FN Thomson Reuters Web of Science™ VR 1.0 PT J AU SCHWARTZENTRUBER, DJ STETLERSTEVENSON, M ROSENBERG, SA TOPALIAN, SL AF SCHWARTZENTRUBER, DJ STETLERSTEVENSON, M ROSENBERG, SA TOPALIAN, SL TI TUMOR-INFILTRATING LYMPHOCYTES DERIVED FROM SELECT B-CELL LYMPHOMAS SECRETE GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR AND TUMOR-NECROSIS-FACTOR-ALPHA IN RESPONSE TO AUTOLOGOUS TUMOR-STIMULATION SO BLOOD LA English DT Article ID NON-HODGKINS-LYMPHOMAS; ACTIVATED KILLER-CELLS; T-CELLS; INTERLEUKIN-2; NODES; DISEASE; CANCER; IMMUNOGLOBULIN; IMMUNOTHERAPY; REACTIVITY C1 NCI,DEPT PATHOL,BETHESDA,MD 20892. RP SCHWARTZENTRUBER, DJ (reprint author), NCI,SURG BRANCH,9000 ROCKVILLE PIKE,BLDG 10,RM 2B04,BETHESDA,MD 20892, USA. NR 27 TC 31 Z9 31 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 AUG 15 PY 1993 VL 82 IS 4 BP 1204 EP 1211 PG 8 WC Hematology SC Hematology GA LT742 UT WOS:A1993LT74200021 PM 8353284 ER PT J AU WEXLER, LH DELANEY, TF SARIS, S HOROWITZ, ME AF WEXLER, LH DELANEY, TF SARIS, S HOROWITZ, ME TI LONG-TERM SURVIVAL AFTER CENTRAL-NERVOUS-SYSTEM RELAPSE IN A PATIENT WITH OSTEOSARCOMA SO CANCER LA English DT Article DE OSTEOSARCOMA; BRAIN METASTASES; RADIATION THERAPY; ADJUVANT CHEMOTHERAPY ID METASTATIC OSTEOGENIC-SARCOMA; BRAIN METASTASIS; ADJUVANT CHEMOTHERAPY; PULMONARY METASTASES; SURGICAL RESECTION; SURGERY; IFOSFAMIDE; PATTERNS; CHILDREN; TUMORS AB Background. Since the advent of multiagent adjuvant chemotherapy, survival among patients with localized osteosarcoma has improved to 60% or more. Pulmonary relapse, the most common cause of treatment failure, is associated with less than 25% long-term survival; central nervous system (CNS) metastasis, when it occurs, often presents as a catastrophic clinical event in preterminal patients. Methods. The authors report a patient with osteosarcoma who had an isolated pulmonary relapse and a subsequent isolated CNS relapse. Complete surgical resection was accomplished on both occasions and followed in the initial instance by adjuvant chemotherapy and in the latter instance by adjuvant whole-brain irradiation. Results. An isolated CNS metastasis was resected and adjuvant whole brain irradiation was administered; the patient is alive and relapse free more than 5 years later. Conclusions. Patients with osteosarcoma in whom isolated, resectable metastases develop can derive benefit from gross total resection followed by adjuvant chemotherapy or radiation therapy for microscopic residual disease. C1 NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. RP WEXLER, LH (reprint author), NCI,PEDIAT BRANCH,9000 ROCKVILLE PIKE,BLDG 10,BETHESDA,MD 20892, USA. NR 39 TC 14 Z9 16 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 AUG 15 PY 1993 VL 72 IS 4 BP 1203 EP 1208 DI 10.1002/1097-0142(19930815)72:4<1203::AID-CNCR2820720412>3.0.CO;2-P PG 6 WC Oncology SC Oncology GA LR313 UT WOS:A1993LR31300011 PM 8339211 ER PT J AU SMART, CR HARTMANN, WH BEAHRS, OH GARFINKEL, L AF SMART, CR HARTMANN, WH BEAHRS, OH GARFINKEL, L TI INSIGHTS INTO BREAST-CANCER SCREENING OF YOUNGER WOMEN - EVIDENCE FROM THE 14-YEAR FOLLOW-UP OF THE BREAST-CANCER DETECTION DEMONSTRATION PROJECT SO CANCER LA English DT Article; Proceedings Paper CT WORKSHOP ON BREAST CANCER DETECTION IN YOUNGER WOMEN : A CURRENT ASSESSMENT CY FEB 01-02, 1993 CL NEW YORK, NY SP AMER CANC SOC ID GUIDELINES; MORTALITY; AGE C1 NCI,EARLY DETECT BRANCH,BETHESDA,MD 20892. MAYO CLIN & MAYO GRAD SCH MED,ROCHESTER,MN 55901. AMER CANC SOC,NEW YORK,NY 10017. AMER BOARD PATHOL,TAMPA,FL. NR 27 TC 46 Z9 47 U1 3 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD AUG 15 PY 1993 VL 72 IS 4 SU S BP 1449 EP 1456 DI 10.1002/1097-0142(19930815)72:4+<1449::AID-CNCR2820721406>3.0.CO;2-C PG 8 WC Oncology SC Oncology GA LR752 UT WOS:A1993LR75200005 PM 8339237 ER PT J AU METTLIN, CJ SMART, CR AF METTLIN, CJ SMART, CR TI THE CANADIAN-NATIONAL-BREAST-SCREENING-STUDY - AN APPRAISAL AND IMPLICATIONS FOR EARLY DETECTION POLICY SO CANCER LA English DT Article; Proceedings Paper CT WORKSHOP ON BREAST CANCER DETECTION IN YOUNGER WOMEN : A CURRENT ASSESSMENT CY FEB 01-02, 1993 CL NEW YORK, NY SP AMER CANC SOC ID DETECTION DEMONSTRATION PROJECT; CANCER-SOCIETY GUIDELINES; MORTALITY AB The recent reports from the Canadian National Breast Screening Study (CNBSS) address the effectiveness of breast cancer screening for women in the 40-49 age group and the benefit of adding mammography to standard clinical breast examination in women aged 50-59. Overall, the CNBSS results do not show reductions in breast cancer mortality after seven years of follow-up in either age group. The CNBSS is an important study that includes a large number of women, rigorous procedures, and thorough follow-up, but there are several caveats to interpreting these results. The study results reported to date are based on small numbers of end point events. There are questions about the effectiveness of the randomization procedures in creating cohorts that initially were at equal risk of breast cancer-related death. It also has been observed that the quality level of mammographic screens obtained at the beginning of the study were not as high as those obtained later. Future reports from the CNBSS are planned and may provide additional data helpful in interpreting the results. C1 NCI,EARLY DETECT BRANCH,BETHESDA,MD 20892. RP METTLIN, CJ (reprint author), ROSWELL PK CANC INST,666 ELM ST,BUFFALO,NY 14263, USA. NR 17 TC 25 Z9 25 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD AUG 15 PY 1993 VL 72 IS 4 SU S BP 1461 EP 1465 DI 10.1002/1097-0142(19930815)72:4+<1461::AID-CNCR2820721408>3.0.CO;2-S PG 5 WC Oncology SC Oncology GA LR752 UT WOS:A1993LR75200007 PM 8339239 ER PT J AU REED, E PARKER, RJ GILL, I BICHER, A DABHOLKAR, M VIONNET, JA BOSTICKBRUTON, F TARONE, R MUGGIA, FM AF REED, E PARKER, RJ GILL, I BICHER, A DABHOLKAR, M VIONNET, JA BOSTICKBRUTON, F TARONE, R MUGGIA, FM TI PLATINUM-DNA ADDUCT IN LEUKOCYTE DNA OF A COHORT OF 49 PATIENTS WITH 24 DIFFERENT TYPES OF MALIGNANCIES SO CANCER RESEARCH LA English DT Article ID OVARIAN-CANCER PATIENTS; INTERSTRAND CROSS-LINKS; HIGH-DOSE CISPLATIN; HUMAN-PLACENTA; LUNG-CANCER; CELL-LINES; REPAIR; CHEMOTHERAPY; QUANTITATION; CARCINOMA AB Using atomic absorbance spectrometry with Zeeman background correction, we measured platinum-DNA adduct levels in leukocyte DNA of 49 patients receiving therapy consisting of only carboplatin and cisplatin. Twenty-four histological types of malignancy were included in the cohort. Peripheral blood leukocytes were collected at defined times during the first two cycles of treatment. The relationship between adduct level and disease response was highly statistically significant during cycle 1 of therapy (two-sided P = 0.007 at day 2), but statistical significance was lost during cycle 2. On all days studied, median and mean adduct levels were consistently higher in responders as compared to nonresponders (summary two-sided P = 0.0004). These data suggest that the processes which protect cellular DNA may be common to malignant and nonmalignant rapidly dividing tissues of the same individual, regardless of the type of tumor that individual may harbor. C1 UNIV SO CALIF,LAC MED CTR,KENNETH NORRIS JR CANC CTR,LOS ANGELES,CA 90033. NCI,DIV CANC ETIOL,BETHESDA,MD 20892. RP REED, E (reprint author), NCI,MED BRANCH,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 45 TC 64 Z9 65 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 1993 VL 53 IS 16 BP 3694 EP 3699 PG 6 WC Oncology SC Oncology GA LR765 UT WOS:A1993LR76500010 PM 8339278 ER PT J AU MURASZKO, K SUNG, C WALBRIDGE, S GREENFIELD, L DEDRICK, RL OLDFIELD, EH YOULE, RJ AF MURASZKO, K SUNG, C WALBRIDGE, S GREENFIELD, L DEDRICK, RL OLDFIELD, EH YOULE, RJ TI PHARMACOKINETICS AND TOXICOLOGY OF IMMUNOTOXINS ADMINISTERED INTO THE SUBARACHNOID SPACE IN NONHUMAN-PRIMATES AND RODENTS SO CANCER RESEARCH LA English DT Article ID CEREBROSPINAL-FLUID SYSTEM; CENTRAL NERVOUS-SYSTEM; BREAST-CANCER; TRANSFERRIN RECEPTOR; MENINGEAL CARCINOMATOSIS; MONOCLONAL-ANTIBODY; LEPTOMENINGEAL NEOPLASIA; PURKINJE NEURONS; RHESUS-MONKEYS; CELL-LINES AB Immunotoxins have been suggested as possible therapeutic agents in patients with leptomeningeal carcinomatosis. The pharmacokinetics, stability, and toxicity of immunotoxins injected into the i.t. space were examined in rats and rhesus monkeys. Monoclonal antibodies specific for the human (454A12 and J1) and rat (OX26) transferrin receptors were coupled to recombinant ricin A chain. In monkeys, the maximally tolerated dose of the anti-human transferrin receptor immunotoxin (454A12-rRA) was a dose that yielded a nominal cerebrospinal fluid (CSF) concentration of approximately 1.2 x 10(-7)M. In rats, the 10% lethal dose (LD10) of the anti-human transferrin receptor immunotoxin was a dose yielding a nominal CSF concentration of 8.8 x 10(-7) M whereas the LD10 of the anti-rat transferrin receptor immunotoxin (OX26-rRA) was a dose yielding a nominal CSF concentration of 1.2 X 10(-7) M. Thus, the species-relevant antibody resulted in toxicity at a concentration one-seventh that of the immunotoxin with the irrelevant antibody. A comparison of the area under the concentration curve at the LD10 for rats with the area under the concentration curve at the maximally tolerated dose in monkeys and humans shows that the species-relevant immunotoxin was a better predictor of the toxic dose of the anti-transferrin receptor immunotoxin in humans than the irrelevant immunotoxin. The pharmacokinetics of the 454A12-rRA immunotoxin within the CSF of monkeys showed a biphasic clearance with an early-phase half-life of 1.4 h and a late phase half-life of 10.9 h. The clearance was 4.4 ml/h or approximately twice the estimated clearance due to bulk flow of CSF. Loss by degradation was ruled out because immunoblot analysis showed that the immunotoxin was stable for up to 24 h after administration. Possible losses in addition to sampling include diffusion into brain tissue and transcapillary permeation. The apparent volume of distribution was 10.1 ml or approximately three-fourths the total CSF volume of the monkey. Dose limiting toxicity corresponded with the selective elimination of Purkinje cells in both rats and monkeys and was manifested clinically as ataxia and lack of coordination. The onset of ataxia in monkeys occurred within 5 days and, in the more mild form, was reversible with time. There was evidence of only minimal inflammation within the CSF, and there were no signs of systemic toxicity. Immunotoxins injected into the subarachnoid space may have potential for treatment of leptomeningeal carcinomatosis. C1 NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. CETUS CORP,EMERYVILLE,CA 94608. RP MURASZKO, K (reprint author), NINCDS,SURG NEUROL BRANCH,BIOCHEM SECT,BETHESDA,MD 20892, USA. NR 53 TC 30 Z9 30 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 1993 VL 53 IS 16 BP 3752 EP 3757 PG 6 WC Oncology SC Oncology GA LR765 UT WOS:A1993LR76500021 PM 8339287 ER PT J AU YOKOTA, T MILENIC, DE WHITLOW, M WOOD, JF HUBERT, SL SCHLOM, J AF YOKOTA, T MILENIC, DE WHITLOW, M WOOD, JF HUBERT, SL SCHLOM, J TI MICROAUTORADIOGRAPHIC ANALYSIS OF THE NORMAL ORGAN DISTRIBUTION OF RADIOIODINATED SINGLE-CHAIN FV AND OTHER IMMUNOGLOBULIN FORMS SO CANCER RESEARCH LA English DT Article ID 2ND-GENERATION MONOCLONAL-ANTIBODIES; IMMUNE-COMPLEXES; HEPATIC-UPTAKE; TUMOR XENOGRAFTS; FAB FRAGMENTS; ATHYMIC MICE; B72.3; ANTIGEN; MELANOMA; TISSUE AB In Previous studies, we have compared the immunochemical properties, the in vivo pharmacokinetics, and the tumor penetrance of a radioiodinated single-chain Fv (sFv) in comparison with other immunoglobulin (Ig) forms (intact IgG, F(ab')2, and Fab') (Cancer Res., 51: 6363-6371, 1991). Biodistribution studies demonstrated a higher percent injected dose/g in the liver and spleen for the intact IgG and F(ab')2. Renal uptake was observed with the Fab' and F(ab')2, whereas the sFv demonstrated no specific localization in either of these organs. The I-125-labeled sFv also demonstrated a more even distribution throughout the tumor xenografts as compared to the other Ig forms (Cancer Res., 52: 3402-3408, 1992). Subsequent studies utilizing the sFv conjugated with a radiometal (Lu-177) demonstrated that the sFv was being metabolized by the kidney, and a significantly higher percent injected dose/g was obtained with a Lu-177 labeled sFv as compared to a I-125-labeled sFv (Cancer Res., 52: 6413-6417, 1992). These previous studies indicated the potential utility of radioiodinated sFv and other Ig fragments for use in radioimmunoguided surgery with a hand-held probe, diagnostic imaging, and possibly therapy. The present study compares the distribution in normal tissues of the 4 Ig forms of monoclonal antibody (MAb) CC49, which is directed against a pancarcinoma antigen (tumor-associated glycoprotein-72). I-125-labeled sFv, Fab', F(ab')2, and IgG of MAb CC49 were administered to athymic mice either bearing or not bearing the tumor-associated glycoprotein-72 positive human colon carcinoma xenograft (LS-174T). At various intervals following the i.v. injection of the Ig forms, the liver, spleen, kidneys, and lungs were removed for autoradiographic analyses. Dramatic differences were observed in the kidney; the IgG was found only in the renal vasculature, whereas the Fab', F(ab')2, and sFv showed a high density of grains in the cortical tubules. In the liver, the IgG and F(ab')2 were found in association with hepatocytes, Kupffer cells, and in the sinusoids; the Fab' and sFv were primarily associated with the Kupffer cells. In the spleen, the Ig forms localized to the marginal zones surrounding the lymphoid follicles. No specific accumulation of grains for any of the Ig forms was observed in the lung. In each of the tissues, the clearance rates were related to the size of the Ig form. The localization in the liver and spleen was determined to be antigen-mediated. No specific localization was observed when I-125-labeled BL-3, an isotype-matched control MAb, was injected into tumor-bearing mice, or, when the I-125-labeled CC49 IgG was administered to non-tumor-bearing mice. By defining the interactions of a MAb and its modified forms not only with tumor lesions but also with normal organs and tissues, more rational protocols for uses of a MAb and its various forms, including sFv's, can be designed for diagnostic and therapeutic applications. C1 NCI,TUMOR IMMUNOL & BIOL LAB,9000 ROCKVILLE PIKE,BLDG 10,ROOM 8B07,BETHESDA,MD 20892. ENZON INC,GAITHERSBURG,MD 20877. NR 45 TC 111 Z9 112 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 1993 VL 53 IS 16 BP 3776 EP 3783 PG 8 WC Oncology SC Oncology GA LR765 UT WOS:A1993LR76500025 PM 8339291 ER PT J AU BRUNATI, AM JAMES, P DONELLADEANA, A MATOSKOVA, B ROBBINS, KC PINNA, LA AF BRUNATI, AM JAMES, P DONELLADEANA, A MATOSKOVA, B ROBBINS, KC PINNA, LA TI ISOLATION AND IDENTIFICATION OF 2 PROTOONCOGENE PRODUCTS RELATED TO C-FGR AND FYN IN A TYROSINE-PROTEIN-KINASE FRACTION OF RAT SPLEEN SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article ID PEPTIDES; CSK AB TPK-III, a tyrosine-protein-kinase fraction previously isolated from rat spleen [Brunati, A. M. & Pinna, L. A. (1988) Eur J. Biochem. 172, 451-457] has been further purified and resolved by Mono-Q FPLC into two homogeneous compounds, Ql and Q2, with molecular mass approximately 52 kDa, exhibiting high specific activities for phosphate incorporation into the phosphoacceptor substrate poly(Glu80Tyr20) (1194 nmol.min-1.mg-1 and 579 nmol.min-1.mg-1, respectively). Both Q1 and Q2 appear to be scr-related enzymes since they are readily recognised by anti-SEEP serum raised against the highly conserved segment at positions 330-345 of p60c-scr. Q1, but not Q2, interacts with a specific antibody raised against the N-terminal segment of p55c-fgr. Microsequence analysis of tryptic fragments generated from Ql revealed five peptides which exactly overlap the expected segments of p55c-fgr. Two of these peptides were not entirely conserved in any of the other src-related tyrosine protein kinases. A sixth fragment is very similar, albeit not identical, to the C-terminus of p55c-fgr. Microsequence analysis of two tryptic fragments from the other TPK-III fraction, Q2, provided the sequences FQILNSSE and LTTQETGYIPSNY, which are identical to two segments of fyn not entirely conserved in any of the other src-related tyrosine protein kinases. These results provide evidence that the spleen tyrosine-protein-kinase fraction, conventionally designated TPK-III, is composed of products from two proto-oncogenes, one of which corresponds to fyn, while the other is either identical or very closely related to c-fgr. C1 UNIV PADUA, CNR, DIPARTIMENTO CHIM BIOL, VIA TRIESTE 75, I-35121 PADUA, ITALY. UNIV PADUA, CNR, CTR STUDIO FISIOL MITOCONDRIALE, I-35121 PADUA, ITALY. SWISS FED INST TECHNOL, CH-8093 ZURICH, SWITZERLAND. NIDR, CELLULAR DEV & ONCOL LAB, BETHESDA, MD 20892 USA. NR 11 TC 34 Z9 34 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD AUG 15 PY 1993 VL 216 IS 1 BP 323 EP 327 DI 10.1111/j.1432-1033.1993.tb18149.x PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LT620 UT WOS:A1993LT62000038 PM 8365414 ER PT J AU MIYASAKA, H CHOUDHURY, BK HOU, EW LI, SSL AF MIYASAKA, H CHOUDHURY, BK HOU, EW LI, SSL TI MOLECULAR-CLONING AND EXPRESSION OF MOUSE AND HUMAN CDNA-ENCODING AES AND ESG PROTEINS WITH STRONG SIMILARITY TO DROSOPHILA ENHANCER OF SPLIT GROUCHO PROTEIN SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article ID BETA-SUBUNIT; SACCHAROMYCES-CEREVISIAE; TYROSINE-PHOSPHATASE; LEUCINE ZIPPER; GENE-PRODUCT; SEQUENCE; HOMOLOGY; REPRESSION; CELLS; CDC4 AB Mouse and human cDNA encoding AES (amino-terminal enhancer of split) and ESG (enhancer of split groucho) proteins with strong similarity to Drosophila enhancer of split groucho protein were isolated and sequenced. Mouse AES-1 and AES-2 proteins, probably resulting from alternative splicing, contain 202 and 196 amino acids, respectively, while mouse ESG protein consists of 771 amino acids. The amino acid sequences of mouse and human AES proteins were found to exhibit approximately 50% identity to the amino-terminal region of Drosophila groucho, mouse ESG and human transducin-like enhancer of split (TLE) proteins. Mouse AES transcripts of 1.5 kb and 1.2 kb were abundantly expressed in muscle, heart and brain. Human AES transcripts of 1.6 kb and 1.4 kb were predominantly present in muscle, heart and placenta. Mouse ESG (homolog of human TLE 3) transcripts of 3.3 kb and 4.0 kb were found only in testis, while human TLE 1 transcripts of 4.5 kb was more abundant in muscle and placenta compared to heart, brain, lung, liver, kidney and pancreas. Human AES, TLE 1 and TLE 3 genes were mapped to chromosomes 19, 9 and 15, respectively, using human and Chinese hamster hybrid cell lines. C1 NIEHS,GENET LAB,MAIL DROP D3-05,POB 12233,RES TRIANGLE PK,NC 27709. NR 20 TC 62 Z9 65 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD AUG 15 PY 1993 VL 216 IS 1 BP 343 EP 352 DI 10.1111/j.1432-1033.1993.tb18151.x PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LT620 UT WOS:A1993LT62000040 PM 8365415 ER PT J AU RAMKUMAR, V STILES, GL BEAVEN, MA ALI, H AF RAMKUMAR, V STILES, GL BEAVEN, MA ALI, H TI THE A(3) ADENOSINE RECEPTOR IS THE UNIQUE ADENOSINE RECEPTOR WHICH FACILITATES RELEASE OF ALLERGIC MEDIATORS IN MAST-CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID MOLECULAR-CLONING; LIGAND-BINDING; RBL-2H3 CELLS; EXPRESSION; SUBTYPES AB Mast cells release the mediators of the immediate hypersensitivity reaction. Adenosine is known to modulate this process, but the receptor responsible for this is not the classical A1 or A2 adenosine receptors. This study was undertaken to determine whether the unique adenosine receptor (AR) previously postulated in a cultured mast cell line (RBL-2H3 cells) is the recently cloned A3AR. The receptors were quantitated by the agonist I-125-labeled APNEA (aminophenylethyladenosine), an A3AR agonist, which yielded B(max) and K(d) values of 826 fmol/mg protein and 34 nM, respectively. A variety of adenosine analogs competed for I-125-APNEA binding sites with the following potency series: (R)-phenylisopropyladenosine = 5'-N-ethylcarboxamide adenosine > (S)-phenylisopropyladenosine. I-125-APNEA binding was relatively insensitive to the xanthine amine congener (XAC, 1 muM), a selective antagonist for the A1AR. Functionally, activation of these A3AR stimulated the production of inositol 1,4,5-triphosphate, leading to an increase in the level of intracellular Ca2+. Furthermore, while activation of these receptors alone produced little secretory response in RBL-2H3 cells, it enhanced antigen-induced secretion by 2-2.5-fold. Northern blotting studies using poly(A+) RNA from RBL-2H3 cells detected two transcripts of 2.0 and 3.5 kilobases, which hybridized to an A3AR cDNA but not to the A1 or A2AR cDNA probes. These data indicate that the unique AR that