FN Thomson Reuters Web of Science™ VR 1.0 PT J AU LAUER, MS ANDERSON, KM LEVY, D AF LAUER, MS ANDERSON, KM LEVY, D TI INFLUENCE OF CONTEMPORARY VERSUS 30-YEAR BLOOD-PRESSURE LEVELS ON LEFT-VENTRICULAR MASS AND GEOMETRY - THE FRAMINGHAM HEART-STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID HYPERTROPHY; HYPERTENSION; ECHOCARDIOGRAPHY; DETERMINANT; POPULATION; CRITERIA; EXERCISE; DISEASE; STRESS; MEN AB To determine whether long-term blood pressure levels correlate with left ventricular mass, echocardiographic measurements were performed in 152 men and 299 women who were participants in the Framingham Heart Study. All subjects were free of obesity and cardiovascular and pulmonary disease, were not taking antihypertensive medications and had echocardiographic studies that were adequate for estimating left ventricular mass. Thirty-year average systolic blood pressure was correlated with left ventricular mass (corrected for height) (r = 0.27, p < 0.001 in men; r = 0.31, p < 0.001 in women). Multivariate linear regression analyses taking into account age and body mass index showed 30-year average systolic blood pressure to be a significant independent predictor of left ventricular mass (p < 0.01 in men and women). Systolic blood pressure at echocardiography was not independently associated with left ventricular mass when 30-year systolic blood pressure was entered into the multivariate model. The prevalence of left ventricular hypertrophy was associated with 30-year average systolic blood pressure (odds ratio for every 20-mm Hg increase in blood pressure: 3.20, p < 0.05 in men; 3.27, p < 0.001 in women). The increase in left ventricular mass associated with 30-year average systolic blood pressure reflected changes in left ventricular wall thickness but not in left ventricular internal dimension. Thirty-year average diastolic blood pressure was also correlated with left ventricular mass but to a lesser degree than was systolic blood pressure (r = 0.18, p < 0.05 in men; r = 0.18, p < 0.01 in women). It is concluded that long-term blood pressure levels are correlated with left ventricular mass and wall thickness but not with left ventricular internal dimension. Thirty-year average systolic blood pressure is a better predictor of left ventricular mass and wall thickness than is current rest blood pressure. Both current and long-term systolic blood pressures are better predictors of left ventricular mass and wall thickness than are current and long-term values for diastolic blood pressure. C1 NHLBI,FRAMINGHAM HEART STUDY,5 THURBER ST,FRAMINGHAM,MA 01701. CHARLES A DANA RES INST,BOSTON,MA. BETH ISRAEL HOSP,DEPT MED,DIV CARDIOVASC,HARVARD THORNDIKE LAB,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RI Lauer, Michael/L-9656-2013 OI Lauer, Michael/0000-0002-9217-8177 FU NHLBI NIH HHS [N01-HC-38038, HL07374] NR 31 TC 91 Z9 91 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 1 PY 1991 VL 18 IS 5 BP 1287 EP 1294 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA GM591 UT WOS:A1991GM59100017 PM 1833430 ER PT J AU FOX, PC AF FOX, PC TI SALIVA AND SALIVARY-GLAND ALTERATIONS IN HIV-INFECTION SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; AIDS-RELATED COMPLEX; PAROTID-GLAND; HTLV-III; VIRUS; MEN AB HIV-1 infection may involve saliva and the salivary glands. The virus may be recovered from the mouth and anti-viral antibodies are found in saliva. Salivary dysfunction after infection ranges from xerostomia to a Sjogren's syndrome-like condition with persistent glandular enlargement and marked secretory hypofunction. RP FOX, PC (reprint author), NIDR,CLIN INVEST SECT,BLDG 10,ROOM 1N-113,BETHESDA,MD 20892, USA. NR 24 TC 16 Z9 16 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD NOV PY 1991 VL 122 IS 12 BP 46 EP 48 PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA GP562 UT WOS:A1991GP56200012 PM 1686879 ER PT J AU RICHARDSON, L AF RICHARDSON, L TI ORAL-CANCER GROWTH-FACTOR FOUND SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article RP RICHARDSON, L (reprint author), NIDR,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD NOV PY 1991 VL 122 IS 12 BP 56 EP 56 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA GP562 UT WOS:A1991GP56200014 PM 1800543 ER PT J AU BURGIO, KL MATTHEWS, KA ENGEL, BT AF BURGIO, KL MATTHEWS, KA ENGEL, BT TI PREVALENCE, INCIDENCE AND CORRELATES OF URINARY-INCONTINENCE IN HEALTHY, MIDDLE-AGED WOMEN SO JOURNAL OF UROLOGY LA English DT Article DE URINARY INCONTINENCE; WOMEN ID NURSING-HOME PATIENTS; DYSFUNCTION; SEVERITY AB The prevalence, incidence and correlates of urinary incontinence were studied in a community-based sample of 541 healthy, middle-aged women 42 to 50 years old. Participants were evaluated on 2 occasions approximately 3 years apart. Of the participants 58% reported urine loss at some time and 30.7% reported incontinence on a regular basis at least once per month. During 3 years the cumulative incidence of regular incontinence in previously continent women was 8.0%. Among those with regular incontinence 64.9% said the volume of loss was 1 or 2 drops, while 35.1% reported that they needed to change their garments. Only 25.5% of the patients had sought treatment. Continence status was significantly related to body mass index and race but not to patient age, parity, caffeine or alcohol intake, smoking, physical activity, prior gynecological surgery or several psychological variables. The results indicate that urinary incontinence is common among middle-aged women. That few seek treatment suggests a need for more information about women's attitudes toward incontinence and more attention to this problem by health care providers. C1 UNIV PITTSBURGH,DEPT PSYCHIAT,PITTSBURGH,PA 15213. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RP BURGIO, KL (reprint author), UNIV PITTSBURGH,SCH MED,DEPT MED,GERIATR MED SECT,3520 5TH AVE,SUITE 300,PITTSBURGH,PA 15213, USA. FU NHLBI NIH HHS [HL28266]; NIA NIH HHS [K04 AG00431] NR 35 TC 285 Z9 293 U1 3 U2 10 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 1991 VL 146 IS 5 BP 1255 EP 1259 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA GM831 UT WOS:A1991GM83100014 PM 1942274 ER PT J AU PINCZOWSKI, D MCLAUGHLIN, JK LACKGREN, G ADAMI, HO PERSSON, I AF PINCZOWSKI, D MCLAUGHLIN, JK LACKGREN, G ADAMI, HO PERSSON, I TI OCCURRENCE OF TESTICULAR CANCER IN PATIENTS OPERATED ON FOR CRYPTORCHIDISM AND INGUINAL-HERNIA SO JOURNAL OF UROLOGY LA English DT Article DE CRYPTORCHIDISM; HERNIA, INGUINAL; CARCINOMA; TESTICULAR NEOPLASMS ID UNDESCENDED TESTIS; YOUNG MEN; MALIGNANCY; RISK AB We studied the incidence of testicular cancer in 2 population-based cohorts comprising 2,918 men who underwent an operation for a cryptorchid testis and 30,199 who underwent surgery for an inguinal hernia. Complete followup during the 19-year period was achieved by recored linkage to the National Swedish Cancer Registry. In the cryptorchidism cohort 4 cases of testicular cancer occurred versus 0.54 expected, yielding a relative risk of 7.4 (95% confidence interval 2.0 to 19.0). Of these patients 3 had undergone a bilateral operation due to intra-abdominal testes. There was no evidence of an association between inguinal hernia and risk of testicular cancer (relative risk = 1.1, 95% confidence interval 0.4 to 2.2). The validity of our data was further supported by relative risk estimates close to unity in a comparison group of appendectomy patients. We conclude that patients with a cryptorchid testis experience a substantially increased relative risk of testicular cancer. However, the low absolute risk, 4 cases during 25,360 person-years of observation, does not appear to justify special surveillance after an operation for an undescended testis. C1 UNIV HOSP UPPSALA,DEPT PEDIAT SURG,UPPSALA,SWEDEN. UNIV HOSP UPPSALA,DEPT GYNAECOL & OBSTET,UPPSALA,SWEDEN. NCI,BETHESDA,MD 20892. RP PINCZOWSKI, D (reprint author), UNIV HOSP UPPSALA,CANC EPIDEMIOL UNIT,UPPSALA,SWEDEN. NR 20 TC 59 Z9 61 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 1991 VL 146 IS 5 BP 1291 EP 1294 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA GM831 UT WOS:A1991GM83100022 PM 1682512 ER PT J AU FRICKHOFEN, N YOUNG, NS AF FRICKHOFEN, N YOUNG, NS TI A RAPID METHOD OF SAMPLE PREPARATION FOR DETECTION OF DNA VIRUSES IN HUMAN SERUM BY POLYMERASE CHAIN-REACTION SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE POLYMERASE CHAIN REACTION; OLIGONUCLEOTIDE; PARVOVIRIDAE; HEPATITIS-B VIRUS; CYTOMEGALOVIRUS ID PARVOVIRUS B19 DNA; NUCLEOTIDE-SEQUENCE; REACTION ASSAY; HEPATITIS; INFECTION; HIV-1; CELLS AB A rapid method of serum treatment is described that can be used for the detection of viral DNA by polymerase chain reaction (PCR). The key feature of the assay is inactivation of inhibitory serum factors by controlled heating of serum. This method avoids DNA extraction. It is very fast and limited sample handling decreases the chances of contamination by exogenous DNA. It has been successfully used for demonstration of parvovirus B19, hepatitis B virus, and human cytomegalovirus DNA in patient sera. Since pathological components in sera from patients with various diseases do not interfere in the assay, it can be used as a sensitive and safe screening assay for DNA viruses in a routine clinical setting. C1 NHLBI,CELL BIOL SECT,BETHESDA,MD 20892. NR 19 TC 39 Z9 41 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD NOV PY 1991 VL 35 IS 1 BP 65 EP 72 DI 10.1016/0166-0934(91)90086-F PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA GR411 UT WOS:A1991GR41100007 PM 1666114 ER PT J AU MALDARELLI, F MARTIN, MA STREBEL, K AF MALDARELLI, F MARTIN, MA STREBEL, K TI IDENTIFICATION OF POSTTRANSCRIPTIONALLY ACTIVE INHIBITORY SEQUENCES IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 RNA - NOVEL LEVEL OF GENE-REGULATION SO JOURNAL OF VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; VIRAL MESSENGER-RNA; TRANS-ACTIVATION; SPLICING EFFICIENCY; FUNCTIONAL-ANALYSIS; TARGET SEQUENCE; MAMMALIAN-CELLS; REV PROTEIN; EXPRESSION; HIV-1 AB cis-acting inhibitory region (IR) sequences were identified within the gag/pol gene of the human immunodeficiency virus type 1 (HIV-1) by using a novel feedback-stimulated, rev-independent tat reporter gene to screen HIV-1 sequences in transient expression assays. Two regions, a 1,295-nucleotide segment in the gag gene (IR-1) and a 1,932-nucleotide segment of the pol gene (IR-2), each inhibited reporter gene expression 10- to 20-fold. IR-1 and IR-2 both contained subsequences which inhibited reporter gene expression. Introduction of IR sequences into a heterologous reporter plasmid, pCMV-CAT, resulted in decreased chloramphenicol acetyltransferase expression, suggesting that the inhibitory effect was not restricted to a reporter gene under the control of the HIV-1 promoter. The presence of HIV IR sequences in cis did not alter relative levels of reporter gene RNA; however, fractionation studies revealed IR-containing RNA accumulated in the nucleus. These findings demonstrate that IR sequences within the gag/pol region affect gene expression by altering the cellular distribution of viral RNA. RP MALDARELLI, F (reprint author), NIAID, MOLEC MICROBIOL LAB, BETHESDA, MD 20892 USA. NR 53 TC 131 Z9 132 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD NOV PY 1991 VL 65 IS 11 BP 5732 EP 5743 PG 12 WC Virology SC Virology GA GL296 UT WOS:A1991GL29600009 PM 1656066 ER PT J AU CHESEBRO, B NISHIO, J PERRYMAN, S CANN, A OBRIEN, W CHEN, ISY WEHRLY, K AF CHESEBRO, B NISHIO, J PERRYMAN, S CANN, A OBRIEN, W CHEN, ISY WEHRLY, K TI IDENTIFICATION OF HUMAN-IMMUNODEFICIENCY-VIRUS ENVELOPE GENE-SEQUENCES INFLUENCING VIRAL ENTRY INTO CD4-POSITIVE HELA-CELLS, T-LEUKEMIA CELLS, AND MACROPHAGES SO JOURNAL OF VIROLOGY LA English DT Article ID CENTRAL NERVOUS-SYSTEM; HUMAN GLIAL-CELLS; MONONUCLEAR PHAGOCYTES; HTLV-III; MURINE RETROVIRUSES; DRUG-ABUSERS; HUMAN-BRAIN; INFECTION; TYPE-1; TISSUE AB Infectious recombinant viruses were constructed from three molecularly cloned human immunodeficiency virus (HIV) strains varying in cell tropism. All recombinants showed a high infectivity titer on phytohemagglutinin-stimulated normal T lymphocytes. However, a 120-bp region of the envelope gene including the area of the V3 hypervariable loop was found to influence infectivity titer on both clone 1022 CD4-positive HeLa cells and CD4-positive CEM leukemia cells. Infectivity for macrophages was more complex. All viruses replicated in macrophages to a low level, but viral sequences both inside and outside the V3 loop region influenced the efficiency of replication. Two experiments showed that the mechanism of restriction of infection of 1022 cells by HIV strain JR-CSF was related to lack of virus entry. First, productive virus infection occurred after transfection of 1022 cells with viral plasmid DNA. Second, the nonpermissive HIV strain JR-CSF could infect 1022 cells when pseudotyped with the envelope of other retroviruses, including human T-cell leukemia virus type I (HTLV-I), HTLV-II, and amphotropic murine leukemia virus. These results demonstrate the possibility that unexpected cell types might be infected with HIV in human patients coinfected with HIV and HTLV-I or HTLV-II. C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. UNIV CALIF LOS ANGELES,SCH MED,DEPT MICROBIOL & IMMUNOL,LOS ANGELES,CA 90024. OI Cann, Alan/0000-0002-9014-3720 NR 54 TC 158 Z9 158 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1991 VL 65 IS 11 BP 5782 EP 5789 PG 8 WC Virology SC Virology GA GL296 UT WOS:A1991GL29600015 PM 1920616 ER PT J AU FURTH, PA BAKER, CC AF FURTH, PA BAKER, CC TI AN ELEMENT IN THE BOVINE PAPILLOMAVIRUS LATE 3' UNTRANSLATED REGION REDUCES POLYADENYLATED CYTOPLASMIC RNA LEVELS SO JOURNAL OF VIROLOGY LA English DT Article ID MESSENGER-RNA; MOUSE CELLS; SEQUENCES; TRANSCRIPTION; TYPE-1; SITE; CARCINOMA; UPSTREAM; COMPLEX; INVITRO AB Expression of the two bovine papillomavirus type 1 (BPV-1) late genes, L1 and L2, coding for the two capsid proteins, is limited to terminally differentiated keratinocytes in bovine fibropapillomas. This pattern of expression is determined both by the activity of the late promoter and by the inhibition of late region expression in less well differentiated cells. Inhibition of L1 and L2 mRNA production in nonpermissive cells must occur since the late region potentially could be transcribed from early region promoters. Nuclear runoff analysis of the late region has demonstrated that up to 95% of transcripts which are initiated in the early region in nonpermissive cells terminate within the late region upstream of the late polyadenylation site (C. C. Baker and J. Noe, J. Virol. 63:3529-3534, 1989). However, very few of the primary transcripts which include the late polyadenylation site are processed into mRNA. In this study, we have used expression vectors to characterize an inhibitory element active in nonpermissive cells which is located in the late 3' untranslated region (3'UTR). While the late polyadenylation site is functional in these cells, a 53-bp element in the late 3'UTR reduces levels of polyadenylated cytoplasmic RNA. This element inhibited chloramphenicol acetyltransferase (CAT) expression 6- to 10-fold when cloned in the sense orientation into the 3'UTR of a CAT expression vector. No block to expression was seen when the fragment was cloned immediately downstream of the poly(A) site, in an intron upstream of the CAT coding sequence, or in an antisense orientation in the 3'UTR. When the same fragment was deleted from a BPV-1 L1 expression vector, a sixfold increase in mRNA levels was seen. Actinomycin D chase experiments using BPV-1 L1 expression vectors indicated that the element does not destabilize cytoplasmic polyadenylated RNA. Therefore, the element must act before the mature mRNA reaches the cytoplasm. The data presented are consistent with effects on nuclear stability and/or inhibition of polyadenylation or nuclear transport. RP FURTH, PA (reprint author), NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892, USA. NR 32 TC 76 Z9 77 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1991 VL 65 IS 11 BP 5806 EP 5812 PG 7 WC Virology SC Virology GA GL296 UT WOS:A1991GL29600018 PM 1717710 ER PT J AU COHEN, JI KIEFF, E AF COHEN, JI KIEFF, E TI AN EPSTEIN-BARR-VIRUS NUCLEAR PROTEIN-2 DOMAIN ESSENTIAL FOR TRANSFORMATION IS A DIRECT TRANSCRIPTIONAL ACTIVATOR SO JOURNAL OF VIROLOGY LA English DT Article ID LATENT MEMBRANE-PROTEIN; MAMMARY-TUMOR VIRUS; DNA-BINDING; REGULATORY ELEMENT; MAMMALIAN-CELLS; LYMPHOCYTES-B; ANTIGEN-2; EXPRESSION; IMMORTALIZATION; PROMOTER AB Epstein-Barr virus nuclear protein 2 (EBNA-2) increases mRNA levels of specific viral and cellular genes through direct or indirect effects on upstream regulatory elements. The EBNA-2 domains essential for these effects have been partially defined and correlate with domains important for B-cell growth transformation. To determine whether EBNA-2 has a direct transcriptional activating domain, gene fusions between the DNA-binding domain of GAL4 and EBNA-2 were tested in CHO and B-lymphoma cells for the ability to activate transcription from target plasmids containing GAL4 recognition sites upstream of an adenovirus or murine mammary tumor virus promoter. In B-lymphoma cells, a 37-amino-acid EBNA-2 domain previously identified to be essential for transformation was nearly as strong a transcriptional activator as the activating domain of herpes simplex virus transinducing factor VP16. A quadradecapeptide had about 25% of the activating activity of the longer peptide. This first evidence that EBNA-2 directly activates transcription should facilitate the identification of nuclear factors with which EBNA-2 interacts in transactivation and transformation. C1 HARVARD UNIV,SCH MED,DEPT MED & MICROBIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MOLEC GENET,BOSTON,MA 02115. RP COHEN, JI (reprint author), NIH,CLIN INVEST LAB,MED VIROL SECT,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA47006] NR 39 TC 97 Z9 99 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1991 VL 65 IS 11 BP 5880 EP 5885 PG 6 WC Virology SC Virology GA GL296 UT WOS:A1991GL29600026 PM 1656076 ER PT J AU BLASCO, R MOSS, B AF BLASCO, R MOSS, B TI EXTRACELLULAR VACCINIA VIRUS FORMATION AND CELL-TO-CELL VIRUS TRANSMISSION ARE PREVENTED BY DELETION OF THE GENE ENCODING THE 37,000-DALTON OUTER ENVELOPE PROTEIN SO JOURNAL OF VIROLOGY LA English DT Article ID HEMAGGLUTININ; RELEASE; FUSION; DISSEMINATION; N1-ISONICOTINOYL-N2-3-METHYL-4-CHLOROBENZOYLHYDRAZINE; POLYPEPTIDE; BIOGENESIS; INHIBITION; MEMBRANES; ANTIGEN AB There are two types of infectious vaccinia virus particles: intracellular naked virions and extracellular enveloped virions (EEV). To determine the biological role of the enveloped form of vaccinia virus, we produced and characterized a mutant that is defective in EEV formation. The strategy involved replacement by homologous recombination of the gene F13L, encoding a 37,000-Da protein (VP37) that is specific for the outer envelope of EEV, with a selectable antibiotic resistance marker, the Escherichia coli gpt gene. Initial experiments, however, suggested that such a mutation was lethal or prevented plaque formation. By employing a protocol consisting of high-multiplicity passages of intracellular virus from the transfected cells and then limiting dilution cloning, we succeeded in isolating the desired mutant, which was defective in production of plaques and extracellular virus but made normal amounts of intracellular naked virions. Electron microscopic examination indicated that the mutant virus particles, unlike wild type, were neither wrapped with Golgi-derived membranes nor associated with the cell surface. The absence of VP37 did not prevent the transport of the viral hemagglutinin to the plasma membrane but nevertheless abrogated both low-pH- and antibody-mediated cell fusion. These results indicate that VP37 is required for EEV formation and also plays a critical role in the local cell-to-cell transmission of vaccinia virus, perhaps via enveloped virions attached to or released from the cell membrane. By contrast, a mutated virus with a deletion of the K4L open reading frame, which is a homolog of the VP37 gene, was not defective in formation of plaques or EEV. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. RI Blasco, Rafael/B-5829-2016 NR 33 TC 240 Z9 241 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1991 VL 65 IS 11 BP 5910 EP 5920 PG 11 WC Virology SC Virology GA GL296 UT WOS:A1991GL29600030 PM 1920620 ER PT J AU NAKHASI, HL CAO, XQ ROUAULT, TA LIU, TY AF NAKHASI, HL CAO, XQ ROUAULT, TA LIU, TY TI SPECIFIC BINDING OF HOST-CELL PROTEINS TO THE 3'-TERMINAL STEM-LOOP STRUCTURE OF RUBELLA-VIRUS NEGATIVE-STRAND RNA SO JOURNAL OF VIROLOGY LA English DT Article ID SUBGENOMIC MESSENGER-RNA; DEFECTIVE INTERFERING RNAS; SINDBIS VIRUS; NUCLEOTIDE-SEQUENCE; GENOME RNA; REGION; GLYCOPROTEIN-E1; MUTAGENESIS; EVOLUTION; GENES AB At the 5' end of the rubella virus genomic RNA, there are sequences that can form a potentially stable stem-loop (SL) structure. The complementary negative-strand equivalent of the 5'-end SL structure of positive-strand rubella virus RNA [5' (+) SL structure] is thought to serve as a promoter for the initiation of positive-strand synthesis. We screened the negative-strand equivalent of the 5' (+) SL structure (64 nucleotides) and the adjacent region of the negative-strand RNA for their ability to bind to host cell proteins. Specific binding to the 64-nucleotide-long potential SL structure of three cytosolic proteins with relative molecular masses of 97, 79, and 56 kDa was observed by UV-induced covalent cross-linking. There was a significant increase in the binding of the 97-kDa protein from cells upon infection with rubella virus. Altering the SL structure by deleting sequences in either one of the two potential loops abolished the binding interaction. The 56-kDa protein also appeared to bind specifically to an SL derived from the 3' end of positive-strand RNA. The 3'-terminal structure of rubella virus negative-strand RNA shared the same protein-binding activity with similar structures in alphaviruses, such as Sindbis virus and eastern equine encephalitis virus. A possible role for the host proteins in the replication of rubella virus and alphaviruses is discussed. C1 NIAID,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. RP NAKHASI, HL (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV BIOCHEM,BETHESDA,MD 20014, USA. NR 29 TC 47 Z9 47 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1991 VL 65 IS 11 BP 5961 EP 5967 PG 7 WC Virology SC Virology GA GL296 UT WOS:A1991GL29600036 PM 1920622 ER PT J AU WILSON, CA EIDEN, MV AF WILSON, CA EIDEN, MV TI VIRAL AND CELLULAR FACTORS GOVERNING HAMSTER-CELL INFECTION BY MURINE AND GIBBON APE LEUKEMIA VIRUSES SO JOURNAL OF VIROLOGY LA English DT Article ID HOST RANGE; GENE-TRANSFER; RECOMBINANT RETROVIRUS; MAMMALIAN-CELLS; EXPRESSION; PSEUDOTYPES; RECEPTOR; LINEAGE AB Hamster cells are resistant to infection by most retroviruses, including Moloney murine leukemia virus (MoMLV) and gibbon ape leukemia viruses (GaLVs). We have constructed MoMLV-GaLV hybrid virions to identify viral and cellular determinants responsible for the inability of GaLV and MoMLV to infect hamster cells. The substitution of MoMLV core components for GaLV core components circumvents the resistance of hamster cells to infection by GaLV, demonstrating that hamster cells have receptors for GaLV but are not efficiently infected by this primate retrovirus because of a postpenetration block. In contrast, hamster cells are apparently resistant to MoMLV infection because although they bear a receptor for MoMLV, the receptor is nonfunctional. Treatment of CHO K1 or BHK 21 hamster cells with the glycoslyation inhibitor tunicamycin allows the cells to be infected by MoMLV. The construction of MoMLV-GaLV hybrid virions that can efficiently infect resistant cells has allowed the identification of viral and cellular factors responsible for restricting infection of hamster cells by MoMLV and GaLV. C1 NIMH,CELL BIOL LAB,BLDG 36,ROOM 2D10,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 34 TC 75 Z9 75 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1991 VL 65 IS 11 BP 5975 EP 5982 PG 8 WC Virology SC Virology GA GL296 UT WOS:A1991GL29600038 PM 1717711 ER PT J AU BERKOWER, I MURPHY, D SMITH, CC SMITH, GE AF BERKOWER, I MURPHY, D SMITH, CC SMITH, GE TI A PREDOMINANT GROUP-SPECIFIC NEUTRALIZING EPITOPE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 MAPS TO RESIDUE-342 TO RESIDUE-511 OF THE ENVELOPE GLYCOPROTEIN-GP120 SO JOURNAL OF VIROLOGY LA English DT Article ID AIDS VIRUS; NUCLEOTIDE-SEQUENCE; SOLUBLE CD4; HTLV-III; MONOCLONAL-ANTIBODIES; GP120; HIV; INFECTIVITY; RETROVIRUS; IDENTIFICATION AB Recombinant native human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins gp160 and gp120 (residues 1 to 511) expressed in insect cells quantitatively adsorbed the group-specific neutralizing antibodies found in human sera. However, these antibodies were not adsorbed by envelope fragment 1 to 471 or 472 to 857 or by both fragments sequentially, even though together they add up to the full-length gp160 sequence. A hybrid envelope glycoprotein was constructed with residues 342 to 511 of the HIV-1 sequence and residues 1 to 399 of the simian immunodeficiency virus type 1 sequence to vary the HIV-1 sequence while preserving its conformation. This hybrid glycoprotein quantitatively adsorbed human neutralizing antibodies, while native simian immunodeficiency virus type 1 envelope glycoprotein did not. These results identify a new neutralizing epitope that depends on conformation and maps to residues 342 to 511 of gp120. It overlaps the extended CD4-binding site but is distinct from the V3 loop described previously (K. Javaherian et al., Proc. Natl. Acad. Sci. USA 86:6768-6772, 1989; J. R. Rusche et al., Proc. Natl. Acad. Sci. USA 85:3198-3202). Since it is conserved among diverse HIV-1 isolates, this new epitope may be a suitable target for future vaccine development. C1 MICROGENESYS INC,MERIDEN,CT 06450. RP BERKOWER, I (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV BIOCHEM & BIOPHYS,MOLEC IMMUNOL LAB,NIH CAMPUS,BETHESDA,MD 20892, USA. NR 47 TC 37 Z9 37 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1991 VL 65 IS 11 BP 5983 EP 5990 PG 8 WC Virology SC Virology GA GL296 UT WOS:A1991GL29600039 PM 1717712 ER PT J AU PALLADINO, G SCHERLE, PA GERHARD, W AF PALLADINO, G SCHERLE, PA GERHARD, W TI ACTIVITY OF CD4+ T-CELL CLONES OF TYPE-1 AND TYPE-2 IN GENERATION OF INFLUENZA VIRUS-SPECIFIC CYTOTOXIC RESPONSES INVITRO SO JOURNAL OF VIROLOGY LA English DT Article ID STIMULATORY FACTOR-I; CYTOLYTIC LYMPHOCYTES-T; MONOCLONAL-ANTIBODIES; HELPER-CELL; DIFFERENTIATION FACTOR; FUNCTIONAL-ANALYSIS; INTERLEUKIN-2; PROLIFERATION; REQUIREMENT; ANTIGEN AB The activity of distinct CD4+ T-helper cell (Th) clones in promoting secondary A/PR/8/34/Mt.S.(H1N1) (A/PR8) influenza virus-specific, class I-restricted cytotoxic T-lymphocyte (CTL) responses in vitro was examined. CD8+ T cells which had been purified by fluorescence-activated cell sorter from spleen cells of A/PR8-primed mice were used as responders. On their own, purified CD8+ T cells were unable to generate cytotoxic activity upon in vitro culture with A/PR8-infected stimulator cells. Significant cytotoxic activity was generated in cultures that were additionally supplemented with A/PR8-specific Th clones or cell-free supernatant from these clones. Although there were large differences among individual Th clones in this function, Th clones of type 1 (Th1) promoted, on average, significantly stronger cytotoxic responses than Th clones of type 2 (Th2). The differences in promotion of a cytotoxic response correlated with the amount of interleukin-2 (IL-2) or IL-4 secreted by individual Th clones. These two lymphokines accounted for the CTL-promoting activity of the respective Th clones, since addition of recombinant IL-2 (IL-2) or rIL-4 to Th-free cultures substituted fully for the respective Th clones. As observed with Th clones, rIL-2 was significantly more effective than rIL-4 in promoting a cytotoxic response. When used in combination, Th2 clones had an antagonistic effect on the generation of a CTL response by Th1 clones. This effect could be partially transferred with cell-free supernatant from activated Th2 clones and could be reversed by addition of excess rIL-2. Both consumption of IL-2 by Th2 and secretion of an inhibitory factor(s) appear to be involved in this phenomenon. C1 NCI,METAB BRANCH,BETHESDA,MD 20892. RP PALLADINO, G (reprint author), WISTAR INST,3601 SPRUCE ST,PHILADELPHIA,PA 19104, USA. FU NIAID NIH HHS [AI-13989] NR 48 TC 36 Z9 36 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1991 VL 65 IS 11 BP 6071 EP 6076 PG 6 WC Virology SC Virology GA GL296 UT WOS:A1991GL29600049 PM 1920626 ER PT J AU ZHANG, YF MOSS, B AF ZHANG, YF MOSS, B TI VACCINIA VIRUS MORPHOGENESIS IS INTERRUPTED WHEN EXPRESSION OF THE GENE ENCODING AN 11-KILODALTON PHOSPHORYLATED PROTEIN IS PREVENTED BY THE ESCHERICHIA-COLI LAC REPRESSOR SO JOURNAL OF VIROLOGY LA English DT Article ID DNA; PURIFICATION; BIOGENESIS; VIRIONS; IDENTIFICATION; POLYPEPTIDE; PRECURSORS; POXVIRUSES; RIFAMPICIN; SEPARATION AB A conditional lethal vaccinia virus mutant, which constitutively expresses the Escherichia coli lac repressor and has the lac operator controlling the F18R gene (the 18th open reading frame of the HindIII F fragment of the vaccinia virus strain WR genome) encoding an 11-kDa protein, was previously shown to be dependent on the inducer isopropyl-beta-D-thiogalactoside (IPTG) for replication (Y. Zhang and B. Moss, Proc. Natl. Acad. Sci. USA 88:1511-1515, 1991). Further studies indicated that the yield of infectious virus could be regulated by titration with IPTG and that virus production was arrested by IPTG removal at appropriate times. Under nonpermissive conditions, an 11-kDa protein reactive with antiserum raised to a previously described DNA-binding phosphoprotein (S. Y. Kao and W. R. Bauer, Virology 159:399-407, 1987) was not synthesized, indicating that the latter is the product of the F18R gene. In the absence of IPTG, replication of viral DNA and the subsequent resolution of concatemeric DNA molecules appeared normal. Omission of IPTG did not alter the kinetics of early and late viral protein synthesis, although the absence of the 11-kDa polypeptide was noted by labeling infected cells with [S-35]methionine or [P-32]phosphate. Pulse-chase experiments revealed that proteolytic processing of the major viral structural proteins, P4a and P4b, was inhibited under nonpermissive conditions, suggesting a block in virus maturation. Without addition of IPTG, the failure of virus particle formation was indicated by sucrose gradient centrifugation of infected cell lysates and by the absence of vaccinia virus-mediated pH-dependent cell fusion. Electron microscopic examination of infected cells revealed that immature virus particles, with aberrant internal structures, accumulated when synthesis of the 11-kDa DNA-binding protein was prevented. C1 NIAID,VIRAL DIS LAB,BLDG 4,ROOM 229,BETHESDA,MD 20892. NR 33 TC 56 Z9 57 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1991 VL 65 IS 11 BP 6101 EP 6110 PG 10 WC Virology SC Virology GA GL296 UT WOS:A1991GL29600053 PM 1920628 ER PT J AU ABRAMCZUK, JW KEARNSJONKER, M MONELLTORRENS, E WOHLENBERG, C NOTKINS, AL AF ABRAMCZUK, JW KEARNSJONKER, M MONELLTORRENS, E WOHLENBERG, C NOTKINS, AL TI TRANSGENIC MOUSE LINES THAT ARE IMMUNOLOGICALLY TOLERANT AND NONTOLERANT TO HERPES-SIMPLEX VIRUS GLYCOPROTEIN-D SO JOURNAL OF VIROLOGY LA English DT Article ID PANCREATIC BETA-CELLS; MICE; ANTIGEN; EXPRESSION; GENE AB A construct containing the gene for glycoprotein D of herpes simplex virus (HSV-gD), under the control of the simian virus 40 early promoter, was microinjected into single-cell embryos, and four transgenic mouse lines were established. Three were homozygous (lines 75, 111, and 113) and one was hemizygous (line 108) for the HSV-gD gene. Examination of sera revealed that only one of the lines (line 75) spontaneously produced antibody to HSV-gD. Immunization of the other three lines with vaccinia virus-HSV-gD showed that one of them (line 113) responded by making antibody to HSV-gD, whereas the other two (lines 108 and 111) appeared to be immunologically tolerant. Evidence that tolerance was not absolute was obtained by immunization with infectious HSV, which resulted in an antibody response to HSV-gD in some of the animals from line 111. Examination of organs for HSV-gD mRNA revealed transcripts in the tolerant line (line 108) and in the partially tolerant line (line 111), but not in the nontolerant line (line 113), suggesting that the development of immunological tolerance requires active expression of the HSV-gD gene. C1 NIDR,ORAL MED LAB,BETHESDA,MD 20892. NR 25 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1991 VL 65 IS 11 BP 6124 EP 6128 PG 5 WC Virology SC Virology GA GL296 UT WOS:A1991GL29600055 PM 1717714 ER PT J AU KIM, SY EVANS, LH MALIK, FG ROUSE, RV AF KIM, SY EVANS, LH MALIK, FG ROUSE, RV TI MACROPHAGES ARE THE 1ST THYMIC CELLS TO EXPRESS POLYTROPIC RETROVIRUS IN AKR MOUSE LEUKEMOGENESIS SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA VIRUSES; BONE-MARROW; MICE; EPITHELIUM; MULVS; MCF AB AKR mice spontaneously develop T-cell leukemias in the thymus late in the first year of life. These neoplasms arise following the appearance in the thymus of a recombinant retrovirus but can be prevented by thymectomy, indicating a role for both virus and elements of the thymic microenvironment in leukemogenesis. The intrathymic appearance of recombinant retrovirus was examined at ages leading up to leukemogenesis in order to identify and characterize the microenvironments in which the virus is first expressed. A stromal cell, the macrophage, was found to be the first thymic element to produce detectable levels of recombinant retrovirus, approximately 12 weeks before thymocytes. This observation provides a mechanism to reconcile viral leukemogenesis with the requirement for an intact thymus. Thus, a nonlymphoid cell, the macrophage, may play a critical role in the development of lymphoid neoplasia. C1 VET ADM MED CTR,DEPT PATHOL,STANFORD,CA 94305. NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. NR 22 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1991 VL 65 IS 11 BP 6238 EP 6241 PG 4 WC Virology SC Virology GA GL296 UT WOS:A1991GL29600068 PM 1920631 ER PT J AU WYATT, LS RODRIGUEZ, WJ BALACHANDRAN, N FRENKEL, N AF WYATT, LS RODRIGUEZ, WJ BALACHANDRAN, N FRENKEL, N TI HUMAN HERPESVIRUS-7 - ANTIGENIC PROPERTIES AND PREVALENCE IN CHILDREN AND ADULTS SO JOURNAL OF VIROLOGY LA English DT Article ID EXANTHEM SUBITUM; HEALTHY-INDIVIDUALS; T-CELLS; ANTIBODY; IDENTIFICATION; INFECTION; AGENT; HBLV AB The recent isolation of human herpesvirus 7 (HHV-7) from activated CD4+ T lymphocytes of a healthy individual raises questions regarding the prevalence of this virus in humans and its immunological relationship to previously characterized human herpesviruses. We report that HHV-7 is a ubiquitous virus which is immunologically distinct from the highly prevalent T-lymphotropic HHV-6. Thus, (i) only two of six monoclonal antibodies to HHV-6 cross-reacted with HHV-7-infected cells, (ii) Western immunoblot analyses of viral proteins revealed different patterns for HHV-6- and HHV-7-infected cells, (iii) tests of sequential serum samples from children revealed seroconversion to HHV-6 without concomitant seroconversion to HHV-7, and (iv) in some instances HHV-7 infection occurred in the presence of high titers of HHV-6 antibodies, suggesting the lack of apparent protection of children seropositive for HHV-6 against subsequent infection with HHV-7. On the basis of the analyses of sera from children and adults it can be concluded that HHV-7 is a prevalent human herpesvirus which, like other human herpesviruses, infects during childhood. The age of infection appears to be somewhat later than the very early age documented for HHV-6. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. CHILDRENS HOSP,NATL MED CTR,WASHINGTON,DC 20010. UNIV KANSAS,MED CTR,DEPT MICROBIOL,KANSAS CITY,KS 66103. GEORGE WASHINGTON UNIV,WASHINGTON,DC 20052. FU NCRR NIH HHS [507-RRO573]; NIAID NIH HHS [AI-30355, AI-24224] NR 21 TC 163 Z9 167 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1991 VL 65 IS 11 BP 6260 EP 6265 PG 6 WC Virology SC Virology GA GL296 UT WOS:A1991GL29600071 PM 1656093 ER PT J AU SZEBENI, J DIEFFENBACH, C WAHL, SM VENKATESHAN, CN YEH, A POPOVIC, M GARTNER, S WAHL, LM PETERFY, M FRIEDMAN, RM WEINSTEIN, JN AF SZEBENI, J DIEFFENBACH, C WAHL, SM VENKATESHAN, CN YEH, A POPOVIC, M GARTNER, S WAHL, LM PETERFY, M FRIEDMAN, RM WEINSTEIN, JN TI INDUCTION OF ALPHA INTERFERON BY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN HUMAN MONOCYTE-MACROPHAGE CULTURES SO JOURNAL OF VIROLOGY LA English DT Note ID CENTRIFUGAL ELUTRIATION CCE; MONONUCLEAR CELL SUBSETS; NECROSIS FACTOR-ALPHA; ENRICHED FRACTIONS; INFECTION; AIDS; PHAGOCYTES AB The induction of interferon (IFN) by human immunodeficiency virus type 1 (HIV-1) in primary, nonstimulated monocyte-macrophage cultures was studied. HIV-1 infection, as confirmed by p24 antigen levels in the cell supernatant, led to the production of alpha interferon (IFN-alpha) over 7 to 21 days following infection. In two of seven experiments, the IFN detected was acid labile. Coupled reverse transcription-polymerase chain reaction analysis confirmed the induction of IFN-alpha mRNA in cells of HIV-1-infected cultures. C1 NCI,BETHESDA,MD 20892. NIDR,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. NR 25 TC 50 Z9 50 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1991 VL 65 IS 11 BP 6362 EP 6364 PG 3 WC Virology SC Virology GA GL296 UT WOS:A1991GL29600090 PM 1920639 ER PT J AU SMITH, GH GALLAHAN, D ZWIEBEL, JA FREEMAN, SM BASSIN, RH CALLAHAN, R AF SMITH, GH GALLAHAN, D ZWIEBEL, JA FREEMAN, SM BASSIN, RH CALLAHAN, R TI LONG-TERM INVIVO EXPRESSION OF GENES INTRODUCED BY RETROVIRUS-MEDIATED TRANSFER INTO MAMMARY EPITHELIAL-CELLS SO JOURNAL OF VIROLOGY LA English DT Note ID LACZ-GENE; VECTORS; GALACTOSIDASE; IMPLANTATION; CULTURE; LINEAGE; GLAND AB Nonimmortalized mouse mammary epithelial cells expressing Escherichia coli beta-galactosidase from a murine amphotropic packaged retroviral vector were injected into the epithelium-divested mammary fat pads of syngeneic mice. Mammary glands formed from the injected mammary epithelial cells contained ductal and lobular cells, both of which expressed beta-galactosidase when examined in situ more than 12 months later. These results indicate that stable recombinant gene expression can be achieved in vivo in the mammary gland without altering the growth properties of normal mammary epithelium. C1 NCI,TUMOR IMMUNOL & BIOL,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,DIV HEMATOL,WASHINGTON,DC 20007. UNIV ROCHESTER,SCH MED,DEPT MED,DIV CLIN IMMUNOL,ROCHESTER,NY 14642. NR 30 TC 36 Z9 36 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1991 VL 65 IS 11 BP 6365 EP 6370 PG 6 WC Virology SC Virology GA GL296 UT WOS:A1991GL29600091 PM 1656102 ER PT J AU BELLANTONI, MF HARMAN, SM CULLINS, VE ENGELHARDT, SM BLACKMAN, MR AF BELLANTONI, MF HARMAN, SM CULLINS, VE ENGELHARDT, SM BLACKMAN, MR TI TRANSDERMAL ESTRADIOL WITH ORAL PROGESTIN - BIOLOGICAL AND CLINICAL EFFECTS IN YOUNGER AND OLDER POSTMENOPAUSAL WOMEN SO JOURNALS OF GERONTOLOGY LA English DT Article ID ESTROGEN REPLACEMENT THERAPY; CORONARY-ARTERY DISEASE; HORMONE REPLACEMENT; BONE LOSS; ELDERLY WOMEN; SERUM; RISK; 17-BETA-ESTRADIOL; OSTEOPOROSIS; TESTOSTERONE AB The purpose of this study was to compare the biochemical and clinical effects of transdermal estrogen replacement therapy (eERT) in younger and older postmenopausal women. We treated 15 younger (< 60 y) and 13 older (greater-than-or-equal-to 60 y) healthy postmenopausal women (45-72 y) with four successive 8-week regimens of tERT at doses of 0 to 150-mu-g/day, combined with cyclic oral medroxyprogesterone acetate (MPA). In both age groups, there were similar (p = .0001) dose-responsive increases in plasma estrogen levels and decreases in LH and FSH levels, although LH values were lower in older women both before and after tERT (p < .02). The addition of MPA further suppressed LH and, to a lesser extent, FSH in both younger and older women. The ratio of estrogenized to nonestrogenized vaginal cells increased with tERT (p < .007) in both age groups, but significant symptomatic improvement of vaginal irritation was noted only at the highest tERT dose. Adverse effects unrelated to age included short-term nausea in 4/28 women, and skin irritation at the patch sites in 20/28 women. Vaginal bleeding was of shorter duration, but breast tenderness was more common in older women. Further studies of long-tem tERT effects in elderly women are indicated. C1 NIA, GERONTOL RES CTR, CLIN PHYSIOL LAB, BALTIMORE, MD 21224 USA. FRANCIS SCOTT KEY MED CTR, DIV GERIATR MED & GERONTOL, BALTIMORE, MD USA. FRANCIS SCOTT KEY MED CTR, DIV ENDOCRINOL & METABOLISM, BALTIMORE, MD USA. FRANCIS SCOTT KEY MED CTR, DIV GYNECOL, BALTIMORE, MD USA. FRANCIS SCOTT KEY MED CTR, DIV NURSING, BALTIMORE, MD USA. JOHNS HOPKINS UNIV, SCH MED, BALTIMORE, MD 21205 USA. FU NCRR NIH HHS [M01 RR-02719] NR 36 TC 16 Z9 16 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD NOV PY 1991 VL 46 IS 6 BP M216 EP M222 PG 7 WC Gerontology SC Geriatrics & Gerontology GA GN524 UT WOS:A1991GN52400017 PM 1834727 ER PT J AU NAKATSUKASA, H EVARTS, RP HSIA, CC MARSDEN, E THORGEIRSSON, SS AF NAKATSUKASA, H EVARTS, RP HSIA, CC MARSDEN, E THORGEIRSSON, SS TI EXPRESSION OF TRANSFORMING GROWTH FACTOR-BETA-1 DURING CHEMICAL HEPATOCARCINOGENESIS IN THE RAT SO LABORATORY INVESTIGATION LA English DT Article DE PRENEOPLASTIC NODULE; HEPATOCELLULAR CARCINOMA; INSITU HYBRIDIZATION; DESMIN-POSITIVE PERISINUSOIDAL CELL ID LIVER EPITHELIAL-CELLS; FACTOR-BETA; MESSENGER-RNAS; TGF-BETA; PROLIFERATION; REGENERATION; TRANSCRIPTS; INHIBITION; RECEPTOR; FIBROSIS AB Cellular distribution of both transcripts and protein of transforming growth factor (TGF)-beta-1 was studied in preneoplastic nodules (6 cases) and primary hepatic carcinomas (16 hepatocellular carcinomas and 2 mixed tumors of hepatocellular carcinoma and cholangiocellular carcinoma) produced by Solt-Farber's protocol in rats using in situ hybridization and immunohistochemistry. The TGF-beta-1 transcripts were primarily observed in nonparenchymal cells, some of which were desmin-positive perisinusoidal cells, surrounding or within the preneoplastic nodules or carcinomas. The distribution of latent TGF-beta-1 protein was similar to the transcripts. However, mature TGF-beta-1, which was identified with CC-antibody, was only detected in nonparenchymal cells and connective tissue associated with carcinomas, but was not observed in preneoplastic nodules or in normal liver with the exception of the periportal space. There was no difference in TGF-beta-1 expression associated with tumor types or the differentiation status of primary hepatic carcinomas. The present study demonstrates that nonparenchymal cells, particularly desmin-positive perisinusoidal cells, are the principal source of TGF-beta-1 production during hepatocarcinogenesis. Furthermore, the data suggest that the close interaction between nonparenchymal cells and carcinoma cells may be necessary for the activation of latent TGF-beta-1. It is hypothesized that regulatory effects of TGF-beta-1 on growth of preneoplastic or carcinoma cells in the liver are exerted via paracrine mechanism. RP NAKATSUKASA, H (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BLDG 37,ROOM 3C28,BETHESDA,MD 20892, USA. NR 28 TC 30 Z9 32 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD NOV PY 1991 VL 65 IS 5 BP 511 EP 517 PG 7 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA GQ437 UT WOS:A1991GQ43700003 PM 1753701 ER PT J AU AXIOTIS, CA GUARCH, R MERINO, MJ LAPORTE, N NEUMANN, RD AF AXIOTIS, CA GUARCH, R MERINO, MJ LAPORTE, N NEUMANN, RD TI P-GLYCOPROTEIN EXPRESSION IS INCREASED IN HUMAN SECRETORY AND GESTATIONAL ENDOMETRIUM SO LABORATORY INVESTIGATION LA English DT Article DE MENSTRUAL CYCLE; PROGESTERONE RECEPTORS; PREGNANCY; MONOCLONAL ANTIBODIES; IMMUNOHISTOCHEMISTRY ID DIFFERENTIAL TRANSPORT-PROPERTIES; MDR GENE-PRODUCTS; MULTIDRUG-RESISTANCE; MONOCLONAL-ANTIBODIES; PROGESTERONE RECEPTORS; MENSTRUAL-CYCLE; TISSUES; UTERUS; LOCALIZATION; EPITHELIUM AB To determine the expression, distribution, and intracellular localization of the multi-drug resistance gene product P-glycoprotein (Pgp) in the human menstrual cycle and in early gestational endometrium, we retrospectively studied 36 endometrial samples utilizing 3 murine monoclonal antibodies (MAbs), MAb C219, MAb C494, and MAb JSB-1, which recognize spatially distinct cytoplasmic epitopes of Pgp. Formalin-fixed, paraffin-embedded endometrial samples obtained from 36 women of reproductive age with normal menstrual cycles were assigned morphologic menstrual dates: proliferative (N = 10), secretory, (N = 19), menstrual (N = 1), and gestational endometrium (N = 6). The cellular localization, staining intensity, and percentage of Pgp immunoreactive cells varied with the phase of the menstrual cycle. Early proliferative endometria revealed no Pgp immunoreactivity for all three MAbs. Mid-proliferative endometria showed weak immunostaining in less than 15% of the glandular epithelia. Late proliferative endometria showed a strong apical paranuclear/Golgi staining pattern. Early secretory endometria showed strong luminal membranous, subnuclear vacuolar membranous, and supranuclear vacuolar membranous immunostaining to all 3 MAbs in greater than 80% of the glandular epithelia. Apical paranuclear/ Golgi and membranous staining were present in nonvacuolated mid-secretory glands. Immunoreactivity diminished in the late secretory phase with mild to moderate staining in less than 35% of the endometrial glands. Menstrual endometria showed weak, focal staining. All gestational endometria showed marked cytoplasmic, membranous, and apical/Golgi immunostaining both in the hypersecretory (Arias-Stella) endometrial glands as well as in the decidua. In general, the intensity of MAb C494 immunostaining was weaker than that of MAb C219 or JSB-1. These results suggest the following: Pgp expression parallels that of nuclear progesterone receptor expression in the normal human endometrial cycle and early gestational endometrium; Pgp expression corresponds to rising plasma and tissue levels of progesterone as well as to morphologic changes in the endometrial glandular epithelium associated with the marked development of the secretory apparatus; Pgp expression is hormonally regulated and may be involved in uteroplacental transport of substrates important in the implantation process and in early embryo-endometrial interactions; and Pgp may be involved in the transport of progesterone across the uterine epithelium during pregnancy. C1 NCI,WARREN GRANT MAGNUSON CLIN CTR,PATHOL LAB,BETHESDA,MD 20892. NCI,WARREN GRANT MAGNUSON CLIN CTR,DEPT NUCL MED,OFF DIRECTOR,BETHESDA,MD 20892. NR 25 TC 45 Z9 45 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD NOV PY 1991 VL 65 IS 5 BP 577 EP 581 PG 5 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA GQ437 UT WOS:A1991GQ43700011 PM 1721668 ER PT J AU PESCE, CM STRIKER, LJ PETEN, E ELLIOT, SJ STRIKER, GE AF PESCE, CM STRIKER, LJ PETEN, E ELLIOT, SJ STRIKER, GE TI GLOMERULOSCLEROSIS AT BOTH EARLY AND LATE STAGES IS ASSOCIATED WITH INCREASED CELL TURNOVER IN MICE TRANSGENIC FOR GROWTH-HORMONE SO LABORATORY INVESTIGATION LA English DT Note DE AUTORADIOGRAPHY ID EXPERIMENTAL GLOMERULONEPHRITIS; GLOMERULAR HYPERTROPHY; RENAL ENLARGEMENT; FACTOR-I; PROLIFERATION; SCLEROSIS; LESIONS; SIZE; RAT AB The evolution of glomerulosclerosis consists of a progressive increase in mesangial matrix with gradual glomerular obliteration. The sclerotic process is thought to be irreversible and include a progressive loss of glomerular cells. To investigate this process, we selected mice transgenic for bovine growth hormone because they develop progressive glomerulosclerosis and renal failure. The sequence of histologic events in the growth hormone mice consists initially of an increase in the number of centrolobular glomerular cells, followed by an accumulation of extracellular matrix. This is accompanied by an increase in glomerular size which is disproportionate to the overall increment in kidney or body weight. The [H-3]thymidine labeling index of the cells of the glomerular tuft was assessed before the development of recognizable sclerosis and at a time when the sclerosis was far advanced. The labeling index was more than five-fold increased over controls at the early time point. Contrary to what was expected, the labeling index remained at the same high levels in densely sclerotic glomeruli at the late time point. In conclusion, increased cell turnover is a significant component of the sclerotic process both at the onset and in the late stages of this model. RP PESCE, CM (reprint author), NIDDKD,METAB DIS BRANCH,RENAL CELL BIOL SECT,BLDG 10,ROOM 3N110,BETHESDA,MD 20892, USA. NR 22 TC 106 Z9 106 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD NOV PY 1991 VL 65 IS 5 BP 601 EP 605 PG 5 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA GQ437 UT WOS:A1991GQ43700014 PM 1753707 ER PT J AU TURNER, R LEBIHAN, D MOONEN, CTW DESPRES, D FRANK, J AF TURNER, R LEBIHAN, D MOONEN, CTW DESPRES, D FRANK, J TI ECHO-PLANAR TIME COURSE MRI OF CAT BRAIN OXYGENATION CHANGES SO MAGNETIC RESONANCE IN MEDICINE LA English DT Note ID DIFFUSION; BLOOD C1 NIH,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NIH,CTR INVIVO NMR RES,BETHESDA,MD 20892. RP TURNER, R (reprint author), NIH,CARDIAC ENERGET LAB,BETHESDA,MD 20892, USA. RI Turner, Robert/C-1820-2008; Moonen, Chrit/K-4434-2016 OI Moonen, Chrit/0000-0001-5593-3121 NR 19 TC 292 Z9 296 U1 0 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD NOV PY 1991 VL 22 IS 1 BP 159 EP 166 DI 10.1002/mrm.1910220117 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA GN341 UT WOS:A1991GN34100016 PM 1798390 ER PT J AU MUNDLOS, S MEYER, R YAMADA, Y ZABEL, B AF MUNDLOS, S MEYER, R YAMADA, Y ZABEL, B TI DISTRIBUTION OF CARTILAGE PROTEOGLYCAN (AGGRECAN) CORE PROTEIN AND LINK PROTEIN GENE-EXPRESSION DURING HUMAN SKELETAL DEVELOPMENT SO MATRIX LA English DT Article DE AGGRECAN; CARTILAGE PROTEOGLYCAN; CORE PROTEIN; LINK PROTEIN; SKELETAL DEVELOPMENT ID CDNA CLONES; LONG BONES; CHONDROGENESIS; LOCALIZATION; MECHANISM; GROWTH; ACID AB The distribution of cartilage proteoglycan core protein (aggrecan) and cartilage proteoglycan link protein was investigated by in situ hybridization during different stages of human skeletal development. Aggrecan and link protein expression were confined to chondrocytes of the developing skeleton and other cartilaginous structures. Distribution and intensity of the signal was identical with aggrecan as compared to link protein probes. Parallel to the calcification of cartilaginous matrix, chondrocytes of this area lost the expression of aggrecan and link protein specific mRNA and stayed negative throughout the following stages of skeletal development. Highest expression was found in the lower proliferative and upper hypertrophic zone whereas the resting zone showed less expression. Aggrecan gene expression was additionally investigated in iliac crest biopsies of 3 patients with pseudoachondroplasia and compared to age-matched controls. Distribution and intensity of staining revealed no abnormalities. Thus, the phenotypic changes during chondrocyte maturation are accompanied by distinct changes in aggrecan and link protein gene expression. This pattern was maintained in the growth plate of patients with pseudoachondroplasia. C1 UNIV MAINZ,DEPT PEDIAT,W-6500 MAINZ,GERMANY. NIH,DEV ANOMALIES LAB,BETHESDA,MD 20892. NR 21 TC 39 Z9 39 U1 0 U2 2 PU GUSTAV FISCHER VERLAG PI STUTTGART PA WOLLGRASWEG 49, D-70599 STUTTGART, GERMANY SN 0934-8832 J9 MATRIX JI Matrix PD NOV PY 1991 VL 11 IS 5 BP 339 EP 346 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GQ163 UT WOS:A1991GQ16300005 PM 1725805 ER PT J AU JOSEPHSON, JS AF JOSEPHSON, JS TI UPDATE ON DIAGNOSIS AND TREATMENT OF SINUS DISEASE - THE FUNCTIONAL ENDOSCOPIC SINUS SURGERY APPROACH SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID ACUTE MAXILLARY SINUSITIS; RECURRING RHINOSINUSITIS; INTRANASAL ETHMOIDECTOMY; ORBITAL COMPLICATIONS; ENDONASAL SURGERY; MANAGEMENT; CHILDREN C1 MAIMONIDES HOSP,DIV OTOLARYNGOL HEAD & NECK SURG,BROOKLYN,NY 11219. MAIMONIDES HOSP,CTR NASAL & SINUS,BROOKLYN,NY 11219. SUNY HLTH SCI CTR,DEPT OTOLARYNGOL HEAD & NECK SURG,BROOKLYN,NY. NIH,BETHESDA,MD 20892. NR 48 TC 4 Z9 4 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD NOV PY 1991 VL 75 IS 6 BP 1293 EP 1309 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA GQ727 UT WOS:A1991GQ72700008 PM 1943321 ER PT J AU LOVE, LA LEFF, RL FRASER, DD TARGOFF, IN DALAKAS, M PLOTZ, PH MILLER, FW AF LOVE, LA LEFF, RL FRASER, DD TARGOFF, IN DALAKAS, M PLOTZ, PH MILLER, FW TI A NEW APPROACH TO THE CLASSIFICATION OF IDIOPATHIC INFLAMMATORY MYOPATHY - MYOSITIS-SPECIFIC AUTOANTIBODIES DEFINE USEFUL HOMOGENEOUS PATIENT GROUPS SO MEDICINE LA English DT Article ID TRANSFER-RNA-SYNTHETASE; SYSTEMIC LUPUS-ERYTHEMATOSUS; SIGNAL-RECOGNITION PARTICLE; COMPUTER-ASSISTED ANALYSIS; INCLUSION BODY MYOSITIS; POLYMYOSITIS DERMATOMYOSITIS; SJOGRENS SYNDROME; ANTIBODY; DISEASE; ASSOCIATION C1 OKLAHOMA MED RES FDN,OKLAHOMA CITY,OK 73104. NINCDS,BETHESDA,MD 20892. RP LOVE, LA (reprint author), NIAMSD,BLDG 10,ROOM 9N228,BETHESDA,MD 20892, USA. OI Miller, Frederick/0000-0003-2831-9593 NR 61 TC 586 Z9 598 U1 0 U2 8 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD NOV PY 1991 VL 70 IS 6 BP 360 EP 374 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA GQ429 UT WOS:A1991GQ42900002 PM 1659647 ER PT J AU APLAN, PD LOMBARDI, DP KIRSCH, IR AF APLAN, PD LOMBARDI, DP KIRSCH, IR TI STRUCTURAL CHARACTERIZATION OF SIL, A GENE FREQUENTLY DISRUPTED IN T-CELL ACUTE LYMPHOBLASTIC-LEUKEMIA SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACTIVE-SITE TYROSINE; DNA TOPOISOMERASE-I; RECOMBINATION; SCL; TRANSLOCATIONS; SEQUENCES; LYMPHOMA; ENCODES; PROTEIN; REGION AB The SIL (SCL interrupting locus) gene was initially discovered at the site of a genomic rearrangement in a T-cell acute lymphoblastic leukemia cell line. This rearrangement, which occurs in a remarkably site-specific fashion, is present in the leukemic cells of 16 to 26% of patients with T-cell acute lymphoblastic leukemia. We have now cloned a normal SIL cDNA from a cell line which does not carry the rearrangement. The SIL cDNA has a long open reading frame of 1,287 amino acids, with a predicted molecular size of 143 kDa. The predicted protein is not homologous with any previously described protein; however, a potential eukaryotic topoisomerase I active site was identified. Cross-species hybridization using a SIL cDNA probe indicated that the SIL gene was conserved in mammals. A survey of human and murine cell lines and tissues demonstrated SIL mRNA to be ubiquitously expressed, at low levels, in hematopoietic cell lines and tissues. With the exception of 11.5-day-old mouse embryos, SIL mRNA was not detected in nonhematopoietic tissues. The genomic structure of SIL was also analyzed. The gene consists of 18 exons distributed over 70 kb, with the 5' portion of the gene demonstrating alternate exon utilization. C1 NCI,NAVAL MED BRANCH,BETHESDA,MD 20889. NCI,PEDIAT ONCOL BRANCH,BETHESDA,MD 20889. RI Aplan, Peter/K-9064-2016 NR 27 TC 86 Z9 89 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 1991 VL 11 IS 11 BP 5462 EP 5469 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GL382 UT WOS:A1991GL38200009 PM 1922059 ER PT J AU SUN, XH COPELAND, NG JENKINS, NA BALTIMORE, D AF SUN, XH COPELAND, NG JENKINS, NA BALTIMORE, D TI ID PROTEINS ID1 AND ID2 SELECTIVELY INHIBIT DNA-BINDING BY ONE CLASS OF HELIX-LOOP-HELIX PROTEINS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SCUTE GENE-COMPLEX; IMMUNOGLOBULIN ENHANCER; TRANSCRIPTION FACTOR; DROSOPHILA-MELANOGASTER; NEGATIVE REGULATOR; SEX DETERMINATION; MYC; DIFFERENTIATION; SEQUENCE; DOMAIN AB The DNA binding activities of some basic region and putative helix-loop-helix (bHLH)-containing transcriptional factors can be inhibited by the Id protein. Because Id contains the HLH motif for dimerization but not the basic amino acid region for DNA binding, heterodimers of Id with bHLH transcriptional factors may not bind to DNA. We have isolated and characterized the gene and cDNA clones for a new Id protein, designated Id2. The Id2 protein contains a helix-loop-helix motif similar to that of the previously described Id protein (referred to here as Id1), but the two proteins are different elsewhere. Id1 and Id2 are encoded by two unlinked genes, as shown by chromosome mapping. The two Id proteins have similar inhibitory activities. They selectively bind to and inhibit the function of one set of bHLH proteins, typified by E2A.E47 and E2B.m3, but not that of the other set, including TFE3, USF, and AP4. The Id proteins also homodimerize poorly. Expression of both Id genes is down-regulated during differentiation in a variety of cell types. C1 WHITEHEAD INST BIOMED RES,9 CAMBRIDGE CTR,CAMBRIDGE,MA 02142. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. ROCKEFELLER UNIV,NEW YORK,NY 10021. FU NCI NIH HHS [N01-CO-74101]; NIGMS NIH HHS [GM 39458] NR 47 TC 538 Z9 545 U1 0 U2 12 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 NOV PY 1991 VL 11 IS 11 BP 5603 EP 5611 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GL382 UT WOS:A1991GL38200025 PM 1922066 ER PT J AU OWENS, JD FINKELMAN, FD MOUNTZ, JD MUSHINSKI, JF AF OWENS, JD FINKELMAN, FD MOUNTZ, JD MUSHINSKI, JF TI NONHOMOLOGOUS RECOMBINATION AT SITES WITHIN THE MOUSE JH-C-DELTA LOCUS ACCOMPANIES C-MU DELETION AND SWITCH TO IMMUNOGLOBULIN-D SECRETION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HEAVY-CHAIN GENES; B-CELL LYMPHOMA; PLASMID DNA; HOMOLOGOUS RECOMBINATION; MESSENGER-RNA; NUCLEOTIDE-SEQUENCES; GEL-ELECTROPHORESIS; MAMMALIAN-CELLS; IGD-EXPRESSION; MYELOMA CELLS AB Plasma cells secrete immunoglobulins other than immunoglobulin M (IgM) after a deletion and recombination in which a portion of the immunoglobulin heavy-chain locus (IgH), from the 5'-flanking region of the mu constant-region gene (C-mu) to the 5'-flanking region of the secreted heavy-chain constant-region gene (C(H)), is deleted. The recombination step is believed to be targeted via switch regions, stretches of repetitive DNA which lie in the 5' flank of all C(H) genes except delta. Although serum levels of IgD are very low, particularly in the mouse, IgD-secreting plasmacytomas of BALB/c and C57BL/6 mice are known. In an earlier study of two BALB/c IgD-secreting hybridomas, we reported that both had deleted the C-mu gene, and we concluded that this deletion was common in the normal generation of IgD-secreting cells. To learn how such switch recombinations occur in the absence of a switch region upstream of the C-delta-1 exon, we isolated seven more BALB/c and two C57BL/6 IgD-secreting hybridomas. We determined the DNA sequences of the switch recombination junctions in eight of these hybridomas as well as that of the C57BL/6 hybridoma B1-8.delta-1 and of the BALB/c, IgD-secreting plasmacytoma TEPC 1033. All of the lines had deleted the C-mu gene, and three had deleted the C-delta-1 exon in the switch recombination event. The delta switch recombination junction sequences were similar to those of published productive switch recombinations occurring 5' to other heavy-chain genes, suggesting that nonhomologous, illegitimate recombination is utilized whenever the heavy-chain switch region is involved in recombination. C1 NCI,GENET LAB,BETHESDA,MD 20892. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. UNIFORMED SERV UNIV HLTH SCI,DEPT MED,BETHESDA,MD 20814. NR 74 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 NOV PY 1991 VL 11 IS 11 BP 5660 EP 5670 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GL382 UT WOS:A1991GL38200031 PM 1922069 ER PT J AU IACANGELO, AL GRIMES, M EIDEN, LE AF IACANGELO, AL GRIMES, M EIDEN, LE TI THE BOVINE CHROMOGRANIN A GENE - STRUCTURAL BASIS FOR HORMONE REGULATION AND GENERATION OF BIOLOGICALLY-ACTIVE PEPTIDES SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID RAT ADRENAL-MEDULLA; MESSENGER-RNA; MOLECULAR-CLONING; CHROMAFFIN CELLS; MAMMALIAN-CELLS; NERVOUS-TISSUE; PANCREASTATIN; ENDOCRINE; PROTEIN; SEQUENCE AB The structure of the gene encoding bovine chromogranin-A has been determined by characterization of two isolated genomic clones. Chromogranin-A is encoded by eight exons, which organize the coding region into several distinct structural and functional domains. Exons 1-5 represent the highly conserved signal peptide and N-terminal domain, which are separated into regions corresponding to the signal peptide, N-terminal sequence, disulfide-bonded loop, and remainder of the conserved N-terminal domain. Exon 6 represents the variable domain and encodes a region that is identical to the novel chromogranin-A-derived peptide chromostatin. Exon 7 encodes the biologically active peptide pancreastatin as well as most of the conserved C-terminal domain, with the remainder found on exon 8. The mRNA sequence obtained from the gene contains five nucleotide differences from the consensus sequence of four reported bovine chromogranin-A cDNA clones. Two of the differences in the gene result in two amino acid changes in the region encoded by exon 6. The structural organization of the chromogranin-A gene resembles that of the chromogranin-B gene in the exons corresponding to the signal peptide, N-terminal sequence, disulfide loop, and C-terminal sequence. Sequence analysis of the promoter region reveals the presence of a cAMP-responsive element located at 24 bases up-stream of the TATA box, a site positioned 125 bases from the cAMP-responsive element that is similar to the consensus sequence established for glucocorticoid-responsive elements, and two elements located further up-stream which each match six of seven bases of the AP-1-binding consensus sequence TGAG/CTCA, a heptanucleotide sequence in which the fourth base is G or C. Changes in chromogranin-A mRNA abundance after treatment with dexamethasone, forskolin, and phorbol ester indicate a potential role for all of these elements in the regulation of the chromogranin-A gene in endocrine cells. C1 UNIV CALIF SAN FRANCISCO,DEPT BIOCHEM & BIOPHYS,SAN FRANCISCO,CA 94143. RP IACANGELO, AL (reprint author), NIMH,CELL BIOL LAB,MOLEC & CELLULAR NEUROBIOL UNIT,BLDG 36,ROOM 3A17,BETHESDA,MD 20892, USA. OI Eiden, Lee/0000-0001-7524-944X NR 45 TC 59 Z9 60 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD NOV PY 1991 VL 5 IS 11 BP 1651 EP 1660 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GQ909 UT WOS:A1991GQ90900010 PM 1779968 ER PT J AU ADAMO, ML BENHUR, H ROBERTS, CT LEROITH, D AF ADAMO, ML BENHUR, H ROBERTS, CT LEROITH, D TI REGULATION OF START SITE USAGE IN THE LEADER EXONS OF THE RAT INSULIN-LIKE GROWTH FACTOR-I GENE BY DEVELOPMENT, FASTING, AND DIABETES SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID MESSENGER RIBONUCLEIC-ACIDS; IGF-I; TETRAMETHYLAMMONIUM CHLORIDE; 5'-UNTRANSLATED REGIONS; MOLECULAR-CLONING; EXPRESSION; SEQUENCE; RECEPTOR; HORMONE; RNAS AB Rat insulin-like growth factor-I (IGF-I) mRNAs with different 5'-untranslated region/prepeptide coding sequences result from transcription initiation in one of two leader exons. While not altering the mature IGF-I coding sequence, these different leaders potentially encode two distinct IGF-I prepeptides, one of 48 amino acids (exon 1) and one of 32 amino acids (exon 2). Within exon 1, transcription initiation is dispersed (i.e. occurs over a approximately 350-basepair region), while within exon 2, it is highly localized. A fourth exon 1 start site, residing only approximately 30 basepairs from its 3' end, is suggested on the basis of RNase protection assays; its use would produce an mRNA encoding a third distinct IGF-I leader peptide of 22 amino acids. We have determined that during postnatal development, and as a result of insulinopenic diabetes and fasting, choice of transcription start sites within exon 1 in the liver is coordinately regulated, i.e. use of all start sites increased during development and decreased in the two catabolic states. Transcription initiation at the single major site within exon 2 was also reduced in diabetes and fasting. Insulin replacement therapy and refeeding restored the levels of all transcripts coordinately. During postnatal development, however, transcripts initiating within exon 2 exhibited a different developmental profile than did exon 1 transcripts, increasing especially at the onset of GH-dependent linear growth. In liver, therefore, negative regulation of exon 1 and exon 2 transcription start site usage occurs in catabolic states, while in development, differential regulation of exon 1 and exon 2 transcription start sites occurs. RP ADAMO, ML (reprint author), NIDDKS,DIABET BRANCH,MOLEC & CELLULAR PHYSIOL SECT,BLDG 10,ROOM 8S-243,BETHESDA,MD 20892, USA. OI Roberts, Charles/0000-0003-1756-5772 NR 36 TC 123 Z9 123 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD NOV PY 1991 VL 5 IS 11 BP 1677 EP 1686 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GQ909 UT WOS:A1991GQ90900013 PM 1779970 ER PT J AU SGAGIAS, MK KASID, A DANFORTH, DN AF SGAGIAS, MK KASID, A DANFORTH, DN TI INTERLEUKIN-1-ALPHA AND TUMOR-NECROSIS-FACTOR-ALPHA (TNF ALPHA) INHIBIT GROWTH AND INDUCE TNF MESSENGER-RNA IN MCF-7 HUMAN BREAST-CANCER CELLS SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID CYTOMETRIC DNA ANALYSIS; RECOMBINANT INTERLEUKIN-1; MOLECULAR-CLONING; FACTOR EXPRESSION; CYTO-TOXICITY; PROLIFERATION; RESISTANCE; CACHECTIN; RECEPTOR; INVITRO AB We studied the effects of interleukin-1-alpha (IL-1) and tumor necrosis factor-alpha (TNF), alone and in combination, on MCF-7 breast cancer cells to determine whether these cytokines alter cell growth, TNF gene expression, and TNF secretion. We found that IL-1 alone and TNF alone inhibited cell growth in a dose-dependent manner. Each cytokine arrested growth in the G0/G1 phase of the cell cycle, with maximum growth inhibition at 1000 U/ml (P < 0.05) and 100 U/ml (P < 0.01), respectively. However, the combination of these two cytokines did not result in greater growth inhibition or a greater percentage of cells arrested in the G0/G1 phase of the cell cycle compared with each cytokine alone. We examined the effect of exogenous IL-1 and TNF on TNF gene expression by Northern blot analysis. In the absence of any cytokine, these cells do not express TNF mRNA. Exposure to IL-1 (1000 U/ml) induced TNF mRNA at 3 h; however, mRNA levels diminished thereafter to barely detectable levels by 24 h. Exposure to TNF (1000 U/ml) also induced TNF mRNA at 3 h, but in contrast to IL-1, the level of enhanced expression persisted at these levels through 72 h of exposure. Secretion of TNF by these cells is induced by exogenous TNF, but not by IL-1. IL-1 and TNF in combination do not produce greater inhibition of growth, greater amounts of TNF mRNA at 3 h, or greater secretion of TNF than that produced by TNF alone. These findings indicate that these two cytokines, while inhibiting cell growth, have different effects on TNF gene expression and secretion, suggesting different modes of action. In contrast to their actions on other cell types, these cytokines are not additive or synergistic in their effects on these breast cancer cells. The finding that TNF induces gene expression and secretion of TNF also indicates an important potential regulatory role of the cytokine on these cells. C1 NCI,SURG BRANCH,BLDG 10,ROOM 2B38,BETHESDA,MD 20892. NR 32 TC 34 Z9 34 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD NOV PY 1991 VL 5 IS 11 BP 1740 EP 1747 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GQ909 UT WOS:A1991GQ90900020 PM 1779975 ER PT J AU KUTA, AE BASHFORD, CL PASTERNAK, CA REYNOLDS, CW HENKART, PA AF KUTA, AE BASHFORD, CL PASTERNAK, CA REYNOLDS, CW HENKART, PA TI CHARACTERIZATION OF NON-LYTIC CYTOLYSIN MEMBRANE INTERMEDIATES SO MOLECULAR IMMUNOLOGY LA English DT Article ID PURIFIED CYTOPLASMIC GRANULES; RAT LGL TUMORS; LYMPHOCYTE TUMORS; CYTO-TOXICITY; MECHANISM; PERFORIN; PERMEABILITY; COMPLEMENT; INHIBITION AB In order to understand the nature of cytolysin-membrane interactions, the characteristics of stable, non-lytic cytolysin-target cell intermediates formed at low ionic strength, neutral pH, and at physiological ionic strength, pH 6.0, were examined. Protease treatment of cytolysin-RBC intermediates formed at low ionic strength inhibited subsequent hemolysis when the intermediates were exposed to physiological ionic strength and pH. Similarly, when such intermediates were treated with anti-granule and anti-cytolysin antibodies a significant dose-dependent inhibition of hemolysis was observed. These results suggested that in this non-lytic state the cytolysin molecule was exposed on the RBC surface. If low ionic strength or pH 6.0 generated intermediates were washed in 0.5 M NaCl, hemolytic activity was greatly reduced and cytolysin activity could be recovered from the medium. In addition to RBC, both murine (Yac-1 and Lettre ascites) and human (K562) tumor targets formed cytolysin-target cell intermediates at low ionic strength and at low pH. Multilamellar vesicles composed of either phosphatidylcholine, sphingomyelin or phosphatidylserine inhibited the binding of cytolysin to RBC at both low ionic strength and pH 6.0 indicating a lack of polar head group specificity for cytolysin binding. C1 ST GEORGE HOSP,SCH MED,DEPT CELLULAR & MOLEC SCI,LONDON SW17 0RE,ENGLAND. NCI,FREDERICK CANC RES FACIL,BIOL RESOURCES BRANCH,FREDERICK,MD 21701. RP KUTA, AE (reprint author), NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892, USA. NR 21 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD NOV PY 1991 VL 28 IS 11 BP 1263 EP 1270 DI 10.1016/0161-5890(91)90013-A PG 8 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA GQ732 UT WOS:A1991GQ73200013 PM 1961199 ER PT J AU EINHORN, GP QIN, L SOLOSKI, MJ AF EINHORN, GP QIN, L SOLOSKI, MJ TI BIOSYNTHESIS OF GLYCOPHOSPHOLIPID BOUND AND SECRETED MURINE CLASS-I QA-2 POLYPEPTIDES SO MOLECULAR IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; PHOSPHATIDYLINOSITOL MEMBRANE ANCHOR; CELL-SURFACE PROTEINS; GLYCOSYL-PHOSPHATIDYLINOSITOL; THY-1 GLYCOPROTEIN; TRANSPLANTATION ANTIGENS; GLYCOLIPID ANCHORS; GENE-EXPRESSION; PHOSPHOLIPASE-D; C57BL/10 MOUSE AB Murine T cells synthesize and express a cell-surface glycophospholipid anchored 40 kDa and a secreted water-soluble 39 kDa Qa-2 polypeptide. We have examined the biosynthetic pathways which lead to the production of the membrane-bound and water-soluble isoforms of the Qa-2 molecule. Using the detergent TX-114, both detergent (membrane)-bound and soluble Qa-2 polypeptides can be identified in cell lysates and can be distinguished by charge and molecular weight. Two membrane-bound forms, a 40-kDa Endo H resistant cell-surface form and a 38 kDa-Endo H sensitive form can be identified, both of which can be biosynthetically labeled with H-3-ethanolamine and can be converted to water soluble forms by digestion with a phosphatidylinositol specific phospholipase C. In addition, several water soluble polypeptides at 39, 37, 35 kDa, and a minor species at 33 kDa were identified, none of which radiolabel with H-3-ethanolamine. While the 39-kDa polypeptide was Endo H resistant, the other isoforms were sensitive to Endo H digestion. Pulse chase experiments and molecular weights of the deglycosylated core polypeptides suggest a precursor to product relationship between the intracellular water-soluble species and the mature 39-kDa secreted Qa-2 molecule. This relationship is supported by the observation that murine L cells transfected with the Qa-2 encoding class I gene Q7 fail to express membrane-bound Qa-2 molecules yet synthesize both intracellular water-soluble and secreted Qa-2 molecules. These findings argue for a pathway in which secreted soluble Qa-2 molecules are derived from intracellular precursors. C1 NIAID,BRB,BLDG 4,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV MOLEC & CLIN RHEUMATOL,BALTIMORE,MD 21205. FU PHS HHS [T32-07247, R01-20922] NR 50 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 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD NOV PY 1991 VL 28 IS 11 BP 1299 EP 1310 DI 10.1016/0161-5890(91)90017-E PG 12 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA GQ732 UT WOS:A1991GQ73200017 PM 1961202 ER PT J AU MOSS, J VAUGHAN, M AF MOSS, J VAUGHAN, M TI ACTIVATION OF CHOLERA-TOXIN AND ESCHERICHIA-COLI HEAT-LABILE ENTEROTOXINS BY ADP-RIBOSYLATION FACTORS, A FAMILY OF 20-KDA GUANINE NUCLEOTIDE-BINDING PROTEINS SO MOLECULAR MICROBIOLOGY LA English DT Review ID ADENYLATE-CYCLASE; RIBOSYLTRANSFERASE ACTIVITY; MESSENGER-RNA; ONCOGENE PROTEIN; RAS P21; GTP; MECHANISM; PSEUDOGENE; EXPRESSION; HYDROLYSIS AB Cholera toxin and Escherichia coli heat-labile enterotoxins are responsible, in part, for the symptomatology of cholera and traveller's diarrhoea, respectively. Effects of the toxins result from ADP-ribosylation of regulatory guanine nucleotide-binding (G) proteins; the ADP-ribosylated G protein is stabilized in an activated state, resulting in prolonged effects on its target. Toxin-catalysed ADP-ribosylation is stimulated in vitro by a family of guanine nucleotide-binding proteins, c. 20 kDa, termed ADP-ribosylation factors or ARFs. In the presence of GTP, but not GDP or adenine analogues, ARFs serve as allosteric activators of the toxin. The effects are amplified by certain phospholipids and detergents which promote guanine nucleotide binding. Six different mammalian ARF genes have been identified. They encode highly conserved, ubiquitous proteins of 175 to 181 amino acids, containing consensus domains responsible for guanine nucleotide binding. Differences in amino acid sequences are localized near the amino terminus and in the carboxy half of the protein. Although the physiological functions of ARFs have not been precisely defined, their immunological localization to the Golgi is consistent with a role in the regulated orderly movement of newly synthesized proteins from the endoplasmic reticulum, through the Golgi system to their ultimate destination. RP MOSS, J (reprint author), NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892, USA. NR 49 TC 27 Z9 28 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD NOV PY 1991 VL 5 IS 11 BP 2621 EP 2627 DI 10.1111/j.1365-2958.1991.tb01971.x PG 7 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA GT131 UT WOS:A1991GT13100008 PM 1779753 ER PT J AU GUSOVSKY, F AF GUSOVSKY, F TI PROSTAGLANDIN RECEPTORS IN NIH-3T3 CELLS - COUPLING OF ONE RECEPTOR TO ADENYLATE-CYCLASE AND OF A 2ND RECEPTOR TO PHOSPHOLIPASE-C SO MOLECULAR PHARMACOLOGY LA English DT Article ID ADRENAL CHROMAFFIN CELLS; INOSITOL 1,4,5-TRISPHOSPHATE; PHOSPHOINOSITIDE BREAKDOWN; PROLIFERATION; STIMULATION; HYDROLYSIS; FORSKOLIN; MEMBRANES; TURNOVER; RELEASE AB In intact NIH 3T3 murine fibroblasts, prostaglandins (PGs) F2-alpha and E2 induce dose-dependent stimulation of inositol monophosphate generation. PGF2-alpha is > 50-fold more potent than PGE2 in eliciting this response. In streptolysin O-permeabilized NIH 3T3 cells, PGF2-alpha and PGE2 induced dose-dependent accumulations of inositol bis- and trisphosphates, which were dependent on the presence of the guanine nucleotide guanosine-5'-O-(3-thio)triphosphate (GTP-gamma-S) (10-mu-M). Pretreatment of cells for 16 hr with 100 nm PGF2-alpha resulted in a significant reduction of not only subsequent PGF2-alpha- and PGE2-induced but also GTP-gamma-S-induced stimulation of inositol phosphate formation in permeabilized cells. PGF2-alpha-induced accumulation of inositol phosphates was partially inhibited by pretreatment with pertussis toxin (1-mu-g/ml, 4 hr). The inhibition by pertussis toxin was small but was not related to cyclic AMP formation, because forskolin, which activates adenylate cyclase, did not mimic pertussis toxin-induced inhibition. In the same cell line, PGF2-alpha and PGE2 induced a dose-dependent accumulation of cAMP and a dose-dependent potentiation of 0.5-mu-m forskolin-stimulated cAMP formation. PGF2-alpha and PGE2 were almost equipotent in eliciting both responses. However, PGF2-alpha was less efficacious than PGE2 and, in the presence of forskolin, PGF2-alpha at 10-mu-m induced an inhibitory effect on cAMP accumulation. Such inhibition may be related to PGF2-alpha-mediated phospholipase C activation and subsequent stimulation of protein kinase C, because the phorbol ester phorbol 12-myristate-13-acetate, which directly activates protein kinase C, also inhibited forskolin- and PGE2-induced cAMP accumulation. Pretreatment with PGF2-alpha for 16 hr did not reduce subsequent stimulation of cAMP accumulation by PGF2-alpha or PGE2. The results indicate that in NIH 3T3 cells two receptors for PGs are present, one that couples to adenylate cyclase, probably through G(s), and does not exhibit selectivity between PGF2-alpha and PGE2 and a second receptor that couples to phospholipase C through a guanine nucleotide-binding protein that is not sensitive to pertussis toxin pretreatment. The latter shows at least 40-fold selectivity towards PGF2-alpha over PGE2. Because long treatment with PGF2-alpha resulted in desensitization of the GTP-gamma-S-induced response, it is possible that long exposure to PGF2-alpha may down-regulate the guanine nucleotide-binding protein involved in phospholipase C signal transduction. RP GUSOVSKY, F (reprint author), NIDDKD,BIOORGAN CHEM LAB,BLDG 8,ROOM 1A-15,BETHESDA,MD 20892, USA. NR 24 TC 27 Z9 27 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 1991 VL 40 IS 5 BP 633 EP 638 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GQ445 UT WOS:A1991GQ44500005 PM 1658602 ER PT J AU RAMKUMAR, V OLAH, ME JACOBSON, KA STILES, GL AF RAMKUMAR, V OLAH, ME JACOBSON, KA STILES, GL TI DISTINCT PATHWAYS OF DESENSITIZATION OF ADENOSINE-A1 AND ADENOSINE-A2 RECEPTORS IN DDT1 MF-2 CELLS SO MOLECULAR PHARMACOLOGY LA English DT Article ID BETA-ADRENERGIC-RECEPTOR; A1 ADENOSINE RECEPTOR; ADENYLATE CYCLASE SYSTEM; SMOOTH-MUSCLE CELLS; DEPENDENT PROTEIN-KINASE; CYCLIC-AMP; HETEROLOGOUS DESENSITIZATION; ALPHA-1-ADRENERGIC RECEPTORS; BETA-2-ADRENERGIC RECEPTORS; GUANINE-NUCLEOTIDES AB Desensitization of adenosine receptors (ARs) was studied in DDT1 MF-2 cells, which possess both A1- and A2AR, differentially coupled to adenylate cyclase. (-)-N6-(R)-Phenylisopropyladenosine (R-PIA), an A1AR-selective agonist at the appropriate concentrations, desensitized A1AR-mediated inhibition of adenylate cyclase activity in a time- (t1/2, 8 hr) and dose-dependent and reversible fashion, This was associated with significant decreases in total A1AR number and in the number of receptors possessing a high affinity for agonist in membrane preparations. The decrease in total A1AR in the membranes from the desensitized cells (approximately 40%) was associated with a 37% increase in A1AR measured in light vesicle preparations, compared with control cells. To test a possible role of phosphorylation in A1AR desensitization, cells were incubated with [P-32]orthophosphate, followed by exposure to R-PIA for 18 hr. Subsequent purification of the A1AR indicated a 3-4-fold increase in phosphorylation of A1AR in cells treated with R-PIA, compared with control cells. Desensitization of the A1AR did not alter the levels of alpha-s and alpha-12 proteins or affect the ability of stimulatory effectors, such as isoproterenol, sodium fluoride, and forskolin, to activate adenylate cyclase. These results suggest that uncoupling, down-regulation, and phosphorylation of the A1AR contribute, at least in part, to desensitization of this inhibitory receptor. Desensitization of the A2AR was characterized using an A2-selective agonist, 2-[4-(2-{[4-aminophenyl]methylcarbonyl}ethyl)phenyl] ethylamino-5'-N-ethylcarboxamidoadenosine (PAPA-APEC). Pretreatment of cells with PAPA-APEC (100 nm) resulted in a rapid loss of agonist stimulation of adenylate cyclase activity (t1/2 of this effect, 45 min). This effect was dose dependent (EC50, approximately 10 nm) and rapidly reversible. Interestingly, desensitization of the A2AR resulted in no change in receptor number, affinity, or mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Taken together, these data suggest distinct mechanisms of desensitization of A1- and A2ARs in a single cell type. C1 DUKE UNIV,MED CTR,DEPT MED,BOX 3444,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT BIOCHEM,DURHAM,NC 27710. NIDDKD,CHEM & BIOORGAN CHEM LAB,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z99 DK999999, Z01 DK031117-20]; NHLBI NIH HHS [1F32-HL-07888-01, P50HL17670, R01HL35134] NR 36 TC 142 Z9 142 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 1991 VL 40 IS 5 BP 639 EP 647 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GQ445 UT WOS:A1991GQ44500006 PM 1944235 ER PT J AU LAWTON, MP KRONBACH, T JOHNSON, EF PHILPOT, RM AF LAWTON, MP KRONBACH, T JOHNSON, EF PHILPOT, RM TI PROPERTIES OF EXPRESSED AND NATIVE FLAVIN-CONTAINING MONOOXYGENASES - EVIDENCE OF MULTIPLE FORMS IN RABBIT LIVER AND LUNG SO MOLECULAR PHARMACOLOGY LA English DT Article ID SUBSTRATE-SPECIFICITY; OXIDATION-PRODUCTS; PULMONARY; DISTINCT; PROTEINS; MOUSE; PURIFICATION; ENZYMES; OXIDASE; GENES AB Our laboratory recently isolated and sequenced cDNAs encoding the microsomal flavin-containing monooxygenases (FMOs) from rabbit liver and rabbit lung. As a first step in understanding the molecular bases for the catalytic and physical differences between these enzymes, we have expressed them in COS-1 cells and compared the properties of the recombinant and native microsomal proteins. Microsomes from transfected cells were examined immunochemically by immunoblotting and catalytically by following methimazole oxidation in the presence and absence of various modulators. The expressed and native FMOs have the same mobilities in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the same responses to pH, sodium cholate, magnesium, and temperature, all of which serve to differentiate between the lung and liver enzymes. Analysis of methimazole metabolism in microsomes isolated from rabbit liver or lung showed biphasic kinetics, indicative of two or more enzymes taking part in the reaction. In contrast, the kinetics of methimazole oxidation catalyzed by the expressed FMOs were clearly linear and matched one of the phases observed with the native preparations. Chlorpromazine and imipramine, which are not substrates for the pulmonary FMO, were found to be competitive inhibitors of the high affinity reaction in pulmonary microsomes. These results, and others, indicate that both rabbit lung and liver contain more than one form of FMO. C1 NIEHS, CELLULAR & MOLEC PHARMACOL LAB, POB 12233, MD 19-08, RES TRIANGLE PK, NC 27709 USA. Scripps Res Inst, RES INST, DEPT MOLEC & EXPTL MED, DIV BIOCHEM, LA JOLLA, CA 92037 USA. NR 31 TC 36 Z9 36 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 1991 VL 40 IS 5 BP 692 EP 698 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GQ445 UT WOS:A1991GQ44500013 PM 1944240 ER PT J AU MENNITI, FS TAKEMURA, H OLIVER, KG PUTNEY, JW AF MENNITI, FS TAKEMURA, H OLIVER, KG PUTNEY, JW TI DIFFERENT MODES OF REGULATION FOR RECEPTORS ACTIVATING PHOSPHOLIPASE-C IN THE RAT PANCREATOMA CELL LINE-AR4-2J SO MOLECULAR PHARMACOLOGY LA English DT Article ID PROTEIN-KINASE-C; PAROTID ACINAR-CELLS; SUBSTANCE-P RECEPTOR; INOSITOL 1,4,5-TRISPHOSPHATE 3-KINASE; HOMOLOGOUS DESENSITIZATION; SIGNAL TRANSDUCTION; CALCIUM MOBILIZATION; GROWTH-FACTOR; CHICK HEART; AGONIST AB The inositol phosphate responses to substance P, bombesin, cholecystokinin, and the muscarinic cholinergic agonist methacholine were examined in the rat pancreatoma cell line AR4-2J. It was found that each agonist produced a distinct temporal pattern of inositol phosphate formation. Furthermore, these different response patterns resulted, at least in part, from different patterns of homologous receptor desensitization. The response to substance P desensitized rapidly and completely within 90 sec. After a 10-15-min refractory period, the response recovered with a t1/2 of approximately 1 hr. The response to methacholine also completely desensitized. However, in this case desensitization developed slowly over the course of 40 min, and no recovery of responsiveness was detected for up to 45 min after the cessation of stimulation. The inositol phosphate responses to bombesin and cholecystokinin were similar to one another and appeared to be composed of two phases. Initially, there was a robust activation of phospholipase C. This initial phase was followed within 20 sec by a second phase of lesser magnitude. For bombesin, attenuation of the initial phase was due to rapid, but only partial, desensitization of the response. Furthermore, the concentration of bombesin required to maintain the second phase of the response was about 100-fold lower than that required to maximally activate the initial phase of the response. These results may indicate multiple mechanisms for the regulation of different phospholipase C-linked receptors in this cell line. RP MENNITI, FS (reprint author), NIEHS,CELLULAR & MOLEC PHARMACOL SECT,CALCIUM REGULAT SECT,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Menniti, Frank/0000-0003-2612-9534 NR 47 TC 41 Z9 41 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 1991 VL 40 IS 5 BP 727 EP 733 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GQ445 UT WOS:A1991GQ44500018 PM 1719368 ER PT J AU CHAE, K GIBSON, MK KORACH, KS AF CHAE, K GIBSON, MK KORACH, KS TI ESTROGEN-RECEPTOR STEREOCHEMISTRY - LIGAND-BINDING ORIENTATION AND INFLUENCE ON BIOLOGICAL-ACTIVITY SO MOLECULAR PHARMACOLOGY LA English DT Article ID DIETHYLSTILBESTROL METABOLITES; MOLECULAR-STRUCTURES; MOUSE UTERUS; ANALOGS; ENANTIOMERS; SEPARATION; CYTOSOL; PROBES; ASSAY AB Racemic (Rac) 4'- and 5-deoxyindenestrol A (4'-DIA and 5-DIA), monohydroxyl analogs of the diethylstilbestrol (DES) oxidative metabolite indenestrol A (IA), were synthesized, and their enantiomers were resolved and isolated. Each compound was then tested for estrogen receptor (ER) binding affinity, uterotropic activity, and nuclear ER levels, to further define the stereochemical preference of the ER and to structurally evaluate the function of each IA hydroxyl group for binding and biological activity. Competitive binding to cytosolic ER determined the relative binding affinity of racemic mixtures of 4'- and 5-DIA as 1.3 and 3.7, respectively, compared with that of DES, 286. The ER exhibited a binding preference for the S-enantiomer of both compounds, with relative binding affinities of 4'-DIA-R, 0.2; 4'-DIA-S, 1.8; 5-DIA-R, 0.9; and 5-DIA S, 5.6. 4'-DIA-Rac produced 3 times the in vivo stimulation of 5-DIA-Rac in the uterotropic bioassay (with mouse uterine doubling doses of 302.4 and 800-mu-g/kg, respectively). Nuclear ER levels measured 1 hr after in vivo treatment with either 160-mu-g/kg 4'-DIA or 80-mu-g/kg 5-DIA showed a maximum binding level of 2 (4'-DIA) and 1.5 (5-DIA) times saline control, with these doses producing levels nearly equal to that caused by a 10-mu-g/kg dose of IA. Metabolic studies were carried out by treating mice with [H-3]4'- and [H-3]5-DIA-Rac, to determine the differential binding affinity and biological stimulation of 4'-DIA and 5-DIA. The in vivo metabolism of the [H-3]DIA compounds showed formation of [H-3]IA-Rac in urine extracts, as analyzed by chiral high performance liquid chromatography. Furthermore, in vitro incubation of unlabeled 4'- and 5-DIA-Rac with mouse liver microsomes showed stereospecific metabolism, with IA-S primarily formed from 4'-DIA-Rac and IA-R from 5-DIA-Rac. Metabolism of 4'-DIA-Rac to the more active IA S-enantiomer and of 5-DIA-Rac to the less active IA R-enantiomer contributes to the different biological activities, because the ER exhibits a chiral preference for these compounds. The higher binding affinity of 5-DIA indicates that the phenyl ring hydroxyl group is required for high affinity binding; however, both hydroxyl groups are needed for subsequent biological activity. These data further suggest that the ER demonstrates stereochemical ligand binding and that IA binds in an orientation relative to 17-beta-estradiol in which the IA phenyl ring corresponds to the estradiol A-ring. RP CHAE, K (reprint author), NIEHS,REPROD & DEV TOXICOL LAB,RECEPTOR BIOL SECT,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Korach, Kenneth/0000-0002-7765-418X NR 18 TC 17 Z9 17 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 1991 VL 40 IS 5 BP 806 EP 811 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GQ445 UT WOS:A1991GQ44500028 PM 1944245 ER PT J AU LIN, CM KANG, GJ ROACH, MC JIANG, JB HESSON, DP LUDUENA, RF HAMEL, E AF LIN, CM KANG, GJ ROACH, MC JIANG, JB HESSON, DP LUDUENA, RF HAMEL, E TI INVESTIGATION OF THE MECHANISM OF THE INTERACTION OF TUBULIN WITH DERIVATIVES OF 2-STYRYLQUINAZOLIN-4(3H)-ONE SO MOLECULAR PHARMACOLOGY LA English DT Article ID COLCHICINE-BINDING; ANTIMITOTIC AGENT; BRAIN BETA-1-TUBULIN; ALKYLATING-AGENTS; CROSS-LINKING; PODOPHYLLOTOXIN; ANALOGS; POLYMERIZATION; DRUGS; N,N'-ETHYLENEBIS(IODOACETAMIDE) AB A new class of antimitotic agents, derivatives of 2-styrylquinazolin-4(3H)-one (SQZ), was recently described [J. Med. Chem. 33:1721-1728 (1990)]. Because they appeared to interact at a new ligand binding site on tubulin, we attempted to determine their mechanism of action as inhibitors of tubulin polymerization. Although in initial studies inhibition of colchicine binding was negligible, substantial and competitive inhibition of this reaction could be demonstrated with very short incubation times (< 5 min), provided that a relatively low colchicine to tubulin ratio was used. The initial apparent failure to inhibit colchicine binding resulted from extremely rapid binding to tubulin and dissociation from tubulin by the SQZ derivatives, in comparison with the slow, temperature-dependent, poorly reversible binding of colchicine. The most inhibitory of the SQZ derivatives in the colchicine binding assay was 6-methyl-2-styrylquinazolin-4(3H)-one (NSC 379310), and its interaction with tubulin, particularly as an inhibitor of colchicine binding, was compared with that of 2-methoxy-5-(2',3',4'-trimethoxyphenyl)tropone (MTPT), because the binding parameters of MTPT with tubulin have been well described. The data indicate that NSC 379310 binds to tubulin and dissociates from the protein about 3 times as rapidly as MTPT. The other SQZ derivatives with equal or greater potency as inhibitors of tubulin polymerization but apparently less potency as inhibitors of colchicine binding presumably bind to and/or dissociate from tubulin even more rapidly than does NSC 379310. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,MOLEC PHARMACOL LAB,BLDG 37,BETHESDA,MD 20892. DUPONT CO,WILMINGTON,DE 19880. UNIV TEXAS,HLTH SCI CTR,DEPT BIOCHEM,SAN ANTONIO,TX 78284. NR 37 TC 31 Z9 32 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 1991 VL 40 IS 5 BP 827 EP 832 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GQ445 UT WOS:A1991GQ44500031 PM 1944246 ER PT J AU FISCHER, V HAAR, JA GREINER, L LLOYD, RV MASON, RP AF FISCHER, V HAAR, JA GREINER, L LLOYD, RV MASON, RP TI POSSIBLE ROLE OF FREE-RADICAL FORMATION IN CLOZAPINE (CLOZARIL)-INDUCED AGRANULOCYTOSIS SO MOLECULAR PHARMACOLOGY LA English DT Article ID ELECTRON-SPIN-RESONANCE; ASCORBIC-ACID; XANTHINE-OXIDASE; GLUTATHIONE; PEROXIDASE; OXIDATION; ACETAMINOPHEN; METABOLISM; GENERATION; SCHIZOPHRENIA AB The use of clozapine, a unique antipsychotic drug, has been restricted due to a 1-2% incidence of drug-induced agranulocytosis. Metabolic activation of clozapine in neutrophils or stem cells could be the molecular mechanism underlying this side effect. Clozapine oxidation by human myeloperoxidase and horseradish peroxidase was evident from the disappearance of the UV absorbance at 290 nm. High performance liquid chromatography analysis revealed the formation of at least four radioactive peaks as a result of clozapine metabolism, including radioactivity coeluting with the protein. The tight association of radioactivity with the enzymatic protein was metabolism-dependent. This protein binding, which correlates with the total metabolism of clozapine, was reduced in the presence of glutathione and was absent in the presence of ascorbate. Similarly, in the presence of both reducing agents, the metabolite peaks in the high performance liquid chromatography radiogram, which are not associated with protein, disappeared. In contrast, in the presence of glutathione, two additional metabolites were found that could be isolated and identified by NMR and mass spectroscopy as clozapine glutathionyl adducts. Evidence for one-electron transfer reactions or the intermediate formation of a clozapine radical during the peroxidase-mediated metabolism of clozapine stems from the observation of thiyl and ascorbyl radicals in the presence of glutathione and ascorbate, respectively. The ascorbyl radical was detected by direct ESR spectroscopy in a peroxidase system. Its steady state concentration was significantly increased in the presence of clozapine. Glutathionyl radical formation was demonstrated by radical trapping with 5,5-dimethyl-1-pyrroline N-oxide in a peroxidase system. Again, the radical adduct concentration was significantly increased in the presence of clozapine. Similarly, when oxygen consumption was measured in peroxidase systems in the presence of glutathione or NADPH, the rate of oxygen uptake was markedly enhanced upon addition of clozapine. Thus, the data support the possibility of clozapine activation to free radical metabolites, which may cause oxidative stress or lead to adduct formation. Further, it can be concluded from these data that radical scavengers such as ascorbic acid, when coadministered with clozapine to patients, may reduce oxidative stress and protein adduct formation. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. RP FISCHER, V (reprint author), SANDOZ PHARM LTD,DEPT DRUG SAFETY,BLDG 507-704,CH-4002 BASEL,SWITZERLAND. NR 35 TC 98 Z9 99 U1 0 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 1991 VL 40 IS 5 BP 846 EP 853 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GQ445 UT WOS:A1991GQ44500034 PM 1658615 ER PT J AU MAGIN, GK ROBISON, SH BRESLIN, N WYATT, RJ ALEXANDER, RC AF MAGIN, GK ROBISON, SH BRESLIN, N WYATT, RJ ALEXANDER, RC TI DNA-REPAIR AND MUTANT FREQUENCY IN SCHIZOPHRENIA SO MUTATION RESEARCH LA English DT Article DE DNA REPAIR; HPRT MUTANT FREQUENCY; SCHIZOPHRENIA ID HUMAN LYMPHOCYTES-T; CLONING; DISEASE; INVIVO; ASSAY AB The in vivo frequency of mutants resulting from mutation at the hprt locus in human T-lymphocytes was determined with a cloning assay. T-lymphocytes were obtained from 14 individuals diagnosed with schizophrenia and 5 controls. No significant difference in mutant frequency was observed between the 2 groups. In addition, DNA-repair capacity was measured with the unscheduled DNA synthesis technique in lymphocytes from 7 individuals diagnosed with schizophrenia and 7 controls. Repair capacity was determined following treatment with MMS, MNNG, and 20 J/m2 ultraviolet light. No significant differences in DNA repair were observed between the patient and control groups in response to any of the 3 DNA-damaging agents. These results argue against differences between normal and schizophrenic individuals with respect to in vivo mutant frequency or their capacity to repair DNA lesions induced by MMS, MNNG, or ultraviolet radiation. C1 UNIV VERMONT,VERMONT REG CANC CTR,GENET LAB,BURLINGTON,VT 05401. ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. NR 18 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD NOV PY 1991 VL 255 IS 3 BP 241 EP 246 DI 10.1016/0921-8777(91)90027-M PG 6 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA GP085 UT WOS:A1991GP08500004 PM 1719395 ER PT J AU BARRETT, SF ROBBINS, JH TARONE, RE KRAEMER, KH AF BARRETT, SF ROBBINS, JH TARONE, RE KRAEMER, KH TI EVIDENCE FOR DEFECTIVE REPAIR OF CYCLOBUTANE PYRIMIDINE DIMERS WITH NORMAL REPAIR OF OTHER DNA PHOTOPRODUCTS IN A TRANSCRIPTIONALLY ACTIVE GENE TRANSFECTED INTO COCKAYNE SYNDROME CELLS SO MUTATION RESEARCH LA English DT Article DE DNA REPAIR; XERODERMA-PIGMENTOSUM; UV RADIATION; PLASMID EXPRESSION ID XERODERMA PIGMENTOSUM-CELLS; SISTER CHROMATID EXCHANGES; IRRADIATED MAMMALIAN-CELLS; ULTRAVIOLET-LIGHT; COMPLEMENTATION GROUPS; UV; FIBROBLASTS; DAMAGE; CANCER; LINES AB Cockayne syndrome (CS) and xeroderma pigmentosum (XP), autosomal recessive diseases with clinical and cellular hypersensitivity to UV radiation, differ in ability to repair UV DNA photoproducts in their overall genome: normal repair in CS, defective repair in XP. In order to characterize a DNA in their overall genome: normal repair in CS, defective repair in XP. In order to characterize a DNA repair defect in an active gene in CS, we measured the capacity of cells from patients with CS and XP to reactivate 2 major types of UV-induced DNA damage, photoreactivatable (i.e., cyclobutane pyrimidine dimers) and non-photoreactivatable (primarily pyrimidine-(6-4)pyrimidone photoproducts), in the actively transcribing chloramphenicol acetyltransferase (cat) gene of the plasmid expression vector pRSV-cat. Epstein-Barr virus-transformed lymphoblast lines from 4 normal persons and from 3 patients with CS and from two with XP were transiently transfected with the plasmid, and the cat activity in cell extracts was determined. When the cells were transfected with UV-irradiated plasmid, cat expression was abnormally decreased in both the CS and XP cells. When the cyclobutane pyrimidine dimers in the UV-irradiated plasmid were removed by photoreactivation prior to transfection, cat expression in the CS, but not in the XP, lines reached normal levels. These data imply that both the XP and CS cells are unable to repair normally the cyclobutane pyrimidine dimer photoproducts which blocks transcription of cat. However, the CS, but not XP, cells can repair normally the other UV-induced photoproducts which block transcription. The ability of CS, but not XP, cells to repair these non-dimer photoproducts indicates that the active gene repair mechanism treats the cyclobutane pyrimidine dimer differently from the non-dimer photoproducts. C1 NCI,MOLEC CARCINOGENESIS LAB,BLDG 37,ROOM 3E24,BETHESDA,MD 20892. NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. FU Intramural NIH HHS [Z01 BC004517-31] NR 39 TC 38 Z9 38 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 NOV PY 1991 VL 255 IS 3 BP 281 EP 291 DI 10.1016/0921-8777(91)90032-K PG 11 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA GP085 UT WOS:A1991GP08500009 PM 1719400 ER PT J AU SZALLASI, A SZOLCSANYI, J SZALLASI, Z BLUMBERG, PM AF SZALLASI, A SZOLCSANYI, J SZALLASI, Z BLUMBERG, PM TI INHIBITION OF [H-3] RESINIFERATOXIN BINDING TO RAT DORSAL-ROOT GANGLION MEMBRANES AS A NOVEL-APPROACH IN EVALUATING COMPOUNDS WITH CAPSAICIN-LIKE ACTIVITY SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Article DE [H-3]RESINIFERATOXIN BINDING; RESINIFERATOXIN ANALOGS; CAPSAICIN ANALOGS ID PRIMARY SENSORY NEURONS; CHEMICAL-STRUCTURE; RESINIFERATOXIN; ANALOGS; PHARMACOLOGY; CONGENERS; ESTERS AB We have recently reported the specific binding of [H-3]resiniferatoxin to sensory ganglion membranes; this binding appears to represent the postulated vanilloid (capsaicin) receptor. In the present report, we compare the structure/activity relations for binding to rat dorsal root ganglion membranes and for biological responses in the rat, using a series of vanilloids of the capsaicin (homovanilloyl-decylamide, homovanilloyl-dodecylamide, homovanilloyl-cyclododecylamide, homovanilloyl-hexadecylamide, homovanilloyl-piperidine and nonenoyl-homoveratrylamide) and resiniferatoxin (tinyatoxin, 12-deoxyphorbol 13-phenylacetate 20-homovanillate) classes. We find that all the tested biologically active vanilloids, but not the inactive structure analogs, compete for the [H-3]resiniferatoxin binding sites in rat dorsal root ganglion membranes, and we conclude that the [H-3]resiniferatoxin binding assay may provide an efficient approach for evaluating such compounds. We also provide evidence that the [H-3]resiniferatoxin receptor is likely to recognize vanilloids which are inserted into the membranes; and that the apparent activity of capsaicinoids may be significantly influenced by factors other than equilibrium binding affinities. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. UNIV PECS,SCH MED,DEPT PHARMACOL,H-7643 PECS,HUNGARY. NR 32 TC 24 Z9 24 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD NOV PY 1991 VL 344 IS 5 BP 551 EP 556 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GP741 UT WOS:A1991GP74100008 PM 1811172 ER PT J AU SPROTT, RL AF SPROTT, RL TI DEVELOPMENT OF ANIMAL-MODELS OF AGING AT THE NATIONAL-INSTITUTE-ON-AGING SO NEUROBIOLOGY OF AGING LA English DT Article; Proceedings Paper CT CONF ON ANIMAL MODELS FOR AGING RESEARCH CY SEP 26-28, 1990 CL VENICE, ITALY SP ASSOC INT RECH ENSEIGNEMENT NEUROSCI, FRIULI ANIM RES INST VET RES & DEV DE NATIONAL-INSTITUTE-ON-AGING; AGING, ANIMAL MODELS; AGING, GENETICS; AGED RODENTS, PATHOLOGY; AGED RATS; AGED MICE AB The suitability of various animal species as experimental models of aging has been a continuing concern of the National Institute on Aging (NIA) for over 20 years. The history of the decisions made by NIA in providing aged animals for research may be helpful to individual investigators seeking to understand why certain models are available and which of them to choose for their work. RP SPROTT, RL (reprint author), NIA,BIOL AGING PROGRAM,7201 WISCONSIN AVE,ROOM 2C231,BETHESDA,MD 20892, USA. NR 0 TC 43 Z9 43 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD NOV-DEC PY 1991 VL 12 IS 6 BP 635 EP 638 DI 10.1016/0197-4580(91)90113-X PG 4 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA GQ465 UT WOS:A1991GQ46500003 PM 1791897 ER PT J AU HAZZARD, DG AF HAZZARD, DG TI RELEVANCE OF THE RODENT MODEL TO HUMAN AGING STUDIES SO NEUROBIOLOGY OF AGING LA English DT Article; Proceedings Paper CT CONF ON ANIMAL MODELS FOR AGING RESEARCH CY SEP 26-28, 1990 CL VENICE, ITALY SP ASSOC INT RECH ENSEIGNEMENT NEUROSCI, FRIULI ANIM RES INST VET RES & DEV DE AGING, ANIMAL MODELS; AGING, ANATOMY; AGING, PHYSIOLOGY; AGING, LEARNING AND MEMORY; AGED RATS; AGED MICE ID SENESCENCE; CELLS; BRAIN AB Rodents have proven to be a useful general model for aging research. Although they are not necessarily appropriate for the study of such specific human age-associated diseases as atherosclerosis, rodents have provided the basis for important age-related findings in many diverse areas, including nutrition, behavior, immunology, physiology, oncology, biochemistry, and neurobiology. Contributions in these areas are briefly reviewed. RP HAZZARD, DG (reprint author), NIA,BIOL AGING PROGRAM,OFF RESOURCE DEV,7201 WISCONSIN AVE,SUITE 2C231,BETHESDA,MD 20892, USA. NR 29 TC 21 Z9 21 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD NOV-DEC PY 1991 VL 12 IS 6 BP 645 EP 649 DI 10.1016/0197-4580(91)90115-Z PG 5 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA GQ465 UT WOS:A1991GQ46500005 PM 1791899 ER PT J AU DALY, JW NISHIZAWA, Y PADGETT, WL TOKUYAMA, T MCCLOSKEY, PJ WAYKOLE, L SCHULTZ, AG ARONSTAM, RS AF DALY, JW NISHIZAWA, Y PADGETT, WL TOKUYAMA, T MCCLOSKEY, PJ WAYKOLE, L SCHULTZ, AG ARONSTAM, RS TI DECAHYDROQUINOLINE ALKALOIDS - NONCOMPETITIVE BLOCKERS FOR NICOTINIC ACETYLCHOLINE RECEPTOR-CHANNELS IN PHEOCHROMOCYTOMA CELLS AND TORPEDO ELECTROPLAX SO NEUROCHEMICAL RESEARCH LA English DT Article DE ACETYLCHOLINE RECEPTORS; NICOTINIC NONCOMPETITIVE BLOCKERS; DESENSITIZATION ID ION CONDUCTANCE MODULATOR; PUMILIOTOXIN-C; POISON FROGS; HISTRIONICOTOXIN; INHIBITION; PERHYDROHISTRIONICOTOXIN; DERIVATIVES; ANTAGONISTS; BINDING; MUSCLE AB In pheochromocytoma PC12 cells, (+)-cis-decahydroquinoline 195A (5-methyl-2-propyl-cis-decahydroquinoline) and (+)-perhydro-cis-decahydroquinoline 219A (2,5-dipropyl-cis-decahydroquinoline) inhibit carbamylcholine-elicited sodium flux with IC50 values of 1.0 and 1.5-mu-M, respectively. Both of these decahydroquinolines appear to enhance desensitization, although apparent lack of complete removal of (+)-perhydro-cis-219A by washing complicates interpretation of the effects of that agent. A series of cis- and trans-decahydroquinolines with substituents in the 2- and 5-position also exhibit structure-dependent inhibition of carbamylcholine-elicited sodium flux in PC12 cells and all of the decahydroquinolines inhibit binding of the noncompetitive blocking agent [H-3]perhydrohistrionicotoxin to muscle-type nicotinic acetylcholine receptor-channels in membranes from Torpedo electroplax. The K(i) values in electroplax membranes range from 1.4 to 7.9-mu-M, making these alkaloids comparable in potencies to the histrionicotoxins. Potencies are increased 2- to 3-fold in the presence of an agonist, carbamylcholine. The profile of activities are similar in PC12 cells and electroplax membranes. The cis- and trans-decahydroquinolines represent another class of noncompetitive blockers for acetylcholine receptor-channels with similar activity for both muscle-type and ganglionic type nicotinic receptors. C1 OSAKA CITY UNIV,FAC SCI,OSAKA 558,JAPAN. RENSSELAER POLYTECH INST,DEPT CHEM,TROY,NY 12180. MED COLL GEORGIA,DEPT PHARMACOL & TOXICOL,AUGUSTA,GA 30912. RP DALY, JW (reprint author), NIH,BIOORGAN CHEM LAB,BETHESDA,MD 20892, USA. NR 30 TC 33 Z9 33 U1 0 U2 4 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD NOV PY 1991 VL 16 IS 11 BP 1207 EP 1212 DI 10.1007/BF00966697 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA GL501 UT WOS:A1991GL50100004 PM 1815136 ER PT J AU DALY, JW NISHIZAWA, Y PADGETT, WL TOKUYAMA, T SMITH, AL HOLMES, AB KIBAYASHI, C ARONSTAM, RS AF DALY, JW NISHIZAWA, Y PADGETT, WL TOKUYAMA, T SMITH, AL HOLMES, AB KIBAYASHI, C ARONSTAM, RS TI 5,8-DISUBSTITUTED INDOLIZIDINES - A NEW CLASS OF NONCOMPETITIVE BLOCKERS FOR NICOTINIC RECEPTOR-CHANNELS SO NEUROCHEMICAL RESEARCH LA English DT Article DE ACETYLCHOLINE RECEPTORS; INDOLIZIDINES; NONCOMPETITIVE BLOCKERS ID ACETYLCHOLINE-RECEPTOR; TORPEDO ELECTROPLAX; IONIC CHANNEL; POISON-FROG; ALKALOIDS; COMPLEX; PERHYDROHISTRIONICOTOXIN; DESENSITIZATION; DENDROBATIDAE; GEPHYROTOXIN AB A series of 8-methyl-5-substituted indolizidines inhibit binding of the noncompetitive blocking agent [H-3]perhydrohistrionicotoxin to muscle-type nicotinic acetylcholine receptor-channels in membranes from Torpedo electroplax. The K(i) values range from 0.16 to 1.12-mu-M, making these alkaloids among the most potent ligands for this site. Unlike most noncompetitive blockers, the potencies of the 8-methyl-5-substituted indolizidines are reduced in the presence of carbamylcholine. Indolizidine 205A (8-methyl-5-(4-pentynyl)indolizidine) is unique in enhancing binding of [H-3]perhydrohistrionicotoxin by 1.5-fold. The enhancement is at a maximum at 0.01 to 0.1-mu-M, followed by progressive inhibition with an IC50 of about 20-mu-M. In the presence of carbamylcholine, which itself enhances binding of [H-3]perhydrohistrionicotoxin, indolizidine 205A causes only an inhibition of binding with an IC50 of about 10-mu-M. Indolizidines with a hydroxy substituent on the 8-methyl group have very low activity. None of the indolizidines affect binding of [I-125]alpha-bungarotoxin to acetylcholine recognition sites. In pheochromocytoma PC12 cells, indolizidine 205A has no agonist activity, but only inhibits carbamylcholine-elicited Na-22+ influx. The profile of potencies for the 8-methyl-5-substituted indolizidines is similar in electroplax membranes and PC12 cells. Indolizidines 205A and 209B (8-methyl-5-pentylindolizidine) have no apparent effect on desensitization of receptors in PC12 cells. The 5,8-disubstituted indolizidines appear to represent an atypical and potent class of noncompetitive blockers for muscle-type and ganglionic nicotinic receptor-channels. C1 OSAKA CITY UNIV,FAC SCI,OSAKA 558,JAPAN. UNIV CAMBRIDGE,CHEM LAB,CAMBRIDGE CB2 1EW,ENGLAND. TOKYO COLL PHARM,HACHIOJI,TOKYO 19203,JAPAN. MED COLL GEORGIA,DEPT PHARMACOL & TOXICOL,AUGUSTA,GA 30912. RP DALY, JW (reprint author), NIH,BIOORGAN CHEM LAB,BETHESDA,MD 20892, USA. NR 22 TC 31 Z9 31 U1 0 U2 5 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD NOV PY 1991 VL 16 IS 11 BP 1213 EP 1218 DI 10.1007/BF00966698 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA GL501 UT WOS:A1991GL50100005 PM 1815137 ER PT J AU MICHELS, KM SAAVEDRA, JM AF MICHELS, KM SAAVEDRA, JM TI DIFFERENTIAL DEVELOPMENT OF INSULIN-LIKE GROWTH FACTOR-I BINDING IN THE SUPRACHIASMATIC NUCLEUS AND MEDIAN-EMINENCE OF THE RAT HYPOTHALAMUS SO NEUROENDOCRINOLOGY LA English DT Article DE INSULIN-LIKE GROWTH FACTORS; SUPRACHIASMATIC NUCLEUS; MEDIAN EMINENCE; DEVELOPMENT; INSULIN-LIKE GROWTH FACTOR-I RECEPTORS; HYPOTHALAMUS; FETUS ID CENTRAL NERVOUS-SYSTEM; QUANTITATIVE AUTORADIOGRAPHY; THYROID-HORMONE; GENE-EXPRESSION; PITUITARY-GLAND; CHOROID-PLEXUS; BRAIN; RECEPTORS; LOCALIZATION; SITES AB We investigated the in vitro binding of [I-125]insulin-like growth factor I ([I-125]IGF-I) within the suprachiasmatic nucleus (SCN) and median eminence (ME) of the rat by quantative autoradiography. Binding of [I-125]IGF-I within the adult SCN was saturable, reversible and to a single class of sites with an estimated K(d) of 3.01 x 10(-10) M and B(max) of 131 fmol/mg protein. Competition studies revealed [I-125]IGF-I binding within the SCN and ME to have the pharmacological specificity characteristic of the brain IGF-I receptor. The most potent competitors were IGF-I and IGF-II, while insulin displaced binding with a much lower potency and nerve growth factor 7S had no effect. Binding within the SCN was evident by embryonic day 18, peaked perinatally, declined to adult levels by day 6 and remained constant through middle age. The potency of IGF-I to displace [I-125]IGF-I binding from SCN was similar among all ages. Binding in the ME was not evident until postnatal day 2, peaked near the end of the 1st week, declined to adult levels by day 9 and remained constant thereafter. There was no difference in binding in SCN or ME between day and early night, in animals with acute or long-term eye enucleation, or in animals fed a high sucrose diet. These results demonstrate differential development of [I-125]IGF-I binding within the SCN and ME and support a role for IGFs in both these nuclei during development and maturity. RP MICHELS, KM (reprint author), NIMH,CLIN SCI LAB,PHARMACOL SECT,BLDG 10,ROOM 2D-45,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 47 TC 9 Z9 10 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD NOV PY 1991 VL 54 IS 5 BP 504 EP 514 DI 10.1159/000125945 PG 11 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA GM455 UT WOS:A1991GM45500013 PM 1660966 ER PT J AU KOW, LM JOHNSON, AE OGAWA, S PFAFF, DW AF KOW, LM JOHNSON, AE OGAWA, S PFAFF, DW TI ELECTROPHYSIOLOGICAL ACTIONS OF OXYTOCIN ON HYPOTHALAMIC NEURONS INVITRO - NEUROPHARMACOLOGICAL CHARACTERIZATION AND EFFECTS OF OVARIAN-STEROIDS SO NEUROENDOCRINOLOGY LA English DT Article DE ACETYLCHOLINE; BRAIN SLICES; ESTROGEN; HYPOTHALAMIC VENTROMEDIAL NUCLEUS; LORDOSIS; NEURONAL ACTIVITY; NOREPINEPHRINE; OXYTOCIN; PROGESTERONE; VASOPRESSIN ID FEMALE RATS; VENTROMEDIAL NUCLEUS; CENTRAL GRAY; SEXUAL RECEPTIVITY; ESTROGEN-TREATMENT; LORDOSIS BEHAVIOR; RECEPTOR-BINDING; PREOPTIC AREA; MESSENGER-RNA; PROGESTERONE AB Oxytocin (OT) neurotransmission in the brain has a facilitatory effect on sexual receptivity in rats. This effect of OT is dependent on priming by ovarian steroids, estrogen and progesterone. These steroids modulate OT binding in specific brain nuclei, including the ventrolateral portion of the ventromedial hypothalamic nucleus (vlVMN). In the present study, single-unit activity was recorded from the vlVMN in hypothalamic slices to characterize the electrophysiological actions of OT. To examine the effects of ovarian steroids on OT actions, we used brain slices prepared from ovariectomized rats either treated with estrogen or not, and some slices were treated with progesterone in vitro. OT had little modulatory action on neuronal responses to other agents, but affected the activity of large numbers of vlVMN units. Of those neurons affected, 94% responded with excitation. This predominant stimulatory action of OT is consistent with its lordosis-facilitating effect, because increases in the activity of VMN neurons are generally associated with the facilitation of lordosis. Pharmacological analyses with selective OT agonists and antagonists as well as structurally related peptides showed that the excitatory action of OT is mediated by OT receptors. Estradiol modulated several aspects of OT transmission. First, it increased neuronal responsiveness to OT, especially at the lowest concentration used (0.2 nM). In addition, it caused neuronal responses to OT to correlate significantly with responses to acetylcholine and norepinephrine, which also can act on the ventromedial hypothalamus to facilitate lordosis. Finally, estradiol enhanced the excitability of laterally projecting neurons, which have been implicated in lordosis. In estrogen-pretreated slices, addition of progesterone in vitro caused little further effect on responses of individual neurons to exogenous OT. Altogether, the present electrophysiological findings are consistent with the hypothesis that estrogen potentiates OT action by increasing functional OT receptors preferentially in lordosis-relevant neurons, thereby enabling OT to efficiently facilitate female reproductive behavior. C1 NIMH,CLIN SCI LAB,SCSBB,POOLESVILLE,MD. RP KOW, LM (reprint author), ROCKEFELLER UNIV,NEUROBIOL & BEHAV LAB,1230 YORK AVE,NEW YORK,NY 10021, USA. FU NICHD NIH HHS [HD-05751] NR 49 TC 60 Z9 60 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD NOV PY 1991 VL 54 IS 5 BP 526 EP 535 DI 10.1159/000125948 PG 10 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA GM455 UT WOS:A1991GM45500016 PM 1749464 ER PT J AU GOETZ, CG STEBBINS, GT KLAWANS, HL KOLLER, WC GROSSMAN, RG BAKAY, RAE PENN, RD AF GOETZ, CG STEBBINS, GT KLAWANS, HL KOLLER, WC GROSSMAN, RG BAKAY, RAE PENN, RD TI UNITED-PARKINSON-FOUNDATION NEUROTRANSPLANTATION REGISTRY ON ADRENAL-MEDULLARY TRANSPLANTS - PRESURGICAL, AND 1-YEAR AND 2-YEAR FOLLOW-UP SO NEUROLOGY LA English DT Article ID DISEASE; MULTICENTER; NERVE AB Thirteen centers participated in a multicenter database with systematic evaluation of US and Canadian patients who had adrenal medullary transplantation for Parkinson's disease. This voluntary registry collected demographic, safety, and efficacy data using the same scoring measures over a 2-year follow-up period. Baseline data on 61 patients and 2-year follow-up data on 56 patients were compared. Eighteen percent died during the study period, and one-half of these deaths were related or questionably related to the surgery. Of the remaining 45 patients with data, global improvement, defined as an improved summed score of the "on" and "off" motor and activities of daily living functions from the Unified Parkinson's Disease Rating Scale, occurred in 32% of the patients at 2 years after surgery. At follow-up, significant group improvement persisted in the amount of daily "on" time and the quality of "off" function, but other measures were no better than baseline. When the global improvement calculation was based on the total sample and included deaths and patients lost to follow-up as "not improved," only 19% were improved 2 years after surgery. Twenty-two percent of survivors had persistent psychiatric morbidity not present prior to surgery. These data document a modest group improvement in "off" function after neurotransplantation, but a serious level of mortality and morbidity. C1 RUSH UNIV, UNITED PARKINSON FDN, NEUROTRANSPLANTAT REGISTRY GRP, CHICAGO, IL 60612 USA. NYU, NEW YORK, NY 10003 USA. UNIV OTTAWA, OTTAWA K1N 6N5, ONTARIO, CANADA. BAYLOR UNIV, WACO, TX 76798 USA. NIH, BETHESDA, MD 20892 USA. UNIV PITTSBURGH, PITTSBURGH, PA 15260 USA. UNIV KANSAS, LAWRENCE, KS 66045 USA. UNIV SO CALIF, LOS ANGELES, CA 90089 USA. EMORY UNIV, ATLANTA, GA 30322 USA. COLUMBIA UNIV, NEW YORK, NY 10027 USA. UNIV CALIF LOS ANGELES, LOS ANGELES, CA 90024 USA. UNIV CALIF SAN DIEGO, LA JOLLA, CA 92093 USA. NR 13 TC 99 Z9 101 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD NOV PY 1991 VL 41 IS 11 BP 1719 EP 1722 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA GQ467 UT WOS:A1991GQ46700002 PM 1944898 ER PT J AU WENK, GL NAIDU, S CASANOVA, MF KITT, CA MOSER, H AF WENK, GL NAIDU, S CASANOVA, MF KITT, CA MOSER, H TI ALTERED NEUROCHEMICAL MARKERS IN RETTS SYNDROME SO NEUROLOGY LA English DT Article ID BASAL FOREBRAIN NEURONS; BIOGENIC-AMINES; POSTMORTEM BRAIN; DISEASE; METABOLITES; MEMBRANES; DEMENTIA; BINDING; AUTISM; SITES AB Rett's syndrome (RS) is a neurologic disorder associated with severe mental deficiency and neurologic manifestations of cortical and extrapyramidal origin. The present report is a preliminary postmortem brain study that compares the levels of endogenous biogenic amines and selected neurotransmitter receptors in five cases with RS and six normal controls of similar age. The level of choline acetyltransferase activity was reduced in several cortical and subcortical regions. Endogenous levels of dopamine in the superior frontal and superior temporal gyri, occipital cortex, and putamen were reduced. The changes in specific neurotransmitter markers, particularly those associated with the basal ganglia and cortex, may underlie the progressive deterioration in motor and cognitive function characteristic of this progressive disorder. C1 JOHNS HOPKINS UNIV,NEUROMNEMON LAB,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,DEPT PSYCHOL,BALTIMORE,MD 21218. KENNEDY INST HANDICAPPED CHILDREN,BALTIMORE,MD. NIMH,INTRAMURAL RES PROGRAM,WASHINGTON,DC 20032. JOHNS HOPKINS UNIV HOSP,DEPT NEUROL & PEDIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,NEUROPATHOL LAB,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205. NIMH,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. RP WENK, GL (reprint author), UNIV ARIZONA,ARIZONA HLTH SCI CTR,DIV NEURAL SYST MEMORY & AGING,384 LIFE SCI N BLDG,TUCSON,AZ 85724, USA. FU NICHD NIH HHS [P01-HD-23540] NR 23 TC 60 Z9 60 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 1991 VL 41 IS 11 BP 1753 EP 1756 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA GQ467 UT WOS:A1991GQ46700010 PM 1658685 ER PT J AU WASSERMANN, EM FUHR, P COHEN, LG HALLETT, M AF WASSERMANN, EM FUHR, P COHEN, LG HALLETT, M TI EFFECTS OF TRANSCRANIAL MAGNETIC STIMULATION ON IPSILATERAL MUSCLES SO NEUROLOGY LA English DT Article ID MOTOR CORTEX STIMULATION; CORTICOSPINAL TRACT; INTACT MAN; MONKEY; ARM; MOVEMENTS; RESPONSES; MYOCLONUS; NEURON; HAND AB We studied the effects of transcranial magnetic stimulation of the motor cortex on ipsilateral upper extremity muscles in six normal men. Stimulation had inhibitory and excitatory effects on the muscles during voluntary activation. Transient inhibition, an ipsilateral silent period (ISP), occurred in all muscles tested, often without any preceding excitatory response. Motor evoked potentials (MEPs) occurred ipsilaterally in the proximal muscles of some subjects. Ipsilateral MEPs and ISPs were delayed relative to the MEPs evoked by the same stimulus in the corresponding contralateral muscles. The excitability of the alpha motoneuron pool, assessed during the period of the ISP by eliciting H-reflexes, showed no change, suggesting that ipsilateral inhibition acts at a level above the alpha motoneuron. Connections from motor cortex to ipsilateral muscles could be via the corpus callosum and contralateral hemisphere or via purely ipsilateral pathways. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,HUMAN CORT PHYSIOL UNIT,BETHESDA,MD 20892. RP WASSERMANN, EM (reprint author), NINCDS,OFF CLIN DIRECTOR,BLDG 10,ROOM 5N226,BETHESDA,MD 20892, USA. NR 40 TC 197 Z9 199 U1 1 U2 5 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 1991 VL 41 IS 11 BP 1795 EP 1799 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA GQ467 UT WOS:A1991GQ46700017 PM 1944911 ER PT J AU BOLLA, KI MILSTIEN, S BRIEFEL, G WIELER, L KAUFMAN, S AF BOLLA, KI MILSTIEN, S BRIEFEL, G WIELER, L KAUFMAN, S TI DIHYDROPTERIDINE REDUCTASE-ACTIVITY - LACK OF ASSOCIATION WITH SERUM ALUMINUM LEVELS AND COGNITIVE-FUNCTIONING IN PATIENTS WITH END-STAGE RENAL-DISEASE SO NEUROLOGY LA English DT Article ID DIALYSIS ENCEPHALOPATHY; INHIBITION; DEFICIENCY; DEMENTIA; HEMODIALYSIS; ENZYME; ASSAY; GELS AB Although increased levels of aluminum (Al) are present in patients with dialysis encephalopathy (DE), it is unclear if the association is causal. The enzyme dihydropteridine reductase (DHPR) plays a critical role in neurotransmitter formation and its activity. Elevated levels of Al are reported to decrease DHPR activity, which would alter neurotransmitter metabolism, thus producing DE. We examined the association between erythrocyte DHPR activity and Al levels, attention/pyschomotor skills, and depression in a group of 21 patients with end-stage renal disease. DHPR activity was not related to Al level, mental status, psychomotor ability, or depression score. After administration of deferoxamine (an Al chelating agent), Al level increased significantly but DHPR activity remained the same. Our results suggest that the mechanism for the development for DE does not involve alterations of neurotransmitter metabolism caused by Al-mediated reductions in DHPR activity. C1 JOHNS HOPKINS UNIV,FRANCIS SCOTT KEY MED CTR,SCH MED,DEPT NEPHROL,BALTIMORE,MD 21224. NIMH,NEUROCHEM LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21224. RP BOLLA, KI (reprint author), JOHNS HOPKINS UNIV,FRANCIS SCOTT KEY MED CTR,SCH MED,DEPT NEUROL,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. FU NIEHS NIH HHS [1R29ES04427] NR 28 TC 5 Z9 5 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 1991 VL 41 IS 11 BP 1806 EP 1809 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA GQ467 UT WOS:A1991GQ46700019 PM 1944913 ER PT J AU BERKEMEIER, LR WINSLOW, JW KAPLAN, DR NIKOLICS, K GOEDDEL, DV ROSENTHAL, A AF BERKEMEIER, LR WINSLOW, JW KAPLAN, DR NIKOLICS, K GOEDDEL, DV ROSENTHAL, A TI NEUROTROPHIN-5 - A NOVEL NEUROTROPHIC FACTOR THAT ACTIVATES TRK AND TRKB SO NEURON LA English DT Article ID NERVE GROWTH-FACTOR; DORSAL-ROOT GANGLIA; MESSENGER-RNA; MOLECULAR-CLONING; FACTOR FAMILY; SYMPATHETIC INNERVATION; CHOLINERGIC NEURONS; SENSORY NEURONS; FACTOR NGF; EXPRESSION AB In vertebrates, the formation and maintenance of neuronal connections are subject to regulation by multiple target-derived, diffusible (neurotrophic) factors. Here we describe the identification and characterization of a novel neurotrophic factor designated neurotrophin-5 (NT-5). NT-5 is structurally related to nerve growth factor and is expressed in embryonic as well as adult tissues. Recombinant NT-5 promotes the survival of peripheral sensory and sympathetic neurons and induces differentiation of the pheochromocytoma cell line PC12. NT-5 activates two trk-related tyrosine kinase receptors and shares these receptors with other neurotrophins. Activation of multiple receptors may permit a single neurotrophin to control target innervation by distinct neuronal populations. Receptor sharing could enable neurotrophic factors emanating from distinct targets to cooperate in regulating neurons with multiple connections. C1 GENENTECH INC,DEPT DEV BIOL,S SAN FRANCISCO,CA 94080. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MMCL,FREDERICK,MD 21701. RP BERKEMEIER, LR (reprint author), GENENTECH INC,DEPT MOLEC BIOL,S SAN FRANCISCO,CA 94080, USA. FU NCI NIH HHS [N01-CO-74101] NR 59 TC 728 Z9 739 U1 1 U2 13 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD NOV PY 1991 VL 7 IS 5 BP 857 EP 866 DI 10.1016/0896-6273(91)90287-A PG 10 WC Neurosciences SC Neurosciences & Neurology GA GT939 UT WOS:A1991GT93900015 PM 1742028 ER PT J AU HOFFMAN, PL DAVE, JR AF HOFFMAN, PL DAVE, JR TI CHRONIC ETHANOL EXPOSURE UNCOUPLES VASOPRESSIN SYNTHESIS AND SECRETION IN RATS SO NEUROPHARMACOLOGY LA English DT Note DE HYPOTHALAMIC VASOPRESSIN MESSENGER RNA; CHRONIC ETHANOL EXPOSURE; VASOPRESSIN SYNTHESIS-SECRETION COUPLING ID MESSENGER-RNA; GENE-EXPRESSION; STIMULATION AB To assess the chronic effect of ethanol on vasopress in release and synthesis, hypothalamic vasopressin mRNA, plasma vasopressin levels and plasma osmolality were measured in control rats and rats exposed chronically to ethanol by vapor inhalation for 8 days. The level of hypothalamic vasopressin mRNA (vasopressin synthesis) was unchanged or significantly decreased in ethanol-treated rats, even when these animals displayed increased plasma osmolality and vasopressin levels. The results suggest that chronic ethanol exposure produces a down-regulation of vasopressin synthesis and/or a disruption of vasopressin synthesis-secretion coupling. These findings may have important implications for evaluation of the hydration state of chronic alcoholics. C1 NATL INST ALCOHOL ABUSE & ALCOHOLISM,DIV INTRAMURAL CLIN & BIOL RES,ROCKVILLE,MD 20852. NR 10 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD NOV PY 1991 VL 30 IS 11 BP 1245 EP 1249 DI 10.1016/0028-3908(91)90172-8 PG 5 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA GN931 UT WOS:A1991GN93100015 PM 1775224 ER PT J AU CROFTON, KM HOWARD, JL MOSER, VC GILL, MW REITER, LW TILSON, HA MACPHAIL, RC AF CROFTON, KM HOWARD, JL MOSER, VC GILL, MW REITER, LW TILSON, HA MACPHAIL, RC TI INTERLABORATORY COMPARISON OF MOTOR-ACTIVITY EXPERIMENTS - IMPLICATIONS FOR NEUROTOXICOLOGICAL ASSESSMENTS SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE MOTOR ACTIVITY; INTERLABORATORY COMPARISON; NEUROTOXICOLOGY; WITHIN-LABORATORY VARIABILITY; WITHIN-LABORATORY RELIABILITY ID BASAL LOCOMOTOR-ACTIVITY; ACOUSTIC STARTLE RESPONSE; LABORATORY RODENTS; TRIAZOLE FUNGICIDE; BEHAVIORAL-TESTS; WISTAR RATS; MICE; NEUROTOXICITY; SCOPOLAMINE; VARIABILITY AB Motor activity is an important functional measure used in neurotoxicology. The effects of chemicals on motor activity, however, may depend on variables such as type of measurement apparatus, physical and environmental testing conditions, and many other experimental protocol and organismic variables. Due to the increasing use of motor activity in neurotoxicology, a major question concerns the potential for differences in experimental findings due to variations in sensitivity and reliability between different laboratories and devices used to measure motor activity. This study examined historical data from a number of laboratories that employed different devices and experimental protocols to measure motor activity. Four aspects of the motor activity data were compared: 1) within-laboratory control variability across time; 2) within-laboratory replicability of control data; 3) between-laboratory variability in the effects of chemicals; and 4) between-laboratory comparison of the control rates of habituation. The analyses indicated that there was a relatively restricted range of within-laboratory variability and reliability in control values, and that these ranges were comparable across laboratories. Similar profiles of habituation were also seen across the different laboratories. Moreover, in virtually every case, all laboratories were capable of detecting qualitatively similar changes in motor activity following acute exposure to a variety of chemicals. These data indicate a high degree of comparability in the data generated by the different devices and experimental protocols. C1 BURROUGHS WELLCOME CO,RES TRIANGLE PK,NC 27709. NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,RES TRIANGLE PK,NC 27709. NSI TECHNOL SERV CORP,RES TRIANGLE PK,NC. UNION CARBIDE CORP,BUSHY RUN RES CTR,EXPORT,PA. RP CROFTON, KM (reprint author), US EPA,HLTH EFFECTS RES LAB,DIV NEUROTOXICOL,MD-74B,RES TRIANGLE PK,NC 27711, USA. RI Crofton, Kevin/J-4798-2015 OI Crofton, Kevin/0000-0003-1749-9971 NR 65 TC 68 Z9 70 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD NOV-DEC PY 1991 VL 13 IS 6 BP 599 EP 609 DI 10.1016/0892-0362(91)90043-V PG 11 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA GW462 UT WOS:A1991GW46200005 PM 1779947 ER PT J AU ADAMS, EH AF ADAMS, EH TI PREVALENCE OF PRESCRIPTION DRUG-ABUSE - DATA FROM THE NATIONAL INSTITUTE ON DRUG-ABUSE SO NEW YORK STATE JOURNAL OF MEDICINE LA English DT Article C1 NATL INST DRUG ABUSE,BALTIMORE,MD. NR 4 TC 10 Z9 10 U1 0 U2 0 PU MED SOC STATE OF NY PI LAKE SUCCESS PA 420 LAKEVILLE RD P O BOX 5404, LAKE SUCCESS, NY 11042 SN 0028-7628 J9 NEW YORK STATE J MED PD NOV PY 1991 VL 91 IS 11 SU S BP S32 EP S36 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA GP420 UT WOS:A1991GP42000008 PM 1663221 ER PT J AU FULLER, EO HASSELMEYER, EG HUNTER, JC ABDELLAH, FG HINSHAW, AS AF FULLER, EO HASSELMEYER, EG HUNTER, JC ABDELLAH, FG HINSHAW, AS TI SUMMARY STATEMENTS OF THE NIH NURSING RESEARCH GRANT APPLICATIONS SO NURSING RESEARCH LA English DT Article AB Summary statements from the Nursing Research Study Section, Division of Research Grants, NIH, between October, 1986 and June, 1988 were used to identify reasons for recommending approval or disapproval of grant applications with RO1 and R29 activity codes. The 917 comments (25 +/- 4 per critique), sorted into one of nine categories (Aims, Significance, Investigator, Budget, Resources, Design, Sample, Techniques, Data Analysis) for analysis, were classified as Strengths (positive comments) or Weaknesses (negative comments). The weaknesses of approved applications were confined mostly to the categories of Design and Techniques. Disapproved applications had few strengths and many weaknesses in Design, Sample, Techniques, and Data Analysis. Critiques of First Award (R29) and traditional research project grant applications (RO1) were similar. The approved applications addressed meaningful problems, had well-synthesized literature reviews, and were solvable by available techniques. The research plans were consonant with stated aims, and the methods sections reflected understanding of the principles underlying the techniques to be used. A supportive environment and adequate research resources, including access to the study population were common to these applications. Disapproved applications provided poor synthesis of the literature, methods inconsistent with the aims, and often reflected inadequate understanding of techniques to be used. C1 NATL CTR NURSING RES,BETHESDA,MD. US PHS,ROCKVILLE,MD. RP FULLER, EO (reprint author), UNIV PENN,NURSING & PHYSIOL,PHILADELPHIA,PA 19104, USA. NR 8 TC 1 Z9 1 U1 1 U2 3 PU AMER J NURSING CO PI NEW YORK PA 555 W 57TH ST, NEW YORK, NY 10019-2961 SN 0029-6562 J9 NURS RES JI Nurs. Res. PD NOV-DEC PY 1991 VL 40 IS 6 BP 346 EP 351 PG 6 WC Nursing SC Nursing GA GT352 UT WOS:A1991GT35200005 PM 1956813 ER PT J AU GOLDENBERG, RL CLIVER, SP CUTTER, GR HOFFMAN, HJ CASSADY, G DAVIS, RO NELSON, KG AF GOLDENBERG, RL CLIVER, SP CUTTER, GR HOFFMAN, HJ CASSADY, G DAVIS, RO NELSON, KG TI BLACK-WHITE DIFFERENCES IN NEWBORN ANTHROPOMETRIC MEASUREMENTS SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID LOW BIRTH-WEIGHT; GESTATIONAL-AGE; NEONATAL-MORTALITY; RACIAL-DIFFERENCES; INFANT-MORTALITY; UNITED-STATES; RISK-FACTORS; PREGNANCY; SMOKING; FETAL AB The mean birth weight of black infants is consistently less than that of white infants. In 1518 low-income multiparous women, the mean difference in singleton births was 171 g, of which 38 g was partitioned to preterm births and another 35 g reflected lower gestational ages in term births. A series of regression analyses were used to determine the effect of black race on various newborn measurements in 1205 term newborns, adjusting for other known risk factors. In this model, black race accounted for a mean decrease of 148 g in weight and 0.52 cm in length. There were also significant decreases in mean head (0.44 cm), chest (0.66 cm), and abdominal (0.56 cm) circumferences. Arm and leg lengths were not different, but black arm circumferences (0.14 cm) were significantly larger. Triceps and thigh skin fold measurements were not statistically different, but black subscapular skin fold values were significantly smaller (0.17 mm). The ponderal index in blacks was significantly less than in whites. These data suggest that in this population, intrinsic and/or extrinsic factors associated with race account for most smaller black newborn measurements and for much of the racial difference in birth weight. C1 UNIV ALABAMA,DEPT PEDIAT,BIRMINGHAM,AL 35294. UNIV ALABAMA,SCH PUBL HLTH,BIRMINGHAM,AL 35294. NICHHD,PREVENT RES PROGRAM,BETHESDA,MD 20892. RP GOLDENBERG, RL (reprint author), UNIV ALABAMA,DEPT OBSTET & GYNECOL,PERINATAL EPIDEMIOL UNIT,UNIV STN,BIRMINGHAM,AL 35294, USA. FU NICHD NIH HHS [N01-HD-4-2811] NR 29 TC 35 Z9 35 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 1991 VL 78 IS 5 BP 782 EP 788 PN 1 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA GL669 UT WOS:A1991GL66900012 PM 1923197 ER PT J AU ASKEW, DS BARTHOLOMEW, C BUCHBERG, AM VALENTINE, MB JENKINS, NA COPELAND, NG IHLE, JN AF ASKEW, DS BARTHOLOMEW, C BUCHBERG, AM VALENTINE, MB JENKINS, NA COPELAND, NG IHLE, JN TI HIS-1 AND HIS-2 - IDENTIFICATION AND CHROMOSOMAL MAPPING OF 2 COMMONLY REARRANGED SITES OF VIRAL INTEGRATION IN A MYELOID-LEUKEMIA SO ONCOGENE LA English DT Article ID T-CELL LYMPHOMAS; C-MYB LOCUS; PROVIRAL INSERTION; PROMOTER INSERTION; RETROVIRAL INSERTION; TRANSCRIPTIONAL ACTIVATION; HOMEOBOX GENE; N-MYC; VIRUS; LINE AB To identify genes that contribute to myeloid leukemogenesis we have cloned viral integration sites from a CasBrM-MuLV-induced interleukin 3-independent myeloid leukemia cell line. Genomic probes derived from cellular sequences flanking two integrated proviruses were used to screen restriction digests of DNAs from a panel of 52 hematopoietic cell lines, 30 of which were established from CasBrM-MuLV- or MoMuLV-induced mouse leukemias. Probes from one integration site (His-1) defined a region that was rearranged in 3/52 cell lines, and probes from a second integration site (His-2) identified a rearrangement in 2/52 cell lines. Both cases of His-2 rearrangements occurred in concert with viral insertions in the His-1 locus. Genetic mapping of these loci using interspecific backcross analysis assigned the His-1 locus to mouse chromosome 2 and the His-2 locus to mouse chromosome 19. In situ hybridization with a probe from the human homologous region mapped the His-1 locus to human chromosome 2q14-q21. No recombinants were observed between His-2 and Gin-1, a common site of provirus integration in Gross passage A MuLV-induced T-cell leukemias, in 131 backcross animals, suggesting that these loci are tightly linked. The His-1 locus maps to mouse chromosome 2 distinct from any known oncogene or common site of integration but near the proximal breakpoint for a deletion that is observed in over 90% of radiation-induced leukemias. C1 ST JUDE CHILDRENS RES HOSP, DEPT BIOCHEM, MEMPHIS, TN 38105 USA. NCI, FREDERICK CANC RES & DEV CTR, MAMMALIAN GENET LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. ST JUDE CHILDRENS RES HOSP, DEPT HEMATOL ONCOL, MEMPHIS, TN 38105 USA. FU NCI NIH HHS [CA 51020, P30 CA21765, N01-CO-74101] NR 59 TC 37 Z9 37 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV PY 1991 VL 6 IS 11 BP 2041 EP 2047 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA GX119 UT WOS:A1991GX11900015 PM 1682866 ER PT J AU SACCHI, N WENDTNER, CM THIELE, CJ AF SACCHI, N WENDTNER, CM THIELE, CJ TI SINGLE-CELL DETECTION OF ETS-1 TRANSCRIPTS IN HUMAN NEUROECTODERMAL CELLS SO ONCOGENE LA English DT Note ID EWINGS-SARCOMA; DNA-BINDING; PROTOONCOGENE EXPRESSION; TRANSFORMING GENE; PROTO-ONCOGENES; SEQUENCE; PROTEINS; ERYTHROBLASTOSIS; LINES; NEUROEPITHELIOMA AB The genes of the ets family are thought to code for a novel class of transcriptional factors. These proteins have a specific DNA-binding domain different from the basic domain of both the helix-loop-helix and leucine zipper families of DNA-binding proteins. The ets-1 gene product has been shown to bind to the enhancer region of the human T-cell receptor alpha-gene during thymocyte ontogeny. This finding explains the high expression of ets-1 observed in T cells and the correlation between ets-1 expression and the expression of the T-cell receptor gene during fetal development. The ets-1 gene is also possibly biologically active in neural cells. By using RNA in situ hybridization analysis, we demonstrate the presence of ets-1 transcripts in cells of peripheral embryonal neuroectodermal tumors, specifically neuroepithelioma and neuroblastoma. In addition, the gene is found transcribed in Ewing's sarcoma, postulated to be ontogenetically related to tumors derived from the neural crest. C1 NCI,PEDIAT ONCOL BRANCH,MOLEC GENET LAB,BETHESDA,MD 20892. RP SACCHI, N (reprint author), NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702, USA. NR 45 TC 16 Z9 16 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV PY 1991 VL 6 IS 11 BP 2149 EP 2154 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA GX119 UT WOS:A1991GX11900028 PM 1945417 ER PT J AU GOTTSTEIN, B NASH, TE AF GOTTSTEIN, B NASH, TE TI ANTIGENIC VARIATION IN GIARDIA-LAMBLIA - INFECTION OF CONGENITALLY ATHYMIC NUDE AND SCID MICE SO PARASITE IMMUNOLOGY LA English DT Article DE ANTIGENIC VARIATION IN GIARDIA-LAMBLIA ID MURIS INFECTION AB Athymic nude mice of the outbred Zur:ICR-nu and inbred BALB/c strain and scid mice were infected with a cloned human isolate of Giardia lamblia (GS/M-83-H7). Changes in the expression of the major surface epitope of the intestinal trophozoites (characterized by the binding capacity of monoclonal antibody MoAb G10/4) as well as cellular and humoral immune parameters of the hosts were followed during the course of infection. Self-cure was observed in heterozygous (nu/+) BALB/c mice by day 22 post-infection (p.i.) and in heterozygous (nu/+) Zur:ICR-nu strain by day 65 p.i. Homozygous (nu/nu) mice of both strains remained chronically infected until end of the experiments (day 45 p.i. for BALB/c mice and day 122 p.i. for Zur:ICR-nu mice, respectively). Only heterozygous (nu/+) mice were able to mount a gut-associated (Peyer's patch) lymphoproliferative response to G. lamblia antigen. Therefore, T-cell dependent mechanisms were necessary for a self-cure. Antigenic variation occurred in all nu/+ and nu/nu animals of both strains. Trophozoites expressing the major surface epitope (assessed by direct immunofluorescence with FITC-labelled MoAb G10/4) decreased to zero by day 22 p.i. In contrast, the proportion of trophozoites expressing the major surface epitope in infected scid mice remained at the initial level (> 99%) until termination of the experiment (day 25 p.i.); therefore, antigenic variation did not occur. All nu/nu and nu/+ mice but not scid mice demonstrated a humoral immune response to G. lamblia antigen. These experiments suggest functional B-cell dependent mechanisms are most likely responsible for the surface antigen switch. Transfer of infection occurred naturally from experimentally infected scid-mice to their mother, proving the initial antigenic surface variant remains unchanged after encystment and subsequent excystment followed by infection in a new host. C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. RP GOTTSTEIN, B (reprint author), UNIV ZURICH,INST PARASITOL,WINTERTHURERSTR 266A,CH-8057 ZURICH,SWITZERLAND. NR 12 TC 37 Z9 37 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0141-9838 J9 PARASITE IMMUNOL JI Parasite Immunol. PD NOV PY 1991 VL 13 IS 6 BP 649 EP 659 DI 10.1111/j.1365-3024.1991.tb00560.x PG 11 WC Immunology; Parasitology SC Immunology; Parasitology GA GR632 UT WOS:A1991GR63200008 PM 1725820 ER PT J AU CALLAHAN, R GALLAHAN, D SMITH, G CROPP, C MERLO, G VENESIO, T LISCIA, D LIDEREAU, R AF CALLAHAN, R GALLAHAN, D SMITH, G CROPP, C MERLO, G VENESIO, T LISCIA, D LIDEREAU, R TI COMMON GENETIC PATHWAYS IN BREAST ONCOGENESIS SO PATHOLOGIE BIOLOGIE LA English DT Article DE MAMMARY TUMOR; INT GENES; BREAST CANCER; AMPLIFICATION; LOSS OF HETEROZYGOSITY; PROGNOSIS C1 SAN GIOVANNI VECCHIO HOSP,PATHOL SECT,I-10123 TURIN,ITALY. CTR RENE HUGUENIN,F-92211 ST CLOUD,FRANCE. RP CALLAHAN, R (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU EXPANSION SCI FRANCAISE PI PARIS PA 31 BLVD LATOUR MAUBOURG, 75007 PARIS, FRANCE SN 0369-8114 J9 PATHOL BIOL JI Pathol. Biol. PD NOV PY 1991 VL 39 IS 9 BP 910 EP 911 PG 2 WC Pathology SC Pathology GA GZ229 UT WOS:A1991GZ22900052 ER PT J AU ROILIDES, E MARSHALL, D VENZON, D BUTLER, K HUSSON, R PIZZO, PA AF ROILIDES, E MARSHALL, D VENZON, D BUTLER, K HUSSON, R PIZZO, PA TI BACTERIAL-INFECTIONS IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1-INFECTED CHILDREN - THE IMPACT OF CENTRAL VENOUS CATHETERS AND ANTIRETROVIRAL AGENTS SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE BACTERIAL INFECTIONS; HUMAN IMMUNODEFICIENCY VIRUS TYPE-1 INFECTION; CHILDREN ID IMMUNE-DEFICIENCY SYNDROME; AIDS-RELATED COMPLEX; ZIDOVUDINE; PERSPECTIVE; IMPAIRMENT; INVITRO; AZT AB We conducted a retrospective study to analyze the impact of central venous catheters (CVCs) and antiretroviral therapy on the frequency and the patterns of bacterial infections in children infected with human immunodeficiency virus during a 3-year period. Among 204 bacterial infections other than otitis media reviewed, soft tissue infection (n = 69), bacteremia (n = 57), pneumonia (n = 27) and sinusitis (n = 27) were encountered most frequently. Catheter-related staphylococcal infection was the most common infection in children with CVCs, particularly in those who were < 6 years old. In children without CVCs, Streptococcus pneumoniae was the most frequent organism. Younger children had more CVC-related infections whereas children with lower CD4 counts had more CVC-related and CVC-unrelated infections. A lower frequency of CVC-unrelated infections was detected in patients who received antiretroviral therapy, especially those receiving a continuous infusion of zidovudine. These data suggest that increased frequency and altered patterns of bacterial infections are associated with the use of CVCs in these patients, but antiretroviral therapy may reduce the frequency of CVC-unrelated infections. C1 NCI,PEDIAT BRANCH,INFECT DIS SECT,BLDG 10,RM 13N240,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 26 TC 39 Z9 40 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD NOV PY 1991 VL 10 IS 11 BP 813 EP 819 DI 10.1097/00006454-199111000-00004 PG 7 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA GP048 UT WOS:A1991GP04800005 PM 1661003 ER PT J AU BALIS, FM BLANEY, SM POPLACK, DG AF BALIS, FM BLANEY, SM POPLACK, DG TI ANTIRETROVIRAL DRUG DEVELOPMENT AND CLINICAL-PHARMACOLOGY SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE ACQUIRED IMMUNODEFICIENCY SYNDROME; RETROVIRUS; ANTIRETROVIRAL DRUGS; ZIDOVADINE; DIDEOXYINOSINE; CHILDREN ID HUMAN IMMUNODEFICIENCY VIRUS; AIDS-RELATED COMPLEX; PHASE-I TRIAL; 2',3'-DIDEOXYINOSINE DDI; CEREBROSPINAL-FLUID; ANTIVIRAL THERAPY; ZIDOVUDINE AZT; RENAL-DISEASE; PHARMACOKINETICS; INFECTION C1 WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. RP BALIS, FM (reprint author), NCI,PEDIAT BRANCH,BLDG 10,ROOM 13N240,BETHESDA,MD 20892, USA. NR 38 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD NOV PY 1991 VL 10 IS 11 BP 849 EP 857 DI 10.1097/00006454-199111000-00012 PG 9 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA GP048 UT WOS:A1991GP04800013 PM 1661004 ER PT J AU MAJANE, EA YANG, HYT AF MAJANE, EA YANG, HYT TI MAMMALIAN FMRF-NH2-LIKE PEPTIDE IN RAT PITUITARY - DECREASE BY OSMOTIC STIMULUS SO PEPTIDES LA English DT Article DE FMRF-NH2-LIKE; F-8-F-NH2; PITUITARY; HYPEROSMOTIC STIMULI; AVP; COREGULATION ID FMRFAMIDE-LIKE IMMUNOREACTIVITY; MORPHINE MODULATING PEPTIDE; CENTRAL NERVOUS-SYSTEM; SPINAL-CORD; BRATTLEBORO RAT; BRAIN; FLFQPQRF-NH2; VASOPRESSIN; FLFQPQRFAMIDE; NEUROPEPTIDES AB Previous studies with the Brattleboro rat suggested a possible interaction at the pituitary level between AVP and the neuropeptide, F-8-F-NH2. In order to test this hypothesis, we studied the effect of various osmotic stimuli on neurohypophyseal F-8-F-NH2. In rats drinking 2% NaCl solution for two days, neural lobe AVP and F-8-F-NH2 levels were equally reduced by 87%. After maximal depletion, pituitary levels of F-8-F-NH2 and AVP rebounded in parallel when normal drinking water was reintroduced. Pituitary stalk transection depleted neurohypophyseal F-8-F-NH2. The results of this study suggest that neurohypophyseal F-8-F-NH2 originates from the hypothalamus and, furthermore, is coreleased along with AVP in response to hyperosmotic stimuli. C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,BIOCHEM GENET LAB,WASHINGTON,DC 20032. NR 29 TC 36 Z9 36 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0196-9781 J9 PEPTIDES JI Peptides PD NOV-DEC PY 1991 VL 12 IS 6 BP 1303 EP 1308 DI 10.1016/0196-9781(91)90211-7 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA GW101 UT WOS:A1991GW10100022 PM 1815217 ER PT J AU GARRY, MG KAJANDER, KC BENNETT, GJ SEYBOLD, VS AF GARRY, MG KAJANDER, KC BENNETT, GJ SEYBOLD, VS TI QUANTITATIVE AUTORADIOGRAPHIC ANALYSIS OF [I-125] HUMAN CGRP BINDING-SITES IN THE DORSAL HORN OF RAT FOLLOWING CHRONIC CONSTRICTION INJURY OR DORSAL RHIZOTOMY SO PEPTIDES LA English DT Article DE CGRP; CHRONIC CONSTRICTION INJURY; DORSAL RHIZOTOMY; BINDING SITES; DORSAL HORN ID GENE-RELATED PEPTIDE; PRIMARY AFFERENT-FIBERS; CENTRAL NERVOUS-SYSTEM; SPINAL-CORD; SUBSTANCE-P; PERIPHERAL MONONEUROPATHY; RESPONSES; NEURONS; BRAIN; PAIN AB Quantitative receptor autoradiography was used to examine the binding of [I-125]-human CGRP in the dorsal horn of the L4 spinal segment of rats with a chronic constriction injury (CCI) of the sciatic nerve or unilateral dorsal rhizotomies of spinal segments L1-L6. At the times selected for study, we found no change in the amount of CGRP binding in any areas examined following CCI. In contrast, our results showed a temporally related increase in the amount of CGRP binding in areas within laminae I-II and in lateral lamina V of the dorsal horn ipsilateral to the rhizotomies. These results indicate that CGRP binding sites are regulated, most likely, by changes in the release of CGRP. Further, our results suggest that the release of CGRP from primary afferent neurons is unchanged in animals with a CCI. C1 UNIV MINNESOTA,DEPT CELL BIOL & NEUROANAT,4-135 JACKSON HALL,MINNEAPOLIS,MN 55455. NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. NR 32 TC 15 Z9 15 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0196-9781 J9 PEPTIDES JI Peptides PD NOV-DEC PY 1991 VL 12 IS 6 BP 1365 EP 1373 DI 10.1016/0196-9781(91)90221-A PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA GW101 UT WOS:A1991GW10100032 PM 1667690 ER PT J AU KOHN, EC AF KOHN, EC TI INVASION AND METASTASIS - BIOLOGY AND CLINICAL POTENTIAL SO PHARMACOLOGY & THERAPEUTICS LA English DT Review ID BASEMENT-MEMBRANE COLLAGEN; AUTOCRINE MOTILITY FACTOR; HUMAN-MELANOMA CELLS; BREAST-CANCER-CELLS; TUMOR-CELLS; GROWTH-FACTOR; PLASMINOGEN-ACTIVATOR; LAMININ RECEPTOR; EXTRACELLULAR-MATRIX; MONOCLONAL-ANTIBODY AB Metastatic dissemination of tumor is the primary cause of death for most cancer patients. The expanding field of study of the metastatic cascade has been the source of novel approaches to the diagnosis and treatment of cancer. The metastatic process involves angiogenesis, tumor cell adhesion to vascular basement membrane, local proteolysis to create an opening in the basement membrane, migration through that rent and into the secondary site, and finally, successful proliferation. Important components of the metastatic cascade such as basement membrane structures, adhesion molecules and their receptors, proteolytic enzymes, migration-inducing factors, and growth factors have been demonstrated to have reproducible patterns in malignant and metastatic tissues. These patterns have led to clinical correlations demonstrating their utility in the identification and follow-up of malignant and metastatic disease. In addition, several promising new anti-cancer drugs such as inhibitors of angiogenesis, protease-inhibitors, and blockers of signal transduction have been identified and are awaiting introduction into the clinical arena. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. RP KOHN, EC (reprint author), NCI,MED BRANCH,BETHESDA,MD 20892, USA. NR 91 TC 23 Z9 24 U1 0 U2 0 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. PD NOV PY 1991 VL 52 IS 2 BP 235 EP 244 DI 10.1016/0163-7258(91)90011-A PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HM561 UT WOS:A1991HM56100008 PM 1818338 ER PT J AU PENG, CK HAVLIN, S SCHWARTZ, M STANLEY, HE WEISS, GH AF PENG, CK HAVLIN, S SCHWARTZ, M STANLEY, HE WEISS, GH TI ALGEBRAICALLY DECAYING NOISE IN A SYSTEM OF PARTICLES WITH HARD-CORE INTERACTIONS SO PHYSICA A LA English DT Article ID RANDOM VELOCITY-FIELDS; ANOMALOUS DIFFUSION; ENHANCED DIFFUSION; DISORDERED MEDIA AB We record and analyze the noise experienced by a tracer particle in a one-dimensional system of particles interacting with hard-core interactions. We find that the correlations of the noise are long-range, with an algebraic decay in time. C1 BOSTON UNIV,DEPT PHYS,BOSTON,MA 02215. NIH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20892. TEL AVIV UNIV,DEPT PHYS & ASTRON,IL-69978 TEL AVIV,ISRAEL. RP PENG, CK (reprint author), BOSTON UNIV,CTR POLYMER STUDIES,BOSTON,MA 02215, USA. RI Peng, Chung-Kang/E-1489-2011 OI Peng, Chung-Kang/0000-0003-3666-9833 NR 14 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 J9 PHYSICA A JI Physica A PD NOV 1 PY 1991 VL 178 IS 3 BP 401 EP 405 DI 10.1016/0378-4371(91)90028-B PG 5 WC Physics, Multidisciplinary SC Physics GA GQ770 UT WOS:A1991GQ77000001 ER PT J AU SAGER, PR AF SAGER, PR TI WORKSHOP ON THE ROLE OF THE PLACENTA IN HIV-INFECTION AND THERAPY, NANTUCKET, MASSACHUSETTS, 10-13 SEPTEMBER 1990 SO PLACENTA LA English DT Editorial Material RP SAGER, PR (reprint author), NIAID,DIV AIDS,BASIC RES & DEV PROGRAM,DEV THERAPEUT BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0143-4004 J9 PLACENTA JI Placenta PD NOV-DEC PY 1991 VL 12 IS 6 BP 669 EP 672 DI 10.1016/0143-4004(91)90501-6 PG 4 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA HB159 UT WOS:A1991HB15900010 PM 1687162 ER PT J AU RAZIUDDIN MIKOVITS, JA CALVERT, I GHOSH, S KUNG, HF RUSCETTI, FW AF RAZIUDDIN MIKOVITS, JA CALVERT, I GHOSH, S KUNG, HF RUSCETTI, FW TI NEGATIVE REGULATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 EXPRESSION IN MONOCYTES - ROLE OF THE 65-KDA PLUS 50-KDA NF-KAPPA-B DIMER SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE RETROVIRAL TRANSCRIPTION; MONOCYTE ACTIVATION ID TUMOR NECROSIS FACTOR; LONG TERMINAL REPEAT; DNA-BINDING ACTIVITY; TRANSCRIPTION FACTOR; GENE-EXPRESSION; NUCLEAR FACTOR; FACTOR-ALPHA; CELL-LINE; ACTIVATION; INFECTION AB Although monocytic cells can provide a reservoir for viral production in vivo, their regulation of human immunodeficiency virus type 1 (HIV-1) transcription can be either latent, restricted, or productive. These differences in gene expression have not been molecularly defined. In THP-1 cells With restricted HIV expression, there is an absence of DNA-protein binding complex formation with the HIV-1 promoter-enhancer associated with markedly less viral RNA production. This absence of binding was localized to the NF-kappa-B region of the HIV-1 enhancer; the 65-kDa plus 50-kDa NF-kappa-B heterodimer was preferentially lost. Adding purified NF-kappa-B protein to nuclear extracts from cells with restricted expression overcomes this lack of binding. In addition, treatment of these nuclear extracts with sodium deoxycholate restored their ability to form the heterodimer, suggesting the presence of an inhibitor of Nf-kappa-B activity. Furthermore, treatment of nuclear extracts from these cells that had restricted expression with lipopolysaccharide increased viral production and NF-kappa-B activity. Antiserum specific for NF-kappa-B binding proteins, but not c-rel-specific antiserum, disrupted heterodimer complex formation. Thus, both NF-kappa-B-binding complexes are needed for optimal viral transcription. Binding of the 65-kDa plus 50-kDa heterodimer to the HIV-1 enhancer can be negatively regulated in monocytes, providing one mechanism restricting HIV-1 gene expression. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,BIOCHEM PHARMACOL LAB,FREDERICK,MD 21702. WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. PROGRAM RESOURCES INC,DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74102] NR 40 TC 6 Z9 6 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV PY 1991 VL 88 IS 21 BP 9426 EP 9430 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GM781 UT WOS:A1991GM78100011 PM 1946356 ER PT J AU MORRISON, A BELL, JB KUNKEL, TA SUGINO, A AF MORRISON, A BELL, JB KUNKEL, TA SUGINO, A TI EUKARYOTIC DNA-POLYMERASE AMINO-ACID-SEQUENCE REQUIRED FOR 3'-] 5' EXONUCLEASE ACTIVITY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE YEAST DNA POLYMERASE-II; MUTATOR PHENOTYPE; PROOFREADING; PROTEIN DOMAIN; DNA REPLICATION ID SITE-SPECIFIC MUTAGENESIS; HIGHLY CONSERVED REGION; SACCHAROMYCES-CEREVISIAE; YEAST; GENE; ALPHA; PURIFICATION; IDENTIFICATION; RECOGNITION; RESISTANCE AB We have identified an amino-proximal sequence motif, Phe-Asp-Ile-Glu-Thr, in Saccharomyces cerevisiae DNA polymerase II that is almost identical to a sequence comprising part of the 3' --> 5' exonuclease active site of Escherichia coli DNA polymerase I. Similar motifs were identified by amino acid sequence alignment in related, aphidicolin-sensitive DNA polymerases possessing 3' --> 5' proofreading exonuclease activity. Substitution of Ala for the Asp and Glu residues in the motif reduced the exonuclease activity of partially purified DNA polymerase II at least 100-fold while preserving the polymerase activity. Yeast strains expressing the exonuclease-deficient DNA polymerase II had on average about a 22-fold increase in spontaneous mutation rate, consistent with a presumed proofreading role in vivo. In multiple amino acid sequence alignments of this and two other conserved motifs described previously, five residues of the 3' --> 5' exonuclease active site of E. coli DNA polymerase I appeared to be invariant in aphidicolin-sensitive DNA polymerases known to possess 3' --> 5' proofreading exonuclease activity. None of these residues, however, appeared to be identifiable in the catalytic subunits of human, yeast, or Drosophila alpha-DNA polymerases. RP MORRISON, A (reprint author), NIEHS,MOLEC GENET LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 33 TC 217 Z9 218 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV PY 1991 VL 88 IS 21 BP 9473 EP 9477 DI 10.1073/pnas.88.21.9473 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GM781 UT WOS:A1991GM78100021 PM 1658784 ER PT J AU BRAY, P LICHTER, P THIESEN, HJ WARD, DC DAWID, IB AF BRAY, P LICHTER, P THIESEN, HJ WARD, DC DAWID, IB TI CHARACTERIZATION AND MAPPING OF HUMAN GENES ENCODING ZINC FINGER PROTEINS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TRANSCRIPTION; CHROMOSOME; SEQUENCE-TAGGED SITE ID TRANSCRIPTION FACTOR-IIIA; INSITU HYBRIDIZATION; HUMAN CHROMOSOME-11; MULTIGENE FAMILY; XENOPUS-LAEVIS; DNA LIBRARIES; HUMAN GENOME; 5S RNA; KRUPPEL; DIFFERENTIATION AB The zinc finger motif, exemplified by a segment of the Drosophila gap gene Kruppel, is a nucleic acid-binding domain present in many transcription factors. To investigate the gene family encoding this motif in the human genome, a placental genomic library was screened at moderate stringency with a degenerate oligodeoxynucleotide probe designed to hybridize to the His/Cys (H/C) link region between adjoining zinc fingers. Over 200 phage clones were obtained and are being sorted into groups by partial sequencing, cross-hybridization with oligodeoxynucleotide probes, and PCR amplification. Further, the genomic clones were cross-hybridized with a set of 30 zinc finger-encoding cDNAs (Kox1-Kox30) isolated from a human T-cell cDNA library. Four cDNAs (Kox4, Kox7, Kox12, and Kox15) were identified that match one or more genomic clones; these matches were confirmed by nucleotide sequence analysis. One or more clones from each locus were mapped onto human metaphase chromosomes by chromosomal in situ suppression hybridization with fluorescent probe detection. We mapped ZNF7/Kox4 to chromosome 8qter, ZNF19/Kox12 to 16q22, ZNF22/Kox15 to 10q11, and ZNF44/Kox7 to 16p11. The results of these analyses support the conclusion that the human genome contains many, probably several hundred, zinc finger genes with consensus H/C link regions. C1 YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06520. BASEL INST IMMUNOL,CH-4005 BASEL,SWITZERLAND. DEUTSCH KREBSFORSCHUNGSZENTRUM,W-6900 HEIDELBERG,GERMANY. RP BRAY, P (reprint author), NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892, USA. NR 31 TC 57 Z9 62 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV PY 1991 VL 88 IS 21 BP 9563 EP 9567 DI 10.1073/pnas.88.21.9563 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GM781 UT WOS:A1991GM78100039 PM 1946370 ER PT J AU COLLINS, PL MINK, MA STEC, DS AF COLLINS, PL MINK, MA STEC, DS TI RESCUE OF SYNTHETIC ANALOGS OF RESPIRATORY SYNCYTIAL VIRUS GENOMIC RNA AND EFFECT OF TRUNCATIONS AND MUTATIONS ON THE EXPRESSION OF A FOREIGN REPORTER GENE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NEGATIVE-STRAND VIRUS; TRANSFECTION; VIRAL PROMOTER; MUTAGENESIS; INFECTIOUS RNA ID RECOMBINANT VACCINIA VIRUS; INFLUENZA-VIRUS; POLYMERASE AB The viral genomic RNA (vRNA) of human respiratory syncytial virus is a nonsegmented negative strand that is not infectious alone. To develop methods for complementing synthetic vRNA with viral proteins, a cDNA was constructed to encode a vRNA in which all of the viral protein-coding sequences were removed and replaced with a negative-sense copy of the bacterial chloramphenicol acetyltransferase gene. Upon transfection into respiratory syncytial virus-infected cells, the synthetic vRNA was "rescued" such that it was amplified, expressed, and packaged into infectious virions. A heterologous paramyxovirus, parainfluenza virus 3, was inactive in rescue. Further internal deletions mapped the cis-acting viral sequences required for rescue to two segments totaling 105 nucleotides (nt) derived from the two vRNA ends. Rescue was unaffected by replacement of the 44-nt 3'-terminal leader region with a 50-nt sequence that is complementary to the 5' terminus and represents the 3' end of the positive-sense replicative intermediate RNA. This 5'-end complement was related to the parental leader region only near the 3' terminus (91% or 73% identical for the first 11 or 22 nt, respectively). The addition of 11 heterologous nt to the 3' end of the parental leader region ablated rescue, suggesting that the 3'-proximal conserved domain is required and cannot function from an internal site. However, deletion of the 3'-terminal 3 nt, or a double transition at positions 4 and 5, had no effect on rescue. Thus, the 3'-terminal 5 nt, although conserved between 3' ends of the negative- and positive-sense RNAs, do not appear to be essential. RP COLLINS, PL (reprint author), NIAID,INFECT DIS LAB,BLDG 7,ROOM 100,BETHESDA,MD 20892, USA. NR 19 TC 119 Z9 120 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV PY 1991 VL 88 IS 21 BP 9663 EP 9667 DI 10.1073/pnas.88.21.9663 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GM781 UT WOS:A1991GM78100059 PM 1946383 ER PT J AU SHAFER, GE EMERY, DW GUSTAFSSON, K GERMANA, S ANDERSON, WF SACHS, DH LEGUERN, C AF SHAFER, GE EMERY, DW GUSTAFSSON, K GERMANA, S ANDERSON, WF SACHS, DH LEGUERN, C TI EXPRESSION OF A SWINE CLASS-II GENE IN MURINE BONE-MARROW HEMATOPOIETIC-CELLS BY RETROVIRAL-MEDIATED GENE-TRANSFER SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MAJOR HISTOCOMPATIBILITY COMPLEX; DR BETA-GENE; RETROVIRAL VECTOR ID LONG-TERM EXPRESSION; STEM-CELLS; MINIATURE SWINE; HLA-DR; ADENOSINE-DEAMINASE; NUCLEOTIDE-SEQUENCE; CHAIN GENE; VECTORS; CDNA; ANTIGEN AB As a first step in assessing the efficacy of a gene transfer approach to the induction of transplantation tolerance in our miniature swine model, double-copy retroviral vectors engineered to express a drug-resistance marker (neomycin) and a swine class II DRB cDNA were constructed. Infectious particles containing these vectors were produced at a titer of > 1 x 10(6) G418-resistant colony-forming units/ml using both ecotropic and amphotropic packaging cell lines. Flow cytometric analysis of DRA-transfected murine fibroblasts subsequently transduced with virus-containing supernatants demonstrated that the transferred sequences were sufficient to produce DR surface expression. Cocultivation of murine bone marrow with high-titer producer lines leads to the transduction of 40% of granulocyte/macrophage colony-forming units (CFU-GM) as determined by the frequency of colony formation under G418 selection. After nearly 5 weeks in long-term bone marrow culture, virus-exposed marrow still contained G418-resistant CFU-GM at a frequency of 25%. In addition, virtually all of the transduced and selected colonies contained DRB-specific transcripts. These results suggest that a significant proportion of very primitive myelopoietic precursor cells can be transduced with the DRB recombinant vector and that vector sequences are expressed in the differentiated progeny of these cells. C1 MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,BLDG 149,13TH ST,BOSTON,MA 02129. NCI,DIV CANC BIOL DIAG & CTR,IMMUNOL BRANCH,TRANSPLANTAT BIOL SECT,BETHESDA,MD 20892. NR 30 TC 24 Z9 24 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV PY 1991 VL 88 IS 21 BP 9760 EP 9764 DI 10.1073/pnas.88.21.9760 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GM781 UT WOS:A1991GM78100081 PM 1946400 ER PT J AU PANTALEO, G GRAZIOSI, C BUTINI, L PIZZO, PA SCHNITTMAN, SM KOTLER, DP FAUCI, AS AF PANTALEO, G GRAZIOSI, C BUTINI, L PIZZO, PA SCHNITTMAN, SM KOTLER, DP FAUCI, AS TI LYMPHOID ORGANS FUNCTION AS MAJOR RESERVOIRS FOR HUMAN-IMMUNODEFICIENCY-VIRUS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE VIRAL BURDEN; PERIPHERAL BLOOD; POLYMERASE CHAIN REACTION ID POLYMERASE CHAIN-REACTION; PERIPHERAL-BLOOD; T-CELL; HIV-1 INFECTION; VIRAL-ANTIGENS; NODES; AIDS; LYMPHADENOPATHY; EXPRESSION; TISSUE AB The total number of human immunodeficiency virus type 1 (HIV-1)-infected circulating CD4+ T lymphocytes is considered to be a reflection of the HIV burden at any given time during the course of HIV infection. However, the low frequency of HIV-infected circulating CD4+ T lymphocytes and the low level or absence of plasma viremia in the early stages of infection do not correlate with the progressive immune dysfunction characteristic of HIV infection. In this study, we have determined whether HIV-infected circulating CD4+ T lymphocytes are a correct reflection of the total pool of HIV-infected CD4+ T cells (i.e., HIV burden). To this end, HIV burden has been comparatively analyzed in peripheral blood and lymphoid tissues (lymph nodes, adenoids, and tonsils) from the same patients. The presence of HIV-1 DNA in mononuclear cells isolated simultaneously from peripheral blood and lymphoid tissues of the same patients was determined by polymerase chain reaction amplification. We found that the frequency of HIV-1-infected cells in unfractionated or sorted CD4+ cell populations isolated from lymphoid tissues was significantly higher (0.5-1 log10 unit) than the frequency in peripheral blood. Comparable results were obtained in five HIV seropositive patients in the early stages of disease and in one patient with AIDS. These results demonstrate that a heavy viral load does reside in the lymphoid organs, indicating that they may function as major reservoirs for HIV. In addition, the finding of a heavy viral load in the lymphoid organs of patients in the early stages of disease may explain the progressive depletion of CD4+ T lymphocytes and the immune dysfunction associated with the early stages of HIV infection. C1 NCI,PEDIAT BRANCH,DIV CANC TREATMENT,BETHESDA,MD 20892. ST LUKES ROOSEVELT HOSP,NEW YORK,NY 10025. RP PANTALEO, G (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM 11B-13,BETHESDA,MD 20892, USA. RI Pantaleo, Giuseppe/K-6163-2016 NR 28 TC 408 Z9 410 U1 2 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV PY 1991 VL 88 IS 21 BP 9838 EP 9842 DI 10.1073/pnas.88.21.9838 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GM781 UT WOS:A1991GM78100097 PM 1682922 ER PT J AU BLAKE, MJ UDELSMAN, R FEULNER, GJ NORTON, DD HOLBROOK, NJ AF BLAKE, MJ UDELSMAN, R FEULNER, GJ NORTON, DD HOLBROOK, NJ TI STRESS-INDUCED HEAT-SHOCK PROTEIN-70 EXPRESSION IN ADRENAL-CORTEX - AN ADRENOCORTICOTROPIC HORMONE-SENSITIVE, AGE-DEPENDENT RESPONSE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MESSENGER-RNA; CORTICOSTERONE RESPONSES; INDUCTION; CELLS; RATS; PROMOTER; BINDING; BRAIN; GENE; ACTH AB The induction of heat shock proteins (HSP) by cellular stress and the activation of the hypothalamic-pituitary-adrenal axis by physiologic stress are biological responses that aid in the maintenance of cellular and organismal homeostasis, respectively. In this report, restraint stress, known to activate the hypothalamic-pituitary-adrenal axis, is shown to induce expression of HSP70 mRNA selectively in the adrenal cortex of the rat. Restraint-induced HSP70 expression in the adrenals is rapid and is preceded by the activation of a protein factor capable of binding to the heat shock transcriptional control element. The ability of restraint to induce HSP70 expression in the adrenal is virtually eliminated in hypophysectomized rats but can be restored by the exogenous administration of adrenocorticotropic hormone. The magnitude of this induction declines as a function of increasing age, which may contribute to a reduced stress tolerance by aged animals. These results support a role for HSP70 in the physiologic stress response mediated by the hypothalamic-pituitary-adrenal axis. C1 NIA,GERONTOL RES CTR,MOLEC GENET LAB,4940 EASTERN AVE,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV HOSP,DEPT SURG,BALTIMORE,MD 21205. NR 45 TC 173 Z9 177 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV PY 1991 VL 88 IS 21 BP 9873 EP 9877 DI 10.1073/pnas.88.21.9873 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GM781 UT WOS:A1991GM78100104 PM 1658790 ER PT J AU DECLUE, JE COHEN, BD LOWY, DR AF DECLUE, JE COHEN, BD LOWY, DR TI IDENTIFICATION AND CHARACTERIZATION OF THE NEUROFIBROMATOSIS TYPE-1 PROTEIN PRODUCT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GTPASE-ACTIVATING PROTEIN; CYCLIC-AMP PATHWAY; SACCHAROMYCES-CEREVISIAE; RAS PROTEINS; GENE-PRODUCT; MAMMALIAN GAP; CELLS; PHOSPHORYLATION; INDUCTION; MEMBRANE AB The neurofibromatosis type 1 (NF1) gene responsible for von Recklinghausen neurofibromatosis is related to regulators of ras proteins, and a portion of NF1 that is homologous to the ras GTPase-activating protein (GAP) encodes a similar GTPase-stimulating activity. We have raised rabbit antisera to a bacterially synthesized 48-kDa peptide corresponding to the GAP-related domain of NF1 (NFI-GRD). These antisera immunoprecipitated the NF1-GRD peptide, and one of them specifically inhibited the GTPase-stimulating activity of NF1-GRD. The sera specifically detected a 280-kDa protein in lysates of mouse NIH 3T3 and human HeLa cells. This protein corresponds to the NF1 gene product, as shown by several criteria, including partial proteolysis. Subcellular fractionation revealed that while GAP is predominantly cytoplasmic, all of the NF1 was recovered in a pellet (100,000 x g) fraction. NF1 was present in a large molecular mass complex in fibroblast and Schwannoma cell lines and appears to associate with a very large (400-500 kDa) protein in both cell types. The relevance of these findings to cellular regulation of p21ras is discussed. RP DECLUE, JE (reprint author), NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892, USA. NR 36 TC 142 Z9 143 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV PY 1991 VL 88 IS 22 BP 9914 EP 9918 DI 10.1073/pnas.88.22.9914 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GP895 UT WOS:A1991GP89500002 PM 1946460 ER PT J AU NAKAYAMA, T SAMELSON, LE NAKAYAMA, Y MUNITZ, TI SHEARD, M JUNE, CH SINGER, A AF NAKAYAMA, T SAMELSON, LE NAKAYAMA, Y MUNITZ, TI SHEARD, M JUNE, CH SINGER, A TI LIGAND-STIMULATED SIGNALING EVENTS IN IMMATURE CD4+CD8+ THYMOCYTES EXPRESSING COMPETENT T-CELL RECEPTOR COMPLEXES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MONOCLONAL-ANTIBODY; SURFACE EXPRESSION; IMPARTS REACTIVITY; TRANSGENIC MICE; ANTIGEN; DETERMINANT; CD4; TOLERANCE; RESPONSES; MOLECULE AB During thymic selection of the developing T-cell repertoire, the fate of individual CD4+CD8+ thymocytes is determined by the specificity of the T-cell antigen receptors (TCRs) they express. Paradoxically, most CD4+CD8+ thymocytes express few TCR molecules, and those they express are essentially incapable of transducing intracellular signals as measured by intracellular calcium mobilization. However, both TCR number and calcium-signaling capability are significantly induced in CD4+CD8+ thymocytes when the cells are released from intrathymic inhibitory signals that are mediated by their CD4 molecules. Here, the response to ligand engagement of TCR on "induced" CD4+CD8+ thymocytes that have been released from CD4-mediated inhibition was examined and was found to result in internalization of surface TCR complexes and rephosphorylation of zeta-chains of the TCR complex. In addition, a proportion of induced CD4+CD8+ thymocytes were found to fragment their DNA upon ligand engagement. Thus, this study describes early events in immature CD4+CD8+ thymocytes resulting from TCR-mediated signals. C1 NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B-17,BETHESDA,MD 20892. NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. NIDDKD,MOLEC CELLULAR NUTR ENDOCRINOL BRANCH,BETHESDA,MD 20892. USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20814. RI Nakayama, Toshinori/E-1067-2017 NR 28 TC 35 Z9 35 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV PY 1991 VL 88 IS 22 BP 9949 EP 9953 DI 10.1073/pnas.88.22.9949 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GP895 UT WOS:A1991GP89500009 PM 1719558 ER PT J AU WILKIE, TM SCHERLE, PA STRATHMANN, MP SLEPAK, VZ SIMON, MI AF WILKIE, TM SCHERLE, PA STRATHMANN, MP SLEPAK, VZ SIMON, MI TI CHARACTERIZATION OF G-PROTEIN ALPHA-SUBUNITS IN THE G(Q) CLASS - EXPRESSION IN MURINE TISSUES AND IN STROMAL AND HEMATOPOIETIC-CELL LINES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HETEROTRIMERIC GTP-BINDING PROTEIN; SIGNAL TRANSDUCTION; MULTIGENE FAMILY; PHOSPHOLIPASE-C ID BINDING REGULATORY PROTEINS; CHAIN; REARRANGEMENT; DIVERSITY; TUMORS; GENES; HEAVY AB Murine G-alpha-14 and G-alpha-15 cDNAs encode distinct alpha-subunits of heterotrimeric guanine nucleotide-binding proteins (G proteins). These alpha-subunits are related to members of the G(q) class and share certain sequence characteristics with G-alpha(q), G-alpha-11, and G-alpha-16, such as the absence of a pertussis toxin ADP-ribosylation site. G-alpha-11 and G-alpha(q) are ubiquitously expressed among murine tissues but G-alpha-14 is predominantly expressed in spleen, lung, kidney, and testis whereas G-alpha-15 is primarily restricted to hematopoietic lineages. Among hematopoietic cell lines, G-alpha-11 mRNA is found in all cell lines tested, G-alpha(q) is expressed widely but is not found in most T-cell lines, G-alpha-15 is predominantly expressed in myeloid and B-cell lineages, and G-alpha-14 is expressed in bone marrow adherent (stromal) cells, certain early myeloid cells, and progenitor B cells. Polyclonal antisera produced from synthetic peptides that correspond to two regions of G-alpha-15 react with a protein of 42 kDa expressed in B-cell membranes and in Escherichia coli transformed with G-alpha-15 cDNA. The expression patterns that were observed in mouse tissues and cell lines indicate that each of the alpha-subunits in the G(q) class may be involved in pertussis toxin-insensitive signal-transduction pathways that are fundamental to hematopoietic cell differentiation and function. C1 CALTECH,DIV BIOL 14775,PASADENA,CA 91125. NIH,METAB BRANCH,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM11576, GM34236] NR 37 TC 249 Z9 251 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV PY 1991 VL 88 IS 22 BP 10049 EP 10053 DI 10.1073/pnas.88.22.10049 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GP895 UT WOS:A1991GP89500030 PM 1946421 ER PT J AU KAPTAIN, S DOWNEY, WE TANG, C PHILPOTT, C HAILE, D ORLOFF, DG HARFORD, JB ROUAULT, TA KLAUSNER, RD AF KAPTAIN, S DOWNEY, WE TANG, C PHILPOTT, C HAILE, D ORLOFF, DG HARFORD, JB ROUAULT, TA KLAUSNER, RD TI A REGULATED RNA-BINDING PROTEIN ALSO POSSESSES ACONITASE ACTIVITY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE IRON; FERRITIN; TRANSLATIONAL REGULATION; IRON-RESPONSIVE ELEMENT; IRON-RESPONSIVE ELEMENT BINDING PROTEIN ID IRON-RESPONSIVE ELEMENT; FERRITIN MESSENGER-RNA; TRANSFERRIN RECEPTOR; CHELATABLE IRON; 4FE-4S CLUSTER; HEAVY-SUBUNIT; GENE; IDENTIFICATION; CHROMOSOME-9; CLONING AB A clone for the iron-responsive element (IRE)-binding protein (IRE-BP) has been transfected and expressed in mouse fibroblasts. The IRE-BP gene product binds IREs with high affinity and specificity. Amino acid alignments reveal that the IRE-BP is 30% identical to mitochondrial aconitase. The 18 active site residues of mitochondrial aconitase are identical to those in the IRE-BP, suggesting that the IRE-BP may possess aconitase activity. After purification of native IRE-BP and immunoaffinity purification of transfected and expressed IRE-BP, we demonstrate that the purified IRE-BP has aconitase activity. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. NR 26 TC 170 Z9 170 U1 2 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV PY 1991 VL 88 IS 22 BP 10109 EP 10113 DI 10.1073/pnas.88.22.10109 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GP895 UT WOS:A1991GP89500042 PM 1946430 ER PT J AU BURTON, DR BARBAS, CF PERSSON, MAA KOENIG, S CHANOCK, RM LERNER, RA AF BURTON, DR BARBAS, CF PERSSON, MAA KOENIG, S CHANOCK, RM LERNER, RA TI A LARGE ARRAY OF HUMAN MONOCLONAL-ANTIBODIES TO TYPE-1 HUMAN-IMMUNODEFICIENCY-VIRUS FROM COMBINATORIAL LIBRARIES OF ASYMPTOMATIC SEROPOSITIVE INDIVIDUALS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE AIDS; ANTIBODY REPERTOIRES; PASSIVE IMMUNIZATION; FILAMENTOUS PHAGE; PHAGE SURFACE EXPRESSION ID MATERNAL ANTIBODIES; GLYCOPROTEIN GP120; AFFINITY; CHIMPANZEES AB A panel of human monoclonal antibody Fab fragments has been generated against the surface glycoprotein gp120 of type 1 human immunodeficiency virus (HIV) by antigen selection from a random combinatorial library expressed on the surface of filamentous phage. The library was prepared from 5 ml of bone marrow from an asymptomatic individual who has been HIV-positive for 6 years. The antibodies have high affinity for antigen (mostly with affinity constants of > 10(8) M-1) and notable sequence diversity. Given appropriate donor selection, the methods described should allow the generation of antibodies for the evaluation of passive immunization as a therapy for AIDS. C1 SCRIPPS RES INST, DEPT CHEM, LA JOLLA, CA 92037 USA. NIAID, INFECT DIS LAB, BETHESDA, MD 20892 USA. UNIV SHEFFIELD, KREBS INST, DEPT MOLEC BIOL & BIOTECHNOL, SHEFFIELD S10 2TN, S YORKSHIRE, ENGLAND. KAROLINSKA INST, KARALINSKA HOSP, DEPT MED, S-10401 STOCKHOLM 60, SWEDEN. RP BURTON, DR (reprint author), SCRIPPS RES INST, DEPT MOLEC BIOL, 10666 N TORREY PINES RD, LA JOLLA, CA 92037 USA. FU NIMH NIH HHS [IP50 MH47680] NR 24 TC 530 Z9 545 U1 3 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV PY 1991 VL 88 IS 22 BP 10134 EP 10137 DI 10.1073/pnas.88.22.10134 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GP895 UT WOS:A1991GP89500047 PM 1719545 ER PT J AU PIETENPOL, JA MUNGER, K HOWLEY, PM STEIN, RW MOSES, HL AF PIETENPOL, JA MUNGER, K HOWLEY, PM STEIN, RW MOSES, HL TI FACTOR-BINDING ELEMENT IN THE HUMAN C-MYC PROMOTER INVOLVED IN TRANSCRIPTIONAL REGULATION BY TRANSFORMING GROWTH-FACTOR BETA-1 AND BY THE RETINOBLASTOMA GENE-PRODUCT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NEGATIVE GROWTH FACTOR; TUMOR SUPPRESSOR GENE; PROTOONCOGENES ID TGF-BETA-1 INHIBITION; SUSCEPTIBILITY GENE; EXPRESSION; KERATINOCYTES; PROLIFERATION; SUPPRESSION; PROTEINS; SEQUENCE; MURINE; CELLS AB Previous studies have shown that transforming growth factor beta-1 (TGF-beta-1) inhibition of keratinocyte proliferation involves suppression of c-myc transcription, and indirect evidence has suggested that the retinoblastoma gene product (pRB) may be involved in this process. In this study, transient expression of pRB in skin keratinocytes was shown to repress transcription of the human c-myc promoter as effectively as TGF-beta-1. The same c-myc promoter region was required for regulation by both TGF-beta-1 and pRB. These sequences, termed the TGF-beta control element (TCE), lie between positions -86 and -63 relative to the P1 transcription start site. Oligonucleotides containing the TCE bound to several nuclear factors in mobility-shift assays using extracts from cells with or without normal pRB. Binding of some factors was inhibited by TGF-beta-1 treatment of TGF-beta-sensitive but not TGF-beta-insensitive cells. These data indicate that pRB can suppress c-myc transcription and suggest the involvement of cellular factors in addition to pRB in the TGF-beta-1 pathway for the inhibition of c-myc transcription and growth inhibition. C1 VANDERBILT UNIV,MED CTR,SCH MED,DEPT MOLEC PHYSIOL & BIOPHYS,NASHVILLE,TN 37232. NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892. RP PIETENPOL, JA (reprint author), VANDERBILT UNIV,MED CTR,SCH MED,DEPT CELL BIOL,NASHVILLE,TN 37232, USA. FU NCI NIH HHS [CA-42572, CA-48799]; NIGMS NIH HHS [GM-30257] NR 21 TC 124 Z9 124 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV PY 1991 VL 88 IS 22 BP 10227 EP 10231 DI 10.1073/pnas.88.22.10227 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GP895 UT WOS:A1991GP89500066 PM 1946442 ER PT J AU GAHM, SJ FOWLKES, BJ JAMESON, SC GASCOIGNE, NRJ COTTERMAN, MM KANAGAWA, O SCHWARTZ, RH MATIS, LA AF GAHM, SJ FOWLKES, BJ JAMESON, SC GASCOIGNE, NRJ COTTERMAN, MM KANAGAWA, O SCHWARTZ, RH MATIS, LA TI PROFOUND ALTERATION IN AN ALPHA-BETA T-CELL ANTIGEN RECEPTOR REPERTOIRE DUE TO POLYMORPHISM IN THE 1ST COMPLEMENTARITY-DETERMINING REGION OF THE BETA-CHAIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ALLELIC POLYMORPHISM; T-CELL ANTIGEN RECOGNITION ID 3-DIMENSIONAL STRUCTURE; CLONAL DELETION; MOLECULAR-BASIS; GENE SEGMENTS; CYTOCHROME-C; SELF-MHC; COMPLEX; RECOGNITION; SELECTION; SPECIFICITY AB Amino acid residues that are critical in maintaining the framework structure of immunoglobulin heavy- and light-chain variable (V) regions are strongly conserved in the V-alpha and V-beta-proteins of the alpha-beta T-cell antigen receptor (TCR-alpha-beta). Consequently, it has been proposed that TCR-alpha-beta has a conformation similar to that of an immunoglobulin Fab fragment and that the regions of the TCR homologous to the three immunoglobulin complementarity-determining regions (CDRS 1, 2, and 3) bind to the peptide antigen-major histocompatibility complex (MHC) molecule ligand. A single amino acid substitution in the predicted CDR1 of the V-beta-3 protein of certain mouse strains dramatically altered TCR-alpha-beta usage in an antigen-specific MHC-restricted immune response but did not abrogate V-beta-3 specificity for the superantigens minor lymphocyte stimulatory locus (Mls)c and staphylococcal enterotoxin A (SEA). The results confirm the importance of the V-beta CDR1 in antigen-MHC molecule recognition, supporting the Fab-like structural model of TCR-alpha-beta, and provide further evidence that conventional antigen-MHC recognition and superantigen recognition are mediated by distinct regions of the TCR-beta-chain. They also suggest that allelic polymorphism may be a significant source of diversity in the TCR repertoire. C1 NIAID, HOWARD HUGHES MED INST, NIH RES SCHOLARS PROGRAM, BETHESDA, MD 20892 USA. NIAID, CELLULAR & MOLEC IMMUNOL LAB, BETHESDA, MD 20892 USA. Scripps Res Inst, RES INST, DEPT IMMUNOL, LA JOLLA, CA 92037 USA. WASHINGTON UNIV, SCH MED, DEPT PATHOL, ST LOUIS, MO 63110 USA. RP GAHM, SJ (reprint author), NCI, FREDERICK CANC RES & DEV CTR, BIOL RESPONSE MODIFIERS PROGRAM, FREDERICK, MD 21702 USA. RI Jameson, Stephen/D-9892-2013 FU NIGMS NIH HHS [GM-39476] NR 36 TC 33 Z9 33 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV PY 1991 VL 88 IS 22 BP 10267 EP 10271 DI 10.1073/pnas.88.22.10267 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GP895 UT WOS:A1991GP89500074 PM 1835090 ER PT J AU TAKAHASHI, K DAI, LC FUERST, TR BIDDISON, WE EARL, PL MOSS, B ENNIS, FA AF TAKAHASHI, K DAI, LC FUERST, TR BIDDISON, WE EARL, PL MOSS, B ENNIS, FA TI SPECIFIC LYSIS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1-INFECTED CELLS BY A HLA-A3.1-RESTRICTED CD8+ CYTOTOXIC LYMPHOCYTE-T CLONE THAT RECOGNIZES A CONSERVED PEPTIDE SEQUENCE WITHIN THE GP41 SUBUNIT OF THE ENVELOPE PROTEIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE AIDS; T-CELL EPITOPE ID CYTO-TOXIC RESPONSES; FINE SPECIFICITY; INDIVIDUALS; MOLECULE; ANTIGENS; INVIVO; HLA-A3; BLOOD; AIDS AB A HLA-A3.1-restricted CD8+ cytotoxic T-cell clone, E7.20, that lyses cells infected with human immunodeficiency virus type 1 was isolated from an infected individual. The epitope was localized to amino acids 768-778 (RLRDLLLIVTR, NL43 env sequence) of the cytoplasmic domain of gp41 by successive use of a panel of recombinant vaccinia viruses that express truncated env genes and synthetic peptides. The epitope is conserved on 7 (NL43, BRU, HXB2, BRVA, SC, JH3, and JFL) of 13 human immunodeficiency virus type 1 isolates from North America. Synthetic peptides of this region of strains RF and CDC4 are also recognized by E7.20 despite a nonconservative Thr --> Val or Thr --> Ala change at amino acid 777; however, an MN peptide, which has four amino acid substitutions, was not reactive. The epitope recognized by E7.20 has a predicted hydrophobic alpha-helical structure, with three contiguous Leu residues followed by Ile and Val at amino acids 772-776. Cytotoxicity was restricted by HLA-A3.1 using allogeneic target cells that shared HLA class I antigens with the donor and an HLA-A and -B negative human plasma cell line transfected with the HLA-A3.1 gene. The transfected cells were infectable by human immunodeficiency virus type 1 strains IIIB and MN but only the former virus sensitized them to killing by E7.20. The ability of E7.20 to specifically lyse a human lymphocyte line infected with a human immunodeficiency virus type 1 strain carrying the conserved epitope is consistent with an important role for cytotoxic T cells in controlling infection. C1 UNIV MASSACHUSETTS,MED CTR,DEPT MED,DIV INFECT DIS,WORCESTER,MA 01655. NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. FU NIAID NIH HHS [T32-AI07272, UO1-AI2648, R01-AI24750] NR 31 TC 50 Z9 50 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV PY 1991 VL 88 IS 22 BP 10277 EP 10281 DI 10.1073/pnas.88.22.10277 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GP895 UT WOS:A1991GP89500076 PM 1719555 ER PT J AU REDDY, MR VISWANADHAN, VN WEINSTEIN, JN AF REDDY, MR VISWANADHAN, VN WEINSTEIN, JN TI RELATIVE DIFFERENCES IN THE BINDING FREE-ENERGIES OF HUMAN IMMUNODEFICIENCY VIRUS-1 PROTEASE INHIBITORS - A THERMODYNAMIC CYCLE-PERTURBATION APPROACH SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SYNTHETIC HIV-1 PROTEASE; MOLECULAR-DYNAMICS; CRYSTAL-STRUCTURE; SIMULATION; DESIGN; WATER; POTENTIALS; HYDRATION; COMPLEXES; SOLVATION AB Peptidomimetic inhibitors of the human immunodeficiency virus 1 protease show considerable promise for treatment of AIDS. We have, therefore, been seeking computer-assisted drug design methods to aid in the systematic design of such inhibitors from a lead compound. Here we report thermodynamic cycle-perturbation calculations (using molecular dynamics simulations) to compute the relative difference in free energy of binding that results when one entire residue (valine) is deleted from one such inhibitor. In particular, we studied the "alchemic" mutation of the inhibitor Ac-Ser-Leu-Asn-(Phe-Hea-Pro)-Ile-Val-OMe (SI) to Ac-Ser-Leu-Asn-(Phe-Hea-Pro)-Ile-OMe (S2), where Hea is hydroxyethylamine, in two different (R and S) diastereomeric configurations of the hydroxyethylene group. The calculated (averaged for R and S) difference in binding free energy [3.3 +/- 1.1 kcal/mol (mean +/- SD); 1 cal = 4.184 J] is in good agreement with the experimental value of 3.8 +/- 1.3 kcal/mol, obtained from the measured K(i) values for an equilibrium mixture of R and S configurations. Precise testing of our predictions will be possible when binding data become available for the two disastereomers separately. The observed binding preference for S1 is explained by the stronger ligand-protein interaction, which dominates an opposing contribution arising from the large desolvation penalty of S1 relative to S2. This calculation suggests that the thermodynamic cycle-perturbation approach can be useful even when a relatively large change in the ligand is simulated and supports the use of the thermodynamic cycle-perturbation algorithm for screening proposed derivatives of a lead inhibitor/drug prior to their synthesis. C1 NCI,MATH BIOL LAB,BETHESDA,MD 20892. RP REDDY, MR (reprint author), AGOURON PHARMACEUT INC,3565 GEN ATOM COURT,SAN DIEGO,CA 92121, USA. NR 33 TC 61 Z9 61 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV PY 1991 VL 88 IS 22 BP 10287 EP 10291 DI 10.1073/pnas.88.22.10287 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GP895 UT WOS:A1991GP89500078 PM 1946447 ER PT J AU BRAY, M LAI, CJ AF BRAY, M LAI, CJ TI CONSTRUCTION OF INTERTYPIC CHIMERIC DENGUE VIRUSES BY SUBSTITUTION OF STRUCTURAL PROTEIN GENES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CHIMERA; VIRAL PROTEINS; NEUROVIRULENCE ID NUCLEOTIDE-SEQUENCE; VACCINE; GENOME; IMMUNOGENICITY; VOLUNTEERS; CLEAVAGE; REQUIRES; RNA; NS1 AB Dengue virus contains an 11-kilobase positive-strand RNA genome that codes for, in one open reading frame, three structural proteins (capsid, premembrane, and envelope), followed by seven nonstructural proteins. The structural protein genes of a full-length cDNA clone of type 4 dengue virus were replaced with the corresponding genes of dengue 1 or dengue 2 to create intertypic chimeric cDNA. The RNA transcripts made from these templates were infectious when transfected into permissive cells in culture. Progeny of chimeric cDNA produced apparently authentic dengue 1 or dengue 2 structural proteins, together with dengue 4 nonstructural proteins, and as a consequence exhibited type 1 or type 2 serological specificity. Both of the chimeras ultimately grew to the same titer as their type 1 or type 2 parent, but the type 2/type 4 chimera grew very slowly. This chimera also produced small plaques; in contrast, the type 1/type 4 chimera produced normal size plaques. The type 2/type 4 chimera retained the mouse neurovirulence of the dengue 2 virus, which was the source of its structural protein genes. Each of the mice inoculated intracerebrally with the chimera died, but survival time was prolonged. The retardation of replication of the type 2/type 4 chimeric virus suggests that this virus and possibly other intertypic dengue virus chimeras with similar properties should be examined for attenuation in primates and possible usefulness in a live dengue virus vaccine for humans. RP BRAY, M (reprint author), NIAID,INFECT DIS LAB,MOLEC VIRAL BIOL SECT,BETHESDA,MD 20892, USA. NR 22 TC 94 Z9 101 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV PY 1991 VL 88 IS 22 BP 10342 EP 10346 DI 10.1073/pnas.88.22.10342 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GP895 UT WOS:A1991GP89500089 PM 1682924 ER PT J AU ANDERSON, WW ARNOLD, J BALDWIN, DG BECKENBACH, AT BROWN, CJ BRYANT, SH COYNE, JA HARSHMAN, LG HEED, WB JEFFERY, DE KLACZKO, LB MOORE, BC PORTER, JM POWELL, JR PROUT, T SCHAEFFER, SW STEPHENS, JC TAYLOR, CE TURNER, ME WILLIAMS, GO MOORE, JA AF ANDERSON, WW ARNOLD, J BALDWIN, DG BECKENBACH, AT BROWN, CJ BRYANT, SH COYNE, JA HARSHMAN, LG HEED, WB JEFFERY, DE KLACZKO, LB MOORE, BC PORTER, JM POWELL, JR PROUT, T SCHAEFFER, SW STEPHENS, JC TAYLOR, CE TURNER, ME WILLIAMS, GO MOORE, JA TI 4 DECADES OF INVERSION POLYMORPHISM IN DROSOPHILA-PSEUDOOBSCURA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE EVOLUTION; GENETIC CHANGE; CHROMOSOME INVERSIONS ID NATURAL-POPULATIONS; ALLELE PROBABILITY; STATISTICS AB We report data that continue the studies of Dobzhansky and others on the frequencies of third-chromosome inversions in natural populations of Drosophila pseudoobscura in North America. The common gene arrangements continue to be present in frequencies similar to those described four decades ago, and the broad geographic patterns also remain unchanged. There is only one pronounced trend over time: the increase in frequency of the Tree Line inversion in Pacific coast populations. C1 UNIV CALIF RIVERSIDE,DEPT BIOL,RIVERSIDE,CA 92521. UNIV GEORGIA,DEPT GENET,ATHENS,GA 30602. UNIV ARIZONA,DEPT ECOL & EVOLUT,TUCSON,AZ 85721. SIMON FRASER UNIV,DEPT BIOL SCI,BURNABY V5A 1S6,BC,CANADA. CALIF STATE POLYTECH UNIV POMONA,DEPT BIOL,POMONA,CA 91768. UNIV CHICAGO,DEPT ECOL & EVOLUT,CHICAGO,IL 60637. UNIV CALIF DAVIS,DEPT GENET,DAVIS,CA 95616. BRIGHAM YOUNG UNIV,DEPT ZOOL,PROVO,UT 84602. YALE UNIV,DEPT BIOL,NEW HAVEN,CT 06511. UNIV CALIF LOS ANGELES,DEPT BIOL,LOS ANGELES,CA 90024. UNIV AKRON,DEPT BIOL,AKRON,OH 44325. UNIV ESTADUAL CAMPINAS,DEPT GENET,BR-13100 CAMPINAS,SP,BRAZIL. PENN STATE UNIV,DEPT BIOL,UNIV PK,PA 16802. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. RI Klaczko, Louis/D-5412-2009; Schaeffer, Stephen/B-1662-2010; OI Klaczko, Louis/0000-0002-4737-1365; Schaeffer, Stephen/0000-0003-2070-5342 FU NIGMS NIH HHS [GM38462] NR 11 TC 54 Z9 56 U1 2 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV PY 1991 VL 88 IS 22 BP 10367 EP 10371 DI 10.1073/pnas.88.22.10367 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GP895 UT WOS:A1991GP89500094 PM 1946458 ER PT J AU SACKS, LV LABRIOLA, AM GILL, VJ GORDIN, FM AF SACKS, LV LABRIOLA, AM GILL, VJ GORDIN, FM TI USE OF CIPROFLOXACIN FOR SUCCESSFUL ERADICATION OF BACTEREMIA DUE TO CAMPYLOBACTER-CINAEDI IN A HUMAN-IMMUNODEFICIENCY-VIRUS INFECTED PERSON SO REVIEWS OF INFECTIOUS DISEASES LA English DT Article AB A 36-year-old homosexual man who was infected with human immunodeficiency virus presented with a 2-month history of fever and intermittent diarrhea. Stool cultures were negative for bacterial pathogens, ova, parasites, and acid-fast organisms. An initial blood culture became positive after 5 days for a curved, gram-negative rod that was identified later as Campylobacter cinaedi. The patient received a series of antibiotic regimens, including a 2-week course of erythromycin followed by a 2-week course of tetracycline, but follow-up blood cultures continued to yield C. cinaedi. The patient was then treated with a 2-week course of oral ciprofloxacin; he remained asymptomatic 11 weeks later, at which time a blood culture was negative for C. cinaedi. To the best of our knowledge, this is the first documented case of symptomatic bacteremia due to C. cinaedi that was successfully treated with ciprofloxacin. C1 NIH,MICROBIOL SERV,BETHESDA,MD 20892. RP SACKS, LV (reprint author), VET AFFAIRS MED CTR,DEPT INFECT DIS,50 IRVING ST NW,WASHINGTON,DC 20422, USA. NR 7 TC 33 Z9 33 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0162-0886 J9 REV INFECT DIS PD NOV-DEC PY 1991 VL 13 IS 6 BP 1066 EP 1068 PG 3 WC Immunology; Microbiology SC Immunology; Microbiology GA GT753 UT WOS:A1991GT75300006 PM 1775838 ER PT J AU FREEDMAN, DO AF FREEDMAN, DO TI EXPERIMENTAL-INFECTION OF HUMAN-SUBJECTS WITH STRONGYLOIDES SPECIES SO REVIEWS OF INFECTIOUS DISEASES LA English DT Article ID STERCORALIS; PRISONERS; WAR AB Because of excellent and readily available animal models of infection with Stronglyloides species, much of the basic biology of the parasite was understood by the early 1930s. Only selected issues of major physiologic importance were left to be addressed by intentional human infections. Concern about the strongyloides hyperinfection syndrome and the parasite's characteristic refractoriness to drug therapy led investigators of experimental human infections to act as subjects. This article reviews studies that describe experimental human infection with Strongyloides stercoralis and Strongyloides fullebroni as well as other Strongyloides species. These studies address two main issues: the clinical manifestations associated with the prepatent and early patent phases of infection, and the development of immunity to reinfection in individuals previously infected. The possible conclusions from these studies are discussed in the context of the current understanding of natural human and experimental animal infections. C1 NIH,INFECT DIS LAB,BETHESDA,MD 20892. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. RP FREEDMAN, DO (reprint author), UNIV ALABAMA,DIV GEOGR MED,1025 18TH ST S,BIRMINGHAM,AL 35205, USA. NR 26 TC 17 Z9 17 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0162-0886 J9 REV INFECT DIS PD NOV-DEC PY 1991 VL 13 IS 6 BP 1221 EP 1226 PG 6 WC Immunology; Microbiology SC Immunology; Microbiology GA GT753 UT WOS:A1991GT75300028 PM 1775856 ER PT J AU ALLEN, WP HITCHCOCK, PJ AF ALLEN, WP HITCHCOCK, PJ TI HERPES-SIMPLEX VIRUS-VACCINE WORKSHOP, BETHESDA, MARYLAND 31 JULY 1 AUGUST 1989 - PREFACE SO REVIEWS OF INFECTIOUS DISEASES LA English DT Editorial Material RP ALLEN, WP (reprint author), NIAID,DIV MICROBIOL & INFECT DIS,BETHESDA,MD 20892, USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0162-0886 J9 REV INFECT DIS PD NOV-DEC PY 1991 VL 13 SU 11 BP S891 EP S891 PG 1 WC Immunology; Microbiology SC Immunology; Microbiology GA GV626 UT WOS:A1991GV62600001 ER PT J AU ROONEY, JF WOHLENBERG, CR MOSS, B NOTKINS, AL AF ROONEY, JF WOHLENBERG, CR MOSS, B NOTKINS, AL TI LIVE VACCINIA VIRUS RECOMBINANTS EXPRESSING HERPES-SIMPLEX VIRUS GENES SO REVIEWS OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT WORKSHOP ON HERPES SIMPLEX VIRUS VACCINE CY JUL 31-AUG 01, 1989 CL BETHESDA, MD SP NIAID, NIAID, MICROBIOL & INFECTIOUS DIS PROGRAM ID TYPE-1 GLYCOPROTEIN-D; IMMUNODEFICIENT MICE; INFECTION; IMMUNITY; PROTECTION; VECTORS; NEUTRALIZATION; CONSTRUCTION; POXVIRUSES; MECHANISMS AB Vaccinia virus recombinants expressing antigens from herpes simplex virus (HSV) have been tested as potential live virus vaccines for prevention of HSV infection. We describe three vaccinia virus/HSV recombinants. The first expresses the HSV-1 glycoprotein D (vaccinia/gD), the second expresses the HSV-1 glycoprotein B (vaccinia/gB), and the third expresses both the HSV-1 glycoprotein D and the influenza A hemagglutinin (vaccinia/HSVgD/influenza). Mice immunized with vaccinia/gD or vaccinia/gB developed antibodies capable of neutralizing HSV in vitro and were protected against both lethal and latent infection with HSV. Protection against HSV challenge persisted for > 1 year in mice immunized with vaccinia/gD. The immune response to HSV in mice immunized with vaccinia/gD could be increased by a booster vaccination with vaccinia/gD. However, the immune response to HSV was decreased in animals immunized with a vaccinia recombinant that expressed non-HSV genes before vaccination with vaccinia/gD. In separate experiments, a bivalent vaccinia recombinant, vaccinia/HSVgD/influenza, was constructed and was found to be comparable to the vaccinia/gD single recombinant in immunogenicity and protective efficacy against lethal HSV challenge. We conclude that vaccinia/HSV recombinants can provide protection against HSV infection in mice and that these recombinants may provide an alternative approach in the development of a live virus vaccine against HSV. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. RP ROONEY, JF (reprint author), NIDR,ORAL MED LAB,BLDG 30,ROOM 230,BETHESDA,MD 20892, USA. NR 20 TC 5 Z9 5 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0162-0886 J9 REV INFECT DIS PD NOV-DEC PY 1991 VL 13 SU 11 BP S898 EP S903 PG 6 WC Immunology; Microbiology SC Immunology; Microbiology GA GV626 UT WOS:A1991GV62600004 PM 1664124 ER PT J AU LIPNICK, RN TSOKOS, GC MAGILAVY, DB AF LIPNICK, RN TSOKOS, GC MAGILAVY, DB TI IMMUNE ABNORMALITIES IN THE PATHOGENESIS OF JUVENILE RHEUMATOID-ARTHRITIS SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; TUMOR NECROSIS FACTOR; GROWTH-FACTOR-BETA; COLONY-STIMULATING FACTOR; RECOMBINANT INTERLEUKIN 1-ALPHA; CHRONIC INFLAMMATORY ARTHRITIS; MIXED LYMPHOCYTE-REACTION; POSITIVE T-CELLS; PERIPHERAL-BLOOD; B-CELLS C1 GEORGE WASHINGTON UNIV,SCH MED,DEPT PEDIAT,WASHINGTON,DC 20052. CHILDRENS NATL MED CTR,DIV RHEUMATOL,WASHINGTON,DC. NIH,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT MED,BETHESDA,MD 20814. NIDDKD,METAB DIS BRANCH,BETHESDA,MD. UNIV CHICAGO,DEPT PEDIAT,CHICAGO,IL 60637. LA RABIDA CHILDRENS HOSP & RES CTR,DIV RHEUMATOL,CHICAGO,IL. RES INST,CHICAGO,IL. NR 96 TC 11 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD NOV PY 1991 VL 17 IS 4 BP 843 EP 857 PG 15 WC Rheumatology SC Rheumatology GA LA274 UT WOS:A1991LA27400003 PM 1767077 ER PT J AU GUY, HR DURELL, SR WARMKE, J DRYSDALE, R GANETZKY, B AF GUY, HR DURELL, SR WARMKE, J DRYSDALE, R GANETZKY, B TI SIMILARITIES IN AMINO-ACID-SEQUENCES OF DROSOPHILA-EAG AND CYCLIC NUCLEOTIDE-GATED CHANNELS SO SCIENCE LA English DT Article ID SODIUM-CHANNEL; ALIGNMENT; TOOL C1 UNIV WISCONSIN,GENET LAB,MADISON,WI 53706. RP GUY, HR (reprint author), NCI,MATH BIOL LAB,BETHESDA,MD 20892, USA. NR 20 TC 99 Z9 101 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 1 PY 1991 VL 254 IS 5032 BP 730 EP 730 DI 10.1126/science.1658932 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GN474 UT WOS:A1991GN47400048 PM 1658932 ER PT J AU GU, JR JIANG, HQ HE, LP LI, DZ ZHOU, XM DAI, WL QIAN, LF CHEN, YQ SCHWEINFEST, C PAPAS, T AF GU, JR JIANG, HQ HE, LP LI, DZ ZHOU, XM DAI, WL QIAN, LF CHEN, YQ SCHWEINFEST, C PAPAS, T TI TRANSTHYRETIN (PREALBUMIN) GENE IN HUMAN PRIMARY HEPATIC CANCER SO SCIENCE IN CHINA SERIES B-CHEMISTRY LA English DT Article DE HEPATOMA; SUBTRACTING CDNA LIBRARY; SUPPRESSION; DELETION ID RETINOBLASTOMA; SEQUENCE; CLONING AB From a subtracting cDNA library constructed from normal liver versus human primary hepatic cancer (PHC), a cDNA clone pG8 was isolated. Using it as a probe, RNA extracted from one human liver and 9 PHC samples were analyzed by Northern hybridization. As expected, its mRNA was highly expressed in liver; however, the expression was strikingly suppressed in PHC. Only weak signal was observed in 2 out of 9 PHC, while no signal was detectable in the other 7 samples. Utilizing pG8 as a probe, DNA from the same PHC specimens was analyzed after MspI digestion and Southern hybridization. Deletion of DNA fragment was observed in 4 out of 9 samples. In further study of cancer and non-cancerous liver from other 7 PHC patients, similar deletion of DNA fragments in cancer was observed in 4 out of 7 samples. After sequencing of the clone of 572 bp, it was unexpectedly found that pG8 was completely homologous to the coding sequence of transthyretin, TTR gene, as TTR (or prealbumin) gene has been known to be linked to a hereditary disorder, familial amyloidosis (FAP), and related to thyroxine transport and binding to retinol-RBP (the retinol binding protein) complex. This is the first report of a study on TTR in human primary hepatic cancer. Since TTR gene was strikingly suppressed in mRNA expression and possibly defective in its gene structure, it was strongly implicated that TTR might be an important gene marker or a candidate of anti-oncogene for human PHC. The biological activity of TTR gene is under study. C1 NCI,FREDRICK CANC RES & DEV CTR,MOLEC ONCOL LAB,FREDERICK,MD 21701. RP GU, JR (reprint author), SHANGHAI CANC INST,NATL LAB ONCOGENES & RELATED GENES,SHANGHAI 200032,PEOPLES R CHINA. NR 8 TC 7 Z9 10 U1 1 U2 1 PU SCIENCE CHINA PRESS PI BEIJING PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA SN 1001-652X J9 SCI CHINA SER B JI Sci. China Ser. B-Chem. PD NOV PY 1991 VL 34 IS 11 BP 1312 EP 1318 PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA GY892 UT WOS:A1991GY89200005 PM 1666289 ER PT J AU BENICHOU, J AF BENICHOU, J TI METHODS OF ADJUSTMENT FOR ESTIMATING THE ATTRIBUTABLE RISK IN CASE-CONTROL STUDIES - A REVIEW SO STATISTICS IN MEDICINE LA English DT Article AB In the 1980's, progress was made in adjusting estimates of the attributable risk (AR) for confounding factors and in calculating associated confidence intervals. In this paper, methods of adjustment for estimation of the AR in case-control studies are reviewed. The limitations and problems associated with two methods based on stratification, the weighted-sum approach and the Mantel-Haenszel approach, are discussed. They include small-sample bias with the weighted-sum approach and the difficulty of taking interaction into account with the Mantel-Haenszel approach. A third method based on logistic regression is reviewed. It is argued that this latter method has the greatest generality and flexibility, and includes the two other approaches as special cases. Throughout the paper, an example of a case-control study of oesophageal cancer illustrates the use of the methods described. RP BENICHOU, J (reprint author), NCI,6130 EXECUT BLVD,EPN 403,ROCKVILLE,MD 20892, USA. NR 0 TC 95 Z9 98 U1 2 U2 6 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV PY 1991 VL 10 IS 11 BP 1753 EP 1773 DI 10.1002/sim.4780101113 PG 21 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA GU267 UT WOS:A1991GU26700011 PM 1845304 ER PT J AU WYSOCKI, RJ SIDDIQUI, MA BARCHI, JJ DRISCOLL, JS MARQUEZ, VE AF WYSOCKI, RJ SIDDIQUI, MA BARCHI, JJ DRISCOLL, JS MARQUEZ, VE TI A MORE EXPEDIENT APPROACH TO THE SYNTHESIS OF ANTI-HIV-ACTIVE 2,3-DIDEOXY-2-FLUORO-BETA-D-THREO-PENTOFURANOSYL NUCLEOSIDES SO SYNTHESIS-STUTTGART LA English DT Article ID ANALOGS AB Starting with 1,3,5-tri-O-benzoyl-2-deoxy-2-fluoro-alpha-D-arabinofuranose, a versatile method for the synthesis of 2,3-dideoxy-2-fluoro-beta-D-threo-pentofuranosyl nucleosides is described and illustrated with the synthesis of 9-(2,3-dideoxy-2-fluoro-beta-D-threo-pentofuranosyl)adenine and 1-(2,3-dideoxy-2-fluoro-beta-D-threo-pentofuranosyl)cytosine. In this approach, the deoxygenation of the 3'-OH function is performed at the sugar stage of the synthesis prior to coupling with the purine or pyrimidine base. C1 NCI,DTP,DCT,MED CHEM LAB,BETHESDA,MD 20892. RI Barchi Jr., Joseph/N-3784-2014 NR 11 TC 30 Z9 30 U1 0 U2 0 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0039-7881 J9 SYNTHESIS-STUTTGART JI Synthesis PD NOV PY 1991 IS 11 BP 1005 EP 1008 PG 4 WC Chemistry, Organic SC Chemistry GA GR367 UT WOS:A1991GR36700028 ER PT J AU BURKE, TR RUSS, P LIM, B AF BURKE, TR RUSS, P LIM, B TI PREPARATION OF 4-[BIS(TERT-BUTOXY)PHOSPHORYLMETHYL]-N-(FLUOREN-9-YLMETHOXYCARBONYL)-DL- PHENYLALANINE - A HYDROLYTICALLY STABLE ANALOG OF O-PHOSPHOTYROSINE POTENTIALLY SUITABLE FOR PEPTIDE-SYNTHESIS SO SYNTHESIS-STUTTGART LA English DT Article ID ACIDS AB Sodium methoxide catalyzed aldol condensation of ethyl alpha-azidoacetate with 4-[bis-(tert-butoxy)phosphorylmethyl]benzaldehyde (4) provides methyl alpha-azido-4-[bis(tert-butoxy)phosphorymethyl]cinnamate (5), which undergoes facile hydrogenation in the presence of 10% palladium on carbon to yield methyl 4-[bis(tert-butoxy)phosphorylmethyl]-DL-phenylalaninate (6). Hydrolysis of the methyl ester by brief treatment with 1 N sodium hydroxide in dioxane, followed by reaction with 1-benzotriazolyl 9-fluorenylmethyl carbonate (Fmoc-OBT) at pH 8 cleanly provides 4-[bis(tert-butoxy)phosphorylmethyl]-N-Fmoc-DL-phenylalanine (3), an orthogonally protected derivative potentially suitable for utilization in the synthesis of peptides containing a hydrolytically stable mimetic of O-phosphotyrosine. RP BURKE, TR (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BLDG 37,RM5C06,BETHESDA,MD 20892, USA. RI Burke, Terrence/N-2601-2014 NR 13 TC 35 Z9 35 U1 0 U2 1 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0039-7881 J9 SYNTHESIS-STUTTGART JI Synthesis PD NOV PY 1991 IS 11 BP 1019 EP 1020 PG 2 WC Chemistry, Organic SC Chemistry GA GR367 UT WOS:A1991GR36700033 ER PT J AU GHOSH, D AF GHOSH, D TI NEW DEVELOPMENTS OF A TRANSCRIPTION FACTORS DATABASE SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID PROTEINS; COMPILATION; ALIGNMENT; TOOL RP GHOSH, D (reprint author), NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894, USA. NR 24 TC 52 Z9 52 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD NOV PY 1991 VL 16 IS 11 BP 445 EP 447 DI 10.1016/0968-0004(91)90173-S PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GT333 UT WOS:A1991GT33300013 PM 1776175 ER PT J AU MERCHENTHALER, I AF MERCHENTHALER, I TI CURRENT STATUS OF BRAIN HYPOPHYSIOTROPIC FACTORS - MORPHOLOGICAL ASPECTS SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID MEDIAN-EMINENCE; CONTAINING NEURONS; IMMUNOHISTOCHEMICAL IDENTIFICATION; PARAVENTRICULAR NUCLEUS; RAT; VASOPRESSIN; RELEASE; COEXISTENCE; NEUROPEPTIDES; PEPTIDES AB Nearly 40 putative neurotransmitters and other chemical messengers, mostly peptides, are present in the median eminence that constitutes the final common pathway for signals from the brain to the pituitary. The majority of them are produced in perikarya located in different nuclei of the hypothalamus; however, some of them arise from the brainstem. The neurons contacting capillaries of the median eminence (hypophysiotropic neurons) are intermixed with neurons containing the same transmitter (hypophysiotropic factor1), but projecting to other areas of the brain. Depending on their site of release, the hypophysiotropic factors may function as neurohormones acting on the pituitary or neurotransmitters affecting the activity of other neurons in the central nervous system. Based on retrograde tracing studies in combination with immunocytochemistry, the origin of many nerve terminals in the median eminence has been determined. RP MERCHENTHALER, I (reprint author), NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,FUNCT MORPHOL SECT,RES TRIANGLE PK,NC 27709, USA. NR 35 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD NOV-DEC PY 1991 VL 2 IS 6 BP 219 EP 226 DI 10.1016/1043-2760(91)90028-L PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GU462 UT WOS:A1991GU46200004 PM 18411186 ER PT J AU LOWY, DR ZHANG, KE DECLUE, JE WILLUMSEN, BM AF LOWY, DR ZHANG, KE DECLUE, JE WILLUMSEN, BM TI REGULATION OF P21RAS ACTIVITY SO TRENDS IN GENETICS LA English DT Review ID GTPASE-ACTIVATING PROTEIN; SACCHAROMYCES-CEREVISIAE; RAS PROTEINS; GENE-PRODUCT; CATALYTIC DOMAIN; MAMMALIAN GAP; IDENTIFICATION; CELLS; STIMULATION; YEAST AB The ras genes encode GTP/GDP-binding proteins that participate in mediating mitogenic signals from membrane tyrosine kinases to downstream targets. The activity of p21ras is determined by the concentration of GTP-p21ras, which is tightly regulated by a complex array of positive and negative control mechanisms. GAP and NF1 can negatively regulate p21ras activity by stimulating hydrolysis of GTP bound to p21ras. Other cellular factors can positively regulate p21ras by stimulating GDP/GTP exchange. C1 UNIV COPENHAGEN,INST MICROBIOL,DK-1353 COPENHAGEN,DENMARK. RP LOWY, DR (reprint author), NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892, USA. RI Willumsen, Berthe/H-1903-2012 OI Willumsen, Berthe/0000-0002-2277-6999 NR 54 TC 71 Z9 72 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD NOV-DEC PY 1991 VL 7 IS 11-12 BP 346 EP 351 DI 10.1016/0168-9525(91)90253-M PG 6 WC Genetics & Heredity SC Genetics & Heredity GA GN927 UT WOS:A1991GN92700002 PM 1820685 ER PT J AU WINSLOW, JT INSEL, TR AF WINSLOW, JT INSEL, TR TI THE INFANT RAT SEPARATION PARADIGM - A NOVEL TEST FOR NOVEL ANXIOLYTICS SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Editorial Material ID ULTRASONIC ISOLATION CALLS; PUP ISOLATION CALLS; RECEPTOR COMPLEX; ACID; VOCALIZATIONS; ANTAGONISTS; DIAZEPAM RP WINSLOW, JT (reprint author), NIMH,CTR ANIM,CLIN SCI LAB,POOLESVILLE,MD 20879, USA. NR 23 TC 87 Z9 88 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD NOV PY 1991 VL 12 IS 11 BP 402 EP 404 DI 10.1016/0165-6147(91)90616-Z PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GQ090 UT WOS:A1991GQ09000003 PM 1686685 ER PT J AU RELYVELD, E OATO, NH GUERIN, N COURSAGET, P HUET, M GUPTA, RK AF RELYVELD, E OATO, NH GUERIN, N COURSAGET, P HUET, M GUPTA, RK TI DETERMINATION OF CIRCULATING ANTIBODIES DIRECTED TO PERTUSSIS TOXIN AND OF AGGLUTINOGENS IN CHILDREN VACCINATED WITH EITHER THE WHOLE CELL OR COMPONENT PERTUSSIS-VACCINE IN FRANCE, JAPAN AND SENEGAL SO VACCINE LA English DT Article DE IMMUNIZATION OF CHILDREN; WHOLE CELL PERTUSSIS VACCINE; COMPONENT PERTUSSIS VACCINE; AGGLUTININS; ANTIBODIES TO PERTUSSIS TOXIN ID BORDETELLA-PERTUSSIS; FILAMENTOUS HEMAGGLUTININ; GLUTARALDEHYDE AB The antibody response to pertussis toxin (PT) and agglutinogens of children vaccinated in Japan, France and Senegal with either whole cell or component pertussis vaccine was determined at various times after immunization. Agglutinin titres were almost similar in sera of Japanese children vaccinated with either whole cell or component pertussis vaccine whereas anti-PT antibody levels were found to be higher after vaccination with whole cell vaccine than with component vaccine. The geometric mean (GM) agglutinin titres in sera of Japanese children amounted to 45.0 and 45.7, respectively, and neutralization GM titres to 71.6 and 22.6, respectively, following vaccination with the whole cell and component pertussis vaccines. Sera of French children receiving three doses of whole cell vaccine exhibited a GM agglutinin titre of 17.8, whereas only 16% of sera contained neutralizing antibodies against PT. Following the booster dose the GM agglutinin titre rose to 213.5 and 68% of the sera contained neutralizing antibodies to PT (GM titre 48.0). Sera of Senegalese children receiving three doses of whole cell vaccine exhibited a GM agglutinin titre of 18.7, whereas anti-PT neutralizing antibodies were hardly detected. Agglutinins and anti-PT antibody in sera of French and Senegalese children turned out to be lower than were found 25 years ago in sera of children immunized with the French whole cell pertussis vaccine. C1 INT CHILDRENS CTR,F-75016 PARIS,FRANCE. FAC MED & PHARM TOURS,INST VIROL TOURS,F-37000 TOURS,FRANCE. INST BOUISSON BERTRAND,F-34090 MONTPELLIER,FRANCE. NIH,BETHESDA,MD 20892. RP RELYVELD, E (reprint author), INST PASTEUR FDN,UNITE VACCINS BACTERIENS,F-92430 MARNES COQUETTE,FRANCE. NR 39 TC 13 Z9 14 U1 0 U2 3 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD NOV PY 1991 VL 9 IS 11 BP 843 EP 850 DI 10.1016/0264-410X(91)90224-T PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA GN417 UT WOS:A1991GN41700015 PM 1759508 ER PT J AU YOSHITOMI, K BOORMAN, GA AF YOSHITOMI, K BOORMAN, GA TI INTRAOCULAR AND ORBITAL MALIGNANT SCHWANNOMAS IN F344 RATS SO VETERINARY PATHOLOGY LA English DT Article DE EYE; NEURILEMOMA; ORBIT; RATS; SCHWANNOMA ID FIBRILLARY ACIDIC PROTEIN; NERVE SHEATH TUMORS; BENIGN; DIAGNOSIS; SPECTRUM AB Intraocular and orbital malignant Schwannomas in two F344 rats are presented. The two Schwannomas were identified among approximately 60,000 male and 60,000 female F344 rats. The intraocular malignant Schwannoma occurred in the iris, invading the corneal stroma through the destroyed Descemet membrane. The malignant orbital Schwannoma occurred in the left orbit, invading the contralateral orbit along the optic nerve. Histologically, the intraocular Schwannoma consisted predominantly of a perivascular fascicular pattern of plump spindle cells associated with marked cytoplasmic vacuolization. The orbital Schwannoma consisted of Antoni type A and B pattern, but Antoni B tissues predominated. Antoni A tissues consisted of closely packed, elongated spindle cells arranged in interlacing fascicles, while Antoni B tissues were highly cellular and consisted of anaplastic, small cells associated with marked cyst formation. Immunohistochemically, the intraocular Schwannoma had a positive immunoreactivity for S-100 protein, while the orbital Schwannoma had a negative immunoreactivity. Ultrastructurally, the cells of both intraocular and orbital Schwannomas had long, thin cell processes and pericytoplasmic basal laminae. Particularly, the plump spindle cells of the intraocular Schwannoma were most strikingly characterized by the well developed, extremely attenuated cell processes arranged in a lamellar or spiral pattern. These cell processes and cell bodies were associated with numerous desmosomes. Intracytoplasmic filamentous granules and bodies, consisting of intermediate filaments approximately 7 nm in width, were additional characteristics of the plump spindle cells. C1 NIEHS,NATL TOXICOL PROGRAM,CHEM CARCINOGENESIS BRANCH,RES TRIANGLE PK,NC 27709. RP YOSHITOMI, K (reprint author), EXPTL PATHOL LABS INC,POB 12766,RES TRIANGLE PK,NC 27709, USA. NR 23 TC 10 Z9 10 U1 0 U2 0 PU AMER COLL VET PATHOLOGIST PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 SN 0300-9858 J9 VET PATHOL JI Vet. Pathol. PD NOV PY 1991 VL 28 IS 6 BP 457 EP 466 PG 10 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA GR514 UT WOS:A1991GR51400001 PM 1771736 ER PT J AU LIU, JM GREEN, SW HAO, YS MCDONAGH, KT YOUNG, NS SHIMADA, T AF LIU, JM GREEN, SW HAO, YS MCDONAGH, KT YOUNG, NS SHIMADA, T TI UPSTREAM SEQUENCES WITHIN THE TERMINAL HAIRPIN POSITIVELY REGULATE THE P6 PROMOTER OF B19 PARVOVIRUS SO VIROLOGY LA English DT Article ID ADENO-ASSOCIATED VIRUS; DIHYDROFOLATE-REDUCTASE GENE; TRANSCRIPTION FACTOR; NONSTRUCTURAL PROTEIN; FIREFLY LUCIFERASE; MAMMALIAN-CELLS; MINUTE VIRUS; CDNA CLONES; EXPRESSION; INVITRO C1 NHLBI,CLIN HEMATOL BRANCH,BLDG 10,ROOM 7C 103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 38 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 0042-6822 J9 VIROLOGY JI Virology PD NOV PY 1991 VL 185 IS 1 BP 39 EP 47 DI 10.1016/0042-6822(91)90751-V PG 9 WC Virology SC Virology GA GJ980 UT WOS:A1991GJ98000006 PM 1926783 ER PT J AU DICKIE, P FELSER, J ECKHAUS, M BRYANT, J SILVER, J MARINOS, N NOTKINS, AL AF DICKIE, P FELSER, J ECKHAUS, M BRYANT, J SILVER, J MARINOS, N NOTKINS, AL TI HIV-ASSOCIATED NEPHROPATHY IN TRANSGENIC MICE EXPRESSING HIV-1 GENES SO VIROLOGY LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; RENAL-DISEASE; AIDS; GLOMERULOSCLEROSIS; RETROVIRUS; PROTEIN; CELLS; RECEPTOR; ANTIGEN; LESIONS C1 NIDR,ORAL MED LAB,BETHESDA,MD 20892. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,BETHESDA,MD 20892. NIDR,ANIM CARE UNIT,BETHESDA,MD 20892. OI Silver, Jonathan/0000-0001-9231-6368 NR 38 TC 189 Z9 190 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD NOV PY 1991 VL 185 IS 1 BP 109 EP 119 DI 10.1016/0042-6822(91)90759-5 PG 11 WC Virology SC Virology GA GJ980 UT WOS:A1991GJ98000014 PM 1926769 ER PT J AU JOHNSON, PR HAMM, TE GOLDSTEIN, S KITOV, S HIRSCH, VM AF JOHNSON, PR HAMM, TE GOLDSTEIN, S KITOV, S HIRSCH, VM TI THE GENETIC FATE OF MOLECULARLY CLONED SIMIAN IMMUNODEFICIENCY VIRUS IN EXPERIMENTALLY INFECTED MACAQUES SO VIROLOGY LA English DT Article ID AIDS VIRUSES; RETROVIRUS; SEQUENCE; MONKEYS; HIV; IDENTIFICATION; SUBSTITUTIONS; EXPRESSION; EVOLUTION; FREQUENCY C1 GEORGETOWN UNIV,DEPT MICROBIOL,DIV MOLEC VIROL & IMMUNOL,RETROVIRAL PATHOGENESIS SECT,ROCKVILLE,MD 20852. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. RI Johnson, Philip/A-6892-2009 FU NIAID NIH HHS [N01-AI-72623] NR 29 TC 119 Z9 119 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD NOV PY 1991 VL 185 IS 1 BP 217 EP 228 DI 10.1016/0042-6822(91)90769-8 PG 12 WC Virology SC Virology GA GJ980 UT WOS:A1991GJ98000024 PM 1926774 ER PT J AU DEVICO, A MONTELARO, RC GALLO, RC SARNGADHARAN, MG AF DEVICO, A MONTELARO, RC GALLO, RC SARNGADHARAN, MG TI PURIFICATION AND PARTIAL CHARACTERIZATION OF EQUINE INFECTIOUS-ANEMIA VIRUS REVERSE-TRANSCRIPTASE SO VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; COMPLETE NUCLEOTIDE-SEQUENCE; IMMUNE-DEFICIENCY SYNDROME; ANTIGENIC VARIATION; AIDS VIRUS; PERSISTENT INFECTION; ESCHERICHIA-COLI; HTLV-III; RETROVIRUS; LENTIVIRUS C1 ADV BIOSCI LABS INC,DEPT CELL BIOL,KENSINGTON,MD 20895. UNIV PITTSBURGH,DEPT MOLEC GENET,PITTSBURGH,PA 15260. UNIV PITTSBURGH,DEPT BIOCHEM,PITTSBURGH,PA 15260. NCI,TUMOR CELL BIOL LAB,BALTIMORE,MD 21211. FU NCI NIH HHS [R01 CA49296, N01-CP-73723]; NIAID NIH HHS [R01 AI25850] NR 38 TC 21 Z9 21 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD NOV PY 1991 VL 185 IS 1 BP 387 EP 394 DI 10.1016/0042-6822(91)90786-B PG 8 WC Virology SC Virology GA GJ980 UT WOS:A1991GJ98000041 PM 1718086 ER PT J AU BRAY, M LAI, CJ AF BRAY, M LAI, CJ TI DENGUE VIRUS PREMEMBRANE AND MEMBRANE-PROTEINS ELICIT A PROTECTIVE IMMUNE-RESPONSE SO VIROLOGY LA English DT Note ID RECOMBINANT VACCINIA VIRUS; STRUCTURAL PROTEINS; NONSTRUCTURAL PROTEIN-NS1; SEQUENCE; EXPRESSION; MICE C1 NIAID,INFECT DIS LAB,MOLEC VIRAL BIOL SECT,BETHESDA,MD 20892. NR 14 TC 66 Z9 73 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD NOV PY 1991 VL 185 IS 1 BP 505 EP 508 DI 10.1016/0042-6822(91)90809-P PG 4 WC Virology SC Virology GA GJ980 UT WOS:A1991GJ98000064 PM 1926792 ER PT J AU MILLER, DL AF MILLER, DL TI PREOPERATIVE LOCALIZATION AND INTERVENTIONAL TREATMENT OF PARATHYROID TUMORS - WHEN AND HOW SO WORLD JOURNAL OF SURGERY LA English DT Article ID HIGH-RESOLUTION ULTRASOUND; PRIMARY HYPERPARATHYROIDISM; RECURRENT HYPERPARATHYROIDISM; SUBTRACTION SCINTIGRAPHY; ANGIOGRAPHIC ABLATION; UNDERGONE SURGERY; ASPIRATION BIOPSY; CONTRAST AGENT; NEEDLE-BIOPSY; ADENOMAS AB A variety of diagnostic tests are currently used for parathyroid localization. In patients who have not had previous surgery, none of these are as sensitive or specific for the localization of abnormal parathyroid glands as an experienced surgeon. In these patients, no pre-operative localization procedures are normally needed. Patients who have had previous thyroid or parathyroid surgery require pre-operative localization. Noninvasive imaging procedures (ultrasound, scintigraphy, computed tomography, magnetic resonance imaging) should be performed until an abnormal gland is identified in the same location on at least 2 examinations. The order in which these studies are performed is not important. In the 50% to 70% of patients in whom noninvasive studies are inconclusive, suspicious lesions may be aspirated or biopsied with imaging guidance. If this cannot be done or is nondiagnostic, angiography and, if necessary, parathyroid venous sampling should be done. Intra-operative ultrasound examination of the neck is helpful during re-operations. In selected patients, parathyroid tumors may be ablated by injection of contrast material through an angiographic catheter into the artery supplying the gland, or by percutaneous injection of alcohol into the gland itself. Angiographic ablation is best used for mediastinal glands supplied by the internal thoracic artery or by a descending branch of the inferior thyroid artery. Percutaneous alcohol injection may injure the recurrent laryngeal nerve permanently and should be limited to the rare patient with a neck lesion who has a prohibitive surgical risk. Neither technique is as effective as surgery. C1 GEORGETOWN UNIV,MED CTR,DEPT RADIOL,WASHINGTON,DC 20007. RP MILLER, DL (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BLDG 10,BETHESDA,MD 20892, USA. NR 93 TC 94 Z9 94 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD NOV-DEC PY 1991 VL 15 IS 6 BP 706 EP 715 PG 10 WC Surgery SC Surgery GA GQ018 UT WOS:A1991GQ01800007 PM 1767536 ER PT J AU CARTY, SE NORTON, JA AF CARTY, SE NORTON, JA TI MANAGEMENT OF PATIENTS WITH PERSISTENT OR RECURRENT PRIMARY HYPERPARATHYROIDISM SO WORLD JOURNAL OF SURGERY LA English DT Article ID REOPERATIVE PARATHYROID SURGERY; HYPER-PARATHYROIDISM; UNDERGONE SURGERY; LOCALIZATION; ULTRASOUND; CARCINOMA; ADENOMAS AB The surgical management of patients with persistent or recurrent primary hyperparathyroidism is reviewed. The several factors allowing the surgeon to formulate a correct working diagnosis and to successfully remove all abnormal parathyroid tissue are individually discussed and recent results of re-operative parathyroid surgery are presented. In particular, direct surgical exploration based on aggressive pre-operative localization studies, the use of intra-operative ultrasound to facilitate intra-operative dissection, cryopreservation of excised parathyroid tissue with potential for delayed autograft to avoid permanent hypoparathyroidism, and the use of intra-operative monitoring of urinary cyclic adenosine monophosphate levels in patients with parathyroid hyperplasia in whom the surgeon is uncertain whether all abnormal parathyroid tissue has been removed, each contribute to a high rate of successful management (> 95%) for patients with the difficult problem of persistent or recurrent primary hyperparathyroidism. C1 NCI,SURG BRANCH,SURG METAB SECT,BLDG 10,ROOM 2B07,BETHESDA,MD 20892. NR 31 TC 55 Z9 55 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD NOV-DEC PY 1991 VL 15 IS 6 BP 716 EP 723 PG 8 WC Surgery SC Surgery GA GQ018 UT WOS:A1991GQ01800008 PM 1767537 ER PT J AU HIGGINS, DR STRATHERN, JN AF HIGGINS, DR STRATHERN, JN TI ELECTROPORATION-STIMULATED RECOMBINATION IN YEAST SO YEAST LA English DT Article DE YEAST RECOMBINATION; RAD52-DEPENDENT RECOMBINATION; ELECTROPORATION; DNA DAMAGE; INDUCED RECOMBINATION ID INTACT YEAST; SACCHAROMYCES-CEREVISIAE; HIGH-FREQUENCY; TRANSFORMATION; CELLS; DNA; GENES AB Saccharomyces cerevisiae cells treated by high voltage and made transformation-competent (electroporation) are also made hyper-recombinational as determined by an assay that measures interchromosomal mitotic recombination between chromosome III homologs, each containing mutant heteroallelic copies of the trp1 and his3 genes. There is a 10-fold stimulation of Trp+ and 21-fold stimulation of His+ prototrophs. Although this stimulation coincides with conditions for maximal transformation competence it is independent of the presence of transforming plasmid DNA. Electroporation does not increase the reversion frequency of these mutations, nor is there a stimulation in Ty transposition. Among the electroporation-stimulated Trp+ and His+ recombinants there is no dramatic difference in the pattern of events: that is to say that, while there is an increase in the number of recombinants, the distribution of gene conversion and cross-over events among the stimulated recombinants is not significantly altered compared to spontaneously arising Trp+ and His+ recombinants. This electroporation-stimulated recombination is abolished in an isogenic rad52 mutant strain consistent with the increase in Trp+ and His+ prototrophs being the result of a stimulation of a RAD52-dependent recombination pathway. C1 NCI,FREDERICK CANC RES & DEV CTR,EUKARYOT GENE EXPRESS LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 19 TC 16 Z9 17 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0749-503X J9 YEAST JI Yeast PD NOV PY 1991 VL 7 IS 8 BP 823 EP 831 DI 10.1002/yea.320070807 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA GT958 UT WOS:A1991GT95800006 PM 1789003 ER PT J AU JOHNSON, GR SAEKI, T AUERSPERG, N GORDON, AW SHOYAB, M SALOMON, DS STROMBERG, K AF JOHNSON, GR SAEKI, T AUERSPERG, N GORDON, AW SHOYAB, M SALOMON, DS STROMBERG, K TI RESPONSE TO AND EXPRESSION OF AMPHIREGULIN BY OVARIAN-CARCINOMA AND NORMAL OVARIAN SURFACE EPITHELIAL-CELLS - NUCLEAR-LOCALIZATION OF ENDOGENOUS AMPHIREGULIN SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID GROWTH; TRANSLOCATION; ANTIBODY; CULTURE; LINE C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. UNIV BRITISH COLUMBIA,DEPT ANAT,VANCOUVER V6T 1W5,BC,CANADA. ONCOGEN,BRISTOL MYERS SQUIBB PHARMACEUT RES INST,SEATTLE,WA 98121. RP JOHNSON, GR (reprint author), US FDA,DIV CYTOKINE BIOL,CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 20 TC 88 Z9 88 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 OCT 31 PY 1991 VL 180 IS 2 BP 481 EP 488 DI 10.1016/S0006-291X(05)81090-3 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GM638 UT WOS:A1991GM63800004 PM 1953719 ER PT J AU CHAUDHARY, VK FITZGERALD, DJ PASTAN, I AF CHAUDHARY, VK FITZGERALD, DJ PASTAN, I TI A PROPER AMINO TERMINUS OF DIPHTHERIA-TOXIN IS IMPORTANT FOR CYTOTOXICITY SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID RECEPTOR-BINDING DOMAIN; PSEUDOMONAS EXOTOXIN; ESCHERICHIA-COLI; MUTANT PROTEINS; FUSION PROTEIN; TARGET-CELLS; FRAGMENT-A; CYTOSOL; INTERLEUKIN-2; IMMUNOTOXIN C1 NCI,DIV CANC BIOL DIAGNOSIS & CTR,MOLEC BIOL LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 25 TC 32 Z9 33 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 OCT 31 PY 1991 VL 180 IS 2 BP 545 EP 551 DI 10.1016/S0006-291X(05)81099-X PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GM638 UT WOS:A1991GM63800013 PM 1953725 ER PT J AU ZHEN, WN JAYARAM, HN MARQUEZ, VE GOLDSTEIN, BM COONEY, DA WEBER, G AF ZHEN, WN JAYARAM, HN MARQUEZ, VE GOLDSTEIN, BM COONEY, DA WEBER, G TI CYTOTOXICITY OF TIAZOFURIN AND ITS ARABINOSE AND XYLOSE ANALOGS IN K562 CELLS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID 2-BETA-D-RIBOFURANOSYLTHIAZOLE-4-CARBOXAMIDE NSC 286193; ANTI-TUMOR AGENT; DEHYDROGENASE-ACTIVITY; THIAZOLE NUCLEOSIDE; MECHANISM; METABOLISM; LEUKEMIA; NAD C1 INDIANA UNIV,SCH MED,EXPTL ONCOL LAB,INDIANAPOLIS,IN 46202. NCI,MED CHEM LAB,BETHESDA,MD 20892. UNIV ROCHESTER,MED CTR,DEPT BIOPHYS,ROCHESTER,NY 14642. FU NCI NIH HHS [CA-42510, CA-51770] NR 17 TC 3 Z9 3 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 OCT 31 PY 1991 VL 180 IS 2 BP 933 EP 938 DI 10.1016/S0006-291X(05)81155-6 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GM638 UT WOS:A1991GM63800069 PM 1683233 ER PT J AU LI, ZH BURKE, TR BOLEN, JB AF LI, ZH BURKE, TR BOLEN, JB TI ANALYSIS OF STYRYL-BASED INHIBITORS OF THE LYMPHOCYTE TYROSINE PROTEIN KINASE-P56LCK SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID KINASE P56LCK; RECEPTOR; PHOSPHORYLATION; ACTIVATION; CD4; ASSOCIATION; ANTIGEN C1 NCI,MED CHEM LAB,BETHESDA,MD 20892. RP LI, ZH (reprint author), BRISTOL MYERS SQUIBB PHARMACEUT RES INST,DEPT MOLEC BIOL,PRINCETON,NJ 08543, USA. RI Burke, Terrence/N-2601-2014 NR 15 TC 16 Z9 16 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 OCT 31 PY 1991 VL 180 IS 2 BP 1048 EP 1056 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GM638 UT WOS:A1991GM63800086 PM 1659394 ER PT J AU BURROUGHS, JA CHRAMBACH, A AF BURROUGHS, JA CHRAMBACH, A TI SIZE SEPARATION OF POLYSTYRENE SULFATE PARTICLES (189 TO 1085 NM RADIUS) IN SOLUTIONS OF METHYL-HYDROXYPROPYL-CELLULOSE OF DIFFERENT CHAIN LENGTHS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID GEL-ELECTROPHORESIS RP BURROUGHS, JA (reprint author), NICHHD,THEORET & PHYS BIOL LAB,MACROMOLEC ANAL SECT,BETHESDA,MD 20892, USA. NR 9 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 31 PY 1991 VL 180 IS 2 BP 1070 EP 1074 DI 10.1016/S0006-291X(05)81175-1 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GM638 UT WOS:A1991GM63800089 PM 1953711 ER PT J AU MAEKAWA, M SUDO, K LI, SSL KANNO, T AF MAEKAWA, M SUDO, K LI, SSL KANNO, T TI ANALYSIS OF GENETIC MUTATIONS IN HUMAN LACTATE DEHYDROGENASE-A(M) DEFICIENCY USING DNA CONFORMATION POLYMORPHISM IN COMBINATION WITH POLYACRYLAMIDE GRADIENT GEL AND SILVER STAINING SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID M-SUBUNIT; AMPLIFICATION; POLYMERASE C1 JIKEI UNIV, DAISAN HOSP, SCH MED, DEPT LAB MED, KOMAE 201, JAPAN. NIEHS, GENET LAB, RES TRIANGLE PK, NC 27709 USA. RP MAEKAWA, M (reprint author), HAMAMATSU UNIV SCH MED, DEPT LAB MED, HANDA CHO 3600, HAMAMATSU, SHIZUOKA 431-31, JAPAN. NR 19 TC 23 Z9 24 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 31 PY 1991 VL 180 IS 2 BP 1083 EP 1090 DI 10.1016/S0006-291X(05)81177-5 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GM638 UT WOS:A1991GM63800091 PM 1953713 ER PT J AU KOSUGI, S BAN, T AKAMIZU, T KOHN, LD AF KOSUGI, S BAN, T AKAMIZU, T KOHN, LD TI FURTHER CHARACTERIZATION OF A HIGH-AFFINITY THYROTROPIN BINDING-SITE ON THE RAT THYROTROPIN RECEPTOR WHICH IS AN EPITOPE FOR BLOCKING ANTIBODIES FROM IDIOPATHIC MYXEDEMA PATIENTS BUT NOT THYROID STIMULATING ANTIBODIES FROM GRAVES PATIENTS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; TSH RECEPTOR; CDNA; AUTOANTIBODIES RP KOSUGI, S (reprint author), NIDDKD,BIOCHEM & METAB LAB,CELL REGULAT SECT,BETHESDA,MD 20892, USA. NR 17 TC 58 Z9 59 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 31 PY 1991 VL 180 IS 2 BP 1118 EP 1124 DI 10.1016/S0006-291X(05)81182-9 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GM638 UT WOS:A1991GM63800096 PM 1719963 ER PT J AU BAKER, TA AF BAKER, TA TI AND THEN THERE WERE 2 SO NATURE LA English DT Editorial Material ID COLE1 RP BAKER, TA (reprint author), NIDDKD,BETHESDA,MD 20892, USA. NR 6 TC 5 Z9 5 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 OCT 31 PY 1991 VL 353 IS 6347 BP 794 EP 795 DI 10.1038/353794a0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GM732 UT WOS:A1991GM73200032 PM 1944553 ER PT J AU DOHURA, K KITAMOTO, T SAKAKI, Y TATEISHI, J AF DOHURA, K KITAMOTO, T SAKAKI, Y TATEISHI, J TI CJD DISCREPANCY SO NATURE LA English DT Letter C1 KYUSHU UNIV,INST NEUROL,DEPT NEUROPATHOL,FUKUOKA 812,JAPAN. KYUSHU UNIV,GENET INFORMAT LAB,FUKUOKA 812,JAPAN. RP DOHURA, K (reprint author), NIAID,ROCKY MT LABS,LPVD,HAMILTON,MT 59840, USA. NR 0 TC 91 Z9 92 U1 0 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD OCT 31 PY 1991 VL 353 IS 6347 BP 801 EP 802 DI 10.1038/353801b0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GM732 UT WOS:A1991GM73200040 PM 1682813 ER PT J AU WESTWOOD, JT CLOS, J WU, C AF WESTWOOD, JT CLOS, J WU, C TI STRESS-INDUCED OLIGOMERIZATION AND CHROMOSOMAL RELOCALIZATION OF HEAT-SHOCK FACTOR SO NATURE LA English DT Article ID DNA-BINDING PROPERTIES; DROSOPHILA-MELANOGASTER; TRANSCRIPTION FACTOR; RNA-POLYMERASE; PROTEINS; INVITRO; GENE; ACTIVATION; LOCALIZATION; UPSTREAM AB The induction of heat-shock transcription factor (HSF) binding to DNA is accomplished by a heat-induced oligomerization. The transition to the induced state is accompanied by a chromosomal redistribution of HSF to the heat-shock puff sites. Over 150 additional chromosomal sites also accumulate HSF, including developmental loci that are repressed during heat shock. These findings suggest an unforeseen role for HSF as a repressor of normal gene activity during heat stress. RP WESTWOOD, JT (reprint author), NCI,BIOCHEM LAB,BG 37,RM 4C-09,BETHESDA,MD 20892, USA. NR 56 TC 292 Z9 298 U1 0 U2 18 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD OCT 31 PY 1991 VL 353 IS 6347 BP 822 EP 823 DI 10.1038/353822a0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GM732 UT WOS:A1991GM73200051 PM 1944557 ER PT J AU PAOLINI, R JOUVIN, MH KINET, JP AF PAOLINI, R JOUVIN, MH KINET, JP TI PHOSPHORYLATION AND DEPHOSPHORYLATION OF THE HIGH-AFFINITY RECEPTOR FOR IMMUNOGLOBULIN-E IMMEDIATELY AFTER RECEPTOR ENGAGEMENT AND DISENGAGEMENT SO NATURE LA English DT Article ID CELL ANTIGEN RECEPTOR; NATURAL-KILLER-CELLS; FC-GAMMA RECEPTOR; IGE RECEPTOR; ZETA-CHAIN; MOLECULAR-CLONING; CD16; EXPRESSION; SUBUNIT; RIII AB TRIGGERING of mast cells and basophils by immunoglobulin E (IgE) and antigen induces various biochemical signals, including tyrosine kinase activation 1,2, which lead to cell degranulation and the release of mediators of the allergic reaction. The high-affinity receptor for IgE (Fc-epsilon-RI) responsible for initiating these events is a complex structure composed of an IgE-binding alpha-chain, a beta-chain and a homodimer of gamma-chains 3. It has been assumed that beta and gamma, which have extensive cytoplasmic domains, play an important but undefined role in coupling Fc-epsilon-RI to signal transduction mechanisms. Here we show that Fc-epsilon-RI engagement induces immediate in vivo phosphorylation on beta (tyrosine and serine) and gamma (tyrosine and threonine) by at least two different non-receptor kinases. We take advantage of unique features of this receptor system to demonstrate that the phosphorylation signal is restricted to activated receptors and is immediately reversible upon receptor disengagement by undefined phosphatases. Rapid phosphorylation and dephosphorylation may be a general mechanism to couple and uncouple activated receptors to other effector molecules. This could be particularly relevant to other multimeric receptors containing Fc-epsilon-RI gamma-chains or the related-zeta and eta-chains such as the T-cell antigen receptor (TCR) 4-6 and the low-affinity receptor for immunoglobulin G (Fc-gamma-RIII, CD16) (refs 7-11). RP PAOLINI, R (reprint author), NIAID,MOLEC ALLERGY & IMMUNOL SECT,TWINBROOK II BLDG,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. NR 28 TC 274 Z9 274 U1 0 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD OCT 31 PY 1991 VL 353 IS 6347 BP 855 EP 858 DI 10.1038/353855a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GM732 UT WOS:A1991GM73200063 PM 1834946 ER PT J AU LENARDO, MJ AF LENARDO, MJ TI INTERLEUKIN-2 PROGRAMS MOUSE ALPHA-BETA-LYMPHOCYTES-T FOR APOPTOSIS SO NATURE LA English DT Article ID STAPHYLOCOCCAL ENTEROTOXIN-B; CELL ANTIGEN RECEPTOR; STIMULATORY FACTOR-I; MONOCLONAL-ANTIBODY; PROLIFERATION; INVIVO; ACTIVATION; CLONES; UNRESPONSIVENESS; THYMOCYTES AB ANTIGEN receptor stimulation of mature alpha-beta-T lymphocytes can lead either to proliferation or death 1-4. Programmed cell death, termed apoptosis, leads to the clonal deletion of both thymocytes and mature T cells that establishes tolerance 5-9. How a mature T cell selects between proliferation and death is not understood. Here I show that interleukin-2 (IL-2) is a critical determinant of the choice between these two fates. Both CD4+ and CD8+ T cells previously exposed to IL-2 undergo apoptosis after antigen-receptor stimulation. Antibody blockade of IL-2 but not IL-4 reverses the marked reduction of lymph node V-beta-38+ T cells caused in mice by the bacterial superantigen Staphylococcus aureus enterotoxin B. IL-2 may thus participate in a feedback regulatory mechanism by predisposing mature T lymphocytes to apoptosis. RP LENARDO, MJ (reprint author), NIAID,IMMUNOL LAB,BLDG 10,RM 11N311,BETHESDA,MD 20892, USA. NR 29 TC 897 Z9 912 U1 1 U2 7 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD OCT 31 PY 1991 VL 353 IS 6347 BP 858 EP 861 DI 10.1038/353858a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GM732 UT WOS:A1991GM73200064 PM 1944559 ER PT J AU WINGARD, JR MERZ, WG RINALDI, MG JOHNSON, TR KARP, JE SARAL, R AF WINGARD, JR MERZ, WG RINALDI, MG JOHNSON, TR KARP, JE SARAL, R TI INCREASE IN CANDIDA-KRUSEI INFECTION AMONG PATIENTS WITH BONE-MARROW TRANSPLANTATION AND NEUTROPENIA TREATED PROPHYLACTICALLY WITH FLUCONAZOLE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TORULOPSIS-GLABRATA; FUNGEMIA; FREQUENCY; CANCER; FEVER; COLONIZATION; THERAPY AB Background. In early 1990 fluconazole was introduced as a prophylactic antifungal agent after bone marrow transplantation. During the same year Candida krusei emerged as the chief candida pathogen among patients with bone marrow transplants. Methods. To determine whether there was a correlation between the introduction of fluconazole and the increased incidence of C. krusei, we conducted a retrospective study based on the medical, mycologic, and autopsy records of all adult inpatients who had undergone bone marrow transplantation (n = 296) or who had leukemia (n = 167) at the study center during 1989 and 1990. Results. The 84 patients who received antifungal prophylaxis with fluconazole had a sevenfold greater frequency of C. krusei infection than the 335 patients who did not receive fluconazole (8.3 percent vs. 1.2 percent, P = 0.002), despite having a lower frequency of disseminated C. albicans and C. tropicalis infections (0 vs. 6.0 percent, P = 0.02). Ten of the 11 C. krusei infections were controlled by a combination of amphotericin B and flucytosine. Colonization by C. krusei was found in 40.5 percent of the patients who received fluconazole but in only 16.7 percent of those who did not receive it (P < 0.0001). Colonization was independently associated with the prophylactic use of both fluconazole (odds ratio, 3.50; P < 0.001) and norfloxacin (odds ratio, 2.53; P = 0.04). C. krusei was not susceptible to fluconazole in vitro. Conclusions. In patients at high risk for disseminated candida infections, suppression of bacterial flora and the more common candida pathogens may permit some less pathogenic, but natively resistant candida species, such as C. krusei, to emerge as systemic pathogens. C1 JOHNS HOPKINS MED INST,DEPT LAB MED,BALTIMORE,MD 21205. JOHNS HOPKINS MED INST,CTR ONCOL,BALTIMORE,MD 21205. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. NCI,OFF DIRECTOR,BETHESDA,MD 20892. RP WINGARD, JR (reprint author), EMORY UNIV,SCH MED,DEPT MED,DIV HEMATOL ONCOL,BONE MARROW TRANSPLANT PROGRAM,ATLANTA,GA 30322, USA. FU NCI NIH HHS [CA06973, CA15396] NR 21 TC 773 Z9 788 U1 1 U2 12 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 OCT 31 PY 1991 VL 325 IS 18 BP 1274 EP 1277 DI 10.1056/NEJM199110313251803 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA GM041 UT WOS:A1991GM04100003 PM 1669837 ER PT J AU JAROSINSKI, PF HIRSCHFELD, S AF JAROSINSKI, PF HIRSCHFELD, S TI PRECIPITATION OF ONDANSETRON IN ALKALINE-SOLUTIONS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID GR-38032F; SEROTONIN C1 NCI,BETHESDA,MD 20892. RP JAROSINSKI, PF (reprint author), NIH,BETHESDA,MD 20892, USA. RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 2 TC 4 Z9 4 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 31 PY 1991 VL 325 IS 18 BP 1315 EP 1316 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA GM041 UT WOS:A1991GM04100021 PM 1656257 ER PT J AU SPENCER, RGS HALVERSON, KJ AUGER, M MCDERMOTT, AE GRIFFIN, RG LANSBURY, PT AF SPENCER, RGS HALVERSON, KJ AUGER, M MCDERMOTT, AE GRIFFIN, RG LANSBURY, PT TI AN UNUSUAL PEPTIDE CONFORMATION MAY PRECIPITATE AMYLOID FORMATION IN ALZHEIMERS-DISEASE - APPLICATION OF SOLID-STATE NMR TO THE DETERMINATION OF PROTEIN SECONDARY STRUCTURE SO BIOCHEMISTRY LA English DT Note ID MAGIC-ANGLE; ROTATIONAL RESONANCE; BETA-FIBRILLOSES; SPIN DIFFUSION; DEPOSITS; SYSTEMS; ISOMER; SHEETS AB The formation of insoluble proteinaceous deposits is characteristic of many diseases which are collectively known as amyloidosis. There is very little molecular-level structural information available regarding the amyloid deposits due to the fact that the constituent proteins are insoluble and noncrystalline. Therefore, traditional protein structure determination methods such as solution NMR and X-ray crystallography are not applicable. We report herein the application of the solid-state NMR technique rotational resonance (R2) to the accurate measurement of carbon-to-carbon distances in the amyloid formed from a synthetic fragment (H2N-LeuMetValGlyGlyValValIleAla-CO2H) of the amyloid-forming protein of Alzheimer's disease (AD). This sequence has been implicated in the initiation of amyloid formation. Two distances measured by R2 indicate that an unusual structure, probably involving a cis amide bond, is present in the aggregated peptide amyloid. This structure is incompatible with the accepted models of fibril structure. A relationship between this structure and the stability of the amyloid is proposed. C1 MIT,DEPT CHEM,CAMBRIDGE,MA 02139. MIT,FRANCIS BITTER NATL MAGNET LAB,CAMBRIDGE,MA 02139. NIA,GERONTOL RES CTR,CELLULAR & MOLEC BIOL LAB,BALTIMORE,MD 21224. OI McDermott, Ann/0000-0002-9249-1649 FU NCRR NIH HHS [RR00995]; NIA NIH HHS [AG08470]; NIGMS NIH HHS [GM23403] NR 48 TC 94 Z9 94 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 29 PY 1991 VL 30 IS 43 BP 10382 EP 10387 DI 10.1021/bi00107a004 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GM613 UT WOS:A1991GM61300004 PM 1931962 ER PT J AU DURCAN, MJ MORGAN, PF AF DURCAN, MJ MORGAN, PF TI HYPOTHERMIC EFFECTS OF ALKYLXANTHINES - EVIDENCE FOR A CALCIUM-INDEPENDENT PHOSPHODIESTERASE ACTION SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE CAFFEINE; THEOPHYLLINE; PHOSPHODIESTERASE INHIBITION; ADENOSINE RECEPTORS; BODY TEMPERATURE; (MOUSE) ID REDUCED ADIPSIN EXPRESSION; DRUG MIXTURE EPHEDRINE; CYCLIC-AMP; RECTAL TEMPERATURE; ADENOSINE-ANALOGS; MURINE OBESITY; CAFFEINE; NUCLEOTIDES; FORSKOLIN; ROLIPRAM AB Caffeine induces a dose-dependent decrease in core body temperature in mice and the hypothermia induced by a 100 mg/kg dose of caffeine was seen to persist for greater than 160 min. Other alkylxanthines including theophylline, enprophylline, isobutylmethylxanthine and 1,3-dipropyl-7-methylxanthine also showed dose-dependent reductions in body temperature. The dose of these drugs required to reduce body temperature by 2-degrees-C was calculated and correlated with the affinities for the compounds at adenosine A1 and A2 receptors and their activities in inhibiting calcium dependent and independent phosphodiesterases. Significant relationships were found between the 2-degrees-C hypothermic dose (HD2) and soluble and membrane calcium-independent phosphodiesterase inhibiting activity (r2s = 0.950 and 0.940, respectively). No significant relationship was seen between HD2 and soluble calcium-dependent phosphodiesterase inhibiting activity or with A2 adenosine receptor affinity. The relationship between HD2 and A1 adenosine receptor affinity (r2 = 0.739) did however almost reach statistical significance. These results would suggest that phosphodiesterase inhibition, instead of or in addition to adenosine receptor blockade, may play an important role in the effects of alkylxanthines on body temperature. RP DURCAN, MJ (reprint author), NIAAA,CLIN STUDIES LAB,DICBR,BLDG 10,ROOM 3C102,BETHESDA,MD 20892, USA. NR 29 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD OCT 29 PY 1991 VL 204 IS 1 BP 15 EP 20 DI 10.1016/0014-2999(91)90829-F PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GN897 UT WOS:A1991GN89700003 PM 1804662 ER PT J AU LAKE, JR HAMMOND, MV SHADDOX, RC HUNSICKER, LM YANG, HYT MALIN, DH AF LAKE, JR HAMMOND, MV SHADDOX, RC HUNSICKER, LM YANG, HYT MALIN, DH TI IGG FROM NEUROPEPTIDE FF ANTISERUM REVERSES MORPHINE-TOLERANCE IN THE RAT SO NEUROSCIENCE LETTERS LA English DT Article DE OPIATE; OPIATE TOLERANCE; FMRFAMIDE; FMRFAMIDE-RELATED PEPTIDE; F8FAMIDE; ANTIOPIATE PEPTIDE; ANALGESIA; NEUROPEPTIDE FF ID SPINAL-CORD; PEPTIDES; BRAIN; ABSTINENCE AB Previous studies suggest that neuropeptide FF (NPFF) plays a role in opiate dependence and subsequent abstinence syndrome. The present study assessed the role of NPFF in opiate tolerance. Third ventricular injection of IgG from NPFF antiserum restored the analgesic response to i.c.v. morphine in morphine-tolerant rats (radiant heat tail flick test). IgG from control serum failed to produce this effect. In opiate-naive rats, however, the same treatment with IgG from NPFF antiserum did not affect the analgesic response to i.c.v. morphine. Thus, immunoneutralization of NPFF appears to selectively restore morphine sensitivity in opiate-tolerant animals. These results support the hypothesis that endogenous NPFF contributes to opiate tolerance. C1 UNIV HOUSTON CLEAR LAKE, BOX 337, HOUSTON, TX 77058 USA. ST ELIZABETH HOSP, NIMH, CTR NEUROSCI, BIOCHEM GENET LAB, WASHINGTON, DC 20032 USA. NR 18 TC 104 Z9 105 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD OCT 28 PY 1991 VL 132 IS 1 BP 29 EP 32 DI 10.1016/0304-3940(91)90425-S PG 4 WC Neurosciences SC Neurosciences & Neurology GA GN665 UT WOS:A1991GN66500009 PM 1787914 ER PT J AU NEEQUAYE, JE BYRNE, J LEVINE, PH AF NEEQUAYE, JE BYRNE, J LEVINE, PH TI MENARCHE AND REPRODUCTION AFTER TREATMENT FOR AFRICAN BURKITTS-LYMPHOMA SO BRITISH MEDICAL JOURNAL LA English DT Article ID GONADAL DAMAGE C1 NCI,EPIDEMIOL & BIOSTAT PROGRAM,EPN 400,BETHESDA,MD 20892. UNIV GHANA,SCH MED,DEPT CHILD HLTH,BURKITTS TUMOR PROJECT,ACCRA,GHANA. FU NCI NIH HHS [N01-CP-51009] NR 5 TC 2 Z9 2 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD OCT 26 PY 1991 VL 303 IS 6809 BP 1033 EP 1033 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GM478 UT WOS:A1991GM47800022 PM 1954456 ER PT J AU GRUNDY, P TELZEROW, P PATERSON, MC HABER, D BERMAN, B LI, F GARBER, J AF GRUNDY, P TELZEROW, P PATERSON, MC HABER, D BERMAN, B LI, F GARBER, J TI CHROMOSOME-11 UNIPARENTAL ISODISOMY PREDISPOSING TO EMBRYONAL NEOPLASMS SO LANCET LA English DT Letter ID ADRENOCORTICAL CARCINOMA; WILMS TUMOR; 11P15.5 C1 CROSS CANC INST,DEPT PEDIAT,EDMONTON T6G 1Z2,ALBERTA,CANADA. UNIV ALBERTA,FAC MED,EDMONTON T6G 2E1,ALBERTA,CANADA. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02114. CASE WESTERN RESERVE UNIV,SCH MED,DEPT PEDIAT,CLEVELAND,OH 44106. NCI,CLIN EPIDEMIOL BRANCH,CLIN STUDIES SECT,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. RP GRUNDY, P (reprint author), CROSS CANC INST,DEPT MED,EDMONTON T6G 1Z2,ALBERTA,CANADA. NR 10 TC 71 Z9 72 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 OCT 26 PY 1991 VL 338 IS 8774 BP 1079 EP 1080 DI 10.1016/0140-6736(91)91937-P PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA GM253 UT WOS:A1991GM25300041 PM 1681381 ER PT J AU SCRIMGEOUR, EM BROWN, P AF SCRIMGEOUR, EM BROWN, P TI BSE AND POTENTIAL RISKS TO SLAUGHTERMEN SO VETERINARY RECORD LA English DT Letter C1 NIH,CENT NERVOUS SYST DIS LAB,BETHESDA,MD 20892. RP SCRIMGEOUR, EM (reprint author), LANARKSHIRE HLTH BOARD,14 BECKFORD ST,HAMILTON,SCOTLAND. NR 5 TC 2 Z9 2 U1 0 U2 0 PU BRITISH VETERINARY ASSOC PI LONDON PA 7 MANSFIELD ST, LONDON, ENGLAND W1M 0AT SN 0042-4900 J9 VET REC JI Vet. Rec. PD OCT 26 PY 1991 VL 129 IS 17 BP 390 EP 391 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA GN418 UT WOS:A1991GN41800013 PM 1746122 ER PT J AU HAGGER, C BACHEVALIER, J AF HAGGER, C BACHEVALIER, J TI VISUAL HABIT FORMATION IN 3-MONTH-OLD MONKEYS (MACACA-MULATTA) - REVERSAL OF SEX DIFFERENCE FOLLOWING NEONATAL MANIPULATIONS OF ANDROGENS SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE SEX DIFFERENCE; HABIT FORMATION; ANDROGEN; INFANT MONKEY ID GONADAL-HORMONES; RHESUS-MONKEYS; FEMALE RATS; TESTOSTERONE; BRAIN; PRIMATE AB The ability to perform on a concurrent visual discrimination task with 24-h intertrial intervals (24-h ITI task) develops a few weeks earlier in female than in male infant monkeys3. To test whether this sex difference was related to the presence of perinatal androgens, plasma testosterone levels were reduced in male infant monkeys by neonatal orchiectomy and increased in neonatally ovariectomized female infant monkeys by treatment with either testosterone propionate (TP) or its reduced metabolite, dihydrotestosterone (DHT). At 3 months of age, the animals were tested on the 24-h ITI task and their performance compared with that of age-matched intact male and female monkeys. Orchiectomy which was followed by a slight but visible atrophy of the external genitalia, hastened performance of male infant monkeys to the level of intact infant females. Conversely, androgenization of ovariectomized female infant monkeys given DHT, which had only a slight virilizing effect on the external genitalia, slowed the learning of these female infants to the rate of intact male infant monkeys. Curiously, although TP treatment in ovariectomized female infant monkeys was more effective than DHT in virilizing the external genitalia, it failed to slow the rate of learning. This dissociation between the effects of TP and DHT on external genital organs and learning abilities is discussed in terms of possible differences in dose-dependent, time-dependent, and receptor-binding mechanisms of the two androgens. The present study provides further evidence that early androgen secretions affect the organization not only of brain structures related to primary sexual characteristics but also of those related to learning abilities. C1 NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. NR 21 TC 17 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD OCT 25 PY 1991 VL 45 IS 1 BP 57 EP 63 DI 10.1016/S0166-4328(05)80180-9 PG 7 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA GQ883 UT WOS:A1991GQ88300007 PM 1764205 ER PT J AU XIE, CW MCGINTY, JF LEE, PHK MITCHELL, CL HONG, JS AF XIE, CW MCGINTY, JF LEE, PHK MITCHELL, CL HONG, JS TI A GLUTAMATE ANTAGONIST BLOCKS PERFORANT PATH STIMULATION-INDUCED REDUCTION OF DYNORPHIN PEPTIDE AND PRODYNORPHIN MESSENGER-RNA LEVELS IN RAT HIPPOCAMPUS SO BRAIN RESEARCH LA English DT Article DE GLUTAMATE ANTAGONIST; PERFORANT PATH STIMULATION; DYNORPHIN-A (1-8); PRODYNORPHIN MESSENGER RNA; WET DOG SHAKE; DENTATE GRANULE CELL ID WET DOG SHAKES; ENKEPHALIN-LIKE IMMUNOREACTIVITY; LONG-TERM POTENTIATION; DENTATE GYRUS; DIFFERENTIALLY ALTERS; ENTORHINAL CORTEX; GRANULE CELLS; AMINO-ACIDS; RECEPTORS; BRAIN AB Stimulation of the perforant path elicits a behavioral responses, wet dog shakes (WDS), and reduction in hippocampal dynorphin A(1-8) immunoreactivity (DYN-IR) and prodynorphin mRNA (DYN mRNA) in rats. This study examined whether glutamate, the proposed endogenous transmitter released by perforant fibers, mediated the above responses. A glutamate antagonist, gamma-D-glutamylglycine (DGG, 25-mu-g/0.5-mu-l), or artificial cerebrospinal fluid (ACSF, 0.5-mu-l) was injected into the ventral hippocampus 10-20 min prior to acute or daily stimulation of the left perforant path in rats. In acute stimulation experiments, 4 consecutive stimulation trials elicited a total of 73 +/- 4 WDS at an average threshold intensity of 0.46 +/- 0.03 mA in ACSF-treated rats. The hippocampal DYN-IR in these animals decreased by more than 40% in both dorsal and ventral hippocampus relative to sham-stimulated rats. DGG injections significantly elevated the threshold for WDS (0.78 +/- 0.05 mA, P < 0.01), reduced the number of WDS (45 +/- 6, P < 0.01), and partially antagonized stimulation-induced reduction of DYN-IR in the ventral, but not dorsal, hippocampus. In daily stimulation experiments, rats received a single trial of stimulation once per day for 6 days. Daily DGG pretreatment almost completely abolished WDS at control threshold intensities, and significantly inhibited stimulation-induced decrease of DYN-IR in both dorsal and ventral hippocampus. In situ hybridization using a S-35-labeled oligodeoxyribonucleotide probe demonstrated a clear depletion of DYN mRNA signal in the dentate granule cell layer of ACSF-treated animals. This depletion was completely prevented in DGG-treated rats. These data suggest that glutamate as the endogenous transmitter at perforant synapses regulates the release and biosynthesis of dynorphin peptides in dentate granule cells. C1 NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,POB 12233,MD 1701,RES TRIANGLE PK,NC 27709. E CAROLINA UNIV,SCH MED,DEPT ANAT & CELL BIOL,GREENVILLE,NC 27858. FU NIDA NIH HHS [DA 03982] NR 36 TC 18 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 25 PY 1991 VL 562 IS 2 BP 243 EP 250 DI 10.1016/0006-8993(91)90627-8 PG 8 WC Neurosciences SC Neurosciences & Neurology GA GP151 UT WOS:A1991GP15100008 PM 1685342 ER PT J AU MARLEY, RJ WITKIN, JM GOLDBERG, SR AF MARLEY, RJ WITKIN, JM GOLDBERG, SR TI A PHARMACOGENETIC EVALUATION OF THE ROLE OF LOCAL-ANESTHETIC ACTIONS IN THE COCAINE KINDLING PROCESS SO BRAIN RESEARCH LA English DT Article DE COCAINE; GENETIC; KINDLING; LIDOCAINE; LOCAL ANESTHETIC; SEIZURE; SENSITIZATION; TOLERANCE ID STRUCTURAL REQUIREMENTS; MOUSE-BRAIN; MICE; PROCONVULSANT; AMPHETAMINE; CONGENERS; SEIZURES; INTERACT; BINDING; SITES AB Repeated administration of subconvulsant doses of lidocaine or cocaine results in the development of an increased susceptibility to seizures induced by the two drugs (pharmacological kindling). It has been hypothesized that the local anesthetic properties of cocaine are responsible for its convulsant and epileptogenic actions. As genetic factors appear to mediate acute sensitivity to the convulsant properties of cocaine and the development of cocaine-kindled seizures, the present studies used a pharmacogenetic approach to address this question further. The convulsant effects of lidocaine were evaluated in BALB, C57, DBA and SJL mice and compared with previous studies evaluating cocaine-induced seizures. We have also evaluated the development of lidocaine- versus cocaine-kindled seizures and the effects of repeated treatment with cocaine or lidocaine on subsequent lidocaine seizure susceptibility in three of these inbred mouse strains. As observed for cocaine, genetic factors influence the convulsant properties of lidocaine; however, the differences between the strains of mice in susceptibility to lidocaine-induced seizures (SJL > DBA = BALB = C57) did not parallel those seen for cocaine-induced seizures (C57 > DBA = BALB > SJL). Similarly, the time course for the expression of kindled seizures and the differences between the various inbred strains were not the same for lidocaine kindling and cocaine kindling. However, depending on the genetic background of the subject, the repeated administration of lidocaine, or cocaine, resulted in the development of sensitization or tolerance to the consulvant effects of lidocaine in an identical manner. That is, within each of the inbred strains, the effect of a convulsant dose of lidocaine was the same 72 h after the end of 5 days of cocaine treatment as after 5 days of lidocaine treatment. These results suggest that the local anesthetic properties of cocaine appear to be responsible, at least in part, for its convulsant and epileptogenic properties. However, additional actions of cocaine appear to obscure some of the genetic similarities in response to lidocaine and cocaine. RP MARLEY, RJ (reprint author), NIDA,ADDICT RES CTR,BOX 5180,BALTIMORE,MD 21224, USA. NR 21 TC 26 Z9 26 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 OCT 25 PY 1991 VL 562 IS 2 BP 251 EP 257 DI 10.1016/0006-8993(91)90628-9 PG 7 WC Neurosciences SC Neurosciences & Neurology GA GP151 UT WOS:A1991GP15100009 PM 1773340 ER PT J AU SMITH, QR JOHANSON, CE AF SMITH, QR JOHANSON, CE TI CHLORIDE EFFLUX FROM ISOLATED CHOROID-PLEXUS SO BRAIN RESEARCH LA English DT Article DE CHOROID PLEXUS EPITHELIUM; CEREBROSPINAL FLUID; CL-36 EFFLUX COEFFICIENT; ACETAZOLAMIDE; DISULFONIC STILBENE; FUROSEMIDE; ISETHIONATE; ANION EXCHANGE ID RED BLOOD-CELLS; CEREBROSPINAL-FLUID; TRANSPORT; EXCHANGE; CSF; PH; ACIDOSIS; ACETAZOLAMIDE; FUROSEMIDE; INHIBITION AB Chloride efflux was analyzed in adult rat lateral ventricle choroid plexus (LVCP) incubated in artificial CSF (aCSF) at 37-degrees-C. Following steady-state loading of Cl-36 in LVCP, the tracer release from plexus to aCSF was quantified by the efflux coefficient (k, s-1), equal to ln 2/t1/2. Cl efflux could be described by a 2-component model, with a t1/2 for the 'fast' component matching well that for [H-3]sucrose (extracellular marker) and a slower, drug-inhibitable component of Cl-36 release thought to reflect cellular washout. The cellular Cl efflux was more than twice as fast as 37-degrees-C than at 15-degrees-C. There was progressively more rapid efflux (k) of Cl-36 from cells as the aCSF was altered over a range of several pH values from 6.7 (k = 0.026 s-1) to 8.2 (0.070 s-1). CSF medium anion replacement (isethionate and HEPES for Cl and HCO3, respectively) reduced the k for Cl-36 by 57%. Acetazolamide (0.1 mM) and other Cl transport inhibitors (disulfonic stilbenes and loop diuretic) reduced Cl efflux by 35-55%. Acetazolamide inhibited Cl release from LVCP into aCSF whether the latter contained Cl and HCO3, or not. Overall, the findings suggest that Cl extrusion from choroid plexus is by way of an anion exchanger and via channels. C1 BROWN UNIV,RHODE ISL HOSP,DEPT CLIN NEUROSCI,PROGRAM NEUROSURG,PROVIDENCE,RI 02902. NIA,NEUROSCI LAB,BETHESDA,MD 20892. FU NINDS NIH HHS [NS 27601] NR 31 TC 11 Z9 11 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 25 PY 1991 VL 562 IS 2 BP 306 EP 310 DI 10.1016/0006-8993(91)90636-A PG 5 WC Neurosciences SC Neurosciences & Neurology GA GP151 UT WOS:A1991GP15100017 PM 1773342 ER PT J AU WANG, LQ BALAKIR, R HORTON, WE AF WANG, LQ BALAKIR, R HORTON, WE TI IDENTIFICATION OF A CIS-ACTING SEQUENCE IN THE COLLAGEN-II ENHANCER REQUIRED FOR CHONDROCYTE EXPRESSION AND THE BINDING OF A CHONDROCYTE NUCLEAR FACTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID GENE; CHONDROGENESIS AB Collagen II is synthesized at high levels by differentiated chondrocytes. A 620-base pair DNA sequence in the first intron of the rat collagen II gene was previously determined to have chondrocyte-specific enhancer activity. Using mobility shift assays, we have defined a decamer sequence, 5'-CACAATGCAT-3', in the middle of the enhancer that binds a protein or protein complex expressed by chondrocytes but not by NIH3T3 cells or L2 rat fibroblasts. This protein was also induced during the differentiation of limb bud mesenchymal cells into chondroCytes. Mutational analyses, coupled with both in vitro binding studies and direct assays of enhancer activity following transfection into cells, demonstrated that this sequence is involved in the binding of the chondrocyte nuclear protein(s) and is necessary for the enhancer activity. This sequence has homology to the consensus binding sequence for helix-loop-helix transcription factors. C1 NIA,GERONTOL RES CTR,BIOL CHEM LAB,4940 EASTERN AVE,BALTIMORE,MD 21224. NR 13 TC 37 Z9 37 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 OCT 25 PY 1991 VL 266 IS 30 BP 19878 EP 19881 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GM039 UT WOS:A1991GM03900004 PM 1939051 ER PT J AU LASSMANN, G ODENWALLER, R CURTIS, JF DEGRAY, JA MASON, RP MARNETT, LJ ELING, TE AF LASSMANN, G ODENWALLER, R CURTIS, JF DEGRAY, JA MASON, RP MARNETT, LJ ELING, TE TI ELECTRON-SPIN-RESONANCE INVESTIGATION OF TYROSYL RADICALS OF PROSTAGLANDIN-H SYNTHASE - RELATION TO ENZYME CATALYSIS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HIGHER OXIDATION-STATES; VESICULAR GLAND MICROSOMES; RIBONUCLEOTIDE REDUCTASE; ENDOPEROXIDE SYNTHETASE; PEROXIDASE-ACTIVITIES; COMPLEMENTARY-DNA; HEME; CYCLOOXYGENASE; HYDROPEROXIDE; BIOSYNTHESIS AB We have examined, by low temperature ESR, the protein-derived radicals formed by reaction of purified ram seminal vesicle prostaglandin H synthase (PHS). Upon addition of arachidonic acid or 5-phenyl-4-pentenyl-1-hydroperoxide (PPHP) to PHS reconstituted with Fe(III)-protoporphyrin IX (Fe-PHS) at -12-degrees-C, an ESR spectrum was observed at -196-degrees-C containing a doublet that rapidly converted into a singlet. These protein-derived radicals were identified as tyrosyl radicals. The addition of a peroxidase substrate, phenol, completely abolished the appearance of the doublet and suppressed the formation of the singlet but did not inhibit eicosanoid formation. Incubation of arachidonic acid with PHS reconstituted with Mn(III)-protoporphyrin IX (Mn-PHS) produced only a broad singlet that exhibited different power saturation behavior than the tyrosyl radicals and decayed more rapidly. This broad singlet does not appear to be a tyrosyl radical. No ESR signals were observed on incubation of PPHP with Mn-PHS, which has cyclooxygenase but not peroxidase activity. Eicosanoid synthesis occurred very rapidly after addition of arachidonic acid and was complete within 1 min. In contrast, the protein-derived radicals appeared at a slower rate and after the addition of the substrate reached maximal levels between 1 and 2 min for Fe-PHS and 4-6 min for Mn-PHS. These results suggest that the observed protein-derived radicals are not catalytically competent intermediates in cyclooxygenase catalysis by either Fe-PHS or Mn-PHS. The peroxidase activity appears to play a major role in the formation of the tyrosyl radicals with Fe-PHS. C1 NIEHS, MOLEC BIOPHYS LAB, RES TRIANGLE PK, NC 27709 USA. VANDERBILT UNIV, MED CTR,SCH MED,CTR MOLEC TOXICOL,DEPT BIOCHEM, AB HANCOCK JR MEM LAB CANC RES, NASHVILLE, TN 37232 USA. VANDERBILT UNIV, MED CTR, SCH MED, DEPT CHEM, NASHVILLE, TN 37232 USA. FU NCI NIH HHS [CA-47479] NR 59 TC 94 Z9 94 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 OCT 25 PY 1991 VL 266 IS 30 BP 20045 EP 20055 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GM039 UT WOS:A1991GM03900030 PM 1657911 ER PT J AU MORRISON, DF OBRIEN, PJ PEPPERBERG, DR AF MORRISON, DF OBRIEN, PJ PEPPERBERG, DR TI DEPALMITYLATION WITH HYDROXYLAMINE ALTERS THE FUNCTIONAL-PROPERTIES OF RHODOPSIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OUTER SEGMENT PHOSPHODIESTERASE; C-TERMINAL PEPTIDES; BOVINE RHODOPSIN; RETINAL TRANSDUCIN; RAT RHODOPSIN; ACYLATION; ACID; PROTEOLYSIS; ACTIVATION; PROTEINS AB Rhodopsin, the photosensitive protein found in rod photoreceptors, has two covalently attached palmitates that are thought to anchor a portion of the C terminus to the disc membrane, forming a fourth cytoplasmic loop. Using hydroxylamine (NH2OH) to cleave the thioester linkage, we have characterized the effect of depalmitylation on certain functional properties of rhodopsin. Treatment of rod outer segment membranes (prepared from rat retinas previously labeled in vivo with [H-3]palmitate) with 1 M NH2OH typically removed greater-than-or-equal-to 75% of the [H-3]palmitate initially bound to rhodopsin. Spectrophotometry of rod outer segment membranes that had been treated with 1 M NH2OH indicated preservation of 85% of the native rhodopsin and no effect on the shape of the absorbance spectrum of rhodopsin. In vivo labeled rhodopsin that had been treated with 1 M NH2OH did not reincorporate free endogenous [H-3]palmitate over a 2-h incubation period. Both NH2OH-treated and untreated rhodopsin incorporated [C-14]palmitate from exogenously added [C-14]palmitoyl-CoA. This incorporation was substantially greater in the NH2OH-treated sample. The removal of palmitate by NH2OH inhibited rhodopsin regeneration by 44% and increased the ability of rhodopsin to activate transducin's light-dependent GTPase activity by 61%. However, the removal of palmitate from rhodopsin did not affect the light-dependent binding of transducin (T-alpha and T-beta-gamma). C1 UNIV ILLINOIS,COLL MED,LIONS ILLINOIS EYE RES INST,DEPT OPHTHALMOL & VISUAL SCI,CHICAGO,IL 60612. NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. FU NEI NIH HHS [EY-01792, EY-07038, EY-05494] NR 35 TC 62 Z9 63 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 OCT 25 PY 1991 VL 266 IS 30 BP 20118 EP 20123 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GM039 UT WOS:A1991GM03900039 PM 1939072 ER PT J AU QUINN, CP SINGH, Y KLIMPEL, KR LEPPLA, SH AF QUINN, CP SINGH, Y KLIMPEL, KR LEPPLA, SH TI FUNCTIONAL MAPPING OF ANTHRAX TOXIN LETHAL FACTOR BY IN-FRAME INSERTION MUTAGENESIS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT ADENYLATE-CYCLASE; PROTECTIVE ANTIGEN GENE; BACILLUS-ANTHRACIS; ESCHERICHIA-COLI; EDEMA FACTOR; NUCLEOTIDE-SEQUENCE; MOLECULAR-CLONING; EUKARYOTIC CELLS; EXPRESSION; TRANSFORMATION AB Linker insertion mutagenesis was employed to create structural disruptions of the lethal factor (LF) protein of anthrax toxin to map functional domains. A dodecameric linker was inserted at 17 blunt end restriction enzyme sites throughout the gene. Paired MluI restriction sites within the linker allowed the inserts to be reduced from four to two amino acids. Shuttle vectors containing the mutated genes were transformed into the avirulent Bacillus anthracis UM23C1-1 for expression and secretion of the gene products. Mutations at five sites in the central one-third of the sequence made the protein unstable, and purified protein could not be obtained. Mutated LF proteins with insertions at the other sites were purified and assessed for toxic activity in a macrophage lysis assay and for their ability to bind to the protective antigen (PA) component of anthrax toxin, the receptor binding moiety. Most insertions located in the NH2-terminal one-third of the LF protein eliminated both toxicity and binding to PA, while all four insertions in the COOH-terminal one-third of the protein eliminated toxicity without affecting binding to PA. These data support the hypothesis that the NH2-terminal domain contains the structures required for binding to PA and the COOH-terminal domain contains the putative catalytic domain of LF. C1 NIDR,MICROBIAL ECOL LAB,BLDG 30,RM 309,BETHESDA,MD 20892. NR 52 TC 68 Z9 70 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 OCT 25 PY 1991 VL 266 IS 30 BP 20124 EP 20130 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GM039 UT WOS:A1991GM03900040 PM 1939073 ER PT J AU HEIDARAN, MA PIERCE, JH YU, JC LOMBARDI, D ARTRIP, JE FLEMING, TP THOMASON, A AARONSON, SA AF HEIDARAN, MA PIERCE, JH YU, JC LOMBARDI, D ARTRIP, JE FLEMING, TP THOMASON, A AARONSON, SA TI ROLE OF ALPHA-BETA-RECEPTOR HETERODIMER FORMATION IN BETA-PLATELET-DERIVED GROWTH-FACTOR (PDGF) RECEPTOR ACTIVATION BY PDGF-AB SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE KINASE-ACTIVITY; ONE B-CHAIN; SIGNAL TRANSDUCTION; CDNA CLONING; MAJOR PART; EXPRESSION; PHOSPHORYLATION; DIMERIZATION; ESTABLISHES; SEQUENCE AB We investigated the ability of highly purified recombinant platelet-derived growth factor (PDGF) AB to interact with the products of alpha and beta-receptor genes expressed in cells independently or concurrently. Although PDGF-AB lacked any detectable ability to bind or activate beta-receptors in cells expressing only this receptor, efficient beta-receptor activation by this ligand was readily observed in cells coexpressing alpha-platelet-derived growth factor receptors (alpha-PDGFRs). Beta-receptor activation induced by PDGF-AB was shown to be dependent upon in vivo physical association of this receptor with alpha-PDGFRs. Moreover, cross-linking analysis established the existence of PDGF-AB-induced beta-PDGFR dimers in vivo. All of these findings argue that initial PDGF-AB interaction with the alpha-PDGFR induces conformational changes in the ligand or receptor that facilitates efficient recruitment of beta-PDGFR by this PDGF isoform. C1 NCI,CELLULAR & MOLEC BIOL LAB,BLDG 37,RM 1E24,BETHESDA,MD 20892. AMGEN INC,THOUSAND OAKS,CA 91320. NR 31 TC 59 Z9 59 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 OCT 25 PY 1991 VL 266 IS 30 BP 20232 EP 20237 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GM039 UT WOS:A1991GM03900055 PM 1657917 ER PT J AU JAXEL, C CAPRANICO, G KERRIGAN, D KOHN, KW POMMIER, Y AF JAXEL, C CAPRANICO, G KERRIGAN, D KOHN, KW POMMIER, Y TI EFFECT OF LOCAL DNA-SEQUENCE ON TOPOISOMERASE-I CLEAVAGE IN THE PRESENCE OR ABSENCE OF CAMPTOTHECIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SV40 DNA; BINDING; TRANSCRIPTION; REQUIREMENTS; DOXORUBICIN; BREAKAGE; MOBILITY; INVITRO; COMPLEX; SITES AB In order to investigate the mechanism of topoisomerase I inhibition by camptothecin, we studied the induction of DNA cleavage by purified mammalian DNA topoisomerase I in a series of oligonucleotides and analyzed the DNA sequence locations of preferred cleavage sites in the SV40 genome. The oligonucleotides were derived from the sequence of the major camptothecin-induced cleavage site in SV40 DNA (Jaxel, C., Kohn, K. W., and Pommier, Y. (1988) Nucleic Acids Res. 16, 11157 to 11170) with the cleaved bond in their center. DNA length was critical since cleavage was detectable only in 30 and 20 base pair-(bp) oligonucleotides, but not in a 12-bp oligonucleotide. Cleavage was at the same position in the oligonucleotides as in SV40 DNA. Its intensity was greater in the 30- than in the 20-bp oligonucleotide, indicating that sequences more than 10 bp away from the cleavage site may influence intensity. Camptothecin-induced DNA cleavage required duplex DNA since none of the single-stranded oligonucleotides were cleaved. Analysis of base preferences around topoisomerase I cleavage sites in SV40 DNA indicated that camptothecin stabilized topoisomerase I preferentially at sites having a G immediately 3' to the cleaved bond. Experiments with 30-bp oligonucleotides showed that camptothecin produced most intense cleavage in a complementary duplex having a G immediately 3' to the cleavage site. Weaker cleavage was observed in a complementary duplex in which the 3'G was replaced with a T. The identity of the 3' base, however, did not affect topoisomerase I-induced DNA cleavage in the absence of drug. These results indicate that camptothecin traps preferentially a subset of the enzyme cleavage sites, those having a G immediately 3' to the cleaved bond. This strong preference suggests that camptothecin binds reversibly to the DNA at topoisomerase I cleavage sites, in analogy to a model previously proposed for inhibitors of topoisomerase II (Capranico, G., Kohn, K. W., and Pommier, Y. (1990) Nucleic Acids Res. 18, 6611-6619). C1 NCI,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BLDG 37,RM 5C27,BETHESDA,MD 20892. RI Capranico, Giovanni/K-1678-2014 OI Capranico, Giovanni/0000-0002-8708-6454 NR 28 TC 194 Z9 196 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 OCT 25 PY 1991 VL 266 IS 30 BP 20418 EP 20423 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GM039 UT WOS:A1991GM03900080 PM 1657924 ER PT J AU CASTRONOVO, V TARABOLETTI, G SOBEL, ME AF CASTRONOVO, V TARABOLETTI, G SOBEL, ME TI FUNCTIONAL DOMAINS OF THE 67-KDA LAMININ RECEPTOR PRECURSOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-ADHESION; MESSENGER-RNA; BINDING PROTEIN; CARCINOMA-CELLS; TUMOR CELLS; SEQUENCE; GLYCOPROTEIN; POLYPEPTIDES; FIBRONECTIN; ATTACHMENT AB We report the characterization of two functional domains of the metastasis-associated 67-kDa laminin receptor (67-LR). Using synthetic peptides deduced from the cDNA sequence of the 37-kDa precursor of the laminin receptor (37-LRP) as well as their corresponding affinity-purified polyclonal antibodies, we identified a unique laminin binding site as well as a membrane-associated domain of the receptor. In laminin dot blot and solid phase radioligand assays, a 20 amino acid synthetic peptide (IPCNNKGAHSVGLMWWMLAR, amino acid residues 161-180, designated peptide G) specifically bound to laminin with high affinity (K(d) = 5 x 10(-8) M). Peptide G also specifically eluted the 67-LR from a laminin affinity column. Peptide G and laminin reacted with a 1:1 stoichiometry, suggesting that there is one recognition site on laminin for the peptide G domain. Immunofluorescence studies, performed on permeabilized and nonpermeabilized human A2058 melanoma cells using 10 different affinity-purified antibodies to distinct regions of the 37-LRP, identified an unusually short membrane-associated domain that was consistent with a computer predicted transmembrane domain (residues 86-101). Our data demonstrate for the first time that the 37-LRP has two functional domains consistent with the characteristics of the mature 67-LR. Furthermore, we propose peptide G as a potential inhibitor of tumor cell interactions with laminin. RP CASTRONOVO, V (reprint author), NCI,PATHOL LAB,TUMOR INVAS & METASTASIS SECT,BLDG 10,RM 2A33,BETHESDA,MD 20892, USA. NR 45 TC 115 Z9 117 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 OCT 25 PY 1991 VL 266 IS 30 BP 20440 EP 20446 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GM039 UT WOS:A1991GM03900084 PM 1834645 ER PT J AU MARAIA, RJ AF MARAIA, RJ TI THE SUBSET OF MOUSE B1 (ALU-EQUIVALENT) SEQUENCES EXPRESSED AS SMALL PROCESSED CYTOPLASMIC TRANSCRIPTS SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SIGNAL RECOGNITION PARTICLE; RNA POLYMERASE-III; ALPHA-FETOPROTEIN GENE; 7SL RNA; PROTEIN TRANSLOCATION; ENDOPLASMIC-RETICULUM; SUCCESSIVE WAVES; LINEAGE HISTORY; MESSENGER-RNA; HUMAN GENOME AB B1 (Alu-equivalent) is a murine short interspersed element whose amplification probably involved an RNA intermediate. B1-homologous RNA comprise a population of heterogenous transcripts of questionable function. A cloned B1 is expressed in the injected frog oocyte by RNA polymerase III transcription, ribonucleoprotein formation, post-transcriptional 3'-processing, and nucleocytoplasmic transport. The present study characterizes small cytoplasmic B1 transcripts of mouse cells. Analyses of ten cDNA clones revealed a subset of a high degree of sequence identity (98%) from which a novel consensus was developed. Structural analyses of these RNAs demonstrated a conserved Alu domain originally identified as part of the 7SL RNA within the translational control domain of the signal recognition particle, while this structure was not conserved in the majority of B1s in the sequence database. Furthermore, it was demonstrated that 3'-processing occurred in only a subset of B1 transcripts in-vitro using homologous nuclear extracts, and in the injected oocyte. The data demonstrate that a limited set of B1 sequences are expressed as processed RNA polymerase III-transcripts of a high degree of structural conservation. Although this subset is transcriptionally active, the selective expression may be due to regulation at the levels of processing and cytoplasmic accumulation. Their lack of Poly-(A) or 3'-oligo-(U) tracts argue that these RNAs are unlikely to represent transposition intermediates. Rather, their cytosolic compartmentalization and conservation of a biologically recognized structure, suggests potential involvement in other aspects of cellular metabolism. RP MARAIA, RJ (reprint author), NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD 20892, USA. NR 55 TC 55 Z9 55 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 OCT 25 PY 1991 VL 19 IS 20 BP 5695 EP 5702 DI 10.1093/nar/19.20.5695 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GM698 UT WOS:A1991GM69800032 PM 1945845 ER PT J AU POLYMEROPOULOS, MH RATH, DS XIAO, H MERRIL, CR AF POLYMEROPOULOS, MH RATH, DS XIAO, H MERRIL, CR TI DINUCLEOTIDE REPEAT POLYMORPHISM AT THE HUMAN GENE FOR INSULIN-LIKE GROWTH FACTOR-I (IGFI) SO NUCLEIC ACIDS RESEARCH LA English DT Note RP POLYMEROPOULOS, MH (reprint author), ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,ROOM 131,2700 MARTIN LUTHER KING AVE,WASHINGTON,DC 20032, USA. NR 4 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 OCT 25 PY 1991 VL 19 IS 20 BP 5797 EP 5797 DI 10.1093/nar/19.20.5797-a PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GM698 UT WOS:A1991GM69800061 PM 1945863 ER PT J AU HOFFMAN, BJ MEZEY, E BROWNSTEIN, MJ AF HOFFMAN, BJ MEZEY, E BROWNSTEIN, MJ TI CLONING OF A SEROTONIN TRANSPORTER AFFECTED BY ANTIDEPRESSANTS SO SCIENCE LA English DT Article ID BRAIN GABA TRANSPORTER; BLOOD-PLATELETS; MEMBRANE-VESICLES; UPTAKE INHIBITOR; 5-HYDROXYTRYPTAMINE; EXPRESSION; SYSTEM; CDNA; IMIPRAMINE; DISORDERS AB A complementary DNA clone for a serotonin (5HT) transporter has been isolated from rat basophilic leukemia cells. The complementary DNA sequence predicts a 653-amino acid protein with 12 to 13 putative transmembrane domains. The 5HT transporter has significant homology to the gamma-aminobutyric acid, dopamine, and norepinephrine transporters. Uptake by CV-1 cells expressing the transporter complementary DNA resembles 5HT uptake by platelets and brain synaptosomes; it is sensitive to antidepressants, amphetamine derivatives, and cocaine. C1 SEMMELWEIS UNIV MED,SCH MED,DEPT ANAT 1,H-1085 BUDAPEST 8,HUNGARY. RP HOFFMAN, BJ (reprint author), NIMH,CELL BIOL LAB,BETHESDA,MD 20892, USA. RI Brownstein, Michael/B-8609-2009 NR 34 TC 490 Z9 493 U1 3 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 25 PY 1991 VL 254 IS 5031 BP 579 EP 580 DI 10.1126/science.1948036 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GL799 UT WOS:A1991GL79900053 PM 1948036 ER PT J AU GRONENBORN, AM CLORE, GM AF GRONENBORN, AM CLORE, GM TI SIMILARITY OF PROTEIN-G AND UBIQUITIN - RESPONSE SO SCIENCE LA English DT Note RP GRONENBORN, AM (reprint author), NIDDKD,CHEM PHYS LAB,BLDG 2,BETHESDA,MD 20892, USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 3 TC 8 Z9 8 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 OCT 25 PY 1991 VL 254 IS 5031 BP 581 EP 582 DI 10.1126/science.254.5031.581-a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GL799 UT WOS:A1991GL79900055 ER PT J AU SCHUSTER, CR AF SCHUSTER, CR TI MONITORING THE IMPACT OF COCAINE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP SCHUSTER, CR (reprint author), NIDA,ROCKVILLE,MD, USA. NR 1 TC 3 Z9 4 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 OCT 23 PY 1991 VL 266 IS 16 BP 2273 EP 2273 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GK661 UT WOS:A1991GK66100039 PM 1920729 ER PT J AU SAROFF, HA AF SAROFF, HA TI LIGAND-DEPENDENT AGGREGATION AND COOPERATIVITY - A CRITIQUE SO BIOCHEMISTRY LA English DT Article ID HUMAN-HEMOGLOBIN; PROTEINS; LINKAGE AB Ligand-dependent site-site (or subunit-subunit) interactions provide the basis for explaining cooperativity in chemical reactions. Even in the simplest possible nonaggregating system, interpretation of the interactions in terms of structural details requires an explicit assumption (or model) for the binding of the ligand to the sites when there are no interactions. This paper develops in detail the processes by which aggregation will yield ligand-dependent cooperativity. Two conceptually distinct free energy differences may contribute to cooperativity in an aggregation reaction. One is the free energy difference in ligand binding between the monomer and the aggregate. The other is derived from ligand-dependent interactions between the sites of the aggregate. In this analysis an explicit distinction is made between the experimentally accessible constants and those derived from assumed models. Experimental measurements of an aggregation cycle in which all of the species in equilibrium are defined do not allow for an evaluation of the energies of interaction without some model (or assumption). In the analysis presented, an explicit assumption is employed relating the constant for binding of the ligand to the isolated monomer and the constant for the binding of the ligand to aggregate under conditions where there are no ligand-dependent interactions. RP SAROFF, HA (reprint author), NIDDKD,BIOCHEM PHARMACOL LAB,BLDG 8,ROOM 227,BETHESDA,MD 20892, USA. NR 22 TC 6 Z9 6 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 OCT 22 PY 1991 VL 30 IS 42 BP 10085 EP 10090 DI 10.1021/bi00106a004 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GL468 UT WOS:A1991GL46800004 PM 1931940 ER PT J AU TRULLAS, R FOLIO, T YOUNG, A MILLER, R BOJE, K SKOLNICK, P AF TRULLAS, R FOLIO, T YOUNG, A MILLER, R BOJE, K SKOLNICK, P TI 1-AMINOCYCLOPROPANECARBOXYLATES EXHIBIT ANTIDEPRESSANT AND ANXIOLYTIC ACTIONS IN ANIMAL-MODELS SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE ACPC (1-AMINOCYCLOPROPANECARBOXYLIC ACID); NMDA (N-METHYL-D-ASPARTATE); STRYCHNINE-INSENSITIVE GLYCINE RECEPTORS; PLUS-MAZE; FORCED SWIMMING TEST ID NMDA RECEPTOR COMPLEX; RAT-BRAIN; ANTICONVULSANT ACTIVITY; COMPETITIVE ANTAGONIST; FUNCTIONAL ANTAGONISTS; RECOGNITION SITES; CHANNEL COMPLEX; MK-801 BINDING; ION CHANNEL; GLYCINE AB 1-Aminocyclopropanecarboxylic acid (ACPC) is a high affinity ligand at strychnine-insensitive glycine receptors that exhibits partial agonist properties in both biochemical and electrophysiological measures. While ACPC was reported active in animal models commonly used to evaluate potential antidepressants (forced swim) and anxiolytics (plus-maze), the zwitterionic character of this compound could limit both penetration into the central nervous system and oral availability. The present experiments were designed to determine the duration of action of ACPC, its efficacy following oral administration, and to compare these effects with the more lipophilic ACPC methyl ester. Parenterally and orally administered ACPC were equipotent in reducing immobility in the forced swim test, an action manifested for at least 6 h. Both orally and parenterally administered ACPC methyl ester were approximately 3.3-fold more potent than ACPC in the forced swim test. In the elevated plus-maze, both ACPC and ACPC methyl ester were active for 1-2 h after parenteral administration. These findings suggest that 1-aminocyclopropanecarboxylates may constitute a novel class of antidepressant/anxiolytic agents. RP TRULLAS, R (reprint author), NIDDK,NEUROSCI LAB,BLDG 8,ROOM 103,BETHESDA,MD 20892, USA. RI Trullas, Ramon/D-2197-2016 OI Trullas, Ramon/0000-0001-7951-9881 NR 37 TC 93 Z9 94 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD OCT 22 PY 1991 VL 203 IS 3 BP 379 EP 385 DI 10.1016/0014-2999(91)90894-V PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GP608 UT WOS:A1991GP60800008 PM 1685448 ER PT J AU MICHELS, KM SAAVEDRA, JM AF MICHELS, KM SAAVEDRA, JM TI DIFFERENTIAL DEVELOPMENT OF INSULIN-LIKE GROWTH FACTOR-I BINDING IN THE HYPOTHALAMUS OF HAMSTER AND RAT SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE INSULIN-LIKE GROWTH FACTOR; SUPRACHIASMATIC NUCLEUS; MEDIAN EMINENCE; RODENT BRAIN; BRAIN DEVELOPMENT ID CENTRAL NERVOUS-SYSTEM; MEDIAN-EMINENCE; QUANTITATIVE AUTORADIOGRAPHY; BRAIN; RECEPTORS; PITUITARY; LOCALIZATION; NUCLEUS; SITES AB We investigated the binding of [125]insulin-like growth factor-I ([I-125]IGF-I) within the hamster suprachiasmatic nucleus (SCN) and median eminence (ME) by quantitative autoradiography and compared the development of binding to the same regions in the rat. Binding in the hamster SCN was to a single class of sites (estimated K(d) = 6 x 10(-10) M). Binding in the ME was approx. 