, RA TI CONTRASTING ROLES FOR C-MYC AND L-MYC IN THE REGULATION OF CELLULAR GROWTH AND DIFFERENTIATION IN-VIVO SO EMBO JOURNAL LA English DT Review DE DIFFERENTIATION; LENS; MYC; PROLIFERATION; TRANSGENIC MICE ID LENS-SPECIFIC EXPRESSION; N-MYC; TRANSGENIC MICE; DNA-BINDING; CHLORAMPHENICOL ACETYLTRANSFERASE; DEREGULATED EXPRESSION; EMBRYONIC LETHALITY; TARGETED DISRUPTION; ONCOGENE EXPRESSION; BURKITT-LYMPHOMA AB Although myc family genes are differentially expressed during development, their expression frequently overlaps, suggesting that they may serve both distinct and common biological functions. In addition, alterations in their expression occur at major developmental transitions in many cell lineages, For example, during mouse lens maturation, the growth arrest and differentiation of epithelial cells into lens fiber cells is associated with a decrease in L- and c-myc expression and a reciprocal rise in N-myc levels. To determine whether the down-regulation of L- and c-myc are required for mitotic arrest and/or completion of differentiation and whether these genes have distinct or similar activities in the same cell type, we have studied the consequences of forced L- and c-myc expression in the lens fiber cell compartment using the alpha A-crystallin promoter in transgenic mice (alpha A/L-myc and alpha A/c-myc mice). With respect to morphological and molecular differentiation, alpha A/L-myc lenses were characterized by a severely disorganized lens fiber cell compartment and a significant decrease in the expression of a late-stage differentiation marker (MIP26); in contrast, differentiation appeared to be unaffected in alpha A/c-myc mice. Furthermore, an analysis of proliferation indicated that while alpha A/L-myc fiber cells withdrew properly from the cell cycle, inappropriate cell cycle progression occurred in the lens fiber cell compartment of alpha A/c-myc mice. These observations indicate that continued late-stage expression of L-myc affected differentiation processes directly, rather than indirectly through deregulated growth control, whereas constitutive c-myc expression inhibited proliferative arrest, but did not appear to disturb differentiation. As a direct corollary, our data indicate that L-Myc and c-Myc are involved in distinct physiological processes in the same cell type. C1 ALBERT EINSTEIN COLL MED,DEPT IMMUNOL MICROBIOL,BRONX,NY 10461. NICHHD,MAMMALIAN GENES & DEV LAB,BETHESDA,MD 20892. BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. FU NCI NIH HHS [CA09173-14, 2P30CA13330-20]; NIGMS NIH HHS [T32 GM07128] NR 106 TC 52 Z9 52 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD FEB 15 PY 1995 VL 14 IS 4 BP 743 EP 756 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QK070 UT WOS:A1995QK07000013 PM 7882978 ER PT J AU CHEN, XY CHAMORRO, M LEE, SI SHEN, LX HINES, JV TINOCO, I VARMUS, HE AF CHEN, XY CHAMORRO, M LEE, SI SHEN, LX HINES, JV TINOCO, I VARMUS, HE TI STRUCTURAL-STUDIES AND FUNCTIONAL-STUDIES OF RETROVIRAL RNA PSEUDOKNOTS INVOLVED IN RIBOSOMAL FRAMESHIFTING - NUCLEOTIDES AT THE JUNCTION OF THE 2 STEMS ARE IMPORTANT FOR EFFICIENT RIBOSOMAL FRAMESHIFTING SO EMBO JOURNAL LA English DT Article DE FRAMESHIFTING; NICKEL COMPLEX; PSEUDOKNOT; RETROVIRUS ID POLYMERASE-III HOLOENZYME; ESCHERICHIA-COLI; MESSENGER-RNA; GENE-EXPRESSION; FUSION PROTEIN; GAMMA-SUBUNIT; VIRUS; TRANSLATION; SITE; MECHANISM AB Ribosomal frameshifting, a translational mechanism used during retroviral replication, involves a directed change in reading frame at a specific site at a defined frequency, Such programmed frameshifting at the mouse mammary tumor virus (MMTV) gag-pro shift site requires two mRNA signals: a heptanucleotide shifty sequence and a pseudoknot structure positioned downstream, Using in vitro translation assays and enzymatic and chemical probes for RNA structure, we have defined features of the pseudoknot that promote efficient frameshifting. Heterologous RNA structures, e.g, a hairpin, a tRNA or a synthetic pseudoknot, substituted downstream of the shifty site fail to promote frameshifting, suggesting that specific features of the MMTV pseudoknot are important for function. Site-directed mutations of the MMTV pseudoknot indicate that the pseudoknot junction, including an unpaired adenine nucleotide between the two stems, provides a specific structural determinant for efficient frameshifting, Pseudoknots derived from other retroviruses (i.e. the feline immunodeficiency virus and the simian retrovirus type 1) also promote frameshifting at the MMTV gag-pro shift site, dependent on the same structure at the junction of the two stems. C1 UNIV CALIF BERKELEY,CHEM BIODYNAM LAB,BERKELEY,CA 94720. NCI,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DEPT MICROBIOL & IMMUNOL & BIOCHEM & BIOPHYS,SAN FRANCISCO,CA 94143. BROWN UNIV,MIRIAM HOSP,PROVIDENCE,RI 02906. KENYON COLL,DEPT CHEM,GAMBIER,OH 43022. RP CHEN, XY (reprint author), UNIV CALIF BERKELEY,DEPT CHEM,BERKELEY,CA 94720, USA. FU NCI NIH HHS [CA12705]; NIGMS NIH HHS [GM10840] NR 48 TC 105 Z9 107 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD FEB 15 PY 1995 VL 14 IS 4 BP 842 EP 852 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QK070 UT WOS:A1995QK07000022 PM 7882986 ER PT J AU SUGIYAMA, S UTANI, A YAMADA, S KOZAK, CA YAMADA, Y AF SUGIYAMA, S UTANI, A YAMADA, S KOZAK, CA YAMADA, Y TI CLONING AND EXPRESSION OF THE MOUSE LAMININ GAMMA-2 (B2T) CHAIN, A SUBUNIT OF EPITHELIAL-CELL LAMININ SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE MOUSE LAMININ GAMMA-2 CHAIN; CLONING; SEQUENCE; EXPRESSION; MAPPING ID BASEMENT-MEMBRANE PROTEINS; KALININ; GENE; CHROMOSOME-1; EPILIGRIN; LIGAND; ALPHA-3-BETA-1; ASSIGNMENT; COMPONENT; NICEIN AB We have isolated and sequenced the full-length cDNA for the mouse laminin gamma 2 chain and mapped it to mouse Chromosome 1 proximal to laminin gamma 1. The mRNA for the mouse gamma 2 spans 5.2 kb and codes for a 1192-residue amino acid polypeptide. The gamma 2 chain (formerly termed laminin B2t), a homologue of gamma 1 (formerly B2), lacks an N-terminal domain and has a shorter domain III in comparison to the laminin gamma 1 chain. The expression of the laminin gamma 2 and gamma 1 chains in both newborn and fetal mice was examined by both Northern analysis and in sitar hybridization. mRNA for the laminin gamma 2 chain was expressed specifically by epithelial cells in many tissues with a particularly high level of expression in the tongue, hair follicles, lung and kidney. In contrast, a high level of expression of the laminin gamma 1 chain mRNA was seen in both epithelial and endothelial cells in these tissues. In addition, gamma 1 mRNA was expressed in other tissues such as the nasal septum, blood vessels, and the muscle of the tongue. Immunohistochemistry with an anti-gamma 2 IgG detected strong expression of the laminin gamma 2 chain in the basement membrane of the collecting tubules of the kidney and of the pancreas. Immunoprecipitation studies with antibodies to the gamma 2 chain detected three species at 165, 155 and 140 kDa in HT-1080 cell-conditioned media. This protein complex is characteristic of the kalinin (nicein/epiligrin) complex, and provides further evidence that these proteins are identical and that the gamma 2 chain is the subunit of the epithelial-cell-specific laminin. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD. NR 31 TC 61 Z9 62 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD FEB 15 PY 1995 VL 228 IS 1 BP 120 EP 128 DI 10.1111/j.1432-1033.1995.0120o.x PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QH758 UT WOS:A1995QH75800019 PM 7882992 ER PT J AU BEDELL, MA BRANNAN, CI EVANS, EP COPELAND, NG JENKINS, NA DONOVAN, PJ AF BEDELL, MA BRANNAN, CI EVANS, EP COPELAND, NG JENKINS, NA DONOVAN, PJ TI DNA REARRANGEMENTS LOCATED OVER 100 KB 5' OF THE STEEL (S1) CODING REGION IN STEEL-PANDA AND STEEL-CONTRASTED MICE DEREGULATE S1 EXPRESSION AND CAUSE FEMALE STERILITY BY DISRUPTING OVARIAN FOLLICLE DEVELOPMENT SO GENES & DEVELOPMENT LA English DT Article DE STEEL; GAMETOGENESIS; FEMALE STERILITY; OVARIAN FOLLICLE; POSITION EFFECT MUTATION ID C-KIT LIGAND; CELL GROWTH-FACTOR; TYROSINE KINASE RECEPTOR; PRIMORDIAL GERM-CELLS; W-LOCUS; SI-LOCUS; PROTO-ONCOGENE; MUTANT MICE; MOUSE; RAT AB The Steel (Sl) locus is essential for the development of germ cells, hematopoietic cells, and melanocytes and encodes a growth factor (Mgf) that is the ligand for c-kit, a receptor tyrosine kinase encoded by the W locus. We have identified the molecular and germ cell defects in two mutant SI alleles, Steel-panda (Sl(pan)) and Steel-contrasted (Sl(con)), that cause sterility only in females. Unexpectedly, both mutant alleles are shown to contain DNA rearrangements, located >100 kb 5' of Mgf-coding sequences, that lead to tissue-specific effects on Mgf mRNA expression. In Sl(pan) embryos, decreased Mgf mRNA expression in the gonads causes a reduced number of primordial germ cells in both sexes. However, Mgf expression and spermatogenesis in the postnatal mutant testes is normal, and spermatogonial proliferation compensates for deficiencies in germ cell numbers. In Sl(pan) and Sl(con) homozygous females, decreased Mgf mRNA expression causes sterility by affecting the initiation and maintenance of ovarian follicle development. Thus, regulated expression of Mgf is required for multiple stages of embryonic and postnatal germ cell development. Surprisingly, other areas of the Sl(con) female reproductive tract displayed ectopic expression of Mgf mRNA. We propose that the Sl(pan) and Sl(con) rearrangements alter Mgf mRNA abundance through position effects on expression that act at a distance from the Sl gene. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC GENET DEV SECT,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,ONCOGENESIS SECT,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CELL BIOL DEV & DIFFERENTIAT GRP,FREDERICK,MD 21702. MRC,RADIOBIOL UNIT,DIV GENET,DIDCOT OX11 ORD,OXON,ENGLAND. RI Norman, Robert/A-1155-2007 OI Norman, Robert/0000-0002-3118-3896 FU NCI NIH HHS [N01-CO-46000] NR 59 TC 118 Z9 120 U1 1 U2 3 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD FEB 15 PY 1995 VL 9 IS 4 BP 455 EP 470 DI 10.1101/gad.9.4.455 PG 16 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA QL583 UT WOS:A1995QL58300006 PM 7533739 ER PT J AU BREEN, N AF BREEN, N TI DO SPECIALISTS SCREEN FOR BREAST-CANCER - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP BREEN, N (reprint author), NCI,BETHESDA,MD, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 15 PY 1995 VL 273 IS 7 BP 519 EP 519 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA QF686 UT WOS:A1995QF68600003 ER PT J AU PAHOR, M GURALNIK, JM SALIVE, M AF PAHOR, M GURALNIK, JM SALIVE, M TI PHYSICAL-ACTIVITY AND RISK OF GASTROINTESTINAL HEMORRHAGE IN THE ELDERLY - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP PAHOR, M (reprint author), NIH,BETHESDA,MD, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 15 PY 1995 VL 273 IS 7 BP 522 EP 522 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA QF686 UT WOS:A1995QF68600009 ER PT J AU HARGROVEROBERSON, D JACKSONTHOMPSON, J BOESELAGER, G CAPWELL, E HANN, N LANE, M DIAMOND, R HOLM, K AF HARGROVEROBERSON, D JACKSONTHOMPSON, J BOESELAGER, G CAPWELL, E HANN, N LANE, M DIAMOND, R HOLM, K TI ATTITUDES TOWARD SMOKING POLICIES IN 8 STATES - UNITED-STATES, 1993 (REPRINTED FROM MMWR, VOL 43, PG 786-789, 1994) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 CTR DIS CONTROL,NATL CTR CHRON DIS PREVENT & HLTH PROMOT,OFF SURVEILLANCE & ANAL,ATLANTA,GA 30333. CTR DIS CONTROL,NATL CTR CHRON DIS PREVENT & HLTH PROMOT,OFF SMOKING & HLTH,ATLANTA,GA 30333. RP HARGROVEROBERSON, D (reprint author), NCI,SURVEILLANCE PROGRAM,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 15 PY 1995 VL 273 IS 7 BP 531 EP 532 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QF686 UT WOS:A1995QF68600019 ER PT J AU SHATTUCKEIDENS, D MCCLURE, M SIMARD, J LABRIE, F NAROD, S COUCH, F HOSKINS, K WEBER, B CASTILLA, L ERDOS, M BRODY, L FRIEDMAN, L OSTERMEYER, E SZABO, C KING, MC JHANWAR, S OFFIT, K NORTON, L GILEWSKI, T LUBIN, M OSBORNE, M BLACK, D BOYD, M STEEL, M INGLES, S HAILE, R LINDBLOM, A OLSSON, H BORG, A BISHOP, DT SOLOMON, E RADICE, P SPATTI, G GAYTHER, S PONDER, B WARREN, W STRATTON, M LIU, QY FUJIMURA, F LEWIS, C SKOLNICK, MH GOLDGAR, DE AF SHATTUCKEIDENS, D MCCLURE, M SIMARD, J LABRIE, F NAROD, S COUCH, F HOSKINS, K WEBER, B CASTILLA, L ERDOS, M BRODY, L FRIEDMAN, L OSTERMEYER, E SZABO, C KING, MC JHANWAR, S OFFIT, K NORTON, L GILEWSKI, T LUBIN, M OSBORNE, M BLACK, D BOYD, M STEEL, M INGLES, S HAILE, R LINDBLOM, A OLSSON, H BORG, A BISHOP, DT SOLOMON, E RADICE, P SPATTI, G GAYTHER, S PONDER, B WARREN, W STRATTON, M LIU, QY FUJIMURA, F LEWIS, C SKOLNICK, MH GOLDGAR, DE TI A COLLABORATIVE SURVEY OF 80 MUTATIONS IN THE BRCA1 BREAST-CANCER AND OVARIAN-CANCER SUSCEPTIBILITY GENE - IMPLICATIONS FOR PRESYMPTOMATIC TESTING AND SCREENING SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID FAMILIAL BREAST; RAPID DETECTION; IDENTIFICATION; POLYMORPHISMS; LINKAGE; ONSET AB Objectives.-To report the initial experience of an international group of investigators in identifying mutations in the BRCA1 breast and ovarian cancer susceptibility gene, to assess the spectrum of such mutations in samples from patients with different family histories of cancer, and to determine the frequency of recurrent mutations. Design.-Nine laboratories in North America and the United Kingdom tested for BRCA1 mutations in DNA samples obtained from a total of 372 unrelated patients with breast or ovarian cancer largely chosen from high-risk families. Three of these laboratories also analyzed a total of 714 additional samples from breast or ovarian cancer cases, including 557 unselected for family history, for two specific mutations that had been found to recur in familial samples. Participants.-A total of 1086 women with either breast or ovarian cancer. Main Outcome Measure.-The detection of sequence Variation in patients' DNA samples that is not found in sets of control samples. Results.-BRCA1 mutations have now been identified in a total of 80 patient samples. Thirty-eight distinct mutations were found among 63 mutations identified through a complete screen of the BRCA1 gene. Three specific mutations appeared relatively common, occurring eight, seven, and five times, respectively. When specific tests for the two most common mutations were performed in larger sets of samples, they were found in 17 additional patients, Mutations predicted to result in a truncated protein accounted for 86% of the mutations detected by complete screening. Conclusions.-The high frequency of protein-terminating mutations and the observation of many recurrent mutations found in a diverse set of samples could lead to a relatively simple diagnostic test for BRCA1 mutations. More data must be accumulated to address specifically the sensitivity and specificity of such a diagnostic testing procedure and to better estimate the age-specific risk for breast and ovarian cancer associated with such mutations. C1 UNIV UTAH,SCH MED,DEPT MED INFORMAT,SALT LAKE CITY,UT 84108. MYRIAD GENET,SALT LAKE CITY,UT. CHU LAVAL,RES CTR,DEPT MOLEC ENDOCRINOL,QUEBEC CITY,PQ,CANADA. UNIV LAVAL,QUEBEC CITY,PQ,CANADA. MCGILL UNIV,DEPT MED GENET,MONTREAL,PQ,CANADA. UNIV PENN,DEPT HEMATOL ONCOL,PHILADELPHIA,PA. NATL CTR HUMAN GENOME RES,BETHESDA,MD. UNIV CALIF BERKELEY,DEPT MOLEC BIOL,BERKELEY,CA. UNIV CALIF BERKELEY,DEPT CELL BIOL,BERKELEY,CA. UNIV CALIF BERKELEY,SCH PUBL HLTH,BERKELEY,CA. MEM SLOAN KETTERING CANC CTR,DEPT HUMAN GENET,NEW YORK,NY. MEM SLOAN KETTERING CANC CTR,DEPT ONCOL,NEW YORK,NY. STRANG CANC PREVENT CTR,NEW YORK,NY. BEATSON INST CANC RES,GLASGOW,LANARK,SCOTLAND. UNIV ST ANDREWS,ST ANDREWS,FIFE,SCOTLAND. UNIV SO CALIF,DEPT EPIDEMIOL,LOS ANGELES,CA. KAROLINSKA INST,DEPT CLIN GENET,STOCKHOLM,SWEDEN. LUND UNIV,INST ONCOL,LUND,SWEDEN. IMPERIAL CANC RES FUND,SOMAT CELL GENET LABS,LONDON,ENGLAND. IST NAZL TUMORI,DIV EXPTL ONCOL,MILAN,ITALY. IST NAZL TUMORI,DIV SURG GYNECOL ONCOL,MILAN,ITALY. UNIV CAMBRIDGE,DEPT PATHOL,CRC,HUMAN CANC GENET RES GRP,CAMBRIDGE,ENGLAND. INST CANC RES,MOLEC CARCINOGENESIS SECT,SUTTON,SURREY,ENGLAND. UNIV UTAH,SCH MED,DEPT MED INFORMAT,GENET EPIDEMIOL GRP,SALT LAKE CITY,UT. RI Lewis, Cathryn/A-5225-2010; Radice, Paolo/O-3119-2013 OI Lewis, Cathryn/0000-0002-8249-8476; FU NCI NIH HHS [CA-27632, CA-55914] NR 23 TC 381 Z9 387 U1 0 U2 14 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 FEB 15 PY 1995 VL 273 IS 7 BP 535 EP 541 DI 10.1001/jama.273.7.535 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA QF686 UT WOS:A1995QF68600022 PM 7837387 ER PT J AU POTOSKY, AL MILLER, BA ALBERTSEN, PC KRAMER, BS AF POTOSKY, AL MILLER, BA ALBERTSEN, PC KRAMER, BS TI THE ROLE OF INCREASING DETECTION IN THE RISING INCIDENCE OF PROSTATE-CANCER SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID GEOGRAPHIC-VARIATION; TRENDS AB Objective.-To assess the reasons for the dramatic surge in prostate cancer incidence from 1986 to 1991. Design.-Population-based study of incidence rates and procedures used to detect and diagnose prostate cancer derived from Medicare claims data and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program from 1986 to 1991. Setting.-Four SEER areas (Connecticut; Atlanta, Ga; Detroit, Mich; and Seattle-Puget Sound, Wash) covering approximately 6% of the US population. Participants.-A 5% random sample of male fee-for-service Medicare beneficiaries aged 65 years and older without cancer, and all men with prostate cancer diagnosed at 65 years of age and older residing in the four areas. Main Outcome Measures.-The age-adjusted rates of prostate cancer incidence, prostate needle biopsy, transurethral resection of the prostate, serum prostate-specific antigen (PSA) testing, and transrectal ultrasound. Results.-The age-adjusted incidence rate of prostate cancer among men aged 65 years and older in the four SEER areas rose 82% from 1986 to 1991, with the largest annual increases occurring in 1990 (20%) and 1991 (19%). Prostate needle biopsy rates increased while the use of transurethral resection of the prostate declined from 1986 to 1991. The rising needle biopsy rate has been driven by an exponential increase in PSA testing in the general population from 1988 to 1991 and, to a much lesser extent, the increasing use of transrectal ultrasound since 1986. The use of PSA or transrectal ultrasound has increased across age and race groups and in different geographic areas. However, there remain wide geographic variations in the use of PSA screening. Conclusions.-The recent dramatic epidemic of prostate cancer is likely the result of the increasing detection of tumors resulting from increased PSA screening. The magnitude and rapidity of the incidence rise suggest that changes in the intensity of medical surveillance is the most plausible explanation for this trend. Implications.-The rapid diffusion of screening interventions that have the ability to detect latent asymptomatic disease leads to important concerns regarding costs and patient quality of life for men aged 65 years and older, Geographic variability in the adoption of PSA testing underscores uncertainty and disagreement about its value for reducing prostate cancer mortality. More research is required to determine the effectiveness of screening for prostate cancer. C1 NCI,CANC STAT BRANCH,SURVEILLANCE PROGRAM,BETHESDA,MD. NCI,DIV CANC PREVENT & CONTROL,EARLY DETECT & COMMUNITY ONCOL PROGRAM,BETHESDA,MD. UNIV CONNECTICUT,CTR HLTH,DIV UROL,FARMINGTON,CT. RP POTOSKY, AL (reprint author), NCI,APPL RES BRANCH,6130 EXECUT BLVD,EPN ROOM 313,BETHESDA,MD 20892, USA. NR 33 TC 441 Z9 451 U1 0 U2 7 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 FEB 15 PY 1995 VL 273 IS 7 BP 548 EP 552 DI 10.1001/jama.273.7.548 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA QF686 UT WOS:A1995QF68600024 PM 7530782 ER PT J AU LINEHAN, WM LERMAN, MI ZBAR, B AF LINEHAN, WM LERMAN, MI ZBAR, B TI IDENTIFICATION OF THE VONHIPPEL-LINDAU (VHL) GENE - ITS ROLE IN RENAL-CANCER SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID TUMOR-SUPPRESSOR GENE; CELL CARCINOMA; CYSTIC-DISEASE; RISK-FACTORS; ALLELIC LOSS; SHORT ARM; CHROMOSOME-3; RETINOBLASTOMA; TRANSLOCATION; PAPILLARY C1 NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD. RP LINEHAN, WM (reprint author), NCI,DIV CANC THERAPY,UROL ONCOL SECT,SURG BRANCH,CLIN ONCOL PROGRAM,BLDG 10,ROOM 2B47,BETHESDA,MD 20892, USA. NR 76 TC 182 Z9 183 U1 0 U2 6 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 FEB 15 PY 1995 VL 273 IS 7 BP 564 EP 570 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA QF686 UT WOS:A1995QF68600027 PM 7837390 ER PT J AU TAKESHITA, T TAKAHASHI, H KOZLOWSKI, S AHLERS, JD PENDLETON, CD MOORE, RL NAKAGAWA, Y YOKOMURO, K FOX, BS MARGULIES, DH BERZOFSKY, JA AF TAKESHITA, T TAKAHASHI, H KOZLOWSKI, S AHLERS, JD PENDLETON, CD MOORE, RL NAKAGAWA, Y YOKOMURO, K FOX, BS MARGULIES, DH BERZOFSKY, JA TI MOLECULAR ANALYSIS OF THE SAME HIV PEPTIDE FUNCTIONALLY BINDING TO BOTH A CLASS-I AND A CLASS-II MHC MOLECULE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RESTRICTED T-CELLS; HISTOCOMPATIBILITY COMPLEX-MOLECULES; ENVELOPE PROTEIN; VIRAL PEPTIDES; LYMPHOCYTES-T; HTLV-III; RECOGNITION; ANTIBODIES; ANTIGENS AB Although several peptides have been found to bind to both class I and class II molecules, the basis for this binding of the same peptide to two classes of MHC molecules has not been compared previously. We have analyzed one such peptide, P18 from the V3 loop of HIV-1 gp160, which we have previously shown to be recognized by CD8(+) CTL with the class I molecule H-2D(d), and by CD4(+) Th cells with the class II molecule I-A(d). With the use of truncated and substituted peptides, we found that the minimal core peptides are very similar, that the residues required for class I binding precisely fit the recently identified consensus motif for peptides binding to D-d (XGPX[R/K/H]XXX(X)[L/I/F]), and that at least three of the same residues are involved in binding to class II I-A(d). In addition, several of the same residues are involved in TCR interaction when the peptide is presented by class I and class II molecules. Modeling shows results to be consistent with the crystal structure of a peptide-class II MHC complex. Thus, the recognition of this versatile peptide by CD4(+) Th cells with class II MHC molecules and by CD8(+) cytotoxic T cells with class I MHC molecules is remarkably similar in both the core peptide used and the role of different residues in the ternary complex. C1 NCI,MOLEC IMMUNOGENET & VACCINE RES SECT,METAB BRANCH,BETHESDA,MD 20892. NIAID,MOLEC BIOL SECT,IMMUNOL LAB,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,DEPT MED,DIV RHEUMATOL,BALTIMORE,MD 21201. NIPPON MED COLL,DEPT MICROBIOL & IMMUNOL,TOKYO,JAPAN. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 FU NIAID NIH HHS [AI 28718] NR 49 TC 81 Z9 81 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 FEB 15 PY 1995 VL 154 IS 4 BP 1973 EP 1986 PG 14 WC Immunology SC Immunology GA QG208 UT WOS:A1995QG20800049 PM 7530749 ER PT J AU WANG, AC BAX, A AF WANG, AC BAX, A TI REPARAMETRIZATION OF THE KARPLUS RELATION FOR (3)J(H-ALPHA-N) AND (3)J(H-N-C') IN PEPTIDES FROM UNIFORMLY C-13/N-15-ENRICHED HUMAN UBIQUITIN SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID COUPLING-CONSTANTS; NMR-SPECTROSCOPY; PROTEINS; RESOLUTION; SPECTRA; C-13 AB The Karplus relations for vicinal J couplings, which relate the peptide backbone angles phi and psi to (3)J(H(a)lpha-N) and (3)J(H-N-C'), have been reparametrized on the basis of measurements made on uniformly C-13/N-15-enriched human ubiquitin and backbone angles derived from the 1.8 Angstrom X-ray structure of this protein (Vijay-Kumar, S.; Bugg, C. E.; Cook, W. J. J. Mol. Biol. 1987, 194, 531-544). For (3)J(H(a)lpha-N), values measured using an E.COSY-type HCACO experiment fall in the -1.9 to 0.1 Hz range and are described by the following: (3)J(H(a)lpha-N) = -0.88 cos(2)(psi + 60 degrees) - 0.61 cos(psi + 60 degrees) - 0.27. The root-mean-square difference (rmsd) between measured values and the Karplus relation is 0.16 Hz. Values measured for (3)J(H-N-C') using an E.COSY-type HNCA experiment fall in the -0.4 to 3.6 Hz range, are described by 4.0 cos(2)(phi) + 1.1 cos(phi) + 0.1, and fit the observed J couplings with an rmsd of 0.45 Hz. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. NR 22 TC 77 Z9 77 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD FEB 15 PY 1995 VL 117 IS 6 BP 1810 EP 1813 DI 10.1021/ja00111a021 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA QG720 UT WOS:A1995QG72000021 ER PT J AU FENTON, RG LONGO, DL AF FENTON, RG LONGO, DL TI GENETIC INSTABILITY AND TUMOR-CELL VARIATION - IMPLICATIONS FOR IMMUNOTHERAPY SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID LYMPHOCYTES-T; MELANOMA-CELLS; SELECTIVE LOSS; COLON C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NR 24 TC 16 Z9 16 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 FEB 15 PY 1995 VL 87 IS 4 BP 241 EP 243 DI 10.1093/jnci/87.4.241 PG 3 WC Oncology SC Oncology GA QF716 UT WOS:A1995QF71600002 PM 7707413 ER PT J AU KESSLER, LG AF KESSLER, LG TI LUNG-CANCER RATES IN US MEN SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material RP KESSLER, LG (reprint author), NCI,APPL RES BRANCH,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD FEB 15 PY 1995 VL 87 IS 4 BP 251 EP 251 DI 10.1093/jnci/87.4.251 PG 1 WC Oncology SC Oncology GA QF716 UT WOS:A1995QF71600007 ER PT J AU SANDA, MG RESTIFO, NP WALSH, JC KAWAKAMI, Y NELSON, WG PARDOLL, DM SIMONS, JW AF SANDA, MG RESTIFO, NP WALSH, JC KAWAKAMI, Y NELSON, WG PARDOLL, DM SIMONS, JW TI MOLECULAR CHARACTERIZATION OF DEFECTIVE ANTIGEN-PROCESSING IN HUMAN PROSTATE-CANCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CLASS-II REGION; TUMOR-CELLS; GENE; MHC AB Background: Gene-modified tumor cell vaccines have shown efficacy in animal models of malignancy, including prostate cancer. Class I major histocompatibility complex (MHC) assembly and function in the cellular targets of such therapies is pivotal in determining the efficacy of specific cytokine-secreting tumor vaccines. Purpose: To help guide development of genetically engineered vaccine therapy for human prostate cancer, potential immune resistance pathways were evaluated by analysis of class I MHC assembly in prostate cancer cells. Method: Class I MHC assembly in metastasis-derived human prostate cancer cell lines (LNCaP, PPC-1, DU-145, PC-3, and TSU) and a normal prostate-derived cell line (TP-2) were characterized by phenotypic, molecular, and functional assays. Assembled class I MHC and antigen was measured by flow cytometry; mRNA levels of assembly components (class I MHC heavy chain, beta(2)-microglobulin, and the antigen transporter gene product TAP-2) were determined; and antigen processing was measured with a chimeric reconstituted system using vaccinia vectors. Restoration of antigen processing was attempted by interferon gamma stimulation and by transfection with mouse class I MHC heavy-chain cDNA. Results: Assembled class I MHC was underexpressed in two (LNCaP and PPC-1) of five prostate cancer cell lines compared with normal prostate-derived controls. PPC-1 cells underexpressed TAP-2 mRNA despite abundant class I MHC and beta(2)-microglobulin message. Induction of TAP-2 by interferon gamma indicated that coding sequences for TAP-2 message were present in PPC-1. Resistance to cytotoxic T lymphocytes (CTL) lysis showed a functional defect in antigen transport by PPC-1 cells; reversal of the molecular defect with interferon gamma led to restoration of functional antigen processing. In contrast, LNCaP cells had competent antigen transport but deficient class I MHC heavy-chain function despite abundant class I MHC RNA; though refractory to stimulation by interferon gamma, this defect responded to transfection of class I MHC heavy-chain cDNA. Conclusions: Metastatic prostate cancer cells can escape T-cell recognition via divergent mechanisms of defective class I MHC assembly. The specific underexpression of TAP-2 gene product in PPC-1 cells contrasts with prior studies of TAP gene underexpression in lung cancer (which concurrently underexpressed class I MHC heavy chain) and provides evidence for a regulatory pathway controlling TAP-2 gene expression in human cancers that may not affect class I MHC heavy-chain expression. Implications: In clinical application of gene therapy for prostate cancer, these findings provide a rationale for focusing on strategies that can circumvent sole reliance on class I MHC-mediated tumor cell recognition by CTL. C1 JOHNS HOPKINS UNIV,SCH MED,JAMES BUCHANAN BRADY UROL INST,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,CTR ONCOL,BALTIMORE,MD. NCI,DIV CANC TREATMENT,SURG BRANCH,BETHESDA,MD 20892. RI Restifo, Nicholas/A-5713-2008; Sanda, Martin/A-6202-2013; Kawakami, Yutaka /E-7429-2013; Sanda, Martin/B-2023-2015; OI Kawakami, Yutaka /0000-0003-4836-2855; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01]; NCI NIH HHS [CA01495, CA58236, P50 CA058236] NR 21 TC 167 Z9 167 U1 0 U2 6 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD FEB 15 PY 1995 VL 87 IS 4 BP 280 EP 285 DI 10.1093/jnci/87.4.280 PG 6 WC Oncology SC Oncology GA QF716 UT WOS:A1995QF71600012 PM 7707419 ER PT J AU ROSENBERG, SA AF ROSENBERG, SA TI TREATMENT OF PATIENTS WITH METASTATIC MELANOMA WITH AUTOLOGOUS TUMOR-INFILTRATING LYMPHOCYTES AND INTERLEUKIN-2 - RESPONSE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter RP ROSENBERG, SA (reprint author), NCI,BLDG 10,RM 2B44,BETHESDA,MD 20892, USA. NR 5 TC 4 Z9 4 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 FEB 15 PY 1995 VL 87 IS 4 BP 319 EP 319 DI 10.1093/jnci/87.4.319-a PG 1 WC Oncology SC Oncology GA QF716 UT WOS:A1995QF71600024 ER PT J AU IKARI, H SPANGLER, EL GREIG, NH PEI, XF BROSSI, A SPEER, D PATEL, N INGRAM, DK AF IKARI, H SPANGLER, EL GREIG, NH PEI, XF BROSSI, A SPEER, D PATEL, N INGRAM, DK TI MAZE-LEARNING IN AGED RATS IS ENHANCED BY PHENSERINE, A NOVEL ANTICHOLINESTERASE SO NEUROREPORT LA English DT Article DE CHOLINERGIC SYSTEM; MEMORY IMPAIRMENT; AGING; CHOLINOMIMETICS; PHYSOSTIGMINE ID CHOLINERGIC SYSTEM; CHOLINESTERASE INHIBITOR; MEMORY; PHYSOSTIGMINE; TETRAHYDROAMINOACRIDINE; DYSFUNCTION; IMPAIRMENT; DEMENTIA AB A new generation of cholinesterase inhibitors is expected to overcome some limitations of the therapeutic use of anticholinesterases. Phenserine is a long-acting and selective inhibitor of acetylcholinesterase with a preferential brain uptake. We have assessed the effects of chronic phenserine tartrate treatment on performance of aged Fischer-344 rats in the 14-unit T-maze. Phenserine (1-3 mg kg(-1), i.p.) treatment for 5 days significantly reduced the number of errors made in the Stone maze. Other performance variables were also improved. No side effects were noted across 5 days treatment at doses of 1-2 mg kg(-1). Phenserine can therefore improve the performance of aged rats in this complex maze task without producing obvious side effects. C1 NIA,GERONTOL RES CTR,HOPKINS BAYVIEW MED CTR,NATHAN W SHOCK LABS,MOLEC PHYSIOL & GENET SECT,BALTIMORE,MD 21224. NIA,NEUROSCI LAB,BETHESDA,MD 20892. GEORGETOWN UNIV,NATL INST HLTH,WASHINGTON,DC 20057. GEORGETOWN UNIV,DEPT CHEM,WASHINGTON,DC 20057. NR 27 TC 39 Z9 39 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD FEB 15 PY 1995 VL 6 IS 3 BP 481 EP 484 DI 10.1097/00001756-199502000-00019 PG 4 WC Neurosciences SC Neurosciences & Neurology GA QL154 UT WOS:A1995QL15400020 PM 7766848 ER PT J AU SCHMITT, JM AF SCHMITT, JM TI COMPACT IN-LINE INTERFEROMETER FOR LOW-COHERENCE REFLECTOMETRY SO OPTICS LETTERS LA English DT Article ID MICROSCOPE; TOMOGRAPHY; TISSUES AB An interferometer with an efficient confocal layout is described. Similar in structure to a folded Linnik microscope, the interferometer employs broadband illumination to improve rejection of out-of-focus light. A prototype reflectometry system based on the new interferometer achieved an axial resolution of less than 10 mu m within a probing depth of 1 mm in samples containing particulate scatterers and specularly reflecting objects. Options for mechanical and electronic scanning are discussed. RP SCHMITT, JM (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892, USA. NR 9 TC 8 Z9 8 U1 0 U2 1 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD FEB 15 PY 1995 VL 20 IS 4 BP 419 EP 421 DI 10.1364/OL.20.000419 PG 3 WC Optics SC Optics GA QG831 UT WOS:A1995QG83100025 PM 19859207 ER PT J AU KOLEY, AP ROBINSON, RC MARKOWITZ, A FRIEDMAN, FK AF KOLEY, AP ROBINSON, RC MARKOWITZ, A FRIEDMAN, FK TI INTERACTION OF POLYCYCLIC AROMATIC-HYDROCARBONS AND FLAVONES WITH CYTOCHROMES P450 IN THE ENDOPLASMIC-RETICULUM - EFFECT ON CO BINDING-KINETICS SO BIOCHEMISTRY LA English DT Article ID RAT-LIVER MICROSOMES; BETA-NAPHTHOFLAVONE; ALPHA-NAPHTHOFLAVONE; FLASH-PHOTOLYSIS; LIGAND-BINDING; 8 ISOZYMES; METABOLISM; PURIFICATION; HYDROXYLATION; ACTIVATION AB The flash photolysis technique was used to examine the kinetics of CO binding to cytochromes P450 in rat liver microsomes. The effect of polycyclic aromatic hydrocarbons (PAHs) and flavones was used to distinguish the kinetic behavior of the PAH-metabolizing P450 1A1 from that of the remaining multiple microsomal P450s. Applying this approach to microsomes from 3-methylcholanthrene-treated rats showed that although all tested PAHs accelerated CO binding to P450 1A1, the extent varied markedly for different PAHs. The tricyclic PAHs phenanthrene and anthracene enhanced CO binding by 37- and 49-fold, respectively, while several tetracyclic and pentacyclic PAHs increased the rate by 3-16-fold. The results indicate that PAHs exert a dual effect on the rate of CO binding to P450 1A1: a general enhancement via widening of the CO access channel and a reduction that is dependent on PAH size. Although 5,6-benzoflavone increased the rate of CO binding to P450 1A1 by 3.5-fold, it additionally decelerated binding to a constitutive P450 by 15-fold. This flavone thus exerts markedly different effects on two P450s within the same microsomal sample. In contrast, the sole effect of 7,8-benzoflavone was acceleration of CO binding to P450 1A1 by 18-fold. The divergent effects of these isomeric flavones, which only differ in positioning of an aromatic ring, illustrate the sensitivity of CO binding to substrate structure. The varying effects of these PAHs and flavones on CO binding kinetics show that they differentially modulate P450 conformation and access of ligands to the P450 heme and demonstrate that binding of carcinogens to a specific target P450 can be evaluated in its native microsomal milieu. C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RI Friedman, Fred/D-4208-2016 NR 40 TC 11 Z9 11 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 14 PY 1995 VL 34 IS 6 BP 1942 EP 1947 DI 10.1021/bi00006a015 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QG848 UT WOS:A1995QG84800015 PM 7849053 ER PT J AU MAO, SY YAMASHITA, T METZGER, H AF MAO, SY YAMASHITA, T METZGER, H TI CHEMICAL CROSS-LINKING OF IGE-RECEPTOR COMPLEXES IN RBL-2H3 CELLS SO BIOCHEMISTRY LA English DT Article ID BASOPHILIC LEUKEMIA-CELLS; PROTEIN-TYROSINE KINASE; FC-EPSILON-RI; TUMOR MAST-CELLS; IMMUNOGLOBULIN-E; HIGH-AFFINITY; SIGNAL TRANSDUCTION; ANTIGEN RECEPTOR; ALPHA-SUBUNIT; BETA-SUBUNIT AB Aggregation of the high-affinity receptors for IgE (FC epsilon RI) on mast cells activates nonreceptor kinases and other enzymes, thereby initiating a complex biochemical cascade. We have employed a chemical cross-linker in order to stabilize the association of Fc epsilon RI with other cellular proteins that are involved in the early events. We reacted the water-soluble, membrane-impermeant chemical cross-linker 3,3'-dithiobis(sulfosuccinimidyl propionate) (DTSSP) with permeabilized rat mucosal mast cells of the RBL line and analyzed immunoprecipitates of the receptor in detergent lysates of cells that had biosynthetically incorporated [S-35]cysteine. Gel electrophoresis revealed substantial amounts of nonreceptor components only when the cells had been reacted with DTSSP. Receptors isolated from cells whose receptor-bound IgE had been aggregated with antigen prior to cross-linking yielded a similar pattern of S-35-labeled proteins. However, when the cells had also been exposed to [gamma-P-32]ATP, the proteins associated with the cross-linked, aggregated receptors revealed enhanced incorporation of P-32 compared to those associated with cross-linked, unaggregated receptors. A variety of antibodies were used to try to identify the associated proteins. Of those tested for, two, the src-like kinase p53/56(lyn) and the delta isoform of protein kinase C, were associated with the cross-linked Fc epsilon RI in amounts much greater than could be accounted for by nonspecific cross-linking. RP MAO, SY (reprint author), NIAMSD,ARTHRITIS & RHEUMAT BRANCH,CHEM IMMUNOL SECT,BETHESDA,MD 20892, USA. NR 46 TC 11 Z9 11 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 14 PY 1995 VL 34 IS 6 BP 1968 EP 1977 DI 10.1021/bi00006a018 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QG848 UT WOS:A1995QG84800018 PM 7531496 ER PT J AU BAGROV, AY ROUKOYATKINA, NI PINAEV, AG DMITRIEVA, RI FEDOROVA, OV AF BAGROV, AY ROUKOYATKINA, NI PINAEV, AG DMITRIEVA, RI FEDOROVA, OV TI EFFECTS OF 2 ENDOGENOUS NA+,K+-ATPASE INHIBITORS, MARINOBUFAGENIN AND OUABAIN, ON ISOLATED RAT AORTA SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE NA+,K+-ATPASE; BUFODIENOLIDE; MARINOBUFAGENIN; OUABAIN; SMOOTH MUSCLE, VASCULAR; VASOCONSTRICTION ID SPONTANEOUSLY HYPERTENSIVE RATS; ACUTE MYOCARDIAL-ISCHEMIA; DIGITALIS-LIKE FACTORS; DIGOXIN-LIKE FACTOR; REDUCED RENAL MASS; PUMP ACTIVITY; HUMAN-PLASMA; K+-PUMP; NA+; ARTERIES AB Previously, we reported that the venom of Bufo marinus toad contains a Na+,K+-ATPase inhibitor with potent vasoconstrictor activity. In the present study, using thin-layer chromatography in Silicagel 60 F-254+366, we separated a vasoactive substance from a mixture of steroids from Bufo marinus venom. Based on chromatographic mobility of this substance and typical color reaction after its vizualization with SbCl3, we identified it as a previously described steroid, marinobufagenin. Vasoconstrictor and Na+,K+ pump inhibitory properties of marinobufagenin were studied in isolated rat aortic rings and compared with those of ouabain. Ouabain (10-100 mu mol.l(-1)) produced weak vasoconstriction, which was blocked by 2 mu mol.l(-1) phentolamine. 10 mu mol.l(-1) ouabain stimulated, and at higher concentrations inhibited, the Na+,K+ pump. 2 mu mol.l(-1) phentolamine abolished the activating effect of 10 mu mol.l(-1) ouabain on the Na+,K+ pump, but did not alter the inhibitory action of higher concentrations of ouabain. By contrast, marunibufagenin elicited rapid and strong vasoconstriction and inhibited ouabain-sensitive Rb-86 uptake. Antidigoxin antibody antagonized the vasoconstrictor responses to marinobufagenin, but not to ouabain. 2 mu mol.l(-1) phentolamine did not alter the constrictor effect of marinobufagenin. In solid-phase digoxin immunoassay, marinobufagenin demonstrated higher digoxin-like immunoreactivity than ouabain. C1 RUSSIAN ACAD SCI,IM SECHENOV INST EVOLUT PHYSIOL & BIOCHEM,PHARMACOL LAB,ST PETERSBURG 194223,RUSSIA. RP BAGROV, AY (reprint author), NIA,GERONTOL RES CTR,BEHAV SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 49 TC 52 Z9 52 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 FEB 14 PY 1995 VL 274 IS 1-3 BP 151 EP 158 DI 10.1016/0014-2999(94)00735-P PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QH200 UT WOS:A1995QH20000020 PM 7768267 ER PT J AU WU, YM SIFRI, CD LEI, HH SU, XZ WELLEMS, TE AF WU, YM SIFRI, CD LEI, HH SU, XZ WELLEMS, TE TI TRANSFECTION OF PLASMODIUM-FALCIPARUM WITHIN HUMAN RED-BLOOD-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MALARIA; CHLORAMPHENICOL ACETYLTRANSFERASE; GENE EXPRESSION; CODON USAGE ID HUMAN MALARIA PARASITES; CHLOROQUINE-RESISTANCE; TOXOPLASMA-GONDII; EXPRESSION; GENOME; GENES; PYRIMETHAMINE; SEQUENCES; CULTURE; CROSS AB Plasmodium falciparum malaria parasites within human red blood cells (RBCs) have been successfully transfected to produce chloramphenicol acetyltransferase (CAT). Electroporation of parasitized RBCs was used to introduce plasmids that have CAT-encoding DNA flanked by 5' and 3' untranslated sequences of the P. falciparum hsp86, hrp3, and hrp2 genes. These flanking sequences were required for expression as their excision abolished CAT activity in transfected parasites. Transfection signals from native CAT-encoding DNA compared well with those from a synthetic DNA sequence adapted to the P. falciparum major codon bias, demonstrating effective expression of the bacterial sequence despite its use of rare P. falciparum codons. Transfected ring-stage parasites produced CAT signals at least as strong as transfected schizont-stage parasites even though ring stages are surrounded by more RBC cytoplasm than schizonts. The transfection of erythrocyte-stage P. falciparum parasites advances our ability to pursue genetic analysis of this major pathogen. RP WU, YM (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. OI Su, Xinzhuan/0000-0003-3246-3248 NR 26 TC 265 Z9 273 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 14 PY 1995 VL 92 IS 4 BP 973 EP 977 DI 10.1073/pnas.92.4.973 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QG770 UT WOS:A1995QG77000009 PM 7862676 ER PT J AU NIELSEN, S CHOU, CL MARPLES, D CHRISTENSEN, EI KISHORE, BK KNEPPER, MA AF NIELSEN, S CHOU, CL MARPLES, D CHRISTENSEN, EI KISHORE, BK KNEPPER, MA TI VASOPRESSIN INCREASES WATER PERMEABILITY OF KIDNEY COLLECTING DUCT BY INDUCING TRANSLOCATION OF AQUAPORIN-CD WATER CHANNELS TO PLASMA-MEMBRANE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NEPHROGENIC DIABETES-INSIPIDUS; RAT-KIDNEY; RENAL TUBULES; COATED PITS; IDENTIFICATION; LOCALIZATION; ENDOCYTOSIS; PROTEINS; CLONING; BLADDER AB Water excretion by the kidney is regulated by the peptide hormone vasopressin, Vasopressin increases the water permeability of the renal collecting duct cells, allowing more water to be reabsorbed from collecting duct urine to blood. Despite long-standing interest in this process, the mechanism of the water permeability increase has remained undetermined. Recently, a molecular water channel (AQP-CD) has been cloned whose expression appears to be limited to the collecting duct. Previously, we immunolocalized this water channel to the apical plasma membrane (APM) and to intracellular vesicles (IVs) of collecting duct cells. Here, we test the hypothesis that vasopressin increases cellular water permeability by inducing exocytosis of AQP-CD-laden vesicles, transferring water channels from IVs to APM. Rat collecting ducts were perfused in vitro to determine water permeability and subcellular distribution of AQP-CD in the same tubules. The collecting ducts were fixed for immunoelectron microscopy before, during, and after exposure to vasopressin. Vasopressin exposure induced increases in water permeability and the absolute labeling density of AQP-CD in the APM. In parallel, the APM:IV labeling ratio increased. Furthermore, in response to vasopressin withdrawal, AQP-CD labeling density in the APM and the APM:IV labeling ratio decreased in parallel to a measured decrease in osmotic water permeability. We conclude that vasopressin increases the water permeability of collecting duct cells by inducing a reversible translocation of AQP-CD water channels from IVs to the APM. C1 NHLBI, KIDNEY & ELECTROLYTE METAB LAB, BETHESDA, MD 20892 USA. AARHUS UNIV, DEPT CELL BIOL, DK-8000 AARHUS C, DENMARK. NR 34 TC 696 Z9 711 U1 4 U2 29 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 14 PY 1995 VL 92 IS 4 BP 1013 EP 1017 DI 10.1073/pnas.92.4.1013 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QG770 UT WOS:A1995QG77000017 PM 7532304 ER PT J AU KOBAYASHI, K MORITA, S SAWADA, H MIZUGUCHI, T YAMADA, K NAGATSU, I FUJITA, K KREITMAN, RJ PASTAN, I NAGATSU, T AF KOBAYASHI, K MORITA, S SAWADA, H MIZUGUCHI, T YAMADA, K NAGATSU, I FUJITA, K KREITMAN, RJ PASTAN, I NAGATSU, T TI IMMUNOTOXIN-MEDIATED CONDITIONAL DISRUPTION OF SPECIFIC NEURONS IN TRANSGENIC MICE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE RECOMBINANT IMMUNOTOXIN; DOPAMINE BETA-HYDROXYLASE; INTERLEUKIN 2 RECEPTOR; CELL ABLATION ID NOREPINEPHRINE-CONTAINING AFFERENTS; INTERLEUKIN-2 RECEPTOR; CHRONIC PARKINSONISM; PURKINJE CELLS; RAT CEREBELLUM; TOXIN GENE; EXPRESSION; ABLATION; DOPAMINE; REGION AB We have developed a transgenic approach, termed immunotoxin-mediated cell targeting (IMCT), to ablate conditionally selective neurons in the brain with the cytotoxic activity of immunotoxins. Transgenic mice were created that express the human interleukin 2 receptor alpha subunit (IL-2R alpha) under the control of the dopamine beta-hydroxylase (DBH) gene promoter. The animals were treated intracerebroventricularly with a recombinant immunotoxin, anti-Tac(Fv)-PE40, which selectively kills animal cells bearing human IL-2R alpha. The immunotoxin caused a characteristic behavioral abnormality only in the transgenic mice. This was accompanied by a dramatic loss of DBH-containing neurons and a significant decrease in DBH activity and norepinephrine levels in various regions of the brain. IMCT should provide a general technique to create animal models of human neurodegenerative disorders by targeting neurons or other cell types. C1 FUJITA HLTH UNIV,SCH MED,INST COMPREHENS MED SCI,TOYOAKE,AICHI 47011,JAPAN. FUJITA HLTH UNIV,SCH MED,DEPT ANAT,TOYOAKE,AICHI 47011,JAPAN. CHUBU NATL HOSP,DEPT CLIN RES,OBU 474,JAPAN. NCI,DIV CANC BIOL,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 28 TC 63 Z9 65 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 14 PY 1995 VL 92 IS 4 BP 1132 EP 1136 DI 10.1073/pnas.92.4.1132 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QG770 UT WOS:A1995QG77000042 PM 7862648 ER PT J AU KUTTY, RK KUTTY, G WIGGERT, B CHADER, GJ DARROW, RM ORGANISCIAK, DT AF KUTTY, RK KUTTY, G WIGGERT, B CHADER, GJ DARROW, RM ORGANISCIAK, DT TI INDUCTION OF HEME OXYGENASE-1 IN THE RETINA BY INTENSE VISIBLE-LIGHT - SUPPRESSION BY THE ANTIOXIDANT DIMETHYLTHIOUREA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN-SKIN FIBROBLASTS; RAT RETINA; BILIVERDIN REDUCTASE; GLUTATHIONE LEVELS; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; UVA RADIATION; ALBINO-RATS; EXPRESSION; DAMAGE AB The effect of intense visible light (light damage) on the expression of heme oxygenase 1 (HO-1), a protein induced by oxidative stress, was investigated in the rat retina. A sensitive reverse transcription-PCR assay demonstrated the expression of mRNA for HO-1 as well as HO-2, the noninducible HO form, in the normal retina, As analyzed by Northern blotting, however, HO-1 mRNA was barely detectable under normal circumstances, After exposure to intense visible light, retinas had markedly higher HO-1 mRNA levels than unexposed controls, with increases up to 52- and 98-fold at 12 and 24 hr of exposure, respectively Intense light exposure also resulted in an increase in HO-1 protein, In contrast, no appreciable change in HO-2 mRNA or protein was observed, The increase in HO-1 message was more pronounced in rats previously reared in the dark than in those reared in a weak cyclic-light environment. A marked decrease from the high level of HO-1 mRNA induced by light insult was observed when the animals were allowed to recover in the dark for 24 hr after light exposure, Most important, treatment of animals with 1,3-dimethylthiourea, a synthetic antioxidant, prior to light exposure effectively blocked the increase in HO-1 mRNA, Thus, HO-1 is a sensitive marker for assessing light-induced insult in the retina, Since increased expression of HO-1 is thought to be a cellular defense against oxidative damage, its expression may play an important role in protecting the retina against tight damage. C1 WRIGHT STATE UNIV,DEPT BIOCHEM & MOLEC BIOL,DAYTON,OH 45435. RP KUTTY, RK (reprint author), NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892, USA. FU NEI NIH HHS [EY01959] NR 46 TC 117 Z9 117 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 14 PY 1995 VL 92 IS 4 BP 1177 EP 1181 DI 10.1073/pnas.92.4.1177 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QG770 UT WOS:A1995QG77000051 PM 7862656 ER PT J AU ESTABROOKS, LL BREG, WR HAYDEN, MR LEDBETTER, DH MYERS, RM WYANDT, HE YANGFENG, TL HIRSCHHORN, K AF ESTABROOKS, LL BREG, WR HAYDEN, MR LEDBETTER, DH MYERS, RM WYANDT, HE YANGFENG, TL HIRSCHHORN, K TI SUMMARY OF THE 1993 ASHG ANCILLARY MEETING - RECENT RESEARCH ON CHROMOSOME-4P SYNDROMES AND GENES SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Editorial Material DE CHROMOSOME 4P; REVIEW; WOLF-HIRSCHHORN SYNDROME ID WOLF-HIRSCHHORN SYNDROME; HUNTINGTON DISEASE REGION; ALPHA-ADDUCIN GENE; PRENATAL-DIAGNOSIS; CANDIDATE REGION; PARTIAL DELETION; SHORT ARM; CLONING; TRANSLOCATION; ORIGIN AB The following is a summary of presentations given during an ancillary meeting to the 1993 American Society of Human Genetics Meeting in New Orleans, LA. This ancillary meeting, entitled ''Recent Research on Chromosome 4p Syndromes and Genes,'' reviewed the history of the Wolf-Hirschhorn syndrome (WHS), the natural history of patients with WHS, and the smallest region of deletion associated with the WHS. The proximal 4p deletion syndrome and the duplication 4p syndrome were also described and advice was offered regarding detection of chromosome 4p deletions, duplications, and rearrangements. The current status of the physical map of chromosome 4p with emphasis on the genes that map to the 4p16 region was presented along with a preliminary phenotypic map of 4p16. The goal of this format was to provide a comprehensive review of the clinical presentations, diagnostic capabilities, and genetic mapping advances involving chromosome 4p. (C) 1995 Wiley-Liss, Inc. C1 SMITHKLINE BEECHAM CLIN LABS,VAN NUYS,CA. STANFORD UNIV,SCH MED,DEPT GENET,STANFORD,CA 94305. YALE UNIV,SCH MED,DEPT HUMAN GENET,NEW HAVEN,CT 06510. UNIV BRITISH COLUMBIA,DEPT MED GENET,VANCOUVER,BC,CANADA. NATL CTR HUMAN GENOME RES,BETHESDA,MD. BOSTON UNIV,DEPT BIOL,BOSTON,MA 02215. BOSTON UNIV,DEPT PEDIAT,BOSTON,MA 02215. BOSTON UNIV,CTR HUMAN GENET,BOSTON,MA 02215. SCH MED BOSTON,BOSTON,MA. CUNY MT SINAI SCH MED,DEPT PEDIAT,NEW YORK,NY 10029. RI Hayden, Michael/D-8581-2011 OI Hayden, Michael/0000-0001-5159-1419 NR 42 TC 25 Z9 25 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD FEB 13 PY 1995 VL 55 IS 4 BP 453 EP 458 DI 10.1002/ajmg.1320550412 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA QJ324 UT WOS:A1995QJ32400011 PM 7762585 ER PT J AU KARNI, A AF KARNI, A TI WHEN PRACTICE MAKES PERFECT SO LANCET LA English DT Letter RP KARNI, A (reprint author), NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892, USA. NR 5 TC 17 Z9 17 U1 1 U2 3 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0099-5355 J9 LANCET JI Lancet PD FEB 11 PY 1995 VL 345 IS 8946 BP 395 EP 395 DI 10.1016/S0140-6736(95)90386-0 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA QF722 UT WOS:A1995QF72200064 PM 7845149 ER PT J AU KUPRASH, DV RICE, NR NEDOSPASOV, SA AF KUPRASH, DV RICE, NR NEDOSPASOV, SA TI HOMODIMER OF P50(NF-KAPPA-B1) DOES NOT INTRODUCE A SUBSTANTIAL DIRECTED BEND INTO DNA ACCORDING TO 3 DIFFERENT EXPERIMENTAL ASSAYS SO NUCLEIC ACIDS RESEARCH LA English DT Article ID NF-KAPPA-B; GROUP PROTEIN HMG-I(Y); CRYSTAL-STRUCTURE; OPPOSITE ORIENTATIONS; TRANSCRIPTION FACTORS; IMMUNOGLOBULIN-KAPPA; BINDING SUBUNIT; HELICAL REPEAT; COMPLEX; FLEXIBILITY AB Transcription factors can distort the conformation of the DNA double helix upon binding to their target sites. Previously, studies utilizing circular permutation-electrophoretic mobility shift assay suggested that the homodimer of p50 (NF kappa B1), canonical NF-kappa B (p65-p50), as well as several non-canonical NF-kappa B/Rel complexes, may induce substantial DNA bending at the binding site. Here we have applied three additional experimental approaches, helical phasing analysis, minicircle binding and cyclization kinetics, and conclude that the homodimer of p50 introduces virtually no directed bend into the consensus kappa B sequences GGGACTTTCC or GGGAATTCCC. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. RUSSIAN ACAD SCI,ENGELHARDT INST MOLEC BIOL,CYTOKINE MOLEC BIOL LAB,MOSCOW 117984,RUSSIA. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Kuprash, Dmitry/O-4899-2015; Nedospasov, Sergei/Q-7319-2016 OI Kuprash, Dmitry/0000-0002-1488-4148; FU NCI NIH HHS [N01-CO-74101] NR 48 TC 17 Z9 17 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB 11 PY 1995 VL 23 IS 3 BP 427 EP 433 DI 10.1093/nar/23.3.427 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QK646 UT WOS:A1995QK64600017 PM 7885838 ER PT J AU SAX, CM CVEKL, A KANTOROW, M GOPALSRIVASTAVA, R ILAGAN, JG AMBULOS, NP PIATIGORSKY, J AF SAX, CM CVEKL, A KANTOROW, M GOPALSRIVASTAVA, R ILAGAN, JG AMBULOS, NP PIATIGORSKY, J TI LENS-SPECIFIC ACTIVITY OF THE MOUSE ALPHA-A-CRYSTALLIN PROMOTER IN THE ABSENCE OF A TATA BOX - FUNCTIONAL AND PROTEIN-BINDING ANALYSIS OF THE MOUSE ALPHA-A-CRYSTALLIN PE1 REGION SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MAJOR LATE PROMOTER; HEAT-SHOCK PROTEIN; RNA POLYMERASE-II; TRANSCRIPTION FACTOR; CHLORAMPHENICOL ACETYLTRANSFERASE; EPITHELIAL-CELLS; TRANSGENIC MICE; COOPERATIVE INTERACTION; MAMMALIAN-CELLS; GENE-EXPRESSION AB Lens-specific expression of the mouse alpha A-crystallin gene is regulated at the level of transcription. Here, we have studied the role of the PE1 region, which contains the TATA box (-31/-26) and the immediately adjacent PE1B sequence (-25/-12), in transcriptional regulation. Deletions within either the TATA box or PE1B sequence eliminated promoter activity in transfected lens cells. Surprisingly, these deletions did not eliminate lens-specific promoter activity of the transgene of transgenic mice. Transcription of the transgene with a TATA-deleted promoter initiated at multiple sites in the lenses of the transgenic mice. Footprint analysis revealed that the entire PE1 region was protected by nuclear extracts prepared from lens cells which express the alpha A-crystallin gene and from fibroblasts which do not express the gene. The -37/+3 region formed three specific EMSA complexes using lens cell nuclear extracts, while a similar but much less intense pattern was observed when a fibroblast nuclear extract was used. Competition experiments indicated that these complexes were not due to the binding of TBP to the TATA box, but rather to the binding of other nuclear proteins to the PE1B -25/-19 region. A series of co-transfection competition studies in vivo also suggested the functional importance of proteins binding in the -25/-19 region. The PE1B protein-DNA interactions appear to be conserved in the chicken, rodent and human alpha A-crystallin gene as well as within the alpha A-and alpha B-crystallin genes in the mouse. Our findings indicate that the PE1B region is important for mouse alpha A-crystallin promoter activity; the proximity of this site to the TATA box raises the possibility for cooperativity or competition between TBP and PE1B-bound proteins. C1 UNIV MARYLAND,SCH MED,HOWARD HUGHES MED INST,RES SCHOLARS PROGRAM,BALTIMORE,MD 21202. UNIV MARYLAND,SCH MED,DEPT MICROBIOL & IMMUNOL,BALTIMORE,MD 21202. RP SAX, CM (reprint author), NEI,MOLEC & DEV BIOL LAB,BLDG 6,ROOM 208,BETHESDA,MD 20892, USA. RI Cvekl, Ales/B-2427-2013 NR 76 TC 18 Z9 19 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB 11 PY 1995 VL 23 IS 3 BP 442 EP 451 DI 10.1093/nar/23.3.442 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QK646 UT WOS:A1995QK64600019 PM 7885839 ER PT J AU WOODFORD, K WEITZMANN, MN USDIN, K AF WOODFORD, K WEITZMANN, MN USDIN, K TI THE USE OF K+-FREE BUFFERS ELIMINATES A COMMON-CAUSE OF PREMATURE CHAIN TERMINATION IN PCR AND PCR SEQUENCING SO NUCLEIC ACIDS RESEARCH LA English DT Article C1 NIDDKD,GENOM STRUCT & FUNCT SECT,BETHESDA,MD 20892. NR 4 TC 16 Z9 16 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB 11 PY 1995 VL 23 IS 3 BP 539 EP 539 DI 10.1093/nar/23.3.539 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QK646 UT WOS:A1995QK64600034 PM 7885853 ER PT J AU DIWAN, BA HENNEMAN, JR RICE, JM AF DIWAN, BA HENNEMAN, JR RICE, JM TI FURTHER EVIDENCE FOR PROMOTER-DEPENDENT DEVELOPMENT OF HEPATOBLASTOMA IN THE MOUSE SO CANCER LETTERS LA English DT Article DE HEPATOBLASTOMA; HEPATOCELLULAR TUMORS; INITIATION; PROMOTION; PROGRESSION ID MICE AB In previous studies, we found that male D2B6F1 mice fed phenobarbital (PB) for 53 weeks following N-nitrosodiethylamine (NDEA) initiation developed a high (70-80%) incidence of malignant hepatoblastomas. A very low (3.3%) incidence of such tumors occurred in the absence of promoter treatment in NDEA-initiated mice observed for 60 weeks, although nearly 50% of these animals developed hepatocellular lesions. To investigate whether hepatocellular lesions in NDEA-initiated mice or spontaneous hepatocellular lesions promoted by PB in mice given PB but no NDEA, progress to hepatoblastomas later in life, mice exposed to NDEA alone and PB alone were maintained for 110 weeks, Hepatocellular tumors (adenomas and carcinomas) occurred in almost all (97%) mice given NDEA alone. However, only 10% of NDEA-treated mice developed hepatoblastomas. Thus, despite its ability to induce hepatocellular neoplasms, NDEA treatment alone was rarely sufficient to induce hepatoblastomas in these mice. In contrast, PB treatment in the absence of NDEA initiation promoted the development of spontaneously occurring hepatocellular lesions, a significant number (37%) of which progressed to hepatoblastomas. Our observations clearly show that in this animal model the development of hepatoblastoma from its precursor cells (hepatocellular adenoma and carcinoma cells) occurs predominantly in the presence of promoting agents such as PB. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RP DIWAN, BA (reprint author), PROGRAM RESOURCES INC,DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21701, USA. NR 17 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD FEB 10 PY 1995 VL 89 IS 1 BP 29 EP 35 DI 10.1016/0304-3835(95)90154-X PG 7 WC Oncology SC Oncology GA QP339 UT WOS:A1995QP33900005 PM 7882299 ER PT J AU ANDERSON, DM JOHNSON, L GLACCUM, MB COPELAND, NG GILBERT, DJ JENKINS, NA VALENTINE, V KIRSTEIN, MN SHAPIRO, DN MORRIS, SW GRABSTEIN, K COSMAN, D AF ANDERSON, DM JOHNSON, L GLACCUM, MB COPELAND, NG GILBERT, DJ JENKINS, NA VALENTINE, V KIRSTEIN, MN SHAPIRO, DN MORRIS, SW GRABSTEIN, K COSMAN, D TI CHROMOSOMAL ASSIGNMENT AND GENOMIC STRUCTURE OF IL15 SO GENOMICS LA English DT Article ID CELL GROWTH-FACTOR; GM-CSF; HUMAN IL-3; RECEPTOR; GENE; HEMATOPOIETIN; ORGANIZATION; CLONING AB Interleukin-15 (IL-15) is a novel cytokine whose effects on T-cell activation and proliferation are similar to those of interleukin-2 (IL-2), presumably because IL-15 utilizes the beta and gamma chains of the IL-2 receptor. Murine IL-15 cDNA and genomic clones were isolated and characterized. The murine Il15 gene was found to consist of eight exons spanning at least 34 kb and was localized to the central region of mouse chromosome 8 by interspecific backcross analysis. Intron positions in a partial human IL15 genomic clone were identical with positions of corresponding introns in the murine gene. The human IL15 gene was mapped to human chromosome 4q31 by fluorescence in situ hybridization. (C) 1995 Academic Press, Inc. C1 NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, MAMMALIAN GENET LAB, FREDERICK, MD 21702 USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38101 USA. RP ANDERSON, DM (reprint author), IMMUNEX RES & DEV CORP, 51 UNIV ST, SEATTLE, WA 98101 USA. FU NCI NIH HHS [N01-CO-74101, CA01702, CA21765] NR 21 TC 90 Z9 95 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD FEB 10 PY 1995 VL 25 IS 3 BP 701 EP 706 DI 10.1016/0888-7543(95)80013-C PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA QL416 UT WOS:A1995QL41600013 PM 7759105 ER PT J AU HUPPI, K SIWARSKI, D PISEGNA, JR WANK, S AF HUPPI, K SIWARSKI, D PISEGNA, JR WANK, S TI CHROMOSOMAL LOCALIZATION OF THE GASTRIC AND BRAIN RECEPTORS FOR CHOLECYSTOKININ (CCKAR AND CCKBR) IN HUMAN AND MOUSE SO GENOMICS LA English DT Note ID FUNCTIONAL EXPRESSION; B RECEPTOR; MOLECULAR-CLONING; RAT PANCREAS; ANTAGONIST; GENE; LINKAGE; POTENT AB Receptors for cholcystokinin (CCK) can be pharmacologically classified into at least two distinct subtypes, CCK(A)R and CCK(B)R. In an effort to determine whether the CCKA and CCKB receptors may be associated with certain CNS or gastrointestinal diseases, we have localized and compared the human and mouse chromosomal loci encoded by the CCKAR and CCKBR genes. The gene encoding the CCKA receptor maps to a syntenic region of human chromosome 4 and mouse chromosome 5. The CCKB receptor gene, on the other hand, resides on a syntenic region of human chromosome 11 and distal mouse chromosome 7. Localization of the CCK receptors with two dopamine receptors, DRD5 (4p15.1-p15.3) and DRD4 (11p15), provides the interesting possibility of coinvolvement in neuropsychiatric or CNS illnesses. (C) 1995 Academic Press, Inc. C1 NIDDK,DIGEST DIS BRANCH,BETHESDA,MD 20892. RP HUPPI, K (reprint author), NCI,GENET LAB,MOLEC GENET SECT,BLDG 37,BETHESDA,MD 20892, USA. NR 25 TC 35 Z9 35 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD FEB 10 PY 1995 VL 25 IS 3 BP 727 EP 729 DI 10.1016/0888-7543(95)80018-H PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA QL416 UT WOS:A1995QL41600018 PM 7759110 ER PT J AU ZULLO, S UPENDER, M AF ZULLO, S UPENDER, M TI RAT KARYOTYPING BY FLUORESCENCE IN-SITU HYBRIDIZATION (FISH) - LOCALIZATION OF ONCOGENE C-RAF TO 4Q42, RETINOBLASTOMA ANTIONCOGENE TO 15Q12, AND MITOCHONDRIAL D-LOOP-LIKE SEQUENCES TO THE Y-CHROMOSOME SO GENOMICS LA English DT Note ID INSITU HYBRIDIZATION; GENE; GENOME; PROBES; MOUSE; ALU; DNA AB Fluorescence in situ hybridization (FISH) has been used to karyotype the rat genome with long interspersed repetitive elements (LINEs). Two-color FISH experiments were used to localize the rat c-raf oncogene to 4q42 and the rat retinoblastoma anti-oncogene to 15q12. In addition, sequences similar to the rat mitochondrial origin of replication (D-loop-like sequences) have been found to be concentrated among repetitive element sequences on the Y chromosome. This report extends hybridization-based karyotype technology to the rat, thus facilitating the application of FISH to rat gene mapping. (C) 1995 Academic Press, Inc. C1 NIMH,CTR NEUROSCI,BIOCHIM GENET LAB,WASHINGTON,DC 20032. RP ZULLO, S (reprint author), YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06510, USA. NR 13 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD FEB 10 PY 1995 VL 25 IS 3 BP 753 EP 756 DI 10.1016/0888-7543(95)80026-I PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA QL416 UT WOS:A1995QL41600026 PM 7759118 ER PT J AU RYU, S RAMSEIER, TM MICHOTEY, V SAIER, MH GARGES, S AF RYU, S RAMSEIER, TM MICHOTEY, V SAIER, MH GARGES, S TI EFFECT OF THE FRUR REGULATOR ON TRANSCRIPTION OF THE PTS OPERON IN ESCHERICHIA-COLI SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BACTERIAL PHOSPHOTRANSFERASE SYSTEM; CAMP RECEPTOR PROTEIN; SALMONELLA-TYPHIMURIUM; NUCLEOTIDE-SEQUENCE; POSITIVE REGULATION; MOLECULAR-CLONING; 2 PROMOTERS; CRR GENES; FRUCTOSE; PHOSPHOENOLPYRUVATE AB The promoters of the pts operon of Escherichia coli are controlled by the cyclic AMP receptor protein (CRP) complexed with cAMP (CRP.cAMP). In addition, glucose stimulates pts operon expression in vivo. The pts promoter region has a fructose repressor (FruR)-binding site (the FruR box) that partially overlaps with one of the CRP.cAMP-binding sites. The effects of the pleiotropic transcriptional regulator FruR on pfs operon expression were studied to determine whether the in vivo glucose effect on pts operon expression is mediated by FruR. In vitro, FruR can repress P1b transcription, which is activated by CRP.cAMP, and restore P1a transcription, which is repressed by CRP.cAMP. FruR can displace CRP cAMP from its binding site in the presence of RNA polymerase even though FruR and CRP.cAMP can bind simultaneously to their partially overlapping binding sites in the absence of RNA polymerase. FruR had very little effect on the transcription of the P0 promoter, which is most important for regulation by glucose. Consistent with the in vitro results, pts P0 transcription did not increase as much In cells grown in the presence of fructose or in fruR(-) mutant cells as in cells grown in the presence of glucose. These results suggest that FruR alone does not mediate the in vivo glucose effect on pts operon expression. C1 NCI, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. UNIV CALIF SAN DIEGO, DEPT BIOL, LA JOLLA, CA 92093 USA. NR 37 TC 33 Z9 33 U1 1 U2 3 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 FEB 10 PY 1995 VL 270 IS 6 BP 2489 EP 2496 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QF535 UT WOS:A1995QF53500017 PM 7852310 ER PT J AU IZUTA, S ROBERTS, JD KUNKEL, TA AF IZUTA, S ROBERTS, JD KUNKEL, TA TI REPLICATION ERROR RATES FOR G-CENTER-DOT-DGTP, T-CENTER-DOT-DGTP, AND A-CENTER-DOT-DGTP MISPAIRS AND EVIDENCE FOR DIFFERENTIAL PROOFREADING BY LEADING AND LAGGING-STRAND DNA-REPLICATION COMPLEXES IN HUMAN-CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID UV-IRRADIATED DNA; FRAMESHIFT FIDELITY; POLYMERASE; INVITRO; ALPHA; EXONUCLEASE; EXTRACTS; DELTA AB We have determined the fidelity of DNA replication by human cell extracts in reactions containing excess dGTP, Replication errors were scored using two M13 DNA substrates having the replication origin on opposite sides of the lacZ alpha-complementation gene, The data suggest that the average rates for replication errors resulting from G(template), T(.)dGTP, and A(.)dGTP mispairs are 25 x 10(-6), 12 x 10(-6), and 3 x 10(-6), respectively. The data also suggest that error rates for both the (+) and (-) strands differ by less than 2-fold when they are replicated either as the leading or lagging strand. This is in contrast to the 33- and 8-fold differences observed earlier for G(.)dTTP and C(.)dTTP mispairs on the (+) strand when replicated by the leading or lagging strand complex (Roberts, J. D., Izuta, S., Thomas, D. C., and Kunkel, T. A. (1994) J. Biol. Chem. 269, 1711-1717), Thus, the relative fidelity of the leading and lagging strand replication proteins varies with the mispair and sequence considered, Misincorporation of dGTP preferentially occurs at template positions where dGTP is the next correct nucleotide to be incorporated, This ''next nucleo tide'' effect is characteristic of reduced exonucleolytic proofreading and suggests that these replication errors are normally proofread efficiently, Fidelity measure ments performed in the absence or presence of dGMP, an inhibitor of proofreading exonuclease activity, suggest that the leading strand replication complex proofreads some mispairs more efficiently than does the lagging strand replication complex. C1 NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. NR 29 TC 27 Z9 28 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 FEB 10 PY 1995 VL 270 IS 6 BP 2595 EP 2600 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QF535 UT WOS:A1995QF53500031 PM 7852323 ER PT J AU BLAKESLEY, VA KATO, H ROBERTS, CT LEROITH, D AF BLAKESLEY, VA KATO, H ROBERTS, CT LEROITH, D TI MUTATION OF A CONSERVED AMINO-ACID RESIDUE (TRYPTOPHAN-1173) IN THE TYROSINE KINASE DOMAIN OF THE IGF-I RECEPTOR ABOLISHES AUTOPHOSPHORYLATION BUT DOES NOT ELIMINATE BIOLOGIC FUNCTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN INSULIN-RECEPTOR; SIGNAL TRANSDUCTION; GROWTH; REPLACEMENT; FAMILY; HORMONE; MUTANT; SITES AB The amino acid sequence of the tyrosine kinase domain of the insulin-like growth factor-I (IGF-I) receptor is 84% identical to the sequence of the analogous region of the insulin receptor, A naturally occurring mutation of the tryptophan residue at position 1200 of the insulin receptor to serine results in impaired beta subunit autophosphorylation of wheat germ agglutinin-purified receptors, severely impaired thymidine incorporation and moderately reduced glycogen synthesis; however, glucose uptake was unaffected. To study the importance of this residue in IGF-I receptor function, we mutated the analogous tryptophan residue at position 1173 of the IGF-I receptor to serine and overexpressed the mutant receptor in NIH-3T3 cells, In cell Lines overexpressing this mutant IGF-I receptor, beta subunit autophosphorylation was severely reduced. Additionally, the overexpressed mutant receptors exhibited a dominant-negative effect on IGF-I-stimulated autophosphorylation of endogenous mouse IGF-I receptors, Phosphorylation of insulin receptor substrate (IRS)-1 in intact cells by the mutant IGF-I receptors was similar to the level of IRS-1 phosphorylation seen in the parental NIH-3T3 cells, but there was no obvious dominant-negative effect on IRS-1 phosphorylation. Wheat germ agglutinin-purified mutant receptors were as active in phosphorylating poly(Glu,Tyr) 4:1 as wild-type IGF-I receptors, suggesting that, in intact cells, additional factors are necessary in order for the IGF-I receptor to phosphorylate IRS-1, Thymidine incorporation was severely reduced in one clone overexpressing the mutant IGF-I receptor and abolished in a second clone, Glucose uptake in both clones was reduced to about half of that seen in a cell line overexpressing mild-type IGF-I receptors. Thus, we propose that the tryptophan residue at position 1173 of the IGF-I receptor is important in the regulation of autophosphorylation in vivo. This study again confirms that high levels of autophosphorylation are not required for mediation of all of the biologic activities of the IGF-I receptor. C1 NIDDK,DIABET BRANCH,BETHESDA,MD 20892. OI Roberts, Charles/0000-0003-1756-5772 NR 30 TC 32 Z9 32 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 FEB 10 PY 1995 VL 270 IS 6 BP 2764 EP 2769 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QF535 UT WOS:A1995QF53500057 PM 7852347 ER PT J AU JACOBSON, KA FISCHER, B VANRHEE, AM AF JACOBSON, KA FISCHER, B VANRHEE, AM TI MOLECULAR PROBES FOR MUSCARINIC RECEPTORS - FUNCTIONALIZED CONGENERS OF SELECTIVE MUSCARINIC ANTAGONISTS SO LIFE SCIENCES LA English DT Article; Proceedings Paper CT 6th International Symposium on Subtypes of Muscarinic Receptors CY NOV 09-12, 1994 CL FT LAUDERDALE, FL SP BOSTON UNIV SCH MED, JOHANN WOLFGANG GOETHE UNIV DE TELENZEPINE; MOLECULAR MODELING; FLUORESCENCE; G-PROTEIN COUPLED RECEPTORS ID BINDING; IDENTIFICATION; PIRENZEPINE; TELENZEPINE; DERIVATIVES; AGENTS; DESIGN AB The muscarinic agonist oxotremorine and the tricyclic muscarinic antagonists pirenzepine and telenzepine have been derivatized using a functionalized congener approach for the purpose of synthesizing high affinity ligand probes that are suitable for conjugation with prosthetic groups, for receptor cross-linking, fluorescent and radioactive detection, etc. A novel fluorescent conjugate of TAC (telenzepine amine congener), an n-decylamino derivative of the mi-selective antagonist, with the fluorescent trisulfonated pyrene dye Cascade Blue may be useful for assaying the receptor as an alternative to radiotracers. In a rat m3 receptor mutant containing a single amino acid substitution in the sixth transmembrane domain (Asn507 to Ala) the parent telenzepine lost 636-fold in affinity, while TAC lost only 27-fold. Thus, the decylamino group of TAC stabilizes the bound state and thus enhances potency by acting as a distal anchor in the receptor binding site. We have built a computer-assisted molecular model of the transmembrane regions of muscarinic receptors based on homology with the G-protein coupled receptor rhodopsin, for which a low resolution structure is known. We have coordinated the antagonist pharmacophore (tricyclic and piperazine moieties) with residues of the third and seventh helices of the rat m3 receptor. Although the decylamino chain of TAC is likely to be highly flexible and may adopt many conformations, we located one possible site for a salt bridge formation with the positively charged -NH3+ group, i.e. Asp113 in helix II. RP JACOBSON, KA (reprint author), NIDDK,BIOORGAN CHEM LAB,MOLEC RECOGNIT SECT,BETHESDA,MD 20892, USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031115-24]; NIMH NIH HHS [N01MH30003] NR 30 TC 10 Z9 10 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD FEB 10 PY 1995 VL 56 IS 11-12 BP 823 EP 830 DI 10.1016/0024-3205(95)00016-Y PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA QG909 UT WOS:A1995QG90900004 PM 10188781 ER PT J AU WESS, J BLIN, N MUTSCHLER, E BLUML, K AF WESS, J BLIN, N MUTSCHLER, E BLUML, K TI MUSCARINIC ACETYLCHOLINE-RECEPTORS - STRUCTURAL BASIS OF LIGAND-BINDING AND G-PROTEIN COUPLING SO LIFE SCIENCES LA English DT Article; Proceedings Paper CT 6th International Symposium on Subtypes of Muscarinic Receptors CY NOV 09-12, 1994 CL FT LAUDERDALE, FL SP BOSTON UNIV SCH MED, JOHANN WOLFGANG GOETHE UNIV DE SITE-DIRECTED MUTAGENESIS; LIGAND BINDING SITE; RECEPTOR G PROTEIN COUPLING; G PROTEIN COUPLING ID SITE-DIRECTED MUTAGENESIS; BETA-ADRENERGIC-RECEPTOR; MUTATIONAL ANALYSIS; TYROSINE RESIDUES; AMINO-ACIDS; M3-MUSCARINIC-RECEPTOR; IDENTIFICATION; ACTIVATION; SPECIFICITY; THREONINE AB Muscarinic acetylcholine receptors (m1-m5) were studied by a combined molecular genetic/pharmacologic approach to elucidate the molecular characteristics of the ligand binding site and of the receptor domains involved in G protein coupling. Site-directed mutagenesis studies of the rat m3 muscarinic receptor suggest that the acetylcholine binding domain is formed by a series of hydrophilic amino acids located in the ''upper'' half of transmembrane domains (TM) III, V, VI, and VII. Moreover, we showed that mutational modification of a TM VI Asn residue (Asn507 in the rat m3 receptor sequence) which is characteristic for the muscarinic receptor family has little effect on high-affinity acetylcholine binding and receptor activation, but results in dramatic reductions in binding affinities for certain subclasses of muscarinic antagonists. The N-terminal portion of the third intracellular loop (i3) of muscarinic and other G protein-coupled receptors has been shown to play a central role in determining the G protein coupling profile of a given receptor subtype. Insertion mutagenesis studies with the rat m3 muscarinic receptor suggest that this region forms an amphiphilic alpha-helix and that the hydrophobic side of this helix represents an important G protein recognition surface. Further mutational analysis of this receptor segment showed that Tyr254 located at the N-terminus of the i3 loop of the m3 muscarinic receptor plays a key role in muscarinic receptor-induced Gq activation. The studies described here, complemented by biochemical and biophysical approaches, should eventually lead to a detailed structural model of the ligand-receptor-G protein complex. C1 UNIV FRANKFURT,BIOCTR NIEDERURSEL,DEPT PHARMACOL,D-60053 FRANKFURT,GERMANY. RP WESS, J (reprint author), NIDDKD,BIOORGAN CHEM LAB,BLDG 8A,ROOM B1A-09,BETHESDA,MD 20892, USA. NR 35 TC 57 Z9 58 U1 4 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD FEB 10 PY 1995 VL 56 IS 11-12 BP 915 EP 922 DI 10.1016/0024-3205(95)00028-5 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA QG909 UT WOS:A1995QG90900016 PM 10188793 ER PT J AU ECKELMAN, WC KIESEWETTER, DO LANG, L LEE, JT PARK, SG PAIK, CH AF ECKELMAN, WC KIESEWETTER, DO LANG, L LEE, JT PARK, SG PAIK, CH TI SUBTYPE-SELECTIVE MUSCARINIC LIGANDS FOR RECEPTOR IMAGING SO LIFE SCIENCES LA English DT Meeting Abstract C1 NIH,CTR CLIN,DEPT POSITRON EMISS TOMOG,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT NUCL MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD FEB 10 PY 1995 VL 56 IS 11-12 BP 1018 EP 1018 DI 10.1016/0024-3205(95)93748-4 PG 1 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA QG909 UT WOS:A1995QG90900058 ER PT J AU BLIN, N WESS, J AF BLIN, N WESS, J TI MAPPING OF MUSCARINIC RECEPTOR DOMAINS CONFERRING SPECIFICITY OF COUPLING TO GQ SO LIFE SCIENCES LA English DT Meeting Abstract C1 NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD FEB 10 PY 1995 VL 56 IS 11-12 BP 1032 EP 1032 DI 10.1016/0024-3205(95)93776-B PG 1 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA QG909 UT WOS:A1995QG90900085 ER PT J AU YARMOLINSKY, MB AF YARMOLINSKY, MB TI PROGRAMMED CELL-DEATH IN BACTERIAL-POPULATIONS SO SCIENCE LA English DT Editorial Material ID ESCHERICHIA-COLI; STABLE MAINTENANCE; SELFISH GENES; PLASMID R100; F-PLASMID; PROTEIN; GROWTH; SYSTEM; CCD; PEM RP YARMOLINSKY, MB (reprint author), NCI,BIOCHEM LAB,BLDG 37,ROOM 4D-15,BETHESDA,MD 20892, USA. NR 38 TC 246 Z9 257 U1 3 U2 14 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD FEB 10 PY 1995 VL 267 IS 5199 BP 836 EP 837 DI 10.1126/science.7846528 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QG207 UT WOS:A1995QG20700044 PM 7846528 ER PT J AU MIYAMOTO, S AKIYAMA, SK YAMADA, KM AF MIYAMOTO, S AKIYAMA, SK YAMADA, KM TI SYNERGISTIC ROLES FOR RECEPTOR OCCUPANCY AND AGGREGATION IN INTEGRIN TRANSMEMBRANE FUNCTION SO SCIENCE LA English DT Article ID FIBRONECTIN RECEPTOR; SIGNAL TRANSDUCTION; CELL-ADHESION; TYROSINE PHOSPHORYLATION; FIBROBLASTS; ANTIBODIES; BINDING; PROTEIN; MATRIX; GROWTH AB Integrin receptors mediate cell adhesion, signal transduction, and cytoskeletal organization. How a single transmembrane receptor can fulfill multiple functions was clarified by comparing roles of receptor occupancy and aggregation. Integrin occupancy by monovalent ligand induced receptor redistribution, but minimal tyrosine phosphorylation signaling or cytoskeletal protein redistribution. Aggregation of integrins by noninhibitory monoclonal antibodies on beads induced intracellular accumulations of pp125(FAK) and tensin, as well as phosphorylation, but no accumulation of other cytoskeletal proteins such as talin. Combining antibody-mediated clustering with monovalent ligand occupancy induced accumulation of seven cytoskeletal proteins, including alpha-actinin, talin, and F-actin, thereby mimicking multivalent interactions with fibronectin or polyvalent peptides. Integrins therefore mediate a complex repertoire of functions through the distinct effects of receptor aggregation, receptor occupancy, or both together. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. OI Yamada, Kenneth/0000-0003-1512-6805 NR 28 TC 758 Z9 761 U1 0 U2 24 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD FEB 10 PY 1995 VL 267 IS 5199 BP 883 EP 885 DI 10.1126/science.7846531 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QG207 UT WOS:A1995QG20700058 PM 7846531 ER PT J AU BIRD, GS BIAN, XP PUTNEY, JW AF BIRD, GS BIAN, XP PUTNEY, JW TI CALCIUM-ENTRY SIGNAL SO NATURE LA English DT Letter ID INFLUX; CELLS RP BIRD, GS (reprint author), NIEHS,CELLULAR & MOLEC PHARMACOL LAB,CALCIUM REGULAT SECT,RES TRIANGLE PK,NC 27709, USA. NR 7 TC 36 Z9 36 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD FEB 9 PY 1995 VL 373 IS 6514 BP 481 EP 482 DI 10.1038/373481b0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QF724 UT WOS:A1995QF72400042 PM 7845458 ER PT J AU GAMES, D ADAMS, D ALESSANDRINI, R BARBOUR, R BERTHELETTE, P BLACKWELL, C CARR, T CLEMENS, J DONALDSON, T GILLESPIE, F GUIDO, T HAGOPIAN, S JOHNSONWOOD, K KHAN, K LEE, M LEIBOWITZ, P LIEBERBURG, I LITTLE, S MASLIAH, E MCCONLOGUE, L MONTOYAZAVALA, M MUCKE, L PAGANINI, L PENNIMAN, E POWER, M SCHENK, D SEUBERT, P SNYDER, B SORIANO, F TAN, H VITALE, J WADSWORTH, S WOLOZIN, B ZHAO, J AF GAMES, D ADAMS, D ALESSANDRINI, R BARBOUR, R BERTHELETTE, P BLACKWELL, C CARR, T CLEMENS, J DONALDSON, T GILLESPIE, F GUIDO, T HAGOPIAN, S JOHNSONWOOD, K KHAN, K LEE, M LEIBOWITZ, P LIEBERBURG, I LITTLE, S MASLIAH, E MCCONLOGUE, L MONTOYAZAVALA, M MUCKE, L PAGANINI, L PENNIMAN, E POWER, M SCHENK, D SEUBERT, P SNYDER, B SORIANO, F TAN, H VITALE, J WADSWORTH, S WOLOZIN, B ZHAO, J TI ALZHEIMER-TYPE NEUROPATHOLOGY IN TRANSGENIC MICE OVEREXPRESSING V717F BETA-AMYLOID PRECURSOR PROTEIN SO NATURE LA English DT Article ID SENILE PLAQUES; DISEASE; IDENTIFICATION; EXPRESSION; PATHOLOGY; DEPOSITS; PEPTIDE; CHAIN; BRAIN; GENE AB ALZHEIMER'S disease (AD) is the most common cause of progressive intellectual failure in aged humans. AD brains contain numerous amyloid plaques surrounded by dystrophic neurites, and show profound synaptic loss, neurofibrillary tangle formation and gliosis. The amyloid plaques are composed of amyloid beta-peptide (A beta), a 40-42-amino-acid fragment of the beta-amyloid precursor protein (APP)(1). A primary pathogenic role for APP/A beta is suggested by missense mutations in APP that are tightly linked to autosomal dominant forms of AD(2,3). A major obstacle to elucidating and treating AD has been the lack of an animal model. Animals transgenic for APP have previously failed to show extensive AD-type neuropathology(4-10), but we now report the production of transgenic mice that express high levels of human mutant APP (with valine at residue 717 substituted by phenylalanine) and which progressively develop many of the pathological hallmarks of AD, including numerous extracellular thioflavin S-positive AP deposits, neuritic plaques, synaptic loss, astrocytosis and microgliosis. These mice support a primary role for APP/A beta in the genesis of AD and could provide a preclinical model for testing therapeutic drugs. C1 ATHENA NEUROSCI INC, S SAN FRANCISCO, CA 94080 USA. EXEMPLAR CORP, WORCESTER, MA 01605 USA. ELI LILLY & CO, LILLY RES LAB, INDIANAPOLIS, IN 46285 USA. SCRIPPS RES INST, RES INST, DEPT NEUROPHARMACOL, LA JOLLA, CA 92037 USA. UNIV CALIF SAN DIEGO, DEPT NEUROSCI, LA JOLLA, CA 92093 USA. NIMH, CLIN SCI LAB, BETHESDA, MD 20892 USA. NR 29 TC 1879 Z9 1914 U1 6 U2 126 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD FEB 9 PY 1995 VL 373 IS 6514 BP 523 EP 527 DI 10.1038/373523a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QF724 UT WOS:A1995QF72400060 PM 7845465 ER PT J AU SIDELL, N WADA, R HAN, GY CHANG, BS SHACK, S MOORE, T SAMID, D AF SIDELL, N WADA, R HAN, GY CHANG, BS SHACK, S MOORE, T SAMID, D TI PHENYLACETATE SYNERGIZES WITH RETINOIC ACID IN INDUCING THE DIFFERENTIATION OF HUMAN NEUROBLASTOMA-CELLS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID HUMAN NEURO-BLASTOMA; ACETYLCHOLINESTERASE ACTIVITY; EXPRESSION; CARCINOMA; IDENTIFICATION; RECEPTORS; CHILDREN; LINES AB Phenylacetate, a natural metabolite of phenylalanine which was originally described as a plant growth hormone, has recently gained attention as a possible differentiation inducer for a variety of human tumor cell types. This interest prompted us to assess the ability of sodium phenylacetate (NaPA) to promote the differentiation of human neuroblastoma cells, both alone and in combination with retinoic acid (RA), a known inducer of neuroblastoma differentiation and maturation. Using the LA-N-5 cell line, we have determined that NaPA can stimulate the differentiation of neuroblastoma cells, as evidenced by dose-dependent inhibition of cell proliferation, neurite outgrowth, increased acetylcholinesterase activity and reduction of N-myc expression. Furthermore, NaPA and RA synergized in inducing differentiation, in that combination treatment resulted in cessation of cell growth along with morphologic and biochemical changes indicative of the loss of malignant properties. We have determined that NaPA can markedly enhance mRNA levels of the nuclear RA receptor-beta (RAR beta) in LA-N-5 cells prior to morphologic or other phenotypic changes induced by this compound. This effect appeared to be distinct from the ability of NaPA to alter tumor cell lipid metabolism via inhibition of protein isoprenylation. Thus among its varied effects on LA-N-5 cells, NaPA appears to interact with the RA pathway at the nuclear level by up-regulating RAR beta expression. (C) 1995 Wiley-Liss, Inc. C1 UNIV CALIF LOS ANGELES,SCH MED,BRAIN RES INST,DEPT PATHOL & LAB MED NEUROPATHOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,JONSSON COMPREHENS CANC CTR,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PEDIAT,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,GWYNNE HAZEN CHERRY MEM LABS,LOS ANGELES,CA 90024. NCI,DIV CANC TREATMENT,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [CA30515, CA43503]; NINDS NIH HHS [NS32128] NR 28 TC 44 Z9 50 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 FEB 8 PY 1995 VL 60 IS 4 BP 507 EP 514 DI 10.1002/ijc.2910600414 PG 8 WC Oncology SC Oncology GA QG237 UT WOS:A1995QG23700013 PM 7829265 ER PT J AU HYDE, TM WEINBERGER, DR AF HYDE, TM WEINBERGER, DR TI TOURETTES-SYNDROME - A MODEL NEUROPSYCHIATRIC DISORDER SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Discussion ID BASAL GANGLIA; DELATOURETTES,GILLES SYNDROME; MONOZYGOTIC TWINS; CHILDREN C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,CLIN BRAIN DISORDERS BRANCH,INTRAMURAL RES PROGRA,WASHINGTON,DC 20032. NR 33 TC 31 Z9 32 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 8 PY 1995 VL 273 IS 6 BP 498 EP 501 DI 10.1001/jama.273.6.498 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA QE498 UT WOS:A1995QE49800035 PM 7530781 ER PT J AU LUBAS, WA SMITH, M STARR, CM HANOVER, JA AF LUBAS, WA SMITH, M STARR, CM HANOVER, JA TI ANALYSIS OF NUCLEAR-PORE PROTEIN P62 GLYCOSYLATION SO BIOCHEMISTRY LA English DT Article ID LINKED N-ACETYLGLUCOSAMINE; CYTOPLASMIC PROTEINS; O-GLCNAC; COMPLEX GLYCOPROTEINS; TRANSCRIPTION FACTOR; SERINE-RICH; CONTAINS; DOMAIN; LOCALIZATION; POLYPEPTIDE AB Glycoprotein components of the nuclear pore are essential for nuclear transport and are modified by both glycosylation and phosphorylation. The function and control of these post-translational modifications are poorly understood. Glycosylation of the major rat nuclear pore glycoprotein, p62, was examined in vitro using recombinant p62 as a substrate. Rat p62 was expressed in Escherichia coli and purified to near homogeneity. Kinetic analysis using a partially purified mammalian transferase suggests that the recombinant protein is an excellent substrate (K-m = 0.30 mu M) for the transfer of GlcNAc from UDP-GlcNAc (K-m = 1.8 mu M). Localization of the sites of O-linked GlcNAc glycosylation of rat p62 was performed by a combination of deletion analysis of in vitro translation products and by immunoprecipitation of [C-14]GlcNAc-labeled proteolytic fragments. The amino terminus of rat p62 is poorly glycosylated with no O-linked GlcNAc sites between Lys(22) and Lys(97); the carboxyl terminus has one known glycosylation site at Ser(471). The majority of the glycosylation sites in rat p62 are likely to occur on the six clustered Ser residues in the central Ser/Thr-rich region from Ser(270) to Thr(294). A synthetic peptide derived from this region is a good substrate for O-GlcNAc addition (K-m = 30 mu M) and a potent competitive inhibitor of p62 glycosylation (K-i = 15 mu M). It is proposed that this Ser/Thr-rich domain functions as a linker region between the amino-terminal beta-pleated sheet and the carboxyl terminal alpha-helical domains. O-Glycosylation and phosphorylation of this linker region could provide a dynamic means of altering the conformation of p62 during nuclear pore assembly and disassembly. C1 NIDDK,LCBB,BIOCHEM & METAB LAB,BETHESDA,MD 20892. NR 49 TC 52 Z9 53 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 7 PY 1995 VL 34 IS 5 BP 1686 EP 1694 DI 10.1021/bi00005a025 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QF837 UT WOS:A1995QF83700025 PM 7849028 ER PT J AU OTAKA, A MIYOSHI, K ROLLER, PP BURKE, TR TAMAMURA, H FUJII, N AF OTAKA, A MIYOSHI, K ROLLER, PP BURKE, TR TAMAMURA, H FUJII, N TI PRACTICAL SYNTHESIS OF PHOSPHOPEPTIDES USING DIMETHYL-PROTECTED PHOSPHOAMINO ACID-DERIVATIVES SO JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS LA English DT Article ID DEPROTECTION AB A practical synthesis of phosphopeptides was achieved using a combination of dimethyl-protected phosphoamino acids and two-step deprotection protocols consisting of high acidic (S(N)1/S(N)2) and low acidic (S(N)2) reagent systems. C1 NCI,MED CHEM LAB,BETHESDA,MD 20892. RP OTAKA, A (reprint author), KYOTO UNIV,FAC PHARMACEUT SCI,SAKYO KU,KYOTO 606,JAPAN. RI Burke, Terrence/N-2601-2014 NR 13 TC 9 Z9 9 U1 0 U2 0 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE SCIENCE PARK MILTON ROAD, CAMBRIDGE, CAMBS, ENGLAND CB4 4WF SN 0022-4936 J9 J CHEM SOC CHEM COMM JI J. Chem. Soc.-Chem. Commun. PD FEB 7 PY 1995 IS 3 BP 387 EP 389 DI 10.1039/c39950000387 PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA QG935 UT WOS:A1995QG93500046 ER PT J AU AKSAMIT, RR BUGGY, JJ BAUER, CE AF AKSAMIT, RR BUGGY, JJ BAUER, CE TI EXPRESSION OF RAT-LIVER ADOHCY HYDROLASE IN A RHODOBACTER-CAPSULATUS AHCY MUTANT RESTORES PIGMENT FORMATION AND PHOTOSYNTHETIC GROWTH SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID S-ADENOSYLHOMOCYSTEINE HYDROLASE; L-HOMOCYSTEINE HYDROLASE; AMINO-ACID SEQUENCE; REACTION-MECHANISM; CDNA SEQUENCE; REGION; GENE; PURIFICATION; MUTAGENESIS; TOBACCO AB An amino acid alignment of fourteen S-adenosylhomocysteine hydrolases shows that sequences from six photosynthetic species and one species possibly derived from algae have an internal 36 to 41 amino acid sequence that is not present in hydrolase sequences from seven nonphotosynthetic species. In the photosynthetic eubacterium Rhodobacter capsulatus, the StLB1 strain has a disrupted hydrolase gene, and hydrolase activity is not detectable. Photopigment synthesis and photosynthetic growth are significantly reduced in the StLB1 strain. Introduction of rat hydrolase cDNA into the StLB1 strain restored hydrolase activity, photopigment synthesis and photosynthetic growth. The results show that the 36 amino acid sequence of Rhodobacter capsulatus S-adenosylhomocysteine hydrolase does not have a photosynthesis specific function. (C) 1995 Academic Press, Inc.. C1 INDIANA UNIV,DEPT BIOL,BLOOMINGTON,IN 47405. RP AKSAMIT, RR (reprint author), NIMH,GEN & COMPARAT BIOCHEM LAB,BLDG 36 RM 3D06,36 CONVENT DR,MSC 4094,BETHESDA,MD 20892, USA. FU NIGMS NIH HHS [GM00618, GM 40941, R01 GM040941] NR 28 TC 1 Z9 1 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD FEB 6 PY 1995 VL 207 IS 1 BP 265 EP 272 DI 10.1006/bbrc.1995.1182 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QF833 UT WOS:A1995QF83300039 PM 7857275 ER PT J AU MORELLI, A FALCHETTI, A WEINSTEIN, L FABIANI, S TOMASSETTI, P ENZI, G CARRARO, R BORDI, C TONELLI, F BRANDI, ML AF MORELLI, A FALCHETTI, A WEINSTEIN, L FABIANI, S TOMASSETTI, P ENZI, G CARRARO, R BORDI, C TONELLI, F BRANDI, ML TI RFLP ANALYSIS OF HUMAN-CHROMOSOME-11 REGION-Q13 IN MULTIPLE SYMMETRICAL LIPOMATOSIS AND MULTIPLE ENDOCRINE NEOPLASIA TYPE-1-ASSOCIATED LIPOMAS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PARATHYROID TUMORS; ADIPOSE-TISSUE; LOCALIZATION; FEATURES; ALLELES; DEFECT; 11Q13; DNA AB Six lipomas from patients affected by Multiple Symmetric Lipomatosis (MSL) and by Multiple Endocrine Neoplasia Type 1 (MEN 1) were analyzed for loss of heterozygosity on chromosome 11 region q12-13 using four RFLPs. Allelic loss for the D11S146 locus was found only in one visceral MEN 1-associated lipoma. Lipomas that exhibited a lack of allelic lesions were analyzed for an eventual abnormal amount or a defective function of the Gs protein by studying the Gsa subunit gene, codons 201 and 207, by PCR and TGGE techniques. All the samples were negative for activating mutations. (C) 1995 Academic Inc. Press, Inc. C1 UNIV FLORENCE,DEPT CLIN PHYSIOPATHOL,ENDOCRINE UNIT,I-50139 FLORENCE,ITALY. UNIV FLORENCE,DEPT CLIN PHYSIOPATHOL,SURG PATHOL UNIT,I-50139 FLORENCE,ITALY. NIDDK,MOLEC PATHOPHYSIOL BRANCH,BETHESDA,MD. UNIV BOLOGNA,INST CLIN MED & GASTROENTEROL,I-40126 BOLOGNA,ITALY. UNIV PADUA,DEPT INTERNAL MED,I-35100 PADUA,ITALY. UNIV PARMA,INST PATHOL,I-43100 PARMA,ITALY. RI FALCHETTI, ALBERTO/Q-1787-2016 OI FALCHETTI, ALBERTO/0000-0002-6739-4417 NR 26 TC 25 Z9 26 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD FEB 6 PY 1995 VL 207 IS 1 BP 363 EP 368 DI 10.1006/bbrc.1995.1196 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QF833 UT WOS:A1995QF83300053 PM 7531972 ER PT J AU JOSEPH, JA CAO, G CUTLER, RC AF JOSEPH, JA CAO, G CUTLER, RC TI IN-VIVO OR IN-VITRO ADMINISTRATION OF THE NITRONE SPIN-TRAPPING COMPOUND, N-TERT-BUTYL-ALPHA-PHENYLNITRONE, (PBN) REDUCES AGE-RELATED DEFICITS IN STRIATAL MUSCARINIC RECEPTOR SENSITIVITY SO BRAIN RESEARCH LA English DT Article DE OXIDATIVE STRESS; AGING; MUSCARINIC RECEPTOR; STRIATUM ID HEAVY-PARTICLE IRRADIATION; PROTECTIVE ACTIVITY; RAT-HEART; CARDIOTOXICITY; DOPAMINE; MODULATION; SENESCENCE; ADRIAMYCIN; OXIDATION; RADIATION AB Previous research has indicated that age-related reductions in muscarinic (m) (e.g. oxotremorine, Ore) agonist enhancement of striatal K+-evoked dopamine release (K+-ERDA) and decreased IP3 release upon m receptor (mAChR) agonist stimulation are partially the result of deficits in signal transduction (ST). The present experiments were carried out to test the hypothesis that these age-related ST deficits occur as a result of free radical-induced alterations in membranes containing receptor-G protein complexes. To test this hypothesis, the effects of in vivo and in vitro administration of the nitrone trapping agent, n-tert-butyl-alpha-phenylnitrone (PEN), on the Ore-enhancement of K+-ERDA were examined. Results showed that: both in vivo (10 mg/kg/2 X day PEN i.p./14 days) in vitro (incubation of striatal slices 0-100 mu M PBN/30 min) applications of PEN were effective in ameliorating age-related deficits in Ore-enhanced K+-ERDA. The results of the in vivo administration of PEN indicate that the loss of mAChR sensitivity in aging may be the result of oxidative stress that can be restored by this nitrone trapping agent. These findings show that reductions of endogenous or exogenous free radicals may alter one important biomarker of aging, i.e. the loss of sensitivity in mAChR systems. However, these results, when considered along with those obtained with in vitro administration indicate that in addition, PEN may have acute effects (e.g. perhaps membrane structural alterations) which can also improve mAChR responsiveness. C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RP JOSEPH, JA (reprint author), USDA ARS,HUMAN NUTR RES CTR AGING,711 WASHINGTON ST,BOSTON,MA 02111, USA. NR 32 TC 27 Z9 27 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD FEB 6 PY 1995 VL 671 IS 1 BP 73 EP 77 DI 10.1016/0006-8993(94)01320-H PG 5 WC Neurosciences SC Neurosciences & Neurology GA QG261 UT WOS:A1995QG26100009 PM 7728535 ER PT J AU HASHIMOTO, K LONDON, ED AF HASHIMOTO, K LONDON, ED TI INTERACTIONS OF ERYTHRO-IFENPRODIL, THREO-IFENPRODIL, ERYTHRO-IODOIFENPRODIL, AND ELIPRODIL WITH SUBTYPES OF SIGMA-RECEPTORS SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Note DE SIGMA RECEPTOR; IFENPRODIL; ELIPRODIL; SUBTYPE; RECEPTOR BINDING; BRAIN, RAT ID POLYAMINE-SENSITIVE SITE; H-3 IFENPRODIL; BINDING-SITES; RAT-BRAIN; ANTAGONIST AB Observations of sigma (sigma) receptor heterogeneity have prompted interest in identifying ligands for sigma receptor subtypes. Selective ligands for the sigma-2 are unavailable, but [H-3]ifenprodil labels sigma-2 sites. Therefore, isomers and analogues of ifenprodil were compared as potential sigma-2 ligands. Threo-ifenprodil and erythro-ifenprodil had high affinity (K-i similar or equal to 2 nM) for sigma-2 sites; erythro-iodoifenprodil had moderate affinity (K-i similar or equal to 46 nM); eliprodil had lowest affinity (K-i similar or equal to 630 nM). Threo-ifenprodil, which has less affinity for alpha(1)-adrenoceptors than erythro-ifenprodil, was slightly more selective than erythro-ifenprodil for sigma-2 sites. These results identify threo-ifenprodil as potentially useful for studies of sigma-2 receptors. C1 NIDA,INTRAMURAL RES PROGRAM,NEUROSCI BRANCH,NEUROIMAGING & DRUG ACT SECT,BALTIMORE,MD 21224. JOHNS HOPKINS MED INST,DEPT RADIOL,BALTIMORE,MD 21205. UNIV MARYLAND,SCH MED,DEPT PHARMACOL & EXPTL THERAPEUT,BALTIMORE,MD 21201. NR 14 TC 32 Z9 33 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 FEB 6 PY 1995 VL 273 IS 3 BP 307 EP 310 DI 10.1016/0014-2999(94)00763-W PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QG363 UT WOS:A1995QG36300018 PM 7737340 ER PT J AU BYCHKOVA, VE PTITSYN, OB AF BYCHKOVA, VE PTITSYN, OB TI FOLDING INTERMEDIATES ARE INVOLVED IN GENETIC-DISEASES SO FEBS LETTERS LA English DT Article DE PROTEIN FOLDING; GENETIC DISEASE; MOLTEN GLOBULE STATE; MISLOCATION OF PROTEINS ID TRANSMEMBRANE CONDUCTANCE REGULATOR; TAIL SPIKE PROTEIN; INTRACELLULAR-TRANSPORT; SUBUNIT; MUTATIONS; SURFACE AB Recent experimental data show that some human genetic diseases are due to mutations in proteins which influence their trafficking and lead to retaining of proteins in the endoplasmic reticulum or their unproper processing. In this paper a hypothesis is proposed that these mutations are connected with an incomplete protein folding, blocking it at the stage of the kinetic molten globule or even earlier. If so, the specific drugs against these diseases may be ligands and other factors which facilitate the correct protein folding. C1 NCI,MATH BIOL LAB,BETHESDA,MD 20892. RP BYCHKOVA, VE (reprint author), RUSSIAN ACAD SCI,INST PROT RES,PUSHCHINO 142292,RUSSIA. NR 35 TC 56 Z9 56 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD FEB 6 PY 1995 VL 359 IS 1 BP 6 EP 8 DI 10.1016/0014-5793(95)00004-S PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA QG380 UT WOS:A1995QG38000002 PM 7531653 ER PT J AU WEBSTER, MJ BACHEVALIER, J UNGERLEIDER, LG AF WEBSTER, MJ BACHEVALIER, J UNGERLEIDER, LG TI TRANSIENT SUBCORTICAL CONNECTIONS OF INFERIOR TEMPORAL AREAS TE AND TEO IN INFANT MACAQUE MONKEYS SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Review DE VISUAL CORTEX; DEVELOPMENT; SUPERIOR COLLICULUS; CAUDATE; NUCLEUS MEDIALIS DORSALIS ID CALLOSAL PROJECTION NEURONS; OCULAR DOMINANCE COLUMNS; FETAL RHESUS-MONKEY; MEDIAL THALAMIC LESIONS; CATS VISUAL-CORTEX; POSTNATAL-DEVELOPMENT; CORTICAL PROJECTIONS; CORPUS-CALLOSUM; COLLATERAL ELIMINATION; MACACA-FASCICULARIS AB As part of a long-term study designed to examine the ontogeny of visual memory in monkeys and its underlying neural circuitry, we have examined the subcortical connections of the inferior temporal cortex in infant monkeys and compared them to those previously described in adult monkeys (Webster et al. [1993] J. Comp. Neurol. 335:73-91). Inferior temporal areas TEO and TE were injected with wheat germ agglutinin conjugated to horseradish peroxidase and tritiated amino acids, respectively, or vice versa, in 1-week-old (N = 6) and 3-4-year-old (N = 6) Macaca mulatta, and the distributions of labeled cells and terminals were examined in subcortical structures. Although the connections of inferior temporal cortex with subcortical structures were found to be similar in infant and adult monkeys, several projections appear to undergo refinement during development. Quantitative analysis showed that 1) whereas the projection from TE to the superior colliculus is consistent (5 of 5 cases) and widespread in infants, it is less reliable (2 of 7 cases) and limited in areal extent in adults; 2) although the projections from TE to nucleus medialis dorsalis and the tail of the caudate are present in infants and adults, they are reduced in adults; and 3) TEO receives input from the dorsal lateral geniculate nucleus in both infants and adults, but the number of cells giving rise to this projection is lower in adults. There was also a suggestion that TE projects to nucleus paracentralis in infants (2 of 5 cases) but not in adults (0 of 7 cases). No differences between infants and adults were apparent in other subcortical connections, including those with the pulvinar, reticular nucleus, claustrum, and putamen. (C) 1995 Wileg-Liss, Inc. RP WEBSTER, MJ (reprint author), NIMH,NEUROPSYCHOL LAB,BLDG 49,ROOM 1B80,BETHESDA,MD 20892, USA. NR 130 TC 28 Z9 28 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD FEB 6 PY 1995 VL 352 IS 2 BP 213 EP 226 DI 10.1002/cne.903520205 PG 14 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA QL210 UT WOS:A1995QL21000004 PM 7536756 ER PT J AU HOGAN, BLM AF HOGAN, BLM TI OF BIOETHICS AND EMBRYOS SO SCIENTIST LA English DT Letter RP HOGAN, BLM (reprint author), VANDERBILT UNIV,MED CTR,SCH MED,HHMI,NIH,HUMAN EMBRYO RES PANEL,C-2310 MED CTR N,NASHVILLE,TN 37232, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 SN 0890-3670 J9 SCIENTIST JI Scientist PD FEB 6 PY 1995 VL 9 IS 3 BP 13 EP 13 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA QF084 UT WOS:A1995QF08400011 ER PT J AU TOROK, DS ZIFFER, H AF TOROK, DS ZIFFER, H TI SYNTHESIS AND REACTIONS OF 11-AZAARTEMISININ AND DERIVATIVES SO TETRAHEDRON LETTERS LA English DT Article DE ARTEMISININ; MALARIA; PLASMODIUM FALCIPARUM; DEOXOARTEMISININ ID QINGHAOSU ARTEMISININ; ANTIMALARIAL AB 11-Azaartemisinin was prepared in 454 yield in a one pot, two-step sequence from the reaction of artemisinin with excess ammonia followed by acid treatment Analogous reactions of artemisinin with primary alkylamines gave N-alkylazaartemisinins in similar yields. C1 NIDDK,CHEM PHYS LAB,BETHESDA,MD 20892. NR 14 TC 22 Z9 22 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD FEB 6 PY 1995 VL 36 IS 6 BP 829 EP 832 DI 10.1016/0040-4039(94)02419-C PG 4 WC Chemistry, Organic SC Chemistry GA QF827 UT WOS:A1995QF82700010 ER PT J AU OTAKA, A MIYOSHI, K BURKE, TR ROLLER, PP KUBOTA, H TAMAMURA, H FUJII, N AF OTAKA, A MIYOSHI, K BURKE, TR ROLLER, PP KUBOTA, H TAMAMURA, H FUJII, N TI SYNTHESIS AND APPLICATION OF N-BOC-L-2-AMINO-4-(DIETHYLPHOSPHONO)-4,4-DIFLUOROBUTANOIC ACID FOR SOLID-PHASE SYNTHESIS OF NONHYDROLYZABLE PHOSPHOSERINE PEPTIDE ANALOGS SO TETRAHEDRON LETTERS LA English DT Article ID O-PHOSPHOTYROSINE; DERIVATIVES; PHOSPHONOPEPTIDE; GLU-ABU(P)-LEU; SH2 AB Synthesis of N-Boc-L-2-amino-4-(diethylphosphono)-4,4 acid is reported. This analogue was utilized for the solid-phase synthesis of a peptide containing a nonhydrolyzable phosphoserine mimetic. C1 NCI,DIV CANC TREATMENT,MED CHEM LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. RP OTAKA, A (reprint author), KYOTO UNIV,FAC PHARMACEUT SCI,SAKYO KU,KYOTO 606,JAPAN. RI Burke, Terrence/N-2601-2014 NR 26 TC 51 Z9 51 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD FEB 6 PY 1995 VL 36 IS 6 BP 927 EP 930 DI 10.1016/0040-4039(94)02374-K PG 4 WC Chemistry, Organic SC Chemistry GA QF827 UT WOS:A1995QF82700036 ER PT J AU COOPER, GS AF COOPER, GS TI CHILDBEARING AND RISK OF OVARIAN-CANCER SO LANCET LA English DT Letter ID STATES CASE-CONTROL; COLLABORATIVE ANALYSIS RP COOPER, GS (reprint author), NIEHS,EPIDEMIOL BRANCH A305,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0099-5355 J9 LANCET JI Lancet PD FEB 4 PY 1995 VL 345 IS 8945 BP 317 EP 318 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QE731 UT WOS:A1995QE73100037 PM 7837875 ER PT J AU WOLF, DE MCKINNON, CA DAOU, MC STEPHENS, RM KAPLAN, DR ROSS, AH AF WOLF, DE MCKINNON, CA DAOU, MC STEPHENS, RM KAPLAN, DR ROSS, AH TI INTERACTION WITH TRKA IMMOBILIZES GP75 IN THE HIGH-AFFINITY NERVE GROWTH-FACTOR RECEPTOR COMPLEX SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LATERAL DIFFUSION; NGF RECEPTOR; TRANSLATIONAL DIFFUSION; NEUROTROPHIC FACTOR; LIGAND-BINDING; CHICK-EMBRYO; CELLS; MOBILITY; DIFFERENTIATION; INTERNALIZATION AB It has been proposed that the high affinity nerve growth factor (NGF) receptor required for NGF response is a complex of two receptor proteins, gp75 and the tyrosine kinase TrkA, but direct biochemical or biophysical evidence has been lacking, We have previously shown using fluorescence recovery after photobleaching that gp75 is highly mobile on NGF-nonresponsive cells, but relatively immobile on NGF-responsive cells. In this report, we show that a physical interaction with TrkA causes gp75 immobilization We found that gp75 is relatively mobile on TrkA negative nnr5 cells, a PC12 variant which is nonresponsive to NGF. In contrast, on T14 nnr5 cells (which bear a TrkA expression vector) gp75 is relatively immobile, Similarly, using baculoviruses to express gp75 and TrkA on Sf9 insect cells, we found that TrkA immobilizes gp75 molecules, The related receptor, TrkB, caused a more modest immobilization of gp75. Immobilization was found to require intact TrkA kinase and gp75 cytoplasmic domains, paralleling the requirements of high affinity binding of NGF, Analysis of gp75 diffusion coefficients indicates that mutated gp75 and TrkA molecules may form a complex, even in the absence of the ability to bind NGF with high affinity. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21701. RP WOLF, DE (reprint author), WORCESTER FDN EXPTL BIOL INC,222 MAPLE AVE,SHREWSBURY,MA 01545, USA. FU NINDS NIH HHS [NS21716, NS28760] NR 45 TC 72 Z9 72 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 FEB 3 PY 1995 VL 270 IS 5 BP 2133 EP 2138 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QE493 UT WOS:A1995QE49300025 PM 7836442 ER PT J AU CREMO, CR SELLERS, JR FACEMYER, KC AF CREMO, CR SELLERS, JR FACEMYER, KC TI 2 HEADS ARE REQUIRED FOR PHOSPHORYLATION-DEPENDENT REGULATION OF SMOOTH-MUSCLE MYOSIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LIGHT CHAIN; HEAVY-MEROMYOSIN; ACTIN-FILAMENTS; GIZZARD MYOSIN; MOVEMENT; SUBFRAGMENT-1; CONFORMATION; PROTEOLYSIS; CONTRACTION; FRAGMENTS AB Recent structural evidence (Rayment, I., Holden, H. M., Whittaker, M., Yohn, C. B., Lorenz, M., Holmes, K. C., and Milligan, R. A. (1993) Science 261, 58-65) suggests that the two heads of skeletal muscle myosin interact when the protein is bound to filamentous actin, Direct chemical cross-linking experiments show that the two heads of smooth muscle myosin interact in the presence of filamentous actin and the absence of ATP (Onishi, H., Maita, T., Matsuda, G., and Fujiwara, K. (1992) Biochemistry 31, 1201-1210). Head-head interactions may be important in the mechanism of phosphorylation-dependent regulation of smooth muscle myosin. To explore the structural elements essential for phosphorylation-dependent regulation, we purified a proteolytic fragment of chicken gizzard myosin containing only one head attached to an intact tail. This molecule contained a partially digested regulatory light chain, which was replaced with exogenously added intact light chain in either the thiophosphorylated or the unphosphorylated state, Control experiments showed that this replacement was nearly quantitative and did not alter the actin-activated ATPase of this myosin. Electron micrographs confirmed that the single-headed preparation contained an intact form of single-headed myosin. The unphosphorylated single-headed myosin hydrolyzed ATP rapidly and moved actin filaments in an in vitro motility assay, Phosphorylation had minimal effects upon these properties, Therefore, we conclude that phosphorylation-dependent regulation in this myosin requires two heads. These findings may have important implications in studies of other regulated motor proteins that contain two motor domains. C1 NHLBI,MOLEC CARDIOL LAB,BETHESDA,MD 20892. RP CREMO, CR (reprint author), WASHINGTON STATE UNIV,DEPT BIOCHEM & BIOPHYS,PULLMAN,WA 99164, USA. NR 40 TC 86 Z9 86 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 FEB 3 PY 1995 VL 270 IS 5 BP 2171 EP 2175 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QE493 UT WOS:A1995QE49300031 PM 7836446 ER PT J AU CUSHMAN, M GOLEBIEWSKI, WM POMMIER, Y MAZUMDER, A REYMEN, D DECLERCQ, E GRAHAM, L RICE, WG AF CUSHMAN, M GOLEBIEWSKI, WM POMMIER, Y MAZUMDER, A REYMEN, D DECLERCQ, E GRAHAM, L RICE, WG TI COSALANE ANALOGS WITH ENHANCED POTENCIES AS INHIBITORS OF HIV-1 PROTEASE AND INTEGRASE SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; AURINTRICARBOXYLIC ACID; DNA INTEGRATION; RETROVIRAL INTEGRATION; VIRAL-DNA; INVITRO; PROTEINASE; POLYMERASE; BINDING; ASSAY AB Several new analogues of the novel anti-HIV agent cosalane have been synthesized and evaluated as inhibitors of HIV-1 integrase and protease, HIV-1 replication, HIV-1 and HIV-2 cytopathicity, HIV-1- and HIV-2-mediated syncytium formation, and cytopathicity of a variety of human pathogenic viruses. The congeners displayed enhanced potencies relative to cosalane itself as inhibitors of HIV-1 integrase and protease. The two most potent analogues against HIV-1 integrase displayed IC50 values of 2.2 mu M, while the three most potent compounds against HIV-1 protease had IC50 values in the 0.35-0.39 mu M range. In addition to its activity against HIV-1 and HIV-2 cytopathicity, cosalane inhibited the cytopathic effects of herpes simplex virus-1, herpes simplex virus-2, and human cytomegalovirus at concentrations that were well below the cytotoxic concentrations. Potentially useful antiviral activities were also revealed for some of the new cosalane congeners against influenza virus, Junin virus, and Tacaribe virus. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. KATHOLIEKE UNIV LEUVEN,REGA INST MED RES,B-3000 LOUVAIN,BELGIUM. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,ANTIVIRAL DRUG MECHANISMS LAB,FREDERICK,MD 21702. RP CUSHMAN, M (reprint author), PURDUE UNIV,SCH PHARM & PHARMACAL SCI,DEPT MED CHEM & PHARMACOGNOSY,W LAFAYETTE,IN 47907, USA. FU NCI NIH HHS [N01-CM-17513, N01-CO-74102] NR 63 TC 77 Z9 80 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD FEB 3 PY 1995 VL 38 IS 3 BP 443 EP 452 DI 10.1021/jm00003a007 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA QF319 UT WOS:A1995QF31900007 PM 7853337 ER PT J AU MASCARELLA, SW BAI, X WILLIAMS, W SINE, B BOWEN, WD CARROLL, FI AF MASCARELLA, SW BAI, X WILLIAMS, W SINE, B BOWEN, WD CARROLL, FI TI (+)-CIS-N-(PARA, META, AND ORTHO SUBSTITUTED BENZYL)-N-NORMETAZOCINES - SYNTHESIS AND BINDING-AFFINITY AT THE [H-3] (+)-PENTAZOCINE-LABELED (SIGMA-1)-SITE AND QUANTITATIVE STRUCTURE-AFFINITY RELATIONSHIP STUDIES SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID RECEPTOR LIGANDS; OPIOID RECEPTORS; IMAGING AGENTS; ANALOGS; DRUGS; MODEL AB sigma l receptor ligands have potential pharmacological significance as antipsychotic drugs, as tools in the study of drug-induced motor function disorders, and as radiopharmaceutical imaging agents for the noninvasive imaging of malignant tumors in human subjects. A series of substituted N-benzyl-N-normetazocines were synthesized and their binding affinity at the sigma l receptor evaluated in order to examine the details of the structure-affinity relationships (SAR) of a previously determined high-affinity lead compound, (+)-cis-N-benzyl-N-normetazocine (K-i = 0.67 nM). Variation in the benzyl substituents of these compounds produced a 1590-fold range in affinity at the sigma l receptor from the unsubstituted benzyl analog to the lowest affinity p-tert-butylbenzyl analog (K-i - 1066 nM). The nanomolar binding affinity for the sigma l receptor of (+)-cis-N-(4-fluorobenzyl)-N-normetzocine suggests that this analog may be a useful PET imaging agent. C1 RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NIDDK,MED CHEM LAB,RECEPTOR BIOCHEM & PHARMACOL UNIT,BETHESDA,MD 20892. FU NIDA NIH HHS [DA05721] NR 31 TC 20 Z9 21 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD FEB 3 PY 1995 VL 38 IS 3 BP 565 EP 569 DI 10.1021/jm00003a019 PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA QF319 UT WOS:A1995QF31900019 PM 7853349 ER PT J AU PAUL, WE AF PAUL, WE TI REEXAMINING AIDS RESEARCH PRIORITIES SO SCIENCE LA English DT Editorial Material ID MECHANISM; INFECTION; VACCINE; CELLS; GENE; HIV RP PAUL, WE (reprint author), NIH,OFF AIDS RES,BETHESDA,MD 20892, USA. NR 29 TC 31 Z9 31 U1 0 U2 0 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD FEB 3 PY 1995 VL 267 IS 5198 BP 633 EP 636 DI 10.1126/science.7839138 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QE733 UT WOS:A1995QE73300025 PM 7839138 ER PT J AU LILLY, B ZHAO, B RANGANAYAKULU, G PATERSON, BM SCHULZ, RA OLSON, EN AF LILLY, B ZHAO, B RANGANAYAKULU, G PATERSON, BM SCHULZ, RA OLSON, EN TI REQUIREMENT OF MADS DOMAIN TRANSCRIPTION FACTOR D-MEF2 FOR MUSCLE FORMATION IN DROSOPHILA SO SCIENCE LA English DT Article ID ENHANCER-BINDING-FACTOR; FACTOR MEF-2; GENE; EXPRESSION; PROTEINS; ENCODES; MEMBER; FAMILY; EMBRYOGENESIS; TRANSPOSITION AB Members of the myocyte enhancer binding factor-2 (MEF2) family of MADS (MCM1, agamous, deficiens, and serum response factor) box transcription factors are expressed in the skeletal, cardiac, and smooth muscle lineages of vertebrate and Drosophila embryos. These factors bind an adenine-thymidine-rich DNA sequence associated with muscle-specific genes. The function of MEF2 was determined by generating a loss-of-function of the single mef2 gene in Drosophila (D-mef2). In loss-of-function embryos, somatic, cardiac, and visceral muscle cells did not differentiate, but myoblasts were normally specified and positioned. These results demonstrate that different muscle cell types share a common myogenic differentiation program controlled by MEF2. C1 UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT BIOCHEM & MOLEC BIOL,HOUSTON,TX 77030. NCI,BIOCHEM LAB,BETHESDA,MD 20892. RI LILLY, BRENDA/N-6867-2015 OI LILLY, BRENDA/0000-0002-3125-7496 NR 46 TC 373 Z9 382 U1 1 U2 13 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD FEB 3 PY 1995 VL 267 IS 5198 BP 688 EP 693 DI 10.1126/science.7839146 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QE733 UT WOS:A1995QE73300041 PM 7839146 ER PT J AU TELFORD, SR SONG, JW YANAGIHARA, R AF TELFORD, SR SONG, JW YANAGIHARA, R TI MORE ON HANTAVIRUS IN NEW-ENGLAND AND NEW-YORK SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIH,BETHESDA,MD 20892. RP TELFORD, SR (reprint author), HARVARD UNIV,SCH PUBL HLTH,665 HUNTINGTON AVE,BOSTON,MA 02115, USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 2 PY 1995 VL 332 IS 5 BP 337 EP 337 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA QD396 UT WOS:A1995QD39600026 PM 7816081 ER PT J AU BOEUF, H MURPHY, J BIBBINS, KB VARMUS, HE AF BOEUF, H MURPHY, J BIBBINS, KB VARMUS, HE TI BINDING IN-VITRO OF PHOSPHOTYROSINE-CONTAINING PROTEINS TO PP60(C-SRC) SH2 DOMAIN DOES NOT CORRELATE WITH CEF CELL-TRANSFORMATION SO ONCOGENE LA English DT Article DE SH2; SH3; SRC; TRANSFORMATION; PHOSPHOTYROSINE ID GTPASE-ACTIVATING PROTEIN; GROWTH-FACTOR RECEPTORS; SRC HOMOLOGY REGION-2; C-SRC; V-SRC; SIGNAL TRANSDUCTION; PP60(SRC) SUBSTRATE; DEPENDENT MANNER; TYROSINE KINASE; HIGH-AFFINITY AB We have previously described pp60(c-src) SH2 mutants that are host-range-dependent for cell transformation; most of these mutants can transform CEF cells but not NIH3T3 cells, and others transform NM3T3 cells more efficiently than CEF (Hirai and Varmus, 1990c). In an attempt to understand the molecular basis of these phenotypes, we analysed the ability of mutant SH2 domains in GST fusion-proteins to bind to tyrosine phosphorylated proteins in lysates from CEF and NIH3T3 cells. The relative affinity of mutated versions of the SH2 domain for phosphotyrosine-containing proteins from CEF and NM3T3 cells was compared with the relative ability of the mutant Src proteins to transform the two cell types. While the affinity of the SH2 domain for phosphotyrosine-containing proteins was closely correlated with transformation in NIH3T3 cells, there was no correlation between phosphotyrosine binding and transformation of CEF cells, and none of the host range mutant SH2 domains showed significant differences in their ability to bind phosphotyrosine-containing proteins from lysates from either cell type. In addition, the SH3 domain was shown to augment the capacity of mutant SH2 domain to bind phosphotyrosine-containing proteins. C1 CU,STRASBOURG,FRANCE. CHIRON CORP,DEPT VIROL,EMERYVILLE,CA 94608. UNIV CALIF SAN FRANCISCO,DEPT MICROBIOL & IMMUNOL,SAN FRANCISCO,CA 94143. NIH,BETHESDA,MD 20892. RP BOEUF, H (reprint author), IGBMC,BP 163,F-67404 ILLKIRCH GRAFFENS,FRANCE. NR 57 TC 5 Z9 5 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 2 PY 1995 VL 10 IS 3 BP 433 EP 438 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA QF648 UT WOS:A1995QF64800003 PM 7531318 ER PT J AU MATOCHIK, JA MOLCHAN, SE ZAMETKIN, AJ WARDEN, DL SUNDERLAND, T COHEN, RM AF MATOCHIK, JA MOLCHAN, SE ZAMETKIN, AJ WARDEN, DL SUNDERLAND, T COHEN, RM TI REGIONAL CEREBRAL GLUCOSE-METABOLISM IN AUTOPSY-CONFIRMED CREUTZFELDT-JAKOB-DISEASE SO ACTA NEUROLOGICA SCANDINAVICA LA English DT Note DE CREUTZFELDT-JAKOB DISEASE; POSITRON EMISSION TOMOGRAPHY; GLUCOSE METABOLISM; PRION DISEASE; ENCEPHALOPATHY; DEMENTIA ID POSITRON EMISSION TOMOGRAPHY AB Regional cerebral glucose metabolism was measured in a 72-year-old man, with Creutzfeldt-Jakob disease (CJD), by positron emission tomography using [F-18]-2-fluoro-2-deoxy-D-glucose as the tracer. The diagnosis of CJD, a rare neurodegenerative disorder, was confirmed at autopsy 13 months later. Compared with five unaffected elderly men, the patient had reduced metabolism heterogeneously distributed throughout the brain. The hypometabolism was most evident in the right hemisphere, particularly in the posterior frontal, parietal, Sylvian, and temporal regions. This left-right asymmetry is more extensive than that previously reported in Alzheimer's disease, and may provide a useful metabolic marker for early diagnosis of CJD. C1 NIMH,CLIN SCI LAB,GERIATR PSYCHIAT SECT,BETHESDA,MD 20892. WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. RP MATOCHIK, JA (reprint author), NIMH,CEREBRAL METAB LAB,CLIN BRAIN IMAGING SECT,BLDG 10,ROOM 4N317,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 13 TC 10 Z9 10 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-6314 J9 ACTA NEUROL SCAND JI Acta Neurol. Scand. PD FEB PY 1995 VL 91 IS 2 BP 153 EP 157 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA QR036 UT WOS:A1995QR03600013 PM 7785428 ER PT J AU MAGNO, BV DATILES, MB LASA, MSM AF MAGNO, BV DATILES, MB LASA, MSM TI PROGRESSION OF LENS OPACITIES IN CATARACT PATIENTS AFTER ONE-YEAR SO ACTA OPHTHALMOLOGICA SCANDINAVICA LA English DT Article DE CATARACT CLASSIFICATION; PROGRESSION RATES; LONGITUDINAL STUDIES; PERSON-SPECIFIC DATA; LOCS II ID CLASSIFICATION-SYSTEM-III; LOCS-II AB We used the Lens Opacities Classification System II to clinically grade the lenses of 57 patients with age-related cataracts in at least one eye. Progression or regression in each lens region was defined as a one or more step change in the Lens Opacities Classification System II grading noted at 1 year and maintained at the 1 1/2 to 2 year visit (the validation visit). A validated change in a lens region in one eye of a patient was considered a change in that region for that patient. Person-specific rates of cataract progression at 1 year were 42% for nuclear, 32% for cortical and 10% for posterior subcapsular opacities. Corresponding regression rates were 5%, 4%, and 2% for nuclear, cortical and posterior subcapsular opacities, respectively, Progression rates were significantly greater than the regression rates only for nuclear and cortical opacities (p < 0.0005). These findings show the applicability of the clinical Lens Opacities Classification System II method in documenting and monitoring lens changes over time. The usefulness of person-specific analysis was also shown. RP MAGNO, BV (reprint author), NEI,OPHTHALM GENET & CLIN SERV BRANCH,BLDG 10,ROOM 10N226,10 CTR DR,MSC 1860,BETHESDA,MD 20892, USA. OI Datiles, Manuel III B./0000-0003-4660-1664 NR 12 TC 9 Z9 9 U1 0 U2 0 PU SCRIPTOR PUBLISHER PI HVIDOVRE PA SOVANGSVEJ 1-5, DK-2650 HVIDOVRE, DENMARK SN 1395-3907 J9 ACTA OPHTHALMOL SCAN JI Acta Ophthalmol. Scand. PD FEB PY 1995 VL 73 IS 1 BP 45 EP 49 PG 5 WC Ophthalmology SC Ophthalmology GA RA550 UT WOS:A1995RA55000010 PM 7627758 ER PT J AU LEVAV, M CRUZ, ME MIRSKY, AF AF LEVAV, M CRUZ, ME MIRSKY, AF TI EEC ABNORMALITIES, MALNUTRITION, PARASITISM AND GOITER - A STUDY OF SCHOOLCHILDREN IN ECUADOR SO ACTA PAEDIATRICA LA English DT Article DE EEG; GOITER; MALNUTRITION; PARASITE INFECTION AB We report on data collected in a sample of 194 schoolchildren (9-13 years of age) residing in a mountainous community in Ecuador. This study was part of an ongoing epidemiological inquiry into the prevalence of parasitism, malnutrition, neurocysticercosis, goitre, iodine levels and EEG abnormalities, and the relationships among these factors. Data were obtained by a local medical team supported by specialized personnel. The results showed that 34% of the EEG tracings were abnormal, with higher rates among girls. The best fitted log-linear model to explain the results was the combination of EEG status, parasite infection, goitre and gender. The best predictor of EEG abnormalities was found to be a diagnosis of goitre. C1 ACAD ECUATORIANA NEUROCIENCIAS,QUITO,ECUADOR. RP LEVAV, M (reprint author), NIMH,PSYCHOL & PSYCHOPATHOL LAB,BLDG 10,ROOM 4C110,10 CTR DR MSC 1366,BETHESDA,MD 20892, USA. NR 30 TC 6 Z9 6 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD FEB PY 1995 VL 84 IS 2 BP 197 EP 202 DI 10.1111/j.1651-2227.1995.tb13609.x PG 6 WC Pediatrics SC Pediatrics GA QJ607 UT WOS:A1995QJ60700019 PM 7756808 ER PT J AU KOZLOWSKI, LT HENNINGFIELD, JE AF KOZLOWSKI, LT HENNINGFIELD, JE TI THINKING THE UNTHINKABLE - THE PROSPECT OF REGULATION OF NICOTINE IN CIGARETTES BY THE UNITED-STATES-GOVERNMENT SO ADDICTION LA English DT Editorial Material C1 NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. RP KOZLOWSKI, LT (reprint author), PENN STATE UNIV,PROGRAM BIOBEHAV HLTH,104 DAVEY LAB,UNIVERSITY PK,PA 16802, USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXON, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD FEB PY 1995 VL 90 IS 2 BP 165 EP 167 DI 10.1111/j.1360-0443.1995.tb01024.x PG 3 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA QJ239 UT WOS:A1995QJ23900002 PM 7703812 ER PT J AU SIMPSON, RM HUBBARD, BS ALLING, DW TELLER, R FAIN, MA BOWERS, FS KINDT, TJ AF SIMPSON, RM HUBBARD, BS ALLING, DW TELLER, R FAIN, MA BOWERS, FS KINDT, TJ TI RABBITS TRANSFUSED WITH HUMAN-IMMUNODEFICIENCY-VIRUS TYPE 1-INFECTED BLOOD DEVELOP IMMUNE-DEFICIENCY WITH CD4(+) LYMPHOCYTOPENIA IN THE ABSENCE OF CLEAR EVIDENCE FOR HIV TYPE-1 INFECTION SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID CD4+ T-LYMPHOCYTOPENIA; SMALL ANIMAL-MODEL; SCID-HU MOUSE; LYMPH-NODES; CELL; PATHOGENESIS; INDIVIDUALS; EXPRESSION; ANTIBODIES; DISEASE AB Rabbits can be infected with human immunodeficiency virus (HIV-1), but no disease signs similar to acquired immunodeficiency syndrome (AIDS) have been reported to date. In our attempt to develop types of HIV-1 more virulent for rabbits, an immunodeficiency characterized by CD4(+) lymphocytopenia and opportunistic infection was induced by transfusion from HIV-l-infected rabbits. The original donor was infected for 27 months; initial passage resulted in infection of two rabbits. Transfusions from these two infected rabbits caused immunodeficiency in 12 recipients. One rabbit died at 3 months and a second at 8 months posttransfusion with lymphocyte depletion in lymphoid organs; one of these and another of the CD4(+) lymphocytopenic rabbits had opportunistic infections. Lentivirus-like particles were detected in thymus and spleen from an affected rabbit. Despite appearance of AIDS-like disease signs, antibodies to HIV-1 proteins were not detected in rabbits receiving passaged blood. However, RNA transcripts hybridizing with HIV-1 probes were detected in organs of some rabbits, implicating the initial HIV infection in the disease. Transfusion from uninfected donors produced no signs of immunodeficiency, which suggests the involvement of an HIV-related agent. The present data do not allow definitive characterization of the agent(s) involved in the immunodeficiency. Possibilities include activation of a rabbit retrovirus or, alternatively, development of a mutated HIV-I strain. C1 NIAID,BETHESDA,MD 20892. RP SIMPSON, RM (reprint author), NIAID,TWINBROOK 2 FACIL,IMMUNOGENET LAB,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. NR 45 TC 4 Z9 4 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 FEB PY 1995 VL 11 IS 2 BP 297 EP 306 DI 10.1089/aid.1995.11.297 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA QJ888 UT WOS:A1995QJ88800012 PM 7742043 ER PT J AU FRANCHINI, G TARTAGLIA, J MARKHAM, P BENSON, J FULLEN, J WILLS, M ARP, J DEKABAN, G PAOLETTI, E GALLO, RC AF FRANCHINI, G TARTAGLIA, J MARKHAM, P BENSON, J FULLEN, J WILLS, M ARP, J DEKABAN, G PAOLETTI, E GALLO, RC TI HIGHLY ATTENUATED HTLV TYPE I-ENV POXVIRUS VACCINES INDUCE PROTECTION AGAINST A CELL-ASSOCIATED HTLV TYPE-I CHALLENGE IN RABBITS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID VIRUS TYPE-I; FELINE LEUKEMIA-VIRUS; RETROVIRUS; SEQUENCE; RECOMBINANT; INFECTION; ENVELOPE; GENE; LYMPHOMA; VARIANT AB The entire envelope protein of the human T cell leukemia/lymphoma virus type I (HTLV-I)(1711), obtained from the DNA of a West African healthy HTLV-I-infected patient, was expressed in the highly attenuated poxvirus vaccine vectors ALVAC and NYVAC. These live recombinant vaccine candidates were used to immunize New Zealand White rabbits. Immunization regimens included inoculation of the poxvirus recombinant alone as well as prime/boost protocols using gp63 HTLV-I envelope precursor protein in Alum as the subunit boost. All animals were exposed to an HTLV-I cell-associated challenge (5 x 10(4) cells) from a primary culture of the HTLV-I-BOU isolate. The results indicated that two inoculations of the ALVAC-based HTLV-I-env vaccine candidate protected animals against viral challenge 5 months following the last immunization. However, a combination protocol with ALVAC-env and two additional boosts of gp63 surprisingly failed to confer protection, suggesting that administration of the subunit preparation might be deleterious. Further, in the case of the NYVAC HTLV-I-env recombinant, protection was afforded as early as 2 months following the first immunization. Last, all the protected animals in the NYVAC and ALVAC trials were challenged 5 months following the initial challenge exposure with 5 mi of blood from an HTLV-I-BOU-infected animal, and subsequently became infected. Protection conferred by the attenuated HTLV-I-env recombinant poxvirus vaccine in the rabbit model might be instrumental for optimizing the immunogenicity of poxvirus-based vaccine candidates against human immunodeficiency virus (HIV), particularly because of the need to enhance protection against cell-to-cell transmission. This approach has already shown some efficacy in the HIV type 2/rhesus macaque system. C1 VIROGENET CORP,TROY,NY 12180. ADV BIOSCI LABS INC,KENSINGTON,MD 20895. JOHN P ROBARTS RES INST,LONDON,ON N6A 5K8,CANADA. RP FRANCHINI, G (reprint author), NCI,TUMOR CELL BIOL LAB,BLDG 37,ROOM 6A01,37 CONVENT DR MSC 4255,BETHESDA,MD 20892, USA. NR 37 TC 33 Z9 33 U1 0 U2 1 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 FEB PY 1995 VL 11 IS 2 BP 307 EP 313 DI 10.1089/aid.1995.11.307 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA QJ888 UT WOS:A1995QJ88800013 PM 7742044 ER PT J AU ISAKI, L AF ISAKI, L TI INTRODUCTION TO THE SYMPOSIUM SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Editorial Material RP ISAKI, L (reprint author), NIAAA,6000 ROCKVILLE PIKE,ROCKVILLE,MD 20892, USA. NR 6 TC 0 Z9 0 U1 0 U2 0 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 FEB PY 1995 VL 19 IS 1 BP 1 EP 2 DI 10.1111/j.1530-0277.1995.tb01463.x PG 2 WC Substance Abuse SC Substance Abuse GA QG625 UT WOS:A1995QG62500001 ER PT J AU DAWSON, DA GRANT, BF HARFORD, TC AF DAWSON, DA GRANT, BF HARFORD, TC TI VARIATION IN THE ASSOCIATION OF ALCOHOL-CONSUMPTION WITH 5 DSM-IV ALCOHOL PROBLEM DOMAINS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ALCOHOL CONSUMPTION; HEAVY DRINKING; ALCOHOL PROBLEMS; ALCOHOL ABUSE; DEPENDENCE ID FAMILY HISTORY; HEAVY-DRINKING; DEPENDENCE; RISK; INTOXICATION AB Data from a nationally representative sample of the U.S. adult population were used to investigate the association between alcohol consumption and five discrete problem domains included in the DSM-IV formulations for alcohol abuse and dependence. Two dimensions of consumption were considered in the analysis: average daily ethanol intake and the relative frequency of drinking five or more drinks. The sample consisted of 22,102 adults defined as current drinkers. After controlling for various sociodemographic characteristics, family history of alcoholism, and age at onset of drinking, both consumption measures retained significant levels of association within all five problem domains. The magnitudes of the odds ratios at selected levels of consumption were similar to 50% greater for the domains of impaired control, continued drinking despite problems and hazardous drinking than for the domains of tolerance and withdrawal. Moreover, the factors that modified the effect of the consumption measures varied markedly across domains, with age, college education, and race the most consistent modifiers of the effect of alcohol consumption. RP DAWSON, DA (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,6000 EXEC BLVD,ROCKVILLE,MD 20892, USA. NR 34 TC 31 Z9 32 U1 0 U2 3 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 FEB PY 1995 VL 19 IS 1 BP 66 EP 74 PG 9 WC Substance Abuse SC Substance Abuse GA QG625 UT WOS:A1995QG62500012 PM 7771666 ER PT J AU CHAO, HM AF CHAO, HM TI ALCOHOL AND THE MYSTIQUE OF FLUSHING SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article ID MITOCHONDRIAL ALDEHYDE DEHYDROGENASE; NORTH-AMERICAN INDIANS; METABOLIZING ENZYMES; ETHNIC-DIFFERENCES; GENETIC VARIATIONS; ASIAN MEN; JAPANESE; ETHANOL; SENSITIVITY; ALDH2 RP CHAO, HM (reprint author), NIAAA, DIV BASIC RES, 6000 EXEC BLVD, ROCKVILLE, MD 20892 USA. NR 50 TC 24 Z9 24 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 1995 VL 19 IS 1 BP 104 EP 109 DI 10.1111/j.1530-0277.1995.tb01477.x PG 6 WC Substance Abuse SC Substance Abuse GA QG625 UT WOS:A1995QG62500017 PM 7771635 ER PT J AU TEIEN, D JONES, M SHIOTA, T YAMADA, I SAHN, DJ AF TEIEN, D JONES, M SHIOTA, T YAMADA, I SAHN, DJ TI RELATION OF LEFT ATRIAL V-WAVE LEFT-VENTRICULAR SYSTOLIC PRESSURE RATIO TO MITRAL REGURGITANT VOLUME SO AMERICAN HEART JOURNAL LA English DT Article ID QUANTIFICATION AB Evaluation of mitral regurgitation is difficult whether invasive or noninvasive methods are used. The determination of the regurgitant volume itself cannot be done in clinical practice with reasonable accuracy. In six sheep with chronic mitral regurgitation, left ventricular and left atrial pressures were recorded with high-fidelity catheters. The regurgitant volume was measured directly with electromagnetic flow probes positioned at the mitral annulus and around the ascending aorta, balanced against each other. A total of 24 hemodynamic states were obtained varying preload and afterload by fluid expansion and angiotensin infusion. On the basis of these studies, the pressure ratio of the V wave divided by the left ventricular systolic pressure is proposed as an index of regurgitant volume. A good correlation was found between this ratio and the regurgitant volume (r = 0.75). The ratio is easily recorded during routine heart catheterization. C1 OREGON HLTH SCI UNIV,CLIN CARE CTR CONGENITAL HEART DIS,PORTLAND,OR 97201. NHLBI,ANIM MED & SURG LAB,BETHESDA,MD. NR 10 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD FEB PY 1995 VL 129 IS 2 BP 282 EP 284 DI 10.1016/0002-8703(95)90009-8 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA QE518 UT WOS:A1995QE51800010 PM 7832100 ER PT J AU GILLIGAN, DM BADAR, DM PANZA, JA QUYYUMI, AA CANNON, RO AF GILLIGAN, DM BADAR, DM PANZA, JA QUYYUMI, AA CANNON, RO TI EFFECTS OF ESTROGEN REPLACEMENT THERAPY ON PERIPHERAL VASOMOTOR FUNCTION IN POSTMENOPAUSAL WOMEN SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY HEART-DISEASE AB Hormone replacement therapy is associated with a reduction in cardiovascular events in postmenopausal women. We have recently found that acute 17 beta-estradiol administration improves endothelium-dependent vasodilation in both the peripheral and coronary circulations of postmenopausal women. The current study was undertaken in 33 estrogen-deficient postmenopausal women (mean age 59 +/- 7 years) to determine if short term estrogen replacement therapy also improves endothelium-dependent vasodilation in peripheral circulation. Acute intraarterial infusion of estradiol, which increased forearm venous estradiol levels from 16 +/- 11 to 345 +/- 202 pg/ml, potentiated forearm vasodilation induced by the endothelium-dependent vasodilator acetylcholine by 49 +/- 67% (p <0.001). Acute estradiol also potentiated vasodilation induced by the endothelium-independent vasodilator nitroprusside by 5 +/- 31% (p = 0.04). However, after 3 weeks of transdermal estradiol administration (0.1 mg/day), which achieved an estradiol level of 120 +/- 57 pg/ml, the vasodilator responses to acetylcholine and to sodium nitroprusside were unchanged from initial measurements obtained before acute administration of estradiol, Repeat intraarterial infusion of estradiol in 8 women, while receiving transdermal estradiol, increased forearm venous estradiol levels to 268 +/- 105 pg/ml and again potentiated the vasodilator response to acetylcholine to a similar degree as that observed in the initial study after acute administration of estradiol. Thus, although acute intraarterial infusion of 17 beta-estradiol potentiates endothelium-dependent vasodilation in the forearms of postmenopausal women, this effect is not maintained with a 3-week cycle of systemic estradiol administration. The different effects of acute and chronic estradiol may be due to the lower plasma levels achieved with chronic estrogen administration. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NR 12 TC 131 Z9 132 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB 1 PY 1995 VL 75 IS 4 BP 264 EP 268 DI 10.1016/0002-9149(95)80033-O PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA QD397 UT WOS:A1995QD39700012 PM 7832136 ER PT J AU HAMBIDGE, KM BALLARDBARBASH, R CHAIR, A CLARK, NG HOWARD, L JENSEN, GL KREBS, NF BISTRIAN, BR KUSHNER, RF YOUNG, EA AF HAMBIDGE, KM BALLARDBARBASH, R CHAIR, A CLARK, NG HOWARD, L JENSEN, GL KREBS, NF BISTRIAN, BR KUSHNER, RF YOUNG, EA TI THE ROLE AND IDENTITY OF PHYSICIAN NUTRITION SPECIALISTS IN MEDICAL SCHOOL-AFFILIATED HOSPITALS SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE PHYSICIAN NUTRITION SPECIALIST; MEDICAL SCHOOL-AFFILIATED HOSPITALS; NUTRITION EDUCATION ID CLINICAL-NUTRITION; TRAINING-PROGRAMS; EDUCATION AB This document was prepared by the Committee on Clinical Practice Issues in Health and Disease of The American Society for Clinical Nutrition (ASCN). The committee recommends that each major medical center has at least one physician nutrition specialist (PNS) who will be a regional resource for complex nutrition cases and will have a leadership role in the provision of coordinated nutrition services. The PNS will be responsible for nutrition education programs in associated schools of medicine and will be a role model for aspiring physicians. Typically, these individuals will have thorough training in human nutrition research. The PNS should be supported by a unique combination of resources including clinical earnings, teaching hospital and school of medicine salaries, state and federal funds, as well as private sector support. The ASCN should take a leadership role in developing the national identity of the PNS and in achieving recognition of board certification in nutrition. C1 AMER SOC CLIN NUTR,SECRETARIAT OFF,BETHESDA,MD. NCI,BETHESDA,MD 20892. UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98195. BAYSTATE MED CTR,SPRINGFIELD,MA 01199. ALBANY MED CTR,DEPT MED,ALBANY,NY 12208. GEISINGER MED CTR,DEPT GASTROENTEROL,DANVILLE,PA 17822. GEISINGER MED CTR,DEPT NUTR,DANVILLE,PA 17822. NEW ENGLAND DEACONESS HOSP,NUTR SUPPORT SERV,BOSTON,MA 02215. UNIV CHICAGO,DEPT MED,CHICAGO,IL 60637. UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV HUMAN NUTR,SAN ANTONIO,TX 78284. RP HAMBIDGE, KM (reprint author), UNIV COLORADO,HLTH SCI CTR,DEPT PEDIAT,NUTR SECT,4200 E 9TH AVE,BOX C225,DENVER,CO 80262, USA. NR 17 TC 14 Z9 14 U1 0 U2 0 PU AMER SOC CLIN NUTRITION INC 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 FEB PY 1995 VL 61 IS 2 BP 264 EP 268 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA QD951 UT WOS:A1995QD95100002 ER PT J AU WINN, DM AF WINN, DM TI DIET AND NUTRITION IN THE ETIOLOGY OF ORAL-CANCER SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Nutritional Aspects of Oral Health - New Perspectives, at the Joint Meeting of the IADR/AADR Nutrition-Group/Biochemistry-and-Nutrition-Section of the American-Association-of-Dental-Schools CY MAR 10, 1993 CL CHICAGO, IL SP INT ASSOC DENTAL RES, NUTR GRP, AMER ASSOC DENTAL RES, NUTR GRP DE EPIDEMIOLOGY; DIET; MOUTH NEOPLASMS; CHEMOPREVENTION; ALCOHOL ID SQUAMOUS-CELL CARCINOMA; VITAMIN SUPPLEMENT USE; PHARYNGEAL CANCER; BETA-CAROTENE; UNITED-STATES; ALCOHOLIC BEVERAGE; ESOPHAGEAL CANCER; SUBSEQUENT RISK; BREAST-CANCER; CAVITY AB Epidemiological studies worldwide have implicated dietary and nutritional factors in the development of oral and pharyngeal cancer. Dietary information in these case-control studies generally was collected through food-frequency questionnaires. Consistently, these studies observed a protective effect of a diet high in fruit intake, reflected in a 20-80% reduction in oral cancer risk. A high intake of foods considered to be dietary staples in particular cultural groups, possibly indicating a generally impoverished diet, has been linked to excess risk. Indigenous dietary practices that in single studies were found to increase risk include a high intake of chili powder and wood stove cooking. Supplementation with various vitamins has been protective in a few studies. Chemoprevention trials generally have found that chemopreventive agents reduce the size of oral leukoplakia lesions or the frequency of second primary oral cancers. The most consistent dietary findings across multiple cultural settings are a protective effect of high fruit consumption and the carcinogenic effect of high alcohol intake. C1 NIDR, ORAL DIS PREVENT PROGRAM, BETHESDA, MD 20892 USA. RP WINN, DM (reprint author), NIDR, DIV EPIDEMIOL, NATCHER BLDG MSC 6401, BETHESDA, MD 20892 USA. NR 75 TC 30 Z9 31 U1 3 U2 3 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD FEB PY 1995 VL 61 IS 2 BP 437S EP 445S PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA QD951 UT WOS:A1995QD95100036 PM 7840089 ER PT J AU WACHOLDER, S HARTGE, P DOSEMECI, M ARMSTRONG, B AF WACHOLDER, S HARTGE, P DOSEMECI, M ARMSTRONG, B TI VALIDATION STUDIES USING AN ALLOYED GOLD STANDARD - REPLY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter C1 MCGILL UNIV,SCH OCCUPAT HLTH,MONTREAL,PQ H3A 1A3,CANADA. RP WACHOLDER, S (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,ROCKVILLE,MD 20852, USA. NR 3 TC 1 Z9 1 U1 0 U2 2 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD FEB 1 PY 1995 VL 141 IS 3 BP 277 EP 277 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QE798 UT WOS:A1995QE79800018 ER PT J AU BELLUS, GA HEFFERON, TW DELUNA, RIO HECHT, JT HORTON, WA MACHADO, M KAITILA, I MCINTOSH, I FRANCOMANO, CA AF BELLUS, GA HEFFERON, TW DELUNA, RIO HECHT, JT HORTON, WA MACHADO, M KAITILA, I MCINTOSH, I FRANCOMANO, CA TI ACHONDROPLASIA IS DEFINED BY RECURRENT G380R MUTATIONS OF FGFR3 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENE CONVERSION; GLOBIN GENE; HOMOZYGOUS ACHONDROPLASIA; POINT MUTATIONS; HEMOPHILIA-A; DISEASE; HYPOCHONDROPLASIA; TRANSITIONS; FREQUENCY; FAMILY AB Genomic DNA from 154 unrelated individuals with achondroplasia was evaluated for mutations in the fibroblast growth factor receptor 3 (FGFR3) transmembrane domain. AU but one, an atypical case, were found to have a glycine-to-arginine substitution at codon 380. Of these, 150 had a G-to-A transition at nt 1138, and 3 had a G-to-C transversion at this same position. On the basis of estimates of the prevalence of achondroplasia, the mutation rate at the FGFR3 1138 guanosine nucleotide is two to three orders of magnitude higher than that previously reported for tranversions and transitions in CpG dinucleotides. To date, this represents the most mutable single nucleotide reported in the human genome. The homogeneity of mutations in achondroplasia is unprecedented for an autosomal dominant disorder and may explain the relative lack of heterogeneity in the achondroplasia phenotype. C1 NIH,NATL CTR HUMAN GENOME RES,MED GENET BRANCH,BETHESDA,MD 20892. HOSP INFANTIL MEXICO FED GOMEZ,DEPT GENET,MEXICO CITY,DF,MEXICO. JOHNS HOPKINS UNIV,SCH MED,CTR MED GENET,BALTIMORE,MD 21205. UNIV TEXAS,SCH MED,DEPT PEDIAT,HOUSTON,TX. SHRINERS HOSP CRIPPLED CHILDRENS,DEPT RES,PORTLAND,OR 97201. HELSINKI UNIV HOSP,DEPT CLIN GENET,HELSINKI,FINLAND. FU NHGRI NIH HHS [P01HG00373]; NIAMS NIH HHS [R01AR41135]; NICHD NIH HHS [R01HD20691] NR 52 TC 258 Z9 276 U1 0 U2 10 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 FEB PY 1995 VL 56 IS 2 BP 368 EP 373 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA QF423 UT WOS:A1995QF42300002 PM 7847369 ER PT J AU STEENLAND, K BROWN, D AF STEENLAND, K BROWN, D TI MORTALITY STUDY OF GOLD MINERS EXPOSED TO SILICA AND NONASBESTIFORM AMPHIBOLE MINERALS - AN UPDATE WITH 14 MORE YEARS OF FOLLOW-UP SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE SILICA; SILICOSIS; LUNG CANCER; ASBESTOS; GOLD MINERS ID SAFETY-AND-HEALTH; LUNG-CANCER; OCCUPATIONAL COHORT; SYSTEMIC-SCLEROSIS; GRANITE WORKERS; INSTITUTE AB We have updated a study of 3,328 gold miners who worked underground for at least 1 year between 1940-1965 in South Dakota, extending the follow-up from 1977 to 1990. The exposures of concern were silica and nonasbestiform amphibole minerals. The lung cancer standardized mortality ratio (SMR) was 1.13 (95% confidence interval [CI] 0.94-1.36, 115 observed) when the U.S. population was used as the referent group, increasing to 1.25 (95% CI 1.03-1.51) when the county was used as the referent, and to 1.27 (1.02-1.55) for person-time with more than 30 years potential latency. However, lung cancer mortality did not show a positive exposure-response trend with estimated cumulative dust exposure. Data on smoking habits suggested that the miners smoked slightly more than the U.S. population in a 1960 cross-sectional survey. In contrast to lung cancer, other diseases known to be associated with silica exposure (tuberculosis and silicosis) were significantly increased (SMR = 3.44 and 2.61) and exhibited clear exposure-response trends. Nonmalignant renal disease, also associated with silica exposure, was elevated for those hired in early years and showed a significant positive exposure-response trend. Multiple-cause analysis revealed significant excesses of arthritis, musculoskeletal diseases (including systemic lupus and sclerosis), and skin conditions (including scleroderma and lupus), diseases of autoimmune origin which have been associated with silica exposure in other studies. Multiple cause analysis also showed a significant excess of diseases of the blood and blood-forming organs. (C) 1995 Wiley-Liss, Inc.* C1 NIEHS,RES TRIANGLE PK,NC 27709. RP STEENLAND, K (reprint author), NIOSH,4676 COLUMBIA PKWY,CINCINNATI,OH 45206, USA. NR 36 TC 90 Z9 92 U1 3 U2 12 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD FEB PY 1995 VL 27 IS 2 BP 217 EP 229 DI 10.1002/ajim.4700270207 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QK090 UT WOS:A1995QK09000006 PM 7755012 ER PT J AU HUFF, J AF HUFF, J TI MECHANISMS, CHEMICAL CARCINOGENESIS, AND RISK ASSESSMENT - CELL-PROLIFERATION AND CANCER SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE CARCINOGENESIS; CELL PROLIFERATION; RISK ASSESSMENT; EXPERIMENTAL CARCINOGENESIS; BIOASSAYS; ANIMAL CARCINOGENS; HUMAN CARCINOGENS ID INDUCED HEPATOCYTE PROLIFERATION; FEMALE B6C3F1 MICE; MULTISTEP CARCINOGENESIS; LIVER CARCINOGENESIS; RENAL CARCINOGENESIS; METHYLENE-CHLORIDE; ALPHA-2U-GLOBULIN; MITOGENESIS; NEPHROPATHY; EXPOSURE AB Mechanisms of carcinogenesis-and in particular chemically associated carcinogenicity-have attracted considerable scientific and public attention in the last decade. Much insight has been gained that will lead to more reasoned and better prevention, intervention, and treatment for the reduction of environmentally caused cancers. However, there seems to be an exaggerated tendency to embrace ''mechanisms'' not yet fully characterized, completely tested, unequivocally proven, and consensus accepted. More than 100 agents and exposure circumstances have been identified as causally or strongly associated with human cancers; for many the evidence was discovered first in experimental animals. More chemicals have been uncovered as carcinogenic in experimental animals, with as yet no or little available information in exposed human populations. Additional and expanded mechanistic and epidemiological studies should further elucidate the relevance of these agents to adverse human health effects, including cancers. Claims are being posed that certain chemical-specific ''mechanisms'' in experimental systems are irrelevant to humans, and thus chemicals thought to be aberrantly carcinogenic in animals would present no cancer hazard to exposed humans. Nonetheless before undeniable proof becomes available, we must continue to proceed with sensitive and responsible caution. This commentary offers a central and personal view of one such mechanism: cell proliferation and cancer. (C) 1995 Wiley-Liss, Inc.* RP HUFF, J (reprint author), NIEHS,ENVIRONM CARCINOGENESIS PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 47 TC 34 Z9 34 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD FEB PY 1995 VL 27 IS 2 BP 293 EP 300 DI 10.1002/ajim.4700270213 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QK090 UT WOS:A1995QK09000012 PM 7755018 ER PT J AU HACK, M WRIGHT, LL SHANKARAN, S TYSON, JE HORBAR, JD BAUER, CR YOUNES, N OH, W PHILIPS, JB CASSADY, G FANAROFF, AA EDWARDS, W LITTLE, G BAIN, RP VERTER, J WRIGHT, EC BANDSTRA, ES YAFFE, SJ MALLOY, M KORONES, SB COOKE, R TYSON, JE UAUY, R LUCEY, JF POLAND, RL SHANKARAN, S AF HACK, M WRIGHT, LL SHANKARAN, S TYSON, JE HORBAR, JD BAUER, CR YOUNES, N OH, W PHILIPS, JB CASSADY, G FANAROFF, AA EDWARDS, W LITTLE, G BAIN, RP VERTER, J WRIGHT, EC BANDSTRA, ES YAFFE, SJ MALLOY, M KORONES, SB COOKE, R TYSON, JE UAUY, R LUCEY, JF POLAND, RL SHANKARAN, S TI VERY-LOW-BIRTH-WEIGHT OUTCOMES OF THE NATIONAL-INSTITUTE-OF-CHILD-HEALTH-AND-HUMAN-DEVELOPMENT NEONATAL NETWORK, NOVEMBER-1989 TO OCTOBER-1990 SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE VERY LOW BIRTH WEIGHT; NEONATAL; MORBIDITY; MORTALITY ID SURFACTANT THERAPY; INTENSIVE-CARE; INFANTS; SEVERITY; SCORE AB OBJECTIVE: Our purpose was to describe the neonatal outcomes of 1804 very-low-birth-weight (less than or equal to 1500 gm) infants delivered between November 1989 and October 1990 in the participating centers of the National institute of Child Health and Human Development Neonatal Research Network. STUDY DESIGN: In an observational study sociodemographic, pregnancy, and delivery data were collected soon after birth, and neonatal and outcome data at discharge, at 120 days, or at death. RESULTS: Maternal and birth weight characteristics included 64% black, 29% white; 71% single mothers; 18% no prenatal care; 17% antenatal steroids; and 12% multiple gestations. Birth weight distributions included 18% weighing 501 to 750 gm, 23% 751 to 1000 gm, 28% 1001 to 1250 gm, and 31% 1251 to 1500 gm. Survival was 39% at <751 gm birth weight, 77% at 751 to 1000 gm, 90% at 1001 to 1250 gm, and 93% at 1251 to 1500 gm: Survival was 15% to 18% at less than or equal to 23 weeks' gestation, 54% at 24 weeks, 59% at 25 weeks, and 71% at 26 weeks. Surfactant was administered to 45% of the 56% of infants with respiratory distress syndrome. Morbidity, including intraventricular hemorrhage (40%), septicemia (24%), symptomatic patent ductus arteriosus (22%), and necrotizing entercolitis (8%), increased with decreasing birth weight. Oxygen was administered for greater than or equal to 28 days to 82% of <751 gm infants, 49% of 751 to 1000 gm infants, and 10% of >1001 gm infants. Steroids were administered to 28% of infants who required oxygen for greater than or equal to 28 days. Mean hospital stay was 62 days for survivors and 18 days for infants who died. There were large intercenter variations in mortality and morbidity. CONCLUSION: Mortality and morbidity in very-low-birth-weight infants improved in 1989 to 1990 without an increase in morbidity or length of hospital stay. The threshold of the improved survival was greater than or equal to 24 weeks and 601 to 700 gm. Although such data are reassuring, the rate of major morbidity in <1001 gm birth weight infants continues to be high. C1 CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. NICHHD,BETHESDA,MD 20892. WAYNE STATE UNIV,DETROIT,MI 48202. UNIV VERMONT,BURLINGTON,VT. UNIV TEXAS,SW MED CTR,DALLAS,TX. UNIV MIAMI,MIAMI,FL 33152. GEORGE WASHINGTON UNIV,CTR BIOSTAT,ROCKVILLE,MD. FU NICHD NIH HHS [U10 HD21385, U10 HD21364, U10 HD21373] NR 19 TC 136 Z9 145 U1 1 U2 4 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD FEB PY 1995 VL 172 IS 2 BP 457 EP 464 DI 10.1016/0002-9378(95)90557-X PN 1 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA QJ328 UT WOS:A1995QJ32800001 PM 7856670 ER PT J AU SIBAI, BM GORDON, T THOM, E CARITIS, SN KLEBANOFF, M MCNELLIS, D PAUL, RH GODFREY, S ROSEN, M CHAO, R GREEN, JD WITTER, F ROCCO, L JEFFERSON, T DEPP, R TANNENBAUM, S CEFALO, RC COTRONEO, M WALLA, C MERCER, BM BRAY, E ROMERO, R HOBBINS, JC SABO, G YAFFE, S CATZ, C AF SIBAI, BM GORDON, T THOM, E CARITIS, SN KLEBANOFF, M MCNELLIS, D PAUL, RH GODFREY, S ROSEN, M CHAO, R GREEN, JD WITTER, F ROCCO, L JEFFERSON, T DEPP, R TANNENBAUM, S CEFALO, RC COTRONEO, M WALLA, C MERCER, BM BRAY, E ROMERO, R HOBBINS, JC SABO, G YAFFE, S CATZ, C TI RISK-FACTORS FOR PREECLAMPSIA IN HEALTHY NULLIPAROUS WOMEN - A PROSPECTIVE MULTICENTER STUDY SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE RISK FACTORS; NULLIPAROUS; PREECLAMPSIA ID BLOOD-PRESSURE; PRE-ECLAMPSIA; PREGNANCY; HYPERTENSION; ABORTION; SMOKING AB OBJECTIVE: We conducted a large clinical trial to evaluate the effect of low-dose aspirin on the frequency of preeclampsia in nulliparous women. A secondary objective of the trial was to identify those clinical characteristics that might be predictive for the development of preeclampsia. STUDY DESIGN: A total of 2947 healthy women with a single fetus were prospectively followed up from randomization at 13 to 27 weeks' gestation to the end of pregnancy. Of these, 1465 women were assigned to low-dose aspirin and 1482 to placebo. Baseline maternal blood pressure and demographic characteristics were examined for the prediction of preeclampsia. RESULTS: Preeclampsia developed in 156 women (5.3%). Four characteristics predicted the development of preeclampsia: in order of importance, systolic blood pressure at entry, prepregnancy obesity (weight as a percentage of desirable weight), number of previous abortions or miscarriages, and smoking history. Contrary to previous reports, black race was not a risk factor for preeclampsia. Systolic blood pressure was a better predictor of preeclampsia than either diastolic or mean arterial blood pressure. The greater the blood pressure or prepregnancy weight, the greater was the risk for preeclampsia. If the woman had never smoked or had never been previously pregnant, her risk was also higher than average. A multivariate logistic regression equation based on these four factors was able to define a tenth of the population at very high risk and another tenth at very low risk; the ratio of risk between these two groups was 12:1. The p value for each of the multivariate coefficients of the risk equation was systolic blood pressure (p < 0.001), prepregnancy weight (p < 0.01), smoking history (p < 0.01), and gravidity (p < 0.05). There were no statistically significant differences in the predictive values of these risk factors between women receiving low-dose aspirin or placebo. CONCLUSIONS: These risk factors should be of value to practitioners counseling women regarding preeclampsia. Moreover, such risk factors should be considered in the design of future studies dealing with preeclampsia. C1 GEORGE WASHINGTON UNIV,CTR BIOSTAT,WASHINGTON,DC 20052. UNIV PITTSBURGH,MAGEE WOMENS HOSP,PITTSBURGH,PA 15260. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. NICHHD,BETHESDA,MD 20892. RP SIBAI, BM (reprint author), UNIV TENNESSEE,DEPT OBSTET & GYNECOL,853 JEFFERSON,SUITE E102,MEMPHIS,TN 38103, USA. OI caritis, steve/0000-0002-2169-0712 FU NICHD NIH HHS [HD 21366, HD 21410, HD 21434] NR 21 TC 310 Z9 320 U1 1 U2 8 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD FEB PY 1995 VL 172 IS 2 BP 642 EP 648 DI 10.1016/0002-9378(95)90586-3 PN 1 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA QJ328 UT WOS:A1995QJ32800030 PM 7856699 ER PT J AU AMIN, KM LITZKY, LA SMYTHE, WR MOONEY, AM MORRIS, JM MEWS, DJY PASS, HI KARI, C RODECK, U RAUSCHER, FJ KAISER, LR ALBELDA, SM AF AMIN, KM LITZKY, LA SMYTHE, WR MOONEY, AM MORRIS, JM MEWS, DJY PASS, HI KARI, C RODECK, U RAUSCHER, FJ KAISER, LR ALBELDA, SM TI WILMS-TUMOR-1 SUSCEPTIBILITY (WT1) GENE-PRODUCTS ARE SELECTIVELY EXPRESSED IN MALIGNANT MESOTHELIOMA SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CELL-SUBSTRATUM ADHESION; SUPPRESSOR; RECEPTORS; TISSUES; PROTEIN; LOCUS AB The distinction between malignant Mesothelioma and other neoplastic processes involving the pleura is difficult, partly due to the lack of specific markers expressed on mesothelioma. Because of evidence suggesting that the Wilms' tumor susceptibility gene (WT1), unlike other tumor suppressor genes, is restricted mostly to mesenchymally derived tissues, we hypothesized that the WT1 gene products could serve as a potential marker for mesothelioma. The expression of WT1 mRNA was analyzed in 19 malignant mesothelioma cell lines and 9 tumors and compared with the expression of WT1 in 10 non-small cell lung cancer lines and 9 lung cancer specimens, WT1 mRNA was detectable by Northern analysis in 16 of 19 mesothelioma cell lines and in 5 of 8 malignant mesothelioma tumors. In contrast, WT1 mRNA was not detected by Northern analysis in non-small cell lung cancer lines or carcinomas. Immunoprecipitation with an anti-WT1 monoclonal antibody showed that a 52- to 54-kd protein was present in 4 mesothelioma cell lines. Immunostaining with this antibody localized the WT1 protein to the nucleus in two mesothelioma lines and in 20 of 21 mesothelioma tumors examined. This distinctive pattern of nuclear immunoreactivity was absent in 26 non-mesothelioma tumors involving the lung, including 20 non-small cell lung carcinomas. The detection of WT1 mRNA or protein may thus provide a specific molecular or immunohistochemical marker for differentiation of mesothelioma from other pleural tumors, in particular, adenocarcinoma. C1 UNIV PENN,MED CTR,DEPT MED,DIV PULM & CRIT CARE,PHILADELPHIA,PA 19104. UNIV PENN,MED CTR,DEPT SURG,PHILADELPHIA,PA 19104. UNIV PENN,MED CTR,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104. NCI,THORAC ONCOL SECT,BETHESDA,MD 20892. FU NCI NIH HHS [CA25871, CA47983, CA52009] NR 40 TC 152 Z9 153 U1 0 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 FEB PY 1995 VL 146 IS 2 BP 344 EP 356 PG 13 WC Pathology SC Pathology GA QF427 UT WOS:A1995QF42700007 PM 7856747 ER PT J AU KWON, ED JUNG, KY EDSALL, LC KIM, HY GARCIAPEREZ, A BURG, MB AF KWON, ED JUNG, KY EDSALL, LC KIM, HY GARCIAPEREZ, A BURG, MB TI OSMOTIC REGULATION OF SYNTHESIS OF GLYCEROPHOSPHOCHOLINE FROM PHOSPHATIDYLCHOLINE IN MDCK CELLS SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE ORGANIC OSMOLYTES; LYSOPHOSPHATIDYLCHOLINE; PHOSPHATIDYLCHOLINE CATABOLISM ID ORGANIC OSMOLYTE GLYCEROPHOSPHORYLCHOLINE; COLLECTING DUCT CELLS; PHOSPHOLIPASE-B; CULTURED-CELLS; RENAL-CELLS; RAT-LIVER; METABOLISM; LYSOPHOSPHATIDYLCHOLINE; BIOSYNTHESIS; MEMBRANE AB Glycerophosphocholine (GPC) is osmotically regulated in renal medullary cells and in cultured Madin-Darby canine kidney (MDCK) cells. Previously, it was shown that a high extracellular concentration of urea or NaCl causes these cells to accumulate large amounts of GPC. GPC is known to be a product of phosphatidylcholine (PC) catabolism. The purpose of the present experiments was to examine the role of changes in the rate of GPC synthesis from PC in hyperosmotically induced GPC accumulation. When 1-palmitoyl-2-lysophosphatidyl-[methyl-H-3]choline ([H-3]LPC) is added to the medium, it is taken up by the cells and most of it is rapidly converted to PC. During a chase, H-3 lost from PC appears almost exclusively in GPC and sphingomyelin. The rate of catabolism of PC is twofold greater in cells exposed to high NaCl (200 mosmol/kgH(2)O, added for 2 days) than in control or high-urea medium. Increased PC catabolism in NaCl-treated cells is associated with a 2.6-fold increase in GPC synthesis from PC; sphingomyelin synthesis decreases, and total cell PC does not change. Also, neither total mass nor specific radioactivity of lysophosphatidylcholine changes. PC catabolism is unaffected by short (2 h) exposure to high NaCl or urea. To investigate the enzymatic basis for the increased PC catabolism in response to high NaCl, phospholipase activity was measured in cell homogenates with 1-palmitoyl-2-[1-C-14]palmitoyl-PC as a substrate. Exposure of cells to high NaCl for 2 days (but not 2 h) increases activity 2.8-fold compared with control or high-urea medium. Lysophospholipase activity (measured with [H-3]LPC as the substrate) is unchanged. The increased phospholipase activity occurs with dipalmitoyl PC, but not sn-2-arachidonyl PC, as a substrate. Collectively, these data suggest a role for a phospholipase, unrelated to the arachidonyl-selective enzyme, in the regulation of PC catabolism during accumulation of GPC induced by prolonged exposure to high extracellular NaCl. C1 NHLBI, KIDNEY & ELECTROLYTE METAB LAB, BETHESDA, MD 20892 USA. NIAAA, BETHESDA, MD 20892 USA. NR 51 TC 29 Z9 30 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 EI 1522-1563 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD FEB PY 1995 VL 268 IS 2 BP C402 EP C412 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA QF550 UT WOS:A1995QF55000016 PM 7864079 ER PT J AU MORAN, A DAVIS, VH TURNER, RJ AF MORAN, A DAVIS, VH TURNER, RJ TI NA+ CHANNELS IN MEMBRANE-VESICLES FROM INTRALOBULAR SALIVARY DUCTS SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE SODIUM CONDUCTANCE; SALT REABSORPTION; AMILORIDE; GRANULAR DUCTS ID SUBMANDIBULAR GRANULAR DUCTS; MOUSE MANDIBULAR GLANDS; AMILORIDE ANALOGS; ION-TRANSPORT; BLADDER; FLUXES; CELLS; CA2+ AB Electrical potential-driven Na-22(+) fluxes were measured in membrane vesicles prepared from male and female rat submandibular intralobular ducts. A relatively temperature-independent (Q(10) = 1.45 +/- 0.15), amiloride-inhibitable (mean affinity constant approximate to 1 mu M), rheogenic Na+ transport pathway was observed. The relative potency of amiloride analogues for inhibition of this pathway was amiloride > ethylisopropylamiloride > phenamil, similar to that of the ''low-amiloride-affinity'' Na+ channel recently observed in a number of other tissues. These results are consistent with the existence of the apical Na+ channel thought to be involved in intralobular ductal salt reabsorption. No significant difference was found in the magnitude or pharmacology of electrogenic Na+ fluxes in vesicles prepared from male and female rat intralobular ducts, suggesting that the sexual dimorphism observed in this tissue is not reflected at the level of the apical membrane Na+ channel. Amiloride-sensitive Na-22(+) fluxes in intralobular ductal membranes were of the same magnitude as Na-22(+) fluxes measured in similarly prepared and assayed vesicles from the toad bladder, a tissue thought to be a rich source of amiloride-sensitive Na+ channels. C1 NIDR, CLIN INVEST & PATIENT CARE BRANCH, BETHESDA, MD 20892 USA. BEN GURION UNIV NEGEV, FAC HLTH SCI, DEPT PHYSIOL, BEER SHEVA, ISRAEL. RI MORAN, ARIE/F-1210-2012 NR 30 TC 10 Z9 10 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 EI 1522-1563 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD FEB PY 1995 VL 268 IS 2 BP C350 EP C355 PG 6 WC Cell Biology; Physiology SC Cell Biology; Physiology GA QF550 UT WOS:A1995QF55000010 PM 7864074 ER PT J AU SMITH, TJ WANG, HS EVANS, CH AF SMITH, TJ WANG, HS EVANS, CH TI LEUKOREGULIN IS A POTENT INDUCER OF HYALURONAN SYNTHESIS IN CULTURED HUMAN ORBITAL FIBROBLASTS SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE GRAVES DISEASE; INFLAMMATION; OPHTHALMOPATHY; CYTOKINE; GLUCOCORTICOID ID HUMAN DERMAL FIBROBLASTS; HUMAN-SKIN FIBROBLASTS; CELL-DERIVED CYTOKINE; INTERFERON-GAMMA; GLYCOSAMINOGLYCAN SYNTHESIS; GENE-EXPRESSION; GRAVES OPHTHALMOPATHY; PROTEIN-SYNTHESIS; THYROID-HORMONE; ACCUMULATION AB Leukoregulin, a 50-kDa glycoprotein lymphokine, can regulate the extracellular matrix in dermal fibroblasts. Here we investigate the effects of leukoregulin on the synthesis of glycosaminoglycans in human orbital fibroblasts. We demonstrate that leukoregulin enhances the incorporation of [H-3]glucosamine into glycosaminoglycans. The effect is dose dependent in the concentration range tested (0.1-2 U/ml), is maximal at 1 U/ml, and is time dependent. [H-3]glycosaminoglycan accumulation is enhanced 7.67 +/- 1.23-fold (SE, n = 7) in orbital fibroblast strains. Pulse-chase studies indicate that this enhanced accumulation is not a result of a decreased rate of macromolecular degradation. Radiolabeled material induced by leukoregulin is sensitive to Streptomyces hyaluronidase digestion. Dexamethasone (10(-8) M) and cycloheximide (10 mu g/ml) can block the cytokine's stimulation of hyaluronan synthesis. [S-35]sulfate incorporation into glycosaminoglycan is unaffected by leukoregulin. In dermal fibroblasts, leukoregulin increased hyaluronan synthesis 3.66 +/- 0.37-fold (n = 5 strains, P < 0.02 compared with orbit). The increase in hyaluronan synthesis in orbital fibroblasts is substantially greater than that observed previously with other cytokines, making leukoregulin a candidate molecular trigger in Graves' ophthalmopathy. C1 VET AFFAIRS MED CTR, ALBANY MED COLL, DEPT MOLEC BIOL, DIV MOLEC & CELLULAR MED, ALBANY, NY 12208 USA. NCI, DIV CANC ETIOL, BIOL LAB, TUMOR BIOL SECT, BETHESDA, MD 20892 USA. RP SMITH, TJ (reprint author), VET AFFAIRS MED CTR, ALBANY MED COLL, DEPT MED & BIOCHEM, DIV MOLEC & CELLULAR MED, A-175, ALBANY, NY 12208 USA. FU NEI NIH HHS [R01 EY-08976] NR 33 TC 76 Z9 77 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 FEB PY 1995 VL 268 IS 2 BP C382 EP C388 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA QF550 UT WOS:A1995QF55000014 PM 7864077 ER PT J AU BOSCHERO, AC SZPAKGLASMAN, M CARNEIRO, EM BORDIN, S PAUL, I ROJAS, E ATWATER, I AF BOSCHERO, AC SZPAKGLASMAN, M CARNEIRO, EM BORDIN, S PAUL, I ROJAS, E ATWATER, I TI OXOTREMORINE-M POTENTIATION OF GLUCOSE-INDUCED INSULIN RELEASE FROM RAT ISLETS INVOLVES M(3) MUSCARINIC RECEPTORS SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE CHOLINERGIC RECEPTORS; INSULIN SECRETION; PANCREATIC; BETA-CELLS; CALCIUM; POTASSIUM ID PANCREATIC BETA-CELLS; MOUSE ISLETS; B-CELLS; ACETYLCHOLINE; SECRETION; MODULATION; CA-2+; MOBILIZATION; STIMULATION; ACTIVATION AB cDNAs encoding for M(1) and M(3) muscarinic acetylcholine (ACh) receptors were detected in rat pancreatic islet cells by polymerase chain reaction (PCR) amplification techniques. A new cholinergic agonist, oxotremorine-m (oxo-m), in the presence of glucose (5.6 mM), produced a dose-dependent potentiation of insulin secretion saturating at similar to 5 mu M. This effect was suppressed by the L-type Ca2+ channel blocker nifedipine. Higher doses of oxo-m (50 mu M) induced a biphasic insulin response both at low (5.6 mM) or high (16.7 mM) glucose concentrations. In a Ca2+-deficient medium containing glucose (5.6 mM), oxo-m evoked only a reduced first phase of insulin secretion. The potentiating effects of oxo-m were inhibited by the muscarinic receptor antagonists 4-diphenylacetoxy-N-methylpiperidine methiodide (M(3)), hexahydro-sila-difenidol hydrochloride, p-fluoro analogue (M(3)>M(1)>M(2)), and pirenzepine (M(1)) in a dose-dependent manner; half-maximal inhibitory concentration values were similar to 5, 20, and 340 nM, respectively. The PCR results demonstrate the presence of M(1) and M(3) muscarinic ACh receptors in the islet tissue, and the secretion data strongly suggest that the potentiation of glucose-induced insulin release evoked by oxo-m depends on the activation of a muscarinic M(3)-subtype receptor present in the beta-cell membrane. C1 NIDDKD, CELL BIOL & GENET LAB, BETHESDA, MD 20892 USA. NIDDKD, NEUROSCI LAB, BETHESDA, MD 20892 USA. RI Carneiro, Everardo /D-4758-2012; Boschero, Antonio/O-7525-2014 OI Boschero, Antonio/0000-0003-3829-8570 NR 32 TC 88 Z9 88 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD FEB PY 1995 VL 268 IS 2 BP E336 EP E342 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA QF545 UT WOS:A1995QF54500020 PM 7864111 ER PT J AU BERGASA, NV SABOL, SL YOUNG, WS KLEINER, DE JONES, EA AF BERGASA, NV SABOL, SL YOUNG, WS KLEINER, DE JONES, EA TI CHOLESTASIS IS ASSOCIATED WITH PREPROENKEPHALIN MESSENGER-RNA EXPRESSION IN THE ADULT-RAT LIVER SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE HEPATIC OPIOIDS; BILIARY CIRRHOSIS; BILE DUCT RESECTION; METHIONINE-ENKEPHALIN ID MESSENGER-RNA; NALMEFENE THERAPY; RIBONUCLEIC-ACID; CONTROLLED TRIAL; PRURITUS; GENE; ENKEPHALIN; PRECURSOR; SEQUENCE; CLONING AB Cholestatic liver disease is associated with clinical and experimental findings consistent with increased opioidergic neuromodulation, increased plasma total opioid activity, and elevated plasma enkephalin concentrations. In contrast to the normal adult rat liver, preproenkephalin mRNA was detected by Northern blotting in livers of adult rats with cholestasis due to bile duct resection and not in the sham-resected controls. Preprodynorphin mRNA was not detected in livers of either group, while preproopiomelanocortin mRNA was found in very low levels in both groups. Preproenkephalin mRNA was not expressed in the livers of rats with acute hepatocellular necrosis induced by thioacetamide. Hybridization histochemistry of cholestatic livers demonstrated the presence of preproenkephalin mRNA primarily over cells in the periportal areas, some of which appeared to be proliferating bile ductular cells. Immunohistochemical staining of cholestatic liver indicated the production of at least Met-enkephalin in association with preproenkephalin gene expression. These findings suggest that the liver itself, by synthesizing enkephalins, contributes directly to the abnormalities of the opioid system reported in cholestasis. C1 NIDDKD, DIGEST DIS BRANCH, LIVER DIS SECT, BETHESDA, MD 20892 USA. NHLBI, BIOCHEM GENET LAB, BETHESDA, MD 20892 USA. NIMH, CELL BIOL LAB, BETHESDA, MD 20892 USA. NCI, PATHOL LAB, BETHESDA, MD 20892 USA. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 NR 37 TC 35 Z9 36 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD FEB PY 1995 VL 268 IS 2 BP G346 EP G354 PG 9 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA QF544 UT WOS:A1995QF54400019 PM 7864131 ER PT J AU JANCZEWSKI, AM SPURGEON, HA STERN, MD LAKATTA, EG AF JANCZEWSKI, AM SPURGEON, HA STERN, MD LAKATTA, EG TI EFFECTS OF SARCOPLASMIC-RETICULUM CA2+ LOAD ON THE GAIN FUNCTION OF CA2+ RELEASE BY CA2+ CURRENT IN CARDIAC-CELLS SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Note DE EXCITATION-CONTRACTION COUPLING; CYTOSOLIC CALCIUM; INDO 1; CAFFEINE; RAT VENTRICULAR MYOCYTES ID PURKINJE-CELL; CALCIUM; CONTRACTION; RAT; INACTIVATION; MUSCLE; TRANSIENTS; DEPENDENCE; MYOCYTES; CHANNELS AB We studied the effects of variable sarcoplasmic reticulum (SR) Ca2+ loading on changes in the gain index of Ca2+ release from the SR, measured as the ratio of the amount of Ca2+ released to the magnitude of the Ca2+ current (I-Ca) integrated for the initial 20 ms of the depolarization, in whole cell voltage-clamped rat ventricular myocytes dialyzed with the Ca2+ indicator indo 1 salt at 23 degrees C. Changes in I-Ca were measured directly, and changes in the SR Ca2+ release were indexed by changes in the amplitudes and rates of rise of cytosolic Ca2+ (Ca-i(2+)) transients. The SR Ca2+ load was graded by the duration of conditioning voltage-clamp steps and verified by caffeine-dependent Ca-i(2+) transients. A train of abbreviated (from 100 to 20 ms) voltage-clamp depolarizations, which triggers SR Ca2+ release but fails to replenish the SR with Ca2+, diminished the SR Ca2+ load by 56 +/- 5%, did not alter peak I-Ca but reduced the amplitudes of the I-Ca-dependent Ca-i(2+) transients by 52 +/- 3%, and decreased the gain index by 60 i 3% (SE; n = 5 or 6). Changes in the amplitudes of Ca-i(2+) transients elicited by I-Ca and changes in the gain index were Linearly correlated (r(2) = 0.83 and 0.79, respectively; P < 0.001 for each) with changes in amplitudes of Ca-i(2+) transients elicited by caffeine pulses applied in lieu of the respective voltage-clamp pulses. The linear dependence of gain on SR Ca2+ loading provides further evidence against the existence of strong positive feedback of released Ca2+ on the Ca2+ release triggering mechanism and has theoretical implications for force-interval and staircase phenomena in the heart. C1 NIA, CTR GERONTOL RES, CARDIOVASC SCI LAB, BALTIMORE, MD 21224 USA. NR 15 TC 84 Z9 84 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD FEB PY 1995 VL 268 IS 2 BP H916 EP H920 PG 5 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA QF814 UT WOS:A1995QF81400050 PM 7864219 ER PT J AU KARZAI, W REILLY, JM HOFFMAN, WD CUNNION, RE DANNER, RL BANKS, SM PARRILLO, JE NATANSON, C AF KARZAI, W REILLY, JM HOFFMAN, WD CUNNION, RE DANNER, RL BANKS, SM PARRILLO, JE NATANSON, C TI HEMODYNAMIC-EFFECTS OF DOPAMINE, NOREPINEPHRINE, AND FLUIDS IN A DOG-MODEL OF SEPSIS SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE CATECHOLAMINES; RESUSCITATION; VENTRICULAR PERFORMANCE; SEPTIC SHOCK ID HUMAN SEPTIC SHOCK; CANINE MODEL; ESCHERICHIA-COLI; CARDIOVASCULAR DYSFUNCTION; ENDOTOXIN-SHOCK; BLOOD-FLOW; THERAPY; PERFORMANCE; CHALLENGES; MECHANISMS AB To study how sepsis affects hemodynamic responses to catecholamines and fluids, either Escherichia coli-infected (septic, n = 8) or sterile (controls, n = 6) fibrin clots were implanted intraperitoneally into 2-yr-old beagles. Hemodynamics were measured at each of four doses of dopamine (0, 5, 10, and 20 mu g.kg(-1).min(-1)) and norepinephrine (0, 10, 20, and 40 mu g.min(-1)), before and after infusion of fluid (Ringer 40 ml.kg(-1)). Septic animals had lower mean arterial pressure (MAP, P = 0.04), stroke volume index (SVI, P = 0.0001), and left ventricular (LV) ejection fraction (LVEF) (P = 0.0001) than controls. During this time, increasing doses of dopamine and norepinephrine produced corresponding increases (P < 0.001) in LVEF, SVI, and MAP. However, during sepsis, the ability of dopamine to increase MAP diminished, while its ability to increase LVEF and SVI was maintained. Conversely, the ability of norepinephrine to increase LVEF and SVI diminshed, but its ability to increase MAP was maintained. During sepsis, fluids alone increased (P < 0.05) MAP, LVEF, SVI, and cardiac index (CI). Fluids with catecholamines also significantly increased (P < 0.05) MAP with only minimal increases in LVEF, SVI, and CI. These data demonstrate that during sepsis without catecholamines, fluids improve cardiac performance and systemic pressures, but with catecholamines, fluids have minimal effects on cardiac performance and augment MAP. Furthermore, during sepsis dopamine is more effective than norepinephrine in increasing LV performance, but norepinephrine is more effective than dopamine in increasing systemic pressures. C1 NIH, WARREN GRANT MAGNUSON CLIN CTR, DEPT CRIT CARE MED, BETHESDA, MD 20892 USA. ARMED FORCES RADIOBIOL RES INST, DEF NUCL AGCY, BETHESDA, MD 20814 USA. NR 39 TC 17 Z9 17 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 FEB PY 1995 VL 268 IS 2 BP H692 EP H702 PG 11 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA QF814 UT WOS:A1995QF81400024 PM 7864196 ER PT J AU FRERICHS, KU DIENEL, GA CRUZ, NF SOKOLOFF, L HALLENBECK, JM AF FRERICHS, KU DIENEL, GA CRUZ, NF SOKOLOFF, L HALLENBECK, JM TI RATES OF GLUCOSE-UTILIZATION IN BRAIN OF ACTIVE AND HIBERNATING GROUND-SQUIRRELS SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE HIBERNATION; CEREBRAL ISCHEMIA; DEOXYGLUCOSE; ENERGY METABOLISM ID 2-DEOXYGLUCOSE UPTAKE; DEOXYGLUCOSE METHOD; LUMPED CONSTANT; BLOOD-FLOW; METABOLISM; PHOSPHORYLATION; STABILITY; GLYCOGEN; AROUSAL; NUCLEUS AB Rates of glucose utilization (CMR(Glc)) were determined in some cerebral structures of active warm- and cold-adapted ground squirrels and hibernating ground squirrels with [C-14]deoxyglucose (DG) by direct chemical measurement of precursor and products in samples dissected from funnel-frozen brain. The rate of supply relative to demand of glucose and [C-14]DG in brain of hibernating animals was similar to or greater than that of controls. [C-14]DG cleared from the plasma in hibernators much more slowly than in active animals, and the level of unmetabolized [C-14]DG in brain and the integrated specific activity of the precursor pool in plasma exceeded those of the active animals by 4- to 10-fold. At 45 min after an intravenous pulse of [C-14]DG, the unmetabolized [C-14]DG remaining in the brains of the hibernators accounted for similar to 96% of the total C-14 compared with similar to 10-15% in the active animals. The value of lambda, a factor contained in the lumped constant of the operational equation of the [C-14]DG method, was estimated for each animal and found to be relatively constant over the sixfold range of glucose levels in the brains of all animals. Calculated CMR(Glc) in squirrels in deep hibernation was only 1-2% of the values in active animals. C1 NIMH, CEREBRAL METAB LAB, BETHESDA, MD 20892 USA. NINCDS, STROKE BRANCH, BETHESDA, MD 20892 USA. NR 38 TC 26 Z9 27 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regulat. Integr. Compar. Physiol. PD FEB PY 1995 VL 268 IS 2 BP R445 EP R453 PG 9 WC Physiology SC Physiology GA QF753 UT WOS:A1995QF75300019 PM 7864240 ER PT J AU SUN, Y DEIBLER, GE JEHLE, J MACEDONIA, J DUMONT, I DANG, T SMITH, CB AF SUN, Y DEIBLER, GE JEHLE, J MACEDONIA, J DUMONT, I DANG, T SMITH, CB TI RATES OF LOCAL CEREBRAL PROTEIN-SYNTHESIS IN THE RAT DURING NORMAL POSTNATAL-DEVELOPMENT SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE LEUCINE; LEUCINE RECYCLING; BRAIN; PROTEIN DEGRADATION ID PRECURSOR POOL; SUPERIOR COLLICULUS; ADULT-RATS; BRAIN; DEGRADATION; NEUROPHYSIN; VASOPRESSIN; MATURATION; NUCLEUS; INVIVO AB The degree of recycling of leucine derived from protein breakdown into the precursor pool for protein synthesis was measured in rat brain at different postnatal ages, and age-specific values were used in the calculation of regional (local) rates of cerebral leucine incorporation into protein (lCPS(leu)) in 44 brain regions and the brain as a whole. Early in development, a greater fraction of the precursor leucine pool is derived from protein breakdown, indicating that protein degradation is higher in young rats compared with adults. In whole brain and in most regions, values for lCPS(leu) were highest at 10 days and gradually decreased with age. By 60 days of age, values in cortex were similar to 60% of those at 10 days of age. In the paraventricular and supraoptic nuclei of the hypothalamus, however, lCPS(leu) increased during development, reaching peak values in adults. In white matter of the cerebellum and the cerebrum, peaks of lCPS(leu) were reached at 14 and 21 days, respectively, approximately at the times of maximum rates of myelination. C1 NIMH, CEREBRAL METAB LAB, BETHESDA, MD 20892 USA. NR 33 TC 24 Z9 24 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regulat. Integr. Compar. Physiol. PD FEB PY 1995 VL 268 IS 2 BP R549 EP R561 PG 13 WC Physiology SC Physiology GA QF753 UT WOS:A1995QF75300032 PM 7864252 ER PT J AU LYNN, WR FREEDMAN, LS GREEN, SB CORLE, DK GAIL, M GLASGOW, RE HARTWELL, TD CUMMINGS, KM OCKENE, JK GIFFEN, CA AF LYNN, WR FREEDMAN, LS GREEN, SB CORLE, DK GAIL, M GLASGOW, RE HARTWELL, TD CUMMINGS, KM OCKENE, JK GIFFEN, CA TI COMMUNITY INTERVENTION TRIAL FOR SMOKING CESSATION (COMMIT) .1. COHORT RESULTS FROM A 4-YEAR COMMUNITY INTERVENTION SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID STANFORD 5-CITY PROJECT; CARDIOVASCULAR-DISEASE; CIGARETTE-SMOKING; EDUCATION; PREVALENCE; CAMPAIGN; QUIT AB Objectives. The primary hypothesis of COMMIT (Community Intervention Trial for Smoking Cessation) was that a community-level, multichannel, 4-year intervention would increase quit rates among cigarette smokers, with heavy smokers (greater than or equal to 25 cigarettes per day) of priority. Methods. One community within each of 11 matched community pairs (10 in the United States, 1 in Canada) was randomly assigned to intervention. Endpoint cohorts totaling 10 019 heavy smokers and 10 328 light-to-moderate smokers were followed by telephoner Results. The mean heavy smoker quit rate (i.e., the fraction of cohort members who had achieved and maintained cessation at the end of the trial)was 0.180 for intervention communities versus 0.187 for comparison communities, a nonsignificant difference (one-sided P = .68 by permutation test; 90% test-based confidence interval (CI) for the difference = -0.031, 0.019). For light-to-moderate smokers, corresponding quit rates were 0.306 and 0.275; this difference was significant (P = .004; 90% CI = 0.014, 0.047). Smokers in intervention communities had greater perceived exposure to smoking control activities, which correlated with outcome only for light-to-moderate smokers. Conclusions. The impact of this community-based intervention on light-to-moderate smokers, although modest, has public health importance. This intervention did not increase quit rates of heavy smokers; reaching them may require new clinical programs and policy changes. RP LYNN, WR (reprint author), NCI,EXECUT PLAZA N,SUITE 241,BETHESDA,MD 20892, USA. NR 34 TC 246 Z9 249 U1 0 U2 4 PU AMER PUBLIC HEALTH ASSN 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 FEB PY 1995 VL 85 IS 2 BP 183 EP 192 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QH011 UT WOS:A1995QH01100010 ER PT J AU LYNN, WR FREEDMAN, LS GREEN, SB CORLE, DK GAIL, M LICHTENSTEIN, E HARTWELL, TD CUMMINGS, KM OCKENE, JK HYMOWITZ, N GIFFEN, CA AF LYNN, WR FREEDMAN, LS GREEN, SB CORLE, DK GAIL, M LICHTENSTEIN, E HARTWELL, TD CUMMINGS, KM OCKENE, JK HYMOWITZ, N GIFFEN, CA TI COMMUNITY INTERVENTION TRIAL FOR SMOKING CESSATION (COMMIT) .2. CHANGES IN ADULT CIGARETTE-SMOKING PREVALENCE SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID STANFORD 5-CITY PROJECT; NORTH-KARELIA-PROJECT; RISK-FACTORS; CARDIOVASCULAR-DISEASE; PREVENTION; EDUCATION; PROGRAM AB Objectives. COMMIT (Community Intervention Trial for Smoking Cessation) investigated whether a community-level multichannel intervention would decrease the prevalence of adult cigarette smoking and increase quitting, with heavy smokers (greater than or equal to 25 cigarettes per day) receiving the highest priority. Methods. One community within each of 11 matched community pairs (10 in the United States, 1 in Canada) was randomly assigned to intervention. Baseline (1988) and final(1993) telephone surveys sampled households to determine prevalence of smoking behavior. Results. Among the target population aged 25 to 64 years, there was no intervention effect on heavy smoking prevalence, which decreased by 2.9 percentage points in both intervention and comparison communities. Overall smoking prevalence decreased by 3.5 in intervention communities vs 3.2 in comparison communities, a difference not statistically significant, while the mean quit ratios were 0.198 versus 0.185, respectively, a difference of 0.013 (90% test-based confidence interval = -0.003, 0.028). Conclusions. Results are consistent with the cohort analysis reported separately, although the more powerful cohort design showed a statistically significant intervention effect upon light-to-moderate smokers. This community-based intervention did not have a significant impact On smoking prevalence beyond the favorable secular trends. In future efforts, additional strategies should be incorporated and rigorously evaluated. RP LYNN, WR (reprint author), NCI,EXECUT PLAZA N,SUITE 241,BETHESDA,MD 20892, USA. NR 37 TC 121 Z9 124 U1 0 U2 4 PU AMER PUBLIC HEALTH ASSN 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 FEB PY 1995 VL 85 IS 2 BP 193 EP 200 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QH011 UT WOS:A1995QH01100011 ER PT J AU SERDULA, MK COATES, RJ BYERS, T SIMOES, E MOKDAD, AH SUBAR, AF AF SERDULA, MK COATES, RJ BYERS, T SIMOES, E MOKDAD, AH SUBAR, AF TI FRUIT AND VEGETABLE INTAKE AMONG ADULTS IN 16 STATES - RESULTS OF A BRIEF TELEPHONE SURVEY SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Note ID CONSUMPTION; DIET AB A brief food frequency questionnaire was used to assess daily fruit and vegetable consumption among 23 699 adults in 16 US states sampled in a random-digit dialing telephone survey. Men consumed fewer servings per day (3.3) than did women (3.7). Only 20% of the population consumed the recommended 5 or more daily servings. Intakes varied somewhat by state and were lower among the young and the less educated. Efforts are needed to improve fruit and vegetable consumption among all Americans, especially younger adults and those with lower levels of education. C1 EMORY UNIV,SCH PUBL HLTH,DIV EPIDEMIOL,ATLANTA,GA. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. RP SERDULA, MK (reprint author), CTR DIS CONTROL & PREVENT,NCCDPHP K26,DIV NUTR,4770 BUFORD HWY NE,ATLANTA,GA 30341, USA. OI Simoes, Eduardo/0000-0003-4371-4305 NR 19 TC 102 Z9 102 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSN 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 FEB PY 1995 VL 85 IS 2 BP 236 EP 239 DI 10.2105/AJPH.85.2.236 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QH011 UT WOS:A1995QH01100017 PM 7856784 ER PT J AU TOCKMAN, MS PEARSON, JD FLEG, JL METTER, EJ KAO, SY RAMPAL, KG CRUISE, LJ FOZARD, JL AF TOCKMAN, MS PEARSON, JD FLEG, JL METTER, EJ KAO, SY RAMPAL, KG CRUISE, LJ FOZARD, JL TI RAPID DECLINE IN FEV(1) - A NEW RISK FACTOR FOR CORONARY HEART-DISEASE MORTALITY SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article AB Coronary heart disease (CHD) is the leading cause of mortality in the United States. The present cohort study was conducted to determine whether rate of FEV(1) loss independently predicts CHD mortality in apparently healthy men. White male Baltimore Longitudinal Study of Aging (BLSA) participants without CHD underwent clinical evaluation at 2-yr intervals; 883 had satisfactory pulmonary and lipid studies and returned for a least one visit. Cases were BLSA subjects without CHD on entry who died a ''coronary death'' (death from acute myocardial infarction, sudden death, or congestive heart failure in the presence of coronary artery disease). Forced expiratory maneuvers followed American Thoracic Society guidelines. Serum cholesterol, blood pressure, cigarette smoking, and body mass index were obtained from the BLSA database. There were 79 CHD deaths and 804 survivors during an average follow-up of 17.4 yr. After adjustment for age, initial FEV(1)% predicted, smoking status, hypertension, and cholesterol, a time-dependent proportional hazards model showed that cardiac mortality, but not all causes of mortality, generally increased with increasing quintile of FEV(1) decline for the entire cohort (relative risk [RR] 2.92-5.13) and separately for the subset of never-smokers. Thus, excess CHD mortality follows a large decline in FEV(1), independent of the initial FEV(1)% predicted, cigarette smoking, and other common CHD risk factors. C1 NIA, GERONTOL RES CTR, BALTIMORE, MD 21224 USA. UNIV KEBANGSAAN MALAYSIA, FAC MED, DEPT COMMUNITY HLTH, KUALA LUMPUR, MALAYSIA. RP TOCKMAN, MS (reprint author), JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, DEPT ENVIRONM HLTH SCI, 615 N WOLFE ST, ROOM 7515, BALTIMORE, MD 21205 USA. RI Fozard, James Leonard/B-3660-2009 NR 31 TC 101 Z9 105 U1 0 U2 4 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD FEB PY 1995 VL 151 IS 2 BP 390 EP 398 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA QF547 UT WOS:A1995QF54700025 PM 7842197 ER PT J AU LASKY, JA COIN, PG LINDROOS, PM OSTROWSKI, LE BRODY, AR BONNER, JC AF LASKY, JA COIN, PG LINDROOS, PM OSTROWSKI, LE BRODY, AR BONNER, JC TI CHRYSOTILE ASBESTOS STIMULATES PLATELET-DERIVED GROWTH FACTOR-AA PRODUCTION BY RAT LUNG FIBROBLASTS IN-VITRO - EVIDENCE FOR AN AUTOCRINE LOOP SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID SMOOTH-MUSCLE CELLS; FACTOR-BB ISOFORMS; ALVEOLAR MACROPHAGES; UP-REGULATION; GENE-EXPRESSION; ALPHA-RECEPTOR; FACTOR-AB; PDGF-AA; PROLIFERATION; EXPOSURE AB We have investigated the mitogenic and chemotactic role of platelet-derived growth factor (PDGF) in pulmonary fibrogenesis induced by chrysotile asbestos. Since fibroblasts phagocytize asbestos in the lung interstitium, we have sought to learn whether the fibers alter the production of PDGF-like molecules by rat lung fibroblasts or induce mitogenesis of these fibroblasts in vitro. Conditioned medium as well as cell lysates from fibroblasts exposed to asbestos contained approximately 4-fold more PDGF than unexposed cells as detected by Western blot. Two distinct molecular weight forms of PDGF (36 and 18 kD) were detected by Western blotting. We postulate that these PDGF-like molecules are homologues of human PDGF-AA since we could not detect any PDGF in a sensitive enzyme immunoassay that recognized only PDGF-BB and PDGF-AB. Furthermore, PDGF-A chain mRNA was readily detected by Northern analysis, whereas PDGF-B chain mRNA was not detected by conventional Northern analysis. However, message amplification using a reverse transcriptase polymerase chain reaction allowed detection of the B-chain message. A significant dose-dependent mitogenic effect of asbestos was found by using both a cell proliferation assay and nuclear labeling with bromodeoxyuridine when fibroblasts were exposed under serum-free conditions. This mitogenesis induced directly by asbestos was blocked almost entirely with an anti-PDGF antibody that neutralized all three PDGF isoforms. Thus, these data support our hypothesis that an autocrine loop for PDGF-AA is operative in vitro following exposure to asbestos in lung fibroblasts, and we suggest that this signaling pathway could be significant in the pathogenesis of pulmonary fibrosis. C1 NIEHS,PULM PATHOBIOL LAB,RES TRIANGLE PK,NC 27709. DUKE UNIV,MED CTR,DIV PULM ALLERGY & CRIT CARE MED,DURHAM,NC. FU NHLBI NIH HHS [5T32HL07538-09] NR 28 TC 41 Z9 42 U1 0 U2 0 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 FEB PY 1995 VL 12 IS 2 BP 162 EP 170 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA QF749 UT WOS:A1995QF74900008 PM 7865215 ER PT J AU LEVINE, SJ LARIVEE, P LOGUN, C ANGUS, CW OGNIBENE, FP SHELHAMER, JH AF LEVINE, SJ LARIVEE, P LOGUN, C ANGUS, CW OGNIBENE, FP SHELHAMER, JH TI TUMOR-NECROSIS-FACTOR-ALPHA INDUCES MUCIN HYPERSECRETION AND MUC-2 GENE-EXPRESSION BY HUMAN AIRWAY EPITHELIAL-CELLS SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID ALVEOLAR MACROPHAGES; CYTOKINES; SECRETION; ASTHMA; INTERLEUKIN-6; SEQUENCES; RELEASE; LUNG; STIMULATION; INDUCTION AB Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional, proinflammatory cytokine that is capable of activating a diverse number of target genes within multiple cell types. Little information is known regarding the role of TNF-alpha in the regulation of human airway mucin hypersecretion and MUG-2 gene expression. To assess the effect of TNF-alpha exposure on mucin secretion, human airway organ cultures and primary cultures of human airway epithelial cells were stimulated with 20 ng/ml of recombinant human TNF-alpha and mucin secretion quantitated by an enzyme-linked immunosorbent assay using a specific monoclonal antibody directed against human airway mucin. Significant increases in mucin secretion from human airway organ cultures were initially detected at 1 h, peaked at 8 h, and persisted for 24 h. The TNF-alpha-mediated mucin hypersecretion at 8 h was concentration dependent. Significant increases in mucin secretion from primary cultures of human airway epithelial cells were initially detected at 4 h, peaked at 48 h, and persisted for 72 h after stimulation with 20 ng/ml of recombinant human TNF-alpha. The TNF-alpha-mediated mucin hypersecretion at 48 h from primary cultures of human airway epithelial cells was inhibited by coincubation with soluble 55 kD, type I TNF receptors. Using reverse transcription-polymerase chain reaction and a human pulmonary mucoepidermoid carcinoma cell line (NCI-H292), increases in MUG-2 steady-state mRNA levels were first detectable after 30 min of TNF-alpha stimulation and persisted for 24 h. Cycloheximide did not inhibit TNF-alpha-mediated MUG-2 mRNA expression at 1 h, suggesting that new protein translation was not required. In addition, TNF-alpha-mediated MUG-2 gene expression was inhibited by calphostin C and genistein, suggesting that signal transduction was dependent on both protein kinase C and tyrosine kinases. These data suggest that human airway epithelial cell mucin hypersecretion and MUC-2 gene expression may be regulated by proinflammatory cytokines, such as TNF-alpha. Consequently, TNF-alpha-mediated mucin hypersecretion and MUG-2 gene expression might contribute to the pathogenesis of human inflammatory airway disorders, such as asthma. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BETHESDA,MD 20892. NR 50 TC 165 Z9 167 U1 0 U2 5 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 FEB PY 1995 VL 12 IS 2 BP 196 EP 204 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA QF749 UT WOS:A1995QF74900012 PM 7865217 ER PT J AU BARKSDALE, SK HALLAHAN, CW KERR, GS FAUCI, AS STERN, JB TRAVIS, WD AF BARKSDALE, SK HALLAHAN, CW KERR, GS FAUCI, AS STERN, JB TRAVIS, WD TI CUTANEOUS PATHOLOGY IN WEGENERS GRANULOMATOSIS - A CLINICOPATHOLOGICAL STUDY OF 75 BIOPSIES IN 46 PATIENTS SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE LEUKOCYTOCLASTIC VASCULITIS; WEGENERS GRANULOMATOSIS; GRANULOMATOUS INFLAMMATION; SKIN ID VASCULITIS; DISEASE AB While no cutaneous lesion is specific for Wegener's granulomatosis (WG), several histopathologic entities, including leukocytoclastic vasculitis and necrotizing granulomatous inflammation, are characteristic. This report details the histopathologic features of 75 cutaneous biopsies from 46 patients with WG. Biopsies were subdivided into histologic groups that included leukocytoclastic vasculitis (31%), granulomatous inflammation (GI) (19%), nonspecific ulceration (4%), superficial dermal and epidermal necrosis without inflammation (2.7%), erythema nodosum (2.7%), granuloma annulare (1%), chronic inflammation (31%), and acute inflammatory lesions without vasculitis (9%). No convincing example of granulomatous vasculitis was observed. The histopathologic subgroups were correlated with clinical features, and the results were compared with those from a control group of 82 WG patients with no skin involvement, We found that the histopathologic subgroups of leukocytoclastic vasculitis and granulomatous inflammation correlated with different clinical courses. Patients with leukocytoclastic vasculitis developed WG at an earlier age (median age, 30 years) than did the control group (median age, 45 years). Leukocytoclastic vasculitis developed shortly after onset of WG (median, 15 months vs. 35 months for patients with nonspecific chronic inflammation). All lesions occurred during active disease. Active disease with leukocytoclastic vasculitis was associated with a mean erythrocyte sedimentation rate twice that of active disease in the same patient when leukocytoclastic vasculitis was absent. The patients with leukocytoclastic vasculitis had more rapidly progressive and widespread WG than patients with granulomatous skin lesions or patients without skin lesions. A marked excess of joint and musculoskeletal symptoms and renal disease was seen in patients with leukocytoclastic vasculitis. Patients with granulomatous inflammation also developed WG at an early age (median age, 30 years) when compared with the control group. Cutaneous granulomatous lesions also developed shortly after presentation (median, 12 months). Only 64% of granulomatous biopsies were from patients with active disease. These patients frequently had neither renal nor pulmonary manifestations of WG, and their disease progressed at a slower rate than that of the patients with leukocytoclastic vasculitis. These findings suggest that the cutaneous lesions characteristic of WG may correlate with the activity, distribution, and course of the disease. C1 NCI, PATHOL LAB, BETHESDA, MD 20892 USA. NIAID, IMMUNOREGULAT LAB, BETHESDA, MD 20892 USA. ARMED FORCES INST PATHOL, DEPT PULM & MEDIASTINAL PATHOL, WASHINGTON, DC 20306 USA. RP NCI, TUMOR VIRUS BIOL LAB, BLDG 41, ROOM C111, BETHESDA, MD 20892 USA. NR 23 TC 64 Z9 68 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD FEB PY 1995 VL 19 IS 2 BP 161 EP 172 DI 10.1097/00000478-199502000-00005 PG 12 WC Pathology; Surgery SC Pathology; Surgery GA QC789 UT WOS:A1995QC78900005 PM 7832276 ER PT J AU SHARP, TW THORNTON, SA WALLACE, MR DEFRAITES, RE SANCHEZ, JL BATCHELOR, RA ROZMAJZL, PJ HANSON, RK ECHEVERRIA, P KAPIKIAN, AZ XIANG, XJ ESTES, MK BURANS, JP AF SHARP, TW THORNTON, SA WALLACE, MR DEFRAITES, RE SANCHEZ, JL BATCHELOR, RA ROZMAJZL, PJ HANSON, RK ECHEVERRIA, P KAPIKIAN, AZ XIANG, XJ ESTES, MK BURANS, JP TI DIARRHEAL-DISEASE AMONG MILITARY-PERSONNEL DURING OPERATION-RESTORE-HOPE, SOMALIA, 1992-1993 SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID HOUSEFLIES MUSCA-DOMESTICA; TRAVELERS DIARRHEA; DESERT-SHIELD; SHIGELLOSIS; TRANSMISSION; PATHOGENS; STORM; TRIAL AB The potential for widespread diarrheal disease was regarded as a substantial threat to U.S. troops participating in the early phases of Operation Restore Hope in Somalia. Outpatient surveillance of 20,859 U.S. troops deployed during the first eight weeks, however, indicated that a mean of only 0.8% (range 0.5-1.2%) of personnel sought care for diarrhea each week, and in three epidemiologic surveys, < 3% of troops reported experiencing a diarrheal illness per week. Despite these low overall attack rates, diarrhea accounted for 16% of 381 hospital admissions and 20% of 245 patients admitted with a temperature greater than or equal to 38.5 degrees C. Sixty-one specimens were obtained from inpatients and 52 were obtained from outpatients. Shigella sp. were isolated from 33%, enterotoxigenic Escherichia coli from 16%, Giardia lamblia from 4%, and rotavirus from 1% of 113 stool samples obtained from inpatient (61) and outpatient (52) troops with diarrhea. Bacterial isolates obtained in Somalia were resistant to doxycycline (78%), ampicillin (54%), and sulfamethoxazole (49%), but uniformly sensitive to ciprofloxacin. With the exception of 10 Shigella sonnei isolates that were linked epidemiologically to one eating facility, bacterial pathogens occurred sporadically and demonstrated a wide variation of serotypes and antibiotic sensitivity patterns. Additionally, three of 11 paired sera collected from persons with nausea, vomiting, and watery diarrhea demonstrated a four-fold or greater increase in titer to Norwalk virus antibody. These data indicate that large outbreaks of diarrheal disease did not occur; however, highly drug-resistant enteric bacteria, and to a lesser extent viral and parasitic pathogens, were important causes of morbidity among U.S. troops in Somalia. C1 USN,MED RES INST,BETHESDA,MD 20889. USN,MED CTR,DIV INFECT DIS,SAN DIEGO,CA 92134. WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,DIV PREVENT MED,WASHINGTON,DC 20307. USN,ENVIRONM & PREVENT MED UNIT 7,NAPLES,ITALY. USN,MED RES UNIT 3,CAIRO,EGYPT. USN,ENVIRONM & PREVENT MED UNIT 6,HONOLULU,HI. ARMED FORCES RES INST MED SCI,BANGKOK 10400,THAILAND. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. BAYLOR COLL MED,TEXAS MED CTR,DIV MOLEC VIROL,HOUSTON,TX 77030. NR 32 TC 51 Z9 51 U1 1 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD FEB PY 1995 VL 52 IS 2 BP 188 EP 193 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA QL877 UT WOS:A1995QL87700017 PM 7872452 ER PT J AU ROSENBERG, M SCHOOLER, C SCHOENBACH, C ROSENBERG, F AF ROSENBERG, M SCHOOLER, C SCHOENBACH, C ROSENBERG, F TI GLOBAL SELF-ESTEEM AND SPECIFIC SELF-ESTEEM - DIFFERENT CONCEPTS, DIFFERENT OUTCOMES SO AMERICAN SOCIOLOGICAL REVIEW LA English DT Article ID SOCIAL-CLASS AB In this paper, we attempt to shed light on the nature of relevance of, and relationship between global self-esteem and specific self-esteem. We marshal evidence that the two types of self-esteem may have strikingly different consequences, global self-esteem being more relevant to psychological wellbeing, and specific self-esteem being more relevant to behavior. We use linear structural equation causal modeling to test this hypothesis for the case of global self-esteem (Rosenberg 1979) and specific (academic) self-esteem. Our findings show that, while global self-esteem is more strongly related to measures of psychological well-being, specific (academic) self-esteem is a much better predictor of school performance. Other findings indicate that the degree to which specific academic self-esteem affects global self-esteem, particularly the positive component of global self-esteem, is a function of how highly academic performance is personally valued. C1 NIMH,SOCIOENVIRONM STUDIES LAB,BETHESDA,MD 20892. UNIV MARYLAND,COLLEGE PK,MD 20742. WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,DEPT MIL PSYCHIAT,WASHINGTON,DC 20307. UNIFORMED SERV UNIV HLTH SCI,DEPT PSYCHIAT,BETHESDA,MD 20814. NR 61 TC 411 Z9 425 U1 14 U2 138 PU AMER SOCIOLOGICAL ASSOC PI WASHINGTON PA 1722 N ST NW, WASHINGTON, DC 20036-2981 SN 0003-1224 J9 AM SOCIOL REV JI Am. Sociol. Rev. PD FEB PY 1995 VL 60 IS 1 BP 141 EP 156 DI 10.2307/2096350 PG 16 WC Sociology SC Sociology GA RC478 UT WOS:A1995RC47800009 ER PT J AU FOX, KM KIMURA, S PLATO, CC KITAGAWA, T AF FOX, KM KIMURA, S PLATO, CC KITAGAWA, T TI BILATERAL ASYMMETRY IN BONE WEIGHT AT VARIOUS SKELETAL SITES OF THE RAT SO ANATOMICAL RECORD LA English DT Article DE BILATERAL ASYMMETRY; BONE WEIGHT; RAT SKELETON ID FUNCTIONAL ASYMMETRY; MASS; MEN AB Background: Morphological and functional asymmetry in the limbs has generally been regarded as a human characteristic that is of genetic or of both genetic and environmental origin. The aim of this study was to determine the presence of lateral dominance in bone weight of the forelimb of the rat. Methods: Wistar rats (77) were used, 45 controls and 32 experimental animals, implanted with a steel weight subcutaneously under the right forelimb. Bones examined for bilateral asymmetry in bone weight were the mandibula, the bones of fore- and hindlimbs, calcaneus, and talus of the tarsus. The weight of each dry bone was measured to the nearest milligram. Results: Significant bilateral asymmetry in the forelimb was evident in male and female rats, with the left side having more bone mass than the right. Bilateral differences were more pronounced in the females than the male rats. Greater asymmetry was evident in the experimental group compared to the control rats. Conclusions: These findings demonstrate that asymmetry is present not only in humans, but also in lower animals such as rats. Greater asymmetry in the experimental rat group is indicative of the influence of environmental factors or physical stress on asymmetry. We conclude that genetics might control the development of asymmetry, but physical stress may alter the functional expression of the asymmetry. (C) 1995 Wiley-Liss, Inc. C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NIHON UNIV,SCH DENT,DEPT ANAT 1,TOKYO 101,JAPAN. RP FOX, KM (reprint author), UNIV MARYLAND,DEPT EPIDEMIOL & PREVENT MED,660 W REDWOOD ST,BALTIMORE,MD 21201, USA. NR 24 TC 12 Z9 13 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0003-276X J9 ANAT REC JI Anat. Rec. PD FEB PY 1995 VL 241 IS 2 BP 284 EP 287 DI 10.1002/ar.1092410215 PG 4 WC Anatomy & Morphology SC Anatomy & Morphology GA QH452 UT WOS:A1995QH45200014 PM 7710144 ER PT J AU MERCADOASIS, LB OLDFIELD, EH CUTLER, GB AF MERCADOASIS, LB OLDFIELD, EH CUTLER, GB TI PITUITARY-TUMOR HEMORRHAGE IN CUSHING DISEASE SO ANNALS OF INTERNAL MEDICINE LA English DT Note ID APOPLEXY C1 NIH,BETHESDA,MD 20892. NR 12 TC 8 Z9 8 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD FEB 1 PY 1995 VL 122 IS 3 BP 189 EP 190 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QD733 UT WOS:A1995QD73300006 PM 7810937 ER PT J AU LIEBMANN, J GURTLER, J AF LIEBMANN, J GURTLER, J TI COMBINATION INTRAVENTRICULAR THERAPY WITH THIOTEPA AND CYTARABINE IN MENINGEAL CARCINOMATOSIS DUE TO BREAST-CANCER - IN-VITRO EVIDENCE FOR SUPRAADDITIVE CYTOTOXICITY SO ANTI-CANCER DRUGS LA English DT Article DE BREAST CANCER; CYTARABINE; MENINGES; THIOTEPA ID AGENTS AB Metastatic spread of tumors to the meninges is a frequent complication of many malignancies and is difficult to treat. We describe the case of a patient who developed carcinomatous involvement of the meninges from a breast adenocarcinoma. Despite intrathecal treatment with conventional and experimental agents, the patient's cerebrospinal fluid (CSF) was not cleared of malignant cells until thiotepa and cytarabine were given in combination. This clinical observation led us to assess the in vitro activity of the combination of thiotepa and cytarabine in clonogenic cell survival assays. The human breast adenocarcinoma cell line MCF-7(WT) and its doxorubicin-resistant variant MCF-7(ADR) were exposed to thiotepa and cytarabine either singly or in combination. We have found that the combination of the two drugs resulted in more than additive cytotoxicity than would have been predicted from the cytotoxicty of either drug given alone. We discuss the implications of these findings on the clinical management of patients with carcinomatous spread to the meninges. C1 NCI,RADIAT BIOL BRANCH,BETHESDA,MD 20895. NR 13 TC 2 Z9 2 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD FEB PY 1995 VL 6 IS 1 BP 40 EP 44 DI 10.1097/00001813-199502000-00004 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA QJ112 UT WOS:A1995QJ11200004 PM 7756682 ER PT J AU YU, JA PAPAVASILIOU, V RHIM, J GOLTZMAN, D KREMER, R AF YU, JA PAPAVASILIOU, V RHIM, J GOLTZMAN, D KREMER, R TI VITAMIN-D ANALOGS - NEW THERAPEUTIC AGENTS FOR THE TREATMENT OF SQUAMOUS CANCER AND ITS ASSOCIATED HYPERCALCEMIA SO ANTI-CANCER DRUGS LA English DT Article DE ANALOGS; HYPERCALCEMIA; SQUAMOUS CANCER; VITAMIN-D ID HORMONE-LIKE PEPTIDE; HUMAN KERATINOCYTES; TUMOR PROGRESSION; DIFFERENTIATION; EXPRESSION; PROLIFERATION; SECRETION; ONCOGENE; CALCIUM; MC-903 AB We have examined the in vitro effects of 1,25 dihydroxyvitamin D-3 [1,25(OH)(2)D-3] and of two side-chain modified analogs of 1,25(OH)(2)D-3 (EB1089 and MC903) on cell growth and parathyroid hormone related peptide (PTHRP) production in immortalized (HPK1A) and neoplastic (HPK1A-ras) keratinocytes. Cell proliferation was strongly inhibited by 1,25(OH)(2)D-3 and its analogs in HPK1A cells, and in this system EB1089 was 10-100 times more potent than 1,25(OH)(2)D-3 or MC903. A similar effect on cell proliferation was observed in HPK1A-ras cells; however, 10-fold higher concentrations of 1,25(OH)(2)D-3 or its analogs were required. We also observed a strong and dose-dependent inhibitory effect of these compounds on PTHRP secretion and gene expression. In both immortalized and neoplastic keratinocytes, EB1089 was 10-100 times more potent than 1,25(OH)(2)D-3 or MC903 on inhibiting PTHRP production. However, although effective in HPK1A-ras cells, 10-fold higher concentrations of 1,25(OH)(2)D-3 or its analogs were required to produce similar actions in this neoplastic model. These studies therefore demonstrate that a 1,25(OH)(2)D-3 analog with low calcemic potency in vivo (EB1089) can inhibit keratinocyte proliferation and PTHRP production by such cells with greater potency than 1,25(OH)(2)D-3. The observed effects of such analogs in neoplastic keratinocytes predicts their potential usefulness in vivo in inhibiting squamous cancer growth and its associated hypercalcemia. C1 MCGILL UNIV,DEPT MED,MONTREAL,PQ,CANADA. MCGILL UNIV,DEPT PHYSIOL,MONTREAL,PQ,CANADA. NCI,MOLEC & CELL BIOL LAB,BETHESDA,MD. NR 26 TC 27 Z9 27 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD FEB PY 1995 VL 6 IS 1 BP 101 EP 108 DI 10.1097/00001813-199502000-00012 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA QJ112 UT WOS:A1995QJ11200012 PM 7756673 ER PT J AU COPUR, S DAHUT, W CHU, E ALLEGRA, CJ AF COPUR, S DAHUT, W CHU, E ALLEGRA, CJ TI BONE-MARROW APLASIA AND SEVERE SKIN RASH AFTER A SINGLE LOW-DOSE OF METHOTREXATE SO ANTI-CANCER DRUGS LA English DT Note DE HYPERSENSITIVITY; METHOTREXATE; PANCYTOPENIA; RASH ID CANCER; PHARMACOKINETICS; CHEMOTHERAPY; HEAD; NECK AB A 64 year old man with recurrent metastatic squamous cell carcinoma of the head and neck developed severe skin rash and bone marrow aplasia 4 and 7 days, respectively, following a single dose of 40 mg/m(2) methotrexate (MTX). Skin rash involved regions of the face, lower abdomen, back, buttocks and both upper thighs. Biopsy of the skin rash demonstrated superficial perivascular lymphocytic infiltrate and was consistent with a drug reaction. Peripheral blood count revealed pancytopenia and a bone marrow biopsy was consistent with aplasia. Blood counts returned to normal 6 days after institution of granulocyte colony stimulating factor therapy. In the absence of mucositis or diarrhea, severe dermatologic toxicity following a single low dose of the drug suggests an 'allergic' or acute hypersensitivity reaction to MTX in this patient. Development of an extensive skin rash following a single dose of MTX may be an early warning sign for life-threatening bone marrow aplasia. C1 NATL NAVAL MED CTR, DIV HEMATOL ONCOL, BETHESDA, MD 20889 USA. NCI, NAVY MED ONCOL BRANCH, BETHESDA, MD 20889 USA. NR 28 TC 3 Z9 3 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD FEB PY 1995 VL 6 IS 1 BP 154 EP 157 DI 10.1097/00001813-199502000-00018 PG 4 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA QJ112 UT WOS:A1995QJ11200018 PM 7538828 ER PT J AU ESPINELINGROFF, A DAWSON, K PFALLER, M ANAISSIE, E BRESLIN, B DIXON, D FOTHERGILL, A PAETZNICK, V PETER, J RINALDI, M WALSH, T AF ESPINELINGROFF, A DAWSON, K PFALLER, M ANAISSIE, E BRESLIN, B DIXON, D FOTHERGILL, A PAETZNICK, V PETER, J RINALDI, M WALSH, T TI COMPARATIVE AND COLLABORATIVE EVALUATION OF STANDARDIZATION OF ANTIFUNGAL SUSCEPTIBILITY TESTING FOR FILAMENTOUS FUNGI SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID BROTH MACRODILUTION; MULTICENTER EVALUATION; INOCULUM PREPARATION; YEASTS AB The purpose of the study was to evaluate the interlaboratory agreement of broth dilution susceptibility methods for five species of conidium-forming (size range, 2 to 7 mu m) filamentous fungi. The methods used included both macro- and microdilution methods that were adaptations of the proposed reference method of the National Committee for Clinical Laboratory Standards for yeasts (m27-P). The MICs of amphotericin B, fluconazole, itraconazole, miconazole, and ketoconazole were determined in six centers by both macro- and microdilution tests for 25 isolates of Aspergillus flavus, Aspergillus fumigatus, Pseudallescheria boydii, Rhizopus arrhizus, and Sporothrix schenckii. All isolates produced clearly detectable growth within 1 to 4 days at 35 degrees C in the RPMI 1640 medium. Colony counts of 0.4 x 10(6) to 3.3 x 106 CFU/ml (mean, 1.4 x 10(6) CFU/ml) were demonstrated in 90% of the 148 inoculum preparations. Overall, good intralaboratory agreement was demonstrated with amphotericin B, fluconazole, and ketoconazole MICs (90 to 97%). The agreement was lower with itraconazole MICs (59 to 79% median). Interlaboratory reproducibility demonstrated similar results: 90 to 100% agreement with amphotericin B, fluconazole, miconazole, and ketoconazole MICs and 59 to 98% with itraconazole MICs. Among the species tested, the MICs for S. schenckii showed the highest variability. The results of the study imply that it may be possible to develop a reference method for antifungal susceptibility testing of filamentous fungi. C1 UNIV IOWA,COLL MED,IOWA CITY,IA. NEW YORK STATE DEPT HLTH,ALBANY,NY 12201. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. NCI,BETHESDA,MD 20892. MD ANDERSON CANC CTR,HOUSTON,TX. RP ESPINELINGROFF, A (reprint author), VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DIV INFECT DIS,BOX 980049,RICHMOND,VA 23298, USA. NR 14 TC 186 Z9 192 U1 0 U2 6 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 FEB PY 1995 VL 39 IS 2 BP 314 EP 319 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA QE777 UT WOS:A1995QE77700006 PM 7726488 ER PT J AU MCMAHON, JB CURRENS, MJ GULAKOWSKI, RJ BUCKHEIT, RW LACKMANSMITH, C HALLOCK, YF BOYD, MR AF MCMAHON, JB CURRENS, MJ GULAKOWSKI, RJ BUCKHEIT, RW LACKMANSMITH, C HALLOCK, YF BOYD, MR TI MICHELLAMINE-B, A NOVEL PLANT ALKALOID, INHIBITS HUMAN IMMUNODEFICIENCY VIRUS-INDUCED CELL-KILLING BY AT LEAST 2 DISTINCT MECHANISMS SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID TYPE-1 REVERSE-TRANSCRIPTASE; POTENT INHIBITOR; NATURAL-PRODUCTS; ESCHERICHIA-COLI; ANTI-HIV AB Studies of the mechanism of action of michellamine B, a never anti-human immunodeficiency virus (HN) alkaloid from the tropical plant Ancistrocladus korupensis, have revealed that the compound acts at two distinct stages of the HN life cycle. The compound had no direct effect on HIV virions and did not block the initial binding of HIV to target cells. Postinfection time course studies revealed that the agent partially inhibited HN-induced cell killing and syncytium formation when added up to 48 h following acute infection; however, viral reproduction was fully inhibited only when the compound was added immediately after infection. Time-limited treatments of HIV-infected cells revealed that michellamine B had to be present continuously to provide maximum antiviral protection. HIV replication in cells in which infection was already fully established or in chronically infected cells was unaffected by michellamine B, Biochemical studies showed that michellamine B inhibited the enzymatic activities of reverse transcriptases (RTs) from both HIV type 1 and HIV type 2 as well as two different nonnucleoside drug-resistant RTs with specific amino acid substitutions. In addition, human DNA polymerases alpha and beta were inhibited by the alkaloid, Michellamine B exerted a potent dose-dependent inhibition of Cell fusion in two independent cell-based fusion assays. Thus, michellamine B acts both at an early stage of the HIV life cycle by inhibiting RT as well as at later stages by inhibiting cellular fusion and syncytium formation. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. FREDERICK CANC RES & DEV CTR,SO RES INST,DIV VIROL RES,FREDERICK,MD 21701. NR 26 TC 64 Z9 66 U1 0 U2 2 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 FEB PY 1995 VL 39 IS 2 BP 484 EP 488 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA QE777 UT WOS:A1995QE77700037 PM 7537029 ER PT J AU SEKI, K CHEN, HC HUANG, KP AF SEKI, K CHEN, HC HUANG, KP TI DEPHOSPHORYLATION OF PROTEIN-KINASE-C SUBSTRATES, NEUROGRANIN, NEUROMODULIN, AND MARCKS, BY CALCINEURIN AND PROTEIN PHOSPHATASE-1 AND PHOSPHATASE-2A SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE CALCINEURIN; PROTEIN PHOSPHATASES; NEUROGRANIN; NEUROMODULIN; MARCKS ID CALMODULIN-BINDING-PROTEIN; GROWTH-ASSOCIATED PROTEIN; CATALYTIC SUBUNIT; MOLECULAR-CLONING; RAT-BRAIN; CELLULAR SUBSTRATE; 87-KDA PROTEIN; PHOSPHORYLATION; IDENTIFICATION; PURIFICATION AB Neurogranin, neuromodulin, and MARCKS are among the most prominent substrates of protein kinase C (PKC) in the mammalian brain. These phosphoproteins were dephosphorylated by three isoforms of rat brain calcineurin, also known as calmodulin (CaM)-dependent protein phosphatase (CaMPP). The three CaMPP isozymes dephosphorylate neurogranin, the most favorable substrate among the three tested, with subtle differences in their responses to divalent metal ions, Mn2+ and Ni2+. Dephosphorylation of neurogranin by all three CaMPP isozymes, CaMPP-1, -2, and -3, were stimulated to a higher extent by Mn2+ than by Ni2+ in the presence of CaM and Ca2+. The K-m values of neurogranin in the presence of Mn2+ were lower than those in the presence of Ni2+ for CaMPP-1 and -2,but that for CaMPP-3 was comparable with either divalent metal ion. The V-max values were higher in the presence of Mn2+ than those of Ni2+ for all three isozymes. Neurogranin and neuromodulin, both phosphorylated by PKC at a single site, were dephosphorylated completely by CaMPP; however, MARCKS, phosphorylated by PKC at three sites, was partially dephosphorylated by this phosphatase. A higher extent of dephosphorylation of MARCKS could be achieved by the combination of CaMPP and protein phosphatase 2A and a complete dephosphorylation of this protein was observed with protein phosphatase 1. Protein phosphatase 1 and 2A were also effective in a complete dephosphorylation of neurogranin and neuromodulin. Amino acid sequence analysis of the tryptic phosphopeptides derived from MARCKS dephosphorylated by CaMPP and protein phosphatase 2A revealed that the former preferentially dephosphorylated Ser(155) and the latter Ser(162) of rat brain MARCKS. Both phosphatases dephosphorylated poorly of Ser(151). Because of the high concentration of CaMPP in the brain and the colocalization of this phosphatase with major PRC substrates in the various brain regions, it is likely that CaMPP is a phosphatase with potential to reverse the action of PKC. (C) 1995 Academic Press, Inc. C1 NICHHD, ENDOCRINOL & REPROD RES BRANCH, BETHESDA, MD 20892 USA. NR 56 TC 65 Z9 65 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 EI 1096-0384 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD FEB 1 PY 1995 VL 316 IS 2 BP 673 EP 679 DI 10.1006/abbi.1995.1090 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QH029 UT WOS:A1995QH02900003 PM 7864622 ER PT J AU HASHIMOTOUOSHIMA, M HASCALL, VC MACCALLUM, DK YANAGISHITA, M AF HASHIMOTOUOSHIMA, M HASCALL, VC MACCALLUM, DK YANAGISHITA, M TI BIOSYNTHESIS OF PROTEOGLYCANS AND HYALURONIC-ACID BY RAT ORAL EPITHELIAL-CELLS (KERATINOCYTES) IN-VITRO SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID HEPARAN-SULFATE PROTEOGLYCANS; OVARIAN GRANULOSA-CELLS; INTRACELLULAR DEGRADATIVE PATHWAYS; KERATINIZING SQUAMOUS EPITHELIUM; HUMAN GINGIVAL EPITHELIUM; CONNECTIVE-TISSUE; SURFACE PROTEOGLYCAN; DERMATAN SULFATE; CHONDROITIN SULFATE; CULTURE AB Biosynthesis of complex carbohydrates, including sulfated glycoproteins, hyaluronic acid (HA), and proteoglycans (PGs), synthesized by rat oral epithelial cells (keratinocytes) in culture were studied by metabolic labeling protocols using [S-35]sulfate and [H-3]glucosamine in combination with differential enzymatic digestion and analytical gel filtration. The epithelial cells synthesized a major sulfated glycoprotein species with an apparent molecular size similar to 50 kDa, which accounted for approximately 46% of the total S-35 incorporation. HA was a relatively minor component of H-3-labeled macromolecules (similar to 4% of the total H-3 incorporation), and almost all of it was secreted into the medium. PGs accounted for approximately half of the S-35 incorporation, of which about 30% was secreted into the medium and the remainder associated with the cell layer. The majority of PGs (75% of the secreted and 97% of the cell-associated) contained heparan sulfate (HS) and had an apparent molecular weight of similar to 150,000. Cell-associated HSPGs had a core protein of similar to 70 kDa with HS chains of similar to 64 kDa, while HSPG in the medium had a core protein of similar to 50 kDa with HS chains of the same average size as those of the cell-associated HSPG. Of the total cell-associated HSPGs, glycosylphosphatidyl inositol-anchored forms, plasma membrane intercalated forms and those associated with basolateral pericellular matrix accounted for similar to 3%, 56% and similar to 4% of the total, respectively. Approximately one third of the cell-associated HSPGs were intracellular components most likely generated through intracellular degradation processes following endocytosis. Cell surface HSPGs synthesized by keratinocytes may be involved in some biological roles such as the regulation of normal epithelial turnover and defense mechanisms involving interactions with various oral pathogens. (C) 1995 Academic Press, Inc. C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. NR 44 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD FEB 1 PY 1995 VL 316 IS 2 BP 724 EP 732 DI 10.1006/abbi.1995.1096 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QH029 UT WOS:A1995QH02900009 PM 7864627 ER PT J AU KITZLER, J HILL, E HARDMAN, R REDDY, N PHILPOT, R ELING, TE AF KITZLER, J HILL, E HARDMAN, R REDDY, N PHILPOT, R ELING, TE TI ANALYSIS AND QUANTITATION OF SPLICING VARIANTS OF THE TPA-INDUCIBLE PGHS-1 MESSENGER-RNA IN RAT TRACHEAL EPITHELIAL-CELLS SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE PROSTAGLANDIN H SYNTHASE; TPA; RAT TRACHEAL EPITHELIAL CELLS; QUANTITATIVE PCR ID PROSTAGLANDIN ENDOPEROXIDE SYNTHASE; MESSENGER-RNA; G/H SYNTHASE; COMPLEMENTARY-DNA; PHORBOL ESTER; CDNA CLONING; EXPRESSION; GENE; CYCLOOXYGENASE; PROTEIN AB Previously we reported that 12-myristate 13-acetate diester (TPA) and dexamethasone regulate the expression of a putative prostaglandin G/H synthase-1 (PGHS-1) gene in a transformed, immortalized rat tracheal epithelial cell line (EGV-6), Here we report the cloning and sequencing of the cDNA for this gene, Two transcripts of similar size but differing in their 5' ends were detected, One transcript contains the complete 5' coding and noncoding regions, while the other form has an apparently intronic sequence in place of these regions, This aberrantly spliced form lacks codons 1-36, Northern analysis and quantitative PCR indicated that more than 90% of the PGHS-1 mRNA in EGV-6 cells has the aberrantly spliced 5' end. TPA treatment increases the expression of only the complete PGHS-1 mRNA, elevating it to 50% of the total PGHS-1 transcript pool, Levels of the aberrant mRNA are not affected by TPA treatment, A comparison among EGV-6 cells, primary rat tracheal epithelial (RTE) cultures, and rat fibroblasts showed that all three cell lines have similar levels of the aberrantly spliced PGHS-1 mRNA. RTE cells and fibroblasts, unlike EGV-6 cells, also contain properly spliced PGHS-1 mRNA, at levels 100-fold higher than the level of aberrant PGHS-1 mRNA, TPA does not regulate either of the PGHS-1 transcripts in RTE or rat fibroblast cells, These results confirm the induction of functional PGHS-1 mRNA by TPA only in EGV-6 cells. (C) 1995 Academic Press, Inc. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709. NR 33 TC 24 Z9 26 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD FEB 1 PY 1995 VL 316 IS 2 BP 856 EP 863 DI 10.1006/abbi.1995.1115 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QH029 UT WOS:A1995QH02900028 PM 7864644 ER PT J AU DONG, AC HUANG, P CAUGHEY, B CAUGHEY, WS AF DONG, AC HUANG, P CAUGHEY, B CAUGHEY, WS TI INFRARED-ANALYSIS OF LIGAND-INDUCED AND OXIDATION-INDUCED CONFORMATIONAL-CHANGES IN HEMOGLOBINS AND MYOGLOBINS SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE FT-IR SPECTROSCOPY; HEMOGLOBIN; MYOGLOBIN ID PROTEIN SECONDARY STRUCTURE; CIRCULAR-DICHROISM; CYTOCHROME-C; SPERM WHALE; RESOLUTION; SPECTROSCOPY; SPECTRA; WATER; METMYOGLOBIN; REFINEMENT AB Effects of the binding of O-2 and CO to heme iron (II) of deoxy forms and of the oxidation of deoxy forms to aquoiron (III) complexes on the infrared spectra of hemoglobins and myoglobins have been examined, Spectra were measured for aqueous solutions 3-4 mM in heme of human, bovine, and equine hemoglobins and sperm whale, bovine, and equine myoglobins in 10 mM sodium phosphate buffer, pH 7.4, at 20 degrees C, All ligand binding and oxidation reactions resulted in similar spectral shifts in the region 1665 to 1670 cm(-1), a portion of the amide I region assignable to beta-turn structure, There were no other significant changes in the amide I region, a finding consistent with no other alterations in secondary structure, The major bands near 1655 cm(-1) associated with alpha-helices were consistently at 2 cm(-1) lower wavenumber for myoglobins than for hemoglobins, The changes in solution infrared spectra observed in this study may result at least in part from conformational changes at the FG corner associated with movements of F and E helices that have been noted previously in crystal structures. (C) 1995 Academic Press, Inc. C1 NIAID,ROCKY MT LABS,HAMILTON,MT 59840. RP DONG, AC (reprint author), COLORADO STATE UNIV,DEPT BIOCHEM & MOLEC BIOL,FT COLLINS,CO 80523, USA. NR 45 TC 28 Z9 28 U1 1 U2 9 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD FEB 1 PY 1995 VL 316 IS 2 BP 893 EP 898 DI 10.1006/abbi.1995.1120 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QH029 UT WOS:A1995QH02900033 PM 7864648 ER PT J AU AKISKAL, HS MASER, JD ZELLER, PJ ENDICOTT, J CORYELL, W KELLER, M WARSHAW, M CLAYTON, P GOODWIN, F AF AKISKAL, HS MASER, JD ZELLER, PJ ENDICOTT, J CORYELL, W KELLER, M WARSHAW, M CLAYTON, P GOODWIN, F TI SWITCHING FROM UNIPOLAR TO BIPOLAR-II - AN 11-YEAR PROSPECTIVE-STUDY OF CLINICAL AND TEMPERAMENTAL PREDICTORS IN 559 PATIENTS SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID MANIC-DEPRESSIVE ILLNESS; BORDERLINE PERSONALITY-DISORDER; MAJOR DEPRESSION; ATYPICAL DEPRESSION; FAMILY; RELIABILITY; CRITERIA; ADOLESCENTS; CYCLOTHYMIA; PROPHYLAXIS AB Background: Given the therapeutic and prognostic importance of the unipolar-bipolar dichotomy, predicting which patients will become bipolar subsequent to index diagnosis of major depressive disorder (MDD) is of paramount clinical significance. We sought to characterize the profile of patients with MDD who would convert to the more subtle bipolar subtype (known as BPII) on the basis of clinical and personality variables obtained during MDD episodes. Methods: A total of 559 patients, comprehensively evaluated with the Schedule of Affective Disorders and Schizophrenia and ''unipolar'' MDD at entry, were administered 17 self-report personality measures. Hypomanic and manic episodes were systematically recorded over a prospective observation period of up to 11 years. We compared 48 converters to BPII (8.6%) with 22 converters to bipolar I (BPI) (3.9%) and the remaining larger group of unipolar patients. Results: Except for greater acuteness, severity, and psychotic symptomatology, BPI converters were essentially similar to MDD nonconverters. By contrast, BPII converters were robustly distinguished from those with MDD who remained unipolar on the basis of self-report measures along the newly derived factors of Mood Lability, Energy-Activity, and Daydreaming. This profile was associated with early age at onset of MDD and pleomorphic psychopathology beyond the usual affective realm, high rates of substance abuse, as well as educational, marital, and occupational disruption and minor antisocial acts prior to discrete hypomanic episodes. Overall, BPII switchers had a more protracted and tempestuous course with shorter well intervals. ''Habitual self'' descriptions of temperamental instability during MDD episodes provided useful clinical information for predicting which depressed patients will switch to BPII, attaining a sensitivity of 91% for all three factors combined (23 items); Mood Lability alone (nine items) was the most specific predictor (86%), though of lower sensitivity (42%). Conclusions: The BPII subtype is best understood by such lability intruding into, and possibly its accentuation during, depressive episodes, thereby creating an intimate interweaving of trait and state. Clinicians must note that the foregoing temperamental profile appears more fundamental in defining the affective dysregulation of the BPII subtype than hypomanic episodes emphasized in DSM-IV. C1 NIMH,COLLABORAT PROGRAM PSYCHOBIOL DEPRESS,ROCKVILLE,MD 20857. DATAMAX INC,ROCKVILLE,MD. FU NIMH NIH HHS [R01 MH025478] NR 66 TC 510 Z9 518 U1 3 U2 29 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 FEB PY 1995 VL 52 IS 2 BP 114 EP 123 PG 10 WC Psychiatry SC Psychiatry GA QF549 UT WOS:A1995QF54900003 PM 7848047 ER PT J AU MANJI, HK CHEN, G SHIMON, H HSIAO, JK POTTER, WZ BELMAKER, RH AF MANJI, HK CHEN, G SHIMON, H HSIAO, JK POTTER, WZ BELMAKER, RH TI GUANINE-NUCLEOTIDE-BINDING PROTEINS IN BIPOLAR AFFECTIVE-DISORDER - EFFECTS OF LONG-TERM LITHIUM TREATMENT SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID ADENYLATE-CYCLASE ACTIVITY; STIMULATORY G-PROTEIN; KINASE-C; SIGNAL TRANSDUCTION; HUMAN-PLATELET; CYCLIC-AMP; RAT CORTEX; HEREDITARY OSTEODYSTROPHY; ADRENERGIC-RECEPTORS; PERTUSSIS TOXIN AB Background: This study examines recent suggestions from a number of investigators that signal-transducing guanine nucleotide-binding (G) proteins may be involved in the pathophysiology of bipolar affective disorder and may represent molecular targets for lithium's mood-stabilizing actions. Methods: We used selective antibodies to quantitate the levels of the G protein alpha subunits that regulate adenylate cyclase activity (G alpha(s) and G alpha(i2)) and phosphoinositide turnover (G alpha(q/11)). We also quantitated levels of pertussis toxin-catalyzed phosphate 32-labeled adenosine diphosphate ([P-32]ADP) ribosylation in platelet and leukocyte membranes from a group of 14 untreated (predominantly manic) patients with bipolar affective disorder, 20 lithium-treated euthymic patients with bipolar affective disorder, and 11 healthy controls. Results: In both tissues, the immunolabeling of the 45-kd form of G alpha(s) was higher in the bipolar affective disorder group considered as a whole (treated or untreated) compared with controls, effects that reached statistical significance in the leukocyte membranes. There were no significant differences in the immunolabeling of G alpha(i1/2), G alpha(q/11), or pertussis toxin-catalyzed [P-32]ADP ribosylation in either tissue in the untreated bipolar affective disorder group compared with controls. In both tissues, lithium-treated subjects demonstrated lower levels of G alpha(q/11) and higher levels of pertussis toxin-catalyzed [P-32]ADP-ribosylation, which reached significance in the platelet membranes. Conclusions: Our results are complementary to the previously reported findings of elevated G alpha(s) levels in postmortem brain tissue from patients with bipolar affective disorder and in mononuclear leukocytes obtained from depressed patients with bipolar (but not unipolar) affective disorder. The significantly higher levels of pertussis toxin-catalyzed [P-32]ADP ribosylation in the subjects receiving long-term lithium-treatment replicates our findings in rat cortex and in healthy volunteers and adds to the growing body of evidence implicating G alpha(i) as a target of lithium's actions. C1 BEN GURION UNIV NEGEV,BEER SHEVA,ISRAEL. RP MANJI, HK (reprint author), NIMH,CLIN PHARMACOL SECT,EXPTL THERAPEUT BRANCH,BLDG 10,ROOM 2D46,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Chen, Guang/A-2570-2017 NR 81 TC 82 Z9 84 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 FEB PY 1995 VL 52 IS 2 BP 135 EP 144 PG 10 WC Psychiatry SC Psychiatry GA QF549 UT WOS:A1995QF54900005 PM 7848049 ER PT J AU MATSUKI, Y AMIZUKA, N WARSHAWSKY, H GOLTZMAN, D YAMADA, Y AF MATSUKI, Y AMIZUKA, N WARSHAWSKY, H GOLTZMAN, D YAMADA, Y TI GENE-EXPRESSION OF EPIMORPHIN IN RAT INCISOR AMELOBLASTS SO ARCHIVES OF ORAL BIOLOGY LA English DT Note DE EPIMORPHIN; IN SITU HYBRIDIZATION; RAT INCISOR; AMELOBLASTS ID MORPHOGENESIS; HPC-1 AB Epimorphin has been recently identified as an important factor in the morphogenesis of epithelial cells. A cDNA encoding epimorphin from skin of newborn mice was cloned by the polymerase chain-reaction technique before the preparation of digoxigenin-labelled cRNA probes. In situ hybridization of longitudinal sections of rat incisors revealed a distinct pattern of expression of epimorphin mRNA in the ameloblast layer. Epimorphin mRNA was detected from the presecretory stage up to the beginning of the maturation stage of amelogenesis. With the identification of this expression by epithelial-derived cells, i.e. ameloblasts, it is thought likely that epimorphin is one of the factors that modulate the differentiation cascade of ameloblasts in the course of amelogenesis. C1 NIIGATA UNIV, SCH DENT, NIIGATA 951, JAPAN. MCGILL UNIV, DEPT MED, MONTREAL, PQ H3A 1A1, CANADA. RP MATSUKI, Y (reprint author), NIDR, DEV BIOL LAB, BETHESDA, MD 20892 USA. NR 15 TC 9 Z9 9 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0003-9969 J9 ARCH ORAL BIOL JI Arch. Oral Biol. PD FEB PY 1995 VL 40 IS 2 BP 161 EP 164 DI 10.1016/0003-9969(94)00150-A PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA QN693 UT WOS:A1995QN69300011 PM 7794129 ER PT J AU PANZER, VP BANDINELLI, S HALLETT, M AF PANZER, VP BANDINELLI, S HALLETT, M TI BIOMECHANICAL ASSESSMENT OF QUIET STANDING AND CHANGES ASSOCIATED WITH AGING SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article ID ELDERLY PEOPLE; OLDER-PEOPLE; SWAY; FALLS; COMMUNITY; HOME; AGE AB The kinematics of standing balance were analyzed in 24 normal subjects, aged 21 to 78 years, to examine differences attributable to age, visual input, and sex. Movements of individual body segments, displacement of the center of gravity (COG), and position of the center of pressure (COP) were measured, and total path length and variability about the mean position were derived from the resulting values. Aging was associated with an increase in variability of the COG, head, and hip, but not in path length. The changes, which may be clinically interpreted as excess postural sway, do not show stability deficits as a consequence of aging. On the contrary, older subjects seem to adopt a postural control strategy that achieves comparable stability during quiet standing. Eye closure increased the anterior-posterior COP path length without corresponding changes in the COG, indicating an increase in small accelerations without associated instability. There was more medial-lateral movement in women than in men. Quantitative electromyographic measures showed that, in general, quiet standing requires very little muscular activity. We conclude that the task of quiet standing produces no evidence of postural instability concurrent with aging. The altered postural control strategy may be less effective when balance is suddenly or severely compromised. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BLDG 10,ROOM SN226,BETHESDA,MD 20892. OREGON HLTH SCI UNIV,CTR RES OCCUPAT & ENVIRONM TOXICOL,PORTLAND,OR 97201. OSPED INRCA I FRATICINI,FLORENCE,ITALY. NR 33 TC 99 Z9 101 U1 2 U2 10 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD FEB PY 1995 VL 76 IS 2 BP 151 EP 157 DI 10.1016/S0003-9993(95)80024-7 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA QG050 UT WOS:A1995QG05000005 PM 7848073 ER PT J AU ADACHI, J GOMEZ, M SMITH, CC STERNBERG, EM AF ADACHI, J GOMEZ, M SMITH, CC STERNBERG, EM TI ACCUMULATION OF 3-(PHENYLAMINO)ALANINE, A CONSTITUENT IN L-TRYPTOPHAN PRODUCTS IMPLICATED IN EOSINOPHILIA-MYALGIA-SYNDROME, IN BLOOD AND ORGANS OF THE LEWIS RATS SO ARCHIVES OF TOXICOLOGY LA English DT Article DE 3-(PHENYLAMINO)ALANINE; L-TRYPTOPHAN; EOSINOPHILIA-MYALGIA SYNDROME; LEWIS RAT ID PEAK-E; ACID; EMS; 1,1'-ETHYLIDENEBIS(L-TRYPTOPHAN); CONTAMINANTS; SUBSTANCE; FASCIITIS; INGESTION; SAMPLES AB 3-(Phenylamino)alanine (PAA), a newly discovered impurity in case-associated L-tryptophan tablets, has been investigated as a possible contributing factor in the etiology of eosinophilia-myalgia syndrome (EMS). We have studied distribution and elimination of PAA in rats which were administered a single 5 mg/kg dose of PAA by gastric gavage. PAA concentrations in blood, brain, kidney and liver were measured by high-performance liquid chromatography (HPLC) with electrochemical detection. The concentration of PAA in each tissue reached a maximum at 5 h, and then gradually declined. A high level of PAA still remained at 24 h, indicating gradual elimination. The concentration of PAA in brain at 5 h was 2139 ng/g tissue, demonstrating passage through the blood-brain barrier. Consecutive administration of PAA (5 mg/kg) for 4 days resulted in approximately double the concentration in all tissues. Chronic treatment using PAA incorporated into food pellets for 6 weeks resulted in similar accumulations in each tissue, and following 12 days on a PAA free diet, levels of this drug were still detectable in all tissues. C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. RP ADACHI, J (reprint author), KOBE UNIV,SCH MED,DEPT LEGAL MED,CHUO KU,KUSUNOKI CHO,KOBE 650,JAPAN. NR 17 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-5761 J9 ARCH TOXICOL JI Arch. Toxicol. PD FEB PY 1995 VL 69 IS 4 BP 266 EP 270 DI 10.1007/s002040050169 PG 5 WC Toxicology SC Toxicology GA QJ434 UT WOS:A1995QJ43400008 PM 7755488 ER PT J AU CLEVIDENCE, BA REICHMAN, ME JUDD, JT MUESING, RA SCHATZKIN, A SCHAEFER, EJ LI, ZL JENNER, J BROWN, CC SUNKIN, M CAMPBELL, WS TAYLOR, PR AF CLEVIDENCE, BA REICHMAN, ME JUDD, JT MUESING, RA SCHATZKIN, A SCHAEFER, EJ LI, ZL JENNER, J BROWN, CC SUNKIN, M CAMPBELL, WS TAYLOR, PR TI EFFECTS OF ALCOHOL-CONSUMPTION ON LIPOPROTEINS OF PREMENOPAUSAL WOMEN - A CONTROLLED DIET STUDY SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE ALCOHOL; PLASMA LIPIDS; WOMEN; LIPOPROTEINS; APOLIPOPROTEINS ID HIGH-DENSITY-LIPOPROTEIN; CORONARY HEART-DISEASE; APOLIPOPROTEIN-A-I; CHOLESTEROL EFFLUX; BLOOD-PRESSURE; MYOCARDIAL-INFARCTION; TRIGLYCERIDE LEVELS; SERUM-LIPOPROTEINS; MENSTRUAL-CYCLE; BREAST-CANCER AB A substantial portion of American women consume alcohol, but controlled studies of alcohol-induced changes in lipoproteins of women are rare. In this study, the effects of alcohol consumption (equivalent to two drinks per day) on the lipoprotein profiles of 34 premenopausal women were measured while controlling subjects' diet and various other potentially confounding variables including phase of the menstrual cycle. Alcohol and no-alcohol treatments were administered in a crossover design, and blood samples were obtained during the early follicular phase of the third month of treatment. With alcohol, HDL cholesterol levels increased 10%, LDL levels decreased 8%, and levels of lipoprotein(a) were unchanged. The increase in HDL cholesterol was due to an increase in both HDL(2) and HDL(3), and the overall size of HDL particles was increased. HDL particles containing apolipoprotein (ape) A-I and apoA-II as well as those containing apoA-I but no apoA-II were elevated in response to alcohol. Although these observations are limited to a single phase of the menstrual cycle, the alcohol-induced changes in lipoproteins are consistent with changes that are thought to confer protection against coronary heart disease. C1 NCI, DIV CANC PREVENT & CONTROL, CANC PREVENT STUDIES BRANCH, BETHESDA, MD 20892 USA. GEORGE WASHINGTON UNIV, DEPT MED, LIPID RES CLIN, WASHINGTON, DC USA. TUFTS UNIV, USDA, HUMAN NUTR RES CTR AGING, BOSTON, MA 02111 USA. RP CLEVIDENCE, BA (reprint author), USDA ARS, BELTSVILLE AGR RES CTR, BELTSVILLE HUMAN NUTR RES CTR, DIET & HUMAN PERFORMANCE LAB, BELTSVILLE, MD 20705 USA. NR 60 TC 54 Z9 54 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD FEB PY 1995 VL 15 IS 2 BP 179 EP 184 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA QJ017 UT WOS:A1995QJ01700002 PM 7749823 ER PT J AU BENINATI, S NICOLINI, L JAKUS, J PASSEGGIO, A ABBRUZZESE, A AF BENINATI, S NICOLINI, L JAKUS, J PASSEGGIO, A ABBRUZZESE, A TI IDENTIFICATION OF A SUBSTRATE SITE FOR TRANSGLUTAMINASES ON THE HUMAN PROTEIN-SYNTHESIS INITIATION-FACTOR 5A SO BIOCHEMICAL JOURNAL LA English DT Article ID HYPUSINE-CONTAINING PROTEIN; PURIFICATION; POLYAMINES; DEOXYHYPUSINE; SEQUENCE; LIVER AB Protein synthesis initiation factor 5A (eIF-5A) from human erythrocytes was found to be a substrate for both plasma transglutaminase (Factor XIIIa) and guinea pig liver transglutaminase (GPLTG). When purified eIF-5A was incubated with GPLTG or Factor XIIIa in the presence of succinylated beta-casein, a covalent complex was identified. By isolating and analysing the product of the transglutaminases (TGases) reaction, the site of modification on eIF-SA has been identified as the unique amino acid hypusine. The complex beta-casein eIF-5A was enzymically digested with proteinases and the predicted covalent cross-link of gamma-glutamyl-<(omega)over bar>-hypusine was isolated from the digests by ion-exchange chromatography and purified by reversed-phase h.p.l.c. Acid hydrolysis of the purified dipeptide yielded equimolar amounts of hypusine and glutamic acid, Furthermore, fast atom bombardment m.s. analysis confirmed the isomer assignment to be gamma-glutamyl-(omega)over bar>-hypusine. These data indicate that hypusine-50 of the eIF-5A chain functions as acyl acceptor substrate for TGases, and reveal that eIF-5A may be cross-linked to intracellular proteins by TGases, Because the precise function of eIF-5A is still unknown, our results appear particularly stimulating in the light of the recent finding of a new biological role for this protein as a cellular factor binding specifically to the human immunodeficiency virus-1 Rev activation domain [Ruhl, Himmelspach, Bahr, Hammerschmid, Jaksche, WoIff; Auschauer, Farrington, Probst, Bevec and Hauber (1993) J. Cell Biol. 123, 1309-1320]. C1 NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. UNIV NAPLES,DEPT BIOPHYS & BIOCHEM,I-80136 NAPLES,ITALY. RP BENINATI, S (reprint author), UNIV ROMA TOR VERGATA,DEPT BIOL,VIA RIC SCI,I-00133 ROME,ITALY. OI Beninati, Simone/0000-0002-2704-0745 NR 21 TC 27 Z9 27 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD FEB 1 PY 1995 VL 305 BP 725 EP 728 PN 3 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QF437 UT WOS:A1995QF43700006 PM 7848270 ER PT J AU PRUSS, D HAYES, JJ WOLFFE, AP AF PRUSS, D HAYES, JJ WOLFFE, AP TI NUCLEOSOMAL ANATOMY - WHERE ARE THE HISTONES SO BIOESSAYS LA English DT Article ID GLOBULAR DOMAIN; CORE PARTICLE; LINKER DNA; PROTEIN INTERACTIONS; CRYSTAL-STRUCTURE; TERMINAL TAIL; RNA GENE; CHROMATIN; TRANSCRIPTION; RESOLUTION AB The recent surge of discoveries concerning the structural organization of nucleosomes, together with genetic evidence of highly specialized roles for the histones in gene regulation, have brought a renewed need for a detailed understanding of nucleosomal anatomy. Here we review recent structural advances leading to a new level of understanding of the nucleosome and chromatin fibre structure. We discuss the problems and challenges for existing models of chromatin structure and, in particular, consider how linker histones may bind within the nucleosome, together with the implications of their association for the structure of the chromatin fibre. RP PRUSS, D (reprint author), NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892, USA. NR 66 TC 105 Z9 105 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0265-9247 J9 BIOESSAYS JI Bioessays PD FEB PY 1995 VL 17 IS 2 BP 161 EP 170 DI 10.1002/bies.950170211 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA QJ978 UT WOS:A1995QJ97800010 PM 7748166 ER PT J AU LAPPE, M RAUSCHECKER, JP AF LAPPE, M RAUSCHECKER, JP TI MOTION ANISOTROPIES AND HEADING DETECTION SO BIOLOGICAL CYBERNETICS LA English DT Article ID SUPRASYLVIAN VISUAL-CORTEX; OPTICAL-FLOW; MACAQUE MONKEY; SELF-MOTION; CENTRIFUGAL MOTION; NEURAL NETWORK; EYE-MOVEMENTS; EGO-MOTION; FIELD; DIRECTION AB In motion-processing areas of the visual cortex in cats and monkeys, an anisotropic distribution of direction selectivities displays a preference for movements away from the fovea. This 'centrifugal bias' has been hypothetically linked to the processing of optic flow fields generated during forward locomotion. In this paper, we show that flow fields induced on the retina in many natural situations of locomotion of higher mammals are indeed qualitatively centrifugal in structure, even when biologically plausible eye movements to stabilize gaze on environmental targets are performed. We propose a network model of heading detection that carries an anisotropy similar to the one found in cat and monkey. In simulations, this model reproduces a number of psychophysical results of human heading detection. It suggests that a recently reported human disability to correctly identify the direction of heading from optic flow when a certain type of eye movement is simulated might be linked to the noncentrifugal structure of the resulting retinal flow field and to the neurophysiological anisotropies. C1 NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. RP LAPPE, M (reprint author), RUHR UNIV BOCHUM,DEPT ZOOL & NEUROBIOL,UNIV STR 150,D-44780 BOCHUM,GERMANY. RI Rauschecker, Josef/A-4120-2013 NR 58 TC 26 Z9 26 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-1200 J9 BIOL CYBERN JI Biol. Cybern. PD FEB PY 1995 VL 72 IS 3 BP 261 EP 277 DI 10.1007/BF00201489 PG 17 WC Computer Science, Cybernetics; Neurosciences SC Computer Science; Neurosciences & Neurology GA QL645 UT WOS:A1995QL64500007 PM 7703300 ER PT J AU MOONEN, CTW AF MOONEN, CTW TI IMAGING OF HUMAN BRAIN ACTIVATION WITH FUNCTIONAL MRI SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID CORTEX RP MOONEN, CTW (reprint author), NIH,NATL CTR RES RESOURCES,BEPR,IN VIVO NMR RES CTR,BETHESDA,MD 20892, USA. RI Moonen, Chrit/K-4434-2016 OI Moonen, Chrit/0000-0001-5593-3121 NR 7 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiat. PD FEB 1 PY 1995 VL 37 IS 3 BP 141 EP 143 DI 10.1016/0006-3223(94)00260-A PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA QD270 UT WOS:A1995QD27000001 PM 7727621 ER PT J AU HITRI, A CASANOVA, MF KLEINMAN, JE WEINBERGER, DR WYATT, RJ AF HITRI, A CASANOVA, MF KLEINMAN, JE WEINBERGER, DR WYATT, RJ TI AGE-RELATED-CHANGES IN [H-3] GBR-12935 BINDING-SITE DENSITY IN THE PREFRONTAL CORTEX OF CONTROLS AND SCHIZOPHRENICS SO BIOLOGICAL PSYCHIATRY LA English DT Article DE SCHIZOPHRENIA; DOPAMINE TRANSPORTER; AGE; [H-3] GBR 12935; PREFRONTAL CORTEX; BENZTROPINE ID POSITRON EMISSION TOMOGRAPHY; H-3 GBR-12935 BINDING; PARKINSONS-DISEASE; DOPAMINE UPTAKE; HUMAN-BRAIN; RECEPTORS; PHARMACOLOGY; TRANSPORTER; D1 AB We investigated dopamine transporter receptor ligand binding in the prefrontal cortex as a function of age in schizophrenic and control postmortem brains. [H-3]GBR 12935 binding constants were calculated by Scatchard analysis from the autopsied brains from 29 individuals with schizophrenia, and 28 control subjects. There were wide interindividual variations in B-max and K-D that were not related to gender, age, or postmortem interval (PMI) in controls. While there were no significant associations between gender, PMI, and B-max, or K-D in individuals with schizophrenia, there was a significant negative correlation between age and B-max (r = -.44, p .02). The slope of the regression fines between age and B-max for the two groups was significantly different. The results suggest a differential effect of age, or something associated with age, on [H-3]GBR 12935 binding sites in the prefrontal cortex of controls and individuals with schizophrenia. C1 NIMH,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. NIMH,CTR NEUROSCI,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. FU NIMH NIH HHS [MH 31862] NR 32 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiat. PD FEB 1 PY 1995 VL 37 IS 3 BP 175 EP 182 DI 10.1016/0006-3223(94)00202-E PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA QD270 UT WOS:A1995QD27000006 PM 7727626 ER PT J AU RICHARDSON, LL KLEINMAN, HK DYM, M AF RICHARDSON, LL KLEINMAN, HK DYM, M TI BASEMENT-MEMBRANE GENE-EXPRESSION BY SERTOLI AND PERITUBULAR MYOID CELLS IN-VITRO IN THE RAT SO BIOLOGY OF REPRODUCTION LA English DT Article ID GROWTH FACTOR-BETA; EXTRACELLULAR-MATRIX COMPONENTS; HEPARAN-SULFATE PROTEOGLYCAN; MESSENGER-RNA LEVELS; LAMININ VARIANTS; SEMINIFEROUS TUBULE; ANDROGEN CONTROL; SCHWANN-CELLS; BASAL LAMINA; CYCLIC-AMP AB Both Sertoli and myoid cells have been shown to be required for the appropriate deposition of basement membrane in the testis. We sought to define the pattern of basement membrane gene expression in Sertoli and peritubular myoid cells in vitro in order to begin to understand the regulatory mechanisms involved in basement membrane synthesis. Sertoli and myoid cells cultured alone or together were examined for synthesis of basement membrane components. Immunocytochemical localization demonstrated that Sertoli cells alone produced laminin and collagen IV, but not fibronectin, while myoid cells produced all three proteins. In Sertoli:myoid cocultures, a sequential deposition of the components into extracellular fibers was noted during 5 days of culture. Northern blot analysis revealed that mRNA levels for the laminin B1 chain and collagen TV increased from Days 3 to 5 in Sertoli cell monocultures. By contrast, the levels of laminin B1, collagen IV, heparan sulfate proteoglycan, and fibronectin decreased in the cocultures. Transcripts for the laminin A chain were not detected in the myoid cells; instead these cells produced the mRNA for the laminin homologue, merosin. This observation was confirmed by immunolocalization of merosin to the tunica propria of the testis and in cultured myoid cells. These data describe the expression of the basement membrane genes by Sertoli and peritubular myoid cells and provide the basis for future studies to determine the mechanisms that regulate the expression of the basement membrane genes in the testis. C1 GEORGETOWN UNIV,MED CTR,DEPT CELL BIOL,WASHINGTON,DC 20007. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. FU NICHD NIH HHS [HD16260] NR 53 TC 60 Z9 61 U1 2 U2 3 PU SOC STUDY REPRODUCTION PI MADISON PA 1526 JEFFERSON ST, MADISON, WI 53711-2106 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD FEB PY 1995 VL 52 IS 2 BP 320 EP 330 DI 10.1095/biolreprod52.2.320 PG 11 WC Reproductive Biology SC Reproductive Biology GA QD476 UT WOS:A1995QD47600016 PM 7711202 ER PT J AU WHEELER, DL CHRAMBACH, A AF WHEELER, DL CHRAMBACH, A TI COMPUTER-SIMULATION OF THE DIRECTIONAL DISPLACEMENT OF ROD-SHAPED, ARC-SHAPED, AND CIRCULAR OBJECTS IN AN ARRAY OF OBSTACLES, REPRESENTING A SIMPLE-MODEL FOR THE GEL-ELECTROPHORESIS OF SMALL DNA SO BIOPOLYMERS LA English DT Article AB The gel electrophoresis of DNA of identical length but various static conformations was simulated using a two-dimensional model of the movement of rod-shaped, arc-shaped, and circular objects through random arrays of disk-shaped obstacles. Al low obstacle density the displace ment rate of these objects decreases from the rod-shaped to the circular to the ar c-shaped objects. Ar high obstacle densities, the displacement rare of circular objects approaches zero. The alignment of the are-shaped objects along the axis of the directional movement of the objects was less than that achieved by the rod-shaped objects. Rod-shaped and arc-shapen objects were retarded in their movement by collisions with the obstacles, the number of collisions of the former, in view of their greater ability to align, was less than that of the latter Circular objects were exclusively retarded bq collisions, while the arc-shaped objects exhibited an additional retarding mechanism, viz. the suspension (''hanging'') on the obstacles. When the rigid objects were made flexible, their displacement increased. The increase rr as most pronounced with the circular objects, allowing them to penetrate at obstacle densities from which the rigid objects were excluded. (C) 1995 John Wiley & Sons, Inc. RP WHEELER, DL (reprint author), NICHHD,MACROMOLEC ANAL SECT,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892, USA. NR 10 TC 7 Z9 8 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD FEB PY 1995 VL 35 IS 2 BP 179 EP 185 DI 10.1002/bip.360350206 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QE536 UT WOS:A1995QE53600005 PM 7696563 ER PT J AU TSAI, A GALLO, M PETTERSON, T SHILOACH, J AF TSAI, A GALLO, M PETTERSON, T SHILOACH, J TI LARGE-SCALE PRODUCTION AND PURIFICATION OF CLINICAL GRADE PSEUDOMONAS-AERUGINOSA EXOTOXIN-A FROM ESCHERICHIA-COLI SO BIOPROCESS ENGINEERING LA English DT Article ID EPIDERMAL GROWTH-FACTOR; ESCHERICHIA-COLI; MONOCLONAL-ANTIBODY; INVIVO THERAPY; RECEPTOR; IMMUNOTOXINS; EXPRESSION; ONCOGENE; ANTIGENS; RICIN AB Immunotoxin therapy for cancer utilizes hybrid proteins composed of a cell targeting moiety which is a monoclonal antibody reactive with the cancer cell surface, and a cytotoxic agent which is either a bacterial or plant toxin, to specifically attack cancer cells. The immunotoxin B3LysPE38, composed of the modified Pseudomonas aeruginosa exotoxin A (LysPE38) chemically linked to a murine monoclonal antibody (B3), was effective in killing various forms of cancer in mice. To test the therapeutic value in human, a phase I clinical study was designed in which 0.1-1.0 mg of B3LysPE38/Kg of body weight would be administered to each patient. Early estimates of the expected enrolled patient population for this study indicated a need for gram amounts of highly purified immunotoxin. Therefore, a fermentation and purification procedure was developed to isolate 10 grams of LysPE38 (> 99% pure) with clearance levels of pyrogen at 10E.U. and bacterial DNA at 6pg per mg of LysPE38. The high density fermentation process was based on an adaptive control strategy and the purification process was composed of ion exchange and hydrophobic interaction column chromatography. C1 NIDDK,BIOTECHNOL UNIT,LCDB,BETHESDA,MD 20892. NCI,LMB,BETHESDA,MD 20892. PHARM BIOPROC TECHNOL,S-75182 UPPSALA,SWEDEN. NR 24 TC 3 Z9 4 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0178-515X J9 BIOPROCESS ENG JI Bioprocess Eng. PD FEB PY 1995 VL 12 IS 3 BP 115 EP 118 PG 4 WC Biotechnology & Applied Microbiology; Engineering, Chemical SC Biotechnology & Applied Microbiology; Engineering GA QR585 UT WOS:A1995QR58500002 ER PT J AU MERRICK, BA PENCE, PM HE, C PATTERSON, RM SELKIRK, JK AF MERRICK, BA PENCE, PM HE, C PATTERSON, RM SELKIRK, JK TI PHOSPHOR IMAGE-ANALYSIS OF HUMAN P53 PROTEIN ISOFORMS SO BIOTECHNIQUES LA English DT Article ID TUMOR SUPPRESSOR PROTEIN; CELL-LINES; STOICHIOMETRY; ACID AB Phosphor imaging was evaluated for detection, quantitation and resolution of multiphosphorylated protein isoforms separated by two-dimensional gel electrophoresis. A nuclear phosphoprotein, p53, was isolated by immunoprecipitation after biosynthetic labeling with S-35, P-32 or P-33 in cultured human cells. Of the three radionuclides, S-35 was the most sensitive in detection after a 1-week exposure, although shorter exposure times were effective. In dividing cells, 11 S-35-labeled isoforms were found, of which 10 were phosphorylated by P-33 and P-32. Exposure of phosphonuclides for one half-life showed that P-33 radiolabeling produced better resolution among isoforms than P-32 but was less sensitive in detection. Volume integration showed phosphorylated isoforms comprised from 1% to 25% of total isoform signal. The relative phosphorylation of each p53 isoform wa estimated by normalizing P-33 or P-32 isoform volumes with the corresponding S-35 volume and showed progressive phosphorylation of acidic isoforms. Additionally, phosphor imaging capably detected quantitative changes among individual isoforms after experimental modulation of the isoform pattern by serum deprivation. The described electrophoretic isolation and quantitation procedures should find general application in discerning active and inactive phosphoisoforms for eventual identification. RP MERRICK, BA (reprint author), NIEHS,MOLEC CARCINOGENESIS LAB,D4-03,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 27 TC 14 Z9 14 U1 1 U2 1 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD FEB PY 1995 VL 18 IS 2 BP 292 EP 299 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QF438 UT WOS:A1995QF43800025 PM 7727133 ER PT J AU MARLTON, P CLAXTON, DF LIU, P ESTEY, EH BERAN, M LEBEAU, M TESTA, JR COLLINS, FS ROWLEY, JD SICILIANO, MJ AF MARLTON, P CLAXTON, DF LIU, P ESTEY, EH BERAN, M LEBEAU, M TESTA, JR COLLINS, FS ROWLEY, JD SICILIANO, MJ TI MOLECULAR CHARACTERIZATION OF 16P DELETIONS ASSOCIATED WITH INVERSION-16 DEFINES THE CRITICAL FUSION FOR LEUKEMOGENESIS SO BLOOD LA English DT Article ID ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE MYELOMONOCYTIC LEUKEMIA; ACUTE MYELOID-LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; BREAKPOINT CLUSTER REGION; CHROMOSOMAL TRANSLOCATION; GENE; EOSINOPHILS; EXPRESSION; THERAPY AB The inversion of chromosome 16 [inv(16)] in acute myeloid leukemia (AML) is associated with a p-arm deletion in a subset of patients. The inversion results in two fusion genes: 5'-CBFB/MYH11-3' on 16p and 5'-MYH11/CBFB-3' on 16q. We have studied cells from 42 patients with inv(16) (38 patients) or t(16; 16) (four patients) to define the frequency and characteristics of the deletion further. Using fluorescence in situ hybridization (FISH) with probes from cosmids, cosmid contigs, and yeast artificial chromosomes (YACs), we found that six patients with inv(16) had a deletion of between 150 and 350 kb centromeric to the p-arm inversion breakpoint cluster region (p-ibc). This region was shown to contain the 5' portion of the myosin heavy chain (MYH11) gene. YACs containing the p-ibc, which had been useful as FISH probes in the diagnosis of inv(16), detected the inversion in deletion as well as nondeletion patient cells. Thus, the deleted region identified in patients is entirely contained within the human genomic content of the YACs. Southern blot experiments using probes flanking the p-ibc indicated that the deletion removes segments within 10 kb centromeric of the p-ibc. Reverse transcription-polymerase chain reaction (RT-PCR) using primers from the 5' region of CBFB and the 3' region of MYH11 (distal to the p-ibc) produced the 5'-CBFB/MYH11-3' chimeric transcript in inv(16)/del patients. These data confirm that the 5'-CBFB/MYH11-3' chimeric transcript, rather than the reciprocal 5'-MYH11/CBFB-3', is the critical product for chromosome 16-related leukemogenesis. (C) 1995 by The American Society of Hematology. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT MOLEC GENET,HOUSTON,TX 77030. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT HEMATOL,HOUSTON,TX 77030. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. UNIV CHICAGO,PRITZKER SCH MED,DEPT HEMATOL ONCOL,CHICAGO,IL 60637. FOX CHASE CANC CTR,DEPT MED ONCOL,PHILADELPHIA,PA 19111. RI Marlton, Paula/F-3026-2011; Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X FU NCI NIH HHS [CA34936, CA49639, CA55164] NR 26 TC 77 Z9 78 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 FEB 1 PY 1995 VL 85 IS 3 BP 772 EP 779 PG 8 WC Hematology SC Hematology GA QD923 UT WOS:A1995QD92300024 PM 7833479 ER PT J AU HARRIS, NL JAFFE, ES STEIN, H BANKS, PM CHAN, JKC CLEARY, ML DELSOL, G DEWOLFPEETERS, C FALINI, B GATTER, KC GROGAN, TM ISAACSON, PG KNOWLES, DM MASON, DY MULLERHERMELINK, HK PILERI, SA PIRIS, MA RALFKIAER, E WARNKE, RA AF HARRIS, NL JAFFE, ES STEIN, H BANKS, PM CHAN, JKC CLEARY, ML DELSOL, G DEWOLFPEETERS, C FALINI, B GATTER, KC GROGAN, TM ISAACSON, PG KNOWLES, DM MASON, DY MULLERHERMELINK, HK PILERI, SA PIRIS, MA RALFKIAER, E WARNKE, RA TI LYMPHOMA CLASSIFICATION PROPOSAL - CLARIFICATION SO BLOOD LA English DT Letter ID NON-HODGKINS LYMPHOMAS; GROUP EXPERIENCE; CLINICAL-TRIAL; ONCOLOGY GROUP; REPRODUCIBILITY; CANCER C1 NCI, BETHESDA, MD 20892 USA. FREE UNIV BERLIN, KLINIKUM BENJAMIN FRANKLIN, W-1000 BERLIN, GERMANY. UNIV TEXAS, HLTH SCI CTR, SAN ANTONIO, TX USA. QUEEN ELIZABETH HOSP, HONG KONG, HONG KONG. STANFORD UNIV, SCH MED, STANFORD, CA 94305 USA. UNIV TOULOUSE 3, FAC MED PURPAN, F-31062 TOULOUSE, FRANCE. CATHOLIC UNIV LEUVEN, B-3000 LOUVAIN, BELGIUM. UNIV PERUGIA, INST HEMATOL, I-06100 PERUGIA, ITALY. UNIV OXFORD, JOHN RADCLIFFE HOSP, DEPT CELLULAR SCI, OXFORD OX3 9DU, ENGLAND. UNIV ARIZONA, SCH MED, TUCSON, AZ USA. UCL, SCH MED, LONDON W1N 8AA, ENGLAND. CORNELL UNIV, MED CTR, NEW YORK HOSP, NEW YORK, NY 10021 USA. UNIV WURZBURG, W-8700 WURZBURG, GERMANY. UNIV BOLOGNA, BOLOGNA, ITALY. HOSP VIRGEN SALUD, TOLEDO, SPAIN. UNIV COPENHAGEN, HERLEV, DENMARK. RP HARRIS, NL (reprint author), HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT PATHOL, BOSTON, MA USA. NR 14 TC 50 Z9 50 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 1995 VL 85 IS 3 BP 857 EP 860 PG 4 WC Hematology SC Hematology GA QD923 UT WOS:A1995QD92300040 PM 7833492 ER PT J AU LANTOS, TA GORCS, TJ PALKOVITS, M AF LANTOS, TA GORCS, TJ PALKOVITS, M TI IMMUNOHISTOCHEMICAL MAPPING OF NEUROPEPTIDES IN THE PREMAMILLARY REGION OF THE HYPOTHALAMUS IN RATS SO BRAIN RESEARCH REVIEWS LA English DT Review DE POSTERIOR HYPOTHALAMUS; PREMAMILLARY NUCLEUS; TUBEROMAMILLARY NUCLEUS; SUPRAMAMILLARY NUCLEUS; POSTERIOR HYPOTHALAMIC NUCLEUS; ARCUATE NUCLEUS; IMMUNOHISTOCHEMISTRY; NEUROPEPTIDE ID CENTRAL-NERVOUS-SYSTEM; THYROTROPIN-RELEASING-HORMONE; MELANOCYTE-STIMULATING HORMONE; HISTAMINERGIC NEURON SYSTEM; SOMATOSTATIN-CONTAINING NEURONS; GENE-RELATED PEPTIDE; ELECTRON-MICROSCOPIC IMMUNOCYTOCHEMISTRY; HYDROXYLASE-LIKE IMMUNOREACTIVITIES; VASOACTIVE INTESTINAL POLYPEPTIDE; VENTRAL PREMAMMILLARY NUCLEUS AB The topographical distribution of neuropeptide-containing cell bodies, fibers and terminals was studied in the premamillary region of the rat hypothalamus using light microscopic immunohistochemistry. Alternate coronal sections through the posterior third of the hypothalamus of normal and colchicine-treated male rats were immunostained for 19 different neuropeptides and their distributions were mapped throughout the following structures: the ventral and dorsal premamillary, the supramamillary, the tuberomamillary and the posterior hypothalamic nuclei, as well as the premamillary portion of the arcuate nucleus and the postinfundibular median eminence. Seventeen of the investigated neuropeptides were present in neuronal perikarya, nerve fibers and terminals while the gonadotropin associated peptide and vasopressin occurred only in fibers and terminals. Growth hormone-releasing hormone-, somatostatin-, alpha-melanocyte stimulating hormone-, adrenocorticotropin-, beta-endorphin- and neuropeptide Y-immunoreactive neurons were seen exclusively in the premamillary portion of the arcuate nucleus. Thyrotropin-releasing hormone-, dynorphin A- and galanin-containing neurons were distributed mainly in the arcuate and the tuberomamillary nuclei. A high number of methionine- and leucine-enkephalin-immunoreactive cells were detected in the arcuate and dorsal premamillary nuclei, as well as in the area ventrolateral to the fornix. Substance P-immunoreactive perikarya were present in very high number within the entire region, in particular in the ventral and dorsal premamillary nuclei. Cell bodies labelled with cholecystokinin- and calcitonin gene-related peptide antisera were found predominantly in the supramamillary and the terete nuclei, respectively. Corticotropin-releasing hormone-, vasoactive intestinal polypeptide- and neurotensin-immunoreactive neurons were scattered randomly in low number, mostly in the arcuate and the ventral and dorsal premamillary nuclei. Peptidergic fibers were distributed unevenly throughout the whole region, with each peptide showing an individual distribution pattern. The highest density of immunoreactive fibers was presented in the ventral half of the region including the arcuate, the ventral premamillary and the tuberomamillary nuclei. The supramamillary nucleus showed moderately dense fiber networks, while the dorsal premamillary and the posterior hypothalamic nuclei were poor in peptidergic fibers. C1 HUNGARIAN ACAD SCI,UNITED RES ORG,NEUROBIOL LAB,H-1094 BUDAPEST,HUNGARY. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RP LANTOS, TA (reprint author), SEMMELWEIS UNIV MED,SCH MED,NEUROMORPHOL LAB,TUZOLTO U 58,H-1450 BUDAPEST,HUNGARY. RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 NR 220 TC 84 Z9 84 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0173 J9 BRAIN RES REV JI Brain Res. Rev. PD FEB PY 1995 VL 20 IS 2 BP 209 EP 249 DI 10.1016/0165-0173(94)00013-F PG 41 WC Neurosciences SC Neurosciences & Neurology GA QP371 UT WOS:A1995QP37100005 PM 7795657 ER PT J AU TRENT, JM WEBER, B GUAN, XY ZHANG, J COLLINS, F ABEL, K DIAMOND, A MELTZER, P AF TRENT, JM WEBER, B GUAN, XY ZHANG, J COLLINS, F ABEL, K DIAMOND, A MELTZER, P TI MICRODISSECTION AND MICROCLONING OF CHROMOSOMAL ALTERATIONS IN HUMAN BREAST-CANCER SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE CHROMOSOMES; BREAST CANCER; CHROMOSOME MICRODISSECTION; PHYSICAL MAPPING ID MALIGNANT-MELANOMA; RAPID GENERATION; AMPLIFICATION; REGION; PROBES; TRANSLOCATIONS; ABNORMALITIES; CARCINOMAS; ONCOGENE; DISEASE AB The recognition of recurring sites of chromosome changes in malignancies has greatly facilitated the identification of genes implicated in the pathogenesis of human cancers. Based especially upon recent studies [1-4], it appears increasingly likely that a subset of recurring chromosome alterations will be recognized in human breast cancer. Currently recognized chromosome changes characterizing breast carcinoma include the recognition of cytologic features of gene amplification (e.g. double minutes [dmins] and homogeneously staining regions [HSRs]) [5-8]. As these and other chromosome regions are implicated in recurring abnormalities in breast cancer, it will become increasingly important to have band- or region-specific genomic libraries and probes in order to facilitate high resolution physical mapping and ultimately to clone breast cancer related genes [9]. Toward this end an important recent development in physical mapping has been the establishment of chromosome microdissection as a rapid and reproducible approach to rapidly isolate and characterize chromosome region-specific DNA, greatly facilitating the initial steps in positional cloning of disease-related genes [10-13]. In this brief report, we will highlight the application of chromosome microdissection to the generation of region-specific probes for both fluorescent in situ hybridization (FISH) and the generation of genomic microclone libraries. Additionally, efforts using this methodology to generate a microclone library encompassing the early onset breast/ovarian cancer (BRCA1) gene will be presented. C1 UNIV MICHIGAN,DEPT INTERNAL MED,ANN ARBOR,MI 48109. UNIV MICHIGAN,CTR HUMAN GENOME,ANN ARBOR,MI 48109. RP TRENT, JM (reprint author), NIH,NATL CTR GENOME RES,CANC GENET LAB,9000 ROCKVILLE PIKE,BLDG 49 RM 4A22,BETHESDA,MD 20892, USA. RI Guan, Xin-Yuan/A-3639-2009 OI Guan, Xin-Yuan/0000-0002-4485-6017 NR 24 TC 3 Z9 3 U1 1 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD FEB PY 1995 VL 33 IS 2 BP 95 EP 102 DI 10.1007/BF00682717 PG 8 WC Oncology SC Oncology GA QG617 UT WOS:A1995QG61700001 PM 7749145 ER PT J AU SALOMON, DS NORMANNO, N CIARDIELLO, F BRANDT, R SHOYAB, M TODARO, GJ AF SALOMON, DS NORMANNO, N CIARDIELLO, F BRANDT, R SHOYAB, M TODARO, GJ TI THE ROLE OF AMPHIREGULIN IN BREAST-CANCER SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE AMPHIREGULIN; BREAST TUMORS; EGF RECEPTOR; ONCOGENES; STEROID HORMONES; TRANSFORMATION ID GROWTH-FACTOR-ALPHA; MAMMARY EPITHELIAL-CELLS; MESSENGER RIBONUCLEIC-ACID; FACTOR RECEPTOR FAMILY; C-HA-RAS; TGF-ALPHA; EGF-RECEPTOR; ESTROGEN-RECEPTOR; INVITRO TRANSFORMATION; SIGNAL-TRANSDUCTION AB Amphiregulin (AR) is an epidermal growth factor (EGF)-related peptide that operates exclusively through the EGF receptor and that can bind to heparin. AR also possesses nuclear localization sequences in the extended NH2-terminal region suggesting an additional intracellular site of action. AR mRNA and protein expression have been detected in primary human mammary epithelial cell strains, nontransformed human mammary epithelial cell lines, several human breast cancer cell lines, and primary human breast carcinomas. The frequency and levels of AR protein expression are generally higher in invasive breast carcinomas than in ductal carcinomas in situ or in normal, noninvolved mammary epithelium. In addition, AR can function as an autocrine and/or juxtacrine growth factor in human mammary epithelial cells that have been transformed by an activated c-Ha-ras proto-oncogene or by overexpression of c-erb B-2. AR expression is also enhanced by mammotrophic hormones such as estrogens and other growth factors such as EGF. C1 FDN PASCALE,IST NAZL STUDIO & CURA TUMORI,I-80131 NAPLES,ITALY. UNIV NAPLES FEDERICO II,FAC MED & CHIRURG,CATTEDRA ONCOL MED,I-80131 NAPLES,ITALY. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. RP SALOMON, DS (reprint author), NCI,TUMOR IMMUNOL & BIOL LAB,TUMOR GROWTH FACTOR SECT,9000 ROCKVILLE,BETHESDA,MD 20892, USA. OI Ciardiello, Fortunato/0000-0002-3369-4841; Normanno, Nicola/0000-0002-7158-2605 NR 79 TC 46 Z9 47 U1 2 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD FEB PY 1995 VL 33 IS 2 BP 103 EP 114 DI 10.1007/BF00682718 PG 12 WC Oncology SC Oncology GA QG617 UT WOS:A1995QG61700002 PM 7749138 ER PT J AU WEBER, BL ABEL, KJ COUCH, FJ MERAJVER, S CASTILLA, L BRODY, LC COLLINS, FS AF WEBER, BL ABEL, KJ COUCH, FJ MERAJVER, S CASTILLA, L BRODY, LC COLLINS, FS TI TRANSCRIPT IDENTIFICATION IN THE BRCA1 CANDIDATE REGION SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE BRCA1; BREAST OVARIAN CANCER SUSCEPTIBILITY GENE; CDNA; EXON AMPLIFICATION; MOLECULAR CLONING; TUMOR SUPPRESSOR GENE ID BREAST-CANCER; FAMILIAL BREAST; OVARIAN-CANCER; COLORECTAL CANCERS; GENETIC-ANALYSIS; CHROMOSOME-17Q12-Q21; HISTORY; CHROMOSOME-5Q21; RETINOBLASTOMA; MUTATIONS AB Chromosome 17q12-21 is known to contain a gene (or genes) which confers susceptibility to early-onset breast cancer and ovarian cancer (BRCA1). Identification and isolation of BRCA1 will likely provide the basis for increased understanding of the pathogenesis of breast and ovarian cancer, the development of targeted diagnostic and therapeutic approaches, and a means of screening women at risk of being BRCA1 mutation carriers. Genetic and physical maps of the BRCA1 candidate region have been largely completed and efforts are being directed at identification of candidate genes from within this region. We have begun the task of identifying transcripts from this region employing three complementary strategies. These include: 1) direct cDNA screening with cosmids derived from the BRCA1 region; 2) exon amplification; and 3) magnetic bead capture. Transcripts identified using these approaches are being characterized for: 1) tissue expression pattern; 2) the presence of genomic rearrangement in DNA derived from affected members of families believed to show linkage between breast cancer and genetic markers in the BRCA1 candidate interval; 3) altered size and/or expression pattern in RNA prepared from such individuals; and 4) homology to known genes or functional motifs. Germline mutations in affected individuals from these families will serve as presumptive evidence of BRCA1 identity. C1 UNIV MICHIGAN,DEPT INTERNAL MED,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT BIOL,ANN ARBOR,MI 48109. NATL CTR HUMAN GENOME RES,BETHESDA,MD. NR 32 TC 1 Z9 1 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD FEB PY 1995 VL 33 IS 2 BP 115 EP 124 DI 10.1007/BF00682719 PG 10 WC Oncology SC Oncology GA QG617 UT WOS:A1995QG61700003 PM 7749139 ER PT J AU QUARTO, R THOMAS, D LIANG, CT AF QUARTO, R THOMAS, D LIANG, CT TI BONE PROGENITOR-CELL DEFICITS AND THE AGE-ASSOCIATED DECLINE IN BONE REPAIR CAPACITY SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article ID POSTMENOPAUSAL OSTEOPOROSIS; GROWTH-HORMONE; MESSENGER-RNA; RAT; MARROW; INVITRO; ESTROGEN; YOUNG AB Aging bone shows a progressive decline in mass and strength. Previous studies have suggested that bone marrow stem cells are reduced with aging and that this could be responsible, in part, for age-associated bone deficits. We measured the number of osteoprogenitor cells present in the bone marrow from adult and aged rats as well as their ability to differentiate in vitro and to form bone in vivo. We found that the number of adherent colony-forming cells was significantly lower (65%) in marrow cells isolated from aged compared with adult rats. Furthermore, 88% of the colonies obtained from aged rats were alkaline phosphatase (AP) positive, whereas virtually all the colonies from adult rats were positive. The addition of dexamethasone to the culture medium decreased the proliferation of the adherent cells and reduced the number of colonies obtained from both adult and aged bone marrow, all of which were AP positive. No significant differences were found in the expression of certain major bone cell marker genes as a function of donor age. However, dexamethasone treatment increased expression of osteopontin (OP) by fivefold. Adult stromal cells not treated with dexamethasone and implanted subcutaneously in recipient rats exhibited about 10-fold greater formation of bone compared with cells from aged rats. In contrast, dexamethasone-treated cells exhibited high levels of bone formation, irregardless of donor age or the age of the recipient into which the cells were grafted. These studies are consistent with a deficit of osteoprogenitor cells in the bone marrow site as a contributing, perhaps correctable factor in the decline in bone repair and bone mass with age. C1 NIA,GERONTOL RES CTR,BIOL CHEM LAB,BALTIMORE,MD 21224. OI Quarto, Rodolfo/0000-0002-1146-894X NR 27 TC 252 Z9 262 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD FEB PY 1995 VL 56 IS 2 BP 123 EP 129 DI 10.1007/BF00296343 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QE052 UT WOS:A1995QE05200007 PM 7736320 ER PT J AU ZHUANG, ZP MERINO, MJ CHUAQUI, R LIOTTA, LA EMMERTBUCK, MR AF ZHUANG, ZP MERINO, MJ CHUAQUI, R LIOTTA, LA EMMERTBUCK, MR TI IDENTICAL ALLELIC LOSS ON CHROMOSOME 11Q13 IN MICRODISSECTED IN-SITU AND INVASIVE HUMAN BREAST-CANCER SO CANCER RESEARCH LA English DT Note ID TUMOR-SUPPRESSOR GENES; AMPLIFICATION; CARCINOMAS; ONCOGENE AB Human breast carcinoma is thought to develop through progressive stages from atypical hyperplasias to in situ carcinoma and finally to invasive and metastatic cancer. In situ breast carcinoma consists of small, isolated neoplastic foci which cannot be selectively studied by conventional methods. In this study, me used tissue microdissection to examine the loss of heterozygosity (LOH) of chromosome 11q13 in both in situ and invasive lesions of the breast, as compared to normal breast epithelium from the same patients. Forty-one cases of sporadic breast cancer were analyzed. Tissue microdissection allows for procurement and PCR-based analysis of small lesions using either frozen or formalin-fixed, paraffin-embedded tissue sections. LOH on chromosome 11q13 was found in 24 of 36 (67%) of the informative invasive breast cancer cases using two polymorphic DNA markers specific for this region (INT2 and PYGM). Twenty-one of the cases which demonstrated LOH in the invasive tumor also contained in situ carcinoma in the same tissue section. Seventy-one % (15 of 21) of the microdissected in situ lesions showed LOH of chromosome 11q13. Every case (15 of IS) of in situ tumor with LOH showed loss of the same allele in the corresponding invasive tumor cells. The results of this study suggest that a tumor suppressor gene Located on chromosome 11q13 may play an important role in the early stages of development of sporadic human breast cancer. This finding provides molecular genetic support for the hypothesis that invasive breast cancer arises from in situ lesions. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NR 18 TC 119 Z9 123 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 FEB 1 PY 1995 VL 55 IS 3 BP 467 EP 471 PG 5 WC Oncology SC Oncology GA QD717 UT WOS:A1995QD71700003 PM 7834608 ER PT J AU ADAMSON, PC MURPHY, RF GODWIN, KA ULM, EH BALIS, FM AF ADAMSON, PC MURPHY, RF GODWIN, KA ULM, EH BALIS, FM TI PHARMACOKINETICS OF 9-CIS-RETINOIC ACID IN THE RHESUS-MONKEY SO CANCER RESEARCH LA English DT Note ID TRANS-RETINOIC ACID; ACUTE PROMYELOCYTIC LEUKEMIA; THERAPEUTIC ANTICANCER AGENTS; BINDING PROTEIN; CEREBROSPINAL-FLUID; DIFFERENTIATION THERAPY; 13-CIS-RETINOIC ACID; X RECEPTOR; CANCER; PLASMA AB 9-cis-Retinoic acid is a naturally occurring biologically active retinoid capable of binding and transactivating both the retinoic acid receptors and the retinoid X receptors. A study was performed to characterize the pharmacokinetics 9-cis-retinoic acid following i.v. bolus administration in the nonhuman primate. Groups of three animals received i.v. bolus doses of 9-cis-retinoic acid of either 50 or 100 mg/m(2). Blood and cerebrospinal fluid samples for determination of 9-cis-retinoic acid concentration were obtained prior to and 5, 10, 15, 30, 45, 60, 75, 90, 120, 150, 180, 240, 360, and 480 min following drug administration. The plasma drug concentration profile of 9-cis-retinoic acid was consistent with a first-order elimination process, Kith a harmonic mean half-life of 31 min, and a mean clearance of 97 ml/min/m(2). The pharmacokinetics of 9-cis-retinoic acid were Linear over the dose range studied. Plasma concentrations of all-trans-retinoic acid following 9-cis-retinoic acid administration were less than the limit of quantitation (0.1 mu M), suggesting that isomerization to all-trans-retinoic acid is not a major metabolic pathway. In contrast to all-trans-retinoic acid, the elimination of 9-cis-retinoic acid did not appear to be capacity limited (saturable). Previous studies in the Rhesus monkey have shown that repeated dosing with all-trans-retinoic acid leads to a reduction of this saturable component of elimination and results in reduced exposure to drug. These studies, in an animal model highly predictive of humans, suggest that declines in plasma concentrations of 9-cis-retinoic acid as a result of its repeat administration at doses up to 100 mg/m(2) will not occur. C1 LIGAND PHARMACEUT INC,SAN DIEGO,CA 92121. RP ADAMSON, PC (reprint author), NCI,PEDIAT BRANCH,BLDG 10,ROOM 13N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 38 TC 19 Z9 19 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 FEB 1 PY 1995 VL 55 IS 3 BP 482 EP 485 PG 4 WC Oncology SC Oncology GA QD717 UT WOS:A1995QD71700007 PM 7834612 ER PT J AU BIES, J WOLFF, L AF BIES, J WOLFF, L TI ACCELERATION OF APOPTOSIS IN TRANSFORMING GROWTH-FACTOR BETA-1-TREATED M1 CELLS ECTOPICALLY EXPRESSING B-MYB SO CANCER RESEARCH LA English DT Note ID MESSENGER-RNA; A-MYB; C-MYB; PROLIFERATION; ACTIVATION; FAMILY; GENES; BETA AB Inappropriate expression of genes involved in cell proliferation can result in altered regulation of apoptosis, a process of programmed cell death. Since B-myb has recently been implicated in the cell cycle progression we wanted to examine its role in the apoptotic process. For this purpose we used transforming growth factor beta 1 (TGF-beta 1)-treated M1 myeloid leukemia cell lines that continuously express murine B-myb. It was found that in cells overexpressing B-myb, TGF-beta 1-induced apoptosis was accelerated as assessed by cell viability and DNA fragmentation into nucleosomal fragments. A DNA ladder was detected after 24 h of TGF-beta 1 treatment in these cells, whereas it was not detected until after 36 h in the parental M1 cells. It was further determined by Northern blot analysis that this higher sensitivity of B-myb overexpressing clones was not due to a change in the expression of TGF-beta receptor type I or in the kinetics of the regulation of c-myc, c-myb, bcl-2, and/or bac. C1 NCI,GENET LAB,BETHESDA,MD 20892. NR 23 TC 33 Z9 33 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 1995 VL 55 IS 3 BP 501 EP 504 PG 4 WC Oncology SC Oncology GA QD717 UT WOS:A1995QD71700012 PM 7834617 ER PT J AU JANZ, S GAWRISCH, K LESTER, DS AF JANZ, S GAWRISCH, K LESTER, DS TI TRANSLOCATION AND ACTIVATION OF PROTEIN-KINASE-C BY THE PLASMA-CELL TUMOR-PROMOTING ALKANE PRISTANE SO CANCER RESEARCH LA English DT Article ID PROMYELOCYTIC LEUKEMIA-CELLS; HEMATOPOIETIC-CELLS; DIFFERENTIATION; INVITRO; 2,6,10,14-TETRAMETHYLPENTADECANE; EXPRESSION; BILAYERS; ACID; DNA; SPECTROSCOPY AB Pristane (2,6,10,14-tetramethylpentadecane) is a C-19-isoalkane that promotes the development of plasmacytomas in genetically susceptible BALB/c mice. Similarities between the effects of pristane and protein kinase C (PKC)-activating phorbol esters suggested that the tumor promoting activity of pristane might involve the activation of PKC. Here we show that up to 5 mol% of pristane can be homogeneously incorporated into phosphatidylcholine/phosphatidylserine bilayers. Membrane incorporated pristane partially activated PKC and increased phorbol ester binding to the bilayer by more than 50%. Pristane (50 mu M) delivered as an inclusion complex with beta-cyclodextrin to promyelocytic HL-60 leukemia cells induced a partial Long-term translocation of PKC to the cell membrane. This was accompanied by differentiation of HL-60 cells into macrophage-like cells. It is concluded that activation of PKC may comprise an important aspect of the tumor promoting potential of pristane. C1 NIAAA,MEMBRANE BIOCHEM & BIOPHYS LAB,BETHESDA,MD 20892. US FDA,CTR DRUG EVALUAT & RES,DIV RES & TESTING,LAUREL,MD 20708. RP JANZ, S (reprint author), NCI,GENET LAB,BLDG 37,ROOM 2B09,BETHESDA,MD 20892, USA. NR 47 TC 10 Z9 10 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 1995 VL 55 IS 3 BP 518 EP 524 PG 7 WC Oncology SC Oncology GA QD717 UT WOS:A1995QD71700016 PM 7834620 ER PT J AU ARNOLD, JT WILKINSON, BP SHARMA, S STEELE, VE AF ARNOLD, JT WILKINSON, BP SHARMA, S STEELE, VE TI EVALUATION OF CHEMOPREVENTIVE AGENTS IN DIFFERENT MECHANISTIC CLASSES USING A RAT TRACHEAL EPITHELIAL-CELL CULTURE TRANSFORMATION ASSAY SO CANCER RESEARCH LA English DT Article ID CLINICAL-TRIALS; INHIBITION; CANCER AB The rat tracheal epithelial (RTE) cell focus inhibition assay was used to identify potential chemopreventive agents. Ninety-nine agents were evaluated for their ability to inhibit benzo[a]pyrene-induced transformation of RTE cells. Freshly isolated RTE cells were exposed to benzo[a]pyrene alone or in combination with a chemopreventive agent. After 30 days in culture, transformed foci were scored and inhibition was quantitated. in these studies, foci formation was inhibited mainly by agents which modulate the initiation of carcinogenesis by altering drug-metabolizing enzymes, inhibiting the binding of benzo[a]pyrene to DNA, enhancing detoxification of activated carcinogens, or by inducing epithelial cell differentiation. Such agents include antioxidants, free radical scavengers, glutathione S-transferase enhancers, vitamins, retinoids, and sulfhydryl compounds. Agents which inhibit ornithine decarboxylase and arachidonic acid metabolism were not as effective. The RTE assay provides important data for agent selection prior to whole animal-screening assays in the development of chemoprevention drugs. C1 MANTECH ENVIRONM TECHNOL INC,CELLULAR & MOLEC TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. NCI,DIV CANC PREVENT & CONTROL,CHEMOPREVENT BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [N01-CN-95172-06, N01-CN-95172-02, N01-CN-55503-05] NR 31 TC 40 Z9 41 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 1995 VL 55 IS 3 BP 537 EP 543 PG 7 WC Oncology SC Oncology GA QD717 UT WOS:A1995QD71700019 PM 7834622 ER PT J AU GONZALEZ, FJ AF GONZALEZ, FJ TI GENETIC-POLYMORPHISM AND CANCER SUSCEPTIBILITY - 14TH SAPPORO CANCER SEMINAR SO CANCER RESEARCH LA English DT Editorial Material RP GONZALEZ, FJ (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 42 Z9 43 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 1 PY 1995 VL 55 IS 3 BP 710 EP 715 PG 6 WC Oncology SC Oncology GA QD717 UT WOS:A1995QD71700046 PM 7834645 ER PT J AU HIRSCH, J PETRAKOVA, E FEATHER, MS BARNES, CL AF HIRSCH, J PETRAKOVA, E FEATHER, MS BARNES, CL TI THE REACTION OF D-GLUCOSE WITH AMINOGUANIDINE SO CARBOHYDRATE RESEARCH LA English DT Article DE D-GLUCOSE; BROWNING REACTION; MAILLARD REACTION; AMADORI COMPOUND; AMINOGUANIDINE; 1-AMINO-1-DEOXY-2-KETOSE ID MAILLARD REACTION; NONENZYMATIC GLYCOSYLATION; 3-DEOXYGLUCOSONE; INHIBITION; PRODUCTS; LENS AB The reaction of D-glucose with aminoguanidine was examined at pH 7.0 and 37 degrees C (phosphate buffer). Under these conditions, the reaction requires ca. 42 days for 50% of the sugar to react, as measured by the disappearance of D-glucose, and at 60 degrees C al the aminoguanidine had reacted within 72 h. The initial product, a beta-D-glucopyranosyl aminoguanidine (1) was obtained in the crystalline state as the trifluoroacetate salt. Data collected on this compound suggests that, in solution, it is largely a glycosylamine in the beta pyranose form. Acetylation gave a crystalline heptaacetate (2), which, in solution (as evidenced by NMR spectroscopy) exists in two different conformational forms. The crystal structure of the heptaacetate also includes two conformers. Both crystallographically independent molecules are in the normal beta pyranose form, with the acetylated guanyl residue occupying different spatial positions relative to the ring. C1 UNIV MISSOURI,DEPT BIOCHEM,COLUMBIA,MO 65211. NIDDK,BETHESDA,MD 20892. UNIV MISSOURI,DEPT CHEM,COLUMBIA,MO 65211. NR 24 TC 23 Z9 24 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD FEB 1 PY 1995 VL 267 IS 1 BP 17 EP 25 DI 10.1016/0008-6215(94)00285-N PG 9 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA QG633 UT WOS:A1995QG63300002 PM 7697666 ER PT J AU MELNICK, RL KOHN, MC AF MELNICK, RL KOHN, MC TI MECHANISTIC DATA INDICATE THAT 1,3-BUTADIENE IS A HUMAN CARCINOGEN SO CARCINOGENESIS LA English DT Article ID ETHYL-N-NITROSOUREA; SISTER CHROMATID EXCHANGE; B6C3F1 MICE; SPECIES-DIFFERENCES; BUTADIENE MONOXIDE; MUTATIONAL SPECTRA; HPRT LOCUS; EXPOSURE; MOUSE; METABOLITE AB A review of the epidemiological and mechanistic data on 1,3-butadiene indicates that this chemical is a human carcinogen for which the mouse is an appropriate model for assessing human cancer risk. Butadiene is carcinogenic at multiple organ sites in laboratory animals, including the induction of lymphomas in mice, while epidemioiogical studies have consistently found associations between occupational exposure to butadiene and increased mortality from lymphatic and hematopoietic cancers. Activated oncogenes and inactivated tumor suppressor genes in butadiene-induced tumors in mice are analogous to genetic alterations frequently observed in human cancers. Butadiene is metabolized to mutagenic and carcinogenic epoxides in all mammalian species studied, including humans. These metabolites form N7-alkylguanine adducts which have been detected in liver DNA of mice exposed to butadiene and in urine of exposed workers. Increases in hprt mutations were observed in lymphocytes from mice exposed to butadiene and in occupationally exposed humans. The mutational spectra for butadiene and its epoxide metabolites at the hprt locus in mouse lymphocytes are similar to the mutational spectrum of ethylene oxide; all of these chemicals exhibit a high percentage of frameshift mutations. Ethylene oxide, an alkylating agent that also forms an N7-alkylguanine adduct, was recently classified by the International Agency for Research on Cancer as a human carcinogen. Based on these data, we suggest that cancer induction by ethylene oxide and butadiene involve similar molecular mechanisms. C1 NIEHS,QUANTITAT & COMPUTAT BIOL LAB,RES TRIANGLE PK,NC 27709. RP MELNICK, RL (reprint author), NIEHS,ENVIRONM CARCINOGENESIS PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 62 TC 69 Z9 70 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD FEB PY 1995 VL 16 IS 2 BP 157 EP 163 DI 10.1093/carcin/16.2.157 PG 7 WC Oncology SC Oncology GA QH261 UT WOS:A1995QH26100002 PM 7859343 ER PT J AU DUNNICK, JK ELWELL, MR HUFF, J BARRETT, JC AF DUNNICK, JK ELWELL, MR HUFF, J BARRETT, JC TI CHEMICALLY-INDUCED MAMMARY-GLAND CANCER IN THE NATIONAL-TOXICOLOGY-PROGRAMS CARCINOGENESIS BIOASSAY SO CARCINOGENESIS LA English DT Note ID SALMONELLA MUTAGENICITY TESTS; BREAST-CANCER; AMERICAN WOMEN; ETIOLOGY; COLON; RISK AB Incidences of breast cancer change in populations as people migrate from one area of the world to another, suggesting that environmental factors contribute to this disease. There is a continuing effort to identify these environmental factors and the role that exposures to specific chemicals play in this disease. Results from experimental studies show that chemicals identified to cause mammary gland cancer in rodents are frequently mutagenic chemicals, suggesting that genetic damage is an important mechanism for the induction of this cancer. Prevalent classes of chemicals that were identified to cause mammary gland cancer in rodents in studies by the National Toxicology Program include halogenated hydrocarbons, aromatic amino/nitro compounds and epoxide-forming chemicals. Results from these experimental studies will help to elucidate mechanisms and possible causes of breast cancer in humans. RP DUNNICK, JK (reprint author), NIEHS,RES TRIANGLE PK,NC 27514, USA. NR 31 TC 46 Z9 47 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD FEB PY 1995 VL 16 IS 2 BP 173 EP 179 DI 10.1093/carcin/16.2.173 PG 7 WC Oncology SC Oncology GA QH261 UT WOS:A1995QH26100004 PM 7859345 ER PT J AU CORLEY, J HURTUBISE, RJ BOWMAN, ED WESTON, A AF CORLEY, J HURTUBISE, RJ BOWMAN, ED WESTON, A TI SOLID-MATRIX, ROOM-TEMPERATURE PHOSPHORESCENCE IDENTIFICATION AND QUANTITATION OF THE TETRAHYDROTETROLS DERIVED FROM THE ACID-HYDROLYSIS OF BENZO[A]PYRENE-DNA ADDUCTS FROM HUMAN LUNG SO CARCINOGENESIS LA English DT Note ID HYDROCARBON-DNA ADDUCTS; FLUORESCENCE DETECTION; HUMAN-PLACENTA; TETROLS; ASSAY AB A new method, suitable for human biomonitoring, that uses room temperature phosphorescence for the detection of DNA damage by carcinogenic metabolites of polycyclic aromatic hydrocarbons is described. Samples of human lung DNA (1 mg) that had been subjected to immunoaffinity chromatography (anti-benzo[a]pyrene-diol-epoxide deoxyguanosine monoclonal antibodies) were acid hydrolyzed (0.1 N HCl, 90 degrees C, 3 h) and the resulting DNA lung hydrolyzates separated by high performance liquid chromatography. Relevant fractions were combined with a solid matrix support which consisted of a mixture of alpha-cyclodextrin (alpha-CD):NaCl (1:9) or alpha-CD:TINO3: aNO(3) (1:1:8). The dried and powdered sample-matrix material was analyzed by phosphorescence spectroscopy at room temperature. Certain fractions of human lung samples were found to contain materials that yielded phosphorescence spectra that were indistinguishable from those produced when an authentic r-7, t-8, t-9, c-10-tetrahydroxy-7,8,9, 10-tetrahydrobenzo[a]pyrene reference standard was analyzed. The data confirm previous studies that have reported the presence of r-7, t-8 dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene-DNA adducts in human tissues at levels of 1 adduct/l0(7)-10(8) nucleotides. The alpha-cyclodextrin solid matrix, room temperature phosphorescence technique was performed with a commercially available instrument, but is 50 times more sensitive than the synchronous fluorescence spectroscopic technique previously used. C1 UNIV WYOMING, DEPT CHEM, LARAMIE, WY 82071 USA. UNIV IDAHO, DEPT CHEM, MOSCOW, ID 83844 USA. NCI, HUMAN CARCINOGENESIS LAB, BETHESDA, MD 20892 USA. NR 23 TC 21 Z9 21 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD FEB PY 1995 VL 16 IS 2 BP 423 EP 426 DI 10.1093/carcin/16.2.423 PG 4 WC Oncology SC Oncology GA QH261 UT WOS:A1995QH26100037 PM 7859376 ER PT J AU CAPOGROSSI, MC AF CAPOGROSSI, MC TI STIMULATION OF SARCOLEMMAL SODIUM-HYDROGEN EXCHANGE IN CARDIAC MYOCYTES AS A MEDIATOR OF THE POSITIVE INOTROPIC ACTION OF ALPHA(1) ADRENERGIC AGONISTS SO CARDIOVASCULAR RESEARCH LA English DT Note ID PROTEIN-KINASE-C; INTRACELLULAR PH; ADRENOCEPTOR AGONIST; PURKINJE-FIBERS; NA+/H+ EXCHANGE; CYTOSOLIC PH; CA-2+; RESPONSIVENESS; CARDIOMYOCYTES; MYOFILAMENTS RP CAPOGROSSI, MC (reprint author), NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 19 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD FEB PY 1995 VL 29 IS 2 BP 276 EP 277 DI 10.1016/S0008-6363(96)88582-8 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA QH262 UT WOS:A1995QH26200022 PM 7736507 ER PT J AU MURPHY, E AF MURPHY, E TI COMMENTARIES ON THE END OF YEAR EDITORIAL ON THE DEFINITION OF ISCHEMIA IN LAST DECEMBERS ISSUE SO CARDIOVASCULAR RESEARCH LA English DT Editorial Material RP MURPHY, E (reprint author), NIH,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD FEB PY 1995 VL 29 IS 2 BP 283 EP 284 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA QH262 UT WOS:A1995QH26200029 ER PT J AU WILMER, JL LUSTER, MI AF WILMER, JL LUSTER, MI TI CHEMICAL INDUCTION OF INTERLEUKIN-8, A PROINFLAMMATORY CHEMOKINE, IN HUMAN EPIDERMAL KERATINOCYTE CULTURES AND ITS RELATION TO CYTOGENETIC TOXICITY SO CELL BIOLOGY AND TOXICOLOGY LA English DT Article DE INTERLEUKIN-1-ALPHA; TUMOR NECROSIS FACTOR-ALPHA; PHORBOL-13-MYRISTATE-12-ACETATE; CYCLOHEXIMIDE; LIPOPOLYSACCHARIDE; PUROMYCIN; BENZO(A)PYRENE; INFLAMMATION; SISTER CHROMATID EXCHANGES ID TUMOR-NECROSIS-FACTOR; CHINESE-HAMSTER OVARY; SISTER-CHROMATID EXCHANGES; FACTOR-ALPHA; CELL-LINES; CHROMOSOME-ABERRATIONS; PROLIFERATION KINETICS; CYTO-TOXICITY; HELA-CELLS; PROMOTER AB Tumor promoters, proinflammatory cytokines, endotoxins, and protein synthesis inhibitors can modulate cell cycle kinetics of various cell types, stimulate production of reactive oxygen species, and induce keratinocytes to produce interleukin-8 (IL-8) a potent chemotactant for polymorphonuclear neutrophils and T lymphocytes. The aim of this study was to determine whether perturbations of cytogenetic responses correlated with the induction of IL-8 expression Cultures of primary human keratinocytes were grown in serum-free medium with 5 mu mol/L bromodeoxyuridine to label DNA and exposed either to phorbol-13-myristate-12-acetate (PMA) (0.0001-100 ng/ml), cycloheximide (CHX) (0.01-50 mu g) lipopolysaccharide (0.1-100 mu g/ml), tumor necrosis factor-a (TNF alpha) (3.13-50 ng/ml), or interleukin-1 alpha (IL-1 alpha) (1-182 pg/ml). Metaphase chromosome preparations were stained by a fluorescence-plus-Giemsa technique to differentiate sister chromatids. For IL-8 production, keratinocytes were grown to 70% confluency and then exposed to chemicals for 24 h. Immunoreactive IL-8 was quantitated from the supernatants by ELISA. With the exception of benzo(a)pyrene used as a positive control, none of the agents induced sister chromatid exchanges. However, PMA and TNF alpha induced IL-8 production that coincided with significant cell cycle inhibition IL-1 alpha had no effect on cytogenetic endpoints, yet stimulated a 6.3-fold increase in IL-8. CHX inhibited cell cycle progression and mitotic activity at concentrations that were 200 times lower than required for IL-8 induction; however, puromycin (0.31-10 mu g/ml), another protein synthesis inhibitor, did not induce IL-8. At all concentrations tested, TNF alpha reduced the mitotic index by similar to 45%, slowed cell cycle progression by similar to 3.5 h, and induced a flat, albeit large, IL-8 response at concentrations greater than or equal to 12.5 ng/ml. These agent-specific response patterns suggest that induction of IL-8 production is not always the inevitable result of cell cycle perturbations or genetic damage. RP WILMER, JL (reprint author), NIEHS,ENVIRONM IMMUNOL & NEUROBIOL SECT,MD C1-04,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 65 TC 17 Z9 18 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0742-2091 J9 CELL BIOL TOXICOL JI Cell Biol. Toxicol. PD FEB PY 1995 VL 11 IS 1 BP 37 EP 50 PG 14 WC Cell Biology; Toxicology SC Cell Biology; Toxicology GA QT139 UT WOS:A1995QT13900005 PM 7600258 ER PT J AU DENNING, MF DLUGOSZ, AA WILLIAMS, EK SZALLASI, Z BLUMBERG, PM YUSPA, SH AF DENNING, MF DLUGOSZ, AA WILLIAMS, EK SZALLASI, Z BLUMBERG, PM YUSPA, SH TI SPECIFIC PROTEIN-KINASE-C ISOZYMES MEDIATE THE INDUCTION OF KERATINOCYTE DIFFERENTIATION MARKERS BY CALCIUM SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID NONPROMOTING 12-DEOXYPHORBOL 13-ESTERS; CULTURED MURINE KERATINOCYTES; MOUSE EPIDERMAL-CELLS; ESTER TUMOR PROMOTERS; PHORBOL ESTER; SUBCELLULAR-DISTRIBUTION; GENE-EXPRESSION; RBL-2H3 CELLS; HUMAN SKIN; BETA-II AB The maturation of epidermal keratinocytes is a tightly regulated, stepwise process which requires protein kinase C (PKC) activation. We investigated the effect of elevated extracellular Ca2+, a potent differentiation signal which increases cellular sn-1,2-diacylglycerol levels, on the PKC isozyme profile of cultured murine keratinocytes. Five PKC isozymes (alpha, delta, epsilon, xi, and eta) were detected by immunoblotting. During Ca2+-induced differentiation, total cellular PKC alpha decreased, PKC epsilon and eta increased 3-5-fold, and the level of other PKC isozymes was relatively unchanged. PKC alpha underwent a progressive translocation from the soluble to the particulate fraction following elevation of extracellular Ca2+. The kinetics of PKC alpha translocation corresponded with the induction of keratinocyte differentiation markers. Both PKC delta and epsilon were selectively lost from the soluble fraction of keratinocytes exposed to elevated extracellular Ca2+, resulting in an increase in the proportion of these isoforms in the particulate fraction. PKC eta increased in both the soluble and particulate fractions, while PKC xi did not change in amount or distribution during keratinocyte differentiation. Selective down-regulation of PKC isoforms by either 12-deoxyphorbol-13-phenylacetate or bryostatin 1 inhibited Ca2+-induced expression of differentiation markers at doses most specific for the down-regulation of PKC alpha. Taken together, these observations suggest that the induction of keratinocyte differentiation by Ca2+ results in the activation of specific PKC isozymes. C1 NCI,DIV CANC ETIOL,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 57 TC 152 Z9 151 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD FEB PY 1995 VL 6 IS 2 BP 149 EP 157 PG 9 WC Cell Biology SC Cell Biology GA QG301 UT WOS:A1995QG30100006 PM 7756173 ER PT J AU WETSEL, WC AF WETSEL, WC TI IMMORTALIZED HYPOTHALAMIC LUTEINIZING-HORMONE-RELEASING HORMONE (LHRH) NEURONS - A NEW TOOL FOR DISSECTING THE MOLECULAR AND CELLULAR BASIS OF LHRH PHYSIOLOGY SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Review DE LUTEINIZING; HORMONE-RELEASING HORMONE; GENETIC TARGETING; NEURONAL CELL LINES; MIGRATION; MORPHOLOGY; IMPLANTATION; PROHORMONE PROCESSING; COCULTURE; PULSATILE RELEASE; SECRETION; GENE EXPRESSION ID NITRIC-OXIDE SYNTHASE; FOLLICLE-STIMULATING-HORMONE; MEDIAN-EMINENCE; GONADOTROPIN-SECRETION; MESSENGER-RNA; RAT-BRAIN; ADENYLATE-CYCLASE; TRANSGENIC MICE; NEUROPEPTIDE-Y; PREOPTIC AREA AB 1. Two LHRH neuronal cell lines were developed by targeted tumorigenesis of LHRH neurons in vivo. These cell lines (GN and GT-1 cells) represent a homogeneous population of neurons. GT-1 cells have been further subcloned to produce the GT1-1, GT1-3, and GT1-7 cell lines. While considerable information is accumulating about GT-1 cells, very little is currently known about the characteristics and responses of GN cells. 2. By both morphological and biochemical criteria, GT-1 cells are clearly neurons. All GT-1 cells immunostain for LHRH and the levels of prohormone, peptide intermediates, and LHRH in the cells and medium are relatively high. 3. GT-1 cells biosynthesize, process, and secrete LHRH. Processing of pro-LHRH appears to be very similar to that reported for LHRH neurons in vivo. At least four enzymes may be involved in processing the prohormone to LHRH. 4. LHRH neurons are unique among the neurons of the central nervous system because they arise from the olfactory placode and grow back into the preoptic-anterior hypothalamic region of the brain. Once these neurons reach this location, they send their axons to the median eminence. With respect to the immortalized neurons, GN cells were arrested during their transit to the brain. In contrast, GT-1 cells were able to migrate to the preoptic-anterior hypothalamic region but were unable correctly to target their axons to the median eminence. These problems in migration and targeting appear to be due to expression of the simian virus T-antigen. 5. While GT-1 cells are a homogeneous population of neurons, they are amenable to coculture with other types of cells. Coculture experiments currently under way should help not only to reveal some of the molecular and cellular cues that are important for neuronal migration and axonal targeting, but they should also highlight the nature of the cellular interactions which normally occur in situ. 6. GT-1 cells spontaneously secrete LHRH in a pulsatile manner. The interpulse interval for LHRH from these cells is almost identical to that reported for release of LH and LHRH in vivo. GT-1 cells are interconnected by both gap junctions and synapses. The coordination and synchronization of secretion from these cells could occur through these interconnections. by feedback from LHRH itself, and/or by several different compounds that are secreted by these cells. One such compound is nitric oxide. 7. GT-1 cells have Na+, K+, Ca2+, and Cl- channels. Polymerase chain reaction experiments coupled with Southern blotting and electrophysiological recordings reveal that GT-1 cells contain at least five types of Ca2+ channels. R-type Ca2+ channels appear to be the most common type of channel and this channel is activated by phorbol esters in the GT-1 cells. 8. LHRH is secreted from GT-1 cells in response to norepinephrine, dopamine, histamine, GABA (GABA-A agonists), glutamate, nitric oxide, neuropeptide Y, endothelin, prostaglandin E(2), and activin A. Phorbol esters are very potent stimulators of LHRH secretion. Inhibition of LHRH release occurs in response to LHRH, GABA (GABA-B agonists), prolactin, and glucocorticoids. 9. Compared to secretion studies, far fewer agents have been tested for their effects on gene expression. All of the agents which have been tested so far have been found either to repress LHRH gene expression or to have no effect. The agents which have been reported to repress LHRH steady-state mRNA levels include LHRH, prolactin, glucocorticoids, nitric oxide, and phorbol esters. While forskolin stimulates LHRH secretion, it does not appear to have any effect on LHRH mRNA levels. RP WETSEL, WC (reprint author), NATL INST ENVIRONM HLTH,CELLULAR & MOLEC PHARMACOL LAB,POB 12233,BLDG 19-03,RES TRIANGLE PK,NC 27709, USA. NR 175 TC 66 Z9 67 U1 0 U2 3 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD FEB PY 1995 VL 15 IS 1 BP 43 EP 78 DI 10.1007/BF02069558 PG 36 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA RD929 UT WOS:A1995RD92900004 PM 7648609 ER PT J AU TING, CC HARGROVE, ME WANG, J PATEL, AD AF TING, CC HARGROVE, ME WANG, J PATEL, AD TI DIFFERENTIAL REQUIREMENT OF PROTEIN-TYROSINE KINASE AND PROTEIN-KINASE-C IN THE GENERATION OF IL-2-INDUCED LAK CELL AND ALPHA-CD3-INDUCED CD3-AK CELL RESPONSES SO CELLULAR IMMUNOLOGY LA English DT Article ID ACTIVATED KILLER-CELLS; LYMPHOCYTE-T ACTIVATION; SIGNAL TRANSDUCTION; RECEPTOR ACTIVATION; ANTI-T3 ANTIBODY; ANTIGEN RECEPTOR; IL-4 REGULATION; CYTO-TOXICITY; PHOSPHORYLATION; INTERLEUKIN-2 AB This study examined the role of protein tyrosine kinase (PTK) and protein kinase C (PKC) in the signal transduction pathways for lymphocyte activation through IL-BR to generate LAK cells and through TCR-CD3 to generate CD3-AK cells. Two PTK inhibitors [herbimycin A and genistein (PTK-I)] and two PKC inhibitors [calphositin C and staurosporine (PKC-I)] were used in the experiments, It was found that the primary activation pathway through IL-BR was PTK-dependent; that is, generation of both the IL-2-induced proliferative and the cytotoxic responses was completely abrogated by PTK-I and not by PKC-I. Quite different results were obtained with the alpha CD3-induced CD3-AK cell response, First, the alpha CD3-induced proliferation was only partially inhibited by PTK-I or PKC-I alone, Second, generation of CD3-AK cytotoxic response was primarily PKC-dependent; that is, only PKC-I induced significant inhibition, Genistein was found to reduce protein tyrosine phosphorylation in both LAK cells and CD3-AK cells, indicating that CD3-AK cells were also susceptible to PTK-I treatment, Further studies showed that PTK-I and not PKC-I suppressed perforin mRNA expression and N-2-benzyoxycarbonyl-1-lysine thiobeneylester esterase production in LAK cells, and the opposite was true for CD3-AK cells, These results indicate that different pathways were employed in lymphocyte activation through IL-BR and TCR-CD3, The former pathway is primarily PTK-dependent, Activation through TCR-CD3 is a more complex event, Induction of a proliferative response can employ either a PTK- or a PKC-dependent pathway, whereas induction of a cytotoxic response is primarily PKC-dependent. Furthermore, it appears that a PTK-independent pathway exists for the induction of a CD3-AK response and thus suggests that activation of the second messenger PKC may not necessarily be preceded by PTK activation. (C) 1995 Academic Press, Inc. C1 NIDDKD,DIV RENAL CELL BIOL,METAB BRANCH,BETHESDA,MD 20892. RP TING, CC (reprint author), NCI,DIV CANC BIOL DIAG & CTR,OFF DIRECTOR,BLDG 10,ROOM 4B17,BETHESDA,MD 20892, USA. NR 43 TC 11 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD FEB PY 1995 VL 160 IS 2 BP 286 EP 296 DI 10.1016/0008-8749(95)80040-P PG 11 WC Cell Biology; Immunology SC Cell Biology; Immunology GA QH401 UT WOS:A1995QH40100018 PM 7536636 ER PT J AU RYBA, NJP TIRINDELLI, R AF RYBA, NJP TIRINDELLI, R TI CLONING OF A NOVEL GTP-BINDING PROTEIN GAMMA-SUBUNIT AND ITS EXPRESSION IN THE OLFACTORY EPITHELIUM SO CHEMICAL SENSES LA English DT Meeting Abstract C1 UNIV PARMA,IST FISIOL UMANA,I-43100 PARMA,ITALY. NIDR,DEPT IMMUNOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0379-864X J9 CHEM SENSES JI Chem. Senses PD FEB PY 1995 VL 20 IS 1 BP 159 EP 160 PG 2 WC Behavioral Sciences; Food Science & Technology; Neurosciences; Physiology SC Behavioral Sciences; Food Science & Technology; Neurosciences & Neurology; Physiology GA QQ130 UT WOS:A1995QQ13000182 ER PT J AU LENFANT, C AF LENFANT, C TI NHLBI CLINICAL GUIDELINES - ANOTHER LOOK SO CIRCULATION LA English DT Editorial Material RP LENFANT, C (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 1 PY 1995 VL 91 IS 3 BP 617 EP 618 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA QD434 UT WOS:A1995QD43400001 PM 7828283 ER PT J AU VASAN, RS LARSON, MG LEVY, D AF VASAN, RS LARSON, MG LEVY, D TI DETERMINANTS OF ECHOCARDIOGRAPHIC AORTIC ROOT SIZE - THE FRAMINGHAM HEART-STUDY SO CIRCULATION LA English DT Article DE AORTA; ECHOCARDIOGRAPHY; BLOOD PRESSURE ID AGE-RELATED-CHANGES; ISOLATED SYSTOLIC HYPERTENSION; PULSE PRESSURE; CARDIOVASCULAR-DISEASE; THORACIC AORTA; HUMAN ARTERIES; DIMENSIONS; POPULATION; REGURGITATION; DILATATION AB Background Previous studies that evaluated the determinants of aortic root size have not yielded uniform results. We examined the relations of age, height, weight, body surface area, sex, and blood pressure to echocardiographically determined aortic root size in a population-based cohort. Methods and Results The study sample consisted of 1849 men and 2152 women in the Framingham Heart Study and Framingham Offspring Study who were Gee of clinically apparent cardiac disease when echocardiography was performed. Aortic root measurements were made by M-mode echocardiography using a leading-edge-to-leading-edge technique. The relations of age, height, weight, body surface area, and blood pressure variables (contemporary and those obtained 8 years before) to aortic root dimension were examined by use of sex-specific correlations and linear regression analyses. Age, height; weight, and sex emerged as the principal determinants of aortic root dimensions in adults (cumulative R(2)=.2085 in men and .2327 in women). The additional effect of contemporary or previous blood pressure measures was small and revealed direct associations of aortic root dimension with mean arterial and diastolic blood pressures and inverse associations with pulse and systolic blood pressures. Previous blood pressure measurements did not contribute significantly to prediction of aortic root size once contemporary blood pressure variables entered the models. Results of regression analyses using a sex-pooled data set showed that on average, the aortic root measurement in women was 2.4 mm smaller than that of men of comparable age, height, and weight. Logistic regression was used to assess the likelihood of aortic root enlargement according to blood pressure levels. After adjustment for age, height, and weight, the odds ratio of aortic dilation for a 1-SD increment in systolic pressure was 0.70 (95% CI, 0.52 to 0.95) in men and 0.79 (95% CI, 0.60 to 1.04) in women; the odds ratio for a 1-SD increment in diastolic pressure was 1.22 (95% CI, 0.91 to 1.63) in men and 1.33 (95% CI, 1.01 to 1.73) in women. Conclusions Age, height, weight, and sex emerged as the principal determinants of aortic root dimensions. The additional influences of blood pressure measurements were small; direct associations of aortic root dimensions with mean arterial and diastolic blood pressures and inverse associations with pulse and systolic blood pressures were observed. Additional prospective studies are needed to confirm these observations and to assess the impact of aortic root dimensions on the incidence of hypertension. C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA 01701. BETH ISRAEL HOSP,DIV CARDIOL,BOSTON,MA. BETH ISRAEL HOSP,DIV CLIN EPIDEMIOL,BOSTON,MA 02215. BOSTON UNIV,SCH MED,BOSTON,MA 02118. NHLBI,BETHESDA,MD 20892. OI Ramachandran, Vasan/0000-0001-7357-5970 NR 65 TC 182 Z9 186 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 1 PY 1995 VL 91 IS 3 BP 734 EP 740 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA QD434 UT WOS:A1995QD43400019 PM 7828301 ER PT J AU MORALES, DE MCGOWAN, KA GRANT, DS MAHESHWARI, S BHARTIYA, D CID, MC KLEINMAN, HK SCHNAPER, HW AF MORALES, DE MCGOWAN, KA GRANT, DS MAHESHWARI, S BHARTIYA, D CID, MC KLEINMAN, HK SCHNAPER, HW TI ESTROGEN PROMOTES ANGIOGENIC ACTIVITY IN HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS IN-VITRO AND IN A MURINE MODEL SO CIRCULATION LA English DT Article DE ANGIOGENESIS; ENDOTHELIUM; ESTROGEN; CELLS ID FIBROBLAST GROWTH-FACTOR; RECONSTITUTED BASEMENT-MEMBRANE; FUNCTIONALLY AGONADAL WOMEN; POLYSILOXANE VAGINAL RINGS; BREAST-CANCER CELLS; TUMOR ANGIOGENESIS; PLASMINOGEN-ACTIVATOR; REPLACEMENT THERAPY; MATRIX COMPONENTS; BLOOD-VESSELS AB Background Angiogenesis is a critical event in wound healing, tumor growth, and the inflammatory vasculitides. Since women have a higher incidence of many vasculitic diseases, we examined the effects of female sex steroids, particularly estradiol, on human umbilical vein endothelial cell (HUVEC) behavior in vitro and on angiogenesis in vivo. Methods and Results HUVECs were grown in estrogen-free medium before each assay. Exogenous 17 beta-estradiol (1 to 5 nmol/L) increased cell attachment to laminin, types I and IV collagen, and fibronectin, as well as to tissue culture plastic. After a confluent monolayer of cells was ''wounded'' by scraping, estradiol-treated (10(-8) mol/L) cells migrated into the wound three times faster than untreated cells. Cell proliferation on plastic and on laminin increased threefold to fivefold, respectively, in the presence of estradiol. Estradiol also enhanced the ability of HUVECs to organize into tubular networks when plated on a reconstituted basement membrane, Matrigel. Estradiol effects on both the ''wounding'' assay and tube formation were blocked by the specific estrogen receptor antagonist ICI 182,780. Ovariectomy markedly decreased in vivo vascularization of Matrigel plugs coinjected with basic fibroblast growth factor in mice. With estrogen replacement, angiogenesis was increased to the levels observed in nonovariectomized mice. Conclusions These studies demonstrate that, in vitro and in vivo, estradiol enhances endothelial cell activities important in neovascularization and suggest a promoting influence of estrogens on angiogenesis. C1 NORTHWESTERN UNIV,SCH MED,DEPT PEDIAT,CHICAGO,IL 60611. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. HOSP CLIN BARCELONA,DEPT INTERNAL MED,BARCELONA,SPAIN. OI Cid Xutgla, Maria Cinta/0000-0002-4730-0938 FU NHLBI NIH HHS [HL-53918, R01 HL053918] NR 58 TC 321 Z9 329 U1 2 U2 10 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 1 PY 1995 VL 91 IS 3 BP 755 EP 763 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA QD434 UT WOS:A1995QD43400022 PM 7530174 ER PT J AU CANNON, RO PANZA, JA GILLIGAN, DM AF CANNON, RO PANZA, JA GILLIGAN, DM TI SELECTIVE LOSS OF MICROVASCULAR ENDOTHELIAL FUNCTION - REPLY SO CIRCULATION LA English DT Letter ID FOREARM RESISTANCE VESSELS; PORCINE CORONARY-ARTERIES; AGGREGATING PLATELETS; DEPENDENT RELAXATION; HYPERCHOLESTEROLEMIA; VASODILATION C1 VIRGINIA COMMONWEALTH UNIV, MED COLL VIRGINIA, RICHMOND, VA 23298 USA. RP NHLBI, CARDIOL BRANCH, BLDG 10, BETHESDA, MD 20892 USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD FEB 1 PY 1995 VL 91 IS 3 BP 905 EP 906 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA QD434 UT WOS:A1995QD43400041 ER PT J AU YAMAMOTO, ME CUTLER, JA LEE, IM AF YAMAMOTO, ME CUTLER, JA LEE, IM TI INFLUENCE OF BASE-LINE URINARY SODIUM AND CALCIUM LEVELS ON BLOOD-PRESSURE RESPONSE TO CALCIUM SUPPLEMENTATION IN ADULTS WITH HIGH NORMAL BLOOD PRESSURES SO CIRCULATION LA English DT Meeting Abstract C1 UNIV PITTSBURGH,PITTSBURGH,PA. NHLBI,BETHESDA,MD. BRIGHAM & WOMENS HOSP,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 1 PY 1995 VL 91 IS 3 BP 925 EP 925 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA QD434 UT WOS:A1995QD43400068 ER PT J AU BURCHFIEL, CM CURB, JD SHARP, DS RODRIGUEZ, BL YANO, K CHYOU, PH FONG, KO ARAKAKI, R AF BURCHFIEL, CM CURB, JD SHARP, DS RODRIGUEZ, BL YANO, K CHYOU, PH FONG, KO ARAKAKI, R TI CORRELATES OF INSULIN IN ELDERLY MEN - THE HONOLULU HEART PROGRAM SO CIRCULATION LA English DT Meeting Abstract C1 UNIV HAWAII MANOA,HONOLULU,HI. KUAKINI MED CTR,NHLBI,HONOLULU,HI. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 1 PY 1995 VL 91 IS 3 BP 926 EP 926 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA QD434 UT WOS:A1995QD43400074 ER PT J AU COOPER, LS BRYAN, RN SHARRETT, AR CHAMBLESS, LE YOUNGBLOOD, ME HEISS, GX GORDON, DL RUSSELL, WF RAILA, FA ELSTER, A AF COOPER, LS BRYAN, RN SHARRETT, AR CHAMBLESS, LE YOUNGBLOOD, ME HEISS, GX GORDON, DL RUSSELL, WF RAILA, FA ELSTER, A TI BLACK-WHITE DIFFERENCES IN THE PREVALENCE OF MRI-DEFINED CEREBRAL INFARCTION IN THE ATHEROSCLEROSIS RISK IN COMMUNITIES STUDY SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 1 PY 1995 VL 91 IS 3 BP 927 EP 927 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA QD434 UT WOS:A1995QD43400078 ER PT J AU BURCHFIEL, CM REED, DM STRONG, JP SHARP, DS CHYOU, PH RODRIGUEZ, BL AF BURCHFIEL, CM REED, DM STRONG, JP SHARP, DS CHYOU, PH RODRIGUEZ, BL TI SMOKING, FISH CONSUMPTION AND MYOCARDIAL LESIONS AT AUTOPSY SO CIRCULATION LA English DT Meeting Abstract C1 UNIV HAWAII MANOA,KUAKINI MED CTR,NHLBI,HONOLULU,HI. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 1 PY 1995 VL 91 IS 3 BP 935 EP 935 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA QD434 UT WOS:A1995QD43400126 ER PT J AU THOM, TJ AF THOM, TJ TI THE STROKE BELT - MORTALITY SINCE 1920 SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 1 PY 1995 VL 91 IS 3 BP 937 EP 937 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA QD434 UT WOS:A1995QD43400139 ER PT J AU GUDAS, JM KLEIN, RC OKA, M COWAN, KH AF GUDAS, JM KLEIN, RC OKA, M COWAN, KH TI POSTTRANSCRIPTIONAL REGULATION OF THE C-MYB PROTOONCOGENE IN ESTROGEN RECEPTOR-POSITIVE BREAST-CANCER CELLS SO CLINICAL CANCER RESEARCH LA English DT Article ID KINASE MESSENGER-RNA; GENE-EXPRESSION; TRANSCRIPTIONAL ACTIVATION; PROGESTERONE RECEPTORS; BINDING-SITES; LINE MCF-7; SEQUENCE; CDNA; DIFFERENTIATION; PROTOONCOGENE AB We have determined that expression of the c-myb protooncogene is associated with estrogen receptor (ER) status and not with tumor progression in human breast epithelial cells, Analysis of normal, immortalized, nontumorigenic, and tumorigenic mammary epithelial cells showed that only ER(+) tumor cell lines expressed readily detectable levels of c-myb mRNA and a M(r) 75,000 protein that was the same size as the c-myb transcripts and protein products present in hematopoietic cells, In this report we show that c-myb mRNA and protein levels are down-regulated during estrogen withdrawal. A 20-fold increase in c-myb mRNA and protein expression was observed upon addition of beta-estradiol to the culture medium, Nuclear run on transcription analyses showed that c-myb was transcribed at the same rate in the presence and absence of estrogen, suggesting that c-myb mRNA accumulation was regulated at a posttranscriptional level, To provide additional evidence that c-myb mRNA was dependent on ER expression, we examined c-myb mRNA levels in MCF-7 cells selected for resistance to antineoplastic drugs, c-myb expression was decreased only in cell lines that showed concomitant loss of ER expression, Moreover, c-myb mRNA was expressed and modulated by estrogen in ER(-), MDA-MB-231 cells stably transfected with a human ER gene, When considered together, these data indicate that c-myb mRNA levels are regulated by estrogens and further suggest that this proto-oncogene plays a role in the biology of ER(+) breast tumor cells. RP GUDAS, JM (reprint author), NCI,MED BRANCH,DIV CANC TREATMENT,MED BREAST CANC SECT,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 71 TC 25 Z9 25 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB PY 1995 VL 1 IS 2 BP 235 EP 243 PG 9 WC Oncology SC Oncology GA RJ526 UT WOS:A1995RJ52600013 PM 9815978 ER PT J AU CLERICI, M SHEARER, GM AF CLERICI, M SHEARER, GM TI THE T-HELPER CELL SHIFT IN AIDS - SIGNIFICANCE FOR PHARMACOTHERAPY SO CLINICAL IMMUNOTHERAPEUTICS LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; HUMAN MEDULLARY THYMOCYTES; SEROPOSITIVE INDIVIDUALS; CYTOKINE PRODUCTION; IMMUNE-RESPONSE; HIV-INFECTION; INFANTS BORN; SURVIVAL; CHILDREN; TYPE-1 AB We recently postulated that susceptibility to HIV infection and progression of HIV-infected individuals to AIDS is controlled by cytokines that regulate 2 functionally distinct subsets of T helper (T-H) lymphocytes. These subsets are T(H)1, which mainly enhance cell-mediated immunity and are regulated by type 1 cytokines, and T(H)2, which mainly augment antibody production and are regulated by type 2 cytokines. HIV-seronegative individuals exposed to HIV may exhibit strong HIV-specific T cell-mediated immunity, since both HIV-specific T helper and T cytotoxic lymphocytes are activated in the absence of seroconversion and disease. Additionally, during progression of HIV-seropositive individuals to AIDS, a decline is observed in type 1 cytokines as well as an increase in the production of type 2 cytokines by HIV-positive peripheral blood mononuclear cells stimulated in vitro. The type 1 to type 2 switch is predictive for the following clinically relevant events: (a) reduction in CD4+ cell counts; (b) time to diagnosis of AIDS;and (c) time to death. The manipulation of the immune response to induce and strengthen HIV-specific immunity may thus be useful in the management of HIV infection. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RP CLERICI, M (reprint author), UNIV MILAN,CATTEDRA IMMUNOL,VIA VENEZIAN 1,I-20133 MILAN,ITALY. NR 66 TC 3 Z9 3 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1172-7039 J9 CLIN IMMUNOTHER JI Clin. Immunother. PD FEB PY 1995 VL 3 IS 2 BP 95 EP 101 PG 7 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA QG953 UT WOS:A1995QG95300001 ER PT J AU HOLMES, GP CHAPMAN, LE STEWART, JA STRAUS, SE HILLIARD, JK DAVENPORT, DS ADAMS, SR ANDERSON, DC BALK, M BRODERSON, JR BROWN, B BROWN, D BROWN, NA DILLEHAY, D ELSE, J FREEMAN, D FREIFELD, A HEBERLING, RL HERRMANN, K HILLIARD, J HOLMES, G HUERKAMP, M JAAX, J JOHNSON, D KALTER, SS KAUFMAN, A LAUGHLIN, C LEHNER, N LISELLA, FS LOPEZ, CE LOPEZ, C MAHY, B MCCLURE, HM MCKINNEY, RW MCVICAR, J MONATH, T MULLIGAN, D MURPHY, F NAHMIAS, AJ OXMAN, MN PELLETT, PE RICHARDSON, JH SILBERMAN, MS SOIKE, K SOUTHERS, JL WARREN, M WELLS, D WHITLEY, R AF HOLMES, GP CHAPMAN, LE STEWART, JA STRAUS, SE HILLIARD, JK DAVENPORT, DS ADAMS, SR ANDERSON, DC BALK, M BRODERSON, JR BROWN, B BROWN, D BROWN, NA DILLEHAY, D ELSE, J FREEMAN, D FREIFELD, A HEBERLING, RL HERRMANN, K HILLIARD, J HOLMES, G HUERKAMP, M JAAX, J JOHNSON, D KALTER, SS KAUFMAN, A LAUGHLIN, C LEHNER, N LISELLA, FS LOPEZ, CE LOPEZ, C MAHY, B MCCLURE, HM MCKINNEY, RW MCVICAR, J MONATH, T MULLIGAN, D MURPHY, F NAHMIAS, AJ OXMAN, MN PELLETT, PE RICHARDSON, JH SILBERMAN, MS SOIKE, K SOUTHERS, JL WARREN, M WELLS, D WHITLEY, R TI GUIDELINES FOR THE PREVENTION AND TREATMENT OF B-VIRUS INFECTIONS IN EXPOSED PERSONS SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID HERPES-SIMPLEX ENCEPHALITIS; POLYMERASE CHAIN-REACTION; RECURRING GENITAL HERPES; DOT-IMMUNOBINDING ASSAY; ACYCLOVIR TREATMENT; SIMIAE INFECTION; RHESUS MACAQUES; ORAL ACYCLOVIR; BREAST-MILK; ANTIBODIES AB Cercopithecine herpesvirus 1 (B virus), enzootic among monkeys of the genus Macaca, causes minimal morbidity in its natural host, In contrast, human B-virus infection presents as rapidly ascending encephalomyelitis with a fatality rate of similar to 70%. This infection remains an uncommon result of macaque-related injuries, although the increase in the use of macaques for research on simian retrovirus infection and hepatitis has expanded the number of opportunities for human exposure. In response to this situation, Emery University and the Centers for Disease Control and Prevention jointly sponsored a B Virus Working Group to formulate a rational approach to the detection and management of human B-virus infection, The resulting guidelines are presented herein and are based upon information from published cases, unpublished cases managed by working-group members, knowledge of the behavior of herpes simplex virus, and-in the absence of hard data-the collective judgment of the group, Although consensus among the coauthors existed on the major points covered by these guidelines, opinions varied widely regarding specific recommendations. C1 CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,ATLANTA,GA 30333. SCOTT & WHITE MEM HOSP & CLIN,DIV INFECT DIS,TEMPLE,TX. NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. SW FDN BIOMED RES,SAN ANTONIO,TX 78284. MICHIGAN STATE UNIV,KALAMAZOO CTR MED STUDIES,DEPT INFECT DIS,KALAMAZOO,MI. NR 81 TC 88 Z9 90 U1 0 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB PY 1995 VL 20 IS 2 BP 421 EP 439 PG 19 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA QG094 UT WOS:A1995QG09400032 PM 7742451 ER PT J AU WOLFE, EJ CAVACINI, LA POSNER, MR SAMORE, MH SPINO, C KETTER, N TRAPNELL, C HAMMER, S GAMBERTOGLIO, JG AF WOLFE, EJ CAVACINI, LA POSNER, MR SAMORE, MH SPINO, C KETTER, N TRAPNELL, C HAMMER, S GAMBERTOGLIO, JG TI PHARMACOKINETICS OF F105, A HUMAN MONOCLONAL-ANTIBODY FOR THE TREATMENT OF HIV-INFECTION - A PHASE-I STUDY SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA. NIAID,BETHESDA,MD. US FDA,ROCKVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1995 VL 57 IS 2 BP 143 EP 143 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QJ312 UT WOS:A1995QJ31200033 ER PT J AU TRACY, TS ROSENBLUTH, BW WRIGHTON, SA GONZALEZ, FJ KORZEKWA, KR AF TRACY, TS ROSENBLUTH, BW WRIGHTON, SA GONZALEZ, FJ KORZEKWA, KR TI FLURBIPROFEN 4'-HYDROXYLATION BY CYP2C9 SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. ELI LILLY & CO,INDIANAPOLIS,IN 46285. W VIRGINIA UNIV,DEPT BASIC PHARMACEUT SCI,MORGANTOWN,WV. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1995 VL 57 IS 2 BP 152 EP 152 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QJ312 UT WOS:A1995QJ31200068 ER PT J AU PISCITELLI, SC FORREST, A RYAN, N WHITFIELD, L FIGG, WD AF PISCITELLI, SC FORREST, A RYAN, N WHITFIELD, L FIGG, WD TI PHARMACOMETRIC ANALYSIS OF THE ERECT OF FUROSEMIDE (F) ON SURAMIN (S) PKS SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 WARNER LAMBERT PARKE DAVIS,ANN ARBOR,MI 48105. SUNY BUFFALO,BUFFALO,NY 14214. MILLARD FILLMORE HOSP,CLIN PHARMACOKINET LAB,BUFFALO,NY 14209. NCI,BETHESDA,MD 20892. NIHCC,DEPT PHARM,BETHESDA,MD. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1995 VL 57 IS 2 BP 158 EP 158 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QJ312 UT WOS:A1995QJ31200092 ER PT J AU GEORGE, DT PHILLIPS, MJM RAWLINGS, R LINNOILA, M AF GEORGE, DT PHILLIPS, MJM RAWLINGS, R LINNOILA, M TI BUSPIRONE DOES NOT PROMOTE LONG-TERM ABSTINENCE IN ALCOHOLICS SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 NIAAA,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1995 VL 57 IS 2 BP 161 EP 161 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QJ312 UT WOS:A1995QJ31200106 ER PT J AU JACOBSEN, FM COMASDIAZ, L AF JACOBSEN, FM COMASDIAZ, L TI DOSE-SEVERITY RESPONSES TO DIVALPROEX IN BIPOLAR ILLNESSES SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. TRANSCULTURAL MENTAL HLTH INST,WASHINGTON,DC. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1995 VL 57 IS 2 BP 207 EP 207 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QJ312 UT WOS:A1995QJ31200285 ER PT J AU SELWITZ, RH NOWJACKRAYMER, R DRISCOLL, WS LI, SH AF SELWITZ, RH NOWJACKRAYMER, R DRISCOLL, WS LI, SH TI EVALUATION AFTER 4 YEARS OF THE COMBINED USE OF FLUORIDE AND DENTAL SEALANTS SO COMMUNITY DENTISTRY AND ORAL EPIDEMIOLOGY LA English DT Article DE COMMUNITY DENTISTRY; DENTAL CARIES; DENTAL CARIES PREVENTION; FLUORIDES, PIT AND FISSURE SEALANTS ID PROGRAM; AREA AB This study evaluates the caries-preventive potential in permanent teeth of dental sealants when combined with an ongoing, school-based fluoride program. The investigation was designed as a sequential, cross-sectional comparison. Dental caries findings in 1987 for 416 children ages 7-11 and 14-17 who received dental sealants and fluorides were compared with corresponding data derived from 1983 baseline examinations of children who received fluoride therapy only. In addition, sealant retention status was determined. Overall mean DMFS scores in 1987 for children in two age groups combined were 51% lower than in 1983. Also, a surface-specific treatment effect was demonstrated in pit and fissures for both older and younger age groups, The overall proportion of sealants retained on occlusal surfaces of first molars after an average of 2 yr (92%) compared favorably with similar figures cited in the scientific literature. The results of this study suggest that pit and fissure sealants confer additional caries-preventive benefits beyond those of fluoride therapy alone. C1 NIDA,DIV MEDICAT DEV,STAT BIOMETR BRANCH,ROCKVILLE,MD. RP SELWITZ, RH (reprint author), NIDR,EPIDEMIOL & ORAL DIS PREVENT PROGRAM,WESTWOOD BLDG,ROOM 538,5333 WESTBARD AVE,BETHESDA,MD 20892, USA. NR 24 TC 17 Z9 18 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0301-5661 J9 COMMUNITY DENT ORAL JI Community Dentist. Oral Epidemiol. PD FEB PY 1995 VL 23 IS 1 BP 30 EP 35 DI 10.1111/j.1600-0528.1995.tb00194.x PG 6 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA QN035 UT WOS:A1995QN03500006 PM 7774174 ER PT J AU SANDAK, B NUSSINOV, R WOLFSON, HJ AF SANDAK, B NUSSINOV, R WOLFSON, HJ TI AN AUTOMATED COMPUTER VISION AND ROBOTICS-BASED TECHNIQUE FOR 3-D FLEXIBLE BIOMOLECULAR DOCKING AND MATCHING SO COMPUTER APPLICATIONS IN THE BIOSCIENCES LA English DT Article ID HOUGH TRANSFORM; PROTEINS; RECOGNITION; ANTIBODY; LIGANDS; COMPLEX; ANTIGEN; MODELS; IMAGES; MUTANT AB The generation of binding modes between two molecules, also known as molecular docking, is a key problem in rational drug design and biomolecular recognition. Docking a ligand e.g., a drug molecule or a protein molecule, to a protein receptor, involves recognition of molecular surfaces as molecules interact at their surface. Recent studies report that the activity of many molecules induces conformational transitions by 'hinge-bending', which involves movements of relatively rigid parts with respect to each other. In ligand-receptor binding, relative rotational movements of molecular substructures about their common hinges have been observed. For automatically predicting flexible molecular interactions, we adapt a new technique developed in Computer Vision and Robotics for the efficient recognition of partially occluded articulated objects. These type of objects consist of ligid parts which are connected by rotary joints (hinges). Our approach is based on an extension and generalization of the Geometric Hashing and Generalized Hough Transform paradigm for rigid object recognition. Unlike other techniques which match each part individually, our approach exploits forcefully and efficiently enough the fact that the different rigid parts do belong to the same flexible molecule. We show experimental results obtained by an implementation of the algorithm for rigid and flexible docking. While the 'correct', crystal-bound complex is obtained with a small RMSD, additional, predictive 'high scoring' binding modes are generated as well, The diverse applications and implications of this general, powerful tool are discussed. C1 PRI DYNCORP,NCI,FCRF,MATH BIOL LAB,FREDERICK,MD 21712. TEL AVIV UNIV,SACKLER FAC EXACT SCI,SCH MATH SCI,DEPT COMP SCI,IL-69978 TEL AVIV,ISRAEL. TEL AVIV UNIV,FAC MED,SACKLER INST MOLEC MED,IL-69978 TEL AVIV,ISRAEL. RI Wolfson, Haim/A-1837-2011 FU NCI NIH HHS [1-CO-74102] NR 35 TC 43 Z9 42 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0266-7061 J9 COMPUT APPL BIOSCI JI Comput. Appl. Biosci. PD FEB PY 1995 VL 11 IS 1 BP 87 EP 99 PG 13 WC Computer Science, Interdisciplinary Applications SC Computer Science GA QR476 UT WOS:A1995QR47600012 PM 7796279 ER PT J AU LE, SY ZHANG, KZ MAIZEL, JV AF LE, SY ZHANG, KZ MAIZEL, JV TI A METHOD FOR PREDICTING COMMON STRUCTURES OF HOMOLOGOUS RNAS SO COMPUTERS AND BIOMEDICAL RESEARCH LA English DT Article ID SINGLE-STRANDED RNA; SECONDARY STRUCTURES; RIBOSOMAL-RNA; SEQUENCES; ENTEROVIRUSES; RHINOVIRUSES; PARAMETERS; ALGORITHM; STABILITY; FOLDINGS AB We have developed a procedure, composed of a set of computer programs, for predicting common RNA structures of homologous sequences. Given a set of homologous RNAs, these programs perform a multiple sequence alignment, generate a list of possible helical stems that are thermodynamically favored in RNA folding from a selected individual sequence, establish a conserved stem list by inspecting the equivalent base pairings and/or conserved helical stems from the derived alignment of homologous RNAs, and build common RNA secondary structures with the maximum scores (i.e., compensatory base changes and number of base pairs, etc.). The approach is a combination of phylogenetic and thermodynamic methods and has been applied to the prediction of common folding structures of the 5' untranslated regions in a number of positive RNA viruses. (C) 1995 Academic Press, Inc. C1 UNIV WESTERN ONTARIO,DEPT COMP SCI,LONDON,ON N6A 5B7,CANADA. RP LE, SY (reprint author), NCI,DIV CANC BIOL,MATH BIOL LAB,BLDG 469,ROOM 151,FREDERICK,MD 21702, USA. NR 27 TC 7 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0010-4809 J9 COMPUT BIOMED RES JI Comput. Biomed. Res. PD FEB PY 1995 VL 28 IS 1 BP 53 EP 66 DI 10.1006/cbmr.1995.1005 PG 14 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA QZ640 UT WOS:A1995QZ64000005 PM 7542191 ER PT J AU NEWLIN, DB AF NEWLIN, DB TI ADDICTION TO DRUGS - FROM BIOLOGY TO DRUG POLICY - GOLDSTEIN,A SO CONTEMPORARY PSYCHOLOGY LA English DT Book Review RP NEWLIN, DB (reprint author), NIDA,ADDICT RES CTR,BALTIMORE,MD, USA. NR 4 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 FEB PY 1995 VL 40 IS 2 BP 112 EP 113 PG 2 WC Psychology, Multidisciplinary SC Psychology GA QG084 UT WOS:A1995QG08400006 ER PT J AU DAVIS, CE APPLEGATE, WB GORDON, DJ CURTIS, RC MCCORMICK, M AF DAVIS, CE APPLEGATE, WB GORDON, DJ CURTIS, RC MCCORMICK, M TI AN EMPIRICAL-EVALUATION OF THE PLACEBO RUN-IN SO CONTROLLED CLINICAL TRIALS LA English DT Article DE ADHERENCE; CLINICAL TRIALS; PLACEBO; RUN-IN; EDUCATION ID CLINICAL-TRIALS; EFFICIENCY; PERIOD; COST AB A prerandomization placebo run-in period is often used in an attempt to exclude potential clinical trial participants who are likely to be poor adherers. It is assumed that potential participants who are poor adherers during the run-in will be less likely to take medication during the trial. This assumption was tested in the Cholesterol Reduction in Seniors Program (CRISP), by prescribing placebo for a 3-week period, but not using the results of the run-in as an entry criterion. The CRISP study was a pilot study designed to compare the effects on lipids and the safety of two doses of lovastatin and placebo in persons 65 years of age and older. After general entry criteria were satisfied, each participant was prescribed placebo for a 3-week period. At the end of the 3-week period, all participants were randomized to one of the three treatment groups, regardless of their adherence to the placebo. Of the 431 participants in the study, 66 (15%) who took less than 80% of the prescribed placebo or who failed to return their unused placebo pills were classified as poor run-in adherers. Poor run-in adherence was associated with lower educational attainment. At 3 and 6 months of follow-up mean adherence was 89.3% and 83.4% among all participants. Exclusion of poor run-in adherers would have increased these means to 90.9% and 85.5%, respectively. Treatment effect as measured by fall in LDL cholesterol would have increased by 2.9 mg/dl in the 40 mg/day dose group at 3 months of follow-up with the addition of a placebo run-in. We conclude that a placebo run-in would have had little effect on the outcome of the CRISP study and would have substantially increased recruitment difficulties. Lower educated persons were more likely to be excluded by a placebo run-in, but the effect of the run-in on follow-up adherence was stronger in less educated participants. More research about the role of a placebo run-in is needed in order to determine the appropriate role of this method in clinical trials. C1 UNIV TENNESSEE,DEPT PREVENT MED,MEMPHIS,TN. NHLBI,DIV HEART & VASC DIS,LIPID METAB ATHEROGENESIS BRANCH,BETHESDA,MD 20892. RP DAVIS, CE (reprint author), UNIV N CAROLINA,SCH PUBL HLTH,COLLABORAT STUDIES COORDINATING CTR,DEPT BIOSTAT,SUITE 203,CHAPEL HILL,NC 27514, USA. FU NHLBI NIH HHS [U01-HL44298, U01-HL44299, U01-HL44311] NR 9 TC 14 Z9 14 U1 1 U2 1 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD FEB PY 1995 VL 16 IS 1 BP 41 EP 50 DI 10.1016/0197-2456(94)00027-Z PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA QQ515 UT WOS:A1995QQ51500004 PM 7743788 ER PT J AU DOMANSKI, MJ AF DOMANSKI, MJ TI THE EPIDEMIOLOGY OF ATRIAL-FIBRILLATION SO CORONARY ARTERY DISEASE LA English DT Review DE ATRIAL FIBRILLATION; ARRHYTHMIA; EPIDEMIOLOGY ID ACUTE MYOCARDIAL-INFARCTION; SYSTEMIC EMBOLIZATION; ANULAR CALCIUM; FOLLOW-UP; STROKE; POPULATION; PREVALENCE; RISK; COMPLICATIONS; PREVENTION RP DOMANSKI, MJ (reprint author), NHLBI,CLIN TRIALS GRP,BETHESDA,MD 20892, USA. NR 47 TC 18 Z9 20 U1 0 U2 0 PU CURRENT SCIENCE PI PHILADELPHIA PA 400 MARKET STREET,SUITE 750 ATTN:SARAH WHEALEN/SUB MGR, PHILADELPHIA, PA 19106 SN 0954-6928 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD FEB PY 1995 VL 6 IS 2 BP 95 EP 100 DI 10.1097/00019501-199502000-00002 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA QR286 UT WOS:A1995QR28600002 PM 7780625 ER PT J AU COBB, JP CUNNION, RE DANNER, RL AF COBB, JP CUNNION, RE DANNER, RL TI NITRIC-OXIDE SYNTHESIS INHIBITION IN SEPTIC SHOCK - REPLY SO CRITICAL CARE MEDICINE LA English DT Letter ID L-ARGININE; ENDOTOXIC-SHOCK; SEPSIS; SURVIVORS; REVERSAL; MODEL RP COBB, JP (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 17 TC 0 Z9 0 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 FEB PY 1995 VL 23 IS 2 BP 413 EP 414 DI 10.1097/00003246-199502000-00032 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA QG871 UT WOS:A1995QG87100032 ER PT J AU YANG, JH RHIM, JS AF YANG, JH RHIM, JS TI 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN - MOLECULAR MECHANISM OF CARCINOGENESIS AND ITS IMPLICATION IN HUMAN IN-VITRO MODEL SO CRITICAL REVIEWS IN ONCOLOGY/HEMATOLOGY LA English DT Review ID ARYL-HYDROCARBON HYDROXYLASE; MOUSE HEPATOMA-CELLS; HUMAN EPIDERMAL-KERATINOCYTES; SOFT-TISSUE SARCOMAS; CYTOCHROME-P1-450 GENE-TRANSCRIPTION; TRICHLOROPHENOL PROCESS ACCIDENT; NUCLEAR TRANSLOCATOR PROTEIN; DIOXIN-RESPONSIVE ENHANCER; VIRAL HARVEY RAS; AH-RECEPTOR C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. TAEGU CATHOLIC UNIV,SCH MED,DEPT PREVENT MED,TAEGU 705034,SOUTH KOREA. NR 165 TC 7 Z9 8 U1 1 U2 1 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD FEB PY 1995 VL 18 IS 2 BP 111 EP 127 DI 10.1016/1040-8428(94)00125-D PG 17 WC Oncology; Hematology SC Oncology; Hematology GA QL911 UT WOS:A1995QL91100003 PM 7695826 ER PT J AU SCHOEN, TJ WALDBILLIG, RJ SEARCY, G GAUDET, SJ JONES, BE CHADER, GJ MOSHYEDI, P AF SCHOEN, TJ WALDBILLIG, RJ SEARCY, G GAUDET, SJ JONES, BE CHADER, GJ MOSHYEDI, P TI IDENTIFICATION AND PARTIAL CHARACTERIZATION OF A PROTEINASE SPECIFIC FOR INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-3 IN AQUEOUS AND VITREOUS HUMORS SO CURRENT EYE RESEARCH LA English DT Article DE IGF; INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN (IGFBP); IGFBP-3; PROTEINASE; VITREOUS HUMOR; AQUEOUS HUMOR; DIABETES MELLITUS; HUMAN; CATTLE (BOVINE) ID IGF-I; PROTEASE; COMPLEX; SERUM; RECEPTORS; INDUCTION; TISSUES; SURGERY; CELLS AB The ICFs (-I and -II) are normally found in serum and other extracellular fluids complexed to specific binding proteins (IGFBPs), While several IGFBPs have been identified in vitreous and aqueous humors, the major serum carrier of IGE IGFBP-3, is notably absent from these fluids. To determine if this paucity could be due to an IGFBP-3 proteinase (IGFBP-3ase), samples of bovine vitreous or aqueous humor were mixed with serum and incubated at 37 degrees C for 4 h followed by western ligand blotting. In these experiments, a distinct loss of the 46 kDa band representing IGFBP-3 was observed while other bands present at 35, 28 and 25 kDa were unaltered. The IGFBP-3ase activity is temperature sensitive, has a pH optimum of about 8.0 and is inhibited by EDTA. Acid treatment of serum to remove endogenously bound IGF does not affect the specificity or activity of the IGFBP-3 proteinase. Size exclusion chromatography of bovine aqueous indicates an approximate molecular weight of 260 kDa. Incubation of recombinant IGFBP-3 or serum with partially-purified IGFBP-3ase results in the appearance of low molecular weight fragments of approximately 30 kDa. These fragments are undetectable by western ligand blotting but are readily visualized using an IGFBP-3 specific antibody. Comparison of normal and diabetic vitreous humor reveals the presence of an increased amount of IGFBP-3 proteolytic fragments in the diabetic as compared to control. These findings indicate the presence of a IGFBP-3 proteinase in aqueous and vitreous humors that may be important in regulating ocular homeostasis. C1 NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. NR 30 TC 8 Z9 8 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD FEB PY 1995 VL 14 IS 2 BP 127 EP 135 DI 10.3109/02713689508999924 PG 9 WC Ophthalmology SC Ophthalmology GA QK624 UT WOS:A1995QK62400007 PM 7539353 ER PT J AU COLE, NB LIPPINCOTTSCHWARTZ, J AF COLE, NB LIPPINCOTTSCHWARTZ, J TI ORGANIZATION OF ORGANELLES AND MEMBRANE TRAFFIC BY MICROTUBULES SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID INTESTINAL EPITHELIAL-CELLS; ENDOCYTIC CARRIER VESICLES; DARBY CANINE KIDNEY; GOLGI-COMPLEX; CYTOPLASMIC DYNEIN; LATE ENDOSOMES; ENDOPLASMIC-RETICULUM; PLASMA-MEMBRANE; FUSION INVITRO; BREFELDIN-A AB Organelles of the central membrane system of higher eukaryotes have been shown to utilize microtubules both for maintenance of their characteristic spatial distributions and for efficient transport of their protein and lipid to diverse sites within the cell. Recent work addressing the mechanisms that underlie this organization provides new insights regarding the roles of microtubules and microtubule motors in influencing organelle dynamics and specific membrane traffic routes through the cytoplasm. RP COLE, NB (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. NR 76 TC 270 Z9 281 U1 3 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 FEB PY 1995 VL 7 IS 1 BP 55 EP 64 DI 10.1016/0955-0674(95)80045-X PG 10 WC Cell Biology SC Cell Biology GA QE873 UT WOS:A1995QE87300009 PM 7755990 ER PT J AU ARNOLD, E DING, JP HUGHES, SH HOSTOMSKY, Z AF ARNOLD, E DING, JP HUGHES, SH HOSTOMSKY, Z TI STRUCTURES OF DNA AND RNA-POLYMERASES AND THEIR INTERACTIONS WITH NUCLEIC-ACID SUBSTRATES SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-1 REVERSE-TRANSCRIPTASE; RIBONUCLEASE-H DOMAIN; I KLENOW FRAGMENT; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; KINETIC MECHANISM; TERNARY COMPLEXES; FIDELITY; IDENTIFICATION AB DNA and RNA polymerases are enzymes that are primarily responsible for copying genetic material in all living systems. The four polymerases whose structures have been determined by X-ray crystallographic methods have significant similarities at the polymerase active site that are indicative of common requirements for polynucleotide synthesis. Structural studies of complexes of the Klenow fragment of Escherichia coli DNA polymerase I, HIV type 1 reverse transcriptase, and rat DNA polymerase beta with DNA are leading to generalized models for catalysis. C1 RUTGERS STATE UNIV,DEPT CHEM,PISCATAWAY,NJ 08854. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. AGOURON PHARMACEUT INC,SAN DIEGO,CA 92121. RP ARNOLD, E (reprint author), RUTGERS STATE UNIV,CTR ADV BIOTECHNOL & MED,679 HOES LANE,PISCATAWAY,NJ 08854, USA. FU NIAID NIH HHS [AI33380, AI27690, AI36144] NR 79 TC 66 Z9 67 U1 0 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD FEB PY 1995 VL 5 IS 1 BP 27 EP 38 DI 10.1016/0959-440X(95)80006-M PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QL448 UT WOS:A1995QL44800005 PM 7539708 ER PT J AU PTITSYN, OB AF PTITSYN, OB TI STRUCTURES OF FOLDING INTERMEDIATES SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Article ID MOLTEN GLOBULE STATE; CYTOCHROME-C; BETA-SHEET; PROTEIN; MECHANISM; CONFORMATION; STABILITY; PATHWAY AB The past year has yielded important results in the study of protein-folding intermediates. It has been shown that the equilibrium molten globule has a native-like tertiary fold and is separated from the unfolded state by a first-order phase transition. New equilibrium intermediates have been revealed and substantial progress has been made in the understanding of two main barriers in protein folding. C1 NCI,MATH BIOL LAB,BETHESDA,MD 20892. RP PTITSYN, OB (reprint author), INST PROT RES,PUSHCHINO 142292,RUSSIA. NR 52 TC 204 Z9 206 U1 0 U2 4 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD FEB PY 1995 VL 5 IS 1 BP 74 EP 78 DI 10.1016/0959-440X(95)80011-O PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QL448 UT WOS:A1995QL44800010 PM 7773749 ER PT J AU DANSKYULLMANN, C SALGALLER, M ADAMS, S SCHLOM, J GREINER, JW AF DANSKYULLMANN, C SALGALLER, M ADAMS, S SCHLOM, J GREINER, JW TI SYNERGISTIC EFFECTS OF IL-6 AND IFN-GAMMA ON CARCINOEMBRYONIC ANTIGEN (CEA) AND HLA EXPRESSION BY HUMAN COLORECTAL-CARCINOMA CELLS - ROLE FOR ENDOGENOUS IFN-BETA SO CYTOKINE LA English DT Article DE INTERFERON-GAMMA; INTERLEUKIN 6; CARCINOEMBRYONIC ANTIGEN; COLON CANCER ID TUMOR-INFILTRATING LYMPHOCYTES; REGULATORY FACTOR-I; INTERFERON-GAMMA; MONOCLONAL-ANTIBODIES; TRANSCRIPTION FACTOR; GROWTH-INHIBITION; COLON-CARCINOMA; REDUCED TUMORIGENICITY; ANTITUMOR-ACTIVITY; ALPHA-INTERFERON AB When administered as single agents, both interferon gamma (IFN-gamma) and interleukin 6 (IL-6) significantly increase carcinoembryonic antigen (CEA) and HLA class I antigen expression on the surface of human colorectal tumour cells, Studies were carried out to determine whether by combining those cytokines a synergistic enhancement of CEA and HLA expression could result, The findings revealed that the administration of 20 units IFN-gamma along with 1.7 ng IL-6, concentrations of each cytokine that individually induced minimal antigenic changes, together synergistically increased CEA and HLA class I as well as induced qualitative changes in HLA expression on WiDr human colon carcinoma cells, The magnitude of the synergistic increases in CEA and HLA class I expression were reminiscent of the level of antigen augmentation observed when administering 20- to 100-fold higher amounts of each cytokine as a single agent. Also, the addition of IL-6 potentiated the IFN-gamma induction of HLA class II expression, The combined administration of IL-6 potentiated the IFN-gamma did not have any additive or synergistic effects on the growth suppression of those tumour cells, Interestingly, utilization of specific neutralizing antibodies for type I interferons abrogated the increases of CEA and HLA expression seen with IL-6 treatment alone or in combination with IFN-gamma. Moreover, reverse transcriptase/polymerase chain reaction analyses revealed a constitutive expression as well as a temporal increase of IFN-beta mRNA transcripts in colon tumour cells treated with IL-6. Therefore, the findings provide indirect evidence that IFN-beta production seems to play a critical role in the ability of IL-6 to upregulate antigen expression alone or in combination with IFN-gamma. These findings provide insight into cytokine combinations that synergistically upregulate tumour-associated and normal HLA antigen expression on the surface of human tumour cells, Those results provide the rationale for the combined use of such cytokines to heighten tumour cell recognition in monoclonal antibody- or cell-mediated-based immunotherapeutic approaches. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT TRANSFUS MED,HLA LAB,BETHESDA,MD 20892. NR 66 TC 45 Z9 45 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4666 J9 CYTOKINE JI Cytokine PD FEB PY 1995 VL 7 IS 2 BP 118 EP 129 DI 10.1006/cyto.1995.1016 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA QK806 UT WOS:A1995QK80600004 PM 7780031 ER PT J AU SORENSEN, UBS AF SORENSEN, UBS TI PNEUMOCOCCAL POLYSACCHARIDE ANTIGENS - CAPSULES AND C-POLYSACCHARIDE - AN IMMUNOCHEMICAL STUDY SO DANISH MEDICAL BULLETIN LA English DT Review ID LINKED-IMMUNOSORBENT-ASSAY; CELL-WALL POLYSACCHARIDE; GROUP-B STREPTOCOCCUS; TEICHOIC-ACID; MONOCLONAL-ANTIBODY; SURFACE COMPONENTS; BACTERIAL DISEASES; LIPOTEICHOIC ACID; BETA-LIPOPROTEIN; COVALENT LINKAGE C1 STATENS SERUM INST,DEPT BACTERIOL,DIV DIAGNOST MICROBIOL,COPENHAGEN,DENMARK. NIH,DEV & MOLEC IMMUN LAB,BETHESDA,MD. NR 112 TC 8 Z9 8 U1 0 U2 3 PU DANISH MEDICAL ASSN PI COPENHAGEN PA TRONDHJEMSGADE 9, DK-2100 COPENHAGEN, DENMARK SN 0011-6092 J9 DAN MED BULL JI Dan. Med. Bull. PD FEB PY 1995 VL 42 IS 1 BP 47 EP 53 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA QJ806 UT WOS:A1995QJ80600004 PM 7729169 ER PT J AU TOYAMA, R OCONNELL, ML WRIGHT, CVE KUEHN, MR DAWID, IB AF TOYAMA, R OCONNELL, ML WRIGHT, CVE KUEHN, MR DAWID, IB TI NODAL INDUCES ECTOPIC GOOSECOID AND LIM1 EXPRESSION AND AXIS DUPLICATION IN ZEBRAFISH SO DEVELOPMENT LA English DT Article DE NODAL; GOOSECOID; LIM1; AXIS DUPLICATION; GENE EXPRESSION; ZEBRAFISH; DANIO ID XENOPUS-EMBRYOS; SPEMANN ORGANIZER; CELL MOVEMENTS; ACTIVIN-A; BODY AXIS; TGF-BETA; FATE MAP; GENE; MESODERM; INDUCTION AB One of the first intercellular signalling events in the vertebrate embryo leads to mesoderm formation and axis determination. In the mouse, a gene encoding a new member of the TGF-beta superfamily, nodal, is disrupted in a mutant deficient in mesoderm formation (Zhou et al., 1993, Nature 361, 543). nodal mRNA is found in prestreak mouse embryos, consistent with a role in the development of the dorsal axis. To examine the biological activities of nodal, we have studied the action of this factor in eliciting axis determination in the zebrafish, Danio rerio. Injection of nodal mRNA into zebrafish embryos caused the formation of ectopic axes that included notochord and somites. Axis duplication was preceded by the generation of an apparent ectopic shield (organizer equivalent) in nodal-injected embryos, as indicated by the appearance of a region over-expressing gsc and lim1; isolation and expression in the shield of the lim1 gene is reported here. These results suggest a role for a nodal-like factor in pattern formation in zebrafish. C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. VANDERBILT UNIV,DEPT CELL BIOL,NASHVILLE,TN 37252. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RI Kuehn, Michael/A-4573-2014 OI Kuehn, Michael/0000-0002-7703-9160 NR 54 TC 139 Z9 140 U1 1 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD FEB PY 1995 VL 121 IS 2 BP 383 EP 391 PG 9 WC Developmental Biology SC Developmental Biology GA QK896 UT WOS:A1995QK89600011 PM 7768180 ER PT J AU NELSON, RG KNOWLER, WC PETTITT, DJ HANSON, RL BENNETT, PH AF NELSON, RG KNOWLER, WC PETTITT, DJ HANSON, RL BENNETT, PH TI INCIDENCE AND DETERMINANTS OF ELEVATED URINARY ALBUMIN EXCRETION IN PIMA-INDIANS WITH NIDDM SO DIABETES CARE LA English DT Article ID DEPENDENT DIABETES-MELLITUS; STAGE RENAL-DISEASE; BLOOD-PRESSURE; NEPHROPATHY; MICROALBUMINURIA; PROTEINURIA; RISK; RETINOPATHY; PREVALENCE; MORTALITY AB OBJECTIVE- To examine the incidence and determinants of elevated urinary albumin excretion in Pima Indians with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN IND METHODS- The incidence of elevated urinary albumin excretion (greater than or equal to 30 mg albumin/g creatinine) and its relationship with baseline characteristics was determined in 456 Pima Indians greater than or equal to 15 years old with NIDDM who were followed for up to 11.6 years (median 4.7 years). RESULTS- Of these 456 subjects, 192 (42%; 58 men, 134 women) developed elevated urinary albumin excretion, 172 of whom (90%) were within the microalbuminuric range (30-299 mg/g). The incidence of elevated urinary albumin excretion was related to retinopathy, type of diabetes treatment, longer duration of diabetes, lower body mass index, and higher values of mean arterial pressure, HbA,, and fasting and 2-h postload plasma glucose concentration at the baseline examination, but not to sex. A relationship with cholesterol was found in durations of diabetes of greater than or equal to 10 years. The cumulative incidence of elevated albumin excretion was 17% after 5 years of NIDDM. CONCLUSIONS- The incidence of elevated urinary albumin excretion in Pima Indians with NIDDM is at least as high as that reported previously in insulin-dependent diabetes mellitus, and its major determinants are the same as those shown previously to predict the development of more advanced renal disease in this population. C1 CLEVELAND CLIN FDN,DEPT BIOSTAT & EPIDEMIOL,CLEVELAND,OH 44195. NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,PHOENIX,AZ. RI Nelson, Robert/B-1470-2012; Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU NIDDK NIH HHS [N01-DK-6-2285] NR 36 TC 70 Z9 71 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 1995 VL 18 IS 2 BP 182 EP 187 DI 10.2337/diacare.18.2.182 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QE300 UT WOS:A1995QE30000005 PM 7729295 ER PT J AU GARDNER, TW KLEIN, R MOSS, SE FERRIS, FL REMALEY, NA AF GARDNER, TW KLEIN, R MOSS, SE FERRIS, FL REMALEY, NA TI DIGOXIN DOES NOT ACCELERATE PROGRESSION OF DIABETIC-RETINOPATHY SO DIABETES CARE LA English DT Note ID SODIUM-POTASSIUM-ATPASE; 4-YEAR INCIDENCE; DIAGNOSIS; AGE; PREVALENCE; RISK; LESS AB OBJECTIVE- To test the hypothesis that digoxin, an inhibitor of Na+-K+-ATPase activity, accelerates the progression of diabetic retinopathy. RESEARCH DESIGN AND METHODS- We compared the incidence and risk of retinopathy in 120 digoxin-taking vs. 867 non-digoxin-taking diabetic participants in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) and in 117 digoxin-taking vs. 1,883 non-digoxin-taking diabetic subjects in the Early Treatment Diabetic Retinopathy Study (ETDRS). In both studies, retinopathy was detected by grading stereoscopic color photographs using the modified Airlie House classification scheme, and a two-step difference in baseline retinopathy grade was considered significant. RESULTS- After controlling for other risk factors, we found no statistically significant association with either dr-year incidence of retinopathy (WESDR) or progression of retinopathy (WESDR and ETDRS) in patients laking digoxin at baseline compared with those not taking digoxin. CONCLUSIONS- These data suggest that digoxin therapy does not adversely affect the course of diabetic retinopathy. C1 PENN STATE UNIV,COLL MED,DEPT OPHTHALMOL,HERSHEY,PA. UNIV WISCONSIN,SCH MED,DEPT OPHTHALMOL,MADISON,WI 53706. NEI,BETHESDA,MD 20892. OI Gardner, Thomas/0000-0002-5112-5810 FU NEI NIH HHS [EY-03083, K11-EY-00331] NR 15 TC 0 Z9 0 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD FEB PY 1995 VL 18 IS 2 BP 237 EP 240 DI 10.2337/diacare.18.2.237 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QE300 UT WOS:A1995QE30000015 PM 7729304 ER PT J AU NAGI, DK KNOWLER, WC CHARLES, MA LIU, QZ HANSON, RL MCCANCE, DR PETTITT, DJ BENNETT, PH AF NAGI, DK KNOWLER, WC CHARLES, MA LIU, QZ HANSON, RL MCCANCE, DR PETTITT, DJ BENNETT, PH TI EARLY AND LATE INSULIN-RESPONSE AS PREDICTORS OF NIDDM IN PIMA-INDIANS WITH IMPAIRED GLUCOSE-TOLERANCE SO DIABETOLOGIA LA English DT Article DE IMPAIRED GLUCOSE TOLERANCE; INSULIN RESPONSE; CHOLESTEROL ID DEPENDENT DIABETES-MELLITUS; FOLLOW-UP; NATURAL-HISTORY; PREVALENCE; ROCHESTER; MINNESOTA; RISK AB Risk factors predicting deterioration to diabetes mellitus were examined in 181 subjects with impaired glucose tolerance. Fifty-seven subjects had impaired glucose tolerance on one occasion followed by normal glucose tolerance at a repeat oral glucose tolerance test, and 124 subjects had impaired glucose tolerance on two successive oral glucose tolerance tests. Subjects were followed for a median period of 5.0 years (range 1.0-17.2). The age- and sex-adjusted cumulative incidence of diabetes at 10 years of follow-up was higher in subjects who had impaired glucose tolerance on both tests (70%) than in those whose glucose tolerance was normal at the repeat test (53%), [rate ratio (RR) = 1.6, 95% confidence intervals (CI) = 1.0-2.5]. Proportional hazards analyses were used to identify baseline risk factors (measured at the repeat oral glucose tolerance test) for subsequent diabetes, and incidence rate ratios were calculated for the 90th percentile compared with the 10th percentile of each continuous variable for the whole group. In all subjects, in separate models, higher body mass index [RR = 2.0, 95% CI = 2.2-9.9], high fasting serum insulin concentrations [RR = 2.4, 95% CI = 1.4-4.2], and low early insulin response [RR = 0.5, 95% CI = 0.3-0.8] 30 min after a glucose load were significant predictors for deterioration to diabetes. In a multivariate analysis which controlled for age and sex, 120-min post-load glucose, fasting insulin and late insulin response predicted diabetes. In subgroup analyses the predictors of diabetes were generally similar in subjects who had impaired glucose tolerance at only one test and those who had impaired glucose tolerance on both tests. These findings suggest that in those subjects with impaired glucose tolerance whose glucose tolerance has returned to normal, the risk of subsequent diabetes is high. Insulin resistance, impaired early insulin response, or both, are predictive of subsequent development of diabetes in Pima Indians with impaired glucose tolerance. C1 NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,DIABET & ARTHRIT EPIDEMIOL SECT,PHOENIX,AZ. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 27 TC 23 Z9 26 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD FEB PY 1995 VL 38 IS 2 BP 187 EP 192 DI 10.1007/BF00400093 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QE494 UT WOS:A1995QE49400008 PM 7713313 ER PT J AU MCCANCE, DR HANSON, RL PETTITT, DJ JACOBSSON, LTH BENNETT, PH BISHOP, DT KNOWLER, WC AF MCCANCE, DR HANSON, RL PETTITT, DJ JACOBSSON, LTH BENNETT, PH BISHOP, DT KNOWLER, WC TI DIABETIC NEPHROPATHY - A RISK FACTOR FOR DIABETES-MELLITUS IN OFFSPRING SO DIABETOLOGIA LA English DT Article DE FAMILIAL AGGREGATION; DIABETES MELLITUS; NEPHROPATHY ID PIMA-INDIANS; RENAL-DISEASE; PROTEINURIA; PREVALENCE; OBESITY AB Both non-insulin-dependent diabetes mellitus and diabetic nephropathy show familial aggregation. If diabetes and renal disease have independent determinants (genetic or otherwise), offspring of parents with diabetic renal disease should have a similar risk of diabetes to those offspring of parents with diabetes alone. To test this hypothesis, the prevalence of diabetes was examined in a population-based pedigree study in Pima Indian offspring of three mutually exclusive parental types: 1) diabetic with renal disease, 2) diabetic, but without renal disease and 3) non-diabetic. Among offspring of one diabetic parent and one non-diabetic parent (n = 320) the prevalence of diabetes at ages 15-24 years and 25-34 years was 0% and 11%, respectively if the diabetic parent did not have renal disease compared with 6% and 28% respectively if the diabetic parent did have renal disease. Corresponding rates for offspring of two diabetic parents (n = 121) were 10% and 17%, respectively if neither parent had renal disease compared with 30% and 50%, respectively if one parent did have renal disease. The presence of renal disease in a parent with diabetes relative to diabetes alone was associated with 2.5 times the odds of diabetes (95% confidence interval 1.4-4.3) in the offspring controlled for age, age at onset of parental diabetes and diabetes in the other parent using logistic regression. These findings provide support for parental diabetic renal disease, independent of age at onset of parental diabetes, conferring an increased risk for diabetes in the offspring. The results are compatible with the hypothesis that the susceptibility to renal disease in the parents and to diabetes in the offspring are due to shared familial environmental factors or to the same gene or set of genes. C1 NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,DIABET & ARTHRIT EPIDEMIOL SECT,PHOENIX,AZ. MALMO GEN HOSP,DEPT RHEUMATOL,S-21401 MALMO,SWEDEN. IMPERIAL CANC RES FUND,LEEDS,W YORKSHIRE,ENGLAND. RP MCCANCE, DR (reprint author), ROYAL VICTORIA HOSP,SIR GEORGE E CLARK METAB UNIT,GROSVENOR RD,BELFAST BT12 6BA,ANTRIM,NORTH IRELAND. RI Hanson, Robert/O-3238-2015; OI Hanson, Robert/0000-0002-4252-7068; Bishop, Tim/0000-0002-8752-8785 FU NCRR NIH HHS [1 P41 RR03655] NR 22 TC 39 Z9 39 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD FEB PY 1995 VL 38 IS 2 BP 221 EP 226 DI 10.1007/BF00400098 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QE494 UT WOS:A1995QE49400013 PM 7713318 ER PT J AU ABATI, A FETSCH, PA AF ABATI, A FETSCH, PA TI OV632 AS A POSSIBLE MARKER FOR MALIGNANT MESOTHELIOMA - HIGH EXPECTATIONS - LOW SPECIFICITY SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Letter RP ABATI, A (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 5 Z9 5 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 FEB PY 1995 VL 12 IS 1 BP 81 EP 82 DI 10.1002/dc.2840120119 PG 2 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA QE646 UT WOS:A1995QE64600017 PM 7789255 ER PT J AU BURT, DW DEY, BR PATON, IR MORRICE, DR LAW, AS AF BURT, DW DEY, BR PATON, IR MORRICE, DR LAW, AS TI THE CHICKEN TRANSFORMING GROWTH FACTOR-BETA-3 GENE - GENOMIC STRUCTURE, TRANSCRIPTIONAL ANALYSIS, AND CHROMOSOMAL LOCATION SO DNA AND CELL BIOLOGY LA English DT Article ID MESSENGER-RNA; FACTOR-BETA; SEQUENCE; CLONING; EXPRESSION; PROMOTER; PRECURSOR; REGION; GROWTH-FACTOR-BETA-2; POLYADENYLYLATION AB In this paper, we report the isolation, characterization, and mapping of the chicken transforming growth factor-beta 3 (TGF-beta 3) gene. The gene contains seven exons and six introns spanning 16-kb of the chicken genome. A comparison of the 5'-flanking regions of human and chicken TGF-beta 3 genes reveals two regions of sequence conservation. The first contains ATF/CRE and TBP/TATA sequence motifs within an 87-bp region. The second is a 162-bp region with no known sequence motifs. Identification of transcription start sites using chicken RNA isolated from various embryonic and adult tissues reveals two sites of initiation, P1 and P2, which map to these two conserved regions. Comparison of 3'-flanking regions of chicken and mammalian TGF-beta 3 genes also revealed conserved sequences, The most significant homologies were found in the 3'-most end of the transcribed region. DNA sequence analysis of chicken TGF-beta 3 cDNAs isolated by 3'-RACE revealed multiple polyadenylation sites unusually distant from a poly(A) signal motif. A Mse I restriction fragment length polymorphism (RFLP) marker was used to map the TGFB3 locus to linkage group E7 on the East Lansing reference backcross. Linkage to the TH locus showed that the TGFB3 locus was physically located on chicken chromosome 5. C1 NCI,METAB BRANCH,BETHESDA,MD 20892. RP BURT, DW (reprint author), ROSLIN INST EDINBURGH,DIV MOLEC BIOL,ROSLIN EH25 9PS,MIDLOTHIAN,SCOTLAND. NR 49 TC 22 Z9 23 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD FEB PY 1995 VL 14 IS 2 BP 111 EP 123 DI 10.1089/dna.1995.14.111 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA QJ276 UT WOS:A1995QJ27600003 PM 7865129 ER PT J AU BOYD, MR PAULI, KD AF BOYD, MR PAULI, KD TI SOME PRACTICAL CONSIDERATIONS AND APPLICATIONS OF THE NATIONAL-CANCER-INSTITUTE IN-VITRO ANTICANCER DRUG DISCOVERY SCREEN SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE ANTINEOPLASTICS; CANCER; DRUG DEVELOPMENT ID TUMOR-CELL-LINES; BREAST CARCINOMA; DIVERSE PANEL; SPONGISTATIN-1; ESTABLISHMENT; TUBULIN; ORIGIN; AGENTS; ASSAY AB During 1985-1990 the U.S. National Cancer Institute (NCl) phased out its murine leukemia P388 anticancer drug screening program and developed as the replacement a new in vitro primary screen based upon a diverse panel of human tumor cell lines. For each substance tested, the screen generates a remarkably reproducible and characteristic profile of differential in vitro cellular sensitivity, or lack thereof, across the 60 different cell lines comprising the panel. Several investigational approaches to display, analysis, and interpretation of such profiles and databases, derived from the testing of tens of thousands of substances during the past 4-5 years since the NCl screen became fully operational, have been explored. A variety of useful, practical applications of the in vitro screen have become apparent. As these applications continue to evolve, they are proving to be complementary to diverse other anticancer screening and drug discovery strategies being developed or pursued elsewhere. Reviewed herein are some practical considerations and selected specific examples, particularly illustrating research applications of the NCl screen that may be more broadly applicable to the search for new anticancer drug development leads with novel profiles of antitumor activity and/or mechanisms of action. (C) 1995 Wiley-Liss, Inc. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,INFORMAT TECHNOL BRANCH,BETHESDA,MD 20892. RP BOYD, MR (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702, USA. NR 44 TC 1114 Z9 1120 U1 4 U2 33 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD FEB PY 1995 VL 34 IS 2 BP 91 EP 109 DI 10.1002/ddr.430340203 PG 19 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QK041 UT WOS:A1995QK04100002 ER PT J AU HAMEL, E BLOKHIN, AV NAGLE, DG YOO, HD GERWICK, WH AF HAMEL, E BLOKHIN, AV NAGLE, DG YOO, HD GERWICK, WH TI LIMITATIONS IN THE USE OF TUBULIN POLYMERIZATION ASSAYS AS A SCREEN FOR THE IDENTIFICATION OF NEW ANTIMITOTIC AGENTS - THE POTENT MARINE NATURAL PRODUCT CURACIN-A AS AN EXAMPLE SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE COLCHICINE; MICROTUBULE-ASSOCIATED PROTEINS; MARINE CYANOBACTERIA; LYNGBYA MAJUSCULA ID MICROTUBULE-ASSOCIATED PROTEINS; GUANOSINE 5'-TRIPHOSPHATE HYDROLYSIS; ASSEMBLY INVITRO; ORGANIC-ACIDS; PHOMOPSIN-A; ANALOGS; TAXOL; DOLASTATIN-10; NUCLEOTIDES; INHIBITION AB Curacin A is a newly isolated lipid natural product that binds in the colchicine site of tubulin and inhibits mitosis. We have examined its effects on tubulin polymerization, studied by turbidimetry, under three reaction conditions. In 1.0 M glutamate + 1.0 mM MgCl2, with a 37 degrees C reaction temperature, we could find no concentration of curacin A that completely inhibited polymerization. A maximal inhibitory effect on turbidity development (about 50%) was observed with 5 mu M drug. Higher drug concentrations induced an abnormal polymerization reaction, which at 40 mu M differed little from the control reaction except for slightly delayed depolymerization in response to reducing the temperature to 0 degrees C. in 0.8 M glutamate (no MgCl2), with a 30 degrees C reaction temperature, complete inhibition did occur at 3-5 mu M drug, but higher drug concentrations again induced an abnormal polymerization reaction. With 40 mu M curacin A this reaction was also similar to the control reaction, except that cold-induced depolymerization was slightly enhanced relative to the control. When polymerization was induced by microtubule-associated proteins, maximal inhibition of turbidity development (about 70%) occurred with 2 mu M drug, with higher curacin A concentrations inducing abnormal polymerization reactions that reached about 60% of the control turbidity readings. Under all three reaction conditions the polymer induced by high concentrations of curacin A consisted of large aggregates of tightly coiled spiral fibers that had a 2-3 filament substructure. The implications of these findings with curacin A are discussed in terms of the use of tubulin polymerization assays as a screen for identifying new antimitotic drugs. (C) 1995 Wiley-Fiss, Inc. C1 OREGON STATE UNIV,COLL PHARM,CORVALLIS,OR 97331. RP HAMEL, E (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BLDG 37,ROOM 5C25,BETHESDA,MD 20892, USA. NR 36 TC 28 Z9 28 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD FEB PY 1995 VL 34 IS 2 BP 110 EP 120 DI 10.1002/ddr.430340204 PG 11 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QK041 UT WOS:A1995QK04100003 ER PT J AU GRIFFIN, RJ BURKA, LT AF GRIFFIN, RJ BURKA, LT TI METABOLISM AND ELIMINATION OF OXAZEPAM IN F344 RATS SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID CHROMATOGRAPHY-MASS-SPECTROMETRY; PHARMACOKINETICS; DIAZEPAM; MICE; DISPOSITION; LORAZEPAM; URINE; LIVER AB The antianxiety agent, oxazepam, is a mouse liver carcinogen as determined by a National Toxicology Program bioassay. An equivalent study in the F344 rat is currently in progress. In an effort to gain insight into whether the mouse or rat will be a better model for human risk assessment, extensive comparative metabolism studies have been conducted in both rodent species and compared with the human literature. In this study, male rats were treated with 25, 250, or 500 mg/kg of radiolabeled oxazepam. In addition, sex comparisons were made at 500 mg/kg after 0 and 14 days of 2500 ppm oxazepam in the feed to mimic bioassay conditions. Similar studies have already been conducted in mice. Recovery of administered activity was dose-dependent, with recovery approaching 100% at the low dose. In all groups, the order of importance of route of elimination was fecal > urinary > expired. No significant sex-dependent differences were detected. Oxidative metabolism and sulfate conjugation were the major routes of metabolism Pretreatment of animals with oxazepam-dosed feed resulted in evidence of hepatic enzyme induction. The rate of elimination for all three routes of elimination was elevated by dosed feed treatment, With regard to metabolite profile and routes of elimination, the rat is less like a human than the mouse. C1 NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. NR 28 TC 5 Z9 5 U1 0 U2 0 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 FEB PY 1995 VL 23 IS 2 BP 232 EP 239 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QF727 UT WOS:A1995QF72700013 PM 7736917 ER PT J AU ANGLADE, E WHITCUP, SM AF ANGLADE, E WHITCUP, SM TI THE DIAGNOSIS AND MANAGEMENT OF UVEITIS SO DRUGS LA English DT Article ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; INTRAOCULAR INFLAMMATORY DISEASE; SYMPATHETIC OPHTHALMIA; BEHCETS-DISEASE; S-ANTIGEN; SYSTEMIC ASSOCIATIONS; RHEUMATOID-ARTHRITIS; CONTROLLED TRIAL; LYMPHOCYTES-T; DOUBLE-BLIND AB The diagnosis and management of uveitis is complicated and challenging, The protean signs and symptoms seen in patients with uveitis may lead to a diagnostic dilemma. A carefully taken history with particular attention to demographic factors and meticulous physical examination are crucial to guiding diagnostic testing, Tailoring the diagnostic approach in patients with uveitis frequently yields useful data in contrast to blanketing every possible uveitic entity, It is also important to distinguish among various aetiologies, including infectious and neoplastic causes which may respond to specific therapy. Medical treatment of noninfectious uveitis must have clear objectives including reduction of inflammation, relief of symptoms and restoration of visual functioning. Familiarity with possible symptoms and signs of adverse drug reactions is essential early in the course of treatment so that their effects may be minimised, Appropriate therapy of presumed autoimmune uveitis is based on disease severity, presence or absence of bilateral disease and the health status of the patient. RP ANGLADE, E (reprint author), NEI,IMMUNOL LAB,BLDG 10,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 77 TC 19 Z9 23 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PD FEB PY 1995 VL 49 IS 2 BP 213 EP 223 DI 10.2165/00003495-199549020-00006 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA QD997 UT WOS:A1995QD99700006 PM 7729329 ER PT J AU LUEDERS, KK AF LUEDERS, KK TI MULTILOCUS GENOMIC MAPPING WITH INTRACISTERNAL A-PARTICLE PROVIRAL OLIGONUCLEOTIDE PROBES HYBRIDIZED TO MOUSE DNA IN DRIED AGAROSE GELS SO ELECTROPHORESIS LA English DT Article DE IAP; MULTILOCUS; MAPPING; HYPOMETHYLATION ID RECOMBINANT INBRED STRAINS; LINKAGE; IDENTIFICATION AB Recently, oligonucleotide probes that detect intracisternal A-particle (IAP) gene subfamilies with a limited number of proviral copies have been shown to be useful multilocus markers. A procedure for hybridization of these probes has been developed and is described. In summary, the main features of the method are the following: (i) A pulse controller is used during agarose gel electrophoresis to improve resolution of restriction fragments in genomic DNA. (ii) Hybridization is performed in a dried gel. (iii) The hybridized gel is washed in tetramethylammonium chloride to eliminate differences in oligonucleotide composition on hybrid stability. Use of the prodecure is demonstrated by genomic mapping of IAP loci in the AXE BXA recombinant inbred mouse strains, identification of hypomethylated loci in tumor cells, and detection of a transposed IAP provirus previously identified as the basis for a mutation at the agouti locus. RP LUEDERS, KK (reprint author), NCI,BIOCHEM LAB,BLDG 37,RM 4C-03,BETHESDA,MD 20892, USA. NR 23 TC 1 Z9 1 U1 0 U2 1 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD FEB PY 1995 VL 16 IS 2 BP 179 EP 185 DI 10.1002/elps.1150160132 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA QN221 UT WOS:A1995QN22100005 PM 7774558 ER PT J AU SUN, B HURSH, DA JACKSON, D BEACHY, PA AF SUN, B HURSH, DA JACKSON, D BEACHY, PA TI ULTRABITHORAX PROTEIN IS NECESSARY BUT NOT SUFFICIENT FOR FULL ACTIVATION OF DECAPENTAPLEGIC EXPRESSION IN THE VISCERAL MESODERM SO EMBO JOURNAL LA English DT Article DE DECAPENTAPLEGIC; DEVELOPMENT; DROSOPHILA; EXTRADENTICLE; ULTRABITHORAX ID DNA-SEQUENCE RECOGNITION; HOMEOTIC GENE-EXPRESSION; DROSOPHILA EMBRYOS; FUNCTIONAL SPECIFICITY; FUSHI-TARAZU; HOMEODOMAIN PROTEINS; BINDING SPECIFICITY; GERM LAYERS; TRANSCRIPTION; ANTENNAPEDIA AB To elucidate the mechanisms by which homeotic selector (HOM) genes specify the unique features of Drosophila segments, we have analyzed the regulation of decapentaplegic (dpp), a transforming growth factor (TGF)-beta superfamily member, and have found that the Ultrabithorax (Ubx) HOM protein directly activates dpp expression in parasegment 7 (PS7) of the embryonic visceral mesoderm. Other factors are also required, including one that appears to act through homeodomain protein binding sites and may be encoded by extradenticle (exd). The exd protein binds in a highly co-operative manner to regulatory sequences mediating PS7-specific dpp expression, consistent with a genetic requirement for exd function in normal visceral mesoderm expression of dpp. A second mechanism contributing to PS7 expression of dpp appears not to require Ubx protein directly, and involves a general visceral mesoderm enhancer coupled to a spatially specific repression element. Thus, even in an apparently simple case where visceral mesoderm expression of the dpp target gene mirrors that of the Ubx HOM protein, full activation by Ubx protein requires at least one additional factor. In addition, a distinct regulatory mode not directly involving Ubx protein also appears to contribute to PS7-specific expression. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MOLEC BIOL & GENET,HOWARD HUGHES MED INST,BALTIMORE,MD 21205. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 63 TC 72 Z9 74 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD FEB 1 PY 1995 VL 14 IS 3 BP 520 EP 535 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QF718 UT WOS:A1995QF71800012 PM 7859741 ER PT J AU CHEN, NY CHEN, WY BELLUSH, L YANG, CW STRIKER, LJ STRIKER, GE KOPCHICK, JJ AF CHEN, NY CHEN, WY BELLUSH, L YANG, CW STRIKER, LJ STRIKER, GE KOPCHICK, JJ TI EFFECTS OF STREPTOZOTOCIN TREATMENT IN GROWTH-HORMONE (GH) AND GH ANTAGONIST TRANSGENIC MICE SO ENDOCRINOLOGY LA English DT Article ID DIABETES-MELLITUS; VASCULAR-DISEASE; INSULIN-LIKE; FACTOR-I; CELLS; EXPRESSION; RECEPTORS; GLOMERULOSCLEROSIS; TISSUE; GENE AB To investigate GH's role in diabetic end organ damage, experimental diabetes was induced with streptozotocin (STZ) in bovine GH (bGH) or bGH antagonist transgenic mice and in their nontransgenic (NTG) litter mates. Body growth, blood glucose, serum insulin-like growth factor-I levels, liver GH receptor (GHR) binding, and kidney histology of these animals were evaluated. After administration of multiple low doses of STZ, 90% of the mice developed hyperglycemia. The diabetic animals, especially those expressing GH and GH antagonist transgenes, demonstrated retarded body growth and reduced insulin-like growth factor-I levels when compared with their nondiabetic litter mates. Kidney histology revealed severe glomerulosclerosis in diabetic and nondiabetic bGH transgenic mice. Diabetic NTG mice exhibited moderate kidney lesions. Diabetic bGH antagonist transgenic mice possessed normal glomeruli indistinguishable from those seen in nondiabetic NTG mice. GHR-binding assays revealed that liver GHR-binding sites were significantly reduced in diabetic NTG mice and transgenic dwarf mice when compared with their nondiabetic controls. Conversely, liver GHR-binding ability was significantly increased in bGH transgenic mice as compared with their NTG littermates and remained high during diabetes. It is concluded that transgenic mice that express a GH antagonist are protected from diabetes and or GH-induced nephropathy. C1 OHIO UNIV, DEPT BIOL SCI, MOLEC & CELLULAR BIOL PROGRAM, ATHENS, OH 45701 USA. OHIO UNIV, EDISON BIOTECHNOL INST, ATHENS, OH 45701 USA. NIDDKD, METAB DIS BRANCH, RENAL CELL BIOL SECT, BETHESDA, MD USA. FU PHS HHS [42137-01AZ] NR 37 TC 95 Z9 95 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 1995 VL 136 IS 2 BP 660 EP 667 DI 10.1210/en.136.2.660 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QD586 UT WOS:A1995QD58600038 PM 7835300 ER PT J AU LEE, CY RECHLER, MM AF LEE, CY RECHLER, MM TI A MAJOR PORTION OF THE 150-KILODALTON INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN (IGFBP) COMPLEX IN ADULT-RAT SERUM CONTAINS UNOCCUPIED, PROTEOLYTICALLY NICKED IGFBP-3 THAT BINDS IGF-II PREFERENTIALLY SO ENDOCRINOLOGY LA English DT Article ID MANNOSE 6-PHOSPHATE RECEPTOR; ACID-LABILE SUBUNIT; PREGNANCY SERUM; CARRIER PROTEINS; HORMONE; HYPOGLYCEMIA; SPECIFICITY; LIGAND; LYMPH; CELLS AB Insulin-like growth factor-II (IGF-II) binds to 150-kilodalton (kDa) protein complexes in adult rat serum that have higher affinity for IGF-II than IGF-I. We now examine the nature of these IGF-II-preferring complexes. A 150-kDa pool, isolated after neutral Sephadex G-200 gel filtration of adult rat serum, bound IGF-II with similar to 80-fold greater affinity than IGF-I, but did not contain immunoprecipitable IGF-II/mannose-6-phosphate receptors, which bind IGF-II with the same preferential affinity. Exogenous IGF-II bound to the 15O-kDa complex without displacing endogenous IGF-I, indicating that it bound to sites that were previously unoccupied. IGF-I affinity chromatography was used to separate unoccupied 150-kDa complexes that bound to the column and were eluted with acid from complexes that contained endogenous IGF-I, did not bind to the column, and appeared in the flow-through. In competitive binding assays, IGF-binding proteins (IGFBPs) in the acid eluate bound IGF-II with higher affinity than IGF-I, whereas IGFBPs in the flow-through, after acid stripping, bound IGF-I and IGF-II with similar affinity. The acid eluate and the acid-stripped flow-through predominantly formed 50-kDa complexes with [I-125]IGF-II when affinity-cross-linked and examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis; these complexes were precipitated by antibodies to rat IGFBP-3. Larger complexes (>95 kDa) present in the nonacidified 150-kDa pool were not observed, consistent with the IGFBP-3 molecules in the flow-through and eluate having been complexed to an acid-labile subunit (ALS). By contrast, when these preparations were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis without affinity cross-linking, the flow-through contained intact IGFBP-3 (40-43 kDa), whereas the eluate contained only truncated 30-kDa IGFBP-3. We conclude that the 150-kBa fraction of adult rat serum includes 1) ternary complexes of intact IGFBP-3 (which binds IGF-I and IGF-II with similar affinity), endogenous IGF-I, and the ALS; and 2) binary complexes of proteolytically nicked IGFBP-3 and ALS that bind IGF-II preferentially. The nicked IGF-II-preferring complex is present in native serum before acidification or exposure to denaturants. RP LEE, CY (reprint author), NIDDKD, MOLEC & CELLULAR ENDOCRINOL BRANCH, GROWTH & DEV SECT,BLDG 10,ROOM 8D14,10 CTR DR, MSC 1758, BETHESDA, MD 20892 USA. NR 42 TC 30 Z9 31 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 1995 VL 136 IS 2 BP 668 EP 678 DI 10.1210/en.136.2.668 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QD586 UT WOS:A1995QD58600039 PM 7530649 ER PT J AU SUK, WA AF SUK, WA TI THE NIEHS SUPERFUND BASIC RESEARCH-PROGRAM - OVERVIEW AND AREAS OF FUTURE-RESEARCH DIRECTIONS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Joint US/Mexico Conference on Fate, Transport and Interactions of Metals CY APR 14-16, 1993 CL TUCSON, AZ DE NIEHS; HAZARDOUS SUBSTANCES; INTERDISCIPLINARY; BASIC RESEARCH; BIOLOGIC MARKERS; METALS; MIXTURES OF CHEMICALS; TECHNOLOGY TRANSFER AB The National Institute of Environmental Health Sciences' Superfund Basic Research Program is currently funding 142 separate research projects within 18 programs encompassing 29 universities and institutions around the United States. The research under this program covers a wide range of interdisciplinary science from both the biomedical and nonbiomedical perspectives. This is a unique program of technology-driven research. Nonetheless, there are some areas of research that should be investigated or investigated further, should funds become available. Environmental health risk posed by the location of Superfund sites may be distributed inequitably across socioeconomic status and racial groups. Since one in five children now lives below the poverty line, an important aspect of environmental equity must be the investigation of the health effects of environmental factors on children. The multidisciplinary investigation of the effects of hazardous substance exposure on children is an area that needs much research due to the fact that most of the toxicologic data available are based on adults and animals. This program is funding 27 projects on ecologic damage posed by hazardous wastes. Much more research is needed in the investigation of toxic effects on natural succession of ecosystems as well as on their effects on biodiversity to further our understanding of the food web in the role of bioavailability in human health, and to examine the bioaccumulation of these chemicals as it relates to their fate and transport. This program is researching and developing many innovative technologies for detecting, assessing, and reducing toxic materials in the environment. As these products are developed through basic research, it becomes necessary to design a technology-transfer strategy for this program to handle the unique problems associated with transferring multidisciplinary technology from basic research to applied research and eventually to technology demonstrations and commercialization. Two areas of prime consideration are biologically based risk assessment and bioremediation. Presently, more than half of hazardous waste remediation is done via incineration. Additional funding will allow for investigating innovative technologies in incineration, to augment studies on the health effects of exposure to toxic combustion by-products, and to develop real-time monitors for hazardous waste incinerator emissions. From a public health perspective, this technology may allow for the destruction of environmental hazardous wastes such that potential human health effects are ameliorated, or indeed prevented, specifically by reducing the amount and toxicity of hazardous substances. RP SUK, WA (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 2 Z9 2 U1 1 U2 4 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD FEB PY 1995 VL 103 SU 1 BP 3 EP 5 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA QP391 UT WOS:A1995QP39100001 PM 7621795 ER PT J AU VINEIS, P CAPORASO, N AF VINEIS, P CAPORASO, N TI TOBACCO AND CANCER - EPIDEMIOLOGY AND THE LABORATORY SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE ADDUCTS; BIOMARKERS; CANCER; GENETIC SUSCEPTIBILITY; METABOLIC POLYMORPHISMS; ONCOGENES; TOBACCO; TUMOR-SUPPRESSOR GENES; TWINS ID GLUTATHIONE-S-TRANSFERASE; CARCINOGEN-DNA ADDUCTS; LUNG-CANCER; CIGARETTE-SMOKING; BLADDER-CANCER; P53 MUTATIONS; CHEMICAL CARCINOGENESIS; HEMOGLOBIN ADDUCTS; AROMATIC-AMINES; N-NITROSAMINES AB Tobacco smoke contains many mutagenic and carcinogenic chemicals. Both whole tobacco smoke and extracts induce tumors in experimental animals. Work with carcinogen-macromolecule adducts provided evidence for the action of specific chemicals. Molecular epidemiology studies suggested that point mutations in tumor-suppressor genes (e.g., p53) and oncogenes (e.g., ras) may be specific both for the type of tumor and for the critical environmental exposure. The consistency among investigations on oncogene/tumor-suppressor gene mutations in lung cancer (and other tobacco-related cancers) in smokers is highly suggestive, although we still lack information about the time sequence between exposure, gene mutation, and cancer onset. Current work that deserves emphasis includes investigations revealing that lungs of smokers contain benzo[a]pyrene diol-epoxide-guanine DNA adducts, which are in accordance with the type of mutations found in K-ras or p53 genes (G to T transversions). In addition, DNA in human exfoliated bladder cells showed a derivative of 4-aminobiphenyl as a main adduct; there was also an association between smoking habits (amount and type of tobacco) and the levels of both DNA adducts and hemoglobin adducts formed by aromatic amines. Increasing evidence indicates that genetically based metabolic polymorphisms exert a role in modulating individual susceptibility to the action of tobacco carcinogens. Overall, the weight of evidence strongly supports the causal nature of the association between smoking and cancer and falsifies Fisher's hypothesis that the association was due to confounding by genetic predisposition. C1 NCI, GENET EPIDEMIOL BRANCH, ROCKVILLE, MD 20850 USA. RP VINEIS, P (reprint author), UNIV TURIN, DIPARTIMENTO SCI BIOMED & ONCOL UMANA, CANC EPIDEMIOL UNIT, VIA SANTENA 7, I-10126 TURIN, ITALY. NR 60 TC 69 Z9 69 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD FEB PY 1995 VL 103 IS 2 BP 156 EP 160 DI 10.2307/3432271 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA RF453 UT WOS:A1995RF45300013 PM 7737063 ER PT J AU ZIEGLER, SF MORELLA, KK ANDERSON, D KUMAKI, N LEONARD, WJ COSMAN, D BAUMANN, H AF ZIEGLER, SF MORELLA, KK ANDERSON, D KUMAKI, N LEONARD, WJ COSMAN, D BAUMANN, H TI RECONSTITUTION OF A FUNCTIONAL INTERLEUKIN (IL)-7 RECEPTOR DEMONSTRATES THAT THE IL-2 RECEPTOR-GAMMA CHAIN IS REQUIRED FOR IL-7 SIGNAL-TRANSDUCTION SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE INTERLEUKIN-7 RECEPTOR; INTERLEUKIN-2 RECEPTOR GAMMA CHAIN; SIGNAL TRANSDUCTION ID COLONY-STIMULATING FACTOR; DISTINCT CYTOPLASMIC REGIONS; HUMAN PERIPHERAL-BLOOD; PLASMA-PROTEIN GENES; COMMON BETA-SUBUNIT; TYROSINE PHOSPHORYLATION; CYTOKINE RECEPTORS; GM-CSF; PROLIFERATION; DOMAINS AB The interleukin (LL)-2 receptor gamma chain has recently been shown to be a component of the IL-7 and IL-4 receptors. Using a transient transfection assay and the trans-activation of reporter gene constructs which are under the control of cytokine-responsive promoter elements, we have studied signal transduction through the IL-7 receptor (1L-7R). The reporter gene expression was not stimulated by receptors that contained the cytoplasmic domain of the 1L-7R, either as intact IL-7R or as part of a chimeric receptor. However, co-expression of the IL-7R with the IL-2 receptor gamma chain was able to stimulate gene activation. For maximal stimulation the intact cytoplasmic domains of each chain was required. C1 TOHOKU UNIV,SCH MED,DEPT OPHTHALMOL,SENDAI,MIYAGI 980,JAPAN. IMMUNEX RES & DEV CORP,DEPT MOLEC BIOL,SEATTLE,WA. ROSWELL PK CANC INST,DEPT MOLEC & CELLULAR BIOL,BUFFALO,NY 14263. NHLBI,PULM & MOLEC IMMUNOL SECT,BETHESDA,MD 20892. NR 42 TC 40 Z9 40 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD FEB PY 1995 VL 25 IS 2 BP 399 EP 404 DI 10.1002/eji.1830250214 PG 6 WC Immunology SC Immunology GA QY506 UT WOS:A1995QY50600013 PM 7875201 ER PT J AU CHEN, ZJ WHEELER, J NOTKINS, AL AF CHEN, ZJ WHEELER, J NOTKINS, AL TI ANTIGEN-BINDING B-CELLS AND POLYREACTIVE ANTIBODIES SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE POLYREACTIVE ANTIBODY; B CELLS; ANTIGEN BINDING ID EPSTEIN-BARR VIRUS; SYSTEMIC LUPUS-ERYTHEMATOSUS; MONOREACTIVE HIGH-AFFINITY; CD5+ LYMPHOCYTE-B; MONOCLONAL AUTOANTIBODIES; RHEUMATOID-FACTOR; MULTIPLE ORGANS; IMMUNOGLOBULIN RECEPTORS; CLONAL ANALYSIS; RABIES VIRUS AB The present experiments were initiated to see if cells capable of binding antigens could make polyreactive antibodies. Fluorescein isothiocyanate-labeled self and non-self antigens were incubated with B cells from normal individuals. Antigen-binding cells were separated from non-antigen-binding cells by flow cytometry, immortalized with Epstein-Ban virus and analyzed at the clonal level for their capacity to make polyreactive antibodies. Four to six times more cells making polyreactive antibodies were found in the B cell subset that bound antigens than in the B cell subset that did not bind antigens. The majority of the polyreactive antibodies were of the immunoglobulin (Ig)M isotype. Immunoflow cytometry revealed that cell lines making polyreactive antibodies bound a variety of antigens (e.g., insulin, IgGFc and beta-galactosidase), whereas cell lines making monoreactive antibodies bound only a single antigen. The binding of antigens to B cell lines that made polyreactive antibodies could be inhibited (range, 28 %-57 %) by both homogeneous and heterogeneous antigens. Both CD5(+) and CD5(-) antigen-binding B cells made polyreactive antibodies, but the frequency was slightly higher in the CD5(+) antigen-binding (85 %) as compared to the CD5(-) antigen-binding (50 %) population. Comparison of CD5(+) B cells that bound antigens with CD5(+) B cells that did not bind antigens showed that approximately 86 % of the former, but only 15 % of the latter, made polyreactive antibodies. It is concluded that cells capable of binding a variety of different antigens can make polyreactive antibodies and that antigen binding is a good marker for identifying polyreactive antibody-producing cells. RP CHEN, ZJ (reprint author), NIDR,ORAL MED LAB,BLDG 30,ROOM 121,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 39 TC 32 Z9 35 U1 0 U2 2 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD FEB PY 1995 VL 25 IS 2 BP 579 EP 586 DI 10.1002/eji.1830250241 PG 8 WC Immunology SC Immunology GA QY506 UT WOS:A1995QY50600040 PM 7533091 ER PT J AU LOWY, RJ SARKAR, DP WHITNALL, MH BLUMENTHAL, R AF LOWY, RJ SARKAR, DP WHITNALL, MH BLUMENTHAL, R TI DIFFERENCES IN DISPERSION OF INFLUENZA-VIRUS LIPIDS AND PROTEINS DURING FUSION SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID HEMAGGLUTININ SURFACE-DENSITY; INDUCED MEMBRANE-FUSION; CELL-CELL FUSION; LATERAL MOBILITY; SENDAI VIRUS; FLUORESCENCE; PH; ERYTHROCYTES; EVENTS; GLYCOPROTEINS AB Digitally enhanced low-light-level fluorescence video microscopy and immunochemical staining were used to examine influenza virus envelope lipid and protein redistribution during pH-induced fusion. Video microscopy was performed using viruses labeled with either the lipid analogue octadecylrhodamine B (R18) or fluorescein isothiocyanate (FITC) covalently linked to envelope proteins. Viruses were bound to human red blood cells, and the pattern and intensity of fluorescence were monitored for 30 min while cell-virus complexes were perfused with pH 7.4 or 4.8 media at temperatures either above or below 20 degrees C. R18 showed complete redistribution and dequenching by 30 min at all incubation temperatures, confirming reports that viral fusion occurs at subphysiological temperatures. FITC-labeled protein showed spatial redistribution at 28 degrees C but no change at low temperature. Electron microscopy observations of immunochemical staining of viral proteins confirmed both that protein redistribution at 37 degrees C was slower than R18 and the failure of movement within 30 min at 16 degrees C. Video microscopy monitoring of RNA staining by acridine orange of virus-cell complexes showed redistribution to the RBCs at all temperatures but only after low pH-induced fusion. The results are consistent with differential dispersion of viral components into the RBC and the existence of relatively long-lived barriers to diffusion subsequent to fusion pore formation. C1 UNIV DELHI, DEPT BIOCHEM, NEW DELHI, INDIA. NCI, LMMB, MEMBRANE STRUCT & FUNCT SECT, BETHESDA, MD USA. RP ARMED FORCES RADIOBIOL RES INST, DEPT PHYSIOL, BETHESDA, MD 20889 USA. NR 45 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 EI 1090-2422 J9 EXP CELL RES JI Exp. Cell Res. PD FEB PY 1995 VL 216 IS 2 BP 411 EP 421 DI 10.1006/excr.1995.1052 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA QG014 UT WOS:A1995QG01400017 PM 7843286 ER PT J AU BETTELHEIM, FA QIN, CA ZIGLER, JS AF BETTELHEIM, FA QIN, CA ZIGLER, JS TI CALCIUM CATARACT - A MODEL FOR OPTICAL ANISOTROPY FLUCTUATIONS SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE BIREFRINGENCE; CALCIUM CATARACT; LENS; OPTICAL ANISOTROPY; VIMENTIN ID RAT LENS; PROTEINS; BIREFRINGENCE; CLEAVAGE; CALPAIN; EYE AB Young rat lenses were incubated in organ culture media enriched with 20 mM calcium. Lenses in the calcium rich medium developed cataracts and were characterized by the absence of vimentin in the urea soluble protein fractions. Sections from the same lenses were studied by polarized light scattering. The I-+/I-parallel to scattering intensity ratios were higher from the lenses in calcium-rich media than from the control lenses. This indicated an increase in the optical anisotropy fluctuations during cataractogenesis. The turbidity that developed due to these fluctuations was caused partly by the disappearance of vimentin and which in turn caused the enhancement of birefringence of the lens. C1 NEI,BETHESDA,MD 20892. RP BETTELHEIM, FA (reprint author), ADELPHI UNIV,DEPT CHEM,GARDEN CITY,NY 11530, USA. FU NEI NIH HHS [EY-02571] NR 26 TC 12 Z9 12 U1 0 U2 2 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD FEB PY 1995 VL 60 IS 2 BP 153 EP 157 DI 10.1016/S0014-4835(95)80005-0 PG 5 WC Ophthalmology SC Ophthalmology GA QG365 UT WOS:A1995QG36500005 PM 7781743 ER PT J AU POLTORAK, M KHOJA, I HEMPERLY, JJ WILLIAMS, JR ELMALLAKH, R FREED, WJ AF POLTORAK, M KHOJA, I HEMPERLY, JJ WILLIAMS, JR ELMALLAKH, R FREED, WJ TI DISTURBANCES IN CELL RECOGNITION MOLECULES (N-CAM AND L1 ANTIGEN) IN THE CSF OF PATIENTS WITH SCHIZOPHRENIA SO EXPERIMENTAL NEUROLOGY LA English DT Article ID MYELIN-ASSOCIATED GLYCOPROTEIN; IMMUNOELECTRON MICROSCOPIC LOCALIZATION; INTERCELLULAR-ADHESION MOLECULE-1; HIPPOCAMPAL PYRAMIDAL CELL; CEREBROSPINAL-FLUID; L1/NG-CAM EXPRESSION; EXTRACELLULAR-MATRIX; SCIATIC-NERVE; PROTEIN; SERUM AB Although the pathogenesis of schizophrenia is unknown, there are data which indicate that the disease may be due to neurodevelopmental disturbances. Cell recognition molecules such as N-CAM and L1 antigen are involved in cell-cell interactions during development and in plasticity of the nervous system and could therefore be altered in relation to ongoing or established pathological processes. Using the Western blot technique, we found significant increases in N-CAM immunoreactive proteins and decreases in L1 antigen in the CSF of schizophrenic patients as compared to normal controls. The decrease in L1 antigen was observed in the 140-kDa band, and N-CAM was increased only in the 120-kDa band. The 120-kDa band of N-CAM and the 140-kDa band of L1 antigen were prominent components of CSF, but in serum these bands were minor or not detectable. Neuroleptic treatment did not significantly change either N-CAM or L1 antigen concentrations in CSF. It is possible that these CSF proteins are derived from CNS cells as secreted soluble N-CAM isoforms and L1 peptides. Our results suggest the possibility of a specific pattern of abnormal cellular function in the CNS in schizophrenia. (C) 1995 Academic Press, Inc. C1 BECTON DICKINSON RES CTR,RES TRIANGLE PK,NC 27709. RP POLTORAK, M (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032, USA. NR 57 TC 71 Z9 73 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD FEB PY 1995 VL 131 IS 2 BP 266 EP 272 DI 10.1016/0014-4886(95)90048-9 PG 7 WC Neurosciences SC Neurosciences & Neurology GA QP939 UT WOS:A1995QP93900011 PM 7895825 ER PT J AU BRINDLEY, PJ GAM, AA MCKERROW, JH NEVA, FA AF BRINDLEY, PJ GAM, AA MCKERROW, JH NEVA, FA TI SS40 - THE ZINC ENDOPEPTIDASE SECRETED BY INFECTIVE LARVAE OF STRONGLOIDES STERCORALIS SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE PARASITIC NEMATODE; STRONGYLOIDES STERCORALIS; SECRETED PROTEINASE; ZINC ENDOPEPTIDASE; IMMUNITY; ALLERGEN; PNGASE F, PEPTIDE ID STRONGYLOIDES-STERCORALIS; TISSUE INVASION; PROTEINASE; PROTEASE AB Infective larvae of a pathogenic nematode of humans, Strongyloides stercoralis, release a potent zinc endopeptidase activity which has a broad substrate specificity for constituents of extracellular dermal matrix, including elastin. Specific inhibitors of zinc endopeptidases prevent the penetration of mammalian skin by S. stercoralis larvae. We now report the molecular size and isoelectric point of the S. stercoralis zinc endopeptidase at 40 kDa, pI 5 by zymogram analysis. The activity was not influenced by incubation with P-mercaptoethanol at 22 degrees C, but was inactivated by incubation at 100 degrees C for 2 min. The enzyme, which we term Ss40, is immunogenic and stimulates humoral IgG antibodies during infection of humans; the activity was immunoprecipitable from ES with pooled infection sera. In addition, a HPLC-enricbed Ss40 preparation stimulated the release of histamine from peripheral blood leukocytes of S. stercoralis-infected persons, suggesting that Ss40 is allergenic in humans. (C) 1995 Academic Press, Inc. C1 UNIV CALIF SAN FRANCISCO,SCH MED,DEPT PATHOL,SAN FRANCISCO,CA 94143. QUEENSLAND INST MED RES,BRISBANE,QLD 4029,AUSTRALIA. RP BRINDLEY, PJ (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. NR 19 TC 29 Z9 29 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD FEB PY 1995 VL 80 IS 1 BP 1 EP 7 DI 10.1006/expr.1995.1001 PG 7 WC Parasitology SC Parasitology GA QD589 UT WOS:A1995QD58900001 PM 7529715 ER PT J AU YUAN, JH GOEHL, TJ ABDO, K CLARK, J ESPINOSA, O BUGGE, C GARCIA, D AF YUAN, JH GOEHL, TJ ABDO, K CLARK, J ESPINOSA, O BUGGE, C GARCIA, D TI EFFECTS OF GAVAGE VERSUS DOSED FEED ADMINISTRATION ON THE TOXICOKINETICS OF BENZYL ACETATE IN RATS AND MICE SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article ID PERCUTANEOUS-ABSORPTION; BENZYL ACETATE; SKIN INVITRO; GLYCINE; METABOLISM; AVAILABILITY; DISPOSITION; VEHICLE; INVIVO; ACID AB Effects of gavage versus dosed feed administration on the toxicokinetics of benzyl acetate were studied in male F344 rats and B6C3F(1) mice. Benzyl acetate was rapidly hydrolysed to benzyl alcohol and then oxidized to benzoic acid. After gavage administration of benzyl acetate in corn oil at 500 mg/kg (rats) and 1000 mg/kg (mice), high benzoic acid plasma concentrations were observed. In contrast, much lower benzoic acid plasma concentrations were found after dosed feed administration at about 615 mg/kg/day for rats and about 850 mg/kg/day for mice. Results show that although the daily doses of benzyl acetate are comparable, bolus gavage administration effectively saturated the benzoic add elimination pathway whereas dosed feed administration did not. In contrast, hippuric acid plasma concentrations were similar after both gavage and dosed feed administration due to the depletion of the glycine supply pool. Study results could explain the different toxicity and carcinogenicity responses of benzyl acetate observed in 2-yr chronic gavage and dosed feed studies. C1 NIEHS,RES TRIANGLE PK,NC 27709. CEDRA CORP,AUSTIN,TX 78754. NR 26 TC 16 Z9 17 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD FEB PY 1995 VL 33 IS 2 BP 151 EP 158 DI 10.1016/0278-6915(94)00123-6 PG 8 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA QQ759 UT WOS:A1995QQ75900007 PM 7868001 ER PT J AU BOCKMAN, DE SHARP, R MERLINO, G AF BOCKMAN, DE SHARP, R MERLINO, G TI REGULATION OF TERMINAL DIFFERENTIATION OF ZYMOGENIC CELLS BY TRANSFORMING GROWTH-FACTOR-ALPHA IN TRANSGENIC MICE SO GASTROENTEROLOGY LA English DT Article ID HUMAN PANCREATIC-CANCER; FACTOR RECEPTOR FAMILY; GASTROINTESTINAL-TRACT; MENETRIERS DISEASE; GASTRIC-CARCINOMA; EPITHELIAL-CELLS; MOUSE STOMACH; LOCALIZATION; EXPRESSION; OVEREXPRESSION AB Background/Aims: Transforming growth factor (TGF) alpha affects the growth of gastric mucosa. Its overexpression alters the mucosa. The aim of this study was to test the possibility that it regulates differentiation of gland cells. Methods: Transgenic mice that overexpress TGF-alpha were used to detect its effect on zymogenic (chief) cells in the stomach. To test for a general regulatory role of TGF-alpha in differentiation of zymogen-producing cells, salivary glands from transgenic mice were studied. Results: In these mice, messenger RNA for pepsinogen C is present in the stomach at normal levels during the neonatal period and then decreases markedly. Zymogenic cells are present in the stomach during the neonatal period but are missing in transgenic adults. The bases of gastric glands, normally rich in zymogenic cells, are occupied by undifferentiated cells and mucous neck cells, the precursors of zymogenic cells. Zymogen granules in submandibular glands of transgenic female mice are reduced in number. Zymogen granule-containing cells in the parotid gland undergo redifferentiation to form tubular complexes, collections of ductularlike structures like those formed in the transgenic pancreas. Conclusions: TGF a is a major participant in the regulation of terminal differentiation of zymogenic cells in the stomach and salivary glands. C1 NCI,MOLEC BIOL LAB,BETHESDA,MD. RP BOCKMAN, DE (reprint author), MED COLL GEORGIA,DEPT CELLULAR BIOL & ANAT,AUGUSTA,GA 30912, USA. NR 34 TC 37 Z9 38 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 1995 VL 108 IS 2 BP 447 EP 454 DI 10.1016/0016-5085(95)90073-X PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QE148 UT WOS:A1995QE14800019 PM 7835587 ER PT J AU SHULDINER, AR NIRULA, A SCOTT, LA AF SHULDINER, AR NIRULA, A SCOTT, LA TI DETERMINATION OF THE GENOMIC STRUCTURES OF 2 NONALLELIC PREPROINSULIN GENES IN XENOPUS-LAEVIS USING THE POLYMERASE CHAIN-REACTION SO GENERAL AND COMPARATIVE ENDOCRINOLOGY LA English DT Article ID INSULIN GENE; ENDOCRINE-CELLS; GROWTH-FACTOR; CDNA CLONING; II GENE; RAT; EXPRESSION; SEQUENCE; NEURONS; EVOLUTION AB We have previously cloned cDNAs that correspond to two different nonallelic preproinsulin genes in the amphibian, Xenopus laevis (Shuldiner et al., 1989, J. Biol. Chem. 264, 9428-9432). The coding regions of the two genes are very similar (i.e., 93% amino acid identity). While both preproinsulin genes are expressed coordinately in the adult pancreas, they are differentially expressed in prepancreatic embryos during neurulation (Shuldiner et al., 1991, Proc. Natl. Acad. Sci. USA 88, 7679-7683). We now report the use of the polymerase chain reaction (PCR) to investigate the genomic structures of both Xenopus preproinsulin genes. First, the nucleotide sequence of a portion of the 5' untranslated region that was lacking in our cDNA clones was obtained using rapid amplification of cDNA ends (5' RACE). Then, oligonucleotide primers were designed that flanked putative exon-intron splice boundaries, and intronic sequences in each of the two nonallelic genes were amplified. We determined that both Xenopus preproinsulin genes contain two introns, one interrupting the 5' untranslated region, and the second interrupting the region encoding the C-peptide. The introns are similar in position, but of greater length than those reported in most other species. Interestingly, dideoxy sequence analysis of the PCR-amplified introns revealed that the exon-intron splice junctions are well conserved between the two nonallelic genes, but internal to these junctions, the respective introns diverge significantly from each other. Thus, ample time has elapsed since the duplication of these two genes for marked divergence to occur within the introns suggesting that these regions are not important for expression in the adult pancreas. From these studies, we predict that elucidation of the sequences of the 5' flanking regions of the two nonallelic preproinsulin genes will reveal conserved regions that will be important for coordinate expression, as well as less conserved regions that will either be unimportant for coordinate expression (i.e., pancreatic expression) or important for differential expression (i.e., prepancreatic expression). (C) 1995 Academic Press, Inc. C1 NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. RP SHULDINER, AR (reprint author), JOHNS HOPKINS UNIV,SCH MED,DIV GERIAT MED & GERONTOL,BALTIMORE,MD, USA. NR 38 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0016-6480 J9 GEN COMP ENDOCR JI Gen. Comp. Endocrinol. PD FEB PY 1995 VL 97 IS 2 BP 220 EP 230 DI 10.1006/gcen.1995.1021 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QH618 UT WOS:A1995QH61800006 PM 7542614 ER PT J AU FOLEY, DJ MILES, TP BROCK, DB PHILLIPS, C AF FOLEY, DJ MILES, TP BROCK, DB PHILLIPS, C TI RECOUNTS OF ELDERLY DEATHS - ENDORSEMENTS FOR THE PATIENT SELF-DETERMINATION ACT SO GERONTOLOGIST LA English DT Note DE AGING; MORTALITY; ADVANCE DIRECTIVES ID ADVANCE DIRECTIVES; CARE AB Circumstances in the last 3 days of life were examined for a sample of 1,227 elderly decedents in Fairfield County, Connecticut, in 1985. Interviews were with a surviving next-of-kin or a nonrelative about 3 months after the event of death. Most decedents were in a hospital or a nursing home the night before death (45% and 24%, respectively). In the days preceding death, about 34% of the decedents knew that death was impending and about 40% had difficulty recognizing family members. These and other findings support the need for elderly people to complete advance directives. C1 NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. RP FOLEY, DJ (reprint author), NIA,GATEWAY BLDG,SUITE 309,7201 WISCONSIN AVE,BETHESDA,MD 20892, USA. OI Miles, Toni/0000-0003-0823-2319 FU NIA NIH HHS [N01-AG-2-2137] NR 12 TC 10 Z9 10 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD FEB PY 1995 VL 35 IS 1 BP 119 EP 121 PG 3 WC Gerontology SC Geriatrics & Gerontology GA QG438 UT WOS:A1995QG43800015 PM 7890197 ER PT J AU THOTAKURA, NR BLITHE, DL AF THOTAKURA, NR BLITHE, DL TI GLYCOPROTEIN HORMONES - GLYCOBIOLOGY OF GONADOTROPINS, THYROTROPIN AND FREE ALPHA-SUBUNIT SO GLYCOBIOLOGY LA English DT Review DE DEGLYCOSYLATION; GLYCOPROTEIN HORMONES; GONADOTROPIN FREE ALPHA SUBUNIT; GONADOTROPINS; OLIGOSACCHARIDES ID HUMAN CHORIONIC-GONADOTROPIN; ASPARAGINE-LINKED OLIGOSACCHARIDES; INDIVIDUAL GLYCOSYLATION SITES; FOLLICLE-STIMULATING-HORMONE; HAMSTER OVARY CELLS; METABOLIC-CLEARANCE; SIGNAL-TRANSDUCTION; BIOLOGICAL-ACTIVITY; BETA-SUBUNIT; SIALYLATED OLIGOSACCHARIDES AB Chorionic gonadotrophin and pituitary luteinizing hormone, follicle-stimulating hormone and thyroid-stimulating hormone comprise the family of glycoprotein hormones, which regulate major metabolic and reproductive functions of the body, These are heterodimeric glycoproteins composed of a common alpha subunit and a hormone-specific beta subunit. The N-linked oligosaccharides of these hormones are necessary for proper folding, assembly, secretion, metabolic clearance and biological activity, The free alpha subunit, which is shown to have a physiological function, is maintained in the uncombined form due to its glycan structures, The N-glycans of the glycoprotein hormones contain a variety of terminal residues, which are responsible for the differential targeting and clearance of the hormones, Glycosylation of these hormones is regulated by a variety of physiological and pathological conditions, leading to subtle alterations in their bioactivities, Recent studies on the structures and specific functions of different glycans of natural and recombinant glycoprotein hormones have provided valuable insight into the glycobiology of these hormones, This information will be useful in the development of diagnostic and therapeutic applications of the glycoprotein hormones. C1 NIDDKD,MOLEC & CELLULAR ENDOCRINOL BRANCH,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 74 TC 71 Z9 71 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD FEB PY 1995 VL 5 IS 1 BP 3 EP 10 DI 10.1093/glycob/5.1.3 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QL006 UT WOS:A1995QL00600001 PM 7539645 ER PT J AU GUEXCROSIER, Y PITTET, N HERBORT, CP AF GUEXCROSIER, Y PITTET, N HERBORT, CP TI THE EFFECT OF THALIDOMIDE AND SUPIDIMIDE ON ENDOTOXIN-INDUCED UVEITIS IN RATS SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; VERSUS-HOST DISEASE; BEHCETS SYNDROME AB Background: Endotoxin-induced uveitis (EIU) is an animal model of ocular inflammation, produced by footpad injection of endotoxin (lipopolysaccharide, LPS) to mimic the human disease of acute anterior uveitis, that is useful for testing new anti-inflammatory therapy. The purpose of this study was to test the anti-inflammatory effect on EIU of thalidomide and one of its derivatives, supidimide. Methods: EIU was produced in rats by hind footpad injection of LPS (100 mug/animal). Animals were killed 20 h after LPS injection. Inflammation was evaluated by anterior chamber determination of proteins and cells. Results: A dosage of 400 mg/kg per day of thalidomide was efficient in reducing inflammation whether given in three doses (at -24 h, -4 h and +4 h relative to LPS challenge = THAL-1; p < 0.001 for proteins and cells), in two doses (-4 h and +4 h = THAL-2; p < 0.001 for proteins, p less-than-or-equal-to 0.012 for cells) or in one dose (at +4 h = late THAL; p < 0.001 for proteins, p less-than-or-equal-to 0.02 for cells). A dosage of 300 mg/kg per day, of thalidomide was still efficient (p less-than-or-equal-to 0.023 for proteins, p less-than-or-equal-to 0.06 for cells), but 150 mg/kg per day had no effect on inflammation. Supidimide (400 mg/kg per day) had some anti-inflammatory effect (p less-than-or-equal-to 0.053 for proteins, p less-than-or-equal-to 0.06 for cells). Conclusion: High-dose thalidomide had a potent anti-inflammatory effect in EIU, but lower doses were not sufficient to reduce inflammation. At similar high doses, supidimide had some effect on EIU but was less effective than thalidomide. C1 UNIV LAUSANNE,HOP JULES GONIN,DEPT OPHTHALMOL,CH-1004 LAUSANNE,SWITZERLAND. NEI,BETHESDA,MD 20892. NR 14 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD FEB PY 1995 VL 233 IS 2 BP 90 EP 93 DI 10.1007/BF00241478 PG 4 WC Ophthalmology SC Ophthalmology GA QE410 UT WOS:A1995QE41000008 PM 7729710 ER PT J AU MCKINNON, RA BURGESS, WM HALL, PDLM ROBERTSTHOMSON, SJ GONZALEZ, FJ MCMANUS, ME AF MCKINNON, RA BURGESS, WM HALL, PDLM ROBERTSTHOMSON, SJ GONZALEZ, FJ MCMANUS, ME TI CHARACTERIZATION OF CYP3A GENE SUBFAMILY EXPRESSION IN HUMAN GASTROINTESTINAL TISSUES SO GUT LA English DT Article DE CYTOCHROMES P450; MUTAGEN ACTIVATION; IN SITU HYBRIDIZATION ID HUMAN-LIVER; MESSENGER-RNA; HUMAN CYTOCHROME-P-450; NIFEDIPINE OXIDASE; FETAL LIVER; EXTRAHEPATIC TISSUES; INSITU HYBRIDIZATION; MONOCLONAL-ANTIBODY; INTESTINAL-MUCOSA; CDNA AB The human CYP3A subfamily is of interest due to its multiplicity, activity toward known carcinogens, and extrahepatic expression. In situ hybridisation analysis of formalin fixed, routinely processed biopsy specimens was used to localise CYP3A mRNA in human gastrointestinal tissues from several individuals. CYP3A mRNA is abundant in human liver and in mucosal epithelial cells of all segments of the human small intestine. RNA blot analyses showed that the mRNA species observed in most livers and in human small intestine represent CYP3A3/3A4 transcripts. This was confirmed at the protein level by immunoblot comparison of small intestine microsomes to in vitro expressed CYP3A4 and CYP3A5 proteins. In liver and small intestine, CYP3A mRNA is not uniformly distributed, with grain density highest in cells within the respective non-proliferative compartments. CYP3A mRNA was also observed in human oesophagus and colon. RNA blot analysis of multiple colons showed heterogeneity in the CYP3A mRNAs present. Two CYP3A mRNAs (CYP3A3/3A4 and CYP3A5) were detected in colon samples from several individuals. In addition to those localisation studies, the capacity of expressed CYP3A4 and CYP3A5 to activate the dietary heterocyclic amine MeIQ in the presence of alpha-naphthoflavone was shown. These results show that there is considerable heterogeneity in the expression of the CYP3A subfamily in human gastrointestinal tissues. C1 UNIV QUEENSLAND,DEPT PHYSIOL & PHARMACOL,BRISBANE,QLD 4072,AUSTRALIA. FLINDERS UNIV S AUSTRALIA,DEPT CLIN PHARMACOL,BEDFORD PK,SA 5042,AUSTRALIA. FLINDERS UNIV S AUSTRALIA,DEPT HISTOPATHOL,BEDFORD PK,SA 5042,AUSTRALIA. UNIV SYDNEY,DEPT PHARM,SYDNEY,NSW 2025,AUSTRALIA. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RI McKinnon, Ross /B-9340-2009; Roberts-Thomson, Sarah/B-4282-2011 OI McKinnon, Ross /0000-0002-3725-793X; Roberts-Thomson, Sarah/0000-0001-8202-5786 NR 48 TC 111 Z9 114 U1 0 U2 3 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0017-5749 J9 GUT JI Gut PD FEB PY 1995 VL 36 IS 2 BP 259 EP 267 DI 10.1136/gut.36.2.259 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QE203 UT WOS:A1995QE20300020 PM 7883227 ER PT J AU HILL, HA COATES, RJ AUSTIN, H CORREA, P ROBBOY, SJ CHEN, V CLICK, LA BARRETT, RJ BOYCE, JG KOTZ, HL HARLAN, LC AF HILL, HA COATES, RJ AUSTIN, H CORREA, P ROBBOY, SJ CHEN, V CLICK, LA BARRETT, RJ BOYCE, JG KOTZ, HL HARLAN, LC TI RACIAL-DIFFERENCES IN TUMOR GRADE AMONG WOMEN WITH ENDOMETRIAL CANCER SO GYNECOLOGIC ONCOLOGY LA English DT Article ID BREAST-CANCER; REPLACEMENT THERAPY; MYOMETRIAL INVASION; ORAL-CONTRACEPTIVES; ESTROGEN THERAPY; RISK; SURVIVAL; CARCINOMA; DIET; ASSOCIATIONS AB Black women with endometrial cancer have more advanced disease and less favorable tumor grade than do white women. This study evaluated whether racial differences in tumor grade could be explained by hormone-related factors and other putative determinants of grade. Subjects included 207 white and 81 black postmenopausal women diagnosed with primary cancer of the uterine corpus between 1985 and 1987. Blacks had poorer tumor grade than whites (odds ratio for FIGO grade 2 versus grade 1 is 1.8; odds ratio for grade 3 versus grade 1 is 2.8). Over 75% of the excess of poorly differentiated tumors versus well-differentiated tumors among blacks could be explained by racial differences in use of replacement estrogens, age at first pregnancy, history of oophorectomy, poverty, stage of disease, use of screening, and access to health care. The most prominent factor was estrogen therapy, which was associated with favorable tumor grade and was used much less frequently by blacks. Although not statistically significant, a moderate racial difference in tumor grade remained after control of the potential explanatory variables. This may reflect true biologic variation between blacks and whites and may explain, in part, the observation that blacks with endometrial cancer have a worse prognosis. (C) 1995 Academic Press, Inc. C1 LOUISIANA STATE UNIV,MED CTR,DEPT PATHOL,NEW ORLEANS,LA 70112. DUKE UNIV,MED CTR,DEPT PATHOL OBSTET & GYNECOL,DURHAM,NC 27706. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC 27109. SUNY HLTH SCI CTR,DEPT OBSTET & GYNECOL,BROOKLYN,NY 11203. GEORGE WASHINGTON UNIV HOSP,DEPT OBSTET & GYNECOL,WASHINGTON,DC. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. RP HILL, HA (reprint author), EMORY UNIV,ROLLINS SCH PUBL HLTH,DEPT EPIDEMIOL,ATLANTA,GA 30322, USA. NR 42 TC 37 Z9 37 U1 2 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD FEB PY 1995 VL 56 IS 2 BP 154 EP 163 DI 10.1006/gyno.1995.1024 PG 10 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA QN340 UT WOS:A1995QN34000002 PM 7896178 ER PT J AU LEE, JH KLEIN, HG AF LEE, JH KLEIN, HG TI COLLECTION AND USE OF CIRCULATING HEMATOPOIETIC PROGENITOR CELLS SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID BLOOD STEM-CELLS; COLONY-STIMULATING FACTOR; HIGH-DOSE CYCLOPHOSPHAMIDE; CHRONIC GRANULOCYTIC-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; AUTOLOGOUS BONE-MARROW; NON-HODGKINS-LYMPHOMA; PERIPHERAL-BLOOD; FLOW-CYTOMETRY AB Although lymphocytes and monocytes are becoming increasingly important in transfusion therapy, peripheral stem cells have been responsible for the recent explosive interest in harvesting mononuclear cells from the peripheral circulation. Despite their low concentration in peripheral blood and the consequent difficulty in cell collection, circulating hematopoietic progenitor cells are collected and used almost routinely. These mononuclear cells, possessing the capacity for hematopoietic reconstitution and the potential for definitive therapy of a variety of disorders, have been the focus of recent intense interest in transfusion medicine. RP LEE, JH (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BLDG 10,ROOM 1C-711,BETHESDA,MD 20892, USA. NR 111 TC 12 Z9 12 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD FEB PY 1995 VL 9 IS 1 BP 1 EP 22 PG 22 WC Oncology; Hematology SC Oncology; Hematology GA QE759 UT WOS:A1995QE75900002 PM 7737936 ER PT J AU LEE, JH KLEIN, HG AF LEE, JH KLEIN, HG TI CELLULAR GENE-THERAPY SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID HEMATOPOIETIC STEM-CELLS; HUMAN ADENOSINE-DEAMINASE; CHRONIC GRANULOMATOUS-DISEASE; LONG-TERM EXPRESSION; SEVERE COMBINED IMMUNODEFICIENCY; VECTOR-MEDIATED TRANSFER; BETA-GLOBIN GENE; BONE-MARROW; RETROVIRAL VECTORS; HUMAN GLUCOCEREBROSIDASE AB During the last decade, molecular genetic techniques have been used increasingly to transfer human genes into mammalian cells, to correct and enhance cell function, and finally to treat human disease. Despite the current obstacles to developing even the simplest therapeutic strategy, gene therapy promises to have an almost unlimited future. The ability to collect specific blood cells in large numbers, to manipulate their expansion, growth, and differentiation in vitro, and also to cryopreserve these cells for later use has been central to the early developments in gene therapy. This article reviews the major concepts involved in blood cell-based gene therapy, a model for all somatic cell gene therapy. RP LEE, JH (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BLDG 10,ROOM 1C-711,BETHESDA,MD 20892, USA. NR 98 TC 7 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD FEB PY 1995 VL 9 IS 1 BP 91 EP 113 PG 23 WC Oncology; Hematology SC Oncology; Hematology GA QE759 UT WOS:A1995QE75900005 PM 7737946 ER PT J AU DEMETRIS, AJ SEABERG, EC BATTS, KP FERRELL, LD LUDWIG, J MARKIN, RS BELLE, SH DETRE, K AF DEMETRIS, AJ SEABERG, EC BATTS, KP FERRELL, LD LUDWIG, J MARKIN, RS BELLE, SH DETRE, K TI RELIABILITY AND PREDICTIVE VALUE OF THE NATIONAL-INSTITUTE-OF-DIABETES-AND-DIGESTIVE-AND-KIDNEY-DISEASES LIVER-TRANSPLANTATION DATABASE NOMENCLATURE AND GRADING SYSTEM FOR CELLULAR REJECTION OF LIVER ALLOGRAFTS SO HEPATOLOGY LA English DT Article ID RENAL-ALLOGRAFTS; BIOPSY; STANDARDIZATION; CLASSIFICATION; PATHOLOGY; DIAGNOSIS; HEART AB Pathologists participating in the National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplant Database (LTD) created a histopathological grading system for acute liver allograft rejection, and tested it first for inter- and intra-rater reliability among a group of five pathologists experienced in liver and transplantation pathology, Specimens from post-transplantation biopsies from 48 patients with rejection, hepatitis, or other diagnosis(es) were reviewed. There was moderate to good (kappa = 0.40 to 0.55) inter-rater and good (kappa = 0.55 to 0.58) intrarater agreement for the diagnosis and exact grading of mild, moderate, or severe acute rejection, which improved when a short clinical history was provided. Thus, the scheme was reproducible, and few of the disagreements among the pathologists would have affected treatment decisions. Secondly, the ability of the grading system to predict an unfavorable short- or long-term outcome from the initial histopathological diagnosis of cellular rejection was tested on groups of 168 and 133 patients, respectively, from the three LTD clinical centers, who were followed up for at least 6 months after the first onset of rejection, This analysis showed that a higher histopathological grade of acute rejection on first biopsy diagnosis was significantly associated (P less than or equal to .006) with both an unfavorable short-term outcome, defined by failure of the episode to resolve within 21 days or the need for aggressive immunosuppressive treatment, and a long-term outcome defined by death or retransplantation from rejection within 6 months of onset. Lastly, an analysis was performed to determine whether subjective rejection grading by the pathologist or certain ''objective'' histopathological features identified by logistic regression modeling were more accurate in predicting an unfavorable outcome. The sensitivity (.86 vs. .71), specificity (.68 vs. .75), positive predictive value (.13 vs. .14), and negative predictive value (.99 vs. .98) for predicting an unfavorable long-term outcome (allograft loss from rejection within 6 months of onset) were similar for both prediction methods, although the comparison favored the logistic regression model. The low positive predictive value of both methods was attributed to the current immunosuppressive agents, which are highly effective in the prevention of liver allograft failure from acute rejection, and the difficulty in separating rejection grading from staging. To our knowledge, this study represents the first attempt to evaluate both the reproducibility and predictive value of a histopathological grading system for allograft rejection, using multiple pathologists and patients from more than one center. C1 UNIV PITTSBURGH, NIDDK, LIVER TRANSPLANTAT DATABASE, PITTSBURGH, PA 15213 USA. MAYO CLIN, DEPT PATHOL, NEW YORK, NY USA. UNIV CALIF SAN FRANCISCO, DEPT PATHOL, SAN FRANCISCO, CA USA. UNIV NEBRASKA, DEPT PATHOL, LINCOLN, NE 68583 USA. UNIV PITTSBURGH, GRAD SCH PUBL HLTH, DEPT PATHOL, PITTSBURGH, PA USA. RP DEMETRIS, AJ (reprint author), UNIV PITTSBURGH, PITTSBURGH TRANSPLANT INST, DEPT PATHOL, DIV TRANSPLANTAT, E1548 BIOMED SCI TOWER, PITTSBURGH, PA 15213 USA. NR 28 TC 56 Z9 60 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD FEB PY 1995 VL 21 IS 2 BP 408 EP 416 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RB789 UT WOS:A1995RB78900022 PM 7843714 ER PT J AU GARZINODEMO, A GALLO, RC ARYA, SK AF GARZINODEMO, A GALLO, RC ARYA, SK TI HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-2 (HIV-2) - PACKAGING SIGNAL AND ASSOCIATED NEGATIVE REGULATORY ELEMENT SO HUMAN GENE THERAPY LA English DT Article ID ACID-BINDING-PROTEINS; LONG TERMINAL REPEAT; ROUS-SARCOMA VIRUS; TRANSACTIVATOR TAT; LEUKEMIA VIRUSES; GENE-TRANSFER; GENOMIC RNA; RETROVIRUS; SEQUENCES; MUTANT AB Human immunodeficiency virus type 2 (HIV-2)-based retroviral vectors will have several desirable features as vehicles for gene therapy. These include target cell specificity, regulated expression, and attenuated cytopathicity. Such vectors require efficient packaging of RNA into retroviral particles which depends on a cis-acting sequence element called packaging signal or psi site. For most retroviruses, the principal part of this element is located between the major splice donor site and the gag initiator codon (AUG) in the leader sequence. The deletion of the corresponding region of HIV-2 did indeed cause a packaging defect; however, it did not abolish RNA encapsidation and viral infectivity. Additionally, deletions in this region resulted in an increase in intracellular viral RNA and extracellular p27 core antigen. However, only a fraction of the intracellular viral RNA was packaged into mature particles. These effects appeared to be sequence specific as deletion of the sequence elements upstream of the splice donor site did not result in increased viral RNA and proteins. A computer-assisted analysis of the leader sequence of viral RNA shows it to be rich in secondary structure, which was markedly altered in the deletion mutants. Thus, the leader sequence of HIV-2 between the splice donor site and the gag ATG has at least two regulatory functions: one positive, affecting encapsidation, and the other negative, regulating virus expression. Because there is only a limited sequence or structural homology between the corresponding region of HIV-1 and HIV-2, they are likely to differ in their pathways regulating packaging and gene expression. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NR 41 TC 26 Z9 26 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 FEB PY 1995 VL 6 IS 2 BP 177 EP 184 DI 10.1089/hum.1995.6.2-177 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA QG730 UT WOS:A1995QG73000007 PM 7734518 ER PT J AU CAMA, A SIERRA, MD KADOWAKI, T KADOWAKI, H QUON, MJ RUDIGER, HW DREYER, M TAYLOR, SI AF CAMA, A SIERRA, MD KADOWAKI, T KADOWAKI, H QUON, MJ RUDIGER, HW DREYER, M TAYLOR, SI TI 2 MUTANT ALLELES OF THE INSULIN-RECEPTOR GENE IN A FAMILY WITH A GENETIC FORM OF INSULIN-RESISTANCE - A 10-BASE-PAIR DELETION IN EXON-1 AND A MUTATION SUBSTITUTING SERINE FOR ASPARAGINE-462 SO HUMAN GENETICS LA English DT Article ID TYROSINE KINASE DOMAIN; LDL RECEPTOR; ACANTHOSIS NIGRICANS; CULTURED LYMPHOCYTES; BINDING; EXPRESSION; PATIENT; HORMONE; WOMAN; SITES AB Mutations in the insulin receptor gene cause several genetic syndromes associated with extreme insulin resistance. We have studied three insulin resistant siblings with acanthosis nigricans, dental abnormalities, and acral hypertrophy. The female patient also had primary amenorrhea due to hyperandrogenism. All three patients were compound heterozygotes with two mutant alleles of the insulin receptor gene. One allele had a 10-bp deletion in the region of exon 1 encoding the hydrophobic signal peptide; this leads to a frameshift and premature chain termination at codon 61. The deletion occurs at the site of a direct repeat of a hexanucleotide sequence interrupted by a tetranucleotide sequence; the deletion may have resulted from recombination between the upstream and downstream hexanucleotide repeats. In the other mutant allele, there is a missense mutation substituting serine for Asn(462) - a mutation identified previously in one allele of the insulin receptor gene in a patient with type-A insulin resistance. The Ser(462) mutation impaired the ability of acidic pH to dissociate insulin from the receptor. Thus, like the previously described Glu(460) mutation, the Ser(462) mutation may retard dissociation of insulin from the receptor in the acidic compartment of the endosome and may, as a result, accelerate the rate of receptor degradation. C1 NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. UNIV G DANNUNZIO,FAC MED & CHIRURG,IST PATOL UMANA & MED SOCIALE,CHIETI,ITALY. ASAHI LIFE FDN,INST DIABET CARE & RES,TOKYO,JAPAN. UNIV VIENNA,DEPT OCCUPAT MED,INTERNAL MED CLIN 4,VIENNA,AUSTRIA. KRANKENHAUS BETHANIEN,DEPT DIABET & METAB,W-2000 HAMBURG,GERMANY. RI Quon, Michael/B-1970-2008 NR 32 TC 17 Z9 18 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD FEB PY 1995 VL 95 IS 2 BP 174 EP 182 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA QD372 UT WOS:A1995QD37200006 PM 7860063 ER PT J AU BRENNAN, MB HOCHGESCHWENDER, U AF BRENNAN, MB HOCHGESCHWENDER, U TI SO MANY NEEDLES, SO MUCH HAY SO HUMAN MOLECULAR GENETICS LA English DT Editorial Material ID DNA FRAGMENTS; SELECTION; SEQUENCES; STRATEGY; REGIONS; PCR C1 NIMH, CLIN NEUROSCI BRANCH, MOLEC GENET UNIT, BETHESDA, MD 20892 USA. NR 18 TC 13 Z9 13 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD FEB PY 1995 VL 4 IS 2 BP 153 EP 156 DI 10.1093/hmg/4.2.153 PG 4 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA QH634 UT WOS:A1995QH63400002 PM 7757061 ER PT J AU KOSUGI, S VANDOP, C GEFFNER, ME RABL, W CAREL, JC CHAUSSAIN, JL MORI, T MERENDINO, JJ SHENKER, A AF KOSUGI, S VANDOP, C GEFFNER, ME RABL, W CAREL, JC CHAUSSAIN, JL MORI, T MERENDINO, JJ SHENKER, A TI CHARACTERIZATION OF HETEROGENEOUS MUTATIONS CAUSING CONSTITUTIVE ACTIVATION OF THE LUTEINIZING-HORMONE RECEPTOR IN FAMILIAL MALE PRECOCIOUS PUBERTY SO HUMAN MOLECULAR GENETICS LA English DT Article ID PROTEIN-COUPLED RECEPTORS; THYROTROPIN TSH RECEPTOR; 3RD CYTOPLASMIC LOOP; ADENYLYL CYCLASE; PHOSPHOINOSITIDE; SIGNAL; GENE; RHODOPSIN; HELICES; CELLS AB Familial male precocious puberty (FMPP) is a gonadotropin-independent disorder that is inherited in an autosomal dominant, male-limited pattern. A heterozygous mutation encoding substitution of Asp(578) with Gly in transmembrane helix 6 of the G protein-coupled receptor for luteinizing hormone (LHR) has been found in affected males from nine American FMPP families. Cells expressing the mutant LHR exhibit markedly increased cyclic adenosine monophosphate (cAMP) production in the absence of agonist, suggesting that autonomous Leydig cell activity in FMPP is caused by a constitutively activated LHR. We have now analyzed genomic DNA from affected males from six additional FMPP families. PCR was used to amplify a fragment of the LHR gene encoding amino acid residues 441-594. None of the six new samples contained the Asp(578)-->Gly mutation, as indicated by absence of digestion with Mspl. PCR products were then screened for heterozygous mutations using temperature-grad lent gel electrophoresis. DNA fragments from two of the patients migrated abnormally. Direct sequencing of PCR product from one affected German male revealed a heterozygous mutation (ATG-->ATA) encoding Met(571)-->Ile at the cytoplasmic end of helix 6, the same mutation that has been reported in another European FMPP kindred. Affected males in the second family had a novel Thr(577)-->Ile mutation (ACC-->ATC). Mutations in different portions of the LHR or in a different gene may be responsible for disease in the other FMPP kindreds. Agonist binding and functional coupling of the mutant receptors to the cAMP and inositol phosphate pathways were studied by transiently expressing them in COS-7 cells. Agonist affinity was unaffected by the mutations. Like the Asp(578)-->Gly mutant receptor, the two newly identified mutant receptors triggered agonist-independent production of cAMP, but not of inositol phosphates, suggesting that autonomous testosterone production in FMPP can be explained by constitutive activation of the cAMP pathway alone. C1 NIDDK,METAB DIS BRANCH,BETHESDA,MD 20892. KYOTO UNIV,SCH MED,DEPT LAB MED,KYOTO 60601,JAPAN. UNIV CALIF LOS ANGELES,MED CTR,DEPT PEDIAT,LOS ANGELES,CA 90024. TECH UNIV MUNICH,KINDERKLIN,D-80804 MUNICH,GERMANY. HOP ST VINCENT DE PAUL,SERV ENDOCRINOL PEDIAT,F-75014 PARIS,FRANCE. NR 42 TC 99 Z9 103 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD FEB PY 1995 VL 4 IS 2 BP 183 EP 188 DI 10.1093/hmg/4.2.183 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA QH634 UT WOS:A1995QH63400006 PM 7757065 ER PT J AU WEINBERG, CR BAIRD, DD WILCOX, AJ AF WEINBERG, CR BAIRD, DD WILCOX, AJ TI THE SEX OF THE BABY MAY BE RELATED TO THE LENGTH OF THE FOLLICULAR PHASE IN THE CONCEPTION CYCLE SO HUMAN REPRODUCTION LA English DT Article DE OVULATION; SEX RATIO; SEX SELECTION; SPERM TRANSPORT; TWINNING ID OVULATION; PREGNANCY; RATIO; SPERM AB In a prospective study of normal couples discontinuing contraception to begin a pregnancy, the days of ovulation were estimated by hormonal assay of daily urine specimens. No hormonal interventions were used. Length of the follicular phase (from onset of menses to ovulation) was found to be related to the sex of the baby among 133 pregnancies that survived to delivery. Conception cycles with short follicular phases (early ovulation) tended to produce boys, while those with long follicular phases tended to produce girls. This relationship is consistent with other data and could explain sex-related differences in the length of gestation and the observed excess of same-sex pairs among dizygotic twins. C1 NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. RP WEINBERG, CR (reprint author), NIEHS,STAT & BIOMATH BRANCH,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Wilcox, Allen/0000-0002-3376-1311; Baird, Donna/0000-0002-5544-2653 NR 17 TC 41 Z9 41 U1 0 U2 5 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD FEB PY 1995 VL 10 IS 2 BP 304 EP 307 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA QK346 UT WOS:A1995QK34600012 PM 7769053 ER PT J AU TAKEDA, S DORFMAN, NA ROBERTGUROFF, M NOTKINS, AL RANDO, RF AF TAKEDA, S DORFMAN, NA ROBERTGUROFF, M NOTKINS, AL RANDO, RF TI 2-PHASE APPROACH FOR THE EXPRESSION OF HIGH-AFFINITY HUMAN ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS IMMUNOGLOBULIN FAB DOMAINS IN ESCHERICHIA-COLI SO HYBRIDOMA LA English DT Article ID HUMAN MONOCLONAL-ANTIBODIES; HIV-1 INFECTION INVITRO; DEPENDENT ENHANCEMENT; TUMOR-LOCALIZATION; NEUTRALIZING ANTIBODIES; ENVELOPE GLYCOPROTEIN; CELLS; FRAGMENTS; BINDING; CHIMPANZEES AB We describe here a two-phase approach for the development of high-affinity human anti-HIV immunoglobulin Fab domains in a bacterial expression system, The first phase of this technique involves the generation of human hybridoma cell lines producing high-affinity antibodies (MAbs), Anti-HIV-1 human MAbs from peripheral blood lymphocytes (PBLs) were prepared from an HIV-1-seropositive patient and from an HIV-1-seronegative volunteer immunized with HIV-1 rgp160. One MAb (T15G1), derived from the blood of the seropositive donor, was specific for HIV-1 gp41, recognized gp41 on the surface of HIV-1-infected cells and bound this antigen with an apparent dissociation constant of 4 x 10(-10) M. A second MAb (M7B5), developed from the immunized volunteer, was specific for HIV-1 gp120 with a dissociation constant on the order of 8 x 10(-10) M, but was unable to recognize cell surface antigen, In the second phase of this technique the Fab domains of these two MAbs were molecularly cloned into a bacterial expression vector. mRNA was isolated from the M7B5 and T15G1 hybridoma cell lines and used as a template for the production of cDNA. The cDNA was amplified using the polymerase chain reaction (PCR) technique, and then fused, in frame, into a bacterial expression vector, The recombinant Fabs (rFabM7B5 and rFabT15G1) were expressed as dicistronic messages in bacteria using the IPTG-inducible lactose promoter (LacZ), DNA sequencing was used to define the gamma chain isotypes and the V-H and V-L chain gene usage, The binding specificities of rFabM7B5 and rFabT15G1 were indistinguishable from their respective intact MAbs, The dissociation constants for the rFabs were approximately 1.4 x 10(-9) M for rFabM7B5 and 2 x 10(-9) M for rFabT15G1, Our studies show that human Fab domains, which maintain their binding specificities and have high binding affinities for HIV, can be rescued from hybridoma cell lines and expressed in bacteria. C1 NIDR,ORAL MED LAB,BETHESDA,MD 20892. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NR 47 TC 8 Z9 9 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD FEB PY 1995 VL 14 IS 1 BP 9 EP 18 DI 10.1089/hyb.1995.14.9 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA QK340 UT WOS:A1995QK34000002 PM 7768538 ER PT J AU LIN, MC AF LIN, MC TI MOUSE MODEL WORKSHOP SO HYPERTENSION LA English DT Letter RP LIN, MC (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD FEB PY 1995 VL 25 IS 2 BP 302 EP 302 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA QE776 UT WOS:A1995QE77600026 ER PT J AU DAY, PM ESQUIVEL, F LUKSZO, J BENNINK, JR YEWDELL, JW AF DAY, PM ESQUIVEL, F LUKSZO, J BENNINK, JR YEWDELL, JW TI EFFECT OF TAP ON THE GENERATION AND INTRACELLULAR TRAFFICKING OF PEPTIDE-RECEPTIVE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I MOLECULES SO IMMUNITY LA English DT Article ID RMA-S CELLS; MONOCLONAL-ANTIBODIES; ENDOPLASMIC-RETICULUM; HEAVY-CHAINS; VIRAL PEPTIDES; T-CELLS; MHC; BETA-2-MICROGLOBULIN; BINDING; ANTIGENS AB Using a fluorescein-conjugated antigenic peptide, peptide-receptive H-2K(b) MHC class I molecules were found throughout the secretory pathways of RMA cells and peptide transporter (TAP)-deficient derivative cells (RMA/S). RMA/S cells displayed higher levels of intracellular peptide-receptive molecules, while, surprisingly, RMA cells expressed 3- to 5-fold more cell surface peptide-receptive molecules. Metabolic radiolabeling of K-b-associated oligosaccharides with [1-H-3]galactose demonstrated that despite a large difference in the fraction of K-b molecules in native conformation in detergent extracts, K-b transport rates from the trans-Golgi complex to the surfaces of RMA and RMA/S cells were similar. Thus, although considerable numbers of class I alpha chains reach the RM AIS cell surface, they are a less productive source of peptide-receptive molecules than class I molecules synthesized by TAP-expressing RMA cells, suggesting paradoxically that TAP functions to increase the amount of peptide-receptive molecules at the cell surface. C1 NIAID,BIOL RESOURCES BRANCH,BETHESDA,MD 20892. RP DAY, PM (reprint author), NIAID,VIRAL DIS LAB,BETHESDA,MD 20892, USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 58 TC 75 Z9 75 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD FEB PY 1995 VL 2 IS 2 BP 137 EP 147 DI 10.1016/S1074-7613(95)80014-X PG 11 WC Immunology SC Immunology GA QH132 UT WOS:A1995QH13200002 PM 7895170 ER PT J AU SEI, Y REICH, H AF SEI, Y REICH, H TI THAPSIGARGIN INDUCES IL-2 RECEPTOR ALPHA-CHAIN IN HUMAN PERIPHERAL AND JURKAT T-CELLS VIA A PROTEIN-KINASE C-INDEPENDENT MECHANISM SO IMMUNOLOGY LETTERS LA English DT Article DE IL-2 RECEPTOR; PHORBOL ESTER; T CELL; THAPSIGARGIN ID ATPASE INHIBITOR THAPSIGARGIN; INOSITOL PHOSPHATE; TUMOR PROMOTER; GENE-EXPRESSION; LYMPHOCYTES-T; CA2+ INFLUX; INTERLEUKIN-2; ACTIVATION; MOBILIZATION; TRANSCRIPTION AB Thapsigargin (TG), an inhibitor of Ca2+-ATPase, depletes intracellular Ca2+ stores and induces a sustained Ca2+ influx without altering phosphatidyl inositol levels. TG plus phorbol myristate acetate (PMA) but not TG alone induced IL-2 in Jurkat T cells, suggesting that TG had no effect on protein kinase C (PKC). However, TG induced increases in IL-2R alpha protein as well as IL-2R alpha mRNA in Jurkat T cells in a dose-dependent manner. A similar increase in IL-2R alpha by TG was also observed in human peripheral T cells. Further, like PMA, TG markedly induced NF kappa B in Jurkat T cells. However, TG and PMA exhibited a synergistic action on IL-2R alpha expression, suggesting that TG and PMA induce IL-2R alpha through distinct pathways. PMA- but not TG-induced IL-2R alpha is inhibited by the PKC inhibitor H7, whereas TG- but not PMA-induced IL-2R alpha was inhibited by cholera toxin, forskolin and 1,9-dideoxy forskolin. In tote, these results suggest that TG induces IL-2R alpha in human T cells through a PKC-independent pathway. RP SEI, Y (reprint author), NIDDK,NEUROSCI LAB,BLDG 8,ROOM 111,BETHESDA,MD 20892, USA. NR 33 TC 11 Z9 11 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD FEB PY 1995 VL 45 IS 1-2 BP 75 EP 80 DI 10.1016/0165-2478(94)00250-U PG 6 WC Immunology SC Immunology GA QT191 UT WOS:A1995QT19100013 PM 7622191 ER PT J AU BONOMO, A KEHN, PJ SHEVACH, EM AF BONOMO, A KEHN, PJ SHEVACH, EM TI POST-THYMECTOMY AUTOIMMUNITY - ABNORMAL T-CELL HOMEOSTASIS SO IMMUNOLOGY TODAY LA English DT Article ID NEONATAL THYMECTOMY; CLONAL DELETION; SELF-TOLERANCE; ADULT THYMUS; B-CELLS; MICE; DISEASE; OOPHORITIS; EXPRESSION; REQUIREMENT AB Thymectomy of 3-day-old mice induces organ-specific autoimmune disease, which is characterized by the presence of autoantibodies and T-cell infiltrates in the affected organs. Here, Adriana Bonomo and colleagues propose a new model for the pathogenesis of this syndrome, which integrates many of the homeostatic mechanisms of the immune system, including central and peripheral tolerance, T-cell maturation and exportation from the thymus, as well as lymphocyte recirculation and homing. RP BONOMO, A (reprint author), NIAID,IMMUNOL LAB,CELLULAR IMMUNOL SECT,BLDG 10,BETHESDA,MD 20892, USA. NR 33 TC 80 Z9 81 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD FEB PY 1995 VL 16 IS 2 BP 61 EP 67 DI 10.1016/0167-5699(95)80089-1 PG 7 WC Immunology SC Immunology GA QE596 UT WOS:A1995QE59600004 PM 7888068 ER PT J AU LUSSO, P GALLO, RC AF LUSSO, P GALLO, RC TI HUMAN HERPESVIRUS-6 IN AIDS SO IMMUNOLOGY TODAY LA English DT Article ID VIRUS TYPE-1 REPLICATION; MARROW TRANSPLANTATION; INFECTION; CELLS; CD4; INDUCTION; RECEPTOR; HHV-6; PNEUMONITIS; RETROVIRUS AB Multiple lines of clinical and experimental evidence suggest that human herpesvirus 6 (HHV-6) may act as an accelerating factor in the natural history of human immunodeficiency virus (HIV) infection. Although, in common with HIV HHV-6 has a primary tropism for CD4(+) T cells, its potential effects on the immune system are broader. For instance, HHV-6 can also infect and kill CD8(+) T cells, natural killer cells and mononuclear phagocytes. Here, Paolo Lusso and Robert Gallo suggest that understanding the immunopathogenic role of HHV-6 in the course of HIV infection may shed new light on the complex mechanisms of disease progression in AIDS. RP NCI, TUMOR CELL BIOL LAB, BLDG 37, BETHESDA, MD 20892 USA. NR 41 TC 122 Z9 125 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD FEB PY 1995 VL 16 IS 2 BP 67 EP 71 DI 10.1016/0167-5699(95)80090-5 PG 5 WC Immunology SC Immunology GA QE596 UT WOS:A1995QE59600005 PM 7888069 ER PT J AU EGAN, AF CHAPPEL, JA BURGHAUS, PA MORRIS, JS MCBRIDE, JS HOLDER, AA KASLOW, DC RILEY, EM AF EGAN, AF CHAPPEL, JA BURGHAUS, PA MORRIS, JS MCBRIDE, JS HOLDER, AA KASLOW, DC RILEY, EM TI SERUM ANTIBODIES FROM MALARIA-EXPOSED PEOPLE RECOGNIZE CONSERVED EPITOPES FORMED BY THE 2 EPIDERMAL GROWTH-FACTOR MOTIFS OF MSP1(19), THE CARBOXY-TERMINAL FRAGMENT OF THE MAJOR MEROZOITE SURFACE PROTEIN OF PLASMODIUM-FALCIPARUM SO INFECTION AND IMMUNITY LA English DT Article ID MOLECULAR-WEIGHT PRECURSOR; MONOCLONAL-ANTIBODIES; SYNTHETIC PEPTIDES; AOTUS MONKEYS; ANTIGEN; RECOMBINANT; PARASITE; IMMUNIZATION; INVASION; YOELII AB The major merozoite surface protein of Plasmodium falciparum (PfMSP1) is a candidate antigen for a malaria vaccine. A 19-kDa C-terminal processing product of PfMSP1 (PfMSP1(19)) is composed of two domains sharing a cysteine-rich motif with epidermal growth factor (EGF) and is the target of monoclonal antibodies which block erythrocyte invasion in vitro. We have evaluated human antibody responses to PfMSP1(19) by using recombinant proteins representing the EGF motifs encoded by the two main alleles of the MSPI gene. We find that both EGF motifs are antigenic but that only 10 to 20% of malaria exposed individuals have serum antibodies that recognized either of the motifs. When both EGF motifs were expressed together as a single protein, they were recognized by more than 40% of sera from malaria-exposed individuals. Major epitopes recognized by human antibodies are dependent upon the correct tertiary structure of the protein and are cross-reactive between the different allelic sequences of PfMSP1(19). This suggests that antibodies induced by vaccination with one or the other allelic forms of the protein could recognize all strains of P. falciparum. Immunoglobulin G (IgG) subclass-specific enzyme immunoassays indicate that PfMSP1(19) antibodies are predominantly of the IgG1 subclass. C1 UNIV EDINBURGH,DIV BIOL SCI,INST CELL ANIM & POPULAT BIOL,EDINBURGH EH9 3JT,MIDLOTHIAN,SCOTLAND. NATL INST MED RES,DIV PARASITOL,LONDON NW7 1AA,ENGLAND. LONDON SCH HYG & TROP MED,DEPT EPIDEMIOL & POPULAT SCI,LONDON WC1,ENGLAND. NIAID,MALARIA RES LAB,BETHESDA,MD 20892. RI Holder, Anthony/A-7554-2013; Riley, Eleanor/C-8960-2013 OI Holder, Anthony/0000-0002-8490-6058; Riley, Eleanor/0000-0003-3447-3570 FU Medical Research Council [MC_U117532067]; Wellcome Trust NR 36 TC 121 Z9 125 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD FEB PY 1995 VL 63 IS 2 BP 456 EP 466 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA QC603 UT WOS:A1995QC60300013 PM 7822010 ER PT J AU NAKANISHI, K YOSHIMOTO, T CHU, CC MATSUMOTO, H HASE, K NAGAI, N TANAKA, T MIYASAKA, M PAUL, WE SHINKA, S AF NAKANISHI, K YOSHIMOTO, T CHU, CC MATSUMOTO, H HASE, K NAGAI, N TANAKA, T MIYASAKA, M PAUL, WE SHINKA, S TI IL-2 INHIBITS IL-4-DEPENDENT IGE AND IGG1 PRODUCTION IN-VITRO AND IN-VIVO SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE DIGESTION CIRCULARIZATION POLYMERASE CHAIN REACTION; IGE INHIBITION; IGG1 INHIBITION; IL-2; IL-2R-BETA; IL-4; S-MU-S-GAMMA-1 SWITCHING ID STIMULATORY FACTOR-I; MURINE B-CELLS; RECEPTOR GAMMA-CHAIN; MONOCLONAL-ANTIBODY; T-CELLS; DIFFERENTIATION FACTORS; INTERLEUKIN-2 IL-2; INTERFERON-GAMMA; LYMPHOMA LINE; BETA-CHAIN AB Nippostrongylus brasiliensis (Nb) infection of mice induces IL-4 producing CD4(+) T cells which stimulate polyclonal IgE and IgG1 production, providing a model system to study IL-4 action on a cells in vivo. B cell la expression and the proportion of IL-2R beta positive B cells were increased in Nb-inoculated mice, and B cells from these mice responded to IL-2 by prompt and marked cell growth. Injection of anti-IL-4 1 day after Nb inoculation substantially inhibited these responses, indicating that they were largely IL-4 dependent. Thus IL-4 acted as a polyclonal a cell activator in vivo and caused a cells to develop into IL-2 responsive cells. Furthermore, injection of IL-2 inhibited IgG1 and IgE production by Nb-inoculated mice. To understand the mechanism of this IL-2-mediated inhibition, we used an in vitro IgG1 and IgE induction system. B cells from Nb-inoculated mice displayed an increase in the capacity of IL-2 to inhibit lipopolysaccharide (LPS) plus IL-4-driven IgE and IgG1 production, indicating that B cells expressing IL-PRP are highly sensitive to IL-2. This inhibition was principally dependent upon the direct action of IL-2 on a cells. However, partial abolition of IL-2 inhibitory action by anti-IFN-gamma treatment suggested that endogenous IFN-gamma released from IL-2-stimulated cells was also involved in this IL-2-mediated IgE and IgG1 inhibition. Northern blot analysis demonstrated that IL-2 inhibited IL-4 induction of germline and productive C-epsilon transcripts in LPS-stimulated a cells. Digestion-circularization polymerase chain reaction analysis revealed IL-2 inhibited IL-4 induction of s mu-s gamma 1 rearrangement in LPS-stimulated B cells. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. OSAKA UNIV,SCH MED,BIOMED RES CTR,DEPT BIOREGULAT,SUITA,OSAKA 565,JAPAN. RP NAKANISHI, K (reprint author), HYOGO MED UNIV,DEPT IMMUNOL & MED ZOOL,NISHINOMIYA,HYOGO 663,JAPAN. RI Tanaka, Toshiyuki/D-1193-2010 NR 44 TC 11 Z9 11 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD FEB PY 1995 VL 7 IS 2 BP 259 EP 268 DI 10.1093/intimm/7.2.259 PG 10 WC Immunology SC Immunology GA QH585 UT WOS:A1995QH58500013 PM 7734421 ER PT J AU DEUTSCH, D PALMON, A DAFNI, L CATALANOSHERMAN, J YOUNG, MF FISHER, LW AF DEUTSCH, D PALMON, A DAFNI, L CATALANOSHERMAN, J YOUNG, MF FISHER, LW TI THE ENAMELIN (TUFTELIN) GENE SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE ENAMEL; TUFTELIN; GENE; CHROMOSOMAL LOCALIZATION; MINERALIZATION ID LINKED AMELOGENESIS IMPERFECTA; AMINO-ACID-COMPOSITION; RAT INCISOR; MATRIX PROTEINS; IMMUNOHISTOCHEMICAL LOCALIZATION; MATURATION STAGE; BOVINE ENAMEL; FETAL ENAMEL; TOOTH ENAMEL; AMELOBLASTS AB This paper reviews the primary structure, characteristics and possible function of tuftelin/enamelin protein. It describes the distribution of tuftelin in the ameloblast cell and in the extracellular enamel matrix, employing high resolution protein-A gold immunocytochemistry. The chromosomal localization of the human tuftelin gene and its possible involvement in autosomally linked Amelogenesis Imperfecta, the most common hereditary disease of enamel, is also discussed. C1 NIDR, BONE RES BRANCH, BETHESDA, MD 20892 USA. RP DEUTSCH, D (reprint author), HEBREW UNIV JERUSALEM, HADASSAH FAC DENT MED, DEPT ORAL BIOL, DENT RES UNIT, BOX 1172, JERUSALEM, ISRAEL. NR 83 TC 41 Z9 42 U1 0 U2 0 PU U B C PRESS PI BILBAO PA UNIV BASQUE COUNTRY, EDITORIAL SERVICES, PO BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PD FEB PY 1995 VL 39 IS 1 BP 135 EP 143 PG 9 WC Developmental Biology SC Developmental Biology GA QR862 UT WOS:A1995QR86200012 PM 7626400 ER PT J AU BYERS, MR MECIFI, KB IADAROLA, MJ AF BYERS, MR MECIFI, KB IADAROLA, MJ TI FOCAL C-FOS EXPRESSION IN DEVELOPING RAT MOLARS - CORRELATIONS WITH SUBSEQUENT INTRADENTAL AND EPITHELIAL SENSORY INNERVATION SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE ODONTOBLASTS; AMELOBLASTS; JUNCTIONAL EPITHELIUM; CGRP; FOS ID NERVE GROWTH-FACTOR; PROGRAMMED CELL-DEATH; GENE-RELATED PEPTIDE; FACTOR RECEPTOR; PROTO-ONCOGENE; NGF RECEPTOR; SPINAL-CORD; DENTIN; TOOTH; TEETH AB The purpose of this study was to analyze the temporal and spatial patterns of expression of the inducible transcription protein Fos and the Fos-related antigens (Fra) in developing rat teeth. Immunoreactivity (IR) for Fos/Fra was analyzed at postnatal ages 1-35 days. A transient gradient of Fos/Fra-IR was found in all the molars in the coronal odontoblasts along sites of dentinogenesis, with numerous cells and intense staining near the pulp horn tip, and fewer cells and less staining in mid-crown and cervical pulp. This gradient was well established in first molars of the one day old rats; it was first seen in second molars in the 2 day old rats; and it was found in third molars at 10 days. The Fos/Fra-IR was transient and faded after a few days. Rat molars have a tilted orientation so that maxillary molar crown cusps point in a posterior direction and mandibular crowns in the anterior direction. In each set of molars dentinogenesis was initiated along the side of each pulp horn closest to the gingival surface, i.e. anterior for maxillary crowns and posterior for mandibular crowns; and the Fos/Fra-IR first appeared next to those asymmetric sites. As the wave of dentinogenesis spread around the crown, it was accompanied by odontoblastic expression of Fos/Fra-IR that had decreasing intensity in mid- and cervical crown. Molar root pulp lacked Fos/Fra-IR, and incisor teeth only had odontoblastic and ameloblastic immunoreactivity in the 1 day old rats. Dentinal innervation developed in molars two weeks after the transient Fos/Fra, and it established a similar gradient that was most dense near the crown tips on anterior sides of maxillary molars and posterior sides of mandibular molars. The non-secretory pre-ameloblast epithelium at the molar enamel-free cusp tips also had prolonged Fos/Fra-IR during crown morphogenesis at the enamel-free cusp tips. Sensory innervation was concentrated there prior to eruption, and junctional epithelium appeared to originate from those cells during eruption. The Fos/Fra-IR in developing rat molar odontoblasts and ameloblasts had distinct sites of prolonged expression during crown morphogenesis that did not appear to involve apoptosis, and that matched later sites of sensory innervation. C1 UNIV WASHINGTON, DEPT BIOL STRUCT, SEATTLE, WA 98195 USA. UNIV WASHINGTON, DEPT ENDODONT, SEATTLE, WA 98195 USA. NIDR, NEUROBIOL & ANESTHESIA BRANCH, BETHESDA, MD 20892 USA. RP BYERS, MR (reprint author), UNIV WASHINGTON, DEPT ANESTHESIOL, BOX 356540, SEATTLE, WA 98195 USA. FU NIDCR NIH HHS [DE05159] NR 54 TC 11 Z9 11 U1 0 U2 0 PU U B C PRESS PI BILBAO PA UNIV BASQUE COUNTRY, EDITORIAL SERVICES, PO BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PD FEB PY 1995 VL 39 IS 1 BP 181 EP 189 PG 9 WC Developmental Biology SC Developmental Biology GA QR862 UT WOS:A1995QR86200017 PM 7626405 ER PT J AU SHU, XO CLEMENS, J ZHENG, W YING, DM JI, BT JIN, F AF SHU, XO CLEMENS, J ZHENG, W YING, DM JI, BT JIN, F TI INFANT BREAST-FEEDING AND THE RISK OF CHILDHOOD LYMPHOMA AND LEUKEMIA SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article ID CANCER; EPIDEMIOLOGY AB Background. A protective effect of breastfeeding on childhood lymphoma has been indicated but supportive evidence is limited. Method. Data from a population-based case-control study of childhood cancer in Shanghai, including 82 lymphoma cases and 159 acute leukaemia cases and their age- and sex-matched community controls, were analysed. Results. After adjustment for potentially confounding variables, a slight, although non-significant, reduction in risk of lymphoma was observed among children who were breastfed as infants Versus those who were not (odds ratio [OR] = 0.69; 95% Cl : 0.3-1.7). The reduction was somewhat greater for children who had been breastfed longer and appeared to pertain primarily to Hodgkin's disease and to cases diagnosed before the age of 6 years. As expected, there was no. reduction in risk of acute leukaemia associated with breastfeeding. Conclusions. Although providing neither strong support for nor refuting the study hypothesis, these data suggest that if breastfeeding does reduce the risk of lymphoma, its protective effect among Chinese children is likely modest in magnitude and concentrated in certain subgroups defined by length of breastfeeding, age at diagnosis and histological subtype of cancer. C1 NICHHD,EPIDEMIOL BRANCH,BETHESDA,MD 20892. UNIV MINNESOTA,SCH MED,DEPT PEDIAT,DIV PEDIAT EPIDEMIOL CLIN RES,MINNEAPOLIS,MN 55455. XING HUA HOSP,SHANGHAI,PEOPLES R CHINA. RP SHU, XO (reprint author), SHANGHAI CANC INST,DEPT EPIDEMIOL,SHANGHAI,PEOPLES R CHINA. NR 12 TC 45 Z9 45 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD FEB PY 1995 VL 24 IS 1 BP 27 EP 32 DI 10.1093/ije/24.1.27 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QR855 UT WOS:A1995QR85500004 PM 7797353 ER PT J AU VOGEL, FR AF VOGEL, FR TI THE ROLE OF ADJUVANTS IN RETROVIRAL VACCINES SO INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 5th International Conference on Immunopharmacology CY MAY 29-JUN 02, 1994 CL PRAGUE, CZECH REPUBLIC DE ADJUVANTS; IMMUNOLOGICAL; HIV; SIV ID RECOMBINANT GAMMA-INTERFERON; IMMUNOLOGICAL ADJUVANTS; ANTIBODY-RESPONSE; CHOLERA-TOXIN; VIRUS-VACCINE; CELL SUBSETS; IMMUNIZATION; LIPOSOMES; MICE; INDUCTION AB The global HIV epidemic continues unchecked. Reports to the World Health Organization's Global Programme on AIDS indicate that more than 14 million persons have become infected with HIV and more than two million have died with AIDS. The spread of AIDS has generated a worldwide mandate for the development of safe and effective vaccines against HIV. Vaccines have been the most effective defense against other viral diseases such as polio and smallpox. However, the development of a vaccine against HIV-1 is a formidable task due to the variation of the virus, inadequate animal models of HIV disease, and the lack of correlates of protective immunity. Several candidate HIV vaccines are composed of synthetic, recombinant, or highly purified subunit antigens. Vaccines composed of subunit antigens generally are considered to be safer than traditional whole-killed or live-attenuated vaccines. However, purified subunit vaccines often are inherently less immunogenic than traditional vaccines. Immunologic adjuvants are agents that act generally to enhance specific immune responses to vaccine antigens. Formulation of experimental HIV vaccines with potent immunologic adjuvants is an attractive approach for amplifying and directing immune responses to highly purified antigens. Alum adjuvants, consisting of aluminum salts, first described in the 1920s, remain the only adjuvants in U.S.-licensed vaccine formulations. Novel adjuvants now undergoing preclinical and clinical testing with experimental subunit Vaccines include detoxified lipid A, adjuvant emulsions, liposomes, biodegradable microspheres, muramyl peptides, and saponins. Adjuvants have been shown to elicit cytotoxic T-cell responses as well as antibody to subunit antigens. Some of these adjuvants also have been shown to lower the threshold levels of antigen necessary to evoke immune responses. This review will describe several types of immunological adjuvants now being evaluated in experimental retroviral vaccines and mechanisms of their adjuvanticity, Initial steps being taken toward the standardization of adjuvant safety testing will also be discussed. RP VOGEL, FR (reprint author), NIAID,DIV AIDS,VACCINE & PREVENT RES PROGRAM,BETHESDA,MD 20892, USA. NR 43 TC 20 Z9 20 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0192-0561 J9 INT J IMMUNOPHARMACO JI Int. J. Immunopharmacol. PD FEB PY 1995 VL 17 IS 2 BP 85 EP 90 DI 10.1016/0192-0561(94)00095-6 PG 6 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA QW230 UT WOS:A1995QW23000004 PM 7657411 ER PT J AU SUN, Y DONG, ZG JACKMAN, J HEGAMYER, G KIM, H COLBURN, NH AF SUN, Y DONG, ZG JACKMAN, J HEGAMYER, G KIM, H COLBURN, NH TI STATUS OF THE MDM-2 AND WAF-1 GENES IN MOUSE EPIDERMAL JB6 VARIANTS HARBORING WILD-TYPE P53 - A P53-INDEPENDENT INDUCTION OF WAF-1 SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE TUMOR PROMOTION PROGRESSION POINT MUTATION; MDM-2/WAF-1 EXPRESSION; MESSENGER-RNA TRANSCRIPTS; TPA/TNF-ALPHA REGULATION; APOPTOSIS ID TUMOR SUPPRESSOR GENE; TRANSACTIVATION; MUTATIONS; PROTEIN; PROGRESSION; EXPRESSION; INHIBITOR; PROMOTER; KINASES; SKIN AB Mutational inactivation of the p53 tumor suppressor gene has been found not to be involved in preneoplastic-to-neoplastic progression in mouse JB6 variants. To examine the role of an inactivated p53 pathway in this tumor promotion/progression model, we have studied the possible alteration of the MDM-2 oncogene, a gene whose product binds to and inactivates p53, and WAF-1 tumor suppressor gene, a gene transcriptionally controlled by p53 that mediates p53 tumor suppression. Alteration of either of these two genes might mimic p53 inactivation in cells expressing wild-type p53. Northern analysis revealed that MDM-2 expression was, in general, upregulated in neoplastic JB6 cells as compared with preneoplastic cells. This higher expression was not due to the gene amplification. Mutational analysis of WAF-1 revealed a) no point mutation in neoplastic cells; b) two polymorphic sites; and c) three nucleotide disagreements with the published sequence. Expression of the WAF-1 gene was also found to be, in general, higher in neoplastic cells, and induced by TPA and/or TNF-alpha in a p53-independent manner. The overall induced level of WAF-1 mRNA was higher in apoptosis sensitive cells after TPA/TNF-alpha treatment, suggesting a role of WAF-1 in mediating apoptosis. We conclude from this study that a) there is no evidence for mutational inactivation of WAF-1 that might mimic p53 inactivation in the JB6 model; b) elevated expression of MDM-2 and/or WAF-1 might be involved in neoplastic progression; and c) there is a p53-independent pathway controlling WAF-1 expression which may mediate p53-independent apoptosis. C1 NCI,VIRAL CARCINOGENESIS LAB,CELL BIOL SECT,FREDERICK,MD. FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,CTR BIOL CARCINOGENESIS & DEV,FREDERICK,MD. GEORGETOWN UNIV,SCH MED,DEPT BIOCHEM & MOLEC BIOL,WASHINGTON,DC. NR 36 TC 8 Z9 8 U1 0 U2 1 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD FEB PY 1995 VL 6 IS 2 BP 465 EP 471 PG 7 WC Oncology SC Oncology GA QD772 UT WOS:A1995QD77200026 PM 21556561 ER PT J AU BALBONI, G SALVADORI, S DANGELI, F MARCHETTI, P LAZARUS, LH BRYANT, SD BIANCHI, C AF BALBONI, G SALVADORI, S DANGELI, F MARCHETTI, P LAZARUS, LH BRYANT, SD BIANCHI, C TI SINGLE DIASTEREOMERIC DESAMINOTYROSYLALANYL TETRAPEPTIDES AND HEPTAPEPTIDES WITH OPIOID ANTAGONISTIC ACTIVITY SO INTERNATIONAL JOURNAL OF PEPTIDE AND PROTEIN RESEARCH LA English DT Article DE AMINODICARBOXYLIC ACIDS; ANTAGONISTS; OPIOID PEPTIDES; OPIOID RECEPTORS; PSEUDOPEPTIDES ID MOUSE VAS-DEFERENS; RECEPTOR ANTAGONISTS; PHARMACOLOGICAL ACTIVITY; METHIONINE-ENKEPHALIN; HIGHLY POTENT; HIGH-AFFINITY; PEPTIDE-BOND; ANALOGS; BINDING; SELECTIVITY AB The N-terminal dipeptide Tyr-D-Ala of a mu-selective agonist, dermorphin tetrapeptide (DT, H-Tyr-D-Ala-Phe-Gly-NH2) and delta-selective agonist deltorphin C (DEL-C, H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2) was changed into an aminodiacyl moiety. The relevant synthetic step is a nucleophilic substitution of bromine from a chiral 2-bromopropanamide by the amino group of tyrosine, with overall retention of configuration. The resulting pseudo tetra- and heptapeptides I-VI were characterized for mu- and delta-opioid receptor binding properties using [H-3]DAGO and [H-3]DPDPE, respectively, and in a bioassay using guinea pig ileum (GPI) and mouse vas deferens (MVD). As a result of chemical alteration of N-terninal dipeptide moiety, all syn thesized analogs showed considerable reduction in opioid receptor affinity compared to mu- and delta-prototypes (500-fold on the mu-site, analog I, and 125-fold on the delta-site, analog IV). Interestingly, analogs I and IV showed moderate antagonist activity, respectively, on GPI and MVD, with pA(2) values of 6.05 and 6.82. Analog IV did not exhibit the delta-antagonist potency and delta-selectivity of TIPP peptides. (C) Munksgaard 1995. C1 UNIV FERRARA,INST PHARMACOL,I-44100 FERRARA,ITALY. NIEHS,PEPTIDE NEUROCHEM SECT,RES TRIANGLE PK,NC 27709. RP BALBONI, G (reprint author), UNIV FERRARA,DEPT PHARMACEUT SCI,VIA FOSSATO MORTARA 17-19,I-44100 FERRARA,ITALY. NR 49 TC 3 Z9 3 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0367-8377 J9 INT J PEPT PROT RES JI Int. J. Pept. Protein Res. PD FEB PY 1995 VL 45 IS 2 BP 187 EP 193 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QJ774 UT WOS:A1995QJ77400014 PM 7782167 ER PT J AU GILSTRAP, LC CHRISTENSEN, R CLEWELL, WH DALTON, ME DAVIDSON, EC ESCOBEDO, MB GJERDINGEN, DK GODDARDFINEGOLD, J GOLDENBERG, RK GRIMES, DA HANSEN, TN KAUFFMAN, RE KEELER, EB OH, W SUSMAN, EJ VOGEL, MG AVERY, ME BALLARD, PL BALLARD, RA CROWLEY, P GARITE, T GOLDENBERG, RL HANKINS, GDV JOBE, AH KOPPE, JG MAHER, JE MERKATZ, IR SHANKARAN, S SIMPSON, KN SINCLAIR, JC SLOTKIN, TA TAEUSCH, HW WRIGHT, LL ALEXANDER, D BERBERICH, MA BRACKEN, M COOPER, L CULPEPPER, L ELLIOTT, JM FERGUSON, JH FRIGOLETTO, F GAIL, DB HALL, WH JONES, MD MEDOFFCOOPER, B MERENSTEIN, GB WHALEN, JM AF GILSTRAP, LC CHRISTENSEN, R CLEWELL, WH DALTON, ME DAVIDSON, EC ESCOBEDO, MB GJERDINGEN, DK GODDARDFINEGOLD, J GOLDENBERG, RK GRIMES, DA HANSEN, TN KAUFFMAN, RE KEELER, EB OH, W SUSMAN, EJ VOGEL, MG AVERY, ME BALLARD, PL BALLARD, RA CROWLEY, P GARITE, T GOLDENBERG, RL HANKINS, GDV JOBE, AH KOPPE, JG MAHER, JE MERKATZ, IR SHANKARAN, S SIMPSON, KN SINCLAIR, JC SLOTKIN, TA TAEUSCH, HW WRIGHT, LL ALEXANDER, D BERBERICH, MA BRACKEN, M COOPER, L CULPEPPER, L ELLIOTT, JM FERGUSON, JH FRIGOLETTO, F GAIL, DB HALL, WH JONES, MD MEDOFFCOOPER, B MERENSTEIN, GB WHALEN, JM TI EFFECT OF CORTICOSTEROIDS FOR FETAL MATURATION ON PERINATAL OUTCOMES SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article AB Objective.-To develop a consensus on the use of antenatal corticosteroids for fetal maturation in preterm infants. Participants.-A nonfederal, nonadvocate, 16-member consensus panel including representatives from neonatology, obstetrics, family medicine, behavioral medicine, psychology, biostatistics, and the public; 19 experts in neonatology, obstetrics, and pharmacology presented data to the consensus panel and a conference audience of approximately 500. Evidence.-An extensive bibliography of references was produced for the consensus panel and the conference audience using a variety of on-line databases including MEDLINE. The consensus panel met several times prior to the conference to review the literature. It also commissioned an updated meta-analysis, a neonatal registry review, and an economic analysis that were presented at the conference. The experts prepared abstracts for distribution at the conference, presented data, and answered questions from the panel and audience. The panel evaluated the strength of the scientific evidence using the grading system developed by the Canadian Task Force on the Periodic Health Examination and adapted by the US Preventive Services Task Force, Consensus.-The consensus panel, answering predefined consensus questions, developed their conclusions based on the scientific evidence presented in open forum and the scientific literature. Consensus Statement.-The consensus panel composed a draft statement that was read in its entirety at the conference for comment. The panel released a revised statement at the end of the conference and finalized the revisions a few weeks after the conference. Conclusions.-Antenatal corticosteroid therapy is indicated for women at risk of premature delivery with few exceptions and will result in a substantial decrease in neonatal morbidity and mortality, as well as substantial savings in health care costs, The use of antenatal corticosteroids for fetal maturation is a rare example of a technology that yields substantial cost savings in addition to improving health. C1 UNIV FLORIDA,COLL MED,GAINESVILLE,FL. PHOENIX PERINATAL ASSOCIATES,DEPT MATERNAL FETAL MED,PHOENIX,AZ. TUFTS UNIV,NEW ENGLAND MED CTR,DEPT OBSTET & GYNECOL,BOSTON,MA 02111. MARTIN LUTHER KING JR CHARLES R DREW UNIV,LOS ANGELES,CA. UNIV TEXAS,HLTH SCI CTR,DIV NEONATOL,SAN ANTONIO,TX. UNIV MINNESOTA,DEPT FAMILY PRACTICE & COMMUNITY HLTH,ST PAUL,MN 55108. BAYLOR COLL MED,DEPT PEDIAT & PATHOL,DIV PEDIAT NEUROL,HOUSTON,TX 77030. UNIV ALABAMA,SCH MED,CTR OBSTET RES,BIRMINGHAM,AL. UNIV ALABAMA,SCH MED,DEPT OBSTET & GYNECOL,BIRMINGHAM,AL. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. WAYNE STATE UNIV,CHILDRENS HOSP MICHIGAN,DEPT PEDIAT & PHARMACOL,DETROIT,MI. RAND CORP,DEPT SOCIAL POLICY,SANTA MONICA,CA 90406. BROWN UNIV,WOMEN & INFANTS HOSP,SCH MED,DEPT PEDIAT,PROVIDENCE,RI. PENN STATE UNIV,BIOBEHAV HLTH PROGRAM,UNIVERSITY PK,PA 16802. SCH DIST HATBORO HORSHAM,ELKINS PK,PA. NICHHD,BETHESDA,MD 20892. UNIV PENN,SCH MED,DEPT PEDIAT,DIV NEONATOL,PHILADELPHIA,PA 19104. CHILDRENS HOSP PHILADELPHIA,PHILADELPHIA,PA 19104. NHLBI,DIV LUNG DIS,CELL & DEV BIOL BRANCH,BETHESDA,MD 20892. YALE UNIV,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT 06520. NINR,DIV EXTRAMURAL PROGRAMS,BETHESDA,MD. BROWN UNIV,MEM HOSP RHODE ISL,DEPT FAMILY MED,PAWTUCKET,RI 02860. NIH,OFF MED APPLICAT RES,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,VINCENT MEM HOSP,DIV OBSTET,BOSTON,MA 02114. UNIV TEXAS,SW MED CTR,DEPT OBSTET & GYNECOL,DALLAS,TX 75235. UNIV CALIF LOS ANGELES,HARBOR MED CTR,SCH MED,WALTER P MARTIN RES CTR,TORRANCE,CA 90509. UNIV COLORADO,SCH MED,DEPT PEDIAT,DENVER,CO. CHILDRENS HOSP,DENVER,CO 80218. UNIV PENN,SCH NURSING,PHILADELPHIA,PA 19104. UNIV COLORADO,CHILDRENS HOSP,SCH MED,DEPT PEDIAT,DENVER,CO 80202. NICHHD,OFF SCI POLICY & ANAL,BETHESDA,MD 20892. NICHHD,CTR RES MOTHERS & CHILDREN,BETHESDA,MD 20892. RP GILSTRAP, LC (reprint author), UNIV TEXAS,SW MED CTR,DEPT OBSTET & GYNECOL,DALLAS,TX 75235, USA. NR 0 TC 490 Z9 504 U1 1 U2 7 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 FEB 1 PY 1995 VL 273 IS 5 BP 413 EP 418 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA QD203 UT WOS:A1995QD20300027 ER PT J AU HIBBS, ED AF HIBBS, ED TI CHILD AND ADOLESCENT DISORDERS - ISSUES FOR PSYCHOSOCIAL TREATMENT RESEARCH SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article AB The recent efforts of the National Institute of Mental Health (NIMH) to encourage child and adolescent research are described, including the creation of the Child and Adolescent Psychosocial Interventions Research Consortium as a forum to identify, delineate and examine research needs in psychosocial treatments. This is followed by a summary review of the contents of this special issue: history of psychotherapy research with children, developmental issues, diagnosis and assessment, ecological and cultural validity, laboratory versus clinic research outcomes, cognitive behavioral treatments for childhood disorders, nontraditional treatments, and overview and future directions. Finally, methodological issues that need to be addressed in future research are discussed, such as the developmental level of children in treatment research, issues of comorbidity, family involvement, and duration of treatment. RP HIBBS, ED (reprint author), NIMH,DCTR,CHILD & ADOLESCENT DISORDERS RES BRANCH,ROOM 18C-17,ROCKVILLE,MD 20857, USA. NR 13 TC 11 Z9 11 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0091-0627 J9 J ABNORM CHILD PSYCH JI J. Abnorm. Child Psychol. PD FEB PY 1995 VL 23 IS 1 BP 1 EP 10 DI 10.1007/BF01447041 PG 10 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA QF421 UT WOS:A1995QF42100001 PM 7759668 ER PT J AU ARNOLD, LE AF ARNOLD, LE TI SOME NONTRADITIONAL (UNCONVENTIONAL AND/OR INNOVATIVE) PSYCHOSOCIAL TREATMENTS FOR CHILDREN AND ADOLESCENTS - CRITIQUE AND PROPOSED SCREENING PRINCIPLES SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article ID EYE-MOVEMENT DESENSITIZATION; BIOFEEDBACK; HYPERACTIVITY; STIMULATION; DISORDERS; TACTILE; EEG AB Five examples of nontraditional psychosocial treatments used for children/adolescents are reviewed: eye movement desensitization and reprocessing, electroencephalographic (EEG) biofeedback, deep pressure/touch therapies, stress-challenge treatments, and confrontational scare treatments. The generic recommendations from the September 1992 National Institutes of Health Conference on Unconventional Medical Treatments are summarized. Additional screening principles specific for psychosocial treatments are proposed and applied to the five treatments. The screens do not validate treatment efficacy or evaluate the quality of any previous research, but only facilitate decisions as to whether treatments deserve controlled investigation. Scientific evaluation of the nontraditional treatments reviewed could in general benefit from blinds (at least for assessment); control conditions matched for intensity, frequency, and duration (double blind where feasible); dose-response studies; testing of generalization and endurance supplements or boosters for quick, cheap treatments with time- or domain-limited effects; and comparing cost-effectiveness with established treatments. Two unscientific pitfalls must be avoided: embracing new treatments uncritically and rejecting them without fair examination. These pitfalls must be skirted without dissipating scarce research resources. RP ARNOLD, LE (reprint author), NIMH,CHILD & ADOLESCENT DISORDERS RES BRANCH,PKLAWN 10-104,ROCKVILLE,MD 20857, USA. NR 38 TC 7 Z9 7 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0091-0627 J9 J ABNORM CHILD PSYCH JI J. Abnorm. Child Psychol. PD FEB PY 1995 VL 23 IS 1 BP 125 EP 140 DI 10.1007/BF01447048 PG 16 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA QF421 UT WOS:A1995QF42100008 PM 7759671 ER PT J AU FLEMING, K GREEN, MF AF FLEMING, K GREEN, MF TI BACKWARD-MASKING PERFORMANCE DURING AND AFTER MANIC EPISODES SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article ID SCHIZOPHRENIA SPECTRUM DISORDERS AB In a longitudinal design, 16 inpatients with bipolar mood disorder and 16 normal control participants were administered measures of backward masking. Bipolar inpatients were assessed while actively manic and again following manic episode. Clinical state was determined from ratings on an expanded version of the Brief Psychiatric Rating Scale. Two backward masking paradigms were used: (a) a staircase method, which yielded a critical interstimulus interval, and (b) set interstimulus intervals, which provided a masking function. Bipolar patients performed significantly worse than the normal controls at both sessions, but the Group X Session interaction was nonsignificant with both masking procedures. The masking performance deficit for the manic patients was not related to the presence of psychotic symptoms but seemed to be partially associated with lithium treatment. The results indicate that the impaired masking performance of manic patients is not strictly limited to the period of the manic episode. C1 UNIV CALIF LOS ANGELES, RES CTR, DEPT PSYCHIAT & BIOBEHAV SCI, POB 6022, CAMARILLO, CA 93011 USA. W LOS ANGELES VET AFFAIRS MED CTR, LOS ANGELES, CA USA. ST ELIZABETH HOSP, WASHINGTON, DC 20032 USA. NIMH, BETHESDA, MD 20892 USA. FU NIMH NIH HHS [MH-43292, MH-30911] NR 32 TC 26 Z9 26 U1 0 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD FEB PY 1995 VL 104 IS 1 BP 63 EP 68 PG 6 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA QD428 UT WOS:A1995QD42800007 PM 7897054 ER PT J AU CHEESEMAN, SH HAVLIR, D MCLAUGHLIN, MM GREENOUGH, TC SULLIVAN, JL HALL, D HATTOX, SE SPECTOR, SA STEIN, DS MYERS, M RICHMAN, DD AF CHEESEMAN, SH HAVLIR, D MCLAUGHLIN, MM GREENOUGH, TC SULLIVAN, JL HALL, D HATTOX, SE SPECTOR, SA STEIN, DS MYERS, M RICHMAN, DD TI PHASE I/II EVALUATION OF NEVIRAPINE ALONE AND IN COMBINATION WITH ZIDOVUDINE FOR INFECTION WITH HUMAN-IMMUNODEFICIENCY-VIRUS SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE NEVIRAPINE; NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR; COMBINATION THERAPY; PHASE I/II STUDY; PHARMACOKINETICS ID AIDS-RELATED COMPLEX; HIV-1 REVERSE-TRANSCRIPTASE; PLACEBO-CONTROLLED TRIAL; ANTIGEN LEVELS; DOUBLE-BLIND; TYPE-1; RESISTANCE; INHIBITOR; AZT; PHARMACOKINETICS AB In these Phase I/II open-label clinical trials, 62 persons with human immunodeficiency virus type 1 (HIV-1) infection and CD4(+) cell counts <400/ mm(3) received nevirapine at doses of 12.5, 50, and 200 mg/day, alone or in combination with zidovudine, 200 mg q8h. Nevirapine was well tolerated in the doses tested. Mean steady-state trough levels were 0.23, 1.1, and 1.9 mu g/ml for the 12.5, 50, and 200 mg/day doses, respectively. Early suppression of p24 antigen levels and increase in CD4(+) cell count were reversed following rapid emergence of virus less susceptible to nevirapine. Resistant strains were isolated from all participants by 8 weeks. Nevertheless, reduction of p24 antigen levels to <50% of baseline values persisted for 12 weeks or more in four of seven persons who received 200 mg nevirapine/day in combination with zidovudine: these individuals had been antigenemic on long-term zidovudine therapy, This study demonstrates a direct relationship between drug resistance and effects on surrogate markers in HIV-1 infection. C1 UNIV CALIF SAN DIEGO,MED CTR,SAN DIEGO,CA 92103. NIAID,BETHESDA,MD 20892. BOEHRINGER INGELHEIM PHARMACEUT INC,RIDGEFIELD,CT 06877. RP CHEESEMAN, SH (reprint author), UNIV MASSACHUSETTS,MED CTR,SCH MED,DIV INFECT DIS & IMMUNOL,55 LAKE AVE N,WORCESTER,MA 01655, USA. FU NIAID NIH HHS [AI 27670, AI 25831, AI 29164] NR 39 TC 93 Z9 94 U1 0 U2 4 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 FEB 1 PY 1995 VL 8 IS 2 BP 141 EP 151 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA QD440 UT WOS:A1995QD44000005 PM 7530585 ER PT J AU FIGUEROA, JP BRATHWAITE, AR MORRIS, J WARD, EM PERUGA, A BLATTNER, W VERMUND, SH HAYES, R AF FIGUEROA, JP BRATHWAITE, AR MORRIS, J WARD, EM PERUGA, A BLATTNER, W VERMUND, SH HAYES, R TI RISING HIV-1 PREVALENCE IN STD CLINIC ATTENDERS IN JAMAICA - TRAUMATIC SEX AND GENITAL ULCERS AS RISK-FACTORS - REPLY SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Letter C1 LONDON SCH HYG & TROP MED,LONDON WC1,ENGLAND. PAHO,WASHINGTON,DC. NCI,DIV AIDS,ROCKVILLE,MD. UNIV ALABAMA,BIRMINGHAM,AL. RP FIGUEROA, JP (reprint author), MINIST HLTH,KINGSTON,JAMAICA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD FEB 1 PY 1995 VL 8 IS 2 BP 215 EP 215 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA QD440 UT WOS:A1995QD44000019 ER PT J AU SANTELLI, J KOUZIS, A NEWCOMER, S AF SANTELLI, J KOUZIS, A NEWCOMER, S TI EMERGENCY ROOM AND HOSPITAL DIVERSION FROM SCHOOL CLINICS SO JOURNAL OF ADOLESCENT HEALTH LA English DT Meeting Abstract C1 NICHHD,ROCKVILLE,MD. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD FEB PY 1995 VL 16 IS 2 BP 130 EP 130 PG 1 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA QK156 UT WOS:A1995QK15600007 ER PT J AU FUTTERMAN, D ROGERS, A DANGELO, L LEVIN, L AF FUTTERMAN, D ROGERS, A DANGELO, L LEVIN, L TI TRANSMISSION DYNAMICS AND CLINICAL STATUS OF HIV+ YOUTH SO JOURNAL OF ADOLESCENT HEALTH LA English DT Meeting Abstract C1 NICHHD,BETHESDA,MD. CHILDRENS NATL MED CTR,WASHINGTON,DC. MONTEFIORE MED CTR,BRONX,NY 10467. MT SINAI MED CTR,NEW YORK,NY 10029. NR 0 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD FEB PY 1995 VL 16 IS 2 BP 134 EP 134 PG 1 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA QK156 UT WOS:A1995QK15600016 ER PT J AU ROGERS, A FUTTERMAN, D DANGELO, L LEVIN, L AF ROGERS, A FUTTERMAN, D DANGELO, L LEVIN, L TI FACTORS AFFECTING ANTIRETROVIRAL TREATMENT IN HIV+ YOUTH SO JOURNAL OF ADOLESCENT HEALTH LA English DT Meeting Abstract C1 NICHHD,BETHESDA,MD. CHILDRENS NATL MED CTR,WASHINGTON,DC. MONTEFIORE MED CTR,BRONX,NY 10467. MT SINAI MED CTR,NEW YORK,NY 10029. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD FEB PY 1995 VL 16 IS 2 BP 140 EP 140 PG 1 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA QK156 UT WOS:A1995QK15600027 ER PT J AU DANGELO, LJ ROGERS, A FUTTEMAN, D LEVIN, L AF DANGELO, LJ ROGERS, A FUTTEMAN, D LEVIN, L TI THE GEOGRAPHIC PROFILE OF HIV-INFECTION IN ADOLESCENTS AND YOUNG-ADULTS - RESULTS OF A NATIONWIDE SURVEY SO JOURNAL OF ADOLESCENT HEALTH LA English DT Meeting Abstract C1 CHILDREN NTL MED CTR,WASHINGTON,DC. NICHHD,BETHESDA,MD. MONTEFIORE MED CTR,BRONX,NY 10467. MT SINAI MED CTR,NEW YORK,NY 10029. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD FEB PY 1995 VL 16 IS 2 BP 168 EP 168 PG 1 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA QK156 UT WOS:A1995QK15600083 ER PT J AU MCDERMOTT, M HSU, C MOLLOY, MG MULCAHY, B PHELAN, M SHANAHAN, F OGARA, F ADAMS, C RUBIN, LA CLEGG, DO HUSEBYE, D AMOS, CI WARD, RH KASTNER, DL AF MCDERMOTT, M HSU, C MOLLOY, MG MULCAHY, B PHELAN, M SHANAHAN, F OGARA, F ADAMS, C RUBIN, LA CLEGG, DO HUSEBYE, D AMOS, CI WARD, RH KASTNER, DL TI NON-LINKAGE OF A T-CELL RECEPTOR-GAMMA CHAIN MICROSATELLITE (D7S485) TO RHEUMATOID-ARTHRITIS, IN MULTIPLEX FAMILIES SO JOURNAL OF AUTOIMMUNITY LA English DT Article ID SYNOVIAL-FLUID; DELTA-CELLS; BETA-GENE; LYMPHOCYTES; SCLEROSIS; LOCUS; SUSCEPTIBILITY; POPULATION; BLOOD; MAP AB A highly informative microsatellite marker, D7S485, from the T-cell receptor gamma (TCRG) locus, has been used to study segregation of TCRG genes in 26 multiplex rheumatoid arthritis (RA) families. We used the sib-pair method to assess excess identity-by-descent sharing among affected members in these families and the LINKAGE package of programs was used to calculate two-point lod scores far the D7S485 marker. There was no evidence for segregation of TCRG genes with RA in affected siblings and significantly negative lad scores were obtained from Linkage analyses using bath autosomal dominant and recessive models of inheritance. C1 NATL UNIV IRELAND UNIV COLL CORK,DEPT RHEUMATOL,CORK,IRELAND. NATL UNIV IRELAND UNIV COLL CORK,DEPT MED,CORK,IRELAND. NIAMSD,ARTHRITIS & RHEUMATISM BRANCH,BETHESDA,MD. UNIV TORONTO,DEPT MED,TORONTO,ON,CANADA. UNIV UTAH,DEPT RHEUMATOL,SALT LAKE CITY,UT. UNIV UTAH,DEPT HUMAN GENET,SALT LAKE CITY,UT. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT EPIDEMIOL,HOUSTON,TX. RP MCDERMOTT, M (reprint author), NATL UNIV IRELAND UNIV COLL CORK,DEPT MICROBIOL,CORK,IRELAND. FU NCI NIH HHS [CA49734]; NIAMS NIH HHS [AR40057] NR 29 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD FEB PY 1995 VL 8 IS 1 BP 131 EP 138 DI 10.1006/jaut.1995.0010 PG 8 WC Immunology SC Immunology GA QF809 UT WOS:A1995QF80900010 PM 7734033 ER PT J AU FINN, TM LI, ZM KOCSIS, E AF FINN, TM LI, ZM KOCSIS, E TI IDENTIFICATION OF A BORDETELLA-PERTUSSIS BVG-REGULATED PORIN-LIKE PROTEIN SO JOURNAL OF BACTERIOLOGY LA English DT Note ID VIRULENCE FACTORS; FILAMENTOUS HEMAGGLUTININ; ANTIGENIC MODULATION; SEQUENCES; CLONING; GENE; VIR; NUCLEOTIDE; MUTATIONS AB Bordetella pertussis 18323 produces a bvg-regulated 39.1-kDa porin-like protein, OmpQ. OmpQ had 61% similarity to the major porin of B. pertussis and contains conserved regions common to both the neisserial and enteric porin families. The results of Southern blot analysis indicate that strains of Bordetella parapertussis and Bordetella bronchiseptica but not Bordetella avium contain this gene. C1 US FDA,CTR BIOL EVALUAT & RES,PERTUSSIS LAB,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,MYCOBACTERIAL DIS & CELLULAR IMMUNOL LAB,BETHESDA,MD 20892. NIAMS,STRUCT BIOL LAB,BETHESDA,MD 20892. NR 26 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD FEB PY 1995 VL 177 IS 3 BP 805 EP 809 PG 5 WC Microbiology SC Microbiology GA QD435 UT WOS:A1995QD43500043 PM 7836316 ER PT J AU EVANS, GL NI, BF HRYCYNA, CA CHEN, D AMBUDKAR, SV PASTAN, I GERMANN, UA GOTTESMAN, MM AF EVANS, GL NI, BF HRYCYNA, CA CHEN, D AMBUDKAR, SV PASTAN, I GERMANN, UA GOTTESMAN, MM TI HETEROLOGOUS EXPRESSION SYSTEMS FOR P-GLYCOPROTEIN - ESCHERICHIA-COLI, YEAST, AND BACULOVIRUS SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Review DE P-GLYCOPROTEIN; MULTIDRUG RESISTANCE; MDR; ATPASE; DRUG TRANSPORT; ATP-BINDING CASSETTE (ABC) TRANSPORTERS ID PREDICTED TRANSMEMBRANE DOMAIN; BACTERIAL TRANSPORT PROTEINS; RESISTANT HUMAN-CELLS; MULTIDRUG-RESISTANCE; FUNCTIONAL EXPRESSION; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; RECOMBINANT BACULOVIRUS; INSECT CELLS; MOUSE MDR1 AB Chemotherapy, though it remains one of the front-line weapons used to treat human cancer, is often ineffective due to drug resistance mechanisms manifest in tumor cells. One common pattern of drug resistance, characterized by simultaneous resistance to multiple amphipathic, but otherwise structurally dissimilar anticancer drugs, is termed multidrug resistance. Multidrug resistance in various model systems, covering the phylogenetic range from bacteria to man, can be conferred by mammalian P-glycoproteins (PGPs), often termed multidrug transporters. PGPs are 170-kD polytopic membrane proteins, predicted to consist of two homologous halves, each with six membrane spanning regions and one ATP binding site. They are members of the ATP-binding cassette (ABC) superfamily of transporters, and are known to function biochemically as energy-dependent drug efflux pumps. However, much remains to be learned about PGP structure-function relationships, membrane topology, posttranslational regulation, and bioenergetics of drug transport. Much of the recent progress in the study of the human and mouse PGPs has come from heterologous expression systems which offer the benefits of ease of genetic selection and manipulation, and/or short generation times of the organism in which PGPs are expressed, and/or high-level expression of recombinant PGP. Here we review recent studies of PGP in E. coli, baculovirus, and yeast systems and evaluate their utility for the study of PGPs, as well as other higher eukaryotic membrane proteins. C1 NCI, CELL BIOL LAB, BETHESDA, MD 20892 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT MED, DIV NEPHROL, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT PHYSIOL, BALTIMORE, MD 21205 USA. RP EVANS, GL (reprint author), NCI, MOLEC BIOL LAB, 37 CONVENT DR MSC 4255, BETHESDA, MD 20892 USA. RI Ambudkar, Suresh/B-5964-2008 NR 66 TC 39 Z9 39 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0145-479X EI 1573-6881 J9 J BIOENERG BIOMEMBR JI J. Bioenerg. Biomembr. PD FEB PY 1995 VL 27 IS 1 BP 43 EP 52 DI 10.1007/BF02110330 PG 10 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA QT916 UT WOS:A1995QT91600007 PM 7629051 ER PT J AU GERMANN, UA CHAMBERS, TC AMBUDKAR, SV PASTAN, I GOTTESMAN, MM AF GERMANN, UA CHAMBERS, TC AMBUDKAR, SV PASTAN, I GOTTESMAN, MM TI EFFECTS OF PHOSPHORYLATION OF P-GLYCOPROTEIN ON MULTIDRUG-RESISTANCE SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Review DE MULTIDRUG RESISTANCE; P-GLYCOPROTEIN; MULTIDRUG TRANSPORTER; PROTEIN KINASE C; CAMP-DEPENDENT PROTEIN KINASE; PHOSPHORYLATION SITES; LINKER REGION ID PROTEIN-KINASE-C; HAMSTER OVARY CELLS; MDR GENE FAMILY; PLASMA-MEMBRANE GLYCOPROTEIN; BACTERIAL TRANSPORT PROTEINS; MUTANT REGULATORY SUBUNIT; BREAST-CARCINOMA CELLS; CFTR CHLORIDE CHANNEL; HL-60 LEUKEMIA-CELLS; HUMAN-KB CELLS AB Cells expressing elevated levels of the membrane phosphoprotein P-glycoprotein exhibit a multidrug resistance phenotype. Studies involving protein kinase activators and inhibitors have implied that covalent modification of P-glycoprotein by phosphorylation may modulate its biological activity as a multidrug transporter. Most of these reagents, however, have additional mechanisms of action and may alter drug accumulation within multidrug resistant cells independent of, or in addition to, their effects on the state of phosphorylation of P-glycoprotein. The protein kinase(s) responsible for P-glycoprotein phosphorylation has(ve) not been unambiguously identified, although several possible candidates have been suggested. Recent biochemical analyses demonstrate that the major sites of phosphorylation are clustered within the linker region that connects the two homologous halves of P-glycoprotein. Mutational analyses have been initiated to confirm this finding. Preliminary data obtained from phosphorylation- and dephosphorylation-defective mutants suggest that phosphorylation of P-glycoprotein is not essential to confer multidrug resistance. C1 UNIV ARKANSAS MED SCI HOSP, DEPT BIOCHEM & MOLEC BIOL, LITTLE ROCK, AR 72205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT MED, DIV NEPHROL, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT PHYSIOL, BALTIMORE, MD 21205 USA. NCI, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. NCI, CELL BIOL LAB, BETHESDA, MD 20892 USA. RP GERMANN, UA (reprint author), VERTEX PHARMACEUT INC, 40 ALLSTON ST, CAMBRIDGE, MA 02139 USA. RI Ambudkar, Suresh/B-5964-2008 NR 96 TC 74 Z9 74 U1 1 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0145-479X EI 1573-6881 J9 J BIOENERG BIOMEMBR JI J. Bioenerg. Biomembr. PD FEB PY 1995 VL 27 IS 1 BP 53 EP 61 DI 10.1007/BF02110331 PG 9 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA QT916 UT WOS:A1995QT91600008 PM 7629052 ER PT J AU MASI, L BRANDI, ML ROBEY, PG CRESCIOLI, C CALVO, JC BERNABEI, P KERR, JM YANAGISHITA, M AF MASI, L BRANDI, ML ROBEY, PG CRESCIOLI, C CALVO, JC BERNABEI, P KERR, JM YANAGISHITA, M TI BIOSYNTHESIS OF BONE SIALOPROTEIN BY A HUMAN OSTEOCLAST-LIKE CELL-LINE (FLG-29.1) SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID MINERALIZED-TISSUE FORMATION; SECRETED PHOSPHOPROTEIN-1; BSP; LOCALIZATION; EXPRESSION; PROTEINS; MATRIX; OSTEOPONTIN; SULFATE; DIFFERENTIATION AB Biosynthesis of bone sialoprotein (BSP) by a human osteoclastic cell line (FLG 29.1) during its differentiation induced by phorbol 12-myristate 13-acetate (TPA) was studied using metabolic radiolabeling experiments. The FLG 29.1. cells were metabolically radiolabeled with [H-3]glucosamine and [S-35]sulfate, and the labeled glycoproteins were analyzed by anion exchange chromatography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoprecipitation experiments. One of the major glycoproteins synthesized by the TPA-treated FLG 29.1 cells was sulfated, had an identical electrophoretic mobility to purified BSP, and could be immunoprecipitated with a specific antibody against human BSP (LF 6). Thus, this glycoprotein was tentatively identified as the BSP. Furthermore, mRNA for BSP was also detected in TPA-treated FLG 29.1 cells by RNA-polymerase chain reaction. Most BSP synthesized by FLG 29.1 cells remained cell-associated, and this is in contrast with those synthesized by osteoblasts, where the protein is rapidly released into the extracellular matrix. Immunocytochemistry using an anti-BSP antibody showed a prominent paranuclear (suggestive of Golgi apparatus) localization of BSP in the TPA-treated FLG 29.1 cells after permeabilization, while untreated cells were not significantly immunostained. Localization of BSP at the plasma membrane was also demonstrated in the TPA-treated FLG 29.1 cells by the fluorescence-activated cell sorting analysis. Since TPA has been demonstrated to induce expression of various osteoclastic characteristics in FLG 29.1 cells, induction of BSP expression by TPA suggests that the protein may play a role during the differentiation process of osteoclasts or in functions of differentiated osteoclasts. C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. UNIV FLORENCE,DIPARTIMENTO FISIOPATOL CLIN,SEZ ENDOCRINOL,FLORENCE,ITALY. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 34 TC 18 Z9 18 U1 0 U2 2 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD FEB PY 1995 VL 10 IS 2 BP 187 EP 196 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QF460 UT WOS:A1995QF46000003 PM 7754798 ER PT J AU LIPPINCOTTSCHWARTZ, J COLE, NB MAROTTA, A CONRAD, PA BLOOM, GS AF LIPPINCOTTSCHWARTZ, J COLE, NB MAROTTA, A CONRAD, PA BLOOM, GS TI KINESIN IS THE MOTOR FOR MICROTUBULE-MEDIATED GOLGI-TO-ER MEMBRANE TRAFFIC SO JOURNAL OF CELL BIOLOGY LA English DT Article ID BOVINE BRAIN KINESIN; ADP-RIBOSYLATION FACTOR; FAST AXONAL-TRANSPORT; ENDOPLASMIC-RETICULUM; CYTOPLASMIC DYNEIN; LIGHT-CHAINS; CULTURED-CELLS; HEAVY-CHAIN; BETA-COP; SUBCELLULAR-LOCALIZATION AB The distribution and dynamics of both the ER and Golgi complex in animal cells are known to be dependent on microtubules; in many cell types the ER extends toward the plus ends of microtubules at the cell periphery and the Golgi clusters at the minus ends of microtubules near the centrosome. In this study we provide evidence that the microtubule motor, kinesin, is present on membranes cycling between the ER and Golgi and powers peripherally directed movements of membrane within this system. Immunolocalization of kinesin at both the light and electron microscopy levels in NRK cells using the H1 monoclonal antibody to kinesin heavy chain, revealed kinesin to be associated with all membranes of the ER/Golgi system. At steady-state at 37 degrees C, however, kinesin was most concentrated on peripherally distributed, pre-Golgi structures containing beta COP and vesicular stomatitis virus glycoprotein newly released from the ER. Upon temperature reduction or nocodazole treatment, kinesin's distribution shifted onto the Golgi, while with brefeldin A (BFA)-treatment, kinesin could be found in both Golgi-derived tubules and in the ER. This suggested that kinesin associates with membranes that constitutively cycle between the ER and Golgi. Kinesin's role on these membranes was examined by microinjecting kinesin antibody. Golgi-to-ER but not ER-to-Golgi membrane transport was found to be inhibited by the microinjected anti-kinesin, suggesting kinesin powers the microtubule plus end-directed recycling of membrane to the ER, and remains inactive on pre-Golgi intermediates that move toward the Golgi complex. C1 UNIV TEXAS,SW MED CTR,DEPT CELL BIOL & NEUROSCI,DALLAS,TX 75235. RP LIPPINCOTTSCHWARTZ, J (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BLDG 18T,RM 101,BETHESDA,MD 20892, USA. FU NINDS NIH HHS [NS30485, NS23868] NR 80 TC 201 Z9 203 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD FEB PY 1995 VL 128 IS 3 BP 293 EP 306 DI 10.1083/jcb.128.3.293 PG 14 WC Cell Biology SC Cell Biology GA QD398 UT WOS:A1995QD39800005 PM 7844144 ER PT J AU MURRAY, GJ OLIVER, KL JIN, FS BRADY, RO AF MURRAY, GJ OLIVER, KL JIN, FS BRADY, RO TI STUDIES ON THE TURNOVER OF EXOGENOUS MANNOSE-TERMINAL GLUCOCEREBROSIDASE IN RAT-LIVER LYSOSOMES SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE ENZYMES; REPLACEMENT THERAPY; GAUCHERS DISEASE; LYSOSOMES ID ENZYME-REPLACEMENT THERAPY; GAUCHERS-DISEASE; CELLS; PURIFICATION; GLYCOPROTEIN; PROTEINS AB Mannose-terminal glucocerebrosidase prepared by exoglycosidase digestion of human placental glucocerebrosidase is reported effective in the treatment of patients with type 1 Gaucher's disease [Barton et al. (1991); N Engl J Med 324:1464-1470]. However, the amount of enzyme that is necessary for therapeutic effect is much higher than would be predicted from in vitro activity measurements. We have investigated the fate of infused enzyme following intravenous administration in Sprague-Dawley rats. In this model system, the enzyme is rapidly cleared from the plasma compartment by receptor-mediated endocytosis via the mannose-specific receptor present on reticuloendothelial cells. Enzyme activity measured in rat liver biopsy specimens at various times post-infusion revealed a rapid initial loss of approximately one-half of the maximum delivered enzyme in the first hour followed by a slower decay with a half-life of approximately 6-8 h. The loss in enzyme activity is paralleled by a loss in enzyme protein when analyzed by Western blots. There is no evidence for return of enzyme activity or inactive enzyme protein to the plasma. Incomplete integration into the lysosomal membrane was demonstrated by the use of differential extraction of purified rat liver lysosomes to distinguish between lumenal and membrane bound enzyme. Immunoelectron microscopy of rat liver following infusion of mannose-terminal glucocerebrosidase confirmed localization of the delivered enzyme primarily within the lumen of the lysosomes of Kupffer cells and to a lesser extent associated with the lysosomal membrane. Enzyme activity was stable in isolated rat liver lysosomes preloaded with mannose-terminal glucocerebrosidase and incubated in the absence or presence of ATP. Acidification of the lysosomes to pH 3 results in a rapid loss of enzyme activity and protein; however, the relationship between the in vitro loss and the loss in enzyme activity in intact liver is not clear. We conclude from these studies that rapid intracellular degradation of administered glucocerebrosidase is the prime factor responsible for the high dose required for effective treatment of Caucher's disease. (C) 1995 Wiley-Liss, Inc. RP MURRAY, GJ (reprint author), NIH,NINDS,DEV & METAB NEUROL BRANCH,BLDG 10,ROOM 3D-04,BETHESDA,MD 20892, USA. NR 27 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD FEB PY 1995 VL 57 IS 2 BP 208 EP 217 DI 10.1002/jcb.240570205 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QE354 UT WOS:A1995QE35400004 PM 7759558 ER PT J AU FORMIGLI, L ORLANDINI, SZ BENVENUTI, S MASI, L PINTO, A GATTEI, V BERNABEI, PA ROBEY, PG COLLINOSDOBY, P BRANDI, ML AF FORMIGLI, L ORLANDINI, SZ BENVENUTI, S MASI, L PINTO, A GATTEI, V BERNABEI, PA ROBEY, PG COLLINOSDOBY, P BRANDI, ML TI IN-VITRO STRUCTURAL AND FUNCTIONAL-RELATIONSHIPS BETWEEN PREOSTEOCLASTIC AND BONE ENDOTHELIAL-CELLS - A JUXTACRINE MODEL FOR MIGRATION AND ADHESION OF OSTEOCLAST PRECURSORS SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID ARG-GLY-ASP; VITRONECTIN RECEPTOR; MONONUCLEAR PHAGOCYTES; FIBRONECTIN RECEPTOR; VASCULAR INVASION; GLYCOPROTEIN-IIB; DIFFERENTIATION; GROWTH; RESORPTION; INTEGRINS AB The role of vascularization in the process of bone resorption has not been clarified. The interactions between vascular endothelium and osteoclast progenitors were analyzed using clonal cell lines of bone-derived endothelial and preosteoclastic cells. Insulin-like growth factor I is a major chemotactic stimulator of preosteoclastic cell migration mediated by bone endothelial cells. Osteoclast precursors rapidly adhered to bone endothelial monolayers. This phenomenon appeared to be cell-specific and mediated through the binding of vitronectin and fibronectin receptors to fibronectin. In addition, direct contact with bone endothelial cells induced osteoclast progenitors to differentiate into more mature elements, with the tendency to cluster together to form large multinucleated cells. These findings demonstrated specific in vitro interactions between bone endothelial cells and osteoclast progenitors, offering a new model for understanding the molecular mechanisms which direct the processes of osteoclast recruitment and ontogeny. (C) 1995 Wiley-Liss, Inc. C1 UNIV FLORENCE,SCH MED,DEPT CLIN PHYSIOPATHOL,ENDOCRINE UNIT,I-50139 FLORENCE,ITALY. UNIV FLORENCE,DEPT ANAT,I-50139 FLORENCE,ITALY. UO HEMATOL,I-50139 FLORENCE,ITALY. CTR RIFERIMENTO ONCOL,LEUKEMIA UNIT,I-3308 AVIANO,ITALY. NIDR,BONE RES BRANCH,BETHESDA,MD 20892. WASHINGTON UNIV,DEPT BIOL,ST LOUIS,MO 63130. WASHINGTON UNIV,DIV BONE & MINERAL METAB,ST LOUIS,MO 63130. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 83 TC 26 Z9 26 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD FEB PY 1995 VL 162 IS 2 BP 199 EP 212 DI 10.1002/jcp.1041620206 PG 14 WC Cell Biology; Physiology SC Cell Biology; Physiology GA QH423 UT WOS:A1995QH42300005 PM 7529767 ER PT J AU GROSSMANN, A RABINOVITCH, PS LANE, MA JINNEMAN, JC INGRAM, DK WOLF, NS CUTLER, RG ROTH, GS AF GROSSMANN, A RABINOVITCH, PS LANE, MA JINNEMAN, JC INGRAM, DK WOLF, NS CUTLER, RG ROTH, GS TI INFLUENCE OF AGE, SEX, AND DIETARY RESTRICTION ON INTRACELLULAR FREE CALCIUM RESPONSES OF CD4(+) LYMPHOCYTES IN RHESUS-MONKEYS (MACACA-MULATTA) SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID T-CELL SUBSETS; FLOW-CYTOMETRY; OLD MICE; SIGNAL TRANSDUCTION; PROLIFERATION; HUMANS; YOUNG; HETEROGENEITY; GENERATION; IMMUNITY AB The influence of aging and dietary restriction on increase in intracellular free calcium ([Ca2+](i)) Of CD4(+) lymphocytes from Macaca mulatta was examined after stimulation with anti-CD3 mAb. We used a flow cytometric assay with the dye indo-1 and either direct or reciprocal immunofluorescent staining to identify CD4(+) cells. After stimulation with anti-CD3 mAb, intracellular free calcium responses were reduced in CD4(+) lymphocytes from old male and female ad libitum fed monkeys compared to young and adult male or female monkeys. Old female monkeys had significantly lower [Ca2+](i) than did old male monkeys. The reduced responses were in part related to a decreased percentage of responding cells. Dietary restrition of males over a four-year period did not alter [Ca2+](i) response compared to ad libitum fed male monkeys. Female monkeys of all ages (which were restricted only for four months) also had similar [Ca2+](i) responses to ad libitum fed controls. Our data suggest that age-related changes in [Ca2+](i) responses are similar between humans and M. mulatta, and that over these intervals, no effects of caloric restrictions can be detected. (C) 1995 Wiley-Liss, Inc. C1 UNIV WASHINGTON, DEPT PATHOL, SEATTLE, WA 98195 USA. NIA, FRANCIS SCOTT KEY MED CTR, GERONTOL RES CTR, MOLEC PHYSIOL & GENET SECT, BALTIMORE, MD 21224 USA. NIA, FRANCIS SCOTT KEY MED CTR, GERONTOL RES CTR, NATHAN SHOCK LABS, BALTIMORE, MD 21224 USA. RP UNIV WASHINGTON, DEPT COMPARAT MED, SB-42, SEATTLE, WA 98195 USA. FU NIA NIH HHS [AG01751, AG07724] NR 28 TC 11 Z9 12 U1 0 U2 0 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9541 EI 1097-4652 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD FEB PY 1995 VL 162 IS 2 BP 298 EP 303 DI 10.1002/jcp.1041620216 PG 6 WC Cell Biology; Physiology SC Cell Biology; Physiology GA QH423 UT WOS:A1995QH42300015 PM 7822437 ER PT J AU LAW, WA MAPOU, RL ROLLER, TL MARTIN, A NANNIS, ED TEMOSHOK, LR AF LAW, WA MAPOU, RL ROLLER, TL MARTIN, A NANNIS, ED TEMOSHOK, LR TI REACTION-TIME SLOWING IN HIV-1-INFECTED INDIVIDUALS - ROLE OF THE PREPARATORY INTERVAL SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS DEMENTIA COMPLEX; ASYMPTOMATIC HIV-INFECTION; PARKINSONS-DISEASE; NEUROPSYCHOLOGICAL PERFORMANCE; HOMOSEXUAL MEN; BASAL GANGLIA; IMMUNE FUNCTION; DEPRESSION; COGNITION AB Psychomotor speed and directed attention were evaluated in 83 human immunodeficiency virus-1-infected individuals (HIV+) and 50 HIV-1 seronegative (HIV-) control participants using simple and choice reaction time (RT) tasks. The simple RT task included 1- and 3-s, irregularly varied preparatory intervals (PI) between the warning and target lights. Relative to the HIV- group, simple and choice RT were significantly slowed in the HIV+ group. Further, again relative to the HIV- controls, the HIV+ group did not show expected faster RT with increased response preparation time in the simple RT task. This also occurred in some HIV+ subjects who did not have psychomotor slowing. These findings suggest that RT performance in HIV-1-infected individuals may reflect separate processes associated with psychomotor slowing and impaired ability to direct attention. Possible neural mechanisms associated with control of these processes are discussed. C1 HENRY M JACKSON FDN ADVANCEMENT MIL MED,ROCKVILLE,MD. MIL MED CONSORTIUM APPL RETROVIRAL RES,ROCKVILLE,MD. UNIFORMED SERV UNIV HLTH SCI,DEPT PSYCHIAT,BETHESDA,MD 20814. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. RI martin, alex/B-6176-2009 NR 63 TC 20 Z9 20 U1 0 U2 1 PU SWETS ZEITLINGER BV PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD FEB PY 1995 VL 17 IS 1 BP 122 EP 133 DI 10.1080/13803399508406587 PG 12 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA QJ150 UT WOS:A1995QJ15000013 PM 7608294 ER PT J AU PETRAGLIA, F DEVITA, D GALLINELLI, A AGUZZOLI, L GENAZZANI, AR ROMERO, R WOODRUFF, TK AF PETRAGLIA, F DEVITA, D GALLINELLI, A AGUZZOLI, L GENAZZANI, AR ROMERO, R WOODRUFF, TK TI ABNORMAL CONCENTRATION OF MATERNAL SERUM ACTIVIN-A IN GESTATIONAL DISEASES SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; HUMAN CHORIONIC-GONADOTROPIN; HUMAN PLACENTAL CELLS; PRETERM LABOR; INHIBIN SUBUNITS; LOCALIZATION; SECRETION; PROGESTERONE; STIMULATION; PREGNANCY AB Serum plasma activin-A is measurable in the maternal circulation of healthy pregnant women, increases in specimens collected during the third trimester of gestation, and is highest at parturition. Hormone abnormalities are known to be associated with preterm labor or diabetes in pregnancy. Therefore, in the present study serum activin-A levels in normal controls were compared to those in pregnant women with preterm labor or gestational diabetes. In some cases, values were obtained before and after insulin therapy. In other controls and patients with preterm labor, the activin-A concentration in cord serum was also studied. A newly developed two-site immunotest was used to determine activin-A levels. Subjects included normal controls (n = 7), who were sampled throughout gestation every 5 weeks; pregnant women at term (38-40 weeks) not in labor (n = 22); pregnant women at term in spontaneous labor (<3.0 cm dilated; n = 42); women in preterm labor (25-35 weeks; n = 38); and women with gestational diabetes (20-39 weeks; n = 9). In control women, serum activin-A levels increased from 4.8 +/- 5.5 mu g/L (mean +/- SD) at 20 weeks to 25.4 +/- 27.8 mu g/L at 40 weeks (P < 0.01), and values correlated with gestational age. Pregnant women in preterm labor had serum activin-A concentrations (89.04 +/- 173.31 mu g/L) higher than those in normal controls (P < 0.01), and no significant correlation to gestational age was found in this group of pregnant women. Healthy women in labor showed serum activin-A concentrations higher than those in women at term but not in labor (P < 0.01). Diabetic patients had serum activin-A concentrations (52.39 +/- 23.32 mu g/L) significantly higher than those in normal controls. In these patients, maternal serum activin-A concentrations significantly decreased to the range in healthy controls at the same gestational age after insulin therapy (9.48 +/- 3.82 mu g/L). The present study shows that preterm labor is associated with increased concentrations of activin-A in the maternal circulation and cord serum. Hypersecretion of activin-A is also shown in same patients with gestation diabetes; this reverts to normal after insulin treatment. C1 UNIV PISA, DEPT OBSTET & GYNECOL, PISA, ITALY. NICHHD, PERINATOL RES BRANCH, BETHESDA, MD 20892 USA. GENENTECH INC, S SAN FRANCISCO, CA 94080 USA. RP PETRAGLIA, F (reprint author), UNIV MODENA, DEPT OBSTET & GYNECOL, VIA POZZO 71, I-41100 MODENA, ITALY. RI PETRAGLIA, Felice/K-6535-2016 OI PETRAGLIA, Felice/0000-0002-8851-625X NR 26 TC 88 Z9 90 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB PY 1995 VL 80 IS 2 BP 558 EP 561 DI 10.1210/jc.80.2.558 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QG498 UT WOS:A1995QG49800042 PM 7852520 ER PT J AU COHEN, LE WONDISFORD, FE SALVATONI, A MAGHNIE, M BRUCKERDAVIS, F WEINTRAUB, BD RADOVICK, S AF COHEN, LE WONDISFORD, FE SALVATONI, A MAGHNIE, M BRUCKERDAVIS, F WEINTRAUB, BD RADOVICK, S TI A HOT-SPOT IN THE PIT-1 GENE RESPONSIBLE FOR COMBINED PITUITARY-HORMONE DEFICIENCY - CLINICAL AND MOLECULAR CORRELATES SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID THYROTROPIN-RELEASING-HORMONE; TRANSCRIPTION FACTOR PIT-1/GHF-1; POU-SPECIFIC DOMAIN; BETA-SUBUNIT GENE; GROWTH-HORMONE; PROLACTIN GENE; TSH RESPONSE; EXPRESSION; MUTATION; CHILDREN AB Pit-1 is a member of the POU family of transcription factors regulating mammalian development. Pit-1 is thought to be the major cell-specific activator of both the somatotrophs and lactotrophs in the anterior pituitary. When bound to DNA, Pit-1 activates GH and PRL gene expression. Pit-1 is also important for hormonal regulation of the PRL and TSH-beta genes by TRH and cAMP. We studied two unrelated patients with GH, PRL, and TSH deficiencies. Both patients have the same point mutation in the POU homeodomain of the Pit-1 gene (R271W). Patient 1 was studied as an adult and had combined deficiencies of GH, PRL, and TSH. Patient 2, who was studied in infancy, also had GH and PRL deficiencies, but had low thyroid hormone levels with a measurable basal level of TSH and a delayed response of TSH to TRH. Consequently, the current description of Pit-1 gene mutations leading to complete GH, PRL, and TSH deficiencies needs to be expanded to GH and PRL deficiencies associated with a compromise of the thyrotroph's ability to synthesize TSH. C1 BETH ISRAEL HOSP, DEPT MED, BOSTON, MA 02215 USA. UNIV PAVIA, POLICLIN SAN MATTEO, IRCCS, DEPT PEDIAT, I-27100 PAVIA, ITALY. NIDDKD, MOLEC & CELLULAR ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. RP COHEN, LE (reprint author), CHILDRENS HOSP, DIV ENDOCRINOL, 300 LONGWOOD AVE, BOSTON, MA 02115 USA. OI Salvatoni, Alessandro/0000-0002-9604-810X FU NIDDK NIH HHS [1-F32-DK-08965] NR 37 TC 93 Z9 95 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD FEB PY 1995 VL 80 IS 2 BP 679 EP 684 DI 10.1210/jc.80.2.679 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QG498 UT WOS:A1995QG49800062 PM 7852536 ER PT J AU MCCAFFREY, TA POMERANTZ, KB SANBORN, TA SPOKOJNY, AM DU, BH PARK, MH FOLK, JE LAMBERG, A KIVIRIKKO, KI FALCONE, DJ MEHTA, SB HANAUSKEABEL, HM AF MCCAFFREY, TA POMERANTZ, KB SANBORN, TA SPOKOJNY, AM DU, BH PARK, MH FOLK, JE LAMBERG, A KIVIRIKKO, KI FALCONE, DJ MEHTA, SB HANAUSKEABEL, HM TI SPECIFIC-INHIBITION OF EIF-5A AND COLLAGEN HYDROXYLATION BY A SINGLE-AGENT - ANTIPROLIFERATIVE AND FIBROSUPPRESSIVE EFFECTS ON SMOOTH-MUSCLE CELLS FROM HUMAN CORONARY-ARTERIES SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE VASCULAR SMOOTH MUSCLE; CELL DIVISION; COLLAGEN; HYDROXYLASES; MIMOSINE ID TRANSFORMING GROWTH FACTOR-BETA-1; PROLYL 4-HYDROXYLASE; EXTRACELLULAR-MATRIX; I PROCOLLAGEN; BINDING; PROTEIN; 2-OXOGLUTARATE; INJURY; SITE; GROWTH-FACTOR-BETA-1 AB Restenosis occurs in 35% of patients within months after balloon angioplasty, due to a fibroproliferative response to vascular injury. These studies describe a combined fibrosuppressive/antiproliferative strategy on smooth muscle cells cultured from human primary atherosclerotic and restenotic coronary arteries and from normal rat aortas. L-Mimosine suppressed the posttranslational hydroxylation of the precursors for collagen and for eukaryotic initiation factor-5A (eIF-5A) by directly inhibiting the specific protein hydroxylases involved,prolyl 4-hydroxylase (E.C. 1.14.11.2) and deoxyhypusyl hydroxylase (E.C. 1.14.99.29), respectively. Inhibition of deoxyhypusyl hydroxylation correlated with a dose-dependent inhibition of DNA synthesis. Inhibition of prolyl hydroxylation caused a dose-dependent reduction in the secretion of hydroxyproline-containing protein and decreased the formation of procollagen types I and III. The antifibroproliferative action could not be attributed to nonspecific or toxic effects of mimosine, appeared to be selective for the hydroxylation step in the biosynthesis of the procollagens and of eIF-5A, and was reversible upon removal of the compound. The strategy of targeting these two protein hydroxylases has important implications for the pathophysiology of restenosis and for the development of agents to control fibroproliferative diseases. C1 CORNELL UNIV,NEW YORK HOSP,COLL MED,DEPT MED,DIV HEMATOL ONCOL,NEW YORK,NY 10021. CORNELL UNIV,NEW YORK HOSP,COLL MED,DEPT PATHOL CELL BIOL & ANAT,NEW YORK,NY 10021. CORNELL UNIV,NEW YORK HOSP,COLL MED,CARDIAC CATHETERIZAT LAB,NEW YORK,NY 10021. CORNELL UNIV,NEW YORK HOSP,COLL MED,DEPT PEDIAT,NEW YORK,NY 10021. NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. UNIV OULU,DEPT MED BIOCHEM,OULU,FINLAND. FU NHLBI NIH HHS [HL-42606, HL-46403, HL-18828] NR 55 TC 49 Z9 49 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 1995 VL 95 IS 2 BP 446 EP 455 DI 10.1172/JCI117684 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA QG209 UT WOS:A1995QG20900004 PM 7860726 ER PT J AU SHETTY, HU SCHAPIRO, MB HOLLOWAY, HW RAPOPORT, SI AF SHETTY, HU SCHAPIRO, MB HOLLOWAY, HW RAPOPORT, SI TI POLYOL PROFILES IN DOWN-SYNDROME MYOINOSITOL, SPECIFICALLY, IS ELEVATED IN THE CEREBROSPINAL-FLUID SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE CARBOHYDRATES; PHOSPHATIDYLINOSITOLS; BRAIN; TRISOMY; ALZHEIMER DISEASE ID CEREBRAL GLUCOSE-UTILIZATION; DOWNS-SYNDROME; MYOINOSITOL TRANSPORT; BRAIN; METABOLISM; LITHIUM; ADULTS AB Polyols are reduction products of aldoses and ketoses; their concentrations in tissues can reflect carbohydrate metabolism. Several polyol species were quantitated in cerebrospinal fluid (CSF) and plasma from 10 Down Syndrome (trisomy 21) subjects between the ages of 22 and 63 years (3 of whom were demented) and from 10 healthy age-matched controls, using a gas chromatographic/mass spectrometric technique. The mean CSF concentration and the mean CSF/plasma concentration ratio of myo-inositol were significantly elevated in Down syndrome compared with controls, but were not correlated with the presence of dementia in the Down subjects. Plasma myo-inositol was not significantly altered in these subjects. No significant difference between Down syndrome and controls was found for CSF concentrations of mannitol, sorbitol, galactitol, ribitol, arabitol, or 1,5-anhydrosorbitol, but plasma mannitol, ribitol and arabitol were elevated in Down syndrome. The present observation provides new impetus for studying synthesis and transport of myo-inositol as well as phosphatidylinositol cycle in trisomy 21 disorder. RP SHETTY, HU (reprint author), NIA,NEUROSCI LAB,BLDG 10,ROOM 6C 103,BETHESDA,MD 20892, USA. NR 34 TC 48 Z9 48 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 1995 VL 95 IS 2 BP 542 EP 546 DI 10.1172/JCI117696 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA QG209 UT WOS:A1995QG20900016 PM 7860736 ER PT J AU PUCK, JM PEPPER, AE BEDARD, PM LAFRAMBOISE, R AF PUCK, JM PEPPER, AE BEDARD, PM LAFRAMBOISE, R TI FEMALE GERM-LINE MOSAICISM AS THE ORIGIN OF A UNIQUE IL-2 RECEPTOR GAMMA-CHAIN MUTATION CAUSING X-LINKED SEVERE COMBINED IMMUNODEFICIENCY SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Note DE CYTOKINE RECEPTOR; WSXWS MOTIF; GENETIC LINKAGE; HAPLOTYPE; SINGLE STRAND CONFORMATION POLYMORPHISM ID CHROMOSOME INACTIVATION; FUNCTIONAL COMPONENT; LINKAGE; SCIDX1; HEMOPHILIA; PATTERNS; MARKERS; LOCUS; MAPS; DNA AB The IL2RG gene encoding the gamma chain of the lymphocyte receptor for IL-2 lies in human Xq13.1 and is mutated in males with X-linked severe combined immunodeficiency (SCID). In a large Canadian pedigree genetic linkage studies demonstrated that the proband's grandmother was the source of an X-linked SCID mutation. However, her T cells did not show the expected skewed X chromosome inactivation pattern of female carriers of SCID, despite her having one affected son and two carrier daughters' with skewed ii inactivation. Single strand conformation polymorphism analysis of IL2RG in the affected proband was abnormal in exon 5; sequencing revealed a nine nucleotide in-frame duplication insertion. The three duplicated amino acids included the first tryptophan of the ''WSXWS'' motif found in all members of the;cytokine receptor gene superfamily. Mutation detection in the pedigree confirmed that the founder grandmother's somatic cells had only normal IL2RG, and further showed that the SCID-associated X chromosome haplotype was inherited by three daughters, one with a wild type IL2RG gene and two others with the insertional mutation. Female germ line mosaicism is unusual, but its presence in this X-linked SCID family emphasizes the limitations of genetic diagnosis by linkage as compared with direct mutation analysis. C1 CHU LAVAL,DEPT IMMUNOL,ST FOY,PQ G1V 4G2,CANADA. CHU LAVAL,DEPT GENET,ST FOY,PQ G1V 4G2,CANADA. CHU LAVAL,DEPT PEDIAT,ST FOY,PQ G1V 4G2,CANADA. RP PUCK, JM (reprint author), NIH,NATL CTR HUMAN GENOME RES,HUMAN GENE TRANSFER LAB,IMMUNOL GENET SECT,BLDG 49,RM3W14,BETHESDA,MD 20892, USA. NR 29 TC 34 Z9 36 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD FEB PY 1995 VL 95 IS 2 BP 895 EP 899 DI 10.1172/JCI117740 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA QG209 UT WOS:A1995QG20900060 PM 7860773 ER PT J AU WOODS, GL WITEBSKY, FG AF WOODS, GL WITEBSKY, FG TI MYCOBACTERIAL TESTING IN CLINICAL LABORATORIES THAT PARTICIPATE IN THE COLLEGE-OF-AMERICAN-PATHOLOGISTS MYCOBACTERIOLOGY-E SURVEY - RESULTS OF A 1993 QUESTIONNAIRE SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID TUBERCULOSIS AB Participants in the College of American Pathologists' Mycobacteriology E proficiency testing survey in 1993 were asked to complete a questionnaire addressing mycobacterial test methods, test volume, and frequency of detection of drug-resistant Mycobacterium tuberculosis (MTB). A similar questionnaire had been distributed in 1992. The population responding to the 1993 questionnaire changed, because of a shift of small hospitals to the limited Mycobacteriology E1 survey, and, the format of some questions was altered, so a direct comparison of 1992 and 1993 responses was not always possible. Among participants who answered the questions in both years, there was a significant increase in the use of the fluorochrome stain (57% in 1992, 61% in 1993), BACTEC TB for culture (34% in 1992, 38% in 1993) and susceptibility testing (51% in 1992, 61% in 1993), and DNA probes for identification (30% in 1992, 51% in 1993). The percentage of participants who processed respiratory specimens at least seven times per week increased from 9% in 1992 to 13% in 1993, and the percentage processing five times per week increased from 68 to 72%. The percentage of respondents who reported an identification of MTB within 21 days of specimen receipt and susceptibility test results within 28 days in 1992 and 1993 increased from 30 to 41% and from 12 to 19%, respectively. In regard to resistant MTB, 177 institutions in 1991 and 291 in 1992 reported resistance to isoniazid, and 114 in 1991 and 187 in 1992 reported resistance to both isoniazid and rifampin. Laboratorians are to be applauded for using the more rapid mycobacterial testing methods; however, given that tuberculosis remains a problem, this trend must continue. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,MICROBIOL SERV,BETHESDA,MD 20892. RP WOODS, GL (reprint author), UNIV TEXAS,MED BRANCH,DEPT PATHOL,GALVESTON,TX 77555, USA. NR 12 TC 24 Z9 24 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD FEB PY 1995 VL 33 IS 2 BP 407 EP 412 PG 6 WC Microbiology SC Microbiology GA QC148 UT WOS:A1995QC14800029 PM 7714200 ER PT J AU WILSON, WH CHABNER, BA BRYANT, G BATES, S FOJO, A REGIS, J JAFFE, ES STEINBERG, SM GOLDSPIEL, BR CHESON, BD WITTES, RE AF WILSON, WH CHABNER, BA BRYANT, G BATES, S FOJO, A REGIS, J JAFFE, ES STEINBERG, SM GOLDSPIEL, BR CHESON, BD WITTES, RE TI PHASE-II STUDY OF PACLITAXEL IN RELAPSED NON-HODGKINS-LYMPHOMAS SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; METASTATIC BREAST-CANCER; CELL-LINES; TAXOL; CHEMOTHERAPY; TRIAL AB Purpose: To assess the efficacy and toxicity of paclitaxel administered as a 96-hour infusion to patients with relapsed non-Hodgkin's lymphomas (NHLs). Patients and Methods: Eligible patients had relapsed NHL and measurable disease and were considered incurable. Paclitaxel was infused at a dose of 140 mg/m(2) every 3 weeks. Premedications to prevent paclitaxel hypersensitivity reactions were not administered and no patients received corticosteroids. Expression of the multidrug resistance (mdr-1) gene was determined in tumor from 17 patients by mRNA quantitative polymerase chain reaction (PCR). Results: Thirty-one patients received a total of 99 cycles of paclitaxel. Two patients were not assessable for response. The median age was 50 years, 71% had stage IV disease, and intermediate/high-grade histology was present in 65% of patients. Patients had received a median of three prior chemotherapy regimens, and 68% of patients had responded to the previous chemotherapy (chemotherapy-sensitive). Of 29 assessable patients, five (17%) achieved a partial response (PR). With a median potential follow-up time of 17 months, the median even-free and overall survival durations were 1.6 and 7.5 months, respectively. No correlation was found between response to paclitaxel and extent of prior treatment or response. The mdr-1 gene wets easily detectable in 14 of 17 tumor biopsies, but was low in all but one sample. The most serious toxicity was grade 4 neutropenia, which occurred during 14% of cycles. Conclusion: Paclitaxel was well tolerated, but had a low response rate in patients with relapsed NHLs. There was no clear association between response to paclitaxel and extent of or response to prior treatment. Most patients had chemotherapy-sensitive disease, which suggests that the low response rate to paclitaxel was probably not due to general chemotherapy resistance. Paclitaxel provided good palliation in a minority of patients and is a reasonable agent to consider for use in patients who have failed to respond to standard chemotherapy. RP WILSON, WH (reprint author), NCI,DIV CANC TREATMENT,MED BRANCH,BLDG 31,ROOM 3A44,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 26 TC 61 Z9 61 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 1995 VL 13 IS 2 BP 381 EP 386 PG 6 WC Oncology SC Oncology GA QF298 UT WOS:A1995QF29800011 PM 7531220 ER PT J AU TRAVIS, LB CURTIS, RE HANKEY, BF AF TRAVIS, LB CURTIS, RE HANKEY, BF TI 2ND MALIGNANCIES AFTER TESTICULAR CANCER SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter RP TRAVIS, LB (reprint author), NCI,BETHESDA,MD 20892, USA. NR 3 TC 12 Z9 12 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB PY 1995 VL 13 IS 2 BP 533 EP 534 PG 2 WC Oncology SC Oncology GA QF298 UT WOS:A1995QF29800037 PM 7844617 ER PT J AU LOE, H AF LOE, H TI NIDR - A VIEW FROM THE INSIDE SO JOURNAL OF DENTAL RESEARCH LA English DT Editorial Material C1 NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD FEB PY 1995 VL 74 IS 2 BP 630 EP 633 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA QV531 UT WOS:A1995QV53100003 PM 7722059 ER PT J AU CHAMPOUX, M BOYCE, WT SUOMI, SJ AF CHAMPOUX, M BOYCE, WT SUOMI, SJ TI BIOBEHAVIORAL COMPARISONS BETWEEN ADOPTED AND NONADOPTED RHESUS-MONKEY INFANTS SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE ADOPTION; FOSTER CARE; MENTAL HEALTH; DEVELOPMENT, PRIMATES ID CHILDREN AB Differences between adopted and nonadopted infant rhesus monkeys were examined, as were differences between biological and foster mothers, in measures of infancy and postinfancy behaviors, material-infant interactions, and neuroendocrine and behavioral responses to separations. Newborns were experimentally allocated to continuous postnatal care by either their biological mothers (n = 9) or adoptive, nonbiological mothers (n = 7). Behavioral observations were completed during the neonatal period, during separations at 30 days and 5 months, and from 6 to 18 months of age, when animals were housed in a large social group. Maternal and infant responses to separation stress were assessed using measures of behavioral, adrenocortical, and growth hormone reactivity. Out of 84 possible comparisons, only six achieved statistical significance, a number compatible with the operation of chance. Negligible differences in behavioral and neuroendocrine endpoints were found between adopted and nonadopted mother-infant pairs. These findings lend additional credence to human studies finding no increase in the incidence or severity of mental disorders in adopted children. C1 UNIV CALIF SAN FRANCISCO,DEPT PEDIAT,DIV BEHAV & DEV PEDIAT,SAN FRANCISCO,CA 94143. RP CHAMPOUX, M (reprint author), NICHHD,COMPARAT ETHOL LAB,CTR ANIM,POB 529,POOLESVILLE,MD 20837, USA. NR 22 TC 7 Z9 7 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD FEB PY 1995 VL 16 IS 1 BP 6 EP 13 PG 8 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA QG275 UT WOS:A1995QG27500002 PM 7730459 ER PT J AU ROBBINS, J AF ROBBINS, J TI PROGNOSTIC FACTORS IN THE MANAGEMENT OF THYROID-CANCER SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Article; Proceedings Paper CT International Workshop on Thyroid Cancer - Basic Science and Clinical Problems CY DEC 02-04, 1993 CL TAORMINA, ITALY DE THYROID CANCER; PROGNOSIS; RISK ASSESSMENT; METASTASIS; MORTALITY ID CARCINOMA RP ROBBINS, J (reprint author), NIDDKD,GENET & BIOCHEM BRANCH,ENDOCRINOL SECT,BETHESDA,MD 20892, USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILANO PA VIA LUIGI ZOJA, 30-20153 MILANO, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD FEB PY 1995 VL 18 IS 2 BP 159 EP 160 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QQ437 UT WOS:A1995QQ43700019 PM 7629388 ER PT J AU SETTE, A SOUTHWOOD, S MILLER, J APPELLA, E AF SETTE, A SOUTHWOOD, S MILLER, J APPELLA, E TI BINDING OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II TO THE INVARIANT CHAIN-DERIVED PEPTIDE, CLIP, IS REGULATED BY ALLELIC POLYMORPHISM IN CLASS-II SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HLA-DR MOLECULES; ANTIGEN-PROCESSING MUTANT; MICE LACKING; CELL LINE; CONTAINS; ASSOCIATION; EXPRESSION; TRANSPORT; SEQUENCE; SIGNAL AB Major histocompatibility complex class II-associated invariant chain (Ii) provides several important functions that regulate class II expression and function. One of these is the ability to inhibit class II peptide loading early in biosynthesis. This allows for efficient class II folding and egress from the endoplasmic reticulum, and protects the class II peptide binding site from loading with peptides before entry into endosomal compartments. The ability of Ii to interact with class II and interfere with peptide loading has been mapped to Ii exon 3, which encodes amino acids 82-107. This same region of Ii has been described as a nested set of class II-associated Ii peptides (CLIPs) that are transiently associated with class II in normal cells and accumulate in human histocompatibility leukocyte antigen-DM-negative cell lines. Currently it is not clear how CLIP and the CLIP region of Ii blocks peptide binding. CLIP may bind directly to the class II peptide binding site, or may bind elsewhere on class II and modulate class II peptide binding allosterically. In this report, we show that CLIP can interact with many different murine and human class II molecules, but that the affinity of this interaction is controlled by polymorphic residues in the class II chains. Likewise, structural changes in CLIP also modulate class II binding in an allele-dependent manner. Finally, the specificity and kinetics of CLIP binding to class II molecule is similar to antigenic peptide binding to class II. These data indicate that CLIP binds to class II in an analogous fashion as conventional antigenic peptides, suggesting that the CLIP segment of Ii may actually occupy the class II peptide binding site. C1 UNIV CHICAGO,DEPT MOLEC GENET & CELL BIOL,CHICAGO,IL 60637. NCI,BETHESDA,MD 20892. RP SETTE, A (reprint author), CYTEL CORP,DEPT IMMUNOL,3525 JOHN HOPKINS COURT,SAN DIEGO,CA 92121, USA. FU NIAID NIH HHS [AI-18634] NR 46 TC 165 Z9 165 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 1 PY 1995 VL 181 IS 2 BP 677 EP 683 DI 10.1084/jem.181.2.677 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA QD012 UT WOS:A1995QD01200024 PM 7836921 ER PT J AU SACKS, DL PIMENTA, PFP MCCONVILLE, MJ SCHNEIDER, P TURCO, SJ AF SACKS, DL PIMENTA, PFP MCCONVILLE, MJ SCHNEIDER, P TURCO, SJ TI STAGE-SPECIFIC BINDING OF LEISHMANIA-DONOVANI TO THE SAND FLY VECTOR MIDGUT IS REGULATED BY CONFORMATIONAL-CHANGES IN THE ABUNDANT SURFACE LIPOPHOSPHOGLYCAN SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MAJOR PROMASTIGOTES; DEVELOPMENTAL MODIFICATION; INFECTIVE STAGE; COMPLEMENT; EXPRESSION; GENERATION AB The life cycle of Leishmania parasites within the sand fly vector includes the development of extracellular promastigotes from a noninfective, procyclic stage into an infective, metacyclic stage that is uniquely adapted for transmission by the fly and survival in the vertebrate host. These adaptations were explored in the context of the structure and function of the abundant surface lipophosphoglycan (LPG) on Leishmania donovani promastigotes. During metacyclogenesis, the salient structural feature oft, donavani LPG is conserved, involving expression of a phosphoglycan chain made up of unsubstituted disaccharide-phosphate repeats. Two important developmental modifications were also observed. First, the size of the molecule is substantially increased because of a twofold increase in the number of phosphorylated disaccharide repeat units expressed. Second, there is a concomitant decrease in the presentation of terminally exposed sugars. This later property was indicated by the reduced accessibility of terminal galactose residues to galactose oxidase and the loss of binding by the lectins, peanut agglutinin, and concanavalin A, to metacyclic LPG in vivo and in vitro. The loss of lectin binding was not due to downregulation of the capping oligosaccharides as the same P-linked galactose or cu-linked mannose-terminating oligosaccharides were present in both procyclic and metacyclic promastigotes. The capping sugars on procyclic LPG were found to mediate procyclic attachment to the sand fly midgut, whereas these same sugars on metacyclic LPG failed to mediate metacyclic binding. And whereas intact metacyclic LPG did not inhibit procyclic attachment, depolymerized LPG inhibited as well as procyclic LPG, demonstrating that the ligands are normally buried. The masking of the terminal sugars is attributed to folding and clustering of the extended phosphoglycan chains, which form densely distributed particulate structures visible on fracture-flip preparations of the metacyclic surface. The exposure and subsequent masking of the terminal capping sugars explains the stage specificity of promastigote attachment to and release from the vector midgut, which are key events in the development of transmissible infections in the fly. C1 UNIV DUNDEE,DEPT BIOCHEM,DUNDEE DD1 4HN,SCOTLAND. UNIV KENTUCKY,MED CTR,DEPT BIOCHEM,LEXINGTON,KY 40536. RP SACKS, DL (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [AI-20941]; Wellcome Trust NR 27 TC 126 Z9 129 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 1 PY 1995 VL 181 IS 2 BP 685 EP 697 DI 10.1084/jem.181.2.685 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA QD012 UT WOS:A1995QD01200025 PM 7836922 ER PT J AU WANG, RF ROBBINS, PF KAWAKAMI, Y KANG, XQ ROSENBERG, SA AF WANG, RF ROBBINS, PF KAWAKAMI, Y KANG, XQ ROSENBERG, SA TI IDENTIFICATION OF A GENE ENCODING A MELANOMA TUMOR-ANTIGEN RECOGNIZED BY HLA-A31-RESTRICTED TUMOR-INFILTRATING LYMPHOCYTES SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID TYROSINASE-RELATED PROTEIN; METASTATIC MELANOMA; BROWN LOCUS; T-CELLS; MOUSE; INTERLEUKIN-2; IMMUNOTHERAPY; CDNA; MAPS; CANCER AB The availability of antitumor cytotoxic T lymphocytes which can be generated from either peripheral blood lymphocytes after stimulation in vitro or tumor infiltrating lymphocytes (TIL) has made it possible to identify a number of melanoma antigens presented by major histocompatibility complex class I molecules. The present and previous studies indicated that TIL586 recognized an antigen expressed on most melanoma and normal melanocytes in the context of the HLA-A31 molecule. We report here the cloning of a cDNA that directs the expression of the shared melanoma antigen recognized by this TIL. The DNA sequence analysis revealed that the cDNA was almost identical to the gene encoding tyrosinase-related protein 1 or glycoprotein gp75 which was originally identified by serum antibodies in a patient with melanoma. The gene was found to be expressed only in melanoma, normal melanocyte cell lines, and retina, but not in other normal tissues tested. The gp75 antigen presented by HLA-A31 may therefore constitute a useful immune target for specific treatment of patients with melanoma, since both antibody- and T cell-mediated immune responses can be generated against this antigen. RP WANG, RF (reprint author), NCI,SURG BRANCH,BLDG 10,2B42,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 NR 35 TC 240 Z9 240 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 1 PY 1995 VL 181 IS 2 BP 799 EP 804 DI 10.1084/jem.181.2.799 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA QD012 UT WOS:A1995QD01200038 PM 7836932 ER PT J AU CAVANI, A HACKETT, CJ WILSON, KJ ROTHBARD, JB KATZ, SI AF CAVANI, A HACKETT, CJ WILSON, KJ ROTHBARD, JB KATZ, SI TI CHARACTERIZATION OF EPITOPES RECOGNIZED BY HAPTEN-SPECIFIC CD4(+) T-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EPIDERMAL LANGERHANS CELLS; IMMUNOGENIC PEPTIDES; CONTACT SENSITIVITY; IA; ANTIGEN; SKIN; ACTIVATION; MOLECULES; INDUCTION AB Although protein-derived nominal Ags have, in many instances, been precisely determined, the epitopes recognized by hapten-specific CD4(+) T cells responsible for contact sensitization have not been defined. To better understand the nature of the precise epitopes generated after hapten interaction with Langerhans cells (LC), we assessed the ability of TNP-modified I-A(k)- and I-A(u)-binding peptides to activate hapten-specific CD4(+) T cells obtained respectively from TNCB-primed C3H (H-2(k)) and PL/j (H-2(u)) mice. Using LC as APC, I-A(k)-restricted TNP-specific CD4(+) T cells proliferated in the presence of the synthetic peptide hen egg lysozyme 52-61 derivatized with TNP at position 56, and less so when TNP was coupled at positions 53 or 59. Similarly, I-A(u)-restricted TNP-specific CD4(+) T cells from PL/j mice were triggered by the synthetic I-A(u)-binding 13 mer poly(A)-Y5-R6 TNP-modified at position 4, and to a limited extent with TNP coupled in positions 7 or 10. Our results indicate that hapten-modified MHC class II binding nonautologous peptides are recognized by hapten-specific CD4(+) T cells and that precise positioning of hapten molecules on peptides binding MHC class II molecules is required for optimal CD4(+) T cell recognition. These findings provide insight into the manner in which haptens are recognized by T cells involved in contact sensitivity and should facilitate the study and design of specific therapies for the manipulation of hapten-specific CD4(+) T cell responses. C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. IMMULOG PHARMACEUT CORP,PALO ALTO,CA 94304. OI Hackett, Charles/0000-0003-4586-9669 NR 34 TC 68 Z9 74 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 1995 VL 154 IS 3 BP 1232 EP 1238 PG 7 WC Immunology SC Immunology GA QC546 UT WOS:A1995QC54600027 PM 7529797 ER PT J AU LIVINGSTON, PG KURANE, I DAI, LC OKAMOTO, Y LAI, CJ MEN, R KARAKI, S TAKIGUCHI, M ENNIS, FA AF LIVINGSTON, PG KURANE, I DAI, LC OKAMOTO, Y LAI, CJ MEN, R KARAKI, S TAKIGUCHI, M ENNIS, FA TI DENGUE VIRUS-SPECIFIC, HLA-B35-RESTRICTED, HUMAN CD8(+) CYTOTOXIC T-LYMPHOCYTE (CTL) CLONES - RECOGNITION OF NS3 AMINO-ACID-500 TO AMINO-ACID-508 BY CTL CLONES OF 2 DIFFERENT SEROTYPE SPECIFICITIES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERFERON GAMMA-PRODUCTION; RECOMBINANT VACCINIA VIRUS; NONSTRUCTURAL PROTEIN-NS1; CHORIOMENINGITIS VIRUS; MONOCLONAL-ANTIBODIES; STRUCTURAL PROTEINS; NUCLEOTIDE-SEQUENCE; MOLECULAR ANALYSIS; CELL CLONES; MICE AB Dengue virus infections are a major cause of morbidity and mortality in tropical and subtropical areas of the world. We analyzed dengue virus-specific CD8(+) CD4(-) CTL at the clonal level to further understand the role of CD8(+) CTL in dengue virus infections. Dengue virus-specific CD8(+) CTL clones were established from lymphocytes of a dengue 4-immune adult. Three patterns of dengue serotype specificities were identified: 1) specific for dengue 4, 2) cross-reactive for dengue 2 and dengue 4 (subcomplex-specific); and 3) cross-reactive for all four dengue virus serotypes. Three dengue 4-specific clones and one dengue 2/dengue 4 cross-reactive clone were further analyzed. All four of the clones were HLA-B35 restricted and recognized NS3. The epitopes were mapped to amino acids (aa) 483 to 618 of NS3. The epitope was then defined by using synthetic peptides. Three dengue 4-specific clones and one dengue 2/dengue 4 cross-reactive clone recognized the same peptide (TPEGIIPTL) encompassing aa 500 to 508 of dengue 4 NS3. The peptide encompassing aa 500-508 of dengue 2 NS3 was recognized by a dengue 2/dengue 4 cross-reactive clone but was not recognized by the dengue 4-specific clones. Dengue 4-specific and dengue 2/dengue 4 cross-reactive clones used different TCR. These results indicate that CD8(+) CTL clones that use different TCR and demonstrate two distinct serotype specificities recognize the same 9-mer peptide in the context of HLA-B35. C1 UNIV MASSACHUSETTS,MED CTR,DEPT MED,DIV INFECT DIS & IMMUNOL,WORCESTER,MA 01655. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. UNIV TOKYO,INST MED SCI,DEPT TUMOR BIOL & IMMUNOL,TOKYO 108,JAPAN. RI Takiguchi, Masafumi/E-7468-2013 FU NIAID NIH HHS [R01-AI30624, T32-AI 07272] NR 54 TC 65 Z9 67 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 FEB 1 PY 1995 VL 154 IS 3 BP 1287 EP 1295 PG 9 WC Immunology SC Immunology GA QC546 UT WOS:A1995QC54600034 PM 7529799 ER PT J AU SGAGIAS, MK GAGNETON, DC ROSENBERG, SA DANFORTH, DN AF SGAGIAS, MK GAGNETON, DC ROSENBERG, SA DANFORTH, DN TI CELLULAR CHARACTERIZATION AND RETROVIRAL TRANSDUCTION OF SHORT-TERM BREAST-CANCER CELLS SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE HUMAN MAMMARY CARCINOMA; DF3 ANTIGEN; RETROVIRAL TRANSDUCTION ID MAMMARY EPITHELIAL-CELLS; CARCINOMA-ASSOCIATED ANTIGEN; MONOCLONAL-ANTIBODY DF3; CARCINOEMBRYONIC ANTIGEN; GAMMA-INTERFERON; GENE-TRANSFER; EXPRESSION; LINES; GROWTH; TRANSCRIPTION AB The effort to develop cell lines from surgical specimens has been a difficult goal for years. We derived short-term primary human mammary carcinoma cell lines from breast tumors in 20 of 23 patients. Morphologically, cultured cells showed small cells with high nuclear cytoplasmic ratio and larger cells with abundant dense cytoplasm. The nuclei were round to oval with one to four nucleoli. Immunocytochemically, the cells stained positive for keratin. Tumor cells showed phenotypic overexpression of the breast tumor-associated antigen DF3 compared with normal mammary epithelial cells. The doubling time of tumor cells in vitro ranged from 2.6 to 3.6 days. The cultured cells were characterized as mammary carcinoma cells by their tumorigenicity in nude mice. Of 14 of the 23 short-term cell lines tested, 5 grew in nude mice and eventually regressed, 3 grew progressively in nude mice, and the remaining 6 did not grow within 3 months. To examine the feasibility of cytokine gene transfer into human mammary carcinoma cells, we introduced the cDNA for human tumor necrosis factor-alpha. (TNF-alpha) into short-term cell lines with a retroviral vector. In our short-term primary breast cancer cell lines derived from breast tumors, TNF-alpha secretion ranged between 89 ng/10(6) cells/48 h and 479 ng/10(6) cells/24 h. These findings indicate that short-term primary human mammary carcinoma cell lines can be grown consistently from breast tumors, and that retroviral mediated-cytokine gene transfer into short-term human mammary carcinoma cells is feasible and may be of potential use in immunotherapy trials. C1 NIH,SURG BRANCH,BETHESDA,MD 20892. NIH,PATHOL LAB,BETHESDA,MD 20892. NR 33 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD FEB PY 1995 VL 17 IS 2 BP 88 EP 97 DI 10.1097/00002371-199502000-00003 PG 10 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA QP341 UT WOS:A1995QP34100003 PM 7647960 ER PT J AU SECCHIERO, P CARRIGAN, DR ASANO, Y BENEDETTI, L CROWLEY, RW KOMAROFF, AL GALLO, RC LUSSO, P AF SECCHIERO, P CARRIGAN, DR ASANO, Y BENEDETTI, L CROWLEY, RW KOMAROFF, AL GALLO, RC LUSSO, P TI DETECTION OF HUMAN HERPESVIRUS-6 IN PLASMA OF CHILDREN WITH PRIMARY INFECTION AND IMMUNOSUPPRESSED PATIENTS BY POLYMERASE CHAIN-REACTION SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CHRONIC FATIGUE SYNDROME; BONE-MARROW TRANSPLANTATION; NATURAL-KILLER-CELLS; EXANTHEM-SUBITUM; IMMUNOLOGICAL ABNORMALITIES; VIRUS; BLOOD; DNA; IDENTIFICATION; POLYMORPHISM AB A sensitive and specific polymerase chain reaction method for the detection of human herpesvirus 6 (HHV-6) DNA in serum or plasma has been developed. In total, 157 human serum or plasma samples were studied. HHV-6 DNA was detected in 6 (85.7%) of 7 children with exanthem subitum, 3 (23.1%) of 13 bone marrow transplant (BMT) recipients, 4 (22.2%) of 18 human immunodeficiency virus (HIV)-infected patients, 1 (2.6%) of 39 patients with chronic fatigue syndrome, and none of 37 healthy adults. In the HHV-6-positive BMT recipients, HHV-6 plasma DNA was transiently detected during episodes of fever and respiratory infection. In children with exanthem subitum and in 1 HIV-infected patient, the HHV-6 strains were characterized as variant B, whereas variant A was detected in all other patients. Detection of viral DNA in serum or plasma is a marker of active infection that can be used to investigate the role of HHV-6 in human disease. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. MED COLL WISCONSIN,DEPT PATHOL,MILWAUKEE,WI 53226. FUJITA HLTH UNIV,SCH MED,DEPT PEDIAT,TAYOAKE,JAPAN. UNIV ROMA LA SAPIENZA,INST HYSTOL & GEN EMBRYOL,ROME,ITALY. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV GEN MED & PRIMARY CARE,BOSTON,MA 02115. RI Asano, Yoshizo/F-6870-2012; secchiero, paola/G-9689-2015 OI secchiero, paola/0000-0003-4101-7987 NR 51 TC 232 Z9 240 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB PY 1995 VL 171 IS 2 BP 273 EP 280 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA QF229 UT WOS:A1995QF22900002 PM 7844362 ER PT J AU REICHMAN, RC MORSE, GD DEMETER, LM RESNICK, L BASSIAKOS, Y FISCHL, M PARA, M POWDERLY, W LEEDOM, J GREISBERGER, C NEVIN, T WOOD, K MEEHAN, PM GEHEB, H COX, S BATTS, D TIMPONE, J SLACK, A ROYAL, M QUESADA, NR GEISELER, PJ STARK, N NEIDIG, J HILL, M AF REICHMAN, RC MORSE, GD DEMETER, LM RESNICK, L BASSIAKOS, Y FISCHL, M PARA, M POWDERLY, W LEEDOM, J GREISBERGER, C NEVIN, T WOOD, K MEEHAN, PM GEHEB, H COX, S BATTS, D TIMPONE, J SLACK, A ROYAL, M QUESADA, NR GEISELER, PJ STARK, N NEIDIG, J HILL, M TI PHASE-I STUDY OF ATEVIRDINE, A NONNUCLEOSIDE REVERSE-TRANSCRIPTASE INHIBITOR, IN COMBINATION WITH ZIDOVUDINE FOR HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CONTROLLED TRIAL; HIV-1 REPLICATION; RESISTANCE; DIDEOXYCYTIDINE; DERIVATIVES; CULTURE; POTENT AB Twenty patients were enrolled in a phase I clinical trial of atevirdine, a nonnucleoside reverse transcriptase inhibitor (NNRTI), given in combination with zidovudine for treatment of human immunodeficiency virus type 1 (HIV-1) infection. Fifteen patients had received no previous antiretroviral therapy. HIV-1 isolates obtained at 6-week intervals were tested for sensitivity to atevirdine and zidovudine. Two patients developed a rash within 2 weeks of enrollment, and 1 of these developed concomitant fever and hepatitis. No hematopoietic, neurologic, or pancreatic toxicities were observed. Atevirdine had considerable initial interpatient pharmacokinetic variability. Forty-seven percent of patients treated with atevirdine plus zidovudine had increased CD4 lymphocyte counts, and HIV isolates from 62% of patients remained sensitive to atevirdine after 24 weeks of therapy. Atevirdine plus zidovudine was well-tolerated. Additional studies should be done to determine the role of atevirdine in the therapy for HIV infection. C1 SUNY BUFFALO,DEPT PHARM,BUFFALO,NY. SUNY BUFFALO,DEPT MED,BUFFALO,NY. STAT DATA ANAL CTR,AMHERST,NY. UNIV MIAMI,DEPT MED,MIAMI,FL. WASHINGTON UNIV,ST LOUIS,MO. NIAID,BETHESDA,MD. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. UNIV SO CALIF,DEPT MED,INFECT DIS SECT,LOS ANGELES,CA. UPJOHN CO,KALAMAZOO,MI 49001. OHIO STATE UNIV,DEPT INFECT DIS,COLUMBUS,OH 43210. RP REICHMAN, RC (reprint author), UNIV ROCHESTER,SCH MED & DENT,DEPT MED,INFECT DIS UNIT,601 ELMWOOD AVE,BOX 689,ROCHESTER,NY 14642, USA. FU NIAID NIH HHS [AI-27658, AI-27675, AI-25924] NR 29 TC 17 Z9 17 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB PY 1995 VL 171 IS 2 BP 297 EP 304 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA QF229 UT WOS:A1995QF22900005 PM 7531207 ER PT J AU ARANKALLE, VA TSAREV, SA CHADHA, MS ALLING, DW EMERSON, SU BANERJEE, K PURCELL, RH AF ARANKALLE, VA TSAREV, SA CHADHA, MS ALLING, DW EMERSON, SU BANERJEE, K PURCELL, RH TI AGE-SPECIFIC PREVALENCE OF ANTIBODIES TO HEPATITIS-A AND HEPATITIS-E VIRUSES IN PUNE, INDIA, 1982 AND 1992 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID NON-A; NON-B; INFECTION AB The age-specific seroprevalence of antibody to hepatitis A virus (HAV) and antibody to hepatitis E virus (HEV) were studied in persons in Pune, India, where both viruses are endemic. The data showed that HAV infected the majority of persons by age 3 years and virtually 100% by late childhood. In contrast, infection with HEV was rare in children and did not reach peak prevalence (33%-40%) until early adulthood. The reason for the differences in infection rates between HAV and HEV is not known. Age-specific antibody patterns in serum samples obtained 10 years apart show that neither HAV nor HEV has diminished in medical importance in this Indian community. C1 NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892. NIAID,OFF DIRECTOR,BETHESDA,MD 20892. INDIAN COUNCIL MED RES,NATL INST VIROL,POONA,MAHARASHTRA,INDIA. FU NIAID NIH HHS [AI-05069] NR 15 TC 204 Z9 209 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB PY 1995 VL 171 IS 2 BP 447 EP 450 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA QF229 UT WOS:A1995QF22900029 PM 7844387 ER PT J AU SHI, XL MAO, Y AHMED, N JIANG, HG AF SHI, XL MAO, Y AHMED, N JIANG, HG TI HPLC INVESTIGATION ON NI(II)-MEDIATED DNA-DAMAGE IN THE PRESENCE OF T-BUTYL HYDROPEROXIDE AND GLUTATHIONE SO JOURNAL OF INORGANIC BIOCHEMISTRY LA English DT Article ID LIPID-PEROXIDATION PRODUCTS; RADICAL GENERATION; HYDROGEN-PEROXIDE; NICKEL CHLORIDE; ESR EVIDENCE; L-HISTIDINE; TOXICITY; RATS; CARCINOGENICITY; SYSTEMS AB By use of HPLC with UV and electrochemical detection, the present study demonstrates that reaction of Ni2+ with t-butyl hydroperoxide in the presence of glutathioine (GSH) generates 8-hydroxy-2'-deoxyguanosine (8-OH-dG) from 2'-deoxyguanosine (dG) and from dG residues in calf thymus DNA at physiological pH. No significant amount of 8-OH-dG was generated in the absence of GSH, indicating an important role of GSH in enhancing the reactivity of Ni2+ toward lipid hydroperoxide to oxidize dG or dG residues in DNA. The rate of dG conversion to 8-OH-dG depends on the concentration of the reagents. During a two hour incubation of 0.75 mM dG, 10 mM t-butyl hydroperoxide, 1 mM Ni2+, and 2 mM GSH at room temperature under ambient air, dG was converted to 8-OH-dG with a yield of about 0.2%. For dG residues in DNA, 24 hour incubation at 37 degrees C yielded 0.1% 8-OH-dG. The 8-OH-dG generation from both dG and dG residues in DNA was inhibited by superoxide dismutase, catalase, and ethanol (hydroxyl radical scavenger), implying the involvement of oxygen free radicals in the 8-OH-dG generation process. The metal ion chelators, deferoxamine and EDTA, efficiently inhibited the 8-OH-dG formation. Similar results were obtained for the conversion of dG residues in calf thymus DNA to 8-OH-dG. Electrophoretic assays of DNA strand breaks showed that Ni2+ caused DNA double-strand breaks in the presence of t-butyl hydroperoxide and GSH. Because GSH is ubiquitously present in cellular systems at relatively high concentration, and the exposure of cells to Ni2+ results in the generation of lipid hydroperoxides, the 8-OH-dG generation and DNA double-strand breaks caused by the reaction of Ni2+ with lipid hydroperoxides in the presence of GSH may be an important mechanism in Ni2+-induced carcinogenesis. The inhibitory effect of chelators suggests a possible prevention strategy against Ni2+-induced toxicity and carcinogenesis. C1 FREDERICK CANC RES & DEV CTR,ENVIRONM CONTROL & RES PROGRAM,FREDERICK,MD. RP SHI, XL (reprint author), NCI,EXPTL PATHOL LAB,BLDG 41,ROOM C301,BETHESDA,MD 20892, USA. RI Shi, Xianglin/B-8588-2012 NR 36 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0162-0134 J9 J INORG BIOCHEM JI J. Inorg. Biochem. PD FEB PY 1995 VL 57 IS 2 BP 91 EP 102 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA QC770 UT WOS:A1995QC77000002 PM 7861128 ER PT J AU DOMANSKI, MJ AF DOMANSKI, MJ TI SUDDEN CARDIAC DEATH PREVENTION - ANTIARRHYTHMIC DRUGS AND THE IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR SO JOURNAL OF INTERVENTIONAL CARDIOLOGY LA English DT Article RP DOMANSKI, MJ (reprint author), NHLBI,CLIN TRIALS BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 SN 0896-4327 J9 J INTERV CARDIOL JI J. Interv. Cardiol. PD FEB PY 1995 VL 8 IS 1 BP 9 EP 15 DI 10.1111/j.1540-8183.1995.tb00505.x PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA QJ609 UT WOS:A1995QJ60900003 PM 10155222 ER PT J AU KIM, SY CHUNG, SI YONEDA, K STEINERT, PM AF KIM, SY CHUNG, SI YONEDA, K STEINERT, PM TI EXPRESSION OF TRANSGLUTAMINASE-1 IN HUMAN EPIDERMIS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID CORNIFIED CELL-ENVELOPE; KERATINOCYTE TRANSGLUTAMINASE; HUMAN LORICRIN; INTERMEDIATE FILAMENTS; PROTRANSGLUTAMINASE-E; DIFFERENTIATION; GENE; PROTEIN; MOUSE; SKIN AB To explore the expression and function of the membrane-associated or type I transglutaminase (TGase1) in human epidermis, we have made a new antihuman TGase1 antibody in goats elicited against a purified active recombinant protein expressed in bacteria, By use of Western blotting and immunoprecipitation methods, the antibody reacted with high specificity with only the TGase1 activity of the epidermis and in cultured keratinocytes, By indirect immunofluorescence, the antibody decorated the entire epidermis, including the basal layer, with some potentiation of the granular layer, However, these staining properties are quite different from those of a widely used, commercially available TGase1 monoclonal antibody (termed B.C1), which decorates the granular layers of the epidermis, By Western blotting, it identifies the TGase1 protein band only weakly, but recognizes strongly a group of bands of 15-20 kDa, two of which by amino acid analysis and amino acid sequencing are the small proline-rich (SPR) 1 and SPR2 proteins, also expressed in epidermal and epithelial tissues, Together with a series of blocking experiments with TGase1 proteins and synthetic peptides, these data reveal that the major epitope of the B.C1 antibody most likely resides on the amino-terminus of these two SPR proteins rather than on TGase1. Further studies will now be necessary to determine the role(s) of TGase1 during the different stages of development and differentiation in the epidermis. C1 NIAMSD,SKIN BIOL BRANCH,BETHESDA,MD 20892. NIDR,CELLULAR DEV & ONCOGENESIS LAB,BETHESDA,MD. KYOTO UNIV,FAC MED,DEPT DERMATOL,KYOTO,JAPAN. NR 45 TC 82 Z9 83 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD FEB PY 1995 VL 104 IS 2 BP 211 EP 217 DI 10.1111/1523-1747.ep12612769 PG 7 WC Dermatology SC Dermatology GA QD424 UT WOS:A1995QD42400008 PM 7530270 ER PT J AU BLAUVELT, A KATZ, SI UDEY, MC AF BLAUVELT, A KATZ, SI UDEY, MC TI HUMAN LANGERHANS CELLS EXPRESS E-CADHERIN SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE ADHESION; KERATINOCYTES ID ADHESION MOLECULES AB Murine Langerhans cells (LC) synthesize and express E-cadherin, a Ca++-dependent homophilic cell adhesion molecule that mediates LC-keratinocyte (KC) binding in vitro. In vivo, E-cadherin expression by LC may promote localization and persistence of LC within the epidermis through LC-KC adhesion. In addition, changes in LC E-cadherin expression or affinity may be an important factor in the egress of LC from the epidermis after exposure to antigen. The aim of the present study was to determine if human LC also express E-cadherin. Suction blister roofs were obtained from normal volunteers and epidermal cell (EC) suspensions were prepared by limited trypsinization in the presence of 1 nM Ca++. EC were then incubated with antibodies to E-cadherin and CD1a or HLA-DR, and examined by two-color analytical flow cytometry or immunofluorescence microscopy. Most (82.9% +/- 7.4% [mean +/- SD], range 67-89%, n = 7) freshly prepared human LC expressed E-cadherin, as did the majority of KC. The amount of E-cadherin (as determined by mean fluorescence intensity) expressed by LC and KC was similar. Trypsin/EDTA treatment of freshly prepared EC abrogated expression of E-cadherin by LC and KC, whereas E-cadherin was not degraded by trypsin in the presence of Ca++. LC expressed lower levels of E-cadherin after 3 d in culture. Thus, human LC, like murine LC, express the homophilic adhesion molecule E-cadherin, which may be important in establishing and maintaining interactions between LC and KC in mammalian epidermis. RP BLAUVELT, A (reprint author), NCI,DERMATOL BRANCH,BLDG 10,ROOM 12N238,BETHESDA,MD 20892, USA. NR 13 TC 61 Z9 61 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD FEB PY 1995 VL 104 IS 2 BP 293 EP 296 DI 10.1111/1523-1747.ep12612830 PG 4 WC Dermatology SC Dermatology GA QD424 UT WOS:A1995QD42400023 PM 7829887 ER PT J AU XU, LL KELVIN, DJ YE, GQ TAUB, DD BENBARUCH, A OPPENHEIM, JJ WANG, JM AF XU, LL KELVIN, DJ YE, GQ TAUB, DD BENBARUCH, A OPPENHEIM, JJ WANG, JM TI MODULATION OF IL-8 RECEPTOR EXPRESSION ON PURIFIED HUMAN T-LYMPHOCYTES IS ASSOCIATED WITH CHANGED CHEMOTACTIC RESPONSES TO IL-8 SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE T LYMPHOCYTES; INTERLEUKIN-8; IL-8 RECEPTORS; CHEMOTAXIS ID PERIPHERAL-BLOOD LYMPHOCYTES; HUMAN INTERLEUKIN-8 RECEPTOR; CYTOKINE FAMILY; HUMAN-MONOCYTES; CELLS; BINDING; CD4+; IDENTIFICATION; MIP-1-ALPHA; MIP-1-BETA AB Interleukin-8 is a member of the chemokine superfamily and is a major mediator of acute inflammation. Although IL-8 has been reported by some laboratories also to be a chemoattractant for T lymphocytes, this has been difficult to confirm and remains a controversial issue. By using freshly purified human T cells (90-95 % CD3(+)), we could demonstrate consistent directional migration of T cells to recombinant human IL-8. IL-8 was as potent as RANTES, MIP1 alpha, and MIP1 beta in inducing T cell chemotaxis. Highly purified T cells, however, incubated at 37 degrees C for more than 12 h or cultured overnight with anti-CD3 antibody cross-linked to plastic dishes, showed a markedly reduced capacity to migrate in response to IL-8. This was associated with a decrease in binding of radioiodinated IL-8 to T cells. Northern blot and polymerase chain reaction analyses showed that freshly purified T cells expressed mRNA for both IL-8 receptor type A and type B. Steady-state levels of mRNA for the IL-8RA and IL-8RB genes were also reduced by incubation of the cells with or without anti-CD3 for 12 h at 37 degrees C. These results indicate that T cells are indeed one of the target cell populations for IL-8. The regulation of IL-8 receptor expression on T lymphocytes may contribute to the pathophysiological role of IL-8 in inducing the homing and infiltration of T cells. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,CLIN SERV PROGRAM,FREDERICK,MD 21702. YES BIOTECH LABS,MISSISSAUGA,ON,CANADA. NR 31 TC 59 Z9 60 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD FEB PY 1995 VL 57 IS 2 BP 335 EP 342 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA QF778 UT WOS:A1995QF77800022 PM 7852848 ER PT J AU REMALEY, AT SCHUMACHER, UK AMOUZADEH, HR BREWER, HB HOEG, JM AF REMALEY, AT SCHUMACHER, UK AMOUZADEH, HR BREWER, HB HOEG, JM TI IDENTIFICATION OF NOVEL DIFFERENTIALLY EXPRESSED HEPATIC GENES IN CHOLESTEROL-FED RABBITS BY A NON-TARGETED GENE APPROACH SO JOURNAL OF LIPID RESEARCH LA English DT Article DE NUTRITION; LIVER; GENE; REGULATION; ATHEROSCLEROSIS ID MESSENGER-RNA; MEMBRANE-FUNCTION; KUPFFER CELLS; ATHEROSCLEROSIS; OSTEOPONTIN; HYPERCHOLESTEROLEMIA; LIVER; ATHEROGENESIS; HEPATOCYTES; MACROPHAGES AB Several key genes involved in cholesterol metabolism are known to be directly regulated by cholesterol. The possible indirect effect, however, of increased levels of cellular cholesterol on gene expression and its possible role in cholesterol metabolism and atherosclerosis has not been thoroughly explored. In order to determine the overall effect of cholesterol on gene expression, we isolated differentially expressed genes from a PCR-based subtraction library prepared from the liver of chow-fed and cholesterol-fed rabbits. A total of nine upregulated and four down-regulated cDNA fragments were isolated. As determined by Northern blot analysis, the expression of the isolated cDNAs began to change as early as the first week on the cholesterol-rich diet or as late as 4 weeks, which corresponded with hepatic cholesterol accumulation. Three of the cDNAs were identified by DNA sequence homology, whereas the remaining cDNAs had no significant homology match. CYP1A1, a cytochrome P450 isoenzyme, was found to be downregulated in hepatocytes by cholesterol feeding. Osteopontin and Mac-2, which are produced by macrophages, were found to be up-regulated in Kupffer cells by cholesterol feeding. Overall these results demonstrate the usefulness of the subtraction library approach for identifying new RP REMALEY, AT (reprint author), NHLBI,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 41 TC 11 Z9 11 U1 0 U2 1 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD FEB PY 1995 VL 36 IS 2 BP 308 EP 314 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QH014 UT WOS:A1995QH01400010 PM 7751818 ER PT J AU BYRD, RA DIGENNARO, FS AF BYRD, RA DIGENNARO, FS TI A REAL-TIME IN-LINE RF PULSE SEQUENCE AND ACQUISITION MONITOR FOR NMR SPECTROMETERS SO JOURNAL OF MAGNETIC RESONANCE SERIES A LA English DT Note ID SPECTROSCOPY; SENSITIVITY; SUPPRESSION C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702. RP BYRD, RA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702, USA. RI Byrd, R. Andrew/F-8042-2015 OI Byrd, R. Andrew/0000-0003-3625-4232 NR 7 TC 1 Z9 1 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 1064-1858 J9 J MAGN RESON SER A JI J. Magn. Reson. Ser. A PD FEB PY 1995 VL 112 IS 2 BP 250 EP 254 DI 10.1006/jmra.1995.1040 PG 5 WC Physics, Atomic, Molecular & Chemical SC Physics GA QG806 UT WOS:A1995QG80600017 ER PT J AU AREPALLI, SR GLAUDEMANS, CPJ DAVES, GD KOVAC, P BAX, A AF AREPALLI, SR GLAUDEMANS, CPJ DAVES, GD KOVAC, P BAX, A TI IDENTIFICATION OF PROTEIN-MEDIATED INDIRECT NOE EFFECTS IN A DISACCHARIDE-FAB' COMPLEX BY TRANSFERRED ROESY SO JOURNAL OF MAGNETIC RESONANCE SERIES B LA English DT Note ID RELAXATION-MATRIX ANALYSIS; EXCHANGE; CONFORMATIONS; SPECTROSCOPY; SUPPRESSION; MOLECULES; ANTIBODY C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. NR 21 TC 71 Z9 71 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 1064-1866 J9 J MAGN RESON SER B JI J. Magn. Reson. Ser. B PD FEB PY 1995 VL 106 IS 2 BP 195 EP 198 DI 10.1006/jmrb.1995.1033 PG 4 WC Physics, Atomic, Molecular & Chemical SC Physics GA QE360 UT WOS:A1995QE36000015 PM 7850188 ER PT J AU ZADUNAISKY, JA CARDONA, S AU, L ROBERTS, DM FISHER, E LOWENSTEIN, B CRAGOE, EJ SPRING, KR AF ZADUNAISKY, JA CARDONA, S AU, L ROBERTS, DM FISHER, E LOWENSTEIN, B CRAGOE, EJ SPRING, KR TI CHLORIDE TRANSPORT ACTIVATION BY PLASMA OSMOLARITY DURING RAPID ADAPTATION TO HIGH SALINITY OF FUNDULUS-HETEROCLITUS SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article; Proceedings Paper CT Membaires Symposium CY APR 06-09, 1994 CL BUENOS AIRES, ARGENTINA DE GILL CHLORIDE CELL; CL- SECRETION; FUNDULUS HETEROCLITUS; CELL VOLUME REGULATION; NA+/H+ EXCHANGER; CL-/HCO3-; EXCHANGER ID MEMBRANE NA+; EPITHELIUM; CELL; MECHANISMS; DECREASE; VOLUME AB Transition from low salt water to sea water of the euryhaline fish, Fundulus heteroclitus, involves a rapid signal that induces salt secretion by the gill chloride cells. An increase of 65 mOsm in plasma osmolarity was found during the transition. The isolated, chloride-cell-rich opercular epithelium of sea-water-adapted Fundulus exposed to 50 mOsm mannitol on the basolateral side showed a 100% increase in chloride secretion, which was inhibited by bumetanide 10(-4) M and 10(-4) M DPC (N-Phenylanthranilic acid). No effect of these drugs was found on apical side exposure. A Na+/H+ exchanger, demonstrated by NH4Cl exposure, was inhibited by amiloride and its analogues and stimulated by IBMX, phorbol eaters, and epithelial growth factor (EGF). Inhibition of the Na+/H+ exchanger blocks the chloride secretion increase due to basolateral hypertonicity. A Cl-/HCO3- exchanger was also found in the chloride cells, inhibited by 10(-4) M DIDS but not involved in the hyperosmotic response. Ca2+ concentration in the medium was critical for the stimulation of Cl- secretion to occur. Chloride cell volume shrinks in response to hypertonicity of the basolateral side in sea-water-adapted operculi; no effect was found on the apical side. Freshwater-adapted fish chloride cells show increased water permeability of the apical side. It is concluded that the rapid signal for adaptation to higher salinities is an increased tonicity of the plasma that induces chloride cell shrinkage, increased chloride secretion with activation of the Na(+)K(+)2Cl(-) cotransporter, the Na+/H+ exchanger and opening of Cl- channels. C1 NYU,MED CTR,DEPT OPHTHALMOL,NEW YORK,NY 10016. MT DESERT ISL BIOL LAB,SALSBURY COVE,ME 04672. NIH,KIDNEY & ELECTROLYTE LAB,BETHESDA,MD 20892. RP ZADUNAISKY, JA (reprint author), NYU,MED CTR,DEPT PHYSIOL & BIOPHYS,550 1ST AVE,NEW YORK,NY 10016, USA. FU NEI NIH HHS [EYO1340] NR 24 TC 73 Z9 76 U1 2 U2 12 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD FEB PY 1995 VL 143 IS 3 BP 207 EP 217 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA QH880 UT WOS:A1995QH88000005 PM 7769606 ER PT J AU FLANDERS, KC HOLDER, MG WINOKUR, TS AF FLANDERS, KC HOLDER, MG WINOKUR, TS TI AUTOINDUCTION OF MESSENGER-RNA AND PROTEIN EXPRESSION FOR TRANSFORMING GROWTH FACTOR-BETA-S IN CULTURED CARDIAC-CELLS SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE GROWTH FACTORS; TRANSFORMING GROWTH FACTOR-BETA; AUTOINDUCTION; CARDIOPROTECTION; CULTURED CARDIOMYOCYTES; CULTURED CARDIAC FIBROBLASTS ID TGF-BETA; MESSENGER-RNA; ADULT TISSUES; FACTOR-BETA-1; TRANSCRIPTION; FIBROBLASTS; PRECURSOR; SEQUENCE; EMBRYOS; CLONING AB Although transforming growth factor-beta s (TGF-beta s) are expressed widely in both adult and embryonic rat heart, both mRNA and protein expression increase following ischemic injury, Furthermore, exogenous administration of TGF-beta decreases cardiac damage following ischemia-reperfusion in rats, We have found that treatment of primary cultures of neonatal rat cardiomyocytes or cardiac fibroblasts with TGF-beta 1, 2, or 3 results in increased expression of TGF-beta 1, 2, and 3 mRNA, TGF-beta 2 was generally the least effective isoform in inducing TGF-beta expression. In cardiac fibroblasts mRNA expression of all TGF-beta s increased 2-3-fold following 1 h of treatment and decreased to control levels by 8 h which was accompanied by a 2.5- and 2.3-fold increase in TGF-beta 1 and 2 protein secretion, respectively By 48 h of treatment mRNA levels for TGF-beta s 2 and 3 were less than 10% of control levels, In cardiomyocytes two-five-fold increases in mRNA levels were observed following 1-24 h of TGF-beta 1 treatment, but TGF-beta 1 and 3 mRNA levels returned to control values by 48 h while TGF-beta 2 mRNA expression remained elevated, TGF-beta 1 and 2 protein secreted by the cardiac myocytes was increased 2.9- and 1.7-fold, respectively. Autoinduction of TGF-beta s may play a beneficial role in cardiac wound healing by sustaining transient increases in TGF-beta levels from either endogenous synthesis or exogenous application. RP FLANDERS, KC (reprint author), NCI, CHEMOPREVENT LAB, BLDG 41 ROOM C-629, BETHESDA, MD 20892 USA. NR 33 TC 38 Z9 40 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD FEB PY 1995 VL 27 IS 2 BP 805 EP 812 DI 10.1016/0022-2828(95)90087-X PG 8 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA QN008 UT WOS:A1995QN00800009 PM 7776387 ER PT J AU PARK, BH FISHBURN, CS CARMON, S ACCILI, D FUCHS, S AF PARK, BH FISHBURN, CS CARMON, S ACCILI, D FUCHS, S TI STRUCTURAL ORGANIZATION OF THE MURINE D-3 DOPAMINE-RECEPTOR GENE SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE MURINE D-3 RECEPTOR; D-2 DOPAMINE RECEPTOR; ANTIPSYCHOTIC DRUGS; DOPAMINE; NEUROPATHOLOGICAL DISEASE; NEUROTRANSMISSION; RAT D-3 RECEPTOR ID DIFFERENTIAL EXPRESSION; MOLECULAR-CLONING; RAT; D1; D3; SEQUENCE; AFFINITY; TARGET; CDNA AB We have cloned the gene encoding the murine D-3 dopamine receptor and have analyzed its intron-exon structural organization, to gain a better understanding of the detailed architecture of the D-2 dopamine receptor genes. Restriction and sequence analysis reveal the presence of six introns, in contrast to the five introns previously reported for the rat D-3 receptor. The extra intron is located in the receptor's putative third cytoplasmic loop and generates an intron-exon organization directly analogous to that found in the D-2 receptor gene. In addition, we have sequenced the 5' and 3' nontranslated sequences flanking the coding region and have identified a putative poly(A) adenylation signal. These sequences are found to have a far lower homology with the corresponding rat nontranslated sequences than is found for the D-2 receptor, suggesting that the control of D-3 receptor expression may vary more between species than the control of D-2 receptor expression. C1 WEIZMANN INST SCI,DEPT CHEM IMMUNOL,IL-76100 REHOVOT,ISRAEL. NIDDK,DIABET BRANCH,BETHESDA,MD. NR 27 TC 26 Z9 26 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD FEB PY 1995 VL 64 IS 2 BP 482 EP 486 PG 5 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA QD027 UT WOS:A1995QD02700002 PM 7830039 ER PT J AU SUH, HW HUDSON, PM HONG, JS AF SUH, HW HUDSON, PM HONG, JS TI EXPRESSION OF THE PROENKEPHALIN A GENE AND [MET(5)]-ENKEPHALIN SECRETION INDUCED BY ARACHIDONIC-ACID IN BOVINE ADRENAL-MEDULLARY CHROMAFFIN CELLS - INVOLVEMENT OF 2ND MESSENGERS SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE ADRENAL MEDULLA; CALCIUM CHANNELS; CALMODULIN; GENE REGULATION; OPIOID PEPTIDES; PROTEIN KINASE C; 2ND MESSENGERS ID CATECHOLAMINE RELEASE; PHOSPHOINOSITIDE METABOLISM; A GENE; ENKEPHALIN BIOSYNTHESIS; CALMODULIN INHIBITORS; CALCIUM CHANNELS; CA-2+ CHANNELS; STIMULATION; RNA; PROSTAGLANDIN-E2 AB We have previously reported that arachidonic acid (AA) increases the long-term secretion of [Met(5)]-enkephalin (ME) and the expression of proenkephalin A (proENK) mRNA in bovine adrenal medullary chromaffin (BAMC) cells. To characterize the underlying signal transductional mechanisms for the AA-induced responses, the interactions of AA with several second messenger systems were studied. Long-term (24-h) treatment with AA (100 mu M) increased both the secretion of ME and the expression of proENK mRNA. Pretreatment of BAMC cells with nimodipine (1 mu M), but not with omega-conotoxin GVIA (1 mu M), inhibited the secretion of ME and the expression of proENK mRNA induced by AA. Calmidazolium (1 mu M), a calmodulin antagonist, also significantly inhibited AA-induced responses. However, a protein kinase C (PKC) inhibitor, sphingosine (36 mu M), was ineffective in blocking AA-induced responses. In addition, the down-regulation of PKC by phorbol 12-myristate 13-acetate (0.1 mu M) for 48 h did not inhibit the AA-induced responses. Forskolin (5 mu M), an adenyl cyclase activator, alone increased the secretion of ME as well as proENK mRNA levels and, when coincubated with AA, showed an additive effect on the secretion of ME and the levels of proENK mRNA. The results suggest that the Ca2+/calmodulin pathway, but not the protein kinase A or PKC pathway, is partially involved in mediating the AA-induced increases of the long-term secretion of ME and the levels of proENK mRNA. C1 NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,NEUROPHARMACOL SECT,RES TRIANGLE PK,NC 27709. RP SUH, HW (reprint author), HALLYM UNIV,COLL MED,DEPT PHARMACOL,1 OKCHUN DONG,CHUNCHON 200702,SOUTH KOREA. NR 36 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD FEB PY 1995 VL 64 IS 2 BP 608 EP 613 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA QD027 UT WOS:A1995QD02700017 PM 7830054 ER PT J AU WHITE, BH KLEIN, DC AF WHITE, BH KLEIN, DC TI STIMULATION OF CYCLIC-GMP ACCUMULATION BY SODIUM-NITROPRUSSIDE IS POTENTIATED VIA A G(S) MECHANISM IN INTACT PINEALOCYTES SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE CYCLIC GMP; PINEAL; NITROPRUSSIDE; AND GATES; G(S)ALPHA; NITRIC OXIDE; CHOLERA TOXIN ID INTESTINAL-PEPTIDE STIMULATION; CYTOSOLIC GUANYLATE-CYCLASE; PROTEIN KINASE-C; RAT PINEALOCYTES; ADENYLATE-CYCLASE; NITRIC-OXIDE; GUANOSINE 3',5'-MONOPHOSPHATE; ADRENERGIC-STIMULATION; N-ACETYLTRANSFERASE; ALPHA-SUBUNIT AB Cyclic GMP accumulation in pinealocytes is elevated >100-fold by norepinephrine (NE) through a mechanism involving conjoint activation of alpha(1)-and beta(1)-adrenergic receptors. Little or no stimulation occurs if either alpha(1)- or beta(1)-adrenergic receptors alone are activated. It appears that alpha(1)-adrenergic effects are mediated by Ca2+ acting in part through nitric oxide (NO), and beta(1)-adrenergic effects are mediated by G(s). In the study presented here we investigated effects of adrenergic agonists or related postreceptor-active agents on stimulation of pineal cyclic GMP accumulation by the NO generator sodium nitroprusside (NP). The cyclic GMP response to NP (1 mM) was potentiated by NE and isoproterenol (ISO) but not by phenylephrine, indicating that activation of beta(1)-adrenergic receptors potentiates the effects of NP. Similarly, vasoactive intestinal peptide (VIP), cholera toxin (CTX), and forskolin, all of which are known to mimic the effects of ISO in this system, also potentiated the effects of NP. In contrast, neither dibutyryl cyclic AMP nor agents that elevate intracellular Ca2+ levels caused marked potentiation of the effects of NP on pineal cyclic GMP. Depletion (90%) of G(s) alpha by 21-h treatment with CTX reduced beta-adrenergic potentiation of NP. These findings indicate that beta-adrenergic agonists and VIP potentiate the effects of NP through a mechanism involving G(s). The molecular basis of this action may be an increase in guanylyl cyclase responsiveness to NO. C1 NICHHD,DEV NEUROBIOL LAB,NEUROENDOCRINOL SECT,BETHESDA,MD 20892. NR 34 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD FEB PY 1995 VL 64 IS 2 BP 711 EP 717 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA QD027 UT WOS:A1995QD02700029 PM 7830064 ER PT J AU FAN, P AF FAN, P TI CANNABINOID AGONISTS INHIBIT THE ACTIVATION OF 5-HT3 RECEPTORS IN RAT NODOSE GANGLION NEURONS SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Note ID ANANDAMIDE; BRAIN; CELLS; PHARMACOLOGY; CURRENTS; BINDS AB 1. Effects of cannabinoid agonists on the serotonin (5-HT)(3) receptor-mediated current were investigated in rat nodose ganglion neurons. Anandamide. Win 55212-2, and CP55940 inhibitid the 5-HT-induced current in a concentration dependent manner. IC50 values were 190, 310, and 94 nM for anandamide. Win 55212-2, and CP55940, respectively, and 1.6 mu M for the nonpsychoactive enantiomer CP56667. This inhibition was slowly developing, noncompetitive, not dependent on membrane potential, and not affected by adenosine 3'.5'-cyclic monophosphate(cAMP) analogues. guanosine-5'-O-(2-thiodiphosphate) (GDP-beta-S), and opioid receptor antagonist naltrexone. These data suggest that 5-HT3 receptor ion-channel is a site acted upon by cannabinoid agonists in the nervous system, and the action of cannabinoid agonists on 5-HT3 receptors may be a possible mechanism for some of the behavioral effects of cannabinoids, such as antiemesis and analgesia. RP FAN, P (reprint author), NIAAA,CELLULAR & MOLEC NEUROBIOL LAB,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 16 TC 118 Z9 124 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD FEB PY 1995 VL 73 IS 2 BP 907 EP 910 PG 4 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA QU215 UT WOS:A1995QU21500044 PM 7760148 ER PT J AU MCBAIN, CJ AF MCBAIN, CJ TI HIPPOCAMPAL INHIBITORY NEURON ACTIVITY IN THE ELEVATED POTASSIUM MODEL OF EPILEPSY SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Note ID GUINEA-PIG HIPPOCAMPUS; PYRAMIDAL CELLS; EPILEPTIFORM ACTIVITY; ORIENS-ALVEUS; INVITRO; CA3; RECEPTOR; SLICES; MEMBRANE; INTERNEURONS AB 1. Whole cell patch-clamp recordings were made from CA1 stratum oriens inhibitory neurons of rat hippocampal slices in vitro to determine their contribution to the epileptiform attivity elicited by elevating the extracellular potassium ion concentration ([K+](o)) from 3.5 to 8.5 mM. 2. Under current-clamp conditions. spontaneous action potential activity in inhibitory neurons normally occurs in a sustained repetitive firing mode paced by nonsynaptic. intrinsic mechanisms, On elevation of [K+](o) to 8.5 mM the pattern of activity is altered such that clusters of action potentials occur interrupted bq periods of silence without an appreciable afterhyperpolarization (AHP). In addition, elevation of [K+](o) caused a large reduction in the action potential AHP amplitude and duration concomitant with a 20-mV shift in the reversal potential of the AHP. 3. In voltage clamp a small persistent inward current was observed after the introduction of elevated potassium concomitant with an increase in the frequency of spontaneous excitatory postsynaptic currents (EPSCs) in all interneurons studied. After a short period of time (similar to 1 min) temporal summation of synchronously occurring EPSCs contributed a periodic inward current (PIC, 10-40 pA, 0.8 Hz) that persisted for the duration of the [K+](o) elevation. Analysis of the charge transfer associated with the PIC suggests that they comprise the temporal summation of similar to 35 EPSCs. This PIC was synchronous with the extracellular field potential recorded from the CA1 pyramidal neuron layer. 4. The PIC was responsible for the clustering of action potential activity because blockade of EPSC activity by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) abolished PICs and reverted action potential activity to single sustained firing, despite the continued application bf 8,5 mM [K+](o). Antagonists of N-methyl-D-aspartate receptors were without effect on either the PICs or the action potential activity. 5. Addition of the metabotropic glutamate receptor (mGluR) antagonist (+)-2-methyl-4-carboxyphenylglycine (MCPG) reversibly abolished the PIC without affecting the increase in EPSC frequency. 6. Recordings from CA3 pyramidal neurons in 8.5 mM [K+](o) demonstrated that interictal activity occurred at a frequency identical to the PICs observed in interneurons. Interictal activity in CA3 pyramidal neurons was attenuated but never abolished by MCPG, suggesting a role for mGluR receptors in the maintenance of interictal activity in area CA3. 7. Flurries of synchronous inhibitory postsynaptic currents (IPSCs) were observed on a small number of CA1 pyramidal neurons on elevation of [K+](o), consistent with these neurons being the synaptic target of stratum oriens/alveus interneurons. Unexpectedly, a rundown of this IPSC activity was observed during the transition to CA1 pyramidal neuron epileptiform activity. 8. In CA1 pyramidal neurons, current-voltage relationships measured at the peak response to GABA were identical in both normal or elevated [K+](o). However, subsequent current-voltage relationships determined during the Fade of the GABA response revealed a positive shift in the reversal potential in both control and 8.5 mM [K+](o) conditions. The mechanism for this positive shift in reversal potential is at present unknown but may occur due to the intracellular accumulation of Cl- after sustained GABA receptor activation. 9. These experiments suggest that the ongoing intrinsic action potential activity of the CA1 interneuron population is ''overridden'' during electrographic activity resulting from [K+](o) elevation. The resulting activity is paced by interictal events occurring in the CA3 pyramidal neuron population. A role for mGluRs in the interictal activity of the CA3 pyramidal neuron population is also described, After the establishment of epileptiform activity, synaptic inhibition onto CA1 pyramidal neurons is severly attenuated. This results not From the [K+](o) elevation per se but possibly from an activity-dependent Cl- redistribution across the CA1 pyramidal neurons after sustained IPSC activity. RP MCBAIN, CJ (reprint author), NICHHD,CELLULAR & MOLEC NEUROPHYSIOL LAB,CELLULAR & SYNAPT PHYSIOL UNIT,RM 5A72,BLDG 49,BETHESDA,MD 20892, USA. NR 35 TC 19 Z9 19 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD FEB PY 1995 VL 73 IS 2 BP 2853 EP 2863 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA QU215 UT WOS:A1995QU21500047 PM 7760109 ER PT J AU LIESI, P HAGER, G DODT, HU SEPPALA, I ZIEGLGANSBERGER, W AF LIESI, P HAGER, G DODT, HU SEPPALA, I ZIEGLGANSBERGER, W TI DOMAIN-SPECIFIC ANTIBODIES AGAINST THE B2 CHAIN OF LAMININ INHIBIT NEURONAL MIGRATION IN THE NEONATAL RAT CEREBELLUM SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE B2 CHAIN; LAMININ; NEURONAL MIGRATION; RAT CEREBELLUM ID OUTGROWTH-PROMOTING DOMAIN; PROTEIN-KINASE-C; NEURITE OUTGROWTH; CELL-MIGRATION; CHICK-EMBRYO; EXTRACELLULAR-MATRIX; ADHESION MOLECULES; NUCLEAR-MOVEMENT; MOUSE CEREBELLUM; NEUROBLASTS AB Although the spatial and temporal patterns of neuronal migration have been analyzed in great detail, little direct evidence is available as to what extracellular matrix molecules are involved. Because there is indirect evidence implicating the extracellular matrix protein laminin in neuronal migration, we investigated the effects of antibodies against a synthetic peptide derived from a neurite outgrowth domain of the B2 chain of laminin on neuronal migration in living cerebellar slices. We show by using infrared video microscopy that divalent Fab(2) fragments of these antibodies inhibit granule neuronal movement in living slices of (P8) rat cerebellum. This inhibition of neuronal movement manifests itself by cessation of both radial and horizontal translocations of nuclei inside the granule neuronal processes. Fab(2) fragments of antibodies against the intact (native) laminin molecule or Fab(2) fragments from the preimmune serum do not affect nuclear translocation. Immunocytochemistry shows binding of the divalent Fab(2) fragments of the B2 chain-specific antibodies to the Purkinje and Bergmann glial cell areas, and as punctate deposits in between the cells of the external granule cell layer. Native laminin antibodies bind to the basement membranes, and binding of the Fab, fragments from the preimmune sera cannot be demonstrated. These results indicate that neuronal migration in the postnatal rat cerebellum in vivo involves nuclear translocation that can be inhibited by antibodies against a neurite outgrowth domain of the B2 chain of laminin. Thus, migration of cerebellar granule neurons may depend on the interaction between a neurite outgrowth domain of the B2 chain of laminin and neuronal cytoskeleton involved in nuclear movement. (C) 1995 Wiley-Liss, Inc. C1 UNIV HELSINKI,DEPT ANAT,HELSINKI,FINLAND. UNIV HELSINKI,DEPT SEROBACTERIOL,HELSINKI,FINLAND. MAX PLANCK INST PSYCHIAT,INST CLIN,DEPT CLIN NEUROPHARMACOL,W-8000 MUNICH,GERMANY. RP LIESI, P (reprint author), NIAAA,MOLEC & CELLULAR NEUROBIOL LAB,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 50 TC 56 Z9 56 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD FEB 1 PY 1995 VL 40 IS 2 BP 199 EP 206 DI 10.1002/jnr.490400208 PG 8 WC Neurosciences SC Neurosciences & Neurology GA QE379 UT WOS:A1995QE37900007 PM 7745613 ER PT J AU HAGER, G DODT, HU ZIEGLGANSBERGER, W LIESI, P AF HAGER, G DODT, HU ZIEGLGANSBERGER, W LIESI, P TI NOVEL FORMS OF NEURONAL MIGRATION IN THE RAT CEREBELLUM SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE CEREBELLUM; INFRARED VIDEO MICROSCOPY; NEURONAL MIGRATION; NUCLEAR MOVEMENT ID DEVELOPING CEREBRAL-CORTEX; GRANULE CELL-MIGRATION; POSTNATAL-DEVELOPMENT; CHICK-EMBRYO; INVITRO; DIFFERENTIATION; LAMININ; GANGLION; NEUROBLASTS; ANTIBODIES AB Infrared video microscopy of neonatal rat cerebellum (P0-P14) was used to directly visualize migrating granule neurons in relation to other cerebellar cells in a brain slice for up to 24 hr. Initially (P0-P5), granule neurons move along radial migration pathways of other neuronal fibers. These pathways are probably established by the bipolar granule neurons that attach to the external basement membrane via one process and extend another process toward the Purkinje cell layer. At P5-P8, a substantial number of granule neurons move horizontally and extend long parallel fibers. Both radially and horizontally migrating granule neurons move by nuclear translocation inside their preformed processes with a speed that varies between 6 and 120 mu m/hr. In P10-P12 animals, the horizontally oriented granule neurons start to migrate radially. They move into the internal granule cell layer either along the radial pathways of other neuronal fibers or in contact with the matured glial processes. The radial neuronal migration pathways disappear by P14 whereas the glial cell processes are maintained and reach the basal lamina. These results describe novel radial and horizontal modes of neuronal migration that proceed independently of the physical glial guidance. (C) 1995 Wiley-Liss, Inc. C1 NIAAA,MOLEC & CELLULAR NEUROBIOL LAB,ROCKVILLE,MD 20852. MAX PLANCK INST PSYCHIAT,INST CLIN,DEPT CLIN NEUROPHARMACOL,W-8000 MUNICH,GERMANY. UNIV HELSINKI,DEPT ANAT,NEUROBIOL LAB,HELSINKI,FINLAND. NR 42 TC 49 Z9 49 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD FEB 1 PY 1995 VL 40 IS 2 BP 207 EP 219 DI 10.1002/jnr.490400209 PG 13 WC Neurosciences SC Neurosciences & Neurology GA QE379 UT WOS:A1995QE37900008 PM 7745614 ER PT J AU ZHAO, B SISODIA, SS KUSIAK, JW AF ZHAO, B SISODIA, SS KUSIAK, JW TI ALTERED PROCESSING OF A MUTANT AMYLOID PRECURSOR PROTEIN IN NEURONAL AND ENDOTHELIAL-CELLS SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Note DE ALZHEIMER DISEASE; AMYLOIDOGENESIS; AP PEPTIDE; LYSOSOMES ID ALZHEIMERS-DISEASE; MESSENGER-RNA; NEUROFIBRILLARY TANGLES; BETA-PROTEIN; A4 PRECURSOR; EXPRESSION; NEUROTOXICITY; BRAIN; IDENTIFICATION; DERIVATIVES AB Altered proteolysis of the amyloid precursor protein (APP) may play an important role in Alzheimer disease (AD). To better understand the role of mutant APP in the pathogenesis of the disease, we stably overexpressed the mutant APP717F approximately twofold vs. the endogenous wild-type gene in several cell types. The processing of APP was examined by Western blot analysis and immunoprecipitation. We observed distinctive patterns of APP metabolites among various cell lines. Neuronal and endothelial cells expressing mutant APP717F generated higher levels of large, potentially amyloidogenic carboxyl terminal fragments, which were enhanced upon treatment of the cells with leupeptin. These results suggest that mutations in the APP gene shift the protein processing towards the amyloidogenic pathway in neuronal and endothelial cells possibly involving the endosomal-lysosomal system. (C) 1995 Wiley-Liss, Inc. C1 JOHNS HOPKINS UNIV,DEPT PATHOL,BALTIMORE,MD. RP ZHAO, B (reprint author), NIA,GERONTOL RES CTR,LBC,MOLEC NEUROBIOL UNIT,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 38 TC 16 Z9 18 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD FEB 1 PY 1995 VL 40 IS 2 BP 261 EP 268 DI 10.1002/jnr.490400215 PG 8 WC Neurosciences SC Neurosciences & Neurology GA QE379 UT WOS:A1995QE37900014 PM 7745619 ER PT J AU BARTLETT, ML BACHARACH, SL VOIPIOPULKKI, LM DILSIZIAN, V AF BARTLETT, ML BACHARACH, SL VOIPIOPULKKI, LM DILSIZIAN, V TI ARTIFACTUAL INHOMOGENEITIES IN MYOCARDIAL PET AND SPECT SCANS IN NORMAL SUBJECTS SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE HEART; EMISSION COMPUTED TOMOGRAPHY; ARTIFACTS; PARTIAL VOLUME EFFECT ID EMISSION COMPUTED-TOMOGRAPHY; WALL MOTION; VOLUME; QUANTIFICATION AB It has been well established that PET and SPECT scans of human myocardium are subject to partial volume related effects, which can cause artifactual regional variations in activity around the myocardium. This study investigated the sources and magnitude of such artifactual inhomogeneity in subjects with normal cardiac function. Method: Using multi-slice, gated MRI scans from 9 normal subjects, we examined separately the influences on measured activity of wall motion, axial resolution and the relationship between wall thickness and in-plane resolution. Results: Two patterns of artifactual inhomogeneity were found: a depression in activity at the antero-apex and an elevation in activity in the free wall compared with the septum. Thus, in ungated PET images the true apical/septal ratio was artifactually reduced by a factor of 0.89 (0.92 for SPECT), while the true free wall/septal ratio was enhanced by a factor of 1.12 (1.19 for SPECT). Gating improved uniformity in end-systolic (ES) images but degraded uniformity in end-diastolic (ED) images. With gating, the true PET apical/septal ratio was artifactually reduced by only 0.97 at ES, and 0.82 at ED. Similar behavior was found for SPECT. Improvements in axial resolution were found to have little effect on artifactual variations. Conclusion: We find that the relationship between in-plane resolution and wall thickness, but not axial resolution, is of prime importance in determining the degree of artifactual inhomogeneity in ungated scans of normal human myocardium. Gating improved ES but degraded ED homogeneity. C1 UNIV TURKU,DEPT MED,TURKU,FINLAND. RP BARTLETT, ML (reprint author), NIH,DEPT NUCL MED,BLDG 10,ROOM 1C401,BETHESDA,MD 20892, USA. NR 15 TC 39 Z9 39 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD FEB PY 1995 VL 36 IS 2 BP 188 EP 195 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QE714 UT WOS:A1995QE71400010 PM 7830111 ER PT J AU BLAIR, A ZAHM, SH AF BLAIR, A ZAHM, SH TI OVERINTERPRETATION OF SMALL NUMBERS IN THE DOW 2,4-D COHORT STUDY SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Letter RP BLAIR, A (reprint author), NCI,OCCUPAT STUDIES SECT,BETHESDA,MD 20892, USA. NR 1 TC 4 Z9 4 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD FEB PY 1995 VL 37 IS 2 BP 126 EP 126 DI 10.1097/00043764-199502000-00004 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QH775 UT WOS:A1995QH77500004 PM 7655952 ER PT J AU MACDONALD, N ALEXANDER, HR BRUERA, E AF MACDONALD, N ALEXANDER, HR BRUERA, E TI CACHEXIA-ANOREXIA-ASTHENIA SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE CACHEXIA; ANOREXIA; RESEARCH WORKSHOP ID TUMOR NECROSIS FACTOR; FACTOR-ALPHA CACHECTIN; CANCER CACHEXIA; INTERLEUKIN-1 AB The National Cancer Institute (Canada) sponsored a workshop on symptom control in Banff, Alberta, in October 1933. This article reports on the workshop recommendations for research on one symptom complex, the cachexia-anorexia-asthenia syndrome. In addition to encouraging study generation the recommendations provide a baseline for assessing the scope and strength of future Canadian research initiatives on cachexia-anorexia-asthenia. C1 EDMONTON GEN HOSP,EDMONTON,AB,CANADA. NCI,SURG BRANCH,BETHESDA,MD 20892. RP MACDONALD, N (reprint author), CLIN RES INST MONTREAL,CTR BIOETH,110 PINE AVE W,MONTREAL,PQ H2Q 1R7,CANADA. NR 13 TC 17 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD FEB PY 1995 VL 10 IS 2 BP 151 EP 155 DI 10.1016/0885-3924(94)00077-X PG 5 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA QN863 UT WOS:A1995QN86300011 PM 7730686 ER PT J AU ZIERDT, CH ZIERDT, WS NAGY, B AF ZIERDT, CH ZIERDT, WS NAGY, B TI ENZYME-LINKED-IMMUNOSORBENT-ASSAY FOR DETECTION OF SERUM ANTIBODY TO BLASTOCYSTIS-HOMINIS IN SYMPTOMATIC INFECTIONS SO JOURNAL OF PARASITOLOGY LA English DT Note ID DISEASE AB An enzyme-linked immunosorbent assay was devised in order to search for antibodies against Blastocystis hominis in infected humans. Reaction proteins were obtained from washed, axenic B. hominis cells, as sonicate. Sonicate was diluted to provide 17 and 34 mu g of protein per well. Dilutions of patients' sera were applied, followed by phosphatase-conjugated goat anti-human serum and phosphatase substrate. Color was measured at 405 mu m wavelength. Immunoglobulin G antibodies to high titers were found. Of 30 sera tested from 28 patients, 3 were negative at the 1/50 threshold dilution, 8 were positive at 1/50, 3 at 1/100, 2 at 1/200, 3 at 1/400, 6 at 1/800, and 5 at 1/1,600. Normal sera (42 blood bank sera) were all negative at 1/50. Each serum was subjected to multiple testing. Duplicate tests were included for each run, and runs were made from 4 to 6 for each serum. Blastocystis hominis is increasingly recognized to be a cause of human enteric disease, with symptoms often like those in giardiasis. Demonstration of strong antibody response is consistent with this view. RP ZIERDT, CH (reprint author), NIH,CTR CLIN,DEPT CLIN PATHOL,MICROBIOL SERV,BETHESDA,MD 20892, USA. RI Nagy, Balint/F-6943-2012 NR 13 TC 27 Z9 31 U1 0 U2 0 PU AMER SOC PARASITOLOGISTS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 SN 0022-3395 J9 J PARASITOL JI J. Parasitol. PD FEB PY 1995 VL 81 IS 1 BP 127 EP 129 DI 10.2307/3284026 PG 3 WC Parasitology SC Parasitology GA QH938 UT WOS:A1995QH93800028 PM 7876972 ER PT J AU SIGELMAN, CK MUKAI, T WOODS, T ALFELD, C AF SIGELMAN, CK MUKAI, T WOODS, T ALFELD, C TI PARENTS CONTRIBUTIONS TO CHILDRENS KNOWLEDGE AND ATTITUDES REGARDING AIDS - ANOTHER LOOK SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Eastern-Psychological-Association CY APR 14-17, 1994 CL PROVIDENCE, RI SP E Psychol Assoc DE AIDS; PARENTS; CHILDREN; SOCIALIZATION; KNOWLEDGE; ATTITUDES ID FAMILY COMMUNICATION; GENERAL-POPULATION; PERCEPTIONS; ADOLESCENTS; AWARENESS; STUDENTS; BEHAVIOR AB Attempted to determine, using a sample of students in Grades 3, 5, and 7, whether parent-child communication about AIDS and parent knowledge of AIDS predict children's knowledge, social attitudes, and worry regarding AIDS, partially replicating tests by Sigelman, Derenowski, Mullaney, and Siders (1993) of main effects, interaction, and potentiation models of parent-child socialization. Most parents had talked to their children about AIDS but many were susceptible to myths about HIV transmission. Child age was the strongest predictor of accurate knowledge and positive attitudes, but gender, ethnicity, and parent education also made modest contributions. Consistent with the potentiation model, parent knowledge of common transmission myths predicted child knowledge of those same myths (and willingness to interact with individuals who have AIDS as well) only when parent-child communication about AIDS was relatively extensive (and only when child rather than parent reported it). Findings suggest that both the quantity and quality of parental messages must be considered by socialization researchers but that parents may not be the primary socializers of knowledge and attitudes regarding AIDS and other health issues. C1 NIMH,BETHESDA,MD 20892. UNIV MIAMI,CORAL GABLES,FL 33124. UNIV MICHIGAN,ANN ARBOR,MI 48109. RP SIGELMAN, CK (reprint author), GEORGE WASHINGTON UNIV,DEPT PSYCHOL,WASHINGTON,DC 20052, USA. FU NICHD NIH HHS [HD27274] NR 31 TC 21 Z9 21 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0146-8693 J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD FEB PY 1995 VL 20 IS 1 BP 61 EP 77 DI 10.1093/jpepsy/20.1.61 PG 17 WC Psychology, Developmental SC Psychology GA QG792 UT WOS:A1995QG79200007 PM 7891241 ER PT J AU ROSS, JL FEUILLAN, P LONG, LM KOWAL, K KUSHNER, H CUTLER, GB AF ROSS, JL FEUILLAN, P LONG, LM KOWAL, K KUSHNER, H CUTLER, GB TI LIPID ABNORMALITIES IN TURNER SYNDROME SO JOURNAL OF PEDIATRICS LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; PLASMA; INSULIN; CHOLESTEROL; ADOLESCENTS; METABOLISM; CHILDREN; HORMONE AB Turner syndrome is associated with insulin resistance, increased incidence of type II diabetes, and hypertension, all of which are cardiovascular risk factors. The purpose of this study was to evaluate the lipid profile of girls with untreated Turner syndrome, (aged 5 to 14 years; 68% 45,XO) and age-matched, normal girls, A total of 137 girls with Turner syndrome and 70 normal girls had lipid profile measurements, including cholesterol, high-density lipoprotein cholesterol, and triglycerides. Older girls with Turner syndrome (>11.0 years) had increased cholesterol levels (p <0.01), compared with control values (190 +/- 38 vs 165 +/- 26 mg/dl). Cholesterol levels were elevated in older subjects with Turner syndrome versus normal subjects, after adjustment for age, karyotype, and body mass index z score effects (p = 0.01), In the subjects with Turner syndrome but not the normal subjects, serum cholesterol values correlated with age, weight, and body mass index z score (p <0.02). We conclude that adolescent girls with untreated Turner syndrome have significantly increased cholesterol levels, independent of age, body mass index z score, or karyotype, and that these precede any treatment with exogenous estrogen or growth hormone. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. HAHNEMANN UNIV, DEPT STAT, PHILADELPHIA, PA 19102 USA. RP ROSS, JL (reprint author), THOMAS JEFFERSON UNIV, DEPT PEDIAT, 1025 WALNUT ST, PHILADELPHIA, PA 19107 USA. NR 16 TC 48 Z9 50 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD FEB PY 1995 VL 126 IS 2 BP 242 EP 245 DI 10.1016/S0022-3476(95)70551-1 PG 4 WC Pediatrics SC Pediatrics GA QG219 UT WOS:A1995QG21900012 PM 7844670 ER PT J AU COSTA, PT MCCRAE, RR AF COSTA, PT MCCRAE, RR TI DOMAINS AND FACETS - HIERARCHICAL PERSONALITY-ASSESSMENT USING THE REVISED NEO PERSONALITY-INVENTORY SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article; Proceedings Paper CT Convention of the American-Psychological-Society CY JUN, 1992 CL SAN DIEGO, CA SP AMER PSYCHOL SOC ID CALIFORNIA PSYCHOLOGICAL INVENTORY; 5-FACTOR MODEL; TRAITS; CIRCUMPLEX; SCALES; DIMENSIONS; EXPERIENCE; OPENNESS; BIG-5; LEVEL AB Personality traits are organized hierarchically, with narrow, specific traits combining to define broad, global factors. The Revised NEO Personality Inventory (NEO-PI-R; Costa & McCrae, 1992c) assesses personality at both levels, with six specific facet scales in each of five broad domains. This article describes conceptual issues in specifying facets of a domain and reports evidence on the validity of NEO-PI-R facet scales. Facet analysis-the interpretation of a scale in terms of the specific facets with which it correlates-is illustrated using alternative measures of the five-factor model and occupational scales. Finally, the hierarchical interpretation of personality profiles is discussed. Interpretation on the domain level yields a rapid understanding of the individual; interpretation of specific facet scales gives a more detailed assessment. RP COSTA, PT (reprint author), NIA,GERONTOL RES CTR,PERSONAL & COGNIT LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 64 TC 592 Z9 599 U1 24 U2 182 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD FEB PY 1995 VL 64 IS 1 BP 21 EP 50 DI 10.1207/s15327752jpa6401_2 PG 30 WC Psychology, Clinical; Psychology, Social SC Psychology GA QE826 UT WOS:A1995QE82600002 PM 16367732 ER PT J AU CARPENTER, TO GERLOCZY, A PITHA, J AF CARPENTER, TO GERLOCZY, A PITHA, J TI SAFETY OF PARENTERAL HYDROXYPROPYL-BETA-CYCLODEXTRIN SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID HYPERVITAMINOSIS; DISSOLUTION; TOXICITY; RATS AB Post-treatment data were collected on a patient who received intravenous hydroxypropyl beta-cyclodextrin in a dose of 1.5 g/kg in 1985. Although no untoward effects were observed in this patient, rarely occurring agitation and pulmonary edema have been noted after injections into rabbits and dogs, respectively. These complications are analyzed here on the basis of symptoms and on the effects of hydroxypropyl beta-cyclodextrin on the biochemistry of a representative lipid, cholesterol, which were studied in rats. It is hypothesized that these untoward effects of parenteral hydroxypropyl beta-cyclodextrin are due to complex formation, with lipid mediators of pathological responses, of which prostaglandins are one example. These mediators normally have brief and localized functions; if hydroxypropyl beta-cyclodextrin happens to be injected when these mediator systems are activated, their influence and the responses of the organism may be increased. C1 CYCLOLAB,BUDAPEST,HUNGARY. NIA,GRC,BALTIMORE,MD 21224. RP CARPENTER, TO (reprint author), YALE UNIV,SCH MED,DEPT PEDIAT,NEW HAVEN,CT 06510, USA. NR 22 TC 35 Z9 38 U1 1 U2 4 PU AMER PHARMACEUTICAL ASSN PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD FEB PY 1995 VL 84 IS 2 BP 222 EP 225 DI 10.1002/jps.2600840220 PG 4 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA QF318 UT WOS:A1995QF31800019 PM 7738806 ER PT J AU QUEZADO, ZMN NATANSON, C BANKS, SM ALLING, DW KOEV, CA DANNER, RL ELIN, RJ HOSSEINI, JM PARKER, TS LEVINE, DM RUBIN, AL HOFFMAN, WD AF QUEZADO, ZMN NATANSON, C BANKS, SM ALLING, DW KOEV, CA DANNER, RL ELIN, RJ HOSSEINI, JM PARKER, TS LEVINE, DM RUBIN, AL HOFFMAN, WD TI THERAPEUTIC TRIAL OF RECONSTITUTED HUMAN HIGH-DENSITY-LIPOPROTEIN IN A CANINE MODEL OF GRAM-NEGATIVE SEPTIC SHOCK SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID TUMOR-NECROSIS-FACTOR; APOLIPOPROTEIN-A-I; CARDIOVASCULAR DYSFUNCTION; INTRAVENOUS ENDOTOXIN; ESCHERICHIA-COLI; BINDING-PROTEIN; FACTOR RELEASE; LIPOPOLYSACCHARIDE; INHIBITION; COMPLEXES AB In a controlled, randomized trial, the authors investigated the effects of reconstituted human high-density lipoprotein (R-HDL) on survival, endotoxemia, cytokine production and pathophysiologic and metabolic events in an animal model of gramnegative septic shock. At 0.5, 8 and 16 hr after implantation of a clot infected with Escherichia coli, canines received intravenous R-HDL (n = 13), control lipid (n = 7) or human serum albumin (HSA, n = 7) divided into three doses (0.3, 0.1 and 0.1 g/kg, respectively) at an hourly rate of 0.1 g/kg. All animals were treated with antibiotics and fluids. Animals treated with R-HDL had lower levels of circulating endotoxin and tumor necrosis factor and a smaller decrease in white blood cell counts than did animals treated with lipids and HSA (all P < .05). The survival times of lipid- and HSA-treated animals were similar (P = .3) and were significantly greater than those of R-HDL-treated animals (P = .02). During the first 6 hr after clot implantation, R-HDL-treated animals had significantly greater abnormalities in liver function test findings compared with lipid- and HSA-treated animals (all P < .05). For the first 24 hr, R-HDL-treated animals had significant increases in HDL levels; however, there were no significant relationships between these levels and the constituents of HDL(apolipoprotein Al and phosphatidylcholine) or liver function abnormalities and survival times (all r < .2, P > .3). In normal animals, administration of R-HDL (in similar doses) caused transient elevation of liver enzymes; in animals given sterile clot i.p., R-HDL caused seizures. Thus, in septic and nonseptic animals, this preparation of R-HDL produced hepatic and neurologic toxicity. However, in septic animals, R-HDL also improved leukopenia and decreased endotoxemia and circulating levels of tumor necrosis factor. If the toxicities associated with R-HDL can be reduced, its antiendotoxin effects should be investigated for their potential benefits in live bacterial infections. C1 NIH, DEPT CLIN PATHOL, BETHESDA, MD 20892 USA. CORNELL UNIV, MED CTR, NEW YORK HOSP, ROGOSIN INST, NEW YORK, NY 10021 USA. RP QUEZADO, ZMN (reprint author), NIH, DEPT CRIT CARE MED, BLDG 10, ROOM 7D43, 10 CTR DR MSC 1662, BETHESDA, MD 20892 USA. RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 NR 45 TC 32 Z9 35 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 EI 1521-0103 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD FEB PY 1995 VL 272 IS 2 BP 604 EP 611 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QG057 UT WOS:A1995QG05700016 PM 7853173 ER PT J AU SCHINDLER, CW TELLA, SR PRADA, J GOLDBERG, SR AF SCHINDLER, CW TELLA, SR PRADA, J GOLDBERG, SR TI CALCIUM-CHANNEL BLOCKERS ANTAGONIZE SOME OF COCAINE CARDIOVASCULAR EFFECTS, BUT FAIL TO ALTER COCAINE BEHAVIORAL-EFFECTS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CONSCIOUS SQUIRREL-MONKEYS; DISCRIMINATIVE STIMULUS PROPERTIES; D-AMPHETAMINE; RAT-BRAIN; NIMODIPINE; MECHANISMS; SCHEDULES; REINFORCEMENT; BAY-K-8644; ISRADIPINE AB The effects of cocaine alone and in combination with the calcium channel blockers nimodipine, verapamil and diltiazem were determined for different groups of squirrel monkeys on cardiovascular function, schedule-controlled behavior and drug self-administration. Cocaine alone (0.3 mg/kg) produced increases in both blood pressure and heart rate. All three calcium channel blockers antagonized the presser effect, but were ineffective against the tachycardiac effect of cocaine. Nimodipine was the most potent agent in antagonizing the presser effect of cocaine. Response rates for monkeys responding on a second-order schedule of food presentation were increased by intermediate doses of cocaine (0.1-1.0 mg/kg) and were primarily decreased at a higher dose (3.0 mg/kg). Quarter-life values, an index of response patterning, were only decreased by cocaine. None of the calcium channel blockers altered cocaine's effects on either response rate or response patterning. In the self-administration experiments, the training dose of 56 mu g/kg cocaine maintained high rates of responding on a simple fixed-ratio schedule. As with schedule-controlled behavior, none of the calcium channel blockers altered cocaine self-administration even when administered before serf-administration sessions during 5 consecutive days. These results suggest that the calcium channel blockers may be useful in treating cardiovascular-retated complications after cocaine use, but they would not be effective as long-term treatment agents for cocaine abuse. C1 NIDA,ADDICT RES CTR,DIV INTRAMURAL RES,BEHAV PHARMACOL & GENET SECT,PRECLIN PHARMACOL LA,BALTIMORE,MD 21224. UNIV MARYLAND,DEPT PHARMACOL & EXPTL THERAPEUT,BALTIMORE,MD 21201. GEORGETOWN UNIV,SCH MED,DEPT PHARMACOL,WASHINGTON,DC. NR 48 TC 18 Z9 18 U1 1 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD FEB PY 1995 VL 272 IS 2 BP 791 EP 798 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QG057 UT WOS:A1995QG05700041 PM 7853196 ER PT J AU ORZI, F SUN, Y PETTIGREW, K SOKOLOFF, L SMITH, CB AF ORZI, F SUN, Y PETTIGREW, K SOKOLOFF, L SMITH, CB TI EFFECTS OF ACUTE AND DELAYED-EFFECTS OF PRIOR CHRONIC COCAINE ADMINISTRATION ON REGIONAL RATES OF CEREBRAL PROTEIN-SYNTHESIS IN RATS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID EXTRACELLULAR DOPAMINE LEVELS; MEDIAL PREFRONTAL CORTEX; VENTRAL TEGMENTAL AREA; NUCLEUS-ACCUMBENS; TYROSINE-HYDROXYLASE; GLUCOSE-UTILIZATION; GENE-EXPRESSION; REWARD REGIONS; PRECURSOR POOL; BRAIN REWARD AB Single or repeated treatments with cocaine (15 mg/kg, i.p.) in rats modify rates of local cerebral protein synthesis (ICPSleu) measured with the [1-C-14]leucine method. A single dose of cocaine to naive rats reduced ICPSleu by about 10% throughout the brain; the most statistically significant reduction was in the nucleus accumbens, shell portion (P = .0003). A comparable dose of cocaine administered acutely after 1 wk of daily cocaine injections had no effects on ICPSleu. Delayed effects of prior chronic cocaine treatment were studied in experiments in which one rat of each pair received injections with saline for 8 days and the other cocaine, and on the 15th day ICPSleu was measured. In these experiments delayed effects of the chronic cocaine treatment were observed; in the cocaine-treated rats ICPSleu was significantly increased in selective brain regions, i.e., prefrontal and primary olfactory cortex (P < .006). These results suggest that acute effects of a single dose of cocaine and residual effects of chronic cocaine treatment on ICPSleu are distinctly different and occur in different regions of the brain. C1 NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. NIMH,DIV EPIDEMIOL & SERV RES,BETHESDA,MD 20892. UNIV ROMA LA SAPIENZA,DIPARTIMENTO SCI NEUROL,NEUROL CLIN,ROME,ITALY. NR 48 TC 6 Z9 6 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD FEB PY 1995 VL 272 IS 2 BP 892 EP 900 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QG057 UT WOS:A1995QG05700054 PM 7853207 ER PT J AU PEARSON, JD MORRELL, CH GORDONSALANT, S BRANT, LJ METTER, EJ KLEIN, LL FOZARD, JL AF PEARSON, JD MORRELL, CH GORDONSALANT, S BRANT, LJ METTER, EJ KLEIN, LL FOZARD, JL TI GENDER DIFFERENCES IN A LONGITUDINAL-STUDY OF AGE-ASSOCIATED HEARING-LOSS SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID EXPOSED POPULATION NINEP; THRESHOLDS; COHORT; MODELS RP PEARSON, JD (reprint author), NIA,GERONTOL RES CTR,LONGITUDINAL STUDIES BRANCH,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. RI Fozard, James Leonard/B-3660-2009 NR 47 TC 159 Z9 169 U1 0 U2 13 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD FEB PY 1995 VL 97 IS 2 BP 1196 EP 1205 DI 10.1121/1.412231 PG 10 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA QE936 UT WOS:A1995QE93600052 PM 7876442 ER PT J AU GERSH, BJ CHESEBRO, JH BRAUNWALD, E LAMBREW, C PASSAMANI, E SOLOMON, RE ROSS, AM ROSS, R TERRIN, ML KNATTERUD, GL AF GERSH, BJ CHESEBRO, JH BRAUNWALD, E LAMBREW, C PASSAMANI, E SOLOMON, RE ROSS, AM ROSS, R TERRIN, ML KNATTERUD, GL TI CORONARY-ARTERY-BYPASS GRAFT-SURGERY AFTER THROMBOLYTIC THERAPY IN THE THROMBOLYSIS IN MYOCARDIAL-INFARCTION TRIAL, PHASE-II (TIMI-II) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID TISSUE PLASMINOGEN-ACTIVATOR; IMPROVED SURVIVAL; RANDOMIZED TRIAL; FOLLOW-UP; ANGIOPLASTY; REVASCULARIZATION; REPERFUSION; IMMEDIATE; ANGINA; NETHERLANDS AB Objectives. We examined the results of coronary artery bypass graft surgery after thrombolytic therapy in the Thrombolysis in Myocardial Infarction trial, Phase II (TIMI II) with particular emphasis on patient characteristics, the impact of antecedent percutaneous transluminal coronary angioplasty and morbidity and mortality in certain subgroups. Background. Coronary bypass surgery is frequently used after thrombolytic therapy, but there is relatively little information with regard to early and late outcomes. Methods. We analyzed 3,339 patients enrolled in the TIMI II trial. Bypass surgery was performed in 390 patients (11.7%): 54 (14%) within 24 h after entry into the trial or within 24 h of coronary angioplasty and 336 (86%) between 24 h and 42 days after entry. Results. Perioperative mortality rates were, respectively, 16.7% and 3.9% (p < 0.001); perioperative myocardial infarction rates were 5.6% and 6.2%, respectively; and major hemorrhagic events occurred in 74% and 50.9%, respectively (p = 0.002). On multivariate analysis, the only independent predictor of perioperative mortality was bypass surgery within 23 h after entry or after coronary angioplasty. Among patients undergoing bypass surgery within 24 h of entry or after coronary angioplasty, the prevalence of multivessel disease (59.1% vs. 77.8%) and use of the internal thoracic artery (18.5% vs. 62.5%) were lower than in the remaining surgical patients. Among the 322 perioperative survivors, the 1-year mortality rate after discharge was only 2.2% and 1.9%, respectively, in the two groups. Only one patient had a documented recurrent myocardial infarction during the first year. Conclusions. The increased mortality rate with bypass surgery after thrombolytic therapy, particularly in patients undergoing operation within 24 h of coronary angioplasty or during the involving phase of infarction, must be balanced against the excellent 1-year prognosis and perioperative survivors, who are in general a group at higher risk of death or recurrent infarction. These data provide a basis for comparison for future studies. C1 MAYO CLIN & MAYO FDN,ROCHESTER,MN. BRIGHAM & WOMENS HOSP,BOSTON,MA. MAINE MED CTR,PORTLAND,ME. NHLBI,BETHESDA,MD. GEORGE WASHINGTON UNIV,WASHINGTON,DC. RP GERSH, BJ (reprint author), MARYLAND MED RES INST,TIMI COORDINATING CTR,600 WYNDHURST AVE,BALTIMORE,MD 21210, USA. NR 50 TC 20 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1995 VL 25 IS 2 BP 395 EP 402 DI 10.1016/0735-1097(94)00387-6 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA QD982 UT WOS:A1995QD98200016 PM 7829793 ER PT J AU BAUM, BJ OCONNELL, BC AF BAUM, BJ OCONNELL, BC TI THE IMPACT OF GENE-THERAPY ON DENTISTRY SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID CYSTIC-FIBROSIS; EXPRESSION; KERATINOCYTES; DELIVERY; INVIVO AB To the casual observer, gene therapy-an emerging science-appears likely to have little impact on dentistry. gene therapy will have a broad effect on dentistry. This article is designed to provide the practitioner with a general understanding of gene therapy, as well as several examples of how it is being used today in efforts to manage dental and oral problems better. RP BAUM, BJ (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,BLDG 10,BETHESDA,MD 20892, USA. OI O'Connell, Brian/0000-0003-4529-7664 NR 33 TC 31 Z9 32 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD FEB PY 1995 VL 126 IS 2 BP 179 EP 189 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA QF456 UT WOS:A1995QF45600012 PM 7860886 ER PT J AU FLEG, JL AF FLEG, JL TI DIAGNOSTIC AND PROGNOSTIC VALUE OF STRESS-TESTING IN OLDER PERSONS SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID CORONARY-ARTERY DISEASE; ACUTE MYOCARDIAL-INFARCTION; EXERCISE ECHOCARDIOGRAPHY; ELDERLY PATIENTS; ANGINA-PECTORIS; AGE; TL-201; SCINTIGRAPHY; TOMOGRAPHY; ADENOSINE AB OBJECTIVE: To review the diagnostic and prognostic utility of exercise and pharmacologic stress testing in older individuals. DATA SOURCE: A computer-assisted search of the literature, followed by a manual reference review of pertinent articles. STUDY SELECTION: Studies addressing the use of exercise and pharmacologic stress testing for coronary artery disease (CAD) detection and prognosis were reviewed. Emphasis was placed on those studies applying these procedures to older populations. DATA EXTRACTION: Pertinent data were extracted regarding the diagnostic and prognostic accuracy and safety of exercise and nonexercise stress testing techniques in older patients. DATA SYNTHESIS: Available data from relevant articles were summarized and the merits and limitations of the available techniques discussed. CONCLUSIONS: Numerous studies over the past 2 decades support the usefulness of the exercise ECG and exercise thallium-201 perfusion scan for detecting CAD in older populations. Although exercise echocardiography generally appears to have diagnostic and prognostic accuracy similar to thallium-201 imaging, greater technical difficulty with this technique is frequently encountered in older patients. Nonexercise forms of stress testing, particularly those employing pharmacologic agents such as dipyridamole, adenosine, or dobutamine, combined with either thallium-201 scintigraphy or echocardiography, allow accurate CAD diagnostic and prognostic assessment in even very frail older patients. Additional studies are needed to compare the accuracy and cost-benefit ratio of the many stress testing modalities now available for older patients. RP FLEG, JL (reprint author), NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 55 TC 7 Z9 7 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD FEB PY 1995 VL 43 IS 2 BP 190 EP 194 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA QF230 UT WOS:A1995QF23000018 PM 7836648 ER PT J AU YANG, CW HATTORI, M VLASSARA, H HE, CJ CAROME, MA YAMATO, E ELLIOT, S STRIKER, GE STRIKER, LJ AF YANG, CW HATTORI, M VLASSARA, H HE, CJ CAROME, MA YAMATO, E ELLIOT, S STRIKER, GE STRIKER, LJ TI OVEREXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA-1 MESSENGER-RNA IS ASSOCIATED WITH UP-REGULATION OF GLOMERULAR TENASCIN AND LAMININ GENE-EXPRESSION IN NONOBESE DIABETIC MICE SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE GLOMERULOSCLEROSIS; COMPETITIVE POLYMERASE CHAIN REACTION; EXTRACELLULAR MATRIX; GROWTH FACTOR; ADVANCED GLYCOSYLATION ENDPRODUCTS ID EXTRACELLULAR-MATRIX PROTEIN; GLYCOSYLATION END-PRODUCTS; MESSENGER-RNA LEVELS; SMOOTH-MUSCLE CELLS; FACTOR-BETA; HUMAN GLOMERULOSCLEROSIS; ANGIOTENSIN-II; IV COLLAGEN; RATS; KIDNEY AB Nonobese diabetic (NOD) mice spontaneously develop immune-mediated insulin-dependent diabetes mellitus and nephropathy, providing an opportunity to study the early molecular events in a model of diabetic glomerulosclerosis. The expression of several genes coding for growth factors and extracellular matrix was examined in microdissected glomeruli, by the use of reverse transcription-competitive polymerase chain reaction, in diabetic NOD mice (mean duration of diabetes, 28.5 +/- 7 days) and age-matched nondiabetic NOD mice with normal glucose tolerance. The levels of mRNA coding for transforming growth factor-beta 1, tenascin, and laminin B1 increased 1.9-, 2.0-, and 1.7-fold, respectively, whereas platelet-derived growth factor (PDGF)-B, alpha 1(IV) collagen, 72-kd collagenase, alpha-smooth muscle actin, and beta-actin mRNA remained stable in the diabetic mice. The kidney advanced glycosylation endproducts levels increased 2.1-fold in the diabetic mice, and the diabetic glomeruli showed an accumulation of tenascin and laminin but not of type IV collagen by immunofluorescence microscopy. There was no increase in cell number per glomerulus after the onset of diabetes, a finding consistent with stable PDGF-B and alpha-smooth muscle actin mRNA levels. These findings provide evidence that increased glomerular transforming growth factor-beta 1, but not PDGF-B, mRNA is associated with the up-regulation of tenascin and laminin expression after advanced glycosylation endproduct accumulation, early after the onset of diabetes. C1 NIDDKD,METAB DIS BRANCH,RENAL CELL BIOL SECT,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,IMMUNOL & IMMUNOGENET SECT,BOSTON,MA 02115. PICOWER INST MED RES,MANHASSET,NY. WALTER REED ARMY MED CTR,DEPT MED,WASHINGTON,DC 20307. FU NIA NIH HHS [5 RO1 AGO4953-04]; NIDDK NIH HHS [R01DK43613, DK36836] NR 54 TC 86 Z9 87 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD FEB PY 1995 VL 5 IS 8 BP 1610 EP 1617 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA QH761 UT WOS:A1995QH76100011 PM 7538809 ER PT J AU DEVESA, SS AF DEVESA, SS TI STAT BITE - CANCER RATES FOR US WHITES 1973-1991 SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material RP DEVESA, SS (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,RM 415,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD FEB 1 PY 1995 VL 87 IS 3 BP 168 EP 168 DI 10.1093/jnci/87.3.168 PG 1 WC Oncology SC Oncology GA QD408 UT WOS:A1995QD40800006 ER PT J AU DEVESA, SS BLOT, WJ STONE, BJ MILLER, BA TARONE, RE FRAUMENI, JF AF DEVESA, SS BLOT, WJ STONE, BJ MILLER, BA TARONE, RE FRAUMENI, JF TI RECENT CANCER TRENDS IN THE UNITED-STATES SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; BREAST-CANCER; PROSTATE-CANCER; YOUNG MEN; MORTALITY; COHORT; RATES; RISK; MESOTHELIOMA; PATTERNS AB Background: Cancer incidence rates have been reported to be increasing in the United States, although trends vary according to form of cancer, Purpose: We identify the cancers accounting for the rising incidence, quantify the changes that have occurred from the mid-1970s to the early 1990s, and contrast incidence and mortality trends to provide clues to the determinants of the temporal patterns, Methods: Sex-, race-, and age-specific and age-adjusted incidence rates for the 5-year periods 1987-1991 versus 1975-1979 were calculated for 28 cancers among men and 30 cancers among women using data from the Surveillance, Epidemiology, and End Results (SEER) Program of cancer registration covering about 10% of the U.S. population, Similar rates were computed using national mortality data, Cancers were ranked according to the change in incidence rates over the two periods, Results: Age-adjusted incidence rates for all cancers combined increased by 18.6% among males and 12.4% among females from 1975-1979 to 1987-1991, due large ly to rising rates for prostate cancer among men and for breast and lung cancers among women, National mortality rates for all cancers combined rose less steeply, 3% and 6% among men and women, respectively, driven mostly by continuing increases in lung cancer mortality, while death rates for the majority of the cancers were steady or declining, Total cancer incidence rose at all ages, but with different tumors responsible for the increases at different ages: leukemia and brain/nervous system cancer among children; testicular cancer, nonmelanoma skin cancer (largely Kaposi's sarcoma), non Hodgkin's lymphoma, and melanoma noma among young and middle aged adults; and prostate, breast, and lung cancers among older individuals. In contrast, mortality rates for all cancers combined declined among both males and females under age 55 years, increasing only among older persons, Conclusions: Trends in cancer incidence and mortality differ, For most cancers, incidence rates are rising, while mortality rates are generally stable or declining, Implications: Much of the recent increase in cancer incidence can be explained by known factors, Improved proved detection appears to account for most of the in creases in breast cancer among women and prostate cancer among men, On the other hand, cigarette Smoking is the major determinant of the rise in lung cancer among women, acquired immunodeficiency syndrome has led to increases in non Hodgkin's lymphoma and Kaposi's sarcoma among young and middle-aged men, and sunlight exposure patterns have affected the trends in melanoma. Some trends remain unexplained, however, and may reflect changing exposures to carcinogens yet to be identified and clarified. C1 NCI,DIV CANC PREVENT & CONTROL,SURVEILLANCE PROGRAM,BETHESDA,MD 20892. RP DEVESA, SS (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,RM 415,BETHESDA,MD 20892, USA. NR 52 TC 311 Z9 319 U1 0 U2 9 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 FEB 1 PY 1995 VL 87 IS 3 BP 175 EP 182 DI 10.1093/jnci/87.3.175 PG 8 WC Oncology SC Oncology GA QD408 UT WOS:A1995QD40800009 PM 7707404 ER PT J AU BELL, DA LIU, YF CORTOPASSI, GA AF BELL, DA LIU, YF CORTOPASSI, GA TI OCCURRENCE OF BCL-2 ONCOGENE TRANSLOCATION WITH INCREASED FREQUENCY IN THE PERIPHERAL-BLOOD OF HEAVY SMOKERS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Note ID NON-HODGKINS-LYMPHOMA; MULTIPLE-MYELOMA; RISK; AMPLIFICATION; T(14-18); SMOKING; CELLS C1 NIEHS,BIOCHEM RISK ANAL LAB,RES TRIANGLE PK,NC 27709. FU NCI NIH HHS [CA56407] NR 16 TC 87 Z9 91 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 FEB 1 PY 1995 VL 87 IS 3 BP 223 EP 224 DI 10.1093/jnci/87.3.223 PG 2 WC Oncology SC Oncology GA QD408 UT WOS:A1995QD40800016 PM 7707410 ER PT J AU CANTOR, KP DOSEMECI, M BRINTON, LA STEWART, PA AF CANTOR, KP DOSEMECI, M BRINTON, LA STEWART, PA TI BREAST-CANCER MORTALITY AMONG FEMALE ELECTRICAL WORKERS IN THE UNITED-STATES SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter RP CANTOR, KP (reprint author), NCI,DIV CANC ETIOL,ENVIRONM EPIDEMIOL BRANCH,EXECUT PLAZA N,RM 443,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 3 TC 23 Z9 23 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 FEB 1 PY 1995 VL 87 IS 3 BP 227 EP 228 DI 10.1093/jnci/87.3.227 PG 2 WC Oncology SC Oncology GA QD408 UT WOS:A1995QD40800017 PM 7707411 ER PT J AU NOMEIR, AA SILVEIRA, DM FERRALA, NF MARKHAM, PM MCCOMISH, MF GHANAYEM, BI CHADWICK, M AF NOMEIR, AA SILVEIRA, DM FERRALA, NF MARKHAM, PM MCCOMISH, MF GHANAYEM, BI CHADWICK, M TI COMPARATIVE DISPOSITION OF 2,3-EPOXY-1-PROPANOL (GLYCIDOL) IN RATS FOLLOWING ORAL AND INTRAVENOUS ADMINISTRATION SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH LA English DT Article ID ALPHA-CHLOROHYDRIN; METABOLISM; SPERMATOZOA; CARCINOGENS; EXCRETION; ASSAY AB Glycidol (2,3-epoxy-1-propanol), an industrial chemical, has Been shown to be a reproductive toxicant in short-term studies and a carcinogen in rats and mice in oncogenicity studies. The reproductive toxicity of glycidol was believed to result from its conversion to alpha-chlorohydrin by the action of HCl in the stomach. The comparative disposition of glycidol was investigated in rats following oral (po) or intravenous (iv) administration at doses of 37.5 and 75 mg/kg. These were the doses used in the National Toxicology Program (NTP) oncogenicity study with glycidol. Approximately 87-92% of the dose was absorbed from the gastrointestinal tract of the rat. [C-14]Glycidol equivalents were eliminated in urine (40-48% or dose in 72 h) feces (5-12%) and exhaled as CO2 (26-32%). Al both doses, 9-12% and 7-8% (estimated) of the dose remained in tissues at 24 and 72 h following dosing, respectively. In general, the concentrations of glycidol equivalents in tissues were proportional to the dose. The highest concentrations of radioactivity were observed in blood cells, thyroid, liver, kidney, and spleen, and the lowest in adipose tissue, skeletal muscle, and plasma. The pattern of distribution of radioactivity in tissues was similar for both tile iv and po routes. The total recovery oi radioactivity ranged from 87 to 91% of dose. Urinary radioactivity was resolved by high-performance liquid chromatography (HPLC) analysis into 15 metabolites. There were one major (14-21% of the dose) and four lesser metabolites (each representing 2-8%); the others were minor, each representing 1% or less of the dose. In general, the urinary metabolic profile was similar following either iv or po administration at the two doses studied. Previous studies by other investigators suggested that alpha-chlorohydrin, which was presumably formed from glycidol by the HCl in the stomach, was metabolized and excreted in urine as beta-chlorolactic acid. The results of the present study show that very little, if any, urinary radioactivity coeluted with authentic beta-chlorolactic acid following either iv or po administration. Therefore, it is concluded that the conversion of glycidol to alpha-chlorohydrin is quantitatively insignificant. However, it may be significant with regard to glycidol reproductive toxicity. Also, the NTP oncogenicity study with glycidol was carried out within the dose range in which its disposition characteristics were linear. C1 ARTHUR D LITTLE INC,CAMBRIDGE,MA. NIEHS,RES TRIANGLE PK,NC. FU NIEHS NIH HHS [N01-ES-65138] NR 34 TC 16 Z9 16 U1 2 U2 3 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0098-4108 J9 J TOXICOL ENV HEALTH JI J. Toxicol. Environ. Health PD FEB PY 1995 VL 44 IS 2 BP 203 EP 217 PG 15 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA QK642 UT WOS:A1995QK64200005 PM 7853422 ER PT J AU MARKOWITZ, M MO, HM KEMPF, DJ NORBECK, DW BHAT, TN ERICKSON, JW HO, DD AF MARKOWITZ, M MO, HM KEMPF, DJ NORBECK, DW BHAT, TN ERICKSON, JW HO, DD TI SELECTION AND ANALYSIS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-I VARIANTS WITH INCREASED RESISTANCE TO ABT-538, A NOVEL PROTEASE INHIBITOR SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; REDUCED SENSITIVITY; VIRAL INFECTIVITY; ZIDOVUDINE AZT; PROTEINASE; CELLS; PARTICLES; THERAPY; DESIGN AB Inhibitors of the human immunodeficiency virus protease represent a promising new class of antiretroviral drugs for the treatment of AIDS. We now report the in vitro selection of viral variants with decreased sensitivity to a symmetry-based protease inhibitor, ABT-538, currently being tested in clinical trials. Molecular characterization of the variants shows that an isoleucine-to-valine substitution at position 84 results in a substantial decrease in sensitivity to the drug. Moreover, an additional mutation at position 82, valine to phenylalanine, further decreases viral susceptibility to ABT-538. Three-dimensional analysis of the protease-drug complex provides a structural explanation for the relative drug resistance induced by these two mutations. These findings emphasize the importance of closely monitoring patients receiving ABT-538 for the emergence of viral resistance and provide information that may prove useful in designing the nest generation of protease inhibitors. C1 NYU,SCH MED,AARON DIAMOND AIDS RES CTR,NEW YORK,NY 10016. ABBOTT LABS,DIV PHARMACEUT PROD,ANTIINFECT RES,ABBOTT PK,IL 60064. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702. FU NIAID NIH HHS [AI 132427, AI 07382, AI 125541] NR 36 TC 210 Z9 214 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1995 VL 69 IS 2 BP 701 EP 706 PG 6 WC Virology SC Virology GA QB860 UT WOS:A1995QB86000010 PM 7815532 ER PT J AU RAY, NB EWALT, LC LODMELL, DL AF RAY, NB EWALT, LC LODMELL, DL TI RABIES VIRUS-REPLICATION IN PRIMARY MURINE BONE-MARROW MACROPHAGES AND IN HUMAN AND MURINE MACROPHAGE-LIKE CELL-LINES - IMPLICATIONS FOR VIRAL PERSISTENCE SO JOURNAL OF VIROLOGY LA English DT Article ID CENTRAL NERVOUS-SYSTEM; PERITONEAL-MACROPHAGES; GENE-EXPRESSION; LEUKEMIA-CELLS; INFECTION; DIFFERENTIATION; RESISTANCE; INDUCTION; ANTIBODY; INVITRO AB To determine whether rabies viruses replicate in macrophage or macrophage-like cells, several human and murine macrophage-like cell lines, as well as primary cultures of murine bone marrow macrophages, were incubated with the Evelyn-Rokitnicki-Abelseth (ERA) virus and several different street rabies viruses (SRV). ERA rabies virus replicated well in human monocytic U937 and THP-1 cells and murine macrophage IC-21 cells, as well as primary cultures of murine macrophages. Minimal replication was detected in murine monocytic WEHI-3BD(-) and PU5-1R cells, and ERA virus did not replicate in murine monocytic P388D1 or J774A.1 cells. A tissue culture-adapted SRV of bat origin also replicated in IC-21 and U937 cells. Non-tissue culture-adapted SRV isolated from different animal species, particularly bats, replicated minimally in U937, THP-1, IC-21 cells and primary murine bone marrow macrophages. To determine whether rabies virus replication is dependent upon the state of differentiation of the macrophage-like cell, human promyelocytic HL-60 cells were differentiated with 12-O-tetradecanoylphorbol-13-acetate (TPA). ERA rabies virus replicated in the differentiated HL-60 cells but not in undifferentiated HL-60 cells. Persistent infections were established in macrophage-like U937 cells with ERA rabies virus and SRV, and infectious SRV was isolated from adherent bone marrow cells of mice that had been infected 96 days previously, Virus harvested from persistently infected U937 cells and the adherent bone marrow cells had specifically adapted to each cell. This specificity was shown by the inability of the viruses to infect macrophages other than U937 cells and primary bone marrow macrophages, respectively. Virus titers of the persistently infected U937 cells fluctuated with extended cell passage. After 30 passages, virus released from the cells had lost virulence as shown by its inability to kill intracranially inoculated mice. However, the avirulent virus released from the persistently infected cells was more efficient in infecting and replicating in naive U937 cells than the virus which was used to establish the persistent infection. These results suggest that macrophages may serve as reservoirs of infection in vivo, sequestering virus which may subsequently be activated from its persistent state, resulting in clinical infection and death. C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. NR 42 TC 36 Z9 38 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1995 VL 69 IS 2 BP 764 EP 772 PG 9 WC Virology SC Virology GA QB860 UT WOS:A1995QB86000019 PM 7815541 ER PT J AU HARRIS, N BULLER, RML KARUPIAH, G AF HARRIS, N BULLER, RML KARUPIAH, G TI GAMMA-INTERFERON-INDUCED, NITRIC OXIDE-MEDIATED INHIBITION OF VACCINIA VIRUS-REPLICATION SO JOURNAL OF VIROLOGY LA English DT Article ID ACTIVATED MACROPHAGES; RIBONUCLEOTIDE REDUCTASE; MURINE MACROPHAGES; NEOPLASTIC-CELLS; PROTEIN-KINASE; PRODUCT; RNA; EXPRESSION; SYNTHASE; SYSTEM AB Gamma interferon (IFN-gamma)-induced nitric oxide synthase (iNOS) and nitric oxide (NO) production in the murine macrophage-like RAW 264.7 cells were previously shown to inhibit the replication of the poxviruses vaccinia virus (VV) and ectromelia virus and herpes simplex virus type 1. In the current study, we performed biochemical analyses to determine the stage in the viral life cycle blocked by IFN-gamma-induced NO, Antibodies specific for temporally expressed viral proteins, a VV-specific DNA probe, and transmission electron microscopy were used to show that the cytokine-induced NO inhibited late protein synthesis, DNA replication, and virus particle formation but not expression of the early proteins analyzed. Essentially similar results were obtained with hydroxyurea and cytosine arabinoside, inhibitors of DNA replication. Enzymatically active iNOS was detected in the lysates of IFN-gamma-treated but not in untreated RAW 264.7 cells. The IFN-gamma-treated RAW 264.7 cells which express iNOS not only were resistant to productive infection but also efficiently blocked the replication of VV in infected bystander cells of epithelial origin. This inhibition was arginine dependent, correlated with nitrite production in cultures, and was reversible by the NOS inhibitor N-omega-monomethyl-L-arginine. C1 NIAID, VIRAL DIS LAB, BETHESDA, MD 20892 USA. RI Karupiah, Gunasegaran/J-4707-2013 NR 44 TC 135 Z9 140 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1995 VL 69 IS 2 BP 910 EP 915 PG 6 WC Virology SC Virology GA QB860 UT WOS:A1995QB86000038 PM 7529336 ER PT J AU HIRSCH, VM DAPOLITO, G JOHNSON, PR ELKINS, WR LONDON, WT MONTALI, RJ GOLDSTEIN, S BROWN, C AF HIRSCH, VM DAPOLITO, G JOHNSON, PR ELKINS, WR LONDON, WT MONTALI, RJ GOLDSTEIN, S BROWN, C TI INDUCTION OF AIDS BY SIMIAN IMMUNODEFICIENCY VIRUS FROM AN AFRICAN-GREEN MONKEY - SPECIES-SPECIFIC VARIATION IN PATHOGENICITY CORRELATES WITH THE EXTENT OF IN-VIVO REPLICATION SO JOURNAL OF VIROLOGY LA English DT Article ID RHESUS-MONKEYS; MACAQUE MONKEYS; EXPERIMENTAL-INFECTION; GENETIC DIVERSITY; HIGHLY DIVERGENT; SOOTY MANGABEYS; PROVIRAL DNA; ANTIBODIES; DISEASE; SIVAGM AB Previous studies suggested that simian immunodeficiency viruses isolated from African green monkeys (SIVagm) are relatively nonpathogenic. The report describes the isolation and biologic and molecular characterization of a pathogenic SIVagm strain derived from a naturally infected African green monkey. This virus induced an AIDS-like syndrome characterized by early viremia, frequent thrombocytopenia, severe lymphoid depletion, opportunistic infections, meningoencephalitis, and death of five of eight macaques within 1 year after infection. An infectious clone derived from this isolate reproduced the immunodeficiency disease in pig-tailed (PT) macaques, providing definitive proof of the etiology of this syndrome. Although the virus was highly pathogenic in PT macaques, no disease was observed in experimentally infected rhesus macaques and African green monkeys despite reproducible infection of the last two species. Whereas infection of PT macaques was associated with a high viral load in plasma, peripheral blood mononuclear cells, and tissues, low-level viremia and infrequent expression in lymph nodes of rhesus macaques and African green monkeys suggest that differences in pathogenicity are associated with the extent of in vivo replication. The availability of a pathogenic molecular clone will provide a useful model for the study of viral and host factors that influence pathogenicity. C1 GEORGETOWN UNIV,SCH MED,DEPT MICROBIOL,DIV MOLEC VIROL & IMMUNOL,ROCKVILLE,MD 20852. OHIO STATE UNIV,CHILDRENS HOSP RES FDN,DEPT PEDIAT,COLUMBUS,OH 43205. HENRY M JACKSON FDN,ROCKVILLE,MD 20850. RP HIRSCH, VM (reprint author), NIAID,INFECT DIS LAB,IMMUNODEFICIENCY VIRUSES SECT,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. RI Johnson, Philip/A-6892-2009 NR 40 TC 188 Z9 188 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1995 VL 69 IS 2 BP 955 EP 967 PG 13 WC Virology SC Virology GA QB860 UT WOS:A1995QB86000043 PM 7815563 ER PT J AU AHMAD, N BAROUDY, BM BAKER, RC CHAPPEY, C AF AHMAD, N BAROUDY, BM BAKER, RC CHAPPEY, C TI GENETIC-ANALYSIS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE V3 REGION ISOLATES FROM MOTHERS AND INFANTS AFTER PERINATAL TRANSMISSION SO JOURNAL OF VIROLOGY LA English DT Article ID POSTNATAL TRANSMISSION; SEQUENCE HETEROGENEITY; MATERNAL ANTIBODIES; PRIMARY INFECTION; HIV-1 INFECTION; DETERMINANT; GP120; BORN; LOOP; RNA AB The human immunodeficiency virus type 1 (HIV-1) sequences from variable region 3 (V3) Of the envelope gene were analyzed from seven infected mother-infant pairs following perinatal transmission. The V3 region sequences directly derived from the DNA of the uncultured peripheral blood mononuclear cells from infected mothers displayed a heterogeneous population. In contrast, the infants' sequences were less diverse than those of their mothers. In addition, the sequences from the younger infants' peripheral blood mononuclear cell DNA were more homogeneous than the older infants' sequences. All infants' sequences were different but displayed patterns similar to those seen in their mothers. In the mother-infant pair sequences analyzed, a minor genotype or subtype found in the mothers predominated in their infants. The conserved N-linked glycosylation site proximal to the first cysteine of the V3 loop,vas absent only in one infant's sequence set and in some variants of two other infants' sequences. Furthermore, the HIV-1 sequences of the epidemiologically linked mother-infant pairs were closer than the sequences of epidemiologically unlinked individuals, suggesting that the sequence comparison of mother-infant pairs done in order to identify genetic variants transmitted from mother to infant could be performed even in older infants. There was no evidence for transmission of a major genotype or multiple genotypes from mother to infant. In conclusion, a minor genotype of maternal virus is transmitted to the infants, and this finding could be useful in developing strategies to prevent maternal transmission of HIV-1 by means of perinatal interventions. C1 JAMES N GAMBLE INST MED RES,DIV MOLEC VIROL,CINCINNATI,OH 45219. CHILDRENS HOSP,MED CTR,DIV GEN PEDIAT,CINCINNATI,OH 45229. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. RP AHMAD, N (reprint author), UNIV ARIZONA,ARIZONA HLTH SCI CTR,COLL MED,DEPT MICROBIOL & IMMUNOL,TUCSON,AZ 85724, USA. NR 52 TC 123 Z9 123 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1995 VL 69 IS 2 BP 1001 EP 1012 PG 12 WC Virology SC Virology GA QB860 UT WOS:A1995QB86000048 PM 7815476 ER PT J AU KULKARNI, AB COLLINS, PL BACIK, I YEWDELL, JW BENNINK, JR CROWE, JE MURPHY, BR AF KULKARNI, AB COLLINS, PL BACIK, I YEWDELL, JW BENNINK, JR CROWE, JE MURPHY, BR TI CYTOTOXIC T-CELLS SPECIFIC FOR A SINGLE PEPTIDE ON THE M2 PROTEIN OF RESPIRATORY SYNCYTIAL VIRUS ARE THE SOLE MEDIATORS OF RESISTANCE INDUCED BY IMMUNIZATION WITH M2 ENCODED BY A RECOMBINANT VACCINIA VIRUS SO JOURNAL OF VIROLOGY LA English DT Note ID CLASS-II REGION; INFLUENZA NUCLEOPROTEIN; LYMPHOCYTES-T; ANTIGEN; MHC; RECOGNITION; INFECTION; TRANSPORTERS; EXPRESSION; EPITOPE AB We have studied the immunobiology of respiratory syncytial virus (RSV), a major cause of respiratory tract morbidity in children. As part of these studies, it was previously found that immunization of BALB/c (H-2(d)) mice with a recombinant vaccinia virus (rVV) which encoded the M2 protein of RSV provided complete protection against infection with RSV. This protection was transient and associated with M2-specific CD8(+) T-cell (T-CD8+) responses. In this study, we used two approaches to demonstrate that expression of an H-2K(d)-restricted nonameric peptide (Ser Tyr Ile Gly Ser Ile Asn Asn Ile) corresponding to M2 residues 82 to 90 is necessary and sufficient to induce protective T-CD8+ responses. First, infection of mice with an rVV which encoded the peptide M2(Met82-90) induced levels of primary pulmonary T-CD8+ and resistance to RSV challenge equivalent to that induced by infection with an rVV which expressed the complete M2 protein. Second, elimination of peptide binding to K-d by the replacement of Tyr with Arg at amino acid position 83 of the full-length protein completely abrogated the ability of an rVV-expressing full-length M2 to induce either M2-specific T-CD8+ responses or resistance to RSV infection. These findings demonstrate that the M2(82-90) peptide is the sole determinant of immunity induced in BALB/c mice by the M2 protein and that a remarkably high level of transient resistance to infection with pulmonary virus is associated with T-CD8+ responses to a single determinant. C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. RI Crowe, James/B-5549-2009; yewdell, jyewdell@nih.gov/A-1702-2012 OI Crowe, James/0000-0002-0049-1079; NR 25 TC 84 Z9 84 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1995 VL 69 IS 2 BP 1261 EP 1264 PG 4 WC Virology SC Virology GA QB860 UT WOS:A1995QB86000079 PM 7815502 ER PT J AU BUCHSCHACHER, GL FREED, EO PANGANIBAN, AT AF BUCHSCHACHER, GL FREED, EO PANGANIBAN, AT TI EFFECTS OF 2ND-SITE MUTATIONS ON DOMINANT INTERFERENCE BY A HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE GLYCOPROTEIN MUTANT SO JOURNAL OF VIROLOGY LA English DT Note ID CYTOPLASMIC DOMAIN; MEMBRANE-FUSION; GENE; REPLICATION; CLEAVAGE; PROTEIN; INFECTIVITY; ACTIVATION; RECEPTOR; VECTORS AB We have demonstrated previously that a human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein containing a Val-to-Glu substitution at the second amino acid of the transmembrane glycoprotein gp41 (termed the 41.2 mutant) dominantly interferes with wild type envelope-mediated syncytium formation and virus infectivity. To understand the mechanism by which the 41.2 mutant exerts the dominant interfering phenotype and thereby determine further how the mutant might be used as an inhibitor of viral spread, additional mutations were made in the envelope gene, and the effects of these mutations on interference were determined. It was found that processing of the 41.2 mutant glycoprotein to gp120 and gp41 subunits and a functional CD4-binding domain are necessary for the interfering phenotype to be exhibited fully. However, neither a wild-type V3 loop nor the gp41 cytoplasmic tail is necessary for efficient interference. In addition, it was determined that the dominant interfering phenotype is not conferred exclusively by the glutamate substitution at amino acid 2 of gp41, since a substitution with a basic residue at this position also results in a dominant interfering envelope glycoprotein. C1 UNIV WISCONSIN,MCARDLE LAB CANC RES,MADISON,WI 53706. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA22443] NR 25 TC 18 Z9 19 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1995 VL 69 IS 2 BP 1344 EP 1348 PG 5 WC Virology SC Virology GA QB860 UT WOS:A1995QB86000097 PM 7815519 ER PT J AU ROTHENPIELER, UW DRESSIER, GR AF ROTHENPIELER, UW DRESSIER, GR TI DOWN-REGULATION OF PAX-2 FOLLOWED BY WILMS-TUMOR PROTEIN (WT1) EXPRESSION DURING EARLY KIDNEY DEVELOPMENT SO KIDNEY INTERNATIONAL LA English DT Meeting Abstract C1 UNIV MUNICH,KLINIKUM INNENSTADT,MED POLIKLIN,W-8000 MUNICH,GERMANY. NICHHD,MAMMALIAN GENES & DEV LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 1995 VL 47 IS 2 BP 661 EP 661 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA QD321 UT WOS:A1995QD32100052 ER PT J AU ROBERTS, AB LETTERIO, JJ GEISER, AG ROCHE, NS KULKARNI, AB DSOUZA, R KARLSSON, S SPORN, MB AF ROBERTS, AB LETTERIO, JJ GEISER, AG ROCHE, NS KULKARNI, AB DSOUZA, R KARLSSON, S SPORN, MB TI WOUND-HEALING IN THE TGF-BETA-1 NULL MOUSE - EFFECTS OF MATERNAL TRANSFER OF TGF-BETA-1 AND INCREASED EXPRESSION OF TGF-BETA-2 AND TGF-BETA-3 SO KIDNEY INTERNATIONAL LA English DT Meeting Abstract C1 NINCDS,DEV & METAB NEUROL BRANCH,BETHESDA,MD 20892. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. UNIV TEXAS,DEPT BASIC SCI,HOUSTON,TX. NR 4 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 1995 VL 47 IS 2 BP 692 EP 692 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA QD321 UT WOS:A1995QD32100210 ER PT J AU SCHWAB, A KRAMER, A GABRIEL, K WOJNOWSKI, L GEKLE, M OBERLEITHNER, H AF SCHWAB, A KRAMER, A GABRIEL, K WOJNOWSKI, L GEKLE, M OBERLEITHNER, H TI CELL-VOLUME OSCILLATES DURING MIGRATION OF MDCK-F CELLS SO KIDNEY INTERNATIONAL LA English DT Meeting Abstract C1 PHYSIOL INST,WURZBURG,GERMANY. PHYSIOL INST,FREIBURG,GERMANY. NCI,FREDERICK,MD 21701. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 1995 VL 47 IS 2 BP 697 EP 697 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA QD321 UT WOS:A1995QD32100232 ER PT J AU KRIETE, MF CHAMPOUX, M SUOMI, SJ AF KRIETE, MF CHAMPOUX, M SUOMI, SJ TI DEVELOPMENT OF IRON-DEFICIENCY ANEMIA IN INFANT RHESUS MACAQUES SO LABORATORY ANIMAL SCIENCE LA English DT Article ID EARLY REARING CONDITIONS; HUMAN-MILK; RISK AB Although previous research has documented the occurrence of an iron deficiency anemia in infant nonhuman primates, the temporal development of this condition has not been studied to our knowledge, We conducted a retrospective analysis of complete blood count data obtained from 56 rhesus macaque infants over a 5-month period, Fourteen infants were exclusively mother-reared, and 42 were nursery-reared, By 60 days of age, erythrocyte indices were lower in the mother-reared monkeys than in the nursery-reared animals, Between 90 to 150 days of age, an apparent iron deficiency anemia developed in the mother-reared infants only, This anemia was characterized as a microcytic, hypochromic anemia, The time of onset of this anemia was comparable developmentally to that observed in exclusively breast-fed human infants, At no time were these infants clinically or behaviorally affected by the anemia, Hematologic status of the mothers did not correlate with that of their infants, It could not be determined whether mother's parity was predictive of the development of anemia in the infant, These observed phenomena in rhesus monkeys may serve as a potential nonhuman primate model for the anemia that is observed in exclusively breast-fed human infants. C1 NICHHD,COMPARAT ETHOL LAB,POOLESVILLE,MD. RP KRIETE, MF (reprint author), NEI,BETHESDA,MD 20892, USA. NR 34 TC 11 Z9 11 U1 1 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD FEB PY 1995 VL 45 IS 1 BP 15 EP 21 PG 7 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA QW949 UT WOS:A1995QW94900004 PM 7752609 ER PT J AU KU, WW CLARK, J MYERS, PH ADAMS, LN CHAPIN, RE AF KU, WW CLARK, J MYERS, PH ADAMS, LN CHAPIN, RE TI HISTOLOGIC LOCALIZATION OF SURGICALLY TRANSPLANTED SYNGENEIC SEMINIFEROUS TUBULE SEGMENTS INTO TESTIS WITH FAST-BLUE AS TRACER SO LABORATORY ANIMAL SCIENCE LA English DT Article ID DIFFERENTIATION; RAT; MICE AB Spermatogenesis is a complex differentiative process influenced by the testicular extratubular and intratubular tissue environments, One method of determining the relative importance of intratubular versus extratubular factors in cases of deficient spermatogenesis has been syngeneic seminiferous tubule transplantation, Generally in such a scheme, tubule segments from a testis deficient in spermatogenesis are transplanted into an intact recipient testis, and the progression of spermatogenesis in transplanted tubules is examined histologically, However, this experimental approach has been complicated by the tedious histologic serial sectioning required to locate these transplanted tubules and the need to distinguish them from recipient testis solely by structural differences, A method is described for the surgical transplantation of seminiferous tubule segments into rat testes that uses prelabeling donor tubules in vitro with the fluorescent tracer Fast Blue to facilitate their localization, The technique was evaluated by transplanting cut segments of Fast Blue-labeled seminiferous tubules from 15-day-old rat testis into normal adult rat testis (recipient), then localizing and histologically examining the progression of spermatogenesis in the transplanted tubules for up to 28 days, Transplanted tubules were easily identified in sections of recipient testis by fluorescent microscopy; intense Fast Blue staining with low background was seen up to 28 days after transplantation. Histologically, transplanted tubules had limited germ cell differentiation in recipient testis for the Fischer rat strain, At 10 days after transplantation, tubules had characteristics qualitatively similar to tubules from 25-day-old rat testis, with increased tubular diameter and abundant germ cells at the pachytene spermatocyte stage, At 28 days after transplantation, germ cell loss was evident in most transplanted tubules; some had evidence of germ cell progression to various spermatid stages, These results suggest that, at least in the short term for the Fischer rat strain, this method should make it easier to separate intratubular from extratubular defects in eases of deficient spermatogenesis or the lack of recovery after testicular damage. C1 NIEHS,ENVIRONM TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. NIEHS,COMPARAT MED BRANCH,RES TRIANGLE PK,NC 27709. OI Chapin, Robert/0000-0002-5997-1261 NR 16 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD FEB PY 1995 VL 45 IS 1 BP 81 EP 88 PG 8 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA QW949 UT WOS:A1995QW94900016 PM 7752621 ER PT J AU VOIT, ES AF VOIT, ES TI DEVELOPING A RESEARCH-PROGRAM - SHAH,SALEEM LEADERSHIP ROLE AT THE NATIONAL-INSTITUTE-OF-MENTAL-HEALTH SO LAW AND HUMAN BEHAVIOR LA English DT Article AB This article describes Saleem Shah's early professional years, his development of the Center for Studies of Crime and Delinquency at the National Institute of Mental Health, and his use of the Center to stimulate the growth and direction of research on law and mental health. RP VOIT, ES (reprint author), NIMH,DIV EPIDEMIOL & SERV RES,5600 FISHERS LANE,ROOM 10C-26,ROCKVILLE,MD 20857, USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0147-7307 J9 LAW HUMAN BEHAV JI Law Hum. Behav. PD FEB PY 1995 VL 19 IS 1 BP 5 EP 14 DI 10.1007/BF01499066 PG 10 WC Law; Psychology, Social SC Government & Law; Psychology GA QJ270 UT WOS:A1995QJ27000002 ER PT J AU KLIPPEL, JH AF KLIPPEL, JH TI CYCLOPHOSPHAMIDE - OVARIAN AND OTHER TOXICITIES SO LUPUS LA English DT Editorial Material ID SYSTEMIC LUPUS-ERYTHEMATOSUS; PULSE CYCLOPHOSPHAMIDE; CONTROLLED TRIAL; NEPHRITIS; CHEMOTHERAPY; THERAPY; PROTECTION; WOMEN; RATS RP KLIPPEL, JH (reprint author), NIH,CLIN INVEST SECT,ARTHRITIS & RHEUMATISM BRANCH,BETHESDA,MD 20892, USA. NR 22 TC 7 Z9 7 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0961-2033 J9 LUPUS JI Lupus PD FEB PY 1995 VL 4 IS 1 BP 1 EP 2 DI 10.1177/096120339500400101 PG 2 WC Rheumatology SC Rheumatology GA QR062 UT WOS:A1995QR06200001 PM 7767331 ER PT J AU SCHOLZ, TD HOYT, RF DELEONARDIS, JR CECKLER, TL BALABAN, RS AF SCHOLZ, TD HOYT, RF DELEONARDIS, JR CECKLER, TL BALABAN, RS TI WATER-MACROMOLECULAR PROTON MAGNETIZATION-TRANSFER IN INFARCTED MYOCARDIUM - A METHOD TO ENHANCE MAGNETIC-RESONANCE IMAGE-CONTRAST SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE CARDIAC; RELAXATION TIMES; INFARCTION ID PULSED SATURATION; CROSS-RELAXATION; INVIVO; SIZE; DISEASE; HEART AB Water proton nuclear magnetic resonance relaxation times and magnetization transfer (MT)-parameters of rat hearts were studied 24 h or 4 weeks after ligation of the left coronary artery or sham operation. Compared with sham-operated controls, measured relaxation times (T-1sat, and T-2) of both acute and chronic myocardial infarction increased. The MT effect significantly decreased in the infarcted myocardium. The changes in relaxation times and MT effect were significantly greater in chronic infarcts compared with acute infarcts. Improvements in calculated image contrast between normal and infarcted tissue were supported by images of ex vivo hearts with chronic infarction. Image contrast was increased at short echo times in the presence of macromolecular proton pool irradiation. Exploiting changes in tissue MT following myocardial infarction to enhance contrast between normal and infarcted tissue should allow improved identification and characterization of infarcted myocardium. RP SCHOLZ, TD (reprint author), NHLBI,CARDIAC ENERGET LAB,BLDG 10,ROOM 161,MAIL STOP 1061,BETHESDA,MD 20892, USA. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 34 TC 16 Z9 16 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD FEB PY 1995 VL 33 IS 2 BP 178 EP 184 DI 10.1002/mrm.1910330206 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QE692 UT WOS:A1995QE69200005 PM 7707907 ER PT J AU POSSE, S CUENOD, CA RISINGER, R LEBIHAN, D BALABAN, RS AF POSSE, S CUENOD, CA RISINGER, R LEBIHAN, D BALABAN, RS TI ANOMALOUS TRANSVERSE RELAXATION IN H-1 SPECTROSCOPY IN HUMAN BRAIN AT 4-TESLA SO MAGNETIC RESONANCE IN MEDICINE LA English DT Note DE NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; RELAXATION; DIFFUSION; PROTON SPECTROSCOPY ID MAGNETIC-RESONANCE SPECTROSCOPY; FIELD-DEPENDENCE; H-1-NMR SPECTRA; INVIVO; METABOLITES AB Longitudinal (T-1) and apparent transverse relaxation times (T-2) of choline-containing compounds (Cho), creatine/phosphocreatine (Cr/PCr), and N-acetyl aspartate (NAA) were measured in vivo in human brain at 4 Tesla. Measurements were performed using a water suppressed stimulated echo pulse sequence with complete outside volume presaturation to improve volume localization at short echo times. T-1-values of Cho (1.2 +/- 0.1 s), Cr (1.6 +/- 0.3 s), and NAA (1.6 +/- 0.2 s) at 4 Tesla in occipital brain were only slightly larger than those reported in the literature at 1.5 Tesla. Thus, TR will not adversely affect the expected enhancement of signal-to-noise at 4 Tesla. Surprisingly, apparent T-2-values of Cho (142 +/- 34 ms), or (140 +/- 13 ms), and NAA (185 +/- 24 ms) at 4 Tesla were significantly smaller than those at 1.5 Tesla and further decreased when increasing the mixing interval TM. Potential contributing factors, such as diffusion in local susceptibility related gradients, dipolar relaxation due to intracellular paramagnetic substances and motion effects are discussed. The results suggest that short echo time spectroscopy is advantageous to maintain signal to noise at 4 Tesla. C1 NIMH,WARREN GRANT MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NIMH,DIAGNOST RADIOL RES LAB,BETHESDA,MD 20892. NIMH,CLIN PHARMACOL SECT,BETHESDA,MD 20892. NHLBI,CARDIAC ENERGET LAB,BETHESDA,MD 20892. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 29 TC 64 Z9 65 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD FEB PY 1995 VL 33 IS 2 BP 246 EP 252 DI 10.1002/mrm.1910330215 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QE692 UT WOS:A1995QE69200014 PM 7707916 ER PT J AU ALLIKMETS, R GERRARD, B GLAVAC, D RAVNIKGLAVAC, M JENKINS, NA GILBERT, DJ COPELAND, NG MODI, W DEAN, M AF ALLIKMETS, R GERRARD, B GLAVAC, D RAVNIKGLAVAC, M JENKINS, NA GILBERT, DJ COPELAND, NG MODI, W DEAN, M TI CHARACTERIZATION AND MAPPING OF 3 NEW MAMMALIAN ATP-BINDING TRANSPORTER GENES FROM AN EST DATABASE SO MAMMALIAN GENOME LA English DT Article ID SEQUENCE-ANALYSIS; CYSTIC-FIBROSIS; PROGRAMS; CLONING; DNA AB Analysis of the human expressed sequence tag (EST) database identified four clones that contain sequences of previously uncharacterized genes, members of the ATP-binding cassette (ABC) superfamily. Two new ABC genes (EST20237, 31252) are located at Chromosome (Chr) 1q42 and 1q25 respectively in humans, as determined by FISH; at locations distinct from previously mapped genes of this superfamily. Two additional clones, EST 600 and EST 1596, were found to represent different ATP-binding domains of the same gene, ABC2. This gene was localized to 9q34 in humans by FISH and to the proximal region of Chr 2 in mice by linkage analysis. All genes display extensive diversity in sequence and expression pattern. We present several approaches to characterizing EST clones and demonstrate that the analysis of EST clones from different tissues is a powerful approach to identify new members of important gene families. Some drawbacks of using EST databases, including chimerism of cDNA clones, are discussed. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU NCI NIH HHS [N0-CO-74101] NR 20 TC 26 Z9 28 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD FEB PY 1995 VL 6 IS 2 BP 114 EP 117 DI 10.1007/BF00303254 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA QG121 UT WOS:A1995QG12100009 PM 7766993 ER PT J AU LUEDERS, KK AF LUEDERS, KK TI DIFFERENCES IN INTRACISTERNAL A-PARTICLE AND GLN PROVIRAL LOCI SUGGEST A GENETIC CONTRIBUTION FROM A DBA/2-LIKE STRAIN IN GENERATION OF THE C57BL/KS STRAIN SO MAMMALIAN GENOME LA English DT Note ID DIABETES-MELLITUS; ANTIGEN P73; MOUSE; MICE; INSULIN; ELEMENTS; CELLS RP LUEDERS, KK (reprint author), NCI,BIOCHEM LAB,BLDG 37,ROOM 4C-03,BETHESDA,MD 20892, USA. NR 18 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD FEB PY 1995 VL 6 IS 2 BP 134 EP 136 DI 10.1007/BF00303259 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA QG121 UT WOS:A1995QG12100014 PM 7766998 ER PT J AU ZHA, H REMMERS, EF DU, Y CASH, JM GOLDMUNTZ, EA CROFFORD, LJ WILDER, RL AF ZHA, H REMMERS, EF DU, Y CASH, JM GOLDMUNTZ, EA CROFFORD, LJ WILDER, RL TI THE RAT ATHYMIC NUDE (RNU) LOCUS IS CLOSELY LINKED TO THE INDUCIBLE NITRIC-OXIDE SYNTHASE GENE (NOS2) SO MAMMALIAN GENOME LA English DT Note ID LINKAGE; CHROMOSOME-10; MAP C1 NIAMSD,ARTHRIT & RHEUMATISM BRANCH,BETHESDA,MD 20892. RI Crofford, Leslie/J-8010-2013 NR 13 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD FEB PY 1995 VL 6 IS 2 BP 137 EP 138 DI 10.1007/BF00303260 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA QG121 UT WOS:A1995QG12100015 PM 7539310 ER PT J AU KOZAK, CA DANCIGER, M BOWES, C ADAMSON, MC PALCZEWSKI, K POLANS, AS FARBER, DB AF KOZAK, CA DANCIGER, M BOWES, C ADAMSON, MC PALCZEWSKI, K POLANS, AS FARBER, DB TI LOCALIZATION OF 3 GENES EXPRESSED IN RETINA ON MOUSE CHROMOSOME-11 SO MAMMALIAN GENOME LA English DT Note ID CYCLIC-GMP PHOSPHODIESTERASE; CANCER-ASSOCIATED RETINOPATHY; GAMMA-SUBUNIT; CGMP-PHOSPHODIESTERASE; BETA-SUBUNIT; S-MODULIN; RD MOUSE; RECOVERIN; DEGENERATION; SEQUENCE C1 UNIV CALIF LOS ANGELES,SCH MED,JULES STEIN EYE INST,LOS ANGELES,CA 90024. NIAID,BETHESDA,MD. LOYOLA MARYMOUNT UNIV,LOS ANGELES,CA. ST LOUIS UNIV,DEPT OPHTHALMOL,ST LOUIS,MO. UNIV WASHINGTON,DEPT OPHTHALMOL,SEATTLE,WA. UNIV WASHINGTON,RS DOW NEUROL SCI INST,SEATTLE,WA. UNIV WASHINGTON,DEPT PHARMACOL,SEATTLE,WA. GOOD SAMARITAN HOSP,PORTLAND,OR. FU NEI NIH HHS [EY 00331, EY 08285] NR 38 TC 9 Z9 9 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD FEB PY 1995 VL 6 IS 2 BP 142 EP 144 DI 10.1007/BF00303262 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA QG121 UT WOS:A1995QG12100017 PM 7767000 ER PT J AU KURTZ, A ZIMMER, A AF KURTZ, A ZIMMER, A TI THE MOUSE HOMOLOG OF THE HUMAN MILLER-DIEKER CHROMOSOMAL REGION (MDCR) MAPS TO MOUSE CHROMOSOME-11 IN CLOSE PROXIMITY TO MOV9 AND D11/NDS1 SO MAMMALIAN GENOME LA English DT Note ID GENETIC-MAP; LIBRARY C1 NIMH,CELL BIOL LAB,DEV BIOL UNIT,BETHESDA,MD 20892. RI Zimmer, Andreas/B-8357-2009 NR 12 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD FEB PY 1995 VL 6 IS 2 BP 145 EP 146 DI 10.1007/BF00303263 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA QG121 UT WOS:A1995QG12100018 PM 7767001 ER PT J AU BERNIER, SM UTANI, A SUGIYAMA, S DOI, T POLISTINA, C YAMADA, Y AF BERNIER, SM UTANI, A SUGIYAMA, S DOI, T POLISTINA, C YAMADA, Y TI CLONING AND EXPRESSION OF LAMININ ALPHA-2 CHAIN (M-CHAIN) IN THE MOUSE SO MATRIX BIOLOGY LA English DT Article DE EXTRACELLULAR MATRIX; LAMININ; M-CHAIN; MOUSE ID SMALL NUCLEAR RIBONUCLEOPROTEINS; BASEMENT-MEMBRANE PROTEINS; A-CHAIN; POLYADENYLATION SIGNAL; NEUROMUSCULAR-JUNCTION; BINDING GLOBULIN; SEQUENCE; MEROSIN; CELLS; INVITRO AB Laminins are a family of heterotrimeric glycoporteins specific to basement membranes. Laminin-2, consisting of alpha 2, beta 1 and gamma 1 chains, was originally identified in the basement membranes of skeletal muscle and peripheral nerve. We have isolated and sequenced the full-length cDNA for the mouse laminin alpha 2 chain. Four overlapping clones spanning 9,330 bp encode a predicted polypeptide of 3,106 amino acids having a calculated molecular mass of 390 kDa including a 23-amino-acid signal peptide. The amino acid sequence of the alpha 2 chain shares a 45.9% identity with that of the alpha 1 chain. Similar to the structure of the alpha 1 chain, the alpha 2 chain consists of several domains beginning at the N-terminus with three globular domains alternating with three epidermal growth factor-like domains followed by two alpha-helical domains and a C-terminal globular domain. The most N-terminal globular domain is highly conserved (77.3% identity) between the alpha 2 and alpha 1 chains, whereas the alpha-helical domains have low homology (30.3% identity). Northern blot and ribonuclease protection analysis revealed expression of mRNA for the alpha 2 chain in heart, kidney, liver, skin, lung and skeletal muscle of newborn mice. Such a tissue distribution suggests a role for the alpha 2 chain and, consequently, laminin-2 or -4 not only in the organization and the function of nerve and muscle tissue but possibly also in the mesenchymal components of certain tissues. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. SAITAMA MED SCH,DEPT NEUROSURG,MOROYAMA,SAITAMA,JAPAN. KYOTO UNIV,DEPT GERIATR MED,KYOTO,JAPAN. UNIV NAPLES,DEPT CELLULAR & MOLEC BIOL & PATHOL,NAPLES,ITALY. NR 38 TC 54 Z9 55 U1 0 U2 2 PU GUSTAV FISCHER VERLAG PI STUTTGART PA WOLLGRASWEG 49 POSTFACH 72 01 43, D-70577 STUTTGART, GERMANY SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD FEB PY 1995 VL 14 IS 6 BP 447 EP 455 DI 10.1016/0945-053X(95)90002-0 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QJ176 UT WOS:A1995QJ17600002 PM 7795883 ER PT J AU CVEKL, A KASHANCHI, F SAX, CM BRADY, JN PIATIGORSKY, J AF CVEKL, A KASHANCHI, F SAX, CM BRADY, JN PIATIGORSKY, J TI TRANSCRIPTIONAL REGULATION OF THE MOUSE ALPHA-A-CRYSTALLIN GENE - ACTIVATION-DEPENDENT ON A CYCLIC AMP-RESPONSIVE ELEMENT (DE1/CRE) AND A PAX-6-BINDING SITE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TISSUE-SPECIFIC EXPRESSION; LENS-SPECIFIC EXPRESSION; HOMEOBOX-CONTAINING GENE; RAT SOMATOSTATIN GENE; HEAT-SHOCK PROTEIN; TRANSGENIC MICE; DNA-BINDING; B-CRYSTALLIN; PREINITIATION COMPLEX; EPITHELIAL-CELLS AB Two cis-acting promoter elements (-108 to -100 and -49 to -33) of the mouse alpha A-crystallin gene, which is highly expressed in the ocular lens, were studied. Here we show that DE1 (-108 to -100; 5'TGACGGTG3'), which resembles the consensus cyclic AMP (cAMP)-responsive element sequence (CRE; 5'TGACGT[AIC] [A/G]3'), behaves like a functional CRE site. Transfection experiments and electrophoretic mobility shift assays (EMSAs) using site-specific mutations correlated a loss of function with deviations from the CRE consensus sequence. Results of EMSAs in the presence of antisera against CREE, Delta CREB, and CREM were consistent with the binding of CREB-like proteins to the DE1 sequence. Stimulation of alpha A-crystallin promoter activity via 8-bromo-cAMP, forskolin, or human T-cell leukemia virus type I Tax(1) in transfections and reduction of activity of this site in cell-free transcription tests by competition with the somatostatin CRE supported the idea that DEI is a functional CRE. Finally, Pax-6, a member of the paired-box family of transcription factors, activated the mouse alpha A-crystallin promoter in cotransfected COP-8 fibroblasts and bound to the -59 to -29 promoter sequence in EMSAs. These data provide evidence for a synergistic role of Pax-6 and CREB-like proteins for high expression of the mouse alpha A-crystallin gene in the lens. C1 NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892. NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. RI Cvekl, Ales/B-2427-2013 NR 80 TC 103 Z9 103 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1995 VL 15 IS 2 BP 653 EP 660 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QC385 UT WOS:A1995QC38500007 PM 7823934 ER PT J AU ERNST, MK DUNN, LL RICE, NR AF ERNST, MK DUNN, LL RICE, NR TI THE PEST-LIKE SEQUENCE OF I-KAPPA-B-ALPHA IS RESPONSIBLE FOR INHIBITION OF DNA-BINDING BUT NOT FOR CYTOPLASMIC RETENTION OF C-REL OR RELA HOMODIMERS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NUCLEAR-LOCALIZATION SIGNAL; TRANSCRIPTION FACTOR; ANKYRIN REPEATS; P50 SUBUNIT; P65 SUBUNIT; PROTEINS; ACTIVATION; PRECURSOR; P105; PHOSPHORYLATION AB In most cells, proteins belonging to the Rel/NF-kappa B family of transcription factors are held in inactive form in the cytoplasm by an inhibitor protein, I kappa B alpha. Stimulation of the cells leads to degradation of the inhibitor and transit of active DNA-binding Rel/NF-kappa B dimers to the nucleus. I kappa B alpha is also able to inhibit DNA binding by Rel/NF-kappa B dimers in vitro, suggesting that it may perform the same function in cells when the activating signal is no longer present. Structurally, the human I kappa B alpha molecule can be divided into three sections: a 70-amino-acid N terminus with no known function, a 205-residue midsection composed of six ankyrin-like repeats, and a very acidic 42-amino-acid C terminus that resembles a PEST sequence. In this study we examined how the structural elements of the I kappa B alpha protein correlate,vith its functional capabilities both in vitro and in vivo. Using a battery of I kappa B alpha mutants, we show that (i) a dimer binds a single I kappa B alpha molecule, (ii) the acidic C-terminal region of I kappa B alpha is not required for protein-protein binding and does not mask the nuclear localization signal of the dimer, (iii) the same C-terminal region is required for inhibition of DNA binding, and (iv) this inhibition may be accomplished by direct interaction between the PEST-like region and the DNA-binding region of one of the subunits of the dimer. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC VIROL & CARCINOGENESIS LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 55 TC 103 Z9 105 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1995 VL 15 IS 2 BP 872 EP 882 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QC385 UT WOS:A1995QC38500029 PM 7823953 ER PT J AU FLEISCHMAN, LF HOLTZCLAW, L RUSSELL, JT MAVROTHALASSITIS, G FISHER, RJ AF FLEISCHMAN, LF HOLTZCLAW, L RUSSELL, JT MAVROTHALASSITIS, G FISHER, RJ TI ETS-1 IN ASTROCYTES - EXPRESSION AND TRANSMITTER-EVOKED PHOSPHORYLATION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID LONG TERMINAL REPEAT; TRANSCRIPTIONAL ACTIVATION; PROTO-ONCOGENES; CALCIUM WAVES; C-FOS; CELLS; GENE; KINASE; PROTOONCOGENE; SEQUENCE AB The ets-1 protein has been primarily studied as a sequence-specific transcriptional regulator that is predominately expressed in lymphoid cells. In this report, we show that ets-1 is also expressed in astrocytes and astrocytoma cells and is regulated during both signal transduction and differentiation. Both isoforms of ets-1, p51 and p42, were found in astrocytes and astrocytoma cells, but whereas expression of p51 was strong, p42, the alternate splice product previously shown to lack the phosphorylation domain, was difficult to detect and was present at a level 10- to 40-fold lower than that of p51. This differed by roughly an order of magnitude from the ratio generally observable in T cells and thymocytes. In two astrocytoma lines of human origin, CCF and 1321N1, ets-1 phosphorylation was stimulated by bradykinin and carbachol, respectively. Glutamate, norepinephrine, and bradykinin elicited phosphorylation of p51 in cultures of primary rat type 1 astrocytes. ets-1 phosphorylation was dramatically blocked by KT5926, an inhibitor of myosin light-chain kinase, suggesting that this kinase may be involved in phosphorylation of ets-1 in vivo. Investigations of retinoic acid-induced differentiation in P19 cells provided further support for a strong correlation of ets-1 with the pathway for astrocyte differentiation. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,CELLULAR BIOCHEM LAB,FREDERICK,MD 21702. NICHHD,MOLEC & CELLULAR NEUROPHYSIOL LAB,BETHESDA,MD 20892. RP FLEISCHMAN, LF (reprint author), NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702, USA. RI Fisher, Robert/B-1431-2009 NR 58 TC 33 Z9 33 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1995 VL 15 IS 2 BP 925 EP 931 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QC385 UT WOS:A1995QC38500034 PM 7823957 ER PT J AU WILLEMSEN, R TYBULEWICZ, V SIDRANSKY, E ELIASON, WK MARTIN, BM LAMARCA, ME REUSER, AJJ TREMBLAY, M WESTPHAL, H MULLIGAN, RC GINNS, EI AF WILLEMSEN, R TYBULEWICZ, V SIDRANSKY, E ELIASON, WK MARTIN, BM LAMARCA, ME REUSER, AJJ TREMBLAY, M WESTPHAL, H MULLIGAN, RC GINNS, EI TI A BIOCHEMICAL AND ULTRASTRUCTURAL EVALUATION OF THE TYPE-2 GAUCHER MOUSE SO MOLECULAR AND CHEMICAL NEUROPATHOLOGY LA English DT Article DE TYPE 2 GAUCHER MICE; TARGETED DISRUPTION; GLUCOCEREBROSIDASE; GLUCOCEREBROSIDE; LYSOSOMES; MICROGLIA; NEURONS ID GLUCOCEREBROSIDASE GENE; TARGETED DISRUPTION; CELL-FUNCTION; DISEASE; MODEL AB Gaucher mice, created by targeted disruption of the glucocerebrosidase gene, are totally deficient in glucocerebrosidase and have a rapidly deteriorating clinical course analogous to the most severely affected type 2 human patients. An ultrastructural study of tissues from these mice revealed glucocerebroside accumulation in bone marrow, liver, spleen, and brain. This glycolipid had a characteristic elongated tubular structure and was contained in lysosomes, as demonstrated by colocalization with both ingested carbon particles and cathepsin D. In the central nervous system (CNS), glucocerebroside was diffusely stored in microglia cells and in brainstem and spinal cord neurons, but not in neurons of the cerebellum or cerebral cortex. This rostral-caudal pattern of neuronal lipid storage in these Gaucher mice replicates the pattern seen in type 2 human Gaucher patients and clearly demonstrates that glycosphingolipid catabolism and/or accumulation varies within different brain regions. Surprisingly, the cellular pathology of tissue from these Gaucher mice was relatively mild, and suggests that the early and rapid demise of both Gaucher mice and severely affected type 2 human neonates may be the result of both a neurotoxic metabolite, such as glucosylsphingosine, and other factors, such as skin water barrier dysfunction secondary to the absence of glucocerebrosidase activity. C1 NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. ERASMUS UNIV ROTTERDAM,DEPT CELL BIOL & GENET,3000 DR ROTTERDAM,NETHERLANDS. NIMR,MRC,LONDON,ENGLAND. NICHHD,BETHESDA,MD 20892. MCGILL UNIV,MONTREAL,PQ,CANADA. WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. NR 24 TC 18 Z9 18 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07012 SN 1044-7393 J9 MOL CHEM NEUROPATHOL JI Mol. Chem. Neuropathol. PD FEB-APR PY 1995 VL 24 IS 2-3 BP 179 EP 192 DI 10.1007/BF02962142 PG 14 WC Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA QX448 UT WOS:A1995QX44800007 PM 7632321 ER PT J AU SMITH, MA RICHEY, PL KUTTY, RK WIGGERT, B PERRY, G AF SMITH, MA RICHEY, PL KUTTY, RK WIGGERT, B PERRY, G TI ULTRASTRUCTURAL-LOCALIZATION OF HEME OXYGENASE-1 TO THE NEUROFIBRILLARY PATHOLOGY OF ALZHEIMER-DISEASE SO MOLECULAR AND CHEMICAL NEUROPATHOLOGY LA English DT Article; Proceedings Paper CT Meeting on Neurodegenerative Disorders - Common Molecular Mechanisms CY APR 10-15, 1994 CL OCHO RIOS, JAMAICA DE ALZHEIMER DISEASE; FREE RADICALS; AGING; SENILE DEMENTIA; HEME OXYGENASE-1; NEUROFIBRILLARY PATHOLOGY C1 NEI,BETHESDA,MD 20892. RP SMITH, MA (reprint author), CASE WESTERN RESERVE UNIV,INST PATHOL,2085 ADELBERT RD,CLEVELAND,OH 44106, USA. RI Smith, Mark/A-9053-2009; Perry, George/A-8611-2009 OI Perry, George/0000-0002-6547-0172 NR 8 TC 12 Z9 12 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07012 SN 1044-7393 J9 MOL CHEM NEUROPATHOL JI Mol. Chem. Neuropathol. PD FEB-APR PY 1995 VL 24 IS 2-3 BP 227 EP 230 DI 10.1007/BF02962147 PG 4 WC Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA QX448 UT WOS:A1995QX44800012 PM 7632324 ER PT J AU SCHULZ, NT PAULHIAC, CI LEE, L ZHOU, RP AF SCHULZ, NT PAULHIAC, CI LEE, L ZHOU, RP TI ISOLATION AND EXPRESSION ANALYSIS OF TYRO3, A MURINE GROWTH-FACTOR RECEPTOR TYROSINE KINASE PREFERENTIALLY EXPRESSED IN ADULT BRAIN SO MOLECULAR BRAIN RESEARCH LA English DT Article DE NEUROTROPHIC FACTOR; IN SITU HYBRIDIZATION; CEREBRAL CORTEX; HIPPOCAMPUS; CEREBELLUM ID CENTRAL-NERVOUS-SYSTEM; NEURAL CREST CELLS; NEUROTROPHIC FACTOR; HIPPOCAMPAL-NEURONS; MOLECULAR-CLONING; FACTOR PREVENTS; FAMILY; DEATH; CULTURE; DIFFERENTIATION AB Growth factors and their receptors function in the nervous system to induce proliferation and differentiation of neuronal precursor cells and to support survival of mature neurons. We have isolated a murine growth factor receptor tyrosine kinase using an anti-phosphotyrosine antibody screening procedure and studied the pattern of expression. The deduced amino acid sequence of the kinase has all the characteristics of a growth factor receptor and consists of a putative extracellular domain, a transmembrane domain, and a tyrosine kinase domain. Sequence comparison with known receptor tyrosine kinases indicated that the murine kinase is a mouse homolog of tyro3, tyro3 belongs to the Axd/Ufo growth factor receptor family. In the putative extracellular domain, there are two Ig-like domains and two fibronectin type III repeats which are conserved in other members of the Axl/Ufo family receptors. Northern blot hybridization analysis showed that tyro3 is expressed at high levels in the brain of adult mice, although considerable expression was also observed in the testis. In situ hybridization analysis revealed that high levels of tyro3 are expressed in the cerebral cortex, the lateral septum, the hippocampus, the olfactory bulb, and in the cerebellum. The highest levels of tyro3 expression in the brain are associated with neurons. The preferential expression of tyro3 in specific regions of the adult mouse brain suggests that tyro3 may function as a novel neurotrophic factor receptor. C1 RUTGERS STATE UNIV,COLL PHARM,CANC RES LAB,PISCATAWAY,NJ 08855. PROGRAM RESOURCES INC,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NR 42 TC 19 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD FEB PY 1995 VL 28 IS 2 BP 273 EP 280 DI 10.1016/0169-328X(94)00216-2 PG 8 WC Neurosciences SC Neurosciences & Neurology GA QE617 UT WOS:A1995QE61700011 ER PT J AU HUDSONTAYLOR, DE DOLAN, SA KLOTZ, FW FUJIOKA, H AIKAWA, M KOONIN, EV MILLER, LH AF HUDSONTAYLOR, DE DOLAN, SA KLOTZ, FW FUJIOKA, H AIKAWA, M KOONIN, EV MILLER, LH TI PLASMODIUM-FALCIPARUM PROTEIN ASSOCIATED WITH THE INVASION JUNCTION CONTAINS A CONSERVED OXIDOREDUCTASE DOMAIN SO MOLECULAR MICROBIOLOGY LA English DT Article ID ALKYL HYDROPEROXIDE REDUCTASE; HUMAN MALARIA PARASITES; NUCLEOTIDE-SEQUENCE; IMMUNOELECTRON MICROSCOPY; SALMONELLA-TYPHIMURIUM; SECONDARY STRUCTURE; ESCHERICHIA-COLI; MOVING JUNCTION; SURFACE PROTEIN; GENE AB The merozoite cap Protein-1 (MCP-1) of Plasmodium falciparum follows the distribution of the moving junction during invasion of erythrocytes. We have cloned the gene encoding this protein from a cDNA library using a monoclonal antibody, The protein lacks a signal sequence and has no predicted transmembrane domains; none of the antisera reacts with the surfaces of intact merozoites, indicating that the cap distribution is submembranous. MCP-1 is divided into three domains. The N-terminal domain includes a 52-amino-acid region that is highly conserved in a large family of bacterial and eukaryotic proteins. Based on the known functions of two proteins of this family and the pattern of amino acid conservation, it is predicted that this domain may possess oxidereductase activity, since the active cysteine residue of this domain is invariant in all proteins of the family. The other two domains of MCP-1 are not found in any other members of this protein family and may reflect the specific function of MCP-1 in invasion, The middle domain is negatively charged and enriched in glutamate; the C-terminal domain is positively charged and enriched in lysine, By virtue of its positive charge, the C-terminal domain resembles domains in some cytoskeleton-associated proteins and may mediate the interaction of MCP-1 with cytoskeleton in Plasmodium. C1 NIAID,MALARIA RES LAB,BETHESDA,MD 20892. WALTER REED ARMY MED CTR,DEPT IMMUNOL,WASHINGTON,DC 20307. CASE WESTERN RESERVE UNIV,INST PATHOL,CLEVELAND,OH 44106. NIH,NATL LIB MED,DIV NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20892. NR 54 TC 16 Z9 17 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD FEB PY 1995 VL 15 IS 3 BP 463 EP 471 DI 10.1111/j.1365-2958.1995.tb02260.x PG 9 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA QH529 UT WOS:A1995QH52900009 PM 7783617 ER PT J AU ROCKEY, DD HEINZEN, RA HACKSTADT, T AF ROCKEY, DD HEINZEN, RA HACKSTADT, T TI CLONING AND CHARACTERIZATION OF A CHLAMYDIA-PSITTACI GENE CODING FOR A PROTEIN LOCALIZED IN THE INCLUSION MEMBRANE OF INFECTED-CELLS SO MOLECULAR MICROBIOLOGY LA English DT Article ID TOXOPLASMA-GONDII; PHAGOLYSOSOME FUSION; HOST-CELL; TRACHOMATIS; PURIFICATION; ASSOCIATION; INHIBITION; NUCLEOTIDE; ENVELOPES; TRANSPORT AB Chlamydiae are obligate intracellular bacteria which occupy a non-acidified vacuole (the inclusion) throughout their developmental cycle. Little is known about events leading to the establishment and maintenance of the chlamydial inclusion membrane. To identify chlamydial proteins which are unique to the intracellular phase of the life cycle, an expression library of Chlamydia psiffaci DNA was screened with convalescent antisera from infected animals and hyperimmune antisera generated against formalin-killed purified chlamydiae. Overlapping genomic clones were identified which expressed a 39 kDa protein only recognized by the convalescent sera. Sequence analysis of the clones identified two open reading frames (ORFs), one of which (ORF1) coded for a predicted 39 kDa gene product. The ORF1 sequence was amplified and fused to the malE gene of Escherichia coli and antisera were raised against the resulting fusion protein. Immunoblotting with these antisera demonstrated that the 39 kDa protein was present in lysates of infected cells and in reticulate bodies (RBs), but was at the limit of detection in lysates of purified C. psiffaci elementary bodies. Fluorescence microscopy experiments demonstrated that this protein was localized in the inclusion membrane of infected HeLa cells, but was not detected on the developmental forms within the inclusion. Because the protein produced by ORF1 is deposited on the inclusion membrane of infected cells, this gene has been designated incA, (inclusion membrane protein A) and its gene product, IncA. In addition to the inclusion membrane, these antisera labelled structures that extended from the inclusion over the nucleus or into the cytoplasm of infected cells. Immunoblotting also demonstrated that IncA, in lysates of infected cells, had a migration pattern that seemed indicative of post-translational modification, This pattern was not observed in immunoblots of RBs or in the E. coli expressing IncA. Collectively, these data identify a chlamydial gene which codes for a protein that is released from RB and is localized in the inclusion membrane of infected cells. RP ROCKEY, DD (reprint author), NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,HAMILTON,MT 59840, USA. NR 28 TC 132 Z9 135 U1 1 U2 4 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD FEB PY 1995 VL 15 IS 4 BP 617 EP 626 DI 10.1111/j.1365-2958.1995.tb02371.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA QL549 UT WOS:A1995QL54900004 PM 7783634 ER PT J AU MARCHAMEGADZIE, R HINTON, DM AF MARCHAMEGADZIE, R HINTON, DM TI THE BACTERIOPHAGE-T4 MIDDLE PROMOTER P-UVSX - ANALYSIS OF REGIONS IMPORTANT FOR BINDING OF THE T4 TRANSCRIPTIONAL ACTIVATOR MOTA AND FOR ACTIVATION OF TRANSCRIPTION SO MOLECULAR MICROBIOLOGY LA English DT Article ID COLI RNA-POLYMERASE; PROTEIN-DNA INTERACTIONS; POTASSIUM GLUTAMATE; EXPRESSED PROTEIN; CRYSTAL-STRUCTURE; SIGMA-70 SUBUNIT; ALPHA-SUBUNIT; INVITRO; RECOGNITION; MUTANT AB Bacteriophage T4 middle promoters, which are transcribed using phage-modified host RNA polymerase and the T4 transcriptional activator, MotA, match the host sigma(70) consensus sequence at -10, but they have a different consensus ((t/a)(t/a)TGCTT(t/c)A) (a MotA box) at -30. While the T4 middle promoter P-uvsX has these -10 and -30 motifs, it also has matches to the MotA box at -35, -51, -70, and -87. We show that MotA binds to P-uvsX DNA, footprinting a region that includes the MotA boxes at -30, -35, and -51. Very high levels of MotA are required for footprinting and gel-shift experiments, and protein-DNA complexes formed in the presence of both phage-modified polymerase and MotA are more resistant to HindIII cleavage than those formed with either protein alone. These results suggest that MotA-DNA interactions may be stabilized by phage-modified polymerase. Sequences between -18 and -38 are absolutely required for MotA activation of transcription, but sequences upstream of -38 are stimulatory, particularly when chloride instead of glutamate is the major anion. Our results dissect P-uvsX into a core promoter, downstream of -38, which is required for MotA activation, and an upstream region that enhances transcription especially under conditions less favourable for protein-DNA interactions. C1 NIDDKD,MOLEC & CELLULAR BIOL LAB,BETHESDA,MD 20892. NR 39 TC 30 Z9 30 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD FEB PY 1995 VL 15 IS 4 BP 649 EP 660 DI 10.1111/j.1365-2958.1995.tb02374.x PG 12 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA QL549 UT WOS:A1995QL54900007 PM 7783637 ER PT J AU YAN, GM LIN, SZ IRWIN, RP PAUL, SM AF YAN, GM LIN, SZ IRWIN, RP PAUL, SM TI ACTIVATION OF MUSCARINIC CHOLINERGIC RECEPTORS BLOCKS APOPTOSIS OF CULTURED CEREBELLAR GRANULE NEURONS SO MOLECULAR PHARMACOLOGY LA English DT Article ID D-ASPARTATE RECEPTOR; NERVOUS-SYSTEM; CELL-DEATH; RAT; SURVIVAL; MOTONEURONS; GLUTAMATE; PROTEIN; CORTEX; LAYER AB We have recently reported that the majority of cultured rat cerebellar granule neurons undergo apoptosis when maintained in the presence of physiological concentrations of K+ (nondepolarizing conditions). We now report that exposure of cultured cerebellar granule neurons, maintained under nondepolarizing conditions, to the muscarinic cholinergic receptor (mAchR) agonists carbachol and muscarine results in a concentration- and time-dependent inhibition of apoptosis. The nicotinic cholinergic receptor agonist (-)-nicotine fails to mimic, and the nicotinic cholinergic receptor antagonist dihydro-beta-erythroidine fails to antagonize, the survival-promoting effects of carbachol. In contrast, relatively low concentrations of atropine completely prevent the effects of carbachol in blocking apoptotic death of cultured granule neurons. Although the m1- and m2-preferring mAchR antagonists pirenzepine and gallamine, respectively, fail to reverse the effects of carbachol, the m3-preferring antagonist 4-diphenylacetoxyl-N-methylpiperidine methiodide completely blocks the survival-promoting effects of carbachol. These data demonstrate that activation of the mAchR (possibly of the m3 subtype) blocks apoptosis of cultured cerebellar granule neurons. The antiapoptotic effects of mAchR agonists are not indirectly mediated via glutamate release from granule neurons, because antagonists of either N-methyl-D-aspartate or non-N-methyl-D-aspartate glutamate receptors fail to affect the antiapoptotic effects of carbachol or muscarine. Moreover, exposure of cultured cerebellar granule neurons to antiapoptotic concentrations of carbachol, in contrast to high concentrations of K+ or glutamate receptor agonists, results in only a small and transient elevation of the intracellular Ca2+ concentration, as measured by fura-2 microfluorimetry. Slow neurotransmitters such as acetylcholine, acting via their cognate G protein-coupled receptors, may prevent neuronal apoptosis in the developing (and perhaps adult) central nervous system. C1 ELI LILLY & CO,LILLY CORP CTR,LILLY RES LABS,INDIANAPOLIS,IN 46285. NIMH,CLIN NEUROSCI BRANCH,MOLEC PHARMACOL SECT,BETHESDA,MD 20892. INDIANA UNIV,SCH MED,DEPT PHARMACOL & TOXICOL,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,DEPT MED,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,DEPT PSYCHIAT,INDIANAPOLIS,IN 46202. NR 38 TC 97 Z9 115 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD FEB PY 1995 VL 47 IS 2 BP 248 EP 257 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QJ042 UT WOS:A1995QJ04200006 PM 7870032 ER PT J AU SZALLASI, Z KOSA, K SMITH, CB DLUGOSZ, AA WILLIAMS, EK YUSPA, SH BLUMBERG, PM AF SZALLASI, Z KOSA, K SMITH, CB DLUGOSZ, AA WILLIAMS, EK YUSPA, SH BLUMBERG, PM TI DIFFERENTIAL REGULATION BY ANTI-TUMOR-PROMOTING 12-DEOXYPHORBOL-13-PHENYLACETATE REVEALS DISTINCT ROLES OF THE CLASSICAL AND NOVEL PROTEIN-KINASE-C ISOZYMES IN BIOLOGICAL RESPONSES OF PRIMARY MOUSE KERATINOCYTES SO MOLECULAR PHARMACOLOGY LA English DT Article ID NONPROMOTING 12-DEOXYPHORBOL 13-ESTERS; RBL-2H3 CELLS; EPSILON; INVITRO; SKIN; BRYOSTATIN-1; SPECIFICITY; EXOCYTOSIS; INHIBITION; ACTIVATOR AB 12-Deoxyphorbol-13-phenylacetate (dPP) is the prototype for a new class of phorbol derivatives that function as protein kinase C (PKC) activators with potent anti-tumor-promoting activity. To explore the mechanism of action of dPP, we have conducted detailed analyses of the translocation and down-regulation patterns of individual PKC isozymes in mouse primary keratinocytes upon dPP treatment. PKC-alpha, -delta, and -epsilon were very quickly (within 2-5 min) translocated from the soluble fraction to the Triton X-100-soluble particulate fraction. PKC-delta and -epsilon were translocated with 2 orders of magnitude higher potency than was PKC-alpha. After translocation, PKC-alpha, -delta, -eta, and -epsilon were down-regulated; the down-regulation of PKC-E contrasts with its retention after phorbol-12-myristate-13-acetate or bryostatin treatment. As was the case with translocation, dPP down-regulated the novel PKC isozymes (delta, epsilon, and eta) with 2 orders of magnitude higher potency (ED(50), about 1-2 nM), compared with PKC-alpha (ED(50), about 100 nM). dPP induced transglutaminase activity, ornithine decarboxylase activity, and cornification with potencies similar to that for PKC-alpha translocation. On the other hand, dPP caused inhibition of EGF binding with a potency similar to that for the translocation of the novel PKC isozymes. Although the generality of its selectivity in different cell types remains to be determined, at least in keratinocytes dPP is a powerful tool for dissecting the involvement of the classical and novel PKC isozymes in biological responses. The unique regulatory pattern of PKC-epsilon could contribute to the anti-tumor-promoting activity of dPP. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. OI Kosa, Karolina/0000-0001-7867-2403 NR 32 TC 24 Z9 24 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD FEB PY 1995 VL 47 IS 2 BP 258 EP 265 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QJ042 UT WOS:A1995QJ04200007 PM 7870033 ER PT J AU XIAO, RP JI, XW LAKATTA, EG AF XIAO, RP JI, XW LAKATTA, EG TI FUNCTIONAL COUPLING OF THE BETA(2)-ADRENOCEPTOR TO A PERTUSSIS-TOXIN-SENSITIVE G-PROTEIN IN CARDIAC MYOCYTES SO MOLECULAR PHARMACOLOGY LA English DT Article ID BETA-ADRENERGIC-RECEPTOR; HUMAN BETA-2-ADRENERGIC RECEPTOR; HUMAN VENTRICULAR MYOCARDIUM; CONGESTIVE-HEART-FAILURE; FAILING HUMAN HEARTS; ADENYLATE-CYCLASE; SARCOPLASMIC-RETICULUM; STRUCTURAL BASIS; CELLS; STIMULATION AB Recently we demonstrated that the effects of beta(2)-adrenoceptor (AR) stimulation to augment Ca2+ current (I-Ca), cytosolic Ca2+ (Ca-i) transients, and contractility in rat ventricular myocytes are largely dissociated from its effect to increase cellular cAMP levels. This result suggested that beta(2)ARs might be coupled to signaling pathways other than the G(s alpha)-mediated activation of adenylyl cyclase. Here we show that pertussis toxin (PTX) pretreatment specifically potentiates the responses of rat heart cells to beta(2)AR but not beta(1)AR stimulation. After PTX pretreatment, 1)the dose-response curve for the effects of the beta(2)AR agonist zinterol on contraction amplitude is shifted leftward and upward (EC(50) changed from about 1.0 mu M to 70 nM), 2) in indo-1-loaded cells, the maximal effects of zinterol (10(-5) M) on Ca-i transient and contraction amplitudes are additionally increased 1.7- and 2.0-fold, respectively, over those in control cells, and 3) the increase in I-Ca amplitude induced by the same zinterol concentration is potentiated by 2.5-fold. Similar effects of PTX are observed when beta(2)ARs are stimulated by isoproterenol in the presence of a selective beta(1)AR blocker, CGP 20712A. All effects of beta(2)AR agonists in both PTX-treated and control cells are abolished by a selective beta(2)AR blocker, ICI 118,551. In contrast, neither the base-line I-Ca, Ca-i transient, and contraction in the absence of beta AR stimulation nor the beta(1)AR-mediated augmentations of these parameters are significantly altered by PTX treatment. These results demonstrate, for the first time, that the G(s)-coupled beta(2)AR can simultaneously activate a pathway that leads to functional inhibition in cardiac cells via a PTX-sensitive G protein. The activation of more than one G protein during beta(2)AR stimulation, leading to functionally opposite effects, may provide a mechanism to protect the heart from Ca2+ overload and arrthythmias during the response to stress. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. NR 48 TC 277 Z9 286 U1 0 U2 6 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD FEB PY 1995 VL 47 IS 2 BP 322 EP 329 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QJ042 UT WOS:A1995QJ04200015 PM 7870040 ER PT J AU HARRIS, BD WONG, G MOODY, EJ SKOLNICK, P AF HARRIS, BD WONG, G MOODY, EJ SKOLNICK, P TI DIFFERENT SUBUNIT REQUIREMENTS FOR VOLATILE AND NONVOLATILE ANESTHETICS AT GAMMA-AMINOBUTYRIC-ACID TYPE-A RECEPTORS SO MOLECULAR PHARMACOLOGY LA English DT Article ID GABA-A RECEPTORS; CHLORIDE CHANNEL COMPLEX; BENZODIAZEPINE RECEPTORS; RAT-BRAIN; NEUROCHEMICAL ACTIONS; STEROID MODULATION; RESPONSES; NEUROSTEROIDS; HETEROGENEITY; POTENTIATION AB The ability of volatile (halothane and isoflurane) and nonvolatile (alphaxalone and pentobarbital) general anesthetics to modulate radioligand binding to gamma-aminobutyric acid (GABA)(A) receptors was examined in an immortalized cell line (WSS-1) expressing rat alpha 1 and gamma 2 subunits. Volatile anesthetics enhance [H-3]flunitrazepam binding to WSS-1 cells in a concentration-dependent manner, with potencies and efficacies comparable to those found with native GABA(A) receptors. Transfection of these cells with cDNAs encoding rat beta 2 or beta 3 subunits had a significant influence on anesthetic efficacy but not potency in this assay. Thus, transfection with the beta 2 subunit reduced the efficacy of both isoflurane and halothane, whereas transfection with the beta 3 subunit increased the efficacy of isoflurane but not halothane, compared with values obtained in WSS-1 cells. In contrast, alphaxalone (an anesthetic steroid) had no effect, whereas at high concentrations pentobarbital (an anesthetic barbiturate) produced a modest inhibition of [H-3]flunitrazepam binding to GABAA receptors in WSS-1 cells. Transfection of WSS-1 cells with cDNAs encoding either beta 2 or beta 3 subunits resulted in a concentration-dependent enhancement of [H-3]flunitrazepam binding by these nonvolatile anesthetics. Moreover, pentobarbital was significantly more potent in enhancing [H-3]flunitrazepam binding to WSS-1 cells transfected with the beta 2 subunit, compared with the beta 3 subunit. The difference in subunit requirements between volatile and nonvolatile anesthetics for enhancement of [H-3]-flunitrazepam binding indicates that these classes of agents affect GABA(A) receptor function at distinct loci. These studies also provide evidence that the beta subunit is required for these nonvolatile anesthetics to positively modulate GABA(A) receptors. C1 NIDDKD,NEUROSCI LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV HOSP,DEPT ANESTHESIOL & CRIT CARE MED,DIV CARDIAC,BALTIMORE,MD 21287. NR 41 TC 49 Z9 49 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD FEB PY 1995 VL 47 IS 2 BP 363 EP 367 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QJ042 UT WOS:A1995QJ04200020 PM 7870045 ER PT J AU POLING, JS KARANIAN, JW SALEM, N VICINI, S AF POLING, JS KARANIAN, JW SALEM, N VICINI, S TI TIME-DEPENDENT AND VOLTAGE-DEPENDENT BLOCK OF DELAYED RECTIFIER POTASSIUM CHANNELS BY DOCOSAHEXAENOIC ACID SO MOLECULAR PHARMACOLOGY LA English DT Article ID POLYUNSATURATED FATTY-ACIDS; TRANSIENT OUTWARD CURRENT; ARACHIDONIC-ACID; DIVALENT-CATIONS; SMOOTH-MUSCLE; NEURONS; CELLS; MODULATION; MECHANISM AB Docosahexaenoic acid (22:6n3) acts at an extracellular site to produce a voltage- and time-dependent block of the delayed rectifier current (I-K) similar to that classically described for intracellularly applied quaternary ammonia compounds. In dissociated cells from the pineal gland, some long-chain polyunsaturated fatty acids reduced both late sustained (I-K) (for 22:6n3, IC50 = 2.5 +/- 0.3 mu M) and early transient (I-A) (IC50 = 2.0 +/- 0.1 mu M) components of potassium current when applied extracellularly, whereas the monounsaturate oleic acid had minimal efficacy, From comparisons of other related fatty acids, it was determined that there is a structural requirement for polyunsaturation to block I-K. In contrast, chain-elongated 22-carbon polyunsaturates acted similarly to their precursor 20-carbon fatty acids (arachidonic acid and eicosapentanoic acid), Block of I-K by 22:6n3 was accompanied by a dose-dependent acceleration of the current decay in both whole-cell and outside-out membrane patches, and 22:6n3 increased the macroscopic inactivation rate of I-A. The combined ''eicosanoid'' inhibitor eicosatetraenoic acid, when included in the patch pipette, did not antagonize the action of 22:6n3. Instead, eicosatetraenoic acid produced a direct block of I-K when applied extracellularly at high concentrations (25 mu M). Analyses of voltage- and time-dependent block by 22:6n3 support the hypothesis that certain fatty acids directly interact with and preferentially block the open state of some potassium channels. We also describe an interaction between fatty acid block and zinc; 22:6n3 failed to block either I-A or I-K in the presence of zinc or cadmium, whereas extracellular calcium did not affect the response. These studies suggest a possible biological function for 22:6n3 in the nervous system, which may underlie its essential role during neural development. C1 GEORGETOWN UNIV,MED CTR,SCH MED,DEPT PHYSIOL & BIOPHYS,WASHINGTON,DC 20007. NIAAA,DIV INTRAMURAL CLIN & BIOL RES,MEMBRANE BIOCHEM & BIOPHYS LAB,ROCKVILLE,MD 20852. NR 37 TC 48 Z9 52 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD FEB PY 1995 VL 47 IS 2 BP 381 EP 390 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QJ042 UT WOS:A1995QJ04200023 PM 7870048 ER PT J AU WYROBEK, A LOWE, X PINKEL, D BISHOP, J AF WYROBEK, A LOWE, X PINKEL, D BISHOP, J TI ANEUPLOIDY IN LATE-STEP SPERMATIDS OF MICE DETECTED BY 2-CHROMOSOME FLUORESCENCE IN-SITU HYBRIDIZATION SO MOLECULAR REPRODUCTION AND DEVELOPMENT LA English DT Article DE MURINE; SPERMATIDS; ANEUPLOIDY; DNA PROBES; FLUORESCENCE IN SITU HYBRIDIZATION (FISH) ID EMBRYOS FERTILIZED INVITRO; MOUSE SPERMATOCYTES; INDUCTION; CELLS; GERM; DROSOPHILA; FREQUENCY; INVIVO; NTA AB A multicolor procedure employing fluorescence in situ hybridization is described for detecting chromosomal domains and germinal aneuploidy in late-step spermatids in mice using DNA probes specific for repetitive sequences near the centromeres of chromosomes 8 and X. These probes were nick-translated with biotin- or digoxigenin-labeled nucleotides, and were detected with FITC or rhodamine. Probe and hybridization specificities were confirmed using metaphase chromosomes from spleen and bone marrow cells as well as from primary and secondary spermatocytes. Late-step spermatids, identified in testicular preparations by their hooked shape, yielded compact fluorescence domains in similar to 50% and >99% of cells when hybridized with probes for chromosomes X and 8, respectively. In a survey of >80,000 late-step spermatids from 8 healthy young adult C57BL/6 or B6C3F1 mice, similar to 3/10,000 spermatids had fluorescence phenotypes indicative of X-X or 8-8 hyperhaploidy. These frequencies are consistent with published frequencies of aneuploidy in meiotic metaphase II and first cleavage metaphases of the mouse, providing preliminary validation of sperm hybridization for the detection of aneuploidy. No significant animal or strain differences were observed. In addition, the hyperhaploidy frequencies for murine spermatids were indistinguishable for those for sperm from healthy men obtained by a similar hybridization procedure. These procedures for detecting aneuploid male gametes are examples of ''bridging biomarkers'' between human and animal studies. They have promising applications for investigations of the genetic, reproductive, and toxicological factors leading to abnormal reproductive outcomes of paternal origin, (C) 1995 Wiley-Liss, Inc. C1 UNIV CALIF SAN FRANCISCO,DIV MOLEC CYTOMETRY,SAN FRANCISCO,CA 94143. NATL INST ENVIRONM HLTH SCI,RES TRIANGLE PK,NC. RP WYROBEK, A (reprint author), LAWRENCE LIVERMORE NATL LAB,BIOL & BIOTECHNOL RES PROGRAM L452,LIVERMORE,CA 94550, USA. FU NIEHS NIH HHS [Y01-ES-10203-00] NR 26 TC 25 Z9 25 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 1040-452X J9 MOL REPROD DEV JI Mol. Reprod. Dev. PD FEB PY 1995 VL 40 IS 2 BP 259 EP 266 DI 10.1002/mrd.1080400216 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA QJ182 UT WOS:A1995QJ18200015 PM 7766420 ER PT J AU DROSOS, AA DALAKAS, MC AF DROSOS, AA DALAKAS, MC TI IDENTIFICATION OF MACROPHAGES IN THE MUSCLE BIOPSY PREPARATIONS - A COMPARATIVE-STUDY USING SPECIFIC MONOCLONAL ANTIMACROPHAGE ANTIBODIES AND ACID-PHOSPHATASE REACTION SO MUSCLE & NERVE LA English DT Note DE MYOPATHIES; ENDOMYSIAL MACROPHAGES; ACID PHOSPHATASE REACTION; ANTIMACROPHAGE ANTIBODIES ID INCLUSION-BODY MYOSITIS; INFLAMMATORY MYOPATHIES; POLYMYOSITIS; ANTIGEN C1 NINCDS,MED NEUROL BRANCH,NEUROMUSCULAR DIS SECT,BETHESDA,MD 20892. NR 15 TC 7 Z9 7 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD FEB PY 1995 VL 18 IS 2 BP 242 EP 244 DI 10.1002/mus.880180217 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA QH673 UT WOS:A1995QH67300016 PM 7529891 ER PT J AU SANFORD, KK PARSHAD, R PRICE, FM TARONE, RE LEHMANN, AR AF SANFORD, KK PARSHAD, R PRICE, FM TARONE, RE LEHMANN, AR TI G(2) PHASE REPAIR OF X-RAY-INDUCED CHROMOSOMAL DNA-DAMAGE IN TRICHOTHIODYSTROPHY CELLS SO MUTATION RESEARCH LETTERS LA English DT Article DE TRICHOTHIODYSTROPHY; CHROMATID BREAK; CHROMATID GAP; DNA REPAIR; X-IRRADIATION ID DEFICIENT BRITTLE HAIR; GROUP-D MUTATION; XERODERMA-PIGMENTOSUM; CHROMATID DAMAGE; COMPLEMENTATION GROUPS; ABERRATION PRODUCTION; IONIZING-RADIATION; CANCER; IRRADIATION; PREDISPOSITION AB The repair of X-ray-induced DNA damage during G(2) cell-cycle phase has been examined in lines of skin fibroblasts from three patients with trichothiodystrophy (TTD), one with apparently normal and two with defective nucleotide excision repair (NER). These responses are compared with those of five lines from clinically normal controls, lines from xeroderma pigmentosum (XP), Cockayne syndrome (CS), Down syndrome (DS), and ataxia telangiectasia (AT) patients. Chromosomal DNA repair was measured as the chromatid aberration frequency (CAF) or total number of chromatid breaks and long gaps per 100 metaphase cells, determined 0.5-1.5 h after X-irradiation (53 rad). Chromatid breaks and gaps (as defined herein) represent unrepaired DNA strand breaks. Only one of the TTD lines, TTD 1BR, showed an abnormally high CAF. This line was shown subsequently to be of a different complementation group, representing a new nucleotide excision repair gene. An abnormally high CAF was also observed, as reported previously, in XP-C, AT and DS but not in CS skin fibroblasts. In addition, cell lines were examined for DNA incision activity by an indirect method in which chromatid aberrations were enumerated with or without ara-C, an inhibitor of repair synthesis, added after X-irradiation. All TTD lines had abnormally low incision activity. C1 NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. HOWARD UNIV,COLL MED,DEPT PATHOL,WASHINGTON,DC 20059. UNIV SUSSEX,MRC,CELL MUTAT UNIT,BRIGHTON BN1 9RR,E SUSSEX,ENGLAND. RP SANFORD, KK (reprint author), NCI,CELLULAR & MOLEC BIOL LAB,BLDG 37,BETHESDA,MD 20892, USA. NR 37 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-7992 J9 MUTAT RES LETT JI Mutat. Res. Lett. PD FEB PY 1995 VL 346 IS 2 BP 107 EP 114 DI 10.1016/0165-7992(95)90058-6 PG 8 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA QL238 UT WOS:A1995QL23800007 PM 7885400 ER PT J AU DEAN, M AF DEAN, M TI RESOLVING DNA MUTATIONS SO NATURE GENETICS LA English DT Editorial Material ID SINGLE BASE SUBSTITUTIONS; GENOMIC DNA; MISMATCHES RP DEAN, M (reprint author), NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,HUMAN GENET SECT,FREDERICK,MD 21702, USA. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 14 TC 12 Z9 12 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 1995 VL 9 IS 2 BP 103 EP 104 DI 10.1038/ng0295-103 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA QE672 UT WOS:A1995QE67200004 PM 7719330 ER PT J AU PANTALEO, G FAUCI, AS AF PANTALEO, G FAUCI, AS TI APOPTOSIS IN HIV-INFECTION SO NATURE MEDICINE LA English DT Editorial Material ID T-CELLS; DEATH; LYMPHOCYTES; ACTIVATION; AIDS; HYPOTHESIS AB It is reported that DNA fragmentation (indicating apoptosis) is rarely observed in HIV-1 or SIV-producing infected cells, and HIV-1 or SIV RNA is rarely (0-1%) observed in apoptotic cells. What is the role of apoptosis in the pathogenicity of HIV infection? (pages 129-134). RP PANTALEO, G (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,BETHESDA,MD 20892, USA. RI Pantaleo, Giuseppe/K-6163-2016 NR 16 TC 57 Z9 57 U1 0 U2 5 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 FEB PY 1995 VL 1 IS 2 BP 118 EP 120 DI 10.1038/nm0295-118 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA QX558 UT WOS:A1995QX55800017 PM 7585004 ER PT J AU DIEHL, SR AF DIEHL, SR TI SAND IN THE SHEETS SO NATURE MEDICINE LA English DT Editorial Material ID ALZHEIMERS-DISEASE; GENE AB A demonstration of inhibition of beta-sheets in both reactive amyloid, using an in vivo mouse model, and synthetic Alzheimer (beta) amyloid, in vitro (pages 143-148). RP DIEHL, SR (reprint author), NIDR,DEODP,MOLEC EPIDEMIOL & DIS INDICATORS BRANCH,BETHESDA,MD 20892, USA. NR 17 TC 3 Z9 3 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 FEB PY 1995 VL 1 IS 2 BP 120 EP 122 DI 10.1038/nm0295-120 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA QX558 UT WOS:A1995QX55800019 PM 7585005 ER PT J AU FINKEL, TH TUDORWILLIAMS, G BANDA, NK COTTON, MF CURIEL, T MONKS, C BABA, TW RUPRECHT, RM KUPFER, A AF FINKEL, TH TUDORWILLIAMS, G BANDA, NK COTTON, MF CURIEL, T MONKS, C BABA, TW RUPRECHT, RM KUPFER, A TI APOPTOSIS OCCURS PREDOMINANTLY IN BYSTANDER CELLS AND NOT IN PRODUCTIVELY INFECTED-CELLS OF HIV-INFECTED AND SIV-INFECTED LYMPH-NODES SO NATURE MEDICINE LA English DT Article ID CD4+ T-CELLS; ENVELOPE GLYCOPROTEIN; DEATH; AIDS; MECHANISM; DNA; LYMPHOCYTES; DEPLETION; RNA; PCR AB Although 13 years have passed since identification of human immunodeficiency virus-1 (HIV-1) as the cause of AIDS, we do not yet know how HIV kills its primary target, the T cell that carries the CD4 antigen. We and others have shown an increase in the percentage of apoptotic cells among circulating CD4(+) (and CD8(+)) T cells of HIV-seropositive individuals and an increase in frequency of apoptosis with disease progression. However, it is not known if this apoptosis occurs in infected or uninfected T cells. We show here, using in situ labelling of lymph nodes from HIV-infected children and SIV-infected macaques, that apoptosis occurs predominantly in bystander cells and not in the productively infected cells themselves. These data have implications for pathogenesis and therapy, namely, arguing that rational drug therapy may involve combination agents targeting viral replication in infected cells and apoptosis of uninfected cells. C1 UNIV COLORADO,HLTH SCI CTR,DEPT PEDIAT,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,DEPT IMMUNOL,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,DEPT BIOCHEM BIOPHYS & GENET,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,DEPT INFECT DIS,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,DEPT CELL & STRUCT BIOL,DENVER,CO 80262. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,VIRAL PATHOGENESIS LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. TUFTS UNIV,SCH MED,DIV NEWBORN MED,DEPT PEDIAT,BOSTON,MA 02111. RP FINKEL, TH (reprint author), NATL JEWISH CTR IMMUNOL & RESP MED,DIV BASIC SCI,DEPT PEDIAT,1400 JACKSON ST,DENVER,CO 80206, USA. FU NIAID NIH HHS [P01-AI29903A, R01-AI35513]; PHS HHS [R01-A130575A] NR 34 TC 720 Z9 730 U1 0 U2 10 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 FEB PY 1995 VL 1 IS 2 BP 129 EP 134 DI 10.1038/nm0295-129 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA QX558 UT WOS:A1995QX55800022 PM 7585008 ER PT J AU ERINOFF, L AF ERINOFF, L TI GENERAL-CONSIDERATIONS IN ASSESSING NEUROTOXICITY USING NEUROANATOMICAL METHODS SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article ID RAT; MPTP AB Neurotoxicology is a major focus of scientists and policy makers. Neurotoxicological investigations provide vital information needed by regulatory scientists to protect public health and can also elucidate fundamental mechanisms governing nervous system function and enhance our understanding of neurodegenerative diseases as well. A definition of neurotoxicity, developed by the Interagency Committee on Neurotoxicology, includes both permanent and reversible adverse effects on the nervous system. There are a number of factors that can greatly affect the outcome of any study designed to assess neurotoxicity, such as the choice of animal species, dose and dosage regimen, and route of administration. In considering neuroanatomical methodologies for assessing neurotoxicity, it is important to evaluate each technique for such Factors as: limits of detection (sensitivity and signal to noise ratio), ability to be quantified, sampling problems, what is being measured and what can interfere with this measurement. Other questions relating to the strengths and weaknesses of neuroanatomical techniques that should be addressed include: is the technique difficult to perform? Is it reproducible? Which elements of the nervous system are best evaluated? Does the technique reveal the neuronal circuitry involved in the neurotoxic effect? Is successful application of the technique dependent on timing factors? Clearly, there are many factors that can influence the assessment of neurotoxicity so that it is best to base this assessment on converging data based on complementary techniques. RP ERINOFF, L (reprint author), NIDA,DIV BASIC RES,NEUROSCI RES BRANCH,500 FISHERS LANE,ROOM 10A-19,ROCKVILLE,MD 20857, USA. NR 13 TC 5 Z9 7 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD FEB PY 1995 VL 26 IS 2 BP 111 EP 114 DI 10.1016/0197-0186(94)00105-4 PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA QL609 UT WOS:A1995QL60900002 PM 7599531 ER PT J AU SAVITT, JW TRISLER, D HILT, DC AF SAVITT, JW TRISLER, D HILT, DC TI MOLECULAR-CLONING OF TOPAP - A TOPOGRAPHICALLY GRADED PROTEIN IN THE DEVELOPING CHICK VISUAL-SYSTEM SO NEURON LA English DT Article ID LEUCINE-ZIPPER; COILED COILS; VESICULAR TRANSPORT; NERVOUS-SYSTEM; RETINA; EXPRESSION; POSITION; MOTIF; EPIMORPHIN; SEQUENCES AB Topographically graded molecules representing position-specific differences among otherwise similar cells are thought to play a role in the patterning of the developing nervous system. In the embryonic chick visual system, a 40 kDa protein, TOPAP, is expressed in a posterior > anterior gradient in the retina and in an inverted anterior > posterior gradient in the optic tectum, the major retinal projection area. Here we report the isolation and nucleotide sequencing of a complementary DNA clone encoding the chick TOPAP protein and demonstrate that the mRNA encoding this coiled-coil integral membrane protein is topographically graded within the retina and is present in a variety of chick tissues. C1 UNIV MARYLAND,SCH MED,DEPT BIOL CHEM,BALTIMORE,MD 21201. NHLBI,BIOCHEM GENET LAB,BETHESDA,MD 20892. RP SAVITT, JW (reprint author), UNIV MARYLAND,SCH MED,DEPT NEUROL,BALTIMORE,MD 21201, USA. NR 49 TC 38 Z9 38 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD FEB PY 1995 VL 14 IS 2 BP 253 EP 261 DI 10.1016/0896-6273(95)90283-X PG 9 WC Neurosciences SC Neurosciences & Neurology GA QH294 UT WOS:A1995QH29400005 PM 7857637 ER PT J AU LYFORD, GL YAMAGATA, K KAUFMANN, WE BARNES, CA SANDERS, LK COPELAND, NG GILBERT, DJ JENKINS, NA LANAHAN, AA WORLEY, PF AF LYFORD, GL YAMAGATA, K KAUFMANN, WE BARNES, CA SANDERS, LK COPELAND, NG GILBERT, DJ JENKINS, NA LANAHAN, AA WORLEY, PF TI ARC, A GROWTH-FACTOR AND ACTIVITY-REGULATED GENE, ENCODES A NOVEL CYTOSKELETON-ASSOCIATED PROTEIN THAT IS ENRICHED IN NEURONAL DENDRITES SO NEURON LA English DT Article ID LONG-TERM POTENTIATION; FACTOR MESSENGER-RNAS; IMMEDIATE-EARLY GENES; DENTATE GYRUS; RAT-BRAIN; UNANESTHETIZED RATS; SPECTRIN SUBTYPES; SYNAPTIC ACTIVITY; ALPHA-SPECTRIN; VISUAL-CORTEX AB Neuronal activity is an essential stimulus for induction of plasticity and normal development of the CNS. We have used differential cloning techniques to identify a novel immediate-early gene (IEG) cDNA that is rapidly induced in neurons by activity in models of adult and developmental plasticity. Both the mRNA and the encoded protein are enriched in neuronal dendrites. Analysis of the deduced amino acid sequence indicates a region of homology with alpha-spectrin, and the full-length protein, prepared by in vitro transcription/translation, coprecipitates with F-actin. Confocal microscopy of the native protein in hippocampal neurons demonstrates that the IEG-encoded protein is enriched in the subplasmale!mmal cortex of the cell body and dendrites and thus colocalizes with the actin cytoskeletal matrix. Accordingly, we have termed the gene and encoded prote8n Ale (activity-regulated cytoskeleton-associated protein). Our observations suggest that Are may play a role in activity-dependent plasticity of dendrites. C1 JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROL, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, HOWARD HUGHES MED INST, BALTIMORE, MD 21205 USA. UNIV ARIZONA, DEPT PSYCHOL & NEUROL, TUCSON, AZ 85724 USA. UNIV ARIZONA, DIV NEUROANAL SYST MEMROY & AGING, TUCSON, AZ 85724 USA. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, MAMMALIAN GENET LAB, FREDERICK, MD 21702 USA. RP LYFORD, GL (reprint author), JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROSCI, BALTIMORE, MD 21205 USA. FU NEI NIH HHS [EY09374]; NIA NIH HHS [AG09219]; NIMH NIH HHS [MH18030] NR 72 TC 722 Z9 735 U1 1 U2 39 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD FEB PY 1995 VL 14 IS 2 BP 433 EP 445 DI 10.1016/0896-6273(95)90299-6 PG 13 WC Neurosciences SC Neurosciences & Neurology GA QH294 UT WOS:A1995QH29400021 PM 7857651 ER PT J AU DUNCAN, WC JOHNSON, KA WEHR, TA AF DUNCAN, WC JOHNSON, KA WEHR, TA TI ANTIDEPRESSANT DRUG-INDUCED HYPOTHALAMIC COOLING IN SYRIAN-HAMSTERS SO NEUROPSYCHOPHARMACOLOGY LA English DT Review DE BODY TEMPERATURE; HYPOTHALAMUS; CIRCADIAN RHYTHM; DEPRESSION; SEROTONIN; ANTIDEPRESSANT DRUGS ID MONOAMINE-OXIDASE INHIBITION; CEREBRAL GLUCOSE-UTILIZATION; CHRONIC CLORGYLINE TREATMENT; SEASONAL AFFECTIVE-DISORDER; LONG-TERM TREATMENT; BODY-TEMPERATURE; SLEEP-DEPRIVATION; CORE TEMPERATURE; CIRCADIAN-RHYTHMS; METABOLIC-RATE AB Antidepressant drugs have been reported to alter the circadian pattern of body temperature, but specific effects an the amplitude or on average body temperature are not consistent, and there have been no specific studies to examine chronic drug effects on brain temperature. To address these issues, hypothalamic temperature (T-hy) was monitored telemetrically in hamsters treated with three antidepressant drugs, the monoamine oxidase inhibitor (MAOI), clorgyline; the 5HT reuptake inhibitor, fluoxetine; and the alkali metal, lithium. For comparison, hamsters were also treated with two neuroleptic drugs, chlorpromazine and haloperidol. Each of the three antidepressant drugs, but neither of the neuroleptic drugs, produced a chronic decrease in diurnal (vest-phase) hypothalamic temperature. The T-hy-decreasing effect of clorgyline was not prevented by pinealectomy, and T-hy decreased more than peritoneal temperature (T-p), thus reducing the temperature difference between the hypothalamus and the peritoneal cavity. Less general effects of the antidepressants were also observed. Clorgyline and fluoxetine, but not lithium, delayed the 24-hour rhythm of T-hy. Clorgyline and lithium, but not fluoxetine decreased the average 24-hour T-hy. The neuroleptics chlorpromazine and haloperidol decreased the amplitude of the 24-hour T-hy rhythm. The fact that chronic antidepressant drugs, but not neuroleptic drugs, decrease T-hy is consistent with their different neurotransmitter effects and clinical applications, and raises the possibility that their antidepressant property might be related to their capacity to decrease T-hy during sleep. RP DUNCAN, WC (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,ROOM 4S-239,BLDG 10,BETHESDA,MD 20892, USA. NR 101 TC 20 Z9 20 U1 1 U2 2 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD FEB PY 1995 VL 12 IS 1 BP 17 EP 37 DI 10.1016/0893-133X(94)00055-5 PG 21 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA QK038 UT WOS:A1995QK03800003 PM 7766283 ER PT J AU HURD, YL HERKENHAM, M AF HURD, YL HERKENHAM, M TI THE HUMAN NEOSTRIATUM SHOWS COMPARTMENTALIZATION OF NEUROPEPTIDE GENE-EXPRESSION IN DORSAL AND VENTRAL REGIONS - AN IN-SITU HYBRIDIZATION HISTOCHEMICAL ANALYSIS SO NEUROSCIENCE LA English DT Article ID MESSENGER-RNA EXPRESSION; DELTA-OPIATE RECEPTORS; HUMAN GLOBUS PALLIDUS; ALPHA-NEO-ENDORPHIN; SUBSTANCE-P; INSITU HYBRIDIZATION; BASAL GANGLIA; HUMAN-BRAIN; RAT-BRAIN; MET-ENKEPHALIN AB Expression of neuropeptide messenger RNAs in striatal neurons was studied in post mortem human brain tissue by the use of in situ hybridization histochemistry. Clusters of cells expressing high levels of prodynorphin messenger RNA, and less strikingly, preprotachykinin messenger RNA, were prominent in the caudate nucleus and were present but less pronounced in the putamen. Proenkephalin and prosomatostatin messenger RNA-containing cells were more homogeneously distributed throughout the striatum, though the latter were much sparser. The four neuropeptide messenger RNA patterns in the nucleus accumbens were rather homogeneous compared with the dorsal striatum. Of these, prodynorphin messenger RNA showed a higher level of expression per cell in the nucleus accumbens relative to the dorsal striatum. The relationship of neuropeptide-containing cell clusters to the striosomal organization was characterized by looking at the register of these markers with patterns of low acetylcholinesterase activity and dense mu opiate receptor binding. In the caudate and putamen, clusters of cells expressing high levels of dynorphin and preprotachykinin messenger RNAs were clearly in register with the striosomes. The accumbens was defined by high prodynorphin messenger RNA levels, both low and high levels of acetylcholinesterase staining, and very low to absent mu opiate receptor binding. The distribution of high-expressing prodynorphin messenger RNA-containing cells-to the patch compartment and throughout the entire ventral striatum/nucleus accumbens region-defines the limbic domain of the neostriatum and suggests particular relevance to human striatal organization and function, because the distribution of this opioid neuropeptide is considerably more compartmentalized in human than in non-human species. C1 NIMH,FUNCT NEUROANAT SECT,BETHESDA,MD 20892. OI Herkenham, Miles/0000-0003-2228-4238 NR 86 TC 48 Z9 48 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD FEB PY 1995 VL 64 IS 3 BP 571 EP 586 DI 10.1016/0306-4522(94)00417-4 PG 16 WC Neurosciences SC Neurosciences & Neurology GA QD109 UT WOS:A1995QD10900001 PM 7536307 ER PT J AU WARD, RP HAMBLIN, MW LACHOWICZ, JE HOFFMAN, BJ SIBLEY, DR DORSA, DM AF WARD, RP HAMBLIN, MW LACHOWICZ, JE HOFFMAN, BJ SIBLEY, DR DORSA, DM TI LOCALIZATION OF SEROTONIN SUBTYPE-6 RECEPTOR MESSENGER-RNA IN THE RAT-BRAIN BY IN-SITU HYBRIDIZATION HISTOCHEMISTRY SO NEUROSCIENCE LA English DT Article ID ATYPICAL ANTIPSYCHOTIC-DRUGS; MOLECULAR-CLONING; ADENYLATE-CYCLASE; HIGH-AFFINITY; EXPRESSION; GENE; HIPPOCAMPUS; SYSTEM AB The serotonin receptor subtype 6, which raises intracellular cyclic AMP via stimulatory G-proteins, has recently been cloned and characterized. To determine the distribution of serotonin subtype 6 messenger RNA, in situ hybridization was performed in coronal sections of rat brain. S-35-labeled riboprobe, complementary to the 5' non-coding region of the serotonin subtype 6 messenger RNA, and a P-33-labeled riboprobe complementary to its 3' non-coding region, were used for hybridization. Serotonin subtype 6 receptor message was found in serotonin projection fields, rather than regions of serotonin-containing cell bodies, suggesting that the receptor is mainly postsynaptic. Hybridization signal was highest in olfactory tubercle, as well as prominent in the striatum, nucleus accumbens, dentate gyrus, and CA1, CA2 and CA3 of the hippocampus. Less intense hybridization was observed in cerebellum, some diencephalic nuclei, the amygdala, and layers 2, 3, 4 and 6 of the cortex. This pattern of hybridization was observed with both probes, but not when sense transcripts were used. Because the serotonin subtype 6 receptor has a high affinity for the atypical antipsychotic clozapine, and because striatum and nucleus accumbens are proposed sites of antipsychotic drug effects, the possibility is raised that this receptor may play an important role in mediating the effects of the atypical antipsychotic agents. C1 VET AFFAIRS MED CTR,CTR GERIATR RES EDUC & CLIN,SEATTLE,WA. NINCDS,EXPTL THERAPEUT BRANCH,MOLEC NEUROPHARMACOL SECT,BETHESDA,MD 20892. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RP WARD, RP (reprint author), UNIV WASHINGTON,DEPT PSYCHIAT & BEHAV SCI,DEPT PHARMACOL,SEATTLE,WA 98195, USA. FU NIGMS NIH HHS [GM07266]; NINDS NIH HHS [NS20311] NR 25 TC 176 Z9 179 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD FEB PY 1995 VL 64 IS 4 BP 1105 EP 1111 DI 10.1016/0306-4522(94)00439-C PG 7 WC Neurosciences SC Neurosciences & Neurology GA QH290 UT WOS:A1995QH29000020 PM 7753378 ER PT J AU NEGGERS, Y GOLDENBERG, RL CLIVER, SP HOFFMAN, HJ CUTTER, GR AF NEGGERS, Y GOLDENBERG, RL CLIVER, SP HOFFMAN, HJ CUTTER, GR TI THE RELATIONSHIP BETWEEN MATERNAL AND NEONATAL ANTHROPOMETRIC MEASUREMENTS IN TERM NEWBORNS SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID LOW-BIRTH-WEIGHT; PREPREGNANCY WEIGHT; PREGNANCY; GROWTH; GAIN; FAT; DETERMINANTS; DEPOSITION; SIZE AB Objective: To determine whether measures of maternal lean mass, fat reserves, or a combination of both best predict the various measures of newborn size at birth. Methods: The population consisted of 1205 multiparous, predominantly black women at high risk for fetal growth retardation, who delivered at term at the University of Alabama at Birmingham. Maternal body mass index (BMI) was calculated using the reported pre-pregnancy weight. Maternal anthropometric measurements taken at mid-pregnancy included skinfold thicknesses, lean body mass, and mid-arm, calf, and wrist circumferences. Weight and 11 other neonatal measurements were made within 24 hours of birth and related to various maternal anthropometric measurements. Results: Reported maternal pre-pregnancy weight was the best predictor of all neonatal size measures except for the neonatal skinfold thicknesses, which were better predicted by the pre-pregnancy BMI. For example, the range between the tenth and 90th percentiles of maternal pre-pregnancy weight (46.3-86.4 kg) was associated with 295 g birth weight compared to only 188 g birth weight for a measure of lean body mass. Conclusion: Most maternal anthropometric measurements were significantly associated with most neonatal measurements. However, for nearly every neonatal measurement considered, the maternal pre-pregnancy weight was the best predictor. C1 UNIV ALABAMA,DEPT OBSTET & GYNECOL,CTR OBSTET RES,BIRMINGHAM,AL 35233. UNIV ALABAMA,DEPT HUMAN NUTR,TUSCALOOSA,AL. NICHHD,ROCKVILLE,MD. FU NICHD NIH HHS [N01-HD-4-2811]; PHS HHS [282-92-0055] NR 20 TC 38 Z9 42 U1 0 U2 1 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 1995 VL 85 IS 2 BP 192 EP 196 DI 10.1016/0029-7844(94)00364-J PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA QC632 UT WOS:A1995QC63200006 PM 7824229 ER PT J AU HARTGE, P AF HARTGE, P TI RATES AND RISKS OF OVARIAN-CANCER IN SUBGROUPS OF WHITE WOMEN IN THE UNITED-STATES - REPLY SO OBSTETRICS AND GYNECOLOGY LA English DT Letter RP HARTGE, P (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EPN 443,6130 EXECUT BLVD,ROCKVILLE,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 1995 VL 85 IS 2 BP 320 EP 320 DI 10.1016/S0029-7844(95)80188-X PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA QC632 UT WOS:A1995QC63200036 ER PT J AU CHEEVER, AW FINKELMAN, FD COX, TM AF CHEEVER, AW FINKELMAN, FD COX, TM TI ANTI-INTERLEUKIN-4 TREATMENT DIMINISHES SECRETION OF TH2 CYTOKINES AND INHIBITS HEPATIC-FIBROSIS IN MURINE SCHISTOSOMIASIS-JAPONICA SO PARASITE IMMUNOLOGY LA English DT Article DE SCHISTOSOMA-JAPONICUM; CYTOKINES; ANTI-IL-4; HEPATIC FIBROSIS; GRANULOMATOUS INFLAMMATION ID GRANULOMA-FORMATION; IL-4; MANSONI; MICE; CELLS; INTERLEUKIN-5; ANTIBODIES; INVIVO; GAMMA AB Anti-interleukin-4 (IL-4) treatment of Schistosoma japonicum-infected mice markedly inhibited in vitro secretion of the Th2 cytokines IL-4 and IL-5 from antigen-stimulated spleen cells, but enhanced the secretion of the Th1 cytokine IFN-gamma. IL-2 secretion was unaffected. Hepatic fibrosis was markedly diminished in anti-IL-4-treated-mice at ten weeks of infection while granulomas around S. japonicum eggs in the livers were slightly-to-moderately increased in size. The number of eggs per worm pair in the tissues and feces did not differ significantly in treated and untreated mice. These findings suggest that Th2 cytokine responses are important in the genesis of schistosomal hepatic fibrosis. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT MED,BETHESDA,MD 20814. RP CHEEVER, AW (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. NR 19 TC 27 Z9 32 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0141-9838 J9 PARASITE IMMUNOL JI Parasite Immunol. PD FEB PY 1995 VL 17 IS 2 BP 103 EP 109 DI 10.1111/j.1365-3024.1995.tb00972.x PG 7 WC Immunology; Parasitology SC Immunology; Parasitology GA QJ381 UT WOS:A1995QJ38100007 PM 7761107 ER PT J AU SHAHABUDDIN, M AF SHAHABUDDIN, M TI CHITINASE AS A VACCINE SO PARASITOLOGY TODAY LA English DT Editorial Material ID PARASITE CHITINASE; TRANSMISSION; MALARIA; VECTOR RP SHAHABUDDIN, M (reprint author), NIAID,MALARIA RES LAB,MOLEC VACCINE SECT,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 11 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0169-4758 J9 PARASITOL TODAY JI Parasitol. Today PD FEB PY 1995 VL 11 IS 2 BP 46 EP 47 DI 10.1016/0169-4758(95)80112-X PG 2 WC Parasitology SC Parasitology GA QF007 UT WOS:A1995QF00700002 PM 15275371 ER PT J AU REMADI, S FINCI, V ISMAIL, A ZACHARIE, S VASSILAKOS, P AF REMADI, S FINCI, V ISMAIL, A ZACHARIE, S VASSILAKOS, P TI HERPETIC ENDOMETRITIS AFTER PREGNANCY SO PATHOLOGY RESEARCH AND PRACTICE LA English DT Article DE ENDOMETRIUM HERPES SIMPLEX VIRUS INFECTION ID SIMPLEX VIRUS-INFECTION AB A case of endometrial herpex simplex virus infection with severe uterine post-partum bleeding is reported. Histopathologic analysis of curettage samples revealed endometrial necrosis and diffuse herpes-type nuclear inclusions in the glandular epithelial cells. Immunohistochemistry, in situ hybridisation, and electron microscopy confirmed the diagnosis. C1 HOP CANTONAL UNIV GENEVA,INST PATHOL CLIN,DIV ANAT GYNECOOBSTET,GENEVA,SWITZERLAND. NIAID,BETHESDA,MD 20892. NR 13 TC 15 Z9 16 U1 0 U2 1 PU GUSTAV FISCHER VERLAG PI STUTTGART PA WOLLGRASWEG 49 POSTFACH 72 01 43, D-70577 STUTTGART, GERMANY SN 0344-0338 J9 PATHOL RES PRACT JI Pathol. Res. Pract. PD FEB PY 1995 VL 191 IS 1 BP 31 EP 34 PG 4 WC Pathology SC Pathology GA QM414 UT WOS:A1995QM41400005 PM 7651930 ER PT J AU MCCARDLE, P QUATRANO, LA AF MCCARDLE, P QUATRANO, LA TI WORKSHOP ON PEDIATRIC AIDS REHABILITATION - A SUMMARY SO PEDIATRIC AIDS AND HIV INFECTION-FETUS TO ADOLESCENT LA English DT Editorial Material C1 NICHHD,NCMRR,ARMRB,EXECUT BLDG,RM 2A03,6100 EXECUT BLVD,MSC 7510,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1045-5418 J9 PEDIATR AIDS HIV INF JI Pediatr. AIDS HIV Infect.-Fetus Adolesc. PD FEB PY 1995 VL 6 IS 1 BP 14 EP 17 PG 4 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA QM366 UT WOS:A1995QM36600003 PM 11361736 ER PT J AU VATSIS, KP WEBER, WW BELL, DA DUPRET, JM EVANS, DAP GRANT, DM HEIN, DW LIN, HJ MEYER, UA RELLING, MV SIM, E SUZUKI, T YAMAZOE, Y AF VATSIS, KP WEBER, WW BELL, DA DUPRET, JM EVANS, DAP GRANT, DM HEIN, DW LIN, HJ MEYER, UA RELLING, MV SIM, E SUZUKI, T YAMAZOE, Y TI NOMENCLATURE FOR N-ACETYLTRANSFERASES SO PHARMACOGENETICS LA English DT Review DE ACETYLATION POLYMORPHISMS; NAT NOMENCLATURE; N-ACETYLTRANSFERASES ID HYDROXYARYLAMINE O-ACETYLTRANSFERASE; ARYLHYDROXAMIC ACID N,O-ACYLTRANSFERASE; CHICKEN PINEAL-GLAND; SLOW ACETYLATOR MICE; FULL-LENGTH CDNA; HUMAN-LIVER; NUCLEOTIDE-SEQUENCE; METABOLIC-ACTIVATION; AROMATIC-AMINES; HAMSTER LIVER AB A consolidated classification system is described for prokaryotic and eukaryotic N-acetyltransferases in accordance with the international rules for gene nomenclature, The root symbol (NAT) specifically identifies the genes that code for the N-acetyltransferases, and NAT* loci encoding proteins with similar function are distinguished by Arabic numerals, Allele characters, denoted by Arabic numbers or by a combination of Arabic numbers and uppercase Latin letters, are separated from gene loci by an asterisk, and the entire gene-allele symbols are italicized, Alleles at the different NAT* loci have been numbered chronologically irrespective of the species of origin, For designation of genotypes at a single NAT* locus, a slash serves to separate the alleles; in phenotype designations, which are not italicized, alleles are separated by a comma. C1 NIEHS, BIOCHEM RISK ANAL LAB, RES TRIANGLE PK, NC 27709 USA. HOP ROBERT DEBRE, INSERM, U120, F-75019 PARIS, FRANCE. RIYADH ARMED FORCES HOSP, DEPT MED, RIYADH 11159, SAUDI ARABIA. HOSP SICK CHILDREN, RES INST, DIV CLIN PHARMACOL & TOXICOL, TORONTO, ON M5G 1X8, CANADA. UNIV N DAKOTA, SCH MED, DEPT PHARMACOL & TOXICOL, GRAND FORKS, ND 58202 USA. UNIV CALIF LOS ANGELES, HARBOR MED CTR, DEPT PEDIAT, DIV MED GENET, TORRANCE, CA 90509 USA. UNIV BASEL, BIOCTR, DEPT PHARMACOL, CH-4056 BASEL, SWITZERLAND. ST JUDE CHILDRENS RES HOSP, DEPT PHARMACEUT, MEMPHIS, TN 38101 USA. UNIV OXFORD, DEPT PHARMACOL, OXFORD OX1 3QT, ENGLAND. KYUSHU UNIV, MED INST BIOREGULAT, DEPT CLIN GENET, BEPPU, OITA 874, JAPAN. KEIO UNIV, SCH MED, DEPT PHARMACOL, TOKYO 160, JAPAN. RP VATSIS, KP (reprint author), UNIV MICHIGAN, SCH MED, DEPT PHARMACOL, 1301 MED SCI RES BLDG 3, 1150 W MED CTR DR, ANN ARBOR, MI 48109 USA. RI Hein, David/A-9707-2008 FU NCI NIH HHS [CA34627]; NCRR NIH HHS [MO1 RR 00042]; NIGMS NIH HHS [GM44965] NR 120 TC 359 Z9 364 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD FEB PY 1995 VL 5 IS 1 BP 1 EP 17 DI 10.1097/00008571-199502000-00001 PG 17 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA QL060 UT WOS:A1995QL06000001 PM 7773298 ER PT J AU ROACHE, JD MEISCH, RA HENNINGFIELD, JE JAFFE, JH KLEIN, S SAMPSON, A AF ROACHE, JD MEISCH, RA HENNINGFIELD, JE JAFFE, JH KLEIN, S SAMPSON, A TI REINFORCING EFFECTS OF TRIAZOLAM IN SEDATIVE ABUSERS - CORRELATION OF DRUG LIKING AND SELF-ADMINISTRATION MEASURES SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE TRIAZOLAM; DRUG ABUSE; BENZODIAZEPINES; DRUG SELF-ADMINISTRATION; HUMANS; ABUSE LIABILITY ID RHESUS-MONKEYS; DIAZEPAM; PERFORMANCE; LIABILITY; HUMANS; BENZODIAZEPINES; PREFERENCE; PLACEBO AB Six male subjects with histories of sedative abuse were allowed to orally self-administer a maximum of 18 color-coded triazolam and placebo capsules during daily 3-h sessions. The schedule of reinforcement was a signaled fixed-interval 10-min schedule in which triazolam and placebo were concurrently available as mutually exclusive choices. Triazolam was shown to be a reinforcer in four of the six subjects. The two subjects who did not self-administer triazolam in preference to placebo also had lesser histories of drug dependence. Self-administration of triazolam (0.125 or 0.25 mg per capsule) was generally stable over 7-10 days. Manipulations of triazolam dose (0.0312-0.25 mg) per capsule in two subjects showed that the number of capsules self-administered was inversely related to capsule dose. Subject ratings of drug liking obtained from experimenter-administered doses of triazolam were correlated with self-administration behavior occurring 1-7 days later. Of the subject ratings, next day ratings obtained on the day after dosing resulted in significant correlations whereas same day ratings obtained while subjects were under the influence of triazolam did not. These results have important implications for abuse liability prediction and suggest that next day ratings have greater predictive validity than measures collected while subjects are under the influence of benzodiazepines. C1 NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. NR 25 TC 20 Z9 20 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD FEB PY 1995 VL 50 IS 2 BP 171 EP 179 DI 10.1016/0091-3057(94)00281-M PG 9 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA QE310 UT WOS:A1995QE31000006 PM 7740055 ER PT J AU MAZZOLAPOMIETTO, P AULAKH, CS MURPHY, DL AF MAZZOLAPOMIETTO, P AULAKH, CS MURPHY, DL TI THE NMDA RECEPTOR COMPLEX MODULATES CLONIDINE-INDUCED INCREASES IN GROWTH-HORMONE LEVELS IN RATS SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Note DE 5,7-DICHLOROKYNURENIC ACID; DNQX; DIZOCILPINE; GLYCINE; GROWTH HORMONE RELEASING FACTOR ID N-METHYL-D; GLYCINE BINDING-SITE; FEMALE RATS; SECRETION; ACID; ANTAGONISTS; RESPONSES; RELEASE AB Intraperitoneal administration of clonidine (50 mu g/kg) produced increases in growth hormone levels in male Wistar rats. Pretreatment with NMDA receptor antagonists including (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP/NMDA site), ifenprodril (polyamine site), and dizocilpine maleate (MK-801) or phencyclidine (PCP) (channel blockers) did not have any significant effect on clonidine-induced increases in growth hormone levels. In contrast, pretreatment with 5,7-dichlorokynurenic acid and 6,7-dinitroquinoxaline-2,3-dione (DNQX) (NMDA receptor-associated glycine site antagonists) significantly attenuated clonidine-induced increases in growth hormone levels. Attenuation of clonidine's effect on growth hormone levels by NMDA receptor-associated glycine site antagonists appears most likely due to an interaction between their effects on the NMDA receptor complex with growth hormone releasing factor. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NR 20 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD FEB PY 1995 VL 50 IS 2 BP 305 EP 307 DI 10.1016/0091-3057(94)00279-R PG 3 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA QE310 UT WOS:A1995QE31000025 PM 7740072 ER PT J AU WITT, DM YOUNG, LJ CREWS, D AF WITT, DM YOUNG, LJ CREWS, D TI PROGESTERONE MODULATION OF ANDROGEN-DEPENDENT SEXUAL-BEHAVIOR IN MALE-RATS SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE RU486; COPULATION; CORTICOSTERONE; TESTOSTERONE; PROGESTERONE ID HORMONE-RELEASING HORMONE; MEDROXYPROGESTERONE ACETATE; MEDIOBASAL HYPOTHALAMUS; CNEMIDOPHORUS-INORNATUS; PROCEPTIVE BEHAVIOR; LUTEINIZING-HORMONE; PREOPTIC AREA; FEMALE RAT; RECEPTIVITY; ESTROGEN AB The present study examines the effects of physiological levels of progesterone (P) on copulatory behavior in sexually naive male rats. Two weeks after gonadectomy males were implanted with either empty Silastic capsules (BL) or Silastic capsules containing testosterone (T), P, or both (P + T). When tested with an estrous female, all of the gonadally intact males (intact) and none of the BL controls exhibited mounting/intromission behaviors. Mounting was observed in 75% of the T-alone males. More than half (64%) of the P-alone males and 100% P + T males exhibited mounting. In most cases, mounting was followed by intromission responses. Subsequently, intact and gonadectomized males received daily injections of the P antagonist RU486 along with hormone treatment. After receiving RU486, only 63% of the intact males and 71% of the T-alone males mounted successfully. The facilitatory effects of P on copulatory behavior were completely abolished by RU486 treatment. The present studies provide the first evidence in mammals suggesting that P-dependent mechanisms influence neurochemical pathways involved in copulation. C1 NIMH,NEUROPHYSIOL LAB,POOLESVILLE,MD 20837. UNIV TEXAS,INST REPROD BIOL,AUSTIN,TX 78712. UNIV TEXAS,DEPT ZOOL,AUSTIN,TX 78712. FU PHS HHS [R37 41770] NR 39 TC 57 Z9 58 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD FEB PY 1995 VL 57 IS 2 BP 307 EP 313 DI 10.1016/0031-9384(94)00247-3 PG 7 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA QC523 UT WOS:A1995QC52300016 PM 7716208 ER PT J AU GUSTCHINA, A ZDANOV, A SCHALKHIHI, C WLODAWER, A AF GUSTCHINA, A ZDANOV, A SCHALKHIHI, C WLODAWER, A TI A MODEL OF THE COMPLEX BETWEEN INTERLEUKIN-4 AND ITS RECEPTORS SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE CYTOKINES; RECEPTORS; INTERLEUKINS; HOMOLOGY MODELING; STRUCTURE PREDICTION ID COLONY-STIMULATING FACTOR; HUMAN GROWTH-HORMONE; CRYSTAL-STRUCTURE; 3-DIMENSIONAL STRUCTURE; GAMMA-CHAIN; HYPERVARIABLE REGIONS; INTERFERON-GAMMA; LIGAND-BINDING; IL-2 RECEPTOR; HUMAN CD4 AB A three-dimensional model of interleukin-4 (IL-4) bound to one molecule each of the high- and low-affinity receptors (IL-4R and IL-SR gamma) was built, using the crystal structure of the complex of human growth hormone (HGH) with its receptor (HGHR) as a starting model. The modeling of IL-4 with its receptors was based on the conservation of the sequences and on the predicted structural organization for cytokine receptors, and assuming that the binding mode of the ligands would be similar. Analysis of the interface between IL-4 and both receptor molecules was carried out to reveal which residues are important for complex formation. The modeling procedures showed that there were no major problems in maintaining a reasonable fit of IL-4 with the two receptor molecules, in a manner analogous to the complex of HGH-HGHR. Many of the residues that appear by modeling to be important for binding between IL-4 and the receptors have been previously implicated in that role by different methods. A striking motif of aromatic and positively charged residues on the surface of the e-terminal domains of the receptors is highly conserved in the structure of HGH-HGHR and in the models of IL-4 complexed with its receptors. (C) 1995 Wiley-Liss, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,MACROMOLEC STRUCT LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 53 TC 25 Z9 25 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-3585 J9 PROTEINS JI Proteins PD FEB PY 1995 VL 21 IS 2 BP 140 EP 148 DI 10.1002/prot.340210208 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QJ996 UT WOS:A1995QJ99600007 PM 7777489 ER PT J AU MUNTANER, C WOLYNIEC, P MCGRATH, J PULVER, AE AF MUNTANER, C WOLYNIEC, P MCGRATH, J PULVER, AE TI DIFFERENCES IN SOCIAL-CLASS AMONG PSYCHOTIC-PATIENTS AT INPATIENT ADMISSION SO PSYCHIATRIC SERVICES LA English DT Note ID HEALTH AB A cross-sectional assessment of differences in social class and other sociodemographic variables at hospital admission for patients with psychotic disorders was carried out through a systematic survey of psychotic patients admitted to greater Baltimore psychiatric facilities between 1983 and 1989. Female patients, first-admission patients, and patients with bipolar disorder or other, nonschizophrenic psychosis were more likely to have been admitted to community, university, and private hospitals than to state hospitals. Patients in medium and higher social class categories were 1.29 to 2.57 times more likely to be admitted to community, university, and private hospitals than to state hospitals. C1 NIMH,SOCIOENVIRONM STUDIES LAB,BETHESDA,MD 20892. RP MUNTANER, C (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,EPIDEMIOL GENET PROGRAM,BALTIMORE,MD 21205, USA. RI Muntaner, C/A-5043-2010 FU NIMH NIH HHS [MH35712] NR 9 TC 7 Z9 7 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD FEB PY 1995 VL 46 IS 2 BP 176 EP 178 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA QP099 UT WOS:A1995QP09900017 PM 7712257 ER PT J AU HASEMAN, JK AF HASEMAN, JK TI DATA-ANALYSIS - STATISTICAL-ANALYSIS AND USE OF HISTORICAL CONTROL DATA SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT Spring Meeting of the Great-Lakes-Discussion-Group of the Society-of-Toxicologic-Pathologists - Design and Interpretation of Animal Carcinogenicity Studies CY MAR 24, 1994 CL CINCINNATI, OH SP SOC TOXICOL PATHOLOGISTS, GREAT LAKES DISCUSS GRP ID BODY-WEIGHT; ANIMAL CARCINOGENICITY; TUMOR-INCIDENCE; B6C3F1 MICE; REGRESSION-ANALYSIS; CONTROL INFORMATION; F344/N RATS; LONG-TERM; TESTS; SURVIVAL AB Survival-adjusted methods for the statistical analysis of tumor data from long-term rodent carcinogenicity studies are described. Although most of these methods require knowledge of whether individual tumors are ''fatal'' or ''incidental,'' such determinations may be difficult. Several methods for dealing with this and with other data analysis issues are discussed. Historical control tumor data may be useful in the interpretation of rodent carcinogenicity studies, particularly for rare tumors and for borderline effects. Although statistical methods are available for using historical control data in a formal testing framework, the primary difficulty is establishing a database that is truly comparable to the study under evaluation with respect to those factors known to influence tumor occurrence. Major sources of variability in tumor incidence include the animal room environment, dietary factors/body weight, gross necropsy and slide preparation procedures, and histopathology diagnosis. The National Toxicology Program's use of historical control data is briefly described and illustrated. (C) 1995 Academic Press, Inc. RP HASEMAN, JK (reprint author), NIEHS,STAT & BIOMATH BRANCH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 58 TC 33 Z9 34 U1 0 U2 6 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD FEB PY 1995 VL 21 IS 1 BP 52 EP 59 DI 10.1006/rtph.1995.1009 PG 8 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA QK985 UT WOS:A1995QK98500006 PM 7784636 ER PT J AU GIBSON, J MCCONNELL LEBOEUF, B BERTRAM, T HUGHES, D GIBSON, B TURTURRO, A MUNRO HASEMAN SQUIRE LONG, G COHEN WEINGAND, K LOCHNER, D SWENBERG FLAMM AF GIBSON, J MCCONNELL LEBOEUF, B BERTRAM, T HUGHES, D GIBSON, B TURTURRO, A MUNRO HASEMAN SQUIRE LONG, G COHEN WEINGAND, K LOCHNER, D SWENBERG FLAMM TI UNTITLED - DISCUSSION SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Discussion C1 PROCTER & GAMBLE CO,CINCINNATI,OH 45239. NIEHS,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709. ELI LILLY & CO,INDIANAPOLIS,IN 46285. CANTOX,MISSISSAUGA,ON L5N 2X7,CANADA. FLAMM ASSOCIATES,RESTON,VA 22091. NR 0 TC 2 Z9 2 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD FEB PY 1995 VL 21 IS 1 BP 81 EP 86 DI 10.1006/rtph.1995.1013 PG 6 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA QK985 UT WOS:A1995QK98500010 ER PT J AU CASH, JM WILDER, RL AF CASH, JM WILDER, RL TI REFRACTORY RHEUMATOID-ARTHRITIS - THERAPEUTIC OPTIONS SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID METHYLPREDNISOLONE PULSE THERAPY; MONONUCLEAR CELL-PROLIFERATION; DOSE INTRAVENOUS METHOTREXATE; PLACEBO CONTROLLED TRIAL; DISEASE-MODIFYING DRUGS; SEPTIC ARTHRITIS; DOUBLE-BLIND; COMBINATION THERAPY; AGGRESSIVE THERAPY; NITROGEN-MUSTARD AB Because rheumatoid arthritis rarely remits, refractory disease is common. Attention should be paid to aggravating comorbid conditions. Pharmacologic options currently available include cyclosporin, high-dose methotrexate, combination second-line agents, and creative use of corticosteroids. The available literature is reviewed in this article and the potential risks and benefits of the various options are discussed. C1 NIAMSD,INFLAMMATORY JOINT DIS SECT,BETHESDA,MD. RP CASH, JM (reprint author), CLEVELAND CLIN FDN,DEPT RHEUMAT & IMMUNOL DIS,9500 EUCLID AVE,CLEVELAND,OH 44195, USA. NR 118 TC 19 Z9 20 U1 3 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD FEB PY 1995 VL 21 IS 1 BP 1 EP 18 PG 18 WC Rheumatology SC Rheumatology GA QG370 UT WOS:A1995QG37000002 PM 7732162 ER PT J AU GERBER, LH HICKS, JE AF GERBER, LH HICKS, JE TI SURGICAL AND REHABILITATION OPTIONS IN THE TREATMENT OF THE RHEUMATOID-ARTHRITIS PATIENT RESISTANT TO PHARMACOLOGICAL AGENTS SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID NERVE-STIMULATION TNS; OSTEO-ARTHRITIS; MUSCLE STRENGTH; EXERCISE; PAIN; THERAPY; KNEE; EXPERIENCE; DEPRESSION; ENDURANCE AB People with rheumatoid arthritis whose disease is poorly controlled with pharmacologic agents require treatment designed to reduce pain and inflammation and promote function and mechanical alignment. The proper evaluation of the musculoskeletal system and the patient's functional level must be performed. Heat, cold, splints, adaptive equipment, exercise, alternative therapies, and surgery are important adjunctive treatments for disease modulation and to maintain function and well being. RP GERBER, LH (reprint author), NIH,CTR CLIN,DEPT REHABIL MED,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 69 TC 3 Z9 3 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 FEB PY 1995 VL 21 IS 1 BP 19 EP 39 PG 21 WC Rheumatology SC Rheumatology GA QG370 UT WOS:A1995QG37000003 PM 7732168 ER PT J AU FESSLER, BJ BOUMPAS, DT AF FESSLER, BJ BOUMPAS, DT TI SEVERE MAJOR ORGAN INVOLVEMENT IN SYSTEMIC LUPUS-ERYTHEMATOSUS - DIAGNOSIS AND MANAGEMENT SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID METHYLPREDNISOLONE PULSE THERAPY; IMMUNE THROMBOCYTOPENIC PURPURA; TOTAL LYMPHOID IRRADIATION; CORONARY-ARTERY DISEASE; PULMONARY HEMORRHAGE; INTRAVENOUS CYCLOPHOSPHAMIDE; NEUROPSYCHIATRIC LUPUS; AUTOIMMUNE THROMBOCYTOPENIA; MYOCARDIAL-INFARCTION; PERICARDIAL TAMPONADE AB Deterioration in the function of major organs in patients with systemic lupus erythematosus may be due to causes directly related to the disease itself or to non-lupus related causes. In patients with rapidly progressive immune-mediated disease, therapy may be initiated with pulse glucocorticoids alone or in combination with pulse cyclophosphamide. For selected patients with aggressive life-threatening disease or patients refractory to treatment, experimental therapies such as plasmapheresis or intravenous immunoglobulin may be used as adjuncts in their management. C1 NIDDKD,KIDNEY DIS SECT,BLDG 10,ROOM 3N112,9000 ROCKVILLE PIKE RD,BETHESDA,MD 20892. NR 94 TC 28 Z9 29 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 FEB PY 1995 VL 21 IS 1 BP 81 EP 98 PG 18 WC Rheumatology SC Rheumatology GA QG370 UT WOS:A1995QG37000007 PM 7732176 ER PT J AU ADAMS, EM PLOTZ, PH AF ADAMS, EM PLOTZ, PH TI THE TREATMENT OF MYOSITIS - HOW TO APPROACH RESISTANT DISEASE SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID INCLUSION-BODY MYOSITIS; IDIOPATHIC INFLAMMATORY MYOPATHY; HUMAN-IMMUNODEFICIENCY-VIRUS; INTRAVENOUS GAMMA-GLOBULIN; INTERSTITIAL LUNG-DISEASE; ONSET POLYMYOSITIS-DERMATOMYOSITIS; CRICOPHARYNGEUS MUSCLE INVOLVEMENT; DRUG-INDUCED MYOPATHIES; JUVENILE DERMATOMYOSITIS; ADULT DERMATOMYOSITIS AB Idiopathic inflammatory myopathies, polymyositis, dermatomyositis, and inclusion body myositis, are increasingly recognized to cause long-term disability in certain subsets of patients. Because these diseases are infrequent, only retrospective analysis of most treatments are available. In this article, identification of subsets of patients with different prognoses and discussion of confounding factors for increasing weakness are emphasized. The advantages and disadvantages of different therapies for myositis and for extraskeletal muscle features are also discussed. RP ADAMS, EM (reprint author), NIAMSD,ARTHRITIS & RHEUMATISM BRANCH,B10 9N244,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 208 TC 25 Z9 29 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 FEB PY 1995 VL 21 IS 1 BP 179 EP 202 PG 24 WC Rheumatology SC Rheumatology GA QG370 UT WOS:A1995QG37000013 PM 7732167 ER PT J AU CASH, JM WILDER, RL AF CASH, JM WILDER, RL TI TREATMENT-RESISTANT RHEUMATIC DISEASE - PREFACE SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 NIAMSD,BETHESDA,MD 20892. RP CASH, JM (reprint author), CLEVELAND CLIN FDN,DEPT RHEUMAT & IMMUNOL DIS,9500 EUCLID AVE,CLEVELAND,OH 44195, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD FEB PY 1995 VL 21 IS 1 BP R13 EP R13 PG 1 WC Rheumatology SC Rheumatology GA QG370 UT WOS:A1995QG37000001 ER PT J AU BREIER, A AF BREIER, A TI SEROTONIN, SCHIZOPHRENIA AND ANTIPSYCHOTIC DRUG-ACTION SO SCHIZOPHRENIA RESEARCH LA English DT Review DE SEROTONIN; ANTIPSYCHOTIC DRUG; SEROTONIN RECEPTOR; UPTAKE BLOCKADE; (SCHIZOPHRENIA) ID FLUID 5-HYDROXYINDOLEACETIC ACID; DORSOLATERAL PREFRONTAL CORTEX; OBSESSIVE-COMPULSIVE DISORDER; CEREBROSPINAL-FLUID; MOLECULAR-CLONING; HUMAN-BRAIN; MONOAMINE METABOLITES; RAT-BRAIN; NEUROTRANSMITTER RECEPTORS; DOPAMINE NEURONS AB A rapidly growing body of data suggests that dysfunction in serotonergic (5-HT) function may be involved in the pathophysiology of schizophrenia, and that pharmacologic agents for this illness have their therapeutic effects mediated through serotonergic mechanisms. The purpose of this paper is to critically review data relevant to 5-HT's role in the pathophysiology and drug treatment of schizophrenia. Pathophysiologic evidence includes the psychotomimetic effects of lysergic acid (LSD), postmortem studies, single-dose 'challenge' studies and investigations of CSF and peripheral levels of 5-HT and its metabolites. The current nomenclature, potential therapeutic effects and importance of 5-HT receptor subtype antagonism will be examined. In addition, relatively novel strategies of 5-HT uptake blockade and direct acting 5-HT agonists will be assessed. A hypothesis of cortical-subcortical imbalance with an increase in subcortical 5-HT function responsible for positive symptoms and a decrease in prefrontal 5-HT function responsible for negative symptoms is proposed. Future implications of these data are discussed. RP BREIER, A (reprint author), NIMH,EXPTL THERAPEUT BRANCH,9000 ROCKVILLE PIKE,BLDG 10,ROOM 4N212,BETHESDA,MD 20892, USA. NR 167 TC 146 Z9 151 U1 5 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD FEB PY 1995 VL 14 IS 3 BP 187 EP 202 DI 10.1016/0920-9964(94)00043-8 PG 16 WC Psychiatry SC Psychiatry GA QJ227 UT WOS:A1995QJ22700001 PM 7539288 ER PT J AU BUKH, J MILLER, RH PURCELL, RH AF BUKH, J MILLER, RH PURCELL, RH TI GENETIC-HETEROGENEITY OF HEPATITIS-C VIRUS - QUASI-SPECIES AND GENOTYPES SO SEMINARS IN LIVER DISEASE LA English DT Review ID NON-B-HEPATITIS; POLYMERASE CHAIN-REACTION; 5' UNTRANSLATED REGION; NON-A; NUCLEOTIDE-SEQUENCE; E2/NS1 PROTEIN; LIVER-DISEASE; HYPERVARIABLE REGIONS; DIFFERENT COUNTRIES; INTERFERON THERAPY C1 NIAID,DIV AIDS,BETHESDA,MD 20892. RP BUKH, J (reprint author), NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BLDG 7,ROOM 201,7 CTR DR MSC 0740,BETHESDA,MD 20892, USA. RI Yang, Chen/G-1379-2010 NR 195 TC 634 Z9 651 U1 3 U2 23 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0272-8087 J9 SEMIN LIVER DIS JI Semin. Liver Dis. PD FEB PY 1995 VL 15 IS 1 BP 41 EP 63 DI 10.1055/s-2007-1007262 PG 23 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QU745 UT WOS:A1995QU74500005 PM 7597443 ER PT J AU FRIED, MW HOOFNAGLE, JH AF FRIED, MW HOOFNAGLE, JH TI THERAPY OF HEPATITIS-C SO SEMINARS IN LIVER DISEASE LA English DT Review ID NON-B HEPATITIS; RECOMBINANT ALPHA-INTERFERON; CHRONIC NON-A; AUTOIMMUNE CHRONIC HEPATITIS; HUMAN-IMMUNODEFICIENCY-VIRUS; RANDOMIZED CONTROLLED TRIAL; CHRONIC VIRAL-HEPATITIS; TERM FOLLOW-UP; ALFA THERAPY; POSTTRANSFUSION HEPATITIS C1 NIDDKD,BETHESDA,MD 20892. EMORY UNIV,SCH MED,DIV DIGEST DIS,ATLANTA,GA. NR 85 TC 162 Z9 165 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0272-8087 J9 SEMIN LIVER DIS JI Semin. Liver Dis. PD FEB PY 1995 VL 15 IS 1 BP 82 EP 91 DI 10.1055/s-2007-1007265 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QU745 UT WOS:A1995QU74500008 PM 7597447 ER PT J AU ALTER, HJ BRADLEY, DW AF ALTER, HJ BRADLEY, DW TI NON-A, NON-B-HEPATITIS UNRELATED TO THE HEPATITIS-C VIRUS (NON-ABC) SO SEMINARS IN LIVER DISEASE LA English DT Review ID FULMINANT NON-A; VIRAL-HEPATITIS; POSTTRANSFUSION HEPATITIS; APLASTIC-ANEMIA; LIVER-DISEASE; INFECTION; CHIMPANZEES; ANTIBODIES; PARTICLES; IMMUNITY C1 CTR DIS CONTROL,HEPATITIS BRANCH,ATLANTA,GA 30333. RP ALTER, HJ (reprint author), NIH,CTR CLIN,DEPT TRANSFUS MED,BETHESDA,MD 20892, USA. NR 55 TC 105 Z9 111 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0272-8087 J9 SEMIN LIVER DIS JI Semin. Liver Dis. PD FEB PY 1995 VL 15 IS 1 BP 110 EP 120 DI 10.1055/s-2007-1007268 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QU745 UT WOS:A1995QU74500011 PM 7597441 ER PT J AU GNARRA, JR LERMAN, MI ZBAR, B LINEHAN, WM AF GNARRA, JR LERMAN, MI ZBAR, B LINEHAN, WM TI GENETICS OF RENAL-CELL CARCINOMA AND EVIDENCE FOR A CRITICAL ROLE FOR VON HIPPEL-LINDAU IN RENAL TUMORIGENESIS SO SEMINARS IN ONCOLOGY LA English DT Article ID HUMAN CHROMOSOME-3; LUNG-CANCER; SHORT ARM; DISEASE; HETEROZYGOSITY; TRANSLOCATION; TUMORS; REGION; CYTOGENETICS; LOCALIZATION C1 NCI,SURG BRANCH,UROL ONCOL SECT,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 21701. NR 38 TC 67 Z9 68 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD FEB PY 1995 VL 22 IS 1 BP 3 EP 8 PG 6 WC Oncology SC Oncology GA QH176 UT WOS:A1995QH17600002 PM 7855617 ER PT J AU WILTROUT, RH GREGORIO, TA FENTON, RG LONGO, DL GHOSH, P MURPHY, WJ KOMSCHLIES, KL AF WILTROUT, RH GREGORIO, TA FENTON, RG LONGO, DL GHOSH, P MURPHY, WJ KOMSCHLIES, KL TI CELLULAR AND MOLECULAR STUDIES IN THE TREATMENT OF MURINE RENAL-CANCER SO SEMINARS IN ONCOLOGY LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; CYTOKINE GENE-EXPRESSION; ACTIVATED KILLER-CELLS; FLAVONE ACETIC-ACID; REDUCED TUMORIGENICITY; ADOPTIVE IMMUNOTHERAPY; METASTATIC BEHAVIOR; INTERFERON-GAMMA; NECROSIS-FACTOR; INTERLEUKIN-2 C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RP WILTROUT, RH (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,BLDG 560,FREDERICK,MD 21702, USA. NR 61 TC 13 Z9 13 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD FEB PY 1995 VL 22 IS 1 BP 9 EP 16 PG 8 WC Oncology SC Oncology GA QH176 UT WOS:A1995QH17600003 PM 7855624 ER PT J AU PARKINSON, DR SZNOL, M AF PARKINSON, DR SZNOL, M TI HIGH-DOSE INTERLEUKIN-2 IN THE THERAPY OF METASTATIC RENAL-CELL CARCINOMA SO SEMINARS IN ONCOLOGY LA English DT Article ID ACTIVATED KILLER-CELLS; PHASE-II TRIAL; RECOMBINANT INTERLEUKIN-2; CANCER; IMMUNOTHERAPY; TOXICITY; INFUSION RP PARKINSON, DR (reprint author), NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,INVEST DRUG BRANCH,BETHESDA,MD 20892, USA. NR 23 TC 16 Z9 16 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD FEB PY 1995 VL 22 IS 1 BP 61 EP 66 PG 6 WC Oncology SC Oncology GA QH176 UT WOS:A1995QH17600008 PM 7855620 ER PT J AU GOTTESMAN, ME WEISBERG, RA AF GOTTESMAN, ME WEISBERG, RA TI TERMINATION AND ANTITERMINATION OF TRANSCRIPTION IN TEMPERATE BACTERIOPHAGES SO SEMINARS IN VIROLOGY LA English DT Article DE PHAGE LAMBDA; PHAGE HK022; TRANSCRIPTION ANTITERMINATION; TRANSCRIPTION TERMINATION ID ESCHERICHIA-COLI; PHAGE-LAMBDA; N-ANTITERMINATION; RNA-POLYMERASE; GENE PROTEIN; NUN PROTEIN; MUTATIONS; REGION; RECOGNITION; SEQUENCE AB The expression of many genes is controlled at the level of transcript elongation. One of the best understood examples is found in bacteriophage lambda, where interaction of the viral N protein and nut sites with host nus proteins and RNA polymerase suppresses termination of early phage transcription. Bacteriophage HK022, although closely related to lambda, regulates elongation in a surprisingly different way. HK022 expresses a function, Nun, that is related to the it lambda antitermination protein. However Nun has no effect on HK022 transcription, but, instead, specifically provokes termination of it transcripts. The HK022 chromosome contains transcription termination signals that separate functional genes from their cognate promoters. As in lambda, these terminators are suppressed but no HK022 gene is required for antitermination. Both the termination activity of Nun and the suppression of HK022 terminators can be demonstrated in purified in-vitro systems. C1 NICHHD,BETHESDA,MD 20892. RP GOTTESMAN, ME (reprint author), COLUMBIA UNIV,INST CANC RES,701 W 168TH ST,NEW YORK,NY 10032, USA. NR 33 TC 14 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1044-5773 J9 SEMIN VIROL JI Semin. Virol. PD FEB PY 1995 VL 6 IS 1 BP 35 EP 42 DI 10.1016/S1044-5773(05)80007-1 PG 8 WC Virology SC Virology GA QR947 UT WOS:A1995QR94700005 ER PT J AU SKOWYRA, D MCKENNEY, K WICKNER, SH AF SKOWYRA, D MCKENNEY, K WICKNER, SH TI FUNCTION OF MOLECULAR CHAPERONES IN BACTERIOPHAGE AND PLASMID DNA-REPLICATION SO SEMINARS IN VIROLOGY LA English DT Article DE DNAK; DNAJ; GRPE; PHAGE LAMBDA; PLASMID P1 ID HEAT-SHOCK PROTEINS; ESCHERICHIA-COLI DNAJ; SPECIALIZED NUCLEOPROTEIN STRUCTURES; DEPENDENT CLP PROTEASE; LAMBDA-P-PROTEIN; INITIATOR PROTEIN; REPA MONOMERIZATION; ATP HYDROLYSIS; PHAGE-LAMBDA; GRPE AB The heat shock protein 70 molecular chaperone system of DnaK, DnaJ and GrpE is necessary for the replication of several E. coli phage and plasmids. For plasmid P1 DNA replication, this system activates DNA binding by the initiator protein, RepA. Activation exposes the DNA binding domain of RepA through the conversion of RepA dimers to monomers. In apparent contrast, the chaperones act after the assembly of the preprimosomal complex for phage lambda DNA replication. They remodel and rearrange the proteins within the complex to activate the DnaB helicase. The mechanism of action of DnaK, DnaJ and GrpE is, however very likely similar in both of these systems. Members of a new chaperone family, ClpA and ClpX, activate the DNA replication initiator proteins of plasmid P1 and phage lambda, respectively. They also function in the ATP-dependent degradation of these proteins in conjunction with ClpP peptidase. C1 NATL INST STAND & TECHNOL, GAITHERSBURG, MD 20899 USA. RP SKOWYRA, D (reprint author), NCI, MOLEC BIOL LAB, BLDG 37, BETHESDA, MD 20892 USA. NR 83 TC 1 Z9 1 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-5773 J9 SEMIN VIROL JI Semin. Virol. PD FEB PY 1995 VL 6 IS 1 BP 43 EP 51 DI 10.1016/S1044-5773(05)80008-3 PG 9 WC Virology SC Virology GA QR947 UT WOS:A1995QR94700006 ER PT J AU PINSKY, PF AF PINSKY, PF TI SYNCHRONY AND CLUSTERING IN AN EXCITATORY NEURAL-NETWORK MODEL WITH INTRINSIC RELAXATION KINETICS SO SIAM JOURNAL ON APPLIED MATHEMATICS LA English DT Article DE SYNCHRONY; NEURAL NETWORKS; ASYMPTOTICS ID COUPLED OSCILLATORS; PULSE INTERACTIONS AB Synchronized Bring of a population of neurons in the hippocampus has been studied as a model for epilepsy. This paper Formulates an abstract model of an excitatory neural network which is qualitatively derived from a biophysical model of hippocampal neurons. In this model the phase space of an isolated neuron is a cylinder (theta,z); an additional variable s conveys the effects of excitatory coupling between cells. A small parameter epsilon is introduced which represents the ratio of two time scales intrinsic to each neuron. It is proved that under certain conditions this model will possess stable approximately synchronous solutions; these are periodic or quasi-periodic solutions in which all cells fire approximately simultaneously (i.e., within a time interval of duration O(epsilon) relative to the intrinsic cell period). These approximately synchronous solutions persist in the face of cell heterogeneity of magnitude O(1). In the case where the network is homogenous, stable approximately synchronous solutions may exist even when the homogeneous solution is technically unstable. Various cluster states in which cells within a cluster fire approximately synchronously are also discussed. C1 UNIV MARYLAND,DEPT MATH,COLLEGE PK,MD 20742. RP PINSKY, PF (reprint author), NIDDK,MATH RES BRANCH,3RD FLOOR,SUITE 350,BSA BLDG,BETHESDA,MD 20892, USA. NR 22 TC 7 Z9 7 U1 0 U2 3 PU SIAM PUBLICATIONS PI PHILADELPHIA PA 3600 UNIV CITY SCIENCE CENTER PH#382-9800, PHILADELPHIA, PA 19104-2688 SN 0036-1399 J9 SIAM J APPL MATH JI SIAM J. Appl. Math. PD FEB PY 1995 VL 55 IS 1 BP 220 EP 241 DI 10.1137/S0036139993257375 PG 22 WC Mathematics, Applied SC Mathematics GA QG326 UT WOS:A1995QG32600011 ER PT J AU WICHMAN, A AF WICHMAN, A TI ETHICS AND RESEARCH ON HUMAN-SUBJECTS - INTERNATIONAL GUIDELINES - PROCEEDINGS OF THE 26TH CIOMS CONFERENCE - BANKOWSKI,Z, LEVINE,R SO SOCIAL SCIENCE & MEDICINE LA English DT Book Review RP WICHMAN, A (reprint author), NIH,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD FEB PY 1995 VL 40 IS 4 BP 573 EP 573 DI 10.1016/0277-9536(95)90027-6 PG 1 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA QE517 UT WOS:A1995QE51700018 ER PT J AU XU, H GOODMAN, CB PARTILLA, JS NI, Q KAYAKIRI, H RICE, KC ROTHMAN, RB AF XU, H GOODMAN, CB PARTILLA, JS NI, Q KAYAKIRI, H RICE, KC ROTHMAN, RB TI 6-BETA-[(125)IODO]-3,14-DIHYDROXY-17-METHYL-4,5-ALPHA-EPOXYMORPHINAN ([I-125]IOXY-AGO) - A POTENT AND SELECTIVE RADIOLIGAND FOR OPIOID MU-RECEPTORS SO SYNAPSE LA English DT Article DE [I-125] IOXY-AGO; OPIOID MU RECEPTORS; RADIOLIGANDS ID BINDING-SITES; OPIATE RECEPTOR; HIGH-AFFINITY; RAT-BRAIN; AGONIST; (+)-CIS-3-METHYLFENTANYL; EXPRESSION; FOREBRAIN; PEPTIDES; CLONING AB The recent cloning and expression of an opioid mu receptor has opened up new opportunities for research in opioid pharmacology. The relatively low level of transient receptor expression in COS cells emphasizes the need for radioligands with high specific activity and low nonspecific binding with which to label receptors. In addition, recent data indicating that agonists and antagonists bind to different domains on the same receptor protein indicate the utility of having both agonist and antagonist radioligands available for the study of opioid receptor mechanisms. Previous studies characterized the binding of the opioid antagonist 6 beta-[(125)iodo]-3,14-dihydroxy-17-cyclopropyl-methyl-4,5 alpha-epoxymorphinan ([I-125]IOXY) and showed that this naltrexone analog labels mu and kappa(2) receptors in rat and guinea pig brain with high affinity and low nonspecific binding. In the present study, we synthesized the agonist congener of IOXY, 6 beta-iodo-3,14-dihydroxy-17-methyl-4,5 alpha-epoxymorphinan. We named this novel agent IOXY-AGO for IOXY-agonist. Competition binding studies showed that IOXY-AGO has high affinity for mu receptors (Ki = 0.28 nM) and lower affinity for delta (Ki = 18.7 nM) and kappa(1) (Ki = 33.9 nM), kappa(2a) (Ki = 38.4 nM) and kappa(2b) (Ki = 58.2 nM) binding sites. IOXY-AGO was radioiodinated to a specific activity of 2,200 Ci/mmol. [I-125]IOXY-AGO binding was rapid, readily reversible, and characterized by low nonspecific binding. Equilibrium binding studies showed that it labeled a single class of binding sites (Kd = 1.46 nM, B-max = 112 fmol/mg protein) with the characteristics of an opioid mu, receptor. Receptor autoradiography experiments showed that [I-125]IOXY-AGO labeled binding sites with the anatomical distribution of mu receptors. Viewed collectively, these studies suggest that [I-125]IOXY-AGO will be a useful radioligand for characterizing opioid mu,receptors. (C) 1995 Wiley-Liss, Inc.* C1 NIDA,IRP,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD 21224. NIDDK,MED CHEM LAB,BETHESDA,MD 20892. NR 20 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD FEB PY 1995 VL 19 IS 2 BP 105 EP 111 DI 10.1002/syn.890190206 PG 7 WC Neurosciences SC Neurosciences & Neurology GA QE645 UT WOS:A1995QE64500005 PM 7725239 ER PT J AU EASTPALMER, J SZKUDLINSKI, MW LEE, J THOTAKURA, NR WEINTRAUB, BD AF EASTPALMER, J SZKUDLINSKI, MW LEE, J THOTAKURA, NR WEINTRAUB, BD TI A NOVEL, NONRADIOACTIVE IN-VIVO BIOASSAY OF THYROTROPIN (TSH) SO THYROID LA English DT Article ID HAMSTER OVARY CELLS; METABOLIC-CLEARANCE; BIOACTIVITY; INVITRO; HORMONE AB A new and simple in vivo bioassay suitable for routine testing of pituitary and recombinant TSH preparations was developed, Male Albino Swiss CF-1 mice were given T-3 in their drinking water to suppress endogenous TSH, T-3, 3.0 mu g/mL, given to mice for a period of 4 days decreased plasma total T-4 (TT4) level to less than 10% of the nonsuppressed (control) level, Various doses of exogenous pituitary and recombinant TSH preparations were injected intraperitoneally and blood samples were obtained from the orbital sinus 6 h later, The TT4 level, measured by radioimmunoassay, served as the assay end-point, The assay required injection of approximately 3.0 mu of pituitary human TSH (phTSH), 1.0 mu g recombinant human TSH (rhTSH), 0.2 mu g bovine TSH (bTSH), and 0.1 mu g rat TSH (rTSH) to attain half-maximal response. The maximal level of TT4 after TSH stimulation was similar to that observed in normal, nonsuppressed mice. The procedure developed is relatively easy to perform, economical, and, unlike earlier TSH bioassays, does not require the use of radionuclides, This bioassay showed acceptable sensitivity and reliability in structure-function studies of pituitary TSH from different species as well as rhTSH. C1 NIDDKD,MOLEC & CELLULAR ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 26 TC 39 Z9 39 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1050-7256 J9 THYROID JI Thyroid PD FEB PY 1995 VL 5 IS 1 BP 55 EP 59 DI 10.1089/thy.1995.5.55 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QK520 UT WOS:A1995QK52000011 PM 7787435 ER PT J AU BLANK, M BLANK, A KING, S YASHIKI, S KUWAYAMA, M FUJIYAMA, C GONGORA, D ZANINOVIC, V CRANSTON, B HANCHARD, B IMANISHI, T MANNS, A BLATTNER, WA TAJIMA, K HAYAMI, M FUJIYOSHI, T SONODA, S AF BLANK, M BLANK, A KING, S YASHIKI, S KUWAYAMA, M FUJIYAMA, C GONGORA, D ZANINOVIC, V CRANSTON, B HANCHARD, B IMANISHI, T MANNS, A BLATTNER, WA TAJIMA, K HAYAMI, M FUJIYOSHI, T SONODA, S TI DISTRIBUTION OF HLA AND HAPLOTYPES OF COLOMBIAN AND JAMAICAN BLACK POPULATIONS SO TISSUE ANTIGENS LA English DT Article DE COLOMBIAN BLACK; CARIBBEAN BLACK; GENETIC HETEROGENEITY; HLA HAPLOTYPES ID TROPICAL SPASTIC PARAPARESIS; CELL LEUKEMIA LYMPHOMA; PHYLOGENETIC TREES; HTLV-I; ANTIGENS AB To investigate the genetic background of the black populations of Colombia and Jamaica, we determined HLA types of 78 Colombian and 98 Jamaican blacks from 2 different socioeconomic groups (Jamaican #1 and Jamaican #2) and estimated the frequencies of HLA genes and haplotypes. A phylogenetic tree based on the HLA gene frequencies revealed that Jamaican #1 and Jamaican #2 were distinct from each other, Jamaican #1 being closely related to the Colombian blacks and the Jamaican #2 being closely related to Senegalese and Zairean populations. Three-locus HLA haplotypes of Colombian and Jamaican #1 blacks were an admixture between Africans and Caucasians or South American Indians, while Jamaican #2 blacks were relatively homogeneous and appeared to conserve African lineages. The major five-locus HLA haplotypes were not shared among Colombian, Jamaican #1 and Jamaican #2 blacks. These results indicated that the black populations of Colombia and Jamaica were originated from African blacks and admired variably with Caucasians and South American Indians to make genetic subpopulations in Colombia and Jamaica. C1 KAGOSHIMA UNIV,FAC MED,DEPT VIROL,KAGOSHIMA 890,JAPAN. UNIV VALLE,DIV CELL BIOL,SASAKAWA LAB,CALI,COLOMBIA. UNIV W INDIES,KINGSTON 7,JAMAICA. GUAPI REG HOSP,GUAPI,COLOMBIA. UNIV VALLE,DEPT CLIN NEUROL,CALI,COLOMBIA. NATL INST GENET,DNA RES CTR,SHIZUOKA,JAPAN. NIH,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. AICHI CANC CTR,RES INST,DIV EPIDEMIOL,NAGOYA,AICHI 464,JAPAN. KYOTO UNIV,INST VIRUS RES,KYOTO,JAPAN. NR 25 TC 18 Z9 18 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD FEB PY 1995 VL 45 IS 2 BP 111 EP 116 DI 10.1111/j.1399-0039.1995.tb02426.x PG 6 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA QJ662 UT WOS:A1995QJ66200005 PM 7792756 ER PT J AU SHIRAISHI, N HOCHADEL, JF COOGAN, TP KOROPATNICK, J WAALKES, MP AF SHIRAISHI, N HOCHADEL, JF COOGAN, TP KOROPATNICK, J WAALKES, MP TI SENSITIVITY TO CADMIUM-INDUCED GENOTOXICITY IN RAT TESTICULAR CELLS IS ASSOCIATED WITH MINIMAL EXPRESSION OF THE METALLOTHIONEIN GENE SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID DIETARY ZINC-DEFICIENCY; WISTAR CRL-(WI)BR RATS; DOSE-RESPONSE ANALYSIS; BINDING PROTEINS; MAMMALIAN-CELLS; TUMOR-INDUCTION; INJECTION SITE; TESTES; CARCINOGENESIS; PROSTATE AB Cadmium is a carcinogenic metal. Although the mechanism of tumor induction is unknown, DNA/metal interactions may be involved. Metallothionein can protect against cadmium toxicity and in our previous work it was shown to reduce cadmium genotoxicity in cultured cells. To extend these results, the genotoxicity of cadmium was studied in R2C cells, a rat testicular Leydig cell line. The R2C cells were very sensitive to cadmium-induced single-strand DNA damage (SSD), as measured by alkaline elution. SSD occurred in R2C cells after treatment with 25 and 50 mu M CdCl2 for 2 hr. Prior work showed other cells required much higher levels of cadmium (similar to 500 mu M) to induce genotoxicity. The genotoxic levels of cadmium (25-50 mu M) were not cytotoxic in R2C cells as assessed by a metabolic activity (MTT) assay. Pretreatment of R2C cells with a low cadmium dose (2 mu M, 24 hr) had no effect on cadmium-induced SSD, in contrast to prior work in other cells where such pretreatments reduced SSD through metallothionein gene activation. In fact, cadmium or zinc treatments resulted in little or no increase in metallothionein gene expression in R2C cells as determined by Northern blot analysis for metallothionein mRNA using cDNA or oligonucleotide probes and radioimmunoassay for metallothionein protein production. Basal metallothionein mRNA was essentially nondetectable. Induction of a cadmium-binding protein in R2C cells did occur, as determined by Cd-heme assay, but did not induce tolerance to SSD. In vivo, the Leydig cell is a target for cadmium carcinogenicity and its cadmium-binding protein is thought not to be a true metallothionein. These results indicate that R2C cells are sensitive to cadmium-induced genotoxicity and that this sensitivity is associated with minimal expression of the metallothionein gene. (C) 1995 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,DIV CANC ETIOL,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. UNIV WESTERN ONTARIO,LONDON REG CANC CTR,LONDON,ON,CANADA. NR 48 TC 48 Z9 50 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD FEB PY 1995 VL 130 IS 2 BP 229 EP 236 DI 10.1006/taap.1995.1028 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA QK939 UT WOS:A1995QK93900006 PM 7871536 ER PT J AU HENGEN, PN AF HENGEN, PN TI METHODS AND REAGENTS - CLONING PCR PRODUCTS USING T-VECTORS SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article 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 compares some of the commercially available vectors for cloning PCR fragments and discusses some of the problems encountered with them. 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 4 TC 9 Z9 10 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD FEB PY 1995 VL 20 IS 2 BP 85 EP 86 DI 10.1016/S0968-0004(00)88964-1 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QF771 UT WOS:A1995QF77100011 PM 7701569 ER PT J AU QUEZADO, ZMN BANKS, SM NATANSON, C AF QUEZADO, ZMN BANKS, SM NATANSON, C TI NEW STRATEGIES FOR COMBATING SEPSIS - THE MAGIC BULLETS MISSED THE MARK...BUT THE SEARCH CONTINUES SO TRENDS IN BIOTECHNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; CONTROLLED CLINICAL-TRIAL; GRAM-NEGATIVE BACTEREMIA; MONOCLONAL IGM ANTIBODY; HUMAN SEPTIC SHOCK; LIPID-A; CYCLOOXYGENASE INHIBITION; FACTOR CHALLENGES; FACTOR CACHECTIN; FACTOR-ALPHA AB Despite the high expectations of scientists and industry, multiple clinical trials of anti-endotoxin- and anti-cytokine-based therapies for sepsis have failed to demonstrate benefit. Indeed, in some cases, the agents used were actually harmful to patients. In retrospect, perhaps the therapeutic premises on which these therapies were based were flawed. In the future, a better understanding of sepsis should lead to the development of accurate laboratory and clinical predictors that will identify when, and which, patients can benefit from a given therapy. Much has been learned from the efforts of industry and academia and, hopefully, the search for new therapies for this lethal syndrome will continue. RP QUEZADO, ZMN (reprint author), NIH,DEPT CRIT CARE MED,BETHESDA,MD 20892, USA. RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 NR 57 TC 42 Z9 42 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD FEB PY 1995 VL 13 IS 2 BP 56 EP 63 DI 10.1016/S0167-7799(00)88906-4 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA QK235 UT WOS:A1995QK23500006 PM 7765996 ER PT J AU ROSENTHAL, JP KOTANEN, P AF ROSENTHAL, JP KOTANEN, P TI SYNTHESIZING PLANT TOLERANCE AND AVOIDANCE OF HERBIVORY - DO ECOLOGISTS RISK REINVENTING THE WHEEL - REPLY SO TRENDS IN ECOLOGY & EVOLUTION LA English DT Letter C1 UNIV CALIF BERKELEY,DEPT INTEGRAT BIOL,BERKELEY,CA 94720. RP ROSENTHAL, JP (reprint author), NIH,FOGARTY INT CTR,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0169-5347 J9 TRENDS ECOL EVOL JI Trends Ecol. Evol. PD FEB PY 1995 VL 10 IS 2 BP 82 EP 82 DI 10.1016/S0169-5347(00)88983-1 PG 1 WC Ecology; Evolutionary Biology; Genetics & Heredity SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics & Heredity GA QG114 UT WOS:A1995QG11400012 PM 21236961 ER PT J AU MASON, JM BIESSMANN, H AF MASON, JM BIESSMANN, H TI THE UNUSUAL TELOMERES OF DROSOPHILA SO TRENDS IN GENETICS LA English DT Review ID BROKEN CHROMOSOME ENDS; DNA-SEQUENCES; HET-A; MELANOGASTER; HETEROCHROMATIN; ELEMENT; GENE; RECOMBINATION; PATHWAY; REGIONS AB The telomeres of most eukaryotes contain short, simple repeats that are highly conserved. Drosophila, on the other hand does not have such sequences, but carries at the ends of its chromosomes one or more LINE-like retrotransposable elements. Instead of elongation by telomerase, incomplete DNA replication at the termini of Drosophila chromosomes is counterbalanced by transposition of these elements at high frequency specifically to the termini. These transposable elements are not responsible for distinguishing telomeric ends in Drosophila from broken chromosome ends; the structure performing this function is not yet known. Proximal to the terminal army of transposable elements are regions of tandem repeats that are structurally, and probably functionally, analogous to the subterminal regions in other eukaryotes. C1 UNIV CALIF IRVINE,CTR DEV BIOL,IRVINE,CA 92717. RP MASON, JM (reprint author), NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709, USA. FU NIGMS NIH HHS [GM46211] NR 30 TC 156 Z9 160 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD FEB PY 1995 VL 11 IS 2 BP 58 EP 62 DI 10.1016/S0168-9525(00)88998-2 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA QG424 UT WOS:A1995QG42400009 PM 7716808 ER PT J AU AXELROD, J AF AXELROD, J TI PHOSPHOLIPASE A(2) AND G-PROTEINS SO TRENDS IN NEUROSCIENCES LA English DT Article ID GTP-BINDING PROTEINS; ROD OUTER SEGMENTS; ARACHIDONIC-ACID; THYROID-CELLS; ACTIVATION; STIMULATION; INHIBITION; RELEASE; SUBUNIT RP AXELROD, J (reprint author), NCI,DEPT HLTH & HUMAN SERV,BETHESDA,MD 20892, USA. NR 17 TC 35 Z9 35 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD FEB PY 1995 VL 18 IS 2 BP 64 EP 65 PG 2 WC Neurosciences SC Neurosciences & Neurology GA QD402 UT WOS:A1995QD40200011 PM 7537411 ER PT J AU SPIVAK, CE AF SPIVAK, CE TI CORRELATIONS AMONG HILL PARAMETERS REFLECT MODELS OF ACTIVATING LIGAND-GATED ION CHANNELS SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Article ID GABA AB Molecular biology has contributed a concept, novel in pharmacology, in which the receptor is an independent variable. Site-directed mutagenesis of ligand-gated ion channels is now commonplace. The mutant receptor is usually characterized by the Hill parameters that describe concentration-response curves from transfected, voltage-clamped cells. In this article, Charles Spivak describes how to convert parameters for realistic models of channel activation into Hill parameters. Correlations among the Hill parameters that the models enforce can be useful in tentatively assigning a physiological function to the mutation site. RP SPIVAK, CE (reprint author), NIDA,DIV INTRAMURAL RES,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 7 TC 11 Z9 11 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD FEB PY 1995 VL 16 IS 2 BP 39 EP 42 DI 10.1016/S0165-6147(00)88976-2 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QP892 UT WOS:A1995QP89200004 PM 7762081 ER PT J AU GORSE, GJ ROGERS, JH PERRY, JE NEWMAN, FK FREY, SE PATEL, GB BELSHE, RB SCHWARTZ, DH CLEMENTS, ML KEEFER, M DOLIN, R MCELRATH, J COREY, L GRAHAM, BS WRIGHT, PF STABLEIN, DM MATTHEWS, TJ BOLOGNESI, D MESTECKY, J WALKER, MC FAST, PE AF GORSE, GJ ROGERS, JH PERRY, JE NEWMAN, FK FREY, SE PATEL, GB BELSHE, RB SCHWARTZ, DH CLEMENTS, ML KEEFER, M DOLIN, R MCELRATH, J COREY, L GRAHAM, BS WRIGHT, PF STABLEIN, DM MATTHEWS, TJ BOLOGNESI, D MESTECKY, J WALKER, MC FAST, PE TI HIV-1 RECOMBINANT GP160 VACCINE-INDUCED ANTIBODIES IN SERUM AND SALIVA SO VACCINE LA English DT Article DE HIV-1 VACCINE; SALIVA ANTIBODIES; IMMUNOGENICITY; ANTI-ENVELOPE GLYCOPROTEIN ID IMMUNODEFICIENCY-VIRUS TYPE-1; DEFENSE-MECHANISMS; IMMUNOGENICITY; IMMUNIZATION; SAFETY; TRIAL; RISK AB As part of a phase I safety and immunogenicity trial of a vaccinia-expressed HIV-1 recombinant gp160 (rgp160) candidate vaccine, we measured serum and saliva antibody responses in low risk, uninfected volunteers. Six healthy adult volunteers received 50 mu g doses of rgp160 vaccine adjuvanted in alum and deoxycholate at months 0, 1, 6, and 12. A 200 mu g rgp160 immunization was given to four volunteers at 18 months. The vaccine induced anti-envelope glycoprotein IgG and IgA serum antibodies in all six volunteers. Saliva antibodies to envelope glycoprotein appeared in some volunteers at certain timepoints. Three volunteers appeared to transiently develop vaccine-induced secretory IgA antibody to envelope glycoprotein in whole saliva. C1 DEPT VET AFFAIRS MED CTR,ST LOUIS,MO. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. UNIV ROCHESTER,ROCHESTER,NY 14627. GEORGE WASHINGTON UNIV,WASHINGTON,DC. VANDERBILT UNIV,NASHVILLE,TN 37240. EMMES CORP,POTOMAC,MD. DUKE UNIV,DURHAM,NC 27706. UNIV ALABAMA,BIRMINGHAM,AL. NIAID,DIV AIDS,BETHESDA,MD 20892. RP GORSE, GJ (reprint author), ST LOUIS UNIV,CTR HLTH SCI,DIV INFECT DIS,3635 VISTA AVE FDT-8N,POB 15250,ST LOUIS,MO 63110, USA. FU NIAID NIH HHS [N01-AI-05064] NR 24 TC 12 Z9 12 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA LINACRE HOUSE JORDAN HILL, OXFORD, OXON, ENGLAND OX2 8DP SN 0264-410X J9 VACCINE JI Vaccine PD FEB PY 1995 VL 13 IS 2 BP 209 EP 214 DI 10.1016/0264-410X(95)93138-Y PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA QK473 UT WOS:A1995QK47300013 PM 7625118 ER PT J AU ANDRADE, ZA CHEEVER, AW AF ANDRADE, ZA CHEEVER, AW TI CHRONIC HEPATITIS IN EXPERIMENTAL SCHISTOSOMIASIS SO VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY LA English DT Article DE EXPERIMENTAL SCHISTOSOMIASIS; SCHISTOSOMAL HEPATITIS; CHRONIC HEPATITIS; HEPATIC SCHISTOSOMIASIS ID B VIRUS-INFECTION; HEPATOSPLENIC SCHISTOSOMIASIS; MANSONI; SUDAN AB Histological features of chronic active and chronic persistent hepatitis were observed in mice, rabbits and non-human primates infected with either Schistosoma mansoni and Schistosoma jayonicum. In early infection hepatitis appeared as a reactive change due to liver damage caused by the deposition of schistosome eggs, but portal and septal cellular infiltrations tended to remain long after parasite aggression had diminished or disappeared, either spontaneously with time or after chemotherapy. In rabbits, and to a lesser degree in monkeys, a picture of chronic active hepatitis was present, with evolution to cirrhosis in the former. The experimental findings indicate that schistosomiasis has the potential to induce chronic hepatitis and suggest that the current as sumption that chronic hepatitis seen in humans with schistosomiasis is always due to concomitant viral infection should be reviewed. C1 NIH,PARASIT DIS LAB,BETHESDA,MD 20892. GONCALO MONIZ RES CTR,BR-40295001 SALVADOR,BA,BRAZIL. NR 26 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. Int. J. Pathol. PD FEB PY 1995 VL 426 IS 1 BP 87 EP 93 PG 7 WC Pathology SC Pathology GA QP647 UT WOS:A1995QP64700012 PM 7704327 ER PT J AU COHEN, JI SEIDEL, KE AF COHEN, JI SEIDEL, KE TI VARICELLA-ZOSTER VIRUS OPEN READING FRAME-1 ENCODES A MEMBRANE-PROTEIN THAT IS DISPENSABLE FOR GROWTH OF VZV IN-VITRO SO VIROLOGY LA English DT Article ID COMPLETE DNA-SEQUENCE; THYMIDYLATE SYNTHETASE; EXPRESSION; GENERATION; MUTANTS; GENOME; TYPE-1 AB Varicella-zoster virus (VZV) encodes 69 unique open reading frames, 5 of which do not have herpes simplex virus type 1 (HSV-1) homologs. One of the 5, ORF1, is predicted to encode a protein of 108 amino acids. We identified a 470-base RNA corresponding to ORF1. To determine whether ORF1 encodes a protein, an 11-amino-acid epitope was inserted in frame after the ninth codon of the ORF1 open reading frame. A recombinant virus carrying this epitope expressed a protein that was immunoprecipitated with monoclonal antibody to the epitope. The ORF1 protein was detected in the membrane of infected cells. The size of ORF1 protein expressed in VZV-infected cells was slightly larger than the size expressed by translation in vitro, suggesting that the protein may undergo post-translational modification in infected cells. Insertion of stop codons immediately before the epitope in the ORF1 gene resulted in a recombinant virus that did not express ORF1 protein and that was not growth impaired in cell culture. Thus, ORF1 encodes a protein that localizes to the membrane of VZV-infected cells and that is dispensable for virus growth in vitro. (C) 1995 Academic Press, Inc. RP COHEN, JI (reprint author), NIAID,CLIN INVEST LAB,MED VIROL SECT,BETHESDA,MD 20892, USA. NR 18 TC 24 Z9 24 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD FEB 1 PY 1995 VL 206 IS 2 BP 835 EP 842 DI 10.1006/viro.1995.1006 PG 8 WC Virology SC Virology GA QH225 UT WOS:A1995QH22500006 PM 7856096 ER PT J AU RAMSEYEWING, A MOSS, B AF RAMSEYEWING, A MOSS, B TI RESTRICTION OF VACCINIA VIRUS-REPLICATION IN CHO CELLS OCCURS AT THE STAGE OF VIRAL INTERMEDIATE PROTEIN-SYNTHESIS SO VIROLOGY LA English DT Article ID HAMSTER OVARY CELLS; HOST RANGE RESTRICTION; MUTATIONAL ANALYSIS; TRANSCRIPTION FACTOR; INVITRO TRANSLATION; GENE-EXPRESSION; MESSENGER-RNA; SEQUENCE; MUTANT; PROMOTERS AB Vaccinia Virus (VV) and cowpox virus (CPV) differ in their abilities to replicate in Chinese hamster ovary (CHO) cells because VV has a disrupted host range (hr) gene. To facilitate an examination of the molecular events associated with abortive infection of CHO cells with W, we constructed two sets of recombinant viruses that contain a viral early promoter regulating the cat gene encoding chloramphenicol acetyltransferase and viral intermediate or late promoters regulating the lacZ gene encoding beta-galactosidase. The first set has the disrupted hr gene and the second set has the intact CPV homolog, allowing replication in CHO cells. Reporter chloramphenicol acetyltransferase and beta-galactosidase assays demonstrated that early gene expression was unperturbed, whereas intermediate and late gene expression were severely inhibited under abortive conditions. Metabolic labeling studies confirmed the absence of viral late protein synthesis. The accumulation of viral DNA under abortive conditions was consistent with the synthesis of viral early proteins and established that inhibition of late protein synthesis was not primarily due to a replicative block. Analysis of steady slate levels of viral mRNAs revealed substantial quantities of early and intermediate species but only very small amounts of tate mRNAs under nonpermissive conditions. Despite the presence of viral intermediate mRNAs, the corresponding intermediate proteins, which function as late transcription factors, were not detected by immunoprecipitation of lysates from metabolically labeled infected CHO cells. Furthermore, when expression of lacZ was regulated by an intermediate promoter, no beta-galactosidase was detected even though lacZ transcripts were present Thus, the abortive phenotype in CHO cells can be explained by a block to translation of intermediate mRNAs which prevents the synthesis of late transcription factors. (C) 1995 academic Press, Inc. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NR 44 TC 43 Z9 43 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD FEB 1 PY 1995 VL 206 IS 2 BP 984 EP 993 DI 10.1006/viro.1995.1021 PG 10 WC Virology SC Virology GA QH225 UT WOS:A1995QH22500021 PM 7856109 ER PT J AU SANDER, M HUANG, SM AF SANDER, M HUANG, SM TI CHARACTERIZATION OF THE NUCLEASE ACTIVITY OF DROSOPHILA RRPL ON PHOSPHOGLYCOLATE-MODIFIED AND PHOSPHATE-MODIFIED DNA 3'-TERMINI SO BIOCHEMISTRY LA English DT Article ID APURINIC APYRIMIDINIC ENDONUCLEASE; ESCHERICHIA-COLI; REPAIR ENZYMES; EXONUCLEASE; IV; DEOXYRIBOSE; MECHANISM; BLEOMYCIN; HOMOLOGY; PROTEIN AB Drosophila Rrp1 includes a carboxy-terminal region homologous to Escherichia coli exonuclease III which is sufficient to repair both oxidative and alkylation damage to DNA. An apurinic/apyrimidinic endonuclease activity intrinsic to Rrp1 was characterized previously. In this work, the 3'-phosphodiesterase and 3'-phosphatase activities of Rrp1 are demonstrated and characterized. Phosphoglycolate- and phosphate-modified DNA 3'-termini are formed by oxygen radical induced DNA cleavage. To demonstrate the 3'-phosphodiesterase activity of Rrp1, a 3'-phosphoglycolate-terminated oligonucleotide substrate was generated by site-specific cleavage of a unique GpC dinucleotide by iron(II) bleomycin. Removal of the terminal phosphoglycolate is detected by mobility shift on a DNA sequencing gel. Rrp1 cleaves the phosphoglycolate and releases a product with a 3'-hydroxyl terminus. Phosphoglycolate is removed more readily than the 3'-terminal dGMP residue. Rrp1 phosphodiesterase activity is not inhibited by 120 mM NaCl, while the 3'-exonuclease is reduced 25-fold. Using a 3'-phosphate-terminated oligonucleotide, the phosphatase activity of Rrp1 is at least 25-fold lower than its phosphodiesterase or apurinic endonuclease, and 56-fold lower than exonuclease III activity on the identical substrate. Rrp1 3'-phosphatase is reduced 25-fold by 80 mM NaCl. These results were confirmed using an assay that measures the ability of Rrp1 to stimulate DNA synthesis on circular DNA substrates nicked by various DNA damage treatments. In that assay, Rrp1 poorly repairs 3'-phosphate-terminated nicks introduced by micrococcal nuclease. The significance of these enzymatic properties for the biological role of Rrp1 is discussed. RP SANDER, M (reprint author), NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709, USA. NR 38 TC 22 Z9 23 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 31 PY 1995 VL 34 IS 4 BP 1267 EP 1274 DI 10.1021/bi00004a021 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QE538 UT WOS:A1995QE53800021 PM 7530050 ER PT J AU SCHURTER, EJ YEH, HJC SAYER, JM LAKSHMAN, MK YAGI, H JERINA, DM GORENSTEIN, DG AF SCHURTER, EJ YEH, HJC SAYER, JM LAKSHMAN, MK YAGI, H JERINA, DM GORENSTEIN, DG TI NMR SOLUTION STRUCTURE OF A NONANUCLEOTIDE DUPLEX WITH A DG MISMATCH OPPOSITE A 10R ADDUCT DERIVED FROM TRANS ADDITION OF A DEOXYADENOSINE N-6-AMINO GROUP TO ((-))-(7S,8R,9R,10S)-7,8-DIHYDROXY-9,10-EPOXY-7,8,9,10-TETRAHYDROBENZO[A ]PYRENE SO BIOCHEMISTRY LA English DT Article ID COVALENT NUCLEOSIDE ADDUCTS; RELAXATION MATRIX APPROACH; DOSE-DEPENDENT DIFFERENCES; DIOL EPOXIDE; SOLUTION CONFORMATION; DNA-ADDUCTS; BENZOPYRENE; CARCINOGEN; 9,10-EPOXIDES; ENANTIOMER AB A nonanucleotide in which (-)-(7S,8R,9R,10S)-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (7-hydroxy group and epoxide oxygen are trans) is covalently bended to the exocyclic N-6-amino group of deoxyadenosine through trans addition at C10 of the epoxide (10R adduct) has been synthesized. The modified oligonucleotide d(GGTCA*CGAG) was incorporated into the duplex d(GGTCA*CGAG).d(CTCGGGACC), containing a dG mismatch opposite the modified base (dA*). Proton assignments for the solution structure of the duplex containing the 10R adduct were made using 2D TOCSY and NOESY NMR spectra. The complete hybrid relaxation matrix program, MORASS2.0, was used to generate NOESY distance constraints for iterative refinement using distance-restrained molecular dynamics calculations with AMBER4.0. The iteratively refined structure showed the hydrocarbon intercalated from the major groove immediately below the dC(4)-dG(15) base pair and oriented toward the 5'-end of the modified strand. The modified dA is in an anti configuration, with the dG of the GA mismatch turned out into the major groove. Chemical shifts of the hydrocarbon protons and unusual chemical shifts of sugar protons were accounted for by this orientation of the adduct. The information available currently provides the foundation for the rational explanation of observed benzo[a]pyrene (BaP) structures and predictions for other BaP dG and dA adducts. C1 PURDUE UNIV,DEPT CHEM,W LAFAYETTE,IN 47907. NIDDKD,BETHESDA,MD 20892. FU NCI NIH HHS [CA09634]; NIAID NIH HHS [AI27744] NR 35 TC 77 Z9 77 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 31 PY 1995 VL 34 IS 4 BP 1364 EP 1375 DI 10.1021/bi00004a031 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QE538 UT WOS:A1995QE53800031 PM 7827084 ER PT J AU HILBERT, DM SHEN, MY RAPP, UR RUDIKOFF, S AF HILBERT, DM SHEN, MY RAPP, UR RUDIKOFF, S TI T-CELLS INDUCE TERMINAL DIFFERENTIATION OF TRANSFORMED B-CELLS TO MATURE PLASMA-CELL TUMORS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MULTIPLE-MYELOMA PATIENTS; MONOCLONAL LYMPHOCYTES-B; BONE-MARROW; PERIPHERAL-BLOOD; MURINE PLASMACYTOMAGENESIS; RAPID INDUCTION; LINEAGE CELLS; V-ABL; C-MYC; MICE AB Major interest in the analysis of mature plasma cell neoplasias of mice and humans has focused on identification of precursor cells that give rise to mature malignant plasma cells. Although several laboratories have recently suggested that such cells are present in the granulomas of pristane-treated mice and the bone marrow of some multiple myeloma patients, the in vivo cellular interactions required for their differentiation into mature plasma cell tumors remains unclear. Given the extensive interactions of peripheral T cells and normal B cells, we assessed the potential role of T cells in plasma-cell tumor development, by using a myc, raf-containing retrovirus, J3V1, to induce plasmacytomas in normal BALB/c mice, T-cell-deficient nude mice, and T-cell-reconstituted nude mice. The B-lineage tumors arising in normal BALB/c mice were uniformly mature plasmacytomas, most of which secreted immunoglobulin. In contrast, nude mice yielded predominantly non-immunoglobulin-secreting B-cell lymphomas with a phenotype characteristic of peripheral B cells. T-cell reconstitution of nude mice prior to tumor induction resulted in a shift from B-cell lymphomas to plasmacytomas. These results imply that transformation can occur prior to terminal differentiation of B cells and that such transformed cells can be driven to terminal differentiation by peripheral T cells. These findings further suggest that, in human multiple myeloma, the ability of T cells to influence the differentiation state of transformed B cells may provide a mechanism by which malignant plasma cells found in the bone marrow could arise from clonotypically related less-mature B cells found in both the bone marrow and periphery. C1 NCI,FREDERICK CANC RES CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. RP HILBERT, DM (reprint author), NCI,GENET LAB,BLDG 37,BETHESDA,MD 20892, USA. NR 50 TC 40 Z9 43 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 31 PY 1995 VL 92 IS 3 BP 649 EP 653 DI 10.1073/pnas.92.3.649 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QF185 UT WOS:A1995QF18500002 PM 7846031 ER PT J AU POKHOLOK, DK MAROULAKOU, IG KUPRASH, DV ALIMZHANOV, MB KOZLOV, SV NOVOBRANTSEVA, TI TURETSKAYA, RL GREEN, JE NEDOSPASOV, SA AF POKHOLOK, DK MAROULAKOU, IG KUPRASH, DV ALIMZHANOV, MB KOZLOV, SV NOVOBRANTSEVA, TI TURETSKAYA, RL GREEN, JE NEDOSPASOV, SA TI CLONING AND EXPRESSION ANALYSIS OF THE MURINE LYMPHOTOXIN BETA-GENE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TUMOR-NECROSIS-FACTOR; MAJOR HISTOCOMPATIBILITY COMPLEX; FACTOR TNF-ALPHA; TRANSCRIPTION FACTORS; NUCLEOTIDE-SEQUENCE; KAPPA-B; MOUSE; INFECTION; CELLS; MONOCYTOGENES AB Tumor necrosis factor alpha (TNF-alpha) and soluble lymphotoxin (LT) (also called LT-alpha or TNF-beta) are cytokines with similar biological activities that are encoded by related and closely linked genes. TNF-alpha, a mediator of the inflammatory response, exists in soluble and transmembrane forms. LT-alpha can be secreted or retained at the cell surface by binding to a 33-kDa transmembrane subunit, LT-beta. The recently cloned human LT-beta gene encodes another TNF family member and is linked to the TNF/LT locus within the major histocompatibility complex locus. The cell surface LT is a heterotrimer consisting of LT-alpha and LT-beta, whose physiological function is not yet clearly defined. We now report the sequence analysis of the genomic region and cDNA of murine LT-beta gene, which is closely associated with the TNF-alpha and LT-alpha genes within the murine major histocompatibility complex locus. Unlike the TNF-alpha, LT-alpha, and human LT-beta genes, which contain four exons, the murine LT-beta contains three exons and encodes a 244-amino acid polypeptide with a 66-amino acid insert that is absent from the human homologue. In situ hybridization demonstrates constitutive expression of LT-beta in lymphoid and hematopoietic tissues. LT-beta transcription is maximal in the thymic medulla and in splenic white pulp. LT-beta mRNA is also detected in the skin and in specific regions of the brain. The LT-beta promoter region contains putative Ets-binding sites, suggesting that the expression of LT-beta may be regulated in part by Ets transcription factors whose pattern of lymphoid expression overlaps that of LT-beta. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,MOLEC IMMUNOREGULAT BIOL RESPONSE LAB,MODIFIERS PORGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,MOLEC ONCOL LAB,FREDERICK,MD 21702. VA ENGELHARDT MOLEC BIOL INST,MOSCOW 117984,RUSSIA. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Kuprash, Dmitry/O-4899-2015; Nedospasov, Sergei/Q-7319-2016 OI Kuprash, Dmitry/0000-0002-1488-4148; NR 41 TC 51 Z9 52 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 31 PY 1995 VL 92 IS 3 BP 674 EP 678 DI 10.1073/pnas.92.3.674 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QF185 UT WOS:A1995QF18500007 PM 7846035 ER PT J AU WEISSMAN, D LI, YX ANANWORANICH, J ZHOU, LJ ADELSBERGER, J TEDDER, TF BASELER, M FAUCI, AS AF WEISSMAN, D LI, YX ANANWORANICH, J ZHOU, LJ ADELSBERGER, J TEDDER, TF BASELER, M FAUCI, AS TI 3 POPULATIONS OF CELLS WITH DENDRITIC MORPHOLOGY EXIST IN PERIPHERAL-BLOOD, ONLY ONE OF WHICH IS INFECTABLE WITH HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE INFECTION; DENDRITIC CELL; PRECURSOR ID CD4+ T-CELLS; GM-CSF; INFECTION; REPLICATION; MACROPHAGES; COMPETENT; TNF AB Conflicting data have been reported with regard to the infectability, dysfunction, and depletion of dendritic cells (DCs) in human immunodeficiency virus (HIV) disease. These discrepancies could potentially be explained by the existence of multiple subsets of cells with dendritic morphology in peripheral blood. The isolation of DCs in humans is accomplished through negative selection until a morphologically pure population is obtained. Recently, DC precursors purified from peripheral blood by negative selection have been observed to develop into functionally and morphologically mature DCs. In this report we identify three populations of cells in peripheral blood that have or can develop a dendritic morphology. The first population, when allowed to mature in culture, develops a dendritic morphology and gains the expression of HB15, a marker of DCs in blood, thymus, skin, and lymphoid organs. The second population expresses HB15 and has the phenotypic and morphologic characteristics of mature DCs. The third population is morphologically very similar to mature DCs but does not share the same T-cell-stimulatory activity and is the only population that is infectable with HIV. Understanding the heterogeneity of cells of dendritic lineage and/or morphology in the peripheral blood will aid in understanding their role as antigen-presenting cells in general and as potential participants in the immunopathogenesis of HIV disease. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK,MD 21702. RP WEISSMAN, D (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM 6A02,BETHESDA,MD 20892, USA. NR 19 TC 176 Z9 176 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 31 PY 1995 VL 92 IS 3 BP 826 EP 830 DI 10.1073/pnas.92.3.826 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QF185 UT WOS:A1995QF18500038 PM 7846060 ER PT J AU HYDE, TM EGAN, MF BROWN, RJ WEINBERGER, DR KLEINMAN, JE AF HYDE, TM EGAN, MF BROWN, RJ WEINBERGER, DR KLEINMAN, JE TI DIURNAL-VARIATION IN TARDIVE-DYSKINESIA SO PSYCHIATRY RESEARCH LA English DT Article DE SCHIZOPHRENIA; ABNORMAL INVOLUNTARY MOVEMENT SCALE; HALOPERIDOL; SIDE EFFECTS ID PHYSIOLOGICAL TREMOR; CIRCADIAN VARIATION; HOMOVANILLIC-ACID; RAT-BRAIN; DOPAMINE; METABOLISM; STRIATUM; RHYTHMS AB Tardive dyskinesia (TD) is a common movement disorder that is associated with chronic neuroleptic exposure. To better characterize the clinical aspects of TD, we investigated the diurnal pattern of involuntary movements by blindly rating videotaped examinations of patients from the morning shortly after awakening and later in the same afternoon. In 10 patients, average TD ratings were worse in the afternoon than in the morning, especially in the case of limb-trunk dyskinesias. These findings suggest that it is important to rate patients at the same time of day in TD studies. Moreover, patients should be evaluated at least several hours after awakening. C1 ST ELIZABETH HOSP,NIMH,NEUROSCI RES CTR ST ELIZABETHS,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. ST ELIZABETH HOSP,DEPT PSYCHIAT,WASHINGTON,DC 20032. RP HYDE, TM (reprint author), ST ELIZABETH HOSP,NIMH,NEUROSCI RES CTR ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032, USA. NR 26 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD JAN 31 PY 1995 VL 56 IS 1 BP 53 EP 57 DI 10.1016/0165-1781(94)02662-3 PG 5 WC Psychiatry SC Psychiatry GA QQ292 UT WOS:A1995QQ29200007 PM 7792342 ER PT J AU GELLERT, M MCBLANE, JF AF GELLERT, M MCBLANE, JF TI STEPS ALONG THE PATHWAY OF V(D)J RECOMBINATION SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES LA English DT Article ID T-CELL RECEPTOR; STRAND BREAK REPAIR; COMBINED IMMUNE-DEFICIENCY; BROKEN DNA-MOLECULES; SCID MUTATION; JUNCTIONAL SEQUENCES; GENE REARRANGEMENT; SIGNAL SEQUENCES; MOUSE THYMOCYTES; CODING SEGMENTS AB The mechanism of lymphoid-specific gene rearrangement (V(D)J recombination) is discussed, with a focus on the existence of broken DNA intermediates. Older evidence in support of this idea includes the sequence alterations at the recombined junctions and the presence of aberrant recombinants. More recently, broken DNA molecules have been directly detected in recombinationally active cells. The signal sequence ends have normal blunt-ended DNA breaks, but the coding ends have a hairpin (self-joined) structure that provides an explanation for the self-complementary P nucleotide insertions often found after V(D)J joining in the antigen receptor genes. RP GELLERT, M (reprint author), NIDDK,MOLEC BIOL LAB,BLDG 5,ROOM 241,BETHESDA,MD 20892, USA. NR 35 TC 6 Z9 6 U1 0 U2 0 PU ROYAL SOC LONDON PI LONDON PA 6 CARLTON HOUSE TERRACE, LONDON, ENGLAND SW1Y 5AG SN 0962-8436 J9 PHILOS T ROY SOC B JI Philos. Trans. R. Soc. Lond. Ser. B-Biol. Sci. PD JAN 30 PY 1995 VL 347 IS 1319 BP 43 EP 47 DI 10.1098/rstb.1995.0007 PG 5 WC Biology SC Life Sciences & Biomedicine - Other Topics GA QF004 UT WOS:A1995QF00400007 PM 7746852 ER PT J AU CHOW, WH MCLAUGHLIN, JK MANDEL, JS BLOT, WJ NIWA, S FRAUMENI, JF AF CHOW, WH MCLAUGHLIN, JK MANDEL, JS BLOT, WJ NIWA, S FRAUMENI, JF TI REPRODUCTIVE FACTORS AND THE RISK OF RENAL-CELL CANCER AMONG WOMEN SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID KIDNEY CANCER; CARCINOMA; HAMSTER; ESTROGEN; OBESITY AB In etiologic studies of renal cell carcinoma the role of reproductive variables and the use of exogenous hormones have not been well examined. In a population-based case-control study including 165 female cases and 227 controls, we assessed the risk of renal cell cancer associated with reproductive factors and use of oral contraceptives and menopausal hormones. Odds ratios were computed using logistic regression analyses. Risk was positively associated with number of births and inversely associated with age at first birth, with the largest increases in risk (more than 2-fold) among women with 5 or more births after age 25. After adjustment for age, smoking status, body mass index and age at first birth, women with 5 or more births had a 2-fold risk (OR = 2.2, 95% CI = 1.2-4.0) relative to those with I or 2 births. Age at first birth, however, was no longer a risk factor when the number of births was adjusted for. The association with parity was considerably stronger among women with a history of hypertension or above-median body mass index than among those without these conditions. In addition, risk was reduced among long-term oral contraceptive users but elevated among women who had had a hysterectomy or used menopausal hormones. Our findings suggest that reproductive factors, particularly the number of births, may play an etiologic role in renal cell cancer among women and deserve further study. (C) 1995 Wiley-Liss, Inc. C1 NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,ROCKVILLE,MD 20852. UNIV MINNESOTA,SCH PUBL HLTH,DIV ENVIRONM & OCCUPAT HLTH,MINNEAPOLIS,MN 55455. WESTAT CORP,ROCKVILLE,MD. NR 22 TC 35 Z9 35 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 27 PY 1995 VL 60 IS 3 BP 321 EP 324 DI 10.1002/ijc.2910600307 PG 4 WC Oncology SC Oncology GA QG235 UT WOS:A1995QG23500006 PM 7829237 ER PT J AU MELLEMKJAER, L OLSEN, JH FRISCH, M JOHANSEN, C GRIDLEY, G MCLAUGHLIN, JK AF MELLEMKJAER, L OLSEN, JH FRISCH, M JOHANSEN, C GRIDLEY, G MCLAUGHLIN, JK TI CANCER IN PATIENTS WITH ULCERATIVE-COLITIS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID INFLAMMATORY BOWEL-DISEASE; PRIMARY SCLEROSING CHOLANGITIS; COLORECTAL-CANCER; POPULATION; RISK; MALIGNANCY; DYSPLASIA AB A cohort of 5,546 ulcerative colitis patients was identified from the Danish Hospital Discharge Register for 1977-1989. Patients not included in the cohort comprised those with proctitis, those treated in outpatient clinics and those for whom follow-up was less than I year. The cohort was linked to the Danish Cancer Registry in order to assess the risks for colorectal and other cancers. The linkage revealed a significant increase in the number of colorectal cancers over that in the general population (RR = 1.8; n = 42; 95% CI = 1.3-2.4) with consistent relative risks during early and late follow-up. The relative risk was considerably higher among younger (20-39 years: RR = 22; n = 8; 95% CI = 9.7-44) than older patients (greater than or equal to 60 years: RR = 1.3; n = 25; 95% CI = 0.8-1.9), but the risk difference between patients and the general population was approximately constant across all ages. In addition, we observed a significant increase in the relative risk of hepatobiliary cancers (RR = 2.3; n = 9; 95% = 1.0-4.3) and a slight but significant increase in the relative risk of non-melanoma skin cancer (RR = 1.4; n = 37; 95% CI = 1.0-1.9). In summary, our population-based study confirms the increased risk of colorectal cancer among patients with ulcerative colitis and provides new leads suggesting that hepatobiliary cancer and non-melanoma skin cancer should be considered as possible sites for future patient monitoring. (C) 1995 Wiley-Liss, Inc. C1 STATENS SERUM INST,DANISH EPIDEMIOL SCI CTR,DK-2300 COPENHAGEN,DENMARK. NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. RP MELLEMKJAER, L (reprint author), DANISH CANC SOC,DIV CANC EPIDEMIOL,STRANDBLVD 49,DK-2100 COPENHAGEN O,DENMARK. RI Frisch, Morten/E-9206-2016 OI Frisch, Morten/0000-0002-3864-8860 FU NCI NIH HHS [N01-CP-85639-04] NR 25 TC 79 Z9 79 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 27 PY 1995 VL 60 IS 3 BP 330 EP 333 DI 10.1002/ijc.2910600309 PG 4 WC Oncology SC Oncology GA QG235 UT WOS:A1995QG23500008 PM 7829239 ER PT J AU MCCREDIE, M POMMER, W MCLAUGHLIN, JK STEWART, JH LINDBLAD, P MANDEL, JS MELLEMGAARD, A SCHLEHOFER, B NIWA, S AF MCCREDIE, M POMMER, W MCLAUGHLIN, JK STEWART, JH LINDBLAD, P MANDEL, JS MELLEMGAARD, A SCHLEHOFER, B NIWA, S TI INTERNATIONAL RENAL-CELL CANCER STUDY .2. ANALGESICS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID RISK-FACTORS; KIDNEY CANCER; PELVIS; PHENACETIN; CARCINOMA; BLADDER; PARACETAMOL; URETER; COHORT; WOMEN AB There has been concern about the role of analgesics in the development of renal-cell cancer, although a few studies have reported moderately elevated risks with regular or long-term use. In a large international case-control study of renal-cell cancer we examined, among other hypotheses, the effect of phenacetin-containing and of other types of analgesics: paracetamol (acetaminophen), salicylates (mainly aspirin) and pyrazolones (e.g., antipyrine or phenazone). Relative risks, adjusted for the effects of age, sex, body-mass index, tobacco smoking and study centre, were not significantly increased with intake of phenacetin, either when lifetime consumption was categorized at the level of greater than or equal to 0.1 kg or when subjects were subdivided further by amount. Nor were paracetamol, salicylates or pyrazolones linked with renal-cell cancer. No consistently increasing risks with consumption level was found. The lack of association was not altered by restricting analgesic use to that which occurred 5 or IO years before the defined ''cut-off'' date or when analysis was restricted to exclusive users of a particular type of analgesic. Neither was the risk influenced by the rate of consumption or whether the consumption had occurred at a young age. Our study provides clear evidence that aspirin is unrelated to renal-cell cancer risk, and our findings do not support the hypothesis that analgesics containing phenacetin or paracetamol increase the risk, although the number of ''regular'' users and the amount of these types of analgesic consumed were too small to confidently rule out a minor carcinogenic effect of phenacetin and paracetamol. (C) 1995 Wiley-Liss, Inc. C1 HUMBOLDT HOSP,BERLIN,GERMANY. NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. UNIV SYDNEY,WESTERN CLIN SCH,SYDNEY,NSW 2006,AUSTRALIA. UNIV UPPSALA HOSP,CANC EPIDEMIOL UNIT,S-75185 UPPSALA,SWEDEN. UNIV MINNESOTA,SCH PUBL HLTH,MINNEAPOLIS,MN 55455. DANISH CANC SOC,DANISH CANC REGISTRY,COPENHAGEN,DENMARK. GERMAN CANC RES CTR,DIV EPIDEMIOL,W-6900 HEIDELBERG,GERMANY. WESTAT CORP,ROCKVILLE,MD. RP MCCREDIE, M (reprint author), NSW CANC COUNCIL,CANC EPIDEMIOL RES UNIT,SYDNEY,NSW,AUSTRALIA. NR 25 TC 51 Z9 52 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 27 PY 1995 VL 60 IS 3 BP 345 EP 349 DI 10.1002/ijc.2910600312 PG 5 WC Oncology SC Oncology GA QG235 UT WOS:A1995QG23500011 PM 7829242 ER PT J AU MELLEMGAARD, A LINDBLAD, P SCHLEHOFER, B BERGSTROM, R MANDEL, JS MCCREDIE, M MCLAUGHLIN, JK NIWA, S ODAKA, N POMMER, W OLSEN, JH AF MELLEMGAARD, A LINDBLAD, P SCHLEHOFER, B BERGSTROM, R MANDEL, JS MCCREDIE, M MCLAUGHLIN, JK NIWA, S ODAKA, N POMMER, W OLSEN, JH TI INTERNATIONAL RENAL-CELL CANCER STUDY .3. ROLE OF WEIGHT, HEIGHT, PHYSICAL-ACTIVITY, AND USE OF AMPHETAMINES SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID RISK-FACTORS; CARCINOMA; POPULATION; OBESITY; WOMEN AB Although numerous studies have identified obesity or high relative weight as a risk factor for renal-cell cancer in women, the degree to which this effect is present in men remains unclear. A multicenter population-based case-control study concerning incident cases of histologically verified renal-cell cancer (n = 1,732) and age- and sex-matched controls (n = 2,309) was conducted in Australia, Denmark, Germany (2 centers), Sweden and the United States. Relative weight was estimated by the body mass index, and the association between this factor and other factors, such as height, physical activity and use of amphetamines, was measured by the relative risk estimated in logistic regression models. Body mass index was found to be a risk factor among women and, to a lesser extent, among men. A 3-fold increased risk (RR = 3.6, 95% CI = 2.3-5.7) was observed for women with a relative weight in the top 5% compared with those in the lowest quartile. Rate of weight change (estimated as weight change per annum in kilograms) appeared to be an independent risk factor among women but not among men. Physical activity and height were unrelated to risk of renal-cell cancer regardless of level of BMI, while use of amphetamines was associated with an increased risk among men, although no dose or duration effect was seen. Our findings verify the link between high relative weight and risk of renal-cell cancer, particularly among women. The mechanism that underlies this association is, however, still unclear, although the rate of weight change may play a role. (C) 1995 Wiley-Liss, Inc. C1 UNIV UPPSALA HOSP,CANC EPIDEMIOL UNIT,S-75185 UPPSALA,SWEDEN. SUNDSVALL HOSP,SUNDSVALL,SWEDEN. GERMAN CANC RES CTR,DIV CANC EPIDEMIOL,W-6900 HEIDELBERG,GERMANY. UPPSALA UNIV,DEPT STAT,UPPSALA,SWEDEN. UNIV MINNESOTA,SCH PUBL HLTH,DIV ENVIRONM HLTH,MINNEAPOLIS,MN 55455. NSW CANC COUNCIL,CANC EPIDEMIOL RES UNIT,SYDNEY,NSW,AUSTRALIA. NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,ROCKVILLE,MD. WESTAT CORP,ROCKVILLE,MD. HUMBOLT HOSP,BERLIN,GERMANY. RP MELLEMGAARD, A (reprint author), DANISH CANC SOC,DIV CANC EPIDEMIOL,BOX 839,STRANDBLVD 49,DK-2100 COPENHAGEN,DENMARK. NR 27 TC 89 Z9 91 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 27 PY 1995 VL 60 IS 3 BP 350 EP 354 PG 5 WC Oncology SC Oncology GA QG235 UT WOS:A1995QG23500012 PM 7829243 ER PT J AU HAYES, RB LIFF, JM POTTERN, LM GREENBERG, RS SCHOENBERG, JB SCHWARTZ, AG SWANSON, GM SILVERMAN, DT BROWN, LM HOOVER, RN FRAUMENI, JF AF HAYES, RB LIFF, JM POTTERN, LM GREENBERG, RS SCHOENBERG, JB SCHWARTZ, AG SWANSON, GM SILVERMAN, DT BROWN, LM HOOVER, RN FRAUMENI, JF TI PROSTATE-CANCER RISK IN US BLACKS AND WHITES WITH A FAMILY HISTORY OF CANCER SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID BREAST-CANCER; RELATIVES; OVARIAN AB Prostate cancer occurs move frequently in U.S. blacks than whites. A population-based case-control study which investigated the association with family history of cancer was carried out among 981 men (479 black, 502 white) with pathologically confirmed prostate cancer, diagnosed between August 1, 1986, and April 30, 1989, and 1,315 controls (594 black, 721 white). Study subjects, aged 40-79, resided in Atlanta, Detroit, and 10 counties in New Jersey, geographic areas covered by population-based cancer registries. Prostate cancer risk was significantly elevated among those who reported a history of prostate cancer in first-degree relatives (O.R. = 3.2; 95% C.I.: 2.0-5.0), with blacks and whites having similarly elevated risks. These risks were unchanged by statistical adjustment for job-related socio-economic status, education, income, and marital status. Overall, the ORs associated with history of prostate cancer in fathers and brothers were 2.5 (95% C.I.: 1.5-4.2) and 5.3 (95% C.I.: 2.3-12.5), respectively. Risks associated with a family history of prostate cancer were consistently elevated among younger and older subjects. Only small non-significant excesses of prostate cancer risk were associated with a family history of breast, colorectal, or other cancers. While familiar occurrence is a key risk factor for prostate cancer and likely to be genetically based, the similar familial risks among blacks and whites suggest that the ethnic disparity in incidence is influenced by environmental factors. (C) 1995 Wiley-Liss, Inc. C1 EMORY UNIV,SCH PUBL HLTH,DIV EPIDEMIOL,ATLANTA,GA 30329. NEW JERSEY STATE DEPT HLTH,SPECIAL EPIDEMIOL PROGRAM,TRENTON,NJ 08625. UNIV PITTSBURGH,SCH MED & FAMILY MED,DEPT CLIN EPIDEMIOL,PITTSBURGH,PA 15261. MICHIGAN STATE UNIV,COLL HUMAN MED,E LANSING,MI 48824. RP HAYES, RB (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EPIDEMIOL & BIOSTAT PROGRAM,EPN 418,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CP-51089, N01-CN-05225, N01-CP-51090] NR 29 TC 109 Z9 112 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 27 PY 1995 VL 60 IS 3 BP 361 EP 364 DI 10.1002/ijc.2910600315 PG 4 WC Oncology SC Oncology GA QG235 UT WOS:A1995QG23500014 PM 7829245 ER PT J AU DILLNER, J WIKLUND, F LENNER, P EKLUND, C FREDRIKSSONSHANAZARIAN, V SCHILLER, JT HIBMA, M HALLMANS, G STENDAHL, U AF DILLNER, J WIKLUND, F LENNER, P EKLUND, C FREDRIKSSONSHANAZARIAN, V SCHILLER, JT HIBMA, M HALLMANS, G STENDAHL, U TI ANTIBODIES AGAINST LINEAR AND CONFORMATIONAL EPITOPES OF HUMAN PAPILLOMAVIRUS TYPE-16 THAT INDEPENDENTLY ASSOCIATE WITH INCIDENT CERVICAL-CANCER SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID OPEN READING FRAME; SERUM ANTIBODIES; CAPSID PROTEINS; INFECTION; NEOPLASIA; L1 AB In a seroepidemiological study of incident cervical cancer, 94 cases and 188 population-based controls were used to evaluate the disease-association of IgG and IgA antibody responses against 6 human papillomavirus (HPV) type- 16 antigens. Nine of the tested antibody responses were positively associated with cervical cancer, with odds ratios (ORs) ranging from 2.5 to 15.0. The antibody responses mast strongly associated with cervical cancer were IgA against E6:10, an epitope derived from the carboxyterminal part of the HPVI6 Eb [OR = 15.0, confidence intervals (CI) = 5.9-48.6], IgG against HPVI6 virus-like particles (OR = 9.5, CI = 3.9-28.0) and IgG against the EI:19 epitope in the middle part of the El protein of HPV16 (OR = 7.7, CI = 3.9-16.5). When the 3 serological assays that showed the strongest association with cervical cancer were combined, positivity for 2 assays was found among 52% of cases at an OR of 29.9. We conclude that antibody responses to several linear and conformational HPV epitopes are independently associated with cervical cancer and that combined analysis of several HPV antibody responses can result in better predictive values for HPV-associated cancer. (C) 1995 Wiley-Liss, Inc. C1 KAROLINSKA INST,CTR MICROBIOL & TUMOR BIOL,S-17177 STOCKHOLM,SWEDEN. UMEA UNIV,DEPT ONCOL,UMEA,SWEDEN. UMEA UNIV,DEPT NUTR RES,UMEA,SWEDEN. UMEA UNIV,DEPT PATHOL,S-90187 UMEA,SWEDEN. UMEA UNIV,DEPT GYNECOL ONCOL,UMEA,SWEDEN. NIH,CELLULAR ONCOL LAB,BETHESDA,MD 20892. IMPERIAL CANC RES FUND,DEPT PATHOL,CAMBRIDGE,ENGLAND. NR 26 TC 64 Z9 66 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 27 PY 1995 VL 60 IS 3 BP 377 EP 382 PG 6 WC Oncology SC Oncology GA QG235 UT WOS:A1995QG23500017 PM 7530234 ER PT J AU TOZEREN, A KLEINMAN, HK GRANT, DS MORALES, D MERCURIO, AM BYERS, SW AF TOZEREN, A KLEINMAN, HK GRANT, DS MORALES, D MERCURIO, AM BYERS, SW TI E-SELECTIN-MEDIATED DYNAMIC INTERACTIONS OF BREAST-CANCER AND COLON-CANCER CELLS WITH ENDOTHELIAL-CELL MONOLAYERS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID TUMOR-CELLS; VASCULAR ENDOTHELIUM; CARCINOMA CELLS; ADHESION; EXPRESSION; RECEPTOR; LINES; INVITRO; VENULES AB The molecular mechanisms involved in the dynamic interaction of human breast carcinoma cells with the endothelial cell lining of lymphatic vessels and post-capillary blood venules are largely unknown. In the present study, laminar flow assays were used to investigate the ability of various normal breast cells and of breast- and colon-tumor cells to adhere to human umbilical cord endothelial cell monolayers. MCF-10A breast, MCF-7 and T-47D breast-carcinoma and clone A, RKO, and HT-29 colon-carcinoma cells accumulated and rolled, in the presence of now, on tumor necrosis factor (TNF)-stimulated but not on unstimulated endothelial cell monolayers. Non-tumor and tumor cells continued to form transient adhesions with TNF-stimulated endothelial cells even when the flow rate was increased to levels found in arteries. Incubation of TNF-stimulated endothelial cells with an E-selectin-specific monoclonal antibody (MAb) partially or completely inhibited dynamic interactions and diminished adhesion strength, whereas integrin beta(1)- and integrin alpha(6)-specific MAbs had no effect. A set of highly invasive breast-carcinoma cells (MDA-231, BT-549, HS-578t) neither adhered to nor rolled on resting or TNF-stimulated endothelial cell monolayers. However, after 5 min of static incubation, a fraction of these cells attached strongly to resting and TNF-stimulated endothelial cells and this static adhesion could not be blocked by an E-selectin-specific monoclonal antibody. Our results suggest that E-selectin is a major homing receptor in the metastasis of some breast and colon cancers. (C) 1995 Wiley-Liss, Inc. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. HARVARD UNIV,DEACONESS HOSP,SCH MED,CANC BIOL LAB,BOSTON,MA. GEORGETOWN UNIV,DEPT CELL BIOL,WASHINGTON,DC. GEORGETOWN UNIV,LOMBARDI CANC RES CTR,WASHINGTON,DC. RP TOZEREN, A (reprint author), CATHOLIC UNIV AMER,BIOMED ENGN PROGRAM,620 MICHIGAN AVE,WASHINGTON,DC 20064, USA. NR 26 TC 102 Z9 105 U1 1 U2 11 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 27 PY 1995 VL 60 IS 3 BP 426 EP 431 PG 6 WC Oncology SC Oncology GA QG235 UT WOS:A1995QG23500025 PM 7530236 ER PT J AU YE, WL ALI, N BEMBENEK, ME SHEARS, SB LAFER, EM AF YE, WL ALI, N BEMBENEK, ME SHEARS, SB LAFER, EM TI INHIBITION OF CLATHRIN ASSEMBLY BY HIGH-AFFINITY BINDING OF SPECIFIC INOSITOL POLYPHOSPHATES TO THE SYNAPSE-SPECIFIC CLATHRIN ASSEMBLY PROTEIN AP-3 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COATED VESICLES; MONOCLONAL-ANTIBODIES; F1-20 PROTEIN; BOVINE BRAIN; HEXAKISPHOSPHATE; CELLS; PHOSPHATES; NP185; PENTAKISPHOSPHATE; EXPRESSION AB Bacterially expressed synapse-specific clathrin assembly protein, AP-3 (F1-20/AP180/NP185/pp155), bound with high affinity both inositol hexakisphosphate (InsP(6)) (K-d = 239 nM) and diphosphoinositol pentakisphosphate (PP-InsP(5)) (K-d = 22 nM). The specificity of this ligand binding was demonstrated by competitive displacement of bound [H-3]InsP(6). IC50 values were as follows: PP-InsP(5) = 50 nM, InsP(6) = 240 nM, inositol-1,2,4,5,6-pentakisphosphate (Ins(1,2,4,5,6)P-5) = 2.2 mu M, inositol-1,3,4,5,6-pentakisphosphate (Ins(1,3,4,5,6)P-5) = 5 mu M, inositol-1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P-4) > 10 mu M, inositol-1,4,5-trisphosphate (Ins(1,4,5)P-3) > 10 mu M. Moreover, 10 mu M inositol hexasulfate (InsS(6)) displaced only 15% of [H-3]InsP(6). The physiological significance of this binding is the ligand-specific inhibition of clathrin assembly (PP-InsP(5) > InsP(6) > Ins(1,2,4,5,6)P-5); Ins(1,3,4,5,6)P-5 and InsS(6) did not inhibit clathrin assembly. We also observed high affinity binding of InsP(6) to purified bovine brain AP-3. We separately expressed the 33-kDa amino terminus and the 58-kDa carboxyl terminus, and it was the former that contained the high affinity inositol polyphosphate binding site, These studies suggest that specific inositol polyphosphates may play a role in the regulation of synaptic function by interacting with the synapse-specific clathrin assembly protein AP-3. C1 UNIV TEXAS,HLTH SCI CTR,INST BIOTECHNOL,CTR MOLEC MED,SAN ANTONIO,TX 78245. UNIV PITTSBURGH,DEPT BIOL SCI,PITTSBURGH,PA 15260. NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709. DUPONT CO INC,DEPT MED PROD,NEW ENGLAND NUCL,BOSTON,MA 02118. FU NINDS NIH HHS [R01 NS029051, NS29051] NR 37 TC 152 Z9 152 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 27 PY 1995 VL 270 IS 4 BP 1564 EP 1568 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QD204 UT WOS:A1995QD20400015 PM 7829485 ER PT J AU CAMPOS, KL GIOVANELLI, J KAUFMAN, S AF CAMPOS, KL GIOVANELLI, J KAUFMAN, S TI CHARACTERISTICS OF THE NITRIC-OXIDE SYNTHASE-CATALYZED CONVERSION OF ARGININE TO N-HYDROXYARGININE, THE FIRST OXYGENATION STEP IN THE ENZYMATIC-SYNTHESIS OF NITRIC-OXIDE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HYDROXY-L-ARGININE; BRAIN; HEME; INTERMEDIATE; OXIDATION; REDUCTION; CYTOCHROME-P-450; BIOSYNTHESIS; HEMOPROTEIN; COFACTOR AB The nitric oxide synthase-catalyzed conversion of L-arginine to L-citrulline and nitric oxide is known to be the sum of two partial reactions: oxygenation of arginine to N-hydroxyarginine, followed by oxygenation of N-hydroxyarginine to citrulline and nitric oxide, Whereas the conversion of N-hydroxyarginine to citrulline and nitric oxide has been the subject of a number of studies, the oxygenation of arginine to N-hydroxyarginine has received little attention, Here we show that substrate amounts of rat cerebellar nitric oxide synthase, in the absence of added NADPH, catalyze the conversion of arginine to N-hydroxyarginine as the dominant product, The product appears not to be tightly bound to the enzyme. A maximum of 0.16 mol of N-hydroxyarginine/mol of nitric oxide synthase subunit was formed. The reaction requires oxygen and the addition of Ca2+/calmodulin and is stimulated 3-fold by tetrahydrobiopterin. Upon addition of NADPH, citrulline is formed exclusively, Conversion of N-hydroxyarginine to citrulline, like the first partial reaction, requires Ca2+/calmodulin and is stimulated by tetrahydrobiopterin but differs from the first partial reaction in being completely dependent upon addition of NADPH, These results indicate that brain nitric oxide synthase contains an endogenous reductant that can support oxygenation of arginine but not of N-hydroxyarginine, The reductant is not NADPH, since the amount of nitric oxide synthase-bound NADPH is appreciably less than the amount required for N-hydroxyarginine synthesis. Possible candidates for this role are discussed in relation to proposed mechanisms of action of nitric oxide synthase. C1 NIMH, NEUROCHEM LAB, BETHESDA, MD 20895 USA. NR 36 TC 37 Z9 37 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 27 PY 1995 VL 270 IS 4 BP 1721 EP 1728 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QD204 UT WOS:A1995QD20400039 PM 7530247 ER PT J AU GOLDSMITH, ME GUDAS, JM SCHNEIDER, E COWAN, KH AF GOLDSMITH, ME GUDAS, JM SCHNEIDER, E COWAN, KH TI WILD-TYPE P53 STIMULATES EXPRESSION FROM THE HUMAN MULTIDRUG-RESISTANCE PROMOTER IN A P53-NEGATIVE CELL-LINE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TATA-BINDING PROTEIN; P-GLYCOPROTEIN GENE; RNA POLYMERASE-II; HUMAN MDR1 GENE; DNA-BINDING; LUNG-CANCER; HEAT-SHOCK; MUTANT P53; TRANSCRIPTION; SEQUENCE AB The effect of human wild type and mutant p53 proteins on the human multidrug resistance (MDR1) promoter was studied in a p53-negative human cell line. Transient expression of MDR1 promoter-chloramphenicol acetyltransferase reporter gene constructs (MDRCAT) cotransfected with p53 expression vectors was analyzed in H358 lung carcinoma cells. Cotransfection with a wild type p53 expression vector stimulated MDRCAT activity, while cotransfection with mutant p53 expression vectors altered at amino acid positions 181, 252, 258, or 273 failed to stimulate expression, Wild type p53 stimulation of MDRCAT activity was time dependent with maximal expression occurring 24-30 h following transfection and correlating with high p53 protein levels, MDR1 promoter deletion analysis suggested that the sequences involved in wild type p53 stimulation of MDRCAT activity were contained within the region from -39 to +53 relative to the start of transcription at +1. This region contains no TATA or p53 consensus binding sequence but does contain an initiator sequence. Wild type p53 stimulation of MDRCAT expression also occurred in parental and doxorubicin-resistant SW620 colon and parental 2780 ovarian cancer cell lines, indicating that wild type p53-mediated simulation of the MDR1 promoter is not restricted to a single cell line. RP GOLDSMITH, ME (reprint author), NCI,MED BRANCH,BLDG 10,RM 12N226,BETHESDA,MD 20892, USA. NR 59 TC 57 Z9 59 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 27 PY 1995 VL 270 IS 4 BP 1894 EP 1898 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QD204 UT WOS:A1995QD20400062 PM 7829527 ER PT J AU HU, Q DAVIDSON, D SCHWARTZBERG, PL MACCHIARINI, F LENARDO, MJ BLUESTONE, JA MATIS, LA AF HU, Q DAVIDSON, D SCHWARTZBERG, PL MACCHIARINI, F LENARDO, MJ BLUESTONE, JA MATIS, LA TI IDENTIFICATION OF RLK, A NOVEL PROTEIN-TYROSINE KINASE WITH PREDOMINANT EXPRESSION IN THE T-CELL LINEAGE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID X-LINKED AGAMMAGLOBULINEMIA; MICE LACKING; GENE; RECEPTOR; DOMAINS; PHOSPHORYLATION; INTERLEUKIN-2; DEFICIENCY; P56LCK; FAMILY AB The control of phosphorylation by protein tyrosine kinases represents an important regulatory mechanism in T cell growth, function, and differentiation. We have identified a 62-kDa murine protein tyrosine kinase predominantly expressed within the T cell lineage, which we have termed Rlk (for Resting lymphocyte kinase), rlk mRNA was found to be expressed in the fetal thymus as early as day 13 of embryonic development as well as in adult thymus and mature resting peripheral T cells, The sequence of rlk showed that it is most closely related to the subfamily of cytoplasmic tyrosine kinases that includes the Btk, Itk, and Tec proteins. However, Rlk differs from these kinases by virtue of its unique aminoterminal domain, which lacks a region of pleckstrin homology common to the other members of this protein subfamily. Examination of rlk abundance within different T cell subpopulations revealed preferential expression in Th1 relative to Th2 T cell clones, suggesting a possible role in signal transduction pathways that selectively regulate cytokine production in mature CD4(+) T cell subsets. Rlk thus represents a novel cytoplasmic tyrosine kinase with potential functions in intrathymic T cell development and mature T cell signaling. C1 ALEX PHARMACEUT,IMMUNOBIOL PROGRAM,NEW HAVEN,CT 06511. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. UNIV CHICAGO,DEPT ENDOCRINOL,CHICAGO,IL 60637. UNIV CHICAGO,DEPT PATHOL,CHICAGO,IL 60637. NIAID,IMMUNOL LAB,BETHESDA,MD 20098. PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RI Messier, Claude/A-2322-2008 OI Messier, Claude/0000-0002-4791-1763 FU NIDDK NIH HHS [DK07011] NR 44 TC 72 Z9 76 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 27 PY 1995 VL 270 IS 4 BP 1928 EP 1934 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QD204 UT WOS:A1995QD20400067 PM 7829530 ER PT J AU MARLEY, RJ SHIMOSATO, K GEWISS, M THORNDIKE, E GOLDBERG, SR SCHINDLER, CW AF MARLEY, RJ SHIMOSATO, K GEWISS, M THORNDIKE, E GOLDBERG, SR SCHINDLER, CW TI LONG-TERM SENSITIZATION TO THE BEHAVIORAL-EFFECTS OF NALTREXONE IS ASSOCIATED WITH REGIONALLY SPECIFIC CHANGES IN THE NUMBER OF MU-OPIOID AND DELTA-OPIOID RECEPTORS IN RAT-BRAIN SO LIFE SCIENCES LA English DT Article DE NALTREXONE; OPIOID RECEPTOR; MU RECEPTOR; DELTA RECEPTOR; SALIVATION; ENHANCED SENSITIVITY ID ENHANCED SENSITIVITY; UP-REGULATION; SUPERSENSITIVITY; BINDING AB Enhanced sensitivity to some of the behavioral effects of the opioid antagonist naltrexone (NTX) develops following once-weekly injections of cumulative doses of the drug. Rats treated with this regimen of NTX injections show enhanced sensitivity to the operant response rate decreasing effects of NTX and NTX-induced salivation. The enhanced sensitivity is long-lasting and appears to be produced through conditioning processes. We have conducted saturation binding assays to assess possible changes in the number and affinity of mu and delta opioid receptors in cortical, midbrain and hindbrain membrane preparations from Long-Evans rats treated once weekly for 8 weeks with cumulative doses of the drug (1, 3, 10, 30 and 100 mg/kg). H-3-DAMGO (0.5-21 nM) and H-3-pCl-DPDPE (0.04-4 nM) were used to characterize mu and delta receptors, respectively. NTX treatment had no effect on H-3-DAMGO binding in cortex, but decreased binding in midbrain and increased binding in hindbrain relative to saline-treated controls. Saturation analyses revealed that these differences reflected changes in the number, but not the affinity of mu receptors. NTX treatment also increased the amount of H-3-pCl-DPDPE bound to delta receptors in midbrain and hindbrain, but not in cortex. Again, these changes were due to changes in the number of receptors. Thus, chronic NTX differentially affects the number of mu and delta opioid receptors in various brain regions. C1 NIDA,DIV INTRAMURAL RES,BEHAV PHARMACOL & GENET SECT,PRECLIN PHARMACOL LAB,BALTIMORE,MD 21224. NIDA,DIV INTRAMURAL RES,GENET SECT,MOLEC NEUROBIOL BRANCH,BALTIMORE,MD 21224. KAWASAKI MED UNIV,DEPT PHARMACOL,KURASHIKI,OKAYAMA 70101,JAPAN. NR 16 TC 12 Z9 12 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JAN 27 PY 1995 VL 56 IS 10 BP 767 EP 774 DI 10.1016/0024-3205(95)00007-S PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA QD543 UT WOS:A1995QD54300007 PM 7885192 ER PT J AU MADRENAS, J WANGE, RL WANG, JL ISAKOV, N SAMELSON, LE GERMAIN, RN AF MADRENAS, J WANGE, RL WANG, JL ISAKOV, N SAMELSON, LE GERMAIN, RN TI ZETA-PHOSPHORYLATION WITHOUT ZAP-70 ACTIVATION-INDUCED BY TCR ANTAGONISTS OR PARTIAL AGONISTS SO SCIENCE LA English DT Article ID T-CELL-RECEPTOR; ANTIGEN-PRESENTING CELLS; TYROSINE PHOSPHORYLATION; CYTOCHROME-C; COMPLEX; CHAIN; LIGAND; COMPONENTS; ANALOG; KINASE AB Small changes in the peptide-major histocompatibility complex (MHC) molecule ligands recognized by antigen-specific T cell receptors (TCRs) can convert fully activating complexes into partially activating or even inhibitory ones, This study examined early TCR-dependent signals induced by such partial agonists or antagonists, In contrast to typical agonist ligands, both an antagonist and several partial agonists stimulated a distinct pattern of zeta chain phosphorylation and failed to activate associated ZAP-70 kinase, These results identify a specific step in the early tyrosine phosphorylation cascade that is altered after TCR engagement with modified peptide-MHC molecule complexes, This finding may explain the different biological responses to TCR occupancy by these variant ligands. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. RP MADRENAS, J (reprint author), NIAID,IMMUNOL LAB,LYMPHOCYTE BIOL SECT,BLDG 10,BETHESDA,MD 20892, USA. NR 49 TC 485 Z9 488 U1 0 U2 3 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JAN 27 PY 1995 VL 267 IS 5197 BP 515 EP 518 DI 10.1126/science.7824949 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QD403 UT WOS:A1995QD40300039 PM 7824949 ER PT J AU LIU, KJ JIANG, JJ SHI, XL GABRYS, H WALCZAK, T SWARTZ, HM AF LIU, KJ JIANG, JJ SHI, XL GABRYS, H WALCZAK, T SWARTZ, HM TI LOW-FREQUENCY EPR STUDY OF CHROMIUM(V) FORMATION FROM CHROMIUM(VI) IN LIVING PLANTS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ONE-ELECTRON REDUCTION; GLUTATHIONE-REDUCTASE; METAL CARCINOGENESIS; CHROMATE; CR(V) AB The reduction of Cr(VI) by green algae and higher plants was investigated using a low-frequency EPR spectrometer equipped with an extended loop gap resonator. Incubation of algae (Spirogyra and Mougeotia) with Cr(VI) generated both Cr(V) and Cr(III). The maximum Cr(V) signal was observed in about 10 minutes. Incubation of Cr(VI) with oat, soybean, and garlic generated Cr(V). The maximum Cr(V) peak appeared after more than 10 hours of incubation, and Cr(V) was located predominantly in the roots. The Cr(V) peak exhibited hyperfine splittings of about 0.79 gauss, typical of the Cr(V) complexes with diol-containing molecules. The results suggest that the reduction of Cr(VI) to lower oxidation states by living plants may provide a detoxification pathway for Cr(VI) in ecological systems. The results also indicate that low-frequency EPR may be used to investigate the metabolism of paramagnetic metal ions in intact plants. (C) 1995 Academic Press, Inc. C1 NCI,EXPTL PATHOL LAB,BETHESDA,MD 20892. JAGIELLONIAN UNIV,INST MOLEC BIOL,KRAKOW,POLAND. DARTMOUTH COLL,SCH MED,DEPT RADIOL,HANOVER,NH 03755. RI Shi, Xianglin/B-8588-2012 FU NCRR NIH HHS [RR-0811]; NIGMS NIH HHS [GM 34250] NR 21 TC 42 Z9 44 U1 1 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 26 PY 1995 VL 206 IS 3 BP 829 EP 834 DI 10.1006/bbrc.1995.1118 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QD255 UT WOS:A1995QD25500004 PM 7832793 ER PT J AU PANTALEO, G MENZO, S VACCAREZZA, M GRAZIOSI, C COHEN, OJ DEMAREST, JF MONTEFIORI, D ORENSTEIN, JM FOX, C SCHRAGER, LK MARGOLICK, JB BUCHBINDER, S GIORGI, JV FAUCI, AS AF PANTALEO, G MENZO, S VACCAREZZA, M GRAZIOSI, C COHEN, OJ DEMAREST, JF MONTEFIORI, D ORENSTEIN, JM FOX, C SCHRAGER, LK MARGOLICK, JB BUCHBINDER, S GIORGI, JV FAUCI, AS TI STUDIES IN SUBJECTS WITH LONG-TERM NONPROGRESSIVE HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID FOLLICULAR DENDRITIC CELLS; PRIMARY HIV-1 INFECTION; TYPE-1 INFECTION; LYMPH-NODES; AIDS; LYMPHADENOPATHY; LYMPHOCYTES; RESERVOIRS; VIREMIA; RNA AB Background. In a small percentage of persons infected with human immunodeficiency Virus type 1 (HIV-1), there is no progression of disease and CD4+ T-cell counts remain stable for many years. Studies of the histopathological, virologic, and immunologic characteristics of these persons may provide insight into the pathogenic mechanisms that lead to HIV disease and the protective mechanisms that prevent progression to overt disease. Methods and Results. We studied 15 subjects with long-term nonprogressive HIV infection and 18 subjects with progressive HIV disease. Nonprogressive infection was defined as seven or more years of documented HIV infection, with more than 600 CD4+ T cells per cubic millimeter, no antiretroviral therapy, and no HIV-related disease. Lymph nodes from the subjects with nonprogressive infection had significantly fewer of the hyperplastic features, and none of the involuted features, characteristic of nodes from subjects with progressive disease. Plasma levels of HIV-1 RNA and the viral burden in peripheral-blood mononuclear cells were both significantly lower in the subjects with nonprogressive infection than in those with progressive disease (P = 0.003 and P = 0.015, respectively). HIV could not be isolated from the plasma of the former, who also had significantly higher titers of neutralizing antibodies than the latter. There was viral replication, however, in the subjects with nonprogressive infection, and virus was consistently cultured from mononuclear cells from the lymph nodes. In the lymph nodes virus ''trapping'' varied with the degree of formation of germinal centers, and few cells expressing virus were found by in situ hybridization. HIV-specific cytotoxic activity was detected in ail seven subjects with nonprogressive infection who were tested. Conclusions. in persons who remain free of disease for many years despite HIV infection the Viral load is low, but viral replication persists. Lymph-node architecture and immune function appear to remain intact. C1 NIAID,DIV AIDS,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,SCH MED,DEPT MED CELLULAR IMMUNOL & CYTOMETRY,LOS ANGELES,CA. DUKE UNIV,MED CTR,CTR AIDS RES,DEPT SURG,DURHAM,NC. GEORGE WASHINGTON UNIV,DEPT PATHOL,WASHINGTON,DC. MOLEC HISTOL INC,GAITHERSBURG,MD. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT ENVIRONM HLTH SCI,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT IMMUNOL & INFECT DIS,BALTIMORE,MD. DEPT PUBL HLTH,AIDS OFF,RES BRANCH,SAN FRANCISCO,CA. UNIV ANCONA,SCH MED,INST MICROBIOL,ANCONA,ITALY. RP PANTALEO, G (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,RM 11B13,10 CTR DR,MSC 1876,BETHESDA,MD 20892, USA. RI Pantaleo, Giuseppe/K-6163-2016; OI Menzo, Stefano/0000-0002-4425-3750; VACCAREZZA, Mauro/0000-0003-3060-318X FU NIAID NIH HHS [U01-AI-35042, U01-AI-35039, U01-AI-35043] NR 35 TC 632 Z9 640 U1 1 U2 10 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 26 PY 1995 VL 332 IS 4 BP 209 EP 216 DI 10.1056/NEJM199501263320402 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA QC270 UT WOS:A1995QC27000002 PM 7808486 ER PT J AU SINHA, BK YAMAZAKI, H ELIOT, HM SCHNEIDER, E BORNER, MM OCONNOR, PM AF SINHA, BK YAMAZAKI, H ELIOT, HM SCHNEIDER, E BORNER, MM OCONNOR, PM TI RELATIONSHIPS BETWEEN PROTOONCOGENE EXPRESSION AND APOPTOSIS INDUCED BY ANTICANCER DRUGS IN HUMAN PROSTATE TUMOR-CELLS SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Article DE ONCOGENE; APOPTOSIS; CHEMORESISTANCE; PROSTATE TUMOR ID HUMAN MAMMARY; HUMAN-BREAST; GENE-EXPRESSION; OVARIAN-CANCER; RAS ONCOGENES; C-MYC; RESISTANCE; BCL-2; LINES; CIS-DIAMMINEDICHLOROPLATINUM(II) AB A variant of human prostate PC3 cells, isolated from PC3 cells, was shown to be significantly resistant (> 10-fold) to several clinically active anticancer drugs, including VP-16 and cisplatin. Previous studies showed that resistance to these drugs was not due to expression of the mdr1 gene, or modifications in topoisomerases but may have resulted from high expressions of certain proto-oncogenes (Yamazaki et al. (1994) Biochim. Biophys. Acta 1226, 89-96). Flow cytometry, DNA gel electrophoresis and northern blot analysis were used to further characterize drug responses in sensitive and resistant cells. Treatment of the sensitive PC3 cells with VP-16 and CDDP resulted in accumulation of cells in S and G2, and G1 and S phases, respectively, and caused significant degradation of the genomic DNA into internucleosomal sized DNA fragments, indicating apoptosis. In contrast, resistant PC3 cells showed little or no DNA fragmentation. Resistant PC3(R) cells expressed 2-3-fold more bcl2 protein than the parental PC3 cells, and overexpressed c-myc, c-jun and H-ras mRNA compared to sensitive cells. Treatment with VP-16 or CDDP significantly induced c-myc mRNA levels in sensitive PC3 cells. H-ras message was not affected by either VP-16 or CDDP treatment in PC3 cells. These studies, taken together, suggest that a differential susceptibility to apoptosis and chemosensitivity may be related to altered levels of bcl2 and/or oncogene overexpression in PC3(R) cells. C1 NCI,MED BRANCH,BETHESDA,MD 20892. NCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RP SINHA, BK (reprint author), NCI,CLIN PHARMACOL BRANCH,MOLEC & BIOCHEM PHARMACOL SECT,BLDG 10,ROOM 6N-119,BETHESDA,MD 20892, USA. RI Borner, Markus/B-7583-2011 NR 39 TC 55 Z9 57 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD JAN 25 PY 1995 VL 1270 IS 1 BP 12 EP 18 DI 10.1016/0925-4439(94)00065-X PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA QD643 UT WOS:A1995QD64300003 PM 7827130 ER PT J AU SKARLATOS, SI DUVERGER, N RADER, D KRUTH, HS AF SKARLATOS, SI DUVERGER, N RADER, D KRUTH, HS TI CHOLESTEROL EFFLUX FROM HUMAN MONOCYTE-DERIVED MACROPHAGES IN THE PRESENCE OF LPA-I-A-II SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Article DE HIGH DENSITY LIPOPROTEIN; MACROPHAGE; APOLIPOPROTEIN A-I; APOLIPOPROTEIN A-II; CHOLESTEROL EFFLUX ID HIGH-DENSITY-LIPOPROTEIN; HUMAN PLASMA; TRANSFER PROTEIN; TRANSGENIC MICE; ADIPOSE-CELLS; PARTICLES; ATHEROSCLEROSIS; SUBFRACTIONS; ELECTROPHORESIS; METABOLISM AB Previous epidemiological studies have suggested that the LpA-I subfraction of HDL is more protective than the LpA-I:A-II subfraction against the development of cardiovascular disease. A possible basis for a specific anti-atherogenic function of LpA-I emerged from studies of cholesterol efflux from cultured mouse adipocytes. LpA-I efficiently removed excess cholesterol from the mouse adipocytes, while LpA-I:A-II was ineffective. On the other hand, LpA-I:A-II was able to stimulate cholesterol efflux from a number of other cell types including rodent macrophages. Because of previously reported differences in HDL stimulation of cholesterol clearance from macrophages of different origins, we determined whether LpA-I:A-II could induce cholesterol efflux from cultured human monocyte-macrophages. Our findings showed that LpA-I:A-II and HDL(3) effectively stimulated cholesterol efflux from human monocyte-macrophages enriched with cholesterol by incubation with AcLDL. LpA-I:A-II also decreased by one-half the amount of cholesterol accumulated when macrophages were incubated with AcLDL and LpA-I:A-II together. Thus, it would appear that the differential anti-atherogenic effects of LpA-I:A-II and LpA-I do not derive from their effects on macrophage cholesterol efflux. Possibly these HDL subfractions differentially affect other biologic processes that modulate the development of cardiovascular disease. C1 NHLBI,EXPTL ATHEROSCLEROSIS SECT,BETHESDA,MD 20892. NHLBI,PEPTIDE CHEM SECT,BETHESDA,MD 20892. NR 48 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD JAN 25 PY 1995 VL 1270 IS 1 BP 19 EP 25 DI 10.1016/0925-4439(94)00067-Z PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA QD643 UT WOS:A1995QD64300004 PM 7827131 ER PT J AU RAUSCHECKER, JP AF RAUSCHECKER, JP TI DEVELOPMENTAL PLASTICITY AND MEMORY SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE VISUAL DEVELOPMENT; COMPENSATORY PLASTICITY; CEREBRAL CORTEX; HEBB SYNAPSE; ASSOCIATIVE MEMORY ID PRIMARY AUDITORY-CORTEX; EARLY VISUAL EXPERIENCE; SOMATOSENSORY CORTEX; SUPERIOR COLLICULUS; EARLY BLINDNESS; STRIATE CORTEX; HEBB SYNAPSES; CAT; AREA; REORGANIZATION AB The cerebral cortex of young kittens is known to be highly malleable during early postnatal development. However, most studies of developmental plasticity have been conducted in primary visual cortex. It has long been unclear to what extent similar plasticity exists in higher cortical areas. We have now studied developmental plasticity in the anterior ectosylvian (AE) region of the cat's parietal association cortex, which receives input from different sensory modalities. One area in this cortical region, which is predominantly visual in normal cats, area AEV, is taken over almost completely by auditory and somatosensory inputs, when cats are binocularly deprived of vision from birth. Furthermore, when single auditory neurons are tested with sound sources in free-field at different locations, they show sharper spatial tuning in visually deprived cats. This compensatory, crossmodal plasticity was explored at the behavioral level by testing visually deprived cats in an auditory localization task, and these cats could indeed localize sound sources more precisely than normal cats. These findings are interpreted as a form of adaptation of the young brain to an altered environment. Similar adaptation is still possible in adult brains by virtue of associative learning and long-term memory. It is argued that the synaptic mechanisms by which associative memories are stored in the cerebral cortex are similar to those in developmental plasticity, only the increment of learning is smaller in adult animals. RP RAUSCHECKER, JP (reprint author), NIMH,NEUROPHYSIOL LAB,POB 608,POOLESVILLE,MD 20837, USA. RI Rauschecker, Josef/A-4120-2013 NR 46 TC 43 Z9 44 U1 0 U2 1 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 JAN 23 PY 1995 VL 66 IS 1-2 BP 7 EP 12 DI 10.1016/0166-4328(94)00117-X PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA QH596 UT WOS:A1995QH59600003 PM 7755902 ER PT J AU ALKON, DL AF ALKON, DL TI MOLECULAR MECHANISMS OF ASSOCIATIVE MEMORY AND THEIR CLINICAL IMPLICATIONS SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE NETWORK ARCHITECTURE; ASSOCIATIVE LEARNING; MEMORY; ALZHEIMERS DISEASE; NEURAL NETWORK ID PROTEIN-KINASE-C; CURRENTS; HERMISSENDA; ACTIVATION AB In order to study how the human brain acquires, records, and recalls the relationships that comprise the images of human memory, our laboratory initiated a research strategy more than two decades ago. The strategy began with the hypothesis that the complex patterns of human memory are constructed from numerous simple relationships that are distributed over sensory space in our experience. This hypothesis further proposed that repeatable fundamental network architectures are distributed over brain structures to create internal images of our external and internal sensory experience. Based on this hypothesis, the first element of our research strategy was to (1) identify fundamental network architectures that learn and remember simple associative relationships such as those of Pavlovian conditioned responses; (2) demonstrate that the network biophysical and biochemical mechanisms of associative learning and memory in fundamental network architectures are conserved across species as diverse as those of snails, rabbits, and other mammals; (3) demonstrate that conserved memory mechanisms are targets of pathologic involvement in a human disease characterized by memory loss such as early Alzheimer's disease; (4) and derive mathematical and logical descriptions of the functions of biological associative network architectures during learning and memory. These descriptions would then be used to design artificial neural networks that would be implemented within computer programs. Observations demonstrating the plausibility of this research strategy are presented and discussed. RP NIH, ADAPT SYST LAB, 9000 ROCKVILLE PIKE, BLDG 36, ROOM 4A21, BETHESDA, MD 20892 USA. NR 15 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 EI 1872-7549 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD JAN 23 PY 1995 VL 66 IS 1-2 BP 151 EP 160 DI 10.1016/0166-4328(94)00142-3 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA QH596 UT WOS:A1995QH59600022 PM 7538770 ER PT J AU HORWITZ, B MCINTOSH, AR HAXBY, JV GRADY, CL AF HORWITZ, B MCINTOSH, AR HAXBY, JV GRADY, CL TI NETWORK ANALYSIS OF BRAIN COGNITIVE FUNCTION USING METABOLIC AND BLOOD-FLOW DATA SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE BRAIN METABOLISM; BLOOD FLOW; IMAGING; COGNITIVE FUNCTION; VISUAL PROCESSING; EXTRASTRIATE CORTEX; POSITRON EMISSION TOMOGRAPHY ID HUMAN EXTRASTRIATE CORTEX; SPATIAL VISION; PET IMAGES; OBJECT; DISSOCIATION; PATHWAYS; LANGUAGE; GLUCOSE; MEMORY; SYSTEM AB Functional neuroimaging has become a powerful tool for investigating the neurobiological foundations of cognition. An overview is presented of the two major strategies by which such data are currently analyzed. One strategy compares the pattern of activity between two (or more) tasks, looking for those brain areas that show significant changes. The second investigates the functional relationships between regional activities in an attempt to determine the systems-level neural networks mediating the tasks. Object and spatial visual processing tasks are used to illustrate each of these strategies. RP HORWITZ, B (reprint author), NIA, NEUROSCI LAB, BLDG 10, RM 6C414, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. RI McIntosh, Anthony/G-4955-2011; OI McIntosh, Anthony/0000-0002-1784-5662 NR 34 TC 53 Z9 53 U1 0 U2 2 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 JAN 23 PY 1995 VL 66 IS 1-2 BP 187 EP 193 DI 10.1016/0166-4328(94)00139-7 PG 7 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA QH596 UT WOS:A1995QH59600026 PM 7755889 ER PT J AU HUH, C NAGLE, JW KOZAK, CA ABRAHAMSON, M KARLSSON, S AF HUH, C NAGLE, JW KOZAK, CA ABRAHAMSON, M KARLSSON, S TI STRUCTURAL ORGANIZATION, EXPRESSION AND CHROMOSOMAL MAPPING OF THE MOUSE CYSTATIN-C-ENCODING GENE (CST3) SO GENE LA English DT Article DE RECOMBINANT GENOMIC DNA; GENE MAPPING; EXON; INTRON; PROMOTER SEQUENCE; PROTEINASE INHIBITOR; MULTIGENE FAMILY ID CYSTEINE-PROTEINASE-INHIBITOR; SUPERFAMILY; MEMBERS; FAMILY; VIRUS AB Cystatin C (CstC) is a potent cysteine-proteinase inhibitor. The structure of the mouse CstC-encoding gene (Cst3) was examined by sequencing a 6.1-kb genomic DNA containing the entire gene, as well as 0.9 kb of 5' flanking and 1.7 kb of its 3' flanking region. The sequence revealed that the overall organization of the gene is very similar to those of the genes encoding human CstC and other type-2 Cst, with two introns at positions identical to those in the human gene. The promoter area does not contain typical TATA or CAAT boxes. Two copies of a Spl-binding motif, GGGCGG, are present in the 5' flanking region within 300 bp upstream from the initiation codon. A hexa-nucleotide, TGTTCT, which is a core sequence of the androgen-responsive element (ARE), is found in the promoter region. This region also contains a 21-nucleotide sequence, 5'-AGACTAGCAGCTGACTGAAGC, which contains two potential binding sites for the transcription factor, AP-1. The mouse Cst3 mRNA was detected in all of thirteen tissues examined by Northern blot analysis. Cst3 was mapped in the mouse to a position on distal chromosome 2. C1 NINCDS,NEUROGENET SECT,BETHESDA,MD 20892. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. UNIV LUND HOSP,DEPT CLIN CHEM,S-22185 LUND,SWEDEN. RP HUH, C (reprint author), NINCDS,DEV & METAB NEUROL BRANCH,MOLEC & MED GENET SECT,BLDG 10,ROOM 3D04,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 29 TC 36 Z9 37 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JAN 23 PY 1995 VL 152 IS 2 BP 221 EP 226 DI 10.1016/0378-1119(94)00728-B PG 6 WC Genetics & Heredity SC Genetics & Heredity GA QD654 UT WOS:A1995QD65400014 PM 7835704 ER PT J AU HIROSE, T OBRIEN, DA JETTEN, AM AF HIROSE, T OBRIEN, DA JETTEN, AM TI RTR - A NEW MEMBER OF THE NUCLEAR RECEPTOR SUPERFAMILY THAT IS HIGHLY EXPRESSED IN MURINE TESTIS SO GENE LA English DT Article DE ORPHAN RECEPTOR; RXR; SPERMATOGENESIS; TRANSCRIPTION FACTOR; SPERMATIDS; PCR ID ISOLATED SPERMATOGENIC CELLS; RETINOIC ACID; MOUSE; CLONING; IDENTIFICATION; TRANSCRIPTION; LOCALIZATION; SEQUENCES; FAMILY; GENES AB We have identified and cloned a novel member of the nuclear receptor superfamily from murine testis, referred to as retinoid receptor-related testis-associated receptor or RTR. Degenerate PCR primers homologous to two conserved regions of the DNA-binding domain of members of this superfamily were employed to identify this gene. The aminoacid sequence of RTR is most closely related to that of the mouse RXRs with an overall identity of 32-34; the highest similarity (61%) is observed in the DNA-binding domain. Northern blot analysis using RNA from multiple tissues showed that RTR is predominantly expressed in the testis. Northern blot analysis using RNA from different testicular cell types showed that RTR mRNA is not expressed in early germ cells or Sertoli cells but is most abundant in round spermatids, Our observations suggest that this putative transcription factor plays a role in the regulation of gene expression particularly during the post-meiotic phase of spermatogenesis. C1 NIEHS,PULM PATHOBIOL LAB,CELL BIOL SECT,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,REPROD BIOL LAB,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT PEDIAT,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT CELL BIOL & ANAT,CHAPEL HILL,NC 27599. RI Hirose, Takahisa /E-6117-2011; OI Jetten, Anton/0000-0003-0954-4445 FU NCI NIH HHS [CA16086]; NICHD NIH HHS [HD26485, P30-HD18968, R01 HD026485] NR 27 TC 70 Z9 73 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JAN 23 PY 1995 VL 152 IS 2 BP 247 EP 251 DI 10.1016/0378-1119(94)00656-D PG 5 WC Genetics & Heredity SC Genetics & Heredity GA QD654 UT WOS:A1995QD65400019 PM 7835709 ER PT J AU MILLS, JL MCPARTLIN, JM KIRKE, PN LEE, YJ CONLEY, MR WEIR, DG SCOTT, JM AF MILLS, JL MCPARTLIN, JM KIRKE, PN LEE, YJ CONLEY, MR WEIR, DG SCOTT, JM TI HOMOCYSTEINE METABOLISM IN PREGNANCIES COMPLICATED BY NEURAL-TUBE DEFECTS SO LANCET LA English DT Article ID VITAMIN SUPPLEMENTATION; PLASMA; PREVENTION; METHIONINE; FOLATE; SERUM; ACID AB Folic acid taken around the time of conception can prevent many neural-tube defects, Women with low-normal vitamin B-12 values may also be at increased risk. We considered whether homocysteine metabolism via the enzyme methionine synthase, which requires both folate and B-12, could be the critical defect in folate-related neural tube defects. Blood was obtained during pregnancies that produced 81 infants with neural-tube defects and 323 normal children, Samples were assayed for homocysteine, methylmalonic acid, plasma folate, red-cell folate, and B-12. Mothers of children with neural-tube defects had significantly higher homocysteine values (8.62 [SD 2.8] mu mol/L) than did B-12-matched controls (7.96 [2.5] mu mol/L, p=0.03). The difference was significant (p=0.004) in the lower half of the B-12 distribution after adjusting for plasma folate. Our study shows that an abnormality in homocysteine metabolism, apparently related to methionine synthase, is present in many women who give birth to children with neural-tube defects. Overcoming this abnormality is likely to be the mechanism by which folic acid prevents neural-tube defects. These findings suggest that the most effective periconceptional prophylaxis to prevent neural-tube defects may require B-12 as well as fotic acid. C1 HLTH RES BOARD,DUBLIN,IRELAND. UNIV DUBLIN TRINITY COLL,DEPT CLIN MED,DUBLIN,IRELAND. UNIV DUBLIN TRINITY COLL,DEPT BIOCHEM,DUBLIN,IRELAND. RP MILLS, JL (reprint author), NICHHD,DESPR,PEDIAT EPIDEMIOL SECT,EPIDEMIOL BRANCH,6100 EXECUT BLVD,ROOM 7B03,BETHESDA,MD 20892, USA. NR 13 TC 511 Z9 522 U1 1 U2 24 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0099-5355 J9 LANCET JI Lancet PD JAN 21 PY 1995 VL 345 IS 8943 BP 149 EP 151 DI 10.1016/S0140-6736(95)90165-5 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA QC550 UT WOS:A1995QC55000008 PM 7741859 ER PT J AU DARWISH, M FARIS, R CLEMENS, J RAO, M EDELMAN, R AF DARWISH, M FARIS, R CLEMENS, J RAO, M EDELMAN, R TI HEPATITIS-C VIRUS SO LANCET LA English DT Letter C1 AIN SHAMS UNIV,FAC MED,DEPT COMMUNITY & PREVENT MED,CAIRO,EGYPT. NICHHD,EPIDEMIOL BRANCH,BETHESDA,MD. UNIV MARYLAND,SCH MED,DEPT MED,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,CTR VACCINE DEV,BALTIMORE,MD 21201. RP DARWISH, M (reprint author), AIN SHAMS UNIV,FAC MED,DEPT MICROBIOL,CAIRO,EGYPT. NR 4 TC 2 Z9 2 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0099-5355 J9 LANCET JI Lancet PD JAN 21 PY 1995 VL 345 IS 8943 BP 190 EP 191 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QC550 UT WOS:A1995QC55000036 PM 7529861 ER PT J AU ANDERSSONELLSTROM, A DILLNER, J HAGMAR, B SCHILLER, J FORSSMAN, L AF ANDERSSONELLSTROM, A DILLNER, J HAGMAR, B SCHILLER, J FORSSMAN, L TI HPV-16 TRANSMISSION - REPLY SO LANCET LA English DT Letter C1 DIST HLTH CTR GRIPEN,S-65009 KARLSTAD,SWEDEN. KAROLINSKA INST,CTR MICROBIOL & TUMOR BIOL,STOCKHOLM,SWEDEN. OSLO UNIV HOSP,DEPT CLIN CYTOL,OSLO,NORWAY. NIH,CELLULAR ONCOL LAB,BETHESDA,MD. OSTRA HOSP,DEPT OBSTET & GYNAECOL,GOTHENBURG,SWEDEN. RP ANDERSSONELLSTROM, A (reprint author), CTR PUBL HLTH RES,S-65009 KARLSTAD,SWEDEN. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0099-5355 J9 LANCET JI Lancet PD JAN 21 PY 1995 VL 345 IS 8943 BP 197 EP 198 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QC550 UT WOS:A1995QC55000051 ER PT J AU KIPERSZTOK, S OSAWA, GA LIANG, LF MODI, WS DEAN, J AF KIPERSZTOK, S OSAWA, GA LIANG, LF MODI, WS DEAN, J TI POM-ZP3, A BIPARTITE TRANSCRIPT DERIVED FROM HUMAN ZP3 AND A POM121 HOMOLOG SO GENOMICS LA English DT Article ID MOUSE ZONA PELLUCIDA; OOCYTE-SPECIFIC EXPRESSION; SPERM RECEPTOR; DEVELOPMENTAL REGULATION; GENOMIC ORGANIZATION; PROTEIN; GENES; SEQUENCE; GLOBIN; ZP-2 AB Human POM-ZP3 is a novel bipartite RNA transcript that is derived from a gene homologous to rat POM121 (a nuclear pore membrane protein) and ZP3 (a sperm receptor ligand in the zona pellucida). The 5' region is 77% identical to the 5' end of the coding region of rat POM121 and appears to represent a partial duplication of a gene encoding a human homologue of this rodent gene. The 3' end of the POM-ZP3 transcript is 99% identical to ZP3 and appears to have arisen from a duplication of the last four exons (exons 5-8) of ZP3. Using Northern blots and RT-PCR, POM-ZP3 transcripts were detected in human ovaries, testes, spleen, thymus, lymphocytes, prostate, and intestines. The longest open reading frame encodes a conceptual protein of 210 amino acids, the first 76 of which are 83% identical to residues 241-315 of rat POM121. The next 125 amino acids are 98% identical to residues 239-363 of the 424-amino-acid human ZP3 protein. By fluorescence in situ hybridization, genomic fragments of ZP3 and a human homologue of POM121 were localized to chromosome 7q11.23. Taken together, these data suggest that partial duplications of human ZP3 and a POM121-like gene have resulted in a fusion transcript, POM-ZP3, that is expressed in multiple human tissues. (C) 1995 Academic Press, Inc. C1 NIDDK,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,DEPT OBSTET & GYNECOL,WASHINGTON,DC. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NR 24 TC 25 Z9 26 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JAN 20 PY 1995 VL 25 IS 2 BP 354 EP 359 DI 10.1016/0888-7543(95)80033-I PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA QH779 UT WOS:A1995QH77900002 PM 7789967 ER PT J AU AVRAHAM, KB FLETCHER, C OVERDIER, DG CLEVIDENCE, DE LAI, E COSTA, RH JENKINS, NA COPELAND, NG AF AVRAHAM, KB FLETCHER, C OVERDIER, DG CLEVIDENCE, DE LAI, E COSTA, RH JENKINS, NA COPELAND, NG TI MURINE CHROMOSOMAL LOCATION OF 8 MEMBERS OF THE HEPATOCYTE NUCLEAR FACTOR-3 FORK HEAD WINGED HELIX FAMILY OF TRANSCRIPTION FACTORS SO GENOMICS LA English DT Article ID GENETIC-LINKAGE MAP; MOUSE; LOCALIZATION; EXPRESSION; IDENTIFICATION; ORGANIZATION; BACKCROSS; CLONING; DOMAIN; GENOME AB A 100-amino-acid DNA-binding motif, known as the winged helix, was first identified in the mammalian hepatocyte nuclear factor-3 (HNF-3) and Drosophila fork head family of transcription factors. Subsequently, more than 40 different genes that contain the winged helix motif have been identified. In the studies described here, we have determined the murine chromosomal location of eight members of this gene family, HFH-1, HFH-3, HFH-4, HFH-5, HFH-6, HFH-8, BF-1, and BF-2, by interspecific backcross analysis. These genes, designated HNF-3 fork head homolog 1 (Hfh1), Hfh3, Hfh4, Hfh5, Hfh6, Hfh8, Hfh9, and Hfh10, respectively, mapped to 6 different mouse autosomes and are thus well dispersed throughout the mouse genome. Based on this mapping information, we predict the chromosomal location of these genes in humans and discuss the potential of these genes as candidates for uncloned mouse mutations. (C) 1995 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. UNIV ILLINOIS,COLL MED,DEPT BIOCHEM,CHICAGO,IL 60612. MEM SLOAN KETTERING CANC CTR,CELL BIOL & GENET PROGRAM,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,DIV ENDOCRINOL,NEW YORK,NY 10021. FU NCI NIH HHS [N01-CO-74101]; NIGMS NIH HHS [5F32GM15909-02] NR 37 TC 24 Z9 25 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JAN 20 PY 1995 VL 25 IS 2 BP 388 EP 393 DI 10.1016/0888-7543(95)80038-N PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA QH779 UT WOS:A1995QH77900007 PM 7789972 ER PT J AU JANKOWSKI, SA DEJONG, P MELTZER, PS AF JANKOWSKI, SA DEJONG, P MELTZER, PS TI GENOMIC STRUCTURE OF SAS, A MEMBER OF THE TRANSMEMBRANE-4 SUPERFAMILY AMPLIFIED IN HUMAN SARCOMAS SO GENOMICS LA English DT Article ID TUMOR-ASSOCIATED ANTIGEN; MOLECULAR-CLONING; CHROMOSOMAL LOCALIZATION; TRANSCRIPTION FACTOR; MONOCLONAL-ANTIBODY; CELL MOTILITY; GENE FAMILY; PROTEIN; CD53; IDENTIFICATION AB SAS is a recently identified member of the transmembrane 4 superfamily (TM4SF) that is frequently amplified in human sarcomas. To further its characterization and to confirm its classification, the genomic structure of the SAS gene was determined. The SAS gene covers approximately 3.2 kb of DNA, It contains six exons within its translated region, three of which are highly conserved in the TM4SF. 5' to the translation start site are two putative transcription start sites, two CCAAT consensus sequences, and potential binding sites for both Spl and ATF transcription factors. Comparison of SAS organization to human ME491, CD9, and CD53 and murine CD53 and TAPA-1 confirms that SAS is a member of this family of genes and is consistent with the theory that these genes arose through duplication and divergent evolution. (C) 1995 Academic Press, Inc. C1 NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892. UNIV MICHIGAN,DEPT HUMAN GENET,ANN ARBOR,MI 48109. ROSWELL PK CANC INST,BUFFALO,NY 14203. NR 45 TC 13 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JAN 20 PY 1995 VL 25 IS 2 BP 501 EP 506 DI 10.1016/0888-7543(95)80051-M PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA QH779 UT WOS:A1995QH77900020 PM 7789984 ER PT J AU HULSEBOS, TJM JENKINS, NA GILBERT, DJ COPELAND, NG AF HULSEBOS, TJM JENKINS, NA GILBERT, DJ COPELAND, NG TI THE BETA-CRYSTALLIN GENES ON HUMAN-CHROMOSOME-22 DEFINE A NEW REGION OF HOMOLOGY WITH MOUSE CHROMOSOME-5 SO GENOMICS LA English DT Note ID LINKAGE MAP; MARKERS; LOCALIZATION; MUTATION; DELETION; CATARACT AB The human beta crystallin genes CRYBB2, CRYBB2P1, CRYBB3, and CRYBA4 are located in 22q11.2. Using interspecific backcross analysis, we mapped the mouse homologues of CRYBB2, CRYBB3, and CRYBA4 (i.e., Crybb2, Crybb3, and Cryba4) to the central region of mouse chromosome 5. The homologue of human CRYBB2P1 is absent in mouse. These assignments define a new region of homology in human and mouse. (C) 1995 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RP HULSEBOS, TJM (reprint author), UNIV AMSTERDAM,ACAD MED CTR,INST HUMAN GENET,MEIBERGDREEF 15,1105 AZ AMSTERDAM,NETHERLANDS. FU NCI NIH HHS [N01-CO-74101] NR 19 TC 11 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JAN 20 PY 1995 VL 25 IS 2 BP 574 EP 576 DI 10.1016/0888-7543(95)80062-Q PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA QH779 UT WOS:A1995QH77900031 PM 7789995 ER PT J AU KEEN, TL INGLEHEARN, CF PATEL, RJ GREEN, ED PELUSO, DC BHATTACHARYA, SS AF KEEN, TL INGLEHEARN, CF PATEL, RJ GREEN, ED PELUSO, DC BHATTACHARYA, SS TI LOCALIZATION OF THE AQUAPORIN-1 (AQP1) GENE WITHIN A YAC CONTIG CONTAINING THE POLYMORPHIC MARKERS D7S632 AND D75526 SO GENOMICS LA English DT Note ID CHIP C1 NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP KEEN, TL (reprint author), INST OPHTHALMOL,DEPT MOLEC GENET,BATH ST,LONDON EC1V 9EL,ENGLAND. FU NHGRI NIH HHS [P50-HG00201]; Wellcome Trust NR 7 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JAN 20 PY 1995 VL 25 IS 2 BP 599 EP 600 DI 10.1016/0888-7543(95)80070-3 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA QH779 UT WOS:A1995QH77900039 PM 7540589 ER PT J AU AVRAHAM, KB LEVANON, D NEGREANU, V BERNSTEIN, Y GRONER, Y COPELAND, NG JENKINS, NA AF AVRAHAM, KB LEVANON, D NEGREANU, V BERNSTEIN, Y GRONER, Y COPELAND, NG JENKINS, NA TI MAPPING OF THE MOUSE HOMOLOG OF THE HUMAN RUNT DOMAIN GENE, AML2, TO THE DISTAL REGION OF MOUSE CHROMOSOME-4 SO GENOMICS LA English DT Note ID LINKAGE MAP; FAMILY C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. WEIZMANN INST SCI,DEPT MOLEC GENET & VIROL,IL-76100 REHOVOT,ISRAEL. FU NCI NIH HHS [N01-CO-74101]; NIGMS NIH HHS [5F32GM15909-02] NR 9 TC 16 Z9 16 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JAN 20 PY 1995 VL 25 IS 2 BP 603 EP 605 DI 10.1016/0888-7543(95)80073-U PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA QH779 UT WOS:A1995QH77900042 PM 7790005 ER PT J AU KOLLAR, R PETRAKOVA, E ASHWELL, G ROBBINS, PW CABIB, E AF KOLLAR, R PETRAKOVA, E ASHWELL, G ROBBINS, PW CABIB, E TI ARCHITECTURE OF THE YEAST-CELL WALL - THE LINKAGE BETWEEN CHITIN AND BETA(1-]3)-GLUCAN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; GLUCAN; PURIFICATION; ENZYME; OLIGOSACCHARIDES AB To isolate the putative linkage region between chitin and beta(1-->3)-glucan, Saccharomyces cerevisiae cell walls were digested with beta(1-->3)-endoglucanase and the reducing ends of the enzyme-resistant glucose chain stubs were labeled by reduction with borotritide, The radioactive material was further digested with exochitinase to remove the bulk of the chitin, and the Liberated oligosaccharides were fractionated on a sizing column, A single peak (compound I) was found to consist of N-acetylglucosamine, glucose, and glucitol residues in the ratio 1:2:1, By digestion with beta-N-acetylglucosaminidase and by NMR spectroscopy, N-acetylglucosamine was identified as the nonreducing terminus, linked to laminaritriitol by a beta(1-->4) bond, Five additional oligosaccharides were recovered, two being analogs of compound I, with 1 or 3 glucose units, respectively; the remaining three were shown to be the reduced analogs of laminaribiose, laminaritriose, and laminaritetraose. The presence of N-acetylglucosamine-containing oligosaccharides arises from the activity of chitinase in cleaving 2 sugar units sequentially in those chains containing an odd number of N-acetylglucosamine residues; correspondingly, oligosaccharides containing only glucose and sorbitol derive from even-numbered chitin chains, a result implying that chitinase can hydrolyze the linkage between N-acetylglucosamine and glucose. It is concluded that the terminal reducing residue of a chitin chain is attached to the nonreducing end of a beta(1-->3)-glucan chain by a beta(1-->4) linkage. Experiments with appropriate mutants showed that synthesis of the chitin combined with glucan is catalyzed by chitin synthetase 3. The timing and possible mechanism of formation of the chitin-glucan linkage is discussed. C1 NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892. NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. FU NIDDK NIH HHS [DK0016] NR 25 TC 191 Z9 194 U1 2 U2 11 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 20 PY 1995 VL 270 IS 3 BP 1170 EP 1178 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QB156 UT WOS:A1995QB15600031 PM 7836376 ER PT J AU BRADY, JP KANTOROW, M SAX, CM DONOVAN, DM PIATIGORSKY, J AF BRADY, JP KANTOROW, M SAX, CM DONOVAN, DM PIATIGORSKY, J TI MURINE TRANSCRIPTION FACTOR ALPHA-A-CRYSTALLIN BINDING-PROTEIN-I - COMPLETE SEQUENCE, GENE STRUCTURE, EXPRESSION, AND FUNCTIONAL INHIBITION VIA ANTISENSE RNA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; NF-KAPPA-B; ZINC-FINGER PROTEIN; MESSENGER-RNA; EUKARYOTIC CELLS; RAT TESTIS; MOUSE; ENHANCER; PROMOTER; DNA AB alpha A-crystallin binding protein I (alpha A-CRYBP1) is a ubiquitously expressed DNA binding protein that was previously identified by its ability to interact with a functionally important sequence in the mouse alpha A-crystallin gene promoter, Here, we have cloned a single copy gene with 10 exons spanning greater than 70 kb of genomic DNA that encodes alpha A-CRYBP1. The mouse alpha A-CRYBP1 gene specifies a 2,688-amino acid protein with 72% amino acid identity to its human homologue, PRDII-BF1. Both the human and the mouse proteins contain two sets of consensus C2H2 zinc fingers at each end as well a central nonconsensus zinc finger. The alpha A-CRYBP1 gene produces a 9.5-kb transcript in II different tissues as well as a testis-specific, 7.7 kb transcript, alpha A-CRYBP1 cDNA clones were isolated from adult mouse brain and testis as well as from cell lines derived from mouse lens (alpha TN4-1) and muscle (C2C12). A single clone isolated from the muscle C2C12 library contains an additional exon near the 5'-end that would prevent production of a functional protein if the normal translation start site were utilized; however, there is another potential initiation codon located downstream that is in frame with the rest of the coding region, In addition, we identified multiple cDNAs from the testis in which the final intron is still present. Finally, we used an antisense expression construct derived from an alpha A-CRYBP1 cDNA clone to provide the first functional evidence that alpha A-CRYBP1 regulates gene expression, When introduced into the alpha TN4-1 mouse lens cell line, the antisense construct significantly inhibited expression from a heterologous promoter that utilized the alpha A-CRYBP1 binding site as an enhancer. C1 NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892. NR 45 TC 27 Z9 28 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 20 PY 1995 VL 270 IS 3 BP 1221 EP 1229 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QB156 UT WOS:A1995QB15600038 PM 7836383 ER PT J AU KELLEY, CA OBERMAN, F YISRAELI, JK ADELSTEIN, RS AF KELLEY, CA OBERMAN, F YISRAELI, JK ADELSTEIN, RS TI A XENOPUS NONMUSCLE MYOSIN HEAVY-CHAIN ISOFORM IS PHOSPHORYLATED BY CYCLIN-P34(CDC2) KINASE DURING MEIOSIS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SMOOTH-MUSCLE MYOSIN; CONTROL GENE CDC2+; PROTEIN-KINASE; LIGHT CHAIN; CELL-CYCLE; M-PHASE; MESSENGER-RNAS; TYROSINE PHOSPHORYLATION; MAP KINASE; MITOSIS AB There are two vertebrate nonmuscle myosin heavy chain (MHC) genes that encode two separate isoforms of the heavy chain, MHC-A and MHC-B. Recent work has identified additional, alternatively spliced isoforms of MRC-R cDNA with inserted sequences of 30 nucleotides (chicken and human) or 48 nucleotides (Xenopus) at a site corresponding to the ATP binding region in the MHC protein (Takahashi, M., Kawamoto, S. and Adelstein, R. S. (1992) J. Biol. Chem. 267, 17864-17871) and Bhatia-Dey, N., Adelstein, R. S., and Dawid, I. B. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 2856-2859). The deduced amino acid sequence of these inserts contains a consensus sequence for phosphorylation by cyclin-p34(cdc2) (cdc2) kinase. In cultured Xenopus XTC cells, we have identified two inserted MHC-B isoforms and a noninserted MHC-A isoform by immunoblotting of cell extracts. When myosin was immunoprecipitated from XTC cells and phosphorylated in vitro with cdc2 kinase, the kinase catalyzed the phosphorylation of both inserted MRC-B isoforms but not MHC-A. Isoelectric focusing of tryptic peptides generated from MHC-B phosphorylated with cdc2 kinase revealed one major phosphopeptide that was purified by reverse phase high performance liquid chromatography and sequenced. The phosphorylated residue was Ser-214, the cdc2 kinase consensus site within the insert near the ATP binding region. The same site was phosphorylated in intact XTC cells during log phase of growth and in cell-free lysates of Xenopus eggs stabilized in second meiotic metaphase but not interphase. Moreover, Ser-214 phosphorylation was detected during maturation of Xenopus oocytes when the cdc2 kinase-containing maturation-promoting factor was activated, but not in G(2) interphase-arrested oocytes. These results demonstrate that MBC-B phosphorylation is tightly regulated by cdc2 kinase during meiotic cell cycles. Furthermore, MHC-A and MHC-B isoforms are differentially phosphorylated at these stages, suggesting that they may serve different functions in these cells. C1 HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT ANAT & EMBRYOL,IL-91010 JERUSALEM,ISRAEL. RP KELLEY, CA (reprint author), NHLBI,MOLEC CARDIOL LAB,BLDG 10,RM 8N-202,10 CTR DR MSC 1762,BETHESDA,MD 20892, USA. OI Adelstein, Robert/0000-0002-8683-2144 NR 58 TC 28 Z9 28 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 20 PY 1995 VL 270 IS 3 BP 1395 EP 1401 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QB156 UT WOS:A1995QB15600063 PM 7836406 ER PT J AU PETERSON, SR JESCH, SA CHAMBERLIN, TN DVIR, A RABINDRAN, SK WU, C DYNAN, WS AF PETERSON, SR JESCH, SA CHAMBERLIN, TN DVIR, A RABINDRAN, SK WU, C DYNAN, WS TI STIMULATION OF THE DNA-DEPENDENT PROTEIN-KINASE BY RNA-POLYMERASE-II TRANSCRIPTIONAL ACTIVATOR PROTEINS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TERMINAL TRANSACTIVATION DOMAIN; HEAT-SHOCK PROTEIN; GAL4 DERIVATIVES; GENE-TRANSCRIPTION; BINDING ACTIVITY; KU-AUTOANTIGEN; CELL EXTRACTS; PHOSPHORYLATION; TEMPLATE; INVITRO AB The DNA dependent protein kinase (DNA-PK) phosphorylates RNA polymerase II and a number of transcription factors. We now show that the activity of DNA-PK is directly stimulated by certain transcriptional activator proteins, including the human heat shock transcription factor 1 (HSF1) and a transcriptionally active N-terminal 147 amino acid GAL4 derivative. Stimulation of DNA-PK activity required specific sequences in the activator proteins outside the minimal DNA binding domains. The stimulation of DNA-PK activity also required DNA and was greater with DNA containing relevant activator binding sites. Comparison of different HSF binding fragments showed that optimal stimulation occurred when two HSF binding sites were present. Stimulation with HSF and GALE was synergistic with Ku protein, another regulator of DNA-PK activity. DNA-PK is tightly associated with the transcriptional template, and an increase in its activity could potentially influence transcription through the phosphorylation of proteins associated with the transcription complex. C1 UNIV COLORADO,DEPT CHEM & BIOCHEM,BOULDER,CO 80309. NCI,BIOCHEM LAB,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM 35866] NR 43 TC 58 Z9 59 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 20 PY 1995 VL 270 IS 3 BP 1449 EP 1454 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QB156 UT WOS:A1995QB15600071 PM 7836414 ER PT J AU CHAN, KC MUSCHIK, GM ISSAQ, HJ SIITERI, PK AF CHAN, KC MUSCHIK, GM ISSAQ, HJ SIITERI, PK TI SEPARATION OF ESTROGENS BY MICELLAR ELECTROKINETIC CHROMATOGRAPHY SO JOURNAL OF CHROMATOGRAPHY A LA English DT Note ID PERFORMANCE LIQUID-CHROMATOGRAPHY; CAPILLARY CHROMATOGRAPHY; BREAST-CANCER; ELECTROPHORESIS; ESTRIOL; CORTICOSTEROIDS; CELLS; SERUM; FLUID AB Capillary electrophoresis of the sex hormone estrogens using different buffer components was investigated. Free zone electrophoresis with 10 mM phosphate buffer (pH 11.5) or 10 mM phosphate buffer with 10-20% methanol was not effective in separating the ten estrogens used in this study. However, nine estrogens were resolved by micellar electrokinetic chromatography using a 10 mM berate buffer (pH 9.2) containing 100 mM sodium cholate. In addition, some estrogens were partially separated using sodium dodecyl sulfate (SDS) micellar buffers; however, the addition of modifiers such as organic solvents or cyclodextrins improved resolutions significantly. Using a 10 mM phosphate buffer (pH 7.0) containing 50 mM SDS and 20% methanol, or a 10 mM berate buffer (pH 9.2) containing 50 mM SDS and 20 mM gamma-cyclodextrin, all ten of the tested estrogens were separated. However, the cyclodextrin-modified buffer allowed faster separation. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702. NCI,DCE,BETHESDA,MD 20892. NR 34 TC 44 Z9 47 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JAN 20 PY 1995 VL 690 IS 1 BP 149 EP 154 DI 10.1016/0021-9673(94)00990-Q PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA QE703 UT WOS:A1995QE70300017 PM 7881538 ER PT J AU CHAE, MY SWENN, K KANUGULA, S DOLAN, ME PEGG, AE MOSCHEL, RC AF CHAE, MY SWENN, K KANUGULA, S DOLAN, ME PEGG, AE MOSCHEL, RC TI 8-SUBSTITUTED O-6-BENZYLGUANINE, SUBSTITUTED 6(4)-(BENZYLOXY)PYRIMIDINE, AND RELATED DERIVATIVES AS INACTIVATORS OF HUMAN O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID TUMOR XENOGRAFTS; ALKYLATING-AGENTS; O6-BENZYLGUANINE; SENSITIVITY; 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA; DEPLETION AB Several 8-substituted O-6-benzylguanines, 2- and/or 8-substituted 6-(benzyloxy)purines, substituted 6(4)-(benzyloxy)pyrimidines, and a 6-(benzyloxy)-s-triazine were tested for their ability to inactivate the human DNA repair protein, O-6-alkylguanine-DNA alkyltransferase (AGT, alkyltransferase). Two types of compounds were identified as being significantly more-effective than O-6-benzylguanine (the prototype low molecular weight inactivator) at inactivating AGT in human HT29 colon tumor cell extracts. These were 8-substituted O-6-benzylguanines bearing electron-withdrawing groups at the 8-position (e.g. 8-aza-O-6-benzylguanine and O-6-benzyl-8-bromoguanine) and 5-substituted 2,4-diamino-6-(benzyloxy)pyrimidines bearing electron-withdrawing groups at the 5-position (e.g; 2,4-diamino-6-(benzyloxy)-5-nitroso- and 2,4-diamino-(benzyloxy)-5-nitropyrimidine). The latter derivatives were also more effective than O-6-benzylguanine at inactivating AGT in intact HT29 colon tumor cells. Provided these types of purines and pyrimidines do not exhibit undesirable toxicity, they may be superior to O-6-benzylguanine as chemotherapeutic adjuvants for enhancing the effectiveness of antitumor drugs for which the mechanism of action involves modification of the O-6-position of DNA guanine residues. C1 NCI,FREDERICK CANC RES & DEV CTR,CHEM CARCINOGENESIS LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. PENN STATE UNIV,COLL MED,MILTON S HERSHEY MED CTR,DEPT CELLULAR & MOLEC PHYSIOL,HERSHEY,PA 17033. PENN STATE UNIV,COLL MED,MILTON S HERSHEY MED CTR,DEPT PHARMACOL,HERSHEY,PA 17033. UNIV CHICAGO,MED CTR,DIV HEMATOL ONCOL,CHICAGO,IL 60637. FU NCI NIH HHS [N01-CO-46000, CA57725] NR 23 TC 82 Z9 83 U1 2 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JAN 20 PY 1995 VL 38 IS 2 BP 359 EP 365 DI 10.1021/jm00002a018 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA QD218 UT WOS:A1995QD21800018 PM 7830279 ER PT J AU CARROLL, FI KOTIAN, P DEHGHANI, A GRAY, JL KUZEMKO, MA PARHAM, KA ABRAHAM, P LEWIN, AH BOJA, JW KUHAR, MJ AF CARROLL, FI KOTIAN, P DEHGHANI, A GRAY, JL KUZEMKO, MA PARHAM, KA ABRAHAM, P LEWIN, AH BOJA, JW KUHAR, MJ TI COCAINE AND 3-BETA-(4'-SUBSTITUTED PHENYL)TROPANE-2-BETA-CARBOXYLIC ACID ESTER AND AMIDE ANALOGS - NEW HIGH-AFFINITY AND SELECTIVE COMPOUNDS FOR THE DOPAMINE TRANSPORTER SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID I-125 RTI-55; LIGAND-BINDING; SEROTONIN TRANSPORTERS; RECOGNITION SITES; RAT-BRAIN; INHIBITION; RECEPTOR; AUTORADIOGRAPHY; NOREPINEPHRINE; DISEASE AB Several 2 beta-carboxylic acid ester and amide analogues of cocaine and of 3 beta-(4'-substituted phenyl)tropane-2 beta-carboxylic acid were prepared. The binding affinities of these compounds, and of some previously prepared analogues, at the dopamine (DA), norepinephrine (NE), and serotonin (5-HT) transporters were determined. The phenyl esters of 3 beta-(4'-methylphenyl)and 3 beta-(4'-chlorophenyl)trop ane-2 beta-carboxylic acid are highly potent and highly selective for the DA transporter. The isopropyl esters of 3 beta-(4'- chlorophenyl)- and 3 beta-(4'-iodophenyl)tropane-2 beta-carboxylic acid also possess high DA affinity and show significant DA transporter selectivity. Similarly, the phenyl and isopropyl ester analogues of cocaine are much more selective for the DA transporter than cocaine. Tertiary amide analogues of cocaine and of 3 beta-(4'-substituted phenyl)tropane-2 beta-carboxylic acids are more potent inhibitors of radioligand binding at the DA transporter than the primary and secondary amide analogues. In particular, 3 beta-(4'-chlorophenyl)tropane-2 beta-N-morpholinocarboxamide as well as the 3 beta-(4'-chlorophenyl)- and 3 beta-(4'-iodophenyl)tropane-2 beta-N-pyrrolidinocarboxamides possess high affinity and selectivity for the DA transporter. The N,N-dimethylamide cocaine analogue is the most selective cocaine amide derivative for the DA transporter. High correlation between the inhibition of radioligand binding and inhibition of uptake at the DA, NE, and 5-HT transporter was found for a selected group of analogues. Within this group, one compound, the isopropyl ester of 3 beta-(4'-iodophenyl)tropane-2 beta-carboxylic acid, was found to be more potent in the inhibition of radioligand binding than in the inhibition of DA uptake. Taken together with its high potency and selectivity at the DA transporter, this suggests that this compound may be a lead in the development of a cocaine antagonist. C1 NIDA,ADDICT RES CTR,NEUROSCI BRANCH,BALTIMORE,MD 21224. RP CARROLL, FI (reprint author), RES TRIANGLE INST,POB 12194,RES TRIANGLE PK,NC 27709, USA. FU NIDA NIH HHS [DA05477] NR 48 TC 180 Z9 180 U1 2 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JAN 20 PY 1995 VL 38 IS 2 BP 379 EP 388 DI 10.1021/jm00002a020 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA QD218 UT WOS:A1995QD21800020 PM 7830281 ER PT J AU IVANOV, VI MINCHENKOVA, LE CHERNOV, BK MCPHIE, P RYU, S GARGES, S BARBER, AM ZHURKIN, VB ADHYA, S AF IVANOV, VI MINCHENKOVA, LE CHERNOV, BK MCPHIE, P RYU, S GARGES, S BARBER, AM ZHURKIN, VB ADHYA, S TI CRP-DNA COMPLEXES - INDUCING THE A-LIKE FORM IN THE BINDING-SITES WITH AN EXTENDED CENTRAL SPACER SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE CRP; CAMP; DNA CONFORMATION; A-FORM DNA; CIRCULAR DICHROISM ID GENE ACTIVATOR PROTEIN; AMP RECEPTOR PROTEIN; CRYSTAL-STRUCTURE; CIRCULAR-DICHROISM; NUCLEIC-ACID; B-DNA; CAP; RECOGNITION; CONFORMATIONS; TRANSITION AB The consensus DNA sequence for binding of the Escherichia coli cyclic AMP receptor protein (CRP) has two symmetrically related inverted recognition elements TGTGA:TCACA, separated by a variable spacer, normally 6 bp long. We have shown that the CRP-cAMP complex, when bound to synthetic binding sites with an extended 8 bp spacer segment, induces an increase in the DNA circular dichroism (CD). The CD change at lambda > 275 nm agrees with the shift of approximately one helical turn of DNA into A-like form. The B-conformation is preserved for CRP binding sites similar to that in the Inc and uxaCA promoters with 6 bp spacers. Another effect accompanying DNA binding is a dramatic increase of the negative CD magnitude in the spectral region of the ligand cAMP, at lambda < 272 nm. This effect is observed when CRP binds to specific sites with 6 or 8 bp spacers as well as to non-specific DNA. We reason that the A-like form arises by compressing and unwinding the DNA in CRP-DNA complexes having 8 bp central spacers. This serves to maintain a fixed length and twisting angle anal is controlled by the protein's relatively rigid frame. This model is consistent with the observation that some binding sites with 6 bp spacers may also show the CD increase inherent to the sites with the extended 8 bp spacers. These 6 bp spacers are characterized by an increased twisting angle that requires their unwinding to bind to CRP. We propose that a mutual adaptation between CRP and binding sites by local untwisting and a B-->A-like transition in the DNA is of general importance and may occur in other protein-DNA complexes, such as the complex of RNA polymerase with promoter DNA. C1 NCI,BETHESDA,MD 20892. VA ENGELHARDT MOLEC BIOL INST,MOSCOW 117984,RUSSIA. NIDDKD,BETHESDA,MD 20892. NR 36 TC 36 Z9 36 U1 0 U2 3 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JAN 20 PY 1995 VL 245 IS 3 BP 228 EP 240 DI 10.1006/jmbi.1994.0019 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QB064 UT WOS:A1995QB06400004 PM 7844815 ER PT J AU CHACKO, S SILVERTON, E KAMMORGAN, L SMITHGILL, S COHEN, G DAVIES, D AF CHACKO, S SILVERTON, E KAMMORGAN, L SMITHGILL, S COHEN, G DAVIES, D TI STRUCTURE OF AN ANTIBODY LYSOZYME COMPLEX UNEXPECTED EFFECT OF A CONSERVATIVE MUTATION SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE CRYSTAL; ANTIGEN; FAB; MUTANT LYSOZYME ID SITE-DIRECTED MUTAGENESIS; INFLUENZA-VIRUS NEURAMINIDASE; RAY CRYSTAL-STRUCTURE; PANCREATIC TRYPSIN-INHIBITOR; PROTEIN-PROTEIN RECOGNITION; HUMAN-PLASMA KALLIKREIN; AMINO-ACID MUTATION; 3-DIMENSIONAL STRUCTURE; MONOCLONAL-ANTIBODY; CRYSTALLOGRAPHIC REFINEMENT AB The structure of the complex between the Fab HyHEL-5 and chicken lysozyme revealed a large interface region containing 23 lysozyme and 28 Fab residues. Arg68 of the lysozyme is centrally placed in this interface and theoretical studies together with binding assays of this Fab to different avian lysozymes have previously shown that this arginine residue is an important contributor to the binding. The Arg68-->Lys mutant binds 10(3) times less well to the HyHEL-5 Fab. We have examined the refined crystal structure of the complex of this mutant lysozyme with the Fab. No global changes occur, but. there is an introduction of a new water molecule into the interface that mediates the hydrogen bonding interactions between the lysine and residues on the Fab. These data are compared with the effects of similar changes on the inhibition of serine proteases such as trypsin where the energetic effects of this substitution are small. C1 UNIV CALIF BERKELEY,DEPT MOLEC & CELL BIOL,BERKELEY,CA 94720. NCI,BETHESDA,MD 20892. RP CHACKO, S (reprint author), NIDDK,BETHESDA,MD, USA. NR 76 TC 76 Z9 76 U1 0 U2 3 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JAN 20 PY 1995 VL 245 IS 3 BP 261 EP 274 DI 10.1006/jmbi.1994.0022 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QB064 UT WOS:A1995QB06400007 PM 7531245 ER PT J AU BANGA, SS YAMAMOTO, AH MASON, JM BOYD, JB AF BANGA, SS YAMAMOTO, AH MASON, JM BOYD, JB TI MOLECULAR-CLONING OF MEI-41, A GENE THAT INFLUENCES BOTH SOMATIC AND GERMLINE CHROMOSOME METABOLISM OF DROSOPHILA-MELANOGASTER SO MOLECULAR & GENERAL GENETICS LA English DT Article DE DNA REPAIR; MEI-41; TRANSPOSON-TAGGING; P-ELEMENT-MEDIATED TRANSFORMATION; DROSOPHILA MELANOGASTER ID STRAND BREAK REPAIR; X-LINKED MUTANTS; DNA-REPAIR; POSTREPLICATION REPAIR; HYBRID DYSGENESIS; MEIOTIC RECOMBINATION; ROSY LOCUS; MUTATIONS; EXCISION; TRANSPOSITION AB The mei-41 gene of Drosophila melanogaster plays an essential role in meiosis, in the maintenance of somatic chromosome stability, in postreplication repair and in DNA double-strand break repair. This gene has been cytogenetically localized to polytene chromosome bands 14C4-6 using available chromosomal aberrations. About 60 kb of DNA sequence has been isolated following a bidirectional chromosomal walk that extends over the cytogenetic interval 14C1-6. The break-points of chromosomal aberrations identified within that walk establish that the entire mei-41 gene has been cloned. Two independently derived mei-41 mutants have been shown to carry P insertions within a single 2.2 kb fragment of the walk. Since revertants of those mutants have lost the P element sequences, an essential region of the mei-41 gene is present in that fragment. A 10.5 kb genomic fragment that spans the P insertion sites has been found to restore methyl methanesulfonate resistance and female fertility of the mei-41(D3) mutants. The results demonstrate that all the sequences required for the proper expression of the mei-41 gene are present on this genomic fragment. This study provides the foundation for molecular analysis of a function that is essential for chromosome stability in both the germline and somatic cells. C1 UNIV CALIF DAVIS,MOLEC & CELLULAR BIOL SECT,DAVIS,CA 95616. NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. FU NIGMS NIH HHS [GM32040] NR 52 TC 15 Z9 15 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0026-8925 J9 MOL GEN GENET JI Mol. Gen. Genet. PD JAN 20 PY 1995 VL 246 IS 2 BP 148 EP 155 DI 10.1007/BF00294677 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA QE608 UT WOS:A1995QE60800003 PM 7862085 ER PT J AU SANTORO, M CARLOMAGNO, F ROMANO, A BOTTARO, DP DATHAN, NA GRIECO, M FUSCO, A VECCHIO, G MATOSKOVA, B KRAUS, MH DIFIORE, PP AF SANTORO, M CARLOMAGNO, F ROMANO, A BOTTARO, DP DATHAN, NA GRIECO, M FUSCO, A VECCHIO, G MATOSKOVA, B KRAUS, MH DIFIORE, PP TI ACTIVATION OF RET AS A DOMINANT TRANSFORMING GENE BY GERMLINE MUTATIONS OF MEN2A AND MEN2B SO SCIENCE LA English DT Article ID CELLS; PROTOONCOGENE; RECEPTOR; ONCOGENE; KINASE AB Multiple endocrine neoplasia types 2A and 2B (MEN2A and MEN2B) and familial medullary thyroid carcinoma are dominantly inherited cancer syndromes. All three syndromes are associated with mutations in RET, which encodes a receptor-like tyrosine kinase. The altered RET alleles were shown to be transforming genes in NIH 3T3 cells as a consequence of constitutive activation of the RET kinase. The MEN2A mutation resulted in RET dimerization at steady state, whereas the MEN2B mutation altered RET catalytic properties both quantitatively and qualitatively. Oncogenic conversion RET in these neoplastic syndromes establishes germline transmission of dominant transforming genes in human cancer. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. UNIV NAPLES,CNR,CTR ENDOCRINOL & ONCOL SPERIMENTALE,NAPLES,ITALY. UNIV NAPLES,DEPT BIOL & PATOL CELLULARE & MOLEC L CALIFANO,NAPLES,ITALY. NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. FAC MED & CHIRURG CATANZARO,DIPARTIMENTO MED SPERIMENTALE & CLIN,CATANZARO,ITALY. NCI,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. RI Bottaro, Donald/F-8550-2010; Di Fiore, Pier Paolo/K-2130-2012; OI Bottaro, Donald/0000-0002-5057-5334; Di Fiore, Pier Paolo/0000-0002-2252-0950; Fusco, Alfredo/0000-0003-3332-5197 NR 20 TC 649 Z9 656 U1 1 U2 10 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JAN 20 PY 1995 VL 267 IS 5196 BP 381 EP 383 DI 10.1126/science.7824936 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QC273 UT WOS:A1995QC27300036 PM 7824936 ER PT J AU RHEE, CK CHAE, K LEVY, LA KORACH, KS AF RHEE, CK CHAE, K LEVY, LA KORACH, KS TI SYNTHESIS AND ESTROGEN-RECEPTOR BINDING OF FLUORINATED DIETHYLSTILBESTROL DERIVATIVES SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID METABOLITES; ANALOGS AB Synthesis of fluorinated DES and hexestrol derivatives starting from 4-methoxybenzaldehyde is described. The structures of the fluorinated compounds were characterized by NMR. The fluorinated DES derivatives bind to the mouse uterine cytosol estrogen receptor with high affinity. C1 NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. RP RHEE, CK (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Korach, Kenneth/0000-0002-7765-418X NR 16 TC 6 Z9 6 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JAN 19 PY 1995 VL 5 IS 2 BP 133 EP 138 DI 10.1016/0960-894X(94)00472-R PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA QF114 UT WOS:A1995QF11400007 ER PT J AU OIE, T TOPOL, IA BURT, SK AF OIE, T TOPOL, IA BURT, SK TI AB-INITIO AND DENSITY-FUNCTIONAL STUDIES ON INTERNAL-ROTATION AND CORRESPONDING TRANSITION-STATES IN CONJUGATED MOLECULES SO JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article ID ELECTRON CORRELATION-ENERGY; S-CIS-ACROLEIN; ORBITAL METHODS; METHYL ACETATE; BASIS-SETS; CONFORMATIONAL-ANALYSIS; POLYATOMIC-MOLECULES; NONLOCAL CORRECTIONS; THEORETICAL METHODS; PERTURBATION-THEORY AB A comparative study between a high-level ab initio molecular orbital method and density functional theory (DFT) employing local density approximation with nonlocal gradient corrections to the exchange-correlation potential (NLGC) included has been performed on the rotational barriers around the single bond for 11 molecules. Ah of these molecules are constitutive parts of large biomolecules and have single bonds with varying degrees of partial double bond character. All conformers were optimized by the both methods, using comparable basis sets (double zeta plus polarization in valence orbital) including correlation effect, followed by single-point energy calculations using even larger basis sets. An excellent agreement between the two methods was obtained in locating the transition states. Although reasonable agreement between the two methods was obtained for the barriers in non-amide molecules, fairly large discrepancies were found for amide bonds. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK BIOMED SUPERCOMP CTR,FREDERICK,MD 21702. ABBOTT LABS,DEPT 46,ABBOTT PK,IL 60064. NR 74 TC 38 Z9 38 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-3654 J9 J PHYS CHEM-US JI J. Phys. Chem. PD JAN 19 PY 1995 VL 99 IS 3 BP 905 EP 915 DI 10.1021/j100003a012 PG 11 WC Chemistry, Physical SC Chemistry GA QC835 UT WOS:A1995QC83500012 ER PT J AU MACKALL, CL FLEISHER, TA BROWN, MR ANDRICH, MP CHEN, CC FEUERSTEIN, IM HOROWITZ, ME MAGRATH, IT SHAD, AT STEINBERG, SM WEXLER, LH GRESS, RE AF MACKALL, CL FLEISHER, TA BROWN, MR ANDRICH, MP CHEN, CC FEUERSTEIN, IM HOROWITZ, ME MAGRATH, IT SHAD, AT STEINBERG, SM WEXLER, LH GRESS, RE TI AGE, THYMOPOIESIS, AND CD4+ T-LYMPHOCYTE REGENERATION AFTER INTENSIVE CHEMOTHERAPY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BONE-MARROW TRANSPLANTATION; IMMUNODEFICIENCY-VIRUS INFECTION; ISOFORM EXPRESSION; CELL REGENERATION; SUBSETS; THYMECTOMY; DEPLETION; PROGENY; THERAPY; THYMUS AB Background. Inadequate reconstitution of CD4+ T lymphocytes is an important clinical problem complicating chemotherapy, human immunodeficiency virus infection, and bone marrow transplantation, but relatively little is known about how CD4+ T lymphocytes regenerate. There are two main possibilities: bone marrow-derived progenitors could reconstitute the lymphocyte population using a thymus-dependent pathway, or thymus-independent pathways could predominate. Previous studies have suggested that the CD45RA glycoprotein on CD4+ T lymphocytes is a marker for progeny generated by a thymus-dependent pathway. Methods. We studied 15 patients 1 to 24 years of age who had undergone intensive chemotherapy for cancer. The absolute numbers of CD4+ T lymphocytes in peripheral blood and the expression of CD45 isoforms (CD45RA and CD45RO) on these lymphocytes were studied serially during lymphocyte regeneration after the completion of therapy. Radiographic imaging of the thymus was performed concomitantly. Results. There was an inverse relation between the patients' ages and the CD4+ T-lymphocyte counts six months after therapy was completed (r=-0.92). The CD4+ recovery correlated quantitatively with the appearance of CD45RA+CD4+ T lymphocytes in the blood (r=0.64). There was a higher proportion of CD45RA+CD4+ T lymphocytes in patients with thymic enlargement after chemotherapy than in patients without such enlargement (two-sided P=0.015). Conclusions. Thymus-dependent regeneration of CD4+ T lymphocytes occurs primarily in children, whereas even young adults have deficiencies in this pathway. Our results suggest that rapid T-cell regeneration requires residual thymic function in patients receiving high-dose chemotherapy. C1 NCI,DIV CANC BIOL DIAG & CTR,EXPTL IMMUNOL BRANCH,BETHESDA,MD. NCI,DIV CANC TREATMENT,MED BRANCH,BETHESDA,MD. NCI,DIV CANC TREATMENT,PEDIAT BRANCH,BETHESDA,MD. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD. NIH,CTR CLIN,DEPT NUCL MED,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT CLIN PATHOL,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,HENRY M JACKSON FDN ADV MIL MED,BETHESDA,MD. RP MACKALL, CL (reprint author), NIH,CTR CLIN,DEPT RADIOL,BLDG 10,RM 4B14,BETHESDA,MD 20892, USA. NR 28 TC 833 Z9 841 U1 1 U2 6 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 19 PY 1995 VL 332 IS 3 BP 143 EP 149 DI 10.1056/NEJM199501193320303 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA QB160 UT WOS:A1995QB16000003 PM 7800006 ER PT J AU LIN, AY GRIDLEY, G TUCKER, M AF LIN, AY GRIDLEY, G TUCKER, M TI BENIGN ANAL LESIONS AND ANAL CANCER SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP LIN, AY (reprint author), NCI,BETHESDA,MD 20892, USA. RI Tucker, Margaret/B-4297-2015 NR 5 TC 6 Z9 6 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 19 PY 1995 VL 332 IS 3 BP 190 EP 191 DI 10.1056/NEJM199501193320315 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA QB160 UT WOS:A1995QB16000023 PM 7695719 ER PT J AU FORD, H DRISCOLL, JS HAO, Z DOBYNS, KA ROMMEL, ME STOWE, E ANDERSON, JO PLOWMAN, J WAUD, WR JOHNS, DG COONEY, DA AF FORD, H DRISCOLL, JS HAO, Z DOBYNS, KA ROMMEL, ME STOWE, E ANDERSON, JO PLOWMAN, J WAUD, WR JOHNS, DG COONEY, DA TI REVERSAL BY CYTIDINE OF CYCLOPENTENYL CYTOSINE-INDUCED TOXICITY IN MICE WITHOUT COMPROMISE OF ANTITUMOR-ACTIVITY SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE CYCLOPENTENYL CYTOSINE; CYTIDINE; MOLT-4 LYMPHOBLASTS; ANTIDOTES; L1210 LEUKEMIA; ANTIMETABOLITE ID CANCER CELLS; INHIBITION; SYNTHETASE; MODULATION; URIDINE AB Among nine compounds surveyed, cytidine was found to be the most effective in reversing the antiproliferative effects of cyclopentenyl cytosine (CPEC) on human T-lymphoblasts (MOLT-4) in culture. Cytidine, at concentrations of 1-25 mu M, enabled cells to maintain normal logarithmic growth when added up to 12 hr after exposure to a 200 nM concentration of the oncolytic nucleoside, CPEC. The most abundant CPEC metabolite, CPEC-5'-triphosphate, is a potent [K-1 approximate to 6 mu M] inhibitor of CTP synthetase (EC 6.3.4.2). accumulation of this inhibitor resulted in a depletion of CTP levels to 17% of their original cellular concentration. Exogenous cytidine reversed CPEC-induced cellular cytotoxicity by suppressing the formation of CPEC-5'-triphosphate by 70%, and by partially replenishing intracellular CTP to at least 60-70% of its original concentration. In vivo, cytidine (500 mg/kg) administered intraperitoneally 4 hr after each daily dose of CPEC (LD(10)-LD(100)) for 9 days reduced the toxicity and abolished the lethality of CPEC to non-tumored mice. Of greater practical importance is the finding that, under these experimental conditions, cytidine did not curtail the antineoplastic properties of CPEC in L1210 tumor-bearing mice. Moreover, the concentration range over which CPEC exhibited antineoplastic activity was extended with cytidine administration. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BIOL TESTING BRANCH,BETHESDA,MD 20892. SO RES INST,BIRMINGHAM,AL 35255. RP FORD, H (reprint author), NCI,MED CHEM LAB,BLDG 37,ROOM 5C-24,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 24 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JAN 18 PY 1995 VL 49 IS 2 BP 173 EP 180 DI 10.1016/S0006-2952(94)00490-0 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QE673 UT WOS:A1995QE67300006 PM 7840794 ER PT J AU CYSYK, RL MALINOWSKI, N MARQUEZ, V ZAHAREVITZ, D AUGUST, EM MOYER, JD AF CYSYK, RL MALINOWSKI, N MARQUEZ, V ZAHAREVITZ, D AUGUST, EM MOYER, JD TI CYCLOPENTENYL URACIL - AN EFFECTIVE INHIBITOR OF URIDINE SALVAGE IN-VIVO SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE CYCLOPENTENYL URACIL; URIDINE; INHIBITION OF PYRIMIDINE SALVAGE IN VIVO ID N-(PHOSPHONACETYL)-L-ASPARTIC ACID PALA; CIRCULATING PYRIMIDINE NUCLEOSIDES; TRANSPORT; MOUSE; SERUM; MICE; DIPYRIDAMOLE; TISSUES; INVIVO; KINASE AB Cyclopentenyl uracil, a non-cytotoxic inhibitor of uridine kinase, was found to effectively block the salvage of circulating uridine by host and tumor tissues in the intact mouse. Dose-response characteristics of the inhibition were determined. Large doses (1 g/kg) of cyclopentenyl uracil were required, and the effect of a single dose fell rapidly over a 24-hr period. A sustained inhibition of uridine salvage of >64-79% could be maintained by multiple doses of 1 g/kg given on an every 8-hr schedule. Mice given cyclopentenyl uracil (1 g/kg) every 8 hr for 5 days continued to gain weight and showed no signs of toxicity; however, the combination of cyclopentenyl uracil with a non-toxic dose of N-(phosphonacetyl)-L-aspartic acid (PALA; 200 mg/kg daily for 5 days) was lethal to mice, indicating that circulating uridine modifies the toxicity of agents that act on enzymes of the de novo pyrimidine pathway. Although the duration of action and potency of cyclopentenyl uracil are not ideal, this is the first demonstration of an effective inhibition of uridine salvage in the intact mouse with a non-cytotoxic agent. This makes possible the evaluation of concurrent inhibition of de novo and salvage routes to pyrimidine nucleotides as an approach to chemotherapy. RP CYSYK, RL (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BIOCHEM SECT,MED CHEM LAB,BLDG 37,ROOM 5E-18,BETHESDA,MD 20892, USA. NR 21 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JAN 18 PY 1995 VL 49 IS 2 BP 203 EP 207 DI 10.1016/0006-2952(94)00470-6 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QE673 UT WOS:A1995QE67300010 PM 7840797 ER PT J AU MILLER, VT LAROSA, J BARNABEI, V KESSLER, C LEVIN, G SMITHROTH, A GRIFFIN, M STOY, DB BUSH, T ZACUR, H FOSTER, D ANDERSON, J MCKENZIE, A MILLER, S WOOD, PD STEFANICK, ML MARCUS, R AKANA, A HEINRICHS, L KIRCHNER, C OHANLAN, K RUYLE, M SHEEHAN, M JUDD, HL GREENDALE, G BAYALOS, R LOZANO, K KAWAKAMI, K BARRETTCONNOR, E LANGER, R KRITZSILVERSTEIN, D CARRIONPETERSEN, ML CAVERO, C SCHROTT, HG JOHNSON, SR FEDDERSEN, DA KRUTZFELDT, DL BENDA, JA PAUERSTEIN, C TRABAL, J SCHENKEN, R STERN, MP RODRIGUEZSIFUENTES, M EASTON, C WELLS, HB ESPELAND, M HOWARD, G BYINGTON, R LEGAULT, C SHUMAKER, S HOGAN, P HIRE, D WASILAUSKAS, C JAMES, M LANE, K TERRELL, T REECE, S PIERCE, J SNOW, M ANTHONY, S MEBANESIMS, IL EINHORN, P HUNSBERGER, S WACLAWIW, M LIPPEL, K LUCAS, D VERTER, J JACKSON, S KELAGHAN, J PERLMAN, J WOLF, P MCGOWAN, J GORDON, S HEYSE, S FRADKIN, J SHERMAN, S PAGE, L SORENSON, A HULKA, B BRODY, B BURKMAN, R HEANEY, R KRAUSS, R ROBERTS, H WITTES, J RIGGS, L MOSS, R ALBERS, J MARCOVINA, S FINEBERG, SE TRACY, RP MERINO, M SCULLY, R LIVOLSI, V KESSLER, G AF MILLER, VT LAROSA, J BARNABEI, V KESSLER, C LEVIN, G SMITHROTH, A GRIFFIN, M STOY, DB BUSH, T ZACUR, H FOSTER, D ANDERSON, J MCKENZIE, A MILLER, S WOOD, PD STEFANICK, ML MARCUS, R AKANA, A HEINRICHS, L KIRCHNER, C OHANLAN, K RUYLE, M SHEEHAN, M JUDD, HL GREENDALE, G BAYALOS, R LOZANO, K KAWAKAMI, K BARRETTCONNOR, E LANGER, R KRITZSILVERSTEIN, D CARRIONPETERSEN, ML CAVERO, C SCHROTT, HG JOHNSON, SR FEDDERSEN, DA KRUTZFELDT, DL BENDA, JA PAUERSTEIN, C TRABAL, J SCHENKEN, R STERN, MP RODRIGUEZSIFUENTES, M EASTON, C WELLS, HB ESPELAND, M HOWARD, G BYINGTON, R LEGAULT, C SHUMAKER, S HOGAN, P HIRE, D WASILAUSKAS, C JAMES, M LANE, K TERRELL, T REECE, S PIERCE, J SNOW, M ANTHONY, S MEBANESIMS, IL EINHORN, P HUNSBERGER, S WACLAWIW, M LIPPEL, K LUCAS, D VERTER, J JACKSON, S KELAGHAN, J PERLMAN, J WOLF, P MCGOWAN, J GORDON, S HEYSE, S FRADKIN, J SHERMAN, S PAGE, L SORENSON, A HULKA, B BRODY, B BURKMAN, R HEANEY, R KRAUSS, R ROBERTS, H WITTES, J RIGGS, L MOSS, R ALBERS, J MARCOVINA, S FINEBERG, SE TRACY, RP MERINO, M SCULLY, R LIVOLSI, V KESSLER, G TI EFFECTS OF ESTROGEN OR ESTROGEN/PROGESTIN REGIMENS ON HEART-DISEASE RISK-FACTORS IN POSTMENOPAUSAL WOMEN - THE POSTMENOPAUSAL ESTROGEN/PROGESTIN INTERVENTIONS (PEPI) TRIAL SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HORMONE-REPLACEMENT THERAPY; DENSITY LIPOPROTEIN CHOLESTEROL; ATHEROSCLEROTIC VASCULAR-DISEASE; ACUTE MYOCARDIAL-INFARCTION; CARDIOVASCULAR-DISEASE; PROGESTOGEN REPLACEMENT; CARBOHYDRATE-METABOLISM; PLASMA-LIPOPROTEIN; INSULIN-RESISTANCE; SERUM-LIPIDS AB Objective.-To assess pairwise differences between placebo, unopposed estrogen, and each of three estrogen/progestin regimens on selected heart disease risk factors in healthy postmenopausal women. Design.-A 3-year, multicenter, randomized, double-blind, placebo-controlled trial. Participants.-A total of 875 healthy postmenopausal women aged 45 to 64 years who had no known contraindication to hormone therapy. Intervention.-Participants were randomly assigned in equal numbers to the following groups: (1) placebo; (2) conjugated equine estrogen (CEE), 0.625 mg/d; (3) CEE, 0.625 mg/d plus cyclic medroxyprogesterone acetate (MPA), 10 mg/d for 12 d/mo; (4) CEE, 0.625 mg/d plus consecutive MPA, 2.5 mg/d; or (5) CEE, 0.625 mg/d plus cyclic micronized progesterone (MP), 200 mg/d for 12 d/mo. Primary Endpoints.-Four endpoints were chosen to represent four biological systems related to the risk of cardiovascular disease: (1) high-density lipoprotein cholesterol (HDL-C), (2) systolic blood pressure, (3) serum insulin, and (4) fibrinogen. Analysis.-Analyses presented are by intention to treat. P values for primary endpoints are adjusted for multiple comparisons; 95% confidence intervals around estimated effects were calculated without this adjustment. Results.-Mean changes in HDL-C segregated treatment regimens into three statistically distinct groups: (1) placebo (decrease of 0.03 mmol/L [1.2 mg/dL]); (2) MPA regimens (increases of 0.03 to 0.04 mmol/L [1.2 to 1.6 mg/dl]); and (3) CEE with cyclic MP (increase of 0.11 mmol/L [4.1 mg/dL]) and CEE alone (increase of 0.14 mmol/L [5.6 mg/dL]). Active treatments decreased mean low-density lipoprotein cholesterol (0.37 to 0.46 mmol/L [14.5 to 17.7 mg/dL]) and increased mean triglyceride (0.13 to 0.15 mmol/L [11.4 to 13.7 mg/dL]) compared with placebo. Placebo was associated with a significantly greater increase in mean fibrinogen than any active treatment (0.10 g/L compared with -0.02 to 0.06 g/L); differences among active treatments were not significant. Systolic blood pressure increased and postchallenge insulin levels decreased during the trial, but neither varied significantly by treatment assignment. Compared with other active treatments, unopposed estrogen was associated with a significantly increased risk of adenomatous or atypical hyperplasia (34% vs 1%) and of hysterectomy (6% vs 1%). No other adverse effect differed by treatment assignment or hysterectomy status. Conclusions.-Estrogen alone or in combination with a progestin improves lipoproteins and lowers fibrinogen levels without detectable effects on postchallenge insulin or blood pressure. Unopposed estrogen is the optimal regimen for elevation of HDL-C, but the high rate of endometrial hyperplasia restricts use to women without a uterus. In women with a uterus, CEE with cyclic MP has the most favorable effect on HDL-C and no excess risk of endometrial hyperplasia. C1 JOHNS HOPKINS UNIV,BALTIMORE,MD. STANFORD UNIV,STANFORD,CA. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. UNIV CALIF SAN DIEGO,SAN DIEGO,CA. IOWA STATE UNIV SCI & TECHNOL,AMES,IA. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. BOWMAN GRAY SCH MED,WINSTON SALEM,NC. NICHHD,BETHESDA,MD. NIAMSD,BETHESDA,MD. NIDDKD,BETHESDA,MD. NIA,BETHESDA,MD. US PHS,CTR SUPPLY SERV,CTR DRUG DISTRIBUT,PERRY POINT,MD. NW LIPID RES CTR,LIPID LAB,SEATTLE,WA. WISHARD MEM HOSP,GLUCOSE INSULIN LAB,INDIANAPOLIS,IN. UNIV VERMONT,HEMOSTASIS LAB,BURLINGTON,VT. NCI,PATHOL LAB,BETHESDA,MD. MASSACHUSETTS GEN HOSP,BOSTON,MA. JEWISH HOSP ST LOUIS,ST LOUIS,MO. GEORGE WASHINGTON UNIV,WASHINGTON,DC. NHLBI,BETHESDA,MD 20892. NR 58 TC 1670 Z9 1690 U1 4 U2 35 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 18 PY 1995 VL 273 IS 3 BP 199 EP 208 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA QB234 UT WOS:A1995QB23400023 ER PT J AU ALLEGRA, CJ AF ALLEGRA, CJ TI NEW THERAPEUTIC STRATEGIES FOR PATIENTS WITH GASTROINTESTINAL MALIGNANCIES USING BIOCHEMICAL MODULATION OF FLUOROURACIL SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Discussion ID HUMAN THYMIDYLATE SYNTHASE; ADVANCED COLORECTAL-CARCINOMA; HIGH-DOSE LEUCOVORIN; COLON-CARCINOMA; INTERFERON ALFA-2A; ADJUVANT THERAPY; FOLINIC ACID; PHASE-II; 5-FLUOROURACIL; CANCER RP ALLEGRA, CJ (reprint author), NATL NAVAL MED CTR, NCI,NAVY MED ONCOL BRANCH,8901 WISCONSIN AVE, BLDG 8, ROOM 5101, BETHESDA, MD 20889 USA. NR 34 TC 5 Z9 5 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 18 PY 1995 VL 273 IS 3 BP 236 EP 239 DI 10.1001/jama.273.3.236 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA QB234 UT WOS:A1995QB23400029 PM 7807664 ER PT J AU KESSLER, LG AF KESSLER, LG TI LUNG-CANCER RATES IN US WOMEN SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material RP KESSLER, LG (reprint author), NCI,APPL RES BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 18 PY 1995 VL 87 IS 2 BP 79 EP 79 DI 10.1093/jnci/87.2.79 PG 1 WC Oncology SC Oncology GA QB157 UT WOS:A1995QB15700004 ER PT J AU FOGLER, WE PEARSON, JW VOLKER, K ARIYOSHI, K WATABE, H RIGGS, CW WILTROUT, RH LONGO, DL AF FOGLER, WE PEARSON, JW VOLKER, K ARIYOSHI, K WATABE, H RIGGS, CW WILTROUT, RH LONGO, DL TI ENHANCEMENT BY RECOMBINANT HUMAN INTERFERON-ALFA OF THE REVERSAL OF MULTIDRUG-RESISTANCE BY MRK-16 MONOCLONAL-ANTIBODY SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID P-GLYCOPROTEIN EXPRESSION; MDR1 GENE-EXPRESSION; ALPHA-INTERFERON; BREAST-CANCER; CELL-LINES; IMMUNOHISTOCHEMICAL DETECTION; DOXORUBICIN RESISTANCE; DRUG-RESISTANCE; TUMOR XENOGRAFT; CARCINOMA CELLS AB Background: The anti-P-glycoprotein monoclonal antibody MRK-16 mediates the reversal of multidrug resistance. Recombinant human interferon alfa (rHuIFN alpha) enhances the cytotoxic activity of diverse chemotherapeutics and may modulate multidrug resistance. Purpose: Our purpose was to determine the outcome of combination treatment with MRK-16, rHuIFN alpha-2a, and cytotoxic agents on tumor cells that express P-glycoprotein (Pgp). Methods: Three Pgp-expressing, multidrug-resistant human tumor cell lines were used: the MDR1 retrovirus-infected HT-29 colon adenocarcinoma (HT-29(mdr1)), the doxorubicin (Adriamycin)-resistant MCF-7 (Adr(R) MCF-7) breast carcinoma, and the de novo Pgp-acquired, HCT-15 colon carcinoma. The parental cell lines HT-29(par) and MCF-7 were used as controls. The in vitro effects of MRK-16 and rHuIFN alpha-2a were studied on: (a) chemosensitivity of parental and multidrug-resistant cell lines to vincristine, doxorubicin, or paclitaxel (Taxol); (b) intracellular drug concentrations; and (c) Pgp expression, The efficacy of vincristine alone or in combination with MRK-16 and/or rHuIFN alpha-2a was assessed against HT-29(mdr1) cells in female, athymic NCr-nu/nu mice. Results: For vincristine, the IC50 (i.e., the concentration that causes 50% inhibition of cell growth) was 7.0 ng/mL in HT-29(mdr1) cells. Pretreatment of HT-29(mdr1) cells with MRK-16 partially restored vincristine sensitivity (IC50 = 4.8 ng/mL), which was enhanced by noncytotoxic concentrations of rHuIFN alpha-2a (IC50 = 2.9 ng/mL) via a mechanism independent of Pgp modulation or [H-3]vincristine efflux, rHuIFN alpha-2a potentiated MRK-16 reversal of multidrug resistance with both doxorubicin and paclitaxel on HT-29(mdr1) cells and with vincristine on Adr(R) MCF-7 and HCT-15 tumor cells. Treatment of mice with 1 mg/kg vincristine weekly for 3 weeks, beginning 10 days after tumor injection, significantly increased the median survival times of the HT-29(par) tumor-bearing mice (60 days versus 35 days; P<.0001) but was only marginally therapeutic for HT-29(mdr1) tumor-bearing mice (52 days versus 46 days), Pretreatment with MRK-16 (500 mu g) and rHuIFN alpha-2a (5 x 10(4) U), alone or in combination, 24 hours before vincristine therapy did not affect the survival of HT-29(par) tumor-bearing mice, In contrast, the survival of mice bearing HT-29(mdr1) tumors was significantly increased following treatment with MRK-16 before vincristine (80 days; P<.0001). Administration of a nontherapeutic dose of rHuIFN alpha-2a (5 x 10(4) U) with MRK-16 before vincristine treatment further increased the median survival times of HT-29(mdr1) tumor-bearing mice (116 days; P<.0001). Conclusions: MRK-16 used in combination with rHuIFN alpha-2a was significantly more effective than MRK-16 in overcoming multidrug resistance. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. HOECHST JAPAN LTD,CELL BIOL LAB,KAWAGOE,SAITAMA 35011,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,DATA MANAGEMENT SERV INC,FREDERICK,MD. RP FOGLER, WE (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,BLDG 560,FREDERICK,MD 21702, USA. NR 51 TC 19 Z9 21 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 18 PY 1995 VL 87 IS 2 BP 94 EP 104 DI 10.1093/jnci/87.2.94 PG 11 WC Oncology SC Oncology GA QB157 UT WOS:A1995QB15700007 PM 7707396 ER PT J AU BROWN, LM SWANSON, CA GRIDLEY, G SWANSON, GM SCHOENBERG, JB GREENBERG, RS SILVERMAN, DT POTTERN, LM HAYES, RB SCHWARTZ, AG LIFF, JM FRAUMENI, JF HOOVER, RN AF BROWN, LM SWANSON, CA GRIDLEY, G SWANSON, GM SCHOENBERG, JB GREENBERG, RS SILVERMAN, DT POTTERN, LM HAYES, RB SCHWARTZ, AG LIFF, JM FRAUMENI, JF HOOVER, RN TI ADENOCARCINOMA OF THE ESOPHAGUS - ROLE OF OBESITY AND DIET SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BARRETTS ESOPHAGUS; REFLUX ESOPHAGITIS; PHARYNGEAL CANCER; GASTRIC CARDIA; VEGETABLES; BLACKS; HERNIA; FRUIT; RISK AB Background: In the United States, the incidence of adenocarcinoma of the esophagus, including the esophagogastric junction, has been increasing rapidly over the past two decades, Except for an association with Barrett's esophagus, little is known about the etiology of these cancers. Purpose: Our purpose was to investigate dietary and nutritional risk factors for adenocarcinoma of the esophagus. Methods: A population-based, case-control interview study of 174 white men with adenocarcinoma of the esophagus and 750 control subjects living in three areas of the United States was conducted during 1986 through 1989, Results: Risk was significantly elevated for subjects in the heaviest quartile compared with the lightest quartile of body mass index (odds ratio [OR] = 3.1; 95% confidence interval [CI] = 1.8-5.3), No significant associations were seen with total calories from food, number of meals eaten per day, level of fat intake, or consumption of coffee and tea. Risks were highest for those consuming the least amount of vegetables, with some evidence of a dose response for the subcategories of cruciferous vegetables (P for trend <.001) and vegetables consumed raw (P for trend = .10), A significantly elevated risk was also seen for those consuming the least amount of raw fruit (P for trend = .05), No clear associations were reported for intake of particular micronutrients overall or in supplements, but a significant protective effect was associated with increasing intake of dietary fiber (P for trend = .004). Conclusions: The findings of an increased risk with obesity and decreased risks with intake of raw fruits and vegetables and dietary fiber provide useful directions to pursue in further investigations of this malignancy, Implications: The finding with respect to obesity is particularly noteworthy, since it may explain at least a portion of the recent epidemic increases reported in the incidence of this tumor. C1 MICHIGAN STATE UNIV,COLL HUMAN MED,E LANSING,MI 48824. NEW JERSEY STATE DEPT HLTH,SPECIAL EPIDEMIOL PROGRAM,TRENTON,NJ. EMORY UNIV,SCH PUBL HLTH,DIV EPIDEMIOL,ATLANTA,GA. UNIV PITTSBURGH,SCH MED,DEPT CLIN EPIDEMIOL & FAMILY MED,PITTSBURGH,PA. RP BROWN, LM (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,RM 415,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01CP51092, N01CP51090, N01CP51089] NR 25 TC 272 Z9 275 U1 0 U2 5 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 18 PY 1995 VL 87 IS 2 BP 104 EP 109 PG 6 WC Oncology SC Oncology GA QB157 UT WOS:A1995QB15700008 PM 7707381 ER PT J AU SELA, S HUSAIN, SR PEARSON, JW LONGO, DL RAHMAN, A AF SELA, S HUSAIN, SR PEARSON, JW LONGO, DL RAHMAN, A TI REVERSAL OF MULTIDRUG-RESISTANCE IN HUMAN COLON-CANCER CELLS EXPRESSING THE HUMAN MDR1 GENE BY LIPOSOMES IN COMBINATION WITH MONOCLONAL-ANTIBODY OR VERAPAMIL SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ASCITES TUMOR-CELLS; P-GLYCOPROTEIN; ENCAPSULATED DOXORUBICIN; CARDIOLIPIN LIPOSOMES; THERAPEUTIC EFFICACY; TRANSGENIC MICE; ADRIAMYCIN; DRUG; VINCRISTINE; LINES AB Background: colorectal cancer is a major cause of cancer-related mortality in the world and the second leading cause of neoplastic death in the United States. A major obstacle in the chemotherapy of this neoplasm is the emergence of multidrug resistance that is frequently associated with the expression of P-glycoprotein (p170) encoded by MDR1 (also known as PGY1) genes. Previously, we demonstrated that liposome-encapsulated doxorubicin is more cytotoxic than free doxorubicin in human promyelocytic leukemia and human breast cancer cells with the multidrug-resistant phenotype. Purpose: Our purpose was to investigate modulation of multidrug resistance by liposome-encapsulated vincristine (VCR) in a drug-resistant human colon cancer cell line HT-29mdr1 cells were exposed to free VCR or liposome-encapsulated VCR alone or in combination with MRK-16 or verapamil. Cytotoxicity of cells after various treatments was determined by neutral red staining, and cellular content of VCR was measured by using radiolabeled VCR;p170 expression of cells was assessed by azidopine. Results: HT-29mdr1 cells express a high amount of p170, thus conferring sixfold to sevenfold resistance to VCR compared with the parent cell line. Liposome-encapsulated VCR lowers drug resistance in HT-29mdr1 cells fourfold; IC50 values (concentration that causes 50% reduction in cell number) were 12.5 +/- 2.5 ng/mL compared with 42.5 +/- ng/mL with free VCR. IC50 values for free VCR with empty liposomes were 25 +/- 1.25 ng/mL. The combination of MRK-16 and free VCR produced a twofold increase in cytoxicity over free VCR in p170-expressing cells; the combination of MRK-16 and liposome-encapsulated VCR produced a 10-fold potentiation of cytoxicity. Nonspecific monoclonal antibody NR-LU-10 had no effect on cytotoxicity of HT-29mdr1 cells with free VCR or liposome-encapsulated VCR. The combination of 1.5 muM verapamil potentiated the cytotoxicity of free VCR ninefold to 10-fold, IC50 values reduced to 5.0 +/- 1.5 ng/mL, and in combination with liposome-encapsulated VCR, IC50 values reduced to 2.5 +/- 1.0 ng/mL, demonstrating a 15- to 17- fold potentiation of cytotoxicity. There were no significant differences in drug accumulation in HT-29mdr1 cells when treated with liposome-encapsulated VCR or free VCR. Liposomes inhibited the photo affinity labeling of azidopine to p170 HT-29mdr1 cells. Conclusions: Liposome encapsulation of VCR effectively modulates multidrug resistance in human colon cancer cells and may become an important modality in treatment for colon cancers. C1 GEORGETOWN UNIV,DEPT MED,WASHINGTON,DC. GEORGETOWN UNIV,LOMBARDI CANC RES CTR,DIV HEMATOL,WASHINGTON,DC. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NR 41 TC 21 Z9 21 U1 0 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 18 PY 1995 VL 87 IS 2 BP 123 EP 128 DI 10.1093/jnci/87.2.123 PG 6 WC Oncology SC Oncology GA QB157 UT WOS:A1995QB15700011 PM 7707383 ER PT J AU HOLMLUND, JT KOPP, WC WILTROUT, RH LONGO, DL URBA, WJ JANIK, JE SZNOL, M CONLON, KC FENTON, RG HORNUNG, R MADARA, K SHIELDS, MA SMITH, JW SHARFMAN, W STEIS, RG EWEL, C MALSPEIS, L CREEKMORE, SP AF HOLMLUND, JT KOPP, WC WILTROUT, RH LONGO, DL URBA, WJ JANIK, JE SZNOL, M CONLON, KC FENTON, RG HORNUNG, R MADARA, K SHIELDS, MA SMITH, JW SHARFMAN, W STEIS, RG EWEL, C MALSPEIS, L CREEKMORE, SP TI A PHASE-I CLINICAL-TRIAL OF FLAVONE-8-ACETIC ACID IN COMBINATION WITH INTERLEUKIN-2 SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Note ID FLAVONE ACETIC-ACID; ADVANCED MALIGNANT-MELANOMA; MURINE RENAL-CANCER; NATURAL-KILLER ACTIVITY; CYTOKINE GENE-EXPRESSION; HUMAN PERIPHERAL-BLOOD; RECOMBINANT INTERLEUKIN-2; CELL-ACTIVITY; INTERFERON-GAMMA; FAA C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,CLIN SERV PROGRAM,FREDERICK,MD 21702. FREDERICK MEM HOSP,FREDERICK,MD. RP HOLMLUND, JT (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,CLIN RES BRANCH,BLDG 1052,FREDERICK,MD 21702, USA. NR 28 TC 5 Z9 5 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 18 PY 1995 VL 87 IS 2 BP 134 EP 136 DI 10.1093/jnci/87.2.134 PG 3 WC Oncology SC Oncology GA QB157 UT WOS:A1995QB15700013 PM 7707385 ER PT J AU RABINOVITZ, M AF RABINOVITZ, M TI CONSEQUENCES OF AMINO-ACID DEPRIVATION IN COMBINATION CHEMOTHERAPY SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID L-HISTIDINOL; INDOLEAMINE 2,3-DIOXYGENASE; PROTEIN-SYNTHESIS; 5-FLUOROURACIL; CANCER; CELLS; INTERFERON; METABOLISM; GLYCOLYSIS; GAMMA RP RABINOVITZ, M (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BLDG 37,RM 5C25,BETHESDA,MD 20892, USA. NR 18 TC 2 Z9 2 U1 1 U2 3 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JAN 18 PY 1995 VL 87 IS 2 BP 142 EP 143 DI 10.1093/jnci/87.2.142 PG 2 WC Oncology SC Oncology GA QB157 UT WOS:A1995QB15700015 PM 7707386 ER PT J AU DANESI, R MCLELLAN, CA MYERS, CE AF DANESI, R MCLELLAN, CA MYERS, CE TI SPECIFIC LABELING OF ISOPRENYLATED PROTEINS - APPLICATION TO STUDY INHIBITORS OF THE POSTTRANSLATIONAL FARNESYLATION AND GERANYLGERANYLATION SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID SELECTIVE-INHIBITION; RAS; TISSUES; CELLS AB Specific labeling of either farnesylated or geranylgeranylated proteins in human PC-3 prostate cancer cell line was obtained by suppression of mevalonic acid biosynthesis with lovastatin, 50 mu M,followed by supplementation of cell culture medium with either [H-3]farnesyl- or [H-3]geranylgeranyl-pyrophosphate. The immunoprecipitation of either a farnesylated (p21 ras) or geranylgeranylated (p21 rap 1) protein demonstrated that labeling was specific since proteins were detected only if the appropriate isoprenoid was added to the culture medium. TLC analysis indicated that no conversion of one isoprenoid to the other occurred in these conditions. The selective labeling of either farnesylated or geranylgeranylated proteins may be a valuable tool for the development of inhibitors of isoprenoid transferases as a potential new class of antitumor agents. (C) 1995 Academic Press, Inc. C1 NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. RP DANESI, R (reprint author), UNIV VIRGINIA,DIV HEMATOL ONCOL,BLDG MR-4,BOX 1131,CHARLOTTESVILLE,VA 22908, USA. NR 18 TC 42 Z9 43 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 17 PY 1995 VL 206 IS 2 BP 637 EP 643 DI 10.1006/bbrc.1995.1090 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QC115 UT WOS:A1995QC11500029 PM 7826382 ER PT J AU YOO, SH LEWIS, MS AF YOO, SH LEWIS, MS TI THERMODYNAMIC STUDY OF THE PH-DEPENDENT INTERACTION OF CHROMOGRANIN-A WITH AN INTRALUMINAL LOOP PEPTIDE OF THE INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR SO BIOCHEMISTRY LA English DT Article ID ISOLATED CHROMAFFIN VESICLES; C-TERMINAL REGION; TRISPHOSPHATE RECEPTOR; CONFORMATIONAL CHANGE; COIL TRANSITION; INSP3 RECEPTOR; PROTEIN; BINDING; PURIFICATION; EXPRESSION AB The secretory vesicles of adrenal chromaffin cells have previously been identified as a major inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ store, and their Ca2+ store role has been attributed to the presence of chromogranin A, a high capacity, low affinity Ca2+ binding protein. Chromogranin A has since been shown to exist primarily in a dimeric state at pH 7.5 and primarily in a tetrameric state at the intravesicular pH of 5.5 and has also been shown to interact with the membrane proteins of secretory vesicles at pH 5.5, including a 260-kDa protein reactive to IP3 receptor antibody [Yoo, S. H. (1994) J. Biol. Chem. 269, 12001-12006]. In a recent study, chromogranin A was shown to interact with one of the intraluminal loop regions of the IP3 receptor at pH 5.5 but not at pH 7.5 [Yoo, S. Il., and Lewis, M. S. (1994) FEES Lett. 341, 28-32]. To gain further insight, we have studied the temperature dependence of the pH-dependent interaction of chromogranin A with the intraluminal peptide of the the IP3 receptor by analytical ultracentrifugation, using multiwavelength scan analysis, and found that four molecules of the intraluminal domain peptide of the IP3 receptor bound to each chromogranin A tetramer with Delta G degrees values ranging from -23.6 to -27.6 kcal mol(-1) in the absence and presence of 35 mM Ca2+. In the presence of 35 mM Ca2+, the interaction between chromogranin A tetramer and the intraluminal domain peptide of the IP3 receptor showed Delta G degrees values of increasing magnitude as the temperature was increased while the same interaction in the absence of Ca2+ showed Delta G degrees values of decreasing magnitude. Further, the values for the Delta H degrees and Delta S degrees of the interaction increased in the absence of Ca2+ but decreased in the presence of 35 mM Ca2+ as the temperature was increased, indicating the stabilizing effect of Ca2+ on the interaction. C1 NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RP YOO, SH (reprint author), NIDOCD,CELLULAR BIOL LAB,BLDG 36,ROOM 5D-13,BETHESDA,MD 20892, USA. NR 30 TC 41 Z9 41 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JAN 17 PY 1995 VL 34 IS 2 BP 632 EP 638 DI 10.1021/bi00002a030 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QB821 UT WOS:A1995QB82100030 PM 7819258 ER PT J AU HSING, AW MCLAUGHLIN, JK OLSEN, JH MELLEMKJAR, L WACHOLDER, S FRAUMENI, JF AF HSING, AW MCLAUGHLIN, JK OLSEN, JH MELLEMKJAR, L WACHOLDER, S FRAUMENI, JF TI CANCER RISK FOLLOWING PRIMARY HEMOCHROMATOSIS - A POPULATION-BASED COHORT STUDY IN DENMARK SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID PRIMARY LIVER-CANCER; IDIOPATHIC HEMOCHROMATOSIS; GENETIC HEMOCHROMATOSIS; CIRRHOSIS AB A population-based cohort of 120 Danish men, discharged with a hospital diagnosis of primary hemochromatosis from 1977 to 1989, was followed up to 1989 for subsequent cancer risk. Nineteen subjects (including 6 with primary liver cancers) were excluded from the analysis, either because they died within the same month of hemochromatosis diagnosis or because they had cancer prior to diagnosis of hemochromatosis. Among the 101 remaining subjects, 4 primary liver cancers occurred one year or more after the diagnosis of hemochromatosis, far surpassing the expected number based on incidence rates from the Danish population (standardized incidence ratio 92.9, 95% confidence interval 25.0 to 237.9). The excess of liver cancer was associated with cirrhosis and included cholangiocarcinoma as well as hepatocellular carcinoma. Significantly elevated risks were also observed for non-hepatic cancers (13 cases; SIR 3.5, 95% CI 1.9 to 6.0), notably esophageal cancer (2 cases; SIR 42.9, 95% CI 4.8 to 154.9) and skin melanoma (2 cases; SIR 27.8, 95% CI 3.1 to 100.3). The results of this population-based study are in accordance with the hypothesis that patients with primary hemochromatosis have a substantial risk of primary liver cancer. Further studies of hemochromatosis may be useful in clarifying the relation of non-hepatic malignancies to body iron stores in the general population. (C) 1995 Wiley-Liss, Inc.(*) C1 DANISH CANC SOC,DIV CANC EPIDEMIOL,COPENHAGEN,DENMARK. RP HSING, AW (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EPN 415,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 15 TC 96 Z9 100 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 17 PY 1995 VL 60 IS 2 BP 160 EP 162 DI 10.1002/ijc.2910600204 PG 3 WC Oncology SC Oncology GA QH518 UT WOS:A1995QH51800003 PM 7829208 ER PT J AU MCLAUGHLIN, JK HRUBEC, Z BLOT, WJ FRAUMENI, JF AF MCLAUGHLIN, JK HRUBEC, Z BLOT, WJ FRAUMENI, JF TI SMOKING AND CANCER MORTALITY AMONG US VETERANS - A 26-YEAR FOLLOW-UP SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID UNITED-STATES VETERANS; CIGARETTE-SMOKING; TOBACCO USE; CARCINOMA AB On the 30th anniversary of the U.S. Surgeon General's report Smoking and Health, we present updated results from one of the original cohort studies that comprised the groundbreaking document. A 26-year follow-up of 248,046 U.S. veterans evaluating the risks of cigarette smoking revealed strong dose-response effects between smoking and total cancer and a large number of cancer sites. Over 50% of cancer deaths among current smokers and 23% of cancer deaths among former smokers were attributable to cigarette smoking. These findings further demonstrate the large and unique role cigarette smoking plays in cancer etiology and the importance of smoking cessation to reduce this enormous public health burden. (C) 1995 Wiley-Liss, Inc.(*) C1 NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,ROCKVILLE,MD 20852. NR 26 TC 127 Z9 132 U1 2 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 17 PY 1995 VL 60 IS 2 BP 190 EP 193 PG 4 WC Oncology SC Oncology GA QH518 UT WOS:A1995QH51800009 PM 7829214 ER PT J AU MCLAUGHLIN, JK LINDBLAD, P MELLEMGAARD, A MCCREDIE, M MANDEL, JS SCHLEHOFER, B POMMER, W ADAMI, HO AF MCLAUGHLIN, JK LINDBLAD, P MELLEMGAARD, A MCCREDIE, M MANDEL, JS SCHLEHOFER, B POMMER, W ADAMI, HO TI INTERNATIONAL RENAL-CELL CANCER STUDY .1. TOBACCO USE SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID RISK-FACTORS; CIGARETTE-SMOKING; ATTRIBUTABLE RISK; CARCINOMA; CONSUMPTION; COFFEE AB The relationship between renal-cell cancer (RCC) and tobacco use was investigated in an international, multicenter, population-based case-control study. Coordinated studies were conducted in Australia, Denmark, Germany, Sweden and the United States using a shared protocol and questionnaire. A total of 1,732 cases (1,050 men, 682 women) and 2,309 controls (1,429 men, 880 women) were interviewed for the study. No association was observed between risk and use of cigars, pipes or smokeless tobacco. A statistically significant association was observed for cigarette smoking, with current smokers having a 40% increase in risk [relative risk (RR)= 1.4, 95% confidence interval (CI) 1.2-1.7]. Risk increased with intensity (number of cigarettes) and duration (years smoked). Among current smokers the RR for pack-years rose from 1.1 (95% CI 0.8-1.5) for < 15.9 pack years to 2.0 (95% CI 1.6-2.7) for > 42 pack years (p for trend < 0.001). Long-term quitters (> 15 years) experienced a reduction in risk of about 15-25% relative to current smokers. Those who started smoking late (> 24 years of age) had about two-thirds the risk of those who started young (less than or equal to 12 years of age). Overall, the findings of this pooled analysis confirm that cigarette smoking is a causal factor in the etiology of RCC. (C) 1995 Wiley-Liss, Inc.(*) C1 NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. UNIV UPPSALA HOSP,CANC EPIDEMIOL UNIT,S-75185 UPPSALA,SWEDEN. DANISH CANC SOC,DANISH CANC REGISTRY,COPENHAGEN,DENMARK. NEW S WALES CANC COUNCIL,CANC EPIDEMIOL RES UNIT,KINGS CROSS,AUSTRALIA. UNIV MINNESOTA,SCH PUBL HLTH,DIV ENVIRONM HLTH,MINNEAPOLIS,MN 55455. GERMAN CANC RES CTR,DIV EPIDEMIOL,W-6900 HEIDELBERG,GERMANY. HUMBOLDT HOSP,BERLIN,GERMANY. NR 32 TC 114 Z9 115 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 17 PY 1995 VL 60 IS 2 BP 194 EP 198 DI 10.1002/ijc.2910600211 PG 5 WC Oncology SC Oncology GA QH518 UT WOS:A1995QH51800010 PM 7829215 ER PT J AU MILLER, AC SAMID, D AF MILLER, AC SAMID, D TI TUMOR RESISTANCE TO OXIDATIVE STRESS - ASSOCIATION WITH RAS ONCOGENE EXPRESSION AND REVERSAL BY LOVASTATIN, AN INHIBITOR OF P21RAS ISOPRENYLATION SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID HYDROGEN-PEROXIDE; INTRACELLULAR GLUTATHIONE; RADIATION-RESISTANCE; MAMMALIAN-CELLS; CANCER CELLS; CATALASE; GROWTH; LINES AB The ras oncogene family has been implicated in tumor resistance to ionizing radiotherapy. Using the gene-transfer model, we show here that res expression may also affect cell responses to chemical inducers of oxidative stress. Studies involving human osteosarcoma subclones, which vary in their levels of EJras expression, revealed a tight correlation between the amounts of res-encoded mRNA and p21 produced, and the degree of resistance to doxorubicin or hydrogen peroxide. Differences in response could not be explained by increased activity of anti-oxidant enzymes such as superoxide dismutase, glutathione reductase, glutathione S-transferase or glutathione peroxidase. Moreover, there were no significant differences in glutathione levels. Although the resistant cells had elevated levels of gamma-glutamyl-transferase mRNA indicative of an increased rate of glutathione turnover, this elevation was not specific for ras-transfected cell lines. Lovastatin, an inhibitor of protein isoprenylation critical for p21ras membrane association and function, restored the sensitivity of ras-transformed cells to doxorubicin and hydrogen peroxide. The data indicate that pharmacological agents affecting ras expression may enhance responses of some human tumors to free-radical-mediated chemotherapies. (C) 1995 Wiley-Liss, Inc.(*) C1 NCI,DCT,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. ARMED FORCES RADIOBIOL RES INST,DEPT RADIAT BIOCHEM,BETHESDA,MD 20889. NR 30 TC 35 Z9 36 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JAN 17 PY 1995 VL 60 IS 2 BP 249 EP 254 PG 6 WC Oncology SC Oncology GA QH518 UT WOS:A1995QH51800019 PM 7829224 ER PT J AU NATSOULIS, G SESHAIAH, P FEDERSPIEL, MJ REIN, A HUGHES, SH BOEKE, JD AF NATSOULIS, G SESHAIAH, P FEDERSPIEL, MJ REIN, A HUGHES, SH BOEKE, JD TI TARGETING OF A NUCLEASE TO MURINE LEUKEMIA-VIRUS CAPSIDS INHIBITS VIRAL MULTIPLICATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ANTIVIRALS; GENE THERAPY; STAPHYLOCOCCAL NUCLEASE ID REVERSE-TRANSCRIPTASE; RETROVIRUS VECTORS; GAG PROTEINS; READ-THROUGH; DOWNSTREAM; PSEUDOKNOT; ASSAY; CODON AB Capsid-targeted viral inactivation is an antiviral strategy in which toxic fusion proteins are targeted to virions, where they inhibit viral multiplication by destroying viral components. These fusion proteins consist of a virion structural protein moiety and an enzymatic moiety such as a nuclease. Such fusion proteins can severely inhibit transposition of yeast retrotransposon Ty1, an element whose transposition mechanistically resembles retroviral multiplication. We demonstrate that expression of a murine retrovirus capsid-staphylococcal nuclease fusion protein inhibits multiplication of the corresponding murine leukemia virus by 30- to 100-fold. Staphylococcal nuclease is apparently inactive intracellularly and hence nontoxic to the host cell, but it is active extracellularly because of its requirement for high concentrations of Ca2+ ions. Virions assembled in and shed from cells expressing the fusion protein contain very small amounts of intact viral RNA, as would be predicted for nuclease-mediated inhibition of viral multiplication. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MOLEC BIOL & GENET,BALTIMORE,MD 21205. NCI,FREDERICK CANC RES & DEV CTR,ADV BIOSCI LABS,BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101, P01-CA16519]; NIAID NIH HHS [U01-AI35282] NR 17 TC 28 Z9 35 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 17 PY 1995 VL 92 IS 2 BP 364 EP 368 DI 10.1073/pnas.92.2.364 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QC874 UT WOS:A1995QC87400006 PM 7831291 ER PT J AU LIN, YC BROWN, K SIEBENLIST, U AF LIN, YC BROWN, K SIEBENLIST, U TI ACTIVATION OF NF-KAPPA-B REQUIRES PROTEOLYSIS OF THE INHIBITOR I-KAPPA-ALPHA - SIGNAL-INDUCED PHOSPHORYLATION OF I-KAPPA-B-ALPHA ALONE DOES NOT RELEASE ACTIVE NF-KAPPA-B SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TRANSCRIPTION FACTOR; NUCLEAR TRANSLOCATION; CALPAIN INHIBITORS; PROTEASOME ID TRANSCRIPTION FACTOR; PROTEIN-KINASE; INVITRO; PATHWAY AB The transcription factor NF-kappa B is retained in the cytoplasm by its inhibitor I kappa B-alpha. Upon cellular stimulation with a variety of pathogen- or stress-related agents, I kappa B-alpha is functionally inactivated and NP-kappa B translocates to the nucleus to trigger transcription of a large array of genes, many of which encode proteins critical for immune or stress responses. Here, we demonstrate that signal-induced proteolysis of I kappa B-alpha is an obligatory Step for activation of NF-kappa B: calpain inhibitors I and II, which inhibit cysteine proteases, block activation of NF-kappa B by blocking degradation of I kappa B-alpha without affecting signal-induced phosphorylation of this inhibitor. This contrasts with previous models in which phosphorylation of I kappa B-alpha was postulated to be sufficient for activation. We demonstrate further that signal-induced phosphorylation of I kappa B-alpha does not by itself lead to dissociation of the inhibitor from NF-kappa B, providing a rationale for and confirmation of the need to proteolyze I kappa B-alpha in order to activate NF-kappa B. Signal-controlled, target-specific proteolysis is an unexpected, yet likely more general, mechanism for regulating transcription factors. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 20 TC 237 Z9 241 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 17 PY 1995 VL 92 IS 2 BP 552 EP 556 DI 10.1073/pnas.92.2.552 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA QC874 UT WOS:A1995QC87400045 PM 7831327 ER PT J AU HASELTINE, FP REDMOND, GP WENTZ, AC WILD, RA AF HASELTINE, FP REDMOND, GP WENTZ, AC WILD, RA TI PROCEEDINGS OF A SYMPOSIUM - AN NICHD CONFERENCE - ANDROGENS AND WOMENS HEALTH - INTRODUCTION SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material C1 FDN DEV ENDOCRINOL INC,BEACHWOOD,OH. UNIV OKLAHOMA,HLTH SCI CTR,DEPT OBSTET GYNECOL,OKLAHOMA CITY,OK. UNIV OKLAHOMA,HLTH SCI CTR,DIV CARDIOL,OKLAHOMA CITY,OK. RP HASELTINE, FP (reprint author), NICHHD,CTR POPULAT RES,6100 EXECUT BLVD,SUITE 8B07D,ROCKVILLE,MD 20852, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JAN 16 PY 1995 VL 98 SU 1A BP S1 EP S1 DI 10.1016/S0002-9343(99)80051-5 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA QE657 UT WOS:A1995QE65700001 ER PT J AU SAVORY, J HUANG, Y HERMAN, MM REYES, MR WILLS, MR AF SAVORY, J HUANG, Y HERMAN, MM REYES, MR WILLS, MR TI TAU-IMMUNOREACTIVITY ASSOCIATED WITH ALUMINUM MALTOLATE-INDUCED NEUROFIBRILLARY DEGENERATION IN RABBITS SO BRAIN RESEARCH LA English DT Note DE ALUMINUM; NEURODEGENERATION; TAU; RABBIT ID CENTRAL NERVOUS-SYSTEM; PATHOGENETIC IMPLICATIONS; PROTEIN IMMUNOREACTIVITY; ALZHEIMERS-DISEASE; PHOSPHORYLATION; MORPHOLOGY; DEMENTIA; FIXATION; TISSUE AB Intracisternal administration of aluminum maltolate to rabbits produces a marked argyrophilic neurofibrillary degeneration (NFD) which is also immunoreactive for both phosphorylated and non-phosphorylated microtubule associated protein tau. Using tissue fixation in PBF, the monoclonal antibodies Tau-2 and AT8 stain the NFD. Dephosphorylation markedly reduces the positivity of AT8. Using PLP-fixed tissue, monoclonal antibody Tau-1 also immunostains aluminum-induced NFD. C1 UNIV VIRGINIA,CTR HLTH SCI,DEPT PATHOL,CHARLOTTESVILLE,VA. UNIV VIRGINIA,CTR HLTH SCI,DEPT INTERNAL MED,CHARLOTTESVILLE,VA. UNIV VIRGINIA,CTR HLTH SCI,DEPT BIOCHEM,CHARLOTTESVILLE,VA. NIMH,NEUROSCI CTR ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,NEUROPATHOL SECT,WASHINGTON,DC 20032. NR 17 TC 66 Z9 66 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JAN 16 PY 1995 VL 669 IS 2 BP 325 EP 329 DI 10.1016/0006-8993(94)01297-U PG 5 WC Neurosciences SC Neurosciences & Neurology GA QC429 UT WOS:A1995QC42900022 PM 7712190 ER PT J AU SHIRANI, J YOUSEFI, J ROBERTS, WC AF SHIRANI, J YOUSEFI, J ROBERTS, WC TI MAJOR CARDIAC FINDINGS AT NECROPSY IN 366 AMERICAN OCTOGENARIANS SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID GREATER-THAN-OR-EQUAL-TO-90 YEARS; AGE; DISEASE; HEARTS; OLD AB We examined the hearts of 366 octogenarians (184 women [50%], 264 white [72%], mean age 84 +/- 4 years). The cause of death was cardiac in 195 (53%), noncardiac but vascular in 47 (13%), and noncardiac and nonvascular in 124 patients (34%). Of the 195 patients with fatal cardiac disease atherosclerotic coronary artery disease was the cause of death in 127 (65%): acute myocardial infarction in 87 (69%), sudden cardiac arrest outside the hospital in 19 (15%), chronic congestive heart failure with healed myocardial infarction in 15 (12%), and complications of coronary bypass surgery in 6 (4%). At least 1 of the 4 major (left main, left anterior descending, left circumflex, and right) epicardial coronary arteries was narrowed > 75% in cross-sectional area by atherosclerotic plaque in 218 patients (60%). The mean number of significantly narrowed major epicardial coronary arteries was 1.7, 1.3, and 0.7 in those who died of cardiac, peripheral vascular, or noncardiovascular causes, respectively. Among the 87 patients (33 men and 54 women) with fatal acute myocardial infarction, the women more often had ruptured ventricles (21 of 54 [39%] vs 3 of 33 [9%]), and fewer women had healed myocardial infarcts (11 of 54 [20%] vs 24 of 33 [73%], p < 0.05). Calcific deposits were present in the epicardial coronary arteries in 285 patients (78%), in the mitral annulus in 140 (38%), and in aortic valve cusps in 153 (42%). Most octogenarian women with fatal acute myocardial infarction had no previous nonfatal infarcts, but had a high frequency of cardiac rupture; in contrast, most men with a fatal acute myocardial infarction had had a nonfatal infarct and a low frequency of cardiac rupture. Sudden death was uncommon in both sexes in this age group. C1 NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. NR 14 TC 33 Z9 34 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 15 PY 1995 VL 75 IS 2 BP 151 EP 156 DI 10.1016/S0002-9149(00)80065-X PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA QA702 UT WOS:A1995QA70200009 PM 7810491 ER PT J AU BROOKMEYER, R QUINN, TC AF BROOKMEYER, R QUINN, TC TI ESTIMATION OF CURRENT HUMAN-IMMUNODEFICIENCY-VIRUS INCIDENCE RATES FROM A CROSS-SECTIONAL SURVEY USING EARLY DIAGNOSTIC-TESTS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE ACQUIRED IMMUNODEFICIENCY SYNDROME; CROSS-SECTIONAL STUDIES; EPIDEMIOLOGIC METHODS; HIV SEROPREVALENCE STATISTICS ID HIV-INFECTION; UNITED-STATES; TYPE-1 INFECTION; AIDS EPIDEMIC; BLOOD-DONORS; P24 ANTIGEN; ANTIBODY; TRANSMISSION; PREVALENCE; EMERGENCY AB In sharp contrast to the considerable worldwide epidemiologic data available on acquired immunodeficiency syndrome incidence and human immunodeficiency virus (HIV) seroprevalence, there is relatively little information about current levels of HIV incidence rates. The authors suggest a novel approach for estimating current HIV incidence rates based on a single cross-sectional survey and on an epidemiologic model, The approach is based on diagnostic tests for HIV p24 antigen to identify individuals in the preantibody or window period (time between exposure to HIV and appearance of detectable HIV antibodies), Individuals in the preantibody period are likely to have been infected very recently because the duration of the preantibody period is relatively short, The authors report data on the duration of p24 antigenemia prior to HIV seroconversion. This duration together with the prevalence of p24 antigenemia obtained from a cross-sectional survey are used in an epidemiologic model to estimate current incidence rates, This approach of estimating incidence rates may be especially useful in developing countries and high-risk populations in which it is difficult to follow cohorts to identify seroconverters, and in the design of vaccine efficacy studies in which current incidence rates are crucial for calculating sample sizes. C1 NIAID,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DIV INFECT DIS,BALTIMORE,MD 21205. RP BROOKMEYER, R (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT BIOSTAT,615 N WOLFE ST,BALTIMORE,MD 21205, USA. NR 34 TC 98 Z9 103 U1 0 U2 1 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 15 PY 1995 VL 141 IS 2 BP 166 EP 172 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QC463 UT WOS:A1995QC46300010 PM 7817972 ER PT J AU TILLEY, BC ALARCON, GS HEYSE, SP TRENTHAM, DE NEUNER, R KAPLAN, DA CLEGG, DO LEISEN, JCC BUCKLEY, L COOPER, SM DUNCAN, H PILLEMER, SR TUTTLEMAN, M FOWLER, SE AF TILLEY, BC ALARCON, GS HEYSE, SP TRENTHAM, DE NEUNER, R KAPLAN, DA CLEGG, DO LEISEN, JCC BUCKLEY, L COOPER, SM DUNCAN, H PILLEMER, SR TUTTLEMAN, M FOWLER, SE TI MINOCYCLINE IN RHEUMATOID-ARTHRITIS - A 48-WEEK, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE ARTHRITIS, RHEUMATOID; MINOCYCLINE; TETRACYCLINES; MYCOPLASMA INFECTIONS; COLLAGENASES ID CONTROLLED CLINICAL-TRIAL; GOLD SODIUM THIOMALATE; TETRACYCLINE; DISEASE; METHOTREXATE; AURANOFIN; SULFASALAZINE; ANTIBIOTICS; MECHANISM; CRITERIA AB Objective: To assess the safety and efficacy of minocycline in the treatment of rheumatoid arthritis. Design: A double-blind, randomized, multicenter, 48-week trial of oral minocycline (200 mg/d) or placebo. Setting: 6 clinical centers in the United States. Patients: 219 adults with active rheumatoid arthritis who had previous limited treatment with disease-modifying drugs. Measurements: As the primary outcomes, 60 diarthrodial joints were examined for tenderness, and 58 joints were examined for swelling (hips excluded). Grip strength, evaluator's global assessment, morning stiffness, Modified Health Assessment Questionnaire, patient's global assessment, hematocrit, erythrocyte sedimentation rate, platelet count, and IgM rheumatoid factor levels were also assessed; radiographs of both hands and wrists were taken. Results: 109 and 110 patients were randomly assigned to receive minocycline and placebo, respectively. At entry, demographic, clinical, and laboratory measurements were similar in both groups. Most patients had mild to moderate disease activity and some evidence of destructive disease. At the week 48 visit, 79% of the minocycline group and 78% of the placebo group continued to receive the study medication. At 48 weeks, more patients in the minocycline group than in the placebo group showed improvement in joint swelling (54% and 39%) and joint tenderness (56% and 41%) (P < 0.023 for both comparisons). The minocycline group also showed greater improvement in hematocrit, erythrocyte sedimentation rate, platelet count, and IgM rheumatoid factor levels (all P values < 0.001), and more patients receiving minocycline had laboratory values within normal ranges at 48 weeks. For the remaining outcomes, P values ranged from 0.04 to 0.76, all greater than the critical value of 0.005 (Bonferroni adjustment for multiple comparisons). The frequency of reported side effects was similar in both groups, and no serious toxicity occurred. Conclusions: Minocycline was safe and effective for patients with mild to moderate rheumatoid arthritis. Its mechanisms of action remain to be determined. C1 NIAMSD,OFF DIS PREVENT EPIDEMIOL & CLIN APPLICAT,MIRA TRIAL GRP,BETHESDA,MD 20892. HENRY FORD HLTH SCI CTR,DETROIT,MI. UNIV ALABAMA,BIRMINGHAM,AL 35294. BETH ISRAEL HOSP,DEPT RHEUMATOL,BOSTON,MA 02215. UNIV UTAH,MED CTR,DIV RHEUMATOL,SALT LAKE CITY,UT 84132. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,MCV STN,RICHMOND,VA 23298. UNIV VERMONT,CTR HLTH,BURLINGTON,VT 05401. FU NIAMS NIH HHS [N01-AR-1-2203, N01-AR-1-2205, N01-AR-1-2202] NR 52 TC 251 Z9 255 U1 1 U2 4 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 15 PY 1995 VL 122 IS 2 BP 81 EP 89 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA QC059 UT WOS:A1995QC05900001 PM 7993000 ER EF