potentiates the secretory response to antigen in RBL-2H3 cells is exclusively the A3AR. C1 DUKE UNIV,MED CTR,DEPT PHARMACOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT MED CARDIOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT MED RHEUMATOL & IMMUNOL,DURHAM,NC 27710. NHLBI,CHEM PHARMACOL LAB,BETHESDA,MD 20892. RP RAMKUMAR, V (reprint author), SO ILLINOIS UNIV,SCH MED,DEPT PHARMACOL,801 N RUTLEDGE ST,SPRINGFIELD,IL 62794, USA. NR 26 TC 374 Z9 378 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 AUG 15 PY 1993 VL 268 IS 23 BP 16887 EP 16890 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LQ988 UT WOS:A1993LQ98800005 PM 8349579 ER PT J AU COOK, RM BURKE, BJ BUCHHAGEN, DL MINNA, JD MILLER, YE AF COOK, RM BURKE, BJ BUCHHAGEN, DL MINNA, JD MILLER, YE TI HUMAN AMINOACYLASE-1 - CLONING, SEQUENCE, AND EXPRESSION ANALYSIS OF A CHROMOSOME-3P21 GENE INACTIVATED IN SMALL-CELL LUNG-CANCER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACYLPEPTIDE HYDROLASE; KIDNEY AMINOACYLASE; DNF15S2 LOCUS; PIG-KIDNEY; 3P21; HETEROZYGOSITY; PURIFICATION; SIMILARITY; DEFICIENCY; CARCINOMA AB Human aminoacylase-1 (N-acyl-L-amino-acid amidohydrolase, EC 3.5.1.14; ACY1) is a homodimeric zinc-binding enzyme that catalyzes the hydrolysis of N(alpha)-acylated amino acids. ACY1 has been assigned to chromosome 3p21.1, a region reduced to homozygosity in small cell lung cancer (SCLC), and has been reported to exhibit reduced or absent expression in SCLC cell lines and tumors. Two human cDNA libraries and one human genomic DNA library were screened with a previously isolated partial ACY1 cDNA to isolate a full-length transcript. Sequence analysis of clones from each of these libraries resulted in an ACY1 cDNA of 1438 base pairs with an open reading frame of 1224-base pairs coding for a putative protein of 408 amino acids with a predicted molecular mass of 45,882 Da. Sequence analysis revealed no homologies to previously reported cDNA or protein sequences and establishes ACY1 as the first member of a new family of zinc-binding enzymes to be so characterized. The subcellular location of ACY1 has been established as cytosolic by flow cytometry. Southern and northern analyses of ACY1 in SCLC cell lines failed to demonstrate any gross abnormalities of the ACY1 structural gene or instances of absent or aberrantly sized mRNA, respectively. C1 UNIV COLORADO,HLTH SCI CTR,DIV PULM SCI & CRIT CARE MED,DENVER,CO 80262. USN HOSP,NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20889. UNIV TEXAS,SW MED CTR,SIMMONS COMPREHENS CANC CTR,DALLAS,TX 75235. UNIFORMED SERV UNIV HLTH SCI,DEPT MED,BETHESDA,MD 20814. RP COOK, RM (reprint author), VET ADM MED CTR,111A,DENVER,CO 80220, USA. FU NCI NIH HHS [P50 CA58187]; NHLBI NIH HHS [HL-07085, R01 HL45745] NR 33 TC 41 Z9 42 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 AUG 15 PY 1993 VL 268 IS 23 BP 17010 EP 17017 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LQ988 UT WOS:A1993LQ98800022 PM 8394326 ER PT J AU TRAINER, VL MOREAU, E GUEDIN, D BADEN, DG CATTERALL, WA AF TRAINER, VL MOREAU, E GUEDIN, D BADEN, DG CATTERALL, WA TI NEUROTOXIN BINDING AND ALLOSTERIC MODULATION AT RECEPTOR SITE-2 AND SITE-5 ON PURIFIED AND RECONSTITUTED RAT-BRAIN SODIUM-CHANNELS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SCORPION TOXIN BINDING; PYRETHROID INSECTICIDES; BREVETOXINS; SYNAPTOSOMES; BATRACHOTOXININ; PURIFICATION; MEMBRANES; SUBUNIT AB Purified and reconstituted sodium channels have previously been shown to be functional in voltage-dependent ion conductance and in high affinity binding of tetrodotoxin and saxitoxin at neurotoxin receptor site 1 and alpha-scorpion toxins at receptor site 3, but high affinity binding of neurotoxins at receptor sites 2, 4, and 5 has not been demonstrated. The pyrethroid insecticide RU39568 enhances the specific binding of [H-3]batrachotoxinin A 20-alpha-benzoate (BTX-B) to neurotoxin receptor site 2 on purified and reconstituted sodium channels up to 500-fold, reducing the K(d) to 1.5 nm. Brevetoxins and alpha-scorpion toxins cause further allosteric enhancement of BTX-B binding. The pyrethroids deltamethrin and bifenthrin and the nonpyrethroid insecticide 2,2-bis(p-chlorophenyl)trichloroethane can partially substitute for RU39568 in enhancing BTX-B binding, but other pyrethroids are inactive. The brevetoxin PbTx-1 binds specifically to neurotoxin receptor site 5 on purified and reconstituted sodium channels with a K(d) value of approximately 30 nM. Brevetoxin binding is enhanced up to 2-fold by the combination of batrachotoxin and RU39568. The allosteric enhancement of BTX-B binding by RU39568 is voltage dependent, decreasing progressively with depolarization to 0 mV. In contrast, PbTx-1 binding is not voltage dependent and PbTx-1 reduces the voltage dependence of the effect of RU39568. The results demonstrate restoration of high affinity binding and allosteric interactions of ligands at neurotoxin receptor sites 2 and 5 on purified and reconstituted sodium channels and provide an experimental approach to covalent labeling and identification of the peptide components of those receptor sites. C1 ROUSSEL UCLAF,CTR RECH,F-93230 ROMAINVILLE,FRANCE. UNIV MIAMI,NIEHS,CTR MARINE & FRESHWATER BIOMED SCI,MIAMI,FL 33149. RP TRAINER, VL (reprint author), UNIV WASHINGTON,DEPT PHARMACOL,SJ-30,SEATTLE,WA 98195, USA. FU NIEHS NIH HHS [F32 ES 05586, P30 ES 05705] NR 24 TC 53 Z9 54 U1 1 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 AUG 15 PY 1993 VL 268 IS 23 BP 17114 EP 17119 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LQ988 UT WOS:A1993LQ98800037 PM 8394327 ER PT J AU CHANDLER, P PENNINGTON, M MACCECCHINI, ML NASHED, NT SKOLNICK, P AF CHANDLER, P PENNINGTON, M MACCECCHINI, ML NASHED, NT SKOLNICK, P TI POLYAMINE-LIKE ACTIONS OF PEPTIDES DERIVED FROM CONANTOKIN-G, AN N-METHYL-D-ASPARTATE (NMDA) ANTAGONIST SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECEPTOR IONOPHORE COMPLEX; GAMMA-CARBOXYGLUTAMATE; PROTEIN CONFORMATION; RECOGNITION SITE; MODULATORY SITE; CHANNEL COMPLEX; MK-801 BINDING; GLYCINE SITE; ION CHANNEL; L-GLUTAMATE AB Conantokins-T and -G are highly conserved polypeptides derived from Conus venoms. The N-methyl-D-aspartate (NMDA) antagonist properties of these compounds have been attributed to a potent noncompetitive inhibition of polyamine responses. Substitution of the highly conserved gamma-carboxyglutamate residues as well as modification of the N and C termini of conantokin-G abolished the inhibition of polyamine responses at the NMDA receptor complex. However, several of these modified polypeptides closely mimicked the neurochemical profile of polyamines at the NMDA receptor complex. One of these derivatives, Tyr0-conantokin-G, was found to be the most potent compound exhibiting polyamine-like actions at the NMDA receptor complex described to date, approximately 7-fold more potent than spermine. Circular dichroism studies demonstrate a significant alpha-helical content in conantokin-G (27% in aqueous medium). However, this alpha-helicity is not sufficient for the NMDA antagonist action of the parent peptide and is neither necessary nor sufficient for the polyamine-like behavior of several conantokin-G analogs. The modified conantokin-G derivatives described in this report should be useful probes for examining the role of both polyamines and the polyamine recognition site in the operation of the NMDA receptor complex. C1 NIDDK,NEUROSCI LAB,BLDG 8,RM 111,BETHESDA,MD 20892. NIDDK,BIOORGAN LAB,BETHESDA,MD 20892. BACHEM BIOSCI,PHILADELPHIA,PA 19104. NR 39 TC 45 Z9 46 U1 1 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 AUG 15 PY 1993 VL 268 IS 23 BP 17173 EP 17178 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LQ988 UT WOS:A1993LQ98800046 PM 8349604 ER PT J AU MORRISON, DK HEIDECKER, G RAPP, UR COPELAND, TD AF MORRISON, DK HEIDECKER, G RAPP, UR COPELAND, TD TI IDENTIFICATION OF THE MAJOR PHOSPHORYLATION SITES OF THE RAF-1 KINASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SERINE THREONINE KINASE; COMPLETE CODING SEQUENCE; PROTEIN-KINASE; MAP KINASE; SIGNAL TRANSDUCTION; TYROSINE PHOSPHORYLATION; REGULATORY PHOSPHORYLATION; TRANSFORMING ACTIVITY; 3T3 CELLS; V-RAF AB Treatment of cells with various growth factors and mitogens results in the rapid hyperphosphorylation and activation of the Raf-1 kinase. To determine if phosphorylation events affect Raf-1 activity, we have initiated experiments to identify the phosphorylation sites of Raf-1. In this report, we find that Ser43, Ser259, and Ser621 are the major sites of Raf-1 which are phosphorylated in mammalian cells and in Sf9 insect cells infected with a recombinant baculovirus encoding human Raf-1. Mutant Raf-1 proteins lacking kinase activity are also phosphorylated on these sites in vivo, indicating that these phosphorylation events are not a consequence of autophosphorylation. Furthermore, we find that Thr268 is the predominant Raf-1 residue phosphorylated in in vitro autokinase assays. In addition, we have examined the biochemical activity of baculovirus-expressed Raf-1 proteins containing mutations at these phosphorylation sites. In in vitro protein kinase assays Ser259 mutant proteins were 2-fold more active than wild-type Raf-1 and Ser621 mutant proteins were inactive as kinases. Analysis of the residues surrounding Ser259 and Ser621 indicates that RSXSAP may be a consensus sequence for the kinase responsible for phosphorylation of Raf-1 at these sites. Interestingly, these RSXSXP sequences are completely conserved throughout evolution in all Raf family members. C1 NCI, FREDERICK CANC RES & DEV CTR, VIRAL CARCINOGENESIS LAB, VIRAL PATHOL SECT, FREDERICK, MD 21702 USA. RP NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. FU NCI NIH HHS [N01-CO-74101] NR 59 TC 269 Z9 272 U1 0 U2 2 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 AUG 15 PY 1993 VL 268 IS 23 BP 17309 EP 17316 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LQ988 UT WOS:A1993LQ98800064 PM 8349614 ER PT J AU UHLINHANSEN, L YANAGISHITA, M AF UHLINHANSEN, L YANAGISHITA, M TI DIFFERENTIAL EFFECT OF BREFELDIN-A ON THE BIOSYNTHESIS OF HEPARAN-SULFATE AND CHONDROITIN DERMATAN SULFATE PROTEOGLYCANS IN RAT OVARIAN GRANULOSA-CELLS IN CULTURE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN LINKAGE REGION; ENDOPLASMIC-RETICULUM; SHARK CARTILAGE; GOLGI PROTEINS; TRANSPORT; ER AB The subcellular localization of the enzymes involved in the glycosylation of proteoglycans was studied in rat ovarian granulosa cells by interfering with the normal traffic in the Golgi apparatus using brefeldin A. Cell cultures were metabolically labeled with [S-35] sulfate and [H-3]glucosamine, and the radiolabeled macromolecules were analyzed by ion-exchange and gel chromatography in combination with chondroitinase or heparitinase treatment. In the absence of brefeldin A, the cells synthesized both dermatan sulfate proteoglycans (DSPGs) and heparan sulfate proteoglycans (HSPGs) which were isolated from the culture medium, the plasma membrane, and intracellular compartments. However, in the presence of brefeldin A, the synthesized proteoglycans were almost exclusively HSPGs and were found only in the intracellular compartment. Analyses of HSPGs synthesized in the presence of brefeldin A indicated that: (i) the HS chains are synthesized on the same core protein as for the normal HSPGs; (ii) the chains are two to three times the normal molecular size; and (iii) a significant proportion of the HS chains are normally sulfated. Brefeldin A induces a disassembly of the proximal part of the Golgi complex, resulting in a redistribution of cis-, medial-, and trans-Golgi resident enzymes back to the endoplasmic reticulum (ER), and blocks the transport of proteins to the trans-Golgi network. Our results indicate that the complete set of enzymes involved in the biosynthesis of HS chains are localized in the ER/proximal part of the Golgi complex, whereas the enzymes involved in the elongation/sulfation of DS chains are exclusively located in the trans-Golgi network. Furthermore, our results indicate that the enzymes involved in the biosynthesis of HS chains are specific to HS core proteins, since no DS core proteins were substituted with HS chains in the presence of brefeldin A. C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. NR 25 TC 49 Z9 49 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 AUG 15 PY 1993 VL 268 IS 23 BP 17370 EP 17376 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LQ988 UT WOS:A1993LQ98800072 PM 8349620 ER PT J AU LEI, KJ WANG, C CHAMBERLIN, ME LIU, JL PAN, CJ CHOU, JY AF LEI, KJ WANG, C CHAMBERLIN, ME LIU, JL PAN, CJ CHOU, JY TI CHARACTERIZATION OF 2 ALLELIC VARIANTS OF A HUMAN PREGNANCY-SPECIFIC GLYCOPROTEIN GENE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN CARCINOEMBRYONIC ANTIGEN; DNA-BINDING; MOLECULAR-CLONING; BETA-1-GLYCOPROTEIN FAMILY; CDNA SEQUENCE; FETAL LIVER; CEA FAMILY; CACCC-BOX; PROTEINS; SP1 AB The pregnancy-specific glycoproteins (PSGs) of the human placenta are a group of proteins that together with the carcinoembryonic antigens comprise a subfamily within the immunoglobulin superfamily. To study the control of PSG expression, we isolated and characterized PSG genes and identified cis-acting DNA elements in the 5'-flanking gene regions essential for PSG expression. Two overlapping PSG cosmid clones, which contain two allelic variants of a PSG gene (PSG12 and PSG12psi), were isolated from an unamplified library made from a single individual. Cosmid 1 contains exons 1 (5'/L) and 2 (L/N) of the PSG12 gene located downstream of a previously identified PSG1-I gene. Cosmid 6 contains a portion of the PSG1-I gene lacking exons 1 and 2 upstream of a complete PSG12psi transcription unit. Sequence comparison indicates that exons 5'/L and L/N in PSG12 and PSG12psi are 99% identical, except that the L/N exon in the PSG12psi gene contains a stop codon. Both PSG12 and PSG12psi transcripts were detected in the human placenta, indicating that both genes are actively transcribed. However, the PSG12psi gene may represent an allelic pseudogene variant of the PSG12 gene, because all identified PSGs contain a functional N-domain. Primer extension analysis showed that the PSG12 gene starts at a cluster of sites located at -106 to -104 base pairs with respect to the translation start site. In transient transfection assays using a chloramphenicol acetyltransferase reporter gene, we demonstrated that the -835 to -34 DNA region upstream of the translation start site of PSG12 or PSG12psi contained both positive and negative elements that control PSG expression. Deletion analysis showed that nucleotides -172 to -34 in the PSG12 gene could function as a promoter. Gel retardation analysis showed that protein factors in human placental cell extract formed four complexes (I, II, IIa, and III) with the PSG12(-172/-34) DNA. Site-directed mutagenesis that prevents protein factor binding to the PSG12 promoter resulted in a marked reduction in transcription activation, locating the core enhancers at nucleotides-148 to -141 and -60 to -55. Mutagenesis studies also showed that the ACAGC repeats at nucleotides -84 to -68 in the PSG12 5'-flanking are essential for expression of the PSG12 gene in human placental cells. C1 NICHHD,HUMAN GENET BRANCH,BLDG 10,RM 95242,BETHESDA,MD 20892. NR 63 TC 14 Z9 14 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 AUG 15 PY 1993 VL 268 IS 23 BP 17528 EP 17538 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LQ988 UT WOS:A1993LQ98800093 PM 8349632 ER PT J AU KOKUBO, T TAKADA, R YAMASHITA, S GONG, DW ROEDER, RG HORIKOSHI, M NAKATANI, Y AF KOKUBO, T TAKADA, R YAMASHITA, S GONG, DW ROEDER, RG HORIKOSHI, M NAKATANI, Y TI IDENTIFICATION OF TFIID COMPONENTS REQUIRED FOR TRANSCRIPTIONAL ACTIVATION BY UPSTREAM STIMULATORY FACTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA POLYMERASE-II; TATA BOX-BINDING; PREINITIATION COMPLEX; PROMOTER INTERACTIONS; PROTEIN; DOMAIN; INITIATION; REGION; GENE; DNA AB A TATA box-binding initiation factor, TFIID, plays a central role in the transcriptional regulation by activators. Using anti-TFIIDtau (a TATA box-binding component of native TFIID) immunoaffinity chromatography, nine polypeptides (230, 110, 85, 62, 58, 42, 28, 22, and 21 kDa) were identified as native Drosophila TFIID components that are tightly associated with TFIIDtau. To verify the functional activity of the purified TFIID complex, template DNA and other transcription factors were reconstituted with purified TFIID bound to the antibody-Sepharose matrix. Immobilized TFIID mediated not only basal transcription but transcriptional activation by upstream stimulatory factor (USF). On the other hand, recombinant TFIIDtau immobilized on the same antibody-Sepharose matrix could not mediate activation by USF. These results suggest that one or more of these additional polypeptides are required as functional TFIID subunits for activator-dependent transcription in conjunction with TFIIDtau. As further evidence of the relevance of the Drosophila TFIID components identified in this analysis, including the previously unrecognized p230 (Dynlacht, B. D., Hoey, T., and Tjian, R. (1991) Cell 66, 563-576), protein blot analysis showed that TFIIDtau interacts specifically and exclusively with p230. This suggests that p230 is an integral subunit of TFIID and that it may play a major role in tethering other subunits to TFIIDtau. C1 NIMH,DIV BIOMETRY & EPIDEMIOL,BLDG PK 5,RM 415,ROCKVILLE,MD 20857. ROCKEFELLER UNIV,BIOCHEM & MOLEC BIOL LAB,NEW YORK,NY 10021. UNIV TOKYO,INST APPL MICROBIOL,BUNKYO KU,TOKYO 113,JAPAN. FU NCI NIH HHS [CA42567]; NIAID NIH HHS [AI27397]; NIGMS NIH HHS [GM45258] NR 28 TC 46 Z9 46 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 15 PY 1993 VL 268 IS 23 BP 17554 EP 17558 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LQ988 UT WOS:A1993LQ98800096 PM 8349634 ER PT J AU CHANG, AC WADSWORTH, S COLIGAN, JE AF CHANG, AC WADSWORTH, S COLIGAN, JE TI EXPRESSION OF MEROSIN IN THE THYMUS AND ITS INTERACTION WITH THYMOCYTES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXTRACELLULAR-MATRIX COMPONENTS; BASEMENT-MEMBRANE PROTEINS; NEURITE-PROMOTING FACTOR; T-CELL SUBSETS; REGULATED EXPRESSION; MONOCLONAL-ANTIBODY; ADHESION RECEPTORS; INTEGRIN RECEPTORS; LYMPHOID-TISSUES; A-CHAIN AB Merosin is a 700 kDa multichain protein that has several properties in common with laminin, one of the major extracellular matrix proteins present in basement membranes. Both contain B1 and B2 light chains, but merosin has a distinct M-chain compared with the laminin A-chain. Merosin is present in the basement membrane of placenta, striated muscle, and peripheral nerve. Using the RT-PCR assay, we demonstrate that merosin, but not laminin, is also expressed in the thymus. A partial cDNA sequence of the mouse merosin M-chain was 88% identical to the human M-chain, and the deduced amino acid sequences were 95% identical. 