FN Thomson Reuters Web of Science™ VR 1.0 PT J AU FLANAGAN, JR BECKER, KG ENNIST, DL GLEASON, SL DRIGGERS, PH LEVI, BZ APPELLA, E OZATO, K AF FLANAGAN, JR BECKER, KG ENNIST, DL GLEASON, SL DRIGGERS, PH LEVI, BZ APPELLA, E OZATO, K TI CLONING OF A NEGATIVE TRANSCRIPTION FACTOR THAT BINDS TO THE UPSTREAM CONSERVED REGION OF MOLONEY MURINE LEUKEMIA-VIRUS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; LONG TERMINAL REPEAT; EMBRYONAL CARCINOMA-CELLS; ZINC FINGER MOTIFS; CLASS-I GENE; DNA-BINDING; RETINOIC ACID; MULTIGENE FAMILY; NUCLEAR FACTORS; KRUPPEL FAMILY AB The long terminal repeat of Moloney murine leukemia virus (MuLV) contains the upstream conserved region (UCR). The UCR core sequence, CGCCATTTT, binds a ubiquitous nuclear factor and mediates negative regulation of MuLV promoter activity. We have isolated murine cDNA clones encoding a protein, referred to as UCRBP, that binds specifically to the UCR core sequence. Gel mobility shift assays demonstrate that the UCRBP fusion protein expressed in bacteria binds the UCR core with specificity identical to that of the UCR-binding factor in the nucleus of murine and human cells. Analysis of full-length UCRBP cDNA reveals that it has a putative zinc finger domain composed of four C2H2 zinc fingers of the GLI subgroup and an N-terminal region containing alternating charges, including a stretch of 12 histidine residues. The 2.4-kb UCRBP message is expressed in all cell lines examined (teratocarcinoma, B- and T-cell, macrophage, fibroblast, and myocyte), consistent with the ubiquitous expression of the UCR-binding factor. Transient transfection of an expressible UCRBP cDNA into fibroblasts results in down-regulation of MuLV promoter activity, in agreement with previous functional analysis of the UCR. Recently three groups have independently isolated human and mouse UCRBP. These studies show that UCRBP binds to various target motifs that are distinct from the UCR motif: the adeno-associated virus P5 promoter and elements in the immunoglobulin light- and heavy-chain genes, as well as elements in ribosomal protein genes. These results indicate that UCRBP has unusually diverse DNA-binding specificity and as such is likely to regulate expression of many different genes. C1 NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892. UNIV IOWA,DEPT INTERNAL MED,IOWA CITY,IA 52242. NCI,CELL BIOL LAB,BETHESDA,MD 20892. OI Becker, Kevin/0000-0002-6794-6656 NR 54 TC 234 Z9 237 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 1992 VL 12 IS 1 BP 38 EP 44 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GW053 UT WOS:A1992GW05300005 PM 1309593 ER PT J AU CHIPEV, CC WOLFFE, AP AF CHIPEV, CC WOLFFE, AP TI CHROMOSOMAL ORGANIZATION OF XENOPUS-LAEVIS OOCYTE AND SOMATIC 5S RIBOSOMAL-RNA GENES INVIVO SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MINICHROMOSOMES ASSEMBLED INVITRO; TRANSCRIPTION FACTOR-IIIA; INTERNAL CONTROL REGION; HIGHER-ORDER STRUCTURE; RIBOSOMAL-RNA GENES; 5S-RNA GENE; POLYMERASE-III; CHROMATIN; HISTONE-H1; DNA AB We describe the chromosomal organization of the major oocyte and somatic 5S RNA genes of Xenopus laevis in chromatin isolated from erythrocyte nuclei. Both major oocyte and somatic 5S DNA repeats are associated with nucleosomes; however, differences exist in the organization of chromatin over the oocyte and somatic 5S RNA genes. The repressed oocyte 5S RNA gene is protected from nuclease digestion by incorporation into a nucleosome, and the entire oocyte 5S DNA repeat is assembled into a loosely positioned array of nucleosomes. In contrast, the potentially active somatic 5S RNA gene is accessible to nuclease digestion, and the majority of somatic 5S RNA genes appear not to be incorporated into positioned nucleosomes. Evidence is presented supporting the stable association of transcription factors with the somatic 5S RNA genes. Histone H1 is shown to have a role both in determining the organization of nucleosomes over the oocyte 5S DNA repeat and in repressing transcription of the oocyte 5S RNA genes. C1 NICHHD,MOLEC EMBRYOL LAB,BLDG 6,ROOM 131,BETHESDA,MD 20892. NR 57 TC 73 Z9 73 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 1992 VL 12 IS 1 BP 45 EP 55 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GW053 UT WOS:A1992GW05300006 PM 1729615 ER PT J AU VEGA, QC COCHET, C FILHOL, O CHANG, CP RHEE, SG GILL, GN AF VEGA, QC COCHET, C FILHOL, O CHANG, CP RHEE, SG GILL, GN TI A SITE OF TYROSINE PHOSPHORYLATION IN THE C-TERMINUS OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR IS REQUIRED TO ACTIVATE PHOSPHOLIPASE-C SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PHOSPHOTYROSINE-CONTAINING PROTEINS; EGF-RECEPTOR; INOSITOL PHOSPHATES; KINASE-ACTIVITY; SIGNAL TRANSDUCTION; CALCIUM; GAMMA; BINDING; CELLS; ONCOGENE AB Cells expressing mutant epidermal growth factor (EGF) receptors have been used to study mechanisms through which EGF increases phospholipase C (PLC) activity. C-terminal truncation mutant EGF receptors are markedly impaired in their ability to increase inositol phosphate formation compared with wild-type EGF receptors. Mutation of the single tyrosine self-phosphorylation site at residue 992 to phenylalanine in an EGF receptor truncated at residue 1000 abolished the ability of EGF to increase inositol phosphate formation. C-terminal deletion mutant receptors that are impaired in their ability to increase inositol phosphate formation effectively phosphorylate PLC-gamma at the same tyrosine residues as do wild-type EGF receptors. EGF enhances PLC-gamma association with wild-type EGF receptors but not with mutant receptors lacking sites of tyrosine phosphorylation. These results indicate that formation of a complex between self-phosphorylated EGF receptors and PLC-gamma is necessary for enzyme activation in vivo. We propose that both binding of PLC-gamma to activated EGF receptors and tyrosine phosphorylation of the enzyme are necessary to elicit biological responses. Kinase-active EGF receptors lacking sites of tyrosine phosphorylation are unable to signal increased inositol phosphate formation and increases in cytosolic Ca2+ concentration. C1 UNIV CALIF SAN DIEGO,SCH MED,DEPT MED,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,SCH MED,DEPT BIOL,LA JOLLA,CA 92093. CEN,INSERM,U244,F-38041 GRENOBLE,FRANCE. NHLBI,BETHESDA,MD 20892. RI Filhol-Cochet, Odile/I-3962-2016 FU NIDDK NIH HHS [DDK13149-24S] NR 47 TC 99 Z9 99 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 1992 VL 12 IS 1 BP 128 EP 135 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GW053 UT WOS:A1992GW05300014 PM 1729595 ER PT J AU SCHWARTZ, S FELBER, BK PAVLAKIS, GN AF SCHWARTZ, S FELBER, BK PAVLAKIS, GN TI MECHANISM OF TRANSLATION OF MONOCISTRONIC AND MULTICISTRONIC HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 MESSENGER-RNAS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GCN4 MESSENGER-RNA; CAP-INDEPENDENT TRANSLATION; 5' NONCODING REGION; EUKARYOTIC RIBOSOMES; PROTEIN-SYNTHESIS; MAMMALIAN-CELLS; POLIOVIRUS RNA; REV PROTEIN; AUG CODONS; HTLV-III AB We have used a panel of cDNA clones expressing wild-type and mutant human immunodeficiency virus type 1 (HIV-1) mRNAs to study translation of these mRNAs in eucaryotic cells. The tat open reading frame (ORF) has a strong signal for translation initiation, while rev and vpu ORFs have weaker signals. The expression of downstream ORFs is inhibited in mRNAs that contain the tat ORF as the first ORF. In contrast, downstream ORFs are expressed efficiently from mRNAs that have rev or vpu as the first ORF. All env mRNAs contain the upstream vpu ORF. Expression of HIV-1 Env protein requires a weak vpu AUG, which allows leaky scanning to occur, thereby allowing ribosomes access to the downstream env ORF. We concluded that HIV-1 mRNAs are translated by the scanning mechanism and that expression of more than one protein from each mRNA was caused by leaky scanning at the first AUG of the mRNA. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,HUMAN RETROVIRUS SECT,FREDERICK,MD 21702. KAROLINSKA INST,DEPT VIROL,S-10401 STOCKHOLM 60,SWEDEN. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,HUMAN RETROVIRUS PATHOGENESIS GRP,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 85 TC 96 Z9 98 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 1992 VL 12 IS 1 BP 207 EP 219 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GW053 UT WOS:A1992GW05300023 PM 1729599 ER PT J AU MIETZ, JA FEWELL, JW KUFF, EL AF MIETZ, JA FEWELL, JW KUFF, EL TI SELECTIVE ACTIVATION OF A DISCRETE FAMILY OF ENDOGENEOUS PROVIRAL ELEMENTS IN NORMAL BALB/C LYMPHOCYTES SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INTRACISTERNAL-A-PARTICLE; LONG TERMINAL REPEAT; EMBRYONAL CARCINOMA-CELLS; NUCLEOTIDE-SEQUENCE; HEMATOPOIETIC-CELLS; PROMOTER ACTIVITY; GENE-EXPRESSION; MOUSE; DNA; GENOME AB Intracisternal A-particle (IAP) proviral elements are abundant and widely dispersed in the mouse genome. IAP-related transcripts have been detected in normal mouse tissues where expression is under genetic control. In this study, we sought to determine whether IAP expression in BALB/c thymus and lipopolysaccharide-stimulated B cells was due to selective or indiscriminate activation of IAP elements. cDNA libraries were prepared from each source. A total of 86 IAP cDNA clones were isolated from both libraries, and 37 of these were sequenced over a common 0.7- to 1.0-kb region of the IAP genome that included the 3' long terminal repeat (LTR). Three highly related families of elements were found to be expressed in the two cell types examined. All of the related elements had a distinctive U3 regulatory region. Thirteen individual IAP proviral elements were distinguished on the basis of sequence differences within the R region of the LTR. Hybridization of genomic DNA with element-specific oligonucleotide probes confirmed the presence of a restricted number of proviral copies in the lymphocyte-specific family of elements. Most of these copies were found to be methylated in the lymphocyte DNA, but at least seven were hypomethylated in their 5' LTRs. This study shows that activation of IAP elements in normal normal mouse lymphocytes is highly selective. Activation is probably a function of both sequence specificity and methylation status of the proviral LTR. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 43 TC 29 Z9 29 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 1992 VL 12 IS 1 BP 220 EP 228 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GW053 UT WOS:A1992GW05300024 PM 1729601 ER PT J AU NICKAS, G MEYERS, J HEBSHI, LD ASHWELL, JD GOLD, DP SYDORA, B UCKER, DS AF NICKAS, G MEYERS, J HEBSHI, LD ASHWELL, JD GOLD, DP SYDORA, B UCKER, DS TI SUSCEPTIBILITY TO CELL-DEATH IS A DOMINANT PHENOTYPE - TRIGGERING OF ACTIVATION-DRIVEN T-CELL DEATH INDEPENDENT OF THE T-CELL ANTIGEN RECEPTOR COMPLEX SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CYCLOSPORINE-A; TRANSGENIC MICE; MONOCLONAL-ANTIBODY; DNA FRAGMENTATION; CO-EXPRESSION; PHORBOL ESTER; CYCLE BLOCK; THYMOCYTES; HYBRIDOMAS; DELETION AB The failure of Thy-1 and Ly-6 to trigger interleukin-2 production in the absence of surface T-cell antigen receptor complex (TCR) expression has been interpreted to suggest that functional signalling via these phosphatidylinositol-linked alternative activation molecules is dependent on the TCR. We find, in contrast, that stimulation of T cells via Thy-1 or Ly-6 in the absence of TCR expression does trigger a biological response, the cell suicide process of activation-driven cell death. Activation-driven cell death is a process of physiological cell death that likely represents the mechanism of negative selection of T cells. The absence of the TCR further reveals that signalling leading to activation-driven cell death and to lymphokine production are distinct and dissociable. In turn, the ability of alternative activation molecules to function in the absence of the TCR raises another issue: why immature T cells, thymomas, and hybrids fail to undergo activation-driven cell death in response to stimulation via Thy-1 and Ly-6. One possibility is that these activation molecules on immature T cells are defective. Alternatively, susceptibility to activation-driven cell death may be developmentally regulated by TCR-independent factors. We have explored these possibilities with somatic cell hybrids between mature and immature T cells, in which Thy-1 and Ly-6 are contributed exclusively by the immature partner. The hybrid cells exhibit sensitivity to activation-driven cell death triggered via Thy-1 and Ly-6. Thus, the Thy-1 and Ly-6 molecules of the immature T cells can function in a permissive environment. Moreover, with regard to susceptibility to Thy-1 and Ly-6 triggering, the mature phenotype of sensitivity to cell death is genetically dominant. C1 MED BIOL INST,DIV IMMUNOL,11077 N TORREY PINES RD,LA JOLLA,CA 92037. NCI,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,SCH MED,DEPT MICROBIOL & IMMUNOL,LOS ANGELES,CA 90024. NR 37 TC 25 Z9 25 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 1992 VL 12 IS 1 BP 379 EP 385 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GW053 UT WOS:A1992GW05300041 PM 1346063 ER PT J AU RUDIKOFF, S FITCH, WM HELLER, M AF RUDIKOFF, S FITCH, WM HELLER, M TI EXON-SPECIFIC GENE CORRECTION (CONVERSION) DURING SHORT EVOLUTIONARY PERIODS - HOMOGENIZATION IN A 2-GENE FAMILY ENCODING THE BETA-CHAIN CONSTANT REGION OF THE LYMPHOCYTE-T ANTIGEN RECEPTOR SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE GENE CONVERSION; LYMPHOCYTE-T ANTIGEN RECEPTOR; GENUS MUS ID GLOBIN GENES; RECOMBINATION; SEQUENCE; CHICKEN; MICE; ORGANIZATION; POLYMORPHISM; MUTATIONS; MUTANTS; EVENTS AB The two genes encoding the beta-chain constant region of the T-lymphocyte antigen receptor appear to have undergone gene conversion in a number of species, including wild and laboratory mice. To examine the frequency of such events during short evolutionarY Periods, we have characterized the corresponding genes from an African pygmy mouse, Mus minutoides. Sequence analysis indicates that exon 1 regions from these genes have undergone conversion events independent of those observed in other mouse species. Furthermore, the conversion events in all murine species are limited to exon 1 sequences. One such event involves the insertion and subsequent transfer of an entire codon between the two genes. Comparisons with other murine C-beta sequences suggest that gene conversion has occurred on the order of every 0.3 Myr during the evolution of a family consisting of only two genes. C1 UNIV CALIF IRVINE,DEPT ECOL & EVOLUT BIOL,IRVINE,CA 92717. RP RUDIKOFF, S (reprint author), NCI,GENET LAB,BLDG 37,ROOM 2B15,BETHESDA,MD 20892, USA. NR 32 TC 21 Z9 21 U1 0 U2 0 PU SOC MOLECULAR BIOLOGY EVOLUTION PI LAWRENCE PA PO BOX 1897, LAWRENCE, KS 66044-8897 SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD JAN PY 1992 VL 9 IS 1 BP 14 EP 26 PG 13 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA GX794 UT WOS:A1992GX79400002 PM 1532437 ER PT J AU HUDSON, RR BOOS, DD KAPLAN, NL AF HUDSON, RR BOOS, DD KAPLAN, NL TI A STATISTICAL TEST FOR DETECTING GEOGRAPHIC SUBDIVISION SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE GEOGRAPHIC SUBDIVISION; MIGRATION; PERMUTATION TEST; NUCLEOTIDE POLYMORPHISM ID DROSOPHILA-MELANOGASTER; RECOMBINATION; LOCUS; DNA AB A statistical test for detecting genetic differentiation of subpopulations is described that uses molecular variation in samples of DNA sequences from two or more localities. The statistical significance of the test is determined with Monte Carlo simulations. The power of the test to detect genetic differentiation in a selectively neutral Wright-Fisher island model depends on both sample size and the rates of migration, mutation, and recombination. It is found that the power of the test is substantial with samples of size 50, when 4Nm < 10, where N is the subpopulation size and m is the fraction of migrants in each subpopulation each generation. More powerful tests are obtained with genes with recombination than with genes without recombination. C1 NIEHS,DEPT STAT,RES TRIANGLE PK,NC 27709. N CAROLINA STATE UNIV,DEPT STAT,RALEIGH,NC 27695. RP HUDSON, RR (reprint author), UNIV CALIF IRVINE,DEPT ECOL & EVOLUT BIOL,IRVINE,CA 92717, USA. FU NIGMS NIH HHS [GM42447] NR 20 TC 646 Z9 652 U1 2 U2 42 PU SOC MOLECULAR BIOLOGY EVOLUTION PI LAWRENCE PA PO BOX 1897, LAWRENCE, KS 66044-8897 SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD JAN PY 1992 VL 9 IS 1 BP 138 EP 151 PG 14 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA GX794 UT WOS:A1992GX79400010 PM 1552836 ER PT J AU MAH, VH ESKIN, TA KAZEE, AM LAPHAM, L HIGGINS, GA AF MAH, VH ESKIN, TA KAZEE, AM LAPHAM, L HIGGINS, GA TI INSITU HYBRIDIZATION OF CALCIUM CALMODULIN DEPENDENT PROTEIN KINASE-II AND TAU-MESSENGER RNAS - SPECIES-DIFFERENCES AND RELATIVE PRESERVATION IN ALZHEIMERS-DISEASE SO MOLECULAR BRAIN RESEARCH LA English DT Article DE NEUROFIBRILLARY TANGLE; PAIRED HELICAL FILAMENT; PHOSPHORYLATION ID PAIRED HELICAL FILAMENTS; CENTRAL NERVOUS-SYSTEM; POSTSYNAPTIC DENSITY; RAT-BRAIN; PHOSPHORYLATION; LOCALIZATION; COMPONENT; LONG; EXPRESSION; SEQUENCES AB Abnormal phosphorylation of the microtubule associated protein tau component of neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) may result from alterations in protein kinase expression. Calcium/calmodulin dependent protein kinase II (CaM kinase II) has been shown to phosphorylate tau in vitro in such a way to decrease its electrophoretic mobility. A68, apparently a modified form of tau in AD brain, also shows abnormal phosphorylation and slower mobility than tau. To further examine the role of CaM kinase II in AD, in situ hybridization studies were performed on tissues from rat, monkey and human to examine and compare the patterns of CaM kinase II mRNA expression in different brain regions. The most notable differences among the three species were observed in dendrites in layer I of isocortex, in the molecular layer of the dentate gyrus and stratum radiatum and stratum lacunosum-moleculare in hippocampus, where hybridization was detected in rat, but not in monkey or human brain. In addition, comparisons between tau and CaM kinase II mRNA expression were made in tissue from normal aged adults and AD patients, especially in areas prone to NFT formation. CaM kinase II and tau mRNAs were co-expressed in many neuronal populations, both those which are prone to NFT formation as well as those which are rarely affected by AD changes. No major differences in the relative abundance of either CaM kinase II or tau mRNA within particular neuronal populations was noted between normal aged and AD brain. Diminished hybridization was associated with serve neuronal pathology and cell loss. C1 UNIV ROCHESTER,MED CTR,DEPT NEUROBIOL & ANAT,ROCHESTER,NY 14642. UNIV ROCHESTER,MED CTR,DEPT PATHOL,ROCHESTER,NY 14642. NIA,GERONTOL RES CTR,MOLEC NEUROBIOL SECT,BALTIMORE,MD 21224. RP MAH, VH (reprint author), THOMAS JEFFERSON UNIV,DEPT NEUROL,DIV NEUROPATHOL,130 S 9TH ST,SUITE 400,PHILADELPHIA,PA 19107, USA. NR 37 TC 33 Z9 33 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 JAN PY 1992 VL 12 IS 1-3 BP 85 EP 94 DI 10.1016/0169-328X(92)90071-I PG 10 WC Neurosciences SC Neurosciences & Neurology GA GZ100 UT WOS:A1992GZ10000010 ER PT J AU KARTASOVA, T ROOP, DR YUSPA, SH AF KARTASOVA, T ROOP, DR YUSPA, SH TI RELATIONSHIP BETWEEN THE EXPRESSION OF DIFFERENTIATION-SPECIFIC KERATIN-1 AND KERATIN-10 AND CELL-PROLIFERATION IN EPIDERMAL TUMORS SO MOLECULAR CARCINOGENESIS LA English DT Article DE KERATINOCYTES; KERATIN-1; KERATIN-10; PAPILLOMA; CARCINOMA ID MOUSE SKIN CARCINOGENESIS; GENE-EXPRESSION; TERMINAL DIFFERENTIATION; MONOSPECIFIC ANTIBODIES; GROWTH; KERATINOCYTES; TRANSFECTION; FIBROBLASTS; EPITHELIA; PEPTIDES AB In normal epidermis, the expression of keratins 1 and 10 is associated with the loss of proliferative capacity and the onset of terminal differentiation. Keratins 1 (K1)and 10 (K10) are commonly expressed in the differentiating layer of benign tumors, but are lost during progression from the benign to the malignant state in skin carcinogenesis. Active gene constructs of mouse K1 and K10 were introduced into papilloma and carcinoma cell lines derived from keratinocytes to analyze the consequences of the expression of these keratins on the organization of the endogenous cytoskeletal network and on the mitotic activity of the recipient cells. Exogenous K1 integrated into the preexisting keratin K5/K14 network of both SLC-1 carcinoma and 308 papilloma cells. The formation of a recombinant cytoskeleton was more restricted for K10 than for K1 and appeared to be related to a requirement for cessation of cell division before K10 could integrate. The integration of exogenous Kl filaments into the endogenous keratin network was compatible with sustained proliferation of SLC-1 carcinoma cells in vitro. However, the exogenous gene was not expressed in tumor grafts in vivo. In contrast, stable K1 or K10 transfectants could not be selected in 308 cells, suggesting that benign tumor cells expressing suprabasal keratins cannot sustain proliferation. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BLDG 37,ROOM 3B25,BETHESDA,MD 20892. BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. NR 29 TC 33 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 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PY 1992 VL 6 IS 1 BP 18 EP 25 DI 10.1002/mc.2940060105 PG 8 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA JJ227 UT WOS:A1992JJ22700004 PM 1380247 ER PT J AU CIARDIELLO, F GOTTARDIS, M BASOLO, F PEPE, S NORMANNO, N DICKSON, RB BIANCO, AR SALOMON, DS AF CIARDIELLO, F GOTTARDIS, M BASOLO, F PEPE, S NORMANNO, N DICKSON, RB BIANCO, AR SALOMON, DS TI ADDITIVE EFFECTS OF C-ERBB-2, C-HA-RAS, AND TRANSFORMING GROWTH FACTOR-ALPHA GENES ON INVITRO TRANSFORMATION OF HUMAN MAMMARY EPITHELIAL-CELLS SO MOLECULAR CARCINOGENESIS LA English DT Article DE TRANSFORMATION; GROWTH FACTORS; MAMMARY CELLS ID HUMAN-BREAST CANCER; TRANSGENIC MICE; FACTOR RECEPTOR; TGF-ALPHA; NEU ONCOGENE; MULTISTEP CARCINOGENESIS; RETROVIRAL VECTOR; TUMOR SUPPRESSOR; PROTO-ONCOGENE; EGF RECEPTOR AB MCF-10A cells are a spontaneously immortalized untransformed human mammary epithelial cell line. We have previously shown that overexpression of a human point-mutated c-Ha-ras proto-oncogene, the rat c-neu (c-erbB-2) proto-oncogene, or the human transforming growth factor-alpha (TGF-alpha) gene in MCF-10A cells leads to in vitro transformation of such cells. To ascertain whether the introduction of two of these genes into MCF-10A human mammary epithelial cells induces a completely tumorigenic phenotype, we infected MCF-10A Ha-ras and MCF-10A TGF-alpha cells with a recombinant retroviral vector containing the human c-erbB-2 proto-oncogene and the hygromycin-resistance gene. Ten MCF-10A TGF-alpha/c-erbB-2 (MCF-10A TE) and 10 MCF-10A Ha-ras/c-erbB-2 (MCF-10A HE) hygromycin-resistant clones were randomly selected and expanded into cell lines. MCF-10A TE and MCF-10A HE clones expressed a 10-fold to 40-fold increase in p185 erbB-2 protein levels compared with parental uninfected cells. These cells exhibited a fourfold increase in their growth rate in serum-free medium and showed a strongly reduced mitogenic response to exogenous epidermal growth factor or TGF-alpha compared with MCF-10A cells. Moreover, both MCF-10A TE and MCF-10A HE clones exhibited a fivefold to 20-fold higher cloning efficiency in soft agar than MCF-10A Ha-ras, MCF-10A c-erbB-2, or MCF-10A TGF-alpha clones. However, neither MCF-10A TE nor MCF-10A HE cells were able to grow as tumors in vivo when they were injected into nude mice. These results suggest that c-Ha-ras, c-erbB-2, and TGF-alpha genes have an additive effect on the in vitro transformation of an immortalized human mammary epithelial cell line, but that additional genetic changes such as activation of other proto-oncogenes or inactivation of a tumor suppressor gene may be necessary to elicit a fully tumorigenic phenotype. C1 GEORGETOWN UNIV,SCH MED,VINCENT LOMBARDI CANC RES CTR,WASHINGTON,DC 20057. FAC MED & CHIRURG,IST ANAT & ISTOL PATOL,PISA,ITALY. NCI,TUMOR IMMUNOL & BIOL,TUMOR GROWTH FACTOR SECT,BETHESDA,MD 20892. RP CIARDIELLO, F (reprint author), FAC MED & CHIRURG,CATTEDRA ONCOL MED,VIA S PANSINI 5,I-80131 NAPLES,ITALY. NR 65 TC 68 Z9 68 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. PY 1992 VL 6 IS 1 BP 43 EP 52 DI 10.1002/mc.2940060108 PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA JJ227 UT WOS:A1992JJ22700007 PM 1354442 ER PT J AU KAHN, T FRIESL, H COPELAND, NG GILBERT, DJ JENKINS, NA GISSMANN, L KRAMER, J HAUSEN, HZ AF KAHN, T FRIESL, H COPELAND, NG GILBERT, DJ JENKINS, NA GISSMANN, L KRAMER, J HAUSEN, HZ TI MOLECULAR-CLONING, ANALYSIS, AND CHROMOSOMAL LOCALIZATION OF A MOUSE GENOMIC SEQUENCE RELATED TO THE HUMAN PAPILLOMAVIRUS TYPE-18 E5-REGION SO MOLECULAR CARCINOGENESIS LA English DT Article DE DNA AMPLIFICATION; RNA OVEREXPRESSION; MAPPING; DIMETHYLBENZ[A]ANTHRACENE; SKIN TUMORS ID EPIDERMAL GROWTH-FACTOR; CERVICAL-CARCINOMA CELLS; TRANSFORMING ACTIVITY; INSITU HYBRIDIZATION; FACTOR-ALPHA; LINKAGE MAP; PROTEIN; GENE; DNA; TRANSCRIPTION AB The E5 open reading frame (ORF) from bovine papillomavirus type 1 (BPV 1) as well as the E5 ORFs from human papillomaviruses (HPV) type 6 and type 16 have been reported to transform immortalized rodent cells. In an analysis of murine and human tumors for the presence of putative papillomavirus-related sequences, we cloned amplified cellular sequences from the mouse cell line Eb that cross-hybridized with the E5 ORF of HPV 18. A 2.1-kb fragment termed HC1 was sequenced. In normal murine cells, it was present as a single-copy genomic sequence located on chromosome 8. A region of 213 nucleotides corresponded to the E5 gene (HC1 E5), based on the best alignments and on the presence of direct and inverted repeats bearing a central sequence motif. These structural elements are also present in the HPV 18 E5 ORF. HC1 E5 contained an ORF that was transcribed bidirectionally. The transcription in the E5 direction was enhanced in RNA obtained from organs and tumors from carcinogen-treated animals and C127 cells. The polypeptide deduced from the sequence was related to E5 proteins from genital papillomaviruses, to the putative product of the Q300 mouse gene, and to several viral and human growth factors. The data suggest that there may be several cellular counterparts to the viral E5 proteins. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,FREDERICK,MD 21701. RP KAHN, T (reprint author), DEUTSCH KREBSFORSCHUNGSZENTRUM,NEUENHEIMER FELD 242,W-6900 HEIDELBERG,GERMANY. RI Gissmann, Lutz/H-4688-2011 FU NCI NIH HHS [N01-CO-74101] NR 52 TC 9 Z9 9 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PY 1992 VL 6 IS 2 BP 88 EP 99 DI 10.1002/mc.2940060204 PG 12 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA JP796 UT WOS:A1992JP79600003 PM 1326990 ER PT J AU NAKATSUKASA, H EVARTS, RP BURT, RK NAGY, P THORGEIRSSON, SS AF NAKATSUKASA, H EVARTS, RP BURT, RK NAGY, P THORGEIRSSON, SS TI CELLULAR-PATTERN OF MULTIDRUG-RESISTANCE GENE-EXPRESSION DURING CHEMICAL HEPATOCARCINOGENESIS IN THE RAT SO MOLECULAR CARCINOGENESIS LA English DT Note DE MULTIDRUG RESISTANCE; HEPATOCARCINOGENESIS; INSITU HYBRIDIZATION; OVAL CELLS; GLUTATHIONE TRANSFERASE ID PRODUCT P-GLYCOPROTEIN; LIVER EPITHELIAL-CELLS; CYTO-TOXIC CHEMICALS; S-TRANSFERASE-P; V-H-RAS; HEPATOCELLULAR CARCINOMAS; OVEREXPRESSION; NODULES; MDR-1; CYTOCHROME-P-450 AB Increased expression of multidrug-resistance (mdr) gene transcripts and of the encoded protein, P-glycoprotein, is found in many types of tumors. The biological significance of mdr overexpression during the stepwise process of neoplastic development, however, is not well understood. To assess the possible significance of mdr overexpression in carcinogenesis, we examined the cellular distributions of both mdr gene transcripts and P-glycoprotein during hepatocarcinogenesis induced in rats by the Solt-Farber protocol and then compared them to the distributions of the placental form of glutathione S-transferase (GST-P), a known marker of preneoplastic and neoplastic lesions in the liver. In situ hybridization and immunohistochemical techniques were employed. Neither mdr transcripts nor P-glycoprotein was expressed in oval cells that appeared early in the carcinogenic process. GST-P was strongly expressed in the early focal lesions, whereas the levels of mdr transcripts and P-glycoprotein expressed were low and heterogeneous. Expression of mdr transcripts and P-glycoprotein was increased and became more uniform in hyperplastic nodules and carcinomas, although considerable heterogeneity of expression was still found, particularly at the nodular stage. These data suggest that increased expression of mdr is associated with later stages of neoplastic development in the liver. Furthermore, that no chemical treatment of the animals was employed when the expression of mdr was increasing in the preneoplastic and neoplastic lesions suggests that the enhanced mdr expression is intrinsic to the carcinogenic process. RP NAKATSUKASA, H (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BLDG 37,ROOM 3C28,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 28 TC 23 Z9 23 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PY 1992 VL 6 IS 3 BP 190 EP 198 DI 10.1002/mc.2940060304 PG 9 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA KA057 UT WOS:A1992KA05700003 PM 1359897 ER PT J AU BERNSTEIN, LR BRAVO, R COLBURN, NH AF BERNSTEIN, LR BRAVO, R COLBURN, NH TI 12-O-TETRADECANOYLPHORBOL-13-ACETATE INDUCED LEVELS OF AP-1 PROTEINS - A 46-KDA PROTEIN IMMUNOPRECIPITATED BY ANTI-FRA-1 AND INDUCED IN PROMOTION-RESISTANT BUT NOT PROMOTION-SENSITIVE JB6 CELLS SO MOLECULAR CARCINOGENESIS LA English DT Article DE JUN; TUMOR PROMOTER; FOS-RELATED ANTIGEN ID CHICKEN-EMBRYO FIBROBLASTS; TRANSCRIPTION FACTOR AP-1; OSTEO-SARCOMA VIRUS; C-JUN; FOS PROTEINS; DNA-BINDING; GLUCOCORTICOID RECEPTOR; RETINOIC ACID; CELLULAR-TRANSFORMATION; NEGATIVE REGULATION AB Neoplastic transformation and transcriptional activation by activator protein-1 (AP-1) complex are stimulated by tumor-promoting agents in promotion-sensitive (P+) but not promotion-resistant (P-) mouse epidermal JB6 cells in culture. This implicates AP-1 as a specific regulator of signal transduction pathways in the promotion phase of neoplastic transformation. We therefore hypothesized that the defective P- responsiveness may be due to limiting levels of AP-1 protein components in those cells. In this investigation, steady-state levels of AP-1 protein components were measured by immunoprecipitating proteins from 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated P+ and P-cells to discern what may limit the AP-1 response. Whereas the AP-1 proteins junB, junD, and fosB did not show differential basal or TPA-inducible levels in P+ and P- cells, a 46-kDa species precipitated by anti-fra-1 antibody was TPA-inducible in P- cells but not in P+ cells, and c-jun protein was present at higher levels in TPA-treated and untreated P+ cells than in P- cells. These data raise the possibility that the 46-kDa fra-1-related protein may be a negative modulator of AP-1 activity and suggest that elevated levels of this 46-kDa species and limiting levels of c-jun may significantly impair AP-1 function or transformation response in P- cells or both. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,DEPT MOLEC BIOL,PRINCETON,NJ. NR 63 TC 29 Z9 29 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. PY 1992 VL 6 IS 3 BP 221 EP 229 DI 10.1002/mc.2940060308 PG 9 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA KA057 UT WOS:A1992KA05700007 PM 1445622 ER PT J AU YUSPA, SH AF YUSPA, SH TI A CHANGE AT THE HELM SO MOLECULAR CARCINOGENESIS LA English DT Editorial Material RP YUSPA, SH (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PY 1992 VL 6 IS 4 BP 231 EP 231 DI 10.1002/mc.2940060402 PG 1 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA KE903 UT WOS:A1992KE90300001 ER PT J AU ANNAB, LA DONG, JT FUTREAL, PA SATOH, H OSHIMURA, M BARRETT, JC AF ANNAB, LA DONG, JT FUTREAL, PA SATOH, H OSHIMURA, M BARRETT, JC TI GROWTH AND TRANSFORMATION SUPPRESSOR GENES FOR BHK SYRIAN-HAMSTER CELLS ON HUMAN CHROMOSOME-1 AND CHROMOSOME-11 SO MOLECULAR CARCINOGENESIS LA English DT Article DE TUMOR SUPPRESSOR GENES; ANTIONCOGENES; CHEMICAL CARCINOGENESIS; ANCHORAGE-INDEPENDENT GROWTH; CELL TRANSFORMATION ID V-HA-RAS; CHEMICAL CARCINOGENS; SHORT ARM; HETEROZYGOSITY; TUMORS; TUMORIGENICITY; MUTATION; CANCER AB To map putative tumor suppressor genes for the near-diploid baby hamster kidney fibrosarcoma cell line BHK, we transferred five different normal human chromosomes (1, 3, 7, 11, and 12) into these tumor cells by microcell-mediated chromosome transfer. Transfer of human chromosome 1 into BHK cells resulted in suppression of cell growth both on plastic and in soft agar, indicating that chromosome 1 has a generalized effect on cell growth and thereby suppresses anchorage-independent growth. Selection against cells with an intact chromosome 1 was observed. In contrast, the introduction of chromosome 11 into BHK cells resulted in suppression of anchorage independence but not growth on plastic. Most chromosome-11 growth-suppressed BHK hybrids retained intact copies of human chromosome 11. Tumorigenic derivatives of chromosome 11 hybrids had lost this chromosome. Transfer of human chromosome 3, 7, or 12 into BHK cells did not correlate with growth suppression of BHK cells on plastic or in soft agar. Thus, we conclude that genes that suppress BHK-cell growth in general or in agar reside on human chromosomes 1 and 11, respectively. C1 TOTTORI UNIV,YONAGO,TOTTORI 683,JAPAN. RP ANNAB, LA (reprint author), NIEHS,MOLEC CARCINOGENESIS LAB,MD C4-06,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 35 TC 8 Z9 8 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. PY 1992 VL 6 IS 4 BP 280 EP 288 DI 10.1002/mc.2940060410 PG 9 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA KE903 UT WOS:A1992KE90300009 PM 1485918 ER PT J AU EVARTS, RP NAKATSUKASA, H MARSDEN, ER HU, ZY THORGEIRSSON, SS AF EVARTS, RP NAKATSUKASA, H MARSDEN, ER HU, ZY THORGEIRSSON, SS TI EXPRESSION OF TRANSFORMING GROWTH FACTOR-ALPHA IN REGENERATING LIVER AND DURING HEPATIC DIFFERENTIATION SO MOLECULAR CARCINOGENESIS LA English DT Article DE LIVER; TGF-ALPHA; REGENERATION; DIFFERENTIATION ID MESSENGER-RNA; RAT-LIVER; TGF-ALPHA; DEVELOPMENTAL EXPRESSION; INSITU HYBRIDIZATION; TRANSGENIC MICE; CELLS; BETA; OVEREXPRESSION; HEPATOCYTES AB Both the level of expression and cellular distribution of transcripts for transforming growth factor-alpha (TGF-alpha) were studied in adult rat liver after partial hepatectomy and during hepatic differentiation in fetal, neonatal, and adult livers by northern blot analysis and in situ hybridization. A marked increase in the expression of TGF-alpha was observed in neonatal livers and in adult livers after partial hepatectomy and during hepatic regeneration following modification of the Solt-Farber protocol. Quantitation of silver grains after in situ hybridization with a TGF-alpha riboprobe revealed a sixfold to eightfold increase in fetal and neonatal hepatocytes. Moreover, the expression of TGF-alpha in the liver 3 wk after birth was still fourfold higher than that of the adult quiescent liver. Both proliferating oval cells and basophilic foci of hepatocytes generated by modification of the Solt-Farber protocol were positive for TGF-alpha transcripts. The level of TGF-alpha transcripts was sixfold higher in the basophilic foci than in the surrounding liver. High concentrations of TGF-alpha transcripts were observed in the oval cells that lined pseudoducts and in the transitional cells proliferating within the ducts. The combination of in situ hybridization and immunocytochemistry using cell-specific antibodies revealed the presence of TGF-alpha transcripts in both oval cells and in perisinusoidal stellate cells. The observation that TGF-alpha transcripts were found both in primitive liver epithelial cells and perisinusoidal stellate cells suggests that this growth factor, in addition to its mitogenic action, may also have other important functions in the liver. RP EVARTS, RP (reprint author), NCI,DIV CANC ETIOL,EXPTL CARCINOGENESIS LAB,BLDG 37,ROOM 3C28,BETHESDA,MD 20892, USA. NR 31 TC 116 Z9 118 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PY 1992 VL 5 IS 1 BP 25 EP 31 DI 10.1002/mc.2940050107 PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA HG124 UT WOS:A1992HG12400005 PM 1543539 ER PT J AU STEIGERWALT, RW RUNDHAUG, JE NETTESHEIM, P AF STEIGERWALT, RW RUNDHAUG, JE NETTESHEIM, P TI TRANSFORMED RAT TRACHEAL EPITHELIAL-CELLS EXHIBIT ALTERATIONS IN TRANSFORMING GROWTH-FACTOR-BETA SECRETION AND RESPONSIVENESS SO MOLECULAR CARCINOGENESIS LA English DT Article DE TGF-BETA SECRETION; TGF-BETA RESPONSIVENESS; NEOPLASTIC PROGRESSION; NEGATIVE GROWTH REGULATION ID ACCOMPANIES VIRAL TRANSFORMATION; SERUM-FREE MEDIUM; TGF-BETA; NEOPLASTIC PROGRESSION; MESSENGER-RNA; FACTOR RECEPTORS; CARCINOMA-CELLS; CELLULAR GROWTH; POSSIBLE ROLES; CANCER CELLS AB The purpose of our studies was to define abnormalities in the transforming growth factor-beta (TGF-beta) system of transformed rat tracheal epithelial (RTE) cells that might cause their abnormal growth behavior. We found that many, but not all, of the transformed cell lines were hyporesponsive or unresponsive to the growth inhibitory effects of TGF-beta-1. Scatchard and receptor cross-linking analyses indicated that loss of TGF-beta-1 responsiveness of transformed cells was probably not due to changes in receptor number or affinity, or to changes in expression of the three TGF-beta-binding protein subtypes. Transformed cells were found to secrete far less TGF-beta-like activity (< 1/10) than primary cells. Cultured normal and transformed RTE cells expressed three TGF-beta-1 transcripts of 2.5, 1.9, and 1.4 kb. In contrast, rat kidney tissue, a rat embryo fibroblast cell line, and a rat liver cell line expressed only the typical 2.5-kb mRNA transcript commonly reported in the literature. In spite of the marked differences in TGF-beta secretion between normal and transformed cells, their levels of TGF-beta-1 mRNA expression were similar. This suggests a change in the posttranscriptional regulation of TGF-beta-1 expression. TGF-beta-2 message was not detected in either normal or transformed RTE cells in culture. These findings are consistent with the hypothesis that the abnormal growth behavior of transformed RTE cells is at least in part due to disturbances of the TGF-beta system. C1 NIEHS,PULM PATHOBIOL LAB,POB 12233,MD D2-01,RES TRIANGLE PK,NC 27709. NR 62 TC 14 Z9 14 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. PY 1992 VL 5 IS 1 BP 32 EP 40 DI 10.1002/mc.2940050108 PG 9 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA HG124 UT WOS:A1992HG12400006 PM 1311932 ER PT J AU BENARI, ET BERNSTEIN, LR COLBURN, NH AF BENARI, ET BERNSTEIN, LR COLBURN, NH TI DIFFERENTIAL C-JUN EXPRESSION IN RESPONSE TO TUMOR PROMOTERS IN JB6 CELLS SENSITIVE OR RESISTANT TO NEOPLASTIC TRANSFORMATION SO MOLECULAR CARCINOGENESIS LA English DT Article DE AP-1; C-JUN; C-FOS; PHORBOL ESTERS; EPIDERMAL GROWTH FACTOR ID EPIDERMAL GROWTH-FACTOR; PROTEIN KINASE-C; TRANSCRIPTION FACTOR AP-1; EMBRYONAL CARCINOMA-CELLS; RAT FIBROBLASTS; MESSENGER-RNA; 12-O-TETRADECANOYL PHORBOL-13-ACETATE; ELECTROPHORETIC TRANSFER; POLYACRYLAMIDE GELS; ONCOGENE FAMILY AB The activity of AP-1, a trans-acting transcription factor, is stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA) and epidermal growth factor (EGF) in promotion-sensitive (P+) but not in promotion-resistant (P-) JB6 mouse epidermal cell lines. TPA and EGF also promote neoplastic transformation only in P+ cells. Thus, it has been proposed that AP-1-dependent gene expression is involved in determining sensitivity to tumor promotion. This paper explores the possible basis for the differential inducibility of AP-1 activity in P+ and P- JB6 cells, focusing in particular on the regulation of expression of the components of the AP-1 complex at the mRNA level. The expression of jun and fos gene family members, which make up the AP-1 complex, can be stimulated by serum and a number of growth factors, including EGF, and by TPA. Therefore, the possibility that differential expression of one or more forms of jun or fos contributes to the differential AP-1 activity was considered. The data presented here demonstrate both similarities and differences in the basal and TPA- or EGF-induced levels of fos and jun family members between P+ and P cells. The most striking observation was that the overall TPA- and EGF-induced levels of jun but not fos expression were higher in P+ cells. This suggests that tumor promoter-regulated c-jun expression may contribute to the differential AP-1 activation observed in these cells and may be important in determining sensitivity to promotion of neoplastic transformation. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,CELL BIOL SECT,BLDG 560,RM 21-89,FREDERICK,MD 21702. NR 75 TC 47 Z9 47 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. PY 1992 VL 5 IS 1 BP 62 EP 74 DI 10.1002/mc.2940050111 PG 13 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA HG124 UT WOS:A1992HG12400009 PM 1543542 ER PT J AU BOYLAN, JF SHIH, TY FISHER, PB ZIMMER, SG AF BOYLAN, JF SHIH, TY FISHER, PB ZIMMER, SG TI INDUCTION AND PROGRESSION OF THE TRANSFORMED PHENOTYPE IN CLONED RAT EMBRYO FIBROBLAST CELLS - STUDIES EMPLOYING TYPE-5 ADENOVIRUS AND WILD-TYPE AND MUTANT HA-RAS ONCOGENES SO MOLECULAR CARCINOGENESIS LA English DT Article DE ADENOVIRUS-5 TRANSFORMING GENES; HA-RAS MUTANT GENES; TUMORIGENESIS; METASTASIS; CLONED RAT EMBRYO FIBROBLASTS ID NIH 3T3 CELLS; ANCHORAGE-INDEPENDENT GROWTH; GTPASE ACTIVATING PROTEIN; SACCHAROMYCES-CEREVISIAE; E1A GENE; METASTATIC PHENOTYPE; TUMOR PROMOTERS; NIH/3T3 CELLS; NUDE-MICE; MUTATIONS AB Transformation of cloned rat embryo fibroblast (CREF) cells with the wild-type 5 adenovirus (wtAd5) transforming genes E1A and E1B (which extend from 0 to 11.2 map units) results in morphologically transformed cells that exhibit an increased saturation density in monolayer culture and display an anchorage-independent phenotype. WtAd5-transformed CREF (wtAd5 CREF) cells do not, however, induce tumors when injected subcutaneously into athymic nude mice or syngeneic Fischer rats. We have analyzed the effect of the ras oncogene and site-specific mutants in the ras oncogene that result in p21 proteins with altered biochemical properties on the oncogenic and metastatic properties of singly (ras) and doubly (ras + wtAd5) transformed CREF cells. Transformants expressing the wild-type ras p21 protein and ras mutants producing p21 proteins that retained GTP-binding properties grew in agar, induced tumors in nude mice and syngeneic rats, and metastasized to the lungs of rats when injected into their tail veins. In contrast, cells transformed with the ras mutant 116K (which contains a mutation at residue 116 that produces a Lys instead of an Asn and does not bind GTP or induce CREF cells to grow in agar) did not become morphologically transformed and were not oncogenic when injected subcutaneously into either nude mice or Fischer rats; further, such cells were not metastatic when injected into the tail veins of Fischer rats. When the wild-type ras or the ras mutants, including 116K, were expressed in nontumorigenic E1A-plus-E1B-expressing wtAd5 CREF cells, transformed cells induced tumors in both types of animals. The CREF cells doubly transformed with 116K + wtAd5, unlike transformants containing the wild-type ras and the other ras mutants that still retained GTP binding, were still unable to induce lung metastases. In addition, 116K + wtAd5-transformed CREF cells also did not display any alterations in morphology distinguishable from wtAd5 CREF cells and were not able to grow in agar with increased efficiency. These results indicate that the loss of GTP-binding ability by this mutant p21 ras protein eliminated the ability of these proteins to induce an oncogenic phenotype in an immortal but normal CREF cell line. However, the mutant ras could cooperate with wtAd5 transforming genes in transformed CREF cells to make these cells progress to an oncogenic (but not metastatic) phenotype. C1 UNIV KENTUCKY,MED CTR,DEPT MED MICROBIOL & IMMUNOL,800 ROSE ST,LEXINGTON,KY 40536. NCI,MOLEC VIROL LAB,FREDERICK,MD 21701. COLUMBIA UNIV COLL PHYS & SURG,DEPT NEUROSURG,NEW YORK,NY 10032. COLUMBIA UNIV COLL PHYS & SURG,DEPT PATHOL,NEW YORK,NY 10032. COLUMBIA UNIV COLL PHYS & SURG,DEPT UROL,NEW YORK,NY 10032. FU NCI NIH HHS [CA43208, CA35675, CA33434] NR 50 TC 9 Z9 9 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. PY 1992 VL 5 IS 2 BP 118 EP 128 DI 10.1002/mc.2940050207 PG 11 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA HN038 UT WOS:A1992HN03800006 PM 1554410 ER PT J AU HIGINBOTHAM, KG RICE, JM PERANTONI, AO AF HIGINBOTHAM, KG RICE, JM PERANTONI, AO TI ACTIVATING POINT MUTATION IN KI-RAS CODON-63 IN A CHEMICALLY-INDUCED RAT RENAL TUMOR SO MOLECULAR CARCINOGENESIS LA English DT Article DE POLYMERASE CHAIN REACTION; ONCOGENE; CHEMICAL CARCINOGENESIS; KIDNEY ID CENTRAL TRANSFORMING REGION; ONCOGENE ACTIVATION; P21; CARCINOGENESIS; PROTEINS; GENE; TUMORIGENESIS; MUTAGENESIS; CARCINOMAS; INITIATION AB Renal mesenchymal tumors induced in F344 rats with methyl(methoxymethyl)nitrosamine (DMN-OMe) have previously been shown by our laboratory to contain transforming Ki-ras sequences, activated most commonly by a variety of codon 12 mutations. Further sequence analysis of one DMN-OMe-induced tumor with transforming Ki-ras sequences detected by NIH 3T3 transfection assay but with no mutation in codon 12 detected by selective oligonucleotide hybridization has now revealed an activating point mutation in codon 63. The observed GAG --> AAG transition in codon 63, which replaces glutamic acid with lysine, was the only detectable mutation in exon 1 and 2 hotspot regions of Ki-ras in this tumor. The same mutation was also detected in Ki-ras sequences derived from first- and second-cycle transformants in NIH 3T3 transfection assays. Although random mutagenesis studies of cloned Ha-ras sequences by Fasano et al. (Proc Natl Acad Sci USA 81:40008-4012, 1984) had already indicated that GAG --> AAG mutations in codon 63 of ras are transforming, this is the first demonstration of the natural occurrence of this particular activating mutation in a tumor. C1 NCI,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21701. UNIV COLORADO,SCH MED,DEPT PATHOL,DENVER,CO 80202. NR 27 TC 10 Z9 10 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 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PY 1992 VL 5 IS 2 BP 136 EP 139 DI 10.1002/mc.2940050209 PG 4 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA HN038 UT WOS:A1992HN03800008 PM 1554412 ER PT J AU BOFFA, LC MARIANI, MR CARPANETO, EM AF BOFFA, LC MARIANI, MR CARPANETO, EM TI EFFECTS OF N-METHYL-N-NITROSOUREA ON TRANSCRIPTIONALLY ACTIVE AND INACTIVE NUCLEOSOMES - MACROMOLECULAR DAMAGE AND DNA-REPAIR SO MOLECULAR CARCINOGENESIS LA English DT Note DE ALKYLATION; GENOTOXICITY; CHROMATIN; MACROMOLECULE; GENES ID CHEMICAL CARCINOGENS; ALKYLATING-AGENTS; GENE; CELLS; SEQUENCES AB We previously reported a separation, on an organomercurial column, of transcriptionally inactive nucleosomes (class 1) from those containing active gene sequences (classes 2 and 3). In this paper, we analyzed nucleosomal damage caused by exposure of HeLa S3 cells in suspension culture to the directly alkylating carcinogen N-methyl-N-nitrosourea (MNU). The extent and site of methylation induced by the compound in nucleosomal DNA and RNA were determined by cell incubation in the presence of [H-3]MNU. The highest amount of damage was detected in DNA of class 3 nucleosomes, while RNA alkylation was comparable in all nucleosomal classes. Cellular capacity for repair of MNU-induced DNA strand breaks (estimated after a short pulse with [H-3]thymidine) was found to be higher in active nucleosomal fractions (classes 2 and 3) than in the inactive fraction (class 1). Our data support the postulate that chromatin primary structure plays a role in modulating carcinogen damage to chromosomal macromolecules and in DNA strand breakage and repair mechanisms. Some of these initial steps are believed to be critical in the process of carcinogenesis. RP BOFFA, LC (reprint author), NATL CANC INST,IST,DEPT CHEM CARCINOGENESIS,VIALE BENEDETTO XV 10,I-16132 GENOA,ITALY. NR 27 TC 11 Z9 11 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PY 1992 VL 5 IS 3 BP 174 EP 177 DI 10.1002/mc.2940050303 PG 4 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA HU971 UT WOS:A1992HU97100002 PM 1375028 ER PT J AU RISINGER, JI DENT, GA IGNARTROWBRIDGE, D MCLACHLAN, JA TSAO, MS SENTERMAN, M BOYD, J AF RISINGER, JI DENT, GA IGNARTROWBRIDGE, D MCLACHLAN, JA TSAO, MS SENTERMAN, M BOYD, J TI P53 GENE-MUTATIONS IN HUMAN ENDOMETRIAL CARCINOMA SO MOLECULAR CARCINOGENESIS LA English DT Article DE TUMOR SUPPRESSOR GENE; GYNECOLOGIC MALIGNANCY; POLYMERASE CHAIN REACTION; POINT MUTATION ID K-RAS; NEOPLASMS; CANCER AB Although carcinoma of the uterine endometrium is the most frequently diagnosed malignancy of the female reproductive tract, the molecular genetic features of this tumor have yet to be described in significant detail. Since mutations of the p53 tumor suppressor gene are the single most common genetic alteration found in human malignancies, we examined the hypothesis that p53 mutations occur in human endometrial carcinoma. Sequencing analysis of exons 5-8 revealed point mutations in 3 of 21 (14%) tumors; one mutation was an unusual single-base insertion at codons 176-177, resulting in a premature stop codon, whereas the other two were CGG-->TGG transitions at codon 248. Two of these tumors showed reduction to homozygosity at the p53 allele, but one tumor apparently retained heterozygosity. These data indicate that p53 mutations occur in human endometrial carcinoma, although relatively infrequently, and that loss of the normal p53 allele does not necessarily occur with point mutation of the p53 gene in this tumor type. C1 NIEHS,MOLEC CARCINOGENESIS LAB,POB 12233,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,SCH MED,DEPT PATHOL,CHAPEL HILL,NC 27514. MONTREAL GEN HOSP,DEPT PATHOL,MONTREAL H3G 1A4,QUEBEC,CANADA. MONTREAL GEN HOSP,DEPT OBSTET & GYNECOL,MONTREAL H3G 1A4,QUEBEC,CANADA. NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. NR 19 TC 77 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 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PY 1992 VL 5 IS 4 BP 250 EP 253 DI 10.1002/mc.2940050403 PG 4 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA JB221 UT WOS:A1992JB22100001 PM 1497800 ER PT J AU EBERT, R WISEMAN, RW BARRETT, JC REISS, E ROLLICH, G SCHIFFMANN, D AF EBERT, R WISEMAN, RW BARRETT, JC REISS, E ROLLICH, G SCHIFFMANN, D TI CHARACTERIZATION OF THE SYRIAN-HAMSTER C-HA-RAS GENE AND INTRON-D-EXON TRANSCRIPT SO MOLECULAR CARCINOGENESIS LA English DT Article DE CHEMICAL CARCINOGENESIS; HA-RAS; NEGATIVE CONTROL OF GENE EXPRESSION; PROTOONCOGENE; SYRIAN HAMSTER ID MURINE SARCOMA-VIRUS; NUCLEOTIDE-SEQUENCE; GOLDEN-HAMSTER; ONCOGENE; CANCER; MODEL AB The coding sequences as well as 5'- and 3'-flanking sequences of the Syrian hamster c-Ha-ras gene were deduced from cDNA clones derived from embryo fibroblast cell lines. Sequences of introns B, C, and D were obtained from genomic DNA after amplification by the polymerase chain reaction. Sequence comparisons with rat, mouse, and human c-Ha-ras genes revealed a high degree of homology. One of 12 cDNA clones contained intron-D-exon (IDX) sequences due to alternative splicing that would encode a p19 Ha-ras gene product. Conservation between species suggests a functional role for the IDX, possibly as a negative control of p21 Ha-ras expression. C1 NIEHS,MOLEC CARCINOGENESIS LAB,MD D2-04,POB 12233,RES TRIANGLE PK,NC 27709. UNIV WURZBURG,INST PHARMACOL & TOXICOL,W-8700 WURZBURG,GERMANY. NR 47 TC 10 Z9 10 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 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PY 1992 VL 5 IS 4 BP 254 EP 258 DI 10.1002/mc.2940050404 PG 5 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA JB221 UT WOS:A1992JB22100002 PM 1497801 ER PT J AU DLUGOSZ, AA MISCHAK, H MUSHINSKI, JF YUSPA, SH AF DLUGOSZ, AA MISCHAK, H MUSHINSKI, JF YUSPA, SH TI TRANSCRIPTS ENCODING PROTEIN KINASE-C-ALPHA, KINASE-C-DELTA, KINASE-C, KINASE-C-ZETA, AND KINASE-C-ETA ARE EXPRESSED IN BASAL AND DIFFERENTIATING MOUSE KERATINOCYTES INVITRO AND EXHIBIT QUANTITATIVE CHANGES IN NEOPLASTIC-CELLS SO MOLECULAR CARCINOGENESIS LA English DT Article DE PKC ISOZYMES; KERATINOCYTES; NEOPLASIA; RAS; CALCIUM ID CALCIUM CONCENTRATIONS INVITRO; ESTER TUMOR PROMOTERS; EPIDERMAL-CELLS; PHORBOL ESTER; RAS ONCOGENE; SKIN TUMORS; RESISTANT; BINDING; FAMILY; LINES AB The protein kinase C (PKC) family of phospholipid-dependent serine-threonine kinases has been implicated in keratinocyte differentiation and neoplastic transformation. To determine if Ca2+-mediated keratinocyte differentiation is associated with changes in PKC isozyme gene expression, RNA was isolated from primary mouse keratinocytes grown in medium with 0.05, 0.12, or 1.4 mM Ca2+. Based on northern blot analysis, primary keratinocytes expressed mRNA encoding PKC-alpha, -delta, -epsilon, -zeta, and -eta, but not PKC-beta or -gamma. Relatively little change was detected in the level of these transcripts in cells induced to differentiate by exposure to elevated extracellular Ca2+. Interestingly, the PKC-zeta transcripts detected in RNA isolated from keratinocytes were approximately 200 nucleotides longer than those from mouse brain, suggesting the existence of an alternative form of this isozyme. An early change in benign neoplastic transformation of keratinocytes is the inability to differentiate in response to Ca2+ or the PKC activator 12-O-tetradecanoylphorbol-13-acetate, which is consistent with altered PKC function in these cells. The PKC isozyme mRNA profile was examined in two benign neoplastic keratinocyte cell lines, 308 and SP-1, which contain an activating mutation of the c-Ha-ras gene. Like normal keratinocytes, 308 and SP-1 cells expressed mRNA encoding PKC-alpha, -delta, -epsilon, -zeta, and -eta. However, the abundance of PKC-zeta transcripts in both cell lines was reduced by 74-89% when compared with normal keratinocytes at similar Ca2+ levels. In addition, SP-1 but not 308 cells exhibited a sevenfold increase in PKC-eta mRNA when cultured in medium with 1.4 mM Ca2+. To address whether these changes were related to the presence of an activated ras gene, RNA was isolated from primary keratinocytes transduced to a benign neoplastic phenotype with the v-Ha-ras oncogene. As with normal, 308, and SP-1 cells, v-Ha-ras keratinocytes expressed mRNA encoding PKC-alpha, -delta, -epsilon, -zeta, and -eta. The level of PKC-zeta transcripts was similar in normal and v-Ha-ras keratinocytes, indicating that reduction of this mRNA in both 308 and SP-1 cells was not a direct result of ras activation. As in SP-1 cells, PKC-eta in v-Ha-ras keratinocytes was responsive to extracellular Ca2+, with a four-fold increase in transcript abundance in 0.12 mM Ca2+ medium relative to 0.05 mM Ca2+ medium. These findings illustrate the complexity of the PKC-signal transduction pathway in cultured mouse keratinocytes and indicate that the level of certain PKC isozyme transcripts is modulated during the neoplastic process. C1 NCI,GENET LAB,BETHESDA,MD 20892. RP DLUGOSZ, AA (reprint author), NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BLDG 37,ROOM 3B25,BETHESDA,MD 20892, USA. RI Mischak, Harald/E-8685-2011 NR 48 TC 113 Z9 113 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 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PY 1992 VL 5 IS 4 BP 286 EP 292 DI 10.1002/mc.2940050409 PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA JB221 UT WOS:A1992JB22100007 PM 1379814 ER PT J AU HUBER, BE RICHARDS, CA MARTIN, JL WIRTH, PJ AF HUBER, BE RICHARDS, CA MARTIN, JL WIRTH, PJ TI ALTERATIONS IN TUMOR ANGIOGENESIS ASSOCIATED WITH STABLE EXPRESSION OF THE HIV TAT GENE SO MOLECULAR CARCINOGENESIS LA English DT Article DE CAT ASSAYS; XGPRT; MYCOPHENOLIC ACID; 2-DIMENSIONAL GELS; TUMORIGENICITY ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; TRANS-ACTIVATOR GENE; KAPOSIS SARCOMA-CELLS; RAT-LIVER; RESPONSIVE REGION; HTLV-III; T-CELLS; PROTEIN; RNA AB Recent evidence suggests that the human immunodeficiency virus type 1 (HIV) trans-activator gene (tat) has transforming properties and may be a causative factor in the development of certain types of cancers, in particular Kaposi's sarcoma (i.e., Vogel J. et al. Nature 335:606-611, 1988). To help elucidate the potential role or roles of the HIV tat gene in neoplastic transformation, cell lines were constructed that constitutively express a functional tat gene product. HeLa cells were coelectroporated with two plasmids, one containing the HIV tat gene in an expression cassette and another containing the dominant selectable marker gene xanthine guanine phosphoribosyltransferase (XGPRT). After XGPRT selection, single-cell clones that expressed a functional tat protein were identified by measuring chloramphenicol acetyltransferase (CAT) activity after electroporating a plasmid containing the CAT gene transcriptionally controlled by HIV trans-activation-responsive region (tar). Phenotypic alterations resulting from the expression of tat were then determined. Control cells and tat-expressing cells grew at similar rates in culture. However, when grown as tumors in nude mice, tat-expressing cells produced a lower percentage of tumors, and the tumors that were produced either regressed, stopped growing, or grew at a very reduced rate compared with cells not expressing tat. These differences may have resulted from a tat-associated reduction in neovascularization in the tumors. A comparison of total cellular proteins by two-dimensional polyacrylamide gel electrophoresis indicated only one reproducible alteration in a polypeptide of approximately 44 kDa and pl of approximately 6.2 associated with tat expression. These cells may be very useful in future in vitro and in vivo studies designed to examine the effects of HIV tat on endothelial and vascular smooth-muscle cells and the role of tat in the etiology of Kaposi's sarcoma. C1 WELLCOME RES LABS,DEPT VIROL,RES TRIANGLE PK,NC 27709. NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. RP HUBER, BE (reprint author), WELLCOME RES LABS,DIV CELL BIOL,3030 CORNWALLIS RD,RES TRIANGLE PK,NC 27709, USA. NR 42 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. PY 1992 VL 5 IS 4 BP 293 EP 300 DI 10.1002/mc.2940050410 PG 8 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA JB221 UT WOS:A1992JB22100008 PM 1379815 ER PT J AU KALIMI, GH HAMPTON, LL TROSKO, JE THORGEIRSSON, SS HUGGETT, AC AF KALIMI, GH HAMPTON, LL TROSKO, JE THORGEIRSSON, SS HUGGETT, AC TI HOMOLOGOUS AND HETEROLOGOUS GAP-JUNCTIONAL INTERCELLULAR COMMUNICATION IN V-RAF-TRANSDUCED, V-MYC-TRANSDUCED, AND V-RAF/V-MYC-TRANSDUCED RAT-LIVER EPITHELIAL-CELL LINES SO MOLECULAR CARCINOGENESIS LA English DT Article DE CONNEXIN-43; CONNEXIN-26; TUMORIGENESIS; ONCOGENE; HEPATOCARCINOGENESIS ID TEMPERATURE-SENSITIVE MUTANT; ROUS-SARCOMA VIRUS; SRC GENE-PRODUCT; BALB/C 3T3 CELLS; POTENTIAL ROLE; VIRAL ONCOGENES; TUMOR PROMOTER; HA-RAS; GROWTH; INHIBITION AB We examined gap-junctional intercellular communication (GJIC) in a series of normal and v-raf-, v-myc-, and v-raf/v-myc-transduced rat liver epithelial (RLE) cell lines using the scrape loading-dye transfer and fluorescence-recovery-after-photobleaching (FRAP) assays. Whereas the normal RLE cell line, the control helper virus-transduced cell line, and the v-myc-transduced cell line all showed excellent GJIC, the v-raf-transduced cell lines displayed decreasing levels of GJIC associated with their increasing tumorigenicity. The v-raf/v-myc-transformed cell lines showed the lowest levels of GJIC and were also the most tumorigenic. Heterologous GJIC of these oncogene-transduced cell lines was also compared with that in the normal RLE cells. A modified FRAP assay, using fluorescent-microbead labeling to identify the oncogene-transduced cell from surrounding normal cells, was used to quantify the heterologous GJIC. The v-raf/v-myc-transformed RLE cells had no heterologous communication with the normal RLE cells, whereas v-raf- and v-myc-transduced cell lines maintained heterologous GJIC. Northern analysis showed that connexin 43 was the only gap-junction protein message expressed in these cell lines; connexin 32 and connexin 26 were not expressed. The levels of connexin 43 mRNA expression were relatively unchanged in all cell lines, suggesting that the reduction in GJIC was primarily at the posttranslational level. These findings suggest that reduction of homologous GJIC in v-raf- and v-raf/v-myc-transformed RLE cells is linked to their tumorigenic potential. Furthermore, the loss of heterologous GJIC, which we observed only in the v-raf/v-myc-transformed cells, might release such cells from the growth-regulating effects of surrounding normal cells, possibly contributing to their enhanced tumorigenic potential. C1 MICHIGAN STATE UNIV,DEPT PEDIAT & HUMAN DEV,B240 LIFE SCI BLDG,E LANSING,MI 48824. NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA21104] NR 51 TC 45 Z9 45 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. PY 1992 VL 5 IS 4 BP 301 EP 310 DI 10.1002/mc.2940050411 PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA JB221 UT WOS:A1992JB22100009 PM 1379816 ER PT J AU MACARTHUR, LH CLARKE, MF WESTIN, EH AF MACARTHUR, LH CLARKE, MF WESTIN, EH TI MALIGNANT TRANSFORMATION OF NIH 3T3 FIBROBLASTS BY HUMAN C-SIS IS DEPENDENT UPON THE LEVEL OF ONCOGENE EXPRESSION SO MOLECULAR CARCINOGENESIS LA English DT Article DE PLATELET-DERIVED GROWTH FACTOR; ONCOGENE; GROWTH FACTOR; TUMORIGENICITY ID GROWTH-FACTOR; CELL-LINES; MYELOGENOUS LEUKEMIA; GENE; MYC; DNA; PROTEINS; PDGF; NITROCELLULOSE; TRANSCRIPTS AB High-level expression of the c-sis oncogene, which encodes the beta-chain of platelet-derived growth factor, transforms immortalized rodent fibroblasts in vitro to a malignant phenotype. c-sis gene expression has been demonstrated in a variety of human tumors, although generally at levels much lower than those shown to transform cells in vitro. We examined the effect of lower levels of c-sis expression on the phenotype of NIH 3T3 fibroblasts. Clones with various levels of c-sis expression were generated by transfecting NIH 3T3 cells with a plasmid that expressed the human c-sis cDNA and the TN5 neomycin-resistance gene. G418-resistant clones, which expressed the c-sis cDNA, were selected and characterized. Alterations in the phenotype of the clones that expressed c-sis ranged from increased growth in soft agar to malignant tumor formation in nude and syngeneic mice. Increased levels of c-sis cDNA expression correlated with the acquisition of features of transformation in a dose-dependent manner and altered the cellular phenotype in a manner consistent with the progression of cells towards malignancy. These data support a model in which low levels of sis gene expression in tumors contribute to the acquisition of some features of transformation but require complementation by other genes or factors to produce a fully malignant phenotype. C1 UNIV MICHIGAN,DEPT MED,ANN ARBOR,MI 48109. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT MED,DIV HEMATOL ONCOL,RICHMOND,VA 23298. RP MACARTHUR, LH (reprint author), NIMH,CELL BIOL LAB,ROCKVILLE,MD 20857, USA. NR 40 TC 10 Z9 10 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. PY 1992 VL 5 IS 4 BP 311 EP 319 DI 10.1002/mc.2940050412 PG 9 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA JB221 UT WOS:A1992JB22100010 PM 1323300 ER PT J AU MCMASTER, MT TENG, CT DEY, SK ANDREWS, GK AF MCMASTER, MT TENG, CT DEY, SK ANDREWS, GK TI LACTOFERRIN IN THE MOUSE UTERUS - ANALYSES OF THE PREIMPLANTATION PERIOD AND REGULATION BY OVARIAN-STEROIDS SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID METALLOTHIONEIN GENE-EXPRESSION; NEUTROPHIL CHEMOTACTIC FACTOR; REPRODUCTIVE-TRACT; RAT UTERUS; LOCALIZATION; RECEPTOR; LACTOTRANSFERRIN; RELEASE; INVITRO; GROWTH AB Uterine expression of lactoferrin (LF) during the preimplantation period and its regulation by the ovarian steroids estradiol (E2) and/or progesterone (P4) in ovariectomized adult mice were examined. Immunoblot detection of LF in uterine cell lysates demonstrated the presence of this protein from days 1-8 of pregnancy [day 1 (D1) = day of vaginal plug]. Immunoprecipitation of S-35 pulse-labeled uterine proteins showed that the relative rate of LF synthesis was high on D1, but below the level of detection by D4. Immunolocalization of LF in uterine sections showed intense luminal and glandular epithelial staining on D1 and D2, and progressively decreased staining through D4. Immunoreactive protein was also detected in cells, primarily concentrated in the stroma. The relative number of these cells was greatest on D1 and decreased progressively to a low number by D4. These cells were morphologically similar to neutrophils, which are known to contain LF protein, but little or no LF mRNA. Northern blotting showed that uterine LF mRNA levels were very high on D1 and D2 of pregnancy and decreased to low, but detectable, levels by D4. In situ hybridization to uterine sections showed that LF mRNA was highly abundant only in glandular and luminal epithelial cells, and followed the same pattern as immunolocalization on D1-D4 in epithelial cells. These results document two sources of LF in the preimplantation mouse uterus: neutrophils and epithelial cells. The synthesis of LF in the uterus reflects the abundance of epithelial LF mRNA, which is high on the first 2 days of pregnancy. Neutrophils that contain LF are also abundant in the uterine stroma during this time. E2 and/or P4 regulation of uterine LF was examined. LF mRNA was rapidly induced by E2 in ovariectomized adult mice, and this mRNA was localized exclusively to epithelial cells. P4 had little effect on uterine LF mRNA levels, but antagonized the prolonged induction of this gene by E2. E2 induced the accumulation of immunoreactive LF in uterine epithelial cells and the appearance of numerous immunopositive neutrophils distributed throughout the uterine stroma. P4 also antagonized these effects. Thus, E2 regulates LF gene expression in uterine epithelial cells and causes the recruitment of neutrophils into the uterus. These results suggest that LF may play an important role in early pregnancy and that uterine LF gene expression is regulated by a balance between estrogen and P4. C1 UNIV KANSAS, MED CTR, RALPH L SMITH RES CTR, DEPT BIOCHEM & MOLEC BIOL, KANSAS CITY, KS 66103 USA. UNIV KANSAS, MED CTR, RALPH L SMITH RES CTR, DEPT OBSTET GYNECOL & PHYSIOL, KANSAS CITY, KS 66103 USA. NIEHS, REPROD & DEV TOXICOL LAB, RES TRIANGLE PK, NC 27709 USA. FU NICHD NIH HHS [HD-12304]; NIEHS NIH HHS [ES-04725] NR 43 TC 75 Z9 76 U1 3 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JAN PY 1992 VL 6 IS 1 BP 101 EP 111 DI 10.1210/me.6.1.101 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HH373 UT WOS:A1992HH37300012 PM 1738363 ER PT B AU HARRIS, CC AF HARRIS, CC BE Harris, CC Hirohashi, S Ito, N Pitot, HC Sugimura, T Terada, M Yokota, J TI KEYNOTE LECTURE - MOLECULAR-BASIS OF MULTISTAGE CARCINOGENESIS SO MULTISTAGE CARCINOGENESIS SE PRINCESS TAKAMATSU SYMPOSIA LA English DT Proceedings Paper CT 22nd International Symposium of the Princess-Takamatsu-Cancer-Research-Fund : Multistage Carcinogenesis CY NOV 19-21, 1991 CL TOKYO, JAPAN SP PRINCESS TAKAMATSU CANC RES FUND RP HARRIS, CC (reprint author), NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU JAPAN SCIENTIFIC SOC PRESS PI TOKYO PA 2-10 HONGO, 6-CHOME, BUNKYO-KU, TOKYO 113, JAPAN BN 4-7622-6717-1 J9 PRINCESS TAKAMATSU S PY 1992 VL 22 BP 3 EP 19 PG 17 WC Oncology SC Oncology GA BZ39Q UT WOS:A1992BZ39Q00001 ER PT B AU NETTESHEIM, P FERRIOLA, PC ROBERTSON, AT IWANAGA, T STEIGERWALT, R RUNDHAUG, JE AF NETTESHEIM, P FERRIOLA, PC ROBERTSON, AT IWANAGA, T STEIGERWALT, R RUNDHAUG, JE BE Harris, CC Hirohashi, S Ito, N Pitot, HC Sugimura, T Terada, M Yokota, J TI ABNORMALITIES OF GROWTH-FACTOR SYSTEMS IN TRANSFORMED AIRWAY EPITHELIAL-CELLS SO MULTISTAGE CARCINOGENESIS SE PRINCESS TAKAMATSU SYMPOSIA LA English DT Proceedings Paper CT 22nd International Symposium of the Princess-Takamatsu-Cancer-Research-Fund : Multistage Carcinogenesis CY NOV 19-21, 1991 CL TOKYO, JAPAN SP PRINCESS TAKAMATSU CANC RES FUND RP NETTESHEIM, P (reprint author), NIEHS,PULM PATHOBIOL LAB,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JAPAN SCIENTIFIC SOC PRESS PI TOKYO PA 2-10 HONGO, 6-CHOME, BUNKYO-KU, TOKYO 113, JAPAN BN 4-7622-6717-1 J9 PRINCESS TAKAMATSU S PY 1992 VL 22 BP 171 EP 181 PG 11 WC Oncology SC Oncology GA BZ39Q UT WOS:A1992BZ39Q00015 ER PT B AU HOWLEY, PM MUNGER, K ROMANCZUK, H SCHEFFNER, M HUIBREGTSE, JM AF HOWLEY, PM MUNGER, K ROMANCZUK, H SCHEFFNER, M HUIBREGTSE, JM BE Harris, CC Hirohashi, S Ito, N Pitot, HC Sugimura, T Terada, M Yokota, J TI CELLULAR TARGETS OF THE ONCOPROTEINS ENCODED BY THE CANCER-ASSOCIATED HUMAN PAPILLOMAVIRUSES SO MULTISTAGE CARCINOGENESIS SE PRINCESS TAKAMATSU SYMPOSIA LA English DT Proceedings Paper CT 22nd International Symposium of the Princess-Takamatsu-Cancer-Research-Fund : Multistage Carcinogenesis CY NOV 19-21, 1991 CL TOKYO, JAPAN SP PRINCESS TAKAMATSU CANC RES FUND RP HOWLEY, PM (reprint author), NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892, USA. RI Scheffner, Martin/K-2940-2012 OI Scheffner, Martin/0000-0003-2229-0128 NR 0 TC 4 Z9 4 U1 0 U2 0 PU JAPAN SCIENTIFIC SOC PRESS PI TOKYO PA 2-10 HONGO, 6-CHOME, BUNKYO-KU, TOKYO 113, JAPAN BN 4-7622-6717-1 J9 PRINCESS TAKAMATSU S PY 1992 VL 22 BP 239 EP 248 PG 10 WC Oncology SC Oncology GA BZ39Q UT WOS:A1992BZ39Q00021 ER PT B AU CASTRONOVO, V STETLERSTEVENSON, WG SOBEL, ME LIOTTA, LA AF CASTRONOVO, V STETLERSTEVENSON, WG SOBEL, ME LIOTTA, LA BE Harris, CC Hirohashi, S Ito, N Pitot, HC Sugimura, T Terada, M Yokota, J TI MOLECULAR INHIBITION OF CANCER CELL INVASION AND METASTASIS SO MULTISTAGE CARCINOGENESIS SE PRINCESS TAKAMATSU SYMPOSIA LA English DT Proceedings Paper CT 22nd International Symposium of the Princess-Takamatsu-Cancer-Research-Fund : Multistage Carcinogenesis CY NOV 19-21, 1991 CL TOKYO, JAPAN SP PRINCESS TAKAMATSU CANC RES FUND RP CASTRONOVO, V (reprint author), NCI,PATHOL LAB,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JAPAN SCIENTIFIC SOC PRESS PI TOKYO PA 2-10 HONGO, 6-CHOME, BUNKYO-KU, TOKYO 113, JAPAN BN 4-7622-6717-1 J9 PRINCESS TAKAMATSU S PY 1992 VL 22 BP 319 EP 337 PG 19 WC Oncology SC Oncology GA BZ39Q UT WOS:A1992BZ39Q00028 ER PT J AU MCFEE, AF TICE, RR SHELBY, MD AF MCFEE, AF TICE, RR SHELBY, MD TI INVIVO CYTOGENETIC ACTIVITY OF DIPHENYLHYDANTOIN IN MICE SO MUTATION RESEARCH LA English DT Article DE DIPHENYLHYDANTOIN; ANTICONVULSIVE; CHROMOSOME ABERRATIONS; SCE; MICRONUCLEI ID BONE-MARROW CELLS; POLYCHROMATIC ERYTHROCYTES; ANTICONVULSANT DRUGS; PERIPHERAL-BLOOD; PHENYTOIN; CHROMOSOMES; INDUCTION; KINETICS; FETAL; TIME AB Diphenylhydantoin was tested in vivo in mice using a variety of cytogenetic endpoints to evaluate its genotoxicity. Injected doses of 125, 250 and 500 mg/kg failed to increase the number of chromosome aberrations in marrow cells at 17 h post-treatment, and 37.5, 75 and 150 mg/kg doses were likewise ineffective at 36 h. SCEs were significantly increased by doses of 125 mg/kg (but not 250 mg) after 23 h and modestly, in relation to dose, at 42 h. No increase in the number of micronuclei among marrow PCEs was seen following single i.v. injections ranging from 0.1 to 20 mg/kg. Three daily i.p. injections of doses up to 70 mg/kg also failed to increase the number of micronuclei in either marrow or peripheral blood PCEs. Some cytotoxic effect was evident following relatively high doses. C1 INTEGRATED LAB SYST INC,RES TRIANGLE PK,NC. NIEHS,RES TRIANGLE PK,NC 27709. RP MCFEE, AF (reprint author), OAK RIDGE ASSOCIATED UNIV,DIV MED SCI,POB 117,OAK RIDGE,TN 37831, USA. FU NCI NIH HHS [Y01-CP-10207]; NIEHS NIH HHS [Y01-ES-20100, N0 1-ES-85209] NR 31 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD JAN PY 1992 VL 278 IS 1 BP 61 EP 68 DI 10.1016/0165-1218(92)90286-9 PG 8 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA GV880 UT WOS:A1992GV88000008 PM 1370120 ER PT J AU LEWTAS, J CLAXTON, LD ROSENKRANZ, HS SCHUETZLE, D SHELBY, M MATSUSHITA, H WURGLER, FE ZIMMERMANN, FK LOFROTH, G MAY, WE KREWSKI, D MATSUSHIMA, T OHNISHI, Y GOPALAN, HNG SARIN, R BECKING, GC AF LEWTAS, J CLAXTON, LD ROSENKRANZ, HS SCHUETZLE, D SHELBY, M MATSUSHITA, H WURGLER, FE ZIMMERMANN, FK LOFROTH, G MAY, WE KREWSKI, D MATSUSHIMA, T OHNISHI, Y GOPALAN, HNG SARIN, R BECKING, GC TI DESIGN AND IMPLEMENTATION OF A COLLABORATIVE STUDY OF THE MUTAGENICITY OF COMPLEX-MIXTURES IN SALMONELLA-TYPHIMURIUM SO MUTATION RESEARCH LA English DT Article DE SALMONELLA-TYPHIMURIUM; COMPLEX MIXTURES; BACTERIAL MUTAGENICITY; AMES TEST; ENVIRONMENTAL MIXTURES; COLLABORATIVE STUDY; INTERLABORATORY VARIABILITY AB In 1987, the International Programme on Chemical Safety (IPCS) in collaboration with the U.S. Environmental Protection Agency (U.S. EPA) and the U.S. National Institute of Standards and Technology (U.S. NIST) initiated an international collaborative study of the mutagenicity of complex environmental mixtures in the Ames Salmonella typhimurium mutation assay. The objectives of this study were: (1) to estimate the inter- and intra-laboratory variability associated with the extraction of mixtures for bioassay, (2) to estimate the inter- and intra-laboratory variability associated with the Salmonella typhimurium bioassay when applied to complex mixtures, and (3) to determine whether standard reference complex mixtures would be useful in mutagenicity studies and to evaluate whether reference or certified mutagenicity values determined from this collaborative study should be reported. The complex mixtures used in this study were selected from standard reference materials (SRMs) which had previously been issued by the U.S. NIST as SRM 1597 (coal tar), SRM 1649 (diesel particulate matter) and SRM 1650 (urban air particulate matter) with certified values for polycyclic aromatic hydrocarbons. These SRM complex mixtures are available to scientists as reference standards for analytical chemistry research and are under consideration as SRMs for mutagenicity studies of complex environmental mixtures. This paper briefly describes the final study design, protocol, selection of the complex mixtures, and implementation of this international study. C1 NATL INST PUBL HLTH,MINATO KU,TOKYO 108,JAPAN. NORD SCH PUBL HLTH,GOTHENBURG,SWEDEN. NATL INST STAND & TECHNOL,GAITHERSBURG,MD 20899. NATL ENVIRONM ENGN RES INST,NAGPUR,INDIA. WHO,INT PROGRAMME CHEM SAFETY,INTERREG RES UNIT,RES TRIANGLE PK,NC 27709. UNIV PITTSBURGH,DEPT ENVIRONM & OCCUPAT HLTH,PITTSBURGH,PA 15261. FORD MOTOR CO,SCI RES LAB,DEARBORN,MI 48121. NIEHS,RES TRIANGLE PK,NC 27709. UNIV ZURICH,SWISS FED INST TECHNOL,CH-8603 SCHWERZENBACH,SWITZERLAND. TH DARMSTADT,INST MIKROBIOL,W-6100 DARMSTADT,GERMANY. HLTH & WELF CANADA,ENVIRONM HLTH DIRECTORATE,OTTAWA K1A 0L2,ONTARIO,CANADA. UNIV TOKYO,INST MED SCI,DEPT MOLEC ONCOL,TOKYO 113,JAPAN. UNIV TOKUSHIMA,TOKUSHIMA 770,JAPAN. UNIV NAIROBI,DEPT BOT,NAIROBI,KENYA. RP LEWTAS, J (reprint author), US EPA,DIV GENET TOXICOL,HLTH EFFECTS RES LAB,GENET BIOASSAY BRANCH,MD 68,RES TRIANGLE PK,NC 27711, USA. OI Claxton, Larry/0000-0001-7455-1583 NR 14 TC 22 Z9 22 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD JAN-MAR PY 1992 VL 276 IS 1-2 BP 3 EP 9 DI 10.1016/0165-1110(92)90051-A PG 7 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA GW949 UT WOS:A1992GW94900002 PM 1370107 ER PT J AU LUZAR, MA AF LUZAR, MA TI PERITONITIS PREVENTION IN CONTINUOUS AMBULATORY PERITONEAL-DIALYSIS SO NEPHROLOGIE LA French DT Article DE CONTINUOUS AMBULATORY PERITONEAL DIALYSIS; DISCONNECT SYSTEMS; EXIT-SITE INFECTION; NASAL CARRIER; PERITONITIS; TREATMENT; Y-SET AB Although peritonitis remains the major cause of morbidity in CAPD, peritonitis rates are declining in European and other countries. This article reviews approaches that are both decisive and promising concerning the prevention of peritonitis in CAPD. Clinical results with both reusable and single-use Y sets are discussed. These systems appear to have a significant impact on the reduction of intraluminal contamination, particularly Staphylococcus epidermidis. The importance of the flush-before-fill technique is reviewed in the context of the new disposable Y sets. In vitro studies confirm that 100 mls of fresh dialysate flushed from the new bag to the drainage bag at the appropriate time during the exchange can eliminate microorganisms that do not possess adherence factors, providing long periods of incubation are not encountered. Future prevention measures for the reduction of Staphylococcus aureus peritonitis are discussed in light of evidence identifying pre-CAPD nasal carriers as high risk patients for subsequent exit-site infection and S. aureus peritonitis. These measures include methods such as the application of antibiotics such as mupirocin to the anterior nares before and during CAPD. The roles of intraperitoneal IgG therapY and staphylococcal vaccination as additional therapeutic approaches to infection control in peritoneal dialysis are also discussed. RP LUZAR, MA (reprint author), NIAID,DIV AIDS,6003 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MEDECINE ET HYGIENE PI GENEVA 4 PA 78 AVE ROSERALE, 1211 GENEVA 4, SWITZERLAND SN 0250-4960 J9 NEPHROLOGIE JI Nephrologie PY 1992 VL 13 IS 4 BP 171 EP 177 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA JQ142 UT WOS:A1992JQ14200006 PM 1407258 ER PT J AU YAMAGAMI, K JOSEPH, JA ROTH, GS AF YAMAGAMI, K JOSEPH, JA ROTH, GS TI MUSCARINIC RECEPTOR CONCENTRATIONS AND DOPAMINE RELEASE IN AGED RAT STRIATA SO NEUROBIOLOGY OF AGING LA English DT Article DE MUSCARINIC RECEPTORS; AGING; DOPAMINE RELEASE; STRIATUM ID NUCLEUS BASALIS MAGNOCELLULARIS; MEMORY DEFICITS; CHOLINE-ACETYLTRANSFERASE; PHYSOSTIGMINE; BRAIN; HIPPOCAMPUS; SUBTYPES; LESIONS; BINDING AB The extent to which age-related decreases in muscarinic enhancement of K+-evoked dopamine release (K+-ERDA) from perifused striatal slices is dependent upon the loss of striatal muscarinic receptors (mAChR) was determined. Both K+-ERDA and mAChR (M1, M2) concentrations were assessed from the same animals (3, 5-7 and 24-27 months). Results indicated associated decreases of 70% in oxotremorine-enhanced K+-ERDA and 36% in B(max) (H-3-QNB) (3 and 24-27 months groups). Decrease of mAChR B(max) was not the result of membrane sequestration. Although both the concentrations of M1 and M2 muscarinic receptor subtypes decline with age, only the M2 receptor decline was correlated with the age-related decreases in muscarinic enhancement of K+-ERDA (r = .71, p < 0.001). Results suggest that age-related decreases in mAChR concentrations as being partially responsible for deficits in muscarinic enhancement of K+-evoked release of DA. C1 NIA,GERONTOL RES CTR,FRANCIS SCOTT KEY MED CTR,BALTIMORE,MD 21224. RI Yamagami, Keiji/E-9500-2012 NR 37 TC 6 Z9 6 U1 1 U2 1 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 JAN-FEB PY 1992 VL 13 IS 1 BP 51 EP 56 DI 10.1016/0197-4580(92)90008-L PG 6 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA GY126 UT WOS:A1992GY12600007 PM 1542381 ER PT B AU HERKENHAM, M AF HERKENHAM, M BE KALIVAS, PW SAMSON, HH TI CANNABINOID RECEPTOR LOCALIZATION IN BRAIN - RELATIONSHIP TO MOTOR AND REWARD SYSTEMS SO NEUROBIOLOGY OF DRUG AND ALCOHOL ADDICTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Proceedings Paper CT CONF ON THE NEUROBIOLOGY OF DRUG AND ALCOHOL ADDICTION CY JUL 23-26, 1991 CL SPOKANE, WA SP NEW YORK ACAD SCI, UNIV WASHINGTON, WASHINGTON STATE UNIV, NIAAA RP HERKENHAM, M (reprint author), NIMH,FUNCT NEUROANAT SECT,BLDG 36,ROOM 2D-15,BETHESDA,MD 20892, USA. OI Herkenham, Miles/0000-0003-2228-4238 NR 0 TC 71 Z9 73 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA NEW YORK BN 0-89766-711-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1992 VL 654 BP 19 EP 32 DI 10.1111/j.1749-6632.1992.tb25953.x PG 14 WC Substance Abuse; Neurosciences SC Substance Abuse; Neurosciences & Neurology GA BW41T UT WOS:A1992BW41T00004 PM 1385932 ER PT B AU BOJA, JW CLINE, EJ CARROLL, FI LEWIN, AH PHILIP, A DANNALS, R WONG, D SCHEFFEL, U KUHAR, MJ AF BOJA, JW CLINE, EJ CARROLL, FI LEWIN, AH PHILIP, A DANNALS, R WONG, D SCHEFFEL, U KUHAR, MJ BE KALIVAS, PW SAMSON, HH TI HIGH POTENCY COCAINE ANALOGS - NEUROCHEMICAL, IMAGING, AND BEHAVIORAL-STUDIES SO NEUROBIOLOGY OF DRUG AND ALCOHOL ADDICTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Proceedings Paper CT CONF ON THE NEUROBIOLOGY OF DRUG AND ALCOHOL ADDICTION CY JUL 23-26, 1991 CL SPOKANE, WA SP NEW YORK ACAD SCI, UNIV WASHINGTON, WASHINGTON STATE UNIV, NIAAA RP BOJA, JW (reprint author), NIDA,ADDICT RES CTR,NEUROSCI BRANCH,POB 5180,BALTIMORE,MD 21224, USA. NR 0 TC 28 Z9 28 U1 2 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA NEW YORK BN 0-89766-711-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1992 VL 654 BP 282 EP 291 DI 10.1111/j.1749-6632.1992.tb25974.x PG 10 WC Substance Abuse; Neurosciences SC Substance Abuse; Neurosciences & Neurology GA BW41T UT WOS:A1992BW41T00025 PM 1632587 ER PT B AU POST, RM WEISS, SRB FONTANA, D PERT, A AF POST, RM WEISS, SRB FONTANA, D PERT, A BE KALIVAS, PW SAMSON, HH TI CONDITIONED SENSITIZATION TO THE PSYCHOMOTOR STIMULANT COCAINE SO NEUROBIOLOGY OF DRUG AND ALCOHOL ADDICTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Proceedings Paper CT CONF ON THE NEUROBIOLOGY OF DRUG AND ALCOHOL ADDICTION CY JUL 23-26, 1991 CL SPOKANE, WA SP NEW YORK ACAD SCI, UNIV WASHINGTON, WASHINGTON STATE UNIV, NIAAA RP POST, RM (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 69 Z9 70 U1 2 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA NEW YORK BN 0-89766-711-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1992 VL 654 BP 386 EP 399 DI 10.1111/j.1749-6632.1992.tb25983.x PG 14 WC Substance Abuse; Neurosciences SC Substance Abuse; Neurosciences & Neurology GA BW41T UT WOS:A1992BW41T00034 PM 1632592 ER PT B AU COLOMBO, G GRANT, KA AF COLOMBO, G GRANT, KA BE KALIVAS, PW SAMSON, HH TI NMDA RECEPTOR COMPLEX ANTAGONISTS HAVE ETHANOL-LIKE DISCRIMINATIVE STIMULUS EFFECTS SO NEUROBIOLOGY OF DRUG AND ALCOHOL ADDICTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Proceedings Paper CT CONF ON THE NEUROBIOLOGY OF DRUG AND ALCOHOL ADDICTION CY JUL 23-26, 1991 CL SPOKANE, WA SP NEW YORK ACAD SCI, UNIV WASHINGTON, WASHINGTON STATE UNIV, NIAAA RP COLOMBO, G (reprint author), NIAAA,PHYSIOL & PHARMACOL STUDIES LAB,RECEPTOR MECHANISMS SECT,ROCKVILLE,MD 20852, USA. NR 0 TC 23 Z9 23 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA NEW YORK BN 0-89766-711-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1992 VL 654 BP 421 EP 423 DI 10.1111/j.1749-6632.1992.tb25986.x PG 3 WC Substance Abuse; Neurosciences SC Substance Abuse; Neurosciences & Neurology GA BW41T UT WOS:A1992BW41T00037 PM 1385933 ER PT J AU BACHMAN, DL WOLF, PA LINN, R KNOEFEL, JE COBB, J BELANGER, A DAGOSTINO, RB WHITE, LR AF BACHMAN, DL WOLF, PA LINN, R KNOEFEL, JE COBB, J BELANGER, A DAGOSTINO, RB WHITE, LR TI PREVALENCE OF DEMENTIA AND PROBABLE SENILE DEMENTIA OF THE ALZHEIMER TYPE IN THE FRAMINGHAM-STUDY SO NEUROLOGY LA English DT Article ID CLINICAL-DIAGNOSIS; DISEASE; POPULATION; COMMUNITY; DISORDERS; FEATURES; CRITERIA AB We determined the prevalence of dementia and probable senile dementia of the Alzheimer type (SDAT) for biennial Exam 17 of the Framingham cohort (1982/1983). The prevalence of dementia was 30.5/1,000 for men and 48.2/1,000 for women and increased with advancing age. Cases of probable SDAT constituted 55.6% of all dementia cases. The prevalence of SDAT was 11.7/1,000 for men and 30.1/1,000 for women and also increased with advancing age. Prevalence of dementia and probable SDAT were greater for women than men. The female:male ratio of prevalence for cohort members 75 years of age and older was 1.8 for all cases of dementia and 2.8 for cases of probable SDAT. C1 BOSTON UNIV,SCH MED,DEPT NEUROL,80 E CONCORD ST B608,BOSTON,MA 02118. BOSTON UNIV,DEPT MATH,BOSTON,MA 02215. NIA,EPIDEMIOL PROGRAM,BETHESDA,MD 20892. NIA,DEMOG PROGRAM,BETHESDA,MD 20892. NIA,BIOMETRY PROGRAM,BETHESDA,MD 20892. FU NHLBI NIH HHS [N01-HC-38-038]; NIA NIH HHS [1R01-AG-08122-01] NR 28 TC 354 Z9 357 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN PY 1992 VL 42 IS 1 BP 115 EP 119 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA HA895 UT WOS:A1992HA89500021 PM 1734291 ER PT J AU HIGGINS, JJ PATTERSON, MC PAPADOPOULOS, NM BRADY, RO PENTCHEV, PG BARTON, NW AF HIGGINS, JJ PATTERSON, MC PAPADOPOULOS, NM BRADY, RO PENTCHEV, PG BARTON, NW TI HYPOPREBETALIPOPROTEINEMIA, ACANTHOCYTOSIS, RETINITIS-PIGMENTOSA, AND PALLIDAL DEGENERATION (HARP SYNDROME) SO NEUROLOGY LA English DT Article; Proceedings Paper CT 43RD ANNUAL MEETING OF THE AMERICAN ACADEMY OF NEUROLOGY CY APR, 1991 CL BOSTON, MA SP AMER ACAD NEUROL ID HALLERVORDEN-SPATZ SYNDROME; DISEASE; MR; ABNORMALITIES; DISORDERS AB We describe the clinical and laboratory studies of an 11-year-old girl with prominent orofacial dyskinesia, dystonia, and progressive dementia. Investigations revealed hypoprebetalipoproteinemia, acanthocytosis, atypical retinitis pigmentosa, and evidence of iron deposition in the pallidal nuclei. Electroneuromyography and skin and sural nerve biopsies were normal. The "eye-of-the-tiger" sign, used to describe the pallidal nuclei in Hallervorden-Spatz syndrome, was present on T2-weighted MRIs (GE Signa, 1.5 T). Phase-contrast microscopy of whole blood showed 80 to 90% acanthocytes whose morphology was confirmed by electron microscopy. High-resolution lipoprotein electrophoresis demonstrated an absence of the pre-beta fraction. This case differs phenotypically from the previous reports of Hallervorden-Spatz disease with acanthocytosis by the presence of prominent orofacial dyskinesia and abnormal serum lipoproteins. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,BETHESDA,MD 20892. RP HIGGINS, JJ (reprint author), NINCDS,DEV & METAB NEUROL BRANCH,BLDG 10,ROOM 3D03,BETHESDA,MD 20892, USA. OI Patterson, Marc/0000-0002-1116-126X NR 22 TC 40 Z9 40 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN PY 1992 VL 42 IS 1 BP 194 EP 198 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA HA895 UT WOS:A1992HA89500034 PM 1734303 ER PT S AU SOKOLOFF, L AF SOKOLOFF, L BE Yu, ACH Hertz, L Norenberg, MD Sykova, E Waxman, SG TI THE BRAIN AS A CHEMICAL MACHINE SO NEURONAL-ASTROCYTIC INTERACTIONS: IMPLICATIONS FOR NORMAL AND PATHOLOGICAL CNS FUNCTION SE PROGRESS IN BRAIN RESEARCH LA English DT Proceedings Paper CT STANFORD CENTENNIAL SYMP ON NEURONAL-ASTROCYTIC INTERACTIONS CY JUL 10-13, 1991 CL HONG KONG, HONG KONG SP STANFORD UNIV, DEPT PATHOL, AMER MED ASSOC HONG KONG RP SOKOLOFF, L (reprint author), NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892, USA. RI Sykova, Eva/H-2659-2014 NR 0 TC 58 Z9 58 U1 0 U2 2 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA AMSTERDAM SN 0079-6123 BN 0-444-89537-X J9 PROG BRAIN RES PY 1992 VL 94 BP 19 EP 33 PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA BX24B UT WOS:A1992BX24B00002 PM 1337612 ER PT J AU FISHBEIN, DH DAX, E LOZOVSKY, DB JAFFE, JH AF FISHBEIN, DH DAX, E LOZOVSKY, DB JAFFE, JH TI NEUROENDOCRINE RESPONSES TO A GLUCOSE CHALLENGE IN SUBSTANCE USERS WITH HIGH AND LOW-LEVELS OF AGGRESSION, IMPULSIVITY, AND ANTISOCIAL PERSONALITY SO NEUROPSYCHOBIOLOGY LA English DT Article DE GLUCOSE TOLERANCE TEST; ANTISOCIAL PERSONALITY; AGGRESSIVE BEHAVIOR; NEUROENDOCRINE RESPONSE ID REACTIVE HYPOGLYCEMIC TENDENCY; DIAGNOSTIC INTERVIEW SCHEDULE; TOLERANCE TEST; HABITUALLY VIOLENT; MONOAMINE-OXIDASE; INSULIN-SECRETION; ALCOHOLISM; OFFENDERS; PROLACTIN; DISORDERS AB Plasma glucose concentrations, and plasma prolactin and cortisol responses to a 5-hour oral glucose tolerance test (OGTT) in 37 substance abusers, were examined to assess the relationship between varying degrees of antisocial personality, impulsivity, and aggressiveness and measures of endocrine function. Childhood and presenting aggression, impulsivity and antisocial personality features were evaluated by several self-report questionnaires. Those with high scores for psychopathic deviance (MMPI) differed in glucose levels following OGTT from those with low scores. Lower cortisol nadir levels were associated with higher scores on measures of antisocial personality and aggressiveness. Also, prolactin response to glucose was attenuated relative to baseline levels in the more antisocial and aggressive subjects. The results indicate that substance abusers with high levels of self-reported antisocial personality and aggressive behavior have altered neuroendocrine responses to glucose challenge, although there was no evidence of hypoglycemia. No one personality or behavioral trait, as measured by our test battery, more strongly predicted neuroendocrine responses to glucose administration. Thus, our data partially support other reports of altered neuroendocrine responses to stressful challenges in aggressive/antisocial individuals. C1 NIDA,ADDICT RES CTR,BALTIMORE,MD. RP FISHBEIN, DH (reprint author), UNIV BALTIMORE,DEPT CRIMINAL JUSTICE,1420 N CHARLES ST,BALTIMORE,MD 21201, USA. NR 69 TC 13 Z9 13 U1 2 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0302-282X J9 NEUROPSYCHOBIOLOGY JI Neuropsychobiology PY 1992 VL 25 IS 2 BP 106 EP 114 DI 10.1159/000118818 PG 9 WC Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA HW092 UT WOS:A1992HW09200007 PM 1625777 ER PT B AU MAYER, ML BENVENISTE, M PATNEAU, DK VYKLICKY, L AF MAYER, ML BENVENISTE, M PATNEAU, DK VYKLICKY, L BE LANGSTON, JW YOUNG, A TI PHARMACOLOGICAL PROPERTIES OF NMDA RECEPTORS SO NEUROTOXINS AND NEURODEGENERATIVE DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Proceedings Paper CT CONF ON NEUROTOXINS AND THEIR POTENTIAL ROLES IN NEURODEGENERATION CY MAY 06-08, 1991 CL NEW YORK, NY SP NEW YORK ACAD SCI, NINDS, ICI, PHARM GRP, CIBA GEIGY, GLAXO RES LABS, DUPONT CO, FISONS PHARM, HOFFMANN LA ROCHE, JOHNSON & JOHNSON, LILLY RES LABS RP MAYER, ML (reprint author), NICHHD,DEV NEUROBIOL LAB,NEUROPHYSIOL & BIOPHYS SECT,BLDG 36,ROOM 2A21,BETHESDA,MD 20892, USA. RI Vyklicky, Ladislav/C-1851-2012; Mayer, Mark/H-5500-2013 OI Vyklicky, Ladislav/0000-0002-0015-0098; NR 0 TC 28 Z9 29 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA NEW YORK BN 0-89766-696-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1992 VL 648 BP 194 EP 204 DI 10.1111/j.1749-6632.1992.tb24538.x PG 11 WC Neurosciences; Pathology; Toxicology SC Neurosciences & Neurology; Pathology; Toxicology GA BW41P UT WOS:A1992BW41P00023 PM 1386202 ER PT J AU MAHON, KA DAWID, IB AF MAHON, KA DAWID, IB TI DEVELOPMENT SHOWS SOME BACKBONE SO NEW BIOLOGIST LA English DT Article ID NERVOUS-SYSTEM; MOUSE; EXPRESSION; GENE C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. RP MAHON, KA (reprint author), NICHHD,MAMMALIAN GENES & DEV LAB,BETHESDA,MD 20892, USA. NR 13 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4674 J9 NEW BIOL PD JAN PY 1992 VL 4 IS 1 BP 36 EP 41 PG 6 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA HC449 UT WOS:A1992HC44900006 PM 1346970 ER PT J AU ABRAHAM, NG BENZ, EJ KARLSSON, S LUTTON, J CLARK, SC AF ABRAHAM, NG BENZ, EJ KARLSSON, S LUTTON, J CLARK, SC TI THE STEM-CELL MAVENS HAD A BLAST SO NEW BIOLOGIST LA English DT Article C1 YALE UNIV,SCH MED,DEPT HEMATOL,NEW HAVEN,CT 06510. NIH,MOLEC & MED GENET SECT,BETHESDA,MD 20892. GENET INST,CAMBRIDGE,MA. RP ABRAHAM, NG (reprint author), NEW YORK MED COLL,DEPT MED,VALHALLA,NY 10595, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4674 J9 NEW BIOL PD JAN PY 1992 VL 4 IS 1 BP 42 EP 47 PG 6 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA HC449 UT WOS:A1992HC44900007 PM 1346971 ER PT J AU DOBSON, GP VEECH, RL PASSONNEAU, JV KOBAYASHI, K INUBUSHI, T WEHRLI, S NIOKA, S CHANCE, B AF DOBSON, GP VEECH, RL PASSONNEAU, JV KOBAYASHI, K INUBUSHI, T WEHRLI, S NIOKA, S CHANCE, B TI P-31 NMR AND ENZYMATIC ANALYSIS OF CYTOSOLIC PHOSPHOCREATINE, ATP, P(I) AND INTRACELLULAR PH IN THE ISOLATED WORKING PERFUSED RAT-HEART SO NMR IN BIOMEDICINE LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; SATURATION-TRANSFER; CREATINE-KINASE; MUSCLE; ISCHEMIA; SYSTEM; SPECTROSCOPY; METABOLITES; NUCLEOTIDES; EXCHANGE AB Hearts from fed male Wistar rats (200-350 g) were perfused at low and high workloads with P(i)-free Krebs-Henseleit medium containing either 10 mM glucose or 10 mM glucose plus 15 mU/mL insulin. The intracellular pH by P-31 NMR ranged between 6.99 and 7.02 and agreed to within 0.1 pH unit of estimates calculated using enzymatically determined total tissue HCO3-/CO2 contents. At high work, where the tissue contents of phosphocreatine (PCr) and ATP were determined on the same heart as NMR areas (n = 16), the proportionality factors, defined as the P-31 NMR area units divided by the total enzymatically determined tissue content (area units/mu-mol/g dry wt), were 112 +/- 8 for PCr, 99 +/- 4 for gamma-ATP, 138 +/- 9 for alpha-ATP and 100 +/- 4 for beta-ATP. These values were normalized by taking beta-ATP as 200 area units/mu-mol/g dry wt. Since the proportionality factor for PCr and gamma- and beta-ATP were not statistically different (p < 0.05), it was concluded that each was equally visible by P-31 NMR and that no significant breakdown of PCr occurred during freezing or tissue acid extraction procedures. The cytosolic P(i) estimated from NMR in glucose plus insulin perfused hearts at low and high work was 4.92 +/- 0.67 and 6.33 +/- 0.42-mu-mol/g dry wt. Using the near-equilibrium expression of K(CK)/K(G + G) and the metabolite levels in heart extracts, the calculated cytosolic P(i) was 13.08 +/- 1.83 and 16.17 +/- 3.08-mu-mol/g drv wt, respectively. The cytosolic NMR P(i) in the glucose hearts was 8.42 +/- 1.0 and 8.42 +/- 0.75-mu-mol/g drv wt at low and high work and 12.08 +/- 1.58 and 27.20 +/- 4.20-mu-mol/g dry wt from near-equilibrium estimates. The total tissue P(i) measured enzymatically on freeze-clamped hearts ranged from 18.0 to 26.42-mu-mol/g dry wt. The validity of using both the P-31 NMR and the near-equilibrium method for estimating cytosolic P(i) in the heart was discussed. C1 UNIV PENN,DEPT BIOCHEM & BIOPHYS,PHILADELPHIA,PA 19104. RP DOBSON, GP (reprint author), NIAAA,METAB & MOLEC BIOL LAB,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 48 TC 16 Z9 16 U1 0 U2 3 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 JAN-FEB PY 1992 VL 5 IS 1 BP 20 EP 28 DI 10.1002/nbm.1940050105 PG 9 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA HF869 UT WOS:A1992HF86900003 PM 1550706 ER PT J AU RUSS, PL HEGEDUS, L KELLEY, JA BARCHI, JJ MARQUEZ, VE AF RUSS, PL HEGEDUS, L KELLEY, JA BARCHI, JJ MARQUEZ, VE TI THE CONTROLLED STEREOSPECIFIC REDUCTION OF CYCLOPENTENYL CYTOSINE (CPE-C) TO CARBODINE AND ISOCARBODINE SO NUCLEOSIDES & NUCLEOTIDES LA English DT Article AB The preferential cis-addition of hydrogen to either face of the carbocyclic double bond of enantiomerically pure cyclopentenyl cytosine (1) was achieved. The resulting saturated carbocyclic nucleosides carbodine (2) and isocarbodine (3) were evaluated against human influenza virus. Carbodine showed the greater potency against this virus but the activity of isocarbodine was still substantial. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. RI Barchi Jr., Joseph/N-3784-2014 NR 8 TC 15 Z9 15 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0732-8311 J9 NUCLEOS NUCLEOT JI Nucleosides Nucleotides PY 1992 VL 11 IS 2-4 BP 351 EP 363 DI 10.1080/07328319208021709 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HU043 UT WOS:A1992HU04300016 ER PT J AU LIM, BB MARQUEZ, VE DOBYNS, KA COONEY, DA DECLERCQ, E AF LIM, BB MARQUEZ, VE DOBYNS, KA COONEY, DA DECLERCQ, E TI SYNTHESIS AND BIOLOGICAL STUDY OF THE CYCLOPENTENYL CARBOCYCLIC NUCLEOSIDE ANALOG OF 5-AZACYTIDINE SO NUCLEOSIDES & NUCLEOTIDES LA English DT Article ID DNA METHYLATION; 5-AZA-2'-DEOXYCYTIDINE; DIFFERENTIATION; TRIPHOSPHATE; ANTITUMOR; CYTOSINE; CYTIDINE AB Cyclopentenyl cytosine (CPE-C, 3) possesses excellent antitumor and antiviral activity. The synthesis of the analogous cyclopentenyl triazine nucleoside, 5-aza-CPE-C (4), was accomplished by a novel approach that utilized a key 1-cyclopentenyl-4-methylisobiuret intermediate (7) produced from the corresponding cyclopentenylamine 5. 5-Aza-CPE-C was more than six-hundred times less potent than CPE-C both in its capacity to reduce CTP levels as well as in its antitumor and antiviral activity. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. CATHOLIC UNIV LEUVEN,REGA INST MED RES,B-3000 LOUVAIN,BELGIUM. NR 30 TC 7 Z9 7 U1 0 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0732-8311 J9 NUCLEOS NUCLEOT JI Nucleosides Nucleotides PY 1992 VL 11 IS 6 BP 1123 EP 1135 DI 10.1080/07328319208018331 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JA276 UT WOS:A1992JA27600001 ER PT J AU BARCHI, JJ HACES, A MARQUEZ, VE MCCORMACK, JJ AF BARCHI, JJ HACES, A MARQUEZ, VE MCCORMACK, JJ TI INHIBITION OF CYTIDINE DEAMINASE BY DERIVATIVES OF 1-(BETA-D-RIBOFURANOSYL)-DIHYDROPYRIMIDIN-2-ONE (ZEBULARINE) SO NUCLEOSIDES & NUCLEOTIDES LA English DT Article ID NUCLEOSIDES; ANALOGS AB The 2'-deoxy and ara derivatives of 1-beta-(D-ribofuranosyl)-1,2-dihydropyrimidin-2-one (zebularine) were synthesized by improved routes and tested for their inhibitory properties against cytidine deaminase. It was shown that the K(i)'s of both compounds were comparable to that of the parent zebularine in inhibition studies with purified enzyme. In contrast to zebularine, 2'-deoxy and ara zebularine showed only nominal cytotoxicity against MOLT-4 and L1210 cells in vitro. A model compound for the inhibition of deoxycytidylate deaminase, 2'-deoxyzebularine 5'-monophosphate (6), was also prepared. C1 UNIV VERMONT,BURLINGTON,VT 05405. RP BARCHI, JJ (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892, USA. RI Barchi Jr., Joseph/N-3784-2014 NR 23 TC 9 Z9 9 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 SN 0732-8311 J9 NUCLEOS NUCLEOT JI Nucleosides Nucleotides PY 1992 VL 11 IS 10 BP 1781 EP 1793 DI 10.1080/07328319208017823 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KE155 UT WOS:A1992KE15500009 ER PT B AU HAVLIK, RJ AF HAVLIK, RJ BE MUNRO, H SCHLIERF, G TI HEALTH-STATISTICS ON OLDER PERSONS SO NUTRITION OF THE ELDERLY SE NESTLE NUTRITION WORKSHOP SERIES LA English DT Proceedings Paper CT 29TH WORKSHOP ON NUTRITION OF THE ELDERLY CY MAY 22-24, 1991 CL WASHINGTON, DC SP NESTLE NUTR SERV RP HAVLIK, RJ (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,7201 WISCONSIN AVE,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU RAVEN PRESS PI NEW YORK PA NEW YORK BN 0-88167-874-0 J9 NESTLE NUTR WORKS SE PY 1992 VL 29 BP 7 EP 16 PG 10 WC Geriatrics & Gerontology; Nutrition & Dietetics SC Geriatrics & Gerontology; Nutrition & Dietetics GA BV33U UT WOS:A1992BV33U00002 ER PT J AU REDNER, RL LEE, AWM OSAWA, GA NIENHUIS, AW AF REDNER, RL LEE, AWM OSAWA, GA NIENHUIS, AW TI VARIABLE PATTERN OF JUN AND FOS GENE-EXPRESSION IN DIFFERENT HEMATOPOIETIC-CELL LINES DURING INTERLEUKIN 3-INDUCED ENTRY INTO THE CELL-CYCLE SO ONCOGENE LA English DT Article ID FACTOR-I RECEPTOR; LEUCINE ZIPPER DOMAIN; PROTO-ONCOGENE; GROWTH-FACTORS; C-JUN; MONOCYTIC DIFFERENTIATION; PHOSPHATIDYLINOSITOL 3-KINASE; MOUSE FIBROBLASTS; G0/G1 TRANSITION; ANTISENSE RNA AB Jun (c-jun, jun-B and jun-D) and fos (c-fos, fos-B and fra) proteins dimerize to form the family of AP-1 transcriptional activators. If each dimer exhibits unique transactivating properties, then any phenotypic change should show a characteristic pattern of jun and fos expression. To test this hypothesis we have assessed jun and fos RNA expression after stimulation of the factor-dependent cell lines 32D and FDCP1. These hematopoietic progenitor lines become quiescent in G0/G1 after interleukin 3 (IL-3) deprivation, and upon stimulation synchronously enter the cell cycle. 32D cells respond to IL-3 with rapid induction of jun-B and c-fos, followed by induction of jun-D and fra-1, but no rise in c-jun expression. FDCP1 cells show a very different pattern, with induction of c-jun, jun-D and fra-1. To investigate the response of a single cell line to different physiological stimuli we used a 32D subclone engineered to respond to colony stimulating factor 1 (CSF-1). This subclone showed identical induction of jun and fos after stimulation with either CSF-1 or IL-3. The conservation of response of a single cell line, but the disparate patterns demonstrated by different cells, suggest a fundamental difference in both the regulation and function of the fos/jun complexes in these cells. C1 NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. NR 58 TC 10 Z9 10 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN PY 1992 VL 7 IS 1 BP 43 EP 50 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA HC227 UT WOS:A1992HC22700006 PM 1371337 ER PT J AU MEDCALF, EA TAKAHASHI, T CHIBA, I MINNA, J MILNER, J AF MEDCALF, EA TAKAHASHI, T CHIBA, I MINNA, J MILNER, J TI TEMPERATURE-SENSITIVE MUTANTS OF P53 ASSOCIATED WITH HUMAN CARCINOMA OF THE LUNG SO ONCOGENE LA English DT Article ID TUMOR SUPPRESSOR PROTEIN; MONOCLONAL-ANTIBODIES; SIMIAN VIRUS-40; IMMUNOLOGICAL VARIANTS; GENE; TRANSFORMATION; ANTIGEN; CANCER; EXPRESSION; ONCOGENE AB We have compared the effects of specific point mutations on the tertiary and quaternary structure of the human p53 protein. Eight mutants, each derived from primary resected tissues of lung carcinomas, were expressed in vitro under strictly defined conditions, such that the only known variant was the point mutation present in each p53 mRNA. All the mutations were located in highly conserved domains. The tertiary structure of each mutant protein was investigated by reactivity with anti-p53 monoclonal antibodies directed against conformation-dependent epitopes. Quaternary structure was examined by gel filtration. Although all the mutant proteins exhibited abnormal tertiary structures, their quaternary structures appeared similar to wild type, the one exception being p53-tyr135, which contains tyrosine in place of cysteine at residue 135. The conformational phenotype of mutant human p53 was found to be dependent upon (i) the locus of the mutation and (ii) the nature of the amino acid substitution: two different substitutions at residue 273 yielded two mutants with differing structural properties. We have discovered three mutants of human p53 that are temperature sensitive for conformation; one is mutated at codon 273, a 'hotspot' for p53 mutation in human cancer. C1 UNIV CAMBRIDGE,DEPT PATHOL,DIV VIROL,TENNIS COURT RD,CAMBRIDGE CB2 1QP,ENGLAND. USN HOSP,NCI,MED ONCOL BRANCH,BETHESDA,MD 20814. RI Takahashi, Takashi/I-7262-2014 NR 32 TC 37 Z9 37 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN PY 1992 VL 7 IS 1 BP 71 EP 76 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA HC227 UT WOS:A1992HC22700010 PM 1741167 ER PT J AU GIVOL, I GREENHOUSE, JJ HUGHES, SH EWERT, DL AF GIVOL, I GREENHOUSE, JJ HUGHES, SH EWERT, DL TI RETROVIRUSES THAT EXPRESS DIFFERENT RAS MUTANTS CAUSE DIFFERENT TYPES OF TUMORS IN CHICKENS SO ONCOGENE LA English DT Article ID MURINE SARCOMA-VIRUS; TRANSFORMING GENE; DNA; FIBROBLASTS; PROTEINS; PROVIDE; VECTORS; SRC AB We have used replication-competent retroviral vectors to express avian and murine ras genes in cultured chick embryo fibroblasts (CEF) and in chickens. Since the viral vectors are identical, it is possible to compare the oncogenic potential of the ras genes directly. The normal (12 gly) form of chicken c-Ha-ras is not oncogenic in vivo, nor does high-level expression transform CEF. Expression of murine v-ras or modified forms of chicken c-Ha-ras with either lysine or glutamine at position 12 transforms CEF and causes tumors in birds. However, the oncogenic potential of the transforming ras genes is different, the viruses that express the genes with lysine and glutamine at position 12 cause a distinct spectrum of tumors. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,POB B,FREDERICK,MD 21702. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. WISTAR INST,PHILADELPHIA,PA 19104. FU NCI NIH HHS [N01-CO-74101, CA39000] NR 16 TC 8 Z9 8 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN PY 1992 VL 7 IS 1 BP 141 EP 146 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA HC227 UT WOS:A1992HC22700019 PM 1632878 ER PT J AU HEIDARAN, MA MOLLOY, CJ PANGELINAN, M CHOUDHURY, GG WANG, LM FLEMING, TP SAKAGUCHI, AY PIERCE, JH AF HEIDARAN, MA MOLLOY, CJ PANGELINAN, M CHOUDHURY, GG WANG, LM FLEMING, TP SAKAGUCHI, AY PIERCE, JH TI ACTIVATION OF THE COLONY-STIMULATING FACTOR-I RECEPTOR LEADS TO THE RAPID TYROSINE PHOSPHORYLATION OF GTPASE-ACTIVATING PROTEIN AND ACTIVATION OF CELLULAR P21RAS SO ONCOGENE LA English DT Article ID FACTOR-I RECEPTOR; GAP-ASSOCIATED PROTEINS; GROWTH-FACTOR RECEPTORS; PHOSPHOLIPASE-C-GAMMA; PDGF BETA-RECEPTOR; KINASE-ACTIVITY; PHOSPHATIDYLINOSITOL 3-KINASE; CSF-1; TRANSFORMATION; PRODUCT AB We have previously reported that platelet-derived growth factor (PDGF) induced tyrosine phosphorylation of GTPase-activating protein (GAP) in intact quiescent fibroblasts under conditions in which insulin and basic fibroblast growth factor (bFGF) were ineffective (Molloy et al., 1988). In the present study, we have provided evidence that colony-stimulating factor 1 (CSF-1) is capable of inducing tyrosine phosphorylation of GAP and its associated cellular proteins, p62 and p190, in NIH3T3 cells overexpressing the human CSF-1 receptor (CSF-1R). However, the extent of GAP tyrosine phosphorylation induced by CSF-1 was approximately 10% of that induced by PDGF-BB in the NIH3T3 fibroblasts. Despite this significant difference, both PDGF-BB and CSF-1 increased the activation of p21ras, the extent of which correlated well with the mitogenic response induced by each growth factor in these cells. Taken together, our findings provide evidence for a possible role of tyrosine phosphorylation of GAP and GAP-associated phosphoproteins in regulating transduction of CSF-1-induced mitogenic signals through p21ras activation. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. UNIV TEXAS,HLTH SCI CTR,DEPT CELLULAR & STRUCT BIOL,SAN ANTONIO,TX 78284. RI Molloy, Christopher/A-6821-2013 OI Molloy, Christopher/0000-0003-2964-6166 NR 40 TC 34 Z9 34 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN PY 1992 VL 7 IS 1 BP 147 EP 152 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA HC227 UT WOS:A1992HC22700020 PM 1311060 ER PT J AU MITSUDOMI, T STEINBERG, SM NAU, MM CARBONE, D DAMICO, D BODNER, S OIE, HK LINNOILA, RI MULSHINE, JL MINNA, JD GAZDAR, AF AF MITSUDOMI, T STEINBERG, SM NAU, MM CARBONE, D DAMICO, D BODNER, S OIE, HK LINNOILA, RI MULSHINE, JL MINNA, JD GAZDAR, AF TI P53 GENE-MUTATIONS IN NON-SMALL-CELL LUNG-CANCER CELL-LINES AND THEIR CORRELATION WITH THE PRESENCE OF RAS MUTATIONS AND CLINICAL-FEATURES SO ONCOGENE LA English DT Article ID POLYMERASE CHAIN-REACTION; TUMOR SUPPRESSOR GENE; SV40-TRANSFORMED CELLS; POINT MUTATIONS; BREAST-CANCER; MUTANT P53; WILD-TYPE; CARCINOMA; ONCOGENE; TRANSFORMATION AB We screened 77 non-small-cell lung cancer (NSCLC) cell lines for mutations of the p53 gene using a single-strand conformation polymorphism (SSCP) assay. We found that 57 cell lines (74%) had mutations of the p53 gene. Three cell lines had a deletion of the p53 gene. Of the remaining 54 cell lines, 49 cell lines were sequenced and 52 mutations were confirmed. In contrast to previously published p53 mutations in other human tumors, the p53 gene mutations in NSCLC were diverse with regard to the location and nature of the mutations. The region corresponding to codons 144-166, which is outside the evolutionarily conserved regions, was a frequent site of p53 gene mutations in NSCLC. The presence of a p53 gene mutation was not associated with age, sex, histological types, culture site, treatment intent, presence of prior cytotoxic treatment, neuroendocrine differentiation, median culture time or patient survival. The prevalence of p53 mutations in cell lines with ras mutations did not differ from that in cell lines without ras mutations. However, p53 gene mutations in NSCLC cell lines with ras mutations tended to cluster in exon 8, suggesting the presence of a functional domain of the p53 gene relating to interaction with the ras gene. We conclude that p53 and ras mutations are frequent and apparently independent genetic alterations which play different roles in the pathogenesis, progression and prognosis of NSCLC. C1 USN,NCI,MED ONCOL BRANCH,BETHESDA,MD 20889. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20889. UNIV TEXAS,SW MED CTR,SIMMONS CANC CTR,DALLAS,TX 75235. OI Mitsudomi, Tetsuya/0000-0001-9860-8505 NR 65 TC 468 Z9 469 U1 4 U2 12 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN PY 1992 VL 7 IS 1 BP 171 EP 180 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA HC227 UT WOS:A1992HC22700023 PM 1311061 ER PT J AU HIRANO, K SMITH, BM COLBURN, NH AF HIRANO, K SMITH, BM COLBURN, NH TI DIFFERENTIAL INDUCTION OF 15 AND 16 KDA NUCLEAR PROTEINS IN PROMOTION SENSITIVE AND PROMOTION RESISTANT MOUSE JB6 CELLS SO ONCOLOGY RESEARCH LA English DT Article ID EPIDERMAL-CELLS; TUMOR PROMOTERS; MESSENGER-RNA; PHORBOL ESTERS; KINASE-C; GENES; EXPRESSION; TRANSFORMATION; PROGRESSION; PHENOTYPE AB Gene expression relevant to promotion of neoplastic transformation was investigated by measuring proteins differentially synthesized in two mouse epidermal JB6 cell lines sensitive (P+) or resistant (P-) to tumor promoter induced transformation. One dimensional polyacrylamide gel electrophoresis of proteins from cells that had been pulse labeled with S-35-methionine after various times of exposure to the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) revealed two protein bands whose intensity increased after 20-24 hr exposure to TPA. Cell fractionation showed that these proteins of 15 and 16 kDa were localized in the nuclear, not the cytosolic, fraction. Parallel studies With P-32-labeled cells showed no evidence for phosophorylation of these proteins. Comparison of P- with P+ cells showed that the observed induction of p15/16 synthesis at 20 hr was specific for P+ cells, with little evidence for stimulated synthesis in P- cells during a 48 hr period. We thus conclude that the tumor promoter produces a late stimulation in the rate of synthesis of 15 and 16 kDa nuclear proteins preferentially in promotion sensitive cells. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. NR 38 TC 5 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0965-0407 J9 ONCOL RES JI Oncol. Res. PY 1992 VL 4 IS 1 BP 17 EP 21 PG 5 WC Oncology SC Oncology GA HZ099 UT WOS:A1992HZ09900003 PM 1581616 ER PT J AU FRUEHAUF, JP SINHA, BK AF FRUEHAUF, JP SINHA, BK TI SELECTIVE FORMATION OF TUMOR-NECROSIS-FACTOR-ALPHA (TNF) DEGRADATION PRODUCTS CONTRIBUTES TO TNF MEDIATED CYTOTOXICITY SO ONCOLOGY RESEARCH LA English DT Article ID EPIDERMAL GROWTH-FACTOR; MOLECULAR-CLONING; RESISTANT CELLS; FACTOR RECEPTOR; PHASE-I; EXPRESSION; CANCER; BINDING; INTERNALIZATION; DOXORUBICIN AB We compared tumor necrosis factor (TNF) metabolism by wild-type MCF-7 (WT) cells, by 40-fold doxorubicin resistant (40F) breast cancer cells and by PC3 and LNCaP prostate cancer cell lines. MCF-7 WT and LNCaP cell lines were sensitive to TNF cytotoxicity and both lines produced two major intracellular TNF degradation products of 15 kDa and 5.5 kDa. The MCF-7 40F and the PC3 cell lines were resistant to TNF and produced multiple TNF degradation products with molecular weights lower than 15 kDa. Both the breast and prostate lines showed TNF receptor crosslinking patterns consistent with a molecular weight of 55 kDa. The breast and LNCaP lines expressed TNF receptors with an apparent dissociation constant (K(d)) of 0.4 to 0.6 nM, while the TNF resistant line had a K(d) of 2 nM. Similar receptor numbers per cell were found for all cell types (4.000 to 8,000/cell), and comparable levels of TNF internalization were noted. TNF-conditioned medium from the TNF-sensitive cell types was cytotoxic toward both the TNF-sensitive and TNF-resistant lines, and the toxicity was significantly blocked by an anti-TNF monoclonal antibody. Hydrophobic interaction column HPLC fractionation of the TNF-degradation products produced by MCF-7 WT and LNCaP cells revealed that the trimeric, monomeric, and 5.5 kDa fractions possessed the greatest in vitro antitumor activity. These findings suggest that a TNF degradation product, produced selectively by TNF-sensitive cells, may contribute to the antitumor action of TNF. C1 NCI,CLIN PHARMACOL BRANCH,BIOCHEM & MOLEC PHARMACOL SECT,BETHESDA,MD 20892. NR 37 TC 10 Z9 10 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0965-0407 J9 ONCOL RES JI Oncol. Res. PY 1992 VL 4 IS 3 BP 91 EP 101 PG 11 WC Oncology SC Oncology GA JC712 UT WOS:A1992JC71200002 PM 1319775 ER PT J AU MIMNAUGH, EG MONTI, E SEBERS, S STETLERSTEVENSON, M SINHA, BK AF MIMNAUGH, EG MONTI, E SEBERS, S STETLERSTEVENSON, M SINHA, BK TI SYNERGISTIC ANTIPROLIFERATIVE EFFECTS OF THE COMBINATION OF INTERLEUKIN-1-ALPHA AND DOXORUBICIN AGAINST HUMAN-MELANOMA CELLS SO ONCOLOGY RESEARCH LA English DT Article ID TUMOR-NECROSIS-FACTOR; ANTITUMOR-ACTIVITY; DRUG-RESISTANCE; FREE-RADICALS; B-CELLS; T-CELLS; RECEPTOR; BIOLOGY; INTERNALIZATION; BINDING AB We have investigated the antiproliferative effects of recombinant human interleukin-la (IL-1) combined with the cytotoxic antitumor drug doxorubicin against A375 human melanoma IL-1-sensitive (C6) and IL-1-resistant (C5) clonal cell lines. Growth inhibition was assessed by the MTT assay, and C5 cells were 10-fold less sensitive to IL-1 than the C6 cells, but both cell lines were equally sensitive to doxorubicin. Synergistic antitumor activity between die two agents was evaluated by median effects/combination index analysis, and IL-1 and doxorubicin were strongly synergistic over a broad range of drug concentrations. The strongest synergism occurred when C6 cells were exposed to IL-1 prior to doxorubicin, and when C5 cells were pretreated with doxorubicin for 6 hr prior to IL-1 additions. An examination of various ratios of the two agents revealed a maximum 20-fold potentiation of doxorubicin, and a 30-fold potentiation of IL-1 median dose values in the combination compared to the median dose values obtained with doxorubicin or IL-1 alone. Doxorubicin treatment enhanced the binding and internalization of [I-125]IL-1 after 24 and 48 hr at 37-degrees-C, but IL-1 binding to cells incubated on ice was increased only marginally by doxorubicin pretreatment. Treatment of C6 cells with IL-1 for 24 hr did not alter the cellular accumulation of doxorubicin. A recombinant protein IL-1 receptor antagonist that binds to both the 80 kDa type I and the 65 kDa type II IL-1 receptors, blocked the cytostatic effects of IL-1 and abrogated the synergism with doxorubicin. In cells synchronized following release from aphidicolin block, doxorubicin caused a G2+ M accumulation, IL-1 alone had no effect, and the combination of both agents resulted in a G2 + M block similar in magnitude to that caused by doxorubicin alone. These results provide preclinical evidence that doxorubicin combined with IL-1 may be beneficial in the clinical treatment of malignant melanoma and possibly other types of solid tumors. C1 NCI,DIV CANC BIOL DIAG & CTR,PATHOL LAB,BETHESDA,MD 20892. RP MIMNAUGH, EG (reprint author), NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892, USA. NR 46 TC 8 Z9 8 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0965-0407 J9 ONCOL RES JI Oncol. Res. PY 1992 VL 4 IS 10 BP 401 EP 412 PG 12 WC Oncology SC Oncology GA KR573 UT WOS:A1992KR57300002 PM 1292755 ER PT B AU DICHIRO, G AF DICHIRO, G BE Zappoli, F Martelli, A TI FORM AND FUNCTION IN THE NEURORADIOLOGICAL IMAGE SO OTTORINO ROSSI AWARD CONFERENCE: CONGRESS ON NEURORADIOLOGY IN PAVIA LA English DT Proceedings Paper CT Congress on Neuroradiology in Pavia CY JUN 15-16, 1992 CL PAVIA, ITALY C1 NIH,NEURORADIOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EDIZIONI CENTAURO PI UDINE PA VIA COSATTINI, 32, 33100 UDINE, ITALY BN 88-85980-09-0 PY 1992 BP 7 EP 22 PG 16 WC Clinical Neurology; Neurosciences; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BZ87Q UT WOS:A1992BZ87Q00001 ER PT B AU INSEL, TR SHAPIRO, LE AF INSEL, TR SHAPIRO, LE BE PEDERSEN, CA CALDWELL, JD JIRIKOWSKI, GF INSEL, TR TI OXYTOCIN RECEPTORS AND MATERNAL-BEHAVIOR SO OXYTOCIN IN MATERNAL, SEXUAL, AND SOCIAL BEHAVIORS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Proceedings Paper CT CONF ON OXYTOCIN IN MATERNAL, SEXUAL, AND SOCIAL BEHAVIORS CY MAY 22, 1991 CL ARLINGTON, VA SP NEW YORK ACAD SCI, NATL SCI FDN, BURROUGHS WELLCOME, R W JOHNSON PHARM RES INST RP INSEL, TR (reprint author), NIMH,CLIN SCI LAB,POB 289,POOLESVILLE,MD 20837, USA. NR 0 TC 41 Z9 41 U1 0 U2 6 PU NEW YORK ACAD SCIENCES PI NEW YORK PA NEW YORK BN 0-89766-699-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1992 VL 652 BP 122 EP 141 DI 10.1111/j.1749-6632.1992.tb34350.x PG 20 WC Behavioral Sciences; Physiology SC Behavioral Sciences; Physiology GA BW42X UT WOS:A1992BW42X00010 PM 1320825 ER PT B AU WITT, DM INSEL, TR AF WITT, DM INSEL, TR BE PEDERSEN, CA CALDWELL, JD JIRIKOWSKI, GF INSEL, TR TI CENTRAL OXYTOCIN ANTAGONISM DECREASES FEMALE REPRODUCTIVE-BEHAVIOR SO OXYTOCIN IN MATERNAL, SEXUAL, AND SOCIAL BEHAVIORS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Proceedings Paper CT CONF ON OXYTOCIN IN MATERNAL, SEXUAL, AND SOCIAL BEHAVIORS CY MAY 22, 1991 CL ARLINGTON, VA SP NEW YORK ACAD SCI, NATL SCI FDN, BURROUGHS WELLCOME, R W JOHNSON PHARM RES INST RP WITT, DM (reprint author), NIMH,CLIN SCI LAB,POOLESVILLE,MD 20837, USA. NR 0 TC 11 Z9 11 U1 1 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA NEW YORK BN 0-89766-699-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1992 VL 652 BP 445 EP 447 DI 10.1111/j.1749-6632.1992.tb34379.x PG 3 WC Behavioral Sciences; Physiology SC Behavioral Sciences; Physiology GA BW42X UT WOS:A1992BW42X00039 PM 1320836 ER PT B AU SHAPIRO, LE INSEL, TR AF SHAPIRO, LE INSEL, TR BE PEDERSEN, CA CALDWELL, JD JIRIKOWSKI, GF INSEL, TR TI OXYTOCIN RECEPTOR DISTRIBUTION REFLECTS SOCIAL-ORGANIZATION IN MONOGAMOUS AND POLYGAMOUS VOLES SO OXYTOCIN IN MATERNAL, SEXUAL, AND SOCIAL BEHAVIORS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Proceedings Paper CT CONF ON OXYTOCIN IN MATERNAL, SEXUAL, AND SOCIAL BEHAVIORS CY MAY 22, 1991 CL ARLINGTON, VA SP NEW YORK ACAD SCI, NATL SCI FDN, BURROUGHS WELLCOME, R W JOHNSON PHARM RES INST RP SHAPIRO, LE (reprint author), NIMH,CLIN SCI LAB,POOLESVILLE,MD 20837, USA. NR 0 TC 13 Z9 13 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA NEW YORK BN 0-89766-699-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1992 VL 652 BP 448 EP 451 DI 10.1111/j.1749-6632.1992.tb34380.x PG 4 WC Behavioral Sciences; Physiology SC Behavioral Sciences; Physiology GA BW42X UT WOS:A1992BW42X00040 PM 1320837 ER PT B AU WINSLOW, JT INSEL, TR AF WINSLOW, JT INSEL, TR BE PEDERSEN, CA CALDWELL, JD JIRIKOWSKI, GF INSEL, TR TI SOCIAL AND ENVIRONMENTAL DETERMINANTS OF CENTRALLY ADMINISTERED OXYTOCIN EFFECTS ON MALE SQUIRREL-MONKEY BEHAVIOR SO OXYTOCIN IN MATERNAL, SEXUAL, AND SOCIAL BEHAVIORS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Proceedings Paper CT CONF ON OXYTOCIN IN MATERNAL, SEXUAL, AND SOCIAL BEHAVIORS CY MAY 22, 1991 CL ARLINGTON, VA SP NEW YORK ACAD SCI, NATL SCI FDN, BURROUGHS WELLCOME, R W JOHNSON PHARM RES INST RP WINSLOW, JT (reprint author), NIMH,HIHAC,CLIN SCI LAB,POOLESVILLE,MD 20837, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA NEW YORK BN 0-89766-699-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1992 VL 652 BP 452 EP 455 DI 10.1111/j.1749-6632.1992.tb34381.x PG 4 WC Behavioral Sciences; Physiology SC Behavioral Sciences; Physiology GA BW42X UT WOS:A1992BW42X00041 PM 1626846 ER PT J AU DUBNER, R AF DUBNER, R TI HYPERALGESIA AND EXPANDED RECEPTIVE-FIELDS SO PAIN LA English DT Editorial Material ID DORSAL HORN NEURONS; RAT SPINAL-CORD; MECHANISMS; CELLS; PAIN; INFLAMMATION; STIMULATION; INJURY RP DUBNER, R (reprint author), NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892, USA. NR 16 TC 53 Z9 53 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JAN PY 1992 VL 48 IS 1 BP 3 EP 4 DI 10.1016/0304-3959(92)90124-T PG 2 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA GX020 UT WOS:A1992GX02000001 PM 1738572 ER PT J AU OTTESEN, EA AF OTTESEN, EA TI INFECTION AND DISEASE IN LYMPHATIC FILARIASIS - AN IMMUNOLOGICAL PERSPECTIVE SO PARASITOLOGY LA English DT Article DE LYMPHATIC; FILARIASIS; IMMUNOLOGICAL PERSPECTIVE; DISEASE; INFECTION ID CLINICAL MANIFESTATIONS; BRUGIA-PAHANGI; ANTIGENS; MALAYI; IGG; UNRESPONSIVENESS; RECOGNITION; MICE AB The basic tenet of the immunological perspective of filarial disease is that differential immune responsiveness among individuals exposed to infection results in the different clinical manifestations that develop. The mechanisms involved in this differential responsiveness appear to reflect different T-cell cytokine response patterns. Asymptomatic patients with the clinically silent presentation of 'asymptomatic microfilaraemia', who have been previously described as being 'immunosuppressed' with respect to their generating pro-inflammatory (Th1-type) immune responses to parasite antigen, are now recognized to be fully responsive to parasite antigen but to produce cytokines and mediators that have primarily anti-inflammatory (Th2-like) effects. Studies with immunodeficient mice have indicated the existence of two alternative pathways to the development of lymphatic pathology: one dependent on the induction of inflammatory reactions by the host immune response, the other entirely independent of the immune system and reflecting the direct actions of the parasite or its products on the lymphatics. As histopathology of affected human lymphatics is consistent with this hypothesis, it may be that the lymphatic pathology seen normally in the amicrofilaraemic, highly immunoresponsive infected patients derives from inflammation induced by immune responses to parasite antigen, whereas the lymphatic pathology sometimes seen coexisting with the 'immunosuppressed' state of asymptomatic microfilaraemia actually reflects lymphatic damage that is not immunologically mediated. Though little information exists about the 'natural history' of lymphatic filariasis, there is no evidence for an inevitable progression from one clinical form to another. Instead, there appears to be a definite plasticity in the response that depends on prior (? pre-natal) and current exposure to the parasite as well as on the immunomodulatory effects it induces. This plasticity does not appear to be complete, however, as there is no evidence that a chronically infected host who has developed strong pro-inflammatory immune responses can subsequently become sufficiently 'down-regulated' to support an asymptomatic microfilaraemia type of infection. Another possible constraint to the plasticity of the clinical and immunological responses may be the genetic determination of certain unusual syndromes, such as tropical pulmonary eosinophilia or TPE, though this hypothesis remains to be proven. RP OTTESEN, EA (reprint author), NIH,PARASIT DIS LAB,BETHESDA,MD 20892, USA. NR 36 TC 137 Z9 141 U1 1 U2 8 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0031-1820 J9 PARASITOLOGY JI Parasitology PY 1992 VL 104 SU S BP S71 EP S79 PG 9 WC Parasitology SC Parasitology GA HN834 UT WOS:A1992HN83400007 PM 1589302 ER PT J AU CARTER, CA VOLLMER, G KAUFMAN, DG AF CARTER, CA VOLLMER, G KAUFMAN, DG TI EFFECTS OF THE SV40 LARGE T-ANTIGEN AND EJ RAS ONCOGENE ON FIBRONECTIN LOCALIZATION IN HUMAN ENDOMETRIAL CELLS AS VIEWED BY CONFOCAL LASER SCANNING MICROSCOPY SO PATHOBIOLOGY LA English DT Article DE FIBRONECTIN; CONFOCAL MICROSCOPY; ENDOMETRIAL STROMAL CELLS; HUMAN; SV40 LARGE T-ANTIGEN; EJ RAS ONCOGENE ID CULTURED-CELLS; TRANSFORMATION; RECEPTOR; SURFACE; TUMORIGENICITY; IDENTIFICATION; EXPRESSION; INVITRO; CANCER; RNA AB We utilized confocal laser scanning microscopy to examine the localization of fibronectin deposition in cultures of human endometrial stromal cells. We found that fibronectin in normal human endometrial stromal cell cultures was both intracellular, occurring in rough endoplasmic reticulum and in perinuclear regions, and extracellular, occurring diffusely over the entire cell surface. Endometrial stromal cells were transfected with a plasmid containing an origin-defective Simian Virus 40 (SV40) which codes for a temperature-sensitive large T antigen. When these cells were placed under temperature-restrictive conditions for large T-antigen function, they exhibited staining patterns similar to normal endometrial cells. Fibronectin deposition in cultures of partially or fully transformed endometrial cells was not intracellular as in normal cells, but was localized primarily between cells. Cells expressing the SV40 large T antigen deposited fibronectin mainly in parallel clumps between cells. Cells expressing both the SV40 large T antigen and the EJ ras oncogene, at high cell density, displayed networks of fibronectin arranged in matrix-like patterns between cells. The malignant cell line examined, sarcoma cells, also exhibited fibronectin networks between cells. Cell density affected fibronectin deposition in endometrial stromal cells expressing the EJ ras oncogene. At low density, cells expressing the SV40 large T antigen and the EJ ras oncogene displayed diffuse fibronectin patterns and, at high density, these cells formed colonies with networks of fibronectin between cells. C1 MED UNIV LUBECK,INST BIOCHEM ENDOKRINOL,LUBECK,GERMANY. UNIV N CAROLINA,COMPREHENS CANC RES CTR,DEPT PATHOL & LINEBERGER,CHAPEL HILL,NC 27514. RP CARTER, CA (reprint author), NIEHS,EXPTL CARCINOGENESIS & MUTAGENESIS BRANCH,POB 12233,RES TRIANGLE PK,NC 27709, USA. FU NCI NIH HHS [CA31733]; NIEHS NIH HHS [ES07017] NR 31 TC 4 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-2008 J9 PATHOBIOLOGY JI Pathobiology PD JAN-FEB PY 1992 VL 60 IS 1 BP 33 EP 41 DI 10.1159/000163694 PG 9 WC Cell Biology; Pathology SC Cell Biology; Pathology GA HB319 UT WOS:A1992HB31900006 PM 1543549 ER PT J AU GERSTEN, DM HEARING, VJ AF GERSTEN, DM HEARING, VJ TI ANTIGENS OF MURINE MELANOMA AND THEIR CROSS-SPECIES REACTIVITY SO PATHOBIOLOGY LA English DT Article DE MELANOMA; ANTIGENS; MURINE ID SYNGENEIC MONOCLONAL-ANTIBODIES; CELL-SURFACE GLYCOPROTEIN; HUMAN-MALIGNANT-MELANOMA; BEARING B-16 MELANOMA; TUMOR REJECTION; AUTOLOGOUS ANTIBODY; METASTATIC ACTIVITY; IMMUNE-RESPONSE; MOUSE MELANOMA; EXPRESSION AB Many investigators have taken a two-stage approach to the study of tumor antigens. The first is the evaluation of antigens produced by animal tumors and the second is the determination of the extent to which animal antigens have relevant human homologs. Accordingly, we discuss the known protein antigens of murine melanoma with emphasis on those expressed by more than one species. These include six mouse-specific and five cross-species antigens, and 1 human antigen transfected into mouse cells. Of the five cross-species antigens, B700 and HMW have been demonstrated in four different species, making them candidate 'pan-melanoma' antigens. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. RP GERSTEN, DM (reprint author), GEORGETOWN UNIV,MED CTR,DEPT PATHOL,3900 RESERVOIR RD NW,WASHINGTON,DC 20007, USA. NR 81 TC 7 Z9 7 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-2008 J9 PATHOBIOLOGY JI Pathobiology PD JAN-FEB PY 1992 VL 60 IS 1 BP 49 EP 56 DI 10.1159/000163697 PG 8 WC Cell Biology; Pathology SC Cell Biology; Pathology GA HB319 UT WOS:A1992HB31900009 PM 1543551 ER PT J AU YANOVSKI, JA NELSON, LM WILLIS, ED CUTLER, GB AF YANOVSKI, JA NELSON, LM WILLIS, ED CUTLER, GB TI REPEATED, CHILDHOOD VAGINAL BLEEDING IS NOT ALWAYS PRECOCIOUS PUBERTY SO PEDIATRICS LA English DT Note ID VULVOVAGINITIS; VAGINITIS; CHILDREN; GIRLS C1 CHILDRENS HOSP,PHILADELPHIA,PA 19104. RP YANOVSKI, JA (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,9000 ROCKVILLE PIKE,BLDG 10,RM 10N262,BETHESDA,MD 20892, USA. NR 13 TC 1 Z9 2 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 JAN PY 1992 VL 89 IS 1 BP 149 EP 151 PG 3 WC Pediatrics SC Pediatrics GA GY514 UT WOS:A1992GY51400031 PM 1728002 ER PT B AU POLLARD, HB ROJAS, E BURNS, AL AF POLLARD, HB ROJAS, E BURNS, AL BE JOOSE, J BUIJS, RM TILDERS, FJH TI SYNEXIN (ANNEXIN-VII) AND MEMBRANE-FUSION DURING THE PROCESS OF EXOCYTOTIC SECRETION SO PEPTIDERGIC NEURON SE PROGRESS IN BRAIN RESEARCH LA English DT Proceedings Paper CT 11TH INTERNATIONAL SYMP ON NEUROSECRETION : PEPTIDERGIC NEURON CY JUN 10-14, 1991 CL VRIJE UNIV AMSTERDAM, AMSTERDAM, NETHERLANDS SP ROYAL NETHERLAND ACAD ARTS & SCI, SAAL VAN ZWANENBERGSTICHTING, DUPHAR, ORGANON INT, VRIJE UNIV AMSTERDAM, FAC BIOL HO VRIJE UNIV AMSTERDAM RP POLLARD, HB (reprint author), NIDDKD,CELL BIOL & GENET LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL B V PI AMSTERDAM PA AMSTERDAM BN 0-444-81457-4 J9 PROG BRAIN RES PY 1992 VL 92 BP 247 EP 255 DI 10.1016/S0079-6123(08)61180-2 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA BW67V UT WOS:A1992BW67V00021 PM 1284613 ER PT J AU PICKWORTH, WB KLEIN, SA GEORGE, FR HENNINGFIELD, JE AF PICKWORTH, WB KLEIN, SA GEORGE, FR HENNINGFIELD, JE TI ACETAMINOPHEN FAILS TO INHIBIT ETHANOL-INDUCED SUBJECTIVE EFFECTS IN HUMAN VOLUNTEERS SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE ACETAMINOPHEN; ETHANOL; PROSTAGLANDIN INHIBITORS; PARACETAMOL ID EXPLAINS ANTIPYRETIC ACTIVITY; PROSTAGLANDIN SYNTHETASE; PARACETAMOL 4-ACETAMIDOPHENOL; CYCLOOXYGENASE INHIBITORS; MOTOR IMPAIRMENT; TIME COURSE; ALCOHOL; BRAIN; PERFORMANCE; ACID AB In animals, ethanol causes some of its CNS effects by releasing prostaglandins (PG); this is demonstrated by reports that prostaglandin synthetase inhibitors (PGSIs) diminish ethanol-induced effects. However, use of animals in these studies has precluded testing for subjective effects. We studied the interaction of ethanol and acetaminophen, a PGSI, in a double-blind crossover experiment. Six adult males were given no drug or acetaminophen (0, 325, 650, 1300 or 1950 mg) 75 min before ethanol (total dose = 0.625 g/kg; five divided doses). Physiologic, subjective and performance measures were collected. Compared to the no drug condition, ethanol significantly increased ratings of drug "liking," "drunk," "sluggish" and "drug strength" and decreased ratings of "sober." Ethanol increased heart rate and acetaminophen did not diminish or enhance this effect. The failure to antagonize ethanol-induced subjective and physiologic effects by acetaminophen in humans may be due to species differences or inadequate dosage of the PGSI. It is also possible that subjective and certain physiologic effects of ethanol in humans are not mediated by prostaglandin-dependent neural processes. Nevertheless, the finding that at greater than typical analgesic doses, acetaminophen failed to prevent subjective effects of ethanol is of clinical significance. RP NIDA, ADDICT RES CTR, POB 5180, BALTIMORE, MD 21224 USA. NR 41 TC 1 Z9 2 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JAN PY 1992 VL 41 IS 1 BP 189 EP 194 DI 10.1016/0091-3057(92)90081-P PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA GW866 UT WOS:A1992GW86600032 PM 1539069 ER PT J AU HAMEL, E AF HAMEL, E TI NATURAL-PRODUCTS WHICH INTERACT WITH TUBULIN IN THE VINCA DOMAIN - MAYTANSINE, RHIZOXIN, PHOMOPSIN-A, DOLASTATIN-10 AND DOLASTATIN-15 AND HALICHONDRIN-B SO PHARMACOLOGY & THERAPEUTICS LA English DT Review ID MACROCYCLIC LACTONE ANTIBIOTICS; BOVINE BRAIN TUBULIN; AMINO-ACID-SEQUENCE; HAMSTER OVARY CELLS; ANTINEOPLASTIC AGENTS; ALPHA-TUBULIN; RHIZOPUS-CHINENSIS; MARINE SPONGE; BETA-TUBULIN; MICROTUBULE PROTEIN AB This paper summarizes published data on the interactions of tubulin with antimitotic compounds that inhibit the binding of vinca alkaloids to the protein. These are all relatively complex natural products isolated from higher plants, fungi and marine invertebrate animals. These agents are maytansine, rhizoxin, phomopsin A, dolastatins 10 and 15 and halichondrin B and their congeners. Effects on tubulin polymerization, ligand binding interactions and structure-activity relationships are emphasized. RP HAMEL, E (reprint author), NCI,DIV CANC TREATMENT,MOLEC PHARMACOL DEV THERAPEUT PROGRAM LAB,BETHESDA,MD 20892, USA. NR 102 TC 146 Z9 148 U1 0 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PY 1992 VL 55 IS 1 BP 31 EP 51 DI 10.1016/0163-7258(92)90028-X PG 21 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KG720 UT WOS:A1992KG72000002 PM 1287674 ER PT J AU THEODORE, WH AF THEODORE, WH TI RATIONAL USE OF ANTIEPILEPTIC DRUG LEVELS SO PHARMACOLOGY & THERAPEUTICS LA English DT Review ID FLUORESCENCE POLARIZATION IMMUNOASSAY; TONIC-CLONIC SEIZURES; VALPROIC ACID; EPILEPTIC PATIENTS; PLASMA-CONCENTRATIONS; INTRACTABLE EPILEPSY; SODIUM VALPROATE; ABSENCE SEIZURES; CARBAMAZEPINE; PHENYTOIN AB Antiepileptic drug (AED) levels are obtained frequently in clinical practice, but their complex relation to seizures or drug toxicity often makes interpretation of the results difficult. Research studies have not always taken into account clinical, as well as pharmacokinetic and pharmacodynamic, factors which may influence the drug level effect relationship. AED levels should be drawn at an appropriate time in relation to drug ingestion and clinical symptoms. Systematic investigations in selected patients, during which several levels are obtained, may be more rewarding than routine measurements in a large clinic population. RP THEODORE, WH (reprint author), NIH,CLIN EPILEPSY SECT,BETHESDA,MD 20892, USA. NR 70 TC 20 Z9 20 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PY 1992 VL 54 IS 3 BP 297 EP 305 DI 10.1016/0163-7258(92)90004-J PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KB012 UT WOS:A1992KB01200004 PM 1465479 ER PT J AU MARLEY, RJ ELMER, GI GOLDBERG, SR AF MARLEY, RJ ELMER, GI GOLDBERG, SR TI THE USE OF PHARMACOGENETIC TECHNIQUES IN DRUG-ABUSE RESEARCH SO PHARMACOLOGY & THERAPEUTICS LA English DT Review ID INBRED MOUSE STRAINS; LEVORPHANOL-INDUCED ANTINOCICEPTION; OPIATE RECEPTOR CONCENTRATION; MORPHINE-INDUCED ANALGESIA; OPEN-FIELD ACTIVITY; HOT-PLATE ASSAY; GENETIC-DIFFERENCES; SEIZURE SUSCEPTIBILITY; REGRESSION RESIDUALS; NICOTINIC RECEPTORS AB Pharmacogenetics, the study of genetic factors underlying individual differences in response to drugs, has proven useful for demonstrating that there are large genetic differences in response to a number of abused drugs. Pharmacogenetics also provides a number of useful tools for studying mechanisms underlying the effects of drugs. This review discusses pharmacogenetic techniques with potential utility for drug abuse research and provides examples of their use in studies of the effects of acute and chronic nicotine, cocaine and opiate administration. The importance of using genetically standardized animal models in behavioral and pharmacological research is also discussed. RP MARLEY, RJ (reprint author), NIDA,ADDICT RES CTR,BOX 5180,BALTIMORE,MD 21224, USA. NR 110 TC 13 Z9 13 U1 3 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PY 1992 VL 53 IS 2 BP 217 EP 237 DI 10.1016/0163-7258(92)90010-W PG 21 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JC918 UT WOS:A1992JC91800004 PM 1641407 ER PT J AU ELING, TE CURTIS, JF AF ELING, TE CURTIS, JF TI XENOBIOTIC METABOLISM BY PROSTAGLANDIN-H SYNTHASE SO PHARMACOLOGY & THERAPEUTICS LA English DT Review ID DEPENDENT MUTAGENIC ACTIVATION; VESICULAR GLAND MICROSOMES; FREE-RADICAL INTERMEDIATE; ENDOPEROXIDE SYNTHETASE; DNA ADDUCTS; HORSERADISH-PEROXIDASE; FORMING CYCLOOXYGENASE; COMPLEMENTARY-DNA; ARACHIDONIC-ACID; AROMATIC-AMINES AB During the metabolism of arachidonic acid by prostaglandin H synthase many chemicals including carcinogens are metabolized. These chemicals are metabolized by either the peroxidase activity of prostaglandin H synthase, the peroxyl radicals generated during arachidonic acid oxygenation, or a combination of these two mechanisms. In many cases, the chemical metabolism results in the formation of reactive metabolites that have mutagenic activity and potential carcinogenic activity. In other cases, the chemicals are detoxified. Chemical metabolism that occurs during arachidonic acid oxygenation may be an important determinate of chemical toxicity in extra-hepatic tissues. RP ELING, TE (reprint author), NIEHS,MOLEC BIOPHYS LAB,EICOSANOID BIOCHEM SECT,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 63 TC 63 Z9 65 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PY 1992 VL 53 IS 2 BP 261 EP 273 DI 10.1016/0163-7258(92)90012-O PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JC918 UT WOS:A1992JC91800006 PM 1641409 ER PT J AU LESCH, KP AULAKH, CS WOLOZIN, BL MURPHY, DL AF LESCH, KP AULAKH, CS WOLOZIN, BL MURPHY, DL TI SEROTONIN (5-HT) RECEPTOR, 5-HT TRANSPORTER AND G-PROTEIN-EFFECTOR EXPRESSION - IMPLICATIONS FOR DEPRESSION SO PHARMACOLOGY & TOXICOLOGY LA English DT Article; Proceedings Paper CT SATELLITE SYMP ON THE BIOLOGY AND PHARMACOTHERAPY OF MANIC-DEPRESSIVE DISORDERS : FROM MOLECULAR THEORIES TO CLINICAL-PRACTICE, AT THE 18TH CINP CONGRESS CY JUN 24-26, 1992 CL UNIV COPENHAGEN, DEPT PHARMACOL, COPENHAGEN, DENMARK SP CINP, DANISH MED RES COUNCIL, JANSSENPHARMA, ELI LILLY DENMARK, AP MOLLERS FOND, NOVO NORDISK, ORGANON, ROCHE, SCHERING BERLIN, SYNTHELABO SCANDINAVIA HO UNIV COPENHAGEN, DEPT PHARMACOL ID ANTIDEPRESSANT TREATMENTS; PHOSPHOLIPASE-C; LOCUS-CERULEUS; MESSENGER-RNA; CLONING; BRAIN; DESIPRAMINE; DECREASES; BINDING; SYSTEM C1 UNIV WURZBURG,DEPT PSYCHIAT,W-8700 WURZBURG,GERMANY. RP LESCH, KP (reprint author), NIMH,CLIN SCI LAB,CLIN NEUROPHARMACOL SECT,BETHESDA,MD 20892, USA. RI Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X NR 30 TC 23 Z9 23 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0901-9928 J9 PHARMACOL TOXICOL JI Pharmacol. Toxicol. PY 1992 VL 71 SU 1 BP 49 EP 60 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA KA431 UT WOS:A1992KA43100007 PM 1480560 ER PT J AU POST, RM SUSAN, R WEISS, B AF POST, RM SUSAN, R WEISS, B TI SENSITIZATION, KINDLING, AND CARBAMAZEPINE - AN UPDATE ON THEIR IMPLICATIONS FOR THE COURSE OF AFFECTIVE-ILLNESS SO PHARMACOPSYCHIATRY LA English DT Article ID COCAINE; ANTICONVULSANT; PERSPECTIVES; SECRETION; MECHANISM; RAT RP POST, RM (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 22 TC 38 Z9 38 U1 0 U2 5 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0176-3679 J9 PHARMACOPSYCHIATRY JI Pharmacopsychiatry PD JAN PY 1992 VL 25 IS 1 BP 41 EP 43 DI 10.1055/s-2007-1014386 PG 3 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA HG522 UT WOS:A1992HG52200013 PM 1579606 ER PT J AU ROSENTHAL, NE WEHR, TA AF ROSENTHAL, NE WEHR, TA TI TOWARDS UNDERSTANDING THE MECHANISM OF ACTION OF LIGHT IN SEASONAL AFFECTIVE-DISORDER SO PHARMACOPSYCHIATRY LA English DT Article ID PLATELET H-3-IMIPRAMINE BINDING; MELATONIN SUPPRESSION; WINTER DEPRESSION; PHOTOTHERAPY; SEROTONIN; ANTIDEPRESSANT; UNIPOLAR; BIPOLAR; CYCLE RP ROSENTHAL, NE (reprint author), NIMH,ENVIRONM PSYCHIAT SECT,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 58 TC 50 Z9 50 U1 0 U2 2 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0176-3679 J9 PHARMACOPSYCHIATRY JI Pharmacopsychiatry PD JAN PY 1992 VL 25 IS 1 BP 56 EP 60 DI 10.1055/s-2007-1014389 PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA HG522 UT WOS:A1992HG52200016 PM 1579608 ER PT S AU LANE, MA INGRAM, DK CUTLER, RG KNAPKA, JJ BARNARD, DE ROTH, GS AF LANE, MA INGRAM, DK CUTLER, RG KNAPKA, JJ BARNARD, DE ROTH, GS BE Fabris, N Harman, D Knook, DL Steinhagenthiessen, E Zsnagy, I TI DIETARY RESTRICTION IN NONHUMAN-PRIMATES - PROGRESS REPORT ON THE NIA STUDY SO PHYSIOPATHOLOGICAL PROCESSES OF AGING: TOWARDS A MULTICAUSAL INTERPRETATION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Proceedings Paper CT 4TH INTERNATION CONGRESS ON PHYSIOPATHOLOGICAL PROCESSES OF AGING : TOWARDS A MULTICAUSAL INTERPRETATION CY JUN 26-29, 1991 CL ANCONA, ITALY SP INT ASSOC BIOMED GERONTOL RP LANE, MA (reprint author), NIA,FRANCIS SCOTT KEY MED CTR,GERONTOL RES CTR,NATHAN W SHOCK LABS,BALTIMORE,MD 21224, USA. NR 0 TC 55 Z9 56 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA NEW YORK SN 0077-8923 BN 0-89766-744-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1992 VL 673 BP 36 EP 45 DI 10.1111/j.1749-6632.1992.tb27434.x PG 10 WC Geriatrics & Gerontology; Pathology; Physiology SC Geriatrics & Gerontology; Pathology; Physiology GA BX33P UT WOS:A1992BX33P00006 PM 1485732 ER PT S AU XIAO, RP LAKATTA, EG AF XIAO, RP LAKATTA, EG BE Fabris, N Harman, D Knook, DL Steinhagenthiessen, E Zsnagy, I TI DETERIORATION OF BETA-ADRENERGIC MODULATION OF CARDIOVASCULAR FUNCTION WITH AGING SO PHYSIOPATHOLOGICAL PROCESSES OF AGING: TOWARDS A MULTICAUSAL INTERPRETATION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Proceedings Paper CT 4TH INTERNATION CONGRESS ON PHYSIOPATHOLOGICAL PROCESSES OF AGING : TOWARDS A MULTICAUSAL INTERPRETATION CY JUN 26-29, 1991 CL ANCONA, ITALY SP INT ASSOC BIOMED GERONTOL RP LAKATTA, EG (reprint author), NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224, USA. NR 0 TC 32 Z9 32 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA NEW YORK SN 0077-8923 BN 0-89766-744-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1992 VL 673 BP 293 EP 310 DI 10.1111/j.1749-6632.1992.tb27465.x PG 18 WC Geriatrics & Gerontology; Pathology; Physiology SC Geriatrics & Gerontology; Pathology; Physiology GA BX33P UT WOS:A1992BX33P00037 PM 1336647 ER PT J AU TSUKAMOTO, K JIMENEZ, M HEARING, VJ AF TSUKAMOTO, K JIMENEZ, M HEARING, VJ TI THE NATURE OF TYROSINASE ISOZYMES SO PIGMENT CELL RESEARCH LA English DT Article; Proceedings Paper CT 14TH INTERNATIONAL PIGMENT CELL CONF CY OCT 31-NOV 04, 1990 CL KOBE, JAPAN SP PAN AMERICAN SOC PIGMENT CELL RES, EUROPEAN SOC PIGMENT CELL RES, JAPANESE SOC PIGMENT CELL RES ID DOPACHROME CONVERSION FACTOR; MAMMALIAN TYROSINASE; MOUSE TYROSINASE; MELANOMA-CELLS; BROWN LOCUS; METAL-IONS; CDNA; PIGMENTATION; ALBINO; CLONE C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. UNIV MURCIA,FAC VET,UNIDA DOCENTE BIOL,MURCIA,SPAIN. RP TSUKAMOTO, K (reprint author), YAMANASHI MED COLL,DEPT DERMATOL,1110 SHIMOKATO,NAKAKOMA,YAMANASHI 40938,JAPAN. NR 29 TC 2 Z9 2 U1 1 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PY 1992 SU 2 BP 84 EP 89 PG 6 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA JD410 UT WOS:A1992JD41000014 ER PT J AU TSUKAMOTO, K UEDA, M HEARING, VJ AF TSUKAMOTO, K UEDA, M HEARING, VJ TI MELANOGENESIS IN MURINE MELANOCYTES IS SUPPRESSED BY INFECTION WITH THE V-RAS(HA) ONCOGENE SO PIGMENT CELL RESEARCH LA English DT Article; Proceedings Paper CT 14TH INTERNATIONAL PIGMENT CELL CONF CY OCT 31-NOV 04, 1990 CL KOBE, JAPAN SP PAN AMERICAN SOC PIGMENT CELL RES, EUROPEAN SOC PIGMENT CELL RES, JAPANESE SOC PIGMENT CELL RES ID MAMMALIAN TYROSINASE; GROWTH; RAS C1 YAMANASHI MED COLL,DEPT DERMATOL,NAKAKOMA,YAMANASHI 40938,JAPAN. NIH,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. KOBE UNIV,SCH MED,DEPT DERMATOL,CHUO KU,KOBE 650,JAPAN. RP TSUKAMOTO, K (reprint author), NIH,CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 8 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 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PY 1992 SU 2 BP 181 EP 184 PG 4 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA JD410 UT WOS:A1992JD41000028 ER PT J AU WILBUR, WJ AF WILBUR, WJ TI A RETRIEVAL-SYSTEM BASED ON AUTOMATIC RELEVANCE WEIGHTING OF SEARCH TERMS SO PROCEEDINGS OF THE ASIS ANNUAL MEETING LA English DT Article; Proceedings Paper CT 55TH ANNUAL MEETING OF THE AMERICAN SOC FOR INFORMATION SCIENCE CY OCT 26-29, 1992 CL PITTSBURGH, PA SP AMER SOC INFORMAT SCI ID DOCUMENT-RETRIEVAL AB We have developed a retrieval methodology based on relevance weighting of search terms with an automatic implementation. It is founded on the familiar Bayesian formulation of the probability of relevance as a function of term occurrence where the contribution from individual terms is assumed to be independent. However our formulation departs from the usual in that it is based on considering pairs of documents, and terms contribute to the score (log odds of relevance) in a symmetric manner. Terms which appear in both documents in a pair contribute positively to the score and terms that occur in only one document contribute negatively. This allows the length of a document to become a negative factor in the scoring much as it is in the cosine formula commonly used in vector retrieval. As a consequence each term has two weights associated with it, one positive which is its contribution when it occurs in both documents of a pair, and one negative which is its contribution when it occurs in only one document of a pair. A method is found to incorporate local term weights based on within document term frequencies, into this retrieval scheme. We term the result the relevance pairs(RP) model. We obtain the necessary statistics to estimate the weights in the model by substituting the set of all highly rated document pairs identified by a successful retrieval method for the set of all relevant pairs of documents. For the successful retrieval method we use the vector cosine (VC) model. In our test environment we find improved retrieval by the RP model when compared with the VC model. RP WILBUR, WJ (reprint author), NATL LIB MED,NCBI,BETHESDA,MD 20209, USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU INFORMATION TODAY INC PI MEDFORD PA 143 OLD MARLTON PIKE, MEDFORD, NJ 08055-8750 SN 0044-7870 J9 P ASIS ANNU MEET JI Proc. ASIS Annu. Meet. PY 1992 VL 29 BP 216 EP 220 PG 5 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA JV325 UT WOS:A1992JV32500030 ER PT J AU HUMPHREY, SM AF HUMPHREY, SM TI EXAMPLE-BASED TUTORIAL ON THE USE OF FRAMES IN KNOWLEDGE-BASED INFORMATION-RETRIEVAL SYSTEMS SO PROCEEDINGS OF THE ASIS ANNUAL MEETING LA English DT Meeting Abstract C1 NATL LIB MED,BETHESDA,MD 20209. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMATION TODAY INC PI MEDFORD PA 143 OLD MARLTON PIKE, MEDFORD, NJ 08055-8750 SN 0044-7870 J9 P ASIS ANNU MEET JI Proc. ASIS Annu. Meet. PY 1992 VL 29 BP 318 EP 318 PG 1 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA JV325 UT WOS:A1992JV32500082 ER PT J AU MULLEN, CA KILSTRUP, M BLAESE, RM AF MULLEN, CA KILSTRUP, M BLAESE, RM TI TRANSFER OF THE BACTERIAL GENE FOR CYTOSINE DEAMINASE TO MAMMALIAN-CELLS CONFERS LETHAL SENSITIVITY TO 5-FLUOROCYTOSINE - A NEGATIVE SELECTION SYSTEM SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE RETROVIRAL VECTOR; GENE THERAPY; SUICIDE VECTOR; 5-FLUOROURACIL ID RETROVIRAL VECTORS; RECOMBINATION; EXPRESSION; PURINE AB Expression of the bacterial gene for cytosine deaminase (CD; EC 3.5.4.1) in mammalian cells was evaluated as a negative selection system or suicide vector for potential use in gene transfer studies and therapies. Mammalian cells, unlike certain bacteria and fungi, do not contain the enzyme CD and do not ordinarily metabolize cytosine to uracil. Nor do they metabolize the innocuous compound 5-fluorocytosine to the highly toxic compound 5-fluorouracil. The Escherichia coli CD gene underwent PCR oligonucleotide-directed mutagenesis to enhance its expression in a eukaryotic system and it was then cloned into an expression vector, pLXSN, that also contains a neomycin-resistance gene. Murine fibroblast lines were transfected with the plasmid and subjected to brief selection in the neomycin analogue G418. Lysates from these cell populations exhibited significant CD activity detected by conversion of radiolabeled cytosine to uracil. In clonogenic assays transfected cells expressing CD were selectively killed by incubation in 5-fluorocytosine, whereas control cell lines were not. Dose-response studies evaluating [H-3]thymidine incorporation or cloning efficiency demonstrated profound inhibition at and above 65-mu-g of 5-fluorocytosine per ml. Mixed cellular assays showed that CD-positive cells could be eliminated without bystander killing of other cells. Retrovirus-mediated CD gene transfer into various tissues was also demonstrated. Thus CD, with its ability to produce the toxic antimetabolite 5-fluorouracil from 5-fluorocytosine, may be useful as a negative selection system for studies and treatments employing gene transfer techniques. C1 UNIV COPENHAGEN,INST BIOL CHEM B,DK-1307 COPENHAGEN K,DENMARK. RP MULLEN, CA (reprint author), NCI,METAB BRANCH,CELLULAR IMMUNOL SECT,BLDG 10,ROOM 6B05,BETHESDA,MD 20892, USA. NR 21 TC 445 Z9 461 U1 1 U2 8 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 1 PY 1992 VL 89 IS 1 BP 33 EP 37 DI 10.1073/pnas.89.1.33 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GY047 UT WOS:A1992GY04700008 PM 1729703 ER PT J AU BEGLEY, CG LIPKOWITZ, S GOBEL, V MAHON, KA BERTNESS, V GREEN, AR GOUGH, NM KIRSCH, IR AF BEGLEY, CG LIPKOWITZ, S GOBEL, V MAHON, KA BERTNESS, V GREEN, AR GOUGH, NM KIRSCH, IR TI MOLECULAR CHARACTERIZATION OF NSCL, A GENE ENCODING A HELIX LOOP HELIX PROTEIN EXPRESSED IN THE DEVELOPING NERVOUS-SYSTEM SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HEMATOPOIESIS; NEUROGENESIS; TRANSCRIPTION FACTOR; GENETIC LINKAGE ID T-CELL LEUKEMIA; DNA-BINDING; TAL-1 GENE; SCL GENE; TRANSLOCATION; MOTIF; SEQUENCES; COMPLEX; REGION; MYC AB We report here the molecular cloning and chromosomal localization of an additional member of the helix-loop-helix (HLH) family of transcription factors, NSCL. The NSCL gene was identified based on its hybridization to the previously described hemopoietic HLH gene, SCL. Murine NSCL cDNA clones were obtained from a day 11.5 mouse embryo cDNA library. The coding region is 399 base pairs and encodes a predicted protein of 14.8 kDa. The nucleotide sequence shows 71% identity and the amino acid sequence shows 61% identity to murine SCL in the HLH domain. The NSCL protein-coding region terminates six amino acids beyond the second amphipathic helix of the HLH domain. Expression of NSCL was detected in RNA from mouse embryos between 9.5 and 14.5 days postcoitus, with maximum levels of expression at 10.5-12 days. Examination of 12- and 13-day mouse embryos by in situ hybridization revealed expression of NSCL in the developing nervous system. The NSCL gene was mapped to murine chromosome 1. The very restricted pattern of NSCL expression suggests an important role for this HLH protein in neurological development. C1 ROYAL MELBOURNE HOSP,DEPT DIAGNOST HAEMATOL,PARKVILLE,VIC 3050,AUSTRALIA. NCI,NAVY MED ONCOL BRANCH,BALTIMORE,MD 21201. NCI,METAB BRANCH,BETHESDA,MD 20892. NICHHD,MAMMALIAN GENES & DEV LAB,BETHESDA,MD 20814. RP BEGLEY, CG (reprint author), ROYAL MELBOURNE HOSP,WALTER & ELIZA HALL INST MED RES,PARKVILLE,VIC 3050,AUSTRALIA. NR 26 TC 119 Z9 121 U1 0 U2 1 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 1 PY 1992 VL 89 IS 1 BP 38 EP 42 DI 10.1073/pnas.89.1.38 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GY047 UT WOS:A1992GY04700009 PM 1729708 ER PT J AU CARPENTIER, JL PACCAUD, JP GORDEN, P RUTTER, WJ ORCI, L AF CARPENTIER, JL PACCAUD, JP GORDEN, P RUTTER, WJ ORCI, L TI INSULIN-INDUCED SURFACE REDISTRIBUTION REGULATES INTERNALIZATION OF THE INSULIN-RECEPTOR AND REQUIRES ITS AUTOPHOSPHORYLATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PHOSPHORYLATION; ENDOCYTOSIS ID CULTURED HUMAN-LYMPHOCYTES; LOW-DENSITY-LIPOPROTEIN; KINASE-ACTIVITY; MEDIATED INTERNALIZATION; COATED PITS; ENDOCYTOSIS; FIBROBLASTS; BINDING; CELLS; PHOSPHORYLATION AB The role of insulin-induced receptor autophosphorylation in its internalization was analyzed by comparing I-125-labeled insulin (I-125-insulin) internalization in Chinese hamster ovary (CHO) cell lines transfected with normal (CHO.T) or mutated insulin receptors. In four cell lines with a defect of insulin-induced autophosphorylation, I-125-insulin internalization was impaired. By contrast, in CHO.T cells and in two other CHO cell lines with amino acid deletions or insertions that do not perturb autophosphorylation, I-125-insulin internalization was not affected. A morphological analysis showed that the inhibition is linked to the ligand-specific surface redistribution in which the insulin-receptor complexes leave microvilli and concentrate on nonvillous segments of the membrane where endocytosis occurs. C1 NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,HORMONE RES INST,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT BIOCHEM & BIOPHYS,SAN FRANCISCO,CA 94143. RP CARPENTIER, JL (reprint author), UNIV GENEVA,MED CTR,INST HISTOL & EMBRYOL,DEPT MORPHOL,CH-1211 GENEVA 4,SWITZERLAND. NR 28 TC 60 Z9 61 U1 0 U2 0 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 1 PY 1992 VL 89 IS 1 BP 162 EP 166 DI 10.1073/pnas.89.1.162 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GY047 UT WOS:A1992GY04700035 PM 1729685 ER PT J AU BUKH, J PURCELL, RH MILLER, RH AF BUKH, J PURCELL, RH MILLER, RH TI IMPORTANCE OF PRIMER SELECTION FOR THE DETECTION OF HEPATITIS-C VIRUS-RNA WITH THE POLYMERASE CHAIN-REACTION ASSAY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NON-A, NON-B HEPATITIS; 5' NONCODING SEQUENCE; GENETIC HETEROGENEITY ID NON-B-HEPATITIS; NON-A; GENOME; SEQUENCE; LIVER; DONOR; JAPAN; ACID; PCR; DNA AB We compared four primer sets from conserved regions of the hepatitis C virus (HCV) genome for their ability to detect HCV RNA in a "nested" cDNA polymerase chain reaction assay on sera from 114 anti-HCV antibody-positive individuals from around the world. The different primer sets had equivalent sensitivity, detecting < 1 chimpanzee ID50 (dose that infects 50%) when tested against reference strain H of HCV. We tested equal amounts of RNA extracted from the serum of each individual with the four primer sets. The set derived from two highly conserved domains within the 5' noncoding (NC) region of the HCV genome, which also share significant similarity with Pestivirus 5' NC sequences, was the most effective at detecting HCV RNA. All samples positive for HCV RNA with any other primer set were also positive with the primer set from the 5' NC region, and the latter was at least 3 times more likely to detect HCV infection than a primer set from within the nonstructural protein 3-like gene region (P < 0.001). We had no false positive results in > 500 negative controls interspersed among the test samples. The 5' NC region primer set detected HCV-specific RNA, verified by high-stringency Southern blot hybridization and DNA sequencing, in 100% of 15 acute and 33 chronic non-A, non-B hepatitis patients from the United States, Europe, and Asia, and 10 hepatocellular carcinoma patients from Africa and Asia that tested negative for the hepatitis B virus-encoded surface antigen. In conclusion, use of an appropriate primer set is crucial for detecting HCV RNA in the serum of infected individuals. C1 NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892. NR 46 TC 225 Z9 229 U1 1 U2 3 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 1 PY 1992 VL 89 IS 1 BP 187 EP 191 DI 10.1073/pnas.89.1.187 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GY047 UT WOS:A1992GY04700040 PM 1309604 ER PT J AU WADA, K YOKOTANI, N HUNTER, C DOI, K WENTHOLD, RJ SHIMASAKI, S AF WADA, K YOKOTANI, N HUNTER, C DOI, K WENTHOLD, RJ SHIMASAKI, S TI DIFFERENTIAL EXPRESSION OF 2 DISTINCT FORMS OF MESSENGER-RNA ENCODING MEMBERS OF A DIPEPTIDYL AMINOPEPTIDASE FAMILY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ENDOPEPTIDASE 24.11 ENKEPHALINASE; AMINO-ACID SEQUENCE; MEMBRANE GLYCOPROTEIN; MOLECULAR-CLONING; COMPLEMENTARY-DNA; PEPTIDASE-IV; HUMAN-BRAIN; RAT-BRAIN; PROTEIN; CDNA AB We have identified two cDNAs encoding dipeptidyl aminopeptidase-like proteins (DPPXs) in both bovine and rat brains that have different N-terminal cytoplasmic domains but share an identical transmembrane domain and a long C-terminal extracellular domain. In both species, one of the cDNAs encodes a protein (designated DPPX-S) of 803 amino acid residues with a short cytoplasmic domain of 32 amino acids, and the other cDNA encodes a protein (designated DPPX-L) with a longer cytoplasmic domain-the bovine cDNA encodes 92 amino acids and the rat cDNA encodes 88 amino acids. The membrane topology of DPPX-S and -L is similar to that of other transmembrane peptidases, and DPPXs share almost-equal-to 30% identity and 50% similarity with reported yeast and rat liver dipeptidyl aminopeptidase amino acid sequences, suggesting that DPPX is a member of the dipeptidyl aminopeptidase family. DPPX-S mRNA is expressed in brain and some peripheral tissues including kidney, ovary, and testis; in contrast, DPPX-L mRNA is expressed almost exclusively in brain. No transcripts for either form are found in heart, liver, or spleen. In situ hybridization studies show that the two transcripts have different distributions in the brain. DPPX-L mRNA is expressed in limited regions of brain with the highest level of expression in the medial habenula. More widespread expression is seen for DPPX-S mRNA. The differential distribution of mRNAs for the DPPX-S and -L suggests that these proteins are involved in the metabolism of certain localized peptides and that the cytoplasmic domain may play a key role in determining the physiological specificity of DPPX. C1 WHITTIER INST DIABET & ENDOCRINOL,DEPT MOLEC ENDOCRINOL,LA JOLLA,CA 92037. RP WADA, K (reprint author), NIDOCD,NEUROCHEM LAB,BLDG 36,ROOM 5D08,BETHESDA,MD 20892, USA. NR 45 TC 88 Z9 91 U1 0 U2 1 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 1 PY 1992 VL 89 IS 1 BP 197 EP 201 DI 10.1073/pnas.89.1.197 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GY047 UT WOS:A1992GY04700042 PM 1729689 ER PT J AU MAO, SY ALBER, G RIVERA, J KOCHAN, J METZGER, H AF MAO, SY ALBER, G RIVERA, J KOCHAN, J METZGER, H TI INTERACTION OF AGGREGATED NATIVE AND MUTANT IGE RECEPTORS WITH THE CELLULAR SKELETON SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BASOPHILIC LEUKEMIA-CELLS; RBL-2H3 MAST-CELLS; IMMUNOGLOBULIN-E; HIGH-AFFINITY; TRANSFECTED CELLS; MASTOCYTOMA-CELLS; HISTAMINE-RELEASE; MEMBRANE SKELETON; LATERAL MOTION; CROSS-LINKING AB When aggregated, cell surface proteins become resistant to solubilization by detergents, presumably because of aggregation-induced or -stabilized interactions between the membrane protein and the cytoskeleton or plasma membrane skeleton. We genetically engineered variants of the tetrameric high-affinity receptor for IgE (Fc-epsilon-RI) to identify a site on its alpha, beta, or gamma-chains that mediates such putative interactions. Using flow cytofluorometry, we studied rat basophilic leukemia cells, transiently transfected COS cells, and stably transfected P815 cells bearing wild-type and mutated receptors. We observed that (i) solubilization was markedly dependent on the degree of aggregation, the extent varying somewhat with the cell type and, particularly at lower levels of aggregation, with the time after addition of detergent; (ii) truncation of no single cytoplasmic domain of the alpha, beta, or gamma-chains ablated the insolubilization effect; and (iii) incomplete receptors were also efficiently insolubilized by aggregation. Thus receptors consisting only of alpha and gamma-chains, a "receptor" consisting of only the ectodomain of the alpha-chain attached to the plasma membrane by a glycosyl-phosphatidyl inositol anchor, and "receptors" consisting only of minimally modified gamma-chains were resistant to solubilization after aggregation. We conclude that no unique subunit or domain of Fc-epsilon-RI mediates the insolubilization phenomenon. Our results support a model in which the bridging of membrane proteins leads to their becoming nonspecifically enmeshed in a network of membrane skeletal proteins on either the outside and/or the inside of the membrane so that dissolution of the lipid bilayer becomes irrelevant. C1 HOFFMANN LA ROCHE INC,DEPT MOLEC GENET,NUTLEY,NJ 07110. RP MAO, SY (reprint author), NIAMSD,BETHESDA,MD 20892, USA. NR 34 TC 35 Z9 35 U1 0 U2 0 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 1 PY 1992 VL 89 IS 1 BP 222 EP 226 DI 10.1073/pnas.89.1.222 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GY047 UT WOS:A1992GY04700047 PM 1530886 ER PT J AU MIKI, T BOTTARO, DP FLEMING, TP SMITH, CL BURGESS, WH CHAN, AML AARONSON, SA AF MIKI, T BOTTARO, DP FLEMING, TP SMITH, CL BURGESS, WH CHAN, AML AARONSON, SA TI DETERMINATION OF LIGAND-BINDING SPECIFICITY BY ALTERNATIVE SPLICING - 2 DISTINCT GROWTH-FACTOR RECEPTORS ENCODED BY A SINGLE GENE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE FIBROBLAST GROWTH FACTOR FAMILY; KERATINOCYTE GROWTH FACTOR; EXPRESSION CLONING; TYROSINE KINASE; TISSUE-SPECIFIC EXPRESSION ID CDNA LIBRARIES; CLONING; PURIFICATION; EXPRESSION; FORMS; CELLS; FGF AB Expression cDNA cloning and structural analysis of the human keratinocyte growth factor receptor (KGFR) revealed identity with one of the fibroblast growth factor (FGF) receptors encoded by the bek gene (FGFR-2), except for a divergent stretch of 49 amino acids in their extracellular domains. Binding assays demonstrated that the KGFR was a high-affinity receptor for both KGF and acidic FGF, while FGFR-2 showed high affinity for basic and acidic FGF but no detectable binding by KGF. Genomic analysis of the bek gene revealed two alternative exons responsible for the region of divergence between the two receptors. The KGFR transcript was specific to epithelial cells, and it appeared to be differentially regulated with respect to the alternative FGFR-2 transcript. Thus, two growth factor receptors with different ligand-binding specificities and expression patterns are encoded by alternative transcripts of the same gene. C1 AMER RED CROSS,JEROME H HOLLAND LAB BIOMED SCI,MOLEC BIOL LAB,ROCKVILLE,MD 20855. RP MIKI, T (reprint author), NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892, USA. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 21 TC 678 Z9 684 U1 0 U2 5 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 1 PY 1992 VL 89 IS 1 BP 246 EP 250 DI 10.1073/pnas.89.1.246 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GY047 UT WOS:A1992GY04700052 PM 1309608 ER PT J AU BIGGER, CAH STJOHN, J YAGI, H JERINA, DM DIPPLE, A AF BIGGER, CAH STJOHN, J YAGI, H JERINA, DM DIPPLE, A TI MUTAGENIC SPECIFICITIES OF 4 STEREOISOMERIC BENZO[C]PHENANTHRENE DIHYDRODIOL EPOXIDES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SHUTTLE VECTOR; POLYCYCLIC AROMATIC HYDROCARBON; MUTAGENIC SPECIFICITY; ENANTIOMERS ID SHUTTLE-VECTOR; MAMMALIAN-CELLS; DNA; 3,4-DIOL-1,2-EPOXIDES; CARCINOGEN; BENZO(C)PHENANTHRENE; MUTATIONS; PLASMID; ADENINE; ADDUCTS AB The pS189 shuttle vector carrying a supF target gene was used to compare the mutagenic specificities of the four configurational isomers of benzo[c]phenanthrene 3,4-dihydrodiol 1,2-epoxide. One of these isomers is the most tumorigenic dihydrodiol epoxide tested to date and another is essentially inactive as a tumorigen. Overall mutagenicities were not correlated with tumorigenicities, but each configurational isomer induced a unique spectrum of mutational hot spots in the supF target gene, which monitors primarily point mutations. It is suggested that the demonstrated isomer-specific selectivity for mutation targets within the supF gene may be indicative of a similar selectivity for one gene versus another and that such selectivity may be one determinant of relative tumorigenicity. C1 NCI,FREDERICK CANC RES & DEV CTR,BASIC RES PROGRAM,ADV BIOSCI LABS,FREDERICK,MD 21701. NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. FU NCI NIH HHS [N01-CO-74101] NR 28 TC 57 Z9 57 U1 0 U2 0 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 1 PY 1992 VL 89 IS 1 BP 368 EP 372 DI 10.1073/pnas.89.1.368 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GY047 UT WOS:A1992GY04700077 PM 1729707 ER PT J AU MILLER, A LIDER, O ROBERTS, AB SPORN, MB WEINER, HL AF MILLER, A LIDER, O ROBERTS, AB SPORN, MB WEINER, HL TI SUPPRESSOR T-CELLS GENERATED BY ORAL TOLERIZATION TO MYELIN BASIC-PROTEIN SUPPRESS BOTH INVITRO AND INVIVO IMMUNE-RESPONSES BY THE RELEASE OF TRANSFORMING GROWTH-FACTOR-BETA AFTER ANTIGEN-SPECIFIC TRIGGERING SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TOLERANCE; SUPPRESSOR T-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; NECROSIS FACTOR-ALPHA; LYMPHOCYTES-T; INHIBITION; TOLERANCE; EXPRESSION; FACTOR-BETA-1; TGF-BETA-1; MECHANISM; TISSUE AB Oral administration of myelin basic protein (MBP) is an effective way of suppressing experimental autoimmune encephalomyelitis (EAE). We have previously shown that such suppression is mediated by CD8+ T cells, which adoptively transfer protection and suppress immune responses in vitro. In the present study we have found that modulator cells from animals orally tolerized to MBP produce a suppressor factor upon stimulation with MBP in vitro that is specifically inhibited by anti-transforming growth factor-beta (TGF-beta) neutralizing antibodies. No effect was observed with antibodies to gamma-interferon, tumor necrosis factor-alpha/beta, or indomethacin. In addition, the active form of the type 1 isoform of TGF-beta-1 (TGF-beta-1) can be directly demonstrated in the supernatants of cells from animals orally tolerized to MBP or ovalbumin after antigen stimulation in vitro. Antiserum specific for TGF-beta-1 administered in vivo abrogated the protective effect of oral tolerization to MBP in EAE. Furthermore, injection of anti-TGF-beta-1 serum to nontolerized EAE animals resulted in an increase in severity and duration of disease. These results suggest that immunomodulation of EAE induced by oral tolerization to MBP and natural recovery mechanisms use a common immunoregulatory pathway that is dependent on TGF-beta-1. Implications of such an association are of therapeutic relevance to human autoimmune diseases and may help to explain one of the mechanisms involved in the mediation of active suppression by T cells. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. RP MILLER, A (reprint author), BRIGHAM & WOMENS HOSP,DEPT MED,DIV NEUROL,CTR NEUROL DIS,BOSTON,MA 02115, USA. FU FIC NIH HHS [1F05TW04418, 1CP]; PHS HHS [N529352] NR 51 TC 746 Z9 758 U1 0 U2 1 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 1 PY 1992 VL 89 IS 1 BP 421 EP 425 DI 10.1073/pnas.89.1.421 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GY047 UT WOS:A1992GY04700088 PM 1370356 ER PT J AU SWIETER, M MERGENHAGEN, SE SIRAGANIAN, RP AF SWIETER, M MERGENHAGEN, SE SIRAGANIAN, RP TI MICROENVIRONMENTAL FACTORS THAT INFLUENCE MAST-CELL PHENOTYPE AND FUNCTION SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Review ID CONNECTIVE-TISSUE-TYPE; GROWTH-ENHANCING ACTIVITY; C-KIT RECEPTOR; BONE-MARROW TRANSPLANTATION; TYROSINE KINASE RECEPTOR; STIMULATORY FACTOR-I; W-MUTANT MICE; T-CELL; W/WV MICE; PROTO-ONCOGENE RP SWIETER, M (reprint author), NIDR,IMMUNOL LAB,BLDG 10,RM 1A28,BETHESDA,MD 20892, USA. NR 123 TC 23 Z9 23 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD JAN PY 1992 VL 199 IS 1 BP 22 EP 33 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA GW106 UT WOS:A1992GW10600003 PM 1728034 ER PT J AU SOKOLOFF, L AF SOKOLOFF, L TI THE BRAIN AS A CHEMICAL MACHINE SO PROGRESS IN BRAIN RESEARCH LA English DT Review ID CEREBRAL GLUCOSE-UTILIZATION; CENTRAL NERVOUS-SYSTEM; FUNCTIONAL-ACTIVITY; ENERGY-METABOLISM; ELECTRICAL-STIMULATION; RAT; LOCALIZATION; GANGLION RP SOKOLOFF, L (reprint author), NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892, USA. RI Sykova, Eva/H-2659-2014 NR 28 TC 58 Z9 58 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 J9 PROG BRAIN RES JI Prog. Brain Res. PY 1992 VL 94 BP 19 EP 33 PG 15 WC Neurosciences SC Neurosciences & Neurology GA KG215 UT WOS:A1992KG21500002 PM 1337612 ER PT J AU POLLARD, HB ROJAS, E BURNS, AL AF POLLARD, HB ROJAS, E BURNS, AL TI SYNEXIN (ANNEXIN-VII) AND MEMBRANE-FUSION DURING THE PROCESS OF EXOCYTOTIC SECRETION SO PROGRESS IN BRAIN RESEARCH LA English DT Review ID FORMS CALCIUM CHANNELS; BILAYER-MEMBRANES; PROTEIN; CHAIN; AGGREGATION; SIMULATION; CALPACTIN; DYNAMICS; VESICLES; MODEL RP POLLARD, HB (reprint author), NIDDKD,CELL BIOL & GENET LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 26 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 J9 PROG BRAIN RES JI Prog. Brain Res. PY 1992 VL 92 BP 247 EP 255 DI 10.1016/S0079-6123(08)61180-2 PG 9 WC Neurosciences SC Neurosciences & Neurology GA JU103 UT WOS:A1992JU10300021 PM 1284613 ER PT J AU FREED, MA AF FREED, MA TI GABAERGIC CIRCUITS IN THE MAMMALIAN RETINA SO PROGRESS IN BRAIN RESEARCH LA English DT Review ID GAMMA-AMINOBUTYRIC-ACID; GABA-LIKE IMMUNOREACTIVITY; CHOLINERGIC AMACRINE CELLS; INNER PLEXIFORM LAYER; INDOLEAMINE-ACCUMULATING NEURONS; MACAQUE MONKEY RETINA; DECARBOXYLASE-LIKE IMMUNOREACTIVITIES; ELECTRON MICROSCOPICAL OBSERVATIONS; ROD BIPOLAR CELLS; CAT RETINA RP FREED, MA (reprint author), NIH,BLDG 36,ROOM 2C02,BETHESDA,MD 20892, USA. NR 148 TC 39 Z9 39 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 J9 PROG BRAIN RES JI Prog. Brain Res. PY 1992 VL 90 BP 107 EP 131 PG 25 WC Neurosciences SC Neurosciences & Neurology GA HZ709 UT WOS:A1992HZ70900006 PM 1631297 ER PT J AU LAWSON, WB ROY, S PARENT, M HERRERA, J KARSON, C BIGELOW, L AF LAWSON, WB ROY, S PARENT, M HERRERA, J KARSON, C BIGELOW, L TI FLUID INTAKE PATTERNS IN SCHIZOPHRENIA AND NORMAL CONTROLS SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE CREATININE; DRINKING PATTERN; HYPONATREMIA; POLYDIPSIA; PSYCHOPATHOLOGY; SCHIZOPHRENIA; WATER INTOXICATION ID HYPONATREMIA; POLYDIPSIA; PSYCHOSIS AB 1. Patterns of fluid intake and unne output was examined in schizophrenia and normal controls. 2. Fluid intake and urine output were significantly higher in schizophrenic patients. 3. Bouts of drinking correlated significantly with fluid intake but did not differ significantly between schizophrenic patients and normal controls. 4. Schizophrenic patients drink more per bout compared to normal controls. C1 VANDERBILT UNIV,MED CTR,DEPT PSYCHIAT,NASHVILLE,TN 37240. METROPOLITAN STATE HOSP,NORWALK,CA. CUNY MT SINAI SCH MED,NEW YORK,NY 10029. VET ADM MED CTR,PSYCHIAT SERV,N LITTLE ROCK,AR. ST ELIZABETH HOSP,NIMH,WASHINGTON,DC 20032. OI Lawson, William/0000-0002-9324-7090 NR 12 TC 5 Z9 5 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD JAN PY 1992 VL 16 IS 1 BP 39 EP 44 DI 10.1016/0278-5846(92)90006-Z PG 6 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA HB421 UT WOS:A1992HB42100005 PM 1557505 ER PT J AU STANFIELD, BB AF STANFIELD, BB TI THE DEVELOPMENT OF THE CORTICOSPINAL PROJECTION SO PROGRESS IN NEUROBIOLOGY LA English DT Article ID RAT PYRAMIDAL TRACT; NORTH-AMERICAN OPOSSUM; SOMATIC SENSORY CORTEX; CENTRAL NERVOUS-SYSTEM; SELECTIVE COLLATERAL ELIMINATION; EARLY POSTNATAL-DEVELOPMENT; OCCIPITAL CORTICAL-NEURONS; CELL-ADHESION MOLECULE-L1; MEDIATED GENE-TRANSFER; CERVICAL SPINAL-CORD RP STANFIELD, BB (reprint author), NATL INST HLTH ANIM CTR,NIMH,NEUROPHYSIOL LAB,POB 289,POOLESVILLE,MD 20837, USA. NR 213 TC 113 Z9 113 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PY 1992 VL 38 IS 2 BP 169 EP 202 DI 10.1016/0301-0082(92)90039-H PG 34 WC Neurosciences SC Neurosciences & Neurology GA GU698 UT WOS:A1992GU69800002 PM 1546163 ER PT J AU PACIOTTI, GF BARON, D LICINIO, J TAMARKIN, L WONG, ML GOLD, PW ALTEMUS, ME RUBINOW, D AF PACIOTTI, GF BARON, D LICINIO, J TAMARKIN, L WONG, ML GOLD, PW ALTEMUS, ME RUBINOW, D TI NOVEL ENZYME IMMUNOASSAYS FOR THE DETECTION OF THE CYTOKINES INTERLEUKIN-1-ALPHA AND INTERLEUKIN-2 IN THE CIRCULATION OF NORMAL SUBJECTS - 24-HOUR PROFILES SO PROGRESS IN NEUROENDOCRINIMMUNOLOGY LA English DT Article ID PLASMA; CELLS; PROLIFERATION; HORMONES; RECEPTOR; INVITRO; GENE AB Twenty-four-h profiles of circulating IL-1-alpha and IL-2 were determined in normal volunteers by a novel set of enzyme immunoassays. Each assay was validated by studies of serum parallelism, quantitative recovery and the immunoreactivity of HPLC-fractionated cytokine-containing serum. Samples taken from 3 normal female subjects demonstrated that IL-1-alpha and IL-2 occur endogenously and that hourly mean IL-1-alpha levels range from 0.5 to 3 ng/ml, whereas hourly mean IL-2 levels range from 2 to 14 ng/ml. Blood sampling every 15 min for 24 h indicated that levels of IL-1-alpha and IL-2 do not remain constant throughout the day. C1 NIMH,NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. RP PACIOTTI, GF (reprint author), ASSAY RES INC,BLDG 335,PAINT BRANCH DR,COLLEGE PK,MD 20742, USA. RI Wong, Ma-Li/D-7903-2011; Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 24 TC 22 Z9 22 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 1045-2001 J9 PROG NEUROENDOCRINIM PY 1992 VL 5 IS 1 BP 21 EP 30 PG 10 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA HR668 UT WOS:A1992HR66800003 ER PT J AU BAND, LC PERT, A WILLIAMS, W DECOSTA, BR RICE, KC WEBER, RJ AF BAND, LC PERT, A WILLIAMS, W DECOSTA, BR RICE, KC WEBER, RJ TI CENTRAL MU-OPIOID RECEPTORS MEDIATE SUPPRESSION OF NATURAL-KILLER ACTIVITY INVIVO SO PROGRESS IN NEUROENDOCRINIMMUNOLOGY LA English DT Article ID MORPHINE; STRESS; MICE; INVOLVEMENT; INHIBITION; RELEASE; RATS AB The CNS opioid receptor subtypes responsible for opioid effects on natural killer (NK) cytotoxicity were examined by microinjecting opioid receptor-selective agonists into the lateral ventricles (i.c.v.) of Fischer 344N rats. Dose ranges of 20-200 nmol (-)-(1S,2S)-U50,488 and 60-200 nmol [D-Pen2,5]-Enkephalin (DPDPE), selective for kappa and delta receptors, respectively, did not affect NK cytotoxic activity; however, the lowest DPDPE dose, 20 nmol, increased NK cytotoxicity. In contrast, 60-200 nmol of the selective mu agonist [D-Ala2, NMe-Phe4, Gly-ol]-Enkephalin (DAGO) reduced NK activity. This reduction was blocked by pretreatment with naltrexone (5 mg/kg, i.p.). These findings indicate that opioid-induced immunosuppression is mediated primarily through central mu receptors. DAGO (60 nmol) had no effect on plasma corticosterone or ACTH levels, suggesting that central mu binding does not reduce NK activity through activation of the hypothalamic-pituitary-adrenal-axis. C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. RP BAND, LC (reprint author), NIDDKD,MED CHEM LAB,NEUROIMMUNOL UNIT,BLDG 8,RM 111,N100K,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 31 TC 37 Z9 37 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 1045-2001 J9 PROG NEUROENDOCRINIM PY 1992 VL 5 IS 2 BP 95 EP 101 PG 7 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA JD351 UT WOS:A1992JD35100002 ER PT J AU PURI, J PIERCE, JH HOFFMAN, T AF PURI, J PIERCE, JH HOFFMAN, T TI TRANSDUCTION OF A SIGNAL FOR ARACHIDONIC-ACID METABOLISM BY UNTRIGGERED CSF-1 RECEPTOR INDUCES AN OPPOSITE EFFECT TO THAT INDUCED BY CSF-1 RECEPTOR AND ITS LIGAND - SEPARATE REGULATION OF PHOSPHOLIPASE-A2 AND CYCLOOXYGENASE BY CSF-1 RECEPTOR CSF-1 SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article ID TYROSINE KINASE SUBSTRATE; STIMULATING FACTOR CSF-1; GROWTH-FACTOR; PROTEIN-KINASE; 4-HYDROXYCINNAMAMIDE DERIVATIVES; A-431 CELLS; FACTOR-I; INHIBITORS; PHOSPHORYLATION; ONCOGENE AB The mouse hematopoietic cell line, 32D, was transfected with c-fms, which encodes for the CSF-1 receptor, a tyrosine kinase (TK). In the absence of CSF-1, transfected cells show moderate levels of arachidonic acid (AA) release and produce a substantial amount of prostaglandin E2 (PGE2) in comparison with the original cell line. Exposure of transfected cells to CSF-1, while inducing a substantial increase in arachidonate release, nevertheless resulted in inhibition of PGE2 production. Addition of ST638, a tyrosine kinase inhibitor, to cells transfected with c-fms in the absence of CSF-1 inhibited PGE2 production within 10-60 min. Its addition to the same cells in the presence of CSF-1 induced an opposite effect, but required longer treatment (24 h). In either cell type, AA release was not affected by this agent. These data indicate that CSF-1 may regulate cyclooxygenase activity. The different effect of CSF-1 receptor on PGE2 production in the presence or absence of CSF-1 and the opposite effect of a tyrosine kinase inhibitor on PGE2 suggest that both the receptor alone or the receptor-ligand complex may transduce an active, but different, signal through tyrosine phosphorylation. CSF-1 receptor and CSF-1 may exert separate, but related, effects on phospholipase A2 and cyclooxygenase activity which, in concert, or along with other tyrosine kinases, regulate prostaglandin production. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,CELL BIOL LAB,HFB 450,BLDG 29,ROOM 225,BETHESDA,MD 20892. NCI,CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. NR 30 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD JAN PY 1992 VL 45 IS 1 BP 43 EP 48 DI 10.1016/0952-3278(92)90101-N PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA GZ138 UT WOS:A1992GZ13800005 PM 1532099 ER PT J AU THOMPSON, MP FARRELL, HM MOHANAM, S LIU, S KIDWELL, WR BANSAL, MP COOK, RG MEDINA, D KOTTS, CE BANO, M AF THOMPSON, MP FARRELL, HM MOHANAM, S LIU, S KIDWELL, WR BANSAL, MP COOK, RG MEDINA, D KOTTS, CE BANO, M TI IDENTIFICATION OF HUMAN-MILK ALPHA-LACTALBUMIN AS A CELL-GROWTH INHIBITOR SO PROTOPLASMA LA English DT Article ID CALCIUM-BINDING; CULTURE MEDIA; MAMMARY CELLS; PROTEIN; TISSUE; ELECTROPHORESIS; PURIFICATION; QUANTITIES; REGULATOR; SEQUENCE AB A growth inhibitory protein, mammary inhibitory activity (MIA), was purified to apparent homogeneity from human milk. At concentrations of 5 to 10 ng/ml, the factor inhibited the growth of mammary epithelial cells by 30-80% and also inhibited the growth of normal rat kidney cells. Whereas the cell division of normal human mammary epithelium in primary culture was inhibited by MIA, cell division by fibroblasts from the same tissues was unresponsive. Inhibition was dose and time dependent and readily reversed when MIA was removed. MIA also inhibited growth in culture for three cell lines. The growth inhibitory protein migrated as a 14 kDa protein under reducing conditions on polyacrylamide gels in the presence of sodium dodecyl sulfate. The apparent isoelectric point was pI 5.0. The amino acid composition of MIA resembled that of alpha-lactalbumin, and sequence analysis of the N-terminal region comprising residues 1-24 and an isolated peptide were identical with the N-terminal and residues 66-81 of human alpha-lactalbumin. In addition, MIA was active in the lactose synthase system. The results strongly suggest that MIA and alpha-lactalbumin are identical proteins. Consistent with these results, alpha-lactalbumin preparations from several mammalian species, including human, goat, cow and camel, were all found to be growth inhibitory for cultured mammary epithelial cells. The inhibitory activity associated with human alpha-lactalbumin was destroyed by digestion with pepsin or chymotrypsin, by carboxymethylation of cysteine, or by cleavage of methionine 90 following cyanogen bromide treatment. The results raise the possibility that during lactation alpha-lactalbumin, a product of mammary cell differentiation, could be a physiologically relevant feed-back inhibitor of mammary cell growth and perhaps of other cell types as well. C1 USDA ARS,EASTERN REG RES CTR,600 E MERMAID LANE,PHILADELPHIA,PA 19118. MADURAI KAMARAJ UNIV,SCH BIOL SCI,DIV CANC BIOL,MADURAI 625021,TAMIL NADU,INDIA. NCI,SURG BRANCH,BETHESDA,MD 20892. CELLCO ADV BIOREACTORS INC,KENSINGTON,MD. BAYLOR COLL MED,HOWARD HUGHES MED INST,HOUSTON,TX 77030. GENENTECH INC,DEPT MED & ANALYT CHEM,SAN FRANCISCO,CA 94080. BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MICROBIOL & IMMUNOL,HOUSTON,TX 77030. GEORGETOWN UNIV,LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. NR 47 TC 27 Z9 27 U1 0 U2 3 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0033-183X J9 PROTOPLASMA JI Protoplasma PY 1992 VL 167 IS 3-4 BP 134 EP 144 DI 10.1007/BF01403376 PG 11 WC Plant Sciences; Cell Biology SC Plant Sciences; Cell Biology GA HW446 UT WOS:A1992HW44600002 ER PT J AU PUTNAM, FW AF PUTNAM, FW TI ARE ALTER PERSONALITIES FRAGMENTS OR FIGMENTS - DISCUSSION SO PSYCHOANALYTIC INQUIRY LA English DT Article; Proceedings Paper CT SYMP ON VIEWPOINTS ON MULTIPLE PERSONALITY DISORDER, HELD AS THE 25TH ANNUAL SCIENTIFIC DAY PROGRAM OF THE SHEPPARD AND ENOCH PRATT HOSPITAL CY APR 21, 1990 CL BALTIMORE, MD SP SHEPPARD & ENOCH PRATT HOSP ID DISORDER RP PUTNAM, FW (reprint author), NIMH,DEV PSYCHOL LAB,DISSOCIAT DISORDERS UNIT,BETHESDA,MD 20892, USA. NR 11 TC 27 Z9 27 U1 0 U2 2 PU ANALYTIC PRESS PI HILLSDALE PA 365 BROADWAY, HILLSDALE, NJ 07642 SN 0735-1690 J9 PSYCHOANAL INQ JI Psychoanal. Inq. PY 1992 VL 12 IS 1 BP 95 EP 111 PG 17 WC Psychology, Psychoanalysis SC Psychology GA HA534 UT WOS:A1992HA53400005 ER PT J AU BLOOM, JR KESSLER, LG PEE, D AF BLOOM, JR KESSLER, LG PEE, D TI PSYCHOSOCIAL ASSESSMENT OF THE RECOVERY FROM MASTECTOMY - A COMPARISON OF STATIC AND DYNAMIC MODELING SO PSYCHOLOGY & HEALTH LA English DT Article DE PSYCHOSOCIAL ASSESSMENT; CHRONIC DISEASE; MASTECTOMY; BREAST CANCER; PSYCHOLOGICAL FUNCTIONING; PSYCHOSOCIAL MORBIDITY FROM CANCER ID BREAST-CANCER; PRIMARY CARE; IMPACT AB The psychosocial functioning of women during the year following surgery for breast cancer was compared to women who had surgery for gall bladder disease, a negative breast biopsy or no surgery. An index measuring psychological functioning was developed from a battery of commonly used self report measures. Results indicated that relative to the non-surgical group, all three surgical groups had poorer psychological functioning after surgery; all but the mastectomy group were indistinguishable one year later. These findings are due to a lack of difference in rates of recovery; the dynamic model replicates the static model generally used in analyses of the impact of disease and its treatment. The results suggest that psychological intervention may continue to be important as time post-surgery increases when the immediate trauma has lessened as well as soon after surgery. C1 UNIV CALIF BERKELEY,BERKELEY,CA 94720. NCI,BETHESDA,MD 20892. NR 40 TC 2 Z9 2 U1 1 U2 1 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 0887-0446 J9 PSYCHOL HEALTH JI Psychol. Health PY 1992 VL 7 IS 2 BP 131 EP 146 DI 10.1080/08870449208520015 PG 16 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary SC Public, Environmental & Occupational Health; Psychology GA KB938 UT WOS:A1992KB93800004 ER PT J AU BLAINE, JD LING, W AF BLAINE, JD LING, W TI PSYCHOPHARMACOLOGICAL TREATMENT OF COCAINE DEPENDENCE SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article; Proceedings Paper CT 31ST ANNUAL MEETING OF THE NEW CLINICAL DRUG EVALUATION UNIT CY MAY 28-31, 1991 CL KEY BISCAYNE, FL SP NEW CLIN DRUG EVALUAT UNIT, NIMH, DIV CLIN RES C1 LOS ANGELES ADDICT TREATMENT RES CTR,LOS ANGELES,CA. RP BLAINE, JD (reprint author), NATL INST DRUG ABUSE,ROCKVILLE,MD, USA. NR 6 TC 11 Z9 11 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1992 VL 28 IS 1 BP 11 EP 14 PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA HX589 UT WOS:A1992HX58900004 PM 1609036 ER PT J AU JENKINS, SW WARFIELD, NA BLAINE, JD CORNISH, J LING, W ROSEN, MI URSCHEL, H WESSON, D ZIEDONIS, D AF JENKINS, SW WARFIELD, NA BLAINE, JD CORNISH, J LING, W ROSEN, MI URSCHEL, H WESSON, D ZIEDONIS, D TI A PILOT TRIAL OF GEPIRONE VS PLACEBO IN THE TREATMENT OF COCAINE DEPENDENCY SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article; Proceedings Paper CT 31ST ANNUAL MEETING OF THE NEW CLINICAL DRUG EVALUATION UNIT CY MAY 28-31, 1991 CL KEY BISCAYNE, FL SP NEW CLIN DRUG EVALUAT UNIT, NIMH, DIV CLIN RES ID ABUSE; BUSPIRONE; DESIPRAMINE; SEVERITY AB An interim analysis of 41 evaluable patients compared gepirone to placebo treatment in a randomized, double-blind, 12-week study of cocaine dependence without opiate abuse. The response to gepirone at a mean dose of 16.25 mg/day did not differ from placebo by measures of time in study, positive urine cocaine screens (> 6 weeks), Clinical Global Impressions (CGI) Global Improvements Scale, Cocaine Craving Scale (CCS), Quantitative Cocaine Inventory (QCI), Addition Severity Index (ASI), Global Assessment Scale (GAS), Hamilton Rating Scale for Depression (HAM-D), and Hamilton Anxiety Scale (HAM-A). Both treatment groups showed similar modest, average improvements during the study in all treatment measures. Adverse events were not treatment limiting. The following demographic and study measures suggested favorable trends for study outcomes: older age, divorced status, higher pre-treatment cocaine use, lower CCS scores, and lower self-reports of cocaine use according to QCI. C1 UNIV PENN,SCH MED,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. NATL INST DRUG ABUSE,TREATMENT RES BRANCH,ROCKVILLE,MD. LOS ANGELES ADDICT TREATMENT RES CTR,LOS ANGELES,CA. YALE UNIV,SCH MED,DEPT PSYCHIAT,NEW HAVEN,CT 06510. RP JENKINS, SW (reprint author), BRISTOL MYERS SQUIBB,PHARMACEUT RES INST,POB 5100,CNS-402,WALLINGFORD,CT 06492, USA. NR 28 TC 14 Z9 14 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1992 VL 28 IS 1 BP 21 EP 26 PG 6 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA HX589 UT WOS:A1992HX58900006 PM 1609038 ER PT J AU RUDORFER, MV AF RUDORFER, MV TI MONOAMINE-OXIDASE INHIBITORS - REVERSIBLE AND IRREVERSIBLE SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article; Proceedings Paper CT 31ST ANNUAL MEETING OF THE NEW CLINICAL DRUG EVALUATION UNIT CY MAY 28-31, 1991 CL KEY BISCAYNE, FL SP NEW CLIN DRUG EVALUAT UNIT, NIMH, DIV CLIN RES ID PRESSOR SENSITIVITY CHANGES; ELDERLY DEPRESSED-PATIENTS; PLATELET MAO INHIBITION; ATYPICAL DEPRESSION; L-DEPRENYL; TRICYCLIC ANTIDEPRESSANTS; REFRACTORY DEPRESSION; CLINICAL-PHARMACOLOGY; RESISTANT DEPRESSION; HEALTHY-VOLUNTEERS AB Coincident with and in part fueling advances in diagnostic nosology and drug development, the recent resurgence of interest in monoamine oxidase inhibitors (MAOIs) is reviewed. Accidentally discovered nearly 40 years ago as the first true antidepressants, the MAOIs soon fell into disfavor due to concerns about toxicity and seemingly lesser efficacy compared with the newer tricyclic compounds. Now that we have better understanding of the nature of the hypertensive and hyperpyrexic interactions of MAOIs with other substances, these medications have assumed a role in the treatment of nonendogenous depressive and anxiety syndromes, especially in operationally defined "atypical depression." The discovery of two MAO isoenzymes has resulted in a new generation of selective inhibitors in the search for enhanced efficacy (i.e., clorgyline) or safety (i.e., l-deprenyl). Most promising is the emerging class of reversible selective MAO-type A inhibitors, such as moclobemide, which combine antidepressant potency with freedom from the risk of dangerous tyramine-type adverse interactions. RP RUDORFER, MV (reprint author), NIMH,DIV CLIN RES,CLIN TREATMENT RES BRANCH,5600 FISHERS LANE,ROOM 10C-26,ROCKVILLE,MD 20857, USA. NR 109 TC 21 Z9 21 U1 5 U2 6 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1992 VL 28 IS 1 BP 45 EP 57 PG 13 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA HX589 UT WOS:A1992HX58900009 PM 1609042 ER PT J AU LEBOWITZ, BD AF LEBOWITZ, BD TI DEVELOPMENTS IN TREATMENT OF ALZHEIMERS-DISEASE SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article; Proceedings Paper CT 31ST ANNUAL MEETING OF THE NEW CLINICAL DRUG EVALUATION UNIT CY MAY 28-31, 1991 CL KEY BISCAYNE, FL SP NEW CLIN DRUG EVALUAT UNIT, NIMH, DIV CLIN RES RP LEBOWITZ, BD (reprint author), NIMH,ROCKVILLE,MD 20857, USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1992 VL 28 IS 1 BP 59 EP 60 PG 2 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA HX589 UT WOS:A1992HX58900010 PM 1609043 ER PT J AU KENNEDY, NJ SANBORN, JS AF KENNEDY, NJ SANBORN, JS TI DISCLOSURE OF TARDIVE-DYSKINESIA - EFFECT OF WRITTEN POLICY ON RISK DISCLOSURE SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article; Proceedings Paper CT 31ST ANNUAL MEETING OF THE NEW CLINICAL DRUG EVALUATION UNIT CY MAY 28-31, 1991 CL KEY BISCAYNE, FL SP NEW CLIN DRUG EVALUAT UNIT, NIMH, DIV CLIN RES AB Over half of the states in the country have written statutory and/or regulatory policies that require psychiatrists treating inpatients within the state mental health system to disclose risks associated with treatment to voluntarily admitted patients. A severe side effect associated with the long-term use of neuroleptic medication is tardive dyskinesia (TD). A nationwide study was conducted to investigate the effect of written risk disclosure policy on psychiatrists' self-reported disclosure of the risks associated with neuroleptics to individuals diagnosed as having schizophrenia of a chronic nature. Participating in the study were 520 psychiatrists from 94 state/county mental hospitals located in 35 states. Fifty-four percent of those psychiatrists reported that they typically disclosed TD to the target patient population. The study results did not support the hypothesis that the presence of statutory and regulatory policy on disclosure of risk results in psychiatrists typically disclosing TD to patients. RP KENNEDY, NJ (reprint author), NIDA,DIV EPIDEMIOL & PREVENT RES,5600 FISHERS LANE,ROCKWALL II,SUITE 615,ROCKVILLE,MD 20857, USA. NR 13 TC 6 Z9 6 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1992 VL 28 IS 1 BP 93 EP 100 PG 8 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA HX589 UT WOS:A1992HX58900016 PM 1351688 ER PT J AU WEINGARTNER, H ECKARDT, M MOLCHAN, S SUNDERLAND, T WOLKOWITZ, O AF WEINGARTNER, H ECKARDT, M MOLCHAN, S SUNDERLAND, T WOLKOWITZ, O TI MEASUREMENT AND INTERPRETATION OF CHANGES IN MEMORY IN RESPONSE TO DRUG TREATMENTS SO PSYCHOPHARMACOLOGY BULLETIN LA English DT Article ID BENZODIAZEPINE RECEPTORS; ALZHEIMERS-DISEASE; IMPLICIT MEMORY; DIAZEPAM; SYSTEMS; METAMEMORY; AMNESIA; DISSOCIATION; ANTAGONISM; LORAZEPAM AB Drug-induced changes in cognitive functions such as memory are generally domain specific rather than general effects, that is, only some components of memory are altered. Changes in memory can be secondary to alterations in other cognitive domains such as attention, or non-cognitive domains (mood and arousal), or the direct result of alterations on those neurobiological systems that determine memory functions. The selective memory impairing effects of benzodiazepines are used to illustrate how cognitive neuroscience methods and theory can be useful in assessing the memory changes produced by psychoactive drugs. C1 NIMH,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DEPT PSYCHIAT,SAN FRANCISCO,CA 94143. RP WEINGARTNER, H (reprint author), NIAAA,LCS,COGNIT NEUROSCI SECT,BLDG 10,ROOM 3B19,BETHESDA,MD 20892, USA. NR 56 TC 18 Z9 18 U1 8 U2 8 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0048-5764 J9 PSYCHOPHARMACOL BULL JI Psychopharmacol. Bull. PY 1992 VL 28 IS 4 BP 331 EP 340 PG 10 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA KN743 UT WOS:A1992KN74300002 PM 1296214 ER PT J AU RIGGIN, LJC GRASSO, PG WESTCOTT, ML AF RIGGIN, LJC GRASSO, PG WESTCOTT, ML TI A FRAMEWORK FOR EVALUATING HOUSING AND COMMUNITY-DEVELOPMENT PARTNERSHIP PROJECTS SO PUBLIC ADMINISTRATION REVIEW LA English DT Article AB Can public-private partnerships be effectively evaluated? Leslie Riggin, Patrick Grasso, and Mary Westcott turned their attention to this issue in an effort by the General Accounting Office to deal with the unique challenges posed by housing and community development programs which make considerable use of these partnerships. In this article, they discuss the major obstacles to assessing the work of the partnerships and provide a framework based on nine criteria reflecting three standards: needs, process, and outcomes. C1 NIDA,LEXINGTON,KY 40583. RP RIGGIN, LJC (reprint author), US GEN ACCOUNTING OFF,DIV PROGRAM EVALUAT & METHODOL,WASHINGTON,DC 20548, USA. NR 16 TC 3 Z9 3 U1 1 U2 6 PU AMER SOC PUBLIC ADMIN PI WASHINGTON PA 1120 G STREET WASHINGTON, DC 20005 SN 0033-3352 J9 PUBLIC ADMIN REV JI Public Adm. Rev. PD JAN-FEB PY 1992 VL 52 IS 1 BP 40 EP 46 DI 10.2307/976544 PG 7 WC Public Administration SC Public Administration GA GW801 UT WOS:A1992GW80100006 ER PT J AU LESHNER, AI AF LESHNER, AI TI PANIC DISORDER - A NATIONAL PROBLEM, A FEDERAL RESPONSE SO PUBLIC HEALTH REPORTS LA English DT Editorial Material RP LESHNER, AI (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JAN-FEB PY 1992 VL 107 IS 1 BP 1 EP 2 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA HD642 UT WOS:A1992HD64200001 PM 1738798 ER PT J AU NOVELLO, AC DEGRAW, C KLEINMAN, DV AF NOVELLO, AC DEGRAW, C KLEINMAN, DV TI HEALTHY-CHILDREN READY TO LEARN - AN ESSENTIAL COLLABORATION BETWEEN HEALTH AND EDUCATION SO PUBLIC HEALTH REPORTS LA English DT Article AB The "Healthy Children Ready to Learn" initiative starts with the underlying concept that health is a critical partner to optimum education. All children have a right to be healthy. At a minimum, this right assumes promoting optimum use of available and effective preventive measures, such as ensuring compliance with immunization recommendations; promoting measures to prevent injuries; ensuring opportunities to identify disease and disabilities early; and providing prompt treatment when needed. Families must receive the support and assistance they need to raise healthy and educated children. Activities directed toward National Education Goals and the related National Health Promotion and Disease Prevention Objectives can advance progress toward school readiness, focus attention and available resources on needed programs and services, and thus help the nation in achieving its goal of having all children arriving at school each day healthy, well nourished, and ready to learn. To realize these goals and objectives, the two critical systems of greatest importance to children, those providing health services and education, need to collaborate, not only among themselves, but also with social services. A range of critical health problems will require our attention if the goals are to be met, such as availability of prenatal care, infant mortality, inadequate nutrition during pregnancy or early childhood, or both, disease prevention by immunization, infants who have been exposed to drugs, fetal alcohol syndrome, and the emotional and mental disorders of early childhood, to name a few. At any one time, any family may be in need of appropriate services. To address the health and well-being of their young children, a continuum of appropriate, accessible services must be available in the community. The first steps toward successful achievement of the readiness goal will require the identification of health, education, and social service programs that serve young children and their families, and the creation of a climate that fosters innovative and effective collaboration between programs at the Federal and State levels, especially as it pertains to the community. Policies and programs should be built around the needs of families. In this regard, the critical role that parents play in shaping a healthy environment conducive to school readiness must be recognized as a key element in shaping the strategies that should help in achieving the readiness goal. Similarly important is the need to engage professional organizations and other private sector groups involved with health, education, and other children's issues to work with government and families to achieve the school readiness goal and its related health objectives. C1 NIDR,NATL CARIES PROGRAM,BETHESDA,MD 20892. RP NOVELLO, AC (reprint author), OFF ASSISTANT SECRETARY HLTH,OFF PUBL AFFAIRS,OFF DIS PREVENT & HLTH PROMOT,WASHINGTON,DC 20201, USA. FU NIDA NIH HHS [T32 DA019426]; NIMHD NIH HHS [RC2 MD004803] NR 25 TC 29 Z9 32 U1 0 U2 8 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 JAN-FEB PY 1992 VL 107 IS 1 BP 3 EP 15 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA HD642 UT WOS:A1992HD64200002 PM 1738805 ER PT J AU MEISSNER, HI BERGNER, L MARCONI, KM AF MEISSNER, HI BERGNER, L MARCONI, KM TI DEVELOPING CANCER CONTROL CAPACITY IN STATE AND LOCAL PUBLIC-HEALTH AGENCIES SO PUBLIC HEALTH REPORTS LA English DT Article AB In 1986, the National Cancer Institute began a major grant program to enhance the technical capabilities of public health departments in cancer prevention and control. This effort, commonly referred to as "capacity building" for cancer control, provided funding to support eight State and one local health department. The program focused on developing the knowledge and skills of health department personnel to implement intervention programs in such areas as smoking cessation, diet modification, and breast and cervical cancer screening. The grants ranged from 2 to 5 years in length, with funding of $125,000 to $1.6 million per grant. The total for the program was $7.4 million. While the priorities set for these grants were nominally similar, their capacity building activities in cancer prevention and control evolved into unique interventions reflecting the individual needs and priorities of each State or locality. Their experiences illustrate that technical development for planning, implementing, and evaluating cancer prevention and control programs is a complex process that must occur at multiple levels, regardless of overall approach. Factors found to contribute to successful implementation of technical development programs include commitment of the organization's leadership to provide adequate support for staff and activities and to keep cancer prevention and control on the organizational agenda, the existence of appropriate data to monitor and evaluate programs, appropriately trained staff, building linkages with State and community agencies and coalitions to guide community action, an established plan or process for achieving cancer control objectives, access to the advice of and participation of individual cancer and health experts, an informed State legislature, diffusion of cancer prevention and control efforts, and the ability to obtain funds needed for future activities. RP MEISSNER, HI (reprint author), NCI,DIV CANC PREVENT & CONTROL,PUBL HLTH APPLICAT RES BRANCH,BETHESDA,MD 20892, USA. NR 5 TC 20 Z9 20 U1 0 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 JAN-FEB PY 1992 VL 107 IS 1 BP 15 EP 23 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA HD642 UT WOS:A1992HD64200003 PM 1738803 ER PT J AU VANDERLINDEN, C AF VANDERLINDEN, C TI NIMH PANIC DISORDER CAMPAIGN FOCUSES ON RECOGNITION, TREATMENT SO PUBLIC HEALTH REPORTS LA English DT Article RP VANDERLINDEN, C (reprint author), NIMH,OFF SCI INFORMAT,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JAN-FEB PY 1992 VL 107 IS 1 BP 129 EP 129 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA HD642 UT WOS:A1992HD64200021 ER PT J AU KWOCK, L GILL, M MCMURRY, HL BECKMAN, W RALEIGH, JA JOSEPH, AP AF KWOCK, L GILL, M MCMURRY, HL BECKMAN, W RALEIGH, JA JOSEPH, AP TI EVALUATION OF A FLUORINATED 2-NITROIMIDAZOLE BINDING TO HYPOXIC CELLS IN TUMOR-BEARING RATS BY F-19 MAGNETIC-RESONANCE SPECTROSCOPY AND IMMUNOHISTOCHEMISTRY SO RADIATION RESEARCH LA English DT Article ID P-31 NMR-SPECTROSCOPY; INVIVO; MISONIDAZOLE; RETENTION; MARKERS; PROBES; SIZE C1 UNIV N CAROLINA,CURRICULUM BIOMED ENGN,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT RADIAT ONCOL,CHAPEL HILL,NC 27599. NIEHS,RES TRIANGLE PK,NC 27709. OTSUKA ELECTR USA,FT COLLINS,CO 80525. RP KWOCK, L (reprint author), UNIV N CAROLINA,DEPT RADIOL,CHAPEL HILL,NC 27599, USA. FU NCI NIH HHS [R01 CA 39633] NR 34 TC 24 Z9 24 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JAN PY 1992 VL 129 IS 1 BP 71 EP 78 DI 10.2307/3577905 PG 8 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA GY320 UT WOS:A1992GY32000009 PM 1728059 ER PT J AU ACKERMAN, MJ AF ACKERMAN, MJ TI THE VIDEODISC IN MEDICAL-EDUCATION SO RADIOGRAPHICS LA English DT Editorial Material DE EDITORIALS; EDUCATION; IMAGES, DISPLAY; RADIOLOGY AND RADIOLOGISTS; VIDEO SYSTEMS RP ACKERMAN, MJ (reprint author), NATL LIB MED,LISTER HILL NATL CTR BIOMED COMMUNICAT,EDUCAT TECHNOL BRANCH,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 0 TC 2 Z9 2 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 JAN PY 1992 VL 12 IS 1 BP 121 EP 122 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA GZ799 UT WOS:A1992GZ79900016 PM 1734457 ER PT J AU FEUERSTEIN, IM JICHA, DL PASS, HI CHOW, CK CHANG, R LING, A HILL, SC DWYER, AJ TRAVIS, WD HOROWITZ, ME STEINBERG, SM FRANK, JA DOPPMAN, JL AF FEUERSTEIN, IM JICHA, DL PASS, HI CHOW, CK CHANG, R LING, A HILL, SC DWYER, AJ TRAVIS, WD HOROWITZ, ME STEINBERG, SM FRANK, JA DOPPMAN, JL TI PULMONARY METASTASES - MR IMAGING WITH SURGICAL CORRELATION - A PROSPECTIVE-STUDY SO RADIOLOGY LA English DT Article DE LUNG NEOPLASMS, CT; LUNG NEOPLASMS, DIAGNOSIS; LUNG NEOPLASMS, MR; LUNG NEOPLASMS, SECONDARY; LUNG, NODULE; MAGNETIC RESONANCE (MR), COMPARATIVE STUDIES ID COMPUTED-TOMOGRAPHY; MAGNETIC-RESONANCE; CHEST; SEQUENCE; NODULES; THORAX; CT AB The sensitivity of magnetic resonance (MR) imaging for detection of pulmonary metastases in 11 patients scheduled for thoracotomy and curative resection of metastases was evaluated with a prospective, controlled study. MR imaging performed at 0.5 T was compared with chest radiography, computed tomography (CT), and thoracotomy in 12 cases. (One patient had two separate occurrences of pulmonary metastases.) All images were interpreted in blinded fashion. When all MR sequences were interpreted together, MR imaging enabled correct identification of all patients with pulmonary nodules (100%). CT enabled detection of at least one nodule in all 12 cases (100%) by design; the sensitivity of chest radiography was only 64%. For individual nodules, MR imaging was at least as sensitive as CT (P2 < .25 [two-sided value]) and significantly more sensitive than chest radiography (P2 < .01). Among all MR sequences, short inversion time inversion-recovery sequences had the highest sensitivity for detection of individual nodules (82%). C1 NCI,SURG BRANCH,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT RADIOL,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,DEPT INTERNAL MED,WASHINGTON,DC 20007. RP FEUERSTEIN, IM (reprint author), NIH,DEPT DIAGNOST RADIOL,9000 ROCKVILLE PIKE,BLDG 10,RM 1C660,BETHESDA,MD 20892, USA. NR 19 TC 43 Z9 43 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 JAN PY 1992 VL 182 IS 1 BP 123 EP 129 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA GW054 UT WOS:A1992GW05400025 PM 1727274 ER PT J AU MILLER, DL DOPPMAN, JL METZ, DC MATON, PN NORTON, JA JENSEN, RT AF MILLER, DL DOPPMAN, JL METZ, DC MATON, PN NORTON, JA JENSEN, RT TI ZOLLINGER-ELLISON SYNDROME - TECHNIQUE, RESULTS, AND COMPLICATIONS OF PORTAL VENOUS SAMPLING SO RADIOLOGY LA English DT Article DE PANCREAS, ANGIOGRAPHY; PANCREAS, NEOPLASMS; VEINS, BLOOD SAMPLING; VEINS, PANCREATIC; VENOGRAPHY ID PANCREATIC VEIN CATHETERIZATION; ISLET-CELL TUMORS; ENDOCRINE TUMORS; HORMONE ASSAY; LOCALIZATION; INSULINOMAS; GASTRINOMAS; ARTERIOGRAPHY; RADIOIMMUNOASSAY; HYPERINSULINISM AB All 95 portal venous sampling (PVS) procedures performed in patients with Zollinger-Ellison syndrome in the past 10 years at the authors' institution were reviewed. It was possible to catheterize at least one branch of the pancreaticoduodenal venous arcade in all but two procedures (98%). The highest concentration of gastrin was found in a selective sample from the pancreaticoduodenal venous arcade or the transverse pancreatic vein in 56 of 91 procedures (62%). Selective sampling of pancreatic head veins yielded a gastrin gradient sufficient for localization in 60 patients (63%). Among 55 solitary sporadic gastrinomas identified at surgery, PVS allowed correct localization of the tumor in 32 (58%); if selective samples had not been obtained, only eight (15%) would have been localized (P < .0005). Sensitivity was the same for tumors in the gastrinoma triangle (64%) and the body or tail of the pancreas (60%). There were no false-positive results. The overall complication rate was 20%, but most complications were abdominal pain lasting 3 days or less. Six patients (6%) had serious complications. C1 NCI,DIV CANC TREATMENT,SURG BRANCH,BETHESDA,MD 20892. NIADDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. RP MILLER, DL (reprint author), WARREN GRANT MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BLDG 10,RM 1C660,BETHESDA,MD, USA. NR 34 TC 34 Z9 34 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 JAN PY 1992 VL 182 IS 1 BP 235 EP 241 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA GW054 UT WOS:A1992GW05400045 PM 1727289 ER PT B AU WOUDE, V HUNT HUNTER DOREE KIRSCHNER SHALLOWAY NASMYTH BEACH CROSS NIGG AF WOUDE, V HUNT HUNTER DOREE KIRSCHNER SHALLOWAY NASMYTH BEACH CROSS NIGG BE MARSH, J TI THE ROLE OF MOS IN MEIOTIC MATURATION SO REGULATION OF THE EUKARYOTIC CELL CYCLE SE CIBA FOUNDATION SYMPOSIA LA English DT Discussion CT SYMP ON REGULATION OF THE EUKARYOTIC CELL CYCLE CY JAN 21-23, 1992 CL CIBA FDN, LONDON, ENGLAND HO CIBA FDN RP WOUDE, V (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,POB B,FREDERICK,MD 21702, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA CHICHESTER BN 0-471-93446-1 J9 CIBA F SYMP PY 1992 VL 170 BP 244 EP 247 PG 4 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA BW54J UT WOS:A1992BW54J00016 ER PT J AU TREINEN, KA HEINDEL, JJ AF TREINEN, KA HEINDEL, JJ TI EVIDENCE THAT MEHP INHIBITS RAT GRANULOSA-CELL FUNCTION BY A PROTEIN-KINASE C-INDEPENDENT MECHANISM SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE GRANULOSA CELLS; MEHP; PKC; PHORBOL ESTERS; TPA; INVITRO; FEMALE REPRODUCTIVE TOXICOLOGY; RAT ID FOLLICLE-STIMULATING-HORMONE; ANGIOTENSIN-II RECEPTORS; PHTHALATE-ESTERS; SERTOLI-CELL; CYCLIC-AMP; PENTYL PHTHALATE; PRIMARY CULTURES; PHORBOL ESTERS; OVARIAN; ACTIVATION AB We have recently shown that mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of the reproductive toxicant di-(ethylhexyl) phthalate (DEHP), inhibited FSH- but not forskolin-, isoproterenol-, or cholera toxin-stimulated granulosa cell cAMP accumulation in vitro. In addition, MEHP also inhibited FSH-stimulated progesterone production, a cAMP-dependent process. Similar to MEHP, the protein kinase C (PKC) activator, 12-0-tetradecanoyl-phorbol 13-acetate (TPA) has been shown to inhibit rat granulosa cell cAMP accumulation in a FSH-specific manner, and decrease FSH-stimulated progesterone production. Due to the similarity with respect to inhibition of cAMP accumulation, we conducted studies to determine if the inhibitory actions of MEHP on granulosa cell function are mediated via activation of PKC. Treatment of granulosa cells for 48 h with 100-mu-M MEHP produced no effect on forskolin- or isoproterenol-stimulated progesterone production, indicating that MEHP does not have a post-cyclic AMP site of action with respect to progesterone inhibition. Unlike the FSH-specific effect seen with MEHP, treatment with 10 nM TPA inhibited FSH-, forskolin-, and isoproterenol-stimulated progesterone production. In addition, maximally inhibitory concentrations of TPA and MEHP caused significantly greater inhibition of FSH-stimulated cAMP accumulation than either compound alone. Finally, addition of the progesterone precursor, pregnenolone, reversed the FSH-stimulated progesterone production inhibition by MEHP, but not that by TPA. Taken together, these data indicate that the inhibitory effects of MEHP on granulosa cell function are independent of phorbol ester-sensitive PKC activation. C1 NIEHS,NATL TOXICOL PROGRAM,DEV & REPROD TOXICOL GRP,RES TRIANGLE PK,NC 27709. NR 28 TC 11 Z9 11 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PY 1992 VL 6 IS 2 BP 143 EP 148 DI 10.1016/0890-6238(92)90116-B PG 6 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA HL330 UT WOS:A1992HL33000006 PM 1317232 ER PT J AU CHAPIN, RE FILLER, RS GULATI, D HEINDEL, JJ KATZ, DF MEBUS, CA OBASAJU, F PERREAULT, SD RUSSELL, SR SCHRADER, S SLOTT, V SOKOL, RZ TOTH, G AF CHAPIN, RE FILLER, RS GULATI, D HEINDEL, JJ KATZ, DF MEBUS, CA OBASAJU, F PERREAULT, SD RUSSELL, SR SCHRADER, S SLOTT, V SOKOL, RZ TOTH, G TI METHODS FOR ASSESSING RAT SPERM MOTILITY SO REPRODUCTIVE TOXICOLOGY LA English DT Article ID COMPUTERIZED SEMEN ANALYSIS; MOVEMENT CHARACTERISTICS; SPERMATOZOA; EXPOSURE; ALBUMIN; SYSTEM; TIME AB Computer-assisted sperm analysis (CASA) systems are becoming more widely used. With this spread of technology come more data from toxicology studies, designed to determine if treatment with putative toxicants affects sperm motion parameters. While these CASA methods provide us with more ways to evaluate toxicity and thus perhaps increase our chances of successfully protecting human health, there is also a greater likelihood that different laboratories will use different methods of collecting data on sperm motility. Different systems used with different methods in different laboratories will inevitably generate data that are difficult to compare. In a prospective attempt to address this issue of comparability and limit the problems, a group of individuals using CASA systems to analyze rat sperm motility convened to discuss methodologic issues, share data, and try to reach a consensus about methods for performing these studies. This article shares those meetings and data in the hope that common methods will enhance interlaboratory comparisons. C1 AMER CYNAMID CO,DIV MED RES,PEARL RIVER,NY. ENVIRONM HLTH RES & TESTING INC,LEXINGTON,KY. UNIV CALIF DAVIS,SCH MED,DEPT OBSTET & GYNECOL,DAVIS,CA 95616. DUPONT CO,HASKELL LABS,NEWARK,DE. US EPA,RES TRIANGLE PK,NC 27711. MANTECH ENVIRONM TECHNOL SERV,RES TRIANGLE PK,NC. UNIV CALIF LOS ANGELES,LOS ANGELES CTY HARBOR MED CTR,DIV ENDOCRINOL,TORRANCE,CA 90509. ENVIRONM PROTECT AGCY,CINCINNATI,OH. NIOSH,CTR DIS CONTROL,CINCINNATI,OH 45226. RP CHAPIN, RE (reprint author), NIEHS,NATL TOXICOL PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Schrader, Steven/E-8120-2011; OI Chapin, Robert/0000-0002-5997-1261 NR 34 TC 42 Z9 42 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PY 1992 VL 6 IS 3 BP 267 EP 273 DI 10.1016/0890-6238(92)90183-T PG 7 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA HV379 UT WOS:A1992HV37900010 PM 1591485 ER PT J AU SCHRADER, SM CHAPIN, RE CLEGG, ED DAVIS, RO FOURCROY, JL KATZ, DF ROTHMANN, SA TOTH, G TURNER, TW ZINAMAN, M AF SCHRADER, SM CHAPIN, RE CLEGG, ED DAVIS, RO FOURCROY, JL KATZ, DF ROTHMANN, SA TOTH, G TURNER, TW ZINAMAN, M TI LABORATORY METHODS FOR ASSESSING HUMAN SEMEN IN EPIDEMIOLOGIC STUDIES - A CONSENSUS REPORT SO REPRODUCTIVE TOXICOLOGY LA English DT Article ID SPERM MOTILITY; INVITRO; WORKERS; MOTION C1 NATL TOXICOL PROGRAM,CINCINNATI,OH. NIEHS,RES TRIANGLE PK,NC 27709. NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC. US EPA,WASHINGTON,DC 20460. UNIV CALIF DAVIS,DEPT OBSTET & GYNECOL,DAVIS,CA 95616. US FDA,ROCKVILLE,MD 20857. CLEVELAND CLIN EDUC FDN,ANDROL LAB,CLEVELAND,OH 44106. CLEVELAND CLIN EDUC FDN,SPERM BANK,CLEVELAND,OH 44106. US EPA,CINCINNATI,OH 45268. GEORGETOWN UNIV,DEPT OBSTET & GYNECOL,WASHINGTON,DC 20007. RP SCHRADER, SM (reprint author), NIOSH,MS-C23,4676 COLUMBIA PKWY,CINCINNATI,OH 45226, USA. RI Schrader, Steven/E-8120-2011; OI Chapin, Robert/0000-0002-5997-1261 NR 25 TC 33 Z9 34 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PY 1992 VL 6 IS 3 BP 275 EP 279 DI 10.1016/0890-6238(92)90184-U PG 5 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA HV379 UT WOS:A1992HV37900011 PM 1591486 ER PT J AU RATCLIFFE, JM GLADEN, BC WILCOX, AJ HERBST, AL AF RATCLIFFE, JM GLADEN, BC WILCOX, AJ HERBST, AL TI DOES EARLY EXPOSURE TO MATERNAL SMOKING AFFECT FUTURE FERTILITY IN ADULT MALES SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE MATERNAL SMOKING; SMOKING, MALE; INFERTILITY, MALE; SEMEN QUALITY; SPERM; PRENATAL EXPOSURE, DELAYED EFFECTS; UROGENITAL DISORDERS ID PRENATAL NICOTINE EXPOSURE; SEMEN QUALITY; CIGARETTE-SMOKING; MALE-INFERTILITY; SEXUAL-BEHAVIOR; PREGNANCY; RATS; TESTOSTERONE; CONSUMPTION; ALCOHOL AB Animal data suggest that prenatal exposure to certain tobacco smoke components such as nicotine may affect the development of the male gonadal axis, which may in turn affect future adult fertility. There are no previous epidemiologic studies on the potential effects of early (prenatal and childhood) exposure to maternal smoking on the reproductive system in adult male offspring. To investigate this question, we used data from a follow-up study of reproductive function and fertility among young adult sons of mothers who had participated in a randomized clinical trial of diethylstilbestrol use during pregnancy. We observed no significant effects of early exposure to maternal smoking on conventional semen characteristics, hormone levels (follicle stimulating hormone [FSH], luteinizing hormone [LH] and testosterone), urogenital abnormalities and diseases, or perceived infertility problems. Current active smoking by the men was, however, associated with a significant decrease in the percentage of sperm with normal morphology. C1 NIEHS,BIOMATH BRANCH,DIV BIOMETRY & RISK ASSESSMENT,RES TRIANGLE PK,NC 27709. UNIV CHICAGO,CHICAGO LYING IN HOSP,DEPT OBSTET & GYNECOL,CHICAGO,IL 60637. RP RATCLIFFE, JM (reprint author), NIEHS,EPIDEMIOL BRANCH,DIV BIOMETRY & RISK ASSESSMENT,MAIL DROP A3-05,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Wilcox, Allen/0000-0002-3376-1311 NR 46 TC 30 Z9 30 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PY 1992 VL 6 IS 4 BP 297 EP 307 DI 10.1016/0890-6238(92)90192-V PG 11 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA JH055 UT WOS:A1992JH05500003 PM 1521002 ER PT J AU AHLUWALIA, B VIRMANI, M AF AHLUWALIA, B VIRMANI, M TI TEMPORAL RELATIONSHIP BETWEEN SYNAPTOSOMAL PLASMA-MEMBRANE PHOSPHORYLATION AND CONCURRENT CHANGES IN THE BEHAVIORAL PHASE DURING ETHANOL DEPENDENT INTOXICATED AND WITHDRAWAL STATE IN THE RAT SO RESEARCH COMMUNICATIONS IN SUBSTANCES OF ABUSE LA English DT Article ID BRAIN; PROTEINS; TOLERANCE; SYSTEM AB Biochemical events in the neurons are regulated by phosphorylation -dephosphorylation of synaptosomal plasma membrane (SPM) and that ethanol in dose- dependent manner affect SPM phosphorylation. The study was designed to investigate the effect of intoxication and withdrawal state on SPM phosphorylation in colliculi, hippocampus, cortex, hypothalamus, caudate and cerebellum in ethanol dependent rat. Results showed that SPM phosphorylation was significantly increased (p>0.01) in colliculi and caudate in intoxicated state. In the hippocampus and cortex during the same state there was a significant decrease (p>0 01). In hypothalamus and cerebellum SPM phosphorylation was not affected in intoxicated or in withdrawal state. Three major protein bands 12, 48 and 86 Kd were identified. The 12 and 48 Kd protein bands were more prominently than 86 Kd band. In general SPM phosphorylation in withdrawal state and controls was similar. Based on our data we conclude that in ethanol dependent rat colliculi, caudate and hippocampus are involved in intoxicated state. C1 NIAAA,PRECLIN STUDIES LAB,ROCKVILLE,MD 20855. RP AHLUWALIA, B (reprint author), HOWARD UNIV,COLL MED,DEPT OBSTET & GYNECOL,WASHINGTON,DC 20059, USA. NR 22 TC 1 Z9 1 U1 0 U2 0 PU P J D PUBLICATIONS LTD PI WESTBURY PA PO BOX 966, WESTBURY, NY 11590 SN 0193-0818 J9 RES COMMUN SUBSTANCE JI Res. Commun. Subst. Abuse PY 1992 VL 13 IS 2 BP 105 EP 121 PG 17 WC Substance Abuse SC Substance Abuse GA JH017 UT WOS:A1992JH01700003 ER PT J AU VENKATESAN, S AF VENKATESAN, S TI VIROLOGICAL AND CELLULAR PHYSIOLOGICAL ROLES OF HIV NEF PROTEIN SO RESEARCH IN VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; III HTLV-III/LAV; GTP-BINDING; MUTATIONAL ANALYSIS; ONCOGENE PRODUCT; RAS PROTEINS; TYPE-1; REPLICATION; DOMAIN; REGION RP VENKATESAN, S (reprint author), NIAID,MOLEC MICROBIOL LAB,BLDG 4,RM 328,BETHESDA,MD 20892, USA. NR 43 TC 3 Z9 3 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0923-2516 J9 RES VIROLOGY JI Res. Virol. PD JAN-FEB PY 1992 VL 143 IS 1 BP 38 EP 42 DI 10.1016/S0923-2516(06)80076-2 PG 5 WC Virology SC Virology GA HG970 UT WOS:A1992HG97000007 PM 1565853 ER PT J AU SMITHE, JA REITZ, MS AF SMITHE, JA REITZ, MS TI POINTS TO PONDER ON THE FUNCTION OF NEF SO RESEARCH IN VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; OPEN READING FRAME; IMMUNE-DEFICIENCY SYNDROME; PROTEIN; TYPE-1; EXPRESSION; REPLICATION; ANTIBODIES; SEQUENCE; PRODUCT RP SMITHE, JA (reprint author), NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 26 TC 0 Z9 1 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0923-2516 J9 RES VIROLOGY JI Res. Virol. PD JAN-FEB PY 1992 VL 143 IS 1 BP 47 EP 49 DI 10.1016/S0923-2516(06)80078-6 PG 3 WC Virology SC Virology GA HG970 UT WOS:A1992HG97000009 PM 1565855 ER PT J AU KAMINCHIK, J SARVER, N GORECKI, M PANET, A AF KAMINCHIK, J SARVER, N GORECKI, M PANET, A TI MOLECULAR CHARACTERIZATION OF HIV-1 NEF PROTEIN SO RESEARCH IN VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; NUCLEOTIDE-SEQUENCE; AIDS VIRUS; HTLV-III; PRODUCT; DOMAIN C1 NIAID,DIV AIDS,BASIC RES & DEV PROGRAM,DEV THERAPEUT BRANCH,BETHESDA,MD 20892. RP KAMINCHIK, J (reprint author), BIOTECHNOL GEN LTD,KIRYAT WEIZMANN,IL-76326 REHOVOT,ISRAEL. FU NIAID NIH HHS [N01-AI-82696] NR 11 TC 0 Z9 0 U1 0 U2 1 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0923-2516 J9 RES VIROLOGY JI Res. Virol. PD JAN-FEB PY 1992 VL 143 IS 1 BP 50 EP 52 DI 10.1016/S0923-2516(06)80079-8 PG 3 WC Virology SC Virology GA HG970 UT WOS:A1992HG97000010 PM 1565857 ER PT J AU NEBREDA, AR SEGADE, F SANTOS, E AF NEBREDA, AR SEGADE, F SANTOS, E TI THE NEF GENE-PRODUCTS - BIOCHEMICAL-PROPERTIES AND EFFECTS ON HOST-CELL FUNCTIONS SO RESEARCH IN VIROLOGY LA English DT Article ID PROTEIN; DOMAIN C1 NCI,CELLULAR & MOLEC BIOL LAB,BG 37,RM 1D28,BETHESDA,MD 20892. NR 20 TC 2 Z9 2 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0923-2516 J9 RES VIROLOGY JI Res. Virol. PD JAN-FEB PY 1992 VL 143 IS 1 BP 55 EP 59 DI 10.1016/S0923-2516(06)80081-6 PG 5 WC Virology SC Virology GA HG970 UT WOS:A1992HG97000012 PM 1565859 ER PT J AU WHITCUP, SM FENTON, RM PLUDA, JM DESMET, MD NUSSENBLATT, RB CHAN, CC AF WHITCUP, SM FENTON, RM PLUDA, JM DESMET, MD NUSSENBLATT, RB CHAN, CC TI PNEUMOCYSTIS-CARINII AND MYCOBACTERIUM AVIUM-INTRACELLULARE INFECTION OF THE CHOROID SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article AB It has been hypothesized that coinfection with mycobacteria occurs in patients with Pneumocystis carinii choroiditis, but cases demonstrating ocular infection by both organisms have not been reported. This study reports the case of a patient with P. carinii choroiditis who was treated with intravenous trimethoprim and sulfamethoxazole, followed by intravenous trimethoprim and dapsone. The choroidal lesions failed to resolve despite 6 weeks of treatment, and the patient died from massive pulmonary infection caused by P. carinii, Mycobacterium avium-intracellulare, and cytomegalovirus infections. Ocular histologic.and electron microscopic examinations revealed choroidal infection by both P. carinii and M. avium-intracellulare. Serum levels of sulfamethoxazole were below the recommended therapeutic range for treating P. carinii infection during the first week of therapy, but adequate drug levels were subsequently obtained. Failure of choroidal lesions of P. carinii to resolve in some cases may suggest insufficient antimicrobial levels in the blood or raise the possibility of coexistent M. avium-intracellulare or other opportunistic infection. RP WHITCUP, SM (reprint author), NEI,IMMUNOL LAB,BLDG 10 ROOM 10N 202,BETHESDA,MD 20892, USA. OI de Smet, Marc/0000-0002-9217-5603 NR 0 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PY 1992 VL 12 IS 4 BP 331 EP 335 PG 5 WC Ophthalmology SC Ophthalmology GA KD148 UT WOS:A1992KD14800006 PM 1485017 ER PT J AU MELNICK, RL HUFF, J AF MELNICK, RL HUFF, J TI 1,3-BUTADIENE - TOXICITY AND CARCINOGENICITY IN LABORATORY-ANIMALS AND IN HUMANS SO REVIEWS OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY LA English DT Review ID MACROCYTIC-MEGALOBLASTIC ANEMIA; NATIONAL TOXICOLOGY PROGRAM; SISTER CHROMATID EXCHANGE; SPRAGUE-DAWLEY RATS; MALE B6C3F1 MICE; INHALATION PHARMACOKINETICS; SPECIES-DIFFERENCES; BUTADIENE MONOXIDE; LIVER-MICROSOMES; MUTAGENIC ACTION RP MELNICK, RL (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 86 TC 46 Z9 46 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0179-5953 J9 REV ENVIRON CONTAM T JI Rev. Environ. Contam. Toxicol. PY 1992 VL 124 BP 111 EP 144 PG 34 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA KP859 UT WOS:A1992KP85900005 PM 1732994 ER PT J AU SHAPIRO, WR AF SHAPIRO, WR TI CHEMOTHERAPY OF MALIGNANT GLIOMAS - STUDIES OF THE BTCG SO REVUE NEUROLOGIQUE LA English DT Article; Proceedings Paper CT INTERNATIONAL MEETING ON NEUROONCOLOGY CY JUN 13-14, 1991 CL PARIS, FRANCE SP SOC FRANCAISE NEUROL ID INTRA-ARTERIAL BCNU; TUMOR COOPERATIVE GROUP; CENTRAL NERVOUS-SYSTEM; CAROTID-ARTERY; BRAIN-TUMORS; PHASE-I; POSTOPERATIVE TREATMENT; RANDOMIZED TRIAL; DRUG INFUSION; RADIOTHERAPY AB Phase III Trial 8301 tested the efficacy and safety of intraarterial (IA) BCNU for the treatment of newly resected malignant glioma, comparing IA BCNU vs intravenous (IV) BCNU (200 mg/m2 q 8 wks), each regimen without or with IV 5-FU (1 g/m2/d x 3 two wks after BCNU). All patients also received radiation therapy. 