FN Thomson Reuters Web of Science™ VR 1.0 PT J AU MCCONKEY, DJ FOSDICK, L DADAMIO, L JONDAL, M ORRENIUS, S AF MCCONKEY, DJ FOSDICK, L DADAMIO, L JONDAL, M ORRENIUS, S TI CORECEPTOR (CD4/CD8) ENGAGEMENT ENHANCES CD3-INDUCED APOPTOSIS IN THYMOCYTES IMPLICATIONS FOR NEGATIVE SELECTION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL RECEPTOR; PROTEIN-TYROSINE KINASE; IMMATURE THYMOCYTES; ZETA-CHAIN; POSITIVE SELECTION; SURFACE MOLECULES; ANTIGEN RECEPTOR; CLONAL DELETION; LYMPHOCYTES-T; CD4 AB Negative selection of self-reactive immature T cells is mediated by TCR engagement and is thought to occur via apoptosis (programmed cell death). The requirement for the co-receptors CD4 and CD8 in negative selection has been demonstrated, but the biochemical mechanisms underlying their involvement in this process remain undefined. Here we present evidence that co-receptor engagement dramatically enhances CD3-induced endonuclease activation and cell death characteristic of apoptosis in immature thymocytes. The responses are associated with increased tyrosine phosphorylation of a number of cellular substrates, including the gamma isoform of phospholipase C, and with increased association of tyrosine phosphoproteins, including the protein tyrosine kinase p56(lck), with the TCR complex. Co-receptor engagement also potentiated CD3-mediated Ca2+ increases via a mechanism dependent upon tyrosine kinase activation. Sustained Ca2+ availability was found to be necessary for endonuclease activation and apoptosis to occur. We suggest that CD4 and CD8 may participate in negative selection by enhancing TCR/CD3-induced tyrosine kinase activation and sustained Ca2+ increases that lead to endonuclease activation and apoptosis in self-reactive CD4(+)CD8(+) thymocytes. C1 NIAID,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20891. KAROLINSKA INST,STOCKHOLM,SWEDEN. RP MCCONKEY, DJ (reprint author), UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT CELL BIOL,BOX 173,1515 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. FU NCI NIH HHS [CA16672] NR 45 TC 20 Z9 20 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1994 VL 153 IS 6 BP 2436 EP 2443 PG 8 WC Immunology SC Immunology GA PF189 UT WOS:A1994PF18900008 PM 8077659 ER PT J AU SPRENGER, H LLOYD, AR MEYER, RG JOHNSTON, JA KELVIN, DJ AF SPRENGER, H LLOYD, AR MEYER, RG JOHNSTON, JA KELVIN, DJ TI GENOMIC STRUCTURE, CHARACTERIZATION, AND IDENTIFICATION OF THE PROMOTER OF THE HUMAN IL-8 RECEPTOR-A GENE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN INTERLEUKIN-8 RECEPTOR; NEUTROPHIL-ACTIVATING PEPTIDE-2; FUNCTIONAL EXPRESSION; BETA-2-ADRENERGIC RECEPTOR; MOLECULAR-CLONING; BINDING-PROTEIN; AMINO TERMINUS; HIGH-AFFINITY; TATA-BOX; TRANSCRIPTION AB Two unique but homologous receptors for the neutrophil chemoattractant, IL-8 have been cloned (designated IL-8RA and IL-8RB), each of which binds IL-8 with high affinity. IL-8RA mRNA expression was found to be regulated by granulocyte-CSF and LPS. in an attempt to understand the tissue-specific expression and to identify transcriptional regulatory elements, we have cloned, sequenced, and characterized the human IL-8RA gene. A h-DASH clone encoding the entire human IL-8RA gene was isolated by screening a genomic library with a PCR-generated cDNA. After mapping, subcloning, and sequencing several restriction fragments, a 9.2-kb continuous DNA sequence was obtained. As the sizes of the published cDNA (1.9 kb) and the mRNA determined by Northern blot analysis (2.1 kb) were not in agreement, a full-length cDNA was cloned by using a modified rapid amplification of cDNA ends technique. We identified a 5'-untranslated region of 119 bp. After comparison with the genomic sequence, we found the gene consisted of two exons interrupted by an intron of 1.7 kb. A 1050-bp ORF was encoded entirely in the second exon together with a 834-bp 3'-untranslated region. The immediate GC-rich 5'-flanking region upstream of exon 1 could serve as a constitutively active promoter in chloramphenicol-acetyl-transferase-expression assays. Expression analysis of additional upstream regions suggested the presence of silencer elements between positions -841 and -280. In conclusion, cloning a full-length cDNA permitted us to clone the human IL-8RA gene, identify the genomic structure, and characterize the promoter region. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NR 45 TC 32 Z9 32 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 SEP 15 PY 1994 VL 153 IS 6 BP 2524 EP 2532 PG 9 WC Immunology SC Immunology GA PF189 UT WOS:A1994PF18900017 PM 8077663 ER PT J AU GAZZINELLI, RT WYSOCKA, M HAYASHI, S DENKERS, EY HIENY, S CASPAR, P TRINCHIERI, G SHER, A AF GAZZINELLI, RT WYSOCKA, M HAYASHI, S DENKERS, EY HIENY, S CASPAR, P TRINCHIERI, G SHER, A TI PARASITE-INDUCED IL-12 STIMULATES EARLY IFN-GAMMA SYNTHESIS AND RESISTANCE DURING ACUTE INFECTION WITH TOXOPLASMA-GONDII SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; TUMOR-NECROSIS-FACTOR; CD8+ LYMPHOCYTES-T; INTERFERON-GAMMA; FACTOR-ALPHA; INTERLEUKIN-12; CD4+; MICE; INDUCTION; IMMUNODEFICIENCY AB In vitro and in vivo studies were performed to assess the involvement of IL-12 in resistance to acute and chronic infection with an avirulent strain of Toxoplasma gondii. Our previous findings implicated macrophages as a major source of parasite-induced IL-12. This finding was confirmed by showing that peritoneal macrophages exposed to either live parasites or soluble tachyzoite Ags produce IL-12 protein. In mice, increased expression of IL-12 (p40) mRNA in both spleen and peritoneal cells was detected as early as 2 days postinfection. Treatment with neutralizing mAbs against IL-12 increased the susceptibility of C57BL/6, BALB/c, and severe combined immunodeficient (SCID) mice to acute infection, which resulted in 100% mortality within the first 15 days after parasite inoculation. In contrast, neutralization of endogenously produced IL-12 had no effect when given during chronic infection. In agreement with the survival data, treatment with anti-IL-12 resulted in decreased IFN-gamma and enhanced Th2 (IL-4 and IL-10) cytokine synthesis by splenocytes when given during acute, but not chronic, toxoplasmosis. Sorting experiments on spleen cells from acutely infected mice indicated that both CD4(+) lymphocytes and NK1.1(+)/CD3(-) cells contribute to the early IFN-gamma response. In contrast, CD4(+) cells were found to be the major source of the cytokine during chronic disease. Together, these results suggest that the stimulation of macrophage-derived IL-12 plays a major role in both the induction of resistance and Th1 cell subset selection in acute T. gondii infection, but may not be required to maintain established immunity. C1 NEI,IMMUNOL LAB,BETHESDA,MD 20892. WISTAR INST ANAT & BIOL,HUMAN IMMUNOL LAB,PHILADELPHIA,PA 19104. RP GAZZINELLI, RT (reprint author), NIAID,PARASIT DIS LAB,IMMUNOL & CELL BIOL SECT,9000 ROCKVILLE PIKE,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 35 TC 524 Z9 532 U1 1 U2 9 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1994 VL 153 IS 6 BP 2533 EP 2543 PG 11 WC Immunology SC Immunology GA PF189 UT WOS:A1994PF18900018 PM 7915739 ER PT J AU HUI, GSN GOSNELL, WL CASE, SE HASHIRO, C NIKAIDO, C HASHIMOTO, A KASLOW, DC AF HUI, GSN GOSNELL, WL CASE, SE HASHIRO, C NIKAIDO, C HASHIMOTO, A KASLOW, DC TI IMMUNOGENICITY OF THE C-TERMINAL 19KDA FRAGMENT OF THE PLASMODIUM-FALCIPARUM - MEROZOITE SURFACE PROTEIN-1 (MSP1), YMSP119 EXPRESSED IN SACCHAROMYCES-CEREVISIAE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; IMMUNE-RESPONSE; LIPID-A; T-CELLS; ANTIGEN; GP195; PRECURSOR; GROWTH; BACULOVIRUS; ADJUVANTS AB The immunogenicity of the C-terminal 19-kDa fragment of Plasmodium falciparum MSPI expressed in yeast as a nonfusion product, YMSP1(19), was studied. Immunization with YMSP1(19) in rabbits induced high titers of Abs specific for native conformational epitopes on parasite MSP1. In mice, immunogenicity was dependent on the mouse strain and the adjuvant formulation. This suggests that different adjuvants may alter the immunogenicity of MSP1(19) in a genetically diverse population. Although YMSP1(19) induced anti-MSP1 Abs, they did not inhibit in vitro parasite growth. This contrasts with the strong inhibitory activities of Abs produced against a recombinant MSP1(42) (BVp42), which contains the entire MSP1(19) coding sequence. Further analyses showed that YMSP1(19) was the target of the inhibitory, anti-BVp42 Abs because YMSP1(19) could completely block binding of anti-BVp42 Abs to parasite MSP1 or BVp42. Moreover, depletion of YMSP1(19)-specific Abs completely abolished the parasite inhibitory activities of anti-BVp42 sera. Anti-YMSP1(19) sera did not block the inhibitory activities of anti-BVp42 sera, suggesting that inhibitory epitopes were not in close structural proximity with noninhibitory epitopes. The finding that YMSP1(19) possessed inhibitory epitopes but induced anti-MSP1 Abs that were not inhibitory suggests that although the T-epitope(s) produced by immunization with YMSP1(19) could provide help for Ab production, it did not induce an effective inhibitory Ab response. We hypothesize that the nature/specificity of T helper epitopes on MSP1 may be crucial in efficient induction of biologically relevant and/or protective Abs. C1 UNIV HAWAII,DEPT TROP MED,HONOLULU,HI 96816. NIH,MALARIA RES LAB,MOLEC VACCINE SECT,BETHESDA,MD. FU NIAID NIH HHS [AI30589] NR 30 TC 29 Z9 30 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1994 VL 153 IS 6 BP 2544 EP 2553 PG 10 WC Immunology SC Immunology GA PF189 UT WOS:A1994PF18900019 PM 8077664 ER PT J AU BAUMGARTNER, RA YAMADA, K DERAMO, VA BEAVEN, MA AF BAUMGARTNER, RA YAMADA, K DERAMO, VA BEAVEN, MA TI SECRETION OF TNF FROM A RAT MAST-CELL LINE IS A BREFELDIN A-SENSITIVE AND A CALCIUM/PROTEIN KINASE C-REGULATED PROCESS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; FC-EPSILON-RI; BASOPHILIC LEUKEMIA-CELLS; RBL-2H3 CELLS; TYROSINE PHOSPHORYLATION; 2H3 CELLS; HISTAMINE-RELEASE; MESSENGER-RNA; INOSITOL 1,4,5-TRISPHOSPHATE; MULTIFUNCTIONAL CYTOKINES AB Stimulated mast cells and cognate cultured cell lines produce and secrete a variety of cytokines including TNF. Because the mechanism by which cytokines are delivered to the external milieu is unknown, the release of TNF was studied in a rat mast cell line (RBL-2H3 cells). In these cells, TNF was not constitutively expressed nor incorporated into secretory granules but was generated de novo upon cell stimulation. It was then released by a process analogous to constitutive secretion in that brefeldin A, an agent known to disrupt Golgi membranes in these cells, inhibited this release without inhibiting release of secretory granules. Unlike constitutive secretion, however, the secretion of TNF was highly regulated by Ca2+ and protein kinase C. Studies with various stimulants and inhibitors indicated that simultaneous mobilization of Ca2+ and activation of protein kinase C were sufficient signals for secretion although optimal production of TNF may be dependent on additional synergistic signals. Because suppression of Ca2+ mobilization or inhibition of protein kinase C alone abrogated TNF secretion, the process may be amenable to therapeutic intervention. RP BAUMGARTNER, RA (reprint author), NHLBI,CHEM PHARMACOL LAB,ROOM 8N108,BLDG 10,BETHESDA,MD 20892, USA. NR 51 TC 80 Z9 80 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1994 VL 153 IS 6 BP 2609 EP 2617 PG 9 WC Immunology SC Immunology GA PF189 UT WOS:A1994PF18900026 PM 8077671 ER PT J AU CHARY, KVR KHAN, KK RASTOGI, VK GOVIL, G HOWARD, FB MILES, HT AF CHARY, KVR KHAN, KK RASTOGI, VK GOVIL, G HOWARD, FB MILES, HT TI SEQUENCE EFFECTS ON DNA STEREODYNAMICS - CONFORMATIONAL BEHAVIOR OF D-GGTAGIACTACC CONTAINING IA MISMATCHED BASE-PAIRS SO JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; DIMENSIONAL NMR-SPECTROSCOPY; G.A MISMATCH; DUPLEX; DEOXYINOSINE; DECAMER; HAIRPIN; OLIGONUCLEOTIDES; IDENTIFICATION; MACROMOLECULES AB An oligonucleotide d-GGTAGIACTACC (GC58) containing tandem inosine-adenosine (IA) mismatched base pairs has been studied by H-1 and P-31 NMR spectroscopy. Unique assignments of H-1 and P-31 spins have been achieved by 2D HELCO technique. The NOESY spectrum in 90% H2O + 10% (H2O)-H-2 has been used to assign all the exchangeable protons. NMR results indicate that at concentrationse above 2.5 mM, the molecule adopts a duplex structure. Cross-strand nOes between the 1NH proton of 16 and H2 proton of A7 and that between H2 of 16 and H2 of A7 provide evidence for IA base pairing, with both bases in anti conformation. The observed nOe connectivities d(1), d(2), and d(3) all the way from C12 to A7 and from T3 to G1 are consistent with a right-handed B-DNA conformation. However, the molecule adopts a more extended conformation in the mismatch region to accommodate the bulky IA base pairs. NMR experiments at lower concentrations indicate the coexistence of a monomeric structure in equilibrium with the duplex. 2D ROESY experiments at 1 mM concentration show that the conformation at the ends of the monomer does not deviate much from the corresponding region of the duplex, but the nucleotides in the central region undergo significant structural changes. The stereodynamics of GC58 differs significantly from an analogous dodecamer d-GGTACIAGTACC (CG58). A subtle change caused by the transposition of bases flanking the IA mismatch pairs provides greater stability both to the duplex and to the monomer in case of CG58. C1 TATA INST FUNDAMENTAL RES,CHEM PHYS GRP,BOMBAY 400005,INDIA. NIDDKD,BETHESDA,MD 20892. NR 36 TC 5 Z9 5 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3654 J9 J PHYS CHEM-US JI J. Phys. Chem. PD SEP 15 PY 1994 VL 98 IS 37 BP 9119 EP 9125 DI 10.1021/j100088a005 PG 7 WC Chemistry, Physical SC Chemistry GA PH087 UT WOS:A1994PH08700006 ER PT J AU FREY, CM FEUER, EJ TIMMEL, MJ AF FREY, CM FEUER, EJ TIMMEL, MJ TI PROJECTION OF INCIDENCE RATES TO A LARGER POPULATION USING ECOLOGIC VARIABLES SO STATISTICS IN MEDICINE LA English DT Article ID CANCER MORTALITY-RATES; POISSON REGRESSION; MODELS; OVERDISPERSION; INCOME; TESTS AB There is wide acceptance of direct standardization of vital rates to adjust for differing age distributions according to the representation within age categories of some referent population. One can use a similar process to standardize, and subsequently project vital rates with respect to continuous, or ratio scale ecologic variables. We obtained from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) programme, a 10 per cent subset of the total U.S. population, country-level breast cancer incidence during 1987-1989 for white women aged 50 and over. We applied regression coefficients that relate ecologic factors to SEER incidence to the full national complement of county-level information to produce an age and ecologic factor adjusted rate that may be more representative of the U.S. than the simple age-adjusted SEER incidence. We conducted a validation study using breast cancer mortality data available for the entire U.S. and which supports the appropriateness of this method for projecting rates. C1 NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD 20904. RP FREY, CM (reprint author), GEISINGER MED CTR,100 N ACAD AVE,DANVILLE,PA 17822, USA. NR 22 TC 8 Z9 8 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD SEP 15 PY 1994 VL 13 IS 17 BP 1755 EP 1770 DI 10.1002/sim.4780131707 PG 16 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA PH158 UT WOS:A1994PH15800006 PM 7997709 ER PT J AU MUKHOPADHYAY, AK BOSE, S HENDLER, RW AF MUKHOPADHYAY, AK BOSE, S HENDLER, RW TI MEMBRANE-MEDIATED CONTROL OF THE BACTERIORHODOPSIN PHOTOCYCLE SO BIOCHEMISTRY LA English DT Article ID PURPLE MEMBRANE; DELIPIDATION AB The ability of actinic light to modify the proportion of fast and slow forms of the M intermediate (i.e., M(f) and M(s)) in the bacteriorhodopsin (BR) photocycle is lost by exposure of the purple membrane (PM) to 0.05% Triton for 1-2 min, The decay path of Mf through the O intermediate is also lost, and new, much slower kinetic forms of M appear. In this brief exposure, the trimer structure for BR, as measured by circular dichroism (CD) exciton coupling and sedimentability, is unaffected. The optical properties of the treated PM are affected within seconds of exposure to the detergent as indicated by an increase in transmittance and a blue shift in the wavelength of maximum absorbance for the ground state. Different concentrations of Triton cause reproducibly different changes in the kinetics of the system. These observations support the view that the BR trimer-membrane interaction is important in controlling the BR photocycle. C1 NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. NR 19 TC 31 Z9 31 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 13 PY 1994 VL 33 IS 36 BP 10889 EP 10895 DI 10.1021/bi00202a007 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PG021 UT WOS:A1994PG02100007 PM 8086405 ER PT J AU OCONNELL, TM GABEL, SA LONDON, RE AF OCONNELL, TM GABEL, SA LONDON, RE TI ANOMERIC DEPENDENCE OF FLUORODEOXYGLUCOSE TRANSPORT IN HUMAN ERYTHROCYTES SO BIOCHEMISTRY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; HUMAN RED-CELL; GLUCOSE TRANSPORTER; SELECTIVE INVERSION; INVIVO METABOLISM; NMR-SPECTROSCOPY; CHEMICAL-SHIFTS; SPIN TRANSFER; RAT-BRAIN; C-13 NMR AB The transport of several n-fluoro-n-deoxy-D-glucose derivatives across the human erythrocyte membrane has been studied under equilibrium exchange conditions using one- and two-dimensional nuclear magnetic resonance (NMR) techniques. This approach is based on the intracellular F-19 shift, which was found to depend on the anomeric form and on the F/OH substitution position. Since the transport behavior of both glucose anomers can be followed simultaneously, this approach is particularly sensitive to differences in anomeric permeability. For 2-, 3-, 4-, and 6-fluorodeoxyglucose analogs, the at anomers permeate more rapidly, and the P-alpha/P-beta ratio is dependent on the position of fluorination, with values of 1.1, 1.3, 2.5, and 1.6, respectively, obtained at 37 degrees C. These results have been analyzed in terms of a simple alternating conformation model for the glucose transporter. Although mutarotase activity has been reported for red cells, mutarotation behavior for all anomers was found to be completely negligible on the transport and spin-lattice relaxation time scales. Metabolic transformation of the fluorinated glucose analogs, primarily to fluorinated gluconate and sorbitol analogs, is very slow and does not significantly interfere with the transport measurements. A mean ratio of 2.6 was found for the extracellular/intracellular fluorine spin-lattice relaxation rates. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. NR 45 TC 9 Z9 9 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 13 PY 1994 VL 33 IS 36 BP 10985 EP 10992 DI 10.1021/bi00202a018 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PG021 UT WOS:A1994PG02100018 PM 8086416 ER PT J AU SHAHABUDDIN, M RAWLINGS, DJ KASLOW, DC AF SHAHABUDDIN, M RAWLINGS, DJ KASLOW, DC TI A NOVEL GLUCOSE-6-PHOSPHATE-DEHYDROGENASE IN PLASMODIUM-FALCIPARUM - CDNA AND PRIMARY-PROTEIN STRUCTURE SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Note DE MALARIA; CLONING; HEXOSE MONOPHOSPHATE SHUNT; POLYMERASE CHAIN REACTION ID SACCHAROMYCES-CEREVISIAE; ENCODING GLUCOSE-6-PHOSPHATE-DEHYDROGENASE; SEQUENCE-ANALYSIS; GENE; IDENTIFICATION; INACTIVATION; ADAPTATION; CLONING; PATHWAY; ENZYME AB The structure of the parasite-encoded G6PD (PfG6PD) may provide clues about the relative protection against malaria in humans with glucose-6-phosphate dehydrogenase (G6PD) deficiency. We have cloned Pfg6pd cDNA encoding a predicted 856 amino acid residues polypeptide with a calculated molecular mass of > 94 kDa. The predicted amino acid sequence is highly homologous to G6PD from other organisms. Pfg6pd maps as a single or low copy number gene to chromosome 14. The unusually large N-terminus and the distance between the NADP-binding site and G6PD-binding site is novel for the parasite G6PD. The differences between parasite and human G6PD proteins could potentially be exploited for designing new chemotherapeutic agents. C1 NIAID,MOLEC VACCINE SECT,MALARIA RES LAB,BETHESDA,MD 20892. NR 24 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD SEP 13 PY 1994 VL 1219 IS 1 BP 191 EP 194 DI 10.1016/0167-4781(94)90269-0 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PG999 UT WOS:A1994PG99900030 PM 8086463 ER PT J AU PARK, KC KIM, SJ BANG, YJ PARK, JG KIM, NK ROBERTS, AB SPORN, MB AF PARK, KC KIM, SJ BANG, YJ PARK, JG KIM, NK ROBERTS, AB SPORN, MB TI GENETIC CHANGES IN THE TRANSFORMING GROWTH-FACTOR-BETA (TGF-BETA) TYPE-II RECEPTOR GENE IN HUMAN GASTRIC-CANCER CELLS - CORRELATION WITH SENSITIVITY TO GROWTH-INHIBITION BY TGF-BETA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EXPRESSION CLONING; CARCINOMA; LINES; CARCINOGENESIS; BETAGLYCAN; RESPONSES; COMPLEX; KINASE AB We have found several genetic changes in the TGF-beta type II receptor gene in human gastric cancer cell lines resistant to the growth inhibitory effect of TGF-beta. Southern blot analysis showed deletion of the type II receptor gene in two of eight cell lines and amplification in another two lines. The single cell line we studied that is sensitive to growth inhibition by TGF-beta showed no structural abnormalities of the type II receptor gene. Some of the gastric cancer cells resistant to the growth inhibitory effect of TGF-beta express either truncated or no detectable TGF-beta type II receptor mRNAs, whereas the one that retains responsiveness to the growth inhibitory effect of TGF-beta expresses a full-size type II receptor mRNA. Immuno-precipitation followed by Western blot analysis showed parallel changes in TGF-beta type II receptor expression. Our results suggest that one of the possible mechanisms of escape from autocrine or paracrine growth control by TGF-beta during carcinogenesis could involve genetic changes in the TGF-beta type II receptor gene itself or altered expression of its mRNA. C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. SEOUL NATL UNIV HOSP,COLL MED,DEPT INTERNAL MED,SEOUL 110744,SOUTH KOREA. SEOUL NATL UNIV HOSP,COLL MED,DEPT SURG,SEOUL 110744,SOUTH KOREA. RI Park, Jae-Gahb/J-5494-2012; Bang, Yung Jue/J-2759-2012 NR 34 TC 404 Z9 420 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 13 PY 1994 VL 91 IS 19 BP 8772 EP 8776 DI 10.1073/pnas.91.19.8772 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PG521 UT WOS:A1994PG52100009 PM 8090721 ER PT J AU PEPE, S BOGDANOV, K HALLAQ, H SPURGEON, H LEAF, A LAKATTA, E AF PEPE, S BOGDANOV, K HALLAQ, H SPURGEON, H LEAF, A LAKATTA, E TI OMEGA-3 POLYUNSATURATED FATTY-ACID MODULATES DIHYDROPYRIDINE EFFECTS ON L-TYPE CA2+ CHANNELS, CYTOSOLIC CA2+, AND CONTRACTION IN ADULT-RAT CARDIAC MYOCYTES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PATCH CLAMP RECORDING; INDO-1 FLUORESCENCE ID CALCIUM CHANNELS; ARACHIDONIC-ACID AB The effect of docosahexaenoic acid (DHA; C22:6) on dihydropyridine (DHP) interaction with L-type Ca2+ channel current (I-Ca), cytosolic Ca2+ (Ca-i), and cell contraction in isolated adult rat cardiac myocytes was studied. The DHP L-type Ca2+-channel blocker nitrendipine (10 nM) reduced peak I-Ca (measured by whole-cell voltage clamp from -45 to 0 mV) and reduced the amplitude of the Ca2+ transient (measured as the transient in indo-1 fluorescence, 410/490 nm) and the twitch amplitude (measured via photodiode array) during steady-state electrical stimulation (0.5 Hz). The DHP L-type Ca2+ channel agonist BAY K 8644 (10 nM) significantly increased I-Ca, the amplitude of the Ca-i transient, and contraction. When cells were exposed to DHA (5 mu M) simultaneously with either BAY K 8644 or nitrendipine, the drug effects were abolished. Arachidonic acid (C20:4) at 5 mu M did not block the inhibitory effects of nitrendipine nor did it prevent the potentiating effects of BAY K 8644. DHA modulation of DHP action could be reversed by cell perfusion with fatty acid-free bovine serum albumin at 1 mg/ml. Neither DHA nor arachidonic acid alone (5 mu M) had any apparent effect on the parameters measured. DHA (5 mu M) had no influence over beta-adrenergic receptor stimulation (isoproterenol, 0.01-1 mu M)-induced increases in I-Ca, Ca-i, or contraction. The findings that DHA inhibits the effect of DHP agonists and antagonists on Ca2+-channel current but has no effect alone or on beta-adrenergic-induced increases in I-Ca suggests that DHA specifically binds to Ca2+ channels at or near DHP binding sites and interferes with I-Ca modulation. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. BROCKTON W ROXBURY VET AFFAIRS MED CTR,BOSTON,MA 02132. FU NIDDK NIH HHS [DK38165] NR 14 TC 100 Z9 101 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 13 PY 1994 VL 91 IS 19 BP 8832 EP 8836 DI 10.1073/pnas.91.19.8832 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PG521 UT WOS:A1994PG52100021 PM 7522322 ER PT J AU SAKAMOTO, H LEWIS, MS KODAMA, H APPELLA, E SAKAGUCHI, K AF SAKAMOTO, H LEWIS, MS KODAMA, H APPELLA, E SAKAGUCHI, K TI SPECIFIC SEQUENCES FROM THE CARBOXYL-TERMINUS OF HUMAN P53 GENE-PRODUCT FORM ANTI-PARALLEL TETRAMERS IN SOLUTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE OLIGOMERIZATION; COILED-COIL; 4-HELICAL BUNDLE; TUMOR-SUPPRESSOR GENE ID DNA-BINDING DOMAIN; S-ALKYL THIOESTER; LEUCINE-ZIPPER; PROTEIN; PEPTIDE; MUTATIONS; OLIGOMERIZATION; TRANSFORMATION; MUTANTS; ACID AB Human p53 is a tumor-suppressor gene product associated with control of the cell cycle and with growth suppression, and it is known to form homotetramers in solution. To investigate the relationship of structure to tetramerization, nine peptides corresponding to carboxyl-terminal sequences in human p53 were chemically synthesized, and their equilibrium associative properties were determined by analytical ultracentrifugation. Secondary structure, as determined by circular dichroism measurements, was correlated with oligomerization properties of each peptide. The sedimentation profiles of peptides 319-393 and 319-360 fit a two-state model of peptide monomers in equilibrium with peptide tetramers. Successive deletion of amino and carboxyl-terminal residues from 319-360 reduced tetramer formation. Further, substitution of alanine for Leu-323, Tyr-327, and Leu-330 abolished tetramerization. Circular dichroism studies showed that peptide 319-351 had the highest alpha-helix content, while the other peptides that did not form tetramers had low helical structure. These studies define a minimal region and identify certain critical residues involved in tetramerization. Cross-linking studies between monomer units in the tetramer suggest that the helices adopt an anti-parallel arrangement. We propose that conformational shifts in the helical structure of the p53 tetramerization domain result in a repositioning of subunits relative to one another. This repositioning provides an explanation relating conformational changes at the carboxyl terminus with changes in sequence specific DNA binding by the highly conserved central domain. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. SAGA UNIV,FAC SCI & ENGN,BIOCHEM LAB,SAGA 840,JAPAN. RI Sakamoto, Hiroshi/A-3181-2011 NR 23 TC 64 Z9 69 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 SEP 13 PY 1994 VL 91 IS 19 BP 8974 EP 8978 DI 10.1073/pnas.91.19.8974 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PG521 UT WOS:A1994PG52100050 PM 8090755 ER PT J AU DIGIOVANNI, SR NIELSEN, S CHRISTENSEN, EI KNEPPER, MA AF DIGIOVANNI, SR NIELSEN, S CHRISTENSEN, EI KNEPPER, MA TI REGULATION OF COLLECTING DUCT WATER CHANNEL EXPRESSION BY VASOPRESSIN IN BRATTLEBORO RAT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PURIFICATION; ACTIVATION; PROTEIN; TUBULES; BINDING; KIDNEY; IMCD AB AQP-CD is a vasopressin regulated water channel expressed exclusively in the renal collecting duct. We have previously shown that AQP-CD is present in the apical plasma membrane and subapical vesicles of collecting duct cells, consistent with membrane-shuttling mechanisms that have been proposed to explain the short-term action of [Arg(8)]vasopressin (AVP) to regulate apical water permeability. We propose here that AVP may also have long-term actions on the collecting duct to regulate the expression of the AQP-CD water channel. We used immunoblotting, immunohistochemistry, and in vitro perfusion of renal tubules to investigate water channel regulation in collecting ducts of diabetes insipidus (Brattleboro) rats treated with a 5-day infusion of AVP or vehicle. Immunoblotting and immunohistochemistry demonstrated that collecting ducts of vehicle-infused Brattleboro rats had markedly reduced expression of AQP-CD relative to normal rats. In response to AVP infusion there was a nearly 3-fold increase in AQP-CD expression as detected by immunoblotting. Immunocytochemistry demonstrated that the increased expression was predominantly in the apical plasma membrane and subapical vesicles of collecting duct cells. Inner medullary collecting ducts of AVP-infused Brattleboro rats displayed a 3-fold increase in osmotic water permeability relative to vehicle-infused controls, in parallel with the change in AQP-CD expression. Based on these findings, we conclude that (i) long-term infusion of AVP, acting either directly or indirectly, regulates expression of the AQP-CD water channel and (ii) AQP-CD is the predominant AVP-regulated water channel. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. AARHUS UNIV,DEPT CELL BIOL,DK-8000 AARHUS C,DENMARK. NR 24 TC 334 Z9 340 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 13 PY 1994 VL 91 IS 19 BP 8984 EP 8988 DI 10.1073/pnas.91.19.8984 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PG521 UT WOS:A1994PG52100052 PM 7522327 ER PT J AU SU, YA TRENT, JM GUAN, XY MELTZER, PS AF SU, YA TRENT, JM GUAN, XY MELTZER, PS TI DIRECT ISOLATION OF GENES ENCODED WITHIN A HOMOGENEOUSLY STAINING REGION BY CHROMOSOME MICRODISSECTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRANSCRIBED SEQUENCES; HUMAN SARCOMAS; MALIGNANT-MELANOMA; RAPID GENERATION; AMPLIFIED DNA; AMPLIFICATION; SELECTION; IDENTIFICATION; PROTEIN; PROBES AB Identification of genes involved in recurring chromosome rearrangements has provided significant insight into the molecular basis of malignancy. We describe here a strategy combining chromosome microdissection and hybrid selection for the direct isolation of chromosome region-specific genes. We modeled this strategy by using sequences recovered from the microdissection of a homogeneously staining region to allow isolation of genes that were overexpressed and present at high copy number within the homogeneously staining region, including the direct isolation of two genes encoded within a 12q homogeneously staining region found in the osteosarcoma cell line OsA-CL. Although first applied to amplified genes, this strategy should be applicable to the isolation of cDNAs from any chromosomal region. C1 NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892. RI Guan, Xin-Yuan/A-3639-2009 OI Guan, Xin-Yuan/0000-0002-4485-6017 FU NCI NIH HHS [CA-29476, CA-56725]; NHGRI NIH HHS [P30-HG-00209] NR 36 TC 37 Z9 38 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 13 PY 1994 VL 91 IS 19 BP 9121 EP 9125 DI 10.1073/pnas.91.19.9121 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PG521 UT WOS:A1994PG52100080 PM 8090779 ER PT J AU PIMENTA, PFP SARAIVA, EMB ROWTON, E MODI, GB GARRAWAY, LA BEVERLEY, SM TURCO, SJ SACKS, DL AF PIMENTA, PFP SARAIVA, EMB ROWTON, E MODI, GB GARRAWAY, LA BEVERLEY, SM TURCO, SJ SACKS, DL TI EVIDENCE THAT THE VECTORIAL COMPETENCE OF PHLEBOTOMINE SAND FLIES FOR DIFFERENT SPECIES OF LEISHMANIA IS CONTROLLED BY STRUCTURAL POLYMORPHISMS IN THE SURFACE LIPOPHOSPHOGLYCAN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DONOVANI LIPOPHOSPHOGLYCAN; GLYCOCONJUGATE; PAPATASI; MIDGUT AB Phlebotomine vectors can in some instances transmit only certain species of Leishmania. Comparison of a large number of vector/parasite pairs revealed that species-specific differences in vectorial competence were in every case directly correlated with the ability of promastigotes to attach to the sand-fly midgut, the variable outcomes of which were controlled by structural polymorphisms in the surface lipophosphoglycan (LPG) of the parasite. The ability of Phlebotomus papatasi to transmit only Leishmania major could be attributed to the unique, highly substituted nature of L. major LPG that provides for multiple terminally exposed beta-linked galactose residues for binding. While the relatively unsubstituted LPGs of other Leishmania species were unable to mediate promastigote attachment to P. papatasi, they could mediate binding to midguts of Phlebotomus argentipes, which was found to be a potentially competent vector for every Leishmania species examined. The data suggest that at least some phlebotomine vectors differ with respect to the parasite recognition sites which they express and that midgut adhesion is a sufficiently critical component of vectorial competence as to provide the evolutionary drive for LPG structural polymorphisms. C1 NIAID,IMMUNOL & CELL BIOL SECT,PARASIT DIS LAB,BETHESDA,MD 20892. WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,DEPT ENTOMOL,WASHINGTON,DC 20307. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. UNIV KENTUCKY,MED CTR,DEPT BIOCHEM,LEXINGTON,KY 40536. RI Rowton, Edgar/A-4474-2012; Rowton, Edgar/A-1975-2011; OI Rowton, Edgar/0000-0002-1979-1485; Beverley, Stephen/0000-0001-5319-0811 FU NIAID NIH HHS [AI2964] NR 27 TC 134 Z9 137 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 13 PY 1994 VL 91 IS 19 BP 9155 EP 9159 DI 10.1073/pnas.91.19.9155 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PG521 UT WOS:A1994PG52100087 PM 8090785 ER PT J AU SONG, ZH YOUNG, WS BROWNSTEIN, JM BONNER, TI AF SONG, ZH YOUNG, WS BROWNSTEIN, JM BONNER, TI TI MOLECULAR-CLONING OF A NOVEL CANDIDATE G-PROTEIN-COUPLED RECEPTOR FROM RAT-BRAIN SO FEBS LETTERS LA English DT Article DE G PROTEIN-COUPLED RECEPTOR; CLONING; RAT BRAIN; STRIATUM; RETROSPLENIAL CORTEX ID NEUROPEPTIDE RECEPTOR; HORMONE RECEPTOR; MAMMALIAN-CELLS; EXPRESSION; FAMILY; ENCODES; NEURONS; SYSTEM AB A PCR cloning strategy using primers designed from sequences selectively conserved among a cannabinoid receptor and two orphan receptors, was used to isolate novel G protein-coupled receptors. rCNL3, a 1.75 kb cDNA encoding a 363 amino acid protein, was isolated from a rat cerebral cortex library. Sequence analysis showed that rCNL3 possesses a number of structural characteristics of G protein-coupled receptors and has 61% amino acid identity (from transmembrane region one through the carboxyl-terminus) with two other candidate G protein-coupled receptors. Therefore, these three receptors may comprise a receptor subfamily with identical or closely related endogenous ligands. Northern and in situ hybridization experiments demonstrated that rCNL3 mRNA is expressed in the rat brain, with a prominent distribution in striatum. RP SONG, ZH (reprint author), NIMH,CELL BIOL LAB,BLDG 36,ROOM 3 A17,BETHESDA,MD 20892, USA. RI Young, W Scott/A-9333-2009; Brownstein, Michael/B-8609-2009 OI Young, W Scott/0000-0001-6614-5112; NR 25 TC 13 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD SEP 12 PY 1994 VL 351 IS 3 BP 375 EP 379 DI 10.1016/0014-5793(94)00888-4 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA PG938 UT WOS:A1994PG93800019 PM 8082799 ER PT J AU SAITO, K MARKEY, SP HEYES, MP AF SAITO, K MARKEY, SP HEYES, MP TI 6-CHLORO-D,L-TRYPTOPHAN, 4-CHLORO-3-HYDROXYANTHRANILATE AND DEXAMETHASONE ATTENUATE QUINOLINIC ACID ACCUMULATION IN BRAIN AND BLOOD FOLLOWING SYSTEMIC IMMUNE ACTIVATION SO NEUROSCIENCE LETTERS LA English DT Article DE QUINOLINIC ACID; INDOLEAMINE-2,3-DIOXYGENASE; 3-HYDROXYANTHRANILATE-3,4-DIOXYGENASE; DEXAMETHASONE; 6-CHLORO-D,L-TRYPTOPHAN; 4-CHLORO-3-HYDROXYANTHRANILIC ACID; BRAIN; BLOOD ID CEREBROSPINAL-FLUID; 3-HYDROXYANTHRANILIC ACID; NEUROACTIVE KYNURENINES; RAT-BRAIN; METABOLISM; DISEASE; 6-CHLOROTRYPTOPHAN; OXIDASE; PATHWAY; SERUM AB Accumulations of the neurotoxin quinolinic acid (QUIN) occur in the brain and blood following immune activation and are attributed to increased metabolism of L-tryptophan through the kynurenine pathway. Systemic administration of 4-chloro-3-hydroxyanthranilate (an inhibitor of 3-hydroxyanthranilate-3,4-dioxygenase), 6-chloro-D,L-tryptophan (a substrate of the kynurenine pathway) and dexamethasone (an anti-inflammatory agent) attenuated the accumulation of QUIN in the brain and blood following systemic pokeweed mitogen administration to mice. 6-Chloro-D,L-tryptophan and dexamethasone also attenuated the increases in brain and lung indoleamine-2,3-dioxygenase activity and elevations in plasma L-kynurenine levels. We conclude that QUIN formation can be modified by drugs which act at different levels of the cascade of events that link immune stimulation to increased kynurenine pathway metabolism. C1 NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,BETHESDA,MD 20892. NR 22 TC 23 Z9 24 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 12 PY 1994 VL 178 IS 2 BP 211 EP 215 DI 10.1016/0304-3940(94)90761-7 PG 5 WC Neurosciences SC Neurosciences & Neurology GA PH039 UT WOS:A1994PH03900009 PM 7824198 ER PT J AU NEIDIGH, KA GHARPURE, MM RIMOLDI, JM KINGSTON, DGI JIANG, YQ HAMEL, E AF NEIDIGH, KA GHARPURE, MM RIMOLDI, JM KINGSTON, DGI JIANG, YQ HAMEL, E TI SYNTHESIS AND BIOLOGICAL EVALUATION OF 4-DEACETYLPACLITAXEL SO TETRAHEDRON LETTERS LA English DT Article ID ANTITUMOR AGENTS; BACCATIN-III; SIDE-CHAINS; TAXOL; CHEMISTRY; TAXANES; REARRANGEMENT AB 4-Deacetylpaclitaxel, prepared from baccatin III via two synthetic approaches and from paclitaxel via one synthetic approach, has minimal effects on tubulin polymerization and is not cytotoxic to human CA46 Burkitt lymphoma cells. C1 VIRGINIA POLYTECH INST & STATE UNIV,DEPT CHEM,BLACKSBURG,VA 24061. NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. OI Kingston, David/0000-0001-8944-246X NR 18 TC 38 Z9 39 U1 1 U2 3 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 SEP 12 PY 1994 VL 35 IS 37 BP 6839 EP 6842 DI 10.1016/0040-4039(94)85018-6 PG 4 WC Chemistry, Organic SC Chemistry GA PG620 UT WOS:A1994PG62000017 ER PT J AU CHORDIA, MD CHAUDHARY, AG KINGSTON, DGI JIANG, YQ HAMEL, E AF CHORDIA, MD CHAUDHARY, AG KINGSTON, DGI JIANG, YQ HAMEL, E TI SYNTHESIS AND BIOLOGICAL EVALUATION OF 4-DEACETOXYPACLITAXEL SO TETRAHEDRON LETTERS LA English DT Article ID ANTITUMOR AGENTS; TAXOL; CHEMISTRY; CANCER; DRUG AB 4-Deacetoxypaclitaxel (9) has been prepared in seven steps from paclitaxel (Taxol(R)). It is significantly less active than paclitaxel in tubulin-assembly and cytotoxicity bioassays. C1 VIRGINIA POLYTECH INST & STATE UNIV,DEPT CHEM,BLACKSBURG,VA 24061. NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. RI Chordia, Mahendra/A-4706-2008; OI Kingston, David/0000-0001-8944-246X NR 21 TC 32 Z9 33 U1 0 U2 3 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 SEP 12 PY 1994 VL 35 IS 37 BP 6843 EP 6846 DI 10.1016/0040-4039(94)85019-4 PG 4 WC Chemistry, Organic SC Chemistry GA PG620 UT WOS:A1994PG62000018 ER PT J AU BERRY, MJ HARNEY, JW OHAMA, T HATFIELD, DL AF BERRY, MJ HARNEY, JW OHAMA, T HATFIELD, DL TI SELENOCYSTEINE INSERTION OR TERMINATION - FACTORS AFFECTING UGA CODON FATE AND COMPLEMENTARY ANTICODON-CODON MUTATIONS SO NUCLEIC ACIDS RESEARCH LA English DT Article ID I IODOTHYRONINE DEIODINASE; MESSENGER-RNA; GLUTATHIONE-PEROXIDASE; TRANSLATION FACTOR; GENETIC-CODE; PROTEIN; IDENTIFICATION; SELENOPROTEIN; EXPRESSION; ELEMENTS AB Translation of UGA as selenocysteine instead of termination occurs in numerous proteins, and the process of recoding UGA requires specific signals in the corresponding mRNAs. In eukaryotes, stem - loops in the 3' untranslated region of the mRNAs confer this function. Despite the presence of these signals, selenocysteine incorporation is inefficient. To investigate the reason for this, we examined the effects of the amount of deiodinase cDNA on UGA readthrough in transfected cells, quantitating the full-length and UGA terminated products by Western blotting. The gene for the selenocysteine-specific tRNA was also cotransfected to determine if it was limiting. We find that the concentrations of both the selenoprotein DNA and the tRNA affect the ratio of selenocysteine incorporation to termination. Selenium depletion was also found to decrease readthrough. The fact that the truncated peptide is synthesized intracellularly demonstrates unequivocally that UGA can serve as both a stop and a selenocysteine codon in a single mRNA. Mutation of UGA to UAA (stop) or UUA (leucine) in the deiodinase mRNA abolishes deiodinase activity; but activity is partially restored when selenocysteine tRNAs containing complementary mutations are cotransfected. Thus, UGA is not essential for selenocysteine incorporation in mammalian cells, provided that codon:anticodon complementarity is maintained. C1 NATL CANC INST,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. RP BERRY, MJ (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV THYROID,BOSTON,MA 02115, USA. FU NIDDK NIH HHS [DK45944, DK36256] NR 26 TC 87 Z9 87 U1 0 U2 5 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP 11 PY 1994 VL 22 IS 18 BP 3753 EP 3759 DI 10.1093/nar/22.18.3753 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PJ874 UT WOS:A1994PJ87400015 PM 7937088 ER PT J AU EASTERWOOD, TR MAJOR, F MALHOTRA, A HARVEY, SC AF EASTERWOOD, TR MAJOR, F MALHOTRA, A HARVEY, SC TI ORIENTATIONS OF TRANSFER-RNA IN THE RIBOSOMAL A-SITE AND P-SITE SO NUCLEIC ACIDS RESEARCH LA English DT Article ID 2 TRANSFER-RNAS; MESSENGER-RNA; 3-DIMENSIONAL STRUCTURE; ANTICODON LOOP; CROSS-LINKING; A-SITE; IDENTIFICATION; TRANSLOCATION; CROSSLINKING; ARRANGEMENT AB In protein synthesis, peptide bond formation requires that the tRNA carrying the amino acid (A site tRNA) contact the tRNA carrying the growing peptide chain (P site tRNA) at their 3' termini. Two models have been proposed for the orientations of two tRNAs as they would be bound to the mRNA in the ribosome. Viewing the tRNA as an upside down L, anticodon loop pointing down, acceptor stem pointing right, and calling this the front view, the R (Rich) model would have the back of the P site tRNA facing the front of the A site tRNA. In the S (Sundaralingam) model the front of the P site tRNA faces the back of the A site tRNA. Models of two tRNAs bound to mRNA as they would be positioned in the ribosomal A and P sites have been created using MC-SYM, a constraint satisfaction search program designed to build nucleic acid structures. The models incorporate information from fluorescence energy transfer experiments and chemical crosslinks. The models that best answer the constraints are of the S variety, with no R conformations produced consistent with the constraints. C1 UNIV ALABAMA,DEPT BIOCHEM & MOLEC GENET,BIRMINGHAM,AL 35294. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. RI Malhotra, Arun/A-3916-2008 OI Malhotra, Arun/0000-0001-6656-7841 NR 31 TC 21 Z9 23 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 SEP 11 PY 1994 VL 22 IS 18 BP 3779 EP 3786 DI 10.1093/nar/22.18.3779 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PJ874 UT WOS:A1994PJ87400019 PM 7937092 ER PT J AU TOLEDANO, MB KULLIK, I TRINH, F BAIRD, PT SCHNEIDER, TD STORZ, G AF TOLEDANO, MB KULLIK, I TRINH, F BAIRD, PT SCHNEIDER, TD STORZ, G TI REDOX-DEPENDENT SHIFT OF OXYR-DNA CONTACTS ALONG AN EXTENDED DNA-BINDING SITE - A MECHANISM FOR DIFFERENTIAL PROMOTER SELECTION SO CELL LA English DT Article ID ESCHERICHIA-COLI; TRANSCRIPTIONAL REGULATOR; POSITIVE REGULATOR; OXIDATIVE STRESS; INDUCIBLE GENES; NOD BOX; PROTEIN; RECOGNITION; EXPRESSION; ACTIVATOR AB The redox-sensitive OxyR protein activates the transcription of antioxidant defense genes in response to oxidative stress and represses its own expression under both oxidizing and reducing conditions. Previous studies showed that OxyR-binding sites are unusually long with limited sequence similarity. Here, we report that oxidized OxyR recognizes a motif comprised of four ATAGnt elements spaced at 10 bp intervals and contacts these elements in four adjacent major grooves on one face of the DNA helix. In contrast, reduced OxyR contacts two pairs of adjacent major grooves separated by one helical turn. The two modes of binding are essential for OxyR to function as both an activator and a repressor in vivo. We propose that specific DNA recognition by an OxyR tetramer is achieved with four contacts of intermediate affinity allowing OxyR to reposition its DNA contacts and target alternate sets of promoters as the cellular redox state is altered. C1 NCI,MATH BIOL LAB,FREDERICK,MD 21702. RP TOLEDANO, MB (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. OI Schneider, Thomas/0000-0002-9841-1531; Storz, Gisela/0000-0001-6698-1241 NR 26 TC 281 Z9 286 U1 2 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD SEP 9 PY 1994 VL 78 IS 5 BP 897 EP 909 DI 10.1016/S0092-8674(94)90702-1 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PG296 UT WOS:A1994PG29600018 PM 8087856 ER PT J AU CALABRO, A HASCALL, VC AF CALABRO, A HASCALL, VC TI DIFFERENTIAL-EFFECTS OF BREFELDIN-A ON CHONDROITIN SULFATE AND HYALURONAN SYNTHESIS IN RAT CHONDROSARCOMA CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANS-GOLGI NETWORK; PROTEOGLYCAN CORE PROTEIN; ENDOPLASMIC-RETICULUM; CULTURED CHONDROCYTES; EMBRYONIC CHICKEN; GRANULOSA-CELLS; LINKAGE REGION; BIOSYNTHESIS; CARTILAGE; OLIGOSACCHARIDES AB Brefeldin A, a fungal metabolite, interferes with vesicular transport causing disassembly of the Golgi complex with redistribution of Golgi components to the endoplasmic reticulum, and isolation of the trans-Golgi cisternae from the trans-Golgi network. We examined the effects of brefeldin A on the synthesis of hyaluronan and chondroitin sulfate by chondrocytes from the Swarm rat chondrosarcoma. Hyaluronan synthesis continues at a constant rate in the presence of brefeldin A for at least 8 h, and is therefore independent of vesicular transport. By contrast, chondroitin sulfate synthesis is rapidly inhibited (to <1% within 15 min) by brefeldin A indicating that addition of chondroitin sulfate chains to the aggrecan core protein precursor requires vesicular transport. Removal of brefeldin A rapidly restored chondroitin sulfate chain elongation and sulfation on the aggrecan core protein precursor reaching 100% of control in 2 h and consistently establishing a higher steady state rate (up to 120%) by 4 h. Addition of p-nitrophenyl-beta-D-xylopyranoside, an exogenous acceptor for the synthesis of chondroitin sulfate chains, does not reverse the brefeldin A block. This suggests that xyloside-initiated synthesis of chondroitin sulfate depends on transport vesicles as might occur if the enzymes for synthesizing the Linkage tetrasaccharide (i.e. galactosyltransferases) reside in the Golgi, while those required to elongate the chains reside in the trans-Golgi network. Recovery of chondroitin sulfate synthesis from brefeldin A treatment occurred efficiently in the presence of cycloheximide, indicating that the machinery for chondroitin sulfate synthesis reassembles from previously existing proteins. The results are consistent with the current model that hyaluronan synthesis occurs at the plasma membrane and is independent of vesicular transport, and with the hypothesis that the enzyme complex for chondroitin sulfate elongation and sulfation resides within the trans-Golgi network, and therefore isolated from the aggrecan core protein precursor in the presence of brefeldin A. C1 NIDR, BONE RES BRANCH, PROTEOGLYCAN CHEM SECT, BETHESDA, MD 20892 USA. NR 51 TC 25 Z9 25 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 SEP 9 PY 1994 VL 269 IS 36 BP 22764 EP 22770 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ163 UT WOS:A1994PQ16300048 PM 8077228 ER PT J AU CALABRO, A HASCALL, VC AF CALABRO, A HASCALL, VC TI EFFECTS OF BREFELDIN-A ON AGGRECAN CORE PROTEIN-SYNTHESIS AND MATURATION IN RAT CHONDROSARCOMA CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANS-GOLGI NETWORK; CARTILAGE PROTEOGLYCAN; CULTURED CHONDROCYTES; ARTICULAR-CARTILAGE; BIOSYNTHESIS; CYCLOHEXIMIDE; FIBRONECTIN; EXPRESSION; CISTERNAE; COMPLEX AB In this paper, the effects of the fungal metabolite, brefeldin A, on the synthesis and maturation of aggrecan core protein precursor were studied in rat chondrosarcoma chondrocytes. The aggrecan core protein precursor was partially identified in total protein pools isolated from cell extracts based on its selective cleavage at a single site by the restriction protease factor Xa. During a 2-h labeling period with [H-3]serine as precursor, brefeldin A inhibited the synthesis of mature aggrecan from its aggrecan core protein precursor consistent with an inhibition of chondroitin sulfate chain elongation and sulfation as described in the accompanying paper (Calabro, A., and Hascall, V. C. (1994) J. Biol Chem. 269, 22764-22770). This inhibition is presumably the result of the disruption of vesicular transport by brefeldin A, which isolates the aggrecan core protein precursor at the level of the trans-Golgi cisternae from the enzymes for chondroitin sulfate chain elongation and sulfation located in the trans-Golgi network. Brefeldin A also inhibited the exocytosis of all radiolabeled secretory proteins from the cell layer into the medium compartment, which is also consistent with the disruption of vesicular transport attributed to this metabolite. Although total protein synthesis was inhibited by 12% in the presence of brefeldin A, the aggrecan core protein precursor accumulated within the cell layer indicating that the inhibition of chondroitin sulfate synthesis by brefeldin A was not the result of a lack of aggrecan core protein precursor. When the brefeldin A block was removed and cultures chased in the presence of cycloheximide to prevent new protein synthesis, vesicular transport through the cell was re-established and chondroitin sulfate chains were added to a large proportion of the aggrecan core protein precursor that had accumulated during the brefeldin A block. These results suggest that the machinery for chondroitin sulfate synthesis and for protein exocytosis, that were disrupted by brefeldin A treatment, recover after removal of the brefeldin A, even in the presence of cycloheximide, and that the structures involved in these processes reassemble from previously existing proteins. Interestingly, two other proteins with the same relative abundance as the aggrecan core protein precursor were observed. An similar to 10 kDa protein with the characteristics of the fibronectin subunit, and an unidentified similar to 150-kDa protein which was efficiently cleaved by the protease Xa enzyme. C1 NIDR,BONE RES BRANCH,PROTEOGLYCAN CHEM SECT,BETHESDA,MD 20892. NR 17 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 9 PY 1994 VL 269 IS 36 BP 22771 EP 22778 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ163 UT WOS:A1994PQ16300049 PM 8077229 ER PT J AU PETTIT, GR XU, JP CICHACZ, ZA WILLIAMS, MD DORSAZ, AC BRUNE, DC BOYD, MR CERNY, RL AF PETTIT, GR XU, JP CICHACZ, ZA WILLIAMS, MD DORSAZ, AC BRUNE, DC BOYD, MR CERNY, RL TI ANTINEOPLASTIC AGENTS .315. ISOLATION AND STRUCTURE OF THE MARINE SPONGE CANCER CELL-GROWTH INHIBITOR PHAKELLISTATIN-5 SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID SOLUTION-STATE; PEPTIDES; SEPARATION; ANALOGS; PHASE; LINE AB The Federated State of Micronesia (Chuuk) marine sponge Phakellia costada has been found to contain (9.6 x 10(-6) % yield) a new human cancer cell growth inhibitor designated phakellistatin 5 (3). Structural elucidation was accomplished employing high resolution FAB tandem MS/MS and high field (500 MHz) 2D-NMR techniques. Extension of the NMR experiments over the temperature range -25 to 25 degrees C allowed the principal solution conformation of phakellistatin 5 to be assigned (Figure 2). The absolute configuration was found to correspond to S-amino acid units except for R-Asn. C1 ARIZONA STATE UNIV, DEPT CHEM, TEMPE, AZ 85287 USA. NCI, FREDERICK CANC RES & DEV CTR, DIV CANC TREATMENT, DEV THERAPEUT PROGRAM, FREDERICK, MD 21702 USA. UNIV NEBRASKA, DEPT CHEM, MIDWEST CTR MASS SPECT, LINCOLN, NE 68588 USA. RP PETTIT, GR (reprint author), ARIZONA STATE UNIV, CENT RES INST, TEMPE, AZ 85287 USA. NR 25 TC 25 Z9 25 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD SEP 8 PY 1994 VL 4 IS 17 BP 2091 EP 2096 DI 10.1016/S0960-894X(01)80108-6 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA PG041 UT WOS:A1994PG04100006 ER PT J AU MAGIAKOU, MA MASTORAKOS, G OLDFIELD, EH GOMEZ, MT DOPPMAN, JL CUTLER, GB NIEMAN, LK CHROUSOS, GP AF MAGIAKOU, MA MASTORAKOS, G OLDFIELD, EH GOMEZ, MT DOPPMAN, JL CUTLER, GB NIEMAN, LK CHROUSOS, GP TI CUSHINGS-SYNDROME IN CHILDREN AND ADOLESCENTS - PRESENTATION, DIAGNOSIS, AND THERAPY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; DIFFERENTIAL-DIAGNOSIS; STIMULATION TEST; FREE CORTISOL; DISEASE; CHILDHOOD; MICROADENOMAS AB Background and Methods. Cushing's syndrome is rare in children and adolescents. We analyzed the clinical presentation, diagnostic evaluation, and treatment of 59 patients with Cushing's syndrome between the ages of 4 and 20 years who were admitted to the National Institutes of Health during the period from 1982 to 1992. The cause of hypercortisolism was identified by low- and high-dose dexamethasone suppression tests, the ovine corticotropin-releasing hormone (CRH) stimulation test, imaging studies, and bilateral sampling of the inferior petrosal sinuses combined with administration of CRH. Results. Fifty patients had Cushing's disease, six had primary adrenal disease, and three had ectopic corticotropin secretion. The initial signs were excessive weight gain in 90 percent of the patients and growth retardation in 83 percent. Most patients (81 percent) had normal bone age at the time of diagnosis. Forty-seven percent had hypertension, whereas only 19 percent had mental or behavioral problems. The high-dose dexamethasone suppression test and the CRH stimulation test identified 68 and 80 percent, respectively, of the patients with Cushing's disease. Magnetic resonance imaging of the pituitary indicated the presence of tumor in 52 percent of the patients with pituitary adenomas. The maximal central-to-peripheral ratio of plasma corticotropin during sampling of the interior petrosal sinuses was greater than or equal to 2.5 in all the patients with Cushing's disease and <2.5 in those with ectopic corticotropin secretion. Remission of hypercortisolism was achieved in 48 of the 49 patients who underwent transsphenoidal surgery for Cushing's disease, in all 6 of the patients who underwent adrenalectomy for primary adrenal disease, and in the 2 patients in whom the ectopic source of corticotropin could be identified. Conclusions. Weight gain and growth retardation are common clinical characteristics of Cushing's syndrome in children and adolescents. Diagnostic evaluation of such patients with CRH stimulation alone and combined with inferior petrosal sinus sampling and imaging studies is accurate, and therapy is usually successful. C1 NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. NIH,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. RP MAGIAKOU, MA (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,RM 10N262,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 33 TC 226 Z9 232 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 8 PY 1994 VL 331 IS 10 BP 629 EP 636 DI 10.1056/NEJM199409083311002 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA PE382 UT WOS:A1994PE38200002 PM 8052272 ER PT J AU ZHU, G LIVE, D BAX, A AF ZHU, G LIVE, D BAX, A TI ANALYSIS OF SUGAR PUCKERS AND GLYCOSIDIC TORSION ANGLES IN A DNA G-TETRAD STRUCTURE BY HETERONUCLEAR 3-BOND J-COUPLINGS SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Note ID TELOMERIC DNA; NUCLEIC-ACIDS; 2D NMR; CONSTANTS; ASSIGNMENT; OLIGONUCLEOTIDES; CONFORMATIONS; ORIENTATION; SPECTRA; COMPLEX C1 MEM SLOAN KETTERING CANC CTR,CELLULAR BIOCHEM & BIOPHYS PROGRAM,NEW YORK,NY 10021. UNIV MARYLAND,DEPT ELECT ENGN,COLLEGE PK,MD 20874. NIDDK,CHEM PHYS LAB,BETHESDA,MD 20892. NR 26 TC 49 Z9 49 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD SEP 7 PY 1994 VL 116 IS 18 BP 8370 EP 8371 DI 10.1021/ja00097a056 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA PF913 UT WOS:A1994PF91300056 ER PT J AU LONDON, RE LEMASTER, DM WERBELOW, LG AF LONDON, RE LEMASTER, DM WERBELOW, LG TI UNUSUAL NMR MULTIPLET STRUCTURES OF SPIN-1/2 NUCLEI COUPLED TO SPIN-1 NUCLEI SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Note ID QUADRUPOLAR; RELAXATION; PROTEINS C1 CTR ST JEROME,METHODES SPECT LAB,F-13397 MARSEILLE 13,FRANCE. NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. NORTHWESTERN UNIV,DEPT BIOCHEM MOLEC BIOL & CELL BIOL,EVANSTON,IL 60208. NR 20 TC 38 Z9 38 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD SEP 7 PY 1994 VL 116 IS 18 BP 8400 EP 8401 DI 10.1021/ja00097a071 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA PF913 UT WOS:A1994PF91300071 ER PT J AU ACOSTA, K CESSAC, JW RAO, PN KIM, HK AF ACOSTA, K CESSAC, JW RAO, PN KIM, HK TI OXIDATIVE DEMETHYLATION OF 4-SUBSTITUTED N,N-DIMETHYLANILINES WITH IODINE AND CALCIUM-OXIDE IN THE PRESENCE OF METHANOL SO JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS LA English DT Article ID OXYGEN ATOM TRANSFER; TERTIARY-AMINES; DRUG-METABOLISM; CYTOCHROME-P-450; MODEL; DEALKYLATION; SYSTEM AB Reaction of para-substituted N,N-dimethylarylamines with iodine-calcium oxide in tetrahydrofuran-methanol affords N-methylarylamines in good yield. C1 SW FDN BIOMED RES,DEPT ORGAN CHEM,SAN ANTONIO,TX 78228. NICHHD,BETHESDA,MD 20892. NR 14 TC 17 Z9 17 U1 1 U2 2 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 SEP 7 PY 1994 IS 17 BP 1985 EP 1986 DI 10.1039/c39940001985 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA PF544 UT WOS:A1994PF54400039 ER PT J AU MELTZER, PS AF MELTZER, PS TI MDM2 AND P53 - A QUESTION OF BALANCE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID HUMAN SARCOMAS; GENE AMPLIFICATION; PROTEIN; EXPRESSION; CHOP RP MELTZER, PS (reprint author), NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892, USA. NR 24 TC 44 Z9 47 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 7 PY 1994 VL 86 IS 17 BP 1265 EP 1266 DI 10.1093/jnci/86.17.1265 PG 2 WC Oncology SC Oncology GA PE331 UT WOS:A1994PE33100001 PM 8064885 ER PT J AU GOTTESMAN, MM AF GOTTESMAN, MM TI REPORT OF A MEETING - MOLECULAR-BASIS OF CANCER-THERAPY SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID MULTIDRUG-RESISTANCE; GENE; RAS; TRANSPORTER; METASTASIS; REGION RP GOTTESMAN, MM (reprint author), NCI,DIV CANC BIOL DIAG & CTR,CELL BIOL LAB,BLDG 37,RM 1B22,BETHESDA,MD 20892, USA. NR 49 TC 21 Z9 22 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 7 PY 1994 VL 86 IS 17 BP 1277 EP 1285 DI 10.1093/jnci/86.17.1277 PG 9 WC Oncology SC Oncology GA PE331 UT WOS:A1994PE33100009 PM 7914937 ER PT J AU PILI, R GUO, Y CHANG, J NAKANISHI, H MARTIN, GR PASSANITI, A AF PILI, R GUO, Y CHANG, J NAKANISHI, H MARTIN, GR PASSANITI, A TI ALTERED ANGIOGENESIS UNDERLYING AGE-DEPENDENT CHANGES IN TUMOR-GROWTH SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CAPILLARY-LIKE STRUCTURES; HUMAN-ENDOTHELIAL CELLS; COLON-CARCINOMA CELLS; HUMAN-MELANOMA CELLS; BASEMENT-MEMBRANE; EXTRACELLULAR-MATRIX; CANCER INCIDENCE; QUINOLINE-3-CARBOXAMIDE LINOMIDE; DIETARY RESTRICTION; BREAST-CANCER AB Background: Cancer incidence increases with age, but the growth and spread of tumors is often slow and prolonged in the elderly. Transplantable murine tumors grow and spread less readily in older mice and can be used as models to study the effect of host age. Neovascularization is crucial for the growth of solid tumors, and alterations in the host vascular response may underlie the changes in tumor growth occurring with age. Purpose: We have used transplantable tumor cells and tumors, and tumor extracts, to better understand differences in the biology of tumor growth and vascularization as a function of host age. Methods: Englebreth-Holm-Swarm (EHS) carcinoma and B16-F10 melanoma cells mere injected into C57BL mice of different ages. Tumor growth, histology, and cellular DNA synthesis were compared. Vascularization mas determined using basic fibroblast growth factor and an in vivo angiogenesis assay. EHS tumor extracts mere assayed for biologic activity in vitro using human endothelial cells and in vivo using mouse EHS-BAM carcinoma and human TSU-Pr1 prostate carcinoma cells. Results: EHS tumors formed larger tumors in young than in old C57BL mice. Rapid tumor growth resumed upon transfer of tumor tissue from old animals into young animals. The rate of DNA synthesis of tumor tissue from old animals in organ culture mas lower than in tissue from young animals. Histologically, tumors grown in old animals exhibited a threefold higher ratio of extracellular matrix to tumor cells than those grown in young animals. Tumors from adult animals exhibited numerous small blood vessels; those from old animals contained fewer, much larger vessels. Similar results mere observed in young mice fed a reduced-calorie diet. Young animals elicited a greater and more rapid angiogenic response than old animals. Extracts of tumors grown in old animals failed to support endothelial cell differentiation in culture. Tumor cells injected together with such old extracts showed reduced tumor growth in nude mice. Conclusions: The rate of growth and morphology of the EHS tumor were altered with age, partly due to a reduced capacity to vascularize the tumors because of a lack of angiogenic factors or the presence of host inhibitors. Implications: Alterations in host factors detected in this tumor model may underlie a variety of age-dependent changes that could influence tumor growth and the repair and regeneration of normal tissue. Reducing the vascularization of tumors represents a potential target to reduce their growth and progression. C1 NIA,GERONTOL RES CTR,BIOL CHEM LAB,CELL BIOL UNIT,BALTIMORE,MD 21224. NR 48 TC 88 Z9 89 U1 0 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 7 PY 1994 VL 86 IS 17 BP 1303 EP 1314 DI 10.1093/jnci/86.17.1303 PG 12 WC Oncology SC Oncology GA PE331 UT WOS:A1994PE33100012 PM 7520508 ER PT J AU CURTIS, RE BOICE, JD STOVALL, M BERNSTEIN, L HOLOWATY, E KARJALAINEN, S LANGMARK, F NASCA, PC SCHWARTZ, AG SCHYMURA, MJ STORM, HH TOOGOOD, P WEYER, P MOLONEY, WC AF CURTIS, RE BOICE, JD STOVALL, M BERNSTEIN, L HOLOWATY, E KARJALAINEN, S LANGMARK, F NASCA, PC SCHWARTZ, AG SCHYMURA, MJ STORM, HH TOOGOOD, P WEYER, P MOLONEY, WC TI RELATIONSHIP OF LEUKEMIA RISK TO RADIATION-DOSE FOLLOWING CANCER OF THE UTERINE CORPUS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SINGLE TREATMENT COURSE; MATCHED CASE-CONTROL; ANKYLOSING-SPONDYLITIS; MULTIPLE-MYELOMA; CHILDHOOD-CANCER; HODGKINS-DISEASE; BREAST-CANCER; X-RAYS; RADIOTHERAPY; MORTALITY AB Background: Radiotherapy has been linked infrequently to secondary leukemia despite extensive exposure of the active bone marrow to ionizing radiation. Few studies include substantial numbers of elderly patients. Purpose: We evaluated women with cancer of the uterine corpus, the majority of whom were treated at older ages, to gain additional information on cancer risk following partial-body radiotherapy and to examine differences in risk between external-beam therapy and brachytherapy. Methods: A cohort of 110 000 women with invasive cancer of the uterine corpus who survived at least 1 year following their initial cancer was assembled from nine population-based cancer registries. Cancer diagnoses occurred from 1935 through 1985, and most patients were diagnosed during the 1960s and 1970s. Radiation doses were computed to 17 sections of the active bone marrow for 218 women who developed leukemia and for 775 matched control subjects. Results: Radiotherapy did not increase the risk of chronic lymphocytic leukemia (CLL) (relative risk [RR] = 0.90; 95% confidence interval [CI] 0.4-1.9). However, for all leukemias except CLL, a significant risk was identified (RR = 1.92; 95% CI = 1.3-2.9). Overall, the pattern of risk in relation to dose was erratic and was most consistent with a constant increased risk across the entire dose range. The risk following continuous exposures from brachytherapy at comparatively low doses and low dose rates (RR = 1.80; 95% CI = 1.1-2.8; mean dose = 1.72 Gy) was similar to that after fractionated exposures at much higher doses and higher dose rates from external-beam treatment (RR = 2.29; 95% CI = 1.4-3.7; mean dose = 9.88 Gy), indicating a large difference in the estimated risk per unit dose. Risk did not vary by age at first exposure; increased risks were apparent for irradiated patients aged 65 years or older (RR = 1.77; 95% CI = 0.9-3.5). Conclusion: The leukemia risk associated with partial-body radiotherapy for uterine corpus cancer was small; about 14 excess leukemia cases mere due to radiation per 10 000 women followed for 10 years. Women aged 65 years or older had a radiation risk comparable with that found in younger women. The relationship of leukemia risk to radiation dose was found to be complex due to the competing processes of cell killing, transformation, and repair. At very high doses delivered at high rates, destruction of cells likely dominates, and the risk per unit dose is low. In the low dose range, where dose was protracted and delivered at relatively low dose rates, the leukemia risk appears lower than that projected from risk estimates derived from the instantaneous whole-body exposures of atomic bomb survivors. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT RADIAT PHYS,HOUSTON,TX 77030. UNIV SO CALIF,SCH MED,LOS ANGELES,CA. ONTARIO CANC TREATMENT & RES FDN,TORONTO,ON,CANADA. FINNISH CANC REGISTRY,SF-00170 HELSINKI,FINLAND. NORWEGIAN RADIUM HOSP,CANC REGISTRY NORWAY,OSLO,NORWAY. NEW YORK STATE DEPT HLTH,ALBANY,NY 12201. MICHIGAN CANC FDN,DETROIT,MI 48201. YALE UNIV,NEW HAVEN,CT. DANISH CANC SOC,DIV CANC EPIDEMIOL,COPENHAGEN,DENMARK. STATE HLTH REGISTRY IOWA,IOWA CITY,IA. HARVARD UNIV,SCH MED,BOSTON,MA. RP CURTIS, RE (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,RADIAT EPIDEMIOL BRANCH,EXECUT PLAZA N,SUITE 408,BETHESDA,MD 20892, USA. NR 35 TC 77 Z9 78 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 SEP 7 PY 1994 VL 86 IS 17 BP 1315 EP 1324 DI 10.1093/jnci/86.17.1315 PG 10 WC Oncology SC Oncology GA PE331 UT WOS:A1994PE33100013 PM 8064889 ER PT J AU BROWN, LM HOOVER, RN GREENBERG, RS SCHOENBERG, JB SCHWARTZ, AG SWANSON, GM LIFF, JM SILVERMAN, DT HAYES, RB POTTERN, LM AF BROWN, LM HOOVER, RN GREENBERG, RS SCHOENBERG, JB SCHWARTZ, AG SWANSON, GM LIFF, JM SILVERMAN, DT HAYES, RB POTTERN, LM TI ARE RACIAL-DIFFERENCES IN SQUAMOUS-CELL ESOPHAGEAL CANCER EXPLAINED BY ALCOHOL AND TOBACCO USE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RELATIVE-RISK MODELS; LUNG-CANCER; POLYMORPHISM; ALLELES; LOCUS AB Background: In the United States, incidence rates of squamous cell esophageal cancer are more than five times higher among black men than among white men. Reasons that might explain this large racial disparity are being sought. Purpose: We evaluated whether differential use of alcohol and tobacco can fully account for the excess of squamous cell esophageal cancer among U.S. blacks. Methods: We conducted a population-based, case-control study with in-person interviews with 373 squamous cell esophageal cancer case patients (124 white males and 249 black males) and 1364 control subjects (750 white males and 614 black males) from three U.S. geographic areas. Histologically confirmed cases of squamous cell esophageal cancer newly diagnosed from August 1, 1986, through April 30, 1989, among white and black men aged 30-79 years were included. Results: Alcohol use of more than one drink per day and/or current cigarette use of at least one pack per day accounted for 92.7% (95% confidence interval [CI] = 86.8%-98.5%) of the squamous cell esophageal cancers in blacks, versus 86.3% (95% CI = 75.5%-97.1%) in whites, and for 93% of the difference between the black and white annual incidence rates. The interaction between race and the continuous drinking/smoking variable in a logistic regression analysis a-as statistically significant (two-sided, P = .02). Exposure rates among controls at all levels of combined alcohol and tobacco use examined were slightly higher among blacks and accounted for a small portion of the racial differences in incidence rates. Conclusion: Although the vast majority of esophageal cancers in both blacks and whites in our data can be explained by use of alcohol and tobacco, it is not clear why heavy consumption of alcohol and/or tobacco is responsible for 14.9 per 100 000 per year more cases of squamous cell esophageal cancer among blacks than among whites. The differences in the odds ratios appear to account for more of the racial differences in incidence rates than do the prevalences of exposure to alcohol and tobacco alone. The reasons for this apparent racial difference in carcinogenic risk from the same level of alcohol and tobacco use are unknown, but they may include qualitative differences in alcohol consumption, differences in other environmental exposures that interact with alcohol and/or tobacco to modify risks, or differences in susceptibility to these factors. C1 EMORY UNIV,SCH PUBL HLTH,DIV EPIDEMIOL,ATLANTA,GA. NEW JERSEY STATE DEPT HLTH,SPECIAL EPIDEMIOL PROGRAM,TRENTON,NJ. UNIV PITTSBURGH,SCH MED,DEPT CLIN EPIDEMIOL & FAMILY MED,PITTSBURGH,PA. MICHIGAN STATE UNIV,COLL HUMAN MED,E LANSING,MI 48824. 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 [N01CP51089, N01CP51090, N01CP51092] NR 24 TC 63 Z9 63 U1 0 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 SEP 7 PY 1994 VL 86 IS 17 BP 1340 EP 1345 DI 10.1093/jnci/86.17.1340 PG 6 WC Oncology SC Oncology GA PE331 UT WOS:A1994PE33100017 PM 8064893 ER PT J AU GAIL, R BENICHOU, J AF GAIL, R BENICHOU, J TI VALIDATION OF THE GAIL ET-AL MODEL FOR PREDICTING INDIVIDUAL BREAST-CANCER RISK SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID SELECTION RP GAIL, R (reprint author), NCI,BIOSTAT BRANCH,DIV CANC ETIOL,EXECUT PLAZA N,SUITE 408,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 7 PY 1994 VL 86 IS 17 BP 1351 EP 1352 PG 2 WC Oncology SC Oncology GA PE331 UT WOS:A1994PE33100022 ER PT J AU LAM, WC MAKI, AH CASASFINET, JR ERICKSON, JW KANE, BP SOWDER, RC HENDERSON, LE AF LAM, WC MAKI, AH CASASFINET, JR ERICKSON, JW KANE, BP SOWDER, RC HENDERSON, LE TI PHOSPHORESCENCE AND OPTICALLY DETECTED MAGNETIC-RESONANCE INVESTIGATION OF THE BINDING OF THE NUCLEOCAPSID PROTEIN OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 AND RELATED PEPTIDES TO RNA SO BIOCHEMISTRY LA English DT Article ID TERMINAL ZINC FINGER; TRYPTOPHAN RESIDUES; STATE; HIV-1; ACID; RETROVIRUSES; COMPLEXES; ANALOG; SITE; SIV AB The RNA and DNA complexes of nucleocapsid protein p7.Zn (NCp7.Zn) of the human immunodeficiency virus type 1 (HIV-1) are studied by phosphorescence and optically detected magnetic resonance (ODMR). The single tryptophan, Trp37, which is located on the C-terminal zinc finger domain is used as an intrinsic probe. Reductions in the triplet state zero-field splitting (zfs) D parameter of Trp37 upon complex formation with poly(I) and poly(U) are observed. These results, in conjunction with the phosphorescence red-shifts and triplet state lifetime reductions that are observed, suggest the presence of aromatic stacking interactions between NCp7.Zn and the bases of the RNA polymers. An alteration of the intersystem crossing pattern upon complex formation, in addition to the above mentioned spectroscopic shifts, also is consistent with previously observed tryptophans that undergo stacking interactions with DNA bases [Zang, L.-H., Maki, A. H., Murphy, J. B., and Chase, J. W. (1987) Biophys. J. 52, 867-872. Tsao, D. H. H., Casas-Finet, J. R., Maki, A. H., and Chase, J. W. (1989) Biophys. J. 55, 927-936]. These conclusions support those from a recent ODMR study [Lam, W.-C., Maki, A. H., Casas-Finet, J. R., Erickson, J. W., Sowder, R. C., II, and Henderson, L. E. (1993) FEBS Lett. 328, 45-48] of NCp7.Zn binding to 5-mercurated polyuridylic acid [poly(5-HgU)] in which stacking interactions between the RNA and NCp7.Zn are inferred from the observation of an external heavy atom effect induced on Trp37. The extent of the spectroscopic effects observed varies with different RNA complexes; the phosphorescence red-shifts, for instance, correlate with the affinities of NCp7.Zn for various RNA bases as measured by fluorescence quenching experiments [Casas-Finet, J. R., Sowder, R. C., II, Sakaguchi, K., Appella, E., Henderson, L. E., and Erickson, J. W. (1993) Biophys. J. 64, A178]. The complexes of an 18mer synthetic second zinc finger peptide of NCp7 with RNA polymers gave results similar to NCp7.Zn, indicating that tryptophan in either the wild type protein or in the synthetic peptide experience similar environments. However, spectroscopic effects of smaller magnitude are observed in the synthetic second zinc finger peptide complexes, relative to those in the NCp7.Zn complexes, suggesting that the two zinc fingers in NCp7.Zn may act in concert to bind RNA, A synthetic carboxymethylated second zinc finger peptide in which a zinc finger structure cannot be formed also is studied. The triplet state properties observed for the uncomplexed synthetic carboxymethylated second zinc finger peptide are similar to those of the noncarboxymethylated synthetic second zinc finger peptide, suggesting that the tryptophans in the two fingers have similar environments in the uncomplexed form. When either poly(I) or poly(U) is added to the synthetic carboxymethylated second zinc finger peptide, practically no spectroscopic effects are observed, indicating weak or no interaction between Trp37 and the RNAs under experimental conditions similar to those used for NCp7.Zn and the synthetic second zinc finger peptide binding. C1 UNIV CALIF DAVIS,DEPT CHEM,DAVIS,CA 95616. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,AIDS VACCINE PROGRAM,FREDERICK,MD 21702. FU NIEHS NIH HHS [ES-02662] NR 28 TC 28 Z9 28 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 6 PY 1994 VL 33 IS 35 BP 10693 EP 10700 DI 10.1021/bi00201a017 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PF190 UT WOS:A1994PF19000017 PM 8075069 ER PT J AU MACHESKY, LM COLE, NB MOSS, B POLLARD, TD AF MACHESKY, LM COLE, NB MOSS, B POLLARD, TD TI VACCINIA VIRUS EXPRESSES A NOVEL PROFILIN WITH A HIGHER AFFINITY FOR POLYPHOSPHOINOSITIDES THAN ACTIN SO BIOCHEMISTRY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; 3-DIMENSIONAL SOLUTION STRUCTURE; BOUND ADENOSINE 5'-TRIPHOSPHATE; AMINO-ACID SEQUENCE; T7 RNA-POLYMERASE; ACANTHAMOEBA PROFILIN; PHOSPHOLIPASE-C; SACCHAROMYCES-CEREVISIAE; BINDING PROTEIN; HUMAN PLATELET AB We expressed in Escherichia coli the vaccinia virus gene for a protein similar to vertebrate profilins, purified the recombinant viral profilin, and characterized its interactions with actin and polyphosphoinositides. Compared with cellular profilins, this viral profilin has a low affinity (K-d greater than or equal to 35 mu M) for human platelet actin monomers, a weak effect on the exchange of the nucleotide bound to the actin, and no detectable affinity for poly(L-proline). Vaccinia profilin binds to phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4-monophosphate in micelles and large unilamellar vesicles, but not to phosphatidylserine or phosphatidylcholine. Kinetic analysis by surface plasmon resonance showed that both vaccinia and amoeba profilins bind slowly to polyphosphoinositides, with association rate constants in the range of (1-4) x 10(4) M(-1) s(-1). The higher affinity of vaccinia profilin for polyphosphoinositides (K-d = 0.2-8.5 mu M) than for actin or poly(L-proline) and the concentration of vaccinia profilin expressed in infected HeLa cells (similar to 20 mu M) suggest that vaccinia profilin binds preferentially to PIP and PIP2 in vivo. Consequently, vaccinia profilin is more likely to influence phosphoinositide metabolism than actin assembly. Expression of 7-105 mu M vaccinia profilin in a Saccharomyces cerevisiae profilin null mutant did not rescue the null phenotype, so that the affinity of vaccinia profilin for phosphoinositides alone is insufficient for normal profilin function in yeast. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT CELL BIOL & ANAT,BALTIMORE,MD 21205. NIH,VIRAL DIS LAB,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM-26338] NR 69 TC 39 Z9 41 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 6 PY 1994 VL 33 IS 35 BP 10815 EP 10824 DI 10.1021/bi00201a032 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PF190 UT WOS:A1994PF19000032 PM 8075084 ER PT J AU ZHANG, J HERMAN, EH FERRANS, VJ AF ZHANG, J HERMAN, EH FERRANS, VJ TI EFFECTS OF ICRF-186 [(L)1,2-BIS(3,5-DIOXOPIPERAZINYL-1-YL)PROPANE] ON THE TOXICITY OF DOXORUBICIN IN SPONTANEOUSLY HYPERTENSIVE RATS SO TOXICOLOGY LA English DT Article DE ICRF-186; DOXORUBICIN; CARDIOTOXICITY; NEPHROTOXICITY; IMMUNE CELLS; SHR RATS ID SYRIAN GOLDEN-HAMSTERS; ACUTE DAUNORUBICIN TOXICITY; RENAL TOXICITY; BREAST-CANCER; REDUCTION; CARDIOTOXICITY; (+)-1,2-BIS(3,5-DIOXOPIPERAZINYL-1-YL)PROPANE; PRETREATMENT; ADRIAMYCIN; WOMEN AB An evaluation was made of the protective effects of ICRF-186 [(L)1,2-bis(3,5-dioxopiperazinyl-1-yl)propane], the L-enantiomer of ICRF-187 [(D)1,2-bis(3,5-dioxopiperazinyl-1-yl)propane], against the cardiotoxicity and nephrotoxicity induced in spontaneously hypertensive rats (SHR) by doxorubicin. SHR were given doxorubicin (1 mg/kg, i.v.), once a week for 12 weeks. Group 1 (n = 10) received doxorubicin alone; Groups 2, 3 and 4 (each, n = 5) received ICRF-186, 25 mg/kg (group 2), 12.5 mg/kg (group 3) or 6.25 mg/kg (group 4), i.p., 30 min before each dose of doxorubicin. Two groups of control animals (each, n = 5) received 12 weekly i.p. injections of saline or 25 mg/kg ICRF-186. ICRF-186 provided significant protection, in a dose-dependent manner, against the cardiotoxicity and nephrotoxicity of doxorubicin and attenuated the increases in cardiac immune effector cells (interstitial dendritic cells, cytotoxic T-helper lymphocytes and macrophages) associated with this cardiotoxicity. The results of the study were compared with those obtained with ICRF-187 under identical experimental conditions. Analysis of the cardiomyopathy scores, nephropathy scores and counts of the numbers of immune effector cells in the heart showed that, at a dose of 25 mg/kg, ICRF-186 is a somewhat less effective protectant than ICRF-187. At a dose of 12.5 mg/kg, both compounds induced generally similar degrees of protection. At a dose of 6.25 mg/kg, both had comparable, but only minimal, protective effects. C1 US FDA, DIV RES & TESTING, LAUREL, MD 20708 USA. NHLBI, PATHOL BRANCH, BETHESDA, MD 20892 USA. NR 28 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD SEP 6 PY 1994 VL 92 IS 1-3 BP 179 EP 192 DI 10.1016/0300-483X(94)90176-7 PG 14 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA PK035 UT WOS:A1994PK03500014 PM 7940559 ER PT J AU LUSTER, MI PORTIER, C PAIT, DG GERMOLEC, DR AF LUSTER, MI PORTIER, C PAIT, DG GERMOLEC, DR TI USE OF ANIMAL STUDIES IN RISK ASSESSMENT FOR IMMUNOTOXICOLOGY SO TOXICOLOGY LA English DT Review DE IMMUNOTOXICOLOGY; RISK ASSESSMENT; HOST RESISTANCE TESTS; HUMAN RISK ASSESSMENT; IMMUNOSUPPRESSION; INTERPRETATION; IMMUNE FUNCTION TESTS ID GUIDELINES; TOXICOLOGY; IMMUNE; TESTS AB We have previously reported on the design and content of a screening battery involving a 'tier' approach for detecting potential immunosuppressive compounds in mice. This battery has been used to examine a variety of compounds, and the database generated from these studies, which consists of over 50 compounds, has been collected and analyzed in an attempt to improve the accuracy and efficiency of screening chemicals for immunosuppression and to identify better those tests that predict experimentally-induced, immune-mediated diseases. Specifically, these analyses attempted to develop an improved testing configuration for the accurate prediction of immunotoxic agents and to provide insight into the qualitative and quantitative relationships between a number of immune and host resistance assays commonly employed to examine potential immunotoxic chemicals in experimental animals. While a number of limitations existed in the analyses, several conclusions were drawn from the results which will be discussed. C1 NIEHS,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709. RP LUSTER, MI (reprint author), NIEHS,ENVIRONM IMMUNOL & NEUROBIOL SECT,RES TRIANGLE PK,NC 27709, USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 17 TC 22 Z9 22 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD SEP 6 PY 1994 VL 92 IS 1-3 BP 229 EP 243 DI 10.1016/0300-483X(94)90180-5 PG 15 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA PK035 UT WOS:A1994PK03500018 PM 7940563 ER PT J AU YAN, GM NI, BH WELLER, M WOOD, KA PAUL, SM AF YAN, GM NI, BH WELLER, M WOOD, KA PAUL, SM TI DEPOLARIZATION OR GLUTAMATE-RECEPTOR ACTIVATION BLOCKS APOPTOTIC CELL-DEATH OF CULTURED CEREBELLAR GRANULE NEURONS SO BRAIN RESEARCH LA English DT Article DE CEREBELLAR GRANULE NEURON; DEPOLARIZATION; POTASSIUM; APOPTOSIS; EXCITOTOXICITY; EXCITATORY AMINO ACID RECEPTOR ID METHYL-D-ASPARTATE; TRANSFORMING GROWTH FACTOR-BETA-1; MEMBRANE DEPOLARIZATION; PROTOONCOGENE BCL-2; SYMPATHETIC NEURONS; RAT; NEUROTOXICITY; EXPRESSION; INDUCTION; SURVIVAL AB Cerebellar granule neurons can be readily maintained in culture if depolarized with high concentrations of Ki or subtoxic concentrations of various excitatory amino acids. We now report that these depolarizing stimuli promote cerebellar granule neuron survival by blocking their programmed death via apoptosis. Cerebellar granule neurons maintained in depolarizing conditions and then changed to non-depolarizing conditions, exhibit the morphological and biochemical features of apoptosis, including cytoplasmic blebbing, condensation and aggregation of nuclear chromatin and internucleosomal DNA fragmentation. Inhibitors of RNA or protein synthesis greatly attenuate cell death induced by non-depolarizing culture conditions. In contrast, cerebellar granule neurons, when exposed to fresh serum-containing medium or to high concentrations of glutamate, exhibit a delayed-type of neurotoxicity which is non-apoptotic in nature. Given the actions of excitatory amino acid receptor agonists in preventing apoptosis of cultured cerebellar granule neurons, we hypothesize that the functional innervation of postmigratory granule neurons during cerebellar development may prevent further elimination of these neurons by blocking their programmed death. C1 ELI LILLY & CO,LILLY CORP CTR,LILLY RES LABS,INDIANAPOLIS,IN 46285. NIMH,CLIN NEUROSCI BRANCH,MOLEC PHARMACOL SECT,BETHESDA,MD 20892. NINCDS,SURG NEUROL BRANCH,BIOCHEM SECT,BETHESDA,MD 20892. FU FIC NIH HHS [F05-TWO-4591-02] NR 32 TC 176 Z9 205 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 5 PY 1994 VL 656 IS 1 BP 43 EP 51 DI 10.1016/0006-8993(94)91364-1 PG 9 WC Neurosciences SC Neurosciences & Neurology GA PD957 UT WOS:A1994PD95700005 PM 7804844 ER PT J AU CLERICI, M SHEARER, GM AF CLERICI, M SHEARER, GM TI IMMUNOENDOCRINOLOGICAL HYPOTHESIS OF HIV-INFECTION - REPLY SO LANCET LA English DT Letter C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RP CLERICI, M (reprint author), UNIV MILAN,CATTEDRA IMMUNOL,I-20133 MILAN,ITALY. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD SEP 3 PY 1994 VL 344 IS 8923 BP 681 EP 681 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PE386 UT WOS:A1994PE38600037 ER PT J AU SUTRAVE, P SHAFER, BK STRATHERN, JN HUGHES, SH AF SUTRAVE, P SHAFER, BK STRATHERN, JN HUGHES, SH TI ISOLATION, IDENTIFICATION AND CHARACTERIZATION OF THE FUN12 GENE OF SACCHAROMYCES-CEREVISIAE SO GENE LA English DT Note DE CLONING; DNA SEQUENCING; YEAST; GENE EXPRESSION; ESSENTIAL GENE ID CHROMOSOME-I DNA; MOLECULAR-CLONING; REGIONS AB We have cloned and characterized the FUN12 gene which is found on chromosome I of Saccharomyces cerevisiae. The complete nucleotide (nt) sequence of the cDNA and the genomic clones shows that FUN12 is expressed as a 3.7-kb message and should encode a 97 kDa-protein. Immunoprecipitations using antipeptide antibodies showed that the cells contain a Fun12p of this size. The databases contain no nt sequences that are homologous to FUN12 and no protein homologous to Fun12p. Gene disruption experiments showed that FUN12 is an essential gene. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 7 TC 11 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD SEP 2 PY 1994 VL 146 IS 2 BP 209 EP 213 DI 10.1016/0378-1119(94)90294-1 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA PG267 UT WOS:A1994PG26700009 PM 8076820 ER PT J AU MORAWETZ, R MISCHAK, H GOODNIGHT, J LENDENFELD, T MUSHINSKY, JF KUBICEK, CP AF MORAWETZ, R MISCHAK, H GOODNIGHT, J LENDENFELD, T MUSHINSKY, JF KUBICEK, CP TI A PROTEIN KINASE-ENCODING GENE, PKT1, FROM TRICHODERMA-REESEI, HOMOLOGOUS TO THE YEAST YPK1 AND YPK2 (YKR2) GENES SO GENE LA English DT Note DE RECOMBINANT DNA; NUCLEOTIDE SEQUENCE; POLYADENYLATION; PROTEIN KINASE C; SIGNAL TRANSDUCTION; INTRON; FILAMENTOUS FUNGI AB A gene (pkt1) was isolated from the filamentous fungus Trichoderma reesei, which exhibits high homology with the yeast YPK1 and YKR2 (YKR2) genes. It contains a 2123-bp ORF that is interrupted by two introns, and it encodes a 662-amino-acid protein with a calculated M(r) of 72 820. During active growth, pkt1 is expressed as two mRNAs of 3.1 and 2.8 kb which differ in the 3' untranslated region due to the use of two different polyadenylation sites. C1 TECH UNIV VIENNA, INST BIOCHEM TECHNOL & MIKROBIOL, MIKROBIELLE BIOCHEM ABT, A-1060 VIENNA, AUSTRIA. NCI, GENET LAB, MOLEC GENET SECT, BETHESDA, MD 20892 USA. RI Mischak, Harald/E-8685-2011 NR 5 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 EI 1879-0038 J9 GENE JI Gene PD SEP 2 PY 1994 VL 146 IS 2 BP 309 EP 310 DI 10.1016/0378-1119(94)90311-5 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA PG267 UT WOS:A1994PG26700026 PM 8076837 ER PT J AU ERICKSON, JD VAROQUI, H SCHAFER, MKH MODI, W DIEBLER, MF WEIHE, E RAND, J EIDEN, LE BONNER, TI USDIN, TB AF ERICKSON, JD VAROQUI, H SCHAFER, MKH MODI, W DIEBLER, MF WEIHE, E RAND, J EIDEN, LE BONNER, TI USDIN, TB TI FUNCTIONAL IDENTIFICATION OF A VESICULAR ACETYLCHOLINE TRANSPORTER AND ITS EXPRESSION FROM A CHOLINERGIC GENE LOCUS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID ACETYLTRANSFERASE MESSENGER-RNA; VESICLE MONOAMINE TRANSPORTER; INSITU HYBRIDIZATION; PROMOTER REGION; SPINAL-CORD; COMPLETE SEQUENCE; MAMMALIAN-CELLS; RAT; LOCALIZATION; CDNA AB The vesicular acetylcholine transporter (VAChT) has been identified and characterized based on the acquisition of high affinity vesamicol binding and proton-dependent, vesamicol sensitive acetylcholine accumulation by a fibroblast cell line transfected with a clone from a rat pheochromocytoma cDNA library encoding this protein. The distribution of VAChT mRNA coincides with that reported for choline acetyltransferase (ChAT), the enzyme required for acetylcholine biosynthesis, in the peripheral and central cholinergic nervous systems. A human VAChT cDNA was used to localize the VAChT gene to chromosome 10q11.2, which is also the location of the ChAT gene. The entire sequence of the human VAChT cDNA is contained uninterrupted within the first intron of the ChAT gene locus. Transcription of VAChT and ChAT mRNA from the same or contiguous promoters within a single regulatory locus provides a previously undescribed genetic mechanism for coordinate regulation of two proteins whose expression is required to establish a mammalian neuronal phenotype. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. CNRS,NEUROBIOL CELLULAIRE LAB,DEPT NEUROCHIM,F-91190 GIF SUR YVETTE,FRANCE. UNIV MAINZ,DEPT ANAT,W-6500 MAINZ,GERMANY. NCI,FREDERICK CANC RES FACIL,FREDERICK,MD 20797. OKLAHOMA MED RES FDN,PROGRAM MOLEC & CELL BIOL,OKLAHOMA CITY,OK 73104. RP ERICKSON, JD (reprint author), NIMH,MOLEC NEUROSCI SECT,BETHESDA,MD 20892, USA. OI Eiden, Lee/0000-0001-7524-944X FU NIGMS NIH HHS [R01 GM038679] NR 41 TC 320 Z9 326 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 2 PY 1994 VL 269 IS 35 BP 21929 EP 21932 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PE098 UT WOS:A1994PE09800002 PM 8071310 ER PT J AU WONDRAK, EM SAKAGUCHI, K RICE, WG KUN, E KIMMEL, AR LOUIS, JM AF WONDRAK, EM SAKAGUCHI, K RICE, WG KUN, E KIMMEL, AR LOUIS, JM TI REMOVAL OF ZINC IS REQUIRED FOR PROCESSING OF THE MATURE NUCLEOCAPSID PROTEIN OF HUMAN-IMMUNODEFICIENCY-VIRUS, TYPE-1, BY THE VIRAL PROTEASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID MURINE LEUKEMIA-VIRUS; SYNTHETIC PEPTIDE; ESCHERICHIA-COLI; DIMER FORMATION; CIS ELEMENTS; HIV-1; BINDING; RNA; FINGERS; SITE AB In human immunodeficiency virus, RNA selection and packaging during assembly involve the two retroviral-type fingers of the nucleocapsid protein that are held in a constrained configuration by coordinated zinc ions, In this report, we demonstrate that the nucleocapsid protein in a metal bound state is resistant to cleavage by the viral protease, but upon removal of zinc ions by chelating agents, it is hydrolyzed within the first zinc finger between Phe-16 and Asn-17. However, 3-nitrosobenzamide and cupric ions, which release zinc through oxidation of the cysteine residues of the finger, render the nucleocapsid protein resistant to cleavage. Since protease inhibitors and 3-nitrosobenzamide restrict processes relating to steps early in infection, the cleavage of the nucleocapsid protein may represent an essential event that can be exploited for the design of novel antiviral agents. C1 NIDDK,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892. NCI,CELL BIOL LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,ANTIVIRAL DRUG MECHANISMS LAB,FREDERICK,MD 21702. SAN FRANCISCO STATE UNIV,ROMBERG TIBURON CTR,ENVIRONM TOXICOL & CHEM LAB,TIBURON,CA 94920. SAN FRANCISCO STATE UNIV,ROMBERG TIBURON CTR,OCTAMER INC,TIBURON,CA 94920. NR 33 TC 15 Z9 16 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 2 PY 1994 VL 269 IS 35 BP 21948 EP 21950 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PE098 UT WOS:A1994PE09800007 PM 8071314 ER PT J AU OKAJIMA, TIL WIGGERT, B CHADER, GJ PEPPERBERG, DR AF OKAJIMA, TIL WIGGERT, B CHADER, GJ PEPPERBERG, DR TI RETINOID PROCESSING IN RETINAL-PIGMENT EPITHELIUM OF TOAD (BUFO-MARINUS) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ROD OUTER SEGMENTS; ALL-TRANS-RETINOL; BINDING PROTEIN; VITAMIN-A; VISUAL CYCLE; RHODOPSIN; ISOMERIZATION; REGENERATION; SEPARATION AB The formation of 11-cis-[H-3]retinal in the retinal pigment epithelium (RPE) and its release to extracellular medium containing interphotoreceptor retinoid-binding protein (IRBP) were studied in the RPE eyecup of the toad (Bufo marinus). The RPE was labeled with all-trans-[H-3]retinol during an initial 1-h incubation. In phase 2 of the incubation (0-2 h), the extracellular me dium contained initially ligand-free IRBP (0-26 mu M). Retinoids subsequently extracted from the extracellular medium and RPE were analyzed by high performance liquid chromatography and scintillation counting. IRBP increased both the molar amount and specific radioactivity of 11-cis-retinal released by the RPE during phase 2. The molar amount of 11-cis-retinal in the RPE was small relative to that of retinal released with high IRBP. With 21 mu M IRBP and phase 2 incubations of greater than or equal to 10 min, the specific radioactivity of released 11-cis-retinal exceeded that of all-trans retinyl ester in the RPE, The specific radioactivity of 11-cis-retinyl ester was less than that of all-trans-ester, independent of IRBP concentration. The results indicate that IRBP promotes the formation (from all-trans-precursor) as well as the release of 11-cis-retinal and suggest the preferred utilization of recently incorporated and esterified all-trans-retinol in 11-cis-retinal synthesis in a ''last in/first out'' manner. C1 UNIV ILLINOIS,COLL MED,LIONS ILLINOIS EYE RES INST,DEPT OPHTHALMOL & VISUAL SCI,CHICAGO,IL 60612. NEI,BETHESDA,MD 20892. FU NEI NIH HHS [EY-01792, EY-05494] NR 30 TC 34 Z9 34 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 2 PY 1994 VL 269 IS 35 BP 21983 EP 21989 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PE098 UT WOS:A1994PE09800012 PM 8071318 ER PT J AU NEGRE, E VOGEL, T LEVANON, A GUY, R WALSH, TJ ROBERTS, DD AF NEGRE, E VOGEL, T LEVANON, A GUY, R WALSH, TJ ROBERTS, DD TI THE COLLAGEN-BINDING DOMAIN OF FIBRONECTIN CONTAINS A HIGH-AFFINITY BINDING-SITE FOR CANDIDA-ALBICANS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EXTRACELLULAR-MATRIX; COMPLEMENT RECEPTOR; CELL-ADHESION; YEAST-CELLS; ADHERENCE; THROMBOSPONDIN; EXPRESSION; MECHANISMS; INFECTIONS; SURFACES AB A 30-kDa proteolytic fragment from the gelatin/collagen-binding domain of fibronectin is a potent inhibitor of fibronectin binding to Candida albicans, with a molar inhibition constant equal to that of intact fibronectin. Recombinant and proteolytic fragments from the cell-, the fibrin I-, and the heparin II-binding domains also inhibit fibronectin binding, but are 13-1000-fold less active. In suspension, binding of fibronectin to C. albicans is regulated by growth conditions and is specific, saturable, time-dependent, reversible, and divalent cation-independent. Scatchard plot analyses indicate the presence of high affinity (K-d = 1.3 x 10(-9) M) and low affinity (K-d = 1.2 x 10(-7) M) receptors. Recombinant or proteolytic fragments from four binding domains of fibronectin promote adhesion of C. albicans. A recombinant fragment corresponding to the cell-binding domain but with the sequence Arg-Gly-Asp-Ser deleted promotes C. albicans adhesion and inhibits fibronectin binding to C. albicans with the same activity as the natural sequence. Furthermore, four peptides containing the Arg-Gly-Asp sequence and the peptides CS-1 and Arg-Glu-Asp-Val did not block the binding of fibronectin to C. albicans. Thus, in contrast to the specific binding of soluble fibronectin, recognition of immobilized fibronectin by C. albicans is mediated by several domains of the protein. Interactions with the cell-binding domain are not mediated by the Arg-Gly-Asp or other known recognition sequences as it has been suggested. Binding of fibronectin also did not correlate with C(3)d binding to the avirulent clones of C. albicans strain H-12 or with iC(3)b binding to variants of the strain 4918. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. BIOTECHNOL GEN LTD,IL-76326 REHOVOT,ISRAEL. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 41 TC 43 Z9 44 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 2 PY 1994 VL 269 IS 35 BP 22039 EP 22045 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PE098 UT WOS:A1994PE09800020 PM 8071326 ER PT J AU KIHARA, H SIRAGANIAN, RP AF KIHARA, H SIRAGANIAN, RP TI SRC HOMOLOGY-2 DOMAINS OF SYK AND LYN BIND TO TYROSINE-PHOSPHORYLATED SUBUNITS OF THE HIGH-AFFINITY IGE RECEPTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL ANTIGEN RECEPTOR; BASOPHILIC LEUKEMIA-CELLS; T-CELL; SIGNAL TRANSDUCTION; IMMUNOGLOBULIN-E; ZETA-CHAIN; PHOSPHOLIPASE C-GAMMA-1; CYTOPLASMIC DOMAINS; HISTAMINE-RELEASE; BETA-SUBUNIT AB Aggregation of the high affinity IgE receptor (Fc epsilon RI) on rat basophilic leukemia RBL-2H3 cells results in activation of the protein tyrosine kinases Syk and Lyn. Here, we report that fusion proteins containing the Src homology 2 (SH2) domains of Syk and Lyn precipitated tyrosine-phosphorylated proteins from RBL-2H3 cell lysates. There was no detectable precipitation with the N-terminal Syk SH2 domain, minimal with the C-terminal Syk SH2, and strong when the two SH2 domains were expressed in tandem. The Syk SH2 domains showed pronounced selectivity in the binding of tyrosine-phosphorylated proteins. Thus, Syk SH2 precipitated only three phosphoproteins, two of which were the beta and gamma subunits of Fc epsilon RI. In contrast, the fusion protein with Lyn SH2, in addition to precipitating the same Fc epsilon RI components, bound to many other phosphoproteins. Tyrosine phosphorylation of the beta and gamma subunits of Fc epsilon RI was essential for their precipitation with the SH2 fusion proteins. By direct binding studies, there was more binding of Syk SH2 to Fc epsilon RI gamma than to Fc epsilon RI beta, whereas Lyn SH2 bound only to Fc epsilon RI beta. The Syk SH2 fusion protein competitively inhibited the association of gamma and beta with Syk in lysates of activated cells. The SH2-mediated association of these two protein tyrosine kinases with Fc epsilon RI could play an important role in recep tor signaling. RP KIHARA, H (reprint author), NIDR,IMMUNOL LAB,BLDG 10,RM 1N106,BETHESDA,MD 20892, USA. NR 50 TC 179 Z9 179 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 2 PY 1994 VL 269 IS 35 BP 22427 EP 22432 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PE098 UT WOS:A1994PE09800075 PM 8071371 ER PT J AU JUI, HY SUZUKI, Y ACCILI, D TAYLOR, SI AF JUI, HY SUZUKI, Y ACCILI, D TAYLOR, SI TI EXPRESSION OF A CDNA-ENCODING THE HUMAN INSULIN RECEPTOR-RELATED RECEPTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MESSENGER-RNA; I RECEPTOR; GROWTH; KINASE; GENE; LEPRECHAUNISM; SPECIFICITY; MUTATIONS; PATIENT; LIGAND AB The insulin receptor-related receptor (IRR) gene encodes a protein that is homologous to the receptors for insulin and insulin like growth factor-I (IGF-I). We have cloned a full-length cDNA encoding the human IRR by screening a human kidney cDNA library. The nucleotide sequence of our cDNA is identical to the sequence predicted from the human IRR gene except for the presence of an insertion of 24 base pairs between exons 13 and 14. This insertion was caused by use of an alternative splice acceptor site in the 3' portion of intron 13. Interestingly, this alternative splicing occurs at a position at which alternative splicing of the homologous IGF-I receptor mRNA also occurs. We amplified human kidney IRR by the polymerase chain reaction to quantitate the proportion of transcripts which included the 24-nucleotide sequence between exons 13 and 14. Fewer than 10% of the transcripts contained this additional sequence. We expressed the IRR cDNA lacking the 24-base pair insert in NIH-3T3 cells to study the biosynthesis, tyrosine phosphorylation, and ligand binding properties of the IRR. Like receptors for insulin and IGF-I, the IRR was synthesized as a single polypeptide precursor that underwent proteolytic cleavage and glycosylation to yield an a subunit and a p subunit. However, both subunits of the IRR had smaller apparent molecular mass than the homologous subunits of the insulin receptor (108,000 versus 135,000 for the alpha subunits and 66,000 versus 95,000 for the beta subunits). IRR tyrosine phosphorylation could be stimulated by vanadate plus H2O2, which have been demonstrated previously to increase the phosphotyrosine content of the insulin receptor tyrosine kinase. However, proinsulin, insulin, IGF-I, and IGF-II did not stimulate tyrosine phosphorylation of the IRR. We conclude that these peptides are not the ligands for the IRR. C1 NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,DEPT BIOL,BALTIMORE,MD 21218. NR 26 TC 19 Z9 21 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 2 PY 1994 VL 269 IS 35 BP 22446 EP 22452 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PE098 UT WOS:A1994PE09800078 PM 8071374 ER PT J AU MA, Y ITO, Y AF MA, Y ITO, Y TI SEPARATIONS OF BASIC-AMINO-ACID BENZYL-ESTERS BY PH-ZONE-REFINING COUNTERCURRENT CHROMATOGRAPHY SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article AB pH-Zone-refining counter-current chromatography was applied to the separation of basic amino acid benzyl esters. The method uses a retainer base in the stationary phase to retain analytes in the column and an eluent acid to elute the analytes in the decreasing order of pK(a) and hydrophilicity. The preparative capability of the method is demonstrated in the separation of a 10-g quantity of the sample. C1 NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. NR 13 TC 16 Z9 17 U1 1 U2 5 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 SEP 2 PY 1994 VL 678 IS 2 BP 233 EP 240 DI 10.1016/0021-9673(94)80470-2 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PF639 UT WOS:A1994PF63900005 PM 7951985 ER PT J AU CARROLL, FI MASCARELLA, SW KUZEMKO, MA GAO, YG ABRAHAM, P LEWIN, AH BOJA, JW KUHAR, MJ AF CARROLL, FI MASCARELLA, SW KUZEMKO, MA GAO, YG ABRAHAM, P LEWIN, AH BOJA, JW KUHAR, MJ TI SYNTHESIS, LIGAND-BINDING, AND QSAR (COMFA AND CLASSICAL) STUDY OF 3-BETA-(3'-SUBSTITUTED PHENYL), 3-BETA-(4'-SUBSTITUTED PHENYL), AND 3-BETA-(3',4'-DISUBSTITUTED PHENYL)TROPANE-2-BETA-CARBOXYLIC ACID METHYL-ESTERS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CENTRAL NERVOUS-SYSTEM; DOPAMINE UPTAKE SITES; COCAINE RECEPTOR; RAT STRIATUM; TRANSPORTER; ANALOGS; CLONING; INHIBITION; SEROTONIN; NOREPINEPHRINE AB Several new 3 beta-(4'-substituted phenyl)-, 3 beta-(3'-substituted phenyl)-, and 3 beta-(3',4'-disubstituted phenyl)tropane-2 beta-carboxylic acid methyl esters were prepared and assayed for inhibition of [H-3]WIN 35,428 binding to the dopamine transporter. The 3 beta-(3',4'-dichloro) and 3 beta-(4'-chloro-3'-methyl) analogues (2w and 2y; RTI-111 and RTI-112, respectively) with IC50 values of 0.79 and 0.81 nM showed the highest affinity. The contributions of quantitative structure-activity relationship (QSAR) models derived from the classical and comparative molecular field analysis (CoMFA) approaches to rational drug design were examined. CoMFA models were derived using steric and electrostatic potentials with SYBYL default values while the classical models were derived from pi and MR parameters. Using a 12-compound training set, both models were used for predicting the binding affinity of compounds both inside and outside the training set. The CoMFA study provided new insight into the steric and electrostatic factors influencing binding to the DA transporter and provided additional support for our original finding that CoMFA is useful in predicting and designing new compounds for study. The classical QSAR models, which were easier to obtain, suggest that the distribution property (pi) of the compounds is an important factor. Overall, the SAR, CoMFA, and conventional QSAR studies elaborated some features of the cocaine binding site pharmacophore and provided useful predictive information. 