1.5-fold that of the SCN. Full displacement of binding from the SCN and ME of adults and neonates was achieved by 10(-8) M IGF-I, 10(-8) M IGF-II or 10(-6) M insulin. Binding within the hamster SCN was evident by E15, peaked between P5 and P7 and decreased to adult levels by P20 while binding in the rat SCN peaked perinatally and declined to adult levels by P6. Binding in the hamster ME was evident at P4, peaked by P12 and decreased to adult levels by P20 while binding in rat ME was present by P2, peaked by P7 and declined to adult levels by P9. These results demonstrate a different developmental time course for [I-125]IGF-I binding between the SCN and ME of hamster and rat. The peak binding in the SCN of each species correlates with previously reported time courses for onset of retinohypothalamic innervation of the SCN. Further study of IGFs in these regions may help elucidate the developmental role of brain IGFs. RP MICHELS, KM (reprint author), NIMH,CLIN SCI LAB,PHARMACOL SECT,BLDG 10,ROOM 2D-45,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 22 TC 6 Z9 6 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 OCT 21 PY 1991 VL 62 IS 2 BP 215 EP 221 DI 10.1016/0165-3806(91)90168-I PG 7 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA GQ086 UT WOS:A1991GQ08600007 ER PT J AU RUGGIERO, M WANG, LM PIERCE, JH AF RUGGIERO, M WANG, LM PIERCE, JH TI MITOGENIC SIGNAL TRANSDUCTION IN NORMAL AND TRANSFORMED 32D HEMATOPOIETIC-CELLS SO FEBS LETTERS LA English DT Article DE HEMATOPOIETIC CELL; GROWTH FACTOR; ONCOGENE; INOSITOL LIPID; DIACYLGLYCEROL; PHOSPHATIDYLCHOLINE; SIGNALING ID PROTEIN-KINASE-C; INOSITOL LIPID TURNOVER; PHOSPHATIDIC-ACID; DIACYLGLYCEROL PRODUCTION; PHOSPHOLIPASE-C; GROWTH-FACTORS; RAS; PROLIFERATION; INTERLEUKIN-3; RECEPTORS AB We studied mitogenic signal transduction in normal and oncogene-transformed 32D cells, a murine hematopoietic cell line that is normally dependent on interleukin-3 (IL3) for proliferation and survival. The formation of second messengers was measured in normal cells stimulated with IL3, and in cells transfected with foreign growth factor receptor genes and stimulated with appropriate growth factors. We also measured the steady-state level of second messengers in 32D cells transformed by erbB, abl, and src oncogenes which abrogate growth factor requirement. We found that IL3 stimulated the formation of diacylglycerol independently of inositol lipid turnover, but concomitantly with increased turnover of phosphatidylcholine. Epidermal growth factor (EGF), and platelet-derived growth factor (PDGF) stimulated the 'classical' turnover of inositol lipids with formation of diacylglycerol and calcium-mobilizing inositol phosphates. Colony stimulating factor-1 trigged inositol lipid turnover, although to a much lower extent than EGF and PDGF. Transformed cells showed elevated levels of diacylglycerol together with increased turnover of phosphoinositides and phosphatidylcholine. Taken together these results indicate that different growth factors and oncoproteins associate with multiple signalling pathways in 32D cells. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NR 31 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD OCT 21 PY 1991 VL 291 IS 2 BP 203 EP 207 DI 10.1016/0014-5793(91)81284-F PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA GN100 UT WOS:A1991GN10000011 PM 1936266 ER PT J AU SCOTTO, J PITCHER, H LEE, JAH AF SCOTTO, J PITCHER, H LEE, JAH TI INDICATIONS OF FUTURE DECREASING TRENDS IN SKIN-MELANOMA MORTALITY AMONG WHITES IN THE UNITED-STATES SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID MALIGNANT-MELANOMA; SUN EXPOSURE; AGE; ULTRAVIOLET; HABITS; COHORT; RATES AB Trends in skin melanoma death rates during a 35-year period, 1950-84, were analyzed according to age, sex, and birth cohort for whites in the United States. In contrast to upward trends observed for older men and women (i.e., over 40), downward trends were noted for younger age groups. The risk of dying from skin melanoma appears to have peaked for male cohorts born during the 1950s and for female cohorts born during the 1930s. Assuming no future environmental or lifestyle changes, the upward trend in age-adjusted mortality rates, which averaged 2 to 3% per annum since 1950, is projected to discontinue and bend downward by the second decade of the 21st century. Skin melanoma incidence data, which was limited to a series of 12 years (1973-84) and inadequate for cohort analyses, were included to demonstrate that trends in age-specific rates were comparable with those observed for mortality during the overlapping time period. Incidence trends according to anatomical site are also described. These results indicate that baseline data necessary for assessing the potential effects on this disease from future depletions of the ozone layer, and predicted increases of solar ultra-violet radiation exposure, would be improved with the inclusion of cohort data and age-specific trend analyses. C1 US EPA,WASHINGTON,DC 20460. UNIV WASHINGTON,SEATTLE,WA 98195. RP SCOTTO, J (reprint author), NCI,BETHESDA,MD 20892, USA. NR 29 TC 76 Z9 76 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 OCT 21 PY 1991 VL 49 IS 4 BP 490 EP 497 DI 10.1002/ijc.2910490403 PG 8 WC Oncology SC Oncology GA GL721 UT WOS:A1991GL72100002 PM 1917147 ER PT J AU IYENGAR, S LEVINE, PH ABLASHI, D NEEQUAYE, J PEARSON, GR AF IYENGAR, S LEVINE, PH ABLASHI, D NEEQUAYE, J PEARSON, GR TI SEROEPIDEMIOLOGIC INVESTIGATIONS ON HUMAN HERPESVIRUS-6 (HHV-6) INFECTIONS USING A NEWLY DEVELOPED EARLY ANTIGEN-ASSAY SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID EPSTEIN-BARR-VIRUS; HBLV HUMAN HERPESVIRUS-6; LYMPHOPROLIFERATIVE DISORDERS; IDENTIFICATION; PREVALENCE; LYMPHOMA; ANTIBODY; SEROEPIDEMIOLOGY; SEQUENCES; CHILDREN AB Monoclonal antibodies (MAbs) were developed against immunodominant HHV-6 (GS isolate) late and early proteins. The major late protein was identified as a probable glycoprotein with a molecular weight of approximately 110 kDa (gp 110). Immunoblotting of the early antigen yielded proteins of 41 and 38 kDa (p41/38). The MAb to the early protein reacted with cells infected with 14 different HHV-6 isolates. In contrast, the MAb against the late protein reacted with only 10 of these isolates, indicating that there was strain variation in this glycoprotein. The percentage of antibody-positive sera reactive with gp 110 in the ELISA ranged from 56% to 96% among the different serum donor categories. In contrast, only 10-30% of the sera were positive for antibodies to p41/38 with the exception of sera from patients with African Burkitt's lymphoma (ABL) and Hodgkin's disease (HD). These antibody patterns denote the presence of active HHV-6 replication in patients with ABL and HD. C1 GEORGETOWN UNIV,MED CTR,DEPT MICROBIOL,WASHINGTON,DC 20007. NCI,DIV CANC ETIOL,BETHESDA,MD 20892. BURKITT TUMOR PROJECT,ACCRA,GHANA. NR 34 TC 43 Z9 43 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 OCT 21 PY 1991 VL 49 IS 4 BP 551 EP 557 DI 10.1002/ijc.2910490413 PG 7 WC Oncology SC Oncology GA GL721 UT WOS:A1991GL72100012 PM 1655663 ER PT J AU LICHT, T FIEBIG, HH BROSS, KJ HERRMANN, F BERGER, DP SHOEMAKER, R MERTELSMANN, R AF LICHT, T FIEBIG, HH BROSS, KJ HERRMANN, F BERGER, DP SHOEMAKER, R MERTELSMANN, R TI INDUCTION OF MULTIPLE-DRUG RESISTANCE DURING ANTINEOPLASTIC CHEMOTHERAPY INVITRO SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID HUMAN-TUMOR XENOGRAFTS; P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE; CELL-LINES; HEPATOCELLULAR CARCINOMAS; MONOCLONAL-ANTIBODIES; RAT-LIVER; MDR1 GENE; EXPRESSION; OVEREXPRESSION AB Induction of P-glycoprotein-related multi-drug-resistance (MDR) has been shown in normal and malignant tissues to result from environmental stresses such as heat shock, exposure to carcinogens or X-ray irradiation. To identify conditions under which MDR is enhanced during anti-neoplastic chemotherapy, a cell line showing low-level intrinsic MDR was investigated. In the pleural mesothelioma cell line, PXF1118, < 1% of cells expressed P-glycoprotein (P-gp), as shown by immunocytochemical staining with monoclonal antibody (MAb) MRK16. Exposure of PXF1118 to vincristine, vindesine, vinblastine or doxorubicin for 2-3 weeks led to an increase in the MDR cell fraction of up to 15-28% during 2 to 3 weeks. For doxorubicin and vindesine, dose-dependence was observed: drug concentrations not capable of eliciting cytotoxicity failed to induce significant P-gp expression. Nutrient starvation in aging medium, exposure to activated cyclophosphamide (even at high concentrations) or cisplatin caused only negligible MDR induction. After exposure to vindesine for 6 weeks, tumor colonies exhibited highly enhanced resistance to Vinca alkaloids, doxorubicin, etoposide and dacarbacine, whereas their sensitivity to mitomycin, activated cyclophosphamide or cisplatin remained unchanged. As determined by [H-3]-thymidine uptake and proliferation antigen expression, induction of MDR phenotype was observed at minimal proliferative activity with no change in cell count during exposure to anti-cancer drugs, thus suggesting that the drug treatments changed the phenotype of the cells rather than selecting for a resistant sub-population. In addition, changes in cell differentiation were observed during MDR induction. Induction of P-gp during exposure to anti-cancer drugs thus provides a model for MDR development during initially successful chemotherapy. C1 NCI,FREDERICK,MD 21701. RP LICHT, T (reprint author), UNIV FREIBURG,MED KLIN,DEPT INTERNAL MED,HUGSTETTER STR 55,W-7800 FREIBURG,GERMANY. NR 23 TC 49 Z9 49 U1 1 U2 3 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 OCT 21 PY 1991 VL 49 IS 4 BP 630 EP 637 DI 10.1002/ijc.2910490427 PG 8 WC Oncology SC Oncology GA GL721 UT WOS:A1991GL72100026 PM 1917165 ER PT J AU SHOELSON, SE CHATTERJEE, S CHAUDHURI, M BURKE, TR AF SHOELSON, SE CHATTERJEE, S CHAUDHURI, M BURKE, TR TI SOLID-PHASE SYNTHESIS OF NONHYDROLYZABLE PHOSPHOTYROSYL PEPTIDE ANALOGS WITH N-ALPHA-FMOC-(O,O-DI-TERT-BUTYL)PHOSPHONO-PARA-METHYLPHENYLALANINE SO TETRAHEDRON LETTERS LA English DT Article DE PHOSPHOTYROSINE; TYROSINE KINASE; PROTEIN TYROSINE PHOSPHATASE; ENZYME INHIBITOR; PEPTIDE SYNTHESIS ID INSULIN-RECEPTOR; PHOSPHATASES AB A new, protected derivative of phosphonomethylphenylalanine is used to synthesize nonhydrolyzable analogs of phosphotyrosyl peptides for use as inhibitors and affinity ligands of proteins that recognize phosphotyrosyl sequences. C1 BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NCI,MED CHEM LAB,BETHESDA,MD 20892. RP SHOELSON, SE (reprint author), BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02115, USA. RI Burke, Terrence/N-2601-2014 NR 19 TC 37 Z9 37 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD OCT 21 PY 1991 VL 32 IS 43 BP 6061 EP 6064 DI 10.1016/0040-4039(91)80753-S PG 4 WC Chemistry, Organic SC Chemistry GA GL927 UT WOS:A1991GL92700003 ER PT J AU POWERS, R CLORE, GM BAX, A GARRETT, DS STAHL, SJ WINGFIELD, PT GRONENBORN, AM AF POWERS, R CLORE, GM BAX, A GARRETT, DS STAHL, SJ WINGFIELD, PT GRONENBORN, AM TI SECONDARY STRUCTURE OF THE RIBONUCLEASE-H DOMAIN OF THE HUMAN-IMMUNODEFICIENCY-VIRUS REVERSE-TRANSCRIPTASE IN SOLUTION USING 3-DIMENSIONAL DOUBLE AND TRIPLE RESONANCE HETERONUCLEAR MAGNETIC-RESONANCE SPECTROSCOPY SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Note DE HIV-1; RNASE-H DOMAIN; REVERSE TRANSCRIPTASE; SOLUTION SECONDARY STRUCTURE; 3D HETERONUCLEAR NMR; DOUBLE AND TRIPLE RESONANCE NMR ID NMR-SPECTROSCOPY; C-13-LABELED PROTEINS; PRACTICAL ASPECTS; ESCHERICHIA-COLI; LARGER PROTEINS; ASSIGNMENT; SPECTRA; HIV-1; C-13; INTERLEUKIN-1-BETA C1 NIDDKD,CHEM PHYS LAB,BLDG 2,BETHESDA,MD 20892. NIH,OFF DIRECTOR,PROT EXPRESS LAB,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 38 TC 33 Z9 33 U1 0 U2 3 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 OCT 20 PY 1991 VL 221 IS 4 BP 1081 EP 1090 DI 10.1016/0022-2836(91)90920-2 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GN210 UT WOS:A1991GN21000005 PM 1719214 ER PT J AU SERAFINI, T ORCI, L AMHERDT, M BRUNNER, M KAHN, RA ROTHMAN, JE AF SERAFINI, T ORCI, L AMHERDT, M BRUNNER, M KAHN, RA ROTHMAN, JE TI ADP-RIBOSYLATION FACTOR IS A SUBUNIT OF THE COAT OF GOLGI-DERIVED COP-COATED VESICLES - A NOVEL ROLE FOR A GTP-BINDING PROTEIN SO CELL LA English DT Article ID YPT1 GENE-PRODUCT; ADENYLATE-CYCLASE; ENDOPLASMIC-RETICULUM; CHOLERA-TOXIN; REGULATORY COMPONENT; SUCCESSIVE COMPARTMENTS; VESICULAR TRANSPORT; NUCLEOTIDE-BINDING; SECRETORY VESICLES; MOLECULAR-CLONING AB ADP-ribosylation factor (ARF) is an abundant and highly conserved low molecular weight GTP-binding protein that was originally identified as a key element required for the action of cholera toxin in mammalian cells, but whose physiological role is unknown. We report that ARF family proteins are highly concentrated in non-clathrin-coated transport vesicles and are coat proteins. About three copies of ARF are present on the outside of coated vesicles per alpha-COP (and thus per coatomer). ARF is highly enriched in coated vesicles as compared with parental Golgi cisternae, as shown both by biochemical and morphological methods, and ARF is removed from transport vesicles through uncoating during transport. Furthermore, ARF binds to Golgi cisternae in a GTP-dependent manner independently of coated vesicle budding. These observations strongly suggest a new role for GTP-binding proteins: ARF proteins may modulate vesicle budding and uncoating through controlled GTP hydrolysis. C1 PRINCETON UNIV,DEPT MOLEC BIOL,LEWIS THOMAS LABS,PRINCETON,NJ 08544. UNIV GENEVA,INST HISTOL & EMBRYOL,DEPT MORPHOL,CH-1211 GENEVA 4,SWITZERLAND. NCI,DIV CANC TREATMENT,BIOL CHEM LAB,BETHESDA,MD 20892. RP SERAFINI, T (reprint author), STANFORD UNIV,BECKMAN CTR,DEPT BIOCHEM,STANFORD,CA 94305, USA. FU NCI NIH HHS [CA47767-01A1] NR 69 TC 478 Z9 484 U1 2 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD OCT 18 PY 1991 VL 67 IS 2 BP 239 EP 253 DI 10.1016/0092-8674(91)90176-Y PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GL470 UT WOS:A1991GL47000004 PM 1680566 ER PT J AU DERR, LK STRATHERN, JN GARFINKEL, DJ AF DERR, LK STRATHERN, JN GARFINKEL, DJ TI RNA-MEDIATED RECOMBINATION IN SACCHAROMYCES-CEREVISIAE SO CELL LA English DT Article ID YEAST RETROTRANSPOSON TY; LONG TERMINAL REPEATS; VIRUS-LIKE PARTICLES; SACCHAROMYCES-CEREVISIAE; REVERSE TRANSCRIPTION; ELEMENT TRANSPOSITION; EUKARYOTIC GENOME; GENE-EXPRESSION; CDNA GENES; SPT3 GENE AB The existence of pseudogenes and the observation of intron loss suggest that RNA can serve as an intermediate in recombination. We used a HIS3 reporter gene to show that RNA-mediated recombination occurs in yeast. His3+ prototroph formation required transcription and expression of the retrotransposon Ty. Two RNA-mediated recombination events were detected: homologous recombination between the cDNA and plasmid his3 sequences, resulting in intron loss, and insertion of the cDNA into the chromosome in the absence of HIS3 homology. The chromosomal His3+ prototrophs showed many hallmarks of naturally occurring pseudogenes. They integrated at novel sites in the chromosome, lacked introns, and possessed poly(A) tracts. Additionally, their 5' ends corresponded with the site of initiation of the GAL1 transcript. RP NCI, FREDERICK CANC RES FACIL, EUKARYOT GENE EXPRESS LAB, FREDERICK, MD 21701 USA. FU PHS HHS [N01-C0-74101] NR 36 TC 95 Z9 96 U1 1 U2 8 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 OCT 18 PY 1991 VL 67 IS 2 BP 355 EP 364 DI 10.1016/0092-8674(91)90187-4 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GL470 UT WOS:A1991GL47000015 PM 1655280 ER PT J AU LEGOUIS, R HARDELIN, JP LEVILLIERS, J CLAVERIE, JM COMPAIN, S WUNDERLE, V MILLASSEAU, P LEPASLIER, D COHEN, D CATERINA, D BOUGUELERET, L DELEMARREVANDEWAAL, H LUTFALLA, G WEISSENBACH, J PETIT, C AF LEGOUIS, R HARDELIN, JP LEVILLIERS, J CLAVERIE, JM COMPAIN, S WUNDERLE, V MILLASSEAU, P LEPASLIER, D COHEN, D CATERINA, D BOUGUELERET, L DELEMARREVANDEWAAL, H LUTFALLA, G WEISSENBACH, J PETIT, C TI THE CANDIDATE GENE FOR THE X-LINKED KALLMANN SYNDROME ENCODES A PROTEIN RELATED TO ADHESION MOLECULES SO CELL LA English DT Article ID STEROID SULFATASE GENE; AMINO-ACID-SEQUENCE; DISTAL SHORT ARM; IMMUNOGLOBULIN SUPERFAMILY; HYPOGONADOTROPIC HYPOGONADISM; Y-CHROMOSOME; FIBRONECTIN; MEMBER; DELETIONS; BINDING AB Kallmann syndrome associates hypogonadotropic hypogonadism and anosmia and is probably due to a defect in the embryonic migration of olfactory and GnRH-synthesizing neurons. The Kallmann gene had been localized to Xp22.3. In this study 67 kb of genomic DNA, corresponding to a deletion interval containing at least part of the Kallmann gene, were sequenced. Two candidate exons, identified by multiparameter computer programs, were found in a cDNA encoding a protein of 679 amino acids. This candidate gene (ADMLX) is interrupted in its 3' coding region in the Kallmann patient, in which the proximal end of the KAL deletion interval was previously defined. A 5' end deletion was detected in another Kallmann patient. The predicted protein sequence shows homologies with the fibronectin type III repeat. ADMLX thus encodes a putative adhesion molecule, consistent with the defect of embryonic neuronal migration. C1 NIH, NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20892 USA. GENETHON, F-91002 EVRY, FRANCE. CEPH, F-75010 PARIS, FRANCE. FREE UNIV AMSTERDAM HOSP, DEPT PAEDIAT, 1007 MB AMSTERDAM, NETHERLANDS. CNRS, UNITE ONCOL VIRALE, F-94801 VILLEJUIF, FRANCE. RP INST PASTEUR, CNRS, URA 1445, UNITE GENET MOLEC HUMAINE, F-75724 PARIS 15, FRANCE. RI Legouis, Renaud/G-9088-2014 NR 86 TC 514 Z9 522 U1 2 U2 12 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 OCT 18 PY 1991 VL 67 IS 2 BP 423 EP 435 DI 10.1016/0092-8674(91)90193-3 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GL470 UT WOS:A1991GL47000021 PM 1913827 ER PT J AU SONDIK, EJ AF SONDIK, EJ TI CARET STUDY - WOMEN INCLUDED SO SCIENCE LA English DT Letter RP SONDIK, EJ (reprint author), NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892, USA. NR 1 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 18 PY 1991 VL 254 IS 5030 BP 360 EP 360 DI 10.1126/science.1925587 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GK729 UT WOS:A1991GK72900010 PM 1925587 ER PT J AU KARALIS, K SANO, H REDWINE, J LISTWAK, S WILDER, RL CHROUSOS, GP AF KARALIS, K SANO, H REDWINE, J LISTWAK, S WILDER, RL CHROUSOS, GP TI AUTOCRINE OR PARACRINE INFLAMMATORY ACTIONS OF CORTICOTROPIN-RELEASING HORMONE INVIVO SO SCIENCE LA English DT Article ID CENTRAL NERVOUS-SYSTEM; FACTOR-LIKE IMMUNOREACTIVITY; WALL-INDUCED ARTHRITIS; RAT LEYDIG-CELLS; FACTOR RECEPTORS; BETA-ENDORPHIN; LEWIS RATS; BIOCHEMICAL MANIFESTATIONS; INDUCED SECRETION; MOUSE SPLEEN AB Corticotropin-releasing hormone (CRH) functions as a regulator of the hypothalamic-pituitary-adrenal axis and coordinator of the stress response. CRH receptors exist in peripheral sites of the immune system, and CRH promotes several immune functions in vitro. The effect of systemic immunoneutralization of CRH was tested in an experimental model of chemically induced aseptic inflammation in rats. Intraperitoneal administration of rabbit antiserum to CRH caused suppression of both inflammatory exudate volume and cell concentration by approximately 50 to 60 percent. CRH was detected in the inflamed area but not in the systemic circulation. Immunoreactive CRH is therefore produced in peripheral inflammatory sites where, in contrast to its systemic indirect immunosuppressive effects, it acts as an autocrine or paracrine inflammatory cytokine. C1 NIAMSD,ARTHRIT & RHEUMATISM BRANCH,BETHESDA,MD 20892. NIMH,ALCOHOL DRUG ABUSE & MENTAL HLTH ADM,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 57 TC 398 Z9 399 U1 0 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 18 PY 1991 VL 254 IS 5030 BP 421 EP 423 DI 10.1126/science.1925600 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GK729 UT WOS:A1991GK72900046 PM 1925600 ER PT J AU GERMAIN, RN AF GERMAIN, RN TI ANTIGEN PRESENTATION - THE 2ND CLASS STORY SO NATURE LA English DT Editorial Material ID CLASS-I MOLECULES; VIRAL PEPTIDES; COMPLEXES RP GERMAIN, RN (reprint author), NIAID, IMMUNOL LAB, BETHESDA, MD 20892 USA. NR 26 TC 31 Z9 32 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 17 PY 1991 VL 353 IS 6345 BP 605 EP 607 DI 10.1038/353605a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GK672 UT WOS:A1991GK67200040 PM 1833649 ER PT J AU BUSCH, MP MOSLEY, JW ALTER, HJ EPSTEIN, JS AF BUSCH, MP MOSLEY, JW ALTER, HJ EPSTEIN, JS TI CASE OF HIV-1 TRANSMISSION BY ANTIGEN-POSITIVE, ANTIBODY-NEGATIVE BLOOD - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID IMMUNODEFICIENCY-VIRUS TYPE-1; P24 ANTIGEN; DONORS C1 UNIV SO CALIF,LOS ANGELES,CA 90032. NIH,BETHESDA,MD 20892. US FDA,BETHESDA,MD 20892. RP BUSCH, MP (reprint author), IRWIN MEM BLOOD CTR,SAN FRANCISCO,CA 94118, USA. NR 11 TC 6 Z9 6 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 17 PY 1991 VL 325 IS 16 BP 1175 EP 1175 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GK538 UT WOS:A1991GK53800021 ER PT J AU HEALY, B AF HEALY, B TI MONONUCLEAR CELL SECRETORY PRODUCTS CONTRIBUTE TO BONE TURNOVER FOLLOWING OOPHORECTOMY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP HEALY, B (reprint author), NIH,BETHESDA,MD 20892, USA. NR 1 TC 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 OCT 16 PY 1991 VL 266 IS 15 BP 2054 EP 2054 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GJ474 UT WOS:A1991GJ47400008 PM 1920686 ER PT J AU HEALY, B AF HEALY, B TI BONE-MARROW TRANSPLANTATION FOR ADULTS WITH ACUTE LYMPHOBLASTIC-LEUKEMIA SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP HEALY, B (reprint author), NIH,BETHESDA,MD 20892, USA. NR 1 TC 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 OCT 16 PY 1991 VL 266 IS 15 BP 2054 EP 2054 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GJ474 UT WOS:A1991GJ47400006 PM 1920686 ER PT J AU HEALY, B AF HEALY, B TI CHEMOTHERAPY DURING CHILDHOOD DOES NOT ADVERSELY AFFECT OFFSPRING SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP HEALY, B (reprint author), NIH,BETHESDA,MD 20892, USA. NR 1 TC 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 OCT 16 PY 1991 VL 266 IS 15 BP 2054 EP 2054 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA GJ474 UT WOS:A1991GJ47400007 PM 1920686 ER PT J AU AIN, KB REFETOFF, S FEIN, HG WEINTRAUB, BD AF AIN, KB REFETOFF, S FEIN, HG WEINTRAUB, BD TI PSEUDOMALABSORPTION OF LEVOTHYROXINE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Note ID L-THYROXINE; MUNCHAUSENS SYNDROME; THYROID-HORMONE; TRIIODOTHYRONINE; HYPOTHYROIDISM; MALABSORPTION; ABSORPTION; CONVERSION; BYPASS AB Objective. - The issue of patient compliance with pharmacological therapy vs malabsorption of medication was explored in the context of persistent hypothyroidism despite the administration of large doses of levothyroxine sodium. Design. - Retrospective case series. Setting. - Referred care in two large tertiary care centers. Patients. - Four patients, seen within two decades, with clinical and biochemical hypothyroidism while receiving levothyroxine, were evaluated for selective malabsorption of this hormone. Interventions. - Studies included serial measurements of thyroid hormone levels after a loading dose of levothyroxine or liothyronine sodium or evaluation with a double-labeled thyroxine tracer technique. Results were compared with studies of levothyroxine malabsorption in the medical literature. Results. - All patients were ultimately found to have normal (82% to 100%) absorption of oral levothyroxine. There was no evidence that malabsorption of levothyroxine can occur as an isolated abnormality. Conclusions. - Some patients exhibit a factitious disorder suggesting malabsorption of levothyroxine. When treating hypothyroidism, psychiatric issues may result in noncompliance with levothyroxine therapy. C1 NIDDKD,METAB CELLULAR & NUTR ENDOCRINOL BRANCH,BETHESDA,MD. NIDDKD,CLIN ENDOCRINOL BRANCH,BETHESDA,MD. UNIV CHICAGO,DEPT MED,CHICAGO,IL 60637. UNIV CHICAGO,DEPT PEDIAT,CHICAGO,IL 60637. WALTER REED ARMY MED CTR,DEPT CLIN PHYSIOL,WASHINGTON,DC 20307. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NCRR NIH HHS [RR 00055]; NIDDK NIH HHS [DK 15070] NR 29 TC 50 Z9 52 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 OCT 16 PY 1991 VL 266 IS 15 BP 2118 EP 2120 DI 10.1001/jama.266.15.2118 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA GJ474 UT WOS:A1991GJ47400033 PM 1920700 ER PT J AU NAYFIELD, SG KARP, JE FORD, LG DORR, FA KRAMER, BS AF NAYFIELD, SG KARP, JE FORD, LG DORR, FA KRAMER, BS TI POTENTIAL ROLE OF TAMOXIFEN IN PREVENTION OF BREAST-CANCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID MAMMARY-CARCINOMA MODEL; ANTITHROMBIN-III LEVELS; BONE-MINERAL CONTENT; ENDOMETRIAL CARCINOMA; POSTMENOPAUSAL WOMEN; ADJUVANT TAMOXIFEN; FEMALE RATS; PREMENOPAUSAL WOMEN; SERUM-LIPOPROTEINS; ETHINYL ESTRADIOL AB Despite advances in early detection and treatment of breast cancer, primary prevention has not been well explored, especially for women at increased risk of disease due to reproductive factors and family history. There are, however, suggestions that primary prevention of breast cancer may be a realistic objective. Randomized clinical trials of adjuvant therapy for early-stage breast cancer have demonstrated a 35% decrease in contralateral breast cancers among women receiving tamoxifen compared with controls, suggesting a potential role for tamoxifen in chemoprevention of breast cancer in women at increased risk of the disease. Adjuvant therapy studies also demonstrate that tamoxifen is well tolerated by most patients and suggest additional health benefits from alterations in plasma lipid levels and stabilization of bone mineral loss in women receiving tamoxifen. Aspects of tamoxifen pharmacology, laboratory research, and clinical experience which support its investigation as a chemopreventive agent for breast cancer are summarized, and potential toxic effects are discussed. C1 NCI,DIV CANC TREATMENT,CLIN INVEST BRANCH,BETHESDA,MD 20892. RP NAYFIELD, SG (reprint author), NCI,DIV CANC PREVENT & CONTROL,COMMUNITY ONCOL & REHABIL BRANCH,BETHESDA,MD 20892, USA. NR 94 TC 365 Z9 368 U1 0 U2 3 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 16 PY 1991 VL 83 IS 20 BP 1450 EP 1459 DI 10.1093/jnci/83.20.1450 PG 10 WC Oncology SC Oncology GA GK022 UT WOS:A1991GK02200011 PM 1920492 ER PT J AU SMITH, MA UNGERLEIDER, RS HOROWITZ, ME SIMON, R AF SMITH, MA UNGERLEIDER, RS HOROWITZ, ME SIMON, R TI INFLUENCE OF DOXORUBICIN DOSE INTENSITY ON RESPONSE AND OUTCOME FOR PATIENTS WITH OSTEOGENIC-SARCOMA AND EWINGS-SARCOMA SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CITROVORUM FACTOR RESCUE; ADVANCED BREAST-CANCER; 10 YEARS EXPERIENCE; NEOADJUVANT CHEMOTHERAPY; MULTIMODAL THERAPY; ADJUVANT CHEMOTHERAPY; CONTINUOUS INFUSION; PROGNOSTIC FACTORS; COOPERATIVE TRIAL; TUMOR RESPONSE AB The goal of this study was to use dose-intensity analyses of published Ewing's sarcoma and osteogenic sarcoma trials to determine which agents were most closely associated with a favorable response. The percentage of patients with more than 90% tumor necrosis following neoadjuvant chemotherapy was the end point for analysis of osteogenic sarcoma trials, and disease-free survival and percentage of patients with distant-only relapse were the end points for analysis of Ewing's sarcoma trials. The data were analyzed using logistic regression analysis to circumvent the distortion of univariate analysis resulting from the correlation between doxorubicin dose intensity and the dose intensity of other agents. Our analysis suggests that doxorubicin dose intensity is an important determinant of favorable outcome for both Ewing's sarcoma and osteogenic sarcoma and that the dose intensities of other agents do not contribute as significantly to outcome as does doxorubicin dose intensity. Increasing dactinomycin dose intensity was associated with a poorer outcome in treatment of osteogenic sarcoma and Ewing's sarcoma, most likely resulting from regimens with a higher dactinomycin dose intensity having a lower doxorubicin dose intensity. While our analysis of osteogenic sarcoma trials is consistent with significant activity for cisplatin and high-dose methotrexate (and likely ifosfamide), a rank ordering of the efficacy of these agents when given with doxorubicin in multiagent regimens is not possible. Our analysis illustrates the importance of analyzing the contributions of individual agents to combination chemotherapy regimens. In the design of future clinical trials for osteogenic sarcoma and Ewing's sarcoma, careful attention should be given to optimizing doxorubicin dose intensity in regimens to be tested. C1 NCI,DIV CANC TREATMENT,PEDIAT BRANCH,BETHESDA,MD 20892. RP SMITH, MA (reprint author), NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,EXECUT PLAZA N,RM 741,BETHESDA,MD 20892, USA. NR 99 TC 138 Z9 139 U1 1 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 16 PY 1991 VL 83 IS 20 BP 1460 EP 1470 DI 10.1093/jnci/83.20.1460 PG 11 WC Oncology SC Oncology GA GK022 UT WOS:A1991GK02200012 PM 1833556 ER PT J AU AVIS, IL KOVACS, TOG KASPRZYK, PG TRESTON, AM BARTHOLOMEW, R WALSH, JH CUTTITTA, F MULSHINE, JL AF AVIS, IL KOVACS, TOG KASPRZYK, PG TRESTON, AM BARTHOLOMEW, R WALSH, JH CUTTITTA, F MULSHINE, JL TI PRECLINICAL EVALUATION OF AN ANTI-AUTOCRINE GROWTH-FACTOR MONOCLONAL-ANTIBODY FOR TREATMENT OF PATIENTS WITH SMALL-CELL LUNG-CANCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BOMBESIN-LIKE PEPTIDES; ACID-SECRETION; GASTRIN; BRAIN; RAT; IMMUNOREACTIVITY; CARCINOMA; RECEPTORS; PHASE AB We have evaluated an anti-autocrine growth factor monoclonal antibody for potential use in the treatment of patients with small-cell lung cancer. The monoclonal antibody, designated 2A11, binds to the C-terminal region of the autocrine growth factor gastrin-releasing peptide and neutralizes its growth-promoting effects in vitro and in vivo. Equilibrium-binding analysis demonstrated that the peptide binds to the antibody (dissociation constant = 1.5 x 10(-10)) at least as avidly as it binds to the tumor peptide receptor. Pharmacokinetic studies in normal BALB/c mice demonstrated an initial clearance half-life (alpha t1/2) of 24.3 +/- 4 hours and a secondary clearance half-life (beta t1/2) of 1039.6 +/- 309 hours, and biodistribution studies revealed a distribution pattern which generally reflected blood flow. Single intravenous infusions of 2A11 (20 mg/20-25-kg dogs) into normal mongrel dogs with surgically created gastric fistulas antagonized the stimulatory effects of exogenously infused gastrin-releasing peptide or bombesin on plasma gastrin release and gastric acid secretion. Toxicology studies in normal dogs (with gastric fistulas) infused with 50 mg 2A11 intravenously three times a week for 4 weeks failed to reveal any adverse behavioral, clinical, or pathological effects. Four of six dogs developed an immune response to 2A11. Anti-idiotypic antibodies elicited in two cases did not mimic the functional effects of the peptide. We conclude that the concept of immunoblockade of an autocrine growth factor appears feasible in vivo. C1 NATL NAVAL MED CTR, NCI NAVY MED ONCOL BRANCH,BIOTHERAPY SECT,BLDG 8, ROOM 5101, BETHESDA, MD 20889 USA. UNIV CALIF LOS ANGELES, CTR ULCER RES & EDUC, LOS ANGELES, CA 90024 USA. HYBRITECH INC, SAN DIEGO, CA USA. UNIFORMED SERV UNIV HLTH SCI, DEPT MED, BETHESDA, MD 20814 USA. NR 28 TC 31 Z9 31 U1 0 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 16 PY 1991 VL 83 IS 20 BP 1470 EP 1476 DI 10.1093/jnci/83.20.1470 PG 7 WC Oncology SC Oncology GA GK022 UT WOS:A1991GK02200013 PM 1656058 ER PT J AU TARONE, RE HAYES, HM HOOVER, RN ROSENTHAL, JF BROWN, LM POTTERN, LM JAVADPOUR, N OCONNELL, KJ STUTZMAN, RE AF TARONE, RE HAYES, HM HOOVER, RN ROSENTHAL, JF BROWN, LM POTTERN, LM JAVADPOUR, N OCONNELL, KJ STUTZMAN, RE TI SERVICE IN VIETNAM AND RISK OF TESTICULAR CANCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Note ID UNITED-STATES; YOUNG MEN; PET DOGS; VETERANS; MORTALITY; HEALTH; TESTIS C1 WESTAT CORP, ROCKVILLE, MD USA. NCI, SURG BRANCH, DIV CANC TREATMENT, BETHESDA, MD 20892 USA. NATL NAVAL MED CTR, DEPT UROL, BETHESDA, MD 20814 USA. UNIFORMED SERV UNIV HLTH SCI, WALTER REED ARMY MED CTR, BETHESDA, MD 20814 USA. RP TARONE, RE (reprint author), NCI, DIV CANC ETIOL, EPIDEMIOL & BIOSTAT PROGRAM, EXECUT PLAZA N, ROOM 407, BETHESDA, MD 20892 USA. NR 26 TC 20 Z9 20 U1 0 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 16 PY 1991 VL 83 IS 20 BP 1497 EP 1499 DI 10.1093/jnci/83.20.1497 PG 3 WC Oncology SC Oncology GA GK022 UT WOS:A1991GK02200018 PM 1920497 ER PT J AU KLEINMAN, HK AF KLEINMAN, HK TI GROWTH OF HUMAN TUMOR-CELLS IN ATHYMIC MICE - REPLY SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter RP KLEINMAN, HK (reprint author), NIDR,DEV BIOL LAB,BLDG 30,ROOM 414,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 16 PY 1991 VL 83 IS 20 BP 1509 EP 1509 DI 10.1093/jnci/83.20.1509-b PG 1 WC Oncology SC Oncology GA GK022 UT WOS:A1991GK02200025 ER PT J AU ROBERTS, WC EWAYS, EA AF ROBERTS, WC EWAYS, EA TI CLINICAL AND ANATOMIC OBSERVATIONS IN PATIENTS HAVING MITRAL-VALVE REPLACEMENT FOR PURE MITRAL-REGURGITATION AND SIMULTANEOUS TRICUSPID-VALVE REPLACEMENT SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Note ID FEATURES RP ROBERTS, WC (reprint author), NHLBI,PATHOL BRANCH,BETHESDA,MD 20892, USA. NR 11 TC 5 Z9 6 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 15 PY 1991 VL 68 IS 10 BP 1107 EP 1111 DI 10.1016/0002-9149(91)90509-J PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA GL862 UT WOS:A1991GL86200027 PM 1927932 ER PT J AU LOPEZ, JS CHAN, CC BURNIER, M RUBIN, B NUSSENBLATT, RB AF LOPEZ, JS CHAN, CC BURNIER, M RUBIN, B NUSSENBLATT, RB TI IMMUNOHISTOCHEMISTRY FINDINGS IN PRIMARY INTRAOCULAR LYMPHOMA SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Letter ID RETICULUM-CELL SARCOMA RP LOPEZ, JS (reprint author), NEI,IMMUNOL LAB,BLDG 10,RM 10N 226,BETHESDA,MD 20892, USA. NR 4 TC 18 Z9 18 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD OCT 15 PY 1991 VL 112 IS 4 BP 472 EP 473 PG 2 WC Ophthalmology SC Ophthalmology GA GJ131 UT WOS:A1991GJ13100028 PM 1928262 ER PT J AU BATES, SE AF BATES, SE TI CLINICAL-APPLICATIONS OF SERUM TUMOR-MARKERS SO ANNALS OF INTERNAL MEDICINE LA English DT Review DE TUMOR MARKERS, BIOLOGICAL; ANTIGENS, TUMOR-ASSOCIATED, CARBOHYDRATE; ALPHA-FETOPROTEINS; FALSE POSITIVE REACTIONS; FALSE NEGATIVE REACTIONS ID PROSTATE-SPECIFIC ANTIGEN; GERM-CELL TUMORS; HUMAN CHORIONIC-GONADOTROPIN; NEURON-SPECIFIC ENOLASE; EPITHELIAL OVARIAN-CANCER; CARCINOMA-ASSOCIATED ANTIGEN; TISSUE POLYPEPTIDE ANTIGEN; METASTATIC BREAST-CANCER; NONSEMINOMATOUS TESTICULAR CANCER; GESTATIONAL TROPHOBLASTIC DISEASE AB The pursuit of the ideal tumor marker has generated many tests for use in the diagnosis and management of cancer, several of which are now widely available. Tumor markers have five potential uses in patient care: They can be used for screening, for diagnosis, for establishing prognosis, for monitoring treatment, and for detecting relapse. The value of a marker in a given setting depends on two marker-related characteristics-sensitivity and specificity. The value of a marker in a particular malignancy also depends on the effectiveness of therapy for the malignancy. Tumor markers have been used to screen for occult cancer but have proved to be valuable only in selected cancers. As diagnostic tools, tumor markers have limitations: Nearly all markers can be elevated in benign disorders, and most markers are not elevated in the early stages of malignancy. Extreme marker elevation often indicates a poor prognosis and in some malignancies can indicate the need for more aggressive treatment. Tumor markers have their greatest value when used to monitor therapy in patients with widespread cancer. Nearly all markers show some correlation with the clinical course of disease, with marker elevation in any stage declining to normal after a curative intervention. Recurrent disease can be accompanied by increased marker levels, but markers can detect an occult recurrence in only a few diseases, thereby facilitating a second attempt at cure. Although it seems unlikely that an ideal tumor marker will be identified for every malignancy, several workable markers are already available. Increasing our knowledge about the capabilities and limitations of existing markers will enable us to use them judiciously in the treatment of cancer. RP BATES, SE (reprint author), NCI, MED BRANCH, BLDG 10, ROOM 12N226, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 242 TC 176 Z9 179 U1 0 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 15 PY 1991 VL 115 IS 8 BP 623 EP 638 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA GJ902 UT WOS:A1991GJ90200008 PM 1716430 ER PT J AU ALTER, HJ AF ALTER, HJ TI DESCARTES BEFORE THE HORSE - I CLONE, THEREFORE I AM - THE HEPATITIS-C VIRUS IN CURRENT PERSPECTIVE SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE HEPATITIS-C VIRUS; CLONING, MOLECULES; HEPATITIS ANTIBODIES; HEPATITIS, VIRAL, NON-A, NON-B; BLOOD TRANSFUSION ID NON-B-HEPATITIS; HEPATOCELLULAR-CARCINOMA; CIRCULATING ANTIBODIES; PREVALENCE; INFECTION; RISK; HCV AB In an unprecedented approach to viral discovery, the hepatitis C virus (HCV) was cloned before it was established by conventional methods of viral detection or by genomic characterization. Hepatitis C virus is a small (10-kb), single-stranded RNA virus with a genomic organization that places it in the family Flaviviridae. The virus is global in distribution, with a prevalence between 0.3% and 1.5%. The same agent causes parenterally acquired and sporadic non-A, non-B hepatitis. Nonparenteral modes of spread are poorly defined, but low-level sexual transmission is probable. There is a strong association between the presence of antibody to HCV (anti-HCV) and hepatocellular carcinoma; a causal role for HCV is suspected but has not been proved. Hepatitis C virus accounts for at least 85% of the cases of transfusion-associated hepatitis; an anti-HCV-reactive donor was retrospectively identified in nearly 90% of cases. Among donors confirmed by recombinant immunoblot assay (RIBA) to be anti-HCV positive, 80% to 90% are infectious. Hepatitis C virus RNA can be detected within 1 to 2 weeks of exposure and persists throughout the course of infection. Generally, the presence of anti-HCV cannot be confirmed until 9 to 20 weeks after exposure, creating a window period of seronegativity and potential infectivity. It is anticipated that the anti-HCV assay will reduce the number of cases of transfusion-associated hepatitis by 50% in the United States; a 70% reduction has been documented in Spain. C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. RP ALTER, HJ (reprint author), NIH,IMMUNOL SECT,9000 ROCKVILLE PIKE,BLDG 10,ROOM 1C711,BETHESDA,MD 20892, USA. NR 29 TC 104 Z9 105 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 OCT 15 PY 1991 VL 115 IS 8 BP 644 EP 649 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA GJ902 UT WOS:A1991GJ90200010 PM 1654040 ER PT J AU TAKAHASHI, N JETTEN, AM BREITMAN, TR AF TAKAHASHI, N JETTEN, AM BREITMAN, TR TI RETINOYLATION OF CYTOKERATINS IN NORMAL HUMAN EPIDERMAL-KERATINOCYTES SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID RETINOIC ACID RECEPTOR; CDNA SEQUENCE; DIFFERENTIATION; EXPRESSION; PROTEINS; CELLS; ELECTROPHORESIS; IDENTIFICATION; ANTIBODY C1 NIEHS,PULM PATHOBIOL LAB,CELL BIOL SECT,RES TRIANGLE PK,NC 27709. RP TAKAHASHI, N (reprint author), NCI,DIV CANC TREATMENT,BIOL CHEM LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892, USA. OI Jetten, Anton/0000-0003-0954-4445 NR 30 TC 36 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 15 PY 1991 VL 180 IS 1 BP 393 EP 400 DI 10.1016/S0006-291X(05)81306-3 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GL312 UT WOS:A1991GL31200061 PM 1718279 ER PT J AU FISHER, MT AF FISHER, MT TI DIFFERENCES IN THERMAL-STABILITY BETWEEN REDUCED AND OXIDIZED CYTOCHROME-B562 FROM ESCHERICHIA-COLI SO BIOCHEMISTRY LA English DT Article ID ELECTRON-TRANSFER; COMPRESSIBILITY; OXIDATION; PROTEIN; B-562 AB The thermal stabilities of ferri- and ferrocytochrome b562 were examined. Thermally induced spectral changes, monitored by absorption and second-derivative spectroscopies, followed the dissociation of the heme moiety and the increased solvation of tyrosine residue(s) located in close proximity to the heme binding site. All observed thermal transitions were independent of the rate of temperature increase (0.5-2-degrees-C/min), and the denatured protein exhibited partial to near-complete reversibility upon return to ambient temperature. The extent of renaturation of cytochrome b562 is dependent on the amount of time the unfolded conformer is exposed to temperatures above the transition temperature, T(m). All thermally induced spectra changes fit a simple two-state model, and the thermal transition was assumed to be reversible. The thermal transition for ferrocytochrome b562 yielded T(m) and van't Hoff enthalpy (DELTA-H(vH)) values of 81.0-degrees-C and 137 kcal/mol, respectively. In contrast, T(m) and DELTA-H(vH) values obtained for the ferricytochrome were 66.7-degrees-C and 110 kcal/mol, respectively. The estimated increase in the stabilization free energy at the T(m) of ferricytochrome b562 following the one-electron reduction to the ferrous form, where DELTA-DELTA-G = DELTA-T(m)DELTA-S(m) [DELTA-S(m) = 324 cal/(K.mol), DELTA-T(m) = 14.3-degrees-C] [Becktel, W. J., & Schellman, J. A. (1987) Biopolymers 26, 1859-1877], is 4.6 kcal/mol. RP FISHER, MT (reprint author), NHLBI,BIOCHEM LAB,BLDG 3,ROOM 207,BETHESDA,MD 20892, USA. FU NIGMS NIH HHS [GM 33775, GM 31756] NR 29 TC 25 Z9 25 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 OCT 15 PY 1991 VL 30 IS 41 BP 10012 EP 10018 DI 10.1021/bi00105a028 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GK060 UT WOS:A1991GK06000028 PM 1911766 ER PT J AU PELTON, JG TORCHIA, DA MEADOW, ND WONG, CY ROSEMAN, S AF PELTON, JG TORCHIA, DA MEADOW, ND WONG, CY ROSEMAN, S TI H-1, N-15, AND C-13 NMR SIGNAL ASSIGNMENTS OF IIIGLC, A SIGNAL-TRANSDUCING PROTEIN OF ESCHERICHIA-COLI, USING 3-DIMENSIONAL TRIPLE-RESONANCE TECHNIQUES SO BIOCHEMISTRY LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; TWO-DIMENSIONAL NMR; BACTERIAL PHOSPHOTRANSFERASE SYSTEM; QUANTUM COHERENCE SPECTROSCOPY; HISTIDINE-CONTAINING PROTEIN; PHOSPHOCARRIER PROTEIN; LARGER PROTEINS; STAPHYLOCOCCAL NUCLEASE; SALMONELLA-TYPHIMURIUM; SEQUENTIAL ASSIGNMENT AB III(Glc) is an 18.1-kDa signal-transducing phosphocarrier protein of the phosphoenolpyruvate:glycose phosphotransferase system (PTS) of Escherichia coli. Virtually complete (98%) backbone H-1, N-15, and C-13 nuclear magnetic resonance (NMR) signal assignments were determined by using a battery of triple-resonance three-dimensional (3D) NMR pulse sequences. In addition, nearly complete (H-1, 95%; C-13, 85%) side-chain H-1 and C-13 signal assignments were obtained from an analysis of 3D C-13 HCCH-COSY and HCCH-TOCSY spectra. These experiments rely almost exclusively upon one- and two-bond J couplings to transfer magnetization and to correlate proton and heteronuclear NMR signals. Hence, essentially complete signal assignments of this 168-residue protein were made without any assumptions regarding secondary structure and without the aid of a crystal structure, which is not yet available. Moreover, only three samples, one uniformly N-15-enriched, one uniformly N-15/C-13-enriched, and one containing a few types of amino acids labeled with N-15 and/or C-13, were needed to make the assignments. The backbone assignments together with the 3D N-15 NOESY-HMQC and C-13 NOESY-HMQC data have provided extensive information about the secondary structure of this protein [Pelton, J. G., Torchia, D. A., Meadow, N. D., Wong, C.-Y., & Roseman, S. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 3479-3488]. The nearly complete set of backbone and side-chain atom assignments reported herein provide a basis for studies of the three-dimensional structure and dynamics of III(Glc) as well as its interactions with a variety of membrane and cytoplasmic proteins. C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,DEPT BIOL,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,MCCOLLUM PRATT INST,BALTIMORE,MD 21218. FU NIGMS NIH HHS [GM 38759] NR 78 TC 62 Z9 63 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 15 PY 1991 VL 30 IS 41 BP 10043 EP 10057 DI 10.1021/bi00105a032 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GK060 UT WOS:A1991GK06000032 PM 1911770 ER PT J AU HOMMER, DW CLEM, T LITMAN, R PICKAR, D AF HOMMER, DW CLEM, T LITMAN, R PICKAR, D TI MALADAPTIVE ANTICIPATORY SACCADES IN SCHIZOPHRENIA SO BIOLOGICAL PSYCHIATRY LA English DT Article ID SQUARE-WAVE JERKS; EYE-MOVEMENTS; PARKINSONS-DISEASE; RHESUS-MONKEY; SUPERIOR COLLICULUS; SMOOTH-PURSUIT; BASAL GANGLIA; MOTOR CONTROL; REACTION-TIME; PROJECTIONS AB We compared the saccades made by 8 neuroleptic-treated and 7 drug-free schizophrenic inpatients with those made by 11 normal controls during two eye movement tasks. The first task was designed to elicit visually guided but not internally guided saccades. The second task was designed so that optimal performance required saccades be guided on the basis of an internal representation of target behavior. During the first task, schizophrenics made visually guided saccades that were as accurate as those made by control, but both drug-free and neuroleptic-treated schizophrenics made intrusive saccades at a significantly higher rate than control subjects. Most of these maladaptive saccades appeared to be premature attempts to anticipate target jump. During the second eye movement task, which for optimal performance required use of an internal representation to guide eye movements, most patients learned to anticipate target jump as well as controls. However, neuroleptic-treated patients made significantly smaller adaptive anticipatory saccades than either drug-free schizophrenic patients or normal subjects. These finding are discussed as they relate to the prefrontal cortex-basal ganglia circuits involved in the regulation of behavior by representational knowledge and the idea that the abnormal anticipatory saccades we observed represent a failure in the sensorimotor gating of information derived from internal representations. C1 UNIV WASHINGTON,DEPT PSYCHIAT & BEHAV SCI,SEATTLE,WA 98195. NIH,BIOMED ENGN BRANCH,BETHESDA,MD 20892. NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. RP HOMMER, DW (reprint author), VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,1660 S COLUMBIAN WAY,SEATTLE,WA 98108, USA. NR 50 TC 43 Z9 44 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 15 PY 1991 VL 30 IS 8 BP 779 EP 794 DI 10.1016/0006-3223(91)90234-D PG 16 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA GL840 UT WOS:A1991GL84000004 PM 1751621 ER PT J AU RON, E GRIDLEY, G HRUBEC, Z PAGE, W ARORA, S FRAUMENI, JF AF RON, E GRIDLEY, G HRUBEC, Z PAGE, W ARORA, S FRAUMENI, JF TI ACROMEGALY AND GASTROINTESTINAL CANCER SO CANCER LA English DT Article ID GROWTH-HORMONE; COLON CANCER; CARCINOMAS; POLYPS; OLD AB A cohort of 1041 men who were discharged from the hospital with a diagnosis of acromegaly were examined for subsequent cancer. With a mean follow-up time of 8.3 years, an increased rate of cancers of the digestive organs was observed (27 cases; standard incidence ratio [SIR], 2.0; 95% confidence interval [CI], 1.3 to 2.9). Rates were elevated for cancers of the esophagus (7 cases; SIR, 3.1), stomach (4 cases; SIR, 2.5), and colon (13 cases; SIR, 3.1). The increased risk of colon cancer in acromegaly is consistent with previous clinical reports and suggests opportunities for etiologic research and early cancer detection. It would seem prudent to also evaluate this risk in current research on the use of growth hormone in older individuals to increase muscle mass and reduce body fat. C1 NCI,EPIDEMIOL & BIOSTAT PROGRAM,EPN 443,BETHESDA,MD 20892. NATL ACAD SCI,MED FOLLOW UP AGCY,WASHINGTON,DC 20418. NR 25 TC 172 Z9 173 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 OCT 15 PY 1991 VL 68 IS 8 BP 1673 EP 1677 DI 10.1002/1097-0142(19911015)68:8<1673::AID-CNCR2820680802>3.0.CO;2-0 PG 5 WC Oncology SC Oncology GA GH289 UT WOS:A1991GH28900001 PM 1913507 ER PT J AU BAST, RC KNAUF, S EPENETOS, A DHOKIA, B DALY, L TANNER, M SOPER, J CREASMAN, W GALL, S KNAPP, RC ZURAWSKI, VR SCHLOM, J KUFE, DW RITTS, RE AF BAST, RC KNAUF, S EPENETOS, A DHOKIA, B DALY, L TANNER, M SOPER, J CREASMAN, W GALL, S KNAPP, RC ZURAWSKI, VR SCHLOM, J KUFE, DW RITTS, RE TI COORDINATE ELEVATION OF SERUM MARKERS IN OVARIAN-CANCER BUT NOT IN BENIGN DISEASE SO CANCER LA English DT Article ID TUMOR-ASSOCIATED ANTIGEN; PLACENTAL ALKALINE-PHOSPHATASE; ANTIBODY IMMUNORADIOMETRIC ASSAY; MONOCLONAL-ANTIBODY; CA-125 LEVELS; PREOPERATIVE EVALUATION; MALIGNANT DISEASES; BREAST-CANCER; PELVIC MASSES; CARCINOMA AB Effective screening for occult ovarian cancer will require a strategy that is both sensitive and specific. Preliminary data suggest that CA 125 is elevated at diagnosis in a majority of patients with ovarian cancer. Although CA 125 is sufficiently specific to prompt its evaluation as one component of a strategy to detect ovarian cancer in postmenopausal women, a further improvement in specificity would facilitate cost-effective screening. In an attempt to develop a more specific screening strategy, multiple markers were assayed in a panel of sera from 47 patients with ovarian cancer and in a separate panel of sera from 50 individuals with benign disease whose serum CA 125 levels exceeded 35 U/ml. Among the patients with ovarian cancer, elevations of CA 125 (> 35 U/ml) were observed in 91%, CA 15-3 (> 30 U/ml) in 57%, TAG 72 (> 10 U/ml) in 49%, placental alkaline phosphatase (PLAP) in 25%, human milk fat globule protein (HMFG) 1 in 77%, HMFG2 in 62%, and NB/70K in 57%. Among the 50 sera selected from patients with benign disease, CA 125 was more than 35 U/ml in 100% and more than 65 U/ml in 42%. Among those patients with benign disease and elevated CA 125, NB/70K was elevated in 62%, HMFG1 in 26%, and HMFG2 in 12%, whereas TAG 72 and CA 15-3 were elevated in only 6% and 2%, respectively. In addition PLAP appeared promising; elevated enzyme levels were not found in the benign disease group. Among patients with ovarian cancer with CA 125 levels more than 35 U/ml, either TAG 72 or CA 15-3 was elevated in 77%. In the false-positive group, only 6% had elevations of one or the other marker. The CA 125 levels in cancer patients were, however, substantially greater than in patients with benign disease. If sera from patients with ovarian cancer were diluted to a range comparable to that found in benign disease, at least one of the two confirmatory tests was elevated in 63% of the samples from the malignant cases. Consequently, use of CA 15-3 and TAG 72 in combination with CA 125 can increase the apparent specificity of the CA 125 assay for distinguishing malignant from benign disease. Prospective studies will be required to test critically whether the use of additional serum markers in combination with the CA 125 assay would contribute to the specificity of a cost-effective screening strategy for ovarian cancer. C1 CENTOCOR INC,MALVERN,PA. UNIV ROCHESTER,SCH MED,ROCHESTER,NY 14627. HAMMERSMITH HOSP,IMPERIAL CANC RES FUND ONCOL GRP,LONDON W12 0HS,ENGLAND. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NCI,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. DUKE UNIV,MED CTR,DEPT MICROBIOL IMMUNOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT OBSTET & GYNECOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,DUKE COMPREHENS CANC CTR,DURHAM,NC 27710. RP BAST, RC (reprint author), DUKE UNIV,MED CTR,DEPT MED,POB 3843,DURHAM,NC 27710, USA. RI Bast, Robert/E-6585-2011 OI Bast, Robert/0000-0003-4621-8462 FU NCI NIH HHS [5-R01-CA39930, 1-R44-CA40945] NR 48 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 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 1991 VL 68 IS 8 BP 1758 EP 1763 DI 10.1002/1097-0142(19911015)68:8<1758::AID-CNCR2820680819>3.0.CO;2-# PG 6 WC Oncology SC Oncology GA GH289 UT WOS:A1991GH28900018 PM 1913520 ER PT J AU PESCE, C MERINO, MJ CHAMBERS, JT NOGALES, F AF PESCE, C MERINO, MJ CHAMBERS, JT NOGALES, F TI ENDOMETRIAL CARCINOMA WITH TROPHOBLASTIC DIFFERENTIATION - AN AGGRESSIVE FORM OF UTERINE-CANCER SO CANCER LA English DT Article ID HUMAN CHORIONIC-GONADOTROPIN; PRIMARY GASTRIC CHORIOCARCINOMA; TUMOR; ADENOCARCINOMA; METAPLASIA; BLADDER AB Three cases of poorly differentiated endometrial adenocarcinoma showing trophoblast-like differentiation are reported. The multinucleated, syncytiotrophoblast-like cells were strongly positive for beta-human chorionic gonadotropin (beta-HCG) by immunohistochemical study. High levels of beta-HCG were also present in the patients' serum, but dropped significantly after treatment. The patients had an unusually rapid and progressive clinical course with widespread dissemination and death by tumor. C1 NIH,PATHOL LAB,BLDG 10,ROOM 2N212,BETHESDA,MD 20892. YALE UNIV,NEW HAVEN,CT 06520. UNIV GRANADA,GRANADA,SPAIN. NR 18 TC 37 Z9 39 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 OCT 15 PY 1991 VL 68 IS 8 BP 1799 EP 1802 DI 10.1002/1097-0142(19911015)68:8<1799::AID-CNCR2820680825>3.0.CO;2-3 PG 4 WC Oncology SC Oncology GA GH289 UT WOS:A1991GH28900024 PM 1717127 ER PT J AU MEDEIROS, LJ HARRIS, NL AF MEDEIROS, LJ HARRIS, NL TI 4F2 EXPRESSION BY NON-HODGKINS-LYMPHOMA - REPLY SO CANCER LA English DT Letter ID DIFFERENTIATION ANTIGEN EXPRESSION; ACTIVATION C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. RP MEDEIROS, LJ (reprint author), NCI,PATHOL LAB,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 1991 VL 68 IS 8 BP 1860 EP 1860 PG 1 WC Oncology SC Oncology GA GH289 UT WOS:A1991GH28900040 ER PT J AU KHAZAELI, MB SALEH, MN LIU, TP MEREDITH, RF WHEELER, RH BAKER, TS KING, D SECHER, D ALLEN, L ROGERS, K COLCHER, D SCHLOM, J SHOCHAT, D LOBUGLIO, AF AF KHAZAELI, MB SALEH, MN LIU, TP MEREDITH, RF WHEELER, RH BAKER, TS KING, D SECHER, D ALLEN, L ROGERS, K COLCHER, D SCHLOM, J SHOCHAT, D LOBUGLIO, AF TI PHARMACOKINETICS AND IMMUNE-RESPONSE OF I-131 CHIMERIC MOUSE HUMAN-B72.3 (HUMAN LAMBDA-4) MONOCLONAL-ANTIBODY IN HUMANS SO CANCER RESEARCH LA English DT Article ID B72.3; ANTIGEN; TRIAL; IGG; CANCER; ASSAY AB Chimeric B72.3, composed of the V-regions of murine B72.3 and the constant regions of human immunoglobulin G4 heavy and kappa-light chain, was administered as a I-131-labeled conjugate to 12 patients with metastatic colon cancer. Seven of these patients had an antibody response after initial infusion, and the immune response was primarily directed to the murine V-region, although a small proportion of the antibody response was directed to topographical epitopes requiring the presence of both murine V-region and human CH-1 and kappa-constant regions (neo-epitopes). The pharmacokinetics included a plasma disappearance curve best fit by a two-compartmental model with an alpha t1/2 of 18 +/- 7 h and a beta-t1/2 of 224 +/- 66 h. A second infusion of the same dose of I-131-chimeric B72.3 was administered to four of these patients 8 wk after the first infusion. Two patients who had a high antibody response to initial infusion had an anamnestic antibody response, and the infused ch-B72.3 rapidly disappeared from the circulation with associated immune complexes and free I-131 in the plasma. One patient with no initial antibody response had no antibody response and identical pharmacokinetics on second infusion. One patient with a modest transient antibody response to initial infusion had no antibody response on second infusion and a modest shortening of plasma circulation. Thus, the human immunoglobulin G4 isotype chimeric B72.3 monoclonal antibody has a plasma half-life 6 to 8 times as long as murine B72.3 and retains considerable immunogenicity in some patients which can adversely affect repetitive infusions. C1 VET ADM MED CTR,BIRMINGHAM,AL 35233. CELLTECH LTD,SLOUGH,ENGLAND. NCI,BETHESDA,MD 20892. AMER CYANAMID CO,PEARL RIVER,NY 10965. RP KHAZAELI, MB (reprint author), UNIV ALABAMA,CTR COMPREHENS CANC,LB WALLACE TUMOR INST 262B,UAB STN,BIRMINGHAM,AL 35294, USA. FU NCI NIH HHS [R01-CA34232, CM87215]; NCRR NIH HHS [M01-RR00032] NR 31 TC 144 Z9 146 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 OCT 15 PY 1991 VL 51 IS 20 BP 5461 EP 5466 PG 6 WC Oncology SC Oncology GA GJ908 UT WOS:A1991GJ90800003 PM 1913665 ER PT J AU BERG, SL BALIS, FM MCCULLY, CL GODWIN, KS POPLACK, DG AF BERG, SL BALIS, FM MCCULLY, CL GODWIN, KS POPLACK, DG TI PHARMACOKINETICS OF PYRAZOLOACRIDINE IN THE RHESUS-MONKEY SO CANCER RESEARCH LA English DT Article ID I CLINICAL-TRIALS; SELECTIVITY; BINDING; AGENTS AB Pyrazoloacridine is a rationally synthesized acridine derivative with in vitro activity against solid tumor cell lines, noncycling and hypoxic cells, and tumor cell lines that exhibit the multidrug resistance phenotype. The pharmacokinetic behavior of pyrazoloacridine after a 1- or 24-h i.v. infusion was studied in 5 rhesus monkeys that received a total of 10 courses of pyrazoloacridine at 300 or 600 mg/m2. Pyrazoloacridine levels in plasma and cerebrospinal fluid were measured by high-pressure liquid chromatography. For 1-h infusions, the plasma disappearance was biexponential with a t1/2-alpha, of 31 min and t1/2-beta of 11 h. The mean volume of distribution at steady state was 1380 liters/m2. The clearance was 1660 ml/min/m2. For the 300 mg/m2 dose, the mean area under the concentration-time curve was 759-mu-M.min, and the mean peak concentration was 1.3-mu-M. For the 600 mg/m2 dose, the area under the concentration-time curve was 1330-mu-M.min, and the peak concentration was 2.5-mu-M. The steady-state plasma concentrations during the 24-h continuous infusions were 0.27-mu-M for the 300 mg/m2 dose and 0.45-mu-M for the 600 mg/m2 dose. The mean clearance calculated from these steady-state concentrations was 2420 ml/min/m2. Cerebrospinal fluid levels were < 0.1-mu-M for all doses and schedules. There was no evidence of toxicity at any dose or schedule. These results contrast strikingly with those obtained in mice and dogs in which, despite a more rapid clearance of pyrazoloacridine, significant toxicities were observed at doses that were nontoxic in the monkey. These interspecies differences in the pharmacokinetic and pharmacodynamic behavior of pyrazoloacridine have important implications for the design of Phase I trials in humans. RP BERG, SL (reprint author), NCI,PEDIAT BRANCH,BLDG 10,ROOM 13N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 17 TC 20 Z9 20 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 OCT 15 PY 1991 VL 51 IS 20 BP 5467 EP 5470 PG 4 WC Oncology SC Oncology GA GJ908 UT WOS:A1991GJ90800004 PM 1913666 ER PT J AU CASTRONOVO, V TARABOLETTI, G SOBEL, ME AF CASTRONOVO, V TARABOLETTI, G SOBEL, ME TI LAMININ RECEPTOR COMPLEMENTARY DNA-DEDUCED SYNTHETIC PEPTIDE INHIBITS CANCER CELL ATTACHMENT TO ENDOTHELIUM SO CANCER RESEARCH LA English DT Article ID HUMAN-MELANOMA CELLS; FIBRO-SARCOMA CELLS; HUMAN-TUMOR CELLS; EXTRACELLULAR-MATRIX; BINDING PROTEIN; CARCINOMA-CELLS; MESSENGER-RNA; METASTASIS; ADHESION; INTEGRIN AB Stable attachment of cancer cells to the endothelium is a key step in the formation of metastasis. In this study, we have investigated the possibility that interaction between laminin and its M(r) 67,000 high-affinity receptor (67 LR) could play a major role in this process. Scatchard analysis of laminin-binding studies showed that bovine aortic endothelial cells exhibit 46,000 high-affinity receptors that mediate, at least in part, the attachment of highly invasive melanoma cells. This endothelial cell-melanoma cell interaction was significantly inhibited by soluble laminin and by anti-laminin antibodies. Peptide G, an eicosapeptide derived from the complementary DNA sequence of the 67 LR precursor (IPCNNKGAHSVGLMWWMLAR) that specifically binds to laminin and presumably contains the active ligand-binding site of the receptor, specifically prevented attachment of the melanoma cells to both the bovine aortic endothelial cell monolayer and human umbilical vein endothelium. Thus, peptide G may selectively interfere with the metastatic cascade by inhibiting tumor cell attachment to endothelium via the laminin-67 LR pathway and is a potential new antimetastatic agent. RP CASTRONOVO, V (reprint author), NCI,PATHOL LAB,TUMOR INVAS & METASTASIS SECT,BLDG 10,ROOM 2A33,BETHESDA,MD 20892, USA. NR 44 TC 60 Z9 60 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 OCT 15 PY 1991 VL 51 IS 20 BP 5672 EP 5678 PG 7 WC Oncology SC Oncology GA GJ908 UT WOS:A1991GJ90800039 PM 1833053 ER PT J AU SHIMADA, S OGAWA, M SCHLOM, J GREINER, JW AF SHIMADA, S OGAWA, M SCHLOM, J GREINER, JW TI IDENTIFICATION OF A NOVEL TUMOR-ASSOCIATED MR 110,000 GENE-PRODUCT IN HUMAN GASTRIC-CARCINOMA CELLS THAT IS IMMUNOLOGICALLY RELATED TO CARCINOEMBRYONIC ANTIGEN SO CANCER RESEARCH LA English DT Article ID PREGNANCY-SPECIFIC BETA-1-GLYCOPROTEIN; BILIARY GLYCOPROTEIN-I; CEA-RELATED ANTIGENS; MONOCLONAL-ANTIBODIES; DIFFERENTIAL EXPRESSION; MOLECULAR-CLONING; MESSENGER-RNA; HUMAN MAMMARY; FAMILY; CANCER AB A novel gene product which is immunologically related to carcinoembryonic antigen (CEA) and constitutively expressed by six of eight human gastric carcinoma cell lines is described. The antigen was initially identified by the differential binding patterns of four monoclonal antibodies (MAbs) which recognize the putative M(r) 180,000 CEA and/or the M(r) 90,000 CEA-related gene product, NCA (normal cross-reacting antigen). Western blot analyses of partially purified membrane fractions prepared from Hs 746T gastric carcinoma cells identified an M(r) 110,000 antigen. Northern blot analyses using CEA- and NCA-specific complementary DNA probes did not identify any specific CEA or NCA transcripts in polyadenylate-selected mRNA isolated from the Hs 746T cells. Likewise, a probe designed to hybridize with different CEA-related family members failed to identify a CEA-related message in the Hs 746T cells. Subsequent studies revealed that interferon-gamma (IFN-gamma) treatment substantially increased the level of expression of the M(r) 110,000 antigen on the Hs 746T and five other gastric cell types that constitutively expressed the antigen. IFN-gamma-treatment also de novo induced the expression of the M(r) 110,000 antigen on the surface of GaCa gastric carcinoma cells. A high percentage of Hs 746T (ie., > 85%) and GaCa (approximately 75%) gastric carcinoma cells expressed the M(r) 110,000 antigen after IFN-gamma treatment; yet, neither cell type expressed CEA or NCA as measured by the binding of the anti-CEA MAb, COL-1, or B6.2, an anti-NCA MAb. In contrast to CEA and NCA, phosphatidylinositol phospholipase C treatment failed to release the M(r) 110,000 antigen from the surface of the Hs 746T or IFN-gamma-treated GaCa cells, suggesting that membrane attachment of this novel antigen is not via a glycosyl-phosphatidylinositol anchor. Finally, primers that amplify the 420 base pairs of the immunoglobulin-like domain of CEA and NCA detected an appropriately sized product in untreated as well as IFN-gamma-treated GaCa cells using the polymerase chain reaction method. Thus, a potentially novel gene product coding for an M(r) 110,000 antigen that is strongly upregulated by IFN-gamma has been identified in human gastric carcinoma cells. Immunologically, the antigen shares reactive epitopes with CEA and its related NCA gene product; however, Northern blot analyses, polymerase chain reaction, and phosphatidylinositol phospholipase C results suggest that the antigen may be, at best, a distant relative of the CEA gene family. C1 NCI,TUMOR IMMUNOL & BIOL LAB,9000 ROCKVILLE PIKE,BLDG 10,ROOM 8B07,BETHESDA,MD 20892. KUMAMOTO UNIV,SCH MED,DEPT SURG 2,KUMAMOTO 860,JAPAN. NR 44 TC 14 Z9 14 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 OCT 15 PY 1991 VL 51 IS 20 BP 5694 EP 5703 PG 10 WC Oncology SC Oncology GA GJ908 UT WOS:A1991GJ90800042 PM 1913687 ER PT J AU MEZZANZANICA, D GARRIDO, MA NEBLOCK, DS DADDONA, PE ANDREW, SM ZURAWSKI, VR SEGAL, DM WUNDERLICH, JR AF MEZZANZANICA, D GARRIDO, MA NEBLOCK, DS DADDONA, PE ANDREW, SM ZURAWSKI, VR SEGAL, DM WUNDERLICH, JR TI HUMAN LYMPHOCYTES-T TARGETED AGAINST AN ESTABLISHED HUMAN OVARIAN-CARCINOMA WITH A BISPECIFIC F(AB')2 ANTIBODY PROLONG HOST SURVIVAL IN A MURINE XENOGRAFT MODEL SO CANCER RESEARCH LA English DT Article ID PERIPHERAL-BLOOD LYMPHOCYTES; PREVENT TUMOR-GROWTH; MONOCLONAL-ANTIBODIES; RECEPTOR ANTIBODIES; MONONUCLEAR-CELLS; NUDE-MICE; LYSIS; ANTI-T3; ACTIVATION; ANTIGENS AB A bispecific F(ab')2 fragment with anti-CD3 and antitumor specificity was used to target activated human peripheral blood lymphocytes (PBL) against OVCAR-3 human ovarian carcinoma cells growing i.p. in athymic mice. Mice were given injections of OVCAR-3 cells on day 0 and treated with i.p. injections of activated PBL, coated with the [anti-CD3 (TR66) x antitumor (MOv18)] bispecific F(ab')2 on day 4, using an approximate effector:target ratio of 1:1. Treatment was evaluated for the ability either to block tumor growth at 15 days or to prolong survival of tumor-bearing mice. After 15 days, the incidence of mice with tumor growth was 20% among those given PBL coated with bispecific F(ab')2, whereas the incidence among mice untreated or treated with PBL alone or PBL with either parental antibody ranged from 80 to 94%. The mean survival time of tumor-bearing mice treated with PBL, and bispecific F(ab')2 was 104 days, which was 3.5 times that of untreated mice and twice that of mice given PBL alone or PBL with either parental antibody. These results provide support for the concept that treatment of ovarian cancer patients with targeted T-cells could prove beneficial. C1 NIH,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. CENTOCOR INC,MALVERN,PA. HARVARD UNIV,SCH MED,DEPT OBSTET & GYNECOL,BOSTON,MA 02115. RI Mezzanzanica, Delia/C-2607-2017 OI Mezzanzanica, Delia/0000-0002-9664-6871 NR 44 TC 70 Z9 71 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 OCT 15 PY 1991 VL 51 IS 20 BP 5716 EP 5721 PG 6 WC Oncology SC Oncology GA GJ908 UT WOS:A1991GJ90800045 PM 1833054 ER PT J AU SILVERMAN, JA RAUNIO, H GANT, TW THORGEIRSSON, SS AF SILVERMAN, JA RAUNIO, H GANT, TW THORGEIRSSON, SS TI CLONING AND CHARACTERIZATION OF A MEMBER OF THE RAT MULTIDRUG RESISTANCE (MDR) GENE FAMILY SO GENE LA English DT Article DE P-GLYCOPROTEIN; RECOMBINANT DNA; PCR; RODENTS; MOUSE AND HUMAN GENES; GT VECTOR; AFLATOXIN ID P-GLYCOPROTEIN GENE; CLASS-II REGION; BACTERIAL TRANSPORT PROTEINS; COMPLEMENTARY-DNA; CYSTIC-FIBROSIS; EXPRESSION; SEQUENCE; CELLS; PROMOTER; LIVER AB The rat mdr gene family [genes encoding P-glycoprotein (Pgp)] was characterized and the complete sequence of a rat mdr cDNA was determined based on seven independent cDNA clones that correspond to the same gene. The longest of these clones contains a 4.3-kb insert which represents a full-length rat mdr cDNA. The longest open reading frame of this sequence is 3933 bp; the first ATG is at 103 bp, making the deduced protein 1277 amino acids long (141 kDa). This correlates well with previously identified Pgp. The sequence of this gene has a very high, > 90%, degree of identity to the mouse mdr1b gene (also known as the mdr1 gene) therefore, we designate it the rat mdr1b gene. Transcription of this gene begins at a single start point 151 nucleotides upstream from the start codon. We show here that the rat gene family is comprised of three members, which is consistent with previous data on other rodent species. RP SILVERMAN, JA (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BLDG 37,RM 3C25,BETHESDA,MD 20892, USA. NR 36 TC 102 Z9 104 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 OCT 15 PY 1991 VL 106 IS 2 BP 229 EP 236 DI 10.1016/0378-1119(91)90203-N PG 8 WC Genetics & Heredity SC Genetics & Heredity GA GQ121 UT WOS:A1991GQ12100011 PM 1682220 ER PT J AU WATSON, JD AF WATSON, JD TI THE HUMAN GENOME INITIATIVE - A STATEMENT OF NEED SO HOSPITAL PRACTICE LA English DT Article AB We may never have a complete understanding of the complex dynamics of the human organism, but we can and should know all our genes and begin to understand their role in the diseases that diminish our lives. A 15-year program has been projected and the specific, quantifiable goals in mapping and sequencing are outlined. Ethical, legal, and social implications are also discussed. RP WATSON, JD (reprint author), NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892, USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 SN 8750-2836 J9 HOSP PRACT JI Hosp. Pract. PD OCT 15 PY 1991 VL 26 IS 10 BP 69 EP 73 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA GL297 UT WOS:A1991GL29700010 PM 1918207 ER PT J AU HOLZMAN, TF KOHLBRENNER, WE WEIGL, D RITTENHOUSE, J KEMPF, D ERICKSON, J AF HOLZMAN, TF KOHLBRENNER, WE WEIGL, D RITTENHOUSE, J KEMPF, D ERICKSON, J TI INHIBITOR STABILIZATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-2 PROTEINASE DIMER FORMATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SYNTHETIC HIV-1 PROTEASE; RETROVIRAL PROTEASES; CRYSTAL-STRUCTURE; DESIGN AB We report the first direct observation of the subunit self-association behavior of highly purified recombinant human immunodeficiency virus type-2 (HIV-2) proteinase. Multiple samples of enzyme were subjected to sedimentation equilibrium analytical ultracentrifugation sequentially at 8.8-degrees-C and two PH values in the presence and absence of a C2 symmetric, peptidomimetic inhibitor. At both pH values the enzyme exhibited sedimentation equilibrium behavior which fit a monomer-dimer-tetramer model. In the absence of inhibitor, the apparent K(d) for dimer formation was less than approximately 100-mu-M and the apparent K(d) for the weaker dimer-tetramer association was greater than approximately 100-mu-M. In the presence of inhibitor, at either pH, dimer formation was more strongly favored as indicated by a approximately 5-14-fold decrease in the apparent K(d) for dimer formation and a approximately 1.2-4-fold increase in the apparent K(d) for tetramer formation. The enhanced formation of dimer and decrease in higher order self-associated forms in the presence of an inhibitor is consistent with inhibitor stabilization of an active dimer. The inhibitor-induced stabilization of the dimeric species is consistent with a model for substrate-induced formation of active proteinase dimers in virion assembly. C1 ABBOTT LABS,ANTIINFECT RES,ABBOTT PK,IL 60064. ABBOTT LABS,DIV PHARMACEUT PROD,PHARMACEUT DISCOVERY RES,NIH,ANTIVIRAL RES,ABBOTT PK,IL 60064. RP HOLZMAN, TF (reprint author), ABBOTT LABS,PROT BIOCHEM,DEPT 47Z DISCOVERY RES,BLDG AP-10-1,ABBOTT PK,IL 60064, USA. NR 21 TC 23 Z9 23 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 15 PY 1991 VL 266 IS 29 BP 19217 EP 19220 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GK667 UT WOS:A1991GK66700019 PM 1918040 ER PT J AU KOSUGI, S BAN, T AKAMIZU, T KOHN, LD AF KOSUGI, S BAN, T AKAMIZU, T KOHN, LD TI SITE-DIRECTED MUTAGENESIS OF A PORTION OF THE EXTRACELLULAR DOMAIN OF THE RAT THYROTROPIN RECEPTOR IMPORTANT IN AUTOIMMUNE THYROID-DISEASE AND NONHOMOLOGOUS WITH GONADOTROPIN RECEPTORS - RELATIONSHIP OF FUNCTIONAL AND IMMUNOGENIC DOMAINS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GRAVES-DISEASE; MONOCLONAL-ANTIBODIES; SECONDARY STRUCTURE; TSH RECEPTOR; CLONING; AUTOANTIBODIES; EXPRESSION; SEQUENCE; PROTEIN; BINDING AB Residues 287 to 404 of the rat thyrotropin (TSH) receptor exhibit little homology to gonadotropin receptors. A large segment of this region, residues 303-382, has no determinants important for TSH to bind or elevate cAMP levels nor for the activity of thyroid-stimulating autoantibodies (TSAbs) from the sera of Graves' patients, i.e. deletions, substitutions, or mutations in this segment do not result in a loss of any of these activities in transfected Cos-7 cells. Critical residues for these activities do, however, flank both sides of this segment. Of particular interest, deletion or mutation of residues 299-301 and 387-395 results in a marked decrease in high affinity TSH binding but preserves the ability of a TSAb to increase cAMP levels. Tyrosine 385 is also of particular interest since its mutation to phenylalanine, alanine, threonine, or glutamine results in a receptor with a 20-fold decrease in the ability of TSH to bind or increase cAMP levels, but one whose TSAb activity is, once again, preserved. Because one activity is preserved, we can conclude that (a) the receptor must be fully integrated within the membrane of the cell without malfolding, (b) these sequences represent determinants involved in the high affinity TSH binding site, and (c) separate determinants exist for high affinity TSH binding and TSAb activity, consistent with the existence of autoantibodies in Graves' sera which inhibit TSH binding (TBIAbs) or which increase cAMP levels (TSAbs). Additionally, we show that a 16-mer peptide (residues 352-367), which reacts with the sera of > 80% of patients with Graves' disease, can induce the formation of antibodies to a peptide with no sequence homology, residues 377-397. This peptide flanks the region, residues 303-382, with no determinants important for TSH receptor binding or activity. As noted above, it contains residues involved in the high affinity TSH binding site but whose deletion or mutation has no effect on TSAb activity, i.e. residues which would appear to be required at an epitope important for TBIAb but not TSAb antibody activity. RP KOSUGI, S (reprint author), NIDDKD,BIOCHEM & METAB LAB,CELL REGULAT SECT,BETHESDA,MD 20892, USA. NR 26 TC 113 Z9 113 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 OCT 15 PY 1991 VL 266 IS 29 BP 19413 EP 19418 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GK667 UT WOS:A1991GK66700046 PM 1655787 ER PT J AU HAMILTON, SL CODINA, J HAWKES, MJ YATANI, A SAWADA, T STRICKLAND, FM FROEHNER, SC SPIEGEL, AM TORO, L STEFANI, E BIRNBAUMER, L BROWN, AM AF HAMILTON, SL CODINA, J HAWKES, MJ YATANI, A SAWADA, T STRICKLAND, FM FROEHNER, SC SPIEGEL, AM TORO, L STEFANI, E BIRNBAUMER, L BROWN, AM TI EVIDENCE FOR DIRECT INTERACTION OF GS-ALPHA WITH THE CA2+ CHANNEL OF SKELETAL-MUSCLE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CARDIAC CALCIUM CHANNELS; BETA-ADRENERGIC-RECEPTOR; MUSCARINIC K+-CHANNEL; G-PROTEIN-GS; ADENYLYL CYCLASE; 1,4-DIHYDROPYRIDINE RECEPTOR; SUBUNIT COMPOSITION; POTASSIUM CHANNELS; TRANSVERSE TUBULES; BINDING-PROTEIN AB The alpha-subunits of heterotrimeric GTP-binding (G) proteins act upon ion channels through both cytoplasmic and membrane-delimited pathways (Brown, A. M., and Birnbaumer, L. (1990) Annu. Rev. Physiol. 52, 197-213). The membrane pathway may involve either a direct interaction between G protein and ion channel or an indirect interaction involving a membrane-delimited second messenger. To distinguish between the two possibilities, we tested whether a purified G protein could interact with a purified channel protein in a defined system to produce changes in channel currents. We selected the alpha-subunit of G(s) and the dihydropyridine (DHP)-sensitive Ca2+ channel of skeletal muscle T-tubules, the DHP binding protein (DHPBP), because: 1) a membrane-delimited interaction between the two has been shown (Brown, A. M., and Birnbaumer, L. (1990) Annu. Rev. Physiol. 52, 197-213; Yatani, A., Imoto, Y., Codina, J., Hamilton, S. L., Brown, A. M., and Birnbaumer, L. (1988) J. Biol. Chem. 263, 9887-9895); and 2) at the present time, these Ca2+ channels are the only putative G protein channel effectors which, following purification, still retain channel function. We used a defined system in which purified components were studied by direct reconstitution in planar lipid bilayers. Just as we had found in crude skeletal muscle T-tubule membranes (Yatani, A., Imoto, Y., Codina, J., Hamilton, S. L., Brown, A. M., and Birnbaumer, L. (1988) J. Biol. Chem. 263,9887-9895), alpha-s* but not alpha-i-3* stimulated Ca2+ currents. However, in the reconstituted system, this probably represents a direct interaction between G(s)alpha and Ca2+ channels. To establish whether the two proteins were physically associated in the native T-tubule membrane, we examined the ability of either endogenous G proteins or exogenous alpha-s* to purify with detergent-solubilized DHPBP through a wheat germ agglutinin affinity column and a sucrose gradient. Small amounts of a labeled G protein were found to co-purify with DHPBP. In addition, partially purified DHPBP increased the sedimentation rate of purified alpha-s* but not alpha-i-3*. G proteins were immunoprecipitated with an antibody to the alpha-l subunit of the DHPBP, and, in addition, both alpha-s and the beta-subunit of G(s) were detected in Western blots of the partially purified DHPBP. The results suggest that G(s) and Ca2+ channels are closely associated in the T-tubule plasma membrane, and we conclude that skeletal muscle Ca2+ channels are direct effectors for G(s). C1 BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,DEPT BIOCHEM,HANOVER,NH 03756. NIDDKD,MOLEC PATHOPHYSIOL BRANCH,BETHEDSA,MD 20892. RP HAMILTON, SL (reprint author), BAYLOR COLL MED,DEPT MOLEC PHYSIOL & BIOPHYS,HOUSTON,TX 77030, USA. FU NHLBI NIH HHS [HL37028]; NIAMS NIH HHS [AR38970]; NIDDK NIH HHS [DK19318] NR 48 TC 67 Z9 67 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 15 PY 1991 VL 266 IS 29 BP 19528 EP 19535 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GK667 UT WOS:A1991GK66700061 PM 1655789 ER PT J AU NAKAMURA, H YOSHIMURA, K JAFFE, HA CRYSTAL, RG AF NAKAMURA, H YOSHIMURA, K JAFFE, HA CRYSTAL, RG TI INTERLEUKIN-8 GENE-EXPRESSION IN HUMAN BRONCHIAL EPITHELIAL-CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NEUTROPHIL-ACTIVATING PEPTIDE; CHEMOTACTIC FACTOR; POLYMORPHONUCLEAR LEUKOCYTES; ALPHA-1-PROTEINASE INHIBITOR; MAMMALIAN-CELLS; LYMPHOCYTES-T; MESSENGER-RNA; PROTEIN; RELEASE; LUNG AB The capacity of cells of the human bronchial epithelium to express the gene for interleukin-8 (IL-8) was evaluated in bronchial epithelium derived cell lines, HS-24 and BET-1A, using tumor necrosis factor-alpha (TNF) as a model inflammatory stimulus. As in other epithelium, TNF markedly increased the level of the 1.8-kilobase IL-8 mRNA transcripts in both bronchial epithelial cell lines. In HS-24 cells, nuclear run-on analyses showed the IL-8 gene transcription rate was dramatically increased, more than 30-fold, after TNF stimulation. The half-life of IL-8 mRNA transcripts in these cells was approximately 40 min and did not change after TNF stimulation, suggesting that TNF up-regulated IL-8 gene expression mainly at the transcriptional level. DNase I hypersensitivity site mapping of chromatin DNA in resting HS-24 cells demonstrated two hypersensitivity sites within 400 base pairs (bp) 5' to exon I and one site within exon I. However, after TNF stimulation, the exon I hypersensitivity site disappeared and a new site approximately 120 bp 5' to exon I emerged. Consistent with these observations, transfection studies with HS-24 cells using fusion genes composed of the 5'-flanking sequences of the IL-8 gene and a luciferase reporter gene demonstrated potent promoter activity in a 174-bp segment (-130 to +44 relative to the transcription start site), which also exhibited a response to TNF, while a segment from -112 to +44 showed very low promoter activity and no response to TNF. Thus, human bronchial epithelial cells can express the IL-8 gene, with expression in response to the inflammatory mediator TNF regulated mainly at the transcriptional level, and with elements within the 5'-flanking region of the gene that are directly or indirectly modulated by the TNF signal. C1 NHLBI,PULM BRANCH,BLDG 10,RM 6D03,BETHESDA,MD 20892. NR 63 TC 241 Z9 244 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 15 PY 1991 VL 266 IS 29 BP 19611 EP 19617 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GK667 UT WOS:A1991GK66700071 PM 1918068 ER PT J AU CASASFINET, JR KUMAR, A MORRIS, G WILSON, SH KARPEL, RL AF CASASFINET, JR KUMAR, A MORRIS, G WILSON, SH KARPEL, RL TI SPECTROSCOPIC STUDIES OF THE STRUCTURAL DOMAINS OF MAMMALIAN DNA BETA-POLYMERASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ANTIGENIC DETERMINANTS; PROTEIN CONFORMATION; BINDING; IDENTIFICATION; PREDICTION; SEQUENCE; PEPTIDE; LIGANDS AB The 8- and 31-kDa fragments of beta-polymerase, prepared by controlled proteolysis as described (Kumar, A., Widen, S. G., Williams, K. R., Kedar, P., Karpel, R. L., and Wilson, S. H. (1990) J. Biol. Chem. 265, 2124-2131), constitute domains that are structurally and functionally dissimilar. There is little disruption of secondary structure upon proteolysis of the intact enzyme, as suggested from CD spectra of the fragments. Beta-Polymerase is capable of binding both single- and double-stranded nucleic acids: the 8-kDa fragment binds specifically to single-stranded lattices, whereas the 31-kDa domain displays affinity exclusively for double-stranded polynucleotides. These domains are connected by a highly flexible protease-hypersensitive segment that may allow the coordinate functioning of the two binding activities in the intact protein. Beta-Polymerase binds to poly(ethenoadenylic acid) with higher affinity, similar cooperativity, but lesser salt dependence than the 8-kDa fragment. Under physiological conditions, the intact enzyme displays greater binding free energy for single-stranded polynucleotides than the 8-kDa fragment, suggesting that the latter may carry a truncated binding site. Binding of double-stranded calf thymus DNA brings about a moderate quenching of the Tyr and Trp fluorescence emission of both the 31-kDa fragment and beta-polymerase and induces a 6-nm blue shift in the Trp emission maximum of the intact enzyme, but not in the fragment. This latter result is likely due to a change in the relative orientation of the 8- and 31-kDa domains in the intact protein upon interaction with double-stranded DNA; alternatively, the binding mode of intact protein may differ from that of the fragment. Simultaneous interaction of both domains with polynucleotides most likely does not occur since double-stranded DNA binding to the 31-kDa domain of intact beta-polymerase induces the displacement of single-stranded polynucleotides from the 8-kDa domain. These results are evaluated in light of the role of beta-polymerase in DNA repair. C1 UNIV MARYLAND,DEPT CHEM & BIOCHEM,CATONSVILLE,MD 21228. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 22 TC 67 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 OCT 15 PY 1991 VL 266 IS 29 BP 19618 EP 19625 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GK667 UT WOS:A1991GK66700072 PM 1918069 ER PT J AU GARDLIK, S GASSER, R PHILPOT, RM SERABJITSINGH, CJ AF GARDLIK, S GASSER, R PHILPOT, RM SERABJITSINGH, CJ TI THE MAJOR ALPHA-CLASS GLUTATHIONE S-TRANSFERASES OF RABBIT LUNG AND LIVER - PRIMARY SEQUENCES, EXPRESSION, AND REGULATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SUBUNIT CDNA CLONE; NUCLEOTIDE-SEQUENCE; GEL-ELECTROPHORESIS; RIBONUCLEIC-ACID; SEPARATE GENES; MESSENGER-RNA; YB SUBUNIT; RAT; DNA; YC AB The complete primary structures of two distinct rabbit alpha-class glutathione S-transferase (GST) subunits, rbGST-alpha-I and rbGST-alpha-II, have been derived from cDNA sequences. Clones encoding rbGST-alpha-I were isolated from both hepatic and pulmonary cDNA libraries, whereas clones encoding rbGST-alpha-II were isolated only from the hepatic library. Immunochemical and peptide sequence data confirmed that rbGST-alpha-I corresponds to the 27-kDa alpha-class subunit purified from rabbit lung (Serabjit-Singh, C. J., and Bend, J. R. (1988) Arch. Bioch. Biophys. 