18-24% of adult mouse thymocytes bound to human merosin in vitro. Mg2+, but not Ca2+, was essential for binding. Binding was inhibited by antibodies recognizing VLA alpha6 or beta1, suggesting that the VLA-6 integrin is a merosin receptor. An anti-beta4 integrin subunit mAb failed to inhibit binding, suggesting that the alpha6beta4 integrin was not involved. Thymocytes were fractionated into immature and mature populations based on their expression of the heat stable antigen, recognized by the J11d mAb. Virtually all, thymocytes expressed VLA-6, but only immature thymocytes (J11d+) bound to merosin. PMA treatment did n-ot significantly increase the binding of J11d+ thymocytes nor did it induce binding in the mature J11d- population. In contrast, both splenic T cells and unseparated lymph node cells showed enhanced binding to merosin after PMA stimulation. The expression of merosin in the thymus and its selective interaction with immature thymocytes suggest that thymocyte-merosin interactions may play a role in T cell development. C1 NIAID,BIOL RESOURCES BRANCH,BLDG 4,ROOM 413,BETHESDA,MD 20892. NR 62 TC 40 Z9 41 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 1993 VL 151 IS 4 BP 1789 EP 1801 PG 13 WC Immunology SC Immunology GA LR904 UT WOS:A1993LR90400005 PM 8345183 ER PT J AU MARINE, JB SHIRAKATA, Y WADSWORTH, SA HOOLEY, JJ HANDY, DE COLIGAN, JE AF MARINE, JB SHIRAKATA, Y WADSWORTH, SA HOOLEY, JJ HANDY, DE COLIGAN, JE TI ROLE OF THE Q10 CLASS-I REGULATORY ELEMENT REGION-1 IN CONTROLLING TISSUE-SPECIFIC EXPRESSION IN-VIVO SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; PRE-MESSENGER RNA; NF-KAPPA-B; TRANSCRIPTION FACTORS; MOUSE; GENE; SEQUENCE; BINDING; ENHANCER; MOLECULE AB The MHC class I regulatory element (CRE) region 1 has been previously described as a positive cis-acting regulatory element essential for class I gene expression. We have generated transgenic mice (CBA x C57BL/6) with the MHC class I gene H-2D(d) driven by two different 400-bp promoter regions of Q10, a nonpolymorphic MHC class I gene expressed in the liver, kidney, and fetal yolk sac. One transgene contained the wild-type Q10 promoter (Q10WT/D(d)). The second construct (Q10M3/D(d)) had 2 bp substitutions introduced in region 1 of the CRE that reconstituted the CRE inverted repeat present in classical class I genes. Mice containing the wild-type Q10/D(d) gene expressed membrane-bound H-2D(d) molecules in a tissue-restricted expression pattern similar to that observed for endogenous Q10. In mice containing the mutant construct (Q10M3/D(d)), H-2D(d) was also expressed in the thymus, a tissue not normally associated with Q10 expression but, surprisingly, the D(d) was not expressed in other lymphoid tissues. Furthermore, thymic expression was greatest on double positive (CD4+ CD8+) thymocytes. Thymic D(d) expression was correlated with the presence of what appears to be a previously unidentified transcription factor in thymocytes that is capable of interacting with the CRE-inverted repeat. These results show that the mutations in region 1 altered the tissue-specific regulation of the Ql 0 promoter in vivo, although an intact inverted repeat did not restore the ubiquitous pattern of expression characteristic of classical class I genes. Thus, these results indicate that elements in addition to CRE region 1 in the Q10 promoter region serve to limit ubiquitous tissue expression. C1 NIAID,BIOL RESOURCES BRANCH,BLDG 4,ROOM 413,BETHESDA,MD 20892. NR 34 TC 5 Z9 5 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 AUG 15 PY 1993 VL 151 IS 4 BP 1989 EP 1997 PG 9 WC Immunology SC Immunology GA LR904 UT WOS:A1993LR90400024 PM 8345192 ER PT J AU SHIRAI, M VACCHIO, MS HODES, RJ BERZOFSKY, JA AF SHIRAI, M VACCHIO, MS HODES, RJ BERZOFSKY, JA TI PREFERENTIAL V-BETA USAGE BY CYTOTOXIC T-CELLS CROSS-REACTIVE BETWEEN 2 EPITOPES OF HIV-1 GP160 AND DEGENERATE IN CLASS-I MHC RESTRICTION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; TOXIC LYMPHOCYTES-T; RECEPTOR GENE USAGE; ANTIGEN RECEPTOR; POSITIVE SELECTION; MONOCLONAL-ANTIBODIES; MOLECULAR-GENETICS; IMPARTS REACTIVITY; ENVELOPE PROTEIN; PREDOMINANT USE AB The T cell response to HIV-1 gp160 is among the most thoroughly studied immune responses to HIV-1 products. In our previous work, the MHC class I molecule D(d) as well as H-2u, p, and q, were found to present P18 and HP53, two determinants of HIV-1 gp160, to CD8+ CTL in mice. We have studied the TCR Vbeta chain expression in CTL lines, either cross-reactive for these two peptides or specific for P18 alone, in these four different MHC haplotypes. The usage of Vbeta in T cells showing cross-reaction between these two peptides was remarkably conserved (primarily Vbeta8 family, with some use of Vbeta14) despite the extensive TCR Vbeta diversity of the non-cross-reactive CTL, which did not use Vbeta8 or 14. This correlation of Vbeta usage with fine specificity was consistent in H-2d, u, and p (p < 0.01), but not in H-2q. The correlation of Vbeta use with peptide fine specificity independent of MHC restriction was unexpected. The strong predominance of Vbeta8 family TCR was all the more surprising in view of the finding that mice bearing a genomic deletion of Vbeta8 can still produce T cells with the cross-reactive phenotype, implying that other Vbeta chains can produce this specificity. We therefore asked whether the complexes of P18 with H-2d, p, and u are recognized as identical, and observed the surprising result that H-2d, p, and u cells mutually cross-present the peptides P18 and HP53 to allogeneic CTL lines and individual clones of each of the other haplotypes, whereas none of these cross-present to H-2q CTL, nor do H-2q targets present to CTL of the other haplotypes. This degeneracy of MHC restriction is novel for class I molecules. Moreover, the observed restriction in Vbeta usage occurs only in the unique set of CTL that exhibit both peptide-cross-reactive fine specificity and MHC allogeneic cross-presentation. The observation that a strain of mice in which the Vbeta8 family is genomically deleted can still make CTL of this phenotype using another Vbeta demonstrates the plasticity of the class I MHC-restricted repertoire when the dominating receptor is not available. C1 NCI,METAB BRANCH,MOLEC IMMUNOGENESIS & VACCINE RES SECT,BLDG 10,ROOM 6B-12,BETHESDA,MD 20892. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NR 64 TC 28 Z9 28 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 AUG 15 PY 1993 VL 151 IS 4 BP 2283 EP 2295 PG 13 WC Immunology SC Immunology GA LR904 UT WOS:A1993LR90400055 PM 7688397 ER PT J AU SEKHSARIA, S GALLIN, JI LINTON, GF MALLORY, RM MULLIGAN, RC MALECH, HL AF SEKHSARIA, S GALLIN, JI LINTON, GF MALLORY, RM MULLIGAN, RC MALECH, HL TI PERIPHERAL-BLOOD PROGENITORS AS A TARGET FOR GENETIC CORRECTION OF P47(PHOX)-DEFICIENT CHRONIC GRANULOMATOUS-DISEASE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MYELOID CELLS; NEUTROPHILS; NADPH OXIDASE; RETROVIRUS; GENE TRANSFER ID HEMATOPOIETIC STEM-CELLS; RESPIRATORY BURST OXIDASE; HUMAN GM-CSF; AUTOLOGOUS TRANSPLANTATION; NADPH OXIDASE; LYMPHOCYTES-B; SUPEROXIDE GENERATION; INTERFERON-GAMMA; EXPRESSION; NEUTROPHILS AB Peripheral blood contains hematopoietic progenitors (PBHPs), which can be harvested in clinically relevant amounts by apheresis. PBHPs have been used as a source of progenitors alternative to marrow for autologous transplantation following intensive chemotherapy. We have determined culture conditions for growth and differentiation of PBHPs to the mature myeloid phenotype, which in the present study are employed to demonstrate the functional correction of an inherited disorder of myeloid cells in retrovirus-transduced human primary hematopoietic progenitors. Patients with chronic granulomatous disease (CGD) suffer from recurrent life-threatening infections because blood phagocytes fail to produce microbicidal superoxide (O2-.). One-third of the cases of CGD result from defects in the gene encoding p47phox, a cytoplasmic oxidase component required for O2-. generation. In the present study, a replication-defective retrovirus encoding p47phox was used to transduce PBHPs from patients with p47phox-deficient CGD, which resulted in significant correction of O2-. generation when PBHPs were differentiated to mature neutrophils and monocytes. This study provides a model for use of PBHPs in development of gene therapy for diseases affecting bone marrow. C1 NIAID,HOST DEF LAB,BLDG 10,ROOM 11N113,BETHESDA,MD 20892. MIT,WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. NR 42 TC 69 Z9 70 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 AUG 15 PY 1993 VL 90 IS 16 BP 7446 EP 7450 DI 10.1073/pnas.90.16.7446 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LT437 UT WOS:A1993LT43700007 PM 8395049 ER PT J AU BRINKMANN, U REITER, Y JUNG, SH LEE, B PASTAN, I AF BRINKMANN, U REITER, Y JUNG, SH LEE, B PASTAN, I TI A RECOMBINANT IMMUNOTOXIN CONTAINING A DISULFIDE-STABILIZED FV FRAGMENT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SINGLE-CHAIN-FV; PSEUDOMONAS EXOTOXIN; ESCHERICHIA-COLI; MONOCLONAL-ANTIBODIES; PROTEINS; DOMAINS; FORMS; B3 AB B3(dsFv)-PE38KDEL is a recombinant immunotoxin composed of the Fv region of monoclonal antibody B3 connected to a truncated form of Pseudomonas exotoxin (PE38KDEL), in which the unstable Fv heterodimer (composed of heavy- and light-chain variable regions) is held together and stabilized by a disulfide bond [termed disulfide-stabilized Fv (dsFv)]. A computer modeled structure of the B3(Fv), made by mutating and energy minimizing the amino acid sequence and structure of McPC603, enabled us to identify positions in conserved framework regions that ''hypothetically'' could be used for disulfide stabilization without changing the structure or affecting antigen binding. This prediction was evaluated experimentally by constructing a disulfide-linked two-chain dsFv-immunotoxin that was produced in Escherichia coli. The activity and specificity of this immunotoxin was indistinguishable from its single-chain Fv (scFv) counterpart, indicating that, as in B3(scFv), the structure of the binding region is retained in B3(dsFv). Because we introduced the stabilizing disulfide bond in between two framework residues in a position that is conserved in most Fv molecules, this method of linkage between the heavy- and light-chain variable regions should be generally applicable to construct immunotoxins and dsFv molecules using other antibodies. Furthermore, the finding that B3(dsFv) was much more stable at 37-degrees-C in human plasma than B3(scFv) indicates that dsFvs are possibly more versatile for therapeutic application than scFvs. RP BRINKMANN, U (reprint author), NCI,DIV CANC BIOL,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. RI Lee, Byungkook/E-4564-2011 OI Lee, Byungkook/0000-0002-3339-4582 NR 23 TC 174 Z9 182 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 15 PY 1993 VL 90 IS 16 BP 7538 EP 7542 DI 10.1073/pnas.90.16.7538 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LT437 UT WOS:A1993LT43700026 PM 8356052 ER PT J AU SCHERLE, P BEHRENS, T STAUDT, LM AF SCHERLE, P BEHRENS, T STAUDT, LM TI LY-GDI, A GDP-DISSOCIATION INHIBITOR OF THE RHOA GTP-BINDING PROTEIN, IS EXPRESSED PREFERENTIALLY IN LYMPHOCYTES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE RAS-RELATED GTP-BINDING PROTEINS; GDP GTP EXCHANGE INHIBITOR; LYMPHOCYTE ACTIVATION; SUBTRACTIVE HYBRIDIZATION; CDNA ID GLUTATHIONE-S-TRANSFERASE; T-CELL ACTIVATION; MOLECULAR-CLONING; REGULATORY PROTEIN; ESCHERICHIA-COLI; RAS P21; PURIFICATION; IDENTIFICATION; STIMULATION; ASSOCIATION AB The Ras-related small GTP-binding proteins are involved in diverse cellular events, including cell signaling, proliferation, cytoskeletal organization, and secretion. The interconversion of the active, GTP-bound form of the protein to the inactive, GDP-bound form is influenced by two types of regulatory proteins, those that alter the intrinsic GTPase activity of the GTP-binding protein and those that affect the rate of GDP/GTP exchange. By utilizing a subtractive hybridization approach, we have isolated a human gene encoding Ly-GDI, a protein that has striking homology to the product of a previously cloned gene, Rho-GDI, which inhibits GDP/GTP exchange on the Rho family of GTPases. In contrast to Rho-GDI, which is ubiquitously expressed, Ly-GDI is expressed only in hematopoietic tissues and predominantly in B- and T-lymphocyte cell tines. The full-length Ly-GDI cDNA encodes a 27-kDa protein which binds to RhoA and inhibits GDP dissociation from RhoA. Stimulation of T lymphocytes with phorbol ester leads to phosphorylation of Ly-GDI, suggesting an involvement of Ly-GDI in lymphocyte activation pathways. Cell type-specific regulators of the Ras-like GTP-binding proteins may provide one mechanism by which different cell types respond uniquely to signals transduced through the same cell surface receptor or may provide a way by which the GTP-binding proteins can be uniquely engaged by tissue-restricted receptors. C1 NCI,METAB BRANCH,BETHESDA,MD 20892. NR 45 TC 152 Z9 154 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 AUG 15 PY 1993 VL 90 IS 16 BP 7568 EP 7572 DI 10.1073/pnas.90.16.7568 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LT437 UT WOS:A1993LT43700032 PM 8356058 ER PT J AU KOLA, I BROOKES, S GREEN, AR GARBER, R TYMMS, M PAPAS, TS SETH, A AF KOLA, I BROOKES, S GREEN, AR GARBER, R TYMMS, M PAPAS, TS SETH, A TI THE ETS1 TRANSCRIPTION FACTOR IS WIDELY EXPRESSED DURING MURINE EMBRYO DEVELOPMENT AND IS ASSOCIATED WITH MESODERMAL CELLS INVOLVED IN MORPHOGENETIC PROCESSES SUCH AS ORGAN FORMATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DNA-BINDING; C-ETS-1 PROTOONCOGENE; ONCOGENIC ACTIVITY; PROTEIN; SEQUENCE; GENE; ACTIVATOR; PROMOTER; CONTAINS; ENHANCER AB The Ets family of genes encodes a class of transcription factors. Ets1 is predominantly expressed in the lymphoid organs of neonatal and adult mice, whereas Ets2 is expressed in every organ examined. In this study, we investigate the expression of Ets1 and Ets2 during murine embryonic development. Our data show that Ets1 expression increases in embryos after implantation and during organogenesis such that it is expressed in all the organs of day-15 embryos studied. In later fetal stages, Ets1 expression is predominant in the lymphoid tissues, brain, and organs that are undergoing branching morphogenesis (e.g., lung) but is dramatically reduced in other organs such as the stomach and intestine. In neonatal development, Ets1 is expressed only in the lymphoid organs and brain. In situ hybridization analysis demonstrates that expression of Ets1 occurs in mesenchymal cells of developing organs, in the nervous system, and in forming bone. Furthermore, expression of Ets1 is upregulated in P19 cells induced to differentiate into mesoderm-like cells. Ets2, on the other hand, is expressed in differentiated and undifferentiated P19 and F9 cells and in all organs of embryonic, neonatal, and adult mice studied. These data suggest that Ets1 plays an important role in mesodermal cells associated with morphogenetic processes such as organ formation and tissue modeling, whereas Ets2 plays a more fundamental role in cells. C1 UNIV CAMBRIDGE,DEPT HAEMATOL,CAMBRIDGE CB2 2QH,ENGLAND. NOVAGEN INC,MADISON,WI 53711. NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702. RP KOLA, I (reprint author), MONASH UNIV,CTR EARLY HUMAN DEV,MOLEC EMBRYOL & BIRTH DEFECTS LAB,CLAYTON,VIC 3168,AUSTRALIA. RI Kola, Ismail/C-5254-2013 NR 38 TC 215 Z9 218 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 AUG 15 PY 1993 VL 90 IS 16 BP 7588 EP 7592 DI 10.1073/pnas.90.16.7588 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LT437 UT WOS:A1993LT43700036 PM 7689222 ER PT J AU FELDER, CC BRILEY, EM AXELROD, J SIMPSON, JT MACKIE, K DEVANE, WA AF FELDER, CC BRILEY, EM AXELROD, J SIMPSON, JT MACKIE, K DEVANE, WA TI ANANDAMIDE, AN ENDOGENOUS CANNABIMIMETIC EICOSANOID, BINDS TO THE CLONED HUMAN CANNABINOID RECEPTOR AND STIMULATES RECEPTOR-MEDIATED SIGNAL-TRANSDUCTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ARACHIDONYLETHANOLAMIDE; ADENYLATE CYCLASE; PHOSPHOLIPASE-A2; CALCIUM; CALCIUM CURRENT ID CEREBRAL-CORTEX SLICES; BETA-GAMMA-SUBUNITS; ARACHIDONIC-ACID; ADENYLYL CYCLASE; RAT-BRAIN; CELLS; DELTA-9-TETRAHYDROCANNABINOL; RELEASE; IDENTIFICATION; PROSTAGLANDINS AB Arachidonylethanolamide (anandamide), a candidate endogenous cannabinoid ligand, has recently been isolated from porcine brain and displayed cannabinoid-like binding activity to synaptosomal membrane preparations and mimicked cannabinoid-induced inhibition of the twitch response in isolated murine vas deferens. In this study, anandamide and several congeners were evaluated as cannabinoid agonists by examining their ability to bind to the cloned cannabinoid receptor, inhibit forskolin-stimulated cAMP accumulation, inhibit N-type calcium channels, and stimulate one or more functional second messenger responses. Synthetic anandamide, and all but one congener, competed for [H-3]CP55,940 binding to plasma membranes prepared from L cells expressing the rat cannabinoid receptor. The ability of anandamide to activate receptor-mediated signal transduction was evaluated in Chinese hamster ovary (CHO) cells expressing the human cannabinoid receptor (HCR, termed CHO-HCR cells) and compared to control CHO cells expressing the muscarinic m5 receptor (CHOm5 cells). Anandamide inhibited forskolin-stimulated cAMP accumulation in CHO-HCR cells, but not in CHOm5 cells, and this response was blocked with pertussis toxin. N-type calcium channels were inhibited by anandamide and several active congeners in N18 neuroblastoma cells. Anandamide stimulated arachidonic acid and intracellular calcium release in both CHOm5 and CHO-HCR cells and had no effect on the release of inositol phosphates or phosphatidylethanol, generated after activation of phospholipase C and D, respectively. Anandamide appears to exhibit the essential criteria required to be classified as a cannabinoid/anandamide receptor agonist and shares similar nonreceptor effects on arachidonic acid and intracellular calcium release as other cannabinoid agonists. C1 NIMH,CELL BIOL LAB,BLDG 36,ROOM 3A-15,BETHESDA,MD 20892. NIMH,ANALYT BIOCHEM SECT,CLIN SCI LAB,BETHESDA,MD 20892. UNIV WASHINGTON,DEPT PHYSIOL & BIOPHYS,SEATTLE,WA 98195. RI Mackie, Kenneth/B-7358-2011; Mackie, Ken/E-3715-2013 OI Mackie, Ken/0000-0001-8501-6199 FU NINDS NIH HHS [NS01588] NR 33 TC 398 Z9 402 U1 1 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 AUG 15 PY 1993 VL 90 IS 16 BP 7656 EP 7660 DI 10.1073/pnas.90.16.7656 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LT437 UT WOS:A1993LT43700050 PM 8395053 ER PT J AU GARRITSEN, A VANGALEN, PJM SIMONDS, WF AF GARRITSEN, A VANGALEN, PJM SIMONDS, WF TI THE N-TERMINAL COILED-COIL DOMAIN OF BETA IS ESSENTIAL FOR GAMMA-ASSOCIATION - A MODEL FOR G-PROTEIN BETA-GAMMA-SUBUNIT INTERACTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ROD OUTER SEGMENTS; ALPHA-SUBUNIT; TRANSDUCIN; ANTIBODIES; MEMBRANE; STIMULATION; SPECIFICITY; PRENYLATION; MECHANISM; RECEPTORS AB We have identified the N terminus of the beta subunit as an essential domain for G-protein betagamma assembly. A C-terminal fragment, beta1-(130-340), fails to bind gamma unless coexpressed with the complementary N-terminal fragment, beta1-(1-129). Deletion of the N-terminal 33 residues of beta1, a region identified by computer algorithm to favor coiled-coil formation, abolishes gamma2 association. On the basis of these findings, we propose a coiled-coil model of betagamma interaction and refine this by computer-assisted molecular modeling. The model is tested by further mutagenesis: reversing the charge of residues in beta1 that are hypothesized to be involved in interhelical salt bridges precludes gamma association. Insertions in the coiled-coil region, which disrupt the proposed hydrophobic interface, prevent gamma association. This structural basis for betagamma dimerization provides a starting point for the design of beta and gamma mutants that can be used to map regions in betagamma critical for interactions with the alpha subunit, receptors, and effectors. C1 NIDDKD,MOLEC PATHOPHYSIOL BRANCH,BLDG 10,ROOM 8C-101,BETHESDA,MD 20892. NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. NR 36 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 AUG 15 PY 1993 VL 90 IS 16 BP 7706 EP 7710 DI 10.1073/pnas.90.16.7706 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LT437 UT WOS:A1993LT43700060 PM 8356073 ER PT J AU THOMAS, DC KUNKEL, TA AF THOMAS, DC KUNKEL, TA TI REPLICATION OF UV-IRRADIATED DNA IN HUMAN CELL-EXTRACTS - EVIDENCE FOR MUTAGENIC BYPASS OF PYRIMIDINE DIMERS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ESCHERICHIA-COLI; INDUCED MUTATIONS; MAMMALIAN-CELLS; SHUTTLE VECTOR; STRAND SPECIFICITY; ULTRAVIOLET-LIGHT; CIS-SYN; HUMAN FIBROBLASTS; THYMINE DIMERS; MONKEY CELLS AB We have examined the efficiency and fidelity of simian virus 40-origin-dependent replication of UV-irradiated double-stranded DNA in extracts of human cells. Using as a mutational target the a-complementation domain of the Escherichia coli lacZ gene in bacteriophage M13mp2 DNA, replication of undamaged DNA in HeLa cell extracts was highly accurate, whereas replication of DNA irradiated with UV light (280-320 nm) was both less efficient and less accurate. Replication was inhibited by irradiation in a dose-dependent manner. Nonetheless, covalently closed, monomer-length circular products were generated that were resistant to digestion by Dpn I, showing that they resulted from semiconservative replication. These products were incised by T4 endonuclease V, whereas the undamaged replication products were not, suggesting that pyrimidine dimers were bypassed during replication. When replicated, UV-irradiated DNA was used to transfect an E. coli alpha-complementation host strain to score mutant M13mp2 plaques, the mutant plaque frequency was substantially higher than that obtained with either unirradiated, replicated DNA, or unreplicated, UV-irradiated DNA. Both the increased mutagenicity and the inhibition of replication associated with UV irradiation were reversed by treatment of the irradiated DNA with photolyase before replication. Sequence analysis of mutants resulting from replication of UV-irradiated DNA demonstrated that most mutants contained C --> T transition errors at dipyrimidine sites. A few mutants contained 1-nt frameshift errors or tandem double CC --> TT substitutions. The data are consistent with the interpretation that pyrimidine dimers are bypassed during replication by the multiprotein replication apparatus in human cell extracts and that this bypass is mutagenic primarily via misincorporation of dAMP opposite a cytosine (or uracil) in the dimer. C1 NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. NR 56 TC 50 Z9 50 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 15 PY 1993 VL 90 IS 16 BP 7744 EP 