FN Thomson Reuters Web of Science™ VR 1.0 PT J AU RUBIN, JS BOTTARO, DP AARONSON, SA AF RUBIN, JS BOTTARO, DP AARONSON, SA TI HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR AND ITS RECEPTOR, THE C-MET PROTOONCOGENE PRODUCT SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Review ID FULMINANT HEPATIC-FAILURE; TYROSINE KINASE-ACTIVITY; ADULT-RAT HEPATOCYTES; CARCINOMA CELL-LINE; ANCHORAGE-INDEPENDENT GROWTH; HUMAN GASTRIC-CARCINOMA; FACTOR HEPATOPOIETIN-A; HUMAN SKIN FIBROBLASTS; FACTOR GENE-EXPRESSION; FACTOR MESSENGER-RNA RP RUBIN, JS (reprint author), NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892, USA. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 192 TC 274 Z9 280 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD DEC 23 PY 1993 VL 1155 IS 3 BP 357 EP 371 DI 10.1016/0304-419X(93)90015-5 PG 15 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MQ146 UT WOS:A1993MQ14600007 PM 8268192 ER PT J AU SAGIE, A LARSON, MG LEVY, D AF SAGIE, A LARSON, MG LEVY, D TI THE NATURAL-HISTORY OF BORDERLINE ISOLATED SYSTOLIC HYPERTENSION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BLOOD-PRESSURE; MEN; RISK; DISEASE; TRIAL; DEATH AB Background. Patients with isolated systolic hypertension are at increased risk for cardiovascular disorders. We attempted to determine whether those with borderline isolated systolic hypertension (defined as a systolic blood pressure of 140 to 159 mm Hg and a diastolic blood pressure below 90 mm Hg) have a greater risk of progression to definite (more severe) hypertension and of major morbid or fatal events than people with normal blood pressure (<140/90 mm Hg). Methods. A total of 2767 of the original participants in the Framingham Heart Study were monitored with biennial examinations for up to 34 years for the development of definite hypertension (defined as a systolic blood pressure of greater-than-or-equal-to 160 mm Hg, a diastolic blood pressure of greater-than-or-equal-to 90 mm Hg, or the initiation of antihypertensive therapy) and for major cardiovascular events. Results. Borderline isolated systolic hypertension was the most common type of untreated hypertension among adults over the age of 60. After 20 years of follow-up, 80 percent of those with borderline isolated systolic hypertension had progression to definite hypertension, as compared with 45 percent of the normotensive participants (P<0.001). After adjustment for age, sex, and risk factors for cardiovascular disease, participants with borderline isolated systolic hypertension had an excess long-term risk of cardiovascular disease (hazard ratio, 147; 95 percent confidence interval, 1.24 to 1.74) and death from cardiovascular disease (hazard ratio, 1.57; 95 percent confidence interval, 1.24 to 2.00), as compared with normotensive participants. In an analysis of pooled data from biennial examinations to study short-term sequelae, subjects with borderline isolated systolic hypertension had an increased risk of progression to definite hypertension (odds ratio, 3.84; 95 percent confidence interval, 3.35 to 4.41) and of cardiovascular disease (odds ratio, 1.39; 95 percent confidence interval, 1.06 to 1.82). Conclusions. In both the short term and the long term, subjects with borderline isolated systolic hypertension are at increased risk of progression to definite hypertension and the development of cardiovascular disease. C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY, 5 THURBER ST, FRAMINGHAM, MA 01701 USA. NHLBI, BETHESDA, MD 20892 USA. BOSTON UNIV, SCH MED, DIV EPIDEMIOL, BOSTON, MA 02118 USA. BOSTON UNIV, SCH MED, DIV PREVENT MED, BOSTON, MA 02118 USA. BETH ISRAEL HOSP, DIV CARDIOL, BOSTON, MA 02215 USA. BETH ISRAEL HOSP, DIV CLIN EPIDEMIOL, BOSTON, MA 02215 USA. NR 33 TC 187 Z9 193 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 23 PY 1993 VL 329 IS 26 BP 1912 EP 1917 DI 10.1056/NEJM199312233292602 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA MM885 UT WOS:A1993MM88500002 PM 8247055 ER PT J AU HOOVER, DR SAAH, AJ BACELLAR, H PHAIR, J DETELS, R ANDERSON, R KASLOW, RA AF HOOVER, DR SAAH, AJ BACELLAR, H PHAIR, J DETELS, R ANDERSON, R KASLOW, RA TI CLINICAL MANIFESTATIONS OF AIDS IN THE ERA OF PNEUMOCYSTIS PROPHYLAXIS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CARINII PNEUMONIA; TRIMETHOPRIM-SULFAMETHOXAZOLE; AEROSOLIZED PENTAMIDINE; CONTROLLED TRIAL; ZIDOVUDINE; INFECTION AB Background. Among patients infected with human immunodeficiency virus type 1 (HIV-1), early and widespread use of prophylactic regimens against Pneumocystis carinii is changing the pattern of illnesses related to the acquired immunodeficiency syndrome (AIDS). Methods. We conducted a subcohort analysis of 844 men with AIDS (87 percent of whom have since died) from a prospectively followed cohort of 2592 HIV-1-infected homosexual men. Results. A total of 138 men received prophylaxis before the diagnosis of AIDS, but 39 (28 percent) nevertheless had P. carinii pneumonia at some time. Only four illnesses occurred more frequently in men who received P. carinii prophylaxis before the onset of AIDS: Mycobacterium avium complex disease, which developed in 33.4 percent, as compared with 17.3 percent of the 706 men who did not receive early prophylaxis; wasting syndrome (18.4 percent vs. 6.4 percent); cytomegalovirus disease (44.9 percent vs. 24.8 percent); and esophageal candidiasis (21.3 percent vs. 12.8 percent). Collectively, these four diseases accounted for the initial AIDS-related illness in 42.7 percent of those who received prophylaxis before the onset of AIDS, as compared with 10.7 percent of those who did not. During the three 6-month periods before the diagnosis of AIDS (0 to 6, >6 to 12, and >12 to 18 months), the geometric mean CD4+ cell counts were 48, 87, and 147 per cubic millimeter, respectively, in men who received prophylaxis against P. carinii, as compared with 118, 211, and 279 per cubic millimeter in those who did not. Conclusions. M. avium complex disease, esophageal candidiasis, wasting syndrome, and cytomegalovirus disease are more common in HIV-infected patients who have received prophylaxis against P. carinii than in those who have not. Prophylaxis may delay the first AIDS illness for 6 to 12 months. C1 NORTHWESTERN UNIV, SCH MED, DIV INFECT DIS, EVANSTON, IL 60201 USA. UNIV CALIF LOS ANGELES, SCH PUBL HLTH, LOS ANGELES, CA USA. JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, DEPT BIOSTAT, BALTIMORE, MD 21205 USA. UNIV PITTSBURGH, GRAD SCH PUBL HLTH, PITTSBURGH, PA 15260 USA. NIAID, BETHESDA, MD 20892 USA. RP HOOVER, DR (reprint author), JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, DEPT EPIDEMIOL, 624 N BROADWAY, SUITE 784, BALTIMORE, MD 21205 USA. FU NIAID NIH HHS [N01-AI-32535, N01-AI-72634, N01-AI-72676] NR 22 TC 408 Z9 413 U1 1 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 23 PY 1993 VL 329 IS 26 BP 1922 EP 1926 DI 10.1056/NEJM199312233292604 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA MM885 UT WOS:A1993MM88500004 PM 7902536 ER PT J AU PIRTLE, IL CHANG, YN LEE, MM YI, HF WANG, SY MCBRIDE, OW PIRTLE, RM AF PIRTLE, IL CHANG, YN LEE, MM YI, HF WANG, SY MCBRIDE, OW PIRTLE, RM TI A HUMAN DNA SEGMENT ENCOMPASSING LEUCINE AND METHIONINE TRANSFER-RNA PSEUDOGENES LOCALIZED OS CHROMOSOME-6 SO GENE LA English DT Article DE CHROMOSOME MAPPING; IN VITRO TRANSCRIPTION; NUCLEOTIDE SEQUENCING; RESTRICTION ENZYME MAPPING; RNA POLYMERASE III; SOMATIC CELL HYBRIDS ID TRANSFER-RNA GENE; PRE-TRANSFER RNA; NUCLEOTIDE-SEQUENCE; TRANSFER RNAIMET; VARIANT GENES; TRANSCRIPTION; ORGANIZATION; CLONING; FAMILY; ASSIGNMENT AB A human genomic clone, designated LHtlm8, that strongly hybridized to a mammalian leucine tRNA(IAG) probe, was found to encompass a pair of tRNA pseudogenes that are transcribed in a homologous cell extract. A leucine tRNA(AAG) pseudogene (TRLP1) is 2.1-kb upstream and of opposite polarity to a methionine elongator tRNA(CAU), pseudogene (TRMEP1). TRLP1 has three nucleotide variations (97% identity) from its cognate leucine tRNA(IAG), while TRMEP1 has a 78% identity with its cognate tRNA. Similar to a number of other eukaryotic tRNA pseudogenes, presumptive precursor tRNA transcripts are generated from the two pseudogenes in vitro, but possibly due to their aberrant and unstable secondary and tertiary structures, no detectable mature tRNA products are observed. The two tRNA pseudogenes are encompassed within a 9.6-kb EcoRI fragment that has been assigned to the chromosomal locus, 6pter-q13, by Southern blot hybridization of human-rodent somatic cell hybrid DNAs with probes derived from the cloned tRNA pseudogenes and flanking sequences. A 4.4-kb EcoRI fragment also harbored in clone LHtlm8 was mapped to human chromosome 11, suggesting that the two EcoRI fragments were inadvertantly ligated together during construction of the genomic library. C1 UNIV N TEXAS, DEPT BIOL SCI, DENTON, TX 76203 USA. NCI, BIOCHEM LAB, BETHESDA, MD 20892 USA. NR 48 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 EI 1879-0038 J9 GENE JI Gene PD DEC 22 PY 1993 VL 136 IS 1-2 BP 157 EP 166 DI 10.1016/0378-1119(93)90459-G PG 10 WC Genetics & Heredity SC Genetics & Heredity GA MU767 UT WOS:A1993MU76700019 PM 8293999 ER PT J AU ALLIKMETS, R GERRARD, B COURT, D DEAN, M AF ALLIKMETS, R GERRARD, B COURT, D DEAN, M TI CLONING AND ORGANIZATION OF THE ABC AND MDL GENES OF ESCHERICHIA-COLI - RELATIONSHIP TO EUKARYOTIC MULTIDRUG-RESISTANCE SO GENE LA English DT Note DE CYSTIC FIBROSIS; GLYCOPROTEINS; ATP-BINDING CASSETTE; TRANSMEMBRANE HYDROPHOBIC DOMAIN; PERMEASES ID P-GLYCOPROTEIN; CYSTIC-FIBROSIS; BACTERIAL TRANSPORT; SEQUENCE; PROTEINS; IDENTIFICATION; CHANNELS; MAP; SET AB Using degenerate oligodeoxyribonucleotides from conserved regions of the gene family encoding ATP-binding domain of the active transporter, two new Escherichia coli genes were identified. The first of the genes, named mdl (multidrug resistance-like), is located at min 10.2 of the E. coli chromosome and encodes two ATP-binding motifs and two hydro-phobic (transmembrane) domains. The ATP-binding domains of mdl show 35-38% amino acid (aa) identity with members of the eukaryotic P-glycoprotein/multidrug resistance family. To date, 25 members of the ATP-transporter/permease gene family have been characterized in E. coli. Comparison of the ATP-binding domains from this family indicates that mdl is part of a distinct subfamily of sequences that includes hlyB, msbA, and cvaB. Gene-disruption studies revealed that mdl is not essential for cell growth. The second open reading frame, named nbc (ATP-binding cassette), is located at min 4.9 of the chromosome, encodes a single ATP-binding domain, and is most homologous to ftsE, a cell division control gene of E. coli. The abe gene product also shows aa sequence homology to several E. coli permeases. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHROMOSOME BIOL LAB,FREDERICK,MD 21702. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 25 TC 41 Z9 46 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD DEC 22 PY 1993 VL 136 IS 1-2 BP 231 EP 236 DI 10.1016/0378-1119(93)90470-N PG 6 WC Genetics & Heredity SC Genetics & Heredity GA MU767 UT WOS:A1993MU76700030 PM 7904973 ER PT J AU IMAI, K NAKAMURA, M YAMADA, M ASANO, A YOKOYAMA, S TSUJI, S GINNS, EI AF IMAI, K NAKAMURA, M YAMADA, M ASANO, A YOKOYAMA, S TSUJI, S GINNS, EI TI A NOVEL TRANSCRIPT FROM A PSEUDOGENE FOR HUMAN GLUCOCEREBROSIDASE IN NON-GAUCHER DISEASE CELLS SO GENE LA English DT Note DE NUCLEOTIDE SEQUENCE; BETA-GLUCOSIDASE; CDNA; POLYMERASE CHAIN REACTION; LYSOSOMES; IN VITRO TRANSLATION ID NUCLEOTIDE-SEQUENCE; MOLECULAR-CLONING; CDNA; EXPRESSION; GENE; MUTATION AB Human glucocerebrosidase (GC)-encoding cDNA clones were isolated from a promyelocytic HL-60 cDNA library and analyzed. A novel cDNA clone was found to originate from a gene referred to as a GC pseudogene. Using the polymerase chain reaction (PCR) with primers specific for the GC pseudogene, we found that all the human cell lines examined, HL-60, K-562, WI-38, HepG2 and HeLa, expressed a pseudogene transcript. In vitro translation of RNA synthesized by transcription of the pseudogene cDNA produced a polypeptide of approximately 30 kDa. C1 OSAKA UNIV,INST PROT RES,SUITA,OSAKA 565,JAPAN. YOKOHAMA CITY UNIV,FAC LIBERAL ARTS & SCI,YOKOHAMA,KANAGAWA 236,JAPAN. SAGA UNIV,FAC AGR,SAGA 840,JAPAN. NIIGATA UNIV,BRAIN RES INST,NIIGATA 951,JAPAN. NIMH,CLIN NEUROSCI BRANCH,MOLEC NEUROGENET SECT,BETHESDA,MD 20892. RP IMAI, K (reprint author), SHIMANE MED UNIV,DEPT BIOCHEM,IZUMO,SHIMANE 693,JAPAN. NR 20 TC 7 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD DEC 22 PY 1993 VL 136 IS 1-2 BP 365 EP 368 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA MU767 UT WOS:A1993MU76700057 PM 8294033 ER PT J AU JOHNSON, KA PICKLE, LW AF JOHNSON, KA PICKLE, LW TI RISK OF BREAST-CANCER IN THE NURSES HEALTH STUDY - APPLYING THE GAIL MODEL SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NATL CTR HLTH STAT,HYATTSVILLE,MD 20782. RP JOHNSON, KA (reprint author), NCI,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 22 PY 1993 VL 270 IS 24 BP 2925 EP 2926 DI 10.1001/jama.270.24.2925 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA MM119 UT WOS:A1993MM11900013 PM 8123124 ER PT J AU NEATON, JD GRIMM, RH GRANDITS, GA FLACK, JM PRINEAS, RJ CUTLER, JA SCHOENBERGER, JA LIEBSON, PR MCDONALD, R LEWIS, CE AF NEATON, JD GRIMM, RH GRANDITS, GA FLACK, JM PRINEAS, RJ CUTLER, JA SCHOENBERGER, JA LIEBSON, PR MCDONALD, R LEWIS, CE TI THE TREATMENT OF MILD HYPERTENSION STUDY - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 UNIV MIAMI,SCH MED,MIAMI,FL 33152. NIH,BETHESDA,MD 20892. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. UNIV PITTSBURGH,SCH MED,PITTSBURGH,PA 15261. UNIV ALABAMA,BIRMINGHAM,AL 35294. RP NEATON, JD (reprint author), UNIV MINNESOTA,SCH MED,MINNEAPOLIS,MN 55455, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 22 PY 1993 VL 270 IS 24 BP 2925 EP 2925 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA MM119 UT WOS:A1993MM11900012 ER PT J AU CHAN, KC JANINI, GM MUSCHIK, GM ISSAQ, HJ AF CHAN, KC JANINI, GM MUSCHIK, GM ISSAQ, HJ TI MICELLAR ELECTROKINETIC CHROMATOGRAPHY OF HYDROXYPROLINE AND OTHER SECONDARY AMINO-ACIDS IN BIOLOGICAL SAMPLES WITH LASER-INDUCED FLUORESCENCE DETECTION SO JOURNAL OF CHROMATOGRAPHY-BIOMEDICAL APPLICATIONS LA English DT Note ID PERFORMANCE LIQUID-CHROMATOGRAPHY; 9-FLUORENYLMETHYL CHLOROFORMATE; PRECOLUMN DERIVATIZATION; COLLAGEN; PROLINE; EXCRETION; URINE; QUANTITATION; SENSITIVITY; CANCER AB Micellar electrokinetic chromatography (MEKC) with laser-induced fluorescence (LIF) was used for the rapid and sensitive detection of hydroxyproline in serum and hydrolyzed urine that were pre-column derivatized with 9-fluorenylmethyl chloroformate (FMOC). The application of the combined o-phthalaldehyde (OPA)/FMOC derivatization in MEKC for the selective detection of secondary amino acids in biological samples is investigated. RP CHAN, KC (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,POB B,FREDERICK,MD 21702, USA. NR 29 TC 25 Z9 25 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR-BIOMED JI J. Chromatogr.-Biomed. Appl. PD DEC 22 PY 1993 VL 622 IS 2 BP 269 EP 273 DI 10.1016/0378-4347(93)80276-A PG 5 WC Chemistry, Analytical SC Chemistry GA MR222 UT WOS:A1993MR22200021 PM 8150876 ER PT J AU MILEI, J SANCHEZ, J STORINO, R YU, ZX DENDUCHIS, B FERRANS, VJ AF MILEI, J SANCHEZ, J STORINO, R YU, ZX DENDUCHIS, B FERRANS, VJ TI ANTIBODIES TO LAMININ AND IMMUNOHISTOCHEMICAL LOCALIZATION OF LAMININ IN CHRONIC CHAGASIC CARDIOMYOPATHY - A REVIEW SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE LAMININ; ANTILAMININ; CHAGASIC CARDIOMYOPATHY; CHAGAS DISEASE; BASEMENT MEMBRANE; MYOCARDIAL DAMAGE ID MATRIX COMPONENTS; TRYPANOSOMA-CRUZI; RAT MYOCARDIUM; DISEASE; AUTOANTIBODIES; IMMUNOGLOBULIN; HEART; SERA AB Antibodies against laminin were determined by ELISA in forty six patients suffering from Chagas' disease and twenty healthy persons (control group). The patients were divided into three groups according to the severity of clinical, electrocardiographic and echocardiographic studies. Histologic, ultrastructural and immunohistochemical studies were made of endomyocardial biopsy specimens from 10 of these patients with chronic Chagasic cardiomyopathy. Antibodies to laminin were detected in 50% of the patients in each of the three groups. However analysis of the data did not allow us to determine any significant correlation among the severity of the different clinical and non-invasive studies and the level of circulating antibodies to laminin. The highest titers of antilaminin antibodies were detected in the group with severe cardiological alterations (37% of the patients). Histological and electron microscopic observation of myocardial biopsies disclosed marked thickening of the basement membranes of the myocytes, endothelial cells and vascular smooth muscle cells. Light (peroxidase-labeled antibodies) and electron (gold-conjugated antibody) microscopic immunohistochemical methods revealed a positive reaction for laminin in these thickened basement membranes. This thickening may develop as a consequence of: a) an immunologic reaction which is triggered by the presence of a laminin-like molecule on the surfaces of T. cruzi amastigotes and trypomastigotes; b) an immunologic response to direct injury of basement membranes causing some of their components to become antigenic; c) myocardial fibrosis, with synthesis of new connective tissue components, and d) a combination of the preceding factors. The relationship of these changes to antilaminin antibodies remains unclear. From these results, it is not possible to assure a physiopathogenic role for antibodies to laminin in chronic Chagas' cardiomyopathy. C1 UNIV BUENOS AIRES,FAC MED,CATEDRA HISTOL BUENOS AIRES,BUENOS AIRES,ARGENTINA. NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. RP MILEI, J (reprint author), HOSP JUAN A FERNANDEZ,CTR ENFERMEDAD CHAGAS & CARDIOPSIS,TUCMAN 2163 4P B,RA-1050 BUENOS AIRES,DF,ARGENTINA. OI MILEI, JOSE/0000-0003-4029-5993 NR 38 TC 14 Z9 15 U1 0 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD DEC 22 PY 1993 VL 129 IS 2 BP 161 EP 170 DI 10.1007/BF00926364 PG 10 WC Cell Biology SC Cell Biology GA MX381 UT WOS:A1993MX38100007 PM 8177238 ER PT J AU FRITSCH, M ANDERSON, I GORSKI, J AF FRITSCH, M ANDERSON, I GORSKI, J TI STRUCTURAL CHARACTERIZATION OF THE TRYPSINIZED ESTROGEN-RECEPTOR SO BIOCHEMISTRY LA English DT Article ID RAT GLUCOCORTICOID RECEPTORS; STEROID BINDING DOMAIN; LIMITED PROTEOLYSIS; TAMOXIFEN AZIRIDINE; IDENTIFICATION; ACTIVATION; ESTRADIOL; LIGAND; ANTIESTROGEN; FRAGMENT AB Structural differences between the unoccupied and ligand-occupied rat uterine estrogen receptors (ERs) were investigated using partial proteolysis followed by immunoblotting, affinity labeling, and gel filtration chromatography. Trypsin digestion of the unoccupied ER at 4-degrees-C resulted in retention of 70-80% of high-affinity [H-3]estradiol binding. Only two fragments of the rat ER were detected after prolonged trypsin treatment of the unoccupied ER followed by affinity labeling with [H-3]tamoxifen aziridine. One fragment represents the intact steroid binding domain (28 kDa), and the other fragment is about 10 kDa. The small 10-kDa fragment of the ER detected by denaturing gel electrophoresis is shown to be held in a large oligomeric complex in solution using gel filtration chromatography. This oligomeric complex probably represents the steroid binding domain, which has its tertiary structure maintained predominantly by noncovalent interactions between the trypsin-generated fragments. The estrogen, anti-estrogen, and unoccupied trypsinized ERs all result in similar patterns of fragments after separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and detection by immunoblotting. Although no new trypsin cleavage sites were exposed, the sensitivity of the available trypsin sites was altered by heating the ER and, to a lesser extent, by hormone treatment. Gel filtration chromatography of the trypsinized estradiol- and 4-hydroxytamoxifen-occupied ERs demonstrates similar, diffuse peaks centered at about the correct size for the intact steroid binding domain (28 kDa), whereas the trypsinized unoccupied ER results in a sharp, discrete peak centered at about 80 kDa. We conclude that the unoccupied steroid binding domain has a different conformation than either the estradiol- or the 4-hydroxytamoxifen-occupied steroid binding domains. C1 UNIV WISCONSIN,DEPT BIOCHEM,420 HENRY MALL,MADISON,WI 53706. NIH,BETHESDA,MD 20892. FU NICHD NIH HHS [HD08192, HD07259] NR 33 TC 16 Z9 16 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 21 PY 1993 VL 32 IS 50 BP 14000 EP 14008 DI 10.1021/bi00213a033 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MN110 UT WOS:A1993MN11000033 PM 8268178 ER PT J AU JACOBSON, KA NIKODIJEVIC, O SHI, D GALLORODRIGUEZ, C OLAH, ME STILES, GL DALY, JW AF JACOBSON, KA NIKODIJEVIC, O SHI, D GALLORODRIGUEZ, C OLAH, ME STILES, GL DALY, JW TI A ROLE FOR CENTRAL A(3)-ADENOSINE RECEPTORS - MEDIATION OF BEHAVIORAL DEPRESSANT EFFECTS SO FEBS LETTERS LA English DT Article DE ADENOSINE RECEPTOR; XANTHINE; LOCOMOTOR ACTIVITY; HISTAMINE; RADIOLIGAND BINDING ID ADENOSINE RECEPTOR; ANTAGONISTS; LOCOMOTOR; ANALOGS AB The behavioral effects of a selective A(3) adenosine receptor agonist 3-IB-MECA (N-6-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine) in mice and the localization of radioligand binding sites in mouse brain were examined. Low levels A(3) adenosine receptors were detected in various regions of the mouse brain (hippocampus, cortex, cerebellum, striatum), using a radioiodinated, high-affinity A(3)-agonist radioligand [I-125]AB-MECA (N-6-(3-iodo-4-aminobenzyl)-5'-N-methylcarboxamidoadenosine) Scatchard analysis in the cerebellum showed that the K, value for binding to A(3) receptors was 1.39 +/- 0.04 nM with a Bmax of 14.8 +/- 2.1 fmol/mg protein. 3-IB-MECA at 0.1 mg/kg i.p. was a locomotor depressant with >50% reduction in activity. Although selective A(1) or A(2), antagonists reversed locomotor depression elicited by selective A(1) or A(2a) agonists, respectively, the behavioral depressant effects of 3-IB-MECA were unaffected. 3-IB-MECA also caused scratching in mice, which was prevented by coadministration of the histamine antagonist cyproheptadine. The demonstration of a marked behavioral effect of A(3) receptor activation suggests that the A(3) receptor represents a potential new therapeutic target. C1 NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. RI Gallo-Rodriguez, Carola/E-1732-2012; Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 20 TC 113 Z9 113 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 DEC 20 PY 1993 VL 336 IS 1 BP 57 EP 60 DI 10.1016/0014-5793(93)81608-3 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA MM353 UT WOS:A1993MM35300012 PM 8262217 ER PT J AU PAINBENI, E MOURAY, E GOTTESMAN, S ROUVIEREYANIV, J AF PAINBENI, E MOURAY, E GOTTESMAN, S ROUVIEREYANIV, J TI AN IMBALANCE OF HU SYNTHESIS INDUCES MUCOIDY IN ESCHERICHIA-COLI SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE HISTONE-LIKE; CAPSULAR POLYSACCHARIDE; LON PROTEASE; SOS RESPONSE ID HISTONE-LIKE PROTEIN; CAPSULAR POLYSACCHARIDE SYNTHESIS; DNA-BINDING PROTEIN; INTEGRATION HOST FACTOR; PSEUDOMONAS-AERUGINOSA; POSITIVE REGULATOR; AUTOGENOUS CONTROL; GENE-EXPRESSION; K-12; ION C1 INST BIOL PHYSICOCHIM,PHYSIOL BACTERIENNE,13 RUE PIERRE & MARIE CURIE,F-75005 PARIS,FRANCE. NIH,DEPT HLTH & HUMAN SERV,BETHESDA,MD 20892. NR 59 TC 25 Z9 25 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD DEC 20 PY 1993 VL 234 IS 4 BP 1021 EP 1037 DI 10.1006/jmbi.1993.1656 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MN265 UT WOS:A1993MN26500013 PM 7505335 ER PT J AU CLAVERIE, JM AF CLAVERIE, JM TI DETECTING FRAME SHIFTS BY AMINO-ACID-SEQUENCE COMPARISON SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE AMINO ACID SEQUENCE; COMPUTER ANALYSIS; FRAME SHIFT; EVOLUTION; ERROR ID DEPENDENT PROTEIN-KINASE; ESCHERICHIA-COLI; SCORING MATRIX; GENE; EXPRESSION; IDENTIFICATION; CLONING; SEARCH; CYCLIN RP NIH, NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20894 USA. NR 37 TC 19 Z9 23 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD DEC 20 PY 1993 VL 234 IS 4 BP 1140 EP 1157 DI 10.1006/jmbi.1993.1666 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MN265 UT WOS:A1993MN26500023 PM 7903399 ER PT J AU TAKESHIMA, Y SEYAMA, T BENNETT, WP AKIYAMA, M TOKUOKA, S INAI, K MABUCHI, K LAND, CE HARRIS, CC AF TAKESHIMA, Y SEYAMA, T BENNETT, WP AKIYAMA, M TOKUOKA, S INAI, K MABUCHI, K LAND, CE HARRIS, CC TI P53 MUTATIONS IN LUNG CANCERS FROM NONSMOKING ATOMIC-BOMB SURVIVORS SO LANCET LA English DT Note ID GENE AB Tobacco smoke contains many carcinogens and has been linked with the development of lung cancer. We sequenced the conserved regions of the p53 tumour suppressor gene in lung cancers from 17 non-smokers from Hiroshima, Japan; 9 were atomic-bomb survivors. The mutations were predominantly transitions (all G:C to A:T); there were no G:C to T:A transversions. By contrast, lung cancers from 77 Japanese smokers have a predominance of G:C to T:A transversions in which the guanine residues occur on the non-transcribed DNA strand. These findings further implicate tobacco smoke carcinogens in the molecular pathogenesis of lung cancer. C1 NCI,BLDG 37,ROOM 2C05,BETHESDA,MD 20892. HIROSHIMA UNIV,SCH MED,HIROSHIMA 730,JAPAN. RADIAT EFFECTS RES FDN,HIROSHIMA 730,JAPAN. FU NCI NIH HHS [NCI N01-CP-71128] NR 10 TC 103 Z9 103 U1 1 U2 2 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD DEC 18 PY 1993 VL 342 IS 8886-7 BP 1520 EP 1521 DI 10.1016/S0140-6736(05)80087-X PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA MM402 UT WOS:A1993MM40200014 PM 7902903 ER PT J AU NOWAK, R AF NOWAK, R TI A MATTER OF LIFE AND DEATH SO NEW SCIENTIST LA English DT Editorial Material RP NOWAK, R (reprint author), JOURNAL NIH RES,WASHINGTON,DC, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NEW SCIENTIST PUBL EXPEDITING INC PI ELMONT PA 200 MEACHAM AVE, ELMONT, NY 11003 SN 0262-4079 J9 NEW SCI JI New Sci. PD DEC 18 PY 1993 VL 140 IS 1904 BP 12 EP 13 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MN073 UT WOS:A1993MN07300016 PM 11659700 ER PT J AU ZELAZOWSKI, P PATCHEV, VK ZELAZOWSKA, EB CHROUSOS, GP GOLD, PW STERNBERG, EM AF ZELAZOWSKI, P PATCHEV, VK ZELAZOWSKA, EB CHROUSOS, GP GOLD, PW STERNBERG, EM TI RELEASE OF HYPOTHALAMIC CORTICOTROPIN-RELEASING HORMONE AND ARGININE-VASOPRESSIN BY INTERLEUKIN-1-BETA AND ALPHA-MSH - STUDIES IN RATS WITH DIFFERENT SUSCEPTIBILITY TO INFLAMMATORY DISEASE SO BRAIN RESEARCH LA English DT Article DE CORTICOTROPIN-RELEASING HORMONE; ARGININE VASOPRESSIN; IL-1; ALPHA MELANOCYTE-STIMULATING HORMONE; ORGAN EXPLANT ID PITUITARY-ADRENAL AXIS; LEWIS RATS; ADRENOCORTICOTROPIN SECRETION; NERVOUS-SYSTEM; INVITRO; CYTOKINES; BINDING; INVIVO; SITE AB The susceptibility of Lewis rats is related to blunted hypothalamic-pituitary-adrenal (HPA) axis responsiveness to a variety of inflammatory and neurendocrine stimuli. In contrast resistance to inflammatory disease of histocompatible Fischer rats is associated with their intact HPA axis responses to the same stimuli. We have examined the contribution of IL-1 beta to in vitro corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) release from hypothalamic explants derived from LEW/N and F344/N rats. The same animal model has been used to investigate the regulatory effect of alpha MSH, an immunosuppressive neurohormone, on IL-1 beta stimulated CRH and AVP secretion. CRH basal release in bath strains was similar. However, LEW/N hypothalamic AVP basal secretion was significantly elevated. CRH relative response of LEW/N hypothalamic explants to IL-1 beta stimulation was lower compared to Fischer, which is consistent with their hyporesponsiveness to inflammatory mediators. AVP secretion however, was significantly decreased in hypothalamic explants from both strains after 40 min exposure to IL-1 beta. alpha MSH suppressed basal CRH and AVP release in both LEW/N and F344/N rats and prevented IL-1 beta stimulated CRH secretion in these strains. AVP was further diminished in F344/N explants following incubation with alpha MSH + IL-1 beta, while LEW/N level was significantly elevated. However, AVP levels remained significantly below baseline in explants from both strains after final incubation with IL-1 beta. Although our findings indicate a modulatory action of alpha MSH in HPA axis regulation in vitro, the physiological importance of this phenomenon in Lewis and Fischer rats requires further investigation. C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 24 TC 38 Z9 41 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 DEC 17 PY 1993 VL 631 IS 1 BP 22 EP 26 DI 10.1016/0006-8993(93)91181-Q PG 5 WC Neurosciences SC Neurosciences & Neurology GA MK991 UT WOS:A1993MK99100003 PM 8298992 ER PT J AU DACUNHA, A JEFFERSON, JJ TYOR, WR GLASS, JD JANNOTTA, FS VITKOVIC, L AF DACUNHA, A JEFFERSON, JJ TYOR, WR GLASS, JD JANNOTTA, FS VITKOVIC, L TI CONTROL OF ASTROCYTOSIS BY INTERLEUKIN-1 AND TRANSFORMING GROWTH-FACTOR-BETA-1 IN HUMAN BRAIN SO BRAIN RESEARCH LA English DT Article DE CYTOKINES; FRONTAL CORTEX; GLIOSIS ID HUMAN CEREBRAL-CORTEX; TUMOR-NECROSIS-FACTOR; REACTIVE GLIOSIS; FACTOR-BETA; PROLIFERATION; INJURY; RAT; EXPRESSION; INVITRO AB Astrocytosis is a common neurocellular manifestation of brain pathology in individuals with a variety of diseases. It is comprised of astrocytic hyperplasia (an increase in number of astrocytes) and astrocytic hypertrophy (an increase in size of astrocytes). The precise cause (s) of astrocytosis remains unknown. We morphometrically measured the relative extent of astrocytosis in brains of 22 individuals who died with seven different diseases. The relative amounts of interleukin-1 (IL-1) and transforming growth factor-beta 1 (TGF-beta 1) immunoreactive products (IRPs) were next assessed in sections serial to those in which astrocytosis was measured because these cytokines were shown in animal and in vitro experiments to be associated with astrocytosis. The data demonstrate that astrocytosis and these cytokines were co-localized in all examined human tissues. Relative increase in density of astrocytes was correlated with the increase in total IL-1 but not TGF-beta 1. In contrast, the increase in size of astrocytes was correlated with TGF-beta 1 associated only with astrocytes but not with total IL-1. Both IL-1 and TGF-beta 1 IRPs were present in GFAP IRP-containing and other cells, as assessed by double label immunocytochemistry. These observations suggest that IL-1 acts on astrocytes by both, paracrine and autocrine mechanisms whereas, TGF-beta 1 only acts by an autocrine mechanism. Because these correlations were statistically significant and also because a change in number and size of astrocytes constitutes the most frequent response of astrocytes to several diseases or injury, we conclude that these cytokines may mediate the most common pathological change in human brain. C1 NIAID,IMMUNOGENET LAB,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,DEPT NEUROL,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,NEUROPATHOL LAB,BALTIMORE,MD 21287. GEORGE WASHINGTON UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20037. FU PHS HHS [P0-126643] NR 37 TC 71 Z9 75 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 DEC 17 PY 1993 VL 631 IS 1 BP 39 EP 45 DI 10.1016/0006-8993(93)91183-S PG 7 WC Neurosciences SC Neurosciences & Neurology GA MK991 UT WOS:A1993MK99100005 PM 8298994 ER PT J AU KAHN, RA YUCEL, JK MALHOTRA, V AF KAHN, RA YUCEL, JK MALHOTRA, V TI ARF SIGNALING - A POTENTIAL ROLE FOR PHOSPHOLIPASE-D IN MEMBRANE TRAFFIC SO CELL LA English DT Review ID ADP-RIBOSYLATION FACTOR; GOLGI-COMPLEX; BREFELDIN-A; PROTEINS; TRANSPORT; PATHWAY C1 UNIV CALIF SAN DIEGO,DEPT BIOL,LA JOLLA,CA 92093. RP KAHN, RA (reprint author), NCI,DIV CANC TREATMENT,SAKYO KU PROGRAM,BIOL CHEM LAB,BETHESDA,MD 20892, USA. RI Malhotra, Vivek/O-9811-2014 OI Malhotra, Vivek/0000-0001-6198-7943 NR 21 TC 161 Z9 161 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD DEC 17 PY 1993 VL 75 IS 6 BP 1045 EP 1048 DI 10.1016/0092-8674(93)90314-G PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MM893 UT WOS:A1993MM89300003 PM 8261507 ER PT J AU LEACH, FS NICOLAIDES, NC PAPADOPOULOS, N LIU, B JEN, J PARSONS, R PELTOMAKI, P SISTONEN, P AALTONEN, LA NYSTROMLAHTI, M GUAN, XY ZHANG, J MELTZER, PS YU, JW KAO, FT CHEN, DJ CEROSALETTI, KM FOURNIER, REK TODD, S LEWIS, T LEACH, RJ NAYLOR, SL WEISSENBACH, J MECKLIN, JP JARVINEN, H PETERSEN, GM HAMILTON, SR GREEN, J JASS, J WATSON, P LYNCH, HT TRENT, JM DELACHAPELLE, A KINZLER, KW VOGELSTEIN, B AF LEACH, FS NICOLAIDES, NC PAPADOPOULOS, N LIU, B JEN, J PARSONS, R PELTOMAKI, P SISTONEN, P AALTONEN, LA NYSTROMLAHTI, M GUAN, XY ZHANG, J MELTZER, PS YU, JW KAO, FT CHEN, DJ CEROSALETTI, KM FOURNIER, REK TODD, S LEWIS, T LEACH, RJ NAYLOR, SL WEISSENBACH, J MECKLIN, JP JARVINEN, H PETERSEN, GM HAMILTON, SR GREEN, J JASS, J WATSON, P LYNCH, HT TRENT, JM DELACHAPELLE, A KINZLER, KW VOGELSTEIN, B TI MUTATIONS OF A MUTS HOMOLOG IN HEREDITARY NONPOLYPOSIS COLORECTAL-CANCER SO CELL LA English DT Article ID MISMATCH REPAIR; ESCHERICHIA-COLI; CHROMOSOME MICRODISSECTION; SACCHAROMYCES-CEREVISIAE; HUMAN GENOME; DNA; GENE; IDENTIFICATION; CLONING; LOCUS AB Recent studies have shown that a locus responsible for hereditary nonpolyposis colorectal cancer (HNPCC) is on chromosome 2p and that tumors developing in these patients contain alterations in microsatellite sequences (RER+ phenotype). We have used chromosome microdissection to obtain highly polymorphic markers from chromosome 2p16. These and other markers were ordered in a panel of somatic cell hybrids and used to define a 0.8 Mb interval containing the HNPCC locus. Candidate genes were then mapped, and one was found to lie within the 0.8 Mb interval. We identified this candidate by virtue of its homology to mutS mismatch repair genes. cDNA clones were obtained and the sequence used to detect germline mutations, including those producing termination codons, in HNPCC kindreds. Somatic as well as germline mutations of the gene were identified in RER+ tumor cells. This mutS homolog is therefore likely to be responsible for HNPCC. C1 UNIV HELSINKI, DEPT MED GENET, SF-00290 HELSINKI 29, FINLAND. JOHNS HOPKINS ONCOL CTR, BALTIMORE, MD 21231 USA. NATL CTR HUMAN GENOME RES, BETHESDA, MD 20892 USA. ELEANOR ROOSEVELT INST CANC RES, DENVER, CO 80206 USA. LOS ALAMOS NATL LAB, DIV LIFE SCI, LOS ALAMOS, NM 87545 USA. FRED HUTCHINSON CANC RES CTR, SEATTLE, WA 98104 USA. UNIV TEXAS, HLTH SCI CTR, SAN ANTONIO, TX 78284 USA. GENETHON, EVRY, FRANCE. INST PASTEUR, CNRS, URA 1445, UNITE GENET MOLEC HUMAINE, F-75724 PARIS 15, FRANCE. JOHNS HOPKINS UNIV, SCH PUBL HLTH & HYG, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT PATHOL, BALTIMORE, MD 21205 USA. MEM UNIV NEWFOUNDLAND, ST JOHNS A1B 3V6, NEWFOUNDLAND, CANADA. UNIV AUCKLAND, SCH MED, DEPT PATHOL, 92019 AUCKLAND, NEW ZEALAND. RI Guan, Xin-Yuan/A-3639-2009; Papadopoulos, Nickolas/K-7272-2012; Aaltonen, Lauri/A-5375-2010; OI Guan, Xin-Yuan/0000-0002-4485-6017; Aaltonen, Lauri/0000-0001-6839-4286; Peltomaki, Paivi/0000-0001-8819-2980; Nystrom, Minna/0000-0003-0827-0243 FU NCI NIH HHS [CA09320, CA35494, CA47527] NR 61 TC 1985 Z9 2013 U1 3 U2 106 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD DEC 17 PY 1993 VL 75 IS 6 BP 1215 EP 1225 DI 10.1016/0092-8674(93)90330-S PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MM893 UT WOS:A1993MM89300019 PM 8261515 ER PT J AU KUPFER, C AF KUPFER, C TI NIH - INTRAMURAL AND EXTRAMURAL PROGRAMS SO SCIENCE LA English DT Letter RP KUPFER, C (reprint author), NEI,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 17 PY 1993 VL 262 IS 5141 BP 1802 EP 1802 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MM511 UT WOS:A1993MM51100008 PM 8110279 ER PT J AU NOGUCHI, M NAKAMURA, Y RUSSELL, SM ZIEGLER, SF TSANG, M CAO, XQ LEONARD, WJ AF NOGUCHI, M NAKAMURA, Y RUSSELL, SM ZIEGLER, SF TSANG, M CAO, XQ LEONARD, WJ TI INTERLEUKIN-2 RECEPTOR GAMMA-CHAIN - A FUNCTIONAL COMPONENT OF THE INTERLEUKIN-7 RECEPTOR SO SCIENCE LA English DT Article ID CELL GROWTH-FACTOR; T-CELLS; SIGNAL TRANSDUCTION; FETAL THYMOCYTES; SUPERFAMILY; EXPRESSION; CLONING; SUBUNIT; GP130 AB The interleukin-2 receptor gamma chain (IL-2Rgamma) is a necessary component of functional IL-2 receptors. IL-2Rgamma mutations result in X-linked severe combined immunodeficiency (XSCID) in humans, a disease characterized by the presence of few or no T cells. In contrast, SCID patients with IL-2 deficiency and IL-2-deficient mice have normal numbers of T cells, suggesting that IL-2Rgamma is part of more than one cytokine receptor. By using chemical cross-linking, IL-2Rgamma was shown to be physically associated with the IL-7 receptor. The presence of IL-2Rgamma augmented both IL-7 binding affinity and the efficiency of internalization of IL-7. These findings may help explain the defects of XSCID. Given its role in more than one cytokine receptor system, the common gamma chain (gamma(c) is proposed as the designation for IL-2Rgamma. C1 NHLBI,PULM & MOLEC IMMUNOL SECT,BETHESDA,MD 20892. IMMUNEX CORP,SEATTLE,WA 98101. RI Russell, Sarah/B-9341-2009 OI Russell, Sarah/0000-0001-5826-9641 NR 36 TC 760 Z9 764 U1 3 U2 14 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 17 PY 1993 VL 262 IS 5141 BP 1877 EP 1880 DI 10.1126/science.8266077 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MM511 UT WOS:A1993MM51100037 PM 8266077 ER PT J AU RUSSELL, SM KEEGAN, AD HARADA, N NAKAMURA, Y NOGUCHI, M LELAND, P FRIEDMANN, MC MIYAJIMA, A PURI, RK PAUL, WE LEONARD, WJ AF RUSSELL, SM KEEGAN, AD HARADA, N NAKAMURA, Y NOGUCHI, M LELAND, P FRIEDMANN, MC MIYAJIMA, A PURI, RK PAUL, WE LEONARD, WJ TI INTERLEUKIN-2 RECEPTOR GAMMA-CHAIN - A FUNCTIONAL COMPONENT OF THE INTERLEUKIN-4 RECEPTOR SO SCIENCE LA English DT Article ID GROWTH SIGNAL TRANSDUCTION; HUMAN IL-2 RECEPTOR; T-CELL LINE; BETA-CHAIN; LIGAND-BINDING; GM-CSF; SUBUNIT; PROLIFERATION; EXPRESSION; CLONING AB The interleukin-2 (IL-2) receptor gamma chain (IL-2Rgamma) is an essential component of high- and intermediate-affinity IL-2 receptors. IL-2Rgamma was demonstrated to be a component of the IL-4 receptor on the basis of chemical cross-linking data, the ability of IL-2Rgamma to augment IL-4 binding affinity, and the requirement for IL-2Rgamma in IL-4-mediated phosphorylation of insulin receptor substrate-1. The observation that IL-2Rgamma is a functional component of the IL-4 receptor, together with the finding that IL-2Rgamma associates with the IL-7 receptor, begins to elucidate why deficiency of this common gamma chain (gamma(c)) has a profound effect on lymphoid function and development, as seen in X-linked severe combined immunodeficiency. C1 NHLBI,PULM & MOLEC IMMUNOL SECT,BETHESDA,MD 20892. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. DNAX RES INST MOLEC & CELLULAR BIOL INC,PALO ALTO,CA 94304. US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,BETHESDA,MD 20892. RI Russell, Sarah/B-9341-2009 OI Russell, Sarah/0000-0001-5826-9641 NR 51 TC 767 Z9 774 U1 3 U2 12 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 17 PY 1993 VL 262 IS 5141 BP 1880 EP 1883 DI 10.1126/science.8266078 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MM511 UT WOS:A1993MM51100038 PM 8266078 ER PT J AU LEVYTOLEDANO, R ACCILI, D TAYLOR, SI AF LEVYTOLEDANO, R ACCILI, D TAYLOR, SI TI DELETION OF C-TERMINAL 113 AMINO-ACIDS IMPAIRS PROCESSING AND INTERNALIZATION OF HUMAN INSULIN-RECEPTOR - COMPARISON OF RECEPTORS EXPRESSED IN CHO AND NIH-3T3 CELLS SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE INSULIN; INSULIN RECEPTOR; TYROSINE KINASE; PHOSPHORYLATION; MITOGENESIS ID TYROSINE KINASE-ACTIVITY; AUTOPHOSPHORYLATION; BINDING; PHOSPHORYLATION; RESIDUES; PROTEIN; REPLACEMENT; TRUNCATION; LACKING; FAMILY AB We have studied the structure and the function of a truncated human insulin receptor in which 113 amino acids (aa 1231-1343) at the C-terminus of the beta-subunit were deleted. In this study, wild-type and truncated insulin receptors were expressed by stable transfection in NIH-3T3 cells and CHO cells. The mutation impairs post-translational processing of the insulin receptor; proteolytic cleavage is retarded, and degradation of the truncated receptor is accelerated. Furthermore, insulin-stimulated autophosphorylation of the mutant insulin receptor is impaired. This is associated with a defect in insulin-stimulated endocytosis. Finally, in NIH-3T3 cells, the mutant insulin receptor failed to mediate the mitogenic effects of insulin. In CHO cells, transfection of insulin receptor cDNA (either wild-type or mutant) did not alter mitogenic response to insulin. It has previously been shown that deletion of 43 amino acids at the C-terminus of the beta-subunit did not affect insulin receptor tyrosine kinase activity. Our data suggest that the structural domain located 43-113 amino acids from the C-terminus appears to have several functional roles. First, the domain appears to promote folding of receptor into the optimal conformation for post-translational processing. Second, the presence of this domain appears to promote the stability of the receptor beta-subunit in intact cells. Finally, perhaps as a consequence of the effects upon the stability of the receptor, this domain is required in intact cells for insulin-stimulated autophosphorylation and signal transmission. C1 NIDDKD,DIABET BRANCH,BLDG 10,ROOM 85-239,BETHESDA,MD 20892. NR 41 TC 16 Z9 16 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 DEC 16 PY 1993 VL 1220 IS 1 BP 1 EP 14 DI 10.1016/0167-4889(93)90090-C PG 14 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MP368 UT WOS:A1993MP36800001 PM 8268238 ER PT J AU SHIMIZU, Y SHAW, S AF SHIMIZU, Y SHAW, S TI CELL-ADHESION - MUCINS IN THE MAINSTREAM SO NATURE LA English DT Editorial Material C1 NCI, EXPTL IMMUNOL BRANCH, BETHESDA, MD 20892 USA. RP SHIMIZU, Y (reprint author), UNIV MICHIGAN, SCH MED, DEPT MICROBIOL & IMMUNOL, ANN ARBOR, MI 48109 USA. OI Shimizu, Yoji/0000-0001-9760-0288 NR 13 TC 179 Z9 180 U1 1 U2 3 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD DEC 16 PY 1993 VL 366 IS 6456 BP 630 EP 631 DI 10.1038/366630a0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MM265 UT WOS:A1993MM26500044 PM 7505052 ER PT J AU BOGUSKI, MS MCCORMICK, F AF BOGUSKI, MS MCCORMICK, F TI PROTEINS REGULATING RAS AND ITS RELATIVES SO NATURE LA English DT Review ID GTP-BINDING PROTEIN; ADP-RIBOSYLATION FACTOR; GUANINE-NUCLEOTIDE EXCHANGE; RECEPTOR TYROSINE KINASES; CELL-CYCLE GENE; SACCHAROMYCES-CEREVISIAE; MOLECULAR-CLONING; ACTIVATING PROTEIN; CDC25 GENE; GERANYLGERANYL TRANSFERASE AB GTPases of the Ras superfamily regulate many aspects of cell growth, differentiation and action. Their functions depend on their ability to alternate between inactive and active forms, and on their cellular localization. Numerous proteins affecting the GTPase activity, nucleotide exchange rates and membrane localization of Ras superfamily members have now been identified. Many of these proteins are much larger and more complex than their targets, containing multiple domains capable of interacting with an intricate network of cellular enzymes and structures. C1 ONOX PHARMACEUT,RICHMOND,CA 94806. RP BOGUSKI, MS (reprint author), NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894, USA. NR 127 TC 1702 Z9 1716 U1 9 U2 66 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD DEC 16 PY 1993 VL 366 IS 6456 BP 643 EP 654 DI 10.1038/366643a0 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MM265 UT WOS:A1993MM26500059 PM 8259209 ER PT J AU HATCH, EE BRACKEN, MB AF HATCH, EE BRACKEN, MB TI ASSOCIATION OF DELAYED CONCEPTION WITH CAFFEINE CONSUMPTION SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE CAFFEINE; FERTILITY; INFERTILITY ID DECREASED FERTILITY; CIGARETTE-SMOKING; SPERM MOTILITY; BEVERAGES; COFFEE; WOMEN; PREGNANCY; EXPOSURE; DRINKING; MICE AB This cross-sectional study investigated the relation between intake of caffeine-containing beverages and time to conception in a population of 1,909 married women in New Haven, Connecticut, between May 12, 1980 and March 12, 1982. Women were interviewed shortly after the first prenatal visit regarding the length of time taken to conceive the index pregnancy, consumption of caffeine during pregnancy, and other exposures occurring prior to and during pregnancy. In logistic regression analyses, intake of caffeine from coffee, tea, and caffeinated soft drinks was associated with an increased risk of a delay of conception of 1 year or more. Compared with no caffeine use, consumption of 1-150 mg/day of caffeine resulted in an odds ratio for delayed conception of 1.39 (95% confidence interval (Cl) 0.90-2.13), consumption of 151-300 mg/day of caffeine was associated with an odds ratio of 1.88 (95% Cl 1.13-3.11), and that of over 300 mg/day (the equivalent of approximately three cups of coffee) resulted in an odds ratio of 2.24 (95% Cl 1.06-4.73), after controlling for last method of birth control used, parity, and number of cigarettes per day. When the risk of conception for each cycle was examined using a discrete analogue of the Cox proportional hazards model, women who reported drinking over 300 mg/day of caffeine had a 27% lower chance of conceiving for each cycle, and those who reported drinking less than 300 mg/day had a 10% reduction in per cycle conception rates compared with women who consumed no caffeine. Risks for coffee, tea, and colas were examined simultaneously in logistic models and were found not to improve the fit of a model that contained a variable for total caffeine intake from all sources. C1 YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT 06510. RP HATCH, EE (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EPN 408,6130 EXECUT BLVD,ROCKVILLE,MD 20852, USA. FU NCI NIH HHS [5.T32.CA09279-09]; NICHD NIH HHS [HD11357]; NIDA NIH HHS [DA05484] NR 39 TC 52 Z9 52 U1 1 U2 6 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 15 PY 1993 VL 138 IS 12 BP 1082 EP 1092 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA MP873 UT WOS:A1993MP87300006 PM 8266910 ER PT J AU GEJMAN, PV GELERNTER, J AF GEJMAN, PV GELERNTER, J TI MUTATIONAL ANALYSIS OF CANDIDATE GENES IN PSYCHIATRIC-DISORDERS SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE DENATURING GRADIENT GEL ELECTROPHORESIS; SINGLE STRANDED CONFORMATIONAL POLYMORPHISMS; CHEMICAL CLEAVAGE; ASSOCIATION ID GRADIENT GEL-ELECTROPHORESIS; POLYMERASE-CHAIN-REACTION; SINGLE BASE SUBSTITUTIONS; DNA FRAGMENTS; NUCLEAR EXTRACTS; POINT MUTATIONS; G.T MISPAIRS; GENOMIC DNA; HUMAN-CELLS; GC-CLAMP AB A genetic hypothesis for a disease presupposes the existence of variation in the DNA sequences of affected individuals. A series of techniques known together as ''mutational analysis'' can be applied towards identifying new sequence variations in selected genes. These techniques can screen a large series of individuals for mutations efficiently, so it is not necessary to determine the nucleotide sequence in every DNA sample. DNA samples suspected of harboring sequence variants are then sequenced. Denaturing gradient gel electrophoresis techniques, single stranded conformation polymorphism paradigms, and chemical cleavage of mismatches are 3 procedures widely used for the molecular screening of mutations today. We discuss each of these techniques for mutation screening. (C) 1993 Wiley-Liss, Inc. C1 YALE UNIV,SCH MED,W HAVEN VET ADM MED CTR,DEPT PSYCHIAT,DIV MOLEC PSYCHIAT,W HAVEN,CT 06516. RP GEJMAN, PV (reprint author), NIMH,CLIN NEUROGENET BRANCH,10-3N218,BETHESDA,MD 20892, USA. FU NIMH NIH HHS [NIMH SDA-C MH00931] NR 60 TC 11 Z9 11 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD DEC 15 PY 1993 VL 48 IS 4 BP 184 EP 191 DI 10.1002/ajmg.1320480404 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA ML602 UT WOS:A1993ML60200003 PM 8135301 ER PT J AU FERRIS, FL FREIDLIN, V KASSOFF, A GREEN, SB MILTON, RC AF FERRIS, FL FREIDLIN, V KASSOFF, A GREEN, SB MILTON, RC TI RELATIVE LETTER AND POSITION DIFFICULTY ON VISUAL-ACUITY CHARTS FROM THE EARLY-TREATMENT-DIABETIC-RETINOPATHY-STUDY SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB Ten Sloan letters were used in the visual acuity charts developed for use in the Early Treatment Diabetic Retinopathy Study. We used the data from the 3,710 Early Treatment Diabetic Retinopathy Study subjects to investigate the relative difficulty of the ten Sloan letters and to evaluate whether the position of a letter on a line affected its relative difficulty. In general, our findings were consistent with those of the previous study. The four letters with curved contours (C, O, S, and D) were more difficult to discern at threshold than the six letters (Z, N, H, V, R, and K) composed of straight lines. Our data demonstrate that under these test conditions, letters at the end of a line are more likely to be read incorrectly than letters at the beginning of the line. This finding indicates that these data are probably not useful for evaluating possible crowding phenomena. C1 ALBANY MED COLL,DEPT OPHTHALMOL,ALBANY,NY. NCI,CLIN & DIAGNOST TRIALS SECT,BETHESDA,MD. RP FERRIS, FL (reprint author), NEI,BIOMETRY & EPIDEMIOL PROGRAM,BLDG 31,ROOM 6A24,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 6 TC 28 Z9 28 U1 0 U2 1 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 DEC 15 PY 1993 VL 116 IS 6 BP 735 EP 740 PG 6 WC Ophthalmology SC Ophthalmology GA MK478 UT WOS:A1993MK47800010 PM 8250077 ER PT J AU BOUMPAS, DT CHROUSOS, GP WILDER, RL CUPPS, TR BALOW, JE AF BOUMPAS, DT CHROUSOS, GP WILDER, RL CUPPS, TR BALOW, JE TI GLUCOCORTICOID THERAPY FOR IMMUNE-MEDIATED DISEASES - BASIC AND CLINICAL CORRELATES SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID RHEUMATOID-ARTHRITIS; INDUCED OSTEOPOROSIS; PULSE METHYLPREDNISOLONE; HUMAN-LYMPHOCYTES; NEGATIVE REGULATION; GENE-TRANSCRIPTION; ENDOTHELIAL-CELLS; MESSENGER-RNA; DNA-BINDING; C-JUN AB Glucocorticoids are pleiotropic hormones that at pharmacologic doses prevent or suppress inflammation and other immunologically mediated processes. At the molecular level, glucocorticoids form complexes with specific receptors that migrate to the nucleus where they interact with selective regulatory sites within DNA; this results in positive and negative modulation of several genes involved in inflammatory and immune responses. At the cellular level, glucocorticoids inhibit the access of leukocytes to inflammatory sites; interfere with the functions of leukocytes, endothelial cells, and fibroblasts; and suppress the production and the effects of humoral factors involved in the inflammatory response. Clinically, several modes of glucocorticoid administration are used, depending on the disease process, the organ involved, and the extent of involvement. High doses of daily glucocorticoids are usually required in patients with severe diseases involving major organs, whereas alternate-day regimens may be used in patients with less aggressive diseases. Intravenous glucocorticoids (pulse therapy) are frequently used to initiate therapy in patients with rapidly progressive, immunologically mediated diseases. The benefits of glucocorticoid therapy can easily be offset by severe side effects; even with the greatest care, side effects may occur. Moreover, for certain complications (for example, infection diathesis, peptic ulcer, osteoporosis, avascular necrosis, and atherosclerosis), other drug toxicities and pathogenic factors overlap with glucocorticoid effects. Minimizing the incidence and severity of glucocorticoid-related side effects requires carefully decreasing the dose; using adjunctive disease-modifying immunosuppressive and anti-inflammatory agents; and taking general preventive measures. RP BOUMPAS, DT (reprint author), NIDDKD,KIDNEY DIS SECT,BLDG 10,ROOM 3N-112,BETHESDA,MD 20892, USA. NR 97 TC 480 Z9 498 U1 1 U2 12 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 15 PY 1993 VL 119 IS 12 BP 1198 EP 1208 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA MM121 UT WOS:A1993MM12100007 PM 8239251 ER PT J AU DOMANSKI, MJ BUXTON, AE AF DOMANSKI, MJ BUXTON, AE TI THE PRIMARY PREVENTION OF SUDDEN-DEATH IN PATIENTS WITH CORONARY-ARTERY DISEASE SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID HOSPITAL VENTRICULAR-FIBRILLATION; SIGNAL-AVERAGED ELECTROCARDIOGRAM; CARDIAC-ARREST; MYOCARDIAL-INFARCTION; ARRHYTHMIC EVENTS; DEFIBRILLATOR; SURVIVORS; DYSFUNCTION; PREDICTION C1 TEMPLE UNIV,HLTH SCI CTR,SCH MED,PHILADELPHIA,PA 19140. RP DOMANSKI, MJ (reprint author), NHLBI,CLIN TRIALS BRANCH,BETHESDA,MD 20892, USA. NR 20 TC 1 Z9 1 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 15 PY 1993 VL 119 IS 12 BP 1218 EP 1220 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA MM121 UT WOS:A1993MM12100011 PM 8239255 ER PT J AU STEINERT, PM YANG, JM BALE, SJ COMPTON, JG AF STEINERT, PM YANG, JM BALE, SJ COMPTON, JG TI CONCURRENCE BETWEEN THE MOLECULAR OVERLAP REGIONS IN KERATIN INTERMEDIATE FILAMENTS AND THE LOCATIONS OF KERATIN MUTATIONS IN GENODERMATOSES SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID EPIDERMOLYSIS-BULLOSA SIMPLEX; GENETIC-BASIS; COILED-COIL; HYPERKERATOSIS; PEPTIDE; DOMAINS; END RP STEINERT, PM (reprint author), NIAMSD,SKIN BIOL BRANCH,BLDG 6,ROOM 425,BETHESDA,MD 20892, USA. NR 35 TC 80 Z9 82 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 15 PY 1993 VL 197 IS 2 BP 840 EP 848 DI 10.1006/bbrc.1993.2555 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MM436 UT WOS:A1993MM43600070 PM 7505575 ER PT J AU TASAKI, I BYRNE, PM AF TASAKI, I BYRNE, PM TI RAPID HEAT-PRODUCTION ASSOCIATED WITH EXCITATION OF ELECTRIC ORGANS OF THE ELECTRIC-EEL SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID NERVE RP TASAKI, I (reprint author), NIMH,CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 9 TC 8 Z9 8 U1 1 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 15 PY 1993 VL 197 IS 2 BP 910 EP 915 DI 10.1006/bbrc.1993.2565 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MM436 UT WOS:A1993MM43600080 PM 8267630 ER PT J AU WOLOZIN, B LESCH, P LEBOVICS, R SUNDERLAND, T AF WOLOZIN, B LESCH, P LEBOVICS, R SUNDERLAND, T TI OLFACTORY NEUROBLASTS FROM ALZHEIMER DONORS - STUDIES ON APP PROCESSING AND CELL REGULATION SO BIOLOGICAL PSYCHIATRY LA English DT Article DE AMYLOID; NGF; CAMP; LYSOSOME; ELECTROPHORESIS ID AMYLOID PRECURSOR PROTEIN; NERVE GROWTH-FACTOR; BETA-PROTEIN; MESSENGER-RNA; DIFFERENTIAL EXPRESSION; HUMAN BRAIN; DISEASE; IDENTIFICATION; PEPTIDE; GENE AB Cell lines of continuously dividing human olfactory neuroblasts can be propagated using olfactory epithelium obtained from human donors at biopsy or autopsy. The expression of neuronal proteins in these cells, such as neurofilament protein and tau protein, can be increased using a combination of factors including nerve growth factor, fibroblast growth factor, interleukin 1 and interleukin 6 These cells also express aspects of human disease. Olfactory neuroblasts generated from donors with the common, sporadic forms of Alzheimer's disease, show elevated levels of the direct precursor to beta-amyloid, the amyloid precursor protein C-terminal derivative (CTD). When treated with the lysosomal inhibitor chloroquine, immunoblots of Alzheimer olfactory neuroblasts show seven-fold higher levels of CTDs than immunoblots from age-matched control neuroblasts. The disease related increases in CTDs can be reversed by treatment with agents that increase intracellular cyclic adenosine monophosphate (cAMP), such as dibutyril-cyclic-AMP, theophylline, and isoproteronol. C1 NIDCD,DEPT OTOLARYNGOL,BETHESDA,MD. UNIV WURZBURG,DEPT PSYCHIAT,WURZBURG,GERMANY. RP WOLOZIN, B (reprint author), NIMH,LCS,GERIATR PSYCHIAT SECT,BLDG 10,ROOM 3041,9080 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Wolozin, Benjamin/0000-0003-2068-1475 NR 44 TC 37 Z9 38 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 DEC 15 PY 1993 VL 34 IS 12 BP 824 EP 838 DI 10.1016/0006-3223(93)90051-E PG 15 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA MN118 UT WOS:A1993MN11800002 PM 8110910 ER PT J AU BARTLEY, AJ JONES, DW TORREY, EF ZIGUN, JR WEINBERGER, DR AF BARTLEY, AJ JONES, DW TORREY, EF ZIGUN, JR WEINBERGER, DR TI SYLVIAN FISSURE ASYMMETRIES IN MONOZYGOTIC TWINS - A TEST OF LATERALITY IN SCHIZOPHRENIA SO BIOLOGICAL PSYCHIATRY LA English DT Article DE SYLVIAN FISSURE; LATERALITY; MAGNETIC RESONANCE IMAGING; MONOZYGOTIC TWINS; GENETICS ID REVERSED CEREBRAL ASYMMETRY; MAGNETIC-RESONANCE; HEMISPHERIC ASYMMETRIES; DEVELOPMENTAL DYSLEXIA; TOMOGRAPHIC SCANS; PLANUM TEMPORALE; HUMAN-BRAIN; ABNORMALITIES; DISORDER; DISCORDANT AB To address prior reports that schizophrenia is associated with loss of normal brain asymmetry and that it might be linked to a defect of a gene controlling cerebral lateralization, we measured on three-dimensional cortical renderings from magnetic resonance imaging (MRI) scans the lengths and angles of the sylvian fissures in 10 normal monozygotic (MZ) twin pairs (n=10 pairs) and in 10 MZ pairs discordant for schizophrenia (n=10 pairs). We confirmed in both sets of twins the expected normal asymmetries of length and angle of the sylvian fissure. We also confirmed that the length asymmetry occurs solely in the region of the planum temporale. In the discordant twins, affected and unaffected twins did not differ in asymmetry measures, thus failing to support an association between illness per se and diminished asymmetry. Moreover, the discordant twins as a group did not differ from the normal twins as a group, thus failing to confirm the hypothesis of a genetic association with abnormal asymmetry. The implications of variations in methodology and patient samples are discussed. C1 NIMH,NEUROSCI CTR ST ELIZABETHS,INTRAMURAL RES PROGRAM,WASHINGTON,DC 20032. NR 53 TC 53 Z9 55 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 1993 VL 34 IS 12 BP 853 EP 863 DI 10.1016/0006-3223(93)90053-G PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA MN118 UT WOS:A1993MN11800004 PM 8110912 ER PT J AU KENNEY, RT MALECH, HL EPSTEIN, ND ROBERTS, RL LETO, TL AF KENNEY, RT MALECH, HL EPSTEIN, ND ROBERTS, RL LETO, TL TI CHARACTERIZATION OF THE P67(PHOX) GENE - GENOMIC ORGANIZATION AND RESTRICTION-FRAGMENT-LENGTH-POLYMORPHISM ANALYSIS FOR PRENATAL-DIAGNOSIS IN CHRONIC GRANULOMATOUS-DISEASE SO BLOOD LA English DT Article ID NADPH OXIDASE; CHROMOSOMAL LOCATION; MUTATIONS; CHAIN; CLONING; RFLP; POLYMERASE; DELETION; P22-PHOX; VECTORS C1 UNIV CALIF LOS ANGELES, MED SCH, DEPT PEDIAT, LOS ANGELES, CA USA. NHLBI, CLIN HEMATOL BRANCH, BETHESDA, MD 20892 USA. RP KENNEY, RT (reprint author), NIAID, HOST DEF LAB, BLDG 4, RM 126, BETHESDA, MD 20892 USA. NR 34 TC 32 Z9 35 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 1993 VL 82 IS 12 BP 3739 EP 3744 PG 6 WC Hematology SC Hematology GA MM263 UT WOS:A1993MM26300030 PM 7903171 ER PT J AU MITCHELL, JB WINK, DA DEGRAFF, W GAMSON, J KEEFER, LK KRISHNA, MC AF MITCHELL, JB WINK, DA DEGRAFF, W GAMSON, J KEEFER, LK KRISHNA, MC TI HYPOXIC MAMMALIAN-CELL RADIOSENSITIZATION BY NITRIC-OXIDE SO CANCER RESEARCH LA English DT Note ID OXYGEN ENHANCEMENT RATIO; NO AB The bioregulatory molecule, nitric oxide (NO), was evaluated as a hypoxic cell radiosensitizer. Authentic NO gas was nearly as effective as oxygen in radiosensitizing hypoxic Chinese hamster V79 lung cells as evaluated using clonogenic assays. When NO was delivered to hypoxic Chinese hamster V79 cells using the NO-releasing agent (C2H2)2N[N(O)NO]-Na+, radiosensitization was also observed with a sensitizer enhancement ratio of 2.4 (1 mM (C2H5)2N[N(O)NO]-Na+). Aerobic radiosensitivity was not affected at this concentration. The hypoxic cell radiosensitization properties of (C2H5)2N[N(O)NO]-Na+, coupled with the vasodilatory effects of NO on tumor vasculature, suggest that such agents open a new avenue of research in radiation oncology. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RP MITCHELL, JB (reprint author), NCI,RADIAT ONCOL BRANCH,RADIAT BIOL SECT,BLDG 10,ROOM B3-B69,BETHESDA,MD 20892, USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 17 TC 155 Z9 158 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1993 VL 53 IS 24 BP 5845 EP 5848 PG 4 WC Oncology SC Oncology GA ML589 UT WOS:A1993ML58900002 PM 8261391 ER PT J AU PHANG, JM POORE, CM LOPACZYNSKA, J YEH, GC AF PHANG, JM POORE, CM LOPACZYNSKA, J YEH, GC TI FLAVONOL-STIMULATED EFFLUX OF 7,12-DIMETHYLBENZ(A)ANTHRACENE IN MULTIDRUG-RESISTANT BREAST-CANCER CELLS SO CANCER RESEARCH LA English DT Article ID P-GLYCOPROTEIN; BENZO(A)PYRENE; CARCINOGENS; TRANSPORT; AGENTS; MICE AB We used a series of P-glycoprotein (P-gp) expressing multidrug-resistant (MDR) cells, developed from human breast cancer MCF-7 cells by exposure to Adriamycin, to investigate the effects of flavonoids on P-gp-mediated efflux mechanisms for chemical carcinogens. We previously showed that MDR cells derived from exposure to Adriamycin are cross-resistant to a chemical carcinogen, benzo(a)pyrene, due to its cellular efflux by the P-gp-mediated putative drug efflux pump. Our current studies extended this observation to another polycyclic aromatic hydrocarbon, 7,12-dimethylbenz(a)anthracene, known to induce mammary tumors in animals. In our attempt to find naturally occurring dietary compounds which may stimulate the P-gp-mediated efflux of carcinogens, we found that certain flavonols, kaempferol, quercetin, and galangin, are potent stimulators of the P-gp-mediated efflux of 7,12-dimethylbenz(a)-anthracene. The increased efflux decreased the cellular burden of 7,12-dimethylbenz(a)anthracene. Since these flavonol compounds are widely distributed in fruits and vegetables, their stimulatory effect on P-gp may be a mechanism relevant to carcinogenesis and the observed lowered cancer risk in humans with higher dietary intake of fruits and vegetables. RP PHANG, JM (reprint author), NCI,FCRDC,DIV CANC PREVENT & CONTROL,NUTR & MOLEC REGULAT LAB,BLDG 560,RM 12-48,FREDERICK,MD 21702, USA. NR 25 TC 106 Z9 107 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1993 VL 53 IS 24 BP 5977 EP 5981 PG 5 WC Oncology SC Oncology GA ML589 UT WOS:A1993ML58900026 PM 7903198 ER PT J AU FELSENFELD, G AF FELSENFELD, G TI CHROMATIN STRUCTURE AND THE EXPRESSION OF GLOBIN-ENCODING GENES SO GENE LA English DT Article; Proceedings Paper CT COGENE Symposium - From the Double Helix to the Human Genome: 40 Years of Molecular Genetics CY APR 21-23, 1993 CL UNESCO HEADQUARTERS, PARIS, FRANCE SP INT COUNCIL SCI UNION, COMM GENET EXPERIMENTAT HO UNESCO HEADQUARTERS DE TRANSCRIPTION; TRANS-ACTING FACTORS; GATA-1; LOCUS CONTROL REGION; CHROMATIN DOMAIN; NUCLEOSOME; SUPERCOILING ID ERYTHROID TRANSCRIPTION FACTOR; DNA-BINDING PROTEIN; DEVELOPMENTAL REGULATION; NUCLEOSOME CORE; TRANSGENIC MICE; FACTOR GATA-1; 5' END; ENHANCER; SEQUENCE; REGION AB The developmental regulation of globin gene expression in the chicken has been studied. All of the genes are regulated by a small number of general erythroid factors. In addition, expression of individual members of the family must be controlled in a lineage (stage)-specific manner. In some cases, the relevant factors may be stage specific, but in others they are not confined to one stage, but exert their control through developmentally regulated changes in their abundance within the nucleus. Chromatin structural elements, such as locus control regions and insulators, are also involved in control of eukaryotic gene expression. Because so much is understood about regulation of individual genes, the globin family has proven valuable in investigating control of transcription at the level of chromatin structure. RP FELSENFELD, G (reprint author), NIDDKD,MOLEC BIOL LAB,BLDG 5,ROOM 212,BETHESDA,MD 20892, USA. NR 41 TC 33 Z9 34 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD DEC 15 PY 1993 VL 135 IS 1-2 BP 119 EP 124 DI 10.1016/0378-1119(93)90056-9 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA MQ348 UT WOS:A1993MQ34800018 PM 8276248 ER PT J AU SINGER, MF KREK, V MCMILLAN, JP SWERGOLD, GD THAYER, RE AF SINGER, MF KREK, V MCMILLAN, JP SWERGOLD, GD THAYER, RE TI LINE-1 - A HUMAN TRANSPOSABLE ELEMENT SO GENE LA English DT Article; Proceedings Paper CT COGENE Symposium - From the Double Helix to the Human Genome: 40 Years of Molecular Genetics CY APR 21-23, 1993 CL UNESCO HEADQUARTERS, PARIS, FRANCE SP INT COUNCIL SCI UNION, COMM GENET EXPERIMENTAT HO UNESCO HEADQUARTERS DE RETROTRANSPOSITION; NON-LTR-RETROTRANSPOSON; LEUCINE ZIPPER; TRANSCRIPTION; REVERSE TRANSCRIPTASE; TERATOCARCINOMA CELLS ID EMBRYONAL CARCINOMA-CELLS; DNA-SEQUENCES; TRANSCRIPTION FACTOR; TRANSLATION; PROTEIN; FAMILY; GENE; RETROTRANSPOSONS; MECHANISM; INSERTION AB Among the 10(5) LINE-1 sequences (L1Hs) in the human genome are one or more 6-kb segments that are active retrotransposons. Expression of these retrotransposons appears to be favored in cells of germ line origin, as well as in some other tumor cells of epithelial origin. In such cells, the product of the first L1Hs open reading frame (ORF), a protein called p40, is detectable; p40 has no apparent similarity to gag proteins, but contains a leucine zipper region which may be responsible for the occurrence of p40 multimers. Transcription of L1Hs initiates at residue 1 although the transcriptional regulatory regions are downstream in the first 670 bp of the 5' untranslated region; deletion of a YY1-binding site in the first 20 bp reduces transcription by fivefold. Translation of the second ORF, which encodes reverse transcriptase, is independent of the translation of the frame encoding p40. RP SINGER, MF (reprint author), NCI,BIOCHEM LAB,BLDG 37,ROOM 4A-01,BETHESDA,MD 20892, USA. NR 28 TC 39 Z9 42 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD DEC 15 PY 1993 VL 135 IS 1-2 BP 183 EP 188 DI 10.1016/0378-1119(93)90064-A PG 6 WC Genetics & Heredity SC Genetics & Heredity GA MQ348 UT WOS:A1993MQ34800026 PM 8276257 ER PT J AU FRADKIN, JE MILLS, JL SCHONBERGER, LB WYSOWSKI, DK THOMSON, R DURAKO, SJ ROBISON, LL AF FRADKIN, JE MILLS, JL SCHONBERGER, LB WYSOWSKI, DK THOMSON, R DURAKO, SJ ROBISON, LL TI RISK OF LEUKEMIA AFTER TREATMENT WITH PITUITARY GROWTH-HORMONE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID UNITED-STATES; MEDULLOBLASTOMA; EPIDEMIOLOGY; CHILDREN; HISTORY AB Objective.-To determine whether pituitary-derived human growth hormone treatment increases the subsequent risk of developing leukemia and lymphoma. Design.-Cohort study. Setting.-United States. Participants.-A total of 6284 recipients of pituitary-derived human growth hormone distributed by the National Hormone and Pituitary Program between 1963 and 1985. Main Outcome Measures.-Leukemia and lymphoma. Results.-Three cases of leukemia occurred in 59736 patient-years of follow-up from the start of growth hormone therapy to case ascertainment at interview; this number was not significantly higher (P=.23) than the 1.66 cases expected in the US age-, race-, and gender-matched general population. Three additional cases, found in an extended follow-up that provided 83 917 person-years of risk, yielded a minimum rate of leukemia that was significantly increased (six cases found, 2.26 expected; P=.028). The relative risk of leukemia in pituitary growth hormone recipients compared with the general population was 1.8 (90% confidence interval [CI], 0.82 to 7.5) for the defined follow-up and 2.6 (90% CI, 1.2 to 5.2) for the extended follow-up. Five of the six subjects who developed leukemia had antecedent cranial tumors (four craniopharyngioma, one astrocytoma) as the cause of growth hormone deficiency, and four had received radiotherapy. There was no increase in leukemia in patients with idiopathic growth hormone deficiency. The association of leukemia and craniopharyngioma was significant (P<.001). There was no excess of lymphoma in the cohort. Conclusions.-This cohort of growth hormone recipients had a significantly increased rate of leukemia compared with the age-, race-, and gender-matched general population. However, the upper bound CI of the relative risk in our population (5.2) is well below the other estimates (7.6). Compared with the general population, our study population had more possible risk factors for leukemia (radiation, tumor) that may have contributed to the excess observed. The clustering of cases of leukemia in craniopharyngioma patients should be further evaluated. C1 NICHHD,BETHESDA,MD 20892. CTR DIS CONTROL & PREVENT,ATLANTA,GA. US FDA,ROCKVILLE,MD 20857. WESTAT CORP,ROCKVILLE,MD. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. RP FRADKIN, JE (reprint author), NIDDKD,DIV DIABET ENDOCRINOL & METAB DIS,WESTWOOD BLDG,ROOM 621,BETHESDA,MD 20892, USA. NR 28 TC 93 Z9 93 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 15 PY 1993 VL 270 IS 23 BP 2829 EP 2832 DI 10.1001/jama.270.23.2829 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA MK941 UT WOS:A1993MK94100032 PM 8133622 ER PT J AU DOBYNS, WB REINER, O CARROZZO, R LEDBETTER, DH AF DOBYNS, WB REINER, O CARROZZO, R LEDBETTER, DH TI LISSENCEPHALY - A HUMAN BRAIN MALFORMATION ASSOCIATED WITH DELETION OF THE LIS1 GENE LOCATED AT CHROMOSOME-17P13 SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID MILLER-DIEKER SYNDROME; SUBMICROSCOPIC DELETIONS; INSITU HYBRIDIZATION; MUSCULAR-DYSTROPHY; DUCHENNE; REGION AB Objective.-We review the clinical phenotype, pathological changes, and results of cytogenetic and molecular genetic studies in 90 probands with lissencephaly (smooth brain) with emphasis on patients with the classical form (type I). We also describe the recent discovery of the lissencephaly gene (LIS1), deletions of which have been implicated as the cause of this disorder in many patients. Data Sources.-We have performed clinical, cytogenetic, and molecular genetic studies of 25 probands with Miller-Dieker syndrome and 65 probands with isolated lissencephaly sequence (ILS). We have further subdivided patients with ILS into those with classical lissencephaly and those with lissencephaly variants. Study Selection.-We consider primarily our own published and unpublished data, but include references to studies of other series of patients with lissencephaly. Data Synthesis.-Visible cytogenetic deletions of 17p13.3 were detected in 14 of 25 Miller-Dieker syndrome probands, and either visible cytogenetic or submicroscopic deletions in 23 (92%) of 25. Submicroscopic deletions were detected in eight of 45 patients with all types of ILS. If only ILS patients with the classical form are considered, we detected deletions in eight (38%) of 21. Conclusions.-Deletions of the lissencephaly critical region in chromosome 17p13.3, including LIS1, appear to be the most frequent cause of classical lissencephaly. Molecular cytogenetic studies, particularly fluorescence in situ hybridization, should be performed in all such patients. LIS1 shows homology to genes involved in signal transduction, which may be its function in development of the telencephalon. Other genetic causes of classical lissencephaly and genetic and nongenetic causes of other types of lissencephaly exist and are under study. C1 NATL CTR HUMAN GENOME RES,BLDG 49,ROOM 4A38,BETHESDA,MD 20892. UNIV MINNESOTA,SCH MED,DEPT NEUROL,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,SCH MED,DEPT PEDIAT,MINNEAPOLIS,MN 55455. BAYLOR COLL MED,INST MOLEC GENET,HOUSTON,TX 77030. OI Reiner, Orly/0000-0001-7560-9599; Dobyns, William/0000-0002-7681-2844 FU NICHD NIH HHS [HD20619] NR 26 TC 293 Z9 298 U1 1 U2 23 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 15 PY 1993 VL 270 IS 23 BP 2838 EP 2842 DI 10.1001/jama.270.23.2838 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA MK941 UT WOS:A1993MK94100034 PM 7907669 ER PT J AU DENNING, MF DLUGOSZ, AA HOWETT, MK YUSPA, SH AF DENNING, MF DLUGOSZ, AA HOWETT, MK YUSPA, SH TI EXPRESSION OF AN ONCOGENIC RAS(HA) GENE IN MURINE KERATINOCYTES INDUCES TYROSINE PHOSPHORYLATION AND REDUCED ACTIVITY OF PROTEIN-KINASE-C DELTA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID RAS ONCOGENE; TERMINAL DIFFERENTIATION; SARCOMA-VIRUSES; PHORBOL ESTER; CELLS; STAUROSPORINE; REQUIREMENT; INHIBITOR; PROMOTER; INVITRO AB Murine keratinocytes expressing an oncogenic ras(Ha) gene produce benign tumors in vivo and demonstrate altered responses to phorbol esters in vitro. Cultured keratinocytes transduced with the v-ras(Ha) gene (v-ras(Ha) keratinocytes) are resistant to Ca2+-induced terminal differentiation, a process that is dependent on protein kinase C (PKC) activation in normal keratinocytes. Five PKC isoforms expressed in keratinocytes (alpha, delta, epsilon, zeta, and eta) were examined for quantitative or qualitative changes in v-ras(Ha)-transformed cells. No quantitative changes were detected, but PKC delta was tyrosine-phosphorylated in v-ras(Ha) keratinocytes and in benign neoplastic keratinocyte cell lines expressing an activated allele of the c-ras(Ha) gene. Analysis of phosphorylated and non-phosphorylated forms of PKC delta from keratinocytes indicated that phosphorylated PKC delta was not stimulated by phorbol ester treatment. The protein kinase inhibitor staurosporine was able to induce differentiation in v-ras(Ha) keratinocytes and benign tumor cell lines, and concomitantly tyrosine phosphorylation of PKC delta decreased. This interaction between tyrosine kinases and PKC delta in cells expressing an oncogenic ras(Ha) gene may represent a molecular block to differentiation in neoplastic keratinocytes. C1 PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT MICROBIOL & IMMUNOL,HERSHEY,PA 17033. RP DENNING, MF (reprint author), NCI,DIV CANC ETIOL,CELLULAR CARCINOGENESIS & TUMOR PROMOT,BETHESDA,MD 20892, USA. NR 25 TC 160 Z9 161 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 15 PY 1993 VL 268 IS 35 BP 26079 EP 26081 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MK425 UT WOS:A1993MK42500013 PM 8253722 ER PT J AU EPPLER, CM HULMES, JD WANG, JB JOHNSON, B CORBETT, M LUTHIN, DR UHL, GR LINDEN, J AF EPPLER, CM HULMES, JD WANG, JB JOHNSON, B CORBETT, M LUTHIN, DR UHL, GR LINDEN, J TI PURIFICATION AND PARTIAL AMINO-ACID-SEQUENCE OF A MU-OPIOID RECEPTOR FROM RAT-BRAIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OPIATE RECEPTORS; ADENYLATE-CYCLASE; BINDING-PROTEIN; KAPPA-RECEPTOR; GUINEA-PIG; MEMBRANES; EXPRESSION; PITUITARY; CLONING; LIGAND AB A rat brain opioid receptor protein was isolated by binding [epsilon-biotinyl-Lys32]beta-endorphin to membranes, solubilizing the receptor-ligand (R.L) complex with deoxycholate-lysophosphatidylcholine and purifying on immobilized streptavidin and wheat germ agglutinin. The purified glycoprotein had a molecular mass of 60-70 kDa. Recovery of this protein was blocked by the nonselective opioid antagonist naloxone and the highly mu-selective agonist [D-Ala2,N-methyl-Phe4,Glyol5]enkephalin but not by the highly delta-selective agonist [D-Pen2,4'-Cl-Phe4 D-Pen5]enkephalin when these compounds were added as competitors at the binding step. The 60-70-kDa receptor protein co-purified through the streptavidin column with 40-kDa protein recognized by anti-G(ialpha) antibodies. GTP and Na+ influenced dissociation of the solubilized R.I-125-L complex and elution of the receptor and G protein from streptavidin in fashions consistent with the pharmacology of mu-opioid receptors. A 23-amino acid residue sequence from the purified receptor differs at 4 positions from a similar sequence in the murine delta-opioid receptor and is encoded within a novel rat brain cDNA isolated by polymerase chain reaction with oligonucleotide primers related to the murine delta-opioid receptor gene. C1 AMER CYANAMID CO,MED RES DIV,PEARL RIVER,NY 10965. UNIV VIRGINIA,DEPT INTERNAL MED CARDIOL,CHARLOTTESVILLE,VA 22908. NIDA,CTR ADDICT RES,MOLEC NEUROBIOL BRANCH,BALTIMORE,MD. JOHNS HOPKINS UNIV,DEPT NEUROL,BALTIMORE,MD 21224. UNIV VIRGINIA,DEPT PHYSIOL,CHARLOTTESVILLE,VA 22908. JOHNS HOPKINS UNIV,DEPT GEOSCI,BALTIMORE,MD 21224. RP EPPLER, CM (reprint author), AMER CYANAMID CO,AGR RES DIV,PRINCETON,NJ 08543, USA. FU NHLBI NIH HHS [R0I HL49078] NR 42 TC 49 Z9 50 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 15 PY 1993 VL 268 IS 35 BP 26447 EP 26451 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MK425 UT WOS:A1993MK42500066 PM 8253772 ER PT J AU FARINA, AR DAVISSMYTH, T GARDNER, K LEVENS, D AF FARINA, AR DAVISSMYTH, T GARDNER, K LEVENS, D TI AN EARLY RESPONSE OF AN AP1-JUND COMPLEX DURING T-CELL ACTIVATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; APE LEUKEMIA-VIRUS; DNA-BINDING ACTIVITY; PHORBOL ESTER; TRANSCRIPTIONAL ACTIVITY; HYBRIDIZATION PROBES; 5'-FLANKING REGION; INTERLEUKIN-2 GENE; ENHANCER ELEMENTS; MOUSE FIBROBLASTS AB Activated T-cell extracts contain an activity (T-AP1) composed of at least two dissociable protein components which bind to the AP1 consensus sequence in the enhancer of the gibbon ape leukemia virus (GALV)LTR (GALV-TRE). This activity is inducible by 12-O-tetradecanoyl-phorbol-14-acetate (TPA) even in the presence of protein synthesis inhibitors. Although one component of this complex (CORE) is related immunologically and biochemically to junD, it nevertheless displays significant biochemical properties which distinguish CORE from recombinant junD. The second component of the complex, flowthrough, interacts more efficiently with CORE than with recombinant junD. GALV-TRE enhancer activity is increased within 2 h in vivo with T cells treated with TPA in the presence of protein synthesis inhibitors; this increase in enhancer activity is paralleled by the increased GALV-TRE-mediated transcriptional activity present in extracts of these cells. Purified T-cell junD activates GALV-TRE-driven RNA synthesis in vitro. The rapidity and the protein synthesis-independent nature of TPA-induced T-AP1 activation suggests that this complex is involved in the earliest stages of T-cell activation. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. RI Levens, David/C-9216-2009; OI Levens, David/0000-0002-7616-922X; FARINA, Antonietta Rosella/0000-0003-0962-6088 NR 62 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 15 PY 1993 VL 268 IS 35 BP 26466 EP 26475 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MK425 UT WOS:A1993MK42500069 PM 8253775 ER PT J AU ZHU, PP REIZER, J REIZER, A PETERKOFSKY, A AF ZHU, PP REIZER, J REIZER, A PETERKOFSKY, A TI UNIQUE MONOCISTRONIC OPERON (PTSH) IN MYCOPLASMA-CAPRICOLUM ENCODING THE PHOSPHOCARRIER PROTEIN, HPR, OF THE PHOSPHOENOLPYRUVATE-SUGAR PHOSPHOTRANSFERASE SYSTEM - CLONING, SEQUENCING, AND CHARACTERIZATION OF PTSH SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HISTIDINE-CONTAINING PROTEIN; ESCHERICHIA-COLI K-12; NUCLEOTIDE-SEQUENCE; POSITIVE REGULATION; TERTIARY STRUCTURE; BACILLUS-SUBTILIS; DNA-SEQUENCE; GENE; MUTANTS; GENOME AB The region of the genome of Mycoplasma capricolum encompassing the gene (ptsH) encoding HPr, a general energy-coupling protein of the phosphoenolpyruvate: sugar phosphotransferase system, was cloned and sequenced. Examination of the sequence revealed a unique arrangement of the ptsH gene. In all other bacterial species characterized thus far, the ptsH gene is part of a polycistronic operon that includes the gene (ptsI) encoding Enzyme I of the phosphoenolpyruvate: sugar phosphotransferase system; the M. capricolum ptsH gene is part of a monocistronic operon that is situated between two open reading frames unrelated to phosphoenolpyruvate:sugar phosphotransferase system function. The gene immediately upstream of ptsH codes for a helicase, and the open reading frame immediately downstream of ptsH, although not homologous to any previously identified protein, contains a signature sequence characteristic of [C-5] cytosine-specific DNA methylases. The product of the ptsH gene has characteristics similar to the HPr protein produced by Gram-positive organisms: it has a greater sequence similarity to HPrs of Gram-positive bacteria than to those of Gram-negative organisms, it is phosphorylated by a protein kinase derived from Gram-positive organisms, and it complements sugar phosphorylation activity in Gram-positive extracts. The high calculated isoelectric point (pI = 9.18) and the absence of glutamate residues in the C-terminal region distinguish the M. capricolum HPr from all previously described HPrs. C1 NHLBI, BIOCHEM GENET LAB, BLDG 36, RM 4C-11, BETHESDA, MD 20892 USA. UNIV CALIF SAN DIEGO, DEPT BIOL, LA JOLLA, CA 92093 USA. FU NIAID NIH HHS [2RO1AI14176, 5RO1AI21702] NR 47 TC 26 Z9 30 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 15 PY 1993 VL 268 IS 35 BP 26531 EP 26540 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MK425 UT WOS:A1993MK42500076 PM 8253782 ER PT J AU HATHCOCK, KS HIRANO, H MURAKAMI, S HODES, RJ AF HATHCOCK, KS HIRANO, H MURAKAMI, S HODES, RJ TI CD44 EXPRESSION ON ACTIVATED B-CELLS - DIFFERENTIAL CAPACITY FOR CD44-DEPENDENT BINDING TO HYALURONIC-ACID SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HOMING RECEPTOR; CYTOSKELETAL INTERACTION; SURFACE GLYCOPROTEINS; MONOCLONAL-ANTIBODY; ADHESION MOLECULE; PGP-1 EXPRESSION; T-CELLS; DOMAIN; GLYCOSYLATION; LYMPHOCYTES AB CD44 expression and the functional capacity for CD44-dependent binding of hyaluronic acid (HA) were analyzed on unstimulated B cells and on B cells stimulated with a variety of polyclonal B cell activators. Whereas essentially all LPS-activated and anti-IgD-dextran-activated B cells and a subpopulation of IL-5-activated B cells expressed increased levels of cell surface CD44 relative to unstimulated B cells, only IL-5-activated CD44hi B cells constitutively bound to FITC-conjugated hyaluronic acid (FITC-HA). Preincubation of LPS or anti-IgD-dextran-activated B cells with the CD44-specific mAb IRAWB14.4 (IRA) induced a high degree of FITC-HA binding in these populations; preincubation of unstimulated B cells with this CD44-specific mAb induced minimal FITC-HA binding. In contrast, preincubation with mAb IRA failed to induce FITC-HA binding by the IL-5-activated CD44lo B cell subset. Neither the amount of constitutive FITC-HA binding nor the level of IRA-inducible FITC-HA binding correlated simply with the overall level of CD44 expressed by the different B cell populations. Biochemical analysis of immunoprecipitated CD44 molecules revealed that relative to CD44 isolated from all other populations examined, CD44 isolated from IL-5-activated B cells was of a lower molecular weight. Treatment with N-Glycanase eliminated this observed difference in molecular weight, indicating that it reflected differences in N-glycosylation of CD44 on activated B cells. Polymerase chain reaction analysis of amplified cDNA showed that each B cell population expressed a common dominant CD44 mRNA. These findings suggest that post-translational modification of CD44 and/or differential association of CD44 with other cellular components plays a critical role in activation-specific ligand binding by CD44. RP HATHCOCK, KS (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,RM 4B17,BETHESDA,MD 20892, USA. NR 51 TC 65 Z9 65 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 1993 VL 151 IS 12 BP 6712 EP 6722 PG 11 WC Immunology SC Immunology GA MM036 UT WOS:A1993MM03600010 PM 7505013 ER PT J AU MALNATI, MS CEMAN, S WESTON, M DEMARS, R LONG, EO AF MALNATI, MS CEMAN, S WESTON, M DEMARS, R LONG, EO TI PRESENTATION OF CYTOSOLIC ANTIGEN BY HLA-DR REQUIRES A FUNCTION ENCODED IN THE CLASS-II REGION OF THE MHC SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; PUTATIVE PEPTIDE TRANSPORTER; INVARIANT CHAIN PEPTIDES; RESTRICTED T-CELLS; PROTEASOME SUBUNITS; PROCESSING MUTANT; MOLECULES; GENE; VIRUS; IDENTIFICATION AB The processing pathway for the MHC class II-restricted presentation of endogenous cytosolic Ag is distinct from the class I pathway since a cytosolic form of the influenza virus A hemagglutinin, expressed by a recombinant vaccinia virus, was presented by HLA-DR in a B cell mutant lacking the TAP1 subunit of the transporter for Ag presentation (TAP). In this report, two additional B cell mutants have been used to define the requirements of this TAP1-independent processing pathway. The first mutant, .61, lacks expression of both TAP1 and TAP2 genes, and of both LMP2 and LMP7 genes encoding proteasome subunits. As expected, class I-restricted presentation of the influenza virus matrix protein was totally deficient in mutant .61. In contrast, class II-restricted presentation of both the natural cytosolic matrix and the engineered cytosolic hemagglutinin proteins was functional in mutant .61. Thus, presentation of cytosolic Ag by class II molecules is independent of both TAP subunits and of the two MHC-encoded proteasome subunits. However, this endogenous processing pathway is dependent on at least one other function encoded in the class II region of the MHC as demonstrated with the second mutant, .174, in which a large deletion eliminates all expressed class II genes. Mutant .174 transfected with HLA-DR1 genes was previously shown to be defective in the presentation of exogenous Ag but normal in the presentation of short exogenous peptides. We show here that .174(DR1) is also defective in the presentation of cytosolic matrix and hemagglutinin proteins. This similar requirement for the class II-restricted presentation of either cytosolic Ag or internalized exogenous Ag suggests that both forms of Ag are ultimately targeted to the same cellular compartment for association with class II molecules. C1 NIAID,IMMUNOGENET LAB,TWINBROOK 2,12441 PARKLAWN DR,ROCKVILLE,MD 20852. UNIV WISCONSIN,GENET LAB,MADISON,WI 53706. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 FU NIAID NIH HHS [AI-15486]; NIGMS NIH HHS [GM-07133-18] NR 32 TC 37 Z9 37 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 1993 VL 151 IS 12 BP 6751 EP 6756 PG 6 WC Immunology SC Immunology GA MM036 UT WOS:A1993MM03600014 PM 8258689 ER PT J AU MCCOY, KL PAGE, MS MERKEL, BJ INMAN, JK STUTZMAN, R AF MCCOY, KL PAGE, MS MERKEL, BJ INMAN, JK STUTZMAN, R TI DIFFERENCES AMONG VARIOUS LINEAGES OF ANTIGEN-PRESENTING CELLS IN PROCESSING EXOGENOUS ANTIGEN INTERNALIZED THROUGH TRANSFERRIN RECEPTORS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LIPOSOME-ENCAPSULATED ANTIGENS; MONOCLONAL-ANTIBODY; LYMPHOCYTES-T; CYTOCHROME-C; CLONES; HYBRIDOMAS; LYSOSOMES; ENDOSOMES; COMPLEXES; MOLECULES AB The Ag, pigeon cytochrome c, was coupled to human ferric transferrin by a heteroligation technique to target Ag into the endosomal transport pathway via transferrin receptors. The ability of various types of APC that do or do not express transferrin receptors to process exogenous Ag in their endosomes was investigated by the stimulation of Ag-specific CD4+ T cells with the transferrin-Ag conjugate in a serum-free assay. When two B lymphoma cells were the source of APC, the conjugate was significantly more potent than native Ag in activating the T cells, agreeing with our previous finding using a third B lymphoma cell. The conjugate and Ag were similarly presented by splenic B cells that lack transferrin receptors to the T cells. However, both a macrophage hyhridoma and a MHC class II-L cell transfectant hardly elicited a T cell response to the conjugate, although a response to native Ag was readily observed. These findings could not be attributed to an absence of transferrin receptors or receptor-mediated internalization of the conjugate, nor to differential expression of MHC class II molecules or Ii chain by the APC. The poor presentation of the conjugate by the L cell transfectants was associated with diminished catabolism of the conjugate, however, the macrophage hybridoma rapidly degraded the conjugate, similar to the B lymphoma cell. Peritoneal macrophages, which lack transferrin receptors, and the macrophage hybridoma induced a response to the conjugate only at concentrations that allowed internalization by fluid phase pinocytosis. The lower potency of the conjugate compared with native Ag with non-B-presenting cells suggest that these cell types process the conjugate by a different mechanism than used by B cells. Differences in the mechanism of Ag processing used by APC of distinct cell lineages may possibly influence immune responsiveness. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RP MCCOY, KL (reprint author), VIRGINIA COMMONWEALTH UNIV,DEPT MICROBIOL IMMUNOL,BOX 678 MCV STN,RICHMOND,VA 23298, USA. FU NIAID NIH HHS [AI07407, AI28422] NR 36 TC 18 Z9 18 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 1993 VL 151 IS 12 BP 6757 EP 6768 PG 12 WC Immunology SC Immunology GA MM036 UT WOS:A1993MM03600015 PM 7903098 ER PT J AU WANIDWORANUN, C STROBER, W AF WANIDWORANUN, C STROBER, W TI PREDOMINANT ROLE OF TUMOR-NECROSIS-FACTOR-ALPHA IN HUMAN MONOCYTE IL-10 SYNTHESIS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOKINE SYNTHESIS; INTERLEUKIN-10; GENE; TH1 AB In previous studies it has been shown that the bacterial endotoxin LPS induces an initial burst of inflammatory cytokine synthesis in human monocytes, which is followed by substantial IL-10 production; the IL-10 then down-regulates the inflammatory cytokine production as well as IL-10 production itself. Herein we tested the hypothesis that IL-10 production in human monocytes is under control of one of the cytokines induced by LPS. Accordingly, we cocultured purified human peripheral blood monocytes with a panel of cytokines including TNF-alpha, IL-1alpha, IL-1beta, IL-6, granulocyte macrophage-CSF, transforming growth factor-beta, and IFN-alpha and then measured IL-10 mRNA production using a semiquantitative reverse transcription-polymerase chain reaction technique. We found that TNF-alpha had a major effect on IL-10 mRNA production, inducing a 20- to 120-fold increase over baseline production. In contrast, IL-1alpha, IL-1beta, IL-6, granulocyte macrophage-CSF, transforming growth factor-beta, and IFN-alpha had little effect (<3-fold). The induction of IL-10 mRNA by TNF-alpha in monocytes was dose dependent and began between 8 and 24 h after the addition of TNF-alpha; this suggests that the increased IL-10 mRNA level was due to de novo mRNA synthesis rather than mRNA stabilization; this latter finding was corroborated by actinomycin-D time course studies, which showed that the half-life of IL-10 was less than 1 h and was not significantly altered by TNF-alpha. These studies concerning IL-10 mRNA induction by TNF-alpha were corroborated by studies of IL-10 protein secretion: TNF-alpha alone, but not IL-1alpha, IL-1beta, or IL-6 induces substantial IL-10 secretion. Furthermore, LPS induces a large amount of IL-10 secretion that is largely inhibited (50 to 75%) by anti-TNF-alpha but not by antibodies to other inflammatory cytokines. Finally, TNF-alpha augments LPS-induced IL-10 secretion. Taken together, these findings suggest that TNF-alpha is unique among the inflammatory cytokines in its role as an inducer of IL-10 in human monocytes, as such, it induces a molecule that provides negative feedback to its own production. C1 NIAID,MUCOSAL IMMUN SECT,CLIN INVEST LAB,BLDG 10,ROOM 11N238,BETHESDA,MD 20892. NR 21 TC 335 Z9 341 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 1993 VL 151 IS 12 BP 6853 EP 6861 PG 9 WC Immunology SC Immunology GA MM036 UT WOS:A1993MM03600025 PM 8258695 ER PT J AU MACNEIL, I KENNEDY, J GODFREY, DI JENKINS, NA MASCIANTONIO, M MINEO, C GILBERT, DJ COPELAND, NG BOYD, RL ZLOTNIK, A AF MACNEIL, I KENNEDY, J GODFREY, DI JENKINS, NA MASCIANTONIO, M MINEO, C GILBERT, DJ COPELAND, NG BOYD, RL ZLOTNIK, A TI ISOLATION OF A CDNA-ENCODING THYMIC SHARED ANTIGEN-1 - A NEW MEMBER OF THE LY6 FAMILY WITH A POSSIBLE ROLE IN T-CELL DEVELOPMENT SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INSULIN-RECEPTOR; STROMAL CELLS; LINKAGE MAP; SEA SNAKE; EXPRESSION; PROTEIN; ACTIVATION; THYMOCYTES; CLONES; DIFFERENTIATION AB We have previously characterized a novel mouse thymocyte marker, defined as thymic shared Ag-1 (TSA-1), present on both immature thymocytes and a subset of thymic medullary epithelial cells. MTS 35, a mAb specific for TSA-1, alters T cell differentiation when added to fetal thymic organ cultures, suggesting TSA-1 may be important for T cell development in the thymus. In this study, we describe the isolation of a cDNA encoding TSA-1 using transient expression of COS-7 cells and selection with MTS 35. The predicted amino acid sequence of this cDNA encodes a 15 to 17-kDa protein and the expressed protein is linked to the membrane via a phosphatidylinositol moiety. TSA-1 is transcriptionally active at various levels in all organs examined, suggesting that its role is not solely intrathymic. TSA-1 shares amino acid sequence homology to the mouse Ly6 multigene family, epidermal growth factor-like receptors, and to cobra venom neurotoxin. The Tsa-1 locus is located on chromosome 15 linked to Ly6 on the mouse genome. We also examined the effects of MTS 35 in fetal thymic organ cultures repopulated with two subsets of thymocytes representing defined stages of T cell development. Our results suggest that TSA-1 may play a role during positive selection and the transition from CD4+CD8+ thymocytes to the mature CD4+CD8- and CD4-CD8+ subsets. C1 DNAX RES INST MOLEC & CELLULAR BIOL INC,RES INST,DEPT IMMUNOL,901 CALIF AVE,PALO ALTO,CA 93404. NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,FREDERICK,MD 21702. MONASH UNIV,SCH MED,DEPT PATHOL & IMMUNOL,PRAHRAN,VIC 3181,AUSTRALIA. RI Zlotnik, Albert/C-3791-2011 FU NCI NIH HHS [N01-CO-74101] NR 42 TC 60 Z9 61 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 DEC 15 PY 1993 VL 151 IS 12 BP 6913 EP 6923 PG 11 WC Immunology SC Immunology GA MM036 UT WOS:A1993MM03600031 PM 8258699 ER PT J AU URBAN, JF MADDEN, KB CHEEVER, AW TROTTA, PP KATONA, IM FINKELMAN, FD AF URBAN, JF MADDEN, KB CHEEVER, AW TROTTA, PP KATONA, IM FINKELMAN, FD TI IFN INHIBITS INFLAMMATORY RESPONSES AND PROTECTIVE IMMUNITY IN MICE INFECTED WITH THE NEMATODE PARASITE, NIPPOSTRONGYLUS-BRASILIENSIS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNOGLOBULIN ISOTYPE SELECTION; STIMULATORY FACTOR-I; T-CELL SUBSETS; INTERFERON-GAMMA; MURINE LEISHMANIASIS; MONOCLONAL-ANTIBODY; ALPHA; CD4+; INTERLEUKIN-4; LYMPHOCYTES AB Mice infected with the gastrointestinal nematode parasite Nippostrongylus brasiliensis (Nb) develop responses associated with enhanced production of IL-4 (increased serum IgE levels and intestinal mucosal mastocytosis) and IL-5 (tissue and peripheral blood eosinophilia). The antagonistic effects of IFN on IL-4-mediated responses prompted an examination of the effects of IFN on the host response to Nb. Treatment with rIFN-alpha and rIFN-gamma induced a marked increase in parasite egg production (fecundity) in BALB/c mice infected with Nb and delayed intestinal expulsion of adult worms. Treatment with rIFN-alpha or rIFN-gamma also inhibited the rise in peripheral blood eosinophilia that follows inoculation with Nb, and the intensity of pulmonary perivascular tissue eosinophilia. However, Nb-induced increases in serum IgE levels and intestinal mastocytosis were only temporarily delayed by IFN. Induction of endogenous IFN production by injection of fixed Brucella abortus into mice infected with Nb also resulted in an increased worm fecundity and delayed adult worm expulsion. These effects were ablated when mice given Brucella abortus also received injections of neutralizing anti-IFN antibodies. Thus, IFN inhibit host protective immunity to Nb, perhaps by interfering with the production and effects of Th2 cytokines. C1 UNIFORMED SERV UNIV HLTH SCI,F EDWARD HEBERT SCH MED,DEPT PEDIAT,BETHESDA,MD 20814. UNIFORMED SERV UNIV HLTH SCI,F EDWARD HEBERT SCH MED,DEPT MED,BETHESDA,MD 20814. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. SCHERING PLOUGH CORP,RES INST,KENILWORTH,NJ 07033. RP URBAN, JF (reprint author), USDA ARS,BELTSVILLE AGR RES CTR,INST LIVESTOCK & POULTRY SCI,HELMINTH DIS LAB,BLDG 1040,BARC-E,BELTSVILLE,MD 20705, USA. OI Urban, Joseph/0000-0002-1590-8869 FU NIAID NIH HHS [R01-AI-21328, R29-AI-26150] NR 32 TC 88 Z9 88 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 DEC 15 PY 1993 VL 151 IS 12 BP 7086 EP 7094 PG 9 WC Immunology SC Immunology GA MM036 UT WOS:A1993MM03600048 PM 8258713 ER PT J AU TANI, Y TIAN, H LANE, HC COHEN, DI AF TANI, Y TIAN, H LANE, HC COHEN, DI TI NORMAL T-CELL RECEPTOR-MEDIATED SIGNALING IN T-CELL LINES STABLY EXPRESSING HIV-1 ENVELOPE GLYCOPROTEINS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HTLV-III/LAV ENVELOPE; SARCOMA-DERIVED CELLS; CLASS-II MHC; TYROSINE PHOSPHORYLATION; TAT PROTEIN; MONOCLONAL-ANTIBODIES; INOSITOL PHOSPHATES; SYNCYTIUM FORMATION; ANTIGEN RECEPTOR AB A series of T cell lines transfected to stably express HIV-1 envelope (env) glycoproteins were analyzed for viability and for T cell signaling. One transfectant was distinguished by its stable expression of gp120 and gp41, whereas the remainder of the T cell lines were similar to previously reported env-expressing T cells in synthesizing predominantly unprocessed env glycoprotein gp160. All of the transfectants were additionally constructed to express tat and rev proteins. None of these cell lines displayed growth abnormalities or spontaneous cell fusion, although the cell line synthesizing env gp120/gp41 could be induced to fuse and die when cocultured with a second cell expressing surface CD4. A cell line expressing only gp160 and the transfectant expressing gp160, gp120, and gp41 could be triggered normally via CD3-cross-linking as measured by protein tyrosine phosphorylation and by the induction of the CD69 activation marker. At levels of env protein expression sufficient to mediate syncytium formation and to kill cells, these HIV-1 env transfectants displayed no intrinsic T cell signaling abnormalities, suggesting that mechanisms other than a direct intracellular action of the tat or env proteins may be contributing to the deficit in Ag-specific T cell activation described subsequent to HIV infection in vivo and in vitro. C1 NIAID,IMMUNOREGULAT LAB,BLDG 10,RM 11B-13,BETHESDA,MD 20892. NR 68 TC 11 Z9 11 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 1993 VL 151 IS 12 BP 7337 EP 7348 PG 12 WC Immunology SC Immunology GA MM036 UT WOS:A1993MM03600074 PM 7903106 ER PT J AU SANDLER, DP SHORE, DL ANDERSON, JR DAVEY, FR ARTHUR, D MAYER, RJ SILVER, RT WEISS, RB MOORE, JO SCHIFFER, CA WURSTERHILL, DH MCINTYRE, OR BLOOMFIELD, CD AF SANDLER, DP SHORE, DL ANDERSON, JR DAVEY, FR ARTHUR, D MAYER, RJ SILVER, RT WEISS, RB MOORE, JO SCHIFFER, CA WURSTERHILL, DH MCINTYRE, OR BLOOMFIELD, CD TI CIGARETTE-SMOKING AND RISK OF ACUTE-LEUKEMIA - ASSOCIATIONS WITH MORPHOLOGY AND CYTOGENETIC ABNORMALITIES IN BONE-MARROW SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE MYELOID-LEUKEMIA; UNITED-STATES VETERANS; ADULT LEUKEMIA; EXPOSURES; OCCUPATION; KARYOTYPE; BENZENE; CRISIS AB Background: Cigarette smoking may be a risk factor for leukemia. No detailed biological mechanism has been proposed, but a causal link is made plausible by evidence of systemic effects of cigarette smoke and the presence in cigarette smoke of chemicals that have been associated with leukemia risk. Purpose: Our purpose was to investigate the leukemia risk associated with cigarette smoking in a multicenter case-control study of acute leukemias in adults. Methods: Adults aged 18-79 with newly diagnosed leukemia were contacted to participate in this epidemiologic study when they entered a clinical trial to be treated under protocols sponsored by Cancer and Leukemia Group B. Smoking histories for 610 patients with acute leukemia and 618 population control subjects were obtained by telephone interviews. We examined bone marrow samples and classified patients by morphology of leukocyte precursor cells according to the French-American-British (FAB) classification system and, for 378 patients, by the presence or absence of specific clonal chromosome abnormalities. We calculated odds ratios (ORs) for risk of leukemia associated with smoking cigarettes. ORs were adjusted for age, race, and sex. Results: Smoking was associated with only a modest increase in risk for leukemia overall (adjusted OR = 1.13; 95% confidence interval [CI] = 0.89-1.44). However, among participants aged 60 and older, smoking was associated with a twofold increase in risk for acute myeloid leukemia (AML) (OR = 1.96; 95% CI = 1.17-3.28) and a threefold increase in risk for acute lymphocytic leukemia (ALL) (OR = 3.40; 95% CI 0.97-11.9). Among older persons, risks increased with amount and duration of smoking. Smoking was associated with increased risk for AML classified as FAB type M2 at all ages, with ORs of 1.70 (95% CI = 1.00-2.90) for those younger than 60 and 3,50 (95% CI = 1.53-8.03) for those aged 60 and older. Smoking was also associated with ALL type L2 at all ages, with ORs of 1.72 (95% CI = 0.90-3.27) for those younger than 60 and 5.34 (95% CI = 1.03-27.6) for those who were older. Smoking was more common among patients with specific chromosome abnormalities in AML [-7 or 7q-, -Y, +13] and in ALL [t(9;22)(q34;q11)]. Conclusions: Cigarette smoking is associated with increased risk for leukemia and may lead to leukemias of specific morphologic and chromosomal types. The association varies with age. Implication: Examining discrete subtypes of disease may permit more accurate assessment of risk. As standardized morphologic classification and cytogenetic and molecular evaluation of leukemia patients becomes more common, epidemiologic studies that take advantage of these advances will begin to contribute to the identification of additional risk factors and mechanisms in acute leukemia. C1 WESTAT CORP,DURHAM,NC. NEBRASKA MED CTR,DEPT PREVENT & SOCIETAL MED,OMAHA,NE. SUNY HLTH SCI CTR,DEPT PATHOL,SYRACUSE,NY. UNIV MINNESOTA,DEPT LAB MED & PATHOL,MINNEAPOLIS,MN 55455. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. CORNELL UNIV,MED CTR,NEW YORK HOSP,CLIN ONCOL SECT,NEW YORK,NY 10021. WALTER REED ARMY MED CTR,MED ONCOL SECT,WASHINGTON,DC 20307. DUKE UNIV,MED CTR,DEPT HEMATOL ONCOL,DURHAM,NC 27710. UNIV MARYLAND,CTR CANC,CATONSVILLE,MD 21228. UNIV MARYLAND,MED CTR,CATONSVILLE,MD 21228. DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,CANC & LEUKEMIA GRP B,HANOVER,NH 03756. DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,DEPT PATHOL,HANOVER,NH 03756. NEW YORK STATE DEPT HLTH,ROSWELL PK MEM INST,DEPT MED,BUFFALO,NY 14263. RP SANDLER, DP (reprint author), NIEHS,EPIDEMIOL BRANCH,ENVIRONM & MOLEC EPIDEMIOL SECT,MAIL DROP A3-05,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Sandler, Dale/0000-0002-6776-0018 FU NCI NIH HHS [CA31946, CA33601, CA37027] NR 55 TC 74 Z9 75 U1 1 U2 3 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 15 PY 1993 VL 85 IS 24 BP 1994 EP 2003 DI 10.1093/jnci/85.24.1994 PG 10 WC Oncology SC Oncology GA ML155 UT WOS:A1993ML15500010 PM 8246285 ER PT J AU WINTER, SF SEKIDO, Y MINNA, JD MCINTIRE, D JOHNSON, BE GAZDAR, AF CARBONE, DP AF WINTER, SF SEKIDO, Y MINNA, JD MCINTIRE, D JOHNSON, BE GAZDAR, AF CARBONE, DP TI ANTIBODIES AGAINST AUTOLOGOUS TUMOR-CELL PROTEINS IN PATIENTS WITH SMALL-CELL LUNG-CANCER - ASSOCIATION WITH IMPROVED SURVIVAL SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ENCEPHALOMYELITIS SENSORY NEURONOPATHY; FREE DEFINED MEDIUM; ANTI-HU ANTIBODY; CEREBELLAR DEGENERATION; ELECTROPHORETIC TRANSFER; CIRCULATING ANTIBODIES; POLYACRYLAMIDE GELS; CLINICAL SPECIMENS; ONCOGENE PRODUCT; P53 AB Background: The frequency and clinical relevance of human antitumor immune responses is not well known, and few target antigens have been identified. Purpose: This study was designed to determine the frequency of antibodies reactive against extracts of autologous tumor cell lines and to correlate these data with survival. Methods: Serum samples were obtained from 40 lung cancer patients treated on National Cancer Institute protocols. These sera were used as probes in immunoblots against protein extracts from tumor cell lines derived from each of these patients. Results: We detected serum antibodies against autologous tumor cell proteins in 21 (58%) of the 36 patients with small-cell lung cancer (SCLC) and three (75%) of the four with non-small-cell lung cancer (NSCLC). Two patients' sera detected the p53 tumor suppressor gene product and two detected the product of the HuD gene (associated with paraneoplastic neurological syndromes) in their autologous tumor cell lysates. SCLC patients with antibodies against autologous tumor cell proteins had improved survivals compared with those in the antibody-negative group (P = .059). All patients who lived longer than 36 weeks were antitumor antibody positive. Sera, from six (86%) of seven patients with limited disease were positive for antibodies that reacted against autologous tumor cells, compared with 15 of 29 (52%) of sera from patients with extensive disease. Conclusions: Our results suggest that the sera from patients with SCLC frequently contain antibodies against tumor cell proteins and that these antibodies are associated with improved survival. Implications: These data suggest that an antitumor immune response may affect tumor growth, and that the anonymous proteins detected by antitumor antibodies in lung cancer patient sera may represent proteins involved in the development of lung cancer or in its clinical manifestations. C1 UNIV TEXAS,SW MED CTR,SIMMONS CANC CTR,5323 HARRY HINES BLVD,DALLAS,TX 75235. NCI,DIV CANC TREATMENT,NAVY MED ONCOL BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [R01CA57856] NR 43 TC 94 Z9 94 U1 0 U2 4 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 15 PY 1993 VL 85 IS 24 BP 2012 EP 2018 DI 10.1093/jnci/85.24.2012 PG 7 WC Oncology SC Oncology GA ML155 UT WOS:A1993ML15500013 PM 8246287 ER PT J AU COPELAND, KFT HAAKSMA, AGM DERSE, D GOUDSMIT, J HEENEY, JL AF COPELAND, KFT HAAKSMA, AGM DERSE, D GOUDSMIT, J HEENEY, JL TI CYTOCHEMICAL ANALYSIS OF HUMAN T-CELL LEUKEMIA-VIRUS I LTR-REGULATED BETA-GALACTOSIDASE GENE-EXPRESSION USING A NOVEL INTEGRATED CELL SYSTEM SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE BETA-GALACTOSIDASE; HUMAN T-CELL LEUKEMIA VIRUS 1 LTR 5-BROMO-4-CHLORO-3-INDOLYL-BETA-D-GALACTOPYRANOSIDE ID RECOMBINANT RETROVIRUS; LACZ GENE; LEUKEMIA; ACTIVATION; ASSAY; HIV; TRANSCRIPTION; GALACTOSIDASE; INFECTIVITY; ANTIGEN AB To develop a reporter system to study the response of,an integrated retroviral LTR and cellular and viral events which influence transcription, the 5' LTR of HTLV-1 was coupled to the Escherichia coli beta-galactosidase gene (lacZ). This construct was assembled within a vector containing the neomycin resistance gene controlled by the SV40 promoter, and introduced into HeLa cells. Expression from the LTR in one clone was upregulated by positive regulators of HTLV-1 expression, including 12-O-tetradecanoylphorbol-13-acetate (TPA) and the HTLV-1 transregulatory protein (tax), as has been previously reported using transient transfection assays. This method proved to be a rapid and reproducible assay for the measurement of integrated viral LTR activation in a single cell system. C1 FREDERICK CANC RES FACIL,VIRAL CARCINOGENESIS LAB,FREDERICK,MD. ACAD MED CENTRUM AMSTERDAM,DEPT MED VIROL,AMSTERDAM,NETHERLANDS. TNO,MBL,DEPT CHRON & INFECT DIS,VIRAL PATHOGENESIS LAB,RIJSWIJK,NETHERLANDS. OI Heeney, Jonathan/0000-0003-2702-1621 NR 25 TC 7 Z9 7 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 DEC 15 PY 1993 VL 45 IS 2 BP 161 EP 167 DI 10.1016/0166-0934(93)90100-6 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA MK822 UT WOS:A1993MK82200004 PM 8113342 ER PT J AU MCMILLAN, JP SINGER, MF AF MCMILLAN, JP SINGER, MF TI TRANSLATION OF THE HUMAN LINE-1 ELEMENT, L1HS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE REPEATED DNA; RETROTRANSPOSON; BICISTRONIC; GENE EXPRESSION ID HUMAN TRANSPOSABLE ELEMENT; TERATOCARCINOMA CELL-LINE; REVERSE-TRANSCRIPTASE; MESSENGER-RNA; GENE; DNA; INITIATION; INVITRO; VIRUS; RETROTRANSPOSONS AB Full-length RNA transcribed from the human LINE-1 (L1) element L1 Homo sapiens (L1Hs) has a 900-nt, G+C-rich, 5'-untranslated region (UTR). The 5' UTR is followed by two long open reading frames, ORF1 and ORF2, which are separated from each other by an inter-ORF region of 33 nt that includes two or three in-frame stop codons. We examine here the mechanism(s) by which the translation of L1Hs ORF1 and ORF2 is initiated. A stable hairpin structure (DELTAG = -74.8 kcal/mol), inserted at nt 661 of the 5' UTR, caused a 3- to 8-fold decrease in the in vitro and in vivo translation of either a lacZ reporter gene for ORF1 or the ORF1 polypeptide product, p40, but translation of a lacZ reporter gene in ORF2 was increased. The results are compatible with a model for ORF1 translation initiation in which the majority of ribosomes scan from a point 5' of nt 661 but suggest that ORF2 is not translated by attached ribosomes that reinitiate after the termination of ORF1 translation. Our data are compatible with a model whereby the translation of L1Hs ORF2 is initiated internally. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. CARNEGIE INST WASHINGTON,WASHINGTON,DC 20005. NR 37 TC 62 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 DEC 15 PY 1993 VL 90 IS 24 BP 11533 EP 11537 DI 10.1073/pnas.90.24.11533 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MM515 UT WOS:A1993MM51500021 PM 8265584 ER PT J AU BURBELO, PD UTANI, A PAN, ZQ YAMADA, Y AF BURBELO, PD UTANI, A PAN, ZQ YAMADA, Y TI CLONING OF THE LARGE SUBUNIT OF ACTIVATOR-1 (REPLICATION FACTOR-C) REVEALS HOMOLOGY WITH BACTERIAL-DNA LIGASES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DNA REPLICATION; ACCESSORY PROTEINS; DNA-BINDING PROTEIN ID POLYMERASE-III HOLOENZYME; CELL NUCLEAR ANTIGEN; ESCHERICHIA-COLI; NUCLEOTIDE-SEQUENCE; POLY(ADP-RIBOSE) POLYMERASE; ACCESSORY PROTEINS; MOLECULAR CHARACTERIZATION; PRIMER-TEMPLATE; COLLAGEN GENES; CDNA SEQUENCE AB We have cloned a gene encoding a DNA-binding protein by Southwestern screening of a murine cDNA library with a double-stranded oligonucleotide containing the sequence from the bidirectional promoter of the alpha1 and alpha2 collagen IV genes. The middle portion of this 1131-amino acid protein has a region homologous to bacterial DNA ligases, and the more carboxyl portion contains several domains homologous to p40, p38, p37, and p36.5 subunits of activator 1 (A1, also called replication factor C), a human replication protein complex. Western blotting revealed that antiserum generated against part of the recombinant protein reacted specifically with the 145-kDa component of the purified human A1 complex, indicating that it is the murine counterpart of the A1 p145. Characterization of the DNA-binding activity of the recombinant fusion protein by gel mobility-shift assay revealed that it had a preference for a run of pyrimidines on one strand. Deletion analysis using recombinant proteins revealed that the DNA ligase-like domain was required for DNA-binding activity. The finding that the region required for the binding of murine A1 p145 to DNA has similarity to a domain found in DNA ligases suggests that this region may be utilized by both proteins in recognizing DNA. C1 MEM SLOAN KETTERING CANC RES CTR,SLOAN KETTERING INST,PROGRAM MOLEC BIOL,NEW YORK,NY 10021. RP BURBELO, PD (reprint author), NIDR,DEV BIOL LAB,BETHESDA,MD 20892, USA. RI Burbelo, Peter/B-1027-2009 FU NIGMS NIH HHS [GM34559] NR 37 TC 60 Z9 61 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 15 PY 1993 VL 90 IS 24 BP 11543 EP 11547 DI 10.1073/pnas.90.24.11543 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MM515 UT WOS:A1993MM51500023 PM 8265586 ER PT J AU UPPULURI, S KNIPLING, L SACKETT, DL WOLFF, J AF UPPULURI, S KNIPLING, L SACKETT, DL WOLFF, J TI LOCALIZATION OF THE COLCHICINE-BINDING SITE OF TUBULIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SODIUM DODECYL-SULFATE; BRAIN BETA-1-TUBULIN; POLYACRYLAMIDE GELS; PROTEINS; SEPARATION; DRUGS; DIMER; PODOPHYLLOTOXIN; PROTEOLYSIS; SUBUNIT AB We have previously shown that rat brain tubulin, a heterodimer consisting of an alpha and beta monomer, can be covalently labeled with [H-3]colchicine by near UV irradiation. Most of the label appears in beta-tubulin. We show here that beta-tubulin can be separated and purified from SDS preparative gels and analyzed by proteolysis. Chymotrypsin yielded a labeled almost-equal-to 4-kDa band that contained two peptides. Tryptic digestion also yielded an almost-equal-to 4-kDa band containing two peptides. Sequence analysis revealed a peptide of residues 1-36 and 213-242 for chymotrypsin and a peptide of residues 1-46 and 214-241 for trypsin. To identify which peptide carried the label, limited hydrolysis of beta-tubulin was done with trypsin; this procedure yielded a labeled 16-kDa N-terminal peptide and a 35-kDa C-terminal peptide, as identified by antibodies. Isolation of these peptides and extensive digestion with trypsin yielded two labeled peptides corresponding to residues 1-46 from the 16-kDa N-terminal fragment and residues 214-241 from the 35-kDa C-terminal fragment. These results show that at least two regions in beta-tubulin are specifically involved in colchicine binding and that the span of the colchicine molecule, less-than-or-equal-to 11 angstrom, bridges these two regions in the native beta monomer. C1 NIDDKD,BIOCHEM PATHOL LAB,BETHESDA,MD 20892. NR 28 TC 135 Z9 138 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 DEC 15 PY 1993 VL 90 IS 24 BP 11598 EP 11602 DI 10.1073/pnas.90.24.11598 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MM515 UT WOS:A1993MM51500034 PM 8265596 ER PT J AU NIELSEN, S DIGIOVANNI, SR CHRISTENSEN, EI KNEPPER, MA HARRIS, HW AF NIELSEN, S DIGIOVANNI, SR CHRISTENSEN, EI KNEPPER, MA HARRIS, HW TI CELLULAR AND SUBCELLULAR IMMUNOLOCALIZATION OF VASOPRESSIN-REGULATED WATER CHANNEL IN RAT-KIDNEY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID COLLECTING DUCT; MEMBRANE; PERMEABILITY; PURIFICATION; BINDING AB Vasopressin (antidiuretic hormone) regulates body water balance by controlling water permeability of the renal collecting ducts. The control mechanisms may involve alterations in the number or unit conductance of water channels in the apical plasma membrane of collecting-duct cells. How this occurs is unknown, but indirect evidence exists for the ''shuttle'' hypothesis, which states that vasopressin causes exocytic insertion of water channel-laden vesicles from the apical cytosol. To test key aspects of the shuttle hypothesis, we have prepared polyclonal antisera against the recently cloned collecting-duct water channel protein and used the antisera in immunolocalization studies (light and electron microscopic levels) in thin and ultrathin cryosections from rat kidney. Labeling was seen exclusively in collecting-duct principal cells and inner medullary collecting-duct cells. Apical membrane labeling was intense. There was heavy labeling of abundant small subapical vesicles and of membrane structures within multivesicular bodies. In addition, labeling of basolateral plasma membranes in inner medullary collecting ducts was present. Depriving rats of water for 24 or 48 hr markedly increased collecting-duct water-channel protein expression determined by immunoblotting and immunolabeling. These results are compatible with at least two complementary modes of water-channel regulation in collecting-duct cells: (i) control of channel distribution between the apical membrane and a reservoir in subapical vesicles (shuttle hypothesis) and (ii) regulation of the absolute level of expression of water-channel protein. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. AARHUS UNIV,DEPT CELL BIOL,DK-8000 AARHUS,DENMARK. CHILDRENS HOSP MED CTR,DIV NEPHROL,BOSTON,MA 02115. FU NIDDK NIH HHS [R01 DK38874] NR 20 TC 579 Z9 581 U1 2 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 15 PY 1993 VL 90 IS 24 BP 11663 EP 11667 DI 10.1073/pnas.90.24.11663 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MM515 UT WOS:A1993MM51500047 PM 8265605 ER PT J AU ROULLET, JB XUE, H PAPPU, AS ROULLET, C HOLCOMB, S MCCARRON, DA AF ROULLET, JB XUE, H PAPPU, AS ROULLET, C HOLCOMB, S MCCARRON, DA TI MEVALONATE AVAILABILITY AND CARDIOVASCULAR FUNCTIONS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ARTERIAL SMOOTH-MUSCLE; FOREARM RESISTANCE VESSELS; HMG COA REDUCTASE; EXPERIMENTAL ATHEROSCLEROSIS; CHOLESTEROL; RELAXATION; MEMBRANE; RABBIT; HYPERCHOLESTEROLEMIA; ACETYLCHOLINE AB Data delineating the relationship between disorders of cholesterol metabolism and elevated blood pressure (BP) do not exist. We postulated that mevalonate, the metabolic precursor of endogenous cholesterol and the direct product of 3-hydroxy-3-methylglutaryl-CoA reductase, was a contributing factor for the maintenance of vascular tone and systemic BP. We conducted in vivo, ex vivo, and in vitro experiments in normotensive and hypertensive rats, where exogenous mevalonate and lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, were used, respectively, to increase or limit mevalonate availability. Mevalonate decreased BP in the whole animal without significant change in plasma cholesterol. Incubation of aortas with mevalonate attenuated their reactivity to norepinephrine and increased their response to endothelium-dependent and -independent relaxing factors. Lovastatin, in contrast, had the opposite effect in vivo and in vitro: it increased BP, enhanced vascular response to norepinephrine, and impaired endothelium-dependent and -independent relaxations. Neither agent modified cholesterol vascular content. Alteration of vascular reactivity was also observed in resistance vessels from animals pretreated with lovastatin. Our findings suggest that mevalonate availability is an unrecognized metabolic contributor to vascular tone and BP. They imply that (i) metabolites of the mevalonate pathway other than cholesterol could potentially control vascular functions and cardiovascular hemodynamics, (ii) elevated arterial pressure could be in part the consequence of primary disorders of this pathway, and (iii) pharmacological inhibition of mevalonate production as a means to lower plasma cholesterol may have an adverse impact on other cardiovascular risk factors, such as BP. C1 OREGON HLTH SCI UNIV,DIV ENDOCRINOL DIABETES & CLIN NUTR,NIDDKD,CLIN NUTR RES UNIT,PORTLAND,OR 97201. RP ROULLET, JB (reprint author), OREGON HLTH SCI UNIV,DIV NEPHROL HYPERTENS & CLIN PHARMACOL,NIDDKD,CLIN NUTR RES UNIT,PORTLAND,OR 97201, USA. FU NIDDK NIH HHS [P30 DK 40566-04] NR 27 TC 26 Z9 26 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 DEC 15 PY 1993 VL 90 IS 24 BP 11728 EP 11732 DI 10.1073/pnas.90.24.11728 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MM515 UT WOS:A1993MM51500060 PM 8265617 ER PT J AU LEBIHAN, D TURNER, R ZEFFIRO, TA CUENOD, CA JEZZARD, P BONNEROT, V AF LEBIHAN, D TURNER, R ZEFFIRO, TA CUENOD, CA JEZZARD, P BONNEROT, V TI ACTIVATION OF HUMAN PRIMARY VISUAL-CORTEX DURING VISUAL RECALL - A MAGNETIC-RESONANCE-IMAGING STUDY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE BLOOD FLOW; BLOOD OXYGENATION; HUMAN COGNITION; FUNCTIONAL NEUROIMAGING; ECHO-PLANAR IMAGING ID CEREBRAL BLOOD-FLOW; POSITRON-EMISSION TOMOGRAPHY; HUMAN STRIATE CORTEX; SENSORY STIMULATION; BRAIN OXYGENATION; MENTAL-IMAGERY; TIME; ORGANIZATION; DEPENDENCE; PATTERNS AB The degree to which the processes involved in visual perception and visual imagery share a common neuroanatomical substrate is unclear. Physiological evidence for localization of visual imagery early in the visual pathways would have important bearing on current theories of visual processing. A magnetic resonance imaging technique sensitive to regional changes in blood oxygenation was used to obtain functional activation maps in the human visual cortex. During recall of a visual stimulus, focal increases in signal related to changes in blood flow were detected in V1 and V2 cortex in five of seven subjects. These experiments show that the same areas of the early visual cortex that are excited by visual stimulation are also activated during mental representation of the same stimulus. Some of the processes used in topographically mapped cortical areas during visual perception may also be utilized during visual recall. C1 NHLBI,DEPT DIAGNOST RADIOL,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892. NHLBI,CARDIAC ENERGET LAB,BETHESDA,MD 20892. NINCDS,MED NEUROL BRANCH,BETHESDA,MD 20892. NIH,DIAGNOST RADIOL RES LAB,BETHESDA,MD 20892. RI Turner, Robert/C-1820-2008; OI Jezzard, Peter/0000-0001-7912-2251 NR 28 TC 202 Z9 202 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 DEC 15 PY 1993 VL 90 IS 24 BP 11802 EP 11805 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MM515 UT WOS:A1993MM51500075 PM 8265629 ER PT J AU JONES, CM HENRY, ER HU, Y CHAN, CK LUCK, SD BHUYAN, A RODER, H HOFRICHTER, J EATON, WA AF JONES, CM HENRY, ER HU, Y CHAN, CK LUCK, SD BHUYAN, A RODER, H HOFRICHTER, J EATON, WA TI FAST EVENTS IN PROTEIN-FOLDING INITIATED BY NANOSECOND LASER PHOTOLYSIS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CYTOCHROME-C; KINETICS; POLYPEPTIDE DYNAMICS; DENATURED STATE; OPTICAL SPECTROSCOPY ID CYTOCHROME-C; CONFORMATIONAL-CHANGES; HEMOGLOBIN; SPECTROSCOPY; DYNAMICS; COOPERATIVITY; FLUORESCENCE; ABSORPTION; BINDING; HEME AB Initiation of protein folding by light can dramatically improve the time resolution of kinetic studies. Here we present an example of an optically triggered folding reaction by using nanosecond photodissociation of the heme-carbon monoxide complex of reduced cytochrome c. The optical trigger is based on the observation that under destabilizing conditions cytochrome c can be unfolded by preferential binding of carbon monoxide to the covalently attached heme group in the unfolded state. Photodissociation of the carbon monoxide thus triggers the folding reaction. We used time-resolved absorption spectroscopy to monitor binding at the heme. Before folding begins we observe transient binding of both nonnative and native ligands from the unfolded polypeptide on a microsecond time scale. Kinetic modeling suggests that the intramolecular binding of methionine-65 and -80 is faster than that of histidine-26 and -33, even though the histidines are closer to the heme. This optical trigger should provide a powerful method for studying chain collapse and secondary structure formation in cytochrome c without any limitations in time resolution. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. FOX CHASE CANC CTR,INST CANC RES,PHILADELPHIA,PA 19111. UNIV PENN,SCH MED,DEPT BIOCHEM & BIOPHYS,PHILADELPHIA,PA 19104. RI Roder, Heinrich/B-3455-2009; Henry, Eric/J-3414-2013 OI Roder, Heinrich/0000-0003-1860-2491; Henry, Eric/0000-0002-5648-8696 FU NCI NIH HHS [CA06927]; NIGMS NIH HHS [GM35926] NR 28 TC 302 Z9 305 U1 0 U2 23 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 DEC 15 PY 1993 VL 90 IS 24 BP 11860 EP 11864 DI 10.1073/pnas.90.24.11860 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MM515 UT WOS:A1993MM51500087 PM 8265638 ER PT J AU GREENBERG, AS EGAN, JJ WEK, SA MOOS, MC LONDOS, C KIMMEL, AR AF GREENBERG, AS EGAN, JJ WEK, SA MOOS, MC LONDOS, C KIMMEL, AR TI ISOLATION OF CDNAS FOR PERILIPIN-A AND PERILIPIN-B - SEQUENCE AND EXPRESSION OF LIPID DROPLET-ASSOCIATED PROTEINS OF ADIPOCYTES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CDNA CLONING; GENE EXPRESSION; ADIPOCYTE DIFFERENTIATION; LIPOLYSIS ID GENE-EXPRESSION; APOLIPOPROTEINS; LIPOLYSIS; KINASE AB The major cAMP-dependent protein kinase (A-kinase) substrate in adipocytes is perilipin, a protein found exclusively at the surface of the lipid storage droplets. Using anti-perilipin serum, we have isolated two related classes of full-length coding cDNAs, designated perilipin A and B, from a rat adipocyte cDNA expression library. The two cDNAs derive from two mRNA species that arise by differential splicing. The mRNAs are predicted to encode perilipins A and B, proteins of 517 aa (56,870 Da) and 422 aa (46,420 Da), respectively, which share a common 406-aa N-terminal sequence. The predicted perilipin A contains peptides present in proteolytic digests of the purified 62-kDa form of perilipin from rat adipocytes, as well as the requisite consensus A-kinase phosphorylation sites. Like perilipin A, the B form is expressed in adipocytes and is associated with lipid storage droplets. Modeling of predicted secondary structures fails to reveal an underlying basis for the tenacious association of perilipins with lipid droplets. These proteins exhibit a significant sequence relationship (almost-equal-to 65% similarity through 105 aa) with only one other known protein, the adipocyte differentiation-related protein (ADRP). Like the perilipins, ADRP appears to be adipocyte-specific, which suggests that they interact in a related intracellular pathway. The molecular probes for perilipins A and B described here will permit detailed analyses of their functional role(s) in lipid metabolism. C1 CTR BIOL EVALUAT & RES,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RP GREENBERG, AS (reprint author), NIDDKD,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892, USA. NR 28 TC 189 Z9 195 U1 3 U2 11 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 DEC 15 PY 1993 VL 90 IS 24 BP 12035 EP 12039 DI 10.1073/pnas.90.24.12035 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MM515 UT WOS:A1993MM51500123 PM 7505452 ER PT J AU OSAWA, Y DARBYSHIRE, JF MEYER, CA ALAYASH, AI AF OSAWA, Y DARBYSHIRE, JF MEYER, CA ALAYASH, AI TI DIFFERENTIAL SUSCEPTIBILITIES OF THE PROSTHETIC HEME OF HEMOGLOBIN-BASED RED-CELL SUBSTITUTES - IMPLICATIONS IN THE DESIGN OF SAFER AGENTS SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID BIS(3,5-DIBROMOSALICYL) FUMARATE; LIPID-PEROXIDATION; BLOOD SUBSTITUTE; IRON RELEASE; CROSS-LINK; MYOGLOBIN; DEGRADATION; PROTEIN; AUTOXIDATION; HEMOLYSIS AB One approach to the development of an effective red cell substitute has been chemical modification of human hemoglobin to optimize oxygen transport and plasma half-life. Human hemoglobin A(0) and two of these modified hemoglobins, one prepared from the cross-linking of the alpha-chains at lysine residue 99 by bis(3,5-dibromosalicyl)fumarate (Hb-DBBF) and the other by acylation of lysine residue 82 of the beta-chain by mono-(3,5-dibromosalicyl)fumarate (Hb-FMDA), were tested by HPLC for their susceptibility to oxidative damage caused by H2O2. Such oxidative insult may occur during ischemia and reperfusion of tissues after transfusion of red cell substitutes to patients with hypovolemic shock and trauma. Hb-DBBF was extremely susceptible to damage of its heme and protein moieties with stoichiometric amounts of H2O2, whereas Hb-FMDA was highly resistant, even at 10-fold molar excess and at an acidic pH of 4.7. Hemoglobin A(0) was of intermediate susceptibility, exhibiting alteration of heme and protein moieties at acidic but not neutral pH. Since the degradation of heme can release the potentially toxic agent iron, Hb-FMDA may be a more promising candidate than Hb-DBBF for development as a red cell substitute. A similar approach may be used to assess the susceptibility of other hemoglobin-based red cell substitutes to oxidative damage in order to determine the molecular basis of heme and protein alteration. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. RP OSAWA, Y (reprint author), NHLBI,CHEM PHARMACOL LAB,BLDG 10,RM 8N110,BETHESDA,MD 20892, USA. NR 39 TC 38 Z9 38 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD DEC 14 PY 1993 VL 46 IS 12 BP 2299 EP 2305 DI 10.1016/0006-2952(93)90621-3 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MN604 UT WOS:A1993MN60400023 PM 8274164 ER PT J AU SACKETT, DL VARMA, JK AF SACKETT, DL VARMA, JK TI MOLECULAR MECHANISM OF COLCHICINE ACTION - INDUCED LOCAL UNFOLDING OF BETA-TUBULIN SO BIOCHEMISTRY LA English DT Article ID ALPHA-TUBULIN; MICROTUBULE POLYMERIZATION; GTP HYDROLYSIS; DYNAMIC INSTABILITY; LIMITED PROTEOLYSIS; BINDING; INHIBITION; BRAIN; DIMER; ANTIBODIES AB Colchicine, the classic antimitotic poison, disrupts cell division by preventing proper assembly of microtubules in the mitotic spindle. Colchicine is known to act by binding to tubulin, the heterodimeric subunit of microtubules. How this binding to tubulin changes the structure of the protein and results in polymerization poisoning has not been characterized. The structural locus of spectroscopically detected conformational changes induced by colchicine is unknown. We report here that colchicine induces the unfolding of a small region in the carboxyl-terminal region of beta-tubulin, around Arg-390. This unfolding isdetectedbyproteolysiswithtrypsinandchymotrypsin. ChymotrypsincleavesthisregionafterPhe-389, and trypsin cleaves after Lys-392. The unfolded region appears to be the carboxyl end of an amphipathic helix in the absence of colchicine, and we propose that this unfolding prevents contacts necessary for assembly. Our results suggest that beta-tubulin is exposed on the growing end of the microtubule, which provides a mechanism for coupling GTP hydrolysis to polymerization. RP SACKETT, DL (reprint author), NIDDKD,BIOCHEM PHARMACOL LAB,BLDG 8,ROOM 2A23,BETHESDA,MD 20892, USA. NR 53 TC 84 Z9 88 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 14 PY 1993 VL 32 IS 49 BP 13560 EP 13565 DI 10.1021/bi00212a023 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MM035 UT WOS:A1993MM03500023 PM 8257691 ER PT J AU MANNS, A CLEGHORN, FR FALK, R HANCHARD, B JAFFE, ES BARTHOLOMEW, C HARTGE, P BENICHOU, J BLATTNER, WA AF MANNS, A CLEGHORN, FR FALK, R HANCHARD, B JAFFE, ES BARTHOLOMEW, C HARTGE, P BENICHOU, J BLATTNER, WA TI ROLE OF HTLV-I IN DEVELOPMENT OF NON-HODGKIN-LYMPHOMA IN JAMAICA AND TRINIDAD-AND-TOBAGO SO LANCET LA English DT Article ID T-CELL LEUKEMIA; VIRUS TYPE-I; RISK-FACTORS; DETERMINANTS; RETROVIRUS; INFECTION; MODEL; AGE AB Human T-cell lymphotropic virus type I (HTLV-I) has been implicated in the aetiology of adult T-cell leukaemia/lymphoma in Japan and elsewhere, particularly the Caribbean. We have carried out parallel case-control studies in Jamaica and in Trinidad and Tobago to quantify the role of HTLV-I in the development of non-Hodgkin lymphoma (NHL). 135 cases of NHL were enrolled in Jamaica and 104 in Trinidad and Tobago. Controls were selected from patients treated in the same wards or clinics at the same time as the cases. Overall, patients with NHL were 10 times more likely than were controls to be seropositive for HTLV-I (Jamaica odds ratio 10.3 [95% CI 6.0-18.0], Trinidad and Tobago 14.4 [7.6-27.2]). In both countries the association between NHL and HTLV-I was greatest for T-cell lymphomas (18.3 [9.5-35.6] and 63.3 [25-167]). Among T-cell lymphomas especially, there was no significant difference between men and women in the association between NHL and HTLV-I, but there was a significant inverse relation between age and likelihood of HTLV-I seropositivity. B-cell lymphomas were predominant in the older age groups and were not associated with HTLV-I seropositivity. These findings are consistent with the hypothesis that early life exposure to HTLV-I is important for risk of subsequent ATL. Prevention of vertical transmission of HTLV-I could reduce by 70-80% cases of NHL in people under 60 years in this region. C1 UNIV W INDIES,DEPT PATHOL,KINGSTON 7,JAMAICA. NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,DIV CANC ETIOL,EPIDEMIOL & BLOSTAT PROGRAM,BETHESDA,MD 20892. DEPT MED,PORT OF SPAIN,TRINID & TOBAGO. FU NCI NIH HHS [NCI N01-CP-61002, NCI N01-CP-31006] NR 30 TC 54 Z9 55 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD DEC 11 PY 1993 VL 342 IS 8885 BP 1447 EP 1450 DI 10.1016/0140-6736(93)92931-I PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA ML217 UT WOS:A1993ML21700007 PM 7902480 ER PT J AU RADER, DJ IKEWAKI, K DUVERGER, N FEUERSTEIN, I ZECH, L CONNOR, W BREWER, HB AF RADER, DJ IKEWAKI, K DUVERGER, N FEUERSTEIN, I ZECH, L CONNOR, W BREWER, HB TI VERY-LOW HIGH-DENSITY-LIPOPROTEINS WITHOUT CORONARY ATHEROSCLEROSIS SO LANCET LA English DT Article ID APOLIPOPROTEIN-A-I; ISCHEMIC HEART-DISEASE; INVIVO METABOLISM; PARTICLES; DEFICIENCY; MUTATION; GENE AB Epidemiological studies have established that concentrations of plasma high-density lipoproteins (HDL) are inversely associated with premature atherosclerosis, but the physiological basis of this relationship remains unknown. We investigated 5 probands with very low plasma HDL. None had clinical or biochemical findings typical of the known genetic disorders with low HDL nor had evidence of premature coronary atherosclerosis by sensitive diagnostic methods. All 5 probands and the son of 1 of them had rapid catabolism of the HDL apolipoproteins A-I and A-II. These results indicate that not all people with low HDL are necessarily at risk of premature coronary heart disease and that further investigation is required before decisions can be made about their management. C1 OREGON HLTH SCI UNIV,DEPT MED,CLIN NUTR & LIPID METAB SECT,PORTLAND,OR 97201. RP RADER, DJ (reprint author), NHLBI,MOLEC DIS BRANCH,BLDG 10,ROOM 7N117,BETHESDA,MD 20892, USA. FU NCRR NIH HHS [RR334]; NIDDK NIH HHS [DK40566] NR 21 TC 49 Z9 49 U1 0 U2 2 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD DEC 11 PY 1993 VL 342 IS 8885 BP 1455 EP 1458 DI 10.1016/0140-6736(93)92933-K PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA ML217 UT WOS:A1993ML21700009 PM 7902482 ER PT J AU URNOVITZ, HB CLERICI, M SHEARER, GM GOTTFRIED, TD ROBISON, DJ LUTWICK, LI MONTAGNIER, L LANDERS, DV AF URNOVITZ, HB CLERICI, M SHEARER, GM GOTTFRIED, TD ROBISON, DJ LUTWICK, LI MONTAGNIER, L LANDERS, DV TI HIV-1 ANTIBODY SERUM NEGATIVITY WITH URINE POSITIVITY SO LANCET LA English DT Note AB 7 individuals who were negative for HIV-1 antibody in a licensed serum enzyme immunoassay (EIA) were positive in a urine EIA and western blot (WB). Follow-up in individuals by use of a cell-mediated immune response showed 1 positive and 1 negative for HIV-1 peptide reactivity. In a second study, 4 out of 5 subjects positive by urine EIA and indeterminate or negative by serum WB were HIV-1 peptide positive in the cell-mediated immune test. Comparison of cell-mediated responses with urine antibody responses may help to resolve discrepant HIV-1 results. C1 MAIMONIDES HOSP,BROOKLYN,NY 11219. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. INST PASTEUR,F-75724 PARIS 15,FRANCE. NCI,BETHESDA,MD 20892. RP URNOVITZ, HB (reprint author), CALYPTE BIOMED CORP,BERKELEY,CA 94710, USA. NR 8 TC 23 Z9 24 U1 1 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD DEC 11 PY 1993 VL 342 IS 8885 BP 1458 EP 1459 DI 10.1016/0140-6736(93)92934-L PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA ML217 UT WOS:A1993ML21700010 PM 7902483 ER PT J AU SADOFSKY, MJ HESSE, JE MCBLANE, JF GELLERT, M AF SADOFSKY, MJ HESSE, JE MCBLANE, JF GELLERT, M TI EXPRESSION AND V(D)J RECOMBINATION ACTIVITY OF MUTATED RAG-1 PROTEINS SO NUCLEIC ACIDS RESEARCH LA English DT Article ID B-CELLS; GENE; REARRANGEMENT; MICE AB The products of the RAG-1 and RAG-2 genes ([1], [2]) are essential for the recombination of the DNA encoding the antigen receptors of the developing immune system. Little is known of the specific role these genes play. We have explored the sequences encoding mouse RAG-1 by deleting large parts of the gene and by introducing local sequence changes. We find that a RAG-1 gene with 40% of the coding region deleted still retains its recombination function. In addition, a series of small deletions within the strongly conserved remaining 60% of the coding region was tested. Nine out of ten of these prove unable to provide RAG-1 activity, but one is quite active. Certain peptide sequences were also specifically targeted for mutagenesis. The RAG-1 protein generated from this expression system is transported to the nucleus and is degraded with a 15 minute half-life. The fate of the proteins made by the deletion mutants were also assessed. Transport of RAG-1 protein to the nucleus was found even with the most extensive deletions studied. The functionality of the deleted proteins is discussed with relation to an alignment of RAG-1 sequences from five animal species. C1 NIDDK,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 22 TC 159 Z9 162 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC 11 PY 1993 VL 21 IS 24 BP 5644 EP 5650 DI 10.1093/nar/21.24.5644 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MM781 UT WOS:A1993MM78100017 PM 8284210 ER PT J AU BUONANNO, A EDMONDSON, DG HAYES, WP AF BUONANNO, A EDMONDSON, DG HAYES, WP TI UPSTREAM SEQUENCES OF THE MYOGENIN GENE CONVEY RESPONSIVENESS TO SKELETAL-MUSCLE DENERVATION IN TRANSGENIC MICE SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RECEPTOR ALPHA-SUBUNIT; MESSENGER-RNA LEVELS; LOOP-HELIX PROTEINS; ELECTRICAL-ACTIVITY; ACETYLCHOLINE-RECEPTORS; NEUROMUSCULAR-JUNCTIONS; REGULATORY FACTORS; GAMMA-SUBUNIT; SOLEUS MUSCLE; BINDING-SITES AB Myogenin, as well as other MyoD-related skeletal muscle-specific transcription factors, regulate a large number of skeletal muscle genes during myogenic differentiation. During later development, innervation suppresses myogenin expression in the fetal hind limb musculature. Denervation of skeletal muscle reverses the effects of the nerve, and results in the reactivation of myogenin expression, as well as of other embryonic muscle proteins. Here we report that myogenin upstream sequences confer tissue- and developmental-specific expression in transgenic mice harboring a myogenin/chloramphenicol acetyltransferase (CAT) reporter construct. Using in situ hybridization to analyze serial sections of E12.5 embryos, we found co-localization of CAT and endogenous myogenin transcripts in the primordial muscle of the head and limbs, in the intercostal muscle masses, and in the most caudal somites. Later in development, we observed that the expression of the transgene and endogenous myogenin gene continued to be restricted to skeletal muscle but decreased shortly after birth; a period that coincides with the innervation of secondary myotubes. Furthermore, denervation of the mouse hind limbs induced a 10-fold accumulation of CAT and endogenous myogenin transcripts by 1 day after sciatic nerve resection; a 25-fold increase was observed by 4 days after denervation. Interestingly, we observed that the accumulation of CAT enzyme activity lagged considerably with respect to the increase in CAT transcripts. Our results indicate that the cis-acting elements that temporally and spatially confine transcription of the gene during embryonic development, and that mediate the responses to innervation and denervation of muscle, lie within the upstream sequences analyzed in these studies. C1 UNIV TEXAS,M D ANDERSON CANC CTR,DEPT BIOCHEM & MOLEC BIOL,HOUSTON,TX 77030. RP BUONANNO, A (reprint author), NIH,DEV NEUROBIOL LAB,BETHESDA,MD 20892, USA. FU NICHD NIH HHS [N01-HD-0-2911] NR 80 TC 21 Z9 24 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC 11 PY 1993 VL 21 IS 24 BP 5684 EP 5693 DI 10.1093/nar/21.24.5684 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MM781 UT WOS:A1993MM78100024 PM 8284216 ER PT J AU CHUVPILO, S SCHOMBERG, C GERWIG, R HEINFLING, A REEVES, R GRUMMT, F SERFLING, E AF CHUVPILO, S SCHOMBERG, C GERWIG, R HEINFLING, A REEVES, R GRUMMT, F SERFLING, E TI MULTIPLE CLOSELY-LINKED NFAT-OCTAMER AND HMG I(Y) BINDING-SITES ARE PART OF THE INTERLEUKIN-4 PROMOTER SO NUCLEIC ACIDS RESEARCH LA English DT Article ID T-CELL ACTIVATION; LYMPHOCYTE-SPECIFIC FACTORS; GROUP PROTEIN HMG-I(Y); CYCLOSPORINE-A; GENE-EXPRESSION; GLUCOCORTICOID RECEPTOR; CHROMOSOMAL GENE; NUCLEAR FACTOR; BETA GENE; IL-2 GENE AB We show here that the immediate upstream region (from position -12 to -270) of the murine Interleukin 4 (Il-4) gene harbors a strong cell-type specific transcriptional enhancer. In T lymphoma cells, the activity of the Il-4 promoter/enhancer is stimulated by phorbol esters, Ca++ ionophores and agonists of protein kinase A and inhibited by low doses of the immunosuppressant cyclosporin A. The Il-4 promoter/enhancer is transcriptionally inactive in B lymphoma cells and HeLa cells. DNase I footprint protection experiments revealed six sites of the Il-4 promoter/enhancer to be bound by nuclear proteins from lymphoid and myeloid cells. Among them are four purine boxes which have been described to be important sequence motifs of the Il-2 promoter. They contain the motif GGAAA and are recognized by the inducible and cyclosporin A-sensitive transcription factor NFAT-1. Three of the Il-4 NFAT-1 sites are closely linked to weak binding sites of Octamer factors. Several purine boxes and an AT-rich protein-binding site of the Il-4 promoter are also recognized by the high mobility group protein HMG I(Y). Whereas the binding of NFAT-1 and Octamer factors enhance the activity of the Il-4 promoter, the binding of HMG I(Y) suppresses its activity and, therefore, appears to be involved in the suppression of Il-4 transcription in resting T lymphocytes. C1 UNIV WURZBURG,INST PATHOL,BIOZENTRUM,AM HUBLAND,J SCHNEIDER STR 7,D-97080 WURZBURG,GERMANY. NICHHD,BETHESDA,MD 20892. UNIV WURZBURG,INST BIOCHEM,BIOZENTRUM,D-97080 WURZBURG,GERMANY. NR 59 TC 186 Z9 186 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC 11 PY 1993 VL 21 IS 24 BP 5694 EP 5704 DI 10.1093/nar/21.24.5694 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MM781 UT WOS:A1993MM78100025 PM 8284217 ER PT J AU KISS, A AGUILERA, G AF KISS, A AGUILERA, G TI REGULATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS DURING CHRONIC STRESS - RESPONSES TO REPEATED INTRAPERITONEAL HYPERTONIC SALINE INJECTION SO BRAIN RESEARCH LA English DT Article DE REPEATED STRESS; CORTICOTROPIN RELEASING HORMONE; VASOPRESSIN; PARAVENTRICULAR NUCLEUS; ADRENOCORTICOTROPIN; GLUCOCORTICOID ID CORTICOTROPIN-RELEASING-FACTOR; FACTOR MESSENGER-RNA; ADRENOCORTICOTROPIN SECRETION; ARGININE VASOPRESSIN; WATER-DEPRIVATION; PARAVENTRICULAR NUCLEUS; IMMOBILIZATION STRESS; ENHANCES VASOPRESSIN; RAT; HORMONE AB Chronic osmotic stress inhibits, while repeated physical stress can increase pituitary ACTH responsiveness to a novel stress. The interaction between these effects was studied in rats subjected to repeated i.p. injection of hypertonic saline, a strong aversive stimulus with osmotic and painful and psychological stress components, for 14 days. Hypertonic saline injection caused marked drinking responses, transient increases in plasma vasopressin (VP), and marked increases in VP mRNA and irVP in magnocellular cell bodies in the hypothalamus. Parvicellular activity was also enhanced as indicated by increases in VP immunostaining in the external zone of the median eminence and CRH mRNA and irCRH in the PVN. Plasma ACTH levels increased 10-fold after 30 min hypertonic saline injection, returning to basal levels in 4 h, and there was no desensitization of the ACTH responses after repeated injections (from basal values of 76 +/- 10 to 782 +/- 57, 788 +/- 83 and 779 +/- 31 pg/ml 30 min after the first, 4th and 14th injection, respectively). Basal ACTH levels were normal 24 h after the last injection, but pituitary POMC mRNA levels were increased by 95%, and ACTH responses to a novel stress (15 min immobilization) were significantly larger than in controls (P < 0.01) despite increases in morning plasma corticosterone levels (1.5 +/- 0.4 and 9.2 +/- 3.1 mu g/dl in controls and stressed rats, respectively). Enhancing the osmotic component of the stress by daily withdrawal of the drinking water for 8 h following the injection, or by administration of 0.9% saline as drinking fluid, did not prevent the increases in CRH mRNA and hypersensitivity of the ACTH response to the novel stress. The data show that physical and psychological components of the stress overcome the inhibitory effect of chronic osmotic stimulation on ACTH secretion, and emphasizes the relationship between parvicellular activation and HPA hypersensitivity during chronic stress. C1 NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,RM 10N262,BETHESDA,MD 20892. NR 43 TC 88 Z9 89 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD DEC 10 PY 1993 VL 630 IS 1-2 BP 262 EP 270 DI 10.1016/0006-8993(93)90665-A PG 9 WC Neurosciences SC Neurosciences & Neurology GA MK032 UT WOS:A1993MK03200031 PM 8118692 ER PT J AU SATHYANARAYANA, BK WLODAWER, A AF SATHYANARAYANA, BK WLODAWER, A TI X-RAY CRYSTAL-STRUCTURE AND COMPUTER MODELING STUDIES OF HIV PROTEASE AND ITS INHIBITOR COMPLEXES SO CURRENT SCIENCE LA English DT Review ID HUMAN IMMUNODEFICIENCY VIRUS-1; RESOLUTION; REFINEMENT; PROTEINS AB HIV-1 protease is essential for the replication of HIV or the acquired immunodeficiency (AIDS) virus and is considered as an attractive target for the design of specific inhibitors. In order to design drugs which inhibit the action of HIV protease, it is essential to obtain the 3-D structures of these proteases. The native HIV protease and the very first inhibitor complex of the protease were studied at our laboratory and in this article we summarize the X-ray structure analysis and molecular modelling studies of the HIV-1 protease both in its native as well as with different inhibitor complexes studied both at our laboratory as well as laboratories elsewhere. RP SATHYANARAYANA, BK (reprint author), NCI,FREDERICK CANC RES & DEV CTR,MACROMOLEC STRUCT LAB,BRP ABL,POB B,FREDERICK,MD 21702, USA. NR 27 TC 3 Z9 3 U1 0 U2 1 PU CURRENT SCIENCE ASSN PI BANGALORE PA C V RAMAN AVENUE, PO BOX 8005, BANGALORE 560 080, INDIA SN 0011-3891 J9 CURR SCI INDIA JI Curr. Sci. PD DEC 10 PY 1993 VL 65 IS 11 BP 835 EP 847 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MU674 UT WOS:A1993MU67400013 ER PT J AU HE, XS RAYMON, LP MATTSON, MV ELDEFRAWI, ME DECOSTA, BR AF HE, XS RAYMON, LP MATTSON, MV ELDEFRAWI, ME DECOSTA, BR TI FURTHER-STUDIES OF THE STRUCTURE-ACTIVITY-RELATIONSHIPS OF 1-[1-(2-BENZO[B]THIENYL)CYCLOHEXYL]PIPERIDINE - SYNTHESIS AND EVALUATION OF 1-(2-BENZO[B]THIENYL)-N,N-DIALKYLCYCLOHEXYLAMINES AT DOPAMINE UPTAKE AND PHENCYCLIDINE BINDING-SITES SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ANTICONVULSANT MK-801; RECEPTOR; POTENT; ANALOG; CONFIGURATION; AFFINITY; COMPLEX; BRAIN; PCP AB We previously reported (J. Med, Chem. 1993, 36, 1188-1193) that changes to the ring size of the piperidine and cyclohexyl rings of the high-affinity and selective dopamine (DA)-uptake inhibitor 1-[1-(2-benzo[b]thienyl) cyclohexyl] piperidine (BTCP, 2) caused different, and in some cases opposite, changes in affinity for sites on the DA transporter labeled by [H-3]BTCP and [H-3]-cocaine. These results suggested that the radioligands label different sites on the transporter. In the present study, we extend the structure-activity relationships (SAR) of BTCP by studying the binding characteristics of a series of N,N-disubstituted 1-(a-benzo[b]thienyl) cyclohexylamines 7-32 at the DA transporter. Cyclohexyl was selected as opposed to other ring sizes since it corresponds to BTCP. The binding results indicate that a considerable degree of structural variation is permitted for the N-substituents, while still retaining nanomolar affinity for sites on the transporter (studied in rat forebrain homogenates). As observed in our earlier study, the differential effects of structural change on binding to sites on the DA transporter labeled by these radioligands suggests that they are different and distinct binding sites. In general, and up to a point, increasing the size and lipophilicity of the N substituents resulted in improvements in binding but appeared to have less predictable effects on DA-uptake inhibition (as measured in rat brain synaptosomes). The binding of these compounds to sites labeled by [H-3]BTCP appeared to correlate best with IC50 for DA-uptake inhibition. To our surprise, the monoalkyl N-substituted BTCP derivatives displayed the highest affinity for the DA transporter of all the compounds in this series. For example, the N-(cyclopropylmethyl) derivative 14 displayed IC50's = 23 nM ([H-3]cocaine) and 1 nM ([H-3]-BTCP), and the N-butyl derivative 10 showed IC50's = 60 nM ([H-3]cocaine) and 0.3 nM ([H-3]BTCP). BTCP exhibited IC50's of 39 nM ([H-3]cocaine) and 5 nM ([H-3]BTCP) in this assay. The observation that N,N-dibutyl derivative 31 exhibited low ratios of IC50 [H-3] cocaine/IC50 DA reuptake and IC50 [H-3]BTCP/IC50 DA reuptake suggests that it may be a potential candidate for cocaine antagonism studies. The effect of additional amino, amide, and aromatic groups on the N-substituents was examined, and the results are discussed. The failure of all of the compounds in this series to bind phencyclidine receptors coupled with their high affinity and range of selectivities at the DA transporter identifies many of them as useful tools for probing the mode of action of BTCP at this site. C1 NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,DEPT PHARMACOL & EXPTL THERAPEUT,BALTIMORE,MD 21201. FU NIDA NIH HHS [DA03680-07] NR 19 TC 16 Z9 16 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 10 PY 1993 VL 36 IS 25 BP 4075 EP 4081 DI 10.1021/jm00077a011 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA MM142 UT WOS:A1993MM14200011 PM 8258830 ER PT J AU CLERICI, M LUCEY, DR BERZOFSKY, JA PINTO, LA WYNN, TA BLATT, SP DOLAN, MJ HENDRIX, CW WOLF, SF SHEARER, GM AF CLERICI, M LUCEY, DR BERZOFSKY, JA PINTO, LA WYNN, TA BLATT, SP DOLAN, MJ HENDRIX, CW WOLF, SF SHEARER, GM TI RESTORATION OF HIV-SPECIFIC CELL-MEDIATED IMMUNE-RESPONSES BY INTERLEUKIN-12 IN-VITRO SO SCIENCE LA English DT Article ID LYMPHOCYTE MATURATION FACTOR; STIMULATORY FACTOR; RECOMBINANT INTERLEUKIN-2; HETERODIMERIC CYTOKINE; IDENTIFICATION; PURIFICATION; INDUCTION; SYNERGY; PEPTIDE AB Peripheral blood mononuclear cells (PBMCs) from many asymptomatic individuals infected with human immunodeficiency virus-type 1 (HIV) are unresponsive as measured by in vitro T cell proliferation and interleukin-2 (IL-2) production to influenza virus and synthetic peptides of HIV envelope (Env). Strong influenza virus- and Env-stimulated IL-2 responses and T cell proliferation were restored when cultures were stimulated in the presence of IL-12. Interferon-gamma production by PBMCs from HIV seropositive (HIV+) patients was also restored with IL-12. Furthermore, in vitro antigen-specific production of IL-2 and proliferation of PBMCs from HIV- donors were suppressed by antibody to IL-12, but were not enhanced by addition of exogenous IL-12. Thus, IL-12 may be limiting in PBMCs from HIV+ but not HIV- individuals. These findings demonstrate that IL-12 can restore HIV-specific cell-mediated immunity in vitro in HIV-infected individuals and suggest a potential use of IL-12 in augmenting the diminished immunologic functions associated with HIV infection. C1 NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B-17,BETHESDA,MD 20892. GENET INST INC,CAMBRIDGE,MA 02140. NCI,METAB BRANCH,BETHESDA,MD 20892. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. WILFORD HALL USAF MED CTR,HIV UNIT,LACKLAND AFB,TX 78236. RI Wynn, Thomas/C-2797-2011; Hendrix, Craig/G-4182-2014 OI Hendrix, Craig/0000-0002-5696-8665 NR 33 TC 406 Z9 411 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 10 PY 1993 VL 262 IS 5140 BP 1721 EP 1724 DI 10.1126/science.7903123 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ML220 UT WOS:A1993ML22000038 PM 7903123 ER PT J AU KOST, RG HILL, EL TIGGES, M STRAUS, SE AF KOST, RG HILL, EL TIGGES, M STRAUS, SE TI BRIEF REPORT - RECURRENT ACYCLOVIR-RESISTANT GENITAL HERPES IN AN IMMUNOCOMPETENT PATIENT SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Note ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; SIMPLEX VIRUS TYPE-2; ALTERED SUBSTRATE-SPECIFICITY; VARICELLA-ZOSTER VIRUS; THYMIDINE KINASE GENE; ORAL ACYCLOVIR; DOUBLE-BLIND; PLAQUE AUTORADIOGRAPHY; NUCLEOTIDE-SEQUENCE; THERAPY C1 NIAID, CLIN INVEST LAB,MED VIROL SECT,BLDG 10, ROOM 11N228, BETHESDA, MD 20892 USA. BURROUGHS WELLCOME CO, DIV VIROL, RES TRIANGLE PK, NC 27709 USA. CHIRON CORP, EMERYVILLE, CA USA. NR 44 TC 126 Z9 128 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 9 PY 1993 VL 329 IS 24 BP 1777 EP 1782 DI 10.1056/NEJM199312093292405 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA MK096 UT WOS:A1993MK09600005 PM 8232486 ER PT J AU TUMMINIA, SJ RAO, PV ZIGLER, JS RUSSELL, P AF TUMMINIA, SJ RAO, PV ZIGLER, JS RUSSELL, P TI XENOBIOTIC INDUCTION OF QUINONE OXIDOREDUCTASE ACTIVITY IN LENS EPITHELIAL-CELLS SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE OXIDATION; ZETA-CRYSTALLIN; DT-DIAPHORASE; XENOBIOTIC ID GUINEA-PIG LENS; ZETA-CRYSTALLIN; NAD(P)H-QUINONE REDUCTASE; DT-DIAPHORASE; PROTEIN; IDENTIFICATION; PURIFICATION; NADPH; ANTIOXIDANTS; MENADIONE AB Xenobiotic regulatory elements have been identified for enzymes which ameliorate oxidative damage in cells. Zeta (zeta)-crystallin, a taxon-specific enzyme/crystallin shown to be a never NADPH-dependent quinone reductase, is found in a number of tissues and cell types. This study shows that zeta-crystallin is present in mouse lens epithelium, as well as in the alpha TN4 mouse lens epithelial cell line. To determine whether zeta-crystallin is an inducible quinone reductase, cell cultures were exposed to the xenobiotics, 1,2-naphthoquinone and beta-naphthoflavone. Assays of cellular homogenates showed that quinone reductase activity was stimulated greater than 70% and 90%, respectively, over the control cells. This observed activity was sensitive to dicumarol, a potent inhibitor of quinone reductase activity. 1,2-Naphthoquinone- and beta-naphthoflavone-exposed cells were found to exhibit 1.47- and 1.68-fold increases, respectively, in zeta-crystallin protein concentration. A comparable increase in zeta-crystallin mRNA was indicative of an induction in zeta-crystallin expression in response to naphthalene challenge. Lens epithelial cells were also checked for DT-diaphorase, a well-known cellular protective enzyme which can catalyze the two-electron reduction of quinones. Slot blot analyses indicated that alpha TN4 cells exposed to 1,2-naphthoquinone and beta-naphthoflavone exhibited 2.71- and 6.81-fold increases in DT-diaphorase concentration when compared to the control cells. The data suggest that while DT-diaphorase is most likely responsible for the majority of the observed increase in quinone reductase activity, the zeta-crystallin gene also undergoes activation which is apparently mediated by a xenobiotic-responsive element. RP TUMMINIA, SJ (reprint author), NEI,MECHANISMS OCULAR DIS LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 35 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD DEC 8 PY 1993 VL 1203 IS 2 BP 251 EP 259 DI 10.1016/0167-4838(93)90091-5 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MP543 UT WOS:A1993MP54300012 PM 8268208 ER PT J AU MAENO, M XUE, Y WOOD, TI ONG, RC KUNG, HF AF MAENO, M XUE, Y WOOD, TI ONG, RC KUNG, HF TI CLONING AND EXPRESSION OF CDNA-ENCODING XENOPUS-LAEVIS BONE MORPHOGENETIC PROTEIN-1 DURING EARLY EMBRYONIC-DEVELOPMENT SO GENE LA English DT Note DE NUCLEOTIDE SEQUENCE; GROWTH FACTORS; ECTOPIC CARTILAGE; TADPOLE; CDNA LIBRARY ID VENTRALIZING FACTOR; MESODERM INDUCTION AB The Xenopus laevis DNA fragment encoding a protein homologous with human bone morphogenetic protein-1 (BMP-1) was amplified by polymerase chain reaction (PCR) from cDNA derived from stage 26 (st.26) embryonic RNA. Subsequently this fragment was used as a probe to isolate cDNA clones by screening of a X. laevis st.24 embryonic cDNA library. Two partial clones (22 and 63) were obtained and the missing 5'-end of the clone 22 was extended by the anchored PCR technique. The nucleotide sequence of the resulting clone (22AN) contained an open reading frame coding for a protein with 707 deduced amino acids. Three sizes of mRNA (2.9, 5.2 and 6.6 kb) were detected in blastula (st.9) and early gastrula (st.10) embryos, and in hatched tadpole (st.40), but little or no expression was observed in morula (st.7) and late gastrula (st.12) embryos, suggesting a physiological role(s) of X. laevis BMP-1 in normal embryonic development. RP MAENO, M (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,FREDERICK,MD 21702, USA. NR 17 TC 39 Z9 41 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD DEC 8 PY 1993 VL 134 IS 2 BP 257 EP 261 DI 10.1016/0378-1119(93)90103-A PG 5 WC Genetics & Heredity SC Genetics & Heredity GA MM727 UT WOS:A1993MM72700016 PM 8262384 ER PT J AU MOORE, RC OKA, T AF MOORE, RC OKA, T TI CLONING AND SEQUENCING OF THE CDNA-ENCODING THE MURINE MAMMARY-GLAND LONG-FORM PROLACTIN RECEPTOR SO GENE LA English DT Note DE MUS MUSCULUS; LAMBDA PHAGE LIBRARY; RT-PCR; RECOMBINANT DNA ID MOLECULAR-CLONING; IDENTIFICATION; EXPRESSION; LIVER AB The nucleotide sequence of a 1992-bp cDNA encoding the long form of the murine mammary prolactin receptor (PRL-R) has been determined. The deduced 68-kDa protein has high sequence identity with long forms of prolactin receptors from rat ovary and rabbit mammary gland. C1 NIDDKD,MOLEC & CELLULAR BIOL LAB,BETHESDA,MD 20892. NR 11 TC 25 Z9 29 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD DEC 8 PY 1993 VL 134 IS 2 BP 263 EP 265 DI 10.1016/0378-1119(93)90104-B PG 3 WC Genetics & Heredity SC Genetics & Heredity GA MM727 UT WOS:A1993MM72700017 PM 8262385 ER PT J AU ROSENTHAL, NE AF ROSENTHAL, NE TI DIAGNOSIS AND TREATMENT OF SEASONAL AFFECTIVE-DISORDER SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Discussion ID BRIGHT LIGHT THERAPY; WINTER DEPRESSION; PATTERNS; MOOD RP ROSENTHAL, NE (reprint author), NIMH,CLIN PSYCHOL BRANCH,ENVIRONM PSYCHIAT SECT,BLDG 10,ROOM 4S-239,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 44 TC 45 Z9 45 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 8 PY 1993 VL 270 IS 22 BP 2717 EP 2720 DI 10.1001/jama.270.22.2717 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA MJ821 UT WOS:A1993MJ82100032 PM 8133590 ER PT J AU GOEL, R BEARD, WA KUMAR, A CASASFINET, JR STRUB, MP STAHL, SJ LEWIS, MS BEBENEK, K BECERRA, SP KUNKEL, TA WILSON, SH AF GOEL, R BEARD, WA KUMAR, A CASASFINET, JR STRUB, MP STAHL, SJ LEWIS, MS BEBENEK, K BECERRA, SP KUNKEL, TA WILSON, SH TI STRUCTURE-FUNCTION STUDIES OF HIV-1(1) REVERSE-TRANSCRIPTASE - DIMERIZATION-DEFECTIVE MUTANT L289K SO BIOCHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; SITE-DIRECTED MUTAGENESIS; DEPENDENT DNA POLYMERASE; MONOCLONAL-ANTIBODIES; PRIMER BINDING; ACTIVE-SITE; HTLV-III; AIDS; IDENTIFICATION; HETERODIMER AB Virion-derived HIV-1 reverse transcriptase (RT) has subunits of molecular mass 66 and 51 kDa (p66 and p51, respectively) in an approximately 1:1 ratio. Since enzyme activity appears to depend on dimerization of these subunits, identification of critical regions of primary sequence required for proper dimerization could lead to potential targets for antiviral therapy. A central region of primary sequence contains a leucine hepta-repeat motif from leucine 282 to leucine 310 that has been suggested to be involved in dimerization [Baillon, J. G., Nashed, N. T., Kumar, A., Wilson, S. H., & Jerina, D. M. (1991) New Biol. 3, 1015-1019]. A region including this hepta-repeat was recently shown to be involved in protein-protein interactions required for dimerization [Becerra, S. P., Kumar, A., Lewis, M. S., Widen, S. G., Abbotts, J., Karawya, E. M., Hughes, S. H., Shiloach, J., & Wilson, S. H. (1991) Biochemistry 30, 11708-11719]. To investigate the role of this repeat motif in dimerization, we performed site-directed mutagenesis of these leucine residues from position 282 to position 310. Mutations were introduced in to p66 and p51 RT coding sequences, and the individually purified RT subunit polypeptides were compared with wild-type polypeptides for dimerization. Physical characterization of the purified mutant peptides was conducted by circular dichroism analysis. Binding between p66 and p51 was studied by gel filtration, ultracentrifugation, and CD analysis. L289K-p66 was unable to dimerize with itself and wild-type or L289K-p51. The leucine repeat motif in the p66 subunit appears to be critical in formation of the heterodimer. Conversely, our observation that the wild-type p66 and L289K-p51 can heterodimerize indicates that this leucine residue in p51 is probably not at a hydrophobic protein-protein interface of the heterodimer. These results for subunit dimerization with wild-type and mutant polypeptides were consistent with DNA polymerase activity being dependent on dimerization. C1 NCI, BIOCHEM LAB, BETHESDA, MD 20892 USA. UNIV TEXAS, MED BRANCH, SEALY CTR MOLEC SCI, GALVESTON, TX 77555 USA. NIH, NATL CTR RES RESOURCES, BIOMED ENGN & INSTRUMENTAT PROGRAM, BETHESDA, MD 20892 USA. NIH, OFF DIRECTOR, PROT EXPRESS LAB, BETHESDA, MD 20892 USA. NIEHS, MOLEC GENET LAB, RES TRIANGLE PK, NC 27709 USA. NCI, FREDERICK CANC RES & DEV CTR, PROGRAM RESOURCES INC, STRUCT BIOCHEM LAB, FREDERICK, MD 21702 USA. NR 29 TC 36 Z9 36 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 7 PY 1993 VL 32 IS 48 BP 13012 EP 13018 DI 10.1021/bi00211a009 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MK965 UT WOS:A1993MK96500009 PM 7694651 ER PT J AU WOLFF, J KNIPLING, L AF WOLFF, J KNIPLING, L TI ANTIMICROTUBULE PROPERTIES OF BENZOPHENANTHRIDINE ALKALOIDS SO BIOCHEMISTRY LA English DT Article ID TUBULIN; COLCHICINE; INHIBITION; BINDING; PODOPHYLLOTOXIN; SANGUINARINE; FLUORESCENCE; MICROTUBULES; MECHANISM; INVITRO AB Chelidonine, sanguinarine, and chelerythrine are natural benzophenanthridine alkaloids that inhibit taxol-mediated polymerization of rat brain tubulin in the micromolar range. Chelidonine is a weak, competitive inhibitor of colchicine binding to tubulin but does not inhibit podophyllotoxin binding. On the other hand, sanguinarine inhibits both colchicine and podophyllotoxin binding to tubulin with I50 values of 32 and 46 muM, respectively, and chelerythrine inhibits with I50 values of 55 and 60 muM, respectively. The inhibition by these two agents is of the mixed type. Tubulin forms an acid-reversible pseudobase with the imminium ion of sanguinarine, probably through several of its sulfhydryl groups, as shown by the loss of the yellow color of sanguinarine and its 596-nm fluorescence emission peak. Chelidonine, on the other hand, cannot undergo such pseudobase formation, and we conclude that it acts by a different mechanism. A number of previously described pharmacologic effects of these agents may be due to their inhibition of microtubule function. RP WOLFF, J (reprint author), NIDDKD,BIOCHEM PHARMACOL LAB,BETHESDA,MD 20892, USA. NR 32 TC 111 Z9 115 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 7 PY 1993 VL 32 IS 48 BP 13334 EP 13339 DI 10.1021/bi00211a047 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MK965 UT WOS:A1993MK96500047 PM 7902132 ER PT J AU ANDREWS, AM MURPHY, DL AF ANDREWS, AM MURPHY, DL TI FLUOXETINE AND DESIPRAMINE SELECTIVELY ATTENUATE 2'-NH2-MPTP-INDUCED DEPLETIONS IN SEROTONIN AND NOREPINEPHRINE SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE MPTP (1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE); MPTP ANALOG; MPTP DERIVATIVE; 5-HT(5-HYDROXYTRYPTAMINE, SEROTONIN); NOREPINEPHRINE; FLUOXETINE; DESIPRAMINE ID 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MPTP; INDUCED HYPERTHERMIA; UPTAKE INHIBITORS; BRAIN-SEROTONIN; RAT-BRAIN; NEUROTOXICITY; NEURONS; 5-HYDROXYTRYPTAMINE; METABOLITE; DOPAMINE AB We recently reported that the novel MPTP analog 1-methyl-4-(2'-aminophenyl)-1,2,3,6-tetrahydropyridine (2'-NH2-MPTP) administered to C57BL/6 mice produced substantial decreases in forebrain serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and norepinephrine, with negligible effects on brain dopamine or dopamine metabolites. In the present report, we confirm and extend our original results to include dose-response data and the effect of selective uptake inhibition on the levels of monoamine neurotransmitters in various regions of the mouse brain following treatment with 2'-NH2-MPTP. In a dose-ranging study, 2'-NH2-MPTP (10 mg/kg X 4) produced a 25-30% reduction in frontal cortex 5-HT, 5-HIAA, and norepinephrine. When 4 x 20 mg/kg 2'-NH2-MPTP was administered, 70-75% reductions in 5-HT, 5-HIAA, and norepinephrine in both frontal cortex and hippocampus were seen 1 week after treatment. No changes in dopamine were found in striatum or in any of the other brain regions examined at either dose. Doses of 40 and 60 mg/kg were lethal shortly after a single injection. In mice receiving either fluoxetine or desipramine (10 mg/kg) prior to 2'-NH2-MPTP (20 mg/kg x 4), decreases in 5-HT and norepinephrine, respectively, were significantly attenuated by approximately 30-40%. These data suggest that 2'-NH2-MPTP acts in a dose-dependent manner and that the serotonergic and noradrenergic uptake systems are involved in the mechanism by which 2'-NH2-MPTP causes selective deficits in cortical and hippocampal 5-HT and norepinephrine. C1 AMERICAN UNIV,DEPT CHEM,WASHINGTON,DC 20016. RP ANDREWS, AM (reprint author), NIMH,CLIN SCI LAB,BLDG 10,ROOM 3D41,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Andrews, Anne/B-4442-2011 OI Andrews, Anne/0000-0002-1961-4833 NR 28 TC 11 Z9 11 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 DEC 7 PY 1993 VL 250 IS 2 BP 215 EP 221 DI 10.1016/0014-2999(93)90384-T PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ML715 UT WOS:A1993ML71500001 PM 8112382 ER PT J AU WEISSMAN, AD MCCANN, DJ LORDEN, JF SU, TP AF WEISSMAN, AD MCCANN, DJ LORDEN, JF SU, TP TI AN ABSENCE OF CHANGES IN SIGMA-RECEPTOR SUBTYPES IN THE BRAINS OF GENETICALLY DYSTONIC (DT) RATS SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Note DE DTG (DI-O-TOLLYLGUANIDINE); SKF10047; SIGMA RECEPTOR; RED NUCLEUS; N-ALLYLNORMETAZOCINE; MOVEMENT DISORDER; DYSTONIA ID SYSTEMS AB Binding sites for the sigma ligand [H-3]di-o-tollylguanidine ([H-3]DTG) have been reported to be altered in the brains of genetically dystonic rats. In the present study, selective sigma1 and sigma2 assay conditions were utilized in an effort to define which subpopulation of [H-3]DTG binding sites is altered in the dystonic strain (dt). Both this approach and a re-examination using conditions similar to the previous report failed to confirm a difference between the brains of dystonic and normal rats in terms of sigma binding. Although not directly negating the possible involvement of sigma receptors in dystonia, these results indicate that sigma1 and sigma2 receptors appear unchanged in dystonic rats. C1 NATL INST DRUG ABUSE,ADDICT RES CTR,NEUROSCI BRANCH,NEUROIMAGING & DRUG ACT SECT,BALTIMORE,MD 21224. UNIV ALABAMA,DEPT PSYCHOL,BIRMINGHAM,AL 35294. NR 12 TC 4 Z9 5 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 DEC 7 PY 1993 VL 250 IS 2 BP 329 EP 332 DI 10.1016/0014-2999(93)90399-3 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ML715 UT WOS:A1993ML71500016 PM 8112390 ER PT J AU ZOLKIEWSKA, A MOSS, J AF ZOLKIEWSKA, A MOSS, J TI INTEGRIN-ALPHA-7 AS SUBSTRATE FOR A GLYCOSYLPHOSPHATIDYLINOSITOL-ANCHORED ADP-RIBOSYLTRANSFERASE ON THE SURFACE OF SKELETAL-MUSCLE CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID RIBOSYLATION; PROTEINS; BINDING; INTEGRINS; ADHESION; LAMININ; ADULT AB An arginine-specific mono-ADP-ribosyltransferase is expressed on the surface of differentiated mouse skeletal muscle cells and is anchored in the membrane via a glycosylphosphatidylinositol tail. Following incubation of intact cells with [adenylate-P-32]NAD and analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), a 97-kDa [P-32]ADP-ribosylated protein was observed under reducing conditions and a 140-kDa complex under nonreducing conditions. The ADP-ribosylated protein was purified on a laminin affinity column. Based on its N-terminal sequence (FNLDVMGAIRKEGEPGSLFGF) and a partial internal sequence (GLMRSEELSFVAGAP), the modified protein was identified as integrin alpha7. Following partial trypsin digestion, a 39-kDa/79-kDa radiolabeled fragment was produced (reduced/nonreduced SDS-PAGE), narrowing the ADP-ribosylation site to a 39-kDa segment in the extracellular domain of integrin alpha7. Labeling under optimal conditions was at least 0.4 mol of ADP-ribose/mol of integrin alpha7. Selective expression of both ADP-ribosyltransferase and integrin alpha7 in cardiac and skeletal muscle, a similar developmental appearance, and the apparently specific ADP-ribosylation, are consistent with a regulatory association between these proteins. ADP-ribosylation may modulate integrin receptor signaling and could play a significant role in the regulation of muscle cell function by the extracellular matrix. RP ZOLKIEWSKA, A (reprint author), NHLBI,CELLULAR METAB LAB,BLDG 10,RM 5N307,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 21 TC 126 Z9 127 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 5 PY 1993 VL 268 IS 34 BP 25273 EP 25276 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MK100 UT WOS:A1993MK10000004 PM 8244957 ER PT J AU SKOWYRA, D WICKNER, S AF SKOWYRA, D WICKNER, S TI THE INTERPLAY OF THE GRPE HEAT-SHOCK PROTEIN AND MG2+ IN REPA MONOMERIZATION BY DNAJ AND DNAK SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SPECIALIZED NUCLEOPROTEIN STRUCTURES; ESCHERICHIA-COLI DNAJ; F PLASMID REPLICATION; BACTERIOPHAGE-LAMBDA; CELLULAR DEFECTS; GENE GROPC; INITIATION; CHAPERONE; ORIGIN; MUTANTS AB Genetic and biochemical studies have established that the sole function of the Escherichia coli DnaJ, DnaK, and GrpE heat shock proteins in plasmid P1 DNA replication is to convert RepA dimers to monomers. Monomers bind avidly to oriP1 DNA and initiate DNA replication. However, with purified heat shock proteins, only DnaJ, DnaK, and ATP were required for the monomerization of RepA; GrpE was not required. We have found reaction conditions that mimic the physiological situation. GrpE function is absolutely necessary for RepA activation in vitro with DnaJ and DnaK when the free Mg2+ concentration is maintained at a level of approximately 1 muM by a metal ion buffer system. EDTA or physiological metabolites, including citrate, phosphate, pyrophosphate, and ATP, all elicit the GrpE requirement. With these metal ion-buffering systems, GrpE specifically lowers the concentration of Mg2+ required for the RepA activation reaction. The absence of Mg2+ blocks activation and high levels of Mg2+ in solution bypass the requirement for GrpE but not for the other two heat shock proteins. Our results imply that GrpE facilitates the utilization of Mg2+ for an essential step in RepA activation. C1 NCI,MOLEC BIOL LAB,BLDG 37,RM 2D19,BETHESDA,MD 20892. NR 37 TC 29 Z9 29 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 5 PY 1993 VL 268 IS 34 BP 25296 EP 25301 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MK100 UT WOS:A1993MK10000007 PM 8244960 ER PT J AU GAO, JL MURPHY, PM AF GAO, JL MURPHY, PM TI SPECIES AND SUBTYPE VARIANTS OF THE N-FORMYL PEPTIDE CHEMOTACTIC RECEPTOR REVEAL MULTIPLE IMPORTANT FUNCTIONAL DOMAINS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID XENOPUS OOCYTES REQUIRES; INTERLEUKIN-8 RECEPTOR; EXPRESSION; CLONING; CDNA; AFFINITY AB The N-formyl peptide receptor (FPR) is a seven transmembrane-domain receptor that mediates trafficking and activation of phagocytic leukocytes in response to N-formyl oligopeptides such as fMet-Leu-Phe. cDNAs for high affinity FPRs have been cloned from both human (huFPR) and rabbit (rabFPR). To identify functional domains of FPR, we have studied two structurally related ''natural mutants'' that are 100-10,000-fold less sensitive than huFPR and rabFPR to fMet-Leu-Phe owing to sequence differences that are located predominantly in the proposed extracellular and transmembrane domains. The first is murine FPR (muFPR, 76% identical to huFPR) whose gene we have now cloned and expressed in Xenopus oocytes; the second is the previously reported human FPR-like 1 receptor (FPRL1R, 69% identical to huFPR) which was used to construct huFPR-FPRL1R chimeras. Comparison of the structure and function of huFPR, FPRL1R, muFPR, rabFPR, and huFPR-FPRL1R chimeras suggests that multiple non-contiguous residues must be apposed by coordinate folding of all of the extracellular and transmembrane domains in order to form the high affinity fMLF-binding site. C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. NR 36 TC 106 Z9 107 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 DEC 5 PY 1993 VL 268 IS 34 BP 25395 EP 25401 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MK100 UT WOS:A1993MK10000021 PM 8244972 ER PT J AU TANIZAWA, A BERTRAND, R KOHLHAGEN, G TABUCHI, A JENKINS, J POMMIER, Y AF TANIZAWA, A BERTRAND, R KOHLHAGEN, G TABUCHI, A JENKINS, J POMMIER, Y TI CLONING OF CHINESE-HAMSTER DNA TOPOISOMERASE-I CDNA AND IDENTIFICATION OF A SINGLE-POINT MUTATION RESPONSIBLE FOR CAMPTOTHECIN RESISTANCE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-LINE; LUNG-CANCER; DC3F CELLS; GENE; SEQUENCE; BINDING; MECHANISM; REPLICATION; INHIBITION; COVALENT AB A camptothecin-resistant (DC3F/C-10) Chinese hamster cell line that contains a catalytically altered and camptothecin (CPT)-resistant DNA topoisomerase I (top 1) (Tanizawa, A., and Pommier, Y. (1992) Cancer Res. 52, 1848-1854) and the parent cell line (DC3F) were used to compare top 1 mRNAs and cDNAs. Northern blot analysis showed a single 4.1-kilobase band without quantitative reduction between the two cell lines. We have cloned and sequenced top 1 cDNAs. DC3F and DC3F/C-10 top 1 c-DNA are 3591 and 3626 base pair long, respectively, and encode 767 amino acids. The homology of deduced amino acid sequences between Chinese hamster and mouse or human top 1 are 98.1 and 96.7, respectively. cDNAs from DC3F/C-10 and DC3F cells differ by a single base point mutation (G to A) which results in an amino acid change from Gly505 to Ser (Gly505 --> Ser). G505 corresponds to Gly503 of human top 1 cDNA and is located 220 amino acids away from the presumed catalytic Tyr725. The point mutation in the Chinese hamster top 1 is located in a region that is highly conserved among all cloned top 1 cDNAs (plant ATH, vaccinia virus, Shope fibroma virus, Drosophila, Saccharomyces cerevisiae, Schizosaccharomyces pombe, mouse, and Human). A mutation of Asp533 to Gly in this same region has been shown to confer CPT resistance for human top 1. Chinese hamster top 1 protein with a Gly505 --> Ser mutation that was expressed in bacteria was resistant to CPT, indicating that this single base mutation is involved in CPT resistance. Our results suggest that the highly conserved region around Gly505 plays an important role in the interactions among top 1, DNA, and CPT. C1 NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,BLDG 37,RM 5C25,BETHESDA,MD 20892. NR 39 TC 88 Z9 89 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 5 PY 1993 VL 268 IS 34 BP 25463 EP 25468 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MK100 UT WOS:A1993MK10000030 PM 8244980 ER PT J AU AROCA, P URABE, K KOBAYASHI, T TSUKAMOTO, K HEARING, VJ AF AROCA, P URABE, K KOBAYASHI, T TSUKAMOTO, K HEARING, VJ TI MELANIN BIOSYNTHESIS PATTERNS FOLLOWING HORMONAL-STIMULATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CULTURED HUMAN MELANOCYTES; HAIR FOLLICULAR MELANOCYTES; TYROSINASE MESSAGE LEVEL; MAMMALIAN TYROSINASE; DOPACHROME OXIDOREDUCTASE; CONTROL POINT; METAL-IONS; CELL-LINE; MELANOGENESIS; MOUSE AB The effect of melanocyte-stimulating hormone (MSH) on the differentiation of mammalian melanocytes has been widely studied since the early 1950s. There have been many reports about the stimulatory effect of MSH on melanin production and specifically on the activity of tyrosinase, the critical enzyme in the melanogenic pathway. However, few and variable results have been obtained concerning the effect of this hormone on the regulation of DOPAchrome tautomerase (TRP2), another melanogenic enzyme which functions later in the melanogenic pathway, or on other melanogenic activities, such as TRP1. In this study, we show that the MSH-induced stimulation of tyrosinase is accompanied by no significant change in the synthesis or catalytic activities of other melanogenic enzymes such as TRP1 or TRP2. This in turn elicits a dramatic increase in melanin production accompanied by a significant decrease in the incorporation of carboxylated precursors into that melanin biopolymer, although the biological implication of that is still unclear. C1 NCI,CELL BIOL LAB,BLDG 37,RM 1B22,BETHESDA,MD 20892. YAMANASHI MED UNIV,DEPT DERMATOL,YAMANASHI 40938,JAPAN. NR 67 TC 83 Z9 86 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 5 PY 1993 VL 268 IS 34 BP 25650 EP 25655 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MK100 UT WOS:A1993MK10000055 PM 7902353 ER PT J AU VOGEL, SS LEIKINA, EA CHERNOMORDIK, LV AF VOGEL, SS LEIKINA, EA CHERNOMORDIK, LV TI LYSOPHOSPHATIDYLCHOLINE REVERSIBLY ARRESTS EXOCYTOSIS AND VIRAL FUSION AT A STAGE BETWEEN TRIGGERING AND MEMBRANE MERGER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SEA-URCHIN EGGS; SQUID GIANT SYNAPSE; INFLUENZA HEMAGGLUTININ; CORTICAL REACTION; VESICLE FUSION; CALCIUM; VIRUS; GRANULES; PH; BACULOVIRUS AB Little is known of the events occurring between membrane fusion triggering and subsequent fusion steps. To dissect this process we applied a reversible inhibitor of membrane fusion, lysophosphatidylcholine, to arrest exocytosis and virus-mediated syncytia formation. Next Ca2+ or H+ (the respective fusion triggers) was administered and later removed. Then, inhibitor was withdrawn and fusion ensued, demonstrating that triggering causes the formation of an ''activated state,'' which later develops into the fused state. Therefore, while different fusion processes utilize different triggers, the pivotal step involving membrane merger is trigger-independent and lipid-sensitive. C1 NICHHD,THEORET & PHYS BIOL LAB,BLDG 10,RM 6C-101,BETHESDA,MD 20892. RI Vogel, Steven/A-3585-2012; OI Vogel, Steven/0000-0002-3005-2667 NR 39 TC 89 Z9 92 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 5 PY 1993 VL 268 IS 34 BP 25764 EP 25768 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MK100 UT WOS:A1993MK10000071 PM 8245012 ER PT J AU MACDONALD, NJ DELAROSA, A BENEDICT, MA FREIJE, JMP KRUTSCH, H STEEG, PS AF MACDONALD, NJ DELAROSA, A BENEDICT, MA FREIJE, JMP KRUTSCH, H STEEG, PS TI A SERINE PHOSPHORYLATION OF NM23, AND NOT ITS NUCLEOSIDE DIPHOSPHATE KINASE-ACTIVITY, CORRELATES WITH SUPPRESSION OF TUMOR METASTATIC POTENTIAL SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ROUS-SARCOMA VIRUS; DUCTAL BREAST CARCINOMAS; 2 CELLULAR PROTEINS; LARGE T-ANTIGEN; WILD-TYPE; SV40-TRANSFORMED CELLS; TRANSFORMING PROTEINS; PROGESTERONE-RECEPTOR; CHEMICAL-PROPERTIES; MYXOCOCCUS-XANTHUS AB We describe a serine phosphorylation of the putative metastasis suppressor protein Nm23, and present evidence of its relevance to the signal transduction and tumor metastatic processes. Nm23 was previously demonstrated to exhibit nucleoside diphosphate kinase (NDPK) activity, which transfers a phosphate among nucleoside tri- and diphosphates via an Nm23-phosphohistidine intermediate. Recent data have dissociated the NDPK activity of Nm23 from its phenotypic effects; therefore we have asked whether Nm23 possesses additional biochemical functions. An acid-stable (nonhistidine) phosphorylation was identified on autophosphorylated purified recombinant Nm23 proteins and [P-32]orthophosphate-labeled human breast carcinoma and murine melanoma Nm23. Phosphoamino acid analysis identified serine as the acid-stable phosphorylation and serine 44 as the major site of phosphorylation. The acid stable phosphorylation (serine) of Nm23 was inhibited by cAMP in vitro and forskolin in vivo, suggesting that this phosphorylation pathway is regulated in signal transduction. No effect of cAMP was observed on Nm223 NDPK activity. Once phosphorylated, Nm23-phosphoserine can release free phosphate in vitro. The biological relevance of the novel phosphorylation identified herein is suggested by the direct correlation of in vivo Nm23 acid-stable phosphorylation levels, but not Nm23 NDPK activity, with suppression of tumor metastatic potential among control and nm23-1 transfected murine melanoma cells. C1 UNIV OVIEDO, DEPT BIOL FUNCT, E-33006 OVIEDO, SPAIN. RP NCI, PATHOL LAB, WOMENS CANC SECT, BLDG 10, RM 2A33, BETHESDA, MD 20892 USA. RI Freije, Jose M.P./A-6535-2008 OI Freije, Jose M.P./0000-0002-4688-8266 NR 97 TC 201 Z9 209 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 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 5 PY 1993 VL 268 IS 34 BP 25780 EP 25789 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MK100 UT WOS:A1993MK10000074 PM 8245015 ER PT J AU PAVLIAK, V NASHED, EM POZSGAY, V KOVAC, P KARPAS, A CHU, CY SCHNEERSON, R ROBBINS, JB GLAUDEMANS, CPJ AF PAVLIAK, V NASHED, EM POZSGAY, V KOVAC, P KARPAS, A CHU, CY SCHNEERSON, R ROBBINS, JB GLAUDEMANS, CPJ TI BINDING OF THE O-ANTIGEN OF SHIGELLA-DYSENTERIAE TYPE-1 AND TYPE-26 RELATED SYNTHETIC FRAGMENTS TO A MONOCLONAL IGM ANTIBODY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STREPTOCOCCUS-PNEUMONIAE; ENTERIC INFECTIONS; RURAL BANGLADESH; POLYSACCHARIDE; LIGANDS; LIPOPOLYSACCHARIDE; SPECIFICITY; DEXTRAN; SHIGELLA-DYSENTERIAE-1; VIRULENCE AB Shigella dysenteriae type 1 possesses an O-antigen whose repeating unit is -->3-alpha-L-Rhap-(1-->3)-alpha-L-Rhap-(1-->2)-alpha-D-Galp-(1-->3)-alpha-D-GlcpNAc-(1-->, where Rhap is rhamnopyranosyl, Galp is galactopyranosyl, and Glcp is glucopyranosyl. Using ligand-induced protein fluorescence change, we have measured the affinities of a monoclonal murine IgM for 26 fragments of, or related to, the structure of the O-polysaccharide and of the IgM Fab for the intact O-specific bacterial polysaccharide. Synthetic saccharides used were methyl glycosides to ensure an anomerically defined pyranosyl ring conformation. The galactosyl residue is the only monosaccharide of the antigenic epitope that shows quantifiable binding: approximately 3.0 kcal/mol of binding free energy, depending on the structure and conformation of the fragment it is a part of. Addition of an alpha-(1-->2)-linked rhamnosyl residue increases the free energy of binding significantly. We propose this rhamnopyranosyl-alpha-(1-->2)-galactopyranosyl disaccharide to be the basic determinant of the Shigella O-polysaccharide. Further extension (by linkages as in the natural antigen) of this oligosaccharidic ligand toward the upstream end (in an oligo- (or poly-)saccharide, such as A-->B-->C-->D-->E-->m, where A, B, C, D, and E are sugars and m is any moiety, such as methyl, we define A as the glycosyl- or upstream terminus, and E as the glycoside- or downstream terminus) by rhamnosyl and N-acetylglucosaminyl moieties improves the binding only minimally. The antibody is quite specific for the rhamnosyl-alpha-(1-->2)-galactosyl sequence but less so for the nature of the attachment to the galactosyl residue on the downstream side. Measurements using IgM Fab and the intact O-specific polysaccharide show that the antibody can bind internal segments on the antigen chain. The free energy of binding of this antibody for the disaccharide determinant varies from -DELTAG of 4.7 to 5.1 kcal/mol, depending on its flanking residues. C1 NIDDKD,BETHESDA,MD 20892. US FDA,CTR BIOL RES & REVIEW,BETHESDA,MD 20892. NICHHD,BETHESDA,MD 20892. NR 60 TC 39 Z9 40 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 5 PY 1993 VL 268 IS 34 BP 25797 EP 25802 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MK100 UT WOS:A1993MK10000076 PM 7503987 ER PT J AU VERONESE, FD REITZ, MS GUPTA, G ROBERTGUROFF, M BOYERTHOMPSON, C LOUIE, A GALLO, RC LUSSO, P AF VERONESE, FD REITZ, MS GUPTA, G ROBERTGUROFF, M BOYERTHOMPSON, C LOUIE, A GALLO, RC LUSSO, P TI LOSS OF A NEUTRALIZING EPITOPE BY A SPONTANEOUS POINT MUTATION IN THE V3 LOOP OF HIV-1 ISOLATED FROM AN INFECTED LABORATORY WORKER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEIN; TRANSMEMBRANE PROTEIN; MONOCLONAL-ANTIBODY; HTLV-III; TYPE-1; DETERMINANT; GENERATION; RESISTANT; PEPTIDES AB The third hypervariable region, or V3 loop, represents the principal neutralizing domain of the gp120 envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1). Sequential viral isolates from a laboratory worker (LW) accidentally infected with HIV-1IIIB in 1985 were analyzed using type-specific neutralizing monoclonal antibodies directed to the V3 loop. A single amino acid substitution, Ala --> Thr at position 21 in the V3 loop of HIV-1LW isolated in 1987, was shown to determine the loss of the neutralizing epitope recognized by one of the monoclonal antibodies (M77). However, this antibody efficiently recognized linear V3 loop peptides containing either the Ala or Thr residue at position 21, indicating that a local change in conformation was responsible for the epitope loss in the native gp120. Molecular modeling studies, experimentally supported by different amino acid replacements at position 21, indicated that the Ala --> Thr substitution leads to a drastic change in the domain of the V3 loop, which contains the complementary surface for antibody binding. These results provide evidence for the first time that a conformation-dependent epitope within the V3 loop of HIV-1 is involved in the generation of neutralization escape mutants in vivo. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. LOS ALAMOS NATL LAB,THEORET BIOL & BIOPHYS GRP,LOS ALAMOS,NM 87545. RP VERONESE, FD (reprint author), ADV BIOSCI LABS INC,DEPT CELL BIOL,KENSINGTON,MD 20895, USA. NR 28 TC 48 Z9 48 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 5 PY 1993 VL 268 IS 34 BP 25894 EP 25901 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MK100 UT WOS:A1993MK10000087 ER PT J AU LEE, SB SHIN, SH HEPLER, JR GILMAN, AG RHEE, SG AF LEE, SB SHIN, SH HEPLER, JR GILMAN, AG RHEE, SG TI ACTIVATION OF PHOSPHOLIPASE C-BETA-2 MUTANTS BY G-PROTEIN ALPHA(Q)-SUBUNIT AND BETA-GAMMA-SUBUNITS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EXPRESSION SYSTEM; ALPHA-SUBUNITS; VACCINIA VIRUS; ISOZYME; PURIFICATION; POLYMERASE; DIVERSITY; SEQUENCE; CLONING; MEMBERS AB The beta- but not the gamma- and delta-type isozymes of inositol phospholipid-specific phospholipase C (PLC) are activated by G protein alpha(q) and betagamma subunits. The beta-type PLC isozymes differ from other isozymes in that they contain a long carboxyl-terminal region downstream of the Y catalytic domain and a region rich in acidic amino acids between the two separated X and Y catalytic domains. To determine the sites on PLC-beta2 that participate in the interaction of the enzyme with alpha(q) and betagamma subunits, we introduced specific truncations and substitutions in the PLC-beta2 cDNA at positions corresponding to the carboxyl-terminal and acidic amino acid-rich regions, respectively. After transient expression of these cDNA clones in CV-1 cells, the mutant enzymes were partially purified and their capacity to be activated by alpha(q) and betagamma subunits determined. Substitution of glutamine residues for three or all seven of a stretch of consecutive glutamic acids in the acidic domain of PLC-beta2 affected neither alpha(q)- nor betagamma-dependent activation significantly. Carboxyl-terminal truncation to residue Gly-934 or to residue Ala-867 resulted in enzymes that were activated by betagamma but not by alpha(q). This result suggests that the carboxyl-terminal region of PLC-beta2 is required for activation by alpha(q) and that betagamma subunits interact with a different region of the enzyme. Thus, alpha(q) and betagamma subunits may independently modulate a single PLC-beta2 molecule concurrently. C1 NHLBI, BIOCHEM LAB, BLDG 3, RM 122, BETHESDA, MD 20892 USA. UNIV TEXAS, SW MED CTR, DEPT PHARMACOL, DALLAS, TX 75235 USA. NR 33 TC 118 Z9 118 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 5 PY 1993 VL 268 IS 34 BP 25952 EP 25957 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MK100 UT WOS:A1993MK10000095 PM 8245028 ER PT J AU CHOYKE, PL GOMES, MN AF CHOYKE, PL GOMES, MN TI SURGERY FOR SMALL ABDOMINAL AORTIC-ANEURYSM SO LANCET LA English DT Editorial Material C1 GEORGETOWN UNIV HOSP,DEPT SURG,WASHINGTON,DC 20007. RP CHOYKE, PL (reprint author), NIH,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892, USA. NR 6 TC 3 Z9 3 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD DEC 4 PY 1993 VL 342 IS 8884 BP 1377 EP 1377 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA MK095 UT WOS:A1993MK09500005 PM 7901677 ER PT J AU LIEBMANN, J COOK, JA MITCHELL, JB AF LIEBMANN, J COOK, JA MITCHELL, JB TI CREMOPHOR-EL, SOLVENT FOR PACLITAXEL, AND TOXICITY SO LANCET LA English DT Letter RP LIEBMANN, J (reprint author), NCI,RADIAT BIOL BRANCH,BETHESDA,MD 20892, USA. NR 6 TC 50 Z9 52 U1 0 U2 4 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD DEC 4 PY 1993 VL 342 IS 8884 BP 1428 EP 1428 DI 10.1016/0140-6736(93)92789-V PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA MK095 UT WOS:A1993MK09500048 PM 7901713 ER PT J AU TASSANEEYAKUL, W VERONESE, ME BIRKETT, DJ GONZALEZ, FJ MINERS, JO AF TASSANEEYAKUL, W VERONESE, ME BIRKETT, DJ GONZALEZ, FJ MINERS, JO TI VALIDATION OF 4-NITROPHENOL AS AN IN-VITRO SUBSTRATE PROBE FOR HUMAN LIVER CYP2E1 USING CDNA EXPRESSION AND MICROSOMAL KINETIC TECHNIQUES SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID ETHANOL-INDUCIBLE CYTOCHROME-P-450; PARA-NITROPHENOL; RAT-LIVER; IMMUNOCHEMICAL EVIDENCE; REDUCTIVE METABOLISM; BENZENE METABOLISM; ISOZYME 3A; OXIDATION; INDUCTION; HYDROXYLATION AB The involvement of human cytochrome P450 (CYP) 2E1 in the hydroxylation of 4-nitrophenol (4NP) to 4-nitrocatechol (4NC) has been investigated using cDNA expression and liver microsomal kinetic and inhibitor techniques. 4NP hydroxylation by human liver microsomes and cDNA-expressed human CYP2E1 exhibited Michaelis-Menten kinetics; the respective apparent K-m values were 30 +/- 7 and 21 mu M. Mutual competitive inhibition was observed for 4NP and chlorzoxazone (CZ) (an alternative human CYP2E1 substrate) in liver microsomes, with close similarities between the calculated apparent K-m and K-i values for each individual compound. 4NP and CZ hydroxylase activities in microsomes from 18 liver donors varied to a similar extent (3.3- and 3.0-fold, respectively) and 4NP hydroxylase activity correlated significantly (r(s) greater than or equal to 0.75, P < 0.005) with both CZ hydroxylation and immunoreactive CYP2E1 content. The prototypic CYP2E1 inhibitor, diethyldithiocarbamate, was a potent inhibitor of 4NC formation and decreased 4NP hydroxylation by cDNA-expressed CYP2E1 and human liver microsomes in parallel. Probes for other human CYP isoforms namely (alpha-naphthoflavone, coumarin, sulphaphenazole, quinidine, troleandomycin and mephenytoin) caused <15% inhibition of liver microsomal 4NP hydroxylation. These data confirm that, as in animal species, 4NP hydroxylation is catalysed largely by CYP2E1 in human liver and 4NP may therefore be used as an in vitro substrate probe for the human enzyme. C1 FLINDERS MED CTR,DEPT CLIN PHARMACOL,ADELAIDE,SA 5042,AUSTRALIA. NIH,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 52 TC 120 Z9 125 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD DEC 3 PY 1993 VL 46 IS 11 BP 1975 EP 1981 DI 10.1016/0006-2952(93)90639-E PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MM435 UT WOS:A1993MM43500013 PM 8267647 ER PT J AU ICHIKAWA, H MITANI, S HIJIYA, H NAKAGO, T JACOBOWITZ, DM SUGIMOTO, T AF ICHIKAWA, H MITANI, S HIJIYA, H NAKAGO, T JACOBOWITZ, DM SUGIMOTO, T TI CALRETININ-IMMUNOREACTIVITY IN TRIGEMINAL NEURONS INNERVATING THE NASAL-MUCOSA OF THE RAT SO BRAIN RESEARCH LA English DT Article DE CALRETININ; TACHYKININ; NASAL MUCOSA; CORNEA; TRIGEMINAL GANGLION; RAT ID CARBONIC-ANHYDRASE ACTIVITY; CALCIUM-BINDING PROTEIN; PRIMARY AFFERENT NEURONS; DORSAL-ROOT GANGLIA; PERIPHERAL NERVOUS-SYSTEM; PRIMARY SENSORY NEURONS; SUBSTANCE-P; HORSERADISH-PEROXIDASE; CENTRAL PROJECTIONS; IMMUNOHISTOCHEMICAL LOCALIZATION AB Trigeminal primary neuronal cell bodies were labeled by retrograde transport of Fluoro-gold (FG) from the nasal mucosa of rats. The trigeminal ganglion containing the labeled cell bodies were processed for double stain for calretinin- and tachykinin-immunoreactivities (CR- and TK-irs). Except for a few contralateral cells, all the cells that innervated the nasal mucosa (NM cells) were confined to the ophthalmo-maxillary division of the trigeminal ganglion ipsilateral to the FG application. In the dorsal two-thirds of the ganglion, NM cells formed a cluster in the rostromedial part of ophthalmo-maxillary division (the rostromedial cluster). In the ventral third, the number of cells in the rostromedial cluster markedly decreased. Instead, numerous NM cells were found in the caudolateral part of the ophthalmo-maxillary division (the caudoventrolateral cluster). CR- and TK-irs were detected in 18% and 54% of overall population of NM cells, respectively. Virtually all of CR-immunoreactive (-ir) NM cells coexpressed TK. Although the proportion of TK-ir cells, irrespective of CR-ir, was similar for both clusters, CR-ir cells were more frequent in the caudoventrolateral cluster than in the rostromedial cluster. In the dorsal 1/3 of the ganglion where all the NM cells belonged to the rostromedial cluster, only 8.4% exhibited CR-ir. On the other hand, as much as 30.1% of NM cells expressed CR-ir in the ventral 1/3 where most NM cells were found in the caudoventrolateral cluster. Trigeminal cell bodies innervating the cornea and conjunctivum were located in the rostromedial part of the ophthalmo-maxillary division. About 40% and 4% of them were positive for TK and CR, respectively. As was the case for NM cells, all the CR-ir cells innervating these (peri-)ocular structures exhibited TK-ir. The nasal mucosa contained both CR- and TK-ir free nerve endings within the epithelium. The CR-ir endings almost always coexpressed TK. C1 OKAYAMA UNIV, SCH DENT, DEPT ORAL ANAT 2, OKAYAMA, OKAYAMA 700, JAPAN. OKAYAMA UNIV, SCH DENT, DEPT ORTHODONT, OKAYAMA, OKAYAMA, JAPAN. NIMH, CLIN SCI LAB, BETHESDA, MD 20892 USA. NR 51 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD DEC 3 PY 1993 VL 629 IS 2 BP 231 EP 238 DI 10.1016/0006-8993(93)91325-M PG 8 WC Neurosciences SC Neurosciences & Neurology GA MJ732 UT WOS:A1993MJ73200007 PM 8111627 ER PT J AU DOMBROWICZ, D FLAMAND, V BRIGMAN, KK KOLLER, BH KINET, JP AF DOMBROWICZ, D FLAMAND, V BRIGMAN, KK KOLLER, BH KINET, JP TI ABOLITION OF ANAPHYLAXIS BY TARGETED DISRUPTION OF THE HIGH-AFFINITY IMMUNOGLOBULIN-E RECEPTOR ALPHA-CHAIN GENE SO CELL LA English DT Article ID FC-EPSILON-RI; MOUSE MAST-CELLS; IMMEDIATE HYPERSENSITIVITY REACTIONS; EPIDERMAL LANGERHANS CELLS; IGE RECEPTOR; SURFACE EXPRESSION; TRANSFECTED CELLS; BONE-MARROW; RESISTANCE; MICE AB Mast cells and basophils, which are activated by immunoglobulin E (IgE) and allergen, play a prominent role in anaphylaxis. However, they express at least three types of IgE receptor, including the high affinity IgE receptor (FcepsilonRI). The relative contribution of these IgE receptors, and possibly other receptors such as FcepsilonRII/CD23 and Mac-2, to the genesis of in vivo anaphylaxis is still unclear. To address this question, we have generated FcepsilonRI-deficient mice. These mice appear normal and express a normal number of mast cells, but they are resistant to cutaneous and systemic anaphylaxis. These data demonstrate that FcepsilonRI is necessary for the initiation of IgE-dependent anaphylactic reactions. Therefore, interfering with its function should be an effective means of treating allergy, regardless of the allergen specificity. C1 UNIV N CAROLINA,DEPT MED,CHAPEL HILL,NC 27599. RP DOMBROWICZ, D (reprint author), NIAID,MOLEC ALLERGY & IMMUNOL SECT,ROCKVILLE,MD 20852, USA. RI Dombrowicz, David/F-7044-2013 OI Dombrowicz, David/0000-0002-0485-8923 FU NIDDK NIH HHS [R01 DK 46003-01] NR 43 TC 272 Z9 275 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD DEC 3 PY 1993 VL 75 IS 5 BP 969 EP 976 DI 10.1016/0092-8674(93)90540-7 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MK966 UT WOS:A1993MK96600016 PM 8252632 ER PT J AU FISHEL, R LESCOE, MK RAO, MRS COPELAND, NG JENKINS, NA GARBER, J KANE, M KOLODNER, R AF FISHEL, R LESCOE, MK RAO, MRS COPELAND, NG JENKINS, NA GARBER, J KANE, M KOLODNER, R TI THE HUMAN MUTATOR GENE HOMOLOG MSH2 AND ITS ASSOCIATION WITH HEREDITARY NONPOLYPOSIS COLON-CANCER SO CELL LA English DT Article ID DNA MISMATCH CORRECTION; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; HUMAN-CELLS; COLORECTAL-CANCER; NUCLEAR EXTRACTS; G.T MISPAIRS; REPAIR; CONVERSION; PROTEIN AB We have identified a human homolog of the bacterial MutS and S. cerevisiae MSH proteins, called hMSH2. Expression of hMSH2 in E. coli causes a dominant mutator phenotype, suggesting that hMSH2, like other divergent MutS homologs, interferes with the normal bacterial mismatch repair pathway. hMSH2 maps to human chromosome 2p22-21 near a locus implicated in hereditary nonpolyposis colon cancer (HNPCC). A T to C transition mutation has been detected in the -6 position of a splice acceptor site in sporadic colon tumors and in affected individuals of two small HNPCC kindreds. These data and reports indicating that S. cerevisiae msh2 mutations cause an instability of dinucleotide repeats like those associated with HNPCC suggest that hMSH2 is the HNPCC gene. C1 NCI, FREDERICK CANC RES & DEV CTR,ADV BIOSCI LABS, BASIC RES PROGRAM,MAMMALIAN GENET LAB, FREDERICK, MD 21702 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV CANC EPIDEMIOL & CONTROL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV CELLULAR & MOLEC BIOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT BIOL CHEM & MOLEC PHARMACOL, BOSTON, MA 02115 USA. RP UNIV VERMONT, SCH MED, MARKEY CTR MOLEC GENET, DEPT MICROBIOL & MOLEC GENET, BURLINGTON, VT 05405 USA. FU NCI NIH HHS [CA56542]; NHGRI NIH HHS [HG00305]; NIGMS NIH HHS [GM50006] NR 70 TC 2266 Z9 2309 U1 8 U2 167 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD DEC 3 PY 1993 VL 75 IS 5 BP 1027 EP 1038 DI 10.1016/0092-8674(93)90546-3 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MK966 UT WOS:A1993MK96600022 PM 8252616 ER PT J AU MORSE, RH AF MORSE, RH TI NUCLEOSOME DISRUPTION BY TRANSCRIPTION FACTOR-BINDING IN YEAST SO SCIENCE LA English DT Article ID RNA POLYMERASE-II; TUMOR VIRUS PROMOTER; DNA-BINDING; POSITIONED NUCLEOSOMES; SACCHAROMYCES-CEREVISIAE; REGULATORY PROTEINS; CHROMATIN STRUCTURE; PHO5 PROMOTER; MAJOR LATE; GENE AB Studies in vivo and in vitro have shown that the packaging of DNA into chromatin can affect gene expression. Here, binding of the yeast transcriptional activator GAL4 to DNA in chromatin has been investigated in vivo with a yeast episome. A positioned nucleosome that is present in cells grown in glucose and contains a single GAL4 binding site is disrupted by GAL4 binding in galactose. GAL4 can also bind to DNA in chromatin when the carboxyl-terminal activation domain of GAL4 is either masked by GAL80 or is absent. These results show that a transcription factor can bind to its site in vivo in what would appear to be a repressive chromatin structure. C1 NIDDKD,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892. OI Morse, Randall/0000-0003-0000-8718 NR 56 TC 63 Z9 63 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 3 PY 1993 VL 262 IS 5139 BP 1563 EP 1566 DI 10.1126/science.8248805 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MK329 UT WOS:A1993MK32900038 PM 8248805 ER PT J AU ARIDOR, M RAJMILEVICH, G BEAVEN, MA SAGIEISENBERG, R AF ARIDOR, M RAJMILEVICH, G BEAVEN, MA SAGIEISENBERG, R TI ACTIVATION OF EXOCYTOSIS BY THE HETEROTRIMERIC-G PROTEIN-G(I3) SO SCIENCE LA English DT Article ID RAT MAST-CELLS; GTP-BINDING PROTEINS; SYNTHETIC PEPTIDES; ALPHA-SUBUNIT; SUBSTANCE-P; MASTOPARAN; IDENTIFICATION; NUCLEOTIDE; SECRETION; MEMBRANES AB Secretagogues of rat peritoneal mast cells, such as mastoparan and compound 48/80, induce mast cell exocytosis by activating directly the guanosine triphosphate-binding proteins that are required for exocytosis. The introduction of a synthetic peptide that corresponds to the carboxyl-terminal end sequence of Galpha(i3) into the cells specifically blocked this secretion. Similar results were obtained when antibodies to this peptide were introduced. The Galpha(i3) was located in both the Golgi and the plasma membrane, but only the latter source of Galpha(i3) appeared to be essential for secretion. These results indicate that Galpha(i3) functions to control regulated exocytosis in mast cells. C1 NHLBI,CHEM PHARMACOL LAB,BLDG 10,ROOM 8H108,BETHESDA,MD 20892. WEIZMANN INST SCI,DEPT CHEM IMMUNOL,IL-76100 REHOVOT,ISRAEL. NR 27 TC 218 Z9 221 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 3 PY 1993 VL 262 IS 5139 BP 1569 EP 1572 DI 10.1126/science.7504324 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MK329 UT WOS:A1993MK32900040 PM 7504324 ER PT J AU BENDELAC, A AF BENDELAC, A TI T-CELL RECEPTOR SPECIFICITY AND DIABETES IN NONOBESE DIABETIC MICE SO SCIENCE LA English DT Article RP BENDELAC, A (reprint author), NIAID,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 3 PY 1993 VL 262 IS 5139 BP 1582 EP 1583 DI 10.1126/science.8248809 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MK329 UT WOS:A1993MK32900045 PM 8248809 ER PT J AU YI, S HEGAMYER, G NAKAMURA, K KIM, HT OBERLEY, LW COLBURN, NH AF YI, S HEGAMYER, G NAKAMURA, K KIM, HT OBERLEY, LW COLBURN, NH TI ALTERATIONS OF THE P53 TUMOR-SUPPRESSOR GENE IN TRANSFORMED MOUSE-LIVER CELLS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID HUMAN CANCERS; EXPRESSION; MUTATION; DNA; CARCINOGEN; ONCOGENE; PROTEIN AB Mutational inactivation of p53, a potential tumor-suppressor gene, has been found in many tumors of humans as well as rodents. The p53 status in normal and transformed mouse liver cell lines has, however, not been investigated. We examined possible point mutations and compared mRNA and protein expression of the p53 gene in normal vs. transformed mouse liver cells. The transformed cells studied included lines spontaneously transformed by sub-culture, virally transformed by simian virus 40 (SV40), and chemically transformed by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) or methylcholanthrene epoxide (MC). A heterozygous G --> A point mutation at codon 241, position 1, of p53 was detected in MNNG-transformed cells after screening of 5 evolutionarily conserved regions where mutation hot-spots are clustered. The mutation causes a gly --> arg substitution. No mutations were found in normal or other transformed cells. The steady-state levels of p53 mRNA were decreased in chemically transformed (both MNNG- and MC-transformed) cells. Elevated levels of p53 protein were found in spontaneously transformed and SV40-transformed cells, an observation that may reflect a longer half-life of the protein, as has been shown in other transformed lines. The low level of the p53 protein in MC-transformed cells may result from transcriptional depression of the p53 gene. We conclude from these data that abnormal p53 status, such as point mutation or altered expression, may play a role during the malignant transformation of mouse liver cells. (C) 1993 Wiley-Liss, Inc. C1 UNIV IOWA,RADIAT RES LAB,IOWA CITY,IA 52242. RP YI, S (reprint author), NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701, USA. NR 30 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 2 PY 1993 VL 55 IS 6 BP 952 EP 956 PG 5 WC Oncology SC Oncology GA MM089 UT WOS:A1993MM08900012 ER PT J AU THEA, DM STLOUIS, ME ATIDO, U KANJINGA, K KEMBO, B MATONDO, M TSHIAMALA, T KAMENGA, C DAVACHI, F BROWN, C RAND, WM KEUSCH, GT AF THEA, DM STLOUIS, ME ATIDO, U KANJINGA, K KEMBO, B MATONDO, M TSHIAMALA, T KAMENGA, C DAVACHI, F BROWN, C RAND, WM KEUSCH, GT TI A PROSPECTIVE-STUDY OF DIARRHEA AND HIV-1 INFECTION AMONG 429 ZAIRIAN INFANTS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PERSISTENT DIARRHEA; AFRICAN CHILDREN; RURAL BANGLADESH; MALNUTRITION; ASSOCIATION; DURATION; MOTHERS; AIDS; BORN AB Background. Persistent diarrhea is a prominent feature of the acquired immunodeficiency syndrome in adults, but its cause and its effect on children with human immunodeficiency virus (HIV) infection are largely unknown, particularly in Africa. Methods. We studied a birth cohort of 429 infants born to HIV-positive or HIV-negative mothers in Zaire to determine the incidence of acute, recurrent (greater-than-or-equal-to 2 episodes), and persistent (greater-than-or-equal-to 14 days) diarrhea; outcome; and risk factors. Results. Of the 238 infants whose mothers were HIV-positive, 53 were infected, 139 were uninfected, and the HIV status of 46 could not be determined. As compared with uninfected infants, infected infants had higher incidence rates for acute diarrhea (170 vs. 100 episodes per 100 child-years, P = 0.003), recurrent diarrhea (21 vs. 11, P = 0.12), and persistent diarrhea (19 vs. 4, P<0.003). Persistent diarrhea developed in 11 HIV-infected infants; all but 1 died. It also developed in 19 uninfected infants; all but 1 survived. The prevalence of stool pathogens was similar in the two groups. In a multivariate model, persistent diarrhea in an infant was independently associated with symptomatic HIV type 1 infection in the mother (relative hazard, 1.5; P = 0.08). The incidence of persistent diarrhea in the uninfected infants of seropositive mothers was nearly double that in the uninfected infants of seronegative mothers (4.9 vs. 2.7 episodes per 100 child-years), and the risk increased if the mother died (relative hazard, 10.4). Significant growth impairment and severe immunosuppression occurred in the six to eight weeks before the onset of persistent diarrhea. Conclusions. In Zaire, infants with HIV infection have an 11-fold increased risk of death from diarrhea, largely persistent diarrhea, which is often preceded by recurrent episodes of acute diarrhea, malnutrition, or immunosuppression. illness and death of the mother increase that risk, even among her uninfected infants. C1 TUFTS UNIV NEW ENGLAND MED CTR,DIV GEOG MED & INFECT DIS,BOX 041,750 WASHINGTON ST,BOSTON,MA 02111. CTR DIS CONTROL & PREVENT,ATLANTA,GA. INT COOPERAT AIDS RES UNIT,PROJET SIDA,KINSHASA,ZAIRE. MAMA YEMO HOSP,DEPT PEDIAT,KINSHASA,ZAIRE. NIAID,BETHESDA,MD 20892. FU NIAID NIH HHS [P01-AI-26698] NR 27 TC 109 Z9 109 U1 0 U2 3 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 2 PY 1993 VL 329 IS 23 BP 1696 EP 1702 DI 10.1056/NEJM199312023292304 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA MJ707 UT WOS:A1993MJ70700004 PM 8232458 ER PT J AU MALOZOWSKI, S MAMALAKI, E PLETI, M ARMANDO, I GOLDSTEIN, D MERRIAM, GR AF MALOZOWSKI, S MAMALAKI, E PLETI, M ARMANDO, I GOLDSTEIN, D MERRIAM, GR TI INDUCTION OF REVERSIBLE GROWTH-RETARDATION AND GROWTH-HORMONE DEFICIENCY BY BLOCKADE OF NOREPINEPHRINE SYNTHESIS IN THE RAT SO ACTA ENDOCRINOLOGICA LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; ADULT MALE-RAT; MONOSODIUM GLUTAMATE; PLASMA-LEVELS; FEMALE RATS; SECRETION; MALNUTRITION; HYPOTHALAMUS; INHIBITION; EXPRESSION AB Norepinephrine is a major regulator of the release of growth hormone. Diethyldithiocarbamate, a dopamine-P-hydroxylase inhibitor, reduces norepinephrine synthesis and acutely inhibits growth hormone (GH) secretion. To investigate the long-term effects of dopamine-beta-hydroxylase blockade on growth, we administered diethyldithiocarbamate (0, 40, 100 or 400 mg/kg sc b.i.d.) to 21-day-old female rats for 10 days. Food intake, body weight, and tail length were measured twice a week. Plasma GH levels and hypothalamic dopamine and norepinephrine content were measured; messenger ribonucleic acids (mRNAs) for GH-releasing hormone and somatostatin were determined by quantitative in situ hybridization. Diethyldithiocarbamate administration decreased GH levels (p < 0.05) and retarded growth in a dose-dependent manner (p < 0.05), without altering food intake. Co-administration of GH partially reversed the growth retardation in diethyldithiocarbamate-treated animals (p < 0.05). Diethyldithiocarbamate treatment also increased the hypothalamic dopamine/norepinephrine ratio (1.13 vs 0.41 control, p < 0.05). Local levels of GH-releasing hormone and somatostatin mRNA were not altered by treatment. After discontinuation of diethyldithiocarbamate, growth rates returned to normal or transiently even to supranormal values. Norepinephrine synthesis blockade with diethyldithiocarbamate provides a model for reversible growth retardation, in which GH levels are decreased in the absence of decreased GH-releasing hormone mRNA. These results support a role for norepinephrine in the regulation of normal growth. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NINCDS,CLIN NEUROSCI BRANCH,BETHESDA,MD. AMER LAKE VAMC,SEATTLE,WA. UNIV WASHINGTON,DIV METAB ENDOCRINOL & NUTR,SEATTLE,WA. RP MALOZOWSKI, S (reprint author), US FDA,DIV METAB & ENDOCRINE DRUG PROD,5600 FISHERS LANE,HFD 510,ROCKVILLE,MD 20857, USA. NR 32 TC 1 Z9 1 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0001-5598 J9 ACTA ENDOCRINOL-COP JI Acta Endocrinol. PD DEC PY 1993 VL 129 IS 6 BP 554 EP 558 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MV578 UT WOS:A1993MV57800014 PM 7906468 ER PT J AU NOUSO, K BATTULA, N THORGEIRSSON, SS HIGASHI, T TSUJI, T AF NOUSO, K BATTULA, N THORGEIRSSON, SS HIGASHI, T TSUJI, T TI RECOMBINANT MOUSE CYTOCHROMES P-1-450 AND P-3-450 - ENZYMATIC CHARACTERIZATION OF THE HEMOPROTEIN EXPRESSED IN HUMAN-CELLS INFECTED WITH RECOMBINANT VACCINIA VIRUS SO ACTA MEDICA OKAYAMA LA English DT Article DE CYTOCHROME P-450; VACCINIA VIRUS; KINETICS ID METABOLIC-ACTIVATION; STABLE EXPRESSION; MAMMALIAN-CELLS; CDNA; AFLATOXIN-B1; PURIFICATION; INDUCTION; SEQUENCES; SYSTEM; DNA AB We expressed mouse cytochrome P-1-450 and P-3-450 using recombinant vaccinia virus gene expression system in HeLa cells that were devoid of significant basal levels of P-450. HeLa cells were infected with the recombinant vaccinia virus containing either mouse cytochrome P-1-450 or P-3-450 cDNA, and the cell lysates were analyzed for the kinetics of P-450 enzyme activity and protein expression at the same time. 7-Ethoxycoumarin O-deethylase and ethoxyresorufin O-deethylase activities were measured as an expression of the cytochrome P-450 enzyme activities. Both cell lines began to express these enzyme activities as early as 12h after infection. The activities increased linearly up to the 24h time point, and were kept for 36h. Western immunoblot analysis showed that these cytochrome P-450 protiens were detected at 16h and reached maximum quantity at 24h after infection. These data showed a good correlation between cytochrome P-450 enzyme activity and protein concentration throughout the process of P-450 gene expression by vaccinia virus vector, suggesting a complete formation of cytochrome P-450 holoenzyme from the early stage of the protein expression. C1 US FDA, DIV ANTIVIRAL DRUG PROD, KENSINGTON, MD 20857 USA. NCI, EXPTL CARCINOGENESIS LAB, BETHESDA, MD 20892 USA. RP NOUSO, K (reprint author), OKAYAMA UNIV, SCH MED, DEPT INTERNAL MED 1, OKAYAMA 700, JAPAN. NR 27 TC 1 Z9 1 U1 0 U2 0 PU OKAYAMA UNIV MED SCHOOL PI OKAYAMA PA EDITORIAL OFFICE, ACTA MEDICA OKAYAMA OKAYAMA UNIVERSITY MEDICAL SCHOOL 2-5-1 SHIKATA-CHO, KITA-KU, OKAYAMA, 700-8558, JAPAN SN 0386-300X J9 ACTA MED OKAYAMA JI Acta Med. Okayama PD DEC PY 1993 VL 47 IS 6 BP 377 EP 382 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA MP007 UT WOS:A1993MP00700004 PM 8128911 ER PT J AU HAUPT, R DOLCI, A NANTRON, M PRIOLO, E VITTONE, P GARAVENTA, A AF HAUPT, R DOLCI, A NANTRON, M PRIOLO, E VITTONE, P GARAVENTA, A TI NEUROBLASTOMA IV-S IN A PATIENT WITH BILATERAL MICROPHTHALMIA SO ACTA PAEDIATRICA LA English DT Note ID CANCER AB Neuroblastoma, a tumor of post-ganglionic sympathetic neurons, may be associated with a variety of genetic defects and congenital malformations (1). We report a case of neuroblastoma (NB) stage IV-S (2) in an infant with bilateral microphthalmia and other ocular malformations. C1 NCI,CLIN EPIDEMIOL BRANCH,BETHESDA,MD. G GASLINI CHILDRENS HOSP,DEPT OPHTHALMOL,GENOA,ITALY. G GASLINI CHILDRENS HOSP,DEPT PEDIAT HEMATOL ONCOL,GENOA,ITALY. RI Haupt, Riccardo/C-2237-2012 NR 8 TC 0 Z9 0 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD DEC PY 1993 VL 82 IS 12 BP 1085 EP 1086 DI 10.1111/j.1651-2227.1993.tb12820.x PG 2 WC Pediatrics SC Pediatrics GA MT443 UT WOS:A1993MT44300023 PM 8155934 ER PT J AU GRANT, BF AF GRANT, BF TI COMPARISON OF DSM-III-R AND DRAFT DSM-IV ALCOHOL-ABUSE AND DEPENDENCE IN A GENERAL-POPULATION SAMPLE SO ADDICTION LA English DT Note AB The purpose of this Data Note was to compare DSM-III-R and Draft DSM-IV formulations of alcohol use disorders in terms of prevalence and overlap in a representative sample of the United States general population. The prevalence of DSM-III-R and DSM-IV alcohol abuse and dependence combined were strikingly similar, despite discrepancies in the separate component diagnoses of abuse and dependence. The major finding of this study showed a reversal of the abuse-to-dependence ratio associated with the DSM-IV classification. Unlike previous surveys using DSM-III-R definitions, the prevalence of DSM-IV abuse exceeded that of dependence in this general population sample. Reasons for this discrepancy were discussed in terms of the differences in the number and content of abuse and dependence criteria and the relationship between abuse and dependence categories. The need for an explicit statement justifying the changes in the DSM-IV classification is highlighted. RP GRANT, BF (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,5600 FISHERS LANE,ROOM 14C-26,ROCKVILLE,MD 20857, USA. NR 10 TC 19 Z9 19 U1 0 U2 0 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD DEC PY 1993 VL 88 IS 12 BP 1709 EP 1716 DI 10.1111/j.1360-0443.1993.tb02047.x PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA ML460 UT WOS:A1993ML46000013 PM 8130711 ER PT J AU MASCOLA, JR MATHIESON, BJ ZACK, PM WALKER, MC HALSTEAD, SB BURKE, DS AF MASCOLA, JR MATHIESON, BJ ZACK, PM WALKER, MC HALSTEAD, SB BURKE, DS TI SUMMARY REPORT - WORKSHOP ON THE POTENTIAL RISKS OF ANTIBODY-DEPENDENT ENHANCEMENT IN HUMAN HIV VACCINE TRIALS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; FELINE INFECTIOUS PERITONITIS; HUMAN MONOCLONAL-ANTIBODIES; DENGUE HEMORRHAGIC-FEVER; U937 MONOCYTOID CELLS; DENDRITIC CELLS; MEDIATED ENHANCEMENT; ENHANCING ANTIBODIES; MOLECULAR-BIOLOGY; BLOOD MONOCYTES C1 NIAID,DIV AIDS,VACCINE RES & DEV BRANCH,BETHESDA,MD 20892. ROCKEFELLER FDN,DIV EYE DIS,NEW YORK,NY 10036. RP MASCOLA, JR (reprint author), WALTER REED ARMY INST RES,DIV RETROVIROL,13 TAFT COURT,ROCKVILLE,MD 20850, USA. OI /0000-0002-5704-8094 NR 66 TC 67 Z9 70 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD DEC PY 1993 VL 9 IS 12 BP 1175 EP 1184 DI 10.1089/aid.1993.9.1175 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA MQ904 UT WOS:A1993MQ90400002 PM 7908211 ER PT J AU DUBOIS, GC HODGE, DR HANSON, CA SAMUEL, KP ZWEIG, M SHOWALTER, SD PAPAS, TS AF DUBOIS, GC HODGE, DR HANSON, CA SAMUEL, KP ZWEIG, M SHOWALTER, SD PAPAS, TS TI PURIFICATION OF AN ESCHERICHIA-COLI-EXPRESSED NEF PROTEIN FROM THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-2 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HTLV-III; GENE-PRODUCT; HIV-1; AIDS; SEROCONVERSION; REPLICATION; ANTIBODIES; SEQUENCE; DOMAIN; CELLS AB The entire nef gene sequence of HIV-2, NIH-Z strain, has been cloned into the pJL6 expression vector and used for the synthesis of a 23-kDa protein in E. coli. The expressed protein is a fusion between the N-terminal 13 amino acids of the cII gene, 8 amino acids resulting from the ligation procedure, and the 180 amino acids that comprise the HIV-2 Nef sequence from the NIH-Z strain. The bacterially expressed Nef protein has been purified to apparent homogeneity on analytical scale (10-20 mug) by a combination of sequential detergent extraction, gel filtration, and reversed-phase high-performance chromatography. The expressed Nef protein is highly susceptible to proteolysis (chymotryptic-like activity) and this property accounts for the low yield obtained by gel filtration and RP-HPLC. Larger amounts (>100 mug) of the purified Nef protein have been produced by a purification procedure that employs sequential detergent extraction, chromatography on Q-Sepharose in the presence of 7 M urea, and chromatography on hydroxylapatite, also in 7 M urea. The purified HIV-2 Nef protein has been used for the production of polyclonal and monoclonal antibodies. The milder method of purification should facilitate structure-function studies of the Nef protein and its role in the life cycle of HIV. C1 NCI,FREDERICK CANC RES & DEV CTR,NUCLEIC ACID & PROTEIN SYNTHESIS LAB,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,MOLEC ONCOL LAB,FREDERICK,MD 21701. FU NCI NIH HHS [N0I-CO-74102] NR 33 TC 3 Z9 3 U1 0 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD DEC PY 1993 VL 9 IS 12 BP 1225 EP 1231 DI 10.1089/aid.1993.9.1225 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA MQ904 UT WOS:A1993MQ90400007 PM 8142139 ER PT J AU MATTSON, ME AF MATTSON, ME TI PROJECT MATCH - RATIONALE AND METHODS FOR A MULTISITE CLINICAL-TRIAL MATCHING PATIENTS TO ALCOHOLISM-TREATMENT SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ALCOHOLISM; PATIENT TREATMENT MATCHING; RANDOMIZED; CLINICAL TRIAL; COGNITIVE BEHAVIORAL THERAPY; 12-STEP FACILITATION THERAPY; MOTIVATIONAL ENHANCEMENT THERAPY ID PSYCHOTHERAPISTS; DEPRESSION; MODEL AB No single treatment approach is effective for all persons with alcohol problems. A more promising strategy involves assigning patients to alternative treatments based on specific needs and characteristics of patients. Project MATCH is a multisite clinical trial designed to test a series of a priori hypotheses on how patient-treatment interactions relate to outcome. Two independent but parallel matching studies are being conducted, one with clients recruited from outpatient settings, the other with patients receiving aftercare treatment following inpatient care. Patients are randomly assigned to Twelve-Step Facilitation, Cognitive Behavioral Coping Skills, or Motivational Enhancement Therapy. Subjects are followed at 3-month intervals for 1 year following completion of the 12-week treatment period and evaluated for changes in drinking patterns, functional status/quality of life, and treatment services utilization. Interaction effects with selected patient characteristics will be studied. Project MATCH will provide a rigorous test of the utility of patient-treatment matching in general and, depending on the specific a priori hypotheses validated, will have important implications for clinical practice. RP MATTSON, ME (reprint author), NIAAA,PARKLAWN BLDG,ROOM 14-C-20,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. RI Carroll, Kathleen/A-7526-2009; Cooney, Ned/C-5176-2014 OI Cooney, Ned/0000-0001-6698-8312 NR 57 TC 92 Z9 92 U1 0 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 1993 VL 17 IS 6 BP 1130 EP 1145 PG 16 WC Substance Abuse SC Substance Abuse GA MN395 UT WOS:A1993MN39500003 ER PT J AU FERTIG, JB ALLEN, JP CROSS, GM AF FERTIG, JB ALLEN, JP CROSS, GM TI CAGE AS A PREDICTOR OF HAZARDOUS ALCOHOL-CONSUMPTION IN US ARMY PERSONNEL SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE CAGE; ALCOHOLISM SCREENING; ALCOHOL INTAKE; ASSESSMENT; RECEIVER OPERATING CHARACTERISTICS ID QUESTIONNAIRE AB Sensitivities, specificities, and odds ratios for hazardous drinking for various cut scores on the CAGE are computed for a large sample active duty Army personnel. Contrasts on these properties are made between the standard CAGE and a ''modified CAGE'' consisting of standard CAGE items and two other items dealing with problematic drinking. The role of demographic variables-gender, ethnicity, marital status, rank category, and age in mediating relationships of both versions of the screening test to hazardous drinking-is also explored. At a cutoff score of one endorsed item, odds ratios were highest for female personnel and commissioned officers. C1 USA,OFF SURGEON GEN,WASHINGTON,DC 20310. RP FERTIG, JB (reprint author), NIAAA,DIV CLIN & PREVENT RES,TREATMENT RES BRANCH,ROOM 14-C20,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 15 TC 18 Z9 18 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 1993 VL 17 IS 6 BP 1184 EP 1187 DI 10.1111/j.1530-0277.1993.tb05225.x PG 4 WC Substance Abuse SC Substance Abuse GA MN395 UT WOS:A1993MN39500009 PM 8116828 ER PT J AU MARTINEZ, F THOMAS, NM DARBAN, H COX, TJ WOOD, S WATSON, RR AF MARTINEZ, F THOMAS, NM DARBAN, H COX, TJ WOOD, S WATSON, RR TI INTERLEUKIN-6 AND INTERLEUKIN-8 PRODUCTION BY MONONUCLEAR-CELLS OF CHRONIC-ALCOHOLICS DURING TREATMENT SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ALCOHOL; CYTOKINE; HUMAN; PERIPHERAL BLOOD MONONUCLEAR CELLS ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA; ETHANOL; HEPATITIS; CYTOKINE; IL-8; NEUTROPHILS; CIRRHOSIS; INJURY AB Chronic alcohol consumption has been associated with suppression of a number of immune parameters. This study was designed to investigate the relationship between chronic alcohol ingestion and cessation with respect to release of interleukin-6 (IL-6) and interleukin-8 (IL-8) using highly specific and sensitive ELISA assays, as well as a functional assay, natural killer cell cytotoxic activity. ELISAs were developed to determine the amount of IL-6 and IL-8 release by peripheral blood mononuclear cells (PBMCs). Two groups of subjects were recruited: young (18-22 years old), nonalcoholic users (controls) and long-term alcoholics (35-55 years old). Blood samples were collected at time 0 from all subjects and from alcoholics 28 days after treatment had begun and alcohol use had ceased. Then mitogen-stimulated release of cytokines by peripheral blood cells was determined. The abstaining controls, and the alcoholics, after 30 days of abstinence, tended to produce lower amounts of IL-6 and 11-8, although these differences were not statistically significant. Natural killer cell activity was not statistically different between the young groups, yet appeared to increase once alcohol use discontinued. Some of the cells from the controls (abstainers) were incubated with ethanol (EtOH). Its content in sealed wells was measured after the time of incubation of PBMCs. When EtOH was serially diluted in plates, some well-well diffusion was noted, but the maximum concentration of EtOH never fell below 0.3% from an initial concentration of 0.5%, and at no time was the EtOH concentration gradient completely lost, even after 66 hr of incubation. EtOH in vitro did not induce significant modulation of IL-6 or IL-8 release from subjects over the concentration range of ethanol tested (0.02-0.5%). Similarly, there was no statistically significant dependence of baseline (nonstimulated) release of IL-6 or IL-8 on the presence of EtOH in culture medium. C1 UNIV ARIZONA,DEPT FAMILY & COMMUNITY MED,NIAAA,ALCOHOL RES CTR,TUCSON,AZ 85724. VET ADM MED CTR,TUCSON,AZ. FU NIAAA NIH HHS [AA08037] NR 27 TC 16 Z9 16 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 DEC PY 1993 VL 17 IS 6 BP 1193 EP 1197 DI 10.1111/j.1530-0277.1993.tb05227.x PG 5 WC Substance Abuse SC Substance Abuse GA MN395 UT WOS:A1993MN39500011 PM 8116830 ER PT J AU SANCHEZ, JA MILEI, J YU, ZX STORINO, R WENTHOLD, R FERRANS, VJ AF SANCHEZ, JA MILEI, J YU, ZX STORINO, R WENTHOLD, R FERRANS, VJ TI IMMUNOHISTOCHEMICAL LOCALIZATION OF LAMININ IN THE HEARTS OF PATIENTS WITH CHRONIC CHAGASIC CARDIOMYOPATHY - RELATIONSHIP TO THICKENING OF BASEMENT-MEMBRANES SO AMERICAN HEART JOURNAL LA English DT Article ID EXTRACELLULAR-MATRIX; RAT MYOCARDIUM; ANTIBODIES; COMPONENTS; AUTOANTIBODIES; FIBRONECTIN; SERA AB Histologic, ultrastructural, and immunohistochemical studies were made of endomyocardial biopsy specimens from 10 patients with chronic chagasic cardiomyopathy. Histologic and electron microscopic observation disclosed marked thickening of the basement membranes of the myocytes, endothelial cells, and vascular smooth muscle cells in all patients. Light (peroxidase-labeled antibodies) and electron (gold-conjugated antibody) microscopic immunohistochemical methods revealed a positive reaction for laminin in these thickened basement membranes. This thickening of basement membranes may develop as a consequence of: (1) an immunologic reaction that is triggered by the presence of a laminin-like molecule on the surfaces of Trypanosoma cruzi amastigotes and trypomastigotes; (2) an immunologic response to direct injury of basement membranes causing some of their components to become antigenic; (3) myocardial fibrosis, with synthesis of new connective tissue components; and (4) a combination of the preceding factors. The relationship of these changes to antilaminin antibodies requires clarification. C1 NHLBI,PATHOL BRANCH,BLDG 10 2N240 9000 ROCKVILLE PIKE,BETHESDA,MD 20892. HOSP JUAN A FERNANDEZ,BUENOS AIRES,ARGENTINA. OI MILEI, JOSE/0000-0003-4029-5993 NR 31 TC 13 Z9 13 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD DEC PY 1993 VL 126 IS 6 BP 1392 EP 1401 DI 10.1016/0002-8703(93)90539-L PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA MK060 UT WOS:A1993MK06000017 PM 8249797 ER PT J AU SHIRANI, J ROBERTS, WC AF SHIRANI, J ROBERTS, WC TI CLINICAL AND MORPHOLOGIC FEATURES OF MITRAL-VALVE PROLAPSE IN OCTOGENARIANS SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Note C1 NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. NR 4 TC 2 Z9 2 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 DEC 1 PY 1993 VL 72 IS 17 BP 1316 EP 1319 DI 10.1016/0002-9149(93)90305-V PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA MJ980 UT WOS:A1993MJ98000020 PM 8256712 ER PT J AU JACOBSON, LP KIRBY, AJ POLK, S PHAIR, JP BESLEY, DR SAAH, AJ KINGSLEY, LA SCHRAGER, LK AF JACOBSON, LP KIRBY, AJ POLK, S PHAIR, JP BESLEY, DR SAAH, AJ KINGSLEY, LA SCHRAGER, LK TI CHANGES IN SURVIVAL AFTER ACQUIRED-IMMUNODEFICIENCY-SYNDROME (AIDS) - 1984-1991 SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE ACQUIRED IMMUNODEFICIENCY SYNDROME; ANTIGENS; CD4; COHORT STUDIES; HIV-1; IMMUNOSUPPRESSION; MORTALITY; SURVIVAL ID PNEUMOCYSTIS-CARINII PNEUMONIA; CONTROLLED TRIAL; VIRUS INFECTION; UNITED-STATES; NATURAL-HISTORY; ZIDOVUDINE; MORTALITY; COHORT; EXPERIENCE; TRENDS AB In a prospective cohort of 2,647 human immunodeficiency virus type 1 (HIV-1) seropositive homosexual men enrolled in Baltimore, Chicago, Los Angeles, and Pittsburgh, 891 developed clinical acquired immunodeficiency syndrome (AIDS) between June 1984 and January 1992. Cox proportional hazards models were used to examine temporal trends in survival after AIDS for specific diagnoses, controlling for level of immunosuppression at diagnosis, age, race, and geographic location. Median survival time following AIDS onset increased from 11.6 months in 1984-1985 to 19.5 months in 1988-1989; for those diagnosed in 1990-1991, the median survival time dropped to 17.2 months. Trends in improved survival were diagnosis-specific. Survival after Pneumocystis carinii pneumonia consistently improved from 1984 to 1991 (p < 0.001). Compared with men diagnosed in 1984-1985, those diagnosed with P. carinii pneumonia in 1990-1991 had one-tenth the hazard of dying. For men with greater than or equal to 100 helper T-lymphocytes (CD4+ cells) when diagnosed with Kaposi's sarcoma, the relative hazards (95% confidence intervals) of dying after Kaposi's sarcoma were 0.8 (0.42-1.60) in 1986-1987, 0.7 (0.34-1.58) in 1988-1989, and 0.6 (0.19-1.61) in 1990-1991 compared with those diagnosed before 1986. Men with <100 CD4+ cells when diagnosed with Kaposi's sarcoma did not demonstrate a consistent change in their subsequent survival. After a nonsignificant (p > 0.05) initial improvement in prognosis, there has not been a significant improvement in survival for men who presented with other opportunistic infections. Observed increases in overall survival probably relate to improved treatment of patients who develop P. carinii pneumonia. Limited improvement in survival following other AIDS diagnoses indicates the need for developing effective treatment against these diseases. C1 NORTHWESTERN UNIV, HOWARD BROWN MEM CLIN, SCH MED, CHICAGO, IL USA. UNIV CALIF LOS ANGELES, SCH PUBL HLTH, LOS ANGELES, CA USA. UNIV PITTSBURGH, GRAD SCH PUBL HLTH, PITTSBURGH, PA USA. NIAID, ROCKVILLE, MD USA. RP JACOBSON, LP (reprint author), JOHNS HOPKINS UNIV, SCH PUBL HLTH,DEPT EPIDEMIOL,HAMPTON HOUSE, ROOM 780, 624 N BROADWAY, BALTIMORE, MD 21205 USA. FU NIAID NIH HHS [U01-AI-35040, U01-AI-35039, U01-AI-35041] NR 29 TC 76 Z9 76 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 1 PY 1993 VL 138 IS 11 BP 952 EP 964 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ML879 UT WOS:A1993ML87900004 PM 7903022 ER PT J AU ZHENG, W MCLAUGHLIN, JK CHOW, WH CHIEN, HTC BLOT, WJ AF ZHENG, W MCLAUGHLIN, JK CHOW, WH CHIEN, HTC BLOT, WJ TI RISK-FACTORS FOR CANCERS OF THE NASAL CAVITY AND PARANASAL SINUSES AMONG WHITE MEN IN THE UNITED-STATES SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE ALCOHOL DRINKING; CASE-CONTROL STUDIES; DIET; MORTALITY; NASOPHARYNGEAL NEOPLASMS; OCCUPATIONS; SMOKING; TOBACCO SMOKE POLLUTION ID PASSIVE SMOKING; MAXILLARY SINUS; EXPOSURE; SHANGHAI; DIET; WOODWORKING; ASSOCIATION AB A case-control analysis of cancer of the nasal cavity and sinuses was performed using data from the 1986 National Mortality Followback Survey. Data on cigarette smoking, alcohol consumption, usual diet, and other factors from 147 white men who died from nasal cancer and from 449 controls who died from other causes were compared. Cigarette smoking was related to an increased risk of nasal cancer, with a doubling of risk among heavy or long-term smokers and a reduction in risk among long-term quitters. Among nonsmokers, having a spouse who smoked was associated with a significantly elevated risk of nasal cancer. After adjustment for smoking, a significant dose-response relation was also noted between alcohol drinking and risk of nasal cancer. High consumption of salted/smoked foods was associated with elevated risk, and risk tended to decrease with increasing intake of vegetables. Associations were more pronounced for cigarette smoking and certain dietary items when the analysis was restricted to maxillary sinus cancer. The study confirms that cigarette smoking is a risk factor for nasal cancer, and provides further evidence that dietary factors may play a role in the etiology of this malignancy. C1 NCI,DIV CANC ETIOL,BIOSTAT BRANCH,BETHESDA,MD. WESTAT CORP,ROCKVILLE,MD. NR 30 TC 40 Z9 41 U1 2 U2 3 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 1 PY 1993 VL 138 IS 11 BP 965 EP 972 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ML879 UT WOS:A1993ML87900005 PM 8256781 ER PT J AU YONG, LC KULLER, LH RUTAN, G BUNKER, C AF YONG, LC KULLER, LH RUTAN, G BUNKER, C TI LONGITUDINAL-STUDY OF BLOOD-PRESSURE - CHANGES AND DETERMINANTS FROM ADOLESCENCE TO MIDDLE-AGE - THE DORMONT-HIGH-SCHOOL FOLLOW-UP-STUDY, 1957-1963 TO 1989-1990 SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE ADOLESCENCE; AGE FACTORS; BLOOD PRESSURE; BODY WEIGHT; HYPERTENSION; LIFE STYLE; LONGITUDINAL STUDIES; MIDDLE AGE ID CORONARY HEART-DISEASE; PHYSICAL-ACTIVITY; RISK-FACTORS; ALCOHOL-CONSUMPTION; YOUNG ADULTHOOD; HYPERTENSION; MEN; FRAMINGHAM; CHILDHOOD; FITNESS AB The changes and determinants of blood pressure were examined in the Dormont High School (Pittsburgh, Pennsylvania) cohort of 86 men and 116 women with mean ages of 17 years during high school (1957-1963), 34 years at follow-up I (1977-1978), and 47 years at current follow-up II (1989-1990). Over the 30-year period, the subjects' mean systolic blood pressure changed relatively little, whereas the increase in mean diastolic blood pressure was significantly higher in men than in women (p < 0.01). Based on the criteria of diastolic blood pressure greater than or equal to 90 mmHg, and/or current use of antihypertensive medication, 18% developed hypertension. Compared with nonhypertensives, hypertensives had significantly higher baseline systolic blood pressure (p < 0.001); higher weight at all ages (p < 0.05); and gained more weight over the period (p < 0.01). By means of multivariate analyses, it was found that baseline systolic blood pressure, current weight, and weight gain were significantly and independently associated with current systolic blood pressure level and hypertension. These data indicate that initial systolic blood pressure level at adolescence, current weight, and weight gain are important determinants of risk of high blood pressure, and there is a further suggestion of sex and age differences in the critical period of risk. C1 UNIV PITTSBURGH,DEPT EPIDEMIOL,PITTSBURGH,PA 15261. NCI,DCPC,CPSB,BETHESDA,MD. VET AFFAIRS MED CTR,MEMPHIS,TN. NR 43 TC 70 Z9 72 U1 0 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 1 PY 1993 VL 138 IS 11 BP 973 EP 983 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ML879 UT WOS:A1993ML87900006 PM 8256782 ER PT J AU ABASSI, ZA KLEIN, H GOLOMB, E KEISER, HR AF ABASSI, ZA KLEIN, H GOLOMB, E KEISER, HR TI URINARY ENDOTHELIN - A POSSIBLE BIOLOGICAL MARKER OF RENAL DAMAGE SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE ENDOTHELIN; RENAL FAILURE; DIABETES MELLITUS; URINARY ENDOTHELIN AB Endothelin (ET) is a powerful vasoconstrictor peptide synthesized and secreted by the vascular endothelium. Significant amounts of ET are also produced by nonendothelial cells, mainly tubular-epithelial and mesangial cells. Large amounts of ET are found in the urine compared with the small amounts present in blood. Because most of the ET filtered from plasma is subject to degradation by neutral endopeptidase (EC 3.4.24.11) in the proximal tubule, urinary ET is probably of renal origin. The range of urinary ET excretion in healthy persons is 20 to 90 ng/day. The excretion of endothelin is modulated by several mechanical and chemical stimuli such as angiotensin IT, phenylephrine, radiocontrast media, cyclosporine, and cis-platin. In addition, enhanced urinary ET excretion has been found in several forms of renal failure, both acute and chronic, and in diabetes mellitus. Thus, urinary ET has the potential of serving as a marker for renal disease. RP ABASSI, ZA (reprint author), NHLBI,HYPERTENS ENDOCRINE BRANCH,BLDG 10,ROOM 8C103,BETHESDA,MD 20892, USA. NR 0 TC 38 Z9 39 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD DEC PY 1993 VL 6 IS 12 BP 1046 EP 1054 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MN987 UT WOS:A1993MN98700010 PM 8136095 ER PT J AU HAYES, RB DOSEMECI, M RISCIGNO, M BLAIR, A AF HAYES, RB DOSEMECI, M RISCIGNO, M BLAIR, A TI CANCER MORTALITY AMONG JEWELRY WORKERS SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE MALIGNANT NEOPLASMS; JEWELER DEATHS; PROPORTIONAL MORTALITY ID OCCUPATIONAL EXPOSURE; INDUSTRY; COHORT; MORBIDITY; DEATH; SOLVENTS; RISKS; MEN AB Mortality was investigated for the years 1950-1980 for 1,009 male members of a New York jewelry workers union, and for the years 1984-1989 among 919 men and 605 women identified as jewelry workers on death certificates from 24 states. Malignant neoplasms were excessive for male union members (proportional mortality ratio [PMR] = 1.17; 95% confidence interval [CI]: 1.02-1.33) and female jeweler deaths from the 24 states (PMR = 1.24; 95% CI: 1.07-1.42). Deaths due to nonmalignant causes were not unusual, except for excesses, in union males, of the circulatory system (PMR = 1.10; 95% CI: 1.02-1.19), including arteriosclerotic heart disease (PMR = 1.25; 95% CI: 1.14-1.37) and rheumatic heart disease (PMR = 3.02; 95% CI: 1.94-4.50). Cancers of the digestive tract were proportionally elevated among union males (proportional cancer mortality rate [PMR] = 1.13; 95% CI: 0.89-1.41) and among deaths from the 24 states (PCMR = 1.22; 95% CI: 1.01-1.47). For the 24 states, excesses for digestive cancer were found for both males (PCMR = 1.19; 95% CI: 0.90-1.54) and females (PCMR = 1.26; 95% CI: 0.96-1.62). Regarding specific sites in the digestive tract, colon cancer excesses were found in union males (PCMR = 1.53: 95% CI: 1.05-2.15), and for men (PCMR = 1.27; 95% CI: 0.82-1.88) and women (PCMR = 1.36; 95% CI: 0.92-3.27) in 24 states. Also, in the 24 states, excesses were noted for esophageal cancer (PMR = 2.03; 95% CI: 1.08-3.47) and stomach cancer (PCMR = 1.66; 95% CI: 0.95-2.69), due to excess stomach cancer in women (PCMR = 2.50; 95% CI: 1.20-4.61). Marginal proportional excesses were found for malignancies of the hematolymphopoietic system in union males (PCMR = 1.12; 95% CI: 0.72-1.67) and among deaths from 24 states (PCMR = 1.23; 95% CI: 0.90-1.66), particularly due to non-Hodgkin's lymphoma deaths (PCMR = 1.39; 95% CI: 0.93-2.00). The wide variety of exposures in this industry, particularly to metals and solvents, could possibly involve excess risk for malignancy at these sites. (C) 1993 Wiley-Liss, Inc. C1 WESTAT CORP,ROCKVILLE,MD. RP HAYES, RB (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892, USA. NR 37 TC 11 Z9 11 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD DEC PY 1993 VL 24 IS 6 BP 743 EP 751 DI 10.1002/ajim.4700240611 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA MJ627 UT WOS:A1993MJ62700010 PM 8311104 ER PT J AU ZAHM, SH BLAIR, A AF ZAHM, SH BLAIR, A TI CANCER AMONG MIGRANT AND SEASONAL FARMWORKERS - AN EPIDEMIOLOGIC REVIEW AND RESEARCH AGENDA SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE AGRICULTURE; MIGRANTS; CANCER; MORTALITY; OCCUPATION; PESTICIDES; EPIDEMIOLOGIC RESEARCH; FARMWORK ID UNITED-STATES; AGRICULTURAL-WORKERS; BLADDER-CANCER; FARM-WORKERS; RISK-FACTORS; MORTALITY; HEALTH; PATTERNS AB There are an estimated three million hired migrant and seasonal farmworkers in the United States. Adults and children may be exposed to mutagenic and potentially carcinogenic pesticides during planting, weeding, thinning, and harvesting crops. Field conditions that provide little opportunity to wash skin or clothing to minimize pesticide absorption may intensify exposure. Little is known, however, about the occurrence of cancer in migrant or seasonal farmworkers. Most cancer epidemiologic research on agricultural populations has focussed on farm owner/operators. The few studies that have evaluated cancer in farmworkers suggest that, like farm owner/operators, they may be experiencing excesses of multiple myeloma and cancers of the stomach, prostate, and testis. A few studies suggest that the farmworkers may differ from farmers by experiencing excesses of cancers of the buccal cavity and pharynx, lung, and liver. Cervical cancer was elevated in female farmworkers in one study. Descriptive data and etiologic research on cancer among farmworkers and family members are urgently needed. Feasibility evaluations, however, should precede etiologic investigations because of possible difficulties in studying this population of workers. Issues that need to be evaluated include assessing where and when farmworkers and family members are diagnosed and/or treated for malignancies, the ability of farmworkers to provide histories of crops, locations, and years worked and living conditions, the ability of agricultural experts to determine likely pesticide exposures based on such farmworkers' histories, the ability to obtain information on potential confounding factors, the ability to recontact or determine vital status of specific farmworkers over time, the suitability of conducting studies in home-base vs. upstream counties, and the ability to study agriculturally related malignancies in persons who have left farm work before the disease occurs. (C) 1993 Wiley-Liss, Inc. RP ZAHM, SH (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,OCCUPAT STUDIES SECT,EXECUT PLAZA N,ROOM 418,ROCKVILLE,MD 20892, USA. RI Zahm, Shelia/B-5025-2015 NR 54 TC 63 Z9 64 U1 0 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD DEC PY 1993 VL 24 IS 6 BP 753 EP 766 DI 10.1002/ajim.4700240612 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA MJ627 UT WOS:A1993MJ62700011 PM 8311105 ER PT J AU STRIKER, GE AF STRIKER, GE TI USRDS DATA TO BE MORE ACCESSIBLE TO BIOMEDICAL COMMUNITY SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Note RP STRIKER, GE (reprint author), NIDDKD,DIV KIDNEY UROL & HEMATOL DIS,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD DEC PY 1993 VL 22 IS 6 BP 884 EP 884 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA MK124 UT WOS:A1993MK12400017 ER PT J AU YOON, BH ROMERO, R ROH, CR KIM, SH AGER, JW SYN, HC COTTON, D KIM, SW AF YOON, BH ROMERO, R ROH, CR KIM, SH AGER, JW SYN, HC COTTON, D KIM, SW TI RELATIONSHIP BETWEEN THE FETAL BIOPHYSICAL PROFILE SCORE, UMBILICAL ARTERY DOPPLER VELOCIMETRY, AND FETAL BLOOD ACID-BASE STATUS DETERMINED BY CORDOCENTESIS SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE FETAL BIOPHYSICAL PROFILE; UMBILICAL ARTERY DOPPLER VELOCIMETRY; FETAL ACID-BASE STATUS; CORDOCENTESIS ID GAS VALUES; CESAREAN-SECTION; PH; BIRTH; HYPOXIA; FETUSES; NEWBORN; AGE AB OBJECTIVE: Fetal hypoxia-acidosis is part of the terminal pathway leading to intrauterine fetal death. A central premise of antepartum surveillance is that identification and timely delivery of the hypoxic or acidotic fetus will prevent intrauterine death and decrease long-term neurologic damage. The optimal method to identify fetal hypoxia-acidosis has not been determined. We attempted to compare the performance of the biophysical profile score and umbilical artery Doppler velocimetry in the identification of fetal acidemia, hypoxemia, and hypercarbia as determined by pH and gas analysis of fetal blood obtained by cordocentesis. STUDY DESIGN: Fetal biophysical profile and umbilical artery Doppler velocimetry studies were performed before cordocentesis in 24 patients (26 to 40 weeks). Umbilical vein pH and blood gas values were determined in all cases. The pulsatility index of the umbilical artery was obtained with pulsed Doppler equipment. Receiver-operator characteristic curve analysis and stepwise multiple logistic regression were performed to examine the relationship between biophysical profile score, umbilical artery Doppler velocimetry, and acid-base status. RESULTS: The prevalence of fetal acidemia (pH 2 SD below the mean for gestational age) was 41.7% (10/24). There was a significant relationship between the change in umbilical artery pulsatility index and fetal acidemia (chi2 = 26.6, p < 0.001) and hypercarbia (chi2 = 22.9, p < 0.001), but not hypoxemia (chi2 = 1.0, p > 0.1), and between the biophysical profile score and fetal acidemia (chi2 = 11.1, p < 0.001) and hypercarbia (chi2 = 9.0, p < 0.005), but not hypoxemia (chi2 = 2.3, p > 0.1). Stepwise multiple logistic regression demonstrated that umbilical artery Doppler velocimetry was a better explanatory variable for acidemia and hypercarbia than the biophysical profile score. CONCLUSION: A strong relationship between the degree of fetal acidemia and hypercarbia and the results of umbilical artery Doppler velocimetry and biophysical profile was found. However, umbilical artery Doppler velocimetry was a better explanatory variable for these outcomes than the biophysical profile score. C1 SEOUL NATL UNIV,COLL MED,DEPT OBSTET & GYNECOL,SEOUL 151,SOUTH KOREA. WAYNE STATE UNIV,DEPT OBSTET & GYNECOL,DETROIT,MI 48202. NICHHD,PERINATOL BRANCH,BETHESDA,MD 20892. RI Yoon, Bo Hyun/H-6344-2011 NR 25 TC 31 Z9 32 U1 0 U2 4 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 1993 VL 169 IS 6 BP 1586 EP 1594 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA MN383 UT WOS:A1993MN38300038 PM 8267067 ER PT J AU BLESSED, WB SEPULVEDA, W ROMERO, R BERRY, SM KING, ME COTTON, DB AF BLESSED, WB SEPULVEDA, W ROMERO, R BERRY, SM KING, ME COTTON, DB TI PRENATAL-DIAGNOSIS OF SPONTANEOUS RUPTURE OF THE FETAL BLADDER WITH COLOR DOPPLER ULTRASONOGRAPHY SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE BLADDER RUPTURE; URINARY ASCITES; COLOR DOPPLER ULTRASONOGRAPHY; PRENATAL DIAGNOSIS AB Rupture of the fetal-neonatal bladder that results in urinary ascites has rarely been reported in the literature. In this report we present the first case of spontaneous rupture of the fetal bladder in which the diagnosis was made prenatally by means of color Doppler ultrasonography. C1 WAYNE STATE UNIV,HUTZEL HOSP,SCH MED,DEPT OBSTET & GYNECOL,4707 ST ANTOINE BLVD,DETROIT,MI 48201. NICHHD,PERINATOL BRANCH,BETHESDA,MD 20892. NR 3 TC 7 Z9 7 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 1993 VL 169 IS 6 BP 1629 EP 1631 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA MN383 UT WOS:A1993MN38300052 PM 8267080 ER PT J AU PRICE, RA CHARLES, MA PETTITT, DJ KNOWLER, WC AF PRICE, RA CHARLES, MA PETTITT, DJ KNOWLER, WC TI OBESITY IN PIMA-INDIANS - LARGE INCREASES AMONG POST-WORLD-WAR-II BIRTH COHORTS SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Article DE BODY MASS INDEX; OBESITY; PIMA INDIANS; PREVALENCE; SECULAR INCREASE; TEMPORAL INCREASE ID BODY-MASS INDEX; DANISH YOUNG MEN; SECULAR TRENDS; UNITED-STATES; SKINFOLD THICKNESS; SOCIOECONOMIC-FACTORS; SCHOOLCHILDREN; CONSUMPTION; NUTRITION; WEIGHT AB Several studies have shown secular increases in obesity during the past 35 years, and others have reported increases in dietary fat consumption during the same period. Here we report a dramatic increase in obesity among Pima Indians born after World War II that appears to be associated with increased exposure to Western customs and diet following 1945. We examined the body mass index (BMI = weight in kilograms/height(2) in meters) of 1,128 male and 1,372 female Pima Indians aged 15-65 years who were born between 1901 and 1964 and were examined between 1965 and 1990. We found large increases in BMI among Pima Indian men and women in post-World War II birth cohorts (1945 and later). The parallel changes in body mass index, dietary fat, and exposure to Western culture following World War II suggest that culturally mediated changes in diet and level of physical activity associated with modern industrialized society may have led to the large increases in obesity in the Pima Indians and to smaller parallel changes observed worldwide in westernized countries. (C) 1993 Wiley-Liss, Inc. C1 NIDDKD,PHOENIX,AZ. RP PRICE, RA (reprint author), UNIV PENN,SCH MED,DEPT PSYCHIAT,422 CURIE BLVD,CRB-145B,PHILADELPHIA,PA 19104, USA. FU NIDDK NIH HHS [DK44073]; NIMH NIH HHS [MH43409] NR 22 TC 46 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 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PD DEC PY 1993 VL 92 IS 4 BP 473 EP 479 DI 10.1002/ajpa.1330920406 PG 7 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA MM187 UT WOS:A1993MM18700005 PM 8296876 ER PT J AU WHITE, MJ RINTALA, DH HART, KA FUHRER, MJ AF WHITE, MJ RINTALA, DH HART, KA FUHRER, MJ TI SEXUAL ACTIVITIES, CONCERN AND INTERESTS OF WOMEN WITH SPINAL-CORD INJURY LIVING IN THE COMMUNITY SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE SPINAL CORD INJURY; SEXUALITY; LIFE SATISFACTION; SEXUAL CONCERNS; WOMEN ID ISSUES AB A representative sample of 40 women selected from a community-based sampling frame of 661 men and women with spinal cord injury was studied for sexual activities, concerns and interests. Participants responded to a questionnaire and rating scales and were physically examined to establish their neurologic status. With respect to 11 other areas of life, sex life ranked tenth in importance and tenth in satisfaction. In the sample, 65% reported having had a physical relationship (not necessarily including intercourse) in the past 12 months. Areas of greatest concern were problems associated with urinary and bowel accidents and not satisfying a partner. Regarding topics of interest related to sexual activity, highest priorities were assigned to coping emotionally with changes in sexual functioning and helping a partner cope emotionally with limitations on sexual activity. Compared with a previously studied group of men with spinal cord injury, the women in the sample exhibited distinctive needs that were not being addressed sufficiently by rehabilitation professionals. C1 INST REHABIL & RES,HOUSTON,TX. NICHHD,NATL CTR MED REHABIL RES,ROCKVILLE,MD. RP WHITE, MJ (reprint author), UNIV TEXAS,HLTH SCI CTR,BAYLOR COLL MED,SCH NURSING,1100 HOLOCOMBE 5514,HOUSTON,TX 77030, USA. NR 18 TC 40 Z9 40 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD DEC PY 1993 VL 72 IS 6 BP 372 EP 378 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA MP702 UT WOS:A1993MP70200007 PM 8260131 ER PT J AU CHOU, CL NIELSEN, S KNEPPER, MA AF CHOU, CL NIELSEN, S KNEPPER, MA TI STRUCTURAL-FUNCTIONAL CORRELATION IN CHINCHILLA LONG LOOP OF HENLE THIN LIMBS - A NOVEL PAPILLARY SUBSEGMENT SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE THIN DESCENDING LIMB; THIN ASCENDING LIMB; ULTRASTRUCTURE; CHIP28 WATER CHANNEL PROTEIN; RENAL MEDULLA; OSMOTIC WATER PERMEABILITY ID INTEGRAL MEMBRANE-PROTEIN; CELL CHIP28 PROTEIN; FREEZE-FRACTURE; WATER CHANNELS; RENAL TUBULES; ULTRASTRUCTURE; PERFUSION; HAMSTER AB The ultrastructural characteristics of thin limb subsegments from chinchilla long loops of Henle were studied in perfusion-fixed kidneys and in isolated perfused tubules. In sections from the perfusion-fixed kidneys, we noted types I, II, III, and IV thin limb epithelia similar to those previously identified in other rodent species. Sections from the deepest 20% of the papillary tip, however, revealed only a single thin limb epithelial type, which had a combination of structural characteristics distinct from previously identified thin limb subtypes. This ''papillary type'' epithelium had relatively tall cells and a complex cellular organization with extensive interdigitation, numerous shallow tight junctions, and microvilli. In single-tubule studies, thin limb segments dissected from different levels of the outer and inner medulla were perfused in vitro for osmotic water permeability (P(f)) measurements and were fixed for ultrastructural examination. Long-loop thin descending limbs (LDL) dissected from the outer medullar (P(f), 2,637 +/- 336 mum/s) had type II epithelium. LDL dissected from the middle of the inner medulla (P(f), 1,570 +/- 76 mum/s) had a type III epithelium. LDL segments dissected from the deepest 20% of the inner medulla had a low but nonzero P(f) (68 +/- 9 mum/s) and had the same novel papillary type epithelium seen in sections from fixed kidneys. Thin ascending limbs dissected from inner 50% of the inner medulla had essentially zero P(f) (8 +/- 4 mum/s) and had a type IV epithelium. Immunohistochemical localization of CHIP28 water channel protein confirmed the presence of CHIP28 in thin descending limbs throughout the outer 75% of the inner medulla, whereas labeling was essentially absent in the deep inner medulla where the low-P(f) LDL (novel papillary type epithelium) is located. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. AARHUS UNIV,INST ANAT,DEPT CELL BIOL,DK-8000 AARHUS,DENMARK. NR 25 TC 33 Z9 33 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 DEC PY 1993 VL 265 IS 6 BP F863 EP F874 PN 2 PG 12 WC Physiology SC Physiology GA MQ657 UT WOS:A1993MQ65700093 PM 7506872 ER PT J AU DAI, YS BAUM, BJ AF DAI, YS BAUM, BJ TI RELATIONSHIP BETWEEN MUSCARINIC RECEPTOR OCCUPANCY AND RESPONSE IN RAT PAROTID ACINAR-CELLS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE SPARE RECEPTOR; SPARE MEDIATOR; MUSCARINIC CHOLINERGIC RECEPTOR; INOSITOL TRISPHOSPHATE FORMATION; L-[N-METHYL-H-3]SCOPOLAMINE METHYL CHLORIDE BINDING ID CHOLINERGIC RECEPTORS; ADRENERGIC-RECEPTORS; SECRETION; STIMULATION; HYDROLYSIS; INHIBITION; ACTIVATION; RESERVE; CYCLASE; BINDING AB To determine whether spare muscarinic cholinergic receptors (mAChRs) exist in rat parotid acinar cells, we examined the effect of propylbenzilylcholine mustard (PBCM) on agonist (carbachol)-stimulated inositol trisphosphate (IP3) formation and on mAChR number, using l-[N-methyl-H-3]scopolamine methyl chloride (NMS)-binding assays. Treatment with PBCM (1, 3, 10, 30, 50 nM) for 15 min caused a 5, 22, 60, 66, and 72% decrease, respectively, in maximal IP3 formation stimulated by carbachol as well as a large reduction in the potency of carbachol in eliciting this response. Using these data, equilibrium constants (K(a)) for activation of the mAChRs by carbachol were calculated. These K(a) values agreed well with K(d) values of high-affinity mAChR binding sites determined from carbachol displacement of [H-3]NMS binding in parotid acinar cells. Reduction in mAChR number after PBCM treatment was determined by Scatchard analysis of specific [H-3]-NMS binding sites and compared with the expected reduction (q values) calculated from dose-response curves for carbachol-stimulated IP3 formation before and after PBCM treatment. PBCM (1, 3,10,30 nM) decreased mAChR maximal binding in cells 47.5, 68.9, 82.4, and 85.3%, respectively, which did agree with the approximately 38, 70, 90, and 92% decrease in receptor number expected from the calculated q values. Data demonstrate that PBCM irreversibly inactivates mAChRs in rat parotid cells, and the decrease in receptor number, measured directly from [H-3]NMS binding or calculated from receptor theory, is greater than that observed for stimulated IP3 production. These results suggest that a modest (30-40%) population of spare receptors exists for mAChR-mediated IP3 production in rat parotid glands. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BLDG 10,RM 1N113,BETHESDA,MD 20892. NR 21 TC 8 Z9 8 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 DEC PY 1993 VL 265 IS 6 BP G1122 EP G1127 PN 1 PG 6 WC Physiology SC Physiology GA MQ656 UT WOS:A1993MQ65600068 ER PT J AU SALIVE, ME COLLINS, KS FOLEY, DJ GEORGE, LK AF SALIVE, ME COLLINS, KS FOLEY, DJ GEORGE, LK TI PREDICTORS OF NURSING-HOME ADMISSION IN A BIRACIAL POPULATION SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article AB Racial differences in predictors of institutionalization were studied in a biracial North Carolina cohort (n = 4074). During 3 years of follow-up, 8.5% of Whites and 6.4% of African Americans were admitted to nursing homes. African Americans were one half as likely as Whites to be institutionalized after adjustment for other risk factors. Among Whites, impaired activities of daily living and cognition were the strongest predictors; among African Americans, impaired instrumental activities of daily living and prior history of nursing home use were strongest. Racial differences in nursing home use were not explained by financial and social support or physical and cognitive impairment. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,GEN PREVENT MED RESIDENCY PROGRAM,BALTIMORE,MD 21205. DUKE UNIV,CTR STUDY AGING & HUMAN DEV,DURHAM,NC 27706. RP SALIVE, ME (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,7201 WISCONSIN AVE,GATEWAY BLDG,BETHESDA,MD 20892, USA. FU NIA NIH HHS [N01-AG-1-2102] NR 19 TC 51 Z9 51 U1 3 U2 3 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 1993 VL 83 IS 12 BP 1765 EP 1767 DI 10.2105/AJPH.83.12.1765 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA MM041 UT WOS:A1993MM04100029 PM 8259815 ER PT J AU ROBINS, LN MILLS, JL AF ROBINS, LN MILLS, JL TI EFFECTS OF IN-UTERO EXPOSURE TO STREET DRUGS SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Review ID PRENATAL COCAINE EXPOSURE; NARCOTIC-DEPENDENT WOMEN; INFANT-DEATH-SYNDROME; MATERNAL COCAINE; SUBSTANCE ABUSE; BIRTH-WEIGHT; FOLLOW-UP; ESOPHAGEAL CANCER; MARIJUANA USE; FETAL GROWTH C1 NICHHD,BETHESDA,MD 20892. RP ROBINS, LN (reprint author), WASHINGTON UNIV,SCH MED,ST LOUIS,MO 63110, USA. NR 114 TC 1 Z9 1 U1 1 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 1993 VL 83 SU S BP S1 EP & PG 0 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA MN025 UT WOS:A1993MN02500001 ER PT J AU ESTRADAFRANCO, JG LANZARO, GC MA, MC WALKERABBEY, A ROMANS, P GALVANSANCHEZ, C CESPEDES, JL VARGASSAGARNAGA, R LAUGHINGHOUSE, A COLUMBUS, I GWADZ, RW AF ESTRADAFRANCO, JG LANZARO, GC MA, MC WALKERABBEY, A ROMANS, P GALVANSANCHEZ, C CESPEDES, JL VARGASSAGARNAGA, R LAUGHINGHOUSE, A COLUMBUS, I GWADZ, RW TI CHARACTERIZATION OF ANOPHELES-PSEUDOPUNCTIPENNIS SENSU-LATO FROM 3 COUNTRIES OF NEOTROPICAL AMERICA FROM VARIATION IN ALLOZYMES AND RIBOSOMAL DNA SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID CULICIDAE; GAMBIAE; DIPTERA; POPULATION; SPECIATION; MOSQUITO; PROBE; GENE AB Enzyme electrophoresis and restriction fragment length polymorphism (RFLP) analysis of Anopheles pseudopunctipennis sensu lato from nine isolated populations in neotropical America confirmed previous observations that it constitutes a species complex. Electrophoretic studies showed fixed differences at two enzyme loci, glycerol dehydrogenase (Gcd) and phosphoglucomutase (Pgm), suggesting limited or no gene flow between populations from Mexico and South America. In addition, analysis of genetic distance showed two distinctive clusters, one from Mexico and the other from South America, separated at a Nei's distance level of 0. 1 3, a value consistent in magnitude with that of other anopheline sibling species. The RFLP analysis revealed the presence of a ribosomal DNA fragment in Mexican strains that was absent in strains from South America. Two species have been identified through these studies, one provisionally named An. pseudopunctipennis A, a species from central Mexico, and the other An. pseudopunctipennis B, for the species found in the interAndean valleys and Andean slopes in regions of Peru and Bolivia. This research provides information required to elucidate the status of the different species of the An. pseudopunctipennis complex as vectors of malaria in the Americas. C1 MARYLAND BIOTECHNOL INST,CTR AGR BIOTECHNOL,COLL PK,MD. NIAID,MALARIA RES LAB,BETHESDA,MD 20892. BIOMED RES INST,ROCKVILLE,MD. UNIV TORONTO,DEPT ZOOL,TORONTO M5S 1A1,ONTARIO,CANADA. SECRETARIA SALUD & BIENESTAR SOCIAL ESTADO MORELUS,CUERNAVACA,MEXICO. MINIST PREVIS SOCIAL & SALUD PUBL,DIRECC NACL EPIDEMIL,LA PAZ,BOLIVIA. UNIV PERUANA CAUETANO HEREDIA,LIMA,PERU. RP ESTRADAFRANCO, JG (reprint author), UNIV MARYLAND,DEPT ENTOMOL,COLL PK,MD 20742, USA. NR 34 TC 22 Z9 22 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 DEC PY 1993 VL 49 IS 6 BP 735 EP 745 PG 11 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA MR261 UT WOS:A1993MR26100011 PM 7904129 ER PT J AU ESTRADAFRANCO, JG MA, MC GWADZ, RW SAKAI, R LANZARO, GC LAUGHINGHOUSE, A GALVANSANCHEZ, C CESPEDES, JL VARGASSAGARNAGA, R AF ESTRADAFRANCO, JG MA, MC GWADZ, RW SAKAI, R LANZARO, GC LAUGHINGHOUSE, A GALVANSANCHEZ, C CESPEDES, JL VARGASSAGARNAGA, R TI EVIDENCE THROUGH CROSSMATING EXPERIMENTS OF A SPECIES COMPLEX IN ANOPHELES-PSEUDOPUNCTIPENNIS SENSU-LATO - A PRIMARY MALARIA VECTOR OF THE AMERICAN CONTINENT SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID HYBRID MALE-STERILITY; CULICIDAE; DIPTERA; CROSSES AB Crossmating experiments were conducted to determine if postmating reproductive barriers are involved in the maintenance of genetic divergence among populations of Anopheles pseudopunctipennis sensu lato, a primary malaria vector of the American continent. Reciprocal crosses were conducted between colony and wild strains from Mexico, Bolivia, and Peru. Hybridization experiments revealed unidirectional male/female hybrid sterility in crosses between Mexican females and South American males. The data presented provide the first evidence that genetic differences exist among geographic strains of An. pseudopunctipennis in neotropical America. There is a consistent pattern suggesting the presence of at least two allopatric sibling species. One species occurs in central Mexico, the other in the South American Andean Cordillera. C1 MARYLAND BIOTECHNOL INST,CTR AGR BIOTECHNOL,COLL PK,MD. NIAID,MALARIA RES LAB,BETHESDA,MD 20892. BIOMED RES INST,ROCKVILLE,MD. UNIV TORONTO,DEPT ZOOL,TORONTO M5S 1A1,ONTARIO,CANADA. SECRETARIA SALUD & BIENESTAR SOCIAL ESTADO MORELOS,CUERNAVACA,MEXICO. MINIST PREVIS SOCIAL & SALUD PUBL,DIRECC NALL EPIDEMIOL,LA PAZ,BOLIVIA. UNIV PERUANA CAUETANO HEREDIA,LIMA,PERU. RP ESTRADAFRANCO, JG (reprint author), UNIV MARYLAND,DEPT ENTOMOL,COLL PK,MD 20742, USA. NR 25 TC 21 Z9 22 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 DEC PY 1993 VL 49 IS 6 BP 746 EP 755 PG 10 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA MR261 UT WOS:A1993MR26100012 PM 8279641 ER PT J AU DARAWSHE, S RIVAS, G MINTON, AP AF DARAWSHE, S RIVAS, G MINTON, AP TI SEDIMENTATION EQUILIBRIUM-QUANTITATIVE POLYACRYLAMIDE-GEL ELECTROPHORESIS (SE-QPAGE) - A NEW TECHNIQUE FOR THE DETECTION OF ASSOCIATIONS IN MULTICOMPONENT SOLUTIONS SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID ESCHERICHIA-COLI RP DARAWSHE, S (reprint author), NIDDKD,BIOCHEM PHARMACOL LAB,BETHESDA,MD 20892, USA. OI Rivas, German/0000-0003-3450-7478 NR 25 TC 6 Z9 6 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD DEC PY 1993 VL 215 IS 2 BP 236 EP 242 DI 10.1006/abio.1993.1581 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA MK886 UT WOS:A1993MK88600011 PM 8122784 ER PT J AU CHROUSOS, GP DETERAWADLEIGH, SD KARL, M AF CHROUSOS, GP DETERAWADLEIGH, SD KARL, M TI SYNDROMES OF GLUCOCORTICOID RESISTANCE SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID PRIMARY CORTISOL RESISTANCE; HORMONE-BINDING DOMAIN; RHEUMATOID-ARTHRITIS; DNA-BINDING; MINERALOCORTICOID RECEPTOR; FUNCTIONAL DOMAINS; GENE-TRANSCRIPTION; CUSHINGS-SYNDROME; TRANS-ACTIVATION; THYROID-HORMONE AB Glucocorticoid resistance results from the partial, albeit apparently generalized, inability of glucocorticoids to exert their effects on target tissues. The condition is associated with compensatory increases in circulating pituitary corticotropin and cortisol, with the former causing excess secretion of both adrenal androgens and adrenal steroid biosynthesis intermediates with salt-retaining activity. The manifestations of glucocorticoid resistance vary from chronic fatigue (perhaps a result of glucocorticoid deficiency in the central nervous system) to various degrees of hypertension with or without hypokalemic alkalosis or hyperandrogenism, or both, caused by increased cortisol and other salt-retaining steroids and adrenal androgens, respectively. In women, hyperandrogenism can result in acne, hirsutism, menstrual irregularities, oligoanovulation, and infertility; in men, it may lead to infertility and in children, to precocious puberty. Different molecular defects, such as point mutations or a microdeletion of the highly conserved glucocorticoid receptor gene, alter the functional characteristics or concentrations of the intracellular receptor and appear to cause glucocorticoid resistance. The extreme variability in the clinical manifestations of glucocorticoid resistance and its mimicry of many common diseases can be explained by the overall degree of glucocorticoid resistance, differing sensitivity of target tissues to mineralocorticoids or androgens or both, and perhaps different biochemical defects of the glucocorticoid receptor, with selective resistance of certain glucocorticoid responses in specific tissues. The various different symptoms of classic glucocorticoid resistance and the theoretical potential of this condition to appear surreptitiously emphasize the importance of the glucocorticoid receptor in the pathogenesis of human disease. RP CHROUSOS, GP (reprint author), NIH,BLDG 10,ROOM 10N262,BETHESDA,MD 20892, USA. NR 89 TC 167 Z9 173 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 1 PY 1993 VL 119 IS 11 BP 1113 EP 1124 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA MJ335 UT WOS:A1993MJ33500009 PM 8239231 ER PT J AU NISHIMURA, M MINGIOLI, E MCFARLIN, DE JACOBSON, S AF NISHIMURA, M MINGIOLI, E MCFARLIN, DE JACOBSON, S TI DEMONSTRATION OF HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I (HTLV-I) FROM AN HTLV-I SERONEGATIVE SOUTH INDIAN PATIENT WITH CHRONIC, PROGRESSIVE SPASTIC PARAPARESIS SO ANNALS OF NEUROLOGY LA English DT Note ID LEUKEMIA-VIRUS; SEQUENCES; DNA; AMPLIFICATION; RETROVIRUS; PROVIRUS AB Here we describe a human T-cell lymphotropic virus type I (HTLV-I) seronegative patient from South India with a chronic, progressive spastic paraparesis from which HTLV-I has been isolated from peripheral blood lymphocytes. HTLV-I pol and tax viral sequences were detected in DNA from fresh peripheral blood lymphocytes (PBL) by polymerase chain reaction (PCR) and liquid hybridization techniques. Southern blot analysis of the PCR products demonstrated a low copy number of HTLV-I at the level of one viral copy per 10,000 fresh PBL. A long-term CD4(+) T-cell line was established from PBL of this patient using recombinant interleukin-2, OKT3, and feeder cells. DNA from these cultured lines was amplified and portions of the HTLV-I long terminal repeat (U3), pol, env, and tax regions were sequenced (a total of 1,115 bp). The sequence data showed that the HTLV-I associated with this patient was 98.8% homologous to prototype HTLV-I. Southern blot analysis also confirmed the presence of full-length HTLV-I. These results indicate that HTLV-I can be demonstrated in an HTLV-I seronegative patient from South India with a chronic progressive neurological disorder. C1 NIH,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. NR 15 TC 11 Z9 12 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 1993 VL 34 IS 6 BP 867 EP 870 DI 10.1002/ana.410340618 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA MK474 UT WOS:A1993MK47400017 PM 8250538 ER PT J AU STONE, CD MCINTOSH, CL HENNEIN, HA MARON, BJ CLARK, RE AF STONE, CD MCINTOSH, CL HENNEIN, HA MARON, BJ CLARK, RE TI OPERATIVE TREATMENT OF PEDIATRIC OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY - A 26-YEAR EXPERIENCE SO ANNALS OF THORACIC SURGERY LA English DT Article ID AORTIC REGURGITATION; SUDDEN-DEATH AB We retrospectively reviewed the 26-year National Institutes of Health experience with operative treatment of obstructive hypertrophic cardiomyopathy in pediatric patients. Operative criteria were either severe obstructive symptoms (New York Heart Association functional class III or IV) or sudden death. Seventeen patients undenwent 19 open procedures, of which the present study is comprised. Complete follow-up was available 10.1 +/- 1.4 years (mean +/- standard error; range, 0.8 to 26.2 years) after operation. The mean ages at diagnosis and operation were 11.9 +/- 1.3 years (range, 1 to 17 years) and 14.8 +/- 0.7 years (range, 9 to 17 years), respectively. The preoperative intraventricular septum mean dimension was 23.2 +/- 1.3 mm (range, 11 to 36 mm). The left ventricular outflow tract gradient was 74 +/- 9 mm Hg (range, 20 to 175 mm Hg) at rest and 94 +/- 7 mm Hg (range, 55 to 175 mm Hg) with provocation. Fifteen patients (88%) underwent left ventricular myotomy and myectomy, and 2 underwent mitral valve replacement. Two patients who initially received left ventricular myotomy and myectomy later underwent mitral valve replacement. There were one perioperative death (6%) and five late sudden deaths (31%) at 3.8, 8.7, 9.6, 14.1, and 21 years postoperatively. Kaplan-Meier survival was 86% +/- 8% at 5 years and 77% +/- 12% at 10 years. After operation, the left ventricular outflow tract gradient decreased almost 80% to 21 +/- 15 mm Hg (p = 0.0001). In 8 patients, the left ventricular outflow tract gradient completely resolved. The New York Heart Association functional class was markedly improved (2.9 +/- 0.2 preoperatively to 1.1 +/- 0.1 postoperatively and 1.5 +/- 0.1 at 10.1 +/- 1.4 years; p = 0.0001). These data show that operative treatment of obstructive hypertrophic cardiomyopathy in children is safe and effective palliation. The high rate of late, and presumably arrhythmia-related, sudden death warrants close follow up with early aggressive treatment of arrhythmia. C1 NHLBI,SURG BRANCH,BETHESDA,MD 20892. NR 14 TC 10 Z9 10 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 DEC PY 1993 VL 56 IS 6 BP 1308 EP 1314 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA MP525 UT WOS:A1993MP52500013 PM 8267429 ER PT J AU TSYRLOV, IB GOLDFARB, IS GELBOIN, HV AF TSYRLOV, IB GOLDFARB, IS GELBOIN, HV TI ENZYME-KINETIC AND IMMUNOCHEMICAL CHARACTERISTICS OF MOUSE CDNA-EXPRESSED, MICROSOMAL, AND PURIFIED CYP1A1 AND CYP1A2 SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID 2 3-METHYLCHOLANTHRENE-INDUCIBLE FORMS; RAT-LIVER MICROSOMES; MONOCLONAL-ANTIBODIES; CYTOCHROME-P-450 ENZYMES; PURIFICATION; CYTOCHROMES-P-450; METABOLISM; ACTIVATION; ISOZYMES; CARCINOGENESIS RP TSYRLOV, IB (reprint author), NCI,MOLEC CARCINOGENESIS LAB,BLDG 37,ROOM 3E-20,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 54 TC 46 Z9 46 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 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD DEC PY 1993 VL 307 IS 2 BP 259 EP 266 DI 10.1006/abbi.1993.1588 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MM266 UT WOS:A1993MM26600006 PM 8274012 ER PT J AU THALMANN, I MACHIKI, K CALABRO, A HASCALL, VC THALMANN, R AF THALMANN, I MACHIKI, K CALABRO, A HASCALL, VC THALMANN, R TI URONIC ACID-CONTAINING GLYCOSAMINOGLYCANS AND KERATAN SULFATE ARE PRESENT IN THE TECTORIAL MEMBRANE OF THE INNER-EAR - FUNCTIONAL IMPLICATIONS SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID PROTEOGLYCANS; TRANSDUCTION; PROTEINS; ASSAY C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. UNIV TSUKUBA,TSUKUBA,IBARAKI 305,JAPAN. RP THALMANN, I (reprint author), WASHINGTON UNIV,SCH MED,DEPT OTOLARYNGOL,517 S EUCLID,ST LOUIS,MO 63110, USA. FU NIDCD NIH HHS [NIDCD DC 00384, NIDCD DC 01374, NIDCD DC 01414] NR 29 TC 32 Z9 32 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 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD DEC PY 1993 VL 307 IS 2 BP 391 EP 396 DI 10.1006/abbi.1993.1605 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MM266 UT WOS:A1993MM26600023 PM 8274027 ER PT J AU PENNEYS, NS LEONARDI, CL COOK, S BLAUVELT, A ROSENBERG, S EELLS, LD KONWISER, M AARONSON, CM AF PENNEYS, NS LEONARDI, CL COOK, S BLAUVELT, A ROSENBERG, S EELLS, LD KONWISER, M AARONSON, CM TI IDENTIFICATION OF MYCOBACTERIUM-TUBERCULOSIS DNA IN 5 DIFFERENT TYPES OF CUTANEOUS LESIONS BY THE POLYMERASE CHAIN-REACTION SO ARCHIVES OF DERMATOLOGY LA English DT Article ID LINKED IMMUNOSORBENT-ASSAY; CLINICAL SPECIMENS; RAPID DIAGNOSIS; AMPLIFICATION; COMPLEX; SAMPLES AB Background and Design: A spectrum of skin lesions are believed to be secondary to the presence of Mycobacterium tuberculosis. Demonstration of M tuberculosis directly or in culture in some of these eruptions can be difficult. We used the polymerase chain reaction and a primer/probe set specifically for M tuberculosis complex DNA to evaluate five types of skin lesions clinically considered to represent infection by, or reaction to, M tuberculosis. Observations: Mycobacterium tuberculosis DNA was demonstrated in paraffin-embedded sections of these five cases, representing a variety of clinical and histologic patterns. In two cases, M tuberculosis could not be demonstrated by routine cultural methods. Conclusion: DNA diagnostic methods such as the polymerase chain reaction can be used to rapidly identify cutaneous lesions produced by M tuberculosis. C1 UNIV MIAMI,DEPT DERMATOL,MIAMI,FL. NATL CANC INST,DERMATOL BRANCH,BETHESDA,MD. RP PENNEYS, NS (reprint author), ST LOUIS UNIV,SCH MED,DIV DERMATOL,1402 S GRAND BLVD,ST LOUIS,MO 63104, USA. NR 21 TC 34 Z9 35 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD DEC PY 1993 VL 129 IS 12 BP 1594 EP 1598 PG 5 WC Dermatology SC Dermatology GA MW826 UT WOS:A1993MW82600008 PM 8250581 ER PT J AU HALLETT, M LEBIEDOWSKA, MK THOMAS, SL STANHOPE, SJ DENCKLA, MB RAMSEY, J AF HALLETT, M LEBIEDOWSKA, MK THOMAS, SL STANHOPE, SJ DENCKLA, MB RAMSEY, J TI LOCOMOTION OF AUTISTIC ADULTS SO ARCHIVES OF NEUROLOGY LA English DT Article ID GAIT AB Objective: To assess gait in patients with autism. Design: Clinical and physiologic assessment. Setting: Research hospital. Patients and Subjects: Five adults with autism and five healthy, age-matched control subjects. Main Outcome Measure(s): Clinical and biomechanical assessment. Results: Clinical assessment showed mild clumsiness in four patients and upper limb posturing during gait in three patients. The velocity of gait, step length, cadence, step width, stance time, and vertical ground reaction forces were normal in all patients. The only significant abnormality was decreased range of motion of the ankle. Some patients exhibited slightly decreased knee flexion in early stance. Clinically, the gait appeared to be irregular in three patients, but the variability was not significantly increased. Conclusions: The findings in patients with autism indicate a nonspecific, neurological disturbance involving the motor system. The normal velocity of gait and the normal step length argue against a parkinsonian-type disturbance, whereas the clinical picture suggests a disturbance of the cerebellum. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT REHABIL MED,BIOMECH LAB,BETHESDA,MD 20892. JOHNS HOPKINS MED SCH,DEPT NEUROL,BALTIMORE,MD. NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892. RP HALLETT, M (reprint author), NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BLDG 10,ROOM 5N226,BETHESDA,MD 20892, USA. NR 14 TC 93 Z9 94 U1 0 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD DEC PY 1993 VL 50 IS 12 BP 1304 EP 1308 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA MX089 UT WOS:A1993MX08900005 PM 8257307 ER PT J AU MARCUS, SG MERINO, MJ GLATSTEIN, E DELANEY, TF STEINBERG, SM ROSENBERG, SA YANG, JC AF MARCUS, SG MERINO, MJ GLATSTEIN, E DELANEY, TF STEINBERG, SM ROSENBERG, SA YANG, JC TI LONG-TERM OUTCOME IN 87 PATIENTS WITH LOW-GRADE SOFT-TISSUE SARCOMA SO ARCHIVES OF SURGERY LA English DT Article ID RADIATION-THERAPY; DESMOID TUMORS; ADJUVANT CHEMOTHERAPY; CONSERVATIVE SURGERY; LOCAL RECURRENCE; LOWER-EXTREMITY; MANAGEMENT; SURVIVAL; RADIOTHERAPY; INSTITUTE AB Objective: To describe the long-term clinical outcome of patients with low-grade soft-tissue sarcoma and identify factors that may predict or determine their prognosis. Design: Retrospective chart review with multivariate analysis. Setting: Large research hospital and referral center. Patients: all patients treated between 1975 and 1990 at the National Cancer Institute (Bethesda, Md) who had a confirmed diagnosis of low-grade soft-tissue sarcoma. Interventions: Surgery and radiation therapy. Main Outcome Measures: Local recurrence and over-all survival. Results: For patients with nonretroperitoneal lesions, overall survival was excellent, with a history of recurrence, a positive surgical margin, and an absence of adjuvant radiation therapy significantly associated with increased risks of local recurrence. Patients with retroperitoneal lesions not only had an increased risk of local recurrence, but significantly poorer overall survival. Conclusions: Low-grade soft-tissue sarcomas are associated with excellent overall survival, especially those confined to nonretroperitoneal sites. The risk of local recurrence after resection with negative margins and/or adjuvant radiation therapy is very low and most recurrences can be controlled with further therapy. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NR 39 TC 31 Z9 31 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD DEC PY 1993 VL 128 IS 12 BP 1336 EP 1343 PG 8 WC Surgery SC Surgery GA MW448 UT WOS:A1993MW44800008 PM 8250705 ER PT J AU MARCUS, SG WALSH, TJ PIZZO, PA DANFORTH, DN AF MARCUS, SG WALSH, TJ PIZZO, PA DANFORTH, DN TI HEPATIC-ABSCESS IN CANCER-PATIENTS - CHARACTERIZATION AND MANAGEMENT SO ARCHIVES OF SURGERY LA English DT Article ID PYOGENIC LIVER-ABSCESS; PERCUTANEOUS DRAINAGE; FUNGAL-INFECTIONS; CANDIDIASIS; DIAGNOSIS; DISEASE AB Objective: To identify factors that may aid in the diagnosis and treatment of patients with malignant neoplasms in whom hepatic abscesses develop. Design: Retrospective review of medical records. Patients: Thirty-seven oncology patients in whom hepatic abscesses developed at the National Cancer Institute, Bethesda, Md, between June 1954 and October 1989. Results: Among 37 cancer patients, bacterial abscesses developed in 17 and fungal abscesses developed in 20. Among the patients with bacterial abscesses, 12 (71%) had a solid-tissue malignant neoplasm, 10 (59%) had a prior invasive procedure, and six (35%) had prior chemotherapy. In comparison, among the patients with fungal abscesses, 15 (75%) had a hematologic malignant neoplasm and five (25%) had a solid-tissue malignant neoplasm (P-2=.014). Two patients with fungal abscesses (10%) had a prior invasive procedure (P-2=.004) and 19 (95%) had prior chemotherapy (P-2<.0001). As compared with fungal abscesses, bacterial abscesses were larger (P-2<.00001) and fewer (P-2=.004). Antibiotics and percutaneous or surgical drainage effectively treated bacterial abscesses. Amphotericin B usually eradicated hepatic fungal infections. Conclusions: The results of this study reveal the importance of the clinical setting in the diagnosis of hepatic abscesses in cancer patients. Aggressive treatment of these abscesses is indicated and is frequently effective. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,INFECT DIS SECT,BETHESDA,MD 20892. NR 34 TC 30 Z9 30 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD DEC PY 1993 VL 128 IS 12 BP 1358 EP 1364 PG 7 WC Surgery SC Surgery GA MW448 UT WOS:A1993MW44800012 PM 8250709 ER PT J AU WEIFFENBACH, JM FOX, PC AF WEIFFENBACH, JM FOX, PC TI ODOR IDENTIFICATION ABILITY AMONG PATIENTS WITH SJOGRENS-SYNDROME SO ARTHRITIS AND RHEUMATISM LA English DT Note ID SMELL RP WEIFFENBACH, JM (reprint author), NIDR,BETHESDA,MD 20892, USA. NR 9 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 1993 VL 36 IS 12 BP 1752 EP 1754 DI 10.1002/art.1780361218 PG 3 WC Rheumatology SC Rheumatology GA ML262 UT WOS:A1993ML26200017 PM 8250997 ER PT J AU HAHN, SH GAHL, WA AF HAHN, SH GAHL, WA TI COPPER EFFECTS ON METAL REGULATORY FACTORS OF CULTURED HUMAN FIBROBLASTS SO BIOCHEMICAL MEDICINE AND METABOLIC BIOLOGY LA English DT Article ID METALLOTHIONEIN-I PROMOTER; TRANSCRIPTION FACTOR; NUCLEAR FACTOR; RESPONSIVE ELEMENTS; UPSTREAM SEQUENCES; DEPENDENT BINDING; IIA GENE; ENHANCER; INTERACTS; PROTEIN RP HAHN, SH (reprint author), NICHHD,HUMAN GENET BRANCH,HUMAN BIOCHEM GENET SECT,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 44 TC 2 Z9 2 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 0885-4505 J9 BIOCHEM MED METAB B PD DEC PY 1993 VL 50 IS 3 BP 346 EP 357 DI 10.1006/bmmb.1993.1075 PG 12 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA MM148 UT WOS:A1993MM14800010 PM 8123298 ER PT J AU AZARI, NP PIETRINI, P HORWITZ, B PETTIGREW, KD LEONARD, HL RAPOPORT, JL SCHAPIRO, MB SWEDO, SE AF AZARI, NP PIETRINI, P HORWITZ, B PETTIGREW, KD LEONARD, HL RAPOPORT, JL SCHAPIRO, MB SWEDO, SE TI INDIVIDUAL-DIFFERENCES IN CEREBRAL METABOLIC PATTERNS DURING PHARMACOTHERAPY IN OBSESSIVE-COMPULSIVE DISORDER - A MULTIPLE-REGRESSION DISCRIMINANT-ANALYSIS OF POSITRON EMISSION TOMOGRAPHIC DATA SO BIOLOGICAL PSYCHIATRY LA English DT Article DE OBSESSIVE-COMPULSIVE DISORDER; POSITRON EMISSION TOMOGRAPHY; DISCRIMINANT ANALYSIS; BRAIN; CLOMIPRAMINE FLUOXETINE; METABOLISM ID GLUCOSE-METABOLISM; BASAL GANGLIA; BRAIN-REGIONS; TRANSMISSION MEASUREMENTS; ALZHEIMERS-DISEASE; RATES; INTERCORRELATIONS; ADULTS; PET; HUNTINGTONS AB A multiple regression/discriminant analysis of positron emission tomographic cerebral metabolic (rCMRglc) data in 10 obsessive-compulsive disorder (OCD) patients before and during pharmacotherapy was carried out to see if rCMRglc interdependencies distinguished OCD patients from controls. Before therapy, a discriminant function reflecting parietal, sensorimotor, and midbrain rCMRglc interdependencies correctly classified eight (80%) of the 10 patients as OCD; after therapy, six (70%) were classified as controls, most of whom were responders. Before therapy, rCMRglc interdependencies involving basal ganglia, thalamus, limbic, and sensory and association cortical regions distinguished 67% of patients who clinically responded to drug (RESP, n = 6) and 75% of patients who did not (NRESP, n = 4)from controls. After therapy, all RESP were classified as controls; classification of NRESP remained unchanged. The results suggest the conjunctive utility of this method to assess individual differences in rCMRglc during pharmacotherapy, and to explore the neurobiology of OCD. C1 NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892. NIMH,DIV EPIDEMIOL,APPL & SERV RES,BETHESDA,MD 20892. RP AZARI, NP (reprint author), NIA,NEUROSCI LAB,BLDG 10,ROOM 6C414,BETHESDA,MD 20892, USA. NR 50 TC 21 Z9 21 U1 1 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 DEC 1 PY 1993 VL 34 IS 11 BP 798 EP 809 DI 10.1016/0006-3223(93)90069-P PG 12 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA MJ750 UT WOS:A1993MJ75000008 PM 8292684 ER PT J AU MERRILL, EW DENNISON, KA SUNG, C AF MERRILL, EW DENNISON, KA SUNG, C TI PARTITIONING AND DIFFUSION OF SOLUTES IN HYDROGELS OF POLY(ETHYLENE OXIDE) SO BIOMATERIALS LA English DT Article DE HYDROGELS; POLY(ETHYLENE) OXIDE; PARTITION; DIFFUSION ID SWOLLEN MEMBRANES; BEHAVIOR AB Hydrogels were created by electron beam irradiation of aqueous solutions of poly(ethylene oxide) (PEO) having a nominal molecular weight of 35000. The molecular weight between cross-links M(c) varied from 3000 to 15000, and the equilibrium volume fractions of polymer v2,s from 0.01 to 0.08. These hydrogels were exposed to aqueous solutions of solutes: tricyclic antidepressants, cyanocobalamin, four globular proteins and three linear species of PEO. Partition coefficients and diffusion coefficients were determined. For each solute the ratio diffusion coefficient in hydrogel/diffusion coefficient in free solution was determined, and related to the hydrogel parameters M(c) and v2,s and to the solute effective radius r(E) (Einstein radius). The diffusion coefficient ratio is greater for the flexible random coiling PEO than for the 'rigid' solutes at a given set of M(c), v2s and r(E), and the disparity increases rapidly as r(E) increases. Among the globular proteins the diffusion coefficient ratio decreases by orders of magnitude with small changes in r(E) (20.6-27.6 angstrom) and was found to be nearly zero for albumin (r(E) = 36.1 angstrom). The tricyclic antidepressants had partition coefficients of around 2, whereas the other solutes had partition coefficients of about unity. By reason of the partition coefficient of around 2, the diffusion coefficient ratio of a tricyclic antidepressant having a value of r(E) = 5.5 angstrom is half that of the larger cyanocobalamin, for which r(E) = 8.5 angstrom. C1 THREE M CO, ST PAUL, MN 55144 USA. NIH, BIOMED ENGN & INSTRUMENTAT PROGRAM, BETHESDA, MD 20892 USA. RP MIT, DEPT CHEM ENGN, CAMBRIDGE, MA 02139 USA. NR 17 TC 157 Z9 159 U1 4 U2 26 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 EI 1878-5905 J9 BIOMATERIALS JI Biomaterials PD DEC PY 1993 VL 14 IS 15 BP 1117 EP 1126 DI 10.1016/0142-9612(93)90154-T PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA MP264 UT WOS:A1993MP26400002 PM 8130315 ER PT J AU ORR, A PILCH, D HATCH, C IVANOVA, V BONNER, W AF ORR, A PILCH, D HATCH, C IVANOVA, V BONNER, W TI RAPID SCREENING OF RECOMBINANT CLONES SO BIOTECHNIQUES LA English DT Note C1 NCI,BLDG 37,RM 5D17,BETHESDA,MD 20892. NR 3 TC 0 Z9 0 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD DEC PY 1993 VL 15 IS 6 BP 984 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MK533 UT WOS:A1993MK53300006 PM 8292351 ER PT J AU MACKAY, AR GOMEZ, DE COTTAM, DW REES, RC NASON, AM THORGEIRSSON, UP AF MACKAY, AR GOMEZ, DE COTTAM, DW REES, RC NASON, AM THORGEIRSSON, UP TI IDENTIFICATION OF THE 72-KDA (MMP-2) AND 92-KDA (MMP-9) GELATINASE TYPE-IV COLLAGENASE IN PREPARATIONS OF LAMININ AND MATRIGEL(TM) SO BIOTECHNIQUES LA English DT Article ID SODIUM DODECYL-SULFATE; BASEMENT-MEMBRANE; PLASMINOGEN ACTIVATORS; POLYACRYLAMIDE GELS; CELL-ADHESION; MATRIX; PURIFICATION; COMPONENTS; PROTEINS; ANTIBODY AB EDTA inhibitable type IV collagenolytic activity copurified with laminin preparations from the Engelbreth-Holm-Swarm (EHS) tumor Several gelatinolytic and type IV collagenolytic matrix metalloproteinase (MMP) species were visualized in EHS laminin from three different sources by gelatin and type IV collagen substrate gel electrophoresis. Incubation with 4-aminophenylmercuric acetate and trypsin suggested that laminin contained both active and latent MMPs. EHS-derived reconstituted basement membrane, Matrigel(TM), was found to possess an MMP profile identical to that of laminin. The presence of 72-kDa (MMP-2) and 92-kDa (MMP-9) gelatinases/type IV collagenases was demonstrated in laminin nd Matrigel preparations by Western blot analysis. A rough quantitation of MMP-2 and MMP-9 in 30 mug of laminin and 100 mug of Matrigel was between 0.3 and 0.6 ng. The presence of these contaminants must be considered in experiments addressing the effects of EHS laminin or Matrigel on cell behavior and, in particular, stimulation of cellular proteolytic activity. C1 NCI,DIV CANC ETIOL,OFF DIRECTOR,BLDG 37,ROOM 2D-02,BETHESDA,MD 20892. UNIV SHEFFIELD,INST CANC STUDIES,SHEFFIELD S10 2TN,S YORKSHIRE,ENGLAND. OI Gomez, Daniel E/0000-0002-8629-0787 NR 26 TC 53 Z9 56 U1 0 U2 4 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD DEC PY 1993 VL 15 IS 6 BP 1048 EP 1051 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MK533 UT WOS:A1993MK53300015 PM 8292337 ER PT J AU SPANGRUDE, GJ BROOKS, DM AF SPANGRUDE, GJ BROOKS, DM TI MOUSE STRAIN VARIABILITY IN THE EXPRESSION OF THE HEMATOPOIETIC STEM-CELL ANTIGEN LY-6A/E BY BONE-MARROW CELLS SO BLOOD LA English DT Article ID ACTIVATING PROTEIN; MULTIGENE FAMILY; LYMPHOCYTE-ACTIVATION; CDNA CHARACTERIZATION; SUBSETS; TAP; POPULATIONS; STIMULATION; ANTIBODIES; MOLECULES RP SPANGRUDE, GJ (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS,903 S 4TH ST,HAMILTON,MT 59840, USA. NR 36 TC 130 Z9 133 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 1993 VL 82 IS 11 BP 3327 EP 3332 PG 6 WC Hematology SC Hematology GA MJ708 UT WOS:A1993MJ70800015 PM 8241503 ER PT J AU HEYES, MP SAITO, K MAJOR, EO MILSTIEN, S MARKEY, SP VICKERS, JH AF HEYES, MP SAITO, K MAJOR, EO MILSTIEN, S MARKEY, SP VICKERS, JH TI A MECHANISM OF QUINOLINIC ACID FORMATION BY BRAIN IN INFLAMMATORY NEUROLOGICAL DISEASE - ATTENUATION OF SYNTHESIS FROM L-TRYPTOPHAN BY 6-CHLOROTRYPTOPHAN AND 4-CHLORO-3-HYDROXYANTHRANILATE SO BRAIN LA English DT Article ID INFECTED RHESUS MACAQUES; CEREBROSPINAL-FLUID; KYNURENIC ACID; RAT-BRAIN; INDOLEAMINE 2,3-DIOXYGENASE; HUNTINGTONS-DISEASE; 3-HYDROXYANTHRANILIC ACID; NEUROACTIVE KYNURENINES; INTERFERON-GAMMA; NEURONAL DEGENERATION AB Quinolinic acid (QUIN), kynurenic acid (KYNA) and L-kynurenine (L-KYN) are neuroactive kynurenine pathway metabolites that accumulate in inflammatory neurological diseases. These increases were attributed to the induction of indoleamine-2,3-dioxygenase (IDO), the enzyme that converts L-tryptophan into L-KYN. Direct conversion of L-tryptophan into QUIN by brain tissue occurs in conditions of CNS inflammation, but not by normal brain tissue. To investigate whether increased activity of enzymes distal to IDO may determine L-KYN conversion to QUIN, rhesus macaques were inoculated with poliovirus directly into the spinal cord, as a model of focal inflammatory neurological disease (FASEB J. 6, 2977-2989, 1992). Induction of spinal cord IDO (35.9-fold) accompanied smaller, but proportional increases in kynurenine-3-hydroxylase (2.4-fold) and kynureninase (2.3-fold) activities, which were correlated to CSF and tissue QUIN levels, as well as to measures of inflammatory lesions. 3-Hydroxyanthranilate-3,4-dioxygenase activity was unchanged. Cerebrospinal fluid KYNA levels increased in proportion to both IDO activity and L-KYN accumulation, though kynurenine aminotransferase activity was unaffected. Cerebrospinal fluid neopterin, a marker of macrophage and immune activation, accumulated in proportion to the responsive enzymes and metabolites. The cell types involved in producing QUIN were investigated in vitro. Human foetal brain cultures consisting of astrocytes and neurons converted large quantities of [C-13(6)]L-tryptophan into L-KYN when stimulated by gamma-interferon, but very little [C-13(6)]QUIN was formed unless macrophages (THP-1 cells) were first added to the cultures (to model a key component of brain inflammation). [C-13(6),]L-Tryptophan was converted into [C-13(6)]QUIN by either gamma-interferon stimulated macrophages, or following intracisternal administration into poliovirus-infected macaques. Inhibitors of the kynurenine pathway, 6-chlorotryptophan and 4-chloro-3-hydroxyanthranilic acid, attenuated [C-13(6)],QUIN formation by macrophages, and when co-infused with [C-13(6)]L-tryptophan into poliovirus-infected macaques. These results suggest roles for increased activities of IDO, kynurenine-3-hydroxylase and kynureninase in accelerating the synthesis of QUIN, L-KYN and KYNA in conditions of brain inflammation. Macrophage infiltrates, and perhaps microglia, are important sources of QUIN, whereas constitutive brain cells and macrophages are sources of L-KYN. Drugs that inhibit kynurenine pathway enzymes attenuate QUIN formation in the CNS, and provide tools to examine the consequences of reduced QUIN accumulation. C1 NIMH, NEUROCHEM LAB, BETHESDA, MD 20892 USA. NINCDS, VIRAL & MOLEC PATHOGENESIS LAB, BETHESDA, MD 20892 USA. US FDA, CTR BIOL EVALUAT & RES, PATHOBIOL & PRIMATOL LAB, BETHESDA, MD USA. RP HEYES, MP (reprint author), NIMH, CLIN SCI LAB, ANALYT BIOCHEM SECT, BLDG 10, ROOM 3D40, BETHESDA, MD 20892 USA. NR 90 TC 126 Z9 128 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD DEC PY 1993 VL 116 BP 1425 EP 1450 PN 6 PG 26 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA MW136 UT WOS:A1993MW13600008 PM 8293279 ER PT J AU LIEBMANN, JE COOK, JA LIPSCHULTZ, C TEAGUE, D FISHER, J MITCHELL, JB AF LIEBMANN, JE COOK, JA LIPSCHULTZ, C TEAGUE, D FISHER, J MITCHELL, JB TI CYTOTOXIC STUDIES OF PACLITAXEL (TAXOL) IN HUMAN TUMOR-CELL LINES SO BRITISH JOURNAL OF CANCER LA English DT Article ID PHASE-I; AGENT; RESISTANCE; DRUGS; TRIAL AB The cytotoxicity of paclitaxel against eight human tumour cell lines has been studied with in vitro clonogenic assays. The fraction of surviving cells fell sharply after exposure for 24 h to paclitaxel concentrations ranging from 2 to 20 nm; the paclitaxel IC50 Was found to range between 2.5 and 7.5 nm. Increasing the paclitaxel concentration above 50 nm, however, resulted in no additional cytotoxicity after a 24 h drug exposure. Cells incubated in very high concentrations of paclitaxel (10,000 nm) had an increase in survival compared with cells treated with lower concentrations of the drug. Prolonging the time of exposure of cells to paclitaxel from 24 to 72 h increased cytotoxicity from 5 Lo 200 fold in different cell lines. Exponentially growing cells were more sensitive to paclitaxel than were cells in the plateau phase of growth. Cremophor EL, the diluent in which the clinical preparation of paclitaxel is formulated, antagonised paclitaxel at concentrations of 0.135% (v/v). These data suggest that paclitaxel will be most effective clinically when there is prolonged exposure of tumour to the drug. Further, it appears that modest concentrations (i.e., 50 nm) should be as effective as higher concentrations of paclitaxel. Finally, we have noted that Cremophor EL is a biologically active diluent and, at high concentrations (0.135% v/v), can antagonise paclitaxel cytotoxicity. RP LIEBMANN, JE (reprint author), NCI,RADIAT ONCOL BRANCH,BLDG 10,ROOM B3B69,BETHESDA,MD 20892, USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 23 TC 273 Z9 280 U1 1 U2 24 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD DEC PY 1993 VL 68 IS 6 BP 1104 EP 1109 DI 10.1038/bjc.1993.488 PG 6 WC Oncology SC Oncology GA MK531 UT WOS:A1993MK53100008 PM 7903152 ER PT J AU TRIMBLE, EL UNGERLEIDER, RS ABRAMS, JA KAPLAN, RS FEIGAL, EG SMITH, MA CARTER, CL FRIEDMAN, MA AF TRIMBLE, EL UNGERLEIDER, RS ABRAMS, JA KAPLAN, RS FEIGAL, EG SMITH, MA CARTER, CL FRIEDMAN, MA TI NEOADJUVANT THERAPY IN CANCER-TREATMENT SO CANCER LA English DT Article; Proceedings Paper CT 2nd national conference on new oncologic agents : Practical applications CY FEB 04-06, 1993 CL SAN DIEGO, CA SP AMER CANC SOC, AMER COLL SURGEONS, COMMISS CANC, AMER SOC CLIN ONCOL, AMER SOC PREVENT ONCOL, ONCOL NURSING SOC ID SQUAMOUS-CELL CARCINOMA; SOFT-TISSUE SARCOMAS; PHASE-II TRIAL; BREAST-CANCER; ADJUVANT CHEMOTHERAPY; OSTEOGENIC-SARCOMA; PREOPERATIVE CHEMOTHERAPY; CONSERVATIVE TREATMENT; RADIATION-THERAPY; EWINGS-SARCOMA AB Neoadjuvant therapy has come to play an increasingly prominent role in the treatment of cancer. Originally defined as systemic therapy given before local treatment, the concept has been extended to include radiation therapy given before surgery. Potential advantages include improved local and distant control, direct evaluation, and organ-sparing treatment. Potential disadvantages include increased toxicity and cost, potential delay in effective treatment, and obscuring of pathologic staging. Neoadjuvant therapy in cancer treatment may be viewed in three categories: tumors in which neoadjuvant treatment has been shown effective, thus becoming standard therapy; tumors in which it has been shown to facilitate organ-sparing, and tumors in which its utility has not been shown. For patients with osteogenic sarcoma, for example, preoperative chemotherapy and limb salvage therapy have become the standard of care. Response to chemotherapy, ascertained by histologic review of the surgical specimen, can be used to tailor postoperative chemotherapy. In patients with advanced laryngeal squamous cell carcinoma, neoadjuvant chemotherapy followed by radiation has permitted laryngeal preservation in a majority of patients without compromising overall survival. Phase II and III studies conducted in women with breast cancer have demonstrated promising results for neoadjuvant chemotherapy given before radiation therapy and/or surgery. Phase III studies to compare neoadjuvant therapy to standard therapy in patients with breast cancer are underway. For neoadjuvant therapy, as with other innovations in cancer treatment, it is crucial that a new strategy must be compared closely to standard therapy in terms of recurrence, survival, and impact on organ sparing, as well as quality of life and treatment costs. C1 EMMES CORP,POTOMAC,MD. RP TRIMBLE, EL (reprint author), NCI,6130 EXECUT BLVD,SUITE 741,ROCKVILLE,MD 20852, USA. NR 48 TC 18 Z9 21 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD DEC 1 PY 1993 VL 72 IS 11 SU S BP 3515 EP 3524 DI 10.1002/1097-0142(19931201)72:11+<3515::AID-CNCR2820721619>3.0.CO;2-A PG 10 WC Oncology SC Oncology GA ML143 UT WOS:A1993ML14300017 PM 8242583 ER PT J AU DELAPENA, LB PYRON, S NICHOLS, J AF DELAPENA, LB PYRON, S NICHOLS, J TI TAXOL - A CASE-STUDY SO CANCER NURSING LA English DT Article DE TAXOL; CASE REPORT ID PHASE-I TRIAL; ANTITUMOR AGENTS; CELL-LINES; MICROTUBULES; INFUSION; TAXOTERE; CANCER; CISPLATIN; CARCINOMA; MECHANISM AB Taxol is a novel antineoplastic agent that has demonstrated significant activity in ovarian carcinoma. Clinical trials are now underway to determine its use in combination with other chemotherapeutic agents, cytokines, and other cancers. The purpose of this article is to review clinical trials using Taxol and relevant nursing care for patients receiving this drug. The nursing implications for Taxol's administration, side effects, and toxicities are also presented. Knowledge of Taxol allows the nurse to provide optimal nursing care and to create appropriate patient care and teaching plans. C1 NIH,CTR CLIN,INST CANC NURSING,BETHESDA,MD. NIH,CTR CLIN,HEART LUNG & BLOOD NURSING SERV,BETHESDA,MD. RP DELAPENA, LB (reprint author), NIH,CTR CLIN,CANC NURSING SERV,BLDG 10,ROOM 7D-37,BETHESDA,MD 20892, USA. NR 47 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD DEC PY 1993 VL 16 IS 6 BP 423 EP 430 PG 8 WC Oncology; Nursing SC Oncology; Nursing GA MP582 UT WOS:A1993MP58200001 PM 7906612 ER PT J AU LAKE, T JENKINS, J AF LAKE, T JENKINS, J TI CANCER-CHEMOTHERAPY - CLINICAL-TRIALS SO CANCER NURSING LA English DT Article RP LAKE, T (reprint author), NIH,CANC NURSE SERV,BETHESDA,MD 20892, USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD DEC PY 1993 VL 16 IS 6 BP 486 EP 497 PG 12 WC Oncology; Nursing SC Oncology; Nursing GA MP582 UT WOS:A1993MP58200010 PM 8111754 ER PT J AU FINKE, JH ZEA, AH STANLEY, J LONGO, DL MIZOGUCHI, H TUBBS, RR WILTROUT, RH O'SHEA, JJ KUDOH, S KLEIN, E BUKOWSKI, RM OCHOA, AC AF FINKE, JH ZEA, AH STANLEY, J LONGO, DL MIZOGUCHI, H TUBBS, RR WILTROUT, RH O'SHEA, JJ KUDOH, S KLEIN, E BUKOWSKI, RM OCHOA, AC TI LOSS OF T-CELL RECEPTOR ZETA-CHAIN AND P56(LCK) IN T-CELLS INFILTRATING HUMAN RENAL-CELL CARCINOMA SO CANCER RESEARCH LA English DT Note ID TUMOR-BEARING MICE; LYMPHOCYTES-T; EXPRESSION; IMMUNOTHERAPY; MELANOMA AB Cancer patients and mice bearing tumors develop a progressive immunosuppression manifested by a decreased delayed-type hypersensitivity, decreased T-cell lytic activity diminished production of lymphokines, and a reduced T-cell proliferative response. The mechanisms underlying these changes are incompletely understood. We recently reported the presence of marked alterations in signal transduction in T-cells from mice bearing long-term (28-day) tumors. We hypothesized that a soluble product produced by the tumor or resulting from the immune response to tumor might be responsible for inducing the changes in T-cells. Tumor-infiltrating lymphocytes from patients with renal cell carcinoma tested here showed, in 10 of 11 cases, a marked decrease in the expression of the T-cell receptor zeta chain and in p56lck tyrosine kinase. The presence of major alterations in the tumor-infiltrating lymphocytes with only minor changes in the peripheral blood leukocyte T-cells supports the notion that the defects are induced by exposure to tumor. These results suggest that tumor-infiltrating lymphocytes may be compromised in their antitumor efficacy in patients with renal cell cancer. C1 NCI, FCRDC,PROGRAM RESOURCES INC DYNCORP, PROGRAM RESOURCES,IMMUNOTHERAPY LAB,POB B, FREDERICK, MD 21702 USA. NCI, FCRDC, DIV CANC TREATMENT, BIOL RESPONSE MODIFIERS PROGRAM, FREDERICK, MD 21702 USA. CLEVELAND CLIN EDUC FDN, DEPT IMMUNOL, CLEVELAND, OH 44106 USA. CLEVELAND CLIN EDUC FDN, DEPT PATHOL, CLEVELAND, OH 44106 USA. CLEVELAND CLIN EDUC FDN, DEPT UROL, CLEVELAND, OH 44106 USA. CLEVELAND CLIN EDUC FDN, EXPTL THERAPEUT PROGRAM, CLEVELAND, OH 44106 USA. FU NCI NIH HHS [CA 48919, CA56937]; PHS HHS [N01-C0-74102] NR 19 TC 395 Z9 402 U1 0 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 DEC 1 PY 1993 VL 53 IS 23 BP 5613 EP 5616 PG 4 WC Oncology SC Oncology GA MJ268 UT WOS:A1993MJ26800009 PM 8242613 ER PT J AU CROPP, CS CHAMPEME, MH LIDEREAU, R CALLAHAN, R AF CROPP, CS CHAMPEME, MH LIDEREAU, R CALLAHAN, R TI IDENTIFICATION OF 3 REGIONS ON CHROMOSOME-17Q IN PRIMARY HUMAN BREAST CARCINOMAS WHICH ARE FREQUENTLY DELETED SO CANCER RESEARCH LA English DT Note ID PROTO-ONCOGENE; OVARIAN-CANCER; MUTATIONS; GENE AB We have examined the long arm of chromosome 17 in sporadic breast carcinomas for the loss of heterozygosity (LOH) at 18 polymorphic loci. At least three distinct regions could be identified by the frequency of LOH and confirmed by high density deletion maps of individual tumor DNAs. A proximal region affected by LOH is located in a 22-cM region defined by D17S73 and NME1 and thus is similar in location to the region thought to contain the BRCA1 gene associated with familial breast and breast/ovarian cancer. The central region affected by LOH is bordered by the D17S86 and D17S21 loci and is estimated to be 28 cM in size. The third region is bordered by the D17S20 and D17S77 loci which are 11 cM apart. These results define three independent regions of chromosome 17q which are likely to contain tumor suppressor genes relevant to the etiology of sporadic breast carcinoma. C1 NCI,TUMOR IMMUNOL & BIOL,BLDG 10,ROOM 5B50,BETHESDA,MD 20892. CTR RENE HUGUENIN,INSERM,F-92211 ST CLOUD,FRANCE. NR 18 TC 93 Z9 93 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 1993 VL 53 IS 23 BP 5617 EP 5619 PG 3 WC Oncology SC Oncology GA MJ268 UT WOS:A1993MJ26800010 PM 8242614 ER PT J AU JUNGHANS, RP DOBBS, D BRECHBIEL, MW MIRZADEH, S RAUBITSCHEK, AA GANSOW, OA WALDMANN, TA AF JUNGHANS, RP DOBBS, D BRECHBIEL, MW MIRZADEH, S RAUBITSCHEK, AA GANSOW, OA WALDMANN, TA TI PHARMACOKINETICS AND BIOACTIVITY OF 1,4,7,10-TETRA-AZACYLODODECANE N,N',N'',N'''-TETRAACETIC ACID (DOTA)-BISMUTH-CONJUGATED ANTI-TAC ANTIBODY FOR ALPHA-EMITTER (BI-212) THERAPY SO CANCER RESEARCH LA English DT Article ID MONOCLONAL-ANTIBODY; T-CELLS; RADIOIMMUNOTHERAPY; MODEL; IMMUNOTHERAPY; INDUCTION; RECEPTOR; KINETICS; TOXICITY; RAT AB A major factor that is critical to the potential effectiveness of alpha-emitter Bi-212 radioimmunotherapy is the design of radiometal-chelated antibodies that will be stable in vivo. The chelate should bind the radiometal firmly to minimize release of the radionuclide from the monoclonal antibody-chelate complex. The present study examines a member of a new class of polyamine carboxylate chelating compounds, the DOTA ligands, for conjugating radiometal ions to antibody. Biocompatibility and stability are assessed with the anti-Tac monoclonal antibody that is directed against the human interleukin 2 receptor. The scientific basis for the clinical use of this antibody in radioimmunotherapy is that resting normal cells do not express the interleukin 2 receptor, whereas the receptor is expressed on the surface of certain neoplasms and by activated T-cells in select autoimmune diseases and in allograft rejection. First, we examined the impact of the labeling procedure and the presence of the chelate, DOTA, on antibody bioavailability and survival. Next, we studied the capacity of the antibody-chelate complex to retain radiobismuth. Coupling DOTA to antibody or adding Bi(III) to DOTA-coupled antibody did not disturb antibody immunoreactivity in in vitro binding studies. In addition, as analyzed by in vivo studies, DOTA-antibody dummy labeled with nonradioactive bismuth showed pharmacokinetics and tissue distribution identical to those of antibody not modified with DOTA. DOTA-anti-Tac charged with radioactive bismuth showed pharmacokinetics identical to radioiodinated dummy-labeled DOTA-antibody, suggesting little premature release of radioactive bismuth from the antibody complex. Moreover, in the early, therapeutically relevant time points (2 h and 6 h), there was no significant preferential accumulation of bismuth in any organ. At the 5-day time point, beyond the range of therapeutic interest, there was delayed excretion of bismuth from reticuloendothelial tissues relative to radioiodine from catabolized antibody. Excretion of catabolized DOTA-bismuth had an apparent t1/2 of approximately 1 day without the marked renal accumulation typical of the free bismuth ion. The compatibility of DOTA conjugation with antibody bioactivity and the stability of the radioactive bismuth complex in vivo provide important preclinical validation of the potential utility of this new chelating agent for Bi-212 monoclonal antibody radioimmunotherapy in humans. C1 NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NCI,METAB BRANCH,BETHESDA,MD 20892. RP JUNGHANS, RP (reprint author), HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,DEPT HEMATOL ONCOL,185 PILGRIM RP,BOSTON,MA 02215, USA. NR 31 TC 34 Z9 35 U1 2 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 1993 VL 53 IS 23 BP 5683 EP 5689 PG 7 WC Oncology SC Oncology GA MJ268 UT WOS:A1993MJ26800022 PM 8242624 ER PT J AU ZHANG, H COONEY, DA ZHANG, MH AHLUWALIA, G FORD, H JOHNS, DG AF ZHANG, H COONEY, DA ZHANG, MH AHLUWALIA, G FORD, H JOHNS, DG TI RESISTANCE TO CYCLOPENTENYLCYTOSINE IN MURINE LEUKEMIA-L1210 CELLS SO CANCER RESEARCH LA English DT Article ID CTP SYNTHETASE; CYTOSINE; INVITRO; TRIPHOSPHATE; ANTITUMOR; KINASE AB Cyclopentenyl cytosine (CPEC) exhibits oncological activity in murine and human tumor cells and has now entered Phase I clinical trials. Its mode of action as an antitumor agent appears to be inhibition by its triphosphate (CPEC-TP) of CTP synthase, the enzyme which converts UTP to CTP. In an attempt to elucidate the mechanism of resistance to CPEC, a murine leukemia cell line resistant to CPEC (L1210/CPEC) was developed by N-methyl-N-nitro-N-nitrosoguanidine-induced mutagenesis and subsequent selection by cultivation of the L1210 cells in the presence of 2 muM CPEC. Resistant clones were maintained in CPEC-free medium for 6 generations before biochemical studies were performed. The resistant clone selected for further studies was approximately 13,000-fold less sensitive to growth inhibition by CPEC than the parental cells, and the concentration of CPEC required to deplete CTP in the resistant cells was 50-fold higher than in the sensitive cells. A comparison of the kinetic properties of CTP synthase from sensitive and resistant cells indicated alteration in the properties of the enzyme from the latter; the median inhibitory concentration for CPEC-TP increased from 2 to 14 muM, K(m) for UTP decreased from 126 to 50 muM, and V(max) increased 12-fold from 0.2 to 2.3 nmol/mg/min. Northern blot analyses of polyadenylated RNA from the resistant and sensitive cells indicated a 3-fold increase in transcripts of the CTP synthase gene in the resistant line. Consistent with these alterations in the properties of the enzyme, the resistant cells exhibited significantly expanded CTP and dCTP pools (4-5-fold) when compared with the sensitive cells. No change was observed, however, in the properties of uridine-cytidine kinase, the enzyme responsible for the initial phosphorylation of CPEC; despite this, however, cellular uptake of CPEC was greatly decreased, and phosphorylation of CPEC and its incorporation into RNA were 10-fold less than in the parental cells. These latter observations are most readily explained by feedback inhibition by the increased CTP levels of the resistant cells of uridine-cytidine kinase and/or of the membrane transport process used for initial entry of CPEC. RP ZHANG, H (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BLDG 37,ROOM 5B22,BETHESDA,MD 20892, USA. NR 19 TC 21 Z9 21 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 1993 VL 53 IS 23 BP 5714 EP 5720 PG 7 WC Oncology SC Oncology GA MJ268 UT WOS:A1993MJ26800026 PM 7694793 ER PT J AU SNYDERWINE, EG BUONARATI, MH FELTON, JS TURTELTAUB, KW AF SNYDERWINE, EG BUONARATI, MH FELTON, JS TURTELTAUB, KW TI METABOLISM OF THE FOOD-DERIVED MUTAGEN CARCINOGEN 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE (PHIP) IN NONHUMAN-PRIMATES SO CARCINOGENESIS LA English DT Article ID COOKED FOOD; HETEROCYCLIC AMINES; BORNE CARCINOGEN; LIVER-MICROSOMES; PYRIDINE PHIP; RAT-LIVER; ACTIVATION; DNA; IDENTIFICATION; BEEF AB Metabolism of the food-derived heterocyclic amine mutagen/ carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) was examined in cynomolgus monkeys. [H-3]PhIP (50 mu mol/kg, p.o) was extensively metabolized, with only 1% of the dose excreted into the urine as parent compound. Four metabolites were isolated by HPLC and identified: PhIP-4'-O-glucuronide, PhIP-4'-sulfate, 4'-hydroxy-PhIP and a glucuronide conjugate of N-hydroxy-PhIP. All four metabolites were detected in urine, bile and plasma of monkeys. 4'-Hydroxy-PhIP and PhIP were found in feces. The major PhIP metabolite in urine, bile and plasma was PhIP-4'-sulfate. In urine this metabolite constituted similar to 64-72% of the radioactivity excreted. The clearance of PhIP and PhIP metabolites from plasma was rapid, with the largest elimination occurring within 8 h. Administration of nine consecutive daily doses of unlabeled PhIP (50 mu mol/kg, p.o.) prior to administration of [H-3]PhIP (50 mu mol/kg, p.o.) did not alter the plasma clearance of radiolabeled PhIP or PhIP metabolites, suggesting that this multiple-dose regimen did not induce or alter PhIP metabolism. PhIP formed DNA adducts in white blood cells, as determined by the P-32-postlabeling method. The levels of PhIP-DNA adducts in blood appeared to peak 3 h after administering a single dose of PhIP (50 mu mol/kg, p.o.) and were still detected 1 week after dosing. The presence of the glucuronide conjugate of N-hydroxy-PhIP in urine, bile and plasma, and the presence of PhIP-DNA adducts in white blood cells indicate that PhIP undergoes metabolic activation via N-hydroxylation in cynomolgus monkeys. The results suggest that PhIP is activated in vivo to genotoxic metabolites in nonhuman primates and thus is a potential carcinogen in this species. C1 LAWRENCE LIVERMORE NATL LAB,BIOL & BIOTECHNOL RES PROGRAM,LIVERMORE,CA 94551. RP SNYDERWINE, EG (reprint author), NCI,DIV CANC ETIOL,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA 55861-01] NR 38 TC 23 Z9 23 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 1993 VL 14 IS 12 BP 2517 EP 2522 DI 10.1093/carcin/14.12.2517 PG 6 WC Oncology SC Oncology GA MN311 UT WOS:A1993MN31100012 PM 8269621 ER PT J AU ESPOSITO, M VANNOZZI, MO VIALE, M FULCO, RA COLLECCHI, P MERLO, F DECIAN, F ZICCA, A CADONI, A POIRIER, MC AF ESPOSITO, M VANNOZZI, MO VIALE, M FULCO, RA COLLECCHI, P MERLO, F DECIAN, F ZICCA, A CADONI, A POIRIER, MC TI PARA-AMINOBENZOIC ACID SUPPRESSION OF CIS-DIAMMINEDICHLOROPLATINUM(II) NEPHROTOXICITY SO CARCINOGENESIS LA English DT Article ID OVARIAN-CANCER; DNA; CISPLATIN; PLATINUM; CHEMOTHERAPY; CIS-DICHLORODIAMMINEPLATINUM(II); SPECTROMETRY; CELLS AB Concurrent administration of para-aminobenzoic acid (PABA) reduced the toxicity of cis-diamminedichloroplatinum(II) (DDP) in a dose-related manner in rats. When administered i.p. simultaneously with 7.5 mg/kg DDP, PABA (100 mg/kg) significantly reduced plasma urea nitrogen (PUN) and plasma creatinine levels as well as DDP-induced weight loss. Increasing doses of PABA (25, 50 and 100 mg/kg) correlated with progressively better parameters of renal activity and body wt and with lower levels of platinum in plasma and tissues ire rats killed 5 days after drug administration. The formation of cisplatin - DNA adducts, the total platinum levels in kidney and testes and the DDP-induced tumor response were investigated in the presence and absence of PABA exposure in mice bearing P388 leukemic cells. Renal and testicular DNA-adducts in mice treated i.p. with 16 mg/kg DDP in normal saline were higher than those observed in mice receiving the same protocol and added PABA. Analysis of tissue platinum content demonstrated significantly lower platinum levels both in kidneys (P < 0.05) and testes (P < 0.01) of mice receiving DDP and PABA in normal saline compared to those receiving only DDP in normal saline. PABA did not affect the in vivo and in vitro antitumor activity of DDP against P388 leukemia, and there was no significant PABA-induced modification in the concentration of platinum both in the tumor cells and in DNA samples isolated from P388 leukemic cells of DDP-treated mice. We conclude that PABA may be a promising compound far reducing DDP-toxic side effects, including nephrotoxicity, without compromising its antitumor activity. C1 UNIV GENOA,IST NAZL RIC CANC,SERV EPIDEMIOL AMBIENTALE & BIOSTAT,GENOA,ITALY. UNIV GENOA,IST PATOL CHIRURG,GENOA,ITALY. UNIV GENOA,IST ANAT UMANA,GENOA,ITALY. NCI,DIV CANC ETIOL,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. RP ESPOSITO, M (reprint author), UNIV GENOA,IST NAZL RIC CANC,SERV FARMACOL TOSSICOL,GENOA,ITALY. NR 20 TC 12 Z9 14 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 1993 VL 14 IS 12 BP 2595 EP 2599 DI 10.1093/carcin/14.12.2595 PG 5 WC Oncology SC Oncology GA MN311 UT WOS:A1993MN31100026 PM 8269632 ER PT J AU MILLS, KJ REYNOLDS, SH SMART, RC AF MILLS, KJ REYNOLDS, SH SMART, RC TI DIACYLGLYCEROL IS AN EFFECTOR OF THE CLONAL EXPANSION OF CELLS CONTAINING ACTIVATED HA-RAS GENES SO CARCINOGENESIS LA English DT Note ID PROTEIN-KINASE-C; MOUSE SKIN CARCINOGENESIS; TUMOR PROMOTION; PHORBOL ESTER; BENIGN-TUMORS; FATTY-ACID; 12-O-TETRADECANOYLPHORBOL-13-ACETATE; SN-1,2-DIACYLGLYCEROLS; SN-1,2-DIDECANOYLGLYCEROL; PHOSPHOLIPIDS AB Diacylglycerols (DAG) are lipid second messengers which are generated during phospholipase-catalyzed hydrolysis of phospholipids. The model DAG, sn-1,2-didecanoylglycerol (DIC10), is an effective topical tumor promoter in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mouse skin. We now report that 11/12 of DMBA-initiated/DIC10-promoted papillomas examined contain an A --> T mutation in the 61st codon of the Ha-ras gene, suggesting that DAGs affect the clonal expansion of activated Ha-ras-containing cells. To explore further the DIC10-induced clonal expansion of activated Ha-ras-containing cells, we have examined the tumor-promoting effect of DIC10 in tale skin of transgenic TG.AC mice, which harbor a v-Ha-ras transgene. By 9 weeks of promotion, 100% of the TG.AC mice developed squamous papillomas and by 15 weeks these mice developed >20 papillomas/mouse. Because fatty acids are known to participate in signal transduction pathways, and since cellular lipases could cleave the fatty acid side chains present in DIC10, we have examined the tumor promoting activity of n-decanoic acid to verify the specificity of promotional activity of DIC10. n-Decanoic acid did not function as a tumor promoter. These data implicate BAG as an effector of the clonal expansion of mutated Ha-ras-containing cells, and support a mechanism whereby an increase in endogenous BAG could contribute to the clonal: expansion of cells containing a Ha-ras oncogene. C1 N CAROLINA STATE UNIV,DEPT TOXICOL,RALEIGH,NC 27695. NIEHS,RES TRIANGLE PK,NC 27709. FU NCI NIH HHS [NCI CA46637] NR 30 TC 13 Z9 13 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 1993 VL 14 IS 12 BP 2645 EP 2648 DI 10.1093/carcin/14.12.2645 PG 4 WC Oncology SC Oncology GA MN311 UT WOS:A1993MN31100035 PM 8269640 ER PT J AU OSTROWSKI, LE GRAY, TE RANDELL, SH NETTESHEIM, P AF OSTROWSKI, LE GRAY, TE RANDELL, SH NETTESHEIM, P TI CHARACTERIZATION OF A 3RD TRANSFORMING GROWTH-FACTOR BETA(1) TRANSCRIPT IN RAT TRACHEAL EPITHELIAL-CELLS SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID TGF-BETA; FACTOR-BETA-1 GENE; MESSENGER-RNA; EXPRESSION; PROMOTER; RESPONSIVENESS; PROLIFERATION; REGENERATION; STIMULATION; ACTIVATION AB It has been previously reported (R. W. Steigerwalt et al., Mol. Carcinog., 5: 32-40, 1992) that primary cultures of rat tracheal epithelial (RTE) cells and immortalized RTE cell lines produce three mRNA transcripts [2.5, 1.9, 1.4 kilobases (kb)] which hybridize to a murine transforming growth factor beta1 (TGF-beta1) complementary DNA probe. In this report, we show that the 1.9- and 1.4-kb transcripts are not detectable by Northern analysis of resting adult trachea but are induced in regenerating tracheal grafts and tumors formed from transformed RTE cells. Northern analysis of the TGF-beta1 transcripts with subclones of the murine complementary DNA demonstrate that the 1.4-kb transcript lacks much of the 5' untranslated region (UTR). RNase protection analysis was used to map the transcriptional start site of the 1.4-kb transcript to within 30-40 base pairs of the first ATG codon. No differences in the coding or 3' UTR were detected between the 1.4-kb and the 2.5-kb transcripts. Although RTE cells produce a 1.9-kb TGF-beta1 mRNA, we were unable to detect a previously reported unique 3' UTR, which we found to be almost identical to a rat mitochondrial ATPase sequence. Because the 1.4-kb transcript is missing most of the long GC-rich 5' UTR, it may be translated at a different rate than the 2.5- and 1.9-kb transcripts, or it may code for an intracellular form of TGF-beta1. The 1.4-kb transcript has been observed under several conditions of injury or stress and, therefore, may be an important component of the TGF-beta1 response to these conditions. RP OSTROWSKI, LE (reprint author), NIEHS,EPITHELIAL CARCINOGENESIS GRP,PULM PATHOL LAB,MAIL DROP D2-01,RES TRIANGLE PK,NC 27709, USA. NR 40 TC 7 Z9 7 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 DEC PY 1993 VL 4 IS 12 BP 985 EP 991 PG 7 WC Cell Biology SC Cell Biology GA ML312 UT WOS:A1993ML31200004 PM 8117625 ER PT J AU OWEN, RD HOSOI, J MONTGOMERY, JC WISEMAN, R BARRETT, JC AF OWEN, RD HOSOI, J MONTGOMERY, JC WISEMAN, R BARRETT, JC TI COORDINATE REGULATION OF COLLAGEN-II(ALPHA(1)) AND H19 EXPRESSION IN IMMORTALIZED HAMSTER-CELLS SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID TUMOR-SUPPRESSOR GENE; MESSENGER-RNA; EMBRYO CELLS; RAS ONCOGENE; WILMS-TUMOR; COLLAGEN; DIFFERENTIATION; FIBROBLASTS; IDENTIFICATION; CANCER AB Loss of tumor suppressor gene function is essential in the multistep progression of cells to neoplasia. Immortalized cells were established by carcinogen treatment of Syrian hamster embryo cells. At early passages, these nontumorigenic cells retained the ability to suppress tumorigenicity in cell hybrids with malignant cells. Upon passage and subcloning of these suppressor-positive (supB+) cells, variant clones that had lost tumor suppressor activity were isolated. These suppressor-negative (supB-) clones remained nontumorigenic. The mRNAs encoding collagen II(alpha1a), a chondrocyte differentiation marker, and H19, a developmentally controlled gene, were more abundant in supB+ cells than in supB- cells. Nuclear run-on analysis indicated that the transcription of these genes is differentially regulated. Transient transfection experiments revealed that a cis-acting element in the rat collagen II 5' flanking sequences directs differentially regulated transcription. Gel retention analysis demonstrated the presence of a nuclear DNA-binding factor(s) that specifically recognizes a DNA sequence common to both the rat collagen II sequences and the mouse H19 enhancer. In one set of clones, transcriptional regulation could account for differential collagen II and H19 expression in supB+ and supB- cells. In another set of clones, posttranscriptional controls are responsible for the decreased expression of these genes in supB- cells. The emergence of two independent mechanisms that cause differential expression of collagen II and H19 related to tumor suppressor loss suggests that coordinate regulation of these genes, or others regulated by common mechanisms, may be important in tumor suppression. RP OWEN, RD (reprint author), NIEHS,MOLEC CARCINOGENESIS LAB,MAIL DROP D2-04,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 58 TC 8 Z9 8 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 DEC PY 1993 VL 4 IS 12 BP 1013 EP 1021 PG 9 WC Cell Biology SC Cell Biology GA ML312 UT WOS:A1993ML31200007 PM 8117615 ER PT J AU AMIN, AR SWENSON, CD XUE, B ISHIDA, Y NAIR, BG PATEL, TB CHUSED, TM THORBECKE, GJ AF AMIN, AR SWENSON, CD XUE, B ISHIDA, Y NAIR, BG PATEL, TB CHUSED, TM THORBECKE, GJ TI REGULATION OF IGD-RECEPTOR EXPRESSION ON MURINE T-CELLS .2. UP-REGULATION OF IGD RECEPTORS IS OBTAINED AFTER ACTIVATION OF VARIOUS INTRACELLULAR SECOND-MESSENGER SYSTEMS - TYROSINE KINASE-ACTIVITY IS REQUIRED FOR THE EFFECT OF IGD SO CELLULAR IMMUNOLOGY LA English DT Article ID PROTEIN-KINASE; MONOCLONAL-ANTIBODY; LYMPHOCYTE-T; HERBIMYCIN-A; COSTIMULATORY SIGNAL; CYCLIC-AMP; B-CELLS; INHIBITOR; PHOSPHORYLATION; STAUROSPORINE C1 NYU MED CTR,DEPT PATHOL,NEW YORK,NY 10016. UNIV TENNESSEE,DEPT PHARMACOL,MEMPHIS,TN 38163. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. FU NIA NIH HHS [AG-10303, AG-04980] NR 60 TC 11 Z9 11 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 DEC PY 1993 VL 152 IS 2 BP 422 EP 439 DI 10.1006/cimm.1993.1302 PG 18 WC Cell Biology; Immunology SC Cell Biology; Immunology GA MP148 UT WOS:A1993MP14800012 PM 8258149 ER PT J AU HUGIN, AW FLEXNER, C MOSS, B AF HUGIN, AW FLEXNER, C MOSS, B TI CLEARANCE OF RECOMBINANT VACCINIA VIRUS EXPRESSING IL-2 - ROLE OF LOCAL HOST IMMUNE-RESPONSES SO CELLULAR IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; GENERALIZED VIRAL-INFECTION; LARGE GRANULAR LYMPHOCYTES; TOXIC T-CELLS; INTERFERON-GAMMA; MACROPHAGE ACTIVATION; IMMUNODEFICIENT MICE; BEIGE MUTATION; GUINEA-PIGS; IFN-GAMMA C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NR 41 TC 13 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD DEC PY 1993 VL 152 IS 2 BP 499 EP 509 DI 10.1006/cimm.1993.1307 PG 11 WC Cell Biology; Immunology SC Cell Biology; Immunology GA MP148 UT WOS:A1993MP14800017 PM 8258152 ER PT J AU SHEPPARD, BC TEMECK, BK TAUBENBERGER, JK PASS, HI AF SHEPPARD, BC TEMECK, BK TAUBENBERGER, JK PASS, HI TI PULMONARY METASTATIC DISEASE IN AMELOBLASTOMA SO CHEST LA English DT Article ID METASTASIZING AMELOBLASTOMA; MALIGNANT AMELOBLASTOMA AB Ameloblastoma is a rare disease of odontogenic origin with indeterminate metastatic potential. The first site of metastatic disease is usually the lung. We report aggressive surgical treatment of a patient with bilateral disease with five subsequent recurrences. A review of the literature suggests that in the absence of effective chemotherapy or radiation, surgery should be considered the treatment of choice for metastatic ameloblastoma confined to the lung. C1 NCI,SURG BRANCH,THORAC ONCOL SECT,BLDG 10,RM 2B42,BETHESDA,MD 20892. NR 31 TC 16 Z9 17 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 DEC PY 1993 VL 104 IS 6 BP 1933 EP 1935 DI 10.1378/chest.104.6.1933 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA ML308 UT WOS:A1993ML30800069 PM 8252997 ER PT J AU LENFANT, C AF LENFANT, C TI MOLECULAR-GENETICS OF HEART, LUNG, AND BLOOD-DISEASES - THE SHAPE OF THINGS TO COME SO CIRCULATION LA English DT Editorial Material RP LENFANT, C (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC PY 1993 VL 88 IS 6 BP 2487 EP 2488 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ML699 UT WOS:A1993ML69900001 PM 8252660 ER PT J AU LENFANT, C AF LENFANT, C TI NHLBI PROGRAMS FOR MINORITY RESEARCHERS - A LIFE IN SCIENCE SO CIRCULATION LA English DT Editorial Material RP LENFANT, C (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC PY 1993 VL 88 IS 6 BP 2488 EP 2488 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ML699 UT WOS:A1993ML69900002 ER PT J AU FLUGELMAN, MY VIRMANI, R CORREA, R YU, ZX FARB, A LEON, MB ELAMI, A FU, YM CASSCELLS, W EPSTEIN, SE AF FLUGELMAN, MY VIRMANI, R CORREA, R YU, ZX FARB, A LEON, MB ELAMI, A FU, YM CASSCELLS, W EPSTEIN, SE TI SMOOTH-MUSCLE CELL ABUNDANCE AND FIBROBLAST GROWTH-FACTORS IN CORONARY LESIONS OF PATIENTS WITH NONFATAL UNSTABLE ANGINA - A CLUE TO THE MECHANISM OF TRANSFORMATION FROM THE STABLE TO THE UNSTABLE CLINICAL STATE SO CIRCULATION LA English DT Article DE SMOOTH MUSCLE CELLS; ANGINA; GROWTH FACTORS ID ANGIOGRAPHIC MORPHOLOGY; ARTERY DISEASE; PECTORIS; PATHOGENESIS; ANGIOPLASTY; RESTENOSIS; DEATH; PROLIFERATION; INFARCTION; MIGRATION AB Background. The mechanisms responsible for the transformation of stable angina to unstable angina, a major cause of morbidity and mortality, are commonly believed to be plaque rupture and thrombosis. We determined whether additional mechanisms are operative by analyzing the histopathology and immuno-histopathology of coronary plaques retrieved by directional atherectomy of patients with unstable angina in whom no intraluminal thrombus was demonstrated by angiography. Methods and Results. The histological findings of atherectomy specimens from 34 patients with unstable angina were compared with those of 24 patients with postangioplasty restenosis, whose lesions are known to be composed of smooth muscle cells (SMCs), and 10 patients with stable angina, whose lesions contain relatively few SMCs. We also studied the expression of acidic and basic fibroblast growth factors (aFGF and bFGF), whose role in the vascular response to injury has been established. Specimens from unstable angina resembled those from postangioplasty restenosis in regard to SMC abundance (scale, 0 to 3; 1.4+/-0.9 versus 1.7+/-0.9; P=NS), and both differed from those of stable angina. Thrombus and/or hemorrhage occurred in only 34% of patients with unstable angina (compared with 6% of restenosis patients and in none of stable angina patients). Active lesions (defined as lesions containing one or more of the following: thrombus, hemorrhage, abundant and disorganized SMCs in the presence of loose connective tissue, or inflammatory infiltrate) were observed in 56% of the unstable angina patients and in 50% of the restenosis patients but in none of the stable angina patients. The expression of aFGF and bFGF was detected in 80% to 1004b of unstable angina (n=11) and restenosis (n=10) specimens but in only 1 of 5 stable angina specimens. Conclusions. Microscopic evidence of thrombosis and plaque rupture occurred in only one third of unstable angina patients, selected because they had no angiographic evidence of intracoronary thrombus. Moreover, their lesions resembled those of restenosis patients in regard to SMC abundance, lesion activity, and the expression of aFGF and bFGF. Our findings therefore suggest that an alternative mechanism to plaque rupture and thrombus formation may be operative in the precipitation of unstable angina; namely, in a subset of patients, SMC proliferation may lead to gradual plaque expansion and thereby to lumenal narrowing and unstable angina. Our data also suggest a role for aFGF and bFGF in this process. C1 NHLBI, CARDIOL BRANCH, BETHESDA, MD 20892 USA. WASHINGTON HOSP CTR, DIV CARDIOL, WASHINGTON, DC USA. ARMED FORCES INST PATHOL, WASHINGTON, DC 20306 USA. UNIV CALIF LOS ANGELES, MED CTR, DIV CARDIOTHORAC SURG, LOS ANGELES, CA USA. NR 36 TC 131 Z9 134 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC PY 1993 VL 88 IS 6 BP 2493 EP 2500 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ML699 UT WOS:A1993ML69900004 PM 7504590 ER PT J AU CASINO, PR KILCOYNE, CM QUYYUMI, AA HOEG, JM PANZA, JA AF CASINO, PR KILCOYNE, CM QUYYUMI, AA HOEG, JM PANZA, JA TI THE ROLE OF NITRIC-OXIDE IN ENDOTHELIUM-DEPENDENT VASODILATION OF HYPERCHOLESTEROLEMIC PATIENTS SO CIRCULATION LA English DT Article DE CHOLESTEROL; ENDOTHELIUM; ACETYLCHOLINE; ARGININE; PLETHYSMOGRAPHY ID FOREARM RESISTANCE VESSELS; VASCULAR SMOOTH-MUSCLE; RELAXING FACTOR; L-ARGININE; RABBIT AORTA; CORONARY MICROCIRCULATION; ESSENTIAL-HYPERTENSION; RELAXATION; ARTERIES; ATHEROSCLEROSIS AB Background. Patients with hypercholesterolemia have a reduced response to endothelium-dependent vasodilators. However, the regulatory function of the endothelium on vascular tone is mediated through the release of several vasoactive substances; therefore, a reduced response to endothelium-dependent agents does not identify which of the factors released by the endothelium is involved in this abnormality. Methods and Results. To investigate the role of nitric oxide in the endothelium-dependent vasodilation in hypercholesterolemia, we studied the effect of N-G-monomethyl-L-arginine (L-NMMA), an inhibitor of endothelial nitric oxide synthesis, on basal vascular tone and on the responses to acetylcholine, an endothelium-dependent vasodilator, and to sodium nitroprusside, a direct smooth muscle dilator. The study included 33 hypercholesterolemic patients (17 men; 51+/8 years; plasma cholesterol, greater than or equal to 240 mg/dL) and 23 normal controls (12 men; 48+/-7 years; plasma cholesterol, <210 mg/dL). Drugs were infused into the brachial artery, and the response of the forearm vasculature was measured by strain-gauge plethysmography. Basal blood flow and vascular resistance were similar in hypercholesterolemic patients and normal controls (3.1+/-1 versus 2.6+/-0.8 mL/min per 100 mL and 32.1+/-13 versus 36.1+/-12 mm Hg/mL(-1).min(-1) 100 mL(-1), respectively). The reduction in basal blood flow and increase in vascular resistance produced by L-NMMA were not significantly different between the two groups. L-NMMA markedly blunted the response to acetylcholine in normals (maximum flow decreased from 16.4+/-8 to 7.0+/-3; P<.005); however, the arginine analogue did not significantly modify the response to acetylcholine in the hypercholesterolemic patients (maximum how, 11.1+/-8 versus 10.0+/-8). L-NMMA did not modify the vasodilator response to sodium nitroprusside in either controls or patients. Conclusions. These findings indicate that hypercholesterolemic patients have a defect in the bioactivity of nitric oxide that may explain their impaired endothelium-dependent vascular relaxation. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NR 43 TC 308 Z9 313 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC PY 1993 VL 88 IS 6 BP 2541 EP 2547 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ML699 UT WOS:A1993ML69900010 PM 8252665 ER PT J AU MURABITO, JM EVANS, JC LARSON, MG LEVY, D AF MURABITO, JM EVANS, JC LARSON, MG LEVY, D TI PROGNOSIS AFTER THE ONSET OF CORONARY HEART-DISEASE - AN INVESTIGATION OF DIFFERENCES IN OUTCOME BETWEEN THE SEXES ACCORDING TO INITIAL CORONARY-DISEASE PRESENTATION SO CIRCULATION LA English DT Article DE ANGINA; MYOCARDIAL INFARCTION; EPIDEMIOLOGY ID ACUTE MYOCARDIAL-INFARCTION; ARTERY DISEASE; RISK-FACTORS; GENDER BIAS; WOMEN; FRAMINGHAM; MEN; MORTALITY; SURVIVAL; PREVALENCE AB Background. Differences exist between men and women in prognosis after the onset of coronary heart disease (CHD). Methods and Results. All Framingham Heart Study subjects with the onset of clinically apparent coronary disease from 1951 through 1986 were studied to compare prognosis in men and women according to CHD presentation. Coronary disease presentations included angina, coronary insufficiency (unstable angina), recognized myocardial infarction, unrecognized myocardial infarction, and coronary death. Less than 1% of subjects were lost to follow-up for overall mortality. Cox modeling was used to examine the sex differences in outcome far each coronary presentation. New nonfatal coronary disease developed in 750 men (mean age, 63 years) and 583 women (mean age, 67 years). After onset of angina, men were at greater risk than women for myocardial infarction (hazards ratio [IIR], 2.20; 95% confidence interval [CI], 1.45 to 3.34) and coronary death (HR, 2.11; 95% CI, 1.32 to 3.36) after adjustment for age and coronary disease risk factors. After a recognized myocardial infarction, there was a trend toward greater risk for overall mortality in women than men after adjustment for age and risk factors (HR, 0.75; 95% CI, 0.53 to 1.08). In contrast, after an unrecognized myocardial infarction, men were at increased risk for death compared with women (HR, 2.01; 95% CI, 1.28 to 3.15). Conclusions. Women fare at least as poorly as men alter recognized myocardial infarction, whereas women have a more favorable outlook than men after the onset of angina or unrecognized myocardial infarction. The favorable outcome in women after angina and unrecognized myocardial infarction is due, in part, to greater misclassification of these coronary events in women than in men. C1 BOSTON UNIV,SCH MED,PREVENT MED & EPIDEMIOL SECT,BOSTON,MA 02118. BOSTON UNIV,SCH MED,GEN MED SECT,BOSTON,MA. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. BETH ISRAEL HOSP,DIV CARDIOL,BOSTON,MA. BETH ISRAEL HOSP,DIV CLIN EPIDEMIOL,BOSTON,MA. RP MURABITO, JM (reprint author), FRAMINGHAM HEART DIS EPIDEMIOL STUDY,5 THURBER ST,FRAMINGHAM,MA 01701, USA. FU NHLBI NIH HHS [N01-HC-38038] NR 37 TC 140 Z9 147 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC PY 1993 VL 88 IS 6 BP 2548 EP 2555 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ML699 UT WOS:A1993ML69900011 PM 8252666 ER PT J AU YANO, K GROVE, JS REED, DM CHUN, HM AF YANO, K GROVE, JS REED, DM CHUN, HM TI DETERMINANTS OF THE PROGNOSIS AFTER A FIRST MYOCARDIAL-INFARCTION IN A MIGRANT JAPANESE POPULATION - THE HONOLULU-HEART-PROGRAM SO CIRCULATION LA English DT Article DE MYOCARDIAL INFARCTION; PROGNOSIS; HEART DISEASE; RISK FACTORS ID NON-Q-WAVE; LONG-TERM PROGNOSIS; COMMUNITY-WIDE PERSPECTIVE; NATURAL-HISTORY; BLOOD-PRESSURE; RISK-FACTORS; DISEASE; SURVIVAL; FRAMINGHAM; MEN AB Background. Although numerous studies have been published on the prognostic assessment of myocardial infarction, little is known about determinants of the prognosis after a first myocardial infarction, especially regarding the role of standard risk factors for coronary heart disease (CHD) measured before the development of myocardial infarction. Methods and Results. In a prospective study of CHD among men of Japanese ancestry living in Hawaii, 457 patients with a first myocardial infarction (age range, 46 to 84 years) were identified during 20 years of follow-up. The relations of clinical variables and CHD risk factors to mortality in early (<30 days) and two stages of late (30 days to 5 years and 5 to 10 years) periods after myocardial infarction in these patients were investigated. In multivariate analyses using logistic regression models (for early mortality) and Cox regression models (for late mortality), age at myocardial infarction and severe complications (Killip classes 3 and 4) were independent predictors of both early and late mortality (up to 5 years after myocardial infarction). In addition, ventricular arrhythmias predicted only early mortality, whereas anterior myocardial infarction, radiological evidence of cardiomegaly and/or pulmonary congestion, and intraventricular block predicted only late mortality (up to 5 years after myocardial infarction). Only age was an independent predictor of all-cause mortality more than 5 years after myocardial infarction. After adjusting for age at myocardial infarction and these clinical variables, preinfarction-measured risk factors such as I-hour postload serum glucose (positively) and 1-second forced expiratory volume (inversely) were significantly associated with late mortality up to 5 years, whereas systolic blood pressure was the only independent predictor of late mortality after 5 years. Conclusions. This study has confirmed the importance of age at myocardial infarction and clinical indicators of complications such as Killip class 3 or 4, radiological evidence of pulmonary congestion, and ventricular arrhythmias or intraventricular block as the prognostic determinants of myocardial infarction. In addition, some of the preinfarction-measured standard risk factors for CHD were found to predict long-term prognosis independent of age and clinical factors. C1 UNIV HAWAII,SCH PUBL HLTH,DEPT PUBL HLTH,BIOSTAT PROGRAM,HONOLULU,HI 96822. NHLBI,HONULULU HEART PROGRAM,HONOLULU,HI. RP YANO, K (reprint author), KUAKINI MED CTR,HONOLULU HEART PROGRAM,347 N KUAKINI ST,HONOLULU,HI 96817, USA. FU NHLBI NIH HHS [N01-HC-02901] NR 64 TC 10 Z9 10 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC PY 1993 VL 88 IS 6 BP 2582 EP 2595 PG 14 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ML699 UT WOS:A1993ML69900015 PM 8252669 ER PT J AU DEMIROVIC, J NABULSI, A FOLSOM, AR CARPENTER, MA SZKLO, M SORLIE, PD BARNES, RW AF DEMIROVIC, J NABULSI, A FOLSOM, AR CARPENTER, MA SZKLO, M SORLIE, PD BARNES, RW TI ALCOHOL-CONSUMPTION AND ULTRASONOGRAPHICALLY ASSESSED CAROTID-ARTERY WALL THICKNESS AND DISTENSIBILITY SO CIRCULATION LA English DT Article DE ATHEROSCLEROSIS; ALCOHOL; ULTRASONOGRAPHY ID CORONARY HEART-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; IMPROVED LIPOLYTIC EFFICIENCY; B-MODE ULTRASOUND; RISK-FACTORS; ENZYMATIC DETERMINATION; ATHEROSCLEROSIS; STROKE; MORTALITY; PLASMA AB Background. Although much has been written in recent years about the relation between alcohol and atherosclerotic disease, controversy exists as to whether and how alcohol exerts an effect on atherosclerosis in different sites. Methods and Results. We tested the hypothesis that alcohol consumption is associated inversely with carotid atherosclerosis in a population sample of 45- to 64-year-old men and women who participated in the Atherosclerosis Risk in Communities (ARIC) Study and were free of cardiovascular disease at a baseline examination in 1987 to 1989. B-mode ultrasonography was used to determine carotid artery intimal-medial wall thickness and distensibility as indices of the degree of atherosclerosis. The level of alcohol consumption in the ARIC sample was generally low. Age-adjusted mean values of alcohol consumed (grams per week) were 72.0 for white and 74.3 for nonwhite men and 24.8 for white and 11.2 for nonwhite women. After adjustments for age, artery depth, education, body mass index, sport index, cigarette-years of smoking, low-density lipoprotein cholesterol, and diabetes mellitus, there was no significant cross-sectional association of reported current alcohol intake with either carotid artery wall thickness (among white and nonwhite men and nonwhite women) or distensibility (in any of the four sex-race groups). Among white women, the adjusted mean value of carotid artery wall thickness tended to be higher in light to moderate drinkers than in never or rare drinkers, but the difference across drinking status categories was of borderline statistical significance (P=.04) and may be of little biological importance. Conclusions. The ARIC Study found no material cross-sectional association between current alcohol intake and carotid atherosclerosis but provides an opportunity in the future to study atherosclerosis progression and incident events in relation to alcohol consumption in a large population sample of men and women. C1 UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,MINNEAPOLIS,MN 55455. UNIV MIAMI,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,MIAMI,FL. UNIV N CAROLINA,SCH PUBL HLTH,COLLABORAT STUDIES COORDINATING CTR,CHAPEL HILL,NC. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. ULTRASOUND READING CTR,WINSTON SALEM,NC. FU NHLBI NIH HHS [N01-HC-55018, N01-HC-55016, N01-HC-55015] NR 53 TC 54 Z9 54 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC PY 1993 VL 88 IS 6 BP 2787 EP 2793 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ML699 UT WOS:A1993ML69900038 PM 8252692 ER PT J AU GUZMAN, PJ LEMARCHAND, P CRYSTAL, RG EPSTEIN, SE FINKEL, T AF GUZMAN, PJ LEMARCHAND, P CRYSTAL, RG EPSTEIN, SE FINKEL, T TI EFFICIENT AND SELECTIVE ADENOVIRUS-MEDIATED GENE-TRANSFER INTO VASCULAR NEOINTIMA SO CIRCULATION LA English DT Article DE ADENOVIRUS; NEOINTIMA ID LUMINAL CORONARY ANGIOPLASTY; FIBROBLAST GROWTH-FACTOR; SMOOTH-MUSCLE CELLS; ENDOTHELIAL-CELLS; BALLOON CATHETER; ARTERIAL INJURY; FOLLOW-UP; RESTENOSIS; INVIVO; PROLIFERATION AB Background. Previous attempts to target arterial smooth muscle cells (SMCs) for gene delivery using liposomal or retroviral methods were limited by low transfection efficiency. We therefore evaluated the efficiency of adenovirus-mediated gene delivery in cultured vascular SMCs and in an in vivo model of balloon injury-induced SMC cell proliferation, Methods and Results. We used a recombinant adenovirus, Ad.RSV beta gal, which contained the beta-galactosidase (beta-gal) histochemical marker gene. For in vitro studies, rat aortic SMCs were incubated in media containing Ad.RSV beta gal for 5 to 120 minutes. The proportion of SMCs expressing the beta-gal gene product increased from 25% (5-minute exposure) to 80% (120-minute exposure). For in vivo studies, uninjured and injured rat carotid segments were incubated with 0.5 to 1.0x10(9) pfu Ad.RSV beta gal for 45 minutes. Uninjured arteries showed adenovirus-mediated gene transfer limited to the endothelium. Injured arteries were exposed to adenovirus 0, 3, 7, or 12 days after injury. In these segments, beta-gal expression was minimal with infection at 0 or 3 days after injury but marked when infection was delayed until 7 or 12 days after injury. Neointimal cells constituted the dominant target of adenovirus gene transfer, with efficiency of gene transfer ranging from 10% to >75%. Medial SMCs, whether covered or uncovered by neointimal cells, were minimally infected, Infection with a control adenovirus vector showed no beta-gal staining. Conclusions. Recombinant adenovirus selectively targets neointimal cells with high-efficiency gene transfer. This suggests that adenovirus vectors should be useful in targeting cells for the delivery of genes whose products may be relevant to the treatment of restenosis. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NHLBI,PULM BRANCH,BETHESDA,MD 20892. RI lemarchand, patricia/C-3247-2011 NR 48 TC 3 Z9 3 U1 0 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC PY 1993 VL 88 IS 6 BP 2838 EP 2848 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ML699 UT WOS:A1993ML69900043 ER PT J AU SOLARO, RJ GAMBASSI, G WARSHAW, DM KELLER, MR SPURGEON, HA BEIER, N LAKATTA, EG AF SOLARO, RJ GAMBASSI, G WARSHAW, DM KELLER, MR SPURGEON, HA BEIER, N LAKATTA, EG TI STEREOSELECTIVE ACTIONS OF THIADIAZINONES ON CANINE CARDIAC MYOCYTES AND MYOFILAMENTS SO CIRCULATION RESEARCH LA English DT Article DE CA2+; CONTRACTION; THIADIAZINONE DERIVATIVES; MYOFILAMENT CA2+ SENSITIVITY; INOTROPIC AGENTS ID INORGANIC-PHOSPHATE; STRIATED-MUSCLE; TROPONIN-C; ATPASE ACTIVITY; ACIDIC PH; CALCIUM; MYOFIBRILS; BINDING; MYOCARDIUM; ACTIVATION AB Thiadiazinones are cardiotonic agents that have potent, direct, and stereoselective actions on the myofilament response to Ca2+ in intact myocardium. Their mechanism of action is unknown. We studied the effects of racemic thiadiazinone, EMD 53998 (5-[1-(3,4-dimethoxybenzoyl)-1,2,3,4-tetrahydro-6-quinolyl]-6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-one), and its enantiomers on Ca2+ signaling in myocytes, myofilaments, and myofilament proteins. Intact canine ventricular myocytes responded to the positive enantiomer, EMD 57033, with an increase in the extent of shortening during twitch contractions without increasing the peak amplitude of the Ca2+ transient. The negative enantiomer, EMD 57439, also increased the extent of shortening, but in this case there was a concentration-dependent increase in the peak amplitude of the Ca2+ transient. This is predicted from in vitro data showing that this enantiomer is a relatively potent inhibitor of phosphodiesterase activity. There was no effect of EMD 57439 on the relation between pCa and actomyosin Mg-ATPase activity of canine heart myofibrils. In contrast, EMD 57033 shifted the pCa-Mg-ATPase activity relation to the left. There was no effect of either enantiomer on Ca2+ binding to myofilament troponin C. Moreover EMD 57033, but not EMD 57439, stimulated actomyosin ATPase activity of myofilament preparations in which either troponin or troponin-tropomyosin had been extracted. EMD 57033 had no effect on Mg-ATPase activity of pure ventricular myosin. EMD 57033 also stimulated the velocity of actin filament sliding on myosin heads adhered to nitrocellulose-coated glass coverslips. We propose that the action of EMD 57033 is at the actin-myosin interface on a ''receptor'' that may be on actin or the crossbridge. Drug binding to this domain appears to reverse the inhibition of actin-myosin interactions by troponin-tropomyosin and also to promote transition of crossbridges from weak to strong force-generating states. C1 UNIV VERMONT,DEPT PHYSIOL & BIOPHYS,BURLINGTON,VT. E MERCK AG,DEPT CARDIOVASC BIOCHEM,W-6100 DARMSTADT,GERMANY. NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. RP SOLARO, RJ (reprint author), UNIV ILLINOIS,COLL MED,DEPT PHYSIOL & BIOPHYS,M-C 901,901 S WOLCOTT AVE,CHICAGO,IL 60612, USA. FU NHLBI NIH HHS [R01 HL-22231, R01 HL-45161] NR 35 TC 163 Z9 163 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD DEC PY 1993 VL 73 IS 6 BP 981 EP 990 PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA MH644 UT WOS:A1993MH64400001 PM 8222092 ER PT J AU GUZMAN, RJ LEMARCHAND, P CRYSTAL, RG EPSTEIN, SE FINKEL, T AF GUZMAN, RJ LEMARCHAND, P CRYSTAL, RG EPSTEIN, SE FINKEL, T TI EFFICIENT GENE-TRANSFER INTO MYOCARDIUM BY DIRECT-INJECTION OF ADENOVIRUS VECTORS SO CIRCULATION RESEARCH LA English DT Note DE GENE THERAPY; ADENOVIRUS ID RAT-HEART INVIVO; EXPRESSION; EPITHELIUM; DNA AB Previous studies have established that gene transfer into myocardial cells in vivo is detectable after direct injection of plasmid DNA. Recently, adenovirus vectors have been shown to provide an efficient method for gene transfer into a wide range of tissues. Therefore, this study sought to assess the efficiency and stability of adenovirus-mediated gene transfer into myocardium and to compare this method with that using plasmid-based gene transfer techniques. Adult rats underwent myocardial injection via a subdiaphragmatic approach. Gene transfer efficiency was compared using direct injection of an adenovirus vector encoding for the marker gene beta-galactosidase (beta-gal), a control adenovirus vector encoding for the cystic fibrosis transmembrane conductance regulator gene, a plasmid encoding for beta-gal, or a control plasmid. Hearts infected with an adenovirus vector containing the beta-gal gene showed significantly increased beta-gal enzymatic activity compared with hearts injected with beta-gal plasmid. Histological examination revealed that cardiac myocytes were the target of adenovirus-mediated gene transfer. A time course of gene expression showed that beta-gal enzymatic activity peaked during the first week following injection. Adenovirus vectors provide an efficient but transient method for in vivo gene expression in myocardium. C1 NHLBI,CARDIOL BRANCH,BLDG 10,RM 7B15,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NHLBI,PULM BRANCH,BETHESDA,MD 20892. RI lemarchand, patricia/C-3247-2011 NR 22 TC 204 Z9 209 U1 1 U2 5 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD DEC PY 1993 VL 73 IS 6 BP 1202 EP 1207 PG 6 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA MH644 UT WOS:A1993MH64400022 PM 8222091 ER PT J AU FRIEDMAN, TC CHROUSOS, GP AF FRIEDMAN, TC CHROUSOS, GP TI TRANSSPHENOIDAL RESECTION IN CUSHINGS-DISEASE - DEFINITION OF SUCCESS SO CLINICAL ENDOCRINOLOGY LA English DT Letter C1 NICHHD,LDN,BETHESDA,MD 20892. RP FRIEDMAN, TC (reprint author), NICHHD,DEB,BETHESDA,MD 20892, USA. NR 3 TC 9 Z9 9 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD DEC PY 1993 VL 39 IS 6 BP 701 EP 701 DI 10.1111/j.1365-2265.1993.tb02431.x PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MM224 UT WOS:A1993MM22400013 PM 8287590 ER PT J AU DEUTSCH, SI ROSSE, RB KENDRICK, KA FAYMCCARTHY, M COLLINS, JP WYATT, RJ AF DEUTSCH, SI ROSSE, RB KENDRICK, KA FAYMCCARTHY, M COLLINS, JP WYATT, RJ TI FAMOTIDINE ADJUNCTIVE PHARMACOTHERAPY FOR SCHIZOPHRENIA - PRELIMINARY DATA SO CLINICAL NEUROPHARMACOLOGY LA English DT Review DE FAMOTIDINE; HISTAMINE; H2 RECEPTOR; H2 ANTAGONIST; SCHIZOPHRENIA; SCHIZOAFFECTIVE DISORDER ID NEGATIVE SYMPTOMS; DEFINITION; RECEPTORS AB The usefulness of the histamine-2 (H2) antagonist famotidine as an adjunct to conventional antipsychotic treatments of idiopathic psychotic disorders (i.e., schizophrenia and schizoaffective disorder) was investigated in an open-label study. After stabilization for at least 1 week with their conventional antipsychotic medication regimen, 10 patients completed a 3-week study period in which famotidine (20 mg twice a day) was added as an adjunctive medication. The 10 patients were all somewhat treatment refractory and had spent a mean of 230 days of the previous 2 years in the hospital. Total Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression scores were significantly lower during the 3 weeks with famotidine compared with the week before and after its administration. Nevertheless, review of the scores revealed that the magnitude of the changes were small. Negative symptoms as measured by the Schedule for the Assessment of Negative Symptoms (SANS) were not significantly different during famotidine treatment, although there was the tendency for total SANS scores to be lower during famotidine treatment. When BPRS items were divided into specific versus nonspecific symptom subscales, only the specific-item subscales had significantly improved during famotidine treatment. The results of this study suggest that famotidine might prove a useful adjunctive agent in certain patients with schizophrenia. Future studies using a double-blind placebo-controlled design and higher doses are needed. Additionally, other H2 receptor antagonists with better penetration across the blood-brain barrier should be pursued. C1 GEORGETOWN UNIV,SCH MED,DEPT PSYCHIAT,WASHINGTON,DC. NIMH,NEUROSCI CTR ST ELIZABETHS,NEUROPSYCHIAT BRANCH,WASHINGTON,DC. RP DEUTSCH, SI (reprint author), DEPT VET AFFAIRS MED CTR,PSYCHIAT SERV,ROOM 3A154-116A,50 IRVING ST,NW,WASHINGTON,DC 20422, USA. NR 14 TC 26 Z9 26 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0362-5664 J9 CLIN NEUROPHARMACOL JI Clin. Neuropharmacol. PD DEC PY 1993 VL 16 IS 6 BP 518 EP 524 PG 7 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA MH530 UT WOS:A1993MH53000005 PM 9377587 ER PT J AU HITRI, A WYATT, RJ AF HITRI, A WYATT, RJ TI REGIONAL DIFFERENCES IN RAT-BRAIN DOPAMINE TRANSPORTER BINDING - FUNCTION OF TIME AFTER CHRONIC COCAINE SO CLINICAL NEUROPHARMACOLOGY LA English DT Review DE COCAINE; DOPAMINE TRANSPORTER; [H-3] GBR 12935; FRONTAL CORTEX; COCAINE WITHDRAWAL ID POSITRON EMISSION TOMOGRAPHY; UPTAKE SITES; GBR-12935 BINDING; STRIATAL DOPAMINE; NUCLEUS-ACCUMBENS; EXTRANEURONAL UPTAKE; PARKINSONS-DISEASE; NONHUMAN-PRIMATES; CAUDATE-NUCLEUS; FRONTAL-CORTEX AB Chronic administration of cocaine to rats has been shown to produce a persistent decrease in dopamine (DA) and its metabolites in the brain and periphery. To further explore the alterations in the DA system following repeated administration of cocaine, we studied the regional differences in DA transporter binding as a function of time after the last injection of cocaine. Two groups of rats were treated with cocaine (10 mg/kg twice a day) or saline for 7 days. Rats were sacrificed 1, 2, 3, 6, and 12 weeks after the last injection. The corpus striatum and the frontal cortex were dissected and assayed with [H-3]GBR 12935 for DA transporter binding. Time-related differences were observed in the frontal cortex but not in the striatum of the saline-treated control rats. Cocaine treatment prevented the time-dependent increase in B-max over the course of 6 weeks, but not over the course of 12 weeks following withdrawal. Although there was no difference between the cocaine- and saline-treated group in the striatum at any of the time points, cocaine in the frontal cortex produced a 33% reduction in B-max during weeks 2 and 3 and a 57% reduction in B-max at week 6 of withdrawal; the reduction persisted for greater than or equal to 12 weeks. The K-D was not affected by cocaine or time in either brain region. These findings may be functionally related to cocaine craving because the DA transporter has been identified as the neuronal structure and the medial prefrontal cortex as the anatomical site mediating cocaine reinforcement. C1 NIMH,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. NR 56 TC 20 Z9 20 U1 4 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0362-5664 J9 CLIN NEUROPHARMACOL JI Clin. Neuropharmacol. PD DEC PY 1993 VL 16 IS 6 BP 525 EP 539 DI 10.1097/00002826-199312000-00006 PG 15 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA MH530 UT WOS:A1993MH53000006 PM 9377588 ER PT J AU SULLIVAN, JT JASINSKI, DR JOHNSON, RE AF SULLIVAN, JT JASINSKI, DR JOHNSON, RE TI SINGLE-DOSE PHARMACODYNAMICS OF DIAZEPAM AND PENTOBARBITAL IN SUBSTANCE-ABUSERS SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID RELATIVE ABUSE; DRUG-THERAPY; BENZODIAZEPINES; WITHDRAWAL; HUMANS; PREFERENCE; LIABILITY; MORPHINE; PLACEBO AB The likelihood that a given drug will be misused is related to its ability to alter mood, feeling, thinking, and perception in a manner that is liked by substance abusers. The subjective and behavioral effects of diazepam (10, 20, and 40 mg), pentobarbital (120 and 240 mg as a positive control), and placebo (negative control), were,evaluated in 12 subjects with histories of substance abuse by use of a double-blind, Latin square crossover study design. Drug administration was separated by a minimum of 3 days. Pharmacodynamic measures included subjective (euphoria, subject liking, sedation, and symptoms) and behavioral (signs and observed liking) responses. The time course and profile of subjective and behavioral responses were similar for diazepam and pentobarbital. Valid relative potency estimates for the pharmacodynamic measures indicated that diazepam is approximately 10 times as potent as pentobarbital. The study indicates that the reinforcing effects of diazepam are similar to pentobarbital in substance abusers. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT,BALTIMORE,MD 21205. NIDA,ADDICT RES CTR,BALTIMORE,MD. FU NIDA NIH HHS [DA-06120] NR 30 TC 3 Z9 3 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD DEC PY 1993 VL 54 IS 6 BP 645 EP 653 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MU532 UT WOS:A1993MU53200008 PM 8275619 ER PT J AU COLEMAN, MB ADAMS, JG SMITH, CM STEINBERG, MH AF COLEMAN, MB ADAMS, JG SMITH, CM STEINBERG, MH TI MODULATION OF HB KOLN DISEASE BY AN ADDITIONAL MUTATION - HB MEDICINE LAKE SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 VET ADM MED CTR,JACKSON,MS 39216. NIH,BETHESDA,MD 20892. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. 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 DEC PY 1993 VL 41 IS 4 BP A761 EP A761 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA MN948 UT WOS:A1993MN94800249 ER PT J AU MALLOY, MH GRAUBARD, B AF MALLOY, MH GRAUBARD, B TI PREDICTORS OF REHOSPITALIZATION AMONG VERY-LOW-BIRTH-WEIGHT INFANTS (VLBW) SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 UNIV TEXAS,MED BRANCH,GALVESTON,TX 77550. NCI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 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 DEC PY 1993 VL 41 IS 4 BP A791 EP A791 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA MN948 UT WOS:A1993MN94800409 ER PT J AU MORRELL, CH PEARSON, JD BRANT, LJ AF MORRELL, CH PEARSON, JD BRANT, LJ TI MODELING PATTERNS OF CHANGE WITH AGE AS A RISK FACTOR OF DISEASE AND MORTALITY SO COLLEGIUM ANTROPOLOGICUM LA English DT Article ID LONGITUDINAL DATA AB Past research has shown that human development is characterized by varying patterns of change in individual characteristics as a person grows older. Longitudinal studies have emerged as the only way to study these different patterns of change or aging. This paper discusses analytical methods for studying longitudinal data and statistical models for investigating age-related patterns of change as a risk factor for morbidity or mortality. First, methods and models for analyzing longitudinal data are presented with particular attention paid to the assumptions of the models. The three approaches discussed are the >>naively-pooled<< approach, the two-stage approach, and an approach using the linear mixed-effects model for repeated measures data. The model for this final approach most adequately meets the requirements of longitudinal data, allowing for the natural heterogeneity among subjects and providing for a correlation structure for repeated observations across time. Second, three other approaches using the results from the mixed-effects model are discussed for assessing the risk of age-related changes in relation to a subsequent outcome of morbidity or mortality. The first method simply includes variables in the mixed-effects model to account for the age-related differences, the second relates the values of the random effects representing the individual variability to the outcome, and the final approach uses predicted values calculated from the mixed-effects model as covariates in a time-dependent proportional hazards model to investigate the relationship of change with the outcome of interest. RP MORRELL, CH (reprint author), NIA, GERONTOL RES CTR, 4940 EASTERN AVE, BALTIMORE, MD 21224 USA. NR 16 TC 1 Z9 1 U1 0 U2 0 PU COLLEGIUM ANTROPOLOGICUM PI ZAGREB PA INST ANTHROPOLOGICAL RESEARCH, GAJEVA 32, PO BOX 290, HR-10000 ZAGREB, CROATIA SN 0350-6134 J9 COLLEGIUM ANTROPOL JI Coll. Anthropol. PD DEC PY 1993 VL 17 IS 2 BP 327 EP 338 PG 12 WC Anthropology SC Anthropology GA MP682 UT WOS:A1993MP68200017 ER PT J AU PAO, ML GREFSHEIM, SF BARCLAY, ML WOOLLISCROFT, JO MCQUILLAN, M SHIPMAN, BL AF PAO, ML GREFSHEIM, SF BARCLAY, ML WOOLLISCROFT, JO MCQUILLAN, M SHIPMAN, BL TI FACTORS AFFECTING STUDENTS USE OF MEDLINE SO COMPUTERS AND BIOMEDICAL RESEARCH LA English DT Article ID CLINICAL END-USER; INFORMATION MANAGEMENT; SEARCHING BEHAVIOR; PHYSICIANS; NEEDS; DISCRIMINATE; EXPERIENCE; QUESTIONS; SYSTEMS; CARE C1 UNIV MICHIGAN,TAUBMAN MED LIB,ANN ARBOR,MI 48109. UNIV MICHIGAN,SCH MED,ANN ARBOR,MI 48109. NIH LIB,BETHESDA,MD 20892. RP PAO, ML (reprint author), UNIV MICHIGAN,SCH INFORMAT & LIB STUDIES,ANN ARBOR,MI 48109, USA. NR 29 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 0010-4809 J9 COMPUT BIOMED RES JI Comput. Biomed. Res. PD DEC PY 1993 VL 26 IS 6 BP 541 EP 555 DI 10.1006/cbmr.1993.1038 PG 15 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA MM975 UT WOS:A1993MM97500004 PM 8112055 ER PT J AU ROSENDORF, LL DAFNI, U AMATO, DA LUNGHOFER, B BARTLETT, JG LEEDOM, JM WARA, DW ARMSTRONG, JA GODFREY, E SUKKESTAD, E COUNTS, GW AF ROSENDORF, LL DAFNI, U AMATO, DA LUNGHOFER, B BARTLETT, JG LEEDOM, JM WARA, DW ARMSTRONG, JA GODFREY, E SUKKESTAD, E COUNTS, GW TI PERFORMANCE EVALUATION IN MULTICENTER CLINICAL-TRIALS - DEVELOPMENT OF A MODEL BY THE AIDS CLINICAL-TRIALS GROUP SO CONTROLLED CLINICAL TRIALS LA English DT Article DE PERFORMANCE MONITORING; PERFORMANCE EVALUATION; CLINICAL TRIAL; MODELING; AIDS; ACTG; PERFORMANCE SCORE ID ONCOLOGY-GROUP; PARTICIPATION; QUALITY AB The AIDS Clinical Trials Group (ACTG), supported by the National Institute of Allergy and Infectious Diseases (NIAID), is the largest federally funded program of AIDS clinical trials. It is a collaboration involving 59 institutions and affiliated clinical centers, known as AIDS Clinical Trials Units (ACTUs), NIAID staff, and a Statistical and Data Analysis Center (SDAC). An institutional evaluation tool was developed to evaluate ACTU performance, distinguish between clinical centers with superior performance and those not meeting standards, and assist NIAID in allocating funding based on performance. The evaluation tool was designed to reflect the many distinguishing features of ACTG study protocols and clinical trial centers in order to measure performance objectively. The evaluation focused on assessing the financial resources expended by the ACTU in recruiting, treating, and following study patients during the evaluation period; the number of women and minorities enrolled; and the ACTU's scientific contributions to the ACTG. To help quantify the ACTU's performance in enrolling study subjects, a formula was derived to assess the total effort required to screen, enroll, treat, and assess subjects participating in ACTG studies. A weighting system was developed for each study protocol to account for the variations in effort and resources required by the different protocols. Future directions in the ACTG evaluation process include strategies to evaluate performance in relation to quality of data and to determine ways in which the evaluation process can be used to enhance the achievement of programmatic goals. C1 HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. FRONTIER SCI & TECH RES FDN,AMHERST,NY. JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD 21205. UNIV SO CALIF,LOS ANGELES,CA. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. UNIV PITTSBURGH,PITTSBURGH,PA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP ROSENDORF, LL (reprint author), NIAID,POLICY ANAL & LEGISLAT BRANCH,BLDG 31,ROOM 7A51,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [AI-27662, AI-27673, AI-95030] NR 10 TC 6 Z9 6 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD DEC PY 1993 VL 14 IS 6 BP 523 EP 537 DI 10.1016/0197-2456(93)90032-9 PG 15 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA MQ653 UT WOS:A1993MQ65300006 PM 8119067 ER PT J AU KUSEK, JW COYNE, T DEVELASCO, A DRABIK, MJ FINLAY, RA GASSMAN, JJ KIEFER, S POWERS, SN STEINMAN, TI AF KUSEK, JW COYNE, T DEVELASCO, A DRABIK, MJ FINLAY, RA GASSMAN, JJ KIEFER, S POWERS, SN STEINMAN, TI TI RECRUITMENT EXPERIENCE IN THE FULL-SCALE PHASE OF THE MODIFICATION OF DIET IN RENAL-DISEASE STUDY SO CONTROLLED CLINICAL TRIALS LA English DT Article DE RECRUITMENT; RENAL DISEASE; PHYSICIAN REFERRAL; RANDOMIZED CLINICAL TRIAL ID PROTEIN RESTRICTION; CLINICAL-TRIALS; PROGRESSION; INSUFFICIENCY AB The Modification of Diet in Renal Disease (MDRD) Study is a randomized, multicenter clinical trial testing the effects of three different levels of dietary protein and phosphorus intake and two levels of blood pressure control on the rate of loss of kidney function in persons with various chronic kidney diseases. During a 27-month recruitment period, 2507 persons who had objective evidence of impaired kidney function were screened at 15 centers. Eight hundred and forty men and women aged 18-70 with a glomerular filtration rate between 13 and 55 ml/min/1.73 m(2) were randomized. Medical record review was the primary means of identifying study participants at the beginning of recruitment. Later, use of mass media was instrumental in alerting both the public and the medical community of the need for MDRD Study participants. Overall, the most important sources of randomized participants were referral by personal physician (45.4%) and relative/friend (5.6%), and self-referral after hearing about the trial from newspapers (23.9%) and television (5.2%). Review of medical records from defined patient populations was the source of 22.3% of the randomized study participants. A total of 9.4% of the randomized participants called a toll-free (800) telephone number before contacting the centers. C1 UNIV PITTSBURGH,PITTSBURGH,PA. UNIV MIAMI,CORAL GABLES,FL 33124. NIH,BETHESDA,MD 20892. UNIV FLORIDA,GAINESVILLE,FL. UNIV SO CALIF,LOS ANGELES,CA. VANDERBILT UNIV,NASHVILLE,TN. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. RP KUSEK, JW (reprint author), CLEVELAND CLIN FDN,MDRD DATA COORDINATING CTR,DEPT BIOSTAT & EPEDEMIOL,9500 EUCLID AVE,CLEVELAND,OH 44195, USA. FU NIDDK NIH HHS [U01 DK34513, U01 DK34495, U01 DK37072] NR 18 TC 37 Z9 37 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD DEC PY 1993 VL 14 IS 6 BP 538 EP 557 DI 10.1016/0197-2456(93)90033-A PG 20 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA MQ653 UT WOS:A1993MQ65300007 PM 8119068 ER PT J AU MAUVIEL, A CHEN, YQ DONG, W EVANS, CH UITTO, J AF MAUVIEL, A CHEN, YQ DONG, W EVANS, CH UITTO, J TI TRANSCRIPTIONAL INTERACTIONS OF TRANSFORMING GROWTH-FACTOR-BETA WITH PRO-INFLAMMATORY CYTOKINES SO CURRENT BIOLOGY LA English DT Article ID TUMOR NECROSIS FACTOR; HUMAN DERMAL FIBROBLASTS; CELL-DERIVED CYTOKINE; GENE-EXPRESSION; C-JUN; MESSENGER-RNA; PROMOTER ACTIVITY; INTERLEUKIN-8 GENE; MAMMALIAN-CELLS; FOS PROTEINS AB Background: Inflammation and tissue injury are characterized by a massive infiltration of mononuclear cells. These pro-inflammatory cells, which are the precursors of an inflammatory response by the immune system, secrete a variety of cytokines and growth factors that alter the biosynthetic repertoire of the resident connective tissue cells. Specifically, expression of connective tissue matrix metalloproteinases, such as stromelysin and interstitial collagenase, is enhanced, together with the expression of chemoattractants for leukocytes, such as interleukin-8 (IL-8). These events lead to increased connective tissue degradation. We have examined the growth factor regulation of expression in cultured fibroblasts of the prototypic pro-inflammatory factors interstitial collagenase and IL-8. Results: We demonstrate that transforming growth factor-beta (TGF-beta) does not interfere with cytokine-induced IL-8 gene expression, nor does it affect the activity of NF-kappa B-driven promoters. In contrast, TGF-beta down-regulates collagenase gene expression through the induction of the jun-B proto-oncogene. Jun-B is a negative regulator of c-jun, which mediates cytokine activation of collagenase gene expression through its action as a component of the AP-1 transcription factor. Conclusion: Our data suggest that TGF-beta may attenuate the deleterious events that occur in inflammation by preventing cytokine-induced extracellular matrix degradation, although it does not affect cytokine-induced recruitment of pro-inflammatory cells. Furthermore, our data suggest a potential therapeutic use for jun-B, which may be a candidate for gene therapy in disease states that are characterized by excessive connective tissue degradation. C1 NCI,DIV CANC ETIOL,BIOL LAB,TUMOR BIOL SECT,BETHESDA,MD 20892. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,JEFFERSON INST MOLEC MED,DEPT BIOCHEM,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,JEFFERSON INST MOLEC MED,DEPT MOLEC BIOL,PHILADELPHIA,PA 19107. RP MAUVIEL, A (reprint author), THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,JEFFERSON INST MOLEC MED,DEPT DERMATOL,PHILADELPHIA,PA 19107, USA. RI MAUVIEL, Alain/F-6251-2013 NR 51 TC 57 Z9 58 U1 1 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD DEC 1 PY 1993 VL 3 IS 12 BP 822 EP 831 DI 10.1016/0960-9822(93)90216-B PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MT306 UT WOS:A1993MT30600003 PM 15335815 ER PT J AU Hinnebusch, A Hochstrasser, M AF Hinnebusch, Alan Hochstrasser, Mark TI Untitled SO CURRENT OPINION IN CELL BIOLOGY LA English DT Editorial Material C1 [Hinnebusch, Alan] NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. [Hochstrasser, Mark] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA. RP Hinnebusch, A (reprint author), NICHHD, Mol Genet Lab, NIH, Bldg 6B,Room 3B-309, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD DEC PY 1993 VL 5 IS 6 BP 941 EP 943 DI 10.1016/0955-0674(93)90073-Y PG 3 WC Cell Biology SC Cell Biology GA V26EC UT WOS:000208527900002 ER PT J AU FOWLKES, BJ RAMSDELL, F AF FOWLKES, BJ RAMSDELL, F TI T-CELL TOLERANCE SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID THYMIC MEDULLARY EPITHELIUM; IMMATURE CD4+8+ THYMOCYTES; INVITRO CLONAL DELETION; DIFFERENTIAL EXPRESSION; PERIPHERAL TOLERANCE; FAS ANTIGEN; INDUCTION; PEPTIDE; ANERGY; B7 AB As the consequences of autoimmunity are so damaging to an individual, both deletional and non-deletional forms of T-cell tolerance are observed in the thymus as well as the periphery. Although the relationship between these types of tolerance is not clear, recent studies in vivo and in vitro have begun to identify the cellular and molecular interactions involved. Whereas thymic development must account for both positive and negative selection, it is now apparent that T-cell responses in the periphery must also strike a balance between the generation of effector function and activation-induced tolerance. C1 IMMUNEX CORP,DEPT IMMUNOBIOL,SEATTLE,WA. RP FOWLKES, BJ (reprint author), NIAID,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 67 TC 51 Z9 52 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD DEC PY 1993 VL 5 IS 6 BP 873 EP 879 DI 10.1016/0952-7915(93)90099-E PG 7 WC Immunology SC Immunology GA MK359 UT WOS:A1993MK35900003 PM 8297519 ER PT J AU CLORE, GM BAX, A IKURA, M GRONENBORN, AM AF CLORE, GM BAX, A IKURA, M GRONENBORN, AM TI STRUCTURE OF CALMODULIN TARGET PEPTIDE COMPLEXES SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Article ID LIGHT-CHAIN KINASE; X-RAY-SCATTERING; CENTRAL HELIX; BINDING DOMAIN; CONFORMATIONAL CHANGE; MULTIDIMENSIONAL NMR; PHOSPHORYLASE-KINASE; PROTEIN-KINASE; SUBUNIT; SPECTROSCOPY AB The structures of the complexes between calcium-bound calmodulin and synthetic peptides comprising the calmodulin-binding domain of skeletal and smooth muscle myosin light-chain kinase have now been solved by NMR and X-ray crystallography, respectively. Within coordinate errors, there are no significant differences between the two structures. The two domains of calmodulin (residues 6-73 and 83-146) remain essentially unchanged upon complexation. The long central helix (residues 65-93) which connects the two domains in the crystal structure of calcium-bound calmodulin, however, is disrupted in the complex into two helices connected by a long flexible loop (residues 74-82), thereby enabling the two domains to clamp the bound peptide which adopts a helical conformation. The overall structure of the complex is globular, approximating an ellipsoid of dimensions 47 x 32 x 30 angstrom The helical peptide is located in a hydrophobic channel which passes through the center of the ellipsoid at an angle of 45-degrees to its long axis. RP CLORE, GM (reprint author), NIDDKD,CHEM PHYS LAB,BLDG 5,BETHESDA,MD 20892, USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 36 TC 46 Z9 47 U1 0 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD DEC PY 1993 VL 3 IS 6 BP 838 EP 845 DI 10.1016/0959-440X(93)90146-C PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MN447 UT WOS:A1993MN44700004 ER PT J AU RICHTERS, JE CICCHETTI, D AF RICHTERS, JE CICCHETTI, D TI TOWARD A DEVELOPMENTAL PERSPECTIVE ON CONDUCT DISORDER SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Editorial Material C1 UNIV ROCHESTER,MT HOPE FAMILY CTR,ROCHESTER,NY 14627. RP RICHTERS, JE (reprint author), NIMH,CHILD & ADOLESCENT DISORDERS RES BRANCH,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 14 TC 34 Z9 34 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD WIN-SPR PY 1993 VL 5 IS 1-2 BP 1 EP 4 DI 10.1017/S0954579400004223 PG 4 WC Psychology, Developmental SC Psychology GA LJ431 UT WOS:A1993LJ43100001 ER PT J AU RICHTERS, JE CICCHETTI, D AF RICHTERS, JE CICCHETTI, D TI TWAIN,MARK MEETS DSM-III-R - CONDUCT DISORDER, DEVELOPMENT, AND THE CONCEPT OF HARMFUL DYSFUNCTION SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Review ID ATTENTION-DEFICIT DISORDER; ATTACHMENT RELATIONSHIPS; RESPONSE PERSEVERATION; INDIVIDUAL-DIFFERENCES; JUVENILE-DELINQUENCY; BEHAVIOR DISORDERS; AGGRESSION; PSYCHOPATHOLOGY; HYPERACTIVITY; CHILDREN AB The Diagnostic and Statistical Manual (3rd ed., rev.) (DSM-III-R) diagnosis of conduct disorder assumes that all children who engage in three or more criterion antisocial behaviors for 6 months or more suffer from a mental disorder. It resists all contextual information about a child's developmental history, capacities strengths and circumstances, and assumes that the antisocial behavior necessarily stems from an underlying disorder. In this review, we use Mark Twain's narrative of the lives of Tom Sawyer and Huckleberry Finn as a point of departure for questioning the reasonableness of this assumption, and for examining normal as well as pathological pathways to antisocial behavior. We begin by reviewing the status of earlier controversies about the mental disorder concept in the service of documenting the impressive progress of the field in conceptualizing disorder. Next, we examine Wakefield's (1992a, 1992b) recently introduced ''harmful dysfunction'' concept of mental disorder and employ its criteria to evaluate the hypothesis that chronic antisocial behavior in childhood as defined by DSM-III-R is caused by an underlying mental disorder. We also examine some of the difficulties in discriminating between disorder- and nondisorder-based antisocial behavior, and consider issues that warrant attention in future theoretical and empirical work. Finally, we explore the pragmatic rather than scientific basis for DSM-III-R's mental disorder claim and argue that regardless of its status as a mental disorder, this most troubling and harmful behavior syndrome of childhood deserves the intensive interest, concern, and resources of the scientific and public health communities. C1 UNIV ROCHESTER,MT HOPE FAMILY CTR,ROCHESTER,NY 14627. RP RICHTERS, JE (reprint author), NIMH,CHILD & ADOLESCENT DISORDERS RES BRANCH,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 117 TC 111 Z9 111 U1 2 U2 96 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD WIN-SPR PY 1993 VL 5 IS 1-2 BP 5 EP 29 DI 10.1017/S0954579400004235 PG 25 WC Psychology, Developmental SC Psychology GA LJ431 UT WOS:A1993LJ43100002 ER PT J AU ZAHNWAXLER, C AF ZAHNWAXLER, C TI WARRIORS AND WORRIERS - GENDER AND PSYCHOPATHOLOGY SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID SEX-DIFFERENCES; CHILDHOOD PSYCHOPATHOLOGY; CONDUCT DISORDER; FOLLOW-UP; SOCIALIZATION; PREDICTORS; AGGRESSION; PATTERNS; CHILDREN; EMPATHY AB Antisocial behaviors in females may differ from more prototypically ''male'' patterns of aggression, violence, and criminality that dominate criteria for conduct problems in diagnostic systems. This raises questions of how to define and investigate conduct problems in females as well as how to identify differential childhood antecedents. A developmental psychopathology perspective is advanced as one useful approach to understanding adaptive and maladaptive social patterns in males and females that may lead to different developmental trajectories and influence the forms of psychopathology that develop. The utility of de-emphasizing serious physical aggression as one important criteria for conduct problems is questioned. Recommendations that particular forms of deviance in females be considered as markers of their antisocial patterns (e.g., somatic complaints, friendlessness, underachievement) are also called into question. Rather than adopt sex-specific criteria to assess conduct problems, it is necessary to expand and broaden the diagnostic categories to include serious externalizing problems regardless of whether they occur in males or females. RP ZAHNWAXLER, C (reprint author), NIMH,BLDG 15K,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 46 TC 208 Z9 209 U1 5 U2 17 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD WIN-SPR PY 1993 VL 5 IS 1-2 BP 79 EP 89 DI 10.1017/S0954579400004272 PG 11 WC Psychology, Developmental SC Psychology GA LJ431 UT WOS:A1993LJ43100006 ER PT J AU CICCHETTI, D RICHTERS, JE AF CICCHETTI, D RICHTERS, JE TI DEVELOPMENTAL CONSIDERATIONS IN THE INVESTIGATION OF CONDUCT DISORDER SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID ANTISOCIAL-BEHAVIOR; DELINQUENCY; PREDICTORS; CHILDHOOD; CHILDREN C1 NIMH,CHILD & ADOLESCENT DISORDERS RES BRANCH,BETHESDA,MD 20892. RP CICCHETTI, D (reprint author), UNIV ROCHESTER,MT HOPE FAMILY CTR,ROCHESTER,NY 14627, USA. NR 72 TC 50 Z9 50 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD WIN-SPR PY 1993 VL 5 IS 1-2 BP 331 EP 344 DI 10.1017/S0954579400004429 PG 14 WC Psychology, Developmental SC Psychology GA LJ431 UT WOS:A1993LJ43100021 ER PT J AU TIRONE, E SIRACUSA, G HASCALL, VC FRAJESE, G SALUSTRI, A AF TIRONE, E SIRACUSA, G HASCALL, VC FRAJESE, G SALUSTRI, A TI OOCYTES PRESERVE THE ABILITY OF MOUSE CUMULUS CELLS IN CULTURE TO SYNTHESIZE HYALURONIC-ACID AND DERMATAN SULFATE SO DEVELOPMENTAL BIOLOGY LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; HUMAN CHORIONIC-GONADOTROPIN; CHAIN CLEAVAGE CYTOCHROME-P-450; MURAL GRANULOSA-CELLS; PREOVULATORY FOLLICLE; RAT; INVITRO; DIFFERENTIATION; EXPRESSION; EXPANSION C1 UNIV ROMA TOR VERGATA, DEPT PUBL HLTH & CELL BIOL, HISTOL & EMBRYOL SECT, I-00173 ROME, ITALY. NIDR, BONE RES BRANCH, BETHESDA, MD 20892 USA. UNIV ROMA TOR VERGATA, DEPT INTERNAL MED, I-00173 ROME, ITALY. OI SALUSTRI, ANTONIETTA/0000-0002-8731-1041 NR 25 TC 13 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 EI 1095-564X J9 DEV BIOL JI Dev. Biol. PD DEC PY 1993 VL 160 IS 2 BP 405 EP 412 DI 10.1006/dbio.1993.1316 PG 8 WC Developmental Biology SC Developmental Biology GA ML355 UT WOS:A1993ML35500009 PM 8253273 ER PT J AU IMAOKA, S OGAWA, H KIMURA, S GONZALEZ, FJ AF IMAOKA, S OGAWA, H KIMURA, S GONZALEZ, FJ TI COMPLETE CDNA SEQUENCE AND CDNA-DIRECTED EXPRESSION OF CYP4A11, A FATTY-ACID OMEGA-HYDROXYLASE EXPRESSED IN HUMAN KIDNEY SO DNA AND CELL BIOLOGY LA English DT Article ID FAMILIAL AMYLOIDOTIC POLYNEUROPATHY; HYPERTENSIVE RATS; CYTOCHROME-P450; IDENTIFICATION; BACULOVIRUS; SUBFAMILY; GENES AB A cDNA was isolated from a human kidney lambda gt10 library using the rat CYP4A3 cDNA as a probe. The cDNA-deduced amino acid sequence encoded a protein of 519 amino acids that was designated CYP4A11 (Nelson et al., 1993) and exhibited 76%, 72%, 80%, and 53% similarities to rat CYP4A1, rat CYP4A3, rabbit CYP4A6, and human CYP4B1, respectively. The deduced amino-terminal amino acid sequence of this cDNA agreed with the amino-terminal amino acid sequence of a major P450 protein purified from human renal microsomes. A second variant form of CYP4A11 cDNA, designated CYP4A11v, was isolated from the same library and had a deletion of a single adenine residue, thereby extending the reading frame and resulting in a protein of 591 amino acids. CYP4A11v Is probably encoded by a rare allelic variant of CYP4A11, since no mutant alleles were uncovered in 15 normal individuals, as determined by a polymerase chain reaction (PCR) diagnostic test. Baculovirus-mediated cDNA expression of CYP4A11 yielded a P450 protein having a lambda max of 452 nm when reduced and complexed with carbon monoxide. The expressed enzyme efficiently catalyzed omega-hydroxylation of lauric acid. No detectable activity was uncovered toward arachidonic acid and prostaglandin E(1). The cDNA-expressed variant, CYP4A11v, was found to be unstable and not to efficiently metabolize lauric acid, as assessed by both baculovirus and monkey kidney COS cell cDNA expression systems. These studies indicate that CYP4A11 is a major fatty acid-metabolizing P450 that is expressed in human kidney. C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 24 TC 59 Z9 62 U1 0 U2 1 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 DEC PY 1993 VL 12 IS 10 BP 893 EP 899 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA MQ469 UT WOS:A1993MQ46900004 PM 8274222 ER PT J AU ALIMZHANOV, MB KUPRASH, DV TURETSKAYA, RL OSIPOVICH, OA BORODULINA, OR OSOVSKAYA, VS CHUMAKOV, PM NEDOSPASOV, SA AF ALIMZHANOV, MB KUPRASH, DV TURETSKAYA, RL OSIPOVICH, OA BORODULINA, OR OSOVSKAYA, VS CHUMAKOV, PM NEDOSPASOV, SA TI CLONING AND CHARACTERIZATION OF CHROMOSOMAL COPY OF THE GENE ENCODING MURINE HOMOLOG OF HUMAN GADD45, A PROTEIN-INDUCED BY DNA-DAMAGE SO DOKLADY AKADEMII NAUK LA Russian DT Article ID ATAXIA-TELANGIECTASIA; P53; CELLS C1 NCI,FREDERICK,MD 21701. RP ALIMZHANOV, MB (reprint author), RUSSIAN ACAD SCI,INST MOLEC BIOL,MOSCOW,RUSSIA. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Kuprash, Dmitry/O-4899-2015; Nedospasov, Sergei/Q-7319-2016 OI Kuprash, Dmitry/0000-0002-1488-4148; NR 14 TC 2 Z9 3 U1 0 U2 0 PU MEZHDUNARODNAYA KNIGA PI MOSCOW PA 39 DIMITROVA UL., 113095 MOSCOW, RUSSIA SN 0869-5652 J9 DOKL AKAD NAUK+ JI Dokl. Akad. Nauk PD DEC PY 1993 VL 333 IS 6 BP 788 EP 791 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MT435 UT WOS:A1993MT43500029 PM 7509226 ER PT J AU HEISHMAN, SJ SNYDER, FR HENNINGFIELD, JE AF HEISHMAN, SJ SNYDER, FR HENNINGFIELD, JE TI PERFORMANCE, SUBJECTIVE, AND PHYSIOLOGICAL-EFFECTS OF NICOTINE IN NONSMOKERS SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE NICOTINE; COGNITIVE PERFORMANCE; SUBJECTIVE EFFECTS; HUMANS; NONSMOKERS ID INFORMATION-PROCESSING PERFORMANCE; CIGARETTE-SMOKING; CHEWING GUM; NONSMOKERS; SCOPOLAMINE; BATTERY; MEMORY AB Sixteen human volunteers with little or no experience using tobacco participated in one 4.5-h experimental session in which they were administered three doses of nicotine polacrilex gum (0, 2 and 4 mg) in ascending order at 90-min intervals. Physiological, subjective, and cognitive performance measures were assessed before and after each dose. Nicotine produced dose-related increases in heart rate and blood pressure and decreases in skin temperature. Nicotine also increased subjective ratings of dose strength and negative effects and decreased ratings of desire to repeat the same dose. There were dose-related trends toward decreased accuracy and increased response time on 3 of the 4 cognitive tests. These data do not support the hypothesis that nicotine enhances cognitive functioning in non-smokers. RP HEISHMAN, SJ (reprint author), NATL INST DRUG ABUSE,ADDICT RES CTR,CLIN PHARMACOL BRANCH,BALTIMORE,MD 21224, USA. NR 37 TC 52 Z9 52 U1 2 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD DEC PY 1993 VL 34 IS 1 BP 11 EP 18 DI 10.1016/0376-8716(93)90041-N PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA MT590 UT WOS:A1993MT59000002 PM 8174498 ER PT J AU TIFFANY, ST SINGLETON, E HAERTZEN, CA HENNINGFIELD, JE AF TIFFANY, ST SINGLETON, E HAERTZEN, CA HENNINGFIELD, JE TI THE DEVELOPMENT OF A COCAINE CRAVING QUESTIONNAIRE SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE CRAVING; URGES; COCAINE; QUESTIONNAIRE ID ABSTINENCE; URGES; DESIPRAMINE; DEPENDENCE AB Two versions of a 45-item questionnaire on cocaine craving were administered to 225 cocaine users. The Now version asked about current craving for cocaine, and the General version asked about average craving over the preceding week. Factor analyses showed that a four-factor solution best described the item structure for both versions of the questionnaire. Higher-order analyses indicated that each version was permeated by a single second-order factor. Factor scales derived for each primary and second-order factor had moderate to high reliabilities. Examination of item content, correlations of factors across versions, and external correlates of the factors suggested that both versions were represented by the same hierarchical factor structure. The theoretical and clinical implications of the results from these craving instruments are discussed. C1 NATL INST DRUG ABUSE,ADDICT RES CTR,BALTIMORE,MD 21224. RP TIFFANY, ST (reprint author), PURDUE UNIV,DEPT PSYCHOL SCI,W LAFAYETTE,IN 47907, USA. OI Singleton, Edward G./0000-0003-3442-877X NR 26 TC 224 Z9 229 U1 2 U2 9 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD DEC PY 1993 VL 34 IS 1 BP 19 EP 28 DI 10.1016/0376-8716(93)90042-O PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA MT590 UT WOS:A1993MT59000003 PM 8174499 ER PT J AU MALHOTRA, AK LITMAN, RE PICKAR, D AF MALHOTRA, AK LITMAN, RE PICKAR, D TI ADVERSE-EFFECTS OF ANTIPSYCHOTIC-DRUGS SO DRUG SAFETY LA English DT Review AB Since the introduction of chlorpromazine in the 1950s, neuroleptic medications have been the mainstay of treatment of schizophrenia and other psychotic disorders. These medications do not always lead to complete remission of symptoms but they have allowed many patients to lead more productive and satisfying lives away from the restrictions of chronic hospitalisation. However, neuroleptics are associated with a number of adverse effects that can compromise their effectiveness. Extrapyramidal adverse effects include acute dystonic reactions, neuroleptic-induced Parkinsonism and akathisia. They can often be treated with neuroleptic dose reduction, addition of anticholinergic or beta-blocking agents, or medication change. Later-onset movement disorders such as tardive dyskinesia or dystonia require careful evaluation and may be treated with dose reduction or change of neuroleptic to an atypical agent. Potentially fatal reactions such as agranulocytosis and neuroleptic malignant syndrome can rarely occur and often require significant medical intervention. Clozapine offers some advantages over 'typical' neuroleptics but has a unique adverse effect profile which includes agranulocytosis. RP MALHOTRA, AK (reprint author), NIMH,EXPTL THERAPEUT BRANCH,NIH BLDG 10-4N214,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 31 Z9 32 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PD DEC PY 1993 VL 9 IS 6 BP 429 EP 436 PG 8 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA ML922 UT WOS:A1993ML92200004 PM 7907481 ER PT J AU WASSERMANN, EM PASCUALLEONE, A VALLSSOLE, J TORO, C COHEN, LG HALLETT, M AF WASSERMANN, EM PASCUALLEONE, A VALLSSOLE, J TORO, C COHEN, LG HALLETT, M TI TOPOGRAPHY OF THE INHIBITORY AND EXCITATORY RESPONSES TO TRANSCRANIAL MAGNETIC STIMULATION IN A HAND MUSCLE SO ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE TRANSCRANIAL MAGNETIC STIMULATION; INHIBITION; MOTOR CORTEX; (HUMAN) ID HUMAN MOTOR CORTEX; DISTAL FORELIMB MUSCLES; INTRACORTICAL STIMULATION; ELECTRICAL-STIMULATION; DISYNAPTIC INHIBITION; CORTICAL STIMULATION; SPINAL MOTONEURONS; 2 REPRESENTATIONS; UNIT RESPONSES; MONKEY AB We studied the excitatory motor evoked potentials (MEPs) and the inhibitory (silent period) responses to focal transcranial magnetic stimulation (TMS) in the abductor pollicis brevis (APB) of 5 normal subjects to learn whether the scalp topography of the two responses differed. At the scalp location where stimulation produced the highest-amplitude MEP in the voluntarily activated APB, stimulus intensities below the MEP threshold produced silent periods with little or no preceding facilitation. The silent periods had a mean duration of 26.8 +/- 6.8 msec and a mean onset latency of 27.6 +/- 3.6 msec, which was 7.2 +/- 2.3 msec longer than the latency of MEPs produced in the APB by higher stimulus intensities. A period of excitation, with an onset latency of 50-80 msec, often followed the silent period. On averaged trials, a stimulus intensity just above the threshold of the MEP at its optimal position produced MEPs followed by silent periods at a cluster of scalp locations 1 cm apart on the central scalp (medial area) and silent periods with very slight or no preceding facilitation in 3-9 locations lateral to the MEP area (lateral area). This finding was confirmed in 3 subjects with maps constructed from statistical analysis of multiple trials. These maps also showed that MEPs produced from the medial area occurred 4-6 msec earlier than those produced from the lateral area. The integral of the silent period tended to be larger in the lateral area. The motor representation of APB, as defined by TMS, is not homogeneous but rather contains at least two components that differ physiologically and topographically. RP WASSERMANN, EM (reprint author), NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,HUMAN CORT PHYSIOL UNIT,BLDG 10,BETHESDA,MD 20892, USA. RI Pascual-Leone, Alvaro/G-6566-2011 NR 37 TC 105 Z9 106 U1 0 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0013-4694 J9 ELECTROEN CLIN NEURO JI Electroencephalogr. Clin. Neurophysiol. PD DEC PY 1993 VL 89 IS 6 BP 424 EP 433 DI 10.1016/0168-5597(93)90116-7 PG 10 WC Engineering, Biomedical; Clinical Neurology SC Engineering; Neurosciences & Neurology GA MR557 UT WOS:A1993MR55700008 PM 7507429 ER PT J AU CHRAMBACH, A AF CHRAMBACH, A TI HOW FAR HAVE WE PROGRESSED TOWARD AUTOMATED ELECTROPHORESIS IN SIEVING MEDIA OF THE 21ST CENTURY SO ELECTROPHORESIS LA English DT Article; Proceedings Paper CT 1st International Meeting of the International-Council-of-Electrophoresis-Societies (ICES) CY JUN 02-04, 1993 CL SANDEFJORD, NORWAY SP INT COUNCIL ELECTROPHORESIS SOC ID POLYACRYLAMIDE-GEL ELECTROPHORESIS; CONVEX FERGUSON PLOTS; PORE GRADIENT GEL; DNA FRAGMENTS; CAPILLARY ELECTROPHORESIS; AGAROSE-GEL; MOBILITY; CONFORMATION; SEPARATION; DENSITY AB The automation of electrophoresis in polymeric sieving media requires (i) an objective definition of the conditions (the polymer, its concentration, solvent, buffer, pH, ionic strength, temperature) under which a particular separation proceeds most effectively; (ii) apparatus capable of zone detection, acquisition by computer, evaluation (migration distance, zone width and area) and a printout of the number of components, their size and net charge, and the polymer conditions under which each component separates most effectively from its two neighboring zones. Both of these prerequisites of automation have been met to a first approximation at this time and, after further maturation, assembly and streamlining should be able to fill the need of the coming century for a more efficient, nonarbitrary and cost-effective mode of macromolecular and cellular particle separation. (i) The realization of the qualitative equivalence of polymer solutions and gels has greatly increased our options in the choice of sieving media. That choice can be made objectively by correlating separation efficiency (S), particle size (R) and intrinsic viscosity (eta(o)) of the polymer. (S) is a function of the slope, K-R(R), of the Ferguson plot [log(mobility) vs, polymer concentration], or with nonlinear plots (DNA, agarose) K-R(R,T), K-R is at present most easily derived from transverse pore gradient gels or by conducting capillary zone electrophoresis (CZE) at multiple polymer concentrations. Pore gradient CZE appears promising. CZE also defines the free mobility unequivocally. Computer programs exist to generate K-R from migration distances (times), and optimal S and polymer concentration for a particular R from K-R. Optimal S can be related objectively with eta(o) to define, as a first-order approximation, the optimal polymer for the separation within a narrow R-range. (ii) Apparatus with automated detection of zones and acquisition of migration distances has become commercially available (e.g. Applied Biosystems, Du Pont, LabIntelligence). One of these scans multiple lanes and can be interfaced to compute K-R and S. Thus, all elements necessary for automated electrophoretic separation under optimally effective separation conditions are available in rudimentary form. Their development, assembly, integration and streamlining should be feasible prior to the onset of the next century. RP CHRAMBACH, A (reprint author), NICHHD,THEORET & PHYS BIOL LAB,MACROMOLEC ANAL SECT,BLDG 10,RM 6C-101,BETHESDA,MD 20892, USA. NR 45 TC 8 Z9 8 U1 0 U2 2 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD DEC PY 1993 VL 14 IS 12 BP 1250 EP 1254 DI 10.1002/elps.11501401189 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA MV668 UT WOS:A1993MV66800003 PM 8137784 ER PT J AU LEMKIN, PF WU, YC UPTON, K AF LEMKIN, PF WU, YC UPTON, K TI AN EFFICIENT DISK BASED DATA STRUCTURE FOR RAPID SEARCHING OF QUANTITATIVE 2-DIMENSIONAL GEL DATABASES SO ELECTROPHORESIS LA English DT Article; Proceedings Paper CT 1st International Meeting of the International-Council-of-Electrophoresis-Societies (ICES) CY JUN 02-04, 1993 CL SANDEFJORD, NORWAY SP INT COUNCIL ELECTROPHORESIS SOC AB Fast access of two-dimensional (2-D) gel quantitative databases is important for rapid searching for protein differences between sets of 2-D gels from an experiment. The GELLAB-II system organizes corresponding spots from the gels in the database into reference or ''Rspot'' sets. These Rspot numeric names index fixed regions in the paged composite gel database file. This is adequate for an existing database, but has several problems. (i) Building the initial database requires guessing how much disk space to pre-allocate for each corresponding spot (i.e. spots from different gels). If it ever runs out of preallocated space during this process, it must expand the size of each corresponding set of spots copying the old database data into the new in-place on the disk. (ii) When adding new gels or editing the database, if a new spot is created, the system may also go into this expansion mode. The time spent and wasted disk space can be appreciable - depending on the size of the database (order of 100 gel database). (iii) Because each set of corresponding spots is the same size, we waste space in most spot sets since they do not require the additional space a few spot sets require which contain additional fragmented spots. We present a new low-level disk object-based structure and algorithm, paged indexed buckets (PIB), which optimizes disk space usage while having similar retrieval speed to the original method. C1 CSPI,SCANALYT,BILLERICA,MA. FCRDC,PROGRAM RESOURCES INC,FREDERICK,MD. RP LEMKIN, PF (reprint author), NCI,FCRDC,LMMB,IMAGE PROC SECT,BLDG 469,RM 150,BOX B,FREDERICK,MD 21702, USA. NR 7 TC 4 Z9 4 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD DEC PY 1993 VL 14 IS 12 BP 1341 EP 1350 DI 10.1002/elps.11501401207 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA MV668 UT WOS:A1993MV66800021 PM 8137800 ER PT J AU WU, YC LEMKIN, PF UPTON, K AF WU, YC LEMKIN, PF UPTON, K TI A FAST SPOT SEGMENTATION ALGORITHM FOR 2-DIMENSIONAL GEL-ELECTROPHORESIS ANALYSIS SO ELECTROPHORESIS LA English DT Article; Proceedings Paper CT 1st International Meeting of the International-Council-of-Electrophoresis-Societies (ICES) CY JUN 02-04, 1993 CL SANDEFJORD, NORWAY SP INT COUNCIL ELECTROPHORESIS SOC ID COMPUTER-ANALYSIS; 2-DIMENSIONAL ELECTROPHORESIS; PROTEINS AB An important issue in the automation of two-dimensional gel electrophoresis image analysis is the detection and quantification of protein spots. A spot segmentation algorithm must detect, define the extent of, and measure the integrated density of spots under a wide variety of actual gel image conditions. Besides these functions, the algorithm must be memory efficient to be able to process very large gel images and do this in a reasonable amount of computation time on low-cost computers, such as workstations and personal computers. We have developed a fast spot segmentation algorithm, extending the GELLAB-II segmenter, which extracts spots in a single raster scanning pass through the gel image. The performance analysis of the algorithm will be given in the paper as well as a discussion of the algorithm. C1 NCI,FCRDC,IMAGE PROC SECT,FREDERICK,MD. FCRDC,PROGRAM RESOURCES INC,FREDERICK,MD. RP WU, YC (reprint author), CSPI,SCANALYT,40 LINNELL CIRCLE,BILLERICA,MA 01821, USA. NR 19 TC 13 Z9 13 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD DEC PY 1993 VL 14 IS 12 BP 1351 EP 1356 DI 10.1002/elps.11501401208 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA MV668 UT WOS:A1993MV66800022 PM 8137801 ER PT J AU MUKHOPADHYAY, G CARR, KM KAGUNI, JM CHATTORAJ, DK AF MUKHOPADHYAY, G CARR, KM KAGUNI, JM CHATTORAJ, DK TI OPEN-COMPLEX FORMATION BY THE HOST INITIATOR, DNAA, AT THE ORIGIN OF P1 PLASMID REPLICATION SO EMBO JOURNAL LA English DT Article DE DNAA; DNA PROTEIN INTERACTIONS; DNA REPLICATION; PLASMID; REPA ID COPY NUMBER CONTROL; ESCHERICHIA-COLI; PROTEIN; BINDING; REPA; INVITRO; INVIVO; BOX; TRANSCRIPTION; PURIFICATION AB Replication of P1 plasmid requires both the plasmid-specific initiator, RepA, and the host initiator, DnaA. Here we show that DnaA can make the P1 origin reactive to the single-strand specific reagents KMnO4 and mung bean nuclease. Addition of RepA further increased the KMnO4 reactivity of the origin, although RepA alone did not influence the reaction. The increased reactivity implies that the two initiators interact in some way to alter the origin conformation. The KMnO4 reactivity was restricted to one strand of the origin. We suggest that the roles of DnaA in P1 plasmid and bacterial replication are similar: origin opening and loading of the DnaB helicase. The strand-bias in chemical reactivity at the P1 origin most likely indicates that only one of the strands is used for the loading of DnaB, a scenario consistent with the unidirectional replication of the plasmid. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. MICHIGAN STATE UNIV,DEPT BIOCHEM,E LANSING,MI 48824. OI Kaguni, Jon/0000-0002-3096-4447 FU NIGMS NIH HHS [R01 GM033992] NR 38 TC 41 Z9 42 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 1 PY 1993 VL 12 IS 12 BP 4547 EP 4554 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MF994 UT WOS:A1993MF99400009 PM 8223464 ER PT J AU SEGALL, AM NASH, HA AF SEGALL, AM NASH, HA TI SYNAPTIC INTERMEDIATES IN BACTERIOPHAGE-LAMBDA SITE-SPECIFIC RECOMBINATION - INTEGRASE CAN ALIGN PAIRS OF ATTACHMENT SITES SO EMBO JOURNAL LA English DT Article DE BACTERIOPHAGE LAMBDA; INTEGRASE; SITE-SPECIFIC RECOMBINATION; SYNAPTIC COMPLEXES ID POLYACRYLAMIDE-GEL ELECTROPHORESIS; PROTEIN-DNA COMPLEX; COLI IHF PROTEIN; FLP RECOMBINASE; BINDING-SITES; INT PROTEIN; MUTATIONAL ANALYSIS; STRAND EXCHANGE; XIS PROTEIN; ATT SITE AB Bacteriophage lambda uses site-specific recombination to move its DNA into and out of the Escherichia coli genome. The recombination event is mediated by the recombinase integrase (Int) together with several accessory proteins through short specific DNA sequences known as attachment sites. A gel mobility shift assay has been used to show that, in the absence of accessory proteins, Int can align and hold together two DNA molecules, each with an attachment site, to form stable non-covalent 'bimolecular complexes'. Each attachment site must have both core and arm binding sites for Int to participate in a bimolecular complex. These stable structures can be formed between pairs of attL and attP attachment sites, but cannot include attB or attR sites; they are inhibited by integration host factor (IHF) protein. The bimolecular complexes are shown to represent a synaptic intermediate in the reaction in which Int protein promotes the IHF-independent recombination of two attL sites. These complexes should enable a detailed analysis of synapsis for this pathway. RP SEGALL, AM (reprint author), NIMH,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 54 TC 32 Z9 32 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 1 PY 1993 VL 12 IS 12 BP 4567 EP 4576 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MF994 UT WOS:A1993MF99400011 PM 8223466 ER PT J AU RICE, NR ERNST, MK AF RICE, NR ERNST, MK TI IN-VIVO CONTROL OF NF-KAPPA-B ACTIVATION BY I-KAPPA-B-ALPHA SO EMBO JOURNAL LA English DT Article DE C-REL; I-ALEPH-B-ALPHA; NF-ALEPH-B; TRANSCRIPTION FACTOR; REGULATORY COMPLEXES ID DNA-BINDING SUBUNIT; NECROSIS-FACTOR-ALPHA; REL-ASSOCIATED PP40; TRANSCRIPTION FACTOR; V-REL; P65 SUBUNIT; 65-KD SUBUNIT; PHORBOL ESTER; P50 SUBUNIT; PROTEIN AB The transcription factor NF-chiB is stored in the cytoplasm in complexes with the inhibitor protein IchiBalpha. It has been shown in vitro that dissociation of IchiBalpha from these complexes results in active NF-chiB. In this report we show that lipopolysaccharide (LPS)-induced activation of B or pre-B cells results in loss of IchiBalpha from NF-chiB complexes in vivo. Many liberated NF-chiB dimers reached the nucleus, where increased c-rel, p65 and p50 were detected by immunoblotting and by DNA binding assays. Some liberated dimers were retained in the cytoplasm, however, through binding to newly synthesized IchiBalpha, a finding which strongly suggests (i) that the LPS-induced signal causes dissociation of complexes rather than preventing their association and (ii) that dissociation results from modification of IchiBalpha and not of c-rel or p65. No effect of LPS treatment was detected on p105 or p100, which also retain rel family members in the cytoplasm. Quite unexpectedly, we also found that in unstimulated cells there is a constant ongoing process of degradation and replacement of complexed IchiBalpha. We propose that this turnover results in the low level of active NF-chiB presumably necessary even in the unstimulated cell, and that the high rate of synthesis of IchiBalpha provides the ability to turn off NF-chiB activity rapidly as soon as the activating signal ceases. RP RICE, NR (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC VIROL & CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101] NR 54 TC 312 Z9 313 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 1 PY 1993 VL 12 IS 12 BP 4685 EP 4695 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MF994 UT WOS:A1993MF99400023 PM 8223478 ER PT J AU GERSHON, PD MOSS, B AF GERSHON, PD MOSS, B TI URIDYLATE-CONTAINING RNA SEQUENCES DETERMINE SPECIFICITY FOR BINDING AND POLYADENYLATION BY THE CATALYTIC SUBUNIT OF VACCINIA VIRUS POLY(A) POLYMERASE SO EMBO JOURNAL LA English DT Article DE MESSENGER RNA; POLY(A) POLYMERASE; POLY(A) TAIL; RNA RECOGNITION; VACCINIA ID MESSENGER-RNA; PROTEIN; DOWNSTREAM; DOMAIN; TRANSCRIPTION; VIRIONS; CLONING AB VP55, the catalytic subunit of vaccinia virus poly(A) polymerase, has the remarkable property of adding 30-35 adenylates to RNA 3' ends' in a rapid processive burst before an abrupt transition to slow, non-processive adenylate addition. Here, we demonstrate that this property results from the affinity of the enzyme for uridylate residues within the 3' 31-40 nt of the RNA primer. At physiological salt concentrations, both polyadenylation and stable VP55 binding required the presence of multiple uridylates within a 31-40 nt length of RNA, though specific RNA sequences were not necessary. Even DNA in which the deoxythymidylate residues were replaced with ribouridylates, could be polyadenylated in a processive manner. Both the unmethylated pyrimidine ring and a 2'-OH on the associated sugar are features of ribouridylates that are important for priming. The abrupt termination of processive polyadenylation was attributed to translocation of VP55 along the nascent poly(A) tail, which lacks uridylates for stable binding. As evidence for translocation and interaction with newly synthesized RNA, other homopolymer tails were synthesized by VP55 in the presence of Mn2+, which relaxes its donor nucleotide specificity. Only during poly(U) tan synthesis did processive nucleotide addition fail to terminate. RP GERSHON, PD (reprint author), NIAID,VIRAL DIS LAB,BETHESDA,MD 20892, USA. NR 24 TC 25 Z9 25 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 1 PY 1993 VL 12 IS 12 BP 4705 EP 4714 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MF994 UT WOS:A1993MF99400025 PM 7693457 ER PT J AU LEVIN, HL WEAVER, DC BOEKE, JD AF LEVIN, HL WEAVER, DC BOEKE, JD TI NOVEL GENE-EXPRESSION MECHANISM IN A FISSION YEAST RETROELEMENT - TF1 PROTEINS ARE DERIVED FROM A SINGLE PRIMARY TRANSLATION PRODUCT SO EMBO JOURNAL LA English DT Article DE NMT1 PROMOTER; RETROTRANSPOSITION; RETROTRANSPOSON; SCHIZOSACCHAROMYCES-POMBE; TF1 ID VIRUS-LIKE PARTICLES; SCHIZOSACCHAROMYCES-POMBE; DROSOPHILA-MELANOGASTER; ELEMENT TRANSPOSITION; REVERSE-TRANSCRIPTASE; POLYACRYLAMIDE GELS; TY1 TRANSPOSITION; LEUKEMIA-VIRUS; GAG; COPIA AB In sharp contrast to the single ORF of the Schizosaccharomyces pombe retrotransposon Tf1, retroviruses and most retrotransposons employ two different ORFs to separately encode the Gag and Pol proteins. The different ORFs are thought to allow for overexpression of the Gag protein relative to Pol protein presumed necessary for the assembly of functional retrovirus particles and virus-like particles (VLPs). The results of in vivo experiments designed to detect the transposition of Tf1 show that Tf1 is indeed active and can insert itself into the host genome via a true retrotransposition process Thus, a paradox emerged between the lack of any obvious means of overexpressing Tf1 Gag protein and the demonstrated functionality of the element. Epitope tagging experiments described here confirm that the Tf1 large ORF is intact and that there is no translational or transcriptional mechanism used to overexpress the Tf1 Gag protein. In addition, we used sucrose gradients and antisera specific for Tf1 capsid (CA) and integrase (IN) to show that the Tf1 proteins do assemble into uniform populations of macromolecular particles that also co-sediment with Tf1 reverse transcription products. This evidence suggests that Tf1 proteins form VLPs without using the previously described mechanisms that retroviruses and retrotransposons require to overexpress Gag proteins. C1 NICHHD, BETHESDA, MD 20892 USA. RP JOHNS HOPKINS UNIV, SCH MED, DEPT MOLEC BIOL & GENET, 725 N WOLFE ST, BALTIMORE, MD 21205 USA. FU NCI NIH HHS [CA09139, CA16519] NR 45 TC 46 Z9 46 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD DEC 1 PY 1993 VL 12 IS 12 BP 4885 EP 4895 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MF994 UT WOS:A1993MF99400044 PM 8223497 ER PT J AU LEE, WH BONDY, CA AF LEE, WH BONDY, CA TI ISCHEMIC-INJURY INDUCES BRAIN GLUCOSE-TRANSPORTER GENE-EXPRESSION SO ENDOCRINOLOGY LA English DT Article ID DEVELOPMENTAL REGULATION; PRIMARY CULTURES; GLIAL-CELLS; PROTEIN; IDENTIFICATION; FAMILY AB As neurons rely almost exclusively on glucose as an energy substrate, glucose transport is of critical importance to cerebral function. Two specific facilitative glucose transporters, GT1 and -3, predominate in brain, with the latter exclusively expressed by neurons, whereas GT1 is expressed by astrocytes and vascular elements. Little is known about the regulation of these transporters at the genetic level or the extent to which their expression may change in response to acute or chronic changes in metabolic demands. Thus, we employed in situ hybridization to evaluate changes in glucose transporter gene expression in the rat brain in response to ischemia induced by middle cerebral artery occlusion (MCAO). The most remarkable responses were demonstrated by GT1, which within an hour of ischemic insult demonstrated a global increase in gene expression throughout the forebrain. In the ensuing hours, GT1 expression further intensified and became lateralized to the lesioned hemisphere, with normalization of expression contralaterally. Increased GT1 mRNA levels were found in astroglia and microvessels and were also present in distinct neuronal populations, including the piriform cortex, dentate gyrus, and medial habenula, which normally do not express GT1 mRNA. By 24 h post-MCAO, glial cells of the ipsilateral cortex surrounding the infarct zone still demonstrated elevated GT1 mRNA levels, but expression had returned to baseline in neurons. Interestingly, it was not until GT1 expression had subsided (24 h post-MCAO), that there was a modest increase in neuronal GT3 gene expression in the affected hemisphere. GT2 and GT4 mRNAs were not detected in the rat brain under normal conditions or after ischemia. These data demonstrate that ischemia induces an immediate and sustained increase in brain GT1 gene expression in both glial cells and neurons. This augmentation of GT1 expression could represent a defensive strategy aimed at repletion of the brain's energy stores and stabilization of neuronal membrane potential. C1 NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N 262,BETHESDA,MD 20892. NR 22 TC 88 Z9 94 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1993 VL 133 IS 6 BP 2540 EP 2544 DI 10.1210/en.133.6.2540 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MK151 UT WOS:A1993MK15100019 PM 8243275 ER PT J AU ORTMANN, O WASSMANN, D STOJILKOVIC, SS CATT, KJ SCHULZ, KD EMONS, G AF ORTMANN, O WASSMANN, D STOJILKOVIC, SS CATT, KJ SCHULZ, KD EMONS, G TI OVARIAN-STEROIDS MODULATE ENDOTHELIN-INDUCED LUTEINIZING-HORMONE SECRETION FROM CULTURED RAT PITUITARY-CELLS SO ENDOCRINOLOGY LA English DT Article ID GONADOTROPIN-SECRETION; PROGESTERONE; RELEASE; RECEPTORS; ESTRADIOL; CALCIUM; LH; HYPOTHALAMUS; PROLACTIN; ESTROGEN AB It has been demonstrated that endothelins (ETs) induce LH secretory responses in cultured rat pituitary cells. Because estradiol and progesterone are known to be potent modulators of GnRH-induced gonadotropin secretion, we examined whether these steroids also influence the secretory responses of gonadotrophs to ETs. Cultured female rat pituitary cells were treated for 48 h with vehicle (0.2% ethanol), 1 nm estradiol alone, or a combination of 1 nm estradiol and 100 nm progesterone or for 48 h with 1 nm estradiol and a further 4 h with 100 nm progesterone and subsequently stimulated with 10 pm-100 nm ET-1 or ET-3. Forty-eight-hour estradiol treatment led to enhanced LH secretory responses to both ETs. This action was facilitated by short term progesterone treatment (3-fold vs. vehicle), while long term progesterone treatment was inhibitory. Perifusion experiments were performed to study the kinetics of individual and pulsatile LH secretory responses after steroid exposure of pituitary cells. ET-1 induced immediate biphasic LH responses that were augmented by long term estradiol treatment. Two-hour progesterone exposure led to marked increases in LH secretion, whereas 48-h progesterone treatment was inhibitory. Estradiol and progesterone were able to modulate both the initial spike and the secondary plateau phase of the secretory profile in response to ET-1, although these actions did not always reach statistical significance. The steroid treatment paradigms employed also induced inhibitory and stimulatory effects in cells that were stimulated with ET-3 in a pulsatile fashion. In these experiments it could be demonstrated that the facilitatory action of progesterone was present after 50 min of treatment and was maximum after 150 min (5-fold enhancement). The present data support the hypothesis that ETs are involved in the physiological regulation of gonadotropin secretion and demonstrate that ovarian steroids can act as potent modulators of ET-induced LH secretion. C1 PHILIPPS UNIV,DEPT OBSTET & GYNECOL,D-35037 MARBURG,GERMANY. NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. NR 29 TC 18 Z9 18 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1993 VL 133 IS 6 BP 2632 EP 2638 DI 10.1210/en.133.6.2632 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MK151 UT WOS:A1993MK15100032 PM 8243286 ER PT J AU MERCHENTHALER, I AF MERCHENTHALER, I TI INDUCTION OF ENKEPHALIN IN TUBEROINFUNDIBULAR DOPAMINERGIC-NEURONS DURING LACTATION SO ENDOCRINOLOGY LA English DT Article ID ENDOGENOUS OPIOID-PEPTIDES; HYPOPHYSEAL PORTAL BLOOD; PROLACTIN SECRETION; LUTEINIZING-HORMONE; MEDIAN-EMINENCE; BETA-ENDORPHIN; OPIATE RECEPTORS; PREOPTIC AREA; RAT-BRAIN; MORPHINE AB Single- and double-labeling immunocytochemistry was used to demonstrate that the tuberoinfundibular dopaminergic (TIDA) neurons of lactating rats, in contrast to those of male or female rats on any day of the estrous cycle, synthesize enkephalin which is colocalized with dopamine. Each enkephalin-immunopositive perikaryon in the dorsomedial and ventrolateral subdivisions of the arcuate nucleus contains dopamine; therefore, the median eminence of lactating rats contains high levels of enkephalin compared to male or female rats. It has been shown that endogenous opiates, including enkephalin, stimulate PRL secretion by reversing the inhibitory action of dopamine at the level of the TIDA neurons. The present findings suggest that enkephalin, coproduced with dopamine in TIDA neurons of lactating rats, may be an endogenous source for this action and maintain elevated PRL and milk secretion during the nonsuckling periods of lactation. RP MERCHENTHALER, I (reprint author), NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,FUNCT MORPHOL SECT,MD C4-07,RES TRIANGLE PK,NC 27709, USA. NR 53 TC 32 Z9 32 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1993 VL 133 IS 6 BP 2645 EP 2651 DI 10.1210/en.133.6.2645 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MK151 UT WOS:A1993MK15100034 PM 7694844 ER PT J AU CROWLEY, RS INSEL, TR OKEEFE, JA AMICO, JA AF CROWLEY, RS INSEL, TR OKEEFE, JA AMICO, JA TI CYTOPLASMIC OXYTOCIN AND VASOPRESSIN GENE TRANSCRIPTS DECLINE POSTPARTUM IN THE HYPOTHALAMUS OF THE LACTATING RAT SO ENDOCRINOLOGY LA English DT Article ID MESSENGER-RNA; OVARIAN-STEROIDS; SECRETION; ESTROGEN; PROMOTER; NEURONS AB Oxytocin (OT) and vasopressin (AVP) gene expression are enhanced in the rat hypothalamus in late gestation and during the second and third weeks of lactation. We report that during the first 3 postpartum days, OT and AVP cytoplasmic mRNAs in the supraoptic and paraventricular nuclei of lactating rats decreased dramatically, reaching less than one fifth of peak gestational levels by day 2 postpartum. Differences in the temporal pattern of OT and AVP expression were observed in the supraoptic and paraventricular nuclei from days 4-10 of lactation. We also compared OT and AVP cytoplasmic mRNAs isolated from the hypothalamus of day 3 lactating rats to cohorts that had litters removed at the time of parturition. Lactating rats had significantly lower OT and AVP cytoplasmic mRNA levels than their nonlactating cohorts. We further compared OT and AVP cytoplasmic mRNAs in the hypothalamus of day 12 lactating rats that had been ovariectomized or sham ovariectomized on day 3 of lactation. Ovariectomized day 12 lactating animals had significantly lower OT and AVP cytoplasmic mRNA levels than their intact cohorts. These data refute the hypothesis that lactation is characterized by persistently elevated hypothalamic cytoplasmic OT and AVP mRNAs produced as a result of continuous stimulation by suckling and suggest that ovarian steroids may exert a modulatory effect on hypothalamic OT and AVP expression during early lactation. C1 UNIV PITTSBURGH,SCH MED,DEPT MED,DIV ENDOCRINOL & METAB,E1140 BIOMED SCI TOWER,PITTSBURGH,PA 15261. NIMH,NEUROPHYSIOL LAB,POOLESVILLE,MD 20837. FU NIDDK NIH HHS [5T32-DK-0752-18] NR 24 TC 56 Z9 56 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1993 VL 133 IS 6 BP 2704 EP 2710 DI 10.1210/en.133.6.2704 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MK151 UT WOS:A1993MK15100042 PM 7612074 ER PT J AU USDIN, TB MEZEY, E BUTTON, DC BROWNSTEIN, MJ BONNER, TI AF USDIN, TB MEZEY, E BUTTON, DC BROWNSTEIN, MJ BONNER, TI TI GASTRIC-INHIBITORY POLYPEPTIDE RECEPTOR, A MEMBER OF THE SECRETIN-VASOACTIVE INTESTINAL PEPTIDE RECEPTOR FAMILY, IS WIDELY DISTRIBUTED IN PERIPHERAL ORGANS AND THE BRAIN SO ENDOCRINOLOGY LA English DT Article ID PANCREATIC BETA-CELLS; SOMATOSTATIN-LIKE IMMUNOREACTIVITY; GLUCAGON-LIKE PEPTIDE-1; CALCITONIN RECEPTOR; RAT-BRAIN; HYBRIDIZATION HISTOCHEMISTRY; EXPRESSION CLONING; MOLECULAR-CLONING; CUSHINGS-SYNDROME; GLP-1 7-36AMIDE AB Gastric inhibitory polypeptide (GIP), or glucose-dependent insulinotropic peptide, is released from endocrine cells in the small intestine after meals. It is involved in several facets of the anabolic response and is thought to be particularly important in stimulating insulin secretion. We have cloned, functionally expressed, and mapped the distribution of the receptor for GIP. It is a member of the secretin-vasoactive intestinal polypeptide family of G-protein-coupled receptors. When expressed in tissue culture cells, it stimulates cAMP production (EC50 0.3 nm) and also increases intracellular calcium accumulation. GIP receptor mRNA is present in the pancreas as well as the gut, adipose tissue, heart, pituitary, and inner layers of the adrenal cortex, whereas it is not found in kidney, spleen, or liver. It is also expressed in several brain regions, including the cerebral cortex, hippocampus, and olfactory bulb. These results suggest that GIP may have previously undescribed actions. GIP receptor localization in the adrenal cortex suggests that it may have effects on glucocorticoid metabolism. Neither GIP nor its effects have been described in the central nervous system, and mRNA for the known peptide ligand for the receptor cannot be detected in the brain by in situ hybridization or polymerase chain reaction. This suggests that a novel peptide may be present in the brain. C1 NINCDS, CLIN NEUROSCI BRANCH, BETHESDA, MD 20892 USA. RP USDIN, TB (reprint author), NIMH, CELL BIOL LAB, BLDG 36, ROOM 3A17, BETHESDA, MD 20892 USA. RI Brownstein, Michael/B-8609-2009 NR 55 TC 321 Z9 327 U1 1 U2 9 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 DEC PY 1993 VL 133 IS 6 BP 2861 EP 2870 DI 10.1210/en.133.6.2861 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MK151 UT WOS:A1993MK15100066 PM 8243312 ER PT J AU ROFF, CF STRAUSS, JF GOLDIN, E JAFFE, H PATTERSON, MC AGRITELLIS, GC HIBBS, AM GARFIELD, M BRADY, RO PENTCHEV, PG AF ROFF, CF STRAUSS, JF GOLDIN, E JAFFE, H PATTERSON, MC AGRITELLIS, GC HIBBS, AM GARFIELD, M BRADY, RO PENTCHEV, PG TI THE MURINE NIEMANN-PICK TYPE-C LESION AFFECTS TESTOSTERONE PRODUCTION SO ENDOCRINOLOGY LA English DT Article ID LIPOPROTEIN-DERIVED CHOLESTEROL; LYSOSOMAL STORAGE DISORDER; HUMAN PLACENTAL TISSUE; MACROPHAGE FOAM CELLS; MOUSE LEYDIG-CELLS; POLYVINYLIDENE DIFLUORIDE; CULTURED FIBROBLASTS; HORMONAL-REGULATION; SEQUENCE-ANALYSIS; BALB/C MICE AB We have determined the effects of the Niemann-Pick type C (NPC) lesion, which impairs transport of cholesterol from lysosomes, on the androgenic status of male NPC mice. The mice have low serum testosterone levels resulting from decreased testosterone secretion. Testosterone secretion is reduced in NPC mouse testes incubated with 8-bromo-cAMP, 20alpha-hydroxycholesterol, and pregnenolone compared to testosterone release by normal mouse testes under identical conditions. Ultrastuctural examination of testes revealed a paucity of lipid droplets, extensive accumulation of inclusion bodies, and distorted endoplasmic reticulum in Leydig cells of adult NPC mice. The hypoandrogenemia caused systemic deficiencies in NPC mice. Seminal vesicles, a testosterone-responsive tissue, were underdeveloped in NPC male mice. The testosterone-responsive kidney beta-glucuronidase activity was also underexpressed. Seminal vesicle mass and beta-glucuronidase activity were increased by testosterone treatment of NPC mice. Many hepatic proteins, identified by microsequencing, were also deficient in NPC male mice. Levels of alpha2-mu-globulin, glutathione S-transferase-pi, carbonic anhydrase-III, and selenium-binding protein increased in normal male mice during puberty, but did not increase in the NPC male mice. Based on the increases in protein expression during puberty, differential expression in males and females, and the reported involvement of androgens in regulating expression of some of these proteins, deficient expression of most of these proteins in male NPC mice appears to result from low testosterone levels. We conclude that a defect in testicular testosterone production in NPC male mice causes a pleiotropic deficiency in androgen-sensitive expression of proteins in various organs. C1 NINCDS,NEUROCHEM LAB,BETHESDA,MD 20892. NIAID,BIOL RESOURCE BRANCH,BETHESDA,MD 20892. UNIV PENN,SCH MED,DEPT OBSTET & GYNECOL,PHILADELPHIA,PA 19104. RP ROFF, CF (reprint author), NINCDS,DEV & METAB NEUROL BRANCH,BLDG 10,ROOM 3D-12,BETHESDA,MD 20892, USA. OI Patterson, Marc/0000-0002-1116-126X FU NICHD NIH HHS [HD-06274]; NIDDK NIH HHS [DK-19525] NR 50 TC 32 Z9 33 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1993 VL 133 IS 6 BP 2913 EP 2923 DI 10.1210/en.133.6.2913 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MK151 UT WOS:A1993MK15100073 PM 8243319 ER PT J AU FRIEDMAN, TC CHEN, HC LOH, YP AF FRIEDMAN, TC CHEN, HC LOH, YP TI GENERATION OF 1-37 AND 1-38 FORMS OF ADRENOCORTICOTROPIN BY MONOPEPTIDYL AND DIPEPTIDYL SERINE CARBOXYPEPTIDASE ACTIVITIES IN BOVINE PITUITARY SECRETORY VESICLES SO ENDOCRINOLOGY LA English DT Article ID BETA-CELL-TROPIN; PRO-OPIOMELANOCORTIN; HORMONE BIOSYNTHESIS; INTERMEDIATE LOBE; DEGRADING ENZYME; RAT-BRAIN; PEPTIDES; PROTEOLYSIS; ENDORPHIN; PROTEIN AB ACTH is a 39-amino acid peptide synthesized in the pituitary as part of the precursor molecule, POMC. Analysis of bovine anterior pituitary homogenates and secretory vesicles revealed that in addition to ACTH-(1-39), ACTH-(1-37) and ACTH-(1-38) were also present in the lobe, indicating that carboxyl-terminal processing of ACTH-(1-39) occurred in vivo. Mono- and dipeptidyl carboxypeptidase activities that cleaved ACTH-(1-39) were detected in bovine intermediate and anterior pituitary secretory vesicle membranes and characterized. The dipeptidyl carboxypeptidase activity liberated ACTH-(1-37) and the dipeptide, Glu-Phe, and the monocarboxypeptidase activity generated, to a smaller extent, ACTH-(1-38) and phenylalanine from ACTH-(1-39). Kinetic studies indicated that the formation of ACTH-(1-37) occurred within minutes, whereas the formation of ACTH-(1-38) occurred within hours. Both enzymatic activities had a pH optimum of 5.5 and a K(m) of 14-18 mum for ACTH-(1-39), and were inhibited by serine and some thiol, but not metallo- or aspartic protease inhibitors. These unique serine carboxypeptidase(s) may function as a converting enzyme in vivo. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. RP FRIEDMAN, TC (reprint author), NICHHD,DEV NEUROBIOL LAB,CELLULAR NEUROBIOL SECT,BLDG 49,ROOM 5A-38,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 45 TC 5 Z9 5 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1993 VL 133 IS 6 BP 2951 EP 2961 DI 10.1210/en.133.6.2951 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MK151 UT WOS:A1993MK15100077 PM 8243323 ER PT J AU TINAJERO, JC FABBRI, A CIOCCA, DR DUFAU, ML AF TINAJERO, JC FABBRI, A CIOCCA, DR DUFAU, ML TI SEROTONIN SECRETION FROM RAT LEYDIG-CELLS SO ENDOCRINOLOGY LA English DT Note ID CORTICOTROPIN-RELEASING FACTOR; TESTIS; 5-HYDROXYTRYPTAMINE; GONADOTROPIN; PROTEIN AB In rat Leydig cells, serotonin (5HT) binds to 5HT2 receptors and stimulates the secretion of CRF which in turn acts as an inhibitor of gonadotropin-induced cAMP formation and androgen production. In the present study we defined the regulation of 5HT secretion in cultured Leydig cells. Adult Leydig cells secreted considerable quantities of 5HT (100-150 pg/10(6) cells per 10 min). The release of 5HT was acutely stimulated by hCG (ED50, 1.1 pM) with maximal stimulation at 10 pM hCG (160%). Forskolin also increased (+220%) 5HT release from cultures (ED50, 50 nM) while TPA was much less effective (+20%), indicating a major role for cAMP in gonadotropin-induced 5HT release. This was confirmed by the finding that 8-Br cAMP (1 mM) was an effective stimulus of 5HT release (+360%). Similar increases of 5HT release by hCG were observed in the absence of extracellular Ca2+. However, ionomycin was a potent stimulus of 5HT release, indicating that elevation of cytoplasmic [Ca2+] could also induce amine secretion. The 5HT content of Leydig cells ranged from 300 to 350 pg/10(6) cells, and decreased during stimulation of 5HT release. Also, immunohistochemical studies revealed specific staining of 5 HT in interstitial cells of the adult rat testis. These studies demonstrated that rat Leydig cells contain and secrete 5HT, and that 5HT release is stimulated by gonadotropin acting primarily through a cAMP-mediated mechanism. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,MOLEC ENDOCRINOL SECT,BLDG 49 6A-36,BETHESDA,MD 20892. NR 17 TC 25 Z9 26 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1993 VL 133 IS 6 BP 3026 EP 3029 DI 10.1210/en.133.6.3026 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MK151 UT WOS:A1993MK15100085 PM 8243331 ER PT J AU CESNJAJ, M KRSMANOVIC, LZ CATT, KJ STOJILKOVIC, SS AF CESNJAJ, M KRSMANOVIC, LZ CATT, KJ STOJILKOVIC, SS TI AUTOCRINE INDUCTION OF C-FOS EXPRESSION IN GT1 NEURONAL CELLS BY GONADOTROPIN-RELEASING-HORMONE SO ENDOCRINOLOGY LA English DT Note ID LUTEINIZING-HORMONE; HYPOTHALAMIC NEURONS; PROESTROUS SURGE; PROTEIN; SECRETION; ACTIVATION AB Activation of GnRH receptors in GnRH neuronal (GT1-7) cells causes marked and transient increases in c-fos expression, with peak response at 30 min. GnRH and des-Gly10-[D-Ala6]GnRH N-ethylamide induced concentration-dependent c-fos responses with EC50s of approximately 0.1 and approximately 1 nM, respectively. GnRH action was mimicked by phorbol 12-myristate-13-acetate (PMA), but stimulation of Ca2+ entry by K+-induced depolarization and Bay K 8644 was much less effective. In protein kinase C-depleted cells, the c-fos response to GnRH was reduced to that elicited by increased Ca2+ entry, and the effect of PMA was abolished. Thus, GnRH-induced c-fos expression in GT1 cells appears to be mediated predominantly by protein kinase C, and to a lesser extent by Ca2+. These findings demonstrate that c-fos expression can be induced in a peptidergic neuron by activation of receptors for its neurosecretory product. It is possible that the expression of c-fos in GnRH hypothalamic neurons during the proestrous surge of gonadotropins could likewise be stimulated by a positive feedback action of GnRH on its neuronal receptors. RP CESNJAJ, M (reprint author), NICHHD,ERRB,BLDG 49,ROOM 6A-36,BETHESDA,MD 20892, USA. NR 24 TC 38 Z9 38 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1993 VL 133 IS 6 BP 3042 EP 3045 DI 10.1210/en.133.6.3042 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MK151 UT WOS:A1993MK15100089 PM 8243334 ER PT J AU MELNICK, RL HUFF, J BARRETT, JC MARONPOT, RR LUCIER, G PORTIER, CJ AF MELNICK, RL HUFF, J BARRETT, JC MARONPOT, RR LUCIER, G PORTIER, CJ TI CELL-PROLIFERATION AND CHEMICAL CARCINOGENESIS - SYMPOSIUM OVERVIEW SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material AB Cancer, by definition, is a proliferative disease. The fundamental scientific issue explored at the international symposium ''Cell Proliferation and Chemical Carcinogenesis'' was the impact of chemically enhanced cell proliferation on the dynamic carcinogenic processes. This conference, held at the National Institute of Environmental Health Sciences January 14-16, 1992, provided an open forum for the exchange of new results, information, and ideas in four areas: a) general principles of cell division and carcinogenesis, b) critical evaluation of cell proliferation methodologies, c) cell proliferation and modeling of organ-specific carcinogenesis, and d) cell proliferation and human carcinogenesis. This overview summarizes key findings from that symposium. The general view expressed was that although cell proliferation is involved inextricably in the development of cancers, chemically enhanced cell division does not reliably predict carcinogenicity. Our knowledge of the multistep nature of carcinogenesis has advanced substantially during recent years; however, much still needs to be learned. A greater understanding of the cellular and molecular events in chemical carcinogenesis should improve all aspects of the overall risk assessment process, including extrapolations based on dose, species, and interindividual differences. RP MELNICK, RL (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 33 TC 25 Z9 25 U1 0 U2 1 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1993 VL 101 SU 5 BP 3 EP 7 DI 10.2307/3431836 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA NB891 UT WOS:A1993NB89100001 PM 7912189 ER PT J AU AFSHARI, CA BARRETT, JC AF AFSHARI, CA BARRETT, JC TI CELL CYCLE CONTROLS - POTENTIAL TARGETS FOR CHEMICAL CARCINOGENS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Symposium on Cell Proliferation and Chemical Carcinogenesis CY JAN 14-16, 1992 CL RESEARCH TRIANGLE PARK, NC ID MAMMALIAN-CELL-CYCLE; P34CDC2 PROTEIN-KINASE; WILD-TYPE P53; FISSION YEAST; TYROSINE PHOSPHORYLATION; HUMAN CDC2; S-PHASE; DNA-REPLICATION; SACCHAROMYCES-CEREVISIAE; RETINOBLASTOMA PROTEIN AB The progression of the cell cycle is controlled by the action of both positive and negative growth regulators. The key players in this activity include a family of cyclins and cyclin-dependent kinases, which are themselves regulated by other kinases and phosphatases. Maintenance of balanced cell cycle controls may be directly linked to genomic stability. Loss of the checkpoints involved in cell cycle control may result in unrepaired DNA damage during DNA synthesis or mitosis leading to genetic mutations and contributing to carcinogenesis. C1 NIEHS,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,CHAPEL HILL,NC. NR 91 TC 18 Z9 18 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1993 VL 101 SU 5 BP 9 EP 14 DI 10.2307/3431837 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA NB891 UT WOS:A1993NB89100002 PM 8013430 ER PT J AU HUFF, J AF HUFF, J TI ABSENCE OF MORPHOLOGIC CORRELATION BETWEEN CHEMICAL TOXICITY AND CHEMICAL CARCINOGENESIS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Symposium on Cell Proliferation and Chemical Carcinogenesis CY JAN 14-16, 1992 CL RESEARCH TRIANGLE PARK, NC ID NATIONAL TOXICOLOGY PROGRAM; LONG-TERM CARCINOGENICITY; CELL-PROLIFERATION; 1,3-BUTADIENE; MITOGENESIS; MECHANISMS; NEOPLASIA; EXPOSURE; RODENTS; RISKS AB The experimental data set used to evaluate site-specific histopathologic correspondence between the morphologic end points of toxicity and carcinogenicity comprises 130 chemical carcinogenesis studies. Nearly 1500 sex-species-exposure-group experiments were evaluated for a) evidence of toxicity or/and carcinogenicity, b) dose-response relationships, c) site-specific correlations of toxicity and carcinogenicity, and d) correspondence with Salmonella mutagenicity. The major conclusions are that chemicals evaluated for long-term toxicity and carcinogenicity in experimental animals divide typically and consistently into three categories: a) chemicals causing organ toxicity without cancer, b) chemicals causing site-specific cancer with no associated toxicity, and c) chemicals causing both toxicity and cancer in the same organ. Few chemicals overall (and none in this data set) fit the remaining group that cause neither toxicity nor carcinogenicity under these protocol conditions. Mutagenicity exhibited no consistent pattern with any of these groupings. Only 7 of 53 ''positive'' chemicals had target organ toxicity at all sites of carcinogenicity. Just three chemicals showed carcinogenic effects at the highest exposure concentrations without supporting evidence of tumors at the lower levels. From these comparative morphological analyses, and for almost all cases, available data do not support a correlation between chemically induced toxicity or regenerative phenomena and carcinogenicity. Consequently, until scientific knowledge about molecular mechanisms of chemical carcinogenesis becomes better understood and generally accepted, attempts to use toxicity findings to modify risk assessment processes will be fraught with uncertainty and thus could have a negative impact on public health. RP HUFF, J (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 80 TC 28 Z9 28 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1993 VL 101 SU 5 BP 45 EP 53 DI 10.2307/3431841 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA NB891 UT WOS:A1993NB89100006 PM 8013424 ER PT J AU GOLDSWORTHY, TL BUTTERWORTH, BE MARONPOT, RR AF GOLDSWORTHY, TL BUTTERWORTH, BE MARONPOT, RR TI CONCEPTS, LABELING PROCEDURES, AND DESIGN OF CELL-PROLIFERATION STUDIES RELATING TO CARCINOGENESIS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Symposium on Cell Proliferation and Chemical Carcinogenesis CY JAN 14-16, 1992 CL RESEARCH TRIANGLE PARK, NC ID NUCLEAR ANTIGEN; LIVER; EXPRESSION; WY-14,643; MICE; RATS AB Chemicals may induce cell proliferation directly as mitogens or indirectly via cell death with subsequent proliferation to replace lost cells. Chemically induced proliferation has been demonstrated to play a role in the carcinogenic process. A wide range of procedures and techniques are currently being used to define the quantitative relationship between the extent and duration of chemically induced cell proliferation and carcinogenic potential in different species and target organs. However, a limited database and nonstandard protocols and procedures for measuring cell proliferation have made it difficult to compare results between laboratories. Comparison of frequencies of S phase between control and treated animals is the most commonly used end point in cell proliferation studies and may be regarded as an indirect indication of a proliferative response. This response can be ascertained as labeling indexes (LI; percentage of cells in S phase) after the administration of the DNA precursor labels (tritiated thymidine; H-3-TdR; bromodeoxyuridine, BrdU) or through immunostaining of the endogenous cell replication marker, proliferating cell nuclear antigen (PCNA). Both approaches are applicable to tissue sections. An important issue in the design of experimental studies for measuring LI is determining how and when to investigate proliferative responses in relation to the chemical treatment regimen. Variables to consider when designing cell proliferation studies include the animal's age, chemical dose and method of treatment, choice and dose of label, time and length that the label is administered, and methods of quantitation. Study design considerations depend on the experimental objective. A common approach to characterize the complex relationship of cell proliferation and carcinogenic activity has been to focus on relatively early (less than 90 days) proliferative responses in the target tissue. However, a larger database on the duration and nature of the chemically induced proliferative response under bioassay conditions in the target cell population is required to more clearly establish the role of this end point in the cancer process. in addition, studies must also investigate mitogenic versus cytotoxic induction of cell proliferation in normal and preneoplastic cells and differential toxicity that may provide a preferential growth advantage to spontaneous or chemically induced intermediate or malignant cells. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP GOLDSWORTHY, TL (reprint author), CHEM IND INST TOXICOL,POB 12137,RES TRIANGLE PK,NC 27709, USA. NR 31 TC 45 Z9 46 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1993 VL 101 SU 5 BP 59 EP 65 DI 10.2307/3431843 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA NB891 UT WOS:A1993NB89100008 PM 7912190 ER PT J AU PORTIER, CJ KOPPSCHNEIDER, A SHERMAN, CD AF PORTIER, CJ KOPPSCHNEIDER, A SHERMAN, CD TI USING CELL REPLICATION DATA IN MATHEMATICAL-MODELING IN CARCINOGENESIS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Symposium on Cell Proliferation and Chemical Carcinogenesis CY JAN 14-16, 1992 CL RESEARCH TRIANGLE PARK, NC ID HISTORICAL CONTROL ANIMALS; MULTISTAGE MODELS; 2-STAGE MODELS; TUMOR ONSET; DNA DAMAGE; CANCER; DESIGN; REPAIR; GENES; RAS AB Risk estimation involves the application of quantitative models of dose versus response to carcinogenicity data. Recent advances in biology, computing, and mathematics have led to the application of mathematically complicated, mechanistically based models of carcinogenesis to the estimation of risks. This paper focuses on two aspects of this application, distinguishing between models using available data and the development of new models to keep pace with research developments. C1 DEUTSCH KREBSFORSCHUNGSZENTRUM,BIOSTAT ABT,W-6900 HEIDELBERG 1,GERMANY. UNIV WATERLOO,DEPT MATH & ACTUARIAL SCI,WATERLOO N2L 3G1,ON,CANADA. RP PORTIER, CJ (reprint author), NIEHS,STAT & BIOMATH BRANCH,RISK METHODOL SECT,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 35 TC 10 Z9 10 U1 1 U2 2 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1993 VL 101 SU 5 BP 79 EP 86 DI 10.2307/3431846 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA NB891 UT WOS:A1993NB89100011 PM 8013428 ER PT J AU COHEN, SM ELLWEIN, LB AF COHEN, SM ELLWEIN, LB TI USE OF CELL-PROLIFERATION DATA IN MODELING URINARY-BLADDER CARCINOGENESIS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Symposium on Cell Proliferation and Chemical Carcinogenesis CY JAN 14-16, 1992 CL RESEARCH TRIANGLE PARK, NC ID SODIUM SACCHARIN; N-<4-(5-NITRO-2-FURYL)-2-THIAZOLYL>FORMAMIDE; RAT AB A multistage, probabilistic, biologically based model of carcinogenesis has been developed involving qualitative and quantitative aspects of the process. A chemical can affect the risk of cancer by directly damaging DNA and/or increasing the number of cell divisions during which errors in DNA replication can occur. Based on this model, carcinogens are classified as genotoxic versus nongenotoxic; nongenotoxic chemicals are further divided on the basis of whether or not they act through a specific cell receptor. Nongenotoxic compounds, particularly those acting through a nonreceptor mechanism, are likely to have dose and/or species-specific thresholds. This classification also implies the existence of chemicals that will be carcinogenic at high doses in animal models, but because of dose and/or mechanistic considerations, will not be carcinogenic to humans at levels of exposure. N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) and 2-acetylaminofluorene (AAF) are classical genotoxic bladder carcinogens that also cause proliferative effects at higher doses. Although there is an apparent no-effect level for the urinary bladder carcinogenicity of these two compounds at low doses, in reality, DNA adducts form at these low levels, and it is likely that there is a cancer effect (no threshold), but it is below the level of detection of the bioassay. These conclusions are based on studies involving multiple doses and time points in rodents, including results from the ED(01). Pellets implanted directly into the rodent bladder lumen or calculi formed in the urine as a result of an administered chemical cause abrasion of the urothelium, and a marked increase in cell proliferation and cell number, and ultimately tumors. A threshold is readily definable based on physiologic, chemical, and pharmacokinetic considerations. Sodium saccharin also produces bladder cancer at high doses in rats, particularly males, if it is administered beginning at birth or earlier. The mechanism appears to be related to the formation of a silicate precipitate and/or crystals formed in the rat urine, which act as abrasives or cytotoxic materials, leading to increased cell proliferation and ultimately tumors. Numerous other sodium salts have similar effects. This effect is not observed in the mouse, hamster, or monkey, and epidemiological evidence suggests that it does not occur in humans. Thus, for sodium saccharin, even in the susceptible species, the rat, there appears to be a dose threshold, and extrapolation to humans appears inappropriate based on mechanistic considerations. C1 EPPLEY INST CANC RES,OMAHA,NE 68198. NEI,BETHESDA,MD 20892. RP COHEN, SM (reprint author), UNIV NEBRASKA,MED CTR,DEPT PATHOL & MICROBIOL,600 S 42ND ST,OMAHA,NE 68198, USA. FU NCI NIH HHS [CA32315, CA36727] NR 15 TC 15 Z9 15 U1 0 U2 1 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1993 VL 101 SU 5 BP 111 EP 113 DI 10.2307/3431852 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA NB891 UT WOS:A1993NB89100017 PM 8013397 ER PT J AU MCLAUGHLIN, JK AF MCLAUGHLIN, JK TI RENAL-CELL CANCER AND EXPOSURE TO GASOLINE - A REVIEW SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT International Symposium on the Health Effects of Gasoline CY NOV 05-08, 1991 CL MIAMI, FL SP AMER PETR INST, ASSOC SWEDISH AUTOMOBILE MANUFACTURERS & WHOLESALERS, HLTH EFFECTS INST, INST EVALUAT HLTH RISKS, INST PETR, JAPAN AUTOMOBILE MANUFACTURERS ASSOC, MOTOR VEHICLE MANUFACTURERS ASSOC US, PETR ASSOC JAPAN, US EPA, W STATES PETR ASSOC ID DRY CLEANING WORKERS; RETROSPECTIVE COHORT MORTALITY; RISK-FACTORS; URINARY-TRACT; KIDNEY CANCER; CARCINOMA; SMOKING; LAUNDRY; DEATH; EPIDEMIOLOGY AB A review of the epidemiology of renal cell cancer is presented. Risk factors for renal cell cancer such as cigarette smoking, obesity, diet, and use of analgesics and prescription diuretics are examined. Although uncommon, occupational risk factor's are also reviewed. Studies examining gasoline exposure and renal cell cancer are evaluated, including investigations recently presented at a meeting on this topic. Overall, most studies find no link between gasoline exposure and renal cell cancer; moreover, the experimental evidence that initiated the health concern is no longer considered relevant to humans. Positive associations, however, reported in two recent studies prevent a firm conclusion of no risk for this exposure. RP MCLAUGHLIN, JK (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTST PROGRAM,6130 EXECUT BLVD,EPN-415,ROCKVILLE,MD 20852, USA. NR 47 TC 19 Z9 19 U1 0 U2 1 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1993 VL 101 SU 6 BP 111 EP 114 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA MY181 UT WOS:A1993MY18100016 PM 8020434 ER PT J AU WARD, JM UNO, H KURATA, Y WEGHORST, CM JANG, JJ AF WARD, JM UNO, H KURATA, Y WEGHORST, CM JANG, JJ TI CELL-PROLIFERATION NOT ASSOCIATED WITH CARCINOGENESIS IN RODENTS AND HUMANS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Symposium on Cell Proliferation and Chemical Carcinogenesis CY JAN 14-16, 1992 CL RESEARCH TRIANGLE PARK, NC ID URINARY-BLADDER CARCINOGENESIS; MALE B6C3F1 MICE; F344 RATS; DI(2-ETHYLHEXYL) PHTHALATE; BUTYLATED HYDROXYANISOLE; DNA-SYNTHESIS; NASAL CAVITY; PROMOTING ACTIVITIES; TUMOR PROMOTION; CANCER AB Cell proliferation has often been found to be associated with carcinogenesis in rodents and humans at different stages of the multistage carcinogenesis process. The multistage process includes initiation, promotion, and progression phases. At each phase, increasing the normal level of cell turnover of target cells may enhance carcinogenesis. However, we present evidence that normal levels of cell turnover, or increasing the rate of cell turnover at these different stages, do not necessarily lead to enhanced carcinogenesis. In normal tissues, the length of the cell cycle depends on the age of the host and varies from tissue to tissue. Tissues with normal short cell cycles, such as intestine and bone marrow, do not show a high rate of spontaneous tumors in most species. Cells with higher turnover should be more susceptible to carcinogens at the initiation stage of carcinogenesis if cell proliferation per se causes cancer and if these cells or their progeny survive. Cancer in humans is more often associated with specific etiological factors rather than with the natural proliferative rate of specific tissues. For many tissues of humans and rodents, age-related diseases develop in a progressive, irreversible manner. Often, naturally occurring chronic degenerative and inflammatory changes in a tissue (e.g., kidney, liver, heart, reproductive tract) lead to chronic regeneration of the damaged tissue. Yet, cancer is rarely found in these tissues. In rodent carcinogenesis experiments, chronic toxic lesions, accompanied by increases in normal levels of cell turnover, have sometimes been observed in target organs of nongenotoxic carcinogens. More often, however, organ-specific nongenotoxic toxins are not carcinogens. These toxins include compounds toxic for the liver, kidney, and nasal cavity. In 19 inhalation bioassays conducted by the National Toxicology Program, 5/5 nasal carcinogens and 12/14 nasal noncarcinogens caused nasal lesions usually associated with chronic cell proliferation. Although cell proliferation may contribute to multistage carcinogenesis, cell proliferation is not necessarily a tumor promoter or cocarcinogen. C1 NCI,OFF LAB ANIM SCI,VET & TUMOR PATHOL SECT,FREDERICK,MD 21702. TEIJIN LTD,TOKYO,JAPAN. NAGOYA CITY UNIV,SCH MED,NAGOYA,JAPAN. KOREA CANC CTR HOSP,SEOUL,SOUTH KOREA. RP WARD, JM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,TUMOR PATHOL & PATHOGENESIS SECT,FREDERICK,MD 21702, USA. NR 70 TC 53 Z9 54 U1 1 U2 1 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1993 VL 101 SU 5 BP 125 EP 135 DI 10.2307/3431855 PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA NB891 UT WOS:A1993NB89100020 PM 8013399 ER PT J AU FOLEY, J TON, T MARONPOT, R BUTTERWORTH, B GOLDSWORTHY, TL AF FOLEY, J TON, T MARONPOT, R BUTTERWORTH, B GOLDSWORTHY, TL TI COMPARISON OF PROLIFERATING CELL NUCLEAR ANTIGEN TO TRITIATED-THYMIDINE AS A MARKER OF PROLIFERATING HEPATOCYTES IN RATS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Symposium on Cell Proliferation and Chemical Carcinogenesis CY JAN 14-16, 1992 CL RESEARCH TRIANGLE PARK, NC ID DNA POLYMERASE-DELTA; PCNA CYCLIN; MONOCLONAL-ANTIBODY; AUXILIARY PROTEIN; TISSUES; EXPRESSION; LINES AB Proliferating cell nuclear antigen (PCNA), an endogenous nuclear protein, has recently been used to identify replicating cells. PCNA was compared to tritiated thymidine ([H-3].TdR), a reliable and accurate exogenous labeling agent, to ascertain if PCNA gives comparable results for quantitative cell proliferation. Male F344 rats were treated with a single dose of 500 mg/kg 4-acetylaminofluorene (4-AAF), a known liver mitogen. Rats (n = 5) were euthanized and necropsied at 6, 12, 18, 24, 36, 48, 96, or 192 hr after treatment. Two hours before necropsy, rats were pulse-dosed with [H-3]-TdR (2 mCi/kg body weight). Livers were sectioned, autoradiography performed, and labeling indexes (LI), a measurement of the percentage of S-phase hepatocytes, determined. One and a half years after the completion of this study, the archival paraffin blocks of the liver tissue were sectioned and stained for PCNA by an immunohistochemical procedure. Immunocytochemical staining patterns of proliferating cell nuclear antigen expression permitted the recognition of G(1), S, G(2),escent cells. PCNA LI, generated by scoring only cells exhibiting S-phase staining patterns, was compared to the pulse [H-3]-TdR LI for each animal. Similar periportal staining patterns of S-phase nuclei were detected by both markers. The [H-3]-TdR LI and the PCNA LI exhibited a peak at 24 hr of approximately the same magnitude. However, while the [H-3]-TdR LI had returned to near baseline at the 48-hr time point, the PCNA LI remained elevated until the 96-hr time point. This sustained elevation of the PCNA index cannot be explained at this time. Examination of all other time points revealed similar S-phase LI by either method. PCNA immunostaining allowed for the estimation of the growth fraction. A time-dependent alteration in the hepatic growth fraction curve was a consequence of 4-AAF treatment. C1 CHEM IND INST TOXICOL,RES TRIANGLE PK,NC 27709. RP FOLEY, J (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Foley, Julie/0000-0001-9726-2821 NR 30 TC 88 Z9 89 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1993 VL 101 SU 5 BP 199 EP 205 DI 10.2307/3431868 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA NB891 UT WOS:A1993NB89100033 PM 7912186 ER PT J AU SIVAK, A MCCLELLAN, R ROMBOUT, P MCLAUGHLIN, J ENTERLINE, P INFANTE, P AF SIVAK, A MCCLELLAN, R ROMBOUT, P MCLAUGHLIN, J ENTERLINE, P INFANTE, P TI SYMPOSIUM ON THE HEALTH-EFFECTS OF GASOLINE - PANEL DISCUSSION ON THE STATE OF THE SCIENCE SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 CHEM IND INST TOXICOL,RES TRIANGLE PK,NC 27709. NATL INST PUBL HLTH & ENVIRONM PROTECT,3720 BA BILTHOVEN,NETHERLANDS. NCI,BETHESDA,MD 20892. US OCCUPAT SAFETY & HLTH ADM,WASHINGTON,DC. HLTH EFFECTS INST,CAMBRIDGE,MA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1993 VL 101 SU 6 BP 201 EP 202 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA MY181 UT WOS:A1993MY18100024 PM 8020443 ER PT J AU GREENWELL, A FOLEY, JF MARONPOT, RR AF GREENWELL, A FOLEY, JF MARONPOT, RR TI DETECTING PROLIFERATING CELL NUCLEAR ANTIGEN IN ARCHIVAL RODENT TISSUES SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Symposium on Cell Proliferation and Chemical Carcinogenesis CY JAN 14-16, 1992 CL RESEARCH TRIANGLE PARK, NC ID DNA POLYMERASE-DELTA; CYCLIN PCNA; ENHANCEMENT METHOD; AUXILIARY PROTEIN; PARAFFIN SECTIONS; EMBEDDED TISSUES; CARCINOGENESIS; MITOGENESIS; EXPRESSION; INDEX AB The detection of proliferating cell nuclear antigen (PCNA), an endogenous cell replication marker, has lacked sensitivity in paraffin-embedded archival tissues fixed in formalin. An enhanced immunohistochemical procedure to detect PCNA has been successfully applied to rat and mouse tissues. Tissue sections are heated in a microwave oven in the presence of an antigen-retrieval solution of heavy-metal salts. Positive immunostaining of S-phase cells, an indication of DNA replicative activity, has been consistently obtained in tissues fixed for more than 24 months in formalin and in paraffin blocks stored for up to 19 months. Use of this technique will allow retrospective staining of rodent tissues from previously conducted toxicity and carcinogenicity studies. RP GREENWELL, A (reprint author), NIEHS,NATL TOXICOL PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 16 TC 10 Z9 10 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1993 VL 101 SU 5 BP 207 EP 209 DI 10.2307/3431869 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA NB891 UT WOS:A1993NB89100034 PM 7912187 ER PT J AU CUNNINGHAM, ML ELWELL, MR MATTHEWS, HB AF CUNNINGHAM, ML ELWELL, MR MATTHEWS, HB TI SITE-SPECIFIC CELL-PROLIFERATION IN RENAL TUBULAR CELLS BY THE RENAL TUBULAR CARCINOGEN TRIS(2,3-DIBROMOPROPYL)PHOSPHATE SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Symposium on Cell Proliferation and Chemical Carcinogenesis CY JAN 14-16, 1992 CL RESEARCH TRIANGLE PARK, NC ID HEPATOCELLULAR PROLIFERATION; CHEMICAL CARCINOGENESIS; HEPATOCARCINOGENICITY; MUTAGENICITY; RATS; SALMONELLA; TOXICITY; RODENTS AB Our laboratory has been examining the mechanisms whereby chemicals are mutagenic in short-term in-vitro assays yet are not carcinogenic in a-year rodent bioassays. Previous studies indicated that mutagenic carcinogens increased the amount of cell turnover in the target organ, but that mutagenic noncarcinogens failed to do so. The present study compares the incidence of cell proliferation in specific regions of the kidney, which is the site of carcinogenicity, with cell proliferation induced in a nontarget tissue, the liver, by the mutagenic renal tubular carcinogen tris(2,3-dibromopropyl)phosphate (TRIS). Renal tubular adenocarcinoma induced by TRIS was the only tumor type identified in male F344 rats, and it was localized in the outer medulla. Male F344 rats were fed a diet containing 0, 50, or 100 ppm TRIS for 14 days. These doses were identical to the doses given in the National Toxicology Program cancer bioassay. Replicating cells were labeled with bromodeoxyuridine administered by an osmotic minipump and identified in tissue sections from liver and kidney using immunohistochemical techniques. Examination of liver sections showed no chemically related increases in cell proliferation above control for either dose group. However, in the kidney, TRIS induced significant cell proliferation that was localized in the renal outer medulla region, the target area for carcinogenesis. The labeling index (number of labeled cells/total number of cells counted) in the kidneys of TRIS-exposed rats was increased approximately 4-fold in the outer medulla and was not increased in the cortex or inner medulla. The results of this study suggest an association between the chemically-induced renal cell proliferation and the renal carcinogenicity of TRIS. RP CUNNINGHAM, ML (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 15 TC 14 Z9 14 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1993 VL 101 SU 5 BP 253 EP 257 DI 10.2307/3431877 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA NB891 UT WOS:A1993NB89100042 PM 8013416 ER PT J AU KANNO, J FOLEY, JF KARI, F ANDERSON, MW MARONPOT, RR AF KANNO, J FOLEY, JF KARI, F ANDERSON, MW MARONPOT, RR TI EFFECT OF METHYLENE-CHLORIDE INHALATION ON REPLICATIVE DNA-SYNTHESIS IN THE LUNGS OF FEMALE B6C3F(1) MICE SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Symposium on Cell Proliferation and Chemical Carcinogenesis CY JAN 14-16, 1992 CL RESEARCH TRIANGLE PARK, NC ID MOUSE LUNG; CELL-PROLIFERATION; PULMONARY TUMORS; DICHLOROMETHANE; CARCINOGENESIS; PROGRESSION; METABOLISM; LIVER AB In the National Toxicology Program a-year inhalation study of dichloromethane (DCM), there was a significant increase in pulmonary neoplasms in female B6C3F(1) mice exposed to 2000 ppm (overall rates of 30/48 versus 5/50 in control). Replicative DNA synthesis was examined to evaluate the potential role of treatment-induced lung cell proliferation on pulmonary carcinogenicity. Tritiated thymidine incorporation was assessed in methacrylate plastic sections after 1, 2, 3, or 4 weeks of inhalation exposure to 2000 ppm or 8000 ppm DCM. Similar measurements of labeling indexes were made after 13 and 26 weeks of exposure to 2000 ppm DCM using bromodeoxyuridine as the labeling agent. In all cases the labeling agent was delivered over a 6-day period using osmotic minipumps. The labeling index (LI) of bronchiolar epithelium (two branches proximal to the terminal bronchiole) of mice exposed to 2000 ppm DCM for 2-26 weeks decreased to 40-60% of the control. Terminal bronchioles showed a similar decrease in LI. Mice exposed to 8000 ppm DCM had a less dramatic decrease in LI. No pathological change was found in the exposed lungs. It is concluded that inhalation exposure to DCM for up to 26 weeks reduces cell turnover of bronchiolar cells in female B6C3F(1) mice. C1 NIEHS,RES TRIANGLE PK,NC 27709. TOKYO MED & DENT UNIV,FAC MED,DEPT PATHOL,TOKYO 113,JAPAN. NR 23 TC 10 Z9 10 U1 0 U2 2 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1993 VL 101 SU 5 BP 271 EP 276 DI 10.2307/3431880 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA NB891 UT WOS:A1993NB89100045 PM 8013420 ER PT J AU GHANAYEM, BI SANCHEZ, IM MARONPOT, RR ELWELL, MR MATTHEWS, HB AF GHANAYEM, BI SANCHEZ, IM MARONPOT, RR ELWELL, MR MATTHEWS, HB TI RELATIONSHIP BETWEEN THE TIME OF SUSTAINED ETHYL ACRYLATE FORESTOMACH HYPERPLASIA AND CARCINOGENICITY SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Symposium on Cell Proliferation and Chemical Carcinogenesis CY JAN 14-16, 1992 CL RESEARCH TRIANGLE PARK, NC ID INDUCED GASTRIC TOXICITY; FISCHER 344 RATS; URINARY-BLADDER; LESIONS AB Chronic administration of ethyl acrylate (EA) by gavage at 100 or 200 mg/kg/day resulted in a significant dose-dependent increase in the incidence of forestomach (FS) squamous cell papillomas and carcinomas in both sexes of F344 rats and B6C3F(1) mice. Subsequent work in this laboratory was designed to investigate the relationship between EA-induced FS hyperplasia and carcinogenicity. Current studies have focused on determining the time required for sustained FS hyperplasia to produce neoplastic transformation. Results of these studies demonstrated that gavage administration of EA to male F344 rats at 200 mg/kg/day for 6 or 12 months caused a sustained increase in FS epithelial hyperplasia for as long as exposure to EA continued. However, FS hyperplasia regressed, and no neoplasms developed when animals receiving EA for 6 months were allowed to recover until they were sacrificed at 24 months of age. In contrast, rats treated for 12 months and allowed 9 months recovery developed FS squamous cell carcinomas (3/13) and papillomas (1/13) for a combined incidence of 4/13. No gross lesions were detected in the liver of any of the rats treated with EA or corn oil vehicle, confirming the tissue specificity in the relationship between EA-induced FS hyperplasia and carcinogenesis. In conclusion, the present work has demonstrated that FS hyperplasia is selectively sustained at the site of EA-induced carcinogenicity for as long as EA is administered and has also demonstrated a temporal relationship between FS mucosal hyperplasia and the development of FS neoplasia by EA. It is speculated that whereas a temporal relationship probably exists between FS hyperplasia and tumor development for many chemicals known to increase cell proliferation, this relationship may vary significantly from one chemical to another and with the target tissue and may be influenced by the mutagenicity of chemicals. RP GHANAYEM, BI (reprint author), NIEHS,EXPTL TOXICOL BRANCH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 14 TC 4 Z9 4 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1993 VL 101 SU 5 BP 277 EP 279 DI 10.2307/3431881 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA NB891 UT WOS:A1993NB89100046 PM 8013421 ER PT J AU TAKAHASHI, K LINDAMOOD, C MARONPOT, RR AF TAKAHASHI, K LINDAMOOD, C MARONPOT, RR TI RETROSPECTIVE STUDY OF POSSIBLE ALPHA-2-MU-GLOBULIN NEPHROPATHY AND ASSOCIATED CELL-PROLIFERATION IN MALE FISCHER-344 RATS DOSED WITH T-BUTYL ALCOHOL SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Symposium on Cell Proliferation and Chemical Carcinogenesis CY JAN 14-16, 1992 CL RESEARCH TRIANGLE PARK, NC ID DNA POLYMERASE-DELTA; NUCLEAR ANTIGEN; AUXILIARY PROTEIN; CYCLIN PCNA; ALPHA-2U-GLOBULIN; REPLICATION; TOXICITY AB Tert-butyl alcohol, an important commodity chemical, additive to unleaded gasoline, and contaminant of drinking water, was evaluated for toxicity and was found to enhance nephropathy in male Fischer 344 rats. Because male rats treated with t-butyl alcohol for 2 years had a low incidence of renal cortical tumors, additional renal sections for the 90-day toxicity study were examined for the presence of hyaline droplet accumulation, nephropathy, and evidence of replicative DNA synthesis (S-phase nuclei) to indirectly and retrospectively investigate a possible role of alpha-2 mu-globulin in the pathogenesis of the nephropathy. Dose levels for t-butyl alcohol were 0, 0.25, 0.5, 1, 2, and 4% (w/v) administered in drinking water. Significant body weight gain depressions were observed in all treated males, and there was an absolute weight loss in the 4% male group, none of which survived to the end of the study. Except for the 4% dose group, there was a treatment-related increase in hyaline droplet accumulation in the renal proximal tubules with crystalline, rectangular, and rhomboid forms of the protein evident. The severity of nephropathy was enhanced in treated rats, except for the 4% dose group. Replicative DNA synthesis, as measured by immunohistochemical staining for proliferating cell nuclear antigen, was increased in proximal tubules of rats dosed with 2% t-butyl alcohol. It is concluded that t-butyl alcohol exacerbated nephropathy in male Fischer 344 rats and increased renal accumulation of hyaline protein material consistent with alpha-2 mu-globulin deposition. C1 NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. INST ENVIRONM TOXICOL,KODAIRA,TOKYO 187,JAPAN. SO RES INST,KETTERING MEYER LAB,BIRMINGHAM,AL 35225. NR 15 TC 22 Z9 22 U1 0 U2 1 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1993 VL 101 SU 5 BP 281 EP 285 DI 10.2307/3431882 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA NB891 UT WOS:A1993NB89100047 PM 7516874 ER PT J AU MARONPOT, RR FOLEY, JF TAKAHASHI, K GOLDSWORTHY, T CLARK, G TRITSCHER, A PORTIER, C LUCIER, G AF MARONPOT, RR FOLEY, JF TAKAHASHI, K GOLDSWORTHY, T CLARK, G TRITSCHER, A PORTIER, C LUCIER, G TI DOSE-RESPONSE FOR TCDD PROMOTION OF HEPATOCARCINOGENESIS IN RATS INITIATED WITH DEN - HISTOLOGIC, BIOCHEMICAL, AND CELL-PROLIFERATION END-POINTS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID EPIDERMAL GROWTH-FACTOR; ALTERED HEPATIC FOCI; TUMOR PROMOTION; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; LIVER; CARCINOGENESIS; DIETHYLNITROSAMINE; BINDING; MODEL; INCREASES C1 CHEM IND INST TOXICOL,RES TRIANGLE PK,NC 27709. RP MARONPOT, RR (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 42 TC 52 Z9 52 U1 1 U2 3 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1993 VL 101 IS 7 BP 634 EP 642 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA MQ713 UT WOS:A1993MQ71300016 PM 8143597 ER PT J AU DAMSTRA, T KUROKAWA, Y AF DAMSTRA, T KUROKAWA, Y TI THE 4TH UNITED-STATES-JAPAN MEETING ON THE TOXICOLOGICAL CHARACTERIZATION OF ENVIRONMENTAL CHEMICALS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material ID METABOLIC-ACTIVATION SYSTEM; EMBRYO TERATOGENESIS ASSAY; DEVELOPMENTAL TOXICITY; INVITRO; XENOPUS; GLUCOSE; TESTS; FISH C1 NATL INST HLTH SCI,BIOL SAFETY RES CTR,TOKYO,TOKYO,JAPAN. RP DAMSTRA, T (reprint author), NIEHS,POB 12233,MD A2-07,RES TRIANGLE PK,NC 27709, USA. NR 39 TC 1 Z9 1 U1 0 U2 1 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1993 VL 101 IS 7 BP 644 EP 649 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA MQ713 UT WOS:A1993MQ71300017 PM 8143598 ER PT J AU TAM, WWH ANDREASSON, KI LOH, YP AF TAM, WWH ANDREASSON, KI LOH, YP TI THE AMINO-TERMINAL SEQUENCE OF PROOPIOMELANOCORTIN DIRECTS INTRACELLULAR TARGETING TO THE REGULATED SECRETORY PATHWAY SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Article DE INTRACELLULAR TRANSPORT; ATT-20 CELLS; PROHORMONE; SECRETORY GRANULES ID ANTERIOR-PITUITARY CELLS; ADRENOCORTICOTROPIN SECRETION; ARGININE VASOPRESSIN; INTERMEDIATE LOBE; MESSENGER-RNA; GOLGI-COMPLEX; TUMOR-CELLS; ATT20 CELLS; TRANSPORT; PROTEINS AB The molecular signal which targets the pro-opiomelanocortin (POMC) prohormone into the regulated secretory pathway was investigated. DNA sequences encoding the first 10, 26, 50, and 101 N-terminal amino acids of mouse POMC were fused in frame to the chloramphenicol acetyltransferase (CAT) gene and expressed in AtT-20 cells. Immunofluorescence microscopy using antibody directed against CAT indicated that fusion proteins carrying 26, 50 and 101 amino acids of N-POMC were directed to secretory granules. This finding was confirmed by secretion studies in which 1 mu M forskolin stimulated the release of fusion proteins carrying 26 and 101 amino acids of N-POMC, whereas no regulated secretion was observed with the shortest fusion protein. Subcellular fractionation studies also indicated the presence of the fusion proteins with 26 and 101 amino acids of N-POMC in secretory granules. These results provide evidence that the signal directing POMC to secretory granules is contained within the N-terminus of the prohormone, with the first 26 amino acids being sufficient for targeting. Binding studies showed that N-P0MC(1-76) bound to secretory granule membranes specifically on the luminal side and in a pH-sensitive manner. Only N-POMC(1-76) bound optimally to secretory granule membranes at pH 5 to 6.5, but not the ACTH(1-39) (mid), corticotropin-like intermediate lobe peptide (CLIP) and beta lipotropin (C-terminal) domains of POMC. Such binding may be involved in the mechanism of sorting POMC to the regulated secretory pathway. C1 NICHHD,DEV NEUROBIOL LAB,CELLULAR NEUROBIOL SECT,BETHESDA,MD 20892. HOWARD HUGHES MED INST,BETHESDA,MD. NR 39 TC 61 Z9 61 U1 0 U2 0 PU WISSENSCHAFTLICHE VERLAG MBH PI STUTTGART PA BIRKENWALDSTRASSE 44, POSTFACH 10 10 61, 70009 STUTTGART, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD DEC PY 1993 VL 62 IS 2 BP 294 EP 306 PG 13 WC Cell Biology SC Cell Biology GA MP845 UT WOS:A1993MP84500011 PM 7925485 ER PT J AU ENG, CD DELGADO, R KROLL, MH AF ENG, CD DELGADO, R KROLL, MH TI COMPLEX ANALYTE-DEPENDENT AND ANALYTE-INDEPENDENT INTERFERENCES WITH CONJUGATED BILIRUBIN IN THE ENZYMATIC PHENOL-AMINOPHENAZONE PEROXIDASE (PAP) METHOD FOR CREATININE DETERMINATION SO EUROPEAN JOURNAL OF CLINICAL CHEMISTRY AND CLINICAL BIOCHEMISTRY LA English DT Article ID JAFFE METHOD; URIC-ACID; SERUM AB Although bilirubin interferes with the enzymatic assays for creatinine, neither a consensus of the degree of interference nor the mechanism has been established. Using multiple regression analysis, we demonstrate that the interference is negative and caused by both analyte-dependent and analyte-independent mechanisms. Furthermore, the correlative model includes terms non-linear with respect to creatinine. In the kinetic creatinine phenol-aminophenazone peroxidase method, there are analyte-dependent and analyte independent mechanisms at work. The multivariate equation is: Crea' = 0.9879 Crea - 0.4524 Bili - 0.000828 Crea x Bili + 2.094 x 10(-7) Crea(2) x Bili + 5.0 (Crea' = measured creatinine (mu mol/l), Crea = true creatinine (mu mol/l), and Bili = conjugated bilirubin (mu mol/l)). The endpoint mode was affected less than the kinetic mode and exhibited different relationships in which two models describe the interference equally well. One is strictly analyte-dependent: Crea' = 0.9991 Crea - 0.00203 Crea x Bili + 2.390 x 10(-6) Crea(2) x Bili - 1.464 x 10(-9) Crea(3) x Bili + 3.261 x 10(-13) Crea(4) x Bili - 9.9. The other is a complex combined analyte-dependent and analyte-independent: Crea' = 0.9834 Crea - 0.00680 Crea x Bili + 2.477 x 10(-7) Crea(2) x Bili - 3.233 x 10(-7) Crea x Bili(2) + 0.4652 Bili - 0.000458 Bili(2) + 12.2. These models are valid for creatinine concentrations up to 2200 mu mol/l (24.9 mg/dl) and bilirubin up to 660 mu mol/l (38.6 mg/dl). The interference increases with increments of either bilirubin or creatinine. In addition, we found that unconjugated bilirubin interferes differently from conjugated bilirubin in degree and mechanism. Model building, contour plots, surface plots, and possible mechanisms are discussed. We propose multiple regression analysis as the proper way to evaluate interferences because analyte-dependence can be easily missed by simple regression analysis. True creatinine concentrations can be estimated despite the interference from conjugated bilirubin. Other phenol-aminophenazone peroxidase methods may be similarly affected. RP ENG, CD (reprint author), NATL INST HLTH,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,BLDG 10,ROOM 2C407,BETHESDA,MD 20892, USA. NR 23 TC 5 Z9 5 U1 0 U2 1 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0939-4974 J9 EUR J CLIN CHEM CLIN JI Eur. J. Clin. Chem. Clin. Biochem. PD DEC PY 1993 VL 31 IS 12 BP 839 EP 850 PG 12 WC Biochemistry & Molecular Biology; Medical Laboratory Technology SC Biochemistry & Molecular Biology; Medical Laboratory Technology GA MN507 UT WOS:A1993MN50700005 PM 8136416 ER PT J AU MELZER, P CRANE, AM SMITH, CB AF MELZER, P CRANE, AM SMITH, CB TI MOUSE BARREL CORTEX FUNCTIONALLY COMPENSATES FOR DEPRIVATION PRODUCED BY NEONATAL LESION OF WHISKER FOLLICLES SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE NEONATAL PLASTICITY; MOUSE; BARREL CORTEX; QUANTITATIVE AUTORADIOGRAPHIC DEOXYGLUCOSE METHOD ID PRIMARY SOMATOSENSORY CORTEX; CEREBRAL GLUCOSE-UTILIZATION; OCULAR DOMINANCE COLUMNS; LOCAL AXON COLLATERALS; SPATIOTEMPORAL CONVERGENCE; VIBRISSAL INFORMATION; INTRINSIC CIRCUITRY; CYTOCHROME-OXIDASE; RECEPTIVE-FIELDS; CORTICAL BARRELS AB In the murine somatosensory pathway, the metabolic whisker map in barrel cortex derived with the autoradiographic deoxyglucose method is spatially in register with the morphological whisker map represented by the barrels. The barrel cortex of adult mice, in which we had removed three whisker follicles from the middle row of whiskers shortly after birth, contained a disorganized zone surrounded by enlarged barrels with partially disrupted borders. With the fully quantitative autoradiographic deoxyglucose method, we investigated in barrel cortex of such mice the magnitude and the pattern of metabolic responses evoked by the deflection of whiskers. Most remarkably, the simultaneous deflection of six whiskers neighbouring the lesion activated not only the territory of the corresponding barrels, but also the unspecifiable area intercalated between the clearly identified barrels. This metabolic whisker map, unpredictable from the morphological 'barrel' map, may reflect a functional compensation for the deficit in input. RP MELZER, P (reprint author), NIMH,CEREBRAL METAB LAB,BLDG 36,ROOM 1A05,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 54 TC 10 Z9 10 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD DEC 1 PY 1993 VL 5 IS 12 BP 1638 EP 1652 DI 10.1111/j.1460-9568.1993.tb00232.x PG 15 WC Neurosciences SC Neurosciences & Neurology GA MN588 UT WOS:A1993MN58800008 PM 8124517 ER PT J AU WELLER, M MARINI, AM FINIELSMARLIER, F MARTIN, B PAUL, SM AF WELLER, M MARINI, AM FINIELSMARLIER, F MARTIN, B PAUL, SM TI MK-801 AND MEMANTINE PROTECT CULTURED NEURONS FROM GLUTAMATE TOXICITY INDUCED BY GLUTAMATE CARBOXYPEPTIDASE-MEDIATED CLEAVAGE OF METHOTREXATE SO EUROPEAN JOURNAL OF PHARMACOLOGY-ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY SECTION LA English DT Article DE METHOTREXATE; GLUTAMATE; MK-801; MEMANTINE; CARBOXYPEPTIDASE; NEUROTOXICITY ID METHYL-D-ASPARTATE; EXCITATORY AMINO-ACIDS; GRANULE CELLS-INVITRO; INTRAVENTRICULAR INFUSION; HUNTINGTONS-CHOREA; DOSE METHOTREXATE; RECEPTOR; NEUROTOXICITY; OVERDOSE; ANTAGONISTS AB Cleavage of methotrexate into glutamate and diaminomethylpteroate by intrathecal glutamate carboxypeptidase is a new approach to the treatment of acute methotrexate neurotoxicity. The simulation of glutamate carboxypeptidase rescue from high-dose methotrexate in neuron astrocyte cocultures of rat cerebellum or cerebral cortex resulted in a selective, concentration-dependent neurotoxicity. The neurotoxicity was caused by the enzymatic release of glutamate from methotrexate at lower concentrations of methotrexate, and by both glutamate and diaminomethylpteroate at concentrations of methotrexate exceeding 200 mu M. The good neuroprotection afforded by MK-801 and memantine suggested that glutamate toxicity was mediated by N-methyl-D-aspartate receptors. Methotrexate alone was not toxic to astrocytes, neurons, or the neurite networking. [H-3]thymidine and [H-3]deoxyuridine incorporation studies showed that astrocyte proliferation in the presence of methotrexate was maintained by the reutilization of pyrimidine bases for DNA synthesis. N-methyl-D-aspartate receptor antagonists should be coadministered in future experimental and clinical trials examining intrathecal glutamate carboxypeptidase rescue of methotrexate toxicity. C1 NIMH,CLIN NEUROSCI BRANCH,MOLEC PHARMACOL SECT,BETHESDA,MD 20892. NIMH,CLIN NEUROSCI BRANCH,MOLEC NEUROGENET SECT,BETHESDA,MD 20892. NR 49 TC 18 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-6917 J9 EUR J PHARM-ENVIRON JI Eur. J. Pharmacol.