267, 184-194). Expression of rbGST-alpha-II in liver but not in lung and expression of rbGST-alpha-I in both liver and lung was substantiated by Northern and immunochemical analyses. rbGST-alpha-I and rbGST-alpha-II are composed of 223 and 221 amino acids, respectively, and are 78% identical in amino acid sequence. Compared to published GST sequences, both proteins are most closely related to the human Ha subunit (> 80% identity). On the basis of sequence comparison and Northern and Southern analyses, we conclude that rbGST-alpha-I and rbGST-alpha-II are products of different genes that are independently regulated. Further, the regulatory elements of the alpha-class GST genes may be significantly different in the rabbit as compared to the rat, as evidenced by the lack of induction by phenobarbital of rabbit hepatic or pulmonary alpha-class GST subunits, enzymatic activity, or mRNA. This tissue- and species-dependent expression of the predominant class of cytosolic GST implies unique functions for each isozyme and may contribute to the differential susceptibility of tissues and animals to toxicants. C1 GLAXO INC,RES INST,DEPT DRUG METAB,5 MOORE DR,RES TRIANGLE PK,NC 27709. NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709. NR 45 TC 21 Z9 23 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 15 PY 1991 VL 266 IS 29 BP 19681 EP 19687 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GK667 UT WOS:A1991GK66700080 PM 1918075 ER PT J AU BRANDES, ME WAKEFIELD, LM WAHL, SM AF BRANDES, ME WAKEFIELD, LM WAHL, SM TI MODULATION OF MONOCYTE TYPE-I TRANSFORMING GROWTH-FACTOR-BETA RECEPTORS BY INFLAMMATORY STIMULI SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-NECROSIS-FACTOR; TGF-BETA; EXPRESSION; MACROPHAGES; BINDING; CELLS AB The regulatory mechanisms which control the wide array of cellular responses to transforming growth factor-beta (TGF-beta) are not understood. This report presents evidence that down-regulation of TGF-beta receptors on human monocytes may be one mechanism by which the effects of TGF-beta are regulated. Treatment of monocytes with interferon-gamma (IFN-gamma) and lipopolysaccharide for 18 h reduced monocyte receptor number (approximately 400/cell) in a dose-dependent fashion by 89 and 78%, respectively, as determined by I-125-TGF-beta binding. Incubation with other cytokines (granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor-1, interleukin-1, tumor necrosis factor-alpha) did not alter the amount of TGF-beta bound. The decrease in I-125-TGF-beta binding could not be attributed to competition for receptor sites by secreted TGF-beta. Instead, the decline in binding was due to a loss of type I TGF-beta receptors, the subtype primarily expressed by monocytes, with no decrease in receptor affinity. Lipopolysaccharide-induced receptor loss was rapid (1-4 h), in contrast to the prolonged (12 h) decline induced by IFN-gamma. Loss of receptors was accompanied by a diminished ability of the cells to respond to TGF-beta with an induction of TNF-alpha mRNA. Thus, this monocyte system is the first example of a heterologous agent causing the down-regulation of TGF-beta receptors with a concomitant decline in a TGF-beta-stimulated function. C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. RP BRANDES, ME (reprint author), NIDR,CELLULAR IMMUNOL SECT,IMMUNOL LAB,BLDG 30,RM 329,BETHESDA,MD 20892, USA. NR 38 TC 63 Z9 63 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 OCT 15 PY 1991 VL 266 IS 29 BP 19697 EP 19703 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GK667 UT WOS:A1991GK66700082 PM 1655792 ER PT J AU LETO, TL GARRETT, MC FUJII, H NUNOI, H AF LETO, TL GARRETT, MC FUJII, H NUNOI, H TI CHARACTERIZATION OF NEUTROPHIL NADPH OXIDASE FACTOR-P47-PHOX AND FACTOR-P67-PHOX FROM RECOMBINANT BACULOVIRUSES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; CELL-FREE SYSTEM; RESPIRATORY BURST OXIDASE; 2 CYTOSOLIC COMPONENTS; BOVINE POLYMORPHONUCLEAR NEUTROPHILS; CYTOCHROME-B; CHROMOSOMAL LOCATION; DIPHENYLENE IODONIUM; GUANINE-NUCLEOTIDES; LIGHT CHAIN AB Superoxide production by phagocytic blood cells involves assembly of an active NADPH oxidase complex from components found both in membrane and cytosolic locations in resting cells. We recently cloned cDNAs encoding two cytosolic components (p47-phox and p67-phox) of the oxidase that are deficient in distinct forms of autosomal recessive chronic granulomatous disease. The precise roles of p47-phox and p67-phox were explored further using purified factors produced in large quantities using recombinant baculoviruses to infect cultured Sf9 insect cells. Neither p47-phox nor p67-phox are thought to represent the flavoprotein components of the oxidase, since neither of the purified recombinant factors contained or bound FAD. Recombinant p47-phox and p67-phox are capable of restoring the deficient cytosol from chronic granulomatous disease patient neutrophils to nearly normal levels in a cell-free reconstitution system. Both p47-phox and p67-phox, used together in the absence of neutrophil cytosol, are incapable of supporting cell free production of superoxide, confirming the involvement of other soluble factor(s) in the assembly of an active oxidase in vitro. C1 NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. RP LETO, TL (reprint author), NIAID,HOST DEF LAB,BLDG 10,RM 11N106,BETHESDA,MD 20892, USA. NR 61 TC 121 Z9 124 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 OCT 15 PY 1991 VL 266 IS 29 BP 19812 EP 19818 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GK667 UT WOS:A1991GK66700098 PM 1918085 ER PT J AU ZHOU, HX SZABO, A AF ZHOU, HX SZABO, A TI COMPARISON BETWEEN MOLECULAR-DYNAMICS SIMULATIONS AND THE SMOLUCHOWSKI THEORY OF REACTIONS IN A HARD-SPHERE LIQUID SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID DIFFUSION-CONTROLLED REACTIONS; MODEL AB Molecular dynamics simulations of the kinetics of a model of the reaction A + B --> B in a dense hard-sphere liquid are compared with the predictions of the Smoluchowski approach to diffusion-influenced reactions. The theory employs the radiation boundary condition at contact with an intrinsic rate constant determined by the low-density collision frequency and the potential of mean force determined by the pair distribution function. Hydrodynamic interactions are ignored and the relative diffusion coefficient is taken as twice the self-diffusion constant. Considering the lack of free parameters and the many-body nature of the problem, the agreement between theory and simulations is surprisingly good over a wide range of B concentrations. Of particular interest is that the above theory provides an exact description of the kinetics at short times. RP ZHOU, HX (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. RI Szabo, Attila/H-3867-2012; Zhou, Huan-Xiang/M-5170-2016 OI Zhou, Huan-Xiang/0000-0001-9020-0302 NR 21 TC 65 Z9 66 U1 0 U2 9 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD OCT 15 PY 1991 VL 95 IS 8 BP 5948 EP 5952 DI 10.1063/1.461616 PG 5 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA GJ592 UT WOS:A1991GJ59200045 ER PT J AU HAMMOND, DL RUDA, MA AF HAMMOND, DL RUDA, MA TI DEVELOPMENTAL ALTERATIONS IN NOCICEPTIVE THRESHOLD, IMMUNOREACTIVE CALCITONIN GENE-RELATED PEPTIDE AND SUBSTANCE-P, AND FLUORIDE-RESISTANT ACID-PHOSPHATASE IN NEONATALLY CAPSAICIN-TREATED RATS SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE PLASTICITY; SPINAL CORD; ANTINOCICEPTION; DORSAL ROOT GANGLION; SPROUTING; PRIMARY AFFERENTS ID PRIMARY SENSORY NEURONS; CENTRAL NERVOUS-SYSTEM; PRIMARY AFFERENT NEURONS; DORSAL-ROOT-GANGLIA; SPINAL-CORD; IMMUNOHISTOCHEMICAL ANALYSIS; THERMAL NOCICEPTION; TRIGEMINAL GANGLION; GELATINOSA ROLANDI; FINE-STRUCTURE AB This study examined the effect of neonatal administration of capsaicin on nociceptive threshold and the distribution of calcitonin gene-related peptide (CGRP), substance P (SP), and fluoride-resistant acid phosphatase (FRAP) in the dorsal horn of the spinal cord during the course of development (10 days to 12 weeks of age) in the rat. As early as 10 days of age, CGRP-like immunoreactivity was reduced in laminae I, II, and V, as well as in the bundles of fibers situated dorsal and ventral to the central canal. However, beginning on or about 6 weeks of age, the density of CGRP-like immunoreactivity in the superficial laminae and in the bundles dorsal and ventral to the central canal increased. Moreover, thick, nonvaricose CGRP-like immunoreactive fibers appeared in laminae III and IV. These recurring fibers were of primary afferent origin as demonstrated by their disappearance after multiple, unilateral rhizotomies. A similar age-dependent alteration in the density of FRAP activity was also observed. Although virtually absent at 10 days of age after neonatal administration of capsaicin, the density of FRAP activity increased in lamina II by 8 weeks of age. This activity disappeared after multiple, unilateral rhizotomies, indicating that the FRAP activity that reappeared was of primary afferent origin. Neonatal administration of capsaicin also reduced the density of SP-like immunoreactivity in the dorsal horn as early as 10 days of age, although the density of SP-like immunoreactivity showed some recovery after 6 weeks of age. However, unlike CGRP-like immunoreactivity or FRAP activity, the density of SP-like immunoreactivity in capsaicin-treated rats was not detectably altered by multiple, unilateral rhizotomies, indicating that it originated principally from intrinsic dorsal horn neurons. Age-dependent alterations in both thermal and mechanical, but not chemical, nociceptive thresholds were also observed in these same animals. Thus, tail flick latency, hot plate latency, and paw withdrawal threshold were maximally increased at 6 weeks of age, after which time thresholds declined to vehicle-treated values. In contrast, capsaicin-treated animals were uniformly insensitive to ophthalmic administration of capsaicin. The correspondence between developmental alterations in CGRP-like immunoreactivity or FRAP activity and in thermal and mechanical nociceptive thresholds is suggestive of a role of CGRP- or FRAP-containing primary afferents in thermal and mechanical nociception. C1 GD SEARLE & CO,DEPT CENT NERVOUS SYST DIS RES,SKOKIE,IL 60077. NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. OI Hammond, Donna/0000-0002-2537-0441 NR 66 TC 85 Z9 85 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 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD OCT 15 PY 1991 VL 312 IS 3 BP 436 EP 450 DI 10.1002/cne.903120310 PG 15 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA GL726 UT WOS:A1991GL72600009 PM 1721077 ER PT J AU SCHNITTMAN, SM SINGER, KH GREENHOUSE, JJ STANLEY, SK WHICHARD, LP HAYNES, BF FAUCI, AS AF SCHNITTMAN, SM SINGER, KH GREENHOUSE, JJ STANLEY, SK WHICHARD, LP HAYNES, BF FAUCI, AS TI THYMIC MICROENVIRONMENT INDUCES HIV EXPRESSION - PHYSIOLOGICAL SECRETION OF IL-6 BY THYMIC EPITHELIAL-CELLS UP-REGULATES VIRUS EXPRESSION IN CHRONICALLY INFECTED-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; IMMUNE-DEFICIENCY SYNDROME; T-CELL; MONOCLONAL-ANTIBODIES; PERIPHERAL-BLOOD; HUMAN THYMOCYTES; BINDING; RETROVIRUS; ACTIVATION; ANTIGEN AB The hallmark of infection with HIV-1 is progressive depletion and qualitative dysfunction of the CD4+ Th cell population in infected individuals. Clinical trials of antiretroviral agents have shown that, despite suppression of virus replication, regeneration of the T cell pool does not occur. One proposed explanation for the defective regenerative capacity of the CD4+ T cell pool is infection of early T lymphocyte progenitors or stem cells. An additional explanation could be failure of cells of the intrathymic microenvironment (thymic epithelial (TE) cells) to carry out critical nurturing functions for developing thymocytes, i.e., secretion of thymocytetrophic cytokines and expression of adhesion molecules. This study examines the effect of HIV on cultured TE cells and determines the role of TE cells in the regulation of viral expression in chronically HIV-infected cells. We found no evidence of infection of TE cells after exposure to HIV-1. However, normal human serum induced secretion of IL-6 by TE cells; induction of TE IL-6 was partially blocked by anti-IFN-gamma antibodies. Moreover, supernatants from TE cells maintained in normal human serum up-regulated HIV replication in chronically HIV-1-infected cells. Because intrathymic T cell precursors can be infected with HIV and T cell precursors come into close contact with TE cells in the thymus, IL-6 secreted by TE cells during normal intrathymic development may induce HIV expression in infected thymocytes in vivo and promote the intrathymic spread of HIV. C1 DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT MICROBIOL IMMUNOL,DURHAM,NC 27710. RP SCHNITTMAN, SM (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM 11B-13,BETHESDA,MD 20892, USA. FU NIAMS NIH HHS [AR34808] NR 41 TC 41 Z9 41 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 1991 VL 147 IS 8 BP 2553 EP 2558 PG 6 WC Immunology SC Immunology GA GK972 UT WOS:A1991GK97200019 PM 1918977 ER PT J AU SKALERIC, U ALLEN, JB SMITH, PD MERGENHAGEN, SE WAHL, SM AF SKALERIC, U ALLEN, JB SMITH, PD MERGENHAGEN, SE WAHL, SM TI INHIBITORS OF REACTIVE OXYGEN INTERMEDIATES SUPPRESS BACTERIAL-CELL WALL-INDUCED ARTHRITIS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR NECROSIS FACTOR; GROWTH FACTOR-BETA; SUPEROXIDE-DISMUTASE; FREE-RADICALS; RHEUMATOID-ARTHRITIS; HYDROGEN-PEROXIDE; PROTEOGLYCAN SYNTHESIS; INDUCED POLYARTHRITIS; ARTICULAR-CARTILAGE; GIARDIA-LAMBLIA AB Peritoneal and peripheral blood monocyte-macrophages from inbred Lewis (LEW) rats generate higher levels of reactive oxygen intermediates (ROI) in response to group A streptococcal cell walls (SCW) than do similar populations of cells from histocompatible Fischer rats. This differential sensitivity of the phagocytes to SCW is reflected in differences in susceptibility of the two strains to the development of arthritis in response to SCW. After systemic administration of the SCW, LEW rats develop acute and chronic erosive polyarthritis, whereas the Fischer rats are arthritis resistant. Inasmuch as these data suggested that the SCW-induced release of inflammatory cell products such as ROI might be an important contributory factor in the pathogenesis of arthritis in the LEW rats, the animals were injected with SCW and treated with ROI inhibitors. A single intraarticular injection of superoxide dismutase or catalase significantly reduced the SCW-induced inflammatory response and evolution of erosive arthritis in the treated animals (articular index 3.6 +/- 0.36 for SCW only vs 1.4 +/- 0.3 for SCW + SOD; p < 0.001; n = 6). These data indicate that ROI play a pivotal role in synovitis and, furthermore, that suppression of these inflammatory mediators modulates both acute and chronic SCW-induced inflammation of the joint. C1 NIDA,IMMUNOL LAB,LEXINGTON,KY 40583. NR 41 TC 38 Z9 38 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 OCT 15 PY 1991 VL 147 IS 8 BP 2559 EP 2564 PG 6 WC Immunology SC Immunology GA GK972 UT WOS:A1991GK97200020 PM 1655894 ER PT J AU BROXMEYER, HE SHERRY, B COOPER, S RUSCETTI, FW WILLIAMS, DE AROSIO, P KWON, BS CERAMI, A AF BROXMEYER, HE SHERRY, B COOPER, S RUSCETTI, FW WILLIAMS, DE AROSIO, P KWON, BS CERAMI, A TI MACROPHAGE INFLAMMATORY PROTEIN (MIP)-1-BETA ABROGATES THE CAPACITY OF MIP-1-ALPHA TO SUPPRESS MYELOID PROGENITOR-CELL GROWTH SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLONY FORMATION INVITRO; GRANULOCYTE-MACROPHAGE; CHEMOKINETIC PROPERTIES; IDENTIFICATION; MURINE; CLONING; EXPRESSION; LIGAND; PROLIFERATION; RECEPTOR AB The effects of recombinant murine macrophage inflammatory protein (MIP)-1-beta and MIP-2 on the suppressive activity of MIP-1-alpha were tested using colony formation by human and murine bone marrow burst-forming unit-erythroid (BFU-E), colony-forming unit-granulocyte erythroid macrophage, megakaryocyte (CFU-GEMM), and colony-forming unitgranulocyte macrophage (CFU-GM) progenitor cells. MIP-1-beta, but not MIP-2, when added with MIP-1-alpha to cells, blocked the suppressive effects of MIP-1-alpha on both human and murine BFU-E, CFU-GEMM, and CFU-GM colony formation. Similar results were observed regardless of the early acting cytokines used: human rGM-CSF plus human rIL-3, and two recently described potent cytokines, a genetically engineered human rGM-CSF/IL-3 fusion protein and MGF, a c-kit ligand. The more potent the stimuli, the greater the suppressive activity noted. Pulse treatment of hu bone marrow cells with MIP-1-alpha at 4-degrees-C for 1 h was as effective in inhibiting colony formation as continuous exposure of cells to MIP-1-alpha, and the pulsing effect with MIP-1-alpha could not be overcome by subsequent exposure of cells to MIP-1-beta. Also, pulse exposure of cells to MIP-1-beta blocked the activity of subsequently added MIP-1-alpha. For specificity, the action of a nonrelated myelosuppressive factor H-ferritin, was compared. MIP-1-alpha and H-ferritin were shown to act on similar target populations of early BFU-E, CFU-GEMM, and CFU-GM. MIP-1-beta did not block the suppressive activity of H-ferritin. Also, hemin and an inactive recombinant human H-ferritin mutein counteracted the suppressive effects of the wildtype H-ferritin molecule, but did not block the suppressive effects of MIP-1-alpha. These results show that MIP-1-beta's ability to block the action of MIP-1-alpha is specific. In addition, the results suggest that MIP-1-alpha and MIP-beta can, through rapid action, modulate early myeloid progenitor cell proliferation. C1 INDIANA UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,DEPT MED HEMATOL ONCOL,INDIANAPOLIS,IN 46202. IMMUNEX CORP,DEPT EXPTL HEMATOL,SEATTLE,WA 98101. ROCKEFELLER UNIV,MED BIOCHEM LAB,NEW YORK,NY 10021. NCI,BIOL RESPONSE MODIFIER PROGRAM,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21701. UNIV MILAN,DEPT SCI & BIOMED TECHNOL,I-20122 MILAN,ITALY. RP BROXMEYER, HE (reprint author), INDIANA UNIV,SCH MED,WALTHER ONCOL CTR,975 W WALNUT ST,IB 501,INDIANAPOLIS,IN 46202, USA. RI arosio, paolo/E-6817-2010 FU NCI NIH HHS [R37 CA36464, R01 CA36740]; NIAID NIH HHS [R01 AI29110] NR 31 TC 92 Z9 92 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 OCT 15 PY 1991 VL 147 IS 8 BP 2586 EP 2594 PG 9 WC Immunology SC Immunology GA GK972 UT WOS:A1991GK97200024 PM 1918979 ER PT J AU LETOURNEUR, O KENNEDY, ICS BRINI, AT ORTALDO, JR OSHEA, JJ KINET, JP AF LETOURNEUR, O KENNEDY, ICS BRINI, AT ORTALDO, JR OSHEA, JJ KINET, JP TI CHARACTERIZATION OF THE FAMILY OF DIMERS ASSOCIATED WITH FC-RECEPTORS (FC-EPSILON-RI AND FC-GAMMA-RIII) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; AFFINITY IGE RECEPTOR; IMMUNOGLOBULIN-E; ZETA-CHAIN; ETA-CHAIN; EXPRESSION; SUBUNIT; COMPLEX; CD16; PALMITOYLATION AB The receptor for IgE (Fc-epsilon-RI) is a multimeric complex containing one alpha-chain, one beta-chain with four transmembrane domains and one homodimer of disulfide-linked gamma-chains. The Fc-epsilon-RI gamma-chains form additional disulfide-linked dimers with the homologous zeta- and eta-chains, as part of the TCR complex. The low affinity receptor for IgG (Fc-gamma-RIII)2 on NK cells is also associated with zeta-chains. Here we show that the gamma-chain is expressed in NK cells both as a group of heterogenous gamma-gamma homodimers and also as a heterodimer bound to zeta. Fc-gamma-RIIIA is associated with three types of dimers zeta-zeta, gamma-zeta, and notably gamma-gamma as well. In fact, gamma-gamma appears to be the predominant species associating with Fc-gamma-RIIIA. The surface expressed Fc-epsilon-RI also associates with the same group of heterogenous gamma-gamma homodimers. We also show that there is no C-terminal posttranslational cleavage of gamma occurring before its insertion into the plasma membrane as previously suggested. Thus, like the TCR, Fc-gamma-RIIIA may form a variety of receptor isoforms, though at present we do not understand the functional implications of these structures. C1 NIAID,MOLEC ALLERGY & IMMUNOL SECT,TWINBROOK 2 BLDG,12441 PARKLAWN DR,ROCKVILLE,MD 20852. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701. NR 28 TC 108 Z9 110 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 1991 VL 147 IS 8 BP 2652 EP 2656 PG 5 WC Immunology SC Immunology GA GK972 UT WOS:A1991GK97200033 PM 1833456 ER PT J AU HOOK, WA BERENSTEIN, EH ZINSSER, FU FISCHLER, C SIRAGANIAN, RP AF HOOK, WA BERENSTEIN, EH ZINSSER, FU FISCHLER, C SIRAGANIAN, RP TI MONOCLONAL-ANTIBODIES TO THE LEUKOCYTE COMMON ANTIGEN (CD45) INHIBIT IGE-MEDIATED HISTAMINE-RELEASE FROM HUMAN BASOPHILS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TYROSINE-PROTEIN-KINASE; HUMAN LYMPHOCYTES-T; LEUKEMIA-CELL LINE; SIGNAL TRANSDUCTION; MAST-CELLS; HIGH-AFFINITY; RECEPTOR; ACTIVATION; PHOSPHORYLATION; PHOSPHATASE AB mAb were selected that inhibited IgE-mediated histamine release from human basophils. The two mAb, HB 9AB6 and HB 10AB2, are of the IgG1 subclass and have a 50% inhibitory concentration of 0.16 to 1.1-mu-g/ml. The mAb required several hours of incubation with the basophils at 37-degrees-C to induce maximum inhibition. Neither mAb directly released histamine from human basophils nor did they inhibit release induced by formylmethionine tripeptide, calcium ionophore A23187, or PMA. There was little inhibition of IgE-mediated release when the cells were preincubated with the mAb at 4-degrees-C. By FACS analysis the 2 mAb bound to all peripheral blood leukocytes and immunoprecipitated a approximately 200-kDa protein from peripheral blood leukocytes and several cell lines of human origin. In binding studies and by sequential immunoprecipitation the 2 mAb and a known anti-CD45 mAb bound to the same protein. However, the mAb recognized different epitopes. Therefore, mAb to the CD45 surface Ag, a membrane protein tyrosine phosphatase, inhibits IgE-receptor mediated histamine release from human basophils. The data suggest a link between protein tyrosine phosphorylation and high affinity IgE receptor-mediated signal transduction in human basophils. RP HOOK, WA (reprint author), NIDR,IMMUNOL LAB,CLIN IMMUNOL SECT,BLDG 10,ROOM 1N106,BETHESDA,MD 20892, USA. NR 64 TC 63 Z9 64 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 OCT 15 PY 1991 VL 147 IS 8 BP 2670 EP 2676 PG 7 WC Immunology SC Immunology GA GK972 UT WOS:A1991GK97200036 PM 1717571 ER PT J AU SHER, A FIORENTINO, D CASPAR, P PEARCE, E MOSMANN, T AF SHER, A FIORENTINO, D CASPAR, P PEARCE, E MOSMANN, T TI PRODUCTION OF IL-10 BY CD4+ LYMPHOCYTES-T CORRELATES WITH DOWN-REGULATION OF TH1 CYTOKINE SYNTHESIS IN HELMINTH INFECTION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL SUBSETS; IMMUNITY AB After the onset of parasite egg deposition, mice infected with the helminth Schistosoma mansoni mount strong Th2 cytokine responses in the absence of significant Th1 cytokine synthesis. To examine the basis of this immunoregulatory state, spleen or lymph node cells from schistosome-infected mice were stimulated with parasite-specific Ag and the supernatants tested for their capacity to suppress IFN-gamma synthesis by a Th1 cell line. Strong inhibition was observed that was neutralized by a mAb against IL-10, a cytokine previously shown to down-regulate Th1 cytokine synthesis. By means of ELISA measurements the production of IL-10 in schistosome infection was confirmed and shown to depend on CD4+ T cells. IL-10 synthesis stimulated by either mitogen or Ag was observed only at those stages of infection when Th2 response induction and Th1 cytokine down-regulation also occurred and was not detected in mice vaccinated with attenuated parasites. Moreover, the addition of the neutralizing anti-IL-10 mAb to Ag-stimulated spleen cell cultures from infected mice caused a dramatic augmentation in IFN-gamma synthesis. These findings suggest that IL-10 is responsible for the down-regulation of Th1 responses observed in schistosome infections, a phenomenon that may enable the parasite to escape potentially harmful cell-mediated responses. C1 DNAX RES INST MOLEC & CELLULAR BIOL INC,PALO ALTO,CA 94304. UNIV ALBERTA,DEPT IMMUNOL,EDMONTON T6G 2G7,ALBERTA,CANADA. RP SHER, A (reprint author), NIAID,PARASIT DIS LAB,IMMUNOL & CELL BIOL SECT,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. OI Fiorentino, David/0000-0001-7951-3674 NR 15 TC 326 Z9 335 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 1991 VL 147 IS 8 BP 2713 EP 2716 PG 4 WC Immunology SC Immunology GA GK972 UT WOS:A1991GK97200042 PM 1680917 ER PT J AU NOMIZU, M UTANI, A SHIRAISHI, N YAMADA, Y ROLLER, PP AF NOMIZU, M UTANI, A SHIRAISHI, N YAMADA, Y ROLLER, PP TI SYNTHESIS OF A DISULFIDE LINKED HETEROTRIMERIC ACTIVE-SITE PEPTIDE SEGMENT OF LAMININ SO JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS LA English DT Article ID CYSTINE-PEPTIDES; GLYCOPROTEIN; CYSTEINE AB A disulphide linked 95-mer heterotrimeric active site segment of laminin (B2 chain Met 1538 replaced with Nle) was synthesized by the solid phase peptide synthesis method utilizing the two-step trimethylsilyl bromide-HF deprotection procedure and the interlinking of the three subunits by the stepwise selective formation of two disulphide bridges using air-oxidation and thallium(III) trifluoroacetate oxidation. C1 NCI,MED CHEM LAB,37,SC-02,BETHESDA,MD 20892. NIDR,DEV BIOL & ANOMALIES LAB,BETHESDA,MD 20892. NR 16 TC 5 Z9 5 U1 0 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK MILTON ROAD, CAMBRIDGE, CAMBS, ENGLAND CB4 4WF SN 0022-4936 J9 J CHEM SOC CHEM COMM JI J. Chem. Soc.-Chem. Commun. PD OCT 15 PY 1991 IS 20 BP 1434 EP 1435 DI 10.1039/c39910001434 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA GM334 UT WOS:A1991GM33400012 ER PT J AU LEIKIN, S RAU, DC PARSEGIAN, VA AF LEIKIN, S RAU, DC PARSEGIAN, VA TI MEASURED ENTROPY AND ENTHALPY OF HYDRATION AS A FUNCTION OF DISTANCE BETWEEN DNA DOUBLE HELICES SO PHYSICAL REVIEW A LA English DT Article ID FORCES AB The temperature sensitivity of hydration forces between Mn2+-DNA helices in ordered arrays has been used to measure the entropic part of the interaction free-energy versus helix separation. This entropy is positive, and like the hydration force itself, grows exponentially as helices move closer. Measured forces show an abrupt transition between regions of interactions with quite different characteristic decay lengths, with a discontinuous change in interhelical spacing. However, both the entropic and enthalpic components of the interaction free-energy maintain smooth single-exponential variation across this transition. C1 AN FRUMKIN ELECTROCHEM INST,MOSCOW,USSR. RP LEIKIN, S (reprint author), NIH,BLDG 10,ROOM 9B07,BETHESDA,MD 20892, USA. RI Leikin, Sergey/A-5518-2008 OI Leikin, Sergey/0000-0001-7095-0739 NR 23 TC 84 Z9 84 U1 0 U2 7 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1050-2947 J9 PHYS REV A JI Phys. Rev. A PD OCT 15 PY 1991 VL 44 IS 8 BP 5272 EP 5278 DI 10.1103/PhysRevA.44.5272 PG 7 WC Optics; Physics, Atomic, Molecular & Chemical SC Optics; Physics GA GM060 UT WOS:A1991GM06000055 ER PT J AU ARMSTRONG, DL ROSSIER, MF SHCHERBATKO, AD WHITE, RE AF ARMSTRONG, DL ROSSIER, MF SHCHERBATKO, AD WHITE, RE TI ENZYMATIC GATING OF VOLTAGE-ACTIVATED CALCIUM CHANNELS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID PROTEIN-KINASE-C; CLONAL PITUITARY-CELLS; MUSCLE TRANSVERSE TUBULES; FREE MEMBRANE PATCHES; GUINEA-PIG HEART; SKELETAL-MUSCLE; VENTRICULAR MYOCYTES; ACTION-POTENTIALS; CHROMAFFIN CELLS; ARACHIDONIC-ACID RP ARMSTRONG, DL (reprint author), NIEHS,CELLULAR & MOLEC PHARMACOL LAB 7-07,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 71 TC 37 Z9 37 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 OCT 14 PY 1991 VL 635 BP 26 EP 34 DI 10.1111/j.1749-6632.1991.tb36478.x PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM206 UT WOS:A1991JM20600004 PM 1660238 ER PT J AU VOGEL, SS DELANEY, K ZIMMERBERG, J AF VOGEL, SS DELANEY, K ZIMMERBERG, J TI THE SEA-URCHIN CORTICAL REACTION - A MODEL SYSTEM FOR STUDYING THE FINAL STEPS OF CALCIUM-TRIGGERED VESICLE FUSION SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID SQUID GIANT SYNAPSE; TRANSMITTER RELEASE; MEMBRANE-FUSION; PLASMA-MEMBRANE; LIPID BILAYERS; EGGS; EXOCYTOSIS; INVITRO; CELLS; ACTIVATION C1 NYU,NEW YORK,NY 10003. AT&T BELL LABS,MURRAY HILL,NJ 07974. RP VOGEL, SS (reprint author), NICHHD,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892, USA. RI Vogel, Steven/A-3585-2012; OI Vogel, Steven/0000-0002-3005-2667 NR 39 TC 26 Z9 26 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 OCT 14 PY 1991 VL 635 BP 35 EP 44 DI 10.1111/j.1749-6632.1991.tb36479.x PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM206 UT WOS:A1991JM20600005 PM 1741591 ER PT J AU ETCHEBERRIGARAY, R FIEDLER, JL POLLARD, HB ROJAS, E AF ETCHEBERRIGARAY, R FIEDLER, JL POLLARD, HB ROJAS, E TI ENDOPLASMIC-RETICULUM AS A SOURCE OF CA-2+ IN NEUROTRANSMITTER SECRETION SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID RAT-BRAIN SYNAPTOSOMES; SARCOPLASMIC-RETICULUM; CALCIUM RELEASE; NERVE-TERMINALS; ATP; ACETYLCHOLINE; IDENTIFICATION; BLOCKADE; CHANNEL; MUSCLE RP ETCHEBERRIGARAY, R (reprint author), NIDDKD, CELL BIOL & GENET LAB, BETHESDA, MD 20892 USA. RI Fiedler, Jenny/I-5617-2016 NR 24 TC 9 Z9 9 U1 0 U2 3 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 OCT 14 PY 1991 VL 635 BP 90 EP 99 DI 10.1111/j.1749-6632.1991.tb36484.x PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM206 UT WOS:A1991JM20600010 PM 1683762 ER PT J AU BLUMENTHAL, R SCHOCH, C PURI, A CLAGUE, MJ AF BLUMENTHAL, R SCHOCH, C PURI, A CLAGUE, MJ TI A DISSECTION OF STEPS LEADING TO VIRAL ENVELOPE PROTEIN-MEDIATED MEMBRANE-FUSION SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID INFLUENZA-VIRUS HEMAGGLUTININ; FLUORESCENCE MICROSCOPY; SURFACE-DENSITY; KINETICS; EVENTS; GLYCOPROTEIN; FIBROBLASTS; CELLS; DELAY; FLOW RP BLUMENTHAL, R (reprint author), NCI,LMMB,MEMBRANE STRUCT & FUNCT SECT,BLDG 10,RM 4B56,BETHESDA,MD 20892, USA. OI Clague, Michael/0000-0003-3355-9479 NR 22 TC 44 Z9 44 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 OCT 14 PY 1991 VL 635 BP 285 EP 296 DI 10.1111/j.1749-6632.1991.tb36499.x PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM206 UT WOS:A1991JM20600025 PM 1741588 ER PT J AU ZIMMERBERG, J CURRAN, M COHEN, FS AF ZIMMERBERG, J CURRAN, M COHEN, FS TI A LIPID PROTEIN COMPLEX HYPOTHESIS FOR EXOCYTOTIC FUSION PORE FORMATION SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID INTEGRAL MEMBRANE-PROTEIN; ADRENAL CHROMAFFIN CELLS; SQUID GIANT SYNAPSE; INFLUENZA HEMAGGLUTININ; MAST-CELLS; PHOSPHOLIPID-BILAYERS; TRANSMITTER RELEASE; SECRETORY VESICLE; HYDRATION FORCES; EVENTS C1 NICHHD,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892. RUSH MED COLL,DEPT PHYSIOL,CHICAGO,IL 60612. FU NIGMS NIH HHS [GM 27367] NR 51 TC 52 Z9 52 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 OCT 14 PY 1991 VL 635 BP 307 EP 317 DI 10.1111/j.1749-6632.1991.tb36501.x PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM206 UT WOS:A1991JM20600027 PM 1741589 ER PT J AU POLLARD, HB ROJAS, E PASTOR, RW ROJAS, EM GUY, HR BURNS, AL AF POLLARD, HB ROJAS, E PASTOR, RW ROJAS, EM GUY, HR BURNS, AL TI SYNEXIN - MOLECULAR MECHANISM OF CALCIUM-DEPENDENT MEMBRANE-FUSION AND VOLTAGE-DEPENDENT CALCIUM-CHANNEL ACTIVITY - EVIDENCE IN SUPPORT OF THE HYDROPHOBIC BRIDGE HYPOTHESIS FOR EXOCYTOTIC MEMBRANE-FUSION SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID PHOSPHOLIPID-BILAYER MEMBRANES; NUCLEAR MAGNETIC-RESONANCE; SPIN-LATTICE RELAXATION; F-ACTIN INTERACTIONS; CHROMAFFIN GRANULE; BIOLOGICAL-MEMBRANES; DYNAMICS SIMULATION; MODEL MEMBRANES; H-2 NMR; VESICLES C1 US FDA,CTR BIOL EVALUAT & RES,BIOPHYS LAB,BETHESDA,MD 20892. NCI,MATH BIOL LAB,BETHESDA,MD 20892. RP POLLARD, HB (reprint author), NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892, USA. NR 60 TC 33 Z9 33 U1 1 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 OCT 14 PY 1991 VL 635 BP 328 EP 351 DI 10.1111/j.1749-6632.1991.tb36503.x PG 24 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM206 UT WOS:A1991JM20600029 PM 1660240 ER PT J AU CHIUE, CC HUANG, SJ AF CHIUE, CC HUANG, SJ TI MPP+ ENHANCES POTASSIUM-EVOKED STRIATAL DOPAMINE RELEASE THROUGH A OMEGA-CONOTOXIN-INSENSITIVE, TETRODOTOXIN-SENSITIVE AND NIMODIPINE-SENSITIVE CALCIUM-DEPENDENT MECHANISM SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID CHANNELS; DIHYDROPYRIDINE; INVIVO RP CHIUE, CC (reprint author), NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892, USA. NR 14 TC 18 Z9 18 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 OCT 14 PY 1991 VL 635 BP 393 EP 396 DI 10.1111/j.1749-6632.1991.tb36507.x PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM206 UT WOS:A1991JM20600033 PM 1741592 ER PT J AU BURNS, AL MAGENDZO, K SRIVASTAVA, M ROJAS, E CULTRARO, C DELAFUENTE, M HELDMAN, J PARRA, C POLLARD, HB AF BURNS, AL MAGENDZO, K SRIVASTAVA, M ROJAS, E CULTRARO, C DELAFUENTE, M HELDMAN, J PARRA, C POLLARD, HB TI PROPERTIES AND MODIFICATION OF RECOMBINANT HUMAN SYNEXIN (ANNEXIN VII) SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID MEMBRANE-FUSION; CHROMAFFIN GRANULES; CALCIUM; CHANNELS; PROTEIN; BILAYER C1 US FDA,DIV CARDIORENAL,BETHESDA,MD 20892. RP BURNS, AL (reprint author), NIDDKD,CELL BIOL & GENET LAB,BLDG 8,ROOM 403,BETHESDA,MD 20892, USA. NR 12 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 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD OCT 14 PY 1991 VL 635 BP 450 EP 451 DI 10.1111/j.1749-6632.1991.tb36524.x PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM206 UT WOS:A1991JM20600050 PM 1660250 ER PT J AU KUIJPERS, GAJ LEE, G POLLARD, HB AF KUIJPERS, GAJ LEE, G POLLARD, HB TI IMMUNOELECTRON MICROSCOPY OF THE CALCIUM-BINDING PROTEIN SYNEXIN IN ISOLATED ADRENAL CHROMAFFIN GRANULES AND CHROMAFFIN CELLS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID PURIFICATION RP KUIJPERS, GAJ (reprint author), NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892, USA. NR 5 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 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD OCT 14 PY 1991 VL 635 BP 471 EP 474 DI 10.1111/j.1749-6632.1991.tb36530.x PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM206 UT WOS:A1991JM20600056 PM 1835828 ER PT J AU LEE, G DELAFUENTE, M POLLARD, HB AF LEE, G DELAFUENTE, M POLLARD, HB TI A BARIUM-DEPENDENT CHROMAFFIN GRANULE AGGREGATING PROTEIN FROM BOVINE ADRENAL-MEDULLA AND OTHER TISSUES SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID CALCIUM CHANNELS; MEMBRANE-FUSION; CELLS RP LEE, G (reprint author), NIDDKD,CELL BIOL & GENET,BETHESDA,MD 20892, USA. NR 8 TC 1 Z9 1 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 OCT 14 PY 1991 VL 635 BP 477 EP 479 DI 10.1111/j.1749-6632.1991.tb36532.x PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM206 UT WOS:A1991JM20600058 PM 1741603 ER PT J AU MAGENDZO, K SHIRVAN, A POLLARD, HB BURNS, AL AF MAGENDZO, K SHIRVAN, A POLLARD, HB BURNS, AL TI TISSUE-REGULATED ALTERNATIVE SPLICING OF SYNEXIN MESSENGER-RNA SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID CALCIUM RP MAGENDZO, K (reprint author), NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892, USA. NR 4 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 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD OCT 14 PY 1991 VL 635 BP 483 EP 484 DI 10.1111/j.1749-6632.1991.tb36534.x PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM206 UT WOS:A1991JM20600060 PM 1835829 ER PT J AU LARUELLE, M SIDHU, A CASANOVA, MF WEINBERGER, DR KLEINMAN, JE AF LARUELLE, M SIDHU, A CASANOVA, MF WEINBERGER, DR KLEINMAN, JE TI CHARACTERIZATION OF [I-125] SCH-23982 BINDING IN HUMAN BRAIN - COMPARISON WITH [H-3] SCH-23390 SO NEUROSCIENCE LETTERS LA English DT Article DE [I-125]SCH-23982; [H-3]SCH-23390; D1-DOPAMINE RECEPTOR; RECEPTOR BINDING; HUMAN BRAIN; SPECT IMAGING ID D-1 DOPAMINE RECEPTOR; GUANINE-NUCLEOTIDE REGULATION; AGONIST-BINDING; RAT STRIATUM; LIGAND; CORTEX AB We studied binding of [I-125]SCH 23982 in two regions of human brain, the caudate and the dorsolateral prefrontal cortex. Binding characteristics of [I-125]SCH 23982 and of the non-iodinated tritiated analogue, [H-3]SCH 23390, were compared. In caudate, binding of [I-125]SCH 23982 was consistent with binding to D1 dopamine receptors while in frontal cortex, [I-125]SCH 23982 bound mostly to serotonergic 5HT2 receptors. In contrast to [H-3]SCH 23390, no evidence of binding of [I-125]SCH 23982 to D1 receptors could be found in human frontal cortex. This indicates that iodination of SCH 23390 induces a decrease in its relative D1 versus 5HT2 selectivity that prohibits the use of [I-125]SCH 23982 to label D1 receptors in human cortex. C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,INST RES PSYCHIAT,CLIN BRAIN DISORDER BRANCH,WASHINGTON,DC 20032. NR 16 TC 7 Z9 7 U1 0 U2 1 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 OCT 14 PY 1991 VL 131 IS 2 BP 273 EP 276 DI 10.1016/0304-3940(91)90631-3 PG 4 WC Neurosciences SC Neurosciences & Neurology GA GN084 UT WOS:A1991GN08400034 PM 1837073 ER PT J AU YOSHIMURA, K NAKAMURA, H TRAPNELL, BC CHU, CS DALEMANS, W PAVIRANI, A LECOCQ, JP CRYSTAL, RG AF YOSHIMURA, K NAKAMURA, H TRAPNELL, BC CHU, CS DALEMANS, W PAVIRANI, A LECOCQ, JP CRYSTAL, RG TI EXPRESSION OF THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR GENE IN CELLS OF NONEPITHELIAL ORIGIN SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DEPENDENT PROTEIN-KINASE; NEUTROPHIL ELASTASE GENE; CHLORIDE CHANNELS; AIRWAY EPITHELIA; IDENTIFICATION; CAMP; DNA; LYMPHOCYTES; MUTATIONS; TRANSCRIPTION AB Consistent with the fact that the clinical disorder cystic fibrosis (CF) is manifested on epithelial surfaces, active transcription of the CF transmembrane conductance regulator (CFTR) gene and CFTR mRNA transcripts are detectable in a variety of epithelial cells, suggesting CFTR gene expression might be epithelial cell-specific. However, analysis of the CFTR gene promoter suggests it is a housekeeping gene, implying more widespread expression than only in epithelial cells. To evaluate the latter hypothesis, various human cells of non-epithelial origin, including lung fibroblasts, U-937 histiocytic lymphoma cells, K-562 erythroleukemia cells, HL-60 promyelocytic leukemia cells as well as freshly isolated blood lymphocytes, neutrophils, monocytes, and alveolar macrophages were examined for CFTR gene expression. Although Northern analysis failed to show CFTR mRNA transcripts in these cells, amplification of mRNA (after conversion to cDNA) by polymerase chain reaction combined with Southern analysis demonstrated the presence of CFTR mRNA transcripts at low levels in all cells evaluated except HL-60 cells. Comparative quantitative analysis showed fibroblasts contained 200 - 400 fold less CFTR mRNA transcripts than the T84 and HT-29 colon carcinoma epithelial cell lines, but had similar levels of CFTR transcripts to those of other epithelial cell lines. Nuclear transcription run-on analyses demonstrated very low level CFTR gene transcription in fibroblasts and U-937 cells, similar to that of other epithelial cells, but lower than the T84 and HT-29 colon carcinoma cell lines. Interestingly, while chromatin DNA of fibroblasts had no DNase I hypersensitivity sites in the 5' flanking region of the CFTR gene, HT-29 chromatin DNA exhibited four DNase I accessible sites in the same region, suggesting that these sites may be related to more active transcription of the CFTR gene in the intestinal epithelial cells than in fibroblasts. C1 TRANSGENE SA,F-67082 STRASBOURG,FRANCE. RP YOSHIMURA, K (reprint author), NHLBI,PULM BRANCH,BETHESDA,MD 20892, USA. NR 57 TC 108 Z9 108 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 OCT 11 PY 1991 VL 19 IS 19 BP 5417 EP 5423 DI 10.1093/nar/19.19.5417 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GK752 UT WOS:A1991GK75200044 PM 1717947 ER PT J AU KHOURI, RK KOUDSI, B REDDI, H AF KHOURI, RK KOUDSI, B REDDI, H TI TISSUE TRANSFORMATION INTO BONE INVIVO - A POTENTIAL PRACTICAL APPLICATION SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID BIOLOGICAL PRINCIPLE; INDUCED OSTEOGENESIS; INDUCTIVE PROTEIN; RECONSTRUCTION; DIFFERENTIATION; DEFECTS; GRAFTS; REPAIR; RATS AB The transformation of mesenchymal tissue, such as muscle, into cartilage and bone can be induced by the recently purified osteoinductive factor, osteogenin, and by its parent substratum, demineralized bone matrix. We investigated the possibility of transforming readily available muscle flaps into vascularized bone grafts of various shapes that could be used as skeletal replacement parts. In a rat experimental model, thigh adductor muscle island flaps were placed inside bivalved silicone rubber molds. Prior to closure of the mold, 18 flaps were injected with osteogenin and coated with demineralized bone matrix. Five flaps served as controls and were injected with the vehicle only, and not coated with demineralized bone matrix. The molds were implanted subcutaneously in the rats' flanks and reopened 10 days later. The control flaps consisted of intact muscle without any evidence of tissue transformation, whereas the flaps treated with osteogenin and demineralized bone matrix were entirely transformed into cancellous bone that matched the exact shape of the mold. Using tissue transformation, we were able to generate in vivo, autogenous, well-perfused bones in the shapes of femoral heads and mandibles. C1 NIDR,BONE CELL BIOL SECT,BETHESDA,MD 20892. WASHINGTON UNIV,SCH MED,PLAST SURG RES LAB,ST LOUIS,MO 63110. RP KHOURI, RK (reprint author), WASHINGTON UNIV,SCH MED,DEPT SURG,DIV PLAST SURG,ONE BARNES HOSP PLAZA,SUITE 17424,ST LOUIS,MO 63110, USA. FU PHS HHS [22-3335 44901A] NR 32 TC 131 Z9 133 U1 0 U2 3 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 OCT 9 PY 1991 VL 266 IS 14 BP 1953 EP 1955 DI 10.1001/jama.266.14.1953 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA GH406 UT WOS:A1991GH40600020 PM 1895472 ER PT J AU WLADKOWSKI, BD SMITH, RH MICHEJDA, CJ AF WLADKOWSKI, BD SMITH, RH MICHEJDA, CJ TI THEORETICAL INVESTIGATION OF THE PROTON-INDUCED DECOMPOSITION OF 4,5-DIHYDRO-1,2,3-TRIAZOLE TO FORM THE AZIRIDINIUM ION - INSTABILITY OF THE (2-AMINOETHYL)DIAZONIUM ION SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID 1,3-DIALKYLTRIAZENES; MUTAGENICITY; PRODUCTS; ABINITIO; TRIAZENE; ENERGY AB Ab initio molecular orbital calculations within the Hartree-Fock approximation were used to investigate 4,5-dihydro-1,2,3-triazole (1,2,3-triazoline) and related compounds. Moller-Plesset perturbation theory was used to investigate the effects of electron correlation on the energy of some configurations. The proton affinities for the various protonation sites of 1,2,3-triazoline were obtained. The order of preference for protonation was found to be N3 > N1 >> N2. No local minima were found in the region of the N1-protonated 1,2,3-triazoline at the 3-21G basis set level. Instead the molecule dissociated by an N1-N2 heterolysis pathway. This finding prompted additional investigation of the decomposition process and its intermediates, ultimately leading to the global minimum for this pathway. Searches along the partial potential energy hypersurface for the reaction reveal that certain rotational conformers of the (2-aminoethyl)diazonium ion, the product of the heterolysis, were stable intermediates (the number of intermediates found depended on the basis set used). The diazonium ion in the antiperiplanar conformation was not stable and collapsed to the aziridinium ion with the expulsion of molecular nitrogen. Similar calculations were performed on the neutral and N1-protonated forms of 1-methyl-4,5-dihydro-1,2,3-triazole (1-methyltriazoline) and 1,4,5,6-tetrahydro-1,2,3-triazine (triazinine). These molecules also decomposed upon protonation. The instability of the (2-aminoethyl)diazonium ion led to an investigation of several other substituted diazonium ions including the (2-chloroethyl)diazonium ion, the (2-hydroxyethyl)diazonium ion and the (2-sulfhydrylethyl)diazonium ion. All were found to converge to stable structures in the antiperiplanar conformation. C1 NCI,FREDERICK CANC RES & DEV CTR,MOLEC ASPECTS DRUG DESIGN SECT,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 22 TC 18 Z9 18 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD OCT 9 PY 1991 VL 113 IS 21 BP 7893 EP 7897 DI 10.1021/ja00021a011 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA GJ647 UT WOS:A1991GJ64700011 ER PT J AU REMETA, DP MUDD, CP BERGER, RL BRESLAUER, KJ AF REMETA, DP MUDD, CP BERGER, RL BRESLAUER, KJ TI THERMODYNAMIC CHARACTERIZATION OF DAUNOMYCIN DNA INTERACTIONS - MICROCALORIMETRIC MEASUREMENTS OF DAUNOMYCIN DNA-BINDING ENTHALPIES SO BIOCHEMISTRY LA English DT Article ID STOPPED-FLOW MICROCALORIMETER; SELF-ASSOCIATION; DEOXYRIBONUCLEIC-ACID; MOLECULAR-STRUCTURE; NUCLEIC-ACIDS; DAUNORUBICIN; COMPLEX; D(CPGPTPAPCPG); CONFORMATION; RESOLUTION AB We report the first direct determination of binding enthalpies for the complexation of monomeric daunomycin with a series of 10 polymeric DNA duplexes. These measurements were accomplished by using a recently developed stopped-flow microcalorimeter capable of detecting reaction heats on the microjoule level. This enhanced sensitivity allowed us to measure daunomycin-DNA binding enthalpies at monomeric drug concentrations (e.g., 10-20-mu-M), thereby precluding the need to correct for daunomycin self-association, as has been required in previous batch calorimetric studies [Remeta, D. P., Marky, L. A., & Breslauer, K. J. (1984) Abstracts of Pittsburgh Conference and Exposition on Analytical Chemistry and Applied Spectroscopy, 838a; Breslauer, K. J., Remeta, D. P., Chou, W. Y., Ferrante, R., Curry, J., Zaunczkowski, D., Snyder, J. G., & Marky, L. A. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 8922-8926]. We correct the published daunomycin-DNA binding enthalpies measured by batch calorimetry at higher drug concentrations (e.g., 0.5-1.0 M) for the enthalpy contribution associated with the binding-induced disruption of drug aggregates. The requisite correction term was obtained from a van't Hoff analysis of temperature-dependent NMR measurements on daunomycin solutions. We find remarkable agreement between the net binding enthalpies derived from these corrected batch calorimetric data and the corresponding binding enthalpies measured directly by stopped-flow microcalorimetry. The enhanced sensitivity of the stopped-flow instrument also allowed us to evaluate the influence of drug binding density on the daunomycin-DNA binding enthalpies. This assessment was accomplished by conducting stopped-flow calorimetric measurements over a range of seven different drug-to-phosphate ratios (r). For most of the 10 DNA host duplexes studied, we find that the daunomycin binding enthalpies exhibit small but significant r dependencies. The sensitivity of the stopped-flow instrument also enabled us to detect significant dilution enthalpies for several of the drug-free DNA duplexes, a quantity generally assumed to be negligible in previous studies. We discuss the binding enthalpies, their dependence on binding density, and the duplex dilution enthalpies in terms of the influence of base composition, sequence, conformation/hydration, and binding cooperativity on the sign and the magnitudes of the daunomycin-DNA binding enthalpy data reported here. C1 RUTGERS STATE UNIV,DEPT CHEM,NEW BRUNSWICK,NJ 08903. NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM34469] NR 57 TC 34 Z9 35 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 8 PY 1991 VL 30 IS 40 BP 9799 EP 9809 DI 10.1021/bi00104a032 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GJ473 UT WOS:A1991GJ47300032 PM 1911765 ER PT J AU YEH, CK CHINCHETRU, MA KOUSVELARI, E AF YEH, CK CHINCHETRU, MA KOUSVELARI, E TI CHARACTERISTICS OF C-FOS AND JUN B-GENE EXPRESSION IN A5 CELLS AFTER BETA-ADRENOCEPTOR STIMULATION AND DURING THE CELL-CYCLE SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE PROTOONCOGENE; ISOPROTERENOL; 8-BRCAMP; SALIVARY EPITHELIAL CELL CYCLE ID PROTO-ONCOGENE FOS; RESPONSIVE ELEMENT; MOUSE FIBROBLASTS; AUTO-REGULATION; GROWTH-FACTORS; DNA; TRANSCRIPTION; INDUCTION; RAT; INTERACTS AB The beta-adrenoreceptor agonist isoproterenol elevates cAMP concentrations in the A5 rat salivary epithelial cell line and rapidly and transiently induces the expression of c-fos and jun B at 30 and 60 min following continuous stimulation of these cells. The induction of both genes is mediated by cAMP. We show here that the inducibility of these genes by isoproterenol or 8-BrcAMP is transcriptionally regulated and short (5 min) incubations of A5 cells with either agent is sufficient to trigger the induction of c-fos and jun B. We also have investigated the expression and inducibility of these genes during the A5 cell cycle. Both c-fos and jun B mRNA are elevated at the early phase of the cell cycle and are detectable throughout the cycle. At different stages of the cell cycle in synchronous A5 cells, both genes are as highly induced by isoproterenol or 8-BrcAMP as in asynchronous A5 cells. These studies provide the first evidence for the transcriptional regulation of c-fos and jun B by beta-adrenergic receptor stimulation or cAMP in an epithelial cell line (A5) and demonstrate the coordinate expression and inducibility of these genes at the different stages of the A5 cell cycle. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BLDG 10,ROOM 1A-19,BETHESDA,MD 20892. NR 31 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD OCT 8 PY 1991 VL 1090 IS 2 BP 173 EP 180 DI 10.1016/0167-4781(91)90098-7 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GM738 UT WOS:A1991GM73800004 PM 1681906 ER PT J AU MASIBAY, AS DAMEWOOD, GP BOEGGEMAN, E QASBA, PK AF MASIBAY, AS DAMEWOOD, GP BOEGGEMAN, E QASBA, PK TI EXPRESSION OF BETA-1,4-GALACTOSYLTRANSFERASE GENE DURING 3T3 CELL-GROWTH SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE GLYCOSYLTRANSFERASE; PROLIFERATION ID SURFACE GALACTOSYLTRANSFERASE; 4-BETA-GALACTOSYLTRANSFERASE; CYCLE; LOCALIZATION; GALACTOSYL; RECEPTORS; ADHESION; INVITRO AB The beta-1,4-galactosyltransferase (GT; EC 2.4.1.90) is localized in the trans-cisternae of the Golgi apparatus where it catalyzes the transfer of galactose from UDP-galactose to the N-acetylglucosamine residue of secretory and membrane-bound glycoproteins. Given the potential role of GT in cell-cell interaction and the fact that numerous cell surface events occur during cell growth we studied the possible relationship between GT expression and 3T3 cell growth. The level of GT mRNA increases 3-4-fold 2 h after serum-stimulation of quiescent 3T3 cells. Protein biosynthesis inhibitors like cycloheximide and anisomycin superinduce GT mRNA expression. Concomitant with this increase is an observed rise in the level of GT protein as well as an increase in overall GT enzymatic activity. Antibody-binding studies and direct enzyme assays of intact cells, along with subcellular fractionation experiments indicate that there is an increase in both Golgi and cell surface-associated GT pools upon serum-stimulation of resting cells. We conclude that GT is a member of the cell-cycle dependent genes whose expression is growth regulated. RP MASIBAY, AS (reprint author), NCI,CTR DIAGNOSIS,DIV CANC BIOL,MATH BIOL LAB,BETHESDA,MD 20892, USA. NR 34 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD OCT 8 PY 1991 VL 1090 IS 2 BP 230 EP 234 DI 10.1016/0167-4781(91)90106-V PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GM738 UT WOS:A1991GM73800012 PM 1932115 ER PT J AU LEEHUANG, S KUNG, HF HUANG, PL HUANG, PL LI, BQ HUANG, P HUANG, HI CHEN, HC AF LEEHUANG, S KUNG, HF HUANG, PL HUANG, PL LI, BQ HUANG, P HUANG, HI CHEN, HC TI A NEW CLASS OF ANTI-HIV AGENTS - GAP-31, DAP-30 AND DAP-32 SO FEBS LETTERS LA English DT Article DE AIDS; ANTIVIRAL AGENT; PLANT PROTEIN; N-TERMINAL SEQUENCE ID RIBOSOME-INACTIVATING PROTEIN; DNA TOPOISOMERASE-II; EUKARYOTIC RIBOSOMES; NUCLEOTIDE-SEQUENCE; ALPHA-TRICHOSANTHIN; A-CHAIN; INHIBITOR; RNA; REPLICATION; MECHANISM AB Three inhibitors of human immunodeficiency virus (HIV) have been isolated and purified to homogeneity from Euphorbiaceae himalaya seeds (Gelonium multiflorum) and carnation leaves (Dianthus caryophyllus). These proteins, GAP 31 (Gelonium Anti-HIV Protein 31 kDa) and DAPs 30 and 32 (dianthus anti-HIV proteins, 30 and 32 kDa), inhibit HIV-1 infection and replication in a dose-dependent manner with little toxicity to target cells. The therapeutic indices of these compounds are in the order 10(4), suggesting that they may be clinically important agents in the treatment of AIDS. The N-terminal amino acid sequences of these proteins show little homology to those of previously described anti-HIV proteins. The structure-function features of these HIV inhibitors, based on the 40-60 amino acid residues of N-terminal sequences, are examined. C1 NCI,FREDERICK CANC RES FACIL,BIOCHEM PHYSIOL LAB,FREDERICK,MD 21701. AMER BIOSCI,NEW YORK,NY 10021. NCI,FREDERICK CANC RES FACIL,PROGRAM RESOURCES INC,BIOL CARCINOGEN DEV PROGRAM,FREDERICK,MD 21701. NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. RP LEEHUANG, S (reprint author), NYU,SCH MED,DEPT BIOCHEM,NEW YORK,NY 10016, USA. NR 20 TC 59 Z9 65 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD OCT 7 PY 1991 VL 291 IS 1 BP 139 EP 144 DI 10.1016/0014-5793(91)81122-O PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA GL300 UT WOS:A1991GL30000034 PM 1936243 ER PT J AU RAMPINO, NJ CHRAMBACH, A AF RAMPINO, NJ CHRAMBACH, A TI CONFORMATIONAL CORRELATIVES OF DNA BAND COMPRESSION AND BIDIRECTIONAL MIGRATION DURING FIELD INVERSION GEL-ELECTROPHORESIS, DETECTED BY QUANTITATIVE VIDEO EPIFLUORESCENCE MICROSCOPY SO BIOPOLYMERS LA English DT Article ID SEPARATIONS; MOLECULES; MOBILITY AB Individual DNA molecules in the Mb size range were monitored by epifluorescence video microscopy during field inversion gel electrophoresis (FIGE). DNA migrating in an agarose gel gives rise to characteristic V-conformational elements and when doing so exhibits a reduced mobility. When the V-conformational elements per DNA molecule are few, the degree of retardation appears proportional to the number of V's, and since larger DNA species exhibit more V's, to DNA size. For a particular pulse frequency, the proportionality breaks down progressively as the number of V-conformational elements per DNA molecule increases. The loss of proportionality between DNA length and migration rate is being correlated with the macroscopically observed loss of electrophoretic size discrimination known as band compression. For a particular pulsing frequency and size class of DNA, the loss of size discrimination is thought to be due to the different orientations of migration, caused by the asymmetric distribution of V-conformational elements when the number of these elements is moderate. Small and very large DNA by contrast migrate with the direction of the biased field. These events, analyzed by microscopic measurement, are consistent with the known macroscopically observed double-valued mobilities in FIGE. RP RAMPINO, NJ (reprint author), NICHHD,THEORET & PHYS BIOL LAB,MACROMOLEC ANAL SECT,BETHESDA,MD 20892, USA. NR 13 TC 24 Z9 24 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD OCT 5 PY 1991 VL 31 IS 11 BP 1297 EP 1307 DI 10.1002/bip.360311108 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GW243 UT WOS:A1991GW24300007 PM 1777581 ER PT J AU MCBRIDE, AA ROMANCZUK, H HOWLEY, PM AF MCBRIDE, AA ROMANCZUK, H HOWLEY, PM TI THE PAPILLOMAVIRUS-E2 REGULATORY PROTEINS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID OPEN READING FRAME; EARLY REGION TRANSFORMATION; DNA RECOGNITION SEQUENCE; CARBOXY-TERMINAL DOMAIN; E2 TRANS-ACTIVATOR; TRANSCRIPTIONAL REGULATION; MUTATIONAL ANALYSIS; GENE-PRODUCT; SACCHAROMYCES-CEREVISIAE; CONSTITUTIVE ENHANCER RP MCBRIDE, AA (reprint author), NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892, USA. OI McBride, Alison/0000-0001-5607-5157 NR 71 TC 233 Z9 238 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 5 PY 1991 VL 266 IS 28 BP 18411 EP 18414 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GJ472 UT WOS:A1991GJ47200001 PM 1655748 ER PT J AU HAYDEN, PJ ICHIMURA, T MCCANN, DJ POHL, LR STEVENS, JL AF HAYDEN, PJ ICHIMURA, T MCCANN, DJ POHL, LR STEVENS, JL TI DETECTION OF CYSTEINE CONJUGATE METABOLITE ADDUCT FORMATION WITH SPECIFIC MITOCHONDRIAL PROTEINS USING ANTIBODIES RAISED AGAINST HALOTHANE METABOLITE ADDUCTS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID GLUTAMINE TRANSAMINASE-K; RAT-KIDNEY CYTOSOL; BETA-LYASE; S-CONJUGATE; TOXICITY; NEPHROTOXICITY; MECHANISM; BIOACTIVATION; HEPATITIS; LOCALIZATION AB Antibodies raised against halothane metabolite adducts cross-react with S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC) and S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine metabolite adducts. Using these antibodies in immunohistochemical experiments, metabolite binding was localized to the damaged areas of the proximal tubule after treatment of male rats with TFEC. Immunoblot analysis of subcellular fractions of rat kidney tissue after in vivo treatment with TFEC revealed a high specificity for binding of metabolites to proteins of the mitochondrial fraction. These proteins may represent target molecules which play a role in cysteine conjugate induced nephrotoxicity. C1 W ALTON JONES CELL SCI CTR,LAKE PLACID,NY 12946. NHLBI,CHEM PHARMACOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA38579]; NIDDK NIH HHS [DK38925] NR 39 TC 51 Z9 53 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 OCT 5 PY 1991 VL 266 IS 28 BP 18415 EP 18418 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GJ472 UT WOS:A1991GJ47200002 PM 1917965 ER PT J AU ELY, JA AMBROZ, C BAUKAL, AJ CHRISTENSEN, SB BALLA, T CATT, KJ AF ELY, JA AMBROZ, C BAUKAL, AJ CHRISTENSEN, SB BALLA, T CATT, KJ TI RELATIONSHIP BETWEEN AGONIST-SENSITIVE AND THAPSIGARGIN-SENSITIVE CALCIUM POOLS IN ADRENAL GLOMERULOSA CELLS - THAPSIGARGIN-INDUCED CA2+ MOBILIZATION AND ENTRY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; ENDOPLASMIC-RETICULUM; INTRACELLULAR CALCIUM; PLASMA-MEMBRANE; TUMOR PROMOTER; ACINAR-CELLS; FREE CA-2+; RELEASE; CA-2+-ATPASE; PHOSPHATES AB The relationships between agonist-sensitive calcium pools and those discharged by the Ca2+-ATPase inhibitor thapsigargin were studied in intact bovine adrenal glomerulosa cells and a subcellular adrenocortical membrane fraction. In Fura-2-loaded glomerulosa cells, angiotensin II (AII) stimulated a rapid increase in cytoplasmic Ca2+ concentration ([Ca2+]i) followed by a smaller plateau phase that was dependent on extracellular Ca2+. In such cells thapsigargin caused a sustained and dose-dependent increase in [Ca2+]i which was diminished in Ca2+-deficient medium. The contribution of an influx component to the thapsigargin-induced [Ca2+]i response was demonstrated by measurement of Ca-45 influx rate in glomerulosa cells. Thapsigargin-induced Ca2+ entry was significantly less than that evoked by AII, and its kinetics were similar to those of the concomitant increase in [Ca2+]i. The rate of emptying of the agonist-responsive Ca2+ pool after thapsigargin treatment, as indicated by the progressive decrease in the size of the AII-induced Ca2+ transient, showed a rapid initial (t1/2 = 1.7 min) component that accounted for about 80% of the response and a slowly decreasing phase with t1/2 = 112 min. The latter thapsigargin-resistant component was abolished by the removal of extracellular Ca2+. Pretreatment with AII dose-dependently attenuated but did not abolish the subsequent Ca2+ response to thapsigargin and also increased the rate of the Ca2+ rise induced by thapsigargin. In bovine adrenocortical microsomes, thapsigargin inhibited the ATP-dependent filling of Ca2+ pools and caused a dose-dependent rise in extravesicular Ca2+ levels when added to previously loaded microsomes. The thapsigargin-releasable Ca2+ pool in adrenal microsomes was larger than the inositol 1,4,5-trisphosphate (Ins(1,4,5)P3)-sensitive Ca2+ pool but only slightly greater than the GTP-releasable pool. Ins(1,4,5)P3-induced Ca2+ release was reduced markedly when ATP-dependent Ca2+ loading of the microsomes was prevented by prior addition of thapsigargin. However, the subsequent Ca2+ response to Ins(1,4,5)P3 was consistently better preserved after the addition of thapsigargin to microsomes preloaded with Ca2+. This difference suggests that although Ca2+ uptake by the Ins(1,4,5)P3-responsive pool is also sensitive to thapsigargin, once filled, this pool shows a slower passive leakage than other thapsigargin-sensitive pools. These findings indicate that thapsigargin increases [Ca2+]i by inhibiting Ca2+ uptake into multiple intracellular Ca2+ pools and by also promoting entry of extracellular Ca2+. The AII-responsive and thapsigargin-sensitive Ca2+ pools are largely coincident in adrenal cells, but there is a component of agonist-induced Ca2+ influx which is not mimicked by thapsigargin, and not all of the thapsigargin-sensitive Ca2+ pool is responsive to Ins(1,4,5)P3. C1 NICHHD, ENDOCRINOL & REPROD RES BRANCH, BLDG 10, RM B1L400, BETHESDA, MD 20892 USA. ROYAL DANISH SCH PHARM, DEPT CHEM BC, DK-2100 COPENHAGEN, DENMARK. FU NICHD NIH HHS [HD07383-03] NR 31 TC 94 Z9 94 U1 0 U2 1 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 OCT 5 PY 1991 VL 266 IS 28 BP 18635 EP 18641 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GJ472 UT WOS:A1991GJ47200038 PM 1917986 ER PT J AU LAKATOS, S MINTON, AP AF LAKATOS, S MINTON, AP TI INTERACTIONS BETWEEN GLOBULAR-PROTEINS AND F-ACTIN IN ISOTONIC SALINE SOLUTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SEDIMENTATION EQUILIBRIUM; CONTAINING-FILAMENTS; GLYCOLYTIC ENZYMES; BINDING PROTEINS; SKELETAL-MUSCLE; A-II; ALDOLASE; ASSOCIATION; METABOLISM AB Solutions of each of three different globular proteins (cytochrome c, chromophorically labeled serum albumin, and chromophorically labeled aldolase), mixed with another unlabeled globular protein or with fibrous actin, were prepared in pH 8.0 Tris-HCl buffer containing 0.15 M NaCl. Each solution was centrifuged at low speed, at 5-degrees-C, until unassociated globular protein in solution achieved sedimentation equilibrium. Individual absorbance gradients of both macrosolutes in the mixtures subsequent to centrifugation were obtained via optical scans of the centrifuge tubes at two wavelengths. The gradients of each macrosolute in mixtures of two globular proteins revealed no association of globular proteins under the conditions of these experiments, but perturbation of the gradients of serum albumin, aldolase, and cytochrome c in the presence of F-actin indicated association of all three globular proteins with F-actin. Perturbation of actin gradients in the presence of serum albumin and aldolase suggested partial depolymerization of the F-actin by the globular protein. Analysis of the data with a simple phenomenological model relating free globular protein, bound globular protein, and total actin concentration provided estimates of the respective equilibrium constants for association of serum albumin and aldolase with F-actin, under the conditions of these experiments, of the order of 0.1-mu-M-1. C1 NIDDKD, BIOCHEM PHARMACOL LAB, BETHESDA, MD 20892 USA. NR 41 TC 27 Z9 28 U1 0 U2 1 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 OCT 5 PY 1991 VL 266 IS 28 BP 18707 EP 18713 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GJ472 UT WOS:A1991GJ47200048 PM 1655757 ER PT J AU CORJAY, MH DOBRZANSKI, DJ WAY, JM VIALLET, J SHAPIRA, H WORLAND, P SAUSVILLE, EA BATTEY, JF AF CORJAY, MH DOBRZANSKI, DJ WAY, JM VIALLET, J SHAPIRA, H WORLAND, P SAUSVILLE, EA BATTEY, JF TI 2 DISTINCT BOMBESIN RECEPTOR SUBTYPES ARE EXPRESSED AND FUNCTIONAL IN HUMAN LUNG-CARCINOMA CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GASTRIN-RELEASING PEPTIDE; PROTEIN-KINASE-C; SWISS 3T3 CELLS; SEQUENCE-ANALYSIS; GROWTH-FACTORS; CANCER; GENE; CALCIUM; GUANINE; LINES AB Bombesin-like peptides have been implicated as autocrine growth factors influencing the pathogenesis and progression of some human lung carcinoma cells. To determine the pharmacologic and structural properties of the bombesin receptors expressed in human lung carcinoma cells, cDNA clones encoding a human gastrin-releasing peptide receptor (GRP-R) and a pharmacologically distinct neuromedin-B preferring bombesin-receptor (NMB-R) were isolated from a human small cell lung carcinoma cell line (NCI-H345). After expression in Xenopus oocytes, a GRP-R-specific antagonist was effective in blocking responses elicited from the cloned GRP-R, but not the NMB-R. Both GRP-R and NMB-R mRNA expression was detected at varying levels in a panel of human lung cancer cell lines. These results indicate heterogeneity of bombesin receptor subtypes exists in human lung carcinoma cells and should be considered in the design of bombesin receptor antagonists intended to inhibit tumor cell growth. C1 NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. MONTREAL GEN HOSP,DIV ONCOL,MONTREAL H3G 1A4,QUEBEC,CANADA. RP CORJAY, MH (reprint author), NINCDS,NEUROCHEM LAB,BLDG 36,ROOM 4D20,BETHESDA,MD 20892, USA. NR 44 TC 200 Z9 204 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 OCT 5 PY 1991 VL 266 IS 28 BP 18771 EP 18779 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GJ472 UT WOS:A1991GJ47200057 PM 1655761 ER PT J AU PREVIATO, L PARROTT, CL SANTAMARINAFOJO, S BREWER, HB AF PREVIATO, L PARROTT, CL SANTAMARINAFOJO, S BREWER, HB TI TRANSCRIPTIONAL REGULATION OF THE HUMAN LIPOPROTEIN-LIPASE GENE IN 3T3-L1 ADIPOCYTES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEVELOPMENTAL REGULATION; INSULIN REGULATION; EXPRESSION; CELLS; DNA; BINDING; HORMONE; PROTEIN; METABOLISM; POLYMERASE AB Lipoprotein lipase (LPL), a key enzyme in normal lipoprotein metabolism, has a complex pattern of regulation and tissue-specific expression. Several potential binding sites for transcription factors, including the recognition sequences for CCAAT/enhancer-binding protein and octamer-binding proteins (Oct) have been described in the 5'-flanking region of the human LPL gene. To identify elements which regulate the expression of LPL in adipocytes, plasmids containing deletion mutants of the 5'-LPL promoter region and the luciferase reporter gene were transfected in 3T3-L1 adipocytes. Deletions at -724, -565, -461, -368, -232, -167, -92, -35, and -17 relative to the transcriptional start site modified transcription from 100 to 162, 194, 185, 128, 63, 53, 29, and 0%, respectively, indicating the presence of negative (-724 to -565) and positive (-368 to -35) cis-acting regulatory elements. Transfection of HepG2 cells, which do not synthesize LPL, with the same constructs resulted in a similar pattern of expression for the majority of the deletions. However, deletions between -724 and -368 base pairs resulted in a 75-100% increase in transcription in 3T3 adipocytes but not in HepG2 cells, indicating the presence of tissue-specific regulatory element(s) in this region. An important regulatory element affecting LPL transcription in adipocytes was identified by gel mobility shift assays and DNase I footprint analysis. Using these techniques, a nuclear protein(s) in 3T3-L1 adipocytes was shown to bind specifically to a fragment which included the proximal octamer recognition site (from -46 to -39) present in the LPL promoter. The DNA-protein complex comigrates with an electrophoretic band containing the Oct-1-DNA complex in BJA-B nuclear extracts and the DNA-protein complex was selectively competed only by DNA fragments containing the octamer sequence. Preincubation of 3T3-L1 nuclear extracts with an antibody directed against the POU domain of Oct-1 inhibited the formation of the DNA-protein complex. Deletion of the proximal octanucleotide motif from the plasmid containing the -461 fragment of the LPL promoter, resulted in a 79 and 76% decrease in the level of expression in transfected 3T3-L1 adipocytes and HepG2 hepatocytes, respectively. These combined results have established that the expression of LPL in adipocytes is modulated by multiple positive and negative regulatory elements within the 5'-flanking region of the LPL gene. A proximal octamer binding sequence which specifically interacts with a nuclear protein(s) that exhibits the characteristics of Oct-1 has been identified. Deletional analysis indicates that this transcription factor plays an important role in modulating the expression of LPL in 3T3-L1 adipocytes. C1 NHLBI,MOLEC DIS BRANCH,9000 ROCKVILLE PIKE,BLDG 10-7N117,BETHESDA,MD 20892. NR 45 TC 49 Z9 52 U1 2 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 5 PY 1991 VL 266 IS 28 BP 18958 EP 18963 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GJ472 UT WOS:A1991GJ47200084 PM 1918010 ER PT J AU BOBO, L MUNOZ, B VISCIDI, R QUINN, T MKOCHA, H WEST, S AF BOBO, L MUNOZ, B VISCIDI, R QUINN, T MKOCHA, H WEST, S TI DIAGNOSIS OF CHLAMYDIA-TRACHOMATIS EYE INFECTION IN TANZANIA BY POLYMERASE CHAIN-REACTION ENZYME-IMMUNOASSAY SO LANCET LA English DT Article ID FIELD; DNA; REINFECTION AB Detection of Chlamydia trachomatis eye infection is largely unsatisfactory by standard laboratory methods. A polymerase chain reaction/enzyme immunoassay (PCR-EIA) that had previously been successful for diagnosis of genital C trachomatis infection was compared with direct antibody immunofluorescence (DFA) for detection of the organism in conjunctival scrapes. 234 Tanzanian children aged 1-7 years living in a village that had had no previous trachoma control programme were classified clinically as having no sign of trachoma (0) n = 97, follicular trachoma (TF) n = 100, or intense inflammatory trachoma with or without TF (TI +/- TF) n = 37. PCR-EIA detected C trachomatis in 24%, 54%, and 95% of subjects, respectively, compared with elementary body (EB) detection by DFA of 1%, 28%, and 60%, respectively. Overall prevalence of chlamydial eye infection was 22% by DFA compared with 48% by PCR-EIA. Of subjects with chlamydial DNA at pretreatment, 103 (92%) had no detectable chlamydial DNA at the end of 4 weeks of ocular tetracycline. The findings show that PCR-EIA is likely to affect trachoma diagnosis and epidemiology because of the increased sensitivity for detection of C trachomatis in all clinical groups; the less stringent requirements for specimen collection and transport make this method suitable for field use. Moreover, the semi-quantitative aspect of PCR-EIA may be useful for monitoring a decrease in chlamydial DNA after treatment. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DIV INFECT DIS,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,WILMER INST,DANA CTR PREVENT OPHTHALMOL,BALTIMORE,MD 21205. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. KONGWA TRACHOMA PROJECT,KONGWA,TANZANIA. RP BOBO, L (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205, USA. FU NIAID NIH HHS [2 PO1 AI 16959-09, N01 AI 52579] NR 20 TC 78 Z9 79 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 OCT 5 PY 1991 VL 338 IS 8771 BP 847 EP 850 DI 10.1016/0140-6736(91)91502-L PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA GH945 UT WOS:A1991GH94500004 PM 1681215 ER PT J AU WEINGARTNER, HJ ECKARDT, MJ HOMMER, DW MENDELSON, W WOLKOWITZ, OM AF WEINGARTNER, HJ ECKARDT, MJ HOMMER, DW MENDELSON, W WOLKOWITZ, OM TI SPECIFICITY OF MEMORY IMPAIRMENTS WITH TRIAZOLAM USE SO LANCET LA English DT Letter C1 NIAAA,CLIN STUDIES LAB,ROCKVILLE,MD 20852. UNIV WASHINGTON,DEPT PSYCHIAT,SEATTLE,WA 98195. UNIV WASHINGTON,VET ADM HOSP,GRCC,SEATTLE,WA 98195. SUNY STONY BROOK,DEPT PSYCHIAT,STONY BROOK,NY 11794. UNIV CALIF SAN FRANCISCO,DEPT PSYCHIAT,SAN FRANCISCO,CA 94143. RP WEINGARTNER, HJ (reprint author), NIA,GERONTOL RES CTR,COGNIT SECT,BALTIMORE,MD 21224, USA. NR 7 TC 13 Z9 13 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 OCT 5 PY 1991 VL 338 IS 8771 BP 883 EP 884 DI 10.1016/0140-6736(91)91534-2 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA GH945 UT WOS:A1991GH94500030 PM 1681231 ER PT J AU STEHLING, MK TURNER, R MANSFIELD, P AF STEHLING, MK TURNER, R MANSFIELD, P TI ECHO-PLANAR IMAGING - MAGNETIC-RESONANCE-IMAGING IN A FRACTION OF A SECOND SO SCIENCE LA English DT Article ID INTRAVOXEL INCOHERENT MOTION; CENTRAL-NERVOUS-SYSTEM; HUMAN FETUS INUTERO; HUMAN-BRAIN MOTION; CEREBROSPINAL-FLUID; FLASH MRI; HUMAN-HEART; FLIP-ANGLE; NMR; DIFFUSION AB Progress has recently been made in implementing magnetic resonance imaging (MRI) techniques that can be used to obtain images in a fraction of a second rather than in minutes. Echo-planar imaging (EPI) uses only one nuclear spin excitation per image and lends itself to a variety of critical medical and scientific applications. Among these are evaluation of cardiac function in real time, mapping of water diffusion and temperature in tissue, mapping of organ blood pool and perfusion, functional imaging of the central nervous system, depiction of blood and cerebrospinal fluid flow dynamics, and movie imaging of the mobile fetus in utero. Through shortened patient examination times, higher patient throughput, and lower cost per MRI examination, EPI may become a powerful tool for early diagnosis of some common and potentially treatable diseases such as ischemic heart disease, stroke, and cancer. C1 SIEMENS AG,W-8520 ERLANGEN,GERMANY. NIH,CARDIAC ENERGET LAB,BETHESDA,MD 20892. UNIV NOTTINGHAM,DEPT PHYS,NOTTINGHAM NG7 2RD,ENGLAND. RP STEHLING, MK (reprint author), FRIEDRICH ALEXANDER UNIV ERLANGEN,DEPT CARDIOL,W-8520 ERLANGEN,GERMANY. RI Turner, Robert/C-1820-2008 NR 124 TC 329 Z9 335 U1 6 U2 42 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 4 PY 1991 VL 254 IS 5028 BP 43 EP 50 DI 10.1126/science.1925560 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GH605 UT WOS:A1991GH60500026 PM 1925560 ER PT J AU PELLETIER, J BRUENING, W LI, FP HABER, DA GLASER, T HOUSMAN, DE AF PELLETIER, J BRUENING, W LI, FP HABER, DA GLASER, T HOUSMAN, DE TI WT1 MUTATIONS CONTRIBUTE TO ABNORMAL GENITAL SYSTEM-DEVELOPMENT AND HEREDITARY WILMS-TUMOR SO NATURE LA English DT Article ID SEX-DETERMINING REGION; GENE; DNA; CHROMOSOME-11; DELETION AB WILMS' tumour (WT), aniridia, genitourinary abnormalities and mental retardation form a symptom group (WAGR syndrome) associated with hemizygous deletions of DNA in chromosome band 11p13 (refs 1, 2). However, it has not been clear whether hemizygosity at a single locus contributes to more than one phenotype. The tumour suppressor gene for Wilms' tumour, WT1, has been characterized 3,4: it is expressed at high levels in the glomeruli of the kidney 5, as well as the gonadal ridge of the developing gonad 5, the Sertoli cells of the testis 6 and the epithelial and granulosa cells of the ovary 6, suggesting a developmental role in the genital system in addition to the kidney. We now report constitutional mutations within the WT1 genes of two individuals with a combination of WT and genital abnormalities as evidence of a role for a recessive oncogene in mammalian development. C1 MCGILL UNIV,CTR CANC,MONTREAL H3G 1Y6,QUEBEC,CANADA. NCI,DIV CANC ETIOL,CLIN EPIDEMIOL BRANCH,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV BIOSTAT & EPIDEMIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,BRIGHAM & WOMENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. RP PELLETIER, J (reprint author), MIT,CTR CANC RES,CAMBRIDGE,MA 02139, USA. NR 16 TC 368 Z9 371 U1 1 U2 3 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD OCT 3 PY 1991 VL 353 IS 6343 BP 431 EP 434 DI 10.1038/353431a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GH606 UT WOS:A1991GH60600057 PM 1654525 ER PT J AU PANZA, JA EPSTEIN, SE QUYYUMI, AA AF PANZA, JA EPSTEIN, SE QUYYUMI, AA TI CIRCADIAN VARIATION IN VASCULAR TONE AND ITS RELATION TO ALPHA-SYMPATHETIC VASOCONSTRICTOR ACTIVITY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SUDDEN CARDIAC DEATH; ATHEROSCLEROTIC CORONARY-ARTERIES; ACUTE MYOCARDIAL-INFARCTION; ESSENTIAL-HYPERTENSION; MORNING INCREASE; ANGINA-PECTORIS; ADRENERGIC VASOCONSTRICTION; MEDIATED VASOCONSTRICTION; PLATELET AGGREGABILITY; DIURNAL-VARIATION AB Background. The frequency of several cardiovascular events, such as myocardial infarction, sudden death, and stroke, is increased during the early morning hours. There is also a similar circadian pattern in several physiologic variables, including blood pressure, suggesting that certain dynamic processes may contribute to the circadian distribution and onset of acute events. Methods. To determine whether there are circadian variations in vascular tone and to investigate their underlying mechanisms, we measured blood flow and vascular resistance in the forearm and their responses to phentolamine (an alpha-adrenergic-antagonist drug) and sodium nitroprusside (a direct vasodilator) in 12 normal subjects 7 men and 5 women; mean age [+/- SD], 44 +/- 9 years) at three different times of day (7 a.m., 2 p.m., and 9 p.m.). The drugs were infused into the brachial artery, and the responses were measured by strain-gauge plethysmography. Results. The basal forearm vacular resistance was significantly higher, and the blood flow significantly lower, in the morning than in the afternoon and evening (mean vascular resistance, 31 +/- 8, 25 +/- 6, and 22 +/- 7 mm Hg per milliliter per minute per 100 ml of forearm volume, respectively; P < 0.01). The vasodilator effect of phentolamine was also significantly greater in the morning (mean decrease in vascular resistance, 38 +/- 6 percent) than in the afternoon (26 +/- 6 percent) and evening (21 +/- 7 percent) (P < 0.05). Consequently, there was no circadian variation in vascular resistance or blood flow after the infusion of this drug. In contrast, the vasodilation in response to sodium nitroprusside was similar at all three times of day. Conclusions. There is a circadian rhythm in basal vascular tone, due either partly or entirely to increased alpha-sympathetic vasoconstrictor activity during the morning. This variation may contribute to higher blood pressure and the increased incidence of cardiovascular events at this time of day. RP PANZA, JA (reprint author), NHLBI,BLDG 10,RM 7B-15,BETHESDA,MD 20892, USA. NR 43 TC 393 Z9 396 U1 0 U2 5 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 OCT 3 PY 1991 VL 325 IS 14 BP 986 EP 990 DI 10.1056/NEJM199110033251402 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA GH447 UT WOS:A1991GH44700002 PM 1886635 ER PT J AU SHARPE, LG PILOTTE, NS MITCHELL, WM DESOUZA, EB AF SHARPE, LG PILOTTE, NS MITCHELL, WM DESOUZA, EB TI WITHDRAWAL OF REPEATED COCAINE DECREASES AUTORADIOGRAPHIC [H-3] MAZINDOL-LABELING OF DOPAMINE TRANSPORTER IN RAT NUCLEUS-ACCUMBENS SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Note DE SENSITIZATION; STRIATUM; DOWN-REGULATION; DOPAMINE UPTAKE ID NOREPINEPHRINE UPTAKE; H-3 DOPAMINE; UPTAKE SITES; STRIATUM; BRAIN AB The in vitro autoradiographic distribution of desipramine-insensitive specific [H-3]mazindol binding sites (labelling the dopamine transporter) was determined in brain sections from rats receiving repeated i.v. infusions of saline or cocaine (1 mg/kg, every 12 min for 2 h/day), for 10 days. Brains were removed either within 15 min of or 10 days after the last treatment. A marked dorsal-to-ventral gradient in [H-3]mazindol binding appeared in the striatum with the dorsal caudate putamen showing the greatest binding and the medial shell of the nucleus accumbens the least. Cocaine-associated changes in [H-3]mazindol-labelled dopamine uptake sites occurred only in the nucleus accumbens (57 and 66% decrease in the lateral core and medial shell, respectively), of animals 10 days after the last treatment. Down-regulation of the dopamine transporter in the nucleus accumbens by withdrawal of chronic cocaine may be one of the mechanisms involved in cocaine's long-term abstinence effects. RP SHARPE, LG (reprint author), NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224, USA. NR 10 TC 114 Z9 114 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD OCT 2 PY 1991 VL 203 IS 1 BP 141 EP 144 DI 10.1016/0014-2999(91)90804-Y PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GN303 UT WOS:A1991GN30300022 PM 1797552 ER PT J AU INSEL, TR WINSLOW, JT AF INSEL, TR WINSLOW, JT TI CENTRAL ADMINISTRATION OF OXYTOCIN MODULATES THE INFANT RATS RESPONSE TO SOCIAL-ISOLATION SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Note DE OXYTOCIN; ULTRASONIC VOCALIZATION; ANXIETY; THERMOREGULATION; AFFILIATION ID VASOPRESSIN; BRAIN; RECEPTORS; AUTORADIOGRAPHY AB Several lines of evidence suggest that oxytocin modulates the formation and maintenance of social bonds. In the current experiments we investigated the influence of centrally and peripherally administered oxytocin on the behavior of 6-8 day old rat pups during brief periods of social isolation. Ultrasonic vocalizations emitted by isolated pups were decreased following i.c.v. administration of oxytocin, at doses (500, 1000 ng) which did not affect motor activity. S.c. administered oxytocin (1.10-mu-g) produced a biphasic change in ultrasonic vocalizations, depending on dose. Central administration of the oxytocin antagonist (d(CH2)5[Tyr(Me)2,Thr4, Tyr-NH29]OVT) (OTA, 500 ng) did not measurably affect pup behavior by itself but did block the decrease in calls following central but not peripheral administration of oxytocin. These data demonstrate that oxytocin via its central receptor can regulate the response to social isolation. RP INSEL, TR (reprint author), NIMH,ANIM CTR,CLIN SCI LAB,POB 289,POOLESVILLE,MD 20837, USA. NR 12 TC 114 Z9 115 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD OCT 2 PY 1991 VL 203 IS 1 BP 149 EP 152 DI 10.1016/0014-2999(91)90806-2 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GN303 UT WOS:A1991GN30300024 PM 1665788 ER PT J AU JUENGST, ET AF JUENGST, ET TI PRIORITIES IN PROFESSIONAL ETHICS AND SOCIAL-POLICY FOR HUMAN-GENETICS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP JUENGST, ET (reprint author), NIH,NATL CTR HUMAN GENOME RES,PROGRAM ETH LEGAL & SOCIAL IMPLICAT,BETHESDA,MD 20892, USA. OI Juengst, Eric/0000-0002-8374-5774 NR 16 TC 15 Z9 15 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 OCT 2 PY 1991 VL 266 IS 13 BP 1835 EP 1836 DI 10.1001/jama.266.13.1835 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA GG551 UT WOS:A1991GG55100040 PM 1890713 ER PT J AU PEARSON, JW FOGLER, WE VOLKER, K USUI, N GOLDENBERG, SK GRUYS, E RIGGS, CW KOMSCHLIES, K WILTROUT, RH TSURUO, T PASTAN, I GOTTESMAN, MM LONGO, DL AF PEARSON, JW FOGLER, WE VOLKER, K USUI, N GOLDENBERG, SK GRUYS, E RIGGS, CW KOMSCHLIES, K WILTROUT, RH TSURUO, T PASTAN, I GOTTESMAN, MM LONGO, DL TI REVERSAL OF DRUG-RESISTANCE IN A HUMAN COLON CANCER XENOGRAFT EXPRESSING MDR1 COMPLEMENTARY-DNA BY INVIVO ADMINISTRATION OF MRK-16 MONOCLONAL-ANTIBODY SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ENHANCED THERAPEUTIC EFFICACY; CLONED CELL-LINES; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; TUMOR-CELLS; P388 LEUKEMIA; ATHYMIC MICE; GENE; ADRIAMYCIN; TRANSPORT AB One strategy to overcome multidrug resistance in neoplasia is to inhibit the gp170 glycoprotein (relative molecular mass, 170 000) that functions as a plasma membrane, energy-dependent, drug-efflux pump. The human colon cancer cell line HT-29, which grows as an ascitic tumor in athymic NCr-nu/nu nude mice, was made multidrug resistant by infection with an MDR1 (also known as PGY1) retrovirus. Referred to as HT-29mdr1, it was used to study reversal of drug resistance in vivo by the anti-P-glycoprotein monoclonal antibody MRK-16. Flow cytometry and radioimmunoassay demonstrated a marked increase in MRK-16 reactivity on HT-29mdr1 cells as compared with its reactivity on the parental, uninfected cell line (HT-29par). The 50% inhibitory concentrations (IC50) of vincristine on HT-29par and HT-29mdr1 cells were 2.5 and 15 ng/mL, respectively. The MRK-16 monoclonal antibody did not affect the vincristine sensitivity of the HT-29par cells. Pretreatment of HT-29mdr1 cells with 10-mu-g/mL MRK-16 in tissue culture partially restored the vincristine sensitivity (IC50 = 7 ng/mL). This modulation of vincristine sensitivity by MRK-16 was then tested in vivo. The median survival times of mice given intraperitoneal transplants of 5 x 10(6) HT-29par or HT-29mdr1 were 37 and 39 days, respectively. Treatment of mice with 1 mg/kg vincristine weekly for 3 weeks, beginning 10 days after tumor injection, resulted in a significant increase in the median survival time of the HT-29par tumor-bearing mice (68 days, P < .0001), but it had no effect on the HT-29mdr1 tumor-bearing mice. However, treatment of mice bearing the HT-29mdr1 tumor with MRK-16 before vincristine therapy reversed the resistance to the drug (median survival time = 64 days, P < .0001). The MRK-16 monoclonal antibody alone had no effect on the median survival time of mice given an injection of either HT-29par or HT-29mdr1 cells. These results suggest that strategies employing monoclonal antibody against gp170 may be clinically useful to reverse multidrug resistance. C1 NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892. NCI,DIV CANC BIOL,CELL BIOL LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,DATA MANAGEMENT SERV INC,FREDERICK,MD 21702. JAPANESE FDN CANC RES,CTR CANC CHEMOTHERAPY,TOKYO 170,JAPAN. NCI,DIV CANC BIOL,MOLEC BIOL LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,OYNCORP,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RP PEARSON, JW (reprint author), NCI,FREDERICK CANC RES & DE,DIV CANC TREATMENT,EXPTL IMMUNOL LAB,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01CO-74102] NR 34 TC 72 Z9 73 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 OCT 2 PY 1991 VL 83 IS 19 BP 1386 EP 1391 DI 10.1093/jnci/83.19.1386 PG 6 WC Oncology SC Oncology GA GG761 UT WOS:A1991GG76100012 PM 1681110 ER PT J AU VANNEVEL, P AF VANNEVEL, P TI TREATMENT PROGRAM - CONVENTIONAL AND UNCONVENTIONAL - RESPONSE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter RP VANNEVEL, P (reprint author), NCI,BLDG 31,RM 10A29,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 2 PY 1991 VL 83 IS 19 BP 1421 EP 1421 DI 10.1093/jnci/83.19.1421-a PG 1 WC Oncology SC Oncology GA GG761 UT WOS:A1991GG76100023 ER PT J AU DIMITROV, DS GOLDING, H BLUMENTHAL, R AF DIMITROV, DS GOLDING, H BLUMENTHAL, R TI INITIAL-STAGES OF HIV-1 ENVELOPE GLYCOPROTEIN-MEDIATED CELL-FUSION MONITORED BY A NEW ASSAY BASED ON REDISTRIBUTION OF FLUORESCENT DYES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HTLV-III/LAV ENVELOPE; T-CELLS; SYNCYTIUM FORMATION; INFLUENZA HEMAGGLUTININ; AIDS RETROVIRUS; MEMBRANE-FUSION; VACCINIA VIRUS; INFECTION; RECEPTOR AB Membrane fusion is an essential step in the infection of permissive cells with human immunodeficiency virus (HIV). Infected cells frequently fuse with each other, and then progress to form multinucleated giant cells (syncytia). To gain insight into mechanisms of HIV env-mediated membrane fusion, we developed a new assay for studying the initial events. The assay is based on the redistribution of fluorescent markers between membranes and cytoplasm of adjacent cells examined by means of fluorescence video microscopy. Membrane fusion between HIV-1 envelope glycoprotein (gp120/41) expressing effector cells and CD4+ target cells was observed 90 min after the association of cells, whereas the first syncytia only became apparent after 5 h. Moreover, membrane fusion events were observed under conditions where no syncytia were detected, for example, when the effector:target cell ratio was greater than 100:1, or less than 1:100. A significant number of cells with fused membranes were not involved in the syncytia. In order to determine whether quantitative differences in receptor expression might influence the extent of membrane fusion, we used laboratory-selected variants of CEM cells that differ in their expression of CD4. We found that CD4 is required on the target membrane for HIV env-mediated membrane fusion, but its extent is only partially dependent on CD4 surface concentration. The ability of those CEM variants to take part in HIV env-mediated membrane fusion did not correlate with their capacity to form syncytia. These findings indicate that additional steps are needed to form syncytia after membrane fusion. C1 NCI,MEMBRANE STRUCT & FUNCT SECT,LMMB,BLDG 10,RM 4B56,BETHESDA,MD 20892. US FDA,CBER,DIV VIROL,BETHESDA,MD 20892. NR 44 TC 48 Z9 48 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 OCT PY 1991 VL 7 IS 10 BP 799 EP 805 DI 10.1089/aid.1991.7.799 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA GM204 UT WOS:A1991GM20400003 PM 1742075 ER PT J AU LIGETI, L HINES, K DORA, E SINNWELL, T HUANG, MT MCLAUGHLIN, AC AF LIGETI, L HINES, K DORA, E SINNWELL, T HUANG, MT MCLAUGHLIN, AC TI CEREBRAL BLOOD-FLOW AND METABOLIC-RATE IN THE CONSCIOUS, FREELY MOVING RAT - THE EFFECTS OF HYPERCAPNIA, AND ACUTE ETHANOL ADMINISTRATION SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE CEREBRAL BLOOD FLOW; CEREBRAL OXYGEN CONSUMPTION; CEREBRAL BLOOD GLUCOSE CONSUMPTION; RAT; ALCOHOL ID OXYGEN-CONSUMPTION; GLUCOSE CONSUMPTION; BRAIN AB We propose a simple method that can be used to measure cerebral blood flow (CBF), cerebral oxygen consumption (CMRO2), and cerebral glucose consumption (CMRglu) in the conscious, freely moving rat. The method is based on the classical Kety-Schmidt approach, and uses a chronic cannula in the confluens sinuum. We tested the method by investigating the response of CBF, CMRO2, and CMRglu to hypercapnia and used the approach to investigate the effects of acute alcohol administration. Severe hypercapnia (PaCO2 approximately 80 mmHg) increased the CBF by a factor of 3.5, decreased the CMRO2 by 30%, and had no significant effect on the CMRglu. Under normocapnic conditions moderate blood alcohol levels (100-200 mg%) caused no significant effects on CBF, CMRO2, or CMRglu, but high blood alcohol levels (250-400 mg%) decreased all three parameters by approximately 25%. Under hypercapnic conditions high blood alcohol levels had no effect on CBF, CMRO2, and CMRglu. RP LIGETI, L (reprint author), NIAAA,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 24 TC 9 Z9 9 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 OCT PY 1991 VL 15 IS 5 BP 766 EP 770 DI 10.1111/j.1530-0277.1991.tb00597.x PG 5 WC Substance Abuse SC Substance Abuse GA GL409 UT WOS:A1991GL40900005 PM 1755506 ER PT J AU HELLEVUO, K HOFFMAN, PL TABAKOFF, B AF HELLEVUO, K HOFFMAN, PL TABAKOFF, B TI ETHANOL FAILS TO MODIFY (H-3)GR65630 BINDING TO 5-HT3 RECEPTORS IN NCB-20 CELLS AND IN RAT CEREBRAL MEMBRANES SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ETHANOL; 5-HT3 RECEPTOR BINDING; [H-3]GR65630; RAT BRAIN; NCB-20 CELLS ID 5-HYDROXYTRYPTAMINE RECEPTOR; ADENYLATE-CYCLASE; RADIOLIGAND BINDING; RECOGNITION SITES; IDENTIFICATION; CORTEX; PHARMACOLOGY; RELEASE; LIGAND; BRAIN AB Low concentrations of ethanol have been found to enhance the electrophysiologic effect of serotonin (5-HT) acting at 5-HT3 receptors on NCB-20 cells. To determine whether this action of ethanol reflects a change in the agonist-receptor interaction, the effect of ethanol (100 mM) on agonist and antagonist binding to 5-HT3 receptor was studied in vitro in membranes from NCB-20 cells and from cortex plus hippocampus of rat. The antagonist [H-3]GR65630 was used to label 5-HT3 recognition sites. Ethanol did not change the characteristics of saturable [H-3]GR65630 binding in either membrane preparation. In competition studies, the agonists 5-HT and 2-methyl-5-HT completely inhibited the binding of [H-3]GR65630 to NCB-20 cell membranes, while in brain membranes the maximum displacement of specific [H-3]GR65630 binding by 5-HT was approximately 30%. Ethanol decreased the affinity of the receptor for 2-methyl-5-HT, but not to 5-HT in NCB-20 cells, and had no effect on agonist binding in brain membranes. The results indicate that enhancement of 5-HT responses at 5-HT3 receptors by ethanol is not a result of changes in the equilibrium binding characteristics of the agonist. C1 NIAAA,DIV INTRAMURAL CLIN & BIOL RES,ROCKVILLE,MD 20852. NR 30 TC 19 Z9 19 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD OCT PY 1991 VL 15 IS 5 BP 775 EP 778 DI 10.1111/j.1530-0277.1991.tb00599.x PG 4 WC Substance Abuse SC Substance Abuse GA GL409 UT WOS:A1991GL40900007 PM 1755508 ER PT J AU JONES, JM VEECH, RL ABBASI, F YU, K YERALAN, O BRIEFEL, GR ANDERSON, J MEZEY, E AF JONES, JM VEECH, RL ABBASI, F YU, K YERALAN, O BRIEFEL, GR ANDERSON, J MEZEY, E TI ALTERED EXPRESSION OF HLA ANTIGENS AND CD16 FC-RECEPTORS ON LEUKOCYTES OF ALCOHOLIC SUBJECTS AND UREMIC PATIENTS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ACETATE; ALCOHOL; CD16; HEMODIALYSIS; HLA ID MAJOR HISTOCOMPATIBILITY COMPLEX; HUMAN PERIPHERAL-BLOOD; NATURAL-KILLER CELL; STAGE RENAL-DISEASE; CLASS-I MHC; SODIUM-ACETATE; BETA-2-MICROGLOBULIN; DIALYSIS; ETHANOL; GAMMA AB The possible influences of ethanol and its metabolic product acetate on the surface expression of HLA class I and class II antigens and CD16 Fc receptors were examined. Fluorescent-labeled monoclonal antibodies and flow cytometry were used to measure these antigens on leukocytes from reference controls, subjects admitted for alcohol detoxification, uremic patients undergoing hemodialysis using Cuprophan dialyzers and fluids containing 4 to 37 mM acetate, and uremic patients that were not hemodialyzed. In comparison to the controls, the mean intensity of staining for class I antigens was not changed significantly on lymphocytes or monocytes from alcoholics but was depressed on cells from eight of 12 uremic patients. Interferon-gamma above 5 units/ml was detected in less than 15% of plasma samples from controls, uremic patients or alcoholics on admission but was detected in four of eight samples from alcoholics at discharge (2-4 days after admission). The intensity of staining for class II antigens was depressed by more than 50% on lymphocytes from alcoholics and uremic patients. The expression of HLA class I and class II antigens was depressed whether uremic patients were hemodialyzed or not. The percentage of lymphocytes expressing CD16 was depressed in three of seven alcoholics and five of seven hemodialyzed patients. In contrast, the percentage of monocytes expressing CD16 was increased in six of seven hemodialyzed patients and three of five uremic patients not undergoing hemodialysis suggesting activation of monocytes in these patients. Plasma levels of beta 2-microglobulin were elevated by 61% in alcoholics, 50-fold in hemodialyzed patients, and 26-fold in nonhemodialyzed uremic patients. Although alcoholics and hemodialyzed patients exhibited similar alterations in some of the parameters measured, the results did not indicate a significant role for acetate or hemodialysis with Cuprophan membranes in the alterations of membrane antigen expression. C1 NIAAA,METAB & MOLEC BIOL LAB,12501 WASHINGTON AVE,ROCKVILLE,MD 20852. NIDR,BETHESDA,MD 20892. NICHHD,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,INST MED,DEPT IMMUNOL & INFECT DIS,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,INST MED,DEPT MED,BALTIMORE,MD 21218. NR 51 TC 4 Z9 4 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 OCT PY 1991 VL 15 IS 5 BP 790 EP 795 DI 10.1111/j.1530-0277.1991.tb00602.x PG 6 WC Substance Abuse SC Substance Abuse GA GL409 UT WOS:A1991GL40900010 PM 1836713 ER PT J AU YANOVSKI, SZ AF YANOVSKI, SZ TI BULIMIA-NERVOSA - THE ROLE OF THE FAMILY PHYSICIAN (REPRINTED FROM DIAGNOST AND STAT MANUAL MENTAL-DISORDERS, 68-69, 1987) SO AMERICAN FAMILY PHYSICIAN LA English DT Article AB Bulimia nervosa is an eating disorder characterized by binge eating and purging. The disorder is estimated to occur in up to 5 percent of young women. Despite severe psychosocial impairment and potentially serious medical complications, patients do not usually reveal their bulimic behavior to a physician unless directly asked. Promising treatments include cognitive-behavioral psychotherapy and antidepressant medications. RP YANOVSKI, SZ (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,EATING DISORDERS UNIT,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD OCT PY 1991 VL 44 IS 4 BP 1231 EP 1238 PG 8 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA GJ517 UT WOS:A1991GJ51700015 PM 1927838 ER PT J AU YUSUF, S FURBERG, CD AF YUSUF, S FURBERG, CD TI ARE WE BIASED IN OUR APPROACH TO TREATING ELDERLY PATIENTS WITH HEART-DISEASE SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material ID ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED CLINICAL-TRIALS; UNSTABLE ANGINA; PREVENTION; MORTALITY C1 WAKE FOREST UNIV, BOWMAN GRAY SCH MED, DEPT PUBL HLTH SCI, WINSTON SALEM, NC 27103 USA. RP YUSUF, S (reprint author), NHLBI, DIV EPIDEMIOL & CLIN APPLICAT, CLIN TRIALS BRANCH, FED BLDG 5C10, BETHESDA, MD 20892 USA. NR 19 TC 25 Z9 25 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 1 PY 1991 VL 68 IS 9 BP 954 EP 956 DI 10.1016/0002-9149(91)90416-I PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA GG352 UT WOS:A1991GG35200020 PM 1927957 ER PT J AU MACLURE, M TRAVIS, LB WILLETT, W MACMAHON, B AF MACLURE, M TRAVIS, LB WILLETT, W MACMAHON, B TI A PROSPECTIVE COHORT STUDY OF NUTRIENT INTAKE AND AGE AT MENARCHE SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE DIET; NUTRITION; OBESITY; MENARCHE; MENSES; AGE; ADOLESCENCE ID BREAST-CANCER; CORPUS-LUTEUM; DIETARY FACTORS; FOOD FREQUENCY; BETA-CAROTENE; WOMEN; QUESTIONNAIRE; RISK; FAT; FERTILITY AB A cohort of 213 girls (aged 10 y, range +/- 9 mo) whose parents reported their dietary intakes (including nutritional supplements) using a semiquantitative food frequency questionnaire, was followed for 4 y until 82% of the 194 parents who responded to follow-up letters had reported that their daughters had had their first menstrual periods. The relative risk (RR) of menarche before age 12.5 y was 2.0 [95% confidence interval (CI) = 1.1-3.8] for the tallest girls (> 150 cm) compared with the shortest girls (< 130 cm). The RR was 2.1 (95% CI = 1.1-3.8) for the fattest girls [Quetelet's index of relative weight (in kg/m2) > 19] vs the leanest girls (< 15). After adjusting for height and Quetelet's index, menarcheal age was not associated with intake of energy nor energy-adjusted intake of protein, fat, or carbohydrate. The overall results are consistent with the hypothesis that nutritional factors influence age at menarche mainly through their effects on accumulation of adipose tissue. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,BOSTON,MA 02115. NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. RP MACLURE, M (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 06373, CA 09001] NR 47 TC 82 Z9 86 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 OCT PY 1991 VL 54 IS 4 BP 649 EP 656 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA GH337 UT WOS:A1991GH33700007 PM 1897472 ER PT J AU BHATHENA, SJ BERLIN, E JUDD, JT KIM, YC LAW, JS BHAGAVAN, HN BALLARDBARBASH, R NAIR, PP AF BHATHENA, SJ BERLIN, E JUDD, JT KIM, YC LAW, JS BHAGAVAN, HN BALLARDBARBASH, R NAIR, PP TI EFFECTS OF OMEGA-3-FATTY-ACIDS AND VITAMIN-E ON HORMONES INVOLVED IN CARBOHYDRATE AND LIPID-METABOLISM IN MEN SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE FISH-OIL FEEDING; OMEGA-3 FATTY ACIDS; VITAMIN-E; INSULIN; GLUCAGON; CORTISOL; DEHYDROEPIANDROSTERONE SULFATE; DHEA-S; GROWTH HORMONE; SOMATOMEDIN-C ID FISH-OIL CONCENTRATE; OBESE ZUCKER RATS; COD-LIVER OIL; CARDIOVASCULAR-DISEASE; DEHYDROEPIANDROSTERONE DHEA; DIABETES-MELLITUS; DIETARY LIPIDS; BHE RATS; INSULIN; GLUCOSE AB Forty healthy men were fed diets providing 40% of energy from fat and a minimum of 25 mg vitamin E for 28 wk. During the first 10 wk diets were supplemented with placebo, 15 g mixed fat/d. During the second 10 wk placebo was replaced by 15 g fish-oil concentrate/d. During the last 8 wk 200 mg vitamin E/d was added to fish oil. Compared with placebo, fish-oil feeding significantly increased plasma glucose and decreased triacylglycerol, insulin, glucagon, growth hormone, and somatomedin C. The changes in plasma cholesterol, cortisol, and dehydroepiandrosterone sulphate (DHEA-S) were not significant. Fish oil plus vitamin E further decreased insulin, growth hormone, and DHEA-S and reversed the effect of fish-oil on somatomedin C. The changes in glucose, glucagon, growth hormone, and cortisol were not significant. Thus, changes in plasma glucose and lipids caused by dietary fish oil alone and with fish oil plus vitamin E appear to be due to alterations in hormones involved in carbohydrate and lipid metabolism. C1 USDA,BELTSVILLE HUMAN NUTR RES CTR,LIPID NUTR LAB,BELTSVILLE,MD 20705. HOFFMANN LA ROCHE INC,NUTLEY,NJ 07110. NCI,DIV CANC PREVENT & CONTROL,CANCER PREVENT STUDIES BRANCH,BETHESDA,MD 20892. RP BHATHENA, SJ (reprint author), USDA,BELTSVILLE HUMAN NUTR RES CTR,CARBOHYDRATE NUTR LAB,BLDG 307 E,BELTSVILLE,MD 20705, USA. NR 57 TC 44 Z9 44 U1 0 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 OCT PY 1991 VL 54 IS 4 BP 684 EP 688 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA GH337 UT WOS:A1991GH33700012 PM 1832814 ER PT J AU FLORES, H AZEVEDO, MNA CAMPOS, FACS BARRETOLINS, MC CAVALCANTI, AA SALZANO, AC VARELA, RM UNDERWOOD, BA AF FLORES, H AZEVEDO, MNA CAMPOS, FACS BARRETOLINS, MC CAVALCANTI, AA SALZANO, AC VARELA, RM UNDERWOOD, BA TI SERUM VITAMIN-A DISTRIBUTION CURVE FOR CHILDREN AGED 2-6 Y KNOWN TO HAVE ADEQUATE VITAMIN-A STATUS - A REFERENCE POPULATION SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE VITAMIN-A DEFICIENCY; RELATIVE-DOSE-RESPONSE TEST; VITAMIN-A STATUS ID RELATIVE-DOSE-RESPONSE; TEST-RETEST REPRODUCIBILITY; GUATEMALAN ADULTS; MORTALITY; DEFICIENCY; INDICATOR; RETINOL; ISSUES AB Serum vitamin A was determined before and 30-45 d after the administration of 60.6 mg (212-mu-mol) vitamin A to 544 Brazilian children residing in slum areas of Recife. The frequency-distribution curves were compared in a subgroup of children whose vitamin A status was assessed initially by the relative-dose-response (RDR) test. The curves of children with negative (adequate status) and positive (inadequate status) RDR tests were different. The difference disappeared after supplementation. The shape of the distribution curve after supplementation was close to normal with a mean, median, and 95% confidence interval of 1.78 +/- 0.49, 1.68, and 1.02-2.90-mu-mol/L, respectively. The postsupplementation curve derived from this underprivileged child population may serve as a reference for diagnostic, surveillance, and program-evaluation purposes. C1 NEI,OFF INT PROGRAM ACTIV,BETHESDA,MD 20892. RP FLORES, H (reprint author), FED UNIV PERNAMBUCO,CTR HLTH SCI,DEPT NUTR,NUTR BIOCHEM LAB,RUA PROF NELSON CHAVES S-N,BR-50739 RECIFE,BRAZIL. NR 30 TC 39 Z9 44 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 OCT PY 1991 VL 54 IS 4 BP 707 EP 711 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA GH337 UT WOS:A1991GH33700016 PM 1897477 ER PT J AU DHARIWAL, KR HARTZELL, WO LEVINE, M AF DHARIWAL, KR HARTZELL, WO LEVINE, M TI ASCORBIC-ACID AND DEHYDROASCORBIC ACID MEASUREMENTS IN HUMAN PLASMA AND SERUM SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE VITAMIN-C; ASCORBIC ACID; DEHYDROASCORBIC ACID; HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY; SERUM; PLASMA ID COULOMETRIC ELECTROCHEMICAL DETECTION; PERFORMANCE LIQUID-CHROMATOGRAPHY; NOREPINEPHRINE BIOSYNTHESIS; DIABETES-MELLITUS; LEUKOCYTES; CELLS AB We investigated whether circulating ascorbic acid in humans is protein bound or free and whether ascorbic acid exists in its reduced form alone as ascorbic acid or in its reduced and oxidized forms as ascorbic acid and dehydroascorbic acid, respectively. Ascorbic acid and dehydroascorbic acid were determined by using HPLC with coulometric electrochemical detection, and protein binding was determined by centrifugal ultrafiltration. Ascorbic acid was free in plasma and serum of normal, healthy volunteers, 10 men and 10 women. Ascorbic acid was detectable only in its reduced form. However, dehydroascorbic acid could be made to appear in samples processed under oxidizing conditions. Because circulating ascorbic acid is free and is detected only as reduced vitamin, ascorbic acid may be available without intermediates for peripheral utilization. Dehydroascorbic acid may not be present in plasma and serum of normal humans unless assay conditions permit ascorbic acid oxidation. C1 NIH,BLDG 8,ROOM 415,BETHESDA,MD 20892. NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD. NR 30 TC 197 Z9 198 U1 0 U2 11 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 OCT PY 1991 VL 54 IS 4 BP 712 EP 716 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA GH337 UT WOS:A1991GH33700017 PM 1897478 ER PT J AU MESSINA, M AF MESSINA, M TI PHYTATES POTENTIAL ROLE IN REDUCING COLON-CANCER RISK SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Letter ID LARGE INTESTINAL CANCER; INOSITOL HEXAPHOSPHATE; CELL-PROLIFERATION; PHYTIC ACID; F344 RATS; SUPPRESSION RP MESSINA, M (reprint author), NCI,DIV CANC PREVENT & CONTOL,EXECUTIVE PLAZA N,ROOM 212C,BETHESDA,MD 20892, USA. NR 11 TC 4 Z9 4 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 OCT PY 1991 VL 54 IS 4 BP 762 EP 763 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA GH337 UT WOS:A1991GH33700027 PM 1897485 ER PT J AU GOLDKLANG, DS AF GOLDKLANG, DS TI RESEARCH WORKSHOP ON METHODOLOGICAL ISSUES IN EVALUATING PREVENTIVE INTERVENTIONS USING MUTUAL SUPPORT SO AMERICAN JOURNAL OF COMMUNITY PSYCHOLOGY LA English DT Article RP GOLDKLANG, DS (reprint author), NIMH,PREVENT RES BRANCH,5600 FISHERS LANE,ROOM 14C-02,ROCKVILLE,MD 20857, USA. NR 10 TC 14 Z9 14 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0091-0562 J9 AM J COMMUN PSYCHOL JI Am. J. Community Psychol. PD OCT PY 1991 VL 19 IS 5 BP 789 EP 795 DI 10.1007/BF00938045 PG 7 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Social Work SC Public, Environmental & Occupational Health; Psychology; Social Work GA GQ062 UT WOS:A1991GQ06200010 PM 1763789 ER PT J AU REICHMAN, ME JUDD, JT LONGCOPE, C SCHATZKIN, A NAIR, PP TAYLOR, PR CAMPBELL, WS SUNKIN, M AF REICHMAN, ME JUDD, JT LONGCOPE, C SCHATZKIN, A NAIR, PP TAYLOR, PR CAMPBELL, WS SUNKIN, M TI ALCOHOL-CONSUMPTION AND HORMONE LEVELS IN A CONTROLLED DIET STUDY OF PREMENOPAUSAL WOMEN SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 1 PY 1991 VL 134 IS 7 BP 715 EP 715 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GN535 UT WOS:A1991GN53500010 ER PT J AU ROWLAND, A BAIRD, D WEINBERG, C SHY, C WILCOX, A AF ROWLAND, A BAIRD, D WEINBERG, C SHY, C WILCOX, A TI REDUCED FERTILITY AMONG DENTAL ASSISTANTS WITH OCCUPATIONAL EXPOSURE TO MERCURY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 1 PY 1991 VL 134 IS 7 BP 723 EP 724 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GN535 UT WOS:A1991GN53500042 ER PT J AU FORMAN, MR YAO, SX GRAUBARD, BI QIAO, YL MCADAMS, M TAYLOR, PR AF FORMAN, MR YAO, SX GRAUBARD, BI QIAO, YL MCADAMS, M TAYLOR, PR TI THE EFFECT OF DIETARY-INTAKE OF FRUITS AND VEGETABLES ON THE ODDS RATIO OF LUNG-CANCER AMONG YUNNAN TIN MINERS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. RI Qiao, You-Lin/B-4139-2012 OI Qiao, You-Lin/0000-0001-6380-0871 NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 1 PY 1991 VL 134 IS 7 BP 725 EP 726 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GN535 UT WOS:A1991GN53500050 ER PT J AU KLEBANOFF, M REGAN, J NUGENT, R AF KLEBANOFF, M REGAN, J NUGENT, R TI MATERNAL GROUP-B STREPTOCOCCAL CARRIAGE AND PREGNANCY OUTCOME SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NICHHD,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 1 PY 1991 VL 134 IS 7 BP 728 EP 728 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GN535 UT WOS:A1991GN53500058 ER PT J AU HILDESHEIM, A WEST, S JONES, C DEVEYRA, E HINUMA, Y AF HILDESHEIM, A WEST, S JONES, C DEVEYRA, E HINUMA, Y TI EPSTEIN-BARR-VIRUS, HERBAL MEDICINE USE, AND RISK OF NASOPHARYNGEAL CARCINOMA SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 1 PY 1991 VL 134 IS 7 BP 758 EP 758 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GN535 UT WOS:A1991GN53500170 ER PT J AU RODRIGUEZ, EM DEMOYA, EA GUERRERO, E MONTERROSO, E PUELLO, E QUINN, TC WEISSENBACHER, M VERMUND, SH AF RODRIGUEZ, EM DEMOYA, EA GUERRERO, E MONTERROSO, E PUELLO, E QUINN, TC WEISSENBACHER, M VERMUND, SH TI HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1), HUMAN T-CELL LYMPHOTROPHIC VIRUS TYPE-I (HTLV-I), SEXUALLY-TRANSMITTED DISEASES, AND GENITAL ULCER DISEASE IN THE DOMINICAN-REPUBLIC SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIAID,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 1 PY 1991 VL 134 IS 7 BP 765 EP 765 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GN535 UT WOS:A1991GN53500196 ER PT J AU BAIRD, D WEINBERG, C VOIGT, L DALING, J AF BAIRD, D WEINBERG, C VOIGT, L DALING, J TI DOUCHING ASSOCIATED WITH SUBFECUNDITY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 1 PY 1991 VL 134 IS 7 BP 770 EP 770 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GN535 UT WOS:A1991GN53500214 ER PT J AU HORNSBY, P WILCOX, A AF HORNSBY, P WILCOX, A TI ONSET OF MENOPAUSE IN WOMEN EXPOSED TO DIETHYLSTILBESTROL INUTERO SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 1 PY 1991 VL 134 IS 7 BP 770 EP 770 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GN535 UT WOS:A1991GN53500215 ER PT J AU CANTOR, KP LYNCH, CF AF CANTOR, KP LYNCH, CF TI PARITY, AGE AT 1ST BIRTH, AND RISK OF BLADDER-CANCER IN IOWA SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 1 PY 1991 VL 134 IS 7 BP 772 EP 772 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GN535 UT WOS:A1991GN53500221 ER PT J AU CHU, KC AF CHU, KC TI CONTROLLING FOR SCREENING BIASES SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 1 PY 1991 VL 134 IS 7 BP 772 EP 772 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GN535 UT WOS:A1991GN53500220 ER PT J AU WEED, D AF WEED, D TI CAUSAL INFERENCE - A MATTER OF PRINCIPLE SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 1 PY 1991 VL 134 IS 7 BP 779 EP 780 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GN535 UT WOS:A1991GN53500251 ER PT J AU BERGASA, NV JONES, EA AF BERGASA, NV JONES, EA TI MANAGEMENT OF THE PRURITUS OF CHOLESTASIS - POTENTIAL ROLE OF OPIATE ANTAGONISTS SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID PRIMARY BILIARY-CIRRHOSIS; BENZODIAZEPINE RECEPTOR LIGANDS; VISUAL ANALOG SCORE; SERUM BILE-ACIDS; HEPATIC-ENCEPHALOPATHY; LIVER-DISEASE; ANIMAL-MODEL; INTRAHEPATIC CHOLESTASIS; EPIDURAL MORPHINE; OPIOID-PEPTIDES RP BERGASA, NV (reprint author), NIDDK,LIVER DIS SECT,BLDG 10,4D52,BETHESDA,MD 20892, USA. NR 96 TC 41 Z9 41 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 1991 VL 86 IS 10 BP 1404 EP 1412 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GJ410 UT WOS:A1991GJ41000003 PM 1928030 ER PT J AU PARKER, RI BARTON, NW READ, EJ BRADY, RO AF PARKER, RI BARTON, NW READ, EJ BRADY, RO TI HEMATOLOGIC IMPROVEMENT IN A PATIENT WITH GAUCHER DISEASE ON LONG-TERM ENZYME REPLACEMENT THERAPY - EVIDENCE FOR DECREASED SPLENIC SEQUESTRATION AND IMPROVED RED-BLOOD-CELL SURVIVAL SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE GAUCHER DISEASE; RBC SURVIVAL; BONE MARROW HISTOPATHOLOGY ID GLUCOCEREBROSIDASE AB We describe here an investigation of the hematologic response of a child with Gaucher disease to a six-year therapeutic trial of human placental mannose-terminated glucocerebrosidase. While on enzyme replacement therapy, the patient's hemoglobin and platelet count significantly increased (6.9 g/dl to 12.2 g/dl, and 39,000/mu-L to 74,000/mu-L, respectively). Over the same time interval his absolute reticulocyte count decreased (88.1 x 10(3)/mu-L to 31.5 x 10(3)/mu-L). The patient's splenic volume decreased by over 60% (2108ml to 797ml) and his bone marrow demonstrated a dramatic clearing of Gaucher cell infiltration. Serum erythropoietin levels were at the lower range of normal at points in time when he was severely anemic and did not change with improvement in hemoglobin. Coincident with the improvement in the patient's hemoglobin, in vivo survival of autologous radiolabeled RBCs increased 34%. The improved hematopoietic profile appeared to result primarily from an increase in the in vivo survival of mature hematopoietic elements secondary to a decrease in splenic sequestration. Improved marrow function secondary to the clearing of Gaucher cell infiltrates may also play a role in his improved hematologic status. C1 NIH,DEPT CLIN PATHOL,HEMATOL SERV,BETHESDA,MD 20892. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NIH,CTR CLIN,BETHESDA,MD 20892. NR 18 TC 32 Z9 33 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD OCT PY 1991 VL 38 IS 2 BP 130 EP 137 DI 10.1002/ajh.2830380211 PG 8 WC Hematology SC Hematology GA GJ125 UT WOS:A1991GJ12500010 PM 1951303 ER PT J AU FRANKENFIELD, DL JOHNSON, RE AF FRANKENFIELD, DL JOHNSON, RE TI REFRACTOMETRY OF CONTROLLED SUBSTANCES SO AMERICAN JOURNAL OF HOSPITAL PHARMACY LA English DT Letter C1 NIDA,ADDICT RES CTR,RES SUPPORT BRANCH,BALTIMORE,MD 21224. RP FRANKENFIELD, DL (reprint author), NIDA,ADDICT RES CTR,PHARM SERV,POB 5180,4940 EASTERN AVE,BLDG C,BALTIMORE,MD 21224, USA. NR 2 TC 4 Z9 4 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 OCT PY 1991 VL 48 IS 10 BP 2129 EP 2130 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GH077 UT WOS:A1991GH07700009 PM 1781464 ER PT J AU GRUNDFAST, K FARRER, L AMOS, J ARNOS, KS ASHER, J BEIGHTON, P DIEHL, S FEX, J FOY, C FRIEDMAN, T GREENBERG, J HOTH, C MILUNSKY, A MORELL, R NANCE, W NEWTON, V RAMESAR, R READ, A SKARE, J SANAGUSTIN, T STEVENS, C WAGNER, R WILCOX, E WINSHIP, I AF GRUNDFAST, K FARRER, L AMOS, J ARNOS, KS ASHER, J BEIGHTON, P DIEHL, S FEX, J FOY, C FRIEDMAN, T GREENBERG, J HOTH, C MILUNSKY, A MORELL, R NANCE, W NEWTON, V RAMESAR, R READ, A SKARE, J SANAGUSTIN, T STEVENS, C WAGNER, R WILCOX, E WINSHIP, I TI WAARDENBURG SYNDROME IS CAUSED BY DEFECTS AT MULTIPLE LOCI, ONE OF WHICH IS TIGHTLY LINKED TO ALPP ON CHROMOSOME-2 - 1ST REPORT OF THE WS CONSORTIUM SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDCD,BETHESDA,MD. BOSTON UNIV,BOSTON,MA 02215. GALLAUDET UNIV,WASHINGTON,DC. MICHIGAN STATE UNIV,E LANSING,MI 48824. UNIV CAPE TOWN,CAPE TOWN,SOUTH AFRICA. UNIV MANCHESTER,MANCHESTER M13 9PL,LANCS,ENGLAND. RI Ramesar, Raj/I-6941-2015 OI Ramesar, Raj/0000-0001-5688-1634 NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 17 EP 17 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30900080 ER PT J AU BEALL, S MCFARLIN, D MCFARLAND, H BIDDISON, W HOOD, L AF BEALL, S MCFARLIN, D MCFARLAND, H BIDDISON, W HOOD, L TI SUSCEPTIBILITY FOR MULTIPLE-SCLEROSIS IS DETERMINED BY INHERITANCE OF A 175 KB REGION OF THE TCR-BETA CHAIN LOCUS IN CONJUNCTION WITH HLA CLASS-II GENES SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 UNIV BRITISH COLUMBIA,DEPT MED,DIV NEUROL,VANCOUVER V6T 1W5,BC,CANADA. NIH,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. CALTECH,DIV BIOL,PASADENA,CA 91125. NR 0 TC 2 Z9 2 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 21 EP 21 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30900098 ER PT J AU ANGUIANO, A AMOS, J OATES, R DEAN, M MAHER, T MILUNSKY, A AF ANGUIANO, A AMOS, J OATES, R DEAN, M MAHER, T MILUNSKY, A TI CYSTIC-FIBROSIS (CF) GENE-MUTATIONS IN MALES WITH CONGENITAL BILATERAL ABSENCE OF THE VAS-DEFERENS (CBAVD) SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 BOSTON UNIV,SCH MED,CTR HUMAN GENET,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DEPT UROL,BOSTON,MA 02118. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 22 EP 22 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30900106 ER PT J AU WISTOW, G AF WISTOW, G TI THE RECRUITMENT OF LENS CRYSTALLINS - NEW FUNCTIONS PRECEDE GENE DUPLICATION SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 34 EP 34 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30900168 ER PT J AU GAHL, WA AF GAHL, WA TI DISORDERS OF LYSOSOMAL MEMBRANE-TRANSPORT SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 58 EP 58 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30900279 ER PT J AU WISEMAN, R COCHRAN, C HEGI, M SODERKVIST, P AF WISEMAN, R COCHRAN, C HEGI, M SODERKVIST, P TI ALLELE LOSS DURING CARCINOGENESIS IN MICE SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. NIEHS,MOLEC TOXICOL LABS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 62 EP 62 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30900305 ER PT J AU BUTLER, JD LEVIN, SW FACCHIANO, A MUKHERJEE, AB AF BUTLER, JD LEVIN, SW FACCHIANO, A MUKHERJEE, AB TI CHARACTERIZATION OF CYSTINE BINDING-PROTEIN OF ESCHERICHIA-COLI SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. NICHHD,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 95 EP 95 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30900446 ER PT J AU SIDRANSKY, E STUBBLEFIELD, B ISUJI, S GINNS, E AF SIDRANSKY, E STUBBLEFIELD, B ISUJI, S GINNS, E TI MUTATION ANALYSIS OF GAUCHER PATIENTS WITH OCULOMOTOR ABNORMALITIES SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 106 EP 106 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30900512 ER PT J AU CHOLERTON, S IDLE, M GONZALEZ, FJ IDLE, JR AF CHOLERTON, S IDLE, M GONZALEZ, FJ IDLE, JR TI A POPULATION-STUDY OF COUMARIN METABOLISM SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 UNIV NEWCASTLE UPON TYNE,DEPT PHARMACOL SCI,PHARMACOGENET RES UNIT,NEWCASTLE TYNE NE1 7RU,TYNE & WEAR,ENGLAND. NIH,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 110 EP 110 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30900539 ER PT J AU BARTON, NW DOPPELT, SI MANKIN, HJ BRADY, RO AF BARTON, NW DOPPELT, SI MANKIN, HJ BRADY, RO TI REVERSAL OF THE CLINICAL MANIFESTATIONS OF GAUCHER DISEASE BY ENZYME REPLACEMENT THERAPY SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 112 EP 112 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30900551 ER PT J AU KONDO, I OKANO, K YONAHA, M GONZALEZ, FJ KANAZAWA, I AF KONDO, I OKANO, K YONAHA, M GONZALEZ, FJ KANAZAWA, I TI POLYMORPHIC CYP2D6 GENOTYPES ASSOCIATED WITH DEFICIENT METABOLISM OF DEBRISOQUINE SPARTEINE IN JAPANESE POPULATION SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 UNIV S AFRICA,DEPT HUMAN ECOL & GENET,PRETORIA,SOUTH AFRICA. UNIV TSUKUBA,DEPT NEUROL,SAKURA,IBARAKI 305,JAPAN. NIH,MOLEC CARTINOGENESIS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 112 EP 112 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30900548 ER PT J AU KALER, SG GAHL, WA AF KALER, SG GAHL, WA TI COPPER BLOTTING IN THE STUDY OF MENKES DISEASE SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 116 EP 116 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30900569 ER PT J AU TOJI, LH KIM, C LATORRE, G MODELO, R AF TOJI, LH KIM, C LATORRE, G MODELO, R TI USE OF DNA FINGERPRINTING IN VERIFICATION OF ORIGIN OF SV40-TRANSFORMED CELL-LINES SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIGMS,CORIELL INST MED RES,HUMAN GENET MUTANT CELL REPOSITORY,CAMDEN,NJ. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 117 EP 117 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30900576 ER PT J AU AMOS, CI SHAW, GL HARTGE, P TUCKER, MA AF AMOS, CI SHAW, GL HARTGE, P TUCKER, MA TI AGE AT ONSET FOR FAMILIAL OVARIAN-CANCER SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. RI Tucker, Margaret/B-4297-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 118 EP 118 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30900580 ER PT J AU BENNETT, WP HOLLSTEIN, MC METCALF, RA WELSH, JA HE, A ZHU, SM RESAU, JH TRUMP, BF MIDGLEY, C LANE, DP HARRIS, CC AF BENNETT, WP HOLLSTEIN, MC METCALF, RA WELSH, JA HE, A ZHU, SM RESAU, JH TRUMP, BF MIDGLEY, C LANE, DP HARRIS, CC TI ANALYSIS OF P53 GENETIC AND PROTEIN ALTERATIONS IN ARCHIVAL CHINESE ESOPHAGEAL CANCER SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. CHINA MED UNIV,SHENYANG,PEOPLES R CHINA. SUN YAT SAN UNIV,CANTON,PEOPLES R CHINA. UNIV MARYLAND,BALTIMORE,MD 21201. UNIV DUNDEE,CANC RES CAMPAIGN LAB,DUNDEE DD1 4HN,SCOTLAND. RI Lane, David/C-4920-2008 NR 0 TC 0 Z9 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 118 EP 118 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30900585 ER PT J AU FALCHETTI, A BALE, A AMOROS, A CICCHI, P BANDINI, S MARX, SJ BRANDI, ML AF FALCHETTI, A BALE, A AMOROS, A CICCHI, P BANDINI, S MARX, SJ BRANDI, ML TI ALLELIC LOSS IN THE MULTIPLE ENDOCRINE NEOPLASIA TYPE-1 (MEN1) REGION OF CHROMOSOME-11 IN UREMIC HYPERPARATHYROIDISM SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 YALE UNIV,SCH MED,NEW HAVEN,CT 06510. UNIV FLORENCE,I-50121 FLORENCE,ITALY. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 120 EP 120 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30900595 ER PT J AU CARTER, CL HU, N WU, M LIN, PZ MURIGANDE, C BONNEY, GE AF CARTER, CL HU, N WU, M LIN, PZ MURIGANDE, C BONNEY, GE TI SEGREGATION ANALYSIS OF ESOPHAGEAL CANCER IN 221 HIGH-RISK CHINESE FAMILIES SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI,DIV CANC PREVENT & CONTROL,ROCKVILLE,MD. CHINESE ACAD MED SCI,INST CANC,BEIJING,PEOPLES R CHINA. HOWARD UNIV,CTR CANC,WASHINGTON,DC 20059. NR 0 TC 0 Z9 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 121 EP 121 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30900601 ER PT J AU LATIF, F TORY, K MODI, W DELISIO, J ORCUTT, ML HAMPSCH, K LINEHAN, M ZBAR, B LERMAN, MI AF LATIF, F TORY, K MODI, W DELISIO, J ORCUTT, ML HAMPSCH, K LINEHAN, M ZBAR, B LERMAN, MI TI NEW RFV MARKER LOCI AROUND THE VON HIPPEL-LINDAU TUMOR SUPPRESSOR GENE LOCUS SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI,FCRDC,IMMUNOBIOL LAB,FREDERICK,MD 21701. PRI DYNCORP,FREDERICK,MD. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 4 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 OCT PY 1991 VL 49 IS 4 SU S BP 121 EP 121 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30900603 ER PT J AU METCALF, RA VAHAKANGAS, K WELSH, JA BENNETT, WP LEHMAN, TA GERWIN, BI GU, JR SAMET, J LINNAINMAA, K MATTSON, K HARRIS, CC AF METCALF, RA VAHAKANGAS, K WELSH, JA BENNETT, WP LEHMAN, TA GERWIN, BI GU, JR SAMET, J LINNAINMAA, K MATTSON, K HARRIS, CC TI P53 AND K-RAS MUTATIONAL SPECTRA IN EPIDEMIOLOGICALLY DIVERSE POPULATIONS OF LUNG-CANCER VICTIMS INCLUDING RADON AND ASBESTOS EXPOSURE AND THE ABSENCE OF SMOKING EXPOSURE SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. SHANGHAI CANC INST,DEPT BIOCHEM & MOLEC BIOL,SHANGHAI,PEOPLES R CHINA. UNIV NEW MEXICO,CTR CANC,ALBUQUERQUE,NM 87131. INST OCCUPAT HLTH,SF-00290 HELSINKI 29,FINLAND. UNIV HELSINKI,DEPT PULM MED,SF-00100 HELSINKI 10,FINLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 122 EP 122 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30900606 ER PT J AU ELDRIDGE, R PARRY, DM KAISERKUPFER, MI AF ELDRIDGE, R PARRY, DM KAISERKUPFER, MI TI NEUROFIBROMATOSIS 2 (NF2) - CLINICAL HETEROGENEITY AND NATURAL-HISTORY BASED ON 39 INDIVIDUALS IN 9 FAMILIES AND 16 SPORADIC CASES SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NINCDS,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. NEI,BETHESDA,MD 20892. NR 0 TC 14 Z9 14 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 133 EP 133 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30900672 ER PT J AU FILLINGKATZ, MR HERSH, JH AHRENS, EM GAMEL, J AF FILLINGKATZ, MR HERSH, JH AHRENS, EM GAMEL, J TI 2 SIBLINGS WITH PSEUDOXANTHOMA ELASTICUM AND NEUROOPHTHALMIC INVOLVEMENT SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 UNIV LOUISVILLE,LOUISVILLE,KY 40292. NATL INST ALCOHOLISM & ALCOHOL ABUSE,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 1 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 OCT PY 1991 VL 49 IS 4 SU S BP 135 EP 135 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30900683 ER PT J AU PARRY, DM KAISERKUPFER, MI ELDRIDGE, R AF PARRY, DM KAISERKUPFER, MI ELDRIDGE, R TI NEUROFIBROMATOSIS-2 (NF2) - LENS FINDINGS IN 40 PATIENTS IN 5 HIGH-RISK GROUPS SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NEI,BETHESDA,MD 20892. NINCDS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 155 EP 155 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30900803 ER PT J AU PARSHAD, R PRICE, F TARONE, R ROBBINS, J SANFORD, K AF PARSHAD, R PRICE, F TARONE, R ROBBINS, J SANFORD, K TI CYTOGENETIC EVIDENCE FOR A CELL-CYCLE-DEPENDENT DNA-REPAIR DEFICIENCY - A POSSIBLE DIAGNOSTIC FEATURE OF ALZHEIMER-DISEASE SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 HOWARD UNIV,WASHINGTON,DC 20059. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 155 EP 155 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30900806 ER PT J AU POWELL, CM SAAL, HM CHANDRA, RS AF POWELL, CM SAAL, HM CHANDRA, RS TI PHEVR SYNDROME - AN AUTOSOMAL RECESSIVE SYNDROME OF PTERYGIA, CONGENITAL HEART ANOMALIES, EAR ANOMALIES, VERTEBRAL DEFECTS AND RADIAL DYSPLASIA SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 CHILDRENS NATL MED CTR,WASHINGTON,DC. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 157 EP 157 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30900817 ER PT J AU ROUSE, B AZEN, C FREIDMAN, E KOCH, R DELACRUZ, F SHIFRIN, H LEVY, H MATALON, R HANLEY, W AF ROUSE, B AZEN, C FREIDMAN, E KOCH, R DELACRUZ, F SHIFRIN, H LEVY, H MATALON, R HANLEY, W TI MATERNAL PHENYLKETONURIA PREGNANCY OUTCOME - MAJOR ANOMALIES AND FACIAL DYSMORPHOLOGY SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 UNIV TEXAS,MED BRANCH,GALVESTON,TX 77550. CHILDRENS HOSP,LOS ANGELES,CA 90027. NICHHD,ROCKVILLE,MD. CHILDRENS HOSP MED CTR,BOSTON,MA 02115. UNIV ILLINOIS,CHICAGO,IL 60680. HOSP SICK CHILDREN,TORONTO M5G 1X8,ONTARIO,CANADA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 160 EP 160 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30900833 ER PT J AU SANFORD, K PRICE, F SCHAPIRO, M TARONE, R RAPOPORT, S PARSHAD, R AF SANFORD, K PRICE, F SCHAPIRO, M TARONE, R RAPOPORT, S PARSHAD, R TI X-RAY-INDUCED CHROMATID DAMAGE IN CELLS FROM DOWN-SYNDROME AND ALZHEIMER-DISEASE PATIENTS IN RELATION TO DNA-REPAIR AND CANCER PRONENESS SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NATL INST AGING,BETHESDA,MD. HOWARD UNIV,WASHINGTON,DC 20059. NR 0 TC 1 Z9 1 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 161 EP 161 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30900843 ER PT J AU MARINI, JC ORRISON, BM LEWIS, MB AF MARINI, JC ORRISON, BM LEWIS, MB TI OSTEOGENESIS IMPERFECTA TYPE IV ASSOCIATED WITH SERINE SUBSTITUTION FOR ALPHA-2(I) GLY 922 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHHD,HUMAN GENET BRANCH,CONNECT TISSUE DISORDERS SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 197 EP 197 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30901052 ER PT J AU MOWREY, PN CHORNEY, MJ LERMAN, MI ZBAR, B LATIF, F ROGAN, PK RAMER, JC LADDA, RL AF MOWREY, PN CHORNEY, MJ LERMAN, MI ZBAR, B LATIF, F ROGAN, PK RAMER, JC LADDA, RL TI FURTHER MOLECULAR ANALYSIS OF THE DELETION 3P25 SYNDROME SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,HERSHEY,PA 17033. NCI,FREDERICK CANC RES FACIL,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 U1 0 U2 4 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 OCT PY 1991 VL 49 IS 4 SU S BP 199 EP 199 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30901064 ER PT J AU ZBAR, B LATIF, F GLENN, G HOSOE, S YAO, M CHOYKE, P LERMAN, M LINEHAN, M AF ZBAR, B LATIF, F GLENN, G HOSOE, S YAO, M CHOYKE, P LERMAN, M LINEHAN, M TI SCREENING FOR VONHIPPEL-LINDAU DISEASE BY DNA-POLYMORPHISM ANALYSIS SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI,FCRDC,IMMUNOBIOL LAB,FREDERICK,MD 21701. NCI,CANC DIAG BRANCH,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. NIH,CTR DIAGNOST RADIOL CLIN,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 208 EP 208 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30901119 ER PT J AU ZHOU, XH ZHAO, SY LI, S AF ZHOU, XH ZHAO, SY LI, S TI MOLECULAR-CLONING OF HUMAN LDH-C4 GENE AND ITS EXPRESSION SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 SHANGHAI MED UNIV,SHANGHAI,PEOPLES R CHINA. FUDAN UNIV,GENET RES INST,SHANGHAI,PEOPLES R CHINA. NIEHS,GENET LAB,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 235 EP 235 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30901284 ER PT J AU MCGAVRAN, L PARKER, NB OLIVERO, OA POIRIER, MC MANCHESTER, DK AF MCGAVRAN, L PARKER, NB OLIVERO, OA POIRIER, MC MANCHESTER, DK TI AN IMMUNOCYTOGENETIC INVITRO MODEL FOR THE DETECTION OF CHRYSENE-DNA ADDUCTS ON HUMAN-CHROMOSOMES SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 CHILDRENS HOSP,DENVER,CO 80218. UNIV COLORADO,HLTH SCI CTR,DENVER,CO 80262. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 245 EP 245 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30901339 ER PT J AU POWELL, CM ELLINGHAM, TJ ROSENBAUM, KN STANLEY, WS AF POWELL, CM ELLINGHAM, TJ ROSENBAUM, KN STANLEY, WS TI UNBALANCED 15-18 TRANSLOCATION IN A PRADER-WILLI PATIENT MOSAIC FOR A NORMAL-CELL LINE SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 CHILDRENS NATL MED CTR,WASHINGTON,DC. NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 261 EP 261 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30901437 ER PT J AU AKSENTIJEVICH, I GRUBERG, L BALOW, JE DEAN, M PRAS, M KASTNER, DL AF AKSENTIJEVICH, I GRUBERG, L BALOW, JE DEAN, M PRAS, M KASTNER, DL TI LINKAGE ANALYSIS IN FAMILIAL MEDITERRANEAN FEVER (FMF) SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAMS,ARTHRITIS & RHEUMATISM BRANCH,BETHESDA,MD. PRI DYNCORP,FREDERICK,MD. HELLER INST MED RES,TEL AVIV,ISRAEL. NR 0 TC 4 Z9 4 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 335 EP 335 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30901869 ER PT J AU BERRETTINI, WH DETERAWADLEIGH, SD GOLDIN, LR MARTINEZ, M HSIEH, WT HOEHE, M ROBB, AS GERSHON, ES AF BERRETTINI, WH DETERAWADLEIGH, SD GOLDIN, LR MARTINEZ, M HSIEH, WT HOEHE, M ROBB, AS GERSHON, ES TI LINKAGE STUDIES OF BIPOLAR ILLNESS SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PSYCHIAT,PHILADELPHIA,PA 19107. NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. RI Martinez, Maria/B-3111-2013 OI Martinez, Maria/0000-0003-2180-4537 NR 0 TC 0 Z9 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 336 EP 336 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30901878 ER PT J AU BOLOS, AM DEAN, M GOLDMAN, D AF BOLOS, AM DEAN, M GOLDMAN, D TI DETECTION OF A DINUCLEOTIDE REPEAT POLYMORPHISM IN THE REGION OF THE 5-HYDROXYTRYPTAMINE 1A (HTR1A) RECEPTOR GENE SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NATL INST ALCOHOL ABUSE & ALCOHOLISM,BETHESDA,MD. PROGRAM RESOURCES INC,FREDERICK,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 336 EP 336 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30901877 ER PT J AU FIBISON, WJ EMANUEL, BS BUETOW, K MCBRIDE, OW AF FIBISON, WJ EMANUEL, BS BUETOW, K MCBRIDE, OW TI ANALYSIS OF INCOMPATIBILITIES WITH H162 (D22S68) IN LINKAGE STUDIES USING CEPH PEDIGREES SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 CHILDRENS HOSP,PHILADELPHIA,PA 19104. NCI,BETHESDA,MD 20892. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. NR 1 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 339 EP 339 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30901898 ER PT J AU GOLDIN, LR AF GOLDIN, LR TI DETECTION OF LINKAGE UNDER HETEROGENEITY - COMPARISON OF THE 2-LOCUS VS ADMIXTURE MODELS SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 340 EP 340 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30901901 ER PT J AU GOLDMAN, D LUCASDERSE, S BOLOS, AM OBRIEN, SJ KIRKNESS, EF FRASER, CM DEAN, M AF GOLDMAN, D LUCASDERSE, S BOLOS, AM OBRIEN, SJ KIRKNESS, EF FRASER, CM DEAN, M TI A TETRANUCLEOTIDE REPEAT POLYMORPHISM AT THE HUMAN BETA-1 GABA RECEPTOR GENE AND MAPPING OF THE GENE TO NEAR THE CENTROMERE OF CHROMOSOME-4 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAAA,BETHESDA,MD. NCI,FREDERICK,MD 21701. PRI DYNCORP,FREDERICK,MD. NR 1 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 340 EP 340 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30901904 ER PT J AU HEITMANCIK, JF TOWBIN, J BRINK, PA HILL, R BRINK, L CZERNUSZEWICA, GZ TAPSCOTT, T TRAKHTENGROIT, A PERRYMAN, MB ROBERTS, R AF HEITMANCIK, JF TOWBIN, J BRINK, PA HILL, R BRINK, L CZERNUSZEWICA, GZ TAPSCOTT, T TRAKHTENGROIT, A PERRYMAN, MB ROBERTS, R TI LOCALIZATION OF THE GENE FOR FAMILIAL HYPERTROPHIC CARDIOMYOPATHY TO CHROMOSOME 14QL IN A DIVERSE AMERICAN POPULATION SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NEI,LMOD,BETHESDA,MD 20892. BAYLOR COLL MED,HOUSTON,TX 77030. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 343 EP 343 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30901917 ER PT J AU KEITH, T GINNS, EI EGELAND, JA FALLS, K ALLEN, C LONG, RT PHIPPS, P GRAVIUS, T OLSSON, K BAILEY, J PAULS, DL PAUL, SM AF KEITH, T GINNS, EI EGELAND, JA FALLS, K ALLEN, C LONG, RT PHIPPS, P GRAVIUS, T OLSSON, K BAILEY, J PAULS, DL PAUL, SM TI SYSTEMATIC SEARCH OF THE GENOME FOR MARKERS LINKED TO BIPOLAR AFFECTIVE-DISORDER SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 COLLABORAT RES INC,BEDFORD,MA. NIMH,BETHESDA,MD 20892. UNIV MIAMI,SCH MED,MIAMI,FL 33152. YALE UNIV,SCH MED,NEW HAVEN,CT 06510. NR 0 TC 1 Z9 1 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 346 EP 346 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30901936 ER PT J AU MARTINEZ, MM DEMENAIS, FM BONNEY, GE AF MARTINEZ, MM DEMENAIS, FM BONNEY, GE TI USE OF THE REGRESSIVE LOGISTIC-MODELS IN LINKAGE ANALYSIS OF COMPLEX DISORDERS SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIMH,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. HOWARD UNIV,CTR CANC,WASHINGTON,DC 20059. RI Demenais, Florence/G-3298-2013; Martinez, Maria/B-3111-2013 OI Demenais, Florence/0000-0001-8361-0936; Martinez, Maria/0000-0003-2180-4537 NR 0 TC 3 Z9 3 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 OCT PY 1991 VL 49 IS 4 SU S BP 350 EP 350 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30901962 ER PT J AU MORETTI, T DEAN, M KOZAK, C OBRIEN, SJ GOLDMAN, D AF MORETTI, T DEAN, M KOZAK, C OBRIEN, SJ GOLDMAN, D TI THE CLASS-III ADH GENE IS LOCATED IN THE ADH GENE-COMPLEX AND MULTIPLE PSEUDOGENES ARE DISPERSED THROUGHOUT THE GENOME SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAAA,BETHESDA,MD. NIAID,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. PROGRAM RESOURCES INC DYN CORP,FREDERICK,MD. NR 0 TC 1 Z9 1 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 351 EP 351 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30901970 ER PT J AU SMITH, RJH DAIGER, SP PELIAS, MZ KIMBERLING, WJ HERRERA, CH HEJTMANCIK, JF AF SMITH, RJH DAIGER, SP PELIAS, MZ KIMBERLING, WJ HERRERA, CH HEJTMANCIK, JF TI LINKAGE ANALYSIS OF USHER SYNDROME IN THE LOUISIANA ACADIAN POPULATION - CLINICAL AND GENETIC-HETEROGENEITY SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NEI,BETHESDA,MD 20892. UNIV IOWA HOSP & CLIN,IOWA CITY,IA 52242. BOYS TOWN NATL RES HOSP,OMAHA,NE. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 360 EP 360 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902022 ER PT J AU XIAO, H MERRIL, CR POLYMEROPOULOS, MH AF XIAO, H MERRIL, CR POLYMEROPOULOS, MH TI INFORMATIVENESS OF TRINUCLEOTIDE AND TETRANUCLEOTIDE REPEAT SEQUENCE POLYMORPHISMS SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIMH,LGB,WASHINGTON,DC 20032. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 364 EP 364 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902047 ER PT J AU MULIVOR, RA GREENE, AE DRWINGA, HL TOJI, LH KIM, C AF MULIVOR, RA GREENE, AE DRWINGA, HL TOJI, LH KIM, C TI CHARACTERIZATION OF DNA FROM SINGLE HUMAN-CHROMOSOME HYBRIDS SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 CORIELL INST MED RES,NIGMS HUMAN GENET MUTANT CELL REPOSITORY,CAMDEN,NJ. NR 0 TC 1 Z9 1 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 370 EP 370 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902078 ER PT J AU ZULLO, S KENNEDY, JL POLYMEROPOLOUS, M GELERNTER, J TALLINI, G KIDD, KK AF ZULLO, S KENNEDY, JL POLYMEROPOLOUS, M GELERNTER, J TALLINI, G KIDD, KK TI MITOCHONDRIAL-DNA CAN BE AN EFFICIENT COMPETITOR IN STS PCR SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,WASHINGTON,DC 20032. YALE UNIV,SCH MED,DEPT HUMAN GENET,NEW HAVEN,CT 06510. YALE UNIV,SCH MED,DEPT PSYCHIAT,NEW HAVEN,CT 06510. YALE UNIV,SCH MED,DEPT PATHOL,NEW HAVEN,CT 06510. VET ADM MED CTR,W HAVEN,CT 06516. NR 0 TC 0 Z9 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 373 EP 373 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902099 ER PT J AU ENCIO, IJ HSIEH, WT BARRICK, J DETERAWADLEIGH, SD AF ENCIO, IJ HSIEH, WT BARRICK, J DETERAWADLEIGH, SD TI CHARACTERIZATION OF THE CPG-RICH ISLAND AND PHYSICAL MAP OF THE HUMAN GLUCOCORTICOID RECEPTOR GENE REGION SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIMH,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 377 EP 377 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902119 ER PT J AU FUTREAL, PA ANNAB, LA WISEMAN, RW BARRETT, JC AF FUTREAL, PA ANNAB, LA WISEMAN, RW BARRETT, JC TI PHYSICAL MAPPING OF A SENESCENCE LOCUS ON HUMAN CHROMOSOME-1Q SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. NR 0 TC 1 Z9 1 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 OCT PY 1991 VL 49 IS 4 SU S BP 378 EP 378 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902130 ER PT J AU LATIF, F MODI, W HEPPELPORTAN, A DELISIO, J ORCUTT, ML KAMPSCH, K TORY, K RABBITTS, PH ZHAR, B LERMAN, MI AF LATIF, F MODI, W HEPPELPORTAN, A DELISIO, J ORCUTT, ML KAMPSCH, K TORY, K RABBITTS, PH ZHAR, B LERMAN, MI TI 10-NEW LANDMARK RFV MARKER LOCI ON CHROMOSOME-3P ORDERED BY FLUORESCENT INSITU HYBRIDIZATION AND GENETIC-MAPPING SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI,FCRDC,IMMUNOBIOL LAB,FREDERICK,MD 21701. DYNCORP,PRI,FREDERICK,MD. MRC,CAMBRIDGE CB2 2QH,ENGLAND. NR 0 TC 0 Z9 0 U1 0 U2 4 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 OCT PY 1991 VL 49 IS 4 SU S BP 383 EP 383 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902156 ER PT J AU MARES, A LEDBETTER, DH LEDBETTER, SA PERRYMAN, MB DONISKELLER, H ROBERTS, R HEJTMANCIK, JF AF MARES, A LEDBETTER, DH LEDBETTER, SA PERRYMAN, MB DONISKELLER, H ROBERTS, R HEJTMANCIK, JF TI RADIATION HYBRIDS FROM CHROMOSOME-14 - IRS-PCR CHARACTERIZATION AND INITIAL MAPPING STUDIES SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 BAYLOR COLL MED,HOUSTON,TX 77030. WASHINGTON UNIV,SCH MED,ST LOUIS,MO 63110. NEI,LMOD,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 384 EP 384 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902161 ER PT J AU POLYMEROPOULOS, MH HONG, XG GLODEK, A GORSKI, M ADAMS, MD MORENO, RF FITZGERALD, MG VENTER, JC MERRIL, CR AF POLYMEROPOULOS, MH HONG, XG GLODEK, A GORSKI, M ADAMS, MD MORENO, RF FITZGERALD, MG VENTER, JC MERRIL, CR TI CHROMOSOMAL LOCALIZATION OF 60 BRAIN CDNAS SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIMH,LBG,WASHINGTON,DC 20032. NINCDS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 386 EP 386 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902174 ER PT J AU BRAY, P LICHTER, P RIED, T WARD, D DAWID, I AF BRAY, P LICHTER, P RIED, T WARD, D DAWID, I TI ANALYSIS OF HUMAN ZINC FINGER GENES SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. GERMAN CANC RES CTR,INST VIRUSFORSCH,W-6900 HEIDELBERG 1,GERMANY. YALE UNIV,SCH MED,NEW HAVEN,CT 06510. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 400 EP 400 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902257 ER PT J AU BURNS, AL SHIRVAN, A MCBRIDE, OW SRIVASTAVA, M POLLARD, HB AF BURNS, AL SHIRVAN, A MCBRIDE, OW SRIVASTAVA, M POLLARD, HB TI ORGANIZATION AND LOCALIZATION OF THE HUMAN SYNEXIN (ANNEXIN VII) GENE SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIADDKD,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 1 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 OCT PY 1991 VL 49 IS 4 SU S BP 401 EP 401 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902264 ER PT J AU CHAMBERS, C RUSSELL, P AF CHAMBERS, C RUSSELL, P TI DELETION MUTATION IN AN EYE LENS SPECIFIC PROTEIN - AN ANIMAL-MODEL FOR INHERITED CATARACTS SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NEI,MECH OCULAR DIS LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 401 EP 401 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902265 ER PT J AU CUTTING, GR OHARA, BF GUGGINO, WB UHL, GR AF CUTTING, GR OHARA, BF GUGGINO, WB UHL, GR TI IDENTIFICATION OF 2 MEMBERS OF A NOVEL GABA SUBUNIT CLASS HIGHLY EXPRESSED IN THE HUMAN RETINA SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDA,MOLEC NEUROBIOL LAB,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. NR 0 TC 1 Z9 1 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 OCT PY 1991 VL 49 IS 4 SU S BP 402 EP 402 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902268 ER PT J AU ECCLES, M WALLIS, L FIDLER, A SPURR, N GOODFELLOW, P DRESSLER, G REEVE, A AF ECCLES, M WALLIS, L FIDLER, A SPURR, N GOODFELLOW, P DRESSLER, G REEVE, A TI CLONING AND CHROMOSOMAL LOCALIZATION OF HUMAN PAX2 GENE TO 10Q22.1-Q24.3 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 ICRE,CLARE HALL LABS,HERTFORD EN6 3LD,ENGLAND. UNIV OTAGO,DEPT BIOCHEM,DUNEDIN,NEW ZEALAND. UNIV BRITISH COLUMBIA,DEPT MED GENET,VANCOUVER V6T 1W5,BC,CANADA. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 403 EP 403 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902278 ER PT J AU HUANG, SZ ZENG, FY RODGERS, GP SCHECHTER, AN REN, ZR ZENG, YT AF HUANG, SZ ZENG, FY RODGERS, GP SCHECHTER, AN REN, ZR ZENG, YT TI A NEW APPROACH TO THE INVESTIGATION OF RNA SPLICING DEFECT IN BETA-THAL GENE - DIRECT SEQUENCING OF THE PCR AMPLIFIED CDNAS SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 SHANGHAI CHILDRENS HOSP,SHANGHAI INST MED GENET,SHANGHAI,PEOPLES R CHINA. NIDDK,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 407 EP 407 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902299 ER PT J AU LAUBACH, V HILDESHEIM, J RYAN, WJ BRANTLY, M AF LAUBACH, V HILDESHEIM, J RYAN, WJ BRANTLY, M TI ALPHA-1-ANTITRYPSIN NULLWEST - ABSENCE OF DETECTABLE SERUM ALPHA-1-ANTITRYPSIN AS A RESULT OF A POINT MUTATION IN A MESSENGER-RNA SPLICE DONOR SITE SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHHD,HUMAN GENET BRANCH,BETHESDA,MD. RHD HOSP,DALLAS,TX. RI Laubach, Victor/E-8818-2015 OI Laubach, Victor/0000-0001-9673-5383 NR 0 TC 0 Z9 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 411 EP 411 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902324 ER PT J AU SHARIEF, FS LI, SSL AF SHARIEF, FS LI, SSL TI MOLECULAR CHARACTERIZATION OF HUMAN PROSTATIC ACID-PHOSPHATASE GENE SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIEHS,GENET LAB,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 412 EP 412 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902327 ER PT J AU ROMAN, DG DANCIS, A ANDERSON, GJ KLAUSNER, RD AF ROMAN, DG DANCIS, A ANDERSON, GJ KLAUSNER, RD TI CLONING OF THE FERRIC REDUCTASE GENE OF THE YEAST SAHIZOSACCHAROMYCES-POMBE - IMPLICATIONS FOR HUMAN IRON-METABOLISM SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. RI Anderson, Gregory/G-4148-2013 OI Anderson, Gregory/0000-0002-8814-5866 NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 417 EP 417 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902358 ER PT J AU WOOD, CM WHITE, JJ STEWART, DA NUELL, MJ LEDBETTER, DH EDDY, RL SHOWS, TB MORTON, CC DANNER, DB AF WOOD, CM WHITE, JJ STEWART, DA NUELL, MJ LEDBETTER, DH EDDY, RL SHOWS, TB MORTON, CC DANNER, DB TI A NOVEL INTRACELLULAR ANTIPROLIFERATIVE PROTEIN, PROHIBITION, IS THE MAMMALIAN EQUIVALENT OF THE DROSOPHILA-MELANOGASTER GENE PRODUCT-CC ESSENTIAL FOR DEVELOPMENT SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIA,MOLEC GENET LAB,BALTIMORE,MD 21224. BAYLOR COLL MED,INST MOLEC GENET,HOUSTON,TX 77030. ROSWELL PK CANC INST,DEPT HUMAN GENET,BUFFALO,TX. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 423 EP 423 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902397 ER PT J AU ASHIZAWA, T DUNNE, CJ DUBEL, JR PERRYMAN, MB ROBERTS, R HEJTMANCIK, JF AF ASHIZAWA, T DUNNE, CJ DUBEL, JR PERRYMAN, MB ROBERTS, R HEJTMANCIK, JF TI ANTICIPATION IN MYOTONIC-DYSTROPHY SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 BAYLOR COLL MED,HOUSTON,TX 77030. NEI,LMOD,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 2 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 OCT PY 1991 VL 49 IS 4 SU S BP 424 EP 424 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902403 ER PT J AU DEAN, M WHITE, M GERRARD, B STEWART, C THOMAS, K HAZEL, M CAPECCHI, M AF DEAN, M WHITE, M GERRARD, B STEWART, C THOMAS, K HAZEL, M CAPECCHI, M TI PROBING THE FUNCTION OF THE CYSTIC-FIBROSIS GENE SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 PRI DYNCORP,FREDERICK,MD. NCI,FREDERICK,MD 21701. UNIV UTAH,SALT LAKE CITY,UT 84112. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 0 TC 0 Z9 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 426 EP 426 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902412 ER PT J AU KULKARNI, AB BECKER, D GEISER, A KARLSSON, S AF KULKARNI, AB BECKER, D GEISER, A KARLSSON, S TI TARGETED DISRUPTION OF THE TRANSFORMING GROWTH FACTOR-B1 (TGF-B1) GENE IN EMBRYONIC STEM (ES) CELLS SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NINCDS,DMNB,MOLEC & MED GENET SECT,BETHESDA,MD 20892. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 429 EP 429 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902432 ER PT J AU NIELSEN, DA BLUME, JE SHAPIRO, DJ AF NIELSEN, DA BLUME, JE SHAPIRO, DJ TI A NOVEL, CONSERVED MESSENGER-RNA SEQUENCE WHICH PARTICIPATES IN THE PROPER FORMATION OF 3' MESSENGER-RNA ENDS SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAAA,CLIN STUDIES LAB,BETHESDA,MD. ROCHE INST MOLEC BIOL,NUTLEY,NJ 07110. UNIV ILLINOIS,DEPT BIOCHEM,URBANA,IL 61801. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 431 EP 431 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902443 ER PT J AU SWERGOLD, GD SINGER, MF AF SWERGOLD, GD SINGER, MF TI THE HUMAN LINE-1 (L1HS) ELEMENT - IDENTIFICATION AND ANALYSIS OF ITS INTERNAL PROMOTER SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 433 EP 433 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902454 ER PT J AU MCKINNEY, CE MARTIN, BM MILES, R GINNS, EI AF MCKINNEY, CE MARTIN, BM MILES, R GINNS, EI TI POTENTIAL OF ENZYME REPLACEMENT THERAPY FOR GAUCHER DISEASE USING RECOMBINANT HUMAN GLUCOCEREBROSIDASE IN HEPATOCYTES SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIMH,STAT BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 437 EP 437 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902480 ER PT J AU SHAFER, GE EMERY, DW KARSON, EM SACHS, DH LEGUERN, C AF SHAFER, GE EMERY, DW KARSON, EM SACHS, DH LEGUERN, C TI EXPRESSION OF ALLOGENEIC SWINE CLASS-II GENES IN BONE-MARROW CELLS USING RECOMBINANT RETROVIRAL VECTORS SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 438 EP 438 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902484 ER PT J AU GALLAGHER, JE INMON, J JACKSON, M GEORGE, M BELL, DA DEMARINI, DM AF GALLAGHER, JE INMON, J JACKSON, M GEORGE, M BELL, DA DEMARINI, DM TI HIGH-YIELD OF DNA ISOLATED FROM HUMAN HAIR SHAFTS SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 US EPA,INST GENET TOXICOL,RES TRIANGLE PK,NC 27711. EHRT,DURHAM,NC. NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 440 EP 440 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902497 ER PT J AU TYBULEWICZ, V TREMBLAY, ML LAMARCA, ME STUBBLEFIELD, BK WINFIELD, S ZABLOCKA, B SIDRANSKY, E MARTIN, BM WESTPHAL, H MULLIGAN, RC GINNS, EI AF TYBULEWICZ, V TREMBLAY, ML LAMARCA, ME STUBBLEFIELD, BK WINFIELD, S ZABLOCKA, B SIDRANSKY, E MARTIN, BM WESTPHAL, H MULLIGAN, RC GINNS, EI TI GENERATION OF CHIMERIC MICE WITH GLUCOCEREBROSIDASE GENE-MUTATIONS INTRODUCED BY TARGETED HOMOLOGOUS RECOMBINATION IN EMBRYONIC STEM-CELLS TO PRODUCE A MOUSE MODEL OF GAUCHER DISEASE SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA. MIT,DEPT BIOL,CAMBRIDGE,MA 02139. NICHHD,MAM GENES DEV,BETHESDA,MD. NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NR 0 TC 5 Z9 5 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 441 EP 441 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902499 ER PT J AU MICHAUD, J BRODY, L FONTAINE, G ROBERT, MF STEEL, G KAISERKUPFER, M MITCHELL, G VALLE, D AF MICHAUD, J BRODY, L FONTAINE, G ROBERT, MF STEEL, G KAISERKUPFER, M MITCHELL, G VALLE, D TI STRAND-SEPARATION GEL-ELECTROPHORESIS (SSGE) - PROSPECTIVE-STUDY OF MUTATION DETECTION IN THE ORNITHINE-DELTA-AMINOTRANSFERASE (OAT) GENE OF PATIENTS WITH GYRATE ATROPHY OF THE CHOROID AND RETINA (GA) SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 HOP ST JUSTINE,MONTREAL H3T 1C5,QUEBEC,CANADA. NEI,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,HOWARD HUGHES MED INST,BALTIMORE,MD 21218. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 443 EP 443 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902513 ER PT J AU SAPERSTEIN, DA SI, JS CHADER, GJ NICKERSON, JM AF SAPERSTEIN, DA SI, JS CHADER, GJ NICKERSON, JM TI A CANDIDATE GENE ANALYSIS OF FUNDUS-ALBIPUNCTATUS UTILIZING POLYMERASE CHAIN-REACTION COUPLED RESTRICTION DIGESTS SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NEI,LRCMB,BETHESDA,MD 20892. BETHESDA EYE INST,ST LOUIS,MO 63110. NR 0 TC 0 Z9 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 444 EP 444 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902518 ER PT J AU JONES, IM BURKHARTSCHULTZ, K STROUT, CL THOMPSON, C AF JONES, IM BURKHARTSCHULTZ, K STROUT, CL THOMPSON, C TI SOMATIC MUTAGENESIS - SEQUENCE-ANALYSIS OF THE HPRT GENE IN MUTANT HUMAN-LYMPHOCYTES SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 LAWRENCE LIVERMORE NATL LAB,LIVERMORE,CA 94550. NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 448 EP 448 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902546 ER PT J AU VANDERHOUT, AH VANDERVLIES, P WIJMENGA, C OOSTERHUIS, JW LI, FP BUYS, CHCM AF VANDERHOUT, AH VANDERVLIES, P WIJMENGA, C OOSTERHUIS, JW LI, FP BUYS, CHCM TI DELIMITATION OF THE REGION OF COMMON ALLELIC LOSSES ON 3P IN SPORADIC RENAL-CELL CARCINOMA SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 UNIV GRONINGEN,DEPT MED GENET,9700 AB GRONINGEN,NETHERLANDS. UNIV GRONINGEN,DEPT PATHOL,9700 AB GRONINGEN,NETHERLANDS. NCI,BOSTON,MA. RI Wijmenga, Cisca/D-2173-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 458 EP 458 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902604 ER PT J AU KITTUR, S SCHOONMAKER, M MULLER, D ANDRES, R ADLER, W AF KITTUR, S SCHOONMAKER, M MULLER, D ANDRES, R ADLER, W TI APOLIPOPROTEIN C-2 POLYMORPHISM IN AGING SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIA,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 473 EP 473 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902692 ER PT J AU KNIGHT, R PARSHAD, R PRICE, F SANFORD, K AF KNIGHT, R PARSHAD, R PRICE, F SANFORD, K TI CYTOGENETIC RESPONSE OF BLOOD-LYMPHOCYTES TO G2 PHASE X-IRRADIATION IN RELATION TO FAMILY HISTORY OF CANCER SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. HOWARD UNIV,WASHINGTON,DC 20059. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 473 EP 473 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902690 ER PT J AU DAY, CE ZHAO, TM ROBINSON, MA AF DAY, CE ZHAO, TM ROBINSON, MA TI RAPID SCREENING FOR CODING REGION SUBSTITUTIONS IN T-CELL RECEPTOR GENES SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAID,IMMUNOGENET LAB,ROCKVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 1991 VL 49 IS 4 SU S BP 488 EP 488 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA GR309 UT WOS:A1991GR30902782 ER PT J AU HAYES, RB HERRICK, RF MAHAR, H BLAIR, A STEWART, PA AF HAYES, RB HERRICK, RF MAHAR, H BLAIR, A STEWART, PA TI MORTALITY OF UNITED-STATES EMBALMERS AND FUNERAL DIRECTORS - REPLY SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Letter DE EMBALMER EXPOSURES; FORMALDEHYDE; KIDNEY DISEASE C1 NIOSH,CINCINNATI,OH 45226. NIH,BETHESDA,MD 20892. RP HAYES, RB (reprint author), NCI,BETHESDA,MD 20892, USA. NR 7 TC 1 Z9 1 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 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD OCT PY 1991 VL 20 IS 4 BP 569 EP 570 DI 10.1002/ajim.4700200412 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GG480 UT WOS:A1991GG48000011 ER PT J AU MERINO, MJ AF MERINO, MJ TI VAGINAL-CANCER - THE ROLE OF INFECTIOUS AND ENVIRONMENTAL-FACTORS SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT CONF ON VULVOVAGINITIS : CAUSES AND THERAPIES CY FEB 04-05, 1991 CL BETHESDA, MD SP NIH, NICHHD, INT SOC STUDY VULVAR DIS, ORTHO PHARM DE VAGINAL CANCER; HERPES SIMPLEX VIRUS; HUMAN PAPILLOMAVIRUS; DIETHYLSTILBESTROL; CERVICAL CANCER ID HUMAN PAPILLOMAVIRUS INFECTION; HERPES-SIMPLEX VIRUS; CLEAR-CELL ADENOCARCINOMA; CERVICAL-CANCER; UTERINE CERVIX; CARCINOMA; NEOPLASIA; HYSTERECTOMY; MALIGNANCIES; IRRADIATION AB Primary cancers of the vagina are rare. They comprise 1% to 2% of all gynecologic malignancies and occur predominantly in older women. The diagnosis of primary carcinoma of the vagina requires that the cervix and vulva be intact and that no clinical evidence of other primary tumors exist. Approximately 90% of all vaginal tumors are squamous cell in type on histologic examination. Adenocarcinoma, which is much less common (2% to 4%), is seen primarily in younger women with in utero exposure to diethylstilbestrol, In addition to exposure to diethylstilbestrol, other environmental factors have been associated with the development of vaginal tumors, including chronic irritation from pessaries, previous hysterectomy for benign disease, immunosuppression therapy, cervical irradiation, and endometriosis. Infectious causes seem to play an even more pernicious role in vaginal cancer. The two agents most often implicated are herpes simplex virus and human papillomavirus. These viruses appear to serve as cofactors in the inducement of various genital cancers, working together or with environmental agents such as diethylstilbestrol and host-related genetic abnormalities. The prognosis of vaginal cancer depends on the stage of the disease, with an overall 5-year survival rate of 80% to 90% for early stages. RP MERINO, MJ (reprint author), NCI,PATHOL LAB,BLDG 10,RM 2N-212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 37 TC 35 Z9 35 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 OCT PY 1991 VL 165 IS 4 SU S BP 1255 EP 1262 PN 2 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA GN596 UT WOS:A1991GN59600017 PM 1659200 ER PT J AU ENOMOTO, T WEGHORST, CM INOUE, M TANIZAWA, O RICE, JM AF ENOMOTO, T WEGHORST, CM INOUE, M TANIZAWA, O RICE, JM TI K-RAS ACTIVATION OCCURS FREQUENTLY IN MUCINOUS ADENOCARCINOMAS AND RARELY IN OTHER COMMON EPITHELIAL TUMORS OF THE HUMAN OVARY SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; GENE-MUTATIONS; ONCOGENE; CANCER; TUMORIGENESIS; CARCINOMAS; HER-2/NEU; DNA AB To explore the role of mutational activation of members of the ras family of cellular protooncogenes in the development of human ovarian neoplasms, a series of 37 ovarian tumors from Japanese patients was studied. These included 30 common epithelial tumors (1 mucinous tumor of borderline malignancy, 7 mucinous adenocarcinomas, and 22 nonmucinous carcinomas: 10 serous, 3 clear cell, 8 endometrioid, and 1 undifferentiated), 5 tumors of germ cell origin, and 2 sex cord/stromal cell tumors. Polymerase chain reaction was performed from selected areas of deparaffinized sections of formalin-fixed paraffin-embedded tissue, and the presence of activating point mutations in codons 12, 13, and 61 of the H-, N-, and K-ras genes was probed by dot-blot hybridization analysis with mutation specific oligonucleotides. Mutations in K-ras were also looked for by direct genomic sequencing. The overall frequency of ras gene mutations was 10/37 (27%). Mutations were detected only in K-ras, and were found in most of the mucinous tumors, including the one such tumor of borderline malignancy (6/8; 75%). In one mucinous adenocarcinoma, two mutations were detected in paraffin-embedded material that had not previously been found in high molecular weight DNA isolated from frozen tissue from the same case. K-ras mutations occurred significantly more frequently in mucinous tumors (6/8, 75%) than in serous carcinomas (2/10, 20%; P = 0.031) or in all nonmucinous types of epithelial ovarian tumors combined (3/22, 14%; P = 0.0031). C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21701. OSAKA UNIV,SCH MED,DEPT OBSTET & GYNECOL,OSAKA,JAPAN. NR 35 TC 165 Z9 169 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 OCT PY 1991 VL 139 IS 4 BP 777 EP 785 PG 9 WC Pathology SC Pathology GA GK413 UT WOS:A1991GK41300011 PM 1656759 ER PT J AU MORGAN, HE SMIRNOV, V HURD, SS TKACHUK, V AF MORGAN, HE SMIRNOV, V HURD, SS TKACHUK, V TI CARDIOVASCULAR AND PULMONARY BIOLOGY AND MEDICINE UNITED-STATES-USSR JOINT SYMPOSIUM - SEPTEMBER 18-20, 1990, SUZDAL, USSR - INTRODUCTION SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Editorial Material C1 ACAD MED SCI USSR,INST EXPTL CARDIOL,MOSCOW 109801,USSR. ACAD MED SCI USSR,CARDIOL RES INST,MOSCOW 109801,USSR. NHLBI,DIV LUNG DIS,BETHESDA,MD 20892. ACAD MED SCI USSR,DEPT BIOCHEM,MOSCOW 109801,USSR. RP MORGAN, HE (reprint author), GEISINGER MED CLIN,RES,DANVILLE,PA 17822, USA. NR 0 TC 0 Z9 0 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 OCT PY 1991 VL 261 IS 4 SU S BP 1 EP 1 PG 1 WC Physiology SC Physiology GA GL126 UT WOS:A1991GL12600001 ER PT J AU FRALIX, TA HEINEMAN, FW BALABAN, RS AF FRALIX, TA HEINEMAN, FW BALABAN, RS TI EFFECT OF WORK ON INTRACELLULAR CALCIUM OF THE INTACT HEART SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article; Proceedings Paper CT US-USSR JOINT SYMP ON CARDIOVASCULAR AND PULMONARY BIOLOGY AND MEDICINE CY SEP 18-20, 1990 CL SUZDAL, USSR DE OXYGEN CONSUMPTION; INDO-1; FLUORESCENCE; RABBIT; AFTERLOAD; ISOPROTERENOL ID PERFUSED RAT-HEART; OXIDATIVE-PHOSPHORYLATION; DEHYDROGENASE-ACTIVITY; MAMMALIAN HEART; OXYGEN-CONSUMPTION; ENDOTHELIAL-CELLS; INOTROPIC AGENTS; RABBIT HEARTS; RUTHENIUM RED; FLUORESCENCE AB Intracellular calcium has been proposed to play a key role in the orchestration of metabolic rate with contractile activity in the mammalian heart. Calcium is believed to accomplish this task by modulating the contractile apparatus as well as the metabolic process directly, and perhaps simultaneously, during alterations in cardiac work. The purpose of this study was to evaluate whether appropriate changes in intracellular calcium accompany alterations in cardiac work in the intact working rabbit heart. A range of myocardial oxygen consumption was obtained from 0.94 to 6.51-mu-mol.g LV wt-1.min-1 by changing afterload or beta-agonist addition. With the increase in work and associated increase in respiration, an increase in intracellular calcium was observed, on the basis of indo-1 fluorescence. These results indicate that intracellular calcium is a valid candidate as a cytosolic transducer contributing to the orchestration of myofibril adenosinetriphosphatase activity and oxidative phosphorylation in the intact heart. RP FRALIX, TA (reprint author), NHLBI,CARDIAC ENERGET LAB,BETHESDA,MD 20892, USA. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 29 TC 14 Z9 15 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 OCT PY 1991 VL 261 IS 4 SU S BP 54 EP 59 PG 6 WC Physiology SC Physiology GA GL126 UT WOS:A1991GL12600011 PM 1928454 ER PT J AU GLUKHOVA, MA SHEKHONIN, BV KRUTH, H KOTELIANSKY, VE AF GLUKHOVA, MA SHEKHONIN, BV KRUTH, H KOTELIANSKY, VE TI EXPRESSION OF CYTOKERATIN-8 IN HUMAN AORTIC SMOOTH-MUSCLE CELLS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article; Proceedings Paper CT US-USSR JOINT SYMP ON CARDIOVASCULAR AND PULMONARY BIOLOGY AND MEDICINE CY SEP 18-20, 1990 CL SUZDAL, USSR DE CYTODIFFERENTIATION; FETAL PHENOTYPE; LIPID ACCUMULATION ID HUMAN ATHEROSCLEROTIC LESIONS; CYTOSKELETAL PROTEINS; DESMIN; GENE; COEXPRESSION; FILAMENTS; VIMENTIN; VARIANTS; PLAQUES; TUMORS AB An immunofluorescence method was used to study the expression of cytokeratin 8 in human aortic smooth muscle cells (SMCs) during prenatal development and in atherosclerotic plaques. Aortic SMCs from a 10-wk-old fetus contained cytokeratin 8 in additional to vimentin and a small amount of desmin, whereas, in the cells from a 25-wk-old fetus, cytokeratin 8 was not detected. Cytokeratin 8 was found in the SMCs from intimal thickenings, fatty streaks, and atherosclerotic fibrous plaques. Clusters of cytokeratin 8-positive cells were more abundant in rather advanced lesions (fibrous plaques) that contained at least some amount of lipid. Expression of cytokeratin 8 in the cells of human atherosclerotic lesions probably reflects general rearrangement of gene expression in the intimal cells. C1 NHLBI,BETHESDA,MD 20892. RP GLUKHOVA, MA (reprint author), USSR CARDIOL RES CTR,INST EXPTL CARDIOL,MOSCOW 121552,USSR. NR 25 TC 20 Z9 20 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD OCT PY 1991 VL 261 IS 4 SU S BP 72 EP 77 PG 6 WC Physiology SC Physiology GA GL126 UT WOS:A1991GL12600014 PM 1718173 ER PT J AU ANDROS, G WOLLMAN, SH AF ANDROS, G WOLLMAN, SH TI KINETICS OF EQUILIBRATION OF RADIOIODIDE IN INDIVIDUAL MOUSE THYROID-FOLLICLES INVIVO SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE QUANTITATIVE AUTORADIOGRAPHY; RATE CONSTANTS; RADIOIODIDE TRANSPORT; THIOURACIL; FOLLICULAR LUMENS; IODINATION INHIBITED ID EPITHELIAL-CELL; C3H MOUSE AB Microdensitometric measurements were made on autoradiographs of radioiodide localized in mouse thyroids subjected to various degrees of stimulation, in which the formation of organic radioiodide was acutely blocked. Estimates were made of the relative concentrations of radioiodide in lumens and cells of follicles and in the nearby blood vessels. Simple models were introduced to interpret the data. Analysis of the ratio of radioiodide concentrations in the lumen and cells of follicles as a function of follicle size and time after injection indicated that smaller follicles equilibrated faster than larger follicles, that the equilibration was faster the more active the gland was, and that the release of radioiodide from follicles in the less active glands must be characterized by a time-dependent exit rate constant. Analysis of the relative concentration of luminal radioiodide as a function of follicle size at short time intervals and in the steady state indicated that the transport properties of the average epithelial cell were generally independent of follicle size. C1 NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 31 TC 1 Z9 1 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 OCT PY 1991 VL 261 IS 4 BP E529 EP E538 PN 1 PG 10 WC Physiology SC Physiology GA GK867 UT WOS:A1991GK86700038 PM 1928343 ER PT J AU KATZ, A SPENCER, MK LILLIOJA, S YAN, Z MOTT, DM HALLER, RG LEWIS, SF AF KATZ, A SPENCER, MK LILLIOJA, S YAN, Z MOTT, DM HALLER, RG LEWIS, SF TI BASAL AND INSULIN-MEDIATED CARBOHYDRATE-METABOLISM IN HUMAN MUSCLE DEFICIENT IN PHOSPHOFRUCTOKINASE-1 SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE TRICARBOXYLIC ACID CYCLE INTERMEDIATES; GLYCOGEN; HEXOSE MONOPHOSPHATES; FRUCTOSE 2,6-BISPHOSPHATE; GLUCOSE 1,6-BISPHOSPHATE; HIGH-ENERGY PHOSPHATES; GLYCOGEN SYNTHASE; GLYCOGEN PHOSPHORYLASE; GLYCOGEN SYNTHASE PHOSPHATASE; EUGLYCEMIC HYPERINSULINEMIA ID HUMAN SKELETAL-MUSCLE; EUGLYCEMIC HYPERINSULINEMIA; GLUCOSE-METABOLISM; GLYCOGEN-SYNTHASE; CYCLE; CONTRACTION; EXERCISE AB Biopsies were obtained from the quadriceps femoris muscle of two male patients deficient in phosphofructokinase (PFK) 1. In the basal state the patients had markedly higher contents of UDP-glucose (approximately 5-fold), hexose monophosphates (approximately 7 - to 13-fold), inosine monophosphate (IMP) (approximately 15-fold), and fructose 2,6-bisphosphate (F-2,6-P2; approximately 6-fold) than controls. Fructose 1,6-bisphosphate was not detectable, and phosphocreatine was lower (33 and 54 mmol/kg dry wt) than in controls [72 +/- 4 (SD)]. Patients had normal fasting plasma glucose and insulin levels and basal glucose turnover rates and responded normally to a 75-g oral glucose challenge. Patients were also studied during euglycemic hyperinsulinemia (approximately 95 mg/dl; 40 and 400 mU.m-2.min-1). Whole body glucose disposal rates were normal during both insulin infusion rates. Biopsies taken after the 400 mU insulin infusion showed decreases in acetylcarnitine and citrate and increases in the fractional activity of glycogen synthase. It is suggested that the high basal levels of F-2,6-P2 are, at least partly, a consequence of the high levels of fructose 6-phosphate, which will stimulate flux through PFK-2 and inhibit fructose-2,6-bisphosphatase. The low phosphocreatine and high IMP contents indicate that carbohydrate availability is important for control of high-energy phosphate metabolism, even in the basal state. The insulin-mediated decreases in acetylcarnitine and citrate suggest an activation of the tricarboxylic acid cycle in skeletal muscle but an absence of the normal response to replenish these intermediates. C1 UNIV ILLINOIS,DEPT KINESIOL,URBANA,IL 61801. NIDDKD,CLIN DIABET & NUTR SECT,PHOENIX,AZ 85016. VET ADM MED CTR,DALLAS,TX 75216. UNIV TEXAS,HLTH SCI CTR,DEPT PHYSIOL,DALLAS,TX 75235. UNIV TEXAS,HLTH SCI CTR,DEPT NEUROL,DALLAS,TX 75235. RI Lillioja, Stephen/A-8185-2012 FU NHLBI NIH HHS [HL-01581, HL-06296] NR 33 TC 5 Z9 5 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD OCT PY 1991 VL 261 IS 4 BP E473 EP E478 PN 1 PG 6 WC Physiology SC Physiology GA GK867 UT WOS:A1991GK86700030 PM 1833982 ER PT J AU WEEKS, BS KOPP, JB HORIKOSHI, S CANNON, FB GARRETT, M KLEINMAN, HK KLOTMAN, PE AF WEEKS, BS KOPP, JB HORIKOSHI, S CANNON, FB GARRETT, M KLEINMAN, HK KLOTMAN, PE TI ADULT AND FETAL HUMAN MESANGIAL CELLS INTERACT WITH SPECIFIC LAMININ DOMAINS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE EXTRACELLULAR MATRIX; BASEMENT MEMBRANES; RECEPTORS ID BASEMENT-MEMBRANES; SYNTHETIC PEPTIDE; A-CHAIN; RECEPTOR; BINDING; PROTEIN; GLYCOPROTEIN; ADHESION; RAT; LOCALIZATION AB Mesangial cells are centrally located pericytes in the renal glomerulus. They are surrounded by an extracellular matrix and directly contact the glomerular basement membrane in vivo. Because these interactions are critical for renal development and function, we have studied human mesangial cell interactions with laminin, a major adhesive component of basement membranes present in the extracellular matrix of the mesangium. Human fetal and adult mesangial cell attachment was stimulated by both laminin and the laminin-derived synthetic peptides YIGSR-NH2, CQAGTFALRGDNPQG-NH2, and CIKVAVS-NH2. Furthermore, mesangial cells spread on laminin as well as on both the RGD-containing and CIKVAVS peptides. When added in solution, all three peptides inhibited mesangial cell attachment to laminin, and the latter two peptides inhibited mesangial cell spreading on laminin. Laminin affinity column chromatography demonstrated several low-molecular-mass laminin-binding proteins ranging from between 35 and 42 kDa, which predominated in fetal mesangial cells, whereas a higher molecular mass laminin-binding protein of 65 kDa was predominant in adult mesangial cells. Western blot analysis with an anti-32-kDa laminin-binding protein antibody showed increased expression of both 31- and 42-kDa proteins in fetal mesangial cells when compared with the adult. The antisera to the 32-kDa laminin-binding protein also inhibited fetal mesangial spreading on the CIKVAVS peptide. Western blot analysis with an anti-67-kDa laminin-binding protein antibody revealed a 110-kDa protein in adult mesangial cells that was not present in fetal mesangial cells. These data demonstrate that multiple sites on laminin are involved in mesangial cell-laminin interactions and that the expression and type of laminin-binding proteins differ in adult and fetal mesangial cells. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NR 37 TC 17 Z9 17 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 OCT PY 1991 VL 261 IS 4 BP F688 EP F695 PN 2 PG 8 WC Physiology SC Physiology GA GK869 UT WOS:A1991GK86900108 PM 1928380 ER PT J AU CASTILLO, CE LILLIOJA, S AF CASTILLO, CE LILLIOJA, S TI PERIPHERAL LYMPHATIC CANNULATION FOR PHYSIOLOGICAL ANALYSIS OF INTERSTITIAL FLUID COMPARTMENT IN HUMANS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE TISSUE HORMONES; TISSUE SUBSTRATES; DIRECT CONTINUOUS LYMPH SAMPLING; CAPILLARY MEMBRANE TRANSFER ID PROTEIN CONCENTRATION; INSULIN ACTION; FLOW; MICRODIALYSIS; PRESSURE AB Analysis of peripheral interstitial concentrations of hormones or substrates in humans has undoubtedly been hampered by the difficulty in performing retrograde peripheral lymphatic cannulation and obtaining adequate flow rates of lymph. We now describe a technique for direct continuous sampling of peripheral lymph. A lymphatic vessel was cannulated in the lower legs of 14 males, and lymph was collected for 24-48 h. Adequate quantities of lymph were obtained basally and during physiological manipulations to make collections at 15-min intervals. Flow rates averaged 1.84 ml/h and ranged from 0.34 to 4.96 ml/h. We conclude that peripheral lymphatic vessels can be cannulated and flow rates are sufficient to measure interstitial concentration of hormones or substrates both at steady state and dynamically in adult humans. C1 NIDDKD,CLIN DIABET & NUTR SECT,4212 N 16TH ST,RM 541,PHOENIX,AZ 85016. RI Lillioja, Stephen/A-8185-2012 NR 28 TC 9 Z9 9 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD OCT PY 1991 VL 261 IS 4 BP H1324 EP H1328 PN 2 PG 5 WC Physiology SC Physiology GA GK869 UT WOS:A1991GK86900046 ER PT J AU MIYATA, H SILVERMAN, HS SOLLOTT, SJ LAKATTA, EG STERN, MD HANSFORD, RG AF MIYATA, H SILVERMAN, HS SOLLOTT, SJ LAKATTA, EG STERN, MD HANSFORD, RG TI MEASUREMENT OF MITOCHONDRIAL FREE CA2+ CONCENTRATION IN LIVING SINGLE-RAT CARDIAC MYOCYTES SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE CYTOSOLIC CALCIUM CONCENTRATION; MANGANESE; INDO-1 ID FREE CA-2+ CONCENTRATION; PYRUVATE-DEHYDROGENASE INTERCONVERSION; FLUORESCENT CALCIUM INDICATORS; MATRIX FREE CA-2+; HEART-MITOCHONDRIA; SARCOPLASMIC-RETICULUM; INTRAMITOCHONDRIAL METABOLISM; INOTROPIC AGENTS; FREE MAGNESIUM; RUTHENIUM RED AB A technique that allows the continuous measurement of mitochondrial free Ca2+ ([Ca2+]m) in a single living cardiac myocyte is described. It involves the introduction of the fluorescent chelating agent indo-1 into the cell by exposure to the acetoxymethyl ester, followed by selective quenching of the fluorescence of indo-1 in the cytosol by Mn2+. The identity of the remaining fluorescence due to intramitochondrial indo-1 is established by its resistance to treatment of the cell with digitonin at concentrations that release cytosolic but not mitochondrial enzymes and by the finding that ruthenium red and carbonyl cyanide p-trifluoromethoxyphenylhydrazone prevent its response to elevated cytosolic free Ca2+ ([Ca2+]c). [Ca2+]m is found to be low (< 100 nM) in unstimulated cells and to rise in procedures that chronically elevate [Ca2+]c, such as Na+ replacement. The gradient [Ca2+]m/[Ca2+]c is less than unity at values of [Ca2+]c of < 500 nM but rapidly increases at higher values of [Ca2+]c. Although there is no detectable increase in [Ca2+]m during a single electrical stimulation, [Ca2+]m increases up to 600 nM as the pacing frequency is raised to 4 Hz in the presence of norepinephrine; this increase occurs over the course of many contractions. It is concluded that these findings are consistent with an increase in [Ca2+]m acting as a signal to increase dehydrogenase activity, and hence flux through oxidative phosphorylation, in response to increased work loads. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. JOHNS HOPKINS MED INST,DEPT MED,DIV CARDIOL,BALTIMORE,MD 21205. NR 60 TC 337 Z9 342 U1 1 U2 4 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 OCT PY 1991 VL 261 IS 4 BP H1123 EP H1134 PN 2 PG 12 WC Physiology SC Physiology GA GK869 UT WOS:A1991GK86900022 PM 1928394 ER PT J AU BARANIUK, JN KALINER, M AF BARANIUK, JN KALINER, M TI NEUROPEPTIDES AND NASAL SECRETION SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Review DE SUBSTANCE-P; NEUROKININ-A; TACHYKININS; CALCITONIN GENE-RELATED PEPTIDE; VASOACTIVE INTESTINAL PEPTIDE; NEUROPEPTIDE-Y; MUCUS SECRETION; VASCULAR PERMEABILITY ID GENE-RELATED PEPTIDE; GASTRIN-RELEASING PEPTIDE; VASOACTIVE-INTESTINAL-PEPTIDE; BRADYKININ-INDUCED BRONCHOCONSTRICTION; AIRWAY NEUTRAL ENDOPEPTIDASE; CANINE TRACHEAL EPITHELIUM; GOBLET CELL SECRETION; GUINEA-PIG TRACHEA; SUBSTANCE-P; SENSORY NEURONS AB The nasal mucosa is innervated by the sensory, parasympathetic, and sympathetic nervous systems. Nociceptive sensory nerves are stimulated by mucosal injury, inhalation of irritants, or mast cell degranulation and release of the calcitonin gene-related peptide, the tachykinins substance P and neurokinin A, and other peptides by the axon response mechanism. Sensory nerve stimulation initiates systemic reflexes, such as the sneeze, and central parasympathetic reflexes which release acetylcholine, vasoactive intestinal peptide, and other peptides and lead to glandular secretion. In concert, these proinflammatory neural responses lead to vasodilation, vascular permeability, and glandular secretion. Sympathetic nerves release neuropeptide Y and norepinephrine, potent vasoconstrictors which act to decompress the nasal mucosa and produce nasal patency. The balance between the effects of parasympathetic and sympathetic neurotransmitters may regulate nasal homoeostasis, whereas the nociceptive sensory system may be held in reserve as a defense mechanism. Dysfunction of these systems may lead to pathological nasal syndromes. In the future, specific neuropeptide agonists and antagonists may be useful for the treatment of human rhinitic diseases. C1 NIAID, CLIN INVEST LAB, ALLERG DIS SECT, BETHESDA, MD 20892 USA. NATL HEART & LUNG INST, DEPT THORAC MED, LONDON SW3 6LY, ENGLAND. NR 151 TC 53 Z9 53 U1 0 U2 1 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 OCT PY 1991 VL 261 IS 4 BP L223 EP L235 PN 1 PG 13 WC Physiology SC Physiology GA GK867 UT WOS:A1991GK86700059 PM 1928355 ER PT J AU CORYELL, W ENDICOTT, J KELLER, MB AF CORYELL, W ENDICOTT, J KELLER, MB TI PREDICTORS OF RELAPSE INTO MAJOR DEPRESSIVE DISORDER IN A NONCLINICAL POPULATION SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID FOLLOW-UP AB Objective: This study sought to describe the natural history of major depressive disorder in a large group of nonclinical subjects. In particular, the analysis determined demographic and clinical risk factors for the recurrence of major depressive disorder. Method: Relatives, comparison subjects (matched to relatives for age and sex), and spouses of affectively ill probands underwent structured clinical assessments before and after a 6-year interval. Results: Of 396 individuals who had had only major depressive disorder that ended before the initial evaluation, 33.8% (N = 134) developed a new episode during the 6-year follow-up period. Youth, but not sex, was an important demographic risk factor. The presence of minor depression at the time of initial evaluation and the number of symptoms recalled from the worst previous episode were additional clinical risk factors. At the initial evaluation, 200 other subjects had described a previous history of both major depressive disorder and a nonaffective mental disorder. When compared to the subjects who recalled only a history of major depressive disorder, these subjects were more likely to have been in an episode of chronic intermittent depression at the initial evaluation and to recall a greater number of episodes as well as a greater number of symptoms in the worst episode. A history of a nonaffective mental disorder significantly increased the risk of relapse into major depressive disorder. Conclusions: These findings agree well with a recent review of clinically based follow-up studies. Thus, youth and a history of nonaffective illness are important risk factors for the recurrence of major affective disorder in a broad variety of settings. C1 NIMH,COLLABORAT PROGRAM PSYCHOBIOL DEPRESS CLIN STUDIES,BETHESDA,MD 20892. FU NIMH NIH HHS [R01 MH025478] NR 12 TC 84 Z9 84 U1 1 U2 2 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 OCT PY 1991 VL 148 IS 10 BP 1353 EP 1358 PG 6 WC Psychiatry SC Psychiatry GA GH487 UT WOS:A1991GH48700011 PM 1897616 ER PT J AU BECKER, RL VENZON, D LACK, EE MIKEL, UV WEISS, SW OLEARY, TJ AF BECKER, RL VENZON, D LACK, EE MIKEL, UV WEISS, SW OLEARY, TJ TI CYTOMETRY AND MORPHOMETRY OF MALIGNANT FIBROUS HISTIOCYTOMA OF THE EXTREMITIES - PREDICTION OF METASTASIS AND MORTALITY SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE MALIGNANT FIBROUS HISTIOCYTOMA; COMPUTER-ASSISTED IMAGE PROCESSING; FLOW CYTOMETRY ID SOFT-TISSUE SARCOMAS; MULTIVARIATE-ANALYSIS; PROGNOSTIC FACTORS; IMAGE-ANALYSIS; DNA; TUMORS; CYTOPHOTOMETRY; SURVIVAL; NECROSIS AB Flow cytometry and nuclear morphometry were compared with traditional pathologic grading techniques for predicting the course of malignant fibrous histiocytoma of the extremities. Clinical, pathologic, and flow/morphometric variables from 53 cases were tested by Cox regression for prediction of distant recurrence and mortality. Tumor grading based on extent of tumor necrosis was a significant predictor for both disease-free survival (p = .014) and overall survival (p = .003). The fraction of nuclei in the S + G2M segment of DNA histograms was significant for disease-free survival (p = .007), and remained significant (p = .033) in a joint Cox model with necrosis-based grade (p = .004 for the bivariate model). Relative risk for recurrence varied nearly 10x between the 10th and 90th percentiles of grade and (S + G2M)1/2. Overall survival was predicted by a nuclear shape feature termed "R" (p = .000008), the casewise difference (residual) between expected and observed nuclear perimeter as a function of average Feret diameter. In a bivariate Cox model, relative risk of mortality varied 35x between the 10th and 90th percentiles of grade and R. Cytometric and morphometric data contain information about recurrence-free and overall survival beyond that available from more usual clinical and pathologic features. It seems likely that nuclear morphometry, in particular, will prove to be a useful aid for estimating the prognosis of patients with malignant fibrous histiocytoma of the extremities. C1 NCI,DCT,COP,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. GEORGETOWN UNIV,SCH MED,DEPT PATHOL,WASHINGTON,DC 20057. UNIV MICHIGAN,DEPT PATHOL,ANN ARBOR,MI 48109. RP BECKER, RL (reprint author), ARMED FORCES INST PATHOL,DEPT CELLULAR PATHOL,RM 1021,BLDG 54,WASHINGTON,DC 20306, USA. RI Venzon, David/B-3078-2008 NR 24 TC 29 Z9 29 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 1991 VL 15 IS 10 BP 957 EP 964 DI 10.1097/00000478-199110000-00006 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA GG486 UT WOS:A1991GG48600006 PM 1656800 ER PT J AU PHELPS, KR GINSBERG, SS CUNNINGHAM, AW TSCHACHLER, E DOSIK, H AF PHELPS, KR GINSBERG, SS CUNNINGHAM, AW TSCHACHLER, E DOSIK, H TI CASE-REPORT - ADULT T-CELL LEUKEMIA LYMPHOMA ASSOCIATED WITH RECURRENT STRONGYLOIDES HYPERINFECTION SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I (HTLV-1); ADULT T-CELL LEUKEMIA LYMPHOMA (ATLL); STRONGYLOIDIASIS ID ACQUIRED IMMUNE-DEFICIENCY; HTLV-I; STERCORALIS INFECTION; UNITED-STATES; PROVIRAL DNA; VIRUS; PATIENT; DIFFERENTIATION; IMMUNOLOGY; FEATURES AB Adult T-cell leukemia/lymphoma (ATLL) was demonstrated postmortem in a 47-year-old woman initially manifesting severe hypercalcemia and a vertebral compression fracture. Hyperinfection with Strongyloides stercoralis preceded the appearance of ATLL by several months and ultimately dominated the terminal course. Although HTLV-I and S. stercoralis commonly infect the same host, only three other cases of concomitant ATLL and hyperinfection have been reported in English. The apparent rarity of this association suggests that immunologic sequelae of ATLL do not predispose to dissemination and multiplication of Strongyloides. Observations pertinent to this conclusion are reviewed. C1 INTERFAITH MED CTR,DEPT MED,BROOKLYN,NY. SUNY HLTH SCI CTR,DEPT MED,BROOKLYN,NY. SUNY HLTH SCI CTR,DEPT PATHOL,BROOKLYN,NY. NCI,BETHESDA,MD 20892. NR 35 TC 21 Z9 23 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD OCT PY 1991 VL 302 IS 4 BP 224 EP 228 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA GJ516 UT WOS:A1991GJ51600006 PM 1928233 ER PT J AU PETERSON, DS DISANTI, SM POVOA, M CALVOSA, VS DOROSARIO, VE WELLEMS, TE AF PETERSON, DS DISANTI, SM POVOA, M CALVOSA, VS DOROSARIO, VE WELLEMS, TE TI PREVALENCE OF THE DIHYDROFOLATE-REDUCTASE ASN-108 MUTATION AS THE BASIS FOR PYRIMETHAMINE-RESISTANT FALCIPARUM-MALARIA IN THE BRAZILIAN AMAZON SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID THYMIDYLATE SYNTHASE GENE; POLYMERASE CHAIN-REACTION; PARASITE PLASMODIUM-FALCIPARUM; ANTIMALARIAL-DRUGS; POINT MUTATIONS; MOLECULAR-BASIS; SUSCEPTIBILITY; AMPLIFICATION; CYCLOGUANIL; SENSITIVITY AB Pyrimethamine resistance in cultivated laboratory isolates of Plasmodium falciparum is linked to the dihydrofolate reductase mutation Asn-108, a mutation that acts by interrupting drug binding within the active site of the enzyme. To determine the prevalence of this mutation in endemic regions harboring pyrimethamine-resistant malaria, we used a mutation-specific polymerase chain reaction assay to survey P. falciparum strains from a wide section of the Brazilian Amazon. Mutations were identified directly from blood samples without intervening steps of in vitro cultivation. Of 42 samples collected from four states in Brazil, 38 (90%) contained the Asn-108 codon AAC that confers pyrimethamine resistance, four samples contained only the wild-type Ser-108 codon AGC, and none contained the Thr-108 codon ACC found in cycloguanil-resistant pyrimethamine-sensitive strains. These findings indicate that a very high incidence of the Asn-108 DHFR mutation is responsible for pyrimethamine resistance in the Amazon, and they are consistent with recent failure rates reported for Fansidar (pyrimethamine-sulfadoxine). We suggest that limited use of proguanil be evaluated as an alternative to pyrimethamine. C1 NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892. SUPERINTENDENCIA CONTROL ENDEMIAS,SAO PAULO,BRAZIL. INST EVANDRO CHAGAS FUNDACAO SESP,BELEM,BRAZIL. INST HIGIENE & MED TROP,LISBON,PORTUGAL. RI Di Santi, Silvia/D-8973-2012 NR 28 TC 78 Z9 79 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD OCT PY 1991 VL 45 IS 4 BP 492 EP 497 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA GN354 UT WOS:A1991GN35400012 PM 1951858 ER PT J AU BARTKO, JJ AF BARTKO, JJ TI PROVING THE NULL HYPOTHESIS SO AMERICAN PSYCHOLOGIST LA English DT Letter RP BARTKO, JJ (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 6 TC 7 Z9 7 U1 0 U2 2 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 OCT PY 1991 VL 46 IS 10 BP 1089 EP 1089 PG 1 WC Psychology, Multidisciplinary SC Psychology GA GH652 UT WOS:A1991GH65200018 ER PT J AU HOOVER, DR GRAHAM, NMH BACELLAR, H SCHRAGER, LK KASLOW, R VISSCHER, B MURPHY, R ANDERSON, R SAAH, A AF HOOVER, DR GRAHAM, NMH BACELLAR, H SCHRAGER, LK KASLOW, R VISSCHER, B MURPHY, R ANDERSON, R SAAH, A TI EPIDEMIOLOGIC PATTERNS OF UPPER RESPIRATORY ILLNESS AND PNEUMOCYSTIS-CARINII PNEUMONIA IN HOMOSEXUAL MEN SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PULMONARY INFECTIOUS COMPLICATIONS; SEQUENCE; CHILDREN; OUTBREAK; COHORT; FUNGI; AIDS AB The relationship between self-reported upper respiratory illness symptoms (URI) and human immunodeficiency virus Type 1 (HIV-1) was examined in homosexual men using semiannual visits from 1984 to 1988. Temporal and geographic patterns of Pneumocystis carinii pneumonia (PCP) diagnosis in these men during the same time period are also described. URI, including acute sinusitis, was reported more often by 916 HIV-1-seropositive participants than by 2,161 seronegative participants (32.21 versus 28.86% p < 0.001). For 387 seropositive subjects who progressed to acquired immunodeficiency syndrome (AIDS), the proportion reporting URI peaked one visit pre-AIDS at a level significantly higher than matched control subjects (0.45 versus 0.28, p less-than-or-equal-to 0.001). The peak was higher for those with PCP as an initial diagnosis. Reported URI peaked in winter and troughed in summer, and PCP diagnosis rates peaked and troughed 4 months later, respectively. Cities with the highest reported rates of URI also had the highest proportions of AIDS cases with PCP as an initial diagnosis. No temporal or geographic patterns were observed for other HIV-1-related symptoms or non-PCP AIDS diagnoses. These patterns suggest the possibility of a person-to-person transmission of P. carinii similar to that of other respiratory pathogens, which would imply a need to consider stricter methods to prevent nosocomial transmission of this pathogen in inpatient and outpatient settings. Further investigation of these issues is needed. C1 NIAID,EPIDEMIOL BRANCH,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,LOS ANGELES SCH PUBL HLTH,DEPT BIOSTAT,LOS ANGELES,CA 90024. JOHNSON COMPREHENS CANC CTR,CANC CTR BIOMETRY SECT,LOS ANGELES,CA. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL 60611. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT INFECT DIS & IMMUNOL,PITTSBURGH,PA 15260. RP HOOVER, DR (reprint author), JOHNS HOPKINS UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,624 N BROADWAY,BALTIMORE,MD 21205, USA. OI Murphy, Robert/0000-0003-3936-2052 FU NIAID NIH HHS [AI-72634, AI-72632, AI-72631] NR 23 TC 34 Z9 34 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD OCT PY 1991 VL 144 IS 4 BP 756 EP 759 PG 4 WC Respiratory System SC Respiratory System GA GJ505 UT WOS:A1991GJ50500005 PM 1928944 ER PT J AU LEVINE, SJ MASUR, H GILL, VJ FEUERSTEIN, I SUFFREDINI, AF BROWN, D LANE, HC YARCHOAN, R SHELHAMER, JH OGNIBENE, FP AF LEVINE, SJ MASUR, H GILL, VJ FEUERSTEIN, I SUFFREDINI, AF BROWN, D LANE, HC YARCHOAN, R SHELHAMER, JH OGNIBENE, FP TI EFFECT OF AEROSOLIZED PENTAMIDINE PROPHYLAXIS ON THE DIAGNOSIS OF PNEUMOCYSTIS-CARINII PNEUMONIA BY INDUCED SPUTUM EXAMINATION IN PATIENTS INFECTED WITH THE HUMAN-IMMUNODEFICIENCY-VIRUS SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Article ID AIDS PATIENTS; ANTIBODY AB This study assessed the effect of aerosolized pentamidine prophylaxis on the clinical presentation and diagnostic sensitivity of induced sputum examination for Pneumocystis carinii pneumonia. Between January 1, 1988 and October 27, 1990, 348 induced sputum examinations were performed as the initial diagnostic procedure for P. carinii pneumonia in patients infected with the human immunodeficiency virus (HIV). Medical records were reviewed for all induced sputum examinations, and the study group consisted of patients who either had not received prophylactic therapy (n = 193) or had received aerosolized pentamidine prophylaxis (n = 126). A total of 29 induced sputum examinations in patients receiving either other prophylactic regimens or ongoing therapy for previously documented P. carinii pneumonia were excluded from the study group. A total of 72 consecutive episodes of P. carinii pneumonia were subsequently documented by induced sputum examination (n = 54), bronchoalveolar lavage (n = 16), thoracocentesis (n = 1), or autopsy (n = 1). A total of 44 episodes occurred in patients who had not received antipneumocystis prophylaxis, and 28 episodes occurred in patients who had received aerosolized pentamidine. Of patients capable of producing a sputum specimen for analysis, induced sputum examination had a significantly lower diagnostic yield of 64.3% in patients who had received aerosolized pentamidine prophylaxis compared with 92.3% in patients who did not receive prophylaxis (p < 0.02, Fisher's exact test). When the data were analyzed on an intention to treat basis, although there was a trend suggesting a lower overall yield in the aerosolized pentamidine patients, the difference was not statistically significant (64.3 versus 81.8%, p = 0.17, Fisher's exact test). There was no significant difference in duration of symptoms, alveolar-arterial oxygen gradient, presenting radiographic manifestations, or burden of organisms (in patients with positive induced sputum examinations) between the two groups. However, there was a trend toward an increased incidence of focal upper lobe infiltrates in the aerosolized pentamidine group (p = 0.054, Fisher's exact test). We conclude that aerosolized pentamidine prophylaxis is associated with a significantly lower diagnostic yield (64.3%) of induced sputum examination for P. carinii pneumonia in HIV-infected patients if a specimen is obtained for analysis. Nevertheless, its yield is high enough such that an induced sputum examination should still be considered the initial diagnostic procedure for suspected P. carinii pneumonia in these patients. C1 NIAID,WARREN G MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BLDG 10,ROOM 7-D43,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. NIAID,WARREN G MAGNUSON CLIN CTR,DEPT RADIOL,BETHESDA,MD 20892. NIAID,WARREN G MAGNUSON CLIN CTR,DEPT MICROBIOL,BETHESDA,MD 20892. NR 24 TC 67 Z9 67 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD OCT PY 1991 VL 144 IS 4 BP 760 EP 764 PG 5 WC Respiratory System SC Respiratory System GA GJ505 UT WOS:A1991GJ50500006 PM 1928945 ER PT J AU STEINBERG, AD GOURLEY, MF KLINMAN, DM TSOKOS, GC SCOTT, DE KRIEG, AM AF STEINBERG, AD GOURLEY, MF KLINMAN, DM TSOKOS, GC SCOTT, DE KRIEG, AM TI SYSTEMIC LUPUS-ERYTHEMATOSUS SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE LUPUS ERYTHEMATOSUS, SYSTEMIC; AUTOANTIBODIES; LYMPHOCYTES-T; BETA-LYMPHOCYTES; HEMATOPOIETIC STEM CELLS ID T-CELL SUBSETS; HISTOCOMPATIBILITY COMPLEX GENES; FRAGMENT-LENGTH-POLYMORPHISM; RECOMBINANT INBRED LINES; HEAT-SHOCK PROTEINS; B-CELLS; AUTOIMMUNE-DISEASE; GROWTH-FACTOR; PERIPHERAL-BLOOD; MURINE LUPUS AB Although the cause of systemic lupus erythematosus remains unknown, pathogenic mechanisms are becoming clearer. Both genetic and environmental factors have been implicated in the induction and in the perpetuation of lupus. Implicated environmental triggers include ultraviolet light, chemicals (hydrazines, hair dyes, drugs), some foods, and possibly infectious agents. Lupus is mediated by the immune system. Patients have excess numbers of antibody-forming cells, including those that produce antibodies reactive with self-antigens. Patients also have an increased number of activated T cells, some of which help B cells to produce autoantibodies. A loss of tolerance is a critical immune abnormality in lupus; many of the activated helper T cells may result from a failure in normal tolerance mechanisms. A hematopoietic stem-cell defect could give rise to both B- and T-cell abnormalities. Such a stem-cell abnormality might lead to both a loss of self-tolerance and polyclonal B-cell activation. Antigen-driven, T-cell-dependent expansion of B-cell clones would then give rise to pathogenic autoantibodies, including anti-DNA. We believe that lupus is a syndrome: Patients differ regarding specific inciting factors and immune defects. Some patients have genetically conditioned abnormalities, similar to those found in mice with lupus; others have a combination of genetic and acquired defects. We hope that insights into pathogenesis lead to improved and more individualized therapy. RP STEINBERG, AD (reprint author), NIH,BLDG 10,ROOM 9N218,BETHESDA,MD 20892, USA. NR 120 TC 97 Z9 97 U1 1 U2 5 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 1 PY 1991 VL 115 IS 7 BP 548 EP 559 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA GG283 UT WOS:A1991GG28300008 PM 1883125 ER PT J AU SCHWAN, TG SIMPSON, WJ AF SCHWAN, TG SIMPSON, WJ TI DIAGNOSING LYME-DISEASE SO ANNALS OF INTERNAL MEDICINE LA English DT Letter ID ARTHRITIS; TICKS RP SCHWAN, TG (reprint author), NIAID,ROCKY MT LABS,HAMILTON,MT 59840, USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 1 PY 1991 VL 115 IS 7 BP 577 EP 578 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA GG283 UT WOS:A1991GG28300018 PM 1883132 ER PT J AU HAMILTON, JM AF HAMILTON, JM TI MULTIPLE CONFIRMATORY TRIALS - HOW CAN ADDITIONAL STUDIES BE OF VALUE SO ANNALS OF ONCOLOGY LA English DT Editorial Material ID METASTATIC COLORECTAL-CARCINOMA; CLINICAL-TRIALS; FOLINIC ACID; FLUOROURACIL; 5-FLUOROURACIL; CANCER RP HAMILTON, JM (reprint author), NCI,BETHESDA,MD 20892, USA. NR 17 TC 4 Z9 4 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 1991 VL 2 IS 9 BP 625 EP 627 PG 3 WC Oncology SC Oncology GA GM214 UT WOS:A1991GM21400005 PM 1742218 ER PT J AU PARENTEAU, GL CLARK, RE AF PARENTEAU, GL CLARK, RE TI PREVENTION OF ISCHEMIA-REPERFUSION INJURY BY THE ALLERGY DRUG LODOXAMIDE TROMETHAMINE SO ANNALS OF THORACIC SURGERY LA English DT Article ID SUPEROXIDE-DISMUTASE; XANTHINE-OXIDASE; FREE-RADICALS; INFARCT SIZE; REDUCTION; ALLOPURINOL; CATALASE; TISSUE; HEART AB Lodoxamide tromethamine, an orphan antiallergy drug, inhibits degranulation of mast cells that reside in the myocardium and inhibits xanthine oxidase located in myocytes and predominately in the vascular endothelium. The hypothesis evaluated was that lodoxamide tromethamine would attenuate oxygen free radical damage. Isolated working rat hearts were perfused with Krebs-Henseleit buffer containing 0, 1, 10, 100, or 1,000-mu-mol/L lodoxamide tromethamine at 37-degrees and 24-degrees-C with ischemic times of 22 and 93 minutes, respectively. These ischemic intervals yielded 50% survival and 50% return of function in untreated hearts. Lodoxamide treatment alone at the onset of reperfusion was also studied. Performance end points were aortic flow, pressure, and coronary flow. Biochemical analyses included serotonin collected from coronary effluent as a marker of mast cell degranulation, uric acid for xanthine oxidase inhibition, myocardial adenosine triphosphate, and carbonyl group concentrations. Performance data demonstrated that lodoxamide was beneficial in a log-linear dose response when given continuously at both temperatures. Percent of preischemic values for untreated and maximal responses at 1,000-mu-mol/L of lodoxamide were as follows: a mortality of 50% in nontreated hearts versus 0%; aortic flow, 47% to 94% (37-degrees-C), 46% to 86% (24-degrees-C); cardiac output, 60% to 98% (37-degrees-C), 58% to 97% (24-degrees-C); adenosine triphosphate, 59% to 90% (37-degrees-C), 48% to 65% (24-degrees-C). Serotonin was undetectable from any hearts. Uric acid concentrations and carbonyl group content did not change with increasing dose. Lodoxamide demonstrated no benefit when given only during reperfusion, suggesting injury occurred at times other than reperfusion. RP PARENTEAU, GL (reprint author), NHLBI,DIV INTRAMURAL RES,BLDG 10,RM 7N218,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 21 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD OCT PY 1991 VL 52 IS 4 BP 832 EP 838 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA GM201 UT WOS:A1991GM20100019 PM 1929638 ER PT J AU FASS, R VANDEWALLE, M SHILOACH, A JOSLYN, A KAUFMAN, J SHILOACH, J AF FASS, R VANDEWALLE, M SHILOACH, A JOSLYN, A KAUFMAN, J SHILOACH, J TI USE OF HIGH-DENSITY CULTURES OF ESCHERICHIA-COLI FOR HIGH-LEVEL PRODUCTION OF RECOMBINANT PSEUDOMONAS-AERUGINOSA EXOTOXIN-A SO APPLIED MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article ID PROTEINS; EXPRESSION; FERMENTER; DELETION AB An efficient fermentation method for the production of two modified recombinant Pseudomonas aeruginosa exotoxin As cloned in Escherichia coli BL21(lambda-DE3) was developed. Cell densities of 16-30 g dry weight/1 were found to be most suitable for the induction of protein synthesis, which was under the isopropyl beta-D-thiogalactopyranoside (IPTG)-inducible T7 expression system. A concentration of 0.6 mM IPTG and induction time of 90 min were found to give the best results for production of the modified toxins. Using this procedure, gram amounts of the proteins were obtained in a 3-1 bench-top fermentor. The high density growth of the bacteria did not impair the integrity of the proteins and did not interfere with the purification procedure. C1 NIDDK,LCDB,BIOTECHNOL UNIT,BLDG 6,ROOM B1-33,BETHESDA,MD 20892. ISRAEL INST BIOL RES,IL-70450 NESS ZIONA,ISRAEL. NR 19 TC 29 Z9 32 U1 3 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0175-7598 J9 APPL MICROBIOL BIOT JI Appl. Microbiol. Biotechnol. PD OCT PY 1991 VL 36 IS 1 BP 65 EP 69 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA GM449 UT WOS:A1991GM44900012 PM 1367778 ER PT J AU CHAMULITRAT, W HUGHES, MF ELING, TE MASON, RP AF CHAMULITRAT, W HUGHES, MF ELING, TE MASON, RP TI SUPEROXIDE AND PEROXYL RADICAL GENERATION FROM THE REDUCTION OF POLYUNSATURATED FATTY-ACID HYDROPEROXIDES BY SOYBEAN LIPOXYGENASE SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID ELECTRON-SPIN-RESONANCE; PURE RETICULOCYTE LIPOXYGENASE; AQUEOUS-SOLUTION; LINOLEIC-ACID; ALKOXYL RADICALS; HEMATIN; SPECTROSCOPY; CONVERSION; 7,8-DIHYDROXY-7,8-DIHYDROBENZOPYRENE; DECOMPOSITION RP CHAMULITRAT, W (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 46 TC 69 Z9 69 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD OCT PY 1991 VL 290 IS 1 BP 153 EP 159 DI 10.1016/0003-9861(91)90601-E PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GE531 UT WOS:A1991GE53100019 PM 1654862 ER PT J AU WAXMAN, DJ LAPENSON, DP AOYAMA, T GELBOIN, HV GONZALEZ, FJ KORZEKWA, K AF WAXMAN, DJ LAPENSON, DP AOYAMA, T GELBOIN, HV GONZALEZ, FJ KORZEKWA, K TI STEROID-HORMONE HYDROXYLASE SPECIFICITIES OF 11 CDNA-EXPRESSED HUMAN CYTOCHROME-P450S SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID RAT HEPATIC CYTOCHROME-P-450; HUMAN-LIVER; DIRECTED EXPRESSION; TESTOSTERONE OXIDATION; DEPENDENT EXPRESSION; IDENTIFICATION; METABOLISM; ISOZYMES; SEQUENCE; 16-ALPHA-HYDROXYLASE C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RP WAXMAN, DJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,JF-525,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIDDK NIH HHS [DK33765, R01 DK033765] NR 38 TC 280 Z9 284 U1 2 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD OCT PY 1991 VL 290 IS 1 BP 160 EP 166 DI 10.1016/0003-9861(91)90602-F PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GE531 UT WOS:A1991GE53100020 PM 1898086 ER PT J AU LEONARD, HL SWEDO, SE LENANE, MC RETTEW, DC CHESLOW, DL HAMBURGER, SD RAPOPORT, JL AF LEONARD, HL SWEDO, SE LENANE, MC RETTEW, DC CHESLOW, DL HAMBURGER, SD RAPOPORT, JL TI A DOUBLE-BLIND DESIPRAMINE SUBSTITUTION DURING LONG-TERM CLOMIPRAMINE TREATMENT IN CHILDREN AND ADOLESCENTS WITH OBSESSIVE-COMPULSIVE DISORDER SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID CONTINUATION THERAPY; TRIAL; DEPRESSION; AMITRIPTYLINE; RELIABILITY; FLUOXETINE; IMIPRAMINE; SEROTONIN; INTERVIEW; EPISODES AB Twenty-six children and adolescents with severe primary obsessive-compulsive disorder receiving long-term clomipramine hydrochloride maintenance treatment (mean +/- SD, 17.1 +/- 8.3 months; range, 4 to 32 months) entered an 8-month double-blind desipramine hydrochloride substitution study to assess the necessity of continued drug treatment. All patients received clomipramine for the first 3 months, then half continued with clomipramine therapy (nonsubstituted group) and half had desipramine blindly substituted for the next 2 months; all subjects again received clomipramine for the last 3 study months. Eight (89%) of nine of the substituted and only two (18%) of 11 of the nonsubstituted group subjects relapsed during the 2-month comparison period. Long-term clomipramine treatment seems necessary for this population of children and adolescents with obsessive-compulsive disorder. However, even patients receiving maintenance clomipramine treatment throughout the entire study had continued obsessive-compulsive symptoms, which varied in severity over time. RP LEONARD, HL (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 39 TC 153 Z9 153 U1 2 U2 4 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 OCT PY 1991 VL 48 IS 10 BP 922 EP 927 PG 6 WC Psychiatry SC Psychiatry GA GJ812 UT WOS:A1991GJ81200006 PM 1929762 ER PT J AU GELERNTER, CS UHDE, TW CIMBOLIC, P ARNKOFF, DB VITTONE, BJ TANCER, ME BARTKO, JJ AF GELERNTER, CS UHDE, TW CIMBOLIC, P ARNKOFF, DB VITTONE, BJ TANCER, ME BARTKO, JJ TI COGNITIVE-BEHAVIORAL AND PHARMACOLOGICAL TREATMENTS OF SOCIAL PHOBIA - A CONTROLLED-STUDY SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID ANXIETY DISORDER; ALPRAZOLAM; EXPOSURE; QUESTIONNAIRE; PHENELZINE; INTERVIEW AB Sixty-five patients with social phobia were treated in a study that compared a cognitive-behavioral group treatment program with pharmacotherapy with alprazolam, phenelzine sulfate, or pill-placebo plus instructions for self-directed exposure to phobic stimuli. Statistically significant repeated-measures effects were shown on all measures, indicating that the treatments studied were associated with substantial improvements in patients with severe and chronic social phobia. Patients who were treated with phenelzine were rated by clinicans as more improved on a measure of work and social disability than patients who were treated with alprazolam or placebo (patients in the cognitive-behavior therapy group were not rated on this measure). Subjects showed positive cognitive changes from before to after treatment, and there were no differences between treatment groups on the cognitive measure. We discuss the implications of these findings within the context of demographic and clinical predictors of response. C1 NIMH,BIOL PSYCHIAT BRANCH,ANXIETY & AFFECT DISORDERS SECT,BETHESDA,MD 20892. NIMH,DIV BIOMETRY & APPL SCI,BETHESDA,MD 20892. CATHOLIC UNIV AMER,CTR COUNSELING,WASHINGTON,DC 20064. CATHOLIC UNIV AMER,DEPT PSYCHOL,WASHINGTON,DC 20064. FU NIMH NIH HHS [T32MH14235] NR 37 TC 302 Z9 306 U1 5 U2 19 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 OCT PY 1991 VL 48 IS 10 BP 938 EP 945 PG 8 WC Psychiatry SC Psychiatry GA GJ812 UT WOS:A1991GJ81200008 PM 1929764 ER PT J AU CAPORASO, NE SHAW, GL AF CAPORASO, NE SHAW, GL TI CLINICAL IMPLICATIONS OF THE COMPETITIVE-INHIBITION OF THE DEBRISOQUIN-METABOLIZING ISOZYME BY QUINIDINE SO ARCHIVES OF INTERNAL MEDICINE LA English DT Review ID HUMAN-LIVER MICROSOMES; GENETIC-POLYMORPHISM; EXTENSIVE METABOLIZERS; DRUG OXIDATION; POOR METABOLIZERS; HYDROXYLATION POLYMORPHISM; DOSE QUINIDINE; PHENFORMIN 4-HYDROXYLATION; MEPHENYTOIN HYDROXYLATION; AMITRIPTYLINE METABOLISM AB Approximately 10% of western populations are genetically deficient in the enzyme that metabolizes the antihypertensive drug debrisoquin. These "poor metabolizers" process many common medications in an aberrant fashion, resulting in a variety of untoward consequences including exaggerated drug effect, subtherapeutic drug concentrations, or complex drug interactions. A variety of medications, including neuroleptics, antidepressants, beta-blockers, and certain antiarrhythmics, are subject to the influence of this metabolic polymorphism. Quinidine administration changes persons to poor metabolizers of debrisoquin for the duration of therapy. Thus, the use of quinidine with any of the other drugs metabolized by this isozyme may be expected to result in a drug interaction in which a person's response will mimic that of a poor metabolizer. Because no test is commonly available to determine directly the debrisoquin metabolic phenotype, clinicians should be alert to unusual drug reactions in patients receiving quinidine concurrently with the other medications. RP CAPORASO, NE (reprint author), NCI, ENVIRONM EPIDEMIOL BRANCH, EPN 439, 6130 EXECUT BLVD, ROCKVILLE, MD 20892 USA. NR 127 TC 25 Z9 25 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-9926 EI 1538-3679 J9 ARCH INTERN MED JI Arch. Intern. Med. PD OCT PY 1991 VL 151 IS 10 BP 1985 EP 1992 DI 10.1001/archinte.151.10.1985 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA GK641 UT WOS:A1991GK64100011 PM 1681790 ER PT J AU HUGHES, JR GUST, SW KEENAN, R FENWICK, JW SKOOG, K HIGGINS, ST AF HUGHES, JR GUST, SW KEENAN, R FENWICK, JW SKOOG, K HIGGINS, ST TI LONG-TERM USE OF NICOTINE VS PLACEBO GUM SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CHEWING-GUM; SMOKING CESSATION; CONTROLLED TRIAL; WITHDRAWAL SYMPTOMS; DOUBLE-BLIND; CHRONIC PAIN; WEIGHT-GAIN; INTERVENTION; INSTRUCTIONS; DEPENDENCE AB Medical patients (n = 315) who wished to quit smoking were randomly assigned in a double-blind manner to receive either nicotine or placebo gum. Subjects were advised to stop gum use by 4 months. Among abstinent smokers, 46% of those receiving nicotine gum and 17% of those receiving placebo gum used the gum beyond the recommended 4-month period. By 10 months after cessation 17% of quitters receiving nicotine gum and 6% receiving placebo gum were still using gum. Gradual reduction of nicotine gum did not result in withdrawal and cessation of nicotine gum did not increase the probability of relapse to smoking or weight gain. We conclude that use of nicotine gum is due, in part, to the effects of nicotine; however, long-term use is uncommon. C1 UNIV VERMONT,DEPT PSYCHOL,BURLINGTON,VT 05401. UNIV VERMONT,DEPT FAMILY PRACTICE,BURLINGTON,VT 05401. UNIV VERMONT,DEPT MED BIOSTAT,BURLINGTON,VT 05401. NIDA,ROCKVILLE,MD. UNIV MINNESOTA,DEPT PSYCHIAT,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,DEPT PSYCHOL,MINNEAPOLIS,MN 55455. RP HUGHES, JR (reprint author), UNIV VERMONT,COLL MED,DEPT PSYCHIAT,HUMAN BEHAV PHARMACOL LAB,38 FLETCHER PL,BURLINGTON,VT 05401, USA. FU NIDA NIH HHS [DA-03728, DA-04066, DA-0298] NR 51 TC 42 Z9 44 U1 0 U2 2 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 OCT PY 1991 VL 151 IS 10 BP 1993 EP 1998 DI 10.1001/archinte.151.10.1993 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA GK641 UT WOS:A1991GK64100012 PM 1929687 ER PT J AU GRAFMAN, J RAO, S BERNARDIN, L LEO, GJ AF GRAFMAN, J RAO, S BERNARDIN, L LEO, GJ TI AUTOMATIC MEMORY PROCESSES IN PATIENTS WITH MULTIPLE-SCLEROSIS SO ARCHIVES OF NEUROLOGY LA English DT Article ID FREQUENCY; DISTURBANCE; IMPAIRMENT; DEMENTIA; DISEASE AB To better understand the nature of the memory deficit in patients with multiple sclerosis, we designed a study to compare automatic vs effortful memory processes. Forty-one patients with definite multiple sclerosis and 45 demographically matched normal control subjects were administered two tasks designed to assess both automatic (monitoring frequency and modality) and effortful (free and cued-recall) processing. Results indicated that patients with multiple sclerosis, as expected, were significantly impaired on memory measures requiring effort, but performed normally on automatic measures. Performance on the memory indexes did not correlate with self-reported depression. The implications of these findings for delineating the locus of the memory impairment in multiple sclerosis is discussed. C1 MED COLL WISCONSIN,DEPT NEUROL,NEUROPSYCHOL SECT,MILWAUKEE,WI 53226. RP GRAFMAN, J (reprint author), NINCDS,MED NEUROL BRANCH,COGNIT NEUROSCI SECT,BLDG 10,ROOM 5C422,BETHESDA,MD 20892, USA. RI Rao, Stephen/A-2460-2010; OI Rao, Stephen/0000-0002-6463-7460; Grafman, Jordan H./0000-0001-8645-4457 FU NINDS NIH HHS [K04 NS 01055-05, R01 NS 22128-06] NR 34 TC 76 Z9 76 U1 2 U2 7 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 OCT PY 1991 VL 48 IS 10 BP 1072 EP 1075 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA GJ526 UT WOS:A1991GJ52600017 PM 1929900 ER PT J AU FREEDMAN, J RUBIN, B AF FREEDMAN, J RUBIN, B TI MOLTENO IMPLANTS AS A TREATMENT FOR REFRACTORY GLAUCOMA IN BLACK PATIENTS SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article AB Eighty-two black patients with refractory glaucoma were treated with a single-plate Molteno implant inserted in a single-stage procedure. A successful outcome (intraocular pressure less-than-or-equal-to 21 mm Hg with or without adjunctive medical therapy) was achieved in 72% of the patients with a mean follow-up of 30 months. Success was achieved in 23 (73%) of the 31 patients with open angle glaucoma, 20 (83%) of the 24 patients with either aphakic or pseudophakic glaucoma, 12 (67%) of the 18 patients with neovascular glaucoma, four (80%) of the five patients with uveitic glaucoma, and two (50%) of the four patients with congenital glaucoma. All but four patients required additional medical therapy. Visual acuities remained the same or improved in 21 (68%) of the 31 patients with open angle glaucoma, 11 (61%) of the 18 with neovascular glaucoma, 19 (79%) of the 24 patients with aphakic/pseudophakic glaucoma, three (75%) of the four patients with congenital glaucoma, and four (80%) of the five patients with uveitic glaucoma. Complications included hyphema (18%), "kissing" choroidal effusion (6%), blocked tube (8%), flat anterior chamber (12%), cataracts (5%), Tenon's cyst (encapsulated bleb) (17%), uveitis (7%), phthisis bulbi (5%), and erosion of the silicone tube (1%). C1 SUNY HLTH SCI CTR,DEPT OPHTHALMOL,BROOKLYN,NY. NIH,BETHESDA,MD 20892. NR 13 TC 56 Z9 57 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD OCT PY 1991 VL 109 IS 10 BP 1417 EP 1420 PG 4 WC Ophthalmology SC Ophthalmology GA GJ814 UT WOS:A1991GJ81400034 PM 1929932 ER PT J AU HENSON, DE AF HENSON, DE TI STUDIES ON OBSERVER VARIATION - SHOULD THE RULES BE CHANGED SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Editorial Material ID REPRODUCIBILITY; PATHOLOGY; CARCINOMA; CANCER; LUNG; VARIABILITY; DIAGNOSIS; DYSPLASIA; TUMORS; SYSTEM RP HENSON, DE (reprint author), NCI,DIV CANC PREVENT & CONTROL,EARLY DETECT BRANCH,EXECUT PLAZA N,BETHESDA,MD 20892, USA. NR 17 TC 10 Z9 10 U1 1 U2 1 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 OCT PY 1991 VL 115 IS 10 BP 991 EP 992 PG 2 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA GJ139 UT WOS:A1991GJ13900008 PM 1898246 ER PT J AU CHABNER, BA AF CHABNER, BA TI TAXOL, A TEST FOR TECHNOLOGY-TRANSFER SO BIO-TECHNOLOGY LA English DT Editorial Material RP CHABNER, BA (reprint author), NCI,DIV CANC TREATMENT,BLDG 31,ROOM 3A-52,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 0733-222X J9 BIO-TECHNOL JI Bio-Technology PD OCT PY 1991 VL 9 IS 10 BP 1012 EP 1012 DI 10.1038/nbt1091-1012 PG 1 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA HA133 UT WOS:A1991HA13300030 ER PT J AU AILENBERG, M STETLERSTEVENSON, WG FRITZ, IB AF AILENBERG, M STETLERSTEVENSON, WG FRITZ, IB TI SECRETION OF LATENT TYPE-IV PROCOLLAGENASE AND ACTIVE TYPE-IV COLLAGENASE BY TESTICULAR CELLS IN CULTURE SO BIOCHEMICAL JOURNAL LA English DT Article ID RABBIT SYNOVIAL FIBROBLASTS; FOLLICLE-STIMULATING-HORMONE; BASEMENT-MEMBRANE COLLAGEN; PERITUBULAR MYOID CELLS; SERTOLI CELLS; PLASMINOGEN-ACTIVATOR; EXTRACELLULAR-MATRIX; POLYACRYLAMIDE GELS; ENRICHED CULTURES; TISSUE INHIBITOR AB Testicular peritubular myoid cells, which have properties similar to those of vascular smooth-muscle cells, secrete a variety of metalloproteinases when maintained in culture in a chemically defined medium. The predominant metalloproteinases secreted were identified as latent type IV procollagenases having molecular masses of 72 kDa and 75 kDa, as detected in Western immunoblots with specific antibodies against type IV procollagenase. When peritubular cells were stimulated by dibutyryl cyclic AMP, forskolin or cholera toxin, they secreted increased amounts of type IV procollagenase. However, little if any of the active type IV collagenase, having a lower molecular mass of 66 kDa, could be detected under these conditions. Addition of low concentrations of cytochalasin D to peritubular cells in monoculture resulted in conversion of the latent type IV collagenase into its active form, assessed with antibody-specificity studies and by the appearance of the 66 kDa protein. In contrast, Sertoli cells in culture did not manifest an increased conversion of type IV procollagenase into type IV collagenase in the presence of cytochalasin D, even though cytochalasin D addition invariably resulted in a disruption of the microfilament assembly in each of these gonadal somatic cell populations. When peritubular cells were co-cultured with Sertoli cells, addition of cytochalasin D no longer resulted in formation of increased amounts of the active form of type IV collagenase. Sertoli cells and peritubular cells each secreted a tissue inhibitor of metalloproteinase type 2, detected with a specific antibody in a Western immunoblot to have a molecular mass of 21 kDa. We conclude that cytochalasin D acts on mesenchymal-type peritubular cells, but not on epithelial-type Sertoli cells, to enhance the conversion of latent type IV procollagenase into active type IV collagenase. This conversion of type IV procollagenase into type IV collagenase by peritubular cells was inhibited by factor(s) secreted by Sertoli cells. Interactions between Sertoli cells and peritubular cells are postulated to modulate net proteinase activities in discrete regions of the testis. C1 AFRC,INST ANIM PHYSIOL & GENET RES,DEPT MOLEC PHYSIOL,CAMBRIDGE CB2 4AT,ENGLAND. NCI,PATHOL LAB,BETHESDA,MD 20892. RP AILENBERG, M (reprint author), UNIV TORONTO,CHARLES H BEST INST,BANTING & BEST DEPT MED RES,112 COLL ST,TORONTO M5G 1L6,ONTARIO,CANADA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 47 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 OCT 1 PY 1991 VL 279 BP 75 EP 80 PN 1 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GJ369 UT WOS:A1991GJ36900010 PM 1656942 ER PT J AU GINSBURG, A ZOLKIEWSKI, M AF GINSBURG, A ZOLKIEWSKI, M TI DIFFERENTIAL SCANNING CALORIMETRY STUDY OF REVERSIBLE, PARTIAL UNFOLDING TRANSITIONS IN DODECAMERIC GLUTAMINE-SYNTHETASE FROM ESCHERICHIA-COLI SO BIOCHEMISTRY LA English DT Article ID BIOLOGICAL THERMODYNAMIC DATA; HEAT-CAPACITY DATA; BINDING-SITE; PROTEINS; STABILITY; ADENYLYLATION; CALIBRATION; TEMPERATURE; SEQUENCE; DOMAINS AB Partial unfolding of dodecameric glutamine synthetase (GS) from Escherichia coli has been studied by differential scanning calorimetry (DSC). A single endotherm (t(m) = 51.6 +/- 0.1-degrees-C and DELTA-H(cal) = 211 +/- 4 kcal/mol of enzyme) was observed in DSC experiments with Mn.GS in the presence of 1.0 mM free Mn2+ and 100 mM KCl at pH 7. The dodecameric structure of Mn.GS was retained throughout heating cycles, and thermal transitions were reversible as shown by rescans [with 6-18 mg of GS (M(r) 622000) from 15 to 68-degrees-C at 20-60-degrees-C/h] and by > 93% recovery of activity. A cooperative ratio DELTA-H(cal)/DELTA-H(vH) of 1.6 +/- 0.1 and deconvolution analysis show two cooperative units (two-state transitions): t1 = 50.4 and t2 = 51.7-degrees-C; the ratio of the relative sizes of thermally labile domains is approximately 1:2 as judged by DELTA-H-2/DELTA-H-1 congruent-to 2. However, the thermally induced overall enthalpy change (0.34 cal/g) for GS dodecamer is only 5-10% of that for thermal unfolding of small globular proteins at 50-degrees-C. The t1 and t2 values from deconvolutions of DSC data agree with t0.5 values previously calculated from spectral measurements of temperature-induced exposures of approximately 0.7 of 2 Trp and approximately 2 of 17 Tyr per subunit, respectively [Shrake et al. (1989) Biochemistry 28, 6281-6294], over a 14-degrees-C temperature range using both stabilizing and destablizing conditions for Mn.GS. No uncoupling of Trp and Tyr exposures or of cooperative units in DSC experiments with Mn.GS occurred in the presence of either 150 mM Gln (t(m) = 58.6-degrees-C) or 10 mM free [Mn2+] (t(m) = 43.9-degrees-C). Thus, cooperative interactions apparently link partial unfolding reactions of all subunits within the GS dodecamer so that only two two-state transitions are observed. RP GINSBURG, A (reprint author), NHLBI,BIOCHEM LAB,PROT CHEM SECT,BLDG 3,ROOM 208,BETHESDA,MD 20892, USA. NR 32 TC 26 Z9 26 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 1 PY 1991 VL 30 IS 39 BP 9421 EP 9429 DI 10.1021/bi00103a005 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GH408 UT WOS:A1991GH40800005 PM 1680002 ER PT J AU PITT, CG SONG, XC SIK, R CHIGNELL, CF AF PITT, CG SONG, XC SIK, R CHIGNELL, CF TI SPIN LABELS AS A PROBE OF THE MOLECULAR ENVIRONMENT OF COVALENTLY BOUND LIGANDS IN AN HYDROPHOBIC AND AN HYDROPHILIC POLYMER SO BIOMATERIALS LA English DT Article DE POLYMERS; SPIN-LABELED LIGANDS ID WATER; PARTITION; NICOTINE; SPECTRA; MODEL AB The molecular motions of spin-labelled ligands covalently bound by spacer groups to an hydrophobic and an hydrophilic polymer matrix were evaluated by ESR spectroscopy. The ligands were prepared by alkylation of 4-N-methylamino-TEMPO with the omega-bromocarboxylic esters, Br(CH2)nCOOEt, n = 1,4 and 10. The hydrolysed esters were coupled to a cross-linked aminoethylated polyacrylamide hydrogel (n = 1,4,10) and to a surface hydroxylated elastomeric polyester (n = 4). The rotational correlation times (tau-c) of the nitroxide label in the hydrogels were measured in the dry state and after exposure to water at pH 4, 7.4 and 10.5. The tau-c of the nitroxide label was insensitive to the length of the spacer group and to the degree of protonation of the tertiary amino group of the ligand. There was no evidence of self-association of the ligand and spacer, or more than a single phase within the polyacrylamide hydrogel. The tau-c of the nitroxide labelled polyester was similarly insensitive to pH, but was sensitive to organic solvents. The low mobility of the spin label and its high concentration were consistent with the spin label being covalently bound within the hydrophobic polyester matrix to a depth of at least 5-mu-m. C1 RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. AMGEN INC,THOUSAND OAKS,CA 91320. FU NIDA NIH HHS [5-RO1-DA-3616-05] NR 19 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD OCT PY 1991 VL 12 IS 8 BP 715 EP 721 DI 10.1016/0142-9612(91)90018-6 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA GN190 UT WOS:A1991GN19000002 PM 1665991 ER PT J AU SMITH, JW LONGO, DL URBA, WJ CLARK, JW WATSON, T BEVERIDGE, J CONLON, KC SZNOL, M CREEKMORE, SP ALVORD, WG LAWRENCE, JB STEIS, RG AF SMITH, JW LONGO, DL URBA, WJ CLARK, JW WATSON, T BEVERIDGE, J CONLON, KC SZNOL, M CREEKMORE, SP ALVORD, WG LAWRENCE, JB STEIS, RG TI PROLONGED, CONTINUOUS TREATMENT OF HAIRY-CELL LEUKEMIA PATIENTS WITH RECOMBINANT INTERFERON-ALPHA-2A SO BLOOD LA English DT Article ID ALPHA-2 INTERFERON; MONOCLONAL-ANTIBODIES; THERAPY; RECEPTOR; TUMOR C1 DATA MANAGEMENT SERV,FREDERICK,MD. FREDERICK MEM HOSP,FREDERICK,MD. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PATHOL,RICHMOND,VA 23298. RP SMITH, JW (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701, USA. FU NCI NIH HHS [N01-CO-74102] NR 39 TC 48 Z9 48 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 OCT 1 PY 1991 VL 78 IS 7 BP 1664 EP 1671 PG 8 WC Hematology SC Hematology GA GH251 UT WOS:A1991GH25100004 PM 1912555 ER PT J AU DUNBAR, CE SMITH, DA KIMBALL, J GARRISON, L NIENHUIS, AW YOUNG, NS AF DUNBAR, CE SMITH, DA KIMBALL, J GARRISON, L NIENHUIS, AW YOUNG, NS TI TREATMENT OF DIAMOND-BLACKFAN ANEMIA WITH HEMATOPOIETIC GROWTH-FACTORS, GRANULOCYTE-MACROPHAGE COLONY STIMULATING FACTOR AND INTERLEUKIN-3 - SUSTAINED REMISSIONS FOLLOWING IL-3 SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article ID CONGENITAL HYPOPLASTIC-ANEMIA; TYROSINE KINASE RECEPTOR; HEMATOPOIESIS; LOCUS; MOUSE; MICE; W/WV AB We have treated six transfusion-dependent, steroid-unresponsive, Diamond-Blackfan anaemia (DBA) patients with the recombinant human growth factors granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3), administered sequentially with an interim rest period. GM-CSF was given at a dose of 500-mu-g/m2/d subcutaneously for 6 weeks. Three patients increased their absolute reticulocyte counts 1.5-35-fold (mean 20-8-fold) and into the normal range, but only one showed a reduction in transfusion requirements. Between 4 and 25 weeks after discontinuation of GM-CSF, these six patients were treated with recombinant human IL-3, at doses of 60 or 125-mu-g/m2/d subcutaneously for 4-6 weeks. Three increased their absolute reticulocyte counts from 2- to 28-fold (mean 10.6-fold) and two required fewer transfusions. One of these two patients has remained transfusion independent for over a year since completion of IL-3 therapy, and the second patient required infrequent transfusions for 9 months and then became transfusion independent for the subsequent 5 months. The sustained clinical remissions seen in two of the six patients after IL-3 therapy is very encouraging and further studies in a larger cohort of DBA patients with IL-3 alone or in combination with GM-CSF or other growth factors should be carried out. C1 NHLBI,CLIN HEMATOL BRANCH,10-7C103,BETHESDA,MD 20892. IMMUNEX CORP,SEATTLE,WA. NR 24 TC 58 Z9 58 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 OCT PY 1991 VL 79 IS 2 BP 316 EP 321 DI 10.1111/j.1365-2141.1991.tb04540.x PG 6 WC Hematology SC Hematology GA GJ984 UT WOS:A1991GJ98400028 PM 1958491 ER PT J AU WEHR, TA AF WEHR, TA TI SLEEP-LOSS AS A POSSIBLE MEDIATOR OF DIVERSE CAUSES OF MANIA SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Note ID WITHDRAWAL; ANTIDEPRESSANT; HYPOMANIA AB When sleep duration and mood were monitored longitudinally in a 59-year-old woman with bipolar illness, sleep loss appeared to mediate the triggering of mania by psychosocial and pharmacological precipitating factors. This interpretation was supported by observations that mania could repeatedly be induced experimentally by depriving her of sleep for one night. The patient's data illustrate how sleep-loss might be a preventable cause of mania in a variety of situations. RP WEHR, TA (reprint author), NIMH,INTRAMURAL RES PROGRAM,CLIN PSYCHOBIOL BRANCH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 11 TC 54 Z9 55 U1 1 U2 4 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON, ENGLAND SW1X 8PG SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD OCT PY 1991 VL 159 BP 576 EP 578 DI 10.1192/bjp.159.4.576 PG 3 WC Psychiatry SC Psychiatry GA GJ989 UT WOS:A1991GJ98900023 PM 1751874 ER PT J AU SAAD, AMA HOMEIDA, M ELTOM, I NASH, T BENNETT, JL HASSAN, MA AF SAAD, AMA HOMEIDA, M ELTOM, I NASH, T BENNETT, JL HASSAN, MA TI ESOPHAGEAL-VARICES IN A REGION OF THE SUDAN ENDEMIC FOR SCHISTOSOMA-MANSONI SO BRITISH JOURNAL OF SURGERY LA English DT Article ID SYMMERS PERIPORTAL FIBROSIS AB In a field study of two villages in the Gezira, an area of the Sudan endemic for Schistosoma mansoni, liver ultrasonography was used to detect subjects with Symmer's hepatic periportal fibrosis, some of whom underwent oesophagoscopy to detect oesophageal varices. The prevalence of oesophageal varices in subjects undergoing oesophagoscopy was 54 per cent and 67 per cent respectively, occurring mainly in males aged about 30 years. The varices were usually asymptomatic. Symptomatic varices (with a positive history of haematemesis) occurred in 4 per cent and 3 per cent respectively of subjects with sonographic evidence of liver periportal fibrosis. By detecting oesophageal varices in an asymptomatic phase, hepatic ultrasonography and fibreoptic oesophagoscopy may elucidate the natural history of the varices and their response to periodic anti-schistosomal chemotherapy. C1 UNIV KHARTOUM,FAC MED,DEPT MED,KHARTOUM,SUDAN. NIH,BETHESDA,MD 20892. MICHIGAN STATE UNIV,DEPT PHARMACOL & TOXICOL,E LANSING,MI 48824. RP SAAD, AMA (reprint author), UNIV KHARTOUM,FAC MED,DEPT SURG,POB 102,KHARTOUM,SUDAN. NR 13 TC 19 Z9 20 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1323 J9 BRIT J SURG JI Br. J. Surg. PD OCT PY 1991 VL 78 IS 10 BP 1252 EP 1253 DI 10.1002/bjs.1800781033 PG 2 WC Surgery SC Surgery GA GN197 UT WOS:A1991GN19700029 PM 1958998 ER PT J AU VETTER, U EANES, ED KOPP, JB TERMINE, JD ROBEY, PG AF VETTER, U EANES, ED KOPP, JB TERMINE, JD ROBEY, PG TI CHANGES IN APATITE CRYSTAL SIZE IN BONES OF PATIENTS WITH OSTEOGENESIS IMPERFECTA SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE OSTEOGENESIS IMPERFECTA; HYDROXYAPATITE CRYSTAL SIZE; MINERAL CONTENT AB Apatite crystal size in compact bone of children (age < 11 years) and adolescents (age > 12 years) with osteogenesis imperfecta (OI) was analyzed by X-ray diffraction. Eight type I, 4 type II, 11 type III, and 14 type IV OI patients were studied along with 9 controls. The crystal size was most significantly reduced in type II patients, all of whom had died at birth. Crystal size was also diminished in both children and adolescents with types III and IV, whereas with type I OI, crystal size was reduced in children only, returning to normal in adolescence. There was a trend toward increased bone crystal size with age in both OI patients and controls. RP VETTER, U (reprint author), NIDR,BRB,BLDG 30,ROOM 106,BETHESDA,MD 20892, USA. RI Robey, Pamela/H-1429-2011; OI Robey, Pamela/0000-0002-5316-5576; Kopp, Jeffrey/0000-0001-9052-186X NR 14 TC 66 Z9 66 U1 0 U2 5 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 OCT PY 1991 VL 49 IS 4 BP 248 EP 250 DI 10.1007/BF02556213 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GF173 UT WOS:A1991GF17300006 PM 1760768 ER PT J AU REY, C RENUGOPALAKRISHNAN, V COLLINS, B GLIMCHER, MJ AF REY, C RENUGOPALAKRISHNAN, V COLLINS, B GLIMCHER, MJ TI FOURIER-TRANSFORM INFRARED SPECTROSCOPIC STUDY OF THE CARBONATE IONS IN BONE-MINERAL DURING AGING SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE CARBONATE ION; AGING; MATURATION; BONE MINERAL ID DENSITY FRACTIONATED BONE; X-RAY-DIFFRACTION; HYDROXYAPATITE FORMATION; CRYSTALLINITY; MATRIX; ENAMEL AB The environment of CO3(2-) ions in the bone mineral of chickens of different ages and in bone fractions of different density have been investigated by resolution-enhanced Fourier Transform Infrared (FTIR) Spectroscopy. Three carbonate bands appear in the upsilon-2 CO3 domain at 878, 871, and 866 cm-1, which may be assigned to three different locations of the ion in the mineral: in monovalent anionic sites of the apatitic structure (878 cm-1), in trivalent anionic sites (871 cm-1), and in unstable location (866 cm-1) probably in perturbed regions of the crystals. The distribution of the carbonate ions among these locations was estimated by comparing the intensities of the corresponding FTIR spectral bands. The intensity ratio of the 878 and 871 cm-1 bands remains remarkably constant in whole bone as well as in the fractions obtained by density centrifugation. On the contrary, the intensity ratio of the 866 cm-1 to the 871 cm-1 band was found to vary directly and decreased with the age of the animal. In bone of the same age, the relative content of the unstable carbonate ion was found to be highest in the most abundant density centrifugation fraction. A resolution factor of the CO3(2-) band (CO3 RF) was calculated from the FTIR spectra which was shown to be very sensitive to the degree of crystallinity of the mineral. The crystallinity was found to improve rapidly with the age of the animal. The CO3 RF in the bone samples obtained by density centrifugation from bone of the same animal was found to be essentially constant. This indicates a fairly homogeneous, crystalline state of the mineral phase. A comparison of the maturation characteristics of synthetic carbonated apatites with bone mineral indicates that a simple, passive, physicochemical maturation process cannot explain the changes observed in the mineral phase of whole bone tissue or in the density centrifugation fractions of bone during aging and maturation. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT ORTHOPAED SURG,STUDY SKELETAL DISORDERS & REHABIL LAB,BOSTON,MA 02115. NIEHS,DEPT MED,RES TRIANGLE PK,NC 27709. FU NIADDK NIH HHS [AM 26843]; NIAMS NIH HHS [AR 34078, AR 34081] NR 43 TC 229 Z9 237 U1 3 U2 49 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 OCT PY 1991 VL 49 IS 4 BP 251 EP 258 DI 10.1007/BF02556214 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GF173 UT WOS:A1991GF17300007 PM 1760769 ER PT J AU REY, C RENUGOPALAKRISHNAN, V SHIMIZU, M COLLINS, B GLIMCHER, MJ AF REY, C RENUGOPALAKRISHNAN, V SHIMIZU, M COLLINS, B GLIMCHER, MJ TI A RESOLUTION-ENHANCED FOURIER-TRANSFORM INFRARED SPECTROSCOPIC STUDY OF THE ENVIRONMENT OF THE CO3(2-) ION IN THE MINERAL PHASE OF ENAMEL DURING ITS FORMATION AND MATURATION SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE CARBONATE ION; AGING; MATURATION; INFRARED SPECTROSCOPY ID DENTAL ENAMEL; TOOTH ENAMEL; CARBONATE; HYDROXYAPATITE; SUBSTITUTION; CRYSTALLITES; APATITES; TEETH AB A resolution-enhanced Fourier Transform Infrared (FTIR) Spectroscopic study of the CO3(2-) ion in pig enamel of increasing age and maturity has demonstrated the existence of four different, main carbonate locations. The major CO3(2-) site arises as a result of the substitution of CO3(2-) ions in the positions occupied by PO4(3-) ions in the apatitic lattice. In addition, two minor locations have been identified in positions in which the CO3(2-) ions substitute for OH- ions. The fourth carbonate group appears to be in an unstable location. Its concentration has been found to decrease with aging and maturation, during which there is a progressive increase in the amount of mineral deposited in the enamel. The distribution of the carbonate ions in the different apatitic sites varies randomly during the formation of the mineral phase in enamel and during its maturation. Although these changes have been shown to be related to changes in the composition of the mineral phase, a comparison of the parameters assessing the degree of crystallinity of the mineral phase from upsilon-2CO3(2-) and upsilon-4PO4(3-) infrared absorption data reveals a significant discrepancy related to the nonhomogeneous partition of the CO3(2-) ion in the mineral phase. After maximum mineralization is reached, the composition of the mature mineral phase is decidedly different than that of the initial mineral deposited; the changes affect principally the concentrations of Ca2+, OH-, and HPO4(2-) ions, but not the CO3(2-) ions. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT ORTHOPAED SURG,STUDY SKELETAL DISORDERS & REHABIL LAB,BOSTON,MA 02115. NIEHS,DEPT MED,RES TRIANGLE PK,NC 27709. TSURUMI UNIV,SCH DENT MED,DEPT BIOCHEM,YOKOHAMA,KANAGAWA,JAPAN. FU NIAMS NIH HHS [AR 34078, AR 34081] NR 65 TC 116 Z9 118 U1 0 U2 13 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 OCT PY 1991 VL 49 IS 4 BP 259 EP 268 DI 10.1007/BF02556215 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GF173 UT WOS:A1991GF17300008 PM 1760770 ER PT J AU KNEPPER, MA LANKFORD, SP TERADA, Y AF KNEPPER, MA LANKFORD, SP TERADA, Y TI RENAL TUBULAR ACTIONS OF ANF SO CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT SATELLITE SYMP OF THE 13TH SCIENTIFIC MEETING OF THE INTERNATIONAL SOC OF HYPERTENSION : A DECADE OF ATRIAL NATRIURETIC FACTOR RESEARCH CY JUN 21-23, 1990 CL OTTAWA, CANADA SP INT SOC HYPERTENS DE COLLECTING DUCT; THICK ASCENDING LIMB; PROXIMAL TUBULE; NACL TRANSPORT; WATER TRANSPORT ID ATRIAL-NATRIURETIC-FACTOR; MEDULLARY COLLECTING DUCT; CYCLIC ADENOSINE-MONOPHOSPHATE; WATER REABSORPTION; GUANYLATE-CYCLASE; NEPHRON SEGMENTS; SODIUM-TRANSPORT; PROXIMAL TUBULE; ANGIOTENSIN-II; DISTAL NEPHRON AB Many of the earliest investigations of the renal effects of atrial natriuretic factor (ANF) pointed to the glomerulus as a major site of the peptide's action. More recently, there have been many reports showing various effects of ANF on renal tubular epithelia, including collecting ducts, thick ascending limbs of Henle's loop, thin limbs of Henle's loops, and proximal tubules. The purpose of this review is to summarize the evidence for renal tubular actions of ANF and analyze it from the perspective of the specialized functions of the individual nephron segments, addressing the question: can renal tubule effects of ANF play a significant role in the precise day-to-day regulation of renal NaCl and water excretion? Based on these considerations, we propose that long-term renal tubular action of ANF may be distinct from its short-term natriuretic effect. The short-term action of ANF to accelerate salt and water excretion may play a role in the overall response to acute volume overload. This action of ANF appears to be largely due to an ANF-mediated increase in glomerular filtration rate accompanied by a blunting of the tubuloglomerular feedback mechanism, perhaps with some contribution from ANF-mediated inhibition of fluid absorption in the proximal tubule. In contrast, contributions of ANF to the precise day-to-day regulation of salt and water excretion are likely to be chiefly due to ANF-mediated inhibition of NaCl and water absorption in collecting ducts, but may also involve actions of ANF on the loop of Henle. RP KNEPPER, MA (reprint author), NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BLDG 10,ROOM 6N307,BETHESDA,MD 20892, USA. NR 64 TC 28 Z9 28 U1 0 U2 1 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0008-4212 J9 CAN J PHYSIOL PHARM JI Can. J. Physiol. Pharmacol. PD OCT PY 1991 VL 69 IS 10 BP 1537 EP 1545 PG 9 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA GZ125 UT WOS:A1991GZ12500021 PM 1838023 ER PT J AU SAAVEDRA, JM KURIHARA, M AF SAAVEDRA, JM KURIHARA, M TI AUTORADIOGRAPHY OF ATRIAL-NATRIURETIC-PEPTIDE (ANP) RECEPTORS IN THE RAT-BRAIN SO CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT SATELLITE SYMP OF THE 13TH SCIENTIFIC MEETING OF THE INTERNATIONAL SOC OF HYPERTENSION : A DECADE OF ATRIAL NATRIURETIC FACTOR RESEARCH CY JUN 21-23, 1990 CL OTTAWA, CANADA SP INT SOC HYPERTENS DE QUANTITATIVE AUTORADIOGRAPHY; FLUID REGULATION; ATRIOPEPTINS; GENETIC HYPERTENSION; ATRIAL NATRIURETIC PEPTIDE BINDING SITES ID SPONTANEOUSLY HYPERTENSIVE RATS; BINDING-SITES; SALT HYPERTENSION; SUBFORNICAL ORGAN; CHOROID-PLEXUS; CYCLIC-GMP; VASOPRESSIN; LOCALIZATION; ANGIOTENSIN; POLYPEPTIDES AB Quantitative autoradiography was used to localize and characterize atrial natriuretic peptide (ANP) receptors in the rat brain and to study their regulation. Peptide receptors are selectively located to circumventricular organs outside the blood brain barrier, such as the subfornical organ, and to brain areas involved in fluid and cardiovascular regulation. Dehydration, either by water deprivation of normal rats, or chronic dehydration present in homozygous Brattleboro rats lacking vasopressin, results in large increases in ANP binding in receptor number in the subfornical organ. In the deoxycorticosterone acetate (DOCA)-salt hypertensive model, only salt treatment, but not DOCA alone or the combination of DOCA-salt, increased the ANP receptor number in the subfornical organ and the choroid plexus. Both young and adult genetically hypertensive rats have a greatly decreased ANP receptor number in the subfornical organ and the choroid plexus. Selective displacement with an inactive analog lacking the disulfide bond (ANP 111-126) suggests that genetically hypertensive rats may lack C (clearance) atrial natriuretic peptide receptors. Our results implicate brain atrial natriuretic peptide receptors in the central response to alterations in fluid regulation and blood pressure. RP SAAVEDRA, JM (reprint author), NIMH,CLIN SCI LAB,PHARMACOL SECT,9000 ROCKVILLE PIKE,BLDG 10,ROOM 2D-45,BETHESDA,MD 20892, USA. NR 39 TC 21 Z9 21 U1 0 U2 0 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0008-4212 J9 CAN J PHYSIOL PHARM JI Can. J. Physiol. Pharmacol. PD OCT PY 1991 VL 69 IS 10 BP 1567 EP 1575 PG 9 WC Pharmacology & Pharmacy; Physiology SC Pharmacology & Pharmacy; Physiology GA GZ125 UT WOS:A1991GZ12500025 PM 1663818 ER PT J AU SWEENEY, TM KIBBEY, MC ZAIN, M FRIDMAN, R KLEINMAN, HK AF SWEENEY, TM KIBBEY, MC ZAIN, M FRIDMAN, R KLEINMAN, HK TI BASEMENT-MEMBRANE AND THE SIKVAV LAMININ-DERIVED PEPTIDE PROMOTE TUMOR-GROWTH AND METASTASES SO CANCER AND METASTASIS REVIEWS LA English DT Article DE LAMININ; BASEMENT MEMBRANE; SYNTHETIC PEPTIDE; EXTRACELLULAR MATRIX; COLLAGENASE; METASTASIS ID CAPILLARY-LIKE STRUCTURES; HUMAN-ENDOTHELIAL CELLS; AMINO-ACID-SEQUENCE; SYNTHETIC POLYPEPTIDES; EXTRACELLULAR-MATRIX; BIOLOGICAL-ACTIVITY; NEURITE OUTGROWTH; HUMAN CARCINOMA; COLLAGENASE-IV; INVITRO ASSAY AB Laminin, the major glycoprotein component of basement membrane, promotes the malignant phenotype. Cells which are adherent to laminin are more malignant than the non-adherent cells and in certain tumor cells, the number of laminin receptors is positively correlated with malignancy. Laminin also increases collagenase IV activity, an enzyme demonstrated to be critical for tumor spread. A site on laminin, containing the amino acid sequence SIKVAV, has been identified which when injected intravenously with B16F10 melanoma cells, causes an increase in the number of colonies on the surface of the lungs. This peptide does not affect tumor cell arrest in the vasculature or the immune system. It does promote angiogenesis in various in vitro and in vivo models, thereby facilitating tumor cell survival. When a complex mixture of laminin-enriched basement membrane components (Matrigel) is coinjected with tumor cells subcutaneously, tumor incidence and growth increases. Various tumor cell lines and primary isolates, which previously could not form tumors in mice, can be induced to grow rapidly in the presence of Matrigel. Slowly growing tumors or arrested tumors can also be induced to grow more quickly with additional injections of Matrigel. When an SIKVAV-containing synthetic peptide is coinjected with B16F10 tumor cells and Matrigel subcutaneously in mice, larger tumors are formed than that observed with either Matrigel or cells alone. Such studies define the role of laminin in tumor growth and spread and generate new models for studying therapeutic agents. Of particular interest is the ability to grow primary isolates which generally do not grow in mice. C1 NIDR,DEV BIOL LAB,BLDG 30,ROOM 407,BETHESDA,MD 20892. MOLEC ONCOL INC,GAITHERSBURG,MD. NR 60 TC 56 Z9 57 U1 0 U2 1 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 OCT PY 1991 VL 10 IS 3 BP 245 EP 254 DI 10.1007/BF00050795 PG 10 WC Oncology SC Oncology GA GN510 UT WOS:A1991GN51000006 PM 1764767 ER PT J AU NETA, R OPPENHEIM, JJ AF NETA, R OPPENHEIM, JJ TI RADIOPROTECTION WITH CYTOKINES - LEARNING FROM NATURE TO COPE WITH RADIATION-DAMAGE SO CANCER CELLS-A MONTHLY REVIEW LA English DT Review ID TUMOR-NECROSIS-FACTOR; COLONY-STIMULATING FACTOR; GROWTH-FACTOR-BETA; BONE-MARROW CELLS; FACTOR-ALPHA; SUPEROXIDE-DISMUTASE; INTERLEUKIN-1 IL-1; IONIZING-RADIATION; ENDOTHELIAL-CELLS; PROGENITOR CELLS AB The quest for methods to protect cells from the damaging effects of ionizing radiation led to the observation that cytokines, endogenously produced hormone-like polypeptides, are radioprotective. Interleukin-1 and tumor necrosis factor-alpha, given before irradiation, can protect mice from doses of radiation that would be fatal to untreated animals. At lower doses of radiation, the hemopoietic growth factors, interleukin-1, interleukin-4, interleukin-6, tumor necrosis factor-alpha, interferon, and leukemia inhibitory factor can promote recovery when administered after irradiation. Exposure to ionizing radiation selectively induces expression of some cytokines. Recent work suggests that certain cytokines may initiate autocrine/paracrine regulated recovery and repair pathways. Thus, the radioprotective and therapeutic effects of supplementary pharmacological doses of cytokines may act by amplifying innate defenses to ionizing radiation. C1 NCI,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701. RP NETA, R (reprint author), ARMED FORCES RADIOBIOL RES INST,BETHESDA,MD 20814, USA. NR 53 TC 50 Z9 54 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1042-2196 J9 CANCER CELL-MON REV PD OCT PY 1991 VL 3 IS 10 BP 391 EP 396 PG 6 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA GL930 UT WOS:A1991GL93000003 PM 1777360 ER PT J AU TSANG, KY FINCH, MD PRIMUS, FJ SCHLOM, J AF TSANG, KY FINCH, MD PRIMUS, FJ SCHLOM, J TI HUMAN RECOMBINANT INTERLEUKIN-6 ENHANCES ANTIBODY-DEPENDENT CELLULAR CYTOTOXICITY OF HUMAN TUMOR-CELLS MEDIATED BY HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE HUMAN RIL-6; ANTIBODY-DEPENDENT CELLULAR CYTOTOXICITY; PERIPHERAL BLOOD; MONONUCLEAR CELLS ID CYTO-TOXICITY; GROWTH-FACTOR; INVITRO INDUCTION; NECROSIS FACTOR; KILLER-CELLS; T-CELLS; IL-6; CYTOKINES; INTERFERON-BETA-2; LYMPHOCYTES AB The effects of human recombinant interleukin-6 (hrIL-6) on antibody-dependent cellular cytotoxicity (ADCC) activity mediated by human peripheral blood mononuclear cells (PMNC) were investigated. Human PMNC were preincubated for 24 h with various concentrations of hrIL-6 and were used as effector cells in a 4-h Cr-51-release assay. The ability of hrIL-6 to augment ADCC was measured using anti-colorectal carcinoma mAbs D612, 17.1A and 31.1 (each directed against a distinct tumor antigen) and using three human colorectal carcinoma cell lines, LS-174T, WiDr and HT-29, as targets. A significant increase in ADCC activity was observed after PMNC were preincubated in 100-400 U/ml but not in lower concentrations of hrIL-6. Variations in activities of PMNC among donors were observed. Non-specific mAb showed no effect in augmenting ADCC activity. hrIL-6 treatment did not augment non-specific (non-mAb-mediated) cytotoxicity. The enhancement of ADCC activity was blocked by the addition of an antibody against hrIL-6 but not by an antibody to the IL-2 receptor (capable of blocking the induction of lymphokine-activated killer cell cytotoxicity by IL-2), suggesting that hrIL-6 augmentation of ADCC activity may not be mediated through IL-2. These results demonstrate that hrIL-6 augments ADCC activity of human PMNC using mAbs to human tumor antigens and human tumor cells as targets, suggesting a potential role for IL-6 in combination with anti-cancer antibodies for cancer immunotherapy. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BLDG 10,ROOM 8B07,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 38 TC 20 Z9 20 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD OCT PY 1991 VL 34 IS 1 BP 9 EP 16 DI 10.1007/BF01741318 PG 8 WC Oncology; Immunology SC Oncology; Immunology GA GK393 UT WOS:A1991GK39300002 PM 1836975 ER PT J AU CHANG, KSS LIU, WT JOSEPHS, SF AF CHANG, KSS LIU, WT JOSEPHS, SF TI REGULATION OF CELLULAR TRANSACTIVATING ACTIVITIES IN 2 DIFFERENT PROMONOCYTIC LEUKEMIA-CELL LINES SO CANCER LETTERS LA English DT Article DE TRANSACTIVATION; MONOCYTES; DIFFERENTIATION; HIV-LTR; PROMOTER ENHANCER ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; NF-KAPPA-B; TRANSCRIPTION FACTOR; BINDING PROTEIN; GENE-EXPRESSION; INFECTION; HIV; REPLICATION; PROMOTER AB Trans-activating activities of certain cellular promoter/enhancer genes may reflect the underlying mechanism for cellular differentiation. We have used two promonocytic leukemia cell lines, U937 and HL-CZ, which differ in their differentiation antigen expression. While both cell lines express CD15 antigen, only the former expresses both CD4 and CD10 antigens. These phenotypes suggest that these two cell lines appear to be arrested at different stages of differentiation. Some regions of the long terminal repeat (LTR) of human immunodeficiency virus-1 (HIV-1) contain nucleotide sequences which bind cellular trans-activating factors such as NF-kappa-B and Sp1. These sequences are also present in cellular regulatory gene sequences. The cell lines have been transfected by electroporation with a nested series of deletion mutants containing different lengths of the promoter/enhancer region for HIV-LTR. The promoter/enhancer region has been linked to a 'reporter' chloramphenicol acetyl transferase (CAT) gene. We have found that promoter/enhancer trans-activation is markedly enhanced by treating transfected cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), while similar treatment with tumor necrosis factor-alpha (TNF-alpha) slightly enhanced activation. U937 cells always showed much greater transactivating activities than did HL-CZ cells. Deletion of a negative regulatory element (NRE) from the LTR resulted in an enhanced transactivation, while deletions affecting NF-kappa-B and/or Sp1 binding sites markedly reduced transactivation. Deletion of both NRE and NRF, a second negative regulatory factor binding site, from the LTR restored the transactivation. However, in the presence of TPA, deletion of NRE sequence without concomitant deletion of the downstream NRF binding sequence was sufficient for recovering transactivation. Since these two cell lines have shown subtle differences in these responses, it may be speculated that monocytes at different stages of differentiation may respond in different ways, qualitatively and/or quantitatively, to signal transduction factors involved in the transactivation of cellular genes. C1 CHANG GUNG MED COLL,GRAD INST CLIN MED,TAOYUAN,TAIWAN. NATL YANG MING MED COLL,TAIPEI,TAIWAN. NCI,BETHESDA,MD 20892. RP CHANG, KSS (reprint author), CHANG GUNG MEM HOSP,MED RES CTR,TAOYUAN HSIEN,TAIWAN. NR 24 TC 4 Z9 4 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 OCT PY 1991 VL 60 IS 1 BP 75 EP 83 DI 10.1016/0304-3835(91)90051-I PG 9 WC Oncology SC Oncology GA GJ422 UT WOS:A1991GJ42200010 PM 1913629 ER PT J AU GORELIK, E JAY, G KIM, M HEARING, VJ DELEO, A MCCOY, JP AF GORELIK, E JAY, G KIM, M HEARING, VJ DELEO, A MCCOY, JP TI EFFECTS OF H-2KB GENE ON EXPRESSION OF MELANOMA-ASSOCIATED ANTIGEN AND LECTIN-BINDING SITES ON BL6 MELANOMA-CELLS SO CANCER RESEARCH LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I GENE; B-16 MELANOMA; H-2-ANTIGEN EXPRESSION; METASTATIC PROPERTIES; MOUSE; MHC; TRANSFECTION; GLYCOPROTEINS; ORGANIZATION AB An H-2K(b) negative BL6 melanoma clone (BL6-8) was transfected with plasmids containing either the class I H-2K(b) or class II H-21A(k) gene in combination with the neo(r) gene. The effects of the transfected genes on the expression of the melanoma-associated antigen (MAA) recognized by the monoclonal antibodies MM2-9B6 and MM2-3C6 and the cell surface carbohydrates recognized by 15 different lectins were studied. The original H-2K(b)-clone or clones transfected with neo(r) or class II H-21A(k) genes expressed high levels of MAA and very low levels of soybean agglutinin (SBA), Griffonia simplicifolia I-B4 (GSIB4), and peanut agglutinin (PNA) lectin-binding sites. In contrast, clones that expressed high levels of the transfected H-2K(b) gene completely lost the expression of MAA. In addition, these clones were characterized by the appearance of high levels of expression of the sugars specifically reacting with SBA, GSIB4, and PNA lectins. When the original BL6-8 clone was transfected with the H-2K(d) gene, 25 clones subsequently isolated had relatively low expression of the transfected H-2K(d) gene but high expression of the endogenous H-2K(b) gene accompanied by an alteration in expression of the MAA and lectin binding identical with patterns common for H-2K(b) + melanoma cells. These changes were not due to the transfection, plasmid construction, or place of insertion, since similar phenotypic characteristics were found in H-2K(b)+ but not H-2K(b)- clones isolated from the N-methyl-N'-nitro-N-nitrosoguanidine-treated BL6T2 or parental BL6 melanoma lines. In total, 73 BL6 melanoma clones were investigated and all of the 41 H-2K(b)+ clones displayed loss of MAA and appearance of SBA, GSIB4, and PNA-binding sugars. None of the 32 H-K(b)-clones showed these changes. This study indicates that the class I H-2K(b) gene product might alter several phenotypic properties of BL6 melanoma cells. The mechanisms of these changes remain unknown. We consider that these effects of the class I H-2K(b) gene are indirect, involving interactions with the B-tropic ecotropic retrovirus specific for melanomas of C57BL/6 mice origin. C1 UNIV PITTSBURGH,DEPT PATHOL,PITTSBURGH,PA 15213. AMER RED CROSS,VIROL LAB,ROCKVILLE,MD 20855. NCI,CELL BIOL LAB,BETHESDA,MD 20892. RP GORELIK, E (reprint author), UNIV PITTSBURGH,INST CANC,BIOMED SCI TOWER,W954,OHARA & DESOTO ST,PITTSBURGH,PA 15213, USA. RI Jay, Gregory/C-6346-2013 NR 38 TC 30 Z9 30 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1991 VL 51 IS 19 BP 5212 EP 5218 PG 7 WC Oncology SC Oncology GA GH250 UT WOS:A1991GH25000021 PM 1913644 ER PT J AU WESTON, A CAPORASO, NE TAGHIZADEH, K HOOVER, RN TANNENBAUM, SR SKIPPER, PL RESAU, JH TRUMP, BF HARRIS, CC AF WESTON, A CAPORASO, NE TAGHIZADEH, K HOOVER, RN TANNENBAUM, SR SKIPPER, PL RESAU, JH TRUMP, BF HARRIS, CC TI MEASUREMENT OF 4-AMINOBIPHENYL-HEMOGLOBIN ADDUCTS IN LUNG-CANCER CASES AND CONTROLS SO CANCER RESEARCH LA English DT Article ID SMALL-CELL CARCINOMA; HEMOGLOBIN ADDUCTS; CHEMICAL CARCINOGENESIS; DEBRISOQUINE METABOLISM; GENETIC PREDISPOSITION; BLADDER CARCINOGENESIS; ACETYLATION PHENOTYPE; AROMATIC-AMINES; CHROMOSOME-3; HUMANS AB Hemoglobin adducts of the activated carcinogenic aromatic amine 4-aminobiphenyl have been measured in a case-control study of lung cancer. Data obtained for lung cancer cases are compared to those obtained for controls that consisted of patients with either chronic obstructive pulmonary disease or non-pulmonary cancers. Both simple and multivariate analysis found a positive association of 4-aminobiphenyl-hemoglobin adducts with the quantity of tobacco smoked as determined by either urine cotinine or questionnaire data. No association was found between 4-aminobiphenyl-hemoglobin adducts and cancer diagnosis, and adduct levels were not related to remote tobacco use, i.e., total pack years of smoking. There was no association between the levels of adducts detected and the ability of an individual to metabolize debrisoquine (debrisoquine metabolic phenotype, CYP2D6). Whereas 4-aminobiphenyl-hemoglobin adduct levels reflected recent tobacco smoking, they were not correlated with lung cancer risk. C1 NCI,HUMAN CARCINOGENESIS LAB,ROOM 2C01,BLDG 37,BETHESDA,MD 20892. NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. MIT,WHITAKER COLL HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139. UNIV MARYLAND,DEPT PATHOL,BALTIMORE,MD 21201. NR 41 TC 22 Z9 22 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1991 VL 51 IS 19 BP 5219 EP 5223 PG 5 WC Oncology SC Oncology GA GH250 UT WOS:A1991GH25000022 PM 1913645 ER PT J AU ENOMOTO, T INOUE, M PERANTONI, AO BUZARD, GS MIKI, H TANIZAWA, O RICE, JM AF ENOMOTO, T INOUE, M PERANTONI, AO BUZARD, GS MIKI, H TANIZAWA, O RICE, JM TI K-RAS ACTIVATION IN PREMALIGNANT AND MALIGNANT EPITHELIAL LESIONS OF THE HUMAN UTERUS SO CANCER RESEARCH LA English DT Article ID POLYMERASE CHAIN-REACTION; ONCOGENE MUTATIONS; GENE-MUTATIONS; CANCER; TUMORS; TUMORIGENESIS; CARCINOMAS; VIRUS; DNA AB We previously reported (Cancer Res., 50: 6139-6145, 1990) a significant frequency of activating point mutations in codon 12 of the K-ras oncogene in endometrial adenocarcinomas of the uterine corpus (series 1). To further define the role of ras activation in the development of endometrial adenocarcinoma, we surveyed cystic, adenomatous, and atypical hyperplasias of uterine endometrium and additional cases of endometrial and cervical carcinoma (series 2) for the presence of activating mutations in cellular protooncogenes of the ras family. Polymerase chain reaction was performed from deparaffinized sections of formalin-fixed paraffin-embedded tissue. We screened for point mutations in codons 12, 13, and 61 of the K-, H-, and N-ras genes by dot blot hybridization analysis with mutation-specific oligomers. Mutations in K-ras were also confirmed by direct genomic DNA sequencing. Of 19 endometrial adenocarcinomas in series 2, point mutations in ras genes were found in 7 tumors. Six contained single-base substitutions, five in codon 12 of K-ras and one in codon 12 of N-ras. The seventh tumor contained two different point mutations in codon 12 of K-ras. In one endometrial adenocarcinoma, tumor cells with point mutations in K-ras were predominantly localized to a portion that had a more aggressive histological pattern. In endometrial hyperplasia, K-ras mutations, one in codon 12 and one in codon 13, were found in 2 of 16 hyperplasias histologically classified as atypical and clinically considered premalignant. None of 6 adenomatous hyperplasias and none of 12 cystic hyperplasias, the latter of which is considered clinically benign, contained any detectable ras mutations. No mutations in H-ras were detected in either carcinomas or hyperplastic tissue. C1 OSAKA UNIV,SCH MED,DEPT OBSTET & GYNECOL,FUKUSHIMA KU,OSAKA 553,JAPAN. KAGAWA MED SCH,DEPT PATHOL,MIKI,KAGAWA 76107,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,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 37 TC 137 Z9 140 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1991 VL 51 IS 19 BP 5308 EP 5314 PG 7 WC Oncology SC Oncology GA GH250 UT WOS:A1991GH25000036 PM 1913654 ER PT J AU SZALLASI, Z BLUMBERG, PM AF SZALLASI, Z BLUMBERG, PM TI PROSTRATIN, A NONPROMOTING PHORBOL ESTER, INHIBITS INDUCTION BY PHORBOL 12-MYRISTATE 13-ACETATE OF ORNITHINE DECARBOXYLASE, EDEMA, AND HYPERPLASIA IN CD-1 MOUSE SKIN SO CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE-C; TUMOR PROMOTION; POTENT INHIBITOR; HUMAN-PLATELETS; STAUROSPORINE; RECEPTOR; BRYOSTATIN-1; EXPRESSION; ACTIVATOR; EPIDERMIS AB Pretreatment of CD-1 mouse skin with prostratin (12-deoxyphorbol 13-acetate) inhibited biological response to phorbol 12-myristate 13-acetate. The three responses examined were hyperplasia, induction of ornithine decarboxylase, and edema; the characteristics of inhibition depended on the specific response. Hyperplasia is the best short-term correlate of tumor promotion. Two or more pretreatments with 2.56-mu-mol (1 mg) prostratin, administered at intervals of 1-4 days, almost completely blocked the hyperplasia induced by phorbol 12-myristate 13-acetate applied 15 min to 6 h after the last pretreatment. Inducibility of hyperplasia was partially restored at 2 days and recovered by 4 days. Prostratin was more potent for inhibition of ornithine decarboxylase induction (50% inhibitory dose = 25.6 nmol) than it was for hyperplasia: the inhibition was largely attained by the first application, and the recovery from inhibition was slower (8 days). Edema was partially inhibited by prostratin (dose giving 50% of maximal inhibition = 512 nmol). We have previously demonstrated that prostratin is a protein kinase C activator. Our present results show that prostratin is a functional antagonist for a class of protein kinase C mediated responses. The findings emphasize the diversity of biological outcome for protein kinase C activators, presumably driven by the extensive heterogeneity in the protein kinase C pathway. C1 NCI,MOLEC MECHANISMS TUMOR PROMOT SECT,BETHESDA,MD 20892. NR 47 TC 31 Z9 32 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1991 VL 51 IS 19 BP 5355 EP 5360 PG 6 WC Oncology SC Oncology GA GH250 UT WOS:A1991GH25000043 PM 1913657 ER PT J AU WILLEY, JC BROUSSOUD, A SLEEMI, A BENNETT, WP CERUTTI, P HARRIS, CC AF WILLEY, JC BROUSSOUD, A SLEEMI, A BENNETT, WP CERUTTI, P HARRIS, CC TI IMMORTALIZATION OF NORMAL HUMAN BRONCHIAL EPITHELIAL-CELLS BY HUMAN PAPILLOMAVIRUSES 16 OR 18 SO CANCER RESEARCH LA English DT Article ID CERVICAL-CARCINOMA; INSITU HYBRIDIZATION; HUMAN KERATINOCYTES; TYPE-16 DNA; EARLY GENES; TRANSFORMATION; CANCER; TRANSCRIPTION; SEQUENCES; PATTERNS AB Human papillomaviruses (HPV) are associated with papillomatosis of the larynx, trachea, and bronchi in decreasing order of frequency, and these papillomatosis lesions may become malignant. When the patients are not selected for a history of papillomatosis, the frequency of HPV in bronchogenic carcinoma tissue is 1-5%. In order to develop a model for investigating the role of HPV in human bronchogenic carcinogenesis, normal human bronchial epithelial cells were transfected with cloned full-length HPV16 or HPV18. Two HPV18-transformed cell lines (BEP1 and BEP2) and one HPV16-transformed cell line (BEP3) were established. These nontumorigenic epithelial cell lines have: (a) attained over 100 population doublings in vitro; (b) mutually exclusive human marker chromosomes; (c) HPV DNA in forms that are consistent with chromosomal integration by Southern analysis; (d) HPV E6, E7, and E6* mRNA transcripts by Northern and reverse transcriptase-polymerase chain reaction analysis; and (e) diminished confluence-induced squamous differentiation. These cell lines should be useful for studying mechanisms involved in proliferation, differentiation, and neoplastic transformation of human bronchial epithelial cells. C1 NCI,DIV CANC ETIOL,HUMAN CARCINOGENESIS LAB,BLDG 37,ROOM 2C05,BETHESDA,MD 20892. SWISS INST EXPTL CANC RES,DEPT CARCINOGENESIS,CH-1066 EPALINGES,SWITZERLAND. NR 42 TC 80 Z9 96 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1991 VL 51 IS 19 BP 5370 EP 5377 PG 8 WC Oncology SC Oncology GA GH250 UT WOS:A1991GH25000045 PM 1717149 ER PT J AU MICKISCH, GH LICHT, T MERLINO, GT GOTTESMAN, MM PASTAN, I AF MICKISCH, GH LICHT, T MERLINO, GT GOTTESMAN, MM PASTAN, I TI CHEMOTHERAPY AND CHEMOSENSITIZATION OF TRANSGENIC MICE WHICH EXPRESS THE HUMAN MULTIDRUG RESISTANCE GENE IN BONE-MARROW - EFFICACY, POTENCY, AND TOXICITY SO CANCER RESEARCH LA English DT Article ID RENAL-CELL CARCINOMA; P-GLYCOPROTEIN; DRUG-RESISTANCE; HUMAN CANCER; PHASE-I; VERAPAMIL; MDR1; VINBLASTINE; MECHANISMS; MODULATION AB A common form of multidrug resistance in human cancer results from expression of the MDR1 gene which encodes a plasma membrane energy-dependent multidrug efflux pump. We have engineered transgenic mice which express this multidrug transporter in their bone marrow cells and demonstrated that peripheral WBC of these animals provide a rapid and reliable system for assessing the bioactivity of agents that reverse multidrug resistance. Immunocytochemical analysis of bone marrow smears suggests that the activation of the MDR1 transgene has probably occurred at a very early stage of bone marrow differentiation since most bone marrow cells express the transporter. Expression of this transgene in bone marrow produces about 10-fold resistance to leukopenia induced by taxol compared to normal bone marrow. Chemosensitization of MDR1 mice to daunomycin and taxol, measured by a fall in WBC, is detectable at a dose as low as 0.01 mg/kg R-verapamil. A dose of 0.5 mg/kg R-verapamil reduces the WBC by nearly 50%. Chemosensitization of MDR-transgenic mice with 5 mg/kg R-verapamil, which is highly effective in reversing MDR and readily tolerated by mice, necessitates a reduction of the maximum tolerated dose of most chemotherapeutic agents by only 20%. In addition, detailed histopathological examination shows that treatment of mice with chemotherapeutic drugs and R-verapamil does not change the organ-related toxicity pattern but only moderately accentuates inherent toxic side effects of the chemotherapeutic agents. We conclude that MDR1-transgenic mice represent a valid model for evaluating efficacy, potency, and toxicity associated with chemotherapy and chemosensitization of multidrug-resistant cells in animals. C1 NCI,DIV CANC BIOL & DIAG,MOLEC BIOL LAB,BETHESDA,MD 20892. NCI,DIV CANC BIOL & DIAG,CELL BIOL LAB,BETHESDA,MD 20892. UNIV FREIBURG,DEPT HEMATOL & ONCOL,W-7800 FREIBURG,GERMANY. NR 36 TC 82 Z9 84 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1991 VL 51 IS 19 BP 5417 EP 5424 PG 8 WC Oncology SC Oncology GA GH250 UT WOS:A1991GH25000052 PM 1680550 ER PT J AU KNUDSON, A VANDEWOUDE, GF FRIEND, SH CAVENEE, WK BRODEUR, GM AF KNUDSON, A VANDEWOUDE, GF FRIEND, SH CAVENEE, WK BRODEUR, GM TI DEVELOPMENTAL GENETICS AND CHILDHOOD-CANCER - AACR SPECIAL CONFERENCE IN CANCER-RESEARCH SO CANCER RESEARCH LA English DT Editorial Material C1 MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. LUDWIG INST CANC RES,MONTREAL H3A 1A1,QUEBEC,CANADA. WASHINGTON UNIV,SCH MED,ST LOUIS,MO 63110. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701. RP KNUDSON, A (reprint author), FOX CHASE CANC INST,7701 BURHOLME AVE,PHILADELPHIA,PA 19111, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1991 VL 51 IS 19 BP 5435 EP 5439 PG 5 WC Oncology SC Oncology GA GH250 UT WOS:A1991GH25000057 PM 1655251 ER PT J AU ISOM, H KITCHINGMAN, G ROYBURMAN, P FAUSTO, N PADARATHSINGH, M AF ISOM, H KITCHINGMAN, G ROYBURMAN, P FAUSTO, N PADARATHSINGH, M TI WORKSHOP REPORT FROM THE DIVISION OF RESEARCH GRANTS, NATIONAL-INSTITUTES-OF-HEALTH - THE ROLE OF CHROMOSOME REARRANGEMENTS, DELETIONS, AND POINT MUTATIONS IN CANCER - A PATHOLOGY-B STUDY SECTION WORKSHOP SO CANCER RESEARCH LA English DT Editorial Material C1 NIH, DIV RES GRANTS, BETHESDA, MD 20892 USA. PENN STATE UNIV, MILTON S HERSHEY MED CTR, COLL MED, DEPT MICROBIOL & IMMUNOL, HERSHEY, PA 17033 USA. ST JUDE CHILDRENS RES HOSP, DEPT VIROL & MOLEC BIOL, MEMPHIS, TN 38101 USA. UNIV SO CALIF, SCH MED, DEPT PATHOL & BIOCHEM, LOS ANGELES, CA 90033 USA. BROWN UNIV, DEPT PATHOL & LAB MED, PROVIDENCE, RI 02912 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1991 VL 51 IS 19 BP 5440 EP 5444 PG 5 WC Oncology SC Oncology GA GH250 UT WOS:A1991GH25000058 PM 1913663 ER PT J AU RUSSO, P POGGI, L PARODI, S PEDRINI, AM KOHN, KW POMMIER, Y AF RUSSO, P POGGI, L PARODI, S PEDRINI, AM KOHN, KW POMMIER, Y TI PRODUCTION OF PROTEIN-ASSOCIATED DNA BREAKS BY 8-METHOXYCAFFEINE, CAFFEINE AND 8-CHLOROCAFFEINE IN ISOLATED-NUCLEI FROM L1210 CELLS - COMPARISON WITH THOSE PRODUCED BY TOPOISOMERASE-II INHIBITORS SO CARCINOGENESIS LA English DT Article ID CHINESE-HAMSTER CELLS; SISTER CHROMATID EXCHANGES; MAMMALIAN-CELLS; STRAND CLEAVAGE; CYTO-TOXICITY; POSTREPLICATION REPAIR; INTERCALATING AGENTS; REUNION REACTION; DAMAGE; DERIVATIVES AB 8-Methoxycaffeine (8-MOC) is a caffeine derivative, more potent than the parent compound, but very similar to caffeine in terms of induction of DNA single-strand breaks (SSBs), DNA double-strand breaks (DSBs) and DNA-protein crosslinks (DPCs). We have studied the capability of 8-MOC, caffeine and 8-chlorocaffeine (8-CC) of inducing SSBs, DSBs and DPCs, and we have compared 8-MOC with ellipticine, a typical inhibitor of DNA topoisomerase II. The DNA effects of 8-MOC appeared similar to those of ellipticine. In both cases SSBs, DSBs and DPCs were present in a similar ratio, and they were rapidly reversible after removal of the drug. The dose-response curve was bell-shaped for both compounds. In addition, 8-MOC, caffeine and 8-CC were capable of inhibiting DSBs induced by ellipticine. These results were obtained at the level of L1210 cell nuclei. In spite of these functional similarities, 8-MOC, caffeine and 8-CC were unable to stimulate the formation of a cleavable complex by purified 1,1210 topoisomerase II (p170 form) when SV40 DNA and human c-myc DNA were used as substrate. These methylated oxypurines could be active on a different form of topoisomerase II, or, alternatively, they could be active only in the natural chromatin 'milieu' within the nucleus. C1 UNIV GENOA,DEPT ONCOL,I-16126 GENOA,ITALY. CNR,IST GENET BIOCHIM & EVOLUZ,I-27100 PAVIA,ITALY. NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RP RUSSO, P (reprint author), IST NAZL RIC CANC,VIALE BENEDETTO XV 10,I-16132 GENOA,ITALY. NR 41 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 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 1991 VL 12 IS 10 BP 1781 EP 1790 DI 10.1093/carcin/12.10.1781 PG 10 WC Oncology SC Oncology GA GK259 UT WOS:A1991GK25900005 PM 1657426 ER PT J AU LOH, YP ANDREASSON, KI BIRCH, NP AF LOH, YP ANDREASSON, KI BIRCH, NP TI INTRACELLULAR TRAFFICKING AND PROCESSING OF PROOPIOMELANOCORTIN SO CELL BIOPHYSICS LA English DT Article; Proceedings Paper CT ANNUAL A N RICHARDS SYMP ON CELLULAR MECHANISMS OF PROTEIN SORTING AND PROCESSING / THE 1990 CONVENTION OF THE PHYSIOLOGICAL SOC OF PHILADELPHIA CY MAY 09-10, 1990 CL PHILADELPHIA, PA SP PHYSIOL SOC PHILADELPHIA, HAHNEMANN UNIV, UNIV SO CALIF ID PITUITARY INTERMEDIATE LOBE; BETA-LIPOTROPIN; SECRETORY GRANULES; ANTERIOR-PITUITARY; CONVERTING ENZYME; TUMOR CELLS; ACTH; ENDORPHIN; TRANSPORT; YEAST C1 HOWARD HUGHES MED INST,BETHESDA,MD 20892. RP LOH, YP (reprint author), NICHHD,DEV NEUROBIOL LAB,CELLULAR NEUROBIOL SECT,BETHESDA,MD 20892, USA. RI Birch, Nigel/H-2498-2011 OI Birch, Nigel/0000-0002-8417-3587 NR 34 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0163-4992 J9 CELL BIOPHYS JI Cell Biophys. PD OCT-DEC PY 1991 VL 19 IS 1-3 BP 73 EP 83 PG 11 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA KA656 UT WOS:A1991KA65600009 PM 1726890 ER PT J AU SZABO, E PREIS, LH BROWN, PH BIRRER, MJ AF SZABO, E PREIS, LH BROWN, PH BIRRER, MJ TI THE ROLE OF JUN AND FOS GENE FAMILY MEMBERS IN 12-O-TETRADECANOYLPHORBOL-13-ACETATE INDUCED HEMATOPOIETIC DIFFERENTIATION SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID HUMAN MONOCYTIC DIFFERENTIATION; PROMYELOCYTIC LEUKEMIA-CELLS; TRANSCRIPTION FACTOR AP-1; PROTO-ONCOGENE FOS; C-JUN; RIBONUCLEIC-ACID; RAPID INDUCTION; GROWTH-FACTORS; EXPRESSION; ACTIVATION AB Terminal differentiation of the leukemic cell lines U-937 and HL-60 by 12-O-tetradecanoylphorbol-13-acetate is accompanied by marked changes in gene expression. In this study, we demonstrate that the expression of jun and fos gene family members is induced with variable kinetics during 12-O-tetradecanoylphorbol-13-acetate induced differentiation, with c-jun expression best paralleling differentiation. The generation of AP-1 complexes, as measured by DNA binding activity, closely parallels morphological differentiation. Furthermore, the ability of these complexes to regulate gene expression is demonstrated by increased transcription from an AP-1 driven reporter construct and marked increases in the expression of endogenous AP-1 regulated genes. Differentiation assays using water soluble phorbol esters reveal that differentiation becomes irreversible soon after AP-1 appears. This tight correlation between c-jun expression, the generation of AP-1 activity, and differentiation suggests a critical role for this gene and transcriptional complex during this process. C1 USN HOSP,NCI,MED ONCOL BRANCH,BLDG 8,ROOM 5101,BETHESDA,MD 20814. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. NR 47 TC 78 Z9 78 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD OCT PY 1991 VL 2 IS 10 BP 475 EP 482 PG 8 WC Cell Biology SC Cell Biology GA GN381 UT WOS:A1991GN38100001 PM 1751404 ER PT J AU GAETANO, C MATSUMOTO, K THIELE, CJ AF GAETANO, C MATSUMOTO, K THIELE, CJ TI RETINOIC ACID NEGATIVELY REGULATES P34CDC2 EXPRESSION DURING HUMAN NEUROBLASTOMA-DIFFERENTIATION SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID HUMAN NEURO-BLASTOMA; CDC2 PROTEIN-KINASE; RETINOBLASTOMA GENE-PRODUCT; CELL-CYCLE ARREST; HISTONE-H1 KINASE; PHOSPHORYLATION; MITOSIS; LINES; INVITRO; GROWTH AB p34cdc2 is a protein kinase that has an important role in controlling cell cycle progression and may regulate tumor suppressor gene activity. In this work, we show that the arrest of cell growth and induction of differentiation in a tumorigenic neuroblastoma cell line by retinoic acid (RA) is associated with a 75-fold decrease in the level of p34cdc2 protein. The RA induced decrease in p34cdc2 levels does not simply reflect the arrest of cell growth, because p34cdc2 levels are not reduced when neuroblastoma cells are growth arrested by nutrient deprivation. Furthermore, dephosphorylation of the tumor suppressor gene product RB, a substrate for the p34cdc2 kinase activity, is observed only when p34cdc2 levels are decreased in RA treated cells. These studies link regulation of cdc2 level, RB phosphorylation state, and induction of differentiation by RA and suggest that alterations in the cdc2 gene or in genes controlling its regulation contribute to tumorigenesis. C1 NCI,PEDIAT BRANCH,MOLEC GENET SECT,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. OI Gaetano, Carlo/0000-0002-5238-1832 NR 48 TC 44 Z9 44 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 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD OCT PY 1991 VL 2 IS 10 BP 487 EP 493 PG 7 WC Cell Biology SC Cell Biology GA GN381 UT WOS:A1991GN38100003 PM 1751405 ER PT J AU HOCHMAN, N HOJO, H HOJO, S CORCORAN, ML ALLEN, JB HANSEN, CT WAHL, SM WAHL, LM AF HOCHMAN, N HOJO, H HOJO, S CORCORAN, ML ALLEN, JB HANSEN, CT WAHL, SM WAHL, LM TI REVERSAL OF IMMUNE DYSFUNCTION IN OSTEOPETROTIC RATS BY INTERFERON-GAMMA - AUGMENTATION OF MACROPHAGE IA EXPRESSION AND LYMPHOCYTE INTERLEUKIN-2 PRODUCTION AND PROLIFERATION SO CELLULAR IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; OSTEOCLAST-ACTIVATING FACTOR; OP OP MOUSE; BONE-RESORPTION; ACCESSORY CELL; T-LYMPHOCYTES; SPLEEN-CELLS; MARROW; GROWTH; MICE C1 NIDR,CELLULAR IMMUNOL SECT,IMMUNOL LAB,BETHESDA,MD 20892. NIH,DIV RES SERV,VET RESOURCES BRANCH,BETHESDA,MD 20892. NR 26 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD OCT 1 PY 1991 VL 137 IS 1 BP 14 EP 23 DI 10.1016/0008-8749(91)90052-D PG 10 WC Cell Biology; Immunology SC Cell Biology; Immunology GA GE773 UT WOS:A1991GE77300002 PM 1909214 ER PT J AU LASZLO, G DICKLER, HB AF LASZLO, G DICKLER, HB TI ALTERATIONS OF LYMPHOCYTE-B FC-GAMMA-R-II EXPRESSION AND LIGAND-BINDING CAPACITY INDUCED BY VARIOUS ACTIVATORS SO CELLULAR IMMUNOLOGY LA English DT Article ID CELL GROWTH-FACTOR; CROSS-LINKING; SURFACE-IMMUNOGLOBULIN; INHIBIT INDUCTION; ANTIGEN RECEPTORS; PROTEIN-SYNTHESIS; ANTIBODIES; DIFFERENTIATION; MOLECULES; OCCUPANCY C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NR 31 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD OCT 1 PY 1991 VL 137 IS 1 BP 24 EP 35 DI 10.1016/0008-8749(91)90053-E PG 12 WC Cell Biology; Immunology SC Cell Biology; Immunology GA GE773 UT WOS:A1991GE77300003 PM 1653115 ER PT J AU SCHAUF, V HOLOBAUGH, P MILLER, P MITTAL, K AF SCHAUF, V HOLOBAUGH, P MILLER, P MITTAL, K TI SENSITIZATION INVITRO OF HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS TO PHENOLIC GLYCOLIPID-1 OF MYCOBACTERIUM-LEPRAE IN LIPOSOMES SO CELLULAR IMMUNOLOGY LA English DT Article ID TUBERCULOID LEPROSY; GENETIC-CONTROL; HLA; LYMPHOCYTES; RESPONSES; KLH C1 ARMED FORCES RADIOBIOL RES INST,BETHESDA,MD 20814. NASSAU CTY MED CTR,DEPT PEDIAT,E MEADOW,NY 11554. NIH,BETHESDA,MD 20892. RP SCHAUF, V (reprint author), SUNY STONY BROOK,SCH MED,DEPT AIME COTTON,STONY BROOK,NY 11794, USA. NR 22 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD OCT 1 PY 1991 VL 137 IS 1 BP 81 EP 87 DI 10.1016/0008-8749(91)90058-J PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA GE773 UT WOS:A1991GE77300008 PM 1884400 ER PT J AU HOLLENBERG, SM CUNNION, RE PARRILLO, JE AF HOLLENBERG, SM CUNNION, RE PARRILLO, JE TI THE EFFECT OF TUMOR-NECROSIS-FACTOR ON VASCULAR SMOOTH-MUSCLE - INVITRO STUDIES USING RAT AORTIC RINGS SO CHEST LA English DT Article ID HUMAN SEPTIC SHOCK; INTERLEUKIN-1; ENDOTOXIN; CONTRACTILITY; CACHECTIN; HYPOTENSION; ASSOCIATION; DEPRESSION; RABBITS; SEPSIS AB The mechanisms of vasodilation in septic shock have not been well elucidated. We used isolated rat aortic rings as an in vitro model of vascular reactivity to assess the acute, direct effects on vascular smooth muscle relaxation of four cytokines: interleukin 1 (IL-1), interleukin 2 (IL-2), interleukin 6 (IL-6), and tumor necrosis factor (TNF). The rings were precontracted with catecholamines and then test cytokines were added. The changes in tension with IL-1 at 1,000 U/ml, IL-2 at 1,000 U/ml, and IL-6 at 500 U/ml differed from controls by -67 +/- 59, -5 +/- 42, and 8 +/- 56 mg/mg of tissue, respectively (for each, n = 10, p = NS). The change in tension with TNF at 1,000 U/ml differed from controls by -176 +/- 42 mg/mg of tissue (n = 20, p < 0.001). Chemical removal of the endothelium with deoxycholate diminished TNF-induced vasodilation to -62 +/- 14 mg/mg of tissue (p < 0.05). The relaxation with TNF occurred in a concentration-dependent fashion and was unaffected by indomethacin. This study demonstrates that TNF has an acute, concentration-dependent, cyclooxygenase-independent, vasodilatory effect on vascular smooth muscle. The effect of TNF was partially, but not fully, dependent on the presence of an intact endothelium, implying that TNF acts on both the endothelium and the smooth muscle. These findings suggest that TNF may play an important role in the vasodilation characteristic of septic shock. C1 NIH,CTR CLIN,DEPT CRIT CARE MED,BETHESDA,MD 20892. NR 27 TC 57 Z9 61 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD OCT PY 1991 VL 100 IS 4 BP 1133 EP 1137 DI 10.1378/chest.100.4.1133 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA GK147 UT WOS:A1991GK14700054 PM 1914573 ER PT J AU BONOW, RO LAKATOS, E MARON, BJ EPSTEIN, SE AF BONOW, RO LAKATOS, E MARON, BJ EPSTEIN, SE TI SERIAL LONG-TERM ASSESSMENT OF THE NATURAL-HISTORY OF ASYMPTOMATIC PATIENTS WITH CHRONIC AORTIC REGURGITATION AND NORMAL LEFT-VENTRICULAR SYSTOLIC FUNCTION SO CIRCULATION LA English DT Article DE AORTIC REGURGITATION; LEFT VENTRICULAR FUNCTION; ECHOCARDIOGRAPHY; RADIONUCLIDE ANGIOGRAPHY ID VALVE-REPLACEMENT; AFTERLOAD MISMATCH; EJECTION FRACTION; PRELOAD RESERVE; LATE SURVIVAL; EXERCISE; INSUFFICIENCY; DISEASE; PREDICTOR AB Background. Many asymptomatic patients with aortic regurgitation and normal left ventricular systolic function remain clinically stable for many years, but others ultimately develop symptoms or left ventricular dysfunction and require operation. To identify indexes of left ventricular function predictive of symptomatic and functional deterioration during the long-term course of asymptomatic patients, we studied 104 asymptomatic patients with chronic severe aortic regurgitation and normal left ventricular ejection fraction at rest. Methods and Results. Serial echocardiographic (average, 7.8 per patient) and radionuclide angiographic (average, 5.0 per patient) studies were obtained over a mean follow-up period of 8 years (range, 2-16 years). By Kaplan-Meier life table analysis, 58 +/- 9% of patients remained asymptomatic with normal ejection fraction at 11 years, an average attrition rate of less than 5% per year; two patients died suddenly, four developed asymptomatic left ventricular dysfunction, and 19 underwent operation because symptoms developed. By univariate Cox regression analysis, many variables on initial study were associated with death, ventricular dysfunction, or symptoms, including age, left ventricular end-systolic dimension and end-diastolic dimension, fractional shortening, and both rest and exercise ejection fraction (all p < 0.001). The average rates of change of rest ejection fraction, fractional shortening, and end-systolic dimension were also associated with death or symptoms by univariate Cox analysis (all p < 0.01). However, when all variables were included in a multivariate Cox analysis, only age (p < 0.05), initial end-systolic dimension (p < 0.001), and rate of change in end-systolic dimension and rest ejection fraction during serial studies (both p < 0.05) predicted outcome. Conclusions. Thus, in addition to indexes of left ventricular function determined on initial evaluation, serial long-term changes in systolic function identify patients likely to develop symptoms and require operation. Patients have a higher risk of symptomatic deterioration if there is progressive change in end-systolic dimension or resting ejection fraction during the course of serial studies. RP BONOW, RO (reprint author), NHLBI, CARDIOL BRANCH, BLDG 10, ROOM 7B-15, BETHESDA, MD 20892 USA. NR 28 TC 241 Z9 248 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD OCT PY 1991 VL 84 IS 4 BP 1625 EP 1635 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA GJ692 UT WOS:A1991GJ69200019 PM 1914102 ER PT J AU GROSSMAN, E CHANG, PC HOFFMAN, A TAMRAT, M GOLDSTEIN, DS AF GROSSMAN, E CHANG, PC HOFFMAN, A TAMRAT, M GOLDSTEIN, DS TI EVIDENCE FOR FUNCTIONAL ALPHA-2-ADRENOCEPTORS ON VASCULAR SYMPATHETIC-NERVE ENDINGS IN THE HUMAN FOREARM SO CIRCULATION RESEARCH LA English DT Article DE ADRENOCEPTORS; SYMPATHETIC NERVOUS SYSTEM; NOREPINEPHRINE; YOHIMBINE; METHOXAMINE; EPINEPHRINE; PROPRANOLOL; NITROPRUSSIDE; TRIMETHAPHAN ID PRESYNAPTIC ALPHA-ADRENOCEPTORS; NORADRENALINE RELEASE; TRANSMITTER RELEASE; VASOCONSTRICTION; NOREPINEPHRINE; MODULATION; VESSELS; CATECHOLAMINES; ANTAGONISTS; INHIBITION AB The role of alpha-2-adrenoceptors on vascular sympathetic nerve endings in modulating release of the sympathetic neurotransmitter norepinephrine (NE) in humans was examined by measuring the regional rate of appearance of NE in forearm venous plasma (forearm NE spillover [FSO]) in 32 healthy volunteers during intra-arterial infusion of drugs acting at adrenoceptors or directly on vascular smooth muscle. Simultaneous intra-arterial infusions of tracer amounts of [H-3]NE were used to calculate the extraction rate of NE in the forearm. Methoxamine or propranolol with epinephrine (PRO+EPI) was used to stimulate alpha-adrenoceptors, yohimbine was used to inhibit alpha-adrenoceptors, and sodium nitroprusside (NIP) was used to produce increases in forearm blood flow directly. Sympathetic efferent activity was manipulated by systemic intravenous infusions of NIP or trimethaphan. Yohimbine and NIP increased and PRO+EPI and methoxamine decreased NE FSO, without effects on systemic blood pressure, heart rate, or arterial levels of catechols. Changes in FSO were flow dependent; therefore, the slope of the relation between the changes in FSO and forearm blood flow was used to evaluate the effects of each drug on regional sympathoneural activity. During administration of yohimbine, the mean slope of the relation between the change in estimated FSO and the change in forearm blood flow was about four times that of the mean slope during administration of NIP (F = 6.35, p < 0.05). The slopes of the relations between changes in FSO and forearm blood flow were unaffected by systemic trimethaphan or NIP infusion, indicating that the activity of alpha-2-adrenoceptors was not altered during inhibition or reflective stimulation of sympathetic outflow. The results suggest that alpha-2-adrenoceptors modulate release of NE from vascular sympathetic nerve endings in humans and that the function of these receptors is unchanged during acute changes in junctional NE concentrations. C1 NINCDS,CLIN NEUROSCI BRANCH,BLDG 10,ROOM 5N214,BETHESDA,MD 20892. NHLBI,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20892. NR 32 TC 22 Z9 22 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD OCT PY 1991 VL 69 IS 4 BP 887 EP 897 PG 11 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA GH857 UT WOS:A1991GH85700001 PM 1657439 ER PT J AU SHALABY, MR HALGUNSET, J HAUGEN, OA AARSET, H AARDEN, L WAAGE, A MATSUSHIMA, K KVITHYLL, H BORASCHI, D LAMVIK, J ESPEVIK, T AF SHALABY, MR HALGUNSET, J HAUGEN, OA AARSET, H AARDEN, L WAAGE, A MATSUSHIMA, K KVITHYLL, H BORASCHI, D LAMVIK, J ESPEVIK, T TI CYTOKINE-ASSOCIATED TISSUE-INJURY AND LETHALITY IN MICE - A COMPARATIVE-STUDY SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article ID TUMOR NECROSIS FACTOR; ARACHIDONIC-ACID METABOLISM; HUMAN DERMAL FIBROBLASTS; FACTOR-ALPHA; ENDOTOXIN-SHOCK; INTERLEUKIN-1; INVIVO; EXPRESSION; INDUCTION; CLONING C1 UNIV TRONDHEIM,INST CANE RES,N-7006 TRONDHEIM,NORWAY. UNIV AMSTERDAM,CENT LAB NETHERLANDS,AMSTERDAM,NETHERLANDS. NCI,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21701. SCLAVO RES CTR,IMMUNOPHARMACOL LAB,SIENA,ITALY. RI Waage, Anders/D-7705-2013 NR 35 TC 27 Z9 27 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD OCT PY 1991 VL 61 IS 1 BP 69 EP 82 DI 10.1016/S0090-1229(06)80008-5 PG 14 WC Immunology; Pathology SC Immunology; Pathology GA GG536 UT WOS:A1991GG53600006 PM 1959240 ER PT J AU KALER, SG GOLDSTEIN, DS HOLMES, C GAHL, WA AF KALER, SG GOLDSTEIN, DS HOLMES, C GAHL, WA TI NEUROCHEMICAL EVIDENCE OF DOPAMINE-BETA-HYDROXYLASE DEFICIENCY IN MENKES DISEASE SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 NICHHD,HUMAN GENET BRANCH,BETHESDA,MD. NINCDS,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD OCT PY 1991 VL 39 IS 3 BP A667 EP A667 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA GF369 UT WOS:A1991GF36900047 ER PT J AU QUEZADO, Z WILSON, WH PARKER, MM CUNNION, RE REDA, D BRYANT, G OGNIBENE, FP AF QUEZADO, Z WILSON, WH PARKER, MM CUNNION, RE REDA, D BRYANT, G OGNIBENE, FP TI HIGH-DOSE IFOSFAMIDE (IFF) CHEMOTHERAPY IS ASSOCIATED WITH SEVERE, REVERSIBLE CARDIAC DYSFUNCTION SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 CC,DEPT CRIT CARE,BETHESDA,MD. NCI,BETHESDA,MD 20892. RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD OCT PY 1991 VL 39 IS 3 BP A667 EP A667 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA GF369 UT WOS:A1991GF36900051 ER PT J AU RILEY, ML SCHWIETERMAN, WD KURMAN, CC MAGRATH, IT BHATIA, K NELSON, DL AF RILEY, ML SCHWIETERMAN, WD KURMAN, CC MAGRATH, IT BHATIA, K NELSON, DL TI MOLECULAR GENETIC-ANALYSIS OF A LYMPHOMA OCCURRING IN A PATIENT WITH INTESTINAL LYMPHANGIECTASIA SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD OCT PY 1991 VL 39 IS 3 BP A667 EP A667 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA GF369 UT WOS:A1991GF36900050 ER PT J AU MILLER, W BARR, J RUDD, KE AF MILLER, W BARR, J RUDD, KE TI IMPROVED ALGORITHMS FOR SEARCHING RESTRICTION MAPS SO COMPUTER APPLICATIONS IN THE BIOSCIENCES LA English DT Article ID ESCHERICHIA-COLI K-12; PRIORITY-QUEUE; DNA-SEQUENCES; CHROMOSOME AB We present algorithms for searching a DNA restriction enzyme map for a region that best matches a shorter 'probe' map. Our algorithms utilize a new model of map alignments, and extensive experiments prove our model superior to earlier approaches for certain applications. Let M be the number of map sites and P be the number of probe sites. Our first algorithm, which optimizes only over a restricted class of alignments, requires O(MP log P) worst-case time and O(M + P) space. Our second algorithm, which optimizes over all alignments, runs in O(MP3) time and O(M + P2) space, under reasonable assumptions about the distribution of restriction enzyme cleavage sites. Combining the algorithms gives a map-searching method that optimizes over all alignments in O(MP log P) time in practice. The algorithms' effectiveness is illustrated by searches involving a genomic restriction map of Escherichia coli. C1 NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. RP MILLER, W (reprint author), PENN STATE UNIV,DEPT COMP SCI,UNIVERSITY PK,PA 16802, USA. FU NLM NIH HHS [R01 LM5110] NR 16 TC 6 Z9 6 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0266-7061 J9 COMPUT APPL BIOSCI JI Comput. Appl. Biosci. PD OCT PY 1991 VL 7 IS 4 BP 447 EP 456 PG 10 WC Computer Science, Interdisciplinary Applications SC Computer Science GA GL145 UT WOS:A1991GL14500003 PM 1747775 ER PT J AU BERGER, MP MUNSON, PJ AF BERGER, MP MUNSON, PJ TI A NOVEL RANDOMIZED ITERATIVE STRATEGY FOR ALIGNING MULTIPLE PROTEIN SEQUENCES SO COMPUTER APPLICATIONS IN THE BIOSCIENCES LA English DT Article ID ALIGNMENT; ALGORITHM; TREES AB The rigorous alignment of multiple protein sequences becomes impractical even with a modest number of sequences, since computer memory and time requirements increase as the product of the lengths of the sequences. We have devised a strategy to approach such an optimal alignment, which modifies the intensive computer storage and time requirements of dynamic programming. Our algorithm randomly divides a group of unaligned sequences into two subgroups, between which an optimal alignment is then obtained by a Needleman-Wunsch style of algorithm. Our algorithm uses a matrix with dimensions corresponding to the lengths of the two aligned sequence subgroups. The pairwise alignment process is repeated using different random divisions of the whole group into two subgroups. Compared with the rigorous approach of solving the n-dimensional lattice by dynamic programming, our iterative algorithm results in alignments that match or are close to the optimal solution, on a limited set of test problems. We have implemented this algorithm in a computer program that runs on the IBM PC class of machines, together with a user-friendly environment for interactively selecting sequences or groups of sequences to be aligned either simultaneously or progressively. C1 NIH, DIV COMP RES & TECHNOL,ANALYT BIOSTAT SECT, BLDG 12A,ROOM 2009, BETHESDA, MD 20892 USA. NATL INST CHILD HLTH, THEORET & PHYS BIOL LAB, BETHESDA, MD 20892 USA. NR 23 TC 68 Z9 69 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0266-7061 J9 COMPUT APPL BIOSCI JI Comput. Appl. Biosci. PD OCT PY 1991 VL 7 IS 4 BP 479 EP 484 PG 6 WC Computer Science, Interdisciplinary Applications SC Computer Science GA GL145 UT WOS:A1991GL14500007 PM 1747779 ER PT J AU ROSSOUW, JE RIFKIND, BM AF ROSSOUW, JE RIFKIND, BM TI CONTRIBUTION OF HIGH SERUM-CHOLESTEROL TO PROGRESSION OF CORONARY ATHEROSCLEROSIS AND SUBSEQUENT CLINICAL EVENTS IN PATIENTS WITH CORONARY HEART-DISEASE SO CORONARY ARTERY DISEASE LA English DT Review DE CHOLESTEROL; CORONARY DISEASE; MYOCARDIAL INFARCTION; HYPERCHOLESTEROLEMIA; PROSPECTIVE STUDIES; RISK FACTORS; HUMAN ID MYOCARDIAL-INFARCTION; ARTERY DISEASE; RISK-FACTORS RP ROSSOUW, JE (reprint author), NHLBI,DIV HEART & VASC DIS,LIPID METAB ATHEROGENESIS BRANCH,BETHESDA,MD 20851, USA. NR 12 TC 3 Z9 3 U1 0 U2 1 PU CURRENT SCIENCE PI PHILADELPHIA PA 400 MARKET STREET,SUITE 750 ATTN:SARAH WHEALEN/SUB MGR, PHILADELPHIA, PA 19106 SN 0954-6928 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD OCT PY 1991 VL 2 IS 8 BP 870 EP 874 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA GQ131 UT WOS:A1991GQ13100002 ER PT J AU AGARWAL, VR SATO, SM AF AGARWAL, VR SATO, SM TI XLPOU 1 AND XLPOU 2, 2 NOVEL POU DOMAIN GENES EXPRESSED IN THE DORSOANTERIOR REGION OF XENOPUS EMBRYOS SO DEVELOPMENTAL BIOLOGY LA English DT Article ID CELL-SPECIFIC EXPRESSION; TRANSCRIPTION FACTOR; HOMEOBOX GENE; C-ELEGANS; SYNERGISTIC INTERACTIONS; CAENORHABDITIS-ELEGANS; POSTERIOR EXPRESSION; PATTERN-FORMATION; NEURAL INDUCTION; GROWTH-HORMONE C1 NATL INST DIABET & DIGEST & KIDNEY DIS,CLIN ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 59 TC 47 Z9 49 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD OCT PY 1991 VL 147 IS 2 BP 363 EP 373 DI 10.1016/0012-1606(91)90294-D PG 11 WC Developmental Biology SC Developmental Biology GA GG610 UT WOS:A1991GG61000009 PM 1717323 ER PT J AU MCCALEB, ML MCKEAN, ML HOHMAN, TC LAVER, N ROBISON, WG AF MCCALEB, ML MCKEAN, ML HOHMAN, TC LAVER, N ROBISON, WG TI INTERVENTION WITH THE ALDOSE REDUCTASE INHIBITOR, TOLRESTAT, IN RENAL AND RETINAL LESIONS OF STREPTOZOTOCIN-DIABETIC RATS SO DIABETOLOGIA LA English DT Article DE NEPHROPATHY; RETINOPATHY; DIABETIC COMPLICATIONS; ALDOSE REDUCTASE ID URINARY ALBUMIN EXCRETION; PREVENTION; MELLITUS; RETINOPATHY; CAPILLARIES; SORBINIL; MICROALBUMINURIA; ABNORMALITIES; NEPHROPATHY AB The progressive increase in urinary albumin excretion, which precedes the development of diabetic nephropathy, can be prevented in diabetic rats if the aldose reductase inhibitor, tolrestat, is administered at the initiation and throughout the duration of hyperglycaemia. We therefore determined the ability of tolrestat to intervene in the further progression of already established urinary albumin excretion of streptozotocin-diabetic female Wistar rats. Two months after streptozotocin injection, diabetic rats were grouped as low-urinary albumin excretion (0.2-1.0 mg albumin/day) or high-urinary albumin excretion (1.9-5.9 mg albumin/day), at which time tolrestat intervention (25 mg/kg per day) was begun for half of the diabetic rats in each urinary albumin excretion group. After six months of treatment tolrestat caused a significant reduction in the urinary albumin excretion rate of the low-urinary albumin excretion group only. The diabetes-induced rise of total urinary protein in both groups was significantly reduced by tolrestat. Furthermore, the diabetes-induced increase (49%) in the thickness of the basement membranes of retinal capillaries from the outer plexiform layer was significantly diminished by tolrestat administration. In conclusion, intervention therapy with the aldose reductase inhibitor, tolrestat, can reduce the progression of urinary albumin excretion and retinal basement membrane thickening in long-term diabetic rats. C1 NEI,BETHESDA,MD 20892. RP MCCALEB, ML (reprint author), WYETH AYERS RES,CN 8000,PRINCETON,NJ 08543, USA. NR 41 TC 37 Z9 40 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD OCT PY 1991 VL 34 IS 10 BP 695 EP 701 DI 10.1007/BF00401513 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GM085 UT WOS:A1991GM08500002 PM 1959701 ER PT J AU GUZMAN, K MILLER, CD PHILLIPS, CL MILLER, WL AF GUZMAN, K MILLER, CD PHILLIPS, CL MILLER, WL TI THE GENE ENCODING OVINE FOLLICLE-STIMULATING HORMONE-BETA - ISOLATION, CHARACTERIZATION, AND COMPARISON TO A RELATED OVINE GENOMIC SEQUENCE SO DNA AND CELL BIOLOGY LA English DT Article ID HUMAN CHORIONIC-GONADOTROPIN; AMINO-ACID SEQUENCE; LUTEINIZING-HORMONE; GLUCOCORTICOID RECEPTOR; NUCLEOTIDE-SEQUENCE; SUBUNIT GENE; NEGATIVE REGULATION; MOLECULAR-CLONING; RESPONSE ELEMENT; DNA-BINDING AB Follicle-stimulating hormone (FSH), the primary stimulus for egg and sperm maturation in mammals, is an alpha/beta-heterodimer. Each subunit is encoded by a single-copy gene in the human, bovine, and rat genomes. Transcription of both subunits is inhibited by estradiol and progesterone in ovine pituitary cultures. We report the sequence of one ovine FSH-beta gene (-1,527 to +3,664) that is expressed in vivo and the identification of a novel, second ovine FSH-beta-like sequence. Digestion of ovine genomic DNA with Bgl II yielded two fragments of 10 kb and 15 kb that hybridized to a bovine FSH-beta cDNA. The 10-kb fragment contained 6 kb of 5'-flanking region and all but about 200 bp of the 3' terminus of the ovine FSH-beta gene. This FSH-beta gene encodes a protein that differs from the published ovine protein sequence only at the carboxy terminus (Arg-109Glu-110[STOP codon] instead of Glu-109Arg-110[Glx-111]) and at positions 49 (Ala instead of Thr) and 88 (Arg instead of Ser). This gene is organized similarly to the human, bovine, porcine, and rat FSH-beta genes, and its coding sequence is nearly identical (99.5%) to a reported ovine FSH-beta cDNA. Expression of the FSH-beta gene on the 10-kb fragment in vivo was determined by analysis of wether mRNA using the polymerase chain reaction. A 95-bp sequence of the 15-kb fragment was 87% homologous to the corresponding coding region of the 10-kb fragment. This comparison suggested that the 15-kb fragment contains either an FSH-beta-like sequence or a pseudogene. Several potential steroid response elements were found by sequence analysis of the 5'-flanking region of the FSH-beta gene on the 10-kb fragment. A mechanism by which these elements may act is suggested. C1 N CAROLINA STATE UNIV,DEPT BIOCHEM,NCSU BOX 7622,RALEIGH,NC 27695. NIEHS,RES TRIANGLE PK,NC 27709. DUKE UNIV,MED CTR,DIV DERMATOL,DURHAM,NC 27710. FU NICHD NIH HHS [HD-10773] NR 51 TC 27 Z9 36 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD OCT PY 1991 VL 10 IS 8 BP 593 EP 601 DI 10.1089/dna.1991.10.593 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA GL704 UT WOS:A1991GL70400005 PM 1930694 ER PT J AU COHEN, LG BANDINELLI, S SATO, S KUFTA, C HALLETT, M AF COHEN, LG BANDINELLI, S SATO, S KUFTA, C HALLETT, M TI ATTENUATION IN DETECTION OF SOMATOSENSORY STIMULI BY TRANSCRANIAL MAGNETIC STIMULATION SO ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE SOMATOSENSORY STIMULI; TRANSCRANIAL MAGNETIC STIMULATION ID CORTICAL EVOKED-POTENTIALS; VOLUNTARY MOVEMENT; BRAIN-STIMULATION; ACTIVE MOVEMENT; TRANSMISSION; SUPPRESSION; PERCEPTION; INHIBITION; MECHANISMS; CORTEX AB Effects of magnetic stimulation (MS) of the scalp and direct cortical electrical stimulation on detection of an electrical stimulus to the index finger (S1) were studied in 7 normal volunteers and a patient with epilepsy. Detection of somatosensory stimuli was attenuated when MS was delivered 200 msec before S1, was blocked when MS was delivered simultaneously to and 20 msec after S1, and was fully recovered when MS was delivered 200 msec after S1. This effect showed topographic specificity, being produced by scalp stimulation of restricted scalp positions contralateral to the finger stimulated, was maximal with low intensities of finger stimulation and high intensities of MS (usually over that required for motor threshold), and could also be produced in the absence of motor evoked responses in a peripheral hand muscle. These results show that a focal cortical stimulus can briefly attenuate detection of somatosensory stimuli before, during, and after cortical arrival of a somatosensory afferent volley. Several different mechanisms probably contribute to this phenomenon. RP COHEN, LG (reprint author), NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,HUMAN CORT PHYSIOL UNIT,BLDG 10,BETHESDA,MD 20892, USA. NR 40 TC 97 Z9 97 U1 2 U2 7 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 OCT PY 1991 VL 81 IS 5 BP 366 EP 376 DI 10.1016/0168-5597(91)90026-T PG 11 WC Engineering, Biomedical; Clinical Neurology SC Engineering; Neurosciences & Neurology GA GN064 UT WOS:A1991GN06400007 PM 1718723 ER PT J AU TIETZ, D GOMBOCZ, E CHRAMBACH, A AF TIETZ, D GOMBOCZ, E CHRAMBACH, A TI PROCEDURES AND COMPUTER-PROGRAM FOR DERIVING THE FERGUSON PLOT FROM ELECTROPHORESIS IN A SINGLE PORE GRADIENT GEL - APPLICATION TO AGAROSE-GEL AND A POLYSTYRENE PARTICLE SO ELECTROPHORESIS LA English DT Article ID SIZE STANDARDS; FREE MOBILITY; POLYACRYLAMIDE; PROTEINS; VOLTAGE AB This study presents a computerized evaluation of pore gradient gel electrophoretograms to arrive at estimates for both the particle-free mobility and retardation coefficient, which is related to particle size. Agarose pore gradient gels ranging from 0.2 to 1.1 % agarose were formed. Gel gradients were stabilized during their formation by a density gradient of 0-20% 5-(N-2,3-dihydroxypropylacetamido) 2,4,6-triiodo-N,N'bis-(2,3-dihydroxypropyl)-isophthalamide (Nycodenz). Densitometry of gelled-in Bromophenol Blue showed that these pore gradients exhibited a linear central segment and were reproducible. Migration distances of polystyrene sulfate microspheres (36.5 nm radius) in agarose pore gradient gel electrophoresis were determined by time-lapse photography at several durations of electrophoresis. These migration distances were evaluated as a function of migration time as previously reported (D. Tietz, Adv. Electrophoresis 1988, 2, 109-169). Although this is not necessarily required, the mathematical approach used in this study assumed linearity of both the pore gradient and the Ferguson plot for reasons of simplicity. The data evaluation on the basis of the extended Ogston model is incorporated in a user-friendly program, GRADFIT, which is designed for personal computers (Macintosh). The results obtained are compared with (1) conventional electrophoresis using several gels of single concentration with and without Nycodenz, and (ii) a different mathematical approach for the analysis of gradient gels (Rodbard et al., Anal. Biochem. 1971, 40, 135-157). Moreover, a simple procedure for evaluating linear pore gradient gels using linear regression analysis is presented. It is concluded that the values of particle-free mobility and retardation coefficient derived from pore gradient gel electrophoresis using the different mathematical methods are statistically indistinguishable from each other. However, these values are different, albeit close, to those obtained from conventional Ferguson plots. One of the possible reasons for this relatively minor discrepancy is that the particle-free mobility changed slightly during electrophoresis, which has a different effect on electrophoresis in homogeneous gels (single time measurement) and pore gradient gels (multiple time measurements). The characterization of particles according to size and charge by pore gradient electrophoresis provides a significant operational simplification and sample economy compared to that requiring the use of several gel concentrations, although at the price of increased requirements of instrumentation. C1 BUNDESANSTALT LEBENSMITTELUNTERSUCHUNG & FORSCH,BIOCHEM ANALYT LAB,A-1090 VIENNA,AUSTRIA. RP TIETZ, D (reprint author), NICHHD,THEORET & PHYS BIOL LAB,MACROMOLEC ANAL SECT,BLDG 10,RM 6C-101,BETHESDA,MD 20892, USA. NR 33 TC 8 Z9 8 U1 1 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 OCT PY 1991 VL 12 IS 10 BP 710 EP 721 DI 10.1002/elps.1150121005 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA GM526 UT WOS:A1991GM52600004 PM 1802689 ER PT J AU PEARCE, EJ MAGEE, AI SMITHERS, SR SIMPSON, AJG AF PEARCE, EJ MAGEE, AI SMITHERS, SR SIMPSON, AJG TI SM25, A MAJOR SCHISTOSOME TEGUMENTAL GLYCOPROTEIN, IS DEPENDENT ON PALMITIC ACID FOR MEMBRANE ATTACHMENT SO EMBO JOURNAL LA English DT Article DE ANCHOR; MEMBRANE; PALMITOYLATION; SCHISTOSOME; THIOESTER ID ROUS-SARCOMA VIRUS; TRYPANOSOMA-BRUCEI; TRANSFORMING PROTEIN; ESCHERICHIA-COLI; MYRISTIC ACID; FATTY-ACID; MANSONI; PHOSPHATIDYLINOSITOL; ANTIGENS; MICE AB Sm25, a major antigen in the surface tegument of the parasitic helminth Schistosoma mansoni, is a 25 kDa N-glycosylated glycoprotein which co-purifies with isolated surface membranes and behaves as an integral membrane protein in Triton X-114 (TX-114). The deduced amino acid sequence of Sm25 shows a short C-terminal hydrophobic domain between residues 163 and 180, containing six uncharged polar amino acids and followed by a Lysl8l-Serl92 dipeptide. We were interested in whether or not this marginal C-terminal amphiphilic domain is responsible for the association of Sm25 with the membrane or whether a post-translational modification such as the addition of glycosyl phosphatidyl inositol (GPI) represents the membrane anchor for this molecule. We rind that treatment with phosphatidyl inositol-specific phospholipase C, which cleaves many GPI anchors, does not reveal Cross Reacting Determinant (CRD) on Sm25, nor affect the association of this protein with membranes, providing no support for the addition of GPI. However, Sm25 is palmitoylated via a thioester bond to the single Cys residue, at position 168, which lies within the C-terminal hydrophobic domain. Removal of palmitate by reduction results in a marked decrease in the hydrophobicity of Sm25, as demonstrated by its partitioning into the aqueous rather than detergent phase of TX-114 and its quantitative release from membrane preparations. The hydrophobicity of several membrane proteins in addition to Sm25 is also decreased by reduction, raising the possibility that fatty acylation by, thioester linkage is an important mechanism used by schistosomes to stabilize protein - membrane interactions. C1 NIAID,PARASIT DIS SECT,IMMUNOL & CELL BIOL SECT,BETHESDA,MD 20892. NATL INST MED RES,EUKARYOT MOLEC GENET LAB,LONDON NW7 1AA,ENGLAND. NATL INST MED RES,DIV PARASITOL,LONDON NW7 1AA,ENGLAND. NR 33 TC 23 Z9 24 U1 0 U2 5 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 OCT PY 1991 VL 10 IS 10 BP 2741 EP 2746 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GF615 UT WOS:A1991GF61500004 PM 1833182 ER PT J AU BONIFACINO, JS COSSON, P SHAH, N KLAUSNER, RD AF BONIFACINO, JS COSSON, P SHAH, N KLAUSNER, RD TI ROLE OF POTENTIALLY CHARGED TRANSMEMBRANE RESIDUES IN TARGETING PROTEINS FOR RETENTION AND DEGRADATION WITHIN THE ENDOPLASMIC-RETICULUM SO EMBO JOURNAL LA English DT Article DE DEGRADATION SIGNALS; MEMBRANE PROTEINS; MEMBRANE TRANSPORT; PROTEIN TURNOVER ID CELL ANTIGEN RECEPTOR; HUMAN INTERLEUKIN-2 RECEPTOR; STEROL-ENHANCED DEGRADATION; AMINO-ACID SUBSTITUTIONS; PRE-GOLGI DEGRADATION; MEMBRANE-BOUND DOMAIN; COENZYME-A REDUCTASE; INTRACELLULAR-TRANSPORT; SURFACE EXPRESSION; APOLIPOPROTEIN-B AB The selective breakdown of newly synthesized proteins retained within the endoplasmic reticulum (ER) is probably mediated by the specific recognition of structural features of protein substrates by components of a degradative system. Within the ce chain of the multisubunit T-cell antigen receptor (TCR) complex, a transmembrane sequence containing two basic amino acid residues has been shown to act as a determinant for retention and rapid degradation in the ER. We now demonstrate that single basic or acidic amino acid residues can cause targeting for retention and degradation in the ER when placed within the transmembrane domain of an integral membrane protein normally destined for the cell surface. The effect of such potentially charged residues is dependent on their relative position within the transmembrane sequence and on the nature of the amino acid side chains. The phenotypic changes induced by potentially charged transmembrane residues occur without apparent alterations of the global folding or transmembrane topology of the mutant proteins. These observations test the hypothesis that potentially charged residues within transmembrane domains can provide the basis for a motif for ER degradation and explain the selective breakdown of some proteins retained within the ER. RP BONIFACINO, JS (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 62 TC 159 Z9 159 U1 1 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 OCT PY 1991 VL 10 IS 10 BP 2783 EP 2793 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GF615 UT WOS:A1991GF61500009 PM 1915263 ER PT J AU MCMAHAN, CJ SLACK, JL MOSLEY, B COSMAN, D LUPTON, SD BRUNTON, LL GRUBIN, CE WIGNALL, JM JENKINS, NA BRANNAN, CI COPELAND, NG HUEBNER, K CROCE, CM CANNIZZARRO, LA BENJAMIN, D DOWER, SK SPRIGGS, MK SIMS, JE AF MCMAHAN, CJ SLACK, JL MOSLEY, B COSMAN, D LUPTON, SD BRUNTON, LL GRUBIN, CE WIGNALL, JM JENKINS, NA BRANNAN, CI COPELAND, NG HUEBNER, K CROCE, CM CANNIZZARRO, LA BENJAMIN, D DOWER, SK SPRIGGS, MK SIMS, JE TI A NOVEL IL-1 RECEPTOR, CLONED FROM B-CELLS BY MAMMALIAN EXPRESSION, IS EXPRESSED IN MANY CELL-TYPES SO EMBO JOURNAL LA English DT Article DE B-CELL; CHROMOSOME MAPPING; EXPRESSION CLONING; INTERLEUKIN-1; RECEPTOR ID EPSTEIN-BARR-VIRUS; HUMAN INTERLEUKIN-1 RECEPTOR; FIBROBLAST GROWTH-FACTORS; HIGH-AFFINITY RECEPTORS; VACCINIA VIRUS; ESCHERICHIA-COLI; T-CELLS; IMMUNOGLOBULIN SUPERFAMILY; MOLECULAR-PROPERTIES; NUCLEOTIDE-SEQUENCE AB cDNA clones corresponding to an M(r) approximately 80 000 receptor (type I receptor) for interleukin-1 (IL-1) have been isolated previously by mammalian expression. Here, we report the use of an improved expression cloning method to isolate human and murine cDNA clones encoding a second type (M(r) approximately 60 000) of IL-1 receptor (type II receptor). The mature type II IL-1 receptor consists of (i) a ligand binding portion comprised of three immunoglobulin-like domains; (ii) a single transmembrane region; and (iii) a short cytoplasmic domain of 29 amino acids. This last contrasts with the approximately 215 amino acid cytoplasmic domain of the type I receptor, and suggests that the two IL-1 receptors may interact with different signal transduction pathways. The type II receptor is expressed in a number of different tissues, including both B and T lymphocytes, and can be induced in several cell types by treatment with phorbol ester. Both IL-1 receptors appear to be well conserved in evolution, and map to the same chromosomal location. Like the type I receptor, the human type II IL-1 receptor can bind all three forms of IL-1 (IL-1-alpha, IL-1-beta and IL-1ra). Vaccinia virus contains an open reading frame bearing strong resemblance to the type II IL-1 receptor. C1 IMMUNEX RES & DEV CORP,DEPT BIOCHEM,SEATTLE,WA 98101. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. TEMPLE UNIV,HLTH SCI CTR,SCH MED,FELS INST CANC RES & MOLEC BIOL,PHILADELPHIA,PA 19140. OHIO STATE UNIV HOSP,ARTHUR G JAMES CANC INST,DIV HEMATOL & ONCOL,COLUMBUS,OH 43210. RP MCMAHAN, CJ (reprint author), IMMUNEX RES & DEV CORP,DEPT MOLEC BIOL,51 UNIV ST,SEATTLE,WA 98101, USA. FU NCI NIH HHS [N01-CO-74101]; NIAID NIH HHS [AI31262] NR 83 TC 625 Z9 632 U1 0 U2 13 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 OCT PY 1991 VL 10 IS 10 BP 2821 EP 2832 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GF615 UT WOS:A1991GF61500013 PM 1833184 ER PT J AU ARCANGIOLI, B KLAR, AJS AF ARCANGIOLI, B KLAR, AJS TI A NOVEL SWITCH-ACTIVATING SITE (SAS1) AND ITS COGNATE BINDING-FACTOR (SAP1) REQUIRED FOR EFFICIENT MAT1 SWITCHING IN SCHIZOSACCHAROMYCES-POMBE SO EMBO JOURNAL LA English DT Article DE DOUBLE-STRANDED BREAK; FISSION YEAST; MATING TYPE SWITCHING; STEM CELL LINEAGE; SWITCH-ACTIVATING PROTEIN; SWITCH-ACTIVATING SITE ID MATING-TYPE CASSETTES; FISSION YEAST; GEL-ELECTROPHORESIS; SACCHAROMYCES-CEREVISIAE; GENES; TRANSPOSITION; BREAKS; CELLS; TRANSFORMATION; EXPRESSION AB The pattern of parental DNA strand inheritance at the mating type locus (mat1) determines the pattern of mat1 switching in a cell lineage by regulating the formation of the site-specific double-stranded break (DSB) required for mating type interconversion in Schizosaccharomyces pombe. To study the molecular basis of this programmable cell type change, we conducted structural and functional analyses of the DNA sequence flanking the DSB at mat1. We have identified and characterized a DNA-binding activity that interacts with a specific sequence located 140 bp from the DSB site. Deletion analysis of DNA sequences located distal to mat1 cassette revealed the presence of at least two switch-activating sites (SASI and SAS2), both of which are required for generating an efficient level of DSBs and consequently, for efficient switching. We found that SASI overlaps with the target site of the DNA-binding activity called SAP1 (for switch-activating protein). Point mutations generated in the SASI element that adversely affect binding to SAP1 protein in vitro were found to reduce the efficiency of switching in vivo, suggesting the requirement of SAP1 for switching. Pedigree analysis revealed that SAS1 is equally required for initial switching (one switch in four granddaughters of a cell) and for consecutive switching (where the sister of a recently switched cell switches again), indicating that the two developmentally asymmetric cell divisions required to generate a particular pattern of switching share the same molecular control mechanism. RP ARCANGIOLI, B (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21701, USA. FU NCI NIH HHS [N01-CO-74101] NR 38 TC 73 Z9 74 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD OCT PY 1991 VL 10 IS 10 BP 3025 EP 3032 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GF615 UT WOS:A1991GF61500035 PM 1915277 ER PT J AU SHIMIZU, M ROTH, SY SZENTGYORGYI, C SIMPSON, RT AF SHIMIZU, M ROTH, SY SZENTGYORGYI, C SIMPSON, RT TI NUCLEOSOMES ARE POSITIONED WITH BASE PAIR PRECISION ADJACENT TO THE ALPHA-2 OPERATOR IN SACCHAROMYCES-CEREVISIAE SO EMBO JOURNAL LA English DT Article DE CHROMATIN; NUCLEOSOME POSITIONING; REPRESSION; YEAST MATING TYPE ID PROTEIN-DNA INTERACTIONS; MATING-TYPE LOCUS; CELL-TYPE; GENE ENCODES; YEAST; REPRESSOR; CHROMATIN; UPSTREAM; INVIVO; PROMOTER AB Analysis of the chromatin structure of minichromosomes containing the binding site for the yeast alpha-2 repressor protein by indirect end-labeling has previously indicated that nucleosomes are stably positioned over sequences adjacent to the alpha-2 operator in the presence of the repressor. Development of a primer extension assay for nucleosome position now allows a more detailed examination of the location of these nucleosomes relative to the operator sequence, and indicates that nucleosomes are precisely and stably positioned both translationally and rotationally over sequences adjoining the operator. In addition, this assay enables analysis of the chromatin structure of single copy, genomic sequences. Chromatin structures determined for two genes regulated by alpha-2, STE6 and BAR1, are consistent with nucleosomes precisely positioned downstream of the operator sequence, incorporating promoter elements, in alpha-cells but not in a-cells. The location of these nucleosomes relative to the operator sequence is highly analogous to that observed in the minichromosome. The stability of the nucleosomes adjacent to the operator together with the precision of their location suggests that they may play a role in repression of a-specific gene expression by alpha-2. Further, the primer extension assay allow a comparison of the structure of these positioned nucleosomes formed in vivo to that previously described for core particles reconstituted in vitro. C1 NIDDKD,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892. NR 48 TC 153 Z9 155 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 OCT PY 1991 VL 10 IS 10 BP 3033 EP 3041 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA GF615 UT WOS:A1991GF61500036 PM 1915278 ER PT J AU MEZEY, E KISS, JZ AF MEZEY, E KISS, JZ TI COEXPRESSION OF VASOPRESSIN AND OXYTOCIN IN HYPOTHALAMIC SUPRAOPTIC NEURONS OF LACTATING RATS SO ENDOCRINOLOGY LA English DT Article ID HYBRIDIZATION HISTOCHEMISTRY; NEUROHYPOPHYSEAL SYSTEM; INSITU HYBRIDIZATION; MESSENGER-RNA; IMMUNOCYTOCHEMICAL LOCALIZATION; ARGININE VASOPRESSIN; BRATTLEBORO RATS; MENSTRUAL-CYCLE; NEUROPHYSIN; PRECURSOR AB Magnocellular hypothalamic neurons in the rat supraoptic nucleus (SON) normally produce either vasopressin (VP) or oxytocin (OT). Here we demonstrate that many magnocellular neurons in the SON of lactating rats synthesize both hormones at the same time. We show the colocalization of the messenger (m) RNA that encodes the VP precursor with OT-neurophysin; OT mRNA with VP-neurophysin, the C-terminal glycopeptide of the VP precursor, and VP itself, and the presence of both mRNAs in the same cell. At the light microscopic level quantitative studies show that on the second day of lactation, 17% of the SON neurons produce both hormones, on the fifth day 13%, and on the ninth day 9%. Two days after lactation the number of cells that are positive for both hormones returns to the control level (2-3%). We also show by means of electron microscopic immunohistochemistry that both peptides (or their precursors) are present in the same neurosecretory vesicles in nerve endings in the posterior lobe of lactating rats. At the electron microscopic level quantitative studies show that on the second day of lactation 21% of the terminals contain mixed vesicles; this number increases to 24% by the fourth day and is down to 5% by the 15th day, a level similar to that found in control rats. Since the double-labeled cells seemed to be producing additional VP as opposed to OT, we hypothesized that the former should affect urinary osmolality. Urine samples of lactating rats show a significant (5-fold) increase in urine osmolality during lactation (highest on the second day). The increase in osmolality correlated with the increase in the number of VP positive cells during lactation. We suggest that magnocellular neurons that ordinarily synthesize little or no VP can produce this antidiuretic hormone to help the animal compensate for the loss of water associated with lactation. C1 SEMMELWEIS UNIV MED,SCH MED,DEPT ANAT 1,H-1085 BUDAPEST 8,HUNGARY. UNIV GENEVA,DEPT ANAT,CH-1211 GENEVA 4,SWITZERLAND. RP MEZEY, E (reprint author), NIMH,CELL BIOL LAB,BLDG 36,ROOM 3A17,BETHESDA,MD 20892, USA. NR 36 TC 102 Z9 103 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 OCT PY 1991 VL 129 IS 4 BP 1814 EP 1820 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GH336 UT WOS:A1991GH33600022 PM 1915070 ER PT J AU MERCHENTHALER, I LOPEZ, FJ LENNARD, DE NEGROVILAR, A AF MERCHENTHALER, I LOPEZ, FJ LENNARD, DE NEGROVILAR, A TI SEXUAL DIFFERENCES IN THE DISTRIBUTION OF NEURONS COEXPRESSING GALANIN AND LUTEINIZING-HORMONE-RELEASING HORMONE IN THE RAT-BRAIN SO ENDOCRINOLOGY LA English DT Article ID GROWTH-HORMONE; ANTERIOR-PITUITARY; PREOPTIC AREA; SECRETION; ESTROGEN; IMMUNOREACTIVITY; INVITRO; LH; INVOLVEMENT; COEXISTENCE AB We have recently reported that a subpopulation of galanin (GAL)-immunoreactive perikarya in the preoptic area near the organum vasculosum of the lamina terminalis (OVLT) has morphological characteristics similar to those of LHRH-containing neurons. In fact, both peptides are colocalized in those neurons in the male rat brain. In these studies we describe sexual differences in the incidence of neurons colocalizing GAL and LHRH in this region. In male rats, about 20% of LHRH-immunoreactive cells in the diagonal band of Broca and the medial preoptic area are also immunoreactive for GAL. In contrast, in female rats, about 65% of LHRH-containing perikarya near the OVLT are immunostained for GAL. In addition, GAL and LHRH levels were measured in tissue extracts containing either the OVLT and surrounding areas or the median eminence. The data indicate that the preoptic area, including the OVLT, contains a significantly higher amount of GAL in females killed in proestrus than in those killed in estrus. The amount of GAL measured in males is lower than that in the proestrous females, but somewhat greater than that present in the estrous females. There were no significant differences among the three groups in LHRH content in this region. The GAL content of the median eminence was the highest in proestrous females, followed by estrous females and males. The LHRH content in the median eminence was not significantly different among the three groups. In conclusion, these observations indicate that the coexpression of GAL with LHRH in a discrete subpopulation of LHRH-producing neurons is a sex-related phenomenon. The fact that changes in GAL levels in specific regions can be seen at different times during the estrous cycle suggests that gonadal steroids, possibly estrogens, may physiologically regulate the expression of GAL in this subpopulation of LHRH neurons. C1 NIEHS, MOLEC & INTEGRAT NEUROSCI LAB, REPROD NEUROENDOCRINOL SECT, RES TRIANGLE PK, NC 27709 USA. RP NIEHS, MOLEC & INTEGRAT NEUROSCI LAB, FUNCT MORPHOL SECT, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 57 TC 104 Z9 105 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1991 VL 129 IS 4 BP 1977 EP 1986 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GH336 UT WOS:A1991GH33600041 PM 1717240 ER PT J AU GIBSON, MK NEMMERS, LA BECKMAN, WC DAVIS, VL CURTIS, SW KORACH, KS AF GIBSON, MK NEMMERS, LA BECKMAN, WC DAVIS, VL CURTIS, SW KORACH, KS TI THE MECHANISM OF ICI-164,384 ANTIESTROGENICITY INVOLVES RAPID LOSS OF ESTROGEN-RECEPTOR IN UTERINE TISSUE SO ENDOCRINOLOGY LA English DT Article ID BREAST-CANCER; GLUCOCORTICOID RECEPTOR; DNA-BINDING; PURE ANTIESTROGEN; MOUSE UTERUS; RAT UTERUS; TAMOXIFEN; DOMAINS; ACTIVATION; LIGAND AB The antiestrogen ICI 164,384 (ICI) binds the estrogen receptor (ER) with approximately 20% the affinity of estradiol, but without the partial agonistic effects caused by tamoxifen. Investigations into the mechanism of ICI action have used ER molecules expressed in vitro to examine the binding of ER to ICI and the capacity of ICI-ER complexes to dimerize and bind to the estrogen response element (ERE). Our objectives were to study the biological effects, cellular distribution, and ERE-binding capacity of native uterine ICI-ER complexes after ip injection of 1 mg/kg ICI into 10-day castrate adult female mice. Synthesis of DNA and progesterone receptor were measured as end points of agonistic activity. ICI failed to stimulate either DNA or progesterone receptor synthesis above control levels, and pretreatment with ICI for 0.5 h reduced the stimulatory effect of estradiol by 75%. Measurement of uterine nuclear ER and cytosolic levels by exchange binding assay indicated a reduction in total ER levels within 0.5 h after ICI treatment, which remained below 20% for 24 h. Cycloheximide treatment did not block the ICI effect. Western blot analysis, immunohistochemistry, and steroid autoradiography confirmed the loss of ER protein. The ICI effect on ER was also demonstrable in vitro in the mouse TM4 estrogen-responsive cell line. ICI dramatically reduced ER levels to 5% of the control value by 4 h. Northern analysis indicated that ICI did not affect ER message levels, suggesting that the observed reduction in ER did not occur at the level of transcription. Gel shift assays indicated a low, but detectable, amount of ICI-ER binding to the vitellogenin A2 (VitA2) ERE. These results suggest that, although the ICI-ER complex binds weakly to DNA, ICI may cause its antagonistic effect by producing a rapid disappearance of the ER from the target tissue, resulting in an insufficient amount of ER to bind the native ligand and elicit agonist responses. C1 NIEHS,RECEPTOR BIOL SECT,REPROD & DEV TOXICOL LAB,POB 12233,RES TRIANGLE PK,NC 27709. OI Korach, Kenneth/0000-0002-7765-418X NR 50 TC 184 Z9 186 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 OCT PY 1991 VL 129 IS 4 BP 2000 EP 2010 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GH336 UT WOS:A1991GH33600043 PM 1915080 ER PT J AU BLITHE, DL RICHARDS, RG SKARULIS, MC AF BLITHE, DL RICHARDS, RG SKARULIS, MC TI FREE ALPHA MOLECULES FROM PREGNANCY STIMULATE SECRETION OF PROLACTIN FROM HUMAN DECIDUAL CELLS - A NOVEL FUNCTION FOR FREE ALPHA IN PREGNANCY SO ENDOCRINOLOGY LA English DT Note ID HUMAN CHORIONIC-GONADOTROPIN; GLYCOPROTEIN HORMONES; AMNIOTIC-FLUID; LACTOTROPE DIFFERENTIATION; CLEARANCE RATES; SUBUNIT; SERUM; PITUITARY; INVITRO; TISSUE AB Free alpha molecules isolated from pregnancy, as well as highly purified reference preparations of hCG-alpha subunit (CR119 or CR123), stimulated the release of prolactin from human decidual cells in culture. The amount of prolactin secreted during a 24 h incubation was concentration-dependent over a range of increasing doses of alpha from 0.2 to 20 ng/ml with an ED50 of about 1.6 ng/ml. These concentrations are well within the physiologic maternal serum free alpha levels which average 350 ng/ml during the third trimester of pregnancy. Incubation of decidual cells with a reference preparation of intact hCG (CR123) at a concentration of 260 ng/ml resulted in stimulated secretion of prolactin, however, the observed stimulation could be attributed to contamination of the preparation with free alpha or dissociated hCG-alpha subunit. Purified hCG-beta subunit had no stimulatory activity on the decidual cell culture. The effect of alpha subunit on the stimulated release of prolactin was not due to a generalized stimulation of protein synthesis and secretion since no increase was observed in the release of S-35-labeled proteins compared to controls. In addition, the observed increase in prolactin secretion was not due to a toxic effect of the alpha subunit since there was no visible effect on cell viability, and the cellular enzymes, LDH and alkaline phosphatase, were not detected in the culture medium. Addition of exogenous hCG-alpha subunit to primary cultures of human trophoblast cultures did not result in stimulated release of human placental lactogen. We conclude that free alpha molecules of pregnancy stimulate release of prolactin from human decidual cells in culture. These results suggest a novel role for free alpha in the paracrine regulation of decidual prolactin secretion. C1 CHILDRENS HOSP MED CTR,CINCINNATI,OH 45229. UNIV CINCINNATI,COLL MED,CINCINNATI,OH 45229. RP BLITHE, DL (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N262,BETHESDA,MD 20892, USA. FU NICHD NIH HHS [HD-15201-12] NR 27 TC 76 Z9 77 U1 0 U2 3 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1991 VL 129 IS 4 BP 2257 EP 2259 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GH336 UT WOS:A1991GH33600080 PM 1717245 ER PT J AU CULLER, MD PASCHALL, CS AF CULLER, MD PASCHALL, CS TI PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE (PACAP) POTENTIATES THE GONADOTROPIN-RELEASING ACTIVITY OF LUTEINIZING-HORMONE-RELEASING HORMONE SO ENDOCRINOLOGY LA English DT Note ID HYPOTHALAMIC PEPTIDE AB In order to determine if the newly discovered neuropeptide, pituitary adenylate cyclase activating polypeptide (PACAP), interacts with the known hypothalamic releasing factors to modulate pituitary hormone secretion, the effect of PACAP, either alone or in combination with either LHRH, TRH, CRF or GHRH, was examined in rat anterior pituitary cell cultures. While PACAP alone weakly stimulated LH and FSH release, PACAP and LHRH, in combination, interacted synergistically to stimulate gonadotropin secretion. No significant changes in the secretion of either TSH, ACTH, or GH were observed in response to PACAP, either alone or in combination with the other releasing factors. Addition of an LHRH antagonist demonstrated that the PACAP effect on gonadotropin release was neither mediated by the LHRH receptor nor the result of LHRH contamination of the PACAP preparation. Because of the sequence homology (68%) between the N-terminal 28 amino acids of PACAP and VIP, the addition of a VIP antagonist was used to demonstrate that the PACAP effect is not mediated through the VIP receptor. The observation that PACAP interacts synergistically with LHRH in stimulating gonadotropin release suggests intriguing possibilities for PACAP in regulating gonadotropin secretion and reproductive function. RP CULLER, MD (reprint author), NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,REPROD NEUROENDOCRINOL SECT,RES TRIANGLE PK,NC 27709, USA. NR 8 TC 173 Z9 175 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 OCT PY 1991 VL 129 IS 4 BP 2260 EP 2262 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GH336 UT WOS:A1991GH33600081 PM 1915106 ER PT J AU OSORNIOVARGAS, AR HERNANDEZRODRIGUEZ, NA YANEZBURUEL, AG USSLER, W OVERBY, LH BRODY, AR AF OSORNIOVARGAS, AR HERNANDEZRODRIGUEZ, NA YANEZBURUEL, AG USSLER, W OVERBY, LH BRODY, AR TI LUNG-CELL TOXICITY EXPERIMENTALLY INDUCED BY A MIXED DUST FROM MEXICALI, BAJA-CALIFORNIA, MEXICO SO ENVIRONMENTAL RESEARCH LA English DT Article ID DEPOSITION PATTERN; SILICATE PNEUMOCONIOSIS; PULMONARY MACROPHAGES; CHRYSOTILE ASBESTOS; ALVEOLAR LEVEL; ST-HELENS; INHALATION; RATS; GENERATION; ACTIVATION C1 NIEHS,PULM PATHOBIOL LAB,RES TRIANGLE PK,NC 27709. NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,CURRICULUM TOXICOL,CHAPEL HILL,NC 27599. RP OSORNIOVARGAS, AR (reprint author), INST NACL CARDIOL IGNACIO CHAVEZ,DEPT BIOCHEM,DIV INVEST BASICA,AVE SAN FERNANDO 22,MEXICO CITY 14000,DF,MEXICO. RI Osornio Vargas, Alvaro/D-4012-2009; Osornio Vargas, Alvaro/B-4645-2010 OI Osornio Vargas, Alvaro/0000-0001-8287-7102 NR 27 TC 17 Z9 17 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD OCT PY 1991 VL 56 IS 1 BP 31 EP 47 DI 10.1016/S0013-9351(05)80107-0 PG 17 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA GJ992 UT WOS:A1991GJ99200004 PM 1655401 ER PT J AU DEVI, SJN MURRAY, CJ AF DEVI, SJN MURRAY, CJ TI COCKROACHES (BLATTA AND PERIPLANETA SPECIES) AS RESERVOIRS OF DRUG-RESISTANT SALMONELLAS SO EPIDEMIOLOGY AND INFECTION LA English DT Article AB A total of 221 cockroaches (Blatta and Periplaneta spp.), collected in hospitals, houses, animal sheds, grocery stores and restaurants, in various parts of South Kanara District, a south-west coastal region of India, were studied bacteriologically for the presence of various salmonellas. Salmonellas were isolated from 4.1% of these cockroaches. Nine strains of salmonellas were recovered. belonging to five serotypes - Salmonella bovismorbificans, S. oslo, S. typhimurium, S. mbandaka and S. braenderup, the former two being the commonest serotypes. All salmonellas were resistant to one or other of 11 antibacterial drugs used in the susceptibility test. Isolation of salmonellas from cockroaches collected from the livestock premises and human dwellings suggested that they may act as significant reservoirs of salmonella in nature. Recovery of serotypes, phage types and R-types that were commonly isolated from humans and animals of this locality, suggested a transmission role for cockroaches. By harbouring potentially pathogenic, drug-resistant salmonellas. these wandering arthropods may pose dangerous infective hazards to humans and animals. C1 INST MED & VET SCI,SALMONELLA REFERENCE LAB,ADELAIDE,SA 5000,AUSTRALIA. RP DEVI, SJN (reprint author), NICHHD,DEV & MOLEC IMMUN LAB,BLDG 6,ROOM 1A05,BETHESDA,MD 20892, USA. NR 26 TC 18 Z9 19 U1 3 U2 6 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0950-2688 J9 EPIDEMIOL INFECT JI Epidemiol. Infect. PD OCT PY 1991 VL 107 IS 2 BP 357 EP 361 PG 5 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA GN842 UT WOS:A1991GN84200011 PM 1936157 ER PT J AU BIRCH, NP BENNETT, HPJ ESTIVARIZ, FE LOH, YP AF BIRCH, NP BENNETT, HPJ ESTIVARIZ, FE LOH, YP TI EFFECT OF CALCIUM-IONS ON THE PROCESSING OF PROOPIOMELANOCORTIN BY BOVINE INTERMEDIATE LOBE PRO-OPIOMELANOCORTIN-CONVERTING ENZYME SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article ID SECRETORY VESICLES; PURIFICATION; GRANULES; PROTEOLYSIS; PRECURSORS; EXCHANGE; CA-2+; PH AB The effect of Ca2+ on the extent and pattern of processing of pro-opiomelanocortin and an N-terminal fragment by a purified pituitary secretory vesicle, soluble aspartic endoprotease, was studied. Ca2+ stimulated the first cleavage of pro-opiomelanocortin by pro-opiomelanocortin-converting enzyme to yield 21 - 23 kDa adrenocorticotropin and beta-lipotropin, but its effect was minimal. The production of adrenocorticotropin from the 21 - 23 kDa intermediate was stimulated approximately 2.3-fold in the presence of 10 mM Ca2+, and processing of beta-lipotropin to beta-endorphin was stimulated about 1.3 - 1.4-fold by 5-10 mM Ca2+. The production of gamma-melanotropin-immunoreactive material from bovine N-pro-opiomelanocortin(1 - 77) was stimulated approximately 1.3-fold at both 100-mu-M and 1.5-2.0 mM Ca2+. Further characterization of the gamma-melanotropin-immunoreactive material by HPLC demonstrated that the major products were gamma-3-[Lys]melanotropin and gamma-3-melanotropin at both Ca2+ concentrations. These results indicate that pro-opiomelanocortin-converting enzyme is stimulated by Ca2+. C1 NICHHD,DEV NEUROBIOL LAB,CELLULAR NEUROBIOL SECT,BLDG 36,ROOM 2A-21,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. ROYAL VICTORIA HOSP,MONTREAL H3A 1A1,QUEBEC,CANADA. RI Birch, Nigel/H-2498-2011 OI Birch, Nigel/0000-0002-8417-3587 NR 24 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD OCT 1 PY 1991 VL 201 IS 1 BP 85 EP 89 DI 10.1111/j.1432-1033.1991.tb16259.x PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GG925 UT WOS:A1991GG92500008 PM 1655430 ER PT J AU WEAVER, JL PINE, PS ASZALOS, A SCHOENLEIN, PV CURRIER, SJ PADMANABHAN, R GOTTESMAN, MM AF WEAVER, JL PINE, PS ASZALOS, A SCHOENLEIN, PV CURRIER, SJ PADMANABHAN, R GOTTESMAN, MM TI LASER SCANNING AND CONFOCAL MICROSCOPY OF DAUNORUBICIN, DOXORUBICIN, AND RHODAMINE-123 IN MULTIDRUG-RESISTANT CELLS SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID P-GLYCOPROTEIN GENE; ALTERED PATTERN; TUMOR-CELLS; TRANSPORTER; VINBLASTINE; COLCHICINE; EXPRESSION; CDNA C1 US FDA,CDER,DIV RES & TESTING,HFD-471,200 C ST SW,WASHINGTON,DC 20204. NCI,CELL BIOL LAB,BETHESDA,MD 20892. NR 17 TC 88 Z9 94 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD OCT PY 1991 VL 196 IS 2 BP 323 EP 329 DI 10.1016/0014-4827(91)90267-X PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA GG146 UT WOS:A1991GG14600024 PM 1680064 ER PT J AU WETZEL, MG LI, J ALVAREZ, RA ANDERSON, RE OBRIEN, PJ AF WETZEL, MG LI, J ALVAREZ, RA ANDERSON, RE OBRIEN, PJ TI METABOLISM OF LINOLENIC ACID AND DOCOSAHEXAENOIC ACID IN RAT RETINAS AND ROD OUTER SEGMENTS SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE DOCOSAHEXAENOIC ACID; FATTY ACIDS; LINOLENIC ACID; PHOSPHOLIPID; RATS; RETINA; ROD OUTER SEGMENTS; PHOTORECEPTOR ID UNSATURATED FATTY-ACIDS; RETINOBLASTOMA CELLS; PHOSPHATIDIC-ACID; RHESUS-MONKEYS; PHOSPHOLIPIDS; BRAIN; MEMBRANES; DEFICIENCY; GLYCEROL; INVIVO C1 NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. BAYLOR COLL MED,CULLEN EYE INST,DEPT OPHTHALMOL,HOUSTON,TX 77030. FU NEI NIH HHS [EY-00871, EY-04149] NR 32 TC 38 Z9 39 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD OCT PY 1991 VL 53 IS 4 BP 437 EP 446 DI 10.1016/0014-4835(91)90161-7 PG 10 WC Ophthalmology SC Ophthalmology GA GK210 UT WOS:A1991GK21000004 PM 1834476 ER PT J AU SMITH, SB STJULES, RS OBRIEN, PJ AF SMITH, SB STJULES, RS OBRIEN, PJ TI TRANSIENT HYPERGLYCOSYLATION OF RHODOPSIN WITH GALACTOSE SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE RHODOPSIN; RAT; RETINA; GLYCOSYLATION; GALACTOSE; LECTIN AFFINITY CHROMATOGRAPHY; RCA; RICIN ID LECTIN BINDING-SITES; PHOTORECEPTOR CELLS; BOVINE RHODOPSIN; OUTER SEGMENTS; ULTRASTRUCTURAL-LOCALIZATION; LINKED OLIGOSACCHARIDES; MEMBRANE MORPHOGENESIS; RETINAL PHOTORECEPTORS; PIGMENT-EPITHELIUM; RAT RHODOPSIN RP SMITH, SB (reprint author), NEI,RETINAL CELL & MOLEC BIOL LAB,BLDG 6,ROOM B1A04,BETHESDA,MD 20892, USA. NR 38 TC 24 Z9 24 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD OCT PY 1991 VL 53 IS 4 BP 525 EP 537 DI 10.1016/0014-4835(91)90170-J PG 13 WC Ophthalmology SC Ophthalmology GA GK210 UT WOS:A1991GK21000013 PM 1936188 ER PT J AU KNIGHT, M BRINDLEY, PJ RICHARDS, CS LEWIS, FA AF KNIGHT, M BRINDLEY, PJ RICHARDS, CS LEWIS, FA TI SCHISTOSOMA-MANSONI - USE OF A CLONED RIBOSOMAL-RNA GENE PROBE TO DETECT RESTRICTION-FRAGMENT-LENGTH-POLYMORPHISMS IN THE INTERMEDIATE HOST BIOMPHALARIA-GLABRATA SO EXPERIMENTAL PARASITOLOGY LA English DT Article ID DNA MARKERS; DIFFERENTIATION; IDENTIFICATION; SUSCEPTIBILITY; INFECTION; STRAINS C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. RP KNIGHT, M (reprint author), BIOMED RES INST,12111 PARKLAWN DR,ROCKVILLE,MD 20852, USA. FU NIAID NIH HHS [AI 2777] NR 27 TC 38 Z9 38 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD OCT PY 1991 VL 73 IS 3 BP 285 EP 294 DI 10.1016/0014-4894(91)90100-B PG 10 WC Parasitology SC Parasitology GA GK786 UT WOS:A1991GK78600006 PM 1680745 ER PT J AU DOYLE, PS ENGEL, JC PIMENTA, PFP DASILVA, PP DWYER, DM AF DOYLE, PS ENGEL, JC PIMENTA, PFP DASILVA, PP DWYER, DM TI LEISHMANIA-DONOVANI - LONG-TERM CULTURE OF AXENIC AMASTIGOTES AT 37-DEGREES-C SO EXPERIMENTAL PARASITOLOGY LA English DT Article ID TRYPANOSOMA-CRUZI; HEAT-SHOCK; BRAZILIENSIS-PANAMENSIS; ACID-PHOSPHATASE; FRACTURE-FLIP; CELL-SURFACE; PROMASTIGOTES; MEXICANA; FORMS; STAGE C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. NCI,MATH BIOL LAB,FREDERICK,MD 21701. NR 28 TC 103 Z9 104 U1 0 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD OCT PY 1991 VL 73 IS 3 BP 326 EP 334 DI 10.1016/0014-4894(91)90104-5 PG 9 WC Parasitology SC Parasitology GA GK786 UT WOS:A1991GK78600010 PM 1915747 ER PT J AU MCCARTHYBURKE, C BATES, PA DWYER, DM AF MCCARTHYBURKE, C BATES, PA DWYER, DM TI LEISHMANIA-DONOVANI - USE OF 2 DIFFERENT, COMMERCIALLY AVAILABLE, CHEMICALLY DEFINED MEDIA FOR THE CONTINUOUS INVITRO CULTIVATION OF PROMASTIGOTES SO EXPERIMENTAL PARASITOLOGY LA English DT Note C1 NIAID,PARASIT DIS LAB,CELL BIOL & IMMUNOL SECT,BETHESDA,MD 20892. UNIV GLASGOW,DEPT ZOOL,GLASGOW G12 8QQ,SCOTLAND. NR 10 TC 37 Z9 38 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD OCT PY 1991 VL 73 IS 3 BP 385 EP 387 DI 10.1016/0014-4894(91)90112-A PG 3 WC Parasitology SC Parasitology GA GK786 UT WOS:A1991GK78600018 PM 1915754 ER PT J AU KETTERLINUS, RD LAMB, ME NITZ, K AF KETTERLINUS, RD LAMB, ME NITZ, K TI DEVELOPMENTAL AND ECOLOGICAL SOURCES OF STRESS AMONG ADOLESCENT PARENTS SO FAMILY RELATIONS LA English DT Review DE ADOLESCENT PARENTS; INTERVENTIONS; PUBLIC POLICY; REVIEW; STRESS ID INFANT-MOTHER ATTACHMENT; FULL-TERM INFANTS; SOCIAL-INTERACTION; TEENAGE MOTHERS; LIFE EVENTS; INDIVIDUAL-DIFFERENCES; SOCIOECONOMIC-STATUS; SUPPORT; CHILDREN; FATHERS C1 GEORGE WASHINGTON UNIV,DEPT PSYCHOL,WASHINGTON,DC 20052. RP KETTERLINUS, RD (reprint author), NICHHD,SOCIAL & EMOT DEV SECT,9190 ROCKVILLE PIKE,BSA BLDG,RM 331,BETHESDA,MD 20814, USA. NR 114 TC 28 Z9 28 U1 2 U2 7 PU NATL COUNC FAMILY RELATIONS PI MINNEAPOLIS PA 3989 CENTRAL AVE NE #550, MINNEAPOLIS, MN 55421 SN 0197-6664 J9 FAM RELAT JI Fam. Relat. PD OCT PY 1991 VL 40 IS 4 BP 435 EP 441 DI 10.2307/584901 PG 7 WC Family Studies; Social Work SC Family Studies; Social Work GA GL741 UT WOS:A1991GL74100011 ER PT J AU SIEGALL, CB EPSTEIN, S SPEIR, E HLA, T FOROUGH, R MACIAG, T FITZGERALD, DJ PASTAN, I AF SIEGALL, CB EPSTEIN, S SPEIR, E HLA, T FOROUGH, R MACIAG, T FITZGERALD, DJ PASTAN, I TI CYTOTOXIC ACTIVITY OF CHIMERIC PROTEINS COMPOSED OF ACIDIC FIBROBLAST GROWTH-FACTOR AND PSEUDOMONAS EXOTOXIN ON A VARIETY OF CELL-TYPES SO FASEB JOURNAL LA English DT Note DE AFGF; TOXIN; CYTOTOXICITY; CHIMERIC; ANTIANGIOGENIC ID RECOMBINANT FUSION PROTEIN; CYTO-TOXIC ACTIVITY; ENDOTHELIAL-CELLS; RECEPTOR-BINDING; ANIMAL TOXICITY; DOMAIN-I; SEQUENCE; FAMILY; ALPHA; GENE AB Chimeric proteins composed of acidic fibroblast growth factor (acidic FGF) and several forms of Pseudomonas exotoxin (PE) that cannot bind to the PE receptor have been produced in Escherichia coli by expressing chimeric genes in which DNA encoding acidic FGF is fused to various mutant forms of PE. These acidic FGF-PE fusion proteins were found to be cytotoxic to a variety of tumor cell lines including hepatocellular (PLC/PRF/5 and HEPG2), prostatic (LNCaP), colon (HT29), and breast (MCF-7) carcinomas at concentrations of 1-70 ng/ml. The cytotoxic effects of acidic FGF-PE were FGF-receptor specific as demonstrated by competition with excess acidic FGF and by showing that acidic FGF-PE bound to the FGF receptor with the same affinity as acidic FGF. Furthermore, the cell-killing activity of acidic FGF-PE was toxin-mediated, as an acidic FGF-PE mutant, which does not possess ADP-ribosylation activity, failed to kill cells. These findings demonstrate that acidic FGF-PE is a potent cytotoxic molecule that can be targeted to FGF receptor-bearing cells. Because acidic FGF is a potent angiogenic molecule, cytotoxic acidic FGF-PE chimeras may have utility as anti-angiogenic agents. These molecules could be helpful in determining the functional role of FGF receptors in cellular processes. C1 NCI,DIV CANC BIOL,MOLEC BIOL LAB,9000 ROCKVILLE PIKE,BLDG 37,ROOM 4E16,BETHESDA,MD 20892. NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. AMER RED CROSS,JEROME H HOLLAND LABS BIOMED SCI,MOLEC BIOL LAB,ROCKVILLE,MD 20855. RI Hla, Timothy/G-5873-2012 OI Hla, Timothy/0000-0001-8355-4065 FU NHLBI NIH HHS [HL 35627, HL-32348] NR 43 TC 33 Z9 33 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD OCT PY 1991 VL 5 IS 13 BP 2843 EP 2849 PG 7 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA GJ471 UT WOS:A1991GJ47100013 PM 1717336 ER PT J AU LESCH, KP AF LESCH, KP TI PSYCHOBIOLOGY OF OBSESSIVE-COMPULSIVE DISORDER SO FORTSCHRITTE DER NEUROLOGIE PSYCHIATRIE LA German DT Article ID GLUCOSE METABOLIC RATES; PANIC DISORDER; SEROTONIN FUNCTION; HEALTHY-SUBJECTS; CLOMIPRAMINE; ANXIETY; RECEPTOR; HYPOTHESIS; CHLOROPHENYLPIPERAZINE; FLUVOXAMINE AB The predominant psychobiological hypotheses regarding the pathophysiology of obsessive-compulsive disorder (OCD) are that a selective basal ganglia dysfunction and a dysregulation of one or several central serotonin (5-HT) subsystem are related to at least some aspects of the syndrome. Recent neuroanatomical, -pharmacological, and -ethological studies indicate a complex perceptual and cognitive role for the basal ganglia, particularly the striatum and the pallidum, in addition to the well-established motor functions. Obsessive-compulsive symptoms in syndromes with extrapyramidal-motor dysfunction, such as Gilles de la Tourette syndrome or Chorea minor (Sydenham), response to specific pharmacotherapy, behavioural therapy, and psychosurgery, as well as findings derived from brain imaging studies including positron emission tomography (PET) support the view of a frontal cortex/basal ganglia dysfunction in OCD. In addition, growing evidence suggests that potent inhibitors of 5-HT reuptake and other 5-HT subsystem-selective agents, such as the azapirones with partial agonist properties at the 5-HT1A receptor, are effective in OCD not only has improved the therapeutic perspective but may also reveal clues to the aetiopathogenesis of OCD. Much of this evidence has resulted from the discovery of multiple receptors and signal transduction pathways for 5-HT and from experiments relating the action of 5-HT receptor-selective agents to discrete effects in different subsystems. Among these 5-HT subsystems the 5-HT1D and 5-HT1A receptor-effector system complex appears to play a central role in the pathophysiology of OCD symptoms and the mechanism of action of antiobsessional drugs. Recent psychoneurobiological findings are reviewed briefly and evaluated in the context of the 5-HT and basal ganglia hypothesis of OCD. RP LESCH, KP (reprint author), NIMH,CTR CLIN,CLIN SCI LAB,10-3D41,BETHESDA,MD 20892, USA. RI Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X NR 76 TC 10 Z9 10 U1 1 U2 1 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0720-4299 J9 FORTSCHR NEUROL PSYC JI Forschritte Neurol. Psychiatr. PD OCT PY 1991 VL 59 IS 10 BP 404 EP 412 DI 10.1055/s-2007-1000715 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA HH035 UT WOS:A1991HH03500002 PM 1761269 ER PT J AU MCCONNELL, EE HUFF, JE HEJTMANCIK, M PETERS, AC PERSING, R AF MCCONNELL, EE HUFF, JE HEJTMANCIK, M PETERS, AC PERSING, R TI TOXICOLOGY AND CARCINOGENESIS STUDIES OF 2 GRADES OF PENTACHLOROPHENOL IN B6C3F1-MICE SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID DIBENZO-PARA-DIOXINS; ANIMAL CARCINOGENICITY; UNITED-STATES; RATS; CHEMICALS; NEOPLASMS C1 BATTELLE MEM INST,COLUMBUS LABS,COLUMBUS,OH. NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. NR 65 TC 45 Z9 50 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD OCT PY 1991 VL 17 IS 3 BP 519 EP 532 DI 10.1016/0272-0590(91)90202-F PG 14 WC Toxicology SC Toxicology GA GL283 UT WOS:A1991GL28300009 PM 1794655 ER PT J AU KOPPSCHNEIDER, A PORTIER, CJ AF KOPPSCHNEIDER, A PORTIER, CJ TI DISTINGUISHING BETWEEN MODELS OF CARCINOGENESIS - THE ROLE OF CLONAL EXPANSION SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID CANCER RISK MODELS; TUMOR ONSET; CELL-PROLIFERATION; BLADDER-CANCER; 2-STAGE MODEL; EPIDEMIOLOGY; AGENTS; RAT C1 NIEHS,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709. RP KOPPSCHNEIDER, A (reprint author), DEUTSCH KREBSFORSCHUNGSZENTRUM,INST EPIDEMIOL & BIOMET,BIOSTAT ABT,NEUENHEIMER FELD 280,W-6900 HEIDELBERG,GERMANY. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 40 TC 20 Z9 20 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 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD OCT PY 1991 VL 17 IS 3 BP 601 EP 613 DI 10.1016/0272-0590(91)90210-U PG 13 WC Toxicology SC Toxicology GA GL283 UT WOS:A1991GL28300017 PM 1794662 ER PT J AU KUHN, GO MCCAMPBELL, P SINGMASTER, G ARNESON, DW JAMESON, CW AF KUHN, GO MCCAMPBELL, P SINGMASTER, G ARNESON, DW JAMESON, CW TI APPLICATION OF MICROENCAPSULATION TECHNOLOGY TO IMPROVE THE STABILITY OF CITRAL IN RODENT DIETS SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Note C1 NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. RP KUHN, GO (reprint author), MIDWEST RES INST,KANSAS CITY,MO 64110, USA. FU NIEHS NIH HHS [N01 ES 40560] NR 11 TC 8 Z9 8 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD OCT PY 1991 VL 17 IS 3 BP 635 EP 640 DI 10.1016/0272-0590(91)90213-N PG 6 WC Toxicology SC Toxicology GA GL283 UT WOS:A1991GL28300020 PM 1794663 ER PT J AU SARGE, KD ZIMARINO, V HOLM, K WU, C MORIMOTO, RI AF SARGE, KD ZIMARINO, V HOLM, K WU, C MORIMOTO, RI TI CLONING AND CHARACTERIZATION OF 2 MOUSE HEAT-SHOCK FACTORS WITH DISTINCT INDUCIBLE AND CONSTITUTIVE DNA-BINDING ABILITY SO GENES & DEVELOPMENT LA English DT Article DE MOUSE; HEAT SHOCK FACTOR; INDUCIBLE ID HSP70 GENE; TRANSCRIPTION FACTOR; YEAST; PROTEIN; EXPRESSION; CELLS; ACTIVATOR; SEQUENCE AB We have cloned two distinct mouse heat shock transcription factor genes, mHSF1 and mHSF2. The mHSF1 and mHSF2 open reading frames are similar in size, containing 503 and 517 amino acids, respectively. Although mHSF1 and mHSF2 are quite divergent overall (only 38% identity), they display extensive homology in the DNA-binding and oligomerization domains that are conserved in the heat shock factors of Saccharomyces cerevisiae, Kluyveromyces lactis, Drosophila, tomato, and human. The ability of these two mouse heat shock factors to bind to the heat shock element (HSE) is regulated by heat. mHSF1 is expressed in an in vitro translation system in an inactive form that is activated to DNA binding by incubation at temperatures > 41-degrees-C, the same temperatures that activate heat shock factor DNA binding and the stress response in mouse cells in vivo. mHSF2, on the other hand, is expressed in a form that binds DNA constitutively but loses DNA binding by incubation at > 41-degrees-C. Both mHSF1 and mHSF2 are encoded by single-copy genes, and neither is transcriptionally regulated by heat shock. However, there is a striking difference in the levels of mHSF1 mRNA in different tissues of the mouse. C1 NORTHWESTERN UNIV,DEPT BIOCHEM MOLEC BIOL & CELL BIOL,EVANSTON,IL 60208. NCI,BIOCHEM LAB,BETHESDA,MD 20892. UNIV COPENHAGEN,INST MICROBIOL,DK-1168 COPENHAGEN,DENMARK. NR 25 TC 303 Z9 311 U1 1 U2 4 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 OCT PY 1991 VL 5 IS 10 BP 1902 EP 1911 DI 10.1101/gad.5.10.1902 PG 10 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA GJ654 UT WOS:A1991GJ65400017 PM 1717345 ER PT J AU SCHAAPER, RM DUNN, RL AF SCHAAPER, RM DUNN, RL TI SPONTANEOUS MUTATION IN THE ESCHERICHIA-COLI LACI GENE SO GENETICS LA English DT Article ID DNA MISMATCH CORRECTION; NON-ENZYMATIC METHYLATION; SPONTANEOUS MUTAGENESIS; DEOXYRIBONUCLEIC-ACID; CYTOSINE RESIDUES; REPAIR; POLYMERASE; REPLICATION; SPECIFICITY; REPRESSOR AB To gain more detailed insight into the nature and mechanisms of spontaneous mutations, we undertook a DNA sequence analysis of a large collection of spontaneous mutations in the N-terminal region of the Escherichia coli lacI gene. This region of circa 210 base pairs is the target for dominant lacI mutations (i(-d) and is suitable for studies of mutational specificity since it contains a relatively high density of detectable mutable sites. Among 414 independent i(-d) mutants, 70.8% were base substitutions, 17.2% deletions, 7.7% additions and 4.3% single-base frameshifts. The base substitutions were both transitions (60%) and transversions (40%), the largest single group being G.C --> A.T (47% of base substitutions). All four transversions were observed. Among the 71 deletions, a hotspot (37 mutants) was present: an 87-bp deletion presumably directed by an 8-bp repeated sequence at its endpoints. The remaining 34 deletions were distributed among 29 different mutations, either flanked (13/34) or not flanked (21/34) by repeated sequences. The 32 additions comprised 29 different events, with only two containing a direct repeat at the endpoints. The single-base frameshifts were the loss of a single base from either repeated (67%) or nonrepeated (33%) bases. A comparison with the spectrum obtained previously in strains defective in DNA mismatch correction (mutH, mutL, mutS strains) yielded information about the apparent efficiency of mismatch repair. The overall effect was 260-fold but varied substantially among different classes of mutations. An interesting asymmetry was uncovered for the two types of transitions, A.T --> G.C and G.C --> A.T being reduced by mismatch repair 1340- and 190-fold, respectively. Explanations for this asymmetry and its possible implications for the origins of spontaneous mutations are discussed. RP SCHAAPER, RM (reprint author), NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709, USA. NR 67 TC 166 Z9 168 U1 1 U2 7 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD OCT PY 1991 VL 129 IS 2 BP 317 EP 326 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA GH445 UT WOS:A1991GH44500002 PM 1660424 ER PT J AU OETTINGER, HF STREETER, H LOSE, E COPELAND, NG GILBERT, DJ JUSTICE, MJ JENKINS, NA MOHANDAS, T BERNFIELD, M AF OETTINGER, HF STREETER, H LOSE, E COPELAND, NG GILBERT, DJ JUSTICE, MJ JENKINS, NA MOHANDAS, T BERNFIELD, M TI CHROMOSOME MAPPING OF THE MURINE SYNDECAN GENE SO GENOMICS LA English DT Article ID CELL-SURFACE PROTEOGLYCAN; MAMMARY EPITHELIAL-CELLS; HEPARAN-SULFATE PROTEOGLYCANS; EXPRESSION; MYC; LOCALIZATION; STABILITY; RECEPTOR; MATRIX; LOCI C1 HARVARD UNIV,SCH MED,JOINT PROGRAM NEONATOL,BOSTON,MA 02115. UNIV CALIF LOS ANGELES,LOS ANGELES CTY HARBOR MED CTR,DIV MED GENET,TORRANCE,CA 90509. NCI,FCRDC,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [1F32CA08853, CA28735]; PHS HHS [N01-C0-74101] NR 21 TC 20 Z9 20 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 OCT PY 1991 VL 11 IS 2 BP 334 EP 338 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA GE394 UT WOS:A1991GE39400013 PM 1769649 ER PT J AU LEVINE, MA MODI, WS OBRIEN, SJ AF LEVINE, MA MODI, WS OBRIEN, SJ TI MAPPING OF THE GENE ENCODING THE ALPHA-SUBUNIT OF THE STIMULATORY-G PROTEIN OF ADENYLYL CYCLASE (GNAS1) TO 20Q13.2-]Q13.3 IN HUMAN BY INSITU HYBRIDIZATION SO GENOMICS LA English DT Note ID HEREDITARY OSTEODYSTROPHY; MUTATIONS; MOUSE C1 NCI,FREDERICK CANC RES FACIL,BIOL CARCINOGENESIS & DEV PROGRAM,PROGRAM RESOURCES INC,FREDERICK,MD 21701. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. RP LEVINE, MA (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV BIOPHYS,HUNTERIAN BLDG,ROOM 816,725 N WOLFE ST,BALTIMORE,MD 21205, USA. OI Levine, Michael/0000-0003-0036-7809 FU NIDDK NIH HHS [DK34281] NR 11 TC 55 Z9 56 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 OCT PY 1991 VL 11 IS 2 BP 478 EP 479 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA GE394 UT WOS:A1991GE39400037 PM 1769666 ER PT J AU JENKINS, NA MATTEI, MG GILBERT, DJ LINARD, CG MBIKAY, M CHRETIEN, M COPELAND, NG AF JENKINS, NA MATTEI, MG GILBERT, DJ LINARD, CG MBIKAY, M CHRETIEN, M COPELAND, NG TI ASSIGNMENT OF SECRETOGRANIN-1 LOCUS TO MOUSE CHROMOSOME-2 BY INSITU HYBRIDIZATION AND INTERSPECIFIC BACKCROSS ANALYSIS SO GENOMICS LA English DT Note ID CHROMOGRANIN-B; LOCALIZATION C1 UNIV MONTREAL,INST RECH CLIN MONTREAL,JA SEVE NEUROENDOCRINOL MOLEC LAB,MONTREAL H2W 1R7,QUEBEC,CANADA. HOP ENFANTS LA TIMONE,CTR GENET MED,INSERM,U242,F-13385 MARSEILLE 5,FRANCE. RP JENKINS, NA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702, USA. OI MBIKAY, Majambu/0000-0003-4854-6507 FU NCI NIH HHS [N01-CO-74101] NR 9 TC 7 Z9 7 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 OCT PY 1991 VL 11 IS 2 BP 479 EP 480 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA GE394 UT WOS:A1991GE39400038 PM 1685143 ER PT J AU WARNER, HR BAKER, GT AF WARNER, HR BAKER, GT TI ANNUAL-REVIEW OF GERONTOLOGY AND GERIATRICS, VOL 10 - CRISTOFALO,VJ SO GERONTOLOGIST LA English DT Book Review C1 NATHAN SHOCK AGING RES FDN,SILVER SPRING,MD 20951. RP WARNER, HR (reprint author), NIA,BIOL AGING PROGRAM,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 1 U2 1 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 OCT PY 1991 VL 31 IS 5 BP 704 EP 706 PG 3 WC Gerontology SC Geriatrics & Gerontology GA GJ744 UT WOS:A1991GJ74400023 ER PT J AU CHESON, BD AF CHESON, BD TI NEW CHEMOTHERAPEUTIC-AGENTS FOR NON-HODGKINS-LYMPHOMAS SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID PHASE-II TRIAL; SOUTHWEST-ONCOLOGY-GROUP; ADVANCED MALIGNANT-LYMPHOMA; LEUKEMIA GROUP-B; CHRONIC LYMPHOCYTIC-LEUKEMIA; DOSE CYTOSINE-ARABINOSIDE; HAIRY-CELL LEUKEMIA; FLUDARABINE PHOSPHATE THERAPY; PREVIOUSLY TREATED PATIENTS; REFRACTORY LYMPHOMA RP CHESON, BD (reprint author), NCI,DIV CANC TREATMENT,CLIN INVEST BRANCH,MED SECT,CANC THERAPY EVALUAT PROGRAM,EXECUT PLAZA N,BETHESDA,MD 20892, USA. NR 136 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 1991 VL 5 IS 5 BP 1027 EP 1051 PG 25 WC Oncology; Hematology SC Oncology; Hematology GA GF402 UT WOS:A1991GF40200013 PM 1718938 ER PT J AU LONGO, DL AF LONGO, DL TI BIOLOGIC AGENTS AND APPROACHES IN THE MANAGEMENT OF PATIENTS WITH LYMPHOMA - A CRITICAL-APPRAISAL SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID NON-HODGKINS-LYMPHOMA; T-CELL LYMPHOMA; BONE-MARROW TRANSPLANTATION; COLONY-STIMULATING FACTOR; ANTI-IDIOTYPE ANTIBODIES; ACTIVATED KILLER-CELLS; GROWTH FACTOR-BETA; CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; HIGH-DOSE THERAPY RP LONGO, DL (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,BLDG 576,FREDERICK,MD 21702, USA. NR 96 TC 9 Z9 9 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 1991 VL 5 IS 5 BP 1067 EP 1087 PG 21 WC Oncology; Hematology SC Oncology; Hematology GA GF402 UT WOS:A1991GF40200015 PM 1718939 ER PT J AU CARBONE, D AF CARBONE, D TI FOCUSING IN ON P53 IN HEPATOCELLULAR-CARCINOMA SO HEPATOLOGY LA English DT Note ID CANCER; GENE; MUTATIONS; PROTEIN RP CARBONE, D (reprint author), USN HOSP BETHESDA,NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20889, USA. NR 12 TC 2 Z9 2 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 OCT PY 1991 VL 14 IS 4 BP 742 EP 744 DI 10.1016/0270-9139(91)90071-3 PN 1 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GH580 UT WOS:A1991GH58000029 PM 1655609 ER PT J AU ALAM, K BATRA, SK DEKOVICH, AA GUBBINS, G SHIH, JW KRAWCZYNSKI, K MOZES, M AF ALAM, K BATRA, SK DEKOVICH, AA GUBBINS, G SHIH, JW KRAWCZYNSKI, K MOZES, M TI RECURRENCE OF HEPATITIS-C VIRUS-INFECTION AFTER ORTHOTOPIC LIVER-TRANSPLANTATION - A CASE-REPORT SO HEPATOLOGY LA English DT Meeting Abstract C1 HENRY FORD HOSP,DIV GASTROENTEROL & TRANSPLANT SURG,DETROIT,MI 48202. NIH,TRANFUS TRANSMITTED VIRUS LAB,BETHESDA,MD 20892. CTR DIS CONTROL,HEPATITIS BRANCH,ATLANTA,GA 30333. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1991 VL 14 IS 4 BP A278 EP A278 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GK111 UT WOS:A1991GK11100920 ER PT J AU BERGASA, NV ROTHMAN, RB VERGALLA, J SWAIN, MG XU, H JONES, EA AF BERGASA, NV ROTHMAN, RB VERGALLA, J SWAIN, MG XU, H JONES, EA TI GLOBAL DOWN-REGULATION OF MU-OPIOID RECEPTORS IN ACUTE CHOLESTASIS IN RATS - FURTHER EVIDENCE FOR ALTERED STATUS OF THE CENTRAL OPIOID SYSTEM SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH,LIVER DIS SECT,BETHESDA,MD 20892. NIDA,ADDICT RES CTR,LEXINGTON,KY 40583. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1991 VL 14 IS 4 BP A249 EP A249 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GK111 UT WOS:A1991GK11100804 ER PT J AU BERGASA, NV ALLING, DW TALBOT, TL SCHMITT, JP SWAIN, MG FONG, TL FRIED, MW JONES, EA AF BERGASA, NV ALLING, DW TALBOT, TL SCHMITT, JP SWAIN, MG FONG, TL FRIED, MW JONES, EA TI RELIEF FROM THE INTRACTABLE PRURITUS OF CHRONIC CHOLESTASIS ASSOCIATED WITH ORAL NALMEFENE THERAPY SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LIVER DIS SECT,BETHESDA,MD. NIAID,BETHESDA,MD 20892. ACES,BETHESDA,MD. NR 3 TC 11 Z9 11 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 OCT PY 1991 VL 14 IS 4 BP A154 EP A154 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GK111 UT WOS:A1991GK11100425 ER PT J AU BUKH, J PURCELL, RH MILLER, RH AF BUKH, J PURCELL, RH MILLER, RH TI THE IMPORTANCE OF PRIMER SELECTION FOR THE DETECTION OF HEPATITIS-C VIRUS (HCV) RNA BY PCR SO HEPATOLOGY LA English DT Meeting Abstract C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1991 VL 14 IS 4 BP A116 EP A116 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GK111 UT WOS:A1991GK11100272 ER PT J AU BUKH, J WANTZIN, P KROGSGAARD, K KNUDSEN, F MILLER, RH PURCELL, RH AF BUKH, J WANTZIN, P KROGSGAARD, K KNUDSEN, F MILLER, RH PURCELL, RH TI HCV VIREMIA IN ANTI-HCV POSITIVE DIALYSIS PATIENTS - POOR CORRELATION OF RIBA TEST-RESULTS WITH THE PRESENCE OF HCV RNA SO HEPATOLOGY LA English DT Meeting Abstract C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. HVIDOVRE UNIV HOSP,DEPT CLIN IMMUNOL,DK-2650 HVIDOVRE,DENMARK. RIGSHOSP,DEPT INFECT DIS,DK-2100 COPENHAGEN,DENMARK. HERLEV HOSP,DEPT NEPHROL,DK-2730 HERLEV,DENMARK. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1991 VL 14 IS 4 BP A81 EP A81 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GK111 UT WOS:A1991GK11100135 ER PT J AU DIBISCEGLIE, AM BERGASA, NV FONG, TL FRIED, MW SWAIN, M BAKER, B KORENMAN, J WAGGONER, JG PARK, Y HOOFNAGLE, JH AF DIBISCEGLIE, AM BERGASA, NV FONG, TL FRIED, MW SWAIN, M BAKER, B KORENMAN, J WAGGONER, JG PARK, Y HOOFNAGLE, JH TI A RANDOMIZED, CONTROLLED TRIAL OF RECOMBINANT ALPHA-INTERFERON THERAPY FOR CHRONIC HEPATITIS-B SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH,LIVER DIS SECT,BETHESDA,MD 20892. NR 0 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1991 VL 14 IS 4 BP A70 EP A70 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GK111 UT WOS:A1991GK11100090 ER PT J AU ESTEBAN, JI GONZALEZ, A VILADOMIU, L MADOZ, P ENRIQUEZ, J GENESCA, J QUER, J HOUGHTON, M SHIH, JWK ALTER, HJ ESTEBAN, R GUARDIA, J AF ESTEBAN, JI GONZALEZ, A VILADOMIU, L MADOZ, P ENRIQUEZ, J GENESCA, J QUER, J HOUGHTON, M SHIH, JWK ALTER, HJ ESTEBAN, R GUARDIA, J TI OPEN PROSPECTIVE EFFICACY TRIAL OF ANTI-HCV SCREENING OF BLOOD-DONORS TO PREVENT TRANSFUSION-ASSOCIATED HEPATITIS SO HEPATOLOGY LA English DT Meeting Abstract C1 HOSP GEN VALLE HEBRON,BLOOD BANK,LIVER UNIT,BARCELONA,SPAIN. HOSP SANTA CRUZ & SAN PABLO,GASTROENTEROL UNIT,BARCELONA,SPAIN. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. CHIRON CORP,EMERYVILLE,CA. RI Quer, Josep/A-6741-2012 NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1991 VL 14 IS 4 BP A94 EP A94 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GK111 UT WOS:A1991GK11100184 ER PT J AU FARCI, P ALTER, HJ OGATA, N WONG, D ENGLE, R MILLER, R DAWSON, G LESMIEWSKI, R MUSHAHWAR, I PURCELL, R AF FARCI, P ALTER, HJ OGATA, N WONG, D ENGLE, R MILLER, R DAWSON, G LESMIEWSKI, R MUSHAHWAR, I PURCELL, R TI LACK OF PROTECTION AGAINST REINFECTION WITH HEPATITIS-C VIRUS (HCV) IN MULTIPLE CROSS-CHALLENGES OF CHIMPANZEES SO HEPATOLOGY LA English DT Meeting Abstract C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. GEORETOWN UNIV,DMVI,ROCKVILLE,MD. ABBOTT LABS,N CHICAGO,IL 60064. NR 0 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1991 VL 14 IS 4 BP A90 EP A90 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GK111 UT WOS:A1991GK11100171 ER PT J AU FONG, TL DIBISCEGLIE, AM FEINSTONE, SM WAGGONER, JG AXIOTIS, CA HOOFNAGLE, JH AF FONG, TL DIBISCEGLIE, AM FEINSTONE, SM WAGGONER, JG AXIOTIS, CA HOOFNAGLE, JH TI PERSISTENT HEPATIC HBV-DNA AFTER CLEARANCE OF HBSAG FROM SERUM OF PATIENTS WITH CHRONIC HEPATITIS-B SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. US FDA,BETHESDA,MD 20014. NR 0 TC 7 Z9 7 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 OCT PY 1991 VL 14 IS 4 BP A130 EP A130 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GK111 UT WOS:A1991GK11100331 ER PT J AU FRIED, MW SWAIN, MG FONG, TL HAVORKA, R RUDDEL, M BARNETT, JA HOOFNAGLE, JH DIBISCEGLIE, AM JONES, EA AF FRIED, MW SWAIN, MG FONG, TL HAVORKA, R RUDDEL, M BARNETT, JA HOOFNAGLE, JH DIBISCEGLIE, AM JONES, EA TI THE MONOETHYLGLYCINEXYLIDIDE (MEGX) TEST OF HEPATIC-FUNCTION IN CHRONIC VIRAL-HEPATITIS SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. CITY UNIV LONDON,LONDON EC1V 0HB,ENGLAND. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1991 VL 14 IS 4 BP A271 EP A271 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GK111 UT WOS:A1991GK11100892 ER PT J AU FRIED, MW DRAQUESKU, J SHINDO, M SIMPSON, LH GRACEY, D BANKS, SM HOOFNAGLE, JH DIBISCEGLIE, AM AF FRIED, MW DRAQUESKU, J SHINDO, M SIMPSON, LH GRACEY, D BANKS, SM HOOFNAGLE, JH DIBISCEGLIE, AM TI COMPARISON OF AUTOIMMUNE (AI) AND HEPATITIS-C VIRUS (HCV) RELATED CHRONIC HEPATITIS SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. UNIV SO CALIF,LOS ANGELES,CA 90089. NR 0 TC 2 Z9 2 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 OCT PY 1991 VL 14 IS 4 BP A61 EP A61 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GK111 UT WOS:A1991GK11100055 ER PT J AU HOLLINGER, FB STEVENS, CE AACH, RD PETERSON, DA BARBOSA, LH NEMO, GJ MOSLEY, JW AF HOLLINGER, FB STEVENS, CE AACH, RD PETERSON, DA BARBOSA, LH NEMO, GJ MOSLEY, JW TI WILL RECIPIENTS OF ANTI-HCV SCREENED DONOR BLOOD REMAIN AT RISK FOR CHRONIC HEPATITIS AND SHOULD DONORS CONTINUE TO BE SCREENED FOR ALT AND ANTI-HBC SO HEPATOLOGY LA English DT Meeting Abstract C1 BAYLOR COLL MED,HOUSTON,TX 77030. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. UNIV SO CALIF,LOS ANGELES,CA 90089. ABBOTT LABS,N CHICAGO,IL 60064. NHLBI,BETHESDA,MD 20892. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1991 VL 14 IS 4 BP A128 EP A128 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GK111 UT WOS:A1991GK11100323 ER PT J AU HSIA, CC AXIOTIS, CA DIBISCEGLIE, AM TABOR, E AF HSIA, CC AXIOTIS, CA DIBISCEGLIE, AM TABOR, E TI COEXPRESSION OF TRANSFORMING GROWTH FACTOR-ALPHA AND HEPATITIS-B SURFACE-ANTIGEN IN THE SAME HEPATOCYTES OF HUMAN LIVER-TISSUE ADJACENT TO HEPATOCELLULAR-CARCINOMA SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NIH,CTR CLIN,BETHESDA,MD 20892. NIDDK,BETHESDA,MD. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1991 VL 14 IS 4 BP A109 EP A109 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GK111 UT WOS:A1991GK11100247 ER PT J AU LATHAM, PS GUSELLA, GL SMITH, GL DEVOR, DE VARESIO, L WARD, JM AF LATHAM, PS GUSELLA, GL SMITH, GL DEVOR, DE VARESIO, L WARD, JM TI CHARACTERIZATION OF A UNIQUE TUMOR-DERIVED MACROPHAGE CELL-LINE OF A PRIMARY LIVER HISTIOCYTIC SARCOMA SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI,BCD-PRI DYNCORP,MOLEC IMMUNOREGULAT LABS,FREDERICK,MD 21702. RI varesio, luigi/J-8261-2016 OI varesio, luigi/0000-0001-5659-2218 NR 0 TC 2 Z9 2 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 OCT PY 1991 VL 14 IS 4 BP A168 EP A168 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GK111 UT WOS:A1991GK11100480 ER PT J AU LEE, JH ZELDIS, JB BAKER, B WAGGONER, JG DIBISCEQLIE, AM AF LEE, JH ZELDIS, JB BAKER, B WAGGONER, JG DIBISCEQLIE, AM TI A NOVEL NON-SENSE MUTATION IN THE PRE-C-REGION OF HEPATITIS-B VIRUS (HBV) ASSOCIATED WITH CLEARANCE OF HEPATITIS-B E-ANTIGEN AND PROGRESSIVE LIVER-DISEASE SO HEPATOLOGY LA English DT Meeting Abstract C1 UNIV CALIF DAVIS,SACRAMENTO MED CTR,GASTROINTESTINAL SECT,SACRAMENTO,CA 95817. NIH,LIVER DIS SECT,BETHESDA,MD 20892. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1991 VL 14 IS 4 BP A77 EP A77 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GK111 UT WOS:A1991GK11100116 ER PT J AU NAKATSUKASA, H EVARTS, RP SILVERMAN, J THORGEIRSSON, SS AF NAKATSUKASA, H EVARTS, RP SILVERMAN, J THORGEIRSSON, SS TI EXPRESSION OF MULTIDRUG RESISTANCE AND GLUTATHIONE TRANSFERASE-PLACENTAL FORM GENES DURING CHEMICAL HEPATOCARCINOGENESIS IN RAT-LIVER SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1991 VL 14 IS 4 BP A108 EP A108 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GK111 UT WOS:A1991GK11100240 ER PT J AU NEGRO, F PACCHIONI, D MILLER, RH SHIMIZU, Y BUSSOLATI, G PURCELL, RH BONINO, F AF NEGRO, F PACCHIONI, D MILLER, RH SHIMIZU, Y BUSSOLATI, G PURCELL, RH BONINO, F TI INTRAHEPATIC REPLICATION OF HEPATITIS-C VIRUS IN THE CHIMPANZEE AS DETECTED BY INSITU HYBRIDIZATION SO HEPATOLOGY LA English DT Meeting Abstract C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. MOLINETTE MAURIZIANO HOSP,DEPT GASTROENTEROL,TURIN,ITALY. NATL INST HLTH,TOKYO 141,JAPAN. UNIV TURIN,I-10124 TURIN,ITALY. NR 0 TC 2 Z9 2 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 OCT PY 1991 VL 14 IS 4 BP A116 EP A116 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GK111 UT WOS:A1991GK11100274 ER PT J AU NOUSO, K BATTULA, N THORGEIRSSON, SS AF NOUSO, K BATTULA, N THORGEIRSSON, SS TI STABLE EXPRESSION OF HUMAN CYTOCHROME P450IIE1 IN MAMMALIAN-CELLS - METABOLIC-ACTIVATION OF NITROSODIMETHYLAMINE AND FORMATION OF ADDUCTS WITH CELLULAR DNA SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1991 VL 14 IS 4 BP A157 EP A157 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GK111 UT WOS:A1991GK11100437 ER PT J AU OKADA, Y TABOR, E AF OKADA, Y TABOR, E TI DETECTION OF HEPATITIS-B VIRUS (HBV) DNA-SEQUENCES IN SERUM FROM PATIENTS WITH HEPATOCELLULAR-CARCINOMA (HCC) USING STANDARD AND MODIFIED (MULTITARGET) POLYMERASE CHAIN-REACTION (PCR) METHODS SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1991 VL 14 IS 4 BP A107 EP A107 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GK111 UT WOS:A1991GK11100239 ER PT J AU PHILLIPS, MJ POUCELLHATTON, S PATTERSON, J BLENDIS, L LEVY, GA PURCELL, R AF PHILLIPS, MJ POUCELLHATTON, S PATTERSON, J BLENDIS, L LEVY, GA PURCELL, R TI VIRUS-MEMBRANE INTERACTIONS IN HEPATOCYTES OF SYNCYTIAL GIANT-CELL HEPATITIS SO HEPATOLOGY LA English DT Meeting Abstract C1 UNIV TORONTO,DEPT PATHOL,TORONTO M5S 1A1,ONTARIO,CANADA. UNIV TORONTO,DEPT MED,TORONTO M5S 1A1,ONTARIO,CANADA. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1991 VL 14 IS 4 BP A215 EP A215 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GK111 UT WOS:A1991GK11100670 ER PT J AU SHINDO, M FEINSTONE, SM DIBISCEGLIE, AM AF SHINDO, M FEINSTONE, SM DIBISCEGLIE, AM TI HEPATITIS-C VIRUS (HCV) RNA IN SERUM AND LIVER DURING ACUTE HCV INFECTION IN CHIMPANZEES SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. US FDA,BETHESDA,MD 20014. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1991 VL 14 IS 4 BP A118 EP A118 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GK111 UT WOS:A1991GK11100283 ER PT J AU SHINDO, M DIBISCEGLIER, AM SILVER, J LIMJOCO, T HOOFNAGLE, JH FEINSTONE, SM AF SHINDO, M DIBISCEGLIER, AM SILVER, J LIMJOCO, T HOOFNAGLE, JH FEINSTONE, SM TI QUANTITATION OF HEPATITIS-C VIRUS-RNA IN SERUM USING THE POLYMERASE CHAIN-REACTION AND A COLORIMETRIC ENZYMATIC DETECTION SYSTEM SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. US FDA,BETHESDA,MD 20014. NR 0 TC 2 Z9 2 U1 1 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 OCT PY 1991 VL 14 IS 4 BP A64 EP A64 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GK111 UT WOS:A1991GK11100068 ER PT J AU SHINDO, M MULLIN, GW BERGASA, NV JONES, EA JAMES, SP AF SHINDO, M MULLIN, GW BERGASA, NV JONES, EA JAMES, SP TI LACK OF CYTOKINE MESSENGER-RNA EXPRESSION IN THE LIVER OF PATIENTS WITH PRIMARY BILIARY-CIRRHOSIS SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LIVER DIS SECT,BETHESDA,MD. NIAID,MUCOSAL IMMUN SECT,BETHESDA,MD 20892. NR 0 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1991 VL 14 IS 4 BP A63 EP A63 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GK111 UT WOS:A1991GK11100061 ER PT J AU SJOGREN, MH PURCELL, RH MCKEE, K BINN, L MACARTHY, P LAKOVIC, M TICEHURST, J HOKE, C FEINSTONE, SM HONDT, ED BANCROFT, WH AF SJOGREN, MH PURCELL, RH MCKEE, K BINN, L MACARTHY, P LAKOVIC, M TICEHURST, J HOKE, C FEINSTONE, SM HONDT, ED BANCROFT, WH TI LIMITED REPLICATIVE CAPACITY OF A LIVE, ATTENUATED HEPATITIS-A VACCINE FOLLOWING ORAL IMMUNIZATION OF VOLUNTEERS SO HEPATOLOGY LA English DT Meeting Abstract C1 WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. NIH,BETHESDA,MD 20892. USA,MED RES INST INFECT DIS,FREDERICK,MD 21701. US FDA,BETHESDA,MD 20014. SMITHKLINE BEECHAM,RIXENSART,BELGIUM. RI Ticehurst, John/I-7532-2012 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1991 VL 14 IS 4 BP A219 EP A219 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GK111 UT WOS:A1991GK11100684 ER PT J AU SWAIN, MG VERGALLA, J BERGASA, NV JONES, EA AF SWAIN, MG VERGALLA, J BERGASA, NV JONES, EA TI CHANGES IN PLASMA AND WHOLE BRAIN LEVELS OF METHIONINE ENKEPHALIN IN RATS WITH ACUTE TOXIC HEPATITIS SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LIVER DIS SECT,BETHESDA,MD. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1991 VL 14 IS 4 BP A277 EP A277 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GK111 UT WOS:A1991GK11100918 ER PT J AU SWAIN, MG ROTHMAN, RB XU, H VERGALLA, J BERGASA, NV JONES, EA AF SWAIN, MG ROTHMAN, RB XU, H VERGALLA, J BERGASA, NV JONES, EA TI BRAIN LEVELS OF ENDOGENOUS OPIOIDS IN A RAT MODEL OF ACUTE CHOLESTASIS SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LIVER DIS SECT,BETHESDA,MD. NIDDK,LMC,BETHESDA,MD. NIDA,RES CTR,BALTIMORE,MD. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1991 VL 14 IS 4 BP A263 EP A263 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GK111 UT WOS:A1991GK11100859 ER PT J AU SWAIN, MG VERGALLA, J BERGASA, NV JONES, EA AF SWAIN, MG VERGALLA, J BERGASA, NV JONES, EA TI ACUTE CHOLESTASIS IN RATS IS ASSOCIATED WITH OPIOID-MEDIATED SUPPRESSION OF STRESS-INDUCED ACTH RELEASE SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LIVER DIS SECT,BETHESDA,MD. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1991 VL 14 IS 4 BP A154 EP A154 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GK111 UT WOS:A1991GK11100427 ER PT J AU TABOR, E CAIRNS, J GERETY, RJ BAYLEY, AC AF TABOR, E CAIRNS, J GERETY, RJ BAYLEY, AC TI HEPATITIS-B VACCINE TRIAL - PREVALENCE OF PROTECTIVE ANTIBODY 9 YEARS LATER SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. ST FRANCIS HOSP,KATETE,ZAMBIA. BIOGEN INC,CAMBRIDGE,MA. DEPT SURG,LUSAKA,ZAMBIA. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1991 VL 14 IS 4 BP A220 EP A220 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GK111 UT WOS:A1991GK11100689 ER PT J AU YURDAYDIN, C FROMM, C HOLT, AG BASILE, AS AF YURDAYDIN, C FROMM, C HOLT, AG BASILE, AS TI MODULATION OF HEPATIC-ENCEPHALOPATHY (HE) BY BENZODIAZEPINE RECEPTOR (BZR) LIGANDS IS SELECTIVE SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK,LIVER DIS SECT,BETHESDA,MD. NIDDK,NEUROSCI LAB,BETHESDA,MD. NR 0 TC 2 Z9 2 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 OCT PY 1991 VL 14 IS 4 BP A89 EP A89 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GK111 UT WOS:A1991GK11100166 ER PT J AU LYONS, JS OMAHONEY, MT LARSON, DB AF LYONS, JS OMAHONEY, MT LARSON, DB TI THE ATTENDING PSYCHIATRIST AS A PREDICTOR OF LENGTH OF STAY SO HOSPITAL AND COMMUNITY PSYCHIATRY LA English DT Note ID CARE C1 MERCY CTR,PSYCHIAT SERV,AURORA,IL. NIMH,ROCKVILLE,MD 20857. RP LYONS, JS (reprint author), NORTHWESTERN UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,WARD BLDG,12-138,303 E CHICAGO AVE,CHICAGO,IL 60611, USA. NR 10 TC 20 Z9 20 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0022-1597 J9 HOSP COMMUNITY PSYCH PD OCT PY 1991 VL 42 IS 10 BP 1064 EP 1066 PG 3 WC Public, Environmental & Occupational Health; Psychiatry SC Public, Environmental & Occupational Health; Psychiatry GA GH373 UT WOS:A1991GH37300014 PM 1959901 ER PT J AU BARR, RA EBERHARD, JW AF BARR, RA EBERHARD, JW TI SAFETY AND MOBILITY OF ELDERLY DRIVERS, .1. PREFACE SO HUMAN FACTORS LA English DT Article C1 NATL HIGHWAY TRAFF SAFETY ADM,WASHINGTON,DC. RP BARR, RA (reprint author), NIA,BLDG 31,ROOM 4C32,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMAN FACTORS SOC PI SANTA MONICA PA BOX 1369, SANTA MONICA, CA 90406 SN 0018-7208 J9 HUM FACTORS JI Hum. Factors PD OCT PY 1991 VL 33 IS 5 BP 497 EP 498 PG 2 WC Behavioral Sciences; Engineering, Industrial; Ergonomics; Psychology, Applied; Psychology SC Behavioral Sciences; Engineering; Psychology GA GQ075 UT WOS:A1991GQ07500001 ER PT J AU BARR, RA AF BARR, RA TI RECENT CHANGES IN DRIVING AMONG OLDER ADULTS SO HUMAN FACTORS LA English DT Article ID AGE AB Driving statistics comparing drivers aged at least 65 years with all drivers are examined for the years 1980 and 1989. In that time older driver fatalities had increased substantially despite a decrease in total driver fatalities. Analyses of size of population, numbers of licensed drivers, estimates of miles driven, and crash rates for these two years imply that the rise in total older driver deaths is related to increasing numbers of older adults who are licensed to drive and an increase in likelihood of fatality following a motor vehicle crash. This latter effect may be associated with a very substantial rise in the numbers of licensed drivers age 70 and older. RP BARR, RA (reprint author), NIA,GATEWAY BLDG,RM 2C-234,7201 WISCONSIN AVE,BETHESDA,MD 20892, USA. NR 11 TC 22 Z9 22 U1 0 U2 1 PU HUMAN FACTORS SOC PI SANTA MONICA PA BOX 1369, SANTA MONICA, CA 90406 SN 0018-7208 J9 HUM FACTORS JI Hum. Factors PD OCT PY 1991 VL 33 IS 5 BP 597 EP 600 PG 4 WC Behavioral Sciences; Engineering, Industrial; Ergonomics; Psychology, Applied; Psychology SC Behavioral Sciences; Engineering; Psychology GA GQ075 UT WOS:A1991GQ07500010 PM 1769678 ER EF