7748 DI 10.1073/pnas.90.16.7744 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LT437 UT WOS:A1993LT43700068 PM 8356079 ER PT J AU THEUER, CP BUCHNER, J FITZGERALD, D PASTAN, I AF THEUER, CP BUCHNER, J FITZGERALD, D PASTAN, I TI THE N-TERMINAL REGION OF THE 37-KDA TRANSLOCATED FRAGMENT OF PSEUDOMONAS EXOTOXIN-A ABORTS TRANSLOCATION BY PROMOTING ITS OWN EXPORT AFTER MICROSOMAL MEMBRANE INSERTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SIGNAL RECOGNITION PARTICLE; ENDOPLASMIC-RETICULUM; PROTEIN TRANSLOCATION; PRESECRETORY PROTEINS; RECOMBINANT TOXINS; RECEPTOR; AERUGINOSA; PEPTIDASE; CLEAVAGE; TRANSPORT AB The 37-kDa C-terminal fragment of Pseudomonas exotoxin A (PE; termed PE37 and composed of aa 280-613 of PE) translocates to the cell cytosol to cause cell death. PE37 requires a C-terminal endoplasmic reticulum retention sequence to be cytotoxic, indicating that the toxin may translocate to the cytosol from the endoplasmic reticulum. We show here that the N-terminal region of nascent PE37 can be inserted into the membrane of canine pancreatic microsomes by the preprocecropin signal sequence but then is exported or released from microsomes. The 34 N-terminal amino acids of the toxin fragment are sufficient to arrest translocation and prevent the microsomal accumulation of nascent chains that otherwise are sequestered into microsomes. These data support a role for the N-terminal region of PE37 in the translocation of the toxin from the endoplasmic reticulum to the cytosol in mammalian cells. C1 NCI,DIV CANC BIOL,MOLEC BIOL LAB,BLDG 37,ROOM 4E16,BETHESDA,MD 20892. RI Buchner, Johannes/A-2651-2010 NR 33 TC 47 Z9 50 U1 1 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 AUG 15 PY 1993 VL 90 IS 16 BP 7774 EP 7778 DI 10.1073/pnas.90.16.7774 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LT437 UT WOS:A1993LT43700074 PM 8356083 ER PT J AU BENZING, WC BRADY, DR MUFSON, EJ ARMSTRONG, DM AF BENZING, WC BRADY, DR MUFSON, EJ ARMSTRONG, DM TI EVIDENCE THAT TRANSMITTER-CONTAINING DYSTROPHIC NEURITES PRECEDE THOSE CONTAINING PAIRED HELICAL FILAMENTS WITHIN SENILE PLAQUES IN THE ENTORHINAL CORTEX OF NONDEMENTED ELDERLY AND ALZHEIMERS-DISEASE PATIENTS SO BRAIN RESEARCH LA English DT Article DE ALZ-50; AMYLOID BETA-PROTEIN; IMMUNOCYTOCHEMISTRY; NEUROPEPTIDE; PAIRED-HELICAL FILAMENT; PATHOGENESIS; SENILE PLAQUE ID AGED HUMAN BRAIN; NEUROFIBRILLARY TANGLES; DOWNS-SYNDROME; INTELLECTUAL STATUS; SYNAPTIC PATHOLOGY; BETA-A4 DEPOSITS; TAU-PROTEINS; SUBSTANCE-P; LEWY BODIES; DEMENTIA AB Within the amygdala of elderly subjects and patients with Alzheimer's disease (AD), we recently found evidence suggesting amyloid beta-protein (AbetaP) deposition occurs before the appearance of dystrophic neurites. Moreover, these data suggested dystrophic neurites initially lack evidence of cytoskeletal pathology although with time and further maturation, the dystrophic neurites display an altered cytoskeleton as evidenced by their immunoreactivity to Alz-50 and paired-helical filaments (PHF). These findings are of particular relevance to our understanding of the sequence of pathologic events in AD and thus it has become important to determine whether these events are unique to the amygdala or are representative of a more general pattern which can be found throughout the brain. Using a battery of antibodies to markers that are characteristic of AD pathology (i.e., AbetaP, PHF, and Alz-50), three peptidergic neurotransmitters (neurotensin, somatostatin, and substance P), and one neurotransmitter biosynthetic enzyme (choline acetyltransferase), we examined the entorhinal cortex (EC) of three groups of subjects (AD, normal elderly, and a group of nondemented elderly with numerous senile plaques). The EC was studied, in part, because it is well recognized as a brain region displaying severe and, most importantly, early pathologic changes. Like the amygdala, we found evidence that amyloid beta-protein immunoreactive (AbetaP-IR) and thioflavine-S-positive senile plaques occur within the EC prior to the appearance of transmitter-, Alz-50-, or PHF-immunoreactive dystrophic neurites. We also observed transmitter-immunoreactive dystrophic neurites in the absence of Alz-50 or PHF-immunolabeled dystrophic neurites and transmitter- and Alz-50-IR dystrophic neurites in the absence of those containing PHF. Collectively, these findings were similar to those seen within the amygdala and thus reinforced the concept that AbetaP deposition is the primary event in plaque pathology, and this deposition is subsequently followed by the appearance of dystrophic neurites which retain their transmitter phenotype yet lack an altered cytoskeleton. With time, these dystrophic neurites develop cytoskeletal alterations and become immunoreactive to Alz-50 and PHF. C1 GEORGETOWN UNIV,GEORGETOWN INST NEUROSCI,FIDIA,3900 RESERVOIR RD,WASHINGTON,DC 20007. NIA,NEUROSCI LAB,BETHESDA,MD 20892. RUSH ST LUKE PRESBYTERIAN MED CTR,DEPT NEUROL,CHICAGO,IL 60612. FU NIA NIH HHS [AG08206, AG05344, AG10688] NR 69 TC 27 Z9 27 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 13 PY 1993 VL 619 IS 1-2 BP 55 EP 68 DI 10.1016/0006-8993(93)91595-J PG 14 WC Neurosciences SC Neurosciences & Neurology GA LQ511 UT WOS:A1993LQ51100006 PM 7690677 ER PT J AU POLTORAK, M WILLIAMS, JR FREED, WJ AF POLTORAK, M WILLIAMS, JR FREED, WJ TI DEGRADATION FRAGMENTS OF L1-ANTIGEN ENHANCE TYROSINE HYDROXYLASE-IMMUNOREACTIVE NEURITE OUTGROWTH IN MESENCEPHALIC CELL-CULTURE SO BRAIN RESEARCH LA English DT Article DE CELL ADHESION MOLECULE; SUBSTRATE; NEURITE OUTGROWTH; TYROSINE HYDROXYLASE; DOPAMINE; CEREBROSPINAL FLUID; TROPHIC FACTOR ID ADRENAL-MEDULLA GRAFTS; ADHESION MOLECULE L1; DOPAMINERGIC-NEURONS; BIOCHEMICAL-CHARACTERIZATION; L1/NG-CAM EXPRESSION; EXTRACELLULAR-MATRIX; NERVOUS-SYSTEM; SCIATIC-NERVE; N-CAM; GROWTH AB The L1 antigen has been implicated in adhesion events controlling axonal elongation during formation of major fiber tracts, and promotes neurite outgrowth in culture. It is possible that injury of brain tissue causes neuronal surface molecules such as L1 antigen to be shed, and degradation fragments may therefore be present adjacent to the damage. These Ll fragments might then influence regeneration or injury-induced growth. We have evaluated neurite outgrowth from tyrosine hydroxylase-positive (TH+) E13 mesencephalic neurons grown in vitro on a substrate of mouse Ll antigen and on L1 degradation fragments separated by molecular weight. Mouse myelin-associated glycoprotein (MAG), laminin, poly-D-lysine, and fetal calf serum served as control substrates. L1 antibodies were added to one set of cultures (experimental), and compared to control cultures containing normal rabbit serum. After 3 days in vitro, the cultures were stained using an antibody against TH, and the length of the TH+ neurites was measured by computer-assisted image analysis in a double-blind fashion. TH+ neurites were significantly longer when grown on Ll antigen, as well as on Ll degradation fragments, as compared to the control substrates. As compared to control normal rabbit serum, L1 antibodies eliminated the neurite-promoting effect of both the Ll substrate and the Ll degradation products. In addition, Ll substrates promoted clustering of TH+ cells and the formation of loose bundles of TH+ neurites. It is suggested that the L1 substrates influence TH-immunoreactive neurite outgrowth, at least partially, through indirect effects on glial cells. OUT data indicate that the presence of L1 fragments in vivo might influence regeneration or synaptic restructuring. Moreover, we speculate that the studies of large proteins as substrates in cell culture may be influenced by protein instability, and that some studies may have examined the functions of protein fragments rather then intact proteins. RP POLTORAK, M (reprint author), NIMH,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,PRECLIN NEUROSCI SECT,2700 MARTIN LUTHER KING AVE,WASHINGTON,DC 20032, USA. NR 37 TC 4 Z9 4 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 AUG 13 PY 1993 VL 619 IS 1-2 BP 255 EP 262 DI 10.1016/0006-8993(93)91619-4 PG 8 WC Neurosciences SC Neurosciences & Neurology GA LQ511 UT WOS:A1993LQ51100030 PM 8104088 ER PT J AU CHUNG, JH WHITELEY, M FELSENFELD, G AF CHUNG, JH WHITELEY, M FELSENFELD, G TI A 5' ELEMENT OF THE CHICKEN BETA-GLOBIN DOMAIN SERVES AS AN INSULATOR IN HUMAN ERYTHROID-CELLS AND PROTECTS AGAINST POSITION EFFECT IN DROSOPHILA SO CELL LA English DT Article ID LOCUS-CONTROL REGION; DOMINANT CONTROL REGION; TOPOISOMERASE-II SITES; GENE-EXPRESSION; WHITE GENE; HYPERSENSITIVE SITES; ACTIVATION REGION; SENSITIVE DOMAIN; CHROMATIN DOMAIN; TRANSGENIC MICE AB We have characterized an element near the 5' boundary of the chicken beta-globin domain that insulates a reporter gene from the activating effects of a nearby beta-globin locus control region (5'HS2) when assayed in the human erythroid cell line K562. We show that the insulation mechanism is directional, that it operates at the level of transcription, and that it involves the alteration of chromatin structure over the promoter of the gene. The insulator has no significant stimulatory or inhibitory effects of its own. In transgenic Drosophila, the insulator protects the white minigene from position effects. The action of the insulator thus is not restricted to erythroid or mammalian cells, suggesting that such elements may serve an important and widely distributed function in the organization of chromatin structure. C1 US FDA,DIV CELLULAR & GENE THERAPY,BETHESDA,MD 20892. RP CHUNG, JH (reprint author), NIH,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 51 TC 687 Z9 699 U1 1 U2 17 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD AUG 13 PY 1993 VL 74 IS 3 BP 505 EP 514 DI 10.1016/0092-8674(93)80052-G PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LT739 UT WOS:A1993LT73900012 PM 8348617 ER PT J AU VANMEERWIJK, JPM GERMAIN, RN AF VANMEERWIJK, JPM GERMAIN, RN TI DEVELOPMENT OF MATURE CD8+ THYMOCYTES - SELECTION RATHER THAN INSTRUCTION SO SCIENCE LA English DT Article ID T-CELL RECEPTOR; THYMIC SELECTION; SEQUENTIAL APPEARANCE; SUBLETHAL IRRADIATION; NEGATIVE SELECTION; PRECURSOR CELLS; LYMPHOCYTES-T; MOUSE THYMUS; STEM-CELLS; CD4 AB The role of major histocompatibility complex (MHC) molecules in T cell differentiation was investigated by comparison of thymocyte subpopulations in wild-type mice and beta2-microglobulin (beta2M) mutant mice deficient in MHC class I expression and mature CD8+ cells. On the basis of surface markers, glucocorticoid resistance, in vitro differentiation capacity, and absence in beta2M-/- mice, CD4(intermediate)CD8hi cells with high expression of alphabeta T cell receptor (TCRalphabeta) were identified as having been positively selected by MHC class I for development into mature CD8+ T cells. Activated CD4(int)CD8hi cells bearing intermediate rather than high amounts of TCR were present in both wild-type and beta2M-/- animals. These data suggest that recognition of MHC class I molecules is required for full maturation to CD8+ T cells, but not for receptor-initiated commitment to the CD8+ lineage, consistent with a stochastic (selection) model of thymocyte development. C1 NIAID,IMMUNOL LAB,LYMPHOCYTE BIOL SECT,BETHESDA,MD 20892. RI van Meerwijk, Joost/K-1345-2014 NR 47 TC 98 Z9 98 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 AUG 13 PY 1993 VL 261 IS 5123 BP 911 EP 915 DI 10.1126/science.8102208 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LR897 UT WOS:A1993LR89700038 PM 8102208 ER PT J AU LOVE, PE SHORES, EW JOHNSON, MD TREMBLAY, ML LEE, EJ GRINBERG, A HUANG, SP SINGER, A WESTPHAL, H AF LOVE, PE SHORES, EW JOHNSON, MD TREMBLAY, ML LEE, EJ GRINBERG, A HUANG, SP SINGER, A WESTPHAL, H TI T-CELL DEVELOPMENT IN MICE THAT LACK THE ZETA-CHAIN OF THE T-CELL ANTIGEN RECEPTOR COMPLEX SO SCIENCE LA English DT Article ID ETA-CHAIN; SIGNAL TRANSDUCTION; MONOCLONAL-ANTIBODY; TRANSGENIC MICE; EXPRESSION; THYMOCYTES; CD4; MUTATIONS; FAMILY; TCR AB The zeta subunit of the T cell antigen receptor complex is required for targeting nascent receptor complexes to the cell surface and for receptor-mediated signal transduction. To examine the significance of the zeta subunit in T cell development, mice deficient for zeta expression were generated by gene targeting. These zeta-/- mice had few CD4+CD8+ thymocytes, and the generation of CD4+ and CD8+ single positive T cells was impaired but not completely abrogated. Peripheral T cells were present but were unusual in that they expressed small amounts of CD5 and few T cell receptors. Thus, zeta chain expression influences thymocyte differentiation but is not absolutely required for the generation of single positive T cells. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RP LOVE, PE (reprint author), NICHHD,MAMMALIAN GENES & DEV LAB,BLDG 6B,ROOM 210,BETHESDA,MD 20892, USA. NR 33 TC 189 Z9 189 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 AUG 13 PY 1993 VL 261 IS 5123 BP 918 EP 921 DI 10.1126/science.7688481 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LR897 UT WOS:A1993LR89700040 PM 7688481 ER PT J AU BERZOFSKY, JA AF BERZOFSKY, JA TI EPITOPE SELECTION AND DESIGN OF SYNTHETIC VACCINES - MOLECULAR APPROACHES TO ENHANCING IMMUNOGENICITY AND CROSS-REACTIVITY OF ENGINEERED VACCINES SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID CLASS-I MOLECULES; HIV-SEROPOSITIVE INDIVIDUALS; ANTIGEN-BINDING SITE; T-CELL RECOGNITION; PEPTIDE BINDING; LYMPHOCYTES-T; MHC; SEQUENCE; IDENTIFICATION; PREDICTION RP BERZOFSKY, JA (reprint author), NCI, METAB BRANCH, MOLEC IMMUNOGENET & VACCINE RES SECT, BLDG 10, ROOM 6B12, BETHESDA, MD 20892 USA. NR 48 TC 1 Z9 1 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PD AUG 12 PY 1993 VL 690 BP 256 EP 264 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LX021 UT WOS:A1993LX02100027 ER PT J AU GRUBER, J COLE, JS AF GRUBER, J COLE, JS TI VACCINES FOR HUMAN CANCERS OF VIRAL ETIOLOGY SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID ANTIGEN PRESENTATION; ENVELOPE PROTEIN; LYMPHOCYTES-T; TUMOR; CELLS; B72.3; IDENTIFICATION; GLYCOPROTEIN; GENERATION; INDUCTION RP GRUBER, J (reprint author), NCI, BETHESDA, MD 20892 USA. NR 24 TC 0 Z9 0 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PD AUG 12 PY 1993 VL 690 BP 311 EP 321 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LX021 UT WOS:A1993LX02100032 ER PT J AU SOGN, JA FINERTY, JF HEATH, AK SHEN, GLC AUSTIN, FC AF SOGN, JA FINERTY, JF HEATH, AK SHEN, GLC AUSTIN, FC TI CANCER VACCINES - THE PERSPECTIVE OF THE CANCER IMMUNOLOGY BRANCH, NCI SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID TUMOR-NECROSIS-FACTOR; T-CELLS; HUMAN-MELANOMA; GROWTH-FACTOR; LYMPHOCYTES; ANTIGENS; INTERLEUKIN-4; RECOGNITION; MACROPHAGES; GENERATION RP SOGN, JA (reprint author), NCI, DIV CANC BIOL DIAGNOSIS & CTR, CANC IMMUNOL BRANCH, BETHESDA, MD 20892 USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PD AUG 12 PY 1993 VL 690 BP 322 EP 330 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LX021 UT WOS:A1993LX02100033 ER PT J AU KANTOR, J ABRAMS, S IRVINE, K SNOY, P KAUFMAN, H SCHLOM, J AF KANTOR, J ABRAMS, S IRVINE, K SNOY, P KAUFMAN, H SCHLOM, J TI SPECIFIC IMMUNOTHERAPY USING A RECOMBINANT VACCINIA VIRUS EXPRESSING HUMAN CARCINOEMBRYONIC ANTIGEN SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID GENE C1 US FDA, BETHESDA, MD 20892 USA. RP KANTOR, J (reprint author), NCI, TUMOR IMMUNOL & BIOL LAB, BETHESDA, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PD AUG 12 PY 1993 VL 690 BP 370 EP 373 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LX021 UT WOS:A1993LX02100047 ER PT J AU FRANCIS, CL RYAN, TA JONES, BD SMITH, SJ FALKOW, S AF FRANCIS, CL RYAN, TA JONES, BD SMITH, SJ FALKOW, S TI RUFFLES INDUCED BY SALMONELLA AND OTHER STIMULI DIRECT MACROPINOCYTOSIS OF BACTERIA SO NATURE LA English DT Article ID EPIDERMAL GROWTH-FACTOR; CARCINOMA-CELLS A-431; CULTURED-MAMMALIAN-CELLS; FACTOR RECEPTOR; CYTOSKELETAL CHANGES; EPITHELIAL-CELLS; TYROSINE KINASE; KB-CELLS; MEMBRANE; TYPHIMURIUM AB RUFFLES are specialized plasma membrane ultrastructures of mammalian cells thought to be integral to growth, development and locomotion1-4. Induced by growth factors5-8, mitogens9 or oncogene expression10,11, ruffles are sites of filamentous actin rearrangement7,8 and are temporally associated with enhanced pinocytosis10,12. But the function of ruffles, their mechanism of induction and their role in pinocytosis are not understood. We have observed formation of structures resembling ruffles associated with the site of entry of invasive Salmonella typhimurium13. Here we report that ruffles elicited by invasive Salmonella directly mediate internalization of non-invasive bacteria in a macropinocytotic fashion, a phenomenon we term 'passive entry'. Furthermore, ruffles induced in the absence of Salmonella also facilitate passive entry. We present evidence that ruffles, common to many signalling events, comprise the macropinocytotic machinery mediating pinocytosis and are subverted by Salmonella so as to enter mammalian cells. C1 STANFORD UNIV,DEPT MOLEC & CELLULAR PHYSIOL,STANFORD,CA 94305. NIH,ROCKY MT LAB,HAMILTON,MT 59840. RP FRANCIS, CL (reprint author), STANFORD UNIV,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305, USA. OI Ryan, Timothy/0000-0003-2533-9548 NR 30 TC 325 Z9 328 U1 0 U2 14 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD AUG 12 PY 1993 VL 364 IS 6438 BP 639 EP 642 DI 10.1038/364639a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LR771 UT WOS:A1993LR77100056 PM 8350922 ER PT J AU HAVERKOS, HW AF HAVERKOS, HW TI REPORTED CASES OF AIDS - AN UPDATE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP HAVERKOS, HW (reprint author), NIDA,ROCKVILLE,MD 20857, USA. NR 1 TC 10 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 AUG 12 PY 1993 VL 329 IS 7 BP 511 EP 511 DI 10.1056/NEJM199308123290719 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LR443 UT WOS:A1993LR44300035 PM 8332172 ER PT J AU PERLMAN, JA BRAWLEY, OW FORD, LG KRAMER, BS AF PERLMAN, JA BRAWLEY, OW FORD, LG KRAMER, BS TI VASECTOMY AND INCREASED RISK OF PROSTATE-CANCER SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP PERLMAN, JA (reprint author), NCI,BETHESDA,MD 20892, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 11 PY 1993 VL 270 IS 6 BP 706 EP 707 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA LQ338 UT WOS:A1993LQ33800013 PM 8336364 ER PT J AU STRAUS, SE AF STRAUS, SE TI ACUTE HERPES-ZOSTER - SYMPATHETIC-NERVE BLOCK UNSUPPORTED BY PROSPECTIVE TRIAL - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP STRAUS, SE (reprint author), NIAID,BETHESDA,MD 20892, USA. NR 0 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 AUG 11 PY 1993 VL 270 IS 6 BP 710 EP 710 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LQ338 UT WOS:A1993LQ33800024 ER PT J AU NEATON, JD GRIMM, RH PRINEAS, RJ STAMLER, J GRANDITS, GA ELMER, PJ CUTLER, JA FLACK, JM SCHOENBERGER, JA MCDONALD, R LEWIS, CE LIEBSON, PR AF NEATON, JD GRIMM, RH PRINEAS, RJ STAMLER, J GRANDITS, GA ELMER, PJ CUTLER, JA FLACK, JM SCHOENBERGER, JA MCDONALD, R LEWIS, CE LIEBSON, PR TI TREATMENT OF MILD HYPERTENSION STUDY - FINAL RESULTS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID LEFT-VENTRICULAR MASS; CORONARY HEART-DISEASE; HIGH BLOOD-PRESSURE; RANDOMIZED CONTROLLED TRIAL; FACTOR INTERVENTION TRIAL; ST-SEGMENT DEPRESSION; AMBULATORY ELECTROCARDIOGRAPHY; MYOCARDIAL ISCHEMIA; PRIMARY PREVENTION; DRUG-THERAPY AB Objective.-To compare six antihypertensive interventions for the treatment of mild hypertension. Design.-Randomized, double-blind, placebo-controlled clinical trial. Setting.-Four hypertension screening and treatment centers in the United States. Participants.-Hypertensive men and women, aged 45 to 69 years, with diastolic blood pressure less than 100 mm Hg. Intervention.-Sustained nutritional-hygienic advice to all participants to reduce weight, dietary sodium intake, and alcohol intake, and increase physical activity. Participants were randomly allocated to take (1) placebo (n=234); (2) chlorthalidone (n=136); (3) acebutolol (n=132); (4) doxazosin mesylate (n=134); (5) amlodipine maleate (n=131); or (6) enalapril maleate (n=135). Main Outcome Measures.-Blood pressure, quality of life, side effects, blood lipid levels and analysis of other serum components, echocardiographic and electrocardiographic changes, and incidence of cardiovascular events over an average of 4.4 years of follow-up. Results.