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 43 TC 96 Z9 96 U1 4 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD SEP 2 PY 1994 VL 37 IS 18 BP 2865 EP 2873 DI 10.1021/jm00044a007 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA PE834 UT WOS:A1994PE83400008 PM 8071935 ER PT J AU VARMUS, H AF VARMUS, H TI EMBRYO RESEARCH GUIDELINES SO SCIENCE LA English DT Letter RP VARMUS, H (reprint author), NIH,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD SEP 2 PY 1994 VL 265 IS 5177 BP 1345 EP 1345 DI 10.1126/science.8073266 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PE733 UT WOS:A1994PE73300002 PM 8073266 ER PT J AU RABINOVICH, NR MCINNES, P KLEIN, DL HALL, BF AF RABINOVICH, NR MCINNES, P KLEIN, DL HALL, BF TI VACCINE TECHNOLOGIES - VIEW TO THE FUTURE SO SCIENCE LA English DT Article ID ANTIGEN PEPTIDE; IMMUNE-RESPONSES; MOUSE MUSCLE; VIRUS; DNA; IMMUNIZATION; ADJUVANT AB The development of vaccines to prevent infectious diseases has been one of the most important contributions of biomedical science. Recent advances in the basic sciences are now fueling the development of a new generation of vaccines that will be based on rational design approaches. Two factors are making this possible: an improved understanding of the microbial factors required for virulence and the nature of the immune response to infection. The status of new vaccine technologies is summarized here. RP RABINOVICH, NR (reprint author), NIAID,DIV MICROBIOL & INFECT DIS,BETHESDA,MD 20892, USA. NR 36 TC 73 Z9 75 U1 0 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD SEP 2 PY 1994 VL 265 IS 5177 BP 1401 EP 1404 DI 10.1126/science.7521064 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PE733 UT WOS:A1994PE73300036 PM 7521064 ER PT J AU PINN, VW AF PINN, VW TI THE ROLE OF THE NIHS OFFICE-OF-RESEARCH-ON-WOMENS-HEALTH SO ACADEMIC MEDICINE LA English DT Article AB The Office of Research on Women's Health (ORWH) at the National Institutes of Health (NTH) was created in 1990 to carry out three major mandates: (1) to strengthen, develop, and increase research into diseases, disorders, and conditions that are unique to, more prevalent among, or more serious in women, or for which there are different risk factors for women than for men; (2) to ensure that women are appropriately represented in biomedical and biobehavioral research studies, especially clinical trials, that are supported by the NIH; and (3) to direct initiatives to increase the number of women in biomedical careers. One of the ORWH's first accomplishments was a 1992 report that serves as a basis for the ORWH's research agenda; its recommendations focus on scientific issues affecting women's health from birth to old age. To implement these recommendations, the ORWH does not fund studies directly but instead provides funds through NIH institutes and centers to augment new research initiatives, to expand ongoing studies to address high-priority areas concerning women's health (14 of which were identified for special consideration in FY 93), and to increase the participation of women in clinical studies. In addition, the ORWH is playing a key advisory role in the NIH's Women's Health Initiative, a long-term study of over 100,000 women to examine the major causes of death, disability, and frailty-heart disease and stroke, breast and colorectal cancers, and osteoporosis-in older women of all races and from all socioeconomic strata. Also, as part of the NIH's overall effort to include more women and minorities in clinical research, the office formed a task force to address concerns about the recruitment and retention of women in clinical studies and is disseminating information to help investigators to recruit and retain more women as research subjects. The office is also involved in the development of MH guidelines on the participation of women and minorities in clinical research, to be implemented in FY 95. A major goal of the ORWH and the NIH is to promote greater participation of women in biomed-ical research careers; the steps being taken to identify barriers and to increase opportunities are explained. RP PINN, VW (reprint author), NIH,OFF RES WOMENS HLTH,BLDG 1,ROOM 201,BETHESDA,MD 20892, USA. NR 8 TC 24 Z9 24 U1 1 U2 3 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1040-2446 J9 ACAD MED JI Acad. Med. PD SEP PY 1994 VL 69 IS 9 BP 698 EP 702 DI 10.1097/00001888-199409000-00003 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA PG105 UT WOS:A1994PG10500003 PM 8074758 ER PT J AU SHMUELI, U WEISS, GH AF SHMUELI, U WEISS, GH TI EFFECTS OF NONCRYSTALLOGRAPHIC SYMMETRY ON THE SIGMA(1) RELATIONSHIP .1. BICENTRIC ARRANGEMENTS IN P(1)OVER-BAR SO ACTA CRYSTALLOGRAPHICA SECTION A LA English DT Article ID SPACE AB An exact Fourier representation of the probability for the Sigma(1) relationship is derived, which takes into account the presence of noncrystallographic centrosymmetry in the asymmetic unit of the space group P1 $($) over bar$$. Illustrative examples show that the main effect of noncrystallographic symmetry is to decrease the probability that E(2h) is positive, as compared to the corresponding probability in the absence of such symmetry. The effect appears to be more pronounced in the equal-atom case than it is for a structure having a heterogeneous atomic composition. RP SHMUELI, U (reprint author), NIH,DIV COMP RES & TECHNOL,LAB PHYS SCI,BETHESDA,MD 20892, USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0108-7673 J9 ACTA CRYSTALLOGR A JI Acta Crystallogr. Sect. A PD SEP 1 PY 1994 VL 50 BP 605 EP 608 DI 10.1107/S0108767394002400 PN 5 PG 4 WC Chemistry, Multidisciplinary; Crystallography SC Chemistry; Crystallography GA PF501 UT WOS:A1994PF50100009 PM 7946152 ER PT J AU SHRAGER, RI SHMUELI, U WEISS, GH AF SHRAGER, RI SHMUELI, U WEISS, GH TI EXACT CONDITIONAL DISTRIBUTION OF A 3-PHASE INVARIANT IN-SPACE GROUP P1 .4. FURTHER IMPROVEMENTS OF COCHRAN-LIKE APPROXIMATIONS SO ACTA CRYSTALLOGRAPHICA SECTION A LA English DT Article ID 3-PHASE INVARIANT AB A new approximate method of computing the conditional probability density function (c.p.d.f.) of a three-phase invariant is investigated, the results being compared to accurate calculations [Shmueli, Rabinovich and Weiss (1989). Acta Cryst. A45, 361-367]. A direct dependence on N, the number of atoms in the unit cell, is incorporated into the new approximation and its performance in the equal-atom case appears to be excellent over a large range of N values. The polynomial approximation of the recently published method [Posner, Shmueli and Weiss (1993). Acta Cryst. A49, 260-265] has been improved in both accuracy and range. C1 TEL AVIV UNIV,SCH CHEM,IL-69978 TEL AVIV,ISRAEL. RP SHRAGER, RI (reprint author), NIH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20982, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0108-7673 J9 ACTA CRYSTALLOGR A JI Acta Crystallogr. Sect. A PD SEP 1 PY 1994 VL 50 BP 633 EP 636 DI 10.1107/S0108767394002382 PN 5 PG 4 WC Chemistry, Multidisciplinary; Crystallography SC Chemistry; Crystallography GA PF501 UT WOS:A1994PF50100012 PM 7946154 ER PT J AU ZHUANG, ZP ROTH, MJ EMMERTBUCK, MR LUBENSKY, IA LIOTTA, LA SOLOMON, D AF ZHUANG, ZP ROTH, MJ EMMERTBUCK, MR LUBENSKY, IA LIOTTA, LA SOLOMON, D TI DETECTION OF THE VONHIPPEL-LINDAU GENE DELETION IN CYTOLOGIC SPECIMENS USING MICRODISSECTION AND THE POLYMERASE CHAIN-REACTION SO ACTA CYTOLOGICA LA English DT Article DE HIPPEL-LINDAU DISEASE; GENE DELETION; POLYMERASE CHAIN REACTION ID RENAL-CELL CARCINOMA; PCR CONTAMINATION; CHROMOSOME-17; DISEASE; TISSUE; CANCER; LIGHT; DNA; P53 AB Previous studies have demonstrated von Hippel-Lindau (VHL) gene abnormalities in renal cell carcinoma. Archival cytologic samples of renal cell carcinomas (RCCs) from two patients weve evaluated for allelic loss of the VHL gene. Small clusters of renal carcinoma cells were dissected from cytocentrifuge preparations under direct microscopic visualization followed by single-step DNA extraction and subsequent polymerase chain reaction (PCR). Amplification of DNA from the harvested tumor cells demonstrated a loss of heterozygosity at the VHL gene in five RCC specimens obtained from two patients. The combination of microdissection and PCR enabled DNA studies to be performed on a pure population of tumor cells isolated from heterogeneous samples containing admixed normal cellular elements. Selected genetic studies performed on microscopically targeted cells will help to further the biologic and cytomorphologic characterization of the targeted cell population. C1 NCI,DEPT CYTOPATHOL,PATHOL LAB,BETHESDA,MD 20892. NR 23 TC 13 Z9 13 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PD SEP-OCT PY 1994 VL 38 IS 5 BP 671 EP 675 PG 5 WC Pathology SC Pathology GA PH872 UT WOS:A1994PH87200001 PM 8091895 ER PT J AU ALBINI, A FONTANINI, G MASIELLO, L TACCHETTI, C BIGINI, D LUZZI, P NOONAN, DM STETLERSTEVENSON, WG AF ALBINI, A FONTANINI, G MASIELLO, L TACCHETTI, C BIGINI, D LUZZI, P NOONAN, DM STETLERSTEVENSON, WG TI ANGIOGENIC POTENTIAL IN-VIVO BY KAPOSIS-SARCOMA CELL-FREE SUPERNATANTS AND HIV-1 TAT PRODUCT - INHIBITION OF KS-LIKE LESIONS BY TISSUE INHIBITOR OF METALLOPROTEINASE-2 SO AIDS LA English DT Article DE KAPOSIS SARCOMA; HIV; FAT; ANGIOGENESIS; HEPARIN ID TRANSGENIC MICE; AIDS; GROWTH; EXPRESSION; INVITRO; CULTURE; GENE; PROLIFERATION; INVASIVENESS; TIMP-2 AB Objective: To determine the neoplastic nature of Kaposi's sarcoma (KS). A highly vascularized lesion, KS is frequently associated with AIDS, indicating HIV products may be involved. Design and methods: We determined the angiogenic properties of KS cell-secreted products and the HIV-1-tat gene product in vivo. Cell-free secreted products (KS-CM) from cultured epidemic and sporadic KS spindle cells or recombinant (r) HIV-1 tat protein were injected into mice with a matrix support (Matrigel). Results: KS-CM produced lesions carrying all the phenotypic hallmarks of KS, as observed by light and electron microscopy: spindle-shaped cells, haemorrhages and an inflammatory infiltrate, as well as Factor VIII-positive endothelial cells lining new blood vessels. Electron microscopy indicated an initial granulocyte invasion, with spindle-cell migration and neocapillary formation in the centre or the matrix. These lesions required the cofactor heparin; KS-CM or heparin alone were poorly angiogenic. A less intense angiogenesis, with lower cellularity and few granulocytes, was observed in basic fibroblast growth factor (bFGF)/heparin lesions, indicating that factors other than bFGF are present in the KS spindle-cell products. When the collagenase inhibitor tissue inhibitor of metalloproteinases (TIMP)-2 was added to the sponges, KS-CM-induced angiogenesis was reduced by approximately 65% and bFCF-induced angiogenesis inhibited completely. Recombinant HIV-1 tat protein, a growth factor for KS cells, induced vascularization that was also enhanced by heparin, implying that HIV-1 rat could contribute to the aetiology of HIV-associated KS. Conclusions: KS-like lesions were obtained by injecting cell-free secreted products, suggesting that KS is a 'self-propagating' proliferative lesion caused by a cytokine imbalance and not a true neoplasm. Heparin-binding factors appear to be involved, and HIV-1 tar angiogenic properties implicate this molecule in AIDS-associated KS. Inhibition of KS-CM-induced KS-like lesions by TIMP-2 suggests that metalloproteinase inhibitors could be potential therapeutic agents for KS. C1 UNIV PISA,INST PATHOL ANAT,PISA,ITALY. UNIV GENOA,INST ANAT,GENOA,ITALY. NCI,BETHESDA,MD. RP ALBINI, A (reprint author), IST NAZL RIC CANC,DEPT CHEM CARCINOGENESIS,VIALE BENEDETTO 15,10,I-16132 GENOA,ITALY. RI Stetler-Stevenson, William/H-6956-2012; Fontanini, Gabriella/O-7636-2015; Noonan, Douglas/A-8620-2010; OI Stetler-Stevenson, William/0000-0002-5500-5808; Fontanini, Gabriella/0000-0003-1957-2052; Noonan, Douglas/0000-0001-8058-0719; TACCHETTI, CARLO/0000-0003-4602-000X NR 31 TC 139 Z9 140 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD SEP PY 1994 VL 8 IS 9 BP 1237 EP 1244 DI 10.1097/00002030-199409000-00004 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PD647 UT WOS:A1994PD64700004 PM 7528513 ER PT J AU POUTHIER, F PERRIENS, JH MUKADI, Y KAYEMBE, T STLOUIS, ME BROWN, C PRIGNOT, J AF POUTHIER, F PERRIENS, JH MUKADI, Y KAYEMBE, T STLOUIS, ME BROWN, C PRIGNOT, J TI ANTI-A60 IMMUNOGLOBULIN-G IN THE SERODIAGNOSIS OF TUBERCULOSIS IN HIV-SEROPOSITIVE AND SERONEGATIVE PATIENTS SO AIDS LA English DT Note DE HIV INFECTION; TUBERCULOSIS; DIAGNOSIS; SEROLOGY; A60; ENZYME-LINKED IMMUNOSORBENT ASSAY ID IMMUNODEFICIENCY-VIRUS INFECTION; MYCOBACTERIUM-TUBERCULOSIS; PULMONARY TUBERCULOSIS; A60 ANTIGEN; ANTIBODIES; DIAGNOSIS; ELISA; AIDS AB Objective: A60 is a high molecular weight mycobacterial antigen complex. The detection of immunoglobulin (Ig) G antibodies to A60 has been advocated as a reasonably sensitive and specific test for active tuberculosis (TB). We aimed to compare the sensitivity of this test among HIV-seropositive and HIV-seronegative patients with pulmonary TB. Methods: The presence and concentration of anti-A60 IgG antibodies was assessed by enzyme-linked immunosorbent assay in 208 HIV-seropositive and 91 HIV-seronegative Zairian patients with smear-positive pulmonary TB. The relationship between anti-A60 IgG levels and HIV serostatus, CD4+ lymphocyte counts, presence of clinical AIDS, and tuberculin skin test results was verified. Results: Only 36.5% of the HIV-seropositive, compared with 69.2% of the HIV-seronegative patients had a positive anti-A60 IgG test (P <0.00001). Among HIV-seropositive patients, anti-A60 Ige levels did not differ according to CD4+ lymphocyte counts, presence of clinical AIDS, or tuberculin skin test results. Conclusions: Among patients with pulmonary TB, the sensitivity of testing for anti-A60 IgG was much lower among HIV-seropositive than among HIV-seronegative patients, even from the early stages of HIV-related immunodeficiency. This limits the utility of anti-A60 IgG-antibody testing in the diagnosis of TB among HIV-infected patients. C1 PROJET SIDA,KINSHASA,ZAIRE. INST TROP MED,ANTWERP,BELGIUM. BELGIAN AGCY DEV & COOPERAT,BRUSSELS,BELGIUM. CTR DIS CONTROL & PREVENT,DIV HIV AIDS,ATLANTA,GA. NIAID,BETHESDA,MD. RP POUTHIER, F (reprint author), UNIV CATHOLIQUE LOUVAIN,CLIN UNIV MT GODINNE,DEPT BIOL CLIN,B-5530 YVOIR,BELGIUM. NR 19 TC 8 Z9 8 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD SEP PY 1994 VL 8 IS 9 BP 1277 EP 1280 DI 10.1097/00002030-199409000-00009 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PD647 UT WOS:A1994PD64700009 PM 7802980 ER PT J AU LANE, HC AF LANE, HC TI INTERFERONS IN HIV AND RELATED DISEASES SO AIDS LA English DT Article; Proceedings Paper CT Into the Future - HIV Therapy Advances, Satellite Symposium to the 4th European Conference on Clinical Aspects of Treatment of HIV Infection CY MAR 16, 1994 CL MILAN, ITALY DE INTERFERON-ALPHA; KAPOSIS SARCOMA; HEPATITIS B; HEPATITIS C ID IMMUNODEFICIENCY-VIRUS HIV; PLACEBO-CONTROLLED TRIAL; RECOMBINANT INTERFERON; KAPOSIS SARCOMA; THROMBOCYTOPENIC PURPURA; SYNERGISTIC INHIBITION; VIRAL-HEPATITIS; SYNDROME AIDS; ALPHA-A; ZIDOVUDINE AB Background: Since interferon-alpha has a very broad spectrum of activity it has been investigated in several clinical settings in the HIV-infected population. Kaposi's sarcoma: The rate of response to interferon-alpha is low in patients with low CD4 cell counts, but response rates of over 45% have been achieved in patients with higher counts. Primary therapy in HIV infection: In 34 asymptomatic patients, the overall percentage of CD4 cells was higher in patients taking interferon-alpha compared to those taking a placebo and the rate of opportunistic infections was lower after a long-term follow-up. A relatively high dose of interferon-alpha was associated with predictable side effects. Lower doses have been used in combination with zidovudine. In a recent trial, 180 patients took either zidovudine alone, interferon-alpha alone or both drugs in combination. So far, the CD4 cell counts have been similar in all treatment groups. Hepatitis infection: The rate of response shown by hepatitis B infection to interferon-alpha in patients with both hepatitis B and HIV has been reported as less than that in patients without HIV infection. Overall, studies have shown that approximately 37% of patients are cleared of hepatitis B DNA with 3 months of interferon-alpha treatment, compared with a 17% rate of spontaneous clearance. Among hepatitis C patients, 50-75% show a reduction in serum transaminases with 3 months of treatment. Conclusions: Interferon-alpha is of benefit in some HIV-infected patients, demonstrating efficacy in Kaposi's sarcoma, hepatitis B and hepatitis C. RP LANE, HC (reprint author), NIAID,9000 ROCKVILLE PIKE,BLDG 10,ROOM 115231,BETHESDA,MD 20892, USA. NR 20 TC 11 Z9 13 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD SEP PY 1994 VL 8 SU 3 BP S19 EP S23 DI 10.1097/00002030-199409001-00005 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PQ108 UT WOS:A1994PQ10800005 PM 7840912 ER PT J AU FRANCHINI, G REITZ, MS AF FRANCHINI, G REITZ, MS TI 10TH ANNIVERSARY PERSPECTIVES ON AIDS - PHYLOGENESIS AND GENETIC COMPLEXITY OF THE NONHUMAN PRIMATE RETROVIRIDAE SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Review ID T-CELL LEUKEMIA; VIRUS TYPE-I; SIMIAN IMMUNODEFICIENCY VIRUS; AFRICAN-GREEN MONKEYS; HUMAN FOAMY VIRUS; PAPUA-NEW-GUINEA; HUMAN LYMPHOTROPIC RETROVIRUSES; VIRION-ASSOCIATED PROTEIN; CHRONIC FATIGUE SYNDROME; SURFACE CD4 EXPRESSION AB The three known groups of nonhuman primate retroviruses (simian immunodeficiency virus, sinian T cell lymphotrop/leukemic virus type I, and simian foamy virus) are thought to have equivalent human counterparts. This is clearly the case with human immunodeficiency virus types 1 and 2, the causative agents of acquired immunodeficiency syndrome, and with human T cell lymphotropic/leukemia virus type I(HTLV-I), which causes T cell leukemia and a progressive form of myelopathy (tropical spastic paraparesis/HTLV-I-associated myelopathy), and HTLV-II. However, the presence of spunaviruses (foamy viruses) in humans remains uncertain. Data accumulated in the last 5 years suggest the possibility that the human retroviruses are indeed the result of transmission of simian retroviruses to humans. In this article we attempt to parallel the genetic features of the simian retroviridae with their human counterparts and argue for the possibility of horizontal transmission of these viruses from monkeys to humans. RP FRANCHINI, G (reprint author), NCI,TUMOR CELL BIOL LAB,BLDG 37,ROOM 6A09,BETHESDA,MD 20892, USA. NR 221 TC 26 Z9 26 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 SEP PY 1994 VL 10 IS 9 BP 1047 EP 1060 DI 10.1089/aid.1994.10.1047 PG 14 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PL598 UT WOS:A1994PL59800001 PM 7826692 ER PT J AU BERMAS, BL PETRI, M BERZOFSKY, JA WAISMAN, A SHEARER, GM MOZES, E AF BERMAS, BL PETRI, M BERZOFSKY, JA WAISMAN, A SHEARER, GM MOZES, E TI BINDING OF GLYCOPROTEIN-120 AND PEPTIDES FROM THE HIV-1 ENVELOPE BY AUTOANTIBODIES IN MICE WITH EXPERIMENTALLY-INDUCED SYSTEMIC LUPUS-ERYTHEMATOSUS AND IN PATIENTS WITH THE DISEASE SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTI-DNA IDIOTYPE; ANTIBODIES; INFECTION; INDUCTION; AIDS; IMMUNOREGULATION; IDENTIFICATION; AUTOIMMUNITY; MODEL AB Systemic lupus erythematosus (SLE) and infection with the human immunodeficiency virus type 1 (HIV) are diseases that are characterized by immune dysregulation and autoantibody production. In this article we identify and characterize IgG antibodies from mice with SLE and SLE patients that bind HIV gp120 and HIV envelope-derived peptides. SLE can be induced in susceptible mouse strains by immunization with a human monoclonal anti-DNA antibody that bears a common idiotype designated 16/6 Id. We tested sera from various strains of mice in which experimental SLE was induced by this method, as well as from 93 patients with SLE and 31 controls (17 healthy controls, 14 patients with other autoimmune diseases) for the presence of antibodies reactive to gp120 by an ELISA. Antibodies reactive with gp120 were produced by BALB/c, C3H.SW, AKR, and DBA/2 mice, all of which were 16/6 Id immunized and had experimental SLE. C57BL/6 mice, which are resistant to induction of SLE by this method, did not produce antibodies reactive with gp120 despite 16/6 immunization. Forty-three percent of SLE patients made antibodies that bound to gp120 at titers greater than 1:40, whereas 12% of healthy control sera (p less than or equal to 0.02) and 14% of patients with other autoimmune diseases contained such antibodies (p less than or equal to 0.05). We delineated the specificity of this antibody activity by testing far reactivity to six HIV envelope peptides. In both mice and SLE patients, sera reactive with gp120 recognized the same three envelope peptides. Removal of the anti-DNA antibodies from the sera by DNA-agarose affinity purification did not change anti-gp120 specificity. We conclude that sera from mice with experimentally induced SLE and patients with SLE produce antibodies that recognize certain epitopes defined by gp120, including specific epitopes contained in the HIV envelope. Antibodies recognizing gp120 constitute a distinct population when compared to anti-DNA antibodies. These results raise the possibility that common immune dysregulatory signals are activated after HIV infection and in the development of lupus. C1 NCI, EXPTL IMMUNOL BRANCH, BETHESDA, MD 20892 USA. JOHNS HOPKINS UNIV, CTR MED, BALTIMORE, MD 21205 USA. NCI, METAB BRANCH, BETHESDA, MD 20892 USA. WEIZMANN INST SCI, DEPT CHEM IMMUNOL, IL-76100 REHOVOT, ISRAEL. RI Waisman, Ari/C-7383-2015 OI Waisman, Ari/0000-0003-4304-8234 FU NHLBI NIH HHS [HL 47080-01] NR 37 TC 27 Z9 28 U1 1 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 SEP PY 1994 VL 10 IS 9 BP 1071 EP 1077 DI 10.1089/aid.1994.10.1071 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PL598 UT WOS:A1994PL59800004 PM 7826694 ER PT J AU GOEDERT, JJ DUBLIN, S AF GOEDERT, JJ DUBLIN, S TI PERINATAL TRANSMISSION OF HIV TYPE-1 - ASSOCIATIONS WITH MATERNAL ANTI-HIV SEROLOGICAL REACTIVITY SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NEUTRALIZING ANTIBODIES; VERTICAL TRANSMISSION; MONOCLONAL-ANTIBODIES; SYNTHETIC PEPTIDES; HIGH-RISK; ENVELOPE; GP120; INFECTION; WOMEN AB As a hypothesis-generating study of large regions of the human immunodeficiency virus type 1 (HIV-1) envelope, we collaborated with several laboratories to test sera from subgroups of 65 HIV-1-positive pregnant women, 18 (28%) of whom transmitted the virus to their infants. Assays included neutralizing antibodies to HIVLAI and reactivity to 102 HIV-1 Env peptides with sequences based on strains LAI, MN, SC, RF, and WMJ-2 as well as several clinical isolates, spanning about 65% of gp120 and about 80% of gp41. Results for the V3 loop and for neutralizing activity were conflicting and for the most part did not reach statistical significance. Transmission risk appeared lower with reactivity to a few gp41 epitopes (amino acids 571-585, 736-750, and perhaps 650-663), whereas risk appeared higher with reactivity to two gp120 epitopes (amino acids 466-480 and 475-486) and one gp41 epitope (amino acids 547-576). However, these associations could have occurred simply by chance because such a large number of peptides was tested. With independently synthesized peptides, results between laboratories often were inconsistent. However, reproducibility was good (rank correlation coefficient greater than or equal to 0.78) when the same protocols and peptides were used. Although this study could not identify a humoral immune response to linear Env peptides that consistently and broadly protected against perinatal transmission of HIV-1, there were regions of gp120 and gp41 that should be evaluated in larger cohorts and with techniques to investigate potential conformational epitopes and neutralization to autologous or clinical isolates of HIV-1 from the community. RP GOEDERT, JJ (reprint author), NCI,VIRAL EPIDEMIOL BRANCH,ROCKVILLE,MD 20852, USA. FU NCI NIH HHS [N01-CP-61013]; NICHD NIH HHS [N01-HD-82913, R01-HD-25714] NR 58 TC 9 Z9 9 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD SEP PY 1994 VL 10 IS 9 BP 1125 EP 1134 DI 10.1089/aid.1994.10.1125 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PL598 UT WOS:A1994PL59800010 PM 7530026 ER PT J AU REITZ, MS HALL, L ROBERTGUROFF, M LAUTENBERGER, J HAHN, BM SHAW, GM KONG, LI WEISS, SH WATERS, D GALLO, RC BLATTNER, W AF REITZ, MS HALL, L ROBERTGUROFF, M LAUTENBERGER, J HAHN, BM SHAW, GM KONG, LI WEISS, SH WATERS, D GALLO, RC BLATTNER, W TI VIRAL VARIABILITY AND SERUM ANTIBODY-RESPONSE IN A LABORATORY WORKER INFECTED WITH HIV TYPE-1 (HTLV TYPE IIIB) SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NEUTRALIZING MONOCLONAL-ANTIBODY; NUCLEOTIDE-SEQUENCE ANALYSIS; ENVELOPE GENE; POINT MUTATION; AIDS VIRUS; GENOMIC DIVERSITY; VARIABLE REGIONS; SELECTION; EPITOPE AB Molecular clones of HIV-1 were obtained from isolates cultured from peripheral blood mononuclear cells (PBMCs) and directly from uncultured PBMCs from a laboratory worker accidentally infected with the HIV-1 laboratory strain, HIV-1(HTLV-IIIB). Envelope sequences corresponding to the first 752 amino acids of HIV-1(HTLV-IIIB) clone BH10 were obtained from clones of cultured virus and sequenced. Three env clones obtained shortly after infection differed among themselves at only seven nucleotide positions, resulting in one amino acid substitution and one frameshift mutation. These envelope sequences were as similar to the envelope sequences of various IIIB clones as the latter were to each other. env divergence increased over the course of infection. However, the overall diversity in env clones obtained two or more years after infection was still comparable to that among IIIB env clones from the original IIIB culture. Multiple clones of partial env gene sequences containing the V3 loop were also obtained directly from uncultured PBMCs by polymerase chain reaction amplification. The env sequences of these clones were generally similar to those of the cultured viruses. Within the V3 region, the earliest isolates retained the sequence of the HXB2 clone from IIIB. Clones obtained later showed a progressive divergence in V3. An A-to-T substitution within the GPGRAF sequence at the tip of the V3 loop was observed within 1 year after infection, and this mutation predominated in all subsequent isolates. Antibodies against the V3 loops of IIIB and divergent 1987 and 1990 LW isolates appeared simultaneously in laboratory worker serum and persisted with no significant differences in titer. Furthermore, neutralization studies with autologous sequential sera suggested selection for the A-to-T change in V3 was not due to V3-directed antibodies. These results demonstrate a surprising homogeneity among env sequences of HIV-1 from an infected laboratory worker, perhaps because the initial infection originated from a relatively homogeneous population of tissue culture-adapted virus. C1 NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT MICROBIOL,BIRMINGHAM,AL 35294. NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,AIDS VACCINE PROGRAM,FREDERICK,MD 21702. RP REITZ, MS (reprint author), NCI,TUMOR CELL BIOL LAB,BLDG 37,ROOM 6A09,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 46 TC 25 Z9 32 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD SEP PY 1994 VL 10 IS 9 BP 1143 EP 1155 DI 10.1089/aid.1994.10.1143 PG 13 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PL598 UT WOS:A1994PL59800012 PM 7826699 ER PT J AU BLACK, FL BIGGAR, RJ NEEL, JV MALONEY, EM WATERS, DJ AF BLACK, FL BIGGAR, RJ NEEL, JV MALONEY, EM WATERS, DJ TI ENDEMIC TRANSMISSION OF HTLV TYPE-II AMONG KAYAPO INDIANS OF BRAZIL SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID VIRUS TYPE-I; INFECTION; SEROPREVALENCE; AMERINDIANS AB Serological studies on 926 blood samples from 703 Brazilian Kayapo (Cayapo) Indians showed, by conventional definition of HTLV seropositivity, a 28% prevalence of human T lymphotropic virus (HTLV) infection, the highest yet reported. Immunoblot (WB) and SYNTH-EIA patterns indicate that the predominant infecting agent is type II. Of children under 15 years old, 12% were positive, and of persons over 60; more than 60%. Perinatal and heterosexual modes of transmission offer an adequate explanation of this incidence. Infection in infancy may include infection via breast milk from women other than the mother. Evidence of new infection in adults is apparent at an earlier age in women than in men. This pattern of antibody prevalence was not determined by cohort effects, as demonstrated by tests of serial specimens. Enzyme immunosorbent assay (EIA) absorbencies were not stable in the paired specimens: five serum pairs reverted and mean absorbencies declined over some age ranges. Many specimens with relatively high, but less than positive, EIA results were positive by immunoblot (WB). This suggests that the standard EIA end point does not identify all infected persons. If the WB alone indicates positivity, 47% of the whole population, and more than 80% of the older age groups, are infected with HTLV-II. C1 NCI,VIRAL EPIDEMIOL BRANCH,ROCKVILLE,MD 20850. UNIV MICHIGAN,SCH MED,DEPT HUMAN GENET,ANN ARBOR,MI 48104. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,FREDERICK,MD 21701. RP BLACK, FL (reprint author), YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,333 CEDAR ST,NEW HAVEN,CT 06520, USA. NR 36 TC 41 Z9 44 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD SEP PY 1994 VL 10 IS 9 BP 1165 EP 1171 DI 10.1089/aid.1994.10.1165 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PL598 UT WOS:A1994PL59800014 PM 7826700 ER PT J AU LAUER, MS ANDERSON, KM LARSON, MG LEVY, D AF LAUER, MS ANDERSON, KM LARSON, MG LEVY, D TI A NEW METHOD FOR INDEXING LEFT-VENTRICULAR MASS FOR DIFFERENCES IN BODY-SIZE SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY HEART-DISEASE; ADULTS; ECHOCARDIOGRAPHY; HYPERTROPHY; GEOMETRY; CHILDREN; IMPACT AB Left ventricular (LV) mass is determined to a large extent by body size. This has created controversy regarding the optimal method of defining normal values in the clinical setting. Previous groups have advocated indexing LV mass for body surface area, lean body mass, or height, which is an obesity-independent measure of body size. This study describes a new approach that involves dividing LV mass by height raised to a noninteger power. In a sample of 387 men and 714 women who were between 20 and 45 years of age and who were free of cardiovascular disease, the height exponent was determined by logarithmic regression models to be 2.12 in men and 1.91 in women; in a pooled analysis, the height exponent was 1.97. This approach reduced male versus female differences in the mean and 95th percentile values for LV mass; mean value differences were reduced from 52% among raw values to 29% among adjusted values. Compared with height or body surface area indexation, it was found to slightly increase the correlation between LV mass and systolic blood pressure. In contrast body surface area indexation reduced the association between LV mass and obesity. The current method of indexation is independent of obesity, reduces LV mass variability associated with body size and gender, and may therefore be a useful method for defining normal and abnormal values of LV mass in the clinical setting. The findings of this study also suggest that indexation of LV mass for body surface area is inappropriate. C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA 01701. CLEVELAND CLIN FDN,DEPT CARDIOL,CLEVELAND,OH 44195. NHLBI,BETHESDA,MD 20892. RI Lauer, Michael/L-9656-2013 OI Lauer, Michael/0000-0002-9217-8177 NR 26 TC 113 Z9 114 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 1 PY 1994 VL 74 IS 5 BP 487 EP 491 DI 10.1016/0002-9149(94)90909-1 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PD588 UT WOS:A1994PD58800015 PM 8059731 ER PT J AU RODRIGUEZ, BL MASAKI, K BURCHFIEL, C CURB, JD FONG, KO CHYOU, PH MARCUS, EB AF RODRIGUEZ, BL MASAKI, K BURCHFIEL, C CURB, JD FONG, KO CHYOU, PH MARCUS, EB TI PULMONARY-FUNCTION DECLINE AND 17-YEAR TOTAL MORTALITY - THE HONOLULU HEART PROGRAM SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE ASIAN AMERICANS; FORCED EXPIRATORY VOLUME; LUNG; MORTALITY; RESPIRATION; SMOKING ID FORCED EXPIRATORY VOLUME; RESPIRATORY SYMPTOMS; CARDIOVASCULAR-DISEASE; RISK FACTOR; ONE 2ND; MEN; POPULATION; ASCERTAINMENT; PREDICTORS; FRAMINGHAM AB The Honolulu Heart Program continues to follow a cohort of Japanese-American men initially aged 45-68 years, of whom 4,000 had three acceptable measurements of forced expiratory volume in 1 second (FEV(1)) between 1965 and 1974 and were free of cardiovascular disease and cancer. The 6-year rate of change (slope) in FEV(1) was calculated using a within-person linear regression method. Men were divided into tertiles based on the rate of change in FEV(1). During 17 subsequent years of follow-up, 796 deaths occurred. The tertile with the greatest rate of decline in FEV(1) (mean, -61 ml/year) had the highest age-adjusted total mortality rate (17.3/1,000 person-years), followed by rates of 13.2 for the middle tertile (mean, -25 ml/year) and 11.0 for men with the smallest change in FEV(1) (mean, +9 ml/year) (test for trend, p < 0.0001). Using the Cox model, comparing the tertile with the smallest change in FEV(1) as a reference group with the tertile with the greatest decline in FEV(1), and after adjusting for age, hypertension, smoking, body mass index, alcohol intake, diabetes mellitus, and cholesterol, the authors found the relative risk (RR) for total mortality to be 1.48 (95% confidence interval (CI) 1.24-1.77). After stratification by smoking status, this association remained significant for past smokers (RR = 1.79, 95% CI 1.31-2.14), as well as for the low, less than or equal to 42 (RR = 1.46, 95% CI 1.05-2.03), and high, >42 (RR = 1.56, 95% CI 1.20-2.02), pack-year groups. An increased risk was also present for current smokers (RR = 1.29), but it was of borderline significance (p = 0.08). No association was found among never smokers. These data suggest that the rate of decline in FEV(1) is a predictor of total mortality among smokers. C1 UNIV HAWAII MANOA,JOHN A BURNS SCH MED,HONOLULU,HI 96822. NHLBI,HONOLULU HEART PROGRAM,HONOLULU,HI. RP RODRIGUEZ, BL (reprint author), KUAKINI MED CTR,HONOLULU HEART PROGRAM,347 N KUAKINI ST,HONOLULU,HI 96817, USA. FU NHLBI NIH HHS [N01-HC-05102] NR 24 TC 44 Z9 45 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 1 PY 1994 VL 140 IS 5 BP 398 EP 408 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PE354 UT WOS:A1994PE35400002 PM 8067332 ER PT J AU KOVELESKY, RA MINOR, JR AF KOVELESKY, RA MINOR, JR TI ANTIRETROVIRAL THERAPY DURING PREGNANCY SO AMERICAN JOURNAL OF HOSPITAL PHARMACY LA English DT Note ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN PLACENTA; ZIDOVUDINE; WOMEN; INFECTION C1 NIAID,CTR CLIN,DEPT PHARM,INTRAMURAL AIDS RES PROGRAM,BETHESDA,MD 20892. NR 11 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 0002-9289 J9 AM J HOSP PHARM JI Am. J. Hosp. Pharm. PD SEP 1 PY 1994 VL 51 IS 17 BP 2187 EP 2189 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PE151 UT WOS:A1994PE15100019 PM 7985701 ER PT J AU CARMELLI, D CARDON, LR FABSITZ, R AF CARMELLI, D CARDON, LR FABSITZ, R TI CLUSTERING OF HYPERTENSION, DIABETES, AND OBESITY IN ADULT MALE TWINS - SAME GENES OR SAME ENVIRONMENTS SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID FAMILIAL DYSLIPIDEMIC HYPERTENSION; CORONARY HEART-DISEASE; INSULIN RESISTANCE; RISK-FACTORS; CARDIOVASCULAR RISK; GLUCOSE-INTOLERANCE; ADIPOSE-TISSUE; BODY-FAT; CONCORDANCE; METABOLISM AB We investigated the mediating role of genetic factors in the clustering of hypertension, diabetes, and obesity, using the twin registry maintained by the National Academy of Sciences-National Research Council. The study sample included 2,508 male twin pairs born between 1917 and 1927 who responded to a mailed questionnaire that covered demographic variables, cardiovascular risk factors, and health behaviors. The incidence of hypertension and diabetes in this cohort was ascertained from subjects' self-report of a physician diagnosis and/or the use of prescription medications. The body-mass index calculated from self-reports of height and weight was used as a measure of obesity. Descriptive analyses indicated probandwise concordance rates of 34.0%, 31.2%, and 32.7%, respectively, for the joint occurrences of hypertension and diabetes, hypertension and obesity, and diabetes and obesity in MZ twin pairs. Corresponding concordance rates in DZ twin pairs were 8.1%, 14.9%, and 2.8%. The probandwise concordance for the clustering of all three conditions in the same individuals was 31.6% in MZ pairs and 6.3% in DZ pairs (relative risk 5.0; chi(2)(1)=2.6; P<.15). Multivariate genetic modeling of the correlation in liabilities to develop these conditions suggested the presence of a common latent factor mediating the clustering of hypertension, diabetes, and obesity in this twin sample. This common factor was influenced by both genetic and environmental effects (59% genetic, 41% environmental). The genetic influences on the common latent factor were due to dominant rather than additive sources; the environmental influences appeared to be specific rather than shared by co-twins. C1 NHLBI,BETHESDA,MD 20892. RP CARMELLI, D (reprint author), SRI INT,HLTH SCI PROGRAM,333 RAVENSWOOD AVE,MENLO PK,CA 94025, USA. FU NHLBI NIH HHS [HL 46115]; NIAAA NIH HHS [ADAMHA AA08925] NR 37 TC 146 Z9 153 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP PY 1994 VL 55 IS 3 BP 566 EP 573 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA PF509 UT WOS:A1994PF50900018 PM 8079995 ER PT J AU STEWART, WF STEWART, PA AF STEWART, WF STEWART, PA TI OCCUPATIONAL CASE-CONTROL STUDIES .1. COLLECTING INFORMATION ON WORK HISTORIES AND WORK-RELATED EXPOSURES SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE OCCUPATIONAL EPIDEMIOLOGY; CASE-CONTROL STUDIES; EXPOSURE ASSESSMENT; INDUSTRIAL HYGIENE PRINCIPLES ID VALIDITY; MEMORY; INTERVIEW; RISK AB The strength and credibility of evidence from occupational case-control studies largely depend on the validity and precision with which the work history is reported and the exposure is assessed. We discuss the two steps which ultimately lead to an exposure decision. The first step involves the exchange between the respondent and an interviewer. The latter is usually naive to occupations and workplace exposures and, as such, is limited to asking generic and open-ended questions about the workplace. Often, this type of information is too nonspecific to assess exposure. In the second step, an expert reviews the information reported on each occupation and decides on exposure status without contacting either the interviewer or respondent. Exposure assessment is not, therefore, integrated with data collection and, in fact, is usually not initiated until after all the interviews are completed. As such, the exposure expert does not have an opportunity to resolve questions before making the exposure decision. To improve the quality and specificity of data collected, we have developed over 40 sets of close-ended questions (branch questions) which are specific to defined occupations. These branch questions, incorporated into a computer-assisted telephone interview, are asked if selected occupations or their synonyms are reported. Second, to link the data collection process with the assessment process, we have developed a procedure called SCORE (Subject Corrected Occupational Report) which provides the industrial hygienist with a cost efficient method to ask questions directly of respondents. Shortly after each interview is completed, a computerized version of the work history is reviewed by the industrial hygienist who develops questions when more information is needed. Subsequently, respondents are mailed a form listing their reported work history along with the questions. After two mailings, 73% of participants in a pilot study returned the SCORE form. (C) 1994 Wiley-Liss, Inc. C1 NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. RP STEWART, WF (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,615 N WOLFE ST,BALTIMORE,MD 21205, USA. NR 25 TC 75 Z9 75 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 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD SEP PY 1994 VL 26 IS 3 BP 297 EP 312 DI 10.1002/ajim.4700260304 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PD297 UT WOS:A1994PD29700003 PM 7977404 ER PT J AU STEWART, PA STEWART, WF AF STEWART, PA STEWART, WF TI OCCUPATIONAL CASE-CONTROL STUDIES .2. RECOMMENDATIONS FOR EXPOSURE ASSESSMENT SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE EXPOSURE ASSESSMENT; CASE-CONTROL STUDIES; OCCUPATIONAL EPIDEMIOLOGY; INDUSTRIAL HYGIENE PRINCIPLES ID LEAD-EXPOSURE; HISTORIES; INDUSTRY; RISK AB Obtaining valid and reliable quantitative exposure estimates is a significant challenge in community-based case-control studies in part, because industrial hygiene monitoring data are usually not available and detailed information on the job and work environment is usually not systematically obtained or assessed. To improve the quality and credibility of disease risk information obtained from occupational case-control studies, we recommend that standardized exposure assessment methods be used to derive quantitative exposure estimates. We identify sources of variation inherent to the assessment process, including: the quality of the information reported on the job, industry, activities, and materials; the industrial hygienist's familiarity with the reported job/industry; the probability that the job/industry was exposed, which depends on plant preferences for particular substances, on process technology, and on customer specifications; and variability in workplace characteristics. To improve the reliability of estimating job-related exposures both within and between studies, we recommend that the epidemiologic analyses be conducted with and without data rated to be of poor quality; that contact be made with experts when the study industrial hygienist is unfamiliar with the manufacturing process in question; that existing data bases be used to estimate the probability of exposure; that a data base be developed that describes manufacturing processes; and that explicit criteria based on industrial hygiene principles be used to evaluate workplace characteristics. In addition, a procedure is described for deriving quantitative exposure estimates by using a reference scale of frequently monitored jobs with their associated mean exposure levels. Areas of research are identified to improve exposure assessment in community-based case-control studies. (C) 1994 Wiley-Liss, Inc. C1 JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. RP STEWART, PA (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EPN 418,BETHESDA,MD 20892, USA. NR 38 TC 60 Z9 60 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 SEP PY 1994 VL 26 IS 3 BP 313 EP 326 DI 10.1002/ajim.4700260305 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PD297 UT WOS:A1994PD29700004 PM 7977405 ER PT J AU YIN, SN LINET, MS HAYES, RB LI, GL DOSEMECI, M WANG, YZ CHOW, WH JIANG, ZL WACHOLDER, S ZHANG, WU DAI, TR CHAO, XJ ZHANG, XC YE, PZ KOU, QR MENG, JF ZHO, JS LIN, XF DING, CY KNELLER, R BLOT, WJ AF YIN, SN LINET, MS HAYES, RB LI, GL DOSEMECI, M WANG, YZ CHOW, WH JIANG, ZL WACHOLDER, S ZHANG, WU DAI, TR CHAO, XJ ZHANG, XC YE, PZ KOU, QR MENG, JF ZHO, JS LIN, XF DING, CY KNELLER, R BLOT, WJ TI COHORT STUDY AMONG WORKERS EXPOSED TO BENZENE IN CHINA .1. GENERAL-METHODS AND RESOURCES SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE BENZENE; OCCUPATIONAL EXPOSURE; LEUKEMIA; HEMATOPOIETIC NEOPLASMS; CANCER ID OCCUPATIONAL EXPOSURE; CANCER MORTALITY; RISK ASSESSMENT; RUBBER INDUSTRY; LEUKEMIA; MALIGNANCIES; EMPLOYEES; TURKEY AB Benzene is recognized internationally as a leukemogen, but the available data to clarify dose-response relationships and examine risks of malignancies other than leukemia are sparse. A collaborative study was therefore carried out to expand on a previous retrospective cohort mortality study of Chinese benzene-exposed workers. Methods and resources used in the 16-year follow-up of 74,828 benzene-exposed and 35,805 unexposed workers employed for any length of time during 1972-1987 in 712 factories in 12 cities in China are described. Details are provided of the study organization, assessment of benzene exposures since 1949, characterization of factories and workers by exposure status, city, and sex, identification and confirmation of cancers and other deaths, and quality control procedures. The distinguishing features of the study are discussed in relation to earlier cohort studies, and study limitations as well as strengths are presented. (C) 1994 Wiley-Liss, Inc. C1 NCI, EPIDEMIOL & BIOSTAT PROGRAM, EPN 415, ROCKVILLE, MD 20892 USA. CHINESE ACAD PREVENT MED, INST OCCUPAT MED, BEIJING, PEOPLES R CHINA. STN PUBL HLTH & PREVENT INFECT, SHANGHAI, PEOPLES R CHINA. STN PUBL HLTH & PREVENT INFECT, CHENGDU, PEOPLES R CHINA. STN PUBL HLTH & PREVENT INFECT, CHONGQING, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, TIANJIN, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, HENAN, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, HEILONGJIANG, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, SHENYANG, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT BIS, JIANGXI, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, NANCHANG, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, GUANGZHO, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, JINZHOU, PEOPLES R CHINA. FU NCI NIH HHS [N01-CP-85841, N01-CP-71119] NR 43 TC 31 Z9 32 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0271-3586 EI 1097-0274 J9 AM J IND MED JI Am. J. Ind. Med. PD SEP PY 1994 VL 26 IS 3 BP 383 EP 400 DI 10.1002/ajim.4700260312 PG 18 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PD297 UT WOS:A1994PD29700011 PM 7977412 ER PT J AU DOSEMECI, M LI, GL HAYES, RB YIN, SN LINET, M CHOW, WH WANG, YZ JIANG, ZL DAI, TR ZHANG, WU CHAO, XJ YE, PZ KOU, QR FAN, YH ZHANG, XC LIN, XF MENG, JF ZHO, JS WACHOLDER, S KNELLER, R BLOT, WJ AF DOSEMECI, M LI, GL HAYES, RB YIN, SN LINET, M CHOW, WH WANG, YZ JIANG, ZL DAI, TR ZHANG, WU CHAO, XJ YE, PZ KOU, QR FAN, YH ZHANG, XC LIN, XF MENG, JF ZHO, JS WACHOLDER, S KNELLER, R BLOT, WJ TI COHORT STUDY AMONG WORKERS EXPOSED TO BENZENE IN CHINA .2. EXPOSURE ASSESSMENT SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE EXPOSURE ESTIMATES; BENZENE EXPOSURE; EXPOSURE ASSESSMENT METHOD; RECONSTRUCTION OF HISTORICAL EXPOSURE ID MORTALITY; RISK AB This report describes a retrospective exposure assessment method used in a follow-up mortality study of workers exposed to benzene. The approach quantified historical exposure to benzene in a multi-industry, multicenter cohort, involving 672 factories in 12 cities in China. Historical exposure data were collected to obtain exposure information related to 1,427 work units (departments) and 3,179 unique job titles from benzene-producing or -using factories in which written records and other data sources were evaluated. The basic unit for exposure assessment was a factory/work unit/job title combination which was considered separately during each of seven calendar-year time periods between 1949 and 1987 for a total of 18,435 exposure assignments. Historical information collected to estimate exposure included benzene monitoring data; lists of raw materials and factory products, and the percentage of benzene in each; the total amount and dates of use of benzene or benzene-containing materials; use of engineering controls and personal protective equipment; and other available exposure information. Overall, 38% (ranging from 3% for the earliest periods to 67% for the last period) of the estimates were based primarily on benzene monitoring data. In the absence of job-specific benzene monitoring data for a given calendar period, measurement results or exposure estimates for similar jobs and/or other calendar periods were used in conjunction with other exposure information to derive estimates. Estimated exposure levels are presented by industries and occupations. The highest average exposures during 1949-1987 were observed for the rubber and plastic industry (30.7 ppm), and for rubber glue applicators (52.6 ppm). (C) 1994 Wiley-Liss, Inc. C1 CHINESE ACAD PREVENT MED, INST OCCUPAT MED, BEIJING, PEOPLES R CHINA. STN PUBL HLTH & PREVENT INFECT, SHANGHAI, PEOPLES R CHINA. STN PUBL HLTH & PREVENT INFECT, CHENGDU, PEOPLES R CHINA. STN PUBL HLTH & PREVENT INFECT, CHUNQING, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, TIANJIN, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, HEILONGJIANG, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, HENAN, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, SHENYANG, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, SICHUAN, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, JIANGXI, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, NANCHANG, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, CANTON, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, JINZHOU, PEOPLES R CHINA. RP DOSEMECI, M (reprint author), NCI, EPIDEMIOL & BIOSTAT PROGRAM, OCCUPAT STUDIES SECT, 6130 EXECUT BLVD, ROOM 418, BETHESDA, MD 20892 USA. NR 15 TC 51 Z9 53 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0271-3586 EI 1097-0274 J9 AM J IND MED JI Am. J. Ind. Med. PD SEP PY 1994 VL 26 IS 3 BP 401 EP 411 DI 10.1002/ajim.4700260313 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PD297 UT WOS:A1994PD29700012 PM 7977413 ER PT J AU CHARLES, MA PETTITT, DJ MCCANCE, DR HANSON, RL BENNETT, PH KNOWLER, WC AF CHARLES, MA PETTITT, DJ MCCANCE, DR HANSON, RL BENNETT, PH KNOWLER, WC TI GRAVIDITY, OBESITY, AND NON-INSULIN-DEPENDENT DIABETES AMONG PIMA INDIAN WOMEN SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID POLYCYSTIC OVARY SYNDROME; HORMONE-BINDING GLOBULIN; GLUCOSE-TOLERANCE; PLASMA-INSULIN; RISK-FACTORS; POPULATION; MELLITUS; PARITY; NIDDM; HYPERINSULINEMIA AB PURPOSE: To evaluate the relationships among gravidity, obesity, and non-insulin-dependent diabetes mellitus in Pima Indian women. SUBJECTS AND METHODS: Pima Indian women (n = 2,779) participating in a longitudinal epidemiologic study of diabetes were evaluated in both cross-sectional and longitudinal analyses. RESULTS: The prevalence of non-insulin-dependent diabetes was higher among women who had never been pregnant than among those who had been pregnant (age- and obesity-adjusted odds ratio = 2.0; 95% confidence interval = 1.5 to 2.7). Controlled for age and obesity, nondiabetic women who had never been pregnant had significantly higher fasting plasma glucose concentrations by 2% (P = 0.004), higher fasting serum insulin concentrations by 8% (P = 0.09), and higher 2-hour serum insulin concentrations by 10% (P = 0.07) than nondiabetic women who had been pregnant. Among 1,025 women observed for an average of 8 years, those who had not been pregnant by the baseline examination were at significantly higher risk for developing non-insulin-dependent diabetes before the age of 40 years (incidence rate ratio = 1.5; 95% confidence interval = 1.2 to 2.1), but that difference could be accounted for by a higher degree of obesity. CONCLUSIONS: We hypothesize that Pima Indian women who have a high risk for non-insulin-dependent diabetes develop obesity and hyperinsulinemia at an early age, and that may be responsible for decreased fertility because of associated changes in sex hormones. C1 NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,DEPT DIABET,PHOENIX,AZ 85014. NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,ARTHRITIS EPIDEMIOL SECT,PHOENIX,AZ 85014. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 29 TC 22 Z9 22 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP PY 1994 VL 97 IS 3 BP 250 EP 255 DI 10.1016/0002-9343(94)90008-6 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA PG635 UT WOS:A1994PG63500010 PM 8092174 ER PT J AU SHERER, DM GLANTZ, JC METLAY, LA SINKIN, RA AF SHERER, DM GLANTZ, JC METLAY, LA SINKIN, RA TI MARKED TWIN-TWIN TRANSFUSION IN THE ABSENCE OF NONIMMUNE HYDROPS SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE TWIN-TWIN TRANSFUSION; PRENATAL ULTRASOUND AB The precise pathophysiology of development of nonimmune hydrops in either the recipient or donor twin associated with twin-twin transfusion syndrome is not entirely clear. At times the recipient twin may develop nonimmune hydrops, but at other times the donor twin, and infrequently both, may develop this ominous complication. We present an unusual case of this syndrome in which discordant twins, despite neonatal hematocrit levels of 86 and 21% were both nonhydropic and discuss the possible underlying pathophysiology of this occurrence. RP SHERER, DM (reprint author), GEORGETOWN UNIV,MED CTR,DEPT OBSTET & GYNECOL,NICHD,DIV INTRAMURAL,PERINATAL RES BRANCH,WASHINGTON,DC 20007, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0735-1631 J9 AM J PERINAT JI Am. J. Perinatol. PD SEP PY 1994 VL 11 IS 5 BP 317 EP 319 DI 10.1055/s-2007-994543 PG 3 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA PF977 UT WOS:A1994PF97700002 PM 7993507 ER PT J AU SHERER, DM SMITH, SA SANKO, SR AF SHERER, DM SMITH, SA SANKO, SR TI UTERINE SACCULATION SONOGRAPHICALLY MIMICKING AN ABDOMINAL PREGNANCY AT 20 WEEKS GESTATION SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE UTERINE SACCULATION; ABDOMINAL PREGNANCY; ULTRASOUND AB We present an unusual case in which sonographic findings consistent with abdominal pregnancy were associated with uterine sacculation, subsequently correctly diagnosed at laparotomy. RP SHERER, DM (reprint author), GEORGETOWN UNIV,MED CTR,DEPT OBSTET & GYNECOL,NICHD,DIV INTRAMURAL,PERINATAL RES BRANCH,WASHINGTON,DC 20007, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0735-1631 J9 AM J PERINAT JI Am. J. Perinatol. PD SEP PY 1994 VL 11 IS 5 BP 350 EP 352 DI 10.1055/s-2007-994552 PG 3 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA PF977 UT WOS:A1994PF97700011 PM 7993516 ER PT J AU SHERER, DM COOPER, EM SPOOR, C SERLETTI, BL WOODS, JR AF SHERER, DM COOPER, EM SPOOR, C SERLETTI, BL WOODS, JR TI RESOLUTION OF MARKED INTRAPARTUM FETAL TACHYCARDIA FOLLOWING INTRAVENOUS NALBUPHINE HYDROCHLORIDE SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE INTRAPARTUM FETAL HEART; TACHYCARDIA; FETAL BEHAVIOR; NALBUPHINE HYDROCHLORIDE AB We report a case of a patient who received nalbuphine during labor. The fetus was in an awake state, but when exposed to intravenous nalbuphine manifested quiet sleep. This suggests a physiological response and not a sign of fetal compromise. RP SHERER, DM (reprint author), GEORGETOWN UNIV,MED CTR,DEPT OBSTET & GYNECOL,NICHD,DIV INTRAMURAL,PERINATAL RES BRANCH,WASHINGTON,DC 20007, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0735-1631 J9 AM J PERINAT JI Am. J. Perinatol. PD SEP PY 1994 VL 11 IS 5 BP 367 EP 368 DI 10.1055/s-2007-994557 PG 2 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA PF977 UT WOS:A1994PF97700016 PM 7993521 ER PT J AU FUHRER, MJ AF FUHRER, MJ TI SUBJECTIVE WELL-BEING - IMPLICATIONS FOR MEDICAL REHABILITATION OUTCOMES AND MODELS OF DISABLEMENT SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE SUBJECTIVE WELL-BEING; PHYSICAL DISABILITIES; REHABILITATION OUTCOMES; LIFE SATISFACTION ID SPINAL-CORD INJURY; FUNCTIONAL ASSESSMENT SCALES; LONG-TERM ADJUSTMENT; LIFE SATISFACTION; PEOPLE ASSESS; QUALITY; HEALTH; DISABILITY; HANDICAP; LIVES AB Research regarding the subjective well-being (i.e., subjective quality of life as a whole) of persons with physical disabilities is considered from conceptual and methodologic perspectives. Relevant measurement scales, both single- and multiple-item, are reviewed, with special attention to measures-of-life satisfaction. Evidence about variables associated with subjective well-being is reviewed, based on studies of (1) people in general, (2) people with a variety of different disabling conditions and (3) persons with multiple sclerosis, stroke or spinal cord injury. Needed theoretic and empiric developments are discussed, including elaboration of the subjective aspects of impairments, disabilities and handicaps. RP FUHRER, MJ (reprint author), NICHHD,NCMRR,NIH BLDG 61E,ROOM 2A03,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 48 TC 100 Z9 102 U1 1 U2 7 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD SEP-OCT PY 1994 VL 73 IS 5 BP 358 EP 364 DI 10.1097/00002060-199409000-00010 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA PL292 UT WOS:A1994PL29200009 PM 7917167 ER PT J AU DIGIOVANNI, SR MADSEN, KM LUTHER, AD KNEPPER, MA AF DIGIOVANNI, SR MADSEN, KM LUTHER, AD KNEPPER, MA TI DISSOCIATION OF AMMONIAGENIC ENZYME ADAPTATION IN RAT S1 PROXIMAL TUBULES AND AMMONIUM EXCRETION RESPONSE SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE AMMONIAGENESIS; METABOLIC ACIDOSIS; ACID-BASE BALANCE; PHOSPHATE-DEPENDENT GLUTAMINASE ACTIVITY; GLUTAMATE DEHYDROGENASE ACTIVITY ID PHOSPHATE-DEPENDENT GLUTAMINASE; ACID-BASE-BALANCE; METABOLIC-ACIDOSIS; PHOSPHOENOLPYRUVATE CARBOXYKINASE; PERFUSED INVITRO; MESSENGER-RNA; NEPHRON; KIDNEY; INDUCTION; SEGMENTS AB We measured ammonium production rates, phosphate-dependent glutaminase (PDG) activity, and glutamate dehydrogenase (GDH) activity in microdissected S1 proximal tubules of rats to investigate the role of adaptations of PDG activity and GDH activity in response to a step increase in acid intake. In vivo ammonium excretion increased much more rapidly than did single-tubule ammonium production in vitro or ammoniagenic enzyme activities measured in microdissected tubules, manifesting an 85-fold increase in the first 24 h. In vitro ammonium production rates in microdissected tubules rose only twofold in the first 24 h, fourfold by day 2, and fivefold by day 4 of acid loading. The adaptation of PDG activity paralleled the increase in single-tubule ammoniagenic capacity measured in vitro. GDH activity, on the other hand, did not change significantly even after 4 days of acid loading. From these observations, we conclude that 1) the adaptation of in vitro ammoniagenic capacity in S1 proximal tubules is temporally associated with an adaptation in PDG activity and not GDH activity, and 2) a major portion of the increased ammonium excretion seen in the first 24 h is due to factors other than an adaptive increase in ammoniagenic enzyme activity. RP DIGIOVANNI, SR (reprint author), NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BLDG 10,ROOM 6N307,BETHESDA,MD 20892, USA. NR 30 TC 12 Z9 12 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD SEP PY 1994 VL 267 IS 3 BP F407 EP F414 PN 2 PG 8 WC Physiology SC Physiology GA PH383 UT WOS:A1994PH38300088 PM 8092254 ER PT J AU CASILLAS, CB TINNEY, JP KELLER, BB AF CASILLAS, CB TINNEY, JP KELLER, BB TI INFLUENCE OF ACUTE ALTERATIONS IN CYCLE LENGTH ON VENTRICULAR-FUNCTION IN CHICK-EMBRYOS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE CARDIOVASCULAR DEVELOPMENT; PRESSURE-VOLUME RELATIONS; BRADYCARDIA-TACHYCARDIA ID HEART-RATE PERTURBATION; DORSAL AORTIC FLOW; CARDIAC-OUTPUT; STROKE VOLUME; ENVIRONMENTAL HYPERTHERMIA; CARDIOVASCULAR FUNCTION; BLOOD-PRESSURE; RATE INCREASE; STAGE-24; HEMODYNAMICS AB Heart rate (HR), developed pressure, and stroke volume (SV) increase dramatically during cardiac morphogenesis. During acute changes in cycle length (CL), the chick embryo maintains cardiac output by a compensatory change in SV. We determined embryonic pressure-volume relations during alterations in CL in the stage 21 white Leghorn chick embryo to quantitate the relationship between CL and cardiac time intervals, ventricular preload, and ventricular function. CL was transiently altered to 73-191% of initial baseline CL with a l-mm randomly preheated or cooled metal probe applied to the sinus venosus. Isometric relaxation, diastolic filling, and systolic ejection times varied linearly with CL, whereas isometric contraction times were similar. SV varied linearly with CL, ejection time, and end-diastolic volume. In contrast to the mature heart, the relationship between SV and end-systolic pressure was inverse. Embryonic ventricular preload was influenced acutely by diastolic filling time, and cardiac output was optimized during changes in CL by ventricular-vascular interactions that matched SV inversely to HR. C1 UNIV ROCHESTER,SCH MED,DEPT PEDIAT,STRONG CHILDRENS RES CTR,NIH,ROCHESTER,NY 14642. FU NHLBI NIH HHS [HL-02498] NR 35 TC 16 Z9 16 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD SEP PY 1994 VL 267 IS 3 BP H905 EP H911 PN 2 PG 7 WC Physiology SC Physiology GA PH383 UT WOS:A1994PH38300006 PM 8092294 ER PT J AU MILLER, DS PRITCHARD, JB AF MILLER, DS PRITCHARD, JB TI NOCODAZOLE INHIBITION OF ORGANIC ANION SECRETION IN TELEOST RENAL PROXIMAL TUBULES SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE P-AMINOHIPPURATE; CONFOCAL MICROSCOPY; EPIFLUORESCENCE MICROSCOPY; EXCRETORY TRANSPORT; FLUORESCEIN; INTRACELLULAR COMPARTMENTATION; KILLIFISH; WINTER FLOUNDER ID TRANSPORT; HEPATOCYTES; MECHANISMS; CATIONS; CELLS AB The impact of the microtubule-disrupting drug nocodazole on renal tubular secretion of organic anions was examined in vitro using proximal tubular masses from teleost fish. Nocodazole reversibly inhibited 20-30% of the tubular accumulation of two model organic anions, p-aminohippurate and fluorescein (FL), by winter flounder tubular masses. However, the drug had no effect on the initial rate of organic anion uptake. Thus it did not reduce transport into the cells at the basolateral membrane, either directly by affecting basolateral organic anion transport proteins or indirectly by altering metabolism or ion gradients. Instead, epifluorescence video microscopy and digital image analysis of killifish tubules showed that nocodazole greatly reduced luminal accumulation of FL and had a smaller effect on cellular dye accumulation. Luminal FL accumulation returned to control levels when tubules were incubated in drug-free medium. Confocal fluorescence microscopy confirmed the marked reduction in luminal FL concentration and demonstrated that intracellular punctate FL accumulation was also markedly reduced. Finally, immunohistochemistry with an anti-tubulin antibody showed that the concentrations of nocodazole used in the above experiments reversibly disrupted microtubules within renal epithelial cells. These data indicate that a component of organic anion secretion in teleost proximal tubule is dependent on an intact microtubular network. C1 NIEHS,CELLULAR & MOLEC PHARMACOL LAB,COMPARAT MEMBRANE PHARMACOL SECT,RES TRIANGLE PK,NC 27709. MT DESERT ISL BIOL LAB,SALSBURY COVE,ME 04672. RP MILLER, DS (reprint author), NIEHS,CELLULAR & MOLEC PHARMACOL LAB,INTRACELLULAR REGULAT SECT,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 20 TC 35 Z9 35 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD SEP PY 1994 VL 267 IS 3 BP R695 EP R704 PN 2 PG 10 WC Physiology SC Physiology GA PH383 UT WOS:A1994PH38300058 PM 8092313 ER PT J AU REGIER, DA KAELBER, CT ROPER, MT RAE, DS SARTORIUS, N AF REGIER, DA KAELBER, CT ROPER, MT RAE, DS SARTORIUS, N TI THE ICD-10 CLINICAL FIELD TRIAL FOR MENTAL AND BEHAVIORAL-DISORDERS - RESULTS IN CANADA AND THE UNITED-STATES SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article AB Objective: To help evaluate the impact of proposed revisions to the chapter on mental and behavioral disorders for ICD-10, the World Health Organization (WHO) Division of Mental Health organized an international clinical field trial to evaluate draft clinical descriptions and diagnostic guidelines. The authors compare interrater diagnostic reliability results from this field trial for clinicians in Canada and the United States of America with those from all other clinicians worldwide, as well as with those from field trials conducted to evaluate drafts of DSM-III. Method: Two or more clinicians at each clinical center independently evaluated each patient, following a study protocol that allowed clinicians to list up to six diagnoses. In Canada and the United States, 96 clinicians completed 1,781 assessments among 491 patients, and elsewhere in the world 472 clinicians completed 7,495 assessments among 1,969 patients. Results: Summary kappa coefficients at two-, three-, and four-character ICD-IO code levels were 0.76, 0.65, and 0.52, respectively, for Canadian and U.S. clinicians and 0.83, 0.75, and 0.62 for clinicians elsewhere. The mean number of diagnoses per assessment for Canadian and U.S. clinicians was 2.1; for clinicians elsewhere it was 1.7. More multiple coding of diagnoses for substance use disorders, mood (affective) disorders, and personality disorders by Canadian and U.S. clinicians accounted for much of the difference in diagnostic coding and in interrater reliability between them and clinicians elsewhere. Conclusions: Interrater diagnostic reliability in Canada and the United States was similar to that of clinicians worldwide and also to results from the DSM-III field tests. Use of more multiple coding of selected disorders by Canadian and U.S. clinicians may reflect the influence of DSM-III and DSM-III-R, which encourage multiple diagnostic entries and the use of separate multiaxial coding for personality disorders, and may have reduced interrater concurrence for some categories. Further, collaborative development of ICD-10 with DSM-IV has aligned these two systems more closely. C1 WHO,DIV MENTAL HLTH,CH-1211 GENEVA,SWITZERLAND. RP REGIER, DA (reprint author), NIMH,DIV EPIDEMIOL & SERV RES,RM 10-105,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 14 TC 33 Z9 33 U1 2 U2 6 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 1994 VL 151 IS 9 BP 1340 EP 1350 PG 11 WC Psychiatry SC Psychiatry GA PE366 UT WOS:A1994PE36600017 PM 8067491 ER PT J AU DICKER, M LEIGHTON, EA AF DICKER, M LEIGHTON, EA TI TRENDS IN THE US PREVALENCE OF DRUG-USING PARTURIENT WOMEN AND DRUG-AFFECTED NEWBORNS, 1979 THROUGH 1990 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID PREGNANT-WOMEN; COCAINE USE; ABUSE; ALCOHOL; CARE AB Objectives. There has been a lack of reliable national data on the number of pregnant women using drugs and the number of newborns affected by such use. The major reasons for this lack have been inadequate sampling and data collection procedures and the lack of a risk assessment perspective in analysis. This paper corrects for these inadequacies. Methods. Data from 1979 through 1990 from the National Hospital Discharge Survey, an annual survey by the National Center for Health Statistics, were analyzed. Results. Between 1979 and 1990 there was a 576% increase in the rate of discharges of drug-using parturient women in the United States and a 456% increase in the rate of discharges of drug-affected newborns. After adjustment for underreporting, a ''best estimate'' of the number of discharges from 1988 through 1990 was about 88 000 per year for drug-using parturient women and about 48 000 per year for drug-affected newborns. Conclusions. Although the data support the occurrence of a national epidemic of drug use among pregnant women during the 1980s, the size and severity of this epidemic have been overstated. C1 WASHINGTON CONSULTING GRP,WASHINGTON,DC. NIDA,ROCKVILLE,MD. FU NIDA NIH HHS [NIDA 271-91-8324] NR 40 TC 21 Z9 21 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 1994 VL 84 IS 9 BP 1433 EP 1438 DI 10.2105/AJPH.84.9.1433 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PJ247 UT WOS:A1994PJ24700014 PM 8092367 ER PT J AU WILCOX, AJ SKJAERVEN, R IRGENS, LM AF WILCOX, AJ SKJAERVEN, R IRGENS, LM TI HARSH SOCIAL CONDITIONS AND PERINATAL SURVIVAL - AN AGE-PERIOD-COHORT ANALYSIS OF THE WORLD-WAR-II OCCUPATION OF NORWAY SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID WEIGHT; MORTALITY; HEIGHT; RATES AB Objectives. The hypothesis was tested that unfavorable social conditions are associated with poor perinatal natal survival through direct effects on pregnancy or, more indirectly, through effects on mothers born under such conditions. The occupation of Norway by Nazi Germany was used as a period of social hardship. Methods. Data from Norwegian vital statistics and the Medical Birth Registry were used to describe perinatal mortality during World War II and also a generation later, among babies born to mothers who had themselves been born during the war. Logistic regression was used to identify a possible cohort effect among mothers born in 1940 through 1944 compared With mothers born before or after that period. Results. Harsh conditions in Norway during the occupation increased childhood mortality. However, perinatal mortality declined during that period. Likewise, no adverse effect was seen on the survival of babies born to mothers who had themselves been born during the war (odds ratio = 1.00; 95% confidence interval = 0.96, 1.04). Conclusions. We find no evidence that wartime conditions in Norway impaired perinatal survival, either directly or through an effect on women born during the war. These data underscore how little is known about the ways that social conditions influence perinatal mortality. C1 UNIV BERGEN, MED INFORMAT & STAT SECT, BERGEN, NORWAY. UNIV BERGEN, MED BIRTH REGISTRY, BERGEN, NORWAY. UNIV BERGEN, DEPT PUBL HLTH & PRIMARY HLTH CARE, DIV PREVENT MED, BERGEN, NORWAY. RP WILCOX, AJ (reprint author), NIEHS, EPIDEMIOL BRANCH, RES TRIANGLE PK, NC 27709 USA. OI Wilcox, Allen/0000-0002-3376-1311 NR 22 TC 13 Z9 13 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 1994 VL 84 IS 9 BP 1463 EP 1467 DI 10.2105/AJPH.84.9.1463 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PJ247 UT WOS:A1994PJ24700019 PM 8092372 ER PT J AU POMMERENKE, FA MILLER, RW SRIVASTAVA, S ACKERMANN, SP AF POMMERENKE, FA MILLER, RW SRIVASTAVA, S ACKERMANN, SP TI TARGETING CANCER CONTROL - THE STATE CANCER CONTROL MAP AND DATA PROGRAM SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Note AB The State Cancer Control Map and Data Program (National Technical Information Service, Springfield, Va) allows state and county mortality maps and data tables to be tailored. according to the user's choice of cancer site, age, gender, race, county, and time period between 1953 and 1987. Counties and subpopulations within these maps and data tables that are identified as having exceptionally high rates of specific cancers can then be targeted for early detection or primary prevention. These maps and data tables provide a means for focusing state, local, and individual efforts to reduce cancer mortality in appropriate populations in areas with high mortality rates. C1 NCI,EARLY DETECT BRANCH,BETHESDA,MD 20892. NCI,EPIDEMIOL BRANCH,BETHESDA,MD 20892. CTR DIS CONTROL & PREVENT,DIV CANC PREVENT & CONTROL,ATLANTA,GA 30341. NR 15 TC 3 Z9 3 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 1994 VL 84 IS 9 BP 1479 EP 1482 DI 10.2105/AJPH.84.9.1479 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PJ247 UT WOS:A1994PJ24700022 PM 8092375 ER PT J AU ROMERO, R GOMEZ, R GALASSO, M MUNOZ, H ACOSTA, L YOON, BH SVINARICH, D COTON, DB AF ROMERO, R GOMEZ, R GALASSO, M MUNOZ, H ACOSTA, L YOON, BH SVINARICH, D COTON, DB TI MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA IN TERM AND PRETERM PARTURITION - EFFECT OF MICROBIAL INVASION OF THE AMNIOTIC CAVITY SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article DE CYTOKINES; INTRAUTERINE INFECTION; HUMAN PARTURITION ID BLOOD-CELL COUNT; CHEMOKINETIC PROPERTIES; CYTOKINE FAMILY; PROTEIN; LABOR; PROLIFERATION; INTERLEUKIN-6; EXPRESSION; ALPHA AB PROBLEM: This study was conducted to determine whether: (1) gestational age, parturition, and microbial invasion of the amniotic cavity (MIAC) are associated with changes in amniotic fluid concentrations of immunoreactive macrophage inflammatory protein-1 alpha; (2) amniotic fluid concentrations of macrophage inflammatory protein-1 alpha are correlated with the white blood cell count and the concentrations of interleukin-8 in amniotic fluid. METHOD: Amniotic fluid was retrieved by amniocentesis from 126 patients; 54 women with preterm labor and intact membranes (no MIAC-delivery at term, N = 21; no MIAC-preterm delivery, N = 16; MIAC-preterm delivery, N = 17); 62 patients at term (no labor, N = 19; labor-no MIAC, N = 20; labor-MIAC, N = 23); and 10 patients in the midtrimester of pregnancy. Amniotic fluid was cultured for aerobic, anaerobic and Mycoplasma species. Determinations of amniotic fluid macrophage inflammatory protein-1 alpha and interleukin-8 were performed with immunoassays validated for amniotic fluid (sensitivity: 14.2 pg/ml and 0.3 ng/ml, respectively). Kruskal-Wallis analysis of variance (ANOVA) for censored data, Mann-Whitney U test and Spearman's rank correlation were performed for analysis. RESULTS: 1) Amniotic fluid macrophage inflammatory protein-1 alpha was present in only 31.0% (9/29) of patients not in labor (midtrimester and term). 2) Patients with preterm labor and MIAC had higher amniotic fluid concentrations of macrophage inflammatory protein-1 alpha than those without MIAC (no MIAC-delivery at term: median 0.0 pg/ml, range 0.0-221.2; no MIAC-preterm delivery: median 37.4 pg/ml, range 0.0-494.6; MIAC-preterm delivery: median 7171.0 pg/ml, range 402.5-37994.0; P<0.00001). 3) Among patients at term, MIAC was associated with higher concentrations of amniotic fluid macrophage inflammatory protein-let than patients without MIAC (no labor: median 0.0 pg/ml, range 0.025.6; labor-no MIAC: median 16.7 pg/ml, range 0.0-161.6; labor-MIAC: median 103.8 pg/ml, range 0.0-4349.0, P<0.001). 4) Among patients in preterm labor, a strong correlation was found between amniotic fluid concentrations of macrophage inflammatory protein-1 alpha and interleukin-8 (r = 0.9, P<0.00001) and between amniotic fluid macrophage inflammatory protein-1 alpha concentrations and amniotic fluid white blood cell count (r = 0.6, P<0.0001). CONCLUSIONS: (1) Macrophage inflammatory protein-1 alpha is undetectable in most amniotic fluid samples from patients in the midtrimester of pregnancy and at term not in labor. (2) Microbial invasion of the amniotic cavity is associated with increased concentrations of immunoreactive amniotic fluid macrophage inflammatory protein-1 alpha in both term and preterm gestations. (3) Amniotic fluid macrophage inflammatory protein-1 alpha concentrations significantly correlate with interleukin-8 levels and white blood cell count in amniotic fluid. Our data strongly suggest a role for macrophage inflammatory protein-1 alpha in the mechanisms responsible for the recruitment of leukocytes into the amniotic cavity during the course of intrauterine infection. C1 NICHHD,PERINATOL RES BRANCH,BETHESDA,MD 20892. SEOUL NATL UNIV,SEOUL,SOUTH KOREA. RP ROMERO, R (reprint author), WAYNE STATE UNIV,HUTZEL HOSP,DEPT OBSTET & GYNECOL,4707 ST ANTOINE BLVD,DETROIT,MI 48201, USA. RI Yoon, Bo Hyun/H-6344-2011 NR 24 TC 79 Z9 81 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 8755-8920 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD SEP PY 1994 VL 32 IS 2 BP 108 EP 113 PG 6 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA PL846 UT WOS:A1994PL84600008 PM 7826499 ER PT J AU HURD, SS AF HURD, SS TI PULMONARY RESEARCH - LOOKING TO THE FUTURE SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material RP HURD, SS (reprint author), NHLBI,DIV LUNG DIS,BETHESDA,MD, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD SEP PY 1994 VL 150 IS 3 BP 610 EP 610 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA PH352 UT WOS:A1994PH35200002 PM 8087326 ER PT J AU HAN, SK BRODY, SL CRYSTAL, RG AF HAN, SK BRODY, SL CRYSTAL, RG TI SUPPRESSION OF IN-VIVO TUMORIGENICITY OF HUMAN LUNG-CANCER CELLS BY RETROVIRUS-MEDIATED TRANSFER OF THE HUMAN TUMOR-NECROSIS-FACTOR-ALPHA CDNA SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID GENE-TRANSFER; MURINE TUMOR; FACTOR TNF; GAMMA-INTERFERON; NUDE-MICE; INVIVO; INTERLEUKIN-2; EXPRESSION; LINES; PROLIFERATION AB The clinical use of tumor necrosis factor-alpha (TNF) is constrained by tumor cell resistance and systemic toxicity. Based on observations with murine tumors, we hypothesized that induction of local TNF production by the tumor may suppress growth of human cancer cells. To evaluate this, a human TNF cDNA was transferred to human lung cancer cell lines in vitro using a retrovirus vector to produce TNF cDNA-modified cell lines secreting TNF In vitro cell growth was similar for parental and modified cells. All cells were resistant to TNF The in vivo tumorigenicity of parental and modified cells was compared in nude mice. Animals injected subcutaneously with parental cells uniformly developed tumors. Tumor growth was markedly less for all modified cells, and this suppression of tumor development was reversed by anti-TNF antibody administration. Animals injected with a mixture of 50% modified and 50% parental cells or parental cell tumors injected with modified cells had decreased tumor growth, demonstrating that modified cells could suppress tumorigenicity. These data suggest that TNF can induce antitumor defenses to suppress in vivo human tumor cell growth and provide a rationale for transferring the human TNF cDNA directly to malignant cells for the therapy of human lung cancer. C1 NHLBI,PULM BRANCH,BETHESDA,MD 20892. NR 39 TC 29 Z9 29 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD SEP PY 1994 VL 11 IS 3 BP 270 EP 278 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA PH363 UT WOS:A1994PH36300004 PM 8086165 ER PT J AU PAPAC, DI HOYES, J TOMER, KB AF PAPAC, DI HOYES, J TOMER, KB TI DIRECT ANALYSIS OF AFFINITY-BOUND ANALYTES BY MALDI/TOF MS SO ANALYTICAL CHEMISTRY LA English DT Article ID IONIZATION MASS-SPECTROMETRY; CHROMATOGRAPHY; PROTEINS AB Identification of ligands separated with affinity chromatography has been facilitated by direct analysis of the bound ligand using matrix-assisted laser desorption time-of-flight mass spectrometry. Tbe mass spectral detection of analytes separated by immunoaffinity chromatography and immobilized metal ion affinity chromatography is shown. For example, cytochrome c is used as an affinity support to purify the anti-cytochrome c monoclonal antibody from ascites, and the mass spectrum of the anti-cytochrome c monoclonal antibody was obtained by direct analysis of an aliquot of the column bed. Direct analyses of metal binding proteins and phosphopeptides bound to immobilized metal ion affinity columns are also demonstrated. The method is characterized by minimal sample manipulation and high sensitivity with low picomoles and high femtomoles of analytes being readily observed. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. VG ANALYT,MANCHESTER M23 9LE,LANCS,ENGLAND. RI Tomer, Kenneth/E-8018-2013 NR 12 TC 74 Z9 74 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD SEP 1 PY 1994 VL 66 IS 17 BP 2609 EP 2613 DI 10.1021/ac00089a004 PG 5 WC Chemistry, Analytical SC Chemistry GA PD717 UT WOS:A1994PD71700006 ER PT J AU LINDEMAN, KS BAKER, SG HIRSHMAN, CA AF LINDEMAN, KS BAKER, SG HIRSHMAN, CA TI INTERACTION BETWEEN HALOTHANE AND THE NONADRENERGIC, NONCHOLINERGIC INHIBITORY SYSTEM IN PORCINE TRACHEALIS MUSCLE SO ANESTHESIOLOGY LA English DT Article DE ANESTHETICS, VOLATILE, HALOTHANE; LUNG(S), BRONCHODILATION; MUSCLE, SMOOTH, AIRWAY; NERVE(S), ELECTRICAL FIELD STIMULATION, NONADRENERGIC, NONCHOLINERGIC INHIBITORY SYSTEM; PHARMACOLOGY, NITRIC OXIDE ID VASOACTIVE-INTESTINAL-PEPTIDE; ENDOGENOUS NITRIC-OXIDE; SMOOTH-MUSCLE; HUMAN AIRWAYS; RESPONSES; RELAXATIONS; ATTENUATION; ISOFLURANE; MODULATION; ENFLURANE AB Background: Volatile anesthetics significantly affect cholinergic neural transmission in the airways and relax airway smooth muscle. Activation of the nonadrenergic, noncholinergic inhibitory neural pathway, which is thought to be mediated by nitric oxide, relaxes human and porcine airways. The purpose of the current study was to determine in the isolated porcine trachealis muscle whether relaxation of airway smooth muscle by halothane is mediated in part by activation of the nonadrenergic, noncholinergic inhibitory system. Methods: Isometric tension was measured in porcine trachealis muscle suspended in tissue baths in the presence of propranalol (10(-6) M). After stimulation of postsynaptic nicotinic cholinergic receptors with 1,1-dimethyl-4-phenyl-piper-azinium iodide (10(-4) M) to prevent contractile responses to subsequent electrical field stimulation, carbachol (3 x 10(-7) M) was added to increase tone. Nonadrenergic, noncholinergic relaxation responses to electrical field stimulation were then measured in the presence of inhibitors of nitric oxide synthase or L-arginine (the substrate for nitric oxide synthase), in the presence and absence halothane. Results: Electrical field stimulation produced frequency-dependent relaxations that were attenuated by inhibitors of nitric oxide synthase (NG-nitro-L-arginine methyl ester [L-NAME] or NG-monomethyl-L-arginine, 10(-4) M). Pretreatment with L-arginine (10(-4) M) prevented the effect of L-NAME. Halothane (0.5% or 1.0%) neither enhanced nor attenuated nonadrenergic, noncholinergic relaxations in the presence of L-NAME, D-NAME, L-arginine, or D-arginine. Conclusions: Halothane, at concentrations less than or equal to 1.0%, does not relax porcine airway smooth muscle in vitro by activating the nonadrenergic, noncholinergic inhibitory system. C1 JOHNS HOPKINS UNIV,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD. JOHNS HOPKINS UNIV,DEPT ENVIRONM HLTH SCI,BALTIMORE,MD. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD. FU NHLBI NIH HHS [HL02417] NR 24 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3 BP 641 EP 648 DI 10.1097/00000542-199409000-00018 PG 8 WC Anesthesiology SC Anesthesiology GA PG119 UT WOS:A1994PG11900016 PM 8092511 ER PT J AU LINDEMAN, KS BAKER, SG HIRSHMAN, CA AF LINDEMAN, KS BAKER, SG HIRSHMAN, CA TI INTERACTION BETWEEN HALOTHANE AND THE NONADRENERGIC, NONCHOLINERGIC INHIBITORY SYSTEM IN PORCINE TRACHEAL MUSCLE SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 JOHNS HOPKINS MED INST,BALTIMORE,MD 21287. NCI,BETHESDA,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3A SU S BP A1472 EP A1472 PG 1 WC Anesthesiology SC Anesthesiology GA PJ091 UT WOS:A1994PJ09101470 ER PT J AU MARTIN, JL DODGE, ML POHL, LR AF MARTIN, JL DODGE, ML POHL, LR TI IMMUNOCHEMICAL DETECTION OF COVALENTLY MODIFIED KIDNEY PROTEINS IN RATS TREATED WITH THE SEVOFLURANE DEGRADATION PRODUCT, COMPOUND-A (SEVO-OLEFIN) SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 JOHNS HOPKINS MED INST,DEPT ANESTHESIOL,BALTIMORE,MD 21287. NHLBI,CHEM PHARMACOL LAB,BETHESDA,MD 20892. NR 0 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3A SU S BP A436 EP A436 PG 1 WC Anesthesiology SC Anesthesiology GA PJ091 UT WOS:A1994PJ09100435 ER PT J AU MOODY, EJ HARRIS, BD WONG, G SKOLNICK, P AF MOODY, EJ HARRIS, BD WONG, G SKOLNICK, P TI EFFECTS OF SUBUNIT COMPOSITION ON ISOFLURANE ACTION AT CLONED GABA(A) RECEPTORS SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 NIH,NEUROSCI LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,DEPT ANESTHESIOL & CRIT MED,DIV CARDIAC ANESTHESIA,BALTIMORE,MD 21287. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3A SU S BP A470 EP A470 PG 1 WC Anesthesiology SC Anesthesiology GA PJ091 UT WOS:A1994PJ09100469 ER PT J AU SCHAFER, M IMAI, Y MOUSA, S ANTONIJEVIC, I UHL, GR STEIN, C AF SCHAFER, M IMAI, Y MOUSA, S ANTONIJEVIC, I UHL, GR STEIN, C TI PERIPHERAL OPIOID ANALGESIA IN INFLAMMATION - INCREASED SYNTHESIS AND ACCESSIBILITY OF OPIOID RECEPTORS ON SENSORY NERVES ARE CRITICAL FOR EFFICACY SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,DEPT ANESTHESIOL,BALTIMORE,MD 21224. NIDA,OFF DIRECTOR PRECLIN PHARMACOL,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3A SU S BP A919 EP A919 PG 1 WC Anesthesiology SC Anesthesiology GA PJ091 UT WOS:A1994PJ09100918 ER PT J AU TAKAHASHI, H KIRSCH, JR HASHIMOTO, K LONDON, ED KOEHLER, RC TRAYSTMAN, RJ AF TAKAHASHI, H KIRSCH, JR HASHIMOTO, K LONDON, ED KOEHLER, RC TRAYSTMAN, RJ TI PPBP[4-PHENYL-1(4-PHENYLBUTYL)PIPERIDINE], A POTENT SIGMA-RECEPTOR LIGAND, DECREASES BRAIN INJURY FOLLOWING TRANSIENT FOCAL ISCHEMIA IN CATS SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 JOHNS HOPKINS MED INST,DEPT ANESTHESIOL CCM,BALTIMORE,MD 21205. NIDA,BALTIMORE,MD. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3A SU S BP A848 EP A848 PG 1 WC Anesthesiology SC Anesthesiology GA PJ091 UT WOS:A1994PJ09100847 ER PT J AU KETTELHUT, BV METCALFE, DD AF KETTELHUT, BV METCALFE, DD TI PEDIATRIC MASTOCYTOSIS SO ANNALS OF ALLERGY LA English DT Review ID BULLOUS URTICARIA PIGMENTOSA; CUTANEOUS MASTOCYTOSIS; CHILDREN; SKIN AB Objective. The information presented will aid the practicing allergist in the recognition and management of pediatric-onset mastocytosis. Data Sources. Index Medicus from 1985 to present with keywords: mastocytosis; pediatrics; cutaneous. Limited to English language and to human disease. Study Selection. Information relative to mastocytosis in the pediatric age group to adulthood was reviewed. Results. Mastocytosis in children is an uncommon disease and is characterized by mast cell hyperplasia and release of mast cell mediators, particularly in the skin. It generally presents during the first 2 years of life. The most common manifestation is a solitary mastocytoma, with urticaria pigmentosa being the next most frequent manifestation. The most common initial presenting symptom of pediatric mastocytosis is pruritus. Complications of severe mastocytosis include formation of bullae and gastrointestinal bleeding attributed to high levels of circulating plasma histamine, which in turn stimulates gastric acid secretion. Conclusion. Treatment of pediatric mastocytosis is largely symptomatic. Prognosis seems to be somewhat related to the severity of the disease, with children with less extensive skin involvement tending to have the best chance to have resolution of the disease by adulthood. C1 NIAID,CLIN INVEST LAB,ALLERG DIS SECT,BETHESDA,MD 20892. RP KETTELHUT, BV (reprint author), CHILDRENS HOSP,MED CTR,DIV CLIN IMMUNOL & ALLERGY,ELLAND & BETHESDA AVE,CINCINNATI,OH 45229, USA. NR 35 TC 52 Z9 52 U1 0 U2 2 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 SN 0003-4738 J9 ANN ALLERGY JI Ann. Allergy PD SEP PY 1994 VL 73 IS 3 BP 197 EP 202 PG 6 WC Allergy SC Allergy GA PG917 UT WOS:A1994PG91700002 PM 8092552 ER PT J AU AVGERINOS, PC YANOVSKI, JA OLDFIELD, EH NIEMAN, LK CUTLER, GB AF AVGERINOS, PC YANOVSKI, JA OLDFIELD, EH NIEMAN, LK CUTLER, GB TI THE METYRAPONE AND DEXAMETHASONE SUPPRESSION TESTS FOR THE DIFFERENTIAL-DIAGNOSIS OF THE ADRENOCORTICOTROPIN-DEPENDENT CUSHING SYNDROME - A COMPARISON SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE METYRAPONE; DEXAMETHASONE; CUSHINGS SYNDROME; CORTICOTROPIN ID CORTICOTROPIN-RELEASING HORMONE; STIMULATION TEST; ACTH; CORTISOL AB Objective: To develop criteria for interpreting results of the metyrapone test for the differential diagnosis of the adrenocorticotropin (ACTH)-dependent Cushing syndrome and to compare its diagnostic accuracy with that of the high-dose dexamethasone suppression test. Design: Retrospective cohort study. Setting: Inpatient research ward. Patients: 186 patients believed to have the ACTH-dependent Cushing syndrome who had the metyrapone test, the dexamethasone test, and a surgical procedure to remove the source of excessive ACTH. Measurements: The sensitivity, specificity, and diagnostic accuracy were determined for the metyrapone test using urine excretion of hydroxysteroid and plasma levels of 11-deoxycortisol. For the dexamethasone suppression test, urine excretions of 17-hydroxysteroid (17-OHS) and free cortisol were used. Main Results: 156 patients had pituitary disease, 15 had ectopic ACTH secretion, and 15 had no diagnosis after pituitary surgery. Of those 15 patients, 14 were ultimately classified as having pituitary disease on the basis of follow-up, and 1 was found to have ACTH-independent Cushing syndrome. After administration of metyrapone, stimulation of 17-OHS excretion greater than 70% or of a plasma 11-deoxycortisol level greater than 400-fold did not result in the misclassification of any of the patients with surgically confirmed cases of ectopic ACTH secretion. When these criteria were combined, the percentage of correct predictions (122 of 186 [71%; 95% CI, 62% to 79%]) was higher than that for either steroid alone (116 of 186 [62%; CI, 52% to 71 %]) for excretion of 17-OHS and that for plasma 11-deoxycortisol (82 of 186 [44%; CI, 34% to 54%]). When the criteria for both the metyrapone test and the dexamethasone test were combined, the percentage of correct predictions (153 of 186 [82%; CI, 75% to 87%]) was higher than that obtained when the criteria for either test alone were used (P = 0.001). Similar results were found when the 15 patients with indeterminate surgery were assigned to the appropriate group on the basis of follow-up. When the criteria for both the metyrapone and dexamethasone tests were combined to identify patients with the pituitary Cushing syndrome, the sensitivity and diagnostic accuracy improved to 88% and 89%, respectively. Conclusions: The metyrapone test, which can be done in 48 hours, has a sensitivity and specificity for the diagnosis of the Cushing syndrome identical to that of the standard 6-day high-dose dexamethasone suppression test. Combining both tests results in greater accuracy than that obtained with either test alone. C1 NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. RP AVGERINOS, PC (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N262,BETHESDA,MD 20892, USA. NR 37 TC 40 Z9 40 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 1 PY 1994 VL 121 IS 5 BP 318 EP 327 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA PD701 UT WOS:A1994PD70100002 PM 8042820 ER PT J AU BOUMPAS, DT AF BOUMPAS, DT TI NIH STUDY OF RHEUMATOID-ARTHRITIS SO ANNALS OF INTERNAL MEDICINE LA English DT Letter RP BOUMPAS, DT (reprint author), NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 1 PY 1994 VL 121 IS 5 BP 389 EP 389 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PD701 UT WOS:A1994PD70100036 ER PT J AU HALTIA, M VIITANEN, M SULKAVA, R ALAHURULA, V POYHONEN, M GOLDFARB, L BROWN, P LEVY, E HOULDEN, H CROOK, R GOATE, A CLARK, R KORENBLAT, K PANDIT, S KELLER, HD LILIUS, L LIU, L AXELMAN, K FORSELL, L WINBLAD, B LANNFELT, L HARDY, J AF HALTIA, M VIITANEN, M SULKAVA, R ALAHURULA, V POYHONEN, M GOLDFARB, L BROWN, P LEVY, E HOULDEN, H CROOK, R GOATE, A CLARK, R KORENBLAT, K PANDIT, S KELLER, HD LILIUS, L LIU, L AXELMAN, K FORSELL, L WINBLAD, B LANNFELT, L HARDY, J TI CHROMOSOME 14-ENCODED ALZHEIMERS-DISEASE - GENETIC AND CLINICOPATHOLOGICAL DESCRIPTION SO ANNALS OF NEUROLOGY LA English DT Article ID PRECURSOR PROTEIN GENE; CREUTZFELDT-JAKOB DISEASE; CEREBRAL-HEMORRHAGE; MOLECULAR-CLONING; MUTATION; MYOCLONUS; LINKAGE; LOCUS; FAMILIES; CDNA AB A family of Finnish descent with very-early-onset Alzheimer's disease has been identified. Genetic analysis of this family eliminated the amyloid precursor protein gene as the pathogenic locus, but strongly implicated a locus on chromosome 14q23.4 between D14S52 and D14S55. The early age at onset of the disease (average, 36 years; range, 35-39 years), the rapid progression, and the early and prominent myoclonus, while they appear to be frequent findings in the chromosome 14-encoded form of Alzheimer's disease, raised the clinical suspicion of prion disease. However, sequencing the prion gene-coding region of 2 affected members of the pedigree failed to show any abnormality. Apart from the presence of modest cortical vacuolar change, the pathological features of our index patient appeared typical of Alzheimer's disease with abundant senile plaques immunoreactive with beta-amyloid, but not with prion protein antibodies. C1 UNIV S FLORIDA,DEPT PSYCHIAT,SUNCOAST ALZHEIMERS DIS LABS,TAMPA,FL 33613. UNIV HELSINKI,DEPT PATHOL,HELSINKI,FINLAND. KAROLINSKA INST,DEPT CLIN NEUROSCI,HUDDINGE,SWEDEN. UNIV KUOPIO,DEPT COMMUNITY HLTH & GEN PRACTICE,SF-70211 KUOPIO,FINLAND. KEMI CENT HOSP,DEPT NEUROL,KEMI,FINLAND. OULU UNIV HOSP,DEPT CLIN GENET,OULU,FINLAND. NIH,CENT NERVOUS SYST STUDIES LAB,BETHESDA,MD 20892. NYU,MED CTR,DEPT PATHOL,NEW YORK,NY 10016. NYU,MED CTR,DEPT PHARMACOL,NEW YORK,NY 10016. UNIV S FLORIDA,DEPT PHARMACOL,TAMPA,FL. UNIV S FLORIDA,DEPT NEUROL,TAMPA,FL 33620. WASHINGTON UNIV,SCH MED,DEPT PSYCHIAT,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT SURG,DIV HUMAN GENET,ST LOUIS,MO 63110. ST MARYS HOSP,SCH MED,DEPT BIOCHEM,PRION GRP,LONDON,ENGLAND. ST MARYS HOSP,SCH MED,DEPT BIOCHEM,DEMENTIA RES GRP,LONDON,ENGLAND. ST MARYS HOSP,SCH MED,DEPT NEUROL,LONDON,ENGLAND. RI Houlden, Henry/C-1532-2008; Hardy, John/C-2451-2009 OI Houlden, Henry/0000-0002-2866-7777; FU NHGRI NIH HHS [HG00469]; NIA NIH HHS [NIA-RO1 AG11871-01]; NINDS NIH HHS [NS30455] NR 36 TC 84 Z9 84 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD SEP PY 1994 VL 36 IS 3 BP 362 EP 367 DI 10.1002/ana.410360307 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA PF966 UT WOS:A1994PF96600006 PM 8080244 ER PT J AU HALLETT, M GLOCKER, FX DEUSCHL, G AF HALLETT, M GLOCKER, FX DEUSCHL, G TI MECHANISM OF ACTION OF BOTULINUM TOXIN SO ANNALS OF NEUROLOGY LA English DT Letter C1 UNIV FREIBURG,DEPT NEUROL,W-7800 FREIBURG,GERMANY. RP HALLETT, M (reprint author), NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BLDG 36,RM 4D04,BETHESDA,MD 20892, USA. RI Deuschl, Gunther/A-7986-2010 NR 4 TC 25 Z9 25 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD SEP PY 1994 VL 36 IS 3 BP 449 EP 450 DI 10.1002/ana.410360321 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA PF966 UT WOS:A1994PF96600020 PM 8080256 ER PT J AU FRAKER, DL NORTON, JA ALEXANDER, HR VENZON, DJ JENSEN, RT AF FRAKER, DL NORTON, JA ALEXANDER, HR VENZON, DJ JENSEN, RT TI SURGERY IN ZOLLINGER-ELLISON SYNDROME ALTERS THE NATURAL-HISTORY OF GASTRINOMA SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 114th Annual Scientific-Session of the American-Surgical-Association CY APR 07-09, 1994 CL SAN ANTONIO, TX SP AMER SURG ASSOC ID MULTIPLE ENDOCRINE NEOPLASIA; ISLET CELL TUMORS; DUODENAL GASTRINOMAS; SURGICAL-TREATMENT; MANAGEMENT; RESECTION AB Objective The authors assessed the impact of gastrinoma resection on the subsequent development of hepatic metastases in Zollinger-Ellison syndrome. Summary Background Data The symptoms of acid hypersecretion can be controlled medically in Zollinger-Ellison syndrome with high-dose pharmacologic therapy. The current role of surgery is curative excision of the gastrinoma. Because biochemical cure is obtained only in a portion of the patients and the neoplastic disease may be indolent in this syndrome, the ability of surgical resection of gastrinoma to alter or improve the subsequent development of hepatic metastases and mortality has not been defined. Methods One hundred twenty-four patients with the biochemical diagnosis of Zollinger-Ellison syndrome and no hepatic metastases on initial imaging studies were evaluated. Ninety-eight patients underwent surgical exploration for curative gastrinoma resections white 26 patients were managed medically. Long-term follow-up regarding development of hepatic metastases and survival were evaluated. Results Surgical exploration with gastrinoma excision resulted in a significantly decreased incidence of hepatic metastases 3% (3/98) compared with patients managed medically 23% (6/26) with comparable follow-up (p < 0.003). Two deaths due to metastatic gastrinoma occurred in the nonoperative group compared with no disease-specific deaths in the surgical group (p = 0.085). Conclusions For the patient with Zollinger-Ellison syndrome without metastatic disease, surgical exploration with attempted curative gastrinoma resection is recommended because it may alter the natural history of this syndrome. C1 NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. WASHINGTON UNIV,DEPT SURG,ST LOUIS,MO. NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892. RP FRAKER, DL (reprint author), NCI,SURG BRANCH,SURG METAB SECT,BLDG 10,ROOM 2B07,BETHESDA,MD 20892, USA. RI Venzon, David/B-3078-2008 NR 27 TC 125 Z9 126 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD SEP PY 1994 VL 220 IS 3 BP 320 EP 330 DI 10.1097/00000658-199409000-00008 PG 11 WC Surgery SC Surgery GA PH670 UT WOS:A1994PH67000008 PM 7916560 ER PT J AU WANG, Z BENCHEKROUN, MN SINHA, BK AF WANG, Z BENCHEKROUN, MN SINHA, BK TI POTENTIATION OF ANTITUMOR ACTIVITIES OF CARBOPLATIN AND CAMPTOTHECIN BY INTERLEUKIN-1-ALPHA AGAINST HUMAN OVARIAN-CARCINOMA IN-VIVO SO ANTICANCER RESEARCH LA English DT Article DE INTERLEUKIN-1; CARBOPLATIN; CAMPTOTHECIN; OVARIAN CARCINOMA; TUMOR XENOGRAFTS ID HUMAN-MELANOMA CELLS; NUDE-MICE; CANCER; CHEMOTHERAPY; COMBINATION; TUMORS AB Interleukin-1 alpha significantly potentiated the cytotoxicity Of carboplatin (8-fold) and camptothecin (4-fold) during simultaneous drug exposure in human ovarian NIH: OVCAR-3 cancer cells in vitro. Treatment of human ovarian tumor cells grown as xenografts in nude mice with IL-1 alpha followed by either carboplatin or CTP-11 at minimally toxic doses significantly (2-3-fold and 7-fold for carboplatin and CTP-II, respectively) enhanced antitumor activity of either agent alone, indicating that IL-1 alpha-drug combinations may be potentially move effective for the treatment of ovarian tumors, including those difficult to cure in the clinic. C1 NCI,CLIN PHARMACOL BRANCH,BIOCHEM & MOLEC PHARMACOL SECT,BETHESDA,MD 20892. NR 20 TC 7 Z9 7 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD SEP-OCT PY 1994 VL 14 IS 5A BP 1723 EP 1726 PG 4 WC Oncology SC Oncology GA QE791 UT WOS:A1994QE79100006 PM 7847805 ER PT J AU DEFILIPPI, R PRETE, SP GIULIANI, A SILVI, E YAMAUE, H NIERODA, CA GREINER, JW DEVECCHIS, L BONMASSAR, E AF DEFILIPPI, R PRETE, SP GIULIANI, A SILVI, E YAMAUE, H NIERODA, CA GREINER, JW DEVECCHIS, L BONMASSAR, E TI DIFFERENTIAL-EFFECTS OF RECOMBINANT INTERFERON-ALPHA AND 5-FLUOROURACIL AGAINST COLON-CANCER CELLS OR AGAINST PERIPHERAL-BLOOD MONONUCLEAR-CELLS SO ANTICANCER RESEARCH LA English DT Article DE IFN-ALPHA; 5-FU; COLON CANCER; LYMPHOCYTES ID CARCINOEMBRYONIC ANTIGEN EXPRESSION; MEDIATED CYTOTOXICITY; MONOCLONAL-ANTIBODIES; COLORECTAL-CARCINOMA; FLUOROURACIL; LINES; COMBINATION; GAMMA; NK AB Comparative studies on the suppressive effects of recombinant interferon-alpha (IFN-alpha), 5-fluorouracil (5-FU), or IFN-alpha + 5-FU have been performed in vitro on colon carcinoma cells (HT-29 cell line) and PHA-stimulated mononuclear cells (MNC) of peripheral blood obtained from healthy donors. IFN-alpha was used at 500 U/ml against HT-29 cells and at 1000 U/ml against MNC on day I of culture; 5-FU was used cat 250 mu M against HT-29 find at 1400 mu M against MNC on day 2 of culture. The results show that: (a) IFN-alpha inhibited MNC and HT-29 cells by 13.4% and 32.9%, respectively; (b) 5-FU inhibited MNC and HT-29 cells by 54.7% and 87.0%, respectively; (c) IFN-alpha + 5-FU resulted in. a stronger inhibition of HT-29 cells (i.e., 96.1%). In contrast, that combination was significantly less suppressive than 5-FU alone when MNC were used as targets (i.e., 35.9% inhibition). Natural cell-mediated cytotoxic activity relative to 10(6) MNC was not markedly altered by all agents alone or in combination Moreover, treatment with IFN-alpha, 5-FU or IFN-alpha + 5-FU resulted in a marked increase in the number of HT-29 cells positive for the CEA surface antigen. These data seem to provide further rational support of the clinical use of IFN-alpha + 5-FU in colorectal cancer, based on the differential toxicity of this drug combination on tumor versus normal immunocompetent cells. C1 UNIV ROMA TOR VERGATA,DEPT EXPTL MED & BIOCHEM SCI,CHAIR PHARMACOL,I-00173 ROME,ITALY. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. IST DERMOPAT IMMACOLATA,I-00167 ROME,ITALY. NR 28 TC 9 Z9 9 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD SEP-OCT PY 1994 VL 14 IS 5A BP 1767 EP 1773 PG 7 WC Oncology SC Oncology GA QE791 UT WOS:A1994QE79100012 PM 7847809 ER PT J AU SHAMON, LA CHEN, C MEHTA, RG STEELE, V MOON, RC PEZZUTO, JM AF SHAMON, LA CHEN, C MEHTA, RG STEELE, V MOON, RC PEZZUTO, JM TI A CORRELATIVE APPROACH FOR THE IDENTIFICATION OF ANTIMUTAGENS THAT DEMONSTRATE CHEMOPREVENTIVE ACTIVITY SO ANTICANCER RESEARCH LA English DT Article DE ANTIMUTATION; CHEMOPREVENTION; MAMMARY GLAND; ORGAN CULTURE; SALMONELLA TYPHIMURIUM ID PREVENTION; CANCER AB Seventy natural and synthetic compounds were tested for potential to inhibit mutation induced by 7,12-dimethylbenz(a)anthracene (DMBA) in Salmonella typhimurium strain TM677. Results were compared with their ability to inhibit DMBA-induced preneoplastic lesions in a mouse mammary gland organ culture system. The response mediated by fifty-five of the test compounds was either positive or negative in both test systems, indicating that the combined use of these assays should aid in the discovery of antimutagenic agents that have cancer chemopreventive potential. C1 UNIV ILLINOIS, COLL PHARM, DEPT MED CHEM & PHARMACOGNOSY, CHICAGO, IL 60612 USA. UNIV ILLINOIS, COLL MED, CTR SPECIALIZED CANC, CHICAGO, IL 60612 USA. UNIV ILLINOIS, COLL PHARM, PROGRAM COLLABORAT RES PHARMACEUT SCI, CHICAGO, IL 60612 USA. NCI, CHEMOPREVENT BRANCH, BETHESDA, MD 20852 USA. FU NCI NIH HHS [N01-CN95173, P01 CA48112] NR 20 TC 14 Z9 14 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD SEP-OCT PY 1994 VL 14 IS 5A BP 1775 EP 1778 PG 4 WC Oncology SC Oncology GA QE791 UT WOS:A1994QE79100013 PM 7847810 ER PT J AU BOYER, PL DING, JP ARNOLD, E HUGHES, SH AF BOYER, PL DING, JP ARNOLD, E HUGHES, SH TI SUBUNIT SPECIFICITY OF MUTATIONS THAT CONFER RESISTANCE TO NONNUCLEOSIDE INHIBITORS IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REVERSE-TRANSCRIPTASE SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID AMINO-ACID SUBSTITUTIONS; ESCHERICHIA-COLI; HIV-1-SPECIFIC INHIBITORS; INSERTION MUTAGENESIS; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; DRUG; EXPRESSION; ANALOGS; IDENTIFICATION AB We constructed plasmid vectors that simultaneously express both the p66 and p51. subunits of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) in Escherichia coli. These vectors allow us to generate HIV-1 RT heterodimers in which either the p66 or the p51 subunit has the wild-type sequence and the other subunit has a specific amino acid substitution. We used these vectors to express HIV-1 RT heterodimers containing several different amino acid substitutions reported to confer resistance to nonnucleoside inhibitors. Most of the amino acid substitutions conferred resistance to nonnucleoside inhibitors R86183 (TIBO) and TSAO-m(3)T only when present in the p66 subunit of the p66-p51 heterodimer; heterodimers that contained a wild-type p66 subunit and a mutant p51 subunit remained sensitive to the inhibitors. However, there was one mutation, E138K, that conferred drug resistance when the mutation was present in the p51 subunit. The corresponding heterodimer with the E138K mutation in the p66 subunit and a wild-type p51 subunit remained sensitive to the inhibitors. Analysis of the three-dimensional structure of HIV-1 RT indicated that residue 138 of the p51 subunit is in the nonnucleoside inhibitor-binding pocket while residue 138 of the p66 subunit is not. The mutagenesis results, combined with structural data, support the idea that the nonnucleoside inhibitors exert their effects by binding to a hydrophobic pocket in the RT heterodimer and that mutations which give rise to drug resistance directly interfere with the interactions between the nonnucleoside inhibitors and HIV-1 RT. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RUTGERS STATE UNIV,CTR ADV BIOTECHNOL & MED,PISCATAWAY,NJ 08854. FU NCI NIH HHS [N01-CO-74101] NR 46 TC 77 Z9 77 U1 0 U2 0 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 SEP PY 1994 VL 38 IS 9 BP 1909 EP 1914 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA PF108 UT WOS:A1994PF10800007 PM 7529011 ER PT J AU PENDLAND, SL PISCITELLI, SC SCHRECKENBERGER, PC DANZIGER, LH AF PENDLAND, SL PISCITELLI, SC SCHRECKENBERGER, PC DANZIGER, LH TI IN-VITRO ACTIVITIES OF METRONIDAZOLE AND ITS HYDROXY METABOLITE AGAINST BACTEROIDES SPP SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID FRAGILIS GROUP; UNITED-STATES; SUSCEPTIBILITY; DESACETYLCEFOTAXIME; CLARITHROMYCIN; CEFOTAXIME; INVITRO; SYNERGY AB Metronidazole is metabolized to two major oxidative products: an acid metabolite and a hydroxy metabolite. While the activity of the acid metabolite is negligible, the activity of the hydroxy metabolite is approximately 65% of the activity of the parent drug. Pharmacokinetic studies of metronidazole and its hydroxy metabolite have shown that the MICs of both compounds remain above the MICs for most anaerobic organisms over an 8-h dosing interval. By a checkerboard assay, the combined activities of metronidazole and the hydroxy metabolite were examined against 4 quality control strains of Bacteroides species. Macrobroth tube dilutions were set up with Wilkins-Chalgren broth. Serial twofold dilutions of each agent were performed to achieve final concentrations ranging from 0.06 to;4.0 mu g/ml. The MICs for Bacteroides fragilis and B. distasonis were 1.0 mu g/ml for both parent drug and metabolite. For B. thetaiotaomicron and B. ovatus, the MICs of metronidazole and the hydroxy metabolite were 1.0 and 2.0 mu g/ml, respectively. Synergy was determined by calculating the fractional inhibitory concentration (FIC) index. The interpretative criteria for the FIC index were as follows: synergy, FIC less than or equal to 0.5; partial synergy, 0.51 to 0.75; indifference, FIC 0.76 to 4.0; and antagonism, FIC >4.0. Partial synergy was observed for the four anaerobes tested, with FIC indices ranging from 0.63 to 0.75. On the basis of this data, in vitro susceptibilities to agents such as metronidazole may ultimately require reevaluation to account for active metabolites. C1 UNIV ILLINOIS,COLL PHARM,DEPT PHARM PRACTICE M-C 886,CHICAGO,IL 60612. UNIV ILLINOIS,DEPT PATHOL,CHICAGO,IL. NIH,WARREN G MAGNUSON CLIN CTR,DEPT PHARM,BETHESDA,MD. NR 32 TC 22 Z9 22 U1 0 U2 0 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 SEP PY 1994 VL 38 IS 9 BP 2106 EP 2110 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA PF108 UT WOS:A1994PF10800038 PM 7811027 ER PT J AU DROPULIC, B JEANG, KT AF DROPULIC, B JEANG, KT TI INTRACELLULAR SUSCEPTIBILITY TO RIBOZYMES IN A TETHERED SUBSTRATE-RIBOZYME PROVIRUS MODEL IS NOT PREDICTED BY SECONDARY STRUCTURES OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 RNAS IN-VITRO SO ANTISENSE RESEARCH AND DEVELOPMENT LA English DT Note ID ANTISENSE RNA; THERAPEUTIC AGENTS; HAIRPIN RIBOZYME; EXPRESSION; DNA; INFECTIVITY; PARAMETERS; INHIBITION AB We have assessed the sensitivity of different sites in HIV-I genomic RNA to ribozymes. Ribozymes targeted to sequences in U5, Pol, Env, RRE, or R were positioned into nef of an infectious HIV-1 provirus. When these proviral DNAs were introduced into HeLa CD4(+) cells, recombinant viruses that contain ribozymes tethered to genomic RNA or viral mRNAs were produced. The growth kinetics of ribozyme-containing viruses in CD4(+) lymphocytes (MT4 cells) were distinctly delayed when compared to control viruses. On the basis of the ability of a particular ribozyme to inhibit virus replication, we inferred intracellular ribozyme-sensitive sites. We found that although ribozyme sensitivity in vitro could be correlated with predicted secondary structures of target RNAs, such in vivo correlations could not be made when using the HIV provirus model. We conclude that both Zuker algorithm computer modeling of substrate RNA secondary structures and in vitro cleavage efficiencies cannot be reliably used to determine HIV-1 ribozyme sensitive sites in vivo. C1 NIAID,MOLEC MICROBIOL LAB,MOLEC VIROL SECT,BETHESDA,MD 20892. RI Jeang, Kuan-Teh/A-2424-2008 NR 27 TC 18 Z9 18 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1050-5261 J9 ANTISENSE RES DEV JI Antisense Res. Dev. PD FAL PY 1994 VL 4 IS 3 BP 217 EP 221 PG 5 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA PL225 UT WOS:A1994PL22500010 PM 7849493 ER PT J AU BUCKHEIT, RW FLIAKASBOLTZ, V DECKER, WD ROBERSON, JL PYLE, CA WHITE, EL BOWDEN, BJ MCMAHON, JB BOYD, MR BADER, JP NICKELL, DG BARTH, H ANTONUCCI, TK AF BUCKHEIT, RW FLIAKASBOLTZ, V DECKER, WD ROBERSON, JL PYLE, CA WHITE, EL BOWDEN, BJ MCMAHON, JB BOYD, MR BADER, JP NICKELL, DG BARTH, H ANTONUCCI, TK TI BIOLOGICAL AND BIOCHEMICAL ANTI-HIV ACTIVITY OF THE BENZOTHIADIAZINE CLASS OF NONNUCLEOSIDE REVERSE-TRANSCRIPTASE INHIBITORS SO ANTIVIRAL RESEARCH LA English DT Article DE BENZOTHIADIAZINE; NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR; MECHANISM OF ACTION; COMBINATION THERAPY; STRUCTURE-ACTIVITY RELATIONSHIP ID IMMUNODEFICIENCY-VIRUS TYPE-1; TIBO DERIVATIVES; ANTIVIRAL ACTIVITY; POTENT INHIBITOR; NATURAL-PRODUCTS; VIRAL RESISTANCE; REPLICATION; DRUG; 3'-AZIDO-3'-DEOXYTHYMIDINE; THERAPY AB A series of benzothiadiazine derivatives were screened against the human immunodeficiency virus (HIV) and certain structure-activity relationships were defined for anti-HIV activity in this chemical class. The selected representative NSC 287474 was a highly potent inhibitor of HIV-induced cell killing and HIV replication in a variety of human cell lines, as well as in fresh human peripheral blood lymphocytes and macrophages. The compound was active against a panel of biologically diverse laboratory and clinical strains of HIV-1, including the AZT-resistant strain G910-6. However, the agent was inactive against HIV-2, and also against both nevirapine- and pyridinone-resistant strains (N119 and A17) of HIV-1, which are cross-resistant to several structurally diverse nonnucleoside reverse transcriptase inhibitors. The compound selectively inhibited HIV-1 reverse transcriptase, but not HIV-2 reverse transcriptase. Combination of NSC 287474 with AZT synergistically inhibited HIV-1-induced cell killing in vitro. The compound did not inhibit the replication of the Rauscher murine leukemia retrovirus or the simian immunodeficiency virus. The benzothiadiazine class of compounds represents a new active anti-HIV-1 chemotype within the diverse group of nonnucleoside reverse transcriptase inhibitors. C1 SO RES INST,MICROBIOL RES DEPT,BIRMINGHAM,AL 35255. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DRUG DISCOVERY RES & DEV,FREDERICK,MD 21702. NCI,DIV CANC TREATMENT,ANTIVIRAL EVALUAT BRANCH,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. WARNER LAMBERT PARKE DAVIS,PARKE DAVIS PHARMACEUT RES DIV,ANN ARBOR,MI 48105. RP BUCKHEIT, RW (reprint author), FREDERICK CANC RES & DEV CTR,SO RES INST,DIV VIRUS RES,431 AVIAT WAY,FREDERICK,MD 21701, USA. FU NCI NIH HHS [N01-CM-37818]; NIAID NIH HHS [P30 AI27767] NR 46 TC 64 Z9 65 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD SEP PY 1994 VL 25 IS 1 BP 43 EP 56 DI 10.1016/0166-3542(94)90092-2 PG 14 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA PE234 UT WOS:A1994PE23400004 PM 7529014 ER PT J AU LIU, KJ JIANG, JJ SWARTZ, HM SHI, XG AF LIU, KJ JIANG, JJ SWARTZ, HM SHI, XG TI LOW-FREQUENCY EPR DETECTION OF CHROMIUM(V) FORMATION BY CHROMIUM(VI) REDUCTION IN WHOLE LIVE MICE SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID HAMSTER V-79 CELLS; RED-BLOOD-CELLS; SINGLE-STRAND BREAKS; ALKALI-LABILE SITES; CHICK-EMBRYO LIVER; CARCINOGEN CHROMATE; FREE-RADICALS; DNA LESIONS; GLUTATHIONE-REDUCTASE; SODIUM CHROMATE(VI) AB Measurements by direct low frequency EPR spectroscopy provide the first evidence that Cr(V) is generated in one-electron. reduction of Cr(VI) in live mice. The Cr(V) yield reached a maximum about 10 min following Cr(VI) intravenous injection and then decayed slowly with a life time of approximately 37 min. The time for the Cr(V) EPR signal to reach maximum intensity increased with the dose of Cr(VI). A discernible EPR signal was still observable at a dose as low as 0.1 mmol/kg. The Cr(V) was found predominantly in the liver, with a small amount in the blood. No Cr(V) signal was detectable in heart, spleen, kidney, and lung. Pretreatment of the animals with metal ion chelators, ethylenediaminetetraacetic acid, diethylenetriaminepentaacetic acid, and 1,10-phenanthroline significantly reduced the intensity of the Cr(V) signal that was observed. (C) 1994 Academic Press,Inc. C1 DARTMOUTH COLL, SCH MED, DEPT RADIOL, HANOVER, NH 03755 USA. NCI, EXPTL PATHOL LAB, BETHESDA, MD 20892 USA. RI Shi, Xianglin/B-8588-2012 FU NCRR NIH HHS [RR-01811]; NIGMS NIH HHS [GM 34250] NR 46 TC 53 Z9 53 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 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD SEP PY 1994 VL 313 IS 2 BP 248 EP 252 DI 10.1006/abbi.1994.1384 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PE541 UT WOS:A1994PE54100008 PM 8080269 ER PT J AU BATHON, JM HWANG, JJ SHIN, LH PRECHT, PA TOWNS, MC HORTON, WE AF BATHON, JM HWANG, JJ SHIN, LH PRECHT, PA TOWNS, MC HORTON, WE TI TYPE-VI COLLAGEN-SPECIFIC MESSENGER-RNA IS EXPRESSED CONSTITUTIVELY BY CULTURED HUMAN SYNOVIAL FIBROBLASTS AND IS SUPPRESSED BY INTERLEUKIN-1 SO ARTHRITIS AND RHEUMATISM LA English DT Article ID RHEUMATOID-ARTHRITIS; EXTRACELLULAR-MATRIX; III COLLAGENS; CELLS; TISSUE; LOCALIZATION; FIBRONECTIN; PROTEIN; CHAINS; PROSTAGLANDIN-E2 AB Objective. Type VI collagen is a prominent constituent of the synovial extracellular matrix. The cellular source of this matrix protein and the identity of local factors in synovium that may regulate its expression have not been delineated, however. We examined the capacity of human fibroblast-like synovial cells to synthesize type VI collagen as well as the effect of interleukin-1 (IL-1) on this expression. Methods. RNA was extracted from cultured human synovial cells derived from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Northern blots were analyzed using sequence-specific probes, and steady-state messenger RNA (mRNA) levels of the 3 alpha(VI) procollagen chains were measured. The effect of IL-1 treatment on these levels was determined. Results. Abundant expression of 3 characteristic mRNA transcripts, corresponding to the ol (4.2-kb), alpha 2 (3.5-kb), and alpha 3 (8.5-kb) chains of type VI procollagen, was observed in untreated cells derived from RA and OA patients. IL-1 treatment consistently suppressed steady-state mRNA levels for all 3 alpha(VI) procollagen chains in a time- and dose-dependent manner. Tumor necrosis factor cu induced a response similar to that of IL-1, while IL-2 was ineffective in this regard. Indomethacin partially restored alpha(VI) mRNA expression in IL-1-treated cells. Conclusion. These studies provide novel data demonstrating abundant steady-state levels of mRNA transcripts coding for all 3 type VI procollagen polypeptides in human synovial fibroblast-like cells, as well as coordinated down-regulation of these transcripts by IL-1. Local production of IL-1 may thus constitute an important means in vivo of regulating the production of type VI collagen. C1 JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NIA,BALTIMORE,MD 21224. RP BATHON, JM (reprint author), JOHNS HOPKINS ASTHMA & ALLERGY CTR,ROOM 5A24,5501 HOPKINS BAYVIEW CIRCLE,BALTIMORE,MD 21224, USA. NR 40 TC 25 Z9 26 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1994 VL 37 IS 9 BP 1350 EP 1356 DI 10.1002/art.1780370913 PG 7 WC Rheumatology SC Rheumatology GA PJ938 UT WOS:A1994PJ93800012 PM 7945500 ER PT J AU MILLER, EK AF MILLER, EK TI NEOCORTICAL MEMORY TRACES SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Discussion ID INFERIOR TEMPORAL CORTEX RP MILLER, EK (reprint author), NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892, USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD SEP PY 1994 VL 17 IS 3 BP 488 EP 489 PG 2 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA PH245 UT WOS:A1994PH24500055 ER PT J AU MURRAY, EA AF MURRAY, EA TI RELATIONAL BUT NOT SPATIAL MEMORY - THE TASK AT HAND SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Discussion ID FORNIX TRANSECTION; RHESUS-MONKEYS; ASSOCIATION RP MURRAY, EA (reprint author), NIMH,NEUROPSYCHOL LAB,BLDG 49,ROOM 1B80,BETHESDA,MD 20892, USA. NR 9 TC 0 Z9 0 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD SEP PY 1994 VL 17 IS 3 BP 489 EP 490 PG 2 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA PH245 UT WOS:A1994PH24500056 ER PT J AU SUZUKI, WA AF SUZUKI, WA TI WHAT CAN NEUROANATOMY TELL US ABOUT THE FUNCTIONAL COMPONENTS OF THE HIPPOCAMPAL MEMORY SYSTEM SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Discussion ID IMPAIRMENT; LESIONS; CORTEX; MONKEY RP SUZUKI, WA (reprint author), NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892, USA. NR 8 TC 4 Z9 4 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD SEP PY 1994 VL 17 IS 3 BP 496 EP 498 PG 3 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA PH245 UT WOS:A1994PH24500063 ER PT J AU BOINSKI, S AF BOINSKI, S TI AFFILIATION PATTERNS AMONG MALE COSTA-RICAN SQUIRREL-MONKEYS SO BEHAVIOUR LA English DT Article ID SAIMIRI-OERSTEDI; SOCIAL-ORGANIZATION; SEXUAL SEGREGATION; BEHAVIOR; SCIUREUS; FIELD; EVOLUTION; DOMINANCE; ONTOGENY; PRIMATES AB Remarkably close male bonding exists among Costa Rican squirrel monkeys, Saimiri oerstedi. In this population males were philopatric, exhibited no male-male within-troop aggression, and only very slight evidence for a dominance hierarchy. Juvenile, young and full adult males were spatially clumped in same-age male cohorts. A less intense, secondary association was also shown between the young and full adult male cohorts. These associations were most dense over a spatial scale of 5 m or less, but can also be detected in a 5-10 m distance from a focal male. Males also cooperated in 1) sexual investigation of females during the mating season, 2) aggressive interactions with males of neighboring troops, and 3) valiant defense of infants and subadults from potential predators. In contrast, the spatial association among adult females never exceeded random expectations and only a transitory period of cooperation was observed among mothers during the birth season. Furthermore, there was little evidence of bonds between the sexes. Seasonal variation in affiliation patterns was best explained by fluctuations in food availability and, secondarily, reproductive activity. These results are surprising both from the perspective of the general pattern of male affiliation among primates and the often marked aggression and dominance relationships among males documented in captive and wild populations of South American squirrel monkeys. The ultimate explanation is suggested to be the disparate distribution of fruit resources exploited by South and Central American squirrel monkeys, mediated by effects on female affiliation and dispersal patterns. C1 UNIV FLORIDA,DIV COMPARAT MED,GAINESVILLE,FL 32611. NIH,CTR ANIM,COMPARAT ETHOL LAB,POOLESVILLE,MD 20837. RP BOINSKI, S (reprint author), UNIV FLORIDA,DEPT ANTHROPOL,1350 TURLINGTON,GAINESVILLE,FL 32611, USA. NR 59 TC 29 Z9 30 U1 2 U2 13 PU E J BRILL PI LEIDEN PA PO BOX 9000, 2300 PA LEIDEN, NETHERLANDS SN 0005-7959 J9 BEHAVIOUR JI Behaviour PD SEP PY 1994 VL 130 BP 191 EP 209 DI 10.1163/156853994X00523 PN 3-4 PG 19 WC Behavioral Sciences; Zoology SC Behavioral Sciences; Zoology GA PZ206 UT WOS:A1994PZ20600004 ER PT J AU WHALLEY, T SOKOLOFF, A AF WHALLEY, T SOKOLOFF, A TI THE N-ETHYLMALEIMIDE-SENSITIVE PROTEIN THIOL-GROUPS NECESSARY FOR SEA-URCHIN EGG CORTICAL-GRANULE EXOCYTOSIS ARE HIGHLY EXPOSED TO THE MEDIUM AND ARE REQUIRED FOR TRIGGERING BY CA2+ SO BIOCHEMICAL JOURNAL LA English DT Article ID SEA-URCHIN EGGS; VESICULAR TRANSPORT; VESICLE EXOCYTOSIS; CALCIUM SENSITIVITY; PLASMA-MEMBRANE; FUSION PROTEIN; RELEASE; CELLS; INHIBITION; DISCHARGE AB It is known that sea-urchin egg cortical-granule exocytosis is inhibited by agents such as N-ethylmaleimide (NEM) which modify thiol groups. The fusion-related proteins modified by these agents have yet to be identified, nor is there information regarding the topography of these thiol groups. Furthermore, the step in cortical-granule exocytosis at which these thiol groups participate is unknown. In this study we have investigated the topological properties of, and the temporal requirement for the function of, the fusion-related thiol groups by treating the isolated exocytotic apparatus with high-molecular-mass dextrans and BSA carrying thiol-reactive 3-(2-pyridyldithio)propionate groups. The dextran derivatives inhibited exocytosis. The BSA derivative was much less inhibitory. Inhibition was reversed by treatment with dithiothreitol. When NEM was added to the dextran-derivative-treated exocytotic apparatus, treatment with dithiothreitol completely reversed inhibition, indicating that the dextran derivatives inhibit by reacting at the NEM-sensitive sites. A pulse of Ca2+ applied in the presence of inhibitors did not trigger any fusion following the removal of the inhibitor by dithiothreitol. These data show that the thiol groups, the modification of which by NEM inhibits exocytosis, are exposed to the medium in terms of their accessibility to macromolecules. They also show that the fusion-related thiol groups are required during the Ca2+-dependent stage of exocytosis. RP WHALLEY, T (reprint author), NICHHD,THEORET & PHYS BIOL LAB,BLDG 10,RM 10D09,BETHESDA,MD 20892, USA. OI Whalley, Tim/0000-0003-3362-0006 NR 48 TC 13 Z9 13 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 SEP 1 PY 1994 VL 302 BP 391 EP 396 PN 2 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PF657 UT WOS:A1994PF65700012 PM 7522436 ER PT J AU WONG, P BORST, DE FARBER, D DANCIGER, JS TENNISWOOD, M CHADER, GJ VANVEEN, T AF WONG, P BORST, DE FARBER, D DANCIGER, JS TENNISWOOD, M CHADER, GJ VANVEEN, T TI INCREASED TRPM-2/CLUSTERIN MESSENGER-RNA LEVELS DURING THE TIME OF RETINAL DEGENERATION IN MOUSE MODELS OF RETINITIS-PIGMENTOSA SO BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE LA English DT Article DE RETINAL DEGENERATION; TRPM-2; CLUSTERIN; APOPTOSIS; RETINITIS PIGMENTOSA ID PROGRAMMED CELL-DEATH; BETA-SUBUNIT; RD MOUSE; CGMP-PHOSPHODIESTERASE; GENE-EXPRESSION; MESSENGER-RNA; DEVELOPMENTAL EXPRESSION; CLUSTERIN GENE; MUTANT MICE; PROTEIN AB Retinitis pigmentosa (RP) is a genetically and clinically heterogeneous group of human disorders that is characterized by diminished retinal function, visual cell loss, and blindness. Elevated levels of TRPM-2/clusterin mRNA, a marker for the apoptotic process, have been reported in retinas from patients with advanced stage RP. In the present study we examine TRPM-2/clusterin expression in two genetically distinct mouse models of RP, the rd (retinal degeneration) and rds (retinal degeneration slow) mice. We establish that in advanced postretinal degenerative stages of the rd mutant the retinal TRPM-2/clusterin mRNA levels are highly elevated, as is seen in the case of human RP. Examination of TRPM-2/clusterin mRNA levels in retina and whole eyes from the rd mouse and morphologically normal controls during the period of retinal degeneration (postnatal days 8-21) in the rd phenotype shows that TRPM-2/clusterin mRNA levels are elevated in the rd animal, and this increase begins just after postnatal day 10 and remains high for the remainder of the time course examined. Northern analysis of rds retina and whole eyes shows a delayed increase in TRPM-2/clusterin mRNA levels relative to the rrl profile, coinciding with the known period of rds retinal degeneration (postnatal day 14 to 1 year). In each case, the onset of increased TRPM-2/clusterin mRNA levels coincides with the time of photoreceptor cell death. C1 UNIV CALIF LOS ANGELES, SCH MED, JULES STEIN EYE INST, LOS ANGELES, CA 90024 USA. W ALTON JONES CELL SCI CTR, LAKE PLACID, NY 12946 USA. GOTHENBURG UNIV, DEPT ZOOL, S-40031 GOTHENBURG, SWEDEN. RP WONG, P (reprint author), NEI, RETINAL CELL & MOLEC BIOL LAB, BETHESDA, MD 20892 USA. FU NEI NIH HHS [EYO8285] NR 45 TC 29 Z9 29 U1 0 U2 1 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0829-8211 J9 BIOCHEM CELL BIOL JI Biochem. Cell Biol. PD SEP-OCT PY 1994 VL 72 IS 9-10 BP 439 EP 446 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QN213 UT WOS:A1994QN21300011 PM 7605616 ER PT J AU BAKER, SG AF BAKER, SG TI REGRESSION-ANALYSIS OF GROUPED SURVIVAL-DATA WITH INCOMPLETE COVARIATES - NONIGNORABLE MISSING-DATA AND CENSORING MECHANISMS SO BIOMETRICS LA English DT Note DE CATEGORICAL DATA; COMPOSITE LINEAR MODEL; MISSING DATA; PARTIALLY OBSERVED COVARIATES; SURVIVAL ANALYSIS AB Previous methods for the analysis of survival data with incomplete covariates have assumed that the missing-data and censoring mechanisms are ignorable. We relax both assumptions for the analysis of grouped survival data. RP BAKER, SG (reprint author), NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,EPN 344,6130 EXECUT BLVD,MSC 7354,BETHESDA,MD 20892, USA. NR 13 TC 12 Z9 12 U1 1 U2 1 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 1994 VL 50 IS 3 BP 821 EP 826 DI 10.2307/2532794 PG 6 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA PL748 UT WOS:A1994PL74800020 PM 7981401 ER PT J AU XIE, TD MARSZALEK, P CHEN, YD TSONG, TY AF XIE, TD MARSZALEK, P CHEN, YD TSONG, TY TI RECOGNITION AND PROCESSING OF RANDOMLY FLUCTUATING ELECTRIC SIGNALS BY NA,K-ATPASE SO BIOPHYSICAL JOURNAL LA English DT Article ID FREE-ENERGY TRANSDUCTION; MEMBRANE-PROTEINS; FIELD; ACTIVATION; OSCILLATIONS; TRANSPORT; NOISE; (NA,K)-ATPASE; FREQUENCY; DYNAMICS AB Previous work has shown that Na,K-ATPase of human erythrocytes can extract free energy from sinusoidal electric fields to pump cations up their respective concentration gradients. Because regularly oscillating waveform is not a featu re of the transmembrane electric potential of cells, questions have been raised whether these observed effects are biologically relevant. Here we show that a random-telegraph fluctuating electric field (RTF) consisting of alternating square electric pulses with random lifetimes can also stimulate the Rb+-pumping mode of the Na,K-ATPase. The net RTF-stimulated, ouabain-sensitive Rb+ pumping was monitored with Rb-86(+). The tracer-measured, Rb+ influx exhibited frequency and amplitude dependencies that peaked at the mean frequency of 1.0 kHz and amplitude of 20 V/cm. At 4 degrees C, the maximal pumping activity under these optimal conditions was 28 Rb+/RBC-hr, which is approximately 50% higher than that obtained with the sinusoidal electric field. These findings indicate that Na,K-ATPase can recognize an electric signal, either regularly oscillatory or randomly fluctuating, for energy coupling, with high fidelity. The use of RTF for activation also allowed a quantitative theoretical analysis of kinetics of a membrane transport model of any complexity according to the theory of electroconformational coupling (ECC) by the diagram methods. A four-state ECC model was shown to produce the amplitude and the frequency windows of the Rb+-pumping if the free energy of interaction of the transporter with the membrane potential was to include a nonlinear quadratic term. Kinetic constants for the ECC model have been derived. These results indicate that the ECC is a plausible mechanism for the recognition and processing of electric signals by proteins of the cell membrane. C1 HONG KONG UNIV SCI & TECHNOL,DEPT BIOCHEM,KOWLOON,HONG KONG. UNIV MINNESOTA,DEPT BIOCHEM,ST PAUL,MN 55108. NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. NR 38 TC 68 Z9 68 U1 1 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 1994 VL 67 IS 3 BP 1247 EP 1251 PG 5 WC Biophysics SC Biophysics GA PE377 UT WOS:A1994PE37700036 PM 7811939 ER PT J AU NICHOLS, RC RABEN, N AF NICHOLS, RC RABEN, N TI HINTS FOR DIRECT SEQUENCING OF PCR-GENERATED SINGLE-STRANDED-DNA SO BIOTECHNIQUES LA English DT Note ID POLYMERASE CHAIN-REACTION; RNA C1 NIAMS,CTR CLIN,BETHESDA,MD. NR 6 TC 11 Z9 11 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD SEP PY 1994 VL 17 IS 3 BP 412 EP 414 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PF201 UT WOS:A1994PF20100002 PM 7818886 ER PT J AU SLIGHTOM, JL BOCK, JH SIEMIENIAK, DR HURST, GD BEATTIE, KL AF SLIGHTOM, JL BOCK, JH SIEMIENIAK, DR HURST, GD BEATTIE, KL TI NUCLEOTIDE SEQUENCING DOUBLE-STRANDED PLASMIDS WITH PRIMERS SELECTED FROM A NONAMER LIBRARY SO BIOTECHNIQUES LA English DT Article ID DNA; STRATEGY; HYBRIDIZATION; HEXAMERS; WALKING AB Nonamer primers, selected from a nonamer library, were tested by sequencing two plasmid subclones containing known insert sequences. These sequences were scanned (nonamer-mapped) against the 2391-member nonamer library to identify all members that share a 100% match at only one site. A total of 59 nonamers were tested using a slightly modified T7 polymerase sequencing procedure for double-stranded DNA. The success rate for nonamer primed reactions was about 60%, and single-stranded coverage was obtained for approximately 90% of each plasmid insert The results presented demonstrate that a nonamer library, with as few as 2391 members, can greatly aid the completion of many sequencing projects by reducing the number of required custom primers. With the development of a technique for the rapid identification of all useful library primers for a particular sequencing project, one could envision a high-throughput shotgun-type sequencing procedure that would not require large numbers of subclones. C1 UNIV MICHIGAN,NIH,ANN ARBOR,MI. GENOSYS BIOTECHNOL,THE WOODLANDS,TX. HOUSTON ADV RES CTR,THE WOODLANDS,TX 77381. RP SLIGHTOM, JL (reprint author), KALAMAZOO COLL,MOLEC BIOL UNIT 7242267510,KALAMAZOO,MI 49007, USA. NR 21 TC 6 Z9 6 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD SEP PY 1994 VL 17 IS 3 BP 536 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PF201 UT WOS:A1994PF20100027 PM 7818908 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 A REVISED EUROPEAN-AMERICAN CLASSIFICATION OF LYMPHOID NEOPLASMS - A PROPOSAL FROM THE INTERNATIONAL LYMPHOMA STUDY-GROUP SO BLOOD LA English DT Review ID LARGE-CELL LYMPHOMA; REED-STERNBERG CELLS; NON-HODGKINS-LYMPHOMA; ACUTE LYMPHOBLASTIC-LEUKEMIA; EPSTEIN-BARR-VIRUS; CHRONIC LYMPHOCYTIC-LEUKEMIA; POLYMERASE CHAIN-REACTION; RECEPTOR GENE REARRANGEMENTS; LARGE GRANULAR LYMPHOCYTES; T(14-18) CHROMOSOMAL TRANSLOCATION C1 NCI, DEPT PATHOL, BETHESDA, MD 20892 USA. FREE UNIV BERLIN, KLINIKUM BENJAMIN FRANKLIN, DEPT PATHOL, W-1000 BERLIN, GERMANY. UNIV TEXAS, HLTH SCI CTR, DEPT PATHOL, SAN ANTONIO, TX 78284 USA. QUEEN ELIZABETH HOSP, DEPT PATHOL, HONG KONG, HONG KONG. STANFORD UNIV, SCH MED, DEPT PATHOL, STANFORD, CA 94305 USA. UNIV TOULOUSE 3, FAC MED PURPAN, DEPT PATHOL, F-31062 TOULOUSE, FRANCE. UNIV LOUVAIN, DEPT PATHOL, LOUVAIN, BELGIUM. UNIV ARIZONA, SCH MED, DEPT PATHOL, TUCSON, AZ USA. UCL, SCH MED, DEPT PATHOL, LONDON W1N 8AA, ENGLAND. CORNELL UNIV, MED CTR, NEW YORK HOSP, DEPT PATHOL, NEW YORK, NY 10021 USA. UNIV WURZBURG, DEPT PATHOL, W-8700 WURZBURG, GERMANY. UNIV BOLOGNA, DEPT PATHOL, BOLOGNA, ITALY. HOSP VIRGEN SALUD, DEPT PATHOL, TOLEDO, SPAIN. UNIV COPENHAGEN, DEPT PATHOL, HERLEV, DENMARK. UNIV OXFORD, JOHN RADCLIFFE HOSP, DEPT CELLULAR SCI, OXFORD OX3 9DU, ENGLAND. UNIV PERUGIA, INST HEMATOL, I-06100 PERUGIA, ITALY. RP HARRIS, NL (reprint author), HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT PATHOL, WARREN 2, BOSTON, MA 02114 USA. OI Piris, Miguel A/0000-0001-5839-3634 NR 296 TC 5064 Z9 5214 U1 14 U2 91 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 SEP 1 PY 1994 VL 84 IS 5 BP 1361 EP 1392 PG 32 WC Hematology SC Hematology GA PE387 UT WOS:A1994PE38700002 PM 8068936 ER PT J AU BODINE, DM SEIDEL, NE GALE, MS NIENHUIS, AW ORLIC, D AF BODINE, DM SEIDEL, NE GALE, MS NIENHUIS, AW ORLIC, D TI EFFICIENT RETROVIRUS TRANSDUCTION OF MOUSE PLURIPOTENT HEMATOPOIETIC STEM-CELLS MOBILIZED INTO THE PERIPHERAL-BLOOD BY TREATMENT WITH GRANULOCYTE-COLONY-STIMULATING FACTOR AND STEM-CELL FACTOR SO BLOOD LA English DT Article ID MEDIATED GENE-TRANSFER; BONE-MARROW CELLS; PROGENITOR CELLS; IN-VIVO; AUTOLOGOUS TRANSPLANTATION; ADENOSINE-DEAMINASE; MICE; RECONSTITUTION; CSF; CIRCULATION C1 ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38105 USA. RP BODINE, DM (reprint author), NIH, NATL CTR HUMAN GENOME RES,GENE TRANSFER LAB, HEMATOPOIESIS SECT,BLDG 49, ROOM 3A14, BETHESDA, MD 20892 USA. NR 38 TC 108 Z9 115 U1 0 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 SEP 1 PY 1994 VL 84 IS 5 BP 1482 EP 1491 PG 10 WC Hematology SC Hematology GA PE387 UT WOS:A1994PE38700016 PM 7520774 ER PT J AU GOODMAN, S XIAO, X DONAHUE, RE MOULTON, A MILLER, J WALSH, C YOUNG, NS SAMULSKI, RJ NIENHUIS, AW AF GOODMAN, S XIAO, X DONAHUE, RE MOULTON, A MILLER, J WALSH, C YOUNG, NS SAMULSKI, RJ NIENHUIS, AW TI RECOMBINANT ADENOASSOCIATED VIRUS-MEDIATED GENE-TRANSFER INTO HEMATOPOIETIC PROGENITOR CELLS SO BLOOD LA English DT Article ID HUMAN GAMMA-GLOBIN; BONE-MARROW CELLS; STEM-CELLS; ADENOASSOCIATED VIRUS; RETROVIRAL VECTORS; EXPRESSION; INTEGRATION; MICE; TRANSDUCTION; INFECTION C1 NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. UNIV PITTSBURGH,DEPT BIOL,PITTSBURGH,PA. FU NHLBI NIH HHS [HL 48347-03] NR 41 TC 142 Z9 144 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 1994 VL 84 IS 5 BP 1492 EP 1500 PG 9 WC Hematology SC Hematology GA PE387 UT WOS:A1994PE38700017 PM 8068942 ER PT J AU GJERSET, GF PIKE, MC MOSLEY, JW HASSETT, J FLETCHER, MA DONEGAN, E PARKER, JW COUNTS, RB ZHOU, Y KASPER, CK OPERSKALSKI, EA BUCKLEY, J GAIENNIE, J HARRIS, M LEE, H NOWICKI, MJ SUCCAR, M KLEINMAN, SH DIETRICH, SL LUSHER, JM SCHIFF, ER LIAN, ECY ALEDORT, LM HILGARTNER, MW STEVENS, CD TAYLOR, PE KOERPER, MA BUSCH, MP LEWIS, BH GJERSET, GF HOLLINGSWORTH, CG NEMO, GJ HOAK, J ALTER, HJ DALESSIO, DJ GRADY, GF HOLLAND, PV ROSE, NR SEEFF, LB WITTES, J AF GJERSET, GF PIKE, MC MOSLEY, JW HASSETT, J FLETCHER, MA DONEGAN, E PARKER, JW COUNTS, RB ZHOU, Y KASPER, CK OPERSKALSKI, EA BUCKLEY, J GAIENNIE, J HARRIS, M LEE, H NOWICKI, MJ SUCCAR, M KLEINMAN, SH DIETRICH, SL LUSHER, JM SCHIFF, ER LIAN, ECY ALEDORT, LM HILGARTNER, MW STEVENS, CD TAYLOR, PE KOERPER, MA BUSCH, MP LEWIS, BH GJERSET, GF HOLLINGSWORTH, CG NEMO, GJ HOAK, J ALTER, HJ DALESSIO, DJ GRADY, GF HOLLAND, PV ROSE, NR SEEFF, LB WITTES, J TI EFFECT OF LOW-PURITY AND INTERMEDIATE-PURITY CLOTTING FASTER THERAPY ON PROGRESSION OF HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION IN CONGENITAL CLOTTING DISORDERS SO BLOOD LA English DT Article ID FACTOR-VIII CONCENTRATE; SERIAL CD4 COUNTS; HEMOPHILIC PATIENTS; CLASSIC HEMOPHILIA; IMMUNE-SYSTEM; HIV; TRANSFUSION; INHIBITION; AIDS C1 UNIV SO CALIF,SCH MED,LOS ANGELES,CA 90032. PUGET SOUND BLOOD CTR,SEATTLE,WA 98104. MT SINAI MED CTR,NEW YORK,NY 10029. UNIV MIAMI,MIAMI,FL 33152. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. HUNTINGTON MEM HEMOPHILIA CTR,LOS ANGELES,CA. WAYNE STATE UNIV,DETROIT,MI 48202. GREATER NEW YORK BLOOD PROGRAM,NEW YORK,NY. CORNELL UNIV,MED CTR,ITHACA,NY 14853. IRWIN MEM BLOOD BANK,SAN FRANCISCO,CA. ALTA BATES COMMUNITY HOSP,SAN FRANCISCO,CA. NHLBI,SEATTLE,WA. FU NHLBI NIH HHS [N01-HB-4-7003, N01-HB-9-7074, N01-HB-4-7002] NR 27 TC 20 Z9 20 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 1994 VL 84 IS 5 BP 1666 EP 1671 PG 6 WC Hematology SC Hematology GA PE387 UT WOS:A1994PE38700039 PM 7915149 ER PT J AU SHU, XO JIN, F LINET, MS ZHENG, W CLEMENS, J MILLS, J GAO, YT AF SHU, XO JIN, F LINET, MS ZHENG, W CLEMENS, J MILLS, J GAO, YT TI DIAGNOSTIC-X-RAY AND ULTRASOUND EXPOSURE AND RISK OF CHILDHOOD-CANCER SO BRITISH JOURNAL OF CANCER LA English DT Article ID NON-HODGKINS-LYMPHOMA; WEST CUMBRIA; BOMB SURVIVORS; CHILDREN BORN; LEUKEMIA; RADIATION; SEASCALE; PREGNANCY; MORTALITY; INVITRO AB In a population-based case-control study of 642 childhood cancer cases and the same number of matched controls in Shanghai, China, we evaluated the relationship between diagnostic X-ray (preconception, pre- and post-natal) and antenatal ultrasound exposure and the subsequent risk of developing three major types of childhood cancer (acute leukaemia, lymphoma and brain tumours) and all childhood neoplasms combined. Consistent with previous studies, prenatal X-ray exposure was found to be associated with an 80% increased risk of childhood cancers, although the estimation was based on 4% and 2% exposed cases and controls and was only marginally statistically significant (P = 0.08). Post-natal X-ray exposure was also linked with a small elevation in the risk of all cancers and the major categories of malignancies in children. Little evidence, however, was found to relate parental preconception X-ray exposure with the subsequent cancer risk in offspring, regardless of the exposure window and the anatomical site of X-ray exposures. This study adds further to the growing literature indicating that antenatal ultrasound exposure is probably not associated with an increased risk of childhood cancer. C1 SHANGHAI CANC INST,DEPT EPIDEMIOL,SHANGHAI,PEOPLES R CHINA. NICHHD,EPIDEMIOL BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. UNIV MINNESOTA,DIV EPIDEMIOL,MINNEAPOLIS,MN 55455. RP SHU, XO (reprint author), UNIV MINNESOTA,DIV PEDIAT EPIDEMIOL CLIN RES,BOX 422 UMHC,MINNEAPOLIS,MN 55455, USA. NR 35 TC 89 Z9 92 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD SEP PY 1994 VL 70 IS 3 BP 531 EP 536 DI 10.1038/bjc.1994.340 PG 6 WC Oncology SC Oncology GA PD313 UT WOS:A1994PD31300028 PM 8080742 ER PT J AU PURCELL, H AF PURCELL, H TI EMOTIONAL ECLIPSE OF THE HEART SO BRITISH JOURNAL OF CLINICAL PRACTICE LA English DT Editorial Material ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY DISEASE; BLOOD-PRESSURE; STRESS; CIVILIANS; ONSET; WAR C1 NIH,CARDIOL BRANCH,BETHESDA,MD 20892. RP PURCELL, H (reprint author), ROYAL BROMPTON HOSP,DEPT CARDIOL,LONDON SW3 6LY,ENGLAND. NR 34 TC 0 Z9 0 U1 0 U2 0 PU MEDICOM INTERNATIONAL PI KINGSTON-UPON-THAMES PA QUADRANT, 118 LONDON RD, KINGSTON-UPON-THAMES, ENGLAND KT2 6QJ SN 0007-0947 J9 BRIT J CLIN PRACT JI Br. J. Clin. Pract. PD SEP-OCT PY 1994 VL 48 IS 5 BP 228 EP 229 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA PF829 UT WOS:A1994PF82900002 PM 7917812 ER PT J AU FIBACH, E SCHECHTER, AN NOGUCHI, CT RODGERS, GP AF FIBACH, E SCHECHTER, AN NOGUCHI, CT RODGERS, GP TI REDUCING ERYTHROPOIETIN IN CULTURES OF HUMAN ERYTHROID PRECURSORS ELEVATES THE PROPORTION OF FETAL HEMOGLOBIN SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE HEMATOPOIESIS; PROLIFERATION; DIFFERENTIATION; RBC; HEMOGLOBINOPATHIES ID SICKLE-CELL-ANEMIA; GAMMA-GLOBIN SYNTHESIS; HEMOGLOBIN-SYNTHESIS; LIQUID CULTURE; BETA-THALASSEMIA; HYDROXYUREA; PROGENITORS; DISEASE; STIMULATION; MATURATION AB In order to clarify the mechanism of the effect of erythropoietin (Epo) on the fetal haemoglobin (HbF) phenotype of peripheral erythrocytes, we studied the dose-response effect of Epo on HbF production by erythroid precursors derived from the peripheral blood of normal adult individuals and grown in a two-phase liquid culture system. The proportion of HbF out of the total haemoglobin (Hb) content (%HbF) was dependent on the duration of exposure to Epo; on day 6 it comprised up to 15%, but dropped to < 2% on day 14. Both cell yield and cellular Hi,content were markedly increased by high (1 U/ml) Epo, compared to normal physiological (20-50 mU/ml) levels, but neither the initial nor final %HbF were dependent on the increased Epo dose. However, when cells grown with high Epo were transferred on day 7 to low Epo, their progeny contained by day 14 a higher %HbF as compared to cells that were continuously exposed to high Epo. This was accompanied by acceleration and synchronization of their maturation process, as evidenced by their morphology, density and size, and restriction on cell multiplication, as indicated by the lower cell yield. These results are consistent with the following model. As early erythroid precursors, with relatively high HbF, mature under steady-state levels of Epo, HbA production predominates and HbF is diluted. However, when such precursors are switched from high to low levels of Epo they undergo a synchronized, accelerated maturation which shortens the period of HbA production, leading to a decreased Hb content and a relatively high proportion of HbF. This mechanism may contribute to the elevated HbF observed following Epo administration (due to short half-life of Epo in vivo). and might also explain the HbF-augmenting effect of Epo administered together with hydroxyurea observed in patients with sickle cell anaemia. C1 NIDDK,BIOL CHEM LAB,BETHESDA,MD. RP FIBACH, E (reprint author), HADASSAH UNIV HOSP,DEPT HAEMATOL,POB 12000,IL-91120 JERUSALEM,ISRAEL. NR 43 TC 17 Z9 17 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD SEP PY 1994 VL 88 IS 1 BP 39 EP 45 DI 10.1111/j.1365-2141.1994.tb04974.x PG 7 WC Hematology SC Hematology GA PF569 UT WOS:A1994PF56900006 PM 7528530 ER PT J AU ABASSI, ZA GOLOMB, E AGBARIA, R ROLLER, PP TATE, J KEISER, HR AF ABASSI, ZA GOLOMB, E AGBARIA, R ROLLER, PP TATE, J KEISER, HR TI HYDROLYSIS OF IODINE-LABELED URODILATIN AND ANP BY RECOMBINANT NEUTRAL ENDOPEPTIDASE EC.3.4.24.11 SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE ATRIAL NATRIURETIC PEPTIDE; URODILATIN; NEUTRAL ENDOPEPTIDASE; HPLC; PHOSPHORAMIDON; SQ-28,603 ID ATRIAL-NATRIURETIC-PEPTIDE; EXPERIMENTAL HEART-FAILURE; BINDING-PROPERTIES; GUANYLATE-CYCLASE; RECEPTOR-LIGAND; PLASMA-LEVELS; RATS; INHIBITION; KIDNEY; CELLS AB 1 Urodilatin is a 32 amino-acid peptide of similar sequence to atrial natriuretic peptide (ANP), with four additional amino-acids at the N-terminus. Although ANP and urodilatin bind to the same receptors with similar affinities, urodilatin is more active than ANP as a natriuretic agent. Previous studies, using neutral endopeptidase EC 3.4.24.11 (NEP) derived from crude membrane preparations, were inconclusive, but suggested that urodilatin was more resistant than ANP to degradation by this enzyme. In the present study, we compared the degradation rates of [I-125]-urodilatin and [I-125]-ANP by pure recombinant NEP (rNEP). 2 Incubation of radioactively labelled ANP with rNEP resulted in a much more rapid degradation of the peptide than that for labelled urodilatin. 3 Both phosphoramidon and SQ-28,603, potent inhibitors of NEP, completely protected both peptides from metabolism by rNEP. 4 The circular dichroism spectra of the two peptides indicate that they are very similar and exist largely in unordered or flexible conformations. 5 These results support the relative resistance of urodilatin to NEP, and indicate that urodilatin may be of use as a therapeutic agent, in conditions in which ANP is ineffective. C1 NCI,MED CHEM LAB,BETHESDA,MD 20892. RP ABASSI, ZA (reprint author), NHLBI,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20892, USA. NR 45 TC 9 Z9 9 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD SEP PY 1994 VL 113 IS 1 BP 204 EP 208 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PD641 UT WOS:A1994PD64100032 PM 7812611 ER PT J AU ANDRADE, L EATON, WW CHILCOAT, H AF ANDRADE, L EATON, WW CHILCOAT, H TI LIFETIME COMORBIDITY OF PANIC ATTACKS AND MAJOR DEPRESSION IN A POPULATION-BASED STUDY - SYMPTOM PROFILES SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID CO-MORBIDITY; ANXIETY; CLASSIFICATION; AGORAPHOBIA; CRITERIA; DISORDER; SEVERITY; STATES AB Background. The co-occurrence of panic disorder and major depression in the same individual is common. A question to be answered is whether the comorbid disorder is a distinct one or may resemble one or other disorder. In this paper we examine whether the comorbid disorder is a distinct condition. Method. We examined the symptom profiles and rates of comorbidity of panic attacks and DIS/DSM-III major depressive disorder in a population-based sample from four sites of the National Institute of Mental Health (NIMH) Epidemiologic Catchment Area Program (n = 12 668). Results. The cc-occurrence of panic attacks and major depression over the lifetime was 11 times higher than expected by chance (OR = 11.4, 95% CI 9.5 to 13.6). Subjects with both panic and depression had worse symptoms than those who had only one disorder. However, the pattern of symptoms was remarkably similar, after overall severity was taken into account. Depressive symptoms associated with more severe forms of depression (e.g. guilt, suicidal thoughts or attempts, and motor disturbance) were more frequent in the comorbid group. Conclusions. These findings may indicate a worse severity when the two disorders occur in the same individual. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MENTAL HYGIENE,BALTIMORE,MD. NATL INST DRUG ABUSE,ADDICT RES CTR,BALTIMORE,MD 21224. RI Andrade, Laura/A-1740-2010; Andrade, Laura Helena/F-3023-2010 OI Andrade, Laura Helena/0000-0002-2362-3521 FU NIMH NIH HHS [MH 47447] NR 30 TC 67 Z9 69 U1 3 U2 5 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON, ENGLAND SW1X 8PG SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD SEP PY 1994 VL 165 BP 363 EP 369 DI 10.1192/bjp.165.3.363 PG 7 WC Psychiatry SC Psychiatry GA PE768 UT WOS:A1994PE76800013 PM 7994507 ER PT J AU SHERMAN, A AF SHERMAN, A TI ANTIPHASE, ASYMMETRIC AND APERIODIC OSCILLATIONS IN EXCITABLE CELLS .1. COUPLED BURSTERS SO BULLETIN OF MATHEMATICAL BIOLOGY LA English DT Article ID PANCREATIC BETA-CELLS; BURSTING ELECTRICAL-ACTIVITY; INSULIN RELEASE; MODELS; ISLETS; SYNCHRONIZATION; CHANNELS AB I seek to explain phenomena observed in simulations of populations of gap junction-coupled bursting cells by studying the dynamics of identical pairs. I use a simplified model for pancreatic beta-cells and decompose the system into fast (spike-generating) and slow subsystems to show how bifurcations of the fast subsystem affect bursting behavior. When coupling is weak, the spikes are not in phase but rather are anti-phase, asymmetric or quasi-periodic. These solutions all support bursting with smaller amplitude spikes than the in-phase case, leading to increased burst period. A key geometrical feature underlying this is that the in-phase periodic solution branch terminates in a homoclinic orbit. The same mechanism also provides a model for bursting as an emergent property of populations; cells which are not intrinsic bursters can burst when coupled. This phenomenon is enhanced when symmetry is broken by making the cells differ in a parameter. RP SHERMAN, A (reprint author), NIDDKD,MATH RES BRANCH,BETHESDA,MD 20892, USA. NR 44 TC 69 Z9 69 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0092-8240 J9 B MATH BIOL JI Bull. Math. Biol. PD SEP PY 1994 VL 56 IS 5 BP 811 EP 835 PG 25 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA PE770 UT WOS:A1994PE77000003 PM 7920266 ER PT J AU EANES, ED HAILER, AW AF EANES, ED HAILER, AW TI EFFECT OF ULTRAFILTERABLE FRAGMENTS FROM CHONDROITINASE AND PROTEASE-TREATED AGGRECAN ON CALCIUM-PHOSPHATE PRECIPITATION IN LIPOSOMAL SUSPENSIONS SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE CALCIFICATION; CALCIUM PHOSPHATES; LIPOSOMES; MINERALIZATION; PROTEOGLYCANS ID HYDROXYAPATITE PROLIFERATION; PROTEOGLYCAN INHIBITION; MATRIX VESICLES; CARTILAGE; GROWTH AB A liposome-centered endogenous precipitation method was used to investigate the effect of ultrafilterable fragments from the enzymatic digestion of rat chondrosarcoma aggrecan on the formation of insoluble calcium phosphate salts in buffered solutions at pH 7.4 and 22 degrees C. Unlike the intact aggrecan and its major chondroitin sulfate and core protein components, disaccharide units from chondroitinase degradation of the aggrecan and small (< 3 kg/mol molecular weight) fragments from protease digestion of the core structure were found to be only weakly inhibitory toward mineral formation. Corresponding reductions in Ca2+-binding indicate that these fragments were unable to adsorb to active sites on the apatite surface for long enough periods to significantly hinder crystal growth. The data suggest that controlled enzymatic breakdown of aggrecan may be one possible mechanism by which the calcification of growth plate cartilage is allowed to advance in vivo. RP EANES, ED (reprint author), NATL INST STANDARDS & TECHNOL,NIDR,BONE RES BRANCH,RES ASSOCIATES PROGRAM,BLDG 224,ROOM A143,GAITHERSBURG,MD 20899, USA. NR 20 TC 5 Z9 5 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD SEP PY 1994 VL 55 IS 3 BP 176 EP 179 DI 10.1007/BF00425872 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PC725 UT WOS:A1994PC72500005 PM 7987730 ER PT J AU DERENZO, E AF DERENZO, E TI SURROGATE DECISION-MAKING FOR SEVERELY COGNITIVELY IMPAIRED RESEARCH SUBJECTS - THE CONTINUING DEBATE SO CAMBRIDGE QUARTERLY OF HEALTHCARE ETHICS LA English DT Article ID CLINICAL RESEARCH; INFORMED CONSENT; ETHICS RP DERENZO, E (reprint author), NIH,CTR CLIN,BETHESDA,MD 20892, USA. NR 32 TC 7 Z9 7 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0963-1801 J9 CAMB Q HEALTHC ETHIC JI Camb. Q. Healthc. Ethics PD FAL PY 1994 VL 3 IS 4 BP 539 EP 548 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Social Sciences, Biomedical SC Health Care Sciences & Services; Biomedical Social Sciences GA PX005 UT WOS:A1994PX00500006 PM 7858753 ER PT J AU MACKAY, C AF MACKAY, C TI LIVING-RELATED LIVER-TRANSPLANTATION - COMMENTARY SO CAMBRIDGE QUARTERLY OF HEALTHCARE ETHICS LA English DT Article RP MACKAY, C (reprint author), NIH,BETHESDA,MD 20892, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0963-1801 J9 CAMB Q HEALTHC ETHIC JI Camb. Q. Healthc. Ethics PD FAL PY 1994 VL 3 IS 4 BP 612 EP 621 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Social Sciences, Biomedical SC Health Care Sciences & Services; Biomedical Social Sciences GA PX005 UT WOS:A1994PX00500015 ER PT J AU FIGG, WD COOPER, MR THIBAULT, A HEADLEE, D HUMPHREY, J BERGAN, R REED, E SARTOR, O AF FIGG, WD COOPER, MR THIBAULT, A HEADLEE, D HUMPHREY, J BERGAN, R REED, E SARTOR, O TI ACUTE RENAL TOXICITY ASSOCIATED WITH SURAMIN IN THE TREATMENT OF PROSTATE-CANCER SO CANCER LA English DT Article DE PROSTATE CANCER; SURAMIN; NEPHROTOXICITY; RENAL; ACUTE RENAL FAILURE ID ANTICANCER DRUG; CARCINOMA; THERAPY; TRIAL; AIDS AB The use of suramin, a polysulfonated naphthylurea, in the treatment of advanced prostate cancer currently is being investigated. A 52-year-old man developed acute renal dysfunction after receiving nine doses of suramin. His suramin therapy was discontinued, but his serum creatinine level continued to rise to 10.8 mg/dl during the next 6 days. The patient was not rechallenged with suramin, and his renal function returned to baseline within the next 3 weeks. Future investigators of this drug should be aware of the possibility of such a reaction with parenteral administration. C1 NCI,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. RI Figg Sr, William/M-2411-2016 NR 17 TC 21 Z9 21 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 1994 VL 74 IS 5 BP 1612 EP 1614 DI 10.1002/1097-0142(19940901)74:5<1612::AID-CNCR2820740519>3.0.CO;2-Q PG 3 WC Oncology SC Oncology GA PD349 UT WOS:A1994PD34900018 PM 8062193 ER PT J AU IZRAELI, S ADAMSON, PC BLANEY, SM BALIS, FM AF IZRAELI, S ADAMSON, PC BLANEY, SM BALIS, FM TI ACUTE-PANCREATITIS AFTER IFOSFAMIDE THERAPY SO CANCER LA English DT Article DE PANCREATITIS; IFOSFAMIDE; CHEMOTHERAPY; OSTEOSARCOMA; CASE REPORT AB Acute pancreatitis is an uncommon but serious complication of cancer chemotherapy. A 16-year-old girl with metastatic osteosarcoma experienced recurrent bouts of symptomatic pancreatitis 24 hours after treatment with ifosfamide administered as a single agent. To the authors' knowledge, this is the first report of an association between ifosfamide and pancreatitis. Because serum amylase levels are not monitored routinely during treatment with most chemotherapeutic agents, subclinical cases of pancreatitis with ifosfamide and other agents may go undetected. C1 WALTER REED ARMY MED CTR,DEPT PEDIAT HEMATOL ONCOL,WASHINGTON,DC 20307. RP IZRAELI, S (reprint author), NCI,PEDIAT BRANCH,BLDG 10,ROOM 13N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 6 TC 12 Z9 12 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 1994 VL 74 IS 5 BP 1627 EP 1628 DI 10.1002/1097-0142(19940901)74:5<1627::AID-CNCR2820740522>3.0.CO;2-U PG 2 WC Oncology SC Oncology GA PD349 UT WOS:A1994PD34900021 PM 8062195 ER PT J AU WARD, MH ZAHM, SH WEISENBURGER, DD GRIDLEY, G CANTOR, KP SAAL, RC BLAIR, A AF WARD, MH ZAHM, SH WEISENBURGER, DD GRIDLEY, G CANTOR, KP SAAL, RC BLAIR, A TI DIETARY FACTORS AND NON-HODGKINS-LYMPHOMA IN NEBRASKA (UNITED-STATES) SO CANCER CAUSES & CONTROL LA English DT Article DE ANIMAL PROTEIN; CAROTENES; DIET; MILK; NON-HODGKINS LYMPHOMA; UNITED-STATES; VITAMIN-C AB Little is known about dietary factors and non-Hodgkin's lymphoma (NHL) risk, although high intakes of animal protein and milk have been associated with NHL in two previous studies. As part of a population-based case-control study of agricultural and other risk factors for NHL in eastern Nebraska (USA), we examined the self- and proxy-reported frequency of consumption of 30 food items by 385 White men and women with NHL and 1,432 controls. Animal protein intake was not associated significantly with the risk of NHL, however, there was a nonsignificantly elevated risk of NHL among men with high milk consumption. Vitamin C, carotene, citrus fruit, and dark green vegetable intakes were inversely significantly related to the risk of NHL for men, but not for women. Among men, the odds ratios for the highest quartiles of both vitamin C and carotene intake were 0.6 (95% confidence intervals = 0.3-1.0). There were no meaningful differences in the associations of nutrient intakes and NHL risk between B- and T-cell lymphomas and histologic types. Risks for low intakes of vitamin C and carotene were greater among men and women with a family history of cancer, particularly a history of lymphatic or hematopoietic cancer among first-degree relatives. RP WARD, MH (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EPN ROOM 418,BETHESDA,MD 20892, USA. RI Zahm, Shelia/B-5025-2015 NR 0 TC 108 Z9 108 U1 0 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD SEP PY 1994 VL 5 IS 5 BP 422 EP 432 DI 10.1007/BF01694756 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA PM166 UT WOS:A1994PM16600005 PM 7999964 ER PT J AU INSKIP, PD AF INSKIP, PD TI PELVIC RADIOTHERAPY, SEX-HORMONES, AND BREAST-CANCER SO CANCER CAUSES & CONTROL LA English DT Article DE BREAST CANCER; HORMONES; RADIATION (IONIZING); RADIOTHERAPY AB Radiotherapy for malignant and benign gynecologic disease in middle age has been found to be associated inversely with the risk of breast cancer in several published studies. The ovaries received substantial doses of radiation from such treatments, in the tens of Gray (Gy) from radiotherapy for cervical cancer and one to 10 Gy from radiotherapy for benign gynecologic disease (BGD). The relative risk of breast cancer incidence or mortality decreased with increasing radiation dose to the ovaries between zero to six Gy but varied little with further increases in dose. Evidence of a protective effect even among women irradiated past the age of 50 suggests a mechanism other than that associated with induction of an early menopause. An inverse association with radiotherapy among women over age 50 was seen only for women with ovarian doses exceeding about four to five Gy, namely, those treated for cervical cancer or with external beam X-rays for BGD. Ovarian doses of two to three Gy from intrauterine radium (Ra-226) treatments for BGD were not associated with an appreciably reduced risk of breast cancer, even though the treatments had the intended effect of inducing menopause in women in their mid-40s. The relevant target cells in the ovaries for radiologic menopause likely are those involved in estrogen production. Although the postmenopausal ovary has largely stopped producing estrogens, it continues to secrete androgens. Serum hormone measurements on a small sample of cervical cancer patients indicate that high-dose pelvic radiotherapy eliminates or greatly reduces this residual androgen-producing activity in ovaries of postmenopausal women. Taken together, these observations point to possible differential sensitivity to radiation inactivation of cells in the ovary that produces estrogens and androgens, respectively, and to the possible importance of continued androgen production by the postmenopausal ovary in the etiology or progression of breast cancer. RP INSKIP, PD (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,RADIAT EPIDEMIOL BRANCH,EXECUT PLAZA N,ROOM 408,6130 EXECUT BLVD,ROCKVILLE,MD 20852, USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD SEP PY 1994 VL 5 IS 5 BP 471 EP 478 DI 10.1007/BF01694761 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA PM166 UT WOS:A1994PM16600010 PM 7999969 ER PT J AU VOELLER, DM ALLEGRA, CJ AF VOELLER, DM ALLEGRA, CJ TI INTRACELLULAR METABOLISM OF 5-METHYLTETRAHYDROFOLATE AND 5-FORMYLTETRAHYDROFOLATE IN A HUMAN BREAST-CANCER CELL-LINE SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE 5-METHYL-TETRAHYDROFOLATE; 5-FORMYL-TETRAHYDROFOLATE; ACTIVE FOLATE METABOLITES; THYMIDYLATE SYNTHASE ID THYMIDYLATE SYNTHASE INHIBITION; COLON ADENOCARCINOMA XENOGRAFTS; HIGH-DOSE LEUCOVORIN; FOLATE POOLS; METHOTREXATE; 5-FLUOROURACIL; 5,10-METHYLENETETRAHYDROFOLATE; 5-FLUORO-2'-DEOXYURIDYLATE; FLUOROURACIL; SYNTHETASE AB This report describes the intracellular metabolism of 5-methyltetrahydrofolate (5-methyl-H(4)PteGlu) and 5-formyltetrahydrofolate (5-formyl-H(4)PteGlu) to the various folate forms and their respective polyglutamated states in the MCF-7 human breast-cancer cell lice. The intracellular folate distribution observed in MCF-7 cells treated with 5-methyl-H(4)PteGlu was similar to that seen in cells treated with 5-formyl-H(4)PteGlu. In cells exposed to 5-formyl-H(4)PteGlu for 24 h, the folate pool consisted of 103 +/- 10 pmol/mg 10-formyl-H(4)PteGlu, 120 +/- 18 pmol/mg H(4)PteGlu, and 71 +/- 18 pmol/mg 5-methyl-H(4)PteGlu versus 88 +/- 5, 54 +/- 20 and 87 +/- 10 pmol/mg, respectively, for cells exposed to 5-methyl-H(4)PteGlu. Only the difference seen in H(4)PteGlu levels between cells exposed to either 5-methyl-H(4)PteGlu or 5-formyl-H(4)PteGlu reached statistical significance (P <0.05). In the absence of vitamin B12, exposure to 5-methyl-H(4)PteGlu resulted in 154 +/- 17 pmol/mg 5-methyl-H(4)PteGlu along with only 8 +/- 5 pmol/mg 10-formyl-H(4)PteGlu and 4 +/- 2 pmol/mg H(4)PteGlu, thus demonstrating the marked dependence on vitamin B12 for the metabolism of 5-methyl-H(4)PteGlu to the other intracellular folates. 5-10-Methylene- H(4)PteGlu (2 +/- 1.3 pmol/mg) was detected only in cells exposed to 5-formyl-H(4)PteGlu for 24 h, not in cells treated with 5-methyl-H(4)PteGlu. The profile of polyglutamates detected in cells treated with either 5-formyl-H(4)PteGlu or 5-methyl-H(4)PteGlu for 24 h was not significantly different, although cells treated with 5-methyl-H(4)PteGlu tended to have less conversion to the higher polyglutamates (Glu3-Glu5) as compared with those treated with 5-formyl-H(4)PteGlu. In 5-methyl-H(4)PteGlu-treated cells grown in the absence of vitamin B12, the pentaglutamate was the only polyglutamate form detected, accounting for only 11% of the total folate pool. Since there does not appear to be a greater formation of the optimal reduced-folate forms necessary to achieve enhanced thymidylate synthase (TS) inhibition through ternary-complex formation in cells exposed to 5-methyl-H(4)PteGlu versus 5-formyl-H(4)PteGlu, these studies suggest that the use of 5-methyl-H(4)PteGlu would not be advantageous over that of 5-formyl-H(4)PteGlu in combination regimens with the fluoropyrimidines. C1 NATL NAVAL MED CTR, NCI, MED ONCOL BRANCH, BETHESDA, MD 20889 USA. NR 27 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD SEP PY 1994 VL 34 IS 6 BP 491 EP 496 DI 10.1007/BF00685660 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA PL404 UT WOS:A1994PL40400008 PM 7522978 ER PT J AU ZHAO, L BLOT, WJ LIU, WD CHANG, YS ZHANG, JS HU, YR YOU, WC XU, GW FRAUMENI, JF AF ZHAO, L BLOT, WJ LIU, WD CHANG, YS ZHANG, JS HU, YR YOU, WC XU, GW FRAUMENI, JF TI FAMILIAL PREDISPOSITION TO PRECANCEROUS GASTRIC-LESIONS IN A HIGH-RISK AREA OF CHINA SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID STOMACH-CANCER; MAJOR CANCERS; EPIDEMIOLOGY AB Aggregation of intestinal metaplasia and dysplasia was investigated among families participating in a population-based gastroscopic screening survey in an area of China with one of the world's highest rates of stomach cancer. The prevalence of gastric dysplasia was significantly increased among those with dysplasia among siblings or spouses, but not parents. The odds of dysplasia were nearly doubled if an eldest brother or a spouse was affected. Sibling and spousal associations for intestinal metaplasia were much less pronounced and not statistically significant. The specificity of the findings suggests that familial risk of advanced precancerous lesions (dysplasia) is influenced not only by genetic factors, but also by environmental factors operating in childhood and early adult life. C1 NCI,BIOSTAT BRANCH,EPN 431,6130 EXECUT BLVD,BETHESDA,MD 20892. BEIJING MED UNIV,BEIJING INST CANC RES,BEIJING 100034,PEOPLES R CHINA. LINQU PUBL HLTH BUR,LINQU 262600,PEOPLES R CHINA. WEIFANG MED INST,WEIFANG 261041,PEOPLES R CHINA. WESTAT CORP,ROCKVILLE,MD 20850. FU NCI NIH HHS [N01-CP-95660, N01-CP-15620, N01-CP-05631] NR 12 TC 13 Z9 15 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 1994 VL 3 IS 6 BP 461 EP 464 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA PF475 UT WOS:A1994PF47500002 PM 8000295 ER PT J AU KABUTO, M IMAI, H YONEZAWA, C NERIISHI, K AKIBA, S KATO, H SUZUKI, T LAND, CE BLOT, WJ AF KABUTO, M IMAI, H YONEZAWA, C NERIISHI, K AKIBA, S KATO, H SUZUKI, T LAND, CE BLOT, WJ TI PREDIAGNOSTIC SERUM SELENIUM AND ZINC LEVELS AND SUBSEQUENT RISK OF LUNG AND STOMACH-CANCER IN JAPAN SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NEUTRON-ACTIVATION ANALYSIS; MATCHED CASE-CONTROL; VITAMIN-A; PROSPECTIVE COHORT; TRACE-ELEMENTS; MORTALITY; UPDATE; COPPER; MEN AB Serum samples were collected in Hiroshima and Nagaskai, Japan, from 1970 to 1972 for 208 persons who in 1973-1983 developed stomach cancer; for 77 who in 1973-1983 developed lung cancer; and for controls matched for age, sex, city, and season of blood collection. Average serum levels of selenium and zinc were slightly (<5%) but not significantly lower among the cancer cases than among controls. Smoking-adjusted risks of lung cancer were elevated only among those in the lowest quartiles of serum selenium [odds ratio (OR) = 1.8] and zinc (OR = 1.3); the trends in risk of this cancer with decreasing serum levels were neither linear nor significant. Little or no excess risk of stomach cancer was observed among those with lowest levels of selenium (OR = 1.0) or zinc (OR = 1.2). These exploratory findings add to limited data available from other reports showing slightly increased risks of lung cancer associated with low blood levels of selenium, but suggest little association with either lung or stomach cancer across normal selenium or zinc ranges in this Japanese population. C1 JAPAN NATL INST ENVIRONM STUDIES,TSUKUBA,IBARAKI,JAPAN. JAPAN ATOM ENERGY INST,DEPT RADIAT CHEM,TOKAI,IBARAKI,JAPAN. NATL INST MINAMATA DIS,MINAMATA,KUMAMOTO,JAPAN. KAGOSHIMA UNIV,SCH MED,KAGOSHIMA 890,JAPAN. NCI,BETHESDA,MD 20892. NR 35 TC 60 Z9 63 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 1994 VL 3 IS 6 BP 465 EP 469 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA PF475 UT WOS:A1994PF47500003 PM 8000296 ER PT J AU KATO, SJ SHIELDS, PG CAPORASO, NE SUGIMURA, H TRIVERS, GE TUCKER, MA TRUMP, BF WESTON, A HARRIS, CC AF KATO, SJ SHIELDS, PG CAPORASO, NE SUGIMURA, H TRIVERS, GE TUCKER, MA TRUMP, BF WESTON, A HARRIS, CC TI ANALYSIS OF CYTOCHROME P450-2E1 GENETIC POLYMORPHISMS IN RELATION TO HUMAN LUNG-CANCER SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SUSCEPTIBILITY; DEBRISOQUINE; OXIDATION; RISK; METABOLISM; REGION AB Human cancer risk assessment using molecular genetic techniques is a rapidly emerging field. Many studies suggest that both inherited and acquired genetic predispositions play an important role in carcinogenesis. Cytochrome P450 (CYP) 2E1 is involved in the metabolic activation of N-nitrosamines and other low molecular weight compounds. A recently described genetic polymorphism of CYP2E1 [Dral restriction fragment length polymorphism (RFLP)] has been associated with an increased risk of lung cancer in Japanese. We have assessed the allelic frequency of three RFLPs (Pstl, Rsal, and Dral) in African-Americans (n = 109), Caucasian Americans (n = 153), and octogenarian Japanese (n = 42), and also in a United States case-control study of lung cancer (histologically confirmed lung cancer, n = 58; controls, n = 56; total, n = 114). The relationship of the CYP2E1 Dral Polymorphism to other CYP2E1 polymorphisms (Pstl and Rsal RFLP) was examined. The allelic frequency of the Dral C minor allele for all subjects was 0.09 in Caucasians, 0.09 in African-Americans, and 0.31 in Japanese. In the case-control study of lung cancer, no association of the CYP2E1 Dral genotype with lung cancer was found (odds ratio, 1.57; 95% confidence interval, 0.59-4.18). Comparison after discordant CYP2E1 genotypes suggests the presence of different haplotypes in Americans and Japanese. These results indicate that the CYP2E1 Dral RFLP is probably not a cancer risk factor in United States Caucasian or African-Americans, although statistical power is limited given the low frequency of the CYP2E1 Dral C minor alleles. C1 NCI, DIV CANC ETIOL, GENET EPIDEMIOL BRANCH, BETHESDA, MD 20892 USA. NCI, DIV CANC ETIOL, HUMAN CARCINOGENESIS LAB, BETHESDA, MD 20892 USA. UNIV MARYLAND, DEPT PATHOL, BALTIMORE, MD 21201 USA. HAMAMATSU UNIV SCH MED, DEPT PATHOL, HAMAMATSU, SHIZUOKA 43131, JAPAN. RI Shields, Peter/I-1644-2012; Tucker, Margaret/B-4297-2015 NR 24 TC 73 Z9 74 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 1994 VL 3 IS 6 BP 515 EP 518 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA PF475 UT WOS:A1994PF47500011 PM 8000304 ER PT J AU GROOPMAN, J HARRIS, C HENDERON, B ROSS, R WOGAN, G YU, MM AF GROOPMAN, J HARRIS, C HENDERON, B ROSS, R WOGAN, G YU, MM TI A FOLLOW-UP-STUDY OF URINARY MARKERS OF AFLATOXIN EXPOSURE AND LIVER-CANCER RISK IN SHANGHAI, PEOPLES-REPUBLIC-OF-CHINA - REPLY SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Letter C1 MIT,DIV TOXICOL,CAMBRIDGE,MA 02139. NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. RP GROOPMAN, J (reprint author), JOHNS HOPKINS UNIV,DEPT ENVIRONM HLTH SCI,BALTIMORE,MD 21205, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 1994 VL 3 IS 6 BP 520 EP 521 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA PF475 UT WOS:A1994PF47500013 ER PT J AU MERLO, GR VENESIO, T BERNARDI, A CROPP, CS DIELLA, F CAPPA, APM CALLAHAN, R LISCIA, DS AF MERLO, GR VENESIO, T BERNARDI, A CROPP, CS DIELLA, F CAPPA, APM CALLAHAN, R LISCIA, DS TI EVIDENCE FOR A 2ND TUMOR-SUPPRESSOR GENE ON 17P LINKED TO HIGH S-PHASE INDEX IN PRIMARY HUMAN BREAST CARCINOMAS SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID P53 GENE; SHORT ARM; CELL-PROLIFERATION; HUMAN CANCERS; ALLELE LOSS; HETEROZYGOSITY; MUTATIONS; PROTEIN; CHROMOSOME-17; EXPRESSION AB The short area of chromosome 17 is a frequent target for deletions in human tumors, including breast cancer. We have investigated by restriction fragment polymorphism analysis the pattern of loss of heterozygosity (LOH) at four loci on 17p13.1-17pter in a panel of 110 primary human breast carcinomas. A copy of the p53 gene was lost in 23% of the informative cases. Point mutations in the p53 gene were statistically associated with LOH at the same locus (p = 0.003) but not at other loci on 17p13.3-17pter. A second region bordered by the loci D17S5/D17S28 (17p13.3) and D17S34 (17pter) is also affected by LOH, independent of point mutations in the p53 gene. We propose the presence of a second tumor suppressor gene within this region. In support of this hypothesis is the significant association (p = 0.005) between LOH at the D17S5/D17S28, but not at the TP53 or D17S34 loci, and tumors having a high S-phase index. C1 USSL 1,S GIOVANNI VECCHIO HOSP,ANAT PATHOL SECT,I-10123 TURIN,ITALY. NIH,NATL CANC INST,ONCOGENET SECT,BETHESDA,MD 20892. NR 54 TC 17 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD SEP PY 1994 VL 76 IS 2 BP 106 EP 111 DI 10.1016/0165-4608(94)90458-8 PG 6 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA PL017 UT WOS:A1994PL01700006 PM 7923057 ER PT J AU ANZANO, MA BYERS, SW SMITH, JM PEER, CW MULLEN, LT BROWN, CC ROBERTS, AB SPORN, MB AF ANZANO, MA BYERS, SW SMITH, JM PEER, CW MULLEN, LT BROWN, CC ROBERTS, AB SPORN, MB TI PREVENTION OF BREAST-CANCER IN THE RAT WITH 9-CIS-RETINOIC ACID AS A SINGLE-AGENT AND IN COMBINATION WITH TAMOXIFEN SO CANCER RESEARCH LA English DT Note ID E-CADHERIN EXPRESSION; RETINOIC ACID; CELL-LINES; CARCINOMA; DIFFERENTIATION; METABOLISM; BINDING; TISSUES AB We show that 9-cis-retinoic acid (9cRA) is a potent inhibitor of mammary carcinogenesis induced by N-nitroso-N-methylurea in Sprague-Dawley rats. Rats were first treated with a single dose of N-nitroso-N-methylurea (50 mg/kg body weight) and then fed non-toxic levels of 9cRA (120 or 60 mg/kg of diet). 9cRA was highly effective in reducing tumor incidence, average number of tumors per rat, and average tumor burden, as well as extending tumor latency. The combination of 9cRA with low levels of tamoxifen (TAM; fed at either 1.0 or 0.5 mg/kg of diet) was particularly effective; addition of 9cRA to a TAM regimen doubled the number of animals that were tumor-free at autopsy and significantly diminished tumor number and tumor burden. For suppression of carcinogenesis in vivo, 9cRA was much more potent than all-trans-retinoic acid, both as a single agent or in combination with TAM, although both retinoids had equivalent inhibitory effects on DNA synthesis in cultured human breast cancer cell lines. Both 9cRA and all-trans-retinoic acid induce the expression of the adhesion molecule, E-cadherin, in the SKBR-3 cell line. We suggest that clinical evaluation of the combination of 9cRA and TAM, either for chemoprevention or for adjuvant therapy, should be considered. C1 NCI, BIOMETRY BRANCH, BETHESDA, MD 20892 USA. RP ANZANO, MA (reprint author), NCI, CHEMOPREVENT LAB, BETHESDA, MD 20892 USA. NR 23 TC 200 Z9 203 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 1994 VL 54 IS 17 BP 4614 EP 4617 PG 4 WC Oncology SC Oncology GA PD695 UT WOS:A1994PD69500015 PM 8062253 ER PT J AU JEONG, LS LIM, BB MARQUEZ, VE AF JEONG, LS LIM, BB MARQUEZ, VE TI SYNTHESIS OF A 2,3-DIDEOXY-2,3-DIFLUOROFURANOSE WITH THE D-LYXO CONFIGURATION - AN INTRAMOLECULAR REARRANGEMENT OF METHYL 5-O-BENZOYL-2,3-DIDEOXY-2,3-DIFLUORO-D-LYXOFURANOSIDE OBSERVED DURING THE ATTEMPTED SYNTHESIS OF 1-(2,3-DIDEOXY-2,3-DIFLUORO-BETA-D-LYXOFURANOSYL)THYMINE SO CARBOHYDRATE RESEARCH LA English DT Article DE 2',3'-DIDEOXY-2',3'-DIFLUORO NUCLEOSIDE; FLUORINATION; FLUORO SUGAR; REARRANGEMENT; SYNTHESIS; DIETHYLAMINOSULFUR TRIFLUORIDE ID HUMAN-IMMUNODEFICIENCY-VIRUS; 2',3'-DIDEOXYNUCLEOSIDE ANALOGS; HIV; NUCLEOSIDES; AGENTS AB A new sugar, methyl 5-O-benzoyl-2,3-dideoxy-2,3-difluoro-D-lyxofuranoside (8), which features fluorine substituents on adjacent carbon positions above the plane of the tetrahydrofuran ring, was synthesized from 1,2: 5,6-di-O-isopropylidene-alpha-D-allofuranose in seven steps and 22% overall yield. During the synthesis, introduction of the second fluorine atom required conditions more forceful than those normally used with diethylaminosulfur trifluoride (DAST). An attempt to use 8 in the synthesis of the all-cis nucleoside, 1-(2,3-dideoxy-2,3-difluoro-beta-D-lyxofuranosyl)thymine, failed to give the desired product, providing instead 1-(3-deoxy-3-fluoro-2-O-methyl-beta-D-xylofuranosyl)thymine (11), the structure of which was confirmed by an independent synthesis. Formation of the rearranged product occurred with the concurrent loss of fluorine and retention of the methoxy group which was transposed from the anomeric to the 2'-position. The present work highlights the reactive nature of this novel dideoxydifluoro sugar precursor. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. NR 23 TC 6 Z9 6 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD SEP 1 PY 1994 VL 262 IS 1 BP 103 EP 114 DI 10.1016/0008-6215(94)84007-5 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA PE003 UT WOS:A1994PE00300007 PM 7954518 ER PT J AU WASSERMANN, K OCONNOR, PM JACKMAN, J MAY, A BOHR, VA AF WASSERMANN, K OCONNOR, PM JACKMAN, J MAY, A BOHR, VA TI TRANSCRIPTION-INDEPENDENT REPAIR OF NITROGEN MUSTARD-INDUCED N-ALKYLPURINES IN THE C-MYC GENE IN BURKITTS-LYMPHOMA CA-46 CELLS SO CARCINOGENESIS LA English DT Article ID HAMSTER OVARY CELLS; DNA CROSS-LINKS; PYRIMIDINE DIMERS; DHFR GENE; DAMAGE; REMOVAL; STRAND; METALLOTHIONEIN; PROTOONCOGENE; ACTIVATION AB Recently, it has been demonstrated that N-alkylpurines produced by nitrogen mustard are excised more rapidly from actively transcribing genes compared to non-coding regions of the overall genome. Such studies have suggested that transcriptional activity is a determinant of the rate of removal of these DNA lesions. We have examined the removal of nitrogen mustard-induced N-alkylpurines in the actively transcribed/translocated and transcriptionally repressed native alleles of the c-myc gene in Burkitt's lymphoma, CA46 cells. Burkitt's lymphoma cells, exhibiting a c-myc translocation that can be distinguished from the native allele by Southern blotting, provide a useful model system in which to explore regulatory elements that govern DNA repair in transcriptionally active genes. Northern analysis verified the selective allelic expression of the translocated c-myc gene in CA46 cells. At the drug exposure examined, nitrogen mustard produced a similar level of N-alkylpurines in the two alleles of c-myc. Also, the kinetics of lesion repair from both c-myc alleles over a 24 h repair incubation period was of the same order of magnitude: similar to 34% and similar to 25% of nitrogen mustard-induced N-alkylpurines were removed by 8 h; similar to 72% and similar to 66% of nitrogen mustard lesions were removed by 24 h from the untranslocated and translocated alleles respectively. The untranslocated allele did not become transcriptionally activated upon drug treatment and nitrogen mustard produced a suppression of c-myc message levels from the translocated allele. Therefore, our results suggest that the rate of repair of nitrogen mustard-induced N-alkylpurines is independent of transcriptional activity of the c-myc gene in Burkitt's lymphoma. These findings are discussed in terms of the current views about the mechanisms of gene-specific repair. C1 NCI,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NIA,GENET MOLEC LAB,BALTIMORE,MD 21224. RP WASSERMANN, K (reprint author), NATL INST OCCUPAT HLTH,DEPT TOXICOL & BIOL,LERSO PK ALLE 105,DK-2100 COPENHAGEN,DENMARK. NR 27 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1994 VL 15 IS 9 BP 1779 EP 1783 DI 10.1093/carcin/15.9.1779 PG 5 WC Oncology SC Oncology GA PJ846 UT WOS:A1994PJ84600003 PM 7923569 ER PT J AU TAMANO, S MERLINO, GT WARD, JM AF TAMANO, S MERLINO, GT WARD, JM TI RAPID DEVELOPMENT OF HEPATIC-TUMORS IN TRANSFORMING GROWTH-FACTOR A TRANSGENIC MICE ASSOCIATED WITH INCREASED CELL-PROLIFERATION IN PRECANCEROUS HEPATOCELLULAR LESIONS INITIATED BY N-NITROSODIETHYLAMINE AND PROMOTED BY PHENOBARBITAL SO CARCINOGENESIS LA English DT Article ID FACTOR-ALPHA; RAT-LIVER; C3H/HENCR MICE; C-MYC; MOUSE; HEPATOCARCINOGENESIS; FOCI; DIETHYLNITROSAMINE; OVEREXPRESSION; ONCOGENESIS AB The carcinogenic and tumor-promoting effects of human transforming growth factor alpha (TGF-alpha) overexpression were examined in a two-stage chemical carcinogenesis protocol using TGF-alpha transgenic mouse line MT42. Male MT42 and CD-1 mice received a single i.p. injection of 5 mg N-nitrosodiethylamine (DEN)/kg body wt at 15 days of age, and were placed on a diet containing 0.05% of phenobarbital (PB) from 4 weeks of age for 35 weeks. DEN-, PB-treated and saline-injected animals in each strain were used as controls. A total of three sequential sacrifices (at 10, 23 and 37 experimental weeks) was performed. Hepatocellular carcinomas (HCCs) developed earlier at high incidence (100%) after 23 experimental weeks in MT42 mice receiving DEN/PB, while CD-1 mice had a 40% incidence of HCCs only after week 37. HCCs also developed in the DEN-initiated MT42 mice at 80% incidence after week 23, but no HCCs were observed in the DEN-initiated CD-1 mice. PB induced preneoplastic foci (67%), adenomas (33%) and HCCs (33%) after 37 weeks in MT42 mice, but no lesions were found in CD-1 mice. Thus, the carcinogenic response to DEN and/or PB was accelerated in the MT42 transgenic mice. Furthermore, PB promotion was observed from week 10 in MT42 mice and week 23 in CD-1 mice. Thus, the promoting effect of PB was also accelerated in the MT42 transgenic mice. proliferating cell nuclear antigen (PCNA) labeling indices of hepatocellular foci and adenomas in DEN- or DEN/PB-treated MT42 mice were significantly higher than those of CD-1 mice. TGF-alpha expression determined by immunohistochemistry revealed higher levels in these lesions than in hepatocytes of surrounding parenchyma of MT42 transgenic mice. In conclusion, TGF-alpha transgenic mice clearly demonstrated enhanced sensitivity to the development of hepatocellular carcinoma in the DEN initiation and PB promotion regime, possibly through a mechanism of increased hepatocyte proliferation in precancerous lesions (foci and adenomas), driven by high expression of the mitogen TGF-alpha in these lesions. C1 NCI, OFF LAB ANIM SCI, VET & TUMOR PATHOL SECT, FREDERICK, MD 21702 USA. NCI, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. FU NCI NIH HHS [1-CO-74102] NR 41 TC 47 Z9 47 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1994 VL 15 IS 9 BP 1791 EP 1798 DI 10.1093/carcin/15.9.1791 PG 8 WC Oncology SC Oncology GA PJ846 UT WOS:A1994PJ84600005 PM 7923571 ER PT J AU PENMAN, BW CHEN, LP GELBOIN, HV GONZALEZ, FJ CRESPI, CL AF PENMAN, BW CHEN, LP GELBOIN, HV GONZALEZ, FJ CRESPI, CL TI DEVELOPMENT OF A HUMAN LYMPHOBLASTOID CELL-LINE CONSTITUTIVELY EXPRESSING HUMAN CYP1A1 CDNA - SUBSTRATE-SPECIFICITY WITH MODEL SUBSTRATES AND PROMUTAGENS SO CARCINOGENESIS LA English DT Article ID HUMAN CYTOCHROME-P450 1A1; CHINESE-HAMSTER CELLS; AMINO-ACID SEQUENCE; METABOLIC-ACTIVATION; STABLE EXPRESSION; HUMAN LUNG; XENOBIOTIC METABOLISM; O-DEETHYLASE; HUMAN-LIVER; AFLATOXIN-B1 AB AHH-1 TK+/- cell derivatives were developed that stably express human CYP1A1 cDNA, and an AHH-1 TK+/- derivative expressing higher levels of CYP1A2 cDNA in extrachromosomal vectors which confer resistance to 1-histidinol. The CYP1A1-expressing cell lines, designated h1A1 and h1A1v2 differ by containing one and two CYP1A1 cDNA expression units per vector. The CYP1A2-expressing cell line, designated h1A2v2, also has two CYP1A2 cDNA expression units per vector. Microsomes prepared from CYP1A1 cDNA expressing cells exhibit high, constitutive levels of 7-ethoxyresorufin deethylase (EROD), 7-ethoxycoumarin deethylase (ECD), 7-ethoxy-4-trifluoromethylcoumarin deethylase (EFCD), benzo[a]pyrene hydroxylase (BPH) activities and spectrally quantifiable cytochrome P450. Kinetic comparisons between cDNA-expressed CYP1A1 and CYP1A2 indicate that CYP1A1 is more active than CYP1A1, for EROD, ECD, EFCD and BPH. CYP1A2 was more active than CYP1A1 for acetanilide hydroxylation and activation of affatoxin B-1 (AFB1). The mutagenicity of selected promutagens were examined in h1A1 cells and control cells. Relative to control cells, the h1A1 cell line exhibits increased sensitivity to the mutagenicity of benzo[a]pyrene, cyclopenta[c,d]pyrene, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and AFB(1). C1 GENTEST CORP,WOBURN,MA 01801. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 45 TC 54 Z9 55 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1994 VL 15 IS 9 BP 1931 EP 1937 DI 10.1093/carcin/15.9.1931 PG 7 WC Oncology SC Oncology GA PJ846 UT WOS:A1994PJ84600025 PM 7923587 ER PT J AU SUTTER, C GREENHALGH, DA UEDA, M ABHYANKAR, S NGAI, P HENNINGS, H SCHWEIZER, J YUSPA, SH STRICKLAND, JE AF SUTTER, C GREENHALGH, DA UEDA, M ABHYANKAR, S NGAI, P HENNINGS, H SCHWEIZER, J YUSPA, SH STRICKLAND, JE TI SENCAR MOUSE SKIN TUMORS PRODUCED BY PROMOTION ALONE HAVE A-MUTATION TO G-MUTATION IN CODON-61 OF THE C-RAS(HA) GENE SO CARCINOGENESIS LA English DT Article ID EPIDERMAL-CELL LINES; HARVEY-RAS ONCOGENE; HA-RAS; LIVER-TUMORS; TERMINAL DIFFERENTIATION; CHEMICAL CARCINOGENS; ACTIVATING MUTATIONS; ABERRANT EXPRESSION; SARCOMA-VIRUSES; POINT MUTATION AB SENCAR mice, developed by selective breeding for high susceptibility to skin carcinogenesis by initiation with 7,12-dimethylbenz[a]anthracene and promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA), form squamous papillomas in similar to 20% of animals treated repeatedly with TPA, without chemical initiation. DNA from eight skin tumors produced by a TPA-only protocol and four cell lines derived from these tumors was amplified by polymerase chain reaction and analyzed by discriminative oligonucleotide hybridization using oligomers specific for various c-ras(Ha) gene codon 61 sequences. Five tumors and three cell lines had CAA (wild-type) to CGA mutations. In addition, one tumor had a CAA to CTA mutation, for a total of six of eight tumors having an activating mutation at this codon. Two tumors and one cell line had no codon 61 mutations detectable by this method. Since tumors derived from promotion-only protocols presumably originated from constitutively initiated cells, we examined tumor-free skins of untreated newborn and eight-month-old retired breeders and of 78-88-week-old SENCAR mice of both sexes, which were treated with TPA for 10 weeks starting at age 16-28 weeks and were untreated thereafter. Only the wild-type c-ras(Ha) gene codon 61 sequence was seen, suggesting that the constitutively initiated cell population, if present, is below the limit of detection by this method. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. GERMAN CANC RES CTR,RES PROGRAM 2,W-6900 HEIDELBERG,GERMANY. NR 48 TC 12 Z9 12 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1994 VL 15 IS 9 BP 1975 EP 1978 DI 10.1093/carcin/15.9.1975 PG 4 WC Oncology SC Oncology GA PJ846 UT WOS:A1994PJ84600031 PM 7522983 ER PT J AU BABU, SR LAKSHMI, VM OWENS, IS ZENSER, TV DAVIS, BB AF BABU, SR LAKSHMI, VM OWENS, IS ZENSER, TV DAVIS, BB TI HUMAN LIVER GLUCURONIDATION OF BENZIDINE SO CARCINOGENESIS LA English DT Article ID CARCINOGENIC AROMATIC-AMINES; UDP-GLUCURONOSYLTRANSFERASES; N-GLUCURONIDATION; BLADDER-CANCER; DOG; ACID; RAT AB Although glucuronidation is considered an important pathway in aromatic amine-induced bladder cancer, benzidine glucuronidation has not been assessed in humans. Glucuronidation of benzidine was assessed with human liver microsomes and slices. Emulgen 911-treated microsomes exhibited a K, for benzidine of 0.8+/-0.06 mM and a V-max of 4.2+/-0.7 nmol/mg protein/min. A variety of agents were tested for their ability to inhibit benzidine N-glucuronide formation. At 0.25 mM, estriol, 17-epiestriol, bilirubin, hyodeoxycholic acid and cyproheptadine were good inhibitors (<50% of control). Dose-dependent inhibition studies with estriol, testosterone and 4-aminobiphenyl demonstrated that each agent reached a plateau as its concentration was increased. When these agents were combined at maximal inhibitory concentrations, additive inhibition was observed. These results suggest that more than one UDP-glucuronosyltransferase metabolizes benzidine. The cDNA clones pUDPGT(h)-1 and -2 encode transferases which metabolize hyodeoxycholic acid and estrogen derivatives, but neither transferase catalyzed benzidine glucuronidation. Slices were used to assess metabolism by intact tissue and converted [H-3]benzidine (0.09 mM) to N-acetylbenzidine. N-Glucuronides of both benzidine and N-acetylbenzidine were observed and represented 14-37% of the total recovered radioactivity. The amount of N-acetylbenzidine N'-glucuronide observed was proportional to the amount of N-acetylbenzidine produced. Thus, N-glucuronidation appears to represent a major pathway for metabolism of benzidine in humans. The extent of N-acetylation affects the proportion of benzidine and N-acetylbenzidine glucuronidated by human liver slices. C1 ST LOUIS UNIV,SCH MED,VET ADM MED CTR,DEPT BIOCHEM,ST LOUIS,MO. ST LOUIS UNIV,SCH MED,DIV GERIATR MED,ST LOUIS,MO 63104. NIH,BETHESDA,MD 20892. NR 16 TC 20 Z9 20 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1994 VL 15 IS 9 BP 2003 EP 2007 DI 10.1093/carcin/15.9.2003 PG 5 WC Oncology SC Oncology GA PJ846 UT WOS:A1994PJ84600035 PM 7923596 ER PT J AU ZIEGELSTEIN, RC CHENG, L AVERSANO, T OUYANG, P LAKATTA, EG SILVERMAN, HS AF ZIEGELSTEIN, RC CHENG, L AVERSANO, T OUYANG, P LAKATTA, EG SILVERMAN, HS TI INCREASE IN RAT AORTIC ENDOTHELIAL FREE CALCIUM-MEDIATED BY METABOLICALLY SENSITIVE CALCIUM-RELEASE FROM ENDOPLASMIC-RETICULUM SO CARDIOVASCULAR RESEARCH LA English DT Article DE ENDOTHELIUM; CALCIUM; METABOLISM; CYANIDE; PH ID CYTOSOLIC FREE CALCIUM; INTRACELLULAR CALCIUM; CHEMICAL HYPOXIA; ENERGY DEPLETION; RELAXANT FACTOR; TUBULE CELLS; FREE CA-2+; CORONARY; INHIBITION; ANOXIA AB Objective: The aim was to examine the relationship between cellular metabolism and intracellular [Ca2+] in vascular endothelial cells, focusing on the timing, mechanism. and reversibility of intracellular [Ca2+] changes resulting from ATP depletion. Methods: Cultured rat aortic endothelial monolayers were loaded with indo-1 and exposed for 30 min to: (1) glucose-free buffer, (2) 10 mM deoxyglucose or iodoacetic acid (0.1 or 2.5 mM) to inhibit glycolysis, or (3) 2 mM NaCN to inhibit oxidative phosphorylation with or without glucose. In other experiments, the pH sensitive fluorescent indicator SNARF-1 was used to assess the relationship between observed changes in [Ca2+] and pH. Results: While glucose deprivation resulted in a minor increase in [Ca2+], glycolytic inhibition resulted in a larger, slowly developing, sustained increase in [Ca2+]. Endothelial [Ca2+] was not affected by inhibition of oxidative phosphorylation alone, whereas a rapid, sustained, and largely reversible increase (similar to 102 nM) occurred when NaCN exposure was combined with glucose deprivation. The increase in [Ca2+] during glucose-free NaCN exposure was not altered when calcium influx was prevented by removal of extracellular calcium, but was abolished following depletion of an intracellular calcium store by the endoplasmic reticular Ca2+-ATPase inhibitor thapsigargin. In SNARF-1 loaded monolayers, inhibition of glycolysis with iodoacetic acid decreased intracellular pH by 0.33(SEM 0.10) units whereas inhibition of oxidative phosphorylation in the absence of glucose increased intracellular pH by 0.17(0.05) units. While these divergent pH changes were noted, [Ca2+] increased in both groups. Conclusions: A metabolically sensitive endoplasmic reticular calcium store is rapidly and reversibly released in vascular endothelial cells. Endothelial [Ca2+] is shown to be dependent on glycolytic energy production. In the endothelial cell, brief periods of inhibition of oxidative phosphorylation in the absence of glucose rapidly affect intracellular calcium pools rather than leading to calcium influx due to non-specific cellular damage. Effects on intracellular pH alone cannot account for the changes in [Ca2+]. C1 JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD 21287. NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. RP ZIEGELSTEIN, RC (reprint author), JOHNS HOPKINS BAYVIEW MED CTR,DIV CARDIOL,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 40 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD SEP PY 1994 VL 28 IS 9 BP 1433 EP 1439 DI 10.1093/cvr/28.9.1433 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PK248 UT WOS:A1994PK24800021 PM 7954656 ER PT J AU TAKAHASHI, T EITZMAN, B BOSSERT, NL WALMER, D SPARROW, K FLANDERS, KC MCLACHLAN, J NELSON, KG AF TAKAHASHI, T EITZMAN, B BOSSERT, NL WALMER, D SPARROW, K FLANDERS, KC MCLACHLAN, J NELSON, KG TI TRANSFORMING GROWTH-FACTORS BETA-1, BETA-2, AND BETA-3 MESSENGER-RNA AND PROTEIN EXPRESSION IN MOUSE UTERUS AND VAGINA DURING ESTROGEN-INDUCED GROWTH - A COMPARISON TO OTHER ESTROGEN-REGULATED GENES SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID OSTEOBLAST-LIKE CELLS; IMMATURE RAT UTERUS; TGF-BETA; FACTOR-ALPHA; PERIIMPLANTATION PERIOD; REPRODUCTIVE-TRACT; C-MYC; LIVER-REGENERATION; RIBONUCLEIC-ACID; RECEPTOR AB Increasing evidence suggests that the differential regulation of multiple peptide growth factors by steroid hormones contributes significantly to the pleiotropic effects elicited in target tissues. We report here an evaluation of the effects of the potent estrogen, diethylstilbestrol, on the expression of the three mammalian transforming growth factor beta (TGF beta) isoforms, TGF beta 1, TGF beta 2, and TGF beta 3, in both the uterus and the vagina of the prepubescent mouse. Immunohistochemical protein detection, in situ hybridization, and Northern RNA analyses demonstrate overlapping but distinct time-dependent and site-specific induction of all three TGF beta genes in the reproductive tract in response to estrogen. Temporal analysis of steady-state levels of the TGF beta mRNAs in the uterus by Northern blotting clearly demonstrates that diethylstilbestrol significantly but transiently up-regulates TGF beta 3 mRNA within 30 min and TGF beta 1 and TGF beta 2 mRNAs by 3 h with decreases to/or below control levels by 6 h. The vagina also responds to diethylstilbestrol with similar kinetics of induction for TGF beta 2 and TGF beta 3 mRNAs as that observed in the uterus; however, TGF beta 1 mRNA levels increase gradually and peak around 16 h after treatment. Investigation of the steroid specificity demonstrates predominant estrogen specificity in the control of TGF beta expression in the immature mouse reproductive tract. In situ hybridization localizes the mRN As for all three TGF beta isoforms, primarily to the uterine and vaginal epithelium. Unlike the transient nature of TGF beta mRNA induction elicited by estrogen, immunohistochemistry demonstrates that estrogen treatment results in a more prolonged elevation of the proteins for TGF beta 1, TGF beta 2, and TGF beta 3 in the epithelium of both tissues. Investigation of specific binding of I-125-TGF beta 1 by affinity labeling reveals the existence of the receptor/binding proteins (types I, II, and III) in the uterus. Estrogen treatment significantly reduces binding to each of these components in the uterus, which suggests that estrogen may modulate TGF beta responsiveness at the receptor level. A comparison of TGF beta mRNA expression to the induction of other estrogen-regulated genes, TGF alpha, insulin-like growth factor-1, c-myc, progesterone receptor and lactotransferrin reveals that, in general, the TGF beta transcript levels are regulated in a more transient manner by estrogen. When the induction of these genes is correlated to the growth response measured by 5-bromo-2'-deoxy-uridine incorporation into nuclei, with the exception of lactotransferrin, the mRNA levels for the TGF beta isoforms and the other estrogen-regulated genes are stimulated many hours prior to the initiation of DNA synthesis. These data associate the TGF beta s along with the other genes to a time period at which estrogen is inducing cell cycle transition of the uterine and vaginal epithelium and thus implicating these growth factors in this process. A particular noteworthy finding from our study is that estrogen-mediated vaginal growth involves the regulation of a similar array of peptide growth factors and other genes as documented in the uterus. Morphological studies have documented that the local reaction in the uterus that occurs following estrogen treatment is comparable to an acute inflammatory response, similar to that observed with wounding or tissue trauma. Our data demonstrate that a number of growth factors associated with wound repair, including the TGF beta s, are stimulated by estrogen in the uterus and vagina prior to the initiation of DNA synthesis, which provides further evidence that estrogen mediates its mitogenic action by eliciting a wound healing-like response. C1 NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NR 86 TC 68 Z9 69 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD SEP PY 1994 VL 5 IS 9 BP 919 EP 935 PG 17 WC Cell Biology SC Cell Biology GA PF141 UT WOS:A1994PF14100002 PM 7819129 ER PT J AU WEBSTER, MJ BACHEVALIER, J UNGERLEIDER, LG AF WEBSTER, MJ BACHEVALIER, J UNGERLEIDER, LG TI CONNECTIONS OF INFERIOR TEMPORAL AREAS TEO AND TE WITH PARIETAL AND FRONTAL-CORTEX IN MACAQUE MONKEYS SO CEREBRAL CORTEX LA English DT Review ID LATERAL INTRAPARIETAL AREA; SELECTIVE PREFRONTAL LESIONS; SACCADE-RELATED ACTIVITY; RHESUS-MONKEY; CORTICAL AFFERENTS; MACACA-MULATTA; VISUAL AREA; CORTICOCORTICAL CONNECTIONS; SUPERIOR COLLICULUS; INFANT MONKEYS AB Inferior temporal cortex is perhaps the highest visual processing area and much anatomical work has focused on its connections with other visual areas in temporal and occipital cortex. Here we report connections of inferior temporal cortex with regions in the frontal and parietal lobes. Inferior temporal areas TEO and TE were injected with WGA-HRP and H-3-AA, respectively, or vice versa, in 1-week-old infant and 3-4-year-old adult monkeys ((Macaca mulatta). The results indicated that whereas TEO has more extensive connections with parietal areas, TE has more extensive connections with prefrontal areas. Thus, in the intraparietal sulcus, area TEO is connected with areas LIPd, LIPv, and V3A, and with the as yet undefined region between LIPv and V3A, whereas the connections of TE are predominantly with LIPd, and to a lesser extent with LIPv. In the prefrontal cortex, area TE is connected with areas 8 and 45 in the inferior limb of the anterior bank of the arcuate sulcus, with area 12 on the inferior prefrontal convexity, and with areas 11 and 13 on the orbital surface. By contrast, the connections of area TEO are limited to areas 8, 45, and 12. Furthermore, within prefrontal cortex, the projections from areas TEO and TE terminate in different layers in areas 8 and 45, such that those from TEO terminate in all layers, whereas those from TE terminate in layers I and V/VI only. In contrast to the connections of areas TEO and TE with various medial temporal-lobe and subcortical structures, which are immature in infant monkeys (Webster et al., 1991, 1993b), the connections with parietal and prefrontal areas appear adult-like as early as 1 week of age. RP WEBSTER, MJ (reprint author), NIMH,NEUROPSYCHOL LAB,BLDG 49,ROOM 1B80,BETHESDA,MD 20892, USA. NR 109 TC 349 Z9 350 U1 1 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD SEP-OCT PY 1994 VL 4 IS 5 BP 470 EP 483 DI 10.1093/cercor/4.5.470 PG 14 WC Neurosciences SC Neurosciences & Neurology GA PG018 UT WOS:A1994PG01800004 PM 7530521 ER PT J AU LUESCHOW, A MILLER, EK DESIMONE, R AF LUESCHOW, A MILLER, EK DESIMONE, R TI INFERIOR TEMPORAL MECHANISMS FOR INVARIANT OBJECT RECOGNITION SO CEREBRAL CORTEX LA English DT Article ID INFEROTEMPORAL CORTEX; HIPPOCAMPAL-FORMATION; VISUAL IMAGES; RHINAL CORTEX; TERM-MEMORY; NEURONS; MACAQUE; MONKEYS; ANTERIOR; DISCRIMINATION AB The specific size and retinal location of an object are readily perceived, yet recognition of an object's identity is hardly affected by transformations of its size or location. To explore how such stimulus transformations are treated by known mechanisms for visual short-term memory in inferior temporal (IT) cortex, IT cells were recorded in monkeys performing a delayed matching-to-sample task. The stimuli were pictures of complex objects, and the monkeys ignored differences in size and retinal location when matching the test items to the sample held in memory. The sensory information communicated by cells was assessed in their responses to the sample stimuli, and mnemonic information was assessed in their responses to the test stimuli. In the sensory domain, the ordering of relative stimulus preferences for nearly all cells was invariant over changes in size or location; however, some cells nonetheless preferred stimuli of a given size or location. In the mnemonic domain, the responses of many cells were modulated according to whether the test stimulus matched the sample held in memory, and these memory effects were invariant over the relative sizes and locations of the stimuli. Thus, IT neuronal populations may mediate not only the recognition and memory of object identity, which are invariant over size and location, but also the perception of the transformations themselves. C1 NIMH,NEUROPHYSIOL LAB,BETHESDA,MD 20892. NR 35 TC 106 Z9 107 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD SEP-OCT PY 1994 VL 4 IS 5 BP 523 EP 531 DI 10.1093/cercor/4.5.523 PG 9 WC Neurosciences SC Neurosciences & Neurology GA PG018 UT WOS:A1994PG01800008 PM 7833653 ER PT J AU ROUTLEDGE, MN WINK, DA KEEFER, LK DIPPLE, A AF ROUTLEDGE, MN WINK, DA KEEFER, LK DIPPLE, A TI DNA-SEQUENCE CHANGES INDUCED BY 2 NITRIC-OXIDE DONOR DRUGS IN THE SUPF ASSAY SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID HA-RAS GENE; ESCHERICHIA-COLI; MUTATIONS; CELLS; INDUCTION; INVIVO AB To refine our understanding of the mutational spectra one might expect on exposure of human cells to nitric oxide (NO), we have treated the plasmid pSP189 at pH 7.4 with two compounds that generate NO spontaneously in solution, and then sequenced the mutations found when the treated plasmid was transfected into human Ad293 cells and allowed to replicate. G.C --> A.T transitions were the most abundant mutation observed with these NO donor drugs, whereas in previous work, A.T --> G.C transitions predominated when nitric oxide gas was bubbled through the plasmid solution under otherwise identical conditions. A difference in reactive intermediates formed in solution- versus gas-phase NO exposure was demonstrated by treating buffered 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) or ferrocyanide, in the presence or absence of azide, aerobically with preformed solutions of NO, with solutions of the two NO-releasing compounds, or with gaseous mixtures of equimolar NO/O-2 in air; oxidation of these substrates was extensive with the gas-phase NO source whether azide was present or not, while azide almost completely quenched the oxidation pathway in the solution-phase reactions. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHEM CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,CHEM SECT,FREDERICK,MD 21702. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU NCI NIH HHS [N01-CO-74101] NR 23 TC 75 Z9 75 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD SEP-OCT PY 1994 VL 7 IS 5 BP 628 EP 632 DI 10.1021/tx00041a007 PG 5 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA PJ198 UT WOS:A1994PJ19800007 PM 7841341 ER PT J AU SUGIYAMA, K CORREIA, MA THUMMEL, KE NAGATA, K DARBYSHIRE, JF OSAWA, Y GILLETTE, JR AF SUGIYAMA, K CORREIA, MA THUMMEL, KE NAGATA, K DARBYSHIRE, JF OSAWA, Y GILLETTE, JR TI PH-DEPENDENT ONE-ELECTRON AND 2-ELECTRON OXIDATION OF 3,5-DICARBETHOXY-2,6-DIMETHYL-4-ETHYL-1,4-DIHYDROPYRIDINE CATALYZED BY HORSERADISH-PEROXIDASE SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID N-DEMETHYLATION REACTIONS; LIVER MICROSOMAL CYTOCHROME-P-450; MECHANISM-BASED INACTIVATION; NUCLEAR MAGNETIC-RESONANCE; PROSTHETIC HEME GROUP; ELECTROCHEMICAL OXIDATION; HYDROGEN-PEROXIDE; PHENYLHYDRAZINE; ALKYLHYDRAZINES; DEPROTONATION AB The porphyrinogenic agent 3,5-dicarbethoxy-2,6-dimethyl-4-ethyl-1,4-dihydropyridine (DDEP) is known to inactivate hepatic cytochrome P450 (P450) enzymes 2C11, 2C6, and 3A1 [Correia et al. (1987) Arch. Biochem. Biophys. 258, 436-451] by different mechanisms. The inactivation of P450 2C11 and 2C6 appears to be due to the ethylation of the heme in the active sites of the enzymes [Augusto et al. (1982) J. Biol. Chem. 257, 11288-11295], whereas the inactivation of P450 3A1 appears to involve the covalent binding of the heme to the apoprotein [Correia et al. (1987)]. Moreover, we have found that DDEP inactivates horseradish peroxidase (HRP) pretreated with hydrogen peroxide. In this system, DDEP was oxidized predominately to 3,5-dicarbethoxy-2,6-dimethyl-4-ethylpyridine (EDP) under weakly acidic conditions and predominately to 3,5-dicarbethoxy-2,6-dimethylpyridine (DP) under basic conditions. The loss of heme and the formation of altered heme products were also pH-dependent and were correlated with the formation of DP and the inactivation of HRP. Thus the inactivation of HRP appears to depend on the formation of an ethyl radical, which presumably reacts with the heme in the active site of the enzyme. Similar product ratios were obtained for the oxidation of DDEP by K3Fe(CN)(6), indicating that product ratios of DP over EDP are mainly determined by the pH of buffer. These results, in addition to semiemperical calculations (AM1) for the oxidation of DDEP in the gas phase, are consistent with the idea that the inhibitor undergoes a single-electron oxidation to form the DDEP radical cation, the fate of which depends on the environment of the active site of the enzyme. The proposed formation of a radical cation by the abstraction of an electron from nitrogen is consistent with the finding of low intramolecular isotope effects of the metabolism of 3,5-dicarbethoxy-2,6-dimethyl-[4-H-2,4-H-1]-1,4-dihydropyridine by P450 2C11 and 3A4. Under basic or aprotic conditions, the radical dissociates to form DP and the ethyl radical, which reacts with the heme, thereby inactivating the enzyme. Under acidic or polar conditions, the radical undergoes an additional one-electron oxidation to form EDP. Since DP is the predominant product in P450 2C6- and 2C11-catalyzed reactions [Sugiyama, K., et. al. (1989) Chem. Res. Toxicol. 2, 400-410], these findings suggest that the active sites of P450 2C11 and 2C6 are lipophilic and/or basic. By contrast, P450 3A1 converts DDEP predominately to EDP, suggesting that the active site of this enzyme is polar and/or acidic. C1 NHLBI,CHEM PHARMACOL LAB,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DEPT PHARMACOL,SAN FRANCISCO,CA 94143. UNIV WASHINGTON,DEPT PHARMACEUT,SEATTLE,WA 98195. FU NIDDK NIH HHS [DK-26506] NR 60 TC 2 Z9 2 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD SEP-OCT PY 1994 VL 7 IS 5 BP 633 EP 642 DI 10.1021/tx00041a008 PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA PJ198 UT WOS:A1994PJ19800008 PM 7841342 ER PT J AU LENFANT, C AF LENFANT, C TI REPORT OF THE TASK-FORCE ON RESEARCH IN HEART-FAILURE SO CIRCULATION LA English DT Editorial Material DE CARDIOVASCULAR NEWS; HEART FAILURE ID LEFT-VENTRICULAR HYPERTROPHY; PROGNOSTIC IMPLICATIONS; GENE-EXPRESSION; CARDIOMYOPATHY; DYSFUNCTION; PREVALENCE; MORTALITY; OVERLOAD; ETIOLOGY; CALCIUM RP LENFANT, C (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA. NR 39 TC 50 Z9 59 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 SEP PY 1994 VL 90 IS 3 BP 1118 EP 1123 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PG602 UT WOS:A1994PG60200002 PM 8087921 ER PT J AU COWIE, CC HOWARD, BV HARRIS, MI AF COWIE, CC HOWARD, BV HARRIS, MI TI SERUM-LIPOPROTEINS IN AFRICAN-AMERICANS AND WHITES WITH NON-INSULIN-DEPENDENT DIABETES IN THE US POPULATION SO CIRCULATION LA English DT Article DE DIABETES; LIPOPROTEINS; CHOLESTEROL; RACE ID IMPAIRED GLUCOSE-TOLERANCE; LOW-DENSITY LIPOPROTEIN; CORONARY HEART-DISEASE; UNITED-STATES POPULATION; RISK-FACTORS; TRIGLYCERIDE-METABOLISM; MELLITUS; MORTALITY; PLASMA; PREVALENCE AB Background Despite the significant role that dyslipidemia is believed to play in the development of cardiovascular disease in diabetes, most studies examining diabetic dyslipidemia in the United States have not been population based, and very little data are available for African Americans with diabetes. We used data from a national survey to compare the effect of diabetes on lipid concentrations in African-American and white men and women. In addition, we examined other factors related to lipid concentrations and controlled for these factors in our analyses. Methods and Results The Second National Health and Nutrition Examination Survey included a representative sample of 4177 African Americans and whites in the US civilian noninstitutionalized population 20 to 74 years old. These persons were classified as having non-insulin-dependent diabetes mellitus (NIDDM) (n=720) or as being nondiabetic (n=3457) based on an oral glucose tolerance test and a medical history of diabetes. Subjects were given an interview and physical examination that included measurement of serum lipoproteins, body mass index, body fat distribution, dietary fat intake, alcohol consumption, frequency of smoking, and use of medications. By uivariate analysis, a worse profile of mean cholesterol, triglycerides, and high-density lipoprotein cholesterol levels was generally apparent in NIDDM than in nondiabetic subjects, regardless of race or sex; a similar pattern was found for the prevalence of abnormal concentrations of these lipids. Lipid profiles appeared to be worse in whites with NIDDM than in African Americans. For mean total and low-density lipoprotein cholesterol, concentrations tended to be worse in women with NIDDM than in men. When other factors significantly affecting lipid levels were adjusted by multivariate analysis, we found that in all race/sex groups, total cholesterol was higher in NIDDM than in nondiabetic subjects but differences were not significant (P=.54), triglyceride concentrations were significantly higher in NIDDM subjects (P<.0001), and high-density lipoprotein cholesterol concentrations were lower in NIDDM subjects (P=.003). An interaction of diabetes with race was found for low-density lipoprotein cholesterol (P=.0001), where concentrations were substantially lower in NIDDM than in nondiabetic subjects among African Americans (P<.01) but slightly higher in NIDDM subjects among whites (P=.33). For other lipids, no differential effect of NIDDM was found by race or sex. Conclusions In African-American and white men and women in the United States, NIDDM is associated with a pattern of dyslipidemia that may potentiate the atherosclerotic process. Diabetic treatment should include aggressive treatment of dyslipidemia to reduce this increased risk. C1 MEDLANT RES INST,WASHINGTON,DC. NIDDK,BETHESDA,MD. RP COWIE, CC (reprint author), SOCIAL & SCI SYST INC,7101 WISCONSIN AVE,SUITE 610,BETHESDA,MD 20814, USA. NR 48 TC 47 Z9 48 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP PY 1994 VL 90 IS 3 BP 1185 EP 1193 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PG602 UT WOS:A1994PG60200010 PM 8087927 ER PT J AU FRAKER, DL ALEXANDER, HR THOM, AK AF FRAKER, DL ALEXANDER, HR THOM, AK TI USE OF TUMOR-NECROSIS-FACTOR IN ISOLATED HEPATIC PERFUSION SO CIRCULATORY SHOCK LA English DT Article; Proceedings Paper CT 5th International Congress on TNF and Related Cytokines - Scientific Advances and Their Medical Applications CY MAY 30-JUN 03, 1994 CL MONTEREY, CA DE HEMORRHAGIC NECROSIS; MURINE MODELS; ANTINEOPLASTIC AGENTS; ISOLATED LIMB PERFUSION; MELANOMA ID MALIGNANT-MELANOMA; INTERFERON-GAMMA; COMBINATION; METASTASES; MELPHALAN; ALPHA RP FRAKER, DL (reprint author), NCI,SURG BRANCH,SURG METAB SECT,BLDG 10,ROOM 2B07,BETHESDA,MD 20892, USA. NR 24 TC 31 Z9 31 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0092-6213 J9 CIRC SHOCK JI Circ. Shock PD SEP PY 1994 VL 44 IS 1 BP 45 EP 50 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA QJ723 UT WOS:A1994QJ72300007 PM 7704938 ER PT J AU NAGINENI, CN DETRICK, B HOOKS, JJ AF NAGINENI, CN DETRICK, B HOOKS, JJ TI SYNERGISTIC EFFECTS OF GAMMA-INTERFERON ON INFLAMMATORY MEDIATORS THAT INDUCE INTERLEUKIN-6 GENE-EXPRESSION AND SECRETION BY HUMAN RETINAL-PIGMENT EPITHELIAL-CELLS SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; RETINITIS PIGMENTOSA; MULTIPLE FORMS; UVEITIS; MODULATION; CYTOKINES; ANTIGEN; RETINOBLASTOMA; PROLIFERATION; MONOCYTES AB The retinal pigment epithelial (RPE) cell is a potent regulatory cell within the retina. It helps to maintain normal retinal activity, and following gamma interferon (IFN-gamma) exposure, it may express major histocompatibility complex class II molecules and function as an antigen-presenting cell. Since interleukin-1 (IL-1) and IL-6 are potent cytokines observed in ocular inflammatory processes, we initiated studies to evaluate conditions which enable RPE cells to produce these cytokines. Cultures of human RPE cells from two eye donors were established and characterized, and enzyme immunoassays were employed to screen for IL-1 and IL-6 production. Treatment of RPE cells with lipopolysaccharide (LPS) or recombinant tumor necrosis factor alpha, IL-1, or IFN-gamma resulted in a significant level of secretion of IL-6, In contrast, treatment with recombinant epidermal growth factor, basic fibroblast growth factor, platelet-derived growth factor, or transforming growth factor beta 1 did not result in IL-6 production. IFN-gamma in combination with suboptimal levels of IL-1, tumor necrosis factor alpha, or LPS can dramatically augment the secretion of IL-6 by RPE cells. Thus, these inflammatory mediators can act alone or synergistically with IFN-gamma to activate RPE cells and dramatically increase the expression and secretion of IL-6. In contrast, IL-1 was not detected following stimulation with any of the above-mentioned cytokines or LPS. Characterization of IL-6 protein production by RPE cells revealed that 98% of the protein is promptly secreted by the cell, its induction is dependent upon the time and concentration of the stimulant, and the continuous presence of the stimulant is required for IL-6 production. Moreover, Western blot (immunoblot) analysis of secreted proteins revealed that IL-6 was produced in multiple molecular forms. Characterization of gene transcription by Northern (RNA) blot analysis revealed that mRNA for IL-6 was detected shortly after IL-1 treatment. However, within hours of IL-1 withdrawal, IL-6 mRNA levels returned to control levels. These data demonstrate that LPS and cytokine activation of RPE cells results in the activation of IL-6 gene transcription and IL-6 protein secretion. Moreover, these studies indicate that cytokine activation of RPE cells may be one of the critical factors in ocular inflammation and that it is an important consideration in RPE cell transplantation studies. C1 NEI,IMMUNOL & VIROL SECT,IMMUNOL LAB,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20037. NR 52 TC 49 Z9 49 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD SEP PY 1994 VL 1 IS 5 BP 569 EP 577 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PT566 UT WOS:A1994PT56600014 PM 8556503 ER PT J AU MANN, DL MARTIN, P HAMLINGREEN, G NALEWAIK, R BLATTNER, W AF MANN, DL MARTIN, P HAMLINGREEN, G NALEWAIK, R BLATTNER, W TI VIRUS PRODUCTION AND SPONTANEOUS CELL-PROLIFERATION IN HTLV-I-INFECTED LYMPHOCYTES SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article ID TROPICAL SPASTIC PARAPARESIS; LONG TERMINAL REPEAT; LEUKEMIA-VIRUS; GROWTH-FACTOR; T-CELLS; GENE-EXPRESSION; C RETROVIRUS; CYCLOSPORINE-A; ACTIVATION; MYELOPATHY AB Cultured peripheral blood lymphocytes (PBL) from HTLV-I-infected individuals proliferate in the absence of added mitogens and/or cytokines. In an attempt to answer questions regarding the activating signals for cells and virus, antibodies that react with cell surface components that are known to regulate cell activation and antibodies reacting with viral proteins were added to cultures of PBL from HTLV-I-infected, disease-free individuals. Spontaneous proliferation and virus production increased in the presence of antibodies reacting with CD3 and alpha/beta T cell receptors (TCR) while antibodies to HLA class II and viral proteins had no effect. Addition of HLA class I antibodies shut down virus production and cell proliferation. These observations indicate that both virus and cell activation may occur through the alpha/beta TCR on the infected cell. Cyclosporin A, however, markedly decreased cell proliferation but had only a modest suppressive effect on virus production. Thus, the uncoupling of cell proliferation from virus production by cyclosporin A suggests the possibility that the signal transduction pathways for these two events are different. (C) 1994 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,VIRAL EPIDEMIOL BRANCH,ROCKVILLE,MD 21702. RP MANN, DL (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 55 TC 16 Z9 17 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD SEP PY 1994 VL 72 IS 3 BP 312 EP 320 DI 10.1006/clin.1994.1147 PG 9 WC Immunology; Pathology SC Immunology; Pathology GA PC728 UT WOS:A1994PC72800004 PM 8062446 ER PT J AU KVALE, PA HANSEN, NI MARKOWITZ, N ROSEN, MJ JORDAN, MC MEISELMAN, L GLASSROTH, J REICHMAN, LB WALLACE, JM STANSELL, JD HOPEWELL, PC STANSELL, J TURNER, J OSMOND, D MOSSAR, M HIRSCHTICK, R MANGHISI, KK CARDOZO, C KALB, TH MANGURA, BT BARNES, S SHAPIRO, B LEMAIRE, B RICHER, B AU, J COULSON, A SARAVOLATZ, LD JOHNSON, C HUITSING, J KRYSTOFORSKI, A POOLE, WK RAO, AV CLAYTON, K THOMPSON, J MYERS, D LAVANGE, L KATZIN, J FULKERSON, W GAME, S WILCOSKY, T KALICA, AR WITTES, J FOLLMANN, DA WISE, R AF KVALE, PA HANSEN, NI MARKOWITZ, N ROSEN, MJ JORDAN, MC MEISELMAN, L GLASSROTH, J REICHMAN, LB WALLACE, JM STANSELL, JD HOPEWELL, PC STANSELL, J TURNER, J OSMOND, D MOSSAR, M HIRSCHTICK, R MANGHISI, KK CARDOZO, C KALB, TH MANGURA, BT BARNES, S SHAPIRO, B LEMAIRE, B RICHER, B AU, J COULSON, A SARAVOLATZ, LD JOHNSON, C HUITSING, J KRYSTOFORSKI, A POOLE, WK RAO, AV CLAYTON, K THOMPSON, J MYERS, D LAVANGE, L KATZIN, J FULKERSON, W GAME, S WILCOSKY, T KALICA, AR WITTES, J FOLLMANN, DA WISE, R TI ROUTINE ANALYSIS OF INDUCED SPUTUM IS NOT AN EFFECTIVE STRATEGY FOR SCREENING PERSONS INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS FOR MYCOBACTERIUM-TUBERCULOSIS OR PNEUMOCYSTIS-CARINII SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID IMMUNE-DEFICIENCY SYNDROME; AVIUM-INTRACELLULARE; POSITIVE PATIENTS; PNEUMONIA; DIAGNOSIS; HIV; BACTEREMIA; DISEASE; AIDS AB A prospective multicenter cohort study comprising 1,171 individuals who were seropositive for human immunodeficiency virus (HIV) but did not have AIDS at the time of enrollment and 182 HIV-seronegative controls, was studied by means of routine induced-sputum analysis in an attempt to detect occult tuberculosis or Pneumocystis carinii pneumonia. One occult case of tuberculosis was discovered upon the patient's enrollment (at baseline); none were discovered during follow-up. Two additional Mycobacterium tuberculosis isolates were recovered (one at baseline, one during follow-up) from subjects with symptoms or abnormalities evident on chest roentgenograms. Three specimens were false-positive (one for M tuberculosis, two for P. carinii). Five pathogenic nontuberculous mycobacteria isolates were recovered during follow-up. Nonpathogenic, nontuberculous mycobacteria were recovered from 51 (4.6%) of 1,113 baseline specimens and 56 (3.7%) of 1,518 follow-up specimens, primarily at a center where the water supply was contaminated. We conclude that routine induced-sputum analysis is not an effective strategy for screening HIV-infected asymptomatic subjects for tuberculosis or P. carinii pneumonia before the onset of clinically recognizable disease activity. C1 MT SINAI MED CTR,NEW YORK,NY 10029. NORTHWESTERN UNIV,CHICAGO,IL 60611. UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,NEWARK,NJ 07103. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. RES TRIANGLE INST,CTR DATA COORDINATING,RES TRIANGLE PK,NC 27709. NIAID,BETHESDA,MD. JOHNS HOPKINS UNIV,NHLBI,BALTIMORE,MD 21218. RP KVALE, PA (reprint author), HENRY FORD HOSP,DIV PULM & CRIT CARE MED,2799 W GRAND BLVD,DETROIT,MI 48202, USA. FU PHS HHS [N01-H47-6029, N01-H47-6031, N01-H47-6030] NR 23 TC 9 Z9 10 U1 0 U2 0 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 SEP PY 1994 VL 19 IS 3 BP 410 EP 416 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PG431 UT WOS:A1994PG43100006 PM 7811858 ER PT J AU WALSH, TJ RENSHAW, G ANDREWS, J KWONCHUNG, J CUNNION, RC PASS, HI TAUBENBERGER, J WILSON, W PIZZO, PA AF WALSH, TJ RENSHAW, G ANDREWS, J KWONCHUNG, J CUNNION, RC PASS, HI TAUBENBERGER, J WILSON, W PIZZO, PA TI INVASIVE ZYGOMYCOSIS DUE TO CONIDIOBOLUS-INCONGRUUS SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID RHINOPHYCOMYCOSIS ENTOMOPHTHORAE; CORONATUS INFECTION; NUMERICAL TAXONOMY; PHYCOMYCOSIS; SYSTEMATICS; PATIENT AB During the past decade, an increasing spectrum of pathogenic Zygomycetes fungi have caused infections in humans. The preponderance of these deeply invasive infections have been caused by members of the order Mucorales. However, deeply invasive zygomycoses due to genera of the order Entomophthorales (Conidiobolus species and Basidiobolus species) have seldom been reported. We describe a granulocytopenic patient with pulmonary and pericardial zygomycosis due to Conidiobolus incongruus, describe this organism's susceptibility to antifungal agents, characterize its diagnostic microbiological characteristics, and review previously reported cases of deeply invasive zygomycosis due to Conidiobolus species. In immunocompromised patients, C. incongruus is an uncommon but highly invasive fungal pathogen that may be resistant to amphotericin B and fan be distinguished from other Zygomycetes fungi by characteristic mycological features. C1 NCI,MED BRANCH,BETHESDA,MD 20892. NCI,SURG BRANCH,THORAC ONCOL SECT,BETHESDA,MD 20892. NIAIID,BETHESDA,MD. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT PATHOL,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT CLIN PATHOL,MICROBIOL SERV,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BETHESDA,MD 20892. RP WALSH, TJ (reprint author), NCI,PEDIAT BRANCH,INFECT DIS SECT,BLDG 10,ROOM 13N-240,BETHESDA,MD 20892, USA. NR 33 TC 46 Z9 47 U1 0 U2 0 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 SEP PY 1994 VL 19 IS 3 BP 423 EP 430 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PG431 UT WOS:A1994PG43100008 PM 7811860 ER PT J AU YANOVSKI, JA SOBEL, DO ABBASSI, V AF YANOVSKI, JA SOBEL, DO ABBASSI, V TI THE DIFFERING PRESENTATION OF INSULIN-DEPENDENT DIABETES-MELLITUS IN INFANTS AND CHILDREN SO CLINICAL PEDIATRICS LA English DT Note ID DIAGNOSIS; AUTOANTIBODIES; ONSET; IDDM; AGE C1 GEORGETOWN UNIV,CHILDRENS MED CTR,DIV PEDIAT ENDOCRINOL,WASHINGTON,DC 20007. RP YANOVSKI, JA (reprint author), NICHHD,DEB,DEV ENDOCRINOL SECT,9000 ROCKVILLE PIKE,BLDG 10,ROOM 10N262,BETHESDA,MD 20892, USA. OI Yanovski, Jack/0000-0001-8542-1637 NR 18 TC 3 Z9 3 U1 0 U2 0 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 SN 0009-9228 J9 CLIN PEDIATR JI Clin. Pediatr. PD SEP PY 1994 VL 33 IS 9 BP 556 EP 560 DI 10.1177/000992289403300908 PG 5 WC Pediatrics SC Pediatrics GA PG424 UT WOS:A1994PG42400008 PM 8001325 ER PT J AU MAX, MB AF MAX, MB TI DIVERGENT TRADITIONS IN ANALGESIC CLINICAL-TRIALS SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID PATIENT-CONTROLLED ANALGESIA; PAIN; EFFICACY RP MAX, MB (reprint author), NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BLDG 10,ROOM 3C-405,BETHESDA,MD 20892, USA. NR 24 TC 13 Z9 13 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD SEP PY 1994 VL 56 IS 3 BP 237 EP 241 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PK658 UT WOS:A1994PK65800001 PM 7924116 ER PT J AU SMITH, KA AF SMITH, KA TI THE LISTER-HILL-NATIONAL-CENTER-FOR-BIOMEDICAL-COMMUNICATIONS SO COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE LA English DT Article; Proceedings Paper CT Symposium of the National-Library-of-Medicine and the University-of-Maryland: Information-Services-Division CY APR 07-08, 1994 CL BETHESDA, MD SP NATL LAB MED, MARYLAND UNIV, INFORMAT DIV DE NATIONAL LIBRARY OF MEDICINE; LISTER HILL CENTER; PLANNING PROCESS; DESIGN FEATURES AB On August 3, 1968, the Joint Resolution of the Congress established the program and construction of the Lister Hill National Center for Biomedical Communications. The facility dedicated in 1980 contains the latest in computer and communications technologies. The history, program requirements, construction management, and general planning are discussed including technical issues regarding cabling, systems functions, heating, ventilation, and air conditioning system (HVAC), fire suppression, research and development laboratories, among others. RP SMITH, KA (reprint author), NATL LIB MED,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-2607 J9 COMPUT METH PROG BIO JI Comput. Meth. Programs Biomed. PD SEP PY 1994 VL 44 IS 3-4 BP 201 EP 208 DI 10.1016/0169-2607(94)90114-7 PG 8 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA PP997 UT WOS:A1994PP99700010 PM 7842664 ER PT J AU SNEIDERMAN, C SCHOSSER, R PEARSON, TG AF SNEIDERMAN, C SCHOSSER, R PEARSON, TG TI A COMPARISON OF JPEG AND FIF COMPRESSION OF COLOR MEDICAL IMAGES FOR DERMATOLOGY SO COMPUTERIZED MEDICAL IMAGING AND GRAPHICS LA English DT Article DE COMPRESSION; JPEG; FRACTAL TRANSFORMATION; DISCRETE COSINE TRANSFORMATION; FULL-COLOR IMAGES; DERMATOLOGY AB Dermatologists were shown digitized images of skin lesions compressed by Joint Photographic Expert Group (JPEG) and fractal image format (FIF) algorithms and asked to make a diagnostic assessment and rate the image quality in displaying the features necessary for that assessment. Dermatologists performance in the diagnostic assessment was not affected by the level of compression (up to 40X) using either algorithm, but ratings of image quality for all compressed images were significantly lower than for uncompressed images and for the original photographic slides. There were no significant differences in dermatologists' performance or ratings between the two compression algorithms. C1 UNIV KENTUCKY,SCH MED,DEPT DERMATOL,LEXINGTON,KY 40536. AMER ACAD DERMATOL,DIV EDUC,SCHAUMBURG,IL. UNIV ARKANSAS,COLL MED,FAYETTEVILLE,AR 72701. RP SNEIDERMAN, C (reprint author), NATL LIB MED,LISTER HILL NATL CTR BIOMED COMMUN,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 5 TC 16 Z9 16 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-6111 J9 COMPUT MED IMAG GRAP JI Comput. Med. Imaging Graph. PD SEP-OCT PY 1994 VL 18 IS 5 BP 339 EP 342 DI 10.1016/0895-6111(94)90004-3 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PF023 UT WOS:A1994PF02300004 PM 7954310 ER PT J AU WASENKO, JJ ROSENBAUM, AE YU, SWF FALEN, SW COLLINS, CS AF WASENKO, JJ ROSENBAUM, AE YU, SWF FALEN, SW COLLINS, CS TI GRADIENT-ECHO IMAGING OP THE LUMBAR SPINE SO COMPUTERIZED MEDICAL IMAGING AND GRAPHICS LA English DT Article DE MAGNETIC RESONANCE IMAGING; GRADIENT RECALLED ECHO IMAGING; DISC HERNIATION ID CERVICAL RADICULOPATHY; REFOCUSED-ECHO; DIAGNOSIS; SEQUENCES; DISEASE AB Journal articles have presented pro and con views of gradient recalled echo (GRE) imaging of the lumbar spine, while it has been illustrated in textbooks that have advanced its diagnostic applicability. This paper reappraises GRE in light of evolving MRI technology. The conspicuity of anatomic structures on axial T1-weighted (T1W) spin-echo (SE) images were matched with T2 GRE images in 55 patients referred for evaluation of low back pain. Disc herniations were hyperintense on GRE images and readily separable from hypointense spondylophytes. C1 NIH,DEPT NUCL MED,BETHESDA,MD 20892. MR CT SYRACUSE,SYRACUSE,NY. RP WASENKO, JJ (reprint author), SUNY HLTH SCI CTR,DEPT RADIOL,DIV NEURORADIOL,750 E ADAMS ST,SYRACUSE,NY 13210, USA. NR 17 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-6111 J9 COMPUT MED IMAG GRAP JI Comput. Med. Imaging Graph. PD SEP-OCT PY 1994 VL 18 IS 5 BP 357 EP 365 DI 10.1016/0895-6111(94)90006-X PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PF023 UT WOS:A1994PF02300006 PM 7954312 ER PT J AU LAWRENCE, C AF LAWRENCE, C TI TOWARD THE UNIFICATION OF SEQUENCE AND STRUCTURAL DATA FOR IDENTIFICATION OF STRUCTURAL AND FUNCTIONAL CONSTRAINTS SO COMPUTERS & CHEMISTRY LA English DT Article; Proceedings Paper CT 3rd International Workshop on Open Problems in Computational Molecular Biology CY JUL 11-25, 1993 CL TELLURIDE, CO ID BINDING SITES; EM ALGORITHM; PROTEINS; MODELS AB The identification and characterization of local residue patterns or conserved segments shared by a set of biopolymers has provided a number of insights in molecular biology. Biopolymer sequences are observations from macro molecules that share common structural or function features. The approach taken here rests on the notion that information may be most efficiently extracted from these observations through the use of a model that faithfully represents macro-molecular characteristics. Accordingly, our efforts are focused on statistical models which attempt to capture central features of protein structure, function, and change. Here the assumptions that underlie two new methods for the analysis of protein sequence data are explicitly delineated. (1) Threading of a sequence through structural motifs seeks to determine if a protein sequence fits a known protein structure. The assumptions delineated here also generally apply to other contact based threading methods that have been recently described. (2) Multiple sequence alignment via the Gibbs sampling algorithm seeks to identify position specific empirical free energy models for residue sites in common motifs and simultaneously the align sequence observations form these motifs. C1 NIH,NCBI,BETHESDA,MD 20892. RP LAWRENCE, C (reprint author), NYS DOH,WADSWORTH LABS,ALBANY,NY 12222, USA. NR 26 TC 7 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0097-8485 J9 COMPUT CHEM JI Comput. Chem. PD SEP PY 1994 VL 18 IS 3 BP 255 EP 258 DI 10.1016/0097-8485(94)85021-6 PG 4 WC Chemistry, Multidisciplinary; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA PJ458 UT WOS:A1994PJ45800009 PM 7952896 ER PT J AU WOOTTON, JC AF WOOTTON, JC TI NONGLOBULAR DOMAINS IN PROTEIN SEQUENCES - AUTOMATED SEGMENTATION USING COMPLEXITY-MEASURES SO COMPUTERS & CHEMISTRY LA English DT Article; Proceedings Paper CT 3rd International Workshop on Open Problems in Computational Molecular Biology CY JUL 11-25, 1993 CL TELLURIDE, CO ID EPIDERMAL GROWTH-FACTOR; HEAVY-CHAIN GENE; NUCLEOTIDE-SEQUENCES; FOLDING PATTERNS; LOCAL COMPLEXITY; CORE PROTEIN; MYOSIN ROD; DATA-BANK; PROTEOGLYCAN; CLASSIFICATION AB Computational methods based on mathematically-defined measures of compositional complexity have been developed to distinguish globular and non-globular regions of protein sequences. Compact globular structures in protein molecules are shown to be determined by amino acid sequences of high informational complexity. Sequences of known crystal structure in the Brookhaven Protein Data Bank differ only slightly from randomly shuffled sequences in the distribution of statistical properties such as local compositional complexity. In contrast, in the much larger body of deduced sequences in the SWISS-PROT database, approximately one quarter of the residues occur in segments of non-randomly low complexity and approximately half of the entries contain at least one such segment. Sequences of proteins with known, physicochemically-defined non-globular regions have been analyzed, including collagens, different classes of coiled-coil proteins, elastins, histones, non-histone proteins, mucins, proteoglycan core proteins and proteins containing long single solvent-exposed alpha-helices. The SEG algorithm provides an effective general method for partitioning the globular and non-globular regions of these sequences fully automatically. This method is also facilitating the discovery of new classes of long, non-globular sequence segments, as illustrated by the example of the human CAN gene product involved in tumor induction. RP WOOTTON, JC (reprint author), NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BLDG 38A,ROOM 8N805,BETHESDA,MD 20892, USA. NR 46 TC 290 Z9 302 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0097-8485 J9 COMPUT CHEM JI Comput. Chem. PD SEP PY 1994 VL 18 IS 3 BP 269 EP 285 DI 10.1016/0097-8485(94)85023-2 PG 17 WC Chemistry, Multidisciplinary; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA PJ458 UT WOS:A1994PJ45800011 PM 7952898 ER PT J AU CLAVERIE, JM AF CLAVERIE, JM TI SOME USEFUL STATISTICAL PROPERTIES OF POSITION-WEIGHT MATRICES SO COMPUTERS & CHEMISTRY LA English DT Note ID PATTERNS; ALIGNMENT; SEQUENCES; PROTEIN AB Position-weight matrices (or profiles) are simple mathematical objects traditionally used to capture the information about local sequence patterns (or motifs) characteristic of a given structure or function. Although weight matrices can lead to fast database scanning algorithms their usage has been limited, due to the lack of a reliable method to assess the statistical significance of the matching scores. In this article I first review 3 different computation scheme for designing weight matrices from a block-alignment of any (small or large) number of sequences. I then show that, for patterns spanning 10 positions or more, the best scores expected from matching random sequences are distributed according to the extreme value (Gumbel) distribution. The threshold of statistical significance assessed from this distribution perfectly delineate the range of scores characterizing ''true positive'' sequences (biological significant matches). This result allows weight matrices to be used to scan an entire protein database for patterns in a highly sensitive way. MODEST (MOtif DEsign and Search Tools), a suite of programs in Unix/C, implements these statistical improvements and is available upon E-mail request (jmc(a)ncbi.nlm.nih.gov). RP NIH, NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, 8600 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 13 TC 25 Z9 25 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0097-8485 J9 COMPUT CHEM JI Comput. Chem. PD SEP PY 1994 VL 18 IS 3 BP 287 EP 294 DI 10.1016/0097-8485(94)85024-0 PG 8 WC Chemistry, Multidisciplinary; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA PJ458 UT WOS:A1994PJ45800012 PM 7952899 ER PT J AU OUELLETTE, SC AF OUELLETTE, SC TI STRESS - THE NATURE AND HISTORY OF ENGINEERED GRIEF - KUGELMANN,R SO CONTEMPORARY PSYCHOLOGY-APA REVIEW OF BOOKS LA English DT Book Review C1 NIMH, RES TRAINING PROGRAM HLTH PSYCHOL, WASHINGTON, DC 20032 USA. RP OUELLETTE, SC (reprint author), CUNY, GRAD SCH, NEW YORK, NY 10021 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0010-7549 J9 CONTEMP PSYCHOL JI Comtemp. Psychol. PD SEP PY 1994 VL 39 IS 9 BP 873 EP 874 PG 2 WC Psychology, Multidisciplinary SC Psychology GA PG090 UT WOS:A1994PG09000003 ER PT J AU JOHNSTONE, PAS SINDELAR, WF KINSELLA, TJ AF JOHNSTONE, PAS SINDELAR, WF KINSELLA, TJ TI EXPERIMENTAL AND CLINICAL-STUDIES OF INTRAOPERATIVE RADIATION-THERAPY SO CURRENT PROBLEMS IN CANCER LA English DT Article ID EXTERNAL BEAM IRRADIATION; INTRA-OPERATIVE RADIOTHERAPY; NATIONAL-CANCER-INSTITUTE; SOFT-TISSUE SARCOMAS; PERIPHERAL-NERVE; RETROPERITONEAL; TOLERANCE; CARCINOMA; PANCREAS; IORT AB Intraoperative radiation therapy (IORT) is an innovative treatment modality that has recently been given considerable attention as an approach toward controlling various locally advanced cancers. IORT involves surgical extirpation or debulking of the malignant lesion and the delivery of a large single dose of radiation to the tumor bed or to residual disease. This strategy allows for a theoretical enhancement of the therapeutic effect of radiation for three reasons: (1) the biologic effectiveness of a single large radiation dose is higher than for the same dose given in a fractionated regimen; (2) the dose of radiation is precisely given to the area at greatest risk of tumor recurrence (or persistence); and (3) irradiation of dose-limiting normal tissues may be avoided by operative mobilization of the tissues from the treatment volume by customized lead shielding of anatomically fixed structures or by judicious choice of electron beam energies or use of a bolus to limit dose to deep structures. Electrons are generally used for IORT because of sharp dose falloff. This avoids potential toxic effects to normal structures that may lie deep to the treatment volume. Conventional external beam photon radiation therapy (EBRT) allows less accurate tumor volume delineation (even with sophisticated treatment planning technique) and dose limitations necessitated by normal tissues incidentally in the treatment volume. A considerable amount of experimental and clinical data are available on the acute and late effects of IORT on normal tissues. Dose tolerances of many organs have been described in large animal models, and clinical toxicities are evident in several trials. Clinical IORT treatments are provided in more than 250 U.S. and foreign centers at the present time. Given the current interest in IORT, this monograph will review IORT methods and experimental and clinical results with emphasis on its present and future role for locally advanced cancers. C1 UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. NCI,BETHESDA,MD 20892. UNIV WISCONSIN,DEPT HUMAN ONCOL,MADISON,WI 53706. RP JOHNSTONE, PAS (reprint author), USN,MED CTR,DIV RADIAT ONCOL,SAN DIEGO,CA 92132, USA. NR 90 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 0147-0272 J9 CURR PROB CANCER JI Curr. Probl. Cancer PD SEP-OCT PY 1994 VL 18 IS 5 BP 253 EP 289 PG 37 WC Oncology SC Oncology GA PY654 UT WOS:A1994PY65400001 ER PT J AU KURTZ, A ZIMMER, A SCHNUTGEN, F BRUNING, G SPENER, F MULLER, T AF KURTZ, A ZIMMER, A SCHNUTGEN, F BRUNING, G SPENER, F MULLER, T TI THE EXPRESSION PATTERN OF A NOVEL GENE ENCODING BRAIN FATTY-ACID-BINDING PROTEIN CORRELATES WITH NEURONAL AND GLIAL-CELL DEVELOPMENT SO DEVELOPMENT LA English DT Article DE FATTY ACID BINDING PROTEIN; GENE ISOLATION; RADIAL GLIA; ENSHEATHING CELLS; SATELLITE CELLS; NEUROEPITHELIUM; CNS DEVELOPMENT; MOUSE ID MAMMALIAN NERVOUS-SYSTEM; RETINOIC ACID; GROWTH INHIBITOR; FLOOR PLATE; SPINAL-CORD; DIFFERENTIATION; IDENTIFICATION; INDUCTION; RAT; INVIVO AB Fatty acid binding proteins (FABPs) are a multigene family of small intracellular proteins that bind hydrophobic ligands. In this report we describe the cloning and expression pattern of a novel member of this gene family that is specifically expressed in the developing and adult nervous system and thus was designated brain (B)-FABP. B-FABP is closely related to heart (H)-FABP with 67% amino acid identity. B-FABP expression was first detected at mouse embryonic day 10 in neuroepithelial cells and its pattern correlates with early neuronal differentiation. Upon further development, B-FABP was confined to radial glial cells and immature astrocytes. B-FABP mRNA and protein were found in glial cells of the peripheral nervous system such as satellite cells of spinal and cranial ganglia and ensheathing cells of the olfactory nerve layer from as early as embryonic day 11 until adulthood. In the adult mouse brain, B-FABP was found in the glia limitans, in radial glial cells of the hippocampal dentate gyrus and Bergman glial cells. These findings suggest a function of B-FABP during neurogenesis or neuronal migration in the developing nervous system. The partially overlapping expression pattern with that of cellular retinoid binding proteins suggests that B-FABP is involved in the metabolism of a so far unknown hydrophobic ligand with potential morphogenic activity during CNS development. C1 NIMH,DEV BIOL UNIT,BETHESDA,MD. UNIV MUNSTER,DEPT BIOCHEM,MUNSTER,GERMANY. FREE UNIV BERLIN,DEPT ANAT,W-1000 BERLIN,GERMANY. MAX DELBRUCK CTR MOLEC MED,BERLIN,GERMANY. RI Zimmer, Andreas/B-8357-2009 NR 57 TC 250 Z9 255 U1 0 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 SEP PY 1994 VL 120 IS 9 BP 2637 EP 2649 PG 13 WC Developmental Biology SC Developmental Biology GA PF176 UT WOS:A1994PF17600026 PM 7956838 ER PT J AU POST, RM WEISS, SRB LEVERICH, GS AF POST, RM WEISS, SRB LEVERICH, GS TI RECURRENT AFFECTIVE-DISORDER - ROOTS IN DEVELOPMENTAL NEUROBIOLOGY AND ILLNESS PROGRESSION BASED ON CHANGES IN GENE-EXPRESSION SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Review ID CORTICOTROPIN-RELEASING HORMONE; FOS MESSENGER-RNA; C-FOS; GLUCOCORTICOID RECEPTOR; CONTINGENT TOLERANCE; DEPRESSED-PATIENTS; BIPOLAR DISORDER; TRIGEMINAL NEURALGIA; SLEEP-DEPRIVATION; LIMBIC STRUCTURES AB Electrophysiological kindling and behavioral sensitization to psychomotor stimulants and stress provide paradigms for understanding how repeated acute events can leave neurobiological residues in gene expression, accounting for the observed long-lasting alterations in behavioral responsivity. Kindling helps conceptualize how repeated electrical stimulation of the brain can progressively evoke increased behavioral and convulsive responsivity, leading to spontaneous seizures in the absence of exogenous stimulation following sufficient stimulations. As kindling unfolds, a complex spatiotemporal cascade of events occurs and includes the induction of immediate early genes (e.g., c-fos) and late effector genes (including peptides and growth factors) possible associated with the observed changes in brain microstructure (e.g., synapse formation, axonal and dendritic sprouting, apoptosis). Behavioral sensitization to psychomotor stimulants and stress has also been shown to induce related but different cascades of effects on immediate early and late effector gene expression. These may be associated with the obserbed long-lasting alterations in behavioral responsivity based on prior experience. If these types of alterations are put into a developmental context, this would provide a paradigm for understanding how early life events could exert profound and behaviorally relevant biochemical and microstructural effects on the central nervous system of the developing organism. The conceptual overview offered by the sensitization and kindling models suggests that environmentally triggered neurobiological processes do not form a single or static residue but, instead, engage processes related to developmental neurobiology and learning and memory and whose substrate is constantly evolving over an organism's lifetime. RP POST, RM (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 112 TC 37 Z9 38 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD FAL PY 1994 VL 6 IS 4 BP 781 EP 813 DI 10.1017/S0954579400004788 PG 33 WC Psychology, Developmental SC Psychology GA QF603 UT WOS:A1994QF60300012 ER PT J AU NELSON, T KAUFMAN, EE AF NELSON, T KAUFMAN, EE TI DEVELOPMENTAL TIME COURSES IN THE BRAIN AND KIDNEY OF 2 ENZYMES THAT OXIDIZE GAMMA-HYDROXYBUTYRATE SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article; Proceedings Paper CT Satellite Meeting on Functional Aspects of Energy Metabolism in Neural Tissue CY AUG 28-SEP 01, 1993 CL CARCASSONNE, FRANCE SP INT SOC NEUROCHEM DE ALDEHYDE REDUCTASE; BRAIN; GAMMA-HYDROXYBUTYRATE; GAMMA-HYDROXYBUTYRATE DEHYDROGENASE; HYDROXYACID-OXOACID TRANSHYDROGENASE; KIDNEY ID NADP+-DEPENDENT OXIDOREDUCTASE; RAT-BRAIN; DOPAMINE TURNOVER; PROLACTIN-RELEASE; BETA-ENDORPHIN; GROWTH-HORMONE; NALOXONE; ACID; CATECHOLAMINES; STIMULATION AB The postnatal developmental profiles of two enzymes that oxidize gamma-hydroxybutyrate (GHB) were examined during the period when the brain concentration of GHB was changing from the higher fetal level (7 mu M) to the lower adult level (2 mu M). At 20 days of age, the maximal oxidative capacity (V-max) of GBH dehydrogenase (GHB-D) in the brain reached a rate that was approximately 50% greater than either adult or 18-day fetal values. The V-max for GBH-oxoacid transhydrogenase (GHB-T) in the brain was negligible at 18 days of gestation but increased 40-fold by 20 days and 100-fold by 70 days after birth. In contrast to the brain, the GHB concentration in the kidney remained at approximately 65% of the adult level from birth to 15 days of age and then rose to adult levels. The activities of both GHB-D and GHB-T were 20% of their adult values in the newborn kidney, and both enzymes increased to near adult activities by 20 days. It appears that GHB-D is the predominant catabolic enzyme for GHB in the fetal and neonatal brain, whereas in the kidney both enzymes participate from the earliest time examined. RP NELSON, T (reprint author), NIMH,CEREBRAL METAB LAB,BLDG 36,ROOM 1A-05,BETHESDA,MD 20892, USA. NR 45 TC 10 Z9 10 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PD SEP-DEC PY 1994 VL 16 IS 5-6 BP 352 EP 358 DI 10.1159/000112129 PG 7 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA QL779 UT WOS:A1994QL77900015 PM 7768215 ER PT J AU ROACH, P ZICK, Y FORMISANO, P ACCILI, D TAYLOR, SI GORDEN, P AF ROACH, P ZICK, Y FORMISANO, P ACCILI, D TAYLOR, SI GORDEN, P TI A NOVEL HUMAN INSULIN-RECEPTOR GENE MUTATION UNIQUELY INHIBITS INSULIN BINDING WITHOUT IMPAIRING POSTTRANSLATIONAL PROCESSING SO DIABETES LA English DT Article ID ALPHA-SUBUNIT; GROWTH-FACTOR; CELL-SURFACE; PLASMA-MEMBRANE; TYROSINE KINASE; TRANSPORT; LIGAND; AFFINITY; REGION; SITE AB The precise nature of the insulin-binding site of the insulin receptor (IR) has not been determined, although the importance of several regions of the alpha-subunit in insulin binding has been demonstrated. A naturally occurring mutation in a patient with severe insulin resistance that changes the Ser(323) codon in the alpha-subunit of the IR to a leucine codon is associated with markedly impaired insulin binding to cells from the patient and to transfected cells expressing the mutant receptor. However, unlike other IR alpha-subunit mutations associated with decreased insulin binding, this mutation does not lead to a defect in posttranslational processing or cell-surface expression of IRs. Thus, the defect in insulin binding associated with the Leu(323) mutant IR is a direct result of an alteration in the insulin-binding site. No natural LR mutation described thus far is associated with both decreased insulin binding and normal cell-surface expression of the mutant receptor. This study demonstrates the critical role that Ser(323) Of the IR alpha-subunit plays in insulin binding, either by forming part of the binding site or by stabilizing its conformation. RP ROACH, P (reprint author), NIDDKD,DIABET BRANCH,BLDG 10,ROOM 8S239,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Formisano, Pietro/0000-0001-7020-6870 NR 38 TC 36 Z9 39 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 1994 VL 43 IS 9 BP 1096 EP 1102 DI 10.2337/diabetes.43.9.1096 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PC974 UT WOS:A1994PC97400003 PM 8070609 ER PT J AU SAAD, MF ANDERSON, RL LAWS, A WATANABE, RM KADES, WW CHEN, YDI SANDS, RE PEI, D SAVAGE, PJ BERGMAN, RN AF SAAD, MF ANDERSON, RL LAWS, A WATANABE, RM KADES, WW CHEN, YDI SANDS, RE PEI, D SAVAGE, PJ BERGMAN, RN TI A COMPARISON BETWEEN THE MINIMAL MODEL AND THE GLUCOSE CLAMP IN THE ASSESSMENT OF INSULIN SENSITIVITY ACROSS THE SPECTRUM OF GLUCOSE-TOLERANCE SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; PLASMA-GLUCOSE; RESISTANCE; SECRETION; NIDDM; ATHEROSCLEROSIS; INTOLERANCE; PROTOCOLS; CLEARANCE; DISPOSAL AB An insulin-modified frequently sampled intravenous glucose tolerance test (FSIGTT) with minimal model analysis was compared with the glucose clamp in 11 subjects with normal glucose tolerance (NGT), 20 with impaired glucose tolerance (IGT), and 24 with non-insulin-dependent diabetes mellitus (NlDDM). The insulin sensitivity index (S-I) was calculated from FSIGTT using 22- and 12-sample protocols (S-I(22) and S-I(12), respectively). Insulin sensitivity from the clamp was expressed as S-I(camp) and S-IP(clamp). Minimal model parameters were similar when calculated with S-I((22)) and S-I(12). S-I could not be distinguished from 0 in similar to 50% of diabetic patients with either protocol. S-I(22) correlated significantly with S-I(clamp) in the whole group (r = 0.62), and in the NGT (r = 0.53), IGT (r = 0.48), and NIDDM (r = 0.41) groups (P < 0.05 for each). S-I(12) correlated significantly with S-I(clamp) in the whole group (r = 0.55, P < 0.001) and in the NGT (r = 0.53,P = 0.046) and IGT (r = 0.58, P = 0.008) but not NIDDM (r = 0.30, P = 0.085) groups. When S-I(22), S-I(clamp), and S-IP(clamp) were expressed in the same units, S-I(22) was 66 +/- 5% (mean +/- SE) and 50 +/- 8% lower than S-I(clamp) and S-IP(clamp), respectively. Thus, minimal model analysis of the insulin-modified FSIGTT provides estimates of insulin sensitivity that correlate significantly with those from the glucose clamp. The correlation was weaker, however, in NIDDM. The insulin-modified FSIGTT can be used as a simple test for assessment of insulin sensitivity in population studies involving nondiabetic subjects. Additional studies are needed before using this test routinely in patients with NIDDM. C1 UNIV SO CALIF,SCH MED,DEPT PHYSIOL & BIOPHYS,LOS ANGELES,CA 90033. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. STANFORD UNIV,SCH MED,DEPT MED,STANFORD,CA. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. RP SAAD, MF (reprint author), UNIV SO CALIF,SCH MED,DEPT MED,DIV DIABET,1200 N STATE ST,UNIT 1,ROOM 8250,LOS ANGELES,CA 90033, USA. FU NHLBI NIH HHS [HL-08506, HL-47887, HL-47902] NR 40 TC 325 Z9 334 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 1994 VL 43 IS 9 BP 1114 EP 1121 DI 10.2337/diabetes.43.9.1114 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PC974 UT WOS:A1994PC97400006 PM 8070611 ER PT J AU RAVUSSIN, E BENNETT, PH VALENCIA, ME SCHULZ, LO ESPARZA, J AF RAVUSSIN, E BENNETT, PH VALENCIA, ME SCHULZ, LO ESPARZA, J TI EFFECTS OF A TRADITIONAL LIFE-STYLE ON OBESITY IN PIMA-INDIANS SO DIABETES CARE LA English DT Article ID DEPENDENT DIABETES-MELLITUS; BODY-MASS INDEX; PHYSICAL-ACTIVITY; TWINS; DETERMINANTS; CONSUMPTION; ADOPTION; DISEASE; WEIGHT; FAT AB OBJECTIVE- The Pima Indians of Arizona have the highest reported prevalences of obesity and non-insulin-dependent diabetes mellitus (NIDDM). In parallel with abrupt changes in lifestyle, these prevalences in Arizona Pimas have increased to epidemic proportions during the past decades. To assess the possible impact of the environment on the prevalences of obesity and NIDDM, data were collected on members of a population of Pima ancestry (separation 700-1,000 years ago) living in a remote mountainous location in northwestern Mexico, with a lifestyle contrasting markedly with that in Arizona. RESEARCH DESIGN AND METHODS- Pima heritage was established by history and by use of Pima language. Measurements of weight, height, body fat (bioimpedance), blood pressure, plasma levels of glucose, cholesterol, and HbA(1c) were obtained in 19 women (36 +/- 13 years of age) and 16 men (48 +/- 14 years of age) and compared with sex-, age- and diabetes status-matched Pimas living in Arizona (10 Arizona Pimas for each Mexican Pima). RESULTS- Mexican Pimas were lighter (64.2 +/- 13.9 vs. 90.2 +/- 21.1 kg, P < 0.0001;means +/- SD) and shorter (160 +/- 8 vs. 164 +/- 8 cm, P < 0.01) with lower body mass indexes (24.9 +/- 4.0 vs. 33.4 +/- 7.5 kg/m(2), P < 0.0001) and lower plasma total cholesterol levels (146 +/- 30 vs. 174 +/- 31 mg/dl, P < 0.0001) than Arizona Pimas. Only two women (11%) and one man (6%) had NIDDM, contrasting with the expected prevalences of 37 and 54% in female and male Arizona Pimas, respectively. CONCLUSIONS- This preliminary investigation shows that obesity, and perhaps NIDDM, is less prevalent among people of Pima heritage living a ''traditional'' lifestyle than among Pimas living in an ''affluent'' environment. These findings suggest that, despite a similar potential genetic predisposition to these conditions, a traditional lifestyle, characterized by a diet including less animal fat and more complex carbohydrates and by greater energy expenditure in physical labor, may protect against the development of cardiovascular disease risk factors, obesity, and NIDDM. C1 CTR INVEST ALIMENTAC & DESARROLLO,DIV NUTR,HERMOSILLO,SONORA,MEXICO. UNIV WISCONSIN,DEPT HLTH SCI,MILWAUKEE,WI 53201. RP RAVUSSIN, E (reprint author), NIDDKD,CLIN DIABET & NUTR SECT,4212 N 16TH ST,ROOM 541,PHOENIX,AZ 85016, USA. NR 47 TC 215 Z9 220 U1 2 U2 17 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD SEP PY 1994 VL 17 IS 9 BP 1067 EP 1074 DI 10.2337/diacare.17.9.1067 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PD088 UT WOS:A1994PD08800021 PM 7988310 ER PT J AU GRIGIONI, WF DERRICO, A FIORENTINO, M BACCARINI, P ONISTO, M CAENAZZO, C STETLERSTEVENSON, WG GARBISA, S MANCINI, AM AF GRIGIONI, WF DERRICO, A FIORENTINO, M BACCARINI, P ONISTO, M CAENAZZO, C STETLERSTEVENSON, WG GARBISA, S MANCINI, AM TI GELATINASE-A (MMP-2) AND ITS MESSENGER-RNA DETECTED IN BOTH NEOPLASTIC AND STROMAL CELLS OF TUMORS WITH DIFFERENT INVASIVE AND METASTATIC PROPERTIES SO DIAGNOSTIC MOLECULAR PATHOLOGY LA English DT Article DE TUMOR INVASION; GELATINASE A; METALLOPROTEINASE ID COLLAGENASE-STIMULATORY FACTOR; BASEMENT-MEMBRANE COLLAGEN; IV COLLAGENASE; COLON CANCER; EXPRESSION; FIBROBLASTS; CARCINOMA; METALLOPROTEINASE; DEGRADATION; INHIBITOR AB Simultaneous presence of gelatinase A (MMP-2) and MMP-2 messenger RNA (mRNA) in 30 malignant tumors with various degrees of differentiation and biological behavior was evaluated by immunohistochemistry and in situ hybridization. The series consisted of 10 gastric carcinomas, 10 colorectal carcinomas, five squamous skin carcinomas, and five basal cell skin tumors. MMP-2 was detected in all cases. MMP-2 mRNA was expressed in the stromal cells in all cases and was more marked in the less-differentiated gastric and colonic carcinomas; it was also detected in the neoplastic cells of poorly differentiated tumors, particularly in those of the signet-ring cell type, both in the colon and stomach. The study confirmed that stromal cells have a specific role in tumor invasion and suggests a direct relationship between neoplastic epithelium and stromal cells in the most aggressive varieties. C1 UNIV PADUA,INST HISTOL & GEN EMBRYOL,PADUA,ITALY. NIH,PATHOL LAB,BETHESDA,MD 20892. RP GRIGIONI, WF (reprint author), UNIV BOLOGNA,IST ANAT PATOL,VIA MASSARENTI 9,I-40138 BOLOGNA,ITALY. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 28 TC 36 Z9 40 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1052-9551 J9 DIAGN MOL PATHOL JI Diagn. Mol. Pathol. PD SEP PY 1994 VL 3 IS 3 BP 163 EP 169 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology GA PC618 UT WOS:A1994PC61800005 PM 7981891 ER PT J AU HEYDEN, A LUTZOWHOLM, C CLAUSEN, OPF THRANE, EV BRANDTZAEG, P ROOP, DR YUSPA, SH HUITFELDT, HS AF HEYDEN, A LUTZOWHOLM, C CLAUSEN, OPF THRANE, EV BRANDTZAEG, P ROOP, DR YUSPA, SH HUITFELDT, HS TI APPLICATION OF CANTHARIDIN OR 12-O-TETRADECANOYLPHORBOL-13-ACETATE ON MOUSE EPIDERMIS INDUCES A CELL-POPULATION SHIFT THAT CAUSES ALTERED KERATIN DISTRIBUTION SO DIFFERENTIATION LA English DT Article ID PROTEIN-KINASE-C; TUMOR PROMOTER 12-O-TETRADECANOYLPHORBOL-13-ACETATE; 2-STAGE CHEMICAL CARCINOGENESIS; HISTIDINE-RICH PROTEIN; GENE-EXPRESSION; BASAL CELLS; REGENERATIVE PROLIFERATION; TERMINAL DIFFERENTIATION; PHORBOL ESTER; SKIN AB The tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) causes changes in epidermal protein expression, especially in the major differentiation products keratins K1 and K10. These keratins and filaggrin were studied in a pulse-labelled cell cohort in hairless mouse epidermis stimulated to proliferate by TPA or the hyperplasiogen cantharidin. Cells in DNA synthesis were pulse-labelled by 5-bromo-2-deoxyuridine (BrdU) 16h after topical application of cantharidin or TPA. The BrdU-labelled cell cohort, the two keratins, and filaggrin were spatially mapped by paired immunofluorescence staining. Both cantharidin- and TPA-treated epidermis displayed altered distributions of K1 and K10 with expression only in the outermost cell layers, but the start of their postreplicative expression parallelled that in normal epidermis (18 h for K1 and 24 h for K10 after the last round of DNA synthesis). Cantharidin- and TPA-induced epidermal hyperplasia showed increased basal cell proliferation, accelerated suprabasal migration, and shortened transit time. Thus, the newly formed hyper-plastic epidermis was composed of keratinocytes with a lower mean cellular age than that seen in unperturbed epidermis, which caused altered distribution of K1 and K10. Both hyperplastic and normal epidermis showed filaggrin expression in stratum granulosum; this started earlier in treated (30-36 h) than in untreated (96 h) skin. We concluded that the postmitotic onset of K1 and K10 expression was unaltered in regenerative epidermis, whereas filaggrin expression was considerably accelerated and thus influenced by the cell kinetic changes. C1 UNIV OSLO,NATL HOSP,RIKSHOSP,INST PATHOL,N-0027 OSLO,NORWAY. NATL INST PUBL HLTH,N-0462 OSLO,NORWAY. BAYLOR COLL MED,DEPT CELL BIOL & DERMATOL,HOUSTON,TX 77030. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT,BETHESDA,MD 20892. RP HEYDEN, A (reprint author), UNIV OSLO,FAC DENT,DEPT ORAL SURG & ORAL MED,POB 1109,BLINDERN,N-0317 OSLO,NORWAY. NR 41 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0301-4681 J9 DIFFERENTIATION JI Differentiation PD SEP PY 1994 VL 57 IS 3 BP 187 EP 193 DI 10.1046/j.1432-0436.1994.5730187.x PG 7 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA PH534 UT WOS:A1994PH53400005 PM 7527355 ER PT J AU JI, XD VONLUBITZ, D OLAH, ME STILES, GL JACOBSON, KA AF JI, XD VONLUBITZ, D OLAH, ME STILES, GL JACOBSON, KA TI SPECIES-DIFFERENCES IN LIGAND AFFINITY AT CENTRAL A(3)-ADENOSINE RECEPTORS SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE XANTHINES; GERBIL; RABBIT; RADIOLIGAND BINDING; ADENOSINE ANALOGS ID ADENOSINE RECEPTOR; MOLECULAR-CLONING; MAMMALIAN BRAIN; ANTAGONISTS; INHIBITION; EXPRESSION; AGONISTS; CDNA; RAT AB Binding affinities of purine derivatives at A(3) adenosine receptors in different species were compared. Binding was carried out using the novel high affinity agonist ligand [I-125]AB-MECA (3-iodo-4-aminobenzyladenosine-5'-N-methyluronamide) in the presence of 1.0 mu M XAC (8-[4-[[[[(2-aminoethyl)amino]carbonyl]methyl]oxy]phenyl]-1,3-dipropylxanthine), an A(1)- and A(2a)-adenosine antagonist. XAC was added to eliminate binding to non-A(3) receptors. In rat brain membranes [I-125]AB-MECA exhibited saturable, specific binding with a K-d of 2.28 nM and a B-max of 43 fmol/mg protein. The affinity of [I-125]AB-MECA at the gerbil and rabbit brain A(3)-receptors was similar to the rat, suggesting that the affinity of this agonist is not highly species dependent. The affinity of various xanthine derivatives was measured in [I-125]AB-MECA competition binding assays. Gerbil and rabbit brain A(3)-receptors were similar in the affinity of antagonists whose potency order in both species was: BWA522 greater than or equal to CPX > XCC, XAC, SPX, BWA1433 > theophylline. The affinities of 8-arylxanthines at the rat, rabbit, and gerbil brain A(3) receptors were considerably less than the previously reported affinities at cloned sheep and human A(3) receptors. Species differences in agonist affinity were assessed by comparing K-i values at cloned rat brain A(3) receptors expressed in CHO cells with cloned sheep and human A(3) receptors. Human and rat brain A(3) receptors were highly similar in the relative affinities of agonists, and sheep brain A(3) receptors were unlike either human or rat A(3) receptors in agonist affinity. (C) 1994 Wiley-Liss, Inc. C1 NIDDKD,BIOORGAN CHEM LAB,MOLEC RECOGNIT SECT,BETHESDA,MD. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC. DUKE UNIV,MED CTR,DEPT PHARMACOL,DURHAM,NC. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 28 TC 75 Z9 77 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 SEP PY 1994 VL 33 IS 1 BP 51 EP 59 DI 10.1002/ddr.430330109 PG 9 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PH284 UT WOS:A1994PH28400008 ER PT J AU BUTERS, JTM KORZEKWA, KR KUNZE, KL OMATA, Y HARDWICK, JP GONZALEZ, FJ AF BUTERS, JTM KORZEKWA, KR KUNZE, KL OMATA, Y HARDWICK, JP GONZALEZ, FJ TI CDNA-DIRECTED EXPRESSION OF HUMAN CYTOCHROME-P450 CYP3A4 USING BACULOVIRUS SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID HUMAN-LIVER; CATALYTIC ACTIVITIES; VACCINIA VIRUS; METABOLISM; IDENTIFICATION; OXIDATION; REDUCTASE; PHARMACOKINETICS; HYDROXYLATION; POLYMORPHISM AB A recombinant baculovirus containing the human CYP3A4 cDNA was constructed and used to express CYP3A4 in SF9 insect cells (0.46 +/- 0.13 nmol/mg protein, 103 +/- 29 nmol/liter, N = 15). The enzyme represented similar to 2-3% of total cellular protein and could be purified by a two column procedure to a specific content of 12.7 nmol/mg protein. Catalytic activity of the purified enzyme after reconstitution was optimum using molar ratios of CYP3A4 to cytochrome b(5) to NADPH-P450 oxidoreductase of 1:3:20, respectively. The enzyme metabolized cortisol, erythromycin, testosterone, and (R)-warfarin. Recombinant baculovirus expresses the highest amounts of all expression systems published to date of catalytically intact CYP3A4. This system is an excellent alternative for the isolation and characterization of P450 forms from human liver. C1 WASHINGTON UNIV,MED CHEM LAB,ST LOUIS,MO 63130. NE OHIO UNIV,ROOTSTOWN,OH 44272. RP BUTERS, JTM (reprint author), NCI,BLDG 37,ROOM 3E24,BETHESDA,MD 20892, USA. RI Buters, Jeroen/G-5070-2011 NR 36 TC 78 Z9 80 U1 0 U2 4 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 SEP-OCT PY 1994 VL 22 IS 5 BP 688 EP 692 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PJ513 UT WOS:A1994PJ51300004 PM 7835218 ER PT J AU MALOW, BA REESE, KB SATO, S BOGARD, PJ MALHOTRA, AK SU, TP PICKAR, D AF MALOW, BA REESE, KB SATO, S BOGARD, PJ MALHOTRA, AK SU, TP PICKAR, D TI SPECTRUM OF EEG ABNORMALITIES DURING CLOZAPINE TREATMENT SO ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE CLOZAPINE; EEG; MYOCLONUS; EPILEPTIFORM ABNORMALITIES ID SEIZURES; SCHIZOPHRENIA; THERAPY AB Clozapine is a novel antipsychotic agent effective in treating refractory schizophrenia. Clozapine produces fewer extrapyramidal effects than other neuroleptics, although agranulocytosis and seizures are significant adverse effects. To characterize the spectrum of clozapine-related electroencephalographic abnormalities, we identified 10 patients who had electroencephalograms (EEGs) performed before and during clozapine treatment. These 10 patients represented a subset of individuals participating in an investigational trial. During clozapine treatment, five developed myoclonus and one experienced a generalized tonic-clonic seizure. Records were retrospectively reviewed by an electroencephalographer blinded to the patient's history and medications. All patients had normal EEGs before clozapine treatment. While receiving clozapine (250-900 mg daily), all patients developed background slowing in the theta and often delta ranges. Additionally, 7 patients exhibited bilateral spike, polyspike and slow wave discharges, one with a photoparoxysmal response. Follow-up EEGs performed in 4 of these 7 patients after a decrease in clozapine dosage and/or addition in valproic acid showed diminished epileptiform activity. C1 NINCDS,EEG SECT,BETHESDA,MD 20892. NIMH,EXPTL THERAPEUT BRANCH,BETHESDA,MD. MAINE MED CTR,DEPT PSYCHIAT,PORTLAND,ME. NR 21 TC 47 Z9 47 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0013-4694 J9 ELECTROEN CLIN NEURO JI Electroencephalogr. Clin. Neurophysiol. PD SEP PY 1994 VL 91 IS 3 BP 205 EP 211 DI 10.1016/0013-4694(94)90070-1 PG 7 WC Engineering, Biomedical; Clinical Neurology SC Engineering; Neurosciences & Neurology GA PG745 UT WOS:A1994PG74500007 PM 7522149 ER PT J AU HINTERBERG, K MATTEI, D WELLEMS, TE SCHERF, A AF HINTERBERG, K MATTEI, D WELLEMS, TE SCHERF, A TI INTERCHROMOSOMAL EXCHANGE OF A LARGE SUBTELOMERIC SEGMENT IN A PLASMODIUM-FALCIPARUM CROSS SO EMBO JOURNAL LA English DT Article DE DUPLICATIVE TRANSPOSITION; GENETIC CROSS; MALARIA; PF332 AND RESA-2 GENES; SUBTELOMERIC RECOMBINATION ID CHROMOSOME SIZE POLYMORPHISM; REPEAT SEQUENCES; SQUIRREL-MONKEY; GENETIC CROSS; P-FALCIPARUM; TELOMERE; DNA; RECOMBINATION; PROTEIN; MALARIA AB Duplications and interchromosomal transpositions of chromosome segments are implicated in the genetic variability of Plasmodium falciparum malaria parasites. One parasite clone, HB3, was shown to lack a subtelomeric region of chromosome 13 that normally carries a PfHRPIII gene. We show here that the chromosome 13 segment carrying PfHRPIII was replaced in HB3 by a duplicated terminal segment from chromosome 11. Mapping results indicate that the segment includes at least 100-200 kb of subtelomeric DNA and contains duplicated copies of the Pf332 and RESA-2 genes. We followed inheritance of this duplication in a genetic cross between the HB3 and another P.falciparum clone, Dd2, that is euploid for the Pf332, RESA-2 and PfHRPIII genes. Three types of progeny from the cross showed expected inheritance forms: a Dd2 euploid parent type, an HB3 aneuploid parent type, and a recombinant euploid type that carried PfHRPIII from Dd2 chromosome 13 and Pf332 from HB3 chromosome 11. However, a fourth euploid progeny type was also observed, in which the chromosome 13 segment from HB3 was transposed back to replace the terminus of chromosome 11. Three of 14 individual progeny were of this type. These findings suggest a mechanism of recombination from subtelomeric pairing and exchange between non-homologous chromosomes in meiosis. C1 INST PASTEUR,UNITE PARASITOL EXPTL,CNRS,URA 361,F-75724 PARIS,FRANCE. NIH,MALARIA RES LAB,BETHESDA,MD 20892. RI Scherf, Artur/A-9674-2014; Mattei, Denise/B-1088-2014 NR 50 TC 48 Z9 50 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 SEP 1 PY 1994 VL 13 IS 17 BP 4174 EP 4180 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PF606 UT WOS:A1994PF60600028 PM 8076613 ER PT J AU FRIEDMAN, TC LOH, YP BIRCH, NP AF FRIEDMAN, TC LOH, YP BIRCH, NP TI IN-VITRO PROCESSING OF PROOPIOMELANOCORTIN BY RECOMBINANT PC1 (SPC3) SO ENDOCRINOLOGY LA English DT Article ID OPIOMELANOCORTIN-CONVERTING ENZYME; PITUITARY INTERMEDIATE LOBE; FUNCTIONAL EXPRESSION; PROPROTEIN CONVERTASE; ENDOPROTEASE FAMILY; SECRETORY VESICLES; ASPARTIC PROTEASE; SERINE PROTEASE; CDNA STRUCTURE; RAT PITUITARY AB The prohormone convertases, PC1 (SPC3) and PC2, are subtilisin-like serine proteases capable of processing neuropeptide precursors. In cotransfection experiments, other investigators have found that PC1 and PC2 can process POMC to appropriate peptide products. In this study, recombinant rat PC1 was stably expressed in a mouse L-cell line and partially purified. Mouse POMC was cleaved by recombinant PC1 to generate ACTH intermediates, ACTH, ACTH linked to joining peptide, joining peptide, 16-kilodalton N-POMC, N-POMC-(1-74), and beta-lipotropin. Recombinant PC1 was also found to cleave ACTH to ACTH-(1-15) and bovine N-POMC-(1-77) to gamma(3)MSH. The pH optimum of the cleavages was 6.0. We conclude that recombinant PC1 is capable of processing POMC in vitro at all of the paired basic residues, with the exception of Lys-Arg and Lys-Lys in beta-lipotropin and beta-endorphin, respectively. This in vitro study showed a more general specificity of recombinant PC1 for paired and tetrabasic residues of POMC than was previously found in cotransfection experiments. Other cellular regulatory mechanisms probably play a role in limiting the processing of POMC in vivo in the anterior pituitary, where gamma(3)MSH and alpha MSH are not found in significant amounts. C1 UNIV AUCKLAND, SCH BIOL SCI, AUCKLAND, NEW ZEALAND. RP FRIEDMAN, TC (reprint author), NICHHD, DEV NEUROBIOL LAB,CELLULAR NEUROBIOL SECT,BLDG 49, ROOM 5A-38, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. RI Birch, Nigel/H-2498-2011 OI Birch, Nigel/0000-0002-8417-3587 FU Wellcome Trust NR 49 TC 39 Z9 40 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1994 VL 135 IS 3 BP 854 EP 862 DI 10.1210/en.135.3.854 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PD460 UT WOS:A1994PD46000007 PM 8070378 ER PT J AU TOMIZUKA, T OEDA, T TAMURA, Y YOSHIDA, S STROTT, CA AF TOMIZUKA, T OEDA, T TAMURA, Y YOSHIDA, S STROTT, CA TI CHARACTERIZATION OF GUINEA-PIG ESTROGEN SULFOTRANSFERASE EXPRESSED BY CHINESE-HAMSTER OVARY CELL-K1 STABLE TRANSFECTANTS SO ENDOCRINOLOGY LA English DT Article ID ADENOSINE 3'-PHOSPHATE 5'-PHOSPHOSULFATE; PREGNENOLONE SULFOTRANSFERASE; MOLECULAR-CLONING; ADRENAL-CORTEX; PROTEINS; SULFATION; TISSUES AB Estrogen sulfotransferase (EST) activity expressed by Chinese hamster ovary (CHO)-K1 cells stably transfected with a plasmid containing a guinea pig EST complementary DNA insert was subjected to biochemical characterization, and the EST protein was further examined by nondenaturing isoelectric focusing and immunoblot analysis. CHO-K1 cells transfected with the same plasmid without the EST complementary DNA insert as well as untransfected CHO-K1 cells did not demonstrate either EST activity or the presence of an immunologically related protein. The EST expressed by the stably transfected CHO-K1 cells was found to manifest Michaelis Menten kinetics and would use only estrogenic steroids as substrates, whereas other forms of steroids, such as pregnenolone, dehydroepiandrosterone, cortisol, and testosterone, were not acted on. When 17 beta-estradiol was used as a substrate, sulfonation occurred exclusively at the 3 position; 17-sulfonate was not formed. Thus, the expressed EST acted selectively on the 3-hydroxyl group of phenolic steroids. The apparent K-m values for estrone, 17 beta-estradiol, and estriol were 60, 70, and 40 nM, respectively. The maximum velocity (V-max) determinations for estrone and 17 beta-estradiol were equivalent, whereas the V-max for estriol was reduced by 33%. Of the three estrogens, only 17 beta-estradiol caused substrate inhibition at a high concentration. Steroid sulfonation requires 3'-phosphoadenosine-5'phosphosulfate (PAPS) as the active sulfonate donor, and the K-m value for PAPS was 1.2 mu M. In steroid sulfotransferase reactions, two products are formed: the sulfonated steroid product and the desulfonated cofactor, 3'-phosphoadenosine-5'-phosphate (PAP). The sulfonation of 17 beta-estradiol was inhibited by PAP in a dose-dependent manner. In addition, the K-m for PAPS was increased by PAP, whereas the V-max was unaffected, indicating competitive inhibition (K-i, similar to 0.52 mu M). The EST protein expressed by the CHO-K1 cell transfectants demonstrated a mol wt of 34 kilodaltons, as determined by sodium dodecyl sulfate-gel electrophoresis. Additionally, when the expressed EST protein was subjected to isoelectric focusing, it was found to consist of multiple charge isoforms. These findings are comparable to what has been previously reported for native guinea pig adrenocortical EST. Furthermore, the charge isoform pattern that was demonstrated for the expressed EST was similar to the pattern observed for the native protein. C1 NICHHD, ENDOCRINOL & REPROD RES BRANCH, STEROID REGULAT SECT, BETHESDA, MD 20892 USA. CHIBA UNIV, SCH MED, DEPT INTERNAL MED 2, CHIBA 260, JAPAN. NR 35 TC 13 Z9 14 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 SEP PY 1994 VL 135 IS 3 BP 938 EP 943 DI 10.1210/en.135.3.938 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PD460 UT WOS:A1994PD46000018 PM 8070389 ER PT J AU HEINRICHS, C YANOVSKI, JA ROTH, AH YU, YM DOMENE, HM YANO, K CUTLER, GB BARON, J AF HEINRICHS, C YANOVSKI, JA ROTH, AH YU, YM DOMENE, HM YANO, K CUTLER, GB BARON, J TI DEXAMETHASONE INCREASES GROWTH-HORMONE RECEPTOR MESSENGER-RIBONUCLEIC-ACID LEVELS IN LIVER AND GROWTH-PLATE SO ENDOCRINOLOGY LA English DT Article ID LONGITUDINAL BONE-GROWTH; I IGF-I; BINDING-PROTEIN; GENE-EXPRESSION; RAT; COMPLEX AB Glucocorticoid inhibits linear growth and renders target tissues, particularly liver and growth plate, insensitive to GH. We hypothesized that glucocorticoid-induced GH insensitivity is due to decreased gene expression of the GH receptor at the messenger RNA (mRNA) level. To test this hypothesis, we treated 4.5-wk-old male rabbits (n = 6-9 per group) with ip dexamethasone or vehicle and measured GH receptor mRNA levels (by RNase protection assay) and serum GH-binding protein levels (by radioimmunoprecipitation assay). Contrary to our hypothesis, dexamethasone administered in growth-suppressing doses did not decrease GH receptor mRNA levels in liver or growth plate. Instead a tissue-specific stimulation of GH receptor mRNA levels was observed. The dose-response relationship of this effect was biphasic, since the lower growth-suppressing dose of dexamethasone (0.1 mg/kg.day) caused the greater increase in GH receptor mRNA levels, whereas the higher growth-suppressing dose (4 mg/kg.day) had less effect. The dexamethasone-induced increase in GH receptor mRNA was observed in growth plate and liver, target tissues important for linear growth, but not in kidney. Serum GH-binding protein levels also showed a stimulatory response to dexamethasone treatment, with a biphasic dose-response relationship. These data suggest that glucocorticoid-induced GH insensitivity cannot be explained by decreased GH receptor mRNA levels. To the contrary, dexamethasone causes a tissue-specific stimulation in GH receptor mRNA levels with a biphasic dose-response relationship. RP HEINRICHS, C (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N262, BETHESDA, MD 20892 USA. NR 23 TC 63 Z9 63 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1994 VL 135 IS 3 BP 1113 EP 1118 DI 10.1210/en.135.3.1113 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PD460 UT WOS:A1994PD46000042 PM 8070354 ER PT J AU MASON, DR ARORA, KK MERTZ, LM CATT, KJ AF MASON, DR ARORA, KK MERTZ, LM CATT, KJ TI HOMOLOGOUS DOWN-REGULATION OF GONADOTROPIN-RELEASING-HORMONE RECEPTOR-SITES AND MESSENGER-RIBONUCLEIC-ACID TRANSCRIPTS IN ALPHA-T3-1 CELLS SO ENDOCRINOLOGY LA English DT Article ID BETA-ADRENERGIC RECEPTORS; RAT ESTROUS-CYCLE; BETA-2-ADRENERGIC RECEPTOR; RNA LEVELS; MEDIATED ENDOCYTOSIS; PITUITARY; AGONIST; EXPRESSION; CLONING; GNRH AB GnRH is known to down-regulate its pituitary receptors by mechanisms that include endocytosis of the agonist-receptor complex. To evaluate the extent to which changes in receptor synthesis contribute to this process, the effects of GnRH and its analogs on GnRH receptor number and messenger RNA (mRNA) levels were analyzed in the alpha T3-1 gonadotroph cell line. Treatment with GnRH or its potent agonist analog, des-Gly(10)-[D-Ala(6)]GnRH N-ethylamide, reduced GnRH receptor number in a time- and dose-dependent manner, with a half-maximal decrease in response to 10(-6) M GnRH or agonist analog by 75 min. The maximum decrease in receptor number (to 31% of the control value) was sustained for up to 72 h. In alpha T3-1 cells incubated with 10(-8) M GnRH or agonist analog, the GnRH receptors fell by 28% and 46% after 2 h, respectively; no change in receptors occurred after treatment with 10(-8) M GnRH antagonist ([D-pGlu(1),D-Phe(2),D-Trp(3,6)]GnRH). Time- and dose-dependent reductions in the level of receptor mRNA were also observed after treatment of alpha T3-1 cells with GnRH and the agonist analog. However, the maximal reduction in mRNA levels (to 60-70% of the control value) was consistently less than the decline in receptor number. These results indicate that the mechanism of GnRH receptor down-regulation in alpha T3-1 gonadotrophs includes reduction of receptor synthesis secondary to decreases in receptor mRNA levels. The finding that reductions in mRNA levels were relatively less than the decreases in receptor number is consistent with the involvement of additional mechanisms, including endocytosis and degradation, in down-regulation of the GnRH receptor. C1 NICHHD, ENDOCRINOL & REPROD RES BRANCH, BETHESDA, MD 20892 USA. UNIV CANTERBURY, DEPT ZOOL, CHRISTCHURCH 1, NEW ZEALAND. NR 41 TC 59 Z9 59 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 SEP PY 1994 VL 135 IS 3 BP 1165 EP 1170 DI 10.1210/en.135.3.1165 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PD460 UT WOS:A1994PD46000048 PM 8070359 ER PT J AU TSIGOS, C CHROUSOS, GP AF TSIGOS, C CHROUSOS, GP TI PHYSIOLOGY OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS IN HEALTH AND DYSREGULATION IN PSYCHIATRIC AND AUTOIMMUNE DISORDERS SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Review ID CORTICOTROPIN-RELEASING-FACTOR; CENTRAL NERVOUS-SYSTEM; HORMONE-SECRETION INVITRO; FAMILIAL GLUCOCORTICOID RESISTANCE; POTENTIAL CLINICAL IMPLICATIONS; HYPOPHYSIAL-PORTAL CIRCULATION; INSULIN-INDUCED HYPOGLYCEMIA; STRESS-INDUCED INHIBITION; SUSCEPTIBLE LEWIS RATS; ADRENOCORTICOTROPIN SECRETION AB The hypothalamic-pituitary-adrenal (HPA) axis is the endocrine limb of the ''stress system'' that, together with the sympathetic nervous system, plays a crucial role in maintaining homeostasis. This article briefly reviews current knowledge on the physiology of the HPA axis, including the regulation of its principle modulators, CRH and arginine vasopressin, its interactions with the immune system and other endocrine axes, and its altered regulation or dysregulation in various physiologic and pathophysiologic states, respectively. C1 NIH,PEDIAT ENDOCRINOL SECT,DEV ENDOCRINOL BRANCH,BETHESDA,MD. NIH,PEDIAT ENDOCRINOL TRAINING PROGRAM,BETHESDA,MD. RP TSIGOS, C (reprint author), NIH,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N262,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 157 TC 97 Z9 103 U1 1 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD SEP PY 1994 VL 23 IS 3 BP 451 EP 466 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PH546 UT WOS:A1994PH54600002 PM 7805648 ER PT J AU YANOVSKI, JA CUTLER, GB AF YANOVSKI, JA CUTLER, GB TI GLUCOCORTICOID ACTION AND THE CLINICAL-FEATURES OF CUSHINGS-SYNDROME SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Review ID SPINAL EPIDURAL LIPOMATOSIS; GASTRIC-INHIBITORY POLYPEPTIDE; STEROID-HORMONE RECEPTORS; URINARY FREE CORTISOL; ADRENOCORTICOTROPIC HORMONE; INDUCED OSTEOPOROSIS; FAT DISTRIBUTION; SKELETAL-MUSCLE; RENAL-FAILURE; DNA-BINDING AB This article reviews the mechanism of action of glucocorticoids at the cellular level. The effects of excessive concentrations of glucocorticoids on body tissues are described, along with discussion of the pathophysiology underlying these effects. The signs, symptoms, and laboratory findings of Cushing's syndrome are highlighted. RP YANOVSKI, JA (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,DEV ENDOCRINOL SECT,BLDG 10,ROOM 10N262,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 151 TC 85 Z9 87 U1 0 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD SEP PY 1994 VL 23 IS 3 BP 487 EP 509 PG 23 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PH546 UT WOS:A1994PH54600004 PM 7805650 ER PT J AU FINDLING, JW DOPPMAN, JL AF FINDLING, JW DOPPMAN, JL TI BIOCHEMICAL AND RADIOLOGIC-DIAGNOSIS OF CUSHINGS-SYNDROME SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; NODULAR ADRENOCORTICAL DISEASE; DEXAMETHASONE SUPPRESSION TEST; ECTOPIC ACTH SYNDROME; BRONCHIAL CARCINOID-TUMORS; PITUITARY-ADRENAL-FUNCTION; URINARY FREE CORTISOL; CHRONIC-RENAL-FAILURE; DIFFERENTIAL-DIAGNOSIS; STIMULATION TEST AB Technologic advances during the past decade have greatly improved the biochemical and radiologic diagnosis of Cushing's syndrome. This article describes how the introduction of a specific and sensitive immunoradiometric assay for ACTH, CRH stimulation testing, inferior petrosal sinus sampling for ACTH, computed tomography, and MR imaging of the pituitary and adrenal glands have provided the necessary tools for an accurate diagnosis and differential diagnosis of Cushing's syndrome. C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT RADIOL,BETHESDA,MD. RP FINDLING, JW (reprint author), ST LUKES HOSP,CTR ENDOCRINE DIABET,2901 W KINNICKINNIC RIVER PKWY,SUITE 503,MILWAUKEE,WI 53215, USA. NR 80 TC 72 Z9 77 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD SEP PY 1994 VL 23 IS 3 BP 511 EP 537 PG 27 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PH546 UT WOS:A1994PH54600005 PM 7805651 ER PT J AU WINK, DA WINK, CB NIMS, RW FORD, PC AF WINK, DA WINK, CB NIMS, RW FORD, PC TI OXIDIZING INTERMEDIATES GENERATED IN THE FENTON REAGENT - KINETIC ARGUMENTS AGAINST THE INTERMEDIACY OF THE HYDROXYL RADICAL SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT 2nd International Meeting on Molecular Mechanics of Metal Toxicity and Carcinogenicity CY JAN 10-17, 1993 CL MADONNA CAMPIGLIO, ITALY DE FENTON REAGENT; HYDROXYL RADICAL; METALLO-OXO ID HYDROGEN-PEROXIDE; N-NITROSODIMETHYLAMINE; AQUEOUS-SOLUTION; IRON; DEGRADATION; TOXICITY; ACID AB It has long been recognized that the aqueous mixture of hydrogen peroxide and ferrous ion, known as the Fenton reagent, generates powerful oxidants. Furthermore, the chemical intermediates and reaction pathways of the type generated by this reagent have been implicated in oxidative damage in biological systems. Although the subject continues to be debated, the hydroxyl radical (OH) is generally invoked as the predominant oxidizing intermediate formed by the Fenton reagent. However, recent results from this laboratory have demonstrated that the principal pathway for the Fenton-media ted oxidation of N-nitrosodimethylamine does not involve OH, but instead must invoke the intermediacy of another strongly oxidizing species. This conclusion was based on stopped-flow spectrophotometric observation of a transient, A, believed to be an iron(II) nitrosyl adduct, which was formed at a rate fivefold faster than that predicted for formation of OH. Subsequent experiments have shown that methanol and other organic compounds can quench the formation of A. This quenching procedure provides a unique spectrophotometric probe with which to examine the relative reactivities of putative Fenton-type oxidizing intermediates toward organic substrates. Presented here are the results of several such quenching studies, plus an overview of our mechanistic investigations of the Fenton reaction. C1 UNIV CALIF SANTA BARBARA,DEPT CHEM,SANTA BARBARA,CA 93106. RP WINK, DA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,CHEM SECT,COMPARAT CARCINOGENESIS LAB,BLDG 538,ROOM 205E,FREDERICK,MD 21702, USA. RI Ford, Peter/D-1826-2011 OI Ford, Peter/0000-0002-5509-9912 NR 25 TC 37 Z9 37 U1 1 U2 7 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 1994 VL 102 SU 3 BP 11 EP 15 DI 10.2307/3431754 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA PK085 UT WOS:A1994PK08500003 PM 7843082 ER PT J AU SHI, XL DALAL, N KASPRZAK, KS AF SHI, XL DALAL, N KASPRZAK, KS TI ENHANCED GENERATION OF HYDROXYL RADICAL AND SULFUR-TRIOXIDE ANION-RADICAL FROM OXIDATION OF SODIUM-SULFITE, NICKEL(II) SULFITE, AND NICKEL SUBSULFIDE IN THE PRESENCE OF NICKEL(II) COMPLEXES SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT 2nd International Meeting on Molecular Mechanics of Metal Toxicity and Carcinogenicity CY JAN 10-17, 1993 CL MADONNA CAMPIGLIO, ITALY DE HYDROXYL RADICAL; SULFUR TRIOXIDE ANION RADICAL; SULFITE; NICKEL(II) SULFITE; NICKEL SUBSULFIDE; NICKEL(II) COMPLEXES ID SPIN TRAPPING EVIDENCE; OXYGEN; CARCINOGENICITY; AUTOXIDATION; DAMAGE; ACID AB Electron spin resonance (ESR) spin trapping was utilized to investigate the generation of free radicals from oxidation of sodium sulfite, nickel(II) subsulfite, and nickel subsulfide (Ni3S2) by ambient oxygen or H2O2 at pH 7.4. The spin trap used was 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Under ambient oxygen, a solution of sodium sulfite alone generated predominantly sulfur trioxide anion radical (.SO3-) due to the autoxidation of sulfite: Addition of nickel(II) chloride [Ni(II)] enhanced the .SO3- yield about 4-fold. Incubation of sulfite with Ni(II) in the presence of chelators such as tetraglycine, histidine, beta-alanyl-3-methyl-L-histidine (anserine), beta-alanyl-L-histidine (camosine), gamma-aminobutyryl-L-histidine (homocarnosine); glutathione, and penicillamine did not have any significant effect on that enhancement. in contrast, albumin, and especially glycylglycylhistidine (GlyGlyHis), augmented the enhancing effect of Ni(II) by factors of 1.4 acid 4, respectively. Computer simulation analysis of the spin-adduct spectrum and formate scavenging experiment showed that the mixture of sodium sulfite, Ni(II), and GlyGlyHis generated both hydroxyl (.OH) radical and .SO3--radical, in the ratio of approximately 1:2. The free-radical spin adduct intensity reached its saturation level in about 5 min. The yield of the radical adducts could be slightly reduced by deferoxamine and very strongly reduced by diethylenetriaminepentaacetic acid (DTPA). Aqueous suspensions of sparingly soluble nickel(II) sulfite in the presence of air and GlyGlyHis generated surface-located .SO3- and OH radicals. The same radicals were generated in Ni3S2 suspension in the presence of GlyGlyHis and H2O2, indicating sulfite production by oxidation of the sulfide moiety of this compound. In view of the present results, the exceptionally high carcinogenic potential of Ni3S2 appears to be due to the ability of both the nickel and sulfide constituents of the molecule to facilitate the generation of genotoxic radicals. C1 W VIRGINIA UNIV,DEPT CHEM,MORGANTOWN,WV 26506. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RI Shi, Xianglin/B-8588-2012 NR 44 TC 28 Z9 28 U1 0 U2 11 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 1994 VL 102 SU 3 BP 91 EP 96 DI 10.2307/3431768 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA PK085 UT WOS:A1994PK08500017 PM 7843142 ER PT J AU COOGAN, TP SHIRAISHI, N WAALKES, MP AF COOGAN, TP SHIRAISHI, N WAALKES, MP TI APPARENT QUIESCENCE OF THE METALLOTHIONEIN GENE IN THE RAT VENTRAL PROSTATE - ASSOCIATION WITH CADMIUM-INDUCED PROSTATE TUMORS IN RATS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT 2nd International Meeting on Molecular Mechanics of Metal Toxicity and Carcinogenicity CY JAN 10-17, 1993 CL MADONNA CAMPIGLIO, ITALY DE CADMIUM; PROSTATE; METALLOTHIONEIN; CARCINOGENESIS; TUMORS; RAT; RNA ID WISTAR CRL-(WI)BR RATS; DOSE-RESPONSE ANALYSIS; INJECTION SITE; ZINC; CARCINOGENICITY; INDUCTION; TESTES AB Several chronic studies in rats indicating that cadmium exposure can induce tumors of the ventral prostate have recently been completed in our laboratory. in one such study, a single dose of cadmium, s.c., increased prostatic tumor incidence only at doses below 5.0 mu mol/kg, the approximate threshold for cadmium-induced testicular damage. In a further study, prostatic tumors were elevated with higher doses of cadmium (30 mu mol/kg, s.c.) if testicular damage was prevented by zinc pretreatment. Most recently, we found that dietary cadmium (25 to 200 mu g/g) also can increase prostatic neoplastic lesions, but these were reduced by zinc-deficient diets. Thus it appears that cadmium produces prostatic tumors only if testicular function is maintained. Furthermore, we find that metallothionein (MT), a protein associated with cadmium tolerance, may be deficient in the rat prostate, and the prostatic MT gene, at least in the ventral lobe, is unresponsive to metal stimuli. In liver, MT gene expression, as assessed by MT-I mRNA, was quite apparent in control tissue and was induced in a dose-dependent manner 24 hr following cadmium exposure (1 to 10 mu mol/kg, s.c.). However, in the ventral prostate very low constitutive levels of MT-I mRNA were detected and increases did not occur with cadmium exposure. Cadmium concentrations in the Ventral prostate were in excess of those that cause significant induction in the liver. in sharp contrast to the gene in the Ventral prostate, in the dorsal prostate the MT gene was quite active. The dorsal prostate is not susceptible to cadmium carcinogenesis. The association between tissue-specific quiescence of the MT gene and susceptibility to cadmium carcinogenesis deserves further study. C1 NCI,FREDERICK CANC RES & DEV CTR,INORGAN CARCINOGENESIS SECT,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NR 13 TC 19 Z9 19 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 1994 VL 102 SU 3 BP 137 EP 139 DI 10.2307/3431777 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA PK085 UT WOS:A1994PK08500026 PM 7843088 ER PT J AU SHIRAISHI, N BARTER, RA UNO, H WAALKES, MP AF SHIRAISHI, N BARTER, RA UNO, H WAALKES, MP TI EFFECT OF PROGESTERONE PRETREATMENT ON CADMIUM TOXICITY IN MALE FISCHER (F344/NCR) AND WISTAR (WF/NCR) RATS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT 2nd International Meeting on Molecular Mechanics of Metal Toxicity and Carcinogenicity CY JAN 10-17, 1993 CL MADONNA CAMPIGLIO, ITALY DE CADMIUM TOXICITY; PROGESTERONE; HEPATOTOXICITY; METALLOTHIONEIN; TESTICULAR CADMIUM-BINDING PROTEIN ID BINDING PROTEINS; METALLOTHIONEIN AB A previous report indicated that progesterone pretreatment can markedly reduce cadmium (Cd) toxicity in male NAW mice. Therefore we examined the effects of progesterone pretreatment on Cd toxicity in male Fischer (F344) and Wistar (WF) rats. A single subcutaneous injection of 10 or 30 mu mole (CdCl2)/kg proved nonlethal over 24 hr but caused the typical spectrum of testicular lesions in these rats. Moreover, when F344 rats were pretreated with progesterone (100 mg/kg, sc, at -48, -24, and 0 hr) and then given cadmium (20 mu mole CdCl2/kg, 0 hr), this dose of cadmium proved very toxic, unexpectedly causing 53% mortality. Progesterone pretreatment had no effect on cadmium-induced lethality in WF rats or on testicular lesions in either strain. Significant elevations in serum lactate dehydrogenase (LDH) activity, indicative of hepatotoxicity, were also observed in progesterone-pretreated F344 rats given cadmium as compared to rats given Cd alone. Progesterone did not induce increases in hepatic or renal metallothionein (MT) and hepatic or testicular MT-I mRNA levels in F344 rats. In contrast, levels of the testicular cadmium-binding protein (TCBP) in progesterone-pretreated F344 rats were doubled. This increase in TCBP provided no protection against cadmium toxicity in the testes. These results indicate that, in contrast to previously reported data for mice, progesterone pretreatment increased the lethality of cadmium in male F344 rats and had no effect on cadmium-induced testicular toxicity in F344 and WF rats. C1 NCI,FREDERICK CANC RES & DEV CTR,INORGAN CARCINOGENESIS SECT,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NR 16 TC 4 Z9 4 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 1994 VL 102 SU 3 BP 277 EP 280 DI 10.2307/3431801 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA PK085 UT WOS:A1994PK08500050 PM 7843114 ER PT J AU FISHER, BE AF FISHER, BE TI DOWNSTREAM IN AMERICA SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material RP FISHER, BE (reprint author), NIEHS,ENVIRONM TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709, USA. NR 3 TC 2 Z9 2 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 1994 VL 102 IS 9 BP 740 EP 745 DI 10.2307/3432132 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA PG569 UT WOS:A1994PG56900008 PM 9657703 ER PT J AU BERGERON, JM CREWS, D MCLACHLAN, JA AF BERGERON, JM CREWS, D MCLACHLAN, JA TI PCBS AS ENVIRONMENTAL ESTROGENS - TURTLE SEX DETERMINATION AS A BIOMARKER OF ENVIRONMENTAL CONTAMINATION SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID POLYCHLORINATED-BIPHENYLS; TEMPERATURE; ESTRADIOL; REVERSAL AB Polychlorinated biphenyls (PCBs) are wide-spread, low-level environmental pollutants associated with adverse heath effects such as immune suppression and teratogenicity. There is increasing evidence that some PCB compounds are capable of disrupting reproductive and endocrine function in fish, birds, and mammals, including humans, particularly during development. Research on the mechanism through which these compounds act to alter reproductive function indicates estrogenic activity, whereby the compounds may be altering sexual differentiation. Here we demonstrate the estrogenic effect of some PCBs by reversing gonadal sex in a reptile species that exhibits temperature-dependent sex determination. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP BERGERON, JM (reprint author), UNIV TEXAS,INST REPROD BIOL,DEPT ZOOL,AUSTIN,TX 78712, USA. FU PHS HHS [00135] NR 17 TC 262 Z9 270 U1 6 U2 42 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 1994 VL 102 IS 9 BP 780 EP 781 DI 10.2307/3432139 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA PG569 UT WOS:A1994PG56900015 PM 9657710 ER PT J AU WEINBERG, CR MOLEDOR, E BAIRD, DD AF WEINBERG, CR MOLEDOR, E BAIRD, DD TI IS THERE A SEASONAL PATTERN IN RISK OF EARLY-PREGNANCY LOSS SO EPIDEMIOLOGY LA English DT Article DE SPONTANEOUS ABORTION; SEASONALITY; FERTILITY AB We recruited 221 women with no known fertility problems who were discontinuing contraception to conceive a pregnancy. The primary objective of this prospective study was to estimate the incidence of very early pregnancy loss by using a highly sensitive and specific assay to detect the pregnancy hormone chorionic gonadotropin in first morning urine specimens. We found the risk of early pregnancy loss, defined as loss within 6 weeks of the last menstrual period, to vary by season of conception, with a large amplitude and some consistency across the 3 years of the study. Such a seasonal pattern may reflect the contribution of an environ mental factor that varies with season. The peaks in risk ranged from early September to early December. A seasonal pattern of early pregnancy loss should contribute to a corresponding lagged seasonal pattern in livebirths. Accordingly, we looked for corroborative evidence in regional birth data from the same years. There was some correspondence, but this was largely limited to the first: year of the study. RP WEINBERG, CR (reprint author), NIEHS,STAT & BIOMATH BRANCH,MD A3-03,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Wilcox, Allen/0000-0002-3376-1311; Baird, Donna/0000-0002-5544-2653 NR 0 TC 27 Z9 27 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 1994 VL 5 IS 5 BP 484 EP 489 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PD244 UT WOS:A1994PD24400003 PM 7986861 ER PT J AU WEINBERG, CR AF WEINBERG, CR TI THE INFLUENCE OF OCCUPATIONAL ACTIVITY ON THE MENSTRUAL-CYCLE AND FECUNDABILITY (VOL 5, PG 476, 1994) SO EPIDEMIOLOGY LA English DT Correction, Addition RP WEINBERG, CR (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 1994 VL 5 IS 5 BP 563 EP 564 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PD244 UT WOS:A1994PD24400021 PM 7986876 ER PT J AU BUTINI, L DEFOUGEROLLES, AR VACCAREZZA, M GRAZIOSI, C COHEN, DI MONTRONI, M SPRINGER, TA PANTALEO, G FAUCI, AS AF BUTINI, L DEFOUGEROLLES, AR VACCAREZZA, M GRAZIOSI, C COHEN, DI MONTRONI, M SPRINGER, TA PANTALEO, G FAUCI, AS TI INTERCELLULAR-ADHESION MOLECULES (ICAM)-1 ICAM-2 AND ICAM-3 FUNCTION AS COUNTER-RECEPTORS FOR LYMPHOCYTE FUNCTION-ASSOCIATED MOLECULE-1 IN HUMAN IMMUNODEFICIENCY VIRUS-MEDIATED SYNCYTIA FORMATION SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE ADHESION MOLECULES; SYNCYTIA; HUMAN IMMUNODEFICIENCY VIRUS ID FUNCTION-ASSOCIATED ANTIGEN-1; ENVELOPE GLYCOPROTEIN; HIV-INFECTION; AIDS RETROVIRUS; MEMBRANE-FUSION; IMMUNE-SYSTEM; HTLV-III/LAV; T4 MOLECULE; SOLUBLE CD4; LFA-1 AB It has been previously demonstrated that lymphocyte function-associated molecule 1 (LFA-1) plays a major role in human immunodeficiency virus (HIV)-mediated syncytia formation. In the present study we investigated the involvement of intercellular adhesion molecule-1 (ICAM-1), ICAM-2 and ICAM-3 in the process. The ability of monoclonal antibodies (mAb) directed against ICAM-1, ICAM-2 and ICAM-3 to block syncytia was analyzed either in phytohemagglutinin (PHA)-activated lymphocytes infected in vitro with primary or laboratory strains of HIV or by coculturing a T cell line stably expressing HIV envelope with PHA-activated lymphocytes. Complete inhibition of syncytia formation was observed only by the simultaneous addition to the cell cultures of all (i.e. anti-ICAM-1, anti-ICAM-2 and anti-ICAM-3) mAb. These results indicate that the interaction between LFA-1 and ICAM is a critical step in HIV-mediated syncytia formation, and that ICAM-1, ICAM-2 and ICAM-3 are the receptor molecules for the LFA-1-dependent syncytia formation. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. UNIV ANCONA,INST INTERNAL MED,DEPT CLIN IMMUNOL,ANCONA,ITALY. HARVARD UNIV,SCH MED,DEPT PATHOL,COMM IMMUNOL,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA. RI Pantaleo, Giuseppe/K-6163-2016; OI VACCAREZZA, Mauro/0000-0003-3060-318X NR 41 TC 42 Z9 43 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD SEP PY 1994 VL 24 IS 9 BP 2191 EP 2195 DI 10.1002/eji.1830240939 PG 5 WC Immunology SC Immunology GA PJ300 UT WOS:A1994PJ30000038 PM 7916296 ER PT J AU POGGI, A DEMAREST, JF COSTA, P BIASSONI, R PELLA, N PANTALEO, G MINGARI, MC MORETTA, L AF POGGI, A DEMAREST, JF COSTA, P BIASSONI, R PELLA, N PANTALEO, G MINGARI, MC MORETTA, L TI EXPRESSION OF A WIDE T-CELL RECEPTOR V-BETA REPERTOIRE IN HUMAN T-LYMPHOCYTES DERIVED IN-VITRO FROM EMBRYONIC LIVER-CELL PRECURSORS SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Note DE DIFFERENTIATION; T LYMPHOCYTES; EMBRYONIC PRECURSORS; B-BETA REPERTOIRE; CD3/TCR ID NATURAL-KILLER-CELLS; EXTRATHYMIC DIFFERENTIATION AB As shown recently, CD3(+)/TcR(+) functional T lymphocytes can be derived in culture from embryonic liver cell precursors at a gestational age (6-8 weeks) preceeding the colonization of the epithelial thymus. In this report, we analyzed the V beta repertoire of T lymphocytes derived from embryonic liver by applying a quantitative reverse transcriptase-polymerase chain reaction technique. To this end, oligonucleotide primers for C alpha or the various human V beta have been used to study both freshly derived embryonic liver cell suspensions and CD3(+)/TcR(+) populations derived after approximately 6 weeks upon stimulation with 1% phytohemagglutinin and culture in 100 units/ml recombinant interleukin-2. In order to exclude possible contaminations with mother-derived T lymphocytes, only T cells displaying both X and Y chromosomal sequences (i.e. derived from male embryos) were further analyzed. While neither C alpha nor the various V beta could be detected in fresh liver cells, C alpha and the large majority of V beta were detected in in vitro cultured populations. The levels of the various V beta expressed by embryo-derived T cells was similar to that detected in adult peripheral blood-derived T lymphocytes. These experiments indicate that the immature liver precursors can potentially give rise in vitro to T cells which express a wide V beta repertoire and may provide a suitable in vitro system for the analysis of the selection processes mediated by either major histocompatibility complex antigen or superantigens. C1 NIH,BETHESDA,MD 20892. NIID,BETHESDA,MD. UNIV GENOA,IST ONCOL CLIN & SPERIMENTALE,I-16126 GENOA,ITALY. UNIV TURIN,DIPARTIMENTO MED & ONCOL SPERIMENTALE,NOVARA,ITALY. RP POGGI, A (reprint author), IST NAZL RIC CANC,IMMUNOPATHOL LAB,VIALE BENEDETTO XV N10,I-16132 GENOA,ITALY. RI Pantaleo, Giuseppe/K-6163-2016; OI Poggi, Alessandro/0000-0002-1860-430X NR 10 TC 6 Z9 6 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD SEP PY 1994 VL 24 IS 9 BP 2258 EP 2261 DI 10.1002/eji.1830240949 PG 4 WC Immunology SC Immunology GA PJ300 UT WOS:A1994PJ30000048 PM 8088340 ER PT J AU EACOTT, MJ GAFFAN, D MURRAY, EA AF EACOTT, MJ GAFFAN, D MURRAY, EA TI PRESERVED RECOGNITION MEMORY FOR SMALL SETS, AND IMPAIRED STIMULUS IDENTIFICATION FOR LARGE SETS, FOLLOWING RHINAL CORTEX ABLATIONS IN MONKEYS SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE VISUAL MEMORY; DISCRIMINATION LEARNING; CYNOMOLGUS; MATCHING-TO-SAMPLE ID LONG-TERM-MEMORY; FORNIX TRANSECTION; INFEROTEMPORAL CORTEX; HIPPOCAMPAL-FORMATION; TEMPORAL CORTEX; LESIONS; PRIMATE; ORGANIZATION; ANTERIOR; NEURONS AB Seven cynomolgus monkeys (Macaca fascicularis) performed a series of tasks designed to assess their visual memory and their ability to identify visual stimuli. Preoperatively they were trained and tested in delayed and simultaneous matching-to-sample, both with a large stimulus set and with a small stimulus set; there were similar to 500 million possible stimuli in the large set, which effectively means that stimuli were trial-unique with this set, while in the small set there were only four stimuli, which appeared repeatedly in every session of training with the small set. Three of the monkeys then had the cortex within and adjacent to the rhinal sulcus removed bilaterally while the other four served as an unoperated control group. Postoperatively, the animals with ablation of the rhinal cortex showed severe impairment in delayed matching-to-sample with the large set. With the large set they were also impaired, however, in matching-to-sample with no delay between sample and test (0 s delay) and in simultaneous matching-to-sample, in which the sample and the two choice patterns were simultaneously present for inspection. The impairment in simultaneous matching-to-sample was particularly clear when the task was made more difficult by reducing the physical discriminability of the trial-unique stimuli. With the small set of four stimuli, the animals with rhinal cortex ablation were not significantly impaired in overall performance level in delayed matching-to-sample, though their level was on average below that of the normal control animals, The stimulus set was then further restricted, so that there were now only two stimuli used throughout; in this condition, the animals with rhinal cortex ablation performed delayed matching-to-sample without any suggestion of impairment, showing indistinguishable performance levels from those of the control animals over a range of forgetting intervals. Subsequently, the animals were trained in trial-unique non-matching-to-sample with 0 s delay, which required reversal of the matching-to-sample rule they had previously learned; animals with rhinal cortex ablation showed a clear impairment in this rule-reversal learning. The final experimental task was a concurrent discrimination learning task in which 20 pairs of stimuli were presented once per session; the animals with rhinal cortex ablation learned more slowly than the control animals on average, but the difference between the groups did not attain statistical significance. Overall, this pattern of deficits and of preserved abilities is clearly inconsistent with the idea that rhinal cortex ablation produces an impairment in all forms of visual recognition memory, and only in visual recognition memory. Instead, the present results indicate a general impairment in the capacity for knowledge about visual stimuli. C1 UNIV OXFORD,DEPT EXPTL PSYCHOL,OXFORD OX1 3UD,ENGLAND. NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. RI Eacott, madeline /D-6194-2013; OI Eacott, madeline /0000-0002-1694-2137; Murray, Elisabeth/0000-0003-1450-1642 NR 33 TC 223 Z9 224 U1 1 U2 14 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD SEP 1 PY 1994 VL 6 IS 9 BP 1466 EP 1478 DI 10.1111/j.1460-9568.1994.tb01008.x PG 13 WC Neurosciences SC Neurosciences & Neurology GA PF809 UT WOS:A1994PF80900008 PM 8000570 ER PT J AU GRAHAM, CH CONNELLY, I MACDOUGALL, JR KERBEL, RS STETLERSTEVENSON, WG LALA, PK AF GRAHAM, CH CONNELLY, I MACDOUGALL, JR KERBEL, RS STETLERSTEVENSON, WG LALA, PK TI RESISTANCE OF MALIGNANT TROPHOBLAST CELLS TO BOTH THE ANTIPROLIFERATIVE AND ANTI-INVASIVE EFFECTS OF TRANSFORMING GROWTH-FACTOR-BETA SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID EXTRACELLULAR-MATRIX COMPONENTS; IV COLLAGENASE; DIFFERENTIAL SENSITIVITY; CARCINOMA-CELLS; EXPRESSION; INVITRO; CYTOTROPHOBLAST; LINES; FACTOR-BETA-1; TGF-BETA-1 AB Human placental trophoblast invasion of the uterus is a highly controlled event. We had shown that transforming growth factor-beta (TGF-beta) produced in the pregnant uterus controls invasiveness and reduces proliferation of first trimester placental trophoblasts in vitro. The anti-invasive effect of TGF-beta was due, at least in part, to induction of tissue inhibitor of metalloproteinases (TIMP)-1. In the present study we compared the effects of TGF-beta on proliferation ([H-3]-TdR incorporation) and invasiveness (3-day Matrigel invasion assay) of JAR and JEG-3 choriocarcinoma cells vs normal first trimester human trophoblast cells. Transcripts of type IV collagenases (72- and 92-kDa enzymes, i.e., gelatinases A and B) and their inhibitors (TIMP-1 and TIMP-2) in these cells were measured by Northern analysis, and secretion of gelatinases and plasminogen activators (PAs) was evaluated by gel zymography. The results revealed that: (a) TGF-beta inhibited invasiveness and proliferation of normal trophoblast but not JAR and JEG-3 choriocarcinoma cells; (b) gelatinase A mRNA, expressed by the normal trophoblast and JAR cells, was upregulated in the presence of TGF-beta; (c) gelatinase B mRNA was not detected in the total RNA preparations of treated or untreated normal trophoblast or choriocarcinoma cells; (d) TGF-beta significantly upregulated the levels of TIMP-1 mRNA in the normal trophoblasts, but this transcript was very low in treated as well as untreated choriocarcinoma cells; TGF-beta also upregulated the 3.5-kb TIMP-2 message in the normal trophoblast; (e) gelatin zymography revealed a distinct band of approximately 68-kDa (gelatinase A) in the conditioned media of normal trophoblast and JAR cells; however, TGF-beta did not change the level of secretion of this gelatinase; and (f) the normal trophoblast also exhibited significant PA secretion (casein zymography) which was reduced in the presence of TGF-beta. PA secretion by the malignant trophoblast cells was low and unaffected by TGF-beta. These findings suggest that choriocarcinoma cells may become refractory to the mechanisms which control normal trophoblast proliferation and invasiveness. Concurrent resistance to antiproliferative and anti-invasive molecules such as TGF-beta may be highly relevant to tumor progression. (C) 1994 Academic Press, Inc. C1 UNIV WESTERN ONTARIO, DEPT ANAT, LONDON N6A 5C1, ON, CANADA. SUNNYBROOK HLTH SCI CTR, DIV CANC RES, TORONTO M4N 3M5, ON, CANADA. NCI, PATHOL LAB, BETHESDA, MD 20892 USA. RP GRAHAM, CH (reprint author), QUEENS UNIV, DEPT ANAT & CELL BIOL, KINGSTON K7L 3N6, ON, CANADA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 35 TC 124 Z9 129 U1 0 U2 1 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 SEP PY 1994 VL 214 IS 1 BP 93 EP 99 DI 10.1006/excr.1994.1237 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA PF634 UT WOS:A1994PF63400011 PM 8082752 ER PT J AU AKIYAMA, T WHITAKER, B FEDERSPIEL, M HUGHES, SH YAMAMOTO, H TAKEUCHI, T BRUMBAUGH, J AF AKIYAMA, T WHITAKER, B FEDERSPIEL, M HUGHES, SH YAMAMOTO, H TAKEUCHI, T BRUMBAUGH, J TI TISSUE-SPECIFIC EXPRESSION OF MOUSE TYROSINASE GENE IN CULTURED CHICKEN-CELLS SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID RETROVIRAL VECTORS; TRANSGENIC MICE; PROMOTER; MELANOCYTES; LOCUS; CDNA AB A mouse tyrosinase cDNA has been combined with different promoters and inserted into several replication-competent avian leukosis proviruses and the viruses were transferred into cultured albino chick cells by viral infection. Expression of the tyrosinase gene depended on one of four promoter sequences: the resident constitutive promoter (Rous sarcoma virus long-terminal repeat; RSV-LTR), 471 bp from the mouse tyrosinase gene-associated promoter, 519 bp from the Japanese quail tyrosinase gene associated promoter, or 369 bp from the quail tyrosinase promoter. The infected cells expressed tyrosinase and produced pigment which could be seen with the light microscope. Immunofluorescence microscopy, using an anti mouse tyrosinase T1-specific antibody, also showed the presence of mouse tyrosinase. When infected with the same viral titer, gene expression was highest with the constitutive LTR promoter. The quail tyrosinase promoter, while less efficient than the LTR, was more efficient than the other tyrosinase promoter. Fibroblasts and hepatocytes infected with the construct carrying the constitutive promoter or the truncated quail promoter expressed tyrosinase. The mouse and quail promoters appeared to show tissue-specific expression since fibroblasts and hepatocytes infected with viruses carrying these promoters did not express mouse tyrosinase. Toxicity is associated with constitutive expression of tyrosinase in nonmelanocytes. Therefore the viruses that carry the tissue specific promoters should be useful for in vivo studies. (C) 1994 Academic Press, Inc. C1 UNIV NEBRASKA,LINCOLN,NE 68588. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. TOHOKU UNIV,INST BIOL,SENDAI,MIYAGI 980,JAPAN. RP AKIYAMA, T (reprint author), KEIO UNIV,DEPT BIOL,KOHOKU KU,HIYASHI 4-1-1,YOKOHAMA,KANAGAWA 223,JAPAN. FU NCI NIH HHS [N01-CO-74101] NR 26 TC 10 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD SEP PY 1994 VL 214 IS 1 BP 154 EP 162 DI 10.1006/excr.1994.1244 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA PF634 UT WOS:A1994PF63400018 PM 8082718 ER PT J AU GALANTI, N DVORAK, JA GRENET, J MCDANIEL, JP AF GALANTI, N DVORAK, JA GRENET, J MCDANIEL, JP TI HYDROXYUREA-INDUCED SYNCHRONY OF DNA-REPLICATION IN THE KINETOPLASTIDA SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID FLOW CYTOMETRIC ANALYSIS; TRYPANOSOMA-CRUZI; CELL-CYCLE; IDENTIFICATION; SEQUENCE AB We have developed a reliable and reproducible method to induce synchrony of the DNA synthetic cycle in the Kinetoplastida. The method involves treatment of cultures with 20 mM hydroxyurea (HU) and fetal bovine serum. Both stationary-phase and exponential-phase cultures can be synchronized. However, in the case of exponential-phase cultures the population doubling time and rate of DNA synthesis of the population influenced the time of exposure to HU. The treatment of kinetoplastids with 20 mM HU did not adversely affect the cells as judged by oxygen consumption, RNA, and protein content. We postulate that the requirement for high HU levels, which would be toxic to vertebrate cells, may be due to a lower affinity of kinetoplastid ribonucleotide reductase, the target enzyme for HU. Some of the kinetoplastids are pathogens of man and his food chain. Consequently, the development of a reliable technique for synchronization of the kinetoplastids should not only permit a detailed analysis of their cellular and molecular biology but provide a means to collect and characterize biochemical and immunochemical substances relevant to the infectious process. (C) 1994 Academic Press, Inc. C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. RP GALANTI, N (reprint author), UNIV CHILE,SCH MED,DEPT CELL BIOL & GENET,SANTIAGO 7,CHILE. RI Galanti, Norbel/H-9747-2013 OI Galanti, Norbel/0000-0001-6360-7019 NR 38 TC 30 Z9 30 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD SEP PY 1994 VL 214 IS 1 BP 225 EP 230 DI 10.1006/excr.1994.1252 PG 6 WC Oncology; Cell Biology SC Oncology; Cell Biology GA PF634 UT WOS:A1994PF63400026 PM 8082726 ER PT J AU JONES, BE MOSHYEDI, P GALLO, S TOMBRANTINK, J ARAND, G REID, DA THOMPSON, EW CHADER, GJ WALDBILLIG, RJ AF JONES, BE MOSHYEDI, P GALLO, S TOMBRANTINK, J ARAND, G REID, DA THOMPSON, EW CHADER, GJ WALDBILLIG, RJ TI CHARACTERIZATION AND NOVEL ACTIVATION OF 72-KDA METALLOPROTEINASE IN RETINAL INTERPHOTORECEPTOR MATRIX AND Y-79 CELL-CULTURE MEDIUM SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE GELATINASE; METALLOPROTEINASE; STROMELYSIN; INTER-PHOTORECEPTOR MATRIX; Y-79 RETINOBLASTOMA CELL; TISSUE INHIBITOR OF METALLOPROTEINASE ID BASEMENT-MEMBRANE COLLAGEN; TISSUE INHIBITOR; IV COLLAGENASE; CONE PHOTORECEPTORS; PIGMENT-EPITHELIUM; BINDING PROTEIN; LIGHT; RETINOBLASTOMA; IDENTIFICATION; GELATINASE AB Analysis of bovine interphotoreceptor matrix and conditioned medium from human Y-79 retinoblastoma cells by gelatin SDS-PAGE zymography reveals abundant activity of a 72-kDa M(r) gelatinase. The 72-kDa gelatinase from either source is inhibited by EDTA but not aprotinin or NEM, indicating that it is a metalloproteinase (MMP). The 72-kDa MMP is converted to a 62-kDa species with APMA treatment after gelatin sepharose affinity purification, typical of previously described gelatinase MMP-2. The latent 72-kDa gelatinase from either bovine IPM or Y-79 media autoactivates without APMA in the presence of calcium and zinc after 72 hr at 37 degrees C, producing a fully active mixture of proteinase species, 50 (48 in Y-79 medium), 38 and 35 kDa in size. The presence of inhibitory activity was examined in both whole bovine IPM and IPM fractions separated by SDS-PAGE. Whole IPM inhibited gelatinolytic activity of autoactivated Y-79-derived MMP in a dose-dependent manner. Inhibitory activities are observed in two protein fractions of 27-42 and 20-25 kDa. Western blots using antibodies to human tissue inhibitor of metalloproteinase 1 and 2 (TIMP-1 and -2) reveal the presence of two TIMP-1-like proteins at 21 and 29 kDa in inhibitory fractions of the bovine IPM. TIMP-2 was not detected in the inhibitory IPM fractions, consistent with the observed autoactivation of bovine IPM 72-kDa gelatinase. Potential roles for this IPM MMP-TIMP system include physiologic remodelling of the neural retina-RPE cell interface and digestion of shed rod outer segment as well as pathological processes such as retinal detachment, PE cell migration, neovascularization and tumor progression, Cultured Y-79 cells appear to be a good model for studying the production and regulation of this proteinase system. C1 GEORGETOWN UNIV,SCH MED,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. GEORGETOWN UNIV,SCH MED,DEPT CELL BIOL,WASHINGTON,DC 20007. RP JONES, BE (reprint author), NEI,RETINAL CELL & MOLEC BIOL LAB,BLDG 6,ROOM 310,BETHESDA,MD 20892, USA. RI Thompson, Erik/A-1425-2009 OI Thompson, Erik/0000-0002-9723-4924 NR 55 TC 18 Z9 18 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD SEP PY 1994 VL 59 IS 3 BP 257 EP 269 DI 10.1006/exer.1994.1107 PG 13 WC Ophthalmology SC Ophthalmology GA PK975 UT WOS:A1994PK97500002 PM 7821370 ER PT J AU PFEFFER, BA FLANDERS, KC GUERIN, CJ DANIELPOUR, D ANDERSON, DH AF PFEFFER, BA FLANDERS, KC GUERIN, CJ DANIELPOUR, D ANDERSON, DH TI TRANSFORMING GROWTH-FACTOR-BETA-2 IS THE PREDOMINANT ISOFORM IN THE NEURAL RETINA, RETINAL-PIGMENT EPITHELIUM-CHOROID AND VITREOUS OF THE MONKEY EYE SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE TRANSFORMING GROWTH FACTOR BETA; RETINAL PIGMENT EPITHELIUM, PHOTORECEPTOR; MONKEY; IMMUNOCYTOCHEMISTRY; EPITHELIAL CELL CULTURE ID LINKED IMMUNOSORBENT ASSAYS; MOLECULAR-WEIGHT COMPLEX; TGF-BETA; IMMUNOHISTOCHEMICAL LOCALIZATION; INTERPHOTORECEPTOR MATRIX; CELL-PROLIFERATION; ENDOTHELIAL-CELLS; BINDING PROTEIN; HUMAN-PLATELETS; IDENTIFICATION AB Several techniques were utilized to assess the levels, disposition and cellular sources of isoforms 1 and 2 of transforming growth factor beta (TGF-beta) in the posterior pole of the monkey eye. Freshly dissected tissues, as well as the saline vehicles in which dissections were performed, were analysed by sandwich enzyme-linked immunosorbent assay. In all tissues TGF-beta 2 was the predominant isoform, with beta 2:beta 1 ratios of 6:1 for neural retina (as ng g(-1)) and 425:1 for vitreous (as pmol l(-1)). Retinal pigment epithelium (RPE)-Bruch's membrane-choroid complex contained approximately 10 times the amount of both TGF-beta isoforms as neural retina. For first passage cultures of monkey RPE, TGF-beta 2, but not TGF-beta 1, accumulated over time in conditioned media samples. Immunoreactivity for TGF-beta 2 was detected both in tissue sections of posterior pole, specifically in rod outer segments and RPE, and also in the first passage cultures of RPE. Antibodies to specific peptide sequences of both isoforms localized TGF-beta to the outer segments of rod photoreceptors. The apparent sequestration of TGF-beta 2 in photoreceptor outer segments, as well as the in vitro evidence for possible synthesis and release by RPE, suggest that TGF-beta 2 is an important modulator of visual function acting at the retina-RPE interface. C1 NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. UNIV CALIF SANTA BARBARA,INST NEUROSCI,SANTA BARBARA,CA 93106. FU NEI NIH HHS [EY 02082] NR 51 TC 100 Z9 103 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD SEP PY 1994 VL 59 IS 3 BP 323 EP 333 DI 10.1006/exer.1994.1114 PG 11 WC Ophthalmology SC Ophthalmology GA PK975 UT WOS:A1994PK97500009 PM 7821377 ER PT J AU GRAHAM, C WISTOW, G AF GRAHAM, C WISTOW, G TI THE PREDOMINANT CADHERIN IN FETAL HUMAN LENS IS IDENTICAL TO N-CADHERIN AND IS NOT A CANDIDATE LOCUS FOR THE MARNER CATARACT SO EXPERIMENTAL EYE RESEARCH LA English DT Letter ID CELL-ADHESION MOLECULES; MOUSE CHROMOSOME-8; ENDOTHELIAL-CELLS; CRYSTALLIN GENE; EYE LENS; UVOMORULIN; MUTATION; DELETION; PANEL-2; MAPS C1 NEI,LMDB,MOLEC STRUCT & FUNCT SECT,BETHESDA,MD 20892. NR 23 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD SEP PY 1994 VL 59 IS 3 BP 373 EP 376 DI 10.1006/exer.1994.1120 PG 4 WC Ophthalmology SC Ophthalmology GA PK975 UT WOS:A1994PK97500015 PM 7821383 ER PT J AU JACOBSEN, SEW RUSCETTI, FW ORTIZ, M GOOYA, JM KELLER, JR AF JACOBSEN, SEW RUSCETTI, FW ORTIZ, M GOOYA, JM KELLER, JR TI THE GROWTH-RESPONSE OF LIN(-)THY-1(+) HEMATOPOIETIC PROGENITORS TO CYTOKINES IS DETERMINED BY THE BALANCE BETWEEN SYNERGY OF MULTIPLE STIMULATORS AND NEGATIVE COOPERATION OF MULTIPLE INHIBITORS SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE HEMATOPOIESIS; INHIBITORS; STIMULATORS ID TUMOR-NECROSIS-FACTOR; STEM-CELL FACTOR; COLONY FORMATION INVITRO; FACTOR-BETA; FACTOR-ALPHA; TGF-BETA; BFU-E; MURINE; PROLIFERATION; IDENTIFICATION AB The present studies investigated the balance of positive and negative growth signals in direct regulation of hematopoiesis. Interleukin-3 (IL-3) combined with Steel factor (SLF) optimally stimulated proliferation of Lin(-)Thy-1(+) murine bone marrow progenitors in single-cell assays, and that proliferation was inhibited more than 90% by transforming growth factor-beta 1 (TGF-beta 1). Colony-stimulating factor-1 (CSF-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-1, or IL-6 as a third stimulatory growth factor was incapable of counteracting the TGF-beta 1-mediated inhibition of IL-3-plus-SLF-stimulated growth, while G-CSF slightly enhanced the number of TGF-beta 1-resistant clones. As a fourth factor, only IL-1 could partially overcome the TGF-beta 1-induced growth inhibition. While the presence of a cocktail of five additional stimulatory growth factors did not enhance the frequency of single Lin(-)Thy-1(+) progenitors proliferating in response to IL-3 plus SLF, the number of responding progenitors in the presence of TGF-beta 1 was enhanced nine-fold. Furthermore, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), but not macrophage inflammatory protein-1 alpha (MIP-1 alpha), cooperated with TGF-beta 1 to reverse the proliferative effects of multiple stimulatory cytokines, resulting in 76% inhibition. Thus, the direct effects of single inhibitory factors on hematopoietic progenitor cell growth can be reversed by multiple stimulatory growth factors, and negative growth factors can directly cooperate to suppress progenitor cell growth stimulated by multiple positive-acting factors. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,LEUKOCYTE BIOL LAB,FREDERICK,MD 21702. FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21701. RP JACOBSEN, SEW (reprint author), NORWEGIAN RADIUM HOSP,INST CANC RES,DEPT IMMUNOL,N-0310 OSLO,NORWAY. FU NCI NIH HHS [N01-CO-74102] NR 40 TC 37 Z9 39 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 1994 VL 22 IS 10 BP 985 EP 989 PG 5 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA PG272 UT WOS:A1994PG27200007 PM 7522186 ER PT J AU BLASI, E PULITI, M PITZURRA, L BARLUZZI, R MAZZOLLA, R ADAMI, C COX, GW BISTONI, F AF BLASI, E PULITI, M PITZURRA, L BARLUZZI, R MAZZOLLA, R ADAMI, C COX, GW BISTONI, F TI COMPARATIVE-STUDIES ON FUNCTIONAL AND SECRETORY PROPERTIES OF MACROPHAGE CELL-LINES DERIVED FROM DIFFERENT ANATOMICAL SITES SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article DE MACROPHAGE; CYTOKINE; FUNCTIONAL HETEROGENEITY ID TUMOR-NECROSIS-FACTOR; CANDIDA-ALBICANS; AMEBOID MICROGLIA; BONE-MARROW; INTERLEUKIN-1; IMMORTALIZATION; RETROVIRUS; EXPRESSION; SEQUENCE; MEDIATOR AB In the present study, we compared four macrophage (M phi) cell lines from different anatomical origins for functional and secretory activities against the two morphogenetic forms of the fungus Candida albicans. We show that all the cell lines actively phagocytize the yeast and exert antimicrobial activity against both forms of Candida, although M phi of microglial origin are the most effective. When assessed for secretory properties, microglial M phi exhibit a peculiar pattern with respect to other M phi populations under either basal or stimulated conditions. In particular, only microglial M phi fail to respond to the hyphal form of the fungus (H-Candida), which instead acts as a potent tumor necrosis factor inducer in the other M phi cell lines. When exposed to H-Candida, microglial M phi are indistinguishable from other M phi in their ability to modulate specific surface adhesion molecules. In addition to strengthening the knowledge on functional heterogeneity among M phi, our data provide evidence on the peculiar behavior of microglial M phi. To what extent M phi heterogeneity may be related to tissue homeostasis is discussed. C1 NCI,FREDERICK CANC RES & DEV CTR,MACROPHAGE CELL BIOL LAB,FREDERICK,MD. RP BLASI, E (reprint author), UNIV PERUGIA,DEPT EXPTL MED & BIOCHEM SCI,VIA GIOCHETTO,I-06100 PERUGIA,ITALY. RI Blasi, Elisabetta/F-5870-2015; OI Blasi, Elisabetta/0000-0002-4202-8293; Pitzurra, Lucia/0000-0002-6866-7982 NR 34 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD SEP PY 1994 VL 9 IS 3 BP 207 EP 215 DI 10.1111/j.1574-695X.1994.tb00495.x PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PH574 UT WOS:A1994PH57400006 PM 7529080 ER PT J AU KARI, FW BUCHER, J HASEMAN, JK HUFF, JE AF KARI, FW BUCHER, J HASEMAN, JK HUFF, JE TI SOME COMMENTS ON THE POTENTIAL EFFECTS OF HYDROQUINONE EXPOSURE - REPLY SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Letter RP KARI, FW (reprint author), NIEHS,PUBL HLTH SERV,DEPT HLTH & HUMAN SERV,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD SEP PY 1994 VL 32 IS 9 BP 866 EP 867 PG 2 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA PJ556 UT WOS:A1994PJ55600012 ER PT J AU BENCHEKROUN, MN MYERS, CE SINHA, BK AF BENCHEKROUN, MN MYERS, CE SINHA, BK TI FREE-RADICAL FORMATION BY ANSAMYCIN BENZOQUINONE IN HUMAN BREAST-TUMOR CELLS - IMPLICATIONS FOR CYTOTOXICITY AND RESISTANCE SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE GELDANAMYCIN; HERBIMYCIN A; ADRIAMYCIN; SPIN-TRAPPING; ESR; FREE RADICAL; MULTIDRUG RESISTANCE; P-170-GLYCOPROTEIN ID ELECTRON-SPIN RESONANCE; INDUCED LIPID-PEROXIDATION; GLUTATHIONE-PEROXIDASE; DRUG-RESISTANCE; CANCER-CELLS; OXYGEN; DOXORUBICIN; ADRIAMYCIN; MECHANISM; LINES AB The benzoquinonoid ansamycin antibiotics, geldanamycin and herbimycin A, are potent cytotoxins against tumor cells in vitro. We have examined the mechanism of their in vitro cytotoxicity against human breast adenocarcinoma (MCF-7) cells and we have found that multidrug-resistant MCF-7/ADR(R) cells that exhibit the MDR phenotype and the overexpression of P-170-glycoprotein, were cross-resistant to geldanamycin and herbimycin A. Verapamil, which binds competitively with P-170-glycoprotein, enhanced geldanamycin cytotoxicity 12-fold only in resistant cells, suggesting that geldanamycin may interact with the drug efflux protein. Geldanamycin and herbimycin A, like adriamycin, were reductively activated by the NADPH-cytochrome P450-reductase and formed reactive (OH)-O-.. The formation of (OH)-O-. was significantly lower in resistant cells. In contrast to adriamycin, the formation of (OH)-O-. was unaffected by the addition of DNA, indicating that a DNA-complexed drug was redox-active and may, therefore, may be more effective in killing tumor cells at the DNA level. These observations indicate that both the decreased free radical formation and interactions with P170 glycoprotein may be important in geldanamycin and herbimycin A resistance in multidrug resistant human breast tumor cells. C1 NCI,CLIN PHARMACOL BRANCH,BIOCHEM & MOLEC PHARMACOL SECT,BETHESDA,MD 20892. NR 37 TC 23 Z9 24 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD SEP PY 1994 VL 17 IS 3 BP 191 EP 200 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA PC661 UT WOS:A1994PC66100001 ER PT J AU WARNER, HR AF WARNER, HR TI SUPEROXIDE-DISMUTASE, AGING, AND DEGENERATIVE DISEASE SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Review DE SUPEROXIDE DISMUTASE; AGING; OXIDATIVE DAMAGE; ANTIOXIDANT DEFENSE; AMYOTROPHIC LATERAL SCLEROSIS; LIFE SPAN; FREE RADICAL ID TUMOR-NECROSIS-FACTOR; AMYOTROPHIC-LATERAL-SCLEROSIS; AGE-RELATED-CHANGES; TRANSGENIC MICE; GLUTATHIONE-PEROXIDASE; DROSOPHILA-MELANOGASTER; OXIDATIVE STRESS; RAT-BRAIN; LIFE-SPAN; ANTIOXIDANT DEFENSES AB Over 15 years of research on correlations between superoxide dismutase (SOD) activity and aging or life span have failed to provide a consistent picture of the role of SOD in aging. While genetic manipulations that increase CuZn-SOD activity have only a slight, if any, effect on maximum life span in several species, they do increase resistance to oxidative stress. However, increasing both CuZn-SOD and catalase does significantly increase maximum life span. Decreased SOD expression in a variety of species increases their vulnerability to oxidative stress, and in the case of genetically altered CuZn-SOD, leads to premature death of motor neurons in humans. Little is known about the regulation of expression of SOD and other antioxidant defense enzymes in eukaryotes. The research summarized below collectively suggest that SOD plays an important role in longevity and degenerative disease, but much remains to be learned before manipulation of SOD expression can be considered for effective intervention in either process. RP WARNER, HR (reprint author), NIA,BIOL AGING PROGRAM,BLDG 31,BETHESDA,MD 20892, USA. NR 93 TC 157 Z9 161 U1 3 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD SEP PY 1994 VL 17 IS 3 BP 249 EP 258 DI 10.1016/0891-5849(94)90080-9 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA PC661 UT WOS:A1994PC66100007 PM 7982630 ER PT J AU ZEIGER, MA GNARRA, JR ZBAR, B LINEHAN, WM PASS, HI AF ZEIGER, MA GNARRA, JR ZBAR, B LINEHAN, WM PASS, HI TI LOSS OF HETEROZYGOSITY ON THE SHORT ARM OF CHROMOSOME-3 IN MESOTHELIOMA CELL-LINES AND SOLID TUMORS SO GENES CHROMOSOMES & CANCER LA English DT Article ID HUMAN-MALIGNANT MESOTHELIOMA; MOLECULAR ANALYSIS; SUPPRESSOR GENES; ABNORMALITIES; CARCINOMA; CANCER; LUNG AB Cytogenetic analysis of mesothelioma cell lines and solid tumors has documented non-random chromosomal abnormalities on the short arm of chromosome 3 from 3p14 to 3p25. We therefore examined nine mesothelioma cell lines, their corresponding tumors, and 15 additional mesothelioma tumors for loss of heterozygosity on 3p from 3p13 to 3p25.5 by polymerase chain reaction and restriction fragment length polymorphism analysis at 8 loci: D3S3, D3S30, D3S6, D3S2, D3S32, D3F15S2, THRB, and VHL. Loss of heterozygosity was documented by loss of one of two alleles in the tumor DNA whose corresponding normal DNA was heterozygous and was documented in four of nine mesothelioma cell lines and six of 15 mesothelioma tumors or a total of 42% of the mesotheliomas evaluated. This study suggests the involvement of a gene on the short arm of chromosome 3 in the development of mesotheliomas. (C) 1994 Wiley-Liss, Inc. C1 NCI,DIV CANC TREATMENT,SURG BRANCH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC BIOL & DIAG,IMMUNOBIOL LAB,FREDERICK,MD. NR 15 TC 30 Z9 30 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD SEP PY 1994 VL 11 IS 1 BP 15 EP 20 DI 10.1002/gcc.2870110104 PG 6 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA PD822 UT WOS:A1994PD82200003 PM 7529042 ER PT J AU LOUIS, JM GINSBURG, GT KIMMEL, AR AF LOUIS, JM GINSBURG, GT KIMMEL, AR TI THE CAMP RECEPTOR CAR4 REGULATES AXIAL PATTERNING AND CELLULAR-DIFFERENTIATION DURING LATE DEVELOPMENT OF DICTYOSTELIUM SO GENES & DEVELOPMENT LA English DT Article DE CAMP; DIFFERENTIATION; RECEPTORS; GENE EXPRESSION ID GENE-EXPRESSION; INOSITOL TRISPHOSPHATE; DISCOIDEUM; CHEMOATTRACTANT; ACCUMULATION; IDENTIFICATION; MECHANISMS; SEQUENCES; PRESPORE; SLUGS AB Pseudoplasmodia of developing Dictyostelium are organized with anteroposterior polarity. We have isolated CAR4, the gene for a new cell-surface, G protein-linked cAMP receptor. CAR4 mRNA is initially expressed during tip elongation and continues to accumulate into culmination. CAR4 is maximally expressed in pseudoplasmodia anteriors which are centers for extracellular cAMP signaling and for organization of cellular patterning. Although car4 null cells progress unperturbed through early development, they exhibit major patterning aberrations as the anteroposterior axis becomes established. Prestalk gene expression is significantly reduced in car4 nulls, whereas prespore-specific markers are overexpressed and detected in zones normally restricted to prestalk cells. Patterning defects are similarly apparent in terminally differentiated fruiting bodies. Our results show that cAMP signaling is required for pattern formation and cellular differentiation during late Dictyostelium development. RP LOUIS, JM (reprint author), NIDDKD,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892, USA. NR 42 TC 66 Z9 69 U1 0 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 SEP 1 PY 1994 VL 8 IS 17 BP 2086 EP 2096 DI 10.1101/gad.8.17.2086 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA PF914 UT WOS:A1994PF91400008 PM 7958880 ER PT J AU THON, G COHEN, A KLAR, AJ AF THON, G COHEN, A KLAR, AJ TI 3 ADDITIONAL LINKAGE GROUPS THAT REPRESS TRANSCRIPTION AND MEIOTIC RECOMBINATION IN THE MATING-TYPE REGION OF SCHIZOSACCHAROMYCES-POMBE SO GENETICS LA English DT Article ID FISSION YEAST; SACCHAROMYCES-CEREVISIAE; DNA ELEMENTS; EXPRESSION; GENES; CASSETTES; TRANSPOSITION; SILENCERS; CLONING; LOCUS AB The mating-type genes of Schizosaccharomyces pombe are found at three locations in the same chromosomal region. These genes are in an active configuration at the mat1 locus and in an inactive configuration at the mat2 and mat3 loci. The mechanism that represses transcription of mat2 and mat3 also inactivates other promoters introduced nearby and is accompanied by a block to meiotic recombination in the mat2-mat3 interval, suggesting that this mechanism involves a particular chromatin structure. We present evidence that the transcription and recombination blocks require three newly defined trans-acting loci, clr2, clr3 and clr4, in addition to the previously identified clr1, rik1 and swi6 loci. We also investigated the role of mat2 cis-acting sequences in silencing. Four cis-acting elements that repress mat2 in a plasmid context were previously identified. Deletion of two of these elements proved to have little effect in a chromosomal context. However, when combined with mutations in trans-acting genes, deletion of the same two elements greatly enhanced mat2 expression. The observed cumulative effects suggest a redundancy in the silencing mechanism. C1 NCI, FREDERICK CANC RES & DEV CTR,ABL, BASIC RES PROGRAM,EUKARYOT GENE EXPRESS LAB, FREDERICK, MD 21702 USA. RI Thon, Genevieve/L-9497-2014 OI Thon, Genevieve/0000-0001-8550-5945 FU NCI NIH HHS [N01-CO-74101] NR 44 TC 96 Z9 96 U1 0 U2 0 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD SEP PY 1994 VL 138 IS 1 BP 29 EP 38 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA PC818 UT WOS:A1994PC81800004 PM 8001791 ER PT J AU HENTHORN, PS SOMBERG, RL FIMIANI, VM PUCK, JM PATTERSON, DF FELSBURG, PJ AF HENTHORN, PS SOMBERG, RL FIMIANI, VM PUCK, JM PATTERSON, DF FELSBURG, PJ TI IL-2R-GAMMA GENE MICRODELETION DEMONSTRATES THAT CANINE X-LINKED SEVERE COMBINED IMMUNODEFICIENCY IS A HOMOLOG OF THE HUMAN-DISEASE SO GENOMICS LA English DT Article ID RECEPTOR GAMMA-CHAIN; CHROMOSOME INACTIVATION; FUNCTIONAL COMPONENT; DEFICIENT RABBITS; IL-2 RECEPTOR; CARRIERS; SCIDX1; CELLS; HYPERCHOLESTEROLEMIA; IMPROVEMENT AB X-linked severe combined immunodeficiency (SCID) is characterized by profound defects in cellular and humoral immunity and, in humans, is associated with mutations in the gene for the gamma chain of the IL-2 receptor (IL-2R gamma). We have examined this gene in a colony of dogs established from a single X-linked SCID carrier female. Affected dogs have a 4-bp deletion in the first exon of the IL-2R gamma gene, which precludes the production of a functional protein, demonstrating that the canine disease is a true homologue of human X-linked SCID. (C) 1994 Academic Press, Inc. C1 UNIV PENN,SCH VET MED,DEPT CLIN STUDIES,IMMUNOL SECT,PHILADELPHIA,PA 19104. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP HENTHORN, PS (reprint author), UNIV PENN,SCH VET MED,DEPT CLIN STUDIES,MED GENET SECT,3850 SPRUCE ST,PHILADELPHIA,PA 19104, USA. FU NCRR NIH HHS [RR02512]; NIAID NIH HHS [AI33177, AI26103] NR 37 TC 98 Z9 101 U1 1 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD SEP 1 PY 1994 VL 23 IS 1 BP 69 EP 74 DI 10.1006/geno.1994.1460 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PG072 UT WOS:A1994PG07200009 PM 7829104 ER PT J AU KAMB, A FUTREAL, PA ROSENTHAL, J COCHRAN, C HARSHMAN, KD LIU, QY PHELPS, RS TAVTIGIAN, SV TRAN, T HUSSEY, C BELL, R MIKI, Y SWENSEN, J HOBBS, MR MARKS, J BENNETT, LM BARRETT, JC WISEMAN, RW SHATTUCKEIDENS, D AF KAMB, A FUTREAL, PA ROSENTHAL, J COCHRAN, C HARSHMAN, KD LIU, QY PHELPS, RS TAVTIGIAN, SV TRAN, T HUSSEY, C BELL, R MIKI, Y SWENSEN, J HOBBS, MR MARKS, J BENNETT, LM BARRETT, JC WISEMAN, RW SHATTUCKEIDENS, D TI LOCALIZATION OF THE VHR PHOSPHATASE CANE AND ITS ANALYSIS AS A CANDIDATE FOR BRCA1 SO GENOMICS LA English DT Article ID FAMILIAL BREAST; OVARIAN-CANCER; GENE; CHROMOSOME-17Q; LINKAGE; TUMORIGENICITY; RETINOBLASTOMA; EXPRESSION AB The VH1-related human protein (VHR) gene was localized to human chromosome 17q21 in a region thought to contain the BRCA1 locus, a locus that confers susceptibility to breast and ovarian cancer. VHR encodes a phosphatase with dual specificity for tyrosine and serine residues. Thus it is a plausible candidate for a tumor suppressor gene such as BRCA1. To test this possibility, the VHR coding sequence was screened in individuals with familial breast cancer and in sporadic breast tumor and breast cancer cell lines. No mutations were detected, suggesting that the VHR gene is not BRCA1. (C) 1994 Academic Press,Inc. C1 NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. DUKE UNIV,MED CTR,DEPT SURG,DURHAM,NC 27710. UNIV UTAH,DEPT GENET EPIDEMIOL,SALT LAKE CITY,UT 84108. RP KAMB, A (reprint author), MYRIAD GENET INC,421 WAKARA WAY,SALT LAKE CITY,UT 84108, USA. FU NCI NIH HHS [CA-55914, CA-48711] NR 18 TC 11 Z9 11 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD SEP 1 PY 1994 VL 23 IS 1 BP 163 EP 167 DI 10.1006/geno.1994.1473 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PG072 UT WOS:A1994PG07200022 PM 7829067 ER PT J AU JANIS, EM SILICIANO, JD ISAAC, DD GRIFFIN, CA HAWKINS, AL KOZAK, CA DESIDERIO, S AF JANIS, EM SILICIANO, JD ISAAC, DD GRIFFIN, CA HAWKINS, AL KOZAK, CA DESIDERIO, S TI MAPPING OF THE GENE FOR THE TYROSINE KINASE-ITK TO A REGION OF CONSERVED SYNTENY BETWEEN MOUSE CHROMOSOME-11 AND HUMAN-CHROMOSOME-5Q SO GENOMICS LA English DT Note ID X-LINKED AGAMMAGLOBULINEMIA; INSITU HYBRIDIZATION; EXPRESSION; LEUKEMIA; CLONING AB The protein-tyrosine kinase gene Itk is expressed preferentially in T lymphoid cells of the mouse and is induced by IL-2. A related gene, Btk, is expressed in the murine B lymphoid and myeloid lineages. Because mutations in Btk and the corresponding human gene are associated with X-linked immunodeficiency syndromes, it was of interest to map Itk and its human counterpart. By Southern blot analysis of DNA from the progeny of two multilocus crosses, murine Itk was mapped to Chromosome 11. By fluorescence in situ hybridization, human ITK was mapped to 5q32-q33. Murine Itk and its human homologue lie within regions of conserved synteny that include several growth factor and growth factor receptor genes. This region in humans is frequently deleted in the myelodysplastic syndrome, suggesting possible involvement of ITK in this disorder. (C) 1994 Academic Press, Inc. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MOLEC BIOL & GENET,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,HOWARD HUGHES MED INST,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT ONCOL,BALTIMORE,MD 21205. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA16519, CA06973]; NHGRI NIH HHS [HG00373] NR 20 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD SEP 1 PY 1994 VL 23 IS 1 BP 269 EP 271 DI 10.1006/geno.1994.1492 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PG072 UT WOS:A1994PG07200041 PM 7829087 ER PT J AU BOISCLAIR, YR YANG, YWH STEWART, JM RECHLER, MM AF BOISCLAIR, YR YANG, YWH STEWART, JM RECHLER, MM TI INSULIN-LIKE GROWTH-FACTOR-I AND INSULIN STIMULATE THE SYNTHESIS OF IGF-BINDING PROTEIN-2, IN A HUMAN EMBRYONIC KIDNEY-CELL LINE SO GROWTH REGULATION LA English DT Article DE IGFBP-2 SYNTHESIS; PROTEIN SYNTHESIS; 293 CELLS ID BREAST-CANCER CELLS; RAT HEPATOMA-CELLS; GENE-EXPRESSION; MESSENGER-RNA; HUMAN FIBROBLASTS; BIOLOGICAL-ACTIVITIES; LIVER; TRANSCRIPTION; RECEPTOR; PROMOTER AB Insulin and insulin-like growth factor (IGF)-I are thought to be major metabolic regulators of IGF-binding protein-2 (IGFBP-2). We have examined the regulation of IGFBP-2 expression by IGF-I and insulin in 293 cells, a cell line derived from human embryonic kidney. The predominant 34 kDa IGFBP in media conditioned by unstimulated 293 cells was identified as IGFBP-2 by immunoprecipitation. IGFBP-2 levels were increased 6 to 7-fold following incubation with IGF-I, IGF-II or insulin for 48 h. A corresponding increase in IGFBP-2 mRNA was not observed, suggesting that regulation occurred at the translational or post-translational level. The stimulation of IGFBP-2 by IGF-I and insulin was reversibly abolished by incubation with protein synthesis inhibitors such as cycloheximide. Biosynthetic labeling of quiescent 293 cells using [S-35]cysteine indicated that incubation with insulin or IGF-I for 24h increased the synthesis of total cell proteins (predominantly intracellular) and IGFBP-2 (predominantly secreted) to a similar extent (2- to 4-fold). These results suggest that the increase in IGFBP-2 secreted by 293 cells after incubation with IGF-I or insulin largely results from a general stimulation of protein synthesis. RP BOISCLAIR, YR (reprint author), NIDDK,MOLEC & CELLULAR ENDOCRINOL BRANCH,GROWTH & DEV SECT,BETHESDA,MD 20892, USA. NR 67 TC 14 Z9 14 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0956-523X J9 GROWTH REGULAT JI Growth Regul. PD SEP PY 1994 VL 4 IS 3 BP 136 EP 146 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PT477 UT WOS:A1994PT47700007 PM 7532054 ER PT J AU SILBERBERG, M ESTES, CL HARRINGTON, C AF SILBERBERG, M ESTES, CL HARRINGTON, C TI POLITICAL PERSPECTIVES ON UNCERTIFIED HOME CARE AGENCIES SO HEALTH CARE FINANCING REVIEW LA English DT Article ID QUALITY AB This article examines the political agendas of public sector and organized private sector interests concerned with policies affecting uncertified home care agencies in three metropolitan areas. Using a telephone survey, the study found substantial differences across these groups in both the frequency with which they work on given issues and in some key attitudes. Overall, respondents were most likely to work on Policies related to home care quality, and had Particularly diverse-and at times conflicting-concerns in this area. Policymakers need to actively solicit the diverse attitudes of key interest groups towards controversial issues in order to understand less dominant perspectives, keep in mind the interconnection of policy issues, and arrive at politically viable solutions to home care policy problems. C1 NIA,BETHESDA,MD 20892. RP SILBERBERG, M (reprint author), UNIV CALIF SAN FRANCISCO,INST HLTH & AGING,N-631,SAN FRANCISCO,CA 94143, USA. FU AHRQ HHS [R0I HS06860-02] NR 31 TC 1 Z9 1 U1 0 U2 0 PU HEALTH CARE FINANCING REVIEW PI BALTIMORE PA ROOM 1-A-9 OAK MEADOWS BLDG 6325 SECURITY BLVD, BALTIMORE, MD 21207 SN 0195-8631 J9 HEALTH CARE FINANC R JI Health Care Finan. Rev. PD FAL PY 1994 VL 16 IS 1 BP 223 EP 245 PG 23 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA RY207 UT WOS:A1994RY20700011 PM 10140155 ER PT J AU STECKLER, AB SIMONSMORTON, B GOTTLIEB, N AF STECKLER, AB SIMONSMORTON, B GOTTLIEB, N TI UNTITLED SO HEALTH EDUCATION RESEARCH LA English DT Editorial Material C1 NICHHD,BETHESDA,MD 20892. UNIV TEXAS,DEPT KINESIOL & HLTH EDUC,AUSTIN,TX 78712. FELIX & BURDINE INC,ALLENTOWN,PA 18103. RP STECKLER, AB (reprint author), UNIV N CAROLINA,DEPT HLTH BEHAV & HLTH EDUC,CHAPEL HILL,NC 27599, USA. NR 2 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 0268-1153 J9 HEALTH EDUC RES JI Health Educ. Res. PD SEP PY 1994 VL 9 IS 3 BP 271 EP 272 DI 10.1093/her/9.3.271 PG 2 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA PG491 UT WOS:A1994PG49100001 ER PT J AU EISSA, NT CHU, CS DANEL, C CRYSTAL, RG AF EISSA, NT CHU, CS DANEL, C CRYSTAL, RG TI EVALUATION OF THE RESPIRATORY EPITHELIUM OF NORMALS AND INDIVIDUALS WITH CYSTIC-FIBROSIS FOR THE PRESENCE OF ADENOVIRUS E1A SEQUENCES RELEVANT TO THE USE OF E1A(-) ADENOVIRUS VECTORS FOR GENE-THERAPY FOR THE RESPIRATORY MANIFESTATIONS OF CYSTIC-FIBROSIS SO HUMAN GENE THERAPY LA English DT Article ID CONDUCTANCE REGULATOR GENE; DNA-SEQUENCES; INVIVO; IDENTIFICATION; EXPRESSION; INFECTION; VIRUS; INVITRO; TYPE-5; CELLS AB Lung disease associated with disorders such as cystic fibrosis (CF) may be amenable to somatic gene therapy in which there is delivery of the normal gene directly to the respiratory epithelium using E1a(-) adenovirus (Ad) type 2- or 5-based vectors. For safety reasons, the Ad vectors are rendered replication deficient by deletion of the E1a region. Because there is the theoretical possibility of an E1a(-) replication-deficient vector replicating as a result of recombination or complementation with Ad 2/5 E1a sequences present in the target cell, this study is directed toward evaluating respiratory epithelium of normals and individuals with CF for the presence of E1a sequences. Using Ad 2/5 E1a-specific primers and the polymerase chain reaction to evaluate DNA recovered from freshly isolated nasal and bronchial epithelium recovered by brushing, E1a sequences were detected in respiratory epithelium of 19 of 91 normals (21%). In the E1a-positive samples, the average of E1a copy number was 55 +/- 18/10(3) recovered cells. In CF individuals, 7 of 52 (13%) had detectable E1a sequences in the respiratory epithelium, with E1a copy number in the positive samples of 80 +/- 21/10(3) recovered cells. These results demonstrate that there are detectable Ad 2/5 E1a sequences in the respiratory epithelium of a small percentage of normals and individuals with CF. Because of the theoretical potential of such sequences supporting replication of E1a(-) Ad vectors, human gene therapy protocols for CF utilizing such vectors should consider evaluating study individuals for the presence of Ad 2/5 E1a sequences in the respiratory epithelium. C1 CORNELL UNIV,COLL MED,DIV PULM & CRIT CARE MED,NEW YORK,NY 10021. RP EISSA, NT (reprint author), NHLBI,PULM BRANCH,ROOM 6D03,BLDG 10,BETHESDA,MD 20892, USA. NR 35 TC 24 Z9 24 U1 0 U2 1 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 SEP PY 1994 VL 5 IS 9 BP 1105 EP 1114 DI 10.1089/hum.1994.5.9-1105 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA PG774 UT WOS:A1994PG77400005 PM 7833370 ER PT J AU ROSENFELD, MA ROSENFELD, SJ DANEL, C BANKS, TC CRYSTAL, RG AF ROSENFELD, MA ROSENFELD, SJ DANEL, C BANKS, TC CRYSTAL, RG TI INCREASING EXPRESSION OF THE NORMAL HUMAN CFTR CDNA IN CYSTIC-FIBROSIS EPITHELIAL-CELLS RESULTS IN A PROGRESSIVE INCREASE IN THE LEVEL OF CFTR PROTEIN EXPRESSION, BUT A LIMIT ON THE LEVEL OF CAMP-STIMULATED CHLORIDE SECRETION SO HUMAN GENE THERAPY LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; MEDIATED GENE-TRANSFER; TRANSPORT; IDENTIFICATION; CHANNEL; INVIVO; DNA; CORRECTS; DEFECT; ASSAY AB Cystic fibrosis (CF) results from mutations of the CF transmembrane conductance regulator (CFTR) gene and the consequent defective regulation of cAMP-stimulated Cl- permeability across epithelial cell apical membranes. Given that in vitro transfer of normal CFTR cDNA corrects this defect and that recombinant adenovirus (Ad) vectors can transfer the normal human CFTR cDNA in vivo, Ad vectors have significant potential in the development of effective strategies for CF gene therapy. One concern is whether CFTR overexpression achievable with Ad vectors may have untoward effects on cAMP-stimulated Cl- efflux. To address this, the CF pancreatic epithelial cell line CFPAC-1 was infected with increasing doses of AdCFTR, a recombinant Ad containing the normal CFTR cDNA, and analyzed for CFTR mRNA and protein levels and CFTR function. As the AdCFTR dose increased [multiplicity of infection (mail 0-1,000], CFTR mRNA and protein levels increased. However, while CFTR function measured by cAMP-stimulated Cl-36(-) efflux was observed with low doses of the vector (moi 20), there was no further increase in CFTR function with increasing doses of AdCFTR (moi from 20 to 1,000). These data suggest that after AdCFTR-mediated gene transfer, epithelial cells limit the level of cAMP-stimulated Cl- secretion despite increasing levels of CFTR protein. C1 NIH,CTR CLIN,DEPT CLIN PATHOL,SERV HEMATOL,BETHESDA,MD 20892. CORNELL UNIV,COLL MED,DIV PULM & CRIT CARE MED,NEW YORK,NY 10021. RP ROSENFELD, MA (reprint author), NHLBI,PULM BRANCH,ROOM 6D03,BLDG 10,BETHESDA,MD 20892, USA. NR 38 TC 11 Z9 11 U1 0 U2 1 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 SEP PY 1994 VL 5 IS 9 BP 1121 EP 1129 DI 10.1089/hum.1994.5.9-1121 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA PG774 UT WOS:A1994PG77400007 PM 7530494 ER PT J AU IVANOVA, VS ZIMONJIC, D POPESCU, N BONNER, WM AF IVANOVA, VS ZIMONJIC, D POPESCU, N BONNER, WM TI CHROMOSOMAL LOCALIZATION OF THE HUMAN HISTONE H2A.X GENE TO 11Q23.2-Q23.3 BY FLUORESCENCE IN-SITU HYBRIDIZATION SO HUMAN GENETICS LA English DT Note ID HUMAN PORPHOBILINOGEN DEAMINASE; INSITU HYBRIDIZATION; PHOSPHORYLATION; TRANSCRIPTION; TRANSLOCATIONS; INVOLVEMENT; SEQUENCE AB The human histone H2A.X gene is unusual in that its transcripts are alternatively processed to yield two species, one a 0.6-kb replication-linked histone mRNA and the other a 1.6-kb polyadenylated mRNA. The H2A.X gene has been localized by fluorescence in situ hybridization to chromosome 11q23.2-q23.3, away from the known clusters of human histone genes on chromosomes 1, 6, and 12. Assignment to chromosome 11 was substantiated by analysis of human-hamster somatic cell hybrid lines. As this work was being completed, an 89-bps sequence overlap was found between the downstream regions of the H2A.X gene and the recently sequenced hydroxymethylbilane (HMB)-synthase gene. The H2A.X and HMB-synthase genes have an unusual arrangement, being transcribed towards each other with their polyadenylation sites 330 bp apart. In addition the HMB-synthase gene contains constitutive and erythroid specific promoters. K562, an erythroid cell line, was found to contain a high concentration of the 1.6-kb polyadenylated H2A.X mRNA. C1 NCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NCI,BIOL LAB,BETHESDA,MD 20892. NR 20 TC 21 Z9 21 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD SEP PY 1994 VL 94 IS 3 BP 303 EP 306 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA PD329 UT WOS:A1994PD32900017 PM 8076949 ER PT J AU CASTIGLIONI, T MERINO, MJ ELSNER, B LAH, TT SLOANE, BF EMMERTBUCK, MR AF CASTIGLIONI, T MERINO, MJ ELSNER, B LAH, TT SLOANE, BF EMMERTBUCK, MR TI IMMUNOHISTOCHEMICAL ANALYSIS OF CATHEPSIN-D, CATHEPSIN-B, AND CATHEPSIN-L IN HUMAN BREAST-CANCER SO HUMAN PATHOLOGY LA English DT Article DE BREAST CANCER; CATHEPSINS D, B, AND L, PROGNOSIS; IMMUNOHISTOCHEMISTRY ID PROGNOSTIC-SIGNIFICANCE; CARCINOMA; TUMORS AB Cathepsins D, B, and L are acidic lysosomal proteinases involved in intracellular protein turnover. Increased levels of these enzymes have been reported to be indicators of aggressive tumor behavior in human and rodent tumors. In breast cancer increased levels of cathepsin D have been reported to be an independent prognostic factor in women with stage I disease. We used standard immunohistochemical techniques on formalin-fixed, paraffin-embedded tissue to examine the levels of cathepsins D, B, and L in 80 carcinomas of the breast and compared that with other indicators of aggressive tumor behavior, including stage of disease, tumor size, nuclear grade, estrogen receptor status, disease recurrence, and 5-year survival rates. Positive granular cytoplasmic staining was detected for cathepsin D in 90% of the tumors, for cathepsin B in two thirds of the tumors, and for cathepsin L in approximately one half of the tumors. Positive staining also was seen in normal breast epithelium, areas of apocrine metaplasia, stromal fibroblasts, and macrophages. Our results did not show a correlation between the expression of cathepsins D, B, and L and other indicators of aggressive tumor behavior. We conclude that the results obtained using polyclonal anticathepsin antibodies do not support the prognostic usefulness of immunohistochemical analysis of these three proteinases in tumor cells in human breast cancer. HUM PATHOL 25:857-862. This is a US government work. There are no restrictions on its use. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. CTR MED EDUC & CLIN INVEST,BUENOS AIRES,DF,ARGENTINA. ALBERT EINSTEIN MED CTR,DEPT PATHOL,PHILADELPHIA,PA. WAYNE STATE UNIV,SCH MED,DEPT PHARMACOL,DETROIT,MI 48201. RI Sloane, Bonnie/A-1050-2009 FU NCI NIH HHS [CA 36481] NR 27 TC 74 Z9 75 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD SEP PY 1994 VL 25 IS 9 BP 857 EP 862 DI 10.1016/0046-8177(94)90003-5 PG 6 WC Pathology SC Pathology GA PG358 UT WOS:A1994PG35800003 PM 8088759 ER PT J AU BAGROV, AY ANDERSON, DE DMITRIEVA, RI ROUKOYATKINA, NI FRENCH, AW AF BAGROV, AY ANDERSON, DE DMITRIEVA, RI ROUKOYATKINA, NI FRENCH, AW TI ENDOGENOUS BUFODIENOLIDE NA/K-ATPASE INHIBITOR IN PLASMA-VOLUME EXPANSION SO HYPERTENSION LA English DT Meeting Abstract C1 NIA,BALTIMORE,MD. IM SECHENOV EVOLUT PHYSIOL & BIOCHEM INST,ST PETERSBURG,RUSSIA. NR 0 TC 3 Z9 3 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 SEP PY 1994 VL 24 IS 3 BP 407 EP 407 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PG268 UT WOS:A1994PG26800226 ER PT J AU CARSON, RE YAN, YC CHODKOWSKI, B YAP, TK DAUBEWITHERSPOON, ME AF CARSON, RE YAN, YC CHODKOWSKI, B YAP, TK DAUBEWITHERSPOON, ME TI PRECISION AND ACCURACY OF REGIONAL RADIOACTIVITY QUANTITATION USING THE MAXIMUM-LIKELIHOOD EM RECONSTRUCTION ALGORITHM SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article ID POSITRON-EMISSION TOMOGRAPHY; BAYESIAN IMAGE-RECONSTRUCTION; LIKELIHOOD-ESTIMATION; TISSUE HETEROGENEITY; COMPUTED-TOMOGRAPHY; PET SCANNER; NOISE; INFORMATION; PROJECTIONS; CONVERGENCE AB The imaging characteristics of maximum likelihood (ML) reconstruction using the EM algorithm for emission tomography have been extensively evaluated. There has been less study of the precision and accuracy of ML estimates of regional radioactivity concentration. We developed a realistic brain slice simulation by segmenting a normal subject's MRI scan into gray matter, white matter, and CSF and produced PET sinogram data with a model that included detector resolution and efficiencies, attenuation, scatter, and randoms. Noisy realizations at different count levels were created, and ML and filtered backprojection (FBP) reconstructions were performed. The bias and variability of ROI values were determined. In addition, the effects of ML pixel size, image smoothing and region size reduction were assessed. ML estimates at 1000 iterations (0.6 sec per iteration on a parallel computer) for 1-cm2 gray matter ROIs showed negative biases of 6% +/- 2% which can be reduced to 0% +/- 3% by removing the outer 1-mm rim of each ROI. FBP applied to the full-size ROIs had 15% +/- 4% negative bias with 50% less noise than ML. Shrinking the FBP regions provided partial bias compensation with noise increases to levels similar to ML. Smoothing of ML images produced biases comparable to FBP with slightly less noise. Because of its heavy computational requirements, the ML algorithm will be most useful for applications in which achieving minimum bias is important. C1 NIH,CTR CLIN,DEPT NUCL MED,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP CARSON, RE (reprint author), NIH,CTR CLIN,POSITRON EMISS TOMOG,BETHESDA,MD 20892, USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 40 TC 42 Z9 42 U1 4 U2 5 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD SEP PY 1994 VL 13 IS 3 BP 526 EP 537 DI 10.1109/42.310884 PG 12 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA PF414 UT WOS:A1994PF41400012 PM 18218528 ER PT J AU BAKACS, T HADLEY, AG KUMPEL, BM SEGAL, DM BANHIDY, F AF BAKACS, T HADLEY, AG KUMPEL, BM SEGAL, DM BANHIDY, F TI COMPARISON OF THE ABILITY OF RED-CELLS SENSITIZED WITH A BISPECIFIC ANTI-D X ANTI-FC-GAMMA-RIII FAB FRAGMENT TO ACTIVATE HUMAN K-CELLS AND PERITONEAL-MACROPHAGES THROUGH FC-GAMMA-III SO IMMUNOLOGY LETTERS LA English DT Article DE ANTI-D; BISPECIFIC ANTIBODY; FC-GAMMA-RIII; K CELL; MACROPHAGE ID CULTURED HUMAN-MONOCYTES; NATURAL-KILLER CELLS; MONOCLONAL-ANTIBODY; RECEPTOR-III; TARGET-CELL; LYSIS; HETEROGENEITY; ERYTHROCYTES; PHAGOCYTOSIS; BER-MAC3 AB The functional activity of Fc gamma RIII on human K cells from peripheral blood was compared with that of Fc gamma RIII on peritoneal macrophages (PM) separated from the waste material of patients undergoing peritoneal dialysis. Fc gamma R function was assessed in vitro using human monoclonal IgG1 anti-D (AB5) or a bispecific antibody comprising Fab fragments of AB5 chemically linked to Fab fragments of monoclonal anti-Fc gamma RIII, 3G8 (AB5 x 3G8). In antibody-dependent cell-mediated cytotoxicity (ADCC) assays, K cells mediated the lysis of papainized red cells sensitized with the AB5 X 3G8 bispecific antibody but not with AB5. In contrast, red cell lysis by PM was not promoted by AB5 X 3G8 although AB5 was active. However, this lysis, being inhibited by monomeric IgG, was presumably mediated via Fc gamma RI. AB5 X 3G8 also failed to promote the binding and phagocytosis of both papainized and native red cells by PM although 99% of red cells and over 90% of peritoneal-cells bound the bispecific antibody. In marked contrast to K cells therefore, Fc gamma RIII on PM was unable to mediate functional interactions with red cells sensitized with anti-D X anti-Fc-gamma III bispecific antibody. C1 INT BLOOD GRP,REFERENCE LAB,BRISTOL BS10 5ND,AVON,ENGLAND. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RP BAKACS, T (reprint author), NATL INST ONCOL,RATH GYU 7-9,H-1122 BUDAPEST,HUNGARY. NR 27 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD SEP PY 1994 VL 42 IS 1-2 BP 91 EP 95 DI 10.1016/0165-2478(94)90041-8 PG 5 WC Immunology SC Immunology GA PL445 UT WOS:A1994PL44500016 PM 7829136 ER PT J AU KEEGAN, AD NELMS, K WANG, LM PIERCE, JH PAUL, WE AF KEEGAN, AD NELMS, K WANG, LM PIERCE, JH PAUL, WE TI INTERLEUKIN-4 RECEPTOR - SIGNALING MECHANISMS SO IMMUNOLOGY TODAY LA English DT Article ID PROTEIN-TYROSINE PHOSPHORYLATION; DNA-BINDING PROTEINS; T-CELL LINE; GROWTH-FACTOR; HEMATOPOIETIC-CELLS; INSULIN-RECEPTOR; INTERFERON-GAMMA; CYTOKINE RECEPTORS; IL-4 RECEPTOR; LYMPHOCYTES-B AB Achsah Keegan and colleagues consider the signaling mechanisms utilized by the interleukin 4 (IL-4) receptor and review evidence suggesting that these mechanisms cart account for the known responses of hematopoietic and non-hematopoietic cells to IL-4. Most of these data have been obtained from analyses of the ability of IL-4 to regulate the growth of IL-3-dependent myeloid cell lines. These results have implicated a pathway of activation homologous to that utilized by insulin and insulin-like growth factor 1 (IGF-1). However, it is possible that the regulation of growth responses through the IL-4 receptor (and other receptors), and the differentiative events elicited in lymphocytes, may not be mediated by the same post-receptor events. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP KEEGAN, AD (reprint author), NIAID,IMMUNOL LAB,BLDG 10,BETHESDA,MD 20892, USA. NR 58 TC 114 Z9 115 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 SEP PY 1994 VL 15 IS 9 BP 423 EP 432 DI 10.1016/0167-5699(94)90272-0 PG 10 WC Immunology SC Immunology GA PF334 UT WOS:A1994PF33400007 PM 7945783 ER PT J AU KEHRL, JH RIVA, A WILSON, GL THEVENIN, C AF KEHRL, JH RIVA, A WILSON, GL THEVENIN, C TI MOLECULAR MECHANISMS REGULATING CD19, CD20 AND CD22 GENE-EXPRESSION SO IMMUNOLOGY TODAY LA English DT Article ID TRANSCRIPTION FACTOR BSAP; DIFFERENTIATION; PROMOTER; LYMPHOCYTES AB The CD19, CD20 and CD22 genes encode transmembrane proteins that are of vital importance to B-cell function. Similar to the immunoglobulin (Ig) genes, they are expressed in a lineage-specific and developmentally regulated manner. Here, John Kehrl and colleagues describe how an understanding of the transcriptional regulation of the CD19, CD20 and CD22 genes is leading to valuable insights into some of the important molecular events that occur in B-cell development and differentiation. RP KEHRL, JH (reprint author), NIAID,B CELL MOLEC IMMUNOL SECT,IMMUNOREGULAT LAB,BLDG 10,BETHESDA,MD 20892, USA. OI Kehrl, John/0000-0002-6526-159X NR 13 TC 53 Z9 53 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD SEP PY 1994 VL 15 IS 9 BP 432 EP 436 DI 10.1016/0167-5699(94)90273-9 PG 5 WC Immunology SC Immunology GA PF334 UT WOS:A1994PF33400008 PM 7524520 ER PT J AU TAN, TB MARINO, PA PADMANABHAN, R HAMPTON, LL HANLEYHYDE, JM THORGEIRSSON, SS AF TAN, TB MARINO, PA PADMANABHAN, R HAMPTON, LL HANLEYHYDE, JM THORGEIRSSON, SS TI CONSTITUTIVE OVER-EXPRESSION OF TRANSFORMING GROWTH-FACTOR-ALPHA IN RAT-LIVER EPITHELIAL-CELLS LEADS TO INCREASED CELL CYCLING WITHOUT TRANSFORMATION SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE TRANSFORMING GROWTH FACTOR-ALPHA; RAT LIVER EPITHELIAL CELLS; TRANSFORMATION; DIFFERENTIATION ID TGF-ALPHA; MESSENGER-RNA; FACTOR RECEPTORS; TRANSGENIC MICE; EGF-RECEPTOR; V-RAF; LINE; OVEREXPRESSION; FIBROBLASTS; CARCINOMA AB Over-expression of transforming growth factor-alpha (TGF-alpha) is consistently seen in spontaneous transformants of rat liver derived epithelial cells (RLE phi 13) and has been implicated in the transformation of other cultured cells. me have constitutively over-expressed TGF-alpha in RLE phi 13 cells, which are known to express epidermal growth factor receptors, to determine if TGF-alpha over-expression plays a role in transformation or differentiation: or both, of these cells. Early passage RLE phi 13 cells were infected with a replication-defective murine retrovirus that expresses both the full length coding sequence for human TGF-alpha and the neomycin-resistance gene. Integration of the transcriptionally active provirus and expression of TGF-alpha mRNA were confirmed. Neither morphologic transformation nor molecular evidence for differentiation was noted in TGF-alpha-producing clones. However, these clones did exhibit an accelerated growth rate, increased expression of several cell cycle related genes including mitotic cyclic B-1, proliferating cell nuclear antigen, c-myc, and p53 as well as increased expression of the preneoplastic marker enzyme, glutathione-S-transferase. This suggests that over-expression of TGF-alpha results in increased cell cycling, and that subsequent events must be necessary for cellular transformation or differentiation or both. C1 NCI,DIV CANC ETIOL,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,DIV CANC BIOL DIAG & CTR,GENET LAB,INTRAMURAL RES PROGRAM,BETHESDA,MD 20892. NR 70 TC 5 Z9 5 U1 0 U2 1 PU SOC IN VITRO BIOLOGY PI UPPER MARLBORO PA 9315 LARGO DR W #255, UPPER MARLBORO, MD 20774-4755 SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD SEP PY 1994 VL 30A IS 9 BP 615 EP 621 PG 7 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA PG049 UT WOS:A1994PG04900012 PM 7820313 ER PT J AU BEATTY, WL BELANGER, TA DESAI, AA MORRISON, RP BYRNE, GI AF BEATTY, WL BELANGER, TA DESAI, AA MORRISON, RP BYRNE, GI TI TRYPTOPHAN DEPLETION AS A MECHANISM OF GAMMA-INTERFERON-MEDIATED CHLAMYDIAL PERSISTENCE SO INFECTION AND IMMUNITY LA English DT Article ID OUTER-MEMBRANE PROTEIN; INDOLEAMINE 2,3-DIOXYGENASE ACTIVITY; ANTI-MICROBIAL ACTIVITY; NUCLEOTIDE-SEQUENCE; INTRACELLULAR CHLAMYDIA; MACROPHAGE ACTIVATION; MONOCLONAL-ANTIBODIES; PSITTACI REPLICATION; OXIDATIVE-METABOLISM; HOST-CELLS AB Previous studies have shown that the immune-regulated cytokine gamma interferon (IFN-gamma) activates host cells to restrict intracellular growth of the bacterial pathogen Chlamydia trachomatis by induction of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO). Recently, subinhibitory levels of IFN-gamma were used to generate an in vitro persistent chlamydial infection characterized by large aberrant, noninfectious reticulate bodies from which infectious progeny could be recovered following the removal of IFN-gamma. Studies were done to determine if the mechanism functioning to induce chlamydiae to enter a persistent state in the presence of low levels of IFN-gamma was similar to that reported to inhibit chlamydial growth. Host cells treated with levels of IFN-gamma required to induce persistence were assessed for IDO activity by high-performance liquid chromatography analysis of tryptophan and its catabolic products. Substantial tryptophan catabolism was detected in acid-soluble cellular pools, indicating that the intracellular availability of this essential amino acid was limited under these conditions. In addition, a mutant cell line responsive to IFN-gamma but deficient in IDO activity was Shown to support C trachomatis growth, but aberrant organisms were not induced in response to IFN-gamma treatment. Analyses of infected cells cultured in medium with incremental levels of exogenous tryptophan indicated that persistent growth was induced by reducing the amount of this essential amino acid. These studies confirmed that nutrient deprivation by IDO-mediated tryptophan catabolism was the mechanism by which IFN-gamma mediates persistent growth of C. trachomatis. C1 UNIV WISCONSIN,DEPT MED MICROBIOL & IMMUNOL,MADISON,WI 53706. NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,HAMILTON,MT 59840. FU NIAID NIH HHS [R01 AI019782, AI 19782, AI 34617] NR 40 TC 188 Z9 190 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 1994 VL 62 IS 9 BP 3705 EP 3711 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA PC836 UT WOS:A1994PC83600015 PM 8063385 ER PT J AU JONES, BD FALKOW, S AF JONES, BD FALKOW, S TI IDENTIFICATION AND CHARACTERIZATION OF A SALMONELLA-TYPHIMURIUM OXYGEN-REGULATED GENE REQUIRED FOR BACTERIAL INTERNALIZATION SO INFECTION AND IMMUNITY LA English DT Article ID CULTURED EPITHELIAL-CELLS; MOLECULAR CHARACTERIZATION; HELA-CELLS; TETRACYCLINE RESISTANCE; SHIGELLA-FLEXNERI; INVASION; CLONING; GROWTH; ANAEROBIOSIS; PENETRATION AB Growth of Salmonella typhimurium in a low-oxygen environment induces the ability of these bacteria to enter mammalian cells. We have carried out a search for invasion genes that are expressed under low-oxygen conditions by using Tn51acZY transcriptional fusions. Several noninvasive oxygen-regulated lacZY insertion strains have been identified. The invasion defect in one of these noninvasive S. typhimurium strains, BJ66, has been complemented by introduction of a cosmid (pBDJ125) from an S. typhimurium SL1344 gene bank G 1.9-kb EcoRV DNA fragment subcloned from this cosmid, containing a single open reading frame (orgA), restores the ability of BJ66 to invade mammalian cells. Comparative searches of the GenBank and EMBL sequence data banks with the nucleotide sequence of the gene and deduced amino acid sequence of the protein reveal no significant similarities. Interestingly, hybridization of an orgA gene probe with a P22 chromosomal mapping library demonstrated that the orgA gene maps to a region on the chromosome between 57.5 and 60 min where other Salmonella invasion genes have been mapped. Other enteroinvasive bacteria (shigella flexneri, Escherichia coli, Yersinia spp., and Listeria monocytogenes) lack sequences which cross hybridize to the probe. We have compared the virulence of S. typhimurium SL1344 and an isogenic orgA mutant in a mouse model of typhoid fever. The orgA mutant was as virulent as the wild-type strain was when inoculated intraperitoneally but is significantly reduced (>60-fold) in its ability to cause disease by an oral route of infection. C1 STANFORD UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. NIH,ROCKY MT LAB,MICROSCOPY BRANCH,HAMILTON,MT 59840. FU NIAID NIH HHS [AI08404, AI26195]; NIDDK NIH HHS [DK38707] NR 49 TC 133 Z9 138 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 1994 VL 62 IS 9 BP 3745 EP 3752 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA PC836 UT WOS:A1994PC83600020 PM 8063389 ER PT J AU BEATTY, WL MORRISON, RP BYRNE, GI AF BEATTY, WL MORRISON, RP BYRNE, GI TI IMMUNOELECTRONMICROSCOPIC QUANTITATION OF DIFFERENTIAL LEVELS OF CHLAMYDIAL PROTEINS IN A CELL-CULTURE MODEL OF PERSISTENT CHLAMYDIA-TRACHOMATIS INFECTION SO INFECTION AND IMMUNITY LA English DT Note ID OUTER-MEMBRANE PROTEIN; PROTECTIVE MONOCLONAL-ANTIBODIES; INTERFERON-GAMMA; PURIFICATION; EPITOPES AB Electron immunolabeling techniques were used for quantitative evaluation of alterations in the steady-state levels of chlamydial antigens in persistent Chlamydia trachomatis cultures. Gamma interferon-mediated persistent chlamydial development correlated with an increase in the levels of the chlamydial heat shock protein (hsp60) and with a significant reduction in the levels of the major outer membrane protein. C1 UNIV WISCONSIN,DEPT MED MICROBIOL & IMMUNOL,MADISON,WI 53706. NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,HAMILTON,MT 59840. FU NIAID NIH HHS [AI 19782, AI 34617, R01 AI019782, P01 AI034617] NR 11 TC 43 Z9 43 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 1994 VL 62 IS 9 BP 4059 EP 4062 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA PC836 UT WOS:A1994PC83600062 PM 7914884 ER PT J AU SHORES, EW VANEWIJK, W SINGER, A AF SHORES, EW VANEWIJK, W SINGER, A TI MATURATION OF MEDULLARY THYMIC EPITHELIUM REQUIRES THYMOCYTES EXPRESSING FULLY ASSEMBLED CD3-TCR COMPLEXES SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE INDUCTION; MOUSE; TCR TRANSGENIC ANIMAL; THYMIC EPITHELIUM ID RECEPTOR-BETA-CHAIN; STROMAL CELL-TYPES; MONOCLONAL-ANTIBODIES; T-CELLS; SCID MICE; ANTIGEN RECEPTOR; TRANSGENIC MICE; GAMMA-CHAIN; MOUSE; DIFFERENTIATION AB Unlike medullary thymic epithelial cells (TEC) of normal mice, medullary TEC of TCR(-) SCID mice are immature and disorganized. In order to assess directly the role of TCR(+) cells in the development of medullary TEC, we bred mice which co-expressed the SCID genetic defect and transgenes encoding clonotypic TCR chains. Immunohistologic examination revealed that medullary thymic epithelial cells from TCR beta transgenic SCID mice, whose thymocytes only express TCR beta chains that inefficiently associate with CD3 and zeta components, remained immature and disorganized. In contrast, medullary TEC from TCR alpha beta transgenic solo mice, whose thymocytes express fully assembled CD3-zeta-TCR alpha beta complexes were mature and organized. Interestingly, the ability of TCR alpha beta(+)-zeta(+)-CD3(+) thymocytes to induce maturation of medullary TEC appeared not to be related to the antigen specificity of the TCR as thymi from positively selecting, negatively selecting and non-selecting TCR alpha beta transgenic SCID mice all possessed induced medullary thymic epithelial cells. In addition, we found that induction of medullary TEC cells was associated with the presence of medullary thymocytes, including those of the CD4(-)CD8(-) TCR alpha beta(+) phenotype. The present findings demonstrate that fully assembled CD3-zeta-TCR complexes are required to induce maturation of medullary thymic epithelial cells and indicate that thymocyte induction of medullary thymic epithelial cells may result from signaling independently of their clonotypic TCR chains. C1 ERASMUS UNIV ROTTERDAM,DEPT IMMUNOL,3000 DR ROTTERDAM,NETHERLANDS. RP SHORES, EW (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B17,BETHESDA,MD 20892, USA. NR 43 TC 61 Z9 62 U1 1 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD SEP PY 1994 VL 6 IS 9 BP 1393 EP 1402 DI 10.1093/intimm/6.9.1393 PG 10 WC Immunology SC Immunology GA PK413 UT WOS:A1994PK41300012 PM 7819148 ER PT J AU JENSEN, SM JONES, JE PASS, H STEINBERG, SM LINNOILA, RI AF JENSEN, SM JONES, JE PASS, H STEINBERG, SM LINNOILA, RI TI CLARA CELL 10-KDA PROTEIN MESSENGER-RNA IN NORMAL AND ATYPICAL REGIONS OF HUMAN RESPIRATORY EPITHELIUM SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID LUNG; EXPRESSION; CANCER AB We used RNA-RNA in situ hybridization to study expression of the human CC 10 gene in morphologically normal and atypical areas of 32 non-neoplastic lung specimens resected from 26 non-small cell lung cancer patients. We scored strong, moderate or weak levels of CC 10 mRNA expression in 3 distinct lung compartments. In morphologically normal lungs, strong and moderate levels of CC10 mRNA were observed in bronchioli and bronchi, respectively, but the expression was rarely observed in the alveolar region. Distinct alterations in CC10 mRNA expression were noted in specific histologic abnormalities within bronchi and the alveolar region. CC10 hybridization signal decreased markedly in bronchi containing diffuse goblet cell hyperplasia or squamous metaplasia, while CC10 mRNA expression remained unchanged in bronchi with basal cell hyperplasia or focal goblet cell hyperplasia. Bronchiolar CC10 mRNA levels remained unchanged in sections containing abnormalities elsewhere. Interestingly, in alveoli with bronchiolization of the alveoli, high levels of CC10 mRNA were observed. These regions also contained strongly stained keratin 14-positive cells, which may indicate a concurrent metaplastic process. In lungs with morphologic atypias, no correlation was found between abnormalities detected in bronchi and alveoli from the same lung. A comparison of mRNA expression and clinicopathologic features demonstrated that the amount of histologic abnormalities increased with smoking history (pack years); however, no correlation between CC10 mRNA expression and sex, age or smoking history was found. (C) 1994 Wiley-Liss, Inc. C1 NCI,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD 20850. NCI,SURG BRANCH,BETHESDA,MD 20852. NCI,CLIN ONCOL PROGRAM,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20852. NR 25 TC 32 Z9 32 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 1 PY 1994 VL 58 IS 5 BP 629 EP 637 DI 10.1002/ijc.2910580503 PG 9 WC Oncology SC Oncology GA PE112 UT WOS:A1994PE11200002 PM 7521325 ER PT J AU DEBINSKI, W PURI, RK PASTAN, I AF DEBINSKI, W PURI, RK PASTAN, I TI INTERLEUKIN-4 RECEPTORS EXPRESSED ON TUMOR-CELLS MAY SERVE AS A TARGET FOR ANTICANCER THERAPY USING CHIMERIC PSEUDOMONAS EXOTOXIN SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID GROWTH-FACTOR-ALPHA; ANTITUMOR-ACTIVITY; TOXIN; IMMUNOTOXINS; CARCINOMA; MICE AB Interleukin-4 receptors (IL4R) are present on a wide variety of human cancer cells derived from both hematopoietic and epithelial malignancies. We have targeted IL4R on a human solid tumor xenograft with chimeric proteins composed of human IL4 (hIL4) and 2 different mutant forms of a powerful bacterial toxin, Pseudomonas exotoxin A (PE). The 2 chimeric toxins, termed hIL4-PE(4E) and hlL4-PE38QQR, showed specific, hIL4R-dependent and dose-dependent antitumor activities. Neither of the chimeric toxins showed antitumor potency when the ADP-ribosylation activity of the toxin was inactivated by mutagenesis. One of the chimeras, hIL4-PE38QQR, caused a complete although transient regression of established solid tumors. These observations indicate that hIL4-PE chimeric proteins should be further evaluated for the treatment of human malignancies. (C) 1994 Wiley-Liss, Inc. C1 UNIV MONTREAL,HOTEL DIEU HOSP,RES CTR,MOLEC TARGETING LAB,MONTREAL H2W 1T8,PQ,CANADA. US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,MOLEC TUMOR BIOL LAB,BETHESDA,MD 20892. NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 20 TC 23 Z9 24 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 1 PY 1994 VL 58 IS 5 BP 744 EP 748 DI 10.1002/ijc.2910580520 PG 5 WC Oncology SC Oncology GA PE112 UT WOS:A1994PE11200019 PM 8077061 ER PT J AU YAMADA, S YAMADA, KM BROWN, KE AF YAMADA, S YAMADA, KM BROWN, KE TI INTEGRIN REGULATORY SWITCHING IN DEVELOPMENT - OSCILLATION OF BETA(5) INTEGRIN MESSENGER-RNA EXPRESSION DURING EPITHELIAL-MESENCHYMAL INTERACTIONS IN TOOTH DEVELOPMENT SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Note DE INTEGRIN; TOOTH DEVELOPMENT; MOUSE EMBRYOS; IN SITU HYBRIDIZATION ID CELL-ADHESION MOLECULES; INSITU HYBRIDIZATION; RNA; FIBRONECTIN; RECEPTOR; EMBRYOS; DIFFERENTIATION; MORPHOGENESIS; COLLAGEN; SUBUNIT AB Integrin receptors for extracellular matrix molecules are thought to play important roles in morphogenesis since they mediate aspects of embryonic cell adhesion and migration. Using in situ hybridization, the mRNA expression pattern of the beta(5), integrin receptor subunit was examined during murine tooth development, a classical system for studying morphogenesis. In developing tooth, high-level expression of beta(5), integrin mRNA alternates from epithelium to mesenchyme and back to epithelium. Each switch in localization occurs within one day. These results demonstrate that an integrin mRNA can be precisely and rapidly up- and down-regulated over unexpectedly short time spans, and that expression can oscillate between adjacent, interacting epithelial and mesenchymal tissues during morphogenesis. This rapid modulation of mRNA expression suggests a potential regulatory role for the beta(5) integrin receptor in morphogenesis. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NR 25 TC 13 Z9 13 U1 0 U2 0 PU UNIV BASQUE COUNTRY PRESS PI BILBAO PA POST BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PD SEP PY 1994 VL 38 IS 3 BP 553 EP 556 PG 4 WC Developmental Biology SC Developmental Biology GA PK969 UT WOS:A1994PK96900018 PM 7848840 ER PT J AU OPPENHEIM, JJ LLOYD, A TAUB, D WANG, JM MURPHY, B AF OPPENHEIM, JJ LLOYD, A TAUB, D WANG, JM MURPHY, B TI ATTRACTIVE PROPERTIES OF CHEMOKINES AND THEIR RECEPTORS SO INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT International Meeting on Cytokines, AIDS and Immunity CY FEB 28, 1994 CL CHIETI, ITALY ID FUNCTIONAL EXPRESSION AB Chemokines are small proteins inducible in a number of pathophysiological processes. IL-8 binds polymorphonuclear neutrophils and resulted to be chemoattractant for these cells. Here J.J. Oppenheim, et. al. shed light on IL-8 and a number of other chemoattractive cytokines that have been identified over the past 8 years on their attractive properties and their receptors. This mini review is a summary of the lecture presented at the Meeting on Cytokines, AIDS, and Immunity held on February 28, 1994 at the University of Chieti, Chieti, Italy, RP OPPENHEIM, JJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,IMMUNOREG LAB,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702, USA. NR 6 TC 23 Z9 23 U1 0 U2 0 PU BIOMEDICAL RESEARCH PRESS, SAS PI CHIETI PA PROF PIO CONTI, EDITOR DEPT IMMUNOLOGY, UNIV CHIETI VIA VESTINI, 66100 CHIETI, ITALY SN 0394-6320 J9 INT J IMMUNOPATH PH JI Int. J. Immunopathol. Pharmacol. PD SEP-DEC PY 1994 VL 7 IS 3 BP 219 EP 220 PG 2 WC Immunology; Pathology; Pharmacology & Pharmacy SC Immunology; Pathology; Pharmacology & Pharmacy GA PZ973 UT WOS:A1994PZ97300007 ER PT J AU SAEKI, T SALOMON, DS GULLICK, WJ MANDAI, K YAMAGAMI, K MORIWAKI, S TAKASHIMA, S NISHIKAWA, Y TAHARA, E AF SAEKI, T SALOMON, DS GULLICK, WJ MANDAI, K YAMAGAMI, K MORIWAKI, S TAKASHIMA, S NISHIKAWA, Y TAHARA, E TI EXPRESSION OF CRIPTO-1 IN HUMAN COLORECTAL ADENOMAS AND CARCINOMAS IS RELATED TO THE DEGREE OF DYSPLASIA SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE CRIPTO-1; EGFR; P53; COLONIC NEOPLASM ID HUMAN-COLON CARCINOMA; GROWTH-FACTOR; CELL-LINES; TGF-ALPHA; GENE; TUMORS; FAMILY; AMPHIREGULIN; CANCER AB The expression and localization of cripto-1 (CR-1) and epidermal growth factor receptor (EGFR) were assessed by immunocytochemistry in 41 human colorectal carcinomas, 57 adenomas, 9 hyperplastic polyps and in 98 noninvolved colonic mucosa samples that were adjacent to adenoma and/or carcinoma. Thirty-two (78.0%) and 19 (46%) carcinomas showed staining for CR-1 and EGFR, respectively, whereas 24 (42.0%) and 25 (43.8%) of the adenoma samples were reactive with the anti-CR-1 and anti-EGER antibodies, respectively. Two (22.2%) and 1 (11.1%) of the hyperplastic polyps demonstrated moderate levels of staining with anti-CR-1 and anti-EGFR antibodies. In contrast, none of the normal, noninvolved colonic mucosa samples reacted with the CR-1 antibody, whereas only 1 (1.0%) reacted with the EGFR antibody. Between EGFR and CR-1 expression, there was no significant association within either adenomas or carcinomas. A significant difference in the incidence for CR-1 expression was observed between adenomas and carcinomas (p<0.001). Within adenomas, the frequency of CR-1 was related to the histological degree of atypia. Immunostaining for p53 was also observed in 10 (24%) of the carcinomas, in 10 (17%) of the adenomas and in none of the hyperplastic polyps nor colonic mucosa samples. No statistically significant difference for p53 staining was observed between the adenomas and carcinomas. However, adenomas with moderate atypia exhibited relatively strong positive staining for p53 (p<0.05) compared to either adenomas with mild or severe atypia. A slight trend (p<0.05) for coexpression of p53 and CR-1 was detected in adenomas but not in carcinomas. These data demonstrate that CR-1 is a tumor marker for colon carcinomas and additionally that the expression of CR-1 may be an important factor in the early stages of colon cancer development during the adenomacarcinoma transition. C1 NATL SHIKOKU CANC CTR HOSP,DEPT CLIN RES PATHOL SURG & INTERNAL MED,MATSUYAMA,EHIME,JAPAN. NCI,TUMOR IMMUNOL & BIOL LAB,TUMOR GROWTH FACTOR SECT,BETHESDA,MD. HAMMERSMITH HOSP,IMPERIAL CANC RES FUND,MOLEC ONCOL UNIT,LONDON W12 0HS,ENGLAND. HIROSHIMA UNIV,SCH MED,DEPT PATHOL,HIROSHIMA,JAPAN. NR 32 TC 12 Z9 12 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD SEP PY 1994 VL 5 IS 3 BP 445 EP 451 PG 7 WC Oncology SC Oncology GA PD796 UT WOS:A1994PD79600002 PM 21559596 ER PT J AU MILTON, RC AF MILTON, RC TI STATISTICAL-METHODS FOR BINARY OUTCOMES SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Letter RP MILTON, RC (reprint author), NEI,BETHESDA,MD 20892, USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 1994 VL 35 IS 10 BP 3573 EP 3573 PG 1 WC Ophthalmology SC Ophthalmology GA PH607 UT WOS:A1994PH60700001 PM 8088947 ER PT J AU PUTNAM, FW AF PUTNAM, FW TI A SKEPTICAL REFLECTION ON THE DIAGNOSIS OF MULTIPLE PERSONALITY-DISORDER - COMMENTARY SO IRISH JOURNAL OF PSYCHOLOGICAL MEDICINE LA English DT Note ID DISSOCIATIVE DISORDERS; PSYCHIATRIC-INPATIENTS RP PUTNAM, FW (reprint author), NIMH,DEV PSYCHOL LAB,DISSOCIAT DISORDERS UNIT,BETHESDA,MD 20892, USA. NR 17 TC 1 Z9 1 U1 1 U2 2 PU IRISH INST PSYCHOLOGICAL MEDICINE LTD PI DUBLIN 7 PA IRISH J PSYCHOL MEDICINE, BRENDANS HOSPITAL, RATHDOWN RD, DUBLIN 7, IRELAND SN 0790-9667 J9 IRISH J PSYCHOL MED JI Irish J. Psychol. Med. PD SEP PY 1994 VL 11 IS 3 BP 130 EP 131 PG 2 WC Psychology; Psychology, Multidisciplinary SC Psychology GA PL952 UT WOS:A1994PL95200008 ER PT J AU COOKDEGAN, R FREDRICKSON, DS JOSEPH, SC RALL, DP FINNERAN, K AF COOKDEGAN, R FREDRICKSON, DS JOSEPH, SC RALL, DP FINNERAN, K TI MEDICINE, PUBLIC-HEALTH, AND ENVIRONMENT SO ISSUES IN SCIENCE AND TECHNOLOGY LA English DT Discussion C1 NATL LIB MED,BETHESDA,MD 20209. NATL RES COUNCIL,BOARD ENVIRONM STUDIES & TOXICOL,WASHINGTON,DC 20418. RP COOKDEGAN, R (reprint author), INST MED,DIV BIOBEHAV SCI & MENTAL DISORDERS,WASHINGTON,DC, USA. OI Cook-Deegan, Robert/0000-0002-8251-4237 NR 3 TC 0 Z9 0 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0748-5492 J9 ISSUES SCI TECHNOL JI Issues Sci. Technol. PD FAL PY 1994 VL 11 IS 1 BP 68 EP 74 PG 7 WC Engineering, Multidisciplinary; Engineering, Industrial; Multidisciplinary Sciences; Social Issues SC Engineering; Science & Technology - Other Topics; Social Issues GA PL710 UT WOS:A1994PL71000028 PM 10154972 ER PT J AU LARSON, DE HESSLINK, RL HROVAT, MI FISHMAN, RS SYSTROM, DM AF LARSON, DE HESSLINK, RL HROVAT, MI FISHMAN, RS SYSTROM, DM TI DIETARY-EFFECTS ON EXERCISING MUSCLE METABOLISM AND PERFORMANCE BY P-31-MRS SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE GLYCOLYSIS; PHOSPHATE SPECTROSCOPY; PHOSPHOCREATINE; VENTILATION; SKELETAL MUSCLE ID MAGNETIC-RESONANCE SPECTROSCOPY; BLOOD LACTATE ACCUMULATION; HIGH-FAT DIET; PROLONGED EXERCISE; INCREMENTAL EXERCISE; ANAEROBIC THRESHOLD; GLYCOGEN DEPLETION; SKELETAL-MUSCLE; FATIGUE; INHIBITION AB To determine how diet modulates short-term exercise capacity, skeletal muscle pH and bioenergetic state were examined by P-31-magnetic resonance spectroscopy in nine healthy volunteers. Subjects performed incremental quadriceps exercise to exhaustion after 5 days of high-carbohydrate (HCHO) or high-fat (HFAT) diet randomly assigned in crossover fashion and separated by a 2.5-day period of ad libitum mixed diet. Simultaneous measurements were made of pulmonary gas exchange, minute ventilation, and quadriceps muscle pH and phosphorylation potential. At rest and peak exercise, respiratory exchange ratio and minute ventilation were higher after HCHO than after HFAT (P < 0.05), reflecting greater CHO utilization. Peak O-2 consumption VO2) was not increased after HCHO (P > 0.05), but exercise duration was (339 +/- 34 s for HCHO vs. 308 +/- 25 s for HFAT; P < 0.05). HCHO was associated with a blunted early fall of phosphocreatine (PCr)/P-i vs. VO2 (-4.1 +/- 0.7 x 10(-2) min/ml for HCHO vs. -5.6 +/- 1.2 X 10(-2) min/ml for HFAT; P < 0.05). On both study days, the slope of PCr/P-i vs. VO2, before and after the PCr threshold, was correlated with exercise time. The results suggest that a diet rich in CHO improves exercise efficiency through beneficial effects on intracellular phosphorylation potential. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MASSACHUSETTS INST TECHNOL,BOSTON,MA 02114. NIDDKD,CLIN DIABET & NUTR SECT,PHOENIX,AZ 85016. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MASSACHUSETTS INST TECHNOL,BOSTON,MA 02114. USN,HLTH RES CTR,SAN DIEGO,CA 92128. FU NHLBI NIH HHS [HL-07354-14, K08-HL-02593-01A2] NR 39 TC 20 Z9 20 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD SEP PY 1994 VL 77 IS 3 BP 1108 EP 1115 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA PG916 UT WOS:A1994PG91600010 PM 7836111 ER PT J AU FLEG, JL SCHULMAN, SP OCONNOR, FC GERSTENBLITH, G BECKER, LC FORTNEY, S GOLDBERG, AP LAKATTA, EG AF FLEG, JL SCHULMAN, SP OCONNOR, FC GERSTENBLITH, G BECKER, LC FORTNEY, S GOLDBERG, AP LAKATTA, EG TI CARDIOVASCULAR-RESPONSES TO EXHAUSTIVE UPRIGHT CYCLE EXERCISE IN HIGHLY TRAINED OLDER MEN SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE OXYGEN CONSUMPTION; OLDER ATHLETES; CARDIAC OUTPUT; ARTERIOVENOUS OXYGEN DIFFERENCE ID LEFT-VENTRICULAR VOLUME; YOUNG; ADAPTATIONS; WOMEN; DECLINE; MUSCLE; VO2MAX; AGE AB It is unclear whether the markedly enhanced aerobic exercise capacity of older endurance-trained men relative to their sedentary age peers is mediated primarily by central or peripheral cardiovascular mechanisms. To address this question, we performed radionuclide ventriculography with respiratory gas exchange measurements during exhaustive upright cycle ergometry in 16 endurance-trained men aged 63 +/- 7 yr and in 35 untrained men of similar age. As expected, maximal O-2 consumption during treadmill exercise was much higher in athletes than in controls. At rest and during fixed submaximal cycle work rates through 100 W, athletes demonstrated lower heart rates and greater stroke volume indexes than controls while maintaining similar cardiac indexes and O-2 uptake (Vo(2)). At exhaustion, athletes achieved 53% higher work rates and peak Vo(2) per kilogram body weight than the sedentary men. The higher peak Vo(2) in athletes was achieved by a 22.5% larger cardiac index and a 15.6% greater arteriovenous O-2 difference. The larger peak cardiac index in the athletes than in sedentary controls was mediated entirely by a greater stroke volume index; peak heart rates were virtually identical. The athletes' greater stroke volume index was achieved through an 11% larger end-diastolic volume index and a 7% higher ejection fraction, both of borderline significance. At exhaustion, athletes demonstrated a lower systemic vascular resistance than controls, despite a higher value at rest. Athletes also showed greater exercise-induced increments in heart rate, stroke volume index, and cardiac index and a greater reduction in systemic vascular resistance from rest to maximal workload. Thus the higher aerobic capacity in endurance-trained older men during exhaustive upright cycle ergometry than in their sedentary age peers is achieved through central and peripheral mechanisms, which are of similar magnitude. C1 JOHNS HOPKINS MED INST,DIV CARDIOL,BALTIMORE,MD 21205. JOHNS HOPKINS MED INST,DEPT ENVIRONM PHYSIOL,BALTIMORE,MD 21205. UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,BALTIMORE,MD 21218. RP FLEG, JL (reprint author), NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. FU NIA NIH HHS [N01-AG-4-2109, P01-AG-04402-9, R01-AG-07660] NR 33 TC 29 Z9 29 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD SEP PY 1994 VL 77 IS 3 BP 1500 EP 1506 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA PG916 UT WOS:A1994PG91600060 PM 7836158 ER PT J AU WONG, KK WONG, RM RUDD, KE MCCLELLAND, M AF WONG, KK WONG, RM RUDD, KE MCCLELLAND, M TI HIGH-RESOLUTION RESTRICTION MAP FOR A 240-KILOBASE REGION SPANNING 91 TO 96 MINUTES ON THE SALMONELLA-TYPHIMURIUM LT2 CHROMOSOME SO JOURNAL OF BACTERIOLOGY LA English DT Article ID PHYSICAL MAP; GENOME; SEQUENCE AB A hierarchical approach allows the completion of contiguous sets of overlapping clones for small regions of a genome, one at a time rather than tackling the whole genome at once. On the basis of the BlnI restriction map for Salmonella typhimurium LT2, we dissected the chromosome into 21 different fragments by using a Tn5 transposon carrying a BlnI site. Dissected chromosomal fragments were purified by pulsed-field gel electrophoresis and used as probes for sorting a lambda DASHII genomic library of 2,304 primary clones. A total of 129 clones identified as spanning the region from 91 min to 98 min were partly ordered on the basis of the intensity of hybridization with mitomycin-induced Mud-P22 phage DNAs from insertions with pac sites in opposite orientations at 93 min used as probes. Decreased signal intensity with the Mud-P22 probes corresponded to the increased distance of the clone from the site of Mud-P22 insertion and allowed the clones to be placed in two groups from 91 min to 93 min and from 93 min to 98 min and into four intensity categories within the two groups. A member of each category was used to generate a riboprobe from the T3 promoter flanking the insert. This probe identified overlapping clones among the 129 clones. This subchromosomal library was then screened again with riboprobes from nonoverlapping clones. After four cycles of this strategy, a minimal contiguous sequence of 19 partly overlapping clones was selected for restriction mapping. A detailed map of 378 sites for eight restriction enzymes is presented for a region of about 240 kb. Working clockwise, the following genes were placed on this physical map on the basis of their restriction maps: malFEK, lamB, malM, lexA, qor, dnaB, air, uvrA, proP, pmrB, pmrA, melA, melB, phoN, amiB, mutL, and miaA. C1 CALIF INST BIOL RES,LA JOLLA,CA 92037. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. RI McClelland, Michael/A-8583-2011; OI Wong, Kwong-Kwok/0000-0002-0375-6669; McClelland, Michael/0000-0003-1788-9347 FU NHGRI NIH HHS [HG00456]; NIAID NIH HHS [AI32644, AI34829] NR 17 TC 5 Z9 5 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 SEP PY 1994 VL 176 IS 18 BP 5729 EP 5734 PG 6 WC Microbiology SC Microbiology GA PF222 UT WOS:A1994PF22200018 PM 8083165 ER PT J AU MARCUS, R GREENDALE, G BLUNT, BA BUSH, TL SHERMAN, S SHERWIN, R WAHNER, H WELLS, B AF MARCUS, R GREENDALE, G BLUNT, BA BUSH, TL SHERMAN, S SHERWIN, R WAHNER, H WELLS, B TI CORRELATES OF BONE-MINERAL DENSITY IN THE POSTMENOPAUSAL ESTROGEN/PROGESTIN INTERVENTIONS TRIAL SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID DUAL-PHOTON-ABSORPTIOMETRY; X-RAY ABSORPTIOMETRY; HIP FRACTURE; BODY-COMPOSITION; MUSCLE STRENGTH; LUMBAR SPINE; FEMORAL-NECK; WOMEN; MASS; AGE AB We assessed the cross-sectional relationship of age, menopausal years, body mass, previous estrogen use, and ethnic background to bone mineral status in a sample of 875 healthy postmenopausal women at the time they were recruited from the community to participate in a multicenter clinical trial. The women were 1-10 years postmenopause, 45-64 years of age, and had not received estrogen replacement therapy within 3 months of enrollment. Of the participants, 89% were white, 69% had a spontaneous menopause, and 53% had a history of previous estrogen replacement therapy. Bone mineral density (BMD) of the lumbar spine (L2-4) and proximal femur was measured by dual-energy x-ray absorptiometry, Results were consistent with a significant negative linear regression of BMD on age or years from menopause. Body mass index (BMI) correlated significantly with BMD at all sites (L 2-4 r = 0.28; femoral neck r = 0.34, p < 0.0001). BMD adjusted for age and BMI were higher at both sites in women who had taken estrogen versus those who had not (L2-4 0.976 +/- 0.009 versus 0.932 +/- 0.01; femoral neck 0.740 +/- 0.006 versus 0.708 +/- 0.008, p < 0.05). Adjusted BMD also increased with duration of ERT. Parity was negatively associated with L2-4 BMD (p = 0.03) but did not correlate significantly with BMD at the femoral neck. Black women had the highest L2-4 BMD, and Hispanic women had the highest femoral neck BMD, even when results were adjusted for age and BMI. When data were corrected for differences in bone size, these interethnic differences were no longer significant. We conclude that increased body mass is positively correlated with BMD, and this may confer a degree of skeletal protection to heavier postmenopausal women. Exposure for 5 years to exogenous estrogen is associated with significantly increased age- and BMI-adjusted BMD. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT OBSTET & GYNECOL,LOS ANGELES,CA 90024. UNIV CALIF SAN DIEGO,DEPT COMMUNITY & FAMILY MED,LA JOLLA,CA 92093. JOHNS HOPKINS UNIV,DEPT EPIDEMIOL,BALTIMORE,MD. NIA,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,DEPT EPIDEMIOL & PREVENT MED,BALTIMORE,MD 21201. MAYO CLIN & MAYO FDN,DEPT DIAGNOST RADIOL,ROCHESTER,MN 55905. BOWMAN GRAY SCH MED,PEPI COORDINAT CTR,DEPT PUBL HLTH SCI,WINSTON SALEM,NC. RP MARCUS, R (reprint author), STANFORD UNIV,DEPT VET AFFAIRS MED CTR,GRECC 182B,DEPT MED,AGING STUDY UNIT,3801 MIRANDA AVE,PALO ALTO,CA 94304, USA. FU NHLBI NIH HHS [UO1-HL40154, UO1-HL40185, UO1-HL40195] NR 41 TC 77 Z9 77 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 1994 VL 9 IS 9 BP 1467 EP 1476 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PD706 UT WOS:A1994PD70600019 PM 7817832 ER PT J AU BOSSHART, H HUMPHREY, J DEIGNAN, E DAVIDSON, J DRAZBA, J YUAN, L OORSCHOT, V PETERS, PJ BONIFACINO, JS AF BOSSHART, H HUMPHREY, J DEIGNAN, E DAVIDSON, J DRAZBA, J YUAN, L OORSCHOT, V PETERS, PJ BONIFACINO, JS TI THE CYTOPLASMIC DOMAIN MEDIATES LOCALIZATION OF FURIN TO THE TRANS-GOLGI NETWORK EN-ROUTE TO THE ENDOSOMAL LYSOSOMAL SYSTEM SO JOURNAL OF CELL BIOLOGY LA English DT Article ID INTEGRAL MEMBRANE-PROTEIN; MANNOSE 6-PHOSPHATE RECEPTOR; ENDOPLASMIC-RETICULUM; CELL-SURFACE; PRELYSOSOMAL COMPARTMENT; KEX2-LIKE ENDOPROTEASE; ENDOCYTIC PATHWAY; BREFELDIN-A; LYSOSOMES; EXPRESSION AB To investigate the mechanisms of membrane protein localization to the Golgi complex, we have examined the intracellular trafficking of epitope-tagged forms of the mammalian endopeptidase, furin, in stably transformed rat basophilic leukemia cells. Our studies show that furin is predominantly localized to the trans-Golgi network (TGN) at steady state, with smaller amounts present in intracellular vesicles. Biochemical and morphological analyses reveal that furin is progressively delivered to a lysosomal compartment, where it is degraded. Analyses of furin deletion mutants and chimeric proteins show that the cytoplasmic domain is both necessary and sufficient for localization to the TGN in various cell types. Interestingly, deletion of most of the cytoplasmic domain of furin results in a molecule that is predominantly localized to intracellular vesicles, some of which display characteristics of lysosomes. To a lesser extent, the cytoplasmically deleted molecule is also localized to the plasma membrane. These observations suggest the existence of an additional determinant for targeting to the endosomal/lysosomal system within the lumenal and/or transmembrane domains of furin. Thus, the overall pattern of trafficking and steady state localization of furin are determined by targeting information contained within more than one region of the molecule. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. NINCDS,NEUROBIOL LAB,BETHESDA,MD 20892. UNIV UTRECHT,SCH MED,DEPT CELL BIOL,3584 CX UTRECHT,NETHERLANDS. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 62 TC 142 Z9 142 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD SEP PY 1994 VL 126 IS 5 BP 1157 EP 1172 DI 10.1083/jcb.126.5.1157 PG 16 WC Cell Biology SC Cell Biology GA PD427 UT WOS:A1994PD42700005 PM 7914893 ER PT J AU LAFLAMME, SE THOMAS, LA YAMADA, SS YAMADA, KM AF LAFLAMME, SE THOMAS, LA YAMADA, SS YAMADA, KM TI SINGLE SUBUNIT CHIMERIC INTEGRINS AS MIMICS AND INHIBITORS OF ENDOGENOUS INTEGRIN FUNCTIONS IN RECEPTOR LOCALIZATION, CELL SPREADING AND MIGRATION, AND MATRIX ASSEMBLY SO JOURNAL OF CELL BIOLOGY LA English DT Article ID CYTOPLASMIC DOMAIN; FIBRONECTIN RECEPTOR; EXTRACELLULAR-MATRIX; FOCAL ADHESIONS; BETA-SUBUNIT; INTERLEUKIN-2 RECEPTOR; LIVING FIBROBLASTS; ALPHA; PROTEIN; VITRONECTIN AB The ability of single subunit chimeric receptors containing various integrin beta intracellular domains to mimic and/or inhibit endogenous integrin function was examined. Chimeric receptors consisting of the extracellular and transmembrane domains of the small subunit of the human interleukin-2 receptor connected to either the beta(1), beta(3), beta(3B), or beta(5) intracellular domain were transiently expressed in normal human fibroblasts. When expressed at relatively low levels, the beta(3) and beta(5) chimeras mimicked endogenous ligand-occupied integrins and, like the beta(1) chimera (LaFlamme, S. E., S. K. Akiyama, and K. M. Yamada. 1992. J. Cell Biol. 117:437), concentrated with endogenous integrins in focal adhesions and sites of fibronectin fibril formation. In contrast, the chimeric receptor containing the beta(3B) intracellular domain (a beta(3) intracellular domain modified by alternative splicing) was expressed diffusely on the cell surface, indicating that alternative splicing can regulate integrin receptor distribution by an intracellular mechanism. Furthermore, when expressed at higher levels, the beta(1) and beta(3) chimeric receptors functioned as dominant negative mutants and inhibited endogenous integrin function in localization to fibronectin fibrils, fibronectin matrix assembly, cell spreading, and cell migration. The beta(5) chimera was a less effective inhibitor, and the beta(3B) chimera and the reporter lacking an intracellular domain did not inhibit endogenous integrin function. Comparison of the relative levels of expression of the transfected beta(1) chimera and the endogenous beta(1) subunit indicated that in 10 to 15 h assays, the beta(1) chimera can inhibit cell spreading when expressed at levels approximately equal to to the endogenous beta(1) subunit. Levels of chimeric receptor expression that inhibited cell spreading also inhibited cell migration, whereas lower levels were able to inhibit alpha(5) beta(1) localization to fibrils and matrix assembly. Our results indicate that single subunit chimeric integrins can mimic and/or inhibit endogenous integrin receptor function, presumably by interacting with cytoplasmic components critical for endogenous integrin function. Our results also demonstrate that beta intracellular domains, expressed in this context, display specificity in their abilities to mimic and inhibit endogenous integrin function. Furthermore, the approach that we have used permits the analysis of intracellular domain function in the processes of cell spreading, migration and extracellular matrix assembly independent of effects due to the rest of integrin dimers. This approach should prove valuable in the further analysis of integrin intracellular domain function in these and other integrin-mediated processes requiring the interaction of integrins with cytoplasmic components. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. OI Yamada, Kenneth/0000-0003-1512-6805 NR 70 TC 215 Z9 217 U1 1 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD SEP PY 1994 VL 126 IS 5 BP 1287 EP 1298 DI 10.1083/jcb.126.5.1287 PG 12 WC Cell Biology SC Cell Biology GA PD427 UT WOS:A1994PD42700017 PM 8063864 ER PT J AU CAMPOCHIARO, PA HACKETT, SF VINORES, SA FREUND, J CSAKY, C LAROCHELLE, W HENDERER, J JOHNSON, M RODRIGUEZ, IR FRIEDMAN, Z DEREVJANIK, N DOONER, J AF CAMPOCHIARO, PA HACKETT, SF VINORES, SA FREUND, J CSAKY, C LAROCHELLE, W HENDERER, J JOHNSON, M RODRIGUEZ, IR FRIEDMAN, Z DEREVJANIK, N DOONER, J TI PLATELET-DERIVED GROWTH-FACTOR IS AN AUTOCRINE GROWTH STIMULATOR IN RETINAL PIGMENTED EPITHELIAL-CELLS SO JOURNAL OF CELL SCIENCE LA English DT Article DE PLATELET-DERIVED GROWTH FACTOR; RETINAL PIGMENTED EPITHELIUM; PROLIFERATIVE RETINOPATHY ID FACTOR-A-CHAIN; SMOOTH-MUSCLE CELLS; MESSENGER-RNA; PROLIFERATIVE VITREORETINOPATHY; RHEUMATOID SYNOVIUM; MITOGENIC ACTIVITY; FACTOR RECEPTORS; GENE-EXPRESSION; FACTOR PDGF; FACTOR-I AB The retinal pigmented epithelium (RPE) plays a major role in normal and exaggerated retinal wound repair; the latter can result in epiretinal membrane formation and loss of vision. The RPE forms a stable monolayer of highly differentiated cells that proliferates only during wound repair. The mechanism underlying the change to the proliferating phenotype is unknown. When grown on a plastic substratum, cultured RPE cells mimic the proliferating phenotype in situ; they escape density arrest and proliferate in serum-free medium. In this study, we have demonstrated that a platelet-derived growth factor (PDGF) autocrine loop is involved in RPE growth in serum-free medium, because: (1) RPE cells secrete PDGF into their media and express PDGF receptors; (2) the PDGF receptors on RPE cells are autophosphorylated in serum-free medium and suramin, an agent that displaces PDGF and other growth factors from their receptors, blocks the autophosphorylation; and (3) a neutralizing antibody to PDGF significantly decreases RPE growth in serum-free medium. When a linear scrape is made in an RPE monolayer, the cells migrate and proliferate to fill in the gap mimicking wound repair in situ. Cells along the edge of the scrape show increased expression of PDGF and PDGF-beta receptors, and increased staining for proliferating cell nuclear antigen. Immunohistochemistry and in situ hybridization demonstrate expression of PDGF in ganglion cells and cells of retinal blood vessels. PDGF is not detected in the outer retina or RPE in untreated eyes, but is detected in RPE participating in wound repair, either adjacent to laser burns or underlying retinal detachment. PDGF and PDGF receptors are also expressed in RPE in epiretinal membranes removed during vitreous surgery. These data suggest that PDGF is an autocrine stimula tor of growth in RPE that plays a role in retinal wound repair and epiretinal membrane formation. C1 NIH, BETHESDA, MD USA. RP CAMPOCHIARO, PA (reprint author), JOHNS HOPKINS UNIV HOSP, WILMER INST, 719 MAUMENEE BLDG, 600 N WOLFE ST, BALTIMORE, MD 21287 USA. FU NEI NIH HHS [EY05951, P30EY01765] NR 52 TC 137 Z9 144 U1 0 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD SEP PY 1994 VL 107 BP 2459 EP 2469 PN 9 PG 11 WC Cell Biology SC Cell Biology GA PH545 UT WOS:A1994PH54500011 PM 7844163 ER PT J AU MESRI, EA ONO, M KREITMAN, RJ KLAGSBRUN, M PASTAN, I AF MESRI, EA ONO, M KREITMAN, RJ KLAGSBRUN, M PASTAN, I TI THE HEPARIN-BINDING DOMAIN OF HEPARIN-BINDING EGF-LIKE GROWTH-FACTOR CAN TARGET PSEUDOMONAS EXOTOXIN TO KILL CELLS EXCLUSIVELY THROUGH HEPARAN-SULFATE PROTEOGLYCANS SO JOURNAL OF CELL SCIENCE LA English DT Article DE IMMUNOTOXINS; PSEUDOMONAS EXOTOXIN A; SMOOTH MUSCLE CELLS; CANCER CELLS; ANTITUMOR AGENTS; HEPARIN ID SMOOTH-MUSCLE CELLS; FIBROBLAST GROWTH; CYTOTOXIC ACTIVITY; CHIMERIC TOXINS; MESSENGER-RNA; FACTOR FAMILY; RECEPTOR; SURFACE; ATHEROSCLEROSIS; PROTEINS AB Heparin-binding EGF-like growth factor (HB-EGF) is a smooth muscle cell mitogen composed of both EGF receptor and heparin-binding domains. To better understand the function of its domains, intact HB-EGF or its heparin-binding (HB) domain (amino acids 1-45) were fused to a mutant Pseudomonas exotoxin with an inactivated cell-binding domain. The resulting chimeric toxins, HB-EGF-PE* and HB-PE*, were tested on tumor cells, proliferating smooth muscle cells and a mutant Chinese hamster ovary cell line deficient in heparan sulfate proteoglycans (HSPGs). Two targets were found for HB-EGF-PE*. Cells were killed mainly through EGF receptors, but the HB domain was responsible for killing via HSPGs. HB-PE* did not bind to the EGF receptor and thus was cytotoxic by interacting exclusively with HSPGs. We conclude that the HB domain of HB-EGF is able to mediate internalization through HSPGs, without requiring the EGF receptor. C1 NCI, DIV CANC BIOL DIAG & CTR, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. CHILDRENS HOSP, DEPT BIOL CHEM & MOLEC PHARMACOL, BOSTON, MA 02115 USA. NR 53 TC 14 Z9 14 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 EI 1477-9137 J9 J CELL SCI JI J. Cell Sci. PD SEP PY 1994 VL 107 BP 2599 EP 2608 PN 9 PG 10 WC Cell Biology SC Cell Biology GA PH545 UT WOS:A1994PH54500024 PM 7844173 ER PT J AU FIORELLI, G BALLOCK, RT WAKEFIELD, LM SPORN, MB GORI, F MASI, L FREDIANI, U TANINI, A BERNABEI, PA BRANDI, ML AF FIORELLI, G BALLOCK, RT WAKEFIELD, LM SPORN, MB GORI, F MASI, L FREDIANI, U TANINI, A BERNABEI, PA BRANDI, ML TI ROLE FOR AUTOCRINE TGF-BETA-1 IN REGULATING DIFFERENTIATION OF A HUMAN LEUKEMIC-CELL LINE TOWARD OSTEOCLAST-LIKE CELLS SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID TRANSFORMING GROWTH-FACTOR; FACTOR-BETA; BONE-RESORPTION; TGF-BETA; MARROW CULTURES; EXPRESSION; MODULATION; RECEPTORS; COMPLEX; CLONING AB Increasing evidence suggests that transforming growth factor-beta (TGF-beta) is involved in bone formation during remodeling. Using a recently cloned human leukemic cell line (FLG 29.1 cells) we demonstrate that these cells synthesize and secrete TGF-beta 1 and that exogenous or autocrine TGF-beta 1 can induce the same features of osteoclastic-like cells, exerting its effects through the binding to TGF-beta specific receptors. Scatchard analysis of I-125-labeled TGF-beta 1 to FLG 29.1 cells revealed the presence of a single high affinity binding site with a Kd value of similar to 25 pM and a binding capacity of similar to 900 sites/cell. Affinity labeling experiments showed that FLG 29.1 cells express type I and type II TGF-beta receptors. Stimulation of FLG 29.1 cells with low TGF-beta 1 doses reduced cell proliferation and increased cell adhesion and tartrate resistant acid phosphatase (TRAcP) activity. Pretreatment of FLG 29.1 cells with TGF-beta 1 caused a significant and dose-dependent response to calcitonin. Northern blot of total mRNA and analysis of the conditioned media (CM) showed that TGF-beta 1 was synthesized by FLG 29.1 cells. TPA treatment, which induces partial differentiation of these cells, markedly increased TGF-beta 1 mRNA expression and growth factor release. The majority of TGF-beta 1 secreted by TPA-treated cells was in its latent form. However, anti-TGF-beta antibodies inhibited TGF-beta 1 and TPA-induced growth inhibition, calcitonin responsiveness, and TRAcP activity, suggesting that the TPA effect is mediated in part by autocrine TGF-beta 1 and indicating that the cells can activate and respond to the TGF-beta that they secrete. These findings support a potential autocrine role for TGF-beta 1 in osteoclast differentiation. (C) 1994 Wiley-Liss, Inc. C1 UNIV FLORENCE,DEPT CLIN PHYSIOPATHOL,ENDOCRINE UNIT,I-50139 FLORENCE,ITALY. UNIV FLORENCE,INST INTERNAL MED 3,I-50139 FLORENCE,ITALY. UNIV FLORENCE,UO HEMATOL,I-50139 FLORENCE,ITALY. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NR 44 TC 21 Z9 21 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 SEP PY 1994 VL 160 IS 3 BP 482 EP 490 DI 10.1002/jcp.1041600311 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA PF218 UT WOS:A1994PF21800010 PM 8077286 ER PT J AU MILNE, GWA NICKLAUS, MC DRISCOLL, JS WANG, SM ZAHAREVITZ, D AF MILNE, GWA NICKLAUS, MC DRISCOLL, JS WANG, SM ZAHAREVITZ, D TI NATIONAL-CANCER-INSTITUTE DRUG INFORMATION-SYSTEM 3D DATABASE SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Article ID PROTEIN-KINASE-C; CHEMICAL STRUCTURES; TUMOR PROMOTERS; CRYSTALLOGRAPHIC DATA; INTERMEDIATE NEGLECT; ALGORITHMS; SELECTION; CAMBRIDGE; MODULE; SEARCH AB A searchable database of three-dimensional structures has been developed from the chemistry database of the NCI Drug Information System (DIS), a file of about 450 000 primarily organic compounds which have been tested by NCI for anticancer activity. The DIS database is very similar in size and content to the proprietary databases used in the pharmaceutical industry; its development began in the 1950s; and this history led to a number of problems in the generation of 3D structures. C1 NCI,DIV CANC TREATMENT,MED CHEM LAB,BETHESDA,MD 20892. RP MILNE, GWA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK,MD 21702, USA. RI Nicklaus, Marc/N-4183-2014 NR 43 TC 107 Z9 113 U1 2 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0095-2338 J9 J CHEM INF COMP SCI JI J. Chem. Inf. Comput. Sci. PD SEP-OCT PY 1994 VL 34 IS 5 BP 1219 EP 1224 DI 10.1021/ci00021a032 PG 6 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA PJ459 UT WOS:A1994PJ45900033 PM 7962217 ER PT J AU ARNOLD, LE KLEYKAMP, D VOTOLATO, N GIBSON, RA HORROCKS, L AF ARNOLD, LE KLEYKAMP, D VOTOLATO, N GIBSON, RA HORROCKS, L TI POTENTIAL LINK BETWEEN DIETARY-INTAKE OF FATTY-ACIDS AND BEHAVIOR - PILOT EXPLORATION OF SERUM-LIPIDS IN ATTENTION-DEFICIT HYPERACTIVITY DISORDER SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article AB Essential fatty acids are structural components of all biological membranes and form the environment for membrane receptors, ion channels, and enzymes. Dietary linoleic acid is metabolized by delta-6-desaturase to gamma-linolenic acid (GLA). Through several further metabolic steps, GLA is eventually converted to series-1 prostaglandins, thromboxanes, and other molecules involved in regulating the moment-to-moment function of various physiological processes. For example, prostaglandins interact with dopamine neurotransmission. The biochemistry and physiology of essential fatty acids are reviewed, with attention to possible implications for behavior. Delta-6-desaturase deficiency has been hypothesized to be one cause of attention-deficit hyperactivity disorder (ADHD). To explore this possibility, we examined the correlations of serum lipids and behavior in a double-blind crossover comparison of GLA, d-amphetamine, and placebo in 16 boys (ages 6-12) with ADHD. Looking at the fatty-acid components of serum triglycerides across treatment conditions, we found that higher scores for behavior problems correlated with lower levels of GLA (for each of four behavioral ratings, p < 0.015) but not with its precursor, linoleic acid. This is compatible with a metabolic bottleneck at delta-6-desaturase being related to some ADHD symptoms. These preliminary findings are consistent with the possibility that fatty-acid intake or metabolism may influence behavior, at least in children with ADHD, and could conceivably modulate the effects of psychopharmacological treatment. This study must be considered exploratory and heuristic, and more definitive studies are needed to examine the possible relevance of fatty-acid metabolism to psychiatric disorders. RP ARNOLD, LE (reprint author), NIMH,CHILD & ADOLESCENT DISORDERS RES BRANCH,PARKLAWN 18C-17,ROCKVILLE,MD 20857, USA. RI Gibson, Robert/E-7546-2012 OI Gibson, Robert/0000-0002-8750-525X NR 0 TC 21 Z9 22 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD FAL PY 1994 VL 4 IS 3 BP 171 EP 182 DI 10.1089/cap.1994.4.171 PG 12 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA PK771 UT WOS:A1994PK77100004 ER PT J AU SHENKER, A WEINSTEIN, LS SWEET, DE SPIEGEL, AM AF SHENKER, A WEINSTEIN, LS SWEET, DE SPIEGEL, AM TI AN ACTIVATING G(S)ALPHA MUTATION IS PRESENT IN FIBROUS DYSPLASIA OF BONE IN THE MCCUNE-ALBRIGHT SYNDROME SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID STIMULATORY G-PROTEIN; ALPHA-SUBUNIT; HEREDITARY OSTEODYSTROPHY; ADENYLYL CYCLASE; DIFFERENTIATION; GENE; CELLS; ENDOCRINE; RECEPTORS; INVITRO AB McCune-Albright syndrome (MAS) is a sporadic disease characterized by polyostotic fibrous dysplasia, cafe-au-lait spots, and multiple endocrinopathies. The etiology of fibrous dysplasia is unknown. Activating mutations of codon 201 in the gene encoding the alpha-subunit of G(B), the G-protein that stimulates adenylyl cyclase, have been found in all affected MAS tissues that have been studied. Initial attempts to amplify DNA from decalcified paraffin-embedded bone specimens from MAS patients were unsuccessful. Therefore, we analyzed DNA from frozen surgical bone specimens from five MAS patients using polymerase chain reaction and allele-specific oligonucleotide hybridization. Most of the cells in four specimens of dysplastic bone contained a heterozygous mutation encoding substitution of Arg(201) of G(B) alpha with His, but the mutation was barely detectable in peripheral blood specimens from the patients. Only a small amount of mutant allele was detected in a specimen of normal cortical bone from the fifth patient, although this patient had a high proportion of mutation in other, affected tissues. The mosaic distribution of mutant alleles is consistent with an embryological somatic cell mutation of the G,cu gene in MAS. The presence of an activating mutation of G,cu in osteoblastic progenitor cells may cause them to exhibit increased proliferation and abnormal differentiation, thereby producing the lesions of fibrous dysplasia. C1 ARMED FORCES INST PATHOL, DEPT ORTHOPED PATHOL, WASHINGTON, DC 20306 USA. RP SHENKER, A (reprint author), NIDDKD, METAB DIS BRANCH, MOLEC PATHOPHYSIOL SECT, BLDG 10, ROOM 8C-101, BETHESDA, MD 20892 USA. OI Weinstein, Lee/0000-0002-1899-5152 NR 44 TC 147 Z9 150 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1994 VL 79 IS 3 BP 750 EP 755 DI 10.1210/jc.79.3.750 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PF386 UT WOS:A1994PF38600012 PM 8077356 ER PT J AU FLACK, MR BENNET, AP FROEHLICH, J ANASTI, JN NISULA, BC AF FLACK, MR BENNET, AP FROEHLICH, J ANASTI, JN NISULA, BC TI INCREASED BIOLOGICAL-ACTIVITY DUE TO BASIC ISOFORMS IN RECOMBINANT HUMAN FOLLICLE-STIMULATING-HORMONE PRODUCED IN A HUMAN CELL-LINE SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HAMSTER OVARY CELLS; HUMAN FSH; HYPOPHYSECTOMIZED RATS; AROMATASE BIOASSAY; HUMAN FOLLITROPIN; INVITRO; BIOACTIVITY; EXPRESSION; SECRETION; CHARGE AB FSH has four asparagine-linked oligosaccharides with variable sialic acid contents, so that FSH is not a single molecule, but a heterogeneous group of isoforms. These isoforms differ in their biological properties and their distribution changes in various physiological states, allowing the modulation of FSH activity. Recombinant human (h) FSH has been produced in Chinese hamster ovary cells and has an isoform profile similar to those of both pituitary FSH standard and purified urinary FSH. These FSH preparations, however, do not contain the full spectrum of FSH isoforms found in the circulation. Production of recombinant hFSH in a cell line with a different pattern of glycosylation could broaden its isoform profile and potentially alter its biological activity. Thus, we transfected human embryonal kidney cells (293) with the human alpha and FSH beta genes to produce recombinant hFSH (hFSH-293) and determined its biological activity in a rat granulosa cell bioassay. Although hFSH-293 was immunologically indistinguishable from pituitary FSH standard, its biological potency was 3- to 6-fold higher than those of two different pituitary FSH standards. To investigate this increased potency, we separated the isoforms of hFSH-293 by chromatofocusing and determined their biological potencies in the rat granulosa cell bioassay. The isoform profile of hFSH-293 demonstrated a greater number of basic isoforms than that of pituitary FSH standard. Several of these basic isoforms exhibited enhanced in vitro biological potency, accounting for the increased biological potency of hFSH-293. This pattern of high in vitro biological activity and more basic isoforms is analogous to the FSH circulating during GnRH stimulation, pubertal induction, and ovulation. RP NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N262, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 26 TC 49 Z9 50 U1 0 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1994 VL 79 IS 3 BP 756 EP 760 DI 10.1210/jc.79.3.756 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PF386 UT WOS:A1994PF38600013 PM 8077357 ER PT J AU MICHELSON, D STONE, L GALLIVEN, E MAGIAKOU, MA CHROUSOS, GP STERNBERG, EM GOLD, PW AF MICHELSON, D STONE, L GALLIVEN, E MAGIAKOU, MA CHROUSOS, GP STERNBERG, EM GOLD, PW TI MULTIPLE-SCLEROSIS IS ASSOCIATED WITH ALTERATIONS IN HYPOTHALAMIC-PITUITARY-ADRENAL AXIS FUNCTION SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; CENTRAL NERVOUS-SYSTEM; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CEREBROSPINAL-FLUID; CORTISOL SECRETION; LEWIS RATS; VASOPRESSIN; ACTIVATION; CORTICOSTEROIDS; SUSCEPTIBILITY AB In the LEW/N rat model, a decreased hypothalamic-pituitary-adrenal (HPA) axis response to inflammatory and immune mediators confers susceptibility to the development of a variety of inflammatory and immune diseases, including experimental allergic encephalomyelitis. In humans with optic neuritis, early intervention with steroids is associated with a decrease in the number of patients who go on to develop multiple sclerosis (MS). The current study was designed to determine whether patients with MS show evidence of a hypoactive HPA axis. Thirteen patients with MS were studied at baseline and with provocative tests of HPA axis function [ovine CRH, arginine vasopressin (AVP), and ACTH stimulation]. Compared to matched controls, patients with MS had significantly higher plasma cortisol levels at baseline. Despite this hypercortisolism and in contrast to patients with depression who had similar elevations in plasma cortisol levels, patients with MS showed normal, rather than blunted, plasma ACTH responses to ovine CRH, suggesting that the pathophysiology of hypercortisolism in MS is different from that in depression. Patients with MS also showed blunted ACTH responses to AVP stimulation and normal cortisol responses to high and low dose ACTH stimulation. Taken together, these findings are compatible with data from studies of experimental animals exposed to chronic inflammatory stress, which showed mild increased activation of the HPA axis with increased relative activity of AVP in the regulation of the pituitary-adrenal axis. These data do not support a role for hypocortisolism in MS once the disease is established. C1 NINCDS, NEUROIMMUNOL BRANCH, BETHESDA, MD 20892 USA. NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. RP MICHELSON, D (reprint author), NIMH, CLIN NEUROENDOCRINOL BRANCH, BLDG 10, ROOM 3S231, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 27 TC 121 Z9 123 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1994 VL 79 IS 3 BP 848 EP 853 DI 10.1210/jc.79.3.848 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PF386 UT WOS:A1994PF38600029 PM 8077372 ER PT J AU JAFFE, JS JAMES, SP MULLINS, GE BRAUNELWERT, L LUBENSKY, I METCALFE, DD AF JAFFE, JS JAMES, SP MULLINS, GE BRAUNELWERT, L LUBENSKY, I METCALFE, DD TI EVIDENCE FOR AN ABNORMAL PROFILE OF INTERLEUKIN-4 (IL-4), IL-5, AND GAMMA-INTERFERON (GAMMA-IFN) IN PERIPHERAL-BLOOD T-CELLS FROM PATIENTS WITH ALLERGIC EOSINOPHILIC GASTROENTERITIS SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE CYTOKINES; LYMPHOKINES; ALLERGY; IGE; EOSINOPHILS ID INTESTINAL INTRAEPITHELIAL LYMPHOCYTES; RECOMBINANT HUMAN INTERLEUKIN-5; HUMAN B-CELLS; MONOCLONAL-ANTIBODIES; CYTOKINE SYNTHESIS; IGE PRODUCTION; INVITRO; ANTIGEN; CLONES; PROLIFERATION AB Allergic eosinophilic gastroenteritis is characterized by elevated total IgE, specific IgE to food antigens, and eosinophilia of tissue and blood. Because the lymphokines IL-4, IL-5, and gamma-interferon, regulate IgE synthesis, and eosinophilopoiesis in vitro, we examined whether there is an imbalance in their production in allergic eosinophilic gastroenteritis. To explore this hypothesis, three adult patients with allergic eosinophilic gastroenteritis were studied. Flow cytometric studies of peripheral blood mononuclear cells from these patients did not reveal evidence of T cell activation or disturbance of T cell numbers or subsets. T cells were capable of normal mitogenic activation in vitro. IL-4 and IL-5 production were markedly elevated with mitogenic stimulation. Most IL-4 and IL-5 production was by CD4(+) T cells. Synthesis of IL-5 by CD4(+) T lymphocytes in three patients and CD8(+) T lymphocytes in two patients occurred in the absence of mitogen. Mitogen-stimulated GM-CSF and gamma-interferon synthesis by CD4(+) T cells was normal. Lymphokine mRNA in total cellular RNA derived from endoscopic biopsies was examined by reverse transcription/polymerase chain reaction. Mucosal biopsies from control subjects and most biopsies from allergic eosinophilic gastroenteritis patients contained less than 10(-8) mu g IL-5 mRNA/1 mu g total cellular mRNA. gamma-Interferon mRNA was not detected by reverse transcription/polymerase chain reaction in biopsies from patients with allergic eosinophilic gastroenteritis but was present in controls. These lymphokine abnormalities are consistent with the elevated IgE and eosinophilia seen in allergic eosinophilic gastroenteritis and suggest that strategies targeting T lymphocytes may be efficacious in treatment of this disease. C1 NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. NR 51 TC 53 Z9 56 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD SEP PY 1994 VL 14 IS 5 BP 299 EP 309 DI 10.1007/BF01540983 PG 11 WC Immunology SC Immunology GA PJ121 UT WOS:A1994PJ12100005 PM 7814459 ER PT J AU BERZOFSKY, JA AF BERZOFSKY, JA TI PRESIDENTIAL-ADDRESS TO THE AMERICAN-SOCIETY-FOR-CLINICAL-INVESTIGATION, BALTIMORE, MARYLAND, 30-APRIL-1994 - CROSS-FERTILIZATION AMONG FIELDS - A SEMINAL EVENT IN THE PROGRESS OF BIOMEDICAL-RESEARCH SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID T-CELLS; PROTEIN RP BERZOFSKY, JA (reprint author), NCI,METAB BRANCH,MOLEC IMMUNOGENET & VACCINE RES SECT,BLDG 10,ROOM 6B-12,BETHESDA,MD 20892, USA. NR 14 TC 3 Z9 3 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1994 VL 94 IS 3 BP 911 EP 918 DI 10.1172/JCI117455 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PF354 UT WOS:A1994PF35400001 PM 8083374 ER PT J AU BRADY, LS LYNN, AB GLOWA, JR LE, DQ HERKENHAM, M AF BRADY, LS LYNN, AB GLOWA, JR LE, DQ HERKENHAM, M TI REPEATED ELECTROCONVULSIVE SHOCK PRODUCES LONG-LASTING INCREASES IN MESSENGER-RNA EXPRESSION OF CORTICOTROPIN-RELEASING HORMONE AND TYROSINE-HYDROXYLASE IN RAT-BRAIN - THERAPEUTIC IMPLICATIONS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE CORTICOTROPIN; MELANCHOLIC DEPRESSION; ELECTROCONVULSIVE THERAPY; HYPOTHALAMUS; LOCUS COERULEUS ID PITUITARY-ADRENAL AXIS; DEPRESSED-PATIENTS; BIOCHEMICAL MANIFESTATIONS; MINERALOCORTICOID RECEPTOR; CEREBROSPINAL-FLUID; CUSHINGS-DISEASE; BETA-ENDORPHIN; STRESS; NEUROBIOLOGY; RESPONSES AB Electroconvulsive shock (ECS) is a highly effective therapy for the treatment of major depression, but its mechanisms of action are not known. We report that repeated ECS in rats produces enduring changes in two clinically relevant stress-responsive brain systems: (a) the hypothalamic-pituitary-adrenal axis regulated by corticotropin-releasing hormone (CRH) in the paraventricular nucleus; and (b) the NE system in the locus coeruleus regulated by tyrosine hydroxylase (TH). CRH and TH mRNA levels in these brain regions were assessed by in situ hybridization histochemistry. A single interaural ECS elevated TH but not CRH mRNA measured 24 h later. Repeated daily treatments (3, 7, or 14) elevated both mRNAs, maximally with 7, correlating with the time course of clinical efficacy. The elevations persisted for 3 (CRH) or 8 wk (TH) after the ECS. No other therapeutic treatment is known to produce such longlasting changes in central nervous system gene expression. The time course of events (delayed onset, long duration) implicate CRH as a principal mediator of the antidepressant effects of ECS. The locus coeruleus-NE system may be important in initiating the central nervous system response. RP BRADY, LS (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,FUNCT NEUROANAT SECT,BLDG 36,ROOM 2D-15,BETHESDA,MD 20892, USA. OI Herkenham, Miles/0000-0003-2228-4238 NR 42 TC 24 Z9 25 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1994 VL 94 IS 3 BP 1263 EP 1268 DI 10.1172/JCI117444 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PF354 UT WOS:A1994PF35400044 PM 7916018 ER PT J AU JAPOUR, AJ FISCUS, SA ARDUINO, JM MAYERS, DL REICHELDERFER, PS KURITZKES, DR AF JAPOUR, AJ FISCUS, SA ARDUINO, JM MAYERS, DL REICHELDERFER, PS KURITZKES, DR TI STANDARDIZED MICROTITER ASSAY FOR DETERMINATION OF SYNCYTIUM-INDUCING PHENOTYPES OF CLINICAL HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ISOLATES SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Note ID HIV-1 BIOLOGICAL PHENOTYPE; ZIDOVUDINE RESISTANCE; DISEASE PROGRESSION; CELL-CULTURE; INFECTION; AIDS; INDIVIDUALS; TROPISM; CLONES; MT-2 AB A standardized assay in 96-well microtiter plates for syncytium-inducing (SI) human immunodeficiency virus type 1 phenotype detection using MT-2 cells has been developed. SI variants were found in 67% of the patients with advanced human immunodeficiency virus disease. The occurrence of the SI phenotype increased with lower CD4(+) counts. There was no association between p24 antigenemia and the SI phenotype. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02215. UNIV N CAROLINA,DEPT MICROBIOL & IMMUNOL,CHAPEL HILL,NC 27599. WALTER REED ARMY INST RES,DEPT HIV DRUGS & GENE THERAPY,ROCKVILLE,MD 20850. NIAID,DIV AIDS,BETHESDA,MD 20892. UNIV COLORADO,HLTH SCI CTR,DIV INFECT DIS,DENVER,CO 80262. VET AFFAIRS MED CTR,DENVER,CO 80262. USN,INST MED RES,ROCKVILLE,MD. HARVARD UNIV,SCH PUBL HLTH,CTR STAT DATA ANAL,BOSTON,MA 02215. RP JAPOUR, AJ (reprint author), BETH ISRAEL HOSP,DEPT MED,DIV INFECT DIS,DANA 617,330 BROOKLINE AVE,BOSTON,MA 02215, USA. FU NIAID NIH HHS [AI 27659, AI 25868, AI 01101] NR 19 TC 79 Z9 79 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 SEP PY 1994 VL 32 IS 9 BP 2291 EP 2294 PG 4 WC Microbiology SC Microbiology GA PB541 UT WOS:A1994PB54100049 PM 7814561 ER PT J AU ENGLER, HD SHEA, YR AF ENGLER, HD SHEA, YR TI EFFECT OF POTENTIAL INTERFERENCE FACTORS ON PERFORMANCE OF ENZYME-IMMUNOASSAY AND LATEX AGGLUTINATION ASSAY FOR CRYPTOCOCCAL ANTIGEN SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Note ID CEREBROSPINAL-FLUID; RHEUMATOID-FACTOR; SERUM; PRONASE AB The PREMIER Cryptococcal Antigen Enzyme Immunoassay (Meridian Diagnostics) did not give discrepant results with rheumatoid factor, syneresis fluid, or serum macroglobulins from systemic lupus erythematosis patients. The Cryptococcal Antigen Latex Agglutination System (Meridian Diagnostics) did cross-react with syneresis fluid but not with the other serum factors tested. RP ENGLER, HD (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT CLIN PATHOL,MICROBIOL SERV,BLDG 10,ROOM 2C-385,BETHESDA,MD 20892, USA. NR 11 TC 18 Z9 21 U1 0 U2 1 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 SEP PY 1994 VL 32 IS 9 BP 2307 EP 2308 PG 2 WC Microbiology SC Microbiology GA PB541 UT WOS:A1994PB54100054 PM 7814565 ER PT J AU JOHNSON, TP FORD, L WARNECKE, RB NAYFIELD, SG KALUZNY, A CUTTER, G GILLINGS, D SONDIK, E OZER, H AF JOHNSON, TP FORD, L WARNECKE, RB NAYFIELD, SG KALUZNY, A CUTTER, G GILLINGS, D SONDIK, E OZER, H TI EFFECT OF A NATIONAL-CANCER-INSTITUTE CLINICAL-ALERT ON BREAST-CANCER PRACTICE PATTERNS SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ADJUVANT THERAPY; PROGRAM; TUMORS AB Purpose: This study evaluates the effect of the 1988 National Cancer Institute Clinical Alert regarding treatment of early-stage breast cancer on the patterns of treatment provided to patients. Patients and Methods: Data analyzed were collected from the hospital and outpatient records of 12,534 female patients with a primary diagnosis of breast cancer (stages I and II) initially diagnosed during the years 1983 through 1989. Results: Analyses revealed that the proportions of patients with a negative lymph node status diagnosed after the May 1988 Clinical Alert who received adjuvant treatment (tamoxifen and/or multidrug chemotherapy) were significantly greater than predicted from treatment trends established before the Alert's release. Proportions of patients with positive lymph node status receiving adjuvant therapy subsequent to the Alert's release, in contrast, did not fall outside the projected confidence intervals for that group. Additional analyses showed a significant effect of the Clinical Alert among several subgroups of node-negative patients. Conclusion: Findings suggest that the Clinical Alert mechanism, followed by publication in the peer-reviewed scientific literature, is an effective way to communicate important research findings to practitioners in the community. However, the Alert mechanism is controversial and should be used judiciously to ensure its credibility (C) 1994 by American Society of Clinical Oncology. C1 NCI,BETHESDA,MD. UNIV N CAROLINA,CHAPEL HILL,NC. QUINTILES INC,RES TRIANGLE PK,NC. PYTHAGARUS INC,BIRMINGHAM,AL. RP JOHNSON, TP (reprint author), UNIV ILLINOIS,SURVEY RES LAB,910 W VAN BUREN,SUITE 500,CHICAGO,IL 60607, USA. NR 19 TC 20 Z9 20 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP PY 1994 VL 12 IS 9 BP 1783 EP 1788 PG 6 WC Oncology SC Oncology GA PG300 UT WOS:A1994PG30000008 PM 8083701 ER PT J AU KNABLE, MB WEINBERGER, DR AF KNABLE, MB WEINBERGER, DR TI LIMBIC-PREFRONTAL CONNECTIVITY AND CLOZAPINE SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium-Clozapine 1994 CY FEB 25-26, 1994 CL GARDEN CITY, NY ID ATYPICAL ANTIPSYCHOTIC-DRUGS; PHASEOLUS-VULGARIS LEUCOAGGLUTININ; DOPAMINE RECEPTOR ANTAGONISTS; POSITRON EMISSION TOMOGRAPHY; C-FOS; HIPPOCAMPAL DAMAGE; RECOGNITION SITES; NUCLEUS-ACCUMBENS; RAT STRIATUM; HALOPERIDOL AB The mechanisms of the antipsychotic efficacy and side effect profile of clozapine are incompletely understood. In vivo pharmacologic studies suggest that while clozapine does produce D2 receptor blockade, its unusual clinical profile may relate to activity at other receptor sites and to anatomical areas outside the striatum. Rodent studies indicate that acute administration of clinical doses of antipsychotic drugs, including clozapine, induces Fos (the protein product of the immediate early gene, c-fos) in the nucleus accumbens. However, unlike typical antipsychotic drugs, clozapine does not induce Fos in the dorsal striatum and does induce Fos in medical portions of the prefrontal cortex. Clozapine seems to produce a unique signature effect on long-term neuronal metabolism in its induction of Fos in the shell of the nucleus accumbens and in the medical prefrontal cortex. Future in vivo studies of cerebral blood flow and glucose metabolism in human patients may help to elucidate the specificity and reproducibility of the effects of clozapine in the ventral striatum and prefrontal cortex. RP KNABLE, MB (reprint author), ST ELIZABETH HOSP,CTR NEUROSCI,NATL INST MENTAL HLTH,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032, USA. NR 33 TC 8 Z9 8 U1 1 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 1994 VL 55 IS 9 SU B BP 70 EP 73 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA PQ450 UT WOS:A1994PQ45000015 PM 7961578 ER PT J AU GOLDBERG, TE WEINBERGER, DR AF GOLDBERG, TE WEINBERGER, DR TI THE EFFECTS OF CLOZAPINE ON NEUROCOGNITION - AN OVERVIEW SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium-Clozapine 1994 CY FEB 25-26, 1994 CL GARDEN CITY, NY ID MONOZYGOTIC TWINS DISCORDANT; PSYCHIATRIC-SYMPTOMS; SCHIZOPHRENIA; RECEPTORS; DOPAMINE; MEMORY; CORTEX AB Clozapine has proved effective in alleviating a wide range of psychiatric symptoms in schizophrenia. Its effects on cognitive function in schizophrenia are more variable. Clozapine appears to have a salutary effect on some aspects of attention, response speed, and fluency, whereas it appears to have a mild but adverse effect on visual memory and some executive functions. This profile may be related to the affinity of clozapine for dopaminergic type I and muscarinic receptors and relative lack of affinity for dopaminergic type II receptors. RP GOLDBERG, TE (reprint author), NIMH,CTR NEUROSCI,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032, USA. NR 24 TC 65 Z9 66 U1 1 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 1994 VL 55 IS 9 SU B BP 88 EP 90 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA PQ450 UT WOS:A1994PQ45000019 PM 7525543 ER PT J AU PISCITELLI, SC FRAZIER, JA MCKENNA, K ALBUS, KE GROTHE, DR GORDON, CT RAPOPORT, JL AF PISCITELLI, SC FRAZIER, JA MCKENNA, K ALBUS, KE GROTHE, DR GORDON, CT RAPOPORT, JL TI PLASMA CLOZAPINE AND HALOPERIDOL CONCENTRATIONS IN ADOLESCENTS WITH CHILDHOOD-ONSET SCHIZOPHRENIA - ASSOCIATION WITH RESPONSE SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium-Clozapine 1994 CY FEB 25-26, 1994 CL GARDEN CITY, NY ID CLINICAL-RESPONSE AB Background: Plasma clozapine and haloperidol concentrations were studied in adolescents being treated for childhood-onset schizophrenia. Method: Eleven patients (9 boys, 2 girls; mean age = 14.1 +/- 2.1 years) received a 6-week blinded to open trial of clozapine. Five patients also received 6 weeks of blinded or open haloperidol. Doses were increased on an individual basis to a mean 6-week dose of 5.99 +/- 2.6 mg/kg/day for clozapine and 0.24 +/- 0.20 mg/kg/day for haloperidol. The Brief Psychiatric Rating Scale and Bunney Hamburg Rating Scale were completed weekly for each subject. Weekly blood samples were obtained during therapy and assayed by high performance liquid chromatography. Results: The mean clozapine level at Week 6 was 378.3 ng/mL and ranged from 77.5 to 1050 ng/mL. The mean Week 6 haloperidol level was 23.0 ng/mL (range, 6.2-44.3 ng/mL). The clozapine desmethyl and N-oxide metabolites achieved mean concentrations of 77% and 18%, respectively, of those of the parent compound. The mean ratio of haloperidol/reduced haloperidol was 4.48 (range, 0.76-8.76). Clozapine concentrations versus clinical benefit exhibited a consistent linear relationship among patients (correlation range, 0.26-0.96). Conversely, poor and inconsistent correlations between haloperidol concentrations and clinical effects were observed. No relationships were noted between clozapine or haloperidol dose and clinical effects. Conclusion: Adolescents with schizophrenia produce a greater amount of desmethylclozapine than previously seen in adults. Plasma clozapine concentrations appear to be related in a linear fashion to clinical improvement. C1 NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N-240,BETHESDA,MD 20892. NIH,CLIN PHARMACOKINET RES LAB,BETHESDA,MD 20892. NIH,DEPT CLIN CTR PHARM,CLIN SECT,BETHESDA,MD 20892. NR 16 TC 53 Z9 53 U1 0 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 1994 VL 55 IS 9 SU B BP 94 EP 97 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA PQ450 UT WOS:A1994PQ45000021 PM 7961584 ER PT J AU BREIER, A AF BREIER, A TI CLOZAPINE AND NORADRENERGIC FUNCTION - SUPPORT FOR A NOVEL HYPOTHESIS FOR SUPERIOR EFFICACY SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium-Clozapine 1994 CY FEB 25-26, 1994 CL GARDEN CITY, NY ID SCHIZOPHRENIC-PATIENTS; ANTIPSYCHOTIC-DRUGS; NOREPINEPHRINE; FLUPHENAZINE; RECEPTORS; BRAIN AB Because of its superior clinical efficacy, clozapine is considered the new ''reference'' antipsychotic agent. Currently, there is an intensive investigational effort attempting to delineate which of clozapine's many biochemical effects are important for its impressive clinical profile. In this paper, the effects of clozapine on noradrenergic function are examined. Preclinical and clinical studies indicate that clozapine selectively increases noradrenergic activity and norepinephrine outflow. Moreover, data are presented demonstrating that clozapine causes fivefold increases in plasma norepinephrine in schizophrenic patients and that these increases are related to its superior clinical efficacy. A novel hypothesis for its superior efficacy is proposed that involves complex actions on noradrenergic systems that results in robust norepinephrine outflow. Implications of heightened norepinephrine outflow are discussed. C1 NIMH,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. NR 21 TC 35 Z9 35 U1 1 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 1994 VL 55 IS 9 SU B BP 122 EP 125 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA PQ450 UT WOS:A1994PQ45000028 PM 7961555 ER PT J AU PICKAR, D OWEN, RR LITMAN, RE HSIAO, JK SU, TP AF PICKAR, D OWEN, RR LITMAN, RE HSIAO, JK SU, TP TI PREDICTORS OF CLOZAPINE RESPONSE IN SCHIZOPHRENIA SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium-Clozapine 1994 CY FEB 25-26, 1994 CL GARDEN CITY, NY ID FLUPHENAZINE AB The introduction of the atypical neuroleptic, clozapine, has had widespread influence not only on the treatment of the seriously mentally ill patient, but also on new drug development and on hypotheses of the pathophysiology of schizophrenia. While clozapine differs from traditional neuroleptics in its lack of extrapyramidal side effects (EPS), it also is distinct in its profile of neuro-transmitter receptor affinities. In our work examining the clinical and biological effects of clozapine in patients with schizophrenia, we have identified the presence of EPS during typical neuroleptic treatment as a consistent predictor of subsequent good response to clozapine. Further, our data suggest that clozapine should not be reserved for the most chronically ill patients, but rather be utilized in patients with less chronic courses of schizophrenia. Biological predictors of clozapine response are consistent with dopaminergic, serotonergic, and noradrenergic facets to its mechanism of action. RP PICKAR, D (reprint author), NIMH,EXPTL THERAPEUT BRANCH,CLIN STUDIES SECT,10-4N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 8 TC 35 Z9 35 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 1994 VL 55 IS 9 SU B BP 129 EP 132 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA PQ450 UT WOS:A1994PQ45000030 PM 7525541 ER PT J AU DUYN, JH VANGELDEREN, P BARKER, P FRANK, JA MATTAY, VS MOONEN, CTW AF DUYN, JH VANGELDEREN, P BARKER, P FRANK, JA MATTAY, VS MOONEN, CTW TI 3D BOLUS TRACKING WITH FREQUENCY-SHIFTED BURST MRI SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE BRAIN; BRAIN, PERFUSION; MAGNETIC RESONANCE IMAGING, TECHNIQUES; ARTERIES, OCCLUSION ID CEREBRAL BLOOD-FLOW; MEAN TRANSIT-TIME; COMPUTED-TOMOGRAPHY; CEREBROVASCULAR-DISEASE; ENERGY-METABOLISM; CONTRAST AGENTS; PERFUSION; VOLUME; NMR; BRAIN AB Objective: Our goal was to develop and test a 3D bolus-tracking MR technique for perfusion imaging of normal and pathological (infarcted) human brain. Materials and Methods: All experiments were performed on standard 1.5 T GE/Signa clinical scanners. Five normal volunteers and one patient with a subacute brain infarct were studied. Modified [frequency-shifted (FS)] BURST MRI was performed during injection of a bolus of Gd-DTPA (0.13 mmol/kg) in the antecubital vein. The 3D datasets were acquired with a time resolution of 2.2 s and an effective spatial resolution of 4.3 x 4.3 x 6.4 mm. Three-diemensional maps of blood volume and bolus arrival time were determined by fitting a synthetic curve to the intensity time course on a voxel-by-voxel basis. Results: Both relative cerebral blood volume and arrival time maps demonstrated sensitivity to regional differences in blood supply in both normal brain and in the subacute brain infarction. The transit time maps showed arrival time delays of 5-7 s within and around the infarct and confirmed the diagnosis of left middle cerebral artery occlusion. Conclusion: The results of the measurements on both normal and diseased human brain demonstrated the ability to acquire valuable 3D information about brain perfusion using FS BURST MRI. C1 NIMH,NCRR,BEIP,IN VIVO NMR RES CTR,BETHESDA,MD 20892. NIMH,CLIN BRAIN DISORDERS BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. RP DUYN, JH (reprint author), NIMH,OIR,DIAGNOST RADIOL RES LAB,BLDG 10,RM B1N-256,BETHESDA,MD 20892, USA. RI Duyn, Jozef/F-2483-2010; Moonen, Chrit/K-4434-2016 OI Moonen, Chrit/0000-0001-5593-3121 NR 38 TC 28 Z9 28 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 1994 VL 18 IS 5 BP 680 EP 687 DI 10.1097/00004728-199409000-00002 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PG292 UT WOS:A1994PG29200002 PM 8089313 ER PT J AU FULHAM, MJ DIETZ, MJ DUYN, JH SHIH, HHL ALGER, JR DICHIRO, G AF FULHAM, MJ DIETZ, MJ DUYN, JH SHIH, HHL ALGER, JR DICHIRO, G TI TRANSSYNAPTIC REDUCTION IN N-ACETYL-ASPARTATE IN CEREBELLAR DIASCHISIS - A PROTON MR SPECTROSCOPIC IMAGING STUDY SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE CEREBELLUM; DIASCHISIS; MAGNETIC RESONANCE SPECTROSCOPY; PROTON MAGNETIC RESONANCE IMAGING ID HUMAN-BRAIN; NMR-SPECTROSCOPY; GLUCOSE-UTILIZATION; MAGNETIC-RESONANCE; BLOOD-FLOW; METABOLISM; INFARCTION; TUMORS; INVIVO; DIFFERENTIATION AB Objective: To determine if the transneuronal cerebellar hemispheric metabolic asymmetry seen in crossed cerebellar diaschisis, and readily detected with positron emission tomography (PET), is associated with alterations in metabolite signal intensities on [H-1]MR spectroscopic (MRS) imaging when compared with the normal pattern and distribution of cerebellar metabolites. Materials and Methods: The pattern and distribution of metabolites [N-acetyl-aspartate (NAA), choline-containing compounds, creatine, phosphocreatine, and lactate] in the cerebellum, using [H-1]MRS imaging, were studied in a patient with documented long-standing (3 years duration) crossed cerebellar diaschisis and seven normal subjects. Cerebellar diaschisis was detected with fluorodeoxyglucose-PET imaging. Single slice [H-1]MRS imaging was carried out at 1.5 T. Results: There was a marked reduction in NAA signal intensity in the diaschitic cerebellar hemisphere but minimal reduction in choline and creatine signal intensities. The decrease in NAA signal intensity was most marked in the middle cerebellar peduncle and white matter of the diaschitic cerebellar hemisphere. In the normal subjects and in the uninvolved cerebellar hemisphere of the patient the NAA signal intensity was more prominent in the white matter than the cerebellar cortex. Conclusion: Our data indicate (a) transneuronal metabolic effects can be detected with [H-1]MRS imaging and (b) there is a differential distribution of metabolite signal intensities in the cerebellum with NAA signal intensity predominantly localized to axons of the cerebellar fiber tracts rather than neuronal cell bodies in the cortex and the converse is true for choline and creatine signal intensities. C1 NIH,WARREN G MAGNUSON CLIN CTR,NEUROIMAGING BRANCH,BETHESDA,MD 20892. NINCDS,DIAGNOST RADIOL RES LAB,BETHESDA,MD 20892. RI Duyn, Jozef/F-2483-2010 NR 36 TC 24 Z9 26 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 1994 VL 18 IS 5 BP 697 EP 704 DI 10.1097/00004728-199409000-00004 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PG292 UT WOS:A1994PG29200004 PM 8089315 ER PT J AU MIELE, L CORDELLAMIELE, E MANTILE, G PERI, A MUKHERJEE, AB AF MIELE, L CORDELLAMIELE, E MANTILE, G PERI, A MUKHERJEE, AB TI UTEROGLOBIN AND UTEROGLOBIN-LIKE PROTEINS - THE UTEROGLOBIN FAMILY OF PROTEINS SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Review DE UTEROGLOBIN; CLARA CELL 10 KDA PROTEIN; PROGESTERONE; CORTICOSTEROIDS; ENDOMETRIUM; TRACHEOBRONCHIAL EPITHELIUM; INFLAMMATION ID ANTIINFLAMMATORY PEPTIDES ANTIFLAMMINS; PLATELET-ACTIVATING-FACTOR; TISSUE-SPECIFIC EXPRESSION; CELL 10-KDA PROTEIN; AMINO-ACID-SEQUENCE; RABBIT UTEROGLOBIN; PHOSPHOLIPASE-A2 ACTIVITY; URINE PROTEIN-1; PANCREATIC PHOSPHOLIPASE-A2; PROGESTERONE-BINDING RP MIELE, L (reprint author), NICHHD,HUMAN GENET BRANCH,DEV GENET SECT,BLDG 10,RM 9S242,BETHESDA,MD 20892, USA. NR 78 TC 79 Z9 79 U1 0 U2 1 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 SEP PY 1994 VL 17 IS 8 BP 679 EP 692 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PM871 UT WOS:A1994PM87100014 PM 7868811 ER PT J AU MENON, RK STEPHAN, DA RAO, RH SHENORR, Z DOWNS, LS ROBERTS, CT LEROITH, D SPERLING, MA AF MENON, RK STEPHAN, DA RAO, RH SHENORR, Z DOWNS, LS ROBERTS, CT LEROITH, D SPERLING, MA TI TISSUE-SPECIFIC REGULATION OF THE GROWTH-HORMONE RECEPTOR GENE IN STREPTOZOCIN-INDUCED DIABETES IN THE RAT SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID BINDING-PROTEIN; FACTOR-I; SOMATOGENIC RECEPTORS; METABOLIC-CLEARANCE; SOMATOMEDIN-C; RENAL GROWTH; INSULIN; EXPRESSION; SERUM; MELLITUS AB Abnormalities of GH secretion and clearance are well-documented in poorly controlled insulin-dependent diabetes mellitus (IDDM), but the contribution of the receptor (GHR) and the GH-binding protein (GHBP) to these abnormalities has not been defined. We studied the expression of the GHR/GHBP gene in the livers, hearts and kidneys in streptozocin-induced diabetes (STZ-D) in the rat. GHR and GHBP mRNA levels were measured by Northern blot and ribonuclease protection assays. Whereas levels of GHR and GHBP mRNA were significantly decreased in Liver and heart of STZ-D rats when compared with the control group (P<0.01), GHR mRNA was significantly increased in the kidneys of STZ-D rats (P=0.03). Six days of insulin treatment did not significantly alter the levels of GHR/GHBP mRNA in the liver or heart of STZ-D rats, but significantly decreased GHBP mRNA (P=0.04) in the kidney. Circulating IGF-I was reduced, as was IGF-I mRNA in the liver and heart of STZ-D rats; only circulating IGF-I was restored by insulin treatment. Neither STZ-D nor insulin treatment affected IGF-I or IGF-I receptor mRNA concentrations in the kidney. We conclude that (1) STZ-D modulates the expression of the GHR/GHBP gene and (2) that these changes in GHR/GHBP mRNA concentrations are tissue-specific; STZ-D decreases GHR/GHBP mRNA in liver and heart tissue but increases GHR mRNA concentrations in the kidney. Our results indicate a role for decreased numbers of hepatic GHRs in the pathogenesis of resistance to GH's actions in terms of IGF-I generation and promotion of linear growth in IDDM. We postulate that increased GHR expression in the kidney may be involved in the renal complications of IDDM. C1 UNIV PITTSBURGH,SCH MED,DEPT PEDIAT,PITTSBURGH,PA 15213. UNIV PITTSBURGH,SCH MED,DEPT INTERNAL MED,PITTSBURGH,PA 15213. NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. RP MENON, RK (reprint author), CHILDRENS HOSP,DEPT PEDIAT,DIV ENDOCRINOL,3705 5TH AVE,PITTSBURGH,PA 15213, USA. OI Roberts, Charles/0000-0003-1756-5772 FU NICHD NIH HHS [1K08-HD00986, HD 28836] NR 46 TC 41 Z9 42 U1 0 U2 0 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL, ENGLAND BS12 4NQ SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD SEP PY 1994 VL 142 IS 3 BP 453 EP 462 DI 10.1677/joe.0.1420453 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PF548 UT WOS:A1994PF54800008 PM 7964296 ER PT J AU BALA, S ENGLUND, G KOVACS, J WAHL, L MARTIN, M SHER, A GAZZINELLI, RT AF BALA, S ENGLUND, G KOVACS, J WAHL, L MARTIN, M SHER, A GAZZINELLI, RT TI TOXOPLASMA-GONDII SOLUBLE PRODUCTS INDUCE CYTOKINE SECRETION BY MACROPHAGES AND POTENTIATE IN-VITRO REPLICATION OF A MONOTROPIC STRAIN OF HIV SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article; Proceedings Paper CT 3rd International Workshops on Opportunistic Protists CY JUN 24-29, 1994 CL CLEVELAND STATE UNIV, CLEVELAND, OH SP SOC OF PROTOZOOLOGIST HO CLEVELAND STATE UNIV ID TUMOR NECROSIS FACTOR; IMMUNODEFICIENCY-VIRUS TYPE-1; FACTOR-ALPHA; KAPPA-B; EXPRESSION; ACTIVATION C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NCI,DEPT CRIT CARE MED,BETHESDA,MD 20892. NIDR,BETHESDA,MD 20892. US FDA,DIV ANTIVIRAL DRUG PROD,ROCKVILLE,MD 20857. RP BALA, S (reprint author), NIAID,PARASIT DIS LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 7 TC 8 Z9 9 U1 0 U2 0 PU SOC PROTOZOOLOGISTS PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD SEP-OCT PY 1994 VL 41 IS 5 BP S7 EP S7 PG 1 WC Microbiology SC Microbiology GA PP283 UT WOS:A1994PP28300016 PM 7804268 ER PT J AU GAZZINELLI, RT HAYASHI, S WYSOCKA, M CARRERA, L KUHN, R MULLER, W ROBERGE, F TRINCHIERI, G SHER, A AF GAZZINELLI, RT HAYASHI, S WYSOCKA, M CARRERA, L KUHN, R MULLER, W ROBERGE, F TRINCHIERI, G SHER, A TI ROLE OF IL-12 IN THE INITIATION OF CELL-MEDIATED-IMMUNITY BY TOXOPLASMA-GONDII AND ITS REGULATION BY IL-10 AND NITRIC-OXIDE SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article; Proceedings Paper CT 3rd International Workshops on Opportunistic Protists CY JUN 24-29, 1994 CL CLEVELAND STATE UNIV, CLEVELAND, OH SP SOC OF PROTOZOOLOGIST HO CLEVELAND STATE UNIV C1 NEI,IMMUNOL LAB,BETHESDA,MD 20892. WISTAR INST ANAT & BIOL,HUMAN IMMUNOL LAB,PHILADELPHIA,PA 19104. UNIV COLOGNE,INST GENET,W-5000 COLOGNE,GERMANY. RP GAZZINELLI, RT (reprint author), NIAID,PARASIT DIS LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Muller, Werner/B-9044-2008 OI Muller, Werner/0000-0002-1297-9725 NR 5 TC 12 Z9 14 U1 0 U2 1 PU SOC PROTOZOOLOGISTS PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD SEP-OCT PY 1994 VL 41 IS 5 BP S9 EP S9 PG 1 WC Microbiology SC Microbiology GA PP283 UT WOS:A1994PP28300018 PM 7804285 ER PT J AU DENKERS, EY CASPAR, P SHER, A AF DENKERS, EY CASPAR, P SHER, A TI TOXOPLASMA-GONDII POSSESSES A SUPERANTIGEN ACTIVITY THAT SELECTIVELY EXPANDS MURINE T-CELL RECEPTOR V-BETA-5-BEARING CD8+ LYMPHOCYTES SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CLASS-II MOLECULES; STAPHYLOCOCCAL ENTEROTOXIN-B; NATURAL-KILLER-CELLS; IFN-GAMMA; IMMUNE-RESPONSES; INTERFERON-GAMMA; CHRONIC INFECTION; LEISHMANIA-MAJOR; TARGET-CELLS; MICE AB To investigate early immune responses to the intracellular parasite Toxoplasma gondii, we examined the capacity of nonimmune splenocytes to respond in vitro to intact tachyzoites and soluble tachyzoite antigen (Ag). Both types of stimuli induced high levels of proliferation as well as interferon gamma (IFN-gamma) secretion. Based on several key criteria, the response appeared to be driven by a superantigen present in the parasite. Thus, stimulation of C57BL/6 spleen cells with T. gondii resulted in a preferential threefold expansion of a T cell population expressing the V beta 5 chain of the T cell receptor, and a survey of different inbred mouse strains revealed an inverse correlation between Ag-induced proliferation and genetic deletion of V beta 5. Moreover, proliferation was induced using irradiated Ag-pulsed and infected splenic adherent cells, and was blocked by a major histocompatibility complex class II-specific monoclonal antibody. Furthermore, paraformaldehyde-fixed IA(b)-, IA(k)-, and IE(k)-transfected fibroblast lines were able to specifically bind T. gondii Ag and drive proliferation of T lymphocytes, demonstrating that the response can be mediated by allogeneic class II molecules, and that it does not require cellular Ag processing. It is interesting to note that after 1 wk of culture with Ag, up to 70% of the expanded V beta 5-expressing cells were CD8(+). These results provide the first description of a superantigen activity in a protozoan pathogen. In the case of T. gondii, superantigen-driven expansion of IFN-gamma-secreting CD8(+) lymphocytes may play a role in the development of the dominant IFN-gamma - dependent, cell-mediated immunity characteristic of infection with this parasite. RP DENKERS, EY (reprint author), NIAID, PARASIT DIS LAB, IMMUNOL & CELL BIOL SECT, BLDG 4, ROOM 126, BETHESDA, MD 20892 USA. NR 45 TC 85 Z9 87 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0022-1007 EI 1540-9538 J9 J EXP MED JI J. Exp. Med. PD SEP 1 PY 1994 VL 180 IS 3 BP 985 EP 994 DI 10.1084/jem.180.3.985 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA PC938 UT WOS:A1994PC93800021 PM 8064244 ER PT J AU GRZEGORZEWSKI, K RUSCETTI, FW USUI, N DAMIA, G LONGO, DL CARLINO, JA KELLER, JR WILTROUT, RH AF GRZEGORZEWSKI, K RUSCETTI, FW USUI, N DAMIA, G LONGO, DL CARLINO, JA KELLER, JR WILTROUT, RH TI RECOMBINANT TRANSFORMING GROWTH-FACTOR BETA(1) AND BETA(2) PROTECT MICE FROM ACUTELY LETHAL DOSES OF 5-FLUOROURACIL AND DOXORUBICIN SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HEMATOPOIETIC STEM-CELLS; COLONY-STIMULATING FACTOR; TUMOR-BEARING MICE; TGF-BETA; PROGENITOR CELLS; BONE-MARROW; PROLIFERATION; FACTOR-BETA-1; INVITRO; DEATH AB Transforming growth factor beta(1) (TGF-beta(1)) and TGF-beta(2) can reversibly inhibit the proliferation of hematopoietic progenitor cells in vivo, leading us to hypothesize that such quiescent progenitors might be more resistant to high doses of cell cycle active chemotherapeutic drugs, thereby allowing dose intensification of such agents. Initial studies showed that whereas administration of TGF-beta(1) or TGF-beta(2) did not prevent death in normal mice treated with high doses of 5-fluorouracil (5-FU), those mice that received TGF-beta(2) did exhibit the beginning of a hematologic recovery by day 11 after administration of 5-FU, and were preferentially rescued by a suboptimal number of transplanted bone marrow cells. Subsequently, it was found that the administration of TGF-beta(2) protected recovering progenitor cells from high concentrations of 5-FU in vitro. This protection coincided with the finding that significantly more progenitors for colony-forming unit-culture (CFU-c) and CFU-granulocyte, erythroid, megakaryocyte, macrophage (GEMM) were removed from S-phase by TGF-beta in mice undergoing hematopoietic recovery than in normal mice. Further studies showed that the administration of TGF-beta protected up to 90% of these mice undergoing hematologic recovery from a rechallenge in vivo with high dose 5-FU, while survival in mice not given TGF-beta was <40% Pretreatment of mice with TGF-beta(1) or TGF-beta(2) also protected 70-80% of mice from lethal doses of the noncycle active chemotherapeutic drug, doxorubicin hydrochloride (DXR). These results demonstrate that TGF-beta can protect mice from both the lethal hematopoietic toxicity of 5-FU, as well as the nonhematopoietic toxicity of DXR. This report thus shows that a negative regulator of hematopoiesis can be successfully used systemically to mediate chemoprotection in vivo. C1 NCI,FREDERICK CANC RES & DEV CTR,LEUKOCYTE BIOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. CELTRIX PHARMACEUT INC,SANTA CLARA,CA 95054. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. NR 52 TC 50 Z9 52 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 1 PY 1994 VL 180 IS 3 BP 1047 EP 1057 DI 10.1084/jem.180.3.1047 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA PC938 UT WOS:A1994PC93800027 PM 8064224 ER PT J AU LANTZ, O BENDELAC, A AF LANTZ, O BENDELAC, A TI AN INVARIANT T-CELL RECEPTOR-ALPHA CHAIN IS USED BY A UNIQUE SUBSET OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I-SPECIFIC CD4+ AND CD4-8- T-CELLS IN MICE AND HUMANS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID JUNCTIONAL SEQUENCE; ALLELIC EXCLUSION; THYMIC SELECTION; DEFICIENT MICE; BINDING-SITE; TCR-ALPHA; ANTIGEN; EXPRESSION; GENE; CD4+ AB The mouse thymus contains a mature T cell subset that is distinguishable from the mainstream thymocytes by several characteristics. It is restricted in its usage of T cell receptor (TCR) VP genes to V(beta)8, V(beta)7, and V(beta)2. Its surface phenotype is that of activated/memory cells. It carries the natural killer NK1.1 surface marker. Furthermore, though it consists entirely of CD4(+) and CD4(-)8(-) cells, its selection in the thymus depends solely upon major histocompatibility complex (MHC) class I expression by cells of hematopoietic origin. Forced persistence of CD8, in fact, imparts negative selection. Here, we have studied the TCR repertoire of this subset and found that, whereas the beta chain V-D-J junctions are quite variable, a single invariant ct chain V(alpha)14-J281 is used by a majority of the TCRs. This surprisingly restricted usage of the V(alpha)14-J281 a! chain is dependent on MHC class I expression, but independent of the MHC haplotype. In humans, a similar unusual population including CD4(-)8(-) cells can also be found that uses a strikingly homologous, invariant alpha chain V(alpha)24-JQ. Thus, this unique V-alpha-J(alpha) combination has been conserved in both species, conferring specificity to some shared nonpolymorphic MHC class I/peptide self-ligand(s). This implies that the T cell subset that it defines has a specialized and important role, perhaps related to its unique ability to secrete a large set of lymphokines including interleukin 4, upon primary stimulation in vitro and in vivo. C1 NIAID,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892. RI Lantz, Olivier/J-4960-2012 OI Lantz, Olivier/0000-0003-3161-7719 NR 44 TC 790 Z9 796 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 1 PY 1994 VL 180 IS 3 BP 1097 EP 1106 DI 10.1084/jem.180.3.1097 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA PC938 UT WOS:A1994PC93800032 PM 7520467 ER PT J AU ROMAGNOLI, P GERMAIN, RN AF ROMAGNOLI, P GERMAIN, RN TI THE CLIP REGION OF INVARIANT CHAIN PLAYS A CRITICAL ROLE IN REGULATING MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II FOLDING, TRANSPORT, AND PEPTIDE OCCUPANCY SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HLA-DR MOLECULES; ANTIGEN-PROCESSING MUTANT; SURFACE EXPRESSION; MHC MOLECULES; MICE LACKING; ASSOCIATION; SEQUENCE; BINDING; GENE; GLYCOPROTEINS AB Invariant chain (Ii) contributes in a number of distinct ways to the proper functioning of major histocompatibility complex (MHC) class II molecules. These include promoting effective association and folding of newly synthesized MHC class II alpha and beta subunits, increasing transit of assembled heterodimers out of the endoplasmic reticulum (ER), inhibiting class II peptide binding, and facilitating class II movement to or accumulation in endosomes/lysosomes. Although the cytoplasmic tail of Ii makes a key contribution to the endocytic localization of class II, the relationship between the structure of Ii and its other diverse functions remains unknown. We show here that two thirds of the lumenal segment of Ii can be eliminated without affecting its contributions to the secretory pathway events of class II folding, ER to Golgi transport, or inhibition of peptide binding. These same experiments reveal that a short (25 residue) contiguous internal segment of Ii (the CLIP region), frequently found associated with purified MHC class II molecules, is critical for all three functions. Together with other recent findings, these results raise the possibility that the contributions of Ii to the early postsynthetic behavior of class II may depend on its interaction with the class II binding site. This would be consistent with the intracellular behavior of unoccupied MHC class I and class II molecules as incompletely folded proteins and imply a related structural basis for the similar contributions of Ii to class II and of short peptides to class I assembly and transport. C1 NIAID,IMMUNOL LAB,LYMPHOCYTE BIOL SECT,BETHESDA,MD 20892. RI Romagnoli, Paola/K-2237-2014 NR 40 TC 164 Z9 168 U1 2 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 1 PY 1994 VL 180 IS 3 BP 1107 EP 1113 DI 10.1084/jem.180.3.1107 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA PC938 UT WOS:A1994PC93800033 PM 8064228 ER PT J AU ARYA, SK MOHR, JR AF ARYA, SK MOHR, JR TI CONDITIONAL REGULATORY ELEMENTS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-2 LONG TERMINAL REPEAT SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID CELL ACTIVATION SIGNALS; HIV-2 GENE-EXPRESSION; T-CELLS; TRANSCRIPTIONAL INITIATION; TRANSACTIVATOR TAT; TRANS-ACTIVATOR; HTLV-III; PROMOTER; RETROVIRUSES; STIMULATION AB Mutational analysis of the human immunodeficiency virus type 2 (HIV-2) long terminal repeat (LTR) revealed a novel cis-acting positive and a negative regulatory element in the U3 region, located upstream of the enhancer-promoter region. These elements acted in a cell type-specific manner, being most active in human lymphocytic CEM cells, more active in Jurkat cells than in human monocytic U937 cells and least active in epithelioid HeLa cells. The down-modulatory effect of the negative regulatory element was abolished by HIV-2 Tat, suggesting the involvement of upstream DNA elements in optimal Tat-mediated trans-activation. The sequence elements that respond to T cell activation signals were also located in the upstream U3 region. Notably, the magnitude of the effect of the upstream regulatory elements depended on the basal activity of the LTR, which was also cell type-dependent. This emphasizes the importance of the cell-specific transcriptional factors and other effecters in regulating HIV gene expression. These observations may be relevant to the cell type-specific restriction of virus replication in vivo. RP ARYA, SK (reprint author), NCI,TUMOR CELL BIOL LAB,BLDG 37,BETHESDA,MD 20892, USA. NR 37 TC 3 Z9 3 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD SEP PY 1994 VL 75 BP 2253 EP 2260 DI 10.1099/0022-1317-75-9-2253 PN 9 PG 8 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA PF543 UT WOS:A1994PF54300014 PM 8077923 ER PT J AU MEZEY, E HOFFMAN, BJ HARTA, G PALKOVITS, M NORTHUP, J AF MEZEY, E HOFFMAN, BJ HARTA, G PALKOVITS, M NORTHUP, J TI POTENTIAL PROBLEMS IN USING [S-35] DATP-TAILED OLIGONUCLEOTIDES FOR DETECTING MESSENGER-RNAS IN CERTAIN CELLS OF THE IMMUNE-SYSTEM SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Note DE SIGNAL AMPLIFICATION; S-35 LABELED OLIGONUCLEOTIDES; IN SITU HYBRIDIZATION HISTOCHEMISTRY; HISTAMINE H-2 RECEPTOR ID EXPRESSION; CLONING; GENE AB In this study we examined the cause of unusually intense signals obtained in immune cells by in situ hybridization histochemistry using S-35-labeled oligonucleotides. We verified that the phenomenon is an amplification of a specific signal due to a series of chemical interactions after the probe binds to a specific mRNA in the tissue. The presence of oxidative enzymes in the tissue seems to be necessary for this reaction to occur. Therefore, most cells of the immune system (e.g., macrophages, neutrophil and eosinophil leukocytes), being rich in oxidative enzymes, will show some signal amplification. The intensification of the signal can be avoided if MgCl2 is substituted for CoCl2 in the synthesis of [S-35]-thiophosphate-labeled probes, if 2,3-dimercaptopropanol [British anti-Lewisite (BAL)] is added to the hybridization buffer, or if [P-33]-phosphate is used instead of [S-35]-thiophosphate in the labeling of the probes. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. SEMMELWEIS UNIV MED,SCH MED,DEPT ANAT 1,H-1085 BUDAPEST,HUNGARY. RP MEZEY, E (reprint author), NINCDS,CLIN SCI LAB,BLDG 36,RM 3A17,BETHESDA,MD 20892, USA. RI Palkovits, Miklos/F-2707-2013 NR 16 TC 2 Z9 2 U1 0 U2 0 PU HISTOCHEMICAL SOC INC PI NEW YORK PA MT SINAI MEDICAL CENTER 19 EAST 98TH ST SUTIE 9G, NEW YORK, NY 10029 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD SEP PY 1994 VL 42 IS 9 BP 1277 EP 1283 PG 7 WC Cell Biology SC Cell Biology GA PC632 UT WOS:A1994PC63200011 PM 8064135 ER PT J AU CHRIST, M MCCARTNEYFRANCIS, NL KULKARNI, AB WARD, JM MIZEL, DE MACKALL, CL GRESS, RE HINES, KL TIAN, HS KARLSSON, S WAHL, SM AF CHRIST, M MCCARTNEYFRANCIS, NL KULKARNI, AB WARD, JM MIZEL, DE MACKALL, CL GRESS, RE HINES, KL TIAN, HS KARLSSON, S WAHL, SM TI IMMUNE DYSREGULATION IN TGF-BETA-1-DEFICIENT MICE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; TGF-BETA; T-CELLS; DIFFERENTIATION ANTIGENS; RECEPTOR EXPRESSION; LYMPHOCYTE-B; FACTOR-BETA-1; PROLIFERATION; INTERLEUKIN-2; STIMULATION AB Approximately 2 wk after birth, mice having a TGF-beta 1 null mutation (TGF-beta 1(-/-)) exhibit a progressive wasting syndrome and death. Associated with this phenotype is a multifocal infiltration of lymphocytes and macrophages into targeted organs, especially the heart, lungs, and salivary glands. To explore the consequences of TGF-beta 1 deficiency on the immune system, lymphocyte phenotype and function were analyzed. Initially, lymphoid organ architecture seemed to be normal and, as symptoms developed, the thymus decreased in size, whereas lymph nodes were enlarged. Phenotypically, the TGF-beta 1(-/-) lymphoid cells seemed to be more differentiated in the thymus and activated in the lymph nodes, but remarkably unaffected in the spleen. Moreover, TGF-beta 1(-/-) spleen and lymph nodes displayed enhanced numbers of proliferating cells, as measured by proliferating cell nuclear Ag and/or cyclin-dependent kinase levels. Consistent with this hyperproliferative response, constitutive levels of IL-2 mRNA were elevated in the thymus and both IL-2 and IL-2R mRNA were increased in the lymph nodes. In contrast with the activation profile of TGF-beta 1(-/-) lymphoid cells in vivo, mitogen challenge of these cells in vitro revealed suppressed proliferation that was associated with a defect in inducible IL-2 mRNA expression and IL-2 secretion. Moreover, the addition of rIL-2 restored the deficient mitogen-induced proliferation. The mechanism leading to T cell anergy remains unclear; however, these data confirm the essential role for TGF-beta 1 in maintaining normal immune function. C1 NIDR,IMMUNOL LAB,CELLULAR IMMUNOL SECT,BETHESDA,MD 20892. NINCDS,DEV & METAB NEUROL BRANCH,MOLEC & MED GENET SECT,BETHESDA,MD 20892. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NCI,OFF LAB ANIM SCI,VET & TUMOR PATHOL SECT,FREDERICK,MD 21702. NR 49 TC 184 Z9 188 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 SEP 1 PY 1994 VL 153 IS 5 BP 1936 EP 1946 PG 11 WC Immunology SC Immunology GA PD075 UT WOS:A1994PD07500003 PM 8051399 ER PT J AU PETRAK, D MEMON, SA BIRRER, MJ ASHWELL, JD ZACHARCHUK, CM AF PETRAK, D MEMON, SA BIRRER, MJ ASHWELL, JD ZACHARCHUK, CM TI DOMINANT-NEGATIVE MUTANT OF C-JUN INHIBITS NF-AT TRANSCRIPTIONAL ACTIVITY AND PREVENTS IL-2 GENE-TRANSCRIPTION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-KINASE-C; T-CELL ACTIVATION; DNA-BINDING; INTERLEUKIN-2 PROMOTER; ANTIGEN RECEPTOR; CYCLOSPORINE-A; LYMPHOCYTES-T; LINE JURKAT; FOS JUN; AP-1 AB Expression of the transcription complex AP-1, composed of Jun and Fos family members, can be induced by a variety of stimuli. In lymphocytes, AP-1 transcriptional activity increases after TCR ligation and plays an important role in T cell activation events such as lymphokine secretion. To explore the requirements for AP-1 in IL-2 production, the AP-1 complex was targeted with a dominant negative mutant c-Jun protein, TAM-67, from which the transactivation domain has been deleted. In transient transfections of Jurkat cells, TAM-67 efficiently inhibited endogenous AP-1 transcriptional activity and blocked the activity of a reporter construct containing the 5' regulatory region of the IL-2 gene. TAM-67 also inhibited the transcriptional activity of nuclear factor-AT (NF-AT), whereas the NF-kappa B, NF-IL-2A, and the proximal TRE-like sites were relatively unaffected. The use of this dominant negative transcription factor suggests that: 1) transactivation-defective nuclear factors represent a novel approach to study the functional consequences of nuclear protein interactions on gene transcription; 2) the proximal TRE-like site from the IL-2 promoter is different from the consensus TRE; and 3) AP-1 plays an important role in the transcriptional activation mediated by the NF-AT binding complex. C1 NCI,BIOL RESPONSE MODIFIERS PROGRAM,IMMUNE CELL BIOL LAB,BETHESDA,MD 20892. NCI,DIV CANC PREVENT & CONTROL,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD 20850. RI Memon, Sarfraz/E-1198-2013 NR 39 TC 80 Z9 80 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 SEP 1 PY 1994 VL 153 IS 5 BP 2046 EP 2051 PG 6 WC Immunology SC Immunology GA PD075 UT WOS:A1994PD07500016 PM 8051409 ER PT J AU QUAKYI, IA CURRIER, J FELL, A TAYLOR, DW ROBERTS, T HOUGHTEN, RA ENGLAND, RD BERZOFSKY, JA MILLER, LH GOOD, MF AF QUAKYI, IA CURRIER, J FELL, A TAYLOR, DW ROBERTS, T HOUGHTEN, RA ENGLAND, RD BERZOFSKY, JA MILLER, LH GOOD, MF TI ANALYSIS OF HUMAN T-CELL CLONES SPECIFIC FOR CONSERVED PEPTIDE SEQUENCES WITHIN MALARIA PROTEINS - PAUCITY OF CLONES RESPONSIVE TO INTACT PARASITES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FALCIPARUM CIRCUMSPOROZOITE PROTEIN; MEROZOITE SURFACE-ANTIGEN; CYTOTOXIC LYMPHOCYTES-T; BLOOD STAGE ANTIGEN; PLASMODIUM-FALCIPARUM; EPITOPE; GENE; VACCINE; MICE; MACROPHAGES AB T cells are thought to be of central importance in malaria immunity. Peptides copying malaria protein sequences often stimulate human CD4(+) T cells and it was thought that they represented T cell epitopes present in the parasite and may thus have particular relevance to malaria vaccine development. To verify whether synthetic peptides representing highly conserved regions of parasite Ags may contribute to a malaria vaccine, we searched the data bank for conserved regions of Plasmodium falciparum malaria proteins that were not homologous to known self (human) proteins. We synthesized 24 such peptides representing 11 of the cloned and sequenced malaria asexual stage Ags, which were predicted by algorithms to represent T cell epitopes, and 6 peptides not predicted to be T cell epitopes and used these to generate T cell clones from individuals with an extensive previous history of malaria exposure. The T cell clones responded vigorously to many peptides but only a single clone, specific for a peptide within merozoite surface protein-1, 20-39, VTHESYQELVKKLEALEDAV, and not previously defined to be a T cell epitope responded to malaria parasites by proliferation and secretion of IFN-gamma. This epitope was not revealed by studying parasite-induced T cell lines and is thus subdominant. The clone was able to significantly inhibit parasite growth in vitro. The final step in the inhibition of parasite growth appears to be nonspecific because other activated clones (not specific for malaria sequences) can inhibit parasite growth. Our data suggest that few conserved peptides within malaria parasites can be processed from the intact parasite. However, such peptides that can be processed from malaria parasites may be expected to stimulate parasite-specific T cells that could inhibit parasite growth and as such may be lead candidates for a vaccine aimed at inducing cellular immunity to malaria. C1 QUEENSLAND INST MED RES,MALARIA & ARBOVIRUS UNIT,BRISBANE,QLD 4029,AUSTRALIA. GEORGETOWN UNIV,DEPT BIOL,WASHINGTON,DC 20057. TORREY PINES INST MOLEC STUDIES,SAN DIEGO,CA 92121. NIAID,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. NR 49 TC 34 Z9 34 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1994 VL 153 IS 5 BP 2082 EP 2092 PG 11 WC Immunology SC Immunology GA PD075 UT WOS:A1994PD07500020 PM 8051413 ER PT J AU MEKORI, YA METCALFE, DD AF MEKORI, YA METCALFE, DD TI TRANSFORMING GROWTH-FACTOR-BETA PREVENTS STEM-CELL FACTOR-MEDIATED RESCUE OF MAST-CELLS FROM APOPTOSIS AFTER IL-3 DEPRIVATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID C-KIT LIGAND; BONE-MARROW; TGF-BETA; DEATH APOPTOSIS; HUMAN EOSINOPHILS; MESSENGER-RNA; FACTOR-ALPHA; LINE U937; B-CELLS; FACTOR-BETA-1 AB IL-3-dependent mast cells undergo apoptosis upon removal of IL-3, an event that is prevented by the addition of stem cell factor (SCF) acting through its receptor c-kit, suggesting that SCF provides a mechanism to allow mast cells to survive and to differentiate in tissues in the relative absence of IL-3. This observation is consistent with the thesis that the microenvironment, in part, controls mast cell number and viability by modulating SCF production and release. The purpose of the present study was to determine whether a second factor, TCF-beta 1, was capable of modifying the SCF-mediated survival pathway. TGF-beta 1 (1 and 10 ng/ml), known to be an important regulator of cell growth and function, did inhibit the SCF-mediated rescue from apoptosis in IL-3-deprived mast cells. TGF-beta 1 exerted its inhibitory effect on SCF-mediated rescue from apoptosis, even when added 4 h after the addition of SCF. In contrast, TGF-beta 1 had no substantial effect on the viability of mast cells that were grown in the presence of IL-3. TGF-beta 1 also had no noticeable effect on viability and proliferation of a growth factor-independent mast cell line. The inhibitory effect of TCF-beta 1 was neutralized by specific anti-TGF-beta mAb. TGF-beta 1 did not affect the expression of c-kit, as determined by using flow cytometric analysis of mast cells labeled with FITC-conjugated anti-c-kit. These results demonstrate how SCF and TGF-beta may act in concert to regulate mast cell numbers under physiologic or pathologic conditions. C1 NIAID, ALLERG DIS SECT, CLIN INVEST LAB, BETHESDA, MD 20892 USA. TEL AVIV UNIV, SACKLER SCH MED, IL-69978 TEL AVIV, ISRAEL. MEIR HOSP KFAR SABA, DEPT MED, KEFAR SAVA, ISRAEL. NR 63 TC 59 Z9 59 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1994 VL 153 IS 5 BP 2194 EP 2203 PG 10 WC Immunology SC Immunology GA PD075 UT WOS:A1994PD07500032 PM 7519644 ER PT J AU BRYAN, JP TSAREV, SA IQBAL, M TICEHURST, J EMERSON, S AHMED, A DUNCAN, J RAFIQUI, AR MALIK, IA PURCELL, RH LEGTERS, LJ AF BRYAN, JP TSAREV, SA IQBAL, M TICEHURST, J EMERSON, S AHMED, A DUNCAN, J RAFIQUI, AR MALIK, IA PURCELL, RH LEGTERS, LJ TI EPIDEMIC HEPATITIS-E IN PAKISTAN - PATTERNS OF SEROLOGIC RESPONSE AND EVIDENCE THAT ANTIBODY TO HEPATITIS-E VIRUS PROTECTS AGAINST DISEASE SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; NON-B-HEPATITIS; TRANSMITTED NON-A; MONOCLONAL-ANTIBODIES; IDENTIFICATION; INFECTION; OUTBREAK; SEROTYPE; ELISA AB IgM and IgG anti-hepatitis E virus (HEV) patterns were determined in sera collected during a hepatitis outbreak in Pakistan. HEV infection was detected serologically in 122 patients. IgM anti-HEV was detected in specimens collected up to 2 weeks before and 5-7 weeks after hospitalization in 91% and 100%, respectively, of 122 HEV-infected patients. IgG followed a similar pattern. Peak antibody titers appeared 2-4 weeks after hospitalization. At 20 months after hospitalization, IgM anti-HEV was not detected in any of 33 patients; IgG was found in all. Ige anti-HEV appeared to be protective in contacts of patients. This study confirms HEV as the cause of the outbreak, quantifies IgM and IgG anti-HEV responses, provides evidence that Ige anti-HEV protects against hepatitis E, and demonstrates that Ige anti-HEV persists, but at diminished titer, after infection. Hepatitis E in young adults is the result of primary infection with HEV and, if reinfection occurs, it does not commonly cause serious illness. C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. PAKISTAN US LAB SEROEPIDEMIOL,RAWALPINDI,PAKISTAN. WALTER REED ARMY INST RES,DEPT VIRUS DIS,WASHINGTON,DC. RP BRYAN, JP (reprint author), UNIFORMED SERV UNIV HLTH SCI,DEPT PREVENT MED & BIOMETR,BETHESDA,MD 20814, USA. RI Ticehurst, John/I-7532-2012 NR 20 TC 111 Z9 114 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1994 VL 170 IS 3 BP 517 EP 521 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PE265 UT WOS:A1994PE26500003 PM 8077708 ER PT J AU LEW, JF KAPIKIAN, AZ VALDESUSO, J GREEN, KY AF LEW, JF KAPIKIAN, AZ VALDESUSO, J GREEN, KY TI MOLECULAR CHARACTERIZATION OF HAWAII VIRUS AND OTHER NORWALK-LIKE VIRUSES - EVIDENCE FOR GENETIC-POLYMORPHISM AMONG HUMAN CALICIVIRUSES SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNE ELECTRON-MICROSCOPY; NUCLEOTIDE-SEQUENCE; GASTROENTERITIS; ORGANIZATION; GENOME AB Hawaii virus (HV), from a 1971 family outbreak of gastroenteritis, is serotypically distinct from Norwalk virus (NV), recently identified as a human calicivirus by molecular analysis. About 2600 consecutive nucleotides of the HV genome (including those encoding the viral capsid protein) and part of the polymerase region of three other viruses (MDV1, MDV6, and SV7) were sequenced. Comparison of the amino acid sequence of the capsid protein of HV with NV and other human caliciviruses (Toronto virus [TV24], Desert Shield virus [DSV395], and Southampton virus [SHV]) demonstrated the existence of two major genetic groups (genogroups) typified by HV and NV. HV had 76% identity with TV24 and 48% identity with NV, DSV395, or SHV. In addition, comparison of part of the polymerase protein of HV with other human caliciviruses also showed that there were these two genogroups. The large genetic diversity between the capsid sequence of HV and NV is consistent with their serotypic distinctiveness. RP LEW, JF (reprint author), NIAID,INFECT DIS LAB,BLDG 7,ROOM 129,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 17 TC 112 Z9 113 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1994 VL 170 IS 3 BP 535 EP 542 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PE265 UT WOS:A1994PE26500006 PM 8077710 ER PT J AU LIN, HJ MYERS, LE YENLIEBERMAN, B HOLLINGER, FB HENRARD, D HOOPER, CJ KOKKA, R KWOK, S RASHEED, S VAHEY, M WINTERS, MA MCQUAY, LJ NARA, PL REICHELDERFER, P COOMBS, RW JACKSON, JB AF LIN, HJ MYERS, LE YENLIEBERMAN, B HOLLINGER, FB HENRARD, D HOOPER, CJ KOKKA, R KWOK, S RASHEED, S VAHEY, M WINTERS, MA MCQUAY, LJ NARA, PL REICHELDERFER, P COOMBS, RW JACKSON, JB TI MULTICENTER EVALUATION OF QUANTIFICATION METHODS FOR PLASMA HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 RNA SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID POLYMERASE CHAIN-REACTION; HIV-INFECTED INDIVIDUALS; CLINICAL-TRIALS GROUP; REVERSE-TRANSCRIPTASE; COMBINATION THERAPY; VIREMIA; ZIDOVUDINE; ANTIGEN; VIRIONS; ASSAY AB Six procedures for quantifying plasma human immunodeficiency virus type 1 (HIV-1) RNA were evaluated by nine laboratories. The procedures differed in their sample volume and preparation of samples and methods of amplification and detection. Coded samples in a 10-fold dilution series of HIV-1-spiked plasma were correctly ranked by all six procedures. Subsequently, coded duplicate plasma samples from 16 HIV-1-infected patients were tested using a common set of standards. Several HIV-1 RNA procedures were sufficiently reproducible so that an empiric 4-fold change could be viewed as significant. HIV-1 RNA levels in the patients (up to 370,000 RNA copies/mL) correlated with proviral HIV-1 DNA and were inversely correlated with CD4 cell counts; HIV-1 RNA assays were more sensitive than plasma viremia, standard p24 antigen, or immune complex-dissociated p24 antigen assays. This study demonstrated that several HIV-1 RNA quantitative assays are ready for use in clinical trials. C1 CASE WESTERN RESERVE UNIV,INST PATHOL,CLEVELAND,OH 44106. BAYLOR COLL MED,DIV MOLEC VIROL,HOUSTON,TX 77030. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. UNIV CLEVELAND HOSP,CLEVELAND CLIN FDN,DEPT PATHOL,CLEVELAND,OH 44106. ABBOTT LABS,ABBOTT PK,IL 60064. UNIV WASHINGTON,RETROVIRUS LAB,SEATTLE,WA 98195. CHIRON CORP,EMERYVILLE,CA 94608. ROCHE MOLEC SYST,ALAMEDA,CA. UNIV SO CALIF,SCH MED,VIRAL ONCOL & AIDS RES LAB,LOS ANGELES,CA. STANFORD UNIV,SCH MED,CTR AIDS RES,PALO ALTO,CA 94304. WALTER REED ARMY INST RES,DIV RETROVIROL,ROCKVILLE,MD. NIAID,DIV AIDS,ROCKVILLE,MD. NCI,TUMOR CELL BIOL LAB,VIRUS BIOL SECT,FREDERICK,MD 21701. FU NIAID NIH HHS [AI-25879, AI-82517, AI-27664] NR 29 TC 141 Z9 142 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1994 VL 170 IS 3 BP 553 EP 562 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PE265 UT WOS:A1994PE26500008 PM 7915748 ER PT J AU KRESINA, TF WISNEWSKI, A LOVEHOMAN, L RAMIREZ, B NEIL, GA AF KRESINA, TF WISNEWSKI, A LOVEHOMAN, L RAMIREZ, B NEIL, GA TI INDUCTION OF HEPATIC PATHOLOGY IN SCID-HU MICE ENGRAFTED WITH PERIPHERAL-BLOOD LYMPHOCYTES OF PATIENTS WITH SCHISTOSOMIASIS-JAPONICA SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID GRANULOMA-FORMATION; MONONUCLEAR-CELLS; FIBROSIS; IL-2 AB SCID mice were engrafted with peripheral blood lymphocytes (PBL) derived from persons currently or previously infected with Schistosoma japonicum. After immunization with soluble worm antigenic preparation, the SCID-Hu mice were analyzed for a human immune response. ELISA revealed a low titer of human antibody recognizing soluble egg antigens in 2 of 10 mice. One mouse had detectable levels of interleukin (IL)-2 and gamma-interferon, TH1 phenotype cytokines. All mice had elevated levels of IL-4, a TH2 phenotype cytokine. The human cytokine profile of the mice paralleled the patient's serum profile at clinical examination. In addition, all mice had substantial hepatic pathology, including inflammatory cell infiltrates and macrovesicular fat deposition. The data indicate that activation of PBL from patients with a history of schistosomiasis japonica infection can result in focal hepatic pathology, which may be driven by specific cytokines. C1 UNIV IOWA,SCH MED,IOWA CITY,IA 52242. NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02215. RES INST TROP MED,MANILA,PHILIPPINES. ASTRA MERCK,WAYNE,PA. RP KRESINA, TF (reprint author), NIDDK,WESTWOOD BLDG,ROOM 3A17,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [AI-30601, AI-29102] NR 15 TC 2 Z9 2 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1994 VL 170 IS 3 BP 733 EP 736 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PE265 UT WOS:A1994PE26500041 PM 8077739 ER PT J AU MCCARTHY, JS OTTESEN, EA NUTMAN, TB AF MCCARTHY, JS OTTESEN, EA NUTMAN, TB TI ONCHOCERCIASIS IN ENDEMIC AND NONENDEMIC POPULATIONS - DIFFERENCES IN CLINICAL PRESENTATION AND IMMUNOLOGICAL FINDINGS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID IVERMECTIN; HUMANS AB To characterize the clinical and laboratory features of onchocerciasis in visitors to endemic areas and to compare them with those seen in endemic subjects, 20 returned visitors and 21 endemic subjects with onchocerciasis were evaluated. Dermatitis was the most frequent clinical finding among the returned visitors. None had nodules or eye disease and, in contrast to the endemic subjects, microfiladermia was often absent or of low density. All persons studied had antibody responses measurable by ELISA to both soluble Onchocerca volvulus antigen and a panel of diagnostic recombinant antigens. Eosinophil and IgE levels were significantly higher in the endemic group, as was the capacity of peripheral blood mononuclear cells from this group to produce the T helper cell-like cytokines interleukin-4 and -5. It is likely that the chronicity and intensity of infection in endemic subjects account for the clinical and immunologic differences observed between the 2 groups. RP MCCARTHY, JS (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. NR 15 TC 40 Z9 40 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1994 VL 170 IS 3 BP 736 EP 741 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PE265 UT WOS:A1994PE26500042 PM 8077740 ER PT J AU PETEN, EP STRIKER, LJ AF PETEN, EP STRIKER, LJ TI PROGRESSION OF GLOMERULAR-DISEASES SO JOURNAL OF INTERNAL MEDICINE LA English DT Review ID POLYMERASE CHAIN-REACTION; BOVINE GROWTH-HORMONE; MESSENGER-RNA LEVELS; TRANSGENIC MICE; EXTRACELLULAR-MATRIX; IV COLLAGEN; HUMAN GLOMERULOSCLEROSIS; DIABETIC NEPHROPATHY; COMPETITIVE PCR; RENAL-DISEASE AB The nature and slope of progression of glomerular diseases is the subject of considerable discussion. The use of renal biopsies has been accompanied by considerable improvement in the classification of glomerular disease. However, the clinical and histological tools available to assess prognosis in individual patients lack accuracy, especially in slowly progressive glomerular diseases such as diabetes mellitus. The development of molecular biology tools provides a new approach to the analysis of glomerulosclerosis. The accumulation of extracellular matrix in the glomerulus results from an exaggerated synthesis of collagens and other molecules forming the basement membranes, and is accompanied by an increase in the corresponding mRNAs. The measure of local glomerular gene activation can therefore provide a dynamic view of glomerular scarring. Utilizing a method combining microdissection of the glomeruli, reverse transcription in situ and a competitive polymerase-chain-reaction assay we were able to measure minute amounts of mRNAs in single mouse and human glomeruli. Both in mouse models and in human glomerulosclerosis we found upregulation of basement membrane collagen genes in the glomeruli. The increase appeared to be parallel to the slope of progression of glomerulosclerosis in experimental animals. This new approach may therefore provide a quantitative and sensitive method to define the propensity to sclerosis in human disease. C1 NIDDKD,METAB DIS BRANCH,RENAL CELL BIOL SECT,BETHESDA,MD 20892. NR 39 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD SEP PY 1994 VL 236 IS 3 BP 241 EP 249 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA PE721 UT WOS:A1994PE72100002 PM 8077878 ER PT J AU ADAMS, JR SHEPPARD, CA SHAPIRO, M TOMPKINS, GJ AF ADAMS, JR SHEPPARD, CA SHAPIRO, M TOMPKINS, GJ TI LIGHT AND ELECTRON-MICROSCOPIC INVESTIGATIONS ON THE HISTOPATHOLOGY OF THE MIDGUT OF GYPSY-MOTH LARVAE INFECTED WITH LDMNPV PLUS A FLUORESCENT BRIGHTENER SO JOURNAL OF INVERTEBRATE PATHOLOGY LA English DT Note DE LYMANTRIA DISPAR NUCLEAR POLYHEDROSIS VIRUS; FLUORESCENT BRIGHTENER; HISTOPATHOLOGY; ELECTRON MICROSCOPE; IMMUNOCYTOCHEMISTRY ID NUCLEAR POLYHEDROSIS-VIRUS; OPTICAL BRIGHTENERS; LEPIDOPTERA; BACULOVIRUSES; HOSTS C1 NICHHD,CELLULAR & MOLEC NEUROPHYSIOL LAB,BETHESDA,MD 20892. US EPA,DIV ENVIRONM FATE & EFFECTS,OFF PESTICIDE PROGRAMS,WASHINGTON,DC 20460. RP ADAMS, JR (reprint author), USDA ARS,INSECT BIOCONTROL LAB,BARC-W,BELTSVILLE,MD 20705, USA. NR 10 TC 28 Z9 30 U1 1 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0022-2011 J9 J INVERTEBR PATHOL JI J. Invertebr. Pathol. PD SEP PY 1994 VL 64 IS 2 BP 156 EP 159 DI 10.1006/jipa.1994.1089 PG 4 WC Zoology SC Zoology GA PK180 UT WOS:A1994PK18000016 ER PT J AU JINDO, T TSUBOI, R IMAI, R TAKAMORI, K RUBIN, JS OGAWA, H AF JINDO, T TSUBOI, R IMAI, R TAKAMORI, K RUBIN, JS OGAWA, H TI HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR STIMULATES HAIR-GROWTH OF MOUSE VIBRISSAE IN ORGAN-CULTURE SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE CYTOKINES; FIBROBLAST GROWTH FACTOR; TNF-ALPHA; IL-1-ALPHA ID ANCHORAGE-INDEPENDENT GROWTH; FACTOR SCATTER FACTOR; EPITHELIAL-CELLS; FACTOR RECEPTORS; FOLLICLES; EXPRESSION; SKIN; MOTILITY; MITOGEN; MICE AB Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional polypeptide that acts as a mitogen, motogen, or morphogen, depending on the biologic context. In this study, we examined the effect of HGF/SF on hair growth using a serum-free organ culture system. Vibrissal hair follicles isolated from newborn mice were cultured at 31 degrees C in 95% O-2/5% CO2 for 72 h in the presence of various cytokines or growth factors, and elongation of hair shaft, DNA, and protein synthesis in hair follicles were measured. Among the agents tested, only HGF/SF significantly increased hair follicle length (p < 0.001), H-3-thymidine (p < 0.001), and S-35-cysteine (p < 0.05) incorporation. The effect of HGF/SF was dose dependent, with maximal stimulation obtained at 10 ng/ml. The increase in hair follicle length and thymidine incorporation were specifically inhibited by a neutralizing antibody against HGF/SF. These results indicate that HGF/SF can promote hair growth and may have clinical utility in this regard. C1 JUNTENDO UNIV, SCH MED, DEPT DERMATOL, BUNKYO KU, TOKYO 113, JAPAN. NCI, CELLULAR & MOLEC BIOL LAB, BETHESDA, MD 20892 USA. NR 45 TC 50 Z9 54 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1994 VL 103 IS 3 BP 306 EP 309 DI 10.1111/1523-1747.ep12394731 PG 4 WC Dermatology SC Dermatology GA PG082 UT WOS:A1994PG08200007 PM 8077695 ER PT J AU LIU, L SHACK, S STETLERSTEVENSON, WG HUDGINS, WR SAMID, D AF LIU, L SHACK, S STETLERSTEVENSON, WG HUDGINS, WR SAMID, D TI DIFFERENTIATION OF CULTURED HUMAN-MELANOMA CELLS INDUCED BY THE AROMATIC FATTY-ACIDS PHENYLACETATE AND PHENYLBUTYRATE SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE CYTOSTASIS; INVASION; TUMORIGENICITY; MELANOGENESIS; PROTEOLYSIS ID STIMULATE AUTOLOGOUS LYMPHOCYTES; FETAL HEMOGLOBIN PRODUCTION; CANCER-CELLS; AGENTS; GROWTH; 4-PHENYLBUTYRATE; PREVENTION; INHIBITION; EXPRESSION; INVASION AB The increasing incidence of melanoma and the poor responsiveness of disseminated disease to conventional treatments call for the development of new therapeutic approaches. Phenylacetate, a nontoxic differentiation inducer, can suppress the growth of other neuroectodermal tumors, i.e., gliomas, in laboratory models and in humans. This finding led us to explore the efficacy of phenylacetate and related aromatic fatty acids in melanoma. Phenylacetate and phenylbutyrate were found to a) induce selective cytostasis and maturation of cultured human melanoma cells, b) modulate the expression of genes implicated in tumor metastasis (type IV collagenase and tissue inhibitor of metallo-proteinases-2) and immunogenicity (HLA class I); and c) enhance the efficacy of other agents of clinical interest, including retinoids, interferon-alpha, suramin, and 5-aza-2'-deoxycytidine. Reflecting on the phenotypic heterogeneity of melanoma, the degree of biologic alterations induced by phenylacetate/phenylbutyrate varied significantly among the tumor cell lines tested. Although losing invasive capacity and tumorigenicity in athymic mice, poorly differentiated cells exhibited only a marginal change in morphology, remained amelanotic, and resumed growth after treatment was discontinued. By contrast, treatment of melanoma cells that were in a more advanced state of maturation resulted in profound alterations in cell growth, morphology, and pigmentation consistent with terminal differentiation. The in vitro antitumor activity was observed with nontoxic, pharmacologic concentrations of phenylacetate and phenylbutyrate, suggesting potential clinical use of these drugs in the treatment of melanomas. C1 NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 42 TC 58 Z9 63 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1994 VL 103 IS 3 BP 335 EP 340 DI 10.1111/1523-1747.ep12394874 PG 6 WC Dermatology SC Dermatology GA PG082 UT WOS:A1994PG08200012 PM 8077698 ER PT J AU ROCKEN, M BONOMO, A LEVINE, A SCOTT, D SHEVACH, EM RACKE, M AF ROCKEN, M BONOMO, A LEVINE, A SCOTT, D SHEVACH, EM RACKE, M TI CYTOKINE-MEDIATED IMMUNE DEVIATION AS A THERAPY FOR INFLAMMATORY AUTOIMMUNE-DISEASE SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV MUNICH,MUNICH,GERMANY. NIH,BETHESDA,MD 20892. MONSANTO CO,ST LOUIS,MO. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1994 VL 103 IS 3 BP 434 EP 434 PG 1 WC Dermatology SC Dermatology GA PG082 UT WOS:A1994PG08200246 ER PT J AU FIEBIGER, E MAURER, D HOLUB, H REININGER, B KINET, JP STINGL, G AF FIEBIGER, E MAURER, D HOLUB, H REININGER, B KINET, JP STINGL, G TI AUTOREACTIVITY DIRECTED AGAINST THE ALPHA-CHAIN OF FC-EPSILON-RI IN IGG FRACTIONS OF PATIENTS SUFFERING FROM CHRONIC URTICARIA SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV VIENNA,SCH MED,DEPT DERMATOL,DIAID,VIENNA,AUSTRIA. NIAID,MOLEC ALLERGY & IMMUNOL SECT,ROCKVILLE,MD 20852. NR 0 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1994 VL 103 IS 3 BP 436 EP 436 PG 1 WC Dermatology SC Dermatology GA PG082 UT WOS:A1994PG08200259 ER PT J AU KIRNBAUER, R NONNENMACHER, B HUBBERT, N SHAH, K MUNOZ, N SCHIFFMANN, M BOSCH, X VISCIDI, R LOWY, D SCHILLER, J AF KIRNBAUER, R NONNENMACHER, B HUBBERT, N SHAH, K MUNOZ, N SCHIFFMANN, M BOSCH, X VISCIDI, R LOWY, D SCHILLER, J TI SEROLOGIC RESPONSE TO HPV16 CAPSIDS IN WOMEN IS ASSOCIATED WITH PERSISTENT HPV16 INFECTION AND INCREASED CERVICAL-CANCER RISK SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIH,CELL ONCOL LAB,BETHESDA,MD. UNIV VIENNA,DEPT DERMATOL,DIAID,VIENNA,AUSTRIA. JOHNS HOPKINS UNIV,BALTIMORE,MD. IARC,LYON,FRANCE. NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1994 VL 103 IS 3 BP 436 EP 436 PG 1 WC Dermatology SC Dermatology GA PG082 UT WOS:A1994PG08200262 ER PT J AU MAURER, D FIEBIGER, E REININGER, B EBNER, C KRAFT, D KINET, JP STINGL, G AF MAURER, D FIEBIGER, E REININGER, B EBNER, C KRAFT, D KINET, JP STINGL, G TI IN-VIVO IGE-BINDING TO MONOCYTES OF ATOPICS OCCURS VIA HIGH-AFFINITY RATHER THAN LOW-AFFINITY IGE RECEPTORS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV VIENNA,SCH MED,DEPT DERMATOL,DIAID,VIENNA,AUSTRIA. NIAID,MOLEC ALLERGY & IMMUNOL SECT,ROCKVILLE,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1994 VL 103 IS 3 BP 437 EP 437 PG 1 WC Dermatology SC Dermatology GA PG082 UT WOS:A1994PG08200266 ER PT J AU KARLHOFER, FM HUNZIKER, R MARGULIES, DH YOKOYAMA, WM AF KARLHOFER, FM HUNZIKER, R MARGULIES, DH YOKOYAMA, WM TI MODULATION OF EXPRESSION AND FUNCTION OF A NATURAL-KILLER (NK) CELL-RECEPTOR BY HOST MHC CLASS-I SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 MT SINAI MED CTR,DEPT MED,NEW YORK,NY 10029. NIH,IMMUNOL LAB,BETHESDA,MD. RI Margulies, David/H-7089-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1994 VL 103 IS 3 BP 438 EP 438 PG 1 WC Dermatology SC Dermatology GA PG082 UT WOS:A1994PG08200272 ER PT J AU OSTERHOFF, B KLUBAL, R MAURER, D KINET, JP STINGL, G AF OSTERHOFF, B KLUBAL, R MAURER, D KINET, JP STINGL, G TI THE HIGH-AFFINITY RECEPTOR FOR IGE IS THE BIOLOGICALLY RELEVANT IGE-BINDING STRUCTURE IN ATOPIC-DERMATITIS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV VIENNA,SCH MED,DEPT DERMATOL,DIAID,VIRCC,VIENNA,AUSTRIA. NIAID,MOLEC ALLERGY & IMMUNOL SECT,ROCKVILLE,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1994 VL 103 IS 3 BP 438 EP 438 PG 1 WC Dermatology SC Dermatology GA PG082 UT WOS:A1994PG08200270 ER PT J AU LOWDEN, DA LINDEMANN, GW MERLINO, G BARASH, BD CALVET, JP GATTONE, VH AF LOWDEN, DA LINDEMANN, GW MERLINO, G BARASH, BD CALVET, JP GATTONE, VH TI RENAL CYSTS IN TRANSGENIC MICE EXPRESSING TRANSFORMING GROWTH-FACTOR-ALPHA SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID POLYCYSTIC KIDNEY-DISEASE; GENE-EXPRESSION; FACTOR RECEPTOR; EARLY REGION; TGF-ALPHA; MOUSE; GLAND; CELLS; BETA; RAT AB Transforming growth factor-alpha (TGF-alpha) is a member of the epidermal growth factor (EGF) family of proteins and, like EGF, elicits its cellular function by binding to the EGF receptor. EGF stimulation may have a role in several normal and pathologic processes in the kidney, and EGF has been implicated in the development of renal cysts in vitro and in human autosomal dominant polycystic kidney disease. We sought to determine whether renal expression of an EGF-like protein (TGF-alpha) could lead to the formation of renal cysts in vivo. We examined morphologic alterations to the normal kidney caused by renal expression of a TGF-alpha transgene linked to a mouse metallothionein promoter stably integrated into the genome of the CD1 mouse. TGF-alpha transgene expression was induced with exogenous zinc treatment starting at 4 weeks of age, and mice were killed at 8 weeks of age. The transgene was expressed at higher levels in female transgenic mice than in male transgenic mice. The augmented expression of the TGF-alpha transgene in females was associated with increased renal size and the development of renal epithelial cysts. Both male and female mice exhibited increases in glomerular size and mesangial volume density. These results provide evidence that stimulation by an endogenous EGF-like protein can lead to renal enlargement, glomerular mesangial expansion, and renal cyst formation. C1 UNIV KANSAS,MED CTR,DEPT ANAT & CELL BIOL,KANSAS CITY,KS 66160. UNIV KANSAS,MED CTR,DEPT BIOCHEM & MOLEC BIOL,KANSAS CITY,KS. UNIV KANSAS,KIDNEY & UROL RES CTR,KANSAS CITY,KS. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. FU NIDDK NIH HHS [DK37100] NR 42 TC 75 Z9 77 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD SEP PY 1994 VL 124 IS 3 BP 386 EP 394 PG 9 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA PG170 UT WOS:A1994PG17000019 PM 8083581 ER PT J AU WILFORD, BB FINCH, J CZECHOWICZ, DJ WARREN, D AF WILFORD, BB FINCH, J CZECHOWICZ, DJ WARREN, D TI AN OVERVIEW OF PRESCRIPTION DRUG MISUSE AND ABUSE - DEFINING THE PROBLEM AND SEEKING SOLUTIONS SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Editorial Material C1 DURHAM CTY SUBST ABUSE SERV,RES TRIANGLE PK,NC. N CAROLINA GOVERNORS INST ALCOHOL & SUBST,RES TRIANGLE PK,NC. NIDA,DIV CLIN RES,ROCKVILLE,MD. DUKE UNIV,DIV ENVIRONM & OCCUPAT MED,DURHAM,NC. RP WILFORD, BB (reprint author), GEORGE WASHINGTON UNIV,INTERGOVT HLTH POLICY PROJECT,PHARMACEUT POLICY RES CTR,WASHINGTON,DC, USA. NR 16 TC 13 Z9 13 U1 0 U2 5 PU AMER SOC LAW MEDICINE ETHICS PI BOSTON PA 765 COMMONWEALTH AVE, 16TH FL, BOSTON, MA 02215 SN 0277-8459 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD FAL PY 1994 VL 22 IS 3 BP 197 EP 203 DI 10.1111/j.1748-720X.1994.tb01295.x PG 7 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA QA211 UT WOS:A1994QA21100001 PM 7749473 ER PT J AU MOLINARI, SP COOPER, JR CZECHOWICZ, DJ AF MOLINARI, SP COOPER, JR CZECHOWICZ, DJ TI FEDERAL-REGULATION OF CLINICAL-PRACTICE IN NARCOTIC ADDICTION TREATMENT - PURPOSE, STATUS, AND ALTERNATIVES SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article ID METHADONE-MAINTENANCE RP MOLINARI, SP (reprint author), NIDA,DIV CLIN RES,MED AFFAIRS BRANCH,ROCKVILLE,MD, USA. NR 20 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC LAW MEDICINE ETHICS PI BOSTON PA 765 COMMONWEALTH AVE, 16TH FL, BOSTON, MA 02215 SN 0277-8459 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD FAL PY 1994 VL 22 IS 3 BP 231 EP 239 DI 10.1111/j.1748-720X.1994.tb01300.x PG 9 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA QA211 UT WOS:A1994QA21100006 PM 7749478 ER PT J AU MIKOVITS, JA MEYERS, AM ORTALDO, JR MINTY, A CAPUT, D FERRARA, P RUSCETTI, FW AF MIKOVITS, JA MEYERS, AM ORTALDO, JR MINTY, A CAPUT, D FERRARA, P RUSCETTI, FW TI IL-4 AND IL-13 HAVE OVERLAPPING BUT DISTINCT EFFECTS ON HIV PRODUCTION IN MONOCYTES SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE MONOCYTES; CYTOKINES; HIV REGULATION ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; MONONUCLEAR PHAGOCYTES; INFECTED MONOCYTES; IMMUNE-RESPONSES; IN-VITRO; MACROPHAGES; EXPRESSION; CELLS; TYPE-1 AB In HIV-1-infected monocytes and monocytoid cell lines, viral expression can be observed as high-level production, restricted (chronic low-level) expression, and latency (no viral expression). Interleukin-13 (IL-13) and IL-4, which have remarkedly similar deactivating effects on inflammatory monocyte functions, were studied for their regulation of HIV expression in monocytes. Pretreatment of peripheral monocytes for 48-72 h with IL-13 markedly decreased acute HIV infection, whereas IL-4 increased it. Similar effects were seen when the UI and R-THP-1 monocytoid cell lines with restricted HIV expression were treated with these cytokines. However, when these continuously producing cell lines were chronically treated with cytokines, IL-13 increased HIV production. Neither IL-4 nor IL-13 stimulated HIV expression in latently infected cells. In chronically infected cells, several cytokines reduced viral mRNA. Both IL-4 and IL-13 increased monocyte aggregate formation, but only IL-4 ultimately stimulated cytolysis of HIV-infected monocytes as well as increased apoptosis of U1. In the presence of tumor necrosis factor alpha or IL-6, which upregulate HIV expression, IL-13 could no longer suppress HIV expression. These results indicate that IL-4 and IL-13, although closely related in modulating monocyte function, can have divergent effects on HIV expression in monocytes. Collectively, these data suggest that there exists a complex cytokine tissue environment with positive regulators of HIV expression able to override negative regulators. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BRMP,LLB,FREDERICK,MD 21702. SANOFI ELI BIO RECH,LABEGE,FRANCE. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74102] NR 45 TC 12 Z9 13 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD SEP PY 1994 VL 56 IS 3 BP 340 EP 346 PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA PF341 UT WOS:A1994PF34100019 PM 7916030 ER PT J AU PREVIATO, L GUARDAMAGNA, O DUGI, KA RONAN, R TALLEY, GD SANTAMARINAFOJO, S BREWER, HB AF PREVIATO, L GUARDAMAGNA, O DUGI, KA RONAN, R TALLEY, GD SANTAMARINAFOJO, S BREWER, HB TI A NOVEL MISSENSE MUTATION IN THE C-TERMINAL DOMAIN OF LIPOPROTEIN-LIPASE (GLU(410)-]VAL) LEADS TO ENZYME INACTIVATION AND FAMILIAL CHYLOMICRONEMIA SO JOURNAL OF LIPID RESEARCH LA English DT Article DE APOC-II; HEPATIC LIPASE; PANCREATIC LIPASE; PCR-AMPLIFIED GENOMIC DNA ID SITE-DIRECTED MUTAGENESIS; POLYMERASE CHAIN-REACTION; HUMAN HEPATIC LIPASE; POST-HEPARIN PLASMA; SECONDARY-STRUCTURE; NONSENSE MUTATION; POSTHEPARIN PLASMA; I HYPERLIPIDEMIA; CATALYTIC TRIAD; CHIMERIC LIPASE AB Lipoprotein lipase (LPL) is a complex enzyme consisting of multiple functional domains essential for the initial hydrolysis of triglycerides present in plasma lipoproteins. Previous studies have localized the catalytic domain of LPL, responsible for the hydrolytic function of the enzyme, to the N-terminus whereas the C-terminal end may play a role in lipid and heparin binding. To date, most described missense mutations resulting in a nonfunctional LPL have been located in the N-terminal region of the enzyme. In this manuscript we describe the defect in the LPL gene of a patient with triglycerides ranging from normal to 12,000 mg/dl, low LPL mass, and no LPL activity in postheparin plasma. Sequencing of patient PCR-amplified DNA identified two separate mutations in the C-terminal domain of LPL: an A --> T transversion at nucleotide 1484 resulting in a Glu(410) --> Val substitution and a C --> G mutation at position 1595 that introduces a premature stop codon at position 447. Digestion with MaeIII and MnII established that the patient is a true homozygote for both mutations. In order to investigate the functional significance of these defects, mutant enzymes containing either the Val(410) or the Ter(447) mutations as well as both Val(410) and Ter(447), were expressed in vitro. Compared to the wild-type enzyme, LPL(447) demonstrated a moderate reduction of specific activity using triolein (70% of normal) and tributyrin (74% of normal) substrates, while LPL(410) had a significant (11% and 23% of normal) reduction of the normal lipase and esterase specific activities, respectively. Mutant-LPL(410/447) was virtually inactive using either triolein or tributyrin substrates establishing the functional significance of this combined defect. When analyzed by heparin-Sepharose affinity chromatography, a small fraction of LPL(410), like the native LPL dimer, eluted at an NaCl concentration of 1.3 M and had a normal specific activity. However, most of the LPL(410) mass was detected in an inactive peak that, like the normal LPL-monomer, eluted at 0.8 M NaCl, indicating that the Glu(410) --> Val substitution may alter the stability of the LPL dimer. In summary, we have identified a unique mutation in the C-terminal domain of LPL that significantly affects the function of the mutant enzyme. Despite its location in the C-terminal domain of LPL, this mutation does not directly disrupt the heparin-binding properties of the mutant enzyme or its ability to interact with or hydrolyze either lipid or water-soluble substrates. Instead, the loss of enzyme activity appears to be related to a change in the monomer-dimer equilibrium of the mutant enzyme. Our studies indicate that, in addition to the proposed role in the lipid binding function, the C-terminal domain may play an important role in the formation of the active LPL dimer. C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. UNIV TURIN,DEPT PEDIAT,TURIN,ITALY. NR 45 TC 43 Z9 45 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 SEP PY 1994 VL 35 IS 9 BP 1552 EP 1560 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PG303 UT WOS:A1994PG30300005 PM 7806969 ER PT J AU HORSKA, A HORSKY, J SPENCER, RGS AF HORSKA, A HORSKY, J SPENCER, RGS TI MEASUREMENT OF SPIN-LATTICE RELAXATION-TIMES IN SYSTEMS UNDERGOING CHEMICAL-EXCHANGE SO JOURNAL OF MAGNETIC RESONANCE SERIES A LA English DT Article ID SATURATION TRANSFER MEASUREMENTS; CREATINE-KINASE; RAT-HEART; NMR; KINETICS AB A new method is presented for measuring spin-lattice relaxation times in systems with chemical exchange. The method is based on an analysis of the effect of exchange on saturation factors. Unlike the inversion-recovery method with saturation, our experiment does not require selective excitation; it also does not require a fit of data to a multiple-exponential model, in contrast to inversion recovery without saturation. A number of variations of the experiment are presented, which are applicable to different regimes of T-1 and exchange-rate values. The methods are demonstrated for the creatine kinase reaction in an in vitro sample. (C) 1994 Academic Press, Inc. C1 INST CLIN & EXPTL MED,PRAGUE,CZECH REPUBLIC. ASCR,INST MACROMOLEC CHEM,PRAGUE,CZECH REPUBLIC. RP HORSKA, A (reprint author), NIA,CELL & MOLEC BIOL LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. RI Horsky, Jiri/G-3442-2014 NR 16 TC 24 Z9 24 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1064-1858 J9 J MAGN RESON SER A JI J. Magn. Reson. Ser. A PD SEP PY 1994 VL 110 IS 1 BP 82 EP 89 DI 10.1006/jmra.1994.1185 PG 8 WC Physics, Atomic, Molecular & Chemical SC Physics GA PH364 UT WOS:A1994PH36400014 ER PT J AU MCNELLIS, D AF MCNELLIS, D TI A VIEW FROM BETHESDA - ACCOMPLISHMENTS OF THE MATERNAL-FETAL MEDICINE UNITS (MFMU) NETWORK SO JOURNAL OF MATERNAL-FETAL INVESTIGATION LA English DT Editorial Material RP MCNELLIS, D (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0939-6322 J9 J MATERN-FETAL INVES JI J. Matern.-Fetal Invest. PD FAL PY 1994 VL 4 IS 4 BP 195 EP 196 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA QA772 UT WOS:A1994QA77200001 ER PT J AU HONE, J ACCILI, D ALGAZALI, LI LESTRINGANT, G ORBAN, T TAYLOR, SI AF HONE, J ACCILI, D ALGAZALI, LI LESTRINGANT, G ORBAN, T TAYLOR, SI TI HOMOZYGOSITY FOR A NEW MUTATION (ILE(119)-]MET) IN THE INSULIN-RECEPTOR GENE IN 5 SIBS WITH FAMILIAL INSULIN-RESISTANCE SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID LEPRECHAUNISM; TRANSPORT AB Mutations in the insulin receptor gene can cause genetic syndromes such as leprechaunism that are associated with extreme insulin resistance. We have investigated a patient with leprechaunism born of a consanguineous marriage. All 22 exons of the insulin receptor gene were screened for mutations using denaturing gradient gel electrophoresis. Thereafter, the nucleotide sequences of selected exons were determined directly. The patient was homozygous for a point mutation in exon 2 of the insulin receptor gene which results in the substitution of methionine for isoleucine at codon 119. Thus, the mutant allele encodes a receptor that has a mutation in the putative insulin binding domain. Accordingly, the mutant receptor would be predicted not to transduce the insulin signal effectively. In spite of a homozygous abnormality of the insulin receptor gene and many of the clinical features of severe insulin resistance, the proband's clinical syndrome was noticeably different from previously described patients with leprechaunism who usually die within the first six months of life. There are a total of nine children in the family, five of whom are homozygous for the Ile(119) --> Met mutation in the insulin receptor gene, and are clinically affected with varying degrees of severity. Four unaffected sibs are clinically normal; two are heterozygous carriers of the mutant allele, one is homozygous for the normal allele, and one unaffected sib was not available for molecular studies. C1 NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. UNITED ARAB EMIRATES UNIV,DEPT PEDIAT,AL AIN,U ARAB EMIRATES. TAWAM HOSP,DEPT DERMATOL,AL AIN,U ARAB EMIRATES. TAWAM HOSP,DEPT PEDIAT,AL AIN,U ARAB EMIRATES. NR 10 TC 16 Z9 20 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD SEP PY 1994 VL 31 IS 9 BP 715 EP 716 DI 10.1136/jmg.31.9.715 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA PH479 UT WOS:A1994PH47900012 PM 7815442 ER PT J AU BIESECKER, LG TOPF, K GRAHAM, JM AF BIESECKER, LG TOPF, K GRAHAM, JM TI FAMILIAL PALLISTER-HALL SYNDROME SO JOURNAL OF MEDICAL GENETICS LA English DT Letter C1 PERMANENTE MED GRP INC,SACRAMENTO,CA 95825. CEDARS SINAI MED CTR,DIV CLIN GENET DYSMORPHOL,LOS ANGELES,CA 90048. RP BIESECKER, LG (reprint author), NIH,NATL CTR HUMAN GENOME RES,DEPT HLTH & HUMAN SERV,BETHESDA,MD 20892, USA. NR 4 TC 3 Z9 3 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD SEP PY 1994 VL 31 IS 9 BP 740 EP 740 DI 10.1136/jmg.31.9.740-a PG 1 WC Genetics & Heredity SC Genetics & Heredity GA PH479 UT WOS:A1994PH47900020 PM 7880273 ER PT J AU KULLER, L BENVENISTE, RE TSAI, CC CLARK, EA POLACINO, P WATANABE, R OVERBAUGH, J KATZE, MG MORTON, WR AF KULLER, L BENVENISTE, RE TSAI, CC CLARK, EA POLACINO, P WATANABE, R OVERBAUGH, J KATZE, MG MORTON, WR TI INTRARECTAL INOCULATION OF MACAQUES BY THE SIMIAN IMMUNODEFICIENCY VIRUS, SIVMNE E11S - CD4+ DEPLETION AND AIDS SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article DE HIV-1; IDIOPATHIC CD4+; MUCOSAL INFECTION; T-LYMPHOCYTOPENIA ID UNEXPLAINED OPPORTUNISTIC INFECTIONS; T-LYMPHOCYTOPENIA; HOMOSEXUAL MEN; HIV-INFECTION; GENERALIZED LYMPHADENOPATHY; GENOME ORGANIZATION; SEXUAL PRACTICES; CELL SUBSETS; RISK-FACTORS; HTLV-III AB Macaca nemestrina and Macaca fascicularis were inoculated with various doses of a single-cell clone of SIVmne-infected HuT 78 cells (E11S) by both the intravenous and intrarectal routes. Animals inoculated intravenously at each dose seroconverted and virus was isolated from peripheral blood mononuclear cells, but only the high-dose intrarectally exposed macaques became viremic and seroconverted. However, some seronegative, virus isolation negative intrarectally inoculated macaques showed evidence of infection and disease. C1 UNIV WASHINGTON,DEPT MICROBIOL,SEATTLE,WA 98195. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD. RP KULLER, L (reprint author), UNIV WASHINGTON,REG PRIMATE RES CTR,SJ-50,SEATTLE,WA 98195, USA. FU NCRR NIH HHS [RR00166]; NIAID NIH HHS [U01-AI26503] NR 42 TC 24 Z9 24 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD SEP PY 1994 VL 23 IS 7 BP 397 EP 409 PG 13 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA QE407 UT WOS:A1994QE40700006 PM 7731030 ER PT J AU HSIA, CC DIBISCEGLIE, AM KLEINER, DE FARSHID, M TABOR, E AF HSIA, CC DIBISCEGLIE, AM KLEINER, DE FARSHID, M TABOR, E TI RB TUMOR-SUPPRESSOR GENE-EXPRESSION IN HEPATOCELLULAR CARCINOMAS FROM PATIENTS INFECTED WITH THE HEPATITIS-B VIRUS SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE HEPATITIS B SURFACE ANTIGEN; P53; IMMUNOHISTOCHEMICAL STAINING ID RETINOBLASTOMA GENE; PROTEIN EXPRESSION; ALTERED EXPRESSION; BLADDER-CANCER; P53 GENE; HUMAN SARCOMAS; PRODUCT; PROGRESSION; MUTATIONS AB Hepatitis B virus (HBV) infection is closely associated with the development of hepatocellular carcinoma (HCC), but definite mechanisms by which it could play an etiologic role have not yet been identified. Modifications of the function of the RB tumor suppressor gene, which regulates the cell cycle, could provide such a mechanism. In the present study, the expression of the protein product of RB, pRB, was evaluated by immunohistochemical staining in HCC tissues from 25 patients from China and the United States, adjacent nontumorous liver from 19 of those patients, five human HCC cell lines, three human hepatoblastoma cell lines, and five specimens of normal human liver. Representative samples were also evaluated by western blot. Altered expression of RB was detected in eight HCC tissues (pRB undetectable in five HCCs and detected in <1% of nuclei of HCC cells in three others); all eight had detectable hepatitis B surface or core antigen in the adjacent nontumorous liver, indicating active HBV infection. pRB was detected in 10-95% of nuclei (normal expression) in the remaining 17 HCCs, and in many nuclei in all 19 nontumorous livers, and in the 5 normal livers. No pRB staining was detected in the nuclei of three HCC cell lines, but pRB was detected in >90% of nuclei of the other HCC and hepatoblastoma cell lines. The relationship of pRB expression to mutations of the p53 tumor suppressor gene was also examined. The absence of detectable nuclear pRB by immunohistochemical staining was associated with the presence of presumed mutant p53 detected by immunohistochemical staining in four out of five HCC cases. In addition, all three HCC cell lines lacking detectable pRB also had a p53 mutation or a p53 deletion. HCCs with altered pRB expression included more grade III and IV tumors (8/8, 100%) than did HCCs with normal pRB expression (7/17, 41%) (P < 0.02), suggesting that abnormal pRB expression may be associated with more advanced histologic grades of HCC. These data indicate that interference with the normal function of the tumor suppressor gene RB or its product pRB, often with concomitant p53 mutation, may be one of several mechanisms that contribute to the development or progression of HCC in humans infected with HBV. (C) 1994 Wiley-Liss, Inc. C1 NCI,DIV CANC ETIOL,BIOL CARCINOGENESIS PROGRAM,BETHESDA,MD 20892. NIDDKD,LIVER DIS SECT,BETHESDA,MD 20892. NCI,DIV CANC BIOL & DIAG,PATHOL LAB,BETHESDA,MD 20892. OI Kleiner, David/0000-0003-3442-4453 NR 23 TC 27 Z9 27 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD SEP PY 1994 VL 44 IS 1 BP 67 EP 73 DI 10.1002/jmv.1890440113 PG 7 WC Virology SC Virology GA PE105 UT WOS:A1994PE10500012 PM 7798888 ER PT J AU LOCKWICH, TP KIM, IH AMBUDKAR, IS AF LOCKWICH, TP KIM, IH AMBUDKAR, IS TI TEMPERATURE-DEPENDENT MODIFICATION OF DIVALENT-CATION FLUX IN THE RAT PAROTID-GLAND BASOLATERAL MEMBRANE SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE DIVALENT CATIONS; BASOLATERAL MEMBRANE VESICLES; CA2+ FLUX; MN2+ INFLUX; RAT PAROTID ACINAR CELLS; CARBACHOL ID CAPACITATIVE CALCIUM-ENTRY; INTRACELLULAR CA2+ STORES; ACINAR-CELLS; TYROSINE PHOSPHORYLATION; INOSITOL PHOSPHATES; PLASMA-MEMBRANE; SENSORY NEURONS; CA-2+ RELEASE; MAST-CELLS; INFLUX AB Divalent cation (Mn2+, Ca2+) entry into rat parotid acinar cells is stimulated by the release of Ca2+ from the internal agonist-sensitive Ca2+ pool via a mechanism which is not yet defined. This study examines the effect of temperature on Mn2+ influx into internal Ca2+ pool-depleted acini (depl-acini, as a result of carbachol stimulation of acini in a Ca2+-free medium for 10 min) and passive Ca-45(2+) influx in basolateral membrane vesicles (BLMV). Mn2+ entry into depl-acini was decreased when the incubation temperature was lowered from 37 to 4 degrees C. At 4 degrees C, Mn2+ entry appeared to be inactivated since it was not increased by raising extracellular [Mn2+] from 50 mu M up to 1 mM. The Arrhenius plot of depletion-activated Mn2+ entry between 37 and 8 degrees C was nonlinear, with a change in the slope at about 21 degrees C. The activation energy (E(a)) increased from 10 kcal/mol (Q(10) = 1.7) at 21-37 degrees C to 25 kcal/mol (Q(10) = 3.0> at 21-8 degrees C. Under the same conditions, Mn2+ entry into basal (unstimulated) cells and ionomycin (5 mu M) permeabilized depl-acini exhibit a linear decrease, with E(a) of 7.8 kcal/mol (Q(10) = 1.5> and 6.2 kcal/mol(Q(10) < 1.5),respectively. These data suggest that depletion-activated Mn2+ entry into parotid acini is regulated by a mechanism which is strongly temperature dependent and distinct from Mn2+ entry into unstimulated acini. As in intact acini, Ca2+ influx into BLMV was decreased (by 40%) when the temperature of the reaction medium was lowered from 37 to 4 degrees C. Kinetic analysis of the initial rates of Ca2+ influx in BLMV at 37 degrees C demonstrated the presence of two Ca2+ influx components:a saturable component, with K-Ca = 279 +/- 43 mu M, V-max = 3.38 +/- 0.4 nmol Ca2+/mg protein/min, and an apparently unsaturable component. At 4 degrees C, there was no significant change in the affinity of the saturable component, but V-max decreased by 61% to 1.3 +/- 0.4 nmol Ca2+/mg protein/min. There was no detectable change in the unsaturable component. When BLMV were treated with DCCD (5 mM) or trypsin (1:100, enzyme to membrane) for 30 min at 37 degrees C there was a 40% decrease in Ca2+ influx. When BLMV were treated with DCCD or trypsin at 4 degrees C and subsequently assayed for Ca2+ uptake at 37 degrees C there was no significant loss of Ca2+ influx. These data suggest that the temperature-sensitive high affinity Ca2+ flux component in BLMV is mediated by a protein which undergoes a modification at low temperatures, resulting in decreased Ca2+ transport. C1 NIDR,SECRETORY PHYSIOL SECT,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. NR 33 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD SEP PY 1994 VL 141 IS 3 BP 289 EP 296 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA PG901 UT WOS:A1994PG90100009 PM 7807527 ER PT J AU SLATTERY, JP JOHNSON, WE GOLDMAN, D OBRIEN, SJ AF SLATTERY, JP JOHNSON, WE GOLDMAN, D OBRIEN, SJ TI PHYLOGENETIC RECONSTRUCTION OF SOUTH-AMERICAN FELIDS DEFINED BY PROTEIN ELECTROPHORESIS SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE PHYLOGENY; FELIDAE; PROTEIN ELECTROPHORESIS; MOLECULAR EVOLUTION ID MOLECULAR PHYLOGENY; GENETIC-DISTANCE; TREES; DIVERGENCE; CARNIVORES; PRIMATES; CHEETAH AB Phylogenetic associations among six closely related South American felid species were defined by changes in protein-encoding gene loci. We analyzed proteins isolated from skin fibroblasts using two-dimensional electrophoresis and allozymes extracted from blood cells. Genotypes were determined for multiple individuals of ocelot, margay, tigrina, Geoffroy's cat, kodkod, and pampas cat at 548 loci resolved by two-dimensional electrophoresis and 44 allozyme loci. Phenograms were constructed using the methods of Fitch-Margoliash and neighbor-joining on a matrix of Nei's unbiased genetic distances for all pairs of species. Results of a relative-rate test indicate changes in two-dimensional electrophoresis data are constant among all South American felids with respect to a hyena outgroup. Allelic frequencies were transformed to discrete character states for maximum parsimony analysis. Phylogenetic reconstruction indicates a major split occurred approximately 5-6 million years ago, leading to three groups within the ocelot lineage. The earliest divergence led to Leopardus tigrina, followed by a split between an ancestor of an unresolved trichotomy of three species (Oncifelis guigna, O. geoffroyi, and Lynchailuris colocolo) and a recent common ancestor of Leopardus paradalis and L. wiedii. The results suggest that modern South American felids are monophyletic and evolved rapidly after the formation of the Panama land bridge between North and South America. C1 FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,FREDERICK,MD 21702. NIAAA,CLIN STUDIES LAB,BETHESDA,MD 20892. RI Johnson, Warren/D-4149-2016; Goldman, David/F-9772-2010 OI Johnson, Warren/0000-0002-5954-186X; Goldman, David/0000-0002-1724-5405 NR 53 TC 25 Z9 27 U1 0 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD SEP PY 1994 VL 39 IS 3 BP 296 EP 305 DI 10.1007/BF00160153 PG 10 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA PB539 UT WOS:A1994PB53900007 PM 7932791 ER PT J AU WEIHE, E SCHAFER, MKH ERICKSON, JD EIDEN, LE AF WEIHE, E SCHAFER, MKH ERICKSON, JD EIDEN, LE TI LOCALIZATION OF VESICULAR MONOAMINE TRANSPORTER ISOFORMS (VMAT1 AND VMAT2) TO ENDOCRINE-CELLS AND NEURONS IN RAT SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE VESICULAR MONOAMINE TRANSPORTER ISOFORMS; VMAT1; VMAT2; RAT NEUROENDOCRINE SYSTEM ID MAST-CELLS; CHROMAFFIN; HISTAMINE; CLONING AB Polyclonal antipeptide antibodies have been raised against each of the two isoforms of the rat vesicular monoamine transporter, VMAT1 and VMAT2. Antibody specificity was determined by isoform-specific staining of monkey fibroblasts programmed to express either VMAT1 or VMAT2. The expression of VMAT1 and VMAT2 in the diffuse neuroendocrine system of the rat has been examined using these polyclonal antibodies specific for either VMAT1 or VMAT2. VMAT1 is expressed exclusively in endocrine/paracrine cells associated with the intestine, stomach, and sympathetic nervous system. VMAT2 is expressed in neurons of the sympathetic nervous system, and aminergic neurons in the enteric and central nervous systems. VMAT2 is expressed in at least two endocrine cell populations in addition to its expression in neurons. A subpopulation of chromogranin A (CGA)-expressing chromaffin cells of the adrenal medulla also express VMAT2, and the oxyntic mucosa of the stomach contains a prominent population of CGA- and VMAT2-positive endocrine cells. The expression of VMAT2 in neurons, and the mutually exclusive expression of VMAT1 and VMAT2 in endocrine/paracrine cell populations of stomach, intestine, and sympathetic nervous system may provide a marker for, and insight into, the ontogeny and monoamine-secreting capabilities of multiple neuroendoerine sublineages in the diffuse neuroendocrine system. C1 NIMH,CELL BIOL LAB,MOLEC NEUROSCI SECT,BETHESDA,MD 20892. UNIV MARBURG,DEPT ANAT & CELL BIOL,MARBURG,GERMANY. OI Eiden, Lee/0000-0001-7524-944X NR 17 TC 151 Z9 154 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07012 SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD FAL PY 1994 VL 5 IS 3 BP 149 EP 164 DI 10.1007/BF02736730 PG 16 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA QV568 UT WOS:A1994QV56800003 PM 7654518 ER PT J AU HAYES, WP AF HAYES, WP TI THE TRH NEURONAL PHENOTYPE FORMS EMBRYONIC-CELL CLUSTERS THAT GO ON TO ESTABLISH A REGIONALIZED CELL FATE IN FOREBRAIN SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE DIENCEPHALON; NEUROGENESIS; NEUROPEPTIDES; THYROTROPIN-RELEASING HORMONE (TRH); XENOPUS ID THYROTROPIN-RELEASING-HORMONE; OLFACTORY PLACODE ABLATION; MESSENGER RIBONUCLEIC-ACID; DEVELOPING CEREBRAL-CORTEX; GENE-EXPRESSION; XENOPUS-LAEVIS; RESTRICTED EXPRESSION; INSITU HYBRIDIZATION; TRANSCRIPTION FACTOR; MOUSE CEREBELLUM AB How neurons diversify in developing brain to produce discrete cell fates in their appropriate regions remains a fundamental question. Embryonic Xenopus was previously used to identify juxtaposed embryonic cells that first express proopiomelanocortin mRNA in forebrain and pituitary, supporting the idea that this neuropeptide phenotype is induced locally (Hayes and Loh, 1990, Development 110: 747-757). To begin to examine how a more widespread population of forebrain cells is set up, the present focus is on the thyrotropin-releasing hormone (TRH) phenotype. Serial section in situ hybridization histochemistry produced the unexpected finding that the adult-like TRH system spanning forebrain and comprising over six different telencephalic and diencephalic nuclei, is preceded by an embryonic TRH cell population that is initially localized and then highly regionalized in the area from which the adult pattern develops. Thus, the first TRH cells, detected in vivo after 35 h (stage 29/30), were confined to discrete anterior or posterior bilateral clusters in embryonic forebrain or hindbrain. Thereafter, the TRH cell clusters in diencephalon, but not hindbrain, expanded to form rows, extending anteriorly into telencephalon and bifurcating posteriorly around the infundibulum. By 80 h (stage 42), after extensive brain morphogenesis, these forebrain rows showed regional differences in levels of TRH mRNA corresponding to the specific brain nuclei that have been shown to contain TRH cells in adult. These findings show that subsets of phenotype-specific forebrain cells first form a regionalized neuronal cell fate before distinct brain nuclei form. This in turn points to the testable hypothesis in Xenopus that certain neuronal cell fates in forebrain may be dictated by cell lineage or local induction. (C) 1994 John Wiley and Sons, Inc. C1 NICHHD,CELLULAR NEUROBIOL SECT,DEV NEUROBIOL LAB,BETHESDA,MD 20892. NR 83 TC 3 Z9 3 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD SEP PY 1994 VL 25 IS 9 BP 1095 EP 1112 DI 10.1002/neu.480250906 PG 18 WC Neurosciences SC Neurosciences & Neurology GA PC777 UT WOS:A1994PC77700005 PM 7815066 ER PT J AU KAROUM, F CHRAPUSTA, SJ EGAN, MF AF KAROUM, F CHRAPUSTA, SJ EGAN, MF TI 3-METHOXYTYRAMINE IS THE MAJOR METABOLITE OF RELEASED DOPAMINE IN THE RAT FRONTAL-CORTEX - REASSESSMENT OF THE EFFECTS OF ANTIPSYCHOTICS ON THE DYNAMICS OF DOPAMINE RELEASE AND METABOLISM IN THE FRONTAL-CORTEX, NUCLEUS-ACCUMBENS, AND STRIATUM BY A SIMPLE 2-POOL MODEL SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE DOPAMINE RELEASE; METABOLISM; FRONTAL CORTEX; 3-METHOXYTYRAMINE; 3,4-DIHYDROXYPHENYLACETIC ACID ID CATECHOL-O-METHYLTRANSFERASE; 3,4-DIHYDROXYPHENYLACETIC ACID DOPAC; CENTRALLY ACTING DRUGS; MONOAMINE-OXIDASE; PREFRONTAL CORTEX; SUBSTANTIA NIGRA; EXTRACELLULAR DOPAMINE; ELECTRICAL-STIMULATION; INTRACEREBRAL DIALYSIS; METHYL-TRANSFERASE AB 3-Methoxytyramine (3-MT) and 3,4-dihydroxyphenylacetic acid (DOPAC) rates of formation were used, respectively, to assess the dynamics of dopamine (DA) release and turnover in the rat frontal cortex, nucleus accumbens, and striatum. Assuming total (re)uptake and metabolism of released DA are relatively uniform among the three brain regions, a simplified two pool model was used to assess the metabolic fate of released DA. Under basal conditions, 3-MT formation was found to comprise >60% of total DA turnover (sum of 3-MT plus DOPAC rates of formation) in the frontal cortex, and not more than 15% in the nucleus accumbens and striatum. Haloperidol increased the 3-MT rate of formation to a greater extent in the frontal cortex than in the two other regions. Clozapine increased the 3-MT rate of formation in the frontal cortex and decreased it in the striatum. Both drugs increased DOPAC rate of formation in the frontal cortex and nucleus accumbens. It was elevated by haloperidol but not clozapine in the striatum. It is concluded that (1) O-methylation is a prominent step in the catabolism of DA in the frontal cortex under both physiological conditions and after acute treatment with antipsychotics, (2) 3-MT is the major metabolite of released DA in the frontal cortex and possibly also in the nucleus accumbens and striatum, (3) in contrast to the frontal cortex, most of the DOPAC in the nucleus accumbens and striatum appear to originate from intraneuronal deamination of DA that has not been released, (4) because presynaptic uptake and metabolism of DA give rise to DOPAC, whereas postsynaptic uptake and metabolism produced both DOPAC and 3-MT, the ratio of 3-MT to DOPAC rates of formation can be a useful index of reuptake inhibition. RP KAROUM, F (reprint author), NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,INTRAMURAL RES PROGRAM,WASHINGTON,DC 20032, USA. NR 65 TC 237 Z9 239 U1 0 U2 5 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 1994 VL 63 IS 3 BP 972 EP 979 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA PC937 UT WOS:A1994PC93700020 PM 7914228 ER PT J AU MILSTIEN, S SAKAI, N BREW, BJ KRIEGER, C VICKERS, JH SAITO, K HEYES, MP AF MILSTIEN, S SAKAI, N BREW, BJ KRIEGER, C VICKERS, JH SAITO, K HEYES, MP TI CEREBROSPINAL-FLUID NITRITE/NITRATE LEVELS IN NEUROLOGIC DISEASES SO JOURNAL OF NEUROCHEMISTRY LA English DT Note DE NITRIC OXIDE; QUINOLINIC ACID; NEOPTERIN; INFLAMMATORY NEUROLOGIC DISEASE; NITRITE/NITRATE ID NITRIC-OXIDE PRODUCTION; NITROGEN-OXIDES; QUINOLINIC ACID; INTERFERON-GAMMA; L-ARGININE; TETRAHYDROBIOPTERIN; METABOLISM; INDUCTION; SYNTHASE; BRAIN AB Nitric oxide has been proposed to mediate cytotoxic effects in inflammatory diseases. To investigate the possibility that overproduction of nitric oxide might play a role in the neuropathology of inflammatory and noninflammatory neurological diseases, we compared levels of the markers of nitric oxide, nitrite plus nitrate, in the CSF of controls with those in patients with various neurologic diseases, including Huntington's and Alzheimer's disease, amyotrophic lateral sclerosis, and HIV infection. We found that there were no significant increases in the CSF levels of these nitric oxide metabolites, even in patients infected with HIV or in monkeys infected with poliovirus, both of which have significantly elevated levels of the neurotoxin quinolinic acid and the marker of macrophage activation, neopterin. However, CSF quinolinic acid, neopterin, and nitrite/nitrate levels were significantly increased in a small group of patients with bacterial and viral meningitis. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. US FDA,DIV SAFETY,BETHESDA,MD. ST VINCENTS MED CTR,DEPT NEUROL,SYDNEY,NSW,AUSTRALIA. UNIV BRITISH COLUMBIA,DEPT NEUROL,VANCOUVER,BC,CANADA. RP MILSTIEN, S (reprint author), NIMH,NEUROCHEM LAB,BLDG 36,ROOM 3D-30,BETHESDA,MD 20892, USA. RI Brew, Bruce/J-6513-2012 NR 19 TC 100 Z9 101 U1 1 U2 6 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 1994 VL 63 IS 3 BP 1178 EP 1180 PG 3 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA PC937 UT WOS:A1994PC93700047 PM 8051562 ER PT J AU HITRI, A WYATT, RJ AF HITRI, A WYATT, RJ TI QUESTIONS ABOUT THE DOPAMINERGIC NATURE OF [H-3] GBR-12935 BINDING IN THE HUMAN FRONTAL-CORTEX SO JOURNAL OF NEUROCHEMISTRY LA English DT Letter ID H-3 C1 GEORGETOWN UNIV,SCH MED,WASHINGTON,DC. NIMH,NEUROPSYCHIAT BRANCH,WASHINGTON,DC. RP HITRI, A (reprint author), DEPT VET AFFAIRS MED CTR,WASHINGTON,DC 20422, USA. NR 8 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 1994 VL 63 IS 3 BP 1181 EP 1182 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA PC937 UT WOS:A1994PC93700048 PM 8051563 ER PT J AU GOLOMB, D WANG, XJ RINZEL, J AF GOLOMB, D WANG, XJ RINZEL, J TI SYNCHRONIZATION PROPERTIES OF SPINDLE OSCILLATIONS IN A THALAMIC RETICULAR NUCLEUS MODEL SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID INHIBITORY POSTSYNAPTIC CURRENTS; THALAMOCORTICAL RELAY NEURONS; COUPLED PHASE OSCILLATORS; ELECTROPHYSIOLOGICAL PROPERTIES; GABAERGIC NEURONS; PYRAMIDAL NEURONS; ABSENCE SEIZURES; CALCIUM CURRENT; RAT; CAT AB 1. We address the hypothesis of Steriade and colleagues that the thalamic reticular nucleus (RE) is a pacemaker for thalamocortical spindle oscillations by developing and analyzing a model of a large population of all-to-all coupled inhibitory RE neurons. 2. Each RE neuron has three ionic currents: a low-threshold T-type Ca2+ current (I-Ca-T), a calcium-activated potassium current (I-AHP) and a leakage current (I-L). I-Ca-T underlies a cell's postinhibitory rebound properties, whereas I-AHP hyperpolarizes the neuron after a burst. Each neuron, which is a conditional oscillator, is coupled to all other RE neurons via fast gamma-aminobutyric acid-A (GABA(A)) and slow GABA(B) synapses. 3. For generating network oscillations I-AHP may not be necessary. Synaptic inhibition can provide the hyperpolarization for deinactivating I-Ca-T that causes bursting if the reversal potentials for GABA(A) and GABA(B) synapses are sufficiently negative. 4. If model neurons display sufficiently powerful rebound excitability, an isolated RE network of such neurons oscillates with partial but typically not full synchrony. The neurons spontaneously segregate themselves into several macroscopic clusters. The neurons within a cluster follow the same time course, but the clusters oscillate differently from one another. In addition to activity patterns in which clusters burst sequentially (e.g., 2 or 3 clusters bursting alternately), a two-cluster state may occur with one cluster active and one quiescent. Because the neurons are all-to-all coupled, the cluster states do not have any spatial structure. 5. We have explored the sensitivity of such partially synchronized patterns to heterogeneity in cells' intrinsic properties and to simulated neuroelectric noise. Although either precludes precise clustering, modest levels of heterogeneity or noise lead to approximate clustering of active cells. The population-averaged voltage may oscillate almost regularly but individual cells burst at nearly every second cycle or less frequently. The active-quiescent state is not robust at all to heterogeneity or noise. Total asynchrony is observed when heterogeneity or noise is too large, e.g., even at 25% heterogeneity for our reference set of parameter values. 6. The fast GABA(A) inhibition (with a reversal potential more negative than, say, -65 mV) favors the cluster states and prevents full synchrony. Our simulation results suggest two mechanisms that can fully synchronize the isolated RE network model. With GABA(A) removed or almost totally blocked, GABA(B) inhibition (because it is slow) can lead to full synchrony, which is partially robust to heterogeneity and noise. A second possibility, also robust to heterogeneity and noise, is realized if the GABA(A) synapses have a less negative reversal potential and provide shunting rather than hyperpolarizing inhibition. 7. We examined the effects of fast excitation from thalamocortical(TC) cells. The TC output is generated by a synchronous TC pool that receives GABA(A) and GABA(B) inhibition from the RE network and sends back amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-mediated excitation. The TC pool has three ionic currents: I-Ca-T, I-L, and a hyperpolarization-activated cation (''sag'') current, I-sag. 8. Modest excitation from the TC pool can eliminate cluster oscillations and synchronize fully the RE network, with robustness to heterogeneity and noise. Furthermore, strong AMPA excitation can create synchronized oscillations in cases where without it the RE system is at rest. 9. The oscillation frequency of the RE-TC network depends mainly on the GABA inhibition from the RE cells to the TC pool. Blocking GABA(A) decreases the frequency because of an indirect enhancement of the sag current in the TC pool, whereas blocking GABA(B) increases it. C1 UNIV PITTSBURGH,DEPT MATH,PITTSBURGH,PA 15260. RP GOLOMB, D (reprint author), NIDDKD,MATH RES BRANCH,BETHESDA,MD 20814, USA. RI Wang, Xiao-Jing/D-2722-2009 NR 76 TC 131 Z9 132 U1 1 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 1994 VL 72 IS 3 BP 1109 EP 1126 PG 18 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA PH091 UT WOS:A1994PH09100005 PM 7807198 ER PT J AU GOSSARD, JP FLOETER, MK KAWAI, Y BURKE, RE CHANG, T SCHIFF, SJ AF GOSSARD, JP FLOETER, MK KAWAI, Y BURKE, RE CHANG, T SCHIFF, SJ TI FLUCTUATIONS OF EXCITABILITY IN THE MONOSYNAPTIC REFLEX PATHWAY TO LUMBAR MOTONEURONS IN THE CAT SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID MEDIAL GASTROCNEMIUS MOTONEURONS; POST-TETANIC POTENTIATION; TWITCH MOTOR UNITS; IA AFFERENT-FIBERS; PRESYNAPTIC INHIBITION; DECEREBRATE CAT; SYNAPTIC INPUT; EPSPS; TRANSMISSION; STIMULATION AB 1. It is well known that the amplitude of successive monosynaptic reflexes (MSR), elicited by afferent stimuli of constant strength, fluctuate from trial to trial. Previous evidence suggests that such excitability fluctuations within the motor pool can be introduced either pre- and/or postsynaptically. Using unanesthetized decerebrate or decerebrate/spinal cats, we attempted to evaluate the relative importance of pre- and postsynaptic mechanisms to MSR variability and the potential contribution of changes in the identities of responding motoneurons to such variability. 2. Comparisons between the MSR amplitude, measured in a severed ventral root, and the probability of firing of up to three individual motoneurons in fine filaments teased from the same root, confirmed that both correlated and uncorrelated fluctuations of motoneuron excitability are involved in MSR variability. Linear regression analysis from concurrent intracellular recordings from homonymous motoneurons showed that the MSR fluctuations were correlated with the variations in membrane potential baseline, as well as with the fluctuations in the monosynaptic excitatory postsynaptic potential peak amplitude. In all 11 cases tested, the former correlation was stronger than the latter. 3. Stimulation of the caudal cutaneous sural nerve (CCS) was used to alter the postsynaptic potential background on which triceps surae (GS) MSRs were generated. The interval chosen between CCS conditioning and the GS stimulation excluded the involvement of presynaptic inhibition. When conditioned by preceding CCS stimulation, GS population MSRs generally (8/9 cases tested) increased in amplitude without much change in their overall variance. However, the individual motoneurons that contributed to the population responses did show changes in both relative excitability and in the uncorrelated component of their response variance. About half of the concurrently recorded motoneurons (6/13) showed a decrease in relative excitability after CCS conditioning, 5/13 showed an increase, and 2/13 were unchanged. Comparison of unit and population responses indicated that the identities of the motoneurons that responded at any given level of population response were quite different with and without CCS conditioning. 4. High-frequency stimulation of Ia fibers was used to alter the state of presynaptic Group Ia-afferents that produced population MSRs. Post tetanic potentiation following high-frequency stimulation did not greatly alter the variance of population MSRs or ratio of correlated and uncorrelated fluctuations in MSR responses among individual motoneurons within the responding population. However, intratetanic depression acid posttetanic potentiation of population MSRs were accompanied by marked shifts in individual motoneuron excitability relative to the population response, again indicated that changes in the identities of responding motoneurons contributes to population response fluctuations. 5. These results, which were similar in decerebrate and spinal preparations, indicate that both pre- and postsynaptic mechanisms produce the fluctuations of excitability in motoneurons during the MSR, with predominance of the latter. Correlated postsynaptic input to motoneurons from common sources appears to explain a large fraction of the variability of MSRs under the conditions studied. Our observations also strongly suggest that the identity of the motoneurons that participate in population MSRs can change under different conditions, presumably because of differences in the organization of synaptic input to different species of motoneurons. C1 NIH, NEURAL CONTROL LAB, BETHESDA, MD 20892 USA. CHILDRENS NATL MED CTR, DEPT NEUROSURG, WASHINGTON, DC USA. FU NIMH NIH HHS [1 R29 MH-50006] NR 38 TC 30 Z9 30 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 1994 VL 72 IS 3 BP 1227 EP 1239 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA PH091 UT WOS:A1994PH09100016 PM 7807207 ER PT J AU WEINBERGER, DR ALOIA, MS GOLDBERG, TE BERMAN, KF AF WEINBERGER, DR ALOIA, MS GOLDBERG, TE BERMAN, KF TI THE FRONTAL LOBES AND SCHIZOPHRENIA SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID CEREBRAL BLOOD-FLOW; DORSOLATERAL PREFRONTAL CORTEX; CARD SORTING TEST; PHYSIOLOGICAL DYSFUNCTION; STRUCTURAL ABNORMALITIES; HUNTINGTONS-DISEASE; COGNITIVE FUNCTION; MONOZYGOTIC TWINS; HOMOVANILLIC-ACID; BRAIN PATHOLOGY AB Many patients with schizophrenia show clinical signs of frontal lobe dysfunction, including blunted affect, difficulty with problem solving, and impoverished thinking. The authors present cytoarchitectural, neuropsychological, and functional neuroanatomical evidence of frontal abnormalities from recent studies of frontal dysfunction in schizophrenia. It is suggested that the failure of intracortical connectivity of the prefrontal cortex accounts for both cognitive and psychotic manifestations of this illness. RP WEINBERGER, DR (reprint author), NIMH, NEUROSCI CTR ST ELIZABETHS, INTRAMURAL RES PROGRAM, WASHINGTON, DC 20032 USA. NR 54 TC 150 Z9 154 U1 3 U2 7 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 1994 VL 6 IS 4 BP 419 EP 427 PG 9 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA PN731 UT WOS:A1994PN73100010 PM 7841813 ER PT J AU INSEL, TR WANG, ZX FERRIS, CF AF INSEL, TR WANG, ZX FERRIS, CF TI PATTERNS OF BRAIN VASOPRESSIN RECEPTOR DISTRIBUTION ASSOCIATED WITH SOCIAL-ORGANIZATION IN MICROTINE RODENTS SO JOURNAL OF NEUROSCIENCE LA English DT Article DE VASOPRESSIN; AVP; VOLE; SEPTUM; THALAMUS; PHOSPHOINOSITOL; MONOGAMY ID BINDING-SITES; ARGININE-VASOPRESSIN; PRAIRIE VOLES; RAT-BRAIN; AFFILIATIVE BEHAVIOR; GOLDEN-HAMSTER; MEADOW VOLES; OXYTOCIN; OCHROGASTER; SEPTUM AB Central vasopressin pathways have been implicated in the mediation of paternal behavior, selective aggression, and affiliation in monogamous prairie voles. Here we demonstrate markedly different patterns of brain vasopressin receptor binding in the monogamous prairie vote and the congeneric nonmonogamous (promiscuous) montane vole. Vasopressin binding was assessed with both H-3-vasopressin and I-125-sarc-AVP using receptor autoradiography. The specificity of binding was consistent with a V-1a receptor, the saturation kinetics were similar in the two species, and neither species showed evidence of sexual dimorphisms. In the prairie vole, highest specific binding was observed in the accessory olfactory bulb, diagonal band, laterodorsal thalamus, and superior colliculus. In the montane vole, specific binding was observed in the accessory olfactory bulb and superior colliculus as well, but in several other regions with high levels of binding in the prairie vole, binding was low or undetectable in the montane vole. In this nonmonogamous species, specific binding was high in lateral septum. Functional studies demonstrated the induction of phosphoinositol by AVP in the septum of the montane vole but not in the prairie vole. The pattern of I-125-sarc-AVP binding to lateral septum may reflect the social organization of these two species, as similar differences in AVP receptor distribution in the lateral septum were also observed in two related species, pine voles and meadow voles, which are monogamous and nonmonogamous, respectively. These results, along with earlier studies of AVP's effects on pair bonding, suggest the importance of this neuropeptide for the mediation of behaviors related to social organization. C1 UNIV MASSACHUSETTS, DEPT PSYCHOL, AMHERST, MA 01003 USA. UNIV MASSACHUSETTS, MED CTR, DEPT PSYCHIAT, WORCESTER, MA 01655 USA. RP INSEL, TR (reprint author), NIMH, NEUROPHYSIOL LAB, POB 608, POOLESVILLE, MD 20837 USA. NR 45 TC 265 Z9 272 U1 4 U2 34 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP PY 1994 VL 14 IS 9 BP 5381 EP 5392 PG 12 WC Neurosciences SC Neurosciences & Neurology GA PJ126 UT WOS:A1994PJ12600019 PM 8083743 ER PT J AU CAUDLE, RM CHAVKIN, C DUBNER, R AF CAUDLE, RM CHAVKIN, C DUBNER, R TI KAPPA(2) OPIOID RECEPTORS INHIBIT NMDA RECEPTOR-MEDIATED SYNAPTIC CURRENTS IN GUINEA-PIG CA3 PYRAMIDAL CELLS SO JOURNAL OF NEUROSCIENCE LA English DT Article DE OPIOIDS; DYNORPHIN; KAPPA RECEPTORS; N-METHYL-D-ASPARTATE RECEPTORS (NMDA); WHOLE CELL PATCH CLAMP; HIPPOCAMPUS; GUINEA PIG; CA3 ID ENKEPHALIN-LIKE IMMUNOREACTIVITY; ROOT GANGLION NEURONS; DORSAL HORN NEURONS; TAIL-FLICK REFLEX; RAT SPINAL-CORD; DYNORPHIN IMMUNOREACTIVITY; ENDOGENOUS DYNORPHINS; BINDING-SITES; MOSSY FIBERS; HIPPOCAMPUS AB The role of the endogenous opioid peptide dynorphin (1-17) in regulating NMDA receptor-mediated synaptic currents was examined in guinea pig hippocampus. Schaffer collateral/commissural fiber-evoked NMDA synaptic currents were recorded using whole-cell patch-clamp techniques in CA3 pyramidal cells. Dynorphin was found to have dual effects on NMDA synaptic currents, increasing currents at low concentrations and decreasing currents at high concentrations. Only the inhibitory action of dynorphin was sensitive to naloxone, indicating that this effect was mediated by an opioid receptor. The inhibitory effect was mimicked by bremazocine, but not by U69,593, U50,488, [D-Ala(2), N-Me-Phe(4), Gly-ol]-enkephalin, or [D-Pen(2,5)]-enkephalin. Bremazocine's effect was blocked by naloxone, but not by nor-binaltorphimine, cyprodime, or naltrindole. These findings suggest that bremazocine's effect was mediated by the kappa(2) subtype of opioid receptor. In addition, 1 mu M naloxone and antisera to dynorphin (1-17) were found to increase NMDA-mediated synaptic currents. Nor-binaltorphimine, cyprodime, naltrindole, and antisera to met-enkephalin did not increase the NMDA synaptic current. These findings suggest that endogenous dynorphin was acting at kappa(2) receptors to inhibit NMDA receptor-mediated synaptic currents. Overall, these findings indicate that dynorphin is an endogenous agonist for kappa(2) receptors in the CA3 region of the guinea pig hippocampus and that these receptors regulate NMDA receptor function. C1 UNIV WASHINGTON,DEPT PHARMACOL,SEATTLE,WA 98195. RP CAUDLE, RM (reprint author), NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BLDG 49,ROOM 1A-11,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Chavkin, Charles/G-2797-2010 FU NIDA NIH HHS [DA04123] NR 49 TC 78 Z9 79 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP PY 1994 VL 14 IS 9 BP 5580 EP 5589 PG 10 WC Neurosciences SC Neurosciences & Neurology GA PJ126 UT WOS:A1994PJ12600035 PM 7916046 ER PT J AU KIRBY, BA MERRIL, CR GHANBARI, H WALLACE, WC AF KIRBY, BA MERRIL, CR GHANBARI, H WALLACE, WC TI HEAT-SHOCK PROTEINS PROTECT AGAINST STRESS-RELATED PHOSPHORYLATION OF TAU IN NEURONAL PC12 CELLS THAT HAVE ACQUIRED THERMOTOLERANCE SO JOURNAL OF NEUROSCIENCE LA English DT Article DE A68-LIKE TAU; HEAT SHOCK PROTEINS; ACQUIRED THERMOTOLERANCE; PC12 CELLS; PHOSPHORYLATION; NEURITES ID PAIRED HELICAL FILAMENTS; ALZHEIMERS-DISEASE; MICROTUBULE-BINDING; EXPRESSION; PATHOLOGY; EPITOPES; ANTIBODY; ANTIGEN; ALZ-50; A68 AB A68, or PHF-tau, is an abnormally phosphorylated form of the microtubule-associated protein tau, which is a primary protein constituent of paired helical filaments (PHFs) and, ultimately, of Alzheimer's disease-associated neurofibrillary tangles (NFTs). Previously, we have shown that in heat-shocked neuronal PC12 cells, tau is hyperphosphorylated and transformed to an A68-like state as determined by immunologic and biochemical criteria. In the present study, we investigated the role of heat shock protein of 72 kDa (hsp72) in the protection of tau against hyperphosphorylation during heat shock. Neuronal PC12 cells were exposed either directly to a heat shock (45 degrees C for 30 min) or to a conditioning heat stress (43 degrees C for 90 min followed by a 4 hr recovery at 37 degrees C) followed by the heat shock. Hsp72 was maximally induced immediately after heat shock in conditioned (acquired thermotolerant, ATT) cells, while unconditioned (nonacquired thermotolerant, non-ATT) cells required 9 hr of recovery to exhibit maximal hsp72 induction. The differential time course of hsp72 induction during recovery of ATT and non-ATT cells correlated with the presence of normal tau. Immediately after the heat shock, when hsps were maximally induced, ATT cells exhibited the normal form of tau. With longer recovery times, the levels of hsp72 were reduced and tau was hyperphosphorylated. A similar correlation was observed in non-ATT cells. In the presence of L-azetidyl 2-carboxylic acid, ATT cells synthesized nonfunctional hsp72, as exhibited by the inability of the cells to recover from the effects of heat shock. Under these conditions, tau was hyperphosphorylated despite the presence of elevated levels of hsp72. These results implicate functional hsp72 in the protection of tau from hyperphosphorylation and transformation to an A68-like state. C1 NIMH,ST ELIZABETHS HOSP,BIOCHEM GENET LAB,WASHINGTON,DC 20032. MOLEC GERIAT CORP,LAKE BLUFF,IL 60044. NR 26 TC 27 Z9 30 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP PY 1994 VL 14 IS 9 BP 5687 EP 5693 PG 7 WC Neurosciences SC Neurosciences & Neurology GA PJ126 UT WOS:A1994PJ12600045 PM 8083763 ER PT J AU ABBOTT, LC CONFORTI, ML ISAACS, KR CRAWLEY, JN STERCHI, D AF ABBOTT, LC CONFORTI, ML ISAACS, KR CRAWLEY, JN STERCHI, D TI A SIMPLIFIED TECHNIQUE FOR HISTOLOGIC ANALYSIS OF CENTRAL-NERVOUS-SYSTEM TISSUES USING GLYCOL-METHACRYLATE PLASTIC COUPLED WITH PREEMBEDDING IMMUNOCYTOCHEMISTRY SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE TYROSINE HYDROXYLASE; CATECHOLAMINE NEURON; PEROXIDASE-ANTIPEROXIDASE; METHACRYLATE; GLYCOL METHACRYLATE; BRAIN; CEREBELLUM ID TYROSINE-HYDROXYLASE; LOCALIZATION; SECTIONS; RAT; IMMUNOHISTOCHEMISTRY; EXPRESSION; CELLS AB Paraffin and some plastic embedding techniques will destroy many antigens routinely detected by immunocytochemistry performed on frozen tissue sections. However, morphologic quality is compromised to varying extents in frozen tissue, even with the use of cryoprotection. We report a simple glycol-methacrylate (GMA) embedding technique using vibratome-sectioned mouse brain reacted for tyrosine hydroxylase (TH) immunoreactivity before plastic embedding. In this study we used a short (4 h) simple, GMA embedding procedure which subsequently provided 1.5-5.0 mu m sections yielding morphologic details superior to frozen or paraffin sections. Prior to embedding we used a peroxidase-antiperoxidase (PAP) reaction with the 3,3'diaminobenzidine tetrahydrochloride (DAB) chromogen visualizing TH. Several different counterstains were used, demonstrating the versatility of this embedding procedure. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NIMH,CLIN NEUROSCI BRANCH,BEHAV NEUROPHARMACOL UNIT,BETHESDA,MD 20892. RP ABBOTT, LC (reprint author), UNIV ILLINOIS,COLL VET MED,DEPT VET BIOSCI,2001 S LINCOLN AVE,URBANA,IL 61801, USA. NR 25 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD SEP PY 1994 VL 54 IS 1 BP 23 EP 29 DI 10.1016/0165-0270(94)90156-2 PG 7 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA PH096 UT WOS:A1994PH09600003 PM 7529349 ER PT J AU CHEN, CC ANDRICH, MP MICAN, JAM METCALFE, DD AF CHEN, CC ANDRICH, MP MICAN, JAM METCALFE, DD TI A RETROSPECTIVE ANALYSIS OF BONE-SCAN ABNORMALITIES IN MASTOCYTOSIS - CORRELATION WITH DISEASE CATEGORY AND PROGNOSIS SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE MASTOCYTOSIS; BONE SCAN; BONE MARROW ID MAST-CELL DISEASE; SYSTEMIC MASTOCYTOSIS; MARROW; OSTEOPOROSIS; FEATURES AB To investigate the usefulness of bone scintigraphy in systemic mastocytosis (SM), the scans of 73 patients were retrospectively reviewed and correlated with disease category. Methods: A modification of a previously described method for bone scan classification in this disease was used. In addition to the group as a whole, two subsets of patients with multiple bone scans were identified for closer analysis: those with (n = 13) and without (n = 12) scintigraphic evidence of progression of disease. Results: Overall, patients with more aggressive SM tended to have increasingly abnormal initial bone scans (p2 = 0.0003), although there was a considerable degree of overlap. Of patients undergoing serial studies, those with scintigraphic progression also tended to have more aggressive disease (p2 = 0.006) and a poorer prognosis than those with stable bone scans. Conclusions: Both the degree of abnormality on initial bone scan and progression of scintigraphic abnormalities with serial scanning appear to correlate with the presence of more aggressive systemic mastocytosis. Based on the patterns seen, in many cases this may be a reflection of bone marrow expansion, which in turn probably reflects increased marrow disease. RP CHEN, CC (reprint author), NIAID,DEPT NUCL MED,WARREN G MAGNUSON CLIN CTR,CLIN INVEST LAB,ALLERG DIS SECT,BETHESDA,MD 20892, USA. NR 17 TC 20 Z9 20 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD SEP PY 1994 VL 35 IS 9 BP 1471 EP 1475 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PE096 UT WOS:A1994PE09600014 PM 8071694 ER PT J AU GREEN, MV SEIDEL, J STEIN, SD TEDDER, TE KEMPNER, KM KERTZMAN, C ZEFFIRO, TA AF GREEN, MV SEIDEL, J STEIN, SD TEDDER, TE KEMPNER, KM KERTZMAN, C ZEFFIRO, TA TI HEAD MOVEMENT IN NORMAL SUBJECTS DURING SIMULATED PET BRAIN IMAGING WITH AND WITHOUT HEAD RESTRAINT SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE PET; BRAIN IMAGING; HEAD MOVEMENT ID POSITRON EMISSION TOMOGRAPHY; ALIGNMENT; IMAGES AB Head movement during brain imaging is recognized as a source of image degradation in PET and most other forms of medical brain imaging. However, little quantitative information is available on the kind and amount of head movement that actually occurs during these studies. We sought to obtain this information by measuring head movement in normal volunteers. Methods: Head position data were acquired for 40 min in each of 13 supine subjects with and without head restraint. These data were then used to drive a mathematically simulated head through exactly the same set of movements. The positions of point sources embedded in this head were computed at each location and these data summarized as movement at FWHM in each of the three coordinate directions. Results: Head movement increased with the length of the sampling interval for studies of either type (with or without head restraint), but the amount and rate of increase with restraint was much smaller. In contrast, head movement during consecutive, short sampling intervals was small and did not increase with time. Spatial gradients in head movement were detected within each study type, and significant spatial differences in head movement were found between study types. Conclusions: Head movements in normal, supine subjects, though small, can cause the effective resolution of a brain imaging study to appear to vary in space and time. These effects can be reduced significantly with head restraint and may also be reduced by dividing the acquisition of a single image into a sequence of short images (instead of a single long image), aligning these images spatially and summing the result. RP GREEN, MV (reprint author), NINCDS,MED NEUROL BRANCH,DIV COMP RES & TECHNOL,COMP SCI LAB,NATL CTR RES RESOURCES,BIOMED ENGN,BETHESDA,MD 20892, USA. NR 8 TC 65 Z9 65 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD SEP PY 1994 VL 35 IS 9 BP 1538 EP 1546 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PE096 UT WOS:A1994PE09600025 PM 8071706 ER PT J AU CLIFFORD, C KHOO, CS ERNST, N SCARBROUGH, FE BEECHER, C DWYER, J FURR, H MATTHEWS, R CONWAY, J SCHNEEMAN, B COMBS, G OLSON, J ROSENBERG, I AF CLIFFORD, C KHOO, CS ERNST, N SCARBROUGH, FE BEECHER, C DWYER, J FURR, H MATTHEWS, R CONWAY, J SCHNEEMAN, B COMBS, G OLSON, J ROSENBERG, I TI A PANEL DISCUSSION - WHERE SHOULD WE FOCUS OUR ATTENTION SO JOURNAL OF NUTRITION LA English DT Discussion C1 CAMPBELL SOUP CO,RES & DEV,CAMDEN,NJ. NHLBI,BETHESDA,MD. TUFTS UNIV,NEW ENGLAND MED CTR,FRANCES STERN NUTR CTR,BOSTON,MA. UNIV CONNECTICUT,STORRS,CT 06269. BELTSVILLE HUMAN NUTR CTR,BELTSVILLE,MD. UNIV CALIF DAVIS,DEPT NUTR,DAVIS,CA. UNIV SO MISSISSIPPI,COLL HLTH & HUMAN SCI,HATTIESBURG,MS. IOWA STATE UNIV SCI & TECHNOL,DEPT BIOCHEM & BIOPHYS,AMES,IA. RP CLIFFORD, C (reprint author), NCI,DIV CANC PREVENT & CONTROL,DIET & CANC BRANCH,BETHESDA,MD, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD SEP PY 1994 VL 124 IS 9 SU S BP S1793 EP S1798 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA PH406 UT WOS:A1994PH40600017 ER PT J AU DIONNE, RA SNYDER, J HARGREAVES, KM AF DIONNE, RA SNYDER, J HARGREAVES, KM TI ANALGESIC EFFICACY OF FLURBIPROFEN IN COMPARISON WITH ACETAMINOPHEN, ACETAMINOPHEN PLUS CODEINE, AND PLACEBO AFTER IMPACTED 3RD MOLAR REMOVAL SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID DENTAL PAIN; RHEUMATOID-ARTHRITIS; POSTOPERATIVE PAIN; ASPIRIN; IBUPROFEN; AMITRIPTYLINE; SUPPRESSION; DIFLUNISAL; SURGERY; RELIEF C1 UNIV MINNESOTA,SCH DENT,DIV ENDODONT,MINNEAPOLIS,MN 55455. RP DIONNE, RA (reprint author), NIDR,CLIN PHARMACOL UNIT,BLDG 10,ROOM 1N-103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Hargreaves, Kenneth/F-5308-2010 NR 28 TC 23 Z9 23 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD SEP PY 1994 VL 52 IS 9 BP 919 EP 924 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA PE357 UT WOS:A1994PE35700006 PM 8064454 ER PT J AU STRATAKIS, CA MASTORAKOS, G CHROUSOS, GP AF STRATAKIS, CA MASTORAKOS, G CHROUSOS, GP TI INTERLEUKIN-6 ELEVATION IN CRITICALLY ILL INFANTS WITH SEPSIS AND NECROTIZING ENTEROCOLITIS SO JOURNAL OF PEDIATRICS LA English DT Letter RP STRATAKIS, CA (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD SEP PY 1994 VL 125 IS 3 BP 504 EP 504 DI 10.1016/S0022-3476(05)83310-4 PG 1 WC Pediatrics SC Pediatrics GA PF353 UT WOS:A1994PF35300037 PM 8071769 ER PT J AU IMREY, PB CHILTON, NW PIHLSTROM, BL PROSKIN, HM KINGMAN, A LISTGARTEN, MA ZIMMERMAN, SO CIANCIO, SG COHEN, ME DAGOSTINO, RB FINE, D FISCHMAN, SL FLEISS, JL GUNSOLLEY, JC KENT, RL KILLOY, WJ LASTER, LL MARKS, RG VARMA, AO AF IMREY, PB CHILTON, NW PIHLSTROM, BL PROSKIN, HM KINGMAN, A LISTGARTEN, MA ZIMMERMAN, SO CIANCIO, SG COHEN, ME DAGOSTINO, RB FINE, D FISCHMAN, SL FLEISS, JL GUNSOLLEY, JC KENT, RL KILLOY, WJ LASTER, LL MARKS, RG VARMA, AO TI PROPOSED GUIDELINES FOR AMERICAN-DENTAL-ASSOCIATION ACCEPTANCE OF PRODUCTS FOR PROFESSIONAL, NONSURGICAL TREATMENT OF ADULT PERIODONTITIS SO JOURNAL OF PERIODONTAL RESEARCH LA English DT Article DE ADULT PERIODONTITIS; AMERICAN DENTAL ASSOCIATION; EFFICACY; CLINICAL TRIALS ID CLINICAL-TRIALS; DESIGN; ISSUES AB Guidelines are suggested for determining efficacy of products to supplement scaling and root planing in professional, non-surgical treatment of adult periodontitis. They result from an extended process including a conference on clinical trials in gingivitis and periodontitis, a subsequent workshop, and commentary from industrial, academic, professional and governmental members of the periodontal research community on two drafts. Recommendations are made in the broad areas of basic study design, subject and periodontal site selection, clinical management, choice of outcome variables, statistical summarization and analysis, and criteria for acceptance. Prominent dissenting views, with justifications for positions taken here, are also provided. Groundwork is laid for possible future guidelines addressing products for primary prevention or over-the-counter uses, or for determining superiority or equivalence of competing products. However, issues are identified which require further exploration before responsible and widely acceptable recommendations can be made in these areas. The guidelines suggested here are meant to form the basis of an evolving document rather than a static standard. It is suggested that they be reviewed frequently in the light of improvement in the technology available for periodontal research, and the emergence of products representing new approaches to periodontal therapy. C1 UNIV ILLINOIS,DEPT COMMUNITY HLTH,URBANA,IL 61801. UNIV ILLINOIS,DEPT STAT,URBANA,IL 61801. UNIV ILLINOIS,CTR RES ORAL MOLEC BIOL,URBANA,IL 61801. COLUMBIA UNIV,SCH DENT & ORAL SURG,NEW YORK,NY. COLUMBIA UNIV,DIV BIOSTAT,NEW YORK,NY. UNIV MINNESOTA,MINNESOTA CLIN DENT RES CTR,MINNEAPOLIS,MN 55455. EASTMAN DENT CTR,DIV BIOSTAT,ROCHESTER,NY. NIDR,EPIDEMIOL & ORAL DIS PREVENT PROGRAM,BETHESDA,MD 20892. UNIV PENN,DEPT PERIODONT,PHILADELPHIA,PA 19104. UNIV PENN,EPIDEMIOL SECT,PHILADELPHIA,PA 19104. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT BIOMATH,HOUSTON,TX 77030. SUNY BUFFALO,DEPT PERIODONTOL,BUFFALO,NY. SUNY BUFFALO,DEPT ORAL MED,BUFFALO,NY. USN,DENT RES INST,GREAT LAKES,IL. BOSTON UNIV,DEPT MATH,BOSTON,MA 02215. VIRGINIA COMMONWEALTH UNIV,DEPT PERIODONT,RICHMOND,VA. FORSYTH DENT CTR,BOSTON,MA 02115. UNIV MISSOURI,DEPT PERIODONT,KANSAS CITY,MO 64110. UNIV FLORIDA,DEPT STAT,DIV BIOSTAT,GAINESVILLE,FL 32611. SUNY STONY BROOK,DEPT PREVENT MED,STONY BROOK,NY 11794. RP IMREY, PB (reprint author), UNIV ILLINOIS,DEPT MED INFORMAT SCI,URBANA,IL 61801, USA. OI Imrey, Peter/0000-0002-0533-4603 NR 18 TC 19 Z9 19 U1 0 U2 5 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0022-3484 J9 J PERIODONTAL RES JI J. Periodont. Res. PD SEP PY 1994 VL 29 IS 5 BP 348 EP 360 PG 13 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA PM489 UT WOS:A1994PM48900008 PM 7880252 ER PT J AU LUNN, G RHODES, SW SANSONE, EB SCHMUFF, NR AF LUNN, G RHODES, SW SANSONE, EB SCHMUFF, NR TI PHOTOLYTIC DESTRUCTION AND POLYMERIC RESIN DECONTAMINATION OF AQUEOUS-SOLUTIONS OF PHARMACEUTICALS SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID DRUGS AB Amoxicillin, ampicillin, bleomycin, carmustine, cephalothin, dacarbazine, lomustine, metronidazole, norethindrone, streptozocin, sulfamethoxazole, and verapamil were completely degraded in solution, without the production of mutagenic residues, by photolysis using a medium-pressure mercury lamp in an all-quartz apparatus. A stream of air was passed through the solution and for amoxicillin, ampicillin, bleomycin, lomustine, metronidazole, and norethindrone it was necessary to add hydrogen peroxide. Dilute aqueous solutions of ampicillin, bleomycin, carmustine, cephalothin, lomustine, norethindrone, streptozocin, trimethoprim, and verapamil can be decontaminated using polymeric Amberlite resins. C1 US FDA,NLRC,ROCKVILLE,MD 20857. RP LUNN, G (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,POB B,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 50 TC 5 Z9 6 U1 2 U2 7 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 SEP PY 1994 VL 83 IS 9 BP 1289 EP 1293 DI 10.1002/jps.2600830920 PG 5 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA PF413 UT WOS:A1994PF41300019 PM 7830245 ER PT J AU NEGUS, SS BUTELMAN, ER CHANG, KJ DECOSTA, B WINGER, G WOODS, JH AF NEGUS, SS BUTELMAN, ER CHANG, KJ DECOSTA, B WINGER, G WOODS, JH TI BEHAVIORAL-EFFECTS OF THE SYSTEMICALLY ACTIVE DELTA-OPIOID AGONIST BW373U86 IN RHESUS-MONKEYS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID RECEPTOR SUBTYPES; MORPHINE-LIKE; DIFFERENTIAL ANTAGONISM; NUCLEUS-ACCUMBENS; OPIATE RECEPTORS; INDUCED SEIZURES; NALTRINDOLE; PEPTIDES; MICE; ANTINOCICEPTION AB The behavioral effects of (+/-)-4-((alpha R*)-alpha-((2S*,5R*)-4-allyl-2,5 -dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide dihydrochloride (BW373U86), a nonpeptidic, systemically active, delta opioid agonist, were examined in rhesus monkeys. BW373U86, the mu agonist alfentanil and the kappa agonist U69,593 {(5 alpha,7 alpha,8 beta)-(-)-N-methyl-N-(7-(1-pyrrolidinyl)-1-oxaspiro-(4,5)dec-8-yl)benzeneacetamide} all produced a dose-dependent suppression of response rates maintained under a fixed ratio 30 schedule of food presentation. The rate-suppressing effects of BW373U86 lasted 1 to 2 hr and were no longer apparent after 4 hr. The selective delta antagonist naltrindole (NTI) antagonized the effects of BW373U86 with relatively high potency (pK(B) = 6.5) and the antagonist effects of NTI against BW373U86 lasted approximately 4 hr. NTI was less potent in antagonizing alfentanil (pK(B) = 5.1) and the highest dose of NTI examined (10.0 mg/kg) did not antagonize U69,593. BW373U86 did not generalize to the discriminative stimulus effects of the mu agonist alfentanil or the kappa agonist ethylketocyclazacine. BW373U86 also did not produce antinociceptive effects in the warm-water tail-withdrawal procedure, significant respiratory depressant effects in monkeys breathing either air or 5% CO2 or reinforcing effects in a self-administration procedure. The highest dose of BW373U86 examined (1.78 mg/kg) produced convulsions in one monkey. The high relative potency of NTI to antagonize the rate-suppressing effects of BW373U86 was consistent with the characterization of BW373U86 as a systemically active, delta-selective agonist in rhesus monkeys. Under the conditions evaluated in the present study, the delta receptors to which BW373U86 binds do not appear to mediate antinociceptive, respiratory depressant or reinforcing effects in monkeys. C1 UNIV MICHIGAN,DEPT PHARMACOL,ANN ARBOR,MI 48109. BURROUGHS WELLCOME CO,RES TRIANGLE PK,NC 27709. NIDDKD,BETHESDA,MD 20892. FU NIDA NIH HHS [DA 00254] NR 57 TC 77 Z9 78 U1 0 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 SEP PY 1994 VL 270 IS 3 BP 1025 EP 1034 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PK968 UT WOS:A1994PK96800023 PM 7932149 ER PT J AU TERRY, P WITKIN, JM KATZ, JL AF TERRY, P WITKIN, JM KATZ, JL TI PHARMACOLOGICAL CHARACTERIZATION OF THE NOVEL DISCRIMINATIVE STIMULUS EFFECTS OF A LOW-DOSE OF COCAINE SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID DOPAMINE RECEPTOR AGONISTS; D-AMPHETAMINE; RHESUS-MONKEYS; MOLECULAR-CLONING; SQUIRREL-MONKEYS; RAT-BRAIN; QUINPIROLE; AFFINITY; EFFICACY; CUE AB Twelve rats were trained to press one lever after cocaine injection (3 mg/kg i.p.) and another lever after saline injection. Once rats were reliably discriminating cocaine from saline, other drugs were examined for their efficacies in substituting for cocaine. The dopamine uptake inhibitors WIN 35,428 [2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane-1,5-naphthalene-disulfonate] and GBR 12909 {1-[2-bis(4-fluorophenyl)methoxy]ethyl]-4-[3-phenylpropyl]piperazine dihydrochloride} fully substituted for cocaine (cocaine responding > 80%), whereas the peripherally active cocaine methiodide and the 5-hydroxytryptamine uptake inhibitor fluoxetine did not substitute at all. Pentobarbital also failed to produce any cocaine-appropriate responding. Two selective norepinephrine uptake inhibitors were tested: tomoxetine fully substituted for the 3-mg/kg dose of cocaine and nisoxetine approached full substitution (79.7% cocaine responding). The direct-acting dopamine D-1 agonists SKF 38393 [(+/-)-7-bromo-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine HCl], SKF 77434 [(+/-)-7,8-dihydroxy-3-allyl-1-phenyl-[2,3,4,5-tetrahydro-1H-benzazepine HCl] and SKF 75670 [3-methyl-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine HBr] fully substituted for cocaine, whereas the peripherally active dopamine D-1 agonist fenoldopam did not. Of four dopamine D-2 agonists tested, only quinpirole fully substituted; the others (N-0434 [(+/-)-2-(N-propyl-N-phenylethylamino)-5-hydroxytetralin], (-)-NPA [R(-)-propylnorapomorphine HCl] and SDZ 208-912 {N-[(8-)-2,6-dimethylergoline-8-yl]-2,2-dimethylpropanamide}) produced very limited partial substitution (cocaine responding < 32%). The results indicate that the 3 mg/kg of cocaine discriminative stimulus is centrally mediated and pharmacologically specific, but different from that produced by the more commonly used 10-mg/kg training dose. After training at 3 mg/kg of cocaine, there is an enhanced involvement of dopamine D-1 receptors in comparison with dopamine D-2 receptors. The results further suggest that not all dopamine D-2 agonists produce similar effects at a training dose of 3 mg/kg of cocaine. Finally, these results suggest an involvement of norepinephrine in the discriminative stimulus effects of low doses of cocaine. C1 NIDA,INTRAMURAL RES PROGRAM,PSYCHOBIOL SECT,BALTIMORE,MD 21224. OI Katz, Jonathan/0000-0002-1068-1159 NR 73 TC 96 Z9 97 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 1994 VL 270 IS 3 BP 1041 EP 1048 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PK968 UT WOS:A1994PK96800025 PM 7932151 ER PT J AU KARANIAN, JW KIM, HY SALEM, N AF KARANIAN, JW KIM, HY SALEM, N TI INHIBITORY EFFECTS OF N-6 AND N-3 HYDROXY FATTY-ACIDS ON THROMBOXANE (U46619)-INDUCED SMOOTH-MUSCLE CONTRACTION SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID DOCOSAHEXAENOIC ACID; LIPOXYGENASE; PROSTAGLANDIN-H2; METABOLISM; PLATELETS; PRODUCTS; 12-HETE AB Mammalian platelets are capable of enzymatically producing a number of n-6 and n-3 hydroxy fatty acids. Human platelet suspensions produce two major docosahexaenoic acid (22:6n3) metabolites, namely, 11-OH and 14-OH-22:6n3. The hydroxy fatty acids which were formed by human platelets and purified by high performance liquid chromatography specifically antagonize the contractile effects of a thromboxane mimetic, U46619, in airway, visceral and, especially, in the vascular smooth muscle preparations studied. The efficacy of OH-22:6n3 (IC25 = 1.1 mu M) was compared to other n-6 and n-3 hydroxy fatty acids in the rat aortic ring preparation. The OH-22:6n3 was significantly more potent with the exception of OH-22:5n3. The rank order of their potency was 14-OH-22:5n3 greater than or equal to 14-OH-22:6n3 > 17-OH-22:6n3 greater than or equal to 11-OH-22:6n3 greater than or equal to 11-OH-22:5n3 > 12-OH-20:5n3 greater than or equal to 12-OH-20:4n6 greater than or equal to 14-OH-22:5n6 > 13-OH-18:2n6 > 14-OH-22:5n5. Antagonism of thromboxane effects may be an important aspect of the biological function of 22-carbon n-3 hydroxylated fatty acids in platelet-vascular smooth muscle cell interactions. RP NIAAA, DICBR, MEMBRANE BIOCHEM & BIOPHYS LAB, BLDG 10 3C-102, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 26 TC 6 Z9 6 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 SEP PY 1994 VL 270 IS 3 BP 1105 EP 1109 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PK968 UT WOS:A1994PK96800033 PM 7932158 ER PT J AU RAPOPORT, SI AF RAPOPORT, SI TI IN-VIVO INCORPORATION OF LABELED LONG-CHAIN FATTY-ACIDS INTO BRAIN TO EXAMINE REGIONAL 2ND MESSENGER ACTIVATION AND NEUROPLASTICITY SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Meeting Abstract C1 NIA,NEUROSCI LAB,BETHESDA,MD 20892. NR 2 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD SEP PY 1994 VL 480P BP P16 EP P17 PG 2 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA PG781 UT WOS:A1994PG78100026 ER PT J AU PAIK, DI MOON, HS HOROWITZ, AM GIFT, HC JEONG, KL SUH, SS AF PAIK, DI MOON, HS HOROWITZ, AM GIFT, HC JEONG, KL SUH, SS TI KNOWLEDGE OF AND PRACTICES RELATED TO CARIES PREVENTION AMONG KOREANS SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article DE KNOWLEDGE OF CARIES PREVENTION; SOURCE OF ORAL HEALTH INFORMATION; HEALTH EDUCATION AND HEALTH PROMOTION; KOREAN ID ATTITUDES; HEALTH AB Objectives: This study assessed the knowledge and opinions of caries prevention and source of oral health information among Koreans. Methods: A questionnaire consisting of 36 items was used to interview 2,000 Koreans 10 through 69 years of age. Results for only selected questions are reported A multistage, stratified, random sampling method was used. Results: Sixty-nine percent of the respondents had heard about fluoride. Only 16 percent knew that some community water supplies in Korea are fluoridated. Fifty-five percent of respondents who knew about community water fluoridation learned the information from television, whereas 28 percent read about it in a newspaper. Among those respondents who reported hearing about community wafer fluoridation, only 30 percent had precise information about its purpose. Fifty-five percent of the respondents reported that toothbrushing is the best way to maintain good oral health. Almost all respondents (97 percent) reported brushing their teeth one of mote times a day. Conclusions: These data indicate that there is a relatively low level of accurate knowledge about dental caries prevention among Koreans 10 through 69 years of age. The majority of respondents report learning information about oral health from the mass media. C1 NIDR,EPIDEMIOL & ORAL DIS PREVENT PROGRAM,BETHESDA,MD 20892. SEOUL NATL UNIV,COLL DENT,DEPT PREVENT & PUBL HLTH DENT,SEOUL 110460,SOUTH KOREA. LUCKY LTD,LUCKY HOUSEHOLD GOODS RES INST,ORAL CARE LAB,CHUNGJU 360290,SOUTH KOREA. NR 32 TC 8 Z9 8 U1 0 U2 0 PU AAPHD NATIONAL OFFICE PI RICHMOND PA J PUBLIC HEALTH DENT 10619 JOUSTING LANE, RICHMOND, VA 23235 SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD FAL PY 1994 VL 54 IS 4 BP 205 EP 210 DI 10.1111/j.1752-7325.1994.tb01216.x PG 6 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA PJ693 UT WOS:A1994PJ69300003 PM 7799294 ER PT J AU KLEINMAN, DV AF KLEINMAN, DV TI BUILDING THE CAPACITY FOR THE RESPONSE OF THE DENTAL PROFESSION TO THE GLOBAL HIV PANDEMIC - A CASE-STUDY IN INTERNATIONAL COLLABORATION SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ORAL CANDIDIASIS; HAIRY LEUKOPLAKIA; INFECTION; ANTIBODIES; LESIONS; RISK; ASSOCIATION; SALIVA; AIDS RP KLEINMAN, DV (reprint author), NIDR,9000 ROCKVILLE PIKE,BLDG 31,BETHESDA,MD 20892, USA. NR 38 TC 0 Z9 0 U1 0 U2 0 PU AAPHD NATIONAL OFFICE PI RICHMOND PA J PUBLIC HEALTH DENT 10619 JOUSTING LANE, RICHMOND, VA 23235 SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD FAL PY 1994 VL 54 IS 4 BP 234 EP 237 DI 10.1111/j.1752-7325.1994.tb01222.x PG 4 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA PJ693 UT WOS:A1994PJ69300009 PM 7799299 ER PT J AU LAROSA, L MERONI, PL TINCANI, A BALESTRIERI, G FADEN, D LOJACONO, A MORASSI, L BROCCHI, E DELPAPA, N GHARAVI, A SAMMARITANO, L LOCKSHIN, M AF LAROSA, L MERONI, PL TINCANI, A BALESTRIERI, G FADEN, D LOJACONO, A MORASSI, L BROCCHI, E DELPAPA, N GHARAVI, A SAMMARITANO, L LOCKSHIN, M TI BETA(2)-GLYCOPROTEIN-I AND PLACENTAL ANTICOAGULANT PROTEIN-I IN PLACENTAE FROM PATIENTS WITH ANTIPHOSPHOLIPID-SYNDROME SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE ANTIPHOSPHOLIPID ANTIBODIES; PLACENTAL ANTICOAGULANT PROTEIN I; BETA 2 GLYCOPROTEIN I; RECURRENT FETAL LOSS ID SYSTEMIC LUPUS-ERYTHEMATOSUS; ANTICARDIOLIPIN ANTIBODIES; PHOSPHOLIPID BINDING; LIPOCORTIN FAMILY; BETA-2-GLYCOPROTEIN-I; PREGNANCY; CARDIOLIPIN; PLATELETS; INDUCTION; CRITERIA AB Objective. To investigate the immunohistological distribution of beta(2)-glycoprotein I (beta(2)GPI) and placental anticoagulant protein I (PAP-I) in normal and pathological placentae of patients with antiphospholipid (aPL) antibody associated recurrent fetal loss. These proteins are 2 natural anticoagulants able to interfere with aPL antibody binding. Methods. Placentae from 4 patients with primary antiphospholipid antibody syndrome (pAPS), from 2 patients with aPL negative systemic lupus erythematosus (SLE) and from 7 healthy women were studied. Cryostatic placental sections were tested by indirect immunofluorescence using polyclonal anti-PAP-I and anti-beta(2)GPI antisera as well as purified IgG and anti-beta(2)GPI monoclonal antibody. The same tissue sections were also tested by direct immunofluorescence with FITC-F(ab)(2) goat antihuman IgG. Results. We found that (a) the placental distribution of PAP-I was comparable in normal and pathological specimens; (b) on the contrary, increased beta(2)GPI deposition was present on the trophoblast surfaces of placentae obtained from patients with persistent raised titers of aPL antibodies. Comparable IgG deposition on villi surface was also found in aPL positive but not in control placentae. Conclusion. Our data are consistent with the hypothesis that high titer aPL binds to a beta(2)GPI phospholipid complex in placentae of women with recurrent fetal loss but that a quantitative deficiency of PAR-I does not play a pathogenetic role in aPL associated fetal loss. C1 UNIV MILAN,IST MED INTERNA MALATTIE INFETT & IMMUNOPATOL,SERV IMMUNOL CLIN,MILAN,ITALY. UNIV BRESCIA,SPEDALI CIVILI,IST ANAT PATOL,IST ZOOPROFILATTICO SPERIMENTALE,DEPT GYNECOL,BRESCIA,ITALY. LOUISIANA STATE UNIV,SCH MED,DEPT MED,NEW ORLEANS,LA. CORNELL UNIV,HOSP SPECIAL SURG,DEPT MED,NEW YORK,NY 10021. NIAMSD,BETHESDA,MD 20892. RI Tincani, Angela/E-7608-2010; Del Papa, Nicoletta/K-8513-2016 OI Del Papa, Nicoletta/0000-0003-1549-8852 FU NIAMS NIH HHS [AR32929] NR 47 TC 93 Z9 93 U1 0 U2 2 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD SEP PY 1994 VL 21 IS 9 BP 1684 EP 1693 PG 10 WC Rheumatology SC Rheumatology GA PF352 UT WOS:A1994PF35200020 PM 7799350 ER PT J AU MONDER, C MARSHALL, DE LAUGHLIN, LS BLYE, RP AF MONDER, C MARSHALL, DE LAUGHLIN, LS BLYE, RP TI STUDIES ON THE METABOLISM OF TESTOSTERONE TRANS-4-N-BUTYLCYCLOHEXANOIC ACID IN THE CYNOMOLGUS MONKEY, MACACA-FASCICULARIS SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article ID ACTING ANDROGEN ESTER; HORMONE ANTAGONIST; PHARMACOKINETICS; PHARMACODYNAMICS AB Metabolism of intravenously administered testosterone trans-4-n-butylcyclohexanoate (T bucyclate), a potent, long-acting androgen, was studied in cynomolgus monkeys (Macaca fascicularis). About 5% of the radioactivity of a dose of doubly labeled ester (C-14, H-3) was excreted via the gastrointestinal tract. Most of the administered radioactivity was excreted in the urine within 120 h. No intact T bucyclate was recovered from either compartment. Tritium attributed to bucyclic acid and its metabolites was excreted rapidly (peak excretion was at 6 h after injection), while C-14 excretion, attributed to testosterone and its metabolites, extended over 4 days. Testosterone metabolites were excreted predominantly as sulfate esters. Analysis of urinary products derived from the bucyclic acid moiety of T bucyclate showed no products susceptible to glucuronidase treatment, and showed a mixture of unidentified solvolyzable and unconjugated products. No unmetabolized trans-4-n-butylcyclohexanoic acid was detected in urine or feces. It is concluded that metabolism of testosterone bucyclate is initiated in vivo in cynomolgus monkeys by hydrolysis of ester to testosterone and bucyclic acid. The bucyclate side chain is rapidly cleared, and the testosterone is retained in the circulation. C1 UNIV CALIF DAVIS,CALIF REG PRIMATE RES CTR,DAVIS,CA 95616. NICHHD,CONTRACEPT DEV BRANCH,BETHESDA,MD 20852. RP MONDER, C (reprint author), POPULAT COUNCIL,1230 YORK AVE,NEW YORK,NY 10021, USA. FU NCRR NIH HHS [NICHD RR00169]; NICHD NIH HHS [N01-HD-9-2900] NR 8 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD SEP PY 1994 VL 50 IS 5-6 BP 305 EP 311 DI 10.1016/0960-0760(94)90136-8 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA PK521 UT WOS:A1994PK52100012 PM 7918117 ER PT J AU CASTON, JR BERENGUER, J KOCSIS, E CARRASCOSA, JL AF CASTON, JR BERENGUER, J KOCSIS, E CARRASCOSA, JL TI 3-DIMENSIONAL STRUCTURE OF DIFFERENT AGGREGATES BUILT-UP BY THE S-LAYER PROTEIN OF THERMUS-THERMOPHILUS SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article ID COLI OUTER MEMBRANES; 3-DIMENSIONAL STRUCTURE; ESCHERICHIA-COLI; CELL-ENVELOPE; SURFACE-LAYER; AEROMONAS-SALMONICIDA; BACTERIOPHAGE PHI-29; ELECTRON-MICROSCOPY; PORIN CHANNELS; NM RESOLUTION AB The 100-kDa S-layer protein from Thermus thermophilus HB8 is able to form three kinds of crystalline aggregates with different morphologies and symmetries when extracted from crude membranes using slightly different extractive procedures. Interestingly, only the structure showing P6 symmetry represents the native S-layer (called S1), while the others show a very different morphology. In this paper, the three dimensional structure of each of these crystals revealing their topographic features at 2-3 nm resolution has been analyzed by electron microscopy and image processing. The S1 crystals contain an hexagonal center, probably build up by six monomers, where most of the protein mass is concentrated. These P6 centers account for the width of the native S-layer, being the connective domains of the subunits (two per subunit) located at the outermost part of the structure. Such connections radiating from different P6 centers are mediated through centers with P3 symmetry. The other two crystals are also consistent with a lattice based on trimeric subunits probably related to those found in the connections between P6 centers of S1. The most conspicuous feature of these two latter forms is the presence of trimers of channels that traverse the crystal in the direction perpendicular to the plane of the membrane. Their distinct morphology, quite different from other S-layer assemblies, shows a surprising adaptive potential of this protein, and suggests interesting evolutive relationships to other membrane proteins. (C) 1994 Academic Press, Inc. C1 UNIV AUTONOMA MADRID,CSIC,CTR NACL BIOTECNOL,E-28049 MADRID,SPAIN. UNIV AUTONOMA MADRID,CSIC,CTR BIOL MOLEC,E-28049 MADRID,SPAIN. NIAMSD,STRUCT BIOL LAB,BETHESDA,MD 20892. RI Caston, Jose/L-5896-2014 OI Caston, Jose/0000-0003-2350-9048 NR 50 TC 9 Z9 9 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 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD SEP-OCT PY 1994 VL 113 IS 2 BP 164 EP 176 DI 10.1006/jsbi.1994.1049 PG 13 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA QH695 UT WOS:A1994QH69500008 PM 19634255 ER PT J AU SHRAYER, D BOGAARS, H GERSTEN, D HEARING, V MAIZEL, A WANEBO, H AF SHRAYER, D BOGAARS, H GERSTEN, D HEARING, V MAIZEL, A WANEBO, H TI NUDE-MOUSE MODEL TO STUDY PASSIVE HUMORAL IMMUNOTHERAPY DIRECTED AGAINST B16-F10 MURINE MELANOMA SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE NUDE MOUSE MODEL; HUMORAL IMMUNOTHERAPY; MURINE MELANOMA ID FORMALINIZED EXTRACELLULAR ANTIGENS; ANTIBODIES; MICE; VACCINE; CELLS; IMMUNIZATION; INHIBITION; INDUCTION; INVITRO; TUMORS AB A model to study passive humoral immunotherapy of experimental melanoma was generated by subcutaneous injection of B16 F10 murine melanoma cells in the midtail of BALB/C nude (nu/nu) mice. Mice were challenged with melanoma cells pretreated: (1) with complete culture medium, (2) with 10% adjuvant control serum, (3) with 10% anti-fECA (formalinized extracellular antigens) immune serum, or (4) with a monoclonal antibody (mAb H2-3-3) specific for the B700 melanoma-associated antigen. All control mice challenged with melanoma cells pretreated either with culture medium or with medium containing adjuvant control serum (Groups I and II) died during the observation period of 84 days. At day 84, 60% of the mice challenged with melanoma cells pretreated with anti-fECA immune serum (Group III) survived, as did 100% of the mice challenged with cells pretreated with mAb H2-3-3 (Group IV). Injection of melanoma cells pretreated with mAb H2-3-3 was associated with the greatest reduction of subsequent local tumor growth and the lowest number of metastatic lung tumors. The inhibitory effects of immune sera in vivo also correlated with in vitro effects of anti-fECA immune serum and mAb H2-3-3, determined on B16 F10 melanoma target cells using assays for DNA synthesis and antibody dependant cellular cytotoxicity (ADCC). In sum, this nude mouse model for the study of passive humoral immunotherapy of experimental melanoma was utilized to demonstrate significant protective effects against B16 F10 melanoma cell challenge by treatment with anti-fECA immune sera or a melanoma-specific monoclonal antibody. (C) 1994 Wiley-Liss, Inc. C1 BROWN UNIV,ROGER WILLIAMS MED CTR,DEPT SURG,PROVIDENCE,RI 02912. GEORGETOWN UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20007. NCI,CELL BIOL LAB,BETHESDA,MD 20892. RP SHRAYER, D (reprint author), BROWN UNIV,ROGER WILLIAMS MED CTR,DEPT PATHOL,825 CHALKSTONE AVE,PROVIDENCE,RI 02908, USA. NR 24 TC 2 Z9 2 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD SEP PY 1994 VL 57 IS 1 BP 50 EP 56 DI 10.1002/jso.2930570114 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA PD993 UT WOS:A1994PD99300014 PM 8065154 ER PT J AU BLACK, B UHDE, TW AF BLACK, B UHDE, TW TI TREATMENT OF ELECTIVE MUTISM WITH FLUOXETINE - A DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE ELECTIVE MUTISM; FLUOXETINE; ANXIETY; SOCIAL ANXIETY ID SOCIAL PHOBIA; MODIFIED CONNERS; ADOLESCENTS; PHENELZINE; CHILDREN; DISORDER; ANXIETY; TRIAL; MOOD AB Objective: To evaluate the efficacy of treatment with fluoxetine in reducing symptoms associated with elective mutism. Method: Sixteen subjects with elective mutism were treated with placebo (single-blind) for 2 weeks. Fifteen placebo nonresponders were then randomly assigned to double-blind treatment with fluoxetine at a dose of 0.6 mg/kg/day (N = 6) or continued placebo (N = 9) for an additional 12 weeks. Outcome ratings were completed by the treating psychiatrist, parents, and teachers. Results: Significant improvements over time on ratings of elective mutism, anxiety, and social anxiety, rated by clinician, parents, and teachers, were demonstrated in both fluoxetine- and placebo-treated subjects. Subjects treated with fluoxetine were significantly more improved than placebo-treated subjects on parent's ratings of mutism change and global change. Clinician and teacher ratings did not reveal significant differences between treatment groups. Although improved, most subjects in both treatment groups remained very symptomatic at the end of the study period. Side effects were minimal. Conclusion: Fluoxetine may be beneficial and safe in the treatment of children with elective mutism. Longer periods of treatment may yield more substantial therapeutic benefits. Further study is indicated. C1 TUFTS UNIV,SCH MED,BOSTON,MA 02111. NIMH,BIOL PSYCHIAT BRANCH,ANXIETY & AFFECT DISORDERS SECT,BETHESDA,MD 20892. WAYNE STATE UNIV,SCH MED,DEPT PSYCHIAT,DETROIT,MI 48201. RP BLACK, B (reprint author), TUFTS UNIV NEW ENGLAND MED CTR,DEPT PSYCHIAT,BOX 395,750 WASHINGTON ST,BOSTON,MA 02111, USA. NR 20 TC 161 Z9 162 U1 1 U2 6 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 1994 VL 33 IS 7 BP 1000 EP 1006 DI 10.1097/00004583-199409000-00010 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA PD466 UT WOS:A1994PD46600010 PM 7961338 ER PT J AU RAPOPORT, JL ELIA, J AF RAPOPORT, JL ELIA, J TI ADHD AND THE THYROID - REPLY SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Letter C1 MED COLL PENN,PHILADELPHIA,PA 19129. RP RAPOPORT, JL (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 1994 VL 33 IS 7 BP 1058 EP 1058 DI 10.1097/00004583-199409000-00019 PG 1 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA PD466 UT WOS:A1994PD46600019 ER PT J AU SHIOTA, T JONES, M TEIEN, D YAMADA, I PASSAFINI, A KNUDSON, O SAHN, DJ AF SHIOTA, T JONES, M TEIEN, D YAMADA, I PASSAFINI, A KNUDSON, O SAHN, DJ TI COLOR DOPPLER REGURGITANT JET AREA FOR EVALUATING ECCENTRIC MITRAL REGURGITATION - AN ANIMAL STUDY WITH QUANTIFIED MITRAL REGURGITATION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID PULMONARY VENOUS FLOW; ORIFICE SIZE; ECHOCARDIOGRAPHY; VARIABILITY; SEVERITY; MODEL AB Objectives. The purpose of the present study was to rigorously evaluate the accuracy of the color Doppler jet area planimetry method for quantifying chronic mitral regurgitation. Background. Although the color Doppler jet area has been widely used clinically for evaluating the severity of mitral regurgitation, there have been no studies comparing the color jet area with a strictly quantifiable reference standard for determining regurgitant volume. Methods. In six sheep with surgically produced chronic mitral regurgitation, 24 hemodynamically different states were obtained. Maximal color Doppler jet area for each state was obtained with a Vingmed 750. Image data were directly transferred in digital format to a microcomputer. Mitral regurgitation was quantified by the peak and mean regurgitant flow rates, regurgitant stroke volumes and regurgitant fractions determined using mitral and aortic electromagnetic how probes. Results. Mean regurgitant volumes varied from 0.19 to 2.4 liters/ min (mean [+/-SD] 1.2 +/- 0.59), regurgitant stroke volumes from 1.8 to 29 ml/beat (mean 11 +/- 6.2), peak regurgitant volumes from 1.0 to 8.1 liters/min (mean 3.5 +/- 2.1) and regurgitant fractions from 8.0% to 54% (mean 29 +/- 12%), Twenty-two of 24 jets were eccentric. Simple linear regression analysis between maximal color jet areas and peak and mean regurgitant flow rates, regurgitant stroke volumes and regurgitant fractions showed correlation, with r = 0.68 (SEE 0.64 cm(2)), r = 0.63 (SEE 0.67 cm(2)), r = 0.63 (SEE 0.67 cm(2)) and r = 0.58 (SEE 0.71 cm(2)), respectively. Univariate regression comparing regurgitant jet area with cardiac output, stroke volume, systolic left ventricular pressure, pressure gradient, left ventricular/left atrial pressure gradient, left atrial mean pressure, left atrial v wave pressure, systemic vascular resistance and maximal jet velocity showed poor correlation (0.08 < r < 0.53, SEE >0.76 cm(2)). Conclusions. This study demonstrates that color Doppler jet area has limited use for evaluating the severity of mitral regurgitation with eccentric jets. C1 OREGON HLTH SCI UNIV,CTR CLIN CARE CONGENITAL HEART DIS,PORTLAND,OR 97201. NHLBI,ANIM MED & SURG LAB,BETHESDA,MD 20892. FU NHLBI NIH HHS [HL 43287] NR 30 TC 26 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP PY 1994 VL 24 IS 3 BP 813 EP 819 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PH377 UT WOS:A1994PH37700033 PM 8077557 ER PT J AU CHOU, CL DIGIOVANNI, SR KNEPPER, MA AF CHOU, CL DIGIOVANNI, SR KNEPPER, MA TI HYDRO-OSMOTIC ACTION OF OXYTOCIN IN TERMINAL IMCD OF BRATTLEBORO RAT SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 268 EP 268 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77100096 ER PT J AU DIGIOVANNI, SR NIELSEN, S CHRISTENSEN, EI KNEPPER, MA AF DIGIOVANNI, SR NIELSEN, S CHRISTENSEN, EI KNEPPER, MA TI REGULATION OF EXPRESSION OF AQP-CD WATER CHANNEL BY VASOPRESSIN (AVP) IN BRATTLEBORO RATS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. AARHUS UNIV,DK-8000 AARHUS,DENMARK. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 269 EP 269 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77100099 ER PT J AU ECELBARGER, CA DIGIOVANNI, SR MAEDA, Y KNEPPER, MA AF ECELBARGER, CA DIGIOVANNI, SR MAEDA, Y KNEPPER, MA TI THE VASOPRESSIN (AVP) V2 RECEPTOR COUPLES TO 2 SIGNALING PATHWAYS IN RAT TERMINAL IMCD SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 269 EP 269 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77100100 ER PT J AU MAEDA, Y AGRE, P SMITH, BL KNEPPER, MA AF MAEDA, Y AGRE, P SMITH, BL KNEPPER, MA TI QUANTIFICATION OF AQUAPORIN-CHIP (AQP-CHIP) PROTEIN IN MICRODISSECTED TUBULES BY FLUORESCENCE-BASED ELISA SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. NHLBI,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 274 EP 274 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77100120 ER PT J AU MARPLES, D KNEPPER, MA CHRISTENSEN, EI NIELSEN, S AF MARPLES, D KNEPPER, MA CHRISTENSEN, EI NIELSEN, S TI VASOPRESSIN-INDUCED REDISTRIBUTION OF AQP-CD WATER CHANNELS IN RAT-KIDNEY INNER MEDULLA SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 AARHUS UNIV,DK-8000 AARHUS,DENMARK. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 275 EP 275 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77100122 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-INDUCED SHUTTLING OF AQP-CD WATER CHANNELS TO APICAL PLASMA-MEMBRANE IN ISOLATED-PERFUSED COLLECTING DUCTS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 AARHUS UNIV,DK-8000 AARHUS,DENMARK. NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 276 EP 276 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77100127 ER PT J AU CHATTON, JY SPRING, KR AF CHATTON, JY SPRING, KR TI THE SODIUM CONCENTRATION IN THE LATERAL INTERCELLULAR SPACES OF MDCK CELL MONOLAYERS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 283 EP 283 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77100152 ER PT J AU XIA, P PERSSON, BE SPRING, KR AF XIA, P PERSSON, BE SPRING, KR TI THE CHLORIDE CONCENTRATION IN THE LATERAL INTERCELLULAR SPACES OF MDCK CELL MONOLAYERS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,LKEM,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 304 EP 304 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77100234 ER PT J AU FERRARIS, JD WILLIAMS, CK MARTIN, BM BURG, MB GARCIAPEREZ, A AF FERRARIS, JD WILLIAMS, CK MARTIN, BM BURG, MB GARCIAPEREZ, A TI CLONING, GENOMIC ORGANIZATION, AND OSMOTIC RESPONSE OF THE ALDOSE REDUCTASE GENE SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 308 EP 308 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77100252 ER PT J AU KWON, ED ZABLOCKI, K JUNG, KY PETERS, EM GARCIAPEREZ, A BURG, MB AF KWON, ED ZABLOCKI, K JUNG, KY PETERS, EM GARCIAPEREZ, A BURG, MB TI OSMOREGULATION OF GPC-CHOLINE PHOSPHODIESTERASE (PDE) - DIFFERENT EFFECTS OF UREA AND NACL SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 312 EP 312 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77100266 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 EFFECT OF HIGH NACL AND UREA ON SYNTHESIS OF GLYCEROPHOSPHOCHOLINE (GPC) FROM PHOSPHATIDYLCHOLINE (PC) IN MDCK CELLS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NIAAA,ROCKVILLE,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 312 EP 312 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77100265 ER PT J AU SHEIKHHAMAD, D FERRARIS, JD BURG, MB GARCIAPEREZ, A AF SHEIKHHAMAD, D FERRARIS, JD BURG, MB GARCIAPEREZ, A TI DIFFERENTIAL DISPLAY AND CDNA CLONING OF HYPEROSMOTICALLY INDUCED MESSENGER-RNA FROM MDCK CELLS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,KIDNEY P ELECTROLYTE METAB LAB,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 320 EP 320 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77100298 ER PT J AU KOPPLE, JD CHUMLEA, WC GASSMAN, JJ HOLLINGER, DL MARONI, BJ MERRILL, D SCHERCH, LK SCHULMAN, G ZIMMER, GS AF KOPPLE, JD CHUMLEA, WC GASSMAN, JJ HOLLINGER, DL MARONI, BJ MERRILL, D SCHERCH, LK SCHULMAN, G ZIMMER, GS TI RELATIONSHIP BETWEEN GFR AND NUTRITIONAL-STATUS - RESULTS FROM THE MDRD STUDY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDKD,BETHESDA,MD. NR 0 TC 36 Z9 36 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 335 EP 335 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77100359 ER PT J AU KOPPLE, JD CHUMLEA, WC GASSMAN, JJ HOLLINGER, DL MARONI, BJ MERRILL, D SCHERCH, LK SCHULMAN, G ZIMMER, GS AF KOPPLE, JD CHUMLEA, WC GASSMAN, JJ HOLLINGER, DL MARONI, BJ MERRILL, D SCHERCH, LK SCHULMAN, G ZIMMER, GS TI NUTRITIONAL RESPONSE TO DIET PRESCRIPTION IN THE MDRD STUDY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract RP KOPPLE, JD (reprint author), NIDDKD,BETHESDA,MD, USA. NR 0 TC 36 Z9 36 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 335 EP 335 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77100358 ER PT J AU LEVEY, AS BECK, GJ CAGGIULA, AW GREENE, T KUSEK, JW STRIKER, GE KLAHR, S AF LEVEY, AS BECK, GJ CAGGIULA, AW GREENE, T KUSEK, JW STRIKER, GE KLAHR, S TI TRENDS TOWARD A BENEFICIAL EFFECT OF A LOW-PROTEIN DIET DURING ADDITIONAL FOLLOW-UP IN THE MODIFICATION OF DIET IN RENAL-DISEASE STUDY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDKD,BETHESDA,MD. NR 1 TC 3 Z9 3 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 336 EP 336 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77100363 ER PT J AU PETERSON, JC GREENE, T KLAHR, S BURKART, JM HEBERT, LA KING, AJ MASSRY, SG SEIFTER, JL AF PETERSON, JC GREENE, T KLAHR, S BURKART, JM HEBERT, LA KING, AJ MASSRY, SG SEIFTER, JL TI EFFECT OF REDUCING PROTEINURIA (PR) ON SUBSEQUENT GLOMERULAR-FILTRATION RATE (GFR) DECLINE IN PATIENTS WITH CHRONIC-RENAL-FAILURE (CRF) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDKD,BETHESDA,MD. NR 0 TC 3 Z9 3 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 339 EP 339 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77100376 ER PT J AU AUSTIN, HA BOUMPAS, DT VAUGHAN, EM BALOW, JE AF AUSTIN, HA BOUMPAS, DT VAUGHAN, EM BALOW, JE TI IMPORTANCE OF RACE AND CLINICAL AND HISTOLOGICAL FACTORS IN 1 66 PATIENTS WITH LUPUS NEPHRITIS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 346 EP 346 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77100403 ER PT J AU EKNOYAN, G BECK, GJ BREYER, JA KOPPLE, JD KUSEK, JW LEVEY, AS STRIKER, GE AF EKNOYAN, G BECK, GJ BREYER, JA KOPPLE, JD KUSEK, JW LEVEY, AS STRIKER, GE TI DESIGN AND PRELIMINARY-RESULTS OF THE MORTALITY AND MORBIDITY OF HEMODIALYSIS (MMHD) PILOT-STUDY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 513 EP 513 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101070 ER PT J AU LEVIN, NW AGODOA, LY GASSMAN, JJ HEYKA, RJ KAUFMAN, AM KEEN, ML AF LEVIN, NW AGODOA, LY GASSMAN, JJ HEYKA, RJ KAUFMAN, AM KEEN, ML TI COMPARISONS OF SMYE ALGORITHM WITH DOUBLE POOL MODEL SOLUTION FOR ESTIMATING E(KT/V) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD. NR 0 TC 3 Z9 3 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 519 EP 519 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101093 ER PT J AU SCHULMAN, G GOTCH, FA GREENE, T KESHAVIAH, P MASSRY, SG MEYER, KB AF SCHULMAN, G GOTCH, FA GREENE, T KESHAVIAH, P MASSRY, SG MEYER, KB TI VARIABILITY OF WHOLE-BODY UREA TRANSFER-COEFFICIENT (KC) IN THE MORTALITY AND MORBIDITY IN HEMODIALYSIS PILOT-STUDY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 528 EP 528 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101128 ER PT J AU BREYER, JA TOTO, RD HALL, WD NORRIS, KC MASSRY, SG AF BREYER, JA TOTO, RD HALL, WD NORRIS, KC MASSRY, SG TI BASE-LINE CHARACTERISTICS OF PATIENTS ENTERING THE PILOT AFRICAN-AMERICAN STUDY OF KIDNEY-DISEASE (PILOT-AASK) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 557 EP 557 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101245 ER PT J AU CAMPESE, VM TAWADROUS, M CHERVU, I GOLDSTEIN, D AF CAMPESE, VM TAWADROUS, M CHERVU, I GOLDSTEIN, D TI URINARY CATECHOLAMINES IN BLACK SALT-SENSITIVE (SS) PATIENTS WITH ESSENTIAL-HYPERTENSION (EH) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV SO CALIF,DIV NEPHROL,LOS ANGELES,CA 90089. NIH,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 558 EP 558 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101248 ER PT J AU WHELTON, P LEE, J KOPPLE, J FAULKNER, M CHARLESTON, J AF WHELTON, P LEE, J KOPPLE, J FAULKNER, M CHARLESTON, J TI RECRUITMENT IN THE AFRICAN-AMERICAN STUDY OF KIDNEY-DISEASE AND HYPERTENSION (AASK) PILOT-STUDY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDKD,BETHESDA,MD. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 570 EP 570 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101296 ER PT J AU WRIGHT, JT KIRK, KA KUSEK, J RANDALL, OS GLASSOCK, R AF WRIGHT, JT KIRK, KA KUSEK, J RANDALL, OS GLASSOCK, R TI THE DESIGN OF THE AFRICAN-AMERICAN STUDY OF KIDNEY-DISEASE AND HYPERTENSION (AASK) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD. NR 0 TC 3 Z9 3 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 570 EP 570 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101297 ER PT J AU ABASSI, ZA PIERUZZI, F CALIS, K KLEIN, H KEISER, HR AF ABASSI, ZA PIERUZZI, F CALIS, K KLEIN, H KEISER, HR TI EFFECTS OF CYCLOSPORINE ON THE CLEARANCE OF LABELED ENDOTHELIN IN RATS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NIH,DIC,DEPT PHARM,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 598 EP 598 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101410 ER PT J AU ABASSI, ZA KOTOB, SI GOLOMB, E KEISER, HR AF ABASSI, ZA KOTOB, SI GOLOMB, E KEISER, HR TI PULMONARY AND RENAL NEUTRAL ENDOPEPTIDASE 24.11 IN RATS WITH CONGESTIVE-HEART-FAILURE SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. US FDA,ROCKVILLE,MD 20857. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 599 EP 599 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101411 ER PT J AU HE, CJ ZALUPS, RK HENDERSON, DA YANG, CW STRIKER, GE STRIKER, LJ AF HE, CJ ZALUPS, RK HENDERSON, DA YANG, CW STRIKER, GE STRIKER, LJ TI SELECTIVE UP-REGULATION OF EXTRACELLULAR-MATRIX COMPONENTS (ECM) IN A GENETIC MODEL OF GLOMERULOSCLEROSIS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD. MERCER UNIV,SCH MED,MACON,GA 31207. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 624 EP 624 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101513 ER PT J AU ONUCHIC, L QIAN, F WEINSTATSASLOW, D BARTON, N SCHNEIDER, M SOMIO, S WATNICK, T REEDERS, S GERMINO, G AF ONUCHIC, L QIAN, F WEINSTATSASLOW, D BARTON, N SCHNEIDER, M SOMIO, S WATNICK, T REEDERS, S GERMINO, G TI DOES THE PKD1 GENE MAP TO A RENAL GENE-CLUSTER SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. NCI,BETHESDA,MD 20892. YALE UNIV,HHMI,NEW HAVEN,CT 06520. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. YESHIVA UNIV ALBERT EINSTEIN COLL MED,BRONX,NY 10461. RI Onuchic, Luiz/H-1589-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 633 EP 633 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101547 ER PT J AU AHUJA, SS BALOW, JE BOUMPAS, DT AF AHUJA, SS BALOW, JE BOUMPAS, DT TI TRANSCRIPTIONAL REGULATION OF TRANSFORMING GROWTH FACTOR-BETA(1) (TGF-BETA(1)) PROMOTER BY CALCINEURIN SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 687 EP 687 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101761 ER PT J AU BOTTINGER, EP FACTOR, V TSANG, MLS WEATHERBEE, JA QIAN, SW FAROKHZAD, OC WAKEFIELD, LM THORGEIRRYTHORGEIRSSON, SS KOPP, JB ROBERTS, AB SPORN, MB AF BOTTINGER, EP FACTOR, V TSANG, MLS WEATHERBEE, JA QIAN, SW FAROKHZAD, OC WAKEFIELD, LM THORGEIRRYTHORGEIRSSON, SS KOPP, JB ROBERTS, AB SPORN, MB TI THE RECOMBINANT PROREGION (HTGF-BETA-1 LAP) OF TRANSFORMING GROWTH-FACTOR-BETA-1 (TGF-BETA-1) MODULATES ITS ACTIVITY IN-VITRO AND IN-VIVO SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. NIDR,DEPT ORAL MED,BETHESDA,MD 20892. R&D SYST INC,MINNEAPOLIS,MN. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 689 EP 689 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101769 ER PT J AU LANDAU, D CHIN, E FLYBJERG, A ROBERTS, CT BONDY, C LEROITH, D AF LANDAU, D CHIN, E FLYBJERG, A ROBERTS, CT BONDY, C LEROITH, D TI EXPERIMENTAL DIABETES-MELLITUS (DM) INDUCES REGION-SPECIFIC CHANGES IN RENAL IGF SYSTEM SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,DB,BETHESDA,MD. NICHHD,DEB,BETHESDA,MD. CHILDRENS HOSP,NATL MED CTR,DEPT NEPHROL,WASHINGTON,DC 20010. AARHUS UNIV,INST EXPTL CLIN RES,DK-8000 AARHUS,DENMARK. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 696 EP 696 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101798 ER PT J AU LINDER, CY STRIKER, LJ HE, CJ LIU, ZH PETEN, EP STRIKER, GE AF LINDER, CY STRIKER, LJ HE, CJ LIU, ZH PETEN, EP STRIKER, GE TI EXPRESSION OF THE WILMS-TUMOR (WT1) SUPPRESSOR GENE IN THE ADULT-MOUSE KIDNEY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 697 EP 697 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101801 ER PT J AU KISHORE, BK KNEPPER, MA AF KISHORE, BK KNEPPER, MA TI EXTRACELLULAR NUCLEOTIDE RECEPTOR MEDIATES INHIBITION OF AVP-STIMULATED OSMOTIC WATER PERMEABILITY IN TERMINAL INNER MEDULLARY COLLECTING DUCT SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 719 EP 719 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101888 ER PT J AU FENG, L XIA, Y YOSHIMURA, T WILSON, CB AF FENG, L XIA, Y YOSHIMURA, T WILSON, CB TI ANTIMACROPHAGE INFLAMMATORY PROTEIN-2 (MIP-2) ANTIBODY (AB) MODULATES AB-INDUCED GLOMERULAR NEUTROPHIL INFLUX SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 Scripps Res Inst, RES INST, LA JOLLA, CA 92037 USA. NCI, FCRDC, FREDERICK, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 746 EP 746 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77101996 ER PT J AU LIU, ZH STAHL, PD STRIKER, LJ PATEL, A HE, CJ PONTOW, S STRIKER, GE AF LIU, ZH STAHL, PD STRIKER, LJ PATEL, A HE, CJ PONTOW, S STRIKER, GE TI INTERLEUKIN-1-ALPHA AND TUMOR-NECROSIS-FACTOR-ALPHA INDUCE MANNOSE RECEPTOR EXPRESSION IN GLOMERULAR MESANGIAL CELLS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,RENAL CELL BIOL SECT,BETHESDA,MD. WASHINGTON UNIV,SCH MED,ST LOUIS,MO 63110. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 756 EP 756 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77102037 ER PT J AU HANSS, BG BRUGGEMAN, LA COPELAND, T RAPPAPORT, J KLOTMAN, P AF HANSS, BG BRUGGEMAN, LA COPELAND, T RAPPAPORT, J KLOTMAN, P TI PURIFICATION OF A DNA-BINDING PROTEIN FROM RENAL BRUSH-BORDER MEMBRANE SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. NCI,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 780 EP 780 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77102133 ER PT J AU KOPP, JB NAGY, P SANDERSON, N WAKEFIELD, L BOTTINGER, EP ROBERTS, AB SPORN, MB THORGEIRSSON, SS KLOTMAN, PE AF KOPP, JB NAGY, P SANDERSON, N WAKEFIELD, L BOTTINGER, EP ROBERTS, AB SPORN, MB THORGEIRSSON, SS KLOTMAN, PE TI CIRCULATING TGF-BETA-1 AND RENAL-DISEASE IN TRANSGENIC MICE SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDR,LOM,BETHESDA,MD 20892. NCI,LCP,BETHESDA,MD 20892. NCI,LEC,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 785 EP 785 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77102154 ER PT J AU YANG, CW STRIKER, GE CHEN, WY CHEN, NY PETEN, EP KOPCHICK, JJ STRIKER, LJ AF YANG, CW STRIKER, GE CHEN, WY CHEN, NY PETEN, EP KOPCHICK, JJ STRIKER, LJ TI GLOMERULAR-ALPHA-1IV COLLAGEN AND TGF-BETA-1 MESSENGER-RNA ARE MARKERS OF PROGRESSIVE GLOMERULOSCLEROSIS - STUDIES IN MICE TRANSGENIC FOR NATIVE OR MUTATED GROWTH-HORMONE SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,RCBS,BETHESDA,MD. OHIO UNIV,DZ EABC,ATHENS,OH 45701. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 798 EP 798 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77102204 ER PT J AU HE, CJ STRIKER, LJ STRIKER, GE AF HE, CJ STRIKER, LJ STRIKER, GE TI MESANGIAL CELL-PROLIFERATION AND COLLAGEN MESSENGER-RNA LEVELS ARE INDEPENDENTLY REGULATED SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,MDB,RENAL CELL BIOL SECT,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 807 EP 807 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77102241 ER PT J AU MCGOWAN, KA KLEINMAN, HK SCHNAPER, HW AF MCGOWAN, KA KLEINMAN, HK SCHNAPER, HW TI EXPRESSION OF MESSENGER-RNA FOR EXTRACELLULAR-MATRIX (ECM) PROTEASES AND THEIR INHIBITORS BY MIGRATING ENDOTHELIAL-CELLS - AUGMENTATION OF RESPONSES BY ESTROGEN SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. NORTHWESTERN UNIV,SCH MED,DEPT PEDIAT,CHICAGO,IL 60611. NR 1 TC 2 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 813 EP 813 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77102266 ER PT J AU TAKAMI, H GAO, L HASSELL, JR YAMADA, Y AF TAKAMI, H GAO, L HASSELL, JR YAMADA, Y TI PERLECAN GENE TARGETING IN MOUSE EMBRYONIC STEM (ES) CELLS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDR,LDB,BETHESDA,MD 20892. UNIV PITTSBURGH,DEPT OPHTHALMOL,PITTSBURGH,PA 15260. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 820 EP 820 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77102292 ER PT J AU PETER, EP AF PETER, EP TI HIGH O2/O-BETA-IV COLLAGEN MESSENGER-RNA RATIO IN GLOMERULI ISOLATED FROM KIDNEY BIOPSIES WITH ESTABLISHED GLOMERULOSCLEROSIS (GS) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,MDB,RCBS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 837 EP 837 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77102362 ER PT J AU LIU, ZH STRIKER, LJ YANG, CW PETEN, EP STRIKER, GE AF LIU, ZH STRIKER, LJ YANG, CW PETEN, EP STRIKER, GE TI LOCALIZATION OF GLUTAMIC-ACID DECARBOXYLASE IN THE KIDNEYS OF NONOBESE DIABETIC (NOD) MICE SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,RENAL CELL BIOL SECT,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 968 EP 968 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77102884 ER PT J AU VANLIEW, LB YANG, CW STRIKER, LJ FELD, LG AF VANLIEW, LB YANG, CW STRIKER, LJ FELD, LG TI RESISTANCE TO GLOMERULOSCLEROSIS IN BIOBREEDING RATS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 SUNY BUFFALO,BUFFALO,NY 14260. CHILDRENS HOSP,DEPT PEDIAT & PHYSIOL,BUFFALO,NY 14222. VET ADM MED CTR,BUFFALO,NY 14215. NIDDK,BETHESDA,MD. NR 0 TC 3 Z9 3 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 973 EP 973 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77102904 ER PT J AU YANG, CW HATTORI, M VLASSARA, H HE, CJ STRIKER, GE STRIKER, LJ AF YANG, CW HATTORI, M VLASSARA, H HE, CJ STRIKER, GE STRIKER, LJ TI OVEREXPRESSION OF TGF-BETA-1 MESSENGER-RNA IS ASSOCIATED WITH UP-REGULATION OF GLOMERULAR TENASCIN AND LAMININ GENE-EXPRESSION IN DIABETIC NOD MICE SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,RCBS,BETHESDA,MD. JOSLIN DIABET CTR,SII,BOSTON,MA. PICOWER INST MED RES,NEW YORK,NY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 975 EP 975 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77102911 ER PT J AU SHRIVASTAV, S AHUJA, SS BALOW, JE BOUMPAS, DT AF SHRIVASTAV, S AHUJA, SS BALOW, JE BOUMPAS, DT TI CYCLOSPORINE-A (CSA) ENHANCES TRANSFORMING GROWTH-FACTOR-BETA (TGF-BETA) RECEPTOR EXPRESSION IN HUMAN T-LYMPHOCYTES SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1994 VL 5 IS 3 BP 989 EP 989 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PG771 UT WOS:A1994PG77102968 ER PT J AU YOSHIMURA, N WHITE, G WEIGHT, FF DEGROAT, WC AF YOSHIMURA, N WHITE, G WEIGHT, FF DEGROAT, WC TI PATCH-CLAMP RECORDINGS FROM SUBPOPULATIONS OF AUTONOMIC AND AFFERENT NEURONS IDENTIFIED BY AXONAL TRACING TECHNIQUES SO JOURNAL OF THE AUTONOMIC NERVOUS SYSTEM LA English DT Note DE PATCH-CLAMP; AXONAL TRACING; FAST BLUE; FLUOROGOLD; DORSAL ROOT GANGLION; MAJOR PELVIC GANGLION; TRIGEMINAL GANGLION ID CERVICAL-GANGLION NEURONS; MAJOR PELVIC GANGLION; ELECTROPHYSIOLOGICAL PROPERTIES; RAT; CURRENTS; CELLS; BLADDER; SODIUM; COLON AB This study determined whether axonal tracing methods can be used in combination with patch-clamp techniques to examine the electrical properties of identified populations of autonomic and afferent neurons in the adult rat. Fluorescent dyes (Fast Blue, FB and Fluoro-Gold, FG) were injected into the wall of the urinary bladder or colon and into various somatic structures to label postganglionic neurons in the major pelvic ganglia (MPG) as well as visceral and somatic afferent neurons in the lumbosacral dorsal root ganglia (DRG) and trigeminal ganglia (TG). One to 3 weeks after dye injection, neurons were isolated from ganglia by enzymatic dissociation. Following dissociation, single neurons labelled with FB were identified in the three types of ganglion preparations; however FG was only identified consistently in TG neurons. FB was retained in neurons during short-term culture (1-5 days). Following 10 to 20 s exposure to UV light which was required for identification of the cells, whole-cell patch-clamp recordings revealed that the electrophysiological properties of FB-labelled cells did not differ from those of unlabelled cells. However, a more prolonged exposure (1-5 min) of the neurons to UV light produced irreversible damage to the cells which was evident as changes in the action potential, sodium current and resting membrane potential. These results indicate that patch-clamp recording in combination with axonal tracing is a useful approach for studying the electrical properties of identified populations of autonomic and afferent neurons. Preliminary data indicate that small diameter bladder and colon afferent neurons have similar electrophysiological properties and that these properties are very different from those of large diameter somatic afferent neurons. C1 NIAAA,PHYSIOL & PHARMACOL STUDIES LAB,ELECTROPHYSIOL SECT,ROCKVILLE,MD 20852. RP YOSHIMURA, N (reprint author), UNIV PITTSBURGH,SCH MED,DEPT PHARMACOL,E1303 BIOMED SCI TOWER,PITTSBURGH,PA 15261, USA. NR 22 TC 28 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-1838 J9 J AUTONOM NERV SYST JI J. Auton. Nerv. Syst. PD SEP PY 1994 VL 49 IS 1 BP 85 EP 92 DI 10.1016/0165-1838(94)90024-8 PG 8 WC Neurosciences SC Neurosciences & Neurology GA NY374 UT WOS:A1994NY37400010 PM 7963269 ER PT J AU REEPMEYER, JC RHODES, MO COX, DC SILVERTON, JV AF REEPMEYER, JC RHODES, MO COX, DC SILVERTON, JV TI CHARACTERIZATION AND CRYSTAL-STRUCTURE OF 2 POLYMORPHIC FORMS OF RACEMIC THALIDOMIDE SO JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2 LA English DT Article ID VERSUS-HOST DISEASE; GRAFT-SURVIVAL; MODEL AB There are two polymorphic forms of racemic thalidomide. The alpha-polymorph was formed by crystallization from 2-ethoxyethanol, methanol or dichloromethane, while the beta-polymorph was formed by crystallization from a supersaturated solution in refluxing 2-ethoxyethanol. The two polymorphs were characterized by IR spectra, differential scanning calorimetry (DSC). melting points, powder X-ray diffraction patterns, and X-ray crystallography. They were easily differentiated by IR (KBr) in which the alpha polymorph absorbed at 3196, 3098 and 859 cm(-1) and the beta at 3276 and 755 cm(-1). DSC scans of the alpha and beta forms showed endothermic peaks at 272.3 and 275.7 degrees C, respectively. During this measurement the alpha form was partially or fully converted into the beta form if the rate of temperature change was slow or if the alpha form contained some beta which provided seed crystals for the interconversion. Upon remelting both forms gave one peak corresponding to the beta polymorph. The powder X-ray diffraction patterns for the two forms differ significantly. The crystal structures of the two polymorphs differ primarily in their mode of hydrogen bonding. In the alpha polymorph the molecules form dimers, while in the beta the dimers form infinite linear strings linked by bifurcated hydrogen bonds along the b-axis. C1 NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. RP REEPMEYER, JC (reprint author), US FDA,DIV DRUG ANAL,1114 MARKET ST,ST LOUIS,MO 63101, USA. NR 20 TC 11 Z9 11 U1 3 U2 7 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK MILTON ROAD, CAMBRIDGE, CAMBS, ENGLAND CB4 4WF SN 0300-9580 J9 J CHEM SOC PERK T 2 JI J. Chem. Soc.-Perkin Trans. 2 PD SEP PY 1994 IS 9 BP 2063 EP 2067 DI 10.1039/p29940002063 PG 5 WC Chemistry, Organic; Chemistry, Physical SC Chemistry GA PF418 UT WOS:A1994PF41800026 ER PT J AU NUSSBAUM, O BRODER, CC BERGER, EA AF NUSSBAUM, O BRODER, CC BERGER, EA TI FUSOGENIC MECHANISMS OF ENVELOPED-VIRUS GLYCOPROTEINS ANALYZED BY A NOVEL RECOMBINANT VACCINIA VIRUS-BASED ASSAY QUANTITATING CELL FUSION-DEPENDENT REPORTER GENE ACTIVATION SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; BACTERIOPHAGE-T7 RNA-POLYMERASE; NUCLEOTIDE-SEQUENCE; BETA-GALACTOSIDASE; T-CELL; CD4-MEDIATED FUSION; MURINE CELLS; AIDS VIRUS; EXPRESSION; TYPE-1 AB The fusogenic activities of enveloped-virus glycoproteins were analyzed by using a quantitative, sensitive, rapid, and highly versatile recombinant vaccinia virus-based assay measuring activation of a reporter gene upon fusion of two distinct cell populations. One population uniformly expressed vaccinia virus-encoded viral glycoproteins mediating specific binding and fusion activities; the other expressed the corresponding cellular receptor(s). The cytoplasm of one population also contained vaccinia virus-encoded bacteriophage T7 RNA polymerase; the cytoplasm of the other contained a transfected plasmid with the Escherichia coli lacZ gene linked to the T7 promoter. When the two populations were mixed, cell fusion resulted in activation of the LacZ gene in the cytoplasm of the fused cells; beta-galactosidase activity was assessed by colorimetric assay of detergent cell lysates or by in situ staining. We applied this approach to study the human immunodeficiency virus type 1 envelope glycoprotein (Env)-CD4 interaction. beta-Galactosidase was detected within 1 h after cell mixing and accumulated over the next several hours. Cell fusion dependence was demonstrated by the strict requirement for both CD4 and functional Env expression and by the inhibitory effects of known fusion-blocking monoclonal antibodies and pharmacological agents. Quantitative measurements indicated much higher sensitivity compared with analysis of syncytium formation. The assay was used to probe mechanisms of the cell type specificity for Env-CD4-mediated fusion. In agreement with known restrictions, cell fusion occurred only when CD4 was expressed on a human cell type. Membrane vesicle transfer experiments indicated that CD4 initially produced in either human or nonhuman cells was functional when delivered to human cells, suggesting that the fusion deficiency with nonhuman cells was not associated with irreversible defects in CD4. We also demonstrated that the infectivity specificities of different human immunodeficiency virus type 1 isolates for peripheral blood lymphocytes versus continuous CD4(+) cell lines were associated with corresponding fusion selectivities of the respective recombinant Env proteins. The assay enabled analysis of the fusogenic activity of the fusion glycoprotein/hemagglutinin-neuraminidase of the paramyxovirus simian virus 5. This system provides a powerful tool to study fusion mechanisms mediated by enveloped-virus glycoproteins, as well as to screen fusion-blocking antibodies and pharmacological agents. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NR 46 TC 327 Z9 328 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1994 VL 68 IS 9 BP 5411 EP 5422 PG 12 WC Virology SC Virology GA PB785 UT WOS:A1994PB78500009 PM 8057423 ER PT J AU MICHELSON, S ALCAMI, J KIM, SJ DANIELPOUR, D BACHELERIE, F PICARD, L BESSIA, C PAYA, C VIRELIZIER, JL AF MICHELSON, S ALCAMI, J KIM, SJ DANIELPOUR, D BACHELERIE, F PICARD, L BESSIA, C PAYA, C VIRELIZIER, JL TI HUMAN CYTOMEGALOVIRUS-INFECTION INDUCES TRANSCRIPTION AND SECRETION OF TRANSFORMING GROWTH-FACTOR-BETA-1 SO JOURNAL OF VIROLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; TGF-BETA; FACTOR-BETA-1 GENE; EARLY PROTEIN; HUMAN LUNG; CELLS; FIBROBLASTS; EXPRESSION; ACTIVATION; INDUCTION AB Human cytomegalovirus (CMV) infection can elicit a transitory, but profound, immunodepression in immunocompetent individuals. Cytopathogenic destruction of CMV-infected leukocytes alone does not seem sufficient to explain this phenomenon, which suggests that immune system mediators (cytokines) may play a role in amplifying local modifications wrought by CMV infection. We reported previously that transforming growth factor beta 1 (TGF-beta 1) stimulates CMV replication (J.Alcami, C. V. Paya, J. L. Virelizier, and S. Michelson, J. Gen. Virol. 74:269-274, 1993). Since TGF-beta 1 can have profound negative effects on cell growth and immune responses, we investigated the induction of TGF-beta 1 following CMV infection of permissive fibroblasts. TGP-beta 1 promoter was activated by immediate-early (IE) proteins in the absence of infection and transactivated at 5 and 9 h after infection. TGF-beta 1 mRNA increased during the early phase of infection, suggesting that this phenomenon is due to enhanced transcription of the TGF-beta 1 gene. A comparative study of the influence of CMV infection and IE protein expression on TGF-beta 1 promoter function in permissive cells pointed to a possible cooperative role between IE proteins and protein(s) expressed during the early phase of viral infection. Induction of TGF-beta 1 by CMV infection could modify infected cells individually, surrounding tissues, and systemic immune reactions to the advantage of virus replication by both upregulating CMV replication and downregulating host immune responses. C1 NCI, CHEMOPREVENT LAB, BETHESDA, MD 20892 USA. RP MICHELSON, S (reprint author), INST PASTEUR, UNITE IMMUNOL VIRALE, 28 RUE DR ROUX, F-75724 PARIS 15, FRANCE. RI BACHELERIE, FRANCOISE/F-8823-2013 NR 50 TC 114 Z9 119 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1994 VL 68 IS 9 BP 5730 EP 5737 PG 8 WC Virology SC Virology GA PB785 UT WOS:A1994PB78500044 PM 8057454 ER PT J AU GIESE, NA GIESE, T MORSE, HC AF GIESE, NA GIESE, T MORSE, HC TI MURINE AIDS IS AN ANTIGEN-DRIVEN DISEASE - REQUIREMENTS FOR MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II EXPRESSION AND CD4+ T-CELLS SO JOURNAL OF VIROLOGY LA English DT Article ID RETROVIRUS-INDUCED IMMUNODEFICIENCY; DEFICIENT MICE; SYNDROME MAIDS; VIRUS; ACTIVATION; MOUSE; SUSCEPTIBILITY; LYMPHOCYTES; SELECTION; STRAINS AB Murine AIDS (MAIDS) is a complex syndrome of lymphoproliferation and immunodeficiency induced by a replication-defective murine leukemia virus (BM5def) that encodes Pr60(gag) as its only product. It has been suggested that the gag polyprotein is responsible for vigorous antigenic stimulation of CD4(+) T cells and generalized secondary activation of the immune system. This model was tested first by infecting mice (C2K/O) that lack class II major histocompatibility complex molecules required for presentation of antigens to CD4(+) T cells. C2K/O mice expressed BM5def at high levels but did not develop MAIDS either when unmanipulated or following transfer of CD4(+) T cells. Second, B6 mice reconstituted with C2K/O bone marrow cells had normal frequencies of B cells (class II negative) and CD4(+) cells and expressed high levels of BM5def transcripts but did not develop MAIDS; however, MAIDS developed in class II-competent nu/nu mice reconstituted with CD4(+) T cells and in C2K/O mice reconstituted with B6 bone marrow to give class II-positive B cells and with purified CD4(+) T cells. These results indicate that induction of MAIDS by BM5def is antigen driven and is dependent on expression of major histocompatibility complex class II molecules on antigen-presenting cells and the presence of CD4(+) T cells. C1 NCI,GENET LAB,BETHESDA,MD 20892. RP GIESE, NA (reprint author), NIAID,IMMUNOPATHOL LAB,BLDG 7,ROOM 302,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Morse, Herbert/0000-0002-9331-3705 FU NIAID NIH HHS [N01-AI-45203] NR 25 TC 41 Z9 41 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1994 VL 68 IS 9 BP 5819 EP 5824 PG 6 WC Virology SC Virology GA PB785 UT WOS:A1994PB78500054 PM 7914549 ER PT J AU KANG, CY HARIHARAN, K NARA, PL SODROSKI, J MOORE, JP AF KANG, CY HARIHARAN, K NARA, PL SODROSKI, J MOORE, JP TI IMMUNIZATION WITH A SOLUBLE CD4-GP120 COMPLEX PREFERENTIALLY INDUCES NEUTRALIZING ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ANTIBODIES DIRECTED TO CONFORMATION-DEPENDENT EPITOPES OF GP120 SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; GLYCOPROTEIN GP120; ENVELOPE GLYCOPROTEIN; BINDING; HIV-1; CD4; CHIMPANZEES; INFECTIVITY; REGION; GP160 AB Preservation of the conformation of recombinant gp120 in an adjuvant, enabling it to elicit conformation-dependent, epitope-specific, broadly neutralizing antibodies, may be critical for the development of any gpl20-based human immunodeficiency virus type 1 (HIV-1) vaccine. It was hypothesized that recombinant gp120 complexed with recombinant CD3 could stabilize the conformation-dependent neutralizing epitopes and effectively deliver them to the immune system. Therefore, a soluble CD4-gp120 complex in Syntex adjuvant formulation was tested with mice for its ability to induce neutralizing anti-gpl20 antibody responses. Seventeen monoclonal antibodies (MAbs) were generated and characterized. Immunochemical studies, neutralization assays, and mapping studies with gp120 mutants indicated that the 17 MAbs fell into three groups. Four of them were directed to what is probably a conformational epitope involving the C1 domain and did not possess virus-neutralizing activities. Another four MAbs bound to V3 peptide 302-321 and exhibited cross-reactive gp120 binding and relatively weak virus-neutralizing activities. These MAbs were very sensitive to amino acid substitutions, not only in the V3 regions but also in the base of the V1/V2 loop, implying a conformational constraint on the epitope. The last group of nine MAbs recognized conformation-dependent epitopes near the CD3 binding site of gp120 and inhibited the gp120-soluble CD4 interaction. Pour of these nine MAbs showed broadly neutralizing activities against multiple laboratory-adapted strains of HIV-1, three of them neutralized only HIVIIIB, and the two lower-affinity MAbs did not neutralize any strain tested. Collectively, the results from this study indicate that immunization with the CD4-gp120 complex can elicit antibodies to conformationally sensitive gp120 epitopes, with some of the antibodies having broadly neutralizing activities. We suggest that immunization with CD4-gp120 complexes may be worth evaluating further for the development of an AIDS vaccine. C1 IDEC PHARMACEUT CORP,SAN DIEGO,CA 92121. NCI,FREDERICK CANC RES & DEV CTR,VIRUS BIOL UNIT,FREDERICK,MD 21701. HARVARD UNIV,SCH MED,DEPT PATHOL,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. NYU,SCH MED,AARON DIAMOND AIDS RES CTR,NEW YORK,NY 10016. FU NIAID NIH HHS [AI31310, AI31783, AI36082] NR 50 TC 55 Z9 55 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1994 VL 68 IS 9 BP 5854 EP 5862 PG 9 WC Virology SC Virology GA PB785 UT WOS:A1994PB78500058 PM 7520095 ER PT J AU ENGELMAN, A HICKMAN, AB CRAIGIE, R AF ENGELMAN, A HICKMAN, AB CRAIGIE, R TI THE CORE AND CARBOXYL-TERMINAL DOMAINS OF THE INTEGRASE PROTEIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 EACH CONTRIBUTE TO NONSPECIFIC DNA-BINDING SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; HIV-1 INTEGRASE; ESCHERICHIA-COLI; INVITRO; IDENTIFICATION; REGION; SUBSTRATE; ENDONUCLEASE; MUTAGENESIS; SEQUENCES AB The integrase protein of human immunodeficiency virus type 1 removes two nucleotides from the 3' ends of reverse-transcribed human immunodeficiency virus type 1 DNA (3' processing) and covalently inserts the processed ends into a target DNA (DNA strand transfer). Mutant integrase proteins that lack the amino- and/or carboxyl-terminal domains are incapable of catalyzing 3' processing and DNA strand transfer but are competent for an apparent reversal of the DNA strand transfer reaction (disintegration) in vitro. Here, we investigate the binding of integrase to DNA by UV cross-linking. Cross-linked complexes form with a variety of DNA substrates independent of the presence of divalent metal ion. Analysis with amino- and carboxyl-terminal deletion mutant proteins shows that residues 213 to 266 of the 288-residue protein are required for efficient cross-linking in the absence of divalent metal ion. Carboxyl-terminal deletion mutants that lack this region efficiently cross-link only to the branched disintegration DNA substrate, and this reaction is dependent on the presence of metal ion. Both the core and C-terminal domains of integrase therefore contribute to nonspecific DNA binding. C1 NIDDK,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 40 TC 204 Z9 206 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1994 VL 68 IS 9 BP 5911 EP 5917 PG 7 WC Virology SC Virology GA PB785 UT WOS:A1994PB78500064 PM 8057470 ER PT J AU BROWN, EW YUHKI, N PACKER, C OBRIEN, SJ AF BROWN, EW YUHKI, N PACKER, C OBRIEN, SJ TI A LION LENTIVIRUS RELATED TO FELINE IMMUNODEFICIENCY VIRUS - EPIDEMIOLOGIC AND PHYLOGENETIC ASPECTS SO JOURNAL OF VIROLOGY LA English DT Article ID AFRICAN-GREEN MONKEYS; NUCLEOTIDE-SEQUENCE; GENETIC DIVERSITY; MOLECULAR EPIDEMIOLOGY; GENOME ORGANIZATION; NONDOMESTIC FELIDS; INFECTION; EVOLUTION; PROTEINS; ORIGINS AB Feline immunodeficiency virus (FIV) is a novel lentivirus that is genetically homologous and functionally analogous to the human AIDS viruses, human immunodeficiency virus types 1 and 2. FIV causes immunosuppression in domestic cats by destroying the CD4 T-lymphocyte subsets in infected hosts. A serological survey of over 400 free-ranging African and Asian lions (Panthera lee) for antibodies to FIV revealed endemic lentivirus prevalence with an incidence of seropositivity as high as 90%. A lion lentivirus (FIV-Ple) was isolated by infection of lion lymphocytes in vitro. Seroconversion was documented in two Serengeti lions, and discordance of mother-cub serological status argues against maternal transmission (in favor of horizontal spread) as a major route of infection among lions. A phylogenetic analysis of cloned FIV-Ple pol gene sequences from 27 lions from four African populations (from the Serengeti reserve, Ngorongoro Crater, Lake Manyara, and Kruger Park) revealed remarkably high intra- and interindividual genetic diversity at the sequence level. Three FIV-Ple phylogenetic clusters or clades were resolved with phenetic, parsimony, and likelihood analytical procedures. The three clades, which occurred not only together in the same population but throughout Africa, were as divergent from each other as were homologous pol sequences of lentivirus isolated from distinct feline species, i.e., puma and domestic cat. The FIV-Ple clades, however, were more closely related to each other than to other feline lentiviruses (monophyletic for lion species), suggesting that the ancestors of FIV-Ple evolved in allopatric (geographically isolated) lion populations that converged recently. To date, there is no clear evidence of FIV-Ple-associated pathology, raising the possibility of a historic genetic accommodation of the lion lentivirus and its host leading to a coevolved host-parasite symbiosis (or commensalism) in the population similar to that hypothesized for endemic simian immunodeficiency virus without pathology in free-ranging African monkey species. 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. UNIV MINNESOTA,DEPT ECOL EVOLUT & BEHAV,MINNEAPOLIS,MN 55455. NR 55 TC 97 Z9 97 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 SEP PY 1994 VL 68 IS 9 BP 5953 EP 5968 PG 16 WC Virology SC Virology GA PB785 UT WOS:A1994PB78500069 PM 8057472 ER PT J AU WANG, JX JIANG, X MADORE, HP GRAY, J DESSELBERGER, U ANDO, T SETO, Y OISHI, I LEW, JF GREEN, KY ESTES, M AF WANG, JX JIANG, X MADORE, HP GRAY, J DESSELBERGER, U ANDO, T SETO, Y OISHI, I LEW, JF GREEN, KY ESTES, M TI SEQUENCE DIVERSITY OF SMALL, ROUND-STRUCTURED VIRUSES IN THE NORWALK VIRUS GROUP SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNE ELECTRON-MICROSCOPY; CAPSID PROTEIN GENE; NUCLEOTIDE-SEQUENCE; FELINE CALICIVIRUS; SNOW MOUNTAIN; VIRAL GASTROENTERITIS; GENOME; ORGANIZATION; IMMUNOASSAY; SEROTYPES AB We have determined the nucleotide sequences of a highly conserved region of the RNA dependent RNA polymerase of the prototype Snow Mountain agent (SMA) and of four other small, round-structured viruses (antigenically Norwalk virus [NV]-like or SMA-like) following reverse transcription-PCR amplification of viral RNA obtained from human stools. The stool samples were either from volunteers administered SMA or from sporadic cases and outbreaks of gastroenteritis that occurred in Japan and the United Kingdom between 1984 and 1992. The GLPSG and YGDD RNA polymerase motifs were in the proper locations in the sequences of the five SRSVs, but each sequence was distinct from the 8FIIa prototype NV sequence and from each other. Analysis of the sequences and reactivities in a new NV antigen enzyme-linked immunosorbent assay showed that the five viruses could be divided into two groups (serogroups) with NV and SMA, respectively, being the prototypes. The sequences of the capsid region and a nonstructural region (2C) were determined from one strain from each group. One virus (SRSV-KY-89/89/J), isolated in Japan and antigenically similar to the prototype NV (isolated 21 years earlier in Ohio), showed a remarkable level of sequence similarity to NV. KY-89 and the 8FIIa NV shovved 87.2% nucleotide similarity over 2,516 continuous nucleotides amounting to 96 to 98.9% amino acid similarity in three distinct domains in two open reading frames. Between the prototype SMA and NV, the polymerase region showed 63% nucleotide and 59% amino acid similarity, respectively. Two other antigenically SMA-like isolates (SRSV-925/92/UK and SRSV-OTH-25/89/J), from the United Kingdom and Japan, showed 80% nucleotide and 88 to 92% amino acid similarity in the polymerase region to the prototype SMA isolated 16 and 13 years earlier in the United States. The capsid region of the antigenically SR SMA-like OTH-25 virus showed 53% nucleotide and 65% amino acid similarity to the prototype NV capsid region. Domains of sequence diversity and conservation were identified within the capsid protein of these two distinct prototype serotypes of virus. These results indicate that NV-like and SMA-like agents are still circulating, and sequence comparisons will be useful to identify and classify distinct viruses in the NV group. C1 BAYLOR COLL MED, DIV MOLEC VIROL, HOUSTON, TX 77030 USA. UNIV ROCHESTER, SCH MED & DENT, DEPT MED, ROCHESTER, NY 14642 USA. ADDENBROOKES HOSP, CLIN MICROBIOL & PUBL HLTH LAB, CAMBRIDGE CB2 2QW, ENGLAND. TOKYO METROPOLITAN RES LAB PUBL HLTH, DEPT VIROL, SHINJUKU KU, TOKYO 169, JAPAN. OSAKA CITY INST PUBL HLTH & ENVIRONM SCI, DEPT VIROL, OSAKA 543, JAPAN. OSAKA PREFECTURAL INST PUBL HLTH, VIROL LAB, HIGASHINARI KU, OSAKA 537, JAPAN. NIAID, INFECT DIS LAB, BETHESDA, MD 20892 USA. FU NIAID NIH HHS [AI30448] NR 34 TC 194 Z9 197 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1994 VL 68 IS 9 BP 5982 EP 5990 PG 9 WC Virology SC Virology GA PB785 UT WOS:A1994PB78500071 PM 8057474 ER PT J AU BOUHABIB, DC RODERIQUEZ, G ORAVECZ, T BERMAN, PW LUSSO, P NORCROSS, MA AF BOUHABIB, DC RODERIQUEZ, G ORAVECZ, T BERMAN, PW LUSSO, P NORCROSS, MA TI CRYPTIC NATURE OF ENVELOPE V3 REGION EPITOPES PROTECTS PRIMARY MONOCYTOTROPIC HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 FROM ANTIBODY NEUTRALIZATION SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNE-DEFICIENCY SYNDROME; AMINO-ACID SUBSTITUTION; CELL TROPISM; MONOCLONAL-ANTIBODIES; SOLUBLE CD4; BIOLOGICAL PHENOTYPE; GLYCOPROTEIN GP120; INFECTED HUMANS; HIV-1; DOMAIN AB Characterization of biological and immunological properties of human immunodeficiency virus type 1 (HIV-1) is critical to developing effective therapies and vaccines for AIDS. With the use of a novel CD4(+) T-cell line (PM-1) permissive to infection by both monocytotropic (MT) and T-cell-tropic virus types, we present a comparative analysis of the immunological properties of a prototypic primary MT isolate of HIV-1 strain JR-CSF (MT-CSF) with those of a T-cell-tropic variant (T-CSF) of the same virus, which emerged spontaneously in vitro. The parental MT-CSF infected only PM-1 cells and was markedly resistant to neutralization by sera from HIV-1-infected individuals, rabbit antiserum to recombinant MT-CSF gp120, and anti-V3 monoclonal antibodies. The T-CSF variant infected a variety of CD4(+) T-cell lines, contained positively charged amino acid substitutions in the gp120 V3 region, and was highly sensitive to antibody neutralization. Neutralization and antibody staining of T-CSF-expressing cells were significantly inhibited by HIV-1 V3 peptides; in contrast, the MT strain showed only weak V3-specific binding of polyclonal and monoclonal antibodies. Exposure of PM-1 cells to a mixture of both viruses in the presence of human anti-HIV-1 neutralizing antiserum resulted in infection with only MT-CSF. These results demonstrate that although the V3 region of MT viruses is immunogenic, the target epitopes in the V3 principal neutralizing domain on the membrane form of the MT envelope appear to be cryptic or hidden from blocking antibodies. C1 NCI,CTR BIOL EVALUAT & RES,DIV HEMATOL PROD,BETHESDA,MD 20892. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. GENENTECH INC,DEPT IMMUNOL,S SAN FRANCISCO,CA 94080. NR 45 TC 219 Z9 221 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1994 VL 68 IS 9 BP 6006 EP 6013 PG 8 WC Virology SC Virology GA PB785 UT WOS:A1994PB78500073 PM 8057475 ER PT J AU RIBAS, JC FUJIMURA, T WICKNER, RB AF RIBAS, JC FUJIMURA, T WICKNER, RB TI A CRYPTIC RNA-BINDING DOMAIN IN THE POL REGION OF THE L-A DOUBLE-STRANDED-RNA VIRUS GAG-POL FUSION PROTEIN SO JOURNAL OF VIROLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; COAT PROTEIN; YEAST; EXPRESSION; ENCAPSIDATION; REPLICATION; POLYMERASE; MUTANT; SITES AB ``The Pol region of the Gag-Pol fusion protein of the L-A double-stranded (ds) RNA virus of Saccharomyces cerevisiae has (i) a domain essential for packaging viral positive strands, (ii) consensus amino acid sequence patterns typical of RNA-dependent RNA polymerases, and (iii) two single-stranded RNA binding domains. We describe here a third single-stranded RNA binding domain (Pol residues 374 to 432), which is unique in being cryptic. Its activity is revealed only after deletion of an inhibitory region C terminal to the binding domain itself. This cryptic RNA binding domain is necessary for propagation of M(1), satellite dsRNA, but it is not necessary for viral particle assembly or for packaging of viral positive-strand single-stranded RNA, The cryptic RNA binding domain includes a sequence pattern common among positive-strand single-stranded RNA and dsRNA viral RNA-dependent RNA polymerases, suggesting that it has a role in RNA polymerase activity. RP NIDDK, BIOCHEM PHARMACOL LAB, BLDG 8, ROOM 225, BETHESDA, MD 20892 USA. RI Fujimura, Tsutomu/K-5807-2014; Ribas, Juan/C-9864-2015 OI Fujimura, Tsutomu/0000-0002-9457-6769; Ribas, Juan/0000-0001-6430-0895 NR 27 TC 10 Z9 11 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD SEP PY 1994 VL 68 IS 9 BP 6014 EP 6020 PG 7 WC Virology SC Virology GA PB785 UT WOS:A1994PB78500074 PM 8057476 ER PT J AU WARD, P URCELAY, E KOTIN, R SAFER, B BERNS, KI AF WARD, P URCELAY, E KOTIN, R SAFER, B BERNS, KI TI ADENOASSOCIATED VIRUS-DNA REPLICATION IN-VITRO - ACTIVATION BY A MALTOSE-BINDING PROTEIN REP 68 FUSION PROTEIN SO JOURNAL OF VIROLOGY LA English DT Article ID ADENOASSOCIATED VIRUS; RECOMBINANT PLASMIDS; NUCLEOTIDE-SEQUENCE; INVITRO; SITE; INTEGRATION; RESCUE; REP; AAV; TERMINI AB The adeno-associated virus (AAV) nonstructural protein Rep 68 is required for viral DNA replication. An in vitro assay has been developed in which addition of Rep 68 to an extract from uninfected HeLa cells supports AAV DNA replication. In this paper, we report characterization of the replication process when a fusion of the maltose binding protein and Rep 68, expressed in Escherichia coli, was used in the assay. Replication was observed when the template was either linear double-stranded AAV DNA or a plasmid construct containing intact AAV DNA. When the recombinant plasmid construct was used as the template, there was replication of pBR322 DNA as well as the AAV DNA; however, linear pBR322 DNA was not replicated. When the plasmid construct was the template, replication appeared to initiate on the intact plasmid and led to separation of the AAV sequences from those of the vector, a process which has been termed rescue. There was no evidence that replication could initiate on the products of rescue. Rep 68 can make a site-specific nick 124 nucleotides from the 3' end of AAV DNA; the site of the nick has been called the terminal resolution site. Our data are most consistent with initiation occurring at the terminal resolution site and proceeding toward the 3' terminus. When the template was the plasmid construct, either elongation continued past the junction into pBR322 sequences or the newly synthesized sequence hairpinned, switched template strands, and replicated the AAV DNA. Replication was linear for 4 h, during which time 70% of the maximal synthesis took place. An additional finding was that the Rep fusion could resolve AAV dimer length duplex intermediates into monomer duplexes without DNA synthesis. C1 CORNELL UNIV, COLL MED, HEARST MICROBIOL RES CTR, DEPT MICROBIOL, NEW YORK, NY 10021 USA. NHLBI, MOLEC HEMATOL BRANCH, BETHESDA, MD 20892 USA. GENET THERAPY INC, GAITHERSBURG, MD 20878 USA. RI kotin, robert/B-8954-2008 FU NIGMS NIH HHS [GM 50032] NR 31 TC 42 Z9 42 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1994 VL 68 IS 9 BP 6029 EP 6037 PG 9 WC Virology SC Virology GA PB785 UT WOS:A1994PB78500076 PM 8057478 ER PT J AU BALDICK, CJ CASSETTI, MC HARRIS, N MOSS, B AF BALDICK, CJ CASSETTI, MC HARRIS, N MOSS, B TI ORDERED ASSEMBLY OF A FUNCTIONAL PREINITIATION TRANSCRIPTION COMPLEX, CONTAINING VACCINIA VIRUS EARLY TRANSCRIPTION FACTOR AND RNA-POLYMERASE, ON AN IMMOBILIZED TEMPLATE SO JOURNAL OF VIROLOGY LA English DT Note ID EARLY GENES; POLY(A) POLYMERASE; DEPENDENT TRANSCRIPTION; MESSENGER-RNA; SUBUNIT; VIRIONS; PROMOTER; IDENTIFICATION; PURIFICATION; SEQUENCE AB A functional preinitiation transcription complex was formed by incubating vaccinia virus early transcription factor VETF and RAP94(+) RNA polymerase with an early promoter template immobilized on paramagnetic particles. A preferred order of assembly, VETF followed by RNA polymerase, was demonstrated by stepwise addition experiments. ATP was unnecessary for preinitiation transcription complex formation, but divalent cations were required specifically for the association of RNA polymerase. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NR 45 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1994 VL 68 IS 9 BP 6052 EP 6056 PG 5 WC Virology SC Virology GA PB785 UT WOS:A1994PB78500079 PM 8057480 ER PT J AU REIN, A HARVIN, DP MIRRO, J ERNST, SM GORELICK, RJ AF REIN, A HARVIN, DP MIRRO, J ERNST, SM GORELICK, RJ TI EVIDENCE THAT A CENTRAL DOMAIN OF NUCLEOCAPSID PROTEIN IS REQUIRED FOR RNA PACKAGING IN MURINE LEUKEMIA-VIRUS SO JOURNAL OF VIROLOGY LA English DT Note ID CYS-HIS MOTIFS; VIRAL-RNA; DIMER FORMATION; ZINC FINGERS; ANNEALING ACTIVITIES; CIS ELEMENTS; READ-THROUGH; TYPE-1; SEQUENCE; RETROVIRUSES AB We have analyzed RNA packaging by a series of mutants altered in the nucleocapsid (NC) protein of Moloney murine leukemia virus (Mo-MuLV). We found that mutants lacking residues 8 through 11 or 44 through 60 of NC package Mo-MuLV RNA with virtually the same efficiency as wild-type Mo-MuLV. In contrast, point mutants altered at the conserved cysteines in the cysteine array (residues 26 and 29) and a mutant lacking residues 16 through 23 packaged Mo-MuLV RNA with approximately 1% of the efficiency of mild-type Mo-MuLV. The deficiency in packaged RNA was observed not only in Northern (RNA) analysis but also in an RNA-PCR assay, which would detect degraded as well as intact RNA. One of the cysteine array mutants was also shown to be defective with respect to encapsidation of hygromycin phosphotransferase mRNA containing a Mo-MuLV Packaging signal. We suggest that a central region of NC, consisting of the cysteine array and flanking basic residues, is required for RNA packaging in Mo-MuLV. C1 NCI, FREDERICK CANC RES & DEV CTR, PROGRAM RESOURCES INC DYNCORP, FREDERICK, MD 21702 USA. RP REIN, A (reprint author), NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, POB B, FREDERICK, MD 21702 USA. FU NCI NIH HHS [N01-CO-74102, N01-CO-74101] NR 41 TC 63 Z9 63 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1994 VL 68 IS 9 BP 6124 EP 6129 PG 6 WC Virology SC Virology GA PB785 UT WOS:A1994PB78500094 PM 8057495 ER PT J AU RAY, PE BRUGGEMAN, LA WEEKS, BS KOPP, JB BRYANT, JL OWENS, JW NOTKINS, AL KLOTMAN, PE AF RAY, PE BRUGGEMAN, LA WEEKS, BS KOPP, JB BRYANT, JL OWENS, JW NOTKINS, AL KLOTMAN, PE TI BFGF AND ITS LOW-AFFINITY RECEPTORS IN THE PATHOGENESIS OF HIV-ASSOCIATED NEPHROPATHY IN TRANSGENIC MICE SO KIDNEY INTERNATIONAL LA English DT Article ID FIBROBLAST GROWTH-FACTOR; HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE-DEFICIENCY SYNDROME; EPITHELIAL-CELLS INVITRO; ENDOTHELIAL-CELLS; BASEMENT-MEMBRANES; KAPOSIS-SARCOMA; GENE-EXPRESSION; MESANGIAL CELLS; HEPARAN-SULFATE AB HIV-associated nephropathy is characterized by extensive tubulointerstitial disease with epithelial cell injury, microcystic proliferation, and tubular regeneration with glomerulosclerosis. To explore the role of bFGF as a mediator of HIV-induced interstitial disease, we utilized an HIV transgenic mouse model that manifests clinical and histological features observed in patients. In transgenic mice, simultaneous renal epithelial cell proliferation and injury were detected in vivo. In areas of microcystic proliferation, immunoreactive bFGF colocalized with extracellular matrix. Kidneys from transgenic mice had increased bFGF low affinity binding sites, particularly in the renal interstitium. In vitro, transgenic renal tubular epithelial cells proliferated more rapidly and generated tubular structures spontaneously, in marked contrast to nontransgenic renal cells where these pathologic features could be mimicked by exogenous bFGF. These studies suggest that renal bFGF and its receptors play an important role in the pathogenesis of HIV-associated nephropathy. C1 NIH,NATL CTR RES RESOURCES,ORAL MED LAB,VIRAL PATHOGENESIS UNIT,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,BETHESDA,MD 20892. CHILDRENS HOSP,NATL MED CTR,CHILDRENS RES INST,WASHINGTON,DC 20010. HAMILTON COLL,DEPT BIOL,CLINTON,NY. RP RAY, PE (reprint author), NIDR,ANIM CARE UNIT,BLDG 30,ROOM 433,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Kopp, Jeffrey/0000-0001-9052-186X NR 51 TC 79 Z9 80 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 1994 VL 46 IS 3 BP 759 EP 772 DI 10.1038/ki.1994.331 PG 14 WC Urology & Nephrology SC Urology & Nephrology GA PC217 UT WOS:A1994PC21700021 PM 7996798 ER PT J AU BERENCSI, K URI, A VALYINAGY, T VALYINAGY, I MEIGNIER, B PERETZ, FV RANDO, RF PLOTKIN, SA GONCZOL, E AF BERENCSI, K URI, A VALYINAGY, T VALYINAGY, I MEIGNIER, B PERETZ, FV RANDO, RF PLOTKIN, SA GONCZOL, E TI EARLY REGION 3-REPLACEMENT ADENOVIRUS RECOMBINANTS ARE LESS PATHOGENIC IN COTTON RATS AND MICE THAN EARLY REGION 3-DELETED VIRUSES SO LABORATORY INVESTIGATION LA English DT Article DE ADENOVIRUS REPLICATION; VIRUS GENOME SIZE ID HERPES-SIMPLEX VIRUS; TRIGEMINAL GANGLIA; GENE-EXPRESSION; GLYCOPROTEIN-B; E3; PNEUMONIA; INFECTION; TYPE-5; DISEASE; VECTORS AB BACKGROUND: Adenovirus type-5 (Ad5) recombinant viruses with replacement of the 1.9 kb XbaI fragment in the early region 3 (E3) by foreign genes have been constructed with the ultimate goal of inducing immune responses to the product of the inserted gene against a variety of virus infections. The pathogenicity of these recombinants, however, has not been studied. EXPERIMENTAL DESIGN: Histopathologic changes induced in cotton rat and mouse lung by E3-replacement-Ad5 recombinant or wild-type Ad (Wt-Ad) or E3-deleted mutant (Ad5-Delta E3) viruses were compared. Expression of viral mRNA and replication of these viruses in cotton rat and mouse lungs, as well as in human tissue culture cells, were assayed. Expression of class I major histocompatibility complex antigens and the E3-14.7 kilodalton protein in virus-infected cells were also analyzed. RESULTS: An Ad5 recombinant, Ad-human cytomegalovirus glycoprotein B (Ad-HCMV.gB), in which the E3 region is replaced by the full-length gB gene of HCMV and with a genome size exceeding that of Wt-Ad, induced mild histopathologic responses in cotton rat and mouse lungs, comparable with those of Wt-Ad, but less severe than those of Ad5-Delta E3. Analysis indicated that neither class I major histocompatibility complex expression on the cell surface nor differential expression of the protective E3-14.7 kilodalton protein underlies the pathologic differences observed in cells infected with Ad5-Delta E3 or the Ad-HCMV.gB recombinant. In the mouse lung, another Ad-E3 replacement recombinant, Ad-herpes simplex glycoprotein B (HSV.gB), containing the complete HSV.gB gene and with a genome size larger than that of Wt-Ad, also induced a very mild inflammatory response. However, two recombinants with truncated forms of the HCMV.gB (Ad-HCMV.gB.155) or HSV.gB genes (Ad-HSV.gB.147) produced more severe histopathologic changes than the Wt-Ad or the recombinants with the full complement of HCMV.gB or HSV.gB genes. Ad5 and some of the recombinants replicated in mouse and cotton rat lung, and the extent of replication was inversely proportional to genome size, both in the lung and in human tissue culture cells. Infectious virus titers were, however, higher in cotton rat than in mouse lung. In situ hybridization analysis of cotton rat and mouse lung infected with Wt-Ad, Ad5-Delta E3, or Ad-HCMV.gB virus revealed expression of Ad early/late mRNA predominantly in bronchial epithelial cells. CONCLUSIONS: These data not only confirm that E3-deleted viruses induce more severe pathologic changes in cotton rat lungs than Wt-Ad viruses (Ginsberg et al., Proc Natl Acad Sci USA 1989;86:3823-7) but led to the observation that some E3 replacement recombinants also lacking the expression of the 19 and 14.7 kilodalton proteins are significantly less pathogenic in cotton rats and mice than an E3-deleted virus. Pathogenicity and replication of the recombinant viruses inversely correlate with the genomic size. C1 CHILDRENS HOSP PHILADELPHIA,DEPT PATHOL,PHILADELPHIA,PA 19104. INST PASTEUR MERIEUX,F-69280 MARCY LETOILE,FRANCE. NIDR,BETHESDA,MD 20892. WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104. FU NICHD NIH HHS [HD18957] NR 30 TC 13 Z9 13 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD SEP PY 1994 VL 71 IS 3 BP 350 EP 358 PG 9 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA PL094 UT WOS:A1994PL09400003 PM 7933985 ER PT J AU ROSENBERG, GA DENCOFF, JE MCGUIRE, PG LIOTTA, LA STETLERSTEVENSON, WG AF ROSENBERG, GA DENCOFF, JE MCGUIRE, PG LIOTTA, LA STETLERSTEVENSON, WG TI INJURY-INDUCED 92-KILODALTON GELATINASE AND UROKINASE EXPRESSION IN RAT-BRAIN SO LABORATORY INVESTIGATION LA English DT Article DE BACTERIAL COLLAGENASE; BLOOD-BRAIN BARRIER; BRAIN EDEMA; MATRIX METALLOPROTEINASES; PLASMINOGEN ACTIVATORS; TYPE IV COLLAGENASE; ZYMOGRAPHY ID CAPILLARY ENDOTHELIAL-CELLS; PLASMINOGEN-ACTIVATOR; IV COLLAGENASE; BASEMENT-MEMBRANE; HUMAN NEUTROPHIL; METALLOPROTEINASES; INHIBITORS; TISSUE; LEUKOCYTES; SECRETION AB BACKGROUND: Proteolytic disruption of the extracellular matrix is important in pathologic processes. We have shown that activated 72-kilodalton (kd) type IV collagenase injected intracerebrally attacks brain extracellular matrix and opens the blood-brain barrier. Therefore, we tested the hypothesis that endogenous production of matrix-degrading proteases may be a factor in secondary brain injury. EXPERIMENTAL DESIGN: Adult rats had a hemorrhagic injury produced by injection of 0.4 units of bacterial collagenase into the caudate/putamen. Endogenous production of matrix metal-loproteinases and plasminogen activators (PA) was measured by substrate-gel sodium dodecyl sulfate-polyacrylamide gel electrophoresis (zymography) at 1, 4, 8, 16, 24, and 48 hours, and 7 and 14 days after the injury. RESULTS: Gelatin-containing zymograms had bands of the expected molecular weights from the injected bacterial collagenase at 1 hour. By 8 hours a new 92-kd gelatinase was seen in zymograms. EDTA eliminated the 92-kd band, indicating that it was a metalloproteinase. The 92-kd type IV collagenase/gelatinase was maximally increased by 24 hours (p < 0.0001). Plasminogen-casein zymography showed 40- and 60-kd bands from PA. The 40-kd PA reached a maximum at 24 hours (p < 0.05) and remained elevated for 7 days. Amiloride completely eliminated the 40-kd band and reduced the 60-kd band, suggesting that they were a urokinase-type PA. CONCLUSIONS: Hemorrhagic injury induces both 92-kd type IV collagenase/gelatinase and 40-kd urokinase-plasminogen activator expression in brain. We propose that metalloproteinases and serine proteases take part in a proteolytic cascade that breaks down extracellular matrix, opening the blood-brain barrier with secondary brain edema and cell death. C1 UNIV NEW MEXICO,SCH MED,DEPT PHYSIOL,ALBUQUERQUE,NM 87131. UNIV NEW MEXICO,SCH MED,DEPT ANAT,ALBUQUERQUE,NM 87131. VET AFFAIRS MED CTR,NEUROL SERV,ALBUQUERQUE,NM. NCI,PATHOL LAB,BETHESDA,MD. RP ROSENBERG, GA (reprint author), UNIV NEW MEXICO,SCH MED,DEPT NEUROL,ALBUQUERQUE,NM 87131, USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 FU NHLBI NIH HHS [HL-46865]; NINDS NIH HHS [R01-NS21169] NR 37 TC 110 Z9 114 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD SEP PY 1994 VL 71 IS 3 BP 417 EP 422 PG 6 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA PL094 UT WOS:A1994PL09400012 PM 7933992 ER PT J AU DUYN, JH VANGELDEREN, P LIU, GY MOONEN, CTW AF DUYN, JH VANGELDEREN, P LIU, GY MOONEN, CTW TI FAST VOLUME SCANNING WITH FREQUENCY-SHIFTED BURST MRI SO MAGNETIC RESONANCE IN MEDICINE LA English DT Note DE MRI; BURST; FAST MRI; BRAIN ID NMR; CONTRAST; SEQUENCE; BRAIN AB We introduce a modified BURST imaging technique with reduced saturation effects and improved signal-to-noise ratio. The method applies a frequency shift to the RF excitation pulse on successive repetitions. It allows collection of 3D datasets of human brain within a few seconds, on a standard clinical scanner at 1.5 Tesla. RP DUYN, JH (reprint author), NIH,OIR,DIAGNOST RADIOL RES LAB,BLDG 10,ROOM B1N256,BETHESDA,MD 20892, USA. RI Duyn, Jozef/F-2483-2010; Moonen, Chrit/K-4434-2016 OI Moonen, Chrit/0000-0001-5593-3121 NR 11 TC 20 Z9 20 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 SEP PY 1994 VL 32 IS 3 BP 429 EP 432 DI 10.1002/mrm.1910320321 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PE259 UT WOS:A1994PE25900020 PM 7984078 ER PT J AU ZHA, H REMMERS, EF DU, Y GOLDMUNTZ, EA MATHERN, P ZHANG, H CASH, JM CROFFORD, LJ WILDER, RL AF ZHA, H REMMERS, EF DU, Y GOLDMUNTZ, EA MATHERN, P ZHANG, H CASH, JM CROFFORD, LJ WILDER, RL TI A SINGLE LINKAGE GROUP COMPRISING 11 POLYMORPHIC DNA MARKERS ON RAT CHROMOSOME-3 SO MAMMALIAN GENOME LA English DT Article ID PRIMERS; MAP AB Eleven polymorphic DNA markers were mapped to rat Chromosome (Chr) 3 by linkage analysis of F-2 progeny of F344/N and LEW/N rat strains. The markers, including seven genes and four anonymous loci, formed a single linkage group covering approximately 112 cM with the following order: Ptgs1 (prostaglandin G/H synthase I)-D3Arb178-Scn2a (sodium channel, type II, alpha-polypeptide)-D3Arb1-Cat (catalase)-Bdnf (brain-derived neurotrophic factor)-D3Arb219-D3Arb2-Sus2 (seminal vesicle secretion II protein)-Sdc4 (ryudocan/syndecan4)-Stnl (statin-like protein). Eight of these markers were analyzed for polymorphisms in 14 additional inbred rat strains. Three to five alleles were detected for each marker, suggesting that they are highly polymorphic and useful for genetic mapping studies with inbred rat strains. Chromosomal syntenic conservation among rats, mice and humans is also discussed. C1 NIAMSD,ARTHRITIS & RHEUMAT BRANCH,BETHESDA,MD 20892. RI Crofford, Leslie/J-8010-2013 NR 12 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD SEP PY 1994 VL 5 IS 9 BP 538 EP 541 DI 10.1007/BF00354926 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA PE646 UT WOS:A1994PE64600003 PM 8000136 ER PT J AU TOMER, KB MOSELEY, MA DETERDING, LJ PARKER, CE AF TOMER, KB MOSELEY, MA DETERDING, LJ PARKER, CE TI CAPILLARY LIQUID-CHROMATOGRAPHY MASS-SPECTROMETRY SO MASS SPECTROMETRY REVIEWS LA English DT Review ID FAST-ATOM-BOMBARDMENT; OPEN-TUBULAR COLUMNS; ELECTROSPRAY-IONIZATION; NANOSCALE SEPARATIONS; PROTEIN-ANALYSIS; INNER DIAMETERS; MU-M; PERFORMANCE; PEPTIDES; INTERFACE RP TOMER, KB (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Tomer, Kenneth/E-8018-2013 NR 120 TC 55 Z9 59 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0277-7037 J9 MASS SPECTROM REV JI Mass Spectrom. Rev. PD SEP-NOV PY 1994 VL 13 IS 5-6 BP 431 EP 457 DI 10.1002/mas.1280130504 PG 27 WC Spectroscopy SC Spectroscopy GA RR701 UT WOS:A1994RR70100003 ER PT J AU ZOLKIEWSKA, A OKAZAKI, IJ MOSS, J AF ZOLKIEWSKA, A OKAZAKI, IJ MOSS, J TI VERTEBRATE MONO-ADP-RIBOSYLTRANSFERASES SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE ADP-RIBOSYLARGININE HYDROLASE; GLYCOSYLPHOSPHATIDYLINOSITOL ANCHOR; SKELETAL MUSCLE; CHOLERA TOXIN; ADP-RIBOSYLTRANSFERASES ID GLUCOSE-REGULATED PROTEIN; RABBIT SKELETAL-MUSCLE; ELONGATION FACTOR-II; TURKEY ERYTHROCYTES; SARCOPLASMIC-RETICULUM; GLYCOSYL-PHOSPHATIDYLINOSITOL; SUPPRESSES PHOSPHORYLATION; POLYMORPHONUCLEAR CELLS; CA-2+-DEPENDENT ATPASE; ADENYLATE-CYCLASE AB Mono-ADP-ribosylation appears to be a reversible modification of proteins, which occurs in many eukaryotic and prokaryotic organisms. Multiple forms of arginine-specific ADP-ribosyltransferases have been purified and characterized from avian erythrocytes, chicken polymorphonuclear leukocytes and mammalian skeletal muscle. The avian transferases have similar molecular weights of similar to 28 kDa, but differ in physical, regulatory and kinetic properties and subcellular localization. Recently, a 38-kDa rabbit skeletal muscle ADP-ribosyltransferase was purified and cloned. The deduced amino acid sequence contained hydrophobic amino and carboxy termini, consistent with known signal sequences of glycosylphosphatidylinositol (GPI)-anchored proteins. This arginine-specific transferase was present on the surface of mouse myotubes and of NMU cells transfected with the cDNA and was released with phosphatidylinositol-specific phospholipase C. Arginine-specific ADP-ribosyltransferases thus appear to exhibit considerable diversity in their structure, cellular localization, regulation and physiological role. RP ZOLKIEWSKA, A (reprint author), NHLBI,CELLULAR METAB LAB,BLDG 10,ROOM 5N-307,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 60 TC 29 Z9 29 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD SEP PY 1994 VL 138 IS 1-2 BP 107 EP 112 DI 10.1007/BF00928450 PG 6 WC Cell Biology SC Cell Biology GA PU052 UT WOS:A1994PU05200014 PM 7898451 ER PT J AU TAKADA, T OKAZAKI, IJ MOSS, J AF TAKADA, T OKAZAKI, IJ MOSS, J TI ADP-RIBOSYLARGININE HYDROLASES SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE ADP-RIBOSYLARGININE HYDROLASE; MONO-ADP-RIBOSYLATION; ADP-RIBOSYLTRANSFERASE; CHOLERA TOXIN ID TURKEY ERYTHROCYTES; SUBSTRATE-SPECIFICITY; ADENYLATE-CYCLASE; SKELETAL-MUSCLE; NAD; RIBOSYLATION; RIBOSYLTRANSFERASE; ARGININE; PROTEIN; IDENTIFICATION AB ADP-ribosylation is a reversible post-translational modification of proteins involving the addition of the ADP-ribose moiety of NAD to an acceptor protein or amino acid. NAD:arginine ADP-ribosyltransferase, purified from numerous animal tissues, catalyzes the transfer of ADP-ribose to an arginine residue in proteins. The reverse reaction, catalyzed by ADP-ribosylarginine hydrolase, removes ADP-ribose, regenerating free arginine. An ADP-ribosylarginine hydrolase, purified extensively from turkey erythrocytes, was a 39-kDa monomeric protein under denaturing and non-denaturing conditions, and was activated by Mg2+ and dithiothreitol. The ADP-ribose moiety was critical for substrate recognition; the enzyme hydrolyzed ADP-ribosylarginine and (2-phospho-ADP-ribosyl)arginine but not phosphoribosylarginine or ribosylarginine. The hydrolase cDNA was cloned from rat and subsequently from mouse and human brain. The rat hydrolase gene contained a 1086-base pair open reading frame, with deduced amino acid sequences identical to those obtained by amino terminal sequencing of the protein or of HPLC-purified tryptic peptides. Deduced amino acid sequences from the mouse and human hydrolase cDNAs were 94% and 83% identical, respectively to the rat. Anti-rat brain hydrolase polyclonal antibodies reacted with turkey erythrocyte, mouse and bovine brain hydrolase. The rat hydrolase, expressed in E. coli, demonstrated enhanced activity in the presence of Mg2+ and thiol, whereas the recombinant human hydrolase was stimulated by Mg2+ but was thiol-independent. In the rat and mouse enzymes, there are five cysteines in identical positions; four of the cysteines are conserved in the human hydrolase. Replacement of cysteine 108 in the rat hydrolase (not present in the human enzyme) resulted in a thiol-independent hydrolase without altering specific activity. Rabbit anti-rat brain hydrolase antibodies reacted on immunoblot with the wild-type rat hydrolase and only weakly with the mutant hydrolase. There was no immunoreactivity with either the wild-type or mutant human enzyme. Cysteine 108 in the rat and mouse hydrolase may be responsible in part for thiol-dependence as well as antibody recognition. Based on these studies, the mammalian and avian ADP-ribosylarginine hydrolases exhibit considerable conservation in structure and function. RP TAKADA, T (reprint author), NHLBI,CELLULAR METAB LAB,9000 ROCKVILE PIKE,BLDG 10,ROOM 5N307,BETHESDA,MD 20892, USA. NR 27 TC 16 Z9 16 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD SEP PY 1994 VL 138 IS 1-2 BP 119 EP 122 DI 10.1007/BF00928452 PG 4 WC Cell Biology SC Cell Biology GA PU052 UT WOS:A1994PU05200016 PM 7898453 ER PT J AU WELSH, CF MOSS, J VAUGHAN, M AF WELSH, CF MOSS, J VAUGHAN, M TI ADP-RIBOSYLATION FACTORS - A FAMILY OF SIMILAR-TO-20-KDA GUANINE-NUCLEOTIDE-BINDING PROTEINS THAT ACTIVATE CHOLERA-TOXIN SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE CHOLERA TOXIN; ADENYLYL CYCLASE; ADP-RIBOSYLATION FACTORS; GUANINE NUCLEOTIDE-BINDING (G) PROTEINS; VESICULAR TRAFFICKING ID NICOTINAMIDE ADENINE-DINUCLEOTIDE; ADENYLATE-CYCLASE; BREFELDIN-A; RIBOSYLTRANSFERASE ACTIVITY; REGULATORY COMPONENT; FACTOR ARF; FACTOR-III; ENZYMIC ACTIVITY; GOLGI MEMBRANES; MESSENGER-RNA AB ADP-ribosylation factors (ARFs) comprise a family of similar to 20 kDa guanine nucleotide-binding proteins that were discovered as one of several cofactors required in cholera toxin-catalyzed ADP-ribosylation of G(s alpha), the guanine nucleotide-binding protein responsible for stimulation of adenylyl cyclase, and was subsequently found to enhance all cholera toxin-catalyzed reactions and to directly interact with, and activate the toxin. ARF is dependent on GTP or its analogues for activity, binds GTP with high affinity in the presence of dimyristoylphosphatidylcholine/cholate and contains consensus sequences for GTP-binding and hydrolysis. Six mammalian family members have been identified which have been classified into three groups (Class I, II, and III) based on size, deduced amino acid sequence identity, phylogenetic analysis and gene structure. ARFs are ubiquitous among eukaryotes, with a deduced amino acid sequence that is highly conserved across diverse species. They have recently been shown to associate with phospholipid and Golgi membranes in a GTP-dependent manner and are involved in regulating vesicular transport. RP WELSH, CF (reprint author), NHLBI,CELLULAR METAB LAB,ROOM 5N-307,BLDG 10,BETHESDA,MD 20892, USA. NR 83 TC 38 Z9 40 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD SEP PY 1994 VL 138 IS 1-2 BP 157 EP 166 DI 10.1007/BF00928458 PG 10 WC Cell Biology SC Cell Biology GA PU052 UT WOS:A1994PU05200022 PM 7898460 ER PT J AU OKAZAKI, IJ MOSS, J AF OKAZAKI, IJ MOSS, J TI COMMON STRUCTURE OF THE CATALYTIC SITES OF MAMMALIAN AND BACTERIAL TOXIN ADP-RIBOSYLTRANSFERASES SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE ADP-RIBOSYLTRANSFERASE; DIPHTHERIA TOXIN; CHOLERA TOXIN; PERTUSSIS TOXIN; C3 EXOENZYME ID AMINO-ACID-SEQUENCE; AERUGINOSA EXOTOXIN-A; ESCHERICHIA-COLI ENTEROTOXIN; CELL ALLOANTIGEN RT-6.2; RABBIT SKELETAL-MUSCLE; NAD-BINDING-SITE; PSEUDOMONAS-AERUGINOSA; DIPHTHERIA-TOXIN; PERTUSSIS TOXIN; CHOLERA-TOXIN AB The amino acid sequences of several bacterial toxin ADP-ribosyltransferases, rabbit skeletal muscle transferases, and RT6.2, a rat T-cell NAD glycohydrolase, contain three separate regions of similarity, which can be aligned. Region I contains a critical histidine or arginine residue, region II, a group of closely spaced aromatic amino acids, and region III, an active-site glutamate which is at time sseen as part of an acidic amino acid-rich sequence. In some of the bacterial ADP-ribosyltransferases, the nicotinamide moiety of NAD has been photo-crosslinked to this glutamate, consistent with its position in the active site. The similarities within these three regions, despite an absence of overall sequence similarity among the several transferases, are consistent with a common structure involved in NAD binding and ADP-ribose transfer. RP NHLBI, CELLULAR METAB LAB, 9000 ROCKVILLE PIKE, BLDG 10, ROOM 5N307, BETHESDA, MD 20892 USA. NR 46 TC 24 Z9 24 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 EI 1573-4919 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD SEP PY 1994 VL 138 IS 1-2 BP 177 EP 181 DI 10.1007/BF00928460 PG 5 WC Cell Biology SC Cell Biology GA PU052 UT WOS:A1994PU05200024 PM 7898462 ER PT J AU MCDONALD, LJ MOSS, J AF MCDONALD, LJ MOSS, J TI NITRIC-OXIDE AND NAD-DEPENDENT PROTEIN MODIFICATION SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE NITRIC OXIDE; NAD; ADP-RIBOSYLATION; CYSTEINE ID ENDOGENOUS ADP-RIBOSYLATION; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; POLY(ADP-RIBOSE) POLYMERASE; S-NITROSYLATION; RELAXING FACTOR; SERUM-ALBUMIN; L-ARGININE; CELLS; RIBOSYLTRANSFERASE; INHIBITION AB Nitric oxide (NO) has been suggested to act as a regulator of endogenous intracellular ADP-ribosylation, based on radiolabelling of proteins in tissue homogenates incubated with [P-32]NAD and NO. After the NO-stimulated modification was replicated in a defined system containing only the purified acceptor protein, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), the hypothesis of NO-stimulation of an endogenous ADP-ribosyltransferase became moot. The NO-stimulated, NAD-dependent modification of GAPDH was recently characterized as covalent binding of the whole NAD molecule to the enzyme, not ADP-ribosylation. With this result, along with the knowledge that GAPDH is stoichiometrically S-nitrosylated, the role of NO in protein modification with NAD may be viewed as the conferring of an unexpected chemical reactivity upon GAPDH, possibly due to nitrosylation of a cysteine in the enzyme active site. RP MCDONALD, LJ (reprint author), NHLBI,CELLULAR METAB LAB,BLDG 10-5N-307,BETHESDA,MD 20892, USA. NR 44 TC 23 Z9 24 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD SEP PY 1994 VL 138 IS 1-2 BP 201 EP 206 DI 10.1007/BF00928462 PG 6 WC Cell Biology SC Cell Biology GA PU052 UT WOS:A1994PU05200026 PM 7898464 ER PT J AU MCDONALD, LJ MOSS, J AF MCDONALD, LJ MOSS, J TI ENZYMATIC AND NONENZYMATIC ADP-RIBOSYLATION OF CYSTEINE SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE ADP-RIBOSYLATION; CYSTEINE; PERTUSSIS TOXIN; MERCURY ID GTP-BINDING PROTEINS; AMINO-ACID SEQUENCE; NITRIC-OXIDE; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; PERTUSSIS TOXIN; HUMAN-ERYTHROCYTES; ALDEHYDE DEHYDROGENASE; LIVER-MITOCHONDRIA; BACTERIAL TOXINS; SKELETAL-MUSCLE AB Mono-ADP-ribosylation is a protein modification that occurs at a number of different amino acids, dictated by the specificity of the individual ADP-ribosyltransferases. A specific cysteine in several guanine nucleotide-binding regulatory proteins is ADP-ribosylated by the bacterial protein pertussis toxin. Recent purification of an ADP-ribosylcysteine hydrolase and NAD:cysteine ADP-ribosyltransferase, and detection of ADP-ribose-cysteine linkages in tissue samples has raised hope that an endogenous regulatory cysteine-specific ADP-ribosylation pathway exists. A current goal is the identification of such a pathway for ADP-ribosylation of cysteine within animal cells. Interpretation of the data in this field has been complicated by recent reports that revealed several unforeseen chemical reactions of NAD and its metabolites with free cysteine and cysteine in proteins. This mini-review covers the latest understanding of the ADP-ribosylation reactions associated with cysteine, and provides a set of criteria for future research to establish positively the existence of an endogenous cysteine-specific mono-ADP-ribosyltransferase. RP MCDONALD, LJ (reprint author), NHLBI,CELLULAR METAB LAB,BLDG 10-5N-307,BETHESDA,MD 20892, USA. NR 54 TC 35 Z9 35 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD SEP PY 1994 VL 138 IS 1-2 BP 221 EP 226 DI 10.1007/BF00928465 PG 6 WC Cell Biology SC Cell Biology GA PU052 UT WOS:A1994PU05200029 PM 7898467 ER PT J AU GRAEBER, TG PETERSON, JF TSAI, M MONICA, K FORNACE, AJ GIACCIA, AJ AF GRAEBER, TG PETERSON, JF TSAI, M MONICA, K FORNACE, AJ GIACCIA, AJ TI HYPOXIA INDUCES ACCUMULATION OF P53 PROTEIN, BUT ACTIVATION OF A G(1)-PHASE CHECKPOINT BY LOW-OXYGEN CONDITIONS IS INDEPENDENT OF P53 STATUS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID WILD-TYPE P53; CELLULAR TUMOR-ANTIGEN; DNA-DAMAGING AGENTS; GLUCOSE-REGULATED PROTEINS; SHOCK TRANSCRIPTION FACTOR; HAMSTER OVARY CELLS; HEAT-SHOCK; MAMMALIAN-CELLS; GENE AMPLIFICATION; CYCLE PROGRESSION AB It has been convincingly demonstrated that genotoxic stresses cause the accumulation of the tumor suppressor gene p53. One important consequence of increased p53 protein levels in response to DNA damage is the activation of a G(1)-phase cell cycle checkpoint. It has also been shown that G(1)-phase cell cycle checkpoints are activated in response to other stresses, such as lack of oxygen. Were we show that hypoxia and heat, agents that induce cellular stress primarily by inhibiting oxygen-dependent metabolism and denaturing proteins, respectively, also cause an increase in p53 protein levels. The p53 protein induced by heat is localized in the cytoplasm and forms a complex with the heat shock protein hsc70. The increase in nuclear p53 protein levels and DNA-binding activity and the induction of reporter gene constructs containing p53 binding sites following hypoxia occur in cells that are wild type for p53 but not in cells that possess mutant p53. However, unlike ionizing radiation, the accumulation of cells in G, phase by hypoxia is not strictly dependent on wild-type p53 function. In addition, cells expressing the human papillomavirus E6 gene, which show increased degradation of p53 by ubiquitination and fail to accumulate p53 in response to DNA-damaging agents, do increase their p53 levels following heat and hypoxia. These results suggest that hypoxia is an example of a ''nongenotoxic'' stress which induces p53 activity by a different pathway than DNA-damaging agents. C1 STANFORD UNIV,SCH MED,DEPT RADIAT ONCOL,STANFORD,CA 94305. NCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RI Fornace, Albert/A-7407-2008; OI Fornace, Albert/0000-0001-9695-085X; Graeber, Thomas/0000-0001-8574-9181 FU NCI NIH HHS [NCI CA 58838-1] NR 85 TC 514 Z9 521 U1 0 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 1994 VL 14 IS 9 BP 6264 EP 6277 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PC750 UT WOS:A1994PC75000068 PM 8065358 ER PT J AU KAMBOURIS, M SANGAMESWARAN, L TRIARHOU, LC KOZAK, CA DLOUHY, SR GHETTI, B HODES, ME AF KAMBOURIS, M SANGAMESWARAN, L TRIARHOU, LC KOZAK, CA DLOUHY, SR GHETTI, B HODES, ME TI MOLECULAR CHARACTERIZATION OF A NOVEL CDNA FROM MURINE CEREBELLUM, DEVELOPMENTAL EXPRESSION, AND DISTRIBUTION IN BRAIN SO MOLECULAR BRAIN RESEARCH LA English DT Article DE CDNA; CEREBELLUM; GRANULE CELL; HUMAN; HIPPOCAMPAL FORMATION; IN SITU HYBRIDIZATION; MOUSE; OLFACTORY BULB; SUBSTANTIA NIGRA ID POSTNATAL-DEVELOPMENT; MUTANT MICE; CORTEX; GENE; LAYER; RAT; MATURATION; RECEPTOR; WEAVER; CELLS AB Several novel cDNA clones were previously identified by immunoscreening a cerebellar cDNA expression library derived from heterozygous weaver (w upsilon / +) mice at postnatal day one (P1) with an antigranule cell antiserum. One cDNA, GCAP-8 (granule cell antiserum-positive clone 8) has been further characterized. The 1.1 kb insert is a partial cDNA containing a segment near the 3' end of the full-length cDNA. The 5' end of the GCAP-8 cDNA contains a 259 nucleotide open reading frame (ORF) coding for the last 85 amino acids of the carboxy terminus of the encoded protein. The encoded polypeptide contains two highly hydrophobic segments interrupted by a basic stretch. The carboxy terminus of this protein is cysteine-rich, with 10 cysteine residues among the 85 amino acids. The GCAP-8 cDNA probably represents a single-copy gene. The GCAP-8 gene, designated Gcap1, was mapped to the distal region of mouse chromosome 5 by the analyses of two multilocus crosses. The distribution of the GCAP-8 mRNA in mouse brain was studied by in situ hybridization histochemistry. In the adult mouse brain, strong hybridization was detected in cerebellum, hippocampus, substantia nigra (SN), and cerebral cortex. In mouse cerebellum, hybridization was detected in granule cells, Purkinje cells, and in cells of the deep cerebellar nuclei (DCN). In human cerebellum, hybridization was detected in the granule cell layer. In the mouse, GCAP-8 is expressed at least as early as embryonic day 14 (E14) in the central nervous system (CNS). C1 INDIANA UNIV,SCH MED,DEPT MED & MOLEC GENET,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,DEPT PATHOL & LAB MED,CELLULAR & MOLEC NEUROPATHOL LAB,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,PROGRAM MED NEUROBIOL,INDIANAPOLIS,IN 46202. NIH,BETHESDA,MD 20892. NR 20 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD SEP PY 1994 VL 25 IS 3-4 BP 192 EP 199 DI 10.1016/0169-328X(94)90153-8 PG 8 WC Neurosciences SC Neurosciences & Neurology GA PD787 UT WOS:A1994PD78700002 ER PT J AU RISINGER, JI TERRY, LA BOYD, J AF RISINGER, JI TERRY, LA BOYD, J TI USE OF REPRESENTATIONAL DIFFERENCE ANALYSIS FOR THE IDENTIFICATION OF MDM2 ONCOGENE AMPLIFICATION IN DIETHYLSTILBESTROL-INDUCED MURINE UTERINE ADENOCARCINOMAS SO MOLECULAR CARCINOGENESIS LA English DT Note DE ENDOMETRIAL CANCER; MDM2; CARCINOGENESIS; ESTROGEN; HORMONE ID CLEAR CELL ADENOCARCINOMA; GENE; PROTEIN; VAGINA; CARCINOGENESIS; EXPRESSION; ESTROGENS; INDUCTION; EXPOSURE; SARCOMAS AB Exposure in utero to the synthetic estrogen diethylstilbestrol (DES) is associated with the subsequent development of reproductive-tract malignancies in female offspring. To search for the genetic targets of DES, representational difference analysis was used to compare genomic DNA from DES-associated mouse uterine adenocarcinoma cells with genomic DNA from normal CD-1 mouse tissue. Several difference clones were obtained, all of which recognized rearranged and amplified sequences in tumor compared with normal DNA. One of these difference fragments mapped to a region of mouse chromosome 10 that includes the mdm2 oncogene. Amplification and overexpression of mdm2 was found in all three early-passage cell lines established from independent DES-associated cancers. These findings demonstrate the potential power of representational difference analysis in cancer research and suggest a genetic mechanism for DES-induced carcinogenesis. (C) 1994 Wiley-Liss, Inc.(*) C1 NIEHS,MOLEC CARCINOGENESIS LAB,GYNECOL PATHOBIOL SECT,RES TRIANGLE PK,NC 27709. NR 41 TC 12 Z9 12 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD SEP PY 1994 VL 11 IS 1 BP 13 EP 18 DI 10.1002/mc.2940110104 PG 6 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA PJ589 UT WOS:A1994PJ58900003 PM 7916985 ER PT J AU FORRESTER, K KISPERT, J SANCHEZ, JH GERWIN, BI TLSTY, TD HARRIS, CC AF FORRESTER, K KISPERT, J SANCHEZ, JH GERWIN, BI TLSTY, TD HARRIS, CC TI CLONAL VARIATION OF TUMORIGENIC POTENTIAL IN V-HA-VAS-TRANSFORMED HUMAN BRONCHIAL EPITHELIAL-CELLS - RELATIONSHIP TO RAS ONCOGENE EXPRESSION AND CAD GENE AMPLIFICATION SO MOLECULAR CARCINOGENESIS LA English DT Article DE RAS; TUMOR PROGRESSION; GENE AMPLIFICATION ID MURINE SARCOMA-VIRUS; METASTATIC ABILITY; TUMOR PROGRESSION; NEOPLASTIC TRANSFORMATION; HARVEY-RAS; 3T3 CELLS; K-RAS; CANCER; TRANSFECTION; INSTABILITY AB Infection of an SV40 large-T antigen-''immortalized'' human bronchial epithelial cell line with a Zip-v-Ha-ras retroviral vector resulted in a mass culture that was tumorigenic in athymic nude mice. A tumor cell line derived from passage of the mass culture in vivo, however, exhibited increased tumorigenicity and v-Ha-ras expression. To examine and compare the molecular events involving the ras oncogene during cell transformation in vitro and subsequent tumor formation in vivo, clonal cell populations were isolated from the v-Ha-ras-transformed mass culture. While the clonal cell lines exhibited diverse tumorigenic profiles, these differences did not correlate with v-Ha-ras expression. However, the expression of the activated ras gene, while not necessary for growth in vitro, did appear to be associated with a selective growth advantage in vivo. In addition, the modulation of gene amplification ability in these cells was not associated with the induction of tumorigenicity or v-Ha-ras expression. (C) 1994 Wiley-Liss, Inc.(*) C1 NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. UNIV N CAROLINA,LINEBERGER CANC RES CTR,DEPT PATHOL,CHAPEL HILL,NC 27599. FU NCI NIH HHS [CA51912] NR 38 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 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD SEP PY 1994 VL 11 IS 1 BP 34 EP 41 DI 10.1002/mc.2940110107 PG 8 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA PJ589 UT WOS:A1994PJ58900006 PM 7916988 ER PT J AU MAX, EE JAHAN, N YI, HF MCBRIDE, WO AF MAX, EE JAHAN, N YI, HF MCBRIDE, WO TI A PROCESSED J CHAIN PSEUDOGENE ON HUMAN-CHROMOSOME-8 THAT IS SHARED BY SEVERAL PRIMATE SPECIES SO MOLECULAR IMMUNOLOGY LA English DT Article DE EVOLUTION; IMMUNOGLOBULIN; GENE MAPPING; GENETIC LINKAGE ANALYSIS; DNA POLYMORPHISM; CHROMOSOMAL LOCALIZATION; RFLP ID IMMUNOGLOBULIN J-CHAIN; GENES; DNA; POLYMORPHISMS; LOCALIZATION; SEQUENCES; FAMILY; CELLS; SITE AB Human DNA contains two sequences that hybridize to a human J chain gene probe: the J chain gene itself and a second previously uncharacterized sequence. By cloning and sequence analysis we now show this related sequence to be a processed pseudogene, which we have localized using somatic hybrids to chromosome 8 (distinct from the functional gene on chromosome 4) and mapped by linkage analysis to 8q13-q21. The pseudogene provides evidence of an additional DNA insertion event as it contains an AluI element embedded in sequence corresponding to the 3' untranslated region of the gene. The extent of sequence divergence between the pseudogene and the functional J chain gene suggests that the pseudogene was created roughly 40-50 million years ago; consistent with this estimate, Southern blots suggest that the pseudogene is shared by great apes as well as Old World monkeys. C1 NCI,DIV CANC TREATMENT,BIOL CHEM LAB,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. RP MAX, EE (reprint author), US FDA,CTR BIOL EVALUAT & RES,HFM-541,BETHESDA,MD 20892, USA. NR 26 TC 4 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD SEP PY 1994 VL 31 IS 13 BP 1029 EP 1036 DI 10.1016/0161-5890(94)90097-3 PG 8 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA PH391 UT WOS:A1994PH39100008 PM 7916122 ER PT J AU KLIMPEL, KR ARORA, N LEPPLA, SH AF KLIMPEL, KR ARORA, N LEPPLA, SH TI ANTHRAX TOXIN LETHAL FACTOR CONTAINS A ZINC METALLOPROTEASE CONSENSUS SEQUENCE WHICH IS REQUIRED FOR LETHAL TOXIN ACTIVITY SO MOLECULAR MICROBIOLOGY LA English DT Article ID COMPLETE NUCLEOTIDE-SEQUENCE; BACILLUS-ANTHRACIS; PROTECTIVE ANTIGEN; TETANUS-TOXIN; PSEUDOMONAS-AERUGINOSA; NEUTRAL PROTEASE; NEUROTRANSMITTER RELEASE; MOLECULAR-CLONING; ADENYLATE-CYCLASE; EUKARYOTIC CELLS AB Comparison of the anthrax toxin lethal factor (LF) amino acid sequence with sequences in the Swiss protein database revealed short regions of similarity with the consensus zinc-binding site, HEXXH, that is characteristic of metalloproteases. Several protease inhibitors, including bestatin and captopril, prevented intoxication of macrophages by lethal toxin. LF was fully inactivated by site-directed mutagenesis that substituted Ala for either of the residues (H-686 and H-690) implicated in zinc binding. Similarly, LF was inactivated by substitution of Cys for E-687, which is thought to be an essential part of the catalytic site. In contrast, replacement of E-720 and E-721 with Ala had no effect on LF activity. LF bound Zn-65 both in solution and on protein blots. The Zn-65 binding was reduced for several of the LF mutants. These data suggest that anthrax toxin LF is a zinc metallopeptidase, the catalytic function of which is responsible for the lethal activity observed in cultured cells and in animals. C1 NIDR, MICROBIAL ECOL LAB, BETHESDA, MD 20892 USA. NR 57 TC 224 Z9 230 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X EI 1365-2958 J9 MOL MICROBIOL JI Mol. Microbiol. PD SEP PY 1994 VL 13 IS 6 BP 1093 EP 1100 DI 10.1111/j.1365-2958.1994.tb00500.x PG 8 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA PH482 UT WOS:A1994PH48200015 PM 7854123 ER PT J AU BENYA, RV AKESON, M MROZINSKI, J JENSEN, RT BATTEY, JF AF BENYA, RV AKESON, M MROZINSKI, J JENSEN, RT BATTEY, JF TI INTERNALIZATION OF THE GASTRIN-RELEASING PEPTIDE RECEPTOR IS MEDIATED BY BOTH PHOSPHOLIPASE C-DEPENDENT AND C-INDEPENDENT PROCESSES SO MOLECULAR PHARMACOLOGY LA English DT Article ID BETA-ADRENERGIC-RECEPTOR; BOMBESIN-LIKE PEPTIDES; GROWTH-FACTOR RECEPTOR; LIGAND-INDUCED INTERNALIZATION; 3RD CYTOPLASMIC LOOP; GUINEA-PIG PANCREAS; SWISS 3T3 CELLS; BETA-2-ADRENERGIC RECEPTOR; TRANSFERRIN RECEPTOR; EGF RECEPTOR AB Consequent to agonist exposure, many G protein-coupled receptors undergo sequestration or internalization. Results with receptors linked to adenylate cyclase, such as the beta(2)-adrenergic receptor, or receptors linked to phospholipase C (PLC) have provided conflicting results regarding the role of second messenger-dependent (i.e., protein kinase A or C) and -independent (i.e., beta-adrenergic receptor kinase) kinases in mediating this process. Recent results for truncated and mutated gastrin-releasing peptide (GRP) receptors (GRP-R), as well as muscarinic cholinergic receptors, suggest that activation of protein kinase C may be needed for full receptor internalization. Nearly all G protein-coupled receptors studied to date, including the GRP-R, possess two highly conserved amino acids that are important in mediating receptor-G protein coupling to second messengers, i.e., arginine in the proximal second intracellular loop and alanine in the distal third intracellular loop. We selectively mutated each of these residues in the GRP-R to determine their importance for activation of PLC. Site-directed mutagenesis was performed to change arginine at position 139 to glycine (R139G mutant) and alanine at position 263 to glutamate (A263E mutant), with stable cell lines being created by transfection of the wild-type or mutated receptor cDNA into BALB/3T3 fibroblasts. Both R139G (K-d = 12.0 +/- 1.6 nM) and A263E (K-d = 12.2 +/- 1.7 nM) had a lower affinity for bombesin than did wild-type GRP-R (K-d = 1.4 +/- 0.4 nM); however, characteristic stoichiometries for the binding of agonists to this receptor were maintained equally in all three cell lines (bombesin > GRP much greater than neuromedin B). The wild-type GRP-R exposed to bombesin increased [H-3]inositol phosphates (a measure of PLC activation) approximately 4-fold, with an EC(50) of 5.1 +/- 2.2 nM. In contrast, [H-3]inositol phosphates were not significantly increased in cells expressing R139G or A263E receptors, demonstrating that Arg(139) and Ala(263) are required for GRP-R activation of PLC. However, when receptor internalization at 37 degrees was assessed by ligand acid-stripping studies, 53 +/- 2% of A263E receptors were internalized at 90 min, compared with 85 +/- 5% of wild-type GRP-R, whereas only 10 +/- 3% of R139G receptors were internalized. Preincubation of either mutant cell line with 100 nM 12-O-tetradecanoylphorbol-13-acetate markedly increased internalization rates, such that at 90 min 62 +/- 2% of R139G receptors and 82 +/- 1% of A263E receptors were internalized. To assess receptor-G protein coupling, membranes from all three cell lines were incubated with I-125-[Tyr(4)]bombesin and guanosine-5'-(beta,gamma-imido)triphosphate, a non hydrolyzable guanine nucleotide analogue. Increasing concentrations of guanosine-5'-(beta,gamma-imido)triphosphate decreased I-125-[Tyr(4)]bombesin binding to wild-type GRP-R and A263E, but there was little effect on binding to R139G. Thus, internalization of the GRP-R requires intact receptor-G protein coupling, whereas activation of PLC is not essential. These results, coupled with previous studies showing less than complete internalization when a protein kinase C site in the GRP-R tail was mutated, suggest that both PLC-dependent and -independent pathways are important in mediating GRP-R internalization. C1 NCI,BIOL CHEM LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892. NR 64 TC 41 Z9 41 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 SEP PY 1994 VL 46 IS 3 BP 495 EP 501 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PJ601 UT WOS:A1994PJ60100013 PM 7935330 ER PT J AU PINTO, JC POTIE, F RICE, KC BORING, D JOHNSON, MR EVANS, DM WILKEN, GH CANTRELL, CH HOWLETT, AC AF PINTO, JC POTIE, F RICE, KC BORING, D JOHNSON, MR EVANS, DM WILKEN, GH CANTRELL, CH HOWLETT, AC TI CANNABINOID RECEPTOR-BINDING AND AGONIST ACTIVITY OF AMIDES AND ESTERS OF ARACHIDONIC-ACID SO MOLECULAR PHARMACOLOGY LA English DT Article ID ADENYLATE-CYCLASE; RAT-BRAIN; ANANDAMIDE; IDENTIFICATION; INHIBITORS; MEMBRANES; HYDROLASE AB The cannabinoid receptor in brain (CB1) specifically binds Delta(9)-tetrahydrocannabinol, the predominant central nervous system-active component of marijuana. An eicosanoid found in brain, N-(2-hydroxyethyl)arachidonylamide (anandamide), binds to CB1 with similar affinity. This report considers structure-activity requirements for a series of novel amides and rigid hairpin conformations typified by N-(2-hydroxyethyl)prostaglandin amides, assayed with phenylmethylsulfonyl fluoride inactivation of esterases/amidases. Arachidonyl esters were 30-fold less potent than N-(2-hydroxyethyl)arachidonylamide, showing a rank order of potency of methyl = ethyl > propyl = isopropyl, Within the N-(hydroxyalkyl)arachidonylamide series, a one-carbon increase in chain length increased the potency e-fold, but continued extension decreased affinity. Substituting the amide for the N-(2-hydroxyethylamide function produced a 4-fold loss of affinity. The N-(propyl)-, N-(butyl)-, and N-(Benzyl)arachidonylamide derivatives exhibited a 3-fold increase, no change, and a 5-fold decrease, respectively, in affinity, Compared with N-(2-hydroxyethyl)arachidonylamide. Both the methoxy ether and the formamide derivatives suffered > 20-fold loss of potency, compared with N-(2-hydroxyethyl)arachidonylamide. N-(2-Aminoethyl)arachidonylamide interacted poorly with CB1. At 100 mu M, N-(2-hydroxyethyl)amide analogs of prostaglandin E(2), A(2), B-2, and B-1 failed to alter [H-3]CP55940 binding to CB1. N-(2-Hydroxyethyl)arachidonylamide inhibited adenylate cyclase with lesser potency but with similar efficacy, compared with desacetyllevon-antradol. Extending the length of the hydroxyalkyl moiety by one carbon increased the apparent potency by 1 order of magnitude. The N-(propyl) derivative exhibited a 5-fold greater potency than did the N-(2-hydroxyethyl) analog. It appears that the bulk and length of the moiety appended to arachidonic acid are more important determinants of affinity for CB1 than is hydrogen-bonding capability. C1 ST LOUIS UNIV,SCH MED,DEPT PHARMACOL & PHYSIOL SCI,ST LOUIS,MO 63104. NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. US FDA,DIV ANTIVIRAL DRUG PROD,ROCKVILLE,MD 20857. OI Howlett, Allyn/0000-0002-2810-0164 FU NIDA NIH HHS [K05-DA00182, R01-DA03690, R01-DA06912] NR 22 TC 108 Z9 112 U1 1 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 1994 VL 46 IS 3 BP 516 EP 522 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PJ601 UT WOS:A1994PJ60100016 PM 7935333 ER PT J AU DETERAWADLEIGH, SD FANNING, TG AF DETERAWADLEIGH, SD FANNING, TG TI PHYLOGENY OF THE STEROID-RECEPTOR SUPERFAMILY SO MOLECULAR PHYLOGENETICS AND EVOLUTION LA English DT Article ID THYROID-HORMONE RECEPTOR; 9-CIS RETINOIC ACID; HUMAN GLUCOCORTICOID RECEPTOR; VITAMIN-D RECEPTOR; A-I GENE; X-RECEPTOR; TRANSCRIPTION FACTOR; RESPONSE ELEMENTS; NUCLEAR RECEPTOR; GENOMIC ORGANIZATION AB The phylogenetic relationships of 56 nuclear hormone receptors from both invertebrates and vertebrates were determined by the parsimony method (PAUP). The consensus tree suggests that the ancestral gene diverged into five major subfamilies, each of which evolved into at least one cluster of related molecules. These subfamilies are represented by: (i) thyroid hormone receptors (TR); (ii) steroid receptors (SR); (iii) retinoic acid receptors (RAR), retinoid X receptors (RXR), and the chicken ovalbumin upstream promoter transcription factor 1 (COUP) group; (ix) peroxisome proliferator-activated receptors (PPAR); and (v) vitamin D receptor (VDR) and knirps (kni) group. Although the neighbor-joining (N-J) method clustered the receptors into a greater number of subfamilies, it was evident that the components of the terminal receptor subgroups were similar to those found in the PAUP tree. These terminal clusters might then represent phylogenetically stable relationships. The positions of some orphan receptors were perturbed when a different algorithm was employed in the analysis. Both PAUP and N-J evolutionary trees showed that the receptors within the subgroups of a major sublineage tend to recognize hormones of very similar structure. This finding suggests that the relative phylogenetic position of orphans to well-characterized receptors might be exploited to predict the type of ligand they would recognize. C1 NIMH, CLIN NEUROGENET BRANCH, BETHESDA, MD 20892 USA. USA, INST PATHOL, DEPT CELLULAR PATHOL, WASHINGTON, DC 20306 USA. NR 100 TC 29 Z9 30 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1055-7903 EI 1095-9513 J9 MOL PHYLOGENET EVOL JI Mol. Phylogenet. Evol. PD SEP PY 1994 VL 3 IS 3 BP 192 EP 205 DI 10.1006/mpev.1994.1022 PG 14 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA PG448 UT WOS:A1994PG44800002 PM 7820284 ER PT J AU STOPPER, H ECKERT, I SCHIFFMANN, D SPENCER, DL CASPARY, WJ AF STOPPER, H ECKERT, I SCHIFFMANN, D SPENCER, DL CASPARY, WJ TI IS MICRONUCLEUS INDUCTION BY ANEUGENS AN EARLY EVENT LEADING TO MUTAGENESIS SO MUTAGENESIS LA English DT Article ID MOUSE-LYMPHOMA-CELLS; TK-/ MUTANTS; THYMIDINE KINASE LOCUS; MAMMALIAN-CELLS; TRIFLUOROTHYMIDINE-RESISTANT; L5178Y/TK+/ MOUSE; CODED CHEMICALS; MUTATION ASSAY; CHROMOSOME ANALYSIS; MUTAGENICITY AB This study was designed to investigate a previously unidentified potential mechanism for mutation induction as well as to clarify a biological consequence of micronucleus formation. We compared the induction of micronuclei with mutation induction as measured by trifluorothymidine (TFT) resistance in mouse L5178Y cells using four aneugens: colcemid, diethylstilbestrol, griseofulvin and vinblastine. All four compounds induced micronuclei which appeared in the first cell cycle after treatment. More than 85% of the micronuclei induced by each compound stained positive for the presence of kinetochores implying that the micronuclei contained whole chromosomes. However, these same compounds were unable to induce TFT resistance under three different treatment regimes. We concluded that these compounds, under conditions where they induce primarily kinetochore positive micronuclei, were not able to induce mutations. Thus, the induction of micronuclei containing whole chromosomes harboring a selectable gene is not an early event leading to mutations in these cells. C1 UNIV ROSTOCK,INST ANIM PHYSIOL,D-18051 ROSTOCK,GERMANY. NIH,ENVIRONM CARCINOGENESIS & MUTAGENESIS LAB,RES TRIANGLE PK,NC 27709. RP STOPPER, H (reprint author), UNIV WURZBURG,INST PHARMACOL & TOXICOL,D-97078 WURZBURG,GERMANY. NR 39 TC 31 Z9 31 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD SEP PY 1994 VL 9 IS 5 BP 411 EP 416 DI 10.1093/mutage/9.5.411 PG 6 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA PJ862 UT WOS:A1994PJ86200004 PM 7837974 ER PT J AU ZEIGER, E GULATI, DK KAUR, P MOHAMED, AH REVAZOVA, J DEATON, TG AF ZEIGER, E GULATI, DK KAUR, P MOHAMED, AH REVAZOVA, J DEATON, TG TI CYTOGENETIC STUDIES OF SODIUM-FLUORIDE IN MICE SO MUTAGENESIS LA English DT Article ID MICRONUCLEUS TEST; PLASMA AB The cytogenetic effects of sodium fluoride (NaF) were measured in mice following administration in the drinking water for 6 weeks. Bone fluoride levels were determined and showed a dose-related incorporation of fluoride. Micronuclei were measured in peripheral blood erythrocytes following 1 and 6 weeks of NaF administration. Bone marrow cell preparations were examined for the presence of chromosome aberrations following 6 weeks of treatment; metaphase and anaphase cells were examined. Anaphase cells were scored in three independent laboratories, two of which also scored metaphase cells from the same slides. No increases in micronuclei were seen in peripheral erythrocytes at either time point, and no increases in chromosome aberrations were seen in bone marrow cells when metaphase or anaphase cells were examined. A concurrent positive control, cyclophosphamide, produced significant increases in peripheral blood cell micronuclei and in chromosome aberrations in bone marrow cells in metaphase. No increases in aberrations were seen in the same cyclophosphamide-treated mice when anaphase cells were examined. C1 ENVIRONM HLTH RES & TESTING INC,LEXINGTON,KY 40503. UNIV MISSOURI,DEPT MOLEC BIOL & BIOCHEM,KANSAS CITY,MO 64110. ALL UNION SCI RES INST PREVENT TOXICOL & DISINFEC,MOSCOW,RUSSIA. UNIV N CAROLINA,SCH DENT,DENT RES CTR,CHAPEL HILL,NC 27599. RP ZEIGER, E (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 17 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD SEP PY 1994 VL 9 IS 5 BP 467 EP 471 DI 10.1093/mutage/9.5.467 PG 5 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA PJ862 UT WOS:A1994PJ86200012 PM 7837981 ER PT J AU TAKAHAMA, Y SUZUKI, H KATZ, KS GRUSBY, MJ SINGER, A AF TAKAHAMA, Y SUZUKI, H KATZ, KS GRUSBY, MJ SINGER, A TI POSITIVE SELECTION OF CD4+ T-CELLS BY TCR LIGATION WITHOUT AGGREGATION EVEN IN THE ABSENCE OF MHC SO NATURE LA English DT Article ID CD3/T-CELL RECEPTOR COMPLEX; CLASS-II MOLECULES; MONOCLONAL-ANTIBODY; ANTIGEN RECEPTOR; IMMATURE THYMOCYTES; NEGATIVE SELECTION; TRANSGENIC MICE; CROSS-LINKING; THYMUS; BETA AB THE developmental fate of immature thymocytes is determined by the specificity of their T-cell antigen receptors (TCRs). Immature CD4(+)8(+) thymocytes are positively selected to differentiate into mature T cells by recognition of peptides associated with major histocompatibility complex (MHC) encoded molecules(7-10) on But neither the identity of molecules transducing positive selection signals nor the nature of the signals themselves is fully known. Here we report that direct ligation of TCR molecules by monoclonal antibodies specific for either clonotypic or CD3 chains can signal immature thymocytes to differentiate into mature CD4(+)8(-) T cells, even in the absence of MHC expression and MHC-dependent CD4 co-receptor signalling. Moreover, we show that TCR engagement induces positive selection signals only in the absence of TCR aggregation and that TCR aggregation is inhibitory for positive selection. Thus, low valency of TCR crosslinking is a critical parameter(15), distinguishing positive selection from other TCR-mediated signalling events. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. SYNTEX INST IMMUNOL,NIIHARI 30041,JAPAN. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT RHEUMATOL,BOSTON,MA 02115. RI Suzuki, Harumi/L-1271-2013 OI Suzuki, Harumi/0000-0003-3616-9361 NR 46 TC 71 Z9 71 U1 1 U2 3 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD SEP 1 PY 1994 VL 371 IS 6492 BP 67 EP 70 DI 10.1038/371067a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PE381 UT WOS:A1994PE38100052 PM 7915400 ER PT J AU HUSSUSSIAN, CJ STRUEWING, JP GOLDSTEIN, AM HIGGINS, PAT ALLY, DS SHEAHAN, MD CLARK, WH TUCKER, MA DRACOPOLI, NC AF HUSSUSSIAN, CJ STRUEWING, JP GOLDSTEIN, AM HIGGINS, PAT ALLY, DS SHEAHAN, MD CLARK, WH TUCKER, MA DRACOPOLI, NC TI GERMLINE P16 MUTATIONS IN FAMILIAL MELANOMA SO NATURE GENETICS LA English DT Article ID DYSPLASTIC NEVUS; LINKAGE; LOCUS AB The p16 gene is located in chromosome 9p21, a region that is linked to familial melanoma and homozygously deleted in many tumour cell lines. We describe eight p16 germline substitutions (one nonsense, one splice donor site and six missense) in 13/18 familiar melanoma kindreds. Six of these mutations were identified in 33/36 melanoma cases in nine families, whereas two were detected in normal controls and are not disease-related. The melanoma-specific mutations were detected in 9p21-linked, but not in 1p36-linked, families, thereby confirming previous reports of genetic heterogeneity. Functional analyses of these mutations will confirm those causally related to the development of familial melanoma. C1 WASHINGTON UNIV,SCH MED,DEPT SURG,ST LOUIS,MO 63110. NCI,GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NIH,NATL CTR HUMAN GENOME RES,GENET DIS RES LAB,BETHESDA,MD 20892. RI Struewing, Jeffery/C-3221-2008; Tucker, Margaret/B-4297-2015; Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 NR 27 TC 1009 Z9 1018 U1 3 U2 10 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 1994 VL 8 IS 1 BP 15 EP 21 DI 10.1038/ng0994-15 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA PE157 UT WOS:A1994PE15700010 PM 7987387 ER PT J AU CRYSTAL, RG MCELVANEY, NG ROSENFELD, MA CHU, CS MASTRANGELI, A HAY, JG BRODY, SL JAFFE, HA EISSA, NT DANEL, C AF CRYSTAL, RG MCELVANEY, NG ROSENFELD, MA CHU, CS MASTRANGELI, A HAY, JG BRODY, SL JAFFE, HA EISSA, NT DANEL, C TI ADMINISTRATION OF AN ADENOVIRUS CONTAINING THE HUMAN CFTR CDNA TO THE RESPIRATORY-TRACT OF INDIVIDUALS WITH CYSTIC-FIBROSIS SO NATURE GENETICS LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; MEDIATED GENE-TRANSFER; CHLORIDE CHANNEL; INTERLEUKIN-6; EXPRESSION; INVIVO; IDENTIFICATION; PATHOGENESIS; TRANSCRIPTS; EPITHELIUM AB We have administered a recombinant adenovirus vector (AdCFTR) containing the normal human CFTR cDNA to the nasal and bronchial epithelium of four individuals with cystic fibrosis (CF). We show that this vector can express the CFTR cDNA in the CF respiratory epithelium in vivo. With doses up to 2 x 10(9) pfu, there was no recombination/ complementation or shedding of the vector or rise of neutralizing antibody titres. At 2 x 10(9) pfu, a transient systemic and pulmonary syndrome was observed, possibly mediated by interleukin-6. Follow-up at 6-12 months demonstrated no long term adverse effects. Thus, it is feasible to use an adenovirus vector to transfer and express the CFTR cDNA in the respiratory epithelium of individuals with CF. Correction of the CF phenotype of the airway epithelium might be achieved with this strategy. C1 NHLBI,PULM BRANCH,BETHESDA,MD 20892. RP CRYSTAL, RG (reprint author), CORNELL UNIV,MED CTR,NEW YORK HOSP,DIV PULM & CRIT CARE MED,520 E 70 ST,ST-505,NEW YORK,NY 10021, USA. RI McElvaney, Noel/A-6809-2010 FU NHLBI NIH HHS [1 P01 HL51746-01] NR 67 TC 686 Z9 691 U1 1 U2 20 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 1994 VL 8 IS 1 BP 42 EP 51 DI 10.1038/ng0994-42 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA PE157 UT WOS:A1994PE15700014 PM 7527271 ER PT J AU SUTCLIFFE, JS NAKAO, M CHRISTIAN, S ORSTAVIK, KH TOMMERUP, N LEDBETTER, DH BEAUDET, AL AF SUTCLIFFE, JS NAKAO, M CHRISTIAN, S ORSTAVIK, KH TOMMERUP, N LEDBETTER, DH BEAUDET, AL TI DELETIONS OF A DIFFERENTIALLY METHYLATED CPG ISLAND AT THE SNRPN GENE DEFINE A PUTATIVE IMPRINTING CONTROL REGION SO NATURE GENETICS LA English DT Article ID PRADER-WILLI SYNDROME; FAMILIAL ANGELMAN SYNDROME; NUCLEAR RIBONUCLEOPROTEIN POLYPEPTIDE; DNA METHYLATION; MOLECULAR DIAGNOSIS; GEL-ELECTROPHORESIS; LINKAGE ANALYSIS; PARENTAL ORIGIN; EXPRESSION; CLONING AB To determine the molecular basis of Prader-Willi syndrome (PWS) and Angelman syndrome (AS), we have isolated new transcripts from chromosome 15q11-q13. Two novel transcripts located within 300 kilobases telomeric to the small nuclear ribonucleoprotein-associated polypeptide N gene (SNRPN) were paternally expressed in cultured cells, along with SNRPN, defining a large imprinted transcriptional domain. In three PWS patients (two sibs), small deletions remove a differentially methylated CpG island containing a newly described 5' exon alpha of SNRPN, and cause loss of expression for the three imprinted transcripts and altered methylation over hundreds of kilobases. The smallest PWS deletion is familial and asymptomatic with maternal transmission. Our data imply the presence of a paternal imprinting control region near exon alpha. C1 BAYLOR COLL MED,HOWARD HUGHES MED INST,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MOLEC & HUMAN GENET,HOUSTON,TX 77030. ULLEVAL UNIV HOSP,DEPT MED GENET,OSLO,NORWAY. JOHN F KENNEDY INST,DANISH CTR HUMAN GENOME RES,DK-2600 GLOSTRUP,DENMARK. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. OI Sutcliffe, James/0000-0001-5200-6007 FU NHGRI NIH HHS [HG00210]; NICHD NIH HHS [HD20619] NR 48 TC 340 Z9 340 U1 0 U2 10 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 1994 VL 8 IS 1 BP 52 EP 58 DI 10.1038/ng0994-52 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA PE157 UT WOS:A1994PE15700015 PM 7987392 ER PT J AU JAMES, MR RICHARD, CW SCHOTT, JJ YOUSRY, C CLARK, K BELL, J TERWILLIGER, JD HAZAN, J DUBAY, C VIGNAL, A AGRAPART, M IMAI, T NAKAMURA, Y POLYMEROPOULOS, M WEISSENBACH, J COX, DR LATHROP, GM AF JAMES, MR RICHARD, CW SCHOTT, JJ YOUSRY, C CLARK, K BELL, J TERWILLIGER, JD HAZAN, J DUBAY, C VIGNAL, A AGRAPART, M IMAI, T NAKAMURA, Y POLYMEROPOULOS, M WEISSENBACH, J COX, DR LATHROP, GM TI A RADIATION HYBRID MAP OF 506 STS MARKERS SPANNING HUMAN-CHROMOSOME-11 SO NATURE GENETICS LA English DT Article ID HUMAN-GENOME-PROJECT; EXPRESSED SEQUENCE TAGS; ALPHA-SATELLITE DNA; HUMAN Y-CHROMOSOME; DISEASE LOCI; TAGGED SITES; GENE; REGION; CLONES; PCR AB We present a high resolution radiation hybrid map-of human chromosome 11 using 506 sequence tagged sites (STSs) scored on a panel of 86 radiation hybrids. The 506 STSs fall into 299 unique positions (average resolution of about 480 kilobases (kb)) that span pericentric markers unambiguously assigned to the short or long arm. The map contains most genes (125) and expressed sequence tags (26) currently assigned to chromosome the whole chromosome. A subset of 260 STSs (143 positions) form a framework map that has a resolution of approximately 1 megabase between adjacent positions and is ordered with odds of at least 1,000:1. The centromere was clearly defined with 11 and more than half of the STSs are polymorphic microsatellite loci. These markers and the map can be used for high resolution physical and genetic mapping. C1 CTR ETUD POLYMORPHISME HUMAIN,PARIS,FRANCE. UNIV PITTSBURGH,DEPT PSYCHIAT,PITTSBURGH,PA 15213. UNIV PITTSBURGH,DEPT HUMAN GENET,PITTSBURGH,PA 15213. JOHN RADCLIFFE HOSP,INST MOLEC MED,OXFORD OX3 9DU,ENGLAND. COLUMBIA UNIV,DEPT GENET & DEV,NEW YORK,NY 10032. INST PASTEUR,CNRS,URA 1445,PARIS,FRANCE. GENETHON,F-91000 EVRY,FRANCE. JAPANESE FDN CANC RES,INST CANC,DEPT BIOCHEM,TOKYO 170,JAPAN. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. STANFORD UNIV,DEPT GENET,STANFORD,CA 94305. INSERM,U358,PARIS,FRANCE. RI Schott, jean-Jacques/F-8842-2013 FU NIMH NIH HHS [MH00802]; Wellcome Trust NR 38 TC 174 Z9 174 U1 0 U2 1 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 1994 VL 8 IS 1 BP 70 EP 76 DI 10.1038/ng0994-70 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA PE157 UT WOS:A1994PE15700018 PM 7987395 ER PT J AU POLYMEROPOULOS, MH SWIFT, RG SWIFT, M AF POLYMEROPOULOS, MH SWIFT, RG SWIFT, M TI LINKAGE OF THE GENE FOR WOLFRAM-SYNDROME TO MARKERS ON THE SHORT ARM OF CHROMOSOME-4 SO NATURE GENETICS LA English DT Article AB Wolfram syndrome is an autosomal recessive disorder defined by the occurrence of diabetes mellitus and progressive bilateral optic atrophy. Wolfram syndrome homozygotes develop widespread nervous system abnormalities; in particular, they exhibit severe behavioural difficulties that often lead to suicide attempts or psychiatric hospitalizations. The Wolfram syndrome gene also predisposes heterozygous carriers to psychiatric disorders, and may contribute significantly to the overall burden of psychiatric illness. Based on a linkage analysis of 11 families segregating for this syndrome using microsatellite repeat polymorphisms throughout the human genome, we found the Wolfram syndrome gene to be linked to markers on the short arm of human chromosome 4, with Z(max) = 6.46 at theta = 0.02 for marker D4S431. C1 NEW YORK MED COLL,INST GENET ANAL COMMON DIS,DEPT PEDIAT,DIV PSYCHIAT GENET,HAWTHORNE,NY 10532. NEW YORK MED COLL,INST GENET ANAL COMMON DIS,DEPT PEDIAT,DIV HUMAN MOLEC GENET,HAWTHORNE,NY 10532. RP POLYMEROPOULOS, MH (reprint author), NIH,NATL CTR HUMAN GENOME RES,GENET DIS RES LAB,BETHESDA,MD 20892, USA. NR 14 TC 110 Z9 113 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 SEP PY 1994 VL 8 IS 1 BP 95 EP 97 DI 10.1038/ng0994-95 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA PE157 UT WOS:A1994PE15700022 PM 7987399 ER PT J AU VUISTER, GW KIM, SJ OROSZ, A MARQUARDT, J WU, C BAX, A AF VUISTER, GW KIM, SJ OROSZ, A MARQUARDT, J WU, C BAX, A TI SOLUTION STRUCTURE OF THE DNA-BINDING DOMAIN OF DROSOPHILA HEAT-SHOCK TRANSCRIPTION FACTOR SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; RESTRAINED MOLECULAR-DYNAMICS; DISTANCE GEOMETRY; CRYSTAL-STRUCTURE; 3-DIMENSIONAL STRUCTURE; PROTEIN; RESOLUTION; REPRESSOR; COMPLEX; RECOGNITION AB The solution structure of the DNA-binding domain of the Drosophila heat shock transcription factor, as determined by multidimensional multinuclear NMR, resembles that of the helix-turn-helix class of DNA-binding proteins. The domain comprises a four-stranded antiparallel beta-sheet, packed against a three-helix bundle. The second helix is significantly distorted and is separated from the third helix by an extended turn which is subject to conformational averaging on an intermediate time scale. Helix 3 forms a classical amphipathic helix with polar and charged residues exposed to the solvent. Upon titration with DNA, resonance shifts in the backbone and Asn and Gln side-chain amides indicate that helix 3 acts as the recognition helix of the heat shock transcription factor. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. UNIV UTRECHT,BIJVOET CTR BIOMOLEC RES,3584 CH UTRECHT,NETHERLANDS. NR 47 TC 79 Z9 81 U1 0 U2 5 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD SEP PY 1994 VL 1 IS 9 BP 605 EP 614 DI 10.1038/nsb0994-605 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA PJ449 UT WOS:A1994PJ44900010 PM 7634100 ER PT J AU CLAUBERG, M SMITH, CB DANG, T SOKOLOFF, L JOSHI, JG AF CLAUBERG, M SMITH, CB DANG, T SOKOLOFF, L JOSHI, JG TI EFFECTS OF CHRONIC DIETARY ALUMINUM ON LOCAL CEREBRAL GLUCOSE-UTILIZATION IN RATS SO NEUROBIOLOGY OF AGING LA English DT Article DE ALUMINUM; AGING; [C-14] DEOXYGLUCOSE ID DIALYSIS ENCEPHALOPATHY; ALZHEIMERS-DISEASE; NEUROFIBRILLARY DEGENERATION; BRAIN; ACCUMULATION; INTOXICATION; HYDROXIDE; DEMENTIA AB Beginning at 4 weeks of age normal, mate, Sprague-Dawley rats were reared on Purina Laboratory Chow and drinking water containing 100 mu M ALCL(3). After 2 years, local rates of cerebral glucose utilization were determined with the autoradiographie [14C] deoxyglucose method in the brain as a whole and in 25 brain regions in 6 treated rats and 4 age-matched controls. The results indicate that any effects of chronic aluminum in the diet on rates of cerebral glucose utilization are small. In the brain as a whole, the mean rate of glucose utilization in the aluminum-treated rats was 6% lower than that of the controls (p = 0.09). In 21 of the 25 brain regions examined mean rates of glucose utilization were generally lower in the aluminum-treated rats but in none of the regions were the effects statistically significant. C1 UNIV TENNESSEE,DEPT BIOCHEM,KNOXVILLE,TN 37996. US PHS,NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. NR 37 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD SEP-OCT PY 1994 VL 15 IS 5 BP 657 EP 661 DI 10.1016/0197-4580(94)00061-1 PG 5 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA PE996 UT WOS:A1994PE99600009 PM 7824059 ER PT J AU NI, Q XU, H PARTILLA, JS DECOSTA, BR RICE, KC BORSODI, A HOSZTAFI, S ROTHMAN, RB AF NI, Q XU, H PARTILLA, JS DECOSTA, BR RICE, KC BORSODI, A HOSZTAFI, S ROTHMAN, RB TI DIHYDROCODEINONE-HYDRAZONE, DIHYDROCODEINONE-OXIME, NALOXONE-3-OME-OXIME, AND CLOCINNAMOX FAIL TO IRREVERSIBLY INHIBIT OPIOID KAPPA-RECEPTOR-BINDING SO NEUROCHEMICAL RESEARCH LA English DT Article DE OPIOID KAPPA RECEPTOR; DIHYDROCODEINONE-HYDRAZONE; DIHYDROCODEINONE-OXIME; NALOXONE-3-OME-OXIME ID GUINEA-PIG BRAIN; BOVINE ADRENAL-MEDULLA; RAT-BRAIN; OPIATE RECEPTORS; AFFINITY STATES; SITES; PEPTIDES; NUCLEOTIDES; DRUGS; HETEROGENEITY AB Previous work from our lab identified two subtypes of the opioid kappa receptor. Whereas the kappa, receptor can be labeled by [H-3]U69,593 (5 alpha,7 alpha,8 beta-(-)-N-methyl-N-[7-(1-pyrrolidinyl)-1- oxaspiro(4,5)dec-8-yl]-phenyl-benzeneacetamide), the kappa(2) receptor can be labeled by [I-125]IOXY (6 beta-(125)iodo-3,14-dihydroxy-17-cyclopropylmethyl-4,5 alpha-epoxymorphinan). Other data demonstrate that [I-125]IOXY, like [H-3]bremazocine, labels two populations of kappa2 receptors in guinea pig brain: kappa(2a) and kappa(2b) binding sites. In the present study, we tested the hypothesis that certain dihydrocodeinone and oxicodone derivatives, which have been shown to irreversibly block low affinity [H-3]naloxone binding sites, would also bind irreversibly to opioid kappa receptor subtypes. We also tested the novel irreversible mu receptor antagonist, clocinnamox (14 beta-(p-chlorocinnamoylamino)-7,8-dihydro-N-cyclopropylmeth mesylate). Wash-resistant inhibition (WRI) assays were conducted to detect apparent irreversible inhibition. The proportion of WRI attribuable to inhibition of receptor binding, termed receptor inhibition (RI), was calculated by the equation: RI = WRI (wash-resistant inhibition) - SI (supernatant inhibition or inhibition attributable to residual drug.) Dihydrocodeinone-hydrazone, dihydrocodeinone-oxime and naloxone-3-OMeoxime failed to produce any wash-resistant inhibition of kappa receptor binding. In contrast, preincubating guinea pig membranes with 1 mu M clocinnamox produced a substantial degree of wash-resistant inhibition (greater than 90%) at kappa(1) and kappa(2) binding sites. However, as indicated by supernatant inhibition values of 70% to 90%, there was a large amount of residual clocinnamox which remained despite the use of an extensive washing procedure. Thus, it is apparent that clocinnamox has essentially no irreversible effect on kappa binding sites. Moreover, these results clearly demonstrate the requirement to determine supernatant inhibition when testing putative irreversible ligands. The apparent inactivity of dihydrocodeinone-hydrazone, dihydrocodeinone-oxime or naloxone-3-OMe-oxime as irreversible inhibitors of kappa receptors suggests that the low affinity [H-3]naloxone binding site eliminated by these agents may not be a kappa binding site. C1 NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD 21224. NIDDK,MED CHEM LAB,BETHESDA,MD 20892. HUNGARIAN ACAD SCI,BIOL RES CTR,INST BIOCHEM,H-6701 SZEGED,HUNGARY. ALKALOIDA CHEM CO,H-4440 TISZAVASCARI,HUNGARY. NR 37 TC 2 Z9 2 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD SEP PY 1994 VL 19 IS 9 BP 1159 EP 1163 DI 10.1007/BF00965150 PG 5 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA PF101 UT WOS:A1994PF10100009 PM 7824069 ER PT J AU CHANG, MCJ WAKABAYASHI, S BELL, JM AF CHANG, MCJ WAKABAYASHI, S BELL, JM TI THE EFFECT OF METHYL PALMOXIRATE ON INCORPORATION OF [U-C-14]PALMITATE INTO RAT-BRAIN SO NEUROCHEMICAL RESEARCH LA English DT Article DE METHYL PALMOXIRATE; PALMITATE; FATTY ACIDS; PHOSPHOLIPIDS; BRAIN; RAT; IN VIVO IMAGING; BETA-OXIDATION INHIBITION; PHOSPHOLIPIDS; METABOLISM ID FATTY-ACID OXIDATION; CEREBRAL PALMITATE INCORPORATION; CARNITINE PALMITOYLTRANSFERASE; UNANESTHETIZED RATS; 2-TETRADECYLGLYCIDIC ACID; HYPOGLYCEMIC AGENT; PLASMA PALMITATE; TURNOVER; INHIBITION AB We examined the dose response, time course and reversibility of the effect of methyl 2-tetradecylglycidate (McN-3716, methyl palmoxirate or MEP), an inhibitor of beta-oxidation of fatty acids, on incorporation of radiolabeled palmitic acid ([U-C-14]PA) from plasma into brain lipids of awake rats. MEP (0.1, 1 and 10 mg/kg) or vehicle was administered intravenously from 10 min to 72 hr prior to infusion of [U-C-14]PA. Two hr pretreatment with MEP (0.1 to 10 mg/kg) increased brain organic radioactivity 1.2 to 1.8 fold and decreased brain aqueous radioactivity by 1.2 to 3.0 fold when compared to control values. At 10 mg/kg, MEP significantly increased brain organic fraction from 40% in controls to 85%, 30 min to 6 hr pretreatment, and resulted in a redistribution of the radiolabeled fatty acid toward triacylglycerol. MEP changed the lipid/aqueous brain ratio of incorporated [U-C-14]PA from 0.67 to 5.7. The incorporation rate coefficient, k*, was significantly increased by MEP (10 mg/kg) at 2 hr (31%), 4 hr (59%) and 6 hr (34%). All effects were reversed by 72 hr, consistent with a half-life of similar to 2 days for carnitine palmitoyl transferase I. These results indicate that intravenous MEP may be used with [1-C-11]palmitic acid for studying brain lipid metabolism in vivo by positron emission tomography, as it significantly reduces the large unincorporated aqueous fraction that would result in high background radioactivity. RP CHANG, MCJ (reprint author), NIA,NEUROSCI LAB,BLDG 10,ROOM 6C103,BETHESDA,MD 20892, USA. NR 27 TC 13 Z9 13 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD SEP PY 1994 VL 19 IS 9 BP 1217 EP 1223 DI 10.1007/BF00965159 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA PF101 UT WOS:A1994PF10100018 PM 7824078 ER PT J AU HIGGINS, JJ KANESKI, CR BERNARDINI, I BRADY, RO BARTON, NW AF HIGGINS, JJ KANESKI, CR BERNARDINI, I BRADY, RO BARTON, NW TI PYRIDOXINE-RESPONSIVE HYPER-BETA-ALANINEMIA ASSOCIATED WITH COHENS SYNDROME SO NEUROLOGY LA English DT Article ID CARNITINE; BRAIN; TRANSAMINASE; DEFICIENCY; GLYCINE; ACIDS; RAT AB We report intermittent seizures, lethargy, and Cohen's syndrome in a 4-year-old girl with hyper-beta-alaninemia and a partial deficiency of beta-alanyl-alpha-ketoglutarate transaminase (AKT). To examine the role of beta-alanine (beta ALA) in cellular metabolism, we cultured her skin fibroblasts in medium containing increasing amounts of beta ALA. At concentrations of 10 to 25 mM, beta ALA caused more than a 50% reduction in the growth of her cells compared with normal control skin fibroblasts. The addition of 0.1 mM of pyridoxine to the culture medium abolished these toxic effects and increased her skin fibroblast AKT enzyme activity more than twofold. During a 2-year period of clinical observation, there were no further episodes of seizures or somnolence in our patient while she received oral pyridoxine therapy. C1 NINCDS,DEV & METAB NEUROL BRANCH,BETHESDA,MD 20892. NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. RP HIGGINS, JJ (reprint author), NINCDS,CLIN NEUROSCI BRANCH,CLIN NEUROGENET UNIT,BLDG 10,ROOM 5N214,BETHESDA,MD 20892, USA. OI Kaneski, Christine/0000-0003-1453-2502 NR 23 TC 17 Z9 17 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP PY 1994 VL 44 IS 9 BP 1728 EP 1732 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA PG390 UT WOS:A1994PG39000033 PM 7936305 ER PT J AU HEIDBREDER, CA SHIPPENBERG, TS AF HEIDBREDER, CA SHIPPENBERG, TS TI U-69593 PREVENTS COCAINE SENSITIZATION BY NORMALIZING BASAL ACCUMBENS DOPAMINE SO NEUROREPORT LA English DT Article DE KAPPA OPIOID; DOPAMINE; NUCLEUS ACCUMBENS; BEHAVIORAL SENSITIZATION; MICRODIALYSIS; COCAINE ID BEHAVIORAL SENSITIZATION; EXTRACELLULAR DOPAMINE; NUCLEUS-ACCUMBENS; KAPPA-OPIOIDS; RELEASE; RAT; TRANSMISSION; INVOLVEMENT; MODULATION; DELTA AB REPEATED intermittent administration of cocaine (20 mg kg(-1), i.p.) for 3 days dramatically increased basal dopamine (DA) overflow in the nucleus accumbens (ACB) 48 h after the final daily injection. This cocaine pretreatment also produced a significant increase in stereotypy in response to a subsequent cocaine challenge. However, when the selective kappa-opioid receptor agonist U-69593 was administered in combination with cocaine for 3 days, these cocaine-induced biochemical and behavioral effects were abolished. It is suggested that the responsiveness of mesolimbic DA neurons to cocaine is intimately related to basal DA concentrations within the ACB and that U-69593, by normalizing cocaine-induced increases in basal DA overflow, may prevent the development of behavioral sensitization to cocaine. RP HEIDBREDER, CA (reprint author), NIDA,ADDICT RES CTR,INTRAMURAL RES PROGRAM,PRECLIN PHARMACOL LAB,POB 5180,BALTIMORE,MD 21224, USA. NR 23 TC 61 Z9 61 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD SEP PY 1994 VL 5 IS 14 BP 1797 EP 1800 DI 10.1097/00001756-199409080-00028 PG 4 WC Neurosciences SC Neurosciences & Neurology GA PG392 UT WOS:A1994PG39200028 PM 7827335 ER PT J AU FAN, P AF FAN, P TI FACILITATION OF 5-HYDROXYTRYPTAMINE(3) RECEPTOR DESENSITIZATION BY FLUOXETINE SO NEUROSCIENCE LA English DT Article ID MEDIATED ION CURRENT; N1E-115 NEUROBLASTOMA-CELLS; SUPERIOR CERVICAL-GANGLION; HUMAN-BRAIN INVITRO; 5-HT3 RECEPTORS; SELECTIVE INHIBITOR; ADULT-RAT; SEROTONIN; ANTIDEPRESSANTS; ANTAGONISTS AB Effect of fluoxetine on the desensitization of the inward current mediated by 5-hydroxytryptamine(3) receptors in rat nodose ganglion neurons was investigated with whole cell patch-clamp recording. 5-Hydroxytryptamine(3) current desensitization was best fitted in most experiments by a single exponential function and showed little dependence on membrane potential. Fluoxetine greatly facilitated the rate of 5-hydroxytryptamine, current desensitization in a dose-dependent manner. The effect of fluoxetine was gradual, long-lasting, voltage-independent and the recovery was incomplete. The IC50 value for the decrease of the desensitization time-constant by fluoxetine was 0.171 mu M and the Hill coefficient was 1.1. Fluoxetine also inhibited the peak and steady-state 5-hydroxytryptamine, current with the latter being more sensitive to fluoxetine. The IC50 value for the effect of fluoxetine on peak current was 1.27 mu M and that on steady-state current was 0.172 mu M. There is a highly significant correlation between the two effects of fluoxetine on current desensitization and on current amplitudes: r-values for the correlation between the decrease in time-constant and the reduction in peak and steady-state current amplitudes were 0.82 and 0.88, respectively (P < 0.001). This action of fluoxetine on 5-hydroxytryptamine, receptors may be involved in the behavioral effects of fluoxetine. RP FAN, P (reprint author), NIAAA,NEUROBIOL CELLULAIRE & MOLEC LAB,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 40 TC 14 Z9 14 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD SEP PY 1994 VL 62 IS 2 BP 515 EP 522 DI 10.1016/0306-4522(94)90384-0 PG 8 WC Neurosciences SC Neurosciences & Neurology GA PJ331 UT WOS:A1994PJ33100019 PM 7830894 ER PT J AU SCHULKIN, J MCEWEN, BS GOLD, PW AF SCHULKIN, J MCEWEN, BS GOLD, PW TI ALLOSTASIS, AMYGDALA, AND ANTICIPATORY ANGST SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE AMYGDALA; ALLOSTASIS; PSYCHOPATHOLOGY ID CORTICOTROPIN-RELEASING-FACTOR; CENTRAL NUCLEUS LESIONS; GLUCOCORTICOID RECEPTOR IMMUNOREACTIVITY; MESSENGER-RNA EXPRESSION; ACOUSTIC STARTLE REFLEX; CENTRAL NERVOUS-SYSTEM; PARAVENTRICULAR NUCLEUS; IMMOBILIZATION-STRESS; RAT-BRAIN; BIOCHEMICAL MANIFESTATIONS AB Regions of the amygdala are involved in anticipation of negative events. Chronic anticipation of negative events leads to what we call allostatic load, or arousal pathology. Two hormones appear to be involved in arousal pathology; corticotropin-releasing hormone in the brain and glucocorticoids. We suggest that increases in corticotropin-releasing hormone, by stress or glucocorticoids, in the amygdala may have functional consequences for allostatic load. Whereas, corticotropin-releasing hormone in the parvocellular region of the paraventricular nucleus of the hypothalamus is decreased by glucocorticoids thereby under negative feedback and homeostatic control, the central nucleus of the amygdala is to some extent under positive feedback and is increased by glucocorticoids, and perhaps under allostatic control. The human and animal literature suggest that a variety of psychopathologies (e.g., melancholia) may be tied to neurohormonal signals activating regions of the amygdala. C1 ROCKEFELLER UNIV,DEPT NEUROENDOCRINOL,NEW YORK,NY. RP SCHULKIN, J (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,BEHAV NEUROSCI UNIT,BLDG 10,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 165 TC 217 Z9 219 U1 5 U2 19 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0149-7634 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PD FAL PY 1994 VL 18 IS 3 BP 385 EP 396 DI 10.1016/0149-7634(94)90051-5 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA PB827 UT WOS:A1994PB82700008 PM 7984356 ER PT J AU KRASNEGOR, NA OTTO, DA BERNSTEIN, JH BURKE, R CHAPPELL, W ECKERMAN, DA NEEDLEMAN, HL OAKLEY, G ROGAN, W TERRACCIANO, G HUTCHINSON, L AF KRASNEGOR, NA OTTO, DA BERNSTEIN, JH BURKE, R CHAPPELL, W ECKERMAN, DA NEEDLEMAN, HL OAKLEY, G ROGAN, W TERRACCIANO, G HUTCHINSON, L TI NEUROBEHAVIORAL TEST STRATEGIES FOR ENVIRONMENTAL EXPOSURES IN PEDIATRIC POPULATIONS SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE PEDIATRIC RESEARCH; BEHAVIORAL TESTING; ENVIRONMENTAL TOXICOLOGY; NEUROTERATOLOGY; ATSDR ID LEAD-EXPOSURE; PERFORMANCE; CHILDREN; SYSTEM AB The Agency for Toxic Substances and Disease Registry convened a workshop in Atlanta, GA, that evaluated approaches and methods to ascertain whether there are neurobehavioral sequelae to children and adults exposed to hazardous substances in the environment. This article, developed from that workshop, addresses the feasibility of employing extant neurobehavioral tests to screen pediatric populations. A matrix lists basic functions to be assessed during eight developmental periods ranging from birth to high school. The best of these neurobehavioral tests for pediatric populations and the types of assessment tools that are still needed are discussed. We make 10 specific recommendations to establish a hazardous substances neurobehavioral screen for pediatric populations, including appointing a review panel, developing a structured questionnaire, convening a conference on design and analysis, addressing minority and socially disadvantaged populations, coordinating adult and child assessment methods, information sharing among Federal agencies, baseline data, methodology research, research associated with hazardous worksites, and establishment of a pediatric databank. C1 US EPA,RES TRIANGLE PK,NC 27599. CHILDRENS HOSP,BOSTON,MA 02115. US COAST GUARD ACAD,NEW LONDON,CT 06320. UNIV COLORADO,DENVER,CO 80217. UNIV N CAROLINA,CHAPEL HILL,NC 27599. UNIV PITTSBURGH,PITTSBURGH,PA 15213. NIEHS,RES TRIANGLE PK,NC 27709. AGCY TOX SUBST & DIS REGISTRY,ATLANTA,GA 30333. NATL CTR ENVIRONM HLTH & INJURY CONTROL,ATLANTA,GA 30333. RP KRASNEGOR, NA (reprint author), NICHHD,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 NR 40 TC 23 Z9 23 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD SEP-OCT PY 1994 VL 16 IS 5 BP 499 EP 509 DI 10.1016/0892-0362(94)90129-5 PG 11 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA PG379 UT WOS:A1994PG37900008 PM 7845333 ER PT J AU BRITTENHAM, GM GRIFFITH, PM NIENHUIS, AW MCLAREN, CE YOUNG, NS TUCKER, EE ALLEN, CJ FARRELL, DE HARRIS, JW AF BRITTENHAM, GM GRIFFITH, PM NIENHUIS, AW MCLAREN, CE YOUNG, NS TUCKER, EE ALLEN, CJ FARRELL, DE HARRIS, JW TI EFFICACY OF DEFEROXAMINE IN PREVENTING COMPLICATIONS OF IRON OVERLOAD IN PATIENTS WITH THALASSEMIA MAJOR SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CHELATION-THERAPY; CARDIAC-FUNCTION; DESFERRIOXAMINE; STORES; ANEMIA; SURVIVAL AB Background. To determine whether deferoxamine prevents the complications of transfusional iron overload in thalassemia major, we evaluated 59 patients (30 were female and 29 male; age range, 7 to 31 years) periodically for 4 to 10 years or until death. Methods. At each follow-up visit, we performed a detailed clinical and laboratory evaluation and measured hepatic iron stores with a noninvasive magnetic device. Results. The body iron burden as assessed by magnetic measurement of hepatic iron stores was closely correlated (R = 0.89, P < 0.001) with the ratio of cumulative transfusional iron load to cumulative deferoxamine use (expressed in millimoles of iron per kilogram of body weight, in relation to grams of deferoxamine per kilogram, transformed into the natural logarithm). Each increase of one unit in the natural logarithm of the ratio (transfusional iron load to deferoxamine use) was associated with an increased risk of impaired glucose tolerance (relative risk, 19.3; 95 percent confidence interval, 4.8 to 77.4), diabetes mellitus (relative risk, 9.2; 95 percent confidence interval, 1.8 to 47.7), cardiac disease (relative risk, 9.9; 95 percent confidence interval, 1.9 to 51.2), and death (relative risk, 12.6; 95 percent confidence interval, 2.4 to 65.4). All nine deaths during the study occurred among the 23 patients who had begun chelation therapy later and used less deferoxamine in relation to their transfusional iron load (P < 0.001). Conclusions. The early use of deferoxamine in an amount proportional to the transfusional iron load reduces the body iron burden and helps protect against diabetes mellitus, cardiac disease, and early death in patients with thalassemia major. C1 CASE WESTERN RESERVE UNIV, DEPT MED, CLEVELAND, OH 44106 USA. CASE WESTERN RESERVE UNIV, DEPT PHYS, CLEVELAND, OH 44106 USA. MOORHEAD STATE UNIV, DEPT MATH, MOORHEAD, MN 56560 USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38105 USA. NHLBI, CLIN HEMATOL BRANCH, BETHESDA, MD 20892 USA. NHLBI, CARDIOL BRANCH, BETHESDA, MD 20892 USA. FU FDA HHS [FD-U-000532]; NIADDK NIH HHS [AM-25105]; NIDDK NIH HHS [DK-14370] NR 32 TC 545 Z9 554 U1 2 U2 8 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 1 PY 1994 VL 331 IS 9 BP 567 EP 573 DI 10.1056/NEJM199409013310902 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA PD699 UT WOS:A1994PD69900002 PM 8047080 ER PT J AU HEINONEN, OP HUTTUNEN, JK ALBANES, D TAYLOR, PR AF HEINONEN, OP HUTTUNEN, JK ALBANES, D TAYLOR, PR TI BETA-CAROTENE, VITAMIN-E, AND LUNG-CANCER - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NCI,BETHESDA,MD 20892. RP HEINONEN, OP (reprint author), NATL PUBL HLTH INST,SF-00300 HELSINKI,FINLAND. RI Albanes, Demetrius/B-9749-2015 NR 1 TC 1 Z9 1 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 1 PY 1994 VL 331 IS 9 BP 613 EP 613 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PD699 UT WOS:A1994PD69900018 ER PT J AU BLOT, WJ LI, JY TAYLOR, PR LI, B AF BLOT, WJ LI, JY TAYLOR, PR LI, B TI LUNG-CANCER AND VITAMIN SUPPLEMENTATION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 CHINESE ACAD MED SCI,BEIJING 100021,PEOPLES R CHINA. RP BLOT, WJ (reprint author), NCI,BETHESDA,MD 20892, USA. NR 3 TC 30 Z9 31 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 1 PY 1994 VL 331 IS 9 BP 614 EP 614 DI 10.1056/NEJM199409013310913 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PD699 UT WOS:A1994PD69900020 PM 8047094 ER PT J AU TAITELBAUM, H WEISS, GH SPENCER, RGS AF TAITELBAUM, H WEISS, GH SPENCER, RGS TI OPTIMIZATION OF MAGNETIZATION-TRANSFER EXPERIMENTS FOR KINETIC RATE MEASUREMENTS SO NMR IN BIOMEDICINE LA English DT Article ID KINASE REACTION-RATES; SATURATION-TRANSFER; HUMAN-BRAIN; P-31 NMR; HEART; INVIVO; RESONANCE AB A framework is developed for optimizing magnetization transfer experiments for measuring first-order rate constants of a two-component exchange network. In the analysis the spin-lattice relaxation time of the nonsaturated resonance is assumed to be known. However, we demonstrate that our work can also be applied to cases in which the spin-lattice relaxation time falls within a physiologically reasonable range for this parameter. We provide an algorithm for the parameters permitting the experimenter to optimize the selection of measurement times in order to control the error in a worst-case scenario. In addition, we compare the performance of the time-dependent saturation experiment with an inversion experiment in this framework, finding that the former always leads to a more effective design. C1 NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. BAR ILAN UNIV,JEROME SCHOTTENSTEIN CELLSCAN CTR,IL-52100 RAMAT GAN,ISRAEL. BAR ILAN UNIV,DEPT PHYS,IL-52100 RAMAT GAN,ISRAEL. NIA,MOLEC & CELLULAR BIOL LAB,BALTIMORE,MD 21224. NR 22 TC 6 Z9 6 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD SEP PY 1994 VL 7 IS 6 BP 287 EP 292 DI 10.1002/nbm.1940070606 PG 6 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA PP010 UT WOS:A1994PP01000005 PM 7841025 ER PT J AU BENSON, DA BOGUSKI, M LIPMAN, DJ OSTELL, J AF BENSON, DA BOGUSKI, M LIPMAN, DJ OSTELL, J TI GENBANK SO NUCLEIC ACIDS RESEARCH LA English DT Article ID EXPRESSED SEQUENCE TAGS; HUMAN GENOME AB The GenBank sequence database continues to expand its data coverage, quality control, annotation content and retrieval services for the scientific community. Besides handling direct submissions of sequence data from authors, GenBank also incorporates DNA sequences from all available public sources; an integrated retrieval system, known as Entrez, also makes available data from the major protein sequence and structural databases, and from U.S. and European patents. MEDLINE abstracts from published articles describing the sequences are also included as an additional source of biological annotation for sequence entries. GenBank supports distribution of the data via FTP, CD-ROM, and E-mail servers. Network server-client programs provide access to an integrated database for literature retrieval and sequence similarity searching. RP BENSON, DA (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,GENBANK,BLDG 38A,RM 8S-803,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 5 TC 165 Z9 168 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP PY 1994 VL 22 IS 17 BP 3441 EP 3444 DI 10.1093/nar/22.17.3441 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PJ873 UT WOS:A1994PJ87300001 PM 7937042 ER PT J AU HOLLSTEIN, M RICE, K GREENBLATT, MS SOUSSI, T FUCHS, R SORLIE, T HOVIG, E SMITHSORENSEN, B MONTESANO, R HARRIS, CC AF HOLLSTEIN, M RICE, K GREENBLATT, MS SOUSSI, T FUCHS, R SORLIE, T HOVIG, E SMITHSORENSEN, B MONTESANO, R HARRIS, CC TI DATABASE OF P53 GENE SOMATIC MUTATIONS IN HUMAN TUMORS AND CELL-LINES SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SUPPRESSOR GENE; DNA; REPAIR AB A data base is described in which over 2,500 mutations in the p53 gene of human tumors and tumor cell lines are compiled from a systematic search of reports published before 1 January 1994. Data from 1994 are being added intermittently, with a systematic search and update scheduled for December, 1994. The compilation has been deposited with the EMBL Data Library and is available in electronic form free of charge. This report contains a rationale for the compilation, a brief summary of the major findings and a description of the data base. C1 INT AGCY RES CANC,F-69372 LYON 08,FRANCE. EUROPEAN MOLEC BIOL LAB,D-69120 HEIDELBERG,GERMANY. INST GENET MOLEC,INSERM,U301,F-75010 PARIS,FRANCE. NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. NORWEGIAN RADIUM HOSP,INST CANC RES,N-0310 OSLO,NORWAY. RP HOLLSTEIN, M (reprint author), GERMAN CANC RES CTR,NEUENHEIMER FELD 280,D-69120 HEIDELBERG,GERMANY. RI Hovig, Eivind/H-2474-2011; Sorlie, Therese/B-1413-2015; OI Hovig, Eivind/0000-0002-9103-1077; Sorlie, Therese/0000-0002-5995-2319; Fuchs, Rainer/0000-0001-8110-5186; soussi, thierry/0000-0001-8184-3293 NR 16 TC 738 Z9 753 U1 1 U2 9 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP PY 1994 VL 22 IS 17 BP 3551 EP 3555 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PJ873 UT WOS:A1994PJ87300020 PM 7937055 ER PT J AU PALMER, S AF PALMER, S TI ANTIOXIDANT VITAMINS AND CANCER RISK SO NUTRITION LA English DT Editorial Material ID EPIDEMIOLOGIC EVIDENCE; SERUM SELENIUM; CHEMOPREVENTIVE AGENTS; CAROTENOIDS; VEGETABLES; FRUIT; PREVENTION; TRIALS; MEN RP PALMER, S (reprint author), NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892, USA. NR 21 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0899-9007 J9 NUTRITION JI Nutrition PD SEP-OCT PY 1994 VL 10 IS 5 BP 433 EP 434 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA PH696 UT WOS:A1994PH69600016 ER PT J AU LANDON, MB HARGER, J MCNELLIS, D MERCER, B THOM, EA AF LANDON, MB HARGER, J MCNELLIS, D MERCER, B THOM, EA TI PREVENTION OF NEONATAL GROUP-B STREPTOCOCCAL INFECTION SO OBSTETRICS AND GYNECOLOGY LA English DT Article AB The optimal clinical strategy to prevent neonatal group B streptococcal infection has not been established. The Maternal-Fetal Medicine Units Network assessed the feasibility of a randomized clinical trial to compare the effectiveness of two methods of prevention of streptococcal infection. The attack rates of early-onset group B streptococcal disease were estimated for the following: 1) a hypothetical program of universal prenatal screening and selective intrapartum chemoprophylaxis, and 2) a hypothetical program of selective intrapartum chemoprophylaxis based on clinical risk factors. Sample size requirements were calculated for a clinical trial to detect a significant difference in attack rates between the two hypothetical programs. Similar low attack rates using both strategies would require extremely large sample sizes to detect differences between programs. Until a satisfactory, rapid diagnostic test for intrapartum group B streptococcal carrier status is developed and clinical strategies are tested in populations with varying carriage frequencies, institutions will need to individualize their approaches to prevent early-onset neonatal group B streptococcal disease. C1 NICHHD,MATERNAL FETAL MED UNITS NETWORK,BETHESDA,MD 20892. OHIO STATE UNIV,MAGEE WOMENS HOSP,COLL MED,COLUMBUS,OH. UNIV PITTSBURGH,PITTSBURGH,PA 15260. UNIV TENNESSEE,SCH MED,KNOXVILLE,TN 37996. GEORGE WASHINGTON UNIV,CTR BIOSTAT,WASHINGTON,DC 20052. UNIV ALABAMA,SCH MED,TUSCALOOSA,AL 35487. WAYNE STATE UNIV,SCH MED,DETROIT,MI 48202. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. UNIV CINCINNATI,SCH MED,CINCINNATI,OH. UNIV CHICAGO,SCH MED,CHICAGO,IL 60637. UNIV SO CALIF,SCH MED,LOS ANGELES,CA 90089. UNIV OKLAHOMA,SCH MED,NORMAN,OK 73019. MED UNIV S CAROLINA,CHARLESTON,SC 29425. NR 8 TC 24 Z9 24 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD SEP PY 1994 VL 84 IS 3 BP 460 EP 462 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA PC430 UT WOS:A1994PC43000029 PM 8058249 ER PT J AU GOLDSPIEL, BR KOHLER, DR AF GOLDSPIEL, BR KOHLER, DR TI ONDANSETRON AND METOCLOPRAMIDE FAIL TO PREVENT VOMITING SECONDARY TO ULTRA-HIGH-DOSE CISPLATIN-CARBOPLATIN CHEMOTHERAPY SO OBSTETRICS AND GYNECOLOGY LA English DT Letter RP GOLDSPIEL, BR (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT PHARM,BLDG 10,ROOM 1N-257,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD SEP PY 1994 VL 84 IS 3 BP 483 EP 483 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA PC430 UT WOS:A1994PC43000037 PM 8058256 ER PT J AU SHIMIZU, E COXON, A OTTERSON, GA STEINBERG, SM KRATZKE, RA KIM, YW FEDORKO, J OIE, H JOHNSON, BE MULSHINE, JL MINNA, JD GAZDAR, AF KAYE, FJ AF SHIMIZU, E COXON, A OTTERSON, GA STEINBERG, SM KRATZKE, RA KIM, YW FEDORKO, J OIE, H JOHNSON, BE MULSHINE, JL MINNA, JD GAZDAR, AF KAYE, FJ TI RB PROTEIN STATUS AND CLINICAL CORRELATION FROM 171 CELL-LINES REPRESENTING LUNG-CANCER, EXTRAPULMONARY SMALL-CELL CARCINOMA, AND MESOTHELIOMA SO ONCOGENE LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; ALTERED EXPRESSION; SUSCEPTIBILITY GENE; COLORIMETRIC ASSAY; BLADDER-CANCER; PHOSPHORYLATION; CYCLE; ABNORMALITIES; GROWTH; DNA AB We have studied RB protein expression in 171 cell lines derived from patients with small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), pulmonary carcinoid, mesothelioma, and extrapulmonary small cell cancer (EPSC) and have correlated this data with clinical outcome. We detected absent or aberrant RB protein expression in 66/75 SCLC, 12/80 NSCLC, 1/6 carcinoid, 0/5 mesothelioma, and 4/5 EPSC samples. In addition, we observed integration of human papilloma virus (HPV) DNA in the single EPSC cell line that retained wildtype RB protein. We did not detect integration of HPV, SV40 or adenoviral DNA in other tumor samples with wildtype RB status. We also noted a stable, hypophosphorylated mutant RB in 12 SCLC and 3 NSCLC samples which might have been falsely interpreted as wildtype by current immunohistochemical techniques. Analysis of the matched clinical data showed no associations between RB status and age, sex, extent of disease, performance status, smoking history, and previous treatment. In addition, retrospective analyses showed no consistent correlation of RB protein expression with either best clinical response, overall survival, or in vitro chemotherapeutic drug sensitivity. The stable expression of RB after gene transfection into RB(-) SCLC cells, however, resulted in a trend toward increased in vitro resistance to etoposide, cisplatin and doxorubicin. C1 NCI,NAVY ONCOL BRANCH,BETHESDA,MD 20889. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20889. NCI,BIOSTAT SECT,BETHESDA,MD 20889. DIV CANC PREVENT & CONTROL,BIOMARKERS SECT,GAITHERSBURG,MD 20850. UNIV TEXAS,SW MED CTR,SIMMONS CANC CTR,DALLAS,TX 75235. RI kaye, frederic/E-2437-2011 NR 47 TC 121 Z9 122 U1 1 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP PY 1994 VL 9 IS 9 BP 2441 EP 2448 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA PC054 UT WOS:A1994PC05400002 PM 8058306 ER PT J AU WIEST, JS BURNETT, VL ANDERSON, MW REYNOLDS, SH AF WIEST, JS BURNETT, VL ANDERSON, MW REYNOLDS, SH TI A NOVEL MECHANISM OF IN-VIVO RAS GENE ACTIVATION INVOLVING TANDEM DUPLICATION OF CODING SEQUENCES SO ONCOGENE LA English DT Article ID MURINE SARCOMA-VIRUS; P21 TRANSFORMING PROTEIN; POINT MUTATION; GTP HYDROLYSIS; HAMSTER-CELLS; APRT LOCUS; K-RAS; ONCOGENE; MOUSE; DNA AB A series of weakly transforming c-K-ras genes have been detected in spontaneously occurring and chemically induced mouse adenomas. DNA sequence analysis of these weakly transforming ras oncogenes showed that activation occurred by a novel mechanism involving duplication of nine or ten codon segments flanking codon 61 in exon 2. The codon repetitions in exon 2 are directly preceded by a number of potentially recombinogenic DNA sequences which may have been involved in the genesis of the codon repetitions through mechanisms involving recombination or DNA slippage. Duplication of DNA sequences such as those observed in the mouse c-K-ras gene may represent a new mechanism for both tumor suppressor gene inactivation and proto-oncogene activation. C1 NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709. RP WIEST, JS (reprint author), NIEHS,MOLEC TOXICOL LAB,RES TRIANGLE PK,NC 27709, USA. NR 39 TC 6 Z9 6 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP PY 1994 VL 9 IS 9 BP 2449 EP 2454 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA PC054 UT WOS:A1994PC05400003 PM 8058307 ER PT J AU HIGINBOTHAM, KG RICE, JM BUZARD, GS PERANTONI, AO AF HIGINBOTHAM, KG RICE, JM BUZARD, GS PERANTONI, AO TI ACTIVATION OF THE K-RAS GENE BY INSERTION MUTATIONS IN CHEMICALLY-INDUCED RAT RENAL MESENCHYMAL TUMORS SO ONCOGENE LA English DT Article ID HA-RAS; POINT MUTATIONS; ONCOGENE; CARCINOGENESIS; PROGRESSION; CARCINOMAS; INITIATION; AMPLIFICATION; MECHANISMS; METHYLUREA AB Previously we reported the detection of transforming K-ras sequences in methyl(methoxymethyl)nitrosamine (DMN-OMe)-induced rat renal mesenchymal tumors by NIH3T3 transfection assays. Subsequent analysis by selective oligonucleotide hybridization revealed a variety of activating point mutations in codon 12 of K-ras in most of these tumors and in their NIH3T3 transformants, but in some, point mutations could not be detected by this technique. In the current study, insertion mutations were detected in two DMN-OMe-induced tumors from this group with previously undefined transforming K-ras alterations. These primary tumors and their NIH3T3 transformants contained K-ras sequences with either a 9 bp or a 12 bp repeat in exon one, both of which included codon 12. No other mutations in the entire coding region of the K-ras gene were observed. Site-directed mutagenesis studies by others have determined that deletions and insertions near codon 12 can activate the ras gene, but this is the first demonstration of insertional activation of K-ras in a chemically induced rat tumor. C1 NCI,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. PRI DYNCORP,BCDP,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-7412] NR 30 TC 18 Z9 19 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP PY 1994 VL 9 IS 9 BP 2455 EP 2459 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA PC054 UT WOS:A1994PC05400004 PM 8058308 ER PT J AU MUSHINSKI, JF GOODNIGHT, J RUDIKOFF, E MORSE, HC LANGDON, WY AF MUSHINSKI, JF GOODNIGHT, J RUDIKOFF, E MORSE, HC LANGDON, WY TI EXPRESSION OF C-CBL PROTOONCOGENE IS MODULATED DURING DIFFERENTIATION BUT NOT DURING INDUCTION OF PROLIFERATION SO ONCOGENE LA English DT Article ID MURINE IMMUNE-SYSTEM; NF-KAPPA-B; V-CBL; POLYCLONAL ACTIVATION; TRANSCRIPTION FACTOR; DNA-BINDING; ZINC FINGER; CELLS; IDENTIFICATION; TRUNCATION AB The proto-oncogene c-cbl is expressed as two mRNAs, ca. 10.5 and 3.1 kb, both of which appear to be functional inasmuch as both can be found on polyribosomes in tissues that express both mRNAs. The function of the 120 kDa c-cbl protein is not known, but its primary structure resembles that of a DNA-binding transcription factor with a basic region, a nuclear localization sequence, a zinc finger-like motif and a leucine zipper. To test whether expression of this protein resembles that of regulatory proteins, we studied expression of c-cbl mRNA and protein in differentiating cells and in proliferating cells, conditions in which expression of regulatory proteins commonly is modulated. Differentiation of both erythroleukemia cells and teratocarcinoma cells showed a decrease in c-cbl expression, with kinetics similar to those of transcription factors that are immediate early response genes. Unlike early response genes, however, c-cbl mRNA showed a very long half life in B lymphocytes. Further, in fibroblasts and spleen cells that were induced to proliferate, c-cbl mRNA expression did not change, and expression of c-cbl protein did not change during any stage of the cell cycle. These characteristics indicate that c-cbl does not belong to the immediate early response type of transcription factor. Yet when c-cbl is truncated, as in v-cbl, the protein does enter the nucleus and bind DNA, and it contributes to neoplastic transformation of B lymphocytes and fibroblasts. These findings indicate that the regulation of the c-cbl proto-oncogene is different from that of the proto-oncogenes identified to date and suggest that c-cbl belongs to a new class of proto-oncogenes. C1 NIAID,IMMUNOPATHOL LAB,BETHESDA,MD 20892. UNIV WESTERN AUSTRALIA,DEPT BIOCHEM,NEDLANDS,WA 6009,AUSTRALIA. RP MUSHINSKI, JF (reprint author), NCI,MOLEC GENET SECT,BETHESDA,MD 20892, USA. OI Morse, Herbert/0000-0002-9331-3705 NR 30 TC 20 Z9 20 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP PY 1994 VL 9 IS 9 BP 2489 EP 2497 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA PC054 UT WOS:A1994PC05400008 PM 8058312 ER PT J AU WANG, HG MIYASHITA, T TAKAYAMA, S SATO, T TORIGOE, T KRAJEWSKI, S TANAKA, S HOVEY, L TROPPMAIR, J RAPP, UR REED, JC AF WANG, HG MIYASHITA, T TAKAYAMA, S SATO, T TORIGOE, T KRAJEWSKI, S TANAKA, S HOVEY, L TROPPMAIR, J RAPP, UR REED, JC TI APOPTOSIS REGULATION BY INTERACTION OF BCL-2 PROTEIN AND RAF-1 KINASE SO ONCOGENE LA English DT Note ID EPSTEIN-BARR-VIRUS; CELL-DEATH; PROTOONCOGENE EXPRESSION; RAS; ONCOPROTEIN; ACTIVATION; LINE; PHOSPHORYLATION; ONCOGENES; PROSTATE AB The Bcl-2 protein is over-produced in many types of human tumors and suppresses apoptosis induced by a wide-variety of stimuli, including chemotherapeutic drugs and gamma-irradiation. The biochemical mechanism of action of the Bcl-2 protein however remains enigmatic. Here we show that Bcl-2 can be co-immunoprecipitated with the serine/ threonine-specific Raf-1 kinase both in a mammalian hemopoietic cell 32D.3 and when the two proteins are produced in Sf9 insect cells using recombinant baculoviruses. Though analysis of-Raf-1 deletion mutants suggested that the C-terminal half of the protein which contains the catalytic domain is sufficient for co-immunoprecipitation with Bcl-2, Raf-1 does not appear to induce phosphorylation of Bcl-2 protein in 32D.3 and Sf9 cells. Furthermore, a mutant form of Raf-1 that lacks kinase activity could still be co-immunoprecipitated with Bcl-2 in Sf9 cells, suggesting that the interaction of these proteins does not reflect a kinase-substrate relation, Gene transfer experiments using 32D.3 hemopoietic cells demonstrated functional synergy between Bcl-2 and Raf-1 with regards to suppression of apoptosis induced by growth factor withdrawal. Taken together, these observations for the first time functionally link Bcl-2 to a signal transducing protein and suggest that the interaction of the Bcl-2 and Raf-1 proteins may be responsible for their ability to cooperate in the suppression of apoptosis. C1 LA JOLLA CANC RES FDN,CANC RES CTR,LA JOLLA,CA 92037. NCI,FREDERICK CANC RES FACIL,TUMOR VIROL LAB,FREDERICK,MD 21702. RI Wang, Hong-Gang/A-3018-2015 FU NCI NIH HHS [CA-54957] NR 47 TC 230 Z9 237 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP PY 1994 VL 9 IS 9 BP 2751 EP 2756 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA PC054 UT WOS:A1994PC05400040 PM 8058342 ER PT J AU PETERS, AC SMYTHE, AM WU, L MONKS, A BOYD, MR SHOEMAKER, RH AF PETERS, AC SMYTHE, AM WU, L MONKS, A BOYD, MR SHOEMAKER, RH TI LEVELS OF MESSENGER-RNA CODING FOR DNA TOPOISOMERASE-II ISOFORMS DO NOT CORRELATE WITH IN-VITRO DRUG-SENSITIVITY SO ONCOLOGY REPORTS LA English DT Article DE TOPOISOMERASE II; DRUG SENSITIVITY; PCR ID POLYMERASE CHAIN-REACTION; TUMOR-CELL-LINES; MESSENGER-RNA; MULTIDRUG RESISTANCE; GENE-EXPRESSION; QUANTITATION; OVEREXPRESSION; CLONING; SCREEN AB The relationship between cellular levels of mRNA coding for DNA topoisomerase II, both the alpha and beta isoforms, and in vitro sensitivity to anticancer drugs were evaluated. Using a sensitive RNA-polymerase chain reaction technique, the levels of mRNA coding for the alpha and beta isoforms of topoisomerase II were estimated relative to beta-actin mRNA. A relatively narrow range of expression was observed across a broad range of approximately 60 human tumor cell lines representing eight major histological types which have been characterized in detail with respect to their in vitro sensitivity to standard anticancer drugs. No significant correlations were observed between mRNA level and cellular response to drugs thought to inhibit topoisomerase II or any of the other drugs studied. These results suggest that predictive tests for response to topoisomerase II-related drugs can not be based on estimation of levels of mRNA. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702. NR 18 TC 3 Z9 3 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD SEP-OCT PY 1994 VL 1 IS 5 BP 907 EP 911 PG 5 WC Oncology SC Oncology GA PW228 UT WOS:A1994PW22800009 PM 21607464 ER PT J AU GOLDSTEIN, AM BLOT, WJ GREENBERG, RS SCHOENBERG, JB AUSTIN, DF PRESTONMARTIN, S WINN, DM BERNSTEIN, L MCLAUGHLIN, JK FRAUMENI, JF AF GOLDSTEIN, AM BLOT, WJ GREENBERG, RS SCHOENBERG, JB AUSTIN, DF PRESTONMARTIN, S WINN, DM BERNSTEIN, L MCLAUGHLIN, JK FRAUMENI, JF TI FAMILIAL RISK IN ORAL AND PHARYNGEAL CANCER SO ORAL ONCOLOGY-EUROPEAN JOURNAL OF CANCER PART B LA English DT Article ID NECK-CANCER; HUMAN HEAD; P53 GENE; CARCINOMAS; MUTATIONS; SENSITIVITY; DELETIONS; DRINKING; SMOKING AB We examined the relationship between a family history of cancer and risk of oral and pharyngeal cancer using epidemiological data from a large case-control investigation of these tumours. 487 (45.7%) of the cases and 485 (41.0%) of the controls reported cancer in a parent or a sibling. After controlling for age, race, sex, study location, respondent status and smoking and alcohol use, the OR associated with any cancer in the family was 1.1 [95% confidence interval (CI) 0.9-1.3]. Risks were nonsignificantly elevated among those with a history of cancers arising from the oral cavity/pharynx (OR=1.2, 95% CI 0.7-2.3), oesophagus/larynx (OR=1.6, 95% CI-0.7-3.8) and lung (OR=1.2, 95% CI 0.8-1.8), with the excess risk primarily among those for whom a male relative, particularly a brother, was affected with these smoking-related cancers. In addition, an elevated risk of oral/pharynx cancer was found among those whose sisters developed other cancers (OR=1.6; 95% CI 1.1-2.2). Subsite analyses revealed stronger elevated risks of smoking-related cancers in relatives of pharyngeal cancer cases (OR=1.7, 95% CI 1.1-2.8) than of oral cancer patients. The data indicate that there is at most a weak familial aggregation of oral/pharynx cancers. Furthermore, since the excess familial risk of oral/pharynx cancer was associated with smoking-related cancers among male but not female relatives, it seems likely that environmental factors (notably smoking and drinking) contribute to the familial tendency observed in this study. The results underscore the need to collect risk profile information on relatives in future studies to disentangle genetic from environmental determinants. C1 EMORY UNIV,ATLANTA,GA 30322. NEW JERSEY DEPT HLTH,TRENTON,NJ 08625. CALIF DEPT HLTH SERV,EMERYVILLE,CA 94608. UNIV SO CALIF,LOS ANGELES,CA 90033. NATL CTR HLTH STAT,HYATTSVILLE,MD 20782. RP GOLDSTEIN, AM (reprint author), NCI,BETHESDA,MD 20892, USA. NR 20 TC 36 Z9 36 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0964-1955 J9 ORAL ONCOL JI Oral Oncol.-Eur. J. Cancer Pt. B PD SEP PY 1994 VL 30B IS 5 BP 319 EP 322 PG 4 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA PM215 UT WOS:A1994PM21500007 ER PT J AU HAUPT, R FEARS, TR ROSSO, P COLELLA, R LOIACONO, G DETERLIZZI, M MANCINI, A COMELLI, A INDOLFI, P DONFRANCESCO, A OPERAMOLLA, P GRAZIA, G CECI, A TUCKER, MA AF HAUPT, R FEARS, TR ROSSO, P COLELLA, R LOIACONO, G DETERLIZZI, M MANCINI, A COMELLI, A INDOLFI, P DONFRANCESCO, A OPERAMOLLA, P GRAZIA, G CECI, A TUCKER, MA TI INCREASED RISK OF SECONDARY LEUKEMIA AFTER SINGLE-AGENT TREATMENT WITH ETOPOSIDE FOR LANGERHANS CELL HISTIOCYTOSIS SO PEDIATRIC HEMATOLOGY AND ONCOLOGY LA English DT Article DE ETOPOSIDE; LANGERHANS CELL HISTIOCYTOSIS; LATE EFFECTS; SECONDARY LEUKEMIA ID ACUTE MYELOID-LEUKEMIA; ACUTE NONLYMPHOCYTIC LEUKEMIA; MYELODYSPLASTIC SYNDROME; CHEMOTHERAPY; EPIPODOPHYLLOTOXINS; THERAPY; ASSOCIATION; CISPLATIN; CHILDHOOD; CANCER AB The study evaluated 139 patients diagnosed with Langerhans' cell histiocytosis (LCH) and enrolled in any protocol of the Italian Association of Pediatric Hematology/Oncology since 1982. Treatment was etoposide (VP-16) only in 50 patients, VP-16 and other drugs with an already established leukemogenic effect in 17 patients, only drugs with leukemogenic effect in 6 patients, other drugs in 35 patients, and surgery only in 31 patients. Median length of follow-up after diagnosis was 65 months (range, 1 to 126 months) for a total of 742.5 person-years at risk (PYRs). Three cases of acute myelogenous leukemia (AML) were reported; only 0.0044 case was expected. The standard incidence ratio (SIR) of AML in this cohort was 680.5 [95% confidence interval (CI), 140.2-1988.5], and the incidence rate per 1000 PYRs was 4.0 (95% CI, 0.8-11.8). For the subgroup treated with single-agent VP-16, the SIR after treatment was 2270.0 (95% CI, 275-8199), and the incidence rate after treatment was 14.7 (95% CI, 1.8-42.8). The study confirms a higher risk of leukemia after LCH and supports the hypothesis of an association between treatment-related acute nonlymphocytic leukemia and single-agent treatment with VP-16. C1 GIANNINA GASLINI CHILDRENS HOSP,DIV PEDIAT HEMATOL ONCOL,GENOA,ITALY. NCI,DIV CANC ETIOL,BETHESDA,MD 20892. UNIV TURIN,DEPT PEDIAT,I-10124 TURIN,ITALY. UNIV BARI,DEPT PEDIAT,I-70124 BARI,ITALY. UNIV BOLOGNA,DEPT PEDIAT,I-40126 BOLOGNA,ITALY. UNIV NAPLES,DEPT PEDIAT,I-80138 NAPLES,ITALY. BAMBIN GESU HOSP,DEPT PEDIAT HEMATOL ONCOL,ROME,ITALY. UNIV ROME,DEPT PEDIAT 2,I-00100 ROME,ITALY. RI Haupt, Riccardo/C-2237-2012; Tucker, Margaret/B-4297-2015 NR 23 TC 21 Z9 22 U1 0 U2 0 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0888-0018 J9 PEDIATR HEMAT ONCOL JI Pediatr. Hematol. Oncol. PD SEP-OCT PY 1994 VL 11 IS 5 BP 499 EP 507 PG 9 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA PG988 UT WOS:A1994PG98800005 PM 7826846 ER PT J AU HALL, CB CHESNEY, PJ GROMISCH, DS HALSEY, NA KOHL, S MARCY, SM MARKS, MI NANKERVIS, GA OVERALL, JC PICKERING, LK STEELE, RW YOGEV, R PETER, G BERKELMAN, RL HARDEGREE, MC JACOBS, RF MACDONALD, NE ORENSTEIN, WA RABINOVICH, NR ROBBINS, A AF HALL, CB CHESNEY, PJ GROMISCH, DS HALSEY, NA KOHL, S MARCY, SM MARKS, MI NANKERVIS, GA OVERALL, JC PICKERING, LK STEELE, RW YOGEV, R PETER, G BERKELMAN, RL HARDEGREE, MC JACOBS, RF MACDONALD, NE ORENSTEIN, WA RABINOVICH, NR ROBBINS, A TI UPDATE ON TIMING OF HEPATITIS-B VACCINATION FOR PREMATURE-INFANTS AND FOR CHILDREN WITH LAPSED IMMUNIZATION - COMMITTEE ON INFECTIOUS-DISEASES SO PEDIATRICS LA English DT Editorial Material C1 CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. US FDA,ROCKVILLE,MD 20857. CANADIAN PAEDIAT SOC,OTTAWA,ON,CANADA. NIH,BETHESDA,MD 20892. NATL VACCINE PROGRAM,ROCKVILLE,MD. NR 11 TC 16 Z9 16 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 1994 VL 94 IS 3 BP 403 EP 404 PG 2 WC Pediatrics SC Pediatrics GA PE782 UT WOS:A1994PE78200024 ER PT J AU SCHINDLER, CW PERSICO, AM UHL, GR GOLDBERG, SR AF SCHINDLER, CW PERSICO, AM UHL, GR GOLDBERG, SR TI BEHAVIORAL-ASSESSMENT OF HIGH-DOSE AMPHETAMINE WITHDRAWAL - IMPORTANCE OF TRAINING AND TESTING CONDITIONS SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE AMPHETAMINE; WITHDRAWAL; LOCOMOTOR ACTIVITY; SWIM TEST; RATS ID DEPRESSION; EXPRESSION; RATS AB Chronic d-amphetamine-treated rats were given twice daily injections at a dose of 7.5 mg/kg for 2 weeks. Acute amphetamine and saline groups of rats were given saline treatments during this time, except that for the acute group the final injection was 7.5 mg/kg d-amphetamine. Acute and chronic amphetamine groups habituated to the locomotor activity testing apparatus showed increases in both distance traveled and repetitive movement time that lasted up to 6 h following the final injection. When animals were not habituated to the activity test apparatus, however, a significant decrease in repetitive movement time was noted for the chronic amphetamine group 24-54 h following the final amphetamine injection; no differences were observed for distance traveled when the locomotor activity apparatus was novel. Swim test immobility time was assessed twice following the last injection, with the second test following the first,by approximately 24 h. During the first test, decreases in immobility were observed for both chronic and acute amphetamine groups, 6-12 h following the last injection. However, during the second test, decreases in immobility time were observed only for the chronic amphetamine groups 36-72 h following the final injection. These results indicate that 24 to 72 h after the end of the chronic amphetamine regimen a withdrawal effect was observed for both repetitive movement time in the locomotor activity test and immobility time in the swim test. The withdrawal effect was observed only for the locomotor activity groups for whom the test apparatus was novel, and only during the second test of immobility time for the swim test groups. Thus, the method of behavioral assessment can be critical for the demonstration of a high-dose amphetamine withdrawal effect. C1 NIDA,ADDICT RES CTR,MOLEC NEUROBIOL BRANCH,BALTIMORE,MD 21224. RP SCHINDLER, CW (reprint author), NIDA,ADDICT RES CTR,PRECLIN PHARMACOL BRANCH,BEHAV PHARMACOL & GENET SECT,POB 5180,BALTIMORE,MD 21224, USA. NR 20 TC 17 Z9 17 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD SEP PY 1994 VL 49 IS 1 BP 41 EP 46 DI 10.1016/0091-3057(94)90454-5 PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA PE776 UT WOS:A1994PE77600007 PM 7816888 ER PT J AU LARRALDE, H WEISS, GH STANLEY, HE AF LARRALDE, H WEISS, GH STANLEY, HE TI THE EXPECTED NUMBER OF DISTINCT SITES VISITED BY N-BIASED RANDOM-WALKS IN ONE-DIMENSION SO PHYSICA A-STATISTICAL MECHANICS AND ITS APPLICATIONS LA English DT Article AB We calculate the asymptotic form of the expected number of distinct sites visited by N random walkers moving independently in one dimension. It is shown that to lowest order and at long times, the leading term in the asymptotic result is that found for the random walk of a single biased particle, which implies that the bias is strong enough a factor to dominate the many-body effects in that regime. The lowest order correction term contains the many-body contribution. This is essentially the result for the unbiased random walk. C1 BOSTON UNIV, DEPT PHYS, BOSTON, MA 02215 USA. NIH, DIV COMP RES & TECHNOL, PHYS SCI LAB, BETHESDA, MD 20892 USA. NR 11 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 EI 1873-2119 J9 PHYSICA A JI Physica A PD SEP 1 PY 1994 VL 209 IS 3-4 BP 361 EP 368 DI 10.1016/0378-4371(94)90189-9 PG 8 WC Physics, Multidisciplinary SC Physics GA PF970 UT WOS:A1994PF97000007 ER PT J AU TAITELBAUM, H WEISS, GH AF TAITELBAUM, H WEISS, GH TI ANOMALOUS SEGREGATION AT A SINGLE TRAP IN DISORDERED CHAINS SO PHYSICAL REVIEW E LA English DT Note ID NEAREST-NEIGHBOR DISTANCES; DIFFUSION-CONTROLLED REACTIONS; ULTRATHIN MOLECULAR WIRES; STATISTICAL PROPERTIES; IMPERFECT TRAP; 2 DIMENSIONS; MOBILE TRAP; RANDOM-WALK; MODEL; PARTICLES AB We study the repulsion of Brownian particles induced by a single trap on disordered chains. Two different types of disorder are considered: random local bias fields (the Sinai model) and random transition rates. We discuss two possible measures of segregation for each system, and show that they can have either similar or different universal behavior, depending on the properties of diffusion subject to the hard-core potential in each system. We also report on anomalous scaling properties for the average trapping rate and the average density profile of the diffusing particles. It is surprisingly shown that the latter is not spatially linear in the vicinity of the trap, but rather has a hat tail in the case of random fields, and a nonuniversal power law in the case of random transition rates. C1 NIH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20892. RP TAITELBAUM, H (reprint author), BAR ILAN UNIV,DEPT PHYS,IL-52900 RAMAT GAN,ISRAEL. NR 33 TC 10 Z9 10 U1 0 U2 0 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1063-651X J9 PHYS REV E JI Phys. Rev. E PD SEP PY 1994 VL 50 IS 3 BP 2357 EP 2360 DI 10.1103/PhysRevE.50.2357 PG 4 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA PJ443 UT WOS:A1994PJ44300078 ER PT J AU HARLAN, WR KALBERER, JT VOGEL, MA AF HARLAN, WR KALBERER, JT VOGEL, MA TI DISEASE PREVENTION RESEARCH AT NIH - AN AGENDA FOR ALL - INTRODUCTION SO PREVENTIVE MEDICINE LA English DT Editorial Material RP HARLAN, WR (reprint author), NIH,OFF DIRECTOR,OFF DIS PREVENT,BETHESDA,MD 20892, USA. NR 1 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD SEP PY 1994 VL 23 IS 5 BP 547 EP 548 DI 10.1006/pmed.1994.1077 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA PR128 UT WOS:A1994PR12800001 PM 7845904 ER PT J AU WYNDER, EL ANDRES, R AF WYNDER, EL ANDRES, R TI WORKSHOP-A - DIET AND NUTRITION RESEARCH AS IT RELATES TO AGING AND CHRONIC DISEASES SO PREVENTIVE MEDICINE LA English DT Article; Proceedings Paper CT Seminal Conference on Disease Prevention Research at NIH: An Agenda for All CY OCT 06-08, 1993 CL BETHESDA, MD SP NIH C1 NIA,BETHESDA,MD 20892. RP WYNDER, EL (reprint author), AMER HLTH FDN,NEW YORK,NY 10017, USA. NR 0 TC 3 Z9 4 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD SEP PY 1994 VL 23 IS 5 BP 549 EP 551 DI 10.1006/pmed.1994.1078 PG 3 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA PR128 UT WOS:A1994PR12800002 PM 7845905 ER PT J AU BLENDON, RJ HEIMENDINGER, J MARWIDK, CS AF BLENDON, RJ HEIMENDINGER, J MARWIDK, CS TI WORKSHOP-D - NIH INTERFACE WITH PUBLIC TRANSLATION AND POLICY SO PREVENTIVE MEDICINE LA English DT Article; Proceedings Paper CT Seminal Conference on Disease Prevention Research at NIH: An Agenda for All CY OCT 06-08, 1993 CL BETHESDA, MD SP NIH C1 NCI,BETHESDA,MD 20892. RP BLENDON, RJ (reprint author), HARVARD UNIV,SCH PUBL HLTH,CAMBRIDGE,MA 02138, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD SEP PY 1994 VL 23 IS 5 BP 556 EP 557 DI 10.1006/pmed.1994.1081 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA PR128 UT WOS:A1994PR12800005 PM 7845908 ER PT J AU GAVIN, JR GIFT, HC AF GAVIN, JR GIFT, HC TI WORKSHOP-G - INVOLVEMENT OF THE PRIVATE-SECTOR IN PREVENTION RESEARCH SO PREVENTIVE MEDICINE LA English DT Article; Proceedings Paper CT Seminal Conference on Disease Prevention Research at NIH: An Agenda for All CY OCT 06-08, 1993 CL BETHESDA, MD SP NIH C1 NIDR,BETHESDA,MD 20892. RP GAVIN, JR (reprint author), HOWARD HUGHES MED INST,COCONUT GROVE,FL 33133, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD SEP PY 1994 VL 23 IS 5 BP 563 EP 565 DI 10.1006/pmed.1994.1084 PG 3 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA PR128 UT WOS:A1994PR12800008 PM 7845911 ER PT J AU KALBERER, JT PARKINSON, MD AF KALBERER, JT PARKINSON, MD TI WORKSHOP-H - INVOLVEMENT OF OTHER PHS AGENCIES AND PROFESSIONAL SOCIETIES IN PREVENTION RESEARCH SO PREVENTIVE MEDICINE LA English DT Article; Proceedings Paper CT Seminal Conference on Disease Prevention Research at NIH: An Agenda for All CY OCT 06-08, 1993 CL BETHESDA, MD SP NIH C1 USAF,OFF SURGEON GEN,WASHINGTON,DC 20330. RP KALBERER, JT (reprint author), NIMH,OFF DIRECTOR,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD SEP PY 1994 VL 23 IS 5 BP 566 EP 568 DI 10.1006/pmed.1994.1085 PG 3 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA PR128 UT WOS:A1994PR12800009 PM 7845912 ER PT J AU KALBERER, JT VOGEL, MA HARLAN, WR AF KALBERER, JT VOGEL, MA HARLAN, WR TI SUMMARY OF WORKSHOP RECOMMENDATIONS SO PREVENTIVE MEDICINE LA English DT Editorial Material C1 NIH,OFF DIS PREVENT,BETHESDA,MD 20892. RP KALBERER, JT (reprint author), NIH,OFF DIRECTOR,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD SEP PY 1994 VL 23 IS 5 BP 573 EP 577 DI 10.1006/pmed.1994.1088 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA PR128 UT WOS:A1994PR12800012 PM 7845915 ER PT J AU KIRCHSTEIN, RL AF KIRCHSTEIN, RL TI WELCOMING REMARKS - THE ROLE OF THE NIH IN THE NATIONAL PREVENTION INITIATIVE SO PREVENTIVE MEDICINE LA English DT Editorial Material RP KIRCHSTEIN, RL (reprint author), NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD SEP PY 1994 VL 23 IS 5 BP 578 EP 579 DI 10.1006/pmed.1994.1089 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA PR128 UT WOS:A1994PR12800013 ER PT J AU HARLAN, WR AF HARLAN, WR TI FUTURE PARADIGMS FOR PREVENTION RESEARCH SO PREVENTIVE MEDICINE LA English DT Article; Proceedings Paper CT Seminal Conference on Disease Prevention Research at NIH: An Agenda for All CY OCT 06-08, 1993 CL BETHESDA, MD SP NIH RP HARLAN, WR (reprint author), NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD SEP PY 1994 VL 23 IS 5 BP 583 EP 583 DI 10.1006/pmed.1994.1091 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA PR128 UT WOS:A1994PR12800015 PM 7845917 ER PT J AU GOTTESMAN, MM COLLINS, FS AF GOTTESMAN, MM COLLINS, FS TI THE ROLE OF THE HUMAN GENOME PROJECT IN DISEASE PREVENTION SO PREVENTIVE MEDICINE LA English DT Article; Proceedings Paper CT Seminal Conference on Disease Prevention Research at NIH: An Agenda for All CY OCT 06-08, 1993 CL BETHESDA, MD SP NIH ID CLONING AB The Human Genome Project has made it easier to genetically map and clone mutant genes which predispose to a great many human diseases. In addition to diseases inherited in a simple Mendelian fashion, there are many degenerative and infectious diseases, and sensitivities to environmental insults, in which the genetic make-up of an individual contributes to the course of the disease. Once a gene or genes associated with disease has been cloned, it is possible to design DNA-based diagnostics to detect altered forms of the gene which predispose to disease. The ability to predict the development of disease makes possible early intervention to limit the severity of a disease or to use gene therapy to cure inherited disorders. C1 NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP GOTTESMAN, MM (reprint author), NCI,CELL BIOL LAB,BLDG 37,ROOM 1B22,BETHESDA,MD 20892, USA. NR 4 TC 8 Z9 9 U1 1 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD SEP PY 1994 VL 23 IS 5 BP 591 EP 594 DI 10.1006/pmed.1994.1094 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA PR128 UT WOS:A1994PR12800018 PM 7845920 ER PT J AU GOODWIN, FK AF GOODWIN, FK TI MATERNAL AND CHILD HEALTH - OVERVIEW SO PREVENTIVE MEDICINE LA English DT Article; Proceedings Paper CT Seminal Conference on Disease Prevention Research at NIH: An Agenda for All CY OCT 06-08, 1993 CL BETHESDA, MD SP NIH RP GOODWIN, FK (reprint author), NIMH,ROOM 17-99,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD SEP PY 1994 VL 23 IS 5 BP 622 EP 623 DI 10.1006/pmed.1994.1101 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA PR128 UT WOS:A1994PR12800025 PM 7845926 ER PT J AU ROSENBERG, SA AF ROSENBERG, SA TI THE GENE-THERAPY OF CANCER SO PREVENTIVE MEDICINE LA English DT Article; Proceedings Paper CT Seminal Conference on Disease Prevention Research at NIH: An Agenda for All CY OCT 06-08, 1993 CL BETHESDA, MD SP NIH ID TUMOR-INFILTRATING LYMPHOCYTES; ESTABLISHED PULMONARY METASTASES; HIGH-DOSE INTERLEUKIN-2; ACTIVATED KILLER CELLS; NECROSIS-FACTOR-ALPHA; RECOMBINANT INTERLEUKIN-2; ADOPTIVE IMMUNOTHERAPY; MELANOMA; HUMANS RP ROSENBERG, SA (reprint author), NCI,BETHESDA,MD 20892, USA. NR 17 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD SEP PY 1994 VL 23 IS 5 BP 624 EP 626 DI 10.1006/pmed.1994.1102 PG 3 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA PR128 UT WOS:A1994PR12800026 PM 7845927 ER PT J AU ALEXANDER, D AF ALEXANDER, D TI ADOLESCENTS AND YOUNG-ADULTS - OVERVIEW SO PREVENTIVE MEDICINE LA English DT Article; Proceedings Paper CT Seminal Conference on Disease Prevention Research at NIH: An Agenda for All CY OCT 06-08, 1993 CL BETHESDA, MD SP NIH RP ALEXANDER, D (reprint author), NICHHD,BLDG 31,ROOM 2A03,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD SEP PY 1994 VL 23 IS 5 BP 653 EP 654 DI 10.1006/pmed.1994.1108 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA PR128 UT WOS:A1994PR12800032 PM 7845933 ER PT J AU SHULMAN, LE AF SHULMAN, LE TI ADULTS - OVERVIEW SO PREVENTIVE MEDICINE LA English DT Article; Proceedings Paper CT Seminal Conference on Disease Prevention Research at NIH: An Agenda for All CY OCT 06-08, 1993 CL BETHESDA, MD SP NIH RP SHULMAN, LE (reprint author), NIAMSD,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD SEP PY 1994 VL 23 IS 5 BP 700 EP 700 DI 10.1006/pmed.1994.1117 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA PR128 UT WOS:A1994PR12800041 ER PT J AU KADOR, PF TAKAHASHI, Y SATO, S WYMAN, M AF KADOR, PF TAKAHASHI, Y SATO, S WYMAN, M TI AMELIORATION OF DIABETES-LIKE RETINAL CHANGES IN GALACTOSE-FED DOGS SO PREVENTIVE MEDICINE LA English DT Article; Proceedings Paper CT Seminal Conference on Disease Prevention Research at NIH: An Agenda for All CY OCT 06-08, 1993 CL BETHESDA, MD SP NIH ID ALDOSE REDUCTASE INHIBITOR; VASCULAR-PERMEABILITY; RETINOPATHY; RATS; INCREASES; CATARACT AB Diabetic retinopathy, the leading cause of blindness among young adults in the developed world, is characterized by vascular changes of the retinal capillary bed. Beagles fed a diet containing 30% galactose develop retinal vascular lesions that are similar to those observed in diabetics. These progress from initial retinal changes which include aldose-reductase-linked formation of pericyte ghosts and the subsequent development of acellular capillaries, microaneurysms, and intraretinal hemorrhages to the appearance of occluded vessels, areas of nonperfusion, and intraretinal microvascular abnormalities (IRMA) and in the final stages, the formation of fibrovascular membranes on both the retinal surface and the posterior hyaloid membrane. In prevention studies utilizing 0.5, 5.0, 10, and 16 mg/kg/day of the aldose reductase inhibitor M79175 (2-methyl-6-fluoro-spiro-chroman-4-5'-imidazolidine-2',4'-dione), pericyte ghost formation, and the subsequent appearance of microaneurysms, intraretinal hemorrhages, acellular capillaries associated with background retinopathy were arrested in a dose-dependent manner. Similar dose-dependent changes in the appearance of cataracts were also observed. The dog represents the first animal model to demonstrate all of the clinical and histological retinal vessel changes observed in human diabetics. RP KADOR, PF (reprint author), NEI,OCULAR THERAPEUTICS LAB,BETHESDA,MD 20892, USA. NR 27 TC 24 Z9 24 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD SEP PY 1994 VL 23 IS 5 BP 717 EP 721 DI 10.1006/pmed.1994.1122 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA PR128 UT WOS:A1994PR12800046 PM 7845946 ER PT J AU HADLEY, EC SHERMAN, SS SLATER, SL TAMBOLI, A HODES, RJ AF HADLEY, EC SHERMAN, SS SLATER, SL TAMBOLI, A HODES, RJ TI DISEASE PREVENTION FOR OLDER ADULTS - OVERVIEW SO PREVENTIVE MEDICINE LA English DT Article ID EPIDEMIOLOGY; DEPRESSION; POPULATION RP HADLEY, EC (reprint author), NIA, BLDG 31, ROOM 5C35, BETHESDA, MD 20892 USA. NR 16 TC 0 Z9 0 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 0091-7435 EI 1096-0260 J9 PREV MED JI Prev. Med. PD SEP PY 1994 VL 23 IS 5 BP 733 EP 734 DI 10.1006/pmed.1994.1125 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA PR128 UT WOS:A1994PR12800049 PM 7845949 ER PT J AU SPERDUTO, RD AF SPERDUTO, RD TI AGE-RELATED CATARACTS - SCOPE OF PROBLEM AND PROSPECTS FOR PREVENTION SO PREVENTIVE MEDICINE LA English DT Article ID POSTERIOR SUBCAPSULAR CATARACTS; BEAVER DAM EYE; CIGARETTE-SMOKING; LENS OPACITIES; ASPIRIN USE; EPIDEMIOLOGIC ASSOCIATIONS; RANDOMIZED TRIAL; MACULAR CHANGES; FRAMINGHAM EYE; RISK-FACTORS AB Cataracts develop in the lens of the eye which is responsible for focusing incoming light onto the retina. Early in life the lens is transparent, and incoming light encounters no difficulty in its passage through the eye. With aging, the lens becomes less clear, incoming light is scattered to an increasing degree, and if loss of lens clarity is severe enough, vision is affected. When clouding of the lens impairs vision, a clinically significant cataract is present. Currently there is no medical treatment for age-related cataract. The only treatment is surgical removal of the affected lens when vision is sufficiently impaired. A major goal of past and ongoing epidemiologic studies is the identification of risk factors for cataract, so that strategies for the prevention of cataract can be developed. RP NEI, DIV BIOMETRY & EPIDEMIOL, BLDG 31, ROOM 6A52, BETHESDA, MD 20892 USA. NR 48 TC 7 Z9 7 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 0091-7435 EI 1096-0260 J9 PREV MED JI Prev. Med. PD SEP PY 1994 VL 23 IS 5 BP 735 EP 739 DI 10.1006/pmed.1994.1126 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA PR128 UT WOS:A1994PR12800050 PM 7845950 ER PT J AU FERRIS, FL AF FERRIS, FL TI RESULTS OF 20 YEARS OF RESEARCH ON THE TREATMENT OF DIABETIC-RETINOPATHY SO PREVENTIVE MEDICINE LA English DT Article AB Diabetic retinopathy is the leading cause of blindness in young adults, ages 20-55. Without treatment 50% of those with proliferative diabetic retinopathy will be blind within 5 years. Over the last 2 decades the National Eye Institute has supported four different multicenter randomized clinical trials for diabetic retinopathy. Implementation of the results from these clinical trials can markedly reduce the risk of blindness. RP FERRIS, FL (reprint author), NEI, DIV BIOMETRY & EPIDEMIOL, CLIN TRIALS BRANCH, BETHESDA, MD 20892 USA. NR 14 TC 8 Z9 8 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 0091-7435 EI 1096-0260 J9 PREV MED JI Prev. Med. PD SEP PY 1994 VL 23 IS 5 BP 740 EP 742 DI 10.1006/pmed.1994.1127 PG 3 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA PR128 UT WOS:A1994PR12800051 PM 7845951 ER PT J AU KIRSCHSTEIN, RL AF KIRSCHSTEIN, RL TI DISEASE PREVENTION RESEARCH AT NIH - AN AGENDA FOR ALL - CLOSING REMARKS SO PREVENTIVE MEDICINE LA English DT Editorial Material RP KIRSCHSTEIN, RL (reprint author), NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD SEP PY 1994 VL 23 IS 5 BP 766 EP 766 DI 10.1006/pmed.1994.1132 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA PR128 UT WOS:A1994PR12800056 ER PT J AU STAHL, SJ KAUFMAN, JD VIKICTOPIC, S CROUCH, RJ WINGFIELD, PT AF STAHL, SJ KAUFMAN, JD VIKICTOPIC, S CROUCH, RJ WINGFIELD, PT TI CONSTRUCTION OF AN ENZYMATICALLY ACTIVE RIBONUCLEASE-H DOMAIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REVERSE-TRANSCRIPTASE SO PROTEIN ENGINEERING LA English DT Article DE HUMAN IMMUNODEFICIENCY VIRUS; HYBRID PROTEINS; REVERSE TRANSCRIPTASE; RNASE H ID RECOMBINANT ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; ANGSTROM RESOLUTION; DNA; PURIFICATION; SEQUENCE; MUTAGENESIS; SPECIFICITY; POLYMERASE; REMOVAL AB The isolated ribonuclease (RNase) H domain of human immunodeficiency virus type 1 (HIV-1) is enzymatically inactive. The incorporation of the putative substrate binding site of Escherichia coli RNase HI (amino acid residues 76-102, the alpha(c)-helix and adjacent loop region) into the equivalent position of the RNase H domain of HIV-1 resulted in a highly active hybrid protein dependent on Mn2+. Similar restoration of RNase II: activity has been observed when histidine residues are added to either the N- or C-terminus of the HIV-1 RNase H domain. The hybrid HIV-1/E.coli RNase H protein is similar to-10-fold more active than HIV-1 reverse transcriptase and 30-fold more active than the histidine-tagged proteins, indicating that the alpha(c)-helix and adjacent loop region of E.coli RNase HI is an excellent substrate binding region because of its sequence and/or location. The RNase H hybrid produced the same specific cleavage in the model tRNA(Lys3) primer removal assay as HIV-1 reverse transcriptase, showing that substrate binding and specificity are separable and that the specificity determinants are at least partially, if not totally, contained in the amino acid sequence of the hybrid protein derived from HIV-1 reverse transcriptase. C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. RP STAHL, SJ (reprint author), NICHHD,OFF DIRECTOR,PROT EXPRESS LAB,BETHESDA,MD 20892, USA. NR 36 TC 43 Z9 43 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD SEP PY 1994 VL 7 IS 9 BP 1103 EP 1108 DI 10.1093/protein/7.9.1103 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA PG507 UT WOS:A1994PG50700007 PM 7530360 ER PT J AU CROUCH, RJ TOZAWA, Y CERRITELLI, SM AF CROUCH, RJ TOZAWA, Y CERRITELLI, SM TI RIBONUCLEASES H OF SACCHAROMYCES-CEREVISIAE, SCHIZOSACCHAROMYCES-POMBE AND CRITHIDIA-FASCICULATA SHARE A COMMON MOTH IN THEIR NON-RNASE-H DOMAIN THAT BINDS DOUBLE-STRANDED-RNA IN A MAGNESIUM-DEPENDENT MANNER SO PROTEIN ENGINEERING LA English DT Meeting Abstract C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. RI Tozawa, Yuzuru/G-2657-2013 OI Tozawa, Yuzuru/0000-0002-3885-1105 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 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD SEP PY 1994 VL 7 IS 9 BP 1151 EP 1152 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA PG507 UT WOS:A1994PG50700015 ER PT J AU PAPAC, DI HOYES, J TOMER, KB AF PAPAC, DI HOYES, J TOMER, KB TI EPITOPE MAPPING OF THE GASTRIN-RELEASING PEPTIDE ANTI-BOMBESIN MONOCLONAL-ANTIBODY COMPLEX BY PROTEOLYSIS FOLLOWED BY MATRIX-ASSISTED LASER-DESORPTION IONIZATION MASS-SPECTROMETRY SO PROTEIN SCIENCE LA English DT Article DE AFFINITY CHROMATOGRAPHY; ANTIBODY; BOMBESIN; EPITOPE; MASS SPECTROMETRY; PROTEOLYSIS ID PROTEIN ANTIGEN; RESOLUTION; SITES AB We have developed a method to rapidly identify the antigenic determinant for an antibody using in situ proteolysis of an immobilized antigen-antibody complex followed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI/TOF). A mouse anti-bombesin monoclonal antibody was immobilized to agarose beads and then the antigen, gastrin-releasing peptide (GRP), was allowed to bind. Direct analysis of the immobilized antigen-antibody complex by MALDI/TOF is demonstrated and allows identification of ca. 1 pmol of the bound GRP. To identify the epitope, the immobilized antigen-antibody complex was subjected to proteolysis with trypsin, chymotrypsin, thermolysin, and aminopeptidase M. Following proteolysis, the part of the antigen in contact with the antibody and protected from proteolysis was identified directly by MALDI/TOF. Subsequently, the epitope was eluted from the immobilized antibody with 0.1 M glycine buffer (pH 2.3), separated by reversed-phase HPLC, and its identity confirmed by MALDI/TOF. Using this approach, the epitope for the anti-bombesin monoclonal antibody was shown to comprise the last 7-8 residues (HWAVGHLM-NH2) of GRP. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. FISONS VG ANALYT,MANCHESTER M23 9LE,LANCS,ENGLAND. RI Tomer, Kenneth/E-8018-2013 NR 26 TC 64 Z9 67 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD SEP PY 1994 VL 3 IS 9 BP 1485 EP 1492 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PK830 UT WOS:A1994PK83000014 PM 7530543 ER PT J AU PARISEAU, C GREGOR, P MYLESWORSLEY, M HOLIK, J HOFF, M WALDO, M FREEDMAN, R COON, H BYERLEY, W AF PARISEAU, C GREGOR, P MYLESWORSLEY, M HOLIK, J HOFF, M WALDO, M FREEDMAN, R COON, H BYERLEY, W TI SCHIZOPHRENIA AND GLUTAMATE-RECEPTOR GENES SO PSYCHIATRIC GENETICS LA English DT Article DE SCHIZOPHRENIA; LINKAGE ANALYSIS; GLUTAMATE RECEPTOR GENES ID AMYOTROPHIC-LATERAL-SCLEROSIS; CHROMOSOMAL LOCALIZATION; LINKAGE ANALYSIS; SUBUNIT NMDAR1; HUMANS; GLUR5 AB Nine multiplex schizophrenia families were genotyped with polymorphisms for the GLUR5 and NMDAR1 glutamate receptor subunit genes. Using the lod score technique, evidence of linkage was not found assuming either dominant or recessive transmission. Similarly, the non-parametric sib pair test did not yield significant evidence of linkage. C1 UNIV UTAH,MED CTR,DEPT PSYCHIAT,SALT LAKE CITY,UT 84132. NIDA,ADDICT RES CTR,MOLEC NEUROBIOL BRANCH,BALTIMORE,MD 21224. UNIV COLORADO,HLTH SCI CTR,DEPT PSYCHIAT,DENVER,CO 80262. FU NIMH NIH HHS [MH44212, 5F32MH10168, KO2 MH01089] NR 40 TC 6 Z9 6 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0955-8829 J9 PSYCHIATR GENET JI Psychiatr. Genet. PD FAL PY 1994 VL 4 IS 3 BP 161 EP 165 DI 10.1097/00041444-199400430-00006 PG 5 WC Genetics & Heredity; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA QA186 UT WOS:A1994QA18600006 PM 7719702 ER PT J AU GRACE, WC FERNANDEZ, MI BATTJES, RJ SLOBODA, Z GENSER, SG AF GRACE, WC FERNANDEZ, MI BATTJES, RJ SLOBODA, Z GENSER, SG TI ORGANIZATIONAL-PSYCHOLOGY PERSPECTIVES ON ENHANCING NATIONAL HIV PREVENTION RESEARCH AMONG DRUG-ABUSERS SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article AB A meeting sponsored by the National Institute on Drug Abuse was held to conduct an organizational analysis of research efforts in HIV prevention among those at risk through drug abuse. The analysis focused on enhancing research collaboration to facilitate innovative studies. Findings clarified how organizational cultures support academic or service values that influence the types of research accomplished. The impacts of organizational missions, structure, leadership, and reward systems on researchers' willingness and abilities to collaborate were also addressed. Understanding these themes should better enable researchers in various sites to develop and pursue collaborative efforts. C1 NIDA,ROCKVILLE,MD. NIMH,ROCKVILLE,MD 20857. NR 12 TC 1 Z9 1 U1 0 U2 0 PU EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 SN 0893-164X J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD SEP PY 1994 VL 8 IS 3 BP 191 EP 197 PG 7 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA PW868 UT WOS:A1994PW86800006 ER PT J AU BARRETT, JE GAMBLE, EH ZHANG, L GUARDIOLALEMAITRE, B AF BARRETT, JE GAMBLE, EH ZHANG, L GUARDIOLALEMAITRE, B TI ANTICONFLICT AND DISCRIMINATIVE STIMULUS EFFECTS IN THE PIGEON OF A NEW METHOXY-CHROMAN 5-HT1A AGONIST, (+)S-20244 AND ITS ENANTIOMERS (+)S-20499 AND (-)S-20500 SO PSYCHOPHARMACOLOGY LA English DT Article DE CONFLICT PROCEDURE; PUNISHMENT; 5-HT1A; DRUG DISCRIMINATION; ANXIETY; DEPRESSION; ANIMAL MODEL; 8-OH-DPAT; (+)S 20244, (+)S 20499; (-)S 20500; PIGEON ID GENERALIZED ANXIETY DISORDER; ANXIOLYTIC DRUGS; BUSPIRONE; GEPIRONE; DIAZEPAM; RATS AB The present experiments examined the behavioral and receptor binding characteristics of new 5-HT1A methoxy-chroman derivatives in procedures known to be sensitive to the activity of 5-HT1A compounds. Key peck responding of pigeons was maintained by a 30-response fixed-ratio schedule of food delivery. In studies involving punished responding, every 30th response during one keylight stimulus also produced shock (''conflict'' procedure). In drug discrimination studies, pigeons were trained to discriminate injections of the 5-HT1A agonist 8-OH-DPAT (0.3 mg/kg) from saline. Three forms of the methoxy-chroman compounds were tested: the enantiomers (+)S 20499 (0.01-3.0 mg/kg) and (-)S 20500 (0.3-5.6 mg/kg), as well as the racemic mixture (+)S 20244 (0.03-5.6 mg/kg). (+)S 20499 was approximately 10-fold more potent than (-)S 20500 in producing maximal increases in punished responding. (+)S 20244 was comparable in potency to (-)S 20500 in producing maximal increases in punished responding, but increases also occurred at much lower doses with (+)S 20244 and the magnitude of the effect with (-)S 20500 was less than that of the two other compounds. While increases in punished responding were observed with all three drugs at doses that did not affect unpunished responding, the highest doses of all drugs decreased unpunished responding. All compounds substituted for 8-OH-DPAT in the drug discrimination procedure, suggestive of 5-HT1A agonist activity. (+)S 20499 was approximately 30-fold more potent than (-)S 20500 in substituting for 8-OH-DPAT and 3-fold more potent than the racemate. All three compounds bound with high affinity to pigeon cerebrum receptor sites labelled by [H-3]8-OH-DPAT. As in behavioral studies, (+)S 20499 was approximately 10-fold more potent than (-)S 20500 in displacing [H-3]8-OH-DPAT (IC50 = 2.79 versus 20.3 nM). These studies demonstrate that the enantiomers of this compound, as well as the racemic mixture, are effective 5-HT1A compounds and that (+)S 20499 in particular is likely to be a clinically effective anxiolytic and/or antidepressant. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT PSYCHIAT,BETHESDA,MD 20814. NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. INST RECH INT SERVIER,F-92415 COURBEVOIE,FRANCE. RP BARRETT, JE (reprint author), AMER CYANAMID CO,LEDERLE LABS,CENT NERVOUS SYST RES,PEARL RIVER,NY 10965, USA. NR 26 TC 17 Z9 17 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD SEP PY 1994 VL 116 IS 1 BP 73 EP 78 DI 10.1007/BF02244873 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA PF526 UT WOS:A1994PF52600010 PM 7862933 ER PT J AU ENGEL, BT AF ENGEL, BT TI DEVELOPMENTAL PSYCHOBIOLOGY - NEW METHODS AND CHANGING CONCEPTS - SHAIR,HN, BARR,GA, HOFER,MA SO PSYCHOSOMATIC MEDICINE LA English DT Book Review RP ENGEL, BT (reprint author), NIA,GERONTOL RES CTR,BEHAV SCI LAB,BALTIMORE,MD 21224, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD SEP-OCT PY 1994 VL 56 IS 5 BP 476 EP 477 PG 2 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA PK285 UT WOS:A1994PK28500015 ER PT J AU POLONSKY, S KERR, S HARRIS, B GAITER, J FICHTNER, RR KENNEDY, MG AF POLONSKY, S KERR, S HARRIS, B GAITER, J FICHTNER, RR KENNEDY, MG TI HIV PREVENTION IN PRISONS AND JAILS - OBSTACLES AND OPPORTUNITIES SO PUBLIC HEALTH REPORTS LA English DT Article ID DRUG-ABUSERS; AIDS; INMATES; ADOLESCENTS; INFECTION; KNOWLEDGE; ATTITUDES; BEHAVIORS; RISK; CARE AB High rates of human immunodeficiency virus (HIV) infection among jail and prison inmates suggest that HIV prevention efforts should focus on incarcerated populations. Overcrowding, the high prevalence of injection drug use, and other high-risk behaviors among inmates create a prime opportunity for public health officials to affect the course of the HIV epidemic if they can remedy these problems. Yet, along with the opportunity, there are certain obstacles that correctional institutions present to public health efforts. The various jurisdictions have differing approaches to HIV prevention and control. Whether testing should be mandatory or voluntary, whether housing should be integrated or segregated by HIV serostatus, and whether condoms, bleach, or clean needles should be made available to the prisoners, are questions hotly debated by public health and correctional officials. Even accurate assessment of risk-taking within the institutions leads to controversy, as asking questions could imply acceptance of the very behaviors correctional officials are trying to prevent. Education and risk-reduction counseling are the least controversial and most widely employed modes of prevention, but the effectiveness of current prevention efforts in reducing HIV transmission in this high-risk population is largely undertermined. C1 UNIV N CAROLINA,SCH CYTOL & GENET,BEHAV STUDIES SECT,CHAPEL HILL,NC 27514. UNIV N CAROLINA,SCH PUBL HLTH,BEHAV & PREVENT RES BRANCH,CHAPEL HILL,NC 27514. EMORY UNIV,SCH PUBL HLTH,NIMH,AIDS TRAINING PROGRAM,ATLANTA,GA 30322. RP KERR, S (reprint author), CTR DIS CONTROL & PREVENT,NATL CTR PREVENT SERV,DIV STD HIV PREVENT,BEHAV & PREVENT RES BRANCH,ATLANTA,GA 30333, USA. NR 56 TC 47 Z9 49 U1 1 U2 4 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD SEP-OCT PY 1994 VL 109 IS 5 BP 615 EP 625 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PN152 UT WOS:A1994PN15200005 PM 7938381 ER PT J AU GANIKOS, ML MCNEIL, C BRASLOW, JB ARKIN, EB KLAUS, D OBERLEY, EE WHITE, MF AF GANIKOS, ML MCNEIL, C BRASLOW, JB ARKIN, EB KLAUS, D OBERLEY, EE WHITE, MF TI A CASE-STUDY IN PLANNING FOR PUBLIC-HEALTH EDUCATION - THE ORGAN AND TISSUE DONATION EXPERIENCE SO PUBLIC HEALTH REPORTS LA English DT Article AB The chasm between the supply and demand of donated organs and tissues continues to grow despite widespread public awareness of transplantation and numerous efforts to educate the public about organ donation. It is fast becoming a significant public health problem in this country. The need for more effective public education is well documented in the literature on transplantation and is a primary objective of organizations in the transplant field. In response to this need, the Division of Organ Transplantation in the Health Resources and Services Administration of the Public Health Service initiated a project to examine the nature and scope of donation education initiatives throughout the country, to identify shortcomings, and to suggest ways the Federal Government could contribute to the effectiveness of public education in organ and tissue donation. The project resulted in the development of a protocol that also is applicable to other health education programs. Its major steps consisted of assessing the status of donation-related public education in the United States, identifying existing needs in donation education by applying principles learned from other public health education programs, and identifying roles that could be assumed to help strengthen the American public's commitment to organ and tissue donation. These roles, which could be adopted by any transplant-related organization, were as broker of knowledge, producer of educational strategies, energizer through communications research, and catalyst by bringing together other groups. This approach to needs assessment and planning may provide useful insights both for those concerned with transplants and for professionals conducting education campaigns related to other public health issues. C1 NIA,BETHESDA,MD 20892. UNIV RES CORP,DONAT EDUC PROJECT,BETHESDA,MD. MED MEDIA ASSOCIATES,MADISON,WI. MICHAEL F WHITE & ASSOCIATES,ALEXANDRIA,VA. RP GANIKOS, ML (reprint author), US HLTH RESOURCES & SERV ADM,US BUR HLTH RESOURCES DEV,DIV ORGAN TRANSPLANTAT,PARKLAWN BLDG,ROCKVILLE,MD 20857, USA. NR 19 TC 7 Z9 7 U1 1 U2 1 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD SEP-OCT PY 1994 VL 109 IS 5 BP 626 EP 631 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PN152 UT WOS:A1994PN15200006 PM 7938382 ER PT J AU SHEON, AR FOX, HE ALEXANDER, G BUCK, A HIGGINS, A MCDERMOTT, SM MOROSO, G MOYE, J PACHECOACOSTA, E AF SHEON, AR FOX, HE ALEXANDER, G BUCK, A HIGGINS, A MCDERMOTT, SM MOROSO, G MOYE, J PACHECOACOSTA, E TI MISDIAGNOSED HIV-INFECTION IN PREGNANT-WOMEN - IMPLICATIONS FOR CLINICAL CARE SO PUBLIC HEALTH REPORTS LA English DT Note ID HUMAN-IMMUNODEFICIENCY-VIRUS; FALSE POSITIVE RATE; MUNCHAUSEN AIDS AB Out of nearly 900 women in a research study of human immunodeficiency virus infection in pregnancy, 8 were subsequently found not to be infected. Misdiagnoses could have resulted from (a) laboratory errors or specimen mixups; (b) failure to follow the testing algorithm recommended by the Centers for Disease Control and Prevention to confirm results; (c) women perceiving they were infected by high-risk behavior in the absence of testing, despite the receipt of negative test results, or based on screening results only; or (d) factitious disorder, HIV Munchausen syndrome, or malingering. Because of the potentially devastating impact of an HIV diagnosis and the toxicity of HIV therapies, health care providers should obtain independent confirmation of the diagnosis before initiating treatment or followup for HIV based on patient report or provider referral. Quality test interpretation and counseling must be ensured. Therapeutic interventions may be indicated for persons intentionally and falsely presenting themselves as HIV-infected. C1 NEW ENGLAND RES INST,WATERTOWN,MA. COLUMBIA PRESBYTERIAN MED CTR,DEPT OBSTET & GYNECOL,NEW YORK,NY 10032. UNIV ILLINOIS,CHICAGO,IL 60680. COLUMBIA PRESBYTERIAN MED CTR,CTR WOMEN & CHILDRENS CARE,NEW YORK,NY 10032. SUNY DOWNSTATE MED CTR,HLTH SCI CTR,BROOKLYN,NY. NICHHD,ADOLESCENT & MATERNAL AIDS BRANCH,BETHESDA,MD. UNIV PUERTO RICO,RIO PIEDRAS,PR 00931. RP SHEON, AR (reprint author), NIAID,DIV AIDS,6003 EXECUT BLVD,ROCKVILLE,MD 20892, USA. OI moye, john/0000-0001-9976-8586 FU NIAID NIH HHS [N01-AI-82505, N01-AI-82506, N01-AI-82507] NR 27 TC 6 Z9 6 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD SEP-OCT PY 1994 VL 109 IS 5 BP 694 EP 699 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PN152 UT WOS:A1994PN15200016 PM 7938392 ER PT J AU CHOYKE, PL AF CHOYKE, PL TI STATE-OF-THE-ART MR-IMAGING OF THE ADRENAL-GLAND SO RADIOGRAPHICS LA English DT Note ID MASSES; CT; BIOPSY; BENIGN RP CHOYKE, PL (reprint author), NIH,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892, USA. NR 15 TC 1 Z9 1 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD SEP PY 1994 VL 14 IS 5 BP 1029 EP 1032 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PG637 UT WOS:A1994PG63700011 ER PT J AU WOLFF, SD BALABAN, RS AF WOLFF, SD BALABAN, RS TI MAGNETIZATION-TRANSFER IMAGING - PRACTICAL ASPECTS AND CLINICAL-APPLICATIONS SO RADIOLOGY LA English DT Article DE MAGNETIC RESONANCE (MR), EXPERIMENTAL; MAGNETIC RESONANCE (MR), MAGNETIZATION TRANSFER CONTRAST; STATE-OF-ART REVIEWS ID WATER PROTON RELAXATION; TRANSFER CONTRAST; PULSED SATURATION; MR ANGIOGRAPHY; FAT SATURATION; TISSUE; SEQUENCES; SYSTEMS; ABDOMEN; INVIVO C1 JOHNS HOPKINS MED INST,RUSSELL H MORGAN DEPT RADIOL & RADIOL SCI,BALTIMORE,MD 21205. NHLBI,CARDIAC ENERGET LAB,BETHESDA,MD 20892. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 43 TC 209 Z9 211 U1 0 U2 5 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 1994 VL 192 IS 3 BP 593 EP 599 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PD073 UT WOS:A1994PD07300002 PM 8058919 ER PT J AU MAUTNER, GC MAUTNER, SL FROEHLICH, J FEUERSTEIN, IM PROSCHAN, MA ROBERTS, WC DOPPMAN, JL AF MAUTNER, GC MAUTNER, SL FROEHLICH, J FEUERSTEIN, IM PROSCHAN, MA ROBERTS, WC DOPPMAN, JL TI CORONARY-ARTERY CALCIFICATION - ASSESSMENT WITH ELECTRON-BEAM CT AND HISTOMORPHOMETRIC CORRELATION SO RADIOLOGY LA English DT Article DE CORONARY VESSELS, CALCIFICATION; CORONARY VESSELS, CT; CORONARY VESSELS, STENOSIS OR OBSTRUCTION ID ULTRAFAST COMPUTED-TOMOGRAPHY; DISEASE AB PURPOSE: To assess the reliability of electron beam computed tomography (CT) in the detection of calcific deposits in coronary arteries. MATERIALS AND METHODS: The authors quantitatively evaluated a total of 4,298 segments of coronary arteries with electron beam CT and histomorphometry. RESULTS: Regression analysis of the electron beam CT calcium score versus histomorphometric calcium area produced an r(2) value of .92 (r = .96; P < .0001). Ninety-three percent (78 of 84) of all coronary arteries with stenosis of 76%-100% contained calcific deposits, and 20% (17 of 83) of all coronary arteries with stenosis of O%-50% contained calcific deposits. CONCLUSION: The amount of calcific deposits detected with electron beam CT correlates highly with histomorphometric measurements. Also, the amount of calcific deposits correlates well with the degree of coronary artery stenosis. Electron beam CT, therefore, is a promising noninvasive technique that can help depict the presence and extent of atherosclerotic plaques. C1 NHLBI,BIOSTAT RES BRANCH,BETHESDA,MD 20892. NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. RP MAUTNER, GC (reprint author), NHLBI,CTR CLIN,DEPT DIAGNOST RADIOL,BLDG 10,RM 1C660,BETHESDA,MD 20892, USA. NR 37 TC 250 Z9 267 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 1994 VL 192 IS 3 BP 619 EP 623 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PD073 UT WOS:A1994PD07300007 PM 8058924 ER PT J AU MAUTNER, SL MAUTNER, GC FROEHLICH, J FEUERSTEIN, IM PROSCHAN, MA ROBERTS, WC DOPPMAN, JL AF MAUTNER, SL MAUTNER, GC FROEHLICH, J FEUERSTEIN, IM PROSCHAN, MA ROBERTS, WC DOPPMAN, JL TI CORONARY-ARTERY DISEASE - PREDICTION WITH IN-VITRO ELECTRON-BEAM CT SO RADIOLOGY LA English DT Article DE CORONARY VESSELS, CALCIFICATION; CORONARY VESSELS, CT; CORONARY VESSELS, STENOSIS OR OBSTRUCTION ID ULTRAFAST COMPUTED-TOMOGRAPHY; ASYMPTOMATIC MEN; CALCIFICATION; FLUOROSCOPY AB PURPOSE: To investigate the potential to predict coronary artery disease with electron beam computed tomography (CT). MATERIALS AND METHODS: Fifty heart specimens were examined with electron beam CT and histomorphometric techniques to measure calcific deposits as a percentage of blockage. RESULTS: In group A specimens (from cadavers of patients with symptomatic coronary artery disease), calcific deposits were identified at electron beam CT in 41% (584 of 1,426) of all segments of coronary arteries; in group B specimens (with asymptomatic coronary artery disease), in 24% (369 of 1,535) of all segments; and in the normal control specimens, in 4% (47 of 1,337) of all segments (group A vs control specimens, P < .0001; group B vs control specimens, P = .02). On the basis of logistic regression analysis, coronary artery disease would be predicted if the average electron beam CT calcium score exceeds 0.32. The sensitivity and specificity of electron beam CT in the detection of calcific deposits per coronary artery was 94% and 76%, respectively. CONCLUSION: The electron beam CT calcium score appears to be an effective predictor of coronary artery disease. C1 NIH,BIOSTAT RES BRANCH,BETHESDA,MD 20892. NIH,PATHOL BRANCH,BETHESDA,MD 20892. RP MAUTNER, SL (reprint author), NIH,CTR CLIN,DEPT DIAGNOST RADIOL,BLDG 10,RM 1C660,BETHESDA,MD 20892, USA. NR 30 TC 112 Z9 117 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 1994 VL 192 IS 3 BP 625 EP 630 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PD073 UT WOS:A1994PD07300008 PM 8058925 ER PT J AU POSSE, S DECARLI, C LEBIHAN, D AF POSSE, S DECARLI, C LEBIHAN, D TI 3-DIMENSIONAL ECHO-PLANAR MR SPECTROSCOPIC IMAGING AT SHORT ECHO TIMES IN THE HUMAN BRAIN SO RADIOLOGY LA English DT Article DE BRAIN, MR; MAGNETIC RESONANCE (MR), PULSE SEQUENCES; MAGNETIC RESONANCE (MR), RAPID IMAGING; MAGNETIC RESONANCE (MR), SPECTROSCOPY; MAGNETIC RESONANCE (MR), 3-DIMENSIONAL ID CHEMICAL-SHIFT; NMR-SPECTROSCOPY; STIMULATED ECHOES; EXCITATION; TRAINS AB PURPOSE: To demonstrate the feasibility of three-dimensional echo-planar spectroscopic imaging (EPSI) at short echo time (13 msec) with a conventional clinical imager in the human brain. MATERIALS AND METHODS: Periodic inversions of a readout gradient were used during data acquisition to simultaneously encode chemical shift and one spatial dimension in one excitation. Aliasing artifacts were avoided with a modified acquisition-and-processing method based on oversampling. A double outer-volume suppression technique that adapts to the ovoid brain shape was used to strongly reduce extracranial lipid resonances. RESULTS: Three-dimensional spatial encoding in vivo of eight sections with 32 x 32 voxels each (0.75 cm(3)) was performed in 34 minutes with four signal averages. The spectral resolution and signal-to-noise ratio (S/N) of resonances of inositol, choline, creatine, glutamate and glutamine, and N-acetyl aspartate were consistent with those previously recorded with conventional phase encoding. CONCLUSION: EPSI substantially reduces acquisition time for three-dimensional spatial encoding and yields a spectral quality similar to that obtained with conventional techniques without affecting the S/N per unit time and unit volume. C1 NIA,NEUROSCI LAB,BETHESDA,MD. RP POSSE, S (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BLDG 10,RM1C660,BETHESDA,MD 20892, USA. RI DeCarli, Charles/B-5541-2009 NR 27 TC 127 Z9 128 U1 1 U2 8 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD SEP PY 1994 VL 192 IS 3 BP 733 EP 738 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PD073 UT WOS:A1994PD07300025 PM 8058941 ER PT J AU MELBYE, M BIGGAR, RJ AF MELBYE, M BIGGAR, RJ TI A PROFILE OF HIV-RISK BEHAVIORS AMONG TRAVELERS - A POPULATION-BASED STUDY OF DANES VISITING GREENLAND SO SCANDINAVIAN JOURNAL OF SOCIAL MEDICINE LA English DT Article DE HIV; SEX-BEHAVIOR; HETEROSEXUAL TRANSMISSION; EPIDEMIC; MIGRANTS; TRAVELERS; GREENLAND; DENMARK ID DENMARK AB The population of Greenlands has behavioural characteristics that indicate a high risk of HIV spread once HIV is introduced into the population. Much depends, however, on the degree of exposure from visitors, particularly in an initial phase. We used a national questionnaire survey of 4680 randomly selected Danes between 18-59 years to study HIV risk behaviours among Danes with (+travellers) and without (-travellers) travel experience to Greenland. Median number of lifetime sexual partners was more than twice as high among male +travellers (median = 12 partners) compared to -travellers (median = 5; p < 0.0001) and also slightly higher among women (p = 0.03). Furthermore, a significantly higher percentage of male +travellers than -travellers reported prostitute contact (OR = 2.3 (95% CI: 1.4-3.9)), with a peak of 32.0% among men aged 40-49 years. A history of a sexually transmitted disease was three times (95% CI: 2.0-4.5) as common among +travellers as in -travellers. +Travellers were also signficantly more likely to have visited other places outside Europe and Greenland, including HIV endemic areas (OR = 2.9 (2.0-4.1)). Overall, sexual contact with someone considered at high risk of HIV infection (a homo/bisexual man, intravenous drug user, prostitute, or previous or present resident of Sub-Saharan Africa) was reported by 33.5% of male +travellers compared to 15.6% of -travellers and among women by 9.7% and 5.0%, respectively. In conclusion, travellers tend to have more sexual partners and more sexual interaction with high HIV-risk group members than non-travellers. A national intervention programme to prevent HIV spread in Greenland should not only consider campaigns to educate safe sex procedures among the Inuits but also establish an intervention programme for visitors to the island. C1 NCI,DIV CANC ETIL,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. RP MELBYE, M (reprint author), STATE SERUM INST,EPIDEMIOL RES UNIT,ARTILLERIVEJ 5,DK-2300 COPENHAGEN S,DENMARK. NR 11 TC 4 Z9 4 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0300-8037 J9 SCAND J SOC MED JI Scand. J. Soc. Med. PD SEP PY 1994 VL 22 IS 3 BP 204 EP 208 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PR357 UT WOS:A1994PR35700008 PM 7846479 ER EF