505 patients entered the study; 448 were in the Valid Study Group (VSG). Excluding 190 patients who for medical reasons were not eligible for IA BCNU, 315 patients were randomized between IA (167) and IV (148) BCNU. Actuarial analysis (logrank) demonstrated worse survival for the IA group (p = 0.002). Serious toxicity was observed in the IA group; 16 patients (9.5 %) developed irreversible encephalopathy with CT evidence of cerebral edema, and 26 patients developed visual loss ipsilateral to the infused carotid artery. 5-FU did not influence survival. Survival between the IV and the IA BCNU patients with glioblastoma multiforme did not differ, but was worse for IA BCNU patients with anaplastic astrocytoma than for IV BCNU (p = 0.002). Neuropathologically, IA BCNU produced white matter necrosis. IA BCNU is neither safe nor effective. Phase II Trial 8420, compared IA cisplatin, 60 mg/m2 every 4 wks, vs IV PCNU, 100 mg/m2 q 8 wks; 311 patients were randomized. Preliminary results have been presented. Severe encephalopathy occurred in only 1.5 % of patients receiving IA cisplatin. The median survival of the IV PCNU patients was 11.8 months; that of the IA cisplatin patients was 9.4 months, not statistically different. Current BTCG studies are: Trial 8701 randomizes newly diagnosed patients to receive (a) postoperative temporary I-125 seed implantation in the residual tumor bed, followed by standard external beam radiotherapy plus IV BCNU, or (b) external radiotherapy plus BCNU, without the seed implantation. Trial 8901 randomizes newly diagnosed patients and those previously diagnosed but not treated with chemotherapy to receive (a) standard IV BCNU, (b) combination IV BCNU plus IA cisplatin, or (c) the new agent 10-ethyl-10-deaza-aminopterin (EDAM). C1 NCI,BRAIN TUMOR COOPERAT GRP,BETHESDA,MD 20892. NR 45 TC 14 Z9 14 U1 0 U2 0 PU MASSON EDITEUR PI PARIS 06 PA 120 BLVD SAINT-GERMAIN, 75280 PARIS 06, FRANCE SN 0035-3787 J9 REV NEUROL JI Rev. Neurol. PY 1992 VL 148 IS 6-7 BP 428 EP 434 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA JF283 UT WOS:A1992JF28300007 PM 1448662 ER PT J AU QUAKYI, IA TAYLOR, DW JOHNSON, AH ALLOTEY, JB BERZOFSKY, JA MILLER, LH GOOD, MF AF QUAKYI, IA TAYLOR, DW JOHNSON, AH ALLOTEY, JB BERZOFSKY, JA MILLER, LH GOOD, MF TI DEVELOPMENT OF A MALARIA T-CELL VACCINE FOR BLOOD STAGE IMMUNITY SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article; Proceedings Paper CT 1ST AFRICAN IMMUNOLOGY MEETING OF THE INTERNATIONAL UNION OF IMMUNOLOGICAL SOCIETIES CY FEB 10-14, 1992 CL HARARE, ZIMBABWE SP INT UNION IMMUNOL SOC ID PLASMODIUM-FALCIPARUM MALARIA; CIRCUMSPOROZOITE PROTEIN; ANTIGENIC SITES; IMMUNOGENICITY; SPOROZOITES; RECOGNITION; SAFETY; MAP AB We have defined a strategy for the development of a T-cell vaccine for blood stage immunity, taking into consideration the central role of T cells and MHC restriction in malaria immune responses. We have used the AMPHI computer algorithm to identify putative T-cell epitopes from conserved regions of 11 Plasmodium falciparum asexual stage proteins. Ten of the eleven proteins are currently candidates for vaccine development. Using this algorithm we selected 22 putative T-cell epitope peptides and 8 control peptides. These peptides were used to test the T-cell responses of three defined populations of Caucasians who have (1) recovered from P. falciparum malaria, (2) been exposed, but never clinically infected, (3) never been exposed or infected. Preliminary analysis of our data shows population differences in T-cell responses to putative T-cell epitope peptides. Ultimately, these studies will help to identify those T epitopes that can be incorporated into a T-cell vaccine for protective immunity. C1 HLTH MED CTR,ROCKVILLE,MD. NIH,BETHESDA,MD 20892. QUEENSLAND INST MED RES,MOLEC IMMUNOL UNIT,HERSTON,QLD 4006,AUSTRALIA. GEORGETOWN UNIV,DEPT PEDIAT,WASHINGTON,DC 20057. RP QUAKYI, IA (reprint author), GEORGETOWN UNIV,DEPT BIOL,37TH & O ST NW,WASHINGTON,DC 20057, USA. NR 25 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PY 1992 VL 36 SU 11 BP 9 EP 16 DI 10.1111/j.1365-3083.1992.tb01611.x PG 8 WC Immunology SC Immunology GA JH283 UT WOS:A1992JH28300004 ER PT J AU HUFF, JE AF HUFF, JE TI DESIGN STRATEGIES, RESULTS AND EVALUATIONS OF LONG-TERM CHEMICAL CARCINOGENESIS STUDIES SO SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH LA English DT Article DE B6C3F1-MICE; CARCINOGENESIS; CHEMICAL CARCINOGENICITY EXPERIMENTS; FISCHER RATS; IDENTIFYING CHEMICAL CARCINOGENS; 2-YEAR BIOASSAYS ID FALSE-POSITIVE RATES; NEOPLASMS; TOXICITY; PROGRAM; GAVAGE AB Long-term toxicology and chemical carcinogenesis experiments typically involve both sexes of two species of rodents divided randomly into sets of 50-60 animals per control and exposure groups. Ordinarily three exposure concentrations are gradated down from a top level likely to show some chemically associated toxicity, but which should not compromise the normal well-being or growth and survival patterns of the animals unduly. Duration of exposure is generally two years. Single, intermittent, or varied exposures are used to mimic specific occupational or environmental situations. Exposures are started prior to conception, during gestation and lactation, or at specified times thereafter. Extensive gross observations and microscopic pathology are performed on each animal, and incidences of neoplastic and nonneoplastic lesions are evaluated in age-adjusted statistical comparisons. The collated findings are then interpreted, evaluated, and presented for scientific peer review in public meetings, the aim being to identify qualitatively those environmental and occupational exposures that may likely induce cancer in humans. RP HUFF, JE (reprint author), NIEHS,BOX 12233,RES TRIANGLE PK,NC 27709, USA. NR 40 TC 19 Z9 19 U1 0 U2 0 PU SCAND J WORK ENV HEALTH PI HELSINKI PA TOPELIUKSENKATU 41A, SF-00250 HELSINKI, FINLAND SN 0355-3140 J9 SCAND J WORK ENV HEA JI Scand. J. Work Environ. Health PY 1992 VL 18 SU 1 BP 31 EP 37 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA HZ455 UT WOS:A1992HZ45500005 PM 1411375 ER PT J AU HUFF, J AF HUFF, J TI A HISTORICAL-PERSPECTIVE ON THE CLASSIFICATION DEVELOPED AND USED FOR CHEMICAL CARCINOGENS BY THE NATIONAL TOXICOLOGY PROGRAM DURING 1983-1992 SO SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH LA English DT Article DE CATEGORIES OF CHEMICAL CARCINOGENS; EVALUATING RESULTS FROM LONG-TERM CHEMICAL CARCINOGENICITY EXPERIMENTS; KEY FACTORS IN DATA INTERPRETATION; LEVELS OF EVIDENCE; PUBLIC HEALTH; WEIGHT OF THE EVIDENCE AB To evaluate, interpret, and better communicate the data and findings from long-term chemical carcinogenesis studies on laboratory animals, the National Toxicology Program began using five categories or levels of evidence of carcinogenicity in 1983 (clear, some, equivocal, and no evidence and inadequate experiment). Through July 1991 these defined terms had been used to describe 144 chemical carcinogenesis studies comprising 530 sex-species experiments. Together with a selected descriptor of the chemically associated level of evidence for each experimental unit (male rats, female rats, male mice, female mice), mention is made of the length of the experiment, route of exposure, and the particular tumor type or types for each organ or system affected. The scientific judgements are comprised of this relevant information to inform the readers and users of these evaluations. In this paper the background rationale for the development and proper use of these categories of evidence of carcinogenicity are detailed, together with some personal reflections. RP HUFF, J (reprint author), NIEHS,BOX 12233,RES TRIANGLE PK,NC 27709, USA. NR 36 TC 13 Z9 13 U1 0 U2 1 PU SCAND J WORK ENV HEALTH PI HELSINKI PA TOPELIUKSENKATU 41A, SF-00250 HELSINKI, FINLAND SN 0355-3140 J9 SCAND J WORK ENV HEA JI Scand. J. Work Environ. Health PY 1992 VL 18 SU 1 BP 74 EP 82 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA HZ455 UT WOS:A1992HZ45500011 PM 1411383 ER PT J AU HUFF, J HOEL, D AF HUFF, J HOEL, D TI PERSPECTIVE AND OVERVIEW OF THE CONCEPTS AND VALUE OF HAZARD IDENTIFICATION AS THE INITIAL PHASE OF RISK ASSESSMENT FOR CANCER AND HUMAN HEALTH SO SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH LA English DT Article DE ADVANTAGES AND LIMITATIONS OF HAZARD IDENTIFICATION; ANIMAL TO HUMAN EXTRAPOLATION; CARCINOGENESIS; CHEMICALS; EPIDEMIOLOGIC STUDIES; EXPERIMENTAL STUDIES; IDENTIFYING CHEMICAL CARCINOGENS; LIMITATIONS; LONG-TERM CHEMICAL CARCINOGENICITY EXPERIMENTS; PUBLIC HEALTH ID CARCINOGENICITY AB The identification of potential human health hazards stems from the obvious need to prevent, avoid, reduce, and eliminate exposure to hazardous agents, mixtures of agents, or exposure circumstances. The first step in the risk assessment process centers on determining if a hazard exists. The following strategies are used for this purpose: (i) epidemiologic investigations, (ii) long-term chemical toxicology and carcinogenesis studies on laboratory animals, (ii) shorter-term in vivo and in vitro assays, and (iv) physicochemical structure-activity relationships. Indicator 1 is the most relevant and reliable if adequate data are available; indicator 2 is the most valid and useful alternative for human experience; indicator 3 allows certain toxicologic end points to be identified, but generally needs confirmatory and supportive information; and indicator 4 has made gains in the area of predictivity. The advantages and limitations of each are given. The magnitude of the overall cancer hazard identification effort and a likelihood number of eventual chemical carcinogens have also been estimated. RP HUFF, J (reprint author), NIEHS,BOX 12233,RES TRIANGLE PK,NC 27709, USA. NR 42 TC 20 Z9 20 U1 0 U2 1 PU SCAND J WORK ENV HEALTH PI HELSINKI PA TOPELIUKSENKATU 41A, SF-00250 HELSINKI, FINLAND SN 0355-3140 J9 SCAND J WORK ENV HEA JI Scand. J. Work Environ. Health PY 1992 VL 18 SU 1 BP 83 EP 89 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA HZ455 UT WOS:A1992HZ45500012 PM 1411384 ER PT J AU REGIER, DA KEITH, SJ AF REGIER, DA KEITH, SJ TI SOVIET PROFESSIONAL MENTAL-HEALTH VISIT TO THE UNITED-STATES - AN UPDATE OF ACTIVITIES SO SCHIZOPHRENIA BULLETIN LA English DT Editorial Material AB On September 22, 1990, a Soviet Delegation arrived in Washington, DC, for a 2-week professional visit designed to provide the Delegation with an overview of U.S. mental health research, forensic practice, and service delivery systems. The agenda for the visit included both scientific presentations and site visits to a wide range of mental health and forensic programs in the Washington metropolitan area, as well as smaller group visits to programs in California, Pittsburgh, Chicago, and Wisconsin. RP REGIER, DA (reprint author), NIMH,DIV CLIN RES,PARKLAWN BLDG,RM 10-105,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 1992 VL 18 IS 1 BP 1 EP 2 PG 2 WC Psychiatry SC Psychiatry GA HH615 UT WOS:A1992HH61500001 ER PT J AU WAGMAN, AMI AF WAGMAN, AMI TI REPORT OF A WORKSHOP ON ISSUES IN BRAIN-TISSUE ACQUISITION SO SCHIZOPHRENIA BULLETIN LA English DT Editorial Material AB In the recent past the National Institute of Mental Health (NIMH) has been interested in developing a research initiative to stimulate human brain research on the biological characteristics of schizophrenic brain tissue. The Schizophrenia Research Branch of the Division of Clinical Research of NIMH sponsored a workshop to study the issues of impediments to research on human brain tissue and develop recommendations for solving some of these problems. This article is the first implementation of one of these recommendations, that is, to provide information to the scientific community that brain tissue donations are important and that appropriate means must be taken in order for a donation to proceed. RP WAGMAN, AMI (reprint author), NIMH,SCHIZOPHRENIA RES BRANCH,ROCKVILLE,MD 20857, USA. NR 4 TC 3 Z9 3 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 1992 VL 18 IS 1 BP 149 EP 152 PG 4 WC Psychiatry SC Psychiatry GA HH615 UT WOS:A1992HH61500019 PM 1553493 ER PT J AU TORREY, EF AF TORREY, EF TI ARE WE OVERESTIMATING THE GENETIC CONTRIBUTION TO SCHIZOPHRENIA SO SCHIZOPHRENIA BULLETIN LA English DT Article ID MONOZYGOTIC TWINS DISCORDANT; MULTIPLE-SCLEROSIS; PARKINSONS-DISEASE; NATIONWIDE SERIES; PAIRS; CONCORDANCE; AUTISM; DISORDERS; REGISTRY; FAMILY AB That genetic factors contribute to the etiology of schizophrenia is no longer debated; the nature and magnitude of that contribution, however, are still open for discussion. In this article, concordance rates for twin studies of schizophrenia are reviewed as one means of assessing the magnitude of the genetic contribution. Using only those studies in which representative samples were used and zygosity was determined with reasonable certainty, the pairwise concordance rate for schizophrenia was found to be 28 percent for monozygotic (MZ) and 6 percent for dizygotic (DZ) twins. Review of twin studies of other central nervous system diseases reveals that schizophrenia is most similar to multiple sclerosis (MZ concordance rate 27%). Although genetics remains as the single most clearly defined etiological factor in schizophrenia, the question remains whether we are overestimating the magnitude of the genetic contribution. RP TORREY, EF (reprint author), ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,TWIN STUDY UNIT,2700 MARTIN LUTHER KING AVE SE,WASHINGTON,DC 20032, USA. NR 69 TC 64 Z9 66 U1 0 U2 3 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 1992 VL 18 IS 2 BP 159 EP 170 PG 12 WC Psychiatry SC Psychiatry GA HX285 UT WOS:A1992HX28500001 PM 1621064 ER PT J AU KIRCH, DG LIEBERMAN, JA MATTHEWS, SM AF KIRCH, DG LIEBERMAN, JA MATTHEWS, SM TI 1ST-EPISODE PSYCHOSIS .1. EDITORS INTRODUCTION SO SCHIZOPHRENIA BULLETIN LA English DT Article AB Until recently, there has been a conspicuous lack of studies regarding the earliest phases of psychotic illness, with most research on schizophrenia and related disorders focusing on chronically ill patients. Currently, however, a number of investigators have turned their attention toward this topic, exploring the conceptual issues involved in defining the onset of psychosis, using case registers and population-based samples to do crucial epidemiologic studies on the course of schizophrenia, and developing mechanisms for identifying patients with first-episode psychosis and entering them into active research protocols. This issue of the Schizophrenia Bulletin is devoted to articles representing this full range of conceptual and empirical work on first-episode psychosis. The ultimate goal is for researchers working in this area to develop a network to enhance the sharing of concepts and data, with the eventual possibility of developing combined data bases and collaborative studies. C1 HILLSIDE HOSP,LONG ISL JEWISH MED CTR,GLEN OAKS,NY. RP KIRCH, DG (reprint author), NIMH,DIV CLIN RES,PARKLAWN BLDG,RM 10-105,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 1992 VL 18 IS 2 BP 177 EP 178 PG 2 WC Psychiatry SC Psychiatry GA HX285 UT WOS:A1992HX28500003 PM 1621066 ER PT J AU KIRCH, DG KEITH, SJ MATTHEWS, SM AF KIRCH, DG KEITH, SJ MATTHEWS, SM TI RESEARCH ON 1ST-EPISODE PSYCHOSIS - REPORT ON A NATIONAL-INSTITUTE-OF-MENTAL-HEALTH WORKSHOP SO SCHIZOPHRENIA BULLETIN LA English DT Article ID GENDER DIFFERENCES; SCHIZOPHRENIA AB The need to focus increased research on patients experiencing their first episode of psychosis was emphasized in A National Plan for Schizophrenia Research. To develop strategies for enhancing research in this area, a National Institute of Mental Health Workshop on First-Episode Psychosis was held in 1991. The topics discussed at that workshop are summarized, with key issues including the following: (1) the need for better operational definitions of onset, end of an episode, and relapse of psychosis; (2) careful consideration of inclusion and exclusion criteria related to age, gender, prior treatment, comorbid substance abuse, and similar issues; (3) the challenge of finding patients never exposed to neuroleptics and the value of entering first-episode patients into standardized treatment protocols; (4) the design of followup studies; (5) strategies to increase the pool of applicants; and (6) approaches for increasing power through data sharing and collaboration between groups. RP KIRCH, DG (reprint author), NIMH,DIV CLIN RES,SCHIZOPHRENIA RES BRANCH,PARKLAWN BLDG,RM 10-105,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 20 TC 29 Z9 29 U1 1 U2 1 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 1992 VL 18 IS 2 BP 179 EP 184 PG 6 WC Psychiatry SC Psychiatry GA HX285 UT WOS:A1992HX28500004 ER PT J AU LIEBERMAN, JA MATTHEWS, SM KIRCH, DG AF LIEBERMAN, JA MATTHEWS, SM KIRCH, DG TI 1ST-EPISODE PSYCHOSIS .2. EDITORS INTRODUCTION SO SCHIZOPHRENIA BULLETIN LA English DT Article ID SCHIZOPHRENIA; DEPRESSION; SUICIDE AB The study of first-episode psychosis continues to gain momentum in the research community as evidenced by the range and diversity of topics addressed in both this issue and the previous issue of the Schizophrenia Bulletin (Vol. 18, No. 2). The examination of first-episode patients should provide further insight into the nature of schizophrenia and other illnesses in patients at the same stage of illness and before substantial neuroleptic exposure. These studies will also provide an opportunity to examine unique aspects or complications of the illness. The editors are deeply indebted to the researchers engaging in this extremely important area. We hope that the scientific progress, evident in these issues, will provide the basis by which to better understand the nature of mental illness and provide relief for patients and their families experiencing schizophrenia and related disorders. C1 NIMH,DIV CLIN RES,ROCKVILLE,MD 20857. RP LIEBERMAN, JA (reprint author), ALBERT EINSTEIN COLL MED,LONG ISL JEWISH MED CTR,HILLSIDE HOSP,75-59 263RD ST,GLEN OAKS,NY 11004, USA. NR 7 TC 8 Z9 8 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 1992 VL 18 IS 3 BP 349 EP 350 PG 2 WC Psychiatry SC Psychiatry GA JL328 UT WOS:A1992JL32800002 ER PT J AU LALLEY, TL HOHMANN, AA WINDLE, CD NORQUIST, GS KEITH, SJ BURKE, JD AF LALLEY, TL HOHMANN, AA WINDLE, CD NORQUIST, GS KEITH, SJ BURKE, JD TI CARING FOR PEOPLE WITH SEVERE MENTAL-DISORDERS - A NATIONAL PLAN TO IMPROVE SERVICES - EDITORS INTRODUCTION SO SCHIZOPHRENIA BULLETIN LA English DT Editorial Material C1 TEXAS A&M UNIV SYST,HLTH SCI CTR,DEPT PSYCHIAT & BEHAV SCI,TEMPLE,TX 76508. RP LALLEY, TL (reprint author), NIMH,DIV APPL & SERV RES,SERV RES BRANCH,OFF RURAL MENTAL HLTH SERV,ROCKVILLE,MD 20857, USA. RI Burke, Jack/I-4440-2012 OI Burke, Jack/0000-0001-5868-1695 NR 4 TC 1 Z9 1 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 1992 VL 18 IS 4 BP 559 EP 560 PG 2 WC Psychiatry SC Psychiatry GA JT834 UT WOS:A1992JT83400002 ER PT J AU STEINWACHS, DM CULLUM, HM DORWART, RA FLYNN, L FRANK, R FRIEDMAN, MB HERZ, MI MULVEY, EP SNOWDEN, L TEST, MA TREMAINE, LS WINDLE, CD AF STEINWACHS, DM CULLUM, HM DORWART, RA FLYNN, L FRANK, R FRIEDMAN, MB HERZ, MI MULVEY, EP SNOWDEN, L TEST, MA TREMAINE, LS WINDLE, CD TI SERVICE SYSTEMS RESEARCH SO SCHIZOPHRENIA BULLETIN LA English DT Article ID COMMUNITY MENTAL-HEALTH; STAFFING PATTERNS; PSYCHIATRIC-PATIENTS; FOUNDATION PROGRAM; JOB-SATISFACTION; SOCIAL-WORKERS; UNITED-STATES; CARE; ILL; SCHIZOPHRENIA C1 UNIV WISCONSIN,MADISON,WI 53706. NIMH,ROCKVILLE,MD 20857. NR 142 TC 23 Z9 22 U1 8 U2 14 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 1992 VL 18 IS 4 BP 627 EP 668 PG 42 WC Psychiatry SC Psychiatry GA JT834 UT WOS:A1992JT83400004 PM 1439614 ER PT J AU MECHANIC, D BEVILACQUA, JJ GOLDMAN, H HARGREAVES, W HOWE, J KNISLEY, M SCHERL, DJ STUART, G UNHJEM, MB LALLEY, TL AF MECHANIC, D BEVILACQUA, JJ GOLDMAN, H HARGREAVES, W HOWE, J KNISLEY, M SCHERL, DJ STUART, G UNHJEM, MB LALLEY, TL TI RESEARCH RESOURCES SO SCHIZOPHRENIA BULLETIN LA English DT Article ID TREATMENT PROGRAM; SCIENCE C1 NIMH,DIV APPL & SERV RES,SERV RES BRANCH,ROCKVILLE,MD 20857. NR 15 TC 4 Z9 4 U1 2 U2 2 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 1992 VL 18 IS 4 BP 669 EP 700 PG 32 WC Psychiatry SC Psychiatry GA JT834 UT WOS:A1992JT83400005 PM 1439615 ER PT J AU TORREY, EF AF TORREY, EF TI WHAT CAN MONOZYGOTIC TWINS TELL US ABOUT SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,TWIN STUDY UNIT,WASHINGTON,DC 20032. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 1992 VL 6 IS 2 BP 94 EP 95 DI 10.1016/0920-9964(92)90096-N PG 2 WC Psychiatry SC Psychiatry GA HB658 UT WOS:A1992HB65800015 ER PT J AU TORREY, EF BOWLER, AE RAWLINGS, R AF TORREY, EF BOWLER, AE RAWLINGS, R TI SCHIZOPHRENIA AND THE 1957 INFLUENZA EPIDEMIC SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,CTR NEUROSCI,WASHINGTON,DC 20032. NIAAA,ROCKVILLE,MD 20852. NR 0 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 1992 VL 6 IS 2 BP 100 EP 100 DI 10.1016/0920-9964(92)90107-G PG 1 WC Psychiatry SC Psychiatry GA HB658 UT WOS:A1992HB65800026 ER PT J AU MCNEIL, T TORREY, F SJOSTROM, K CANTORGRAAE, E BOWLER, A TAYLOR, E HIGGINS, N AF MCNEIL, T TORREY, F SJOSTROM, K CANTORGRAAE, E BOWLER, A TAYLOR, E HIGGINS, N TI HISTORIES OF OBSTETRIC COMPLICATIONS AND NEONATAL ABNORMALITIES IN MONOZYGOTIC TWINS CONCORDANT AND DISCORDANT FOR SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 UNIV LUND,ALLAMANNA SJUKHUSET,DEPT PSYCHIAT,S-21401 MALMO,SWEDEN. ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,TWIN STUDY UNIT,WASHINGTON,DC 20032. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 1992 VL 6 IS 2 BP 106 EP 106 DI 10.1016/0920-9964(92)90124-N PG 1 WC Psychiatry SC Psychiatry GA HB658 UT WOS:A1992HB65800043 ER PT J AU BRUTON, CJ STEVENS, JR FRITH, CD AF BRUTON, CJ STEVENS, JR FRITH, CD TI PSYCHOSIS AND EPILEPSY - CLINICOPATHOLOGICAL CORRELATIONS SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 CLIN RES CTR,DIV PSYCHIAT,HARROW,ENGLAND. NIMH,ST ELIZABETHS HOSP,WASHINGTON,DC 20032. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 1992 VL 6 IS 2 BP 154 EP 154 DI 10.1016/0920-9964(92)90234-V PG 1 WC Psychiatry SC Psychiatry GA HB658 UT WOS:A1992HB65800153 ER PT J AU STEVENS, JR CASANOVA, M HSIEH, W POLTORAK, M FREED, W AF STEVENS, JR CASANOVA, M HSIEH, W POLTORAK, M FREED, W TI AXON COUNT IN NUCLEUS-ACCUMBENS IN SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 NIMH,NEUROSCI RES CTR,WASHINGTON,DC 20032. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JAN PY 1992 VL 6 IS 2 BP 154 EP 154 DI 10.1016/0920-9964(92)90233-U PG 1 WC Psychiatry SC Psychiatry GA HB658 UT WOS:A1992HB65800152 ER PT B AU FAUCI, AS AF FAUCI, AS BE ROSSI, GB DIANZANI, F BETHGIRALDO, E GIRALDO, G CHIECOBIANCHI, L VERANI, P TI IMPACT OF BIOMEDICAL-RESEARCH ON THE AIDS EPIDEMIC SO SCIENCE CHALLENGING AIDS LA English DT Proceedings Paper CT 7TH INTERNATIONAL CONF ON AIDS CY JUN 16-21, 1991 CL FLORENCE, ITALY SP EUROPEAN ECON COMMUNITY, REG TOSCANA, ASSOC NAZL LOTTA CONTRO AIDS, ASSOC SALUTE DONNA, IST SUPER SANITA, ITALIAN MINIST HLTH, WHO, INT AIDS SOC, COMMUNE FIRENZE, FDN ITALIANA RIC CANC RP FAUCI, AS (reprint author), NIAID,BETHESDA,MD 20892, USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU KARGER PI BASEL PA BASEL BN 3-8055-5485-0 PY 1992 BP 1 EP 14 PG 14 WC Immunology; Medicine, Research & Experimental; Pathology; Virology SC Immunology; Research & Experimental Medicine; Pathology; Virology GA BU75U UT WOS:A1992BU75U00003 ER PT B AU BRODER, S AF BRODER, S BE ROSSI, GB DIANZANI, F BETHGIRALDO, E GIRALDO, G CHIECOBIANCHI, L VERANI, P TI AIDS - PROGRESS AND CHALLENGES IN THERAPY SO SCIENCE CHALLENGING AIDS LA English DT Proceedings Paper CT 7TH INTERNATIONAL CONF ON AIDS CY JUN 16-21, 1991 CL FLORENCE, ITALY SP EUROPEAN ECON COMMUNITY, REG TOSCANA, ASSOC NAZL LOTTA CONTRO AIDS, ASSOC SALUTE DONNA, IST SUPER SANITA, ITALIAN MINIST HLTH, WHO, INT AIDS SOC, COMMUNE FIRENZE, FDN ITALIANA RIC CANC RP BRODER, S (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA BASEL BN 3-8055-5485-0 PY 1992 BP 15 EP 23 PG 9 WC Immunology; Medicine, Research & Experimental; Pathology; Virology SC Immunology; Research & Experimental Medicine; Pathology; Virology GA BU75U UT WOS:A1992BU75U00004 ER PT B AU GALLO, RC AF GALLO, RC BE ROSSI, GB DIANZANI, F BETHGIRALDO, E GIRALDO, G CHIECOBIANCHI, L VERANI, P TI AIDS AND RELATED MALIGNANCIES SO SCIENCE CHALLENGING AIDS LA English DT Proceedings Paper CT 7TH INTERNATIONAL CONF ON AIDS CY JUN 16-21, 1991 CL FLORENCE, ITALY SP EUROPEAN ECON COMMUNITY, REG TOSCANA, ASSOC NAZL LOTTA CONTRO AIDS, ASSOC SALUTE DONNA, IST SUPER SANITA, ITALIAN MINIST HLTH, WHO, INT AIDS SOC, COMMUNE FIRENZE, FDN ITALIANA RIC CANC RP GALLO, RC (reprint author), NCI,TUMOR CELL BIOL LAB,BLDG 37,ROOM 6A-09,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU KARGER PI BASEL PA BASEL BN 3-8055-5485-0 PY 1992 BP 116 EP 125 PG 10 WC Immunology; Medicine, Research & Experimental; Pathology; Virology SC Immunology; Research & Experimental Medicine; Pathology; Virology GA BU75U UT WOS:A1992BU75U00010 ER PT B AU PLUDA, JM LIETZAU, J TOSATO, G VENZON, D BIRX, DL BRODER, S YARCHOAN, R AF PLUDA, JM LIETZAU, J TOSATO, G VENZON, D BIRX, DL BRODER, S YARCHOAN, R BE ROSSI, GB DIANZANI, F BETHGIRALDO, E GIRALDO, G CHIECOBIANCHI, L VERANI, P TI DEVELOPMENT OF OPPORTUNISTIC NON-HODGKINS-LYMPHOMAS IN SEVERELY IMMUNOSUPPRESSED HIV-INFECTED PATIENTS RECEIVING LONG-TERM ANTIRETROVIRAL THERAPY SO SCIENCE CHALLENGING AIDS LA English DT Proceedings Paper CT 7TH INTERNATIONAL CONF ON AIDS CY JUN 16-21, 1991 CL FLORENCE, ITALY SP EUROPEAN ECON COMMUNITY, REG TOSCANA, ASSOC NAZL LOTTA CONTRO AIDS, ASSOC SALUTE DONNA, IST SUPER SANITA, ITALIAN MINIST HLTH, WHO, INT AIDS SOC, COMMUNE FIRENZE, FDN ITALIANA RIC CANC RP PLUDA, JM (reprint author), NCI,9000 ROCKVILLE PIKE,BLDG 10,RM 13N248,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA BASEL BN 3-8055-5485-0 PY 1992 BP 196 EP 206 PG 11 WC Immunology; Medicine, Research & Experimental; Pathology; Virology SC Immunology; Research & Experimental Medicine; Pathology; Virology GA BU75U UT WOS:A1992BU75U00016 ER PT J AU SMITH, PT COBB, BG AF SMITH, PT COBB, BG TI PHYSIOLOGICAL AND ENZYMATIC CHARACTERISTICS OF PRIMED, RE-DRIED, AND GERMINATED PEPPER SEEDS (CAPSICUM-ANNUUM-L) SO SEED SCIENCE AND TECHNOLOGY LA English DT Article AB Capsicum annuwn L. seeds were primed in NaCl solutions to determine (i) if soluble protein levels and enzymatic activities increased during priming were retained by the seeds after priming and (ii) what influence priming has on the respiratory rates of seeds during subsequent germination. Pepper seeds were primed in -0.90 and -1.35 MPa (200 and 300 mM, respectively) NaCl solutions, then re-dried (PR) or re-dried and germinated (PRG) in DDH20 (double distilled water). PR and PRG seeds retained the higher soluble protein levels, aldolase activity, and isocitrate lyase (ICL) activity when compared to appropiate controls: dry, unprimed and dry, unprimed seeds germinated in DDH20, respectively. In PR seeds, glucose-6-phosphate dehydrogenase (G6P) activity was 50% higher than in dry, unprimed seeds (controls), while 6-phosphogluconate dehydrogenase (6PG) activity was not affected, and alcohol dehydrogenase (ADH) activity decreased by 44%. G6P and 6PG activities of PRG seeds were the same as dry, unprimed seeds germinated in DDH2O (controls), while ADH activity decreased below the levels of detection. Seeds primed for 12 days or longer in the -0.90 MPa solution, re-dried, and germinated in DDH2O had significantly (P less-than-or-equal-to 0.01) higher respiratory rates then dry, unprimed seeds when monitored over a four day period. Ninety percent of the seeds in the -0.90 MPa solution germinated after 12 days of priming. These primed seeds retained the elevated respiration lcvels which accompanied radicle emergence after drying and re-hydration. However, drying primed seeds with exposed radiclcs prevented furthcr development when the seeds were reimbibed with DDH2O. The respiratory rates of PRG seeds primed in -1.35 MPa solutions were the same as unprimed seeds germinated in DDH2O (controls). RP SMITH, PT (reprint author), NIAID,LI BLDG 10,RM 11N 258,BETHESDA,MD 20892, USA. NR 0 TC 18 Z9 22 U1 0 U2 4 PU ISTA PI ZURICH PA RECKENHOLZ PO BOX 412, CH-8046 ZURICH, SWITZERLAND SN 0251-0952 J9 SEED SCI TECHNOL JI Seed Sci. Technol. PY 1992 VL 20 IS 3 BP 503 EP 513 PG 11 WC Agronomy; Plant Sciences; Horticulture SC Agriculture; Plant Sciences GA KV388 UT WOS:A1992KV38800018 ER PT B AU WURTZ, RH DUFFY, CJ AF WURTZ, RH DUFFY, CJ BE COHEN, B TOMKO, DL GUEDRY, F TI NEURONAL CORRELATES OF OPTIC FLOW STIMULATION SO SENSING AND CONTROLLING MOTION: VESTIBULAR AND SENSORIMOTOR FUNCTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Proceedings Paper CT CONF ON SENSING AND CONTROLLING MOTION : VESTIBULAR AND SENSORIMOTOR FUNCTION CY JUL 07-11, 1991 CL PALO ALTO, CA SP NEW YORK ACAD SCI, NASA, NIDOCD, USN, OFF NAVAL RES RP WURTZ, RH (reprint author), NEI,SENSORIMOTOR RES LAB,BLDG 10,ROOM 10C101,BETHESDA,MD 20892, USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA NEW YORK BN 0-89766-734-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1992 VL 656 BP 205 EP 219 PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA BW41U UT WOS:A1992BW41U00015 ER PT B AU MILES, FA BUSETTINI, C AF MILES, FA BUSETTINI, C BE COHEN, B TOMKO, DL GUEDRY, F TI OCULAR COMPENSATION FOR SELF-MOTION - VISUAL MECHANISMS SO SENSING AND CONTROLLING MOTION: VESTIBULAR AND SENSORIMOTOR FUNCTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Proceedings Paper CT CONF ON SENSING AND CONTROLLING MOTION : VESTIBULAR AND SENSORIMOTOR FUNCTION CY JUL 07-11, 1991 CL PALO ALTO, CA SP NEW YORK ACAD SCI, NASA, NIDOCD, USN, OFF NAVAL RES RP MILES, FA (reprint author), NEI,SENSORIMOTOR RES LAB,BLDG 10,ROOM 10C101,BETHESDA,MD 20892, USA. NR 0 TC 34 Z9 34 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA NEW YORK BN 0-89766-734-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1992 VL 656 BP 220 EP 232 DI 10.1111/j.1749-6632.1992.tb25211.x PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA BW41U UT WOS:A1992BW41U00016 PM 1599145 ER PT J AU MOSS, N STONE, MC SMITH, JB AF MOSS, N STONE, MC SMITH, JB TI CHILD HEALTH OUTCOMES AMONG CENTRAL-AMERICAN REFUGEES AND IMMIGRANTS IN BELIZE SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE MIGRATION; REFUGEE; WEIGHT-FOR-AGE; DIARRHEA; RESPIRATORY ILLNESS ID MEDICAL MISSION; EL-SALVADOR; GROWTH AB The purpose of this study was to investigate the effect of international migration, including refugee status, upon child health outcomes. Data were drawn from a survey conducted in 1989 in three settlements in Belize, Central America, that have a high proportion of refugees and economic immigrants living side-by-side with the local population. In two of the settlements, the entire population of mothers with children under 6 was interviewed; in the third settlement a two-thirds random sample was interviewed. Health history data were obtained for 255 children of 134 mothers, from whom sociodemographic data were also collected. The majority of children were born to Salvadoran or Guatemalan mothers, but native and naturalized Belizeans in the survey communities were included for comparison purposes. Migration, the exposure variable, was characterized by mother's residency/refugee legal status, nationality, and duration of time in country. Socioeconomic and proximate control variables were included as suggested by the Mosley-Chen framework. Despite normal birthweight averaging 3374 g, a large proportion of children are at the lowest percentiles of the weight-for-age curves (44% below the tenth percentile for the international reference population). A high incidence of diarrheal and respiratory illnesses (30% and 47% of children, respectively, having frequent episodes), and 50% of children with measles vaccination appropriate for age, indicate a population with high potential morbidity. Logistic regression was used to model the effects of migration on weight-for-age and frequency of diarrheal and respiratory tract episodes independent of socioeconomic and proximate factors, as suggested by the Mosley-Chen framework. Once these socioeconomic and proximate variables were controlled for, migration contributed little to the models. It appears that the poverty of migrants-irrespective of legal status, origin, or length of time in country-may override migration. Also, study findings suggest that the children of refugees and immigrants have intense health needs even in a relatively benign social environment, as do the children of native Belizeans. The study affirmed the utility of the Mosley-Chen framework, and further tests in other migration contexts are suggested. Current efforts of government and non-governmental programs to direct public health measures towards whole settlements rather than to groups defined by legal status should be supported. Policies that decrease socioeconomic marginalization by integrating refugees and immigrants into the local labor force, educational facilities, and health services may contribute to improved child health. C1 UNIV TEXAS,DEPT ANTHROPOL,AUSTIN,TX 78712. UNIV N CAROLINA,DEPT HLTH BEHAV HLTH EDUC,CHAPEL HILL,NC 27514. RP MOSS, N (reprint author), NICHHD,CTR POPULAT RES,DEMOG & BEHAV SCI BRANCH,BETHESDA,MD 20892, USA. NR 28 TC 5 Z9 5 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD JAN PY 1992 VL 34 IS 2 BP 161 EP 167 DI 10.1016/0277-9536(92)90093-6 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA GY697 UT WOS:A1992GY69700009 PM 1738869 ER PT B AU MCCRAY, AT AF MCCRAY, AT GP DEF ADV RES PROJECTS AGCY TI INFERENCING IN INFORMATION-RETRIEVAL SO SPEECH AND NATURAL LANGUAGE LA English DT Proceedings Paper CT DARPA Speech and Natural Language Workshop CY FEB 23-26, 1992 CL HARRIMAN, NY SP DEF ADV RES PROJECTS AGCY, SOFTWARE & INTELLIGENT SYST TECHNOL OFF C1 NATL LIB MED,BETHESDA,MD 20894. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MORGAN KAUFMANN PUB INC PI SAN MATEO PA 2929 CAMPUS DRIVE, SAN MATEO, CA 94403 BN 1-55860-272-0 PY 1992 BP 218 EP 223 PG 6 WC Computer Science, Artificial Intelligence; Computer Science, Software Engineering SC Computer Science GA BA93C UT WOS:A1992BA93C00035 ER PT J AU FREEDMAN, LS PEE, D MIDTHUNE, DN AF FREEDMAN, LS PEE, D MIDTHUNE, DN TI THE PROBLEM OF UNDERESTIMATING THE RESIDUAL ERROR VARIANCE IN FORWARD STEPWISE REGRESSION SO STATISTICIAN LA English DT Article ID VARIABLE SELECTION; EQUATIONS AB Under the global null hypothesis that all covariates are unrelated to the outcome variables, forward stepwise regression procedures should have the property that the probability of selecting a given variable and finding it significant at the alpha level is equal to alpha. Because of the problem of underestimating the residual error variance the actual probability can be very different from alpha. This problem becomes of practical concern when the ratio of the number of variables to the number of observations becomes greater than 0.25, and is more serious for logistic than for linear regression. C1 NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,BETHESDA,MD 20892. INFORMAT MANAGEMENT SERV INC,ROCKVILLE,MD 20852. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD 20904. NR 15 TC 15 Z9 15 U1 0 U2 4 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD, OXON, ENGLAND OX4 1JF SN 0039-0526 J9 STATISTICIAN JI Statistician PY 1992 VL 41 IS 4 BP 405 EP 412 DI 10.2307/2349005 PG 8 WC Statistics & Probability SC Mathematics GA JT484 UT WOS:A1992JT48400003 ER PT J AU SALERNO, JA MURPHY, DG HORWITZ, B DECARLI, CS SCHAPIRO, MB RAPOPORT, SI AF SALERNO, JA MURPHY, DG HORWITZ, B DECARLI, CS SCHAPIRO, MB RAPOPORT, SI TI BRAIN STRUCTURAL-CHANGES IN HYPERTENSIVE SUBJECTS - QUANTITATION WITH MAGNETIC-RESONANCE-IMAGING SO STROKE LA English DT Meeting Abstract C1 NIA,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 1992 VL 23 IS 1 BP 143 EP 143 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA HA876 UT WOS:A1992HA87600058 ER PT B AU BLAIR, A AF BLAIR, A BE Myers, ML Herrick, RF Olenchock, SA Myers, JR Parker, JE Hard, DL Wilson, K TI AN OVERVIEW OF POTENTIAL HEALTH HAZARDS AMONG FARMERS FROM USE OF PESTICIDES SO SURGEON GENERAL'S CONFERENCE ON AGRICULTURAL SAFETY AND HEALTH LA English DT Proceedings Paper CT Surgeon Generals Conference on Agricultural Safety and Health CY APR 30-MAY 03, 1991 CL DES MOINES, IA SP US DHHS, PUBLIC HLTH SERV, CTR DIS CONTROL, NATL INST OCCUPAT SAFETY & HLTH C1 NCI,OCCUPAT STUDIES SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU US DEPT COMMERCE NATL TECH INFORMATION SERVICE PI WASHINGTON PA 14TH & CONSTITUTION AVE, WASHINGTON, DC 20230 PY 1992 BP 229 EP 242 PG 14 WC Agronomy; Public, Environmental & Occupational Health; Public Administration SC Agriculture; Public, Environmental & Occupational Health; Public Administration GA BC46H UT WOS:A1992BC46H00033 ER PT B AU Hoagwood, K AF Hoagwood, K GP RTCCMH RTCCMH TI Bridging methodological paradigms: Conducting service system research on children, adolescents and their families SO SYSTEM OF CARE FOR CHILDREN'S MENTAL HEALTH: EXPANDING THE RESEARCH BASE, ANNUAL RESEARCH CONFERENCE PROCEEDINGS LA English DT Proceedings Paper CT 5th Annual Research Conference on a System of Care for Childrens Mental Health - Expanding the Research Base CY MAR 02-04, 1992 CL TAMPA, FL AB Services research for children, adolescents and their families increasingly involves both multidisciplinary investigations and multiple service systems. Different disciplinary paraded underlie the research perspectives by which designs and methodologies are constructed. Further, exigencies within service sectors often challenge conventional methodological principles. This symposium was convened of researchers whose investigations of children's mental health services have been conducted within varying service sectors, including education, juvenile justice, child welfare, and general health. Me symposium offered an opportunity to compare, and think about the different research paradigms, projects, and methodological constraints involved in services research across service systems. C1 NIMH, Rockville, MD 20857 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU RESEARCH & TRAINING CENTER CHILDRENS MENTAL HEALTH PI TAMPA PA LOUIS PARTE FL MENTAL HEATLH INST, 13301 BRUCE B DOWNS BLVD, TAMPA, FL 33612-3899 USA PY 1992 BP 69 EP 71 PG 3 WC Psychology, Clinical SC Psychology GA BU21V UT WOS:000175367600009 ER PT B AU STEINBERG, AD MUIR, J SCOTT, DE GOURLEY, MF AF STEINBERG, AD MUIR, J SCOTT, DE GOURLEY, MF BE SESSA, A MERONI, M BATTINI, G TI APPROACH TO LUPUS NEPHRITIS BASED UPON RANDOMIZED TRIALS SO SYSTEMIC LUPUS ERYTHEMATOSUS : RENAL VASCULITIS SE CONTRIBUTIONS TO NEPHROLOGY LA English DT Proceedings Paper CT 2ND SEMINAR ON RENAL INVOLVEMENT IN SYSTEMIC VASCULITIS CY SEP 21, 1991 CL VIMERCATE, ITALY RP STEINBERG, AD (reprint author), NIAMSD,ARTHRIT & RHEUMATISM BRANCH,BLDG 10,ROOM 9N-218,BETHESDA,MD 20892, USA. NR 0 TC 9 Z9 10 U1 0 U2 0 PU KARGER PI BASEL PA BASEL BN 3-8055-5603-9 J9 CONTRIB NEPHROL JI Contrib.Nephrol. PY 1992 VL 99 BP 46 EP 54 PG 9 WC Pathology; Urology & Nephrology SC Pathology; Urology & Nephrology GA BX06Y UT WOS:A1992BX06Y00006 PM 1458925 ER PT J AU ABUSHAKRA, A AF ABUSHAKRA, A TI THE MODULATORY EFFECTS OF TRYPTAMINE AND TYRAMINE ON THE S9-MEDIATED MUTAGENESIS OF IQ AND MEIQ IN SALMONELLA STRAIN TA98 SO TERATOGENESIS CARCINOGENESIS AND MUTAGENESIS LA English DT Article DE FOOD MUTAGENS; BIOGENIC AMINES; MODULATORS; COMUTAGENS; ANTIMUTAGENS; AROMATIC AMINES; METABOLIC ACTIVATION ID METABOLIC-ACTIVATION; HETEROCYCLIC AMINES; BROILED SARDINE; AROMATIC-AMINES; BEEF EXTRACT; F344 RATS; INDUCTION; 2-AMINO-3-METHYLIMIDAZO<4,5-F>QUINOLINE; PYROLYSATE; 2-AMINO-3,4-DIMETHYLIMIDAZO<4,5-F>QUINOLINE AB The S9-mediated mutagenesis of IQ and MeIQ in Salmonella strain TA98 was modulated by introduction to the assay of tryptamine or tyramine. Both biogenic amines inhibited or enhanced the mutagenic response as a function of amine concentration, strain of rat used as the S9 source, and the IQ-type mutagen tested. Enhancement of IQ mutagenesis by tryptamine (10-80 muM) was observed in the presence of S9 preparations derived from Aroclor 1254-pretreated Fischer rats; the enhancing effect ceased at tryptamine concentrations > 160 muM. When Sprague-Dawley-S9 or Wistar-S9 were used for activation, the enhancement of IQ mutagenesis by tryptamine shifted to inhibition at tryptamine concentrations >40 muM, with Sprague-Dawley-S9, and > 20 muM, with Wistar-S9. By contrast, MeIQ-mutagenesis was enhanced by tryptamine (10 - 160 muM), regardless of the rat strain used as S9 source. Tyramine was a weaker enhancer of MeIQ mutagenesis than was tryptamine and, unlike tryptamine, its inhibitory effects on IQ mutagenesis were observed only with Wistar-S9. Tryptamine (10-80 muM) inhibited cytochromes P450IA1 and P450IA2 activities, monitored by the O-deethylation of ethoxyresorufin and Glu-P-1 mutagenesis in TA98, respectively. These data suggest that the effects of biogenic amines on IQ and MeIQ bioactivation are complex. Furthermore, this study demonstrates that tryptamine and tyramine act both as enhancers (comutagens) and as inhibitors (antimutagens) of IQ and MeIQ mutagenesis, depending on the testing conditions. C1 NIEHS,EXPTL CARCINOGENESIS & MUTAGENESIS BRANCH,RES TRIANGLE PK,NC 27709. NR 34 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0270-3211 J9 TERATOGEN CARCIN MUT JI Teratogenesis Carcinog. Mutagen. PY 1992 VL 12 IS 4 BP 187 EP 196 DI 10.1002/tcm.1770120405 PG 10 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA KF105 UT WOS:A1992KF10500004 PM 1363160 ER PT J AU ABBOTT, BD HARRIS, MW BIRNBAUM, LS AF ABBOTT, BD HARRIS, MW BIRNBAUM, LS TI COMPARISONS OF THE EFFECTS OF TCDD AND HYDROCORTISONE ON GROWTH-FACTOR EXPRESSION PROVIDE INSIGHT INTO THEIR INTERACTION IN THE EMBRYONIC MOUSE PALATE SO TERATOLOGY LA English DT Article ID INDUCED CLEFT-PALATE; TGF-BETA; EGF RECEPTOR; FACTOR-ALPHA; DIFFERENTIAL EXPRESSION; CELL-PROLIFERATION; SECONDARY PALATE; RETINOIC ACID; MAMMALIAN DEVELOPMENT; NUCLEOTIDE-SEQUENCE AB Cleft palate (CP) can be induced in embryonic mice by a wide range of compounds, including glucocorticoids and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Hydrocortisone (HC), a glucocorticoid, retards embryonic growth producing small palatal shelves, while TCDD exposure blocks the fusion of normally sized shelves. TCDD induction of CP involves altered differentiation of the medial epithelial cells. Recent studies indicate that growth factors such as EGF, TGF-alpha, TGF-beta-1, and TGF-beta-2 are involved in palatogenesis, regulating proliferation, differentiation, and extracellular matrix production. A synergism has been observed between HC and TCDD in which doses too low to induce CP alone are able to produce > 90% incidence when coadministered. In the present study a standard teratology protocol was performed in C57BL/6N mice to examine the synergism at doses lower than those previously published. Data from this study indicate synergistic interactions at doses as low as 3-mu-g TCDD/kg + 1 mg HC/kg. This extreme sensitivity suggests the involvement of a receptor-mediated mechanism possibly resulting in altered regulation of gene expression. Mechanisms of interaction were further studied by comparing growth of the shelves, fate of the medial epithelium, and expression of growth factor mRNAs and peptides. Pregnant mice were dosed on GDs 10-13 with HC (100 mg/kg sc) or with HC (25 mg/kg sc) + TCDD (3-mu-g/kg orally), doses producing 30% and 99% CP, respectively. The interaction between HC and TCDD results in a small HC-like palate, rather than the morphology typical of TCDD-induced clefting. Both compounds inhibited programmed cell death of the medial epithelium, which instead differentiated into an oral-like epithelium. The alterations in growth factor expression after HC or HC + TCDD were similar. Expression of EGF, TGF-beta-1, TGF-beta-2, and EGF receptor increased in specific palatal regions. Increased levels of mRNA were observed only for TGF-beta-1. The effects of TCDD alone on growth factor expression differ from those seen with HC or HC + TCDD. These divergent effects on growth factor expression may contribute to the differences in shelf size and thus to the different mechanisms of HC and TCDD clefting. Thus the synergism between HC and TCDD may involve similar and potentially additive effects on regulators of proliferation and differentiation in the palate, but additional contributing factors cannot be excluded. C1 US EPA,DIV ENVIRONM TOXICOL,RES TRIANGLE PK,NC 27711. NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. RP ABBOTT, BD (reprint author), US EPA,HLTH EFFECTS RES LAB,DIV DEV TOXICOL,RES TRIANGLE PK,NC 27711, USA. NR 71 TC 53 Z9 58 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 0040-3709 J9 TERATOLOGY JI Teratology PD JAN PY 1992 VL 45 IS 1 BP 35 EP 53 DI 10.1002/tera.1420450104 PG 19 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA GY761 UT WOS:A1992GY76100003 PM 1731395 ER PT B AU LEONARD, HL SWEDO, SE RAPOPORT, JL RICKLER, KC TOPOL, D LEE, S RETTEW, D AF LEONARD, HL SWEDO, SE RAPOPORT, JL RICKLER, KC TOPOL, D LEE, S RETTEW, D BE CHASE, TN FRIEDHOFF, AJ COHEN, DJ TI TOURETTE SYNDROME AND OBSESSIVE-COMPULSIVE DISORDER SO TOURETTE SYNDROME: GENETICS, NEUROBIOLOGY, AND TREATMENT SE ADVANCES IN NEUROLOGY LA English DT Proceedings Paper CT 2ND INTERNATIONAL SCIENTIFIC SYMP ON TOURETTE SYNDROME CY JUN, 1991 CL BOSTON, MA SP NINDS, NIMH, GATEPOSTS FDN, TOURETTE SYNDROME ASSOC, PERMANENT RES FUND RP LEONARD, HL (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 33 Z9 33 U1 0 U2 0 PU RAVEN PRESS PI NEW YORK PA NEW YORK BN 0-88167-922-4 J9 ADV NEUROL JI Adv.Neurol. PY 1992 VL 58 BP 83 EP 93 PG 11 WC Genetics & Heredity; Clinical Neurology; Neurosciences SC Genetics & Heredity; Neurosciences & Neurology GA BW43N UT WOS:A1992BW43N00010 PM 1414648 ER PT J AU HASEMAN, JK RAO, GN AF HASEMAN, JK RAO, GN TI EFFECTS OF CORN-OIL, TIME-RELATED CHANGES, AND INTER-LABORATORY VARIABILITY ON TUMOR OCCURRENCE IN CONTROL FISCHER-344 (F344/N) RATS SO TOXICOLOGIC PATHOLOGY LA English DT Article DE TUMOR RATES; CORN OIL GAVAGE; F344 RATS; HISTORICAL CONTROL DATA; EXTRA-BINOMIAL VARIABILITY; RODENT CARCINOGENICITY STUDIES AB Survival, body weight, and site-specific tumor rates in untreated, com oil gavage, and water gavage control Fischer 344 (F344/N) rats from 88 National Toxicology Program (NTP) long term carcinogenicity studies were evaluated to determine which factors were primarily responsible for inter-study variability. For male rats, previously-reported decreases in leukemia and increases in body weight, survival, and pancreatic acinar cell tumors attributable to com oil gavage were confirmed. Com oil did not appear to affect tumor rates in female rats. The gavage technique per se did not appear to influence tumor rates in rats of either sex. Previously reported time-related increases in certain site-specific neoplasia in control rats appeared to have stabilized in recent years, but control tumor rates are still much greater than those seen a decade ago. More recent studies continue to show increasing rates of leukemia and mammary gland tumors and decreasing survival. Female rats also continue to show time-related increases in maximum mean body weight. Inter-laboratory variability in body weight and in the rates of a number of site-specific neoplasms were also significant. High mean body weights in control groups were found to be associated with increased rates of mammary and pituitary tumors. Our evaluation supports the view that if historical control data are to be utilized in the interpretation of experimental results, primary emphasis should be given to lab and route of administration-specific tumor rates for studies that are contemporary to the study under evaluation. It also suggests that certain experimental design changes (e.g., dietary modifications) may be needed to reduce tumor rates and to increase survival. RP HASEMAN, JK (reprint author), NIEHS,DIV BIOMETRY & RISK ASSESSMENT,POB 12233,MD B3-02,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 58 Z9 59 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 1992 VL 20 IS 1 BP 52 EP 60 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA JB475 UT WOS:A1992JB47500007 PM 1411131 ER PT J AU KANNO, J ONODERA, H FURUTA, K MAEKAWA, A KASUGA, T HAYASHI, Y AF KANNO, J ONODERA, H FURUTA, K MAEKAWA, A KASUGA, T HAYASHI, Y TI TUMOR-PROMOTING EFFECTS OF BOTH IODINE DEFICIENCY AND IODINE EXCESS IN THE RAT-THYROID SO TOXICOLOGIC PATHOLOGY LA English DT Article DE NEOPLASIA; NEOPLASMS; HYPERPLASIA; THYROID-STIMULATING HORMONE; THYROXINE; PITUITARY-THYROID AXIS; WOLFF-CHAIKOFF EFFECT; ESCAPE PHENOMENON; RECOMMENDED IODINE INTAKE AB Thyroid tumor-promoting effects of iodine deficiency and iodine excess were investigated in a rodent 2-stage model to estimate an optimal iodine intake range that would not effectively promote development of thyroid neoplasia. Six-week-old male F344 rats were given a single subcutaneous injection of 2,800 mg/kg body weight N-bis(2-hydroxypropyl)-nitrosamine (DHPN) or saline vehicle, maintained on Remington's iodine-deficient diet (21 +/- 2 ng/g iodide), and supplemented with various amounts of potassium iodide up to 260 mg/liter in drinking water to generate conditions ranging from severe iodine deficiency to severe iodine excess. In DHPN-treated rats, both conditions significantly increased thyroid follicular tumorigenesis. In DHPN-untreated rats, iodine deficiency produced diffuse thyroid hyperplasia, characterized by small follicles with tall epithelium and reduced colloid, together with a decrease in thyroxine (T4) and an increase in thyroid-stimulating hormone (TSH). On the other hand, iodine excess produced colloid goiter, characterized by large follicles with flat epithelium and abundant colloid admixed with normal or small-sized follicles lined by epithelium of normal height, together with normal serum T4 and slightly decreased TSH. These effects were directly proportional to the severity of iodine deficiency or extent of iodine excess and suggest that each condition has a different thyroid tumor promotion mechanism. Iodine intakes that showed the least tumor promotion were 2.6 and 9.7 mug/rat/day in this study. Promoting mechanisms and the problem of statistically estimating recommended daily iodine intake range are briefly discussed. RP KANNO, J (reprint author), NIEHS,MAIL DROP C2-09,POB 12233,111 ALEXANDER DR,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 37 Z9 43 U1 1 U2 6 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 1992 VL 20 IS 2 BP 226 EP 235 PG 10 WC Pathology; Toxicology SC Pathology; Toxicology GA JX901 UT WOS:A1992JX90100009 PM 1475583 ER PT J AU BOORMAN, GA MCDONALD, MR IMOTO, S PERSING, R AF BOORMAN, GA MCDONALD, MR IMOTO, S PERSING, R TI RENAL LESIONS INDUCED BY OCHRATOXIN-A EXPOSURE IN THE F344 RAT SO TOXICOLOGIC PATHOLOGY LA English DT Article DE MYCOTOXINS; CANCER; RENAL CARCINOMA; TUBULAR CELL CARCINOMA; CARCINOGENESIS; KIDNEY; ENVIRONMENTAL CARCINOGENS; TOXICITY; ADENOMA; NEOPLASIA AB Groups of 80 male and female F344 rats were exposed by gavage to ochratoxin A, a naturally occurring mycotoxin, at levels of 21, 70, and 210 mug/kg body weight for up to 2 years. Ochratoxin A induced non-neoplastic renal tubular epithelial changes consisting of cytoplasmic alteration, karyomegaly, degeneration, and cysts. Exposure-related renal tubular proliferative lesions included focal hyperplasia, tubular cell adenoma, and tubular cell carcinoma. Renal tubular cell adenoma occurred as early as 9 months in 1 high-dose male rat, and both adenomas and carcinomas were seen in males by 15 months. At the terminal sacrifice, renal tubular cell tumors were found in both male and female rats, but the response was more pronounced in the males. The incidence of renal tumors in the high-dose rats was the highest of any National Toxicology Program (NTP) study completed to date. In the high-dose males approximately one-third of the renal carcinomas developed metastases. This study demonstrates that ochratoxin A is a potent renal carcinogen in the F344 rat and suggests that contamination of feedstuff by this mycotoxin may pose a potential hazard to domestic animals and man. RP BOORMAN, GA (reprint author), NIEHS,NATL TOXICOL PROGRAM,CHEM CARCINOGENESIS BRANCH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 84 Z9 84 U1 1 U2 3 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 1992 VL 20 IS 2 BP 236 EP 245 PG 10 WC Pathology; Toxicology SC Pathology; Toxicology GA JX901 UT WOS:A1992JX90100010 PM 1475584 ER PT J AU WAALKES, MP CHERIAN, MG WARD, JM GOYER, RA AF WAALKES, MP CHERIAN, MG WARD, JM GOYER, RA TI IMMUNOHISTOCHEMICAL EVIDENCE OF HIGH-CONCENTRATIONS OF METALLOTHIONEIN IN PANCREATIC HEPATOCYTES INDUCED BY CADMIUM IN RATS SO TOXICOLOGIC PATHOLOGY LA English DT Article DE METAPLASIA; TRANSDIFFERENTIATION; CHEMICALLY INDUCED; RODENTS; METAL-BINDING PROTEIN AB A recent study from our laboratory has shown that cadmium, a toxic heavy metal, is one of the most effective agents known for inducing hepatocytic transdifferentiation of the rat pancreas. With repeated injections of cadmium, the incidence of rats with pancreatic hepatocytic foci can be as high as 93%. Cadmium is also well known as a very potent inducer of metallothionein. a metal-binding protein that appears to be important in the biologic response to several toxic heavy, metals in most tissues, including the pancreas. Therefore, the present study sought to determine if metallothionein was associated with cadmium-induced transdifferentiation of pancreatic cells. Expression of metallothionein was studied immunohistochemically by the peroxidase-antiperoxidase method in tissue sections of the pancreas of rats with pancreatic hepatocytes. High levels of metallothionein were localized primarily within the pancreatic hepatocytes. Surrounding normal pancreatic islet and acinar cells were not immunoreactive. Thus, metallothionein is expressed actively in cells transdifferentiated to hepatocytes by cadmium within the pancreas. RP WAALKES, MP (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,INORGAN CARCINOGENESIS SECT,FREDERICK,MD 21702, USA. NR 0 TC 10 Z9 11 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 1992 VL 20 IS 3 BP 323 EP 326 PN 1 PG 4 WC Pathology; Toxicology SC Pathology; Toxicology GA KM691 UT WOS:A1992KM69100002 PM 1295063 ER PT J AU THOMPSON, MB AF THOMPSON, MB TI CLINICAL PATHOLOGY IN THE NATIONAL-TOXICOLOGY-PROGRAM SO TOXICOLOGIC PATHOLOGY LA English DT Article; Proceedings Paper CT INTERNATIONAL WORKSHOP ON CLINICAL PATHOLOGY TESTING IN PRECLINICAL SAFETY ASSESSMENT / 1991 NATIONAL MEETING OF THE AMERICAN ASSOC FOR CLINICAL CHEMISTRY CY JUL 27, 1991 CL GEORGE WASHINGTON UNIV, WASHINGTON, DC SP AMER ASSOC CLIN CHEM, DIV ANIM CLIN CHEM, MILES, BOEHRINGER MANNHEIM, SORONO BAKER DIAGNOST, SOC TOXICOL PATHOLOGISTS, GEORGE WASHINGTON UNIV, PROCTER & GAMBLE HO GEORGE WASHINGTON UNIV DE STANDARDIZATION; HEMATOLOGY; CLINICAL CHEMISTRY; FISCHER-344 RAT; B6C3F(1) MOUSE; CONTROL DATA AB The National Toxicology Program (NTP) developed a standard approach for clinical pathology investigations that was integrated into most toxicity studies designed and conducted after 1986. Protocols for these studies include specific hematology and clinical chemistry analyses at 3 selected time points in 13-wk studies. Requirements concerning the anesthetization of animals, collection and analysis of samples, and reporting of results have been established to control sources of variability within and between contract laboratories that perform these studies for the NTP. Laboratories must meet minimum standards to be approved for participation in the Program. Important areas of consideration for these laboratories to perform clinical pathology investigations include the facility, equipment, personnel, performance, and quality control procedures. Clinical pathology results from approximately 60 13-wk studies that have been conducted by the NTP in 7 laboratories since 1987 are being analyzed to generate a database of control values for the Fischer rat and B6C3F1 mouse and to identify sources of variability. Experimental data from these studies are being analyzed and correlated with histopathologic findings to evaluate the contribution of clinical pathology to the characterization of toxicity and to examine the appropriateness of the current approach. Efforts such as these will provide for the evolution and continued relevance of clinical pathology in toxicity testing. RP THOMPSON, MB (reprint author), NIEHS,POB 12233,MAIL DROP C2-08,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 1992 VL 20 IS 3 BP 484 EP 489 PN 2 PG 6 WC Pathology; Toxicology SC Pathology; Toxicology GA KM693 UT WOS:A1992KM69300005 PM 1296277 ER PT J AU KANNO, J AF KANNO, J TI CLINICAL PATHOLOGY TESTING REGULATORY CONCERNS SO TOXICOLOGIC PATHOLOGY LA English DT Article; Proceedings Paper CT INTERNATIONAL WORKSHOP ON CLINICAL PATHOLOGY TESTING IN PRECLINICAL SAFETY ASSESSMENT / 1991 NATIONAL MEETING OF THE AMERICAN ASSOC FOR CLINICAL CHEMISTRY CY JUL 27, 1991 CL GEORGE WASHINGTON UNIV, WASHINGTON, DC SP AMER ASSOC CLIN CHEM, DIV ANIM CLIN CHEM, MILES, BOEHRINGER MANNHEIM, SORONO BAKER DIAGNOST, SOC TOXICOL PATHOLOGISTS, GEORGE WASHINGTON UNIV, PROCTER & GAMBLE HO GEORGE WASHINGTON UNIV DE REGULATIONS; ANIMALS; HEMATOLOGY; CLINICAL CHEMISTRY; TOXICITY TESTING AB In toxicity testing, each animal may have to be viewed as a surrogate for millions of people and should be examined as thoroughly as a human patient. However, there are many differences between human diagnosis and animal toxicity testing. Human diagnosis is primarily based on anamnesis, symptoms, and utilization of a huge database of diseases. However, in animal toxicity testing, clinical and anatomical pathology data are usually a primary source of toxicity information, even though the positive endpoints are generally not known in advance and the number of positive toxicity endpoints may be numerous. This situation will generate at least 2 practical problems in clinical pathology testing: (1) how to preselect test items without precise knowledge of toxicity endpoints and (2) how to handle multiple data sets for toxicity detection. The latter includes issues of inflation of the overall false-positive rate and multicomparison problems. A ''disease'' called ''significantosis'' and a concept of integrated interpretation of multiple biologically related items to avoid false-positive judgments and unnecessary censoring of meaningful outlier data are briefly discussed. In general, toxicity tests are quite exploratory and the endpoints are unknown and multiple, so the procedures for data interpretation should be determined on a case-by-case basis. Construction of toxicity entity-oriented databases may be a requirement for further refinement of toxicity study interpretation. RP KANNO, J (reprint author), NIEHS,ETB,DTRT MD C2-09,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 1992 VL 20 IS 3 BP 534 EP 537 PN 2 PG 4 WC Pathology; Toxicology SC Pathology; Toxicology GA KM693 UT WOS:A1992KM69300015 PM 1296287 ER PT J AU BRYANT, BJ JOKINEN, MP EUSTIS, SL THOMPSON, MB ABDO, KM AF BRYANT, BJ JOKINEN, MP EUSTIS, SL THOMPSON, MB ABDO, KM TI TOXICITY OF MONOCHLOROACETIC ACID ADMINISTERED BY GAVAGE TO F344 RATS AND B6C3F1 MICE FOR UP TO 13 WEEKS SO TOXICOLOGY LA English DT Article DE MONOCHLOROACETIC ACID; F344 RATS; B6C3F1 MICE; ACONITASE; CARDIOMYOPATHY ID DOSE LEVELS; METABOLISM; MOUSE AB Groups of 20 rats and 20 mice of each sex were administered monochloroacetic acid (MCAA) once daily, 5 days per week, in water by gavage for up to 13 weeks. Doses used were 0, 30, 60, 90, 120, or 150 mg/kg for rats and 0, 25, 50, 100, 150, or 200 mg/kg for mice. Compound-related deaths occurred at the four highest dose levels in rats and at the highest dose level in mice. Mean body weights of treated groups of rats and n-mice surviving until the end of the study were similar to those of the controls. A dose-related increase in blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, as well as a dose-related increase in the relative liver and kidney weights was observed in rats but not in mice. A dose-related increase in the incidence and severity of cardiomyopathy occurred in rats. This lesion may be related to the inhibition of heart mitochondrial aconitase activity. No compound-related lesions were observed in mice. The results of this study indicate that F344 rats are more sensitive than B6C3F1 mice; sexes within the species were equally sensitive. The no-observable-effect level was estimated as 30 mg MCAA/kg body weight for rats and 100 mg MCAA/kg body weight for mice. C1 NIEHS,MAIL DROP A0-01,POB 12233,RES TRIANGLE PK,NC 27709. NR 25 TC 14 Z9 16 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 PY 1992 VL 72 IS 1 BP 77 EP 87 DI 10.1016/0300-483X(92)90087-U PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA HH393 UT WOS:A1992HH39300007 PM 1539174 ER PT J AU MORRISSEY, RE HARRIS, MW DILIBERTO, JJ BIRNBAUM, LS AF MORRISSEY, RE HARRIS, MW DILIBERTO, JJ BIRNBAUM, LS TI LIMITED PCB ANTAGONISM OF TCDD-INDUCED MALFORMATIONS IN MICE SO TOXICOLOGY LETTERS LA English DT Article DE TCDD; PCBS; CLEFT PALATE; HYDRONEPHROSIS; ANTAGONISM; MICE ID C57BL/6N MICE; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; TOXICITY AB C57BL/6N mice, used to model induction of cleft palate and kidney malformations in offspring following maternal treatment with TCDD, were dosed on gestation day (gd) 9 with 2,2', 4,4', 5,5'-hexachlorobiphenyl (HCB) (62.5, 125, 250, 500, 1000 mg/kg) and/or gd 10 with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (15 or 18-mu-g/kg) to investigate the potential protective effects of HCB against TCDD-induced teratogenicity. Maternal body weight gain was increased by combinations of 15-mu-g TCDD/kg and 125-500 mg HCB/kg and decreased at doses of 15-mu-g TCDD/kg + 1000 HCB mg/kg. At the doses used in this study, there was no effect of either compound on number of live or dead offspring. Fetal body weight was slightly decreased in all groups dosed with greater-than-or-equal-to 250 mg HCB/kg. HCB did not induce cleft palate at a dose of 1000 mg/kg, but did induce increases in hydronephrosis and hydroureter at 500 and 1000 mg/kg. Combinations of HCB and TCDD decreased the incidence of cleft palate induced by TCDD alone, but only at doses of 15-mu-g TCDD/kg combined with 125-500 mg HCB/kg. The antagonism of hydronephrosis (incidence and severity) appeared over a narrower dose range (15-mu-g TCDD/kg + 500 mg HCB/kg). HCB induced increases (3-fold) in ethoxyresorufin-O-deethylase (EROD) activity at doses of 500 and 1000 mg/kg, suggesting that the limited antagonism of TCDD teratogenicity by HCB could be under the control of the Ah-receptor. C1 NIEHS,SYST TOXICOL BRANCH,RES TRIANGLE PK,NC 27709. NR 12 TC 46 Z9 47 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD JAN PY 1992 VL 60 IS 1 BP 19 EP 25 DI 10.1016/0378-4274(92)90043-J PG 7 WC Toxicology SC Toxicology GA HC093 UT WOS:A1992HC09300003 PM 1539179 ER PT B AU RAFFAELE, KC HAXBY, JV SCHAPIRO, MB AF RAFFAELE, KC HAXBY, JV SCHAPIRO, MB BE RACAGNI, G MENDLEWICZ, J TI AGE-ASSOCIATED MEMORY IMPAIRMENT SO TREATMENT OF AGE-RELATED COGNITIVE DYSFUNCTION : PHARMACOLOGICAL AND CLINICAL EVALUATION SE INTERNATIONAL ACADEMY FOR BIOMEDICAL AND DRUG RESEARCH LA English DT Proceedings Paper CT WORKSHOP ON TREATMENT OF AGE-RELATED COGNITIVE DYSFUNCTION : PHARMACOLOGICAL AND CLINICAL EVALUATION CY OCT 03-05, 1991 CL MONTE CARLO, MONACO SP COMMISS EUROPEAN COMMUNITIES RP RAFFAELE, KC (reprint author), NIA,NEUROSCI LAB,BLDG 10,RM 6C414,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 1 U2 1 PU KARGER PI BASEL PA BASEL BN 3-8055-5551-2 J9 INT ACAD B JI Int.Acad.Biomed.Drug Res. PY 1992 VL 2 BP 69 EP 79 PG 11 WC Geriatrics & Gerontology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA BV50H UT WOS:A1992BV50H00007 ER PT J AU HIGGINS, CF GOTTESMAN, MM AF HIGGINS, CF GOTTESMAN, MM TI IS THE MULTIDRUG TRANSPORTER A FLIPPASE SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID RESISTANT TUMOR-CELLS; P-GLYCOPROTEIN; GENE-PRODUCT; DOXORUBICIN; EXPRESSION; BINDING; LOCALIZATION; VINBLASTINE; COLCHICINE; PROTEIN AB The phenomenon of multidrug resistance is correlated with the presence of a membrane protein, P-glycoprotein, which pumps a wide variety of drugs out of cells thus reducing their toxicity. However, the mechanism of this pumping action remains unclear. In this article, we suggest that several properties of the multidrug transporter may be explained if it acts as a 'flippase' to transport drugs from the inner leaflet of the lipid bilayer to the outer or to the external medium. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. RP HIGGINS, CF (reprint author), UNIV OXFORD,JOHN RADCLIFFE HOSP,INST MOLEC MED,IMPERIAL CANC RES FUND LABS,OXFORD OX3 9DU,ENGLAND. NR 35 TC 622 Z9 630 U1 1 U2 18 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD JAN PY 1992 VL 17 IS 1 BP 18 EP 21 DI 10.1016/0968-0004(92)90419-A PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HD360 UT WOS:A1992HD36000006 PM 1374941 ER PT J AU MORSE, RH AF MORSE, RH TI TRANSCRIBED CHROMATIN SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID RNA POLYMERASE-II; NUCLEOSOME STRUCTURE; REVERSIBLE CHANGES; C-FOS; DNA; INVITRO; INVIVO; INITIATION; GENES; DISSOLUTION AB In eukaryotes, DNA that is transcribed is packaged first into nucleosomes and then into chromatin fibres. How does transcription proceed through chromatin? Studies of transcription through nucleosomes in vitro suggest that the intracellular environment may provide factors which alleviate the inhibitory effect that nucleosomes have on transcription, possibly via positive supercoiling induced by the migrating polymerase. Stable changes in nucleosome structure have been correlated with transcriptionally active chromatin, but the precise mechanism by which RNA polymerase transcribes through nucleosomal DNA remains unknown. RP MORSE, RH (reprint author), NIDDK,BETHESDA,MD 20892, USA. OI Morse, Randall/0000-0003-0000-8718 NR 34 TC 62 Z9 62 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD JAN PY 1992 VL 17 IS 1 BP 23 EP 26 DI 10.1016/0968-0004(92)90422-6 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HD360 UT WOS:A1992HD36000010 PM 1585452 ER PT J AU LUNN, G SANSONE, EB AF LUNN, G SANSONE, EB TI SAFE DISPOSAL OF DIAMINOBENZIDINE SO TRENDS IN GENETICS LA English DT Note RP LUNN, G (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ENVIRONM CONTROL & RES PROGRAM,FREDERICK,MD 21701, USA. FU PHS HHS [N01-C0-74102] NR 5 TC 1 Z9 2 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD JAN PY 1992 VL 8 IS 1 BP 7 EP 7 DI 10.1016/0168-9525(92)90006-P PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GX558 UT WOS:A1992GX55800005 PM 1369737 ER PT J AU PASCUALLEONE, A COHEN, LG HALLETT, M AF PASCUALLEONE, A COHEN, LG HALLETT, M TI CORTICAL MAP PLASTICITY IN HUMANS SO TRENDS IN NEUROSCIENCES LA English DT Letter ID HUMAN MOTOR CORTEX; MAGNETIC STIMULATION RP PASCUALLEONE, A (reprint author), NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,HUMAN CORT PHYSIOL,BETHESDA,MD 20892, USA. NR 19 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD JAN PY 1992 VL 15 IS 1 BP 13 EP 14 DI 10.1016/0166-2236(92)90341-5 PG 2 WC Neurosciences SC Neurosciences & Neurology GA GY956 UT WOS:A1992GY95600006 PM 1374951 ER PT B AU HAYUNGA, EG SUMNER, MP DUNCAN, JF CHAKRABARTI, EK WEBERT, DW AF HAYUNGA, EG SUMNER, MP DUNCAN, JF CHAKRABARTI, EK WEBERT, DW BE WILLIAMS, JC KOCAN, KM GIBBS, EPJ TI PRODUCTION OF ANTIIDIOTYPIC ANTIBODIES AS POTENTIAL IMMUNOREAGENTS FOR THE SEROLOGICAL DIAGNOSIS OF BOVINE CYSTICERCOSIS SO TROPICAL VETERINARY MEDICINE : CURRENT ISSUES PERSPECTIVES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Proceedings Paper CT 1ST BIENNIAL CONF OF THE AMERICAN SOC OF TROPICAL VETERINARY MEDICINE CY FEB 05-08, 1991 CL SAN JUAN, PR SP AMER SOC TROP VET MED, ADV INSTRUMENTS, CARIBBEAN BIORES, MAYAGUEZ DAIRY, MERCK SHARP & DOHME, NICOLAS CARRILLO CORREA, PITMAN MOORE, RHONE MERIEUX LAB, SCHERING PLOUGH ANIM HLTH, UPJOHN RP HAYUNGA, EG (reprint author), NIH,DIV RES GRANTS,BETHESDA,MD 20892, USA. NR 0 TC 12 Z9 13 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA NEW YORK BN 0-89766-728-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1992 VL 653 BP 178 EP 183 DI 10.1111/j.1749-6632.1992.tb19642.x PG 6 WC Parasitology; Veterinary Sciences SC Parasitology; Veterinary Sciences GA BW42Y UT WOS:A1992BW42Y00021 PM 1626868 ER PT J AU ISHIHARA, C MIYAZAWA, M NISHIO, J AZUMA, I CHESEBRO, B AF ISHIHARA, C MIYAZAWA, M NISHIO, J AZUMA, I CHESEBRO, B TI USE OF LOW TOXICITY ADJUVANTS AND KILLED VIRUS TO INDUCE PROTECTIVE IMMUNITY AGAINST THE FRIEND MURINE LEUKEMIA RETROVIRUS-INDUCED DISEASE SO VACCINE LA English DT Article DE ADJUVANTS; LOW TOXICITY; FRIEND MURINE LEUKEMIA; RETROVIRUS ID MONOPHOSPHORYL LIPID-A; HOST GENETIC-CONTROL; STRUCTURAL DETERMINATION; INDUCED ERYTHROLEUKEMIA; GUINEA-PIGS; LEUKEMIA; RESPONSES; VACCINES; H-2; 6-O-ACYL-MURAMYLDIPEPTIDES AB Low toxic and synthetic adjuvants were investigated in the induction of protective immunity against Friend murine retrovirus-induced erythroleukaemia by immunization with inactivated Friend murine leukaemia helper virus (F-MuLV). 6-O-(2-tetradecyl-hexadecanoyl)-N-acetylmuramyl-L-alanyl-D-isoglutamine (B30-MDP) showed a significant enhancement of the protective immunity against Friend virus-induced erythroleukaemia not only in H-2a/b mice known to make good immune responses to F-MuLV envelope, but also in H-2a/a mice which are usually unable to respond to F-MuLV envelope protein. Another analogue of N-acetylmuramyl-D-isoglutamine (MDP), N(alpha)-acetylmuramyl-L-alanyl-D-isoglutaminyl-N(epsilon)-stearoyl-L-lysine [MDP-Lys(L18)], which has been shown to enhance non-specific protective activity against bacterial and viral infections, however, showed no adjuvant activity in the present system. A combined adjuvant of the synthesized mycobacterial cord factor, trehalose dimycolate (TDM) and detoxified bacterial endotoxin, monophosphoryl lipid A from Salmonella minnesota, gave good protection which was comparable to complete Freund's adjuvant in both H-2a/b and H-2a/a mice. C1 US PHS,NATL INST ALLERGY & INFECT DIS,PERSISTENT VIRAL DIS,ROCKY MTN LABS,HAMILTON,MT 59840. HOKKAIDO UNIV,INST IMMUNOL SCI,SAPPORO,HOKKAIDO 060,JAPAN. NR 32 TC 14 Z9 14 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PY 1992 VL 10 IS 5 BP 353 EP 356 DI 10.1016/0264-410X(92)90378-W PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA HL423 UT WOS:A1992HL42300013 PM 1574922 ER PT J AU GORSE, GJ BELSHE, RB NEWMAN, FK FREY, SE AF GORSE, GJ BELSHE, RB NEWMAN, FK FREY, SE TI LYMPHOCYTE PROLIFERATIVE RESPONSES FOLLOWING IMMUNIZATION WITH HUMAN-IMMUNODEFICIENCY-VIRUS RECOMBINANT GP160 SO VACCINE LA English DT Article DE LYMPHOCYTE PROLIFERATION; HUMAN IMMUNODEFICIENCY VIRUS; RECOMBINANT GP160; CELL-MEDIATED IMMUNITY ID ENVELOPE GLYCOPROTEIN; AIDS VIRUS; CELLS AB Following immunization of healthy adult volunteers with baculovirus-derived HIV-1 gp160 vaccine (rgp160), we measured lymphocyte proliferation to rgp160, the V3 loop peptide of gp160, control proteins, and phytohaemagglutinin. Four persons received injections of 40-mu-g or 80-mu-g doses of rgp160 vaccine at times 0, and 1, 6 and 18 months; one additional volunteer received only three injections of vaccine. Vaccination with rgp160 induced lymphocyte proliferative responses to rgp160, but not to V3 loop peptide. Repeated injection of rgp160 even at low doses induced a cellular immune response which was not attributable to T-cell recognition of the V3 loop peptide. C1 VET AFFAIRS MED CTR,ST LOUIS,MO. NIH,BIOMED ENGN & INSTRUMENTAT BRANCH,BETHESDA,MD 20892. RP GORSE, GJ (reprint author), ST LOUIS UNIV,SCH MED,DEPT INTERNAL MED,DIV INFECT DIS,1402 S GRAND BLVD,ST LOUIS,MO 63104, USA. FU NIAID NIH HHS [N01-AI-05064] NR 19 TC 36 Z9 36 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PY 1992 VL 10 IS 6 BP 383 EP 388 DI 10.1016/0264-410X(92)90068-U PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA HP781 UT WOS:A1992HP78100006 PM 1534641 ER PT J AU CONNORS, M COLLINS, PL FIRESTONE, CY SOTNIKOV, AV WAITZE, A DAVIS, AR HUNG, PP CHANOCK, RM MURPHY, BR AF CONNORS, M COLLINS, PL FIRESTONE, CY SOTNIKOV, AV WAITZE, A DAVIS, AR HUNG, PP CHANOCK, RM MURPHY, BR TI COTTON RATS PREVIOUSLY IMMUNIZED WITH A CHIMERIC RSV FG GLYCOPROTEIN DEVELOP ENHANCED PULMONARY PATHOLOGY WHEN INFECTED WITH RSV, A PHENOMENON NOT ENCOUNTERED FOLLOWING IMMUNIZATION WITH VACCINIA RSV RECOMBINANTS OR RSV SO VACCINE LA English DT Article DE RESPIRATORY SYNCYTIAL VIRUS; VACCINE; RECOMBINANT; INACTIVATED; ENHANCED PULMONARY HISTOPATHOLOGY; COTTON RATS ID RESPIRATORY SYNCYTIAL VIRUS; FUSION F; INFANTS; CHILDREN AB In studies conducted in the 1960s, children previously immunized with a formalin-inactivated respiratory syncytial virus (RSV) vaccine (FI-RSV) developed a greater incidence and severity of pulmonary disease during subsequent natural RSV infection than did controls. It was previously shown that cotton rats immunized with FI-RSV or immunoaffinity-purified fusion (F) glycoprotein developed enhanced pulmonary histopathology following intranasal challenge with RSV. In the present studies, various forms of immunization, including parenteral inoculation of an immunoaffinity-purified F glycoprotein or a chimeric FG glycoprotein produced in insect cells using a baculovirus vector (Bac-FG), intradermal infection with a vaccinia-F recombinant (Vac-F) or intranasal infection with an adenovirus-F recombinant (Ad-F) or RSV, were compared for immunogenicity, efficacy and ability to alter the host so that enhanced pulmonary histopathology developed during RSV infection 3 months after immunization. Immunization of cotton rats with F glycoprotein, Bac-FG, Vac-F, Ad-F or infection with RSV induced high levels of ELISA-F antibodies, but the antibodies induced by purified F glycoprotein of Bac-FG had low levels of neutralizing activity. Immunization with Vac-F or Ad-F, or infection with RSV induced a high level of resistance to pulmonary RSV replication, whereas animals immunized with Bac-FG or FI-RSV were only partially protected. Following RSV challenge, animals immunized with purified F glycoprotein or Bac-FG developed the highest levels of bronchiolar and alveolar histopathology, those immunized with FI-RSV had intermediate levels, and those immunized with Vac-F or RSV had histopathology scores at control levels. Ad-F immunized animals had elevated scores of bronchiolar but not alveolar histopathology, however, this finding was not reproducible. Passive transfer of pooled immune sera from animals infected with RSV or Vac-F and Vac-G was highly protective, whereas pooled sera from animals immunized with Bac-FG failed to protect the lungs against RSV challenge. Increased pulmonary histopathology was not observed in the passively immunized animals following RSV challenge, suggesting that the histopathology was mediated by RSV-specific T cells. These data indicate that subunit F glycoprotein or chimeric FG vaccines share with FI-RSV the properties of (i) induction of F antibodies with low neutralizing activity and (ii) enhancement of pulmonary histopathology during subsequent RSV infection. These observations confirm the need for caution in studies involving the administration of RSV subunit vaccines to seronegative humans. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,MOLEC BIOL LAB,BOSTON,MA 02115. WYETH AYERST RES,DIV BIOTECHNOL & MICROBIOL,PHILADELPHIA,PA 19101. RP CONNORS, M (reprint author), NIAID,INFECT DIS LAB,RESP VIRUSES SECT,BLDG 7,ROOM 106,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 28 TC 99 Z9 100 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PY 1992 VL 10 IS 7 BP 475 EP 484 DI 10.1016/0264-410X(92)90397-3 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA HV884 UT WOS:A1992HV88400009 PM 1609551 ER PT J AU CIZNAR, I AHSAN, CR RAHMAN, A SHAHABUDDIN, M BARTKOVA, G CLEMENS, JD SACK, DA AF CIZNAR, I AHSAN, CR RAHMAN, A SHAHABUDDIN, M BARTKOVA, G CLEMENS, JD SACK, DA TI CROSSED IMMUNOELECTROPHORETIC ANALYSIS OF ANTIGENIC COMPOSITION OF B-SUBUNIT WHOLE-CELL AND WHOLE-CELL ONLY KILLED ORAL CHOLERA VACCINES SO VACCINE LA English DT Article DE CHOLERA; ORAL VACCINE; B-SUBUNIT WHOLE-CELL; WHOLE-CELL ONLY; CROSSED IMMUNOELECTROPHORESIS; ANTIGENS ID VIBRIO-CHOLERAE; OUTER-MEMBRANE; ADULT-RABBITS; FIELD-TRIAL; IMMUNIZATION; ANTIBACTERIAL; IMMUNITY; TOXIN; PROTEINS; FIMBRIAE AB Crossed immunoelectrophoresis was used to identify antigens preserved in the whole-cell component of oral cholera vaccines tested in the field trial in Bangladesh. The composition and immunogenicity of the vaccine antigens were compared with those of antigens obtained from live cells of Vibrio cholerae 01 of both biovars and serovars. The whole-cell component of the vaccine contained ten antigens in comparison with the live Vibrio cells which revealed the presence of 30 antigens. The whole-cell component contained lipopolysaccharide, flagellar antigen, one cell-bound haemagglutinin and at least six outer membrane protein antigens. C1 INT CTR DIARRHOEL DIS RES,DHAKA,BANGLADESH. NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. RP CIZNAR, I (reprint author), INST PREVENT & CLIN MED,LIMBOVA 14,CS-83301 BRATISLAVA,CZECHOSLOVAKIA. NR 38 TC 1 Z9 1 U1 0 U2 1 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PY 1992 VL 10 IS 9 BP 591 EP 596 DI 10.1016/0264-410X(92)90438-P PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA JB961 UT WOS:A1992JB96100005 PM 1502836 ER PT J AU KARZON, DT BOLOGNESI, DP KOFF, WC AF KARZON, DT BOLOGNESI, DP KOFF, WC TI DEVELOPMENT OF A VACCINE FOR THE PREVENTION OF AIDS, A CRITICAL-APPRAISAL SO VACCINE LA English DT Review DE AIDS; HIV; VACCINE DEVELOPMENT; CLINICAL TRIALS; PATHOGENESIS; ANIMAL MODELS; ETHICAL LEGAL ISSUES ID HUMAN-IMMUNODEFICIENCY-VIRUS; RECOMBINANT GLYCOPROTEIN GP120; HUMAN MONOCLONAL-ANTIBODY; ENVELOPE GLYCOPROTEIN; T-CELLS; NEUTRALIZING ANTIBODIES; HTLV-III/LAV; IMMUNOLOGICAL ADJUVANTS; CANDIDATE VACCINE; TYPE-1 INFECTION AB The Pathogenesis and clinical expression of HIV-1 infection in humans is considered in terms of classical pathogenetic studies of viral infections for which successful vaccines have been produced. The unique features of HIV pathogenesis are defined, and gaps in knowledge identified as a framework for considering designs for immune intervention. Envelope-derived candidate vaccines have been used in immunization and challenge experiments in SIV/macaque or HIV/chimpanzee models, presented either as vaccinia recombinant vectors or as subunits, singly or in sequence. These studies have been paralleled by clinical trials for safety and immunogenicity in seronegative individuals. Data generated will permit comparison of immune responses to specific antigens and delivery systems in animal models and in humans. In limited studies conducted under optimized conditions, non-human primates have been protected against virus challenge when immunized with some candidate vaccines or following passive transfer of high-titred antibody. Consideration of current information suggests that in order to prevent HIV infection it may be necessary to devise new strategies capable of inducing and maintaining high threshold titres of biologically relevant antibody as well as persistence of active cytotoxic T cells recognizing multiple epitopes. C1 DUKE UNIV,MED CTR,DEPT SURG,DURHAM,NC 27710. NIAID,DIV AIDS,ROCKVILLE,MD 20892. RP KARZON, DT (reprint author), VANDERBILT UNIV,MED CTR,SCH MED,DEPT PEDIAT & MICROBIOL & IMMUNOL,NASHVILLE,TN 37232, USA. NR 107 TC 27 Z9 27 U1 0 U2 1 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PY 1992 VL 10 IS 14 BP 1039 EP 1052 DI 10.1016/0264-410X(92)90114-Y PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA JY397 UT WOS:A1992JY39700010 PM 1281948 ER PT J AU EMERSON, SU HUANG, YK MCRILL, C LEWIS, M SHAPIRO, M LONDON, WT PURCELL, RH AF EMERSON, SU HUANG, YK MCRILL, C LEWIS, M SHAPIRO, M LONDON, WT PURCELL, RH TI MOLECULAR-BASIS OF VIRULENCE AND GROWTH OF HEPATITIS-A VIRUS IN CELL-CULTURE SO VACCINE LA English DT Article; Proceedings Paper CT INTERNATIONAL SYMP ON ACTIVE IMMUNIZATION AGAINST HEPATITIS-A CY JAN 27-29, 1992 CL VIENNA, AUSTRIA DE VIRUS MUTANTS; CELL CLONES; TRANSFECTION; DISEASE ID COMPLETE NUCLEOTIDE-SEQUENCE; PROPAGATION; ADAPTATION; CDNA AB The ability of engineered variants of hepatitis A virus (strain HM175) to replicate in cell culture or to cause disease in marmosets was evaluated. Virus variants were encoded by chimeric genomes constructed from infectious cDNA clones of two viruses (wild type and cell-culture-adapted) which differed in their ability to grow in vitro and to cause acute hepatitis in marmosets. Transfection and infectivity assays indicated that virus growth in vitro could be enhanced by subcloning the cell substrate prior to infection or by introducing multiple combinations of two or more mutations into the wild type genome. Various chimeric viruses induced liver enzyme elevations in marmosets, indicating that attenuation of virulence also required multiple mutations. C1 BIOQUAL INC,ROCKVILLE,MD 20853. GEORGETOWN UNIV,ROCKVILLE,MD 20853. RP EMERSON, SU (reprint author), NIAID,INFECT DIS LAB,HEPATITIS VIRUS SECT,BETHESDA,MD 20892, USA. NR 8 TC 7 Z9 7 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PY 1992 VL 10 SU 1 BP S36 EP S39 DI 10.1016/0264-410X(92)90539-V PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA JY978 UT WOS:A1992JY97800011 PM 1335656 ER PT J AU KATTAMIS, C SCHIFF, E MAUER, W FIEREZ KOFF, R FROSNER, G OGRADY, J NISHIOKA, K BALAYAN, M MELNICK, J KANE, M PURCELL, R STAPLETON, J SIEGL, G LEMON, S EMERSON, S HOLLINGER, B FLEHMIG, B PURCELL, R SKINNER, GRB HADZIYANNIS, S AF KATTAMIS, C SCHIFF, E MAUER, W FIEREZ KOFF, R FROSNER, G OGRADY, J NISHIOKA, K BALAYAN, M MELNICK, J KANE, M PURCELL, R STAPLETON, J SIEGL, G LEMON, S EMERSON, S HOLLINGER, B FLEHMIG, B PURCELL, R SKINNER, GRB HADZIYANNIS, S TI VIROLOGY AND CLINICAL ASPECTS OF HEPATITIS-A - DISCUSSION SO VACCINE LA English DT Discussion C1 UNIV MIAMI,SCH MED,DEPT HEPATOL,1500 NW 12TH AVE,SUITE 1101,MIAMI,FL 33136. VET ADM MED CTR,CTR LIVER DIS,MIAMI,FL 33125. METROW MED CTR,DEPT MED,FRAMINGHAM,MA 01701. KINGS COLL HOSP,INST LIVER STUDIES,LONDON SE5 9PJ,ENGLAND. MOSCOW POLIOMYELITIS & VIRAL ENCEPHALITIDES INST,MOSCOW 142782,USSR. BAYLOR COLL MED,DIV MOLEC VIROL,HOUSTON,TX 77030. IOWA CITY VA MED CTR,DEPT INTERNAL MED,IOWA CITY,IA 52242. UNIV IOWA,COLL MED,DEPT INTERNAL MED,IOWA CITY,IA 52242. INST CLIN MICROBIOL & IMMUNOL,CH-9000 ST GALLEN,SWITZERLAND. UNIV N CAROLINA,DEPT MED,CHAPEL HILL,NC 27599. NIAID,INFECT DIS LAB,HEPATITIS VIRUS SECT,BETHESDA,MD 20892. WHO,DIV COMMUNICABLE DIS,MICROBIOL & IMMUNOL SUPPORT SERV,CH-1211 GENEVA 27,SWITZERLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PY 1992 VL 10 SU 1 BP S53 EP S55 PG 3 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA JY978 UT WOS:A1992JY97800015 ER PT J AU LAUFS PURCELL, R MELNICK, J KRUGMAN, S AF LAUFS PURCELL, R MELNICK, J KRUGMAN, S TI PROTECTIVE EFFICACY TRIALS - DISCUSSION SO VACCINE LA English DT Discussion C1 NIAID,INFECT DIS LAB,BLDG 7,ROOM 202,BETHESDA,MD 20892. BAYLOR COLL MED,DIV MOLEC VIROL,HOUSTON,TX 77030. NYU MED CTR,NEW YORK,NY 10016. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PY 1992 VL 10 SU 1 BP S169 EP S169 PG 1 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA JY978 UT WOS:A1992JY97800049 ER PT J AU PURCELL, RH DHONDT, E BRADBURY, R EMERSON, SU GOVINDARAJAN, S BINN, L AF PURCELL, RH DHONDT, E BRADBURY, R EMERSON, SU GOVINDARAJAN, S BINN, L TI INACTIVATED HEPATITIS-A VACCINE - ACTIVE AND PASSIVE IMMUNOPROPHYLAXIS IN CHIMPANZEES SO VACCINE LA English DT Article; Proceedings Paper CT INTERNATIONAL SYMP ON ACTIVE IMMUNIZATION AGAINST HEPATITIS-A CY JAN 27-29, 1992 CL VIENNA, AUSTRIA DE IMMUNOPROPHYLAXIS; HEPATITIS-A VIRUS; ANIMAL MODEL; IMMUNOGLOBULIN ID NEUTRALIZING ANTIBODY; VIRUS AB Studies of active and passive immunoprophylaxis were carried out in chimpanzees to determine whether a candidate hepatitis A virus (HAV) vaccine could stimulate antibody to HAV (anti-HAV) that was qualitatively similar to anti-HAV stimulated by natural infection. Normal immune globulin (Ig) was prepared from plasma obtained from human volunteers before and after vaccination with the HAV vaccine, and these preparations or commercially prepared Ig were administered to chimpanzees. Protective efficacy was compared to that obtained after vaccination of chimpanzees. As expected, pre-vaccination Ig did not protect chimpanzees against challenge with virulent hepatitis A. In contrast, chimpanzees were protected against hepatitis A by Ig prepared from volunteers who had received hepatitis A vaccine. The protection was qualitatively similar to that afforded by commercial normal Ig containing convalescent anti-HAV. The minimum protective dose of passively acquired anti-HAV was approximately the minimum dose detectable by serological means. This information will be useful in calculating minimum acceptable titres of anti-HAV in normal Ig. Whereas administration of Ig protected chimpanzees against hepatitis A pathology, it did not protect them from infection with HAV. Thus, these chimpanzees were protected by classical passive-active immunoprophylaxis. In contrast, chimpanzees actively immunized with HAV vaccine were apparently protected against both hepatitis A pathology and HAV infection. The mechanism of this complete protection is unknown but may simply represent the higher titre of anti-HAV in the vaccinated chimpanzees, compared to the passively protected animals. C1 SMITHKLINE BEECHAM BIOL,RIXENSART,BELGIUM. BIOQUAL INC,ROCKVILLE,MD. RANCHO LOS AMIGOS MED CTR,DOWNEY,CA 90242. WALTER REED ARMY INST RES,WASHINGTON,DC 20307. RP PURCELL, RH (reprint author), NIAID,INFECT DIS LAB,BLDG 7,ROOM 202,BETHESDA,MD 20892, USA. NR 7 TC 32 Z9 33 U1 0 U2 2 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PY 1992 VL 10 SU 1 BP S148 EP S151 DI 10.1016/0264-410X(92)90572-2 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA JY978 UT WOS:A1992JY97800044 PM 1335648 ER PT J AU SJOGREN, MH PURCELL, RH MCKEE, K BINN, L MACARTHY, P TICEHURST, J FEINSTONE, S CAUDILL, J SEE, A HOKE, C BANCROFT, W DHONDT, E AF SJOGREN, MH PURCELL, RH MCKEE, K BINN, L MACARTHY, P TICEHURST, J FEINSTONE, S CAUDILL, J SEE, A HOKE, C BANCROFT, W DHONDT, E TI CLINICAL AND LABORATORY OBSERVATIONS FOLLOWING ORAL OR INTRAMUSCULAR ADMINISTRATION OF A LIVE ATTENUATED HEPATITIS-A VACCINE CANDIDATE SO VACCINE LA English DT Article; Proceedings Paper CT INTERNATIONAL SYMP ON ACTIVE IMMUNIZATION AGAINST HEPATITIS-A CY JAN 27-29, 1992 CL VIENNA, AUSTRIA DE HEPATITIS-A; VIRAL HEPATITIS; LIVER ID VIRUS; ANTIBODY AB Clinical observations made after immunising volunteers with a live attenuated hepatitis A vaccine are described. The candidate vaccine was prepared with the HM175 strain of hepatitis A virus and shown to be safe, immunogenic and efficacious in experimental animals. When the candidate vaccine was tested by oral administration in humans at increasing doses - 10(4), 10(5), 10(6) and 10(7) median tissue culture infective doses ( TCID50) - an antibody response was not observed at any dose. Volunteers who received similar doses by the intramuscular route developed antibody to hepatitis A three weeks after immunization with 10(6) or 10(7) TCID50. The antibody response was sustained for the 12 weeks of the observation period. All volunteers remained healthy with normal results from liver tests throughout the monitoring period. Further clinical observations of this product are in progress. C1 NIH,BETHESDA,MD 20892. WALTER REED ARMY INST RES,WASHINGTON,DC 20307. US FDA,ROCKVILLE,MD 20857. SMITHKLINE BEECHAM BIOL,RIXENSART,BELGIUM. RP SJOGREN, MH (reprint author), USA,MED RES INST INFECT DIS,DIV MED,FREDERICK,MD 21702, USA. RI Ticehurst, John/I-7532-2012 NR 7 TC 20 Z9 20 U1 0 U2 1 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PY 1992 VL 10 SU 1 BP S135 EP S137 DI 10.1016/0264-410X(92)90568-5 PG 3 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA JY978 UT WOS:A1992JY97800040 PM 1335645 ER PT J AU MUENCHAU, DD RUSCETTI, S ANDERSON, WF AF MUENCHAU, DD RUSCETTI, S ANDERSON, WF TI SEQUENCES PRESENT IN A SMALL REGION OF THE AKV VIRUS ENVELOPE GENE DETERMINE THE EFFICIENCY WITH WHICH PSEUDOTYPED SPLEEN FOCUS-FORMING VIRUS INFECTS ERYTHROID TARGET-CELLS SO VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; NUCLEOTIDE-SEQUENCE; VERTEBRATE CELLS; FRIEND-LEUKEMIA; ERYTHROLEUKEMIA; RECOMBINATION; CULTURE; INVITRO; BURSTS; DNA C1 NHLBI,MOLEC HEMATOL BRANCH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NCI,GENET LAB,BETHESDA,MD 20892. NR 27 TC 2 Z9 2 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JAN PY 1992 VL 186 IS 1 BP 161 EP 166 DI 10.1016/0042-6822(92)90070-6 PG 6 WC Virology SC Virology GA GU994 UT WOS:A1992GU99400016 PM 1309273 ER PT J AU LAL, RB RUDOLPH, DL KAPLAN, JE HJELLE, B LEVINE, PH COLIGAN, JE VISCIDI, RP AF LAL, RB RUDOLPH, DL KAPLAN, JE HJELLE, B LEVINE, PH COLIGAN, JE VISCIDI, RP TI IDENTIFICATION OF IMMUNODOMINANT EPITOPES IN ENVELOPE GLYCOPROTEIN OF HUMAN LYMPHOTROPIC-T VIRUS TYPE-II SO VIROLOGY LA English DT Article ID CELL LEUKEMIA; HTLV-I; MONOCLONAL-ANTIBODY; SYNTHETIC PEPTIDES; SEQUENCE; INFECTION; PROTEIN; REGIONS; GP21 C1 NCI,BETHESDA,MD 20817. UNIV NEW MEXICO,SCH MED,DEPT PATHOL,ALBUQUERQUE,NM 87131. NIAID,BIOL RESOURCES BRANCH,BETHESDA,MD 20894. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,ENDOWOOD DIV INFECT DIS,BALTIMORE,MD 21205. RP LAL, RB (reprint author), CTR DIS CONTROL,NATL CTR INFECT DIS DIV VIRAL & RICKETTSIAL DIS,ATLANTA,GA 30333, USA. NR 32 TC 16 Z9 16 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JAN PY 1992 VL 186 IS 1 BP 274 EP 279 DI 10.1016/0042-6822(92)90081-Y PG 6 WC Virology SC Virology GA GU994 UT WOS:A1992GU99400027 PM 1727602 ER PT J AU OBERSTE, MS GONDA, MA AF OBERSTE, MS GONDA, MA TI CONSERVATION OF AMINO-ACID-SEQUENCE MOTIFS IN LENTIVIRUS VIF PROTEINS SO VIRUS GENES LA English DT Article DE VIF; LENTIVIRUS; SEQUENCE; MOTIF; ANALYSIS ID HUMAN-IMMUNODEFICIENCY-VIRUS; NUCLEOTIDE-SEQUENCE; AIDS VIRUS; GENOME ORGANIZATION; GENE NOMENCLATURE; HIV-1; TAT AB The nonstructural/regulatory genes of human immunodeficiency virus type I (HIV-1) and other lentiviruses are believed to play an important role in the replication and pathogenesis of these viruses. In HIV-1 and other lentiviruses, the vif (viral infectivity factor) open reading frame (ORF) (also termed sor or Q in some lentivirus genomes) is located in the central region, overlapping the 3' end of the pol ORF, but in a different reading frame. Among the lentiviruses, only equine infectious anemia virus lacks a vif ORF. The predicted Vif protein sequences from 38 lentiviruses were analyzed for the presence of global and local sequence similarity. The Vif proteins of closely related lentiviruses are highly conserved (HIV-1HXB2:HIV-1mn = 91% identity), while those of more distantly related lentirviruses have diverged significantly (HIV-1HXB2:simian immunodeficiency virus(mac) = 30% identity). A search for local sequence similarity revealed that a unifying feature of predicted lentivirus Vif proteins is the presence of at least one of two short, highly conserved sequence motifs, SL(I/V)X4YX9Y and SLQXLA. SLQXLA was present in 34 of 38 lentiviruses examined, while the remaining four lentiviruses had one (three viruses) or two (one virus) substitutions in this motif (of five total substitutions, three were conservative changes). The SL(I/V)X4YX9Y motif was found only in primate lentiviruses and in bovine immunodeficiency-like virus. Based on these findings, we suggest that the locus designation vif be used to denote all lentivirus ORFs previously called vif, Q, or sor. RP OBERSTE, MS (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,DYNCORP,CELL & MOLEC STRUCT,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 28 TC 129 Z9 130 U1 1 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0920-8569 J9 VIRUS GENES JI Virus Genes PD JAN PY 1992 VL 6 IS 1 BP 95 EP 102 DI 10.1007/BF01703760 PG 8 WC Genetics & Heredity; Virology SC Genetics & Heredity; Virology GA HB446 UT WOS:A1992HB44600008 PM 1312756 ER PT J AU ANDOLSEK, L BRINTON, L CHONGSUVIVATWONG, V FERRAZ, E GREEN, A HAGENFELDT, K HULKA, B KELSEY, J MEHTA, S RAMOS, R ROSENBERG, L SCHLESSELMAN, J SHAABAN, M STANFORD, J THOMAS, D AF ANDOLSEK, L BRINTON, L CHONGSUVIVATWONG, V FERRAZ, E GREEN, A HAGENFELDT, K HULKA, B KELSEY, J MEHTA, S RAMOS, R ROSENBERG, L SCHLESSELMAN, J SHAABAN, M STANFORD, J THOMAS, D TI ORAL-CONTRACEPTIVES AND NEOPLASIA SO WHO TECHNICAL REPORT SERIES LA English DT Review ID INVASIVE CERVICAL-CANCER; BENIGN BREAST DISEASE; EPITHELIAL OVARIAN-CANCER; CUTANEOUS MALIGNANT-MELANOMA; EXOGENOUS FEMALE HORMONES; LOS-ANGELES-COUNTY; LONG-TERM USE; RISK-FACTORS; YOUNG-WOMEN; ENDOMETRIAL CANCER C1 EDVARD KARDELJ UNIV, DEPT OBSTET & GYNAECOL, YU-61000 LJUBLJANA, YUGOSLAVIA. NCI, ENVIRONM STUDIES SECT, BETHESDA, MD 20892 USA. PRINCE SONGKLA UNIV, FAC MED, EPIDEMIOL UNIT, HAT YAI, THAILAND. UNIV BRASILIA, DEPT OBSTET & GYNAECOL, BR-70910 BRASILIA, DF, BRAZIL. QUEENSLAND INST MED RES, HERSTON, QLD 4006, AUSTRALIA. KAROLINSKA HOSP, DEPT OBSTET & GYNAECOL, S-10401 STOCKHOLM 60, SWEDEN. UNIV N CAROLINA, SCH PUBL HLTH, DEPT EPIDEMIOL, CHAPEL HILL, NC 27514 USA. COLUMBIA UNIV, DIV EPIDEMIOL, NEW YORK, NY 10027 USA. INDIAN COUNCIL MED RES, NEW DELHI, INDIA. DR JOSE FABELLA MEM HOSP, DEPT OBSTET & GYNAECOL, MANILA, PHILIPPINES. DR JOSE FABELLA MEM HOSP, REPROD HLTH PROGRAMMES, MANILA, PHILIPPINES. BOSTON UNIV, SCH MED, SLONE EPIDEMIOL UNIT, BROOKLINE, MA USA. UNIFORMED SERV UNIV HLTH SCI, DEPT PREVENT MED & BIOMETR, BETHESDA, MD 20814 USA. UNIV ASSIUT, DEPT OBSTET & GYNAECOL, ASSIUT, EGYPT. FRED HUTCHINSON CANC RES CTR, PROGRAM EPIDEMIOL, SEATTLE, WA 98104 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 198 TC 0 Z9 0 U1 0 U2 0 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA MARKETING AND DISSEMINATION, CH-1211 GENEVA 27, SWITZERLAND SN 0512-3054 J9 WHO TECH REP SER JI WHO Tech. Rep. Ser. PY 1992 IS 817 BP 1 EP 46 PG 46 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA HW002 UT WOS:A1992HW00200001 ER PT J AU AXELL, T CHIMIMBA, PC EKLUND, SA LOE, H MAHER, R MASON, D SONGPAISAN, Y TAKAZOE, I BARMES, DE PILOT, T TODD, J WAGNER, V AF AXELL, T CHIMIMBA, PC EKLUND, SA LOE, H MAHER, R MASON, D SONGPAISAN, Y TAKAZOE, I BARMES, DE PILOT, T TODD, J WAGNER, V TI RECENT ADVANCES IN ORAL HEALTH SO WHO TECHNICAL REPORT SERIES LA English DT Article C1 UNIV LUND,SCH DENT,FAC ODONTOL,S-21401 MALMO,SWEDEN. MINIST HLTH,HLTH SERV,LILONGWE,MALAWI. UNIV MICHIGAN,SCH PUBL HLTH,PROGRAM DENT PUBL HLTH,ANN ARBOR,MI 48109. NIDR,BETHESDA,MD 20892. JINNAH POSTGRAD MED CTR,DEPT DENT,KARACHI,PAKISTAN. GLASGOW DENT HOSP & SCH,GLASGOW,SCOTLAND. MAHIDOL UNIV,FAC PUBL HLTH,DEPT EPIDEMIOL,BANGKOK 10700,THAILAND. TOKYO DENT COLL,DEPT MICROBIOL,CHIBA,JAPAN. TOKYO DENT COLL,POSTGRAD SCH,CHIBA,JAPAN. WHO,CH-1211 GENEVA 27,SWITZERLAND. UNIV GRONINGEN,WHO,COLLABORATING CTR ORAL HLTH SERV RES,9700 AB GRONINGEN,NETHERLANDS. DENT PRACTICE BOARD,EASTBOURNE,E SUSSEX,ENGLAND. UNIV UPPSALA,CTR HUMAN COMP STUDIES,S-75105 UPPSALA,SWEDEN. NR 34 TC 0 Z9 0 U1 0 U2 4 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA DISTRIBUTION AND SALES, CH-1211 GENEVA 27, SWITZERLAND SN 0512-3054 J9 WHO TECH REP SER JI Who Techn. Rep. Ser. PY 1992 IS 826 BP 1 EP 37 PG 37 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA KP681 UT WOS:A1992KP68100001 ER PT J AU DENNIS, DT DREYER, G ISMAIL, MM KUMARASWAMI, V MAK, JW MATAIKA, JU OTTESEN, EA PIESSENS, WF RAJAGOPALAN, PK SOUTHGATE, BA HUIJIN, Z AF DENNIS, DT DREYER, G ISMAIL, MM KUMARASWAMI, V MAK, JW MATAIKA, JU OTTESEN, EA PIESSENS, WF RAJAGOPALAN, PK SOUTHGATE, BA HUIJIN, Z TI LYMPHATIC FILARIASIS - THE DISEASE AND ITS CONTROL SO WHO TECHNICAL REPORT SERIES LA English DT Article ID BRUGIA-MALAYI; BANCROFTIAN FILARIASIS; MONOCLONAL-ANTIBODY; DIETHYLCARBAMAZINE; TRANSMISSION; IVERMECTIN; EFFICACY; ASSAY; MODEL; TRIAL C1 CTR DIS CONTROL,DIV VECTOR BORNE INFECT DIS,BACTERIAL ZOONOSES BRANCH,FT COLLINS,CO 80522. FIOCRUZ MS,AGGEU MAGALHAES RES CTR,RECIFE,BRAZIL. UNIV COLOMBO,FAC MED,COLOMBO,SRI LANKA. TB RES CTR,MADRAS,INDIA. INST MED RES,DIV MALARIA & FILARIASIS RES,KUALA LUMPUR,MALAYSIA. TAMAVUA HOSP,WELLCOME VIRUS LAB,FIJI FILARIASIS PROGRAMME,SUVA,FIJI. NIAID,CLIN PARASITOL SECT,PARASIT DIS LAB,BETHESDA,MD 20892. HARVARD UNIV,SCH PUBL HLTH,DEPT TROP PUBL HLTH,BOSTON,MA 02115. VECTOR CONTROL RES CTR,PONDICHERRY,INDIA. UNIV LONDON LONDON SCH HYG & TROP MED,LONDON WC1E 7HT,ENGLAND. GUIZHOU PROV INST PARASIT DIS,DEPT FILARIASIS,GUIYANG,PEOPLES R CHINA. RI Mak, Joon Wah/C-9174-2011 OI Mak, Joon Wah/0000-0002-2538-0797 NR 26 TC 0 Z9 0 U1 0 U2 0 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA DISTRIBUTION AND SALES, CH-1211 GENEVA 27, SWITZERLAND SN 0512-3054 J9 WHO TECH REP SER JI Who Techn. Rep. Ser. PY 1992 IS 821 BP 1 EP 71 PG 71 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA JZ411 UT WOS:A1992JZ41100001 ER PT J AU ALLANDER, E BENEVOLENSKAJA, LI BENNETT, JC BRANDT, KD CHAHADE, WH CHENG, CN DIEPPE, P GORDIS, L HOMMA, M MALAVIYA, AN MENKES, CJ MOUTSOPOULOS, HM MUIRDEN, KD NACHEMSON, AL NASSONOVA, VA PLOTZ, CM SCOTT, JT SHULMAN, LE VILLIAUMEY, J AF ALLANDER, E BENEVOLENSKAJA, LI BENNETT, JC BRANDT, KD CHAHADE, WH CHENG, CN DIEPPE, P GORDIS, L HOMMA, M MALAVIYA, AN MENKES, CJ MOUTSOPOULOS, HM MUIRDEN, KD NACHEMSON, AL NASSONOVA, VA PLOTZ, CM SCOTT, JT SHULMAN, LE VILLIAUMEY, J TI RHEUMATIC DISEASES SO WHO TECHNICAL REPORT SERIES LA English DT Article C1 HUDDINGE UNIV HOSP,DEPT SOCIAL MED,S-14186 HUDDINGE,SWEDEN. ACAD MED SCI USSR,INST RHEUMATOL,MOSCOW 109801,USSR. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. INDIANA UNIV,SCH MED,DIV RHEUMATOL,INDIANAPOLIS,IN 46202. SAO PAULO STATE PUBL HOSP,RHEUMATOL SERV,SAO PAULO,BRAZIL. BEIJING UNION MED COLL HOSP,RHEUMATOL,BEIJING,PEOPLES R CHINA. UNIV BRISTOL,DEPT MED,BRISTOL BS8 1TH,AVON,ENGLAND. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21218. KEIO UNIV,SCH MED,DEPT INTERNAL MED,TOKYO 108,JAPAN. ALL INDIA INST MED SCI,DEPT MED,CLIN IMMUNOL SERV,NEW DELHI 110016,INDIA. HOP COCHIN,DEPT RHEUMATOL,F-75674 PARIS 14,FRANCE. UNIV MELBOURNE,DEPT MED,RHEUMATOL UNIT,PARKVILLE,VIC 3052,AUSTRALIA. GOTHENBURG UNIV,DEPT ORTHOPAED,S-41124 GOTHENBURG,SWEDEN. SUNY DOWNSTATE MED CTR,DEPT MED,NEW YORK,NY. CHARING CROSS HOSP,DEPT RHEUMATOL,LONDON W6 8RP,ENGLAND. NIAMSD,BETHESDA,MD. HOP HENRI MONDOR,INT LEAGUE AGAINST RHEUMATISM,F-94010 CRETEIL,FRANCE. UNIV IOANNINA,DEPT INTERNAL MED,IOANNINA,GREECE. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA DISTRIBUTION AND SALES, CH-1211 GENEVA 27, SWITZERLAND SN 0512-3054 J9 WHO TECH REP SER JI Who Techn. Rep. Ser. PY 1992 IS 816 BP R6 EP & PG 0 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA HW001 UT WOS:A1992HW00100001 ER PT J AU SMOUSE, PE LONG, JC AF SMOUSE, PE LONG, JC TI MATRIX CORRELATION-ANALYSIS IN ANTHROPOLOGY AND GENETICS SO YEARBOOK OF PHYSICAL ANTHROPOLOGY LA English DT Review DE MANTEL TEST; GENETIC AFFINITY; MIGRATION; CLINAL VERSUS CLUSTER VARIATION ID SPATIAL AUTO-CORRELATION; PAPUA-NEW-GUINEA; SNAIL CEPAEA-NEMORALIS; 3 TIME PERIODS; GEOGRAPHIC-VARIATION; DISTANCE MATRICES; YANOMAMA INDIANS; MULTIVARIATE-ANALYSIS; EUROPEAN POPULATIONS; MULTIPLE-REGRESSION AB The comparative analysis of the population variation patterns exhibited by different types of information has long been a genuine anthropological/genetic preoccupation. One of the generic problems attracting repeated attention is the connection between genetic and cultural consequences of population isolation; we expect both patterns and amounts of variation to reflect the same history of group fission and fusion, but what do we see in practice? Numerous techniques have been employed in such work, all based on comparison of different matrices of pairwise distances/affinities. A basic difficulty with all of these methods is that the N(N - 1) pairwise elements of an (N x N) matrix cannot be mutually independent. Recently, a versatile test of matrix correlation that allows for this fact, originally developed by Mantel but since extensively modified and extended, has gained popularity in anthropology, as well as geography, ecology, sociology, psychometrics, population biology, and systematics. We present here a general framework for many of these efforts, based on the Mantel test, and then illustrate its use with four examples from our own work and that of our colleagues: a) genetic affinity and migrational separation in the Bainwa, b) clinal versus cluster variation in the Yanomama, c) genetic, linguistic, and geographic affinities among the Chibcha-speaking tribes, and d) migration and genetic affinity in the Gainj and Kalam. The technique is nonparametric and so general that it is useful for many different types of pattern comparison, even when the connections between different types of information are poorly understood. Greater analytic potential is generally realized when there are definite theoretical connections between the patterns being compared. With theoretical care and a bit of imagination, one can combine the advantages of parametric assumptions with the robustness of nonparametric analysis. Novel analyses and anthropological opportunities are emerging continuously. C1 RUTGERS STATE UNIV,COOK COLL,CTR THEORET & APPL GENET,NEW BRUNSWICK,NJ 08903. UNIV NEW MEXICO,DEPT ANTHROPOL,ALBUQUERQUE,NM 87131. NIAAA,NEUROGENET LAB,BETHESDA,MD 20892. NR 122 TC 129 Z9 132 U1 1 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0096-848X J9 YEARB PHYS ANTHROPOL JI Yearb. Phys. Anthrop. PY 1992 VL 35 BP 187 EP 213 PG 27 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA KC967 UT WOS:A1992KC96700006 ER PT J AU DEMENT, JM RINGEN, K SELIKOFF, IJ EGILMAN, D GIBBS, G KILBURN, K CASE, B RICHTER, E LILIS, R AF DEMENT, JM RINGEN, K SELIKOFF, IJ EGILMAN, D GIBBS, G KILBURN, K CASE, B RICHTER, E LILIS, R TI CARCINOGENICITY OF CHRYSOTILE ASBESTOS - EVIDENCE FROM COHORT STUDIES SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID MANUFACTURING FRICTION MATERIALS; DUST EXPOSURE; OCCUPATIONAL EPIDEMIOLOGY; VERMICULITE MINERS; MORTALITY; WORKERS; TREMOLITE; TEXTILE; CONDUCT; CANCER C1 NATL HLTH & SAFETY FUND,WASHINGTON,DC. MT SINAI MED CTR,NEW YORK,NY 10029. BROWN UNIV,PROVIDENCE,RI 02912. UNIV SO CALIF,LOS ANGELES,CA 90089. UNIV PITTSBURGH,PITTSBURGH,PA 15260. HEBREW UNIV JERUSALEM,JERUSALEM,ISRAEL. RP DEMENT, JM (reprint author), NIEHS,11 ALEXANDER DR,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 36 TC 13 Z9 13 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD DEC 31 PY 1991 VL 643 BP 15 EP 26 DI 10.1111/j.1749-6632.1991.tb24440.x PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM568 UT WOS:A1991JM56800002 PM 1809127 ER PT J AU GREENE, R SCHAEFER, CM OLIVER, LC DEMENT, J LILIS, R FINKELSTEIN, M GAMSU, G MARKOVITZ, A CASE, B SELIKOFF, IJ KRONENBERG, R ERNST, P AF GREENE, R SCHAEFER, CM OLIVER, LC DEMENT, J LILIS, R FINKELSTEIN, M GAMSU, G MARKOVITZ, A CASE, B SELIKOFF, IJ KRONENBERG, R ERNST, P TI IMPROVED DETECTION OF ASBESTOS-RELATED PLEURAL PLAQUES WITH DIGITAL RADIOGRAPHY SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. HANNOVER MED SCH,W-3000 HANNOVER 61,GERMANY. NIEHS,RES TRIANGLE PK,NC 27709. CUNY MT SINAI SCH MED,NEW YORK,NY 10029. ONTARIO MINIST LABOR,TORONTO,ONTARIO,CANADA. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. UNIV SO CALIF,SCH MED,LOS ANGELES,CA 90033. UNIV PITTSBURGH,PITTSBURGH,PA 15260. UNIV TEXAS,CTR HLTH,TYLER,TX. MCGILL UNIV,MONTREAL H3A 2T5,QUEBEC,CANADA. RP GREENE, R (reprint author), MASSACHUSETTS GEN HOSP,DEPT OCCUPAT MED,BOSTON,MA 02114, USA. NR 6 TC 1 Z9 2 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD DEC 31 PY 1991 VL 643 BP 90 EP 99 DI 10.1111/j.1749-6632.1991.tb24448.x PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM568 UT WOS:A1991JM56800008 PM 1809179 ER PT J AU LASKY, JA BONNER, JC BRODY, AR AF LASKY, JA BONNER, JC BRODY, AR TI THE PATHOBIOLOGY OF ASBESTOS-INDUCED LUNG-DISEASE - A PROPOSED ROLE FOR MACROPHAGE-DERIVED GROWTH-FACTORS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID SHORT-TERM EXPOSURE; ALVEOLAR MACROPHAGES; TRITIATED-THYMIDINE; DEPOSITION PATTERN; FACTOR HOMOLOG; RATS; INHALATION; FIBERS; PROLIFERATION; ACCUMULATION RP LASKY, JA (reprint author), NIEHS,PULM PATHOBIOL LAB,RES TRIANGLE PK,NC 27709, USA. NR 27 TC 3 Z9 3 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD DEC 31 PY 1991 VL 643 BP 239 EP 244 DI 10.1111/j.1749-6632.1991.tb24468.x PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM568 UT WOS:A1991JM56800023 PM 1809136 ER PT J AU MARTINEZ, M PRICE, SR MOSS, J ALVAREZGONZALEZ, R AF MARTINEZ, M PRICE, SR MOSS, J ALVAREZGONZALEZ, R TI MONO(ADP-RIBOSYL)ATION OF POLY(ADP-RIBOSE)POLYMERASE BY CHOLERA-TOXIN SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ADP-RIBOSYLATION FACTOR; ADENYLATE-CYCLASE; RIBOSYLTRANSFERASE ACTIVITY; REGULATORY COMPONENT; SOLUBLE-PROTEINS; BINDING PROTEINS; NUCLEOTIDE; GTP; PURIFICATION; SYNTHETASE C1 TEXAS COLL OSTEOPATH MED,UNT,DEPT MICROBIOL & IMMUNOL,FT WORTH,TX 76107. NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892. FU NCRR NIH HHS [2S07RR05879-08] NR 37 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 31 PY 1991 VL 181 IS 3 BP 1412 EP 1418 DI 10.1016/0006-291X(91)92096-3 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GX736 UT WOS:A1991GX73600072 PM 1764092 ER PT J AU SESTI, G MARINI, MA TULLIO, AN MONTEMURRO, A BORBONI, P FUSCO, A ACCILI, D LAURO, R AF SESTI, G MARINI, MA TULLIO, AN MONTEMURRO, A BORBONI, P FUSCO, A ACCILI, D LAURO, R TI ALTERED EXPRESSION OF THE 2 NATURALLY-OCCURRING HUMAN INSULIN-RECEPTOR VARIANTS IN ISOLATED ADIPOCYTES OF NON-INSULIN-DEPENDENT DIABETES-MELLITUS PATIENTS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID GENE C1 NIDDK,DIABET BRANCH,BETHESDA,MD. RP SESTI, G (reprint author), UNIV ROMA TOR VERGATA,DIPARTIMENTO MED INTERNA,ROME,ITALY. RI Sesti, Giorgio/B-1509-2012; OI Sesti, Giorgio/0000-0002-1618-7688 NR 14 TC 44 Z9 44 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 31 PY 1991 VL 181 IS 3 BP 1419 EP 1424 DI 10.1016/0006-291X(91)92097-4 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GX736 UT WOS:A1991GX73600073 PM 1764093 ER PT J AU DIPASQUALE, B MARINI, AM YOULE, RJ AF DIPASQUALE, B MARINI, AM YOULE, RJ TI APOPTOSIS AND DNA-DEGRADATION INDUCED BY 1-METHYL-4-PHENYLPYRIDINIUM IN NEURONS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID DEATH C1 NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. RP DIPASQUALE, B (reprint author), NINCDS,SURG NEUROL BRANCH,BIOCHEM SECT,BETHESDA,MD 20892, USA. NR 10 TC 194 Z9 196 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 31 PY 1991 VL 181 IS 3 BP 1442 EP 1448 DI 10.1016/0006-291X(91)92101-O PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GX736 UT WOS:A1991GX73600077 PM 1764096 ER PT J AU CHAPEKAR, MS HUGGETT, AC CHENG, C AF CHAPEKAR, MS HUGGETT, AC CHENG, C TI DEXAMETHASONE PREVENTS THE GROWTH INHIBITORY EFFECTS OF RECOMBINANT TUMOR-NECROSIS-FACTOR IN A RAT HEPATOMA-CELL LINE REUBER-RC-3 - AN ASSOCIATION WITH THE CHANGES IN THE MESSENGER-RNA LEVELS FOR MULTIDRUG RESISTANCE GENE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ACUTE-PHASE PROTEINS; CYTO-TOXIC ACTIVITY; FACTOR-ALPHA; GAMMA-INTERFERON; INVITRO; INTERLEUKIN-1; INDUCTION; INVIVO; LIVER RP CHAPEKAR, MS (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 26 TC 14 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 31 PY 1991 VL 181 IS 3 BP 1524 EP 1531 DI 10.1016/0006-291X(91)92112-W PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GX736 UT WOS:A1991GX73600088 PM 1722406 ER PT J AU KUBOTA, S MITSUDOMI, T YAMADA, Y AF KUBOTA, S MITSUDOMI, T YAMADA, Y TI INVASIVE HUMAN FIBROSARCOMA DNA MEDIATED INDUCTION OF A 92 KDA GELATINASE TYPE-IV COLLAGENASE LEADS TO AN INVASIVE PHENOTYPE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID N-RAS GENE; TUMOR-CELLS; EXTRACELLULAR-MATRIX; METALLOPROTEINASES; FIBROBLASTS; EXPRESSION; INHIBITOR; SECRETE C1 UNIV OCCUPAT & ENVIRONM HLTH,SCH MED,DEPT SURG 2,KITAKYUSHU,FUKUOKA 807,JAPAN. RP KUBOTA, S (reprint author), NIDR,DEV BIOL LAB,BETHESDA,MD 20892, USA. OI Mitsudomi, Tetsuya/0000-0001-9860-8505 NR 24 TC 31 Z9 31 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 31 PY 1991 VL 181 IS 3 BP 1539 EP 1547 DI 10.1016/0006-291X(91)92114-Y PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GX736 UT WOS:A1991GX73600090 PM 1662501 ER PT J AU ROBERTS, K SHEVACH, EM AF ROBERTS, K SHEVACH, EM TI IMMUNOREGULATORY ROLE OF GAMMA-DELTA-T CELLS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID ANTIGEN RECEPTOR COMPLEX; CD8 LYMPHOCYTES-T; RECOGNITION; EXPRESSION; GENE; IDENTIFICATION; SPECIFICITY; HETERODIMER; HYBRIDOMA; PROTEINS RP ROBERTS, K (reprint author), NIAID,IMMUNOL LAB,BLDG 10,ROOM 11N315,BETHESDA,MD 20892, USA. NR 35 TC 8 Z9 8 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD DEC 30 PY 1991 VL 636 BP 1 EP 8 DI 10.1111/j.1749-6632.1991.tb33432.x PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM207 UT WOS:A1991JM20700001 PM 1724360 ER PT J AU ZACHARCHUK, CM MERCEP, M ASHWELL, JD AF ZACHARCHUK, CM MERCEP, M ASHWELL, JD TI THYMOCYTE ACTIVATION AND DEATH - A MECHANISM FOR MOLDING THE T-CELL REPERTOIRE SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID REACTIVE V-BETA-6+ CELLS; MONOCLONAL-ANTIBODY; DNA FRAGMENTATION; CYCLOSPORINE-A; GLUCOCORTICOID RECEPTOR; CAENORHABDITIS-ELEGANS; MEDIATED CYTOLYSIS; NEGATIVE SELECTION; ANTIGEN RECEPTOR; CLONAL DELETION RP ZACHARCHUK, CM (reprint author), NCI,BIOL RESPONSE MODIFIERS PROGRAM,BLDG 10,ROOM 13N-268,BETHESDA,MD 20892, USA. NR 60 TC 25 Z9 25 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD DEC 30 PY 1991 VL 636 BP 52 EP 70 DI 10.1111/j.1749-6632.1991.tb33438.x PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM207 UT WOS:A1991JM20700007 PM 1793231 ER PT J AU WEINER, HL ZHANG, ZJ KHOURY, SJ MILLER, A ALSABBAGH, A BROD, SA LIDER, O HIGGINS, P SOBEL, R NUSSENBLATT, RB HAFLER, DA AF WEINER, HL ZHANG, ZJ KHOURY, SJ MILLER, A ALSABBAGH, A BROD, SA LIDER, O HIGGINS, P SOBEL, R NUSSENBLATT, RB HAFLER, DA TI ANTIGEN-DRIVEN PERIPHERAL IMMUNE TOLERANCE - SUPPRESSION OF ORGAN-SPECIFIC AUTOIMMUNE-DISEASES BY ORAL-ADMINISTRATION OF AUTOANTIGENS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID MYELIN BASIC-PROTEIN; LIPOPOLYSACCHARIDE LPS REGULATION; COLLAGEN-INDUCED ARTHRITIS; II COLLAGEN; EPITHELIAL-CELLS; ENCEPHALOMYELITIS; INDUCTION; MICE; RATS C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. NEI,IMMUNOL LAB,BETHESDA,MD 20205. RP WEINER, HL (reprint author), BRIGHAM & WOMENS HOSP,CTR NEUROL DIS,75 FRANCIS ST,BOSTON,MA 02115, USA. OI khoury, samia/0000-0003-3198-6063 NR 21 TC 24 Z9 24 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD DEC 30 PY 1991 VL 636 BP 227 EP 232 DI 10.1111/j.1749-6632.1991.tb33454.x PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM207 UT WOS:A1991JM20700023 PM 1793212 ER PT J AU NEWELL, KA ELLENHORN, JDI HIRSCH, R BLUESTONE, JA AF NEWELL, KA ELLENHORN, JDI HIRSCH, R BLUESTONE, JA TI IMMUNOPOTENTIATION OF ANTIVIRAL AND ANTITUMOR IMMUNE-RESPONSES USING ANTI-T-CELL RECEPTOR ANTIBODIES AND MITOGENS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID STAPHYLOCOCCAL ENTEROTOXIN-B; HUMAN PERIPHERAL LYMPHOCYTES; CLASS-II MOLECULES; MONOCLONAL-ANTIBODY; ACTIVATION; INVIVO; MICE; STIMULATION; OKT3; INVITRO C1 UNIV CINCINNATI HOSP,DEPT SURG,CINCINNATI,OH 45208. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. UNIV CHICAGO,BEN MAY INST,COMMITTEE IMMUNOL,CHICAGO,IL 60637. RP NEWELL, KA (reprint author), UNIV CHICAGO HOSP & CLIN,DEPT SURG,DIV TRANSPLANTAT,CHICAGO,IL 60637, USA. FU NCI NIH HHS [P30 CA 14599, R01 CA 49260]; NIAID NIH HHS [P01 AI 29531] NR 36 TC 2 Z9 2 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD DEC 30 PY 1991 VL 636 BP 279 EP 287 DI 10.1111/j.1749-6632.1991.tb33458.x PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM207 UT WOS:A1991JM20700027 PM 1793214 ER PT J AU SEGAL, DM QIAN, JH ANDREW, SM TITUS, JA MEZZANZANICA, D GARRIDO, MA WUNDERLICH, JR AF SEGAL, DM QIAN, JH ANDREW, SM TITUS, JA MEZZANZANICA, D GARRIDO, MA WUNDERLICH, JR TI CYTOKINE RELEASE BY PERIPHERAL-BLOOD LYMPHOCYTES TARGETED WITH BISPECIFIC ANTIBODIES, AND ITS ROLE IN BLOCKING TUMOR-GROWTH SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID HUMAN T-CELLS; RECEPTOR ANTIBODIES; COLORIMETRIC ASSAY; MONONUCLEAR-CELLS; ACTIVATION; ANTI-T3; ADHESION; ANTIGEN; INVIVO; LYSIS RP SEGAL, DM (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B17,BETHESDA,MD 20892, USA. OI Mezzanzanica, Delia/0000-0002-9664-6871 NR 26 TC 4 Z9 4 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD DEC 30 PY 1991 VL 636 BP 288 EP 294 DI 10.1111/j.1749-6632.1991.tb33459.x PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM207 UT WOS:A1991JM20700028 PM 1793216 ER PT J AU LINDBERG, B LINDBERG, J PITHA, J RAO, CT HARATA, K AF LINDBERG, B LINDBERG, J PITHA, J RAO, CT HARATA, K TI SYNTHESIS OF SOME 2-O-(2-HYDROXYALKYL) AND 2-O-(2,3-DIHYDROXYALKYL) DERIVATIVES OF CYCLOMALTOHEPTAOSE SO CARBOHYDRATE RESEARCH LA English DT Article ID CYCLODEXTRIN DERIVATIVES AB On alkylation of cyclomaltoheptaose with oxiranes, promoted by alkali of low concentration, substitution at secondary positions, particularly at O-2, is favoured. The reaction has been used to prepare the 2-O-[(R)- and (S)-2-hydroxypropyl], 2-O-(2-hydroxy-2-methylpropyl), 2-O-[(R)- and (S)-2,3-dihydroxypropyl], and 2-O-[(R)- and (S)-2,3-dihydroxy-2-methylpropyl] derivatives. Each of these derivatives is less soluble in water than cyclomaltoheptaose, and their complexes with toluene, in contrast to that of cyclomaltoheptaose, are well soluble in water. C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RES INST POLYMERS & TEXT,TSUKUBA,IBARAKI 305,JAPAN. RP LINDBERG, B (reprint author), UNIV STOCKHOLM,ARRHENIUS LAB,DEPT ORGAN CHEM,S-10691 STOCKHOLM,SWEDEN. NR 9 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD DEC 30 PY 1991 VL 222 BP 113 EP 119 DI 10.1016/0008-6215(91)89010-D PG 7 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA GZ507 UT WOS:A1991GZ50700010 PM 1813102 ER PT J AU NIE, JY KIRK, KL AF NIE, JY KIRK, KL TI SYNTHESIS OF METABOLITES OF 6-FLUORO-DOPA SO JOURNAL OF FLUORINE CHEMISTRY LA English DT Article ID FLUORINATED NOREPINEPHRINES; O-METHYLATION; SITE AB Key metabolites of 6-fluoro-DOPA have been prepared by side-chain elaboration of 6-fluorovanillin and 6-fluoroveratraldehyde. C1 NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. NR 16 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE SA LAUSANNE PI LAUSANNE 1 PA PO BOX 564, 1001 LAUSANNE 1, SWITZERLAND SN 0022-1139 J9 J FLUORINE CHEM JI J. Fluor. Chem. PD DEC 30 PY 1991 VL 55 IS 3 BP 259 EP 269 DI 10.1016/S0022-1139(00)82354-4 PG 11 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic SC Chemistry GA HM826 UT WOS:A1991HM82600005 ER PT J AU ATAMNA, IZ ISSAQ, HJ MUSCHIK, GM JANINI, GM AF ATAMNA, IZ ISSAQ, HJ MUSCHIK, GM JANINI, GM TI OPTIMIZATION OF RESOLUTION IN CAPILLARY ZONE ELECTROPHORESIS - COMBINED EFFECT OF APPLIED VOLTAGE AND BUFFER CONCENTRATION SO JOURNAL OF CHROMATOGRAPHY LA English DT Article ID LIQUID-CHROMATOGRAPHY; SILICA CAPILLARIES; INFLUENCE MOBILITY; SEPARATIONS; PROTEINS; SELECTIVITY; TEMPERATURE; PARAMETERS; EFFICIENCY AB Expressions are formulated for the prediction of solute migration time and resolution as a function applied voltage and buffer concentration in capillary zone electrophoresis. The resolution equation assumes that solute diffusion is the only operative zone-broadening mechanism. A resolution surface in applied voltage and buffer concentration space is presented featuring isochrones that are used to predict the behavior of resolution under constant analysis time. In the resolution-voltage planes the resolution increases continuously with increasing voltage. At the high-voltage border, the resolution decreases continuously with increasing concentration, however, at the low-voltage border the resolution passes through a shallow maximum as the buffer concentration is increased. At constant analysis time, resolution is optimized by simultaneously increasing the voltage and the buffer concentration. In comparison, this theoretical approach, which predicts resolution from solute migration times only, gives values that are consistently about 40-50% higher than experimentally determined resolution. C1 NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,POB B,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74102] NR 27 TC 38 Z9 38 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR PD DEC 27 PY 1991 VL 588 IS 1-2 BP 315 EP 320 DI 10.1016/0021-9673(91)85039-I PG 6 WC Chemistry, Analytical SC Chemistry GA GZ704 UT WOS:A1991GZ70400039 PM 1818085 ER PT J AU LICHTI, U AF LICHTI, U TI HAIR FOLLICLE TRANSGLUTAMINASES SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID HUMAN EPIDERMAL TRANSGLUTAMINASE; BLOOD-COAGULATION FACTOR; PROTEIN-KINASE-C; KERATINOCYTE TRANSGLUTAMINASE; RETINOIC ACID; GUINEA-PIG; ENVELOPE FORMATION; SKIN; CELLS; EXPRESSION RP LICHTI, U (reprint author), NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892, USA. NR 33 TC 9 Z9 9 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD DEC 26 PY 1991 VL 642 BP 82 EP 99 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM212 UT WOS:A1991JM21200008 PM 1687305 ER PT J AU WEINBERG, WC BROWN, PD STETLERSTEVENSON, WG YUSPA, SH AF WEINBERG, WC BROWN, PD STETLERSTEVENSON, WG YUSPA, SH TI MODULATION OF HAIR FOLLICLE CELL-PROLIFERATION AND COLLAGENOLYTIC ACTIVITY BY SPECIFIC GROWTH-FACTORS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID FACTOR RECEPTORS; EXPRESSION; SKIN; METALLOPROTEINASES; MECHANISMS; INVASION; TISSUES; MATRIX; BETA; RNA C1 NCI,PATHOL LAB,BETHESDA,MD 20892. RP WEINBERG, WC (reprint author), NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BLDG 37,ROOM 3B25,BETHESDA,MD 20892, USA. RI Weinberg, Wendy/A-8920-2009; Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 17 TC 7 Z9 7 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD DEC 26 PY 1991 VL 642 BP 281 EP 290 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM212 UT WOS:A1991JM21200020 PM 1809087 ER PT J AU QUINN, TC KLINE, RL HALSEY, N HUTTON, N RUFF, A BUTZ, A BOULOS, R MODLIN, JF AF QUINN, TC KLINE, RL HALSEY, N HUTTON, N RUFF, A BUTZ, A BOULOS, R MODLIN, JF TI EARLY DIAGNOSIS OF PERINATAL HIV-INFECTION BY DETECTION OF VIRAL-SPECIFIC IGA ANTIBODIES SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; INFANTS BORN; CHILDREN; WOMEN; MOTHERS; AIDS; TRANSMISSION; TYPE-1; BLOOD AB Objectives. - To evaluate the clinical utility of a human immunodeficiency virus (HIV)-IgA serological assay for diagnosis of perinatally acquired HIV infection. Design. - Coded serum samples prospectively collected from children born to HIV-infected mothers and uninfected mothers were analyzed by HIV-IgA immunoblot. Setting. - A university hospital in Baltimore, Md, and an outpatient clinic in Port-au-Prince, Haiti. Population. - Five hundred thirty-nine serum samples were obtained sequentially from 278 children born to HIV-infected women (116 from The Johns Hopkins Hospital and 62 from Port-au-Prince) and from 42 control children born to HIV-seronegative children in Port-au-Prince. Outcome Measures. - Results from the HIV-IgA serological assays were compared with the known infection status of the child at 15 months of age as determined by the standard IgG Western blot and the clinical classification of the Centers for Disease Control. Sensitivity, specificity, and predictive values were calculated at different ages and collectively for children 3 months of age or older. Results. - The HIV-IgA assay was positive in one of six specimens from HIV-infected children under 1 month of age, six of nine specimens from infected children at 3 months of age, and 160 of 161 specimens from 47 HIV-infected children 6 months of age or older. Of 334 specimens from 243 uninfected children, 333 were negative by the HIV-IgA assay. The overall sensitivity and the specificity of the IgA assay for children older than 3 months of age were 97.6% and 99.7%, and the positive and negative predictive values were 99.4% and 98.7%, respectively. Conclusion. - Although the HIV-IgA assay had a low sensitivity within the first months of life, the high sensitivity, specificity, and predictive values of this assay demonstrate its utility for the diagnosis of perinatally acquired HIV infection after the third month of age. Early diagnosis with this relatively simple and inexpensive serological assay should aid in the implementation of antiviral therapy and provide useful information for the care of children born to HIV-infected mothers in both developing and developed countries. C1 CTR DEV & HLTH,PORT AU PRINCE,HAITI. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT INT HLTH,BALTIMORE,MD 21218. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NURSING,BALTIMORE,MD 21205. RP QUINN, TC (reprint author), JOHNS HOPKINS UNIV HOSP,BLALOCK 1111,600 N WOLFE ST,BALTIMORE,MD 21205, USA. FU PHS HHS [1R01A126521] NR 27 TC 81 Z9 81 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 25 PY 1991 VL 266 IS 24 BP 3439 EP 3442 DI 10.1001/jama.266.24.3439 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA GV878 UT WOS:A1991GV87800028 PM 1744957 ER PT J AU LANDESMAN, S WEIBLEN, B MENDEZ, H WILLOUGHBY, A GOEDERT, JJ RUBINSTEIN, A MINKOFF, H MOROSO, G HOFF, R AF LANDESMAN, S WEIBLEN, B MENDEZ, H WILLOUGHBY, A GOEDERT, JJ RUBINSTEIN, A MINKOFF, H MOROSO, G HOFF, R TI CLINICAL UTILITY OF HIV-IGA IMMUNOBLOT ASSAY IN THE EARLY DIAGNOSIS OF PERINATAL HIV-INFECTION SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; INVITRO PRODUCTION; INFANTS BORN; CHILDREN; ANTIBODY; MOTHERS; RISK AB Objective. - To ascertain the sensitivity, specificity, predictive value, and clinical use of a human immunodeficiency virus (HIV)-IgA immunoblot assay for diagnosing perinatal HIV infection in infants tested at birth to 1 month, 3 months, and 6 months of age. Design. - Prospective, longitudinal cohort study of children born to HIV-infected and noninfected women. The HIV-IgA immunoblot assays were performed at birth to 1 month, 3 months, and 6 months of age and compared with the Centers for Disease Control's classification system of HIV infection in the children. Children were followed up for at least 15 months to ensure accuracy of infection status. Setting. - Municipal hospital in central Brooklyn, NY, where the prevalence of HIV infection is high. Patients. - Serum samples from 58 children, 22 with documented HIV infection, 18 noninfected children born to seropositive women, and 18 children born to noninfected women, were studied. Main Outcome Measure. - Diagnosis of HIV infection using the Centers for Disease Control's classification scheme was compared with diagnosis using the HIV-IgA immunoblot assay for children 6 months of age or younger. Results. - The HIV-IgA immunoblot assay yielded negative results at 3 and 6 months of age for all 18 infants born to seronegative women; for the 18 seroreverting, noninfected children born to infected women, the assay yielded negative results at 1 month, 3 months, and 6 months of age. The positive predictive value of the assay was 100%-no false-positive results were identified in the 88 serum samples obtained from noninfected infants. For the HIV-infected children, sensitivity was a function of age: one (5.9%) of 17 infants had an assay that yielded positive results at birth to 1 month of age, 13 (62%) of 21 infants had assays that yielded positive results at 3 months of age, and 17 (77%) of 22 infants had assays that yielded positive results at 6 months of age. The presence or absence of symptoms did not affect the sensitivity. Conclusion. - The HIV-IgA immunoblot assay can detect a significant proportion of infected children during an early asymptomatic period of their life. This relatively inexpensive, easily standardized assay may allow for institution of therapy before the onset of clinical symptoms. C1 NIAID,DIV AIDS,BETHESDA,MD 20892. SUNY HLTH SCI CTR,DEPT OBSTET & GYNECOL,BROOKLYN,NY. THEOBALD SMITH RES INST,BOSTON,MA. NICHHD,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,BETHESDA,MD 20892. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT PEDIAT,BRONX,NY 10461. NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. SUNY HLTH SCI CTR,DEPT PEDIAT,BROOKLYN,NY. RP LANDESMAN, S (reprint author), SUNY HLTH SCI CTR,DEPT MED,DIV INFECT DIS,450 CLARKSON AVE,BOX 122,BROOKLYN,NY 11203, USA. FU NICHD NIH HHS [N0-1-HD-8-2913, R0-HD-25714-01, N0-1-HD-8-2917] NR 25 TC 63 Z9 63 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 25 PY 1991 VL 266 IS 24 BP 3443 EP 3446 DI 10.1001/jama.266.24.3443 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA GV878 UT WOS:A1991GV87800029 PM 1744958 ER PT J AU PARK, DJ MIN, HK RHEE, SG AF PARK, DJ MIN, HK RHEE, SG TI IGE-INDUCED TYROSINE PHOSPHORYLATION OF PHOSPHOLIPASE C-GAMMA-1 IN RAT BASOPHILIC LEUKEMIA-CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID MEDIATED SIGNAL TRANSDUCTION; MAST-CELLS; HISTAMINE-RELEASE; IMMUNOGLOBULIN-E; PERTUSSIS TOXIN; C-GAMMA; HIGH-AFFINITY; 2H3 CELLS; RECEPTOR; SECRETION AB Stimulation of rat basophilic leukemia (RBL-2H3) cells with oligomeric IgE elicited a rapid and transient phosphorylation of phospholipase C (PLC)-gamma-1 on tyrosine residues. Prior incubation of RBL-2H3 cells with a protein tyrosine kinase inhibitor, herbimycin A, prevented the tyrosine phosphorylation of PLC-gamma-1 as well as the hydrolysis of phosphatidylinositol 4,5-bisphosphate induced by oligomeric IgE. However, 5'-(N-ethyl)carboxamidoadenosine, which is known to activate PLC through a G protein, did not elicit tyrosine phosphorylation of PLC-gamma-1. These results, together with previous findings showing that tyrosine phosphorylation of PLC-gamma-1 enhances its catalytic activity, indicate that phosphorylation of PLC-gamma-1 by a nonreceptor tyrosine kinase is the mechanism by which IgE receptor aggregation triggers PLC activation. C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. RI Park, Do-Joon/J-2736-2012 NR 37 TC 189 Z9 190 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 DEC 25 PY 1991 VL 266 IS 36 BP 24237 EP 24240 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GW845 UT WOS:A1991GW84500002 PM 1662204 ER PT J AU SHARMA, VS BANDYOPADHYAY, D BERJIS, M RIFKIND, J BOSS, GR AF SHARMA, VS BANDYOPADHYAY, D BERJIS, M RIFKIND, J BOSS, GR TI DOUBLE-MIXING KINETIC-STUDIES OF THE REACTIONS OF MONOLIGANDED SPECIES OF HEMOGLOBIN - ALPHA-2(CO)1-BETA-2 AND ALPHA-2-BETA-2(CO)1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CARBON-MONOXIDE; LIGAND-BINDING; CARBOXYHEMOGLOBIN AB The kinetics of CO association to and dissociation from the two isomers of monoliganded species alpha(I)CO-beta(I)(alpha(II)beta(II)) and alpha(I)beta(I)(alpha(II)beta(II)CO) has been studied by double-mixing stopped-flow and microperoxidase methods. The monoliganded species were generated by hybridization between excess ferric Hb and alpha-2CO-beta-2+ or alpha-2+-beta-2CO prepared by high-pressure liquid chromatography (HPLC). The results indicated that: 1) there were no significant differences in the reactivities of alpha and beta-chains in the first step of ligation; 2) in the second step of ligation there was significant cooperativity in the reaction of deoxyhemoglobin with 0.05 or 0.1 equivalent of CO. Diliganded species were therefore formed in significant amounts. The double-mixing HPLC results suggested that in the second step of ligation alpha-chains reacted faster than the beta chains, and the main diliganded species formed was alpha(I)beta(I)CO(alpha(II)CO-beta(II)) or its isomer alpha(I)CO(I)(alpha(II)beta(II)CO). These results seem to indicate that the reaction of the first CO is mostly random and in the second step of ligation CO binds more to the tetramers in which one beta-chain is already ligated: alpha(I)beta(I)(alpha(II)beta(II)) + CO --> alpha(I)CO-beta(I)(alpha(II)beta(II) and alpha(I)beta(I)CO(alpha(II)beta(II)) + CO --> alpha(I)beta(I)CO(alpha(II)CO-beta(II). C1 NIH,GERONTOL RES UNIT,BETHESDA,MD 20892. RP SHARMA, VS (reprint author), UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093, USA. FU NHLBI NIH HHS [HL31159] NR 20 TC 11 Z9 11 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 DEC 25 PY 1991 VL 266 IS 36 BP 24492 EP 24497 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GW845 UT WOS:A1991GW84500040 PM 1761549 ER PT J AU STRAKA, JG BLOOMER, JR KEMPNER, ES AF STRAKA, JG BLOOMER, JR KEMPNER, ES TI THE FUNCTIONAL SIZE OF FERROCHELATASE DETERMINED INSITU BY RADIATION INACTIVATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BOVINE PROTOPORPHYRIA; LIVER-FERROCHELATASE; MOUSE FERROCHELATASE; BICINCHONINIC ACID; MOLECULAR-CLONING; TARGET ANALYSIS; PURIFICATION; HEME; GLUCOSE-6-PHOSPHATE-DEHYDROGENASE; EXPRESSION AB Ferrochelatase (EC 4.99.1.1) catalyzes the final step of heme biosynthesis, the insertion of iron(II) into protoporphyrin. It is an integral protein of the inner mitochondrial membrane. The functional size of bovine hepatic ferrochelatase has been studied in situ using radiation inactivation analysis. The functional unit required for enzymic activity in intact mitochondria was found to have a mass of 82 +/- 13 kDa. In contrast, the structural unit (evaluated in immunoblots following sodium dodecyl sulfate-polyacrylamide gel electrophoresis) has a mass of 40 +/- 10 kDa. Similar results were obtained when irradiation was performed on sodium cholate-solubilized mitochondria. The presence or absence of dithiothreitol during irradiation had no effect on target sizes obtained from either intact or solubilized mitochondria. Pairwise comparison of the functional and structural target sizes from each set of irradiated samples yielded a ratio of 2.0 +/- 0.4. Previous studies using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration chromatography have shown that a M(r) 40,000 peptide is associated with ferrochelatase activity. This study shows that the functional size of bovine ferrochelatase is approximately 80 kDa; the data are most consistent with a model for active ferrochelatase composed of two structural subunits of about 40 kDa each. C1 NIAMSD, PHYS BIOL LAB, BETHESDA, MD 20892 USA. RP STRAKA, JG (reprint author), UNIV MINNESOTA, SCH MED, DEPT MED, DIGHT LABS, 400 CHURCH ST SE, MINNEAPOLIS, MN 55455 USA. FU NIDDK NIH HHS [DK-26466] NR 32 TC 39 Z9 39 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 DEC 25 PY 1991 VL 266 IS 36 BP 24637 EP 24641 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GW845 UT WOS:A1991GW84500062 PM 1761561 ER PT J AU ZHANG, L LEVY, A RIFKIND, JM AF ZHANG, L LEVY, A RIFKIND, JM TI AUTOXIDATION OF HEMOGLOBIN ENHANCED BY DISSOCIATION INTO DIMERS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LIGAND-BINDING; BIS(3,5-DIBROMOSALICYL) FUMARATE; NUCLEOPHILIC DISPLACEMENT; QUATERNARY ENHANCEMENT; SUBUNIT DISSOCIATION; DISTAL HISTIDINE; OXYGEN BINDING; ALPHA-CHAINS; MECHANISM; SUPEROXIDE AB Autoxidation as a function of hemoglobin concentration indicates a 17-fold increase in the rate of autoxidation from 0.25 (%/h) to 4.3 (%/h) when tetrameric oxyhemoglobin dissociates into dimers. As a result of this large enhancement, a contribution of dissociation to the autoxidation is evident even at relatively high concentrations of hemoglobin for which it is usually considered that dissociation can be neglected. The mechanism for this phenomenon is attributed to alterations in the ligand pocket which occur when constraints due to subunit contacts within the R-state are eliminated. RP ZHANG, L (reprint author), NIA,GERONTOL RES CTR,CELLULAR & MOLEC BIOL LAB,BALTIMORE,MD 21224, USA. NR 38 TC 57 Z9 57 U1 1 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 DEC 25 PY 1991 VL 266 IS 36 BP 24698 EP 24701 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GW845 UT WOS:A1991GW84500071 PM 1761565 ER PT J AU BALLA, T SIM, SS IIDA, T CHOI, KY CATT, KJ RHEE, SG AF BALLA, T SIM, SS IIDA, T CHOI, KY CATT, KJ RHEE, SG TI AGONIST-INDUCED CALCIUM SIGNALING IS IMPAIRED IN FIBROBLASTS OVERPRODUCING INOSITOL 1,3,4,5-TETRAKISPHOSPHATE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RAT-LIVER CELLS; 1,4,5-TRISPHOSPHATE 3-KINASE; INTRACELLULAR CA-2+; BINDING-SITES; TETRAKISPHOSPHATE; RELEASE; BRAIN; TRISPHOSPHATE; PURIFICATION; KINASE AB The proposed Ca2+-signaling actions of inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4), formed by phosphorylation of the primary Ca2+-mobilizing messenger, inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), were analyzed in NIH 3T3 and CCL39 fibroblasts transfected with rat brain Ins(1,4,5)P3 3-kinase. In such kinase-transfected cells, the conversion of Ins(1,4,5)P3 to Ins(1,3,4,5)P4 during agonist stimulation was greatly increased, with a concomitant reduction in Ins(1,4,5)P3 levels and attenuation of both the cytoplasmic Ca2+ increase and the Ca2+ influx response. This reduction in Ca2+ signaling was observed during activation of receptors coupled to guanine nucleotide-binding proteins (thrombin and bradykinin), as well as with those possessing tyrosine kinase activity. Single-cell Ca2+ measurements in CCL39 cells revealed that the smaller averaged Ca2+ response of enzyme-transfected cells was due to a marked increase in the number of cells expressing small and slow Ca2+ increases, in contrast to the predominantly large and rapid Ca2+ responses of vector-transfected controls. There was no evidence that high Ins(1,3,4,5)P4 levels promote Ca2+ mobilization, Ca2+ entry, or Ca2+ sequestration. These data indicate that Ins(1,4,5)P3 is the major determinant of the agonist-induced Ca2+ signal in fibroblasts and that Ins(1,3,4,5)P4 does not appear to contribute significantly to this process. Instead, Ins(1,4,5)3 3-kinase may serve as a negative regulator of the Ca2+-phosphoinositide signal transduction mechanism. C1 NHLBI,BIOCHIM & GENET MICROBIENNE LAB,BETHESDA,MD 20892. RP BALLA, T (reprint author), NICHHD,ENDOCRINOL & REPROD RES BRANCH,BLDG 10,RM B1-L-400,BETHESDA,MD 20892, USA. OI Balla, Tamas/0000-0002-9077-3335 NR 42 TC 36 Z9 36 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 DEC 25 PY 1991 VL 266 IS 36 BP 24719 EP 24726 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GW845 UT WOS:A1991GW84500074 PM 1662215 ER PT J AU HORTON, WE BALAKIR, R PRECHT, P LIANG, CT AF HORTON, WE BALAKIR, R PRECHT, P LIANG, CT TI 1,25-DIHYDROXYVITAMIN-D3 DOWN-REGULATES AGGRECAN PROTEOGLYCAN EXPRESSION IN IMMORTALIZED RAT CHONDROCYTES THROUGH A POSTTRANSCRIPTIONAL MECHANISM SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VITAMIN-D; CELLS; CARTILAGE; CULTURE; INVITRO; PROTEIN; 24R,25-DIHYDROXYCHOLECALCIFEROL; 1,25-DIHYDROXYCHOLECALCIFEROL; SEQUENCE; GENES AB We have examined the effects of various analogs of vitamin D on the expression of the aggrecan proteoglycan by an immortalized rat chondrocyte cell line. The active metabolite of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), produced a concentration-dependent reduction in the synthesis of aggrecan as monitored by histochemical staining of the matrix, incorporation of [S-35]sulfate, and the level of aggrecan core protein. Other analogs of vitamin D were much less potent or had no activity whatsoever. The reduced expression of aggrecan was caused by a dramatic decrease in the steady-state level of the mRNA coding for the aggrecan core protein. A nuclear run-off analysis revealed that the rate of transcription of the aggrecan gene was not significantly altered by 1,25(OH)2D3 treatment, suggesting that the metabolite was acting through a post-transcriptional mechanism. Experiments using the transcriptional inhibitor actinomycin D also supported a nondirect effect of 1,25(OH)2D3 on the expression of the aggrecan gene. These results suggest that the vitamin D metabolite activates a new pattern of gene expression which results in a more rapid turnover of the aggrecan mRNA. This system should be useful for characterizing the regulation of chondrocyte gene expression by vitamin D. RP HORTON, WE (reprint author), NIA,GERONTOL RES CTR,BALTIMORE,MD 21224, USA. NR 25 TC 16 Z9 16 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 DEC 25 PY 1991 VL 266 IS 36 BP 24804 EP 24808 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GW845 UT WOS:A1991GW84500085 PM 1761574 ER PT J AU PERRYMAN, S NISHIO, J CHESEBRO, B AF PERRYMAN, S NISHIO, J CHESEBRO, B TI COMPLETE NUCLEOTIDE-SEQUENCE OF FRIEND MURINE LEUKEMIA-VIRUS, STRAIN FB29 SO NUCLEIC ACIDS RESEARCH LA English DT Note ID ENVELOPE GENE RP PERRYMAN, S (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840, USA. NR 8 TC 35 Z9 38 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 DEC 25 PY 1991 VL 19 IS 24 BP 6950 EP 6950 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GX701 UT WOS:A1991GX70100039 PM 1762923 ER PT J AU FUTREAL, PA BARRETT, JC WISEMAN, RW AF FUTREAL, PA BARRETT, JC WISEMAN, RW TI AN ALU POLYMORPHISM INTRAGENIC TO THE TP53 GENE SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 UNIV N CAROLINA,DEPT PATHOL,CHAPEL HILL,NC 27599. RP FUTREAL, PA (reprint author), NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709, USA. NR 4 TC 120 Z9 122 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC 25 PY 1991 VL 19 IS 24 BP 6977 EP 6977 DI 10.1093/nar/19.24.6977 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GX701 UT WOS:A1991GX70100077 PM 1762941 ER PT J AU THOMAS, DC ROBERTS, JD SABATINO, RD MYERS, TW TAN, CK DOWNEY, KM SO, AG BAMBARA, RA KUNKEL, TA AF THOMAS, DC ROBERTS, JD SABATINO, RD MYERS, TW TAN, CK DOWNEY, KM SO, AG BAMBARA, RA KUNKEL, TA TI FIDELITY OF MAMMALIAN DNA-REPLICATION AND REPLICATIVE DNA-POLYMERASES SO BIOCHEMISTRY LA English DT Article ID LAGGING STRAND SYNTHESIS; 5' EXONUCLEASE ACTIVITY; INVITRO REQUIRES PCNA; SIMIAN VIRUS-40; CALF THYMUS; IMMUNOAFFINITY CHROMATOGRAPHY; SACCHAROMYCES-CEREVISIAE; DROSOPHILA-MELANOGASTER; MUTATIONAL SPECIFICITY; REVERSE-TRANSCRIPTASE AB Current models suggest that two or more DNA polymerases may be required for high-fidelity semiconservative DNA replication in eukaryotic cells. In the present study, we directly compare the fidelity of SV40 origin-dependent DNA replication in human cell extracts to the fidelity of mammalian DNA polymerases alpha, delta, and epsilon using lacZ-alpha of M13mp2 as a reporter gene. Their fidelity, in decreasing order, is replication greater-than-or-equal-to pol-epsilon > pol-delta > pol-alpha. DNA sequence analysis of mutants derived from extract reactions suggests that replication is accurate when considering single-base substitutions, single-base frameshifts, and larger deletions. The exonuclease-containing calf thymus DNA polymerase-epsilon is also highly accurate. When high concentrations of deoxynucleoside triphosphates and deoxyguanosine monophosphate are included in the pol-epsilon reaction, both base substitution and frameshift error rates increase. This response suggests that exonucleolytic proofreading contributes to the high base substitution and frameshift fidelity. Exonuclease-containing calf thymus DNA polymerase-delta, which requires proliferating cell nuclear antigen for efficient synthesis, is significantly less accurate than pol-epsilon. In contrast to pol-epsilon , pol-delta generates errors during synthesis at a relatively modest concentration of deoxynucleoside triphosphates (100-mu-M), and the error rate did not increase upon addition of adenosine monophosphate. Thus, we are as yet unable to demonstrate that exonucleolytic proofreading contributes to accuracy during synthesis by DNA polymerase-delta. The four-subunit DNA polymerase alpha-primase complex from both HeLa cells and calf thymus is the least accurate replicative polymerase. Fidelity is similar whether the enzyme is assayed immediately after purification or after being stored frozen. DNA sequence analysis of independent mutants generated by each enzyme shows that they all produce single-base substitution and frameshift errors, as well as larger deletions. However, the three polymerases have distinctly different error rates and error specificities, which has implications for their roles in the various stages of DNA replication. C1 NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. UNIV ROCHESTER,DEPT BIOCHEM & MICROBIOL,ROCHESTER,NY 14642. UNIV ROCHESTER,CTR CANC,ROCHESTER,NY 14642. UNIV MIAMI,DEPT MED,MIAMI,FL 33101. UNIV MIAMI,DEPT BIOCHEM MOLEC BIOL,MIAMI,FL 33101. FU NIDDK NIH HHS [DK26206]; NIGMS NIH HHS [GM 24441] NR 74 TC 95 Z9 95 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 DEC 24 PY 1991 VL 30 IS 51 BP 11751 EP 11759 DI 10.1021/bi00115a003 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GW847 UT WOS:A1991GW84700003 PM 1751492 ER PT J AU HANCHARD, B LAGRENADE, L CARBERRY, C FLETCHER, V WILLIAMS, E CRANSTON, B BLATTNER, WA MANNS, A AF HANCHARD, B LAGRENADE, L CARBERRY, C FLETCHER, V WILLIAMS, E CRANSTON, B BLATTNER, WA MANNS, A TI CHILDHOOD INFECTIVE DERMATITIS EVOLVING INTO ADULT T-CELL LEUKEMIA AFTER 17 YEARS SO LANCET LA English DT Letter C1 NIH,VIRAL EPIDEMIOL SECT,BETHESDA,MD 20892. RP HANCHARD, B (reprint author), UNIV W INDIES,KINGSTON 7,JAMAICA. FU NCI NIH HHS [N01-CP-31006] NR 9 TC 55 Z9 59 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 DEC 21 PY 1991 VL 338 IS 8782-3 BP 1593 EP 1594 DI 10.1016/0140-6736(91)92413-V PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA GW036 UT WOS:A1991GW03600034 PM 1683991 ER PT J AU AARONSON, SA BOTTARO, DP MIKI, T RON, D FINCH, PW FLEMING, TP AHN, J TAYLOR, WG RUBIN, JS AF AARONSON, SA BOTTARO, DP MIKI, T RON, D FINCH, PW FLEMING, TP AHN, J TAYLOR, WG RUBIN, JS TI KERATINOCYTE GROWTH-FACTOR - A FIBROBLAST GROWTH-FACTOR FAMILY MEMBER WITH UNUSUAL TARGET-CELL SPECIFICITY SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID PROTEIN-TYROSINE KINASE; FACTOR RECEPTOR GENES; SIMIAN SARCOMA-VIRUS; MAMMARY-TUMOR VIRUS; MESSENGER-RNA; AFFINITY-CHROMATOGRAPHY; NUCLEOTIDE-SEQUENCE; HEPARIN AFFINITY; CODING SEQUENCE; BOVINE BRAIN C1 TECHNION ISRAEL INST TECHNOL,FAC BIOL,IL-32000 HAIFA,ISRAEL. RHODE ISL HOSP,DEPT NEUROSURG,PROVIDENCE,RI 02903. RP AARONSON, SA (reprint author), NCI,CELLULAR & MOLEC BIOL LAB,BLDG 37,ROOM IE24,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 63 TC 139 Z9 145 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD DEC 20 PY 1991 VL 638 BP 62 EP 77 DI 10.1111/j.1749-6632.1991.tb49018.x PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM209 UT WOS:A1991JM20900009 PM 1664700 ER PT J AU HALABAN, R FUNASAKA, Y LEE, P RUBIN, J RON, D BIRNBAUM, D AF HALABAN, R FUNASAKA, Y LEE, P RUBIN, J RON, D BIRNBAUM, D TI FIBROBLAST GROWTH-FACTORS IN NORMAL AND MALIGNANT MELANOCYTES SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID STEM-CELL FACTOR; TYROSINE KINASE-ACTIVITY; PHOSPHOLIPASE-C-GAMMA; FACTOR RECEPTOR; BASIC-FGF; MOLECULAR-CLONING; NUCLEOTIDE-SEQUENCE; TRANSFORMING GENE; KIT PROTOONCOGENE; HUMAN-MELANOMA C1 SCRIPPS RES INST, DEPT MOLEC & EXPTL MED, LA JOLLA, CA 92037 USA. NCI, CELLULAR & MOLEC BIOL LAB, BETHESDA, MD 20892 USA. TECHNION ISRAEL INST TECHNOL, DEPT BIOL, IL-32000 HAIFA, ISRAEL. INST J PAOLI I CALMETTES, INSERM, U119, F-13009 MARSEILLE, FRANCE. RP HALABAN, R (reprint author), YALE UNIV, SCH MED, DEPT DERMATOL, 500 LCI, POB 333, NEW HAVEN, CT 06510 USA. FU NCI NIH HHS [1 RO1 CA 04679, 5 R29 CA44542]; NIAMS NIH HHS [5 PO1 AR25252] NR 76 TC 46 Z9 46 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD DEC 20 PY 1991 VL 638 BP 232 EP 243 DI 10.1111/j.1749-6632.1991.tb49034.x PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM209 UT WOS:A1991JM20900025 PM 1723854 ER PT J AU BAIRD, A KLAGSBRUN, M AARONSON, S ABRAHAM, J BASILICO, C BIRNBAUM, D BOHLEN, P BURGESS, W DICKSON, C FIDDES, J GOLDFARB, M MACIAG, T MARTIN, G PETERS, G RUBIN, J THOMAS, K TERADA, M YOSHIDA, T AF BAIRD, A KLAGSBRUN, M AARONSON, S ABRAHAM, J BASILICO, C BIRNBAUM, D BOHLEN, P BURGESS, W DICKSON, C FIDDES, J GOLDFARB, M MACIAG, T MARTIN, G PETERS, G RUBIN, J THOMAS, K TERADA, M YOSHIDA, T TI NOMENCLATURE MEETING REPORT AND RECOMMENDATIONS JANUARY 17, 1991 SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID FIBROBLAST GROWTH-FACTOR; TRANSFORMING GENE; K-FGF; ONCOGENE; SEQUENCE; HST; INT-2; MAPS; FAMILY; CODONS C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT BIOL CHEM,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT SURG,BOSTON,MA 02115. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. CALIF BIOTECHNOL INC,MT VIEW,CA 94043. INSERM,U119,F-13009 MARSEILLE,FRANCE. AMER CYANAMID CO,DIV MED RES,PEARL RIVER,NY 10965. AMER REV CROSS,JEROME H HOLLAND LAB BIOMED SCI,MOLEC BIOL LAB,ROCKVILLE,MD 20855. IMPERIAL CANC RES FUND,VIRAL CARCINOGENESIS LAB,LONDON WC2A 3PX,ENGLAND. COLUMBIA UNIV COLL PHYS & SURG,DEPT BIOCHEM & MOLEC BIOPHYS,NEW YORK,NY 10032. NATL CANC CTR,RES INST,DIV GENET,CHUO KU,TOKYO 104,JAPAN. MERCK RES LABS,DEPT BIOCHEM,RAHWAY,NJ 07065. RP BAIRD, A (reprint author), WHITTIER INST DIABET & ENDOCRINOL,DEPT MOLEC & CELLULAR BIOL,9894 GENESEE AVE,LA JOLLA,CA 92037, USA. NR 26 TC 24 Z9 24 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD DEC 20 PY 1991 VL 638 BP R13 EP R16 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM209 UT WOS:A1991JM20900002 ER PT J AU JOHNSON, AE HARBAUGH, CR GELHARD, RE AF JOHNSON, AE HARBAUGH, CR GELHARD, RE TI PROJECTIONS FROM THE VENTROMEDIAL NUCLEUS OF THE HYPOTHALAMUS CONTAIN OXYTOCIN BINDING-SITES SO BRAIN RESEARCH LA English DT Note DE OXYTOCIN RECEPTOR; ESTRADIOL; VENTROMEDIAL HYPOTHALAMUS; VENTROMEDIAL HYPOTHALAMIC NUCLEUS; ELECTROLYTIC LESION; I-125-D(CH2)5[TYR(ME)2,THR4,TYR-NH2(9)]OVT; RECEPTOR AUTORADIOGRAPHY ID RECEPTOR-BINDING; TIME COURSE; RAT-BRAIN; STEROIDS; PROGESTERONE; DENSITY AB Experiments were conducted to determine the source of steroid-dependent oxytocin (OT) receptors that surround the ventrolateral portion of the ventromedial hypothalamic nucleus (vl-VMN). Ovariectomized rats received sham or unilateral electrolytic lesions of the vl-VMN. Three days later and for the next 4 days, animals were injected with 10-mu-g of estradiol benzoate (EB). OT receptors were labelled with I-125-d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]OVT and binding was assessed with autoradiographic methods. Lesions of the vl-VMN reduced OT receptor binding in the area surrounding the nucleus by over 80% indicating that the majority of OT receptors in the ventromedial hypothalamus are located on fibers originating within the VMN. C1 KAROLINSKA INST,HUDDINGE HOSP,CLIN RES CTR,DIV MED CELL & NEUROBIOL,S-14104 HUDDINGE,SWEDEN. NIMH,CLIN SCI LAB,COMPARAT STUDIES BRAIN BEHAV SECT,POOLESVILLE,MD 20837. NR 23 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD DEC 20 PY 1991 VL 567 IS 2 BP 332 EP 336 DI 10.1016/0006-8993(91)90815-D PG 5 WC Neurosciences SC Neurosciences & Neurology GA GY128 UT WOS:A1991GY12800022 PM 1667903 ER PT J AU NASH, HA GRANSTON, AE AF NASH, HA GRANSTON, AE TI SIMILARITY BETWEEN THE DNA-BINDING DOMAINS OF IHF PROTEIN AND TFIID PROTEIN SO CELL LA English DT Letter ID INTEGRATION HOST FACTOR; YEAST; SEQUENCES; MUTANTS; SITES RP NASH, HA (reprint author), NIMH,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 19 TC 27 Z9 27 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD DEC 20 PY 1991 VL 67 IS 6 BP 1037 EP 1038 DI 10.1016/0092-8674(91)90280-C PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GX164 UT WOS:A1991GX16400003 PM 1760837 ER PT J AU ENGELMAN, A MIZUUCHI, K CRAIGIE, R AF ENGELMAN, A MIZUUCHI, K CRAIGIE, R TI HIV-1 DNA INTEGRATION - MECHANISM OF VIRAL-DNA CLEAVAGE AND DNA STRAND TRANSFER SO CELL LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CYCLIC DIGUANYLIC ACID; RETROVIRAL DNA; ACETOBACTER-XYLINUM; CELLULOSE SYNTHESIS; CHEMICAL SYNTHESIS; PROTEIN; INVITRO; RECOMBINATION; SEQUENCES AB Retroviral DNA integration involves a coordinated set of DNA cutting and joining reactions. Linear viral DNA is cleaved at each 3' end to generate the precursor ends for integration. The resulting recessed 3' ends are inserted into target DNA by a subsequent DNA strand transfer reaction. Purified HIV-1 integration protein carries out both of these steps in vitro. Two novel forms of the dinucleotide cleaved from HIV-1 DNA were identified and one, a cyclic dinucleotide, was used to analyze the stereochemical course of viral DNA cleavage. Both viral DNA cleavage and DNA strand transfer display inversion at chiral phosphorothioates during the course of the reaction. These results suggest that both reactions occur by a one-step mechanism without involvement of a covalent protein-DNA intermediate. RP ENGELMAN, A (reprint author), NIDDKD, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. NR 43 TC 496 Z9 509 U1 3 U2 29 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD DEC 20 PY 1991 VL 67 IS 6 BP 1211 EP 1221 DI 10.1016/0092-8674(91)90297-C PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GX164 UT WOS:A1991GX16400019 PM 1760846 ER PT J AU POMMIER, Y CAPRANICO, G ORR, A KOHN, KW AF POMMIER, Y CAPRANICO, G ORR, A KOHN, KW TI DISTRIBUTION OF TOPOISOMERASE-II CLEAVAGE SITES IN SIMIAN VIRUS-40 DNA AND THE EFFECTS OF DRUGS SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE TOPOISOMERASE-II; SIMIAN VIRUS-40; REPLICATION; ENHANCERS; TOPOISOMERASE INHIBITORS ID CHROMOSOME CONDENSATION; SACCHAROMYCES-CEREVISIAE; DROSOPHILA-MELANOGASTER; REPLICATION FORKS; ANTITUMOR DRUGS; SV40 DNA; CHROMATIN; IDENTIFICATION; TRANSCRIPTION; SEPARATION RP POMMIER, Y (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892, USA. RI Capranico, Giovanni/K-1678-2014 OI Capranico, Giovanni/0000-0002-8708-6454 NR 50 TC 66 Z9 66 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD DEC 20 PY 1991 VL 222 IS 4 BP 909 EP 924 DI 10.1016/0022-2836(91)90585-T PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GX790 UT WOS:A1991GX79000013 PM 1662289 ER PT J AU DALEMANS, W BARBRY, P CHAMPIGNY, G JALLAT, S DOTT, K DREYER, D CRYSTAL, RG PAVIRANI, A LECOCQ, JP LAZDUNSKI, M AF DALEMANS, W BARBRY, P CHAMPIGNY, G JALLAT, S DOTT, K DREYER, D CRYSTAL, RG PAVIRANI, A LECOCQ, JP LAZDUNSKI, M TI ALTERED CHLORIDE-ION CHANNEL KINETICS ASSOCIATED WITH THE DELTA-F508 CYSTIC-FIBROSIS MUTATION SO NATURE LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; EPITHELIAL-CELLS; EXPRESSION; GENE; CL; IDENTIFICATION; TRANSPORT; MEMBRANE AB CYSTIC fibrosis is associated with a defect in epithelial chloride ion transport (reviewed in refs 1, 2) which is caused by mutations in a membrane protein called CFTR (cystic fibrosis transmembrane conductance regulator) 3. Heterologous expression of CFTR produces cyclicAMP-sensitive Cl--channel activity 4-7. Deletion of phenylalanine at amino-acid position 508 in CFTR (DELTA-F508 CFTR) is the most common mutation in cystic fibrosis 8. It has been proposed that this mutation prevents glycoprotein maturation and its transport to its normal cellular location 9. We have expressed both CFIR and DELTA-F508 CFTR in Vero cells using recombinant vaccinia virus. Although far less DELTA-F508 CFTR reached the plasma membrane than normal CFTR, sufficient DELTA-F508 CFTR was expressed at the plasma membrane to permit functional analysis. DELTA-F508 CFIR expression induced a reduced activity of the cAMP-activated Cl- channel, with conductance, anion selectivity and open-time kinetics similar to those of CFIR, but with much greater closed times, resulting in a large decrease of open probability. The DELTA-F508 mutation thus seems to have two major consequences, an abnormal translocation of the CFTR protein which limits membrane insertion, and an abnormal function in mediating Cl- transport. C1 INST PHARMACOL MOLEC & CELLULAIRE,660 ROUTE LUCIOLES,SOPHIA ANTIPOLIS,F-06560 VALBONNE,FRANCE. TRANSGENE SA,F-67082 STRASBOURG,FRANCE. NHLBI,PULM BRANCH,BETHESDA,MD 20892. RI Barbry, Pascal/O-5021-2016 OI Barbry, Pascal/0000-0001-9632-6483 NR 23 TC 480 Z9 486 U1 3 U2 27 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD DEC 19 PY 1991 VL 354 IS 6354 BP 526 EP 528 DI 10.1038/354526a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GW751 UT WOS:A1991GW75100015 PM 1722027 ER PT J AU TABOR, E AF TABOR, E TI SIDS AND SUFFOCATION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP TABOR, E (reprint author), NCI,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 19 PY 1991 VL 325 IS 25 BP 1806 EP 1807 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA GV739 UT WOS:A1991GV73900013 ER PT J AU BARTON, NW BRADY, RO MURRAY, GJ ARGOFF, CE GREWAL, RP YU, KT DAMBROSIA, JM DIBISCEGLIE, AM HILL, SC PARKER, RI DOPPELT, SH MANKIN, HJ AF BARTON, NW BRADY, RO MURRAY, GJ ARGOFF, CE GREWAL, RP YU, KT DAMBROSIA, JM DIBISCEGLIE, AM HILL, SC PARKER, RI DOPPELT, SH MANKIN, HJ TI ENZYME-REPLACEMENT THERAPY FOR GAUCHERS-DISEASE - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID GLUCOCEREBROSIDASE C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP BARTON, NW (reprint author), NIH,BETHESDA,MD 20892, USA. NR 3 TC 18 Z9 18 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 DEC 19 PY 1991 VL 325 IS 25 BP 1811 EP 1811 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GV739 UT WOS:A1991GV73900022 ER PT J AU ROSSOUW, JE CANNER, PL HULLEY, SB AF ROSSOUW, JE CANNER, PL HULLEY, SB TI DEATHS FROM INJURY, VIOLENCE, AND SUICIDE IN SECONDARY PREVENTION TRIALS OF CHOLESTEROL LOWERING SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID MORTALITY C1 MARYLAND MED RES INST,BALTIMORE,MD 21210. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. RP ROSSOUW, JE (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 5 TC 24 Z9 24 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 DEC 19 PY 1991 VL 325 IS 25 BP 1813 EP 1813 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GV739 UT WOS:A1991GV73900027 PM 1834942 ER PT J AU ANDERSON, SE CALA, PM STEENBERGEN, C LONDON, RE MURPHY, E AF ANDERSON, SE CALA, PM STEENBERGEN, C LONDON, RE MURPHY, E TI EFFECTS OF HYPOXIA AND ACIDIFICATION ON MYOCARDIAL NA AND CA - ROLE OF NA-H AND NA-CA EXCHANGE SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article C1 DUKE UNIV,MED CTR,DEPT PATHOL,DURHAM,NC 27710. NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. RP ANDERSON, SE (reprint author), UNIV CALIF DAVIS,DEPT HUMAN PHYSIOL,DAVIS,CA 95616, USA. FU NHLBI NIH HHS [R01 HL039752] NR 5 TC 12 Z9 13 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD DEC 18 PY 1991 VL 639 BP 453 EP 455 DI 10.1111/j.1749-6632.1991.tb17332.x PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM210 UT WOS:A1991JM21000051 PM 1664705 ER PT J AU SONDIK, EJ AF SONDIK, EJ TI SMOKING-ATTRIBUTABLE CANCER MORTALITY SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter RP SONDIK, EJ (reprint author), NCI,DIV CANC PREVENT & CONTROL,BLDG 31,RM 10A49,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 18 PY 1991 VL 83 IS 24 BP 1834 EP 1834 DI 10.1093/jnci/83.24.1834 PG 1 WC Oncology SC Oncology GA GV162 UT WOS:A1991GV16200016 PM 1744927 ER PT J AU NIXON, RM RAUSCHER, FJ UPTON, AC DEVITA, VT BRODER, S RHOADS, JE PITOT, HC KORN, D CALABRESI, P SCHMIDT, BC LEDERBERG, J FREEMAN, HP KENNEDY, EM ROGERS, PG LASKER, M LETTON, AH AF NIXON, RM RAUSCHER, FJ UPTON, AC DEVITA, VT BRODER, S RHOADS, JE PITOT, HC KORN, D CALABRESI, P SCHMIDT, BC LEDERBERG, J FREEMAN, HP KENNEDY, EM ROGERS, PG LASKER, M LETTON, AH TI THE IMPACT OF THE NATIONAL CANCER ACT SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Discussion C1 NCI,BETHESDA,MD 20892. US HOUSE REPRESENTAT,SUBCOMM HLTH & ENVIRONM,WASHINGTON,DC 20515. AMER CANC SOC,NEW YORK,NY 10017. RP BRODER, S (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 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 DEC 18 PY 1991 VL 83 IS 24 BP S1 EP S16 PG 16 WC Oncology SC Oncology GA GV162 UT WOS:A1991GV16200010 ER PT J AU PAULY, GT HUGHES, SH MOSCHEL, RC AF PAULY, GT HUGHES, SH MOSCHEL, RC TI A SECTORED COLONY ASSAY FOR MONITORING MUTAGENESIS BY SPECIFIC CARCINOGEN DNA ADDUCTS IN ESCHERICHIA-COLI SO BIOCHEMISTRY LA English DT Article ID ALKYLATING-AGENTS; OGT GENE; SITE; REPAIR; INVIVO; OLIGODEOXYNUCLEOTIDES; O-6-METHYLGUANINE; GUANINE; ALKYLTRANSFERASE; O-6-ALKYLGUANINE AB To study the mutagenicity of various carcinogen-DNA adducts in Escherichia coli, a cassette plasmid was developed that permits positioning of specific carcinogen-modified bases within the ATG initiation codon of the lacZ' alpha-complementation gene. Adduct-induced mutations inactivate the gene and lead to formation of blue and white sectored colonies when transformants from an alpha-complementing version of E. coli strain AB1157 are grown on media containing 5-bromo-chloro-3-indolyl beta-D-galactoside. In the absence of mutation, blue colonies are produced. This system has been used to measure the mutagenicity of O6-methyl-, O6-ethyl-, and O6-benzyl-2'-deoxyguanosine residues incorporated in place of the normal 2'-deoxyguanosine of the ATG initiation codon. Although a low percentage of sectored colonies was produced in this repair-proficient strain, pretreatment of the bacteria with N-methyl-N'-nitro-N-nitrosoguanidine to disable DNA repair led to a dose-dependent increase in the percentage of sectored colonies. This percentage increased as a function of modified guanine in the order O6-benzyl- < O6-methyl- < O6-ethyl-2'-deoxyguanosine. The only mutations detected at the site of incorporation of these O6-substituted guanines were G-to-A transitions. This sectored colony assay system permits convenient screening of large numbers of colonies and simplifies quantification of modified-base-induced mutations whether they be single-base changes, frameshifts, insertions, or deletions. C1 NCI,FREDERICK CANC RES & DEV CTR,CHEM CARCINOGENESIS & MOLEC MECH CARCINOGENESIS LABS,FREDERICK,MD 21702. RP MOSCHEL, RC (reprint author), NCI,FREDERICK CANC RES & DEV CTR,CHEM CARCINOGENESIS & MOLEC MECH CARCINOGENESIS LABS,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101] NR 35 TC 15 Z9 15 U1 2 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 17 PY 1991 VL 30 IS 50 BP 11700 EP 11706 DI 10.1021/bi00114a014 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GV074 UT WOS:A1991GV07400014 PM 1751489 ER PT J AU BECERRA, SP KUMAR, A LEWIS, MS WIDEN, SG ABBOTTS, J KARAWYA, EM HUGHES, SH SHILOACH, J WILSON, SH AF BECERRA, SP KUMAR, A LEWIS, MS WIDEN, SG ABBOTTS, J KARAWYA, EM HUGHES, SH SHILOACH, J WILSON, SH TI PROTEIN PROTEIN INTERACTIONS OF HIV-1 REVERSE-TRANSCRIPTASE - IMPLICATION OF CENTRAL AND C-TERMINAL REGIONS IN SUBUNIT BINDING SO BIOCHEMISTRY LA English DT Article ID RNASE-H ACTIVITY; ESCHERICHIA-COLI; AIDS VIRUS; MONOCLONAL-ANTIBODIES; STRUCTURAL PROTEINS; GENE-PRODUCTS; HTLV-III/LAV; EXPRESSION; DOMAIN; MECHANISM AB Human immunodeficiency virus 1 reverse transcriptase (RT) purified from virions is composed of a approximately 51 000 M(r) polypeptide and a approximately 66 000 M(r) polypeptide that are thought to be in heterodimer structure (Chandra et al., 1986; Hansen et al., 1988; Starnes & Cheng, 1989) and are identical except for a 15 000 M(r) C-terminal truncation in the smaller species (Di Marzo-Veronese et al., 1986). We prepared individual bacterial-recombinant RTs as the approximately 66 000 M(r) polypeptide (p66) or as the approximately 51 000 M(r) polypeptide (p51) and then conducted various in vitro protein-protein binding experiments. Analytical ultracentrifugation studies in 0.25 M NaCl at pH 6.5 revealed that p66 was in monomer-dimer equilibrium with K(A) of 5.1 X 10(4) M-1. p51 failed to dimerize and behaved as a monomer under these conditions. Mixing of the p66 and p51 polypeptides resulted in a 1:1 heterodimer with K(A) of 4.9 x 10(5) M-1. These results on formation of the p66/p66 homodimer and p66/p51 heterodimer were confirmed by gel filtration analysis using FPLC Superose-12 columns. Binding between p66 and individual p66 segment polypeptides also was observed using an immunoprecipitation assay. Binding between p51 and p66 in this assay was resistant to the presence of approximately 1 M NaCl, suggesting that the binding free energy has a large hydrophobic component. C-Terminal truncation of p66 to yield a 29-kDa polypeptide eliminated binding to p66, and N-terminal truncation of p66 to yield a 15-kDa peptide also eliminated binding to p66. The results indicate that purified individual RT peptides p51 and p66 are capable of binding to form a 1:1 heterodimer and suggest that the central region of p66 is required for this subunit binding; the C-terminal region (15 000 M(r)) of p66 appears to be required also, as p51 alone did not dimerize. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,BRI BASIC RES PROGRAM,FREDERICK,MD 21701. NIDDKD,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892. RP WILSON, SH (reprint author), NCI,BIOCHEM LAB,BETHESDA,MD 20892, USA. NR 46 TC 73 Z9 74 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 17 PY 1991 VL 30 IS 50 BP 11707 EP 11719 DI 10.1021/bi00114a015 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GV074 UT WOS:A1991GV07400015 PM 1721535 ER PT J AU DACUNHA, A ALOYO, VJ VITKOVIC, L AF DACUNHA, A ALOYO, VJ VITKOVIC, L TI DEVELOPMENTAL REGULATION OF GAP-43, GLUTAMINE-SYNTHETASE AND BETA-ACTIN MESSENGER-RNA IN RAT CORTICAL ASTROCYTES SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Note DE ASTROCYTE; DEVELOPMENT; GAP-43; GLUTAMINE SYNTHETASE; ACTIN MESSENGER RNA ID PROTEIN GAP-43; NERVE GROWTH; BRAIN; EXPRESSION; CULTURES; TUBULIN; OLIGODENDROCYTES; LOCALIZATION; MEMBRANES AB Steady-state levels of mRNA encoding growth-associated protein 43 (GAP-43), glutamine synthetase (GS) and beta-actin were measured during development of neonatal rat cortical astrocytes in primary culture. GAP-43 mRNA and protein decreased rapidly during the first 2 weeks and slowly thereafter. In contrast, GS mRNA increased approximately 3-fold during the first 2 weeks and reached maximum by day 15. Actin mRNA first increased up to 8 days and decreased thereafter reaching a constant amount by 15 days, similar to the initial low value. Thus, GAP-43, GS and beta-actin mRNA levels are differentially regulated during development of astrocytes in primary culture. Because the patterns of expression of astrocytic markers GS and GFAP (shown previously) in vitro and in vivo are similar to each other, primary cultures of astrocytes may be an excellent system for investigating mechanisms of developmental regulation of these genes. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. MED COLL PENN,DEPT PHARMACOL,PHILADELPHIA,PA 19129. NR 26 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD DEC 17 PY 1991 VL 64 IS 1-2 BP 212 EP 215 DI 10.1016/0165-3806(91)90228-B PG 4 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA GX499 UT WOS:A1991GX49900026 ER PT J AU ZHANG, R TSAIMORRIS, CH KITAMURA, M BUCZKO, E DUFAU, ML AF ZHANG, R TSAIMORRIS, CH KITAMURA, M BUCZKO, E DUFAU, ML TI CHANGES IN BINDING-ACTIVITY OF LUTEINIZING-HORMONE RECEPTORS BY SITE DIRECTED MUTAGENESIS OF POTENTIAL GLYCOSYLATION SITES SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID GONADOTROPIN RECEPTOR; LUTROPIN RECEPTOR; PURIFICATION C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,MOLEC ENDOCRINOL SECT,BETHESDA,MD 20892. RP DUFAU, ML (reprint author), NICHHD,ENDOCRINOL & REPROD RES BRANCH,MOLEC ENDOCRINOL SECT,BETHESDA,MD 20892, USA. NR 17 TC 34 Z9 34 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 16 PY 1991 VL 181 IS 2 BP 804 EP 808 DI 10.1016/0006-291X(91)91261-A PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GV237 UT WOS:A1991GV23700045 PM 1755859 ER PT J AU ROBERTS, CS GERTZ, SD KLUES, HG CANNON, RO MARON, BJ MCINTOSH, CL ROBERTS, WC AF ROBERTS, CS GERTZ, SD KLUES, HG CANNON, RO MARON, BJ MCINTOSH, CL ROBERTS, WC TI APPEARANCE OF OR PERSISTENCE OF SEVERE MITRAL REGURGITATION WITHOUT LEFT-VENTRICULAR OUTFLOW OBSTRUCTION AFTER PARTIAL VENTRICULAR SEPTAL MYOTOMY-MYECTOMY IN HYPERTROPHIC CARDIOMYOPATHY SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article C1 NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. RP ROBERTS, CS (reprint author), NHLBI,SURG BRANCH,BETHESDA,MD 20892, USA. NR 3 TC 5 Z9 5 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 15 PY 1991 VL 68 IS 17 BP 1726 EP 1728 DI 10.1016/0002-9149(91)90341-H PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA GU998 UT WOS:A1991GU99800035 PM 1746483 ER PT J AU POE, GS MCLAUGHLIN, JK POWELLGRINER, E PARSONS, CR ROBINSON, K AF POE, GS MCLAUGHLIN, JK POWELLGRINER, E PARSONS, CR ROBINSON, K TI THE TIME INTERVAL BETWEEN DEATH AND NEXT-OF-KIN CONTACT AND ITS EFFECTS ON RESPONSE RATES AND DATA QUALITY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE DATA COLLECTION; EPIDEMIOLOGIC METHODS; RESPONSE RATES AB The relation of the interval of time between death and next-of-kin contact to outcome variables including response rates and data quality was examined in a nationally representative sample of 17,713 deaths of persons 25 years of age or older that occurred in the United States in 1986. For most of the outcome variables examined, the length of time had little effect, although there was a small decrease in the response rate and a small increase in the refusal rate for contact 40 or more weeks after death. The small decrease in the response rate and small increase in the refusal rate for the longest interval examined held for most decedent background characteristics examined (age, race, cause of death, and type of informant.) Authorizations to contact health care facilities signed by the respondents decreased slightly as the interval increased. The rate of returned mailed questionnaires passing quality and consistency edits increased slightly with time since death. Substantive responses (versus blanks, don't knows, etc.) decreased as time since death increased. Certain questions such as those on income and birth control pill use showed a decrease in response with time since death. Overall, the effects of longer time intervals between death and next-of-kin contact were less than expected on response rates and data quality, although our findings may reflect the high overall response rate, 90.5%, leaving little opportunity for significant areas of nonresponse. C1 NCI,DIV CANC ETIOL,BIOSTAT BRANCH,EXECUT L N,ROOM 415,BETHESDA,MD 20892. NATL CTR HLTH STAT,VITAL & HLTH STAT PROGRAM,HYATTSVILLE,MD 20782. NR 8 TC 6 Z9 6 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 DEC 15 PY 1991 VL 134 IS 12 BP 1454 EP 1462 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA HC444 UT WOS:A1991HC44400013 PM 1776620 ER PT J AU FREEDMAN, LS SCHATZKIN, A WAX, Y AF FREEDMAN, LS SCHATZKIN, A WAX, Y TI THE IMPACT OF DIETARY MEASUREMENT ERROR ON PLANNING SAMPLE-SIZE REQUIRED IN A COHORT STUDY - REPLY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter C1 HEBREW UNIV JERUSALEM,DEPT STAT,JERUSALEM,ISRAEL. RP FREEDMAN, LS (reprint author), NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892, USA. NR 5 TC 6 Z9 6 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 DEC 15 PY 1991 VL 134 IS 12 BP 1472 EP 1473 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA HC444 UT WOS:A1991HC44400017 ER PT J AU OKA, H IKAI, Y KAWAMURA, N HAYAKAWA, J HARADA, K MURATA, H SUZUKI, M ITO, Y AF OKA, H IKAI, Y KAWAMURA, N HAYAKAWA, J HARADA, K MURATA, H SUZUKI, M ITO, Y TI DIRECT INTERFACING OF HIGH-SPEED COUNTERCURRENT CHROMATOGRAPHY TO FRIT ELECTRON IONIZATION, CHEMICAL IONIZATION, AND FAST-ATOM-BOMBARDMENT MASS-SPECTROMETRY SO ANALYTICAL CHEMISTRY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; COIL PLANET CENTRIFUGE; MACROLIDE ANTIBIOTICS; NATURAL-PRODUCTS; SEPARATION; MYCINAMICINS; ACIDS AB Direct interfacing of analytical high-speed countercurrent chromatography (HSCCC) to mass spectrometry (MS) was demonstrated for the first time, and its performance was evaluated in terms of chromatography and mass spectrometry. HSCCC/MS interface was based upon Frit electron ionization (EI), chemical ionization (CI), and fast atom bombardment (FAB). Separations were conducted by newly developed HSCCC-4000 with a 2.5-cm revolutional radius and 0.3 mm or 0.55 mm i.d. multilayer coiled column which is capable of operating at a maximum speed of 4000 rpm. To demonstrate the potential capability of HSCCC/frit MS, three indole auxin mixtures, two mycinamicin (macrolide antibiotics) mixtures, and a colistin complex (peptide antibiotics) were analyzed under HSCCC/frit EI, CI, and FABMS conditions, respectively. The data obtained indicated that interfacing to frit/MS does not adversely affect the chromatographic resolution and mass spectra provide structural information. The HSCCC system interfaced with a frit-equipped mass spectrometer will offer a new dimension in the separation of biologically important substances. C1 MEIJO UNIV,FAC PHARM,TEMPA KU,NAGOYA,AICHI 468,JAPAN. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. RP OKA, H (reprint author), AICHI PREFECTURAL INST PUBL HLTH,TSUJI MACHI,KITA KU,NAGOYA 462,JAPAN. NR 29 TC 32 Z9 33 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD DEC 15 PY 1991 VL 63 IS 24 BP 2861 EP 2865 DI 10.1021/ac00024a011 PG 5 WC Chemistry, Analytical SC Chemistry GA GU987 UT WOS:A1991GU98700011 PM 1789450 ER PT J AU SACHER, RA MELPOLDER, JJ ALTER, HJ AF SACHER, RA MELPOLDER, JJ ALTER, HJ TI HEPATITIS-C VIRUS AND FULMINANT-HEPATITIS SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 NIH,BETHESDA,MD 20892. RP SACHER, RA (reprint author), GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007, USA. NR 1 TC 6 Z9 6 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 DEC 15 PY 1991 VL 115 IS 12 BP 984 EP 985 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA GU417 UT WOS:A1991GU41700020 ER PT J AU BRIGHTMAN, M AF BRIGHTMAN, M TI IMPLICATION OF ASTROGLIA IN THE BLOOD-BRAIN-BARRIER SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID ENDOTHELIAL-CELLS INVITRO; ORTHOGONAL ARRAYS; TIGHT JUNCTIONS RP BRIGHTMAN, M (reprint author), NIH, DEPT HLTH & HUMAN SERV, BETHESDA, MD 20892 USA. NR 23 TC 0 Z9 0 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PD DEC 15 PY 1991 VL 633 BP 343 EP 347 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM205 UT WOS:A1991JM20500038 ER PT J AU YAGINUMA, Y WESTPHAL, H AF YAGINUMA, Y WESTPHAL, H TI ANALYSIS OF THE P53 GENE IN HUMAN UTERINE CARCINOMA CELL-LINES SO CANCER RESEARCH LA English DT Article ID HUMAN PAPILLOMAVIRUS TYPE-16; TUMOR-ANTIGEN; CANCER; MUTATIONS; EXPRESSION; SEQUENCES; RECEPTOR; PROTEIN; OCCUR AB The inactivation of the tumor suppressor gene p53 has been demonstrated in a variety of human tumors. In this study, we present a p53 gene analysis of 13 uterine carcinoma cell lines. Sequencing analysis of the entire coding region revealed mutations changing the p53 amino acid composition in all six endometrial carcinoma cell lines tested (Ishikawa, Hecl-A, necl-B, KLE, RL95-2, and AN-3). Of the seven cervical carcinoma cell lines, two (HT-3 and C-33A) contained p53 codon changes as well. We were unable to detect human papillomavirus in these two cell lines. By contrast, five human papillomavirus-positive cervical carcinoma cell lines (HeLa S-3, Caski, SiHa, C-4I, and ME-180) contained wild-type p53 gene sequences. We suggest that, in the human papillomavirus-positive cervical tumors, p53 inactivation occurred via the known mechanism of viral E6/cellular p53 protein association, whereas in all other tumors p53 function was compromised by changes in the amino acid sequence. RP YAGINUMA, Y (reprint author), NICHHD,MAMMALIAN GENES & DEV LAB,BETHESDA,MD 20892, USA. NR 35 TC 100 Z9 100 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1991 VL 51 IS 24 BP 6506 EP 6509 PG 4 WC Oncology SC Oncology GA GU416 UT WOS:A1991GU41600002 PM 1660340 ER PT J AU HENDERSON, J SEBAG, M RHIM, J GOLTZMAN, D KREMER, R AF HENDERSON, J SEBAG, M RHIM, J GOLTZMAN, D KREMER, R TI DYSREGULATION OF PARATHYROID HORMONE-LIKE PEPTIDE EXPRESSION AND SECRETION IN A KERATINOCYTE MODEL OF TUMOR PROGRESSION SO CANCER RESEARCH LA English DT Article ID HUMORAL HYPERCALCEMIA; CELL-LINE; GROWTH-FACTOR; PROTEIN; GENE; MALIGNANCY; IDENTIFICATION; CANCER; 1,25-DIHYDROXYVITAMIN-D3; DIFFERENTIATION AB Using a human keratinocyte model of tumor progression, we have examined the regulation of gene expression and secretion of a parathyroid hormone-like peptide (PLP) that has been implicated in the pathogenesis of hypercalcemia in cancer. A rapid and transient induction of PLP mRNA in response to serum stimulation was demonstrated in both established (HPK1A) and malignant (HPK1A-ras) cells; however the dose dependent increases were greater in HPK1A than in HPK1A-ras. Significant inhibition of this induction was noted with the addition of 1,25-dihydroxyvitamin D3 at a lower concentration in HPK1A than in HPK1A-ras. Amino-terminal PLP immunoreactivity and bioactivity correlated well (r = 0.98) when measured in conditioned medium. In the absence of mitogenic stimuli, malignant keratinocytes (HPK1A-ras) secreted significantly more PLP than established (HPK1A) keratinocytes. However, in response to increasing concentrations of epidermal growth factor and fetal bovine serum, PLP release was far greater from HPK1A (maximum 13 x basal) than from HPK1A-ras (maximum 3 x basal) cells. In addition, 1,25-dihydroxyvitamin D3 was more effective in inhibiting both basal and stimulated PLP secretion in HPK1A than in HPK1A-ras cultures. Reduction of extracellular Ca" from 2.0 mm to 0.5 mm appeared to be more effective at an early time point in reducing PLP secretion from the established cells compared with the malignant cells. These studies therefore demonstrate a progressive dysregulation of PLP expression and secretion in human keratinocytes in the transformation from established to malignant phenotype and may have important implications for understanding the pathogenetic mechanisms involved in vivo in the development of hypercalcemia in cancer. C1 MCGILL UNIV,DEPT MED,MONTREAL H3A 2T5,QUEBEC,CANADA. MCGILL UNIV,DEPT PHYSIOL,MONTREAL H3A 2T5,QUEBEC,CANADA. NCI,DEPT CELLULAR & MOLEC BIOL,BETHESDA,MD 20892. NR 49 TC 79 Z9 79 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1991 VL 51 IS 24 BP 6521 EP 6528 PG 8 WC Oncology SC Oncology GA GU416 UT WOS:A1991GU41600005 PM 1742725 ER PT J AU OCONNOR, PM WASSERMANN, K SARANG, M MAGRATH, I BOHR, VA KOHN, KW AF OCONNOR, PM WASSERMANN, K SARANG, M MAGRATH, I BOHR, VA KOHN, KW TI RELATIONSHIP BETWEEN DNA CROSS-LINKS, CELL-CYCLE, AND APOPTOSIS IN BURKITT-LYMPHOMA CELL-LINES DIFFERING IN SENSITIVITY TO NITROGEN-MUSTARD SO CANCER RESEARCH LA English DT Article ID C-MYC-ONCOGENE; L-PHENYLALANINE MUSTARD; METHYLENE DIMETHANESULFONATE; HYDROLYTIC PRODUCT; CYTO-TOXICITY; TRANSLOCATION; LEUKEMIA; LOCUS; CIS-DIAMMINEDICHLOROPLATINUM(II); AMPLIFICATION AB We surveyed 11 Burkitt's lymphoma cell lines for chemosensitivity to nitrogen mustard (HN2) in order to determine whether any simple correlates to cytotoxic response might be revealed. The lines tested varied over a 5-fold range in concentration of HN2 required to inhibit tumor cell growth by 50%. Drug sensitivity correlated neither with continental origin of tumor, growth fraction, presence of Epstein-Barr virus, nor with the precise locations of (8;14) translocation breakpoints. Furthermore, contrary to experience with other cell lines, no simple correlation was found between the HN2 sensitivity of the four most divergent lines (low sensitivity, CA46 and MC116 cells; high sensitivity, Namalwa and JLP119 cells) and exposure to DNA cross-links (area under the DNA cross-linking-versus-time curve). In addition, we found similar extents of gene-specific HN2-induced damage in the native and translocated c-myc alleles of CA46 and JLP119 cells. At equimolar HN2 treatment, CA46 cells exhibited a profound arrest in G2M phase, while JLP119 cells exhibited prolonged S-phase delay. This suggested that despite similar DNA cross-link exposure, JLP119 cells were less able to complete DNA replication while repair was in progress. As cell cycle distribution returned to near normal, JLP119 cells exhibited DNA degradation characterized by oligonucleosome-sized DNA fragments prior to cell membrane disintegration. Our findings indicate that HN2-sensitive Burkitt's lymphoma cells may be more susceptible to delay in S phase for a given frequency of DNA cross-links and that prolongation of S phase correlated with apoptotic cell death. RP OCONNOR, PM (reprint author), NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,BLDG 37,ROOM 5C25,BETHESDA,MD 20892, USA. NR 44 TC 92 Z9 92 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1991 VL 51 IS 24 BP 6550 EP 6557 PG 8 WC Oncology SC Oncology GA GU416 UT WOS:A1991GU41600009 PM 1742728 ER PT J AU FUTAMI, H EADER, LA KOMSCHLIES, KL BULL, R GRUYS, ME ORTALDO, JR YOUNG, HA WILTROUT, RH AF FUTAMI, H EADER, LA KOMSCHLIES, KL BULL, R GRUYS, ME ORTALDO, JR YOUNG, HA WILTROUT, RH TI FLAVONE ACETIC-ACID DIRECTLY INDUCES EXPRESSION OF CYTOKINE GENES IN MOUSE SPLENIC LEUKOCYTES BUT NOT IN HUMAN PERIPHERAL-BLOOD LEUKOCYTES SO CANCER RESEARCH LA English DT Article ID TUMOR-NECROSIS-FACTOR; MURINE RENAL-CANCER; NATURAL-KILLER ACTIVITY; ADVANCED MALIGNANT-MELANOMA; LARGE GRANULAR LYMPHOCYTES; RECOMBINANT INTERLEUKIN-2 RIL-2; INTERFERON-GAMMA PRODUCTION; IFN-GAMMA; ANTITUMOR-ACTIVITY; IMMUNE INTERFERON AB Flavone-8-acetic acid (FAA) is a flavonoid drug that augments mouse natural killer activity, induces cytokine gene expression, and synergizes with recombinant interleukin 2 for the treatment of murine renal cancer. However, FAA has been largely inactive in human clinical trials. In the present study we investigated the ability of FAA treatment to directly induce cytokine mRNA expression in total mouse splenic leukocytes and selected leukocyte subsets, as well as in total human peripheral blood leukocytes. Analysis of RNA isolated from FAA-treated mouse splenic leukocytes demonstrated that treatment with greater-than-or-equal-to 100-mu-g/ml of FAA induced expression of tumor necrosis factor-alpha (TNF-alpha) mRNA by 1 h and induced maximal expression of TNF-alpha, alpha-interferon, and gamma-interferon mRNA within 3 h. The expression of all cytokine genes was diminished by 6 h. Interferon biological activity was detected in the supernatants of mouse splenic or peripheral blood leukocytes after treatment with FAA. These results correlate well with the previously reported induction of cytokine mRNA genes and biological activity by FAA in vivo. In contrast, FAA did not induce detectable mRNA expression or cytokine protein secretion by human peripheral blood leukocytes under similar conditions. These results demonstrate that FAA can directly stimulate cytokine gene expression in mouse but not in human leukocytes. Further studies performed with highly purified positively selected mouse CD4+ or CD8+ splenic T-lymphocytes, as well as purified B-cells, demonstrated that the FAA-induced expression of gamma-interferon mRNA was mainly induced in the CD8+ lymphocyte subset. alpha-Interferon mRNA was expressed largely in the B-cell population, while TNF-alpha mRNA was induced in all leukocyte subsets tested. Therefore, these results suggest that the immunomodulatory effects of FAA in mice are direct, but different cytokines are induced from different leukocyte subsets. Further, the data suggest that flavonoid compounds or analogues that stimulate cytokine gene expression in human cells might be therapeutically active in cancer patients. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74102] NR 51 TC 40 Z9 41 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1991 VL 51 IS 24 BP 6596 EP 6602 PG 7 WC Oncology SC Oncology GA GU416 UT WOS:A1991GU41600017 PM 1742732 ER PT J AU KRISHNA, MC DEGRAFF, W TAMURA, S GONZALEZ, FJ SAMUNI, A RUSSO, A MITCHELL, JB AF KRISHNA, MC DEGRAFF, W TAMURA, S GONZALEZ, FJ SAMUNI, A RUSSO, A MITCHELL, JB TI MECHANISMS OF HYPOXIC AND AEROBIC CYTOTOXICITY OF MITOMYCIN-C IN CHINESE-HAMSTER V79 CELLS SO CANCER RESEARCH LA English DT Article ID ELECTRON-SPIN-RESONANCE; DT-DIAPHORASE; TUMOR-CELLS; HYDROGEN-PEROXIDE; CROSS-LINKING; FREE-RADICALS; DNA; ACTIVATION; CANCER; CHEMOTHERAPY AB Mitomycin C (MMC) induced aerobic and hypoxic cytotoxicity in Chinese hamster V79 cells was studied to evaluate the role of the 1-electron versus 2-electron reductive bioactivation. Superoxide dismutase, catalase, and desferal had no protective effects on the aerobic or hypoxic cytotoxicity of MMC, whereas Tempol and Tempol-H, which are known to interrupt and terminate radical reactions, provided partial protection under aerobic conditions. However, under hypoxic conditions, Tempol provided complete protection whereas Tempol-H was ineffective. Electron paramagnetic resonance and spin-trapping investigations, designed to study the mechanisms of such protective effects, confirmed that MMC is activated by the human NADPH:cytochrome P-450 oxidoreductase to its semiquinone radical and that, under aerobic conditions, the semiquinone radical reduces molecular oxygen. Under hypoxic conditions, the semiquinone of MMC reduces H2O2 to produce OH radicals as detected by electron paramagnetic resonance-spin trapping with 5,5-dimethyl-1-pyrroline N-oxide. The 1-electron reduced product of MMC was also found to reduce Tempol to the hydroxylamine, Tempol-H, whereas oxidation of Tempol-H by MMC approximately equal to was negligible. Cell survival studies and electron paramagnetic resonance observations indicate that the hypoxic cytotoxicity of MMC is mediated by 1-electron activation to its semiquinone intermediate. Under aerobic conditions, the steady state concentration of this intermediate is low due to the facile autooxidation of the semiquinone producing O2 approximately equal to and H2O2 which are capable of causing oxidative cytotoxicity. Tempol, which can accept an electron from reducing radical species, completely inhibited the hypoxic cytotoxicity of MMC indicating MMC approximately equal to the semiquinone of MMC as the species responsible for DNA alkylation and selective hypoxic cytotoxicity of MMC. Our results also indicate that the aerobic cytotoxicity is mediated by other processes in addition to the 1-electron mediated activation. C1 NCI,RADIAT ONCOL BRANCH,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,SCH MED,JERUSALEM,ISRAEL. NR 41 TC 73 Z9 73 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1991 VL 51 IS 24 BP 6622 EP 6628 PG 7 WC Oncology SC Oncology GA GU416 UT WOS:A1991GU41600021 PM 1660344 ER PT J AU JOHNSTON, PG LIANG, CM HENRY, S CHABNER, BA ALLEGRA, CJ AF JOHNSTON, PG LIANG, CM HENRY, S CHABNER, BA ALLEGRA, CJ TI PRODUCTION AND CHARACTERIZATION OF MONOCLONAL-ANTIBODIES THAT LOCALIZE HUMAN THYMIDYLATE SYNTHASE IN THE CYTOPLASM OF HUMAN-CELLS AND TISSUE SO CANCER RESEARCH LA English DT Article ID MOUSE FIBROBLASTS; ESCHERICHIA-COLI; SYNTHETASE; GENE; CANCER; 5-FLUOROURACIL; CHEMOTHERAPY; EXPRESSION; CARCINOMA; BINDING AB Thymidylate synthase (TS; EC 2.1.1.45) is an important cellular enzyme that converts dUMP to dTMP, which is essential for DNA biosynthesis. In addition, TS is an important cellular target for the fluoropyrimidine cytotoxic drugs that are widely used in the treatment of solid tumors. We have generated five monoclonal antibodies against human TS using a recombinant human TS enzyme. These antibodies react specifically with human TS and display negligible cross-reactivity with other cellular proteins found in human cells. Binding affinity studies demonstrate that all antibodies form a tight interaction with recombinant human TS enzyme (K(d) range = 0.3-11.0 nM). All antibodies display reactivity on enzyme-linked immunosorbent assay and immunoprecipitation. On Western blot analysis each detects a protein of approximately 36 kDa molecular mass under denaturing conditions. In addition to their reactivity on immunoprecipitation and Western analysis, two of the antibodies, TS 106 and TS 109, are reactive on immunohistochemical staining of human colon carcinoma cell lines and tissue, producing a granular cytoplasmic staining pattern. Specificity for TS is demonstrated by the lack of staining with preimmune IgG and the disappearance of the signal when the antibodies are preabsorbed with recombinant human TS enzyme. Quantitation of TS by Western blot analysis and biochemical FdUMP binding assay in 5-fluorouracil-resistant colon carcinoma cell lines (NCI H630R10, NCI H630R1) and a sensitive colon carcinoma cell line (NCI H630) revealed a 36- and 6-fold increase in TS in the resistant cell line as measured by the biochemical assay compared to a 39- and 10.6-fold increase as measured by densitometric analysis of the Western blot. These comparative studies of immunohistochemical, Western, and biochemical analyses reveal that the immunological detection of TS in human colon cell lines is a sensitive and quantitative assay. Thus the ability of these antibodies to detect TS in human cancer cells and tissue may allow measurement of TS in human tissues by quantitative immunohistochemistry in studies of drug resistance and for determination of proliferative rates. C1 US FDA,CTR BIOL EVALUAT & RES,DIV BACTERIAL PROD,BETHESDA,MD 20892. RP JOHNSTON, PG (reprint author), NCI,DIV CANC TREATMENT,MED BRANCH,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 41 TC 130 Z9 134 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1991 VL 51 IS 24 BP 6668 EP 6676 PG 9 WC Oncology SC Oncology GA GU416 UT WOS:A1991GU41600028 PM 1720706 ER PT J AU COLE, HBR TORCHIA, DA AF COLE, HBR TORCHIA, DA TI AN NMR-STUDY OF THE BACKBONE DYNAMICS OF STAPHYLOCOCCAL NUCLEASE IN THE CRYSTALLINE STATE SO CHEMICAL PHYSICS LA English DT Article ID N-15 CHEMICAL-SHIFT; MAGNETIC-RESONANCE RELAXATION; MODEL-FREE APPROACH; SPIN RELAXATION; SPECTROSCOPY; C-13; INTERLEUKIN-1-BETA; PROTEINS; ASSIGNMENT; SPECTRA AB We report cross polarization magic angle spinning spectra of crystals of staphylococcal nuclease complexed with pdTp and Ca2+, and labeled with either [N-15]His or [N-15]Val. With the exceptions of His46 and Val51, residues which are in the OMEGA-loop at the active site of the enzyme, signals of all His and Val amide nitrogen spins are observed at the chemical shift positions found in the solution spectra of the ternary complex. The absence of signals from His46 and Val51 in the solid state spectra is evidence that these residues are mobile and disordered. The coincidence of the solution and crystalline chemical shifts for the remaining residues is evidence that these residues have the same backbone conformations in solution and in the crystalline states, and allows us to extend the sequential assignments obtained in solution to the solid state. The spin lattice relaxation rates of the assigned His and Val amide nitrogen spins exhibit a wide range of values that correlate reasonably well with B values derived from X-ray data. Correlation times derived from the measurements of spin lattice relaxation rates at 5.9 T and 11.8 T are in the range 10-10(3) ps, suggesting that the relaxation data could provide useful tests of calculated SNase molecular dynamics trajectories. RP COLE, HBR (reprint author), NIDR,BONE RES BRANCH,BETHESDA,MD 20892, USA. NR 37 TC 69 Z9 71 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0104 J9 CHEM PHYS JI Chem. Phys. PD DEC 15 PY 1991 VL 158 IS 2-3 BP 271 EP 281 DI 10.1016/0301-0104(91)87071-3 PG 11 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA GT766 UT WOS:A1991GT76600007 ER PT J AU STEINBACH, PJ LONCHARICH, RJ BROOKS, BR AF STEINBACH, PJ LONCHARICH, RJ BROOKS, BR TI THE EFFECTS OF ENVIRONMENT AND HYDRATION ON PROTEIN DYNAMICS - A SIMULATION STUDY OF MYOGLOBIN SO CHEMICAL PHYSICS LA English DT Article ID MOLECULAR-DYNAMICS; NEUTRON-SCATTERING; TEMPERATURE-DEPENDENCE; ATOMIC DISPLACEMENTS; FERROCYTOCHROME-C; METMYOGLOBIN; CRYSTALS; DEOXYMYOGLOBIN; ANHARMONICITY; DIFFRACTION AB Three classes of molecular dynamics (MD) simulations of carboxy-myoglobin (MbCO) have been performed to investigate the environmental and temperature dependence of protein dynamics. The first class examines the effects of hydration. Simulations of MbCO were performed at 100 and 300 K with 0, 35, 100, 349, and 999 water molecules, and at 300 K with 3832 water molecules. The second class considers a cluster of three partially hydrated MbCO molecules (349 waters each) at 100, 180, 240, and 300 K. The third class of simulations, performed at 100 and 300 K, examines hydration by D2O and also the effects of different vacuum models and long-range electrostatic cutoff methods. The simulations generally consist of 200 ps of heating and equilibration followed by 100 ps of dynamics used for analysis. Atomic fluctuation is compared to neutron scattering data to better determine the type of calculation needed to reproduce the low-temperature behavior of proteins. The simulations of hydrated myoglobin indicate that as the hydration increases: (i) agreement with the X-ray structure improves, (ii) the number of heavy-atom dihedral transitions decreases at both 100 and 300 K, and (iii) atomic fluctuations decrease at 100 K but increase at 300 K. The cluster and deuterated simulations exhibit atomic fluctuations at 100 K similar to, but slightly reduced from, those of a single hydrate myoglobin. Thus, our previous observation from MD simulations of low-temperature mean-square fluctuation three times larger than that observed experimentally does not appear to be due to the mass of the water model, nor the complete absence of intermolecular protein-protein contacts. C1 ELI LILLY & CO,SUPERCOMP APPLICAT & MOLEC DESIGN,INDIANAPOLIS,IN 46285. RP STEINBACH, PJ (reprint author), NIH,DIV COMP RES & TECHNOL,MOLEC GRAPH & SIMULAT LAB,BETHESDA,MD 20892, USA. NR 24 TC 82 Z9 82 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0104 J9 CHEM PHYS JI Chem. Phys. PD DEC 15 PY 1991 VL 158 IS 2-3 BP 383 EP 394 DI 10.1016/0301-0104(91)87078-A PG 12 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA GT766 UT WOS:A1991GT76600014 ER PT J AU KERR, JM FISHER, LW TERMINE, JD YOUNG, MF AF KERR, JM FISHER, LW TERMINE, JD YOUNG, MF TI THE CDNA CLONING AND RNA DISTRIBUTION OF BOVINE OSTEOPONTIN SO GENE LA English DT Article DE CDNA SEQUENCE; BONE SIALOPROTEIN-I; TRANSFORMATION-ASSOCIATED PHOSPHOPROTEIN; 44K BONE PHOSPHOPROTEIN; SECRETED PHOSPHOPROTEIN; CELL ADHESION PROTEIN ID 44-KILODALTON BONE PHOSPHOPROTEIN; SMALL PROTEOGLYCAN-I; RAT-KIDNEY CELLS; DEVELOPMENTAL EXPRESSION; SECRETED PHOSPHOPROTEIN; PHYSIOLOGICAL-PROPERTIES; NONPHOSPHORYLATED FORMS; FIBROBLAST ATTACHMENT; NUCLEOTIDE-SEQUENCE; SIALOPROTEIN-II AB We have isolated and sequenced the bovine cDNA (OPN) counterpart of osteopontin. The cDNA is 1356 nucleotides (nt) in length with an open reading frame of 834 nt, encoding a 278-amino acid (aa) protein. Cell-free transcription and translation of OPN RNA resulted in a major species of approx. 