-Blood pressure reductions were sizable in all six groups, and were significantly greater for participants assigned to drug treatment than placebo (-15.9 vs -9.1 mm Hg for systolic blood pressure and -12.3 vs -8.6 mm Hg for diastolic blood pressure; P<.0001). After 4 years, 59% of participants assigned to placebo and 72% of participants given drug treatment continued on their initial medication as mono-therapy. A smaller percentage of participants assigned to the drug-treatment groups died or experienced a major nonfatal cardiovascular event than those assigned to the placebo group (5.1 % vs 7.3%; P=.21). After including other clinical events, the percentage of participants affected was 11.1 % for those in the drug-treatment groups and 16.2% for those in the placebo group (P=.03). Incidence rates of most resting electrocardiographic abnormalities were lower and quality of life was improved more for those assigned to drug-treatment groups rather than the placebo group. Differences among the five drug treatments did not consistently favor one group in terms of regression of left ventricular mass, blood lipid levels, and other outcome measures. Conclusions.-As an initial regimen, drug treatment in combination with nutritional-hygienic intervention was more effective in preventing cardiovascular and other clinical events than was nutritional-hygienic treatment alone. Drug-treatment group differences were minimal. Pending results from large-scale clinical trials to evaluate drug treatments for their effect on cardiovascular clinical events, these findings support the recommendations of the new fifth Joint National Committee report regarding treatment choices for people with stage 1 (''mild'') hypertension. C1 UNIV ALABAMA,DIV GEN & PREVENT MED,BIRMINGHAM,AL 35294. UNIV PITTSBURGH,SCH MED,PITTSBURGH,PA 15261. UNIV MINNESOTA,SCH MED,DIV GEN MED,MINNEAPOLIS,MN 55455. NORTHWESTERN UNIV,DEPT COMMUNITY HLTH & PREVENT MED,CHICAGO,IL 60611. NHLBI,PREVENT & DEMONSTRAT RES BRANCH,BETHESDA,MD 20892. UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,MINNEAPOLIS,MN 55414. UNIV MINNESOTA,SCH MED,DIV CARDIOVASC DIS,MINNEAPOLIS,MN 55455. UNIV MIAMI,DEPT EPIDEMIOL & PUBL HLTH,CORAL GABLES,FL 33124. RUSH PRESBYTERIAN ST LUKES MED CTR,CARDIOL SECT,CHICAGO,IL 60612. RUSH PRESBYTERIAN ST LUKES MED CTR,DEPT PREVENT MED,CHICAGO,IL 60612. RP NEATON, JD (reprint author), UNIV MINNESOTA,SCH PUBL HLTH,DIV BIOSTAT,2221 UNIV AVE SE,ROOM 200,MINNEAPOLIS,MN 55414, USA. FU NHLBI NIH HHS [R01-HL34767] NR 83 TC 761 Z9 779 U1 4 U2 25 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 AUG 11 PY 1993 VL 270 IS 6 BP 713 EP 724 DI 10.1001/jama.270.6.713 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA LQ338 UT WOS:A1993LQ33800026 PM 8336373 ER PT J AU HONGYO, T BUZARD, GS CALVERT, RJ WEGHORST, CM AF HONGYO, T BUZARD, GS CALVERT, RJ WEGHORST, CM TI COLD SSCP - A SIMPLE, RAPID AND NONRADIOACTIVE METHOD FOR OPTIMIZED SINGLE-STRAND CONFORMATION POLYMORPHISM ANALYSES SO NUCLEIC ACIDS RESEARCH LA English DT Article ID POLYMERASE CHAIN-REACTION; PCR-SSCP; NONISOTOPIC SSCP; MUTATIONS AB A rapid (< 2.5 hrs) method for single-strand conformation polymorphism (SSCP) analysis of PCR products that allows the use of ethidium bromide staining is described. PCR products ranging in size from 117 to 256 bp were evaluated for point mutations and polymorphisms by 'cold SSCP' in commercially available pre-cast polyacrylamide mini-gels. Several electrophoretic parameters (running temperature, buffers, denaturants, DNA concentration, and gel polyacrylamide concentration) were found to influence the degree of strand separation and appeared to be PCR fragment specific. Use of the 'cold' SSCP technique and the mini-gel format allowed us to readily optimize the electrophoretic conditions for each PCR fragment. This greatly increased our ability to detect polymorphisms compared to conventional, radioisotope-labeled 'hot' SSCP, typically run under two standard temperature conditions. Excellent results have been obtained in resolving mutant PCR fragments from human p53 exons 5 through 8, human HLA-DOA, human K-ras exons 1 and 2, and rat K-ras exon 3. Polymorphisms could be detected when mutant DNA comprised as little as 3% of the total gene copies in a PCR mixture. Compared to standard 'hot' SSCP, this novel non-isotopic method has additional advantages of dramatically increased speed, precise temperature control, reproducibility, and easily and inexpensively obtainable reagents and equipment. This new method also lacks the safety and hazardous waste management concerns associated with radioactive methods. C1 NCI,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. PRI DYN CORP,FCRDC,BCDP,FREDERICK,MD 21702. US FDA,OFF SPECIAL NUTR,LAUREL,MD. NR 21 TC 321 Z9 329 U1 0 U2 4 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 AUG 11 PY 1993 VL 21 IS 16 BP 3637 EP 3642 DI 10.1093/nar/21.16.3637 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LT965 UT WOS:A1993LT96500005 PM 8367279 ER PT J AU BROWN, PC THORGEIRSSON, SS SILVERMAN, JA AF BROWN, PC THORGEIRSSON, SS SILVERMAN, JA TI CLONING AND REGULATION OF THE RAT MDR2 GENE SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MULTIDRUG-RESISTANCE GENE; P-GLYCOPROTEIN GENE; BACTERIAL TRANSPORT PROTEINS; HAMSTER OVARY CELLS; CHINESE-HAMSTER; MONOCLONAL-ANTIBODIES; HEPATOCYTE CULTURES; CHLORIDE CHANNEL; ATP HYDROLYSIS; EXPRESSION AB We have cloned the complete cDNA encoding the rat mdr2 gene by a combination of library screening and the polymerase chain reaction. The sequence of rat mdr2 cDNA is highly similar to other members of the mdr gene family but the initiation of transcription, tissue distribution and regulation of expression of rat mdr2 diverge from the other isoforms. Primer extension analysis showed rat mdr2 mRNA to have a major transcription start point at -277 and a minor one at approximately -518. We constructed gene specific probes for rat mdr2 and mdr1b and compared the expression patterns of these two genes. The highest expression of mdr2 mRNA was in the muscle, heart, liver and spleen. Both mdr2 and 1b mRNA levels were elevated in the livers of rats treated with CCl4 or following partial hepatectomies although the time course of induction of each gene differed. Mdr1b increased by 12 to 24 hours while mdr2 did not increase until 48 hours. Treatment of isolated hepatocytes or RC3 cells with cycloheximide did not effect mdr2 mRNA. In contrast, mdr1b expression was increased. These data suggest that rat mdr2, unlike mdr1b, is not regulated by a negative trans-acting protein factor. C1 NIGMS,BETHESDA,MD 20892. RP BROWN, PC (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BLDG 37,ROOM 3C28,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 62 TC 63 Z9 64 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 AUG 11 PY 1993 VL 21 IS 16 BP 3885 EP 3891 DI 10.1093/nar/21.16.3885 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LT965 UT WOS:A1993LT96500040 PM 8103593 ER PT J AU AULAKH, CS HILL, JL MURPHY, DL AF AULAKH, CS HILL, JL MURPHY, DL TI ATTENUATION OF HYPERCORTISOLEMIA IN FAWN-HOODED RATS BY ANTIDEPRESSANT DRUGS SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Note DE IMIPRAMINE; CLOMIPRAMINE; CLORGYLINE; CORTICOSTERONE; ACTH (ADRENOCORTICOTROPIN); FAWN-HOODED RAT ID STRESS; BRAIN; CORTICOSTERONE; DEPRESSION; SUBSENSITIVITY; RESPONSES; INCREASES; RECEPTORS; HORMONE; WISTAR AB Long-term (21 days) treatment with imipramine, clomipramine (tricyclic antidepressants) and clorgyline (monoamine-oxidase type A inhibiting antidepressant) produced significant decreases in plasma corticosterone levels in fawn-hooded (FH) rats. In contrast, plasma adrenocorticotropic hormone (ACTH) levels were not altered by chronic imipramine or clorgyline treatment but were significantly higher in chronic clomipramine-treated FH rats. These findings demonstrate a differential effect of chronic antidepressant treatment on plasma ACTH and corticosterone concentrations in FH rats and, furthermore, support the results of earlier studies suggesting that the FH rat strain may represent a genetic model of depression. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NR 16 TC 30 Z9 30 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD AUG 10 PY 1993 VL 240 IS 1 BP 85 EP 88 DI 10.1016/0014-2999(93)90550-2 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LT406 UT WOS:A1993LT40600013 PM 8405126 ER PT J AU DAVIS, BR BLAUFOX, MD OBERMAN, A WASSERTHEILSMOLLER, S ZIMBALDI, N CUTLER, JA KIRCHNER, K LANGFORD, HG AF DAVIS, BR BLAUFOX, MD OBERMAN, A WASSERTHEILSMOLLER, S ZIMBALDI, N CUTLER, JA KIRCHNER, K LANGFORD, HG TI REDUCTION IN LONG-TERM ANTIHYPERTENSIVE MEDICATION REQUIREMENTS - EFFECTS OF WEIGHT-REDUCTION BY DIETARY INTERVENTION IN OVERWEIGHT PERSONS WITH MILD HYPERTENSION SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED TRIAL; DIASTOLIC BLOOD-PRESSURE; FINAL REPORT; THERAPY; YOUNG; RESTRICTION; MANAGEMENT; PROGRAM; TRAITS; SODIUM AB Background: Increasing concern over long-term drug treatment of mild hypertension has stimulated several studies of weight reduction. Phase I of the Trial of Antihypertensive Interventions and Management demonstrated a short-term effect of weight loss on blood pressure control in overweight persons with mild hypertension, who were either taking placebo or taking low-dose monotherapy. Phase II investigates the long-term benefit of weight loss on the ability to maintain blood pressure control. Methods: From 10 148 community-based screenees, 587 persons (5.8%), aged 21 to 65 years, entered a multicenter, randomized drug (double-blind, placebo-controlled) and diet trial. Participants had a diastolic blood pressure between 90 and 1 00 mm Hg and were at 110% to 160% of their ideal weight. They were randomized to a usual diet (n=296) or to a weight loss diet (n=291) and within each diet group to placebo, chlorthalidone, 25 mg/d, or atenolol, 50 mg/d. Treatment failure was defined as using additional antihypertensive medications if diastolic blood pressure rose above 90 mm Hg according to protocol-specified criteria. Results: At baseline, mean diastolic blood pressure was 93 mm Hg systolic blood pressure, 143 mm Hg- weight, 88 kg' percent ideal weight, 137%; age, 48 years; 56% were men; and 33% were black. Mean follow-up was 4.5 years. There was a net loss of 2 to 3 kg with weight loss diet compared with usual diet over most of the follow-up period. The 5-year incidence of treatment failure was 56.7 per 100 participants with usual diet and 49.8 per 100 with weight loss. Long-term weight loss decreased failure of blood pressure control for those receiving placebo or low-dose diuretic or beta-blocker by 23%. The results were similar in direction in each drug group. Conclusions: The Trial of Antihypertensive Interventions and Management demonstrated that weight reduction is an effective long-term therapy for maintaining blood pressure in the normal range when used as monotherapy or in combination with either thiazide diuretics or beta-blockers. Consequently, weight loss should be recommended for the management of obese individuals with mild hypertension. C1 YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT NUCL MED,BRONX,NY 10461. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT EPIDEMIOL SOCIAL MED,BRONX,NY 10461. UNIV ALABAMA,DIV GEN PREVENT MED,BIRMINGHAM,AL 35294. NHLBI,DIV EPIDEMIOL CLIN APPLICAT,BETHESDA,MD 20892. UNIV MISSISSIPPI,MED CTR,DEPT MED,JACKSON,MS 39216. RP DAVIS, BR (reprint author), UNIV TEXAS,SCH PUBL HLTH,COORDINATING CTR CLIN TRIALS,1200 HERMAN PRESSLER ST,HOUSTON,TX 77030, USA. FU NHLBI NIH HHS [HL-40072, HL-24369, HL-30171] NR 45 TC 80 Z9 80 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD AUG 9 PY 1993 VL 153 IS 15 BP 1773 EP 1782 DI 10.1001/archinte.153.15.1773 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA LQ367 UT WOS:A1993LQ36700003 PM 8333814 ER PT J AU SUZUKI, M ITOH, T OSADA, H RUBIN, JS AARONSON, SA SUZUKI, T KOGA, N SAITO, T MITSUI, Y AF SUZUKI, M ITOH, T OSADA, H RUBIN, JS AARONSON, SA SUZUKI, T KOGA, N SAITO, T MITSUI, Y TI SPLEEN-DERIVED GROWTH-FACTOR, SDGF-3, IS IDENTIFIED AS KERATINOCYTE GROWTH-FACTOR (KGF) SO FEBS LETTERS LA English DT Article DE SDGF-3; KERATINOCYTE GROWTH FACTOR; BOVINE SPLEEN; PRIMARY CULTURED HEPATOCYTE; HEPARIN BINDING ID LIVER-REGENERATION; DNA-SYNTHESIS; PURIFICATION; HEPATOCYTES; REGULATOR; AUTOCRINE; CULTURES AB A heparin-binding mitogen rat for rat hepatocytes was partially purified from bovine spleen by a combination of heparin-affinity, cation-exchange and gel-filtration chromatography. Besides stimulating rat hepatocytes, this factor, which was designated spleen-derived growth factor-3 (SDGF-3), exhibited mitogenic activity for mouse epidermal keratinocytes but not mouse fibroblasts. Its apparent epithelial specificity and heparin-binding properties corresponded to those of keratinocyte growth factor (KGF). These findings, together with the fact that the mitogenic activity of SDGF-3 was abolished by a neutralizing monoclonal antibody specific for KGF, identify this bovine spleen-derived hepatocyte mitogen as KGF. C1 NATL INST BIOSCI & HUMAN TECHNOL,CELL BIOL LAB,HIGASHI 1-1 TSUKUBA SCI CITY,IBARAKI 305,JAPAN. MAYEKAWA MFG CO LTD,ADV TECHNOL LAB,IBARAKI 30201,JAPAN. RIKEN,INST PHYS & CHEM RES,ANTIBIOT LAB,WAKO,SAITAMA 30501,JAPAN. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. GIFU UNIV,FAC AGR,DEPT BIOTECHNOL,GIFU 50111,JAPAN. GOVT IND RES INST,DIV MAT CHEM,NAGOYA,AICHI 462,JAPAN. RI Osada, Hiroyuki/N-4305-2014 NR 20 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD AUG 9 PY 1993 VL 328 IS 1-2 BP 17 EP 20 DI 10.1016/0014-5793(93)80956-U PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA LR081 UT WOS:A1993LR08100005 PM 8344423 ER PT J AU LAM, WC MAKI, AH CASASFINET, JR ERICKSON, JW SOWDER, RC HENDERSON, LE AF LAM, WC MAKI, AH CASASFINET, JR ERICKSON, JW SOWDER, RC HENDERSON, LE TI EVIDENCE FOR STACKING INTERACTIONS BETWEEN 5-MERCURATED POLYURIDYLIC ACID AND HIV-1 P7 NUCLEOCAPSID PROTEIN OBTAINED BY PHOSPHORESCENCE AND OPTICALLY DETECTED MAGNETIC-RESONANCE (ODMR) SO FEBS LETTERS LA English DT Article DE EXTERNAL HEAVY ATOM EFFECT; TRYPTOPHAN PHOSPHORESCENCE; ODMR SPECTROSCOPY; ZINC FINGER RNA INTERACTION ID IMMUNODEFICIENCY-VIRUS TYPE-1; BINDING-PROTEINS; TRIPLET-STATE; TRYPTOPHAN; RETROVIRUSES; METHYLMERCURY; SEQUENCES; COMPLEXES; SUBLEVELS; ZINC AB The photoexcited triplet state of Trp-37 in the C-terminal zinc finger of the HIV-1 p7 nucleocapsid protein was used as a probe of p7 interactions with the heavy atom-derivatized RNA homopolymer, poly-5-mercuriuridylic acid (5-HgU). Binding of p7 to 5-HgU (Hg blocked with 2-mercaptoethanol) produces an external heavy atom effect (HAE) on Trp-37 characterized by fluorescence quenching, reduction of the phosphorescence lifetime by three orders of magnitude, and the appearance of the D + E phosphorescence-detected ODMR signal, absent in unperturbed Trp, but induced by a HAE. The details of the HAE are consistent with out-of-plane van der Waals contact of Hg with the indole chromophore of Trp-37. Steric requirements suggest further that the Trp-RNA contact occurs via an aromatic stacking interaction. C1 UNIV CALIF DAVIS,DEPT CHEM,DAVIS,CA 95616. NCI,PRI DYNCORP,FCRDC,FREDERICK,MD 21702. FU NIEHS NIH HHS [ES-02662] NR 29 TC 10 Z9 10 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD AUG 9 PY 1993 VL 328 IS 1-2 BP 45 EP 48 DI 10.1016/0014-5793(93)80962-T PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA LR081 UT WOS:A1993LR08100011 PM 8344433 ER PT J AU BENZING, WC IKONOMOVIC, MD BRADY, DR MUFSON, EJ ARMSTRONG, DM AF BENZING, WC IKONOMOVIC, MD BRADY, DR MUFSON, EJ ARMSTRONG, DM TI EVIDENCE THAT TRANSMITTER-CONTAINING DYSTROPHIC NEURITES PRECEDE PAIRED HELICAL FILAMENT AND ALZ-50 FORMATION WITHIN SENILE PLAQUES IN THE AMYGDALA OF NONDEMENTED ELDERLY AND PATIENTS WITH ALZHEIMERS-DISEASE SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE BETA-AMYLOID; CHOLINERGIC; NEUROPEPTIDES; PATHOGENESIS; IMMUNOCYTOCHEMISTRY ID DOWNS-SYNDROME; NEUROFIBRILLARY TANGLES; AMYLOID DEPOSITS; SUBSTANCE-P; NEUROTENSIN IMMUNOREACTIVITY; PROTEIN; BRAINS; DEMENTIA; SYSTEMS; PATHOGENESIS AB Immunocytochemical techniques were employed to examine the temporal ordering whereby amyloid beta-protein (AbetaP) and neuronal elements collectively come together to form senile plaques in Alzheimer's disease (AD). Specifically, we addressed three questions: (1) whether AbetaP deposition precedes or follows neuritic changes; (2) whether paired helical filament (PHF) formation is an early or late event in the genesis of the dystrophic neurites which participate in plaque formation; and (3) whether the density of senile plaques displays any relationship with the prevalence of PHF or Alz-50 containing neurons. To address these questions we studied the amygdala from a group of patients with AD, a group of nondemented age-matched individuals exhibiting a sufficient number of senile plaques to be classified by neuropathological criteria as AD, and a group of age-matched controls without AD pathology. Amyloid-bearing plaques were demonstrated by AbetaP immunolabeling and thioflavine-S staining. Neuritic changes in the form of dystrophic neurites were observed with the aid of antibodies against PHF, Alz-50, as well as antibodies against several neuropeptides (i.e., substance P, somatostatin, and neurotensin) and the acetylcholine biosynthetic enzyme, choline acetyltransferase. By using a graded range of pathologic changes both within and across the patient population to provide us with a means of evaluating plaque deposition from its earliest to most advanced stages of development, we observed in patients and/or regions of the amygdala displaying a mild degree of pathologic change AbetaP deposition in the absence of any neuritic changes. With increasing density of AbetaP, however, we began to observe dystrophic neurites within plaques. In regions of relatively few plaques, the dystrophic neurites were immunolabeled only with antibodies against the various neurotransmitters and they lacked evidence of cytoskeletal pathology (i.e., Alz-50 or PHF). Only as the density of AbetaP increased further within a region, were dystrophic neurites observed that exhibited Alz-50 or PHF. In no instance did we observe a relationship between the density of AbetaP deposition and the density of Alz-50 or PHF-immunoreactive neurons. Collectively, our data suggest that the deposition of AbetaP is an early pathologic event in senile plaque formation. Thereafter, swollen neurites can be seen in the vicinity of AbetaP. This early neuritic response, which can first be visualized by immunolabeling for one or another transmitter substance, is followed by alterations in the cytoskeleton as recognized initially by antibodies to Alz-50 and subsequently by the presence of PHF. (C) 1993 Wiley-Liss, Inc. C1 GEORGETOWN UNIV,GEORGETOWN INST NEUROSCI,FIDIA,WASHINGTON,DC 20007. NIA,NEUROSCI LAB,BETHESDA,MD 20892. RUSH PRESBYTERIAN ST LUKES MED CTR,DEPT NEUROL,CHICAGO,IL 60612. FU NIA NIH HHS [AG10688, AG05344, AG08206] NR 74 TC 46 Z9 46 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD AUG 8 PY 1993 VL 334 IS 2 BP 176 EP 191 DI 10.1002/cne.903340203 PG 16 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA LP819 UT WOS:A1993LP81900002 PM 7690048 ER PT J AU BREIER, A CRANE, AM KENNEDY, C SOKOLOFF, L AF BREIER, A CRANE, AM KENNEDY, C SOKOLOFF, L TI THE EFFECTS OF PHARMACOLOGICAL DOSES OF 2-DEOXY-D-GLUCOSE ON LOCAL CEREBRAL BLOOD-FLOW IN THE AWAKE, UNRESTRAINED RAT SO BRAIN RESEARCH LA English DT Article DE GLUCOSE DEPRIVATION; GLYCOLYTIC BLOCKADE; DEOXYGLUCOSE ID INSULIN-INDUCED HYPOGLYCEMIA; OXIDATIVE-METABOLISM; UNANESTHETIZED RATS; BRAIN; RECOVERY; CORTEX AB Previous studies on the effects of acute insulin-induced hypoglycemia on cerebral blood flow (CBF) have resulted in conflicting results. An alternate approach to the study of glucoprivation is the administration of pharmacologic doses of the glucose analogue, 2-deoxy-D-glucose (2-DG). 