-Environ. Toxicol. Pharmacol. Sect. PD DEC 1 PY 1993 VL 248 IS 4 BP 303 EP 312 DI 10.1016/0926-6917(93)90004-A PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA MV801 UT WOS:A1993MV80100004 PM 7910141 ER PT J AU HOLMES, D TERESI, J ORY, M AF HOLMES, D TERESI, J ORY, M TI SERENDIPITY AND PSEUDOSCIENCE - A LOOK AT HEALTH-RELATED PROGRAM-EVALUATION SO EVALUATION & THE HEALTH PROFESSIONS LA English DT Article ID LATENT-VARIABLES; CAUSAL; STATISTICS; LIGHT AB This article presents a discussion of the pitfalls of sloppy science as it is applied to the evaluation of human service programs. The differences are examined between use of the scientific method and trial-and-error approaches to assessment. The major requirement for sound research are presented, as are the pitfalls and shortcomings associated with a less rigorous approach. C1 COMMUNITY RES APPLICAT INC,BRONX,NY. COLUMBIA UNIV,CTR GERIATR,NEW YORK,NY 10027. NIA,BETHESDA,MD 20892. RP HOLMES, D (reprint author), HEBREW HOME AGED,RIVERDALE,NY 10471, USA. NR 18 TC 0 Z9 1 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0163-2787 J9 EVAL HEALTH PROF JI Eval. Health Prof. PD DEC PY 1993 VL 16 IS 4 BP 363 EP 378 DI 10.1177/016327879301600401 PG 16 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA MJ153 UT WOS:A1993MJ15300001 PM 10130550 ER PT J AU GERTZ, SD GIMPLE, LW RAGOSTA, M ROBERTS, WC HABER, HL POWERS, ER PEREZ, LS SAREMBOCK, IJ AF GERTZ, SD GIMPLE, LW RAGOSTA, M ROBERTS, WC HABER, HL POWERS, ER PEREZ, LS SAREMBOCK, IJ TI RESPONSE OF FEMORAL ARTERIES OF CHOLESTEROL-FED RABBITS TO BALLOON ANGIOPLASTY WITH OR WITHOUT LASER - EMPHASIS ON THE DISTRIBUTION OF FOAM CELLS SO EXPERIMENTAL AND MOLECULAR PATHOLOGY LA English DT Article ID EPICARDIAL CORONARY-ARTERIES; ATHEROSCLEROTIC PLAQUES; IMMUNOCYTOCHEMICAL ANALYSIS; SMOOTH-MUSCLE; ATHEROGENESIS; MACROPHAGES; RESTENOSIS; ANTIBODY; ANEURYSM; LESIONS AB Very little is known about the structural composition of the restenotic plaque in evolution. The responses of atherosclerotic femoral arteries of rabbits to balloon angioplasty (BA), thallium/holmium/chromium:YAG infrared laser angioplasty (LA), combined LA and BA, or no angioplasty were compared by blinded quantitative histomorphometry and angiography. The endothelium was injured by nitrogen/air desiccation, and the animals were fed a 2% cholesterol diet for 1 month prior to the angioplasty procedure. Animals were sacrificed 2 hr or 28 days after angioplasty by pressure perfusion with 10% formaldehyde (100 mm Hg), and arterial segments (4-5 cm) were excised bilaterally. The frequency of thrombus was greatest in arteries with LA. Arteries with combined LA and BA had the greatest initial gain in luminal diameter by angiography, but they also had the greatest reduction in luminal diameter from 2 hr to 28 days and the greatest cross-sectional area narrowing by plaque at 28 days. The principal component of the intimal plaques in all groups was fibrous tissue (approximately 90%), with the remainder consisting primarily of ''foam cells. '' By multiple regression analysis, the strongest predictors of cross-sectional area narrowing were contiguity of foam cells between the intima and media, depth of the tear, percentage of foam cells in the plaque, and the intervention of LA followed by BA. The principal predictors of foam cells in the plaque, irrespective of treatment, were also cross-sectional area narrowing, contiguity of foam cells between plaque and media, and the depth of tear. It is suggested that a large proportion of the foam cells of the intima may be derived from foam cells of the media and adventitia rather than from the lumen. These observations may be of particular importance regarding angioplasty in young people where foam cells occupy a significantly greater proportion of the atherosclerotic plaque. (C) 1993 Academic Press, Inc. C1 UNIV VIRGINIA,HLTH SCI CTR,DIV CARDIOL,CHARLOTTESVILLE,VA 22903. NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. RP GERTZ, SD (reprint author), HEBREW UNIV JERUSALEM,HADASSAH MED SCH,FAC MED,DEPT ANAT & EMBRYOL,IL-91120 JERUSALEM,ISRAEL. FU NHLBI NIH HHS [R01 HL47849-01] NR 25 TC 11 Z9 13 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 0014-4800 J9 EXP MOL PATHOL JI Exp. Mol. Pathol. PD DEC PY 1993 VL 59 IS 3 BP 225 EP 243 DI 10.1006/exmp.1993.1041 PG 19 WC Pathology SC Pathology GA NE035 UT WOS:A1993NE03500006 PM 8137904 ER PT J AU AFSHARI, CA VOJTA, PJ ANNAB, LA FUTREAL, PA WILLARD, TB BARRETT, JC AF AFSHARI, CA VOJTA, PJ ANNAB, LA FUTREAL, PA WILLARD, TB BARRETT, JC TI INVESTIGATION OF THE ROLE OF G(1)/S CELL-CYCLE MEDIATORS IN CELLULAR SENESCENCE SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID HUMAN-DIPLOID FIBROBLASTS; SIGNAL-REGULATED KINASES; INDEFINITE DIVISION; GENETIC-ANALYSIS; P53 PROTEIN; EXPRESSION; CDC2; DNA; PHOSPHORYLATION; IMMORTALIZATION C1 NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,CURRICULUM TOXICOL,CHAPEL HILL,NC 27599. UNIV N CAROLINA,CURRICULUM GENET,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT PATHOL,CHAPEL HILL,NC 27599. NR 44 TC 97 Z9 99 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD DEC PY 1993 VL 209 IS 2 BP 231 EP 237 DI 10.1006/excr.1993.1306 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA MM465 UT WOS:A1993MM46500009 PM 8262140 ER PT J AU BENITO, M PORRAS, A SANTOS, E AF BENITO, M PORRAS, A SANTOS, E TI ESTABLISHMENT OF PERMANENT BROWN ADIPOCYTE CELL-LINES ACHIEVED BY TRANSFECTION WITH SV40 LARGE T-ANTIGEN AND RAS GENES SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID MITOCHONDRIAL UNCOUPLING PROTEIN; PRIMARY CULTURES; ADIPOSE-TISSUE; ADRENERGIC REGULATION; HORMONAL-REGULATION; FETAL LIPOGENESIS; EXPRESSION; ONCOGENES; INSULIN; GLUCOSE-6-PHOSPHATE-DEHYDROGENASE C1 NCI,LCMB,BETHESDA,MD 20892. RI Porras, Almudena/N-2121-2015 OI Porras, Almudena/0000-0002-6495-3308 NR 23 TC 24 Z9 24 U1 0 U2 4 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 DEC PY 1993 VL 209 IS 2 BP 248 EP 254 DI 10.1006/excr.1993.1308 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA MM465 UT WOS:A1993MM46500011 PM 8262142 ER PT J AU DUFFY, M SUN, YF WIGGERT, B DUNCAN, T CHADER, GJ RIPPS, H AF DUFFY, M SUN, YF WIGGERT, B DUNCAN, T CHADER, GJ RIPPS, H TI INTERPHOTORECEPTOR RETINOID-BINDING PROTEIN (IRBP) ENHANCES RHODOPSIN REGENERATION IN THE EXPERIMENTALLY DETACHED RETINA SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE RETINAL DETACHMENT; IRBP; RHODOPSIN KINETICS; FUNDUS REFLECTOMETRY; SKATE ID PIGMENT-EPITHELIUM; SUBRETINAL FLUID; SKATE; LIGHT; 11-CIS-RETINOIDS; PHOTORECEPTORS; BIOSYNTHESIS; RETINOPATHY; ADAPTATION; INTERFACE C1 UNIV ILLINOIS,COLL MED,LIONS ILLINOIS EYE RES INST,DEPT OPHTHALMOL & VISUAL SCI,CHICAGO,IL 60612. NEI,BETHESDA,MD 20205. FU NEI NIH HHS [EY-01792, EY-06516] NR 46 TC 16 Z9 17 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD DEC PY 1993 VL 57 IS 6 BP 771 EP 782 DI 10.1006/exer.1993.1185 PG 12 WC Ophthalmology SC Ophthalmology GA MR480 UT WOS:A1993MR48000013 PM 8150029 ER PT J AU GIORDANO, M TAKASHIMA, H HERRANZ, A POLTORAK, M GELLER, HM MARONE, M FREED, WJ AF GIORDANO, M TAKASHIMA, H HERRANZ, A POLTORAK, M GELLER, HM MARONE, M FREED, WJ TI IMMORTALIZED GABAERGIC CELL-LINES DERIVED FROM RAT STRIATUM USING A TEMPERATURE-SENSITIVE ALLELE OF THE SV40 LARGE T-ANTIGEN SO EXPERIMENTAL NEUROLOGY LA English DT Note ID EPIDERMAL GROWTH-FACTOR; NEURONS; DIFFERENTIATION; INVITRO; ESTABLISHMENT; STIMULATION; VECTOR; MOUSE; BRAIN; GENE C1 UMDNJ,ROBERT WOOD JOHNSON MED SCH,DEPT PHARMACOL,PISCATAWAY,NJ 08854. RP GIORDANO, M (reprint author), ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,WASHINGTON,DC 20032, USA. OI Geller, Herbert/0000-0002-7048-6144 NR 34 TC 48 Z9 48 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD DEC PY 1993 VL 124 IS 2 BP 395 EP 400 DI 10.1006/exnr.1993.1213 PG 6 WC Neurosciences SC Neurosciences & Neurology GA MR569 UT WOS:A1993MR56900027 PM 8287936 ER PT J AU DOYLE, PS DWYER, DM AF DOYLE, PS DWYER, DM TI LEISHMANIA - IMMUNOCHEMICAL COMPARISON OF THE SECRETORY (EXTRACELLULAR) ACID-PHOSPHATASES FROM VARIOUS SPECIES SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE LEISHMANIA; SACP, EXTRACELLULAR ACID PHOSPHATASE; IMMUNOCHEMICAL COMPARISON; SECRETORY ENZYME ID DONOVANI PROMASTIGOTES; MACROPHAGES INVITRO; SURFACE-MEMBRANE; LIPOPHOSPHOGLYCAN; IDENTIFICATION; MULTIPLICATION; PARASITE; CULTURE; GROWTH C1 NIAID,PARASIT DIS LAB,CELL BIOL & IMMUNOL SECT,BETHESDA,MD 20892. NR 24 TC 29 Z9 29 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 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD DEC PY 1993 VL 77 IS 4 BP 435 EP 444 DI 10.1006/expr.1993.1103 PG 10 WC Parasitology SC Parasitology GA ML003 UT WOS:A1993ML00300006 PM 8253156 ER PT J AU CLARK, CG DIAMOND, LS AF CLARK, CG DIAMOND, LS TI ENTAMOEBA-HISTOLYTICA - A METHOD FOR ISOLATE IDENTIFICATION SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE ANTIGEN GENE; ENTAMOEBA-HISTOLYTICA; EPIDEMIOLOGY; POLYMORPHIC DNA; TANDEMLY REPEATED DNA ID PROTEIN; STRAIN RP CLARK, CG (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. RI Clark, C Graham/H-3683-2011 OI Clark, C Graham/0000-0002-0521-0977 NR 14 TC 70 Z9 71 U1 0 U2 4 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 DEC PY 1993 VL 77 IS 4 BP 450 EP 455 DI 10.1006/expr.1993.1105 PG 6 WC Parasitology SC Parasitology GA ML003 UT WOS:A1993ML00300008 PM 8253158 ER PT J AU CLARK, CG DIAMOND, LS AF CLARK, CG DIAMOND, LS TI ENTAMOEBA-HISTOLYTICA - AN EXPLANATION FOR THE REPORTED CONVERSION OF NONPATHOGENIC AMEBAE TO THE PATHOGENIC FORM SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE CONTAMINATION; ENTAMOEBA-DISPAR; ENTAMOEBA-HISTOLYTICA; ISOENZYMES; POLYMORPHIC DNA ID CROSS-CONTAMINATION; ISOENZYME PATTERNS; DNA-SEQUENCES; DIFFERENTIATION; CULTURE; STRAIN RP CLARK, CG (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. RI Clark, C Graham/H-3683-2011 OI Clark, C Graham/0000-0002-0521-0977 NR 24 TC 23 Z9 24 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD DEC PY 1993 VL 77 IS 4 BP 456 EP 460 DI 10.1006/expr.1993.1106 PG 5 WC Parasitology SC Parasitology GA ML003 UT WOS:A1993ML00300009 PM 8253159 ER PT J AU STETLERSTEVENSON, WG LIOTTA, LA KLEINER, DE AF STETLERSTEVENSON, WG LIOTTA, LA KLEINER, DE TI EXTRACELLULAR MATRIX-6 - ROLE OF MATRIX METALLOPROTEINASES IN TUMOR INVASION AND METASTASIS SO FASEB JOURNAL LA English DT Review DE CELL INVASION; METASTASIS; MATRIX METALLOPROTEASES ID BASEMENT-MEMBRANE MATRIGEL; CONSERVED PEPTIDE SEQUENCE; HUMAN-TISSUE INHIBITOR; C-TERMINAL DOMAIN; IV COLLAGENASE; PLASMINOGEN-ACTIVATOR; ENDOTHELIAL-CELLS; INTERSTITIAL COLLAGENASE; PROTEOLYTIC ACTIVITY; CANCER METASTASIS AB Over the course of these Serial Reviews the reader has been made aware of the growing importance of the extracellular matrix in modern cell biology. The matrix not only has a mechanical role in maintaining the integrity of the tissues, but also controls the flow of nutrients and signals to the cells, and indeed, provides many of these signals. There are a number of pathological situations in which cells cause excessive degradation of their own matrix, e.g., osteoarthritis, periodontitis and decubitus ulcer. One of the most striking examples of unbridled attack upon the matrix is seen in the process of tumor invasion and metastasis. All barriers to cell movement through tissues and into vessels are obliterated, largely through the action of a battery-of extracellular metalloproteinases. The regulation of these proteinases in cancer is the subject of this review. RP STETLERSTEVENSON, WG (reprint author), NCI,DCBDC,PATHOL LAB,BLDG 10,ROOM 2A33,BETHESDA,MD 20892, USA. RI Stetler-Stevenson, William/H-6956-2012; OI Stetler-Stevenson, William/0000-0002-5500-5808; Kleiner, David/0000-0003-3442-4453 NR 78 TC 499 Z9 511 U1 0 U2 8 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 DEC PY 1993 VL 7 IS 15 BP 1434 EP 1441 PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ML740 UT WOS:A1993ML74000005 PM 8262328 ER PT J AU CONE, EJ DARWIN, WD WANG, WL AF CONE, EJ DARWIN, WD WANG, WL TI THE OCCURRENCE OF COCAINE, HEROIN AND METABOLITES IN HAIR OF DRUG-ABUSERS SO FORENSIC SCIENCE INTERNATIONAL LA English DT Article; Proceedings Paper CT 1st International Meeting on Hair Analysis as a Diagnostic Tool for Drugs of Abuse Investigation CY DEC 10-11, 1992 CL GENOA, ITALY SP UN INTERREG CRIME & JUSTICE RES INST, IST SUPER SANITA, INT ASSOC FORENS TOXICOLOGISTS, NIGUARDA CA GRANDA HOSP DE COCAINE; BENZOYLECGONINE; HEROIN; 6-ACETYLMORPHINE; HAIR ANALYSIS ID CHROMATOGRAPHY MASS-SPECTROMETRY; TESTING HUMAN HAIR; IDENTIFICATION; QUANTITATION AB The analysis of hair for drugs of abuse reveals information regarding past drug exposure. We developed methods for washing, extraction and analysis of hair samples for cocaine, heroin and metabolites. Twenty paired head- and arm-hair samples, collected from known heroin/cocaine abusers, were analyzed with a new comprehensive GC/MS assay for cocaine, heroin and metabolites. Cocaine and 6-acetylmorphine (6-AM) were the major analytes present in both head- and arm-hair samples. Cocaine was detected in all head- and 17 arm-hair samples. The concentration of cocaine found was 4-760 ng/10 mg in head hair and 0-1090 ng/10 mg in arm hair. Less benzoylecgonine was present in a concentration range of 0-158 ng/10 mg of head hair and 0-125 ng/10 mg of arm hair. Heroin was found in only 2 head-hair samples, whereas 6-AM was present in 14 head and 6 arm-hair samples. The concentration of 6-AM was 0-8 ng/10 mg in head hair and 0-31 ng/10 mg in arm hair. Morphine was present in 3 head-hair samples in a range of 2-9 ng/10 mg and was not detected in arm-hair samples. When results were compared by groups (head hair versus arm hair, Caucasoid versus Africoid), only two significant differences were found. Cocaine concentrations in both head and arm hair were significantly (P < 0.05) higher in the Africoid group than in the Caucasoid group. The reasons for these differences were not readily apparent, but could have been due to differences in the level of cocaine use or to ethnic differences in the deposition of drug in hair. RP CONE, EJ (reprint author), NATL INST DRUG ABUSE,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224, USA. NR 13 TC 58 Z9 61 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0379-0738 J9 FORENSIC SCI INT JI Forensic Sci.Int. PD DEC PY 1993 VL 63 IS 1-3 BP 55 EP 68 DI 10.1016/0379-0738(93)90259-D PG 14 WC Medicine, Legal SC Legal Medicine GA MY442 UT WOS:A1993MY44200007 PM 8138234 ER PT J AU LIU, YB ROSENTHAL, RE STARKEREED, P FISKUM, G AF LIU, YB ROSENTHAL, RE STARKEREED, P FISKUM, G TI INHIBITION OF POSTCARDIAC ARREST BRAIN PROTEIN OXIDATION BY ACETYL-L-CARNITINE SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Note DE PROTEIN OXIDATION; CARBONYL GROUPS; CEREBRAL ISCHEMIA; ACETYL-L-CARNITINE; FREE RADICALS ID LIPID-PEROXIDATION; FREE-RADICALS; ISCHEMIA; REPERFUSION; DAMAGE; INJURY AB Free radical mediated, site-specific protein oxidation has been implicated in the pathophysiology of ischemia/reperfusion brain injury. The purpose of this study was to determine whether this form of molecular damage could be detected in a clinically relevant model employing 10-min cardiac arrest in dogs followed by restoration of spontaneous circulation for up to 24 h. The effects of postischemic acetyl-L-carnitine administration on protein oxidation were also tested due to its previously reported improvement of brain energy metabolism and neurological outcome in this model. Following the experimental period, soluble proteins were extracted from a sample of frontal cortex and reacted with dinitrophenylhydrazine for spectrophotometric measurement of protein carbonyl groups. The most important results of this study were that brain protein carbonyl groups were significantly elevated following 2 and 24 h of reperfusion compared to nonischemic controls, and that postischemic IV administration of acetyl-L-carnitine eliminated the increase in carbonyl groups observed at the 24-h period. These results indicate that brain protein oxidation does occur in a clinically relevant model of complete global cerebral ischemia and reperfusion, and that oxidation is inhibited under treatment conditions that improve neurological outcome. C1 GEORGE WASHINGTON UNIV,SCH MED,DEPT BIOCHEM & MOLEC BIOL,WASHINGTON,DC 20037. NIH,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,SCH MED,DEPT EMERGENCY MED,WASHINGTON,DC 20037. NR 11 TC 47 Z9 48 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD DEC PY 1993 VL 15 IS 6 BP 667 EP 670 DI 10.1016/0891-5849(93)90171-P PG 4 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA MJ387 UT WOS:A1993MJ38700014 PM 8138193 ER PT J AU SHIRAKATA, M FRIEDMAN, FK WEI, Q PATERSON, BM AF SHIRAKATA, M FRIEDMAN, FK WEI, Q PATERSON, BM TI DIMERIZATION SPECIFICITY OF MYOGENIC HELIX-LOOP-HELIX DNA-BINDING FACTORS DIRECTED BY NONCONSERVED HYDROPHILIC RESIDUES SO GENES & DEVELOPMENT LA English DT Article DE TRANSCRIPTIONAL FACTOR; DOMINANT NEGATIVE MUTANT; MUSCLE DEVELOPMENT; GENE REGULATION; SITE-DIRECTED MUTAGENESIS ID TRANSCRIPTION FACTORS; LEUCINE-ZIPPER; MYC HOMOLOGY; C-MYC; PROTEIN; MYOD; DOMAIN; ENHANCER; GENE; FIBROBLASTS AB The myogenic regulatory factor MyoD dimerizes with other positive and negative regulatory factors through a conserved region called the helix-loop-helix (HLH) domain. Using a non-DNA-binding MyoD mutant with a normal HLH domain as a dimerization competitor in gel mobility shift assays in conjunction with various MyoD HLH mutants, nonhydrophobic amino acids were identified in the HLH domain that contribute to dimerization specificity with E12. The assay detected subtle differences in dimerization activity among the mutant MyoD proteins that correlated with their ability to activate transcription in vivo, but this correlation was not apparent in the absence of competitor. The identification of such nonhydrophobic residues enabled us to predict the differences in dimerization affinity among the four vertebrate myogenic factors with E12. The experiments confirmed the prediction. Furthermore, a high-affinity homodimerizing analog of MyoD was designed by a single substitution at one of these residue positions. These experimental results were strengthened when they were analyzed in terms of the crystal structure for the Max bHLHZip domain homodimer. This analysis has allowed us to identify those residues that form charged residue pairs between the two HLH domains of MyoD and E12 and determine the dimerization specificity of the bHLH proteins. C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RP SHIRAKATA, M (reprint author), NCI,BIOCHEM LAB,BETHESDA,MD 20892, USA. RI Friedman, Fred/D-4208-2016 NR 56 TC 54 Z9 54 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD DEC PY 1993 VL 7 IS 12A BP 2456 EP 2470 DI 10.1101/gad.7.12a.2456 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA ML381 UT WOS:A1993ML38100016 PM 8253390 ER PT J AU HASTINGS, PJ MCGILL, C SHAFER, B STRATHERN, JN AF HASTINGS, PJ MCGILL, C SHAFER, B STRATHERN, JN TI ENDS-IN VS ENDS-OUT RECOMBINATION IN YEAST SO GENETICS LA English DT Article ID DOUBLE-STRAND BREAKS; SACCHAROMYCES-CEREVISIAE; MODEL; REPAIR; DNA; CONSTRUCTION; SYSTEM AB Integration of linearized plasmids into yeast chromosomes has been used as a model system for the study of recombination initiated by double-strand breaks. The linearized plasmid DNA recombines efficiently into sequences homologous to the ends of the DNA. This efficient recombination occurs both for the configuration in which the break is in a contiguous region of homology (herein called the ends-in configuration) and for ''omega'' insertions in which plasmid sequences interrupt a linear region of homology (herein called the ends-out configuration). The requirements for integration of these two configurations are expected to be different. We compared these two processes in a yeast strain containing an ends-in target and an ends-out target for the same cut plasmid. Recovery of ends-in events exceeds ends-out events by two- to threefold. Possible causes for the origin of this small bias are discussed. The lack of an extreme difference in frequency implies that cooperativity between the two ends does not contribute to the efficiency with which cut circular plasmids are integrated. This may also be true for the repair of chromosomal double-strand breaks. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,EUKARYOT GENE EXPRESS LAB,FREDERICK,MD 21702. RP HASTINGS, PJ (reprint author), UNIV ALBERTA,DEPT GENET,EDMONTON T6G 2E9,AB,CANADA. FU NCI NIH HHS [N01-CO74101] NR 21 TC 54 Z9 55 U1 0 U2 2 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD DEC PY 1993 VL 135 IS 4 BP 973 EP 980 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA MH938 UT WOS:A1993MH93800005 PM 8307337 ER PT J AU TSIOTRA, PC KARAGOGEOS, D THEODORAKIS, K MICHAELIDIS, TM MODI, WS FURLEY, AJ JESSELL, TM PAPAMATHEAKIS, J AF TSIOTRA, PC KARAGOGEOS, D THEODORAKIS, K MICHAELIDIS, TM MODI, WS FURLEY, AJ JESSELL, TM PAPAMATHEAKIS, J TI ISOLATION OF THE CDNA AND CHROMOSOMAL LOCALIZATION OF THE GENE (TAX1) ENCODING THE HUMAN AXONAL GLYCOPROTEIN TAG-1 SO GENOMICS LA English DT Article ID NEURAL CELL-ADHESION; IMMUNOGLOBULIN SUPERFAMILY; NEURITE OUTGROWTH; PROMOTING ACTIVITY; FIBRONECTIN; MOLECULE; RECOGNITION; RECEPTORS; GROWTH; IDENTIFICATION C1 FORTH,IMBB,GR-71110 IRAKLION,GREECE. UNIV CRETE,DEPT BIOL,GR-71110 IRAKLION,GREECE. UNIV CRETE,SCH MED,DEPT BASIC SCI,GR-71110 IRAKLION,GREECE. FREDERICK CANC RES & DEV CTR,BCDP DYNCORP,PROGRAM RESOURCES INC,FREDERICK,MD 21702. COLUMBIA UNIV COLL PHYS & SURG,HOWARD HUGHES MED INST,NEW YORK,NY 10032. COLUMBIA UNIV COLL PHYS & SURG,DEPT BIOCHEM & MOLEC BIOPHYS,NEW YORK,NY 10032. RI Furley, Andrew/D-4798-2013 NR 35 TC 25 Z9 26 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD DEC PY 1993 VL 18 IS 3 BP 562 EP 567 DI 10.1016/S0888-7543(05)80357-X PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA MP480 UT WOS:A1993MP48000014 PM 8307567 ER PT J AU REITMAN, M GRASSO, JA BLUMENTHAL, R LEWIT, P AF REITMAN, M GRASSO, JA BLUMENTHAL, R LEWIT, P TI PRIMARY SEQUENCE, EVOLUTION, AND REPETITIVE ELEMENTS OF THE GALLUS-GALLUS (CHICKEN) BETA-GLOBIN CLUSTER SO GENOMICS LA English DT Article ID LOCUS ACTIVATION REGION; NUCLEOTIDE-SEQUENCE; GENE REGION; DEVELOPMENTAL REGULATION; HYPERSENSITIVE SITES; INTERSPERSED REPEATS; DNA METHYLATION; ERYTHROID-CELLS; TRANSGENIC MICE; EPSILON-GLOBIN C1 UNIV CONNECTICUT,CTR HLTH,FARMINGTON,CT 06030. RP REITMAN, M (reprint author), NIDDKD,DIABET BRANCH,BLDG 10,ROOM 8N250,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Reitman, Marc/B-4448-2013 OI Reitman, Marc/0000-0002-0426-9475 NR 77 TC 39 Z9 43 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD DEC PY 1993 VL 18 IS 3 BP 616 EP 626 DI 10.1016/S0888-7543(05)80364-7 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA MP480 UT WOS:A1993MP48000021 PM 8307571 ER PT J AU RUTHERFORD, MS ROCK, CO JENKINS, NA GILBERT, DJ TESSNER, TG COPELAND, NG JACKOWSKI, S AF RUTHERFORD, MS ROCK, CO JENKINS, NA GILBERT, DJ TESSNER, TG COPELAND, NG JACKOWSKI, S TI THE GENE FOR MURINE CTP-PHOSPHOCHOLINE CYTIDYLYLTRANSFERASE (CTPCT) IS LOCATED ON MOUSE CHROMOSOME-16 SO GENOMICS LA English DT Note ID CLONING C1 ST JUDE CHILDRENS RES HOSP, DEPT BIOCHEM, MEMPHIS, TN 38101 USA. UNIV TENNESSEE, DEPT BIOCHEM, MEMPHIS, TN 38163 USA. NCI, FREDERICK CANC RES & DEV CTR, ABL, BASIC RES PROGRAM, FREDERICK, MD 21702 USA. FU NCI NIH HHS [T32 CA09346, CA21765]; NIGMS NIH HHS [GM45737] NR 13 TC 25 Z9 26 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD DEC PY 1993 VL 18 IS 3 BP 698 EP 701 DI 10.1016/S0888-7543(05)80377-5 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA MP480 UT WOS:A1993MP48000034 PM 8307580 ER PT J AU BUTLER, RN AHRONHEIM, J FILLIT, H RAPOPORT, SI TATEMICHI, TK AF BUTLER, RN AHRONHEIM, J FILLIT, H RAPOPORT, SI TATEMICHI, TK TI VASCULAR DEMENTIA - HOW TO MAKE THE DIAGNOSIS IN OFFICE PRACTICE - A ROUND-TABLE DISCUSSION .2. SO GERIATRICS LA English DT Article AB Vascular dementia is seen much more often in people at age 85 than in those between the ages of 55 and 75. The differential diagnosis includes Alzheimer's disease and mixed dementia. The classic criteria for vascular dementia-stepwise deterioration and focal neurologic signs-are important, as focal neurologic signs usually don't occur in Alzheimer's disease. Identifying a significant number of points on the Hachinski scale, including hypertension, can help make a diagnosis of vascular disease. For more effective differential diagnosis, CT or MRI can be useful. However, not all clinicians are convinced of the necessity of imaging, as long as stroke risk factors such as hypertension and hyperlipidemia are managed for all older patients. C1 MT SINAI MED CTR,GERIATR CONSULTAT & LIAISON SERV,NEW YORK,NY 10029. NIA,NEUROSCI LAB,BETHESDA,MD 20892. COLUMBIA UNIV COLL PHYS & SURG,INST NEUROL,STROKE & AGING RES PROJECT,NEW YORK,NY 10032. RP BUTLER, RN (reprint author), CUNY MT SINAI SCH MED,DEPT GERIATR & ADULT DEV,NEW YORK,NY 10029, USA. NR 3 TC 7 Z9 7 U1 0 U2 1 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 SN 0016-867X J9 GERIATRICS JI Geriatrics PD DEC PY 1993 VL 48 IS 12 BP 39 EP & PG 0 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA ML945 UT WOS:A1993ML94500004 PM 8253393 ER PT J AU KASHIMA, K UNSER, M DATILES, MB TRUS, BL EDWARDS, PA AF KASHIMA, K UNSER, M DATILES, MB TRUS, BL EDWARDS, PA TI MINIMUM VIEWS REQUIRED TO CHARACTERIZE CATARACTS WHEN USING THE SCHEIMPFLUG CAMERA SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article ID RETROILLUMINATION AB We performed Scheimpflug slit lamp photography and computerized image analysis on 20 normal and 25 cataractous tenses using 18 slit images for each lens taken 10-degrees apart. The data gathered from the normals served as the reference to estimate the accuracy of representation of the cataracts by the least number of views (18 and less) using a Fourier interpolative algorithm. Using the error obtained with one view for the normals. our study suggests that the minimum number of views necessary for adequate characterization is two for cortical cataracts, two for nuclear cataracts, and six for posterior subcapsular cataracts. This information will be useful in longitudinal studies of cataracts, since most researchers presently use only one view, which may be adequate for normals but not for cataractous lenses. We found the Fourier interpolative algorithm useful in estimating the minimum views required for the current method of analyzing Scheimpflug images, and it can be easily applied to other similar images. C1 NEI,OG&CS BRANCH,CATARACT & CORNEAL DIS SECT,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,COMP SYST LAB,BETHESDA,MD 20892. RI Unser, Michael/A-1550-2008; OI Datiles, Manuel III B./0000-0003-4660-1664 NR 9 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD DEC PY 1993 VL 231 IS 12 BP 687 EP 691 DI 10.1007/BF00919282 PG 5 WC Ophthalmology SC Ophthalmology GA MK077 UT WOS:A1993MK07700003 PM 8299975 ER PT J AU BRINTON, LA HERRERO, R REEVES, WC DEBRITTON, RC GAITAN, E TENORIO, F AF BRINTON, LA HERRERO, R REEVES, WC DEBRITTON, RC GAITAN, E TENORIO, F TI RISK-FACTORS FOR CERVICAL-CANCER BY HISTOLOGY SO GYNECOLOGIC ONCOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; UTERINE CERVIX; PRIMARY ADENOCARCINOMA; YOUNG-WOMEN; ENDOCERVIX; PROGNOSIS; FEATURES C1 CAJA COSTARRICENSE SEGURO SOCIAL,DEPT MED PREVENT,SAN JOSE,COSTA RICA. CTR DIS CONTROL,VIRAL EXANTHEMS & HERPESVIRUS BRANCH,ATLANTA,GA. INST ONCOL NACL,PANAMA CITY,PANAMA. INST NACL CANCEROL,DIV EPIDEMIOL,BOGOTA,COLOMBIA. HOSP NACL ONCOL,INST MEXICANO SEGURO SOCIAL,MEXICO CITY,DF,MEXICO. RP BRINTON, LA (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 36 TC 48 Z9 54 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 1993 VL 51 IS 3 BP 301 EP 306 DI 10.1006/gyno.1993.1294 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA MW768 UT WOS:A1993MW76800003 PM 8112636 ER PT J AU RICHARDSON, MA SIMONSMORTON, B ANNEGERS, JF AF RICHARDSON, MA SIMONSMORTON, B ANNEGERS, JF TI EFFECT OF PERCEIVED BARRIERS ON COMPLIANCE WITH ANTIHYPERTENSIVE MEDICATION SO HEALTH EDUCATION QUARTERLY LA English DT Article ID HYPERTENSIVE PATIENTS; ADHERENCE; RISK; QUALITY; IMPACT; LOCUS; CARE; LIFE AB Noncompliance with antihypertensive medication remains an obstacle to the management of hypertension, and despite research efforts over the past decade, the predictors of noncompliance remain unclear. According to values expectancy theory, individuals rationally choose noncompliance when the barriers or costs of treatment outweigh the expected benefits. Noncompliance, therefore, is likely to occur when net costs of treatment are high. Using a cross-sectional study design among subjects (n = 197) attending a specialized clinic for hypertension, we measured ''net barriers'' (costs), self-reported compliance, and possible determinants of noncompliance, including sociodemographics, the medical regimen, and locus of control. The effect of each quartile of the net barriers score (none, low, moderate, and high) on compliance, controlling for potential effect modifiers, was assessed using logistic regression modeling. Noncompliance (47%) was associated with younger age, higher salt use, longer duration of treatment, and higher levels of net barriers, but duration of treatment modified the effect of net barriers. Among subjects in short-term treatment, noncompliance increased with severity of net barriers suggesting a dose-response effect. In contrast, patients in long-term treatment showed no dose-response effect but a consistent association between noncompliance and levels of net barriers. Subjects at greatest risk for noncompliance, however, were those who reported high net barriers, regardless of duration of treatment. Net barriers accounted for 50% of the noncompliance and appeared most important for patients who were younger or in the early stages of treatment. Implications for health care providers are discussed. C1 NICHHD,DESPR,PREVENT RES BRANCH,ROCKVILLE,MD. UNIV TEXAS,HLTH SCI CTR,SCH PUBL HLTH,DIV EPIDEMIOL,HOUSTON,TX 77225. RP RICHARDSON, MA (reprint author), UNIV TEXAS,HLTH SCI CTR,SCH PUBL HLTH,CTR HLTH PROMOT RES & DEV,HOUSTON,TX 77225, USA. OI Simons-Morton, Bruce/0000-0003-1099-6617 NR 50 TC 39 Z9 40 U1 4 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0195-8402 J9 HEALTH EDUC QUART JI Health Educ. Q. PD WIN PY 1993 VL 20 IS 4 BP 489 EP 503 DI 10.1177/109019819302000409 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA MJ129 UT WOS:A1993MJ12900003 PM 8307768 ER PT J AU FONG, TL DIBISCEGLIE, AM GERBER, MA WAGGONER, JG HOOFNAGLE, JH AF FONG, TL DIBISCEGLIE, AM GERBER, MA WAGGONER, JG HOOFNAGLE, JH TI PERSISTENCE OF HEPATITIS-B VIRUS-DNA IN THE LIVER AFTER LOSS OF HBSAG IN CHRONIC HEPATITIS-B SO HEPATOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; ALPHA-INTERFERON THERAPY; SURFACE-ANTIGEN; HEPATOCELLULAR-CARCINOMA; CONTROLLED TRIAL; SERUM; DISEASE; SEROCONVERSION; INFECTION; RNA AB To determine whether patients with chronic hepatitis B who lose hepatitis B virus DNA and HBsAg from the serum completely resolve the hepatitis and virus infection, we evaluated serum and liver tissue from 11 patients who had lost HBsAg. These patients were evaluated for clinical, histological and serological features and for hepatitis B virus DNA by use of hybridization and polymerase chain reaction techniques. Liver biochemical test results were normal in all except two patients who had mild aminotransferase elevations. All sera were negative for hepatitis B virus DNA by direct hybridization, and only one was positive transiently by polymerase chain reaction. Liver histology was abnormal in all patients, but the changes were mild and markedly improved compared with biopsy specimens taken before loss of HBsAg. Liver tissue from 10 patients was positive for hepatitis B virus DNA by polymerase chain reaction but not by direct hybridization. These findings indicate that loss of HBsAg is associated with marked improvements in clinical and serum biochemical features of chronic hepatitis B, yet mild degrees of hepatitis and low levels of viral DNA may persist in the liver (HEPATOLOGY 1993;18:1313-1318. C1 NIDDKD,DIGEST DIS BRANCH,LIVER DIS SECT,BLDG 31,ROOM 9A23,BETHESDA,MD 20892. TULANE UNIV,SCH MED,DEPT PATHOL,NEW ORLEANS,LA 70112. NR 35 TC 125 Z9 129 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 1993 VL 18 IS 6 BP 1313 EP 1318 DI 10.1016/0270-9139(93)90217-B PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA MJ626 UT WOS:A1993MJ62600004 PM 8244254 ER PT J AU BREIER, A BUCHANAN, RW IRISH, D CARPENTER, WT AF BREIER, A BUCHANAN, RW IRISH, D CARPENTER, WT TI CLOZAPINE TREATMENT OF OUTPATIENTS WITH SCHIZOPHRENIA - OUTCOME AND LONG-TERM RESPONSE PATTERNS SO HOSPITAL AND COMMUNITY PSYCHIATRY LA English DT Article ID QUALITY; LIFE AB Objective: The purpose of the study was to examine the effects of clozapine in treating moderately ill schizophrenic outpatients and to determine the length of medication trial needed to identify responders and nonresponders. Methods: Rates of clinical response, relapses and hospitalizations, and levels of symptomatology and functioning were assessed for 30 chronic schizophrenic outpatients who received clozapine for one year. For some patients, data on relapse and hospitalization during treatment were compared with data from the year before treatment. Results: Eighteen of the 30 Patients met criteria for sustained response, 17 of the responders were identified within the first four months of treatment. Patients experienced significantly fewer relapses and hospitalizations during treatment than in the previous year. Improvement in positive symptoms, general symptomatology, and levels of functioning reached a plateau during the first six months of treatment and remained at that level during the second six months. Negative symptoms and quality of life showed nonsignificant improvements at 12 months. Conclusions: Results support the use of clozapine in treating chronic, residually symptomatic schizophrenic outpatients. A four-month clozapine trial may be adequate to detect clinical responders in this population. C1 UNIV MARYLAND,SCH MED,DEPT PSYCHIAT,BALTIMORE,MD 21201. NIMH,DEPT EXPTL THERAPEUT,BETHESDA,MD 20892. RP BREIER, A (reprint author), MARYLAND PSYCHIAT RES CTR,POB 21247,BALTIMORE,MD 21228, USA. FU NIMH NIH HHS [MH40279, MH45074] NR 16 TC 82 Z9 84 U1 2 U2 2 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0022-1597 J9 HOSP COMMUNITY PSYCH PD DEC PY 1993 VL 44 IS 12 BP 1145 EP 1149 PG 5 WC Public, Environmental & Occupational Health; Psychiatry SC Public, Environmental & Occupational Health; Psychiatry GA MK091 UT WOS:A1993MK09100004 PM 8132186 ER PT J AU YAO, M LATIF, F ORCUTT, ML KUZMIN, I STACKHOUSE, T ZHOU, FW TORY, K DUH, FM RICHARDS, F MAHER, E LAFORGIA, S HUEBNER, K LEPASILIER, D LINEHAN, M LERMAN, M ZBAR, B AF YAO, M LATIF, F ORCUTT, ML KUZMIN, I STACKHOUSE, T ZHOU, FW TORY, K DUH, FM RICHARDS, F MAHER, E LAFORGIA, S HUEBNER, K LEPASILIER, D LINEHAN, M LERMAN, M ZBAR, B TI VON HIPPEL-LINDAU DISEASE - IDENTIFICATION OF DELETION MUTATIONS BY PULSED-FIELD GEL-ELECTROPHORESIS SO HUMAN GENETICS LA English DT Article ID RENAL-CELL CARCINOMA; GENETIC-LINKAGE ANALYSIS; HUMAN CHROMOSOME-3; SMALL REGION; SHORT ARM; LOCUS; CONSTRUCTION; POLYMORPHISM; MAPS AB Von Hippel-Lindau disease (VHL) is an inherited multisystem neoplastic disorder. We prepared a 2.5-megabase (Mb) restriction map of the region surrounding the VHL gene and identified and characterized overlapping deletions in three unrelated patients affected with VHL. The smallest nested deletion (100 kb) was located within a 510-kb NruI fragment detected by 19-63'. The rearrangements detected will be useful in isolating and evaluating candidate cDNAs for the VHL gene. The detailed physical map will be useful in studying the organization and structure of genes in the VHL region. C1 NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 21701. DYN CORP,PROGRAM RESOURCES INC,FREDERICK,MD 21702. UNIV CAMBRIDGE,SCH MED,CAMBRIDGE,CAMBS,ENGLAND. THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,PHILADELPHIA,PA 19107. CTR ETUD POLYMORPHISME HUMAIN,PARIS,FRANCE. NCI,SURG BRANCH,BETHESDA,MD 20892. RI MAHER, EAMONN/A-9507-2008 OI MAHER, EAMONN/0000-0002-6226-6918 NR 36 TC 40 Z9 40 U1 0 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD DEC PY 1993 VL 92 IS 6 BP 605 EP 614 DI 10.1007/BF00420947 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA MN013 UT WOS:A1993MN01300015 PM 8262521 ER PT J AU ROTH, M MEDEIROS, LJ KAPUR, S WEXLER, LH MIMS, S HOROWITZ, ME TSOKOS, M AF ROTH, M MEDEIROS, LJ KAPUR, S WEXLER, LH MIMS, S HOROWITZ, ME TSOKOS, M TI MALIGNANT SCHWANNOMA WITH MELANOCYTIC AND NEUROEPITHELIAL DIFFERENTIATION IN AN INFANT WITH CONGENITAL GIANT MELANOCYTIC NEVUS - A COMPLEX NEUROCRISTOPATHY SO HUMAN PATHOLOGY LA English DT Note DE NEUROCRISTOPATHY; MALIGNANT SCHWANNOMA; CONGENITAL; PIGMENTED GIANT NEVUS ID DISEASE; NEOPLASMS; TUMORS C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. RHODE ISL HOSP,DEPT PATHOL,PROVIDENCE,RI 02902. BROWN UNIV,SCH MED,PROVIDENCE,RI 02912. CHILDRENS NATL MED CTR,DEPT PATHOL,WASHINGTON,DC. RP ROTH, M (reprint author), NCI,PATHOL LAB,BLDG 10,ROOM 2N212,BETHESDA,MD 20892, USA. NR 20 TC 21 Z9 22 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD DEC PY 1993 VL 24 IS 12 BP 1371 EP 1375 DI 10.1016/0046-8177(93)90273-J PG 5 WC Pathology SC Pathology GA MR673 UT WOS:A1993MR67300015 PM 8276386 ER PT J AU HRABA, T BAKER, PJ TAYLOR, CE FAUNTLEROY, MB STASHAK, PW AF HRABA, T BAKER, PJ TAYLOR, CE FAUNTLEROY, MB STASHAK, PW TI THE INFLUENCE OF MONOPHOSPHORYL LIPID A (MPL((TM))) ON ERYTHROCYTE AUTOANTIBODY FORMATION SO IMMUNOBIOLOGY LA English DT Article ID T-CELL ACTIVITY; ANTIBODY-RESPONSE; NORMAL MICE; SUPPRESSOR; ENDOTOXIN; ADJUVANT; INACTIVATION; INDUCTION; INJECTION AB The onset and the amount of erythrocyte autoantibodies induced by the injection of C57BL/6N mice with rat red blood cells (RRBC) were hastened and increased, respectively, after the administration of monophosphoryl lipid A (MpLT(TM)); this was not the case for similarly treated BALB/cAnN mice, which make a lower autoantibody response after immunization with RRBC. The transfer of spleen cells from donor C57BL/6N mice immunized with RRBC suppressed autoantibody formation in recipient mice subsequently immunized with RRBC; however, treatment with MpL(TM) prevented neither the induction nor the expression of such suppression. This suggests that the increased autoantibody response in RRBC-immunized C57BL/6N mice treated with MPL(TM) is not due to the inactivation of suppressor cell activity which, in other studies, was found to be extremely sensitive to MPL(TM). C1 NIAID,IMMUNOGENET LAB,TWINBROOK 2 RES FACIL,ROCKVILLE,MD 20852. NR 21 TC 0 Z9 0 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0171-2985 J9 IMMUNOBIOLOGY JI Immunobiology PD DEC PY 1993 VL 189 IS 5 BP 448 EP 456 PG 9 WC Immunology SC Immunology GA MN577 UT WOS:A1993MN57700003 PM 8125521 ER PT J AU THOMAS, DL QUINN, TC AF THOMAS, DL QUINN, TC TI SEROLOGIC TESTING FOR SEXUALLY-TRANSMITTED DISEASES SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-C VIRUS; HERPES-SIMPLEX VIRUS; NON-B-HEPATITIS; LINKED IMMUNOSORBENT-ASSAY; HEMAGGLUTINATION TREPONEMAL TEST; RECOMBINANT IMMUNOBLOT ASSAY; NON-A-HEPATITIS; BORNE NON-A; HIV-INFECTION C1 JOHNS HOPKINS UNIV,SCH MED,DIV INFECT DIS,ROSE RES BLDG,SUITE 1159,720 RUTLAND AVE,BALTIMORE,MD 21205. NIAID,BETHESDA,MD 20892. NR 195 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 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD DEC PY 1993 VL 7 IS 4 BP 793 EP 824 PG 32 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA MN575 UT WOS:A1993MN57500005 PM 8106730 ER PT J AU STRATTON, P ALEXANDER, NJ AF STRATTON, P ALEXANDER, NJ TI PREVENTION OF SEXUALLY-TRANSMITTED INFECTIONS - PHYSICAL AND CHEMICAL BARRIER METHODS SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ORAL-CONTRACEPTIVE USE; HIV-INFECTION; CONDOM USE; NEISSERIA-GONORRHOEAE; CHLAMYDIA-TRACHOMATIS; HUMAN PAPILLOMAVIRUS; VENEREAL-DISEASE; CLINICAL-TRIAL; IN-VITRO RP ALEXANDER, NJ (reprint author), NICHHD,CTR POPULAT RES,CONTRACEPT DEV BRANCH,6100 EXECUT BLVD,RM 8B13,BETHESDA,MD 20892, USA. NR 91 TC 19 Z9 20 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD DEC PY 1993 VL 7 IS 4 BP 841 EP 859 PG 19 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA MN575 UT WOS:A1993MN57500007 PM 8106732 ER PT J AU COHEN, MS HOOK, EW HITCHCOCK, PJ AF COHEN, MS HOOK, EW HITCHCOCK, PJ TI SEXUALLY-TRANSMITTED DISEASES IN THE AIDS ERA .1. PREFACE SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 UNIV ALABAMA,SCH MED,BIRMINGHAM,AL 35233. NIH,DIV MICROBIOL & INFECT DIS,STD BRANCH,BETHESDA,MD 20892. RP COHEN, MS (reprint author), UNIV N CAROLINA,DEPT MED,DIV INFECT DIS,547 BURNETT WOMACK,CB 7030,CHAPEL HILL,NC 27599, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD DEC PY 1993 VL 7 IS 4 BP R11 EP R12 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA MN575 UT WOS:A1993MN57500001 ER PT J AU HARINDRANATH, N IKEMATSU, H NOTKINS, AL CASALI, P AF HARINDRANATH, N IKEMATSU, H NOTKINS, AL CASALI, P TI STRUCTURE OF THE V(H) AND V(L) SEGMENTS OF POLYREACTIVE AND MONOREACTIVE HUMAN NATURAL ANTIBODIES TO HIV-1 AND ESCHERICHIA-COLI BETA-GALACTOSIDASE SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE COMPLIMENTARITY DETERMINING REGION; FRAMEWORK REGION; IG VH AND VL SEGMENTS; NATURAL ANTIBODIES; POLYREACTIVITY ID IMMUNOGLOBULIN HEAVY-CHAIN; GERM-LINE GENES; VARIABLE REGION GENES; SYSTEMIC LUPUS-ERYTHEMATOSUS; B CAPSULAR POLYSACCHARIDE; ANTI-DNA ANTIBODIES; SOMATIC MUTATION; VH-GENE; RHEUMATOID FACTORS; IMMUNE-RESPONSE AB B lymphocytes committed to the production of antibodies binding to antigens on pathogenic bacteria and viruses (natural antibodies) are common components of the normal human B cell repertoire. A major proportion of natural antibodies is capable of binding multiple antigens (polyreactive antibodies). Using B cells from three HIV-1 seronegative healthy subjects, and purified HIV-1 and beta-galactosidase from Escherichia coli as selecting antigen, we generated three natural IgM mAb to HIV-1 and a natural IgM mAb to beta-galactosidase. The three HIV-1-selected antibodies (mAb102, mAb103, and mAb104) were polyreactive. They bound with different affinities (K(d) = 10(-6) to 10(-8) M) to the HIV-1 envelope gp160, the p24 core protein, and the p66 reverse transcriptase, but not to the 120 glycosilated env protein. They also bound to beta-galactosidase (K(d) approximately 10(-7) M), tetanus toxoid, and various self antigens. In contrast, the natural mAb selected for binding to beta-galactosidase (mAb207.F1) was monoreactive, in that it bound with a high affinity (K(d) < 10(-8) M) to this antigen, but to none of the other antigens tested, including HIV-1. Structural analysis of the V(H) and V(L) segments revealed that the natural mAb utilized three segments of the V(H)IV gene family and one of the V(H)III family, in conjunction with V(L) segments of the V(lambda)I, V(lambda)II, V(lambda)III, or V(chi)IV subgroups. In addition, the natural mAb V(H) and V(L) segments were in unmutated or virtually unmutated (germline) configuration, including those of the monoreactive mAb207.F1 to beta-galactosidase, and were identical or closely related to those utilized by specific autoantibodies or specific antibodies to viral and/or bacterial pathogens. Thus, the present data show that both polyreactive and monoreactive natural antibodies to foreign antigen can be isolated from the normal human B cell repertoire. They also suggest that the V(H) and V(L) segments of not only polyreactive but also monoreactive natural antibodies can be encoded in unmutated or minimally mutated genes, and possibly provide the templates for the specific high affinity antibodies elicited by self or foreign antigens. C1 NYU,SCH MED,DEPT PATHOL,MSB 599,550 1ST AVE,NEW YORK,NY 10016. NYU,SCH MED,KAPLAN COMPREHENS CANC CTR,NEW YORK,NY 10016. NIDR,ORAL MED LAB,BETHESDA,MD 20892. RI Casali, Paolo/F-6579-2010 FU NCI NIH HHS [P30 CA016087, CA-16087]; NIAMS NIH HHS [AR-40908, R01 AR040908] NR 88 TC 48 Z9 48 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD DEC PY 1993 VL 5 IS 12 BP 1523 EP 1533 DI 10.1093/intimm/5.12.1523 PG 11 WC Immunology SC Immunology GA MP959 UT WOS:A1993MP95900004 PM 8312222 ER PT J AU FONTVIEILLE, AM FERRARO, RT RISING, R LARSON, DE RAVUSSIN, E AF FONTVIEILLE, AM FERRARO, RT RISING, R LARSON, DE RAVUSSIN, E TI ENERGY-COST OF AROUSAL - EFFECT OF SEX, RACE AND OBESITY SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE ENERGY COST OF AROUSAL; BASAL METABOLIC RATE; SLEEPING METABOLIC RATE; INDIRECT CALORIMETRY; BODY COMPOSITION; SYMPATHETIC NERVOUS SYSTEM ID DEPENDENT DIABETES-MELLITUS; METABOLIC-RATE; PIMA-INDIANS; EXPENDITURE; PLASMA; THERMOGENESIS; BALANCE; HUMANS; WOMEN; DIET AB The basal (BMR) to sleeping metabolic rate (SMR) ratio might represent an estimate of the activation of the nervous system (central/sympathetic) from sleeping to basal state. Since this activation might be influenced by the degree of obesity, and might be different between sexes, we retrospectively analysed energy expenditure data collected for a large number of subjects. Twenty-four hour energy expenditure (24EE), BMR and SMR were measured in a respiratory chamber in 122 Caucasians (63 males/59 females, 32 +/- 1 0 years, 94 +/- 33 kg, 29 +/- 11% fat) (means +/- s.d.) and in 123 Pima Indians (68 males/55 females, 29 +/- 7 years, 100 +/- 25 kg, 34 +/- 9% fat). The BMR/SMR ratio varied greatly between individuals (1.05 +/- 0.08; range 0.87-1.34). In Pima Indians, BMR/SMR was inversely correlated to both fat mass (r = -0.26; P < 0.01) and BMI (r = -0.22; P < 0.05), whereas, in Caucasians, BMR/SMR was inversely correlated to waist/thigh circumference ratio (r = -0.28; P < 0.01). On average, the BMR/SMR was higher in Pima Indians than in Caucasians (1.06 +/- 0.08 vs. 1.03 +/- 0.07, P < 0.01) and higher in Pima Indian males than in Pima Indian females (1.08 +/- 0.09 vs. 1.04 +/- 0.06, P < 0.05). Studies are needed to investigate whether these differences in the increase in energy expenditure from the sleeping to the basal state are related to differences in the activation of the nervous system and/or to other metabolic factors. C1 NIDDKD,CLIN DIABET & NUTR SECT,4212 N 16TH ST,ROOM 541,PHOENIX,AZ 85016. NR 35 TC 10 Z9 10 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD DEC PY 1993 VL 17 IS 12 BP 705 EP 709 PG 5 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA MM087 UT WOS:A1993MM08700006 PM 8118475 ER PT J AU RAVUSSIN, E SWINBURN, BA AF RAVUSSIN, E SWINBURN, BA TI METABOLIC PREDICTORS OF OBESITY - CROSS-SECTIONAL VERSUS LONGITUDINAL DATA SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article; Proceedings Paper CT International Symposium on Regulation of Energy Expenditure and Circulation in Response to Nutrients CY MAY 25-27, 1993 CL COPENHAGEN, DENMARK DE BODY WEIGHT; METABOLIC RATE; SPONTANEOUS PHYSICAL ACTIVITY; RESPIRATORY QUOTIENT; INSULIN SENSITIVITY ID PIMA-INDIANS; WEIGHT-GAIN; BODY-WEIGHT; PATHOGENESIS; OXIDATION; RATIO; FAT AB In prospective studies in Pima Indians, four metabolic parameters, which are known to have a familial component, have been found to predict weight gain. These are: (i) low relative resting metabolic rate (RMR, relative to the average predicted rate for body size), (ii) low level of spontaneous physical activity (SPA), (iii) high 24 h respiratory quotient (RQ) and (iv) high insulin sensitivity (IS). Cross-sectional studies show that all four parameters correlate with body size: RMR vs. fat-free mass (FFM), r=0.87, P <0.0001; energy cost of SPA vs. weight, r=0.69, P <0.001; RQ vs. body fat, r=-0.23, P <0.05; IS vs. weight, r=-0.38, P <0.001. When these parameters are adjusted for differences in body size, then the initial value predicts the rate of change in body weight over the subsequent years: RMR (adjusted for FFM, fat mass, age and sex), r=-0.39, P <0.001; SPA, r=-0.35, P <0.005 (males); RQ (adjusted for fat mass), r=0.24, P <0.01; IS (adjusted for weight), r=0.34, P <0.0001. After gaining weight, the original deviation from the value predicted on the basis of the population (e.g. low relative RMR, high RQ and high IS) tends to diminish, suggesting a progressively decreasing physiological drive for further body weight gain. Thus, the high RMR, high energy cost of SPA, low Po and low IS seen in obesity may act to limit additional weight gain. C1 UNIV AUCKLAND,SCH MED,DEPT COMMUNITY HLTH,AUCKLAND,NEW ZEALAND. RP RAVUSSIN, E (reprint author), NIDDKD,CLIN DIABET & NUTR SECT,4212 N 16TH ST,SUITE 541,PHOENIX,AZ 85016, USA. NR 16 TC 78 Z9 79 U1 1 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD DEC PY 1993 VL 17 SU 3 BP S28 EP S31 PG 4 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA MN027 UT WOS:A1993MN02700009 PM 8124397 ER PT J AU SUZUKI, H ZHANG, X SOBEL, ME KONDOH, N PAPAS, TS BHAT, NK AF SUZUKI, H ZHANG, X SOBEL, ME KONDOH, N PAPAS, TS BHAT, NK TI EXPRESSION AND REGULATION OF THE 67-KDA LAMININ-BINDING PROTEIN AND ITS PRECURSOR GENE IN LYMPHOID-CELLS SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE CELL CYCLE; SIGNAL TRANSDUCTION; PROTEIN KINASE-C; PHORBOL ESTERS ID RECEPTOR MESSENGER-RNA; T-CELLS; EMBRYONIC RETINA; CARCINOMA-CELLS; ETS GENES; DIFFERENTIATION; CANCER; ADHESION; ANTIGEN; ENDOTHELIUM AB The 67-kDa laminin-binding protein is a non-integrin laminin-binding protein that mediates cancer cell adhesion and migration. The expression of the 67-kDa laminin-binding protein and of its putative precursor, a 37-kDa polypeptide, was studied in peripheral T-cells and T-lymphoma cell lines. Immunofluorescence experiments detected antigen in both the cytosol and on the cell membrane. On immunoblots of T-cell protein extracts, both the 37-kDa precursor and the mature 67-kDa protein were present. The mRNA for the precursor was expressed in both immature and mature thymocytes. In three independent T-lymphoma cell lines, the mRNA levels were decreased after prolonged stimulation with phorbol esters. Since the latter directly activate protein kinase C, it appears that regulation of the 37-kDa precursor in T-cells may be mediated by the signal transduction cascade associated with protein kinase C activation. C1 NCI,MOLEC ONCOL LAB,POB B,FREDERICK,MD 21702. NCI,PATHOL LAB,MOLEC PATHOL SECT,BETHESDA,MD 20892. MED UNIV S CAROLINA,CTR MOLEC & STRUCT BIOL,CHARLESTON,SC 29425. MED UNIV S CAROLINA,HOLLINGS CANC CTR,CHARLESTON,SC 29425. FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702. NR 57 TC 3 Z9 3 U1 0 U2 2 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD DEC PY 1993 VL 3 IS 6 BP 1049 EP 1056 PG 8 WC Oncology SC Oncology GA MG825 UT WOS:A1993MG82500004 PM 21573471 ER PT J AU BAIBAKOV, BA FRANK, GA MARGOLIS, LB SKULACHEV, VP AF BAIBAKOV, BA FRANK, GA MARGOLIS, LB SKULACHEV, VP TI ANTITUMOR EFFECT OF K+/H+-ANTIPORTER NIGERICIN ON HUMAN LUNG-CARCINOMA GROWN IN IN-VIVO-LIKE HISTOCULTURES SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE HISTOCULTURES; ANTIPORTER; LUNG TUMOR ID CYTOPLASMIC PH; DNA-SYNTHESIS AB Small shifts of intracellular pH (pH(i)) play a crucial role in many cellular functions, in particular progression through the cell cycle. We present results demonstrating that in the majority of cases, nigericin shows cytostatic effect on tumor cells in the in vivo-like 3-dimensional histocultures of human lung tissues while the normal tissue remains morphologically intact. C1 NIH,BLDG 10,ROOM 6C101,BETHESDA,MD 20894. HERZEN ONCOL INST,MOSCOW 125284,RUSSIA. MOSCOW MV LOMONOSOV STATE UNIV,AN BELOZERSKY INST PHYSICOCHEM BIOL,MOSCOW 119899,RUSSIA. RI Skulachev, Vladimir/J-4164-2012 OI Skulachev, Vladimir/0000-0003-4886-2243 NR 7 TC 1 Z9 1 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD DEC PY 1993 VL 3 IS 6 BP 1127 EP 1129 PG 3 WC Oncology SC Oncology GA MG825 UT WOS:A1993MG82500016 PM 21573483 ER PT J AU ATTILA, M SALVADORI, S BALBONI, G BRYANT, SD LAZARUS, LH AF ATTILA, M SALVADORI, S BALBONI, G BRYANT, SD LAZARUS, LH TI SYNTHESIS AND RECEPTOR-BINDING ANALYSIS OF DERMORPHIN HEPTA-PEPTIDE, HEXA-PEPTIDE AND PENTAPEPTIDE ANALOGS - EVIDENCE FOR ONE-SITE AND 2-SITE BINDING MODELS FOR THE MU-OPIOID RECEPTOR SO INTERNATIONAL JOURNAL OF PEPTIDE AND PROTEIN RESEARCH LA English DT Article DE DERMORPHIN; HILL COEFFICIENTS; MULTISITE ANALYSES; PEPTIDE SYNTHESIS; RECEPTOR BINDING ID PHYLLOMEDUSA-BICOLOR; BIOLOGICAL-ACTIVITIES; SHORTER HOMOLOGS; OPIATE RECEPTORS; AMPHIBIAN SKIN; HIGH-AFFINITY; DELTORPHIN-I; RAT; SELECTIVITY; IDENTIFICATION AB Sixteen dermorphin analogues were synthesized and characterized for mu- and delta-opioid receptor binding properties using [H-3]DAGO and [H-3]DPDPE, respectively. The analogues included the following: substitutions at position 4 and/or the C-terminal residue; deletions of Gly4 or Pro6-Ser7; inclusion of Z or an acetyl group on the epsilon-amino group of Lys7; and the presence of either a C-terminal amide or free acid group. Two peptides, [LyS7-OH]- and [LyS7-NH2]dermorphin, had mu-affinities (K(i)mu = 0.15-0.13 nm) and mu-selectivities (K(i)delta/K(i)mu = 1158-1482) higher than dermorphin (K(i)mu = 0.28 nm; K(i)delta/K(i)mu = 295) and best fitted a one-site binding model similar to dermorphin. Significantly better (P < 0.0001) fits to a two-site binding model vs. a one-site model were observed with four dermorphin analogues: [Lys(Z)7-OH]heptapeptide, [des-Gly4(Tyr4,Pro5,Asn6-OH)] hexapeptide and two pentapeptides, [Tyr5-NH2] and [Trp4,Asn5-OH]. Our data revealed a complex binding pattern for dermorphin analogues to brain mu-receptors in which Hill coefficients less than 0.85 generally suggest heterogeneity of mu-receptors; however, only detailed analyses of the data derived from the non-linear regression fits for one- or two-components gave evidence for the possible existence of two separate [H-3]DAGO binding sites. Eight of our dermorphin analogues had significantly better fits for a two-site model (P < 0.05), but only four seemed to have two distinct K(i) values (P < 0.000 1). (C) Munksgaard 1993. C1 NIEHS,INTEGRAT BIOL LAB,PEPTIDE NEUROCHEM SECT,POB 12233,RES TRIANGLE PK,NC 27709. UNIV FINLAND,DEPT PHARMACOL & TOXICOL,DIV PULM,HELSINKI,FINLAND. UNIV FERRARA,DEPT PHARMACEUT SCI,I-44100 FERRARA,ITALY. NR 38 TC 17 Z9 17 U1 0 U2 4 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0367-8377 J9 INT J PEPT PROT RES JI Int. J. Pept. Protein Res. PD DEC PY 1993 VL 42 IS 6 BP 550 EP 559 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MK199 UT WOS:A1993MK19900008 PM 7905867 ER PT J AU BOUZAS, EA MASTORAKOS, G FRIEDMAN, TC SCOTT, MH CHROUSOS, GP KAISERKUPFER, MI AF BOUZAS, EA MASTORAKOS, G FRIEDMAN, TC SCOTT, MH CHROUSOS, GP KAISERKUPFER, MI TI POSTERIOR SUBCAPSULAR CATARACT IN ENDOGENOUS CUSHING SYNDROME - AN UNCOMMON MANIFESTATION SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE POSTERIOR SUBCAPSULAR CATARACT; STEROID-INDUCED CATARACT; CUSHING SYNDROME; ENDOGENOUS HYPERCORTISOLISM AB Purpose. Posterior subcapsular cataract is a well-known complication of longstanding glucocorticoid therapy (exogenous Cushing syndrome). The purpose of this study was to examine the effect of chronic endogenous hypercortisolism (endogenous Cushing syndrome) on the human lens. Methods. Sixty consecutive patients (8 to 67 years of age, 46 females, 14 males) with endogenous Cushing syndrome were studied. The exposure to cortisol was estimated based on the duration of the disease and measurements of the 24-hour urine free cortisol excretion. Complete ocular examination included biomicroscopy of the lens after dilation. Results. Duration from the onset of endogenous Cushing syndrome ranged from 1 to 20 years (mean +/- SD, 5.5 +/- 3.7). Urine free cortisol excretion ranged from 250 to 3065 mug/24 hr (mean +/- SD, 693 +/- 547; normal values, 20 to 90 mug/24 hr). Only two of the 60 patients (3.3%) had posterior subcapsular cataract. This low prevalence contrasts to the high prevalence attributed to glucocorticoid therapy with grossly equivalent total dosage of glucocorticoids. Conclusion. It was concluded that posterior subcapsular cataract is an infrequent complication of endogenous hypercortisolism compared to exogenous Cushing syndrome. Because the total exposure to endogenous glucocorticoids was not lower than that of exogenous glucocorticoid therapy, a potential explanation for this difference might be the exposure of the lens to the natural (cortisol) rather than a synthetic glucocorticoid or pharmacokinetic differences of glucocorticoids between the two forms of Cushing syndrome. C1 NEI,OPHTHALM GENET & CLIN SERV BRANCH,9000 ROCKVILLE PIKE,BETHESDA,MD 20842. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD 20892. NR 13 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD DEC PY 1993 VL 34 IS 13 BP 3497 EP 3500 PG 4 WC Ophthalmology SC Ophthalmology GA MN579 UT WOS:A1993MN57900003 PM 8258505 ER PT J AU ASHRAF, F COGAN, DG KRUTH, HS AF ASHRAF, F COGAN, DG KRUTH, HS TI APOLIPOPROTEIN-A-I AND B-DISTRIBUTION IN THE HUMAN CORNEA SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE CORNEA; APOLIPOPROTEINS; LIPID; CHOLESTEROL; CORNEAL ARCUS; IMMUNOHISTOCHEMISTRY; LDL; HDL ID LIPID DEPOSITION; ARCUS FORMATION; ATHEROSCLEROSIS; PATHOGENESIS; METABOLISM; DISORDERS AB Purpose. To determine the presence and localization of apolipoprotein A-I, a marker for high density lipoprotein, and apolipoprotein B, a marker for low density lipoprotein, in human cornea; to examine the relationship of these lipoprotein markers with areas of lipid accumulation in the cornea. Methods. A-I and B apolipoproteins were localized in frozen sections of human corneas with specific monoclonal antibodies using avidin-biotin immunoperoxidase labelling. Corneal lipid was colocalized with apolipoproteins by oil red 0 staining of immunostained sections. Results. Staining data showed that apolipoprotein B and lipid accumulated in the extracellular spaces of peripheral corneal stroma. However, their distributions were not coincident. The posterior region of peripheral corneal stroma (including Descemet's membrane) often contained lipid without immunodetectable apolipoprotein B. Unexpectedly, apolipoprotein A-I was associated with many keratocytes throughout the cornea in addition to an extracellular distribution heaviest in peripheral cornea. Conclusions. Lipid deposits lacking apolipoprotein B in peripheral cornea suggest that if accumulated corneal arcus lipid is derived from extracellular deposition of plasma low density lipoprotein, the low density lipoprotein is altered such that it looses its immunoreactive apolipoprotein B. The unexpected association of apolipoprotein A-I with keratocytes suggests that these cells are either taking up or synthesizing a protein sharing an immunoreactive epitope with apolipoprotein A-I. C1 NEI,CLIN BRANCH,BETHESDA,MD 20892. NHLBI,EXPTL ATHEROSCLEROSIS SECT,BETHESDA,MD 20892. NR 13 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD DEC PY 1993 VL 34 IS 13 BP 3574 EP 3578 PG 5 WC Ophthalmology SC Ophthalmology GA MN579 UT WOS:A1993MN57900014 PM 8258515 ER PT J AU FERGUSON, JH DUBINSKY, M KIRSCH, PJ AF FERGUSON, JH DUBINSKY, M KIRSCH, PJ TI REIMBURSEMENT FOR UNPROVED THERAPIES - THE CASE OF THERMOGRAPHY - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 ADM CHILDREN & FAMILIES,WASHINGTON,DC. CUTLER & STANFIELD,WASHINGTON,DC. RP FERGUSON, JH (reprint author), NIH,BETHESDA,MD 20892, USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 1 PY 1993 VL 270 IS 21 BP 2558 EP 2559 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA MJ266 UT WOS:A1993MJ26600016 ER PT J AU LYKETSOS, CG HOOVER, DR GUCCIONE, M SENTERFITT, W DEW, MA WESCH, J VANRADEN, MJ TREISMAN, GJ MORGENSTERN, H AF LYKETSOS, CG HOOVER, DR GUCCIONE, M SENTERFITT, W DEW, MA WESCH, J VANRADEN, MJ TREISMAN, GJ MORGENSTERN, H TI DEPRESSIVE SYMPTOMS AS PREDICTORS OF MEDICAL OUTCOMES IN HIV-INFECTION SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; 500 PSYCHIATRIC OUTPATIENTS; MULTICENTER AIDS COHORT; FOLLOW-UP; LYMPHOCYTE SUBSETS; HOMOSEXUAL MEN; RISK; MORTALITY; CANCER; HEALTH AB Objective.-To ascertain whether depressive symptoms as determined by the Center for Epidemiologic Studies-Depression scale (CES-D) predict accelerated mortality and worse medical outcomes in patients infected with human immunodeficiency virus (HIV). Design.-Eight-year cohort study with semiannual follow-up. Setting.-Community volunteers. Participants.-A total of 1809 HIV-seropositive homosexual men without the acquired immunodeficiency syndrome (AIDS) who entered the Multicenter AIDS Cohort Study in 1984 or 1985. Eight-year follow-up data were available on 75% of eligible participants. Outcome Measures.-Times to AIDS, death, and prophylactic treatment, and slopes describing the decline in CD4 count for each individual participant. Results.-Using a conventional definition of depression (CES-D greater-than-or-equal-to 16 at the first study visit), 21.3% of participants were classified as depressed. Depressed participants had lower CD4 counts and reported more AIDS-related symptoms. There were no significant differences between depressed and nondepressed participants on any of the outcome measures (P>.05 in all cases). In contrast, men reporting AIDS-related symptoms had shorter times to AIDS and to death even after adjusting for CD4 counts (P<.01). The analyses were repeated, with similar results, using different definitions of depression based on the CES-D. Conclusions.-We find no evidence that depressive symptoms independently prognosticate worse outcomes in HIV infection. Because of associations of depression with symptom reports, CD4 counts, and indicators of socioeconomic status, future studies of the relationship between depression and HIV outcome should consider these variables as confounders. C1 JOHNS HOPKINS UNIV, SCH MED, DEPT PSYCHIAT & BEHAV SCI, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT MENTAL HYG, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT EPIDEMIOL, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH PUBL HLTH, BALTIMORE, MD 21218 USA. UNIV CALIF LOS ANGELES, SCH PUBL HLTH, DEPT EPIDEMIOL, LOS ANGELES, CA USA. UNIV PITTSBURGH, SCH MED, DEPT PSYCHIAT, PITTSBURGH, PA 15261 USA. UNIV PITTSBURGH, SCH PUBL HLTH, DEPT EPIDEMIOL, PITTSBURGH, PA 15260 USA. NORTHWESTERN UNIV, HOWARD BROWN MEM CLIN, CHICAGO, IL 60611 USA. NIAID, BETHESDA, MD 20892 USA. FU NIAID NIH HHS [N01-AI-32535, N01-AI-72631, N01-AI-72634] NR 31 TC 195 Z9 199 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 1 PY 1993 VL 270 IS 21 BP 2563 EP 2567 DI 10.1001/jama.270.21.2563 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA MJ266 UT WOS:A1993MJ26600022 PM 7901432 ER PT J AU SANDE, MA CARPENTER, CCJ COBBS, CG HOLMES, KK SANFORD, JP AF SANDE, MA CARPENTER, CCJ COBBS, CG HOLMES, KK SANFORD, JP TI ANTIRETROVIRAL THERAPY FOR ADULT HIV-INFECTED PATIENTS - RECOMMENDATIONS FROM A STATE-OF-THE-ART CONFERENCE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; PLACEBO-CONTROLLED TRIAL; AIDS-RELATED COMPLEX; DOUBLE-BLIND; AZIDOTHYMIDINE AZT; ZIDOVUDINE; EFFICACY AB This document summarizes recommendations from a state-of-the-art conference convened to evaluate the role of nucleoside analogue reverse transcriptase inhibitors in the treatment of human immunodeficiency virus (HIV) infection. Data from controlled clinical trials of zidovudine, didanosine, and zalcitabine were reviewed by an expert panel, which then formulated guidelines to assist clinicians and HIV-infected patients in the use of these agents. Recommendations were framed in the context of clinical scenarios for patients with asymptomatic HIV infection who have not had prior antiretroviral therapy; those with signs and symptoms of HIV-related disease who have not received prior therapy; clinically stable patients who are tolerating initial zidovudine therapy; patients experiencing clinical progression while on zidovudine therapy; and those who are intolerant of antiretroviral therapy. The panel concluded that physicians need to integrate up-to-date scientific knowledge with other relevant needs to improve the care of HIV-infected patients. C1 DEPT VET AFFAIRS MED CTR,BIRMINGHAM,AL. NIAID,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94143. BROWN UNIV,SCH MED,DIV BIOL & MED,PROVIDENCE,RI 02912. UNIV WASHINGTON,CTR AIDS & SEXUALLY TRANSMITTED DIS,SEATTLE,WA 98195. UNIV TEXAS,DEPT INTERNAL MED,DALLAS,TX 75230. NR 31 TC 148 Z9 150 U1 1 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 DEC 1 PY 1993 VL 270 IS 21 BP 2583 EP 2589 DI 10.1001/jama.270.21.2583 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA MJ266 UT WOS:A1993MJ26600026 PM 7901434 ER PT J AU GELBOIN, HV AF GELBOIN, HV TI CYTOCHROME-P-450 - THE JAPANESE CONNECTION SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Article ID LIVER RP GELBOIN, HV (reprint author), NCI,DEPT HEALTH & HUMAN SERV,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE CANCER ASSOCIATION PI TOKYO PA EDITORIAL OFFICE 7TH FLOOR, JOHKOH BLDG 2-23-11, KOISHIKAWA, TOKYO 112, JAPAN SN 0910-5050 J9 JPN J CANCER RES JI Jpn. J. Cancer Res. PD DEC PY 1993 VL 84 IS 12 BP 1320 EP 1321 PG 2 WC Oncology SC Oncology GA MN951 UT WOS:A1993MN95100018 ER PT J AU AARONSON, SA AF AARONSON, SA TI GROWING FAMILIES OF FIBROBLAST GROWTH-FACTORS AND RECEPTORS SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Article ID TRANSFORMING GENE; STOMACH CANCERS; DNA; CELLS; HST; IDENTIFICATION; EXPRESSION; SEQUENCE RP AARONSON, SA (reprint author), NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE CANCER ASSOCIATION PI TOKYO PA EDITORIAL OFFICE 7TH FLOOR, JOHKOH BLDG 2-23-11, KOISHIKAWA, TOKYO 112, JAPAN SN 0910-5050 J9 JPN J CANCER RES JI Jpn. J. Cancer Res. PD DEC PY 1993 VL 84 IS 12 BP 1326 EP 1327 PG 2 WC Oncology SC Oncology GA MN951 UT WOS:A1993MN95100021 ER PT J AU HARRIS, CC AF HARRIS, CC TI MULTISTEP CARCINOGENESIS SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Article ID HUMAN HEPATOCELLULAR CARCINOMAS; P53 GENE; MUTATION RP HARRIS, CC (reprint author), NCI,DIV CANC ETIOL,HUMAN CARCINOGENSIS,BETHESDA,MD 20892, USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE CANCER ASSOCIATION PI TOKYO PA EDITORIAL OFFICE 7TH FLOOR, JOHKOH BLDG 2-23-11, KOISHIKAWA, TOKYO 112, JAPAN SN 0910-5050 J9 JPN J CANCER RES JI Jpn. J. Cancer Res. PD DEC PY 1993 VL 84 IS 12 BP 1330 EP 1331 PG 2 WC Oncology SC Oncology GA MN951 UT WOS:A1993MN95100023 ER PT J AU PASTAN, I AF PASTAN, I TI C-ERBB-2 AND HUMAN CANCER SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-RECEPTOR; HUMAN CARCINOMA-CELLS; HUMAN-BREAST-CANCER; LONG-TERM SURVIVAL; NEU ONCOGENE; MONOCLONAL-ANTIBODY; GENE; PROTEIN; AMPLIFICATION; PROTOONCOGENE RP PASTAN, I (reprint author), NCI,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 29 TC 1 Z9 1 U1 0 U2 0 PU JAPANESE CANCER ASSOCIATION PI TOKYO PA EDITORIAL OFFICE 7TH FLOOR, JOHKOH BLDG 2-23-11, KOISHIKAWA, TOKYO 112, JAPAN SN 0910-5050 J9 JPN J CANCER RES JI Jpn. J. Cancer Res. PD DEC PY 1993 VL 84 IS 12 BP 1336 EP 1337 PG 2 WC Oncology SC Oncology GA MN951 UT WOS:A1993MN95100026 ER PT J AU CHABNER, BA AF CHABNER, BA TI MULTIDRUG-RESISTANCE - MECHANISM AND THERAPY SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Note ID BLOOD-BRAIN-BARRIER; P-GLYCOPROTEIN; ACTINOMYCIN-D; HAMSTER-CELLS; MONOCLONAL-ANTIBODIES; CROSS-RESISTANCE; TUMOR-CELLS; GENE; VERAPAMIL; ADRIAMYCIN RP CHABNER, BA (reprint author), NCI,DIV CANC TREATMENT,BETHESDA,MD 20892, USA. NR 37 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE CANCER ASSOCIATION PI TOKYO PA EDITORIAL OFFICE 7TH FLOOR, JOHKOH BLDG 2-23-11, KOISHIKAWA, TOKYO 112, JAPAN SN 0910-5050 J9 JPN J CANCER RES JI Jpn. J. Cancer Res. PD DEC PY 1993 VL 84 IS 12 BP UR1 EP UR1 PG 1 WC Oncology SC Oncology GA MN951 UT WOS:A1993MN95100001 ER PT J AU RADKEYARROW, M NOTTELMANN, E BELMONT, B WELSH, JD AF RADKEYARROW, M NOTTELMANN, E BELMONT, B WELSH, JD TI AFFECTIVE INTERACTIONS OF DEPRESSED AND NONDEPRESSED MOTHERS AND THEIR CHILDREN SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article ID PSYCHOPATHOLOGY; SEVERITY; PARENTS AB The expressed affect of clinically depressed and nondepressed mothers as measured by the Schedule for Affective Disorders and Schizophrenia: Lifetime Version (SADS-L) and their children (1 1/2 to 3 1/2 years) was observed in seminatural situations. The objectives were to investigate how maternal depression enters into affective interactions between mother and child and how the affect patterns of mother and child are related. Forty-nine unipolar and 24 bipolar depressed mothers and 45 nondepressed mothers were observed on 2 days, 2 weeks apart, for a total of 5 h. Each minute was coded for the predominant affect of mother and child. Affects relevant to depression (anxious-sad, irritable-angry, downcast, pleasant, tender-affectionate) were coded. Depressed mothers expressed significantly more negative affect than did control mothers. Mothers' expressed affect and their self-reports of affect on days of observation were unrelated. Mother's and child's affects, measured on different days, were significantly correlated. Unipolar mothers and mothers severely depressed spent significantly more time in prolonged bouts of negative affect. There was significant synchrony between their bouts and the negative bouts of their daughters. Gender of child was related to mother's and child's affect, and to relations between mother's and child's affect. RP RADKEYARROW, M (reprint author), NIMH,15K,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 17 TC 65 Z9 68 U1 1 U2 7 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0091-0627 J9 J ABNORM CHILD PSYCH JI J. Abnorm. Child Psychol. PD DEC PY 1993 VL 21 IS 6 BP 683 EP 695 DI 10.1007/BF00916450 PG 13 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA MQ123 UT WOS:A1993MQ12300006 PM 8126320 ER PT J AU DADA, AJ OYEWOLE, F ONOFOWOKAN, R NASIDI, A HARRIS, B LEVIN, A DIAMONDSTONE, L QUINN, TC BLATTNER, WA AF DADA, AJ OYEWOLE, F ONOFOWOKAN, R NASIDI, A HARRIS, B LEVIN, A DIAMONDSTONE, L QUINN, TC BLATTNER, WA TI DEMOGRAPHIC CHARACTERISTICS OF RETROVIRAL INFECTIONS (HIV-1, HIV-2, AND HTLV-I) AMONG FEMALE PROFESSIONAL SEX WORKERS IN LAGOS, NIGERIA SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HUMAN IMMUNODEFICIENCY VIRUS TYPE-1 (HIV-1) AND TYPE-2 (HIV-2); HUMAN T-LYMPHOTROPIC VIRUS TYPE-I (HTLV-I); FEMALE PROSTITUTES ID IVORY-COAST; VIRUS; LEUKEMIA; TRANSMISSION; LYMPHOMA; AIDS AB In 1990/1991, 885 prostitutes residing in 11 of the 12 Local Government Areas (LGAs) of Lagos State, Nigeria, participated in a cross-sectional study to determine current seroprevalence of antibodies to human immunodeficiency virus type I (HIV-1) and type 2 (HIV-2), and human T-cell lymphotropic virus type I (HTLV-I). The overall prevalence of HIV-1 was 12.3%, of HIV-2, 2. 1 %, and of HTLV-I, 2.8%. HIV-1 seropositivity did not vary significantly by age, socioeconomic class, or nationality, but HIV-1 seroprevalence was significantly elevated for prostitutes resident in the Port area of Lagos which serves as a crossroads for international and national commerce (OR = 2.3; 95% CI = 1.1, 4.6). HIV-2 infection was significantly associated with low socioeconomic class (OR = 3.7; 95% CI = 1.2, 10.8) and non-Nigerian nationality (OR = 6.7; 95% CI = 2.5, 18.4). Prevalence of HTLV-1 infection increased significantly with age (OR = 2.3; 95% CI = 1.0, 5.3). The high seroprevalence of HIV-1 in this survey, compared with previous surveys reported in the last several years and the correlation between high prevalence and areas of international commerce suggest that HIV-1 is spreading in this area of Nigeria. Intensified prevention campaigns are needed to address this possible emerging epidemic. C1 NCI,VIRAL EPIDEMIOL BRANCH,6130 EXECUT BLVD N,EPN-434,ROCKVILLE,MD 20852. RES TRIANGLE INST,WASHINGTON,DC. FED MINIST HLTH,CENT PUBL HLTH LAB,LAGOS,NIGERIA. FED VACCINE PROD LAB,LAGOS,NIGERIA. RES TRIANGLE INST,LONDON,ENGLAND. FU NCI NIH HHS [N01-CP-95612, N01-CP-85603] NR 16 TC 20 Z9 21 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD DEC PY 1993 VL 6 IS 12 BP 1358 EP 1363 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA MM128 UT WOS:A1993MM12800013 PM 8254475 ER PT J AU ROUM, JH BUHL, R MCELVANEY, NG BOROK, Z CRYSTAL, RG AF ROUM, JH BUHL, R MCELVANEY, NG BOROK, Z CRYSTAL, RG TI SYSTEMIC DEFICIENCY OF GLUTATHIONE IN CYSTIC-FIBROSIS SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE REDUCED GLUTATHIONE; OXIDANTS; ALVEOLAR MACROPHAGE; NEUTROPHIL; LUNG EPITHELIUM; BRONCHOSCOPY; RESPIRATORY EPITHELIAL LINING FLUID ID TUMOR-NECROSIS-FACTOR; EPITHELIAL LINING FLUID; IDIOPATHIC PULMONARY FIBROSIS; RESPIRATORY-DISTRESS SYNDROME; OXIDATIVE STATE; PLASMA; CELLS; IDENTIFICATION; AEROSOL; TRACT AB Cystic fibrosis (CF), a disorder characterized by mutations of the CF transmembrane regulator gene, is characterized in the lung by chronic inflammation, leading to progressive damage to the airway epithelium, bronchiectasis, and chronic obstructive lung disease. One process contributing to the airway derangement is the chronic burden of oxidants released by inflammatory cells on the respiratory epithelial surface. With this background, we hypothesized that glutathione in respiratory epithelial lining fluid (ELF) in CF patients might be oxidized and/or diminished in amount compared with that in normal subjects. Recovery of ELF by bronchoalveolar lavage from young adults with CF (n = 21) and normal subjects (n = 25) demonstrated marked neutrophil-dominated inflammation in ELF in CF patients. As predicted, ELF in CF patients was characterized by a deficiency of glutathione (P < 0.001), but this was secondary to a reduction in reduced glutathione (P < 0.001), inasmuch as there were no differences in ELF levels of oxidized glutathione (P > 0.2). Unexpectedly, there was also a marked deficiency of reduced glutathione in plasma (P < 0.02); i.e., the glutathione ''deficiency'' observed in ELF in CF patients is not limited to the site of the inflammation but is systemic. Although the etiology of this generalized deficiency of extracellular glutathione is unknown, it is important in considering options for treating the concomitant and devastating lung pathology in this disorder. C1 NHLBI,PULM BRANCH,BETHESDA,MD 20892. RI McElvaney, Noel/A-6809-2010 NR 53 TC 262 Z9 264 U1 1 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD DEC PY 1993 VL 75 IS 6 BP 2419 EP 2424 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA MN705 UT WOS:A1993MN70500012 PM 8125859 ER PT J AU RUSSO, TA SINGH, G AF RUSSO, TA SINGH, G TI AN EXTRAINTESTINAL, PATHOGENIC ISOLATE OF ESCHERICHIA-COLI (04/K54/H5) CAN PRODUCE A GROUP-1 CAPSULE WHICH IS DIVERGENTLY REGULATED FROM ITS CONSTITUTIVELY PRODUCED GROUP-2, K54 CAPSULAR POLYSACCHARIDE SO JOURNAL OF BACTERIOLOGY LA English DT Article ID KLEBSIELLA-PNEUMONIAE; K1 CAPSULE; RCSA GENE; K-12; ANTIGEN; EXPRESSION; CLONING; BIOSYNTHESIS; RESISTANCE; O1-K20 AB We are studying an 04/K54/H5 Escherichia coli bacteremic isolate (CP9) as a model pathogen for extraintestinal infection. Its group 2, K54 capsular polysaccharide is an important virulence determinant and confers serum resistance. In this study the effect of the group 1 capsule regulators, RcsA, RcsB, and Lon protease, on the regulation of CP9's capsular polysaccharides was assessed. It was established that in the presence of multicopy rcsA or with disruption of ion, CP9 can be induced to produce a group 1 capsule. RcsA, RcsB, and Lon are present in this K54 background and regulate group 1 capsule expression in a fashion similar to that described for K-12 strains. Two independent group 2 capsule gene protein fusions (cl1.29::TnphoA and cl1.137::TnphoA) were used to evaluate the effects of these regulators on group 2 K54 capsule production. Disruption of ion resulted in 1.9-fold (TR293 [cl1.29::TnphoA lon-146]) and 3.4-fold (TR1373 [cl1.137::TnphoA lon-146]) decreases in fusion activity at 28 degrees C, relative to the baseline level. However, decreases in fusion activity at 42 degrees C were only 1.2- and 1.4-fold, respectively. Inactivation of both ion and rcsA or lon and rcsB restored fusion activity to baseline levels at 28 degrees C, but only a partial restoration of activity was seen at higher temperatures. To assess whether these differences in fusion activity reflected a functional change in capsule production, the effects of 80% normal human serum (NHS) were tested against CP9 and TR93 (lon-146). Since the group 2 K54 capsule protects against the bactericidal activity of 80% NHS, a decrease in its production results in an increase in serum sensitivity. Viable counts of CP9 increased 10-fold in 80% NHS over 3 h at 28 degrees C, as expected. In contrast to CP9, TR93 (lon-146) incurred a 10-fold loss in viability under the same conditions. The levels of RcsA are increased in TR93 (lon-146) as a consequence of lon disruption; therefore, these results in conjunction with the cl1::TnphoA protein fusion data establish RcsA as a negative regulator of the group 2 K54 capsular polysaccharide. Its action appears to be mediated through RcsB and is greatest at 28 degrees C but decreases at higher temperatures. Furthermore, these results also suggest the existence of another Lon-sensitive negative regulator of group 2 K54 capsule production, which is active at higher temperatures. RP RUSSO, TA (reprint author), NIAID,CLIN INVEST LAB,BACTERIAL PATHOGENESIS UNIT,BETHESDA,MD 20892, USA. NR 37 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 1993 VL 175 IS 23 BP 7617 EP 7623 PG 7 WC Microbiology SC Microbiology GA MH737 UT WOS:A1993MH73700012 PM 8244930 ER PT J AU KARLS, RK JIN, DJ DONOHUE, TJ AF KARLS, RK JIN, DJ DONOHUE, TJ TI TRANSCRIPTION PROPERTIES OF RNA-POLYMERASE HOLOENZYMES ISOLATED FROM THE PURPLE NONSULFUR BACTERIUM RHODOBACTER-SPHAEROIDES SO JOURNAL OF BACTERIOLOGY LA English DT Article ID HEAT-SHOCK PROMOTERS; ESCHERICHIA-COLI; PSEUDOMONAS-AERUGINOSA; NUCLEOTIDE-SEQUENCE; BIOSYNTHESIS GENE; DNA-SEQUENCES; SIGMA-SUBUNIT; PURIFICATION; CAPSULATUS; EXPRESSION AB We have been characterizing RNA polymerase holoenzymes from Rhodobacter sphaeroides. RNA polymerase purified from R. sphaeroides transcribed from promoters recognized by Escherichia coli E sigma(32) or E sigma(70) holoenzyme. Antisera to E. coli sigma(32) or sigma(70) indicated that related polypeptides of approximate to 37 kDa (sigma(37)) and 93 kDa (sigma(93)), respectively, are present in this preparation. Transcription of sigma(32)-dependent promoters was observed in a further fractionated R. sphaeroides holoenzyme containing the sigma(37) polypeptide, while a preparation enriched in sigma(93) transcribed sigma(70)-dependent promoters. To demonstrate further that the sigma(93) polypeptide functions like E. coli sigma(70), we obtained an R. sphaeroides E sigma(93) holoenzyme capable of transcription from sigma(70)-dependent promoters by combining sigma(93) with (i) an E sigma(37) fraction with diminished sigma(93) polypeptide content or (ii) E. coli core RNA polymerase. The generation of analogous DNase I footprints on the lacUV5 promoter by R. sphaeroides E sigma(93) and by E. coli E sigma(70) suggests that the overall structures of these two holoenzymes are similar. However, some differences in promoter specificity between R. sphaeroides E sigma(93) and E. coli E sigma(70) exist because transcription of an R. sphaeroides rRNA promoter was detected only with E sigma(93). C1 UNIV WISCONSIN, DEPT BACTERIOL, MADISON, WI 53706 USA. NCI, BETHESDA, MD 20892 USA. OI Donohue, Timothy/0000-0001-8738-2467 FU NIAID NIH HHS [AI19635]; NIGMS NIH HHS [GM07215, GM37509] NR 44 TC 26 Z9 26 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 1993 VL 175 IS 23 BP 7629 EP 7638 PG 10 WC Microbiology SC Microbiology GA MH737 UT WOS:A1993MH73700014 PM 8244932 ER PT J AU CLARK, AJ SHARMA, V BRENOWITZ, S CHU, CC SANDLER, S SATIN, L TEMPLIN, A BERGER, I COHEN, A AF CLARK, AJ SHARMA, V BRENOWITZ, S CHU, CC SANDLER, S SATIN, L TEMPLIN, A BERGER, I COHEN, A TI GENETIC AND MOLECULAR ANALYSES OF THE C-TERMINAL REGION OF THE RECE GENE FROM THE RAC PROPHAGE OF ESCHERICHIA-COLI K-12 REVEAL THE RECT GENE SO JOURNAL OF BACTERIOLOGY LA English DT Article ID TRANSPOSON-INDUCED MUTATIONS; EXONUCLEASE-VIII; BACTERIOPHAGE-LAMBDA; PLASMID RECOMBINATION; BETA-PROTEIN; INDIRECT SUPPRESSION; AFFECT EXPRESSION; PHYSICAL ANALYSIS; DNA; MUTANTS AB The nucleotide sequence of the C-terminal region of the recE gene of the Rac prophage of Escherichia coli K-12 reveals the presence of a partially overlapping reading frame we call recT. Deletion mutations show that recT is required for the RecE pathway of conjugational recombination. By cloning recT with a plasmid vector compatible with pBR322, we showed by cis-trans tests that the portion of the recE gene encoding ExoVIII DNA nuclease activity is also required for RecE pathway conjugational recombination. The recT gene can replace the redB gene of lambda for recA-independent plasmid recombination. A Tn10 insertion mutation previously thought to be in recE is located in recT and is renamed recT101::Tn10. Discrepancies between the molecular mass estimates of wild-type ExoVIII protein determined from mobility in sodium dodecyl sulfate-polyacryl-amide gel electrophoresis (SDS-PAGE) and calculated from the predicted amino acid sequence are discussed. The hypothesis that wild-type ExoVIII protein results from fusion of RecE and RecT proteins is disproved genetically, thus supporting a previous hypothesis that the discrepancies are due to abnormal protein mobility in SDS-PAGE. A computer-performed scan of the bacteriophage nucleotide sequence data base of GenBank revealed substantial similarity between most of recE and a 2.5-kb portion of the b2 region of lambda. This suggests interesting speculations concerning the evolutionary relationship of lambda and Rac prophages. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT MOLEC GENET,IL-91010 JERUSALEM,ISRAEL. RP CLARK, AJ (reprint author), UNIV CALIF BERKELEY,BARKER KOSHLAND ASU,DEPT MOLEC & CELL BIOL,BERKELEY,CA 94720, USA. FU PHS HHS [5371] NR 39 TC 38 Z9 42 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 1993 VL 175 IS 23 BP 7673 EP 7682 PG 10 WC Microbiology SC Microbiology GA MH737 UT WOS:A1993MH73700020 PM 8244937 ER PT J AU LOMBARDO, MJ MILLER, CG RUDD, KE AF LOMBARDO, MJ MILLER, CG RUDD, KE TI PHYSICAL MAPPING OF THE ESCHERICHIA-COLI PEPT AND POTABCD GENES SO JOURNAL OF BACTERIOLOGY LA English DT Note ID SALMONELLA-TYPHIMURIUM; PEPTIDASE-T; CHROMOSOME; MUTANTS; CLONING C1 UNIV ILLINOIS,DEPT MICROBIOL,URBANA,IL 61801. NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. FU NIAID NIH HHS [AI10333] NR 11 TC 8 Z9 9 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 1993 VL 175 IS 23 BP 7745 EP 7746 PG 2 WC Microbiology SC Microbiology GA MH737 UT WOS:A1993MH73700036 PM 8244951 ER PT J AU ABELES, A BRENDLER, T AUSTIN, S AF ABELES, A BRENDLER, T AUSTIN, S TI EVIDENCE FOR 2 LEVELS OF CONTROL OF P1 ORIR AND HOST ORIC REPLICATION ORIGINS BY DNA ADENINE METHYLATION SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI CHROMOSOME; PLASMID REPLICATION; DAM METHYLTRANSFERASE; GATC SITES; GENE; INVITRO; INITIATION; REGION; PURIFICATION; EXPRESSION AB A mutant mini-P1 plasmid with increased copy number can be established in Dam- strains of Escherichia coli, where mini-P1 plasmid replication is normally blocked. Comparison of this plasmid and a plasmid driven by the host oriC replication origin showed that both origins are subject to control by methylation at two different levels. First, both origins appear to be subject to negative regulation acting at the level of hemimethylation. This probably involves the sequestration of the hemimethylated DNA produced by replication, as has been previously described for oriC. Second, both origins show a positive requirement for adenine methylation for efficient function in vivo. This conclusion is supported by the behavior of the P1 origin in an improved in vitro replication system. In vitro, where sequestration of hemimethylated DNA is not expected to occur, the hemimethylated P1 origin DNA was fully functional as a template. However, the activity of fully unmethylated DNA was severely restricted in comparison with that of either of the methylated forms. This in vitro uncoupling of the two effects of origin methylation suggests that two separate mechanisms are involved. RP ABELES, A (reprint author), NCI,FREDERICK CANC RES & DEV CTR,CHROMOSOME BIOL LAB,FREDERICK,MD 21701, USA. FU NCI NIH HHS [N01-CO-74101] NR 40 TC 20 Z9 20 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 1993 VL 175 IS 24 BP 7801 EP 7807 PG 7 WC Microbiology SC Microbiology GA ML898 UT WOS:A1993ML89800007 PM 8253669 ER PT J AU COHEN, SP LEVY, SB FOULDS, J ROSNER, JL AF COHEN, SP LEVY, SB FOULDS, J ROSNER, JL TI SALICYLATE INDUCTION OF ANTIBIOTIC-RESISTANCE IN ESCHERICHIA-COLI - ACTIVATION OF THE MAR OPERON AND A MAR-INDEPENDENT PATHWAY SO JOURNAL OF BACTERIOLOGY LA English DT Article ID OUTER-MEMBRANE; OMPF PORIN; EXPRESSION; CHLORAMPHENICOL; TETRACYCLINE; GENE; ACCUMULATION; INHIBITION; SIGNAL; LOCUS AB Since the growth of wild-type Escherichia coli in salicylate results in a multiple antibiotic resistance phenotype similar to that of constitutive mutants (Mar) of the chromosomal mar locus, the effect of salicylate on the expression of the marRAB operon was investigated. The amount of RNA hybridizing with a mar-specific DNA probe was 5 to 10 times higher in wild-type cells grown with sodium salicylate (5.0 mM) than in untreated controls. Untreated Mar mutants had three to five times more mar-specific RNA than wild-type cells did. When a Mar mutant was treated with salicylate, a 30- to 50-fold increase of mar-specific RNA was seen. In wild-type cells bearing a mar promoter-lacZ fusion on the chromosome, salicylate increased beta-galactosidase activity by sixfold. Thus, salicylate induces transcription of the marRAB operon. Other inducers of phenotypic multiple antibiotic resistance, e.g., benzoate, salicyl alcohol, and acetaminophen, but not acetate, also increased transcription from the mar promoter but to a lesser extent than did salicylate. Both in wild-type and mar-deficient strains, growth in salicylate resulted in increased antibiotic resistance, decreased permeation of the outer membrane to cephaloridine, increased micF transcription, and decreased amounts of OmpF. However, the magnitude of these changes was generally greater in wild-type (mar-containing) cells. Thus, salicylate and other compounds can induce transcription of the mar operon and, presumably, give rise to multiple antibiotic resistance via this pathway. However, salicylate can also activate an unidentified, mar-independent pathway(s) which engenders multiple antibiotic resistance. C1 TUFTS UNIV,SCH MED,DEPT MOLEC BIOL & MICROBIOL,CTR ADAPTAT GENET & DRUG RESISTANCE,BOSTON,MA 02111. TUFTS UNIV,SCH MED,DEPT MED,BOSTON,MA 02111. NIDDKD,STRUCT BIOL LAB,BETHESDA,MD 20892. NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. FU NIAID NIH HHS [AI16756] NR 30 TC 205 Z9 210 U1 1 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 1993 VL 175 IS 24 BP 7856 EP 7862 PG 7 WC Microbiology SC Microbiology GA ML898 UT WOS:A1993ML89800014 PM 7504664 ER PT J AU GENTRY, DR HERNANDEZ, VJ NGUYEN, LH JENSEN, DB CASHEL, M AF GENTRY, DR HERNANDEZ, VJ NGUYEN, LH JENSEN, DB CASHEL, M TI SYNTHESIS OF THE STATIONARY-PHASE SIGMA-FACTOR SIGMA(S) IS POSITIVELY REGULATED BY PPGPP SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI; ALKALINE-PHOSPHATASE; GEARBOX PROMOTERS; KATF; TRANSCRIPTION; MUTANTS; GENE; 3'-DIPHOSPHATE; 5'-DIPHOSPHATE; MUTATIONS AB Strains of Escherichia coli which lack detectable guanosine 3',5'-bispyrophosphate (ppGpp) display a pleiotropic phenotype that in some respects resembles that of rpoS (katF) mutants. This led us to examine whether ppGpp is a positive regulator of sigma(s) synthesis. Sigma(s) is a stationary-phase-specific sigma factor that is encoded by the rpoS gene. We found that a ppGpp-deficient strain is defective in sigma(s) synthesis as cells enter stationary phase in a rich medium, as judged by immunoblots. Under more-defined conditions we found that the stimulation of sigma(s) synthesis following glucose, phosphate, or amino acid starvation of wild-type strains is greatly reduced in a strain lacking ppGpp. The failure of ppGpp-deficient strains to synthesize sigma(s) in response to these starvation regimens could indicate a general defect in gene expression rather than a specific dependence of rpoS expression on ppGpp. We therefore tested the effect of artificially elevated ppGpp levels on sigma(s) synthesis either with mutations that impair ppGpp decay or by gratuitously inducing ppGpp synthesis with a P(tac)=relA fusion. In both instances, we observed enhanced sigma(s) synthesis. Apparently, ppGpp can activate sigma(s) synthesis under conditions of nutrient sufficiency as well as during entry into stationary phase. This finding suggests that changes in ppGpp levels function both as a signal of imminent stationary phase and as a signal of perturbations in steady-state growth. C1 UNIV WISCONSIN,MCARDLE LAB CANC RES,MADISON,WI 53706. RP GENTRY, DR (reprint author), NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA07175, CA09135]; NIGMS NIH HHS [GM28575] NR 39 TC 338 Z9 346 U1 1 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 1993 VL 175 IS 24 BP 7982 EP 7989 PG 8 WC Microbiology SC Microbiology GA ML898 UT WOS:A1993ML89800030 PM 8253685 ER PT J AU NERURKAR, PV ANDERSON, LM SNYDERWINE, EG PARK, SS THORGEIRSSON, SS RICE, JM AF NERURKAR, PV ANDERSON, LM SNYDERWINE, EG PARK, SS THORGEIRSSON, SS RICE, JM TI SPECIFIC INDUCTION OF HEPATIC CYTOCHROME P4501A-2 IN C57BL/6 AND DBA/2 MICE TREATED WITH 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE (IQ) SO JOURNAL OF BIOCHEMICAL TOXICOLOGY LA English DT Article DE FOOD MUTAGENS; HETEROCYCLIC AROMATIC AMINES; IQ; P4501A-2 ID CARCINOGENIC AROMATIC-AMINES; RAT-LIVER; MUTAGENIC ACTIVATION; MESSENGER-RNA; MONOCLONAL-ANTIBODIES; HETEROCYCLIC AMINES; AH LOCUS; PYROLYSATE; FOOD; 3-METHYLCHOLANTHRENE AB The food mutagen/carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) is activated by cytochrome p4501a-2 via N-hydroxylation; various P450s may contribute to detoxification via ring hydroxylation. Alterations in P450 levels by IQ treatment might therefore influence its toxicity. To examine the role of Ah locus genotype on the biochemical effects of IQ, C57BL/6 (Ah(b)Ah(b); p450Ia-1/2 inducible) and DBA/2 (Ah(d)Ah(d), noninducible) mice of both sexes were given IQ at varying doses, with different vehicles and routes of administration. Livers taken after 24 hours were assessed for total cytochrome p450 and activities of ethoxyresorufin-O-deethylase (EROD, a p4501a-1 activity, inducible in Ah(b) mice), methoxyresorufin-O-demethylase MROD, a p4501a-2 (activity), and benzyloxyresorufin-O-dealkylase (BzROD, an activity of p4502b). There was little effect on total cytochrome p450, but all three enzyme activities were often induced, a maximum of 2.5-fold, in both sexes and in DBA/2 as well as C57BL/6 mice. However, Western immunoblot analysis with monoclonal antibodies demonstrated an increase only in p4501a-2 protein. p4501a-1 remained undetectable. A monoclonal antibody to p4502-b recognized one protein band in liver microsomes from males and two bands in female mice of both strains. Amounts of these proteins were not altered by IQ treatment. Thus, IQ specifically, if moderately, induces its activating enzyme, p4501a-2, in a process that was not clearly related to Ah responsiveness. C1 NCI,DIV CANC ETIOL,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. RP NERURKAR, PV (reprint author), NCI,DIV CANC ETIOL,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. NR 56 TC 8 Z9 8 U1 1 U2 1 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0887-2082 J9 J BIOCHEM TOXICOL JI J. Biochem. Toxicol. PD DEC PY 1993 VL 8 IS 4 BP 175 EP 186 DI 10.1002/jbt.2570080403 PG 12 WC Toxicology SC Toxicology GA MN958 UT WOS:A1993MN95800002 PM 8114061 ER PT J AU DYKES, DC FRIEDMAN, FK DYKES, SL MURPHY, RB BRANDTRAUF, PW PINCUS, MR AF DYKES, DC FRIEDMAN, FK DYKES, SL MURPHY, RB BRANDTRAUF, PW PINCUS, MR TI MOLECULAR-DYNAMICS OF THE H-RAS GENE-ENCODED P21 PROTEIN - IDENTIFICATION OF FLEXIBLE REGIONS AND POSSIBLE EFFECTOR DOMAINS SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article ID XENOPUS OOCYTES; KINASE-C; ONCOGENE; TRANSFORMATION; BINDING; GDP; MICROINJECTION; P21-PROTEIN; ACTIVATION; ANTIBODIES AB We previously reported a complete computer-based three-dimensional structure for residues 1-171 of the Gly 12-containing ras-gene-encoded p21 protein complexed with GDP. This structure was subsequently shown to closely agree with a high-resolution x-ray crystallographic structure of p21. In this communication, we report a molecular dynamics simulation of the modelled structure in an explicit shell of water molecules to identify domains within the protein that are unusually flexible. These domains represent regions which are most likely to C1 SUNY HLTH SCI CTR,DEPT PATHOL,SYRACUSE,NY 13210. SUNY HLTH SCI CTR,DEPT BIOCHEM & MOLEC BIOL,SYRACUSE,NY 13210. NIH,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. SUNY HLTH SCI CTR,DEPT ANAT & CELL BIOL,SYRACUSE,NY 13210. NYU,DEPT CHEM,NEW YORK,NY 10003. COLUMBIA UNIV COLL PHYS & SURG,DEPT MED,DIV ENVIRONM SCI,NEW YORK,NY 10032. RI Friedman, Fred/D-4208-2016 FU NCI NIH HHS [CA 42500] NR 41 TC 14 Z9 14 U1 0 U2 1 PU ADENINE PRESS INC PI GUILDERLAND PA PO BOX 355/340, GUILDERLAND, NY 12084 SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD DEC PY 1993 VL 11 IS 3 BP 443 EP 458 PG 16 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MQ368 UT WOS:A1993MQ36800001 PM 8129867 ER PT J AU MCGOWAN, J REDFORD, M AF MCGOWAN, J REDFORD, M TI PROCEEDINGS OF THE WORKSHOP ON OSTEOPOROSIS AND ORAL BONE LOSS LEESBURG, VIRGINIA AUGUST 1992 - INTRODUCTION SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Editorial Material C1 NIDR,BETHESDA,MD 20892. RP MCGOWAN, J (reprint author), NIAMSD,BETHESDA,MD, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD DEC PY 1993 VL 8 SU 2 BP S449 EP S449 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MQ496 UT WOS:A1993MQ49600001 ER PT J AU REDFORD, M MCGOWAN, J AF REDFORD, M MCGOWAN, J TI PROCEEDINGS OF THE WORKSHOP ON OSTEOPOROSIS AND ORAL BONE LOSS LEESBURG, VIRGINIA AUGUST 1992 - EXECUTIVE SUMMARY AND RESEARCH RECOMMENDATIONS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Editorial Material C1 NIDR,BETHESDA,MD 20892. RP REDFORD, M (reprint author), NIAMSD,BETHESDA,MD, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD DEC PY 1993 VL 8 SU 2 BP S451 EP S453 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MQ496 UT WOS:A1993MQ49600002 ER PT J AU ROBEY, PG FEDARKO, NS HEFFERAN, TE BIANCO, P VETTER, UK GRZESIK, W FRIEDENSTEIN, A VANDERPLUIJM, G MINTZ, KP YOUNG, MF KERR, JM IBARAKI, K HEEGAARD, AM AF ROBEY, PG FEDARKO, NS HEFFERAN, TE BIANCO, P VETTER, UK GRZESIK, W FRIEDENSTEIN, A VANDERPLUIJM, G MINTZ, KP YOUNG, MF KERR, JM IBARAKI, K HEEGAARD, AM TI STRUCTURE AND MOLECULAR REGULATION OF BONE-MATRIX PROTEINS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT NIH Workshop on Osteoporosis and Oral Bone Loss CY AUG, 1992 CL LEESBURG, VA SP NIH, NIDR, NIAMSD, NIH, OFF RES WOMENS HLTH ID GLA PROTEIN; OSTEONECTIN; SIALOPROTEIN; GLYCOPROTEIN; OSTEOPONTIN; EXPRESSION; SEQUENCE; HOMOLOGY; SPARC AB The organic matrix of bone contains several protein families, including collagens, proteoglycans, and glycoproteins, all of which may be extensively modified by posttranslational events, such as phosphorylation and sulfation. Many of the glycoproteins contain Arg-Gly-Asp (RGD), the integrin-binding sequence, within their structure, whereas other constituent proteins contain gamma-carboxyglutamic acid. The deposition of bone matrix by cells in the osteoblastic lineage is regulated by extrinsic factors, such as systemic and local growth factors and physical forces, and factors that are intrinsic to the cell, such as position in the cell cycle, maturational stage, and developmental age of the donor. Recent studies of several bone matrix gene promoters have identified cis- and trans-acting elements that are responsible for gene activity, although the precise sequence of regulatory events is not known. Development of in vitro assays, coupled with studies of the appearance of these proteins during development in vivo, provides insight into the functions of these proteins during the various stages of bone metabolism. Potential roles for these proteins include proliferation and maturation of stem cells, formation of matrix scaffolding elaborated by bone-forming cells, modeling, and remodeling. Changes in the functional properties of the extracellular matrix may be involved in a variety of disease processes, including osteoporosis and oral bone loss. RP ROBEY, PG (reprint author), NIDR,BONE RES BRANCH,SKELETAL BIOL SECT,BLDG 30,ROOM 106,BETHESDA,MD 20892, USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 34 TC 42 Z9 44 U1 1 U2 4 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD DEC PY 1993 VL 8 SU 2 BP S483 EP S487 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MQ496 UT WOS:A1993MQ49600008 PM 8122516 ER PT J AU EVANS, CH AF EVANS, CH TI CYTOKINES - MOLECULAR KEYS TO HOMEOSTASIS, DEVELOPMENT, AND PATHOPHYSIOLOGY SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Editorial Material DE CYTOKINE; LYMPHOKINE; INTERFERON ID LEUKOREGULIN AB Identification and definition of the role and diversity of action of cytokines, the regulatory proteins including lymphokines, monokines, interleukins, interferons, and a variety of other growth factors produced by virtually every nucleated cell into the body and having pleiotropic regulatory effects on hematopoietic and many other cell types [Thompson, 1991], are in the forefront of biomedical research. The explosive development of cytokine research is reflected by the inclusion of ''cytokine,'' first introduced as a term in 1974 to recognize that lymphokines could be produced by other than lymphoid cells in 4,267 biomedical articles published by the end of 1992. From the initial reference to cytokines in 1974 to inclusion in 45 articles in 1985, the doubling of citations each succeeding year, together with 45% of all the citations since 1974 occurring in 1992 alone, attests to the continued rapid expansion of this area of biological research. The important roles of cytokines in many physiological processes and pathophysiological conditions, although largely descriptive in nature, were recognized during the early development of this field of investigation [Balkwill and Burke, 1989; Cohen et al., 1974]. Current and future directions, as highlighted by the series of Prospect articles featuring areas as diverse as embryologic, extracellular matrix, bone, hematologic, and neurologic development and function as well as in the organism's response to foreign organisms in this issue of the Journal, are focused on broadening our understanding of the positive and negative influence of cytokines in normal and abnormal differentiation and development and on the molecular pathways underlying cytokine action. The broad areas of cellular biochemistry represented by the Prospects, moreover, emphasize the synthesis and convergence of cytokine research towards an understanding of the critical controls in development and homeostasis. (C) 1993 Wiley-Liss, Inc.* RP EVANS, CH (reprint author), NIH,BIOL LAB,BETHESDA,MD 20892, USA. NR 17 TC 11 Z9 12 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD DEC PY 1993 VL 53 IS 4 BP 277 EP 279 DI 10.1002/jcb.240530402 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ML654 UT WOS:A1993ML65400001 PM 8300743 ER PT J AU SHEIKH, MS SHAO, ZM CHEN, JC HUSSAIN, A JETTEN, AM FONTANA, JA AF SHEIKH, MS SHAO, ZM CHEN, JC HUSSAIN, A JETTEN, AM FONTANA, JA TI ESTROGEN RECEPTOR-NEGATIVE BREAST-CANCER CELLS TRANSFECTED WITH THE ESTROGEN-RECEPTOR EXHIBIT INCREASED RAR-ALPHA GENE-EXPRESSION AND SENSITIVITY TO GROWTH-INHIBITION BY RETINOIC ACID SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE TRANSFECTION; CAT ASSAYS; GENE EXPRESSION ID RESPONSE ELEMENT; PROLIFERATION; PROMOTER; LINES; DIFFERENTIATION; ANTAGONISM AB We and others have shown previously that retinoic acid (RA) selectively inhibits the growth of estrogen receptor (ER)-positive human breast carcinoma (HBC) cells and ER-negative cells are refractory to RA inhibition of growth. The ER-negative cells inherently express lower levels of RARalpha and retinoic acid response element (RARE)-mediated RA-induced CAT activity. In this study we report that when ER-negative MDA-MB-231 cells were transfected with the ER gene they not only expressed higher levels of RARalpha and RARE-mediated RA-induced CAT gene expression, but their growth was now inhibited by RA. Estrogen enhanced RARalpha gene expression not only in established ER-positive cell lines but also in ER-transfected MDA-MB-231 cells. The estrogen effect appears to be direct and at the gene transcription level since it did not alter the stability of RARalpha mRNA and cycloheximide failed to block estrogen-mediated enhancement of RARalpha gene expression. Our data strongly suggest that ER-mediated enhancement of RARalpha levels plays an important role in RA inhibition of HBC growth. In addition, we also report here that HBC cells appear to express a unique isoform(s) of RARalpha which was detected only when the full-length RARalpha cDNA was used as a probe; the RARalpha1 and RARalpha2 specific probes failed to hybridize with the HBC specific RARalpha message. C1 UNIV MARYLAND,SCH MED,DEPT MED,DIV ONCOL,BALTIMORE,MD 21201. NIEHS,PULM PATHOBIOL LAB,CELL BIOL SECT,RES TRIANGLE PK,NC 27709. VET ADM MED CTR,BALTIMORE,MD 21201. UNIV MARYLAND,CTR CANC,COLL PK,MD 20742. OI Jetten, Anton/0000-0003-0954-4445; Fontana, Joseph/0000-0003-3829-3358 NR 27 TC 59 Z9 60 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD DEC PY 1993 VL 53 IS 4 BP 394 EP 404 DI 10.1002/jcb.240530417 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ML654 UT WOS:A1993ML65400016 PM 8300756 ER PT J AU WEEKS, BS SCHNAPER, HW HANDY, M HOLLOWAY, E KLEINMAN, HK AF WEEKS, BS SCHNAPER, HW HANDY, M HOLLOWAY, E KLEINMAN, HK TI HUMAN T-LYMPHOCYTES SYNTHESIZE THE 92-KDA TYPE-IV COLLAGENASE (GELATINASE-B) SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID TISSUE INHIBITOR; INTERSTITIAL COLLAGENASE; HUMAN MACROPHAGES; INTERFERON-GAMMA; CELLS; ACTIVATION; EXPRESSION; ADHERENCE; LAMININ; INTEGRINS AB In order for T cells to exit the circulatory system, traverse the endothelial basement membrane, and arrive in target tissues, these cells must attach to and degrade basement membrane proteins. 12-O-tetradecanoylphorbol-13-acetate (TPA) has been shown to stimulate lymphoid cell adhesion to basement membrane components. We have used TPA to study the ability of human lymphoid cells to secrete type IV collagenases, enzymes capable of degrading basement membrane proteins. Here, we found that human primary T cells and H-9 lymphoid cells synthesize the 92 kDa type IV collagenase (gelatinase B) and TPA stimulates the synthesis and secretion of this protease. Peak TPA-stimulated gelatinase B secretion and mRNA accumulation were observed 9 hours after TPA treatment, while the peak adhesion to type IV collagen was observed only 3 hours after TPA treatment. The protein kinase C inhibitor, H-7, inhibited TPA-stimulated gelatinase B secretion. Both the primary T cells and H-9 lymphoid cells also expressed the mRNA for the tissue inhibitor of metalloproteinase-1 (TIMP-1). These data demonstrate that TPA -stimulated lymphoid cells adhere to type IV collagen and subsequently synthesize and secrete gelatinase B and TIMP-1. We conclude that lymphoid cell extravasation may involve cellular employment of adhesion mechanisms prior to degradation of the matrix, which is similar to the process of extravasation used by metastatic cells. (C) 1993 Wiley-Liss, Inc. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NIDR,IMMUNOL LAB,BETHESDA,MD 20892. NR 34 TC 61 Z9 64 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD DEC PY 1993 VL 157 IS 3 BP 644 EP 649 DI 10.1002/jcp.1041570326 PG 6 WC Cell Biology; Physiology SC Cell Biology; Physiology GA MK823 UT WOS:A1993MK82300025 PM 8253876 ER PT J AU RABIAN, B PETERSON, RA RICHTERS, J JENSEN, PS AF RABIAN, B PETERSON, RA RICHTERS, J JENSEN, PS TI ANXIETY SENSITIVITY AMONG ANXIOUS CHILDREN SO JOURNAL OF CLINICAL CHILD PSYCHOLOGY LA English DT Article ID DISORDERS; HYPERVENTILATION; POPULATION AB Employed the Diagnostic Interview Schedule for Children to show that children diagnosed with an anxiety disorder score significantly higher on the Childhood Anxiety Sensitivity Index (CASI) than nondiagnosed children. Interviews and self-report measures regarding the child were completed by 201 children and their parents from a metropolitan area military community who were participating in a National Institute of Mental Health epidemiological survey. An analysis of variance was used to compare CASI scoring across three groups: children receiving anxiety diagnoses, children receiving externalizing diagnoses but no anxiety diagnosis, and children receiving no diagnoses. Although scoring on the CASI differentiated anxious children from the no-diagnosis control group, it did not differentiate anxious children from those receiving externalizing diagnoses. Implications of the findings for the validity of the CASI, the issue of anxiety sensitivity as a component of some externalizing disorders, and suggestions for further investigation are discussed. C1 GEORGE WASHINGTON UNIV,WASHINGTON,DC 20052. NIMH,BETHESDA,MD 20892. RP RABIAN, B (reprint author), UNIV SO MISSISSIPPI,DEPT PSYCHOL,HATTIESBURG,MS 39406, USA. NR 23 TC 53 Z9 53 U1 1 U2 1 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 SN 0047-228X J9 J CLIN CHILD PSYCHOL JI J. Clin. Child Psychol. PD DEC PY 1993 VL 22 IS 4 BP 441 EP 446 DI 10.1207/s15374424jccp2204_4 PG 6 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA MK815 UT WOS:A1993MK81500004 ER PT J AU MASTORAKOS, G CHROUSOS, GP WEBER, JS AF MASTORAKOS, G CHROUSOS, GP WEBER, JS TI RECOMBINANT INTERLEUKIN-6 ACTIVATES THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS IN HUMANS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING FACTOR; HORMONE-SECRETION INVITRO; PLASMA-CORTISOL; RAT; RESPONSES; ADRENOCORTICOTROPIN; CYTOKINES; STRESS; IMMUNE AB The inflammatory cytokines, tumor necrosis factor-alpha, interleukin-1 alpha and -beta (IL-1 alpha and -beta), and IL-6 can activate the hypothalamic-pituitary-adrenal (HPA) axis. Tumor necrosis factor-alpha and IL-I have been tested in both experimental animals and humans, but their administration has been limited by significant toxicity, mainly severe hypotension. IL-6, on the other hand, has demonstrated modest toxicity in animals. We evaluated the ability of recombinant IL-6 to stimulate the human HPA axis in patients with cancer and a good performance status, who received daily morning sc injections of 30 mu g/kg IL-6 for 7 consecutive days, during the course of a phase I trial. IL-6 caused impressively marked and prolonged elevations of plasma ACTH and cortisol on the first day and blunted ACTH responses on the seventh day of treatment, perhaps as a result of increased baseline cortisol levels. The overall cortisol response, however, on the seventh day was of similar magnitude, suggesting that a new equilibrium in the feedback regulation of the HPA axis occurs with chronic IL-6 administration. The toxic effects of IL-6 were modest, suggesting that it might be useful for clinical testing of the HPA axis, as an alternative to the insulin tolerance test. C1 NCI, SURG BRANCH, BETHESDA, MD 20892 USA. RP MASTORAKOS, G (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N244, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 23 TC 402 Z9 413 U1 1 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1993 VL 77 IS 6 BP 1690 EP 1694 DI 10.1210/jc.77.6.1690 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MM202 UT WOS:A1993MM20200045 PM 8263159 ER PT J AU HIGGINS, M LENFANT, C AF HIGGINS, M LENFANT, C TI CONSIDER WHAT A LONG WAY YOUVE COME - THE WHITE QUEEN TO ALICE SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article ID CORONARY HEART-DISEASE; MORTALITY; CHOLESTEROL; ATHEROSCLEROSIS; ASSOCIATIONS; MORBIDITY; TRIALS RP HIGGINS, M (reprint author), NHLBI,EPIDEMIOL & BIOMETRY PROGRAM,2CO8 FED BLDG,7550 WISCONSIN AVE,BETHESDA,MD 20892, USA. NR 21 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD DEC PY 1993 VL 46 IS 12 BP 1347 EP 1350 DI 10.1016/0895-4356(93)90134-M PG 4 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA MP960 UT WOS:A1993MP96000002 PM 8263562 ER PT J AU SPORN, MB ROBERTS, AB AF SPORN, MB ROBERTS, AB TI A MAJOR ADVANCE IN THE USE OF GROWTH-FACTORS TO ENHANCE WOUND-HEALING SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID MATRIX GENE-EXPRESSION; FACTOR-BETA; PIG SKIN; ANGIOGENESIS; INVIVO; MODEL RP SPORN, MB (reprint author), NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892, USA. NR 16 TC 72 Z9 74 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1993 VL 92 IS 6 BP 2565 EP 2566 DI 10.1172/JCI116868 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ML643 UT WOS:A1993ML64300003 PM 8254012 ER PT J AU PILI, R CORDA, S PASSANITI, A ZIEGELSTEIN, RC HELDMAN, AW CAPOGROSSI, MC AF PILI, R CORDA, S PASSANITI, A ZIEGELSTEIN, RC HELDMAN, AW CAPOGROSSI, MC TI ENDOTHELIAL-CELL CA2+ INCREASES UPON TUMOR-CELL CONTACT AND MODULATES CELL-CELL ADHESION SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Note DE MELANOMA; ENDOTHELIUM; ADHESION; CALCIUM ID PLATELET-ACTIVATING-FACTOR; SURFACE; RECOGNITION; INTEGRINS; GMP-140; CALCIUM; SYSTEM; THAPSIGARGIN; METASTASIS; RETICULUM AB The signal transduction mechanisms involved in tumor cell adhesion to endothelial cells are still largely undefined. The effect of metastatic murine melanoma cell and human prostate carcinoma cell contact on cytosolic [Ca2+] of bovine artery endothelial cells was examined in indo-1-loaded endothelial cell monolayers. A rapid increase in endothelial cell [Ca2+] occurred on contact with tumor cells, but not on contact with 8-mum inert beads. A similar increase in endothelial cell [Ca2+] was observed with human neutrophils or monocyte-like lymphoma cells, but not with endothelial cells, red blood cells, and melanoma cell-conditioned medium. The increase in endothelial cell [Ca2+] was not inhibited by extracellular Ca2+ removal. In contrast, endothelial cell pretreatment with thapsigargin, which releases endoplasmic reticulum Ca2+ into the cytosol and depletes this Ca2+ store site, abolished the cytosolic [Ca2+] rise upon melanoma cell contact. Endothelial cell pretreatment with the membrane-permeant form of the Ca2+ chelator bis-(O-aminiophenoxyl)ethane-N,N,N',N'-tetraacetic acid blocked the increase in cytosolic [Ca2+]. Under static and dynamic flow conditions (0.46 dyn/cM2) bis-(O-aminophenoxyl)ethane-N,N,N',N'-tetraacetic acid pretreatment of bovine pulmonary artery endothelial cell monolayers inhibited melanoma cell adhesion to the endothelial cells. Thus, tumor cell contact with endothelial cells induces a rapid Ca2+ release from endothelial intercellular stores, which has a functional role in enhancing cell-cell adhesion. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224. NIA,BIOL CHEM LAB,CELL BIOL UNIT,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,DIV CARDIOL,BALTIMORE,MD 21224. RI Heldman, Alan/K-8784-2012 NR 29 TC 19 Z9 19 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1993 VL 92 IS 6 BP 3017 EP 3022 DI 10.1172/JCI116925 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ML643 UT WOS:A1993ML64300060 PM 8254056 ER PT J AU SCHWAN, TG SCHRUMPF, ME KARSTENS, RH CLOVER, JR WONG, J DAUGHERTY, M STRUTHERS, M ROSA, PA AF SCHWAN, TG SCHRUMPF, ME KARSTENS, RH CLOVER, JR WONG, J DAUGHERTY, M STRUTHERS, M ROSA, PA TI DISTRIBUTION AND MOLECULAR ANALYSIS OF LYME-DISEASE SPIROCHETES, BORRELIA-BURGDORFERI, ISOLATED FROM TICKS THROUGHOUT CALIFORNIA SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; MICE PEROMYSCUS-LEUCOPUS; MAJOR SURFACE-PROTEINS; BLACK-LEGGED TICK; IXODES-PACIFICUS; MONOCLONAL-ANTIBODY; GEL-ELECTROPHORESIS; INVITRO CULTIVATION; ANTIGEN P39; SP-NOV AB Previous studies describing the occurrence and molecular characteristics of Lyme disease spirochetes, Borrelia burgdorferi, from California have been restricted primarily to isolates obtained from the north coastal region of this large and ecologically diverse state. Our objective was to look for and examine B. burgdorferi organisms isolated from Ixodes pacificus ticks collected from numerous regions spanning most parts of California where this tick is found. Thirty-one isolates of B. burgdorferi were examined from individual or pooled I. pacificus ticks collected from 25 counties throughout the state. One isolate was obtained from ticks collected at Wawona Campground in Yosemite National Park, documenting the occurrence of the Lyme disease spirochete in an area of intensive human recreational use. One isolate from an Ixodes neotomae tick from an additional county was also examined. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoblot analysis, agarose gel electrophoresis, Southern blot analysis, and the polymerase chain reaction were used to examine the molecular and genetic determinants of these uncloned, low-passage-number isolates. All of the isolates were identified as B. burgdorferi by their protein profiles and reactivities with monoclonal and polyclonal antibodies, and all the isolates were typed by the polymerase chain reaction as North American-type spirochetes (B. burgdorferi sensu stricto). Although products of the ospAB locus were identified in protein analyses in all of the isolates, several isolates contained deleted forms of this locus that would result in the expression of chimeric OspA-OspB proteins. The analysis of OspC demonstrated that this protein was widely conserved among the isolates but was also quite variable in its molecular mass and the amount of it that was expressed. C1 NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840. CALIF DEPT HLTH SERV,DIV LABS,MICROBIAL DIS LAB,BERKELEY,CA 94704. RP SCHWAN, TG (reprint author), NIAID,ROCKY MT LABS,VECTORS & PATHOGENS LAB,ARTHROPOD BORNE DIS SECT,HAMILTON,MT 59840, USA. NR 74 TC 85 Z9 85 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 1993 VL 31 IS 12 BP 3096 EP 3108 PG 13 WC Microbiology SC Microbiology GA MG725 UT WOS:A1993MG72500003 PM 8308101 ER PT J AU CARTWRIGHT, CP STOCK, F KRUCZAKFILIPOV, PM GILL, VJ AF CARTWRIGHT, CP STOCK, F KRUCZAKFILIPOV, PM GILL, VJ TI RAPID METHOD FOR PRESUMPTIVE IDENTIFICATION OF CORYNEBACTERIUM-JEIKEIUM SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Note ID SKIN COLONIZATION; GROUP-JK AB Corynebacterium jeikeium causes systemic infections, particularly in immunocompromised hosts. A minitube assay has been developed for the presumptive identification of C. jeikeium. With our rapid sucrose-urea test and conventional biochemical tests, sixty isolates of gram-positive, catalase-positive bacilli were identified in our laboratory. Results indicated that our assay has a sensitivity of 100% and a specificity of 90%. RP CARTWRIGHT, CP (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,MICROBIOL SERV,BETHESDA,MD 20892, USA. NR 10 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 1993 VL 31 IS 12 BP 3320 EP 3322 PG 3 WC Microbiology SC Microbiology GA MG725 UT WOS:A1993MG72500040 PM 8308128 ER PT J AU TRIMBLE, EL ADAMS, JD VENA, D HAWKINS, MJ FRIEDMAN, MA FISHERMAN, JS CHRISTIAN, MC CANETTA, R ONETTO, N HAYN, R ARBUCK, SG AF TRIMBLE, EL ADAMS, JD VENA, D HAWKINS, MJ FRIEDMAN, MA FISHERMAN, JS CHRISTIAN, MC CANETTA, R ONETTO, N HAYN, R ARBUCK, SG TI PACLITAXEL FOR PLATINUM-REFRACTORY OVARIAN-CANCER - RESULTS FROM THE FIRST 1,000 PATIENTS REGISTERED TO NATIONAL-CANCER-INSTITUTE TREATMENT-REFERRAL-CENTER-9103 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TAXOL; AGENT C1 EMMES CORP,POTOMAC,MD. BRISTOL MYERS SQUIBB CO,WALLINGFORD,CT. NCI,BETHESDA,MD 20892. NR 12 TC 263 Z9 272 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC PY 1993 VL 11 IS 12 BP 2405 EP 2410 PG 6 WC Oncology SC Oncology GA MK118 UT WOS:A1993MK11800016 PM 7902426 ER PT J AU HORNE, MK MAYO, DJ WITTES, RE AF HORNE, MK MAYO, DJ WITTES, RE TI HEPARINIZED SALINE TO FLUSH GROSHONG CATHETERS SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter RP HORNE, MK (reprint author), NIH,BETHESDA,MD 20892, USA. NR 3 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC PY 1993 VL 11 IS 12 BP 2458 EP 2458 PG 1 WC Oncology SC Oncology GA MK118 UT WOS:A1993MK11800027 PM 8246036 ER PT J AU CORR, M BOYD, LF PADLAN, EA MARGULIES, DH AF CORR, M BOYD, LF PADLAN, EA MARGULIES, DH TI H-2D(D) EXPLOITS A 4 RESIDUE PEPTIDE BINDING MOTIF SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I MOLECULES; AMINO-ACID-SEQUENCE; TOXIC LYMPHOCYTES-T; VIRAL PEPTIDES; MHC MOLECULES; NUCLEOTIDE-SEQUENCES; STRUCTURAL FEATURES; CELL EPITOPES; ANTIGENS AB We have characterized the amino acid sequences of over 20 endogenous peptides bound by a soluble analog of H-2D(d), H-2D(s)d. Synthetic analogs corresponding to self, viral, tumor, or motif peptides were then tested for their ability to bind to H-2D(d) by serologic epitope induction assays using both purified soluble protein and cell surface H-2D(d). The dominant primary sequence motif included glycine at position 2, proline at position 3, and a hydrophobic COOH terminus: leucine, isoleucine, or phenylalanine at position 9 or 10. Ancillary support for high affinity binding was contributed by a positively charged residue at position 5. Three-dimensional computer models of H-2D(s)d/peptide complexes, based on the crystallographic structure of the human HLA-B27/peptide complex, showed that the basic residue at position 5 was in position to form a salt bridge with aspartic acid at position 156, a polymorphic residue of the H-2D(d) heavy (H) chain. Analysis of 28 such models, including 17 based on nonamer self-peptides, revealed considerable variation in the structure of the major histocompatibility complex (MHC) surrounding peptide residue 1, depending on the size and charge of the side chain. Interactions between the side chains of peptide residues 5 and 7, and 6 and 8 commonly occurred. Those peptide positions with limited sequence variability and least solvent accessibility may satisfy structural requirements for high affinity binding of the peptide to the MHC class I H chain, whereas the highly variable positions of the peptide (such as positions 4, 6, and 8) may contribute more to the T cell epitopes. C1 NIAID,IMMUNOL LAB,MOLEC BIOL SECT,BLDG 10,ROOM 11N311,BETHESDA,MD 20892. NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. RI Margulies, David/H-7089-2013 NR 83 TC 86 Z9 87 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 1 PY 1993 VL 178 IS 6 BP 1877 EP 1892 DI 10.1084/jem.178.6.1877 PG 16 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA MJ267 UT WOS:A1993MJ26700004 PM 8245770 ER PT J AU FREEMAN, GJ BORRIELLO, F HODES, RJ REISER, H GRIBBEN, JG NG, JW KIM, J GOLDBERG, JM HATHCOCK, K LASZLO, G LOMBARD, LA WANG, S GRAY, GS NADLER, LM SHARPE, AH AF FREEMAN, GJ BORRIELLO, F HODES, RJ REISER, H GRIBBEN, JG NG, JW KIM, J GOLDBERG, JM HATHCOCK, K LASZLO, G LOMBARD, LA WANG, S GRAY, GS NADLER, LM SHARPE, AH TI MURINE B7-2, AN ALTERNATIVE CTLA4 COUNTER-RECEPTOR THAT COSTIMULATES T-CELL PROLIFERATION AND INTERLEUKIN-2 PRODUCTION SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ACTIVATION ANTIGEN-B7; MOLECULAR-CLONING; B-CELLS; EXPRESSION; SIGNAL; SUPERFAMILY; INDUCTION; PROVIDES; CLONES; ANERGY AB The B7-1 molecule, expressed on antigen presenting cells (APC), provides a crucial costimulatory signal for T cell activation. Recent studies demonstrate the existence of alternative, non-B7-1 CTLA4 counter-receptors in mice and humans. Here, we describe the molecular cloning and demonstrate costimulatory function of the murine B7-2 (mB7-2) gene. Murine B7-2 cDNA encodes a member of the Ig supergene family that binds CTLA4-Ig and stains with the GL1 but not anti-mB7-1 mAb. Murine B7-2 costimulates the proliferation and interleukin 2 production of CD4+ T cells and this costimulation can be inhibited by either CTLA4-Ig or GL1 mAb. Identification of the B7-2 molecule will permit further manipulation of the B7:CD28/CTLA4 costimulatory pathway which has been shown to be involved in the prevention of tolerance, induction of tumor immunity, and most recently, in the pathogenesis of autoimmunity. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV LYMPHOCYTE BIOL,BOSTON,MA 02115. REPLIGEN CORP,CAMBRIDGE,MA 02139. BRIGHAM & WOMENS HOSP,DEPT PATHOL,DIV IMMUNOL RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NIA,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. RP FREEMAN, GJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV HEMATOL MALIGNANCIES,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA-40216]; NHLBI NIH HHS [5T33 HL07627]; NIAID NIH HHS [AI-33679] NR 32 TC 351 Z9 358 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 1 PY 1993 VL 178 IS 6 BP 2185 EP 2192 DI 10.1084/jem.178.6.2185 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA MJ267 UT WOS:A1993MJ26700033 PM 7504059 ER PT J AU GUY, HR DURELL, S AF GUY, HR DURELL, S TI USING SEQUENCE HOMOLOGY TO DEVELOP 3-DIMENSIONAL MODELS OF THE TRANSMEMBRANE PORTIONS OF POTASSIUM CHANNELS AND HOMOLOGOUS PROTEINS SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract C1 NCI,DCBDC,MATH BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD DEC PY 1993 VL 102 IS 6 BP A7 EP A8 PG 2 WC Physiology SC Physiology GA MN163 UT WOS:A1993MN16300027 ER PT J AU SOMOGYI, R MA, W SMALLWOOD, V BARKER, JL AF SOMOGYI, R MA, W SMALLWOOD, V BARKER, JL TI ONTOGENY OF 13 GABA(A) RECEPTOR SUBUNITS AND GAD IN RAT SPINAL-CORD SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract C1 NIH,NEUROPHYSIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD DEC PY 1993 VL 102 IS 6 BP A15 EP A15 PG 1 WC Physiology SC Physiology GA MN163 UT WOS:A1993MN16300046 ER PT J AU NAKAGOMI, O ISEGAWA, Y HOSHINO, Y ABOUDY, Y SHIF, I SILBERSTEIN, I NAKAGOMI, T UEDA, S SEARS, J FLORES, J AF NAKAGOMI, O ISEGAWA, Y HOSHINO, Y ABOUDY, Y SHIF, I SILBERSTEIN, I NAKAGOMI, T UEDA, S SEARS, J FLORES, J TI A NEW SEROTYPE OF THE OUTER CAPSID PROTEIN-VP4 SHARED BY AN UNUSUAL HUMAN ROTAVIRUS STRAIN-RO1845 AND CANINE ROTAVIRUSES SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID RNA-RNA HYBRIDIZATION; ACID-SEQUENCE ANALYSIS; FELINE ROTAVIRUS; VP4; IDENTIFICATION; NEUTRALIZATION; STRAIN; HEMAGGLUTINATION; SPECIFICITIES AB The VP4 protein of human rotavirus (HRV) strain Ro1845 and canine rotavirus strains K9 and CU-1 exhibited greater than 98% amino acid identity within their group, but showed less identity with VP4 proteins of other HRV and animal rotavirus strains, the simian rotavirus strain RRV VP4 being most similar to them (90% amino acid identity). To exclude the possibility that these three strains were members of the RRV VP4 serotype P3, neutralization studies were performed using antisera to reassortant viruses containing the VP4 gene from each of Ro1845, CU-1 and RRV. The result established close antigenic similarity among the VP4 proteins of Ro1845. K9 and CU-1 and revealed only a marginal degree of similarity between the VP4 proteins of these three strains and that of strain RRV. These sequence and serological data suggest that the VP4 proteins of Ro1845, K9 and CU-1 represent a new P serotype which we propose to assign P13. C1 OSAKA UNIV,DEPT PREVENT MED,MICROBIAL DIS RES INST,SUITA 560,JAPAN. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. CHAIM SHEBA MED CTR,CENT VIROL LAB,IL-52621 TEL HASHOMER,ISRAEL. RP NAKAGOMI, O (reprint author), AKITA UNIV,SCH MED,DEPT MICROBIOL,1-1-1 HONDO,AKITA 010,JAPAN. NR 26 TC 22 Z9 22 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD DEC PY 1993 VL 74 BP 2771 EP 2774 DI 10.1099/0022-1317-74-12-2771 PN 12 PG 4 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA MN275 UT WOS:A1993MN27500030 PM 8277285 ER PT J AU DIBRINO, M TSUCHIDA, T TURNER, RV PARKER, KC COLIGAN, JE BIDDISON, WE AF DIBRINO, M TSUCHIDA, T TURNER, RV PARKER, KC COLIGAN, JE BIDDISON, WE TI HLA-A1 AND HLA-A3 T-CELL EPITOPES DERIVED FROM INFLUENZA-VIRUS PROTEINS PREDICTED FROM PEPTIDE BINDING MOTIFS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CLASS-I MOLECULE; MATRIX PEPTIDE; MHC; SELF; ANTIGENS; SEQUENCE; HLA-B27; SPECIFICITY; RECOGNITION; RESOLUTION AB The potential value of peptide binding motifs of HLA class I molecules for the prediction of viral epitopes presented to T cells has been analyzed for two common HLA alleles. CTL generated against type A influenza virus recognize peptide epitopes derived from the nucleoprotein (NP) and basic polymerase 1 presented by HLA-A1, and epitopes derived from NP presented by HLA-A3. Distinct peptide binding motifs with characteristic anchor residues were previously identified for each of these class I molecules based on the sequences of endogenous peptides: for HLA-A1, position 3 = Asp or Glu and position 9 = Tyr; for HLA-A3, position 2 = Leu and position 9 = Lys or Tyr. Six peptides containing the HLA-A1 binding motif were identified within the sequences of the NP and basic polymerase 1 proteins, and one peptide containing the HLA-A3 motif was identified in the NP molecule. Three of the six HLA-A1 peptides and the one HLA-A3 NP peptide could bind to HLA-A1 or HLA-A3, respectively, in an in vitro peptide binding assay. Two of the HLA-A1-binding peptides could sensitize target cells for lysis by influenza virus-immune CTL populations restricted by HLA-A1 (NP 44-52 CTELKLSDY and PB1 591-599 VSDGGPNLY), and the one HLA-A3 NP peptide (NP 265-273 ILRGSVAHK) could sensitize target cells for lysis by HLA-A3-restricted influenza-immune CTL. Each peptide was also shown to be able to induce peptide-specific class I-restricted CTL in vitro, and the CTL generated against two of these peptides could specifically recognize virus-infected targets. Thus, these peptide binding motifs can be used to construct immunogenic synthetic epitopes which are capable of inducing antiviral T cell-mediated immune responses. C1 NINCDS,NEUROIMMUNOL BRANCH,MOLEC IMMUNOL SECT,BLDG 10,RM 5B 16,BETHESDA,MD 20892. NIAID,BIOL RESOURCES BRANCH,BETHESDA,MD 20892. OI Parker, Kenneth/0000-0002-6282-2478 NR 31 TC 125 Z9 126 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1993 VL 151 IS 11 BP 5930 EP 5935 PG 6 WC Immunology SC Immunology GA MH756 UT WOS:A1993MH75600005 PM 7504010 ER PT J AU YUI, K ISHIDA, Y KATSUMATA, M KOMORI, S CHUSED, TM ABE, R AF YUI, K ISHIDA, Y KATSUMATA, M KOMORI, S CHUSED, TM ABE, R TI 2 SEPARATE MECHANISMS OF T-CELL CLONAL ANERGY TO MLS-1(A) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; V-BETA-8.1 TRANSGENIC MICE; MONOCLONAL-ANTIBODY; ANTIGEN RECEPTOR; SELF-TOLERANCE; NEGATIVE SELECTION; MOLECULAR EVENTS; DELETION; REACTIVITY; DIFFERENTIATION AB T cell tolerance to superantigen can be mediated by clonal anergy in which Ag-specific mature T cells are physically present but are not able to mount an immune response. We induced T cell unresponsiveness to minor lymphocyte stimulations locus antigen (Mls)-1a in mice transgenic for TCR Vbeta8.1 in three different systems: 1) injection of Mls-1a spleen cells, 2) mating with Mls-1a mice, and 3) bone marrow (BM) chimeras in which Mls-1a is present only on nonhematopoietic cells. CD4+8-Vbeta8.1+ cells from all these groups did not proliferate in response to irradiated spleen cells from Mls-1a mice. We compared the response of these cells by T cell/stimulator cell conjugate formation, Ca2+ mobilization, and proliferation assays. The mechanisms underlying the unresponsiveness of these T cells appear to differ. CD4+8-Vbeta8.1+ cells from Mls-1a spleen cell-injected mice mobilized cytoplasmic Ca2+ but proliferated at a reduced level in response to cross-linking with anti-TCR mAb. However, these cells formed conjugates, mobilized Ca2+, and proliferated in response to MlS-1a when activated B cells were used as stimulators, although they produced reduced levels of IL-2. In Mls-1a/b Vbeta8.1 transgenic mice, a subset in CD4+8-Vbeta8.1+ cells did not mobilize cytoplasmic Ca2+ after TCR cross-linking. Their conjugate formation, Ca2+ mobilization, or proliferation in response to Mls-1a on activated B cells was undetectable. Finally, CD4+8-Vbeta8.1+ cells from the BM chimeras proliferated to TCR cross-linking at a partially reduced level and formed conjugates, mobilized Ca2+, and proliferated in response to Mls-1a on activated B cells. These features suggest that the mechanisms underlying the maintenance of anergy in Mls-1a spleen cell-injected mice are distinct from those in Mls-1a mice. C1 UNIV PENN,DEPT PATHOL & LAB MED,DIV IMMUNOL,PHILADELPHIA,PA 19104. NIAID,IMMUNOL LAB,ROCKVILLE,MD 20852. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20889. NR 44 TC 13 Z9 13 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1993 VL 151 IS 11 BP 6062 EP 6075 PG 14 WC Immunology SC Immunology GA MH756 UT WOS:A1993MH75600020 PM 8245451 ER PT J AU AHOUSE, JJ HAGERMAN, CL MITTAL, P GILBERT, DJ COPELAND, NG JENKINS, NA SIMISTER, NE AF AHOUSE, JJ HAGERMAN, CL MITTAL, P GILBERT, DJ COPELAND, NG JENKINS, NA SIMISTER, NE TI MOUSE MHC CLASS-I-LIKE FC-RECEPTOR ENCODED OUTSIDE THE MHC SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; MOLECULAR-CLONING; NEONATAL RAT; NUCLEOTIDE-SEQUENCE; POINT MUTATIONS; CDNA CLONE; EXPRESSION; GENES; TRANSPORT; ALLELES AB In many mammalian species antibodies transmitted from the mother provide humoral immunity to the young. Maternal IgG from milk is transported across the intestinal epithelium of neonatal rats by an Fc receptor (FcRn) that comprises an alpha-chain similar to the class I Ag of the MHC and beta2-microglobulin. Suckling mice also acquire antibodies by uptake from the gut. We made a neonatal mouse intestinal cDNA library and screened it with a probe encoding rat FcRn alpha-chain. The nucleotide and predicted amino acid sequences of the two positive clones were very similar to those of rat FcRn. Comparison of the FcRn domains to various MHC class I and CD1 molecules suggests a divergence of FcRn from MHC early in the mammalian lineage. We expressed one of these cDNA in mouse 3T3 fibroblasts. Cells that expressed the cDNA product bound the Fc fragment of IgG with the same pH dependence as neonatal rat intestinal epithelium. We detected RNA that hybridize with the mouse cDNA only in neonatal small intestine and fetal yolk sac, two tissues involved in IgG transport. These data show that the mouse cDNA code for FcRn alpha-chain. The mouse Fc-Rn alpha-chain is similar in sequence to the class I MHC Ag, encoded on chromosome 17 in the mouse. However, we find that the mouse FcRn gene lies outside the MHC, on chromosome 7. C1 BRANDEIS UNIV,ROSENSTIEL BASIC MED SCI RES CTR,WALTHAM,MA 02254. NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101]; NICHD NIH HHS [HD27691] NR 76 TC 124 Z9 128 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 DEC 1 PY 1993 VL 151 IS 11 BP 6076 EP 6088 PG 13 WC Immunology SC Immunology GA MH756 UT WOS:A1993MH75600021 PM 7504013 ER PT J AU SMYTH, MJ SAYERS, TJ WILTROUT, T POWERS, JC TRAPANI, JA AF SMYTH, MJ SAYERS, TJ WILTROUT, T POWERS, JC TRAPANI, JA TI MET-ASE - CLONING AND DISTINCT CHROMOSOMAL LOCATION OF A SERINE-PROTEASE PREFERENTIALLY EXPRESSED IN HUMAN NATURAL-KILLER-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOXIC LYMPHOCYTE-T; PORCINE PANCREATIC ELASTASE; GENE-EXPRESSION; HUMAN-LEUKOCYTE; MEDIATED LYSIS; GRANULES; ALPHA; CDNA; DNA; PURIFICATION AB A cDNA clone encoding a human NK serine protease was obtained by screening a lambda-gt10 library from the Lopez NK leukemia with the rat natural killer Met-ase (RNK-Met-1) cDNA clone. In Northern blot analysis human Met-ase (Hu-Met-1) cDNA hybridized with a 0.9-kb mRNA in two human NK leukemia cell lines, unstimulated human PBMC, and untreated purified CD3-CD56+ large granular lymphocytes. Unlike other members of the granzyme family that are highly expressed in activated peripheral T cells, the Hu-Met-I transcript was barely detected in a population of PMA and ionomycin or IL-2-treated high density T cells. Several in vitro cultured Burkitt lymphomas, chronic- and promyeloid leukemias, acute lymphoblastic leukemias, and colon and ovarian carcinomas did not express Hu-Met-1 mRNA. Hu-Met-1 mRNA expression in a small number of human T cell tumor lines did not correlate with any particular phenotype or stage of development. The presence of Hu-Met-1 mRNA closely correlated with the Met-ase activity of cellular lysates prepared from these various human peripheral blood subsets and in vitro cultured cell lines. Met-ase activity detected in whole cell lysates of cytotoxic lymphocytes was associated with the cytoplasmic granules of these cells. The nucleotide sequence of the Hu-Met-I cDNA clone encodes a predicted serine protease of 257 amino acids. The predicted protein is an active enzyme of 232 amino acids with a calculated unglycosylated m.w. of 27,100. Hu-Met-1 is 66% identical to RNK-Met-1 at the amino acid level. The human and rat mature protein sequences conserve the active site His, Asp, and Ser amino acids that form the catalytic triad of serine proteases, all 8 cysteine residues, and several amino acids critical in the formation of the substrate binding pocket. The gene for the Hu-Met-1 serine protease is located on chromosome 19, which distinguishes it from any other member of the human granzyme family. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYN CORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. GEORGIA INST TECHNOL,SCH CHEM & BIOCHEM,ATLANTA,GA 30332. RP SMYTH, MJ (reprint author), AUSTIN HOSP,AUSTIN RES INST,CELLULAR CYTOTOX LAB,STUDLEY RD,HEIDELBERG,VIC 3084,AUSTRALIA. RI Sayers, Thomas/G-4859-2015; Smyth, Mark/H-8709-2014 OI Smyth, Mark/0000-0001-7098-7240 FU NCI NIH HHS [CM42212, N01-CO-74102]; NHLBI NIH HHS [HL29307]; Wellcome Trust NR 46 TC 61 Z9 63 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1993 VL 151 IS 11 BP 6195 EP 6205 PG 11 WC Immunology SC Immunology GA MH756 UT WOS:A1993MH75600032 PM 8245461 ER PT J AU YOSHIMURA, T JOHNSON, DG AF YOSHIMURA, T JOHNSON, DG TI CDNA CLONING AND EXPRESSION OF GUINEA-PIG NEUTROPHIL ATTRACTANT PROTEIN-1 (NAP-1) - NAP-1 IS HIGHLY CONSERVED IN GUINEA-PIG SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; MACROPHAGE INFLAMMATORY PROTEIN-2; BLOOD MONONUCLEAR LEUKOCYTES; AMINO-ACID-SEQUENCE; HUMAN INTERLEUKIN-8 RECEPTOR; GROWTH-STIMULATORY ACTIVITY; PERITONEAL-CAVITY INVIVO; CHEMOTACTIC FACTOR MDNCF; ACTIVATION PROTEIN-1; MOLECULAR-CLONING AB cDNA for neutrophil attractant protein-1 (NAP-1, also known as IL-8) was cloned from Con A-stimulated guinea pig spleen cells with human NAP-1 cDNA as a probe. Guinea pig NAP-1 cDNA is composed of 1433 bp with an open reading frame which encodes for a 101-amino-acid protein. Guinea pig NAP-1 had 70% amino acid sequence similarity to human NAP-1, which was much higher than a similarity between human and guinea pig monocyte chemoattractant protein-1 (MCP-1) (56%). Nucleotide sequence similarity within the coding region was 75%. To confirm its biological activity in guinea pig, recombinant guinea pig NAP-1 was expressed in COS-7 cells then purified. N-terminal sequence analysis gave two different N-termini at position 23 (Met) or 24 (Val). The two proteins showed their peak activity for guinea pig neutrophils at the concentration of 1 mug/ml (10(-7) M). Despite its high similarity to human NAP-1, the responsiveness of human neutrophils to guinea pig NAP-1 was minimum. Recombinant guinea pig NAP-1 caused strong neutrophil infiltration after intradermal injection into guinea pig skin. Since guinea pig is classified as a rodent, it was of interest to know whether human NAP-1 cDNA hybridizes to genomic DNA of other rodents such as mouse or rat, in which a NAP-1 homologue has not been found. Under low stringency conditions, human NAP-1 cDNA hybridized to human, rabbit, and guinea pig DNA, but not to mouse or rat DNA. Unlike NAP-1, human MCP-1 cDNA hybridized to genomic DNA of rabbit, guinea pig, mouse, and rat; MCP-1 cDNA have been cloned from these species. The apparent absence of a NAP-1 gene in mouse or rat makes this chemoattractant unique among the members of the protein family to which NAP-1 and MCP-1 belong. C1 PROGRAM RESOURCES INC DYN CORP,AIDS VACCINE PROGRAM,PROT CHEM SECT,FREDERICK,MD 21702. RP YOSHIMURA, T (reprint author), NCI,FCRDC,IMMUNOPATHOL SECT,IMMUNOBIOL LAB,BLDG 560,ROOM 12-71,FREDERICK,MD 21702, USA. NR 51 TC 54 Z9 56 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1993 VL 151 IS 11 BP 6225 EP 6236 PG 12 WC Immunology SC Immunology GA MH756 UT WOS:A1993MH75600035 PM 7504015 ER PT J AU DHIBJALBUT, SS COWAN, EP AF DHIBJALBUT, SS COWAN, EP TI DIRECT EVIDENCE THAT INTERFERON-BETA MEDIATES ENHANCED HLA-CLASS-I EXPRESSION IN MEASLES VIRUS-INFECTED CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR NECROSIS FACTOR; GLIAL-CELLS; BRAIN-CELLS; T-CELLS; ANTIGENS; ASTROCYTES; INDUCTION; RNA AB Viral infection results in enhancement of HLA-class I expression in a number of cell types, including glial cells, which normally do not express these molecules. This enhancement may occur through a direct interaction between a viral component and the HLA-class I gene or indirectly through virus-induced soluble factors produced by infected cells. These include cytokines such as IFN-gamma, IFN-alpha/beta, and TNF-alpha, known to enhance class I expression. Measles virus (MV) infection of a human glioma cell line (U-105 MG) and of primary human umbilical vein endothelial cells enhances the expression of HLA-class I molecules on these cells. The enhancement of HLA-class I is dependent on infectious virus, as antibody-neutralized MV has no effect on class I expression. In this study, we demonstrate the presence of an HLA-class I-enhancing factor in supernatants from MV-infected cells. The supernatant class I-enhancing factor is not IFN-gamma, IFN-alpha, or TNF-alpha because MV-infected cells did not produce measurable levels of these cytokines as detected by immunoassay or polymerase chain reaction. In contrast, IFN-beta is produced by the infected cells and the supernatant class I-enhancing factor could be entirely neutralized by antibodies to IFN-beta, but not antibodies to IFN-alpha, TNF-alpha, or non-immune sera. Furthermore, preincubation of cells with neutralizing antibodies to IFN-beta prior to infection blocked MV enhancement of HLA-class I completely in the U-105 MG cells and by as much as 74% in the umbilical vein endothelial cells. The results of these experiments provide direct evidence that enhanced HLA-class I expression in MV-infected cells is mediated primarily by IFN-beta. C1 UNIV MARYLAND,DEPT NEUROSURG,BALTIMORE,MD 21201. NIH,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. VET ADM MED CTR,BALTIMORE,MD 21218. FU NINDS NIH HHS [2 P50 NS 20022-09A1] NR 27 TC 42 Z9 42 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1993 VL 151 IS 11 BP 6248 EP 6258 PG 11 WC Immunology SC Immunology GA MH756 UT WOS:A1993MH75600037 PM 8245464 ER PT J AU RIXON, MW GOURLIE, BB KAPLAN, DA SCHLOM, J MEZES, PS AF RIXON, MW GOURLIE, BB KAPLAN, DA SCHLOM, J MEZES, PS TI PREFERENTIAL USE OF A H-CHAIN V-REGION IN ANTITUMOR-ASSOCIATED GLYCOPROTEIN-72 MONOCLONAL-ANTIBODIES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CANCER-PATIENTS; GENE SEGMENTS; COLON CANCER; MAB B72.3; CARCINOMA; MICE; AUTOANTIBODIES; SEQUENCES; ANTIGEN; FAMILY AB The DNA sequence of the mouse H chain V regions from five hybridomas directed against the human tumor Ag tumor-associated glycoprotein-72 (TAG-72) have been determined. This includes a previously determined V(H) gene sequence from a first-generation anti-TAG-72 mAb, B72.3, and the V(H) gene sequences from four second-generation anti-TAG-72 mAb, CC49, CC83, CC46, and CC92. A sequence comparison revealed a high degree of shared sequence identity between the five productively rearranged V(H) genes, suggesting derivation from a common germ line V region gene. In the process of cloning the unrearranged germ line gene, two highly related V(H) germ line genes were identified and designated V(H)alphaTAG-1 and V(H)alphaTAG-2. A comparison of the productively rearranged anti-TAG-72 V(H) sequences with the two germ line V(H) genes demonstrated that they were all derived from V(H)alphaTAG-1. In contrast, the L chain V regions are all derived from separate germ line V region genes. The preferential use of V(H)alphaTAG-1 in these five mouse hybridomas suggests that V(H)alphaTAG-1 is a preferred anti-TAG-72 H V chain region germ line gene and that the H chain plays a predominant role in the recognition of this Ag. C1 NIH,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. RP RIXON, MW (reprint author), DOW CHEM CO USA,CENT RES BIOPROD LAB,1701 BLDG,MIDLAND,MI 48674, USA. NR 42 TC 14 Z9 14 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1993 VL 151 IS 11 BP 6559 EP 6568 PG 10 WC Immunology SC Immunology GA MH756 UT WOS:A1993MH75600069 PM 8245485 ER PT J AU BUKH, J WANTZIN, P KROGSGAARD, K KNUDSEN, F PURCELL, RH MILLER, RH AF BUKH, J WANTZIN, P KROGSGAARD, K KNUDSEN, F PURCELL, RH MILLER, RH TI HIGH PREVALENCE OF HEPATITIS-C VIRUS (HCV) RNA IN DIALYSIS PATIENTS - FAILURE OF COMMERCIALLY AVAILABLE ANTIBODY TESTS TO IDENTIFY A SIGNIFICANT NUMBER OF PATIENTS WITH HCV INFECTION SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID NON-B-HEPATITIS; POLYMERASE CHAIN-REACTION; CHRONIC-HEMODIALYSIS PATIENTS; NON-A-HEPATITIS; RECOMBINANT IMMUNOBLOT; TRANSPLANT RECIPIENTS; VIRAL-HEPATITIS; ASSAY; SEQUENCES; MARKERS AB Results of serologic tests were correlated with hepatitis C virus (HCV) viremia, determined by a cDNA polymerase chain reaction assay to detect HCV RNA, in 340 Danish dialysis patients; of these, 28 (8.2%) were positive for antibodies to HCV (anti-HCV) with second-generation ELISAs. HCV RNA was found in sera from 27 of these 28 anti-HCV-positive patients. However, 8 dialysis patients had detectable levels of HCV RNA but were anti-HCV-negative with second-generation ELISAs. Among the 35 HCV-infected dialysis patients 16 were positive, 7 indeterminate, and 12 negative with the second-generation RIBA. More than 60% of patients with evidence of ongoing liver disease had HCV infection. Thus, current commercially available antibody tests did not accurately reflect the HCV status in dialysis patients. A relatively high prevalence (> 10%) of HCV RNA, closely associated with liver disease, was found among dialysis patients in a low-prevalence area of the world. C1 HVIDOVRE UNIV HOSP,DEPT CLIN IMMUNOL,DK-2650 HVIDOVRE,DENMARK. HVIDOVRE UNIV HOSP,DEPT NEPHROL,DK-2650 HVIDOVRE,DENMARK. RIGSHOSP,DEPT NEPHROL,DK-2100 COPENHAGEN,DENMARK. RIGSHOSP,DEPT INFECT DIS,DK-2100 COPENHAGEN,DENMARK. HERLEV HOSP,DEPT NEPHROL,DK-2730 HERLEV,DENMARK. RP BUKH, J (reprint author), NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BLDG 7,ROOM 201,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 41 TC 153 Z9 153 U1 1 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1993 VL 168 IS 6 BP 1343 EP 1348 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA MJ709 UT WOS:A1993MJ70900001 PM 7504031 ER PT J AU BROUWERS, P HEYES, MP MOSS, HA WOLTERS, PL POPLACK, DG MARKEY, SP PIZZO, PA AF BROUWERS, P HEYES, MP MOSS, HA WOLTERS, PL POPLACK, DG MARKEY, SP PIZZO, PA TI QUINOLINIC ACID IN THE CEREBROSPINAL-FLUID OF CHILDREN WITH SYMPTOMATIC HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 DISEASE - RELATIONSHIPS TO CLINICAL STATUS AND THERAPEUTIC RESPONSE SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; TUMOR-NECROSIS-FACTOR; HIV-1 INFECTION; PROGRESSIVE ENCEPHALOPATHY; NEUROACTIVE KYNURENINES; CONTINUOUS-INFUSION; INTERFERON-GAMMA; L-TRYPTOPHAN; FACTOR-ALPHA; RAT-BRAIN AB Quinolinic acid (QUIN) is a neurotoxin implicated in the neurologic deficits associated with human immunodeficiency virus type 1 (HIV-1) infection. Forty children with symptomatic HIV-1 disease had elevated (P < .001) cerebrospinal fluid (CSF) QUIN levels (55.8 +/- 8.9 nM) compared with controls (14.9 +/- 3.0 nM). Age-adjusted CSF QUIN concentrations in HIV-1-infected children were predicted by the general index of mental abilities (GIMA, from an age-appropriate intelligence test; r = -0.45, P < .01). Zidovudine therapy reduced CSF QUIN from 64.1 +/- 16.3 to 19.7 +/- 5.2 nM (P < .01; N = 16) and increased GIMA from 76.8 +/- 5.2 to 87.2 +/- 6.3 (P < .001). Encephalopathic HIV-1-infected patients had higher CSF QUIN levels than patients without encephalopathy (79.6 +/- 16.1 vs. 32.7 +/- 6.7 nM, P < .01). CSF QUIN concentrations were also higher (P < .001) in patients who died less-than-or-equal-to 3 years after their baseline assessment, compared with those who were still alive. These results warrant further investigation of CSF QUIN in HIV-infected children as a mediator of neurologic dysfunction and a supplemental marker of neurologic disease, particularly when combined with measures of neurocognitive functioning. C1 NCI,CTR MED ILLNESS COUNSELING,PEDIAT BRANCH,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,BETHESDA,MD 20892. NR 66 TC 61 Z9 63 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1993 VL 168 IS 6 BP 1380 EP 1386 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA MJ709 UT WOS:A1993MJ70900007 PM 8245522 ER PT J AU BELSHE, RB CLEMENTS, ML DOLIN, R GRAHAM, BS MCELRATH, J GORSE, GJ SCHWARTZ, D KEEFER, MC WRIGHT, P COREY, L BOLOGNESI, DP MATTHEWS, TJ STABLEIN, DM OBRIEN, FS EIBL, M DORNER, F KOFF, W AF BELSHE, RB CLEMENTS, ML DOLIN, R GRAHAM, BS MCELRATH, J GORSE, GJ SCHWARTZ, D KEEFER, MC WRIGHT, P COREY, L BOLOGNESI, DP MATTHEWS, TJ STABLEIN, DM OBRIEN, FS EIBL, M DORNER, F KOFF, W TI SAFETY AND IMMUNOGENICITY OF A FULLY GLYCOSYLATED RECOMBINANT GP160 HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 VACCINE IN SUBJECTS AT LOW-RISK OF INFECTION SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID DEPENDENT CELLULAR CYTOTOXICITY; HIV-1; GLYCOPROTEIN; ANTIBODIES; IMMUNIZATION; CHIMPANZEES; MACAQUES; INDIVIDUALS; PROTECTION; CATS AB Recombinant gp160 derived from human immunodeficiency virus type 1 (HIV-1)IIIB and produced in mammalian tissue culture cells using a vaccinia virus expression system (rgp160-mam) was evaluated as a vaccine in combination with alum and deoxycholate adjuvant. Sixty low-risk, uninfected subjects received 12.5 mug, 50.0 mug, or adjuvant control at 0, 1, 6, and 12 months in a randomized, double-blind dose-escalation study. A single injection of 200 mug of vaccine was given at 18 months in an open study to 9 vaccinees who had received 50 mug. The vaccine was safe. Six of 16 subjects receiving 50,ug developed neutralizing antibody to HIV-1IIIB. Seven of the 9 boosted with 200,ug of vaccine at 18 months developed neutralizing antibodies. Lymphocyte proliferation to rgp160-mam and baculovirus-derived rgp160- and rgp120 was induced in both groups (12.5 and 50.0 mug) and appeared after the first dose. Further studies with higher doses of rgp160-mam and vaccines derived from other strains of HIV-1 are warranted. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. EMMES CORP,POTOMAC,MD. NIAID,BETHESDA,MD 20892. UNIV ROCHESTER,SCH MED & DENT,ROCHESTER,NY 14642. VANDERBILT UNIV,MED CTR,SCH MED,NASHVILLE,TN 37232. UNIV WASHINGTON,SCH MED,SEATTLE,WA 98195. DUKE UNIV,SCH MED,DURHAM,NC 27706. IMMUNO AG WIEN,VIENNA,AUSTRIA. RP BELSHE, RB (reprint author), ST LOUIS UNIV,SCH MED,DEPT MED,DIV INFECT DIS,1402 S GRAND BLVD,ST LOUIS,MO 63104, USA. FU NIAID NIH HHS [AI-05064, AI-05061, AI-05063] NR 29 TC 77 Z9 78 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1993 VL 168 IS 6 BP 1387 EP 1395 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA MJ709 UT WOS:A1993MJ70900008 PM 8245523 ER PT J AU DESANTIS, C ROBBIONI, P LONGHI, R LOPALCO, L SICCARDI, AG BERETTA, A ROBERTS, NJ AF DESANTIS, C ROBBIONI, P LONGHI, R LOPALCO, L SICCARDI, AG BERETTA, A ROBERTS, NJ TI CROSS-REACTIVE RESPONSE TO HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) GP120 AND HLA CLASS-I HEAVY-CHAINS INDUCED BY RECEIPT OF HIV-1-DERIVED ENVELOPE VACCINES SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID T-CELL; PROTECTION; MACAQUES; GP160; IMMUNOGENICITY; EPITOPE; PEPTIDE; PATHOGENESIS; ANTIGENICITY; CHIMPANZEES AB Autoantibodies specific to HLA class I antigens were detected in the sera of persons vaccinated with human immunodeficiency virus type 1-derived recombinant vaccines by using synthetic peptides representing the amino acid sequences recognized by an HLA class I/gp120 cross-reactive monoclonal antibody. Study subjects received recombinant vaccinia gp160 (vacc-env) alone, vacc-env followed by one dose of recombinant gp160 (rgp160, 640 mug), or four doses of rgp 160 alone (640 or 80 mug). All sera from vacc-env/rgp160-vaccinated subjects contained HLA/gp 1 20 cross-reactive antibodies, as did all sera from recipients of the rgp160 alone at 640 mug/dose. In contrast, none of the sera from subjects who received either the vacc-env alone or the 80 mug/dose rgp160 alone contained detectable HLA cross-reactive antibodies, and these same sera showed little or no envelope reactivity on Western blot. The results showed a striking correlation between immunogenicity and the induction of cross-reactive antibodies by the rgp160 vaccine. C1 OSPED SAN RAFFAELE,DEPT BIOL & TECHNOL RES,VIA OLGETTINA 50,I-20132 MILAN,ITALY. UNIV ROCHESTER,SCH MED & DENT,DEPT MED,ROCHESTER,NY 14642. NIAID,AIDS VACCINE CLIN TRIALS NETWORK,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-27658] NR 31 TC 25 Z9 25 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1993 VL 168 IS 6 BP 1396 EP 1403 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA MJ709 UT WOS:A1993MJ70900009 PM 8245524 ER PT J AU NIU, MT STEIN, DS SCHNITTMAN, SM AF NIU, MT STEIN, DS SCHNITTMAN, SM TI PRIMARY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION - REVIEW OF PATHOGENESIS AND EARLY TREATMENT INTERVENTION IN HUMANS AND ANIMAL RETROVIRUS INFECTIONS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PRIMARY HIV-INFECTION; SCID-HU MICE; POSTEXPOSURE CHEMOPROPHYLAXIS; PROPHYLACTIC ZIDOVUDINE; OCCUPATIONAL EXPOSURE; INTERFERON-ALPHA; CLINICAL COURSE; RHESUS-MONKEYS; 3'-AZIDO-3'-DEOXYTHYMIDINE; DISEASE AB Primary human immunodeficiency virus type 1 (HIV-1) infection can present clinically as the abrupt onset of a febrile illness resembling acute mononucleosis. The symptoms coincide with high titers of culturable plasma viremia, cell-associated virus, and antigenemia, which rapidly decrease coincident with the emergence of detectable HIV-specific antibody and HIV-specific cytotoxic T lymphocytes. This article reviews the human and animal model data on the virologic and immunologic events that occur during primary HIV-1 and animal retrovirus infections, evaluates the prophylactic treatment experience of retrovirus infections in the animal model, and provides a plausible rationale for treatment intervention of primary HIV-1 infection in humans. Recent work delineating the pathogenesis of primary HIV-1 infection provides insight into the major mechanisms of viral dissemination and host immune response. The results from retrovirus-infected animal models treated with antiviral agents suggests that therapy at the time of viral dissemination may be an effective strategy that may modify disease progression. Clinical trials to evaluate this approach are in progress. RP NIU, MT (reprint author), NIAID,MED BRANCH,DIV AIDS,CLIN RES PROGRAM,6003 EXECTUT BLVD,BETHESDA,MD 20892, USA. NR 81 TC 118 Z9 120 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1993 VL 168 IS 6 BP 1490 EP 1501 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA MJ709 UT WOS:A1993MJ70900023 PM 8245534 ER PT J AU ROILIDES, E HOLMES, A BLAKE, C PIZZO, PA WALSH, TJ AF ROILIDES, E HOLMES, A BLAKE, C PIZZO, PA WALSH, TJ TI DEFECTIVE ANTIFUNGAL ACTIVITY OF MONOCYTE-DERIVED MACROPHAGES FROM HUMAN IMMUNODEFICIENCY VIRUS-INFECTED CHILDREN AGAINST ASPERGILLUS-FUMIGATUS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID MONONUCLEAR; INVITRO; SYSTEM AB Invasive aspergillosis recently has been encountered in adults and children with human immunodeficiency virus (HIV) infection even without known risk factors, such as neutropenia or corticosteroid therapy. Macrophages play a significant role in the host defenses against Aspergillus organisms by ingesting conidia and preventing their germination to hyphae. The antifungal activity of peripheral blood monocyte-derived macrophages (MDM) from 19 HIV-infected children was compared with that of 16 normal controls. The phagocytic activity of patients' MDM, measured as percentage of phagocytosis, was significantly decreased compared with normal donors (P = .014). In addition, the inhibitory activity of MDM on germination of intracellular A. fumigatus conidia was significantly impaired in patients compared with normal controls (P = .016). There was no significant difference in the defects between patients with lower or higher CD4 lymphocyte counts. Impairment of antifungal activity of macrophages may contribute to the susceptibility of HIV-infected patients to aspergillosis. C1 NCI,INFECT DIS SECT,PEDIAT BRANCH,BLDG 10,ROOM 13N240,BETHESDA,MD 20892. NR 15 TC 48 Z9 50 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1993 VL 168 IS 6 BP 1562 EP 1565 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA MJ709 UT WOS:A1993MJ70900038 PM 8245547 ER PT J AU NIU, MT STEIN, DS SCHNITTMAN, SM AF NIU, MT STEIN, DS SCHNITTMAN, SM TI TREATMENT TRIALS FOR PRIMARY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID ZIDOVUDINE RP NIU, MT (reprint author), NIAID,MED BRANCH,CLIN RES PROGRAM,6003 EXECUTIVE BLVD,BETHESDA,MD 20892, USA. NR 10 TC 4 Z9 4 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1993 VL 168 IS 6 BP 1601 EP 1602 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA MJ709 UT WOS:A1993MJ70900053 PM 8245559 ER PT J AU LEE, MG BORKOWSKI, TA UDEY, MC AF LEE, MG BORKOWSKI, TA UDEY, MC TI REGULATION OF EXPRESSION OF B7 BY MURINE LANGERHANS CELLS - A DIRECT RELATIONSHIP BETWEEN B7 MESSENGER-RNA LEVELS AND THE LEVEL OF SURFACE EXPRESSION OF B7 BY LANGERHANS CELLS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Note DE CD28; CTLA-4; COSTIMULATORY MOLECULES; ACCESSORY CELLS ID COLONY-STIMULATING FACTOR; ANTIGEN-PRESENTING CELLS; DENDRITIC CELLS; ACTIVATION ANTIGEN-B7; IA-ANTIGEN; T-CELLS; INDUCTION; INVITRO; B7/BB1; GENERATION AB Cultured BALB/c epidermal Langerhans cells express high levels of the costimulatory molecule B7 on their surfaces relative to levels expressed on fresh Langerhans cells. Quantitation of relative amounts of B7 mRNA in fresh epidermal cells and cultured epidermal cells following amplification of mRNA signals via reverse transcriptase-polymerase chain reaction, hybridization of PCR products with radiolabeled internal oligonucleotide probes, resolution of hybrids in non-denaturing polyacrylamide gels, and detection by autoradiography revealed dramatically (approximately one thousandfold) higher levels of B7 mRNA in cultured epidermal cells (10-40% I-A(+)) as compared with fresh epidermal cells(1-4% I-A(+)). Levels of B7 mRNA in cultured epidermal cells were also substantially greater than those detected in a reference B lymphoma cell line (CH-1). Analysis of B7 mRNA expression in subpopulations of cultured epidermal cells demonstrated that essentially all of the B7 mRNA was present in Langerhans cells; cells bearing I-A and CD45 antigens. Cultured keratinocytes did not contain appreciable amounts of B7 mRNA. These results are consistent with previous data regarding surface expression of B7 by cLC and also demonstrate that fLC are essentially devoid of B7 mRNA and surface protein. C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NR 34 TC 41 Z9 41 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 1993 VL 101 IS 6 BP 883 EP 886 DI 10.1111/1523-1747.ep12371712 PG 4 WC Dermatology SC Dermatology GA ML282 UT WOS:A1993ML28200022 PM 7504029 ER PT J AU LEVER, JR CARROLL, FI PATEL, A ABRAHAM, P BOJA, J LEWIN, A LEW, R AF LEVER, JR CARROLL, FI PATEL, A ABRAHAM, P BOJA, J LEWIN, A LEW, R TI RADIOSYNTHESIS OF A PHOTOAFFINITY PROBE FOR THE COCAINE RECEPTOR OF THE DOPAMINE TRANSPORTER - 3-BETA-(P-CHLOROPHENYL)TROPAN-2-BETA-CARBOXYLIC ACID M-([I-125]-IODO)-P-AZIDOPHENETHYL ESTER ([I-125]-RTI-82) SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE RADIOIODINATION; I-125; DOPAMINE TRANSPORTER; PHOTOAFFINITY LABELING; COCAINE ID CARRIER; PROTEIN AB The tropane alkaloid RTI-82, an iodoarylazide, has been labeled with iodine-125 for use as a photoaffinity probe for the cocaine binding site of the dopamine transporter. The one-flask radiosynthesis involves no-carrier-added electrophilic radioiodination of the corresponding aniline followed by diazotization and treatment with sodium azide. Isolation by reverse phase HPLC and solid phase extraction gives [I-125]-RTI-82 in good yield (76 +/- 7%, n = 6), high radiochemical purity (> 99.8%), and high specific radioactivity (1490 - 1880 mCi/mumol). C1 RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NIDA,ADDICT RES CTR,NEUROSCI BRANCH,BALTIMORE,MD 21224. RP LEVER, JR (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD 21205, USA. NR 19 TC 15 Z9 15 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD DEC PY 1993 VL 33 IS 12 BP 1131 EP 1137 DI 10.1002/jlcr.2580331207 PG 7 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA MJ209 UT WOS:A1993MJ20900006 ER PT J AU KELVIN, DJ MICHIEL, DF JOHNSTON, JA LLOYD, AR SPRENGER, H OPPENHEIM, JJ WANG, JM AF KELVIN, DJ MICHIEL, DF JOHNSTON, JA LLOYD, AR SPRENGER, H OPPENHEIM, JJ WANG, JM TI CHEMOKINES AND SERPENTINES - THE MOLECULAR-BIOLOGY OF CHEMOKINE RECEPTORS SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE CHEMOTAXIS; MIGRATION; G-PROTEINS; INFLAMMATION; CYTOKINES ID HUMAN INTERLEUKIN-8 RECEPTOR; NEUTROPHIL-ACTIVATING PEPTIDE-2; CELL-SURFACE RECEPTORS; HIGH-AFFINITY; HUMAN MONOCYTES; IDENTIFICATION; EXPRESSION; BINDING; PROTEIN-1; CYTOKINE AB Chemokines are pro-inflammatory molecules with a diverse array of biological and biochemical functions. These molecules induce the migration of a number of leukocyte subsets including monocytes, neutrophils, and T-cells. The recent cloning of the IL-8, GRO, and MIP-1alpha chemokine receptors revealed that these glycoproteins belong to the serpentine family of seven transmembrane G-protein-coupled receptors. Other members of this family include the chemotactic receptors for fMLP and C5a, indicating that a common pathway for eliciting the directional migration of leukocytes is probably transduced via G proteins. Ligand binding to chemokine receptors is complex, featured by multiple chemokines binding to a single receptor and multiple receptors binding a specific ligand. Future directions in this field appear to be focused on the cloning of novel receptors and the identification of ligands for orphaned receptors. C1 PRINCE HENRY HOSP,DEPT INFECT DIS,LITTLE BAY,NSW 2036,AUSTRALIA. PHILLIPS UNIV MARBURG,INST IMMUNOL,MARBURG,GERMANY. RP KELVIN, DJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 38 TC 161 Z9 162 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD DEC PY 1993 VL 54 IS 6 BP 604 EP 612 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA MK131 UT WOS:A1993MK13100015 PM 8245714 ER PT J AU IKEWAKI, K RADER, DJ SCHAEFER, JR FAIRWELL, T ZECH, LA BREWER, HB AF IKEWAKI, K RADER, DJ SCHAEFER, JR FAIRWELL, T ZECH, LA BREWER, HB TI EVALUATION OF APOA-I KINETICS IN HUMANS USING SIMULTANEOUS ENDOGENOUS STABLE-ISOTOPE AND EXOGENOUS RADIOTRACER METHODS SO JOURNAL OF LIPID RESEARCH LA English DT Article DE RADIOTRACER; STABLE ISOTOPES; HIGH DENSITY LIPOPROTEINS ID HIGH-DENSITY-LIPOPROTEIN; APOLIPOPROTEIN-A-I; TRIGLYCERIDE-RICH LIPOPROTEINS; ISCHEMIC HEART-DISEASE; INVIVO METABOLISM; DEUTERATED LEUCINE; B-100 KINETICS; PLASMA; HYPERTRIGLYCERIDEMIA; HYPOALPHALIPOPROTEINEMIA AB Apolipoprotein A-I is the major apolipoprotein constituent of high density lipoproteins (HDL). Methods used to investigate in vivo kinetics of apoA-I include exogenous labeling with radioiodine and endogenous labeling with stable isotopically labeled amino acids. We report here a direct comparison of these methods to determine the in vivo kinetics of apoA-I in four normal subjects. Purified apoA-I was labeled with I-125, reassociated with autologous plasma, and injected into study subjects. At the same time, [C-13(6)]phenylalanine was administered as a primed constant infusion for up to 14 hours. The kinetic parameters of apoA-I were determined from the I-125-labeled apoA-I plasma curves. For the analysis of data from stable isotope studies, very low density lipoprotein (VLDL) apoB-100, VLDL apoB-4.8, and total apoA-I were isolated by ultracentrifugation and subsequent preparative NaDodSO4-PAGE, hydrolyzed, and derivatized. The tracer/tracee ratio was determined by gas chromatography-mass spectrometry. Monoexponential function analysis was used to determine the tracer/tracee curves of VLDL apoB-100 and VLDL apoB-48, and total apoA-I. The mean plateau tracer/tracee ratio of VLDL apoB-100 (primarily liver-derived) was 5.19%, whereas that of VLDL apoB-48 (intestinally derived) was only 3.74%. Using the VLDL apoB-100 plateau tracer/tracee ratio as the estimate of the precursor pool enrichment for apoA-I, the mean apoA-I residence time (RT) was 5.14 +/- 0.41 days, compared with 4.80 +/- 0.30 days for the exogenous labeling method. The apoA-I RTs using these two methods were highly correlated (r-0.874). We also used several different assumptions about the relative contribution of the liver and the intestine to the total plasma apoA-I pool and compared the kinetic parameters obtained with each of these assumptions to those obtained with the exogenous radiotracer method. The assumption that the liver contributed 90% of the total apoA-I pool resulted in the closest agreement between methods (RT 4.85 +/- 0.35 days by stable isotope). In addition, the mean RT of VLDL apoB-48 was 3.9 hours, significantly longer than that of VLDL apoB-100 of 1.9 hours. These data indicate that endogenous labeling of apoA-I by primed constant infusion using the VLDL apoB-100 plateau tracer/tracee ratio as the estimate of the precursor pool tracer/tracee ratio for apoA-I provides kinetic parameters that are highly comparable with those obtained by the exogenous labeling method. RP IKEWAKI, K (reprint author), NHLBI,MOLEC DIS BRANCH,BLDG 10,ROOM 7N117,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 49 TC 79 Z9 80 U1 0 U2 1 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD DEC PY 1993 VL 34 IS 12 BP 2207 EP 2215 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ML674 UT WOS:A1993ML67400018 PM 8301239 ER PT J AU QIN, J DELAGLIO, F LAMAR, GN BAX, A AF QIN, J DELAGLIO, F LAMAR, GN BAX, A TI DISTINGUISHING THE EFFECTS OF CROSS-CORRELATION AND J-COUPLING IN COSY SPECTRA OF PARAMAGNETIC PROTEINS SO JOURNAL OF MAGNETIC RESONANCE SERIES B LA English DT Note ID NUCLEAR-MAGNETIC-RESONANCE; RELAXATION; SPECTROSCOPY; CYTOCHROME-C'; ASSIGNMENT; PEROXIDASE; PHASE C1 UNIV CALIF DAVIS,DEPT CHEM,DAVIS,CA 95616. RP QIN, J (reprint author), NIDDKD,CLIN PHYS LAB,BETHESDA,MD 20892, USA. NR 15 TC 29 Z9 29 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1064-1866 J9 J MAGN RESON SER B JI J. Magn. Reson. Ser. B PD DEC PY 1993 VL 102 IS 3 BP 332 EP 336 DI 10.1006/jmrb.1993.1105 PG 5 WC Physics, Atomic, Molecular & Chemical SC Physics GA MU854 UT WOS:A1993MU85400012 ER PT J AU YOSHIKAWA, T ASANO, Y KOBAYASHI, I NAKASHIMA, T YAZAKI, T SUGA, S OZAKI, T WYATT, LS FRENKEL, N AF YOSHIKAWA, T ASANO, Y KOBAYASHI, I NAKASHIMA, T YAZAKI, T SUGA, S OZAKI, T WYATT, LS FRENKEL, N TI SEROEPIDEMIOLOGY OF HUMAN HERPESVIRUS-7 IN HEALTHY-CHILDREN AND ADULTS IN JAPAN SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE EXANTHEM SUBITUM; HUMAN HERPESVIRUS 6; HUMAN HERPESVIRUS 7; INDIRECT IMMUNOFLUORESCENCE ASSAY; NEUTRALIZATION TEST ID POLYMERASE CHAIN-REACTION; SALIVA; ANTIBODY; HHV-6; VIRUS AB The isolation of human herpesvirus 7 (HHV-7) from saliva and blood, and the prevalence of antibodies to the virus in healthy individuals were investigated in Japan. By cocultivating samples with phytohemagglutinin-P-stimulated cord blood mononuclear cells, HHV-7 was isolated from the saliva of 1 of 20 children and from 4 of 38 adults but not from their blood. The isolates were confirmed as closely related to RK strain of HHV-7, but not to U1102 (human herpesvirus 6, HHV-6 type A) or Z29 (HHV-6 type B) strains by restriction cleavage patterns of the DNA. The virus antibody of 330 healthy children and adults was measured with an indirect immunofluorescence assay, using one of our isolates (FG7-6). The positivity rate of antibody was 40% in the first 2 months of life, declined during the first 6 months, then gradually increased and was 45% at 1-4 years of age. It reached the highest level (60%) at 11-13 years of age and was maintained until the end of the third decade, then decreased thereafter. Additionally, no simultaneous rise in the antibody titers was observed in 7 virologica lly confirmed exanthem subitum patients. (C) 1993 Wiley-Liss, Inc. C1 FUJITA HLTH UNIV,SCH MED,DEPT PEDIAT,TOYOAKE,AICHI 47011,JAPAN. TOYOKAWA CITY HOSP,DEPT PEDIAT,TOYOKAWA,AICHI,JAPAN. SHOWA HOSP,DEPT PEDIAT,KONAN,AICHI,JAPAN. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. RI Asano, Yoshizo/F-6870-2012 NR 17 TC 80 Z9 81 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 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD DEC PY 1993 VL 41 IS 4 BP 319 EP 323 DI 10.1002/jmv.1890410412 PG 5 WC Virology SC Virology GA MJ717 UT WOS:A1993MJ71700011 PM 8106867 ER PT J AU MINTON, AP AF MINTON, AP TI MACROMOLECULAR CROWDING AND MOLECULAR RECOGNITION SO JOURNAL OF MOLECULAR RECOGNITION LA English DT Proceedings Paper CT Round Table Conference on Molecular Recognition CY JUL 22-24, 1993 CL PECS, HUNGARY SP HUNGARIAN ACAD SCI, PECS REG COMM, UNIV MED SCH PECS, BIOPHYS INST ID PROTEINS; CONSEQUENCES; VOLUME C1 NIDDK,BIOCHEM PHARMACOL LAB,PHYS BIOCHEM SECT,BETHESDA,MD 20892. NR 11 TC 38 Z9 38 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0952-3499 J9 J MOL RECOGNIT JI J. Mol. Recognit. PD DEC PY 1993 VL 6 IS 4 BP 211 EP 214 DI 10.1002/jmr.300060410 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NQ211 UT WOS:A1993NQ21100009 PM 7917416 ER PT J AU MACLEAN, PD AF MACLEAN, PD TI NATURES MIND - THE BIOLOGICAL ROOTS OF THINKING, EMOTIONS, SEXUALITY, LANGUAGE, AND INTELLIGENCE. - GAZZANIGA,MS SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review RP MACLEAN, PD (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD DEC PY 1993 VL 181 IS 12 BP 766 EP 767 DI 10.1097/00005053-199312000-00012 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA MN129 UT WOS:A1993MN12900011 ER PT J AU SAITO, K NOWAK, TS SUYAMA, K QUEARRY, BJ SAITO, M CROWLEY, JS MARKEY, SP HEYES, MP AF SAITO, K NOWAK, TS SUYAMA, K QUEARRY, BJ SAITO, M CROWLEY, JS MARKEY, SP HEYES, MP TI KYNURENINE PATHWAY ENZYMES IN BRAIN - RESPONSES TO ISCHEMIC BRAIN INJURY VERSUS SYSTEMIC IMMUNE ACTIVATION SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE KYNURENINE-3-HYDROXYLASE; INDOLEAMINE-2, 3-DIOXYGENASE; KYNURENINASE; 3-HYDROXYANTHRANILATE-3, 4-DIOXYGENASE; KYNURENINE AMINOTRANSFERASE; QUINOLINIC ACID; CEREBRAL ISCHEMIA; POKEWEED MITOGEN ID FLUID QUINOLINIC ACID; PERFORMANCE LIQUID-CHROMATOGRAPHY; CEREBROSPINAL-FLUID; RAT-BRAIN; 3-HYDROXYANTHRANILIC ACID; NEUROACTIVE KYNURENINES; TRYPTOPHAN-METABOLISM; HUNTINGTONS-DISEASE; REGIONAL BRAIN; SERUM AB Accumulation Of L-kynurenine and quinolinic acid (QUIN) in the brain occurs after either ischemic brain injury or after systemic administration of pokeweed mitogen. Although conversion of L-[C-13(6)]tryptophan to [C-13(6)]QUIN has not been demonstrated in brain either from normal gerbils or from gerbils given pokeweed mitogen, direct conversion in brain tissue does occur 4 days after transient cerebral ischemia. Increased activities of enzymes distal to indoleamine-2,3-dioxygenase may determine whether L-kynurenine is converted to QUIN. One day after 10 min of cerebral ischemia, the activities of kynureninase and 3-hydroxy-3,4-dioxygenase were increased in the hippocampus, but local QUIN levels and the activities of the indoleamine-2,3-dioxygenase and kynurenine-3-hydroxylase were unchanged. By days 2 and 4 after ischemia, however, the activities of all of these enzymes in the hippocampus as well as QUIN levels were significantly increased. Kynurenine aminotransferase activity in the hippocampus was unchanged on days 1 and 2 after ischemia but was decreased on day 4, at a time when local kynurenic acid levels were unchanged. A putative precursor of OUIN, [C-13(6)]anthranilic acid, was not converted to [C-13(6)]QUIN in the hippocampus of either normal or 4-day postischemic gerbils. Gerbil macrophages stimulated by endotoxin in vitro converted L-[C-13(6)]tryptophan to [C-13(6)]QUIN. Kinetic analysis of kynurenine-3-hydroxylase activity in the cerebral cortex of postischemic gerbils showed that V(max) increased, without changes in K(m). Systemic administration of pokeweed mitogen increased indoleamine-2,3-dioxygenase and kynureninase activities in the brain without significant changes in kynurenine-3-hydroxylase or 3-hydroxyanthranilate-3,4-dioxygenase activities. Increases in kynurenine-3-hydroxylase activity, in conjunction with induction of indoleamine-2,3-dioxygenase, kynureninase, and 3-hydroxyanthranilate-3,4-dioxygenase in macrophage infiltrates at the site of brain injury, may explain the ability of postischemic hippocampus to convert L-[C-13(6)]tryptophan to [C-13(6)]QUIN. C1 NIMH, CLIN SCI LAB,ANALYT BIOCHEM SECT,BLDG 10,ROOM 3D40, BETHESDA, MD 20892 USA. NIMH, CLIN PHARMACOL SECT, BETHESDA, MD 20892 USA. NINCDS, STROKE BRANCH, BETHESDA, MD 20892 USA. NR 59 TC 90 Z9 91 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 1993 VL 61 IS 6 BP 2061 EP 2070 DI 10.1111/j.1471-4159.1993.tb07443.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA MH022 UT WOS:A1993MH02200010 PM 8245962 ER PT J AU MANJI, HK ETCHEBERRIGARAY, R CHEN, G OLDS, JL AF MANJI, HK ETCHEBERRIGARAY, R CHEN, G OLDS, JL TI LITHIUM DECREASES MEMBRANE-ASSOCIATED PROTEIN-KINASE-C IN HIPPOCAMPUS - SELECTIVITY FOR THE ALPHA-ISOZYME SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE LITHIUM; PROTEIN KINASE-C; HIPPOCAMPUS; BIPOLAR AFFECTIVE DISORDER; MEMORY ID ELECTRON-MICROSCOPIC LOCALIZATION; INOSITOL PHOSPHOLIPID HYDROLYSIS; RAT-BRAIN; DOWN-REGULATION; PHORBOL ESTER; ADENYLATE-CYCLASE; PITUITARY-CELLS; RELEASE; EXPRESSION; AGONIST AB We investigated the effects of lithium on alterations in the amount and distribution of protein kinase C (PKC) in discrete areas of rat brain by using [H-3]phorbol 12,13-dibutyrate quantitative autoradiography as well as western blotting. Chronic administration of lithium resulted in a significant decrease in membrane-associated PKC in several hippocampal structures, most notably the subiculum and the CA1 region. In contrast, only modest changes in [H-3]phorbol 12,13-dibutyrate binding were observed in the various other cortical and subcortical structures examined. Immunoblotting using monoclonal anti-PKC antibodies revealed an isozyme-specific 30% decrease in hippocampal membrane-associated PKC alpha, in the absence of any changes in the labeling of either the beta(I/II) or gamma isozymes. These changes were observed only after chronic (4 week) treatment with lithium, and not after acute (5 days) treatment, suggesting potential clinical relevance. Given the critical role of PKC in regulating neuronal signal transduction, lithium's effects on PKC in the limbic system represent an attractive molecular mechanism for its efficacy in treating both poles of manic-depressive illness. In addition, the decreased hippocampal membrane-associated PKC observed in the present study offers a possible explanation for lithium-induced memo impairment. C1 NINCDS,BETHESDA,MD 20892. RP MANJI, HK (reprint author), NIMH,CLIN PHARMACOL SECT,BLDG 10,ROOM 2D46,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Olds, James/D-2867-2011; Chen, Guang/A-2570-2017 NR 62 TC 139 Z9 141 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 1993 VL 61 IS 6 BP 2303 EP 2310 DI 10.1111/j.1471-4159.1993.tb07474.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA MH022 UT WOS:A1993MH02200041 PM 8245981 ER PT J AU ERICKSON, JD EIDEN, LE AF ERICKSON, JD EIDEN, LE TI FUNCTIONAL IDENTIFICATION AND MOLECULAR-CLONING OF A HUMAN BRAIN VESICLE MONOAMINE TRANSPORTER SO JOURNAL OF NEUROCHEMISTRY LA English DT Note DE HUMAN VESICLE MONOAMINE TRANSPORTER TYPE-I; VACCINIA VIRUS SP6 BACTERIOPHAGE HYBRID EXPRESSION; DIGITONIN PERMEABILIZATION; RESERPINE; TETRABENAZINE; BIOGENIC AMINES; MPP(+) ID MEMBRANE; SYSTEM AB A vesicle monoamine transporter was functionally identified, molecularly cloned, and characterized from a human substantia nigra cDNA library. The ATP-dependent transport of 5-[H-3]hydroxytryptamine ([H-3]5-HT) by digitonin-permeabilized fibroblasts expressing the vesicle monoamine/H+ antiporter in culture exhibited a K(m) of 0,55 muM. Reserpine and tetrabenazine, inhibitors of two monoamine binding sites, effectively blocked [H-3]5-HT accumulation with K(i) values of 34 and 78 nM, respectively. Pretreatment of cells with as little as 1 0 nM reserpine in the presence of ATP abolished uptake. The rank order for substrate inhibition of [H-3]5-HT uptake for both the previously reported rat vMAT1 and the human transporter clone followed the order 5-HT > dopamine > epinephrine > norepinephrine > 1 -methyl-4-phenylpyridinium > 2-phenylethylamine > histamine. The virtually identical transport characteristics of rvMAT1 and hvMAT1 confirm the relevance of neuropharmacological studies of rat brain biogenic amine uptake and storage to human brain neurochemistry. RP ERICKSON, JD (reprint author), NIMH,CELL BIOL LAB,MOLEC NEUROSCI SECT,BLDG 36,ROOM 3A-17,BETHESDA,MD 20892, USA. OI Eiden, Lee/0000-0001-7524-944X NR 17 TC 122 Z9 124 U1 3 U2 5 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 1993 VL 61 IS 6 BP 2314 EP 2317 DI 10.1111/j.1471-4159.1993.tb07476.x PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA MH022 UT WOS:A1993MH02200043 PM 8245983 ER PT J AU INSEL, TR YOUNG, L WITT, DM CREWS, D AF INSEL, TR YOUNG, L WITT, DM CREWS, D TI GONADAL-STEROIDS HAVE PARADOXICAL EFFECTS ON BRAIN OXYTOCIN RECEPTORS SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE OXYTOCIN; TESTOSTERONE; VENTROMEDIAL NUCLEUS OF HYPOTHALAMUS; LATERAL SEPTUM ID LIGHT MICROSCOPIC AUTORADIOGRAPHY; VENTROMEDIAL HYPOTHALAMIC NUCLEUS; AFFINITY BINDING-SITES; RAT-BRAIN; GUINEA-PIG; FEMALE RATS; NEUROHYPOPHYSEAL HORMONES; OVARIAN-STEROIDS; VASOPRESSIN; LOCALIZATION AB Specific brain receptors for oxytocin have been described in several mammalian species. The distribution of these receptors differs greatly across species and in the rat, receptor binding in specific brain regions appears to depend upon gonadal steroids. This study used in vitro receptor autoradiography to examine the effects of testosterone on oxytocin receptor binding in the mouse forebrain. Three groups of male mice were compared: castrates treated with blank capsules, castrates treated with testosterone filled capsules, and intact males. Irrespective of steroid treatment, the distribution of oxytocin receptors in mouse forebrain differed markedly from patterns previously described in the rat. In addition to these species differences in receptor distribution, testosterone had effects in the mouse which differed from the induction of receptors previously reported in the rat. In the mouse ventromedial nucleus of the hypothalamus, binding in the untreated castrate males was approximately double that observed in either the intact or the testosterone-treated castrates. In other regions of the mouse brain, such as the intermediate zone of the lateral septum, binding to oxytocin receptors was increased with testosterone treatment. These results suggest that the brain oxytocin receptor varies across species not only in its distribution but also in its regional regulation by gonadal steroids. These apparently paradoxical changes in oxytocin receptor binding may result from either direct or indirect effects of gonadal steroids in mouse brain. C1 UNIV TEXAS,DEPT ZOOL,AUSTIN,TX 78712. RP INSEL, TR (reprint author), NIMH,NIHAC,NEUROPHYSIOL LAB,POB 608,POOLESVILLE,MD 20837, USA. FU NIMH NIH HHS [NIMH00135, NIMH41770] NR 63 TC 70 Z9 71 U1 1 U2 5 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD DEC PY 1993 VL 5 IS 6 BP 619 EP 628 DI 10.1111/j.1365-2826.1993.tb00531.x PG 10 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA MM533 UT WOS:A1993MM53300004 PM 8680433 ER PT J AU CAINE, ED AF CAINE, ED TI SHOULD AGING-ASSOCIATED COGNITIVE DECLINE BE INCLUDED IN DSM-IV SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID OLDER ADULTS; MEMORY COMPLAINTS; DEMENTIA RP CAINE, ED (reprint author), UNIV ROCHESTER,MED CTR,NIMH,CLIN RES CTR STUDY PSYCHOPATHOL ELDERLY,300 CRITTENDEN BLVD,ROCHESTER,NY 14642, USA. FU NIMH NIH HHS [MH40381] NR 19 TC 32 Z9 33 U1 0 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD WIN PY 1993 VL 5 IS 1 BP 1 EP 5 PG 5 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA KK041 UT WOS:A1993KK04100001 PM 8428128 ER PT J AU CAINE, ED AF CAINE, ED TI AMNESIC DISORDERS SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID TRANSIENT GLOBAL AMNESIA; PROGNOSIS RP CAINE, ED (reprint author), UNIV ROCHESTER,MED CTR,NIMH,CLIN RES CTR,300 CRITTENDEN BLVD,ROCHESTER,NY 14642, USA. FU NIMH NIH HHS [MH40381] NR 21 TC 2 Z9 2 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD WIN PY 1993 VL 5 IS 1 BP 6 EP 8 PG 3 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA KK041 UT WOS:A1993KK04100002 PM 8428137 ER PT J AU MAPOU, RL LAW, WA MARTIN, A KAMPEN, D SALAZAR, AM RUNDELL, JR AF MAPOU, RL LAW, WA MARTIN, A KAMPEN, D SALAZAR, AM RUNDELL, JR TI NEUROPSYCHOLOGICAL PERFORMANCE, MOOD, AND COMPLAINTS OF COGNITIVE AND MOTOR DIFFICULTIES IN INDIVIDUALS INFECTED WITH THE HUMAN-IMMUNODEFICIENCY-VIRUS SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID HOMOSEXUAL MEN; AIDS AB Seventy-nine military medical beneficiaries infected with human immunodeficiency virus (HIV+) and 27 HIV-seronegative control subjects (HIV-) completed a neuropsychological evaluation and a semistructured interview inquiring about difficulties in function. More HIV+ than HIV- subjects reported difficulties. HIV+ subjects reporting difficulties were significantly more likely to be deficient on attention, response speed, motor function, and memory than those not reporting difficulties. Findings for early-stage HIV+ subjects were similar. HIV+ individuals who complained of difficulties reported depression and anxiety symptoms significantly more frequently than those who did not complain, but these symptoms were not related to neuropsychological performance. Complaints of difficulties by HIV+ individuals may reflect either actual neuropsychological deficiency or mood disturbance, but the effects of each appear to be independent. C1 NIMH,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. WALTER REED ARMY INST RES,WASHINGTON,DC 20307. RP MAPOU, RL (reprint author), HENRY M JACKSON FDN ADVANCEMENT MIL MED,MIL MED CONSORTIUM APPL RETROVIRAL RES,1 TAFT COURT,ROCKVILLE,MD 20850, USA. RI martin, alex/B-6176-2009 NR 35 TC 50 Z9 50 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD WIN PY 1993 VL 5 IS 1 BP 86 EP 93 PG 8 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA KK041 UT WOS:A1993KK04100014 PM 8428141 ER PT J AU STEINER, H GERFEN, CR AF STEINER, H GERFEN, CR TI COCAINE-INDUCED C-FOS MESSENGER-RNA IS INVERSELY RELATED TO DYNORPHIN EXPRESSION IN STRIATUM SO JOURNAL OF NEUROSCIENCE LA English DT Article DE C-FOS; DYNORPHIN, SUBSTANCE-P; ENKEPHALIN; COCAINE; STRIATUM; DOPAMINE; KAPPA-RECEPTOR ID KAPPA-OPIOID RECEPTOR; IMMEDIATE-EARLY GENES; RAT SPINAL-CORD; SUBSTANCE-P; ADENYLATE-CYCLASE; DOPAMINE UPTAKE; STRIATOPALLIDAL NEURONS; DIFFERENTIALLY ALTERS; MATRIX COMPARTMENTS; OPIATE RECEPTORS AB The effects of the indirect dopamine receptor agonist cocaine in the striatum on levels of mRNAs of the immediate-early gene c-fos and the neuropeptides dynorphin, substance P, and enkephalin were analyzed with quantitative in situ hybridization histochemistry. Both single (acute) and repeated (twice a day for 4 d) systemic injections of cocaine (3.75-30 mg/kg) to rats resulted in dose-dependent, regionally specific elevations of mRNA expression in striatal neurons. A single drug treatment elevated c-fos mRNA expression, whereas repeated treatments resulted in little c-fos expression but elevated dynorphin mRNA levels. Both the regional and temporal patterns of gene expression revealed an inverse relationship between dynorphin and c-fos expression. This relationship was examined in a time course experiment in which cocaine (30 mg/kg) was administered for 1, 2, 3 or 4 d. Basal levels of dynorphin expression were relatively high in the ventral striatum, including the nucleus accumbens, a ventrolateral region, and an area along the medial bank of the striatum. A single injection of cocaine induced c-fos mRNA in striatal areas with low basal expression of dynorphin. Thus, c-fos mRNA induction was highest in the dorsal central striatum, where basal dynorphin mRNA levels were lowest. In this region, dynorphin mRNA expression increased on subsequent treatment days parallel to diminished c-fos mRNA induction. Changes in substance P mRNA levels appeared to match directly both the temporal and regional patterns of c-fos induction. Enkephalin mRNA expression was altered, but only slightly, by these cocaine treatments. Statistical analysis of the regional patterns of basal and altered mRNA levels shows a unique inverse relationship between basal dynorphin expression and c- fos induction by cocaine. Further evidence of this relationship is provided by the dose-dependent blockade of cocaine-induced c-fos expression by spiradoline, a dynorphin agonist. Together, these results suggest that the restricted regional pattern of cocaine-induced c-fos expression is related, in part, to the basal level of dynorphin expression, and that cocaine treatment elevates dynorphin expression in striatal regions with a strong c-fos response, thereby limiting subsequent c-fos induction by cocaine. These findings lead to the hypothesis that dynorphin acts to regulate the responsiveness of striatal neurons to dopamine stimulation. C1 NIMH,NEUROANAT SECT,BLDG 36,ROOM 2D-10,BETHESDA,MD 20892. NR 64 TC 213 Z9 213 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC PY 1993 VL 13 IS 12 BP 5066 EP 5081 PG 16 WC Neurosciences SC Neurosciences & Neurology GA MN040 UT WOS:A1993MN04000005 PM 7504719 ER PT J AU BONDY, C LEE, WH AF BONDY, C LEE, WH TI CORRELATION BETWEEN INSULIN-LIKE GROWTH-FACTOR (IGF) BINDING PROTEIN-5 AND IGF-1 GENE-EXPRESSION DURING BRAIN-DEVELOPMENT SO JOURNAL OF NEUROSCIENCE LA English DT Article DE IGF-1; IGF-1 RECEPTOR; MESSENGER RNA; CEREBELLUM; GERMINAL ZONE ID FACTOR-I; RAT-BRAIN; CEREBROSPINAL-FLUID; LOCALIZATION; RECEPTORS; AUTORADIOGRAPHY; MATURATION; DISTINCT; PATTERN AB Insulin-like growth factor (IGF)-binding proteins (IGFBPs) potently modulate the interactions of IGF-I and -II with the IGF-I receptor. Previous studies have shown that IGFBP2 gene expression is localized in astroglia, where it is anatomically and temporally coordinated with neuronal IGF-I expression during postnatal brain development. The present study shows that IGFBP5 gene expression is also highly abundant during brain development and also demonstrates significant spatiotemporal correlation with IGF-I, but exhibits a neuroanatomical distribution that is entirely distinct from IGFBP2. IGFBP5 and IGF-I mRNAs are synchronously coexpressed in principal neurons of sensory relay systems, including the olfactory bulb, medial and dorsal lateral geniculate bodies, and ventral tier, cochlear, lemniscal, and vestibular nuclei. They are also transiently coexpressed in principal neurons of the anterodorsal nucleus, but IGF-I mRNA disappears from this structure shortly after birth, while IGFBP5 mRNA remains highly abundant here in the adult. IGFBP5 and IGF-I gene expression demonstrate a temporally coordinated laminar association in the developing cerebellar cortex and hippocampal formation. IGF-I mRNA is concentrated in Purkinje cells, while IGFBP5 mRNA is localized in the external germinal zone in the developing cerebellar cortex. IGFBP5 mRNA is transiently expressed in the retrosplenial and cingulate cortex, subiculum, Ammon's horn, and amygdala, while IGF-I mRNA is contemporaneously localized in large interneurons distributed throughout the hippocampal formation. IGFBP5 mRNA is localized in the lateral ventricular germinal zone at birth and remains in the subventricular zone into maturity. It is also detected in forebrain white matter tracts and olfactory nerve from the second week after birth into maturity. Thus IGFBP5, in addition to IGFBP2, may be a significant determinant of IGF action in the brain. Colocalization in some sites and paralocalization with IGF-I in other sites suggests the potential for autocrine and paracrine interaction between the binding protein and IGF-I in different settings. Arguments are advanced suggesting a role for IGFBPs in the targeting of IGF action to specific cell addresses during brain development. RP BONDY, C (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N262,BETHESDA,MD 20892, USA. NR 26 TC 99 Z9 101 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC PY 1993 VL 13 IS 12 BP 5092 EP 5104 PG 13 WC Neurosciences SC Neurosciences & Neurology GA MN040 UT WOS:A1993MN04000007 PM 7504720 ER PT J AU ROBINSON, JK CRAWLEY, JN AF ROBINSON, JK CRAWLEY, JN TI INTRASEPTAL GALANIN POTENTIATES SCOPOLAMINE IMPAIRMENT OF DELAYED-NONMATCHING-TO-SAMPLE SO JOURNAL OF NEUROSCIENCE LA English DT Article DE ACH; COEXISTENCE; LEARNING; MEDIAL SEPTUM; MEMORY; MICROINJECTION; NEUROPEPTIDE; SEPTOHIPPOCAMPAL PATHWAY; RETENTION ID CENTRAL NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; VENTRAL HIPPOCAMPUS; NUCLEUS BASALIS; CHOLINERGIC SYSTEM; MEMORY; IMMUNOREACTIVITY; RAT; ACETYLCHOLINE; FOREBRAIN AB Galanin coexists with ACh in the basal forebrain and medial septal region. The present study investigated the interactions of the muscarinic receptor antagonist scopolamine and the neuropeptide galanin on an operant spatial delayed non-matching to sample task (DNMTS) in rats. Scopolamine administered both intraperitoneally and microinjected into the medial septum impaired performance on DNMTS. Galanin administered alone into the medial septum did not disrupt DNMTS, but potentiated the disruptive effects of intraperitoneal administered scopolamine. These findings raise the possibility that endogenous galanin may exacerbate cognitive impairments associated with forebrain cholinergic deficits. RP ROBINSON, JK (reprint author), NIMH,EXPTL THERAPEUT BRANCH,BEHAV NEUROPHARMACOL SECT,BLDG 10,ROOM 4N214,BETHESDA,MD 20892, USA. NR 36 TC 41 Z9 42 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC PY 1993 VL 13 IS 12 BP 5119 EP 5125 PG 7 WC Neurosciences SC Neurosciences & Neurology GA MN040 UT WOS:A1993MN04000009 PM 7504722 ER PT J AU MEUNIER, M BACHEVALIER, J MISHKIN, M MURRAY, EA AF MEUNIER, M BACHEVALIER, J MISHKIN, M MURRAY, EA TI EFFECTS ON VISUAL RECOGNITION OF COMBINED AND SEPARATE ABLATIONS OF THE ENTORHINAL AND PERIRHINAL CORTEX IN RHESUS-MONKEYS SO JOURNAL OF NEUROSCIENCE LA English DT Article DE MEMORY; HIPPOCAMPUS; AMYGDALA; MEDIAL TEMPORAL LOBE; DELAYED NONMATCHING-TO-SAMPLE TASK; NONHUMAN PRIMATE ID AREA 35 CORTICES; HIPPOCAMPAL-FORMATION; TEMPORAL POLE; BRAIN-LESIONS; AMYGDALA; MEMORY; CONNECTIONS; PROJECTIONS; ORGANIZATION; IMPAIRMENT AB Performance on visual delayed nonmatching-to-sample was assessed in rhesus monkeys with combined and separate ablations of the perirhinal and entorhinal cortex, as well as in unoperated controls. Combined (i.e., rhinal cortex) lesions yielded a striking impairment on this task, one almost as severe as that seen after combined amygdalohippocampal removals that included some of this subjacent cortex (Mishkin, 1978; Murray and Mishkin, 1984). Ablations of the perirhinal cortex alone produced a deficit nearly as severe as that found after rhinal cortex lesions, whereas ablations of the entorhinal cortex alone produced only a mild deficit. Contrary to the conclusion from an earlier study (Murray and Mishkin, 1 986), the present results demonstrate not only that damage limited to the rhinal cortex is sufficient to produce a severe loss in visual recognition, but also that such damage leads to a far greater loss than damage to any other single structure in the medial part of the tem oral lobe. C1 NIMH, NEUROPSYCHOL LAB, BLDG 49, ROOM 1B80, BETHESDA, MD 20892 USA. RI MEUNIER, Martine/C-2611-2015; OI MEUNIER, Martine/0000-0002-9380-9372; Murray, Elisabeth/0000-0003-1450-1642 NR 55 TC 646 Z9 649 U1 1 U2 20 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC PY 1993 VL 13 IS 12 BP 5418 EP 5432 PG 15 WC Neurosciences SC Neurosciences & Neurology GA MN040 UT WOS:A1993MN04000035 PM 8254384 ER PT J AU BHARUCHA, VA PEDEN, KWC SUBACH, BR NARAYANAN, V TENNEKOON, GI AF BHARUCHA, VA PEDEN, KWC SUBACH, BR NARAYANAN, V TENNEKOON, GI TI CHARACTERIZATION OF THE CIS-ACTING ELEMENTS OF THE MOUSE MYELIN P2 PROMOTER SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE DELETION MUTANTS; SILENCER; CAMP RESPONSIVE ELEMENTS; CAAT ENHANCER BINDING PROTEIN ID CULTURED SCHWANN-CELLS; CENTRAL NERVOUS-SYSTEM; BASIC-PROTEIN GENE; CYCLIC-AMP; PERIPHERAL MYELIN; BINDING-PROTEIN; EXPRESSION; TRANSCRIPTION; DIFFERENTIATION; IDENTIFICATION AB Myelin P2 is a basic protein of an apparent molecular weight of 14,800. Expression Of P2 has been found largely in the cytosol of Schwann cells in the peripheral nervous system. Although the function of P2 is unknown, its striking homology to a family of fatty acid binding proteins has led to the idea that P2 may function as a fatty acid transport molecule. To investigate the DNA elements that control the expression of P2, sequences 5' to the coding region were cloned upstream of the cat reporter gene. A series of 3' and 5' promoter mutants was constructed and their activity determined following transfection into secondary Schwann cells and the MT4H1 Schwann cell line. Using this strategy, we have identified a 217 bp silencer region and a 142 bp positive regulatory region. In addition, we have localized the 5' flanking sequences in the promoter that are responsive to cAMP induction and to the transcription factor CCAAT/enhancer binding protein (C/EBP). (C) 1993 Wiley-Liss, Inc. C1 UNIV MICHIGAN,MED CTR,DEPT PEDIAT,PEDIAT NEUROL SECT,R6060 KRESGE 2,BOX 0570,ANN ARBOR,MI 48109. UNIV PITTSBURGH,DEPT PEDIAT,PITTSBURGH,PA 15260. UNIV MICHIGAN,MED CTR,DEPT NEUROL,PEDIAT NEUROL SECT,ANN ARBOR,MI 48109. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. OI Narayanan, Vinodh/0000-0002-0658-3847 FU NINDS NIH HHS [R01 NS 29710-01] NR 38 TC 15 Z9 15 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD DEC 1 PY 1993 VL 36 IS 5 BP 508 EP 519 DI 10.1002/jnr.490360503 PG 12 WC Neurosciences SC Neurosciences & Neurology GA MH743 UT WOS:A1993MH74300002 PM 7511696 ER PT J AU JOHN, CS BOWEN, WD SAGA, T KINUYA, S VILNER, BJ BAUMGOLD, J PAIK, CH REBA, RC NEUMANN, RD VARMA, VM MCAFEE, JG AF JOHN, CS BOWEN, WD SAGA, T KINUYA, S VILNER, BJ BAUMGOLD, J PAIK, CH REBA, RC NEUMANN, RD VARMA, VM MCAFEE, JG TI A MALIGNANT-MELANOMA IMAGING AGENT - SYNTHESIS, CHARACTERIZATION, IN-VITRO BINDING AND BIODISTRIBUTION OF IODINE-125-(2-PIPERIDINYLAMINOETHYL)4-IODOBENZAMIDE SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article ID MONOCLONAL-ANTIBODY; RECEPTORS AB In order to develop improved radiopharmaceuticals for imaging malignant melanoma, we have synthesized and characterized I-125- and I-131-labeled (2-piperidinylaminoethyl) 4-iodobenzamide (PAB). In vitro binding profiles of IPAB and N-(2-diethylaminoethyl) 4-iodobenzamide (IDAB, a structurally related analog of IPAB) for a variety of neurotransmitter receptors suggested that both IPAB and IDAB possessed a high sigma-1 affinity and a low affinity for sigma-e sites. In vitro homologous competition binding studies of [(125)l]PAB with human malignant melanoma cell A2058 showed that the tracer was bound to the cells with a high affinity (Ki = 6.0 nM) and that the binding was saturable. Biodistribution studies in nude mice implanted with human malignant melanoma xenografts showed good tumor uptake (3.87% ID/g at 1 hr, 2.91% ID/g at 6 hr and 1.02% ID/g at 24 hr) of [(125)l]PAB. High tumor-to-nontarget organ ratios were obtained at 24 hr postinjection. Tumor-to-blood, liver, muscle, lung, intestines, heart and brain ratios at 24 hr were 17.80, 3.88, 94.58, 14.29, 10.87, 37.07 and 90.01, respectively. Tumor imaging with [I-131]PAB in a nude mice model xenografted with human malignant melanoma at 24 hr clearly delineated the tumor with very little activity in any other organ. These results demonstrate that sigma-1 receptors could be used as external markers for malignant melanoma. C1 NIDDKDNM,MED CHEM LAB,BETHESDA,MD. RP JOHN, CS (reprint author), GEORGE WASHINGTON UNIV,MED CTR,RADIOPHARMACEUT CHEM SECT,662 ROSS HALL,2300 I ST NW,WASHINGTON,DC 20037, USA. NR 24 TC 98 Z9 99 U1 0 U2 3 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD DEC PY 1993 VL 34 IS 12 BP 2169 EP 2175 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA MK579 UT WOS:A1993MK57900029 PM 8254405 ER PT J AU RESNICK, SM KARP, JS TURETSKY, B GUR, RE AF RESNICK, SM KARP, JS TURETSKY, B GUR, RE TI COMPARISON OF ANATOMICALLY-DEFINED VERSUS PHYSIOLOGICALLY-BASED REGIONAL LOCALIZATION - EFFECTS ON PET-FDG QUANTITATION SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL GLUCOSE-UTILIZATION; F-18 FLUORODEOXYGLUCOSE; BRAIN; IMAGES AB The potential of anatomic imaging to improve the quantitative accuracy of functional brain imaging through refined regional definition is widely accepted. However, there are little data addressing the impact of approach to regional localization on quantitation of metabolic images in the absence of gross structural pathology. We compared MRI-based versus PET-based approaches to the analysis of PET F-18-fluorodeoxyglucose (FDG) images using a standard adjustable template based on simple geometric regions. For the MRI-based approach, templates and individual regions were adjusted to each individual's anatomy, whereas the PET-based definition involved only global proportional adjustment of the standard templates. Metabolic rates for glucose and volume-to-whole brain ratios were determined by two operators for 78 volumes of interest in five subjects. Pairwise correlations indicated high interoperator agreement for each approach and high intraoperator agreement for MRI-based Versus PET-based metabolic values. The stability of the metabolic rates and ratios among operators and analysis approaches was supported by low coefficients of variation across measurements and small average differences in paired comparisons. Thus, within the current spatial resolution of PET imaging, quantitation of metabolic images is relatively robust to image analysis approach in the absence of gross structural abnormality. To take advantage of the greater quantitative accuracy promised by high-resolution anatomic and functional imaging, more refined delineation of anatomic images will be necessary. C1 UNIV PENN,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. UNIV PENN,DEPT RADIOL,PHILADELPHIA,PA 19104. RP RESNICK, SM (reprint author), NIA,GRC,PERSONAL & COGNIT LAB,ROOM 2-C-14,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. FU NIMH NIH HHS [NIMH MH 43740, NIMH MH 48539, NIMH MHCRC 43880] NR 18 TC 34 Z9 34 U1 1 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD DEC PY 1993 VL 34 IS 12 BP 2201 EP 2207 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA MK579 UT WOS:A1993MK57900036 PM 8254412 ER PT J AU OBRIEN, KO ALLEN, LH QUATROMONI, P SIUCALDERA, ML VIEIRA, NE PEREZ, A HOLICK, MF YERGEY, AL AF OBRIEN, KO ALLEN, LH QUATROMONI, P SIUCALDERA, ML VIEIRA, NE PEREZ, A HOLICK, MF YERGEY, AL TI HIGH-FIBER DIETS SLOW BONE TURNOVER IN YOUNG MEN BUT HAVE NO EFFECT ON EFFICIENCY OF INTESTINAL CALCIUM-ABSORPTION SO JOURNAL OF NUTRITION LA English DT Article DE CALCIUM; KINETICS; DIETARY FIBER; VITAMIN-D; HUMANS ID VITAMIN-D DEFICIENCY; ISOTOPIC TRACERS; WHEAT FIBER; TIME; 1,25-DIHYDROXYVITAMIN-D3; 25-HYDROXYVITAMIN-D; METABOLISM; PLASMA; IRON; LIFE AB Dietary fiber reduces the absorption of dietary calcium from a meal, but its impact on calcium kinetics is unknown. We therefore evaluated the effects of a high fiber diet on calcium balance and kinetics and on calcium-regulating hormones. Seven young men each participated in two 23-d experiments. In the low fiber period the controlled diet provided 6.5 g fiber/d and 530 mg calcium/d. In the high fiber period fiber was increased to 31.3 g/d and calcium to 586 mg/d by substituting high fiber cereal. Measured between d 7 and 12 of each period, the high fiber diet significantly lowered the apparent absorption of calcium (from 60.6 +/- 23.8% to 37.1 +/- 26.5%) and reduced calcium balance, although balance remained positive overall. Fiber had no effect on serum total or ultrafiltrable calcium, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D or parathyroid hormone concentrations measured on d 1, 7, 12 and 20. Calcium kinetics was studied between d 17 and 23 by administering oral Ca-44 and intravenous Ca-42 to fasting subjects. Fractional absorption of calcium in the fasting state was unaffected by fiber. However, during the high fiber period, subjects had significantly lower bone accretion, resorption and turnover rates, and calcium flow to bone from the exchangeable pool than during the low fiber period. We conclude that the fiber-induced reduction in calcium absorption slowed down bone calcium turnover but did not increase the efficiency of intestinal absorption. C1 BOSTON UNIV,SCH MED,GEN CLIN RES CTR,BOSTON,MA 02118. UNIV CONNECTICUT,DEPT NUTR SCI,STORRS,CT 06269. RP OBRIEN, KO (reprint author), NIH,METAB ANAL & MASS SPECT SECT,9000 ROCKVILLE PIKE,BLDG 10,BETHESDA,MD 20892, USA. FU NCRR NIH HHS [MOIRR0533] NR 31 TC 13 Z9 13 U1 0 U2 4 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD DEC PY 1993 VL 123 IS 12 BP 2122 EP 2128 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA ML888 UT WOS:A1993ML88800011 PM 8263606 ER PT J AU FERRETTI, A FLANAGAN, VP JUDD, JT NAIR, PP TAYLOR, PR AF FERRETTI, A FLANAGAN, VP JUDD, JT NAIR, PP TAYLOR, PR TI FISH-OIL SUPPLEMENTATION REDUCES EXCRETION OF 2,3-DINOR-6-OXO-PGF1-ALPHA AND THE 11-DEHYDROTHROMBOXANE B(2)/2,3-DINOR-6-OXO-PGF1-ALPHA EXCRETION RATIO IN ADULT MEN SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article DE N-3 FATTY ACIDS; PROSTACYCLIN; THROMBOXANE-TO-PROSTACYCLIN RATIO; IN-VIVO SYNTHESIS; URINARY EXCRETION ID DIETARY EICOSAPENTAENOIC ACID; PROSTACYCLIN PRODUCTION; PLATELET-FUNCTION; ARACHIDONIC-ACID; METABOLISM; PROSTAGLANDIN-I3; EICOSANOIDS; INVIVO AB Dietary supplementation with a fish oil concentrate (FOC) reduced the endogenous synthesis of prostacyclin (PGI2), as measured by the excretion of its major urinary catabolite, 2,3-dinor-6-oxo-PGF1alpha (PGI2-M). Thirty-four healthy men (24-57 years old) were given controlled diets and supplements that provided 40% of the energy from fat and a minimum of 22 mg/d of alpha-tocopherol for two consecutive experimental periods of 10 weeks each. During the experimental periods, the men received capsules containing 15 g/d of a placebo oil (PO) (period 1) or 15 g/d of the FOC (period 2). In addition to the PO or FOC, capsules contained 1 mg of alpha-tocopherol per g of fat as an antioxidant. The average daily excretion of PGI2-M during the last week of FOC supplementation (period 2) was 22% less (P = 0.0001) than at the end of the first period. These results are at variance with those reported in comparable human studies conducted by other investigators during the middle and late 1980s. A 20% reduction (P = 0.003) in the 11-dehydrothromboxane B2 to 2,3-dinor-6-oxo-PGF1alpha excretion ratio at the end of period 2 in this study demonstrates that a shift of the n-6 to n-3 polyunsaturated fatty acid ratio from 12.5 to 2.3 brings about a substantial modulation of the eicosanoid system. C1 NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. RP FERRETTI, A (reprint author), USDA ARS,BELTSVILLE AGR RES CTR,LIPID NUTR LAB,BLDG 308,ROOM 122,BARC E,10300 BALTIMORE AVE,BELTSVILLE,MD 20705, USA. NR 23 TC 9 Z9 9 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0955-2863 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD DEC PY 1993 VL 4 IS 12 BP 695 EP 698 DI 10.1016/0955-2863(93)90109-A PG 4 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA MJ979 UT WOS:A1993MJ97900005 ER PT J AU HOLTON, JB DELACRUZ, F LEVY, HL AF HOLTON, JB DELACRUZ, F LEVY, HL TI GALACTOSEMIA - THE URIDINE-DIPHOSPHATE GALACTOSE DEFICIENCY-URIDINE TREATMENT CONTROVERSY SO JOURNAL OF PEDIATRICS LA English DT Article ID GLUCOSE C1 NICHHD, BETHESDA, MD 20892 USA. CHILDRENS HOSP MED CTR, STATE LAB INST, BOSTON, MA 02115 USA. RP HOLTON, JB (reprint author), SOUTHMEAD GEN HOSP, BRISTOL BS10 5NB, AVON, ENGLAND. NR 22 TC 18 Z9 18 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD DEC PY 1993 VL 123 IS 6 BP 1009 EP 1014 DI 10.1016/S0022-3476(05)80404-4 PG 6 WC Pediatrics SC Pediatrics GA MK827 UT WOS:A1993MK82700027 PM 8229508 ER PT J AU DYKSTRA, KH ARYA, A ARRIOLA, DM BUNGAY, PM MORRISON, PF DEDRICK, RL AF DYKSTRA, KH ARYA, A ARRIOLA, DM BUNGAY, PM MORRISON, PF DEDRICK, RL TI MICRODIALYSIS STUDY OF ZIDOVUDINE (AZT) TRANSPORT IN RAT-BRAIN SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID AIDS-RELATED COMPLEX; CEREBROSPINAL-FLUID; QUANTITATIVE MICRODIALYSIS; CONTINUOUS-INFUSION; 3'-AZIDO-3'-DEOXYTHYMIDINE; PHARMACOKINETICS; PHOSPHORYLATION; INVITRO; INVIVO; CLEARANCES AB The concentration profiles of [C-14]3'-azido-3'-deoxythymidine (AZT) emanating from an acutely implanted microdialysis probe were measured in rat caudate putamen by quantitative autoradiography for infusions of 14 min and 1 and 2 h. A mathematical model which simulated diffusive solute transport, unaffected by the processes of microvascular exchange or tissue metabolism, did not fit the observed concentration profiles. Chromatographic analysis of brain homogenates for metabolites of AZT showed that the rate of metabolic transformation was not large enough to affect transport of the drug through the brain tissue. A model simulating the effect of microvascular exchange on the diffusion profiles fit the observed concentration profiles and the transient change in the dialysate extraction fraction. This analysis yielded an estimated tissue elimination rate constant for microvascular exchange of K(el) = 0.01 3 ml/(g . min) and an intra- to extracellular partition coefficient of K(pi) = 1.04. Inclusion of probenecid in the dialysate, together with an i.p. injection, led to a substantial increase in the diffusion distance of the labeled AZT from the microdialysis probe, suggesting at least a 4-fold decrease in the microvascular exchange rate constant. These results imply that AZT is actively transported out of the brain parenchyma to the microvasculature and that this active transport mechanism is responsible for the limited central nervous system penetration of systemically administered AZT, in spite of its high lipid solubility. C1 NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENT PROGRAM,BLDG 13,BETHESDA,MD 20892. NIMH,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. NR 40 TC 70 Z9 70 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 1993 VL 267 IS 3 BP 1227 EP 1236 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MQ488 UT WOS:A1993MQ48800032 PM 8263784 ER PT J AU BUTELMAN, ER NEGUS, SS AL, Y DECOSTA, BR WOODS, JH AF BUTELMAN, ER NEGUS, SS AL, Y DECOSTA, BR WOODS, JH TI KAPPA-OPIOID ANTAGONIST EFFECTS OF SYSTEMICALLY ADMINISTERED NOR-BINALTORPHIMINE IN A THERMAL ANTINOCICEPTION ASSAY IN RHESUS-MONKEYS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID GUINEA-PIG BRAIN; BINDING-SITES; BETA-FUNALTREXAMINE; OPIATE RECEPTORS; ANALGESIC ACTIVITY; SELECTIVE AGONIST; SQUIRREL-MONKEY; MU-RECEPTOR; RAT; PEPTIDES AB The effects of subcutaneously administered nor-binaltorphimine (nor-BNI; 1.0 and 3.2 mg/kg) were examined in the warm-water (50-degrees-C and 55-degrees-C) tail-withdrawal assay in rhesus monkeys (n = 3). Nor-BNI alone produced variable antinociceptive effects in 50-degrees-C water up to 3.5 hr after administration but was completely ineffective against the 55-degrees-C stimulus. Pretreatment with nor-BNI under conditions where it was devoid of antinociceptive effects produced rightward shifts in dose-effect curves for the kappa opioid agonist U50,488 for as long as 14 and 21 days after 1.0 and 3.2 mg/kg of nor-BNI, respectively. Under conditions when U50,488 dose-effect curves were shifted, nor-BNI (3.2 mg/kg) also caused rightward shifts in the antinociceptive dose-effect curves of the kappa agonist U69,593 but not in those of the mu agonist alfentanil or the kappa agonists [5R-(5,7,8,beta)]N-methyl-N-[7-(l-pirrolidinyl)l-oxaspiro [4,5)dec-8-yl]4-benzofuranacetamide, bremazocine, ethylketocyclazocine and Mr2033. It is concluded that under the present conditions, nor-BNI acts as a selective kappa opioid antagonist with an extremely long duration of action. These findings are also consistent with the notion that nor-BNI may antagonize only compounds acting at a subtype of kappa opioid receptor. C1 UNIV MICHIGAN,DEPT PSYCHOL,ANN ARBOR,MI 48109. NIDDKD,BETHESDA,MD. RP BUTELMAN, ER (reprint author), UNIV MICHIGAN,DEPT PHARMACOL,6322 MED SCI 1,ANN ARBOR,MI 48109, USA. FU NIDA NIH HHS [DA-00254] NR 51 TC 80 Z9 82 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 1993 VL 267 IS 3 BP 1269 EP 1276 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MQ488 UT WOS:A1993MQ48800038 PM 8263790 ER PT J AU SANNERUD, CA MARLEY, RJ SERDIKOFF, SL ALASTRA, AJG COHEN, C GOLDBERG, SR AF SANNERUD, CA MARLEY, RJ SERDIKOFF, SL ALASTRA, AJG COHEN, C GOLDBERG, SR TI TOLERANCE TO THE BEHAVIORAL-EFFECTS OF CHLORDIAZEPOXIDE - PHARMACOLOGICAL AND BIOCHEMICAL SELECTIVITY SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID D-AMPHETAMINE; BENZODIAZEPINE LIGANDS; CONTINGENT TOLERANCE; AUGMENTED TOLERANCE; CHRONIC DIAZEPAM; CROSS-TOLERANCE; RATS; ETHANOL; MORPHINE; SUBSENSITIVITY AB There is a dynamic interaction between a drug's pharmacological effects and the behavioral context in which it is administered. The present study evaluated the influence of behavioral processes on the development of tolerance and cross-tolerance to the rate-decreasing effects of chlordiazepoxide in rats. Sprague-Dawley rats responded under a fixed-ratio 30 schedule of food delivery. Different groups of rats received 18 mg/kg/day of chlordiazepoxide either before (PRE, n = 8) or after (POST, n = 10) daily experimental sessions for 8 weeks. Cumulative dose-response curves for chlordiazepoxide were obtained before and during chronic chlordiazepoxide administration and during chronic saline administration. Cumulative dose-response curves for midazolam, FG 7142 (N-methyl-beta-carboline-3-carboxamide) flumazenil, pentobarbital, caffeine, morphine and d-amphetamine were determined before, during and 4.5 to 5 months after chronic chlordiazepoxide administration. Group PRE developed tolerance to chlordiazepoxide, whereas group POST did not develop tolerance. Although cross-tolerance developed to midazolam in both groups, it was greater in group PRE. Both groups showed comparable sensitization to FG 71 42 and neither group showed a significant change in sensitivity to any of the other drugs. Biochemical studies of gamma-aminobutyric acid (GABA)-related functioning in groups of rats that received chronic chlordiazepoxide administration either before (BIO-PRE, n = 6) or after (BIO-POST, n = 6) daily sessions found that GABA-stimulated Cl-36- uptake increased in both cortical and cerebellar preparations. However, GABA sensitivity in cerebellar tissue was significantly lower in group BIO-PRE compared with group BIO-POST. Thus, behavioral tolerance to chlordiazepoxide was associated with both pharmacological and biochemical effects, which suggests a relationship between behavioral tolerance to benzodiazepines and changes in the functional state of the GABA-benzodiazepine receptor complex. RP SANNERUD, CA (reprint author), NIDA,ADDICT RES CTR,BEHAV PHARMACOL & GENET SECT,PRECLIN PHARMACOL LAB,POB 5186,BALTIMORE,MD 21224, USA. NR 58 TC 17 Z9 17 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 1993 VL 267 IS 3 BP 1311 EP 1320 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MQ488 UT WOS:A1993MQ48800044 PM 8263795 ER PT J AU VAUPEL, DB LANGE, WR LONDON, ED AF VAUPEL, DB LANGE, WR LONDON, ED TI EFFECTS OF VERAPAMIL ON MORPHINE-INDUCED EUPHORIA, ANALGESIA AND RESPIRATORY DEPRESSION IN HUMANS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CALCIUM-ANTAGONISTS; PHYSIOLOGICAL-PARAMETERS; CHANNEL BLOCKERS; RATS; DEPENDENCE; TOLERANCE AB Organic calcium (Ca++) channel antagonists enhance opiate-induced analgesia and antagonize respiratory depression produced by morphine in rodents. Our preliminary data indicated that verapamil reduces the subjective effects of morphine in humans. We therefore assessed morphine-verapamil interactions in 12 experienced, male polydrug users with histories of heroin abuse by using a double-blind, cross-over study design. Treatments consisted of two drug infusions. Either verapamil, 2.5 or 10 mg, or saline was infused, 30 ml i.v. over 2 min; half way through this infusion either 1 0 mg of morphine or saline was infused, 3 ml i.v. over 1 0 sec, via a second catheter. Autonomic parameters, responsiveness to pain and subjective self-reports of mood and feeling state were measured over 4 hr. Analgesia was measured using a finger pressure test and hand immersion in ice water. Respiration was measured by using respiratory inductive plethysmography and transcutaneoUS CO2 levels. The Addiction Research Center Inventory (ARCI) was used to measure the subjective effects. Morphine had a liminal effect on pain threshold, but verapamil potentiated this effect to elevate pain threshold significantly. Verapamil did not affect the ability of morphine to increase pain endurance or to produce respiratory depression. Morphine produced positive affective responses, as demonstrated by elevated scores on the Morphine-Benzedrine Group subscale of the ARCI. Verapamil alone produced no effects on any ARCI subscales; however, 10 mg of verapamil significantly reduced morphine-elevated MBG scores over a 3-hr period. The results suggest the euphorigenic and analgesic effects of opioids may be differentiated by using Ca++ channel blockers. RP VAUPEL, DB (reprint author), NIDA,ADDICT RES CTR,MED AFFAIRS BRANCH,NEUROSCI BRANCH,NEUROIMAGING & DRUG ACT SECT,POB 5180,BALTIMORE,MD 21224, USA. NR 49 TC 20 Z9 20 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 1993 VL 267 IS 3 BP 1386 EP 1394 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MQ488 UT WOS:A1993MQ48800054 PM 8263800 ER PT J AU ANDREWS, AM MURPHY, DL AF ANDREWS, AM MURPHY, DL TI 2'-NH(2)-MPTP IN SWISS WEBSTER MICE - EVIDENCE FOR LONG-TERM (6-MONTH) DEPLETIONS IN CORTICAL AND HIPPOCAMPAL SEROTONIN AND NOREPINEPHRINE, DIFFERENTIAL PROTECTION BY SELECTIVE UPTAKE INHIBITORS OR CLORGYLINE AND FUNCTIONAL-CHANGES IN CENTRAL SEROTONIN NEUROTRANSMISSION SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CENTRAL CATECHOLAMINE NEURONS; DOPAMINERGIC NEUROTOXICITY; RAT-BRAIN; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MPTP; METHYLENEDIOXYMETHAMPHETAMINE MDMA; CHRONIC PARKINSONISM; 1-METHYL-4-PHENYL-1,2,5,6-TETRAHYDROPYRIDINE; MEPERIDINE; N-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; METABOLITE AB The i.p. administration of 1-methyl-4-(2'-aminophenyl)-1,2,3,6-tetrahydropyridine (2'-NH2-MPTP; 4 x 20 mg/kg) to Swiss Webster mice caused substantial decreases in cortical and hippocampal 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid and norepinephrine (NE) measured 1 week post-treatment. Compared with the authors' previously reported results in C57BL/6 mice, these effects were significantly greater in hippocampus (80-90% vs. 60%) and of a similar magnitude in frontal cortex (60-75%). A long-term study showed that cortical and hippocampal 5-HT, 5-hydroxyindoleacetic acid and NE were still decreased 40% to 50% 6 months after treatment. Regional brain dopamine was essentially unchanged during the 6-month period. Pretreatment with the 5-HT-selective uptake inhibitors, fluoxetine or paroxetine, or with the NE-selective uptake inhibitor, desipramine, prevented decreases in cortical and hippocampal 5-HT and NE, respectively, 3 weeks after 2'-NH2-MPTP (4 x 20 mg/kg). In addition, pretreatment with the monoamine oxidase type-A inhibitor, clorgyline, also prevented the more modest decreases in 5-HT and NE caused by 4 x 15 mg/kg 2'-NH2-MPTP. Selegiline, a monoamine oxidase-B inhibitor, did not provide similar protection. Lastly, 2'-NH2-MPTP administered 3 weeks earlier, abolished hypothermia caused by the serotonin agonist, m-chlorophenylpiperazine, which provided preliminary evidence for an associated functional change in the central serotonergic system. Together, these data suggest that 2'-NH2-MPTP is a novel agent capable of producing long-lasting depletions in forebrain 5-HT and NE but not dopamine in two different strains of mice by some mechanisms that resemble those of the parent dopamine-depleting neurotoxin, MPTP. C1 AMERICAN UNIV,DEPT CHEM,WASHINGTON,DC 20016. RP ANDREWS, AM (reprint author), NIMH,CLIN SCI LAB,BLDG 10,ROOM 3D41,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Andrews, Anne/B-4442-2011 OI Andrews, Anne/0000-0002-1961-4833 NR 39 TC 14 Z9 14 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 1993 VL 267 IS 3 BP 1432 EP 1439 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MQ488 UT WOS:A1993MQ48800061 PM 8263805 ER PT J AU STRECKFUS, CF BROWN, LJ SHIP, JA BRUNELLE, J AF STRECKFUS, CF BROWN, LJ SHIP, JA BRUNELLE, J TI STIMULATED PAROTID-GLAND FLOW-RATES IN HEALTHY, ELDERLY DENTULOUS AND EDENTULOUS INDIVIDUALS SO JOURNAL OF PROSTHETIC DENTISTRY LA English DT Article ID DIFFERENT AGE-GROUPS; SALIVA AB The use of dentures has been associated with increased stimulated parotid salivary dow rates (SPFR). A comparison of SPFRs was made between dentulous subjects having 20+ teeth (n = 190) and edentulous individuals (n = 67). Two different populations were selected, a white group from the Baltimore Longitudinal Study of Aging and an African-American group from the Washington Village Medical Center in Baltimore. Each group was healthy and unmedicated and had a mean age of 70.2 years. SPFR was determined with a Carlson-Crittenden cup and 2% citrate for stimulation. The edentulous subjects did not wear their dentures during salivary collection. The results indicated a significantly lower SPFR in dentate individuals compared with edentulous subjects (p < 0.01). Dentulous men also had a lower SPFR than edentulous men (p < 0.04). In addition, a pre- and postsurgical evaluation of 10 individuals who underwent full mouth tooth extractions revealed no differences in SPFR. These results suggest that edentulism per se does not have a deleterious effect on stimulated parotid salivary flow rates. C1 UNIV MICHIGAN,HOSP DENT,SCH DENT,NO CITY,MI. RP STRECKFUS, CF (reprint author), NIDR,EODPP,WESTWOOD BLDG,ROOM 718C,5333 WESTBARD AVE,BETHESDA,MD 20892, USA. NR 16 TC 7 Z9 7 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-3913 J9 J PROSTHET DENT JI J. Prosthet. Dent. PD DEC PY 1993 VL 70 IS 6 BP 496 EP 499 DI 10.1016/0022-3913(93)90261-L PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA MK132 UT WOS:A1993MK13200003 PM 8277436 ER PT J AU REINERT, DF ALLEN, JP FENZEL, LM ESTADT, BK AF REINERT, DF ALLEN, JP FENZEL, LM ESTADT, BK TI ALCOHOL RECOVERY IN SELF-HELP GROUPS - SURRENDER AND NARCISSISM SO JOURNAL OF RELIGION & HEALTH LA English DT Article ID PERSONALITY-INVENTORY; AFFILIATION AB This study was designed to determine if subjects participating more actively in Alcoholics Anonymous (AA) were higher on surrender and lower on pathological narcissism than those less involved in AA or participating in Rational Recovery. Male subject groups scored as predicted on surrender. As hypothesized, surrender also correlated negatively with pathological narcissism and was not associated with nonpathological narcissism. Results failed to support the predicted relationship between levels of participation in AA and pathological narcissism. A sex difference was found both on pathological narcissism and on surrender. Females scored lower on narcissism and higher on surrender than males. C1 NIAAA,ROCKVILLE,MD 20852. LOYOLA COLL,DEPT PASTORAL COUNSELING,COLUMBIA,MD. RP REINERT, DF (reprint author), CONCEPTION SEMINARY COLL,DEPT PSYCHOL,CONCEPTION,MO, USA. OI Reinert, Duane/0000-0002-5292-4382 NR 42 TC 3 Z9 3 U1 0 U2 1 PU HUMAN SCI PRESS INC PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 SN 0022-4197 J9 J RELIG HEALTH JI J. Relig. Health PD WIN PY 1993 VL 32 IS 4 BP 299 EP 308 DI 10.1007/BF00990956 PG 10 WC Public, Environmental & Occupational Health; Religion SC Public, Environmental & Occupational Health; Religion GA MH747 UT WOS:A1993MH74700007 PM 24271552 ER PT J AU KREY, G KELLER, H MAHFOUDI, A MEDIN, J OZATO, K DREYER, C WAHLI, W AF KREY, G KELLER, H MAHFOUDI, A MEDIN, J OZATO, K DREYER, C WAHLI, W TI XENOPUS PEROXISOME PROLIFERATOR ACTIVATED RECEPTORS - GENOMIC ORGANIZATION, RESPONSE ELEMENT RECOGNITION, HETERODIMER FORMATION WITH RETINOID-X RECEPTOR AND ACTIVATION BY FATTY-ACIDS SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT 11th International Symposium of the Journal of Steroid Biochemistry and Molecular Biology CY MAY 30-JUN 02, 1993 CL SEEFELD, AUSTRIA SP BIOMEDICA HANDELSGESELLSCH MBH, CIBA GEIGY LTD, FDN HORMONE RES, ICI, SCHERING BERLIN, SCHERING WIEN, SPORT & CONGRESS CTR, UNIV HOSP ID COA OXIDASE GENE; THYROID-HORMONE; OMEGA-HYDROXYLASE; BETA-OXIDATION; CLOFIBRIC ACID; SUPERFAMILY; INDUCTION; BINDING; MEMBER; FAMILY AB Peroxisome proliferator activated receptors are ligand activated transcription factors belonging to the nuclear hormone receptor superfamily. Three cDNAs encoding such receptors have been isolated from Xenopus laevis (xPPAR alpha, beta, and gamma). Furthermore, the gene coding for xPPAR beta has been cloned, thus being the first member of this subfamily whose genomic organization has been solved. Functionally, xPPAR alpha as well as its mouse and rat homologs are thought to play an important role in lipid metabolism due to their ability to activate transcription of a reporter gene through the promoter of the acyl-CoA oxidase (ACO) gene. ACO catalyzes the rate limiting step in the peroxisomal beta-oxidation of fatty acids. Activation is achieved by the binding of xPPAR alpha on a regulatory element (DR1) found in the promoter region of this gene, xPPAR beta and gamma are also able to recognize the same type of element and are, as PPAR alpha, able to form heterodimers with retinoid X receptor. All three xPPARs appear to be activated by synthetic peroxisome proliferators as well as by naturally occurring fatty acids, suggesting that a common mode of action exists for all the members of this subfamily of nuclear hormone receptors. C1 UNIV LAUSANNE,INST BIOL ANIM,CH-1015 LAUSANNE,SWITZERLAND. NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD 20892. MAX PLANCK INST ENTWICKLUNGSBIOL,W-7400 TUBINGEN,GERMANY. RI Wahli, Walter/B-1398-2009 OI Wahli, Walter/0000-0002-5966-9089 NR 31 TC 73 Z9 77 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD DEC PY 1993 VL 47 IS 1-6 BP 65 EP 73 DI 10.1016/0960-0760(93)90058-5 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA MP665 UT WOS:A1993MP66500009 PM 8274443 ER PT J AU TERRIN, ML WILLIAMS, DO KLEIMAN, NS WILLERSON, J MUELLER, HS DESVIGNENICKENS, P FORMAN, SA KNATTERUD, GL BRAUNWALD, E AF TERRIN, ML WILLIAMS, DO KLEIMAN, NS WILLERSON, J MUELLER, HS DESVIGNENICKENS, P FORMAN, SA KNATTERUD, GL BRAUNWALD, E TI 2-YEAR AND 3-YEAR RESULTS OF THE THROMBOLYSIS IN MYOCARDIAL-INFARCTION (TIMI) PHASE-II CLINICAL-TRIAL SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID THERAPY; SURVIVAL AB Objectives. This report describes the survival and reinfarction rates for 2- and 3-year follow up in the Thrombolysis in Myocardial Infarction (TIMI) Phase II clinical trial. Background. Patients enrolled in TIMI II were randomly assigned to an invasive (1,681 patients) or a conservative (1,658 patients) management strategy to follow receipt of intravenous recombinant tissue-type plasminogen activator for acute myocardial infarction. Methods. Eligibility required presentation within 4 h of onset of symptoms and at least 1-mV ST segment elevation in two contiguous electrocardiographic leads. The invasive strategy group underwent cardiac catheterization 18 to 48 h after study entry and, when appropriate, percutaneous transluminal coronary angioplasty or coronary artery bypass grafting. In the conservative strategy group these diagnostic and revascularization procedures were reserved for recurrent spontaneous ischemia or ischemia on low level exercise at the time of hospital discharge. Results. Complete 2-year follow-up data are available for 3,187 patients (95.4%). Cumulative life-table rates of death or reinfarction were 17.6% for the invasive strategy group and 17.9% for the conservative strategy group (p=NS) and mortality was 8.9% and 8.7% (p=NS), respectively. Complete data are available for 1,959 (90.1%) of the 2,174 patients enrolled for 3 years, Rates of death or reinfarction were 21.0% for the invasive strategy group and 20.0% for the conservative strategy group (p=NS), with mortality of 11.5% and 11.0% (p=NS), respectively. In this cohort, the mortality was 1.3% in the 2nd year and 1.7% in the 3rd year from study entry. Conclusions. TIMI II invasive and conservative strategies resulted is similar favorable outcomes after 2 and 3 years. Mortality and reinfarction rates in the two strategies were com parable. Deaths were infrequent in the 2nd and 3rd years from study entry. C1 BROWN UNIV,SCH MED,PROVIDENCE,RI 02912. BAYLOR COLL MED,HOUSTON,TX. UNIV TEXAS,DALLAS,TX 75230. ALBERT EINSTEIN COLL MED,MONTEFIORE MED CTR,NEW YORK,NY. NHLBI,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,BOSTON,MA. RP TERRIN, ML (reprint author), MARYLAND MED RES INST,600 WYNDHURST AVE,BALTIMORE,MD 21210, USA. NR 34 TC 61 Z9 61 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 DEC PY 1993 VL 22 IS 7 BP 1763 EP 1772 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA MQ366 UT WOS:A1993MQ36600002 PM 8245326 ER PT J AU ANTMAN, E DIMARCO, J DOMANSKI, MJ KNATTERUD, GL SCHEINMAN, M SINGER, D WALDO, A WOLF, PA WYSE, DG AF ANTMAN, E DIMARCO, J DOMANSKI, MJ KNATTERUD, GL SCHEINMAN, M SINGER, D WALDO, A WOLF, PA WYSE, DG TI ATRIAL-FIBRILLATION - CURRENT UNDERSTANDINGS AND RESEARCH IMPERATIVES SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID INTRAVENOUS PROCAINAMIDE INFUSION; INDEPENDENT RISK FACTOR; ATRIOVENTRICULAR JUNCTION; SINUS RHYTHM; CATHETER ABLATION; DRUG-THERAPY; FOLLOW-UP; STROKE; TACHYCARDIA; ARRHYTHMIAS AB Atrial fibrillation is the most common sustained cardiac arrhythmia encountered in clinical practice. Atrial fibrillation increases with age and is relatively common (> 5%) in patients > 69 years old. Despite this, our understanding of the underlying electrophysiologic mechanisms and the optimal management remains incomplete. This arrhythmia is seen most frequently in association with coronary disease or hypertension, but it is also frequently a consequence of rheumatic heart disease. The mechanism of atrial fibrillation requires further elucidation, but the most widely accepted hypothesis is a multiple reentrant wavelet mechanism. The treatment of atrial fibrillation is undertaken to reduce the risk of stroke or systemic embolus, to control palpitation or other symptoms or to improve exercise tolerance or treat pulmonary congestion. This report is a discussion of the epidemiology of atrial fibrillation and of the etiology, mechanism, management and future research directions in the study of this arrhythmia. C1 NHLBI, CLIN TRIALS BRANCH, BETHESDA, MD 20892 USA. BRIGHAM & WOMENS HOSP, DIV CARDIOL, BOSTON, MA 02115 USA. UNIV VIRGINIA, HLTH SCI CTR, DIV CARDIOL, CHARLOTTESVILLE, VA USA. BOSTON UNIV, BOSTON, MA 02215 USA. UNIV CALIF SAN FRANCISCO, MOFFITT HOSP, SAN FRANCISCO, CA 94143 USA. MASSACHUSETTS GEN HOSP, GEN INTERNAL MED UNIT, BOSTON, MA 02114 USA. UNIV HOSP CLEVELAND, DIV CARDIOL, CLEVELAND, OH 44106 USA. BOSTON UNIV, SCH MED, BOSTON, MA 02118 USA. UNIV CALGARY, MED CLIN, CALGARY, AB, CANADA. NR 57 TC 72 Z9 72 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC PY 1993 VL 22 IS 7 BP 1830 EP 1834 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA MQ366 UT WOS:A1993MQ36600012 ER PT J AU GOLDSTEIN, DS EISENHOFER, G DUNN, BB ARMANDO, I LENDERS, J GROSSMAN, E HOLMES, C KIRK, KL BACHARACH, S ADAMS, R HERSCOVITCH, P KOPIN, IJ AF GOLDSTEIN, DS EISENHOFER, G DUNN, BB ARMANDO, I LENDERS, J GROSSMAN, E HOLMES, C KIRK, KL BACHARACH, S ADAMS, R HERSCOVITCH, P KOPIN, IJ TI POSITRON EMISSION TOMOGRAPHIC IMAGING OF CARDIAC SYMPATHETIC INNERVATION USING 6-[F-18]FLUORODOPAMINE - INITIAL FINDINGS IN HUMANS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID NEURONAL UPTAKE; HUMAN-HEART; F-18 6-FLUORODOPAMINE; NERVOUS-SYSTEM; NOREPINEPHRINE; 6-FLUORO-L-DOPA; NEUROTRANSMITTERS; PLASMA; PET AB Objectives. This study evaluated the safety, efficacy and validity of 6-[F-18]fluorodopamine positron emission tomographic scanning of cardiac sympathetic innervation and function in humans. Methods. Positron emission tomographic (PET) scans, arterial blood and urine were obtained after a 3-min intravenous infusion of 6-[F-18]fluorodopamine (1 to 4 mCi, 188 to 809 mCi/mmol) in healthy volunteers, with or without pretreatment with oral desipramine to inhibit neuronal uptake of catecholamines. Results. 6-[F-18]Fluorodopamine PET scanning visualized the left ventricular myocardium. Blood pressure increased slightly and transiently. The estimated absorbed radiation dose to the main target organ, the wall of the urinary bladder, was 0.8 to 1.0 rad/mCi of injected 6-[F-18]fluoradopamine. By 24 h after the injection, the main 6F-compound in urine was 6F-vanillylmandelic acid, a metabolite of 6F-norepinephrine. Desipramine attenuated accumulation of myocardial 6-[F-18]fluorodopamine-derived radioactivity and plasma 6F-dihydroxyphenylacetic acid. Conclusions. 6-[F-18]Fluorodopamine produces negligible hemodynamic effects and acceptable radiation exposure at doses that visualize the left ventricular myocardium. Sympathetic nerves take up 6-[F-18]fluorodopamine, which is translocated from the axoplasm into storage vesicles, where is it beta-hydroxylated to the fluorinated analogue of the sympathetic neurotransmitter norepinephrine. Therefore, the basis for visualization of myocardium after 6-[F-18]fluorodopamine injection in humans is radiolabeling by 6-[F-18]fluorodopamine and 6-[F-18]fluoronorepinephrine of vesicles in sympathetic terminals. 6-[F-18]Fluorodopamine PET scanning provides a novel means for assessing sympathetic innervation and function noninvasively in the human heart. C1 NIH,CTR CLIN,DEPT POSITRON EMISS TOMOG,BETHESDA,MD 20892. NHLBI,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20892. NIDDKD,CHEM LAB,BETHESDA,MD. NIH,CTR CLIN,DEPT NUCL MED,BETHESDA,MD 20892. RP GOLDSTEIN, DS (reprint author), NINCDS,CLIN NEUROSCI BRANCH,BLDG 10,ROOM 5N262,BETHESDA,MD 20892, USA. NR 24 TC 60 Z9 60 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 DEC PY 1993 VL 22 IS 7 BP 1961 EP 1971 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA MQ366 UT WOS:A1993MQ36600033 PM 8245356 ER PT J AU VANHORN, LV STUMBO, P MOAGSTAHLBERG, A OBARZANEK, E HARTMULLER, VW FARRIS, RP KIMM, SYS FREDERICK, M SNETSELAAR, L LIU, K AF VANHORN, LV STUMBO, P MOAGSTAHLBERG, A OBARZANEK, E HARTMULLER, VW FARRIS, RP KIMM, SYS FREDERICK, M SNETSELAAR, L LIU, K TI THE DIETARY INTERVENTION STUDY IN CHILDREN (DISC) - DIETARY ASSESSMENT METHODS FOR 8-YEAR-OLDS TO 10-YEAR-OLDS SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; RECALL; NUTRITION; ACCURACY; VALIDITY; DESIGN AB Objectives The dietary assessment methods used in the Dietary Intervention Study in Children (DISC) are described and the rationale, validity, and/or general usefulness of each are discussed. Design DISC is the first multicenter, randomized, clinical trial to study the feasibility and long-term efficacy, safety, and acceptability of a fat-modified diet in 8- to 10-year-old prepubescent children with moderately elevated plasma low-density lipoprotein cholesterol (LDLC) levels. Final data collection for the original study (DISC T) occurred December 1, 1993; continued intervention and follow-up (DISC) will extend beyond 1997. Setting Six clinical centers across the country participate in DISC. Subjects Preadolescent boys and girls with fasting LDLC levels between the 80th and 98th age-specific and sex-specific percentiles established by the Lipid Research Clinics were eligible for the study. The feasibility phase included 140 children who were then enveloped into the full-scale trial. Baseline dietary data for 652 randomized children in the full-scale trial and 6-month results for the feasibility cohort are reported. Interventions Dietary assessment involved several elements: (a) determining eligibility based on consumption of more than 30% of energy from total fat., Co) monitoring adherence to and adequacy of the intervention diet, (c) evaluating acceptability of the diet in the intervention group, and (d) determining appropriate foods for the intervention diet. Methods are described for each purpose. Main outcome measures LDL-C differences between the two groups and differences in total and saturated fat intakes as calculated from three 24-hour recalls were the primary outcome measures. Six-month dietary differences in the feasibility group are reported. Statistical methods Baseline group means and 6-month differences in dietary intake are reported for the full-scale trial and feasibility study, respectively. Results Baseline mean intake from three dietary recalls for the intervention (n=328) and control (n=324) groups, respectively, were as follows: energy = 1,759 kcal and 1,728 kcal; total energy from fat = 33.3% and 34.0%; total energy from saturated fat = 12.5%, and 12.7%; and total dietary cholesterol = 209 mg and 195 mg. After 6 months of intervention, percentage of energy from total fat and saturated fat was reduced by 5.1% (P=.OO4) and 2.9% (P<.001), respectively, in this feasibility subset (n=73) of the intervention group. Essentially no change in these parameters occurred in the control group (n=67), which demonstrates a measurable difference in reporting between groups. Applications/conclusions Results illustrate the feasibility of implementing a variety of dietary assessment methods among preadolescent children without relying primarily on parental reports. C1 UNIV IOWA HOSP & CLIN,IOWA CITY,IA 52242. NHLBI,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,BALTIMORE,MD 21205. LOUISIANA STATE UNIV,SCH MED,DEPT PEDIAT,NEW ORLEANS,LA 70112. UNIV PITTSBURGH,DEPT CLIN EPIDEMIOL & PREVENT MED,PITTSBURGH,PA 15261. MARYLAND MED RES INST,DISC COORDINATING CTR,BALTIMORE,MD 21210. RP VANHORN, LV (reprint author), NORTHWESTERN UNIV,SCH MED,DEPT PREVENT MED,CHICAGO,IL 60611, USA. FU NHLBI NIH HHS [U01-HL-37947, U01-HL-37962, U01-HL-37975] NR 29 TC 77 Z9 79 U1 3 U2 6 PU AMER DIETETIC ASSN PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD DEC PY 1993 VL 93 IS 12 BP 1396 EP 1403 DI 10.1016/0002-8223(93)92241-O PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA MM037 UT WOS:A1993MM03700010 PM 8245373 ER PT J AU SHIMAKAWA, T WARRAM, JH HERRERAACENA, MG KROLEWSKI, AS AF SHIMAKAWA, T WARRAM, JH HERRERAACENA, MG KROLEWSKI, AS TI USUAL DIETARY-INTAKE AND HEMOGLOBIN A(1) LEVEL IN PATIENTS WITH INSULIN-DEPENDENT DIABETES SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; HIGH-CARBOHYDRATE DIET; HIGH-FIBER DIET; GLUCOSE CONTROL; BINDING; COMPLICATIONS; RETINOPATHY; ADIPOCYTES; MELLITUS; RISK AB Objective To explore epidemiologic evidence for the relation ship between dietary intake and glycemic control. Design/subjects We examined usual dietary intake, assessed by a food frequency questionnaire, from a random sample (n=136) of patients who had had insulin-dependent diabetes mellitus for 15 to 21 years. Results In men, absolute intakes of energy, carbohydrate, protein, fat, and dietary fiber were positively correlated with hemoglobin A(1) (HbA(1)) (P<.05); Spearman correlation coefficients (gamma(s)) were .28,.22,.28,.34, and.25, respectively. In women, the correlations were weaker and not significant; gamma(s) values were .18,.13,.17,.19, and .16, respectively. When these nutrients were expressed as a percentage of energy or as an amount per 1,000 kcal, only percentage of energy from fat showed a significant association with HbA(1)-but only in men (gamma(s)=.23 for ren and.02 for women). Adjustment for body weight, insulin dose, and physical activity using multiple regression analysis did not change the relationship between HbA(1) and intakes of energy and fat. Sucrose and alcohol intakes did not show any association with HbA,. Conclusions Among men with insulin-dependent diabetes mellitus, the major dietary correlates of poor glycemic control were high intake of energy and percentage of energy from fat. Further investigation is needed to confirm this relationship of energy, fat, and glycemic control. C1 JOSLIN DIABET CTR,DIV RES,EPIDEMIOL & GENET SECT,BOSTON,MA 02215. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,BOSTON,MA 02115. FU NIDDK NIH HHS [DK-41526] NR 33 TC 10 Z9 10 U1 0 U2 1 PU AMER DIETETIC ASSN PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD DEC PY 1993 VL 93 IS 12 BP 1409 EP & DI 10.1016/0002-8223(93)92243-Q PG 0 WC Nutrition & Dietetics SC Nutrition & Dietetics GA MM037 UT WOS:A1993MM03700012 PM 8245375 ER PT J AU LYTLE, LA NICHAMAN, MZ OBARZANEK, E GLOVSKY, E MONTGOMERY, D NICKLAS, T ZIVE, M FELDMAN, H AF LYTLE, LA NICHAMAN, MZ OBARZANEK, E GLOVSKY, E MONTGOMERY, D NICKLAS, T ZIVE, M FELDMAN, H TI VALIDATION OF 24-HOUR RECALLS ASSISTED BY FOOD RECORDS IN 3RD-GRADE CHILDREN SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID DIETARY RECALL; VALIDITY; RELIABILITY; POPULATION; NUTRITION; ACCURACY AB Objective The objective of the study nas to validate the use of 24-hour recalls assisted by food records as a dietary assessment tool tool use with third-grade children. Design Trained staff observed children during mealtime at school, and parents observed and recorded what children ate in their presence. The following day children participated in a 24-hour recall interview. Children's ability to recall what they consumed during a 24-hour period was compared with observational data collected during the same period. Setting All data were collected in elementary school settings at four sites involved in the Child and Adolescent Trial for Cardiovascular Health. Subjects The sample of 49 children was self-selected, based on parents' willingness to observe and record their child's food intake. Main outcome measures Recalled and observed data for energy and nutrient levels were compared using mean energy and nutrient analysis and quartile classification. In addition, recalled and observed foods were compared by meal type and estimation of portion size. Statistical analysis performed Paired t tests, Pearson and Spearman correlations, and classification analysis were used to compare recalled and observed data. Results Comparison of observed and recalled food intakes showed no significant differences in percentage of energy from total fat, saturated fat, monounsaturated fat, and polyunsaturated fat or in the amount of sodium consumed, although there were differences in energy intakes. Spearman rank order correlation; between recalled and observed nutrients ranged from .45 to .79. A 77.9% agreement was found across all meals in the food items children recalled and consumed compared with those adults actually observed them consuming. Conclusions We conclude that the 24-hour recall assisted by food records is a valid method for assessing the dietary intake of children as young as 8 years old for the purpose of group comparison. C1 UNIV TEXAS,HLTH SCI CTR,HOUSTON,TX 77225. UNIV TEXAS,CTR HLTH PROMOT,AUSTIN,TX 78712. NHLBI,BETHESDA,MD 20892. BOSTON UNIV,SCH MED,BOSTON,MA 02118. TULANE UNIV,SCH PUBL HLTH,NEW ORLEANS,LA 70112. UNIV CALIF SAN DIEGO,SCH CHILD & FAMILY HLTH STUDIES,DEPT PEDIAT,LA JOLLA,CA 92093. NEW ENGLAND RES INST,WATERTOWN,MA 02172. RP LYTLE, LA (reprint author), UNIV MINNESOTA,DIV EPIDEMIOL,MINNEAPOLIS,MN 55454, USA. FU NHLBI NIH HHS [U01 HL 39852, U01 HL 39870, U01 HL 39927] NR 24 TC 193 Z9 195 U1 1 U2 15 PU AMER DIETETIC ASSN PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD DEC PY 1993 VL 93 IS 12 BP 1431 EP 1436 DI 10.1016/0002-8223(93)92247-U PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA MM037 UT WOS:A1993MM03700015 PM 8245378 ER PT J AU SALIVE, ME BLAZER, DG AF SALIVE, ME BLAZER, DG TI DEPRESSION AND SMOKING CESSATION IN OLDER ADULTS - A LONGITUDINAL-STUDY SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID CIGARETTE-SMOKING; SYMPTOMS; CLONIDINE; MOOD AB Objective: To explore the relationship of smoking cessation and depression. Design: Cohort study with 3 years of follow-up. Setting: North Carolina community of the Established Populations for the Epidemiologic Studies of the Elderly. Participants: Stratified cluster sample of adults age 65 years and older, with an oversampling of African Americans. Main Measures: Depressive symptoms using a modified Center for Epidemiologic Studies Depression (CES-D) scale; smoking cessation using change in self-reported smoking. Results: Current smokers had the highest prevalence of clinically significant CES-D scores (11.2%), followed by never smokers (9.6%) and former smokers (7.1%). After 3 years, 128 (25%) of 511 baseline current smokers had quit. Among women with a clinically significant CES-D score, 55% quit smoking, compared with only 25% among those with a normal score (P < 0.05). Depressive symptoms were significantly associated with nearly fourfold increased odds of smoking cessation among women (relative odds [RO] 3.7, 95% confidence interval [CI] 1.2, 11.0; P < 0.05), but not among men (RO 0.6, 95% CI 0.2, 2.0, not significant), after adjusting for potential confounding. Conclusions: Depressive symptoms may directly increase the likelihood of smoking cessation among older women. When predicting smoking cessation, depression and gender should be considered in combination since to consider them separately may be misleading. This challenges prior reports that depressed smokers are less likely to quit smoking than non-depressed smokers. C1 DUKE UNIV,MED CTR,CTR STUDY AGING & HUMAN DEV,DURHAM,NC 27710. RP SALIVE, ME (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,7201 WISCONSIN AVE,GATEWAY BLDG,BETHESDA,MD 20892, USA. FU NIA NIH HHS [N01-AG-1-2102] NR 23 TC 33 Z9 33 U1 2 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 1993 VL 41 IS 12 BP 1313 EP 1316 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA MK559 UT WOS:A1993MK55900005 PM 8227913 ER PT J AU ALAVANJA, MCR BROWN, CC SWANSON, C BROWNSON, RC AF ALAVANJA, MCR BROWN, CC SWANSON, C BROWNSON, RC TI SATURATED FAT INTAKE AND LUNG-CANCER RISK AMONG NONSMOKING WOMEN IN MISSOURI SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID DIETARY VITAMIN-A; PROTEASE INHIBITOR; CIGARETTE-SMOKING; BETA-CAROTENE; HAWAII; MEN; CHOLESTEROL; VEGETABLES; CONSUMPTION; ASSOCIATION AB Background: Although the vast majority of lung cancer cases in women are caused by smoking, 9%-20% of cases occur in nonsmokers. Previous epidemiologic research on the relationship between lung cancer and diet has shown that fruit and vegetable consumption may confer a protective effect against lung cancer, while a diet rich in cholesterol and fat may increase risk. Purpose: The purpose of this case-control study was to examine the effects of a broad range of dietary factors on the risk of lung cancer in a population of nonsmoking white women 30-84 years of age. Methods: A telephone-administered questionnaire was used to determine and/or verify eligibility with regard to age, gender, race, and smoking status. In a second interview at the participant's home, a widely used food frequency questionnaire was filled out, and logistic regression was subsequently used to analyze the responses. We obtained dietary information on 429 case subjects who had a diagnosis of lung cancer reported to the Missouri Cancer Registry between June 1, 1986, and June 1, 1991, and 1021 control subjects. If a case subject had died or was too ill to be interviewed, next-of-kin familiar with the woman's diet were interviewed instead. Of the 429 women with lung cancer, 211 (49%) had lung adenocarcinoma. Results: A strongly increasing trend in lung cancer risk was observed with increased saturated fat consumption among these non-smoking women; the relative risk was more than six-fold greater for the highest quintile of consumption than for the lowest quintile. The effect of saturated fat was more pronounced for adenocarcinoma than for other cell types. Weekly servings of beans and peas were significantly-related to decreased lung cancer risk, while citrus fruit and juice showed a twofold increase in risk; this trend was also significant. Conclusion: By focusing on non-smoking women with lung cancer, including a large number with adenocarcinoma, we observed a clear association with saturated fat consumption that may have been masked in earlier studies of lung cancer involving a high percentage of smokers. C1 NCI,DIV CANC PREVENT & CONTROL,ROCKVILLE,MD 20852. MISSOURI DEPT HLTH,DIV CHRON DIS PREVENT & HLTH PROMOT,COLUMBIA,MO. RP ALAVANJA, MCR (reprint author), NCI,DIV CANC ETIOL,6130 EXECUT BLVD,RM 543,ROCKVILLE,MD 20852, USA. NR 53 TC 103 Z9 104 U1 2 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 DEC 1 PY 1993 VL 85 IS 23 BP 1906 EP 1916 DI 10.1093/jnci/85.23.1906 PG 11 WC Oncology SC Oncology GA MJ838 UT WOS:A1993MJ83800009 PM 8230280 ER PT J AU TRAVIS, LB CURTIS, RE GLIMELIUS, B HOLOWATY, E VANLEEUWEN, FE LYNCH, CF ADAMI, J GOSPODAROWICZ, M WACHOLDER, S INSKIP, P TUCKER, MA FRAUMENI, JF BOICE, JD AF TRAVIS, LB CURTIS, RE GLIMELIUS, B HOLOWATY, E VANLEEUWEN, FE LYNCH, CF ADAMI, J GOSPODAROWICZ, M WACHOLDER, S INSKIP, P TUCKER, MA FRAUMENI, JF BOICE, JD TI 2ND CANCERS AMONG LONG-TERM SURVIVORS OF NON-HODGKINS-LYMPHOMA SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ACUTE NONLYMPHOCYTIC LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; LUNG-CANCER; CYCLOPHOSPHAMIDE THERAPY; MALIGNANT-MELANOMA; MULTIPLE-MYELOMA; DISEASE; RISK; CARCINOMA; CHEMOTHERAPY AB Background: Patients with non-Hodgkin's lymphoma (NHL) are at increased risk for second cancers. Few studies, however, include long-term survivors, and none report risk for second cancer among NHL patients surviving 15 or more years. Purpose: Our aim was to examine the pattern of second cancers among long-term survivors of NHL. Methods: A cohort of 6171 patients diagnosed with NHL as a first primary cancer and who survived 2 or more years was identified within population-based tumor registries in Sweden, Ontario, and Iowa and within the affiliated tumor registry of The Netherlands Cancer Institute. Nearly 1000 NHL patients lived 15 or more years after diagnosis. Tumor registry files were searched for new invasive primary malignancies. Results: Second cancers were reported in 541 subjects (observed-to-expected ratio [O/E] = 1.37; 95% confidence interval = 1.26-1.49), with significant excesses seen for all solid tumors (O/E = 1.28), acute nonlymphocytic leukemia (O/E = 4.83), melanoma (O/E = 2.38), Hodgkin's disease (O/E = 12.0), and cancers of the lung (O/E = 1.36), brain (O/E = 2.33), kidney (O/E = 2.07), and bladder (O/E = 1.77). Among 15-year survivors, significantly increased risks persisted for all second cancers (O/E = 1.45), solid tumors (O/E = 1.37), bladder cancer (O/E = 3.24), and Hodgkin's disease (O/E = 25.0). The actuarial risk of developing a second cancer 3-20 years after diagnosis of NHL was 21%, compared with a population expected cumulative risk of 15%. Conclusions: Patients with NHL continue to be at significantly elevated risk of second primary cancer for up to two decades following diagnosis. The pattern of risk suggests the influence of treatment as well as factors associated with the underlying disease. Implications: Quantitative studies of second cancer following NHL are needed to clarify the role of antecedent therapy, shared risk factors, host susceptibility, and other etiologic and diagnostic influences. Despite the generally advanced age of patients with NHL, the persistently elevated risk of second cancers should alert clinicians to the importance of continued medical surveillance. C1 UNIV UPPSALA,DEPT ONCOL,S-75105 UPPSALA,SWEDEN. ONTARIO CANC TREATMENT & RES FDN,TORONTO,ON,CANADA. NETHERLANDS CANC INST,DEPT EPIDEMIOL,AMSTERDAM,NETHERLANDS. UNIV IOWA,STATE HLTH REGISTRY IOWA,IOWA CITY,IA 52242. UNIV UPPSALA,EPIDEMIOL UNIT,S-75105 UPPSALA,SWEDEN. UNIV TORONTO,DEPT RADIAT ONCOL,TORONTO M5S 1A1,ONTARIO,CANADA. RP TRAVIS, LB (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892, USA. RI Tucker, Margaret/B-4297-2015 NR 52 TC 151 Z9 156 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 DEC 1 PY 1993 VL 85 IS 23 BP 1932 EP 1937 DI 10.1093/jnci/85.23.1932 PG 6 WC Oncology SC Oncology GA MJ838 UT WOS:A1993MJ83800013 PM 8230284 ER PT J AU KALUZNY, A BRAWLEY, O GARSONANGERT, D SHAW, J GODLEY, P WARNECKE, R FORD, L AF KALUZNY, A BRAWLEY, O GARSONANGERT, D SHAW, J GODLEY, P WARNECKE, R FORD, L TI ASSURING ACCESS TO STATE-OF-THE-ART CARE FOR UNITED-STATES MINORITY POPULATIONS - THE 1ST 2 YEARS OF THE MINORITY-BASED COMMUNITY CLINICAL ONCOLOGY PROGRAM SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article AB Background: The Minority-Based Community Clinical Oncology Program (MBCCOP) was initiated in September 1990 to expand the National Cancer Institute's (NCI's) clinical trials network to minority populations. Institutions, organizations, and/or physician groups that had more than 50% of new cancer patients from minority groups were eligible to participate. There has been no previous evaluation of the MBCCOP. Purpose: This study was designed to describe the early implementation of the MBCCOP and identify the challenges that have emerged in developing a network aimed at increasing the participation of minority populations in clinical trials. Methods: Data were taken from primary and secondary sources, including site visits and patient log data, that described performance of 12 MBCCOP centers initially funded in September 1990. Accrual was measured by the number of credits earned per MBCCOP for patients enrolled in research protocols for cancer treatment or for prevention and control, which includes activities such as early detection, pain control, and rehabilitation. These accrual credits, assigned by the NCI, were based on the complexity of the protocol and the amount of resources expected to be required for accrual of patients by the MBCCOP. Results: Data for the first 2 years of the MBCCOP showed that 344 patients were accrued to trials of treatment protocols from June 1, 1990, to May 31, 1991, and this number increased to 470 during the second accrual year, June 1, 1991, to May 31, 1992. Similarly, accrual of patients to cancer prevention and control studies increased from 256 in 1990-1991 to 423 in 1991-1992. More than 70% of the MBCCOP patients entered in studies were from minority populations. The proportion of eligible MBCCOP patients entered into treatment protocols was identical with that experienced by the initial Community Clinical Oncology Program (CCOP). Results also demonstrated that MBCCOP centers operate in an environment characterized by socioeconomic decline and limited resources, both having substantial effects on the implementation of clinical trials among minorities. While minority patients are willing to participate in clinical trials, there are profound barriers involving language, logistics, and the appropriateness of available protocols. Participating physicians, nurses, and support personnel report a high level of agreement with program goals and have developed unique approaches to meeting the challenges faced in the implementation of this program. Conclusions: The MBCCOPs have demonstrated their ability to participate in clinical trials. Evaluation reveals, however, that they are emerging organizations influenced by factors endemic to the community they serve and their own structure. The MBCCOPs are confronting substantial challenges, yet they provide an important link to the overall NCI clinical trials network. C1 NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. UNIV N CAROLINA,DEPT MED,CHAPEL HILL,NC 27514. UNIV ILLINOIS,SURVEY RES LABS,CHICAGO,IL 60680. RP KALUZNY, A (reprint author), UNIV N CAROLINA,CECIL G SHEPS CTR HLTH SERV,LINEBERGER COMPREHENS CANC CTR,CB 7590,CHAPEL HILL,NC 27599, USA. NR 7 TC 51 Z9 51 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 1 PY 1993 VL 85 IS 23 BP 1945 EP 1950 DI 10.1093/jnci/85.23.1945 PG 6 WC Oncology SC Oncology GA MJ838 UT WOS:A1993MJ83800015 PM 8230286 ER PT J AU SEPULVEDA, W BERRY, SM ROMERO, R KING, ME JOHNSON, MP COTTON, DB AF SEPULVEDA, W BERRY, SM ROMERO, R KING, ME JOHNSON, MP COTTON, DB TI PRENATAL-DIAGNOSIS OF CONGENITAL MEGALOURETHRA SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Note ID FETAL C1 WAYNE STATE UNIV,HUTZEL HOSP,SCH MED,DEPT OBSTET & GYNECOL,DETROIT,MI 48201. NICHHD,PERINATOL BRANCH,BETHESDA,MD. NR 24 TC 13 Z9 13 U1 0 U2 1 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD DEC PY 1993 VL 12 IS 12 BP 761 EP 766 PG 6 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA MK150 UT WOS:A1993MK15000012 PM 8301718 ER PT J AU KIRNBAUER, R TAUB, J GREENSTONE, H RODEN, R DURST, M GISSMANN, L LOWY, DR SCHILLER, JT AF KIRNBAUER, R TAUB, J GREENSTONE, H RODEN, R DURST, M GISSMANN, L LOWY, DR SCHILLER, JT TI EFFICIENT SELF-ASSEMBLY OF HUMAN PAPILLOMAVIRUS TYPE-16 L1 AND L1-L2 INTO VIRUS-LIKE PARTICLES SO JOURNAL OF VIROLOGY LA English DT Article ID OPEN READING FRAME; MOLECULAR-CLONING; CELL-LINE; EXPRESSION; INFECTION; PROTEINS; NEUTRALIZATION; IMMUNIZATION; VACCINATION; DNA AB The L1 genes of two human papillomavirus type 16 (HPV16) isolates derived from condylomata acuminata were used to express the Ll major capsid protein in insect cells via recombinant baculoviruses. Both L1 major capsid proteins self-assembled into virus-like particles (VLP) with high efficiency and could be purified in preparative amounts on density gradients. The yield of VLP was 3 orders of magnitude higher than what has been obtained previously, using L1 derived from the prototype HPV16. DNA sequence comparison identified a single nonconserved amino acid change to be responsible for the inefficient self-assembly of the prototype L1. VLP were also obtained by expressing L1 of HPV6, HPV11, and cottontail rabbit papillomavirus, indicating that L1 from a variety of papillomaviruses has the intrinsic capacity to self-assemble into VLP. Coexpression of HPV16 L1 plus L2 by using a baculovirus double-expression vector also resulted in efficient self-assembly of VLP, and the average particle yield increased about fourfold in comparison to when L1 only was expressed. Coimmunoprecipitation of L1 and L2 and cosedimentation of the two proteins in a sucrose gradient demonstrated that L2 was incorporated into the particles. The ability to generate preparative amounts of HPV16 L1 and L1-L2 VLP may have implications for the development of a serological assay to detect anti-HPV16 virion immune responses to conformational epitopes and for immunoprophylaxis against HPV16 infection. C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. DEUTSCH KREBSFORSCHUNGSZENTRUM,W-6900 HEIDELBERG,GERMANY. RI Gissmann, Lutz/H-4688-2011 NR 23 TC 396 Z9 415 U1 0 U2 25 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 DEC PY 1993 VL 67 IS 12 BP 6929 EP 6936 PG 8 WC Virology SC Virology GA MG307 UT WOS:A1993MG30700003 PM 8230414 ER PT J AU HUANG, LM JEANG, KT AF HUANG, LM JEANG, KT TI INCREASED SPACING BETWEEN SP1 AND TATAA RENDERS HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REPLICATION-DEFECTIVE - IMPLICATION FOR TAT FUNCTION SO JOURNAL OF VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; RNA-BINDING PROTEIN; NF-KAPPA-B; HIV-1 TAT; TRANSCRIPTIONAL ACTIVATION; MAMMALIAN-CELLS; NASCENT RNA; PROMOTER; INFECTIVITY; SEQUENCE AB Expression of the human immunodeficiency virus type 1 (HIV-1) is strongly activated by Tat. The proper action of Tat requires three elements: TATAA, TAR, and upstream motifs in the HIV-1 long terminal repeat. We show here that the correct spatial arrangement among Tat, Sp1, and TATAA crucially influences HIV expression. Under conditions in which basal promoter activity is unperturbed, distancing Spl from TATAA markedly affected Tat trans activation. An increase in the Sp1-TATAA distance from 18 to 101 nucleotides (depending on the inserted sequence) rendered HIV-1 either partially or wholly replication defective. This critical dependence on spacing suggests that Tat-, Sp1-, and TATAA-binding factors must correctly contact each other for optimal expression and replication of HIV-1. C1 NIAID,MOLEC MICROBIOL LAB,BLDG 4,ROOM 306,BETHESDA,MD 20892. RI Jeang, Kuan-Teh/A-2424-2008; OI Huang, Li-Min/0000-0002-9291-260X NR 48 TC 42 Z9 42 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1993 VL 67 IS 12 BP 6937 EP 6944 PG 8 WC Virology SC Virology GA MG307 UT WOS:A1993MG30700004 PM 8230415 ER PT J AU KANNO, H WOLFINBARGER, JB BLOOM, ME AF KANNO, H WOLFINBARGER, JB BLOOM, ME TI ALEUTIAN MINK DISEASE PARVOVIRUS INFECTION OF MINK MACROPHAGES AND HUMAN MACROPHAGE CELL-LINE U937 - DEMONSTRATION OF ANTIBODY-DEPENDENT ENHANCEMENT OF INFECTION SO JOURNAL OF VIROLOGY LA English DT Article ID DEHYDROGENASE-ELEVATING VIRUS; ADULT MINK; INTERSTITIAL PNEUMONIA; NEUTRALIZING ANTIBODY; VIRAL REPLICATION; FC RECEPTOR; PROTEIN; IDENTIFICATION; HYBRIDIZATION; MECHANISM AB Aleutian mink disease parvovirus (ADV) infects macrophages in adult mink. The virulent ADV-Utah I strain, but not the cell culture-adapted ADV-G strain, infects mink peritoneal macrophage cultures and the human macrophage cell line U937 in vitro. However, preincubation of ADV-G with ADV-infected mink serum enhanced its infectivity for U937 cells. The enhancing activity was present in the protein A-binding immunoglobulin G fraction in the serum, but F(ab')2 fragments failed to enhance the infection. On the other hand, the same sera inhibited ADV-G infection of Crandell feline kidney (CRFK) cells. Although U937 cells were not fully permissive for antibody-enhanced ADV-G infection, ADV mRNA expression, genome amplification, and protein expression were identical to those found previously for ADV-Utah I infection of U937 cells. Preincubation of ADV-Utah I with soluble protein A partly inhibited the infection of U937 cells but did not affect infection of CRFK cells. In mink peritoneal macrophages, preincubation with the infected mink serum did not make ADV-G infectious. However, the infectivity for mink macrophages of antibody-free ADV-Utah I prepared from the lungs of infected newborn mink kits was enhanced by ADV-infected mink serum. Moreover, protein A partly blocked ADV-Utah I infection of mink macrophage cultures. These results suggested that ADV-Utah I enters mink macrophages and U937 cells via an Fc receptor-mediated mechanism. This mechanism, antibody-dependent enhancement, may also contribute to ADV infection in vivo. Furthermore, since ADV infection in mink is characterized by overproduction of anti-ADV immunoglobulins, antibody-dependent enhancement may play a critical role in the establishment of persistent infection with ADV in vivo. C1 NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840. NR 46 TC 33 Z9 33 U1 3 U2 8 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 DEC PY 1993 VL 67 IS 12 BP 7017 EP 7024 PG 8 WC Virology SC Virology GA MG307 UT WOS:A1993MG30700015 PM 8230426 ER PT J AU ROVNAK, J BOYD, AL CASEY, JW GONDA, MA JENSEN, WA COCKERELL, GL AF ROVNAK, J BOYD, AL CASEY, JW GONDA, MA JENSEN, WA COCKERELL, GL TI PATHOGENICITY OF MOLECULARLY CLONED BOVINE LEUKEMIA-VIRUS SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; NUCLEOTIDE-SEQUENCE; PERSISTENT LYMPHOCYTOSIS; GENOMIC INTEGRATION; INFECTED CATTLE; BLV INFECTION; ENV GENE; B-CELLS; SHEEP; EXPRESSION AB To delineate the mechanisms of bovine leukemia virus (BLV) pathogenesis, four full-length BLV clones, 1, 8, 9, and 13, derived from the transformed cell line FLK-BLV and a clone construct, pBLV913, were introduced into bovine spleen cells by microinjection. Microinjected cells exhibited cytopathic effects and produced BLV p24 and gp51 antigens and infectious virus. The construct, pBLV913, was selected for infection of two sheep by inoculation of microinjected cells. After 15 months, peripheral blood mononuclear cells from these sheep served as inocula for the transfer of infection to four additional sheep. All six infected sheep seroconverted to BLV and had detectable BLV DNA in peripheral blood mononuclear cells after amplification by polymerase chain reaction. Four of the six sheep developed altered B/T-lymphocyte ratios between 33 and 53 months postinfection. One sheep died of unrelated causes, and one remained hematologically normal. Two of the affected sheep developed B lymphocytosis comparable to that observed in animals inoculated with peripheral blood mononuclear cells from BLV-infected cattle. This expanded B-lymphocyte population was characterized by elevated expression of B-cell surface markers, spontaneous blastogenesis, virus expression in vitro, and increased, polyclonally integrated provirus. One of these two sheep developed lymphocytic leukemia-lymphoma at 57 months postinfection. Leukemic cells had the same phenotype and harbored a single, monoclonally integrated provirus but produced no virus after in vitro cultivation. The range in clinical response to in vivo infection with cloned BLV suggests an important role for host immune response in the progression of virus replication and pathogenesis. C1 HOOD COLL,DEPT BIOL,FREDERICK,MD 21701. NEW YORK STATE COLL VET MED,DEPT MICROBIOL & IMMUNOL,ITHACA,NY 14853. NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,CELL & MOLEC STRUCT LAB,FREDERICK,MD 21702. COLORADO STATE UNIV,DEPT PATHOL,FT COLLINS,CO 80523. FU NCI NIH HHS [CA-43728]; NIAID NIH HHS [AI/CA-00924] NR 60 TC 20 Z9 20 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 DEC PY 1993 VL 67 IS 12 BP 7096 EP 7105 PG 10 WC Virology SC Virology GA MG307 UT WOS:A1993MG30700024 PM 8230433 ER PT J AU SUBBARAO, EK KAWAOKA, Y MURPHY, BR AF SUBBARAO, EK KAWAOKA, Y MURPHY, BR TI RESCUE OF AN INFLUENZA-A VIRUS WILD-TYPE PB2 GENE AND A MUTANT DERIVATIVE BEARING A SITE-SPECIFIC TEMPERATURE-SENSITIVE AND ATTENUATING MUTATION SO JOURNAL OF VIROLOGY LA English DT Article ID REASSORTANT VIRUSES; SQUIRREL-MONKEYS; SEQUENCE CHANGES; POLYMERASE; NEURAMINIDASE; H2N2; RNA AB Live attenuated influenza A virus vaccines are currently produced by the transfer of attenuating genes from a donor virus to new epidemic variants of influenza A virus, with the selection of reassortant viruses that possess the protective antigens (i.e., the two surface glycoproteins) of the epidemic virus and the attenuating genes from the donor virus. The previously studied attenuated donor viruses were produced by conventional methods such as passage of virus at low temperature or chemical mutagenesis. The present paper describes a new strategy for the generation of a donor virus bearing an attenuating, non-surface-glycoprotein gene. This strategy involves the introduction of attenuating mutations into the cDNA copy of the PB2 polymerase gene by site-directed mutagenesis, transfection of in vitro RNA transcripts of PB2 cDNA, and recovery of the transfected PB2 gene into an infectious virus. An avian-human influenza A virus PB2 single-gene reassortant virus (with an avian influenza A virus PB2 gene) that replicates efficiently in avian tissue but poorly in mammalian cells was used as a helper virus to rescue a transfected synthetic RNA derived from a human influenza A virus PB2 gene. The desired human influenza A virus mutant PB2 transfectant was favored in this situation because the avian influenza A virus PB2 gene restricts viral replication in mammalian cells in culture, the system used for rescue, thereby providing strong selection for the virus bearing the human influenza A virus PB2 gene. We validated the feasibility of this approach by rescuing the PB2 gene of the wild-type influenza A/Ann Arbor/6/60 virus and a mutant derivative that had a single amino acid substitution introduced at position 265 by site-directed mutagenesis. Previously, this amino acid substitution had been shown to specify both a temperature-sensitive (ts) and an attenuation (att) phenotype. The rescued mutant 265 PB2 transfectant virus exhibited the ts and att phenotypes, which confirms that these phenotypes were specified by this single amino acid substitution. The transfectant virus was immunogenic and protected hamsters from subsequent challenge with wild-type virus. The cDNA copy of this influenza A/Ann Arbor/6/60 virus mutant 265 PB2 gene will be used as a substrate for the introduction of additional attenuating mutations by site-directed mutagenesis. C1 ST JUDE CHILDRENS RES HOSP, DEPT VIROL & MOLEC BIOL, MEMPHIS, TN 38101 USA. RP SUBBARAO, EK (reprint author), NIAID, INFECT DIS LAB, RESP VIRUSES SECT, BETHESDA, MD 20892 USA. FU NCI NIH HHS [CA-21765]; NIAID NIH HHS [AI-29599] NR 19 TC 53 Z9 60 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1993 VL 67 IS 12 BP 7223 EP 7228 PG 6 WC Virology SC Virology GA MG307 UT WOS:A1993MG30700037 PM 8230444 ER PT J AU GITLIN, SD DITTMER, J SHIN, RC BRADY, JN AF GITLIN, SD DITTMER, J SHIN, RC BRADY, JN TI TRANSCRIPTIONAL ACTIVATION OF THE HUMAN T-LYMPHOTROPIC VIRUS TYPE-I LONG TERMINAL REPEAT BY FUNCTIONAL INTERACTION OF TAX(1) AND ETS1 SO JOURNAL OF VIROLOGY LA English DT Article ID CELL LEUKEMIA-VIRUS; TROPICAL SPASTIC PARAPARESIS; ENCODING NUCLEAR PROTEINS; COLONY-STIMULATING FACTOR; RECEPTOR GENE-EXPRESSION; HTLV-I; INTERLEUKIN-2 RECEPTOR; DNA-BINDING; C-ETS; PROTO-ONCOGENE AB Transcription regulation of the oncogenic retrovirus human T-lymphotropic virus type I (HTLV-I) involves the composite activity of both viral and cellular transcription factors. The HTLV-I transforming protein, Tax1, modulates the activity of several cellular transcription factors, upregulating the level of viral gene expression. In addition, cellular transcription factors, such as Ets1, independently bind to the viral long terminal repeat in a sequence-specific manner and activate transcription. It was of interest to analyze the possible interaction of Tax1 and Ets1 in viral gene regulation. We now report that Tax1 and Ets1 increase expression from the HTLV-1 promoter in a cooperative manner. The level of expression was increased 5- to 10-fold above the combined individual effect of Tax1 and Ets1. S1 nuclease analysis demonstrated that the cooperative effect was due to an increase in the levels of steady-state RNA. The functional interaction between Tax1 and Ets1 required the presence of the Tax1-responsive 21-bp repeat element TRE-1 and the Ets1-responsive element ERR-1. These results suggested the possible interaction of Ets1 with transcriptional regulatory proteins that bind to the 21-bp repeats. This interaction is demonstrated by decreased electrophoretic mobility of specific 21-bp repeat gel shift complexes in the presence of Ets1. Furthermore, interaction of Ets1 with the 21-bp repeat-binding proteins enhances the relative efficiency of binding to the DNA. This cooperative interaction between Ets1 and proteins which bind to the Tax1-responsive 21-bp repeats suggests a possible role for Ets1 in the regulation of viral gene expression. C1 NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. HOWARD HUGHES MED INST,BETHESDA,MD 20814. RI Dittmer, Juergen/G-1160-2011 NR 82 TC 29 Z9 29 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 DEC PY 1993 VL 67 IS 12 BP 7307 EP 7316 PG 10 WC Virology SC Virology GA MG307 UT WOS:A1993MG30700047 PM 8230454 ER PT J AU NUSSBAUM, O ROOP, A ANDERSON, WF AF NUSSBAUM, O ROOP, A ANDERSON, WF TI SEQUENCES DETERMINING THE PH-DEPENDENCE OF VIRAL ENTRY ARE DISTINCT FROM THE HOST RANGE-DETERMINING REGION OF THE MURINE ECOTROPIC AND AMPHOTROPIC RETROVIRUS ENVELOPE PROTEINS SO JOURNAL OF VIROLOGY LA English DT Article ID CELLS; INFLUENZA; VIRUSES; FUSION AB The entry of ecotropic and amphotropic murine leukemia retroviruses (MuLV) into cells was investigated by using viral vector particles carrying chimeric amphotropic-ecotropic envelope glycoproteins on their surface. Chimeras were made by joining, at or near the polyproline hinge, the N-terminal portion of the amphotropic (4070A) gp70 onto the C-terminal portion of the ecotropic (Moloney) gp70 and p15E (constructs AE2 and AE4) or vice versa (AE12). Transduction efficiency of the constructs was tested on target cells that either have only ecotropic receptors (CHO-2 and CHO-11 cells), only amphotropic receptors (mink lung fibroblasts and Cos 1 cells), or both types of receptors (NIH 3T3 cells). The assay made use of the fact that the mechanism for viral entry of ecotropic viruses is pH dependent while that of amphotropic viruses is pH independent. Treatment of target cells with NH4Cl, which prevents the reduction of pH within endosomes, reduced the titers of viral particles bearing the C-terminal moiety from the ecotropic envelope but did not reduce the titers of particles which had a C-terminal moiety from the amphotropic envelope. In addition, in contrast to other low-pH-dependent enveloped viruses, brief acid treatment did not allow surface-bound viruses to bypass the NH4Cl block. The results indicate that the pH dependence of viral entry is a property of the sequences C terminal to the polyproline hinge. RP NUSSBAUM, O (reprint author), NHLBI,MOLEC HEMATOL BRANCH,BLDG 10,ROOM 7D-18,BETHESDA,MD 20892, USA. NR 16 TC 46 Z9 46 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1993 VL 67 IS 12 BP 7402 EP 7405 PG 4 WC Virology SC Virology GA MG307 UT WOS:A1993MG30700057 PM 8230461 ER PT J AU WATKINS, BA REITZ, MS WILSON, CA ALDRICH, K DAVIS, AE ROBERTGUROFF, M AF WATKINS, BA REITZ, MS WILSON, CA ALDRICH, K DAVIS, AE ROBERTGUROFF, M TI IMMUNE ESCAPE BY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 FROM NEUTRALIZING ANTIBODIES - EVIDENCE FOR MULTIPLE PATHWAYS SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; HTLV-III; SYNTHETIC PEPTIDES; ENVELOPE GLYCOPROTEIN; DEFICIENCY SYNDROME; GENOMIC DIVERSITY; HIV-1 INFECTION; POINT MUTATION; VIRAL ENVELOPE; GP120 AB Sera from many HIV-1-infected individuals contain broadly reactive, specific neutralizing antibodies. Despite their broad reactivity, variant viruses, resistant to neutralization, can be selected in vitro in the presence of such antisera. We have previously shown that neutralization resistance of an escape mutant with an amino acid substitution in the transmembrane protein (A582T) occurs because of alteration or a conformational epitope that is recognized by neutralizing antibodies directed against the CD4 binding site. In this report we demonstrate that immune escape via a single-amino-acid substitution (A281V) within a conserved region of the envelope glycoprotein gp120 confers neutralization resistance against a broadly reactive neutralizing antiserum from a seropositive individual. We show this alteration affects V3 and additional regions unrelated to V3 or the CD4 binding site. Together with previous studies on escape mutants selected in vitro, our findings suggest that immune-selective pressure can arise by multiple pathways. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NR 51 TC 52 Z9 52 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 DEC PY 1993 VL 67 IS 12 BP 7493 EP 7500 PG 8 WC Virology SC Virology GA MG307 UT WOS:A1993MG30700068 PM 7693973 ER PT J AU MEIER, JL STRAUS, SE AF MEIER, JL STRAUS, SE TI VARICELLA-ZOSTER VIRUS-DNA POLYMERASE AND MAJOR DNA-BINDING PROTEIN GENES HAVE OVERLAPPING DIVERGENT PROMOTERS SO JOURNAL OF VIROLOGY LA English DT Article ID EPSTEIN-BARR VIRUS; EXPRESSION; TRANSCRIPTION; SEQUENCE; CELLS; LATENCY; REGION; YEAST AB A detailed analysis of the transcriptionally divergent promoters of varicella-zoster virus (VZV) open reading frames (ORFs) 28 and 29, encoding the DNA polymerase and major DNA-binding proteins, respectively, was performed. We found that the 221-bp ORF 28-29 intergenic domain contains overlapping divergent promoters; these promoters have TATA boxes and cap sites arranged closely back-to-back, have highly concordant patterns of responsiveness to transactivation by VZV ORFs 4 and/or 62, and could not be separated without abolishing the effects that VZV trans activators imparted to them. Mutation of the ORF 28 TATA box rendered this promoter unresponsive to ORF 62 and the combination of ORFs 4 and 62 without altering ORF 29 promoter activity. Mutations of all potential ORF 29 TATA boxes collectively failed to abolish this promoter's responsiveness to either ORF 4 or ORF 62, suggesting a mechanism of gene regulation for ORF 29 tbat differs from that of ORF 28. These findings are concordant with the observation that both genes are expressed in productive infection, but only ORF 29 expression has been identified in latency. C1 NIAID,CLIN INVEST LAB,MED VIROL SECT,BETHESDA,MD 20892. NR 29 TC 23 Z9 24 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 DEC PY 1993 VL 67 IS 12 BP 7573 EP 7581 PG 9 WC Virology SC Virology GA MG307 UT WOS:A1993MG30700077 PM 8230477 ER PT J AU PARDI, D KAPLAN, JE COLIGAN, JE FOLKS, TM LAL, RB AF PARDI, D KAPLAN, JE COLIGAN, JE FOLKS, TM LAL, RB TI IDENTIFICATION AND CHARACTERIZATION OF AN EXTENDED TAX PROTEIN IN HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-II SUBTYPE-B ISOLATES SO JOURNAL OF VIROLOGY LA English DT Note ID TROPICAL SPASTIC PARAPARESIS; INTRAVENOUS-DRUG-USERS; HTLV-II; LEUKEMIA-VIRUS; INFECTION; DISEASE; ABUSERS; RETROVIRUS; PREVALENCE; EPITOPES AB The tar gene sequence of human T-cell lymphotropic virus type II isolate G12 (HTLV-II(G12)) was found to encode an extended Tax protein when compared with that of HTLV-II(MoT). In vitro transcription-translation of the HTLV-II(G12) tar gene produced a 40-kDa Tax protein that specifically reacted with serum specimens from HTLV-II-infected individuals. Limited sequence analysis demonstrated that isolates with an extended Tax protein were all HTLV-II subtype b (HTLV-IIb). Therefore, the extended Tax protein appears to be a unique characteristic of most HTLV-IIb isolates and may be useful in designing immunoassays to distinguish between HTLV-IIa and HTLV-IIb. C1 NIAID,BIOL RESOURCES BRANCH,BETHESDA,MD 20894. RP PARDI, D (reprint author), CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,RETROVIRUS DIS BRANCH,ATLANTA,GA 30333, USA. NR 33 TC 24 Z9 24 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 DEC PY 1993 VL 67 IS 12 BP 7663 EP 7667 PG 5 WC Virology SC Virology GA MG307 UT WOS:A1993MG30700090 PM 8230487 ER PT J AU FRANCHINI, G MULLOY, JC KORALNIK, IJ LOMONICO, A SPARKOWSKI, JJ ANDRESSON, T GOLDSTEIN, DJ SCHLEGEL, R AF FRANCHINI, G MULLOY, JC KORALNIK, IJ LOMONICO, A SPARKOWSKI, JJ ANDRESSON, T GOLDSTEIN, DJ SCHLEGEL, R TI THE HUMAN T-CELL LEUKEMIA LYMPHOTROPIC VIRUS TYPE-I P12(I) PROTEIN COOPERATES WITH THE E5 ONCOPROTEIN OF BOVINE PAPILLOMAVIRUS IN CELL-TRANSFORMATION AND BINDS THE 16-KILODALTON SUBUNIT OF THE VACUOLAR H+-ATPASE SO JOURNAL OF VIROLOGY LA English DT Note ID GROWTH-FACTOR RECEPTOR; TROPICAL SPASTIC PARAPARESIS; HTLV-I; GENE-EXPRESSION; LYMPHOMA VIRUS; ANTIBODIES; ACTIVATION; LYMPHOCYTES; RETROVIRUS; COMPONENT AB The human T-cell leukemia/lymphotropic virus type I (HTLV-1) induces T-cell leukemia and transforms human T cells in vitro. A recently identified protein with a molecular weight of 12,000 (12K) (p12I), encoded by single- and double-spliced mRNAs transcribed from the 3' end of the HTLV-I genome, has been shown to localize in the perinuclear compartment and in the cellular endomembranes. The p12I protein exhibits significant amino acid sequence similarity to the E5 oncoprotein of bovine papillomavirus type 1 (BPV-1). Both proteins are very hydrophobic, contain a glutamine residue in the middle of a potential transmembrane region(s), and are localized in similar cellular compartments. Because of these observations, we investigated whether the p12I resemblance to E5 correlated with a similarity in their biological behavior. We expressed the p12I protein to evaluate its ability to functionally cooperate with the BPV-1 E5 oncoprotein and to bind to a cellular target of the E5 protein, the 16K component of the vacuolar H+ ATPase. Cotransfection of the mouse C127 cell line with the p12I and E5 cDNAs showed that although p12I alone could not induce focus formation, it strongly potentiated the transforming activity of E5. In addition, the p12I protein bound to the 16K protein as efficiently as the E5 protein. These findings might provide new insight for potential mechanisms of HTLV-1 transformation and suggest that p12I and E5 represent an example of convergent evolution between RNA and DNA viruses. C1 GEORGETOWN UNIV,SCH MED,DEPT PATHOL,WASHINGTON,DC 20057. RP FRANCHINI, G (reprint author), NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 39 TC 114 Z9 114 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 DEC PY 1993 VL 67 IS 12 BP 7701 EP 7704 PG 4 WC Virology SC Virology GA MG307 UT WOS:A1993MG30700098 PM 8230493 ER PT J AU GAMBARO, G VENTURINI, AP BRUNELLO, A VINCENTI, M FRIES, W NOONAN, D BERTAGLIA, G MARCHI, E BAGGIO, B AF GAMBARO, G VENTURINI, AP BRUNELLO, A VINCENTI, M FRIES, W NOONAN, D BERTAGLIA, G MARCHI, E BAGGIO, B TI MECHANISMS OF THE PREVENTIVE ACTIVITY OF GLYCOSAMINOGLYCANS ON EXPERIMENTAL DIABETIC NEPHROPATHY SO KIDNEY INTERNATIONAL LA English DT Meeting Abstract C1 UNIV PADUA,INST INTERNAL MED,PADUA,ITALY. NATL CANC INST,GENOA,ITALY. ALFA WASSERMANN SPA,DIV RES,BOLOGNA,ITALY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 1993 VL 44 IS 6 BP 1395 EP 1395 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA MF717 UT WOS:A1993MF71700041 ER PT J AU GOELZ, MF DIXON, D CLARK, JA MYERS, PH AF GOELZ, MF DIXON, D CLARK, JA MYERS, PH TI DIAGNOSTIC EXERCISE - PLEURAL AND PERITONEAL NODULES IN A FISCHER-344 RAT SO LABORATORY ANIMAL SCIENCE LA English DT Note ID INOCULATION C1 NIEHS,EXPTL PATHOL LAB,RES TRIANGLE PK,NC 27709. RP GOELZ, MF (reprint author), NIEHS,COMPARAT MED BRANCH,POB 12233,RES TRIANGLE PK,NC 27709, USA. FU NCRR NIH HHS [RR00301] NR 8 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD DEC PY 1993 VL 43 IS 6 BP 616 EP 618 PG 3 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA MV091 UT WOS:A1993MV09100017 PM 8158991 ER PT J AU PARSEGIAN, VA AF PARSEGIAN, VA TI RECONCILIATION OF VAN-DER-WAALS FORCE MEASUREMENTS BETWEEN PHOSPHATIDYLCHOLINE BILAYERS IN WATER AND BETWEEN BILAYER-COATED MICA SURFACES SO LANGMUIR LA English DT Article ID ENTROPY-DRIVEN TENSION; PHOSPHOLIPID-BILAYERS; HYDRATION FORCES; FLUID MEMBRANES; LIPID BILAYERS; ATTRACTION; REPULSION; VESICLES AB There is an instructive and simple way to reconcile different measures of van der Waals attraction between phospholipid bilayers. Surface force apparatus (SFA) measurements, qualitatively larger than osmotic stress (OS) and pipet aspiration (PA) results, probably include a dominating contribution from the mica on which bilayers are mounted in the SFA. C1 NIDDK,DIR,MOLEC FORCES SECT,BETHESDA,MD 20892. RP PARSEGIAN, VA (reprint author), NIDDK,DCRT,STRUCT BIOL LAB,BETHESDA,MD 20892, USA. NR 23 TC 27 Z9 27 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0743-7463 J9 LANGMUIR JI Langmuir PD DEC PY 1993 VL 9 IS 12 BP 3625 EP 3628 DI 10.1021/la00036a044 PG 4 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA MN481 UT WOS:A1993MN48100044 ER PT J AU LIU, GY SOBERING, G DUYN, J MOONEN, CTW AF LIU, GY SOBERING, G DUYN, J MOONEN, CTW TI A FUNCTIONAL MRI TECHNIQUE COMBINING PRINCIPLES OF ECHO-SHIFTING WITH A TRAIN OF OBSERVATIONS (PRESTO) SO MAGNETIC RESONANCE IN MEDICINE LA English DT Note DE BRAIN FUNCTION; RAPID MRI; MRI, BLOOD VOLUME; MRI, MAGNETIC SUSCEPTIBILITY ID SENSORY STIMULATION; BRAIN OXYGENATION; NMR; CONTRAST AB We present a fast MRI technique sensitized to microscopic susceptibility effects. The method combines elements of echo-shifted gradient-recalled MR Imaging (TE > TR) with the acquisition of multiple k-space lines within a single TR-period. The sequence results in a much reduced imaging time as compared with conventional gradient-echo MRI methods. The feasibility of the method is demonstrated for susceptibility bolus tracking in the cat brain using an imaging time of 153 ms. The relative cerebral blood volume maps created with this method are comparable with those obtained with conventional methods. C1 NIH,NCRR,BEIP,INVIVO NMR RES CTR,BETHESDA,MD 20892. NIH,DIAGNOST RADIOL RES LAB,BETHESDA,MD 20892. RI Duyn, Jozef/F-2483-2010 NR 27 TC 131 Z9 130 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 DEC PY 1993 VL 30 IS 6 BP 764 EP 768 DI 10.1002/mrm.1910300617 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA MK175 UT WOS:A1993MK17500016 PM 8139461 ER PT J AU AGARWAL, VR SATO, SM AF AGARWAL, VR SATO, SM TI RETINOIC ACID AFFECTS CENTRAL-NERVOUS-SYSTEM DEVELOPMENT OF XENOPUS BY CHANGING CELL FATE SO MECHANISMS OF DEVELOPMENT LA English DT Article DE RETINOIC ACID; XENOPUS; BRAIN; XLPOU 1 ID POSTERIOR AXIS; HENSEN NODE; EMBRYOS; LAEVIS; HINDBRAIN; GENES; TRANSFORMATION; EXPRESSION; PERIOD; STAGE AB Retinoic acid (RA) may play a role in anterior-posterior (A-P) patterning in the central nervous system (CNS) of vertebrates. To understand this role, Xenopus embryos were treated with increasing doses of all-trans RA at the late gastrula to early neurula stage, and changes in the brain were assessed. When embryos were treated with a low dose of 10(-8) M RA, alterations of the brain were observed: a 120% increase in the expression of a neural-specific marker, XlPOU 1, in the brain and eye with a concurrent loss of the forebrain. Higher doses of RA led to progressively more severe truncations in the brain and a loss of XLPOU 1 expression. Most importantly, after observing changes in the RA-treated embryos, we determined that the lineage of cells that contribute to the brain of these embryos do not die but change their fate. With higher doses of RA(greater than or equal to 10(-7) M), the normal cell fate of the A1 lineage was changed from a mostly neuronal phenotype to an epidermal one. Our data suggest that exogenous RA or a closely related derivative causes changes in cell fate of the A1 lineage which may in part be responsible for alterations in the developing CNS. C1 NIDDK,GENET & BIOCHEM BRANCH B10,BETHESDA,MD 20892. NR 29 TC 17 Z9 17 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD DEC PY 1993 VL 44 IS 2-3 BP 167 EP 173 DI 10.1016/0925-4773(93)90065-6 PG 7 WC Developmental Biology SC Developmental Biology GA MQ718 UT WOS:A1993MQ71800008 PM 8155579 ER PT J AU VAIDYA, AB MORRISEY, J PLOWE, CV KASLOW, DC WELLEMS, TE AF VAIDYA, AB MORRISEY, J PLOWE, CV KASLOW, DC WELLEMS, TE TI UNIDIRECTIONAL DOMINANCE OF CYTOPLASMIC INHERITANCE IN 2 GENETIC CROSSES OF PLASMODIUM-FALCIPARUM SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RIBOSOMAL-RNA GENES; MALARIAL PARASITE; MITOCHONDRIAL-DNA; CHLOROQUINE-RESISTANCE; ELECTRON-MICROSCOPE; ASTASIA-LONGA; CIRCULAR DNA; TRANSMISSION; SEQUENCES; GALLINACEUM AB Malarial parasites have two highly conserved cytoplasmic DNA molecules: a 6-kb tandemly arrayed DNA that has characteristics of a mitochondrial genome, and a 35-kb circular DNA that encodes functions commonly found in chloroplasts. We examined the inheritance pattern of these elements in two genetic crosses of Plasmodium falciparum clones. Parent-specific oligonucleotide probes and single-strand conformation polymorphism analysis identified single nucleotide changes that distinguished the parental 6- and 35-kb DNA molecules in the progeny. In all 16 independent recombinant progeny of a cross between a Central American clone, HB3, and a Southeast Asian clone, Dd2, the 6- and 35-kb DNAs were inherited from the Dd2 parent. In all nine independent recombinant progeny of a cross between clone HB3 and a likely African clone, 3D7, the 6-kb DNA was inherited from the 3D7 parent. Inheritance of cytoplasmic genomes of the Dd2 and 3D7 parents was, therefore, dominant over that of the HB3 parent. Cytoplasmic DNA molecules were found almost exclusively in the female gametes of malarial parasites; hence, clone HB3 did not appear to have served as a maternal parent for the progeny of two crosses. Defective differentiation into male gametes by clone Dd2 is likely to be a reason for the cytoplasmic inheritance pattern seen in the HB3 x Dd2 cross. However, incompetence of male or female gametes is unlikely to explain the uniparental dominance in recombinant progeny of the HB3 x 3D7 cross, since both parents readily self-fertilized and completed the malaria life cycle on their own. Instead, the data suggest unidirectional parental incompatibility in cross-fertilization of these malarial parasites, where a usually cosexual parental clone can participate only as a male or as a female. Such an incompatibility may be speculated as indicating an early phase of reproductive isolation of P. falciparum clones from different geographical regions. C1 NIAID,MALARIA RES LAB,BETHESDA,MD 20892. RP VAIDYA, AB (reprint author), HAHNEMANN UNIV,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19102, USA. FU NIAID NIH HHS [AI28398, R01 AI028398] NR 52 TC 45 Z9 46 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1993 VL 13 IS 12 BP 7349 EP 7357 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MJ341 UT WOS:A1993MJ34100016 PM 8246955 ER PT J AU LUEDERS, KK FEWELL, JW MOROZOV, VE KUFF, EL AF LUEDERS, KK FEWELL, JW MOROZOV, VE KUFF, EL TI SELECTIVE EXPRESSION OF INTRACISTERNAL A-PARTICLE GENES IN ESTABLISHED MOUSE PLASMACYTOMAS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID LONG TERMINAL REPEAT; MURINE PLASMACYTOMAS; NUCLEOTIDE-SEQUENCE; PROMOTER ACTIVITY; PROTEIN-BINDING; GENOME; CELLS; ELEMENT; FAMILY; DIFFERENTIATION AB Mouse plasmacytomas generally express higher levels of RNA transcripts from endogenous intracisternal A-particle (IAP) proviral elements than do lipopolysaccharide-stimulated normal lymphocytes. Lymphocytes express a limited and highly characteristic set of IAP elements (lymphocyte-specific [LS] elements). In this study, we examined whether LS elements are expressed at higher levels after transformation of the cells and/or whether new IAP elements are activated. The IAP elements expressed in plasmacytoma MPC11 were characterized by sequence analysis of 22 cDNA clones. The long terminal repeats (LTRs) of the tumor cDNAs proved to be highly related in sequence. None of the clones was of the LS cDNA type. The MPC11 LTRs were five- to sixfold more active than an LS cDNA LTR when tested for promoter activity by transfection into plasmacytoma cells. The LTRs of the tumor-derived cDNAs contained a canonical ATF core sequence (ATF-PC), while the LS cDNAs contained an altered sequence (ATF-LS). An ATF-PC oligonucleotide probe detected multiple IAP transcripts on Northern (RNA) blots of RNA from several plasmacytomas but gave no reaction with RNA from stimulated B lymphocytes. In contrast, an ATF-LS probe detected higher levels of RNA in lymphocyte than in tumor RNAs. Thus, expression of IAP elements in transformed B cells is selective for a different set of regulatory sequence variants than those expressed in normal B cells. Other oligonucleotide probes representing LS- and PC-specific sequence variants detected multiple common hypomethylated IAP proviral loci in three independently derived plasmacytomas. Overall, the results show that established plasmacytomas exhibit a characteristic pattern of IAP proviral hypomethylation and regulatory sequence selection. RP LUEDERS, KK (reprint author), NCI,BIOCHEM LAB,BLDG 37,ROOM 4C-03,BETHESDA,MD 20892, USA. NR 42 TC 32 Z9 32 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 DEC PY 1993 VL 13 IS 12 BP 7439 EP 7446 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MJ341 UT WOS:A1993MJ34100026 PM 8246961 ER PT J AU CAI, H ERHARDT, P TROPPMAIR, J DIAZMECO, MT SITHANANDAM, G RAPP, UR MOSCAT, J COOPER, GM AF CAI, H ERHARDT, P TROPPMAIR, J DIAZMECO, MT SITHANANDAM, G RAPP, UR MOSCAT, J COOPER, GM TI HYDROLYSIS OF PHOSPHATIDYLCHOLINE COUPLES RAS TO ACTIVATION OF RAF PROTEIN-KINASE DURING MITOGENIC SIGNAL-TRANSDUCTION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MOLECULAR-SPECIES ANALYSIS; EPIDERMAL GROWTH-FACTOR; NIH 3T3 CELLS; ALPHA-THROMBIN; PHOSPHOLIPASE-C; MAP KINASE; TYROSINE KINASE; FACTOR RECEPTOR; PC12 CELLS; FIBROBLASTS AB We have investigated the relationship between hydrolysis of phosphatidylcholine (PC) and activation of the Raf-I protein kinase in Ras-mediated transduction of mitogenic signals. As previously reported, cotransfection of a PC-specific phospholipase C (PC-PLC) expression plasmid bypassed the block to cell proliferation resulting from expression of the dominant inhibitory mutant Ras N-17. In contrast, PC-PLC failed to bypass the inhibitory effect of dominant negative Raf mutants, suggesting that PC-PLC functions downstream of Ras but upstream of Raf. Consistent with this hypothesis, treatment of quiescent cells with exogenous PC-PLC induced Raf activation, even when normal Ras function was blocked by Ras N-17 expression. Further, activation of Raf in response to mitogenic growth factors was blocked by inhibition of endogenous PC-PLC. Taken together, these results indicate that hydrolysis of PC mediates Raf activation in response to mitogenic growth factors. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NCI,FREDERICK CANC RES CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. UNIV AUTONOMA MADRID,CSIC,CTR BIOL MOLEC,E-28049 MADRID,SPAIN. RI Moscat, Jorge/A-7011-2009 FU NCI NIH HHS [R01 CA18689] NR 47 TC 128 Z9 128 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 DEC PY 1993 VL 13 IS 12 BP 7645 EP 7651 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MJ341 UT WOS:A1993MJ34100047 PM 8246981 ER PT J AU CEN, H PAPAGEORGE, AG VASS, WC ZHANG, K LOWY, DR AF CEN, H PAPAGEORGE, AG VASS, WC ZHANG, K LOWY, DR TI REGULATED AND CONSTITUTIVE ACTIVITY BY CDC25(MM) (GRF), A RAS-SPECIFIC EXCHANGE FACTOR SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GTPASE-ACTIVATING PROTEIN; TYROSINE KINASE-ACTIVITY; MURINE SARCOMA-VIRUS; SACCHAROMYCES-CEREVISIAE; MEMBRANE ASSOCIATION; ONCOGENE PRODUCTS; CYCLASE PATHWAY; GENE; TRANSFORMATION; P21 AB Serum stimulates cells to increase their proportion of Ras protein in the active GTP-bound state. We have recently identified four types (I to IV of apparently full-length cDNAs from a single mammalian gene, called CDC25Mm or GRF, which is homologous to the Ras-specific exchange factor CDC25 of S. cerevisiae. The largest cDNA (type IV) is brain specific, with the other three classes, although they have distinct 5' ends, essentially representing progressive N-terminal deletions of this cDNA. When placed in a retroviral expression vector, all four types of cDNAs induced morphologic transformation of NIH 3T3 cells and an increase in the basal level of GTP . Ras. Serum stimulation of these transformants lead to a further increase in GTP . Ras only in cells expressing the type IV cDNA. Each type of GRF protein was found in cytosolic and membrane fractions, and the protein in each fraction could stimulate guanine nucleotide release from GDP . Ras in vitro. When NIH 3T3 cells and cells expressing the type IV protein were transfected with two versions of a mutant ras gene, one encoding membrane-associated Ras protein and the other encoding a cytosolic Ras protein, the basal levels of GTP bound to both forms of the mutant Ras protein were significantly higher in the cells expressing the type IV protein. However, serum increased the level of GTP bound to the membrane-associated mutant Ras protein in NIH 3T3 cells and in cells expressing the type IV protein but not in cells expressing the cytosolic version of the Ras protein. We conclude that each type of CDC25Mm induces cell transformation via the ability of its C terminus to stimulate guanine nucleotide exchange on Ras, the presence of N-terminal sequences is associated with a serum-dependent change in GTP . Ras, and the serum-dependent increase in GTP . Ras by exogenous CDC25Mm or by endogenous exchange factors probably requires membrane association of both Ras and the exchange factor. C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. NR 40 TC 47 Z9 47 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 DEC PY 1993 VL 13 IS 12 BP 7718 EP 7724 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MJ341 UT WOS:A1993MJ34100054 PM 8246988 ER PT J AU KOKUBO, T GONG, DW YAMASHITA, S TAKADA, R ROEDER, RG HORIKOSHI, M NAKATANI, Y AF KOKUBO, T GONG, DW YAMASHITA, S TAKADA, R ROEDER, RG HORIKOSHI, M NAKATANI, Y TI MOLECULAR-CLONING, EXPRESSION, AND CHARACTERIZATION OF THE DROSOPHILA 85-KILODALTON TFIID SUBUNIT SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BETA-SUBUNIT; TRANSCRIPTIONAL REGULATION; PREINITIATION COMPLEX; BINDING PROTEIN; HOMOLOGY; YEAST; GENE; IDENTIFICATION; COACTIVATORS; ACTIVATOR AB Transcription initiation factor TFIID is a multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors. To further understand the role of the 85-kDa TFIID subunit (p85), we have cloned the corresponding cDNA with a probe based on an amino acid sequence of the purified protein. The recombinant p85 interacts directly with both the TATA box-binding subunit (TFIIDtau or TBP) and the 110-kDa subunit (p110) of TFIID, suggesting that p85 may play a role in helping to anchor p110 within the TFIID complex and, with other studies, that TFIID assembly and function may involve a concerted series of subunit interactions. Interestingly, the carboxy terminus of p85 contains eight of the WD-40 repeats found originally in the beta subunit of G proteins and more recently in other transcriptional regulatory factors. However, truncated p85 lacking all the WD-40 repeats maintained interactions with both TFIIDtau and p110. These observations leave open the possibility of a distinct function for the WD-40 repeats, possibly in transducing signals by interactions with transcriptional regulators and/or other components of the basic transcriptional machinery. C1 NICHHD,BETHESDA,MD 20892. NINCDS,BETHESDA,MD 20892. ROCKEFELLER UNIV,BIOCHEM & MOLEC BIOL LAB,NEW YORK,NY 10021. UNIV TOKYO,INST MOLEC & CELLULAR BIOSCI,DEV BIOL LAB,BUNKYO KU,TOKYO 113,JAPAN. NR 35 TC 41 Z9 44 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 DEC PY 1993 VL 13 IS 12 BP 7859 EP 7863 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MJ341 UT WOS:A1993MJ34100068 PM 8247000 ER PT J AU DAS, RB BISWAS, R VONDERHAAR, BK AF DAS, RB BISWAS, R VONDERHAAR, BK TI CHARACTERISTICS OF A MEMBRANE-ASSOCIATED ANTILACTOGEN BINDING-SITE FOR TAMOXIFEN SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE PROLACTIN; TAMOXIFEN; ANTILACTOGEN BINDING SITE; LACTOGEN RECEPTOR ID MOUSE MAMMARY-GLAND; HUMAN-BREAST-CANCER; TERM TISSUE-CULTURE; PROLACTIN RECEPTOR; ESTROGEN-RECEPTOR; ANTIESTROGEN; INHIBITION; GROWTH; DNA; IDENTIFICATION AB The antilactogen binding site (ALBS) is a membrane associated protein to which tamoxifen (TAM) and related non-steroidal antiestrogens, but not estrogen, bind. It is through this site that TAM inhibits lactogen binding to the prolactin (Prl) receptor and subsequent Prl induced growth and differentiation in target tissues. Binding of lactogens to the Prl receptor is inhibited by TAM or 4-hydroxy-TAM at 4 degrees C as well as room temperature, thus suggesting that the ALBS is not an enzyme. TAM acts by inhibiting the binding of lactogens to the receptor rather than promoting dissociation of the hormone-receptor complex. Lactogens bind to mammary gland membranes with an K-d of 4.3-8.2 x 10(-10) M. In the presence of 10(-7) M TAM the affinity decreased to a K-d of 0.8-1.6 x 10(-9) M. Binding of H-3-TAM to mammary gland membranes was effectively inhibited by an anti-Prl receptor antibody, thus suggesting a close relationship between the Prl receptor and the ALBS. Separate affinity purification of the ALBS and the Prl receptor resulted in peak fractions demonstrating specific binding activity for both TAM and lactogenic hormones. Re-isolation of the affinity purified Prl receptor on a TAM-Sepharose affinity resin again resulted in co-elution of both binding activities. The isolates from both affinity resins contained primarily a single band with an apparent molecular mass of 90 kDa. This band was precipitated with the anti-Prl receptor antibody and specifically bound the affinity label ring-H-3-TAM aziridine. Lineweaver-Burk analysis of lactogen binding data in the presence and absence. of 10(-7) M TAM suggests that this drug is a competitive inhibitor of the hormone binding. Taken together these data suggest that the ALBS may be one form of the Prl receptor and that TAM and the lactogenic hormones may share a common binding site. C1 NCI, TUMOR IMMUNOL & BIOL LAB, BETHESDA, MD 20892 USA. NR 45 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD DEC PY 1993 VL 98 IS 1 BP 1 EP 8 PG 8 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA MR584 UT WOS:A1993MR58400001 PM 8143909 ER PT J AU VAMVAKOPOULOS, NO AF VAMVAKOPOULOS, NO TI TISSUE-SPECIFIC EXPRESSION OF HEAT-SHOCK PROTEIN-70 AND PROTEIN-90 - POTENTIAL IMPLICATION FOR DIFFERENTIAL SENSITIVITY OF TISSUES TO GLUCOCORTICOIDS SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE TISSUE-SPECIFIC EXPRESSION; HEAT SHOCK PROTEIN 70/90 SYSTEM; DIFFERENTIAL TISSUE SENSITIVITY TO GLUCOCORTICOIDS ID RECEPTOR MESSENGER-RNA; STRESS PROTEINS; GENE FAMILY; CELL; TRANSCRIPTION; DEXAMETHASONE; PROMOTER; SEQUENCE; BINDING; ELEMENT AB Heat shock proteins (hsps) and glucocorticoids are key elements of the organism's adaptive response to adverse physiological conditions. Glucocorticoids are pleiotropic hormones acting through receptor-mediated processes and eliciting tissue-specific biologic effects. The inactive form of the glucocorticoid receptor (GR) in the cytoplasm appears to be bound to hsps of the 90K family (hsp90 alpha and hsp90 beta). This interaction facilitates binding of glucocorticoid to its receptor, and depends on the relative amounts of the interacting components, GR and hsp90. To gain insight into the mechanisms of glucocorticoid regulation in a physiological context, the level of the hsp70/90 system in a panel of tissues, including testis, spleen, liver, thymus, pituitary, hypothalamus, hippocampus, brain cortex, pineal and adrenal, was examined by Western blotting. The hsp90 component showed greater variation (up to about forty-fold) relative to the less variable (up to about three-fold) hsp70 component of the system. The relative distribution of the hsp90 alpha and beta forms in the various tissues was also examined by a combination of Western and Northern blotting techniques. It was found that the alpha form predominated in the brain and the testis and the beta form predominated in the other peripheral organs. There was no relation between tissue hsp90 content and differential expression of either form. These findings suggest that tissue hsp90 content, an important physiological parameter of cellular homeostasis, may confer tissue specificity and sensitivity to glucocorticoids. RP VAMVAKOPOULOS, NO (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N-240,BETHESDA,MD 20892, USA. NR 46 TC 54 Z9 58 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD DEC PY 1993 VL 98 IS 1 BP 49 EP 54 DI 10.1016/0303-7207(93)90235-C PG 6 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA MR584 UT WOS:A1993MR58400007 PM 8143913 ER PT J AU FERREIRA, A KINCAID, R KOSIK, KS AF FERREIRA, A KINCAID, R KOSIK, KS TI CALCINEURIN IS ASSOCIATED WITH THE CYTOSKELETON OF CULTURED NEURONS AND HAS A ROLE IN THE ACQUISITION OF POLARITY SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID CALMODULIN-BINDING-PROTEIN; MICROTUBULE-ASSOCIATED PROTEINS; CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE; GROWTH CONES; ACTIN-FILAMENTS; TAU-FACTOR; CEREBELLAR MACRONEURONS; HIPPOCAMPAL-NEURONS; MAMMALIAN BRAIN; PHOSPHORYLATION AB Calcineurin is a calmodulin-dependent serine-threonine phosphatase found in many cell types but most abundant in neurons. To determine its localization in developing neurons, dissociated cultures from embryonic day 15 rat cerebellum were analyzed immunocytochemically after treatment with cytoskeletal-disrupting drugs. During the initial outgrowth of neurites, calcineurin is enriched in growth cones where its localization depends upon the integrity of both microtubules and actin filaments. Treatment with cytochalasin shifts calcineurin from the growth cone to the neurite shaft, and with nocadozole calcineurin translocates to the cell body. Therefore calcineurin is well positioned to mediate interactions between cytoskeletal systems during neurite elongation. By 14 d in culture, when the neurons have developed extensive neuronal contacts and synapses are present, calcineurin is predominantly in the neurite shaft. Incubation of cultured cells with Cyclosporin A or a specific peptide, both of which selectively inhibit calcineurin's phosphatase activity, prevented axonal elongation. Because the microtubule-associated protein tau appears to play a key role in asymmetric neurite elongation, we examined modifications in its phosphorylation state resulting from calcineurin inhibition. In contrast to the normal development of cerebellar macroneurons in which reactivity with the phosphorylation-dependent antibody, tau-l, progressively increases, there was a persistent inhibition of tau-l reactivity in cells exposed to Cyclosporin A. These findings suggest a role for calcineurin in regulating tau phosphorylation and possibly modulating other steps required for the determination of polarity. C1 BRIGHAM & WOMENS HOSP,CTR NEUROL DIS,BOSTON,MA 02115. NIAAA,IMMUNOL SECT,MOLEC & CELLULAR NEUROBIOL LAB,ROCKVILLE,MD 20852. RP FERREIRA, A (reprint author), HARVARD UNIV,SCH MED,DEPT MED,DIV NEUROL,BOSTON,MA 02115, USA. FU NIA NIH HHS [AG-06601]; NINDS NIH HHS [NS-29031] NR 76 TC 89 Z9 90 U1 0 U2 5 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1993 VL 4 IS 12 BP 1225 EP 1238 PG 14 WC Cell Biology SC Cell Biology GA MU413 UT WOS:A1993MU41300001 PM 8167406 ER PT J AU HINNEBUSCH, J TILLY, K AF HINNEBUSCH, J TILLY, K TI LINEAR PLASMIDS AND CHROMOSOMES IN BACTERIA SO MOLECULAR MICROBIOLOGY LA English DT Review ID SWINE FEVER VIRUS; BORRELIA-BURGDORFERI; LYME-DISEASE; HAIRPIN ENDS; DNA; GENES; REPLICATION; EXPRESSION; TELOMERE; SEQUENCE AB Linear plasmids and chromosomes were unknown in prokaryotes until recently but have now been found in spirochaetes, Gram-positive bacteria, and Gram-negative bacteria. Two structural types of bacterial linear DNA have been characterized. Linear plasmids of the spirochaete Borrelia have a covalently closed hairpin loop at each end and linear plasmids of the Gram-positive filamentous Streptomyces have a covalently attached protein at each end. Replicons with similar structures are more frequent in eukaryotic cells than in prokaryotes. Linear genomic structures are probably more common in bacteria than previously recognized, however, and some replicons may interconvert between circular and linear isomers. The molecular biology of these widely dispersed elements provides clues to explain the origin of linear DNA in bacteria, including evidence for genetic exchange between prokaryotes and eukaryotes. C1 NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840. RP HINNEBUSCH, J (reprint author), NIAID,ROCKY MT LABS,VECTORS & PATHOGENS LAB,HAMILTON,MT 59840, USA. NR 60 TC 102 Z9 103 U1 1 U2 17 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD DEC PY 1993 VL 10 IS 5 BP 917 EP 922 DI 10.1111/j.1365-2958.1993.tb00963.x PG 6 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA MM635 UT WOS:A1993MM63500003 PM 7934868 ER PT J AU KRIEGER, C HANSEN, S HEYES, MP AF KRIEGER, C HANSEN, S HEYES, MP TI AMYOTROPHIC-LATERAL-SCLEROSIS - QUINOLINIC ACID LEVELS IN CEREBROSPINAL-FLUID AND SPINAL-CORD SO NEURODEGENERATION LA English DT Article DE AMYOTROPHIC LATERAL SCLEROSIS; CEREBROSPINAL FLUID; HUNTINGTONS CHOREA; OLIVOPONTOCEREBELLAR ATROPHY; QUINOLINIC ACID ID INHERITED OLIVOPONTOCEREBELLAR ATROPHY; HUNTINGTONS-DISEASE; RAT-BRAIN; KYNURENINE; METABOLISM; LESIONS; SYSTEM C1 UNIV BRITISH COLUMBIA,DEPT MED,DIV NEUROL,VANCOUVER V6T 1W5,BC,CANADA. UNIV BRITISH COLUMBIA,DEPT PHARMACOL & THERAPEUT,VANCOUVER V6T 1W5,BC,CANADA. NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,BETHESDA,MD 20892. NR 27 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1055-8330 J9 NEURODEGENERATION JI Neurodegeneration PD DEC PY 1993 VL 2 IS 4 BP 237 EP 241 PG 5 WC Neurosciences SC Neurosciences & Neurology GA MW378 UT WOS:A1993MW37800003 ER PT J AU CHARNAS, LR MARINI, JC AF CHARNAS, LR MARINI, JC TI COMMUNICATING HYDROCEPHALUS, BASILAR INVAGINATION, AND OTHER NEUROLOGIC FEATURES IN OSTEOGENESIS IMPERFECTA SO NEUROLOGY LA English DT Article ID TRANSGENIC MICE; IMPRESSION; ACHONDROPLASIA; MANAGEMENT; PHENOTYPE; FORM; GENE AB Osteogenesis imperfecta (OI) is anecdotally associated with macrocephaly, hydrocephalus, basilar invagination, and cerebral atrophy, but the frequency and the spectrum of neurologic features of this condition are poorly defined. We report our experience with 76 patients with OI seen at NIH. Neuroimaging studies demonstrated sulcal prominence and ventriculomegaly consistent with communicating hydrocephalus in 17 patients. Eight individuals with severe OI types displayed basilar invagination, causing brainstem compression in three patients. Head circumference growth showed abnormal kinetics with percentile crossing after fontanelle closure in 13 patients, and absolute macrocephaly was present in 11 patients. Additional neurologic complications included skull fracture (10 individuals); seizure disorders (five); transient, unexplained long tract signs (three); and spinal compression and pontine, cervical, and thoracic syringohydromyelia (one patient each). The clinically important neurologic complications appear to be brainstem compression from basilar invagination, skull fracture, and seizure disorders. Neurologic evaluation should be part of a team approach in the management of patients with severe OI types. C1 NICHHD,HUMAN GENET BRANCH,CONNECT TISSUE DISORDERS SECT,BETHESDA,MD 20892. RP CHARNAS, LR (reprint author), NICHHD,HUMAN GENET BRANCH,NEUROGENET UNIT,BLDG 10,ROOM 9S242,BETHESDA,MD 20892, USA. NR 37 TC 49 Z9 49 U1 0 U2 2 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 1993 VL 43 IS 12 BP 2603 EP 2608 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA MM324 UT WOS:A1993MM32400032 PM 8255464 ER PT J AU NISHIMURA, M MCFARLIN, DE JACOBSON, S AF NISHIMURA, M MCFARLIN, DE JACOBSON, S TI SEQUENCE COMPARISONS OF HTLV-I FROM HAM TSP PATIENTS AND THEIR ASYMPTOMATIC SPOUSES SO NEUROLOGY LA English DT Article ID T-CELL LEUKEMIA; VIRUS TYPE-I; TROPICAL SPASTIC PARAPARESIS; COMPLETE NUCLEOTIDE-SEQUENCE; POLYMERASE CHAIN-REACTION; CYTOTOXIC LYMPHOCYTES-T; ENZYMATIC AMPLIFICATION; MYELOPATHY; DNA; PROVIRUS AB We amplified and sequenced portions of the human T-lymphotropic virus type I (HTLV-I) (U3), pol, env, and pX provirus regions (1212 bp per person) from peripheral blood lymphocytes (PBL) of two married couples (case 1 and case 2). Both husbands are patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and the wives are asymptomatic HTLV-I carriers. We selected these regions because the LTR and env regions of murine retrovirus models have been involved in determining tissue tropism. In addition, the predominant immunogenic epitope for HTLV-I-specific cytotoxic T cells obtained from circulating PBL of HAM/TSP patients was localized in the HTLV-I pX region. Our aim was to examine variations in these HTLV-I regions between affected and asymptomatic spouses. In the HTLV-I regions studied, we detected no sequence variation between each couple. These data do not favor the hypothesis that neurotropic mutants of HTLV-I are involved in the pathogenesis of HAM/TSP. C1 NIH,NEUROIMMUNOL BRANCH,BLDG 10,ROOM 5B-16,BETHESDA,MD 20892. UTANO NATL HOSP,CLIN RES CTR,NARUTAKI UKYO KU,KYOTO,JAPAN. NR 32 TC 13 Z9 13 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 DEC PY 1993 VL 43 IS 12 BP 2621 EP 2624 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA MM324 UT WOS:A1993MM32400035 PM 7504797 ER PT J AU ROBERTS, JW CORALOCATELLI, G BRAVI, D AMANTEA, MA MOURADIAN, MM CHASE, TN AF ROBERTS, JW CORALOCATELLI, G BRAVI, D AMANTEA, MA MOURADIAN, MM CHASE, TN TI CATECHOL-O-METHYLTRANSFERASE INHIBITOR TOLCAPONE PROLONGS LEVODOPA CARBIDOPA ACTION IN PARKINSONIAN-PATIENTS SO NEUROLOGY LA English DT Article ID DOUBLE-BLIND; SINEMET CR4; RO 40-7592; DISEASE; DOPAMINE; FLUCTUATIONS; MECHANISMS; CROSSOVER; RATS AB The wearing-off phenomenon frequently complicates levodopa therapy of Parkinson's disease (PD). These response fluctuations appear when intrasynaptic dopamine concentrations begin to reflect the swings in levodopa availability that attend standard dosing regimens. Drugs that prolong the biologic half-life of levodopa and dopamine should thus prove beneficial. We administered levodopa/carbidopa in combination with single oral doses of tolcapone (Ro 40-7592), an inhibitor of catechol-0-methyltransferase, under controlled conditions to 10 PD patients with the wearing-off phenomenon. Tolcapone prolonged the antiparkinson response to levodopa/carbidopa by about 67% at several doses ranging from 50 to 400 mg (p < 0.05). There was no significant change in the peak levodopa effect on parkinsoinan signs or in the severity of dyskinesias. No dose-limiting adverse effects occurred. Multiple daily dosing with tolcapone would thus be expected to safe reduce the wearing-off phenomenon associated with levodopa/carbidopa therapy. C1 NINCDS,EXPTL THERAPEUT BRANCH,BLDG 10,ROOM 5C103,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT PHARM,PHARMACEUT DEV SERV,PHARMACOKINET LAB,BETHESDA,MD 20892. OI Mouradian, M. Maral/0000-0002-9937-412X NR 16 TC 70 Z9 70 U1 1 U2 4 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 1993 VL 43 IS 12 BP 2685 EP 2688 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA MM324 UT WOS:A1993MM32400048 PM 8255478 ER PT J AU PARTIN, KM PATNEAU, DK WINTERS, CA MAYER, ML BUONANNO, A AF PARTIN, KM PATNEAU, DK WINTERS, CA MAYER, ML BUONANNO, A TI SELECTIVE MODULATION OF DESENSITIZATION AT AMPA VERSUS KAINATE RECEPTORS BY CYCLOTHIAZIDE AND CONCANAVALIN-A SO NEURON LA English DT Article ID METHYL-D-ASPARTATE; GLUTAMATE-OPERATED CHANNELS; MOLECULAR-CLONING; GLIAL-CELLS; PHARMACOLOGICAL PROPERTIES; STRUCTURAL DETERMINANTS; FUNCTIONAL EXPRESSION; QUISQUALATE RECEPTORS; GANGLION NEURONS; XENOPUS-OOCYTES AB Potentiation by cyclothiazide of recombinant glutamate receptor responses in Xenopus oocytes showed absolute selectivity for AMPA versus kainate receptors. In contrast, concanavalin A strongly potentiated responses at kainate but not AMPA receptors. Rapid desensitization in HEK 293 cells transfected with AMPA receptors was blocked by cyclothiazide, but only weakly attenuated by concanavalin A. Desensitization at kainate receptors was blocked by concanavalin A but unaffected by cyclothiazide. Selective effects of these modulators following coexpression of subunits from different families suggest independent assembly of functional AMPA and kainate receptors. Northern biot analysis of mRNA for dorsal root ganglia revealed a predominant expression of GluR5, indicating that modulation of desensitization by concanavalin A but not cyclothiazide in sensory neurons accurately predicts subunit expression for native glutamate receptors. C1 NICHHD,DEV NEUROBIOL,BETHESDA,MD 20892. RP PARTIN, KM (reprint author), NICHHD,CELLULAR & MOLEC NEUROPHYSIOL LAB,BETHESDA,MD 20892, USA. RI Mayer, Mark/H-5500-2013; Partin, Kathryn/A-8706-2015 OI Partin, Kathryn/0000-0003-3801-3299 NR 52 TC 491 Z9 494 U1 0 U2 13 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD DEC PY 1993 VL 11 IS 6 BP 1069 EP 1082 DI 10.1016/0896-6273(93)90220-L PG 14 WC Neurosciences SC Neurosciences & Neurology GA MP548 UT WOS:A1993MP54800008 PM 7506043 ER PT J AU BAUMANN, MH RUTTER, JJ AUERBACH, SB AF BAUMANN, MH RUTTER, JJ AUERBACH, SB TI INTRAVENOUS ADMINISTRATION OF THE SEROTONIN AGONIST M-CHLOROPHENYLPIPERAZINE (MCPP) INCREASES EXTRACELLULAR SEROTONIN IN THE DIENCEPHALON OF AWAKE RATS SO NEUROPHARMACOLOGY LA English DT Article DE MICRODIALYSIS; SEROTONIN; MCPP; FLUOXETINE; PROLACTIN; PRESYNAPTIC ID META-CHLOROPHENYLPIPERAZINE; 5-HT1C RECEPTORS; NEURO-ENDOCRINE; BINDING-SITES; TFMPP; BRAIN; ANTAGONISTS; RELEASE; HUMANS; ARYLPIPERAZINES AB The serotonin (5-HT) agonist 1-(-m-chlorophenyl)piperazine (mCPP) has been widely used as a pharmacological probe to assess 5-HT function. Although mCPP is known to interact with 5-HT receptors, this drug is also reported to exhibit presynaptic actions that increase extraneuronal 5-HT in vitro. In the present study, we used in vivo microdialysis to examine the effects of mCPP on extracellular 5-HT in the ventromedial diencephalon of awake rats. Intravenous mCPP (1.0 and 2.0 mg/kg) increased dialysate 5-HT in a dose-related manner, with extracellular 5-HT levels rising I-fold above baseline after the high dose of drug. The stimulatory effect of mCPP on dialysate 5-HT was abolished by pretreatment with the 5-HT uptake blocker fluoxetine (10 mg/kg, i.p.). In complementary experiments, mCPP elevated plasma prolactin at doses equivalent to those that increased dialysate 5-HT, and fluoxetine pretreatment caused a partial, though significant, attenuation of mCPP-induced prolactin release. These results indicate that mCPP increases extracellular 5-HT in rat brain by a presynaptic mechanism involving 5-HT transporters. Moreover, the plasma prolactin response to mCPP is at least partially mediated by the presynaptic actions of the drug. Our data further suggest the possibility that mCPP exhibits indirect agonist properties in human brain. Therefore, clinical studies designed to evaluate postsynaptic 5-HT receptor sensitivity based on responsiveness to mCPP should be interpreted with caution. C1 RUTGERS UNIV,DEPT BIOL SCI,PISCATAWAY,NJ 08855. RP BAUMANN, MH (reprint author), NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,POB 5180,BALTIMORE,MD 21224, USA. NR 37 TC 55 Z9 56 U1 1 U2 1 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 DEC PY 1993 VL 32 IS 12 BP 1381 EP 1386 DI 10.1016/0028-3908(93)90034-Z PG 6 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA MP680 UT WOS:A1993MP68000012 PM 8152528 ER PT J AU BRAUN, AR STOETTER, B RANDOLPH, C HSIAO, JK VLADAR, K GERNERT, J CARSON, RE HERSCOVITCH, P CHASE, TN AF BRAUN, AR STOETTER, B RANDOLPH, C HSIAO, JK VLADAR, K GERNERT, J CARSON, RE HERSCOVITCH, P CHASE, TN TI THE FUNCTIONAL NEUROANATOMY OF TOURETTES-SYNDROME - AN FDG-PET STUDY .1. REGIONAL CHANGES IN CEREBRAL GLUCOSE-METABOLISM DIFFERENTIATING PATIENTS AND CONTROLS SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE TOURETTES SYNDROME; POSITRON-EMISSION TOMOGRAPHY; (18)[F]-FLUORODEOXYGLUCOSE; MOVEMENT DISORDERS; BASAL GANGLIA; PREMOTOR; MOTOR; LIMBIC ID DE-LA-TOURETTE; OBSESSIVE-COMPULSIVE DISORDER; SUPPLEMENTARY MOTOR CORTEX; ELECTRICAL-STIMULATION; VENTRAL PALLIDUM; CHILDHOOD-ONSET; GILLES; ORGANIZATION; COMPONENTS; MOVEMENT AB Regional metabolic rates for glucose estimated using [F-18]fluorodeoxyglucose positron-emission tomography were compared in 16 drug-free patients with Tourette's syndrome (TS) and 16 age- and sex-matched normal volunteers. Tourette's syndrome patients were characterized by decreased normalized metabolic rates in paralimbic and ventral prefrontal cortices, particularly in orbitofrontal, inferior insular, and parahippocampal regions. Similar decreases were observed in subcortical regions, including the ventral striatum (nucleus accumbens/ventromedial caudate) and in the midbrain, These changes were more robust and occurred with greater frequency in the left hemisphere. They were associated with concomitant bilateral increases in metabolic activity the supplementary motor, lateral premotor, and Rolandic cortices. Effects of prior exposure to neuroactive drugs did not account for these findings. These results suggest that an altered relationship between limbic-related regions of the cortex and striatum and cortical regions involved in the initiation of movement may play a role in the pathogenesis of this illness. C1 NIND,EXPTL THERAPEUT BRANCH,BETHESDA,MD. NIMH,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT PET,BETHESDA,MD 20892. ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. GEORGE WASHINGTON UNIV,DEPT PSYCHOL,WASHINGTON,DC 20052. RP BRAUN, AR (reprint author), NIDCD,VOICE SPEECH & LANGUAGE BRANCH,VOICE & SPEECH SECT,NEUROIMAGING UNIT,BLDG 10,ROOM 5D38,BETHESDA,MD 20892, USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 65 TC 120 Z9 121 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 1993 VL 9 IS 4 BP 277 EP 291 PG 15 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA MJ727 UT WOS:A1993MJ72700004 PM 8305128 ER PT J AU ESHHAR, N PETRALIA, RS WINTERS, CA NIEDZIELSKI, AS WENTHOLD, RJ AF ESHHAR, N PETRALIA, RS WINTERS, CA NIEDZIELSKI, AS WENTHOLD, RJ TI THE SEGREGATION AND EXPRESSION OF GLUTAMATE-RECEPTOR SUBUNITS IN CULTURED HIPPOCAMPAL-NEURONS SO NEUROSCIENCE LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTOR; MICROTUBULE-ASSOCIATED PROTEIN-2; DISPERSED CELL-CULTURE; AMINO-ACID RECEPTORS; METHYL-D-ASPARTATE; RAT-BRAIN; IMMUNOCYTOCHEMICAL LOCALIZATION; COATED VESICLES; ULTRASTRUCTURAL IMMUNOCYTOCHEMISTRY; OPERATED CHANNELS AB The distribution and expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate-selective glutamate receptor subunits (GluRl-4) were studied in cultured hippocampal neurons using antibodies generated against peptides corresponding to the C-termini of GluR1-4, GluR2/3 and GluR4, and with a set of oligonucleotide probes designed complementary to specific pan, flip and flop GluR1-4 messenger RNA sequences. GluR1-4 subunit proteins were localized in fixed hippocampal neurons (2 h to three weeks after plating) by immunocytochemistry with light and electron microscopy. At early stages in culture, moderate staining with antibodies to GluR1 and GluR2/3 and very light staining with antibody to GluR4 was observed in cell bodies and proximal portions of all neurites of some neurons. Upon establishment Of identified axons and dendrites by seven days in culture, staining was intense with specific antibodies to GluR1 and GluR2/3 and light with anti-GluR4 antibody in cell bodies and dendrites. Little or no staining was observed in axons. Cells at seven days in culture exhibited a variety of morphologies. However, we could not assign a pattern of staining to a particular type. As the cultures matured over two and three weeks, staining was limited to the somatodendritic compartment. The intensity of glutamate receptor subunit staining increased and the extent of staining proceeded to the distal extreme of many dendrites. Moreover, antibodies to GluR1-4 subunits were co-localized in neurons. Immunocytochemistry on living neurons did not result in any significant labeling, suggesting that the epitope is either not expressed on the surface of the neurons, or is present, but inaccessible to the antibody. Election microscopy demonstrated receptor localization similar to that found in brain, with staining of postsynaptic membrane and density, dendritic cytoplasm and cell body, but not within the synaptic cleft. We examined the possible role of ''cellular compartmentation'' in the pattern of glutamate receptor expression in hippocampal neurons. Compartmentalization studies of the subcellular distribution of messenger RNAs encoding GluR1-4 subunits was determined in mature cultures by in situ hybridization. Significant silver grain appearance was restricted to the cell body, indicating that the synthesis of glutamate receptor subunits is limited largely to the neuronal cell body. The expression of microtubule-associated protein 2 was studied in parallel. Microtubule-associated protein 2 expression appeared 6 h after plating, while glutamate receptor subunit expression was present at 2 h. This indicates that microtubule-associated protein 2 does not regulate the initial distribution of glutamate receptor subunits into neurites. Restriction of expression to the cell body raises important questions concerning the mechanisms governing the transport of GluR proteins to their appropriate compartments within neurons of the developing and mature nervous system. C1 NIDCD,NEUROCHEM LAB,BETHESDA,MD 20892. NICHHD,CELLULAR & MOLEC NEUROPHYSIOL LAB,BETHESDA,MD 20892. NR 80 TC 61 Z9 61 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD DEC PY 1993 VL 57 IS 4 BP 943 EP 964 DI 10.1016/0306-4522(93)90040-M PG 22 WC Neurosciences SC Neurosciences & Neurology GA ML366 UT WOS:A1993ML36600010 PM 8309554 ER PT J AU YASUI, M OTA, K GARRUTO, RM AF YASUI, M OTA, K GARRUTO, RM TI CONCENTRATIONS OF ZINC AND IRON IN THE BRAINS OF GUAMANIAN PATIENTS WITH AMYOTROPHIC-LATERAL-SCLEROSIS AND PARKINSONISM-DEMENTIA SO NEUROTOXICOLOGY LA English DT Article DE ZINC; IRON; CENTRAL NERVOUS SYSTEM; NEUTRON ACTIVATION ANALYSIS; ELEMENTAL INTERACTION ID CENTRAL-NERVOUS-SYSTEM; DISEASE; CALCIUM; PATHOGENESIS; DISORDERS; NEURONS; PACIFIC; TISSUES; BONES; GUAM AB Simultaneous measurements of zinc (Zn) and iron (Fe) concentrations were determined using neutron activation analysis in gray and white matter of the frontal and occipital regions obtained from four patients with parkinsonism-dementia (PD), eight with amyotrophic lateral sclerosis (ALS), and four neurologically normal controls from Guam. Zn content in gray matter from the frontal cortex in ALS and PD cases was significantly decreased, compared with that of controls (p<0.05). No significant differences were found in the Zn content of white matter from the frontal cortex, and/or gray and white matter from the occipital cortex between the groups. The Zn content in gray matter from both frontal and occipital regions was less in ALS and PD patients than in controls. Fe content in gray matter from the frontal cortex of ALS and PD increased significantly compared with that of controls (p<0.05). Fe content in white matter from the frontal cortex in PD patients was greater than in controls (p<0.05), with an overall difference: controls < ALS < PD. These data indicate that an increase in Fe in gray and white matter, and a decrease concentration of Zn in gray matter combined with an excess and deficiency of bioavailable aluminum and calcium, respectively, may be involved in the pathogenic process of these disorders. (C) 1993 Intox Press, Inc. C1 WAKAYAMA MED COLL,DEPT LAB MED,WAKAYAMA 640,JAPAN. NATL INST HLTH,CENT NERVOUS SYST STUDIES LAB,BETHESDA,MD 20892. RP YASUI, M (reprint author), WAKAYAMA MED COLL,DIV NEUROL DIS,WAKAYAMA 640,JAPAN. NR 26 TC 32 Z9 33 U1 0 U2 0 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD WIN PY 1993 VL 14 IS 4 BP 445 EP 450 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA MT959 UT WOS:A1993MT95900009 PM 8164889 ER PT J AU CLARK, SL FREDERIKSEN, MC JACOBS, MM KAUFFMAN, R LUSKIN, AT MCNELLIS, D MYERS, D NELSON, HS SCHATZ, M SCIALLI, AR WISE, RA PARKER, SR TAGGERT, VS AF CLARK, SL FREDERIKSEN, MC JACOBS, MM KAUFFMAN, R LUSKIN, AT MCNELLIS, D MYERS, D NELSON, HS SCHATZ, M SCIALLI, AR WISE, RA PARKER, SR TAGGERT, VS TI ASTHMA IN PREGNANCY SO OBSTETRICS AND GYNECOLOGY LA English DT Note AB This manuscript is a summary of a comprehensive report dealing with asthma and pregnancy issued by the working group on Asthma and Pregnancy, National Institutes of Health (NIH), National Heart, Lung, and Blood Institute. The report was developed by a panel of obstetricians, pharmacologists, internists, allergists, and pulmonologists, who met over an 18-month period under the auspices of the NIH. Undertreatment of pregnant asthmatics, partially because of unfounded fears of adverse pharmacologic effects on the developing fetus, remains the major problem in the management of asthma during pregnancy in the United States. The four key components of asthma management during pregnancy are: 1) objective assessment of maternal lung function and fetal well-being, 2) avoidance or control of environmental precipitating factors, 3) pharmacologic therapy, and 4) patient education. C1 NIH,BETHESDA,MD 20892. UNIV UTAH,SCH MED,DEPT OBSTET & GYNECOL,SALT LAKE CITY,UT 84112. OI Wise, Robert/0000-0002-8353-2349 NR 0 TC 42 Z9 42 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 1993 VL 82 IS 6 BP 1036 EP 1040 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA MH769 UT WOS:A1993MH76900028 PM 8233255 ER PT J AU BUSCHER, D DELLOSBARBA, P HIPSKIND, RA RAPP, UR STANLEY, ER BACCARINI, M AF BUSCHER, D DELLOSBARBA, P HIPSKIND, RA RAPP, UR STANLEY, ER BACCARINI, M TI V-RAF CONFERS CSF-1 INDEPENDENT GROWTH TO A MACROPHAGE CELL-LINE AND LEADS TO IMMEDIATE-EARLY GENE-EXPRESSION WITHOUT MAP-KINASE ACTIVATION SO ONCOGENE LA English DT Article ID STIMULATING FACTOR-I; RECOMBINANT MURINE RETROVIRUS; PROTEIN-KINASE; C-FOS; SIGNAL TRANSDUCTION; PHOSPHATIDYLINOSITOL 3-KINASE; TRANSCRIPTIONAL ACTIVATION; BINDING-SITES; BONE-MARROW; RECEPTOR AB The BAC-1.2F5 macrophage cell line depends on CSF-1 for proliferation and survival. Phosphorylation and activation of the RAF-1 kinase are among the early events in CSF-1 signal transduction. To characterize the role of RAF-1 in CSF-1-induced proliferation, we overexpressed oncogenically activated RAF-1, cellular RAF-1 and RAF-1 kinase-defective mutant proteins in BAC-1.2F5 cells. We were unable to establish stable cell lines expressing either kinase-negative or full length RAF-1 proteins, implying that expression of these molecules is not tolerated in BAC-1.2F5 cells. Oncogenically activated RAF-1 induces CSF-1-independent growth in the absence of autocrine growth factor production. Autonomous growth is not associated with dedifferentiation, since v-raf-expressing macrophages perform the same immunological functions as control cells. Intriguingly, autonomous growth correlates with the suppression of CSF-1-mediated MAP-Kinase activation and with the low constitutive expression of a number of CSF-1-inducible genes, including fos, jun, ets2, and myc, but also the genes for the inflammatory cytokines TNF alpha and IL-1 beta. Many of these genes have AP-1 binding sites in their promoters, and the v-raf-expressing cells contain constitutive AP-1 binding activity. These data indicate that RAF-1, but not MAP-Kinase, is a key component in CSF-1 mitogenic signal transduction, and are consistent with a working hypothesis in which RAF-1 mediates transcriptional activation of genes via AP-1. C1 FRAUNHOFER INST TOXICOL & MOLEC BIOL,DEPT IMMUNBIOL,HANNOVER,GERMANY. INST MOLEC BIOL,HANNOVER,GERMANY. UNIV FLORENCE,INST GEN PATHOL,FLORENCE,ITALY. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. ALBERT EINSTEIN COLL MED,DEPT DEV & MOLEC BIOL,BRONX,NY 10461. RI Baccarini, Manuela/B-6481-2014 OI Baccarini, Manuela/0000-0002-3033-391X FU NCI NIH HHS [CA 26504] NR 73 TC 52 Z9 52 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC PY 1993 VL 8 IS 12 BP 3323 EP 3332 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA MG782 UT WOS:A1993MG78200016 PM 8247534 ER PT J AU PICHEL, JG LAKSO, M WESTPHAL, H AF PICHEL, JG LAKSO, M WESTPHAL, H TI TIMING OF SV40 ONCOGENE ACTIVATION BY SITE-SPECIFIC RECOMBINATION DETERMINES SUBSEQUENT TUMOR PROGRESSION DINING MURINE LENS DEVELOPMENT SO ONCOGENE LA English DT Article ID TRANSGENIC MICE; ANTIGEN EXPRESSION; DNA RECOMBINATION; MAMMALIAN-CELLS; MOUSE LENS; GENE; CRYSTALLIN; PROMOTER; DIFFERENTIATION; TUMORIGENESIS AB We generated mice that carry copies of a dormant transgene encoding the SV40 tumor antigens. The transgenes are specifically targeted to the lens and contain features that render their expression dependent on the action of Cre, a site-specific bacteriophage DNA recombinase. Timing of oncogene activation was controlled by making Cre available either prior to, or coincident with, the onset of primary fiber differentiation in the embryonic lens vesicle. Early expression of Cre resulted in oncogene activation in undifferentiated lens epithelial cells that rapidly proliferated inside the lens capsule. By contrast, when Cre accumulation was delayed to coincide with the onset of primary lens fiber differentiation, SV40 oncogenes were activated in cells that had begun to elongate and to accumulate lens-specific crystallins. During subsequent proliferation inside the lens capsule, transformed progeny cells maintained the profile of fiber differentiation that their parent cells had acquired at the time of oncogenic conversion. Developing lens tumors were confined within the capsule of the embryonic lens. However, if the capsule was perforated in an embryonic eye in organ culture, cells rapidly grew out while still maintaining features of differentiation. Our findings show that the differentiated state of the primary target cells is an important parameter of subsequent lens oncogenesis, and that an intact lens capsule can restrict invasive neoplastic growth. C1 NICHHD,MAMMALIAN GENES & DEV LAB,BETHESDA,MD 20892. NR 28 TC 21 Z9 21 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC PY 1993 VL 8 IS 12 BP 3333 EP 3342 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA MG782 UT WOS:A1993MG78200017 PM 8247535 ER PT J AU CAUDLE, RM WILLIAMS, GM AF CAUDLE, RM WILLIAMS, GM TI THE MISUSE OF ANALYSIS OF VARIANCE TO DETECT SYNERGY IN COMBINATION-DRUG STUDIES SO PAIN LA English DT Article DE ANALYSIS OF VARIANCE; SYNERGY; DOSE RESPONSE; ISOBOLOGRAPHIC ANALYSIS; STATISTICS AB Drug combination studies often examine the possibility of synergy between drugs. Synergy is defined as an effect of a combination of drugs greater than that expected from the effects of the drugs given individually. One technique used by several investigators is the use of analysis of variance (ANOVA) to determine synergy. In this discussion, the argument is made that due to the pharmacology of drug combination studies the conditions necessary to support the use of ANOVA to detect synergy are typically not met. Therefore, the ANOVA technique is invalid for these drug combination studies. RP CAUDLE, RM (reprint author), NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BLDG 49,ROOM 1W-26,BETHESDA,MD 20892, USA. NR 0 TC 15 Z9 15 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD DEC PY 1993 VL 55 IS 3 BP 313 EP 317 DI 10.1016/0304-3959(93)90006-B PG 5 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA ML425 UT WOS:A1993ML42500006 PM 8121692 ER PT J AU DIEFFENBACH, CW LOWE, TMJ DVEKSLER, GS AF DIEFFENBACH, CW LOWE, TMJ DVEKSLER, GS TI GENERAL CONCEPTS FOR PCR PRIMER DESIGN SO PCR-METHODS AND APPLICATIONS LA English DT Article ID POLYMERASE CHAIN-REACTION; IMMUNODEFICIENCY-VIRUS TYPE-1; COMPUTER-PROGRAM; ANNEALING TEMPERATURE; DUPLEX STABILITY; DNA-SEQUENCES; AMPLIFICATION; RNA; OLIGONUCLEOTIDES; SPECIFICITY C1 WASHINGTON UNIV,DEPT MOLEC BIOL,ST LOUIS,MO 63110. UNIFORMED SERV UNIV HLTH SCI,DEPT PATHOL,BETHESDA,MD 20814. RP DIEFFENBACH, CW (reprint author), NIAID,DIV AIDS,BETHESDA,MD 20892, USA. NR 32 TC 95 Z9 99 U1 4 U2 44 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1054-9803 J9 PCR METH APPL JI PCR-Methods Appl. PD DEC PY 1993 VL 3 IS 3 BP S30 EP S37 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA MM596 UT WOS:A1993MM59600017 PM 8118394 ER PT J AU PIZZO, PA AF PIZZO, PA TI ZIDOVUDINE DOSAGE - REPLY SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Letter DE ZIDOVUDINE; HUMAN IMMUNODEFICIENCY VIRUS RP PIZZO, PA (reprint author), NCI,INFECT DIS SECT,PEDIAT BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD DEC PY 1993 VL 12 IS 12 BP 1038 EP 1038 DI 10.1097/00006454-199312000-00023 PG 1 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA ML420 UT WOS:A1993ML42000023 ER PT J AU CUBELLI, R NICHELLI, P PENTORE, R AF CUBELLI, R NICHELLI, P PENTORE, R TI ANARTHRIA IMPAIRS SUBVOCAL COUNTING SO PERCEPTUAL AND MOTOR SKILLS LA English DT Article ID SHORT-TERM-MEMORY; SPEECH; ARTICULATION AB We studied subvocal counting in two pure anarthric patients. Analysis showed that they performed definitively worse than normal subjects free to articulate subvocally and their scores were in the lower bounds of the performances of subjects suppressing articulation. These results suggest that subvocal counting is impaired after anarthria. C1 UNIV MODENA,NEUROL CLIN,VIA POZZO 71,I-41100 MODENA,ITALY. NINCDS,MED NEUROL BRANCH,COGNIT NEUROSCI SECT,BETHESDA,MD 20892. OSPED MAGGIORE BOLOGNA,SRRF,BOLOGNA,ITALY. RI Nichelli, Paolo/F-7336-2015 OI Nichelli, Paolo/0000-0001-9756-6796 NR 14 TC 4 Z9 4 U1 0 U2 0 PU PERCEPTUAL MOTOR SKILLS PI MISSOULA PA PO BOX 9229, MISSOULA, MT 59807 SN 0031-5125 J9 PERCEPT MOTOR SKILL JI Percept. Mot. Skills PD DEC PY 1993 VL 77 IS 3 BP 971 EP 978 PN 1 PG 8 WC Psychology, Experimental SC Psychology GA MJ751 UT WOS:A1993MJ75100049 PM 8284184 ER PT J AU VASILIOU, V REUTER, SF KOZAK, CA NEBERT, DW AF VASILIOU, V REUTER, SF KOZAK, CA NEBERT, DW TI MOUSE DIOXIN-INDUCIBLE CYTOSOLIC ALDEHYDE DEHYDROGENASE-3 - AHD4 CDNA SEQUENCE, GENETIC-MAPPING, AND DIFFERENCES IN MESSENGERRNA LEVELS SO PHARMACOGENETICS LA English DT Article ID MOLECULAR-CLONING; ALBINO DELETIONS; OXIDATIVE STRESS; LIVER CYTOSOL; EXPRESSION; RAT; IDENTIFICATION; ACID; CHROMOSOME-11; EUKARYOTES AB We have cloned and sequenced the murine AHD4 cDNA encoding the 'Class 3' cytosolic aldehyde dehydrogenase (ALDH-3c). The cDNA is 1722 bp in length, excluding the poly(A+) tail, and has 5' and 3' nontranslated regions of 174 bp and 186 bp, respectively. AHD4 encodes a protein of 453 amino acids, including the first methionine (M(r) = 50 466). The murine AHD4 protein is 91% and 80% similar to the rat and human ALDH3c proteins, respectively, 64% identical to the rat microsomal ALDH 3 protein, and < 28% similar to ALDH 'Class 1' and 'Class 2' proteins. Surprisingly, in contrast to the rat gene that is expressed in both cell cultures and the intact liver, the murine Ahd-4 gene is inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin) or benzo[a]pyrene in cell cultures but not in liver of the intact adult or newborn mouse. Southern hybridization analysis of mouse DNA probed with the full-length cDNA reveals that the Ahd-4 gene is likely to span less than a total of 15 kb, and was mapped to chromosome (Chr) 11 between the Mgat-1 and Shbg loci by analysis of two multilocus crosses. AHD4 mRNA levels are strikingly elevated in the untreated mouse hepatoma Hepa-1c1c7 mutant line c37 lacking CYP1A1 (aryl hydrocarbon hydroxylase) activity and in the untreated 14CoS/14CoS mouse cell line having a homozygous deletion of about 1.2 cM on Chr 7. Our data suggest that the Ahd-4 gene in murine cell cultures is regulated by three distinct mechanisms: Ah receptor-mediated induction by TCDD or benzo[a]pyrene, CYP1A] metabolism-dependent repression, and Chr 7-mediated putative derepression. C1 UNIV CINCINNATI,MED CTR,DEPT ENVIRONM HLTH,CINCINNATI,OH 45267. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU NIA NIH HHS [R01 AG09235]; NIEHS NIH HHS [P30 ES06096] NR 47 TC 40 Z9 41 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD DEC PY 1993 VL 3 IS 6 BP 281 EP 290 DI 10.1097/00008571-199312000-00002 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA MU436 UT WOS:A1993MU43600002 PM 8148869 ER PT J AU GELBOIN, HV AF GELBOIN, HV TI CYTOCHROME-P450 AND MONOCLONAL-ANTIBODIES SO PHARMACOLOGICAL REVIEWS LA English DT Review ID RAT-LIVER CYTOCHROME-P-450; 7-ETHOXYRESORUFIN O-DEETHYLASE; ARYL-HYDROCARBON HYDROXYLASE; LYMPHOBLASTOID CELL-LINE; TERMINAL SEQUENCE-ANALYSIS; DIRECTED IMMUNOPURIFICATION; INDUCIBLE CYTOCHROME-P-450; MUTAGEN ACTIVATION; ENZYME-ACTIVITY; RABBIT LIVER RP GELBOIN, HV (reprint author), NCI,MOLEC CARCINOGENESIS LAB,BLDG 37,ROOM 3E24,BETHESDA,MD 20892, USA. NR 130 TC 72 Z9 72 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-6997 J9 PHARMACOL REV JI Pharmacol. Rev. PD DEC PY 1993 VL 45 IS 4 BP 413 EP 453 PG 41 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MP560 UT WOS:A1993MP56000002 PM 8127919 ER PT J AU CRAWLEY, JN CORWIN, RL ROBINSON, JK FELDER, CC DEVANE, WA AXELROD, J AF CRAWLEY, JN CORWIN, RL ROBINSON, JK FELDER, CC DEVANE, WA AXELROD, J TI ANANDAMIDE, AN ENDOGENOUS LIGAND OF THE CANNABINOID RECEPTOR, INDUCES HYPOMOTILITY AND HYPOTHERMIA IN-VIVO IN RODENTS SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Note DE MARIJUANA; CANNABIS; RECEPTOR; RODENT; BEHAVIOR; SEDATION; ANXIETY; FEEDING; BODY TEMPERATURE; MEMORY ID PHARMACOLOGICAL EVALUATION; ANXIOLYTIC ACTIVITY; RAT-BRAIN; DELTA-9-TETRAHYDROCANNABINOL; ANTAGONISTS; ANALOGS; BENZODIAZEPINES; DISCRIMINATION; LOCALIZATION; MARIHUANA AB Anandamide (arachidonylethanolamide), an arachidonic acid derivative isolated from the porcine brain, displays binding characteristics indicative of an endogenous ligand for the cannabinoid receptor. The functional activity of anandamide was tested in vivo using behavioral and physiological paradigms in laboratory rodents. At IP doses from 2 to 20 mg/kg in mice, anandamide significantly decreased spontaneous motor activity in a Digiscan open field. Rectal body temperature significantly decreased at doses of 10 and 20 mg/kg in rats. At doses from 0.03 to 30 mg/kg, anandamide had no significant effect on chow consumption in ad lib fed rats. Over the dose range of 2-20 mg/kg, anandamide did not show anxiolytic properties in the mouse light half arrow right over half arrow left dark exploration model of anxiety. Over the dose range of 0.3-3 mg/kg, anandamide had no effect on choice accuracy or session duration in the delayed nonmatching to sample memory task (DNMTS) in rats. These results demonstrate that anandamide has biological and behavioral effects in awake rodents, some of which are similar to the reported actions of THC. C1 NIMH,EXPTL THERAPEUT BRANCH,BEHAV NEUROPHARMACOL SECT,BETHESDA,MD 20892. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NR 47 TC 191 Z9 194 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD DEC PY 1993 VL 46 IS 4 BP 967 EP 972 DI 10.1016/0091-3057(93)90230-Q PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA MJ760 UT WOS:A1993MJ76000034 PM 7906042 ER PT J AU FRENCH, D WITKIN, JM AF FRENCH, D WITKIN, JM TI EFFECTS OF THE DOPAMINE RELEASE INHIBITOR, CGS-10746B, ON THE LOCOMOTOR STIMULANT AND DISCRIMINATIVE STIMULUS EFFECTS OF COCAINE AND METHAMPHETAMINE SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Note DE CGS-10746B; COCAINE; METHAMPHETAMINE; LOCOMOTOR ACTIVITY; DISCRIMINATIVE STIMULUS EFFECTS; MICE; RATS ID FREELY MOVING RATS; D-AMPHETAMINE; ANTAGONISM; MOUSE; DRUGS; ABUSE AB CGS 10746B or 5-(4-methyl-1 piperazinyl)-imadazo[2,1-b]1,3,5]benzothiadiazepine maleate is a clozapine analog that, unlike clozapine, produces decreases in neostriatal dopamine release without changing dopamine metabolism or occupying D2 receptors. CGS 10746B also blocks neuronal impulse flow. The ability of this atypical antipsychotic candidate to alter the discriminative stimulus effects induced by cocaine or methamphetamine in rats or the stimulation of locomotor activity in mice was evaluated. A range of doses of CGS 10746B was tested against maximally effective doses of the psychomotor stimulants. Although CGS 10746B completely blocked the locomotor stimulant effects of cocaine and methamphetamine, it also decreased spontaneous activity in mice over the same dose range. Rats were trained to discriminate 10 mg/kg cocaine or 1 mg/kg methamphetamine from saline. The discriminative stimulus effects of cocaine or methamphetamine were not blocked by CGS 10746B. Thus, in contrast to other potential atypical antipsychotic compounds (e.g., D1 receptor antagonists), CGS 10746B does not appear to produce selective blockade of these behavioral effects of psychomotor stimulant compounds. C1 NIDA,ADDICT RES CTR,PSYCHOBIOL SECT,DRUG DEV GRP,POB 5180,BALTIMORE,MD 21224. NR 28 TC 15 Z9 15 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD DEC PY 1993 VL 46 IS 4 BP 989 EP 993 DI 10.1016/0091-3057(93)90233-J PG 5 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA MJ760 UT WOS:A1993MJ76000037 PM 8309980 ER PT J AU BJELOGRLIC, N PENG, RX PARK, SS GELBOIN, HV HONKAKOSKI, P PELKONEN, O VAHAKANGAS, K AF BJELOGRLIC, N PENG, RX PARK, SS GELBOIN, HV HONKAKOSKI, P PELKONEN, O VAHAKANGAS, K TI INVOLVEMENT OF P450 1A1 IN BENZO(A)PYRENE BUT NOT IN BENZO(A)PYRENE-7,8-DIHYDRODIOL ACTIVATION BY 3-METHYLCHOLANTHRENE-INDUCED MOUSE-LIVER MICROSOMES SO PHARMACOLOGY & TOXICOLOGY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; MONOCLONAL-ANTIBODIES; DNA ADDUCTS; BENZOPYRENE METABOLITES; RECOMMENDED NOMENCLATURE; GLUTATHIONE CONJUGATION; CYTOCHROME-P-450; RAT; BINDING; INVITRO AB Synchronous fluorescence spetrophotometry for benzo(a)pyrene-7,8-diol-9,10-epoxide (BPDE)-DNA adducts was used to study the activation pathway of benzo(a)pyrene in C57BL/6 mice. Benzo(a)pyrene but not benzo(a)pyrene-7, 8-diol activation by 3-methylcholanthrene-induced mouse liver microsomes was inhibited by a monoclonal antibody (Mab 1-7-1) against CYP1A1/2 suggesting that 1A1 probably takes part in the first P450 reaction. However, aryl hydrocarbon hydroxylase activity, a classical measure of benzo(a)pyrene metabolism, was not inhibited by the same concentration of Mab 1-7-1. None of the other antibodies used, detecting 2A, 2B, 2C or 2E subfamilies, inhibited the adduct formation. Troleandomycin and gestodene, chemical inhibitors of human 3A4, inhibited benzo(a)pyrene-7,8-diol activation by 3-methylcholanthrene-induced microsomes to some extent only in high concentrations. Although liver microsomes from 3-methylcholanthrene-induced mice catalyzed the formation of BPDE-DNA in vitro clearly more than uninduced microsomes, 3-methylcholanthrene pretreatment in vivo decreased the adduct formation in benzo(a)pyrene-treated mice. These results emphasize the significance of detoxicating and DNA-repairing pathways in vivo. Finally, synchronous fluorescence spectrophotometry for BPDE-DNA measures the end-point of the three-step activation pathway while aryl hydrocarbon hydroxylase measures a one-step hydroxylation. Thus, these methods should be used rather as corroborative than mutually exclusive assays. C1 NCI,BETHESDA,MD 20892. UNIV KUOPIO,DEPT PHARMACOL & TOXICOL,SF-70211 KUOPIO,FINLAND. RP BJELOGRLIC, N (reprint author), UNIV OULU,DEPT PHARMACOL & TOXICOL,SF-90220 OULU,FINLAND. OI Honkakoski, Paavo/0000-0002-4332-3577 NR 43 TC 6 Z9 6 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0901-9928 J9 PHARMACOL TOXICOL JI Pharmacol. Toxicol. PD DEC PY 1993 VL 73 IS 6 BP 319 EP 324 PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA MT095 UT WOS:A1993MT09500007 PM 8153055 ER PT J AU BOWLBY, NR ESPE, M BHATNAGAR, R WANG, J HOGANSON, C MCINTOSH, L BABCOCK, GT AF BOWLBY, NR ESPE, M BHATNAGAR, R WANG, J HOGANSON, C MCINTOSH, L BABCOCK, GT TI ANALYTICAL PROCEDURES FOR THE QUANTIFICATION OF ISOTOPIC AMINO-ACID-INCORPORATION INTO PHOTOSYNTHETIC PROTEINS OF SYNECHOCYSTIS PCC-6803 SO PHOTOSYNTHESIS RESEARCH LA English DT Article DE AUXOTROPH; MASS SPECTROMETRY; PHOTOSYSTEM II; TYROSINE ID PHOTOSYSTEM-II; TYROSINE RADICALS; SPECTROSCOPY AB The mechanism of oxygen evolution has been an enigma for nearly two centuries. Pioneering work by Bessel Kok, Pierre Joliot, and many others during the last quarter century has provided valuable insight into this most unique and important chemical reaction. The late 1970s and early 1980s saw the introduction of biochemical techniques for the purification of photosynthetic complexes that have, in turn, stimulated the biophysical chemists and spectroscopists to apply high resolution techniques in order to resolve the structure/function relationships in these protein complexes. Valuable information about events at the atomic level can be gained through isotopic substitution of particular amino acids thought to be important in the catalytic process. The ability to generate functional auxotrophs in the photosynthetic cyanobacterium Synechocystis 6803 has been used successfully to identify the redox active components Z and D as tyrosine residues in the reaction center of Photosystem II. In this report, we present results of the application of specific isotopic labeling for high resolution spectroscopy of purified PS II particles. We have developed analytical procedures for monitoring the incorporation of both H-2 and O-17 labeled amino acids by gas chromatography-mass spectroscopic analysis. We also show that the growth curve of cells subjected to obligate auxotrophy displays two distinct stationary phases; one that corresponds to depletion of exogenous amino acids, and a second that corresponds to the normal cell density at stationary phase. Cells harvested at the second stationary phase show little or no retention of the labeled amino acid. C1 MICHIGAN STATE UNIV,DEPT CHEM,E LANSING,MI 48824. MICHIGAN STATE UNIV,DOE,PLANT RES LAB,E LANSING,MI 48824. MICHIGAN STATE UNIV,DEPT BIOCHEM,E LANSING,MI 48824. MICHIGAN STATE UNIV,NIH,MASS SPECTROMETRY FACIL,E LANSING,MI 48824. NR 11 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0166-8595 J9 PHOTOSYNTH RES JI Photosynth. Res. PD DEC PY 1993 VL 38 IS 3 BP 379 EP 386 DI 10.1007/BF00046764 PG 8 WC Plant Sciences SC Plant Sciences GA MX417 UT WOS:A1993MX41700019 PM 24317993 ER PT J AU GOLOMB, D RINZEL, J AF GOLOMB, D RINZEL, J TI DYNAMICS OF GLOBALLY COUPLED INHIBITORY NEURONS WITH HETEROGENEITY SO PHYSICAL REVIEW E LA English DT Article ID INTERACTING OSCILLATORS; PHASE-TRANSITION; POPULATIONS; BEHAVIOR; SYSTEMS; MODEL AB A model of many heterogeneous excitable neurons with a global slowly decaying inhibitory coupling is studied. When neuronal intrinsic excitability parameters are randomly distributed, the system exhibits four regimes of behavior. In addition to synchronized periodic and asynchronous regimes, we obtain two aperiodic regimes, with bursting rate a staircaselike function of neuron excitability. In one regime, the system is partially synchronized and, in the second, partially antisynchronized. The transition between these two regimes is discontinuous as the disorder increases. RP GOLOMB, D (reprint author), NIDDKD,MATH RES BRANCH,BLDG 31,ROOM 4B-54,BETHESDA,MD 20892, USA. NR 25 TC 105 Z9 106 U1 0 U2 9 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1063-651X J9 PHYS REV E JI Phys. Rev. E PD DEC PY 1993 VL 48 IS 6 BP 4810 EP 4814 DI 10.1103/PhysRevE.48.4810 PG 5 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA MQ164 UT WOS:A1993MQ16400081 ER PT J AU CIUFFO, GM HEEMSKERK, FMJ SAAVEDRA, JM AF CIUFFO, GM HEEMSKERK, FMJ SAAVEDRA, JM TI PURIFICATION AND CHARACTERIZATION OF ANGIOTENSIN-II AT(2)-RECEPTORS FROM NEONATAL RAT-KIDNEY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CGP42112; AFFINITY CHROMATOGRAPHY; CROSS-LINKING ID RECEPTOR SUBTYPES; BINDING PROTEIN; BRAIN; AFFINITY; LIVER; MECHANISMS; EXPRESSION; CELLS; SITES AB Angiotensin II (Ang II) AT2 receptors were purified 40,000-fold to a nearly homogeneous state after solubilization from neonatal rat kidney membranes with 3-[(3-cholamidopropyl)dimethylammonio]-2-hydroxy-1-propane-sulfonic acid. Comparable IC50 values for the soluble extract (0.32 nM) and membranes (0.31 nM) were obtained by competition curves with I-125-labeled CGP42112, a selective AT2 ligand. Binding to AT2 receptors in the soluble extract was not sensitive to dithiothreitol. AT2 receptors were further purified by gel filtration and a CGP42112 Sepharose affinity column. Ang II AT2 receptors were selectively eluted with 5 muM CGP42112 at 4-degrees-C, and a single band with an apparent molecular mass of 71 kDa was obtained after SDS/PAGE. Two-dimensional electrophoresis confirmed the purity of the protein and an isoelectric point of 5.3-5.5 was obtained. A highly selective elution of the AT2 receptors from the affinity column was performed with 5 nM I-125-labeled CGP42112 at room temperature after the column was treated with 1 muM losartan in the presence of high salt. After cross-linking, a major labeled protein with similar molecular mass and isoelectric point was obtained. Dissociation of the radiolabeled protein was insensitive to losartan but was enhanced by CGP42112, PD123177, Ang II, and [Sar1]Ang II. In summary, Ang II AT2 receptors were purified by CGP42112 affinity chromatography and selective elution and retain the pharmacological specificity of particulate receptors. RP CIUFFO, GM (reprint author), NIMH,CLIN SCI LAB,PHARMACOL SECT,BLDG 10,ROOM 2D-45,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 37 TC 13 Z9 13 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 DEC 1 PY 1993 VL 90 IS 23 BP 11009 EP 11013 DI 10.1073/pnas.90.23.11009 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MK094 UT WOS:A1993MK09400027 PM 8248203 ER PT J AU WIKENHEISER, KA VORBROKER, DK RICE, WR CLARK, JC BACHURSKI, CJ OIE, HK WHITSETT, JA AF WIKENHEISER, KA VORBROKER, DK RICE, WR CLARK, JC BACHURSKI, CJ OIE, HK WHITSETT, JA TI PRODUCTION OF IMMORTALIZED DISTAL RESPIRATORY EPITHELIAL-CELL LINES FROM SURFACTANT PROTEIN-C SIMIAN VIRUS-40 LARGE TUMOR-ANTIGEN TRANSGENIC MICE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID II CELLS; PHOSPHOLIPID SECRETION; MESSENGER-RNA; LUNG; GENE; EXPRESSION; SEQUENCE; GROWTH; CULTURE; INVITRO AB Murine lung epithelial (MLE) cell lines representing the distal bronchiolar and alveolar epithelium were produced from lung tumors generated in transgenic mice harboring the viral oncogene simian virus 40 (SV40) large tumor antigen under transcriptional control of a promoter region from the human surfactant protein C (SP-C) gene. The cell lines exhibited rapid growth, lack of contact inhibition, and an epithelial cell morphology for 30-40 passages in culture. Microvilli, cytoplasmic multivesicular bodies, and multilamellar inclusion bodies (morphologic characteristics of alveolar type II cells) were detected in some of the MLE cell lines by electron microscopic analysis. The MLE cells also maintained functional characteristics of distal respiratory epithelial cells including the expression of surfactant proteins and mRNAs and the ability to secrete phospholipids. Expression of the exogenous SV40 large tumor antigen gene was detected in all of the generated cell lines. The SP-C/SV40 large tumor antigen transgenic mice and the MLE cell lines will be useful for the study of pulmonary surfactant production and regulation as well as lung development and tumorigenesis. C1 USN HOSP,NCI,NAVAL MED ONCOL BRANCH,BETHESDA,MD 20814. RP WIKENHEISER, KA (reprint author), CHILDRENS HOSP MED CTR,DIV PULM BIOL,CINCINNATI,OH 45229, USA. FU NHLBI NIH HHS [HL38764, HL28623, HL41496] NR 35 TC 256 Z9 260 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 DEC 1 PY 1993 VL 90 IS 23 BP 11029 EP 11033 DI 10.1073/pnas.90.23.11029 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MK094 UT WOS:A1993MK09400031 PM 8248207 ER PT J AU LUBAHN, DB MOYER, JS GOLDING, TS COUSE, JF KORACH, KS SMITHIES, O AF LUBAHN, DB MOYER, JS GOLDING, TS COUSE, JF KORACH, KS SMITHIES, O TI ALTERATION OF REPRODUCTIVE FUNCTION BUT NOT PRENATAL SEXUAL DEVELOPMENT AFTER INSERTIONAL DISRUPTION OF THE MOUSE ESTROGEN-RECEPTOR GENE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HOMOLOGOUS RECOMBINATION; GENE TARGETING; FERTILITY ID MESSENGER-RNA; BREAST-CANCER; STEM-CELLS; EXPRESSION; MUTATION; EMBRYOS; REGION AB Estrogen receptor and its ligand, estradiol, have long been thought to be essential for survival, fertility, and female sexual differentiation and development. Consistent with this proposed crucial role, no human estrogen receptor gene mutations are known, unlike the androgen receptor, where many loss of function mutations have been found. We have generated mutant mice lacking responsiveness to estradiol by disrupting the estrogen receptor gene by gene targeting. Both male and female animals survive to adulthood with normal gross external phenotypes. Females are infertile; males have a decreased fertility. Females have hypoplastic uteri and hyperemic ovaries with no detectable corpora lutea. In adult wild-type and heterozygous females, 3-day estradiol treatment at 40 mug/kg stimulates a 3- to 4-fold increase in uterine wet weight and alters vaginal cornification, but the uteri and vagina do not respond in the animals with the estrogen receptor gene disruption. Prenatal male and female reproductive tract development can therefore occur in the absence of estradiol receptor-mediated responsiveness. C1 NIEHS,REPROD & DEV TOXICOL LAB,RECEPTOR BIOL SECT,POB 12233,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,DEPT PATHOL,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT PEDIAT,CHAPEL HILL,NC 27599. UNIV N CAROLINA,REPROD BIOL LABS,CHAPEL HILL,NC 27599. NIEHS,REPROD & DEV TOXICOL LAB,GAMETE BIOL SECT,RES TRIANGLE PK,NC 27709. OI Korach, Kenneth/0000-0002-7765-418X FU NIGMS NIH HHS [GM20069] NR 39 TC 1274 Z9 1297 U1 2 U2 19 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 DEC 1 PY 1993 VL 90 IS 23 BP 11162 EP 11166 DI 10.1073/pnas.90.23.11162 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MK094 UT WOS:A1993MK09400058 PM 8248223 ER PT J AU SMITH, CL ARCHER, TK HAMLINGREEN, G HAGER, GL AF SMITH, CL ARCHER, TK HAMLINGREEN, G HAGER, GL TI NEWLY EXPRESSED PROGESTERONE-RECEPTOR CANNOT ACTIVATE STABLE, REPLICATED MOUSE MAMMARY-TUMOR VIRUS TEMPLATES BUT ACQUIRES TRANSACTIVATION POTENTIAL UPON CONTINUOUS EXPRESSION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HORMONE REGULATORY ELEMENT; MMTV PROMOTER; POSITIONED NUCLEOSOMES; NUCLEAR-LOCALIZATION; CHROMATIN STRUCTURE; ESTROGEN-RECEPTOR; TRANSCRIPTION; INDUCTION; CELLS; GENE AB During development and differentiation, the expression of transcription factors is regulated in a temporal fashion. Newly expressed transcription factors must interact productively with target genes organized in chromatin. Although the mechanisms governing factor binding to chromatin templates are not well understood, it is now clear that template access can be dramatically influenced by nucleoprotein structure. We have examined the ability of a well characterized transactivator, the progesterone receptor (PR), to activate the mouse mammary tumor virus (MMTV) promoter organized either in stable, replicating templates that have a highly ordered nucleosome structure or as transiently transfected DNA, which adopts a less-defined structure. If the PR is transiently expressed in cells harboring both replicated and transient MMTV reporter constructs, it cannot significantly activate the stable replicated MMTV template. In contrast, when PR cDNA is stably inserted into the same cells and constitutively expressed, it gains the ability to activate both chromosomal and transiently introduced templates. These results demonstrate that newly expressed PR is not competent to activate the MMTV template in its native nucleoprotein conformation but acquires this ability upon prolonged expression in replicating cells. C1 NCI,MOLEC VIROL LAB,HORMONE ACT & ONCOGENESIS SECT,BETHESDA,MD 20892. NCI,FREDERICK CANC RES DEV CTR,PRI DYNCORP,AIDS FLOW CYTOMETRY LAB,FREDERICK,MD 21701. FU NCI NIH HHS [N01-CO-74102] NR 35 TC 43 Z9 43 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 1 PY 1993 VL 90 IS 23 BP 11202 EP 11206 DI 10.1073/pnas.90.23.11202 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MK094 UT WOS:A1993MK09400066 PM 8248228 ER PT J AU WANG, N GOTTESMAN, S WILLINGHAM, MC GOTTESMAN, MM MAURIZI, MR AF WANG, N GOTTESMAN, S WILLINGHAM, MC GOTTESMAN, MM MAURIZI, MR TI A HUMAN MITOCHONDRIAL ATP-DEPENDENT PROTEASE THAT IS HIGHLY HOMOLOGOUS TO BACTERIAL LON PROTEASE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PROTEASE LA; MITOCHONDRIA; PROTEIN DEGRADATION ID ESCHERICHIA-COLI; LIVER-MITOCHONDRIA; GENE-PRODUCT; ION GENE; LA; PROTEINS; DEGRADATION; SEQUENCE; PEPTIDES; PROTEOLYSIS AB We have cloned a human ATP-dependent protease that is highly homologous to members of the bacterial Lon protease family. The cloned gene encodes a protein of 963 amino acids with a calculated molecular mass of 106 kDa, slightly higher than that observed by Western blotting the protein from human tissues and cell lines (100 kDa). A single species of mRNA was found for this Lon protease in all human tissues examined. The protease is encoded in the nucleus, and the amino-terminal portion of the protein sequence contains a potential mitochondrial targeting presequence. Immunofluorescence microscopy suggested a predominantly mitochondrial localization for the Lon protease in cultured human cells. A truncated LON gene, in which translation was initiated at Met118 of the coding sequence, was expressed in Escherichia coli and produced a protease that degraded alpha-casein in vitro in an ATP-dependent manner and had other properties similar to E. coli Lon protease. C1 NCI,CELL BIOL LAB,BLDG 37,ROOM 1B22,BETHESDA,MD 20892. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. MED UNIV S CAROLINA,DEPT PATHOL & LAB MED,DIV ANAT PATHOL,CHARLESTON,SC 29425. NR 43 TC 158 Z9 165 U1 1 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 DEC 1 PY 1993 VL 90 IS 23 BP 11247 EP 11251 DI 10.1073/pnas.90.23.11247 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MK094 UT WOS:A1993MK09400075 PM 8248235 ER PT J AU BEARER, EL DEGIORGIS, JA BODNER, RA KAO, AW REESE, TS AF BEARER, EL DEGIORGIS, JA BODNER, RA KAO, AW REESE, TS TI EVIDENCE FOR MYOSIN MOTORS ON ORGANELLES IN SQUID AXOPLASM SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FAST AXONAL-TRANSPORT; ACTIN-FILAMENTS; QUANTITATIVE ASSAY; SOLUBLE FACTORS; GIANT-AXON; MOVEMENT; KINESIN; INVITRO; GENE; ACANTHAMOEBA AB Squid axoplasm has proved a rich source for the identification of motors involved in organelle transport. Recently, squid axoplasmic organelles have been shown to move on invisible tracks that are sensitive to cytochalasin, suggesting that these tracks are actin filaments. Here, an assay is described that permits observation of organelles moving on unipolar actin bundles. This assay is used to demonstrate that axoplasmic organelles move on actin filaments in the barbed-end direction, suggesting the presence of a myosin motor on axoplasmic organelles. Indeed, axoplasm contains actin-dependent ATPase activity, and a pan-myosin antibody recognized at least four bands in Western blots of axoplasm. An almost-equal-to 235-kDa band copurified in sucrose gradients with KI-extracted axoplasmic organelles, and the myosin antibody stained the organelle surfaces by immunogold electron microscopy. The myosin is present on the surface of at least some axoplasmic organelles and thus may be involved in their transport through the axoplasm, their movement through the cortical actin in the synapse, or some other aspect of axonal function. C1 NIH, NEUROBIOL LAB, BETHESDA, MD 20892 USA. MARINE BIOL LAB, WOODS HOLE, MA 02543 USA. RP BROWN UNIV, DIV BIOL & MED, PROVIDENCE, RI 02912 USA. NR 36 TC 72 Z9 72 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 1 PY 1993 VL 90 IS 23 BP 11252 EP 11256 DI 10.1073/pnas.90.23.11252 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MK094 UT WOS:A1993MK09400076 PM 8248236 ER PT J AU BARTFAI, T LANGEL, U BEDECS, K ANDELL, S LAND, T GREGERSEN, S AHREN, B GIROTTI, P CONSOLO, S CORWIN, R CRAWLEY, J XU, XJ WIESENFELDHALLIN, Z HOKFELT, T AF BARTFAI, T LANGEL, U BEDECS, K ANDELL, S LAND, T GREGERSEN, S AHREN, B GIROTTI, P CONSOLO, S CORWIN, R CRAWLEY, J XU, XJ WIESENFELDHALLIN, Z HOKFELT, T TI GALANIN-RECEPTOR LIGAND M40 PEPTIDE DISTINGUISHES BETWEEN PUTATIVE GALANIN-RECEPTOR SUBTYPES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PEPTIDE ANTAGONIST; ACETYLCHOLINE RELEASE; NOCICEPTIVE REFLEX; FEEDING; INSULIN ID RAT VENTRAL HIPPOCAMPUS; BINDING-SITES; MOLECULAR CHARACTERIZATION; PHOSPHOINOSITIDE TURNOVER; ACETYLCHOLINE-RELEASE; CHIMERIC PEPTIDE; NEURONS; STIMULATION; BLOCKS; INHIBITION AB The galanin-receptor ligand M40 [galanin-(1-12)-Pro3-(Ala-Leu)2-Ala amide] binds with high affinity to [mono[I-125]iodo-Tyr26]galanin-binding sites in hippocampal, hypothalamic, and spinal cord membranes and in membranes from Rin m5F rat insulinoma cells (IC50 = 3-15 nM). Receptor autoradiographic studies show that M40 (1 muM) displaces [mono[I-125]iodo-Tyr26]galanin from binding sites in the hippocampus, hypothalamus, and spinal cord. In the brain, M40 acts as a potent galanin-receptor antagonist: M40, in doses comparable to that of galanin, antagonizes the stimulatory effects of galanin on feeding, and it blocks the galaninergic inhibition of the scopolamine-induced acetylcholine release in the ventral hippocampus in vivo. In contrast, M40 completely fails to antagonize both the galanin-mediated inhibition of the glucose-induced insulin release in isolated mouse pancreatic islets and the inhibitory effects of galanin on the forskolin-stimulated accumulation of 3',5'-cAMP in Rin m5F cells; instead M40 is a weak agonist at the galanin receptors in these two systems. M40 acts as a weak antagonist of galanin in the spinal flexor reflex model. These results suggest that at least two subtypes of the galanin receptor may exist. Hypothalamic and hippocampal galanin receptors represent a putative central galanin-receptor subtype (GL-1-receptor) that is blocked by M40. The pancreatic galanin receptor may represent another subtype (GL-2-receptor) that recognizes M40, but as a weak agonist. The galanin receptors in the spinal cord occupy an intermediate position between these two putative subtypes. C1 LUND UNIV,MALMO GEN HOSP,DEPT MED,S-21401 MALMO,SWEDEN. MARIO NEGRI INST PHARMACOL RES,I-20157 MILAN,ITALY. NATL INST MENTAL HLTH-CC64M,BEHAV NEUROPHARMACOL SECT,BETHESDA,MD 20892. KAROLINSKA INST,CLIN NEUROPHYSIOL SECT,S-14186 HUDDINGE,SWEDEN. KAROLINSKA INST,DEPT NEUROSCI,S-10401 STOCKHOLM 60,SWEDEN. RP BARTFAI, T (reprint author), UNIV STOCKHOLM,ARRHENIUS LAB,DEPT NEUROCHEM & NEUROTOXICOL,S-10691 STOCKHOLM,SWEDEN. FU NIA NIH HHS [AG 10441-03] NR 36 TC 131 Z9 134 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 1 PY 1993 VL 90 IS 23 BP 11287 EP 11291 DI 10.1073/pnas.90.23.11287 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MK094 UT WOS:A1993MK09400083 PM 7504301 ER PT J AU THORGEIRSSON, SS EVARTS, RP BISGAARD, HC FUJIO, K HU, ZY AF THORGEIRSSON, SS EVARTS, RP BISGAARD, HC FUJIO, K HU, ZY TI HEPATIC STEM-CELL COMPARTMENT - ACTIVATION AND LINEAGE COMMITMENT SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article; Proceedings Paper CT SEBM Symposium/FASEB Meeting in Search of a Hepatic Stem Cell CY MAR 29, 1993 CL NEW ORLEANS, LA SP SOC EXPTL BIOL & MED, FEDERAT AMER SOC EXPTL BIOL ID LIVER EPITHELIAL-CELLS; GROWTH-FACTOR-ALPHA; RAT-LIVER; OVAL CELLS; NEOPLASTIC TRANSFORMATION; POLYCHLORINATED-BIPHENYLS; REGENERATING LIVER; EXPRESSION; DIFFERENTIATION; PROLIFERATION RP THORGEIRSSON, SS (reprint author), NCI,DIV CANC ETIOL,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 40 TC 91 Z9 91 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD DEC PY 1993 VL 204 IS 3 BP 253 EP 260 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PC073 UT WOS:A1993PC07300003 PM 7694304 ER PT J AU WALSH, CE LIU, JM MILLER, JL NIENHUIS, AW SAMULSKI, RJ AF WALSH, CE LIU, JM MILLER, JL NIENHUIS, AW SAMULSKI, RJ TI GENE-THERAPY FOR HUMAN HEMOGLOBINOPATHIES SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID ADENO-ASSOCIATED VIRUS; BETA-GLOBIN GENE; DOMINANT CONTROL REGION; HEMATOPOIETIC STEM-CELLS; LOCUS-CONTROL REGION; HUMAN GAMMA-GLOBIN; MURINE ERYTHROLEUKEMIA-CELLS; RETROVIRAL-MEDIATED TRANSFER; BONE-MARROW TRANSPLANTATION; HIGH-LEVEL EXPRESSION C1 UNIV PITTSBURGH,DEPT BIOL SCI,PITTSBURGH,PA 15260. NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. NR 87 TC 29 Z9 29 U1 0 U2 7 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD DEC PY 1993 VL 204 IS 3 BP 289 EP 300 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PC073 UT WOS:A1993PC07300007 PM 8234372 ER PT J AU SAFAR, J ROLLER, PP GAJDUSEK, DC GIBBS, CJ AF SAFAR, J ROLLER, PP GAJDUSEK, DC GIBBS, CJ TI THERMAL-STABILITY AND CONFORMATIONAL TRANSITIONS OF SCRAPIE AMYLOID (PRION) PROTEIN CORRELATE WITH INFECTIVITY SO PROTEIN SCIENCE LA English DT Article DE CONFORMATION; INFECTIVITY; PRION PROTEIN; SCRAPIE AMYLOID; TRANSITIONS ID CIRCULAR-DICHROISM SPECTRA; SECONDARY STRUCTURE; FORM; DECONVOLUTION; TRYPTOPHAN; PEPTIDES; HAMSTERS; DISEASE; HELICES; AGENT AB The scrapie amyloid (prion) protein (PrP27-30) is the protease-resistant core of a larger precursor (PrP(Sc)) and a component of the infectious scrapie agent; the potential to form amyloid is a result of a posttranslational event or conformational abnormality. The conformation, heat stability, and solvent-induced conformational transitions of PrP27-30 were studied in the solid state in films by CD spectroscopy and correlated with the infectivity of rehydrated and equilibrated films. The exposure of PrP27-30 in films to 60-degrees-C, 100-degrees-C, and 132-degrees-C for 30 min did not change the beta-sheet secondary structure; the infectivity slightly diminished at 132-degrees-C and correlated with a decreased solubility of PrP27-30 in sodium dodecyl sulfate (SDS), probably due to cross-linking. Exposing PrP27-30 films to formic acid (FA), trifluoroacetic acid (TFA), trifluoroethanol (TFE), hexafluoro-2-propanol (HFIP), and SDS transformed the amide CD band, diminished the mean residue ellipticity of aromatic bands, and inactivated scrapie infectivity. The convex constraint algorithm (CAA) deconvolution of the CD spectra of the solvent-exposed and rehydrated solid state PrP27-30 identified five common spectral components. The loss of infectivity quantitatively correlated with a decreasing proportion of native, beta-pleated sheet-like secondary structure component, an increasing amount of alpha-helical component, and an increasingly disordered tertiary structure. The results demonstrate the unusual thermal stability of the beta-sheet secondary structure of PrP27-30 protein in the solid state. The conformational perturbations of PrP27-30 parallel the changes in infectivity and suggest that the beta-sheet structure plays a key role in the physical stability of scrapie amyloid and in the ability to propagate and replicate scrapie. C1 NCI,DCT,DTP,MED CHEM LAB,BETHESDA,MD 20892. RP SAFAR, J (reprint author), NINCDS,CENT NERVOUS SYST STUDIES LAB,BLDG 36,ROOM 4A-15,BETHESDA,MD 20892, USA. RI Safar, Jiri/G-6512-2013 NR 42 TC 161 Z9 166 U1 2 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD DEC PY 1993 VL 2 IS 12 BP 2206 EP 2216 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MK556 UT WOS:A1993MK55600020 PM 7905316 ER PT J AU ABERGEL, C PADLAN, EA KASHMIRI, SVS MILENIC, D CALVO, B SCHLOM, J AF ABERGEL, C PADLAN, EA KASHMIRI, SVS MILENIC, D CALVO, B SCHLOM, J TI CRYSTALLOGRAPHIC STUDIES AND PRIMARY STRUCTURE OF THE ANTITUMOR MONOCLONAL CC49 FAB' SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE CRYSTALLIZATION; ANTITUMOR; ANTIBODY; PRIMARY STRUCTURE ID ANTIBODY B72.3; BINDING-PROPERTIES; ANTIGEN; GENERATION; EXPRESSION; CELLS; MOUSE AB The Fab' of CC49, a murine monoclonal antibody directed against the human tumor-associated antigen TAG-72 has been crystallized. The crystals are monoclinic, space group P2(1) with cell parameters a = 115.6 angstrom, b = 116.4 angstrom, and c = 70.3 angstrom; beta = 97.8-degrees. The size of the unit cell is compatible with four Fab' molecules in the asymmetric unit. The Fab molecules are related by two approximately perpendicular pseudo-2-fold axes. One pseudo-2-fold axis is parallel to the crystallographic 2-fold axis and was found by inspection of the Harker section of the native Patterson map; the other was found by a self rotation function. The primary structures of the variable regions of the CC49 antibody light and heavy chains have been determined and are compared with those of the related antitumor antibody B72.3. (C) 1993 Wiley-Liss, Inc.