40 kDa in size, in agreement with the predicted size of the deduced aa sequence. Northern analysis of bovine OPN RNA indicated the presence of the message in mineralized, as well as soft tissues. A comparison of the deduced aa sequence among various species indicates both regions of similarity and divergence. One prominent region of dissimilarity in bovine OPN compared to all other species is a 22-aa gap which may represent a loss of a potential Ca2+-binding loop. Despite the variability among the species, several regions of conservation are apparent, including a hydrophobic leader sequence, a potential site for Asn-linked glycosylation, a stretch of polyaspartic acid residues, and the cell attachment Arg-Gly-Asp tripeptide. Whether bovine OPN enhances cell attachment is unknown. Furthermore, whether the loss of a potential Ca2+-binding loop alters the function of OPN would be interesting to determine. RP KERR, JM (reprint author), NIDR,BONE RES BRANCH,BLDG 30,RM 106,BETHESDA,MD 20892, USA. NR 34 TC 64 Z9 65 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 DEC 15 PY 1991 VL 108 IS 2 BP 237 EP 243 DI 10.1016/0378-1119(91)90439-I PG 7 WC Genetics & Heredity SC Genetics & Heredity GA GW534 UT WOS:A1991GW53400009 PM 1721033 ER PT J AU BODENTEICH, A MITCHELL, LG MERRILL, CR AF BODENTEICH, A MITCHELL, LG MERRILL, CR TI A LIFETIME OF RETINAL LIGHT EXPOSURE DOES NOT APPEAR TO INCREASE MITOCHONDRIAL MUTATIONS SO GENE LA English DT Note DE RECOMBINANT DNA; D-LOOP; POSTMITOTIC; CYTOCHROME OXIDASE-III; TRANSFER RNA GLYCINE; NADH DEHYDROGENASE; DNA REPAIR; HUMAN; MITOCHONDRIAL HETEROPLASMY ID KEARNS-SAYRE SYNDROME; DNA; SEQUENCE; TISSUES; GENOME; RAT; PURIFICATION; RADIATION; DELETIONS; STRIATUM AB Recently, there have been a number of reports of an accumulation of mutations in the mitochondrial (mt) genome with age. Such mutations may be due in part to the mt oxidative metabolic pathways which provide most of the cell's energy, but also generate free radicals. In addition, the mt genome in some tissues, such as the retina, may also accumulate mutations from the effects of ultraviolet light. To obtain information concerning the possible accumulation of retinal mt mutations with age, we cloned retinal mt DNA from a 71-year-old person. Thirty-two kilobases of sequence from 83 independently isolated clones representing two regions, a coding and a noncoding region, of the mt genome were obtained. Three polymorphisms between these sequences and the standard 'Anderson sequence' were discovered. Only one heteroplasmic mutation was found. These results confirm the low somatic mutation rate found in prior studies utilizing different types of human tissues. In addition, these results suggest that there is little if any accumulated damage to the mt DNA of the retina during normal aging. C1 NIMH,CTR NEUROSCI,BIOCHEM GENET LAB,2700 MARTIN LUTHER KING AVE,WASHINGTON,DC 20032. NR 41 TC 21 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD DEC 15 PY 1991 VL 108 IS 2 BP 305 EP 309 DI 10.1016/0378-1119(91)90451-G PG 5 WC Genetics & Heredity SC Genetics & Heredity GA GW534 UT WOS:A1991GW53400021 PM 1660842 ER PT J AU TAN, GT KINGHORN, AD HUGHES, SH PEZZUTO, JM AF TAN, GT KINGHORN, AD HUGHES, SH PEZZUTO, JM TI PSYCHOTRINE AND ITS O-METHYL ETHER ARE SELECTIVE INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS-1 REVERSE-TRANSCRIPTASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACID POLYMERASES; DIFFERENTIAL INHIBITION; ESCHERICHIA-COLI; DNA-POLYMERASES; AIDS; FAGARONINE; PURIFICATION; APHIDICOLIN; SURAMIN; DOMAIN AB Psychotrine dihydrogen oxalate and O-methylpsychotrine sulfate heptahydrate (MP), the salts of isoquinoline alkaloids from ipecac, were found to be potent inhibitors of the DNA polymerase activity of human immunodeficiency virus-1 reverse transcriptase (HIV-1 RT). We currently report the results of additional studies designed to characterize the mechanism of inhibition facilitated by MP. The inhibition was noncompetitive with respect to TTP and uncompetitive with respect to poly(rA) and oligo(dT)12-18 (4:1) at low template-primer concentrations but competitive at high concentrations (> 200-mu-M). Identical non-Michaelis-type kinetics were observed when activated DNA was used as the template. The biphasic nature of the double-reciprocal plots and Hill coefficients of less than 1 indicate that MP functions as an allosteric inhibitor of the enzyme which appears to possess multiple active sites that interact in a cooperative (negative) fashion in the presence of the inhibitor. MP was selective for the recombinant HIV-1 RT (p66) utilizing poly(rA) and oligo(dT)12-18 (4:1) as template-primer. Greater inhibition was observed with this template primer as compared with other natural and synthetic template-primers tested. MP had significantly less effect on avian myeloblastosis virus RT as well as mammalian or bacterial DNA and RNA polymerases. Other members of the ipecac class of alkaloids, e.g. emetine hydrochloride, were inactive against all of these enzymes, including HIV-1 RT. Conversely, MP did not inhibit in vitro protein synthesis, a property manifested by all the other ipecac alkaloids tested. Studies conducted with structural analogs revealed that the imine functionality at positions 1' and 2' of MP is the key structural requirement for HIV-1 RT inhibitory activity. Therefore, MP appears to possess unique structural properties that enable interaction with HIV-1 RT in a manner that can be differentiated from other polymerases. Use of these alkaloids for the definition of this viral enzyme-specific topology may lead to the development of therapeutically useful chemotherapeutic agents. C1 UNIV ILLINOIS,COLL PHARM,PROGRAM COLLABORAT RES PHARMACEUT SCI M-C 877,833 S WOOD ST,CHICAGO,IL 60612. UNIV ILLINOIS,COLL PHARM,DEPT MED CHEM & PHARMACOGNOSY,CHICAGO,IL 60612. UNIV ILLINOIS,COLL MED,DIV SURG ONCOL,CHICAGO,IL 60612. NCI,FREDERICK CANC RES & DEV CTR,ABL INC,BASIC RES PROGRAM,FREDERICK,MD 21701. RP PEZZUTO, JM (reprint author), UNIV ILLINOIS,COLL PHARM,PROGRAM COLLABORAT RES PHARMACEUT SCI M-C 877,833 S WOOD ST,CHICAGO,IL 60612, USA. OI Kinghorn, A. Douglas/0000-0002-6647-8707 FU NCI NIH HHS [N01-CO-74101] NR 43 TC 30 Z9 30 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 15 PY 1991 VL 266 IS 35 BP 23529 EP 23536 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GV319 UT WOS:A1991GV31900004 PM 1721050 ER PT J AU OSHIMA, M SITHANANDAM, G RAPP, UR GUROFF, G AF OSHIMA, M SITHANANDAM, G RAPP, UR GUROFF, G TI THE PHOSPHORYLATION AND ACTIVATION OF B-RAF IN PC12-CELLS STIMULATED BY NERVE GROWTH-FACTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PC12 PHEOCHROMOCYTOMA CELLS; PROTEIN KINASE-C; TYROSINE PHOSPHORYLATION; SIGNAL TRANSDUCTION; CHROMAFFIN CELLS; FIBER OUTGROWTH; FAMILY; INCREASE; K-252A; DIFFERENTIATION AB Treatment of PC12 cells with nerve growth factor does not alter the levels of B-raf mRNA, but does induce rapid phosphorylation of B-raf proteins. Phosphorylation was observed after 1.5 min and reached a maximum by 10-15 min. B-raf protein was phosphorylated almost exclusively on serine residues; no tyrosine phosphorylation was detected. Nerve growth factor-induced phosphorylation was not affected by depletion of protein kinase C or by removal of extracellular calcium but was inhibited by K-252a. Concomitant with the increase in serine phosphorylation, nerve growth factor treatment also increased the serine/threonine kinase activity of B-raf protein within 1-2 min. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL PATHOL SECT,FREDERICK,MD 21702. RP OSHIMA, M (reprint author), NICHHD,GROWTH FACTORS SECT,BLDG 6,RM 130,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CO-74102] NR 58 TC 68 Z9 69 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 DEC 15 PY 1991 VL 266 IS 35 BP 23753 EP 23760 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GV319 UT WOS:A1991GV31900037 PM 1748651 ER PT J AU ZINN, SA EBERT, KM MEHTA, ND JOSHI, J KILPATRICK, DL AF ZINN, SA EBERT, KM MEHTA, ND JOSHI, J KILPATRICK, DL TI SELECTIVE TRANSCRIPTION OF RAT PROENKEPHALIN FUSION GENES FROM THE SPERMATOGENIC CELL-SPECIFIC PROMOTER IN TESTIS OF TRANSGENIC MICE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DIHYDROFOLATE-REDUCTASE PROMOTER; TISSUE-SPECIFIC EXPRESSION; BETA-GLOBIN GENES; MESSENGER-RNA; SOMATIC-CELLS; GERM-CELLS; KINASE; INITIATION; SEQUENCE; ELEMENT AB The rat and mouse proenkephalin genes each contains two distinct promoters, one of which is utilized exclusively by spermatogenic cells. The germ cell-specific promoter lacks TATA sequences, is G+C rich, and contains multiple initiation sites. To investigate the nature of the cis-acting elements that determine selective transcription of the proenkephalin gene in male germ cells, two rat proenkephalin-chloramphenicol acetyltransferase fusion genes containing the two different promoter regions as well as 1.6 or 0.3 kilobases, respectively, of 5'-flanking sequence were expressed in transgenic mice. Multiple transgenic lines were developed which expressed the fusion genes in testis, brain, and heart but not in tissues that do not normally express the proenkephalin gene. Fusion gene transcripts in transgenic mouse testes were localized to those spermatogenic cell types that utilize the spermatogenic cell promoter and were selectively and accurately initiated from the multiple rat germ cell start sites. Transgenic mice thus provide a useful model for the localization and characterization of cis-acting elements mediating transcription of the proenkephalin gene from its germ cell-specific promoter. C1 WORCESTER FDN EXPTL BIOL INC,NEUROBIOL GRP,222 MAPLE AVE,SHREWSBURY,MA 01545. NIH,BIOCHEM GENET LAB,BETHESDA,MD 20205. TUFTS UNIV,SCH VET MED,DEPT ANAT & CELL BIOL,N GRAFTON,MA 01536. TUFTS UNIV,SCH MED & DENT MED,DEPT ANAT & CELL BIOL,N GRAFTON,MA 01536. RP KILPATRICK, DL (reprint author), WORCESTER FDN EXPTL BIOL INC,NEUROBIOL GRP,222 MAPLE AVE,SHREWSBURY,MA 01545, USA. FU NIDDK NIH HHS [DK-36468] NR 43 TC 26 Z9 26 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 DEC 15 PY 1991 VL 266 IS 35 BP 23850 EP 23855 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GV319 UT WOS:A1991GV31900051 PM 1748659 ER PT J AU MUZZIN, P REVELLI, JP KUHNE, F GOCAYNE, JD MCCOMBIE, WR VENTER, JC GIACOBINO, JP FRASER, CM AF MUZZIN, P REVELLI, JP KUHNE, F GOCAYNE, JD MCCOMBIE, WR VENTER, JC GIACOBINO, JP FRASER, CM TI AN ADIPOSE TISSUE-SPECIFIC BETA-ADRENERGIC-RECEPTOR - MOLECULAR-CLONING AND DOWN-REGULATION IN OBESITY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MUSCARINIC CHOLINERGIC RECEPTORS; DIET-INDUCED THERMOGENESIS; SITE-DIRECTED MUTAGENESIS; PROTEIN MESSENGER-RNA; BETA-1-ADRENERGIC RECEPTOR; SEQUENCE-ANALYSIS; RAT; ADRENOCEPTOR; AGONIST; EXPRESSION AB Clones encoding an atypical beta-adrenergic receptor were isolated from a rat brown adipose tissue cDNA library. This receptor expressed in Chinese hamster ovary (CHO) cells displays a low affinity for beta-adrenergic antagonists and a high affinity for BRL 37344, an agonist that selectively stimulates lipolysis in adipose tissue. The rank order of potency for agonist-mediated increases in intracellular cAMP in transfected cells correlates with that for agonist-mediated stimulation of lipolysis in brown adipocytes. Northern blot analysis demonstrates that this receptor subtype is expressed only in brown and white adipose tissue where it represents the predominant beta-receptor subtype. The amount of atypical beta-adrenergic receptor present in adipose tissue of obese (fa/fa) Zucker rats is reduced by up to 71% as compared with lean (Fa/Fa) control animals. These findings suggest that a change in the expression of this beta-adrenergic receptor subtype may play a role in obesity. C1 NIAAA, PHYSIOL & PHARMACOL STUDIES LAB, MOLEC NEUROBIOL SECT, ROCKVILLE, MD 20852 USA. NINCDS, RECEPTOR BIOCHEM & MOLEC BIOL SECT, BETHESDA, MD 20892 USA. CTR MED UNIV GENEVA, DEPT BIOCHIM MED, CH-1211 GENEVA 4, SWITZERLAND. RP FRASER, CM (reprint author), NIAAA, PHYSIOL & PHARMACOL STUDIES LAB, MOLEC NEUROBIOL SECT, ROCKVILLE, MD 20852 USA. OI Fraser, Claire/0000-0003-1462-2428; McCombie, W. Richard/0000-0003-1899-0682 NR 37 TC 305 Z9 309 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 15 PY 1991 VL 266 IS 35 BP 24053 EP 24058 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GV319 UT WOS:A1991GV31900081 PM 1721063 ER PT J AU BRICKGHANNAM, C HUANG, FL TEMIME, N CHARRON, D AF BRICKGHANNAM, C HUANG, FL TEMIME, N CHARRON, D TI PROTEIN-KINASE-C (PKC) ACTIVATION VIA HUMAN-LEUKOCYTE ANTIGEN CLASS-II MOLECULES - A NOVEL REGULATION OF PKC ACTIVITY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID B-CELL ACTIVATION; RAT-BRAIN; MONOCLONAL-ANTIBODIES; IMMUNOCHEMICAL CHARACTERIZATION; RIBONUCLEIC-ACID; LYMPHOCYTES-B; T-CELLS; HLA; TRANSLOCATION; BINDING AB Analysis of intracellular localization of protein kinase C (PKC) in a lymphoblastoid B cell line shows that anti-human leucocyte antigen (HLA) class II antibodies induce an increase of cytosolic and membrane PKC activities. This phenomenon is both time- and dose-dependent. The maximal PKC activation was observed after exposure to 12.5-mu-g/ml antibody for 30 to 45 min. Unlike TPA, no translocation of the cytosolic PKC was observed at any time following exposure to the anti-HLA class II antibodies. We observed a good correlation between the [H-3]phorbol dibutyrate binding activity and the enzymatic activity of PKC. Using a panel of antibodies specific for the HLA class II isotypes (DP, DQ, DR), we demonstrated that PKC activation via HLA class II molecules is not restricted to one isotype. We also showed by Western blot analysis that the increased PKC activity correlates with a quantitative increase of PKC. The increase of PKC activity induced by anti-HLA class II antibodies was completly abolished by the treatment with actinomycin D, a transcriptional inhibitor, or cycloheximide, a translational inhibitor. Finally, Northern blot analysis revealed that anti-HLA class II antibodies induce an increase of the PKC-alpha and PKC-beta mRNAs levels which are significant after 20 min of stimulation and rose to a maximum after 60 min. In summary, our results show that increased PKC activity induced by HLA class II antibody is regulated at the transcriptional level. C1 NICHHD,BETHESDA,MD 20892. RP BRICKGHANNAM, C (reprint author), INST BIOMED CORDELIERS,IMMUNOGENET MOLEC LAB,15 RUE ECOLE MED,F-75006 PARIS,FRANCE. OI BRICK, CHEHRAZADE/0000-0002-7017-6533 NR 43 TC 33 Z9 33 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 15 PY 1991 VL 266 IS 35 BP 24169 EP 24175 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GV319 UT WOS:A1991GV31900098 PM 1748685 ER PT J AU TOMAREV, SI ZINOVIEVA, RD PIATIGORSKY, J AF TOMAREV, SI ZINOVIEVA, RD PIATIGORSKY, J TI CRYSTALLINS OF THE OCTOPUS LENS - RECRUITMENT FROM DETOXIFICATION ENZYMES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLUTATHIONE S-TRANSFERASES; MITOCHONDRIAL ALDEHYDE DEHYDROGENASE; FULL-LENGTH CDNA; NUCLEOTIDE-SEQUENCE; EYE LENS; PHYSICOCHEMICAL CHARACTERIZATION; EVOLUTIONARY STRATEGY; MESSENGER-RNA; HUMAN-LIVER; PROTEINS AB The eye lens crystallins of the octopus Octopus dofleini were identified by sequencing abundant proteins and cDNAs. As in squid, the octopus crystallins have subunit molecular masses of 25-30 kDa, are related to mammalian glutathione S-transferases (GST), and are encoded in at least six genes. The coding regions and deduced amino acid sequences of four octopus lens cDNAs are 75-80% identical, while their non-coding regions are entirely different. Deduced amino acid sequences show 52-57% similarity with squid GST-like crystallins, but only 20-25% similarity with mammalian GST. These data suggest that the octopus and squid lens GST-like crystallin gene families expanded after divergence of these species. Northern blot hybridization indicated that the four octopus GST-like crystallin genes examined are lens-specific. Lens extracts showed about 40 times less GST activity using 1-chloro-2,4-dinitrobenzene as substrate than liver extracts of the octopus, indicating that the major GST-like crystallins are specialized for a lens structural role. A prominent 59-kDa crystallin polypeptide, previously observed in octopus but not squid and called OMEGA-crystallin (Chiou, S.-H. (1988) FEBS Lett. 241, 261264), has been identified as an aldehyde dehydrogenase. Since cytoplasmic aldehyde dehydrogenase is a major protein in elephant shrew lenses (eta-crystallin; Wistow, G., and Kim, H. (1991) J. MoL Evol. 32, 262-269) the octopus aldehyde dehydrogenase crystallin provides the first example of a similar enzyme-crystallin in vertebrates and invertebrates. The use of detoxification stress proteins (GST and aldehyde dehydrogenase) as cephalopod crystallins indicates a common strategy for recruitment of enzyme-crystallins during the convergent evolution of vertebrate and invertebrate lenses. For historical reasons we propose that the octopus GST-like crystallins, like those of the squid, are called S-crystallins. RP TOMAREV, SI (reprint author), NEI,MOLEC & DEV BIOL LAB,BLDG 6,RM 207,BETHESDA,MD 20892, USA. NR 50 TC 57 Z9 63 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 15 PY 1991 VL 266 IS 35 BP 24226 EP 24231 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GV319 UT WOS:A1991GV31900106 PM 1721068 ER PT J AU MATZINGER, P AF MATZINGER, P TI THE JAM TEST - A SIMPLE ASSAY FOR DNA FRAGMENTATION AND CELL-DEATH SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE APOPTOSIS; CELL LYSIS; CELL DEATH; CYTOTOXIC T-CELLS; CR-51 RELEASE; [H-3]THYMIDINE AB Most current methods for measuring cell death are based on plasma membrane disintegration and the consequent release of cytoplasm. The relevant cells are usually loaded with a label (usually Cr-51 or I-125), the release of which is measured. I describe here a method, based on the recent evidence that dying cells often degrade their DNA into small fragments, which measures the DNA retained by living cells rather than the cellular components lost by dying cells. The assay is set up essentially like the current cell lysis assays and harvested like a cell proliferation assay. It is faster, more sensitive, easier to set up, less expensive and safer than the current standard Cr-51 release assay. RP MATZINGER, P (reprint author), NIH,INST ALLERGY & INFECT DIS,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 6 TC 583 Z9 598 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD DEC 15 PY 1991 VL 145 IS 1-2 BP 185 EP 192 DI 10.1016/0022-1759(91)90325-A PG 8 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA GW050 UT WOS:A1991GW05000022 PM 1765650 ER PT J AU MUELLER, DL CHIODETTI, L BACON, PA SCHWARTZ, RH AF MUELLER, DL CHIODETTI, L BACON, PA SCHWARTZ, RH TI CLONAL ANERGY BLOCKS THE RESPONSE TO IL-4, AS WELL AS THE PRODUCTION OF IL-2, IN DUAL-PRODUCING T-HELPER CELL CLONES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTIGEN-PRESENTING CELLS; AUTOCRINE GROWTH-FACTOR; STIMULATORY FACTOR-I; KINASE-C ACTIVATION; LYMPHOCYTES-T; MONOCLONAL-ANTIBODY; LYMPHOKINE PRODUCTION; COSTIMULATORY SIGNAL; ANTI-CD3 ANTIBODY; SELF-TOLERANCE AB In this report we extend the in vitro clonal anergy model to examine the regulation of proliferation in T cells that secrete both IL-2 and IL-4. Newly cloned Ag-specific murine T cells are shown to depend on both IL-2 and IL-4 synthesis for maximal proliferation. Whereas IL-2 responsiveness is constitutive in these cells, IL-4 responsiveness develops only after Ag and APC stimulation. Remarkably, proliferation of these cells to Ag is sensitive to inhibition by clonal anergy, even though IL-4 synthesis remains inducible. Anergy in these cells is associated with an inability to respond to IL-4, in addition to the development of an IL-2 production defect. The results suggest that anergy induction may be capable of preventing the clonal expansion of autoreactive T cells producing both IL-2 and IL-4 in vivo. C1 UNIV TEXAS,SW MED CTR,HAROLD C SIMMONS ARTHRITIS RES CTR,DALLAS,TX 75235. NIAID,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892. NIAID,SW MED CTR,DEPT INTERNAL MED,BETHESDA,MD 20892. UNIV BIRMINGHAM,DEPT RHEUMATOL,BIRMINGHAM B15 2TJ,W MIDLANDS,ENGLAND. RP MUELLER, DL (reprint author), UNIV TEXAS,SW MED CTR,DIV RHEUMAT DIS,DEPT INTERNAL MED,DALLAS,TX 75235, USA. OI Mueller, Daniel/0000-0003-1621-0419 FU NIAMS NIH HHS [2-T32-AR07055] NR 47 TC 78 Z9 78 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 DEC 15 PY 1991 VL 147 IS 12 BP 4118 EP 4125 PG 8 WC Immunology SC Immunology GA GW031 UT WOS:A1991GW03100011 PM 1836479 ER PT J AU AKSENTIJEVICH, I SACHS, DH SYKES, M AF AKSENTIJEVICH, I SACHS, DH SYKES, M TI NATURAL ANTIBODIES CAN INHIBIT BONE-MARROW ENGRAFTMENT IN THE RAT-]MOUSE SPECIES COMBINATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NONLETHAL PREPARATIVE REGIMEN; T-CELL DEPLETION; MONOCLONAL-ANTIBODIES; IMMUNE-DEFICIENCY; RAT LYMPHOCYTES; GRAFT-REJECTION; MICE; TOLERANCE; CHIMERISM; SKIN AB Specific tolerance can be induced in animals by transplanting hemopoietic cells across concordant species barriers. Despite the fact that the rat-mouse species combination is considered concordant, we have recently demonstrated that normal murine serum contains natural antibodies (nAb), predominantly of the IgM and IgG3 subclasses, with markedly greater binding to rat bone marrow cells (BMC) than to rat splenocytes or thymocytes. Since much greater numbers of rat BMC than of allogeneic murine BMC are required to achieve engraftment in mice, we considered the possibility that these nAbs might be responsible, and that the increased numbers of BMC might be required to absorb these nAb. To evaluate the effect of these nAb on engraftment of rat BMC in mice, we have now performed adoptive transfer studies using T and B cell-deficient severe combined immunodeficiency disease (SCID) mice as recipients. Administration of as few as 5 x 10(5) T cell-depleted rat BMC led to induction of stable xenochimerism in SCID mice conditioned with 4-Gy whole body irradiation. Rat T cells developed after a delay of several weeks, and conferred the ability to reject non-donor-type rat skin grafts, whereas donor-type grafts were accepted. Adoptive transfer of 4 ml of normal BALB/c serum led to a marked reduction in the level of rat chimerism in SCID recipients of 2 x 10(6) F344 BMC. The ability of sera to inhibit engraftment of rat BMC correlated with their cytotoxic nAb content, and the inhibitory effect of highly cytotoxic sera could be overcome by administration of large numbers of rat BMC. Thus, normal mouse serum has a limited ability to hinder engraftment of rat BMC, and this degree of resistance can be overcome by adsorption when large numbers of BMC are administered. Eliminating nAb from serum may be more difficult in discordant species combinations in recipients with functional B cells, but may likewise permit the use of BMT as a means of inducing transplantation tolerance. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SURG SERV,TRANSPLANTAT BIOL RES CTR,MGH-E,BLDG 149,BOSTON,MA 02129. NCI,IMMUNOL BRANCH,BETHESDA,MD 20892. NR 42 TC 36 Z9 36 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 DEC 15 PY 1991 VL 147 IS 12 BP 4140 EP 4146 PG 7 WC Immunology SC Immunology GA GW031 UT WOS:A1991GW03100014 PM 1753089 ER PT J AU GASPARI, AA KATZ, SI AF GASPARI, AA KATZ, SI TI INDUCTION OF INVIVO HYPORESPONSIVENESS TO CONTACT ALLERGENS BY HAPTEN-MODIFIED IA+-KERATINOCYTES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTIGEN-PRESENTING CAPACITY; MODIFIED LYMPHOID-CELLS; HLA-DR EXPRESSION; LANGERHANS CELLS; SYSTEMIC SUPPRESSION; TOLERANCE INDUCTION; EPIDERMAL-CELLS; UVB RADIATION; HOST DISEASE; HYPERSENSITIVITY AB Because our previous in vitro studies of hapten-modified Ia+ keratinocytes (KC) indicated that these cells induced anergy in Ag-specific Th1 cells, we assayed such cells for their ability to induce unresponsiveness in an in vivo animal model system of delayed type hypersensitivity (allergic contact dermatitis). Naive animals that were treated with i.p. injections of FITC-modified Ia+ cultured Langerhans cells (cLC) developed allergic contact dermatitis to subsequent hapten challenge; whereas, animals treated with similar doses of FITC-Ia+ KC failed to become sensitized to epicutaneous application of FITC, as evidenced by absent ear swelling responses to a FITC challenge. Those animals that were first treated with intraperitoneal injections of hapten modified Ia+ KC could not be sensitized when they were subsequently exposed to sensitizing doses of FITC; whereas a similar first exposure to FITC-cultured Langerhans cells did not interfere with epicutaneous sensitization. This hyporesponsiveness to sensitization was hapten specific, as FITC-Ia+ KC-treated animals were hyporesponsive only to FITC but not to the irrelevant hapten, TNCB. Additionally, Ia- KC failed to induce unresponsiveness. Additional studies indicate that the hyporesponsiveness was not passively transferrable with splenocytes and was not related to the I-J MHC locus. In contrast to our in vitro studies, the unresponsiveness induced by hapten-modified Ia+ KC in vivo was transient in nature. These data indicate that hapten-modified Ia+ KC function in vivo as nonstimulatory accessory cells, by generating down-regulatory signals that can interfere with the induction of contact hypersensitivity. C1 UNIV ROCHESTER,SCH MED & DENT,DEPT DERMATOL,ROCHESTER,NY 14642. NCI,DERMATOL BRANCH,BALTIMORE,MD 21211. NR 33 TC 44 Z9 46 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 DEC 15 PY 1991 VL 147 IS 12 BP 4155 EP 4161 PG 7 WC Immunology SC Immunology GA GW031 UT WOS:A1991GW03100016 PM 1753091 ER PT J AU MOROZUMI, T UETSUKA, H KOMIYAMA, M PITHA, J AF MOROZUMI, T UETSUKA, H KOMIYAMA, M PITHA, J TI SELECTIVE SYNTHESIS USING CYCLODEXTRINS AS CATALYSTS .6. CYCLODEXTRIN MODIFICATION FOR PARA-SELECTIVE HYDROXYMETHYLATION AND HYDROXYETHYLATION OF PHENOL SO JOURNAL OF MOLECULAR CATALYSIS LA English DT Article ID BETA-CYCLODEXTRIN; FORMALDEHYDE AB 4-(Hydroxymethyl)phenol is selectively synthesized from phenol and formaldehyde by use of beta-cyclodextrins (beta-CyDs) carrying quaternary ammonium, glucose and maltose residues as catalysts. The chemical modification of beta-CyD largely promotes the catalytic activity, especially the rate-accelerating effect. Yield of the desired para-substituted product (16.8 mol%) for the beta-CyD having the quaternary ammonium substituent (0.3 M) is 7.3 times as large as that (2.3 mol%) for unmodified beta-CyD (the selectivities are 80 and 79%, respectively). Selective synthesis of 4-(hydroxyethyl)phenol from phenol and acetaldehyde is successfully achieved also by use of the beta-CyD derivatives having sugar branches, which is in marked contrast with the marginal activity of unmodified beta-CyD. C1 UNIV TSUKUBA,INST MAT SCI,TSUKUBA,IBARAKI 305,JAPAN. NIA,GRC,BALTIMORE,MD 21224. NR 14 TC 8 Z9 8 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-5102 J9 J MOL CATAL PD DEC 15 PY 1991 VL 70 IS 3 BP 399 EP 406 DI 10.1016/0304-5102(91)80135-P PG 8 WC Chemistry, Physical SC Chemistry GA GZ266 UT WOS:A1991GZ26600012 ER PT J AU TEO, KK YUSUF, S COLLINS, R HELD, PH PETO, R AF TEO, KK YUSUF, S COLLINS, R HELD, PH PETO, R TI EFFECTS OF INTRAVENOUS MAGNESIUM IN SUSPECTED ACUTE MYOCARDIAL-INFARCTION - OVERVIEW OF RANDOMIZED TRIALS SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Article ID SYSTEMATIC OVERVIEWS; ARRHYTHMIAS; SULFATE; HEART; DEATH; NEED AB Objective - To investigate the effect of intravenous magnesium on mortality in suspected acute myocardial infarction. Design - Systematic overview of all available randomised trials in which patients were allocated to receive either intravenous magnesium or otherwise similar treatment without magnesium. Setting - Coronary care units of several hospitals. Patients - 1301 patients in seven randomised trials. Main outcome measure - Short term mortality. Results - Considering the seven trials collectively there were 25 (3.8%) deaths among 657 patients allocated to receive magnesium and 53 (8.2%) deaths among 644 patients allocated control, generally during hospital follow up. This represents a 55% reduction in the odds of death (p < 0.001) with 95% confidence intervals ranging from about one third to about two thirds. 70 of 648 patients allocated magnesium compared with 109 of 641 controls had serious ventricular arrhythmias, suggesting that magnesium reduces the incidence, though the definition varied among trials. Other adverse effects were rare in the limited number of patients for whom this data were available. Conclusion - Despite the limited number of patients randomised this overview suggests that intravenous magnesium therapy may reduce mortality in patients with acute myocardial infarction. Further large scale trials to confirm (or refute) these findings are desirable. C1 NHLBI, DIV EPIDEMIOL & CLIN APPLICAT, CLIN TRIALS BRANCH, BETHESDA, MD 20892 USA. UNIV OXFORD, CLIN TRIALS SERV, OXFORD, ENGLAND. RP YUSUF, S (reprint author), NHLBI, DIV EPIDEMIOL & CLIN APPLICAT, CLIN TRIALS BRANCH, BETHESDA, MD 20892 USA. NR 42 TC 246 Z9 254 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BMJ-BRIT MED J JI BMJ-British Medical Journal PD DEC 14 PY 1991 VL 303 IS 6816 BP 1499 EP 1503 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA GV476 UT WOS:A1991GV47600018 PM 1838289 ER PT J AU GOEDERT, JJ DULIEGE, AM AMOS, CI FELTON, S BIGGAR, RJ AF GOEDERT, JJ DULIEGE, AM AMOS, CI FELTON, S BIGGAR, RJ TI HIGH-RISK OF HIV-1 INFECTION FOR 1ST-BORN TWINS SO LANCET LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ONE DIZYGOTIC TWIN; CARRIER MOTHERS; INFANTS BORN; TRANSMISSION; TYPE-1 AB To examine the epidemiology and natural history of mother-to-infant transmission of human immunodeficiency virus type 1 (HIV-1), especially genetic and intrapartum exposure factors, we obtained data on twins and triplets born to women infected with the virus. 40 investigators in nine countries contributed demographic, clinical, and epidemiological data on 100 sets of twins and 1 set of triplets. Among the 66 evaluable sets, HIV-1 infection was more common in first-born than in second- born twins (p = 0.004). In 22 sets, only one twin was infected (18 first-born, 4 second-born). 50% of first-born twins delivered vaginally and 38% of first-born twins delivered by caesarean were infected, compared with 19% of second-born twins delivered by either route. HIV-1 infection status tended to be concordant in more monozygotic (14 of 17 sets) than dizygotic (26 of 43) sets, but the frequency and clinical signs of HIV-1-related disease were similar in only 3 of the 10 sets with both children infected. These findings suggest that some infants may be infected in utero before labour but that a substantial proportion of HIV-1 transmission occurs as the first twin encounters the cervix and birth canal. Such measures as cleansing of the birth canal and caesarean delivery before membrane rupture might reduce the risk of transmission for infants born to HIV-1-infected women and should be the subjects of controlled clinical trials. Caesarean section should not be regarded as a wholly preventive measure, however, since substantial proportions of both first-born and second-born twins delivered in this way were infected. C1 GENENTECH INC,DIV CLIN RES,SAN FRANCISCO,CA 94080. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NCI,VIRAL EPIDEMIOL SECT,ROCKVILLE,MD. NCI,FAMILY STUDIES SECT,ROCKVILLE,MD. RP GOEDERT, JJ (reprint author), 6130 EXECUT BLVD,SUITE 434,ROCKVILLE,MD 20852, USA. FU NCI NIH HHS [N01-CP-95612] NR 30 TC 271 Z9 273 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD DEC 14 PY 1991 VL 338 IS 8781 BP 1471 EP 1475 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA GV077 UT WOS:A1991GV07700001 PM 1683916 ER PT J AU RICAURTE, GA MOLLIVER, ME MARTELLO, MB KATZ, JL WILSON, MA MARTELLO, AL AF RICAURTE, GA MOLLIVER, ME MARTELLO, MB KATZ, JL WILSON, MA MARTELLO, AL TI DEXFENFLURAMINE NEUROTOXICITY IN BRAINS OF NONHUMAN-PRIMATES SO LANCET LA English DT Note ID RAT-BRAIN; FENFLURAMINE AB Dexfenfluramine, a drug prescribed for appetite suppression, was evaluated in non-human primates for its potential to produce toxic effects on brain serotonin (5-HT) neurons. Squirrel monkeys received dexfenfluramine subcutaneously twice daily for four days at doses of 1.25 or 5.00 mg/kg. Two weeks later, a dose-related depletion of 5-HT and 5-hydroxyindoleacetic acid was found, together with a reduced number of 5-HT uptake sites. Morphological studies showed acute pathological changes in 5-HT axons, followed by a persistent decrease in 5-HT axon density. Our findings indicate that dexfenfluramine damages central 5-HT neurons in monkeys and raise concern about the potential neurotoxicity of this drug in man. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. NIDA,ADDICT RES CTR,BALTIMORE,MD. RP RICAURTE, GA (reprint author), JOHNS HOPKINS UNIV,FRANCIS SCOTT KEY MED CTR,SCH MED,DEPT NEUROL,301 BAYVIEW BLVD,BALTIMORE,MD 21224, USA. OI Katz, Jonathan/0000-0002-1068-1159 FU NIDA NIH HHS [DA04431, DA05707] NR 10 TC 75 Z9 75 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 DEC 14 PY 1991 VL 338 IS 8781 BP 1487 EP 1488 DI 10.1016/0140-6736(91)92301-H PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA GV077 UT WOS:A1991GV07700005 PM 1720853 ER PT J AU ZHANG, K PAPAGEORGE, AG MARTIN, P VASS, WC OLAH, Z POLAKIS, PG MCCORMICK, F LOWY, DR AF ZHANG, K PAPAGEORGE, AG MARTIN, P VASS, WC OLAH, Z POLAKIS, PG MCCORMICK, F LOWY, DR TI HETEROGENEOUS AMINO-ACIDS IN RAS AND RAP1A SPECIFYING SENSITIVITY TO GAP PROTEINS SO SCIENCE LA English DT Article ID GTPASE-ACTIVATING PROTEIN; GENE-PRODUCT; CATALYTIC DOMAIN; EFFECTOR DOMAIN; RAS-P21 GTPASE; P21; IDENTIFICATION; MUTANTS; PURIFICATION; STIMULATION AB Guanosine triphosphatase (GTPase) activity of Ras is increased by interaction with Ras-GAP (GTPase-activating protein) or with the GAP-related domain of the type 1 neurofibromatosis protein (NF1-GRD), but Ras is not affected by interaction with cytoplasmic and membrane forms of Rap-GAP; Rap1A, whose effector function can suppress transformation by Ras, is sensitive to both forms of Rap-GAP and resistant to Ras-GAP and NF1-GRD. A series of chimeric proteins composed of portions of Ras and Rap were constructed; some were sensitive to Ras-GAP but resistant to NF1-GRD, and others were sensitive to cytoplasmic Rap-GAP but resistant to membrane Rap-GAP. Sensitivity of chimeras to Ras-GAP and cytoplasmic Rap-GAP was mediated by amino acids that are carboxyl-terminal to the effector region. Residues 61 to 65 of Ras conferred Ras-GAP sensitivity, but a larger number of Rap1A residues were required for sensitivity to cytoplasmic Rap-GAP. Chimeras carrying the Ras effector region that were sensitive only to Ras-GAP or only to cytoplasmic Rap-GAP transformed NIH 3T3 cells poorly. Thus, distinct amino acids of Ras and Rap1A mediate sensitivity to each of the proteins with GAP activity, and transforming potential of Ras and sensitivity of Ras to Ras-GAP are at least partially independent properties. C1 CETUS CORP,EMERYVILLE,CA 94608. RP ZHANG, K (reprint author), NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892, USA. NR 43 TC 36 Z9 38 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 13 PY 1991 VL 254 IS 5038 BP 1630 EP 1634 DI 10.1126/science.1749934 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GV073 UT WOS:A1991GV07300041 PM 1749934 ER PT J AU EDDY, EM OBRIEN, DA FENDERSON, BA WELCH, JE AF EDDY, EM OBRIEN, DA FENDERSON, BA WELCH, JE TI INTERMEDIATE FILAMENT-LIKE PROTEINS IN THE FIBROUS SHEATH OF THE MOUSE SPERM FLAGELLUM SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID RESOLUTION 2-DIMENSIONAL ELECTROPHORESIS; ISOLATED SPERMATOGENIC CELLS; SERTOLI CELLS; MAMMALIAN SPERMATOZOA; RAT SPERMATOZOA; VIMENTIN-TYPE; SPERMIOGENESIS; PERFORATORIUM; COMPONENTS; EXPRESSION C1 UNIV N CAROLINA,DEPT PEDIAT,CHAPEL HILL,NC 27995. THOMAS JEFFERSON UNIV,DEPT PATHOL,PHILADELPHIA,PA 19107. UNIV N CAROLINA,REPROD BIOL LABS,CHAPEL HILL,NC 27995. UNIV N CAROLINA,DEPT CELL BIOL & ANAT,CHAPEL HILL,NC 27995. RP EDDY, EM (reprint author), NIEHS,REPROD & DEV TOXICOL LAB,GAMETE BIOL SECT,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 41 TC 29 Z9 30 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD DEC 12 PY 1991 VL 637 BP 224 EP 239 DI 10.1111/j.1749-6632.1991.tb27312.x PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM208 UT WOS:A1991JM20800016 PM 1723852 ER PT J AU OBRIEN, DA GABEL, CA WELCH, JE EDDY, EM AF OBRIEN, DA GABEL, CA WELCH, JE EDDY, EM TI MANNOSE 6-PHOSPHATE RECEPTORS - POTENTIAL MEDIATORS OF GERM CELL-SERTOLI CELL-INTERACTIONS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Review ID GROWTH FACTOR-II; MESSENGER RIBONUCLEIC-ACID; ANDROGEN-BINDING-PROTEIN; TUBULAR BASOLATERAL MEMBRANES; TESTICULAR PERITUBULAR CELLS; FOLLICLE-STIMULATING HORMONE; FACTOR-BETA; SPERMATOGENIC CELLS; SEMINIFEROUS EPITHELIUM; LYSOSOMAL-ENZYMES C1 PFIZER INC,CENT RES,DEPT IMMUNOL & INFECT DIS,GROTON,CT 06340. NIEHS,REPROD & DEV TOXICOL LAB,GAMETE BIOL SECT,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,DEPT PEDIAT,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT CELL BIOL & ANAT,CHAPEL HILL,NC 27599. RP OBRIEN, DA (reprint author), UNIV N CAROLINA,REPROD BIOL LABS,CHAPEL HILL,NC 27599, USA. FU NICHD NIH HHS [R01 HD026485, HD26485] NR 113 TC 14 Z9 14 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD DEC 12 PY 1991 VL 637 BP 327 EP 339 DI 10.1111/j.1749-6632.1991.tb27320.x PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM208 UT WOS:A1991JM20800024 PM 1664679 ER PT J AU STROMBERG, C TSUTSUMI, K VISWANATHAN, M SAAVEDRA, JM AF STROMBERG, C TSUTSUMI, K VISWANATHAN, M SAAVEDRA, JM TI ANGIOTENSIN-II AT1 RECEPTORS IN RAT SUPERIOR CERVICAL-GANGLIA - CHARACTERIZATION AND STIMULATION OF PHOSPHOINOSITIDE HYDROLYSIS SO EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION LA English DT Article DE ANGIOTENSIN RECEPTOR; SYMPATHETIC GANGLIA; AUTORADIOGRAPHY; GUANINE NUCLEOTIDES; INOSITOL PHOSPHATES; ANGIOTENSIN RECEPTOR ANTAGONIST ID ADRENERGIC NERVE-ENDINGS; BINDING-SITES; ADRENAL-MEDULLA; BRAIN; SUBTYPES; SYSTEM; AUTORADIOGRAPHY; FACILITATION; CELLS AB Angiotensin II receptor number was higher in superior cervical ganglia of 2-week-old when compared to 8-week-old rats. In both young and adult rats, specific binding of [I-125][Sar1]angiotensin II was displaced competitively by the AT1-receptor antagonist DuP 753 but not by the AT2-receptor competitor PD 123177. In ganglia from adult rats, DuP 753 competed with an IC50 of 113 nM. The stable guanine nucleotide GTP-gamma-S inhibited binding of [I-125][Sar1]angiotensin II in young and adult rats by approximately 50% with IC50 values of 105 and 120 nM, respectively, suggesting that the angiotensin receptor is G-protein linked. Angiotensin II at a dose of 1-mu-M stimulated inositol phosphate formation 58% over control values in superior cervical ganglia from 8-week-old rats. This effect was totally blocked by 10-mu-M DuP 753 but not by 10-mu-M PD 123177. Our findings demonstrate that rat superior cervical ganglia contain AT1-type angiotensin receptors that are probably G-protein linked, and their stimulation results in increased inositol phospholipid metabolism. RP STROMBERG, C (reprint author), NIMH,PHARMACOL SECT,CLIN SCI LAB,9000 ROCKVILLE PIKE,BLDG 10,ROOM 2D 45,BETHESDA,MD 20892, USA. NR 36 TC 33 Z9 33 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0922-4106 J9 EUR J PHARM-MOLEC PH JI Eur. J. Pharmacol.-Molec. Pharmacol. Sect. PD DEC 12 PY 1991 VL 208 IS 4 BP 331 EP 336 DI 10.1016/0922-4106(91)90079-W PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GW802 UT WOS:A1991GW80200007 PM 1667760 ER PT J AU MONTEFIORI, DC HIRSCH, VM JOHNSON, PR AF MONTEFIORI, DC HIRSCH, VM JOHNSON, PR TI AIDS RESPONSE SO NATURE LA English DT Letter C1 NIAID,INFECT DIS LAB,ROCKVILLE,MD 20852. OHIO STATE UNIV,DEPT PEDIAT,COLUMBUS,OH 43205. RP MONTEFIORI, DC (reprint author), VANDERBILT UNIV,MED CTR,SCH MED,DEPT PATHOL,NASHVILLE,TN 37232, USA. RI Johnson, Philip/A-6892-2009 NR 5 TC 7 Z9 7 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD DEC 12 PY 1991 VL 354 IS 6353 BP 439 EP 440 DI 10.1038/354439c0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GV078 UT WOS:A1991GV07800043 ER PT J AU KAWABATA, S HIGGINS, GA GORDON, JW AF KAWABATA, S HIGGINS, GA GORDON, JW TI AMYLOID PLAQUES, NEUROFIBRILLARY TANGLES AND NEURONAL LOSS IN BRAINS OF TRANSGENIC MICE OVEREXPRESSING A C-TERMINAL FRAGMENT OF HUMAN AMYLOID PRECURSOR PROTEIN (RETRACTED ARTICLE. SEE VOL 356, PG 265, 1992) SO NATURE LA English DT Article; Retracted Publication ID ALZHEIMERS-DISEASE; DIFFERENTIAL REGULATION; GENE-EXPRESSION; DOWNS-SYNDROME; MOUSE EMBRYOS; THY-1 GENE; DNA; INJECTION; RECEPTOR AB ALZHEIMER's disease (AD) affects more than 30% of people over 80 years of age 1,2. The aetiology and pathogenesis of this progressive dementia is poorly understood, but symptomatic disease is associated histopathologically with amyloid plaques, neurofibrillary tangles and neuronal loss primarily in the temporal lobe and neocortex of the brain. The core of the extracellular plaque is a derivative of the amyloid precursor protein (App) 3, referred to as beta/A4 (refs 4-6), and contains the amino-acid residues 29-42 that are normally embedded in the membrane-spanning region of the precursor 3. The cellular source of APP and the relationship of its deposition to the neuropathology of AD is unknown. To investigate the relationship between APP overexpression and amyloidogenesis, we have developed a vector to drive expression specifically in neurons of a C-terminal fragment of APP that contains the beta/A4 region, and have used a transgenic mouse system 7,8 to insert and express this construct. We report here that overexpression of this APP transgene in neurons is sufficient to produce extracellular dense-core amyloid plaques, neurofibrillary tangles and neuronal degeneration similar to that in the AD brain. C1 MT SINAI MED CTR, DEPT GERIATR & ADULT DEV, 2056 ANNENBERG, NEW YORK, NY 10029 USA. MT SINAI MED CTR, DEPT OBSTET GYNECOL & REPROD SCI, NEW YORK, NY 10029 USA. YAMANOUCHI PHARMACEUT CO LTD, TOKYO 103, JAPAN. NIA, GERONTOL RES CTR, BALTIMORE, MD 21224 USA. RP GORDON, JW (reprint author), MT SINAI MED CTR, DEPT GERIATR & ADULT DEV, 2056 ANNENBERG, NEW YORK, NY 10029 USA. NR 30 TC 83 Z9 85 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 12 PY 1991 VL 354 IS 6353 BP 476 EP 478 DI 10.1038/354476a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GV078 UT WOS:A1991GV07800059 PM 1793460 ER PT J AU SMEAL, T BINETRUY, B MERCOLA, DA BIRRER, M KARIN, M AF SMEAL, T BINETRUY, B MERCOLA, DA BIRRER, M KARIN, M TI ONCOGENIC AND TRANSCRIPTIONAL COOPERATION WITH HA-RAS REQUIRES PHOSPHORYLATION OF C-JUN ON SERINE-63 AND SERINE-73 SO NATURE LA English DT Article ID EXPRESSION; GENE; PEA1 AB RECENT advances indicate a link between tumour promoters, transformation, and AP-1 activity 1. Protein kinase C activation increases AP-1 DNA-binding activity independently of new protein synthesis 2,3. AP-1 is also stimulated by transforming oncoproteins and growth factors 4-6. These proteins are thought to participate in a signalling cascade affecting the nuclear AP-1 complex composed of the Jun and Fos proteins 1,7,8. Because c-Jun is the most potent transactivator in the AP-1 complex 9-12 and is elevated in Ha-ras-transformed cells, in which c-Fos is downregulated 13,14, we focused on it as a potential target. c-Jun could convert input from an oncogenic signalling cascade into changes in gene expression. Indeed, transformation of rat embryo fibroblasts by c-Jun requires an intact transcriptional activation domain 15 and cooperation with oncogenic Ha-ras 16. Expression of oncogenic Ha-ras augments transactivation by c-Jun and stimulates its phosphorylation 14. Here we describe the mapping of the Ha-ras-responsive phosphorylation sites to serines 63 and 73 of c-Jun. Site-directed mutagenesis indicates that phosphorylation of these serines is essential for stimulation of c-Jun activity and for cooperation with Ha-ras in ocogenic transformation. C1 UNIV CALIF SAN DIEGO,SCH MED,CTR MOLEC GENET,DEPT PHARMACOL,LA JOLLA,CA 92093. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20814. UNIV CALIF SAN DIEGO,SCH MED,CTR MOLEC GENET,DEPT PATHOL,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,SCH MED,CTR MOLEC GENET,DEPT BIOL,LA JOLLA,CA 92093. RP KARIN, M (reprint author), UNIV CALIF SAN DIEGO,SCH MED,CTR MOLEC GENET,DEPT PHARMACOL,LA JOLLA,CA 92093, USA. RI Binetruy, Bernard/A-6465-2009 NR 26 TC 728 Z9 729 U1 2 U2 8 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD DEC 12 PY 1991 VL 354 IS 6353 BP 494 EP 496 DI 10.1038/354494a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GV078 UT WOS:A1991GV07800065 PM 1749429 ER PT J AU WEINSTEIN, LS SHENKER, A GEJMAN, PV MERINO, MJ FRIEDMAN, E SPIEGEL, AM AF WEINSTEIN, LS SHENKER, A GEJMAN, PV MERINO, MJ FRIEDMAN, E SPIEGEL, AM TI ACTIVATING MUTATIONS OF THE STIMULATORY G-PROTEIN IN THE MCCUNE-ALBRIGHT SYNDROME SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HUMAN PITUITARY-TUMORS; HEREDITARY OSTEODYSTROPHY; ADENYLYL CYCLASE; CUSHING SYNDROME; ALPHA; GENE; DNA; POLYMERASE; CHAIN; ALTER AB Background. The McCune-Albright syndrome is a sporadic disease characterized by polyostotic fibrous dysplasia, cafe au lait spots, sexual precocity, and hyperfunction of multiple endocrine glands. These manifestations may be explained by a somatic mutation in affected tissues that results in activation of the signal-transduction pathway generating cyclic AMP (cAMP). We analyzed DNA from tissues of patients with the McCune-Albright syndrome for the presence of activating mutations of the gene for the a subunit of the G protein (G(s)alpha) that stimulates cAMP formation. Methods. Genomic DNA fragments encompassing regions (exons 8 and 9) previously found to contain activating missense mutations of the G(s)alpha gene (gsp mutations) in sporadically occurring pituitary tumors were amplified in tissues from four patients with the McCune-Albright syndrome by the polymerase chain reaction. The amplified DNA was analyzed for mutations by denaturing gradient gel electrophoresis and allele-specific oligonucleotide hybridization. Results. We detected one of two activating mutations within exon 8 of the G(s)alpha gene in tissues from all four patients, including affected endocrine organs (gonads, adrenal glands, thyroid, and pituitary) and tissues not classically involved in the McCune-Albright syndrome. In two of the patients histidine was substituted for arginine at position 201 of G(s)alpha, and in the other two patients cysteine was substituted for the same arginine residue. In each patient the proportion of cells affected varied from tissue to tissue. In two endocrine organs, the highest proportion of mutant alleles was found in regions of abnormal cell proliferation. Conclusions. Mutations within exon 8 of the G(s)alpha gene that result in increased activity of the Gs protein and increased cAMP formation are present in various tissues of patients with the McCune-Albright syndrome. Somatic mutation of this gene early in embryogenesis could result in the mosaic population of normal and mutant-bearing tissues that may underlie the clinical manifestations of this disease. C1 NIMH, CLIN NEUROGENET BRANCH, BETHESDA, MD 20892 USA. NCI, PATHOL LAB, BETHESDA, MD 20892 USA. RP WEINSTEIN, LS (reprint author), NIDDK, MOLEC PATHOPHYSIOL BRANCH, BLDG 10, RM 8D-17, BETHESDA, MD 20892 USA. OI Weinstein, Lee/0000-0002-1899-5152 NR 45 TC 945 Z9 973 U1 2 U2 9 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 12 PY 1991 VL 325 IS 24 BP 1688 EP 1695 DI 10.1056/NEJM199112123252403 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA GU418 UT WOS:A1991GU41800003 PM 1944469 ER PT J AU PIERCE, JP GILPIN, E BURNS, DM WHALEN, E ROSBROOK, B SHOPLAND, D JOHNSON, M AF PIERCE, JP GILPIN, E BURNS, DM WHALEN, E ROSBROOK, B SHOPLAND, D JOHNSON, M TI DOES TOBACCO ADVERTISING TARGET YOUNG-PEOPLE TO START SMOKING - EVIDENCE FROM CALIFORNIA SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID UNITED-STATES; CIGARETTE-SMOKING; TRENDS AB Objective. - To evaluate whether tobacco advertising encourages teenagers younger than 18 years to start smoking. Design. - Comparison of 1990 California telephone survey data with data from a 1986 national telephone survey (both used a random-digit dialing system); 95% confidence intervals were calculated. To test our hypothesis, we considered whether the perception of advertising was related to age, whether the pattern of market share across age and sex groups followed the pattern of perceived advertising, and whether changes in market share paralleled changes in advertising as perceived by the youngest age group. Participants. - There were 24296 adults and 5040 teenagers. Results. - The most advertised brands of cigarettes were Marlboro, according to 33.6% of adults and 41.8% of teenagers, and Camel, according to 13.7% of adults and 28.5% of teenagers-named most often by 12- to 13-year-olds (34.2%). The brands that were purchased most often were Marlboro and Camel. Together these were the brands of choice of 79.9% of males and 85% of females aged 12 through 17 years. Marlboro's market share increased in youths and young adults up to age 24 years and then decreased gradually with age; Camel's market share decreased abruptly with age: it was the brand of choice of 24.5% +/- 5.8% of males aged 12 through 17 years but was chosen by only 12.7% +/- 3.6% of males aged 18 through 24 years; for females, 21.7% +/- 13.7% aged 12 through 17 years chose Camels, while only 5.5% +/- 3.2% aged 18 through 24 years preferred this brand. Both Marlboro and Camel brands had a higher market share in California in 1990 compared with that for the United States in 1986. Of interest is that the market share for Camel increased among the younger smokers but was more evenly distributed for Marlboro. Conclusions. - Perception of advertising is higher among young smokers; market-share patterns across age and sex groups follow the perceived advertising patterns; and changes in market share resulting from advertising occur mainly in younger smokers. Cigarette advertising encourages youth to smoke and should be banned. C1 CALIF DEPT HLTH SERV,TOBACCO CONTROL SECT,SACRAMENTO,CA. NCI,BETHESDA,MD 20892. RP PIERCE, JP (reprint author), UNIV CALIF SAN DIEGO,POPULAT STUDIES CANC PREVENT,2251 SAN DIEGO AVE,SUITE B-111,SAN DIEGO,CA 92110, USA. NR 26 TC 186 Z9 187 U1 2 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 11 PY 1991 VL 266 IS 22 BP 3154 EP 3158 DI 10.1001/jama.266.22.3154 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA GT654 UT WOS:A1991GT65400024 PM 1956103 ER PT J AU MANLEY, M EPPS, RP HUSTEN, C GLYNN, T SHOPLAND, D AF MANLEY, M EPPS, RP HUSTEN, C GLYNN, T SHOPLAND, D TI CLINICAL INTERVENTIONS IN TOBACCO CONTROL - A NATIONAL-CANCER-INSTITUTE TRAINING-PROGRAM FOR PHYSICIANS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SMOKING CESSATION; RANDOMIZED TRIAL; SMOKERS; QUIT RP MANLEY, M (reprint author), NCI,DIV CANC PREVENT & CONTROL,CANC CONTROL SCI PROGRAM,EPN-241,BALTIMORE,MD 21211, USA. NR 12 TC 64 Z9 66 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 11 PY 1991 VL 266 IS 22 BP 3172 EP 3173 DI 10.1001/jama.266.22.3172 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA GT654 UT WOS:A1991GT65400028 PM 1956107 ER PT J AU LAFYATIS, R DENHEZ, F WILLIAMS, T SPORN, M ROBERTS, A AF LAFYATIS, R DENHEZ, F WILLIAMS, T SPORN, M ROBERTS, A TI SEQUENCE SPECIFIC PROTEIN-BINDING TO AND ACTIVATION OF THE TGF-BETA-3 PROMOTER THROUGH A REPEATED TCCC MOTIF SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GROWTH FACTOR-BETA; COMPLEMENTARY-DNA; DIFFERENTIAL EXPRESSION; ADULT TISSUES; GENE FAMILY; TRANSCRIPTION; FACTOR-BETA-3; PRECURSOR; ELEMENTS; CLONING AB We have previously characterized the TGF-beta-3 promoter and shown that the activity of this promoter is highly variable in different cell types. Although the promoter contains a proximal cAMP responsive element, which is critical to basal and forskolin-induced promoter activity, this element is not responsible for the variable, cell-specific regulation of the promoter. In this paper, we identify a 25 base pair sequence in the proximal region of the TGF-beta-3 promoter that binds a novel DNA-binding protein. This region includes the sequence T-CCCTCCCTCCC, (3 x TCCC), and mutation of these TCCC repeats inhibits protein binding. Further, we show that in the cell line A375, which we have previously shown expresses high levels of TGF-beta-3 mRNA, this region is responsible for mediating high level TGF-beta-3 promoter activity. Immediately 3' to the 3 x TCCC sequence is a consensus AP-2 binding site, however, we show that this region does not bind AP-2, and AP-2 does not transactivate the TGF-beta-3 promoter. Therefore, we provide strong evidence that high level expression of TGF-beta-3 in A375 cells results from transactivation of the TGF-beta-3 promoter by a protein that binds to a repeated TCCC motif in the promoter and suggest that this DNA-binding protein likely also regulates aspects of developmental and tissue-specific expression of this cytokine C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. UNIV CALIF BERKELEY,DEPT BIOCHEM,BERKELEY,CA 94720. NR 21 TC 33 Z9 33 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC 11 PY 1991 VL 19 IS 23 BP 6419 EP 6425 DI 10.1093/nar/19.23.6419 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GV816 UT WOS:A1991GV81600009 PM 1754378 ER PT J AU WOODFORD, K USDIN, K AF WOODFORD, K USDIN, K TI TURBOPREP DNA - ULTRAQUICK PREPARATION OF PLASMID DNA FROM SINGLE COLONIES FOR DNA SEQUENCING SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 NIDKD,BIOL PHARMACOL LAB,GENOM STRUCT & FUNCT SECT,BETHESDA,MD 20892. NR 2 TC 8 Z9 9 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 DEC 11 PY 1991 VL 19 IS 23 BP 6652 EP 6652 DI 10.1093/nar/19.23.6652 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GV816 UT WOS:A1991GV81600054 PM 1754410 ER PT J AU LATIF, F TORY, K GEIL, L ZBAR, B LERMAN, MI AF LATIF, F TORY, K GEIL, L ZBAR, B LERMAN, MI TI A NEW DNA MARKER, D3S740, IDENTIFIES A MSPI POLYMORPHISM ON CHROMOSOME-3P SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,BLDG 560,ROOM 12-71,FREDERICK,MD 21701. FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21701. NR 1 TC 0 Z9 0 U1 0 U2 12 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 DEC 11 PY 1991 VL 19 IS 23 BP 6658 EP 6658 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GV816 UT WOS:A1991GV81600060 PM 1721706 ER PT J AU LATIF, F TORY, K GEIL, L ZBAR, B LERMAN, MI AF LATIF, F TORY, K GEIL, L ZBAR, B LERMAN, MI TI A NEW DNA MARKER, D3S754, IDENTIFIES A HINDIII POLYMORPHISM ON CHROMOSOME-3P SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,BLDG 560,ROOM 12-71,FREDERICK,MD 21701. FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21701. NR 1 TC 0 Z9 0 U1 0 U2 12 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 DEC 11 PY 1991 VL 19 IS 23 BP 6658 EP 6658 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GV816 UT WOS:A1991GV81600061 PM 1721706 ER PT J AU LATIF, F TORY, K GEIL, L ZBAR, B LERMAN, MI AF LATIF, F TORY, K GEIL, L ZBAR, B LERMAN, MI TI A NEW DNA MARKER, D3S742, IDENTIFIES A MSPI AND A TAQI POLYMORPHISM ON CHROMOSOME-3P SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,BLDG 560,ROOM 12-71,FREDERICK,MD 21701. FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21701. NR 1 TC 0 Z9 0 U1 0 U2 11 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 DEC 11 PY 1991 VL 19 IS 23 BP 6659 EP 6659 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GV816 UT WOS:A1991GV81600063 PM 1684422 ER PT J AU LATIF, F TORY, K GEIL, L ZBAR, B LERMAN, MI AF LATIF, F TORY, K GEIL, L ZBAR, B LERMAN, MI TI A NEW DNA MARKER, D3S733, IDENTIFIES A HINDIII POLYMORPHISM ON CHROMOSOME-3P SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,BLDG 560,ROOM 12-71,FREDERICK,MD 21701. FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21701. NR 1 TC 0 Z9 0 U1 0 U2 11 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 DEC 11 PY 1991 VL 19 IS 23 BP 6659 EP 6659 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GV816 UT WOS:A1991GV81600062 PM 1684422 ER PT J AU LATIF, F TORY, K GEIL, L ZBAR, B LERMAN, MI AF LATIF, F TORY, K GEIL, L ZBAR, B LERMAN, MI TI A NEW DNA MARKER, D3S743, IDENTIFIES A MSPI POLYMORPHISM ON CHROMOSOME-3P SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,BLDG 560,ROOM 12-71,FREDERICK,MD 21701. FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21701. NR 1 TC 0 Z9 0 U1 0 U2 10 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 DEC 11 PY 1991 VL 19 IS 23 BP 6660 EP 6660 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GV816 UT WOS:A1991GV81600064 PM 1721708 ER PT J AU LATIF, F TORY, K GEIL, L ZBAR, B LERMAN, MI AF LATIF, F TORY, K GEIL, L ZBAR, B LERMAN, MI TI A NEW DNA MARKER, D3S640, IDENTIFIES A DRAI, HINDIII AND TAQI POLYMORPHISMS ON CHROMOSOME-3P SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,BLDG 560,ROOM 12-71,FREDERICK,MD 21701. FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21701. NR 1 TC 0 Z9 0 U1 0 U2 10 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 DEC 11 PY 1991 VL 19 IS 23 BP 6660 EP 6660 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GV816 UT WOS:A1991GV81600065 PM 1721708 ER PT J AU YAGUE, J JUAN, M LEONE, A ROMERO, M CARDESA, A VIVES, J STEEG, PS CAMPO, E AF YAGUE, J JUAN, M LEONE, A ROMERO, M CARDESA, A VIVES, J STEEG, PS CAMPO, E TI BGLII AND ECORI POLYMORPHISM OF THE HUMAN NM23-H1 GENE (NME1) SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 HOSP CLIN BARCELONA,SERV ANAT,E-08036 BARCELONA,SPAIN. NCI,PATHOL LAB,BETHESDA,MD 20892. RP YAGUE, J (reprint author), HOSP CLIN BARCELONA,SERV IMMUNOL,VILLARROEL 170,E-08036 BARCELONA,SPAIN. RI Leone, Alvaro/K-6410-2016 OI Leone, Alvaro/0000-0003-3815-9052 NR 2 TC 14 Z9 14 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 DEC 11 PY 1991 VL 19 IS 23 BP 6663 EP 6663 DI 10.1093/nar/19.23.6663 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GV816 UT WOS:A1991GV81600070 PM 1684428 ER PT J AU HECHT, JT WANG, Y RHODES, C YAMADA, Y AF HECHT, JT WANG, Y RHODES, C YAMADA, Y TI TAQI AND HAEIII RFLP POLYMORPHISMS IN HUMAN PROTEOGLYCAN LINK GENE (CRTL1) SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 NIDR,NATL CARIES PROGRAM,BETHESDA,MD 20892. RP HECHT, JT (reprint author), UNIV TEXAS,SCH MED,DEPT PEDIAT,POB 20708,HOUSTON,TX 77225, USA. NR 1 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 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC 11 PY 1991 VL 19 IS 23 BP 6666 EP 6666 DI 10.1093/nar/19.23.6666-a PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GV816 UT WOS:A1991GV81600076 PM 1754418 ER PT J AU HECHT, JT WANG, Y RHODES, C YAMADA, Y AF HECHT, JT WANG, Y RHODES, C YAMADA, Y TI GT REPEAT POLYMORPHISM IN THE HUMAN PROTEOGLYCAN LINK GENE (CRTL1) PROMOTER REGION SO NUCLEIC ACIDS RESEARCH LA English DT Note ID PROTEIN C1 NIDR,NATL CARIES PROGRAM,BETHESDA,MD 20892. RP HECHT, JT (reprint author), UNIV TEXAS,SCH MED,DEPT PEDIAT,POB 20708,HOUSTON,TX 77225, USA. NR 3 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 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC 11 PY 1991 VL 19 IS 23 BP 6666 EP 6666 DI 10.1093/nar/19.23.6666-a PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GV816 UT WOS:A1991GV81600077 PM 1754418 ER PT J AU BUCHHAGEN, DL AF BUCHHAGEN, DL TI MOLECULAR MECHANISMS IN LUNG PATHOGENESIS SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Review ID CANCER CELL-LINES; EPIDERMAL GROWTH-FACTOR; GASTRIN-RELEASING PEPTIDE; SHEEP PULMONARY ADENOMATOSIS; FACTOR RECEPTOR GENE; RETINOBLASTOMA SUSCEPTIBILITY GENE; P53 TUMOR-ANTIGEN; K-RAS ONCOGENE; HUMAN N-MYC; THERAPEUTIC ANTICANCER AGENTS C1 UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. RP BUCHHAGEN, DL (reprint author), NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20814, USA. NR 287 TC 21 Z9 21 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD DEC 10 PY 1991 VL 1072 IS 2-3 BP 159 EP 176 PG 18 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GW263 UT WOS:A1991GW26300004 PM 1751546 ER PT J AU GAWRISCH, K JANZ, S AF GAWRISCH, K JANZ, S TI THE UPTAKE OF PRISTANE (2,6,10,14-TETRAMETHYLPENTADECANE) INTO PHOSPHOLIPID-BILAYERS AS ASSESSED BY NMR, DSC, AND TRITIUM LABELING METHODS SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE PRISTANE; ALKANE; DIOLEOYLPHOSPHATIDYLCHOLINE; LIPOSOME; PLASMACYTOMAGENESIS; NMR; DSC ID MAGNETIC-RESONANCE SPECTROSCOPY; LATERAL DIFFUSION; LIPID BILAYERS; BALB/C MICE; PHOSPHATIDYLCHOLINE; MEMBRANES; ALKANES; HEXANE; MODEL; RAT AB Unilamellar dioleoylphosphatidylcholine (DOPC) liposomes (250-mu-M) incorporated 2 mol% of [H-3]pristane at 37-degrees-C after addition of 50-mu-M pristane solubilized with beta-cyclodextrin. Conventional solubilization in dimethyl sulphoxide resulted in much lower uptake. Premixing of perdeuterated pristane with DOPC and dipalmitoylphosphatidylcholine (DPPC) prior to the formation of multilamellar liposomes resulted in homogeneous incorporation of up to 5 mol% pristane at 22-degrees-C and 50-degrees-C, respectively, as observed by H-2-NMR. Lipid order parameters measured by P-31 and H-2-NMR remained unchanged after pristane uptake. Pristane induced the transformation of part of the dioleoylphosphatidylethanolamine (DOPL)/DOPC (3:1, mol/mol) liquid crystalline lamellar phase into an inverse hexagonal phase. 5 mol% pristane in DPPC bilayers decreased the midpoint of the main phase transition temperature of DPPC from 41.5-degrees-C to 40.9-degrees-C. Upon cooling in the temperature range from 41-degrees-C to 36-degrees-C, pristane was either displaced from the DPPC bilayer or the mode of incorporation changed. These results may aid in defining the mechanisms whereby pristane, an isoprenoid C19-isoalkane, induces plasmacytomagenesis in mice. C1 NCI,GENET LAB,BETHESDA,MD 20892. RP GAWRISCH, K (reprint author), NIH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BLDG 10,ROOM 7N316,BETHESDA,MD 20892, USA. NR 48 TC 10 Z9 10 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD DEC 9 PY 1991 VL 1070 IS 2 BP 409 EP 418 DI 10.1016/0005-2736(91)90081-I PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GW631 UT WOS:A1991GW63100014 PM 1764453 ER PT J AU LIJINSKY, W THOMAS, BJ KOVATCH, RM AF LIJINSKY, W THOMAS, BJ KOVATCH, RM TI DIFFERENCES IN SKIN CARCINOGENESIS BY METHYLNITROSOUREA BETWEEN MICE OF SEVERAL STRAINS SO CANCER LETTERS LA English DT Article DE SKIN TUMORS; PAINTING; MOUSE; STRAINS; NITROSOUREAS ID CD-1 MICE; SENCAR; NITROSOALKYLUREAS; RATS AB To compare the susceptibilities of the skin of different strains of mice to the carcinogenic effect of a directly acting alkylating agent, groups of 20 mice were treated twice a week with 25-mu-l of a solution of methylnitrosourea in methanol. The solution was 0.04M and was applied to the shaved back of female BALB/c, Sencar, CD-1 and Swiss mice for 25 weeks. Four groups of 20 mice of each strain were 8 weeks old at the beginning of treatment. Another four groups were 58 weeks old when treatment began. More of the BALB/c mice developed skin tumors than the other three strains, the Sencar mice somewhat less. Few CD-1 mice developed skin tumors and about one third of the Swiss mice. In all four strains, there were fewer animals with skin tumors among those begun at 58 weeks than in the young mice, but the difference was small. Survival was poor among CD-1 mice, but there was not a large difference between the strains in time of appearance of first tumor, or in average latent period of skin tumors, almost all of which were carcinomas. The Sencar mice were not outstandingly more sensitive to skin carcinogenesis by MNU, as they were to UV radiation-induced skin carcinogenesis. In a comparable study in Swiss mice neither dimethylnitrosourea nor diethylnitrosourea induced skin tumors by painting and both showed only a weak systemic carcinogenic effect in the lungs, although they are directly acting mutagens. C1 NCI,FREDERICK CANC RES & DEV CTR,BASIC RES PROGRAM,ABL,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 13 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD DEC 9 PY 1991 VL 61 IS 1 BP 1 EP 5 DI 10.1016/0304-3835(91)90069-T PG 5 WC Oncology SC Oncology GA GZ750 UT WOS:A1991GZ75000001 PM 1764693 ER PT J AU IWASA, KH LI, MX JIA, M KACHAR, B AF IWASA, KH LI, MX JIA, M KACHAR, B TI STRETCH SENSITIVITY OF THE LATERAL WALL OF THE AUDITORY OUTER HAIR CELL FROM THE GUINEA-PIG SO NEUROSCIENCE LETTERS LA English DT Article DE MECHANOELECTRIC TRANSDUCTION; STRETCH-ACTIVATED CHANNEL; OUTER HAIR CELL; POTASSIUM CURRENT; GUINEA PIG; CYTOSKELETAL STRUCTURE ID OLIVOCOCHLEAR BUNDLE; CURRENTS; COCHLEA AB The inner and outer hair cells of the mammalian hearing organ are mechano-transducer cells. Here we report evidence that the lateral wall of outer hair cells (OHCs) is a mechano-receptor. This mechano-sensitivity appears to complement that of the stereocilia. Patch clamping studies showed that stretching of the membrane patches by suction at the pipette activated potassium channels with 130 pS unit conductance specifically localized in the lateral wall. Application of an osmotic tension to the entire cell membrane under whole-cell recording produced a 10 mV hyperpolarization. The reversal potential and the magnitude of the macroscopic current under voltage clamp were consistent with the single-channel properties of stretch-activated potassium channels. The elongated cylindrical cell body of the OHC is optimally positioned in the cochlea to sense axial force due to the vibrations of the basilar membrane during sound stimulation. This sensitivity can explain the production of a predominantly hyperpolarizing response to sound stimuli, unique to the OHC. Coupled with voltage-dependent OHC motility, the stretch-activated channels may play an important role in producing a mechanical feedback, an indispensable element in cochlear tuning. C1 NIDCD,MOLEC OTOL LAB,BETHESDA,MD 20892. RP IWASA, KH (reprint author), NINCDS,BIOPHYS LAB,BLDG 9,RM 1E124,BETHESDA,MD 20892, USA. OI Iwasa, Kuni/0000-0002-9397-7704 NR 13 TC 42 Z9 44 U1 0 U2 0 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 DEC 9 PY 1991 VL 133 IS 2 BP 171 EP 174 DI 10.1016/0304-3940(91)90562-8 PG 4 WC Neurosciences SC Neurosciences & Neurology GA GX484 UT WOS:A1991GX48400006 PM 1726184 ER PT J AU LO, SC HAYES, MM WANG, RYH PIERCE, PF KOTANI, H SHIH, JWK AF LO, SC HAYES, MM WANG, RYH PIERCE, PF KOTANI, H SHIH, JWK TI NEWLY DISCOVERED MYCOPLASMA ISOLATED FROM PATIENTS INFECTED WITH HIV SO LANCET LA English DT Article ID AIDS; INCOGNITUS; STRAINS; AGENT AB Mycoplasmas have been isolated from patients with acquired immunodeficiency syndrome (AIDS) and they may contribute to the pathogenesis of this disease. We have isolated repeatedly a previously unknown mycoplasma from the urine of an HIV-positive male homosexual and, subsequently, from the urine of 5 HIV-positive patients with AIDS. The mycoplasma was not found in the urine of 98 healthy control subjects. The organism has an unusual tip-like structure with densely packed fine granules and metabolises both glucose and arginine for growth. Antigenic and DNA analyses show the organism to be distinct from other known mycoplasmas. The mycoplasma displays in-vitro activities associated with virulence in vivo. In addition, electronmicroscopy shows that the mycoplasma can invade and attach to various human and animal cells. We are investigating whether the new mycoplasma has a role in human disease. C1 NIH,WARREN GRANT MAGUNSON CLINICAL CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. GEORGETOWN UNIV HOSP,HIV CLIN PROGRAM,WASHINGTON,DC 20007. RP LO, SC (reprint author), ARMED FORCES INST PATHOL,DEPT INFECT & PARASIT DIS PATHOL,AMER REGISTRY PATHOL,WASHINGTON,DC 20306, USA. NR 21 TC 98 Z9 115 U1 0 U2 2 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD DEC 7 PY 1991 VL 338 IS 8780 BP 1415 EP 1418 DI 10.1016/0140-6736(91)92721-D PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA GT904 UT WOS:A1991GT90400003 PM 1683419 ER PT J AU ROONEY, JF BRYSON, Y MANNIX, ML DILLON, M WOHLENBERG, CR BANKS, S WALLINGTON, CJ NOTKINS, AL STRAUS, SE AF ROONEY, JF BRYSON, Y MANNIX, ML DILLON, M WOHLENBERG, CR BANKS, S WALLINGTON, CJ NOTKINS, AL STRAUS, SE TI PREVENTION OF ULTRAVIOLET-LIGHT-INDUCED HERPES LABIALIS BY SUNSCREEN SO LANCET LA English DT Article ID SIMPLEX VIRUS-INFECTION; B IRRADIATION; HUMAN-SKIN; RADIATION; HYPERSENSITIVITY; REACTIVATION; CULTURE; GANGLIA; LATENCY; CELLS AB Sunlight exposure is reported by some patients to precede onset of recurrent herpes labialis. Ultraviolet (UV) B light is known to be a stimulus for the reactivation of herpes simplex virus (HSV) infections. We assessed the effect of a sunblocking agent on UV-light-induced reactivation of recurrent herpes labialis in a double-blind, placebo-controlled crossover trial. 38 patients were exposed on two separate occasions to four minimum erythema doses of UV light at an area of previous labial herpes recurrence. A solution containing sunscreen was applied to the lips before one exposure and a matched placebo before the other. After placebo and UV exposure, herpes labialis developed in 27 (71%) of the 38 patients, with a mean time to recurrence of 2.9 (SEM 0.2) days. In contrast, when sunscreen was applied before UV exposure, no lesions developed, but 1 of the 35 patients shed virus at the exposure site. We conclude that UV light is a potent stimulus for inducing reactivation of herpes labialis, and that application of sunscreen may be effective in the prevention of sunlight-induced recurrent infection. C1 NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,SCH MED,DEPT PEDIAT,LOS ANGELES,CA 90024. RP ROONEY, JF (reprint author), NIDR,ORAL MED LAB,BLDG 30,ROOM 121,BETHESDA,MD 20892, USA. NR 22 TC 95 Z9 97 U1 0 U2 4 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD DEC 7 PY 1991 VL 338 IS 8780 BP 1419 EP 1422 DI 10.1016/0140-6736(91)92723-F PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA GT904 UT WOS:A1991GT90400004 PM 1683420 ER PT J AU KITTUR, DS HOGAN, MM THUKRAL, VK MCGAW, LJ ALEXANDER, JW AF KITTUR, DS HOGAN, MM THUKRAL, VK MCGAW, LJ ALEXANDER, JW TI INCENTIVES FOR ORGAN DONATION SO LANCET LA English DT Editorial Material ID LAW C1 UNITED NETWORK ORGAN SHARING,1100 BOULDERS PKWY,SUITE 500,POB 13770,RICHMOND,VA 23225. TULANE UNIV,MED CTR,SCH PUBL HLTH & TROP MED,NEW ORLEANS,LA 70118. UNIV CINCINNATI,COLL MED,CINCINNATI,OH 45221. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. NIAID,BETHESDA,MD 20892. NR 16 TC 78 Z9 78 U1 1 U2 2 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD DEC 7 PY 1991 VL 338 IS 8780 BP 1441 EP 1443 DI 10.1016/0140-6736(91)92735-K PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA GT904 UT WOS:A1991GT90400015 PM 1683431 ER PT J AU FERRIN, LJ CAMERINIOTERO, RD AF FERRIN, LJ CAMERINIOTERO, RD TI SELECTIVE CLEAVAGE OF HUMAN DNA - RECA-ASSISTED RESTRICTION ENDONUCLEASE (RARE) CLEAVAGE SO SCIENCE LA English DT Article ID TRIPLE-HELIX FORMATION; SITE-SPECIFIC CLEAVAGE; CYSTIC-FIBROSIS GENE; ESCHERICHIA-COLI; PROTEIN; SEQUENCES; IDENTIFICATION; PURIFICATION; CHROMOSOME; DUPLEX AB Current methods for sequence-specific cleavage of large segments of DNA are severely limited because of the paucity of possible cleavage sites. A method is described whereby any Eco RI site can be targeted for specific cleavage. The technique is based on the ability of RecA protein from Escherichia coli to pair an oligonucleotide to its homologous sequence in duplex DNA and to form a three-stranded complex. This complex is protected from Eco RI methylase; after methylation and RecA protein removal, Eco RI restriction enzyme cleavage was limited to the site previously protected from methylation. When pairs of oligonucleotides are used, a specific fragment can be cleaved out of genomes. The method was tested on lambda-phage, Escherichia coli, and human DNA. Fragments exceeding 500 kilobases in length and yields exceeding 80 percent could be obtained. C1 NIDDKD,GENET & BIOCHEM BRANCH,BETHESDA,MD 20892. NR 23 TC 192 Z9 192 U1 2 U2 5 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 6 PY 1991 VL 254 IS 5037 BP 1494 EP 1497 DI 10.1126/science.1962209 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GT903 UT WOS:A1991GT90300036 PM 1962209 ER PT J AU NOONAN, DM FULLE, A VALENTE, P CAI, S HORIGAN, E SASAKI, M YAMADA, Y HASSELL, JR AF NOONAN, DM FULLE, A VALENTE, P CAI, S HORIGAN, E SASAKI, M YAMADA, Y HASSELL, JR TI THE COMPLETE SEQUENCE OF PERLECAN, A BASEMENT-MEMBRANE HEPARAN-SULFATE PROTEOGLYCAN, REVEALS EXTENSIVE SIMILARITY WITH LAMININ-A CHAIN, LOW-DENSITY LIPOPROTEIN-RECEPTOR, AND THE NEURAL CELL-ADHESION MOLECULE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMINO-ACID SEQUENCE; CYSTEINE-RICH REPEATS; HUMAN LDL RECEPTOR; MULTIDOMAIN PROTEIN; CORE PROTEIN; DOMAIN-STRUCTURE; PROMOTING FACTOR; COLLAGEN-IV; BINDING; CDNA AB A heparan sulfate proteoglycan is a component of all basement membranes. This molecule consists of three heparan sulfate side chains linked to a large core protein of approximately 400 kDa. We have isolated seven overlapping murine cDNA clones that encode the entire mRNA sequence of 12.685 kilobases of this molecule. This sequence has a single open reading frame of 3,707 amino acids that encodes for a protein of 396 kDa. Identical or near identical matchups with nine peptide sequences derived from the core protein of the molecule isolated from the Engelbreth-Holm-Swarm tumor were found with the deduced sequence. Sequence analysis and data base comparison of the deduced sequence show the protein to consist of five different domains, most of which contain internal repeats. Domain I contains a start methionine followed by a typical signal transfer sequence and a unique segment of 172 amino acids that contains the three probable sites of heparan sulfate attachment, SGD. Domain II contains four cysteine- and acidic amino acid-rich repeats that are very similar to those found in the LDL receptor and proteins such as GP330. Domain III consists of cysteine-rich and globular regions, both of which show similarity to those in the short arm of the laminin A chain. Domain IV contains 14 repeats of the immunoglobulin superfamily that are most highly similar to the immunoglobulin-like repeats in the neural cell adhesion molecule. Domain V contains three repeats with similarity to the laminin A chain G domain that are separated by epidermal growth factor-like regions not found in the laminin A chain. As the primary structural data agree with the appearance of the molecule in the electron microscope as a series of globules separated by rods, or "beads on a string," we have adopted the name perlecan for this molecule. The variety of domains in perlecan suggest multiple interactions with other molecules. C1 EYE & EAR INST PITTSBURGH,PITTSBURGH,PA. NIDR,BETHESDA,MD 20892. UNIV PITTSBURGH,PITTSBURGH,PA 15260. RP NOONAN, DM (reprint author), IST NAZL RIC CANC,I-16132 GENOA,ITALY. RI Noonan, Douglas/A-8620-2010 OI Noonan, Douglas/0000-0001-8058-0719 FU NEI NIH HHS [EY08098]; NIDCR NIH HHS [F32 DE05417-02]; NIGMS NIH HHS [GM 45389] NR 60 TC 348 Z9 350 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 5 PY 1991 VL 266 IS 34 BP 22939 EP 22947 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GT483 UT WOS:A1991GT48300028 PM 1744087 ER PT J AU TSAI, SC HAUN, RS TSUCHIYA, M MOSS, J VAUGHAN, M AF TSAI, SC HAUN, RS TSUCHIYA, M MOSS, J VAUGHAN, M TI ISOLATION AND CHARACTERIZATION OF THE HUMAN GENE FOR ADP-RIBOSYLATION FACTOR-III, A 20-KDA GUANINE NUCLEOTIDE-BINDING PROTEIN ACTIVATOR OF CHOLERA-TOXIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MESSENGER-RNA; PROMOTER REGION; SEQUENCE; GTP; TRANSCRIPTION; PSEUDOGENE; CLONING; BOVINE; END AB ADP-ribosylation factors (ARFs) are approximately 20-kDa guanine nucleotide-binding proteins that stimulate the ADP-ribosyltransferase activity of cholera toxin in vitro. Five different human ARFs have been identified by cDNA cloning. Northern analysis using ARF 3-specific oligonucleotides identified two mRNAs of 3.7 and 1.2 kilobases (kb). We report here the complete nucleotide sequence of the 3.7-kb ARF 3 mRNA derived from three overlapping cDNAs isolated from human hippocampus and fetal brain cDNA libraries, as well as the structure of human ARF 3 gene. Sequences of two overlapping genomic clones indicated that the ARF 3 gene spans approximately 18.3 kb and contains five exons and four introns. The conserved amino acid sequences involved in guanine nucleotide binding by ARF 3 are distributed among separate exons, as found in other GTP-binding protein genes. Translation initiates in exon 2 which includes the sequence GXXXXGK that probably participates in phosphate binding and GTP hydrolysis. The sequence DVGG in exon 3 coordinates binding of Mg2+ and the beta-phosphate of GDP. In the ARF 3 gene in contrast to those of other GTP-binding proteins, the sequence NKXD (which is thought to contribute to the specificity of interaction with the guanine ring) is divided between exons 4 and 5. The latter encodes the COOH-terminal 53 amino acids of ARF 3 and contains > 2500 base pairs of untranslated DNA. The sequence AATTAA is 19 bases 5' to the polyadenylation addition site of the 3.7-kb mRNA. Multiple transcription start sites were identified by primer extension and S1 and mung bean nuclease analyses. The 5'-flanking region of exon 1 contains neither a TATA nor a CAAT box, but is high in GC content (> 70%) and includes three potential Sp1-binding sites (GC box), consistent with the promoters described for several housekeeping genes. The 1.2-kb ARF 3 mRNA is shown to arise by use of an alternative polyadenylation signal (AACAAA) at nucleotide 1091 within the ARF 3 cDNA. RP TSAI, SC (reprint author), NHLBI,CELLULAR METAB LAB,RM 5N307,BLDG 10,BETHESDA,MD 20892, USA. NR 28 TC 35 Z9 36 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 DEC 5 PY 1991 VL 266 IS 34 BP 23053 EP 23059 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GT483 UT WOS:A1991GT48300045 PM 1744102 ER PT J AU FARSETTI, A MITSUHASHI, T DESVERGNE, B ROBBINS, J NIKODEM, VM AF FARSETTI, A MITSUHASHI, T DESVERGNE, B ROBBINS, J NIKODEM, VM TI MOLECULAR-BASIS OF THYROID-HORMONE REGULATION OF MYELIN BASIC-PROTEIN GENE-EXPRESSION IN RODENT BRAIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EMBRYONIC MOUSE-BRAIN; MYELINOGENESIS INVITRO; DEVELOPMENTAL EXPRESSION; MESSENGER-RNAS; CELLS; IDENTIFICATION; CULTURES; MICE; TRANSCRIPTION; ELEMENTS AB Regulation of myelin basic protein (MBP) gene(~)expression by thyroid hormone has been investigated in rodent brain. Quantitation of the 4 major alternatively spliced transcripts by RNase protection assay showed that the individual mRNAs, corresponding to MBP isoforms 21.5, 18.5, 17, and 14 kDa, were decreased from 2- to 17-fold at all ages studied (4-60 days) in hypothyroid animals when compared to euthyroid, but the timing of onset of expression was not altered. MBP mRNA was also reduced in young adult rats thyroidectomized at the age of 5-6 weeks and was restored to normal by thyroxine administration. Nu-clear run-off assays showed that the rate of MBP gene transcription is dependent on thyroid state. Co-transfection of MBP (-256/+1)-chloramphenicol acetyltransferase chimeric gene with a plasmid expressing thyroid hormone receptor-alpha, and in the presence of 3,5,3'-triiodothyronine, into NIH3T3 or NG108-15, increased chloramphenicol acetyltransferase expression 4-fold. Using a footprinting technique and Spodoptera frugiperda 9 (Sf9) nuclear extract infected with baculovirus expressing TR-alpha, we have identified a single DNA-binding site (-186/-163) for the receptor. A part of this region contains the AGGACA sequence found in thyroid hormone-responsive elements of other 3,5,3'-triiodothyronine-regulated genes. Our finding of a specific hormone-receptor interaction with the MBP promoter region is the first direct demonstration of a thyroid hormone-responsive element in a brain-specific gene. C1 NIDDKD,CLIN ENDOCRINOL BRANCH,BETHESDA,MD 20892. RI Desvergne, Beatrice/C-8892-2016 OI Desvergne, Beatrice/0000-0001-5483-288X NR 39 TC 160 Z9 161 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 5 PY 1991 VL 266 IS 34 BP 23226 EP 23232 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GT483 UT WOS:A1991GT48300069 PM 1720778 ER PT J AU BOWDITCH, RD HALLORAN, CE AOTA, S OBARA, M PLOW, EF YAMADA, KM GINSBERG, MH AF BOWDITCH, RD HALLORAN, CE AOTA, S OBARA, M PLOW, EF YAMADA, KM GINSBERG, MH TI INTEGRIN-ALPHA-IIB-BETA-3 (PLATELET GPIIB-IIIA) RECOGNIZES MULTIPLE SITES IN FIBRONECTIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-BINDING DOMAIN; GLYCOPROTEIN-IIB; PLASMA FIBRONECTIN; PROTEOLYTIC FRAGMENTS; MONOCLONAL-ANTIBODIES; FIBROBLASTIC CELLS; SYNTHETIC PEPTIDES; ADHESION; RECEPTOR; INTEGRINS AB The binding of fibronectin (Fn) to several integrins involves the Arg-Gly-Asp (RGD) tripeptide sequence. However, linear synthetic RGD peptides do not completely mimic the cell attachment activity of intact Fn or certain large Fn fragments. This suggests that the integrin-Fn interaction involves a more extended surface of Fn than that provided by the RGD sequence. To test this possibility, three novel monoclonal anti-Fn antibodies that inhibit its binding to a purified integrin, alpha(IIb)beta-3, were developed. The epitopes of these three antibodies mapped to a region at least 55 residues amino-terminal of the RGD sequence. Further, recombinant fragments of Fn containing these epitopes and lacking the RGD site also inhibited the binding of Fn to purified alpha(IIb)beta-3. These fragments, which spanned Fn residues 1359-1436, bound to alpha(IIb)beta-3 in a divalent cation-dependent manner. In addition, this region of Fn bound specifically to alpha(IIb)beta-3 on thrombin-stimulated but not resting platelets. These results demonstrate the presence of additional sequences in Fn that interact with integrin alpha(IIb)beta-3 and suggest that multiple sites in Fn are involved in its recognition by this integrin. C1 SCRIPPS RES INST, COMM VASC BIOL, LA JOLLA, CA 92037 USA. NIDR, DEV BIOL LAB, BETHESDA, MD 20892 USA. FU NHLBI NIH HHS [HL 28235] NR 51 TC 98 Z9 98 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 5 PY 1991 VL 266 IS 34 BP 23323 EP 23328 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GT483 UT WOS:A1991GT48300082 PM 1720779 ER PT J AU PARK, PW ROBERTS, DD GROSSO, LE PARKS, WC ROSENBLOOM, J ABRAMS, WR MECHAM, RP AF PARK, PW ROBERTS, DD GROSSO, LE PARKS, WC ROSENBLOOM, J ABRAMS, WR MECHAM, RP TI BINDING OF ELASTIN TO STAPHYLOCOCCUS-AUREUS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FIBRONECTIN; LAMININ; STREPTOCOCCI; TROPOELASTIN; RECEPTOR; PROTEIN; MEMBRANE; CELLS AB Many pathogenic bacteria specifically bind to components of the extracellular matrix. In this study, we report the specific association of Staphylococcus aureus with elastin, a major structural component of elastic tissue. Competition assays in which the binding of radiolabeled tropoelastin was inhibited by excess unlabeled elastin peptides, but not by other proteins, established the specificity of the interaction. Kinetic studies showed that tropoelastin binding to the bacteria was rapid and saturable. Scatchard analysis of the equilibrium binding data indicated the presence of a single class of high affinity binding sites (K(D) approximately 4-7 nM) with approximately 1000 sites per organism. Protease susceptibility suggested that the elastin binding moiety on S. aureus was a protein, which was confirmed by the isolation of a 25-kDa elastin-binding protein from S. aureus extracts through affinity chromatography. Using a truncated form of tropoelastin, the bacterial binding domain on elastin was mapped to a 30-kDa fragment at the amino end of the molecule. Although the precise amino acid sequence recognized by the staphylococcal elastin receptor has not been characterized, it is clearly different from the region of tropoelastin that specifies binding to mammalian elastin receptors. C1 WASHINGTON UNIV,JEWISH HOSP ST LOUIS,MED CTR,DEPT PATHOL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT CELL BIOL & PHYSIOL,ST LOUIS,MO 63110. NCI,PATHOL LAB,BETHESDA,MD 20892. UNIV PENN,SCH DENT MED,PHILADELPHIA,PA 19104. WASHINGTON UNIV,JEWISH HOSP ST LOUIS,MED CTR,DEPT MED,ST LOUIS,MO 63110. RI Abrams, William/A-5782-2008; Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU NHLBI NIH HHS [HL41926, HL26499] NR 36 TC 44 Z9 46 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 DEC 5 PY 1991 VL 266 IS 34 BP 23399 EP 23406 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GT483 UT WOS:A1991GT48300093 PM 1744133 ER PT J AU ZIMMERMAN, SB TRACH, SO AF ZIMMERMAN, SB TRACH, SO TI ESTIMATION OF MACROMOLECULE CONCENTRATIONS AND EXCLUDED VOLUME EFFECTS FOR THE CYTOPLASM OF ESCHERICHIA-COLI SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE PROTEINS; CYTOPLASM; EXCLUDED VOLUME; MACROMOLECULAR CROWDING; METABOLIC BUFFERING ID REPRESSOR-OPERATOR INTERACTION; PROTEIN-DNA INTERACTIONS; LAMBDA-PR PROMOTER; LAC REPRESSOR; POLYETHYLENE-GLYCOL; HEMOGLOBIN SOLUTIONS; RNA-POLYMERASE; PRECIPITATION; DEPENDENCE; KINETICS RP NIDDKD, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. NR 85 TC 551 Z9 559 U1 5 U2 74 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD DEC 5 PY 1991 VL 222 IS 3 BP 599 EP 620 DI 10.1016/0022-2836(91)90499-V PG 22 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GV583 UT WOS:A1991GV58300017 PM 1748995 ER PT J AU MCDONALD, NQ LAPATTO, R MURRAYRUST, J GUNNING, J WLODAWER, A BLUNDELL, TL AF MCDONALD, NQ LAPATTO, R MURRAYRUST, J GUNNING, J WLODAWER, A BLUNDELL, TL TI NEW-PROTEIN FOLD REVEALED BY A 2.3-A RESOLUTION CRYSTAL-STRUCTURE OF NERVE GROWTH-FACTOR SO NATURE LA English DT Article ID NEUROTROPHIC FACTOR; MOLECULAR-CLONING; FACTOR RECEPTOR; NEUROTOXIN; BINDING AB NERVE growth factor (NGF) 1 is a member of an expanding family of neurotrophic factors (including brain-derived neurotrophic factor 2 and the neurotrophins 3,4) that control the development and survival of certain neuronal populations both in the peripheral and in the central nervous systems 5. Its biological effects are mediated by a high-affinity ligand-receptor interaction and a tyrosine kinase signalling pathway 6,7. A potential use for NGF and its relatives in the treatment of neurological disorders such as Alzheimer's disease 8 and Parkinson's disease 9 requires an understanding of the structure-function relationships of NGF. NGF is a dimeric molecule, with 118 amino acids per protomer. We report the crystal structure of the murine NGF dimer at 2.3-angstrom resolution, which reveals a novel protomer structure consisting of three antiparallel pairs of beta-strands, together forming a flat surface. Two subunits associate through this surface, thus burying a total of 2,332 angstrom 2. Four loop regions, which contain many of the variable residues observed between different NGF-related molecules, may determine the different receptor specificities. A clustering of positively charged side chains may provide a complementary interaction with the acidic low-affinity NGF receptor. The structure provides a model for rational design of analogues of NGF and its relatives and for testing the NGF-receptor recognition determinants critical for signal transduction. C1 UNIV LONDON BIRKBECK COLL,IMPERIAL CANC RES FUND,STRUCT MOLEC BIOL UNIT,MALET ST,LONDON WC1E 7HX,ENGLAND. UNIV LONDON BIRKBECK COLL,DEPT CRYSTALLOG,LONDON WC1E 7HX,ENGLAND. NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,FREDERICK,MD 21701. NR 39 TC 395 Z9 400 U1 2 U2 12 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD DEC 5 PY 1991 VL 354 IS 6352 BP 411 EP 414 DI 10.1038/354411a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GT761 UT WOS:A1991GT76100057 PM 1956407 ER PT J AU HEALY, B AF HEALY, B TI ASPIRIN AND WARFARIN EFFECTIVE IN PREVENTING STROKE AND EMBOLISM IN PATIENTS WITH ATRIAL-FIBRILLATION SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP HEALY, B (reprint author), NIH,BLDG 31,ROOM 2B23,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 4 PY 1991 VL 266 IS 21 BP 2955 EP 2955 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GR775 UT WOS:A1991GR77500006 PM 1668176 ER PT J AU HEALY, B AF HEALY, B TI ORAL-ADMINISTRATION OF ACYCLOVIR APPEARS INEFFECTIVE IN TREATING ACUTE INFECTIOUS-MONONUCLEOSIS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP HEALY, B (reprint author), NIH,BLDG 31,ROOM 2B23,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 4 PY 1991 VL 266 IS 21 BP 2955 EP 2955 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GR775 UT WOS:A1991GR77500008 PM 1668176 ER PT J AU HEALY, B AF HEALY, B TI CURRENTLY LICENSED IMMUNOASSAYS DO NOT ACCURATELY DISTINGUISH ANTIBODIES TO HERPES-SIMPLEX VIRUS SUBTYPES SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP HEALY, B (reprint author), NIH,BLDG 31,ROOM 2B23,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 4 PY 1991 VL 266 IS 21 BP 2955 EP 2955 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GR775 UT WOS:A1991GR77500007 PM 1668176 ER PT J AU DESMET, MD NUSSENBATT, RB AF DESMET, MD NUSSENBATT, RB TI OCULAR MANIFESTATIONS OF AIDS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID IMMUNE-DEFICIENCY SYNDROME; CYTOMEGALO-VIRUS RETINITIS; ACQUIRED IMMUNODEFICIENCY SYNDROME; GANCICLOVIR; RETINOPATHY; FOSCARNET; DISEASE RP DESMET, MD (reprint author), NEI,IMMUNOL LAB,BLDG 10,ROOM 10N202,BETHESDA,MD 20892, USA. OI de Smet, Marc/0000-0002-9217-5603 NR 24 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 4 PY 1991 VL 266 IS 21 BP 3019 EP 3022 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA GR775 UT WOS:A1991GR77500036 PM 1668177 ER PT J AU RITTER, JK OWENS, IS NEGISHI, M NAGATA, K SHEEN, YY GILLETTE, JR SASAME, HA AF RITTER, JK OWENS, IS NEGISHI, M NAGATA, K SHEEN, YY GILLETTE, JR SASAME, HA TI MOUSE PULMONARY CYTOCHROME-P-450 NAPHTHALENE HYDROXYLASE - CDNA CLONING, SEQUENCE, AND EXPRESSION IN SACCHAROMYCES-CEREVISIAE SO BIOCHEMISTRY LA English DT Article ID LIVER; RAT; MICE; STEREOSELECTIVITY; IDENTIFICATION; SUPERFAMILY; ENZYME; DAMAGE; CELLS; ACID AB We have isolated a cDNA clone, Nah-2, encoding the cytochrome P-450Nah (naphthalene hydroxylase) from a mouse lung lambda-ZAP cDNA library using anti-cytochrome P-450Nah IgG as a probe. This same antibody selectively blocked [Nagata, K., Martin, B. M., Gillette, J. R., & Sasame, H. A. (1990) Drug Metab. Dispos. 18, 557-564] the cytochrome P-450 in mouse lung microsomes that catalyzed the conversion of naphthalene to (IR,2S)-naphthalene 1,2-oxide, which has been postulated as a causative agent in the naphthalene-induced tissue-specific necrosis of Clara cells in mouse lung. The toxic effect is seen in mouse and not in rat. The cDNA encodes a polypeptide of 491 amino acids with a molecular mass of 50 kDa. Northern blot analysis with an Nah-2-specific probe revealed that the mRNA is expressed in a species-and tissue-specific manner, present only in mouse lung and liver and not in that of rat. The mRNA encoding Nah-2 is constitutively expressed and is not induced by either phenobarbital, pyrazole, pregnenolone 16-alpha-carbonitrile, or 3-methylcholanthrene. Comparative amino acid sequence analyses with other documented members of the P-450 gene superfamily revealed that this encoded protein is in the IIF subfamily. To analyze its substrate specificity, the cDNA was inserted into the vector, pAAH5, and expressed in the Saccharomyces cerevisiae strain, AH22. The presence of cytochrome P-450Nah in the microsomes isolated from transformed cells and analyzed by Western blot was confirmed by immunocomplexing product with anti-cytochrome P450Nah IgG. Furthermore, activity toward naphthalene in the microsomes from the transformed cells established that this clone encodes a naphthalene hydroxylase. Like lung microsomes and purified and reconstituted cytochrome P450Nah, transformed yeast microsomes convert naphthalene primarily to the trans-(1R)-hydroxy-(2R)-glutathionyl-1,2-dihydronaphthalene conjugate, a stable form of the putative toxicant (IR,2S) oxide in the presence of glutathione and a mixture of glutathione S-transferases. Results of immunochemical studies support a role of this cytochrome P-450 in lung toxicity in mice exposed to high doses of naphthalene. C1 NICHHD,NATL HEART LUNG & BLOOD INST,GENET DISORDERS DRUG METAB SECT,BETHESDA,MD 20892. NIEHS,PHARMACOL LAB,RES TRIANGLE PK,NC 27709. NR 40 TC 50 Z9 53 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 3 PY 1991 VL 30 IS 48 BP 11430 EP 11437 DI 10.1021/bi00112a009 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GT485 UT WOS:A1991GT48500009 PM 1742282 ER PT J AU AMBROZ, C CLARK, AJL CATT, KJ AF AMBROZ, C CLARK, AJL CATT, KJ TI THE MAS ONCOGENE ENHANCES ANGIOTENSIN-INDUCED [CA-2+]I RESPONSES IN CELLS WITH PREEXISTING ANGIOTENSIN-II RECEPTORS SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Note DE MAS-ONCOGENE; ANGIOTENSIN-II RECEPTOR; (XENOPUS OOCYTE); (COS-1 CELL LINE) ID CALCIUM MOBILIZATION; RAT-BRAIN; EXPRESSION; OOCYTES; ASSAY; LINE; RNA AB The proposal that the mas oncogene is an angiotensin receptor was evaluated in Xenopus oocytes injected with human and rat mas RNA transcripts, and during transient expression of mas in several cell lines. No evidence of mas-induced angiotensin II (AII) receptors or [Ca2+]i responses was observed in Xenopus oocytes or in most of the transfected cells. However, Cos-1 cells, which showed a small endogenous [Ca2+]i response to AII, exhibited a modest but reproducible enhancement of this response after mas transfection. Such responses were inhibited by [Sar1, Ala8]AII and [Sar1, Ile8]AII, but not by [D-Arg1, D-Pro2, D-Trp7,9, Leu11]substance P, an antagonist reported to inhibit mas-induced responses to AII in oocytes. These findings are not compatible with the proposal that the mas oncogene is an angiotensin receptor, but suggest that expression of mas leads to increased responsiveness of the endogenous AII signaling system. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,ROOM B1-L400,BLDG 10,BETHESDA,MD 20892. FU NICHD NIH HHS [HDO7383-03] NR 21 TC 45 Z9 45 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD DEC 3 PY 1991 VL 1133 IS 1 BP 107 EP 111 DI 10.1016/0167-4889(91)90248-V PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GW104 UT WOS:A1991GW10400015 PM 1721543 ER PT J AU NAKABAYASHI, H SELLERS, JR HUANG, KP AF NAKABAYASHI, H SELLERS, JR HUANG, KP TI CATALYTIC FRAGMENT OF PROTEIN-KINASE-C EXHIBITS ALTERED SUBSTRATE-SPECIFICITY TOWARD SMOOTH-MUSCLE MYOSIN LIGHT CHAIN SO FEBS LETTERS LA English DT Article DE PROTEIN KINASE-C; MYOSIN LIGHT CHAIN; PHOSPHORYLATION ID HEAVY-MEROMYOSIN; PHOSPHORYLATION; ACTIVATION; SITES; PURIFICATION; PLATELETS; FORMS AB Smooth muscle myosin light chain (LC) can be phosphorylated by myosin light chain kinase (MLCK) at Ser19 and Thr18 and by protein kinase C (PKC) at Thr9 and Ser1 or Ser2 under the in vitro assay conditions. Conversion of PKC to the spontaneously active protein kinase M (PKM) by proteolysis resulted in a change in the substrate specificity of the kinase. PKM phosphorylated both sets of sites in LC recognized by MLCK and PKC as analyzed by peptide mapping analysis. The PKM-catalyzed phosphorylation of these sites was not greatly affected by a MLCK inhibitor, ML-9, nor by the activators of MLCK, Ca2+ and calmodulin. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,BLDG 10,ROOM B1L-400,BETHESDA,MD 20892. NHLBI,MOLEC CARDIOL LAB,BETHESDA,MD 20892. NR 25 TC 37 Z9 37 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD DEC 2 PY 1991 VL 294 IS 1-2 BP 144 EP 148 DI 10.1016/0014-5793(91)81362-C PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA GV806 UT WOS:A1991GV80600034 PM 1743284 ER PT J AU AUBORN, KJ WOODWORTH, C DIPAOLO, JA BRADLOW, HL AF AUBORN, KJ WOODWORTH, C DIPAOLO, JA BRADLOW, HL TI THE INTERACTION BETWEEN HPV INFECTION AND ESTROGEN METABOLISM IN CERVICAL CARCINOGENESIS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID HUMAN PAPILLOMAVIRUS TYPE-16; HUMAN-BREAST-CANCER; RETINOBLASTOMA GENE-PRODUCT; EPITHELIAL-CELLS; ESTRADIOL; TRANSFORMATION; PROGESTERONE; WOMEN; TRANSCRIPTION; RECEPTOR AB Cancer of the genital tract is the final outcome of some infections with human papillomavirus (HPVs), and the most estrogen-sensitive cells are at greatest risk for the HPV-related cancers. Therefore we investigated relationships between HPVs and estrogen metabolism in cells of the genital tract. Increased conversion of estradiol to 16-alpha-hydroxyestrone, known to be a risk factor for cancer in some other estrogen-sensitive cells, was investigated in keratinocytes from the genital tract. Primary cells, particularly those explants from the transformation zone of the cervix, are able to 16-alpha-hydroxylate estradiol. Both cervical and foreskin cells immortalized with HPV-16 are greatly enhanced in the 16-alpha-a-hydroxylation of estradiol as compared with normal cells. We suggest a model whereby the combined action of 16-alpha-hydroxylation of estrogen and HPV work together to promote cell proliferation. C1 NCI,BETHESDA,MD 20892. INST HORMONE RES,NEW YORK,NY 10016. RP AUBORN, KJ (reprint author), LONG ISL JEWISH MED CTR,DEPT OTOLARYNGOL,NEW HYDE PK,NY 11042, USA. OI Bradlow, H Leon/0000-0002-2397-3679 NR 33 TC 75 Z9 80 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 2 PY 1991 VL 49 IS 6 BP 867 EP 869 DI 10.1002/ijc.2910490611 PG 3 WC Oncology SC Oncology GA GT956 UT WOS:A1991GT95600010 PM 1660039 ER PT J AU LAMPARSKI, DM ROY, A NUTT, DJ LINNOILA, M AF LAMPARSKI, DM ROY, A NUTT, DJ LINNOILA, M TI THE CRITERIA OF CLONINGER ET-AL AND VONKNORRING ET-AL FOR SUBGROUPING ALCOHOLICS - A COMPARISON IN A CLINICAL POPULATION SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE ALCOHOLISM; SUBTYPE ID PLATELET MAO ACTIVITY; DIAGNOSTIC-CRITERIA; PERSONALITY-TRAITS; ONSET; AGE AB There is increasing evidence that meaningful subgroups of alcoholics may exist. Cloninger et al. and von Knorring et al. have developed criteria to delineate what both call type 1 and type 2 alcoholism. However, when we compared their criteria in a predominantly inpatient sample of male alcoholics, we found large differences between the approaches in identifying type 1 and type 2 alcoholism. Concordance was equally low in a subsample of 34 alcoholics exhibiting antisocial behavior and when subjects were divided by whether the first alcohol-related problem began before or after 20 years of age. Similar findings emerged when we limited our analyses to primary alcoholics and alcoholics with no other mental disorders. C1 NIAAA,DIV INTRAMURAL BIOL & CLIN RES,CLIN STUDIES LAB,BLDG 10,RM 3B19,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 17 TC 34 Z9 34 U1 2 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD DEC PY 1991 VL 84 IS 6 BP 497 EP 502 DI 10.1111/j.1600-0447.1991.tb03183.x PG 6 WC Psychiatry SC Psychiatry GA GY236 UT WOS:A1991GY23600002 PM 1792921 ER PT J AU ROY, A ADINOFF, B DEJONG, J LINNOILA, M AF ROY, A ADINOFF, B DEJONG, J LINNOILA, M TI CEREBROSPINAL-FLUID VARIABLES AMONG ALCOHOLICS LACK SEASONAL-VARIATION SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE SEASON; CEREBROSPINAL FLUID; SEROTONIN; ALCOHOLISM ID CORTICOTROPIN-RELEASING HORMONE; DIAZEPAM-BINDING INHIBITOR; DEPRESSED-PATIENTS; MONOAMINE METABOLITES; ALZHEIMERS-DISEASE; CSF; SOMATOSTATIN; GALANIN; ACID AB Seasonal influences on indices of serotonergic function, including cerebrospinal fluid (CSF) concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), have been reported in psychiatric patients and healthy volunteers. We examined seasonal differences in CSF concentrations of 5-HIAA among 135 alcoholics admitted to a research ward who had a lumbar puncture. No significant seasonal differences were found for either CSF concentrations of 5-HIAA or CSF concentrations of other monoamine metabolites or peptides. The possible explanations for these negative findings are discussed. C1 NIAAA,DIV INTRAMURAL BIOL & CLIN RES,CLIN STUDIES LAB,BETHESDA,MD. MED UNIV S CAROLINA,DEPT PSYCHIAT & BEHAV SCI,CHARLESTON,SC 29425. VET ADM MED CTR,CHARLESTON,SC 29403. NR 28 TC 8 Z9 8 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD DEC PY 1991 VL 84 IS 6 BP 579 EP 582 DI 10.1111/j.1600-0447.1991.tb03199.x PG 4 WC Psychiatry SC Psychiatry GA GY236 UT WOS:A1991GY23600018 PM 1724338 ER PT J AU WITTEK, AE MITCHELL, CD ARMSTRONG, GR ALBINI, A MARTIN, GR SEEMANN, R LEVENBOOK, IS WIERENGA, DE RIDGE, J DUNLAP, RC LUNDQUIST, ML STEIS, RG LONGO, DL MULLER, J QUINNAN, GV AF WITTEK, AE MITCHELL, CD ARMSTRONG, GR ALBINI, A MARTIN, GR SEEMANN, R LEVENBOOK, IS WIERENGA, DE RIDGE, J DUNLAP, RC LUNDQUIST, ML STEIS, RG LONGO, DL MULLER, J QUINNAN, GV TI PROPAGATION AND PROPERTIES OF KAPOSIS SARCOMA-DERIVED CELL-LINES OBTAINED FROM PATIENTS WITH AIDS - SIMILARITY OF CULTURED-CELLS TO SMOOTH-MUSCLE CELLS SO AIDS LA English DT Article DE KAPOSIS SARCOMA; AIDS; SMOOTH MUSCLE CELLS; CULTIVATION INVITRO ID HUMAN-ENDOTHELIAL CELLS; VIII-RELATED ANTIGEN; LONG-TERM CULTURE; MONOCLONAL-ANTIBODIES; BASEMENT-MEMBRANE; INVASIVE ACTIVITY; HOMOSEXUAL MEN; GROWTH-FACTOR; IDENTIFICATION; MARKERS AB Cells derived from Kaposi's sarcoma (KS) were propagated in vitro using conditions which resulted in elimination of contaminating fibroblasts and the emergence of homogeneous cell populations which morphologically resembled smooth muscle cells and had neoplastic characteristics. In long-term culture, they differentiated into large ribbon-like cells with longitudinal fibrillarity of their cytoplasm. These fibrils stained red by Masson trichrome staining, and were reactive with antibodies to desmin. Dense bodies typical of myoblasts were observed in some cells by electron microscopy. The cells did not form capillary structures like endothelial cells, they lacked Weible-Palade bodies, and did not express the blood-clotting Factor VIII-related antigen or receptors for the lectin Ulex europaeus agglutinin I. They did express four other antigens, however, in common with endothelial cells. The cells did not form tumors in athymic nude mice; however, they formed colonies in soft agar, manifested tumor-like growth on muscle organ cultures, and were invasive in an artificial basement membrane invasion assay. The results indicate that a component of KS is closely related to leiomyoblasts and and has neoplastic properties. C1 NIDR,DEV BIOL & ANOMALIES LAB,BETHESDA,MD 20892. US FDA,DIV VIROL,BETHESDA,MD 20014. US FDA,CTR BIOL EVALUAT & RES,PROD QUAL CONTROL,BETHESDA,MD 20014. NCI,FREDERICK CANC RES FACIL,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701. NR 44 TC 30 Z9 30 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 DEC PY 1991 VL 5 IS 12 BP 1485 EP 1493 DI 10.1097/00002030-199112000-00011 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA GW762 UT WOS:A1991GW76200011 PM 1814330 ER PT J AU ARYA, SK AF ARYA, SK TI HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-2 (HIV-2) GENE-EXPRESSION - DOWN-MODULATION BY SEQUENCE ELEMENTS DOWNSTREAM OF THE TRANSCRIPTIONAL INITIATION SITE SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID LONG TERMINAL REPEAT; NECROSIS FACTOR-ALPHA; ACTIVATION-RESPONSIVE REGION; HUMAN RETROVIRUS; HTLV-III; MUTATIONAL ANALYSIS; CELLULAR PROTEINS; BINDING-PROTEINS; TRANS-ACTIVATOR; NUCLEAR-PROTEIN AB Human immunodeficiency virus type 2 (HIV-2) gene expression is downmodulated by sequence elements downstream of the transcriptional initiation site, corresponding to the U5 region of the long terminal repeat (LTR) and further downstream. This repression appeared to be related more to the length of the sequence intervening the transcriptional initiation site and the coding region than to a particular sequence content. The repressive effect of the downstream segment was not affected by HIV-2 and HIV-1 TAT or by the cytomegalovirus transactivator IE-2 gene. Nor was it affected by T-cell activation signals or by such cytokines as tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interferon-gamma (IFN-gamma), and interferon-alpha (IFN-alpha). In contrast to HIV-1, HIV-2 LTR-directed gene expression was not modulated by TNF-alpha. A specific sequence element, located downstream of the TAR element in the R region, seemed to participate in modulation of gene expression. This element interacted with a nuclear protein with a mobility of about 26 kD. The repressive effect of the downstream sequence was to a certain extent cell type dependent, suggesting the involvement of cell type-specific factors. It was more effective in human lymphocytic CEM cells than in Jurkat cells. This may be relevant to the HIV-2 cell tropism (replication), latency, and virulence. RP ARYA, SK (reprint author), NCI,TUMOR CELL BIOL LAB,BLDG 37,ROOM 6A09,BETHESDA,MD 20892, USA. NR 56 TC 8 Z9 8 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 DEC PY 1991 VL 7 IS 12 BP 1007 EP 1014 DI 10.1089/aid.1991.7.1007 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA GW624 UT WOS:A1991GW62400007 PM 1812941 ER PT J AU OLSON, MC RAMAKRISHNAN, S ANAND, R AF OLSON, MC RAMAKRISHNAN, S ANAND, R TI RIBOSOMAL INHIBITORY PROTEINS FROM PLANTS INHIBIT HIV-1 REPLICATION IN ACUTELY INFECTED PERIPHERAL-BLOOD MONONUCLEAR-CELLS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID RICIN-A-CHAIN; SYNDROME AIDS; T-CELLS; TRICHOSANTHIN; RETROVIRUS; INVITRO; ALPHA AB Peripheral blood mononuclear cells from seronegative donors were stimulated with phytohemagglutinin and then infected with human immunodeficiency virus (HIV-1). Using this experimental system, the antiviral activity of two translation inhibitory proteins (pokeweed antiviral protein, PAP-S, and Luffa ribosomal inhibitory protein, LRIP-I) isolated from plants and a recombinant form of ricin A chain were studied. Previously, it had been shown that toxin polypeptides linked to monoclonal antibodies could inhibit HIV-infected cells. In the present study, the free, unconjugated, proteins were found to inhibit HIV replication at doses in which they were nontoxic to uninfected peripheral blood mononuclear cells. Among the inhibitory proteins, PAP-S and recombinant ricin A chain markedly reduced the reverse transcriptase activity and the expression of p24 core protein in infected cultures. Dose response studies indicate that the anti-HIV activity of PAP-S was comparable to AZT. The other ribosome inhibitory proteins (RIPs) showed moderate but significant antiviral activity. C1 NIAID,AIDS REVIEW SECT,DEA,BETHESDA,MD 20892. NIAID,CBER,FDA,RETROVIROL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA-48068] NR 27 TC 27 Z9 33 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 DEC PY 1991 VL 7 IS 12 BP 1025 EP 1030 DI 10.1089/aid.1991.7.1025 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA GW624 UT WOS:A1991GW62400010 PM 1725958 ER PT J AU HANNA, EZ AF HANNA, EZ TI ATTITUDES TOWARD PROBLEM DRINKERS, REVISITED - PATIENT-THERAPIST FACTORS CONTRIBUTING TO THE DIFFERENTIAL TREATMENT OF PATIENTS WITH ALCOHOL-PROBLEMS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE PROBLEM DRINKER; STEREOTYPE; ATTITUDES; TREATMENT ID RESIDENTS; DIAGNOSIS AB Although there are many treatment alternatives open to people with drinking problems, health professionals still exhibit negative attitudes towards alcoholics. In a previous study, the author demonstrated that those patients who were self-labelled alcoholics were treated in a less preferential manner than those who did not identify as such. This study used both overt and unobtrusive measures to determine whether negative attitudes of intake interviewers towards problem drinkers were elicited by the patient's self-label as an alcoholic or by other variables related to perceived treatment outcome. Pre- and postinterview data on patient likability, doctor's eagerness to work with the patient, interview content, treatment disposition, and patient compliance were collected from first-time patients, and from their interviewers, in the walk-in psychiatry and alcohol treatment units of a large, urban teaching hospital. The results elucidate how stereotypes interact with patient characteristics to influence both professional behavior and patient compliance. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. RP HANNA, EZ (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,5600 FISHERS LANE,ROOM 14C-26,ROCKVILLE,MD 20857, USA. NR 17 TC 11 Z9 11 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 1991 VL 15 IS 6 BP 927 EP 931 DI 10.1111/j.1530-0277.1991.tb05190.x PG 5 WC Substance Abuse SC Substance Abuse GA GV648 UT WOS:A1991GV64800005 PM 1665015 ER PT J AU CLYNE, CA ARRIGHI, JA MARON, BJ DILSIZIAN, V BONOW, RO CANNON, RO AF CLYNE, CA ARRIGHI, JA MARON, BJ DILSIZIAN, V BONOW, RO CANNON, RO TI SYSTEMIC AND LEFT-VENTRICULAR RESPONSES TO EXERCISE STRESS IN ASYMPTOMATIC PATIENTS WITH VALVULAR AORTIC-STENOSIS SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID HYPERTROPHIC CARDIOMYOPATHY; VALVE-REPLACEMENT; SYSTOLIC FUNCTION; CHILDREN; ELECTROCARDIOGRAM; DETERMINANTS; HEMODYNAMICS; PRESSURE; REST AB Patients with heart disease may have myocardial ischemia or left ventricular (LV) dysfunction without symptoms. The exercise responses of 14 asymptomatic patients with valvular aortic stenosis (AS) were studied using treadmill testing, thallium-201 scintigraphy and radionuclide angiography. Compared with age- and gender-matched control subjects, patients with AS demonstrated reduced exercise tolerance (10.7 +/- 2.5 vs 13.3 +/- 4.2 min; p = 0.06) and maximal oxygen consumption (26.7 +/- 6.3 vs 36.3 +/- 9.5 ml O2/min/kg; p = 0.004) associated with decreased peak systolic blood pressure response to exercise (177 +/- 18 vs 214 +/- 42 mm Hg; p < 0.004). Ten of 14 patients developed ST-segment depression during exercise, only 3 of whom had reversible thallium defects. Patients with AS tended to have greater LV ejection fractions at rest (65 +/- 11 vs 58 +/- 7; p = 0.08) and significantly decreased early peak filling rates (4.8 +/- 1.3 vs 6.1 +/- 0.6 stroke volume/s; p = 0.003) compared with those of control subjects. During maximal supine exercise, patients with AS had less of an increase in ejection fraction (2 +/- 9 vs 15 +/- 7%; p < 0.001) associated with a decrease in end-diastolic (-7 +/- 15 vs +5 +/- 16%; p = 0.06) and stroke (-6 +/- 17 vs +30 +/- 13%; p < 0.001) volumes from baseline measurements. The limitation in stroke volume and heart rate to exercise stress in patients with AS was associated with attenuation of the cardiac output response during exercise compared with that of control subjects (73 +/- 48 vs 284 +/- 48%; p < 0.001), which correlated directly with effort limitation (r = 0.717, p = 0.004). Thus, despite the absence of symptoms patients with AS demonstrated limited effort tolerance with abnormal systemic and LV hemodynamics, which is most likely a consequence of the inability to augment end-diastolic volume during exercise. C1 NHLBI,CARDIOL BRANCH,CARDIOVASC DIAG SECT,BLDG 10,RM 7B15,BETHESDA,MD 20892. NHLBI,CARDIOL BRANCH,NUCL CARDIOL SECT,BETHESDA,MD 20892. NR 32 TC 55 Z9 56 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 1 PY 1991 VL 68 IS 15 BP 1469 EP 1476 DI 10.1016/0002-9149(91)90281-O PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA GT331 UT WOS:A1991GT33100011 PM 1746429 ER PT J AU BUTLER, JD BERGSTEN, P WELCH, RW LEVINE, M AF BUTLER, JD BERGSTEN, P WELCH, RW LEVINE, M TI ASCORBIC-ACID ACCUMULATION IN HUMAN SKIN FIBROBLASTS SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT CONF ON ASCORBIC ACID : BIOLOGIC FUNCTIONS AND RELATION TO CANCER CY SEP 10-12, 1990 CL NIH, BETHESDA, MD SP NCI, NIDDKD HO NIH DE ASCORBIC ACID; FIBROBLASTS; TRANSPORT; COLLAGEN AB The transport and accumulation of ascorbic acid in normal human skin fibroblasts in culture was investigated by using high-performance liquid chromatographic separation and coulometric electrochemical detection. Results measured as picomole ascorbic acid per microgram cell protein were expressed in molar amounts after determining the volume of skin fibroblasts. Confluent fibroblasts contained undetectable amounts of ascorbic acid. On incubation with micromole per liter amounts of ascorbic acid in the medium, cells showed increasing uptake of ascorbic acid with time, accumulating a 15-fold excess in 3.5 h. Kinetic experiments suggested two transport mechanisms, a high-affinity and a low-affinity transport activity. Both transport activities were temperature sensitive and accumulated ascorbic acid against a concentration gradient. C1 NIDDKD,CELL BIOL & GENET LAB,BLDG 8,ROOM 415,BETHESDA,MD 20892. NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. RP LEVINE, M (reprint author), NIDDKD,CELL BIOL & GENET LAB,BLDG 8,ROOM 415,BETHESDA,MD 20892, USA. NR 5 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC CLIN NUTRITION INC PI BETHESDA PA 9650 ROCKVILLE PIKE SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 1991 VL 54 IS 6 SU S BP S1144 EP S1146 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA GU397 UT WOS:A1991GU39700008 ER PT J AU GARLAND, DL AF GARLAND, DL TI ASCORBIC-ACID AND THE EYE SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT CONF ON ASCORBIC ACID : BIOLOGIC FUNCTIONS AND RELATION TO CANCER CY SEP 10-12, 1990 CL NIH, BETHESDA, MD SP NCI, NIDDKD HO NIH DE ASCORBIC ACID; EYE; LENS PROTEINS ID RETINAL LIGHT DAMAGE; IRIS-CILIARY BODY; VITAMIN-C; AQUEOUS-HUMOR; SENILE CATARACT; GUINEA-PIG; TRABECULAR MESHWORK; ACTIVE-TRANSPORT; NUCLEAR CATARACT; LENS CRYSTALLINS AB In this report literature on transport and function of ascorbic acid in ocular tissues is reviewed. The role of ascorbic acid in various regions of the eye is not well understood. It appears one important function of this compound is protection against oxidative damage, particularly photoinduced damage. In contrast, data are also reviewed that suggest ascorbic acid may participate in the oxidative modification of lens proteins seen with aging. RP GARLAND, DL (reprint author), NEI,MECHANISMS OCULAR DIS LAB,BLDG 6,ROOM 235,BETHESDA,MD 20892, USA. NR 78 TC 46 Z9 48 U1 0 U2 3 PU AMER SOC CLIN NUTRITION INC PI BETHESDA PA 9650 ROCKVILLE PIKE SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 1991 VL 54 IS 6 SU S BP S1198 EP S1202 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA GU397 UT WOS:A1991GU39700018 ER PT J AU LEVINE, M DHARIWAL, KR WASHKO, PW BUTLER, JD WELCH, RW WANG, YH BERGSTEN, P AF LEVINE, M DHARIWAL, KR WASHKO, PW BUTLER, JD WELCH, RW WANG, YH BERGSTEN, P TI ASCORBIC-ACID AND INSITU KINETICS - A NEW APPROACH TO VITAMIN REQUIREMENTS SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT CONF ON ASCORBIC ACID : BIOLOGIC FUNCTIONS AND RELATION TO CANCER CY SEP 10-12, 1990 CL NIH, BETHESDA, MD SP NCI, NIDDKD HO NIH DE INSITU KINETICS; ASCORBIC ACID; NOREPINEPHRINE SYNTHESIS ID COULOMETRIC ELECTROCHEMICAL DETECTION; PERFORMANCE LIQUID-CHROMATOGRAPHY; BETA-MONOOXYGENASE ACTIVITY; CHROMAFFIN GRANULES; NOREPINEPHRINE BIOSYNTHESIS; DEHYDROASCORBIC ACID; ADRENAL-MEDULLA; CELLS; HYDROXYLASE; SCURVY AB Ascorbic acid requirements are based on preventing the deficiency disease scurvy and on urinary excretion of vitamin C. We proposed the first quantitative approach to determining optimal requirements for ascorbic acid and other vitamins, called in situ kinetics. In situ kinetics biochemically is based on the application of Michaelis-Menten reaction kinetics to ascorbic acid-dependent reactions in situ. Clinically in situ kinetics is based on determining vitamin availability to tissues, so that cell-specific reactions can occur. The biochemical concepts of in situ kinetics are verified for the first time through studying ascorbic acid regulation of norepinephrine biosynthesis. The principles of in situ kinetics can now be applied to humans and human cells and for determining optimal requirements for ascorbic acid and for other vitamins. C1 NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. RP LEVINE, M (reprint author), NIDDKD,CELL BIOL & GENET LAB,BLDG 8,ROOM 415,BETHESDA,MD 20892, USA. NR 42 TC 24 Z9 24 U1 2 U2 2 PU AMER SOC CLIN NUTRITION INC PI BETHESDA PA 9650 ROCKVILLE PIKE SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 1991 VL 54 IS 6 SU S BP S1157 EP S1162 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA GU397 UT WOS:A1991GU39700011 ER PT J AU MARGOLIS, SA ZIEGLER, RG HELZLSOUER, KJ AF MARGOLIS, SA ZIEGLER, RG HELZLSOUER, KJ TI ASCORBIC AND DEHYDROASCORBIC ACID MEASUREMENT IN HUMAN SERUM AND PLASMA SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT CONF ON ASCORBIC ACID : BIOLOGIC FUNCTIONS AND RELATION TO CANCER CY SEP 10-12, 1990 CL NIH, BETHESDA, MD SP NCI, NIDDKD HO NIH DE ASCORBIC; DEHYDROASCORBIC; HUMAN SERUM; STABILITY; REFERENCE MATERIALS; CANCER-FREE FEMALES; JUVENILE RHEUMATOID ARTHRITIS; LABORATORY PERFORMANCE; WHOLE BLOOD ID PERFORMANCE LIQUID-CHROMATOGRAPHY; VITAMIN-C; ELECTROCHEMICAL DETECTION; SMOKERS AB Plasma supplemented with ascorbic acid was prepared; the stability of these samples was characterized and the accuracy of the supplementation was established. Studies on the accuracy, precision, and sources of methodological bias in the measurement of ascorbic acid were summarized. Measurements of the ratio of ascorbic acid to dehydroascorbic acid in clinical samples was evaluated and was shown to be relatively constant in plasma taken from blood stored at 12-degrees-C for 6 h. These results imply that whole blood has the capacity to maintain a constant ascorbic-dehydroascorbic acid ratio and suggest that this ratio may be of physiological significance. C1 NCI,ROCKVILLE,MD. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD 21218. RP MARGOLIS, SA (reprint author), NATL INST STAND & TECHNOL,BLDG 222,ROOM A158,QUINCE ORCHARD RD,GAITHERSBURG,MD 20899, USA. FU NCI NIH HHS [Y01-CP9-0506] NR 24 TC 23 Z9 23 U1 0 U2 1 PU AMER SOC CLIN NUTRITION INC PI BETHESDA PA 9650 ROCKVILLE PIKE SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 1991 VL 54 IS 6 SU S BP S1315 EP S1318 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA GU397 UT WOS:A1991GU39700039 PM 1962589 ER PT J AU PETERKOFSKY, B AF PETERKOFSKY, B TI ASCORBATE REQUIREMENT FOR HYDROXYLATION AND SECRETION OF PROCOLLAGEN - RELATIONSHIP TO INHIBITION OF COLLAGEN-SYNTHESIS IN SCURVY SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT CONF ON ASCORBIC ACID : BIOLOGIC FUNCTIONS AND RELATION TO CANCER CY SEP 10-12, 1990 CL NIH, BETHESDA, MD SP NCI, NIDDKD HO NIH DE COLLAGEN; PROTEOGLYCAN; SCURVY; ASCORBATE; INSULIN-LIKE GROWTH FACTORS ID MESSENGER-RNA LEVELS; HUMAN-SKIN FIBROBLASTS; EMBRYO LIMB BONE; GROWTH FACTOR-I; PROLINE HYDROXYLATION; PROLYL HYDROXYLASE; GUINEA-PIG; VITAMIN-C; CULTURED FIBROBLASTS; ACID AB Vitamin C deficiency is associated with defective connective tissue, particularly in wound healing. Ascorbate is required for hydroxylation of proline residues in procollagen and hydroxyproline stabilizes the collagen triple helical structure. Consequently, ascorbate stimulates procollagen secretion. However, collagen synthesis in ascorbate-deficient guinea pigs is decreased with only moderate effects on proline hydroxylation. Proteoglycan synthesis, which does not require ascorbate, also is decreased and both effects are correlated with the extent of weight loss during scurvy. Fasting, with ascorbate supplementation, produces similar effects. Both functions are inhibited in cells cultured in sera from either scorbutic or starved guinea pigs and inhibition is reversed with insulin-like growth factor (IGF)-I. The inhibitor appears to consist of two IGF-binding proteins induced during vitamin C deficiency and starving and may be responsible for in vivo inhibition of collagen and proteoglycan synthesis. RP PETERKOFSKY, B (reprint author), NCI,BIOCHEM LAB,BLDG 37,ROOM 4C-18,BETHESDA,MD 20892, USA. NR 54 TC 180 Z9 183 U1 7 U2 18 PU AMER SOC CLIN NUTRITION INC PI BETHESDA PA 9650 ROCKVILLE PIKE SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 1991 VL 54 IS 6 SU S BP S1135 EP S1140 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA GU397 UT WOS:A1991GU39700006 ER PT J AU STADTMAN, ER AF STADTMAN, ER TI ASCORBIC-ACID AND OXIDATIVE INACTIVATION OF PROTEINS SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT CONF ON ASCORBIC ACID : BIOLOGIC FUNCTIONS AND RELATION TO CANCER CY SEP 10-12, 1990 CL NIH, BETHESDA, MD SP NCI, NIDDKD HO NIH DE MIXED-FUNCTION OXIDATION SYSTEMS; PROTEIN OXIDATION; METAL ION CATALYSIS; OXYGEN FREE RADICALS; ASCORBATE; PROOXIDANT ACTIVITY; PROTEINS; METAL-CATALYZED OXIDATION; ENZYME INACTIVATION ID MIXED-FUNCTION OXIDATION; METAL-CATALYZED OXIDATION; RED BLOOD-CELLS; GLUTAMINE-SYNTHETASE; DENATURED PROTEINS; ESCHERICHIA-COLI; OXYGEN RADICALS; ALKALINE-PHOSPHATASE; ENZYMATIC-ACTIVITY; METABOLIC ENZYMES AB A number of active oxygen species are likely, implicated in the etiology or manifestation of several pathological conditions, including aging, arthritis, carcinogenesis, atherosclerosis, and muscular dystrophy. Ascorbate plays a key role in protecting cells against oxidative damage. Paradoxically, in the presence of Fe3+ or Cu2+, ascorbate can promote the generation of the same reactive oxygen species (.OH, O2-, H2O2, and ferryl ion) it is known to destroy. This prooxidant activity derives from the ability of ascorbate to reduce Fe2+ or Cu2+ to Fe2+ or Cu+, respectively, and to reduce O2 to O2 approximately-equal-to and H2O2. Damage to nucleic acid and proteins results from the binding of either Fe2+ or Cu+ to metal binding sites on these macromolecules followed by reaction of the metal complexes with H2O2; this leads to the production of active oxygen species that attack functional groups at or near the metal binding sites. RP STADTMAN, ER (reprint author), NHLBI,BIOCHEM LAB,9000 ROCKVILLE PIKE,BLDG 3,ROOM 222,BETHESDA,MD 20892, USA. NR 57 TC 88 Z9 88 U1 2 U2 4 PU AMER SOC CLIN NUTRITION INC PI BETHESDA PA 9650 ROCKVILLE PIKE SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 1991 VL 54 IS 6 SU S BP S1125 EP S1128 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA GU397 UT WOS:A1991GU39700004 PM 1962558 ER PT J AU WASHKO, P ROTROSEN, D LEVINE, M AF WASHKO, P ROTROSEN, D LEVINE, M TI ASCORBIC-ACID IN HUMAN NEUTROPHILS SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT CONF ON ASCORBIC ACID : BIOLOGIC FUNCTIONS AND RELATION TO CANCER CY SEP 10-12, 1990 CL NIH, BETHESDA, MD SP NCI, NIDDKD HO NIH DE ASCORBIC ACID; DEHYDROASCORBIC ACID; HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY; GLUCOSE; NEUTROPHILS ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; COULOMETRIC ELECTROCHEMICAL DETECTION; PERFORMANCE LIQUID-CHROMATOGRAPHY; CHROMAFFIN CELLS; DIABETES-MELLITUS; TRANSPORT; GLUCOSE; PLASMA; ACCUMULATION; STIMULATION AB The uptake and distribution of ascorbic acid and the effect of extracellular glucose on ascorbic acid transport were investigated in human neutrophils. Freshly isolated neutrophils contained 1.0-1.4 mmol ascorbic acid/L, at least 94% of which was present unbound in the cytosol. Intracellular ascorbic acid was found only in the reduced form. The presence of physiologic amounts of ascorbic acid in the extracellular buffer led to the accumulation of millimolar concentrations of ascorbic acid intracellularly. Accumulation was mediated by a high- and a low-affinity transport activity. The high-affinity transport activity had an apparent K(m) of 2-5-mu-mol/L whereas the low-affinity transport activity had an apparent K(m) of 6-7 mmol/L. Glucose inhibited the uptake and accumulation of ascorbic acid by both transport activities in a concentration-dependent fashion. Glucose-induced inhibition of both ascorbic acid transport activities was completely reversible. C1 NIDDKD,CELL BIOL & GENET LAB,BLDG 8,ROOM 415,BETHESDA,MD 20892. NIAID,HOST DEF LAB,BETHESDA,MD 20892. RP LEVINE, M (reprint author), NIDDKD,CELL BIOL & GENET LAB,BLDG 8,ROOM 415,BETHESDA,MD 20892, USA. NR 45 TC 47 Z9 48 U1 0 U2 1 PU AMER SOC CLIN NUTRITION INC PI BETHESDA PA 9650 ROCKVILLE PIKE SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 1991 VL 54 IS 6 SU S BP S1221 EP S1227 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA GU397 UT WOS:A1991GU39700022 ER PT J AU HERRERO, R POTISCHMAN, N BRINTON, LA REEVES, WC BRENES, MM TENORIO, F DEBRITTON, RC GAITAN, E AF HERRERO, R POTISCHMAN, N BRINTON, LA REEVES, WC BRENES, MM TENORIO, F DEBRITTON, RC GAITAN, E TI A CASE-CONTROL STUDY OF NUTRIENT STATUS AND INVASIVE CERVICAL-CANCER .1. DIETARY INDICATORS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE CAROTENE; CERVIX NEOPLASMS; DIET; FOLIC ACID; VITAMIN-A; VITAMIN-C ID VITAMIN-A; LATIN-AMERICA; RISK; DYSPLASIA; PLASMA; EPIDEMIOLOGY; RETINOIDS; NEOPLASIA; FREQUENCY; SMOKING AB A study of 748 cases and 1,411 hospital and community controls in four Latin American countries evaluated the association between certain elements of diet and invasive cervical cancer. Subjects were interviewed about their adult consumption of 58 food items, including the major sources of putative protective agents (vitamin A, carotenoids, vitamin C, and folacin) as well as other behavioral and medical characteristics related to cervical cancer. Participation rates were above 95% for both cases and controls. After adjustment for age, study site, sexual and reproductive behavior, socioeconomic status, screening practices, and detection of human papillomavirus 16/18 by filter in situ hybridization, a slightly lower risk was observed for the highest quartiles of consumption of fruit and fruit juices, while no reductions in risk were associated with vegetables, foods of animal origin, complex carbohydrates, legumes, or folacin-rich foods. When nutrient indices were derived, significant trends of decreasing risk were observed for vitamin C (adjusted odds ratio (OR) = 0.69 for the highest vs. the lowest quartile; p for trend = 0.003), beta-carotene (OR = 0.68; p = 0.02), and other carotenoids (OR = 0.61; p = 0.003). Inclusion of vitamin C and beta-carotene in the same model attenuated the association with beta-carotene, while the association with vitamin C remained unchanged. The results are consistent with those of other investigations and provide support for a protective effect of vitamin C, carotenoids, and other substances found in the same fruits and vegetables against the development of invasive cervical cancer. However, the fact that the associations were driven by relation in two of the study sites and among women of higher socioeconomic status leaves open the possibility of selection bias or effects of unidentified aspects of dietary patterns. C1 NCI,ENVIRONM EPIDEMIOL BRANCH,EXECUT PLAZA NORTH,ROOM 443,BETHESDA,MD 20892. UNIDAD NACL CANCEROL,CAJA COSTARRICENSE SEGURO SOCIAL,SAN JOSE,COSTA RICA. GORGAS MEM LAB,PANAMA CITY,PANAMA. HOSP ONCOL NACL,INST MEXICANO SEGURIDAD SOCIAL,MEXICO CITY,MEXICO. INST ONCOL NACL,PANAMA CITY,PANAMA. INST NACL CANCEROL,DIV EPIDEMIOL,BOGOTA,COLOMBIA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU NCI NIH HHS [N01-CP-41026, R01-CA-42042] NR 43 TC 79 Z9 81 U1 0 U2 3 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 DEC 1 PY 1991 VL 134 IS 11 BP 1335 EP 1346 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GX680 UT WOS:A1991GX68000010 PM 1755447 ER PT J AU POTISCHMAN, N HERRERO, R BRINTON, LA REEVES, WC STACEWICZESAPUNTZAKIS, M JONES, CJ BRENES, MM TENORIO, F DEBRITTON, RC GAITAN, E AF POTISCHMAN, N HERRERO, R BRINTON, LA REEVES, WC STACEWICZESAPUNTZAKIS, M JONES, CJ BRENES, MM TENORIO, F DEBRITTON, RC GAITAN, E TI A CASE-CONTROL STUDY OF NUTRIENT STATUS AND INVASIVE CERVICAL-CANCER .2. SEROLOGIC INDICATORS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE CAROTENE; CERVIX NEOPLASMS; SEROLOGY; VITAMIN-A; VITAMIN-E ID MIDDLE-AGED MEN; VITAMIN-A; ALPHA-TOCOPHEROL; BETA-CAROTENE; SERUM LEVELS; DIET; RETINOL; RESPONSES; SMOKING; WOMEN AB A study of 387 cases and 670 controls from four Latin American countries evaluated the hypothesis that lower serum levels of eight micronutrients were associated with a higher risk of invasive cervical cancer. The serologic analyses were restricted to a sample of subjects with stage I and II disease to minimize effects of the disease on the serologic markers. Ninety-four percent of eligible subjects donated blood samples, which were analyzed for carotenoids, retinol, and tocopherols by high-pressure liquid chromatography. Cases did not differ significantly from controls in mean serum levels of retinol, cryptoxanthin, lycopene, alpha-carotene, lutein, or alpha-tocopherol. The mean level of beta-carotene was lower and the mean level of gamma-tocopherol was higher among cases as compared with controls. After adjustment for age, study site, sexual and reproductive behavior, socioeconomic status, screening practices, detection of human papillomavirus types 16/18, cholesterol, and triglycerides, a trend of decreasing risk was associated with higher levels of beta-carotene (p for trend = 0.05), with the adjusted odds ratio decreasing to 0.72 for the highest versus the lowest quartile. beta-Carotene results were similar by stage of disease, which argues against an effect of disease progression on nutrient values. Unexpectedly, increasing risks were observed as the level of gamma-tocopherol increased (odds ratio = 2.09; p for trend = 0.03); however, levels were higher among stage II cases as compared with stage I cases, suggesting a metabolic alteration resulting from the disease process. The concordance in the strength and direction of the blood and dietary results, presented in the accompanying report (Herrero R, Potischman N, Brinton LA, et al., American Jouranl of Epidemiology 1991; 134:1335-46), supports a role for beta-carotene or foods rich in beta-carotene in the etiology of cervical cancer. This study also indicates that simultaneous analysis using serologic and dietary nutrient indicators allows better discrimination of the association. C1 UNIDAD NACL CANCEROL,CAJA COSTARRICENSE SEGURO SOCIAL,SAN JOSE,COSTA RICA. GORGAS MEM LAB,PANAMA CITY,PANAMA. UNIV ILLINOIS,DEPT NUTR & MED DIETET,CHICAGO,IL 60680. OCCUPAT SAFETY & HLTH ADM,HLTH STAND PROGRAM,WASHINGTON,DC. HOSP ONCOL NACL,INST MEXICANO SEGURIDAD SOCIAL,MEXICO CITY,MEXICO. INST ONCOL NACL,PANAMA CITY,PANAMA. INST NACL CANCEROL,DIV EPIDEMIOL,BOGOTA,COLOMBIA. RP POTISCHMAN, N (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,EXECUT PLAZA NORTH,ROOM 443,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 27 TC 68 Z9 70 U1 0 U2 2 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 1 PY 1991 VL 134 IS 11 BP 1347 EP 1355 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GX680 UT WOS:A1991GX68000011 PM 1755448 ER PT J AU FRANKENFIELD, DL REYNOLDS, DR REGINA, DA AF FRANKENFIELD, DL REYNOLDS, DR REGINA, DA TI PHARMACIST-INITIATED POISON PREVENTION CAMPAIGN IN A RURAL-COMMUNITY SO AMERICAN JOURNAL OF HOSPITAL PHARMACY LA English DT Note ID PROGRAM C1 TOHATCHI HLTH CTR,PHARM SERV,TOHATCHI,NM. REHOBOTH MCKINLEY CHRISTIAN HOSP,GALLUP,NM. RP FRANKENFIELD, DL (reprint author), NIDA,ADDICT RES CTR,DEPT PHARM,PHARM SERV,POB 5180,4940 EASTERN BLDG C,BALTIMORE,MD 21224, USA. NR 7 TC 5 Z9 5 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 DEC PY 1991 VL 48 IS 12 BP 2657 EP 2658 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GR456 UT WOS:A1991GR45600029 PM 1814216 ER PT J AU MINOR, JR HAMBURG, MA AF MINOR, JR HAMBURG, MA TI THE AIDS RESEARCH AGENDA AT THE NATIONAL-INSTITUTES-OF-HEALTH SO AMERICAN JOURNAL OF HOSPITAL PHARMACY LA English DT Article DE ACQUIRED IMMUNODEFICIENCY SYNDROME; ACQUIRED IMMUNODEFICIENCY SYNDROME VACCINES; ADMINISTRATION; ANTIVIRALS; DRUG INFORMATION; HIV INFECTIONS; INFORMATION; NATIONAL-INSTITUTES-OF-HEALTH; PHARMACISTS; RESEARCH AB The foundation, goals, and components of the research strategy developed by the National Institutes of Health to combat AIDS and HIV infection are discussed. The AIDS research agenda, based on systems originally designed to coordinate cancer research, involves a national effort to study various aspects of the disease, disseminate information, and rapidly develop and test drugs and vaccines to treat and prevent AIDS and HIV disease. AIDS research makes up approximately 10% of the total NIH budget of $7.6 billion, and the largest portion of that allocation goes to improving current treatments and developing new agents. Drug discovery efforts are supported by the National Institute of Allergy and Infectious Diseases (NIAID) through the Division of Intramural Research, in which biomedical and clinical research is conducted, and the Division of AIDS, which coordinates extramural research in university-based centers and community programs. By providing educational materials and sponsoring conferences, NIAID also helps to disseminate the results of the research it coordinates. Pharmacists support AIDS research through their involvement with study drug products and their role in protocol development, regulatory affairs, product development, and accumulation and distribution of drug information. Research initiatives sponsored by the federal government combine resources of investigators from government, academia, and the pharmaceutical and biotechnological industries to meet the challenges posed by the AIDS epidemic. C1 NEW YORK CITY DEPT HLTH,FAMILY HLTH SERV,NEW YORK,NY 10013. RP MINOR, JR (reprint author), NIH,CTR CLIN,DEPT PHARM,BLDG 10,ROOM 1 N257,BETHESDA,MD 20892, USA. NR 0 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 DEC PY 1991 VL 48 IS 12 BP 2662 EP 2666 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GR456 UT WOS:A1991GR45600031 PM 1667566 ER PT J AU MARTINEZ, M GOLDIN, LR AF MARTINEZ, M GOLDIN, LR TI DETECTION OF LINKAGE FOR HETEROGENEOUS DISORDERS BY USING MULTIPOINT LINKAGE ANALYSIS SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENETIC-HETEROGENEITY; STRATEGIES; HUMANS; POWER AB We have compared the efficiency of the lod score test which assumes heterogeneity (lod2) to the standard lod score test which assumes homogeneity (lod1) when three-point linkage analysis is used in successive map intervals. If it is assumed that a gene located midway between two linked marker loci is responsible for a proportion of disease cases, then the lod1 test loses power relative to the lod2 test, as the proportion of linked families decreases, as the flanking markers are more closely linked, and as more map intervals are tested. Moreover, when multipoint analysis is used, linkage for a disease gene is more likely to be incorrectly excluded from a complete and dense linkage map if true genetic heterogeneity is ignored. We thus conclude that, in general, the lod2 linkage test is more efficient for detecting a true linkage when a complete genetic marker map is screened for a heterogeneous disorder. C1 NIMH,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. RP MARTINEZ, M (reprint author), INSERM,U155,UNITE RECH GENET EPIDEMIOL,CHATEAU LONGCHAMPS,F-75005 PARIS,FRANCE. RI Martinez, Maria/B-3111-2013 OI Martinez, Maria/0000-0003-2180-4537 NR 12 TC 11 Z9 11 U1 0 U2 1 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 DEC PY 1991 VL 49 IS 6 BP 1300 EP 1305 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA GU672 UT WOS:A1991GU67200016 PM 1684087 ER PT J AU HUANG, THM HEJTMANCIK, JF EDWARDS, A PETTIGREW, AL HERRERA, CA HAMMOND, HA CASKEY, CT ZOGHBI, HY LEDBETTER, DH AF HUANG, THM HEJTMANCIK, JF EDWARDS, A PETTIGREW, AL HERRERA, CA HAMMOND, HA CASKEY, CT ZOGHBI, HY LEDBETTER, DH TI LINKAGE OF THE GENE FOR AN X-LINKED MENTAL-RETARDATION DISORDER TO A HYPERVARIABLE (AGAT)N REPEAT MOTIF WITHIN THE HUMAN HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE (HPRT) LOCUS (XQ26) SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID FORSSMAN-LEHMANN SYNDROME; HUMAN GENOME; POLYMORPHISMS; DNA; LOCALIZATION; CHROMOSOME; FREQUENCY; COMMITTEE AB We recently reported a new X-linked mental retardation (XLMR) disorder in a four-generation family of Dutch descent. Features included Dandy-Walker malformation, basal ganglia disease, and seizures. Twenty-six family members, including two living affected males and two obligate carriers, were available for study. No evidence of linkage was observed between the disease locus and RFLPs from several X-chromosome regions, including Xp21-p22 (13 markers), proximal Xq (four markers), and Xq28 (three markers). However, a new hypervariable short tandem repeat (STR) within the HPRT gene at Xq26 showed positive linkage to the disease locus, with a maximum lod score of 2.19 at a recombination fraction of 0. A second hypervariable marker in Xq26, the dinucleotide repeat XL90A3 (DXS425), showed a lod score of .84 at a recombination fraction of .11. Both the HPRT and DXS425 markers were typed in 40 CEPH families, and subsequent multipoint linkage analysis showed the following order: Xcen-DXS425-(HPRT,XLMR)-F9-qter. HPRT and these flanking markers are therefore useful for carrier detection and prenatal diagnosis in this family. This study illustrates that hypervariable STRs will be powerful tools for linkage analysis and genetic diagnosis, particularly when relatively small families are involved. C1 BAYLOR COLL MED,INST MOLEC GENET,1 BAYLOR PLAZA,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. BAYLOR COLL MED,HOWARD HUGHES MED INST,HOUSTON,TX 77030. NEI,BETHESDA,MD 20892. RP LEDBETTER, DH (reprint author), BAYLOR COLL MED,INST MOLEC GENET,1 BAYLOR PLAZA,HOUSTON,TX 77030, USA. FU NIDDK NIH HHS [DK 31428] NR 26 TC 40 Z9 40 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 DEC PY 1991 VL 49 IS 6 BP 1312 EP 1319 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA GU672 UT WOS:A1991GU67200018 PM 1746558 ER PT J AU STRIKER, GE AF STRIKER, GE TI HIGHLIGHTS OF FISCAL YEAR 1992 RESEARCH INITIATIVES SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Editorial Material RP STRIKER, GE (reprint author), NIDDKD,DIV KIDNEY UROL & HEMATOL DIS,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD DEC PY 1991 VL 18 IS 6 BP 700 EP 701 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA GT961 UT WOS:A1991GT96100012 PM 1962656 ER PT J AU LAWRENCE, JB FRIEDMAN, BS TRAVIS, WD CHINCHILLI, VM METCALFE, DD GRALNICK, HR AF LAWRENCE, JB FRIEDMAN, BS TRAVIS, WD CHINCHILLI, VM METCALFE, DD GRALNICK, HR TI HEMATOLOGIC MANIFESTATIONS OF SYSTEMIC MAST-CELL DISEASE - A PROSPECTIVE-STUDY OF LABORATORY AND MORPHOLOGICAL FEATURES AND THEIR RELATION TO PROGNOSIS SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID BONE-MARROW; LYMPHOPROLIFERATIVE DISORDERS; URTICARIA PIGMENTOSA; ACUTE-LEUKEMIA; MASTOCYTOSIS; HISTAMINE; SKIN; FIBROBLASTS; PRECURSORS; CULTURE AB PURPOSE: Systemic mast cell disease (SMCD) follows an indolent course in most patients, but a significant number of patients die of neoplastic hematologic disorders. Reviews of the literature and retrospective studies in a single institution have defined features that may be associated with a poor prognosis, but prospective studies have been lacking. Therefore, we prospectively analyzed the relationship between clinical, laboratory, and hematopathologic findings and clinical outcome in a series of 46 patients with mast cell disease. This analysis was employed to both define clinically useful prognostic variables and describe the histologic evolution of bone marrow mast cell infiltration and its relationship to hematologic neoplasia. PATIENTS AND METHODS: Forty-six adult patients were referred to the National Institutes of Health (NIH) with clinical and/or pathologic evidence of mast cell proliferation. All patients had bone marrow examinations, and 10 patients underwent serial bone marrow biopsies. The diagnosis of SMCD required pathologic documentation of bone marrow mast cell infiltrates. The patients were followed for up to 13 years at the NIH (up to 30 years after the initial pathologic diagnosis of mast cell disease). Statistical analysis defined the correlation between variables and the presence of diagnostic bone marrow lesions. The Kaplan-Meier method was used to construct survival curves, and the effects of various variables on the survival time were examined. RESULTS: Thirty-two of 46 patients (74%) had a bone marrow biopsy diagnostic for SMCD. The remaining 14 patients were considered to have cutaneous mast cell disease (CMCD). Univariate analysis showed that hepatosplenomegaly, alkaline phosphatase level, absolute lymphocyte count, and age at onset of symptoms were positively correlated with SMCD, whereas hemoglobin level was negatively associated with diagnostic bone marrow lesions. With multivariate analysis, only hemoglobin and absolute lymphocyte count remained as significant independent predictors of bone marrow findings. No CMCD patient died or had significant clinical deterioration in the 1- to 30-year period of follow-up (median = 8.5 years), whereas 10 of 32 SMCD patients (31%) died from 1 to 22 years after diagnosis (median = 2.5 years) (p < 0.0001). Univariate analysis revealed the following variables as significantly increasing the risk of death in patients with SMCD: later onset of symptoms, absence of cutaneous mastocytosis, thrombocytopenia, elevated lactate dehydrogenase (LDH) level, anemia, bone marrow hypercellularity, qualitative peripheral blood smear abnormalities, elevated alkaline phosphatase level, and hepatosplenomegaly. Multivariate analysis showed that only the age at onset of symptoms and LDH levels were significant independent predictors of survival. Eight of the 10 SMCD patients who died had myeloproliferative or myelodysplastic syndromes or acute nonlymphocytic leukemia. CONCLUSION: Our prospective study has defined a number of important variables in patients with clinical evidence of mast cell proliferation that can predict both the presence of SMCD and the likelihood of fatal disease. Since recent evidence suggests that mast cells derive from a bone marrow hematopoietic progenitor, SMCD may represent a myeloproliferative condition with the propensity to evolve into a neoplastic granulocytic disorder in a significant minority of patients. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PATHOL,RICHMOND,VA 23298. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT BIOSTAT,RICHMOND,VA 23298. NIAID,CTR CLIN,DEPT CLIN PATHOL,HEMATOL SERV,BETHESDA,MD 20892. NIAID,CLIN INVEST LAB,MAST CELL PHYSIOL SECT,BETHESDA,MD 20892. NR 46 TC 137 Z9 139 U1 0 U2 1 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 DEC PY 1991 VL 91 IS 6 BP 612 EP 624 DI 10.1016/0002-9343(91)90214-I PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA GW375 UT WOS:A1991GW37500009 PM 1750431 ER PT J AU FRIEDMAN, TC THOMAS, PM FLEISHER, TA FEUILLAN, P PARKER, RI CASSORLA, F CHROUSOS, GP AF FRIEDMAN, TC THOMAS, PM FLEISHER, TA FEUILLAN, P PARKER, RI CASSORLA, F CHROUSOS, GP TI FREQUENT OCCURRENCE OF ASPLENISM AND CHOLELITHIASIS IN PATIENTS WITH AUTOIMMUNE POLYGLANDULAR DISEASE TYPE-I SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID SPLENIC FUNCTION; CANDIDIASIS; CHOLESTEROL; SECRETION; MOTILITY; ATROPHY; BILE; RISK AB PURPOSE: This study assesses the occurrence of asplenism and gallstones in patients with auto-immune polyglandular disease type I (APG I). PATIENTS AND METHODS: Nine patients with APG I (ages 14 to 48) were studied at the National Institutes of Health. Each patient received endocrine testing, a careful examination of his or her peripheral blood smear, lymphocyte immunophenotyping, a liver-spleen scan, and either an upper abdominal ultrasound or a computer-assisted tomogram to evaluate the spleen and gallbladder. RESULTS: We documented asplenism in four patients and cholelithiasis in four patients, with two patients having both conditions. The patients with asplenism had Howell-Jolly bodies on peripheral blood smears, lack of splenic uptake by liver-spleen scan, and absent spleens by abdominal computed tomographic scan or ultrasound evaluation. The clinical presentation of the patients with cholelithiasis ranged from acute symptoms requiring surgery to asymptomatic gallstones. Lymphocyte immunophenotyping did not reveal consistent changes in either B- or T-cell subpopulations in the patients studied. CONCLUSION: Asplenism and gallstones occur frequently in patients with APG I. In addition to careful examination of the peripheral blood smear for Howell-Jolly bodies to screen for asplenism, we recommend an abdominal ultrasound to detect asplenism and/or gallstones in all patients with APG I. Appropriate immunizations and antibiotic coverage may be helpful in those patients with absent spleens. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. NIH,CTR CLIN,IMMUNOL SERV,BETHESDA,MD 20892. NIH,CTR CLIN,HEMATOL SERV,BETHESDA,MD 20892. RP FRIEDMAN, TC (reprint author), NICHHD,DEV NEUROBIOL LAB,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N262,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 33 TC 37 Z9 37 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 DEC PY 1991 VL 91 IS 6 BP 625 EP 630 DI 10.1016/0002-9343(91)90215-J PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA GW375 UT WOS:A1991GW37500010 PM 1750432 ER PT J AU SMITH, LH DRACH, G HALL, P LINGEMAN, J PREMINGER, G RESNICK, MI SEGURA, JW AF SMITH, LH DRACH, G HALL, P LINGEMAN, J PREMINGER, G RESNICK, MI SEGURA, JW TI NATIONAL HIGH BLOOD-PRESSURE EDUCATION-PROGRAM (NHBPEP) REVIEW PAPER ON COMPLICATIONS OF SHOCK-WAVE LITHOTRIPSY FOR URINARY CALCULI SO AMERICAN JOURNAL OF MEDICINE LA English DT Review ID KIDNEY; HYPERTENSION; REMOVAL; SURGERY; STONES AB This decade has witnessed dramatic advances in the surgical management of urinary calculi. Today, most stones can be removed by minimally invasive means. In fact, the treatment of choice in 60% to 90% of patients with renal and ureteral calculi that need to be surgically removed is extracorporeal shock wave lithotripsy (ESWL). This article reviews indications for ESWL and discusses deleterious effects of ESWL. C1 NIH,NATL HIGH BLOOD PRESSURE EDUC PROGRAM,BETHESDA,MD 20892. MAYO MED SCH & CLIN,DIV UROL,ROCHESTER,MN. UNIV ARIZONA,ARIZONA MED CTR,TUCSON,AZ 85724. CLEVELAND CLIN,DIV HYPERTENS & NEPHROL,CLEVELAND,OH 44106. METHODIST HOSP INDIANA,INST KIDNEY STONE DIS,INDIANAPOLIS,IN 46202. UNIV TEXAS,HLTH SCI CTR,SW MED SCH,DIV UROL,DALLAS,TX 75235. CASE WESTERN RESERVE UNIV,DIV UROL,CLEVELAND,OH 44106. MAYO MED SCH & CLIN,DIV NEPHROL,ROCHESTER,MN. NR 50 TC 24 Z9 24 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 DEC PY 1991 VL 91 IS 6 BP 635 EP 641 DI 10.1016/0002-9343(91)90217-L PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA GW375 UT WOS:A1991GW37500012 PM 1750434 ER PT J AU ISADA, NB PAAR, DP JOHNSON, MP EVANS, MI HOLZGREVE, W QURESHI, F STRAUS, SE AF ISADA, NB PAAR, DP JOHNSON, MP EVANS, MI HOLZGREVE, W QURESHI, F STRAUS, SE TI INUTERO DIAGNOSIS OF CONGENITAL VARICELLA ZOSTER VIRUS-INFECTION BY CHORIONIC VILLUS SAMPLING AND POLYMERASE CHAIN-REACTION SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 38TH ANNUAL MEETING OF THE SOC FOR GYNECOLOGIC INVESTIGATION CY MAR 20-23, 1991 CL SAN ANTONIO, TX SP SOC GYNECOL INVESTIGAT DE CHORIONIC VILLUS SAMPLING; POLYMERASE CHAIN REACTION; VARICELLA ZOSTER VIRUS ID HUMAN IMMUNODEFICIENCY VIRUS; PRENATAL-DIAGNOSIS; DNA; PARVOVIRUS AB Varicella zoster virus infection acquired in pregnancy is reported to cause fetal damage in 5% to 10% of cases. We used polymerase chain reaction to attempt molecular diagnosis of fetoplacental varicella zoster virus infection in two patients. Tissue obtained by chorionic villus sampling in the second trimester was analyzed by polymerase chain reaction with a varicella zoster virus-specific primer, ORF-63, and was found to be positive in both patients. Viral cultures were negative. One patient elected pregnancy termination at 23 weeks. Southern blot hybridization of neonatal brain tissue for varicella zoster virus was negative. The second patient carried the pregnancy to term and was delivered of a normal infant. Varicella zoster virus immunoglobulin M and viral cultures were negative. The presence of viral deoxyribonucleic acid sequences in placental tissue does not correlate with fetal disease. C1 WAYNE STATE UNIV,HUTZEL HOSP,DEPT PATHOL,DETROIT,MI 48201. WAYNE STATE UNIV,HUTZEL HOSP,DEPT MOLEC BIOL & GENET,DETROIT,MI 48201. NIAID,CLIN INVEST LAB,MED VIROL SECT,BETHESDA,MD 20892. INST HUMAN GENET & ANTHROPOL,MUNSTER,GERMANY. RP ISADA, NB (reprint author), WAYNE STATE UNIV,HUTZEL HOSP,DEPT OBSTET & GYNECOL,DIV REPROD GENET,4707 ST ANTOINE,DETROIT,MI 48201, USA. NR 16 TC 31 Z9 31 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 1991 VL 165 IS 6 BP 1727 EP 1730 PN 1 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA GX844 UT WOS:A1991GX84400022 PM 1661069 ER PT J AU WEICH, HA SALAHUDDIN, SZ GILL, P NAKAMURA, S GALLO, RC FOLKMANN, J AF WEICH, HA SALAHUDDIN, SZ GILL, P NAKAMURA, S GALLO, RC FOLKMANN, J TI AIDS-ASSOCIATED KAPOSIS SARCOMA-DERIVED CELLS IN LONG-TERM CULTURE EXPRESS AND SYNTHESIZE SMOOTH-MUSCLE ALPHA-ACTIN SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Note ID GROWTH FACTOR-I; FACTOR A-CHAIN; MESSENGER-RNAS; B-CHAIN; ENDOTHELIAL-CELLS; TRANSFORMING GENE; SEQUENCE; PDGF; MYOFIBROBLASTS; ONCOGENE AB Spindle-shaped cells from Kaposi's sarcoma lesions (AIDS-KS cells) were cultured for long periods in the presence of conditioned medium from activated CD4-positive T cells (HTLV-II infected transformed nonvirus producer) and characterized under in vitro conditions. To investigate a possible vascular origin, AIDS-KS cells were analyzed for the presence of smooth muscle alpha-actin, a differentiation marker for vascular smooth muscle cells. Immunofluorescence studies using a monoclonal antibody for smooth muscle alpha-actin demonstrated positive staining of the AIDS-KS cells (KS-3 and KS-4) but not by endothelial cells or fibroblasts. Northern blot analysis using an oligonucleotide probe unique for human smooth muscle alpha-actin indicated the expression of this gene by AIDS-KS cells. Similar analysis of biopsies from the KS lesion showed that in addition to the staining of smooth muscle cells associated with the blood vessels, the tumor-related spindle cells also stained positively. These cells were also analyzed for the expression of different growth factor genes. The platelet-derived growth factor (PDGF) A-chain gene was expressed at a moderate level. The insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-2 (IGF-2) genes were not overexpressed in relation to control cells. These data suggest that the analyzed AIDS-KS cells may be smooth muscle-like cells and therefore of vascular origin. Based on these results as well as previous reports, we speculate that cells of the immune system may regulate growth of cells in the vascular wall by a novel pathway. C1 NCI,TUMOR BIOL LAB,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT ANAT & CELLULAR BIOL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT SURG,BOSTON,MA 02115. UNIV SO CALIF,SCH MED,DEPT MED,LOS ANGELES,CA 90033. HUNTINGTON MEM HOSP,INST MOLEC MED & TECHNOL,PASADENA,CA 91105. FU NCI NIH HHS [R01-CA37395] NR 31 TC 67 Z9 67 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 1991 VL 139 IS 6 BP 1251 EP 1258 PG 8 WC Pathology SC Pathology GA GV794 UT WOS:A1991GV79400007 PM 1750501 ER PT J AU DAI, YS AMBUDKAR, IS HORN, VJ YEH, CK KOUSVELARI, EE WALL, SJ LI, M YASUDA, RP WOLFE, BB BAUM, BJ AF DAI, YS AMBUDKAR, IS HORN, VJ YEH, CK KOUSVELARI, EE WALL, SJ LI, M YASUDA, RP WOLFE, BB BAUM, BJ TI EVIDENCE THAT M3-MUSCARINIC-RECEPTORS IN RAT PAROTID-GLAND COUPLE TO 2 2ND MESSENGER SYSTEMS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE [H-3]QUINUCLIDINYL BENZILATE BINDING; MUSCARINIC RECEPTOR SUBTYPES; RECEPTOR COUPLING; CYTOSOLIC CALCIUM MOBILIZATION; INOSITOL TRISPHOSPHATE FORMATION; ADENOSINE 3',5'-CYCLIC MONOPHOSPHATE INHIBITION; IMMUNOCHEMISTRY; ANTIMUSCARINIC RECEPTOR ANTIBODIES; NORTHERN BLOTS ID ADENYLATE-CYCLASE INHIBITION; CHOLINERGIC RECEPTORS; CYCLIC-AMP; PHOSPHOINOSITIDE TURNOVER; BIOCHEMICAL-PROPERTIES; BINDING-PROPERTIES; ACINAR-CELLS; HYDROLYSIS; ACTIVATION; SUBTYPES AB The binding affinities of muscarinic antagonists were compared with their abilities to block carbachol (CCh)-mediated stimulation of Ca2+ mobilization and inhibition of isoproterenol-elicited adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in rat parotid cells. The binding of [H-3]quinuclidinyl benzilate (QNB) to membranes was inhibited by antagonists with the following potencies (dissociation constant, nM): atropine (1.1) almost-equal-to 4-diphenylacetoxy-N-methylpiperidine methbromide (4-DAMP) (1.6) >> pirenzepine (136) > 11-[[2-[(diethylamino)methyl-1-piperidinyl]-acetyl]acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]-benzodiazepine-6-one (AF-DX 116) (5,293). AF-DX 116 blocked Ca2+ mobilization and inhibition of cAMP accumulation with low affinities [inhibitory concentration at 50% (IC50) = 3150 and 6,528 nM, respectively], whereas 4-DAMP blocked these responses with considerably higher affinities (IC50 = 4.3 and 11.4 nM, respectively). Schild plots of 4-DAMP and AF-DX 116 antagonism of CCh-stimulated inositol trisphosphate accumulation showed inhibitor constant (K(i)) values of 0.85 and 1,585 nM, respectively, whereas Schild plots of 4-DAMP, AF-DX 116, and methoctramine antagonism of CCh-induced inhibition of cAMP accumulation showed K(i) values of 1.3, 1,585, and 2,754 nM, respectively. Preincubation of cells with 0.1 mM 3-isobutyl-1-methylxanthine did not prevent the capacity of CCh to inhibit cAMP accumulation. Pertussis toxin blocked the CCh-elicited and G(i)-mediated inhibition of cAMP formation. Northern blot analysis showed the presence of mRNA for the M3, but not for the M2, subtype in parotid gland. An immunochemical procedure using m1-m5 specific antibodies was performed in parotid membranes and showed that the m3 receptor accounts for 93% of precipitable receptors. These data suggest that M3 receptors in the rat parotid are coupled to both the stimulation of Ca2+ mobilization and the inhibition of cAMP accumulation. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BLDG 10,ROOM 1N-113,BETHESDA,MD 20892. UNIV PENN,DEPT PHARMACOL,PHILADELPHIA,PA 19104. GEORGETOWN UNIV,DEPT PHARMACOL,WASHINGTON,DC 20007. NR 53 TC 110 Z9 110 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD DEC PY 1991 VL 261 IS 6 BP C1063 EP C1073 PN 1 PG 11 WC Physiology SC Physiology GA GX685 UT WOS:A1991GX68500016 ER PT J AU SAAD, MF ALGER, SA ZURLO, F YOUNG, JB BOGARDUS, C RAVUSSIN, E AF SAAD, MF ALGER, SA ZURLO, F YOUNG, JB BOGARDUS, C RAVUSSIN, E TI ETHNIC-DIFFERENCES IN SYMPATHETIC NERVOUS SYSTEM-MEDIATED ENERGY-EXPENDITURE SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE RESTING METABOLIC RATE; CATECHOLAMINES; PIMA INDIANS ID BETA-ADRENERGIC-BLOCKADE; BROWN ADIPOSE-TISSUE; PLASMA NOREPINEPHRINE; GLUCOSE INFUSIONS; METABOLIC-RATE; PIMA-INDIANS; OBESITY; CATECHOLAMINES; THERMOGENESIS; CARBOHYDRATE AB The impact of sympathetic nervous system (SNS) activity on energy expenditure (EE) was evaluated in nondiabetic Caucasian and Pima Indian men while on a weight-maintenance diet using two approaches as follows. 1) The relationship between 24-h EE, measured in a respiratory chamber, and 24-h urinary norepinephrine was studied in 36 Caucasians [32 +/- 8 (SD) yr, 95 +/- 41 kg, 22 +/- 13% fat] and 33 Pimas (29 +/- 6 yr, 103 +/- 28 kg, 30 +/- 9% fat). There was no differnce between the two groups in 24-h EE (2,422 vs. 2,523 kcal/24 h) and in urinary norepinephrine (28 vs. 31-mu-g/24 h), even after adjusting for body size and composition. Twenty-four-hour EE correlated significantly with 24-h urinary norepinephrine in Caucasians (r = 0.78, P < 0.001) but not in Pimas (r = 0.03), independent of fat-free mass (FFM), fat mass, and age. 2) The effect of beta-adrenoceptor blockade with propranolol (120-mu-g/kg FFM bolus and 1.2-mu-g.kg FFM-1.min-1 for 45 min) on the resting metabolic rate (RMR) was evaluated in 36 Caucasians (30 +/- 6 yr, 103 +/- 36 kg, 25 +/- 11% fat) and 32 Pimas (28 +/- 6 yr, 100 +/- 34 kg, 27 +/- 10% fat). The RMR was similar in the two groups (2,052 vs. 1,973 kcal/24 h) even after adjustment for FFM, fat mass, and age and dropped significantly after propranolol infusion in Caucasians (-3.9%, P < 0.001) but not in Pimas (-0.8%, P = 0.07). The decrease in RMR correlated significantly with the RMR (adjusted for FFM, fat mass, and age) before propranolol infusion in Caucasians (r = -0.57, P < 0.001) but not in Pimas (r = -0.18, P = 0.35). In conclusion, SNS activity is a determinant of EE in Caucasian but not in Pima Indian men. C1 NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,PHOENIX,AZ 85014. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT MED,BOSTON,MA 02215. NR 34 TC 60 Z9 60 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD DEC PY 1991 VL 261 IS 6 BP E789 EP E794 PN 1 PG 6 WC Physiology SC Physiology GA GX685 UT WOS:A1991GX68500050 PM 1685070 ER PT J AU TERADA, Y MORIYAMA, T MARTIN, BM KNEPPER, MA GARCIAPEREZ, A AF TERADA, Y MORIYAMA, T MARTIN, BM KNEPPER, MA GARCIAPEREZ, A TI RT-PCR MICROLOCALIZATION OF MESSENGER-RNA FOR GUANYLYL CYCLASE-COUPLED ANF RECEPTOR IN RAT-KIDNEY SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE NEPHRON; GLOMERULUS; VASA-RECTA; MICRODISSECTION ID ATRIAL-NATRIURETIC-FACTOR; POLYMERASE CHAIN-REACTION; COLLECTING DUCT; PEPTIDE RECEPTOR; NEPHRON SEGMENTS; ANGIOTENSIN; CGMP; GENE AB Microlocalization of mRNA coding for the guanylyl cyclase-coupled atrial natriuretic factor (ANF) receptor was carried out in the rat kidney. We used a combination of reverse transcription and polymerase chain reaction (RT-PCR) in individual microdissected renal tubule segments, glomeruli, and vasa recta bundles. Relative quantitation of the resulting amplified cDNA utilized densitometry of autoradiograms from Southern blots probed with a specific P-32-labeled probe. Among renal tubule segments, the largest signal was found in the terminal inner medullary collecting duct (IMCD). Slightly smaller signals were found in the initial IMCD and in loop of Henle segments from the inner medulla. Readily detectable signals were also seen in the following segments (in descending order): cortical collecting duct, proximal convoluted tubule, medullary thick ascending limb, cortical thick ascending limb, distal convoluted tubule, and outer medullary collecting duct. Large signals were also detected in glomeruli and in vasa recta bundles from the inner stripe of the outer medulla. Based on these results, we conclude that 1) renal microlocalization of specific mRNAs coding for hormone receptors is feasible through application of the RT-PCR procedure in microdissected renal tubules and vascular elements, and 2) the gene for the guanylyl cyclase-coupled ANF receptor is broadly expressed along the nephron, raising the possibility that multiple sites of ANF action are present. C1 NHLBI, KIDNEY & ELECTROLYTE METAB LAB, BLDG 10, RM 6N307, BETHESDA, MD 20892 USA. NIMH, CLIN NEUROSCI BRANCH, BETHESDA, MD 20892 USA. NR 32 TC 93 Z9 93 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD DEC PY 1991 VL 261 IS 6 BP F1080 EP F1087 PN 2 PG 8 WC Physiology SC Physiology GA GX687 UT WOS:A1991GX68700116 ER PT J AU RIEVES, RD LUNDGREN, JD LOGUN, C WU, T SHELHAMER, JH AF RIEVES, RD LUNDGREN, JD LOGUN, C WU, T SHELHAMER, JH TI EFFECT OF PROTEIN-KINASE-C ACTIVATING AGENTS ON RESPIRATORY GLYCOCONJUGATE RELEASE FROM FELINE AIRWAYS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE PHORBOL 12-MYRISTATE 13-ACETATE; RESPIRATORY SECRETION; EICOSANOID METABOLISM ID CALCIUM MESSENGER SYSTEM; RAT PAROTID-GLAND; ARACHIDONIC-ACID; PHORBOL ESTER; PROSTAGLANDIN SYNTHESIS; SECRETION; CELLS; INVITRO; STIMULATION; METABOLISM AB Abnormal regulation of airway glycoprotein secretion may underlie many respiratory diseases. Experimental activation of the protein kinase C (PKC) family of cytosolic enzymes has been shown to induce a secretory response in many tissues. To estimate the effect of PKC activation on airway secretion, alteration in the amount of radiolabeled respiratory glycoconjugate (RGC) released into culture media was determined following feline airway explant exposure to PKC activating agents. Exposure to two known activators of PKC, phorbol 12-myristate 13-acetate (PMA) and mezerein (MEZ), resulted in profound increases in respiratory glycoconjugate release over a seven day experimental period. The response evolved over several hours and was dose dependent. Maximal RGC release, 90% above control, occurred 2 days after exposure to either PMA or MEZ. Pharmacological inhibition of the PKC effect using two PKC inhibitors, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine and sphingosine, resulted in dose-dependent antagonism of the maximal PMA (10(-7) M)-stimulated RGC release, suggesting altered PKC activity was responsible for augmenting RGC release. Since altered arachidonic acid metabolism has been implicated in mediating some PKC effects, eicosanoids were assayed in airway explant supernatants following PMA exposure. Enhanced release of both cyclooxygenase and lipoxygenase pathway products was detected by radioimmunoassay. Cotreatment of explants with PMA and an inhibitor of oxidative arachidonic acid metabolism, nordihydroguaiaretic acid, blocked RGC release. These data demonstrate prolonged augmentation of respiratory glycoconjugate release from airway explants following exposure to PKC-activating agents. C1 NIH,DEPT CRIT CARE MED,BLDG 10,7D43,BETHESDA,MD 20892. NR 34 TC 14 Z9 14 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 DEC PY 1991 VL 261 IS 6 BP L415 EP L423 PN 1 PG 9 WC Physiology SC Physiology GA GX685 UT WOS:A1991GX68500091 PM 1767862 ER PT J AU MILLER, DS PRITCHARD, JB AF MILLER, DS PRITCHARD, JB TI INDIRECT COUPLING OF ORGANIC ANION SECRETION TO SODIUM IN TELEOST (PARALICHTHYS-LETHOSTIGMA) RENAL TUBULES SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE MEMBRANE TRANSPORT; KIDNEY; PROXIMAL TUBULE; GLUTARATE; RENAL SECRETION; PARA-AMINOHIPPURATE; FLUORESCEIN; FLUORESCENCE MICROSCOPY; VIDEO IMAGING; SOUTHERN FLOUNDER; TELEOST FISH ID BASOLATERAL MEMBRANE-VESICLES; PARA-AMINOHIPPURATE; PROXIMAL TUBULE; RAT-KIDNEY; TRANSPORT; TOXICITY; ACIDS; NA+ AB Recent findings in both rat and crab indicate that renal accumulation of p-aminohippurate (PAH) across the basolateral membrane can be coupled indirectly to the Na gradient through PAH-glutarate exchange and Na/glutarate cotransport. However, the role of this mechanism in net transepithelial PAH secretion was not examined. Therefore, proximal tubules from Southern flounder kidney were used to assess both the presence of indirect coupling in the fish and its relationship to net secretion. [C-14]glutarate uptake by proximal tubular masses was concentrative, Na dependent, and Li inhibitable. Glutarate efflux from preloaded masses was stimulated by addition of PAH to the medium. Thus flounder tubules exhibited both Na/glutarate uptake and glutarate-PAH exchange. Furthermore, steady-state [H-3]PAH accumulation was increased 50% by 10-50-mu-M glutarate, and this increase was abolished by Li, indicating indirect coupling of PAH entry to Na. To determine whether indirect coupling affected net secretion as well as tissue accumulation, the steady-state accumulation of an anionic dye, fluorescein (FL), was measured in individual renal tubules by use of epifluorescence microscopy and video-image analysis. FL accumulated in tubules to levels that were 20-40 times higher than the medium. In most fish, luminal fluoresence was measurably higher than cellular, and uptake in both compartments was markedly reduced by PAH and Li. Moreover, FL accumulation in cells and lumina was increased by 70-100% when 50-mu-M glutarate was added to the bathing medium. Thus glutarate not only stimulated uphill FL entry into the cells, but also stimulated active secretion into the tubular lumen. C1 NIEHS, CELLULAR & MOLEC PHARMACOL LAB, COMPARAT MEMBRANE PHARMACOL SECT, RES TRIANGLE PK, NC 27709 USA. DUKE UNIV, MARINE LAB, BEAUFORT, NC 28516 USA. RP MILLER, DS (reprint author), NIEHS, CELLULAR & MOLEC PHARMACOL LAB, INTRACELLULAR REGULAT SECT, RES TRIANGLE PK, NC 27709 USA. NR 19 TC 52 Z9 52 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD DEC PY 1991 VL 261 IS 6 BP R1470 EP R1477 PN 2 PG 8 WC Physiology SC Physiology GA GX687 UT WOS:A1991GX68700079 ER PT J AU PRITCHARD, JB MILLER, DS AF PRITCHARD, JB MILLER, DS TI COMPARATIVE INSIGHTS INTO THE MECHANISMS OF RENAL ORGANIC ANION AND CATION SECRETION SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Review DE RENAL PROXIMAL TUBULE; CRUSTACEAN URINARY BLADDER; P-AMINOHIPPURATE; TETRAETHYLAMMONIUM; ACTIVE TRANSPORT; TUBULAR SECRETION; BRUSH-BORDER MEMBRANE; BASOLATERAL MEMBRANE; TRANSEPITHELIAL TRANSPORT; ENERGY COUPLING ID MICROVILLUS MEMBRANE-VESICLES; RABBIT PROXIMAL TUBULE; BOREALIS URINARY-BLADDER; ACID ACTIVE-TRANSPORT; SURVIVING FROG KIDNEY; BASOLATERAL MEMBRANE; URATE TRANSPORT; PARA-AMINOHIPPURATE; CANCER-BOREALIS; PAH TRANSPORT AB Comparative models have played a major role in defining the mechanisms that enable vertebrate proximal tubules to transport organic anions and cations from the peritubular interstitium to the urine. The unique advantages of these models and their contributions to our understanding of organic anion and cation transport mechanisms are summarized here. Recent studies of the organic anion transport system suggest that transport is coupled to metabolic energy via indirect coupling to the sodium gradient. Organic anions enter the cell across the basolateral membrane in exchange for alpha-ketoglutarate (alpha-KG), and the alpha-KG is returned to the interior via Na-alpha-KG cotransport. Indirect coupling to Na has been demonstrated in both isolated membranes and intact renal epithelial cells of species ranging from marine crustaceans to mammals. This mechanism was shown to drive not only cellular accumulation but also secretory transepithelial fluxes of organic anions. Luminal exit of secreted organic anions appears to be carrier mediated but is, at present, poorly understood, with mediated potential-driven efflux and anion exchange-driven efflux implicated in some species. As for organic anions, the renal clearnce of some organic cations approaches the renal plasma flow. Although there is considerable variation in the handling of specific substrates between species, the basic properties of organic cation transport include carrier-mediated potential-driven uptake at the basolateral membrane, intracellular sequestration that reduces the free concentration of the cation, and luminal exit by organic cation-proton exchange. Reabsorptive transport is also observed for some organic cations, but its mechanisms and driving forces are not well understood. C1 NIEHS, CELLULAR & MOLEC PHARMACOL LAB, INTRACELLULAR REGULAT SECT, RES TRIANGLE PK, NC 27709 USA. DUKE UNIV, MARINE LAB, BEAUFORT, NC 28516 USA. MT DESERT ISL BIOL LAB, SALSBURY COVE, ME 04672 USA. RP PRITCHARD, JB (reprint author), NIEHS, CELLULAR & MOLEC PHARMACOL LAB, COMPARAT MEMBRANE PHARMACOL SECT, RES TRIANGLE PK, NC 27709 USA. NR 99 TC 79 Z9 79 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD DEC PY 1991 VL 261 IS 6 BP R1329 EP R1340 PN 2 PG 12 WC Physiology SC Physiology GA GX687 UT WOS:A1991GX68700059 ER PT J AU ZATZ, M WANG, HM AF ZATZ, M WANG, HM TI LOW SALT MIMICS EFFECTS OF DARK PULSES ON CIRCADIAN PACEMAKER IN CULTURED CHICK PINEAL CELLS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE MELATONIN; CELL VOLUME; CIRCADIAN RHYTHMS ID N-ACETYLTRANSFERASE ACTIVITY; PHOTOENDOCRINE TRANSDUCTION; MELATONIN RHYTHM; SODIUM-PUMP; LIGHT; POTASSIUM; INVITRO; OUABAIN; VOLUME; GLAND AB Chick pineal cells in static culture display a persistent photosensitive circadian rhythm of melatonin production and release. Pulses of white light or darkness, in otherwise constant red light, induce phase shifts in subsequent cycles whose magnitude and direction depend on the pahse at which the pulse is given. Such "phase-dependent phase shifts" are mediated by effects on the underlying pacemaker. We reported previously that inhibiting the Na-K-ATP-ase with ouabain or salt solutions lacking potassium evokes phase shifts with the same phase dependence as those induced by pulses of darkness. One of the consequences of inhibiting the sodium pump is cell swelling. To test the relevance of this effect, we exposed chick pineal cells to pulses of medium containing reduced concentrations of NaCl, which should cause cell swelling. These hypotonic solutions induced phase shifts in the melatonin rhythm with the same phase dependence as those caused by pulses of ouabain or darkness. The size of the phase shifts varied with degree of dilution, and phase shifting was prevented by replacement of NaCl. In view of previous results showing that hypertonic media mimicked the phase-shifting effects of light, these results suggest that cell swelling may mediate the darklike effects of ouabain on the circadian pacemaker in chick pineal cells. RP ZATZ, M (reprint author), NIMH, CELL BIOL LAB,BIOCHEM PHARMACOL SECT,BLDG 36, RM 2A-17, LCB, BETHESDA, MD 20892 USA. NR 29 TC 11 Z9 11 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD DEC PY 1991 VL 261 IS 6 BP R1424 EP R1430 PN 2 PG 7 WC Physiology SC Physiology GA GX687 UT WOS:A1991GX68700072 ER PT J AU YONEY, TH PIGOTT, TA LHEUREUX, F ROSENTHAL, NE AF YONEY, TH PIGOTT, TA LHEUREUX, F ROSENTHAL, NE TI SEASONAL-VARIATION IN OBSESSIVE-COMPULSIVE DISORDER - PRELIMINARY EXPERIENCE WITH LIGHT TREATMENT SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article AB The authors surveyed 34 patients with obsessive-compulsive disorder for a history of seasonal variations in symptoms and behavior and treated six of these patients with bright light. Overall, the patients with obsessive-compulsive disorder did not report a greater degree of seasonal variations than normal and no response was seen to bright light therapy in the small number of patients treated. C1 NIMH,CLIN PSYCHOBIOL BRANCH,OUTPATIENT STUDIES UNIT,BLDG 10-4S-239,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NR 12 TC 16 Z9 16 U1 0 U2 0 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 DEC PY 1991 VL 148 IS 12 BP 1727 EP 1729 PG 3 WC Psychiatry SC Psychiatry GA GR842 UT WOS:A1991GR84200016 PM 1957938 ER PT J AU BONNER, JC OSORNIOVARGAS, AR BADGETT, A BRODY, AR AF BONNER, JC OSORNIOVARGAS, AR BADGETT, A BRODY, AR TI DIFFERENTIAL PROLIFERATION OF RAT LUNG FIBROBLASTS INDUCED BY THE PLATELET-DERIVED GROWTH FACTOR-AA, FACTOR-AB, AND FACTOR-BB ISOFORMS SECRETED BY RAT ALVEOLAR MACROPHAGES SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID SMOOTH-MUSCLE CELLS; IDIOPATHIC PULMONARY FIBROSIS; GENE-EXPRESSION; FACTOR PDGF; SIS GENE; C-SIS; RECEPTOR; ASBESTOS; PROTEIN; ALPHA-2-MACROGLOBULIN AB Platelet-derived growth factor (PDGF)-like molecules secreted by alveolar macrophages have been postulated to be mediators of lung fibrogenesis since these cytokines stimulate the proliferation and chemotaxis of lung fibroblasts. We are studying the biology and biochemistry of rat macrophage-derived PDGF and have identified for the first time the specific isoforms of PDGF (-AA, -AB, and -BB) that these macrophages secreted in vitro following activation with either chrysotile asbestos or carbonyl iron spheres. Subsequently, the proliferative response of rat lung fibroblasts (RLF) to the different PDGF isoforms was established. Using several antibodies raised against the distinct isoforms, we established that two different PDGF-like factors with molecular masses of 30 to 34 kD and 16 to 18 kD were contained in alveolar macrophage-conditioned medium. Within each of these molecular mass regions was a mixture of all three PDGF isoforms. We estimated that the 30- to 34-kD PDGF was mainly PDGF-BB (approximately 50%), while the remaining consisted of PDGF-AA (approximately 13%) and PDGF-AB (approximately 37%). Purified recombinant PDGF isoforms were tested for their ability to stimulate the growth of early-passage RLF and Swiss 3T3 cells in a 3-day cell proliferation assay. PDGF-BB and PDGF-AB were the most potent inducers of RLF proliferation and stimulated growth half-maximally at approximately 1 ng/ml and approximately 7 ng/ml, respectively. While these two B-chain-containing dimers stimulated lung fibroblast growth by as much as 150% above control medium, the PDGF-AA homodimer stimulated lung fibroblast proliferation less than 25% above control medium at the highest concentrations tested (20 ng/ml). In contrast, Swiss 3T3 cells proliferated in the presence of all PDGF isoforms, with half-maximal stimulation values between 1 and 3 ng/ml PDGF. Alveolar macrophage-conditioned medium fractionated by gel filtration chromatography in 1 M acetic acid contained two peaks of growth-stimulatory activity for RLF with apparent molecular masses of 30 to 34 kD and 16 to 18 kD. Both of these PDGF-like factors competed for specific [I-125]PDGF-BB binding to RLF. The growth-promoting activity of these two PDGF-like factors was inhibited 60 to 80% by anti-PDGF-BB/AB. These data demonstrate that macrophages produce the three PDGF isoforms and underscore the need to identify the specific isoforms of PDGF in order to understand the biology of a paracrine link that may be operative between the macrophage as an effector cell and the fibroblast target. C1 NIEHS,PULM PATHOBIOL,POB 12233D202,RES TRIANGLE PK,NC 27709. RP BRODY, AR (reprint author), NIEHS,PULM PATHOBIOL,POB 12233D202,RES TRIANGLE PK,NC 27709, USA. RI Osornio Vargas, Alvaro/D-4012-2009; Osornio Vargas, Alvaro/B-4645-2010 OI Osornio Vargas, Alvaro/0000-0001-8287-7102 NR 40 TC 96 Z9 96 U1 1 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 DEC PY 1991 VL 5 IS 6 BP 539 EP 547 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA GV119 UT WOS:A1991GV11900007 PM 1958381 ER PT J AU FLETCHER, JM FRANCIS, DJ PEQUEGNAT, W RAUDENBUSH, SW BORNSTEIN, MH SCHMITT, F BROUWERS, P STOVER, E AF FLETCHER, JM FRANCIS, DJ PEQUEGNAT, W RAUDENBUSH, SW BORNSTEIN, MH SCHMITT, F BROUWERS, P STOVER, E TI NEUROBEHAVIORAL OUTCOMES IN DISEASES OF CHILDHOOD - INDIVIDUAL CHANGE MODELS FOR PEDIATRIC HUMAN IMMUNODEFICIENCY VIRUSES SO AMERICAN PSYCHOLOGIST LA English DT Article ID INFECTION; GROWTH; AIDS C1 NIMH,OFF AIDS PROGRAMS,5600 FISHERS LANE,ROCKVILLE,MD 20857. UNIV TEXAS,SCH MED,DEPT PEDIAT,HOUSTON,TX 77025. UNIV HOUSTON,HOUSTON,TX 77004. MICHIGAN STATE UNIV,COLL EDUC,E LANSING,MI 48824. NICHHD,CHILD & FAMILY RES SECT,BETHESDA,MD 20892. UNIV KENTUCKY,DEPT NEUROL,LEXINGTON,KY 40506. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. RP PEQUEGNAT, W (reprint author), NIMH,OFF AIDS PROGRAMS,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. OI Francis, David/0000-0003-3944-3274 NR 40 TC 23 Z9 23 U1 2 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD DEC PY 1991 VL 46 IS 12 BP 1267 EP 1277 DI 10.1037/0003-066X.46.12.1267 PG 11 WC Psychology, Multidisciplinary SC Psychology GA GU671 UT WOS:A1991GU67100001 PM 1801614 ER PT J AU GAIL, DB AF GAIL, DB TI HYPERBARIC OXYGENATION THERAPY SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Editorial Material RP GAIL, DB (reprint author), NHLBI,DIV LUNG DIS,WESTWOOD BLDG,ROOM 6A07,5333 WESTBARD AVE,BETHESDA,MD 20892, USA. NR 10 TC 6 Z9 6 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD DEC PY 1991 VL 144 IS 6 BP 1414 EP 1421 PG 8 WC Respiratory System SC Respiratory System GA GU988 UT WOS:A1991GU98800037 ER PT J AU SAKAIRI, M YERGEY, AL AF SAKAIRI, M YERGEY, AL TI ELECTROSPRAY MASS-SPECTROMETRY - VARIATION OF STANDARD-DEVIATION OF EXPERIMENTALLY DETERMINED MOLECULAR-WEIGHTS WITH AVERAGE CHARGE NUMBER SO ANALYTICAL SCIENCES LA English DT Article DE ELECTROSPRAY MASS SPECTROMETRY; MOLECULAR WEIGHT; AVERAGE MASS; PEPTIDE; PROTEIN ID ION-SOURCE; IONIZATION AB The variation of the standard deviation of the molecular weights determined by electrospray with the average charge number of multiply charged ions is investigated for peptides and proteins with molecular weights ranging from 1000 to 20000. This result shows the tendency that the standard deviation of experimentally determined molecular weights increases with the average charge number of multiply charged ions. It is found that the molecular weight determination by electrospray accompanies the error of at least the product of 0.06 and the average charge number in the experiment. C1 NICHHD,BETHESDA,MD 20892. RP SAKAIRI, M (reprint author), HITACHI LTD,CENT RES LAB,KOKUBUNJI,TOKYO 185,JAPAN. NR 9 TC 2 Z9 2 U1 0 U2 1 PU JAPAN SOC ANALYTICAL CHEM PI TOKYO PA 26-2 NISHIGOTANDA 1 CHOME SHINAGAWA-KU, TOKYO 141, JAPAN SN 0910-6340 J9 ANAL SCI JI Anal. Sci. PD DEC PY 1991 VL 7 IS 6 BP 835 EP 837 DI 10.2116/analsci.7.835 PG 3 WC Chemistry, Analytical SC Chemistry GA GW214 UT WOS:A1991GW21400001 ER PT J AU VAITKEVICIUS, PV ESSERWEIN, DM MAYNARD, AK OCONNOR, FC FLEG, JL AF VAITKEVICIUS, PV ESSERWEIN, DM MAYNARD, AK OCONNOR, FC FLEG, JL TI FREQUENCY AND IMPORTANCE OF POSTPRANDIAL BLOOD-PRESSURE REDUCTION IN ELDERLY NURSING-HOME PATIENTS SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE FRAIL ELDERLY; NURSING HOMES; HYPOTENSION; POSTPRANDIAL PERIOD; SYNCOPE ID ORTHOSTATIC HYPOTENSION; HEMODYNAMIC-CHANGES; RESPONSES; INGESTION AB Objective: To determine the frequency and importance of postprandial reductions in systolic blood pressure in debilitated, elderly patients receiving nursing home care. Design: Cohort study. Setting: Community-based, university-affiliated, teaching nursing home. Patients: A total of 113 volunteer nursing-home residents with a mean (+/- SD) age of 78 +/- 9 years; seven residents who refused the test meal served as controls. Intervention: Participants had sequential blood pressure measurements for 90 minutes after the administration of a standardized meal. Measurements and Main Results: Of 113 patients, 109 (96%) showed a postprandial reduction in systolic blood pressure (mean reduction, 17.9 +/- 15.5 mm Hg) within 75 minutes; 41 patients (36%) had a reduction in systolic blood pressure of more than 20 mm Hg. Twelve patients (11%) had a reduction in systolic blood pressure to less than 100 mm Hg (mean systolic blood pressure, 88 +/- 6.4 mm Hg); two of these patients became acutely symptomatic. Multiple regression analysis showed that higher premeal systolic blood pressure, a history of syncope, treatment with vasodilators, and dependent posture of the lower extremities during the postprandial period were all associated with a more severe postprandial decline in systolic blood pressure. Systolic blood pressure in noneating control subjects did not change during the same observation period. No significant differences in the mean systolic blood pressure nadir were found between the 14 patients who died during the follow-up period (mean follow-up, 6.1 +/- 3.8 months) and those who survived. Conclusion: Postprandial reductions in systolic blood pressure among elderly nursing-home patients are common, often large, and potentially symptomatic, but they do not generally presage subsequent intermediate-term mortality. C1 NIA,FRANCIS SCOTT KEY MED CTR,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DIV GERIATR MED,BALTIMORE,MD 21205. FRANCIS SCOTT KEY MED CTR,BALTIMORE,MD. FU NIA NIH HHS [5T32AG00120-03] NR 20 TC 80 Z9 81 U1 0 U2 6 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 DEC 1 PY 1991 VL 115 IS 11 BP 865 EP 870 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA GR171 UT WOS:A1991GR17100005 PM 1952473 ER PT J AU STEWART, GR OLNEY, JW PATHIKONDA, M SNIDER, WD AF STEWART, GR OLNEY, JW PATHIKONDA, M SNIDER, WD TI EXCITOTOXICITY IN THE EMBRYONIC CHICK SPINAL-CORD SO ANNALS OF NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; METHYL-D-ASPARTATE; ABNORMAL GLUTAMATE METABOLISM; EXCITATORY AMINO-ACIDS; KAINIC ACID; DOMOIC ACID; MOTOR-NEURON; PARKINSONISM-DEMENTIA; NERVOUS-SYSTEM; BINDING-SITES AB Recent evidence implicates excitatory amino acids (EAAs), acting as excitotoxic agents, in the pathogenesis of neurological disorders involving the spinal cord. In this study, we used the chick embryo spinal cord as an in vitro model for studying the sensitivity of spinal neurons to the excitotoxic effects of EAA agonists. Compounds tested include the prototypic receptor-specific agonists, N-methyl-D-aspartate (NMDA), quisqualic acid (Quis), and kainic acid (KA), and the plant-derived excitotoxic food poisons, beta-N-oxalylamino-L-alanine, beta-N-methylamino-L-alanine, and domoic acid. Each agonist induced concentration-dependent acute degeneration of neurons distributed throughout the spinal cord. These cytopathological changes consisted of acute edematous degeneration of dendrosomal structures in the dorsal horn and intermediate zone, and dark cell changes with intracytoplasmic vacuolization of motor neurons; this damage is identical to that induced by excitotoxin agonists in other regions of the central nervous system. The NMDA receptor-specific antagonist MK-801 completely blocked toxicity of NMDA, and the nonNMDA antagonist CNQX preferentially blocked the toxicity of Quis- and KA-type agonists in the spinal cord. Our findings suggest that (1) the majority of spinal neurons have all three subtypes of EAA receptors, making them acutely vulnerable to excitotoxin exposure; and (2) EAA antagonists are effective in preventing excitotoxin-induced damage of the spinal cord. C1 WASHINGTON UNIV,SCH MED,DEPT PSYCHIAT,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT NEUROL,ST LOUIS,MO 63110. RP STEWART, GR (reprint author), NIMH,CTR ANIM,NEUROPHYSIOL LAB,POB 289,POOLESVILLE,MD 20837, USA. FU NIA NIH HHS [AG 05681]; NIEHS NIH HHS [T32 ES 07066]; NIMH NIH HHS [MH 38894] NR 52 TC 58 Z9 58 U1 0 U2 2 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 1991 VL 30 IS 6 BP 758 EP 766 DI 10.1002/ana.410300604 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA GT705 UT WOS:A1991GT70500003 PM 1686386 ER PT J AU KORN, EL GRAUBARD, BI AF KORN, EL GRAUBARD, BI TI A NOTE ON THE LARGE SAMPLE PROPERTIES OF LINEARIZATION, JACKKNIFE AND BALANCED REPEATED REPLICATION METHODS FOR STRATIFIED SAMPLES SO ANNALS OF STATISTICS LA English DT Note DE STRATIFIED SAMPLING; LINEARIZATION METHOD; JACKKNIFE METHOD; BALANCED REPEATED REPLICATION; HYPOTHESIS TESTING ID STATISTICS; INFERENCE AB Krewski and Rao consider inference for a (nonlinear) function of a vector of finite population means 0 = g(YBAR). For a sequence of finite populations with increasing number of strata, they demonstrate that theta = g(yBAR) is asymptotically normal, where yBAR is the usual unbiased stratified estimator of YBAR. Additionally, they demonstrate that (theta - theta)/upsilon1/2(theta) is asymptotically a standard normal distribution, where upsilon(theta) is a variance estimator obtained using linearization, jackknife or balanced repeated replication (BRR) methods. In this note we extend their results to when the partial first derivatives (g1(mu), g2(mu),..., g(p)(mu)) = 0, where mu is the limit of YBAR with increasing number of strata. We explore the asymptotic distribution of (theta - theta)/upsilon1/2(theta) and show (1) that it is no longer normal and (2) that it depends upon which variance estimator is used. We describe an application of these results to hypothesis testing using complex survey data. C1 NCI,BIOMETRY BRANCH,BETHESDA,MD 20892. RP KORN, EL (reprint author), NCI,BIOMETR RES BRANCH,BETHESDA,MD 20892, USA. NR 11 TC 2 Z9 2 U1 1 U2 1 PU INST MATHEMATICAL STATISTICS PI HAYWARD PA IMS BUSINESS OFFICE-SUITE 6 3401 INVESTMENT BLVD, HAYWARD, CA 94545 SN 0090-5364 J9 ANN STAT JI Ann. Stat. PD DEC PY 1991 VL 19 IS 4 BP 2275 EP 2279 DI 10.1214/aos/1176348400 PG 5 WC Statistics & Probability SC Mathematics GA GZ661 UT WOS:A1991GZ66100034 ER PT J AU PANDEY, RN WILSON, JD ZHAO, XG SCHLOM, J AF PANDEY, RN WILSON, JD ZHAO, XG SCHLOM, J TI PHOTOLABELING - A NEW APPROACH FOR RADIOIODINATION SO ANTIBODY IMMUNOCONJUGATES AND RADIOPHARMACEUTICALS LA English DT Article; Proceedings Paper CT 3RD CONF ON RADIOIMMUNODETECTION AND RADIOIMMUNOTHERAPY OF CANCER CY NOV 14-17, 1990 CL PRINCETON, NJ SP CTR MOLEC MED & IMMUNOL, JOHNS HOPKINS ONCOL CTR, AMER COLL RADIOL, BRISTOL MYERS SQUIBB, BURROUGHS WELLCOME, DOW CHEM, IMMUNOMEDICS, ROBERT WOOD JOHNSON PHARM RES INST, ORGANON TEKNIKA, SORIN BIOMEDICA ID MONOCLONAL-ANTIBODY B72.3 AB Photolabeling has been used in the past for studying the active sites of enzymes and antibodies. The nonspecific nature of photolabeling can be used for the preparation of hapten-carrier conjugates for antibody generation against the hapten. Here the concept of photolabeling has been extended to the radioiodination of monoclonal antibodies. This was achieved by first radioiodinating 4-azido-2-hydroxybenzoic acid commonly known as p-azidosalicylic acid (PAZSA) using the IODO-GEN method. Radioiodinated PAZSA was then mixed with monoclonal antibody B72.3 and photolysed with UV light for 40 minutes. The biodistribution of MoAb B72.3 iodinated by photolabeling (I-125PAZSA-B72.3) and by the IODO-GEN method (I-131-B72.3) were compared in female athymic nude mice bearing LS-174T human colon carcinoma xenografts. Both preparations were mixed and given in a single tail vein injection. The animals were sacrificed 6 days later. Various organs were removed and their radioactivities determined. The data indicated that dehalogenation of the photoradioiodinated antibody was less extensive than that of the antibody iodinated by the conventional IODO-GEN method. The photocoupling procedure for radioiodination is similar to other indirect methods except that it does not require the presence of a lysine residue on the macromolecule, a prerequisite for most indirect methods. C1 NCI,DIV CANC BIOL & DIAG,BETHESDA,MD 20892. RP PANDEY, RN (reprint author), VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT RADIOL,DIV RADIAT PHYS,RICHMOND,VA 23298, USA. NR 10 TC 4 Z9 4 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0892-7049 J9 ANTIBODY IMMUNOCONJ JI Antib. Immunoconjug. Radiopharm. PD WIN PY 1991 VL 4 IS 4 BP 399 EP 407 PG 9 WC Immunology; Radiology, Nuclear Medicine & Medical Imaging SC Immunology; Radiology, Nuclear Medicine & Medical Imaging GA HT510 UT WOS:A1991HT51000003 ER PT J AU GANSOW, OA BRECHBIEL, MW PIPPIN, CG MCMURRY, TJ LAMBRECHT, R COLCHER, D SCHLOM, J ROSELLI, M STRAND, M HUNEKE, RB RUEGG, CL AF GANSOW, OA BRECHBIEL, MW PIPPIN, CG MCMURRY, TJ LAMBRECHT, R COLCHER, D SCHLOM, J ROSELLI, M STRAND, M HUNEKE, RB RUEGG, CL TI LEAD AND BISMUTH COMPLEXES OF FUNCTIONALIZED DTPA LIGANDS AND OF THE POLYAZACYCLOALKANE-N-ACETIC ACID DOTA - UTILITY FOR RADIOIMMUNOIMAGING AND RADIOIMMUNOTHERAPY SO ANTIBODY IMMUNOCONJUGATES AND RADIOPHARMACEUTICALS LA English DT Article; Proceedings Paper CT 3RD CONF ON RADIOIMMUNODETECTION AND RADIOIMMUNOTHERAPY OF CANCER CY NOV 14-17, 1990 CL PRINCETON, NJ SP CTR MOLEC MED & IMMUNOL, JOHNS HOPKINS ONCOL CTR, AMER COLL RADIOL, BRISTOL MYERS SQUIBB, BURROUGHS WELLCOME, DOW CHEM, IMMUNOMEDICS, ROBERT WOOD JOHNSON PHARM RES INST, ORGANON TEKNIKA, SORIN BIOMEDICA ID COLON CARCINOMA XENOGRAFTS; TAC MONOCLONAL-ANTIBODY; GENERATOR; BI-212; MICE; MELANOMA; IN-111; PB-212 AB Several chemically functionalized derivatives of diehtylenetriaminepentaacetic acid (DTPA), were evaluated for use in linking radioactive Lead(II) and Bismuth(III) to monoclonal antibodies (mAb). Lack of success in achieving in vivo stability prompted preparation of macrocyclic ligands. To prepare a functionalized derivative of DOTA (1,4,7,10-tetraazacyclododecane-N, N',N'',N'''-tetraacetic acid), a novel synthesis was devised. Thereby, the di-Boc-N,N'-ethylenediaminediacetic acid di-N-hydroxy-succinimide ester was reacted with 2-p-NO2-Bz-ethylenediamine and the resultant diamide reduced to form the substituted cyclen which when alkylated produced the desired bifunctional DOTA. Each of these ligands was conjugated with the monoclonal antibody (mAb) 103A, which is specific for gp70 expressed on Rauscher virus-infected cells. These conjugates showed no loss of immunoreactivity in vivo as assessed by radioiodination. The in vivo stability of the Bi-206-chelate-103A conjugates was compared to S-35 metabolically labeled mAb 103A in normal and in Rauscher virus-infected leukemic mice. Rapid decrease of Bi-206 levels in blood and high uptake in kidney for the DTPA modified ligands studied as compared to the S-35 levels in normal animals indicated that the DTPA derivatives listed above were unstable. In contrast, comparable blood levels of Bi-206 and S-35 were observed in blood and kidney in normal animals for the DOTA linked mAb. Furthermore, in tumor bearing mice, high tumor accretions of Bi-206 were seen only for DOTA-103A. The in vivo stabilities of Pb-203 DOTA and of Bi-206- (2-p-SCN-Bz-trans-cyclohexylDTPA), a new DTPA derivative, were also examined by use of their conjugates with mAb B72.3 in the LS-174T tumor model. Tissue distributions studies demonstrated the stability of the Pb-203 and Bi-206 conjugates. The utility of the Pb-203 derivative for scintigraphy was shown by a gamma camera imaging study. C1 KING FAISAL SPECIALIST HOSP & RES CTR,RIYADH 11211,SAUDI ARABIA. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. RP GANSOW, OA (reprint author), NCI,RADIAT ONCOL BRANCH,CHEM SECT,BLDG 10,ROOM B3-B69,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 34 TC 16 Z9 16 U1 1 U2 6 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0892-7049 J9 ANTIBODY IMMUNOCONJ JI Antib. Immunoconjug. Radiopharm. PD WIN PY 1991 VL 4 IS 4 BP 413 EP 425 PG 13 WC Immunology; Radiology, Nuclear Medicine & Medical Imaging SC Immunology; Radiology, Nuclear Medicine & Medical Imaging GA HT510 UT WOS:A1991HT51000005 ER PT J AU YORKE, ED WESSELS, BW BRADLEY, EW AF YORKE, ED WESSELS, BW BRADLEY, EW TI ABSORBED DOSE AVERAGES AND DOSE HETEROGENEITIES IN RADIOIMMUNOTHERAPY SO ANTIBODY IMMUNOCONJUGATES AND RADIOPHARMACEUTICALS LA English DT Article ID SYSTEM AB Radioimmunotherapy (RIT) using beta emitters can produce very heterogeneous activity and absorbed dose distributions. To characterize these, we theoretically compared three measures of absorbed dose. The equilibrium dose is the absorbed dose to an infinite medium delivered by the average cumulated activity. The volume average dose is a simple average of the absorbed dose over the volume of interest. When only a small fraction of the activity is near the edge of the tumor, the equilibrium dose is a good estimate of the volume average dose. The survival average dose is the spatially uniform absorbed dose producing the same surviving cell fraction as the heterogeneous absorbed dose distribution being evaluated. A linear-quadratic model is used together with simple absorbed dose distributions to show that the absorbed dose distribution strongly affects the surviving fraction of cells. For therapeutically significant volume average absorbed doses and realistic radiobiological parameters, the surviving fraction of cells is determined more by lower absorbed dose regions than by the volume average absorbed dose. C1 NIH, SPECIAL REVIEW SECT, BETHESDA, MD 20892 USA. RP YORKE, ED (reprint author), GEORGETOWN UNIV, MED CTR, DIV RADIAT ONCOL & BIOPHYS, 901 23RD ST NW, WASHINGTON, DC 20007 USA. NR 18 TC 10 Z9 10 U1 1 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7049 J9 ANTIBODY IMMUNOCONJ JI Antib. Immunoconjug. Radiopharm. PD WIN PY 1991 VL 4 IS 4 BP 623 EP 629 PG 7 WC Immunology; Radiology, Nuclear Medicine & Medical Imaging SC Immunology; Radiology, Nuclear Medicine & Medical Imaging GA HT510 UT WOS:A1991HT51000030 ER PT J AU SCHLOM, J AF SCHLOM, J TI NEW APPROACHES TO IMPROVED ANTIBODY TARGETING SO ANTIBODY IMMUNOCONJUGATES AND RADIOPHARMACEUTICALS LA English DT Article; Proceedings Paper CT 3RD CONF ON RADIOIMMUNODETECTION AND RADIOIMMUNOTHERAPY OF CANCER CY NOV 14-17, 1990 CL PRINCETON, NJ SP CTR MOLEC MED & IMMUNOL, JOHNS HOPKINS ONCOL CTR, AMER COLL RADIOL, BRISTOL MYERS SQUIBB, BURROUGHS WELLCOME, DOW CHEM, IMMUNOMEDICS, ROBERT WOOD JOHNSON PHARM RES INST, ORGANON TEKNIKA, SORIN BIOMEDICA ID TUMOR-ASSOCIATED ANTIGENS; MONOCLONAL-ANTIBODY; ATHYMIC MICE; HUMAN-BREAST; RECOMBINANT; INTERFERON; CELLS; EXPRESSION; INVIVO; RADIOIMMUNOTHERAPY RP SCHLOM, J (reprint author), NIH,TUMOR IMMUNOL & BIOL LAB,BLDG 10,ROOM 8B07,BETHESDA,MD 20892, USA. NR 27 TC 5 Z9 5 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0892-7049 J9 ANTIBODY IMMUNOCONJ JI Antib. Immunoconjug. Radiopharm. PD WIN PY 1991 VL 4 IS 4 BP 819 EP 828 PG 10 WC Immunology; Radiology, Nuclear Medicine & Medical Imaging SC Immunology; Radiology, Nuclear Medicine & Medical Imaging GA HT510 UT WOS:A1991HT51000053 ER PT J AU PAPOUSEK, M HWANG, SFC AF PAPOUSEK, M HWANG, SFC TI TONE AND INTONATION IN MANDARINE BABYTALK TO PRESYLLABIC INFANTS - COMPARISON WITH REGISTERS OF ADULT CONVERSATION AND FOREIGN-LANGUAGE INSTRUCTION SO APPLIED PSYCHOLINGUISTICS LA English DT Article ID MATERNAL SPEECH; MOTHERS SPEECH; CONTOURS; FEATURES; CHILDREN AB Six native speakers of Mandarin Chinese recorded 140 preselected utterances in three role-play contexts that differentially elicited registers of babytalk to presyllabic infants (BTP), foreign language instruction (FLI), and adult conversation (AC). Sound spectrograms were used to obtain 10 measures of fundamental frequency (Fo) patterns for comparisons among the three registers. In FLI, the speakers expanded Fo patterns in time and Fo range in comparison with AC. They clarified lexical tonal information and seemed to reduce suprasegmental information. In BTP, the speakers raised peak and minimum Fo, reduced the rate of Fo fluctuations, and increased the proportion of terminal rising contours. The speakers reduced, neglected, or modified lexical tonal information in favor of simplified and clarified intonation contours. The significance of the results is discussed in relation to tone acquisition in children and to a universal intuitive didactic competence in caretakers. C1 MAX PLANCK INST PSYCHIAT,W-8000 MUNICH 40,GERMANY. NICHHD,BETHESDA,MD. NR 44 TC 38 Z9 38 U1 3 U2 9 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0142-7164 J9 APPL PSYCHOLINGUIST JI Appl. Psycholinguist. PD DEC PY 1991 VL 12 IS 4 BP 481 EP 504 DI 10.1017/S0142716400005889 PG 24 WC Linguistics; Psychology, Experimental SC Linguistics; Psychology GA HG908 UT WOS:A1991HG90800005 ER PT J AU BERNSTEIN, EF FRIAUF, WS SMITH, PD COLE, JW SOLOMON, RE FESSLER, JF THOMAS, GF BLACK, C RUSSO, A AF BERNSTEIN, EF FRIAUF, WS SMITH, PD COLE, JW SOLOMON, RE FESSLER, JF THOMAS, GF BLACK, C RUSSO, A TI TRANSCUTANEOUS DETERMINATION OF TISSUE DIHEMATOPORPHYRIN ETHER CONTENT - A DEVICE TO OPTIMIZE PHOTODYNAMIC THERAPY SO ARCHIVES OF DERMATOLOGY LA English DT Article ID OXYGEN DEPENDENCE; FLAP SURVIVAL; HEMATOPORPHYRIN; PHOTOSENSITIZERS; PHOTOTHERAPY; PREDICTION; TUMORS; CELLS; SKIN AB Photodynamic therapy involves the use of light of appropriate wavelength to excite a photosensitizer resulting in tissue destruction. The photosensitizer dihematoporphyrin ether is selectively retained in tumors allowing for tumor destruction while sparing normal structures. Accessibility of skin tumors makes them well suited for photodynamic therapy. Tissue and tumor dihematoporphyrin ether content is estimated based on the amount of dihematoporphyrin ether administered. In our study, skin dihematoporphyrin ether content was measured in guinea pigs transcutaneously by a hand-held fluorometer and compared with dihematoporphyrin ether determinations done on skin biopsy specimens. Fluorometry was performed on guinea pigs receiving 0, 2.5, 5, 10, and 25 mg/kg of dihematoporphyrin ether. Transcutaneous measurements of skin fluorescence increased with increasing dihematoporphyrin ether dose and correlated well with skin dihematoporphyrin ether content as determined by extracting dihematoporphyrin other from skin samples. Transcutaneous fluorescent measurements of guinea pigs given 0 and 2.5, 2.5 and 5,5 and 10, and 10 and 25 mg/kg of dihematoporphyrin ether differed in a statistically significant manner. Transcutaneous fluorometric determination of dihematoporphyrin ether content and extraction of dihematoporphyrin ether from skin samples were able to reflect differences in dihematoporphyrin ether dosing and presumably skin dihematoporphyrin ether content. However, transcutaneous fluorometry provides an instantaneous estimate of tissue dihematoporphyrin ether without the need for a tissue sample. This may provide a clinical tool to predict more accurately the optimal light dose necessary to maximize photodynamic therapy. C1 NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NIH,DIV BIOENGN,BETHESDA,MD 20892. RP BERNSTEIN, EF (reprint author), HAHNEMANN UNIV,SCH MED,DIV DERMATOL MS401,PHILADELPHIA,PA 19102, USA. NR 22 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD DEC PY 1991 VL 127 IS 12 BP 1794 EP 1798 DI 10.1001/archderm.127.12.1794 PG 5 WC Dermatology SC Dermatology GA HB975 UT WOS:A1991HB97500004 PM 1845278 ER PT J AU GROSS, EG PECK, GL DIGIOVANNA, JJ AF GROSS, EG PECK, GL DIGIOVANNA, JJ TI ADVERSE REACTION TO FENRETINIDE, A SYNTHETIC RETINOID SO ARCHIVES OF DERMATOLOGY LA English DT Letter C1 UNIV MARYLAND,SCH MED,DEPT DERMATOL,BALTIMORE,MD 21201. NCI,DERMATOL BRANCH,BETHESDA,MD 20892. RP GROSS, EG (reprint author), UNIV CONNECTICUT,VET ADM HOSP,MED CTR,NEWINGTON,CT 06111, USA. NR 8 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD DEC PY 1991 VL 127 IS 12 BP 1849 EP 1850 DI 10.1001/archderm.127.12.1849 PG 2 WC Dermatology SC Dermatology GA HB975 UT WOS:A1991HB97500022 PM 1845290 ER PT J AU MOLCHAN, SE VITIELLO, B MINICHIELLO, M SUNDERLAND, T AF MOLCHAN, SE VITIELLO, B MINICHIELLO, M SUNDERLAND, T TI RECIPROCAL CHANGES IN PSYCHOSIS AND MOOD AFTER PHYSOSTIGMINE IN A PATIENT WITH ALZHEIMERS-DISEASE SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Letter RP MOLCHAN, SE (reprint author), NIMH,CTR CLIN,9000 ROCKVILLE PIKE,BLDG 10,RM 3D-41,BETHESDA,MD 20892, USA. NR 4 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD DEC PY 1991 VL 48 IS 12 BP 1113 EP 1114 PG 2 WC Psychiatry SC Psychiatry GA GW653 UT WOS:A1991GW65300010 PM 1845230 ER PT J AU KLIPPEL, JH AF KLIPPEL, JH TI RAYNAUDS-PHENOMENON - THE FRENCH TRICOLOR SO ARCHIVES OF INTERNAL MEDICINE LA English DT Review ID CONNECTIVE-TISSUE DISEASE; SYSTEMIC-SCLEROSIS; VASOCONSTRICTOR REFLEX; DOUBLE-BLIND; BLOOD-FLOW; SCLERODERMA; EVOLUTION; HAND AB Recent epidemiologic surveys indicate that episodic vasospasm of arterioles (Raynaud's phenomenon) is a common finding in the general population. In a small minority of these individuals, an underlying, often reversible cause or systemic disease associated with vasospasm can be identified. The range of these so-called secondary forms of vasospasm is broad and includes systemic rheumatic syndromes, vibration-induced vascular injury, drug-induced vasospasm, and infectious disorders. Several different physiologic mechanisms may be responsible for vasospasm; hyperactivity of the sympathetic nervous system and abnormal adrenergic receptor function appear to be most important. RP KLIPPEL, JH (reprint author), NIAMSD,ARTHRITIS & RHEUMATISM BRANCH,BLDG 10,ROOM 9N228,BETHESDA,MD 20892, USA. NR 34 TC 15 Z9 15 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD DEC PY 1991 VL 151 IS 12 BP 2389 EP 2393 DI 10.1001/archinte.151.12.2389 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA HF433 UT WOS:A1991HF43300006 PM 1746995 ER PT J AU GREWAL, RP DOPPELT, SH THOMPSON, MA KATZ, D BRADY, RO BARTON, NW AF GREWAL, RP DOPPELT, SH THOMPSON, MA KATZ, D BRADY, RO BARTON, NW TI NEUROLOGIC COMPLICATIONS OF NONNEURONOPATHIC GAUCHERS-DISEASE SO ARCHIVES OF NEUROLOGY LA English DT Article ID SPINAL-CORD COMPRESSION AB We describe eight patients with type 1 Gaucher's disease who developed neurologic complications that were secondary to systemic features of the illness. Four patients experienced neurologic difficulties because of coagulopathy, and the other four patients had involvement of the nervous system secondary to skeletal disease. Early recognition of these complications in patients with type 1 Gaucher's disease may lead to improved neurologic outcome. C1 NINCDS,OFF CLIN DIRECTOR,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,DEPT ORTHOPED SURG,BOSTON,MA 02114. RP GREWAL, RP (reprint author), NINCDS,DEV & METAB NEUROL BRANCH,BLDG 10,ROOM 3D03,BETHESDA,MD 20892, USA. NR 8 TC 21 Z9 21 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD DEC PY 1991 VL 48 IS 12 BP 1271 EP 1272 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA GZ420 UT WOS:A1991GZ42000020 PM 1845033 ER PT J AU HALL, WH AF HALL, WH TI CLINICAL USE OF BOTULINUM TOXIN - NATIONAL-INSTITUTES-OF-HEALTH CONSENSUS DEVELOPMENT CONFERENCE STATEMENT, NOVEMBER 12-14, 1990 SO ARCHIVES OF NEUROLOGY LA English DT Editorial Material RP HALL, WH (reprint author), NIH,BLDG 1,ROOM 260,BETHESDA,MD 20892, USA. NR 0 TC 49 Z9 49 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD DEC PY 1991 VL 48 IS 12 BP 1294 EP 1298 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA GZ420 UT WOS:A1991GZ42000025 ER PT J AU TAUBENBERGER, JK JAFFE, ES MEDEIROS, LJ AF TAUBENBERGER, JK JAFFE, ES MEDEIROS, LJ TI THYMOMA WITH ABUNDANT L26-POSITIVE ASTEROID CELLS - A CASE-REPORT WITH AN ANALYSIS OF NORMAL THYMUS AND THYMOMA SPECIMENS SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Note ID PARAFFIN-EMBEDDED TISSUE; B-CELLS; LYMPHOMA AB A case of thymoma is presented that was referred for consultation with the differential diagnosis of thymoma and non-Hodgkin's lymphoma. Immunoperoxidase studies performed on fixed, paraffin-embedded sections demonstrated the presence of numerous epithelial cells, supporting the diagnosis of thymoma. However, the pan-B-cell antibody L26 also demonstrated abundant staining, an unexpected finding that may be a potential source of diagnostic confusion. The L26 antibody stained cells with elongate cell processes that interdigitated between and surrounded thymocytes. We pursued this observation by performing immunoperoxidase studies on three thymoma and seven normal thymus specimens using fixed sections. Each thymoma had occasional cells or small clusters of L26-positive cells scattered throughout the neoplasm. In sections of normal thymus, L26-positive cells were also found, almost exclusively in the medullary regions. These cells tended to congregate around Hassall's corpuscles and had elongate cell processes that often surrounded medullary lymphocytes. Occasional small lymphocytes also appeared to be positive for L26. Our results demonstrate that cell populations that express B-cell antigens are consistently found in the thymic medulla and that these cells may be numerous in occasional thymomas. The presence of many L26-positive cells in a mediastinal mass should not dissuade one from making the diagnosis of thymoma if all other findings are consistent with that interpretation. C1 NCI,PATHOL LAB,HEMATOPATHOL SECT,BLDG 10,ROOM 2N108,BETHESDA,MD 20892. NR 12 TC 4 Z9 4 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD DEC PY 1991 VL 115 IS 12 BP 1254 EP 1257 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA GZ342 UT WOS:A1991GZ34200015 PM 1768216 ER PT J AU STOTTER, H LOTZE, MT AF STOTTER, H LOTZE, MT TI HUMAN LYMPHOKINE-ACTIVATED KILLER-CELL ACTIVITY - ROLE OF IL-2, IL-4, AND IL-7 SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 44TH ANNUAL CANCER SYMP OF THE SOC OF SURGICAL ONCOLOGY CY MAR 22, 1991 CL ORLANDO, FL SP SOC SURG ONCOL ID CYTO-TOXIC LYMPHOCYTES; DOSE RECOMBINANT INTERLEUKIN-2; HUMAN PERIPHERAL-BLOOD; GROWTH-FACTOR; PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDES; INTERFERON-GAMMA; CYCLOSPORINE-A; T GENERATION; LAK CELLS; PROLIFERATION AB The T-cell growth factors interleukin 2 (IL-2) and interleukin 7 (IL-7) induce lymphokine-activated killer (LAK) cell activity in short-term cultures of human peripheral blood mononuclear cells. Interleukin 4 (IL-4), another T-cell growth factor, induces LAK cell activity in IL-2-prestimulated lymphocytes only and inhibits LAK cell generation in normal peripheral blood mononuclear cells. Our studies of the processes involved using 21-mer phosphorothioate antisense oligonucleotides to the sequence adjacent to the start codon of IL-2 mRNA or IL-4 mRNA (effective concentration, 5 to 10-mu-mol/L) and cyclosporine (0.01 to 1.0-mu-g/mL) or FK506 (0.01 to 1.0 ng/mL) demonstrate that IL-7-induced LAK cell activity is independent of IL-2 production and is regulated by endogenously generated IL-4. Like IL-2, IL-7 stimulated production of tumor necrosis factor alpha, but we failed to detect interferon gamma in IL-7-stimulated cultures. The implication of this regulatory feedback in IL-7-induced LAK cell generation for clinical applications is discussed. C1 UNIV PITTSBURGH,SURG ONCOL SECT,497 SCAIFE HALL,PITTSBURGH,PA 15261. UNIV PITTSBURGH,DEPT SURG,PITTSBURGH,PA 15261. NCI,SURG BRANCH,BETHESDA,MD 20892. NR 54 TC 14 Z9 14 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD DEC PY 1991 VL 126 IS 12 BP 1525 EP 1530 PG 6 WC Surgery SC Surgery GA GZ343 UT WOS:A1991GZ34300016 PM 1726819 ER PT J AU FOLSOM, AR WU, KK DAVIS, CE CONLAN, MG SORLIE, PD SZKLO, M AF FOLSOM, AR WU, KK DAVIS, CE CONLAN, MG SORLIE, PD SZKLO, M TI POPULATION CORRELATES OF PLASMA-FIBRINOGEN AND FACTOR-VII, PUTATIVE CARDIOVASCULAR RISK-FACTORS SO ATHEROSCLEROSIS LA English DT Article DE ARIC STUDY; BLOOD COAGULATION FACTORS; CORONARY DISEASE; FACTOR-VII; FIBRINOGEN ID ISCHEMIC-HEART-DISEASE; MIDDLE-AGED MEN; IMPROVED LIPOLYTIC EFFICIENCY; MYOCARDIAL-INFARCTION; COAGULANT ACTIVITY; ENZYMATIC DETERMINATION; INDUSTRIAL-POPULATION; TRIGLYCERIDE LEVELS; HEMOSTATIC FACTORS; BASELINE DATA AB Recent prospective investigations have reported that higher plasma fibrinogen concentrations and higher factor VII coagulant activity are associated with greater risk of cardiovascular disease. To discover what characteristics may influence fibrinogen and factor VII, we analyzed data from the Atherosclerosis Risk in Communities Study obtained from over 12000 men and women, aged 45-64 years, from four communities in December 1986 to June 1989. Fibrinogen was higher in blacks than whites and in women than men; in general, it increased with age, smoking, body size, diabetes, fasting serum insulin, LDL cholesterol, lipoprotein(a), leukocyte count, and menopause, and it decreased with ethanol intake, physical activity, HDL cholesterol, and female hormone use. Factor VII was higher in women than men and, in women, increased with age; in both sexes, it increased with body size, triglycerides, LDL cholesterol, and HDL cholesterol, and it decreased with ethanol intake. These findings indicate that elevations in fibrinogen and factor VII may be modifiable through appropriate lifestyle changes. C1 UNIV TEXAS,SCH MED,DIV HEMATOL ONCOL,HOUSTON,TX 77030. COLLABORAT STUDIES COORDINATING CTR,CHAPEL HILL,NC 27514. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD 21205. RP FOLSOM, AR (reprint author), UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,1300 S 2ND ST,SUITE 300,MINNEAPOLIS,MN 55454, USA. RI Wu, Kenneth Kun-Yu/B-1070-2010 FU NHLBI NIH HHS [N01-HC-55015, N01-HC-55016, N01-HC-55018] NR 54 TC 340 Z9 344 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD DEC PY 1991 VL 91 IS 3 BP 191 EP 205 DI 10.1016/0021-9150(91)90167-2 PG 15 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA GY234 UT WOS:A1991GY23400003 PM 1789804 ER PT J AU KERNS, RD SOUTHWICK, S GILLER, EL HAYTHORNTHWAITE, JA JACOB, MC ROSENBERG, R AF KERNS, RD SOUTHWICK, S GILLER, EL HAYTHORNTHWAITE, JA JACOB, MC ROSENBERG, R TI THE RELATIONSHIP BETWEEN REPORTS OF PAIN-RELATED SOCIAL INTERACTIONS AND EXPRESSIONS OF PAIN AND AFFECTIVE DISTRESS SO BEHAVIOR THERAPY LA English DT Article ID MEDIATING ROLE; BEHAVIOR; SPOUSE; REINFORCEMENT C1 YALE UNIV,SCH MED,NEW HAVEN,CT 06510. UNIV CONNECTICUT,STORRS,CT 06268. NIA,BETHESDA,MD 20892. RP KERNS, RD (reprint author), VET ADM MED CTR,950 CAMPBELL AVE,W HAVEN,CT 06516, USA. NR 28 TC 38 Z9 38 U1 2 U2 2 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 SN 0005-7894 J9 BEHAV THER JI Behav. Therapy PD WIN PY 1991 VL 22 IS 1 BP 101 EP 111 DI 10.1016/S0005-7894(05)80248-5 PG 11 WC Psychology, Clinical SC Psychology GA EY744 UT WOS:A1991EY74400009 ER PT J AU GRAFMAN, J HENDLER, J AF GRAFMAN, J HENDLER, J TI PLANNING AND THE BRAIN SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Article C1 UNIV MARYLAND, DEPT COMP SCI, COLLEGE PK, MD 20742 USA. RP GRAFMAN, J (reprint author), NINCDS, MED NEUROL BRANCH, COGNIT NEUROSCI SECT, BLDG 10, ROOM 5C422, BETHESDA, MD 20892 USA. NR 13 TC 11 Z9 11 U1 0 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 DEC PY 1991 VL 14 IS 4 BP 563 EP 563 PG 1 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA GX827 UT WOS:A1991GX82700013 ER PT J AU MCCONNELL, FM STEPHENS, LR SHEARS, SB AF MCCONNELL, FM STEPHENS, LR SHEARS, SB TI MULTIPLE ISOMERS OF INOSITOL PENTAKISPHOSPHATE IN EPSTEIN-BARR-VIRUS-TRANSFORMED (T5-1) LYMPHOCYTES-B - IDENTIFICATION OF INOSITOL 1,3,4,5,6-PENTAKISPHOSPHATE, D-INOSITOL 1,2,4,5,6-PENTAKISPHOSPHATE AND L-INOSITOL 1,2,4,5,6-PENTAKISPHOSPHATE SO BIOCHEMICAL JOURNAL LA English DT Article ID ADRENAL GLOMERULOSA CELLS; SURFACE-IMMUNOGLOBULIN; PHOSPHORYLATION; PHOSPHATES; 1,3,4,6-TETRAKISPHOSPHATE; 1,3,4-TRISPHOSPHATE; TETRAKISPHOSPHATE; HEXAKISPHOSPHATE; 5-PHOSPHATASE; PROLIFERATION AB Substantial amounts of three [H-3]InsP5 isomers were detected in [H-3]inositol-labelled human lymphoblastoid (T5-1) cells. Their structures were determined by h.p.l.c. [Phillippy & Bland (1988) Anal. Biochem. 175, 162-166], and by utilizing a stereospeCifiC D-inositol 1,2,4,5,6-pentakisphosphate 3-kinase from Dictyostelium discoideum [Stephens & Irvine (1990) Nature (London) 346, 580-583]. The structures were: inositol 1,3,4,5,6-pentakisphosphate, D-inositol 1,2,4,5,6-pentakisphosphate and L-inositol 1,2,4,5,6-pentakisphosphate. The relative proportions of these isomers (approx. 