2-DG is transported across the blood-brain barrier into brain tissue where it is phosphorylated to 2-deoxy-D-glucose-6-phosphate (2-DG-6-P) but not metabolized further. The 2-DG-6-P accumulates and inhibits the conversion of glucose-6-phosphate to fructose-6-phosphate, thus blocking glycolysis and glucose metabolism. In the present study we have employed the [C-14]iodoantipyrine method to examine the effects of a pharmacologic dose (500 mg/kg) of 2-DG on local cerebral blood flow (ICBF) in 29 regions of the brain in conscious, unrestrained, adult male rats. The 2-DG treatment raised arterial plasma glucose levels from 8 to 17 mM without affecting arterial blood pO2, pCO2, or pH but increased ICBF in most brain regions examined. The largest increases were in the cerebral cortex, basal ganglia, and thalamic nuclei (+ 65 to + 157%). Smaller increases were found in most structures of the limbic system. brainstem, and white matter, and no changes in ICBF were seen in the cerebellar cortex and ventral medial hypothalamus. The results indicate that cerebral glucoprivation produced by pharmacological doses of 2-deoxyglucose is accompanied by substantial increase in blood flow in most regions of the brain. C1 NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. RP BREIER, A (reprint author), UNIV MARYLAND,DEPT PSYCHIAT,MARYLAND PSYCHIAT RES CTR,POB 21247,CATONSVILLE,MD 21228, USA. NR 26 TC 27 Z9 27 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 AUG 6 PY 1993 VL 618 IS 2 BP 277 EP 282 DI 10.1016/0006-8993(93)91276-X PG 6 WC Neurosciences SC Neurosciences & Neurology GA LP979 UT WOS:A1993LP97900013 PM 8374758 ER PT J AU ARAI, R JACOBOWITZ, DM DEURA, S AF ARAI, R JACOBOWITZ, DM DEURA, S TI IMMUNOHISTOCHEMICAL LOCALIZATION OF CALRETININ-CONTAINING, CALBINDIN-D28K-CONTAINING AND PARVALBUMIN-CONTAINING CELLS IN THE HYPOTHALAMIC PARAVENTRICULAR AND SUPRAOPTIC NUCLEI OF THE RAT SO BRAIN RESEARCH LA English DT Note DE CALCIUM-BINDING PROTEIN; CALRETININ; CALBINDIN-D28K; PARVALBUMIN; PARAVENTRICULAR NUCLEUS; SUPRAOPTIC NUCLEUS; RAT ID CALCIUM-BINDING PROTEIN; SPINAL-CORD; HORSERADISH-PEROXIDASE; NONPYRAMIDAL NEURONS; MEDIAN-EMINENCE; BRAIN; THALAMUS; IMMUNOREACTIVITY; PITUITARY; CONNECTIONS AB The localization of three calcium-binding proteins, calretinin, calbindin-D28k and parvalbumin, in the hypothalamic paraventricular and supraoptic nuclei of the rat was immunohistochemically examined on adjacent sections and their distribution patterns were compared. Overlap between the distribution of calretinin-immunoreactive cells and that of calbindin-D28k-immunostained cells was found in the rostrodorsal part of the supraoptic nucleus, and the caudoventral part of this nucleus contained predominantly calbindin-D28k-stained cells. Cells of the medial and lateral magnocellular subdividions of the paraventricular nucleus were almost devoid of the calcium-binding proteins examined. No parvalbumin-immunostained cells were observed in either nucleus. This study provides a further characterization of cell bodies in the hypothalamic paraventricular and supraoptic nuclei. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. RP ARAI, R (reprint author), FUJITA HLTH UNIV,SCH MED,DEPT ANAT,TOYOAKE,AICHI 47011,JAPAN. NR 50 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 6 PY 1993 VL 618 IS 2 BP 323 EP 327 DI 10.1016/0006-8993(93)91284-Y PG 5 WC Neurosciences SC Neurosciences & Neurology GA LP979 UT WOS:A1993LP97900021 PM 8374764 ER PT J AU SHINOMIYA, K MENET, JM FALES, HM ITO, Y AF SHINOMIYA, K MENET, JM FALES, HM ITO, Y TI STUDIES ON A NEW CROSS-AXIS COIL PLANET CENTRIFUGE FOR PERFORMING COUNTERCURRENT CHROMATOGRAPHY .1. DESIGN OF THE APPARATUS, RETENTION OF THE STATIONARY-PHASE, AND EFFICIENCY IN THE SEPARATION OF PROTEINS WITH POLYMER PHASE SYSTEMS SO JOURNAL OF CHROMATOGRAPHY LA English DT Article ID PARTITION EFFICIENCY; ROTARY SEALS AB An improved model of the cross-axis synchronous flow-through coil planet centrifuge has been designed in light of previous studies. The apparatus has a versatile feature in that both analytical and preparative columns can be accommodated in both off-center and central positions. Each has merit in separations. Retention of stationary phase was examined with various two-phase solvent systems used for the separation of biopolymers. Both analytical and preparative columns showed satisfactory retention of the stationary phase under optimum conditions. The apparatus was evaluated in separation of a set of protein samples using a polyethylene glycol-potassium phosphate biphasic system. In both types of columns all proteins were resolved with partition efficiencies of 260 to 670 theoretical plates. Further studies indicated that the relatively low partition efficiency of proteins is mainly attributed to their high molecular mass or molecular heterogeneity within each species rather than due to the high viscosity of the polymer phase system. C1 NHLBI,BIOPHYS CHEM LAB,BLDG 10,ROOM 7N322,BETHESDA,MD 20892. NR 14 TC 50 Z9 50 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR PD AUG 6 PY 1993 VL 644 IS 2 BP 215 EP 229 DI 10.1016/0021-9673(93)80703-B PG 15 WC Chemistry, Analytical SC Chemistry GA LT326 UT WOS:A1993LT32600001 PM 8408404 ER PT J AU MENET, JM ITO, Y AF MENET, JM ITO, Y TI STUDIES ON A NEW CROSS-AXIS COIL PLANET CENTRIFUGE FOR PERFORMING COUNTERCURRENT CHROMATOGRAPHY .2. PATH AND ACCELERATION OF COILS AND COMPARISON WITH TYPE-J COIL PLANET CENTRIFUGE SO JOURNAL OF CHROMATOGRAPHY LA English DT Article ID APPARATUS AB A comprehensive approach is introduced using parametric equations to describe the motion induced by type J and cross-axis type coil planet centrifuges. The plots of a line parallel to the coil axis are given. The centrifugal forces are then analyzed in two ways. Three-dimensional graphs show their geometry and the relative intensity of the lateral component is compared to that of the perpendicular component. This allowed a better understanding of the differences in paths and acceleration fields induced by the two types of counter-current chromatography devices. C1 NHLBI,BIOPHYS CHEM LAB,BLDG 10,ROOM 7N322,BETHESDA,MD 20892. NR 10 TC 9 Z9 9 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR PD AUG 6 PY 1993 VL 644 IS 2 BP 231 EP 238 DI 10.1016/0021-9673(93)80704-C PG 8 WC Chemistry, Analytical SC Chemistry GA LT326 UT WOS:A1993LT32600002 PM 8408405 ER PT J AU MENET, JM SHINOMIYA, K ITO, Y AF MENET, JM SHINOMIYA, K ITO, Y TI STUDIES ON NEW CROSS-AXIS COIL PLANET CENTRIFUGE FOR PERFORMING COUNTERCURRENT CHROMATOGRAPHY .3. SPECULATIONS ON THE HYDRODYNAMIC MECHANISM IN STATIONARY-PHASE RETENTION SO JOURNAL OF CHROMATOGRAPHY LA English DT Article ID XLL AB Retention of the stationary phases of one organic-aqueous solvent system and three aqueous-aqueous polymer solvent systems was investigated on a cross-axis coil planet centrifuge. A graphic statistical treatment of all the data highlighted the prevailing effect of the inward-outward elution mode. A simplified model was proposed and studies on the paths and accelerations of cross-axis devices described in the previous paper provided explanations about the observed hydrodynamic behaviors. C1 NHLBI,BIOPHYS CHEM LAB,BLDG 10,ROOM 7N322,BETHESDA,MD 20892. NR 7 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR PD AUG 6 PY 1993 VL 644 IS 2 BP 239 EP 252 DI 10.1016/0021-9673(93)80705-D PG 14 WC Chemistry, Analytical SC Chemistry GA LT326 UT WOS:A1993LT32600003 PM 8408406 ER PT J AU DECOSTA, BR HE, XS LINDERS, JTM DOMINGUEZ, C GU, ZQ WILLIAMS, W BOWEN, WD AF DECOSTA, BR HE, XS LINDERS, JTM DOMINGUEZ, C GU, ZQ WILLIAMS, W BOWEN, WD TI SYNTHESIS AND EVALUATION OF CONFORMATIONALLY RESTRICTED N-[2-(3,4-DICHLOROPHENYL)ETHYL]-N-METHYL-2-(1-PYRROLIDINYL)ETHYLAMINES AT SIGMA-RECEPTORS .2. PIPERAZINES, BICYCLIC AMINES, BRIDGED BICYCLIC AMINES, AND MISCELLANEOUS COMPOUNDS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID C57BL/6 MOUSE-BRAIN; HIGH-AFFINITY; BINDING-SITES; BIOLOGICAL EVALUATION; LIGANDS; DOPAMINE; ANALOGS; AGENTS; RAT AB As a continuation of our earlier study (J. Med. Chem. 1992, 35, 4334-4343) we conformationally restricted the sigma-receptor ligand 2-(1-pyrrolidinyl)-N-[2-(3,4-dichlorophenyl)ethyl]-N-methylethylamine (1) by incorporating it into a series of homologous piperazines 3-9 and homopiperazines 10 and 11, diazabicyclononanes and decanes, bridgehead bicyclooctanes and nonanes as well as other miscellaneous compounds. Sigma-receptor binding affinities were obtained using [H-3](+)-pentazocine in guinea pig brain membrane sigma1 sites. The studies suggest that the nitrogen lone pair orientation found in the piperazines affords the strongest binding interaction. Other nitrogen lone pair orientations or compounds representing unlikely staggered conformations of 1 [as in 4-[2-(3,4-dichlorophenyl)ethyl] -1,4-diazabicyclo[3.2.2] nonane (16)] show very weak sigma interaction. Comparison of the binding data of different N-substituted homologues of 1 with those of the 1-[2-(3,4-dichlorophenyl)ethyl]-4-alkylpiperazines suggests that the two nitrogen atoms of 1 are working in opposition to one another in terms of their sensitivity to steric bulk. The high binding affinity of the 1,4-diazabicyclo[4.3.0]nonanes 12 suggests that these may approximate the methyl and pyrrolidine ring conformations found in 1 when it is bound to the sigma receptor. Compound 12 exhibited a 4-fold enantioselectivity favoring (+)-12. The synthesis of 6,7-dichloro-2-[[2-(1-pyrrolidinyl)ethyl]amino]tetralin (19) and its desmethyl derivative 20 permitted constraint of the 3,4-dichlorophenyl and N-methyl moieties of 1 into a gauche orientation. The binding data suggests that this conformation in 1 favors strong binding interaction at sigma-receptors. Sigma-receptor K(i)'s ranged from 0.55 nM for 1-[2-(3,4-dichlorophenyl)ethyl]-4-n-butylpiperazine(7) to 654 nM for 16. Overall comparison of the results indicate that 1 is subject to considerable conformational freedom and suggests that the sigma receptor is not subject to rigid stereochemical restraints with 1. These results add to our earlier study where we restrained 1 using simple monocyclic heterocycles. RP DECOSTA, BR (reprint author), NIDDKD,MED CHEM LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 39 TC 49 Z9 49 U1 0 U2 4 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 AUG 6 PY 1993 VL 36 IS 16 BP 2311 EP 2320 DI 10.1021/jm00068a007 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA LT442 UT WOS:A1993LT44200007 PM 8360875 ER PT J AU SHIRINSKY, VP VOROTNIKOV, AV BIRUKOV, KG NANAEV, AK COLLINGE, M LUKAS, TJ SELLERS, JR WATTERSON, DM AF SHIRINSKY, VP VOROTNIKOV, AV BIRUKOV, KG NANAEV, AK COLLINGE, M LUKAS, TJ SELLERS, JR WATTERSON, DM TI A KINASE-RELATED PROTEIN STABILIZES UNPHOSPHORYLATED SMOOTH-MUSCLE MYOSIN MINIFILAMENTS IN THE PRESENCE OF ATP SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LIGHT-CHAIN KINASE; HEAVY-MEROMYOSIN; CHICKEN GIZZARD; SKELETAL-MUSCLE; CALMODULIN; BINDING; PHOSPHORYLATION; FILAMENTS; ACTIN; PURIFICATION AB An apparent paradox in smooth muscle biology is the ability of unphosphorylated myosin to maintain a filamentous structure in the presence of ATP in vivo, whereas unphosphorylated myosin filaments are depolymerized in vitro in the presence of ATP. This suggests that additional uncharacterized factors are required for the stabilization of myosin filaments in the presence of ATP. We report here that an abundant smooth muscle protein forms sedimentable complexes with unphosphorylated smooth muscle myosin, partially reverses the depolymerizing effect of ATP on unphosphorylated myosin, and promotes the assembly of minifilaments as revealed by electron microscopy. This protein is called kinase-related protein (KRP) because it is derived from a gene within the gene for myosin light chain kinase (MLCK) and has an amino acid sequence identical to the carboxyl-terminal domain of MLCK. Consistent with the results with purified KRP, deletion of the KRP domain within MLCK results in a diminished ability of MLCK to interact with unphosphorylated myosin. KRP binds to the heavy meromyosin fragment of myosin but not to myosin rod or fragments lacking the hinge region and light chains. Altogether, these results suggest that KRP may play a critical role in stabilizing unphosphorylated myosin filaments and that the KRP domain of MLCK may be important for subcellular targeting to filaments. C1 NHLBI,MOLEC CARDIOL LAB,BETHESDA,MD 20892. RUSSIAN ACAD MED SCI,CARDIOL RES CTR,MOLEC ENDOCRINOL LAB,MOSCOW 121552,RUSSIA. RP SHIRINSKY, VP (reprint author), VANDERBILT UNIV,DEPT PHARMACOL,NASHVILLE,TN 37232, USA. RI Vorotnikov, Alexander/A-8392-2014; OI Vorotnikov, Alexander/0000-0002-1460-971X; Watterson, Daniel/0000-0001-7605-5866 FU NHLBI NIH HHS [HL47070]; NIGMS NIH HHS [GM30861] NR 36 TC 106 Z9 108 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 AUG 5 PY 1993 VL 268 IS 22 BP 16578 EP 16583 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LQ336 UT WOS:A1993LQ33600072 PM 8344938 ER PT J AU OOI, GT BROWN, DR SUH, DS TSENG, LYH RECHLER, MM AF OOI, GT BROWN, DR SUH, DS TSENG, LYH RECHLER, MM TI CYCLOHEXIMIDE STABILIZES INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-1 (IGFBP-1) MESSENGER-RNA AND INHIBITS IGFBP-1 TRANSCRIPTION IN H4-II-E RAT HEPATOMA-CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID 3' UNTRANSLATED REGION; PHOSPHOENOLPYRUVATE CARBOXYKINASE GTP; GENE-EXPRESSION; C-FOS; MULTIHORMONAL REGULATION; TRANSFERRIN RECEPTOR; REGENERATING LIVER; DOMINANT ROLE; BETA-TUBULIN; 3T3 CELLS AB The insulin-like growth factor-binding proteins (IGFBPs) are a family of six proteins that modulate the biological activity of IGF-I and IGF-II and determine their bioavailability to tissues. One of the IGFBPs, IGFBP-1, is distinctive in the dynamic response of its levels in human plasma to metabolic changes. Parallel changes occur in IGFBP-1 mRNA and IGFBP-1 transcription in rat liver. Using the well differentiated H4-II-E rat hepatoma cell line as a model system, we demonstrated previously that IGFBP-1 transcription is positively regulated by dexamethasone and negatively regulated by insulin. We now examine the effect of the protein synthesis inhibitor, cycloheximide, on the hormonal regulation of IGFBP-1 gene expression. Preincubation of H4-II-E cells with 10.7 muM cycloheximide for 1.5 h did not prevent the induction of IGFBP-1 mRNA and IGFBP-1 transcription (determined in nuclear run-on assays) by dexamethasone. By contrast, cycloheximide treatment abolished the decrease in IGFBP-1 mRNA induced by insulin. Insulin rapidly decreased IGFBP-1 transcription in the absence of cycloheximide (>50% inhibition in 20 min) and caused a similar decrease in cells pretreated with cycloheximide. Cycloheximide alone also decreased IGFBP-1 transcription. Similar results were observed with a second protein synthesis inhibitor, anisomycin, which also prevented the insulin-induced decrease in IGFBP-1 mRNA without abolishing the insulin-induced inhibition of IGFBP-1 transcription. These results suggest that although insulin decreases IGFBP-1 gene transcription in the presence of protein synthesis inhibitors, IGFBP-1 mRNA levels are maintained because of stabilization of the mRNA. Stabilization was demonstrated directly in actinomycin D-treated cells, where the t1/2 of IGFBP-1 mRNA increased from approximately 2 to approximately 20 h in the presence of cycloheximide; insulin did not affect IGFBP-1 mRNA turnover. Thus, cycloheximide-sensitive labile proteins contribute to the maintenance of basal IGFBP-1 promoter activity and the rapid turnover of IGFBP-1 mRNA, which determine the dynamic regulation of IGFBP-1 gene expression. RP OOI, GT (reprint author), NIDDKD,MOLEC & CELLULAR ENDOCRINOL BRANCH,GROWTH & DEV SECT,BLDG 10,RM 8D14,BETHESDA,MD 20892, USA. NR 78 TC 35 Z9 35 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 AUG 5 PY 1993 VL 268 IS 22 BP 16664 EP 16672 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LQ336 UT WOS:A1993LQ33600083 PM 7688368 ER PT J AU CHAE, HZ KIM, IH KIM, K RHEE, SG AF CHAE, HZ KIM, IH KIM, K RHEE, SG TI CLONING, SEQUENCING, AND MUTATION OF THIOL-SPECIFIC ANTIOXIDANT GENE OF SACCHAROMYCES-CEREVISIAE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MANGANESE-SUPEROXIDE-DISMUTASE; GLUTATHIONE-PEROXIDASE; HYDROGEN-PEROXIDE; NUCLEOTIDE-SEQUENCE; FREE-RADICALS; NUCLEAR GENE; OXIDATION; YEAST; PROTEIN; INACTIVATION AB We have previously shown that the yeast Saccharomyces cerevisiae contains an antioxidant enzyme that can provide protection against a thiol-containing oxidation system but not against an oxidation system without thiol. This 25-kDa enzyme was thus named thiol-specific antioxidant (TSA). We have now isolated and sequenced a yeast genomic DNA fragment that encodes TSA. Comparison of the predicted amino acid sequence of TSA with those of conventional antioxidant enzymes, including catalases, peroxidases, and superoxide dismutases, revealed no sequence homology. The 195-amino acid TSA sequence contains 2 cysteine residues. Southern blot analysis of petite yeast DNA, studies with protein synthesis inhibitors, and protein immunoblot analyses of cytosolic and mitochondrial proteins suggest that TSA is a cytosolic protein encoded by nuclear DNA (chromosome XIII). The yeast TSA gene was selectively disrupted by homologous recombination. The haploid tsa mutant was viable under air, suggesting that TSA is not essential for cell viability. The growth rates of the tsa mutant and wild-type strains were identical under anaerobic conditions. However, under aerobic conditions, especially in the presence of methyl viologen or a peroxide (t-butyl hydroperoxide or H2O2), the growth rate of the mutant was significantly less than that of wild-type cells. This result suggests that TSA is a physiologically important antioxidant. C1 NHLBI,BIOCHEM LAB,BLDG 3,RM 122,BETHESDA,MD 20892. NR 49 TC 260 Z9 270 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 AUG 5 PY 1993 VL 268 IS 22 BP 16815 EP 16821 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LQ336 UT WOS:A1993LQ33600103 PM 8344960 ER PT J AU JOHNSON, JT FERRETTI, GA NETHERY, WJ VALDEZ, IH FOX, PC NG, D MUSCOPLAT, CC GALLAGHER, SC AF JOHNSON, JT FERRETTI, GA NETHERY, WJ VALDEZ, IH FOX, PC NG, D MUSCOPLAT, CC GALLAGHER, SC TI ORAL PILOCARPINE FOR POSTIRRADIATION XEROSTOMIA IN PATIENTS WITH HEAD AND NECK-CANCER SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CONTAINING ARTIFICIAL SALIVA; BLIND CROSSOVER TRIAL; SUBSTITUTES; MUCINS AB Background and Methods. We evaluated pilocarpine hydrochloride for the treatment of radiation-induced xerostomia, a common complication of irradiation of the head and neck. A prospective, randomized, double-blind, placebo-controlled trial was undertaken to test the safety and efficacy of pilocarpine, particularly in reversing the decrease in the production of saliva and other manifestations of xerostomia. Patients received either placebo or pilocarpine (5 mg or 10 mg orally three times a day) for 12 weeks and were evaluated at base line and every 4 weeks. Results. We studied 207 patients who had each received greater-than-or-equal-to 4000 cGy of radiation to the head and neck. In the patients receiving the 5-mg dose of pilocarpine, oral dryness improved in 44 percent, as compared with 25 percent of the patients receiving placebo (P = 0.027). There was overall improvement in 54 percent of the 5-mg group as compared with 25 percent of the placebo group (P = 0.003), and 31 percent of the 5-mg group had improved comfort of the mouth and tongue, as compared with 10 percent of the placebo group (P = 0.002). Speaking ability improved in 33 percent of the 5-mg group as compared with 18 percent of the placebo group (P = 0.037). Saliva production was improved, but it did not correlate with symptomatic relief. There were comparable improvements in the group receiving the 10-mg dose. The primary adverse effect was sweating, in addition to other minor cholinergic effects. Six and 29 percent of the patients in the 5-mg and 10-mg groups, respectively, withdrew from the study because of adverse effects. There were no serious adverse effects related to pilocarpine. Conclusions. Pilocarpine improved saliva production and relieved symptoms of xerostomia after irradiation for cancer of the head and neck, with minor side effects that were predominantly limited to sweating. C1 UNIV KENTUCKY,LEXINGTON,KY 40506. LOMA LINDA UNIV,LOMA LINDA,CA 92350. NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. PHARMACO DYNAM RES,AUSTIN,TX. MGI PHARMA,MINNEAPOLIS,MN. RP JOHNSON, JT (reprint author), UNIV PITTSBURGH,SCH MED,DEPT OTOLARYNGOL,203 LOTHROP ST,SUITE 500,PITTSBURGH,PA 15261, USA. NR 23 TC 286 Z9 293 U1 0 U2 10 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 5 PY 1993 VL 329 IS 6 BP 390 EP 395 DI 10.1056/NEJM199308053290603 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA LQ339 UT WOS:A1993LQ33900003 PM 8326972 ER PT J AU DUCHATEAU, P RADER, D DUVERGER, N THERET, N DEGEITERE, C BREWER, HB FRUCHART, JC CASTRO, GR AF DUCHATEAU, P RADER, D DUVERGER, N THERET, N DEGEITERE, C BREWER, HB FRUCHART, JC CASTRO, GR TI TANGIER DISEASE - ISOLATION AND CHARACTERIZATION OF LPA-I, LPA-II, LPA-I-A-II AND LPA-IV PARTICLES FROM PLASMA SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE HIGH DENSITY LIPOPROTEIN; TANGIER DISEASE; PLASMA LIPOPROTEIN; CHOLESTEROL TRANSPORT; APOLIPOPROTEIN ID HIGH-DENSITY-LIPOPROTEIN; CORONARY-ARTERY DISEASE; APOLIPOPROTEIN-C-III; CHOLESTEROL EFFLUX; ADIPOSE-CELLS; INVIVO METABOLISM; HEART-DISEASE; DEFICIENCY; QUANTIFICATION; MUTATION AB Tangier disease (TD) is characterized by extremely low plasma levels of HDL, apoA-I and apoA-II due to very rapid catabolism. However, the risk of premature coronary heart disease (CHD) is not markedly increased in TD. In order to gain insight into reverse cholesterol transport in TD, we isolated LpA-I, LpA-I:A-II, LpA-II and LpA-IV particles from fasting plasma of 5 TD patients. LpA-I composition was similar to control LpA-I, but TD LpA-I had more LCAT and CETP activity (respectively, 0.35 +/- 0.14 and 0.14 +/- 0.04 mumol of cholesterol esterified/h/mug of protein, and 7 +/- 2.5 and 1.4 +/- 0.3 mumol of cholesteryl ester transferred/h/mug of protein). In contrast, TD LpA-I:A-II had abnormal composition, with a low molar ratio of apoA-I to apoA-II (0.2-1.33). In