* C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. RP ABERGEL, C (reprint author), NIDDKD,MOLEC BIOL LAB,BLDG 5,ROOM 303,BETHESDA,MD 20892, USA. NR 29 TC 3 Z9 3 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-3585 J9 PROTEINS JI Proteins PD DEC PY 1993 VL 17 IS 4 BP 438 EP 443 DI 10.1002/prot.340170411 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MJ757 UT WOS:A1993MJ75700010 PM 8108385 ER PT J AU PAZZAGLIA, PJ POST, RM KETTER, TA GEORGE, MS MARANGELL, LB AF PAZZAGLIA, PJ POST, RM KETTER, TA GEORGE, MS MARANGELL, LB TI PRELIMINARY CONTROLLED TRIAL OF NIMODIPINE IN ULTRA-RAPID CYCLING AFFECTIVE DYSREGULATION SO PSYCHIATRY RESEARCH LA English DT Article DE CALCIUM CHANNEL BLOCKERS; AFFECTIVE DISORDERS; RAPID-CYCLING BIPOLAR; DISORDERS; DEPRESSION; PHARMACOTHERAPY ID INTRACELLULAR CALCIUM-CONCENTRATION; AFFECTIVE-DISORDERS; RAT-BRAIN; SUBARACHNOID HEMORRHAGE; ANTAGONIST NIMODIPINE; CHANNEL ANTAGONISTS; DEPRESSIVE-ILLNESS; LIMBIC SEIZURES; ACUTE MANIA; LITHIUM AB We report the initial results of the first controlled double-blind trial of nomodipine, a calcium channel antagonist, in the acute and prophylactic treatment of patients with treatment-refractory affective dysregulation. Active drug nimodipine (A) was substituted for placebo (B) in 12 patients. Patients were studied in a B-A-B design, with 3 of the 12 patients rechallenged with active drug in a B-A-B-A design (patients 9, 10, and 11). Five of the nine patients who completed the drug trial responded. One of three patients suffering from ultra-ultra-rapid (ultradian) cycling bipolar II disorder (patient 6) showed an essentially complete response; the other two ultradian patients (patients 4 and 9) showed evidence of a partial response on manic and depressive oscillations, one of which was confirmed in a B-A-B-A design. Only one of five less rapidly, but continuously cycling patients showed an excellent response (patient 10), and this was confirmed in a B-A-B-A design. The one patient who had recurrent brief depression (patient ii) showed a complete resolution of severe depressive recurrences, with response re-confirmed in an extended prophylactic trial with a B-A-B-A design. In the eight patients who completed self-ratings, nimodipine was associated with a significant reduction in the magnitude of mood fluctuations compared with the baseline placebo condition. Further clinical study of nimodipine, a calcium channel blocker with a unique profile of behavioral and anticonvulsant properties, appears warranted in patients with treatment-refractory affective illness characterized by recurrent brief depression and ultradian cycling. C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 81 TC 105 Z9 105 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD DEC PY 1993 VL 49 IS 3 BP 257 EP 272 DI 10.1016/0165-1781(93)90066-P PG 16 WC Psychiatry SC Psychiatry GA MT858 UT WOS:A1993MT85800006 PM 8177920 ER PT J AU NAGLER, RM BAUM, BJ FOX, PC AF NAGLER, RM BAUM, BJ FOX, PC TI EFFECTS OF X-IRRADIATION ON THE FUNCTION OF RAT SALIVARY-GLANDS AT 3 AND 40 DAYS SO RADIATION RESEARCH LA English DT Article ID PAROTID-GLAND; SECRETION; CELLS RP NAGLER, RM (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892, USA. NR 23 TC 42 Z9 44 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD DEC PY 1993 VL 136 IS 3 BP 392 EP 396 DI 10.2307/3578552 PG 5 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA MQ741 UT WOS:A1993MQ74100012 PM 8278581 ER PT J AU STONE, HB BROWN, JM PHILLIPS, TL SUTHERLAND, RM AF STONE, HB BROWN, JM PHILLIPS, TL SUTHERLAND, RM TI OXYGEN IN HUMAN TUMORS - CORRELATIONS BETWEEN METHODS OF MEASUREMENT AND RESPONSE TO THERAPY - SUMMARY OF A WORKSHOP HELD NOVEMBER 19-20, 1992, AT THE NATIONAL-CANCER-INSTITUTE, BETHESDA, MARYLAND SO RADIATION RESEARCH LA English DT Editorial Material ID INTRACAPILLARY OXYHEMOGLOBIN SATURATION; MAGNETIC-RESONANCE SPECTROSCOPY; O2 TENSION MEASUREMENTS; H-1 MR SPECTROSCOPY; INTERSTITIAL HYPERTENSION; INTRACRANIAL TUMORS; RADIATION RESPONSE; HYPOXIC FRACTION; UTERINE CERVIX; CELL-SURVIVAL C1 STANFORD UNIV,SCH MED,DEPT RADIAT ONCOL,STANFORD,CA 94305. UNIV CALIF SAN FRANCISCO,DEPT RADIAT ONCOL,SAN FRANCISCO,CA 94143. SRI INT,DIV LIFE SCI,MENLO PK,CA 94205. RP STONE, HB (reprint author), NCI,RADIOTHERAPY DEV BRANCH,EPN 800,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 49 TC 279 Z9 283 U1 0 U2 4 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD DEC PY 1993 VL 136 IS 3 BP 422 EP 434 DI 10.2307/3578556 PG 13 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA MQ741 UT WOS:A1993MQ74100016 PM 8278585 ER PT J AU MILLER, RW KOSZALKA, TR AF MILLER, RW KOSZALKA, TR TI HEMPELMANN,LOUIS,H. (1914-1993) - AN APPRECIATION SO RADIATION RESEARCH LA English DT Item About an Individual C1 ALFRED I DUPONT INST,WILMINGTON,DE 19899. RP MILLER, RW (reprint author), NCI,CLIN EPIDEMIOL BRANCH,EPN 400,BETHESDA,MD 20892, USA. NR 7 TC 3 Z9 3 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD DEC PY 1993 VL 136 IS 3 BP 435 EP 438 PG 4 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA MQ741 UT WOS:A1993MQ74100017 PM 8278586 ER PT J AU PADLAN, EA HELM, BA AF PADLAN, EA HELM, BA TI MODELING OF THE LECTIN-HOMOLOGY DOMAINS OF THE HUMAN AND MURINE LOW-AFFINITY FC-EPSILON RECEPTOR (FC-EPSILON-RII/CD23) SO RECEPTOR LA English DT Article DE HOMOLOGY MODELING; IMMUNOGLOBULIN RECEPTORS; SEQUENCE SIMILARITY; PROTEIN ENGINEERING ID EPIDERMAL LANGERHANS CELLS; IGE-BINDING FACTORS; IMMUNOGLOBULIN-E; MOLECULAR-STRUCTURE; RII CD23; PROTEIN; EXPRESSION; ANTIBODY; FEATURES; ANTIGEN AB Models of the lectin-homology domains of the human and murine low-affinity receptors for IgE (Fc epsilon RII/CD23) were built on the basis of sequence similarity with rat mannose-binding protein, the structure of which is known. The sites on Fc epsilon RII/CD23 that are possibly involved in the interaction with IgE and with another ligand, CD21/CR2, are proposed. The models may assist the design of protein engineering experiments for the study of the reactivity of these molecules. C1 UNIV SHEFFIELD,KREBS INST BIOMOLEC RES,DEPT BIOCHEM & MOLEC BIOL,SHEFFIELD S10 2UH,S YORKSHIRE,ENGLAND. RP PADLAN, EA (reprint author), NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 51 TC 8 Z9 10 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 1052-8040 J9 RECEPTOR JI Receptor PD WIN PY 1993 VL 3 IS 4 BP 325 EP 341 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MU737 UT WOS:A1993MU73700006 PM 8142907 ER PT J AU JOHNSON, WE VAUGHAN, C AF JOHNSON, WE VAUGHAN, C TI HABITAT USE OF SMALL TERRESTRIAL RODENTS IN THE COSTA-RICAN HIGHLANDS SO REVISTA DE BIOLOGIA TROPICAL LA English DT Article DE HABITAT; RODENTS; SPECIES RICHNESS; SPECIES DIVERSITY AB Small terrestrial rodents were studied in five habitats in the highlands of the Talamanca Mountain Range, Costa Rica. Species diversity, richness, and number of individuals increased from primary forest to non-forested habitats. Peromyscus nudipes was primarily a forest species and along with Scotinomys xerampelinus was found in all habitats sampled. Reithrodontomys creper was almost exclusively present in old fields and R. sumichrasti around buildings and in the cattle pasture. Rodent populations increased with the beginning of the rainy season, but the degree of fluctuation differed among species and habitats. RP JOHNSON, WE (reprint author), NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. NR 0 TC 1 Z9 1 U1 1 U2 2 PU REVISTA DE BIOLOGIA TROPICAL PI SAN JOSE PA UNIVERSIDAD DE COSTA RICA CIUDAD UNIVERSITARIA, SAN JOSE, COSTA RICA SN 0034-7744 J9 REV BIOL TROP JI Rev. Biol. Trop. PD DEC PY 1993 VL 41 IS 3A BP 521 EP 527 PG 7 WC Biology SC Life Sciences & Biomedicine - Other Topics GA PC554 UT WOS:A1993PC55400025 ER PT J AU ANSARI, AA AF ANSARI, AA TI A POSSIBLE ROLE OF THE MHC-ASSOCIATED INVARIANT CHAIN IN RHEUMATOID-ARTHRITIS SO SEMINARS IN ARTHRITIS AND RHEUMATISM LA English DT Article DE ANTIGEN PRESENTATION; MHC; CLASS-II PROTEIN; INVARIANT CHAIN; AUTOIMMUNITY; ARTHRITIS ID HLA-DR MOLECULES; IMMUNOGENIC PEPTIDES; HISTOCOMPATIBILITY ANTIGENS; IA; TRANSLATION; REPERTOIRE; INITIATION; TRANSPORT; BINDING; PROTEIN RP ANSARI, AA (reprint author), NIAMSD,GRANTS REVIEW BRANCH,BETHESDA,MD 20892, USA. NR 25 TC 4 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 0049-0172 J9 SEMIN ARTHRITIS RHEU JI Semin. Arthritis Rheum. PD DEC PY 1993 VL 23 IS 3 BP 193 EP 197 DI 10.1016/S0049-0172(05)80040-X PG 5 WC Rheumatology SC Rheumatology GA MP617 UT WOS:A1993MP61700006 PM 8122122 ER PT J AU BEAZOGLOU, T BROWN, LJ HEFFLEY, D AF BEAZOGLOU, T BROWN, LJ HEFFLEY, D TI DENTAL-CARE UTILIZATION OVER TIME SO SOCIAL SCIENCE & MEDICINE LA English DT Article; Proceedings Paper CT 2ND WORLD CONGRESS ON HEALTH ECONOMICS CY SEP 10-14, 1990 CL UNIV ZURICH, ZURICH, SWITZERLAND HO UNIV ZURICH DE DEMAND FOR DENTAL CARE; DENTAL UTILIZATION; DENTAL ECONOMICS ID SUPPLIER-INDUCEMENT; HEALTH-CARE; DEMAND; INSURANCE AB Between 1950 and 1978, per capita real dental expenditures in the U.S. grew at an average annual rate of 3.33%. Between 1978 and 1989 there was virtually no net growth in this measure of dental care utilization. This sharp curtailment of utilization growth has prompted debate about the sources of this change. Possible explanations include, among others, a reduction in dental disease due to increased exposure to fluoridation, the substitution of noncaloric sweeteners for refined sugar, preventive dentistry, improved oral health habits, an increase in the net price of dental services, and the cost-containment efforts of insurers and employers. Changes have occurred in all of these variables, but little has been done to isolate and quantify the individual effects. This decomposition is difficult, in part, because of the lack of an established model for time-series analysis of dental care utilization. A model of dental care demand, incorporating economic factors (out-of-pocket or net dental prices, per capita income, and nondental prices) as well as dietary factors (refined sugar consumption, noncaloric sweeteners, and exposure to fluoridated water), is combined with a simple model of dental care supply within an equilibrium framework. A two-stage estimation procedure is applied, using U.S. aggregate time-series data for the period 1950-89. Results show that economic and dietary factors are significantly related to changes in utilization. Net price and income elasticities of demand exhibit the expected signs and are compatible with estimates from cross-sectional studies. Decreases in cane and beet sugar consumption, facilitated by the increase in the use of noncaloric sweeteners, are associated with reductions in utilization. Fluoridation appears to be weakly but positively related to utilization. There also appears to have been a significant structural shift in demand since 1978. Overall goodness-of-fit is strong and the model accurately tracks the 1978-89 flattening of per capita real dental expenditures. Analysis of the relative contribution of each independent variable suggests that economic, dietary, and structural shift factors have contributed to this curtailment of growth. C1 NIDR,BETHESDA,MD 20892. UNIV CONNECTICUT,DEPT ECON,STORRS,CT 06269. RP BEAZOGLOU, T (reprint author), UNIV CONNECTICUT,CTR HLTH,DEPT PEDIAT DENT,FARMINGTON,CT 06032, USA. NR 25 TC 16 Z9 17 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD DEC PY 1993 VL 37 IS 12 BP 1461 EP 1472 DI 10.1016/0277-9536(93)90180-C PG 12 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA ME890 UT WOS:A1993ME89000006 PM 8303330 ER PT J AU STEYN, K ROSSOUW, JE JOOSTE, PL CHALTON, DO JORDAAN, ER JORDAAN, PCJ STEYN, M SWANEPOEL, ASP AF STEYN, K ROSSOUW, JE JOOSTE, PL CHALTON, DO JORDAAN, ER JORDAAN, PCJ STEYN, M SWANEPOEL, ASP TI THE INTERVENTION EFFECTS OF A COMMUNITY-BASED HYPERTENSION CONTROL PROGRAM IN 2 RURAL SOUTH-AFRICAN TOWNS - THE CORIS STUDY SO SOUTH AFRICAN MEDICAL JOURNAL LA English DT Article ID CORONARY HEART-DISEASE; BLOOD-PRESSURE; PROJECT; STROKE; BIAS AB The objective of the hypertension programme of the Coronary Risk Factor Study (CORIS) was to evaluate the effectiveness of the first 4 years of community-based intervention. The hypertension intervention model comprised a blood pressure station where the whole population was screened for hypertension, nondrug management was provided and hypertensives were monitored after referral to general practitioners for drug therapy. Two levels of intervention were maintained: in the high-intensity intervention town (N = 2 278) hypertensives were actively followed up, and in the low-intensity intervention town (N = 2 620) no active follow-up procedure existed. A third town acted as control (N = 2 290). In the cohort which was hypertensive at baseline, the net decreases in systolic blood pressure (mean +/- SE) after correction for changes in the control town were 0,5 +/- 2,2 mmHg (men) and 4,5 +/- 2,2 mmHg (women) in the low-intensity intervention town, and 5,6 2,3 mmHg (men) and 7,5 +/- 2,2 mmHg (women) in the high-intensity intervention town. The net decrease in diastolic blood pressure was 3,4 +/- 1,2 mmHg (men) and 4,4 +/- 1,1 mmHg (women) in the low-intensity intervention town, and 6,1 +/- 1,2 mmHg (men) and 5,9 +/- 1,1 mmHg (women) in the high-intensity intervention town. These reductions were statistically significant with one exception. The changes in the total population in the 3 communities after 4 years of intervention were similar to those found in the hypertensive cohort. Decreases in mean blood pressure were accompanied by marked increases in the proportion of hypertensives on drug treatment and the proportion under control (< 160/95 mmHg). Distribution curves of blood pressure indicated a large effect in the subgroup above the cut-off point for hypertension; however, the entire curve also shifted to the left, indicating, in addition, benefit to the whole population. An increase in the appropriate knowledge and action for hypertension control was observed in the intervention towns compared with the control town. The CORIS community-based hypertension control programme successfully reduced the risk for cardiovascular diseases in the intervention towns compared with the control town. C1 S AFRICAN MRC,INST BIOSTAT,PAROWVALLEI,SOUTH AFRICA. HUMAN SCI RES COUNCIL,INST SOCIAL DYNAM,PRETORIA,SOUTH AFRICA. NIH,WOMENS HLTH INITIAT,BETHESDA,MD. HOUSE ASSEMBLY,DEPT HLTH SERV & WELF,PRETORIA,SOUTH AFRICA. RP STEYN, K (reprint author), S AFRICAN MRC,CTR EPIDEMIOL RES SO AFRICA,NUTR DIS RES INST,PAROWVALLEI,SOUTH AFRICA. NR 25 TC 12 Z9 12 U1 0 U2 0 PU MED ASSOC S AFRICA PI JOHANNESBURG PA MED HOUSE CENTRAL SQ 7430 PINELANDS JOHANNESBURG, SOUTH AFRICA SN 0038-2469 J9 S AFR MED J JI S. Afr. Med. J. PD DEC PY 1993 VL 83 IS 12 BP 885 EP 891 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA ML771 UT WOS:A1993ML77100008 PM 8115913 ER PT J AU SUGG, SL FRAKER, DL ALEXANDER, HR DOPPMAN, JL MILLER, DL CHANG, R SKARULIS, MC MARX, SJ SPIEGEL, AM NORTON, JA COHN, K CLARK, OH THOMPSON, NW AF SUGG, SL FRAKER, DL ALEXANDER, HR DOPPMAN, JL MILLER, DL CHANG, R SKARULIS, MC MARX, SJ SPIEGEL, AM NORTON, JA COHN, K CLARK, OH THOMPSON, NW TI PROSPECTIVE EVALUATION OF SELECTIVE VENOUS SAMPLING FOR PARATHYROID-HORMONE CONCENTRATION IN PATIENTS UNDERGOING REOPERATIONS FOR PRIMARY HYPERPARATHYROIDISM SO SURGERY LA English DT Article; Proceedings Paper CT 14th Annual Meeting of the American-Association-of-Endocrine-Surgeons CY APR 25-27, 1993 CL WILLIAMSBURG, VA SP AMER ASSOC ENDOCRINE SURGEONS ID RECURRENT PRIMARY HYPERPARATHYROIDISM; PREOPERATIVE LOCALIZATION; UNDERGONE SURGERY; PERSISTENT; MANAGEMENT; EXPLORATION; STRATEGY; ADENOMAS; TUMORS AB Background. The utility of standard radiologic imaging studies in guiding reoperative parathyroid surgery for primary hyperparathyroidism is widely known and accepted. The additional information gained by selective venous sampling in that patient population has not been well defined. We report the results of our experience with this method. Methods. Between 1982 and 1992, 223 consecutive patients underwent reoperations for persistent or recurrent primary hyperparathyroidism after a prospectively determined series of imaging studies. Patients underwent noninvasive testing consisting of ultrasonography, computed tomography, technetium thallium scanning, and magnetic resonance imaging. Patients with negative, equivocal, or discordant results on the noninvasive studies proceeded to angiography. If angiography was negative, selective venous sampling was performed. Results. Eighty-six patients (39%) with negative or equivocal noninvasive test and angiogram results underwent selective venous sampling. Seventy-six patients (88%) had a significant gradient in levels of parathyroid hormone from veins draining the left side of the neck (n = 25), the right side of the neck (n = 33), both sides of the neck (n = 7), and the thymus (n = 11). Correlation of these findings with operative findings revealed a sensitivity of 88% and a specificity of 86%. In the subgroup of patients who underwent venous sampling and had completely negative results of standard radiologic studies (35 of 86; 40%), 28 patients (80%) had venous gradients and seven patients (20%) had no gradient. Of those 28 patients in whom the venous sampling gradients were the only positive localization study, the venous samplings were helpful in 23 patients (true positive gradients), and the operative success rate was 93%. In the seven patients with no positive preoperative localizing studies including venous sampling, there were two operative failures (operative success, 71%). Conclusions. Our results show that selective venous sampling is a highly sensitive and specific method to regionally localize abnormal parathyroid glands not imaged by standard noninvasive and invasive radiologic techniques. Venous sampling is the study of choice in guiding reoperative procedures for occult abnormal parathyroid glands that are undetected despite the use of all available imaging studies. C1 NCI,SURG BRANCH,SURG METAB SECT,BLDG 10,ROOM 2B07,BETHESDA,MD 20892. HENRY H JACKSON FDN,ROCKVILLE,MD. WASHINGTON UNIV,SCH MED,DEPT SURG,ST LOUIS,MO 63110. NIDDKDR,CTR CLIN,METAB DIS BRANCH,BETHESDA,MD. NR 24 TC 42 Z9 42 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1993 VL 114 IS 6 BP 1004 EP 1010 PG 7 WC Surgery SC Surgery GA MK900 UT WOS:A1993MK90000003 PM 8256203 ER PT J AU ZEIGER, MA FRAKER, DL PASS, HI NIEMAN, LK CUTLER, GB CHROUSOS, GP NORTON, JA MERRELL, RC PASIEKA, JL KAPLAN, E CLARK, OH ANDERSEN, D THOMPSON, NW AF ZEIGER, MA FRAKER, DL PASS, HI NIEMAN, LK CUTLER, GB CHROUSOS, GP NORTON, JA MERRELL, RC PASIEKA, JL KAPLAN, E CLARK, OH ANDERSEN, D THOMPSON, NW TI EFFECTIVE REVERSIBILITY OF THE SIGNS AND SYMPTOMS OF HYPERCORTISOLISM BY BILATERAL ADRENALECTOMY SO SURGERY LA English DT Article; Proceedings Paper CT 14th Annual Meeting of the American-Association-of-Endocrine-Surgeons CY APR 25-27, 1993 CL WILLIAMSBURG, VA SP AMER ASSOC ENDOCRINE SURGEONS ID CUSHINGS-DISEASE; EXPERIENCE AB Background. The long-term outcome of bilateral adrenalectomy in the management of patients with Cushing's syndrome has not been previously well studied. Methods. We reviewed our long-term results in 34 patients treated with bilateral adrenalectomy between 1983 and the present. Fourteen presented with occult or metastatic ectopic adrenocorticotropic hormone (ACTH) syndrome, 10 with failed treatment of Cushing's disease, five with primary micronodular and four with massive macronodular adrenocortical disease and one with indeterminate cause of Cushing's syndrome. Results. All patients underwent bilateral adrenalectomy. Of 19 patients who required antihypertensive medications before operation, 15 (79%) had significant improvement and were either off all antihypertensive medication or required less medication after operation. Of 7 patients who required medications for diabetes mellitus, after operation 6 (86%) required no medication or changed from injections to oral hypoglycemic agents. Of 9 patients with mood changes or depression, the symptoms of 8 (88%) resolved. Of 2.9 patients with documented weight gain, 23 (79%) showed marked weight loss. Of 13 hirsute patients, 10 (77%) had resolutions of symptoms. Of 21 patients with complaints of fatigue, the symptoms of 16 (76%) resolved. Of 8 women with amenorrhea, 6 (75%) had resolution of symptoms. Each patient in the primary adrenocortical disease group, except one with residual fatigue, had complete resolution of his or her symptoms. There was no difference in resolution of symptoms between the ectopic ACTH and Cushing's disease groups. Six patients die& in the ectopic ACTH group one died of suicide at 1 month, and four of metastatic tumor at 9, 24, 25, and 48 months, and the patient with macronodular adrenocortical hyperplasia died of a myocardial infarction at 30 months. The remainder of the patients have been followed for a mean of 32 months (3 to 67 months). None of the patients had any evidence of recurrent hypercortisolism. Conclusions. We conclude that bilateral adrenalectomy is a safe, effective, and long-lasting method to ameliorate the devastating signs and symptoms of hypercortisolism in patients with Cushing's syndrome. C1 NCI,SURG BRANCH,SURG METAB SECT,BLDG 10,ROOM 2B07,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 11 TC 33 Z9 38 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1993 VL 114 IS 6 BP 1138 EP 1143 PG 6 WC Surgery SC Surgery GA MK900 UT WOS:A1993MK90000023 PM 8256220 ER PT J AU POMMIER, RF VETTO, JT BILLINGSLY, K WOLTERING, EA BRENNAN, MF THOMPSON, NW PROYE, C GRANT, C AF POMMIER, RF VETTO, JT BILLINGSLY, K WOLTERING, EA BRENNAN, MF THOMPSON, NW PROYE, C GRANT, C TI COMPARISON OF ADRENAL AND EXTRAADRENAL PHEOCHROMOCYTOMAS SO SURGERY LA English DT Article; Proceedings Paper CT 14th Annual Meeting of the American-Association-of-Endocrine-Surgeons CY APR 25-27, 1993 CL WILLIAMSBURG, VA SP AMER ASSOC ENDOCRINE SURGEONS AB Background. It is commonly believed that extraadrenal tumors (EAT) of the paraganglion system are more likely to be malignant than adrenal tumors (A T) and carry a poorer prognosis. We analyzed 73 paraganglion tumors (PT) to determine whether EATs are more likely to be malignant or have a poorer prognosis than ATs. Methods. A review of patients with PTs at three institutions was performed. Malignant tumors were defined as those that metastasized. Comparison of the frequencies of malignant tumors was performed by chi-squared analysis. Survival distributions were determined by Kaplan and Meier analysis. Comparison of survival distributions was performed by log-rank analysis. Results. There were 73 patients. There were 51 ATs, of which 24 were malignant, and 22 EATs, of which 11 were malignant (p = 0.82). The 5-year survival rate was 77% for patients with ATs and 82% for patients with EATs (p = 0.29). The 5-year survival rate for patients with malignant ATs was 57%, and 74% for patients with malignant EATs (p = 0.15). There were no significant differences in disease-free survival rates on the basis of tumor site. Conclusions. We were unable to demonstrate that EATs are significantly more likely to be malignant than ATs. The survival and disease-free survival rates for malignant ATs and EATs are similar, and among malignant tumors, there may be no prognostic value of the anatomic location. C1 NCI,DEPT SURG,BETHESDA,MD 20892. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. RP POMMIER, RF (reprint author), OREGON HLTH SCI UNIV,DEPT SURG,3181 SW SAM JACKSON PK RD,L223A,PORTLAND,OR 97201, USA. NR 10 TC 38 Z9 40 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1993 VL 114 IS 6 BP 1160 EP 1166 PG 7 WC Surgery SC Surgery GA MK900 UT WOS:A1993MK90000027 PM 8256223 ER PT J AU NI, Q XU, H PARTILLA, JS STARK, PA CARROLL, FI BRINE, GA ROTHMAN, RB AF NI, Q XU, H PARTILLA, JS STARK, PA CARROLL, FI BRINE, GA ROTHMAN, RB TI STEREOCHEMICAL REQUIREMENTS FOR PSEUDOIRREVERSIBLE INHIBITION OF OPIOID MU RECEPTOR-BINDING BY THE 3-METHYLFENTANYL CONGENERS, RTI-46144 AND ITS ENANTIOMERS - EVIDENCE FOR DIFFERENT BINDING DOMAINS SO SYNAPSE LA English DT Article DE MU-RECEPTORS; OPIOID RECEPTORS; FENTANYL; RECEPTOR BINDING ID RAT-BRAIN; PSEUDOALLOSTERIC MODULATION; LIGAND-BINDING; OPIATE; SITES; (+)-CIS-3-METHYLFENTANYL; AFFINITY; COMPLEX; IDENTIFICATION; TRANSPORTER AB Fentanyl and its congeners are of interest not only because of their clinical applications, but also because certain members of this series of opioid analgesics exhibit unique properties, such as acting as pseudoirreversible inhibitors of mu receptor binding, both in vitro and in vivo. Previous studies showed that pretreatment of membranes with (+)-cis-3-methylfentanyl resulted in a lower affinity interaction of [H-3]ohm-efentanyl with the mu binding site, as well as an increased dissociation rate. The present study was undertaken to determine the stereochemical requirements for pseudoirreversible inhibition of mu receptor binding using the methylfentanyl congeners, (+/-)-cis-N-[1-(2-hydroxy-2-phenylethyl)-3-methyl-4-piperidyl]-N-phenylpropanamide HCl (RTI-4614-4) and its four resolved enantiomers. A R configuration of the 2-hydroxy group was essential for high affinity binding and pseudoirreversible inhibition. The two enantiomers with this configuration, 1b ((2R,3R,4S)-N-[1-(2-hydroxy-2-phenylethyl)-3-methyl-4-piperidyl]-N-phenylpropanamide oxalate) and 1c ((2R,3S,4R)-N-[1-(2-hydroxy-2-phenylethyl)-3-methyl-4-piperidyl]-N-phenylpropanamide HCl), acted as pseudoirreversible inhibitors of the mu receptor as labeled with [H-3][D-Ala2-MePhe4,Gly-ol5]enkephalin, [H-3]fentanyl or [H-3]etorphine. RTI-4614-4, 1b, and 1c decreased the Bmax of [H-3][D-Ala2-MePhe4,Gly-ol5]enkephalin binding sites without altering the dissociation rate. These drugs had a lesser effect on steady-state [H-3]fentanyl and [H-3]etorphine binding but did produce statistically significant changes in the parameters of the two-component dissociation model, which accurately described the dissociation of these [H-3]ligands. Viewed collectively, these data indicate that the mechanism of the pseudoirreversible inhibition appears to depend on the radioligand used to label the mu receptor. To explain these data, a pseudoallosteric model is proposed that postulates that certain mu ligands bind to different domains of the drug recognition site of the mu receptor and that the prebinding of pseudoirreversible inhibitors to the recognition site changes the domains available to a radioligand, leading to alterations in steady-state binding levels and dissociation kinetics. (C) 1993 Wiley-Liss, Inc. C1 NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,POB 5180,BALTIMORE,MD 21224. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NR 34 TC 11 Z9 11 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD DEC PY 1993 VL 15 IS 4 BP 296 EP 306 DI 10.1002/syn.890150406 PG 11 WC Neurosciences SC Neurosciences & Neurology GA MJ928 UT WOS:A1993MJ92800005 PM 8153877 ER PT J AU CONE, EJ HUESTIS, MA AF CONE, EJ HUESTIS, MA TI RELATING BLOOD-CONCENTRATIONS OF TETRAHYDROCANNABINOL AND METABOLITES TO PHARMACOLOGICAL EFFECTS AND TIME OF MARIJUANA USAGE SO THERAPEUTIC DRUG MONITORING LA English DT Article; Proceedings Paper CT 3RD INTERNATIONAL CONGRESS OF THERAPEUTIC DRUG MONITORING AND CLINICAL TOXICOLOGY CY MAY 25-28, 1993 CL PHILADELPHIA, PA SP INT ASSOC THERAPEUT DRUG MONITORING & CLIN TOXICOL DE MARIJUANA; TETRAHYDROCANNABINOL; PHARMACOKINETICS; PHARMACODYNAMICS; FORENSIC DRUG TESTING ID SMOKING MARIJUANA; DELTA-9-TETRAHYDROCANNABINOL; CANNABINOIDS; DISPOSITION; SPECTROMETRY; ABSORPTION; KINETICS; THCCOOH; HEAVY; USERS AB Pharmacokinetic and pharmacodynamic analyses of marijuana data have provided new insights into the relationship of blood concentrations of tetrahydrocannabinol (THC) and metabolites to drug-induced effects. THC is rapidly absorbed and distributed to tissues; initial changes in blood concentrations are out of phase (hysteresis) with physiological and behavioral changes. Once blood/tissue equilibrium is established, a direct correlation of THC blood concentration and effect is observed. Various pharmacodynamic models provide concentration estimates in the range of 7-29 ng/ml for amount of THC in blood necessary for production of 50% of maximal subjective high effect. Also, models have been proposed for predicting the time of marijuana exposure from plasma concentrations of THC and THC-carboxy acid metabolite (THCCOOH). These models were based on data from a controlled clinical study of marijuana smoking. Such models allow prediction of the elapsed time since marijuana use based on analysis for cannabinoids from a single plasma sample and provide accompanying 95% confidence intervals around the prediction. These models may be beneficial to forensic scientists in their interpretation of cannabinoid blood data associated with accidents, criminal investigations, and traffic violations. RP CONE, EJ (reprint author), NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224, USA. NR 23 TC 42 Z9 48 U1 3 U2 8 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0163-4356 J9 THER DRUG MONIT JI Ther. Drug Monit. PD DEC PY 1993 VL 15 IS 6 BP 527 EP 532 DI 10.1097/00007691-199312000-00013 PG 6 WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology GA MH845 UT WOS:A1993MH84500013 PM 8122288 ER PT J AU ERASMUS, RT SAVORY, J WILLS, MR HERMAN, MM AF ERASMUS, RT SAVORY, J WILLS, MR HERMAN, MM TI ALUMINUM NEUROTOXICITY IN EXPERIMENTAL-ANIMALS SO THERAPEUTIC DRUG MONITORING LA English DT Article; Proceedings Paper CT 3RD INTERNATIONAL CONGRESS OF THERAPEUTIC DRUG MONITORING AND CLINICAL TOXICOLOGY CY MAY 25-28, 1993 CL PHILADELPHIA, PA SP INT ASSOC THERAPEUT DRUG MONITORING & CLIN TOXICOL DE ALUMINUM; NEUROTOXICITY; NEURODEGENERATION ID ALZHEIMERS-DISEASE; NEUROFIBRILLARY DEGENERATION; BRAIN; EXPOSURE; MALTOL; IRON; RAT; ENCEPHALOPATHY; ACCUMULATION; PEROXIDATION AB Neurotoxic effects of aluminum (Al) were recognized >100 years ago, but have only recently been studied in detail. By far, the most dramatic effect of Al is that of producing intraneuronal perikaryal neurofilamentous aggregates, which consist of phosphorylated neurofilaments. Several species have been used to demonstrate this effect, rabbit being most common; the effect also is seen in in vitro systems. Besides its role in producing neurofibrillary pathology, Al appears to modify the blood-brain barrier and exert cholinergic and noradrenergic effects. Possible mechanisms of Al neurotoxicity could be related to cell damage via free radical production, impairment of glucose metabolism, and effects on signal transduction. C1 UNIV VIRGINIA,HLTH SCI CTR,DEPT PATHOL,BOX 168,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,HLTH SCI CTR,DEPT INTERNAL MED,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,HLTH SCI CTR,DEPT BIOCHEM,CHARLOTTESVILLE,VA 22908. NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,NEUROPATHOL SECT,WASHINGTON,DC 20032. UNIV PAPUA NEW GUINEA,DEPT PATHOL,PORT MORESBY,PAPUA N GUINEA. NR 41 TC 36 Z9 36 U1 0 U2 5 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0163-4356 J9 THER DRUG MONIT JI Ther. Drug Monit. PD DEC PY 1993 VL 15 IS 6 BP 588 EP 592 DI 10.1097/00007691-199312000-00024 PG 5 WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology GA MH845 UT WOS:A1993MH84500024 PM 8122299 ER PT J AU KADIISKA, MB HANNA, PM MASON, RP AF KADIISKA, MB HANNA, PM MASON, RP TI IN-VIVO ESR SPIN-TRAPPING EVIDENCE FOR HYDROXYL RADICAL-MEDIATED TOXICITY OF PARAQUAT AND COPPER IN RATS SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID ESCHERICHIA-COLI; SUPEROXIDE FORMATION; LIPID-PEROXIDATION; HYDROGEN-PEROXIDE; OXYGEN; MECHANISM; IRON; LUNG; MICE; HEPATOCYTES C1 BULGARIAN ACAD SCI,INST PHYSIOL,BU-1113 SOFIA,BULGARIA. RP KADIISKA, MB (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 37 TC 21 Z9 22 U1 0 U2 7 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD DEC PY 1993 VL 123 IS 2 BP 187 EP 192 DI 10.1006/taap.1993.1236 PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA MK527 UT WOS:A1993MK52700002 PM 8248925 ER PT J AU VERSCHOYLE, RD PHILPOT, RM WOLF, CR DINSDALE, D AF VERSCHOYLE, RD PHILPOT, RM WOLF, CR DINSDALE, D TI CYP4B1 ACTIVATES 4-IPOMEANOL IN RAT LUNG SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID P-450-DEPENDENT MONOOXYGENASE SYSTEM; SPECIES-DEPENDENT EXPRESSION; DAMAGED SWEET-POTATOES; METABOLIC-ACTIVATION; COVALENT BINDING; CYTOCHROME-P-450 ISOZYME-5; PULMONARY CYTOCHROME-P-450; RABBIT PULMONARY; PARA-XYLENE; 4-IPOMEANOL C1 NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709. UNIV DUNDEE,NINEWELLS HOSP & MED SCH,BIOMED RES CTR,ICRF,MOLEC PHARMACOL UNIT,DUNDEE DD1 9SY,ANGUS,SCOTLAND. RP VERSCHOYLE, RD (reprint author), MRC LABS,TOXICOL UNIT,WOODMANSTERNE RD,CARSHALTON SM5 4EF,SURREY,ENGLAND. NR 29 TC 38 Z9 39 U1 3 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD DEC PY 1993 VL 123 IS 2 BP 193 EP 198 DI 10.1006/taap.1993.1237 PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA MK527 UT WOS:A1993MK52700003 PM 8248926 ER PT J AU PARK, MH WOLFF, EC FOLK, JE AF PARK, MH WOLFF, EC FOLK, JE TI IS HYPUSINE ESSENTIAL FOR EUKARYOTIC CELL-PROLIFERATION SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID INITIATION-FACTOR EIF-4D; HAMSTER OVARY CELLS; PROTEIN-SYNTHESIS; AMINO-ACID; DEOXYHYPUSINE; SPERMIDINE; PRECURSOR; IDENTIFICATION; POLYAMINES; BIOSYNTHESIS AB Hypusine [N(epsilon)-(4-amino-2-hydroxybutyl)-L-lysine] is a most remarkable amino acid, occurring in all eukaryotic cells, yet occupying only a single position in one protein, eukaryotic protein synthesis initiation factor 5A (eIF-5A). The unusual structure of hypusine, its derivation from the polyamine spermidine, and its increased formation in response to growth stimulation, as well as its limited occurrence in the highly conserved amino acid sequence of eIF-5A, have aroused keen interest in the biological significance of its existence and in its relationship to eIF-5A function. RP PARK, MH (reprint author), NIDR,ENZYME CHEM SECT,CELLULAR DEV & ONCOL LAB,BLDG 30,ROOM 211,BETHESDA,MD 20892, USA. NR 32 TC 142 Z9 150 U1 0 U2 4 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 DEC PY 1993 VL 18 IS 12 BP 475 EP 479 DI 10.1016/0968-0004(93)90010-K PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MM513 UT WOS:A1993MM51300010 PM 8108861 ER PT J AU HENGEN, PN AF HENGEN, PN TI METHODS AND REAGENTS SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article RP HENGEN, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 0 TC 1 Z9 1 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 DEC PY 1993 VL 18 IS 12 BP 484 EP 485 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MM513 UT WOS:A1993MM51300012 PM 8108863 ER PT J AU DHAWAN, S WEEKS, BS ABBASI, F GRALNICK, HR NOTKINS, AL KLOTMAN, ME YAMADA, KM KLOTMAN, PE AF DHAWAN, S WEEKS, BS ABBASI, F GRALNICK, HR NOTKINS, AL KLOTMAN, ME YAMADA, KM KLOTMAN, PE TI INCREASED EXPRESSION OF ALPHA-4-BETA-1 AND ALPHA-5-BETA-1 INTEGRINS ON HTLV-1-INFECTED LYMPHOCYTES SO VIROLOGY LA English DT Note ID TROPICAL SPASTIC PARAPARESIS; T-CELL RECOGNITION; HTLV-I; ADHESION MOLECULES; FIBRONECTIN; VIRUS; ANTIBODIES; RECEPTOR; BINDING; VLA-4 C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NCI,CTR CLIN,HEMATOL SERV,BETHESDA,MD 20892. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RP DHAWAN, S (reprint author), US FDA,MOLEC VIROL LAB,ROCKVILLE,MD 20852, USA. RI klotman, mary/A-1921-2016 NR 32 TC 32 Z9 32 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD DEC PY 1993 VL 197 IS 2 BP 778 EP 781 DI 10.1006/viro.1993.1656 PG 4 WC Virology SC Virology GA MH092 UT WOS:A1993MH09200032 PM 7504369 ER PT J AU NIMS, RW SINCLAIR, PR SINCLAIR, JF DRAGNEV, KH JONES, CR MELLINI, DW THOMAS, PE LUBET, RA AF NIMS, RW SINCLAIR, PR SINCLAIR, JF DRAGNEV, KH JONES, CR MELLINI, DW THOMAS, PE LUBET, RA TI DOSE-RESPONSE RELATIONSHIPS FOR THE INDUCTION OF P450 2B BY 1,4-BIS[2-(3,5-DICHLOROPYRIDYLOXY)]BENZENE (TCPOBOP) IN RAT AND CULTURED RAT HEPATOCYTES SO XENOBIOTICA LA English DT Article ID CYTOCHROME-P-450 GENE-EXPRESSION; GLUTATHIONE S-TRANSFERASES; PHENOBARBITAL-LIKE INDUCER; MONO-OXYGENASE ACTIVITY; MESSENGER-RNAS; NUCLEOTIDE-SEQUENCE; FLUOROMETRIC ASSAY; ISOZYMES; QUANTITATION; DEALKYLATION AB 1. The dose-response relationships for hepatic CYP2B induction by 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) were examined in the male F344/NCr rat. TCPOBOP, administered for 14 days at 0-1000 ppm in the diet, caused concentration-dependent induction of hepatic CYP2B1 protein and RNA, and of CYP2B-mediated catalytic activities (benzyloxy- and pentoxyresorufin O-dealkylation, and testosterone 16beta-hydroxylation). ED50 values for CYP2B induction were greater-than-or-equal-to 300 ppm dietary TCPOBOP. The maximal inductions observed were 66-88% of those resulting from exposure of the rats to 500 ppm dietary phenobarbital. 2. The EC50 values for hepatic CYP2B induction were 1.5-3.0 mum (based on serum TCPOBOP) and 15-20 mumol/kg liver. 3. The maximal inductions of isozymes of the CYP3A subfamily, of microsomal epoxide hydrolase, and of glutathione S-transferases Ya/Yc and Yb1/Yb2 in rats exposed to TCPOBOP were 58-74% of those resulting from exposure of the rats to 500 ppm dietary phenobarbital. 4. The ED50 value for induction of benzyloxyresorufin O-dealkylation in cultured rat hepatocytes by TCPOBOP was determined to be 0.93 mum. The maximal induction of this activity caused by TCPOBOP was 87% of the maximum increases caused by phenobarbital. 5. The results indicate that TCPOBOP is a highly effective phenobarbital-type inducer in the rat when administered in the diet for 2 weeks at 1000 ppm. When extent of induction is related to serum total xenobiotic level, TCPOBOP would appear to be at least as potent as, if not more potent than, phenobarbital in the rat. C1 VET ADM MED CTR,WHITE RIVER JCT,VT 05009. NCI,FCRDC,PRI DYNCORP,CHEM SYNTHESIS & ANAL LAB,FREDERICK,MD 21702. RUTGERS UNIV,COLL PHARM,DEPT CHEM BIOL,PISCATAWAY,NJ 08855. RP NIMS, RW (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,CHEM SECT,BLDG 538,ROOM 205E,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102, CA25012] NR 36 TC 22 Z9 22 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD DEC PY 1993 VL 23 IS 12 BP 1411 EP 1426 PG 16 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA MP250 UT WOS:A1993MP25000008 PM 7510916 ER PT J AU CRAWLEY, JN AF CRAWLEY, JN TI FUNCTIONAL INTERACTIONS OF GALANIN AND ACETYLCHOLINE - RELEVANCE TO MEMORY AND ALZHEIMERS-DISEASE SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE ALZHEIMERS DISEASE; MEMORY; LEARNING; HIPPOCAMPUS; NEUROPEPTIDE; COEXISTENCE; CHOLINERGIC; GALANIN ID RAT VENTRAL HIPPOCAMPUS; CENTRAL-NERVOUS-SYSTEM; LOCUS-CERULEUS NEURONS; SUBSTANCE-P; PHOSPHOINOSITIDE TURNOVER; PARKINSONS-DISEASE; SPINAL-CORD; TYROSINE-HYDROXYLASE; INSITU HYBRIDIZATION; PERIPHERAL AXOTOMY AB Galanin, a 29-amino acid neuropeptide, is the only peptide known to coexist with acetylcholine in the basal forebrain neurons which degenerate early in the progression of Alzheimer's disease. Biochemical and neurophysiological studies demonstrated inhibitory actions of galanin on cholinergic functions. Behavioral investigations found that intracerebrally administered galanin produces deficits on spatial learning and memory tasks in rats. Taken together, the current literature suggests that galanin acts as an inhibitory modulator of acetylcholine in this coexistence. Particularly in the case of Alzheimer's disease, where cholinergic activity is severely compromised, the negative actions of galanin may be particularly deleterious. Recently developed galanin antagonists may provide a novel therapeutic approach toward enhancing memory processes in Alzheimer's disease, by removing the putative inhibitory actions of endogenous galanin on the remaining basal forebrain cholinergic neurons. RP CRAWLEY, JN (reprint author), NIMH,EXPTL THERAPEUT BRANCH,BEHAV NEUROPHARMACOL SECT,BLDG 10,ROOM 4N214,BETHESDA,MD 20892, USA. NR 81 TC 50 Z9 50 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD NOV 30 PY 1993 VL 57 IS 2 BP 133 EP 141 DI 10.1016/0166-4328(93)90129-E PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA MQ471 UT WOS:A1993MQ47100004 PM 7509609 ER PT J AU WALLACE, W HAROUTUNIAN, V AF WALLACE, W HAROUTUNIAN, V TI USING THE SUBCORTICALLY LESIONED RAT CORTEX TO UNDERSTAND THE PHYSIOLOGICAL-ROLE OF AMYLOID PRECURSOR PROTEIN SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE SUBCORTICAL LESION; AMYLOID PRECURSOR PROTEIN; NUCLEUS BASALIS OF MEYNERT; CHOLINERGIC SYSTEM; GENE INDUCTION; ACETYLCHOLINE; NOREPINEPHRINE; SEROTONIN ID ALZHEIMERS-DISEASE; TRANSGENIC MICE; CEREBRAL-CORTEX; NUCLEUS BASALIS; SENILE DEMENTIA; BETA PROTEIN; NEURONS; BRAIN; IMMUNOREACTIVITY; FOREBRAIN AB Alzheimer's disease pathology is characterized by the presence of neuritic plaques and neurofibrillary tangles and specific neurotransmitter deficits in the cortex and hippocampus. Advances in the understanding of Alzheimer's disease have been hampered by the absence of appropriate animal model systems. Most in vivo rodent models have turned to aged animals, animals with experimentally induced lesions of various neurotransmitter systems, animals with pharmacologically induced neurotransmitter perturbations, and mice made transgenic for genes related to amyloid precursor protein. These models have been useful for the investigation of some discrete aspects of Alzheimer's disease, including deficits in forebrain cholinergic activity and the resulting cognitive deficits. However, none of these models have led to the development of the principal neuropathological hallmarks of Alzheimer's disease, neuritic plaques and neurofibrillary tangles. Furthermore, the relationship, if any, between the reduction of neurotransmitter activity and the formation of neuritic plaques and neurofibrillary tangles is unknown. The subcortically lesioned rat model system which we have used approximates the cortical neurotransmitter and the cognitive deficits of Alzheimer's disease. We have recently found that these same subcortical neurotransmitter system lesions alter the expression of amyloid precursor protein, the precursor of beta amyloid peptide, which is the principal component of neuritic plaques. Loss of functional subcortical innervation by either permanent lesions or transient inhibition of cortical neurotransmitter (acetylcholine) release resulted in the induction of amyloid precursor protein in the cortex. The induction was rapid and persistent with the permanent lesions or reversible with the transient inhibition. Lesions of cholinergic, serotonergic, and adrenergic neurotransmitter systems all resulted in the induction. The induction was accompanied by elevated secretion of amyloid precursor protein as evidenced by elevated levels of the secreted form of the protein in the cerebrospinal fluid of the lesioned animals. Although this alteration does not lead to formation of neuritic plaques in the brain, this animal represents a powerful model for investigating the normal physiological role of amyloid precursor protein in vivo and provides a means for integrating the relationship between neurotransmitter deficits, expression of amyloid precursor protein, and formation of neuritic plaques. C1 VET ADM MED CTR,DEPT PSYCHIAT,BRONX,NY 10468. CUNY MT SINAI SCH MED,DEPT PSYCHIAT,NEW YORK,NY 10029. RP WALLACE, W (reprint author), NIMH,ST ELIZABETHS HOSP,BIOCHEM GENET LAB,WASHINGTON,DC 20032, USA. NR 30 TC 10 Z9 10 U1 0 U2 0 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 NOV 30 PY 1993 VL 57 IS 2 BP 199 EP 206 DI 10.1016/0166-4328(93)90136-E PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA MQ471 UT WOS:A1993MQ47100011 PM 8117425 ER PT J AU SAUNDERS, NA SMITH, RJ JETTEN, AM AF SAUNDERS, NA SMITH, RJ JETTEN, AM TI REGULATION OF PROLIFERATION-SPECIFIC AND DIFFERENTIATION-SPECIFIC GENES DURING SENESCENCE OF HUMAN EPIDERMAL KERATINOCYTE AND MAMMARY EPITHELIAL-CELLS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID REPLICATIVE SENESCENCE; CELLULAR SENESCENCE; BINDING PROTEIN; EXPRESSION; CDC2; E2F C1 NIEHS,CELL BIOL SECT,PULM PATHOBIOL LAB,POB 12233,RES TRIANGLE PK,NC 27709. RI saunders, nicholas/E-1544-2014; McTaggart, Jill/G-4696-2010; OI saunders, nicholas/0000-0002-2478-3420; McTaggart, Jill/0000-0002-9000-8529; Jetten, Anton/0000-0003-0954-4445 NR 24 TC 53 Z9 53 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 NOV 30 PY 1993 VL 197 IS 1 BP 46 EP 54 DI 10.1006/bbrc.1993.2439 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MJ884 UT WOS:A1993MJ88400008 PM 7902715 ER PT J AU GLASS, RS SINGH, WP JUNG, W VERES, Z SCHOLZ, TD STADTMAN, TC AF GLASS, RS SINGH, WP JUNG, W VERES, Z SCHOLZ, TD STADTMAN, TC TI MONOSELENOPHOSPHATE - SYNTHESIS, CHARACTERIZATION, AND IDENTITY WITH THE PROKARYOTIC BIOLOGICAL SELENIUM DONOR, COMPOUND SEPX SO BIOCHEMISTRY LA English DT Note ID NUCLEAR MAGNETIC-RESONANCE; SELD GENE-PRODUCT; ESCHERICHIA-COLI; TRANSFER-RNAS; SALMONELLA-TYPHIMURIUM; ADENINE-NUCLEOTIDES; PHOSPHORUS; 5-METHYLAMINOMETHYL-2-SELENOURIDINE; NUCLEOSIDE; ESTERS AB A labile, selenium donor compound required for synthesis of selenium-dependent enzymes and seleno-tRNAs is formed from ATP and selenide by the SELD enzyme. This compound, tentatively identified as a selenophosphate [Veres, Z., Tsai, L., Scholz, T. D., Politino, M., Balaban, R. S., & Stadtman, T. C. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 2975-2979], is indistinguishable from chemically prepared monoselenophosphate by P-31 NMR spectroscopy and ion pairing HPLC. Furthermore, addition of chemically prepared monoselenophosphate caused a dose-dependent decrease in the amount of Se-75 incorporated into tRNAs from (SePX)-Se-75 generated in situ by SELD enzyme. A procedure is described for the chemical synthesis of monoselenophosphate in which the readily prepared (MeO)3PSe is converted in quantitative yield to (TMSO)3PSe followed by complete cleavage of the latter to monoselenophosphate in oxygen-free aqueous buffer. The chemical properties of chemically synthesized monoselenophosphate are described. C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NHLBI,CARDIAC ENERGET LAB,BETHESDA,MD 20892. HUNGARIAN ACAD SCI,CENT RES INST CHEM,H-1025 BUDAPEST,HUNGARY. RP GLASS, RS (reprint author), UNIV ARIZONA,DEPT CHEM,TUCSON,AZ 85721, USA. NR 30 TC 99 Z9 102 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 NOV 30 PY 1993 VL 32 IS 47 BP 12555 EP 12559 DI 10.1021/bi00210a001 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MJ990 UT WOS:A1993MJ99000001 PM 8251472 ER PT J AU BALAJI, PV QASBA, PK RAO, VSR AF BALAJI, PV QASBA, PK RAO, VSR TI MOLECULAR-DYNAMICS SIMULATIONS OF ASIALOGLYCOPROTEIN RECEPTOR LIGANDS SO BIOCHEMISTRY LA English DT Article ID MONOFUCOSYLATED BIANTENNARY GLYCAN; N-ACETYLLACTOSAMINE TYPE; TRIANTENNARY GLYCOPEPTIDE; 3-DIMENSIONAL STRUCTURES; CONFORMATIONAL-ANALYSIS; GLYCOSIDIC LINKAGE; DATA-BANK; OLIGOSACCHARIDES; BINDING; DISACCHARIDES AB Several recent studies have implicated carbohydrates in cell adhesion, inflammation, clearance of glycoproteins from blood circulation, embryonic development, and metastasis among others. Understanding the conformation of these carbohydrate recognition elements and their interaction at the molecular level is essential for the design of oligosaccharide inhibitors/drugs. Given the difficulty in solving carbohydrate structures by X-ray crystallography and since NMR experiments give only time-averaged conformation, molecular dynamics simulations are well suited to determine all the accessible conformations of oligosaccharides. Present communication reports the simulation of some of the oligosaccharide ligands of asialoglycoprotein receptor for 1 ns using Biosym's InsightII molecular modeling package on NCI-FCRDC's Y-MP 8D/8128 supercomputer. Results obtained from these simulations, in addition to explaining the observed differences in the binding affinities of these ligands to the asialoglycoprotein receptor, have led to a modified model for the recognition of the oligosaccharides by the receptor. Accordingly, only the two terminal galactose residues on the 1,3-arm of the triantennary oligosaccharide (GlcNAc2Man3 core of the N-linked oligosaccharides with N-acetyllactosamine in beta1,2- and beta1,4-linkages on the 1,3-linked core mannose) are primarily required for recognition, and the terminal galactose on the 1,6-arm (N-acetyllactosamine in beta1,2-linkage on the 1,6-linked core mannose) provides additional binding energy. It has been shown that the oligosaccharides studied here have significant flexibility and the flexibility is more around the 1,3-linkage than the 1,6-linkage. The need for simulation for longer periods and with multiple initial conformations is also discussed in the present report. C1 NCI, MATH BIOL LAB,BLDG PK 5,ROOM 410, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. OI Balaji, Petety/0000-0002-6018-6957 NR 41 TC 27 Z9 27 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 30 PY 1993 VL 32 IS 47 BP 12599 EP 12611 DI 10.1021/bi00210a008 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MJ990 UT WOS:A1993MJ99000008 PM 8251478 ER PT J AU OGISO, Y HWANG, YW SHIH, TY KUZUMAKI, N AF OGISO, Y HWANG, YW SHIH, TY KUZUMAKI, N TI BIOLOGICAL-ACTIVITY OF A K-RAS MUTANT THAT CONTAINS THE 12R/59T/116Y-MUTATIONS SO CANCER LETTERS LA English DT Article DE DOMINANT NEGATIVE MUTATION; RAS ONCOGENE; TUMOR SUPPRESSION ID GENE-PRODUCT; SACCHAROMYCES-CEREVISIAE; KIRSTEN-RAS; N-RAS; P21; NEUROFIBROMATOSIS; PROTEIN; MUTATIONS; GTPASE; DOMAIN AB The 12R/59T/116Y mutations have been shown to confer a dominant negative activity on H-ras oncogene (H-ras 116Y). To determine whether this event is unique for H-ras, we introduced the same mutations into K-ras oncogene. This mutant, K-ras 116Y, suppressed transformed phenotypes induced by overexpression of H-ras proto-oncogene. NIH3T3 cells expressing K-ras 116Y were resistant to transformation by v-fes oncogene. Analysis of chimaeras between H- and K-ras 116Y showed that the C-terminal variable region determines the level of suppressor activity. These results suggest that these mutations are applicable to other GDP/GTP binding proteins. C1 NEW YORK STATE INST BASIC RES DEV DISABIL,DEPT MOLEC BIOL,STATEN ISL,NY 10314. NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702. RP OGISO, Y (reprint author), HOKKAIDO UNIV,SCH MED,INST CANC,MOLEC GENET LAB,SAPPORO,HOKKAIDO 060,JAPAN. FU NCI NIH HHS [CA53782] NR 32 TC 6 Z9 6 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 NOV 30 PY 1993 VL 75 IS 1 BP 19 EP 26 DI 10.1016/0304-3835(93)90202-K PG 8 WC Oncology SC Oncology GA MR718 UT WOS:A1993MR71800003 PM 8287379 ER PT J AU BHAT, KS AF BHAT, KS TI GENERATION OF A PLASMID VECTOR FOR DELETION CLONING BY RAPID MULTIPLE SITE-DIRECTED MUTAGENESIS SO GENE LA English DT Note DE DNA SEQUENCING; ESCHERICHIA-COLI; PCR; RESTRICTION ENDONUCLEASE; SUBCLONING ID DNA-SEQUENCE ANALYSIS; M13; FRAGMENTS; SELECTION AB The construction of a new plasmid vector, devoid of all Mbol (GATC) and TspEI(AATT) restriction sites, is described. The lack of these two frequent-cutting restriction sites is a unique feature among plasmids. This new plasmid, pBRkanf1-, allows selective fragmentation of a cloned insert. As a result, the vector offers an alternative strategy to create overlapping and sequentially deleted subclones. In addition, the construction of the new plasmid required the development of a rapid and accurate multiple site-directed mutagenesis procedure. The mutagenesis method uses a combination of DNA amplification and chain extension by DNA polymerase. By this method, mutations are created progressively from one end of a DNA molecule to the other. RP BHAT, KS (reprint author), NIH,ROCKY MT LABS,903 S 4TH ST,HAMILTON,MT 59840, USA. NR 19 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD NOV 30 PY 1993 VL 134 IS 1 BP 83 EP 87 DI 10.1016/0378-1119(93)90177-5 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA MK421 UT WOS:A1993MK42100011 PM 8244035 ER PT J AU BECERRIL, B CORONA, M MEJIA, MC MARTIN, BM LUCAS, S BOLIVAR, F POSSANI, LD AF BECERRIL, B CORONA, M MEJIA, MC MARTIN, BM LUCAS, S BOLIVAR, F POSSANI, LD TI THE GENOMIC REGION ENCODING TOXIN-GAMMA FROM THE SCORPION TITYUS-SERRULATUS CONTAINS AN INTRON SO FEBS LETTERS LA English DT Article DE SCORPION TOXIN; NA+ CHANNEL; GENOMIC DNA CLONE; NUCLEOTIDE SEQUENCE; ARACHNID INTRON; TITYUS SERRULATUS ID VENOM; PURIFICATION; SEQUENCE; MELLO; LUTZ AB The gene encoding toxin gamma from the scorpion, Tityus serrulatus, was amplified by PCR from genomic DNA employing synthetic oligonucleotides designed from the reported cDNA sequence. The nucleotide sequence of this gene reveals the presence of an intron of 475 base pairs (bp) which interrupts the region that encodes the signal peptide of the precursor toxin. A comparison of the intron boundary sequences of the gamma toxin gene with ones from other arachnid genes is also presented. C1 UNIV NACL AUTONOMA MEXICO,INST BIOTECNOL,CUERNAVACA 62271,MORELOS,MEXICO. NIMH,MOLEC NEUROGENET UNIT,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. INST BUTANTAN,SAO PAULO,BRAZIL. RI Possani, Lourival/J-2397-2013; Lucas, Sylvia/L-8777-2013 NR 16 TC 30 Z9 32 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 29 PY 1993 VL 335 IS 1 BP 6 EP 8 DI 10.1016/0014-5793(93)80428-W PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA NJ690 UT WOS:A1993NJ69000002 PM 8243666 ER PT J AU FONTANA, DJ POST, RM PERT, A AF FONTANA, DJ POST, RM PERT, A TI CONDITIONED INCREASES IN MESOLIMBIC DOPAMINE OVERFLOW BY STIMULI ASSOCIATED WITH COCAINE SO BRAIN RESEARCH LA English DT Article DE COCAINE; CONDITIONING; NUCLEUS ACCUMBENS; DOPAMINE ID MEDIAL FOREBRAIN-BUNDLE; FREELY MOVING RATS; NUCLEUS ACCUMBENS; EXTRACELLULAR DOPAMINE; INVIVO MICRODIALYSIS; ROTATIONAL BEHAVIOR; UPTAKE INHIBITION; SELF-STIMULATION; D-AMPHETAMINE; RELEASE AB Stimuli associated with cocaine come to acquire incentive-motivational as well as secondary reinforcing properties which can energize and maintain behavior in laboratory animals as well as precipitate craving in addicts. Environmental stimuli paired with a large dose of cocaine for one training session elicited significant increases in locomotor activity and in extracellular dopamine in the nucleus accumbens of rats during a second test session with a low dose of cocaine. The increases in extracellular dopamine are not likely a secondary consequence of this increase in locomotor output of rats conditioned to cocaine, since doses of MK-801 which produced similar increases in locomotor behavior had no effect on mesolimbic dopamine. These findings provide a neurochemical mechanism for understanding the incentive motivational properties of stimuli associated with cocaine and may help to explain recidivism of cocaine addicts when they return to an environment in which the drug was used. C1 NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 69 TC 107 Z9 108 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 NOV 26 PY 1993 VL 629 IS 1 BP 31 EP 39 DI 10.1016/0006-8993(93)90477-5 PG 9 WC Neurosciences SC Neurosciences & Neurology GA MH057 UT WOS:A1993MH05700005 PM 8287278 ER PT J AU KLING, MA SMITH, MA GLOWA, JR PLUZNIK, D DEMAS, J DEBELLIS, MD GOLD, PW SCHULKIN, J AF KLING, MA SMITH, MA GLOWA, JR PLUZNIK, D DEMAS, J DEBELLIS, MD GOLD, PW SCHULKIN, J TI FACILITATION OF COCAINE KINDLING BY GLUCOCORTICOIDS IN RATS SO BRAIN RESEARCH LA English DT Note DE GLUCOCORTICOID; DEXAMETHASONE; COCAINE; KINDLING; SENSITIZATION ID ANGIOTENSIN-II; SEIZURES; AMPHETAMINE; POTENTIATION; SENSITIZATION; LIDOCAINE; BEHAVIOR; AMYGDALA; NUCLEUS; HORMONE AB We report that glucocorticoids significantly facilitated the development of cocaine-induced kindled seizures. These results suggest that glucocorticoids may have effects on the development of kindled seizures which are similar to those of the neuropeptide, corticotropin-releasing hormone (CRH), with which they show a close functional relationship. These results may be of interest in the light of data showing that glucocorticoids increase CRH expression in the central nucleus of the amygdala, which is an important site for the development of kindling. C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. RP KLING, MA (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,NIH BLDG 10,ROOM 3S-231,BETHESDA,MD 20892, USA. RI Kling, Mitchel/F-4152-2010; OI Kling, Mitchel/0000-0002-2232-1409; Demas, Jay/0000-0001-7678-1905 NR 28 TC 29 Z9 29 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 NOV 26 PY 1993 VL 629 IS 1 BP 163 EP 166 DI 10.1016/0006-8993(93)90497-B PG 4 WC Neurosciences SC Neurosciences & Neurology GA MH057 UT WOS:A1993MH05700025 PM 8287272 ER PT J AU SALVADORI, S BRYANT, SD BIANCHI, C BALBONI, G SCARANARI, V ATTILA, M LAZARUS, LH AF SALVADORI, S BRYANT, SD BIANCHI, C BALBONI, G SCARANARI, V ATTILA, M LAZARUS, LH TI PHE(3)-SUBSTITUTED ANALOGS OF DELTORPHIN-C - SPATIAL CONFORMATION AND TOPOGRAPHY OF THE AROMATIC RING IN PEPTIDE RECOGNITION BY DELTA-OPIOID RECEPTORS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID HIGH-AFFINITY; AMPHIBIAN SKIN; SELECTIVE DERMORPHIN; RAT-BRAIN; REQUIREMENTS; SEQUENCE; DERMENKEPHALIN; MORPHINE; FEATURES; RESIDUE AB In order to study the contribution of the electronic, hydrophobic, and conformational properties of the amino acid residue at position 3 in deltorphin C on binding to delta and mu opioid receptors, a series of 5- and 6-membered ring and bicyclic amino acid replacements at position 3 were prepared by solution synthesis methods. In general, the substitutions were deleterious for high delta affinity (K-i(delta)) and delta selectivity (K-i(mu)/K-i(delta)). However, several notable exceptions were recognized: peptides containing the constrained, bicyclic structures Aic(3) and (R or S) Atc(3) enhanced delta affinity, but only the latter increased delta selectivity 4-fold (=2475) relative to deltorphin C(=661); at the other extreme, delta affinity of N(a)MePh(3) fell 900-fold. Bioassays of [N(a)MePhe(3)]-, [(R or S)C(a)MePhe(3)]-, [Tic(3)]-, [Aic(3)]-, and [(R or S) Atc(3)]deltorphin C using guinea pig ileum (GPI) and mouse vas deferens (MVD) for mu and delta bioactivity, respectively, revealed a significant correlation (r=0.916) between MVD bioactivity and delta binding in brain membranes. [(R or S)Atc(3)]deltorphin C also exhibited the highest biological selectivity (GPI/MVD) (=3,522), which was 3-fold greater than that observed for deltorphin C. Molecular modelling of [N(a)MePhe(3)]- and [(S)Atc(3)]deltorphin C established that these amino acid replacements for Phe(3) produce alterations in the backbone (phi,psi) and side-chain ((chi)1,(chi)2) dihedrals which critically affect the flexibility of the peptide and possibly limit accessible conformations for its alignment within the delta opioid receptor. The data provide evidence that the delta receptor is sensitive to changes in the composition, conformation, and orientation of the side chain of residue 3 of a linear opioid heptapeptide. C1 NIEHS,INTEGRAT BIOL LAB,PEPTIDE NEUROCHEM SECT,RES TRIANGLE PK,NC 27709. UNIV FERRARA,DEPT PHARMACEUT SCI,I-44100 FERRARA,ITALY. UNIV HELSINKI,DEPT PHARM,DIV PHARMACOL & TOXICOL,HELSINKI,FINLAND. OI SALVADORI, Severo/0000-0002-8224-2358 NR 56 TC 44 Z9 44 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 26 PY 1993 VL 36 IS 24 BP 3748 EP 3756 DI 10.1021/jm00076a001 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA ML007 UT WOS:A1993ML00700002 PM 8254604 ER PT J AU FISCHER, B BOYER, JL HOYLE, CHV ZIGANSHIN, AU BRIZZOLARA, AL KNIGHT, GE ZIMMET, J BURNSTOCK, G HARDEN, TK JACOBSON, KA AF FISCHER, B BOYER, JL HOYLE, CHV ZIGANSHIN, AU BRIZZOLARA, AL KNIGHT, GE ZIMMET, J BURNSTOCK, G HARDEN, TK JACOBSON, KA TI IDENTIFICATION OF POTENT, SELECTIVE P-2Y-PURINOCEPTOR AGONISTS - STRUCTURE-ACTIVITY-RELATIONSHIPS FOR 2-THIOETHER DERIVATIVES OF ADENOSINE 5'-TRIPHOSPHATE SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PIG TAENIA-COLI; PHOSPHOLIPASE-C; RECEPTOR; ATP; P2-PURINOCEPTORS; P2Y-PURINOCEPTOR; P1-PURINOCEPTOR; PHARMACOLOGY; ACTIVATION; RESPONSES AB Study of P-2-purinoceptor subtypes has been difficult due to the lack of potent and selective ligands. With the goal of developing high affinity P-2-purinoceptor-selective agonists, we have synthesized a series of analogues of adenine nucleotides modified on the purine ring as chain-extended 2-thioethers or as N-6-methyl-substituted compounds. Chemical functionality incorporated in the thioether moiety included cyanoalkyl, nitroaromatic, amino, thiol, cycloalkyl, n-alkyl, and olefinic groups. Apparent affinity of the compounds for P-2Y-purinoceptors was established by measurement of P-2Y-purinoceptor-promoted phospholipase C activity in turkey erythrocyte membranes and relaxation of carbachol-contracted smooth muscle in three different preparations (guinea pig taenia coli, rabbit aorta, and rabbit mesenteric artery). Activity at P-2X-purinoceptors was established by measurement of contraction of rabbit saphenous artery and of the guinea pig vas deferens and urinary bladder. All 11 of the 2-thioethers of ATP stimulated the production of inositol phosphates with K-0.5 values of 1.5-770 nM, with an (aminophenyl)ethyl derivative being most potent. Two adenosine diphosphate analogues were equipotent to the corresponding ATP analogues. Adenosine monophosphate analogues were full agonists, although generally 4 orders of magnitude less potent. ATP 2-thioethers displayed pD(2) values in the range of 6-8 in smooth muscle assay systems for activity at P-2Y-receptors. There was a significant correlation for the 2-thioether compounds between the pK(0.5) values for inositol phosphate production and the pD(2) values for relaxation mediated via the P-2Y-purinoceptors in the guinea pig taenia coli, but not for the vascular P-2Y-receptors or for the P-2X-receptors. At P-2X-receptors, no activity was observed in the rabbit saphenous artery, but variable degrees of activity were observed in the guinea pig vas deferens and bladder depending on distal substituents of the thioether moiety. N-6-Methyl-ATP was inactive at P-2X-receptors, and approximately equipotent to ATP at taenia coli P-2Y-receptors. This suggested that hybrid N-6-methyl and 2-thioether ATP derivatives might be potent and selective for certain P-2Y-receptors, as was shown for one such derivative, N-6-methyl-2-(5-hexenylthio)-ATP. C1 NIDDK, MOLEC RECOGNIT SECT, BIOORGAN CHEM LAB, BETHESDA, MD 20892 USA. UNIV N CAROLINA, SCH MED, DEPT PHARMACOL, CHAPEL HILL, NC 27599 USA. UCL, DEPT ANAT, LONDON WC1E 6BT, ENGLAND. UCL, LONDON, ENGLAND. KAZAN MED INST, KAZAN 420012, RUSSIA. RI Jacobson, Kenneth/A-1530-2009; OI Jacobson, Kenneth/0000-0001-8104-1493; Ziganshin, Ayrat/0000-0002-9087-7927 FU Intramural NIH HHS [Z01 DK031116-20, Z99 DK999999]; NIGMS NIH HHS [GM38213, GM29536, R01 GM038213]; Wellcome Trust NR 38 TC 90 Z9 92 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 26 PY 1993 VL 36 IS 24 BP 3937 EP 3946 DI 10.1021/jm00076a023 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA ML007 UT WOS:A1993ML00700024 PM 8254622 ER PT J AU CHEN, GT KING, M GUSOVSKY, F CREVELING, CR DALY, JW CHEN, BH NIE, JY KIRK, KL AF CHEN, GT KING, M GUSOVSKY, F CREVELING, CR DALY, JW CHEN, BH NIE, JY KIRK, KL TI SYNTHESES OF 2,5-DIFLUORONOREPINEPHRINE, 2,6-DIFLUORONOREPINEPHRINE, 2,5-DIFLUOROEPINEPHRINE, AND 2,6-DIFLUOROPHENYLEPHRINE - EFFECT OF DISUBSTITUTION WITH FLUORINE ON ADRENERGIC ACTIVITY SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID AGONIST; SUBSTITUTION; RECEPTORS; BINDING; AGENTS AB Synthetic routes to difluorinated analogs of the adrenergic agonists, norepinephrine (NE), epinephrine (E), and phenylephrine (PE) have been developed. The syntheses were based on elaboration of the ethanolamine side chains from the appropriately polyfunctionalized benzaldehydes, The benzaldehydes were prepared from precursor difluorinated benzenes by sequential regioselective lithiations and reaction with electrophiles to introduce hydroxyl and carboxaldehyde functionalities. Binding and functional assay data demonstrate that the 2,6-difluorinated analogs are relatively inactive at both alpha- and beta-adrenergic receptors. These results are consistent with earlier observations that 2-fluoro substitution of adrenergic agonists decreases alpha-adrenergic activity whereas 6-fluoro substitution decreases beta-adrenergic activity. C1 NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,DEPT CHEM,WASHINGTON,DC 20052. NR 23 TC 12 Z9 12 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD NOV 26 PY 1993 VL 36 IS 24 BP 3947 EP 3955 DI 10.1021/jm00076a024 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA ML007 UT WOS:A1993ML00700025 PM 8254623 ER PT J AU REN, K DUBNER, R AF REN, K DUBNER, R TI NMDA RECEPTOR ANTAGONISTS ATTENUATE MECHANICAL HYPERALGESIA IN RATS WITH UNILATERAL INFLAMMATION OF THE HINDPAW SO NEUROSCIENCE LETTERS LA English DT Article DE MECHANICAL HYPERALGESIA; COMPLETE FREUNDS ADJUVANT; VON FREY FILAMENT; MK-801; AP-5 ID BEHAVIORAL HYPERALGESIA; NOXIOUS-STIMULATION; CENTRAL COMPONENT; SPINAL-CORD; NEURONS; MODEL; PAIN; ARTHRITIS; INJURY; INVOLVEMENT AB The effects of N-methyl-D-aspartate (NMDA) receptor antagonists on mechanical hyperalgesia associated with tissue inflammation were studied. Following an injection of the inflammatory agent, complete Freund's adjuvant, into the rat hindpaw, there was a significant decrease in threshold and an increase in response duration to mechanical stimuli, suggesting that a state of mechanical hyperalgesia was induced. The intrathecal administration of the NMDA receptor antagonists, dizocilpine maleate and (+/-)-2-amino-5-phosphonopentanoic acid, significantly increased mechanical threshold and reduced response duration in the inflamed hindpaw, but had no effect on the non-injected paw. The results suggest that NMDA receptor activation may contribute to the mechanical hyperalgesia that follows peripheral tissue inflammation. RP REN, K (reprint author), NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BLDG 49,ROOM 1A-11,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 30 TC 143 Z9 144 U1 0 U2 4 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 NOV 26 PY 1993 VL 163 IS 1 BP 22 EP 26 DI 10.1016/0304-3940(93)90220-F PG 5 WC Neurosciences SC Neurosciences & Neurology GA MH360 UT WOS:A1993MH36000007 PM 7905196 ER PT J AU SUNAGA, K CHUANG, DM ISHITANI, R AF SUNAGA, K CHUANG, DM ISHITANI, R TI TETRAHYDROAMINOACRIDINE INCREASES M(3)-, BUT NOT M(2)-, MUSCARINIC ACETYLCHOLINE-RECEPTOR MESSENGER-RNA LEVELS IN DIFFERENTIATING CEREBELLAR GRANULE CELLS SO NEUROSCIENCE LETTERS LA English DT Article DE TETRAHYDROAMINOACRIDINE; ALZHEIMERS DISEASE; ANTIDEMENTIA; CEREBELLAR GRANULE CELL; NEUROTROPHIC FACTOR; MUSCARINIC ACETYLCHOLINE RECEPTOR; NORTHERN BLOTTING ID ALZHEIMERS-DISEASE; PRECURSOR; SUBTYPES; CULTURE; PROTEIN; RELEASE AB We used Northern blot hybridization to determine whether 9-amino-1,2,3,4-tetrahydroacridine (THA), a potential antidementia drug, selectively altered the levels of muscarinic acetylcholine receptor (mAChR) mRNA in differentiating cerebellar granule cells. Granule cells were cultured for 8 days in media containing 15 mM K+, 25 mM K+ or 15 mM K+ plus 30 mu M THA. High K+ markedly increased the levels of m(2)- and m(3)-mAChR mRNA in the surviving cells. In contrast, THA increased the levels of m(3)-mAChR mRNA, but had little or no effect on m(2)-mAChR mRNA levels. These results suggest that THA selectively up-regulates the synthesis of m(3)-mAChR mRNA. C1 JOSAI UNIV,CELLULAR NEUROPHARMACOL GRP,SAKADO,SAITAMA 35002,JAPAN. NIMH,BIOL PSYCHIAT BRANCH,MOLEC NEUROBIOL SECT,BETHESDA,MD 20892. NR 19 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV 26 PY 1993 VL 163 IS 1 BP 27 EP 30 DI 10.1016/0304-3940(93)90221-6 PG 4 WC Neurosciences SC Neurosciences & Neurology GA MH360 UT WOS:A1993MH36000008 PM 8295727 ER PT J AU GRUNWALD, F CRANE, A MENDE, M SUDA, S KENNEDY, C PETTIGREW, KD BIERSACK, HJ SOKOLOFF, L KUSCHINSKY, W AF GRUNWALD, F CRANE, A MENDE, M SUDA, S KENNEDY, C PETTIGREW, KD BIERSACK, HJ SOKOLOFF, L KUSCHINSKY, W TI EFFECTS OF PHYSOSTIGMINE ON LOCAL CEREBRAL GLUCOSE-UTILIZATION IN THE CENTRAL COMPONENTS OF THE RAT VISUAL-SYSTEM SO NEUROSCIENCE LETTERS LA English DT Article DE PHYSOSTIGMINE; 2-DEOXYGLUCOSE; VISUAL SYSTEM; CHOLINERGIC SYSTEM; ENUCLEATION; RAT BRAIN; AUTORADIOGRAPHY ID BRAIN; NICOTINE AB The effects of intravenous administration of physostigmine at doses of 0.03, 0.095, or 0.3 mg/kg on local cerebral glucose utilization (LCGU) were determined in 3 structures of the visual system of the rat brain by means of the quantitative 2-[C-14]deoxyglucose method. LCGU was increased in the superior colliculus (superficial gray layer), but unchanged in the visual cortex and the lateral geniculate body. To determine whether the observed effect of physostigmine on the superior colliculus depended on input from the retina, the highest dose of physostigmine was administered to rats which had previously been enucleated bilaterally. Enucleation decreased LCGU in the superior colliculus of the animals not treated with physostigmine and blocked the effect of physostigmine on LCGU. The effect of physostigmine in the superior colliculus appears, therefore, to depend on input from the retina. C1 UNIV BONN,DEPT PHYSIOL,W-5300 BONN,GERMANY. UNIV HEIDELBERG,DEPT PHYSIOL,HEIDELBERG,GERMANY. NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. NIMH,DIV BIOMETRY & APPL SCI,BETHESDA,MD 20892. RP GRUNWALD, F (reprint author), UNIV BONN,DEPT NUCL MED,W-5300 BONN,GERMANY. NR 20 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 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV 26 PY 1993 VL 163 IS 1 BP 67 EP 70 DI 10.1016/0304-3940(93)90230-I PG 4 WC Neurosciences SC Neurosciences & Neurology GA MH360 UT WOS:A1993MH36000017 PM 8295735 ER PT J AU MEZEY, E PALKOVITS, M AF MEZEY, E PALKOVITS, M TI ACTIONS OF ANTIULCER DRUGS - RESPONSE SO SCIENCE LA English DT Article C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NINCDS,BETHESDA,MD 20892. RP MEZEY, E (reprint author), SEMMELWEIS UNIV MED,NEUROMORPHOL LAB,H-1085 BUDAPEST 8,HUNGARY. RI Palkovits, Miklos/F-2707-2013 NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 26 PY 1993 VL 262 IS 5138 BP 1454 EP 1455 DI 10.1126/science.262.5138.1454-a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MJ046 UT WOS:A1993MJ04600045 ER PT J AU HIRATA, Y KIUCHI, K CHEN, HC MILBRANDT, J GUROFF, G AF HIRATA, Y KIUCHI, K CHEN, HC MILBRANDT, J GUROFF, G TI THE PHOSPHORYLATION AND DNA-BINDING OF THE DNA-BINDING DOMAIN OF THE ORPHAN NUCLEAR RECEPTOR NGFI-B SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NERVE GROWTH-FACTOR; CASEIN KINASE-II; CHROMAFFIN CELLS; FIBER OUTGROWTH; PROTEIN; GENE; TRANSCRIPTION; MEMBER; SUPERFAMILY; NEURONS AB NGFI-B is an orphan member of the nuclear receptor superfamily encoded by an immediate-early gene. It is rapidly synthesized and phosphorylated in PC12 cells in response to nerve growth factor (NGF) and other agents and is differentially phosphorylated dependent upon the inducing stimulus. The DNA-binding domain (DBD) of NGFI-B has been expressed in bacteria and purified. The purified protein is phosphorylated by protein kinase A or by extracts from NGF-treated PC12 cells. The phosphorylated residues within the DBD have been identified as Ser-340 and Ser-350. The use of mutants in which either or both of these residues were replaced with alanines revealed that phosphorylation of Ser-350, located within the ''A box,'' a motif necessary for DNA binding by NGFI-B, resulted in a decrease in binding to the NGFI-B response element, while phosphorylation of Ser-340 had little or no effect. These findings demonstrate that phosphorylation of a nuclear receptor DBD results in a change in DNA binding and provides another potential mechanism for regulating NGFI-B activity. C1 NICHHD,GROWTH FACTORS SECT,BLDG 49,RM 5A64,BETHESDA,MD 20892. WASHINGTON UNIV,SCH MED,DEPT PATHOL,DIV LAB MED,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT INTERNAL MED,DIV LAB MED,ST LOUIS,MO 63110. NR 36 TC 91 Z9 93 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1993 VL 268 IS 33 BP 24808 EP 24812 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MG673 UT WOS:A1993MG67300045 PM 8227042 ER PT J AU LEAMON, CP PASTAN, I LOW, PS AF LEAMON, CP PASTAN, I LOW, PS TI CYTOTOXICITY OF FOLATE-PSEUDOMONAS EXOTOXIN CONJUGATES TOWARD TUMOR-CELLS - CONTRIBUTION OF TRANSLOCATION DOMAIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BINDING-PROTEIN; GLYCOSYL-PHOSPHATIDYLINOSITOL; RECOMBINANT FORM; RECEPTOR; MEMBRANE; CYTOSOL; TRANSPORT; CLEAVAGE; FRAGMENT; ABRIN AB Folate-protein conjugates can be nondestructively delivered into a cell's cytoplasm via folate receptor-mediated endocytosis if (i) the target cells express a folate-binding protein, and (ii) if the folate is linked to its attached protein at a site that does not interfere with receptor recognition. Because such conjugates have been observed to remain in endosomal compartments for extended periods following cellular uptake, we decided to evaluate whether release into the cytoplasm might be expedited by inclusion of a translocation domain in the folate-protein construct. To test this possibility, momordin-folate and truncated Pseudomonas exotoxin-folate conjugates (LysPE38 and CysPE35), i.e. protein synthesis inhibitors either lacking or containing the desired translocation domain, respectively, were examined for their abilities to block protein synthesis in a variety of cell types. The translocation competent LysPE38-folate construct was found to kill cells six times more rapidly with 10-fold greater potency than the permeation-incompetent momordin-folate. Further, cells expressing low levels of folate receptors could only be exterminated by the translocation competent Pseudomonas exotoxin-folate conjugates. When the translocation capability of CysPE35-folate was inactivated by modification of Cys287, the construct also lost most of its cytotoxicity. These data suggest that autocatalysis of transport from an internal vesicular compartment into the cytoplasm can greatly augment the cytotoxicity of a protein toxin entering cells via the folate endocytosis pathway. Because the folate ligand can selectively target a protein conjugate to cancer cells in the presence of normal cells, such translocatable toxin-folate constructs warrant further study as a possible treatment for some malignancies. C1 PURDUE UNIV, DEPT CHEM, W LAFAYETTE, IN 47907 USA. GLAXO RES INST, DEPT OLIGOMER DEV, RES TRIANGLE PK, NC 27709 USA. NCI, DEPT MOLEC BIOL, BETHESDA, MD 20892 USA. OI Low, Philip/0000-0001-9042-5528 NR 31 TC 148 Z9 154 U1 0 U2 4 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 NOV 25 PY 1993 VL 268 IS 33 BP 24847 EP 24854 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MG673 UT WOS:A1993MG67300051 PM 8227046 ER PT J AU BOISCLAIR, YR BROWN, AL CASOLA, S RECHLER, MM AF BOISCLAIR, YR BROWN, AL CASOLA, S RECHLER, MM TI 3 CLUSTERED SP1 SITES ARE REQUIRED FOR EFFICIENT TRANSCRIPTION OF THE TATA-LESS PROMOTER OF THE GENE FOR INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-2 FROM THE RAT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID POLYMERASE-II TRANSCRIPTION; ACTIVATOR INHIBITOR-1 GENE; RECEPTOR GENE; SYNERGISTIC ACTIVATION; IGF-I; EXPRESSION; BOX; SEQUENCE; DNA; CLONING AB Insulin-like growth factor-binding protein-2 (IGFBP-2) transcription in rat liver varies with developmental age and fasting. To define the DNA elements required for efficient expression of the TATA-less rat IGFBP-2 gene, the native or mutated promoter was fused to a promoterless luciferase reporter gene and transfected into BRL-3A rat liver and 293 human embryonic kidney cell lines. Luciferase activity decreased approximately 25-fold with progressive 5' promoter deletions from nucleotide (nt) -581 to nt -189 (relative to ATG, +1). The smallest construct, however, still had >21-fold greater luciferase activity than the promoterless construct. In DNase I footprinting assays using native nt -276 to -36 promoter fragments or fragments containing block substitution mutations, BRL-3A nuclear extract and purified human transcription factor Sp1 protected a region from nt -234 to -215 containing one GC box and a broad region from nt -189 to -125 that contained three clustered but independent GC boxes. In gel retardation assays using an Spl oligonucleotide probe, BRL-3A extract formed two closely migrating complexes that were immunologically related to Spl; Spl gave a single complex that co-migrated with the more retarded BRL-3A complex. Binding was competitively inhibited by oligonucleotides corresponding to each of the four GC boxes. The proximal three GC boxes were sufficient to allow trans-activation of the IGFBP-2 promoter by Spl in Drosophila SL2 cells. Independent block mutations indicated that all three of the GC boxes are required for promoter activity and are equally important. Thus, binding of Spl or Sp1-related proteins to three clustered GC boxes in the proximal IGFBP-2 promoter is essential for promoter activity. Multiple upstream regions also contribute to the full expression of the IGFBP-2 gene. RP BOISCLAIR, YR (reprint author), NIDDKD,MOLEC & CELLULAR ENDOCRINOL BRANCH,GROWTH & DEV SECT,BLDG 10,RM 8D-14,BETHESDA,MD 20892, USA. NR 62 TC 115 Z9 117 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 NOV 25 PY 1993 VL 268 IS 33 BP 24892 EP 24901 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MG673 UT WOS:A1993MG67300058 PM 7693708 ER PT J AU STEINERT, PM MAREKOV, LN PARRY, DAD AF STEINERT, PM MAREKOV, LN PARRY, DAD TI DIVERSITY OF INTERMEDIATE FILAMENT STRUCTURE - EVIDENCE THAT THE ALIGNMENT OF COILED-COIL MOLECULES IN VIMENTIN IS DIFFERENT FROM THAT IN KERATIN INTERMEDIATE FILAMENTS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NEUROFILAMENT-L PROTEIN; INVITRO; CELLS; ARCHITECTURE; HETERODIMER; EXPRESSION; COMPLEXES; REGISTER; SUBUNITS AB Although vimentin intermediate filaments (IF) are morphologically similar to all other IF types, cells have evolved different ways of manipulating vimentin and keratin IF. The structural basis for such differences is unknown. We have explored this by use of cross-linking experiments on vimentin oligomers, polymers, and intact IF to determine the axial length of vimentin molecules and the degrees to which neighboring molecules are aligned in IF. Our data reveal that the homodimer vimentin molecule (43.9 nm) is clearly shorter than a keratin heterodimer molecule (46.2 nm). Vimentin assemblies contain three modes of antiparallel molecular alignments: A11 and A22 in two-molecule or larger oligomeric assemblies, in which the two molecules are staggered so as to bring their 1B and 2B rod domain segments, respectively, into register; and A12 in higher order molecular assemblies in which the two neighboring molecules are largely overlapped. Since the repeat axial length of the vimentin assemblies (42.6 nm) is less than the molecular length, this means there is an overlap (designated as alignment A(CN)) of about 1 nm (5-10 residues) between the end of the 2B and beginning of the IA rod domain segments of similarly directed molecules in the IF. Interestingly, these four modes of nearest neighbor molecular alignments also occur in keratin IF. However, the degree of stagger of alignments in the A11 and A22 modes is different (staggers of -19.5 for vimentin versus -16.6 nm for keratin, and 23.3 and 28.6 nm, respectively). Two-dimensional surface lattice maps of the two IF types are very similar, except for differences in molecule alignments and different axial repeats of 21.4 nm in vimentin and 22.6 nm in keratin IF. Although vimentin-keratin hybrid molecules can be induced to form in vitro, they do not assemble into higher order structures. The data suggest that vimentin and keratin are incapable of assembly into IF in vitro or in vivo simply because their molecules are of different axial lengths and because the exact axial alignments of neighboring molecules are different. C1 MASSEY UNIV,DEPT PHYS & BIOPHYS,PALMERSTON NORTH,NEW ZEALAND. RP STEINERT, PM (reprint author), NIAMSD,SKIN BIOL BRANCH,BLDG 6,RM 425,BETHESDA,MD 20892, USA. NR 45 TC 123 Z9 124 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 1993 VL 268 IS 33 BP 24916 EP 24925 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MG673 UT WOS:A1993MG67300061 PM 7693709 ER PT J AU JEANG, KT BERKHOUT, B DROPULIC, B AF JEANG, KT BERKHOUT, B DROPULIC, B TI EFFECTS OF INTEGRATION AND REPLICATION ON TRANSCRIPTION OF THE HIV-1 LONG TERMINAL REPEAT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TAT PROTEIN; TRANS-ACTIVATION; PROCESSIVITY FACTOR; MUTATIONAL ANALYSIS; INDUCED EXPRESSION; NASCENT RNA; TRANSACTIVATION; TYPE-1; PROMOTER AB The activity of a promoter is influenced by chromosomal and cell cycle/replication context. We analyzed the influences of integration and replication on transcription of the human immunodeficiency virus (HIV)-1 long terminal repeat (LTR). We found that one requirement for Tat trans-activated expression differed for integrated versus unintegrated HIV-1 LTR. Specifically, the second coding exon of Tat, previously regarded as functionally dispensable, plays a role in the optimal activation of integrated LTRs. We also found that the transcription profile produced from the HIV-1 LTR is influenced by replication. Autonomously replicating vectors that contain the HIV-1 LTR produced patterns of transcription different from counterpart vectors that do not replicate. Both replicating and nonreplicating HIV-1 LTRs remained responsive to Tat. RP JEANG, KT (reprint author), NIAID,MOLEC VIROL SECT,MOLEC MICROBIOL LAB,BETHESDA,MD 20892, USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 56 TC 71 Z9 71 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 NOV 25 PY 1993 VL 268 IS 33 BP 24940 EP 24949 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MG673 UT WOS:A1993MG67300064 PM 8227056 ER PT J AU WANG, Q ORRISON, BM MARINI, JC AF WANG, Q ORRISON, BM MARINI, JC TI 2 ADDITIONAL CASES OF OSTEOGENESIS IMPERFECTA WITH SUBSTITUTIONS FOR GLYCINE IN THE ALPHA-2(I) COLLAGEN CHAIN - A REGIONAL MODEL RELATING MUTATION LOCATION WITH PHENOTYPE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID I PROCOLLAGEN; POINT MUTATIONS; TRIPLE HELIX; COL1A1; VALINE; GENE; FEATURES AB The relationship between the clinical severity of osteogenesis imperfecta (OI) and the location and type of amino acid substitution in type I collagen is not identical for mutations in the alpha1(I) and alpha2(I) chains. Furthermore, the alpha2(I) chain, once thought to be associated with moderate forms of OI, has now been associated with approximately as many lethal as non-lethal cases. We describe two novel substitutions for glycine in the alpha2(I) chain, one associated with a lethal phenotype in twins and the other with a moderate non-lethal phenotype. The type I collagen of all probands was characterized electrophoretically by two populations of alpha chains, one normal and one with delayed migration. Cyanogen bromide peptides of the overmodified alpha1(I) chains revealed delayed migration of all peptides except CB6. The indicated target region of alpha1(I) and alpha2(I) cDNA of the probands was analyzed by RNA-DNA hybrid analysis with RNase A digestion. All probands had mismatches in the region of alpha2(I) coding for amino acids 642-912. The lethal phenotype was associated with a G --> A mutation, resulting in Gly706 --> serine; the non-lethal mutation was a G --> T change resulting in Gly676 --> valine. Both mutations occurred de novo in the probands; parental leukocyte DNA was normal. In conjunction with the previously described exon deletions and point mutations in alpha2(I), these mutations define five alternating non-lethal/lethal regions along the chain and support a regional, as opposed to a gradient, model of OI pathophysiology. These mutations in particular help to define a lethal/non-lethal junction at about alpha2(I) amino acid 700. C1 NICHHD,HUMAN GENET BRANCH,CONNECT TISSUE DISORDERS SECT,BLDG 10,RM 95242,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 20 TC 32 Z9 34 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 NOV 25 PY 1993 VL 268 IS 33 BP 25162 EP 25167 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MG673 UT WOS:A1993MG67300092 PM 7693712 ER PT J AU KOONIN, EV RUDD, KE AF KOONIN, EV RUDD, KE TI SPOU PROTEIN OF ESCHERICHIA-COLI BELONGS TO A NEW FAMILY OF PUTATIVE RIBOSOMAL-RNA METHYLASES SO NUCLEIC ACIDS RESEARCH LA English DT Note ID ALIGNMENT RP NIH, NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20894 USA. NR 8 TC 25 Z9 30 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 25 PY 1993 VL 21 IS 23 BP 5519 EP 5519 DI 10.1093/nar/21.23.5519 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MK397 UT WOS:A1993MK39700037 PM 8265370 ER PT J AU YOO, SH AF YOO, SH TI PH-DEPENDENT BINDING OF CHROMOGRANIN-B AND SECRETORY VESICLE MATRIX PROTEINS TO THE VESICLE MEMBRANE SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE CHROMOGRANIN-B; PH-DEPENDENT BINDING; SECRETORY VESICLE; MATRIX PROTEIN; VESICLE MEMBRANE ID ADRENAL CHROMAFFIN GRANULES; SECRETOGRANIN-I; MESSENGER-RNA; CDNA SEQUENCE; CALCIUM; CELLS; AGGREGATION; ENDOCRINE; TISSUE; PANCREASTATIN AB Contrary to the notion that the soluble intravesicular matrix proteins of the secretory vesicles of adrenal medullary chromaffin cells freely float in the vesicle, several vesicle matrix proteins of the secretory vesicles, including chromagranins A and B, bound to the vesicle membrane at intravesicular pH (5.5) and were freed from it when the pH was raised to a near physiological pH (7.5). Estimation of the fraction of vesicle matrix proteins that might remain bound to the vesicle membrane in the vesicle suggested that the majority (> 50-80%) of chromogranins A and B. as well as several other proteins, will stay bound to the membrane in the vesicle. Comparison of the amino-acid sequences of chromogranins A and B revealed two highly conserved regions, i.e., one near the N-terminus and the other being the C-terminal region. Since it has been demonstrated with chromogranin A that the conserved near N-terminal region of chromogranin A exhibited the pH-dependent membrane-binding activity (Yoo, S.H. (1993) Biophys. J., 64, A195), the same region in chromogranin B (residues 17-36) was tested using a synthetic chromogranin B peptide, and found to exhibit the pH-dependent membrane-binding activity. The pH-dependent binding of the matrix proteins at pH 5.5 and the automatic untethering at a physiological pH accord well with the rapid release and circulation of the vesicular contents in the bloodstream. RP YOO, SH (reprint author), NIDOCD,CELLULAR BIOL LAB,BLDG 36,ROOM 5D-15,BETHESDA,MD 20892, USA. NR 50 TC 24 Z9 25 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 NOV 24 PY 1993 VL 1179 IS 3 BP 239 EP 246 DI 10.1016/0167-4889(93)90078-4 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MJ882 UT WOS:A1993MJ88200001 PM 8218367 ER PT J AU SORLIE, PD BACKLUND, E JOHNSON, NJ ROGOT, E AF SORLIE, PD BACKLUND, E JOHNSON, NJ ROGOT, E TI MORTALITY BY HISPANIC STATUS IN THE UNITED-STATES SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID NATIONAL-DEATH-INDEX; NUTRITION-EXAMINATION-SURVEY; ISCHEMIC HEART-DISEASE; MEXICAN-AMERICANS; CIGARETTE-SMOKING; RISK-FACTORS; HEALTH; WHITES; HHANES; HYPERTENSION AB Objective.-To compare all-cause and cause-specific mortality rates between Hispanic and non-Hispanic groups and estimate the effect of family income, place of birth, and place of residence on these rates. Design.-Cohort study using national survey data matched to the National Death Index, with a mortality follow-up period of 9 years. Setting.-The noninstitutionalized population of the United States. Participants.-Approximately 700 000 respondents (aged 25 years or older), including 40 000 Hispanics, to national surveys conducted by the US Bureau of the Census (Current Population Surveys). Outcome Measures.-All causes and underlying cause of death, coded from the death certificate, occurring between 1979 and 1987. Results.-Adjusting for age, Hispanics were shown to have lower mortality from all causes compared with non-Hispanics (standardized rate ratio [SRR], 0.74 for men, 0.82 for women), lower mortality from cancer (SRR, 0.69 for men, 0.61 for women), lower mortality from cardiovascular disease (SRR, 0.65 for men, 0.80 for women), higher mortality from diabetes (SRR, 1.86 for men, 2.38 for women), and higher mortality from homicide (SRR, 3.60 for men). After adjusting for differences in annual family income, the relative mortality ratios were even lower for Hispanics than non-Hispanics. Conclusions.-These data describe, in a large national cohort study, a lower mortality in Hispanics than in non-Hispanics. This mortality is particularly low after adjustment for differences in family income. C1 BUR CENSUS,SUITLAND,MD. RP SORLIE, PD (reprint author), NHLBI,EPIDEMIOL & BIOMETRY PROGRAM,FED BLDG,ROOM 3A10,BETHESDA,MD 20892, USA. NR 34 TC 272 Z9 274 U1 0 U2 9 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 NOV 24 PY 1993 VL 270 IS 20 BP 2464 EP 2468 DI 10.1001/jama.270.20.2464 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA MG671 UT WOS:A1993MG67100028 PM 8031341 ER PT J AU DUVERGER, N RADER, D DUCHATEAU, P FRUCHART, JC CASTRO, G BREWER, HB AF DUVERGER, N RADER, D DUCHATEAU, P FRUCHART, JC CASTRO, G BREWER, HB TI BIOCHEMICAL-CHARACTERIZATION OF THE 3 MAJOR SUBCLASSES OF LIPOPROTEIN-A-I PREPARATIVELY ISOLATED FROM HUMAN PLASMA SO BIOCHEMISTRY LA English DT Article ID HIGH-DENSITY-LIPOPROTEIN; LECITHIN-CHOLESTEROL ACYLTRANSFERASE; CELL-DERIVED CHOLESTEROL; LIPID TRANSFER PROTEIN; MOUSE ADIPOSE-CELLS; MONOCLONAL-ANTIBODY; GEL-ELECTROPHORESIS; HEPATIC LIPASE; PARTICLES; BINDING AB Apolipoprotein (apo) A-I is the major protein constituent of plasma high-density lipoproteins (HDL). HDL consist of two major classes of apoA-I-containing lipoproteins: LpA-I and LPA-I:A-II. LpA-I includes heterogeneous lipoprotein particles that differ in size and hydrated density. LpA-I was isolated by immunoaffinity chromatography from the fasting plasma of 24 normal human subjects and separated by gel filtration chromatography. Three major subclasses of LpA-I were eluted: large (Lg-LpA-I), medium (Md-LpA-I), and small LpA-I (Sm-LpA-I). By nondenaturing gradient PAGE, Lg-LpA-I, Md-LpA-I, and Sm-LpA-I had mean Stokes diameters of 10.8 +/- 0.5, 8.9 +/- 0.5, and 7.5 +/- 0.3 nm, respectively. The lipid/protein ratios were 1.25 +/- 0.12 for Lg-LpA-I, 0.75 +/- 0.10 for Md-LpA-I, and 0.38 +/- 0.08 for Sm-LpA-I. Lg-LpA-I was relatively lipid and cholesteryl ester rich compared with Md-LpA-I and Sm-LpA-I. Sm-LpA-I contained phospholipids as the major lipid component. ApoA-I was the major apolipoprotein in all LpA-1 subfractions, whereas apoE was present only in Lg-LpA-I and apoA-IV was associated with both Md-LpA-I and Sm-LpA-I. All three LpA-I subclasses exhibited predominantly alpha mobility on agarose electrophoresis. Lg-LpA-I migrated as a diffuse band in the fast alpha position, whereas Md-LpA-I and Sm-LpA-I migrated to the slow alpha position. In addition, both Lg-LpA-I and Sm-LpA-I, but not Md-LpA-I, had components with pre-beta electrophoretic mobility. All three LpA-I subclasses bound specifically to Ob 1771 cells and promoted cholesterol efflux. Lg-LpA-I had a significantly higher amount of LCAT and CETP activity per particle than Md-LpA-I and Sm-LpA-I. These data indicate that these LpA-I subclasses have distinctive size, electrophoretic mobility, composition, and metabolic activities and provide new insights into the molecular architecture of LpA-I and HDL. C1 INST PASTEUR,INSERM,U325,F-59019 LILLE,FRANCE. RP DUVERGER, N (reprint author), NHLBI,MOLEC DIS BRANCH,BLDG 10,ROOM 7N117,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 60 TC 51 Z9 51 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 NOV 23 PY 1993 VL 32 IS 46 BP 12372 EP 12379 DI 10.1021/bi00097a014 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MH746 UT WOS:A1993MH74600014 PM 8241125 ER PT J AU YOO, SH FERRETTI, JA AF YOO, SH FERRETTI, JA TI NATURE OF THE PH-INDUCED CONFORMATIONAL-CHANGES AND EXPOSURE OF THE C-TERMINAL REGION OF CHROMOGRANIN-A SO FEBS LETTERS LA English DT Article DE CHROMOGRANIN-A; CONFORMATION; PH; C-TERMINAL REGION ID SECONDARY STRUCTURE; CIRCULAR-DICHROISM; PROTEINS; CLEAVAGE; SEQUENCE; CELLS; CA2+ AB Chromogranin A is known to undergo pH induced conformational changes, and the difference in conformation is supposed to be responsible for the difference in Ca2+ binding property. To gain insight regarding the overall structure and the nature of pH-induced conformational changes of chromogranin A, limited trypsin digestions were carried out at pH 5.5 and pH 7.5. The resulting fragments were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the amino acid sequences of the tryptic fragments were determined. From these analyses it was shown that the chromogranin A structure consists of an N-terminal compact core region and a rather loosely organized C-terminal region and that the change of pH from 7.5 to 5.5 loosened the overall structure of chromogranin A, exposing the C-terminal region. Since the conserved C-terminal region (residues 407-431) was shown to exist in monomer-dimer and monomer-tetramer equilibria at pH 7.5 and 5.5, respectively, the conformational changes of the region at pH 7.5 and 5.5 were studied by circular dichroism spectroscopy using a synthetic peptide representing the conserved C-terminal region. When the pH was changed from 7.5 to 5.5, the coil structure of the C-terminal peptide decreased with an accompanying increase of alpha-helicity. C1 NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. RP YOO, SH (reprint author), NIDOCD,CELLULAR BIOL LAB,BLDG 36,ROOM 5D-13,BETHESDA,MD 20892, USA. NR 20 TC 9 Z9 11 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 NOV 22 PY 1993 VL 334 IS 3 BP 373 EP 377 DI 10.1016/0014-5793(93)80715-7 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA MH650 UT WOS:A1993MH65000028 PM 8243650 ER PT J AU ASAKURA, T YEO, JH DEMURA, M ITOH, T FUJITO, T IMANARI, M NICHOLSON, LK CROSS, TA AF ASAKURA, T YEO, JH DEMURA, M ITOH, T FUJITO, T IMANARI, M NICHOLSON, LK CROSS, TA TI STRUCTURAL-ANALYSIS OF UNIAXIALLY ALIGNED POLYMERS USING SOLID-STATE N-15 NMR SO MACROMOLECULES LA English DT Note ID MORI SILK FIBROIN; BOMBYX-MORI; CRYSTAL-STRUCTURE; COAT PROTEIN; CONFORMATION; L-GLUTAMATE) C1 TOYO SEIKAN GRP CO,R&D,HODOGAYA KU,YOKOHAMA,KANAGAWA 240,JAPAN. JERSEY CITY MED CTR,JERSEY CITY,NJ 07304. NIDR,BETHESDA,MD 20892. FLORIDA STATE UNIV,DEPT CHEM,TALLAHASSEE,FL 32306. FLORIDA STATE UNIV,NATL HIGH MAGNET FIELD LAB,TALLAHASSEE,FL 32306. RP ASAKURA, T (reprint author), TOKYO UNIV AGR & TECHNOL,FAC TECHNOL,DEPT BIOTECHNOL,NAKAMACHI 2-CHOME,FUCHU,TOKYO 183,JAPAN. RI Demura, Makoto/F-5272-2011; Asakura, Tetsuo/B-9970-2013 NR 23 TC 25 Z9 27 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0024-9297 J9 MACROMOLECULES JI Macromolecules PD NOV 22 PY 1993 VL 26 IS 24 BP 6660 EP 6663 DI 10.1021/ma00076a056 PG 4 WC Polymer Science SC Polymer Science GA MJ864 UT WOS:A1993MJ86400056 ER PT J AU MANROW, RE BERGER, SL AF MANROW, RE BERGER, SL TI GAG TRIPLETS AS SPLICE ACCEPTORS OF LAST RESORT - AN UNUSUAL FORM OF ALTERNATIVE SPLICING IN PROTHYMOSIN-ALPHA PREMESSENGER RNA SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Note DE PROTHYMOSIN-ALPHA; ALTERNATIVE SPLICING; SPLICE ACCEPTOR; MUTAGENESIS; CONSENSUS SPLICING RULES ID AMINO-ACID SEQUENCE; JUNCTION SEQUENCES; MAMMALIAN INTRONS; GENE FAMILY; EXPRESSION; CDNA; SITE; CLONING; CELLS RP MANROW, RE (reprint author), NCI, BIOCHEM LAB, GENES & GENE PROD SECT, BETHESDA, MD 20892 USA. NR 37 TC 17 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD NOV 20 PY 1993 VL 234 IS 2 BP 281 EP 288 DI 10.1006/jmbi.1993.1583 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MG892 UT WOS:A1993MG89200002 PM 7901421 ER PT J AU CLARK, DJ GHIRLANDO, R FELSENFELD, G EISENBERG, H AF CLARK, DJ GHIRLANDO, R FELSENFELD, G EISENBERG, H TI EFFECT OF POSITIVE SUPERCOILING ON DNA COMPACTION BY NUCLEOSOME CORES SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Note DE POSITIVE SUPERCOILS; NEGATIVE SUPERCOILS; NUCLEOSOME CORE; CHROMATIN COMPACTION ID TRANSCRIPTION; POLYMERASE; NETROPSIN; PARTICLE; TEMPLATE C1 NIDDK,MOLEC BIOL LAB,BLDG 5,ROOM 212,BETHESDA,MD 20892. WEIZMANN INST SCI,DEPT STRUCT BIOL,IL-76100 REHOVOT,ISRAEL. RI Ghirlando, Rodolfo/A-8880-2009 NR 26 TC 16 Z9 16 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD NOV 20 PY 1993 VL 234 IS 2 BP 297 EP 301 DI 10.1006/jmbi.1993.1585 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MG892 UT WOS:A1993MG89200004 PM 8230214 ER PT J AU EKBOM, A HSIEH, CC YUEN, J TRICHOPOULOS, D MCLAUGHLIN, J LAN, SJ ADAMI, HO AF EKBOM, A HSIEH, CC YUEN, J TRICHOPOULOS, D MCLAUGHLIN, J LAN, SJ ADAMI, HO TI RISK OF EXTRAHEPATIC BILEDUCT CANCER AFTER CHOLECYSTECTOMY SO LANCET LA English DT Article ID SCLEROSING CHOLANGITIS; ULCERATIVE-COLITIS; CARCINOMA; CHOLANGIOCARCINOMA; CYSTS AB The aetiology of cancer of the extrahepatic bile duct is unknown. Gallstones have been proposed to be a risk factor on the basis of ecological and epidemiological evidence. As gallstones are formed in the gallbladder, the occurrence of extrahepatic bileduct cancer in patients after cholecystectomy is of interest. All patients (62 734) who had had a cholecystectomy during 1965-1983 within the Uppsala Health Care Region, Sweden, were followed up to the end of 1987. Excluding the first year of follow-up, 23 cancers of the extrahepatic bileduct occurred vs 26.3 expected for a standardised incidence ratio (SIR) of 0.88 (95% confidence interval [CI] 0.56-1.31). 10 years or more after operation there was a greater reduction of risk (SIR = 0.27; 95% CI 0.06-0.80). Similar patterns were observed for men and women, and among patients who had undergone cholecystectomy only compared with those who had had their common bileducts explored. To assess surveillance bias the incidence of primary liver cancer was also analysed: SIR = 1.15; 95% CI 0.91-1.44 overall, and 10 years or more after cholecystectomy SIR = 0.98; 95% CI 0.66-1.40. This study shows a reduced risk of extrahepatic bileduct cancer 10 or more years after cholecystectomy, indicating that gallstones may be a cause of this cancer. C1 NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. RP EKBOM, A (reprint author), UNIV HOSP UPPSALA,CANC EPIDEMIOL UNIT,S-75185 UPPSALA,SWEDEN. FU NCI NIH HHS [5RO1CA44683] NR 27 TC 44 Z9 45 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 NOV 20 PY 1993 VL 342 IS 8882 BP 1262 EP 1265 DI 10.1016/0140-6736(93)92359-2 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA MH566 UT WOS:A1993MH56600009 PM 7901583 ER PT J AU ELDEIRY, WS TOKINO, T VELCULESCU, VE LEVY, DB PARSONS, R TRENT, JM LIN, D MERCER, WE KINZLER, KW VOGELSTEIN, B AF ELDEIRY, WS TOKINO, T VELCULESCU, VE LEVY, DB PARSONS, R TRENT, JM LIN, D MERCER, WE KINZLER, KW VOGELSTEIN, B TI WAF1, A POTENTIAL MEDIATOR OF P53 TUMOR SUPPRESSION SO CELL LA English DT Article ID WILD-TYPE P53; DNA-BINDING SITE; CELL-LINE; COLORECTAL CARCINOMAS; ENHANCED EXPRESSION; GENE-EXPRESSION; GROWTH ARREST; PROTEIN; TRANSCRIPTION; CANCER AB The ability of p53 to activate transcription from specific sequences suggests that genes induced by p53 may mediate its biological role as a tumor suppressor. Using a subtractive hybridization approach, we identified a gene, named WAF1, whose induction was associated with wild-type but not mutant p53 gene expression in a human brain tumor cell line. The WAF1 gene was localized to chromosome 6p21.2, and its sequence, structure, and activation by p53 was conserved in rodents. Introduction of WAF1 cDNA suppressed the growth of human brain, lung, and colon tumor cells in culture. Using a yeast enhancer trap, a p53-binding site was identified 2.4 kb upstream of WAF1 coding sequences. The WAF1 promoter, including this p53-binding site, conferred p53-dependent inducibility upon a heterologous reporter gene. These studies define a gene whose expression is directly induced by p53 and that could be an important mediator of p53-dependent tumor growth suppression. C1 JOHNS HOPKINS UNIV,SCH MED,PROGRAM HUMAN GENET & MOLEC BIOL,BALTIMORE,MD 21231. NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892. THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19107. RP ELDEIRY, WS (reprint author), JOHNS HOPKINS UNIV,SCH MED,CTR ONCOL,BALTIMORE,MD 21231, USA. FU NCI NIH HHS [CA-09071, CA-43460] NR 73 TC 6946 Z9 7029 U1 50 U2 346 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD NOV 19 PY 1993 VL 75 IS 4 BP 817 EP 825 DI 10.1016/0092-8674(93)90500-P PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MH749 UT WOS:A1993MH74900025 PM 8242752 ER PT J AU LIN, PX FIELDS, RD VONAGOSTON, D AF LIN, PX FIELDS, RD VONAGOSTON, D TI EFFECTS OF ELECTRICAL-STIMULATION ON GAP-43 EXPRESSION IN MOUSE SENSORY NEURONS SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE GAP-43; B-50; NEUROMODULIN; SYNAPTIC PLASTICITY; GROWTH CONE; AXON OUTGROWTH; ACTIVITY-DEPENDENT EXPRESSION ID GROWTH-ASSOCIATED PROTEIN; KINASE-C SUBSTRATE; CALMODULIN-BINDING-PROTEIN; BRAIN POLYPHOSPHOINOSITIDE METABOLISM; ROOT GANGLION NEURONS; ADULT-RAT BRAIN; NERVE GROWTH; B-50 GAP-43; NEURITE OUTGROWTH; CEREBRAL-CORTEX AB Effects of electrical activity on GAP-43 expression were tested in mouse dorsal root ganglion (DRG) neurons subjected to electrical stimulation in culture. Patterned electrical stimulation was provided through extracellular electrodes placed in multicompartment cell culture chambers. Stimulation was delivered at 10 Hz, in 0.5 s bursts every 2 s for up to 3 days. Expression of GAP-43 was assessed by immunocytochemistry, two ELISA methods, and Northern blot analysis within three experimental protocols: (1) prior to synaptogenesis, (2) after synaptogenesis with spinal cord neurons, and (3) within the context of activity-dependent synaptic competition, in which synapses from active and inactive DRG neurons converge on the same postsynaptic neurons. None of the stimulation treatments produced a measurable change in GAP-43 or RNA message for the protein, although this electrical stimulus induces persistent changes in synaptic strength, and alters neurite outgrowth in these cultures. The decline in GAP-43 levels between 1 and 3 weeks in culture, which has been reported in other studies, was readily detectable by our measurements. We conclude that regulation of GAP-43 expression is not required for activity-dependent regulation of growth cone motility, synaptogenesis and synapse elimination, or changes in synaptic strength. Instead, post-translational modification, such as phosphorylation, may be the primary means of regulating any GAP-43 functions associated with these activity-dependent processes. C1 NICHHD, DEV NEUROBIOL LAB, BLDG 49, ROOM 5A38, BETHESDA, MD 20892 USA. NR 95 TC 8 Z9 8 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 NOV 19 PY 1993 VL 76 IS 1 BP 95 EP 103 PG 9 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA MH015 UT WOS:A1993MH01500011 ER PT J AU MYERS, CW DALY, JW AF MYERS, CW DALY, JW TI TROPICAL POISON FROGS SO SCIENCE LA English DT Letter C1 NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. RP MYERS, CW (reprint author), AMER MUSEUM NAT HIST,DEPT HERPETOL & ICHTHYOL,NEW YORK,NY 10024, USA. NR 6 TC 8 Z9 8 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 19 PY 1993 VL 262 IS 5137 BP 1193 EP 1193 DI 10.1126/science.8235639 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MH324 UT WOS:A1993MH32400002 PM 8235639 ER PT J AU MAHY, BWJ ALMOND, JW BERNS, KI CHANOCK, RM LVOV, DK PETTERSSON, RF SCHATZMAYR, HG FENNER, F AF MAHY, BWJ ALMOND, JW BERNS, KI CHANOCK, RM LVOV, DK PETTERSSON, RF SCHATZMAYR, HG FENNER, F TI THE REMAINING STOCKS OF SMALLPOX VIRUS SHOULD BE DESTROYED SO SCIENCE LA English DT Article ID DNA C1 DI IVANOVSKII INST VIROL,MOSCOW,RUSSIA. LUDWIG INST CANC RES,STOCKHOLM,SWEDEN. OSWALDO CRUZ FDN,DEPT VIROL,RIO JANEIRO,BRAZIL. UNIV READING,SCH ANIM & MICROBIAL SCI,READING RG6 2AH,BERKS,ENGLAND. CORNELL UNIV,MED CTR,COLL MED,DEPT MICROBIOL,NEW YORK,NY 10021. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. KAROLINSKA INST,S-10401 STOCKHOLM 60,SWEDEN. AUSTRALIAN NATL UNIV,JOHN CURTIN SCH MED RES,CANBERRA,ACT 2601,AUSTRALIA. RP MAHY, BWJ (reprint author), CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,ATLANTA,GA 30333, USA. NR 16 TC 30 Z9 30 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 19 PY 1993 VL 262 IS 5137 BP 1223 EP 1224 DI 10.1126/science.8235651 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MH324 UT WOS:A1993MH32400026 PM 8235651 ER PT J AU JOKLIK, WK MOSS, B FIELDS, BN BISHOP, DHL SANDAKHCHIEV, LS AF JOKLIK, WK MOSS, B FIELDS, BN BISHOP, DHL SANDAKHCHIEV, LS TI WHY THE SMALLPOX VIRUS STOCKS SHOULD NOT BE DESTROYED SO SCIENCE LA English DT Editorial Material ID VACCINIA VIRUS; MYXOMA VIRUS; COWPOX VIRUS; PROTEIN; RECEPTOR; ENCODES; PATHOGENESIS; INHIBITION C1 NERC,INST VIROL & ENVIRONM MICROBIOL,OXFORD OX1 3SR,ENGLAND. NPO VECTOR,INST MOLEC BIOL,KOLTSOV 632159,RUSSIA. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. RP JOKLIK, WK (reprint author), DUKE UNIV,DURHAM,NC 27710, USA. RI Sandakhchiev, Lev/B-7035-2012 NR 22 TC 24 Z9 24 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 19 PY 1993 VL 262 IS 5137 BP 1225 EP 1226 DI 10.1126/science.8235652 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MH324 UT WOS:A1993MH32400027 PM 8235652 ER PT J AU PATEL, A AF PATEL, A TI CHARACTERIZATION OF [I-125] RTI-55 BINDING TO DOG CAUDATE DOPAMINE TRANSPORTER SO NEUROREPORT LA English DT Article DE DOPAMINE; COCAINE; TRANSPORTER; UPTAKE; ASSAY; SOLUBILIZATION ID ASSAY AB WE have characterized binding of [I-125]RTI-55 ((-)-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane) to the dog caudate membrane and detergent solubilized dopamine transporter sites. The solubilized transporter was assayed by filtration over polyethylenimine treated Whatman GF/B filters. [I-125]RTI-55 specifically binds to transporter sites in membranes and solubilized protein with Kd of 0.27 and 0.34 nM, respectively. The binding of [I-125]RTI-55 to the membrane and solubilized transporter was inhibited by dopamine, norepinephrine and serotonin uptake inhibitors with rank order and potencies consistent with that of the dopamine transporter. Thus, similar pharmacological properties between membranes and solubilized dopamine transporters were retained upon solubilization. Rapid assay of solubilized protein will aid in monitoring transporter protein purification. RP PATEL, A (reprint author), NIDA,ADDICT RES CTR,MOLEC PHARMACOL LAB,NEUROSCI BRANCH,BALTIMORE,MD 21224, USA. NR 13 TC 2 Z9 2 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD NOV 18 PY 1993 VL 5 IS 2 BP 157 EP 160 DI 10.1097/00001756-199311180-00016 PG 4 WC Neurosciences SC Neurosciences & Neurology GA MH771 UT WOS:A1993MH77100016 PM 8111003 ER PT J AU DINSE, HR RECANZONE, GH MERZENICH, MM AF DINSE, HR RECANZONE, GH MERZENICH, MM TI ALTERATIONS IN CORRELATED ACTIVITY PARALLEL ICMS-INDUCED REPRESENTATIONAL PLASTICITY SO NEUROREPORT LA English DT Article DE SOMATOSENSORY CORTEX; POSTONTOGENETIC PLASTICITY; INTRACORTICAL MICROSTIMULATION; CROSS CORRELATION; CORTICAL NETWORK; CORRELATED ACTIVITY; NEURON ASSEMBLY; RECEPTIVE FIELDS; SYNCHRONIZATION; SIMULTANEOUS RECORDINGS ID VISUAL-CORTEX; MICROSTIMULATION; RESPONSES; CAT AB WE studied neural interactions by cross correlation analysis during representational plasticity induced by intracortical microstimulation (ICMS). Neuron pairs were simultaneously recorded in area 3b in adult New World monkeys, and in cortical field SI in adult rats. In normal animals, the degree of correlated spontaneous activity corresponded to the extent of receptive field overlap. After several hours of ICMS, the spatial extents of cortex over which correlated activity could be recorded was enlarged several-fold. Mapping experiments revealed that increased correlated activity was only recorded within that cortical sector that was representationally reorganized, indicating a close relationship between cortical reorganization and cooperative processes. Results support the hypothesis that discharge coincidence is crucial for the formation of functionally coupled neural groups, and implicate dynamically maintained groups in the genesis of postontogenetic plasticity. C1 UNIV CALIF SAN FRANCISCO,KECK CTR INTEGRAT NEUROSCI,SAN FRANCISCO,CA 94143. NIH,SENSORIMOTOR RES LAB,BETHESDA,MD 20892. RP DINSE, HR (reprint author), RUHR UNIV BOCHUM,LEHRSTUHL THEORET BIOL,INST NEUROINFORMAT,ND 04 BOX 102148,D-44780 BOCHUM,GERMANY. FU NINDS NIH HHS [NS-10414] NR 24 TC 51 Z9 52 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD NOV 18 PY 1993 VL 5 IS 2 BP 173 EP 176 DI 10.1097/00001756-199311180-00020 PG 4 WC Neurosciences SC Neurosciences & Neurology GA MH771 UT WOS:A1993MH77100020 PM 8111006 ER PT J AU GROOTHUIS, JR SIMOES, EAF LEVIN, MJ HALL, CB LONG, CE RODRIGUEZ, WJ ARROBIO, J MEISSNER, HC FULTON, DR WELLIVER, RC TRISTRAM, DA SIBER, GR PRINCE, GA VANRADEN, M HEMMING, VG AF GROOTHUIS, JR SIMOES, EAF LEVIN, MJ HALL, CB LONG, CE RODRIGUEZ, WJ ARROBIO, J MEISSNER, HC FULTON, DR WELLIVER, RC TRISTRAM, DA SIBER, GR PRINCE, GA VANRADEN, M HEMMING, VG TI PROPHYLACTIC ADMINISTRATION OF RESPIRATORY SYNCYTIAL VIRUS IMMUNE GLOBULIN TO HIGH-RISK INFANTS AND YOUNG-CHILDREN SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID INTRAVENOUS GAMMA-GLOBULIN; COTTON RATS; MATERNAL ANTIBODY; VIRAL-INFECTION; PULMONARY PATHOLOGY; EPIDEMIOLOGY; WASHINGTON; DISEASE; HOSPITALIZATION; IMMUNOTHERAPY AB Background. Infants with cardiac disease or prematurity are at risk for severe illness caused by respiratory syncytial virus. Immune globulin with a high titer of antibodies against respiratory syncytial virus may offer infants and young children at risk protection from this serious, common respiratory illness. Methods. We studied 249 infants and young children (mean age, eight months) who had bronchopulmonary dysplasia due to prematurity (n = 102), congenital heart disease (n = 87), or prematurity alone (n = 60). Respiratory syncytial virus immune globulin was given monthly to some of these children in either a high dose (750 mg per kilogram of body weight; n = 81) or a low dose (150 mg per kilogram; n = 79); 89 controls received no immune globulin. Group assignments were random. Assessments of respiratory illness and management were conducted without knowledge of the children's group assignments. Results. There were 64 episodes of respiratory syncytial virus infection: 19 in the high-dose group, 16 in the low-dose group, and 29 in the control group. In the high-dose group there were fewer lower respiratory tract infections (7, vs. 20 in the control group; P = 0.01), fewer hospitalizations (6, vs. 18 in the control group; P = 0.02), fewer hospital days (43, vs. 128 in the control group; P = 0.02), fewer days in the intensive care unit (P = 0.05), and less use of ribavirin (P = 0.05). In the low-dose group there was a significant reduction only in the number of days in the intensive care unit (P = 0.03). Adverse events during the 580 infusions were generally mild and included fluid overload (in five children), oxygen desaturation (eight), and fever (six). Six children died: three in the high-dose group, three in the low-dose group, and none in the control group (P = 0.15), but no death was attributed to the use of immune globulin or to illness caused by respiratory syncytial virus. Conclusions. Administration of high doses of respiratory syncytial virus immune globulin is a safe and effective means of preventing lower respiratory tract infection in infants and young children at high risk for this disease. C1 UNIV COLORADO,SCH MED,DEPT PEDIAT,DIV NEONATOL,DENVER,CO 80202. UNIV COLORADO,SCH MED,DEPT PEDIAT,DIV INFECT DIS,DENVER,CO 80202. UNIV COLORADO,SCH MED,DEPT PEDIAT,DIV CARDIOL,DENVER,CO 80202. STRONG MEM HOSP,DEPT PEDIAT,ROCHESTER,NY 14642. UNIV ROCHESTER,SCH MED,ROCHESTER,NY 14627. CHILDRENS HOSP,NATL MED CTR,WASHINGTON,DC 20010. TUFTS UNIV,FLOATING HOSP INFANTS & CHILDREN,DIV CARDIOL,BOSTON,MA 02111. TUFTS UNIV,FLOATING HOSP INFANTS & CHILDREN,DIV INFECT DIS,BOSTON,MA 02111. SUNY BUFFALO,CHILDRENS HOSP,MED CTR,DIV INFECT DIS,BUFFALO,NY 14260. MASSACHUSETTS PUBL HLTH BIOL LABS,BOSTON,MA. VIRION SYST,ROCKVILLE,MD. NIAID,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,F EDWARD HEBERT SCH MED,DEPT PEDIAT,BETHESDA,MD 20814. RP GROOTHUIS, JR (reprint author), CHILDRENS HOSP,1056 E 19TH AVE,B070,DENVER,CO 80218, USA. FU NCRR NIH HHS [M01-RR-00044, RR-69]; PHS HHS [N01-A1-82520] NR 45 TC 480 Z9 490 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 NOV 18 PY 1993 VL 329 IS 21 BP 1524 EP 1530 DI 10.1056/NEJM199311183292102 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA MG188 UT WOS:A1993MG18800002 PM 8413475 ER PT J AU HENNINGFIELD, JE AF HENNINGFIELD, JE TI MORE ON THE NICOTINE CONTENT OF VEGETABLES SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP HENNINGFIELD, JE (reprint author), NIDA,BALTIMORE,MD 21224, USA. NR 4 TC 9 Z9 10 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 NOV 18 PY 1993 VL 329 IS 21 BP 1581 EP 1581 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA MG188 UT WOS:A1993MG18800027 PM 8413489 ER PT J AU MULLER, CE DALY, JW AF MULLER, CE DALY, JW TI STIMULATION OF CALCIUM-RELEASE BY CAFFEINE ANALOGS IN PHEOCHROMOCYTOMA CELLS SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE XANTHINES; CALCIUM RELEASE; CAFFEINE ID ADRENAL CHROMAFFIN CELLS; INOSITOL 1,4,5-TRISPHOSPHATE; SYMPATHETIC NEURONS; ADENOSINE RECEPTORS; XENOPUS OOCYTES; CA2+ RELEASE; RYANODINE; CA-2+; POOL; OSCILLATIONS AB Caffeine (EC50 approximately 20 mM) causes a maximal 400% increase in intracellular calcium ion concentration ([Ca2+]i) in pheochromocytoma PC12 cells. A range of caffeine analogs in which methyl groups at the 1, 3, and 7 positions were replaced with relatively nonpolar (ethyl, allyl, propyl, propargyl) or polar (CH2COOH, CH2CH2OH, CH2CN, CH2OCH3) substituents were tested at a 10 mM concentration. Many analog were as efficacious or only somewhat less efficacious than 10 mM caffeine. Certain analogs with polar substituents had no effect. Disubstituted xanthines were less efficacious (theophylline, paraxanthine) than caffeine or were ineffective (theobromine). I-Propyl-3,7-dimethylxanthine (EC50 4 mM) and 1-propargyl-3,7-dimethylxanthine (EC50 5 mM) were several-fold more potent than caffeine in causing elevation of [Ca2+]i and the latter was at least as efficacious. C1 NIH,BLDG 8,RM 1A17,BETHESDA,MD 20892. RI Muller, Christa/C-7748-2014 OI Muller, Christa/0000-0002-0013-6624 NR 22 TC 20 Z9 20 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD NOV 17 PY 1993 VL 46 IS 10 BP 1825 EP 1829 DI 10.1016/0006-2952(93)90589-O PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MJ447 UT WOS:A1993MJ44700020 PM 8250969 ER PT J AU WORLAND, PJ KAUR, G STETLERSTEVENSON, M SEBERS, S SARTOR, O SAUSVILLE, EA AF WORLAND, PJ KAUR, G STETLERSTEVENSON, M SEBERS, S SARTOR, O SAUSVILLE, EA TI ALTERATION OF THE PHOSPHORYLATION STATE OF P34(CDC2) KINASE BY THE FLAVONE L86-8275 IN BREAST-CARCINOMA CELLS - CORRELATION WITH DECREASED H1 KINASE-ACTIVITY SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID P34CDC2 CYCLIN-B; TYROSINE PHOSPHORYLATION; CDC25 PROTEIN; M-PHASE; ACTIVATION; DEPHOSPHORYLATION; PHOSPHATASE; INHIBITION; ARREST; IDENTIFICATION AB The flavone L86-8275 [(-)cis-5,7-dihydroxy-2-(2-chlorophenyl)-8-[4-(3-hydroxy-1-methyl)-piperidinyl]-4H-1-benzopyran-4-one] delayed the progression of aphidicolin-synchronized MDA-468 breast carcinoma cells through S phase and prevented progression through G2. L86-8275 prevented the G2-related increase in histone HI kinase activity mediated by cyclin-dependent kinase-1 (p34cdc2 kinase). L86-8275 inhibited [P-32]orthophosphate labeling of p34cdc2 threonine and tyrosine residues and decreased the phosphotyrosine content of p34cdc2. Diminution of p34cdc2 phosphotyrosine appeared selective, as a general depletion of cellular phosphotyrosine was not observed. The mass of p34cdc2 in L86-8275-exposed cells was not decreased during the period over which these effects occurred. [S-35]Methionine labeling of p34cdc2 or other cellular proteins was not inhibited at concentrations that were effective for complete cellular growth inhibition. We hypothesize that L86-8275 interferes with the normal cell cycle-dependent phosphorylation of p34cdc2, resulting in decreased kinase activity and cell cycle arrest. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. RP WORLAND, PJ (reprint author), NCI,BIOL CHEM LAB,BETHESDA,MD 20892, USA. NR 27 TC 125 Z9 125 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD NOV 17 PY 1993 VL 46 IS 10 BP 1831 EP 1840 DI 10.1016/0006-2952(93)90590-S PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA MJ447 UT WOS:A1993MJ44700021 PM 8250970 ER PT J AU YANOVSKI, JA AF YANOVSKI, JA TI LOPERAMIDE TO DIAGNOSE CUSHINGS-SYNDROME - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP YANOVSKI, JA (reprint author), NIH,BETHESDA,MD 20892, USA. OI Yanovski, Jack/0000-0001-8542-1637 NR 2 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 NOV 17 PY 1993 VL 270 IS 19 BP 2302 EP 2302 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA MF993 UT WOS:A1993MF99300020 ER EF