73:14:14 respectively) were unaffected by cross-linking anti-IgD receptors. The T5-1 cells also contained InsP6 and three Ins P4s, which were identified as the 1,3,4,5, 1,3,4,6 and 3,4,5,6 isomers. In incubations with permeabilized T5-1 cells, both 1,3,4,6 and 3,4,5,6 isomers of InsP4 were phosphorylated solely to Ins(1,3,4,5,6)P5. Permeabilized cells also dephosphorylated InsP6, even in the presence of a large excess of glucose 6-phosphate to saturate non-specific phosphatases. In the latter experiments the following isomers of InsP5 accumulated: D- and/or L-Ins(1,2,3,4,5)P5, plus D- and/or L-Ins(1,2,4,5,6)P5. This demonstration that multiple isomers of InsP5 may be formed in vivo and in vitro by a transformed lymphocyte cell line adds a new level of complexity to the study of inositol polyphosphate metabolism and function. C1 NIEHS,CELLULAR & MOLEC PHARMACOL LAB,INOSITOL LIPID SECT,POB 12233,RES TRIANGLE PK,NC 27709. UNIV WASHINGTON,REG PRIMATE RES CTR,SEATTLE,WA 98195. AFRC,INST ANIM PHYSIOL & GENET RES,CAMBRIDGE CB2 4AT,ENGLAND. RP SHEARS, SB (reprint author), NIEHS,CELLULAR & MOLEC PHARMACOL LAB,INOSITOL LIPID SECT,POB 12233,RES TRIANGLE PK,NC 27709, USA. FU NCRR NIH HHS [RR00166] NR 32 TC 23 Z9 23 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD DEC 1 PY 1991 VL 280 BP 323 EP 329 PN 2 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GU901 UT WOS:A1991GU90100007 PM 1660712 ER PT J AU KALER, SG MARAIA, RJ GAHL, WA AF KALER, SG MARAIA, RJ GAHL, WA TI HUMAN MANGANESE SUPEROXIDE-DISMUTASE IS READILY DETECTABLE BY A COPPER BLOTTING TECHNIQUE SO BIOCHEMICAL MEDICINE AND METABOLIC BIOLOGY LA English DT Article ID AMINO-ACID-SEQUENCE; PROTEINS; RESOLUTION; ELECTROPHORESIS; METALLOTHIONEIN; NITROCELLULOSE; LOCALIZATION; NUCLEOTIDE; BINDING; ZINC RP KALER, SG (reprint author), NICHHD,HUMAN GENET BRANCH,BLDG 10,ROOM 95242,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 26 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 0885-4505 J9 BIOCHEM MED METAB B PD DEC PY 1991 VL 46 IS 3 BP 406 EP 415 DI 10.1016/0885-4505(91)90088-3 PG 10 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA GV783 UT WOS:A1991GV78300011 PM 1793616 ER PT J AU WILLIAMS, TF AF WILLIAMS, TF TI HEALTH-CARE TRENDS FOR OLDER-PEOPLE SO BIOFEEDBACK AND SELF-REGULATION LA English DT Article DE AGING; INTRINSIC AND EXTRINSIC CHARACTERISTICS OF AGING ID WOMEN; AGE RP WILLIAMS, TF (reprint author), NIA,BALTIMORE,MD 21224, USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0363-3586 J9 BIOFEEDBACK SELF-REG JI Biofeedback Self-Regul. PD DEC PY 1991 VL 16 IS 4 BP 337 EP 347 DI 10.1007/BF00999988 PG 11 WC Psychology, Clinical SC Psychology GA GT542 UT WOS:A1991GT54200002 PM 1760456 ER PT J AU MANNARINO, M AF MANNARINO, M TI THE PRESENT AND FUTURE ROLES OF BIOFEEDBACK IN SUCCESSFUL AGING SO BIOFEEDBACK AND SELF-REGULATION LA English DT Article DE GERONTOLOGY; GERIATRICS; AGING; BIOFEEDBACK ID BEHAVIORAL TREATMENT; HYPERTENSION; LIPOLYSIS; SYSTEM; STRESS RP MANNARINO, M (reprint author), NIA,BALTIMORE,MD 21224, USA. NR 15 TC 1 Z9 1 U1 1 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0363-3586 J9 BIOFEEDBACK SELF-REG JI Biofeedback Self-Regul. PD DEC PY 1991 VL 16 IS 4 BP 391 EP 397 DI 10.1007/BF00999992 PG 7 WC Psychology, Clinical SC Psychology GA GT542 UT WOS:A1991GT54200006 PM 1760460 ER PT J AU TOMER, KB PERKINS, JR PARKER, CE DETERDING, LJ AF TOMER, KB PERKINS, JR PARKER, CE DETERDING, LJ TI COAXIAL CONTINUOUS-FLOW FAST-ATOM-BOMBARDMENT FOR HIGHER-MOLECULAR-WEIGHT PEPTIDES - COMPARISON WITH STATIC FAST-ATOM-BOMBARDMENT AND ELECTROSPRAY IONIZATION SO BIOLOGICAL MASS SPECTROMETRY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; MASS-SPECTROMETRY; MICROBORE; BIOMOLECULES; DIGESTS; OPTIMIZATION AB A comparison of coaxial continuous flow fast atom bombardment (FAB) with static FAB and with electrospray ionization (ESI) for the analysis of 'high'-mass peptides (M(r) = 3000-4000) is presented. Sensitivities of the peptides by coaxial continuous flow FAB is nearly an order of magnitude better than by static FAB. Single-scan spectra with good signal-to-noise can be obtained from as little as 200 fmol (by flow injection analysis). Detection limits by ESI mass spectrometry were found to be equivalent to 20 times higher than by coaxial continuous flow FAB on a per mole basis, but 4-20 times lower on a concentration basis, owing to the greater flow per unit time employed in the ESI mass spectrometric experiments. RP TOMER, KB (reprint author), NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709, USA. RI Tomer, Kenneth/E-8018-2013 NR 22 TC 11 Z9 11 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 1052-9306 J9 BIOL MASS SPECTROM JI Biol. Mass Spectrom. PD DEC PY 1991 VL 20 IS 12 BP 783 EP 788 DI 10.1002/bms.1200201207 PG 6 WC Biophysics; Spectroscopy SC Biophysics; Spectroscopy GA GT194 UT WOS:A1991GT19400006 PM 1812988 ER PT J AU YASUI, M OTA, K GARRUTO, RM AF YASUI, M OTA, K GARRUTO, RM TI ALUMINUM DECREASES THE ZINC CONCENTRATION OF SOFT-TISSUES AND BONES OF RATS FED A LOW CALCIUM MAGNESIUM DIET SO BIOLOGICAL TRACE ELEMENT RESEARCH LA English DT Article DE ZINC; MAGNESIUM; CENTRAL NERVOUS SYSTEM; BONE; UNBALANCED MINERAL DIETS; AMYOTROPHIC LATERAL SCLEROSIS ID AMYOTROPHIC LATERAL SCLEROSIS; MINERALS; DEMENTIA; AGE AB The relationship between magnesium (Mg) and zinc (Zn) in soft tissues and bone of rats was studied after administration of unbalanced mineral diets. Minerals and metals in soft tissues and bone were determined using inductively coupled plasma emission spectrometry (ICP). There were significant positive correlations between serum Zn and Mg levels, between serum Zn and Zn content of soft tissues and bone, and between serum Mg levels and Zn content of bone and soft tissues in rats fed unbalanced mineral diets. A significant positive correlation was also found between Zn and Mg content in the lumbar spine and femoral bone of rats. It appears that altered bone mineralization induced by unbalanced mineral diets leads to mobilization of Mg and Zn from rat bones in similar ways. C1 WAKAYAMA MED COLL, DEPT LAB MED, WAKAYAMA 640, JAPAN. NIH, BETHESDA, MD 20892 USA. RP WAKAYAMA MED COLL, DIV NEUROL DIS, WAKAYAMA 640, JAPAN. NR 21 TC 15 Z9 15 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0163-4984 EI 1559-0720 J9 BIOL TRACE ELEM RES JI Biol. Trace Elem. Res. PD DEC PY 1991 VL 31 IS 3 BP 293 EP 304 DI 10.1007/BF02990198 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA GY687 UT WOS:A1991GY68700008 PM 1723618 ER PT J AU JOHNSTON, LA DONOGHUE, AM OBRIEN, SJ WILDT, DE AF JOHNSTON, LA DONOGHUE, AM OBRIEN, SJ WILDT, DE TI RESCUE AND MATURATION INVITRO OF FOLLICULAR OOCYTES COLLECTED FROM NONDOMESTIC FELID SPECIES SO BIOLOGY OF REPRODUCTION LA English DT Article ID DOMESTIC CAT; DEVELOPMENTAL COMPETENCE; FERTILIZATION INVITRO; GENETIC-VARIATION; CHEETAH; EJACULATE; LEOPARD; BENGALENSIS; CAPACITY; TRAITS AB The potential for rescuing immature oocytes from the ovaries of females of rare felid species which die or undergo medical ovariohysterectomy was evaluated. Ovaries were recovered from 13 species representing 35 individuals in good-to-poor health. Although the majority of females were 10 yr of age or older and in fair-to-poor health, a total of 846 oocytes were recovered of which 608 (71.9%) were classified as fair-to-excellent quality. One hundred of these oocytes were used for initial maturation classification and as parthogenetic controls. Overall, of the 508 fair-to-excellent quality oocytes placed in culture, 164 (32.3%) matured to metaphase II in vitro. For species in which 3 or more individuals yielded oocytes, mean oocyte maturation rates were as follows: 36.2%, tiger; 27.9% leopard; and 8.3%, cheetah. In vitro insemination of oocytes resulted in fertilization (2 polar bodies, 2 pronuclei, or cleavage) rates of 9.1 % to 28.6% (leopard) using homologous fresh spermatozoa and 4.0% (lion) to 40.0% (puma) using homologous frozen-thawed spermatozoa. Inseminations using heterologous (domestic cat) spermatozoa also resulted in fertilized oocytes in the tiger, leopard, snow leopard, puma, serval, and Geoffroy's cat (range in fertilization rate, 5.0% for leopard to 46.2% for puma). Cleaved embryos resulted from the insemination of leopard oocytes with homologous sperm (n = 1 embryo) and puma oocytes with domestic cat sperm (n = 3 embryos). These results demonstrate that immature ovarian oocytes from rare felid species can be stimulated to mature in vitro despite an excision-to-culture interval as long as 36 h. These oocytes are capable of fertilization in vitro, although fertilization rates do not approach those achieved in parallel studies in domestic cats. Our observations of successful cross-species sperm-oocyte interaction in vitro (including the production of cleaved embryos) confirms that the oocytes of certain felid species have not developed mechanisms for excluding penetration or fertilization by heterologous felid spermatozoa. C1 SMITHSONIAN INST,NATL ZOOL PK,WASHINGTON,DC 20008. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. FU NICHD NIH HHS [HD 23853] NR 34 TC 64 Z9 65 U1 2 U2 6 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD DEC PY 1991 VL 45 IS 6 BP 898 EP 906 DI 10.1095/biolreprod45.6.898 PG 9 WC Reproductive Biology SC Reproductive Biology GA GR668 UT WOS:A1991GR66800014 PM 1805993 ER PT J AU BAKER, SG FREEDMAN, LS PARMAR, MKB AF BAKER, SG FREEDMAN, LS PARMAR, MKB TI USING REPLICATE OBSERVATIONS IN OBSERVER AGREEMENT STUDIES WITH BINARY ASSESSMENTS SO BIOMETRICS LA English DT Article DE CATEGORICAL DATA; EM ALGORITHM; LATENT VARIABLES ID LATENT CLASS ANALYSIS; MODEL; TESTS AB By introducing replicate observations into observer agreement studies, one can obtain better measures of observer agreement than heretofore possible. New methodology based on the analysis of latent variables allows a separation of within- and between-observer variation for binary measures of assessment among pairs of observers. Maximum likelihood estimation and hypothesis testing are discussed. The methodology is illustrated using data on the assessment of dysplasia by pathologists. C1 MRC,CANC TRIALS OFF,CAMBRIDGE CB2 2BW,ENGLAND. RP BAKER, SG (reprint author), NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,EXECUT PLAZA N,BETHESDA,MD 20892, USA. NR 24 TC 25 Z9 25 U1 0 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 DEC PY 1991 VL 47 IS 4 BP 1327 EP 1338 DI 10.2307/2532389 PG 12 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA GY512 UT WOS:A1991GY51200009 PM 1786322 ER PT J AU LIN, KH CHENG, SY AF LIN, KH CHENG, SY TI AN EFFICIENT METHOD TO PURIFY ACTIVE EUKARYOTIC PROTEINS FROM THE INCLUSION-BODIES IN ESCHERICHIA-COLI SO BIOTECHNIQUES LA English DT Note ID PURIFICATION; HORMONE C1 NCI,MOLEC BIOL LAB,BLDG 37,ROOM 4B09,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 6 TC 83 Z9 84 U1 0 U2 1 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD DEC PY 1991 VL 11 IS 6 BP 748 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GU031 UT WOS:A1991GU03100013 PM 1809329 ER PT J AU DUBOIS, CM RUSCETTI, FW KELLER, JR OPPENHEIM, JJ HESTDAL, K CHIZZONITE, R NETA, R AF DUBOIS, CM RUSCETTI, FW KELLER, JR OPPENHEIM, JJ HESTDAL, K CHIZZONITE, R NETA, R TI INVIVO INTERLEUKIN-1 (IL-1) ADMINISTRATION INDIRECTLY PROMOTES TYPE-II IL-1 RECEPTOR EXPRESSION ON HEMATOPOIETIC BONE-MARROW CELLS - NOVEL MECHANISM FOR THE HEMATOPOIETIC EFFECTS OF IL-1 SO BLOOD LA English DT Article ID COLONY-STIMULATING ACTIVITY; GRANULOCYTE-MACROPHAGE; PROGENITOR CELLS; B-CELL; MICE; MURINE; FIBROBLASTS; GRANULOPOIESIS; INFLAMMATION; NEUTROPHILS C1 HOFFMANN LA ROCHE INC,DEPT IMMUNOPHARMACOL & MOLEC GENET,NUTLEY,NJ 07110. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701. ARMED FORCES RADIOBIOL RES INST,DEPT EXPTL HEMATOL,BETHESDA,MD 20814. DYNCORP,PROGRAM RESOURCES INC,FREDERICK,MD. NR 43 TC 27 Z9 28 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 1991 VL 78 IS 11 BP 2841 EP 2847 PG 7 WC Hematology SC Hematology GA GR781 UT WOS:A1991GR78100006 PM 1720037 ER PT J AU GARTENHAUS, RB WONGSTAAL, F KLOTMAN, ME AF GARTENHAUS, RB WONGSTAAL, F KLOTMAN, ME TI THE PROMOTER OF HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I IS REPRESSED BY THE IMMEDIATE-EARLY GENE REGION OF HUMAN CYTOMEGALOVIRUS IN PRIMARY BLOOD-LYMPHOCYTES SO BLOOD LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG-TERMINAL REPEAT; CHLORAMPHENICOL ACETYLTRANSFERASE; TRANSCRIPTIONAL ACTIVATION; EXPRESSION; ANTIBODIES; IDENTIFICATION; PARTICLES; INFECTION; SEQUENCES C1 UNIV SAN DIEGO,DEPT MED,SAN DIEGO,CA 92110. UNIV SAN DIEGO,DEPT BIOL,SAN DIEGO,CA 92110. DUKE UNIV,DEPT MED,DURHAM,NC 27706. VET ADM MED CTR,DURHAM,NC 27705. RP GARTENHAUS, RB (reprint author), NCI,TUMOR CELL BIOL LAB,BLDG 37,ROOM 6A09,BETHESDA,MD 20892, USA. RI klotman, mary/A-1921-2016 NR 35 TC 13 Z9 13 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 1991 VL 78 IS 11 BP 2956 EP 2961 PG 6 WC Hematology SC Hematology GA GR781 UT WOS:A1991GR78100021 PM 1659469 ER PT J AU SIRIGU, A DUHAMEL, JR PONCET, M AF SIRIGU, A DUHAMEL, JR PONCET, M TI THE ROLE OF SENSORIMOTOR EXPERIENCE IN OBJECT RECOGNITION - A CASE OF MULTIMODAL AGNOSIA SO BRAIN LA English DT Article ID OPTIC APHASIA; SEMANTIC SYSTEMS; VISUAL AGNOSIA; IMPAIRMENT; LANGUAGE; VISION; MONKEY AB Object recognition was studied in a 19-yr-old male patient who presented severe multimodal amnesia and agnosia without significant intellectual, linguistic or perceptual deficits. Bilateral temporal lobe lesions involved medial, polar and anterior infero-temporal structures. Although visual recognition was impaired to various extents for all categories of objects, preservation of certain capacities were demonstrated. In particular, the patient was able to determine specifically how to manipulate certain objects, in spite of his incapacity to define their function or their context of utilization. It is argued that object recognition involves different processing modes such that when direct access to representations of an object is impaired, sensorimotor information activated via alternative cortical and subcortical pathways may provide a limited mechanism for recognition. C1 NEI,SENSORIMOTOR RES LAB,BETHESDA,MD 20892. CHU TIMONE,DEPT NEUROPSYCHOL & REEDUC LANGAGE,F-13385 MARSEILLE,FRANCE. RP SIRIGU, A (reprint author), NINCDS,COGNIT NEUROSCI SECT,BLDG 10,ROOM 5C422,BETHESDA,MD 20892, USA. NR 35 TC 204 Z9 206 U1 2 U2 11 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0006-8950 J9 BRAIN JI Brain PD DEC PY 1991 VL 114 BP 2555 EP 2573 DI 10.1093/brain/114.6.2555 PN 6 PG 19 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA HC611 UT WOS:A1991HC61100011 PM 1782531 ER PT J AU VOCCI, FJ AF VOCCI, FJ TI THE NECESSITY AND UTILITY OF ABUSE LIABILITY EVALUATIONS IN HUMAN-SUBJECTS SO BRITISH JOURNAL OF ADDICTION LA English DT Review ID DRUG PREFERENCE; MORPHINE-LIKE; DIAZEPAM; BUSPIRONE; DOG AB Assessments of the abuse potential of psychoactive drugs in preclinical and clinical studies are used in regulatory decision making process in the United States under the Controlled Substance Act (CSA) and the Federal Food, Drug, and Cosmetic Act (FD & C Act). Two types of drugs are evaluated in abuse potential studies, those being developed for a therapeutic indication by the pharmaceutical industry and illicitly manufactured 'street drugs' of abuse. Only the former will be considered here. In the case of drugs being pursued for marketing or are amendable to study in human subjects and are of scientific, medical, or regulatory interest, preclinical data may be inadequate for drug scheduling and marketing decisions. Preclinical data assessment can suggest hypotheses which must be validated in clinical studies. Moreover, there are limitations to the feasibility of evaluating certain drugs/dosage forms in preclinical studies. Thus, clinical studies are needed for the following scientific reasons: to validate preclinical hypotheses; to assess the time-course of subjective effects as a function of dose and route of administration; to evaluate the generalizability of drug liking in different human subject populations; and to evaluate the effects of drugs on cognitive and affective processes. Clinical studies are also needed if a claim is made regarding reduced or no abuse potential; and lack of additive or potentiative effects with alcohol. RP VOCCI, FJ (reprint author), NIDA,DIV MED DEV,DEV THERAPEUT BRANCH,5600 FISHERS LANE,ROOM 11A-55,ROCKVILLE,MD 20857, USA. NR 24 TC 2 Z9 2 U1 0 U2 0 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0952-0481 J9 BRIT J ADDICT PD DEC PY 1991 VL 86 IS 12 BP 1537 EP 1542 PG 6 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA GW694 UT WOS:A1991GW69400005 PM 1786484 ER PT J AU HENNINGFIELD, JE COHEN, C HEISHMAN, SJ AF HENNINGFIELD, JE COHEN, C HEISHMAN, SJ TI DRUG SELF-ADMINISTRATION METHODS IN ABUSE LIABILITY EVALUATION SO BRITISH JOURNAL OF ADDICTION LA English DT Article ID INTRAVENOUS NICOTINE; CIGARETTE-SMOKING; OPERANT ANALYSIS; ALCOHOLICS; BEHAVIOR; HUMANS AB The human drug self-administration paradigm is an extension of the animal model developed in the 1960s. The paradigm can be used to investigate the determinants and correlates of drug-seeking and drug-taking behavior and has proven useful in the development of medications for treating drug dependence. This paper describes the basic components of the human self-administration model and discusses studies that illustrate some of its applications, including assessment of the reinforcing effects of drugs, analysis of behavioral and pharmacological mechanisms of drug self-administration and measurement of the abuse liability, behavioral toxicity, and aversive effects of drugs. Some of the strengths and limitations of using the paradigm with human research subjects are also presented. It is concluded that the drug self-administration model should not replace other measures of abuse liability testing in humans, but should be incorporated into comprehensive programs of drug abuse assessment wherever possible. RP HENNINGFIELD, JE (reprint author), NIDA,ADDICT RES CTR,CLIN PHARMACOL BRANCH,POB 5180,BALTIMORE,MD 21224, USA. NR 31 TC 26 Z9 26 U1 1 U2 2 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0952-0481 J9 BRIT J ADDICT PD DEC PY 1991 VL 86 IS 12 BP 1571 EP 1577 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA GW694 UT WOS:A1991GW69400010 PM 1786489 ER PT J AU GRALNICK, HR WILLIAMS, S MCKEOWN, LP CONNAGHAN, G SHAFER, B HANSMANN, K MAGRUDER, L VAIL, M AF GRALNICK, HR WILLIAMS, S MCKEOWN, LP CONNAGHAN, G SHAFER, B HANSMANN, K MAGRUDER, L VAIL, M TI PLATELET ACTIVATION AND ALPHA GRANULE SECRETION IN TYPE-IIB VONWILLEBRANDS DISEASE SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article ID MEMBRANE-PROTEIN; MONOCLONAL-ANTIBODY; PLASMA-MEMBRANE; AGGREGATION; NEUTROPHILS; FIBRINOGEN; GMP-140 AB Type IIB von Willebrand disease is characterized by enhanced ristocetin-induced platelet aggregation, spontaneous platelet aggregation, thrombocytopenia and the absence of the largest plasma von Willebrand factor (vWf) multimers. The absence of the largest plasma vWf multimers is related to their enhanced binding to platelets. The abnormal affinity of the IIB von Willebrand factor to platelets results in thrombocytopenia, but the mechanism is not known. We have studied the platelets from three patients with type IIB von Willebrand disease and have found evidence of platelet activation and alpha granule secretion as defined by increased amounts of von Willebrand factor, fibrinogen and the alpha granule protein PADGEM/GMP-140 on the surface of these platelets. The degree of thrombocytopenia appears to be directly related to the number of platelets with fibrinogen bound to the surface. PADGEM/GMP-140, an alpha granule membrane protein, fuses with the platelet plasma membrane after activation and is a site on platelets which binds to neutrophils or monocytes. This alpha granule protein may play an additional role in platelet clearance and thrombocytopenia in type IIB von Willebrand disease. This may, in part, explain the absence of thromboembolic phenomena despite the presence of activated platelets in patients with type IIB von Willebrand disease. RP GRALNICK, HR (reprint author), NIH,CTR CLIN,HEMATOL SERV,ROOM 2C390,BETHESDA,MD 20892, USA. NR 22 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 1991 VL 79 IS 4 BP 618 EP 623 DI 10.1111/j.1365-2141.1991.tb08090.x PG 6 WC Hematology SC Hematology GA GV281 UT WOS:A1991GV28100013 PM 1722992 ER PT J AU SIMON, R AF SIMON, R TI THE NCI PROGRAM OF THERAPEUTIC RESEARCH SO BULLETIN DU CANCER LA English DT Article; Proceedings Paper CT 3RD WORKSHOP OF THE ASSOC-POUR-LA-RECHERCHE-THERAPEUTIQUE-ANTICANCEREUSE - THERAPEUTIC TRIALS IN ONCOLOGY : SCIENTIFIC CONCEPTS, METHODOLOGY AND NEW DRUGS CY OCT 19-20, 1989 CL PARIS, FRANCE SP ASSOC RECH THERAPEUT ANTICANC RP SIMON, R (reprint author), NCI,BIOMETR RES BRANCH,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 0007-4551 J9 B CANCER JI Bull. Cancer PD DEC PY 1991 VL 78 IS 12 BP 1105 EP 1108 PG 4 WC Oncology SC Oncology GA GZ452 UT WOS:A1991GZ45200003 PM 1786423 ER PT J AU REY, C SHIMIZU, M COLLINS, B GLIMCHER, MJ AF REY, C SHIMIZU, M COLLINS, B GLIMCHER, MJ TI RESOLUTION-ENHANCED FOURIER-TRANSFORM INFRARED-SPECTROSCOPY STUDY OF THE ENVIRONMENT OF PHOSPHATE ION IN THE EARLY DEPOSITS OF A SOLID-PHASE OF CALCIUM-PHOSPHATE IN BONE AND ENAMEL AND THEIR EVOLUTION WITH AGE .2. INVESTIGATIONS IN THE NU-3 PO4 DOMAIN SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE INFRARED SPECTROSCOPY; BONE; ENAMEL; CARBONATE; PHOSPHATE ID APATITES AB Resolution-enhanced Fourier Transform Infrared (FTIR) spectra of early mineral deposits in enamel and bone show bands at 1020, 1100, 1110, 1125, and 1145 cm-1 in the nu-3PO4 domain which do not belong to well crystallized stoichiometric hydroxyapatite. Bands at 1020 and 1100 cm-1 have been shown to occur in nonstoichiometric apatites containing HPO4(2-) ions and the weak band at 1145 cm-1 has been assigned to HPO4(2-) ions. Though the bands at 1110 and 1125 cm-1 have not been found in any well crystallized apatite, they are present in newly precipitated apatite. These latter bands disappear progressively during maturation in biological as well as synthetic samples, and partial dissolution of synthetic apatites shows that they belong to species that exhibit an inhomogeneous distribution in the mineral, and that are the first to be solubilized. Comparison of the FTIR spectra of biological apatites with those of synthetic, nonapatitic-containing phosphate minerals shows that the presence of these bands does not arise from nonapatitic, well-defined phases; they are due to the local environment of phosphate ions which may possibly be loosely related or perhaps unrelated to the phosphate groups present in the well-crystallized nonapatitic calcium phosphates. Resolution-enhanced FTIR affords a very precise characterization of the mineral phases which may be very useful in characterizing pathological deposits of Ca-P mineral phases. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,STUDY SKELETAL DISORDERS & REHABIL LAB,300 LONGWOOD AVE,BOSTON,MA 02115. TSURUMI UNIV,SCH DENT MED,YOKOHAMA,KANAGAWA,JAPAN. NIEHS,DEPT CHEM,RES TRIANGLE PK,NC 27709. NR 19 TC 199 Z9 199 U1 1 U2 33 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 DEC PY 1991 VL 49 IS 6 BP 383 EP 388 DI 10.1007/BF02555847 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GP407 UT WOS:A1991GP40700005 PM 1818762 ER PT J AU BIANCO, P FISHER, LW YOUNG, MF TERMINE, JD ROBEY, PG AF BIANCO, P FISHER, LW YOUNG, MF TERMINE, JD ROBEY, PG TI EXPRESSION OF BONE SIALOPROTEIN (BSP) IN DEVELOPING HUMAN TISSUES SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE BONE SIALOPROTEIN; DEVELOPING BONE; NONCOLLAGENOUS PROTEINS; INSITU HYBRIDIZATION; OSTEOBLAST; OSTEOCLAST; CELL ADHESION ID INSITU HYBRIDIZATION; DEVELOPMENTAL EXPRESSION; OSTEONECTIN; LOCALIZATION; RAT; PHOSPHOPROTEIN; PROTEOGLYCAN; OSTEOPONTIN; SULFATE; PROTEIN AB Bone sialoprotein (BSP) and its messenger RNA were localized in developing human skeletal and nonskeletal tissues by means of immunohistochemistry and in situ hybridization. Both protein and mRNA were found in mature, bone-forming cells but not in their immature precursors. In addition, osteoclasts displayed positive immunostaining and high densities of autoradiographic grains by in situ hybridization experiments. BSP was expressed in fetal epiphyseal cartilage cells, particularly in hypertrophic chondrocytes of growth plates. Though neither the protein nor the mRNA were identified in a variety of other connective and nonconnective tissues, an unexpected finding was the expression of BSP in the trophoblast cells of placenta. These findings show that BSP is primarily an osteoblast-derived component of the bone matrix expressed at late stages of differentiation. We have also found that osteoclasts produce BSP, possibly as a mediator of cell attachment to bone. C1 NIDR,BONE RES BRANCH,BLDG 30,ROOM 106,BETHESDA,MD 20892. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 22 TC 317 Z9 322 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 DEC PY 1991 VL 49 IS 6 BP 421 EP 426 DI 10.1007/BF02555854 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GP407 UT WOS:A1991GP40700012 PM 1818768 ER PT J AU SCHWARTZENTRUBER, DJ WHITE, DE ZWEIG, MH WEINTRAUB, BD ROSENBERG, SA AF SCHWARTZENTRUBER, DJ WHITE, DE ZWEIG, MH WEINTRAUB, BD ROSENBERG, SA TI THYROID-DYSFUNCTION ASSOCIATED WITH IMMUNOTHERAPY FOR PATIENTS WITH CANCER SO CANCER LA English DT Article ID INTERLEUKIN-2 THERAPY; ALPHA-INTERFERON; HYPOTHYROIDISM; CELLS AB The authors performed a prospective study to evaluate thyroid dysfunction in 130 patients with cancer who were receiving interleukin-2 (IL-2)-based immunotherapy. Primary hypothyroidism was the most common abnormality, occurring in 12% of patients before, 38% during, and 23% after immunotherapy. Hyperthyroidism occurred in 1%, 4%, and 7% of patients at those time intervals. Among patients initially euthyroid (n = 111), primary hypothyroidism developed in 32% during and 14% after immunotherapy, persisting a median of 54 days. Three patients required levothyroxine. Hyperthyroidism developed in 2% of patients during immunotherapy and 6% after. Thyroid dysfunction was not a function of sex, diagnosis, type of treatment, or response to immunotherapy. Elevated titers of antithyroglobulin and antithyroid microsomal antibodies were detected after treatment in 9% and 7%, respectively, of all patients without prior antibody abnormalities and did not correlate with response to therapy. The high incidence of therapy-induced thyroid dysfunction suggests that thyroid function should be carefully monitored in all patients receiving IL-2-based immunotherapy. C1 NIDDKD,BETHESDA,MD. NCI,CTR CLIN,BETHESDA,MD 20892. RP SCHWARTZENTRUBER, DJ (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B51,BETHESDA,MD 20892, USA. NR 16 TC 55 Z9 55 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 DEC 1 PY 1991 VL 68 IS 11 BP 2384 EP 2390 DI 10.1002/1097-0142(19911201)68:11<2384::AID-CNCR2820681109>3.0.CO;2-A PG 7 WC Oncology SC Oncology GA GQ105 UT WOS:A1991GQ10500008 PM 1933775 ER PT J AU GUADAGNI, F ROSELLI, M AMATO, T COSIMELLI, M MANNELLA, E PERRI, P ABBOLITO, MR CAVALIERE, R COLCHER, D GREINER, JW SCHLOM, J AF GUADAGNI, F ROSELLI, M AMATO, T COSIMELLI, M MANNELLA, E PERRI, P ABBOLITO, MR CAVALIERE, R COLCHER, D GREINER, JW SCHLOM, J TI TUMOR-ASSOCIATED GLYCOPROTEIN-72 SERUM LEVELS COMPLEMENT CARCINOEMBRYONIC ANTIGEN LEVELS IN MONITORING PATIENTS WITH GASTROINTESTINAL CARCINOMA - A LONGITUDINAL-STUDY SO CANCER LA English DT Article ID MONOCLONAL-ANTIBODY B72.3; COLORECTAL-CANCER; TAG-72; REACTIVITY; CEA; ADENOCARCINOMAS; PROGNOSIS; COLON AB Eighty-two patients diagnosed with gastrointestinal (GI) adenocarcinoma were evaluated before and for 26 months after primary tumor resection for the presence of two serum tumor markers: tumor-associated glycoprotein-72 (TAG-72) and carcinoembryonic antigen (CEA). Elevated TAG-72 and CEA serum levels were found preoperatively in 32 (39%) and 34 (41.5%) of the 82 patients, respectively. The percentage of patients with elevated serum levels of either TAG-72 or CEA was 56.1% (46 of 82). Twelve (15%) patients who had normal CEA serum levels had elevated TAG-72 serum levels, and conversely, serum from 14 (17%) patients who were TAG-72 negative were CEA positive. Forty-five of the 82 patients were diagnosed with advanced disease (i.e., Stages C and D for colorectal, Stages III and IV for stomach), and 29 (64.4%) and 26 (57.8%) of those patients had elevated serum levels of TAG-72 or CEA, respectively. Elevated levels of either TAG-72 or CEA, however, were found in sera of 82.2% of patients with advanced GI cancer, which is an increase of 24.4% over the use of CEA antigen alone as a marker of disease. The measurement of both TAG-72 and CEA may improve the diagnosis of patients with GI malignant disease due to the apparent complementary association which exists between these tumor markers. Serum TAG-72 and CEA levels were monitored in 31 patients for varying lengths of time after resection of the carcinoma; 11 patients developed recurrent disease. Sera from nine of 11 (81.8%) of these patients had elevated TAG-72 levels and six of 11 (54.5%) had elevated CEA levels. Tumor marker elevations were observed either before (35 to 166 days) or at the time of diagnosis of recurrence. The elevation of one or both markers correlated with the clinical status in ten of 11 (90.9%) patients with recurrence. In addition, 20 patients who were clinically free of disease after more than 700 days' follow-up had normal serum levels of both TAG-72 and CEA. These findings suggest that the combined use of serum TAG-72 and CEA measurements may improve detection of recurrence in patients with GI cancer and may be useful in the postsurgical management of GI adenocarcinoma patients. C1 NCI,TUMOR IMMUNOL & BIOL,BLDG 10,ROOM 8B07,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NCI,CELLULAR METAB & PHARMACOKINET LAB,BETHESDA,MD 20892. DEPT CLIN PATHOL,ROME,ITALY. NCI,DEPT SURG,BETHESDA,MD 20892. UNIV NEBRASKA,MED CTR,DEPT PATHOL MICROBIOL,OMAHA,NE 68105. RI Guadagni, Fiorella/J-4432-2013 OI Guadagni, Fiorella/0000-0003-3652-0457 NR 24 TC 36 Z9 39 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD DEC 1 PY 1991 VL 68 IS 11 BP 2443 EP 2450 DI 10.1002/1097-0142(19911201)68:11<2443::AID-CNCR2820681120>3.0.CO;2-2 PG 8 WC Oncology SC Oncology GA GQ105 UT WOS:A1991GQ10500019 PM 1933781 ER PT J AU YANCIK, R RIES, LG AF YANCIK, R RIES, LG TI CANCER IN THE AGED - AN EPIDEMIOLOGIC PERSPECTIVE ON TREATMENT ISSUES SO CANCER LA English DT Article; Proceedings Paper CT NATIONAL WORKSHOP OF THE AMERICAN CANCER SOC : CANCER CONTROL AND THE OLDER PERSON CY MAR 14-16, 1991 CL ATLANTA, GA SP AMER CANC SOC ID DIAGNOSIS; PATIENT; VARIES; BREAST AB Persons 65 years of age and older bear the greatest burden of cancer; 55% of all malignancies occur in this age group. Sixty-seven percent of all cancer deaths occurred in this population in 1988. This article describes the magnitude of the cancer problem for this age group according to major cancers (colon, rectum, lung/bronchus, pancreas, stomach, urinary bladder, breast, and prostate). Data are cast against the demographics of aging in the United States. These facts emphasize an urgent need to concentrate more attention on problems unique to the elderly for early detection, diagnosis, and treatment. Information gaps are also identified. C1 NCI,DIV CANC PREVENT & CONTROL,CANC STAT BRANCH,SURVEILLANCE PROGRAM,BETHESDA,MD 20892. RP YANCIK, R (reprint author), NIA,OFF DIRECTOR,FED BLDG,ROOM 6C02,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 16 TC 83 Z9 83 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD DEC 1 PY 1991 VL 68 IS 11 SU S BP 2502 EP 2510 DI 10.1002/1097-0142(19911201)68:11+<2502::AID-CNCR2820681504>3.0.CO;2-Q PG 9 WC Oncology SC Oncology GA GQ294 UT WOS:A1991GQ29400003 PM 1933793 ER PT J AU HOLMES, FF WILSON, J BLESCH, KS KAESBERG, PR MILLER, R SPROTT, R AF HOLMES, FF WILSON, J BLESCH, KS KAESBERG, PR MILLER, R SPROTT, R TI BIOLOGY OF CANCER AND AGING SO CANCER LA English DT Article; Proceedings Paper CT NATIONAL WORKSHOP OF THE AMERICAN CANCER SOC : CANCER CONTROL AND THE OLDER PERSON CY MAR 14-16, 1991 CL ATLANTA, GA SP AMER CANC SOC AB The greatest risk factor for cancer is aging. Human cancer incidence increases exponentially with advancing age. Cancer growth rate and potential for metastatic spread may be influenced by age-specific change in host response. Because cancer and aging are, thus, inextricably linked, the American Cancer Society should encourage submission of research proposals that address the mechanisms of aging and how aging alters cancer development. C1 AMER CANC SOC,DEPT DETECT & TREATMENT,ATLANTA,GA. UNIV ILLINOIS,SCH PUBL HLTH,CHICAGO,IL 60680. UNIV WISCONSIN,INST AGING,MADISON,WI 53706. UNIV MICHIGAN,DEPT PATHOL,ANN ARBOR,MI 48109. NIA,BETHESDA,MD 20892. RP HOLMES, FF (reprint author), UNIV KANSAS,MED CTR,39TH & RAINBOW BLVD,KANSAS CITY,KS 66103, USA. NR 6 TC 10 Z9 10 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 DEC 1 PY 1991 VL 68 IS 11 SU S BP 2525 EP 2526 DI 10.1002/1097-0142(19911201)68:11+<2525::AID-CNCR2820681508>3.0.CO;2-3 PG 2 WC Oncology SC Oncology GA GQ294 UT WOS:A1991GQ29400007 PM 1933796 ER PT J AU BALDUCCI, L ADES, T CARBONE, PP FRIEDMAN, M FULMER, T GALAKOTOS, A YANCIK, R AF BALDUCCI, L ADES, T CARBONE, PP FRIEDMAN, M FULMER, T GALAKOTOS, A YANCIK, R TI ISSUES IN TREATMENT SO CANCER LA English DT Article; Proceedings Paper CT NATIONAL WORKSHOP OF THE AMERICAN CANCER SOC : CANCER CONTROL AND THE OLDER PERSON CY MAR 14-16, 1991 CL ATLANTA, GA SP AMER CANC SOC AB The Committee on Treatment acknowledged the paucity of information related to the management of cancer in older patients and identified short-term and long-term efforts to study these issues. Short-term efforts should focus on effects of cancer and cancer treatment on survival and quality of life, efficacy and toxicity of antineoplastic therapy, barriers to adequate treatment, alternative settings of cancer care, and special supportive care needs. Long-term efforts should focus on unique features of cancer in older patients, long-term effects of cancer and cancer treatment, and prevention and detection of new primary malignancies. The Committee recognized that our recent advances in cancer treatment including palliative surgery, limited surgery, radiosurgery, and antidotes to drug toxicity may improve the tolerance of antineoplastic therapy by older patients and be beneficial in terms of survival and quality of life. C1 AMER CANC SOC,DEPT NURSING & PATIENT SERV,ATLANTA,GA. UNIV WISCONSIN,CTR CLIN CANC,MADISON,WI 53706. NCI,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892. YALE UNIV,COLL NURSING,NEW HAVEN,CT 06520. WASHINGTON UNIV,BARNES HOSP,DEPT CLIN OBSTET GYNECOL,CHESTERFIELD,MO. NIA,BETHESDA,MD 20892. RP BALDUCCI, L (reprint author), UNIV S FLORIDA,JAMES A HALEY VET HOSP,ONCOL SECT 111N,1300 BRUCE B DOWNS BLVD,TAMPA,FL 33612, USA. NR 0 TC 9 Z9 9 U1 0 U2 6 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 DEC 1 PY 1991 VL 68 IS 11 SU S BP 2527 EP 2529 DI 10.1002/1097-0142(19911201)68:11+<2527::AID-CNCR2820681509>3.0.CO;2-V PG 3 WC Oncology SC Oncology GA GQ294 UT WOS:A1991GQ29400008 PM 1933797 ER PT J AU METTLIN, C BONFIGLIO, J BERG, RL NELSON, G NEWELL, GR PATTERSON, WB RICHARDSON, J RIMER, B SORENSON, A WARNECKE, R AF METTLIN, C BONFIGLIO, J BERG, RL NELSON, G NEWELL, GR PATTERSON, WB RICHARDSON, J RIMER, B SORENSON, A WARNECKE, R TI PREVENTION AND DETECTION IN OLDER PERSONS SO CANCER LA English DT Article; Proceedings Paper CT NATIONAL WORKSHOP OF THE AMERICAN CANCER SOC : CANCER CONTROL AND THE OLDER PERSON CY MAR 14-16, 1991 CL ATLANTA, GA SP AMER CANC SOC AB Older persons are appropriate targets for a range of prevention and early detection interventions, however, greater emphasis should be given to structuring the delivery of prevention and detection services to the special needs of this population. This may require research and program development to reach older persons in the most effective and cost-effective manner. The American Cancer Society and other program efforts must accommodate the heterogeneity and special needs of segments of the older population. Racial and cultural minorities, impoverished persons, the cognitively impaired, and the physically impaired are four groups requiring special attention. Early detection guidelines specific to older persons should be developed. C1 AMER CANC SOC,DEPT DETECT & TREATMENT,ATLANTA,GA. UNIV ROCHESTER,SCH MED,DEPT COMMUNITY & PREVENT MED,ROCHESTER,NY 14627. CTR DIS CONTROL,CTR CHRON DIS PREVENT & HLTH PROMOT,ATLANTA,GA 30333. UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT CANC PREVENT & CONTROL,HOUSTON,TX 77030. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115. UNIV SO CALIF,SCH MED,NORRIS COMPREHENS CANC CTR,DEPT PREVENT MED,LOS ANGELES,CA 90033. FOX CHASE CANC INST,DEPT POPULAT SCI BEHAV RES,CHELTENHAM,PA. NIA,BIOL AGING PROGRAM,NUTR PROGRAM,BETHESDA,MD 20892. SURVEY RES LAB,CHICAGO,IL. RP METTLIN, C (reprint author), NEW YORK STATE DEPT HLTH,ROSWELL PK MEM INST,666 ELM ST,BUFFALO,NY 14263, USA. NR 0 TC 5 Z9 5 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD DEC 1 PY 1991 VL 68 IS 11 SU S BP 2530 EP 2533 DI 10.1002/1097-0142(19911201)68:11+<2530::AID-CNCR2820681510>3.0.CO;2-3 PG 4 WC Oncology SC Oncology GA GQ294 UT WOS:A1991GQ29400009 PM 1933798 ER PT J AU VACHON, MLS ROBINOVITCH, A BURKLOW, J GANZ, P HERMANN, J JOSEPH, R KANE, RA AF VACHON, MLS ROBINOVITCH, A BURKLOW, J GANZ, P HERMANN, J JOSEPH, R KANE, RA TI CANCER CONTROL AND THE OLDER PERSON - PSYCHOSOCIAL ISSUES SO CANCER LA English DT Article ID PREFERENCES AB Three major areas related to psychosocial issues pertinent to the provision of cancer control services to older people have been delineated. These are values and medical decision making, psychosocial barriers to screening and access to care and services, and quality of life, including rehabilitation. These areas are explored, salient issues are defined, and specific questions and areas for consideration in future research are identified at the macro and micro levels. C1 AMER CANC SOC, DEPT NURSING & PATIENT SERV, ATLANTA, GA USA. NCI, OFF CANC COMMUN, OLDER AMERICANS PROGRAM, BETHESDA, MD 20892 USA. UNIV CALIF LOS ANGELES, SAN FERNANDO VALLEY PROGRAM, DEPT HEMATOL ONCOL, LOS ANGELES, CA 90024 USA. VET ADM MED CTR BRENTWOOD, LOS ANGELES, CA 90073 USA. FOX CHASE CANC INST, DEPT SOCIAL WORK SERV, PHILADELPHIA, PA 19111 USA. MED COLL PENN, DEPT MED, PHILADELPHIA, PA 19129 USA. UNIV MINNESOTA, DEPT HLTH SERV RES & POLICY, MINNEAPOLIS, MN 55455 USA. RP VACHON, MLS (reprint author), CLARKE INST PSYCHIAT, 250 COLL ST, TORONTO M4X 1B3, ONTARIO, CANADA. NR 9 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD DEC 1 PY 1991 VL 68 IS 11 SU S BP 2534 EP 2539 DI 10.1002/1097-0142(19911201)68:11+<2534::AID-CNCR2820681511>3.0.CO;2-P PG 6 WC Oncology SC Oncology GA GQ294 UT WOS:A1991GQ29400010 PM 1933799 ER PT J AU THIELE, CJ AF THIELE, CJ TI BIOLOGY OF PEDIATRIC PERIPHERAL NEUROECTODERMAL TUMORS SO CANCER AND METASTASIS REVIEWS LA English DT Review DE NEUROBLASTOMA; NEUROEPITHELIOMA; EWINGS SARCOMA; RETINOIC ACID; DIFFERENTIATION ID HUMAN NEURO-BLASTOMA; ACUTE PROMYELOCYTIC LEUKEMIA; TRANS RETINOIC ACID; CELL-LINES; PROTOONCOGENE EXPRESSION; EWINGS-SARCOMA; GROWTH-FACTOR; N-MYC; DIFFERENTIATION; NEUROEPITHELIOMA AB The pediatric peripheral neuroectodermal tumors which include neuroblastoma, peripheral neuroepithelioma and Ewing's sarcoma may correspond to distinct neural crest cell lineages or tumors arrested at different stages of neural crest development. Besides a brief commentary on the salient clinical features of these tumors, this review examines how cell and molecular biological studies have contributed to a re-classification of these tumors. The differentiation of these tumors is reviewed with a particular emphasis on retinoic acid induced differentiation of neuroblastoma as a model to identify genes important in controlling cell growth, suppression of tumorigenicity and induction of differentiation. RP THIELE, CJ (reprint author), NCI,PEDIAT BRANCH,MOLEC GENET SECT,BETHESDA,MD 20892, USA. NR 41 TC 46 Z9 46 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-7659 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD DEC PY 1991 VL 10 IS 4 BP 311 EP 319 DI 10.1007/BF00554793 PG 9 WC Oncology SC Oncology GA HF670 UT WOS:A1991HF67000005 PM 1786632 ER PT J AU SPORN, MB AF SPORN, MB TI CARCINOGENESIS AND CANCER - DIFFERENT PERSPECTIVES ON THE SAME DISEASE SO CANCER RESEARCH LA English DT Article ID RETINOIC ACID; BREAST-CANCER; PREVENTION; TAMOXIFEN; ISOTRETINOIN; CARCINOMA; RECEPTOR; TUMORS; MODEL; RATS RP SPORN, MB (reprint author), NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892, USA. NR 38 TC 131 Z9 135 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 1991 VL 51 IS 23 BP 6215 EP 6218 PG 4 WC Oncology SC Oncology GA GR475 UT WOS:A1991GR47500001 PM 1933881 ER PT J AU PEPE, S TORTORA, G NOGUCHI, PD MARTI, GE WASHINGTON, GC CHOCHUNG, YS AF PEPE, S TORTORA, G NOGUCHI, PD MARTI, GE WASHINGTON, GC CHOCHUNG, YS TI EFFECTS OF 8-CHLOROADENOSINE 3',5'-MONOPHOSPHATE AND N6-BENZYL-CYCLIC ADENOSINE 5'-MONOPHOSPHATE ON CELL-CYCLE KINETICS OF HL-60 LEUKEMIA-CELLS SO CANCER RESEARCH LA English DT Article ID DEPENDENT PROTEIN-KINASES; SELECTIVE CAMP ANALOGS; AMINO-ACID SEQUENCE; GROWTH-CONTROL; BINDING-SITES; AMP ANALOGS; REGULATORY SUBUNIT; ESTROGEN-RECEPTOR; GENE-EXPRESSION; DIFFERENTIATION AB Site-selective cyclic AMP (cAMP) analogues have been shown to inhibit growth and induce differentiation in several human leukemia cell lines. However, detailed studies of the effects exerted by cAMP analogues on cell cycle kinetics have been lacking. We have examined the effects of 8-Cl-cAMP and N6-benzyl-cAMP on the cell cycle kinetics of the HL-60 human promyelocytic leukemia cell line. A cell cycle study was performed by univariate DNA analysis after 24-72 h of treatment with noncytotoxic concentrations of 8-Cl-cAMP and N6-benzyl-cAMP capable of inducing 50-60% growth inhibition in these cells. HL-60 cells treated with 5-mu-m 8-Cl-cAMP showed no significant change in the cell distribution in the cycle as compared to the untreated control cells, whereas the treatment with 10-mu-M N6-benzyl-cAMP transiently increased the percentage of cells in the G0/G1 phase after 48 h, followed by a partial recovery at 72 h. Combined treatment with low doses of 8-Cl-cAMP and N6-benzyl-cAMP, each of which alone produced 20% growth inhibition, exerted a growth inhibitory effect of 65% and delayed increase of the G0/G1 phase by 72 h. To better understand the cell cycle effects induced by 8-Cl-cAMP, flow cytometric analysis of bromodeoxyuridine incorporation was also performed. 8-Cl-cAMP treatment exhibited a slowing down of the cell cycle; thus, the delayed appearance of the G0/G1 cell accumulation after combined treatment could be due to this effect of 8-Cl-cAMP on the HL-60 cell cycle. At a toxic dose, 8-Cl-cAMP brought about a G2M block, whereas N6-benzl-cAMP brought about an increase of the G0/G1 compartment. G2M block produced by toxic doses of 8-Cl-cAMP was not related to its adenosine metabolite since 8-Cl-adenosine did not produce any specific block in the cell cycle. Our results show, for the first time, that these site-selective cAMP analogues could affect cell cycle kinetics at different points. These data may provide the basis for combination treatments involving cAMP analogues and other agents in the treatment of human leukemia. C1 NCI,CELLULAR BIOCHEM SECT,TUMOR IMMUNOL & BIOL LAB,BLDG 10,ROOM 5B38,BETHESDA,MD 20892. US FDA,CTR BIOL RES & EVALUAT,DIV BIOCHEM & BIOPHYS,BETHESDA,MD 20014. NR 27 TC 19 Z9 19 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 1991 VL 51 IS 23 BP 6263 EP 6267 PG 5 WC Oncology SC Oncology GA GR475 UT WOS:A1991GR47500009 PM 1657383 ER PT J AU BERTRAND, R SARANG, M JENKIN, J KERRIGAN, D POMMIER, Y AF BERTRAND, R SARANG, M JENKIN, J KERRIGAN, D POMMIER, Y TI DIFFERENTIAL INDUCTION OF SECONDARY DNA FRAGMENTATION BY TOPOISOMERASE-II INHIBITORS IN HUMAN TUMOR-CELL LINES WITH AMPLIFIED C-MYC EXPRESSION SO CANCER RESEARCH LA English DT Article ID MOUSE LEUKEMIA-L1210 CELLS; CHINESE-HAMSTER CELLS; CYTO-TOXICITY; STRAND BREAKS; DEATH; ETOPOSIDE; ACTIVATION; APOPTOSIS; CLEAVAGE; 4'-(9-ACRIDINYLAMINO)METHANESULFON-META-ANISIDIDE AB In order to understand the cellular events associated with cell death after the formation of topoisomerase II-DNA cleavable complexes, we compared the induction of endonucleolytic DNA fragmentation by etoposide and its more potent analog, teniposide (VM-26) in the human cell lines HT-29 and HL-60. A new filter-binding assay is described, which allows rapid quantification of nonprotein-linked DNA fragmentation involved in apoptosis. Both cell lines showed similar loss of colony formation ability following 30 min of treatment with various VM-26 concentrations even though the initial topoisomerase II-mediated DNA single-strand break frequency was higher in HL-60 cells. DNA repair studies following drug removal indicated that VM-26-induced DNA breaks reversed rapidly and completely in HT-29 cells, while in HL-60 cells, the initial lesions persisted at and above 5-mu-M VM-26. In both cell lines, topoisomerase II cleavage complexes, as measured by DNA-protein cross-links by alkaline elution, reversed rapidly and completely within 2-3 h. Secondary DNA fragmentation resembling chromatin endonucleolytic cleavage by apoptosis could be detected in HL-60 cells 3 h after VM-26 or etoposide treatment but not in HT-29 cells. Secondary DNA fragmentation was also induced in the human colon cancer cell lines COLO 320, which have c-myc amplification. Since HL-60 cells also have c-myc amplification and HT-29 do not, it is possible that c-myc over-expression may be involved in secondary DNA fragmentation. Finally, our results indicate heterogeneity of cell death mechanisms after exposure to topoisomerase II inhibitors among human cancer cell lines. C1 NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NR 41 TC 177 Z9 178 U1 2 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 1991 VL 51 IS 23 BP 6280 EP 6285 PG 6 WC Oncology SC Oncology GA GR475 UT WOS:A1991GR47500012 PM 1933888 ER PT J AU MILENIC, DE YOKOTA, T FILPULA, DR FINKELMAN, MAJ DODD, SW WOOD, JF WHITLOW, M SNOY, P SCHLOM, J AF MILENIC, DE YOKOTA, T FILPULA, DR FINKELMAN, MAJ DODD, SW WOOD, JF WHITLOW, M SNOY, P SCHLOM, J TI CONSTRUCTION, BINDING-PROPERTIES, METABOLISM, AND TUMOR TARGETING OF A SINGLE-CHAIN FV DERIVED FROM THE PANCARCINOMA MONOCLONAL-ANTIBODY CC49 SO CANCER RESEARCH LA English DT Article ID GLYCOPROTEIN TAG-72; ESCHERICHIA-COLI; B72.3; ANTIGEN; CARCINOMA; PROTEINS; CANCER; RADIOLOCALIZATION; ESTABLISHMENT; IMMUNOTOXIN AB CC49 is a "second generation" monoclonal antibody to B72.3, which reacts with the pancarcinoma antigen TAG-72. CC49 has been shown to efficiently target human colon carcinoma xenografts and is currently being evaluated in both diagnostic and therapeutic clinical trials. We describe here the construction and characterization of a recombinant single-chain Fv (sFv) of CC49. The sFv was shown to be a M(r) 27,000 homogeneous entity which could be efficiently radiolabeled with I-125 or I-131. Comparative direct binding studies and competition radioimmunoassays using CC49 intact IgG, F(ab')2, Fab', and sFv revealed that the monomeric CC49 Fab' and sFv had relative binding affinities 8-fold lower than the dimeric F(ab')2 and intact IgG. Nonetheless, the I-131-labeled sFv was shown to bind biopsies of TAG-72-expressing tumors. Metabolism studies in mice, using radiolabeled CC49 IgG, F(ab')2, Fab', and sFv, demonstrated an extremely rapid plasma and whole body clearance for the sFv. CC49 sFv plasma pharmacokinetic studies in rhesus monkeys also showed a very rapid plasma clearance (T1/2-alpha of 3.9 min and T1/2-beta of 4.2 h). Tumor targeting studies with all four radiolabeled Ig CC49 forms, using the LS-174T human colon carcinoma xenograft model, revealed a much lower percentage injected dose/g tumor binding for the CC49 monomeric sFv and Fab' as compared to the dimeric F(ab')2 and intact IgG. However, tumor:normal tissue ratios (radiolocalization indices) for the sFv were comparable to or greater than those of the other Ig forms. High kidney uptake with I-125-labeled Fab' and F(ab')2 was not seen with I-125-sFv. Gamma scanning studies also showed that I-131-CC49 sFv could efficiently localize tumors. The CC49 sFv may thus have utility in diagnostic and perhaps therapeutic applications for a range of human carcinomas. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BLDG 10,ROOM 8B07,BETHESDA,MD 20892. GENEX CORP,GAITHERSBURG,MD 20877. US BUR BIOL,BETHESDA,MD 20892. NR 33 TC 347 Z9 356 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 1991 VL 51 IS 23 BP 6363 EP 6371 PG 9 WC Oncology SC Oncology GA GR475 UT WOS:A1991GR47500025 PM 1933899 ER PT J AU SWENBERG, JA HOEL, DG MAGEE, PN AF SWENBERG, JA HOEL, DG MAGEE, PN TI MECHANISTIC AND STATISTICAL INSIGHT INTO THE LARGE CARCINOGENESIS BIOASSAYS ON N-NITROSODIETHYLAMINE AND N-NITROSODIMETHYLAMINE SO CANCER RESEARCH LA English DT Article ID DOSE-RESPONSE; RAT-LIVER; DIETHYLNITROSAMINE; DIMETHYLNITROSAMINE; DNA; O-4-ETHYLDEOXYTHYMIDINE; ACCUMULATION; PERSISTENCE; TOXICOLOGY; INITIATION C1 NIEHS,RES TRIANGLE PK,NC 27709. RP SWENBERG, JA (reprint author), UNIV N CAROLINA,DEPT ENVIRONM SCI & ENGN,CHAPEL HILL,NC 27599, USA. NR 40 TC 54 Z9 54 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 1991 VL 51 IS 23 SU S BP 6409 EP 6414 PG 6 WC Oncology SC Oncology GA GU409 UT WOS:A1991GU40900001 PM 1933905 ER PT J AU FORKERT, PG MASSEY, TE JONES, AB PARK, SS GELBOIN, HV ANDERSON, LM AF FORKERT, PG MASSEY, TE JONES, AB PARK, SS GELBOIN, HV ANDERSON, LM TI DISTRIBUTION OF CYTOCHROME-CYP2E1 IN MURINE LIVER AFTER ETHANOL AND ACETONE ADMINISTRATION SO CARCINOGENESIS LA English DT Article ID N-NITROSODIMETHYLAMINE DEMETHYLASE; MICROSOMAL DIMETHYLNITROSAMINE DEMETHYLASE; MONOCLONAL-ANTIBODIES; IMMUNOCHEMICAL EVIDENCE; RAT-LIVER; IMMUNOHISTOCHEMICAL LOCALIZATION; INDUCIBLE CYTOCHROME-P-450; INDUCTION; PYRAZOLE; MICE AB The effects of acetone and ethanol administration on cytochrome CYP2E1 in murine liver were investigated. A monoclonal antibody (Mab 1-98-1) specific to rat ethanol-inducible P450 recognized a major band of M(r) 51 000 in Western immunoblots of mouse liver microsomes. This band was increased 1.8-fold by 10% ethanol in drinking water for 2 weeks, 4.7-fold by 1% acetone in drinking water for 1 week, and 2.5-, 2.1- and 6.8-fold by ethanol in a liquid diet for 9 days, 2 weeks and 3 weeks respectively. Immunohistochemical staining experiments with the same antibody showed specific localization in centrilobular regions of liver lobules, with variations in intensity that corresponded to differences detected in Western immunoblots. Uniform cellular increases in centrilobular staining occurred with all ethanol treatments, whereas a more heterogeneous increase in individual cells was noted after acetone. Lipid accumulation in hepatocytes was pronounced after 3 weeks on the ethanol lipid diet but was less so in other treatment groups, and thus did not consistently correlate with enzyme induction. Microsomal aniline p-hydroxylase activity was also induced by the acetone and ethanol treatments, with a progressive increase from 9 days to 3 weeks on the ethanol liquid diet. Changes in this activity in general paralleled those found with immunohistochemistry and immunoblotting. The results demonstrate that (i) the mouse is a good model for correlative biochemical and histochemical studies of CYP2E1 induction, (ii) in the mouse liver, this P450 is preferentially localized in centrilobular regions constitutively as well as in induced states, (iii) the centrilobular pattern varies under different induction conditions, and (iv) there is a progressive inductive increase in CYP2E1 protein and enzyme activity with chronic ethanol treatment over at least 3 weeks. C1 QUEENS UNIV,DEPT MED,KINGSTON K7L 3N6,ONTARIO,CANADA. QUEENS UNIV,DEPT PHARMACOL & TOXICOL,KINGSTON K7L 3N6,ONTARIO,CANADA. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES FACIL,DIV CANC ETIOL,COMPARAT CARCINOGENESIS,FREDERICK,MD 21701. RP FORKERT, PG (reprint author), QUEENS UNIV,DEPT ANAT,KINGSTON K7L 3N6,ONTARIO,CANADA. NR 46 TC 42 Z9 42 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 DEC PY 1991 VL 12 IS 12 BP 2259 EP 2268 DI 10.1093/carcin/12.12.2259 PG 10 WC Oncology SC Oncology GA GV518 UT WOS:A1991GV51800011 PM 1747925 ER PT J AU LIU, YH TAYLOR, J LINKO, P LUCIER, GW THOMPSON, CL AF LIU, YH TAYLOR, J LINKO, P LUCIER, GW THOMPSON, CL TI GLUTATHIONE S-TRANSFERASE-MU IN HUMAN LYMPHOCYTE AND LIVER - ROLE IN MODULATING FORMATION OF CARCINOGEN-DERIVED DNA ADDUCTS SO CARCINOGENESIS LA English DT Article ID TRANS-STILBENE OXIDE; HUMAN MONONUCLEAR LEUKOCYTES; METABOLIC-ACTIVATION; GENE DELETION; LUNG-CANCER; AFLATOXIN-B1; BINDING; RAT; CYTOCHROME-P-450; BENZOPYRENE AB Glutathione transferase (GT) activity towards trans-stilbene oxide (tSBO), benzo[a]pyrene-4,5-oxide (B[a]PO) and 1-chloro-2,4-dinitrobenzene (CDNB) was measured in human liver and lymphocytes. GT-tSBO activity is catalyzed by GT-mu which has polymorphic expression in human lymphocytes. Our results show that activity of GT-tSBO in lymphocytes correlates with its activity in liver (r = 0.7, P < 0.001). GT activity towards BPO (GT-BPO) also correlated with GT-tSBO in lymphocytes and liver. However, interindividual variation of GT-BPO is less than that of GT-tSBO, suggesting that BPO may not be as specific a substrate for GT-mu and therefore other GT isozymes may contribute to BPO conjugation. Conjugation of CDNB by GT was not different using cytosols from either high or low GT-mu individuals. The functional significance of the GT-mu polymorphism was evaluated by measuring its effect on benzo[a]pyrene (B[a]P)- and aflatoxin B1 (AFB1)-DNA adduct formation in vitro. Human liver cytosols prepared from persons having low or high GT-tSBO activity were incubated with human liver microsomes, calf thymus DNA and B[a]P or AFB1. HPLC analysis revealed that the major B[a]P adduct was dG(N2)-7-beta, 8-alpha-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE-dG). BPDE-dG adducts were decreased equally by cytosols from either low or high conjugators. In contrast, AFB1-DNA binding was inhibited to a greater extent in high conjugators than low conjugators. HPLC analysis demonstrates that adducts formed were AFB1-FAPyr and AFB1-N7-Gua. The correlation between AFB1-DNA adduct concentrations and GT-mu activity was highly significant with a correlation coefficient of r = 0.88 at P < 0.001. These results suggest that GT-mu plays an important role in detoxifying DNA reactive metabolites of AFB1 and this enzyme may be a susceptibility marker for AFB1 related liver cancer. Moreover, our data demonstrate that lymphocytes are a reliable surrogate tissue for detecting liver GT-mu polymorphisms. C1 NIEHS,BIOCHEM RISK ANAL LAB,RES TRIANGLE PK,NC 27709. NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. RP THOMPSON, CL (reprint author), NIEHS,BIOCHEM RISK ANAL LAB,RES TRIANGLE PK,NC 27709, USA. OI taylor, jack/0000-0001-5303-6398 NR 47 TC 71 Z9 73 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 DEC PY 1991 VL 12 IS 12 BP 2269 EP 2275 DI 10.1093/carcin/12.12.2269 PG 7 WC Oncology SC Oncology GA GV518 UT WOS:A1991GV51800012 PM 1747926 ER PT J AU DOLAN, ME PEGG, AE DUMENCO, LL MOSCHEL, RC GERSON, SL AF DOLAN, ME PEGG, AE DUMENCO, LL MOSCHEL, RC GERSON, SL TI COMPARISON OF THE INACTIVATION OF MAMMALIAN AND BACTERIAL O6-ALKYLGUANINE-DNA ALKYLTRANSFERASES BY O6-BENZYLGUANINE AND O6-METHYLGUANINE SO CARCINOGENESIS LA English DT Article ID HUMAN O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; HUMAN-LEUKEMIC CELLS; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; ESCHERICHIA-COLI; ALKYLATING-AGENTS; RAT-LIVER; DNA METHYLTRANSFERASE; TUMOR-CELLS; ADA GENE; REPAIR AB The inactivation of human and Escherichia coli O6-alkylguanine-DNA alkyltransferase by O6-methylguanine and O6-benzylguanine was compared. When HT29 cell extracts or E.coli Ada protein were incubated in the presence of 200-mu-M O6-methylguanine for 1 h, alkyltransferase activity was reduced to 44 and 39% of control levels respectively. However, under the same conditions O6-benzylguanine completely depleted alkyltransferase activity in the extract from human cells but had virtually no effect on the Ada protein. Incubation of the HT29 cell alkyltransferase with O6-benzyl[H-3]guanine resulted in a time-dependent production of [H-3]guanine. No similar production of [H-3]guanine was observed in the presence of the Ada protein. In CHO cells transfected with the bacterial ada gene (CHO-ada) or the human alkyltransferase cDNA (CHO-MGMT), treatment with 500-mu-M O6-methylguanine inhibited both alkyltransferases by > 85%. In contrast, 2-mu-M O6-benzylguanine inhibited human alkyltransferase expressed in CHO-MGMT cells by > 99% though concentrations as high as 25-mu-M for 24 h had no inhibitory effects on the bacterial alkyltransferase expressed in CHO-ada cells. This selective inhibition was also observed in vivo in transgenic mice expressing ada in the liver where O6-benzylguanine caused a decrease of only 40% in total hepatic alkyltransferase activity compared to 95% in non-transgenic mice, consistent with inhibition of only the mammalian alkyltransferase and maintenance of bacterial alkyltransferase activity in these animals. Thus, while O6-methylguanine at high concentrations inactivates both bacterial and mammalian alkyltransferases, O6-benzylguanine is a substrate only for the mammalian protein and is unable, perhaps due to steric hindrance, to inhibit the Ada protein. C1 PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT CELLULAR & MOLEC PHYSIOL,HERSHEY,PA 17033. PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT PHARMACOL,HERSHEY,PA 17033. UNIV HOSP CLEVELAND,DIV HEMATOL ONCOL,CLEVELAND,OH 44106. UNIV HOSP CLEVELAND,RL IRELAND CANC CTR,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,SCH MED,CLEVELAND,OH 44106. NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,FREDERICK,MD 21701. RP DOLAN, ME (reprint author), UNIV CHICAGO,MED CTR,DIV HEMATOL ONCOL,5841 S MARYLAND AVE,BOX 420,CHICAGO,IL 60637, USA. FU NCI NIH HHS [P01 CA-51183, CA-47228, CA-45609] NR 42 TC 75 Z9 76 U1 2 U2 3 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 DEC PY 1991 VL 12 IS 12 BP 2305 EP 2309 DI 10.1093/carcin/12.12.2305 PG 5 WC Oncology SC Oncology GA GV518 UT WOS:A1991GV51800018 PM 1747932 ER PT J AU THOMPSON, PA LEDBETTER, JA RAPP, UR BOLEN, JB AF THOMPSON, PA LEDBETTER, JA RAPP, UR BOLEN, JB TI THE RAF-1 SERINE-THREONINE KINASE IS A SUBSTRATE FOR THE P56LCK PROTEIN TYROSINE KINASE IN HUMAN T-CELLS SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID PHOSPHOLIPASE-C-GAMMA; PDGF BETA-RECEPTOR; SIGNAL TRANSDUCTION; CD4 RECEPTOR; LYMPHOCYTES-T; PHOSPHORYLATION; ACTIVATION; ASSOCIATION; EXPRESSION; MEMBRANE AB The CD4 receptor subserves both adhesion and signal transduction functions on CD4+ T-lymphocytes. CD4 is physically associated with the src-related protein tyrosine kinase p56lck. Cell surface engagement of CD4 leads to enzymatic activation of the associated p56lck and the phosphorylation of T-cell proteins on tyrosine residues. We have identified a 72-74kD protein phosphorylated on tyrosine residues following activation of CD4-associated p56lck as the serine-threonine kinase Raf-1. The demonstration that Raf-1 is a substrate for the CD4/p56lck receptor system in normal cells suggests that receptor and nonreceptor classes of protein tyrosine kinases can independently engage functionally overlapping signal transduction pathways. C1 BRISTOL MYERS SQUIBB PHARMACEUT RES INST,DEPT MOLEC BIOL,ROOM H-4427B,POB 4000,PRINCETON,NJ 08543. NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,SEATTLE,WA 98121. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. NR 47 TC 48 Z9 48 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD DEC PY 1991 VL 2 IS 12 BP 609 EP 617 PG 9 WC Cell Biology SC Cell Biology GA GV599 UT WOS:A1991GV59900001 PM 1687313 ER PT J AU SMYTH, MJ NORIHISA, Y GERARD, JR YOUNG, HA ORTALDO, JR AF SMYTH, MJ NORIHISA, Y GERARD, JR YOUNG, HA ORTALDO, JR TI IL-7 REGULATION OF CYTOTOXIC LYMPHOCYTES - PORE-FORMING PROTEIN GENE-EXPRESSION, INTERFERON-GAMMA PRODUCTION, AND CYTOTOXICITY OF HUMAN PERIPHERAL-BLOOD LYMPHOCYTE SUBSETS SO CELLULAR IMMUNOLOGY LA English DT Article ID NATURAL-KILLER CELLS; LARGE GRANULAR LYMPHOCYTES; T-CELLS; GROWTH-FACTOR; INTERLEUKIN-2 RECEPTOR; MOLECULAR-CLONING; IFN-GAMMA; PROLIFERATION; DIFFERENTIATION; ACTIVATION RP SMYTH, MJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702, USA. RI Smyth, Mark/H-8709-2014 OI Smyth, Mark/0000-0001-7098-7240 NR 41 TC 57 Z9 57 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD DEC PY 1991 VL 138 IS 2 BP 390 EP 403 DI 10.1016/0008-8749(91)90163-6 PG 14 WC Cell Biology; Immunology SC Cell Biology; Immunology GA GP549 UT WOS:A1991GP54900012 PM 1834347 ER PT J AU RAPOPORT, SI AF RAPOPORT, SI TI POSITRON EMISSION TOMOGRAPHY IN ALZHEIMERS-DISEASE IN RELATION TO DISEASE PATHOGENESIS - A CRITICAL-REVIEW SO CEREBROVASCULAR AND BRAIN METABOLISM REVIEWS LA English DT Review DE ALZHEIMERS DISEASE; POSITRON EMISSION TOMOGRAPHY; GLUCOSE; BLOOD FLOW; STIMULATION; COGNITION; NEUROPSYCHOLOGY; METABOLISM; BLOOD BRAIN BARRIER; SYNAPSES; ANATOMY; ASSOCIATION NEOCORTICES; NEURODEGENERATION; IMAGING; DEMENTIA; NEUROPATHOLOGY; FLUORODEOXYGLUCOSE ID CEREBRAL BLOOD-FLOW; GLUCOSE METABOLIC RATES; AUDITORY BRAIN-STEM; SENILE DEMENTIA; DOWNS-SYNDROME; PATHOLOGICAL-CHANGES; PRESENILE-DEMENTIA; DEVELOPMENTAL-CHANGES; OXIDATIVE-METABOLISM; COMPUTED-TOMOGRAPHY AB PET studies of brain metabolism and blood flow in Alzheimer's disease (AD) patients lead to the following conclusions: (a) Reductions in "resting state" regional brain metabolism are roughly proportional to dementia severity. (b) These reductions are greater in association than in primary sensory and motor neocortical regions, and correlate with the distribution of neuropathology and cell loss postmortem. (c) Demented but not nondemented Down syndrome adults also have worse metabolic reductions in the association than primary neocortices, suggesting an equivalent pathological process in demented Down syndrome and AD patients. (d) Brain metabolic patterns in AD patients are heterogeneous, belonging to at least four distinct metabolic groups that correspond to different patterns of cognitive and behavioral abnormalities; the metabolic patterns have not been shown to be related to disease etiology. (e) Abnormal right-left metabolic asymmetries in mildly demented AD patients can retain their initial directions for as long as 48 months; these asymmetries precede and predict the cognitive "discrepancies" that later appear, such that moderately demented patients with disproportionate visuospatial compared with language deficits, or disproportionate visual recall compared with verbal recall, have a greater metabolic reduction in the right than left hemisphere, and vice versa. (f) Parietal association/frontal association metabolic ratios also retain their direction over time; in moderately demented patients, relative hypometabolism in the prefrontal association cortex is related to deficits in verbal fluency and attention to simple sets, whereas relative hypometabolism in the parietal association cortex correlates with failure in arithmetic, verbal comprehension, drawing, and immediate memory for visuospatial location. (g) Although metabolically spared compared with the association cortices, the primary sensory cortices, basal ganglia, thalamus, and cerebellar hemispheres show metabolic declines in AD using high-resolution PET scanners, possibly due to their connections with more pathologically affected regions. (h) Early metabolic deficits in AD are hypothesized to arise from synaptic failure in association cortical areas; such failure in the occipitotemporal visual cortex can be reversed in mildly to moderately demented AD patients who are capable of performing a face-matching task. RP RAPOPORT, SI (reprint author), NIA,NEUROSCI LAB,BLDG 10,ROOM 6C103,BETHESDA,MD 20892, USA. NR 213 TC 131 Z9 134 U1 5 U2 10 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1040-8827 J9 CEREBROVAS BRAIN MET JI Cerebrovasc. Brain Metab. Rev. PD WIN PY 1991 VL 3 IS 4 BP 297 EP 335 PG 39 WC Neurosciences SC Neurosciences & Neurology GA GR410 UT WOS:A1991GR41000002 PM 1772739 ER PT J AU Wu, XG Chee, MN Kapral, R AF Wu, Xiao-Guang Chee, Merk-Na Kapral, Raymond TI Vortex dynamics in oscillatory chemical systems SO CHAOS LA English DT Article AB Vortex core dynamics is studied in the Brusselator both near to and far from the Hopf bifurcation line for random and pair initial conditions. Extensive simulations are carried out for a pair of counter-rotating vortices close to the Hopf bifurcation line. Provided the vortices are not so far apart that wave-front annihilation produces strong gradients between their centers, the simulation results compare favorably with theories based on the complex Ginzburg-Landau equation. Far from the Hopf line the vortex core dynamics changes character and phenomena such as periodic motion of the vortex centers arise. C1 [Wu, Xiao-Guang; Kapral, Raymond] Univ Toronto, Dept Chem, Chem Phys Theory Grp, Toronto, ON M5S 1A1, Canada. [Chee, Merk-Na] NEI, NIH, Bethesda, MD 20892 USA. RP Wu, XG (reprint author), Univ Toronto, Dept Chem, Chem Phys Theory Grp, 100 Coll St, Toronto, ON M5S 1A1, Canada. FU Natural Sciences and Engineering Research Council of Canada; Institute for Scientific Interchange Foundation, Torino, Italy FX This work was supported in part by a grant from the Natural Sciences and Engineering Research Council of Canada. Part of this work was done while R.K. was at the Institute for Scientific Interchange Foundation, Torino, Italy and he would like to thank the members of this Foundation for their hospitality and support. NR 40 TC 4 Z9 4 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA SN 1054-1500 EI 1089-7682 J9 CHAOS JI Chaos PD DEC PY 1991 VL 1 IS 4 DI 10.1063/1.165852 PG 14 WC Mathematics, Applied; Physics, Mathematical SC Mathematics; Physics GA V22XM UT WOS:000208307900005 ER PT J AU KNAUS, WA WAGNER, DP DRAPER, EA ZIMMERMAN, JE BERGNER, M BASTOS, PG SIRIO, CA MURPHY, DJ LOTRING, T DAMIANO, A HARRELL, FE AF KNAUS, WA WAGNER, DP DRAPER, EA ZIMMERMAN, JE BERGNER, M BASTOS, PG SIRIO, CA MURPHY, DJ LOTRING, T DAMIANO, A HARRELL, FE TI THE APACHE-III PROGNOSTIC SYSTEM - RISK PREDICTION OF HOSPITAL MORTALITY FOR CRITICALLY ILL HOSPITALIZED ADULTS SO CHEST LA English DT Article ID INTENSIVE-CARE UNIT; ACUTE MYOCARDIAL-INFARCTION; OUTCOME PREDICTION; ORGAN FAILURE; SCORE; DECISIONS; SURVIVAL; MODELS; TRIAL AB The objective of this study was to refine the APACHE (Acute Physiology, Age, Chronic Health Evaluation) methodology in order to more accurately predict hospital mortality risk for critically ill hospitalized adults. We prospectively collected data on 17,440 unselected adult medical/surgical intensive care unit (ICU) admissions at 40 US hospitals (14 volunteer tertiary-care institutions and 26 hospitals randomly chosen to represent intensive care services nationwide). We analyzed the relationship between the patient's likelihood of surviving to hospital discharge and the following predictive variables: major medical and surgical disease categories, acute physiologic abnormalities, age, preexisting functional limitations, major comorbidities, and treatment location immediately prior to ICU admission. The APACHE III prognostic system consists of two options: (1) an APACHE III score, which can provide initial risk stratification for severely ill hospitalized patients within independently defined patient groups; and (2) an APACHE III predictive equation, which uses APACHE III score and reference data on major disease categories and treatment location immediately prior to ICU admission to provide risk estimates for hospital mortality for individual ICU patients. A five-point increase in APACHE III score (range, 0 to 299) is independently associated with a statistically significant increase in the relative risk of hospital death (odds ratio, 1.10 to 1.78) within each of 78 major medical and surgical disease categories. The overall predictive accuracy of the first-day APACHE III equation was such that, within 24 h of ICU admission, 95 percent of ICU admissions could be given a risk estimate for hospital death that was within 3 percent of that actually observed (r2 = 0.41; receiver operating characteristic = 0.90). Recording changes in the APACHE III score on each subsequent day of ICU therapy provided daily updates in these risk estimates. When applied across the individual ICUs, the first-day APACHE III equation accounted for the majority of variation in observed death rates (r2 = 0.90, p < 0.0001). C1 GEORGE WASHINGTON UNIV, MED CTR,DEPT ANESTHESIOL,INTENS CARE UNIT,RES UNIT, WASHINGTON, DC 20037 USA. APACHE MED SYST INC, BALTIMORE, MD USA. JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, CTR HLTH SERV RES & DEV, BALTIMORE, MD 21218 USA. NIH, DEPT CRIT CARE MED, BETHESDA, MD 20892 USA. DUKE UNIV, MED CTR, DIV BIOMETRY, DURHAM, NC 27710 USA. RP KNAUS, WA (reprint author), 2300 K ST NW, WASHINGTON, DC 20037 USA. FU AHRQ HHS [HS05787] NR 45 TC 2190 Z9 2305 U1 5 U2 34 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD DEC PY 1991 VL 100 IS 6 BP 1619 EP 1636 DI 10.1378/chest.100.6.1619 PG 18 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA GU051 UT WOS:A1991GU05100030 PM 1959406 ER PT J AU KOCHANSKA, G AF KOCHANSKA, G TI SOCIALIZATION AND TEMPERAMENT IN THE DEVELOPMENT OF GUILT AND CONSCIENCE SO CHILD DEVELOPMENT LA English DT Article ID CHILDREN; PERSPECTIVE; PSYCHOPATHOLOGY; NONCOMPLIANCE; BEHAVIOR; EMPATHY; MOTHERS; BOYS; AGE AB Toddlerhood antecedents of conscience were examined in 58 8-10-year-old children. The measures of conscience, such as general affective/moral orientation, the extent of reparation, and the intensity of guilt feelings, were assessed from children's narratives produced in response to semiprojective stories involving transgressions, distress, and conflict. Maternal endorsed socialization orientations and observed rearing behaviors that deemphasized the use of power were associated with the children's internalized conscience 6 years later. However, these findings were significant only for children who were relatively prone to fearful arousal. The capacity for self-regulation, indexed by early compliance and noncompliance to maternal socialization, predicted children's internalized conscience 6 years later. There was preliminary evidence that compliance obtained in a rearing context that deemphasized power assertion was most conducive to the development of conscience. The findings are discussed in view of the interplay of socialization and temperament in moral development. C1 NIMH,BETHESDA,MD 20892. NR 60 TC 180 Z9 182 U1 1 U2 29 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0009-3920 J9 CHILD DEV JI Child Dev. PD DEC PY 1991 VL 62 IS 6 BP 1379 EP 1382 DI 10.1111/j.1467-8624.1991.tb01612.x PG 4 WC Psychology, Educational; Psychology, Developmental SC Psychology GA GX300 UT WOS:A1991GX30000012 PM 1786722 ER PT J AU JOURILES, EN MURPHY, CM FARRIS, AM SMITH, DA RICHTERS, JE WATERS, E AF JOURILES, EN MURPHY, CM FARRIS, AM SMITH, DA RICHTERS, JE WATERS, E TI MARITAL ADJUSTMENT, PARENTAL DISAGREEMENTS ABOUT CHILD-REARING, AND BEHAVIOR PROBLEMS IN BOYS - INCREASING THE SPECIFICITY OF THE MARITAL ASSESSMENT SO CHILD DEVELOPMENT LA English DT Article ID CONFLICT; DISCORD; QUALITY; ANGER AB 2 studies were conducted to illustrate how measuring a specific aspect of marriage, namely, child-rearing disagreements, provides a better understanding of the link between marriage and boys' behavior. In Study 1, 200 mothers of 3-year-old boys completed unstandardized measures of marital functioning and child behavior. An index of child-rearing disagreements: (1) correlated with a greater variety of behavior problems than nonchild disagreements, and (2) improved upon the prediction of behavior problems after accounting for nonchild disagreements as well as after accounting for boys' exposure to marital conflict. In Study 2, 87 mothers with 4-6-year-old sons completed the index of child-rearing disagreements used in Study 1 as well as standard measures of marital functioning and child behavior. Child-rearing disagreements: (1) predicted a greater variety of behavior problems than global marital adjustment, and (2) improved upon the prediction of internalizing problems after controlling for global marital adjustment as well as after controlling for boys' exposure to marital conflict. C1 SUNY STONY BROOK,STONY BROOK,NY 11794. NIMH,BETHESDA,MD 20892. RP JOURILES, EN (reprint author), UNIV HOUSTON,DEPT PSYCHOL,4800 CALHOUN RD,HOUSTON,TX 77204, USA. OI Richters, John/0000-0002-6780-1828 FU NIMH NIH HHS [MH35340] NR 22 TC 130 Z9 131 U1 1 U2 7 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0009-3920 J9 CHILD DEV JI Child Dev. PD DEC PY 1991 VL 62 IS 6 BP 1424 EP 1433 DI 10.2307/1130816 PG 10 WC Psychology, Educational; Psychology, Developmental SC Psychology GA GX300 UT WOS:A1991GX30000015 PM 1786725 ER PT J AU KOCHANSKA, G KUCZYNSKI, L AF KOCHANSKA, G KUCZYNSKI, L TI MATERNAL AUTONOMY GRANTING - PREDICTORS OF NORMAL AND DEPRESSED MOTHERS COMPLIANCE AND NONCOMPLIANCE WITH THE REQUESTS OF 5-YEAR-OLDS SO CHILD DEVELOPMENT LA English DT Article ID CHILD COMPLIANCE; YOUNG-CHILDREN; MOOD; STRATEGIES; PATTERNS; BEHAVIOR; RESPONSIVENESS; SOCIALIZATION; OBEDIENCE; PARENTS AB Maternal compliance and noncompliance to child requests, thought to represent an autonomy-granting aspect of socialization, were studied in 24 well mothers and 26 mothers with a history of depression and their 5-year-old children. Mothers continued to retain substantially more power than children in the control process. There were no differences between normal and depressed mothers in the extent to which they granted or denied their children's requests, but the determinants of maternal autonomy granting differed in the 2 groups. Depressed, but not well, mothers' responses to child requests could be predicted from their self-reported mood prior to the interaction and from the concurrent child's behavior. Depressed mothers who reported negative mood and whose children were uncooperative most often denied their requests. Depressed mothers' noncompliance to their children's requests was determined by the quantity rather than quality of their children's behavior: they did not discriminate between skillful and unskillful forms of the children's autonomy expressions. C1 NIMH,BETHESDA,MD 20892. UNIV GUELPH,DEPT FAMILY STUDIES,GUELPH N1G 2W1,ONTARIO,CANADA. NR 44 TC 15 Z9 15 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0009-3920 J9 CHILD DEV JI Child Dev. PD DEC PY 1991 VL 62 IS 6 BP 1449 EP 1459 DI 10.1111/j.1467-8624.1991.tb01617.x PG 11 WC Psychology, Educational; Psychology, Developmental SC Psychology GA GX300 UT WOS:A1991GX30000017 PM 1786727 ER PT J AU HANO, O SILVERMAN, HS BLANK, PS MELLITS, ED BAUMGARDNER, R LAKATTA, EG STERN, MD AF HANO, O SILVERMAN, HS BLANK, PS MELLITS, ED BAUMGARDNER, R LAKATTA, EG STERN, MD TI NICARDIPINE PREVENTS CALCIUM LOADING AND OXYGEN PARADOX IN ANOXIC SINGLE-RAT MYOCYTES BY A MECHANISM INDEPENDENT OF CALCIUM-CHANNEL BLOCKADE SO CIRCULATION RESEARCH LA English DT Article DE NICARDIPINE; NIFEDIPINE; DIHYDROPYRIDINE; HYPOXIA; CALCIUM; MYOCYTE ID VENTRICULAR MYOCYTES; HEART-CELLS; ATP AB The protective effect of nicardipine (1 and 4-mu-M) against reoxygenation injury was studied in an unstimulated rat single myocyte oxygen paradox model in comparison with control (no drug) or nifedipine (1-mu-M). Either concentration of nicardipine was strongly protective, approximately doubling the duration of ATP depletion (rigor) that cells could withstand without undergoing hypercontracture when reoxygenated. Nifedipine (1-mu-M), which matched the negative inotropic effect of nicardipine (4-mu-M) (as measured by extent of shortening when stimulated), had no protective effect against reoxygenation injury. Neither drug affected the time to rigor, which is a measure of the rate at which the resting cell consumes its endogenous glycogen stores during anaerobic metabolism. Intracellular calcium, measured with the fluorescent probe indo-1, which partitions into both cytosol and mitochondria, rose progressively throughout the rigor period. This rise in calcium was almost totally suppressed by nicardipine (1-mu-M) but was unaffected by nifedipine. We conclude that nicardipine possesses a direct protective effect on the myocardium not shared by all dihydropyridines. This effect is associated with the prevention of intracellular, and probably mitochondrial, calcium loading but is probably not due to blockade of the L-type calcium channel or reduction of metabolic rate. C1 JOHNS HOPKINS MED INST,DIV CARDIOL,BALTIMORE,MD 21205. JOHNS HOPKINS MED INST,DIV BIOSTAT,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. FU NHLBI NIH HHS [R01 HL-42050, K08 HL-02539, P50 HL-17655] NR 19 TC 28 Z9 31 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD DEC PY 1991 VL 69 IS 6 BP 1500 EP 1505 PG 6 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA GR971 UT WOS:A1991GR97100007 PM 1954672 ER PT J AU STRASSMANN, G BERTOLINI, DR EIDELMAN, O AF STRASSMANN, G BERTOLINI, DR EIDELMAN, O TI INHIBITION OF IMMUNE-REACTIONS INVIVO BY LIPOSOME ASSOCIATED TRANSFORMING GROWTH-FACTOR (TGF) TYPE-BETA-1 SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE LIPOSOME; TGF-BETA; CHARGE INTERACTION; IMMUNITY; INHIBITION ID FACTOR-BETA; HUMAN-PLATELETS; PURIFICATION; COMPLEX; PROTEIN; CELLS AB In view of its potent inhibitory capacity on immune cells in culture, we wished to determine the ability of transforming growth factor (TGF) beta-1 to down-regulate immune responses in vivo. Preliminary experiments suggested that, at the doses used, systemic injection of soluble TGF-beta-1 could not affect bacterial-induced spleen enlargement in mice. Therefore, we sought to utilize a physiochemical property of this molecule, namely its high pI, to determine possible association between the ligand and preformed liposomes possessing an opposite charge. TGF-beta-1 was preferentially associated with negatively charged, but not with neutral, liposomes. These TGF-beta-1 associated liposomes were able to deliver a suppressive signal to indicator cells in vitro. Intravenous injection of TGF-beta-1, associated with liposomes possessing an opposite charge, into mice immunized with heat-killed Corynobacterium parvum significantly reduced the size of the spleen as well as the number of splenocytes. Systemically administered TGF-beta-1 associated liposomes could also inhibit delayed type hypersensitivity reactions to Listeria monocytogenes. These data suggest that appropriately administered, TGF-beta-1 can inhibit immune responses in vivo. C1 NCI,THEORET BIOL LAB,BETHESDA,MD 20892. RP STRASSMANN, G (reprint author), OTSUKA AMER PHARMACEUT INC,MARYLAND RES LABS,9900 MED CTR DR,ROCKVILLE,MD 20850, USA. NR 22 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD DEC PY 1991 VL 86 IS 3 BP 532 EP 536 PG 5 WC Immunology SC Immunology GA GT120 UT WOS:A1991GT12000029 PM 1747960 ER PT J AU MARX, SJ MENCZEL, J CAMPBELL, G AURBACH, GD SPIEGEL, AM NORTON, JA AF MARX, SJ MENCZEL, J CAMPBELL, G AURBACH, GD SPIEGEL, AM NORTON, JA TI HETEROGENEOUS SIZE OF THE PARATHYROID-GLANDS IN FAMILIAL MULTIPLE ENDOCRINE NEOPLASIA TYPE-1 SO CLINICAL ENDOCRINOLOGY LA English DT Article ID TUMORS; CHROMOSOME-11; HYPERPARATHYROIDISM; HYPERPLASIA; GENE AB OBJECTIVE We wished to determine whether there was size heterogeneity of the parathyroid glands in patients with familial multiple endocrine neoplasia type 1 (FMEN1) and primary hyperparathyroidism. DESIGN At the National Institutes of Health we performed a retrospective analysis of parathyroid gland volume either from initial or repeat parathyroid exploration. PATIENTS We studied subjects with FMEN1 and primary hyperparathyroidism. MEASUREMENTS The parathyroid gland volume was estimated from recorded orthogonal diameters. Volume could also be estimated conservatively in many glands for which one or more diameters were not recorded. Reproducibility of volume measurements was tested with a series of clay gland models. Indices of variability (among glands at an operation or among replicate measurements of a clay model) were the ratio of maximum volume/minimum volume and the average standard deviation of the log volume. RESULTS The most complete data were from eight initial operations with three dimensions recorded for all four glands. Volume heterogeneity was indicated by the average ratio of 9.6 for the maximum/minimum gland volume within an operation. The size heterogeneity was even greater among other subgroups. For example, the average ratio of maximum/minimum gland volume within an operation was 17 among five initial operations with four glands removed, but lacking measurements of three dimensions for some glands. Little of this size heterogeneity could be attributed to measurement error since eight replicate measurements on a model gland yielded a maximum/minimum volume ratio of 1.45. CONCLUSIONS There is a wide heterogeneity in size of the parathyroid glands in the patients with FMEN1 and primary hyperparathyroidism. C1 NIDDKD,MOLEC PATHOPHYSIOL BRANCH,BETHESDA,MD. NIH,DIV COMP RES & TECHNOL,STAT & MATH METHODOL LAB,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. NR 22 TC 43 Z9 43 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD DEC PY 1991 VL 35 IS 6 BP 521 EP 526 DI 10.1111/j.1365-2265.1991.tb00938.x PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GT214 UT WOS:A1991GT21400011 PM 1685109 ER PT J AU OSMAN, OT DEVANE, CL GREENBLATT, DJ POTTER, WZ AF OSMAN, OT DEVANE, CL GREENBLATT, DJ POTTER, WZ TI PHARMACOKINETIC AND DYNAMIC CORRELATES OF INTRAVENOUS ALPRAZOLAM CHALLENGE SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID GROWTH-HORMONE RESPONSE; PANIC DISORDER; SECRETION; SERUM; MEN AB The concentration-effect relationship of alprazolam plasma concentration and growth hormone changes was studied in six healthy volunteers by use of three different intravenous bolus doses of alprazolam (0.003, 0.007, and 0.02 mg/kg) in a random blind order. There was a linear increase in peak concentration (C(max)) and area under the curve (AUC) of alprazolam with increasing dose (r = 0.96). There was no significant correlation between alprazolam C(max) and effect on growth hormone measured as either maximum increase or maximum percentage change from baseline. There was, however, an overall positive correlation (r = 0.58) between the AUC values of alprazolam and growth hormone from 0 to 120 minutes, although the relative degree of increased AUC of growth hormone with increasing AUC of alprazolam varied greatly across individuals. The difficulties of interpreting the mechanisms underlying differential growth hormone responses even when concentration of stimulus is controlled are discussed. C1 NIMH,CLIN PHARMACOL SECT,BLDG 10,ROOM 2D46,BETHESDA,MD 20892. NR 21 TC 3 Z9 3 U1 1 U2 1 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 DEC PY 1991 VL 50 IS 6 BP 656 EP 662 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GW587 UT WOS:A1991GW58700004 PM 1752109 ER PT J AU COHEN, C PICKWORTH, WB HENNINGFIELD, JE AF COHEN, C PICKWORTH, WB HENNINGFIELD, JE TI CIGARETTE-SMOKING AND ADDICTION SO CLINICS IN CHEST MEDICINE LA English DT Article ID CONDITIONED PLACE PREFERENCE; TOBACCO WITHDRAWAL SYNDROME; ABUSE LIABILITY; CONTINGENT REINFORCEMENT; SHORTENED CIGARETTES; SUBJECTIVE RESPONSE; DRUG-ABUSE; NICOTINE; SMOKERS; VOLUNTEERS C1 NIDA,ADDICT RES CTR,4940 EASTERN AVE,BALTIMORE,MD 21224. NIDA,CLIN PHARMACOL BRANCH,BALTIMORE,MD 21224. NR 59 TC 4 Z9 4 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-5231 J9 CLIN CHEST MED JI Clin. Chest Med. PD DEC PY 1991 VL 12 IS 4 BP 701 EP 710 PG 10 WC Respiratory System SC Respiratory System GA GQ010 UT WOS:A1991GQ01000007 PM 1747988 ER PT J AU LAMB, ME AF LAMB, ME TI NEBRASKA SYMPOSIUM ON MOTIVATION, VOL 36, SOCIOEMOTIONAL DEVELOPMENT, 1988 - THOMPSON,RA SO CONTEMPORARY PSYCHOLOGY LA English DT Book Review RP LAMB, ME (reprint author), NICHHD,SOCIAL & EMOT DEV SECT,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0010-7549 J9 CONTEMP PSYCHOL JI Comtemp. Psychol. PD DEC PY 1991 VL 36 IS 12 BP 1044 EP 1046 PG 3 WC Psychology, Multidisciplinary SC Psychology GA GU922 UT WOS:A1991GU92200009 ER PT J AU RUDORFER, MV AF RUDORFER, MV TI ECT IN MODERN LITERATURE (CONTINUED) SO CONVULSIVE THERAPY LA English DT Letter RP RUDORFER, MV (reprint author), NIMH,BETHESDA,MD 20892, USA. 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 0749-8055 J9 CONVULSIVE THER JI Convulsive Therapy PD DEC PY 1991 VL 7 IS 4 BP 295 EP 297 PG 3 WC Psychiatry SC Psychiatry GA GR698 UT WOS:A1991GR69800010 ER PT J AU METCALFE, DD AF METCALFE, DD TI FOOD ALLERGY SO CURRENT OPINION IN IMMUNOLOGY LA English DT Article ID COW MILK ALLERGY; MAST-CELL; CHILDREN; PROTEIN; INTOLERANCE; ANTIBODIES; ACTIVATION; CHALLENGE; RESPONSES; INFANTS AB Food allergy is now known to encompass a number of distinct clinical entities that follow the ingestion of specific food or food additives. Research continues to shed light on immediate reactions to foods and food protein-induced enterocolitis of newborns and infants. Adverse reactions to food additives remain an area of health concern. Studies of food allergies have entered an era in which improved clinical design is the hallmark of the research and conclusions may now be drawn reliably. RP METCALFE, DD (reprint author), NIAID,CLIN INVEST LAB,MAST CELL PHYSIOL SECT,BETHESDA,MD 20892, USA. NR 28 TC 43 Z9 45 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD DEC PY 1991 VL 3 IS 6 BP 881 EP 886 DI 10.1016/S0952-7915(05)80007-X PG 6 WC Immunology SC Immunology GA HB637 UT WOS:A1991HB63700007 PM 1793530 ER PT J AU PETTITT, DJ BENNETT, PH SAAD, MF CHARLES, MA NELSON, RG KNOWLER, WC AF PETTITT, DJ BENNETT, PH SAAD, MF CHARLES, MA NELSON, RG KNOWLER, WC TI ABNORMAL GLUCOSE-TOLERANCE DURING PREGNANCY IN PIMA INDIAN WOMEN - LONG-TERM EFFECTS ON OFFSPRING SO DIABETES LA English DT Article; Proceedings Paper CT 3RD INTERNATIONAL WORKSHOP-CONF ON GESTATIONAL DIABETES MELLITUS CY NOV 08-10, 1990 CL CHICAGO, IL SP AMER DIABETES ASSOC ID DIABETES-MELLITUS; PUBERTY; PREVALENCE; OBESITY AB The long-term effects on offspring of abnormal glucose tolerance detected during pregnancy were examined in 552 Pima indian offspring 5-24 yr of age. Fasting hyperinsulinemia, presumably reflecting increased insulin resistance, occurred at an earlier age in the offspring of women who had abnormal glucose tolerance during pregnancy, and these offspring were more obese and had higher rates of abnormal glucose tolerance. When confounding factors were controlled, a 1 mM higher 2-h postload glucose concentration during pregnancy resulted in a significantly higher prevalence of diabetes in the offspring (odds ratio = 1.62). Maternal 2-h glucose concentration during pregnancy was also a significant predictor of glucose concentration during pregnancy in the offspring (P = 0.011). Thus, the metabolic abnormalities associated with the diabetic pregnancy result in long-term effects on the offspring, including insulin resistance, obesity, and diabetes, which in turn may contribute to transmission of risk for developing the same problems in the next generation. C1 CLEVELAND CLIN EDUC FDN,DEPT BIOSTAT & EPIDEMIOL,CLEVELAND,OH 44106. RP PETTITT, DJ (reprint author), NIDDK,DIABET & ARTHRITIS EPIDEMIOL SECT,1550 E INDIAN SCH RD,PHOENIX,AZ 85014, USA. RI Nelson, Robert/B-1470-2012 NR 29 TC 138 Z9 140 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 1991 VL 40 SU 2 BP 126 EP 130 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GV977 UT WOS:A1991GV97700027 PM 1748241 ER PT J AU HILAKIVICLARKE, LA AF HILAKIVICLARKE, LA TI EFFECTS OF TRYPTOPHAN ON DEPRESSION AND AGGRESSION IN STZ-D MICE SO DIABETES LA English DT Article ID STREPTOZOTOCIN-DIABETIC RATS; BRAIN-SEROTONIN SYNTHESIS; BEHAVIORAL DESPAIR; PLASMA TRYPTOPHAN; NORMAL MALES; AMINO-ACIDS; METABOLISM; STRESS; ANTIDEPRESSANTS; INHIBITION AB Streptozocin-induced diabetic (STZ-D) mice have reduced brain concentrations of tryptophan, a precursor substance for 5-hydroxytryptamine, and show lengthened immobility in Porsolt's swim test, a putative animal model of depression. This study investigated whether tryptophan affects behavior in Porsolt's swim test in STZ-administered male National Institutes of Health Swiss mice. In addition, the effect of tryptophan on behavior in the resident-intruder test of aggression was studied. Tryptophan is effective in the treatment of mild depression and may reduce aggressive behavior. Diabetes was induced with injection of 200 mg/kg body wt i.p. STZ. Two weeks after STZ treatment, the mice received 0, 50, and 100 mg/kg i.p. tryptophan 60 min before the swim test. The STZ-administered mice exhibited lengthened immobility in the swim test, and tryptophan caused a dose-related shortening in their immobility times. The control and STZ mice, which were isolated for 1 wk before the resident-intruder test, did not show any difference in the time spent in social investigation or aggressive or defensive behaviors. However, 100 mg/kg i.p. tryptophan 60 min before the test reduced the social interaction and aggressive behavior of the STZ-D mice but increased these behaviors in controls. Results indicate that tryptophan shortens the increased immobility time and reduces social and aggressive behavior in STZ-D mice. Therefore, the reported reductions in the brain-tryptophan concentrations in STZ-D mice may participate in regulating their behavior. C1 NIAAA,CLIN STUDIES LAB,BETHESDA,MD. RP HILAKIVICLARKE, LA (reprint author), GEORGETOWN UNIV,LOMBARDI CANC RES CTR,3800 RESERVOIR RD NW,WASHINGTON,DC 20007, USA. NR 45 TC 3 Z9 3 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 DEC PY 1991 VL 40 IS 12 BP 1598 EP 1602 DI 10.2337/diabetes.40.12.1598 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GU710 UT WOS:A1991GU71000005 PM 1756900 ER PT J AU RUCHKIN, DS JOHNSON, R CANOUNE, H RITTER, W AF RUCHKIN, DS JOHNSON, R CANOUNE, H RITTER, W TI EVENT-RELATED POTENTIALS DURING ARITHMETIC AND MENTAL ROTATION SO ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE EVENT-RELATED POTENTIAL; SLOW WAVE; ARITHMETIC; MENTAL ROTATION ID BRAIN POTENTIALS; TRACKING TASK; SLOW; LOBE; CNV AB In separate studies of arithmetic and mental rotation, similar posterior negative slow waves have been found. This similarity was surprising given the difference in cognitive processing required by these tasks. Furthermore, delayed responses were employed in these studies, so that it was not possible to determine the extent to which the slow wave activity was too late to be associated with processing that was specific to performance of the tasks. This experiment was intended to clarify the task-specific and non-specific nature of the slow wave activity. Subjects performed either an arithmetic or mental rotation task at two levels of difficulty on a random, trial-to-trial basis and gave an immediate response. There were a number of late posterior negativities, each with a different timing and topography, which were sensitive to type of task and/or task difficulty. Some components were associated with early task processing that was synchronized to the stimulus while others, revealed by response-synchronized averaging, were associated with later stages of task processing. There also was post-task activity that was sensitive to the difficulty level of the prior operations. In both tasks, there was a pre-frontal positive wave that persisted over most of the pre-response epoch, evidently related to a process that was active throughout the task. There also was centro-frontal phasic negativity, with a large peak at 380 msec in mental rotation, and a smaller, longer latency peak in arithmetic, apparently related to the complexity of the stimulus. Thus we conclude that arithmetic and mental rotation each elicit task-specific slow wave activity. C1 NINCDS,MED NEUROL BRANCH,COGNIT NEUROSCI SECT,BETHESDA,MD 20892. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT NEUROSCI,BRONX,NY 10461. CUNY HERBERT H LEHMAN COLL,DEPT PSYCHOL,BRONX,NY 10468. RP RUCHKIN, DS (reprint author), UNIV MARYLAND,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21201, USA. FU NINDS NIH HHS [NS11199] NR 35 TC 50 Z9 50 U1 1 U2 5 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 DEC PY 1991 VL 79 IS 6 BP 473 EP 487 DI 10.1016/0013-4694(91)90167-3 PG 15 WC Engineering, Biomedical; Clinical Neurology SC Engineering; Neurosciences & Neurology GA GX283 UT WOS:A1991GX28300006 PM 1721575 ER PT J AU GOMBOCZ, E CHRAMBACH, A AF GOMBOCZ, E CHRAMBACH, A TI SIMULTANEOUS FERGUSON PLOT ANALYSIS, USING ELECTROPHORESIS ON A SINGLE AGAROSE PORE GRADIENT GEL, OF DNA FRAGMENTS CONTAINED IN A MIXTURE SO ELECTROPHORESIS LA English DT Article ID SIZE STANDARDS; FREE MOBILITY; POLYACRYLAMIDE; DEPENDENCE; PARTICLES; APPARATUS; COMPUTER; PROGRAM AB A recent study [1] has demonstrated the feasibility of obtaining Ferguson plots in agarose gel electrophoresis, using a single pore gradient gel. We now report three remedies for defects in the previous experimental approach: (i) UV-absorbing media for density stabilization of the gel is avoided by replacing 5-(N-2,3-dihydroxypropylacetamido)-2,4,6-triiodo-N,N'-bis(2,3-dihydroxypropyl)isophthalamide (Nycodenz) with heavy water; this renders the method applicable to ethidium bromide-labeled DNA. (ii) The density stabilizing medium is kept from having an effect on field strength. (iii) Data collection by uninterrupted time-lapse photography is possible by using an apparatus with a quartz window. These three measures make the method practical for the gel electrophoretic identification and physical characterization of DNA species, potentially up to 50 kb in size. C1 NICHHD,THEORET & PHYS BIOL LAB,MACROMOLEC ANAL SECT,BLDG 10,RM GC101,BETHESDA,MD 20892. NR 25 TC 7 Z9 7 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD DEC PY 1991 VL 12 IS 12 BP 997 EP 1004 DI 10.1002/elps.1150121202 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA HB869 UT WOS:A1991HB86900001 PM 1815960 ER PT J AU BOCEK, P CHRAMBACH, A AF BOCEK, P CHRAMBACH, A TI CAPILLARY ELECTROPHORESIS OF DNA IN AGAROSE SOLUTIONS AT 40-DEGREES-C SO ELECTROPHORESIS LA English DT Note ID POLYACRYLAMIDE; FLUORESCENCE AB DNA fragments ranging from 72 to 1353 bp in length (phi-X174 RF DNA/HaeIII) were separated by capillary electrophoresis in 0.3-2.0% solutions of agarose (Sea-Plaque GTG) at 40-degrees-C. Liquified agarose above its gelling temperature is easily filled and refilled into capillaries. Its background absorbance at 260 nm was sufficiently low to allow for DNA detection at an estimated DNA load of 13 ng/10 components. Sample injection proceeded at 1 kV for 16 s. The internal capillary diameter was 150-mu, the migration path 27 cm. Migration times varied from 5 to 14 min at 185 V/cm. Potentially, the applicability of capillary electrophoresis in agarose solutions can be expected to extend to the entire size range of DNA, in view of the recent demonstration of kb-sized circular DNA separations in agarose solutions, and those of Mb-sized DNA-agarose complexes in linear polyacrylamide solutions. C1 NICHHD,THEORET & PHYS BIOL LAB,MACROMOLEC ANAL SECT,BLDG 10,RM 6C 101,BETHESDA,MD 20892. NR 16 TC 83 Z9 83 U1 0 U2 3 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD DEC PY 1991 VL 12 IS 12 BP 1059 EP 1061 DI 10.1002/elps.1150121212 PG 3 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA HB869 UT WOS:A1991HB86900011 PM 1815959 ER PT J AU LEWIS, SM HESSE, JE AF LEWIS, SM HESSE, JE TI CUTTING AND CLOSING WITHOUT RECOMBINATION IN V(D)J JOINING SO EMBO JOURNAL LA English DT Article DE IG AND TCR GENE ASSEMBLY; SITE-SPECIFIC RECOMBINATION; V(D)J JOINING ID SITE-SPECIFIC RECOMBINATION; T-CELL RECEPTOR; GENE REARRANGEMENT; SIGNAL SEQUENCES; CODING SEGMENTS; DNA; MECHANISM; DELETION AB Open and shut junctions are rare V(D)J joining products in which site-specific recognition, cleavage and re-ligation of joining signals has been uncoupled from recombination. Here, we investigate the relationship of opening and shutting to recombination in two ways. First, we have tested a series of substrates containing one or two joining signals in an in vivo assay. Opening and shutting can be readily observed in substrates that have only one consensus joining signal. Thus, unlike recombination, the majority of open and shut events do not require interactions between two canonical joining signals. Next we examined two-signal substrates to investigate the effect of signal proximity on the frequency of dual open and shut events. These experiments indicate that at least some of the time opening and shutting can be a two-signal transaction. Together these results point to two mechanistically related, but distinct origins for open and shut joining events. In one case, cutting and closing may occur without interaction between two signals. In the other, we suggest that interaction of a canonical signal with 'cryptic' signal-like elements whose sequence is extensively diverged from canonical signals, may bias the V(D)J recombination machinery towards opening and shutting rather than recombination. Open and shut operations could in this way provide a means whereby mistakes in target recognition by the V(D)J recombination machinery produce a non-recombinant outcome, avoiding deleterious chromosomal rearrangements in lymphoid tissues. C1 NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. RP LEWIS, SM (reprint author), CALTECH,DIV BIOL,PASADENA,CA 91125, USA. NR 19 TC 75 Z9 75 U1 0 U2 3 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 DEC PY 1991 VL 10 IS 12 BP 3631 EP 3639 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GQ588 UT WOS:A1991GQ58800008 PM 1935892 ER PT J AU KEEGAN, AD PIERCE, JH ARTRIP, J PLAUT, M PAUL, WE AF KEEGAN, AD PIERCE, JH ARTRIP, J PLAUT, M PAUL, WE TI LIGAND STIMULATION OF TRANSFECTED AND ENDOGENOUS GROWTH-FACTOR RECEPTORS ENHANCES CYTOKINE PRODUCTION BY MAST-CELLS SO EMBO JOURNAL LA English DT Article DE CYTOKINES; IGE; MAST CELLS; RECEPTORS; TYROSINE PHOSPHORYLATION ID SPLENIC NON-B; TYROSINE PHOSPHORYLATION; EGF RECEPTOR; SIGNAL TRANSDUCTION; CROSS-LINKAGE; FC-RECEPTORS; IGE; INTERLEUKIN-3; LINES; DIFFERENTIATION AB IL-3 dependent mast cell lines produce cytokines in response to Fc receptor cross-linkage or to ionomycin. In this study we have observed that cells pre-cultured in IL-3 produce 10-100 times more cytokine after receptor cross-linkage in comparison with IL-4 pre-cultured cells. Although several hematopoetin receptors, including those for IL-3, IL-4 and EPO, do not contain tyrosine kinase domains, their occupancy with ligand causes tyrosine phosphorylation of specific cellular substrates. Therefore, the contribution of tyrosine kinase activation to the ability of an IL-3 dependent mast cell line, CFTL-15, to produce cytokines was analyzed. The CFTL-15 cells were transfected with growth factor receptors containing ligand-inducible tyrosine kinase domains (EGFR and PDGFR, and CSF-IR) or with the EPOR. All of the transfectants were able to proliferate in response to IL-3 or to their respective growth factor and to produce IL-3 in response to IgE receptor cross-linkage. Stimulation of the EGFR and PDGFR transfectants with their respective ligands resulted in the production of IL-3, IL-6, and GMCSF. Stimulation of the CSF-IR or EPOR transfectants with growth factor alone failed to induce cytokine production. However, in co-stimulation assays each of the growth factors enhanced the amount of cytokine produced in response to FC-epsilon-RI cross-linkage. The ability of these stimuli to induce tyrosine phosphorylation in the transfectants was analyzed. Fc-epsilon-RI cross-linkage in the transfectants routinely induced the tyrosine phosphorylation of 145, 86 and 72 kDa proteins, with occasional phosphorylation of 55, 52, and 40 kDa proteins. Costimulation with either EGF or PDGF of transfectants, whose Fc-epsilon-RI was cross linked, led to the enhanced phosphorylation of the 145, 86 (EGF only) and 72 kDa substrates, while co-stimulation with either EPO or CSF-1 enhanced the phosphorylation of the 145 kDa substrate. These results suggest that growth factor treatment increases the 'strength' of signals resulting from Fc-epsilon-RI cross-linkage leading to enhanced cytokine production. C1 JOHNS HOPKINS ASTHMA & ALLERGY CTR,BALTIMORE,MD 21224. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP KEEGAN, AD (reprint author), NIAID,IMMUNOL LAB,BALTIMORE,MD 21224, USA. FU NIAID NIH HHS [AI27906] NR 30 TC 16 Z9 16 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD DEC PY 1991 VL 10 IS 12 BP 3675 EP 3682 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GQ588 UT WOS:A1991GQ58800014 PM 1718740 ER PT J AU SAMULSKI, RJ ZHU, X XIAO, X BROOK, JD HOUSMAN, DE EPSTEIN, N HUNTER, LA AF SAMULSKI, RJ ZHU, X XIAO, X BROOK, JD HOUSMAN, DE EPSTEIN, N HUNTER, LA TI TARGETED INTEGRATION OF ADENOASSOCIATED VIRUS (AAV) INTO HUMAN CHROMOSOME-19 SO EMBO JOURNAL LA English DT Article DE AAV; ADENOASSOCIATED VIRUS; CHROMOSOME; HUMAN; MAPPING ID MAMMARY-TUMOR VIRUS; BABOON ENDOGENOUS VIRUS; I-HYPERSENSITIVE SITES; RETROVIRUS INTEGRATION; HUMAN-CELLS; RECOMBINANT PLASMID; TERMINAL REPEATS; ADENOASSOCIATED VIRUS; PREFERRED TARGETS; HYBRID VIRUS AB A key feature in adeno-associated virus (AAV) replication is efficient integration of the viral genome into host cell DNA to establish latency when helper virus is absent. The steps involved in this process remain largely uncharacterized, even though AAV integration was first documented 20 years ago. Using a protein-DNA binding method we isolated AAV-cellular junction DNA sequences. The cellular component hybridized to a single restriction fragment in the virus-free parental cell line, and also co-migrated with AAV-specific sequences in numerous latently infected cell lines. Analysis of somatic cell hybrids indicated that this cellular sequence maps to the distal portion of the q arm of human chromosome 19. In situ hybridization of AAV DNA to chromosomes from latently infected cells confirms the physical location of AAV integrations to be q13.4-ter of chromosome 19. Sequence analysis of several independent integration sites shows breakpoints occurring within a 100 bp cellular region. This non-pathogenic parvovirus thus appears to establish viral latency by integrating its DNA specifically into one chromosomal region. Such specific integration is so far unique among the eukaryotic DNA viruses. The incorporation of site-specific integration into AAV vector schemes should make this vector system attractive for human gene therapy approaches. C1 MIT,DEPT BIOL,CAMBRIDGE,MA 02139. NHLBI,CTR CANC RES,BETHESDA,MD 20892. NHLBI,BETHESDA,MD 20892. RP SAMULSKI, RJ (reprint author), UNIV PITTSBURGH,DEPT BIOL SCI,PITTSBURGH,PA 15260, USA. OI Brook, John David/0000-0002-5946-6740 FU NIAID NIH HHS [AI 25530-03] NR 70 TC 545 Z9 554 U1 3 U2 15 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 DEC PY 1991 VL 10 IS 12 BP 3941 EP 3950 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GQ588 UT WOS:A1991GQ58800043 PM 1657596 ER PT J AU HUIBREGTSE, JM SCHEFFNER, M HOWLEY, PM AF HUIBREGTSE, JM SCHEFFNER, M HOWLEY, PM TI A CELLULAR PROTEIN MEDIATES ASSOCIATION OF P53 WITH THE E6 ONCOPROTEIN OF HUMAN PAPILLOMAVIRUS TYPE-16 OR TYPE-18 SO EMBO JOURNAL LA English DT Article DE HUMAN PAPILLOMAVIRUS; HPV E6; P53; UBIQUITIN-DEPENDENT PROTEOLYSIS; VIRAL ONCOPROTEIN ID PRIMARY HUMAN KERATINOCYTES; LARGE TUMOR-ANTIGEN; T-ANTIGEN; SV40-TRANSFORMED CELLS; CERVICAL-CARCINOMA; TRANSFORMED-CELLS; DNA; GENE; TRANSCRIPTION; UBIQUITIN AB The E6 protein of human papillomavirus types 16 and 18 (HPV-16 and HPV-18) can stably associate with the p53 protein in vitro. In the presence of rabbit reticulocyte lysate, this association leads to the specific degradation of p53 through the ubiquitin-dependent proteolysis system. We have examined the E6-p53 complex in more detail and have found that association of E6 with p53 is mediated by an additional cellular factor. This factor is present in rabbit reticulocyte lysate, primary human keratinocytes and in each of five human cell lines examined. The factor is designated E6-AP, for E6-associated protein, based on the observation that the E6 proteins of HPV-16 and 18 can form a stable complex with the factor in the absence of p53, whereas p53 association with the factor can be detected only in the presence of E6. Gel filtration and coprecipitation experiments indicate that E6-AP is a monomeric protein of approximately 100 kDa. RP HUIBREGTSE, JM (reprint author), NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892, USA. RI Scheffner, Martin/K-2940-2012 OI Scheffner, Martin/0000-0003-2229-0128 NR 48 TC 554 Z9 563 U1 2 U2 11 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 DEC PY 1991 VL 10 IS 13 BP 4129 EP 4135 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GU645 UT WOS:A1991GU64500018 PM 1661671 ER PT J AU RODBELL, M AF RODBELL, M TI THE BEGINNINGS OF AN ENDOCRINOLOGIST SO ENDOCRINOLOGY LA English DT Editorial Material ID ADENYL CYCLASE SYSTEM; GUANYL NUCLEOTIDES; PLASMA MEMBRANES; RAT LIVER RP RODBELL, M (reprint author), NIEHS,SIGNAL TRANSDUCTION SECT,RES TRIANGLE PK,NC 27709, USA. NR 6 TC 1 Z9 1 U1 1 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1991 VL 129 IS 6 BP 2807 EP 2808 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GT670 UT WOS:A1991GT67000001 PM 1954866 ER PT J AU MERCHENTHALER, I LENNARD, DE AF MERCHENTHALER, I LENNARD, DE TI THE HYPOPHYSIOTROPIC NEUROTENSIN-IMMUNOREACTIVE NEURONAL SYSTEM OF THE RAT-BRAIN SO ENDOCRINOLOGY LA English DT Article ID MEDIAN-EMINENCE; FLUORO-GOLD; HYPOTHALAMUS; HORMONE; IMMUNOHISTOCHEMISTRY; ANTERIOR; PEPTIDE; LESIONS; FIBERS AB The present study describes the distribution of hypophysiotropic neurotensin-immunoreactive (NTi) perikarya in the rat hypothalamus. After peripheral administration of the retrograde tracer Fluoro-Gold, NT immunoreactivity was demonstrated with fluorescence immunocytochemistry using Texas red-labeled avidin. The results indicate that approximately 70% of all NTi neurons that are connected to the hypophysial portal system are located in the arcuate nucleus. Approximately 30% of these hypophysiotropic NTi neurons reside in the parvocellular subdivisions of the paraventricular nucleus. Our results also show that both the arcuate and the paraventricular nuclei contain NTi perikarya that do not project to the median eminence. RP MERCHENTHALER, I (reprint author), NIEHS,MOLEC & INTEGRAT NEUROSCI SCI LAB,FUNCT MORPHOL SECT,MD C4-07,RES TRIANGLE PK,NC 27709, USA. NR 26 TC 31 Z9 31 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1991 VL 129 IS 6 BP 2875 EP 2880 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GT670 UT WOS:A1991GT67000013 PM 1954874 ER PT J AU PARMER, TG ROBERTS, CT LEROITH, D ADASHI, EY KHAN, I SOLAN, N NELSON, S ZILBERSTEIN, M GIBORI, G AF PARMER, TG ROBERTS, CT LEROITH, D ADASHI, EY KHAN, I SOLAN, N NELSON, S ZILBERSTEIN, M GIBORI, G TI EXPRESSION, ACTION, AND STEROIDAL REGULATION OF INSULIN-LIKE GROWTH FACTOR-I (IGF-I) AND IGF-I RECEPTOR IN THE RAT CORPUS-LUTEUM - THEIR DIFFERENTIAL ROLE IN THE 2 CELL-POPULATIONS FORMING THE CORPUS-LUTEUM SO ENDOCRINOLOGY LA English DT Article ID MESSENGER RIBONUCLEIC-ACID; GRANULOSA-CELLS; GENE-EXPRESSION; ESTROUS-CYCLE; PREGNANCY; INVITRO; TISSUE; RNA; STEROIDOGENESIS; PROLIFERATION AB The overall aim of this investigation was to examine the expression and steroidal regulation of insulin-like growth factor-I (IGF-I) and the IGF-I receptor in the rat corpus luteum and to examine the specificity of IGF-I action in the two luteal cell populations. We first examined whether the corpus luteum expresses the IGF-I and IGF-I receptor genes. Using a solution hybridization/RNase protection assay, IGF-I and IGF-I receptor mRNAs were represented by protected bands 224 and 265 bases in length, respectively. In addition, Northern blot analysis showed that, as in liver, rat IGF-I and IGF-I receptor cDNAs hybridized with 7.5-, 1.8-, and 0.8- to 1.2-kilobase transcripts and an 11-kilobase transcript, respectively. Both IGF-I and IGF-I receptor mRNAs were detected on all days of pregnancy tested (days 5-21). Since the rat corpus luteum increases remarkably in size and steroidogenic capacity at midpregnancy due to estradiol stimulation, we determined whether these developmental changes are accompanied by an increased expression of the IGF-I and/or IGF-I receptor genes. Total RNA was isolated from corpora lutea of day 12 hypophysectomized-hysterectomized rats treated with or without estradiol for 3 days. Estradiol caused a clear and marked reduction in IGF-I and IGF-I receptor mRNA. [I-125]IGF-I bound with high specificity and affinity to luteal cell membranes. Large and small cell populations forming corpora lutea of day 3 and 14 pregnant rats were separated by elutriation and used for the determination of binding activity and for cell culture, respectively. IGF-I receptors were found to be localized principally in the large luteal cell population. The small luteal cells had approximately 6.5-fold less IGF-I-binding activity. The difference in binding activity in both cell populations was reflected in the ability of both cell types to respond to IGF-I. IGF-I (25 ng/ml) had a profound effect on the production of progesterone by the large luteal cells. No stimulatory effect of IGF-I on the small luteal cells was observed. Addition of estradiol (10 ng/ml) to the cell culture remarkably enhanced IGF-I stimulation of progesterone biosynthesis by the large luteal cells. In summary, the results of this investigation have revealed that the corpus luteum of the pregnant rat is a major site of expression of both the IGF-I and IGF-I receptor genes. It is the large luteal cells forming the corpus luteum that contain the majority of IGF-I receptors and respond to IGF-I with an increase in steroidogenic output. These results also suggest that whereas IGF-I may play a role in luteal cell function, it does not appear to be responsible for the increase in size and steroidogenic capacity that occurs in the corpus luteum at midpregnancy and which is induced by estradiol. C1 UNIV ILLINOIS, COLL MED, DEPT PHYSIOL & BIOPHYS, 835 S WOLCOTT, CHICAGO, IL 60612 USA. NIDDKS, DIABET BRANCH, BETHESDA, MD 20892 USA. UNIV MARYLAND, SCH MED, DEPT OBSTET GYNECOL, BALTIMORE, MD 21201 USA. UNIV MARYLAND, SCH MED, DEPT PHYSIOL, BALTIMORE, MD 21201 USA. RP GIBORI, G (reprint author), UNIV ILLINOIS, COLL MED, DEPT PHYSIOL & BIOPHYS, 835 S WOLCOTT, CHICAGO, IL 60612 USA. FU NICHD NIH HHS [HD-11119, HD-12356, HD-7336] NR 50 TC 51 Z9 51 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1991 VL 129 IS 6 BP 2924 EP 2932 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GT670 UT WOS:A1991GT67000019 PM 1659518 ER PT J AU TSUTSUMI, K SAAVEDRA, JM AF TSUTSUMI, K SAAVEDRA, JM TI ANGIOTENSIN-II RECEPTOR SUBTYPES IN MEDIAN-EMINENCE AND BASAL FOREBRAIN AREAS INVOLVED IN REGULATION OF PITUITARY-FUNCTION SO ENDOCRINOLOGY LA English DT Article ID ATRIAL-NATRIURETIC-PEPTIDE; CENTRAL NERVOUS-SYSTEM; RAT-BRAIN; ANTERIOR-PITUITARY; SUBFORNICAL ORGAN; BINDING-SITES; PARAVENTRICULAR NUCLEUS; RELEASE; AUTORADIOGRAPHY; VASOPRESSIN AB We used quantitative autoradiography to characterize angiotensin-II (ANG-II) receptor subtypes in areas of the rat basal forebrain involved in pituitary control. ANG binding was totally displaced by the selective AT1 receptor subtype antagonist DuP 753 and was inhibited by dithiothreitol in median eminence, infundibular stem, paraventricular nucleus, subfornical organ, median preoptic nucleus, anterior pituitary, and the forebrain ANG-II receptor band, which extends from the subfornical organ to the vascular organ of the lamina terminalis, including the lamina terminalis and a continuous band of receptors reaching the paraventricular nucleus. In these areas, binding was not affected by the selective AT2 competitors PD 123177 or CGP 42112 A, indicating the presence of AT1 and the absence of AT2 receptors. AT1 binding was higher in the external layer and lateral parts of the median eminence. Conversely, ANG binding in the dura mater encapsulating the pituitary, in the vessels adjacent to this part of the dura mater, presumably branches of the hypophyseal arteries, and in anterior cerebral arteries was displaced by PD 123177 and CGP 42112 A, and was unaffected by dithiothreitol or DuP 753, indicating the presence of AT2 receptors in these structures. Our results implicate AT1 receptors in the central neural regulation of pituitary function. AT2 receptors may play a role in the regulation of blood flow to the basal forebrain and the pituitary gland. C1 NIMH,CLIN SCI LAB,PHARMACOL SECT,BETHESDA,MD 20892. RP SAAVEDRA, JM (reprint author), NIH,BLDG 10,ROOM 2D45,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 42 TC 61 Z9 61 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1991 VL 129 IS 6 BP 3001 EP 3008 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GT670 UT WOS:A1991GT67000028 PM 1954884 ER PT J AU HAKES, DJ BIRCH, NP MEZEY, A DIXON, JE AF HAKES, DJ BIRCH, NP MEZEY, A DIXON, JE TI ISOLATION OF 2 COMPLEMENTARY DEOXYRIBONUCLEIC-ACID CLONES FROM A RAT INSULINOMA CELL-LINE BASED ON SIMILARITIES TO KEX2 AND FURIN SEQUENCES AND THE SPECIFIC LOCALIZATION OF EACH TRANSCRIPT TO ENDOCRINE AND NEUROENDOCRINE TISSUES IN RATS SO ENDOCRINOLOGY LA English DT Article ID PAIRED BASIC RESIDUES; SECRETORY GRANULES; YEAST KEX2; PROTEOLYTIC CONVERSION; REGULATED SECRETION; PROCESSING PROTEASE; SERINE PROTEASES; PITUITARY-CELLS; PROTO-ONCOGENE; MESSENGER-RNA AB We have identified two rat insulinoma cDNAs that code for proteins homologous to the Kex2 dibasic protease of yeast and the mammalian furin gene product. A 5.0-kilobase (kb) cDNA, termed BDP, coding for a 752-amino acid protein and a 2.5-kb cDNA coding for a 636-amino acid protein, which was found to be the rat equivalent of the human insulinoma PC2 protein, were isolated. The proteins encoded by these clones contain a specific N-terminal signal sequence, indicating that both enter the secretory pathway. Neither protein contains a C-terminal transmembrane domain as is found in kex2 and furin, suggesting that the proteins may be soluble. Both proteins contain regions surrounding the active site residues which show amino acid identities to both kex2 (43% for BDP and 41% for RPC2) and furin (57% for BDP and 53% for RPC2). Probes specific for the mRNAs of each protein were used to localize the expression of each protein in endocrine and neuroendocrine tissues. C1 PURDUE UNIV,DEPT BIOCHEM,W LAFAYETTE,IN 47907. NICHHD,DEV NEUROBIOL LAB,CELLULAR NEUROBIOL SECT,BETHESDA,MD 20892. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RP HAKES, DJ (reprint author), UNIV MICHIGAN,SCH MED,DEPT BIOL CHEM,5416 MED SCI,BLDG 1,ANN ARBOR,MI 48109, USA. RI Birch, Nigel/H-2498-2011 OI Birch, Nigel/0000-0002-8417-3587 NR 47 TC 94 Z9 96 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1991 VL 129 IS 6 BP 3053 EP 3063 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GT670 UT WOS:A1991GT67000034 PM 1954888 ER PT J AU RANDERATH, E RANDERATH, K REDDY, R LUCIER, GW AF RANDERATH, E RANDERATH, K REDDY, R LUCIER, GW TI SEXUAL DIMORPHISM OF THE CHROMATOGRAPHIC PROFILES OF I-COMPOUNDS (ENDOGENOUS DEOXYRIBONUCLEIC-ACID MODIFICATIONS) IN RAT-LIVER SO ENDOCRINOLOGY LA English DT Article ID ESTROGEN-BINDING-PROTEINS; SPRAGUE-DAWLEY RATS; DNA MODIFICATIONS; HEPATIC CYTOCHROME-P-450; ANDROGEN RECEPTORS; GROWTH-HORMONE; AGE; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; GONADECTOMY; EXPRESSION AB DNA of all tissues studied thus far in untreated mammals contains as yet structurally unidentified, covalent modifications termed I (indigenous)-compounds, which are detectable by the P-32 postlabeling assay for DNA adducts and increase with age. The purpose of this study was to determine the effects of sex, gonadectomy, and androgen administration on I-compound profiles and levels in order to gain insight into the factors involved in the biosynthesis of these DNA modifications. Liver DNA from various groups of 6-month-old Sprague-Dawley rats (untreated or gonadectomized males and females; animals with or without gonadectomy treated with testosterone propionate) was analyzed by a nuclease P1-enhanced version of the P-32 postlabeling assay. Hepatic I-compound profiles of untreated animals exhibited pronounced sexual dimorphism. In addition to a number of I-compounds that differed quantitatively between sexes, 7 female-specific and 1 male-specific I-compounds were observed. In female rats, the total level amounted to 112 I-compounds in 10(9) DNA nucleotides and exceeded the level in males by 3-fold. Castration feminized and ovariectomy masculinized I-compound profiles and levels. Neonatal testosterone propionate failed to restore the male pattern of I-compounds lost by neonatal castration, so that an androgen-imprinting mechanism did not appear to be involved in the maintenance of the male I-compound phenotype and the suppression of the female pattern. Testosterone propionate administered to intact female animals lowered total I-compound levels significantly. The results indicate that estrogens play a dominant role in regulating sex-dependent formation of I-compounds in rat liver. The dependence of I-compound formation on both age and sex hormones suggests that the levels of these DNA modifications are developmentally controlled. C1 NIEHS,BIOCHEM RISK ANAL LAB,POB 12233,RES TRIANGLE PK,NC 27709. BAYLOR COLL MED,DEPT PHARMACOL,DIV TOXICOL,HOUSTON,TX 77030. RP LUCIER, GW (reprint author), NIEHS,BIOCHEM RISK ANAL LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. FU NCI NIH HHS [R37-CA-32157]; NIA NIH HHS [R01-AG-07750]; NIEHS NIH HHS [P42-ES-04917] NR 45 TC 17 Z9 17 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1991 VL 129 IS 6 BP 3093 EP 3100 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GT670 UT WOS:A1991GT67000038 PM 1954891 ER PT J AU ZHOU, J CHIN, E BONDY, C AF ZHOU, J CHIN, E BONDY, C TI CELLULAR-PATTERN OF INSULIN-LIKE GROWTH FACTOR-I (IGF-I) AND IGF-I RECEPTOR GENE-EXPRESSION IN THE DEVELOPING AND MATURE OVARIAN FOLLICLE SO ENDOCRINOLOGY LA English DT Article ID GRANULOSA-CELLS; HORMONAL-REGULATION; MESSENGER-RNA; RAT OVARY; PROLIFERATION AB We have employed in situ hybridization histochemistry to map the cellular pattern of insulin-like growth factor-I (IGF-I) and the IGF-I receptor gene expression in developing rat ovaries from the time of birth through adulthood, and in response to hypophysectomy and gonadotropin replacement. From the early postnatal period, both IGF-I and IGF-I receptor messenger RNAs (mRNAs) were highly abundant and evenly distributed in granulosa cells of small, growing follicles. In large follicles, however, IGF-I gene expression was heterogeneous. IGF-I mRNA was most abundant in granulosa cells lining the antrum and surrounding the oocyte, but was low or undetectable in mural granulosa cells of Graafian follicles, and was also undetectable in luteinized granulosa cells of corpora lutea. IGF-I receptor mRNA was evenly distributed in developing and mature follicles and was highly abundant in the luteinized granulosa cells of corpora lutea. IGF-I receptor but not IGF-I mRNA was detected in growing oocytes. Hypophysectomy resulted in a decrease and treatment with PMSG resulted in an increase in follicular IGF-I receptor mRNA levels, whereas there was no change in IGF-I mRNA levels in the same protocol. In summary, high levels of both IGF-I and IGF-I receptor gene expression occur in the granulosa cells of actively growing follicles, suggesting that granulosa cell IGF-I may have a role in follicular or oocyte growth. IGF-I gene expression is lost concomitant with follicular enlargement and granulosa cell differentiation, whereas IGF-I receptor gene expression continues at high levels in luteinized granulosa cells, suggesting that IGF effects on differentiated granulosa cell function are due to circulating, not local, hormone. Finally, granulosa cell IGF-I receptor gene expression appears to be regulated by the gonadotropin present in pregnant mare serum. RP ZHOU, J (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N262,BETHESDA,MD 20892, USA. NR 21 TC 139 Z9 143 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1991 VL 129 IS 6 BP 3281 EP 3288 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GT670 UT WOS:A1991GT67000062 PM 1659527 ER PT J AU SCHAAD, NC SHINOHARA, T ABE, T KLEIN, DC AF SCHAAD, NC SHINOHARA, T ABE, T KLEIN, DC TI PHOTONEURAL CONTROL OF THE SYNTHESIS AND PHOSPHORYLATION OF PINEAL MEKA (PHOSDUCIN) SO ENDOCRINOLOGY LA English DT Article ID N-ACETYLTRANSFERASE ACTIVITY; GTP-BINDING PROTEINS; RAT PINEAL; RETINA; ALPHA; CDNA; TRANSDUCIN; ARRESTIN; SUBUNIT; BOVINE AB MEKA is an acidic 33-kilodalton phosphoprotein found in the retina and pineal gland. It is of interest because it forms a cytoplasmic heterotrimer with the beta-gamma-complex of GTP-binding regulatory proteins (G proteins). Accordingly, MEKA may play a role in signal transduction. MEKA is phosphorylated on Ser73 by cAMP-dependent protein kinase. In the present report, MEKA was studied using an antiserum (Anti-32) against MEKA65-96, which can be used to estimate total MEKA and the phosphorylation state of MEKA. It was confirmed that MEKA is rapidly phosphorylated by adrenergic stimulation of pineal glands in organ culture. In addition, total (dephosphorylated) MEKA was observed to increase after a 6-h treatment with norepinephrine or (Bu)2 cAMP, an effect which was dependent upon new protein synthesis. In in vivo studies, it was found that the total amount of MEKA and MEKA phosphorylation were increased at night in the dark, a time when the pineal gland is adrenergically stimulated. The high level of phosphorylation was rapidly reduced when animals were exposed to light, which blocks neural stimulation of the gland. This report provides the first in vivo evidence that MEKA phosphorylation is under physiological control, and that MEKA synthesis is controlled by an adrenergic --> cAMP mechanism which requires protein synthesis. C1 NICHHD,DEV NEUROBIOL LAB,NEUROENDOCRINOL SECT,BETHESDA,MD 20892. NEI,RETINAL CELL & MOLEC BIOL LAB,MOLEC BIOL SECT,BETHESDA,MD 20892. RP KLEIN, DC (reprint author), NIH,BLDG 36,4A07,BETHESDA,MD 20892, USA. OI Shinohara, Toshimichi/0000-0002-7197-9039 NR 42 TC 20 Z9 20 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1991 VL 129 IS 6 BP 3289 EP 3298 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GT670 UT WOS:A1991GT67000063 PM 1659528 ER PT J AU HUFF, J HASEMAN, J AF HUFF, J HASEMAN, J TI LONG-TERM CHEMICAL CARCINOGENESIS EXPERIMENTS FOR IDENTIFYING POTENTIAL HUMAN CANCER HAZARDS - COLLECTIVE DATABASE OF THE NATIONAL-CANCER-INSTITUTE AND NATIONAL-TOXICOLOGY-PROGRAM (1976-1991) SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID RODENT CARCINOGENICITY; TUMOR TRENDS; F344/N RATS; B6C3F1 MICE; BODY-WEIGHT; TOXICITY; NEOPLASMS; SURVIVAL; GROWTH; PERIOD AB The carcinogenicity database used for this paper originated in the late 1960s by the National Cancer Institute (NCI) and since 1978 has been continued and made more comprehensive by the National Toxicology Program (NTP). The extensive files contain, among other sets of information, detailed pathology data on more than 400 long-term (most often 24-month) chemical carcinogenesis studies, comprising nearly 1600 individual experiments having at least 10 million tissue sections that have been evaluated for toxicity and carcinogenicity. Using this data set we have a) determined the concordance in carcinogenic responses between rats and mice to be 74% and between sexes to be 85% (rats) to 87% (mice); b) discovered that using male rats and female mice would have identified correctly 95% of the positive or no evidence chemical carcinogenicity results obtained using the mom extensive protocol; c) established a historical control file of tumor incidence data; d) evaluated the false positive rate in the interpretation of carcinogenesis studies, concluding that this rate is probably no more than 7 to 8%; e) compiled listings of chemicals having like carcinogenic target sites for each of the 37 organs or systems for which histopathology diagnoses have been recorded routinely; f) demonstrated that evaluation of site-specific carcinogenic effects are preferable to doing analyses based on overall (all sites combined) tumor rates; g) learned that few chemicals cause only benign tumors or only liver tumors, the most common target site for chemically induced cancers; h) identified key sources of variability in tumor rates in long-term carcinogenesis studies; i) ascertained that corn oil gavage or gavage per se exhibits little, if any, adverse impact on long-term studies; j) showed that the Salmonella multistrain assay was as good as a battery of four short-term in vitro tests for predicting in vivo carcinogenicity, yet was only 66% concordant with an 89% positive predictivity and a 55% negative predictivity; k) investigated the relationship between chemically induced toxicity and chemically associated carcinogenicity, finding that few chemicals cause tumors only at the highest exposure concentration. These (and other) derived compilations are most useful for maintaining a historic and objective perspective when evaluating the carcinogenicity of contemporary experiments and for identifying potential carcinogenic hazards to humans. RP HUFF, J (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 70 TC 31 Z9 31 U1 0 U2 2 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1991 VL 96 BP 23 EP 31 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA HT428 UT WOS:A1991HT42800005 PM 1820269 ER PT J AU TENNANT, RW AF TENNANT, RW TI THE GENETIC TOXICITY DATABASE OF THE NATIONAL-TOXICOLOGY-PROGRAM - EVALUATION OF THE RELATIONSHIPS BETWEEN GENETIC TOXICITY AND CARCINOGENICITY SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID HAMSTER OVARY CELLS; CHROMATID EXCHANGE TESTS; MOUSE LYMPHOMA CELL; SALMONELLA MUTAGENICITY TESTS; CHROMOSOME ABERRATION; CODED CHEMICALS; 42 CHEMICALS; BONE-MARROW; RODENT CARCINOGENICITY; MUTAGENESIS ASSAY AB The database of the U.S. National Toxicology Program has been developed over approximately two decades, principally focused on substances evaluated for carcinogenicity in rodent bioassays. These assays generally provide data on the relative toxicity and carcinogenicity of chemicals based upon discrete subchronic (13 week) and chronic (104 week) exposures. A major value of these data are that the assay protocols, rodent strains, and technical methodologies have been generally consistent, thus permitting comparisons between assays and chemicals. The genotoxicity data for many of the same chemicals have been developed also using standardized biological systems and protocols. Data for assays including mutagenicity in Salmonella and mouse lymphoma cells, chromosomal aberrations, and sister chromatid exchange in Chinese hamster ovary cells, transformation of Balb/c 3T3 cells, and in vivo cytogenetic effects in rodents have been compiled for many chemicals. The results of all of these assays provide a substantial database for evaluating chemical effects and for defining the complex relationships between mutagenicity and carcinogenicity. RP TENNANT, RW (reprint author), NIEHS,EXPTL CARCINOGENESIS & MUTAGENESIS BRANCH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 48 TC 8 Z9 8 U1 0 U2 0 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1991 VL 96 BP 47 EP 51 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA HT428 UT WOS:A1991HT42800009 PM 1820276 ER PT J AU PIVER, WT AF PIVER, WT TI GLOBAL ATMOSPHERIC CHANGE AND HUMAN HEALTH - PREFACE SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material RP PIVER, WT (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1991 VL 96 BP 129 EP 130 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA HT428 UT WOS:A1991HT42800022 ER PT J AU PIVER, WT AF PIVER, WT TI GLOBAL ATMOSPHERIC CHANGES SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID ULTRAVIOLET-RADIATION; SURFACE WATERS; OZONE; TEMPERATURE; DEPOSITION; MODEL; AIR; METHYLMERCURY; EMISSIONS; SCIENCE AB Increasing concentrations of CO2 and other greenhouse gases in the atmosphere can be directly related to global warming. In terms of human health, because a major cause of increasing atmospheric concentrations of CO2 is the increased combustion of fossil fuels, global warming also may result in increases in air pollutants, acid deposition, and exposure to ultraviolet (UV) radiation. To understand better the impacts of global warming phenomena on human health, this review emphasizes the processes that are responsible for the greenhouse effect, air pollution, acid deposition, and increased exposure to UV radiation. RP PIVER, WT (reprint author), NIEHS,OFF SCI ADVISOR DIRECTOR,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 50 TC 12 Z9 12 U1 3 U2 15 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1991 VL 96 BP 131 EP 137 DI 10.2307/3431221 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA HT428 UT WOS:A1991HT42800023 PM 1820255 ER PT J AU ABERGEL, C CLAVERIE, JM AF ABERGEL, C CLAVERIE, JM TI A STRONG PROPENSITY TOWARD LOOP FORMATION CHARACTERIZES THE EXPRESSED READING FRAMES OF THE D-SEGMENTS AT THE IG H AND T-CELL RECEPTOR LOCI SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article ID 3-DIMENSIONAL STRUCTURE; ANTIGEN RECEPTOR; HEAVY-CHAINS; BETA-CHAIN; GENE; DIVERSITY; SEQUENCE; REGION; REARRANGEMENTS; ELEMENT AB A compilation of murine and human Ig H and TcR beta-D segment sequences was used to estimate the relative usage of the various reading frames and to look for associated sequence patterns. We confirm a strong bias in the expression of the Ig H D segments, with more than 90% (murine) and 85% (human) expressed peptides resulting from a preferred reading frame. Remarkably, 86% (mouse) and 90% (human) of those peptides contain at least one glycine residue. All but one of the atypical preferred D peptides contain serine or proline residues and are found in the immediate vicinity of glycine residues provided by specific J(H) segments. The presence of tyrosine residues is also a characteristic feature of expressed reading frames in both mouse (75%) and human (90%). These results suggest that the constraints of forming a flexible loop within the third complementarity-determining region, is a factor in the preference for a particular reading frame in Ig H D. For the TcR beta-D segments, glycine is specified in most reading frames, and no significant preference is observed. C1 NIH, NATL CTR BIOTECHNOL INFORMAT, NATL LIB MED, BLDG 38A, BETHESDA, MD 20892 USA. NIDDKD, MOLEC BIOL LAB, BETHESDA, MD USA. RP NIH, NATL CTR BIOTECHNOL INFORMAT, NATL LIB MED, BLDG 38A, BETHESDA, MD 20892 USA. NR 39 TC 23 Z9 23 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 EI 1521-4141 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD DEC PY 1991 VL 21 IS 12 BP 3021 EP 3025 DI 10.1002/eji.1830211218 PG 5 WC Immunology SC Immunology GA GV437 UT WOS:A1991GV43700017 PM 1660812 ER PT J AU WAYNE, RK GEORGE, SB GILBERT, D COLLINS, PW KOVACH, SD GIRMAN, D LEHMAN, N AF WAYNE, RK GEORGE, SB GILBERT, D COLLINS, PW KOVACH, SD GIRMAN, D LEHMAN, N TI A MORPHOLOGICAL AND GENETIC-STUDY OF THE ISLAND FOX, UROCYON-LITTORALIS SO EVOLUTION LA English DT Article DE ELECTROPHORESIS; FOX; GENETIC VARIATION; MORPHOLOGY; UROCYON-LITTORALIS ID DNA SEQUENCE RELATEDNESS; MITOCHONDRIAL-DNA; NATURAL-POPULATIONS; RESTRICTION ENDONUCLEASES; ALLOZYME DIVERGENCE; F-STATISTICS; DEER MICE; DIFFERENTIATION; HETEROZYGOSITY; EVOLUTION AB The Island Fox, Urocyon littoralis, is a dwarf form found on six of the Channel Islands located 30-98 km off the coast of southern California. The island populations differ in two variables that affect genetic variation: effective population size and duration of isolation. We estimate that the effective population size of foxes on the islands varies from approximately 150 to 1,000 individuals. Archeological and geological evidence suggests that foxes likely arrived on the three northern islands minimally 10,400-16,000 years ago and dispersed to the three southern islands 2,200-4,300 years ago. We use morphometrics, allozyme electrophoresis, mitochondrial DNA (mtDNA) restriction-site analysis, and analysis of hypervariable minisatellite DNA to measure variability within and distances among island fox populations. The amount of within-population variation is lowest for the smallest island populations and highest for the mainland population. However, the larger populations are sometimes less variable, with respect to some genetic measures, than expected. No distinct trends of variability with founding time are observed. Genetic distances among the island populations, as estimated by the four techniques, are not well correlated. The apparent lack of correspondence among techniques may reflect the effects of mutation rate and colonization history on the values of each genetic measure. C1 NAT HIST MUSEUM LOS ANGELES,MAMMAL SECT,LOS ANGELES,CA 90007. NCI,FREDERICK CANC RES FACIL,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21207. SANTA BARBARA MUSEUM NAT HIST,SANTA BARBARA,CA 93105. USN,FACIL ENGN COMMAND,NAT RESOURCES MANAGEMENT BRANCH,SAN BRUNO,CA 94006. RP WAYNE, RK (reprint author), UNIV CALIF LOS ANGELES,DEPT BIOL,LOS ANGELES,CA 90024, USA. RI Lehman, Niles/A-3434-2008 NR 82 TC 93 Z9 97 U1 3 U2 17 PU SOC STUDY EVOLUTION PI LAWRENCE PA 810 E 10TH STREET, LAWRENCE, KS 66044 SN 0014-3820 J9 EVOLUTION JI Evolution PD DEC PY 1991 VL 45 IS 8 BP 1849 EP 1868 DI 10.2307/2409836 PG 20 WC Ecology; Evolutionary Biology; Genetics & Heredity SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics & Heredity GA GY460 UT WOS:A1991GY46000009 ER PT J AU GARDNER, W MEYER, M KETTERLINUS, R AF GARDNER, W MEYER, M KETTERLINUS, R TI DISCRETE-TIME EVENT HISTORY ANALYSIS USING SEGMENTED HAZARDS SO EXPERIMENTAL AGING RESEARCH LA English DT Article AB Event history analysis is a means of explaining variation in the timing of events in individual life histories. This article describes methods for overcoming two difficult, problems likely to be encountered in applications of event history analysis to studies of aging and human development. First, in many studies the ages of occurrence of critical life events are recorded in discrete units such as years, but the probability distributions of life events are usually specified in continuous-time form. We show how to estimate models for discrete-time data based on an underlying continuous-time specification. Second, the standard distributions for life events often fail to capture the complex age-dependence seen in actual data. We show how to construct a model using segmented hazards, that is, a composite of different functions for different segments of time. To illustrate these points, we study the age of first intercourse of 11,883 subjects from the National Longitudinal Study of Youth. C1 UNIV VIRGINIA,CHARLOTTESVILLE,VA 22903. NICHHD,BETHESDA,MD 20892. NR 26 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0361-073X J9 EXP AGING RES JI Exp. Aging Res. PD WIN PY 1991 VL 17 IS 4 BP 251 EP 260 PG 10 WC Geriatrics & Gerontology; Psychology SC Geriatrics & Gerontology; Psychology GA HV145 UT WOS:A1991HV14500004 PM 1820290 ER PT J AU WEISS, SRB HAAS, K POST, RM AF WEISS, SRB HAAS, K POST, RM TI CONTINGENT TOLERANCE TO CARBAMAZEPINE IS ASSOCIATED WITH LOWERING OF AMYGDALA-KINDLED SEIZURE THRESHOLDS SO EXPERIMENTAL NEUROLOGY LA English DT Article ID RO5-4864 BINDING-SITE; TERM FOLLOW-UP; BENZODIAZEPINE RECEPTOR; RAT-BRAIN; TRIGEMINAL NEURALGIA; MORPHINE-TOLERANCE; DIAZEPAM; CELLS RP WEISS, SRB (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892, USA. RI Haas, Kurt/B-3812-2009 NR 34 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD DEC PY 1991 VL 114 IS 3 BP 300 EP 306 DI 10.1016/0014-4886(91)90155-6 PG 7 WC Neurosciences SC Neurosciences & Neurology GA GU905 UT WOS:A1991GU90500004 PM 1748204 ER PT J AU SINGH, G SUPP, DM SCHREINER, C MCNEISH, J MERKER, HJ COPELAND, NG JENKINS, NA POTTER, SS SCOTT, W AF SINGH, G SUPP, DM SCHREINER, C MCNEISH, J MERKER, HJ COPELAND, NG JENKINS, NA POTTER, SS SCOTT, W TI LEGLESS INSERTIONAL MUTATION - MORPHOLOGICAL, MOLECULAR, AND GENETIC-CHARACTERIZATION SO GENES & DEVELOPMENT LA English DT Article DE INSERTIONAL MUTATION; LIMB DEVELOPMENT; VISCERAL ASYMMETRY; IV LOCUS AND TRANSGENIC MICE ID LEFT RIGHT ASYMMETRY; APICAL ECTODERMAL RIDGE; LIMB MORPHOGENESIS; VISCERAL ASYMMETRY; RETINOIC ACID; MOUSE; BUD; DNA; POLYSPLENIA; INVERSION AB Limb morphogenesis is an excellent model system to study pattern formation during vertebrate development. The legless (lgl) insertional mutation can serve as a tool to analyze specific events in limb development at the embryologic, genetic, and molecular levels. Hemizygous mice of this transgenic line are phenotypically normal, but homozygous mutants are inviable and exhibit limb, brain, and craniofacial malformations, as well as situs inversus. By morphological analysis of mutant hindlimb buds we show absence of a normal apical ectodermal ridge, a structure required for limb bud outgrowth, and an unusually high degree of mesenchymal and ectodermal cell death. Mutant embryos are extremely sensitive to retinoic acid, a known teratogen with a proposed role in limb development. The hindlimb malformations in legless mutants are less severe when bred into the BALB/c background, suggesting the involvement of other strain-specific genes. Molecular analysis of the disrupted region indicates two tightly linked insertion sites. Sequences flanking the transgene insertions have been cloned and mapped to chromosome 12, near the iv (situs inversus viscerum) locus. Consistent with this, complementation tests confirm allelism of lgl and iv and suggest that the transgene insertion may have disrupted more than one gene. Phylogenetically conserved sequences flanking the transgene insertions were identified and used to isolate candidate lgl and iv cDNAs. C1 UNIV N CAROLINA,DEPT PATHOL,CHAPEL HILL,NC 27599. FREE UNIV BERLIN,INST TOXIKOL EMBRYONALPHARMAKOL,W-1000 BERLIN 33,GERMANY. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RP SINGH, G (reprint author), UNIV CINCINNATI,CHILDRENS HOSP,MED CTR,COLL MED,DEPT PEDIAT,CINCINNATI,OH 45229, USA. FU NCI NIH HHS [N01-CO-74101]; NICHD NIH HHS [HD24517]; NIEHS NIH HHS [ES07051] NR 44 TC 65 Z9 65 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD DEC PY 1991 VL 5 IS 12A BP 2245 EP 2255 DI 10.1101/gad.5.12a.2245 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA GU846 UT WOS:A1991GU84600009 PM 1748282 ER PT J AU FITTON, LA DAVIDSON, M MOORE, KJ CHARLES, DJ PRETSCH, W ELSTON, RC BULFIELD, G AF FITTON, LA DAVIDSON, M MOORE, KJ CHARLES, DJ PRETSCH, W ELSTON, RC BULFIELD, G TI THE LIVER ERYTHROCYTE PYRUVATE-KINASE GENE-COMPLEX [PK-1] IN THE MOUSE - REGULATORY GENE-MUTATIONS SO GENETICAL RESEARCH LA English DT Article ID KIDNEY ENZYME; RAT; DETERMINES; STRAINS; MICE; SEQUENCES; ISOZYMES AB Nine enzyme activity variants and one charge variant of liver/erythrocyte pyruvate kinase have been found amongst laboratory and wild mice. Four of the enzyme activity variants were previously reported to be caused by allelic differences in the structural gene, Pk-1s. Analysis of two putative regulatory gene mutations is now reported, both of which map at, or close to, the structural gene on chromosome 3. One of these mutations, in the inbred strain SWR, is tissue specific, affecting enzyme concentration in the liver but not the erythrocyte the other, which arose in a mutation experiment, doubles the enzyme concentration in both tissues. The organization and the nomenclature in the [Pk-1] gene complex are discussed and are compared with the organization of other comprehensively analysed gene complexes in the mouse. C1 AFRC,INST ANIM PHYSIOL & GENET RES,ROSLIN EH25 9PS,MIDLOTHIAN,SCOTLAND. NCI,FREDERICK CANC RES FACIL,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. GESELL STRAHLEN & UMWELTFORSCH MBH,INST SAUGETIERGENET,W-8042 NEUHERBERG,GERMANY. LOUISIANA STATE UNIV,MED CTR,DEPT BIOMETRY & GENET,NEW ORLEANS,LA 70112. FU NCRR NIH HHS [RR03655] NR 28 TC 3 Z9 3 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0016-6723 J9 GENET RES JI Genet. Res. PD DEC PY 1991 VL 58 IS 3 BP 233 EP 241 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA HE645 UT WOS:A1991HE64500006 PM 1802805 ER PT J AU KLAR, AJS BONADUCE, MJ AF KLAR, AJS BONADUCE, MJ TI SWI6, A GENE REQUIRED FOR MATING-TYPE SWITCHING, PROHIBITS MEIOTIC RECOMBINATION IN THE MAT2-MAT3 COLD SPOT OF FISSION YEAST SO GENETICS LA English DT Article ID DOUBLE-STRAND BREAKS; SCHIZOSACCHAROMYCES-POMBE; S-CEREVISIAE; DNA STRANDS; CASSETTES; FREQUENCY; CELLS; TRANSPOSITION; INITIATION; ASYMMETRY AB Mitotic interconversion of the mating-type locus (mat1) of the fission yeast Schizosaccharomyces pombe is initiated by a double-strand break at mat1. The mat2 and mat3 loci act as nonrandom donors of genetic information for mat1 switching such that switches occur primarily (or only) to the opposite mat1 allele. Location of the mat1 "hot spot" for transposition should be contrasted with the "cold spot" of meiotic recombination located within the adjoining mat2-mat3 interval. That is, meiotic interchromosomal recombination in mat2, mat3 and the intervening 15-kilobase region does not occur at all. swi2 and swi6 switching-deficient mutants possess the normal level of double-strand break at mat1, yet they fail to switch efficiently. By testing for meiotic recombination in the cold spot, we found the usual lack of recombination in a swi2 mutant but a significant level of recombination in a swi6 mutant. Therefore, the swi6 gene function is required to keep the donor loci inert for interchromosomal recombination. This finding, combined with the additional result that switching primarily occurs intrachromosomally, suggests that the donor loci are made accessible for switching by folding them onto mat1, thus causing the cold spot of recombination. RP NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, FREDERICK, MD 21701 USA. FU NCI NIH HHS [N01-CO-74101] NR 38 TC 55 Z9 58 U1 0 U2 2 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 DEC PY 1991 VL 129 IS 4 BP 1033 EP 1042 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA GR723 UT WOS:A1991GR72300006 PM 1783290 ER PT J AU MONTGOMERY, EA HUANG, SM LANGLEY, CH JUDD, BH AF MONTGOMERY, EA HUANG, SM LANGLEY, CH JUDD, BH TI CHROMOSOME REARRANGEMENT BY ECTOPIC RECOMBINATION IN DROSOPHILA-MELANOGASTER - GENOME STRUCTURE AND EVOLUTION SO GENETICS LA English DT Article ID UNEQUAL CROSSING-OVER; ELEMENT COPY NUMBER; TRANSPOSABLE ELEMENTS; X-CHROMOSOME; WHITE LOCUS; POPULATION; MUTATIONS; EXCHANGE; CLONING; ACID AB Ectopic recombination between interspersed repeat sequences generates chromosomal rearrangements that have a major impact on genome structure. A survey of ectopic recombination in the region flanking the white locus of Drosophila melanogaster identified 25 transposon-mediated rearrangements from four parallel experiments. Eighteen of the 25 were generated from females carrying X chromosomes heterozygous for interspersed repeat sequences. The cytogenetic and molecular analyses of the rearrangements and the parental chromosomes show: (1) interchromosomal and intrachromosomal recombinants are generated in about equal numbers; (2) ectopic recombination appears to be a meiotic process that is stimulated by the interchromosomal effect to about the same degree as regular crossing over; (3) copies of the retrotransposon roo were involved in all of the interchromosomal exchanges; some copies were involved much more frequently than others in the target region; (4) homozygosis for interspersed repeat sequences and other sequence variations significantly reduced ectopic recombination. C1 NIEHS,GENET LAB,RES TRIANGLE PK,NC 27709. NR 34 TC 121 Z9 126 U1 0 U2 5 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD DEC PY 1991 VL 129 IS 4 BP 1085 EP 1098 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA GR723 UT WOS:A1991GR72300011 PM 1783293 ER PT J AU BYRD, L GROSSMANN, M POTTER, M SHENONG, GLC AF BYRD, L GROSSMANN, M POTTER, M SHENONG, GLC TI CHRONIC MULTIFOCAL OSTEOMYELITIS, A NEW RECESSIVE MUTATION ON CHROMOSOME-18 OF THE MOUSE SO GENOMICS LA English DT Article ID MYELIN BASIC-PROTEIN; SHIVERER MUTANT MICE; BETA-2-ADRENERGIC RECEPTOR; GLUCOCORTICOID RECEPTOR; GROWTH-FACTOR; GENE; ASSIGNMENT; EXPRESSION; DOMAINS; CHAIN C1 NCI,GENET LAB,BLDG 37,RM 2B23,BETHESDA,MD 20892. GUGGENHEIM MAYO MED CTR,ROCHESTER,MN 55901. RI Shen-Ong, Grace/C-8327-2014 FU NCI NIH HHS [N01-CB-71085] NR 15 TC 50 Z9 51 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 DEC PY 1991 VL 11 IS 4 BP 794 EP 798 DI 10.1016/0888-7543(91)90002-V PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA GR016 UT WOS:A1991GR01600002 PM 1686018 ER PT J AU GOLDMAN, D OBRIEN, SJ LUCASDERSE, S DEAN, M AF GOLDMAN, D OBRIEN, SJ LUCASDERSE, S DEAN, M TI LINKAGE MAPPING OF HUMAN POLYMORPHIC PROTEINS IDENTIFIED BY 2-DIMENSIONAL ELECTROPHORESIS SO GENOMICS LA English DT Article ID DIMENSIONAL GEL-ELECTROPHORESIS; HUMAN-LYMPHOCYTE PROTEINS; GENETIC-ANALYSIS; MYOTONIC-DYSTROPHY; MOUSE-BRAIN; POLYPEPTIDES; VARIANTS; CHROMOSOME-19; FIBROBLASTS; LOCI C1 FREDERICK CAN RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. INC DYNCORP,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES,FREDERICK,MD 21702. RP GOLDMAN, D (reprint author), NIAAA,CLIN STUDIES LAB,BETHESDA,MD 20892, USA. RI Dean, Michael/G-8172-2012; Goldman, David/F-9772-2010 OI Dean, Michael/0000-0003-2234-0631; Goldman, David/0000-0002-1724-5405 FU PHS HHS [N01-C0-74102] NR 30 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 0888-7543 J9 GENOMICS JI Genomics PD DEC PY 1991 VL 11 IS 4 BP 875 EP 884 DI 10.1016/0888-7543(91)90010-C PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA GR016 UT WOS:A1991GR01600010 PM 1686020 ER PT J AU CHIN, H KOZAK, CA KIM, HL MOCK, B MCBRIDE, OW AF CHIN, H KOZAK, CA KIM, HL MOCK, B MCBRIDE, OW TI A BRAIN L-TYPE CALCIUM-CHANNEL ALPHA-1 SUBUNIT GENE (CCHL1A2) MAPS TO MOUSE CHROMOSOME-14 AND HUMAN CHROMOSOME-3 SO GENOMICS LA English DT Article ID SKELETAL-MUSCLE; LUNG-CANCER; LOCALIZATION; REGION; DELETION; RECEPTOR; LINKAGE C1 NIAID,MOLEC BIOL LAB,BETHESDA,MD 20892. NCI,GENET LAB,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. RP CHIN, H (reprint author), NINCDS,MOLEC BIOL LAB,BLDG 36,ROOM 3D-02,BETHESDA,MD 20892, USA. NR 30 TC 37 Z9 37 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD DEC PY 1991 VL 11 IS 4 BP 914 EP 919 DI 10.1016/0888-7543(91)90014-6 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA GR016 UT WOS:A1991GR01600014 PM 1664412 ER PT J AU MARCHUK, DA SAULINO, AM TAVAKKOL, R SWAROOP, M WALLACE, MR ANDERSEN, LB MITCHELL, AL GUTMANN, DH BOGUSKI, M COLLINS, FS AF MARCHUK, DA SAULINO, AM TAVAKKOL, R SWAROOP, M WALLACE, MR ANDERSEN, LB MITCHELL, AL GUTMANN, DH BOGUSKI, M COLLINS, FS TI CDNA CLONING OF THE TYPE-1 NEUROFIBROMATOSIS GENE - COMPLETE SEQUENCE OF THE NF1 GENE-PRODUCT SO GENOMICS LA English DT Article ID CYCLIC-AMP PATHWAY; VONRECKLINGHAUSEN NEUROFIBROMATOSIS; PC12 CELLS; RAS P21; SACCHAROMYCES-CEREVISIAE; ACTIVATING PROTEIN; COMPLEMENTARY-DNA; GENOMIC STRUCTURE; GAP; DIFFERENTIATION C1 UNIV MICHIGAN, MED CTR, DEPT INTERNAL MED, ANN ARBOR, MI 48109 USA. UNIV MICHIGAN, MED CTR, HOWARD HUGHES MED INST, ANN ARBOR, MI 48109 USA. NATL CTR BIOTECHNOL INFORMAT, NATL LIB MED, BETHESDA, MD 20894 USA. RP UNIV MICHIGAN, MED CTR, DEPT HUMAN GENET, ANN ARBOR, MI 48109 USA. FU NHGRI NIH HHS [HG00018]; NINDS NIH HHS [NS23410] NR 65 TC 325 Z9 330 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 EI 1089-8646 J9 GENOMICS JI Genomics PD DEC PY 1991 VL 11 IS 4 BP 931 EP 940 DI 10.1016/0888-7543(91)90017-9 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA GR016 UT WOS:A1991GR01600017 PM 1783401 ER PT J AU PISANO, MM CHEPELINSKY, AB AF PISANO, MM CHEPELINSKY, AB TI GENOMIC CLONING, COMPLETE NUCLEOTIDE-SEQUENCE, AND STRUCTURE OF THE HUMAN GENE ENCODING THE MAJOR INTRINSIC PROTEIN (MIP) OF THE LENS SO GENOMICS LA English DT Article ID MESSENGER-RNA; POLYPEPTIDE MIP; FIBER MEMBRANES; EXPRESSION; ACID; DOWNSTREAM; TISSUE C1 NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892. NR 44 TC 53 Z9 54 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 DEC PY 1991 VL 11 IS 4 BP 981 EP 990 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA GR016 UT WOS:A1991GR01600023 PM 1840563 ER PT J AU MASUDA, R YUHKI, N OBRIEN, SJ AF MASUDA, R YUHKI, N OBRIEN, SJ TI MOLECULAR-CLONING, CHROMOSOMAL ASSIGNMENT, AND NUCLEOTIDE-SEQUENCE OF THE FELINE HOMEOBOX HOX3A SO GENOMICS LA English DT Article ID DROSOPHILA HOMEOTIC GENES; DOMESTIC CAT; BOX GENE; EXPRESSION; MURINE; ORGANIZATION; PATTERN; COMPLEX; HOX-3.1; EMBRYO RP MASUDA, R (reprint author), NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. RI MASUDA, RYUICHI/G-5223-2012 NR 55 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 0888-7543 J9 GENOMICS JI Genomics PD DEC PY 1991 VL 11 IS 4 BP 1007 EP 1013 DI 10.1016/0888-7543(91)90026-B PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA GR016 UT WOS:A1991GR01600026 PM 1686012 ER PT J AU MITCHELL, A BALE, AE WANGGE, M YI, HF WHITE, R PIRTLE, RM MCBRIDE, OW AF MITCHELL, A BALE, AE WANGGE, M YI, HF WHITE, R PIRTLE, RM MCBRIDE, OW TI LOCALIZATION OF A DNA SEGMENT ENCOMPASSING 4 TRANSFER-RNA GENES TO HUMAN CHROMOSOME-14Q11 AND ITS USE AS AN ANCHOR LOCUS FOR LINKAGE ANALYSIS SO GENOMICS LA English DT Article ID T-CELL RECEPTOR; TRANSFER-RNA GENES; HEAVY-CHAIN GENES; INSITU HYBRIDIZATION; NUCLEOTIDE-SEQUENCE; HUMAN GENOME; ALPHA-CHAIN; TRANSCRIPTION; CLUSTER; BAND C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. HOWARD HUGHES MED INST,SALT LAKE CITY,UT. UNIV N TEXAS,TEXAS COLL OSTEOPATH MED,DEPT BIOCHEM,DENTON,TX 76203. FU NIGMS NIH HHS [GM 30671] NR 26 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 0888-7543 J9 GENOMICS JI Genomics PD DEC PY 1991 VL 11 IS 4 BP 1063 EP 1070 DI 10.1016/0888-7543(91)90033-B PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA GR016 UT WOS:A1991GR01600033 PM 1686015 ER PT J AU CHIAVEROTTI, TA BATTULA, N MONNAT, RJ AF CHIAVEROTTI, TA BATTULA, N MONNAT, RJ TI RAT HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE CDNA CLONING AND SEQUENCE-ANALYSIS SO GENOMICS LA English DT Note ID GUANINE PHOSPHORIBOSYLTRANSFERASE; ESCHERICHIA-COLI; DEFICIENCY; ENZYMES C1 UNIV WASHINGTON,DEPT PATHOL,SM-30,SEATTLE,WA 98195. NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. FU NCI NIH HHS [R29 CA48022] NR 9 TC 17 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD DEC PY 1991 VL 11 IS 4 BP 1158 EP 1160 DI 10.1016/0888-7543(91)90046-H PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA GR016 UT WOS:A1991GR01600046 PM 1783384 ER PT J AU KUMAR, R POWELL, B TANI, N NALIBOFF, B METTER, EJ AF KUMAR, R POWELL, B TANI, N NALIBOFF, B METTER, EJ TI PERCEPTUAL DYSFUNCTION IN HEMIPLEGIA AND AUTOMOBILE DRIVING SO GERONTOLOGIST LA English DT Article DE STROKE; PERCEPTUAL DEFICITS; TRAINING FOR OLDER DRIVERS ID BRAIN-DAMAGE C1 VET ADM MED CTR,DEPT REHABIL MED,SEPULVEDA,CA 91343. VET ADM MED CTR,DEPT PSYCHOL,SEPULVEDA,CA 91343. UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT ANESTHESIOL,LOS ANGELES,CA 90024. NATL INST AGING,GERONTOL RES CTR,BALTIMORE,MD. RP KUMAR, R (reprint author), VET ADM MED CTR,REHABIL MED SERV,16111 PLUMMER ST,SEPULVEDA,CA 91343, USA. NR 13 TC 9 Z9 9 U1 2 U2 2 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD DEC PY 1991 VL 31 IS 6 BP 807 EP 810 PG 4 WC Gerontology SC Geriatrics & Gerontology GA GV145 UT WOS:A1991GV14500011 PM 1800254 ER PT J AU SAMET, JM PATHAK, DR MORGAN, MV KEY, CR VALDIVIA, AA LUBIN, JH AF SAMET, JM PATHAK, DR MORGAN, MV KEY, CR VALDIVIA, AA LUBIN, JH TI LUNG-CANCER MORTALITY AND EXPOSURE TO RADON PROGENY IN A COHORT OF NEW-MEXICO UNDERGROUND URANIUM MINERS SO HEALTH PHYSICS LA English DT Article ID DISEASE MORTALITY; MODELS; RISK AB A cohort of 3469 males with at least 1 y of underground uranium mining experience in New Mexico was assembled and mortality followed up through 31 December 1985. The mean and median cumulative exposures for the cohort were 0.39 J h m-3 and 0.12 J h m-3 (111.4 and 35.0 Working Level Months [WLM]), respectively. Overall, mortality in the cohort was significantly increased (standardized mortality ratio [SMR] = 1.1, 95% confidence interval [CI] = 1.02-1.2) relative to the general population of the state. By cause, significant increases were observed for lung cancer (SMR = 4.0, 95% CI 3.1-5.1) and for external causes of death (SMR = 1.5, 95% CI 1.3-1.7). The risk of lung cancer increased for exposure categories above 100 WLM; the excess relative risk increased by 0.5% per mJ h m-3, 95% CI 0.2-1.5 (1.8% per WLM, 95% CI 0.7-5.4). Data were consistent with a multiplicative interaction between smoking and exposure to Rn progeny in an exponential relative risk model. The risk of lung cancer varied substantially with age at observation; the odds ratios rose more steeply with exposure to Rn progeny for those less than age 55 y at observation. C1 UNIV NEW MEXICO, MED CTR, CTR CANC, NEW MEXICO TUMOR REGISTRY, ALBUQUERQUE, NM 87131 USA. UNIV NEW MEXICO, MED CTR, DEPT FAMILY COMMUNITY & EMERGENCY MED, ALBUQUERQUE, NM 87131 USA. UNIV NEW MEXICO, MED CTR, DEPT PATHOL, ALBUQUERQUE, NM 87131 USA. GRANTS CLIN, GRANTS, NM 87020 USA. NCI, BIOSTAT BRANCH, EPIDEMIOL METHODS SECT, BETHESDA, MD 20892 USA. RP SAMET, JM (reprint author), UNIV NEW MEXICO, MED CTR, DEPT MED, ALBUQUERQUE, NM 87131 USA. FU NCI NIH HHS [N01 CN-55426] NR 19 TC 66 Z9 68 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD DEC PY 1991 VL 61 IS 6 BP 745 EP 752 DI 10.1097/00004032-199112000-00005 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA GT922 UT WOS:A1991GT92200005 PM 1659563 ER PT J AU DIBISCEGLIE, AM GOODMAN, ZD ISHAK, KG HOOFNAGLE, JH MELPOLDER, JJ ALTER, HJ AF DIBISCEGLIE, AM GOODMAN, ZD ISHAK, KG HOOFNAGLE, JH MELPOLDER, JJ ALTER, HJ TI LONG-TERM CLINICAL AND HISTOPATHOLOGICAL FOLLOW-UP OF CHRONIC POSTTRANSFUSION HEPATITIS SO HEPATOLOGY LA English DT Article ID POST-TRANSFUSION HEPATITIS; NON-B-HEPATITIS; CHRONIC NON-A; RECOMBINANT INTERFERON-ALFA; HEPATOCELLULAR-CARCINOMA; CONTROLLED TRIAL; C VIRUS; MULTICENTER AB We have evaluated the clinical and histopathological outcomes of patients who contracted chronic non A, non B hepatitis as a result of transfusions administered during heart surgery at the National Institutes of Health. Posttransfusion hepatitis developed in 65 of 1,070 (6.1%) patients and became chronic in 45 (69%) of those cases. Antibody to hepatitis C virus was detectable in 53 patients (82%) with posttransfusion non A, non B hepatitis. Thirty-three patients with chronic non A, non B hepatitis agreed to liver biopsy (group 1). In addition, six other patients with chronic posttransfusion non A, non B hepatitis were evaluated (group 2). These 39 patients were followed between 1 and 24 yr (mean = 9.7 yr). Cirrhosis developed in 8 patients (20%) between 1.5 and 16 yr after blood transfusion. Of the 33 patients in group 1, 11 (33%) died during follow-up. In two cases (6%), this was related to liver failure. At this writing, two additional patients (6%) have decompensated cirrhosis and one (3%) has debilitating fatigue. Twenty of 33 patients (61%) with histological evidence of chronic active hepatitis or cirrhosis are asymptomatic and have no clinical evidence of liver disease. Thus chronic non A, non B posttransfusion hepatitis appeared to be due to hepatitis C virus infection in most cases. It was associated with the development of cirrhosis in approximately 20% of cases and end-stage liver disease in 12% of patients followed prospectively. Most patients with histological evidence of cirrhosis or chronic active hepatitis, however, had minimal clinical evidence of liver disease within the time frame of this study. C1 ARMED FORCES INST PATHOL,DEPT HEPAT & GASTROINTESTINAL PATHOL,WASHINGTON,DC 20306. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,IMMUNOL SECT,BETHESDA,MD 20892. RP DIBISCEGLIE, AM (reprint author), NIADDKD,LIVER DIS SECT,BLDG 10,ROOM 4052,BETHESDA,MD 20892, USA. RI Jepsen, Peter/A-2593-2010 OI Jepsen, Peter/0000-0002-6641-1430 NR 19 TC 530 Z9 534 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 1991 VL 14 IS 6 BP 969 EP 974 DI 10.1016/0270-9139(91)90113-A PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GT559 UT WOS:A1991GT55900002 PM 1959884 ER PT J AU OKUDA, H TAVOLONI, N BLASCHKE, TF KIANG, CL JONES, MJT WAGGONER, JG SARDANA, MK SASSA, S SHRAGER, RI BERK, PD AF OKUDA, H TAVOLONI, N BLASCHKE, TF KIANG, CL JONES, MJT WAGGONER, JG SARDANA, MK SASSA, S SHRAGER, RI BERK, PD TI PHENOBARBITAL DOES NOT INCREASE EARLY LABELING OF BILIRUBIN FROM 4-[C-14]-DELTA-AMINOLEVULINIC ACID IN MAN AND RAT SO HEPATOLOGY LA English DT Article ID GILBERTS SYNDROME; DRUG-METABOLISM; CARBON-MONOXIDE; LIVER; BILE; DIGLUCURONIDE; GLUTATHIONE; CHOLESTASIS; DIAGNOSIS; ISOMERS AB Delta-Aminolevulinic acid-4-[C-14] and [H-3]-bilirubin were administered intravenously to five patients with Gilbert's syndrome and four healthy control subjects on two occasions: before and on days 10 through 14 of a course of phenobarbital (2.5 mg/kg/day). The resulting curves of [H-3]-bilirubin and [C-14]-bilirubin in plasma were analyzed by computer to determine a number of parameters of physiological interest. As expected, phenobarbital produced a highly significant fall in the plasma concentration of unconjugated bilirubin as a result of a significant increase in hepatic bilirubin clearance in all subjects; plasma bilirubin turnover was unaltered. Surprisingly, the drug produced no change in the incorporation of [C-14]-delta-aminolevulinic acid into [C-14]-early labeled bilirubin. To explain this unexpected finding, the effects of phenobarbital (75 mg/kg/day for 6 days) on incorporation of [C-14]-delta-aminolevulinic acid and 2-[C-14]-glycine into [C-14]-early labeled bilirubin and on the activity of the enzyme delta-aminolevulinic acid synthase were studied in nonfasted, adult, male Sprague-Dawley rats. At the dose and duration of treatment used, phenobarbital administration increased total hepatic delta-aminolevulinic acid synthase activity and produced a significant increase of 70% in the incorporation of [C-14]-glycine into early labeled bilirubin. By contrast, no increase in the incorporation of [C-14]-delta-aminolevulinic acid into early labeled bilirubin was observed. These data suggest that delta-aminolevulinic acid is an inappropriate precursor for studies of the rate of heme biosynthesis, presumably because it bypasses delta-aminolevulinic acid synthase, the physiological rate-limiting enzyme in the heme biosynthetic pathway. C1 CUNY MT SINAI SCH MED,DEPT MED,DIV LIVER DIS,BOX 1039,1 GUSTAVE L LEVY PL,NEW YORK,NY 10029. CUNY MT SINAI SCH MED,DEPT BIOCHEM,NEW YORK,NY 10029. NCI,METAB BRANCH,BETHESDA,MD 20892. NIDDKD,DIS LIVER SECT,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. ROCKEFELLER UNIV,NEW YORK,NY 10021. FU NIDDK NIH HHS [DK-26438] NR 61 TC 6 Z9 6 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 1991 VL 14 IS 6 BP 1153 EP 1160 DI 10.1016/0270-9139(91)90143-J PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GT559 UT WOS:A1991GT55900032 PM 1959865 ER PT J AU JONES, EA AF JONES, EA TI BENZODIAZEPINE RECEPTOR LIGANDS AND HEPATIC-ENCEPHALOPATHY - FURTHER UNFOLDING OF THE GABA STORY SO HEPATOLOGY LA English DT Editorial Material ID RABBIT MODEL; ANIMAL-MODEL; ANTAGONIST FLUMAZENIL; ELEVATED LEVELS; LIVER-FAILURE; COMPLEX; COMA; RATS; ACID RP JONES, EA (reprint author), NIDDKD,LIVER UNIT,BLDG 10,ROOM 4D52,BETHESDA,MD 20892, USA. NR 35 TC 13 Z9 13 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 1991 VL 14 IS 6 BP 1286 EP 1290 DI 10.1016/0270-9139(91)90162-O PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GT559 UT WOS:A1991GT55900051 PM 1660022 ER PT J AU DECOSTA, BR LEWIN, A SCHOENHEIMER, JA SKOLNICK, P RICE, KC AF DECOSTA, BR LEWIN, A SCHOENHEIMER, JA SKOLNICK, P RICE, KC TI A PRACTICAL SYNTHESIS OF ISOTOPICALLY LABELED 1-(4-ISOTHIOCYANATOPHENYL)-4-(TERT-BUTYL)-2,6,7-TRIOXABICYCLO-[2.2.2]OCT ANE, A PROBE FOR THE BENZODIAZEPINE RECEPTOR-COUPLED CHLORIDE IONOPHORE SO HETEROCYCLES LA English DT Article ID GABA RECEPTOR; BINDING; HETEROGENEITY; SITES AB An efficient synthesis of high specific activity [H-3] 1-(4-isothiocyanato-3,5-ditritiophenyl)-4-(1-butyl)-2,6,7-trioxabicyclo[2.2.2]octane ([H-3]-1), an affinity ligand for the benzodiazepine (BZ)-coupled gamma-aminobutyric acid (GABA)-gated chloride channel, was achieved starting with methyl p-aminobenzoate and 3-(t-butyl)-3-oxetanemethanol. A key step in the reaction sequence utilized the azide group as a latent aromatic amine allowing synthesis of 1-(4-amino-3,5-ditritiophenyl)-4-(t-butyl)-2,6,7-trioxabicyclo[2.2.2]octane ([H-3]-18) via boron trifluoride etherate catalysed isomerization of 3-(t-butyl)-3-(3,5-dibromo-4-azidobenzoyloxymethyl)-oxetane (15) to 1-(3,5-dibromo-4-azidophenyl)-4-(t-butyl)-2,6,7-trioxabicyclo[2.2.2]octane (17) Model experiments performed in an attempt to use unprotected or trifluoroacetamide protected aromatic amines in this sequence of reactions were unsuccessful. C1 NIDDKD,NEUROSCI LAB,BETHESDA,MD 20892. RP DECOSTA, BR (reprint author), NIDDKD,MED CHEM LAB,BETHESDA,MD 20892, USA. NR 22 TC 2 Z9 2 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0385-5414 J9 HETEROCYCLES JI Heterocycles PD DEC 1 PY 1991 VL 32 IS 12 BP 2343 EP 2355 PG 13 WC Chemistry, Organic SC Chemistry GA HB822 UT WOS:A1991HB82200008 ER PT J AU WIEDER, R AF WIEDER, R TI CRYOPRESERVED PRIMATE BONE-MARROW CELLS CAN BE USED FOR RETROVIRAL-MEDIATED GENE-TRANSFER SO HUMAN GENE THERAPY LA English DT Article ID STEM-CELLS; W/WV MICE; EXPRESSION; EFFICIENCY; VECTORS; DNA AB Retroviral-mediated gene transfer into Rhesus monkey bone marrow cells, which were cryopreserved, stored, and then transduced at the time of thawing, was studied for potential application in gene therapy protocols. Albumin density gradient fractionation was used to define subpopulations of cryopreserved cells transduced by a murine retroviral vector. The transfer of the bacterial neomycin phosphotransferase gene into Rhesus monkey bone marrow that was cryopreserved and thawed was found to be preferential in a light-density population enriched for granulocyte-macrophage colony-forming units (CFU-GM). These results are similar to results obtained with freshly harvested bone marrow in which this population is enriched for CD34 antigen-positive cells, as well as for cells that were undergoing cell division. This method may be useful in enriching for transduced precursors in future gene transfer experiments in primates. C1 NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892. NR 16 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD WIN PY 1991 VL 2 IS 4 BP 323 EP 326 DI 10.1089/hum.1991.2.4-323 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA GY743 UT WOS:A1991GY74300004 PM 1724383 ER PT J AU LEDLEY, FD WOO, SLC FERRY, GD WHISENNAND, HH BRANDT, ML DARLINGTON, GJ DEMMLER, GJ FINEGOLD, MJ POKORNY, WJ ROSENBLATT, H SCHWARTZ, P ANDERSON, WF MOEN, RC AF LEDLEY, FD WOO, SLC FERRY, GD WHISENNAND, HH BRANDT, ML DARLINGTON, GJ DEMMLER, GJ FINEGOLD, MJ POKORNY, WJ ROSENBLATT, H SCHWARTZ, P ANDERSON, WF MOEN, RC TI HEPATOCELLULAR TRANSPLANTATION IN ACUTE HEPATIC-FAILURE AND TARGETING GENETIC-MARKERS TO HEPATIC CELLS SO HUMAN GENE THERAPY LA English DT Article ID BONE-MARROW TRANSPLANTATION; ACUTE LIVER-FAILURE; INTRASPLENIC HEPATOCYTE TRANSPLANTATION; MICROCARRIER-ATTACHED HEPATOCYTES; HUMAN PHENYLALANINE-HYDROXYLASE; PANCREATIC EXOCRINE CELLS; UW-SOLUTION; RAT SPLEEN; LEUKEMIA-VIRUS; HUMAN-DISEASE C1 BAYLOR COLL MED,DEPT PATHOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT SURG,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MICROBIOL & IMMUNOL,HOUSTON,TX 77030. HOWARD HUGHES MED INST,COCONUT GROVE,FL 33133. TEXAS CHILDRENS HOSP,HOUSTON,TX 77030. NIH,BETHESDA,MD 20892. GENET THERAPY INC,BETHESDA,MD. RP LEDLEY, FD (reprint author), BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030, USA. NR 183 TC 29 Z9 29 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 WIN PY 1991 VL 2 IS 4 BP 331 EP 358 DI 10.1089/hum.1991.2.4-331 PG 28 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA GY743 UT WOS:A1991GY74300005 PM 1665349 ER PT J AU ROBBINS, JH AF ROBBINS, JH TI XERODERMA-PIGMENTOSUM COMPLEMENTATION GROUP-H IS WITHDRAWN AND REASSIGNED TO GROUP-D SO HUMAN GENETICS LA English DT Letter ID PATIENT RP ROBBINS, JH (reprint author), NCI,DERMATOL BRANCH,BLDG 10,ROOM 12N238,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 8 TC 13 Z9 13 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 DEC PY 1991 VL 88 IS 2 BP 242 EP 242 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GV390 UT WOS:A1991GV39000025 PM 1757099 ER PT J AU TRAVIS, WD KWONCHUNG, KJ KLEINER, DE GEBER, A LAWSON, W PASS, HI HENDERSON, D AF TRAVIS, WD KWONCHUNG, KJ KLEINER, DE GEBER, A LAWSON, W PASS, HI HENDERSON, D TI UNUSUAL ASPECTS OF ALLERGIC BRONCHOPULMONARY FUNGAL DISEASE - REPORT OF 2 CASES DUE TO CURVULARIA ORGANISMS ASSOCIATED WITH ALLERGIC FUNGAL SINUSITIS SO HUMAN PATHOLOGY LA English DT Article DE ALLERGIC BRONCHOPULMONARY FUNGAL DISEASE; ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS; ALLERGIC ASPERGILLUS SINUSITIS; FUNGAL SINUSITIS, ASTHMA; DEMATIACEOUS FUNGUS; CURVULARIA-LUNATA, CURVULARIA-SENEGALENSIS; BRONCHOCENTRIC GRANULOMATOSIS ID NEWLY RECOGNIZED FORM; ASPERGILLUS SINUSITIS; BRONCHOCENTRIC GRANULOMATOSIS; BRONCHIOLITIS OBLITERANS; BRONCHIAL-ASTHMA; PNEUMONIA; CONSEQUENT; INFECTION; DIAGNOSIS; CURE C1 NIAID,CLIN INVEST LAB,CLIN MYCOL SECT,BETHESDA,MD 20892. MT SINAI MED CTR,DEPT OTOLARYNGOL,NEW YORK,NY 10029. NCI,SURG BRANCH,BETHESDA,MD 20892. NIH,CTR CLIN,BETHESDA,MD 20892. RP TRAVIS, WD (reprint author), NCI,PATHOL LAB,BLDG 10,ROOM 2N212,BETHESDA,MD 20892, USA. NR 48 TC 52 Z9 53 U1 1 U2 1 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 DEC PY 1991 VL 22 IS 12 BP 1240 EP 1248 DI 10.1016/0046-8177(91)90106-Y PG 9 WC Pathology SC Pathology GA GX837 UT WOS:A1991GX83700008 PM 1748430 ER PT J AU SCHMITT, JM AF SCHMITT, JM TI SIMPLE PHOTON DIFFUSION ANALYSIS OF THE EFFECTS OF MULTIPLE-SCATTERING ON PULSE OXIMETRY SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article ID ARTERIAL OXYGEN-SATURATION AB Photon diffusion theory is used to derive analytical expressions that relate the ac-dc intensity ratios measured by transmission-mode and reflectance-mode pulse oximeters to arterial oxygen saturation (S(a)O2). The effects of multiple scattering are examined by comparing the results of the photon diffusion analysis with those obtained using an analysis based on the Beer-Lambert law which neglects scattering. We show that the difference between the average lengths of the paths travelled by red and infrared photons makes the calibration curve of oximeters sensitive to the total attenuation coefficients of the tissue in the two wavelength bands, as well as to absorption by the pulsating arterial blood. Therefore, the shape of the calibration curve is affected by tissue blood volume, source-detector placement, and other variables that change the wavelength dependence of the attenuation coefficient of the tissue. After evaluating the relationship between S(a)O2 and the red/IR ac-dc ratio (R) under a variety of physiological conditions, we conclude that, for oximeters utilizing fixed calibration curves based on measurements obtained from normal subjects, errors introduced by interfering variables should be less than a few percent when S(a)O2 exceeds 70%. Predicted errors at lower oxygen saturation values are substantially greater because R is much more sensitive to interfering variables in this measurement range. RP SCHMITT, JM (reprint author), NIH, NATL CTR RES RESOURCES, BIOMED ENGN & INSTRUMENTAT PROGRAM, BETHESDA, MD 20892 USA. NR 18 TC 74 Z9 77 U1 1 U2 5 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD DEC PY 1991 VL 38 IS 12 BP 1194 EP 1203 DI 10.1109/10.137285 PG 10 WC Engineering, Biomedical SC Engineering GA GT086 UT WOS:A1991GT08600004 PM 1774081 ER PT J AU GIACOMINI, P CIUCCI, A NICOTRA, MR NASTRUZZI, C FERIOTTO, G APPELLA, E GAMBARI, R POZZI, L NATALI, PG AF GIACOMINI, P CIUCCI, A NICOTRA, MR NASTRUZZI, C FERIOTTO, G APPELLA, E GAMBARI, R POZZI, L NATALI, PG TI TISSUE-SPECIFIC EXPRESSION OF THE HLA-DRA GENE IN TRANSGENIC MICE SO IMMUNOGENETICS LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-II GENES; MONOCLONAL-ANTIBODIES; FUNCTIONAL EXPRESSION; ALPHA-CHAIN; IA ANTIGENS; MHC; CELLS; TOLERANCE; INVIVO AB Transgenic mice were produced containing a 33 kilobase (kb) DNA fragment encompassing the five exons and all the known regulatory regions of the class II HLA-DRA gene. The transgene displayed regulated expression [constitutive and interferon-gamma (IFN)-gamma induced] of the human products in most mouse tissues. The tissue distribution of the DRA transgene products more closely resembled that of their mouse homologues, the endogenous H-2 Ea products, than the wider distribution of DRA products in humans. This was evident in several tissues (endothelia of small vessels, especially those of glomerular capillaries, Kupffer cells, and epithelial cells lining the gastrointestinal tract), known to differentially express class II molecules in the two species. Thus, the wider human specific pattern of expression requires an exact cis/trans complementation which is incompletely reconstituted in transgenic mice, suggesting that human-specific cis-acting elements may have arisen during evolution to direct the expression of class II genes to those anatomical regions which usually lack them in the mouse. The only example of aberrant expression of the DRA gene in the present series of transgenic mice was in the dendritic and/or epithelial cells of the thymic cortex, which displayed greatly reduced DR-alpha-levels in spite of a normal expression of the endogenous E-alpha-molecules. C1 CNR,INST BIOMED TECHNOL,ROME,ITALY. BIOTECHNOL CTR,BIOCHEM LAB,FERRARA,ITALY. NIH,CELL BIOL LAB,BETHESDA,MD 20892. UNIV ROME LA SAPIENZA,DEPT BIOPATHOL,I-00185 ROME,ITALY. RP GIACOMINI, P (reprint author), REGINA ELENA INST CANC RES,IMMUNOL LAB,VIA MESSI DORO 156,I-00158 ROME,ITALY. RI Gambari, Roberto/F-9555-2015; Nastruzzi, Claudio/N-4230-2015; Giacomini, Patrizio/K-5217-2016 OI Gambari, Roberto/0000-0001-9205-6033; Nastruzzi, Claudio/0000-0001-9552-0807; Giacomini, Patrizio/0000-0001-6109-1709 NR 33 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD DEC PY 1991 VL 34 IS 6 BP 385 EP 391 DI 10.1007/BF01787489 PG 7 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA GT095 UT WOS:A1991GT09500006 PM 1721044 ER PT J AU GERMANA, S SHINOHARA, N AF GERMANA, S SHINOHARA, N TI QA-1/TLA REGION ALLOANTIGEN-SPECIFIC CTL WITH ALPHA-BETA-RECEPTOR SO IMMUNOLOGY LA English DT Article ID T-CELL RECEPTOR; TOXIC LYMPHOCYTES-T; GAMMA-DELTA; MONOCLONAL-ANTIBODIES; H-2 HAPLOTYPES; ANTIGEN; POPULATIONS; RECOGNITION; COMPLEX; PRODUCT AB Recent studies involving T cells that express gamma-delta-T-cell receptor (gamma-delta-TcR) have raised the possibility that Qa-1/Tla region class I major histocompatibility complex (MHC)-like molecules are antigen-presenting molecules for gamma-delta-TcR. In this report, cytotoxic T lymphocyte (CTL) clones specific for a Qa-1/Tla region gene product were isolated from a bulk B10.QBR (K(b), I(b), D(q) Qa-1/Tla(b)) anti-B10.MBR (K(b), I(k), D(q), Qa/Tla(a)) CTL line. These CTL lysed blasts from all Qa-1a strains regardless of the H-2 haplotype, indicating that the recognition of the Qa-1 antigen by these CTL is not restricted by other class I molecules. In bulk populations, CTL activity of this specificity was found only in the CD8+CD4- subpopulation. Accordingly, all established CTL clones were phenotyped as Thy-1+, CD8+CD4-. Furthermore, these clones were shown to express alpha-beta-TcR rather than gamma-delta-TcR. Thus, the results indicate that Qa-1 antigen can be recognized by alpha-beta-TcR T cells in a manner similar to recognition of classical class I molecules. C1 NCI,IMMUNOL BRANCH,BETHESDA,MD 20892. NR 15 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD DEC PY 1991 VL 74 IS 4 BP 578 EP 582 PG 5 WC Immunology SC Immunology GA GV393 UT WOS:A1991GV39300003 PM 1838350 ER PT J AU FUKAMACHI, H MCLACHLAN, JA AF FUKAMACHI, H MCLACHLAN, JA TI PROLIFERATION AND DIFFERENTIATION OF MOUSE UTERINE EPITHELIAL-CELLS IN PRIMARY SERUM-FREE CULTURE - ESTRADIOL-17-BETA SUPPRESSES UTERINE EPITHELIAL PROLIFERATION CULTURED ON A BASEMENT MEMBRANE-LIKE SUBSTRATUM SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY LA English DT Article DE UTERINE EPITHELIAL CELLS; MOUSE; TISSUE CULTURE; ESTRADIOL-17-BETA; ESTROGEN; EXTRACELLULAR MATRIX ID GROWTH-FACTOR; ESTROGEN; INVITRO; UTERUS; EXPRESSION; STROMA AB The effects of different substrata and estradiol-17-beta (E2) on proliferation and differentiation of mouse uterine epithelial cells was examined in a serum-free primary culture system. When cultured on rat-tail collagen gels, the epithelial cells rapidly increased in number to form a simple squamous cell layer that exhibited a relatively undifferentiated state (a few short microvilli, no secretory granules, and poorly developed endoplasmic reticulum). Addition of E2 into the culture medium did not affect the proliferation of epithelial cells on collagen gel. Uterine epithelial cells grown on a reconstituted basement membrane-like substratum (Matrigel) formed a simple columnar/cuboidal cell layer exhibiting fully developed characteristics (many long microvilli, many secretory granules, and fully developed endoplasmic reticulum). Examination of epithelial proliferation by counting substratum-attached cell number revealed only a slow increase in cell growth on Matrigel, and E2 did not significantly affect it. However, measurement of proliferating cells by labeling cells with 5-bromo-2'-deoxyuridine revealed that cells on Matrigel were replicating and that E2 (10(-7) to 10(-11) M) actually significantly suppressed epithelial proliferation. However, there was not an effect of E2 on total cell number, indicating that the cells in control medium replicate faster and detach more readily from the substratum than those in E2-supplemented medium on Matrigel. Thus, it is probable that E2 significantly reduces the rate of cell detachment from the substratum, which may mimic the in vivo condition where significant decrease in apoptosis or cell death is induced by E2. C1 NIEHS,REPROD & DEV TOXICOL LAB,DEV ENDOCRINOL SECT,RES TRIANGLE PK,NC 27709. RP FUKAMACHI, H (reprint author), UNIV TOKYO,FAC SCI,INST ZOOL,7-3-1 HONGO,BUNKYO KU,TOKYO 113,JAPAN. NR 30 TC 16 Z9 16 U1 0 U2 0 PU SOC IN VITRO BIOLOGY PI COLUMBIA PA 8815 CENTRE PARK DR,STE 210, COLUMBIA, MD 21045 SN 0073-5655 J9 IN VITRO CELL DEV B PD DEC PY 1991 VL 27 IS 12 BP 907 EP 913 PG 7 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA GX749 UT WOS:A1991GX74900003 PM 1757395 ER PT J AU CHU, CY LIU, BK WATSON, D SZU, SS BRYLA, D SHILOACH, J SCHNEERSON, R ROBBINS, JB AF CHU, CY LIU, BK WATSON, D SZU, SS BRYLA, D SHILOACH, J SCHNEERSON, R ROBBINS, JB TI PREPARATION, CHARACTERIZATION, AND IMMUNOGENICITY OF CONJUGATES COMPOSED OF THE O-SPECIFIC POLYSACCHARIDE OF SHIGELLA-DYSENTERIAE TYPE-1 (SHIGA BACILLUS) BOUND TO TETANUS TOXOID SO INFECTION AND IMMUNITY LA English DT Article ID INFLUENZAE TYPE-B; ESCHERICHIA-COLI K-12; ANTIBODY-RESPONSE; CAPSULAR POLYSACCHARIDE; NEISSERIA-MENINGITIDIS; UNITED-STATES; PROTEIN; LIPOPOLYSACCHARIDE; ANTIGEN; SHIGELLA-DYSENTERIAE-1 AB The background for developing conjugate vaccines for shigellosis composed of the O-specific polysaccharide (O-SP) bound to a protein is described elsewhere (C. Y. Chu, R. Schneerson, and J. B. Robbins, submitted for publication). Briefly, there is direct evidence for type (lipopolysaccharide [LPS])-specific protection after infection with the wild type or with attenuated strains of shigellae. Prospective studies of Israeli armed forces recruits show a correlation between preexisting serum immunoglobulin G (IgG) LPS antibodies and resistance to shigellosis (D. Cohen, M. S. Green, C. Block, R. Slephon, and I. Ofek, J. Clin. Microbiol. 29:386-389, 1991). In order to elicit IgG LPS-specific antibodies to Shigella dysenteriae type 1, the O-SP of this pathogen was purified and bound to tetanus toxoid (TT) by three schemes. The most immunogenic used a modification of a published method (C. Y. Chu, R. Schneerson, J. B. Robbins, and S. C. Rastogi, Infect. Immun. 40:245-256, 1983). The resultant O-SP-TT conjugates were stable and elicited high levels of IgG O-SP antibodies and booster responses in young mice when injected subcutaneously in saline at 1/10 the proposed human dose. Adsorption onto alum or concurrent administration with monophosphoryl lipid A enhanced both the IgG and IgM antibody responses to the O-SP of the conjugate; both the nonadsorbed and adsorbed conjugates elicited higher rises of IgG than of IgM antibodies. Clinical evaluations of S. dysenteriae type 1 O-SP-TT conjugates are planned. C1 NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892. NICHHD,BIOMETRY & MATH STAT BRANCH,BETHESDA,MD 20892. NIDDKD,CELLULAR & MOLEC BIOL LAB,BIOTECHNOL UNIT,BETHESDA,MD 20892. NR 67 TC 75 Z9 77 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 DEC PY 1991 VL 59 IS 12 BP 4450 EP 4458 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA GR214 UT WOS:A1991GR21400023 PM 1937803 ER PT J AU ROBRISH, SA OLIVER, C THOMPSON, J AF ROBRISH, SA OLIVER, C THOMPSON, J TI SUGAR METABOLISM BY FUSOBACTERIA - REGULATION OF TRANSPORT, PHOSPHORYLATION, AND POLYMER FORMATION BY FUSOBACTERIUM-MORTIFERUM ATCC-25557 SO INFECTION AND IMMUNITY LA English DT Article ID CHEMICALLY DEFINED MEDIUM; NUCLEATUM ATCC 10953; YOUNG-ADULT HUMANS; GLUCOSE-UTILIZATION; ANAEROBIC-BACTERIA; AMINO-ACIDS; DEGRADATION; CELLS; PERIODONTITIS; ATCC-10953 AB Strains of eight Fusobacterium species differed in the ability to use sugars as energy sources for growth. For Fusobacterium russii ATCC 25533, F. gonidiaformans ATCC 25563, and F. nucleatum ATCC 10953 (except for frutose), growth was marginal to poor on all of the sugars tested. Other species displayed reasonable growth on glucose, fructose, mannose, and galactose, and two strains of F. mortiferum (ATCC 25557 and ATCC 9817) grew well on six of the sugars tested, including sucrose and maltose. Glucose transport by resting cells of most of the species was dependent upon (or markedly stimulated by) the presence of a fermentable amino acid. By contrast, F. mortiferum cells rapidly accumulated glucose and other sugars in the absence of amino acids. Although these cells were constitutive for glucose uptake, accumulation of other sugars was specifically induced by growth of F. mortiferum on the appropriate sugar. Spectrophotometric analyses and in situ staining of anionic polyacrylamide gels showed that glucose and fructose (mannose) are phosphorylated by separate ATP-dependent kinases. Fructokinase was stable in air at 4-degrees-C, but under these conditions, > 70% of the glucokinase activity was lost. After overnight dialysis of the extract, no glucokinase activity was detectable; however, 65% of the initial enzyme activity was retained by inclusion of 1 mM dithiothreitol in the dialysis buffer. Thin-section electron microscopy showed that cells of F. mortiferum produced various amounts of intracellular glycogen during growth on the following sugars (in decreasing order of formation): galactose > sucrose > glucose > mannose > fructose. Mechanisms for sugar transport regulation, phosphorylation, and polymer synthesis by F. mortiferum cells are proposed. C1 NIDR,IMMUNOL LAB,CLIN IMMUNOL SECT,BETHESDA,MD 20892. RP ROBRISH, SA (reprint author), NIDR,MICROBIAL ECOL LAB,BETHESDA,MD 20892, USA. NR 42 TC 16 Z9 16 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 1991 VL 59 IS 12 BP 4547 EP 4554 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA GR214 UT WOS:A1991GR21400037 PM 1937813 ER PT J AU SZU, SC LI, XR STONE, AL ROBBINS, JB AF SZU, SC LI, XR STONE, AL ROBBINS, JB TI RELATION BETWEEN STRUCTURE AND IMMUNOLOGICAL PROPERTIES OF THE VI CAPSULAR POLYSACCHARIDE SO INFECTION AND IMMUNITY LA English DT Article ID HUMAN MONOCLONAL MACROGLOBULIN; ESCHERICHIA-COLI K1; TYPHOID-FEVER; NEISSERIA-MENINGITIDIS; SALMONELLA-TYPHI; ANTIGEN; IDENTIFICATION; PREVENTION; EPITOPE; VACCINE AB The Vi capsular polysaccharide of Salmonella typhi is a linear homopolymer of poly-alpha(1 --> 4)GalNAcp variably O acetylated at the C-3 position. Serum antibodies elicited by this antigen confer protective immunity against typhoid fever. The relation between the immunologic properties and structure of Vi was investigated by carboxyl reduction, O deacetylation, and acid hydrolysis. The immunogenicity of Vi was closely related to its degree of O acetylation. Partial O deacetylation slightly increased immunogenicity; complete O deacetylation eliminated the immunogenicity of Vi. O-deacetylated Vi, however, still reacted with antisera prepared by injection of whole bacteria. Carboxyl reduction, in contrast, had a comparatively slight effect upon both the immunogenicity and antigenicity of Vi. Retention levels of antigenicity after acid treatment were greater for both the native and carboxyl-reduced Vi than for the O-deacetylated product. The Courtauld-Koltun space-filling model of a pentamer of Vi demonstrated that the bulky nonpolar O-acetyls, which protrude in rows on both sides, make up most of the surface. The carboxyls are less exposed and are partially shielded by the O-acetyls. The molecular model thus provides an explanation for the dominant role of the O-acetyls, as well as the lesser effect of carboxyl reduction, upon the immunologic properties of Vi. C1 NIMH,INTRAMURAL RES PROGRAM,BETHESDA,MD 20892. RP SZU, SC (reprint author), NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892, USA. NR 33 TC 66 Z9 72 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 DEC PY 1991 VL 59 IS 12 BP 4555 EP 4561 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA GR214 UT WOS:A1991GR21400038 PM 1937814 ER PT J AU GEORGE, MS AF GEORGE, MS TI OBSESSIVE-COMPULSIVE DISORDER SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID GLUCOSE METABOLIC RATES; LA-TOURETTES SYNDROME; MAGNETIC-RESONANCE; FLUOXETINE; FLUVOXAMINE; CLOMIPRAMINE; SEROTONIN; SYMPTOMS; EXPOSURE; PATIENT AB Within the past decade the field of psychiatry has rediscovered the neuropsychiatric syndrome of obsessive-compulsive disorder (OCD). Although excellently described over 150 years ago, for many years OCD was thought to be rare, untreatable, and to arise from hidden psychodynamic conflicts. All of these earlier ideas now appear to be wrong. Occurring in approximately 2% of adults, OCD consists of recurrent intrusive thoughts (obsessions) or senseless repetitive actions (compulsions). Although the aetiology of OCD remains unclear, recent neuro-imaging studies implicate the basal ganglia and frontal conex as crucial structures in the pathogenesis of OCD. Genetic studies demonstrate a clear genetic component to OCD and an interesting link with chronic motor tics and the Gilles de la Tourette Syndrome. Although a true cure for the disorder remains elusive, most OCD symptoms respond well to treatment with 5HT reuptake inhibitors. The phenomenology and aetiology of OCD will be reviewed, with particular emphasis placed on the proper pharmacological treatment of this sometimes crippling disorder. RP GEORGE, MS (reprint author), NIMH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE RD,BETHESDA,MD 20892, USA. NR 75 TC 7 Z9 7 U1 3 U2 5 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0268-1315 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD DEC PY 1991 VL 6 SU 3 BP 57 EP 68 DI 10.1097/00004850-199112003-00006 PG 12 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA HF414 UT WOS:A1991HF41400006 PM 1806635 ER PT J AU POST, RM KETTER, TA JOFFE, RT KRAMLINGER, KL AF POST, RM KETTER, TA JOFFE, RT KRAMLINGER, KL TI LACK OF BENEFICIAL-EFFECTS OF L-BACLOFEN IN AFFECTIVE-DISORDER SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID GAMMA-AMINOBUTYRIC-ACID; HIPPOCAMPAL EPILEPTIFORM ACTIVITY; GABAB RECEPTORS; TRIGEMINAL NEURALGIA; ANTIDEPRESSANT DRUGS; PERTUSSIS TOXIN; CARBAMAZEPINE; HYPOTHESIS; NEURONS; BRAIN AB GABA(B) mechanisms have been implicated in the antinociceptive, but not anticonvulsant effects of carbamazepine. A variety of antidepressants have been reported to upregulate GABA(B) receptors after chronic administration. The GABA(B) agonist 1-baclofen was studied in depressed patients based on two separate rationales. 1-Baclofen, in doses ranging from 10-55 mg/day, was administered to five patients with primary affective disorder. No patient showed a positive clinical response, while three patients showed a pattern of increasing depression or cycling during treatment and improvement during withdrawal. These preliminary data suggest that GABA(B) agonism is unlikely to produce antidepressant effects and may be unrelated to the mechanism of carbamazepine's antidepressant action. These data, taken with a reinterpretation of other findings that antidepressant modalities upregulate GABA(B) receptors in brain following chronic administration, suggest that GABA(B) antagonism rather than agonism may be a fruitful clinical strategy to explore in depression. RP POST, RM (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,BETHESDA,MD 20892, USA. NR 55 TC 20 Z9 20 U1 1 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0268-1315 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD WIN PY 1991 VL 6 IS 4 BP 197 EP 207 DI 10.1097/00004850-199100640-00001 PG 11 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA HH688 UT WOS:A1991HH68800001 PM 1816278 ER PT J AU Roth, BJ Saypol, JM AF Roth, Bradley J. Saypol, Joshua M. TI THE FORMATION OF A RE-ENTRANT ACTION POTENTIAL WAVE FRONT IN TISSUE WITH UNEQUAL ANISOTROPY RATIOS SO INTERNATIONAL JOURNAL OF BIFURCATION AND CHAOS LA English DT Article AB In a syncytial tissue, the intracellular and extracellular spaces may have different degrees of anisotropy. This property allows generation of a re-entrant wave front in a two-dimensional sheet of tissue after two successive stimuli are applied through the same electrode, if the second stimulus is delivered during the vulnerable phase of the first action potential. The re-entrant wave front contains four phase singularities placed symmetrically about the position of the electrode. C1 [Roth, Bradley J.; Saypol, Joshua M.] NIH, Biomed Engn & Instrumentat Program, Bethesda, MD 20892 USA. RP Roth, BJ (reprint author), NIH, Bldg 13,Room 3W13, Bethesda, MD 20892 USA. NR 9 TC 10 Z9 10 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE SN 0218-1274 EI 1793-6551 J9 INT J BIFURCAT CHAOS JI Int. J. Bifurcation Chaos PD DEC PY 1991 VL 1 IS 4 BP 927 EP 928 DI 10.1142/S0218127491000671 PG 2 WC Mathematics, Interdisciplinary Applications; Multidisciplinary Sciences SC Mathematics; Science & Technology - Other Topics GA V44LO UT WOS:000209750700014 ER PT J AU LASSISE, DL SAVITZ, DA HAMMAN, RF BARON, AE BRINTON, LA LEVINES, RS AF LASSISE, DL SAVITZ, DA HAMMAN, RF BARON, AE BRINTON, LA LEVINES, RS TI INVASIVE CERVICAL-CANCER AND INTRAUTERINE-DEVICE USE SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article ID CONTRACEPTIVE DEVICES; MISCLASSIFICATION; RISK AB Although the hypothesis that intrauterine device (IUD) use might promote cervical cancer has been considered since the introduction of IUDs in the early 1900s, previous studies are inconclusive. Data collected in interviews with 481 invasive cervical cancer cases and 801 general population controls from Birmingham, Chicago, Denver, Miami and Philadelphia were used to address this issue. These data were analysed to determine the relationship between IUD use and the risk of cervical cancer, with consideration of the type of IUD (copper and inert) and duration of use. A nonsignificant reduced risk of cervical cancer was associated with copper IUD use, indicated by an adjusted odds ratio (OR) of 0.6 (95% Cl: 0.3-1.2), but virtually no effect was found for inert IUD use (OR = 1.1, 95% Cl: 0.9-1.7). Decreased risk with increased duration of copper IUD use supports a possible protective effect of copper IUD use on the development of invasive cervical cancer. C1 OUR LADY MERCY MED CTR,DEPT INTERNAL MED,COMMUNITY & PREVENT MED UNIT,BRONX,NY. UNIV COLORADO,HLTH SCI CTR,DEPT PREVENT MED & BIOMETR,DENVER,CO 80262. NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 32 TC 25 Z9 25 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD DEC PY 1991 VL 20 IS 4 BP 865 EP 870 DI 10.1093/ije/20.4.865 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GY323 UT WOS:A1991GY32300005 PM 1800424 ER PT J AU PARRISH, KM HIGUCHI, S MURAMATSU, T STINSON, FS HARFORD, TC AF PARRISH, KM HIGUCHI, S MURAMATSU, T STINSON, FS HARFORD, TC TI A METHOD FOR ESTIMATING ALCOHOL-RELATED LIVER-CIRRHOSIS MORTALITY IN JAPAN SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article AB In Japan, per capita alcohol consumption increased sharply during the post World War II period followed by an increase in cirrhosis mortality. The prevalence of alcoholic cirrhosis among hospitalized patients also increased, from 11% in 1969 to 18% in 1985. Despite an increase in the percentage of drinkers among young women, over 80% of women in Japan are still abstainers or light drinkers. Thus, female cirrhosis mortality rates can be used as a proxy measure of non-alcohol-related cirrhosis mortality rates to estimate alcohol-related cirrhosis deaths among Japanese men. Employing this method, we conclude that two-thirds of cirrhosis deaths among men between 24 and 85 years of age and half of all cirrhosis deaths were attributable to alcohol. Two factors are probably responsible for the differences in proportional morbidity and proportional mortality of alcohol-related cirrhosis: differences in survival rates between alcoholic and non-alcoholic cirrhosis patients and detection bias toward post-hepatic cirrhosis. The synergistic effect of alcohol on viral hepatitis may in part explain excess cirrhosis deaths among Japanese men. C1 CSR INC,ALCOHOL EPIDEMIOL DATA SYST,1400 EYE ST NW,WASHINGTON,DC 20005. NIAID,ROCKVILLE,MD 20857. KURIHAMA NATL HOSP,NATL INST ALCOHOLISM,YOKOSUKA,JAPAN. OI Makimoto, Kiyoko/0000-0003-0242-1290 NR 24 TC 6 Z9 6 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD DEC PY 1991 VL 20 IS 4 BP 921 EP 926 DI 10.1093/ije/20.4.921 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GY323 UT WOS:A1991GY32300013 PM 1800431 ER PT J AU PARAZZINI, F HILDESHEIM, A FERRARONI, M LAVECCHIA, C BRINTON, L AF PARAZZINI, F HILDESHEIM, A FERRARONI, M LAVECCHIA, C BRINTON, L TI RISK-FACTORS FOR CERVICAL-CANCER - COMMENTS ON ATTRIBUTABLE RISK CALCULATIONS AND THE EVALUATION OF SCREENING IN CASE-CONTROL STUDIES SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Letter ID DEFINITION C1 UNIV MILAN,IST BIOMETRIA & STAT MED,I-20122 MILAN,ITALY. NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. UNIV LAUSANNE,INST SOCIAL & PREVENT MED,CH-1005 LAUSANNE,SWITZERLAND. RP PARAZZINI, F (reprint author), MARIO NEGRI INST PHARMACOL RES,VIA ERITREA 62,I-20157 MILAN,ITALY. RI Brinton, Louise/G-7486-2015; Ferraroni, Monica/D-6548-2017; OI Brinton, Louise/0000-0003-3853-8562; Ferraroni, Monica/0000-0002-4542-4996; parazzini, fabio/0000-0001-5624-4854 NR 10 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 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD DEC PY 1991 VL 20 IS 4 BP 1142 EP 1143 DI 10.1093/ije/20.4.1142 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GY323 UT WOS:A1991GY32300047 ER PT J AU RUSSELL, IT WILCOX, AJ AF RUSSELL, IT WILCOX, AJ TI A CRITERION FOR LOW-BIRTH-WEIGHT SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Letter ID PERINATAL-MORTALITY; BIRTH-WEIGHT C1 NIEHS,DIV BIOMETRY & RISK ASSESSMENT,RES TRIANGLE PK,NC 27709. RP RUSSELL, IT (reprint author), UNIV ABERDEEN,HLTH SERV RES UNIT,ABERDEEN AB9 2ZD,SCOTLAND. RI Russell, Ian/H-1181-2012; OI Wilcox, Allen/0000-0002-3376-1311 NR 6 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD DEC PY 1991 VL 20 IS 4 BP 1145 EP 1145 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GY323 UT WOS:A1991GY32300049 PM 1800418 ER PT J AU NOMIZU, M INAGAKI, Y IWAMATSU, A KASHIWABARA, T OHTA, H MORITA, A NISHIKORI, K OTAKA, A FUJII, N ROLLER, PP AF NOMIZU, M INAGAKI, Y IWAMATSU, A KASHIWABARA, T OHTA, H MORITA, A NISHIKORI, K OTAKA, A FUJII, N ROLLER, PP TI SOLID-PHASE PEPTIDE-SYNTHESIS OF HUMAN ENDOTHELIN PRECURSOR PEPTIDES USING 2-STEP HARD ACID DEPROTECTION CLEAVAGE METHODS SO INTERNATIONAL JOURNAL OF PEPTIDE AND PROTEIN RESEARCH LA English DT Article DE CHYMOTRYPSIN CLEAVAGE; ENDOPROTEINASE ASP-N CLEAVAGE; FAB MASS SPECTROMETRY; PUTATIVE PRECURSOR OF HUMAN AND PORCINE ENDOTHELIN; SOLID PHASE PEPTIDE SYNTHESIS; TRIMETHYLSILYL BROMIDE DEPROTECTION; 2-STEP HARD ACID DEPROTECTION CLEAVAGE PROCEDURE ID VASOCONSTRICTOR PEPTIDE; PORCINE ENDOTHELIN; REAGENT AB Syntheses are described for the putative human and porcine biosynthetic precursors (hET-38 and pET-39) of endothelin, with the sequence previously deduced from human- and porcine-cDNA coding for preproendothelin. The Boc based solid phase synthetic method was applied, followed by weak hard acid, trimethylsilyl bromide, cleavage. The peptide removal from the resin was optimally accomplished with hydrogen fluoride. Disulfide bridges were formed by air-oxidation, and the linkage modes determined by enzymic (Endoproteinase Asp-N) digestion and HPLC. Five additional C-terminally elongated endothelin homologs were also synthesized. For alternative synthesis of pET-39, the use of trimethylsilyl trifluoromethanesulfonate for the removal of peptide from the resin generated a major side product, which was characterized. hET-38 was found to be less effective in vitro, when compared to endothelin. The vasoconstrictor activity in vitro of other related peptides was comparable to that of hET-38. C1 KIRIN BREWERY CO LTD,CENT LABS KEY TECHNOL,MAEBASHI,GUNMA,JAPAN. KIRIN BREWERY CO LTD,PHARMACEUT LAB,MAEBASHI,GUNMA,JAPAN. KYOTO UNIV,FAC PHARMACEUT SCI,KYOTO 606,JAPAN. RP NOMIZU, M (reprint author), NCI,MED CHEM LAB,BLDG 37,RM 5C02,BETHESDA,MD 20892, USA. NR 22 TC 9 Z9 9 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0367-8377 J9 INT J PEPT PROT RES JI Int. J. Pept. Protein Res. PD DEC PY 1991 VL 38 IS 6 BP 580 EP 587 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HB398 UT WOS:A1991HB39800012 PM 1819593 ER PT J AU NUSSENBLATT, RB AF NUSSENBLATT, RB TI EXPERIMENTAL AUTOIMMUNE UVEITIS - MECHANISMS OF DISEASE AND CLINICAL THERAPEUTIC INDICATIONS SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID LYMPHOCYTE-T CLONES; CELL LINES; S-ANTIGEN; UVEORETINITIS; RAT RP NUSSENBLATT, RB (reprint author), NEI, IMMUNOL LAB, NIH BLDG 10, ROOM 10N202, BETHESDA, MD 20892 USA. NR 40 TC 89 Z9 97 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD DEC PY 1991 VL 32 IS 13 BP 3131 EP 3141 PG 11 WC Ophthalmology SC Ophthalmology GA GV121 UT WOS:A1991GV12100003 PM 1748544 ER PT J AU GAREN, J FIELD, MJ KNELLER, G KARPLUS, M SMITH, J AF GAREN, J FIELD, MJ KNELLER, G KARPLUS, M SMITH, J TI TORSIONAL MOTIONS OF METHYL AND AMMONIUM GROUPS IN THE L-ALANINE CRYSTAL - A COMPARISON OF MOLECULAR-DYNAMICS AND NORMAL MODE CALCULATIONS SO JOURNAL DE CHIMIE PHYSIQUE ET DE PHYSICO-CHIMIE BIOLOGIQUE LA English DT Article; Proceedings Paper CT INTERNATIONAL SYMP ON ADVANCES IN BIOMOLECULAR SIMULATIONS CY MAR 12-14, 1991 CL OBERNAI, FRANCE SP IBM FRANCE, SOC FRANCAISE CHIM, DIV CHIM PHYS ID AMINO-ACIDS; RELAXATION AB The internal dynamics of L-alanine in the crystal environment were investigated using molecular dynamics simulations and normal mode calculations. Detailed results are presented for the rotational motion of the methyl and ammonium groups. The rotational barriers and librational frequencies are found to be significantly higher in the crystal than in the isolated molecule. Librational power spectra, calculated from the molecular dynamics simulations by Fourier transformation of the velocity autocorrelation function agree well with the forms and frequencies of the normal modes if the periodic box size used is large enough to avoid unphysical correlations. C1 CENS,DEPT BIOL CELLULAIRE & MOLEC,SERV BIOPHYS PROT & MEMBRANES,F-91190 GIF SUR YVETTE,FRANCE. IBM FRANCE,F-75012 PARIS,FRANCE. HARVARD UNIV,DEPT CHEM,CAMBRIDGE,MA 02138. RP GAREN, J (reprint author), NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892, USA. RI smith, jeremy/B-7287-2012 OI smith, jeremy/0000-0002-2978-3227 NR 18 TC 7 Z9 7 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0021-7689 J9 J CHIM PHYS PCB JI J. Chim. Phys.-Chim. Biol. PD DEC PY 1991 VL 88 IS 11-12 BP 2587 EP 2596 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Physical SC Biochemistry & Molecular Biology; Chemistry GA HD153 UT WOS:A1991HD15300027 ER PT J AU WEHR, TA GIESEN, HA SCHULZ, PM ANDERSON, JL JOSEPHVANDERPOOL, JR KELLY, K KASPER, S ROSENTHAL, NE AF WEHR, TA GIESEN, HA SCHULZ, PM ANDERSON, JL JOSEPHVANDERPOOL, JR KELLY, K KASPER, S ROSENTHAL, NE TI CONTRASTS BETWEEN SYMPTOMS OF SUMMER DEPRESSION AND WINTER DEPRESSION SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE SEASONAL AFFECTIVE DISORDER; ATYPICAL DEPRESSION; ENDOGENOUS DEPRESSION; APPETITE; WEIGHT; SLEEP ID SEASONAL AFFECTIVE-DISORDER; ATYPICAL DEPRESSION; CLASSIFICATION; HYPERSOMNIA; WEIGHT AB Epidemiological studies and studies of clinical populations suggest that there are primarily two opposite patterns of seasonally recurring depressions: summer depression and winter depression. In addition, there is preliminary evidence that the two seasonal types of depression may have opposite types of vegetative symptoms. In the present study, we prospectively monitored symptoms of depression in 30 patients with recurrent summer depression and 30 sex-matched patients with recurrent winter depression and compared the symptom profiles of the two groups. Consistent with predictions based on the earlier reports, we found that winter depressives were more likely to have atypical vegetative symptoms, with increased appetite, carbohydrate craving, weight gain and hypersomnia, and that summer depressives were more likely to have endogenous vegetative symptoms, with decreased appetite and insomnia. A cluster analysis performed on the patients' symptom profiles without reference to season of occurrence of their episodes separated 78% of the summer depressives and winter depressives from each other on the basis of their symptoms (chi-2 = 19.29, P < 0.001). RP WEHR, TA (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,BLDG 10,ROOM 4S-239,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 45 TC 41 Z9 43 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD DEC PY 1991 VL 23 IS 4 BP 173 EP 183 DI 10.1016/0165-0327(91)90098-D PG 11 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA GY358 UT WOS:A1991GY35800002 PM 1791262 ER PT J AU GAWIN, AZ EMERY, BE BARANIUK, JN KALINER, MA AF GAWIN, AZ EMERY, BE BARANIUK, JN KALINER, MA TI NASAL GLANDULAR SECRETORY RESPONSE TO CHOLINERGIC STIMULATION IN HUMANS AND GUINEA-PIGS SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE GUINEA PIG NASAL MUCOSA; NASAL SECRETION; METHACHOLINE; ATROPINE; GUINEA PIG ALBUMIN ID ALKALINE-PHOSPHATASE; PATHO-PHYSIOLOGY; HUMAN AIRWAYS; RHINITIS; SECRETIONS; INVITRO; MUCOSA AB A guinea pig model of nasal secretory responses was developed to assess the contributions of vascular permeability and glandular secretion responsible for the production of cholinergically stimulated nasal secretions. The nasal secretory responses to provocation with saline, methacholine, and atropine on the ipsilateral (challenged) side and contralateral (reflex) side were analyzed by measurement of total protein (Lowry method), guinea pig albumin (enzyme-linked immunosorbent assay), I-125-labeled bovine serum albumin after intravenous injection, and alkaline phosphatase enzyme activity in nasal fluid. Alkaline phosphatase was found to be localized to submucosal glands by zymography. Topical methacholine challenge increased the secretion of total protein, alkaline phosphatase activity, and albumin on the ipsilateral challenged side, whereas the percentage of total protein represented by albumin was not increased. This response was totally prevented by atropine pretreatment. Serial provocation with methacholine resulted in progressively reduced amounts of both the total protein and alkaline phosphatase in secretions. The observation that repeated challenges produced progressively smaller responses was also examined employing human nasal provocation. Repeating methacholine (25 mg) challenges four times at 10-min intervals in six human volunteers revealed that the initial challenge produced the largest response as reflected in total protein, albumin, lysozyme, lactoferrin, immunoglobulin (Ig) G, IgA, and secretory IgA secretion. When the constituents in secretions were analyzed in relationship to the total protein, the two vascular proteins, IgG and albumin, demonstrated the greatest decrements with repeated methacholine challenges. The glandular proteins, lactoferrin, lysozyme, and secretory IgA, either remained constant or increased in their relative proportion to total protein. Thus, cholinergic stimulation causes glandular secretion from both the guinea pig and human nasal mucosa. Repeated methacholine challenges resulted in progressively diminishing macromolecule secretion in guinea pigs and a depletion of plasma proteins in glandular secretions in humans. RP NIAID, CLIN INVEST LAB, BLDG 10, ROOM 11-C-209, BETHESDA, MD 20892 USA. NR 23 TC 30 Z9 30 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 EI 1522-1601 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD DEC PY 1991 VL 71 IS 6 BP 2460 EP 2468 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA GW105 UT WOS:A1991GW10500055 PM 1778947 ER PT J AU WEICKERT, MJ HOGG, RW ADHYA, S AF WEICKERT, MJ HOGG, RW ADHYA, S TI LOCATIONS AND ORIENTATIONS ON THE ESCHERICHIA-COLI PHYSICAL MAP OF THE MGL OPERON AND GALS, A NEW LOCUS FOR GALACTOSE ULTRAINDUCTION SO JOURNAL OF BACTERIOLOGY LA English DT Article C1 NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. CASE WESTERN RESERVE UNIV,SCH MED,DEPT MOLEC BIOL & MICROBIOL,CLEVELAND,OH 44160. NR 9 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 1991 VL 173 IS 23 BP 7412 EP 7413 PG 2 WC Microbiology SC Microbiology GA GR594 UT WOS:A1991GR59400005 PM 1938936 ER PT J AU HANSFORD, RG AF HANSFORD, RG TI DEHYDROGENASE ACTIVATION BY CA2+ IN CELLS AND TISSUES SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Review DE PYRUVATE DEHYDROGENASE; 2-OXOGLUTARATE DEHYDROGENASE; GLYCEROL 3-PHOSPHATE DEHYDROGENASE; INTRAMITOCHONDRIAL FREE CA2+; MITOCHONDRIAL CA2+ TRANSPORT; ADENINE NUCLEOTIDE PHOSPHORYLATION POTENTIAL ID RAT-HEART MITOCHONDRIA; ALPHA-KETOGLUTARATE DEHYDROGENASE; FREE CA-2+ CONCENTRATION; BROWN-ADIPOSE-TISSUE; CYTOSOLIC FREE CA-2+; ATPASE INHIBITOR PROTEIN; 4-BETA-PHORBOL 12-MYRISTATE 13-ACETATE; LINKED ISOCITRATE DEHYDROGENASE; NUCLEAR MAGNETIC-RESONANCE; MATRIX FREE CA-2+ AB The activation of intramitochondrial dehydrogenases by Ca2+ provides a link between the intensity of work performance by a tissue and the activity of pyruvate dehydrogenase and the tricarboxylate cycle, and hence the rate of ATP production by the mitochondria. Several aspects of this model of the control of oxidative phosphorylation are examined in this article, with particular emphasis on mitochondrial functioning in situ in cardiac myocytes and in the intact heart. Recent use of the fluorescent Ca2+ chelating agents indo-1 and fura-2 has allowed a more quantitative description of the dependence of dehydrogenase activity upon concentration of free intramitochondrial Ca2+, in experiments with isolated mitochondria. Further, a novel technique developed by Miyata et al. has allowed description of free intramitochondrial Ca2+ within a single cardiac myocyte, and the conclusion that this parameter changes in response to electrical excitation of the cell over a range which would be expected to give substantial modulation of dehydrogenase activity. RP HANSFORD, RG (reprint author), NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224, USA. NR 190 TC 115 Z9 116 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0145-479X J9 J BIOENERG BIOMEMBR JI J. Bioenerg. Biomembr. PD DEC PY 1991 VL 23 IS 6 BP 823 EP 854 DI 10.1007/BF00786004 PG 32 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA GV771 UT WOS:A1991GV77100001 PM 1778993 ER PT J AU STAFFORD, FJ BONIFACINO, JS AF STAFFORD, FJ BONIFACINO, JS TI A PERMEABILIZED CELL SYSTEM IDENTIFIES THE ENDOPLASMIC-RETICULUM AS A SITE OF PROTEIN-DEGRADATION SO JOURNAL OF CELL BIOLOGY LA English DT Article ID PRE-GOLGI COMPARTMENT; DEFECTIVE INTRACELLULAR-TRANSPORT; STEROL-ENHANCED DEGRADATION; ANTIGEN RECEPTOR CHAINS; MEMBRANE-BOUND DOMAIN; ABNORMAL PROTEINS; MOLECULAR-BASIS; ALPHA-SUBUNIT; HEAVY-CHAINS; MDCK CELLS AB Analysis of the fate of a variety of newly synthesized proteins in the secretory pathway has provided evidence for the existence of a novel protein degradation system distinct from that of the lysosome. Although current evidence suggests that proteins degraded by this system are localized to a pre-Golgi compartment before degradation, the site of proteolysis has not been determined. A permeabilized cell system was developed to examine whether degradation by this pathway required transport out of the ER, and to define the biochemical characteristics of this process. Studies were performed on fibroblast cell lines expressing proteins known to be sensitive substrates for this degradative process, such as the chimeric integral membrane proteins, Tac-TCR-alpha and Tac-TCR-beta. By immunofluorescence microscopy, these proteins were found to be localized to the ER. Treatment with cycloheximide resulted in the progressive disappearance of intracellular staining without change in the ER localization of the chimeric proteins. Cells permeabilized with the pore-forming toxin streptolysin O were able to degrade these newly synthesized proteins. The protein degradation seen in permeabilized cells was representative of that seen in intact cells, as judged by the similar speed of degradation, substrate selectivity, temperature dependence, and involvement of free sulfhydryl groups. Degradation of these proteins in permeabilized cells took place in the absence of transport between the ER and the Golgi system. Moreover, degradation occurred in the absence of added ATP or cytosol, and in the presence of apyrase, GTP-gamma-S, or EDTA; i.e., under conditions which prevent transport of proteins out of the ER. The efficiency and selectivity of degradation of newly synthesized proteins were also conserved in an isolated ER fraction. These data indicate that the machinery responsible for pre-Golgi degradation of newly synthesized proteins exists within the ER itself, and can operate independent of exogenously added ATP and cytosolic factors. RP STAFFORD, FJ (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 73 TC 86 Z9 86 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC PY 1991 VL 115 IS 5 BP 1225 EP 1236 DI 10.1083/jcb.115.5.1225 PG 12 WC Cell Biology SC Cell Biology GA GT488 UT WOS:A1991GT48800004 PM 1955470 ER EF