addition, LpA-I:A-II in TD contained a substantial amount of apoA-IV compared with control, making this particle an LpA-I:A-II:A-IV complex. LpA-I:A-II from normal plasma do not promote cholesterol efflux from adipocytes cells, whereas TD LpA-I:A-II:A-IV complexes promoted cholesterol efflux from these cells. Moreover LpA-I:A-II:A-IV complexes have more LCAT and CETP activity than control (respectively 1.2 +/- 0.16 and 0.05 +/- 0.01 mumol of cholesterol esterified/h/mug of protein and, 41 +/- 3.7 and 1 +/- 0.4 mumol of cholesteryl ester transferred/h/mug of protein). The LpA-II particle in TD represented in fact an LpA-II:A-IV complex (75% mol apoA-II and 22% mol apoA-IV). This particle did not promote cholesterol efflux, but LCAT and CETP activity were present. LpA-IV particles had the capacity to promote cholesterol efflux and had both LCAT and CETP activity. LpA-IV may contribute to maintain the reverse cholesterol transport in TD. Our results indicate the potential importance of apoA-IV in maintaining reverse cholesterol transport in TD. In spite of the low steady state HDL-cholesterol levels in TD, LpA-I, LpA-I:A-II:A-IV complex and LpA-IV appear to be active in reverse cholesterol transport and may help to prevent premature CHD in TD. C1 INST PASTEUR,INSERM,U325,1 RUE PROFF CALMETTE,BP 245,F-59019 LILLE,FRANCE. NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. RI Theret, Nathalie/I-2871-2015 NR 37 TC 15 Z9 15 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 AUG 4 PY 1993 VL 1182 IS 1 BP 30 EP 36 DI 10.1016/0925-4439(93)90149-U PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LR041 UT WOS:A1993LR04100004 PM 8347683 ER PT J AU TOPOROWICZ, A GERSTEN, DM HEARING, VJ BROWN, WE VLOCK, DR AF TOPOROWICZ, A GERSTEN, DM HEARING, VJ BROWN, WE VLOCK, DR TI CROSS-REACTIVITY BETWEEN MURINE MELANOMA ANTIGEN-B700 AND A HUMAN MELANOMA-ASSOCIATED ANTIGEN (M-66) RECOGNIZED BY AUTOLOGOUS ANTIBODY EVIDENCE SUGGESTING SHARED EPITOPES SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE MELANOMA; TUMOR-ASSOCIATED ANTIGEN; IMMUNOLOGY; SEROLOGY ID B700 AB We have previously reported the purification and partial characterization of a human melanoma-associated antigen (M-66) recognized by autologous antibody. This antigen was found to be an unusually acidic 66 kDa glycoprotein. In studies of murine melanoma, a 67-kDa albumin-like melanoma-associated antigen (MAA) isolated from B16 melanoma cells has also been reported by our laboratories. Because the murine MAA, B700, has a molecular weight that is nearly the same as M-66, we sought to determine what similarities and differences existed between these two antigens. Human sera S150, which is known to recognize M-66, was found to bind to murine melanoma cell line B16. The addition of purified M-66 inhibited binding of S150 to B16 cells. Binding by S150 was not noted against murine melanoma cell line S91, which is known not to express cell surface B700. Conversely, reactivity of S150 against Y-Mel 84:420, known to express M-66, could be inhibited by preincubation with B16 cells. Four monoclonal antibodies known to recognize B700 were evaluated for-binding against murine B16 and human melanoma cell line Y-Mel 84:420. Binding was noted against both B16 and Y-Mel 84:420 which could be inhibited by the addition of M-66. Binding of S150 was also noted against purified B700 as tested by ELISA. While a comparison of the amino acid composition of the two antigens revealed similarities, M-66 contained 2.8 times as much serine and 0.4 times as much proline as B700. B700 has been reported to be related to serum albumin, which is not the case for M-66. Finally, M-66 is much more acidic than B700 (pI 2-3 vs 4). We conclude that B700 and M-66 share common epitopes, demonstrating that portions of these tumor-associated antigens are preserved across species. C1 GEORGETOWN UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20007. NCI,CELL BIOL LAB,BETHESDA,MD 20892. UNIV PITTSBURGH,SCH MED,PITTSBURGH CANC INST,DIV MED ONCOL,PITTSBURGH,PA 15261. VET ADM MED CTR,PITTSBURGH,PA. CARNEGIE MELLON UNIV,DEPT BIOL SCI,PITTSBURGH,PA 15213. FU NCI NIH HHS [R01 CA-42922] NR 18 TC 4 Z9 4 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 AUG 4 PY 1993 VL 1182 IS 1 BP 51 EP 56 DI 10.1016/0925-4439(93)90152-Q PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LR041 UT WOS:A1993LR04100007 PM 7688577 ER PT J AU KAPIKIAN, AZ AF KAPIKIAN, AZ TI ORAL REHYDRATION THERAPY FOR VIRAL GASTROENTERITIS - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID ACUTE DIARRHEA; CHILDREN RP KAPIKIAN, AZ (reprint author), NIH,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 AUG 4 PY 1993 VL 270 IS 5 BP 579 EP 579 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LP436 UT WOS:A1993LP43600017 ER PT J AU WANG, RS NAKAJIMA, T PARK, SS GELBOIN, HV MURAYAMA, N AF WANG, RS NAKAJIMA, T PARK, SS GELBOIN, HV MURAYAMA, N TI MONOCLONAL ANTIBODY-DIRECTED ASSESSMENT OF TOLUENE INDUCTION OF RAT HEPATIC CYTOCHROME-P450 ISOZYMES SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID LIVER MICROSOMAL CYTOCHROME-P-450; METABOLIZING-ENZYMES; INHALATION EXPOSURE; 3 FORMS; ETHANOL; TRICHLOROETHYLENE; 3-METHYLCHOLANTHRENE; PURIFICATION; SEPARATION; BENZENE AB Cytochrome P450 isozymes induced in rat liver by a range of concentrations of toluene were studied with monoclonal antibodies (MAbs) to specific P450 isozymes and by enzyme assays. Nitrosodimethylamine demethylase activity was significantly increased in microsomes from rats exposed to more than 1000 ppm of toluene, an increase that was dose-dependent. Anti-CYP2E1 significantly inhibited the metabolism of toluene to benzyl alcohol (BA) by about 50%, in microsomes from 1000 to 4000 ppm toluene-exposed rats, at low substrate concentration (0.2 mM). With anti-CYP2B1/2, the rate of BA formation was decreased by 15-17% in microsomes from rats of 2000 and 4000 ppm toluene exposures at high substrate concentration (5.0 mM). On the other hand, anti-CYP2C11/6 inhibited the rate of formation of BA in all of the microsomes, but the extent of inhibition was progressively decreased from 55% in control to 33% in 4000 ppm exposure. Immunoblot analysis with anti-CYP2E1 and anti-CYP2B1/2 revealed stronger immunoreactive bands in microsomes from rats exposed to more than 1000 and 2000 ppm of toluene, respectively. Stronger bands were also observed in microsomes from rats of 2000-4000 ppm toluene exposures with anti-CYP3A1/2, but no immunoreactivity appeared with anti-CYP1A1/2. These results suggest that toluene induces CYP2E1, CYP2B1/2 and CYP3A1/2, but reduces CYP2C11/6, and has no effect on CYP1A1/2. C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RP WANG, RS (reprint author), SHINSHU UNIV,SCH MED,DEPT HYG,MATSUMOTO,NAGANO 390,JAPAN. NR 33 TC 22 Z9 22 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD AUG 3 PY 1993 VL 46 IS 3 BP 413 EP 419 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LR469 UT WOS:A1993LR46900010 PM 8347164 ER PT J AU COLLIER, E CARPENTIER, JL BEITZ, L CARO, LHP TAYLOR, SI GORDEN, P AF COLLIER, E CARPENTIER, JL BEITZ, L CARO, LHP TAYLOR, SI GORDEN, P TI SPECIFIC GLYCOSYLATION SITE MUTATIONS OF THE INSULIN-RECEPTOR ALPHA-SUBUNIT IMPAIR INTRACELLULAR-TRANSPORT SO BIOCHEMISTRY LA English DT Article ID N-LINKED OLIGOSACCHARIDE; VIRUS-G-PROTEIN; ENDOPLASMIC-RETICULUM; 3T3-L1 ADIPOCYTES; CELL-SURFACE; BIOSYNTHESIS; MUTAGENESIS; EXPRESSION; CARBOHYDRATE; ASSOCIATION AB The insulin receptor is a transmembrane protein found on multiple cell types. This receptor is synthesized as a 190-kDa proreceptor which is cleaved to produce mature alpha and beta subunits. The proreceptor contains 18 potential sites for N-linked glycosylation: 14 on the alpha subunit and 4 on the beta subunit. The codons for asparagine in the first four sites at the amino terminus of the alpha subunit were mutated to code for glutamine. This mutant receptor cDNA was stably transfected into NIH 3T3 cells. The insulin receptor produced in these cells remained in the proreceptor form; no mature alpha and beta subunits were produced. The proreceptor was slightly smaller on SDS-PAGE gels than the wild-type proreceptor and contained four less oligosaccharide chains by tryptic peptide mapping. The carbohydrate chains on the mutant proreceptor remained endoglycosidase H sensitive. However, in the presence of brefeldin A, these oligosaccharide chains could be processed to endoglycosidase H resistant chains. By immunofluorescence, the mutant proreceptor was shown to be localized to the endoplasmic reticulum. No insulin receptors could be found on the cell-surface either with cell surface labeling with biotin or with I-125-insulin binding. Thus, glycosylation of the first four N-linked glycosylation sites of the insulin receptor is necessary for the proper processing and intracellular transport of the receptor. This is in contrast to glycosylation at the four sites on the beta subunit which appear not to be important for processing but necessary for signal transduction. Therefore, N-linked glycosylation of the insulin receptor at specific sites has multiple distinctive roles. C1 UNIV GENEVA,DEPT MORPHOL,CH-1211 GENEVA 4,SWITZERLAND. RP COLLIER, E (reprint author), NIDDKD,DIABET BRANCH,SOLAR BLDG,ROOM 4A-20,BETHESDA,MD 20892, USA. NR 36 TC 48 Z9 48 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 AUG 3 PY 1993 VL 32 IS 30 BP 7818 EP 7823 DI 10.1021/bi00081a029 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LV435 UT WOS:A1993LV43500029 PM 8347587 ER PT J AU HULIHANGIBLIN, BA PARK, YD GOLDMAN, D AULAKH, CS AF HULIHANGIBLIN, BA PARK, YD GOLDMAN, D AULAKH, CS TI ANALYSIS OF THE 5-HT(1C) RECEPTOR AND THE SEROTONIN UPTAKE SITE IN FAWN-HOODED RAT-BRAIN SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE [H-3]MESULERGINE; [H-3]PAROXETINE; 5-HT(1C) RECEPTOR; 5-HT (5-HYDROXYTRYPTAMINE, SEROTONIN); 5-HT UPTAKE SITE; BRAIN (RAT) ID H-3 PAROXETINE BINDING; PREFERENCE; 5-HT1C; MCPP AB Both the 5-HT1C receptor and the 5-HT uptake binding sites were measured in Fawn-Hooded, Sprague-Dawley and Wistar rats. Five brain regions were examined: frontal cortex, hippocampus, striatum, hypothalamus, and brainstem. We found significant differences in the B(max) and K(d) values in various brain regions comparing Fawn-Hooded rats, with Sprague-Dawley and Wistar animals. The regional differences in receptor number and affinity in both the 5-HT1C receptor and the 5-HT uptake site in the Fawn-Hooded strain, relative to Wistar and Sprague-Dawley animals, provide support for the use of the Fawn-Hooded rat in serotonin dysfunction studies. C1 NIAAA,NEUROGENET LAB,BETHESDA,MD 20892. NIAAA,CLIN SCI LAB,BETHESDA,MD 20892. RP HULIHANGIBLIN, BA (reprint author), NIAAA,CLIN STUDIES LAB,NEUROCHEM & NEUROENDOCRINOL SECT,CTR CLIN,ROOM 3C-216,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 16 TC 22 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD AUG 3 PY 1993 VL 239 IS 1-3 BP 99 EP 102 DI 10.1016/0014-2999(93)90981-M PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LR547 UT WOS:A1993LR54700014 PM 8223919 ER PT J AU SALONPAA, P HAKKOLA, J PASANEN, M PELKONEN, O VAHAKANGAS, K BATTULA, N NOUSO, K RAUNIO, H AF SALONPAA, P HAKKOLA, J PASANEN, M PELKONEN, O VAHAKANGAS, K BATTULA, N NOUSO, K RAUNIO, H TI RETROVIRUS-MEDIATED STABLE EXPRESSION OF HUMAN CYP2A6 IN MAMMALIAN-CELLS SO EUROPEAN JOURNAL OF PHARMACOLOGY-ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY SECTION LA English DT Article DE CYTOCHROME-P4502A6 (HUMAN); HETEROLOGOUS EXPRESSION; CYP2A6 RECOMBINANT EXPRESSION VECTOR; NIH 3T3 CELLS ID HUMAN-LIVER-MICROSOMES; COUMARIN 7-HYDROXYLASE ACTIVITY; METABOLIC-ACTIVATION; CHEMICAL CARCINOGENESIS; HUMAN CYTOCHROME-P450S; INSERTION SIGNAL; MOUSE; AFLATOXIN-B1; ADDUCTS; ENZYME AB To study the pharmacological and toxicological significance of the human cytochrome P450 isoform CYP2A6, we expressed it in mammalian cells by retrovirus-mediated gene transfer. The LXSN vector and PA317 packaging cells were used to create amphotropic recombinant retroviruses containing CYPZA6 cDNA. NIH 3T3 and HeLa cells were infected with these retroviruses and cell clones expressing CYP2A6 were selected. The integration of the CYP2A6 construct was verified by PCR analysis and northern blot analysis showed that a 5 kb mRNA containing the CYP2A6 was present in the cells. The integrated cDNA directed the expression of catalytically active CYP2A6 enzyme which has remained stable over numerous cell passages. No oxidation of several other P450 substrates was detected. The promutagen aflatoxin B1 was metabolized to intermediates binding to the host cell genomic DNA by the 3T3 2A6 cells. These cell lines are thus well suited for the study of the catalytic profile and the biological consequences of promutagen activation by the human CYP2A6 isoform. C1 UNIV OULU,DEPT PHARMACOL & TOXICOL,SF-90220 OULU,FINLAND. UNIV KUOPIO,DEPT PHARMACOL & TOXICOL,SF-70211 KUOPIO,FINLAND. NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. US FDA,KENSINGTON,MD 20895. NR 35 TC 30 Z9 30 U1 0 U2 0 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 AUG 2 PY 1993 VL 248 IS 2 BP 95 EP 102 DI 10.1016/0926-6917(93)90030-T PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA LU126 UT WOS:A1993LU12600001 PM 8223969 ER PT J AU LINDBERG, DAB AF LINDBERG, DAB TI INFORMATION - AN INTERCONNECTED WORLD SO ACADEMIC MEDICINE LA English DT Editorial Material RP LINDBERG, DAB (reprint author), NATL LIB MED,BETHESDA,MD 20209, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1040-2446 J9 ACAD MED JI Acad. Med. PD AUG PY 1993 VL 68 IS 8 BP 606 EP 607 DI 10.1097/00001888-199308000-00005 PG 2 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA LT199 UT WOS:A1993LT19900006 PM 8394715 ER PT J AU DAVIES, DR CHACKO, S AF DAVIES, DR CHACKO, S TI ANTIBODY STRUCTURE SO ACCOUNTS OF CHEMICAL RESEARCH LA English DT Review ID IMMUNOGLOBULIN FAB FRAGMENT; SITE-DIRECTED MUTAGENESIS; STREPTOCOCCAL PROTEIN-G; 3-DIMENSIONAL STRUCTURE; CRYSTAL-STRUCTURE; ANTIGEN-BINDING; CRYSTALLOGRAPHIC REFINEMENT; MOLECULAR REPLACEMENT; MONOCLONAL-ANTIBODY; 2.8-A RESOLUTION RP DAVIES, DR (reprint author), NIDDKD,MOLEC BIOL LAB,MOLEC STRUCT SECT,BETHESDA,MD 20892, USA. NR 114 TC 82 Z9 82 U1 1 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0001-4842 J9 ACCOUNTS CHEM RES JI Accounts Chem. Res. PD AUG PY 1993 VL 26 IS 8 BP 421 EP 427 DI 10.1021/ar00032a005 PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA LU705 UT WOS:A1993LU70500006 ER PT J AU TARKKA, IM MASSAQUOI, S HALLETT, M AF TARKKA, IM MASSAQUOI, S HALLETT, M TI MOVEMENT-RELATED CORTICAL POTENTIALS IN PATIENTS WITH CEREBELLAR DEGENERATION SO ACTA NEUROLOGICA SCANDINAVICA LA English DT Article DE CEREBELLUM; MOTOR CORTEX; MOVEMENT-RELATED CORTICAL POTENTIALS; BEREITSCHAFTSPOTENTIAL; ELECTROENCEPHALOGRAPHY ID PARKINSONS-DISEASE; VOLUNTARY MOVEMENT; MOTOR POTENTIALS; TOPOGRAPHY; SCALP; CORTEX; ATAXIA AB We studied the topographic distribution of scalp-recorded, averaged movement-related cortical potentials occurring immediately before and after the onset of voluntary movements in six patients with cerebellar degenerative disease. We placed 26 electrodes on the scalp overlying the sensorimotor area and recorded cortical potentials related to abduction of the index finger. The amplitudes and latencies of the potentials were normal in all patients except two, in whom the negative slope (NS') was absent. All patients had an abnormal topographic pattern of potentials compared with normal subjects. The initial slope of motor potential (isMP), which was focal and contralateral in the normal subjects, was diffuse and bilateral in the patients. The topography of the frontal peak of motor potential (fpMP) was more posterior in the patients than in normal subjects. The patterns found in this preliminary study indicate a derangement of sensorimotor cortex activity in voluntary movement as a consequence of cerebellar dysfunction. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BLDG 10,ROOM 5N226,BETHESDA,MD 20892. NR 21 TC 28 Z9 28 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-6314 J9 ACTA NEUROL SCAND JI Acta Neurol. Scand. PD AUG PY 1993 VL 88 IS 2 BP 129 EP 135 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA LU327 UT WOS:A1993LU32700010 PM 8213057 ER PT J AU MUTHEN, BO GRANT, B HASIN, D AF MUTHEN, BO GRANT, B HASIN, D TI THE DIMENSIONALITY OF ALCOHOL-ABUSE AND DEPENDENCE - FACTOR-ANALYSIS OF DSM-III-R AND PROPOSED DSM-IV CRITERIA IN THE 1988 NATIONAL-HEALTH INTERVIEW SURVEY SO ADDICTION LA English DT Article ID UNITED-STATES; USE DISORDERS; VARIABLES AB Decisions on the final version of the DSM-IV alcohol abuse and dependence criteria will be determined largely by the APA's substance abuse field trials, conducted primarily in treated, clinical samples. Among the major objectives of the field trials are to study the boundaries between abuse and dependence, and to identify specific criteria that define the abuse category. The decisions on revisions of the abuse and dependence criteria in DSM-IV should, however, be informed by data from non-treated or general population samples as well. The present study addresses the field trial objectives using recent data from a large general population survey, the 1988 National Health Interview Survey (NHIS88). The paper reports on factor analyses to assess the dimensions underlying the DSM-III-R and DSM-IV dependence and abuse criteria as operationalized in the NHIS88. The focus of the analyses is on whether models with more than one dimension are needed and if so, the correspondence of the dimensions to criteria sets defined in the DSM-III-R and DSM-IV. The analyses show that a two-dimensional model is required. The dimension are interpreted as abuse and dependence, but the sets of criteria that define each of the dimensions show important deviations from the criteria sets used in the DSM definitions. C1 COLUMBIA UNIV,SCH PUBL HLTH,NEW YORK,NY 10027. NEW YORK STATE PSYCHIAT INST & HOSP,NEW YORK,NY 10032. NIAAA,DIV BIOMETRY & EPIDEMIOL,ROCKVILLE,MD 20852. COLUMBIA UNIV COLL PHYS & SURG,NEW YORK,NY 10032. RP MUTHEN, BO (reprint author), UNIV CALIF LOS ANGELES,GRAD SCH EDUC,405 HILGARD AVE,LOS ANGELES,CA 90024, USA. FU NIAAA NIH HHS [NIAAA AA 08651-01] NR 22 TC 134 Z9 135 U1 1 U2 2 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD AUG PY 1993 VL 88 IS 8 BP 1079 EP 1090 DI 10.1111/j.1360-0443.1993.tb02127.x PG 12 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA LQ905 UT WOS:A1993LQ90500006 PM 8401162 ER PT J AU SPROTT, RL AF SPROTT, RL TI MOUSE AND RAT GENOTYPE CHOICES SO AGING-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article; Proceedings Paper CT FRIULI ANIMAL RESEARCH COURSE ON LABORATORY APPROACHES TO AGING CY SEP 08-13, 1991 CL SAN PIETRO AL NATISONE, ITALY SP ASSOC INT RECH & ENSEIGNEMENT NEUROSCI, NIA DE AGING; GENOTYPE; MODELS; MOUSE; RAT AB There are advantages and disadvantages to all animal models for aging research. Investigators need to understand these issues as well as the nature of each relevant model, in order to choose the best model for their research. There is no ''best'' or ''worst'' model for aging research. Five genetically defined rodent models of potential utility in aging research are: 1. Inbred strains and F1 Hybrid mice and rats 2. Single gene mutations and other single locus effects 3. Congenic lines 4. Recombinant Inbred (RI) strains 5. Genetically selected strains and stocks. Animals of each of these types are available for research, but only inbred and F1 hybrid mice and rats are commercially available as aged animals. A general understanding of the need for careful genetic definition and for the best available barrier-breeding facilities has improved the quality of aging research significantly in the last two decades. RP SPROTT, RL (reprint author), NIA,BIOL AGING PROGRAM,GATEWAY BLDG,SUITE 2C231,7201 WISCONSIN AVE,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILANO PA VIA LUIGI ZOJA, 30-20153 MILANO, ITALY SN 0394-9532 J9 AGING-CLIN EXP RES JI Aging-Clin. Exp. Res. PD AUG PY 1993 VL 5 IS 4 BP 249 EP 252 PG 4 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA LY739 UT WOS:A1993LY73900002 PM 8297927 ER PT J AU FOMSGAARD, A JOHNSON, PR LONDON, WT HIRSCH, VM AF FOMSGAARD, A JOHNSON, PR LONDON, WT HIRSCH, VM TI GENETIC-VARIATION OF THE SIV(AGM) TRANSMEMBRANE GLYCOPROTEIN IN NATURALLY AND EXPERIMENTALLY INFECTED PRIMATES SO AIDS LA English DT Article DE SIMIAN IMMUNODEFICIENCY VIRUS; SIV; TRANSMEMBRANE PROTEIN; AFRICAN GREEN MONKEY ID SIMIAN IMMUNODEFICIENCY VIRUS; AFRICAN-GREEN MONKEYS; CYTOPLASMIC DOMAIN; RHESUS-MONKEYS; SEQUENCE; MACAQUES; PROTEIN; SIV; INFECTIVITY; RETROVIRUS AB Objective: An in-frame stop codon prematurely truncating the transmembrane glycoprotein (TMP) is a common feature of many simian immunodeficiency virus, African green monkey strain (SIV(agm)) molecular clones. The purpose of this study was to investigate the native form of the SIV(agm) TMP in a naturally infected African green monkey (AGM) and to study the fate of the stop codon following the passage of SIV(agm) in primates. Design: Polymerase chain reaction was used to clone the entire intracellular portion of the TMP from: (1) peripheral blood mononuclear cells (PBMC) of the naturally infected AGM 155; (2) an isolate of SIV(agm155) in rhesus PBMC and (3) PBMC from pig-tailed macaques and AGM experimentally infected with an SIV(agm) molecular clone encoding a truncated TMP. Results: PBMC of the naturally infected AGM contained a 'swarm' of related virus genotypes that encoded a full-length TMP, whereas tissue-culture passage in rhesus PBMC resulted in a prematurely truncated form of the TMP. This premature stop codon persisted in PBMC of monkeys experimentally infected with an SIV(agm) molecular clone. Both macaques and AGM of same subspecies as AGM 155 (Cercopithecus pygerythrus) and other subspecies (C. aethiops and C. sabaeus) became infected with SIV(agm155). Genetic drift of this region of env, as assessed by calculation of the nucleotide substitution/site/year rate, was similar to that of other retroviruses. Conclusions: The native form of the SIV(agm) TMP is a full-length gp40, similar to the SIV macaque (SIV(mac)) strain and HIV-1. However, passage Of SIV(agm) in tissue culture can result in point mutations that introduce a premature stop codon. This stop codon persists during subsequent in vivo passage Of SIV(agm) in primates. This contrasts with similar studies in macaques infected with SIV(mac), in which reversion of the TMP stop codon was observed. C1 GEORGETOWN UNIV,DEPT MICROBIOL,DIV MOLEC VIROL & IMMUNOL,RETROVIRAL PATHOGENESIS SECT,ROCKVILLE,MD. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. RI Johnson, Philip/A-6892-2009 NR 35 TC 9 Z9 9 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD AUG PY 1993 VL 7 IS 8 BP 1041 EP 1047 DI 10.1097/00002030-199308000-00003 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA LQ772 UT WOS:A1993LQ77200003 PM 8397939 ER PT J AU MARTIN, MP BIGGAR, RJ HAMLINGREEN, G STAAL, S MANN, D AF MARTIN, MP BIGGAR, RJ HAMLINGREEN, G STAAL, S MANN, D TI LARGE GRANULAR LYMPHOCYTOSIS IN A PATIENT INFECTED WITH HTLV-II SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID T-CELL LEUKEMIA; VIRUS TYPE-II; LYMPHOMA VIRUS; RETROVIRUSES; ANTIBODIES; EXPRESSION; DISEASE; ISOLATE; GENE AB HTLV-II has been associated with a variety of lymphoproliferative disorders, including atypical hairy cell leukemia, chronic T cell leukemia, T prolymphocytic leukemia, and large granular lymphocytic leukemia. However, a direct or indirect role for HTLV-II in these disorders is not yet firmly established. We studied a patient diagnosed as having leukemia of the large granular lymphocyte (LGL) type who was HTLV-II seropositive, to determine if the expanded cell population was infected. Two populations of CD3-CD16+ LGL were identified; one was CD8+, the other CD8-. Populations of cells with these surface markers as well as normal CD3+CD4+ and CD3+CD8+ cells were separated by flow cytometric methods, DNA extracted, and gene regions of HTLV-II pol and tax amplified, using the polymerase chain reaction, and probed after Southern blotting. HTLV-II was detected in the CD3-+CD8+ population, and not in the CD3-CD16+ large granular lymphocyte population. This finding indicates that the role of HTLV-II, if any, in LGL proliferation is indirect. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,BLDG 560,ROOM 21-78,FREDERICK,MD 21702. NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20852. NCI,FCRDC,INC DYNCORP,PROGRAM RESOURCES,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. KAISER PERMANENTE MED CTR,LANDOVER,MD 20785. FU PHS HHS [N01-74102] NR 29 TC 42 Z9 42 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 AUG PY 1993 VL 9 IS 8 BP 715 EP 719 DI 10.1089/aid.1993.9.715 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA LX165 UT WOS:A1993LX16500003 PM 8217341 ER PT J AU HYNES, NA ADGERJOHNSON, D DAPOLITO, G HIRSCH, VM AF HYNES, NA ADGERJOHNSON, D DAPOLITO, G HIRSCH, VM TI RAPID SCREENING FOR SIMIAN IMMUNODEFICIENCY VIRUS VARIANTS USING SINGLE-STRAND CONFORMATION POLYMORPHISM OF PCR-AMPLIFIED DNA FRAGMENTS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Note ID DISEASE; TYPE-1; INFECTION; MUTATIONS; STAGE C1 NIAID,INFECT DIS LAB,IMMUNODEFICIENCY VIRUSES SECT,TWINBROOK II FACIL,12441 PARKLAWN DR,ROCKVILLE,MD 20852. NR 8 TC 8 Z9 8 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 1993 VL 9 IS 8 BP 803 EP 806 DI 10.1089/aid.1993.9.803 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA LX165 UT WOS:A1993LX16500015 PM 8217349 ER PT J AU ISAKI, L GORDIS, E AF ISAKI, L GORDIS, E TI ALCOHOL AND IMMUNOLOGY - PROGRESS AND QUESTIONS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR NECROSIS FACTOR; HOMOSEXUAL MEN; OLD MICE; ETHANOL; IMMUNOTOXICITY; INFECTION; HEPATITIS; INVITRO; COHORT RP ISAKI, L (reprint author), NIAAA,5600 FISHERY LANE,ROOM 16C-05,ROCKVILLE,MD 20857, USA. NR 15 TC 9 Z9 9 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 AUG PY 1993 VL 17 IS 4 BP 725 EP 726 DI 10.1111/j.1530-0277.1993.tb00829.x PG 2 WC Substance Abuse SC Substance Abuse GA LT753 UT WOS:A1993LT75300001 PM 8214403 ER PT J AU ZHENG, CF WANG, TTY WEINER, H AF ZHENG, CF WANG, TTY WEINER, H TI CLONING AND EXPRESSION OF THE FULL-LENGTH CDNAS ENCODING HUMAN LIVER CLASS-1 AND CLASS-2 ALDEHYDE DEHYDROGENASE SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ALDEHYDE DEHYDROGENASE; CDNA; CLONING; RECOMBINANTLY EXPRESSED ID ESCHERICHIA-COLI; RAT-LIVER; PURIFICATION; ISOZYMES; PRECURSOR; GENE AB The amino acid sequences of both human class 1 and 2 aldehyde dehydrogenase (ALDH) and the sequences of the genes coding for them are known. Based on this sequence data, we designed primers and isolated the full-length cDNAs encoding both isozymes from a human liver mRNA pool. cDNAs were subcloned in the plasmid pT7-7 and expressed in Escherichia coli with a yield of approximately 3 mg ALDH protein/liter of cell culture, although only one-third of the enzyme was soluble. The soluble recombinantly expressed ALDHs were purified to homogeneity using a hydroxyacetophenone-Sepharose affinity column. The mitochondrial isozyme had a subunit molecular weight of 55 kDa, an isoelectric point of 4.9, and a specific activity of 1.10 units/mg, which were in good agreement with that from the native enzyme. The expressed cytosolic isozyme had the same subunit molecular weight (55 kDa) and pl (5.4) as that reported for the native enzyme and had a specific activity of 0.26 units/mg. The expressed mitochondrial isozyme could be recognized by antibodies raised against rat mitochondrial ALDH, whereas the cytosolic isozyme could be recognized by antibody raised against horse cytosolic ALDH. C1 PURDUE UNIV, DEPT BIOCHEM, W LAFAYETTE, IN 47907 USA. NCI, NUTR & MOLEC REGULAT LAB, FREDERICK, MD 21701 USA. FU NIAAA NIH HHS [AA00038] NR 25 TC 68 Z9 71 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD AUG PY 1993 VL 17 IS 4 BP 828 EP 831 DI 10.1111/j.1530-0277.1993.tb00849.x PG 4 WC Substance Abuse SC Substance Abuse GA LT753 UT WOS:A1993LT75300020 PM 8214422 ER PT J AU ELIN, RJ LINNOILA, M AF ELIN, RJ LINNOILA, M TI LP(A) LEVELS INCREASE AFTER ETHANOL WITHDRAWAL - REPLY SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Letter ID APOLIPOPROTEIN-A-I C1 NIAAA,ROCKVILLE,MD 20852. RP ELIN, RJ (reprint author), NIH,CTR CLIN,DEPT CLIN PATHOL,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD AUG PY 1993 VL 17 IS 4 BP 926 EP 926 DI 10.1111/j.1530-0277.1993.tb00866.x PG 1 WC Substance Abuse SC Substance Abuse GA LT753 UT WOS:A1993LT75300037 ER PT J AU KEMP, CW SHILOACH, J AF KEMP, CW SHILOACH, J TI A SIMPLE COLORIMETRIC ASSAY FOR THE DETERMINATION OF L-GLUTAMINE IN SAMPLES OF TISSUE-CULTURE MEDIUM SO AMERICAN BIOTECHNOLOGY LABORATORY LA English DT Note C1 NIDDK,LCDB,BIOTECHNOL UNIT,BETHESDA,MD. RP KEMP, CW (reprint author), KEMP BIOTECHNOL INC,9141 IND CT,GAITHERSBURG,MD 20877, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU INT SCIENTIFIC COMMUN INC PI SHELTON PA PO BOX 870, 30 CONTROLS DRIVE, SHELTON, CT 06484-0870 SN 0749-3223 J9 AM BIOTECHNOL LAB JI Am. Biotechnol. Lab. PD AUG PY 1993 VL 11 IS 9 BP 12 EP 12 PG 1 WC Biotechnology & Applied Microbiology; Medical Laboratory Technology SC Biotechnology & Applied Microbiology; Medical Laboratory Technology GA LU101 UT WOS:A1993LU10100003 PM 7763941 ER PT J AU KRUMHOLZ, HM LARSON, M LEVY, D AF KRUMHOLZ, HM LARSON, M LEVY, D TI SEX-DIFFERENCES IN CARDIAC ADAPTATION TO ISOLATED SYSTOLIC HYPERTENSION SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LEFT-VENTRICULAR MASS; CORONARY HEART-DISEASE; MORTALITY; HYPERTROPHY; MORBIDITY; GEOMETRY; EXERCISE; GENDER; RAT AB This study examines the association of isolated systolic hypertension with left ventricular (LV) mass and geometry in men and women. The subjects of this study were surviving members of the Framingham Heart Study and the Framingham Offspring Study who attended the index examination (between 1979 and 1983) and were aged greater-than-or-equal-to 50 years, free of clinically apparent cardiovascular disease, not taking antihypertensive medication and without diastolic hypertension (diastolic blood pressure <90 mm Hg), and in whom LV mass could be determined by echocardiography. Examinations routinely included 12-lead resting electrocardiography, measurements of resting blood pressure, anthropometry, blood glucose levels, and M-mode echocardiography. M-mode echocardiograms adequate to assess LV hypertrophy were obtained for 1,282 normotensive subjects (538 men and 744 women) and 79 subjects with isolated systolic hypertension (26 men and 53 women). Adjusting for age, body mass index and diastolic blood pressure, the relative odds of LV hypertrophy associated with isolated systolic hypertension were 2.58 (95% confidence interval 0.97 to 6.86) in men and 5.94 (95% confidence interval 3.06 to 11.53) in women. Women with isolated systolic hypertension had increased LV wall thickness and mass without LV chamber enlargement, but men had LV dilation and increased LV mass without increased wall thickness. In conclusion, although isolated systolic hypertension was associated with increased LV mass in men and women, the geometric pattern of increased LV mass differed by sex; although women demonstrated a pattern of concentric hypertrophy, an eccentric pattern was observed in men. C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY,5 THURBER ST,FRAMINGHAM,MA 01701. NHLBI,BETHESDA,MD 20892. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT MED,DIV CARDIOVASC,BOSTON,MA 02215. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT MED,DIV CLIN EPIDEMIOL,BOSTON,MA 02215. NR 32 TC 161 Z9 167 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 1 PY 1993 VL 72 IS 3 BP 310 EP 313 DI 10.1016/0002-9149(93)90678-6 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LP453 UT WOS:A1993LP45300011 PM 8342510 ER PT J AU FERNICOLA, DJ ROBERTS, WC AF FERNICOLA, DJ ROBERTS, WC TI FREQUENCY OF RING ABSCESS AND CUSPAL INFECTION IN ACTIVE INFECTIVE ENDOCARDITIS INVOLVING BIOPROSTHETIC VALVES SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID NECROPSY PATIENTS AB When active infective endocarditis (IE) involves a bioprosthetic valve, the infective process may involve only the cusps or sewing ring or both. We studied 34 patients with infected bioprostheses to determine whether the infection involved the cusps or ring, or both, because these locations could affect prognosis. In the 5 patients in whom active IE began <60 days after operation, the infection involved the cusps only in 2, the ring only in 2, and both in 1. The 29 patients in whom signs and symptoms of active IE appeared >60 days after valve replacement were subdivided into 3 categories based on the valve or valves In the 16 patients with isolated aortic valve replacement, the infection involved the cusps only in 6, the ring only in 4, and both in 6. In the 6 patients with isolated mitral valve replacement, the infection involved the cusps only in 2, the ring only in 1, and both in 3. In the remaining 7 patients, 15 native valves were replaced with bioprostheses, and 10 of them were infected. The infection involved the cusps only in 7, and both the cusps and ring in 3. Of all 34 patients, 13 had operative excision of the infected bioprosthesis: 1 died within 60 days of the bioprosthetic excision, and 1 was lost to follow-up; of the remaining 11 patients, 4 died late (1.5, 3, 5 and 14 years), and the other 7 are alive 5 to 10 years after bioprosthetic excision (all in New York Heart Association functional class I or II). Thus, although infection limited to the bioprosthetic cusps may reasonably allow a better outlook, reoperation with infection involving the annular ring (8 of 13 reoperation patients) does not prevent successful outcome. C1 NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. NR 12 TC 24 Z9 25 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 AUG 1 PY 1993 VL 72 IS 3 BP 314 EP 323 DI 10.1016/0002-9149(93)90679-7 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LP453 UT WOS:A1993LP45300012 PM 8342511 ER PT J AU MARON, BJ HECHT, G KLUES, HG KUNKES, SH ROSENFELD, LE CECCHI, F AF MARON, BJ HECHT, G KLUES, HG KUNKES, SH ROSENFELD, LE CECCHI, F TI BOTH ABORTED SUDDEN CARDIAC DEATH AND END-STAGE PHASE IN HYPERTROPHIC CARDIOMYOPATHY SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Note ID ARREST C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. BRIDGEPORT HOSP,DIV CARDIOL,BRIDGEPORT,CT 06610. YALE UNIV,SCH MED,CARDIOVASC MED SECT,NEW HAVEN,CT 06510. NR 8 TC 5 Z9 5 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 AUG 1 PY 1993 VL 72 IS 3 BP 363 EP 365 DI 10.1016/0002-9149(93)90690-E PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LP453 UT WOS:A1993LP45300023 PM 8342522 ER PT J AU SHIRANI, J BARRON, MM PIERRELOUIS, MLY ROBERTS, WC AF SHIRANI, J BARRON, MM PIERRELOUIS, MLY ROBERTS, WC TI CONGESTIVE-HEART-FAILURE, DILATED CARDIAC VENTRICLES, AND SUDDEN-DEATH IN HYPERTHYROIDISM SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Note ID HYPERTROPHIC CARDIOMYOPATHY; CATS; THYROTOXICOSIS C1 DIST COLUMBIA MED EXAMINERS OFF,WASHINGTON,DC. PROVIDENCE HOSP,DEPT EMERGENCY,SOUTHFIELD,MI 48037. RP SHIRANI, J (reprint author), NHLBI,PATHOL BRANCH,BETHESDA,MD 20892, USA. NR 24 TC 31 Z9 31 U1 1 U2 6 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 AUG 1 PY 1993 VL 72 IS 3 BP 365 EP 368 DI 10.1016/0002-9149(93)90691-5 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LP453 UT WOS:A1993LP45300024 PM 8342523 ER PT J AU SHIRANI, J ZAFARI, AM ROBERTS, WC AF SHIRANI, J ZAFARI, AM ROBERTS, WC TI SUDDEN-DEATH, RIGHT-VENTRICULAR INFARCTION, AND ABNORMAL RIGHT-VENTRICULAR INTRAMURAL CORONARY-ARTERIES IN ISOLATED CONGENITAL VALVULAR PULMONIC STENOSIS SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Note RP SHIRANI, J (reprint author), NHLBI,PATHOL BRANCH,BLDG 10,ROOM 2N258,BETHESDA,MD 20892, USA. NR 3 TC 4 Z9 4 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 AUG 1 PY 1993 VL 72 IS 3 BP 368 EP 370 DI 10.1016/0002-9149(93)90692-6 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LP453 UT WOS:A1993LP45300025 PM 8342524 ER PT J AU FLEGAL, KM LAUNER, LJ GRAUBARD, BI KESTLER, E VILLAR, J AF FLEGAL, KM LAUNER, LJ GRAUBARD, BI KESTLER, E VILLAR, J TI MODELING MATERNAL WEIGHT AND HEIGHT IN STUDIES OF PREGNANCY OUTCOME AMONG HISPANIC WOMEN SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE ANTHROPOMETRY; BIRTH WEIGHT; BODY HEIGHT; BODY MASS INDEX; BODY WEIGHT; CENTRAL AMERICA; EPIDEMIOLOGIC METHODS; GUATEMALA; HISPANIC AMERICANS; MEXICAN AMERICANS; PREGNANCY OUTCOME ID BODY-MASS INDEXES; BIRTH-WEIGHT; BENN INDEX; DETERMINANTS; OBESITY AB The objective of this study was to evaluate methods of using maternal weight and height in studies of pregnancy outcome for Hispanic women. Reference anthropometric data came from 1166 Mexican-American women in the Hispanic Health and Nutrition Examination Survey (HHANES). Prospective data on maternal anthropometry and infant birth weight came from 1362 Hispanic women in the Kaiser-Permanente Contraceptive Drug Study and 12 786 women in the Guatemalan Cooperative Perinatal Study. Five methods of standardizing weight for height were evaluated, including power-type indexes and weights relative to HHANES reference data. In linear- and logistic-regression analyses, these methods were practically interchangeable, with no evident advantage of Hispanic reference data. However, if weight was not height-standardized the effect of height was underestimated; if height was omitted and weight was not height-standardized the effects of weight were exaggerated. Therefore, analyses of pregnancy outcome should include both height and height-standardized weight. C1 NICHHD,PREVENT RES PROGRAM,BETHESDA,MD. GYNECOL & OBSTET HOSP,GUATEMALAN SOCIAL SECUR INST,PERINATAL RES PROGRAM,GUATEMALA CITY,GUATEMALA. RP FLEGAL, KM (reprint author), CTR DIS CONTROL & PREVENT,NATL CTR HLTH STAT,6525 BELCREST RD,ROOM 900,HYATTSVILLE,MD 20782, USA. RI Flegal, Katherine/A-4608-2013; OI Flegal, Katherine/0000-0002-0838-469X NR 23 TC 16 Z9 16 U1 0 U2 1 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD AUG PY 1993 VL 58 IS 2 BP 145 EP 151 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA LP776 UT WOS:A1993LP77600006 PM 8338040 ER PT J AU TRAVIS, LB HOLOWATY, E HUNTER, V BANERJEE, D JONES, TG LI, CY AF TRAVIS, LB HOLOWATY, E HUNTER, V BANERJEE, D JONES, TG LI, CY TI ACUTE BASOPHILIC LEUKEMIA AND ACUTE EOSINOPHILIC LEUKEMIA AFTER THERAPY FOR NON-HODGKIN-LYMPHOMA SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Letter ID ACUTE NONLYMPHOCYTIC LEUKEMIA; DIFFERENTIATION C1 ONTARIO CANC TREATMENT & RES FDN, TORONTO, ON, CANADA. PRINCESS MARGARET HOSP, TORONTO M4X 1K9, ONTARIO, CANADA. OTTAWA CIVIC HOSP, OTTAWA K1Y 4E9, ONTARIO, CANADA. MAYO CLIN & MAYO FDN, ROCHESTER, MN 55905 USA. RP TRAVIS, LB (reprint author), NCI, BETHESDA, MD 20892 USA. NR 6 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 EI 1943-7722 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD AUG PY 1993 VL 100 IS 2 BP 186 EP 186 PG 1 WC Pathology SC Pathology GA LT764 UT WOS:A1993LT76400021 PM 8257517 ER PT J AU AKSENTIJEVICH, I PRAS, E GRUBERG, L SHEN, Y HOLMAN, K HELLING, S PROSEN, L SUTHERLAND, GR RICHARDS, RI RAMSBURG, M DEAN, M PRAS, M AMOS, CI KASTNER, DL AF AKSENTIJEVICH, I PRAS, E GRUBERG, L SHEN, Y HOLMAN, K HELLING, S PROSEN, L SUTHERLAND, GR RICHARDS, RI RAMSBURG, M DEAN, M PRAS, M AMOS, CI KASTNER, DL TI REFINED MAPPING OF THE GENE CAUSING FAMILIAL MEDITERRANEAN FEVER, BY LINKAGE AND HOMOZYGOSITY STUDIES SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID HUMAN CHROMOSOME-16; POLYMORPHIC LOCI; SHORT ARM; MAP; DNA; MARKERS; LOCALIZATION; ARMENIANS AB Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by attacks of fever and serosal inflammation; the biochemical basis is unknown. We recently reported linkage of the gene causing FMF (designated ''MEF'') to two markers on chromosome 16p. To map MEF more precisely, we have now tested nine 16p markers. Two-point and multipoint linkage analysis, as well as a study of recombinant haplotypes, placed MEF between D16S94 and D16S80, a genetic interval of about 9 cM. We also examined rates of homozygosity for markers in this region, among offspring of consanguineous marriages. For eight of nine markers, the rate of homozygosity among 26 affected inbred individuals was higher than that among their 20 unaffected sibs. Localizing MEF more precisely on the basis of homozygosity rates alone would be difficult, for two reasons: First, the high FMF carrier frequency increases the chance that inbred offspring could have the disease without being homozygous by descent at MEF. Second, several of the markers in this region are relatively nonpolymorphic, with a high rate of homozygosity, regardless of their chromosomal location. C1 NIAMDD,ARTHRITIS & RHEUMATISM BRANCH,BLDG 6,ROOM 112,BETHESDA,MD 20892. CHAIM SHEBA MED CTR,DEPT MED F,IL-52621 TEL HASHOMER,ISRAEL. CHAIM SHEBA MED CTR,HELLER INST MED RES,IL-52621 TEL HASHOMER,ISRAEL. ADELAIDE CHILDRENS HOSP INC,DEPT CYTOGENET & MOLEC GENET,ADELAIDE,SA 5006,AUSTRALIA. NCI,FREDERIC CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. NIAMDD,SKIN BIOL LAB,BETHESDA,MD 20892. RI Sutherland, Grant/D-2606-2012; Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 30 TC 30 Z9 31 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD AUG PY 1993 VL 53 IS 2 BP 451 EP 461 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA LN820 UT WOS:A1993LN82000017 PM 8328461 ER PT J AU STEENLAND, K SILVERMAN, D AF STEENLAND, K SILVERMAN, D TI 2ND-HAND SMOKE AMONG LONG-HAUL TRUCK DRIVERS SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Letter DE DIESEL EXHAUST EXPOSURES; LUNG CANCER RISK; NONSMOKERS ID LUNG-CANCER C1 NCI,BETHESDA,MD 20892. RP STEENLAND, K (reprint author), NIOSH,INDUSTRYWIDE STUDIES BRANCH,R-13,4676 COLUMBIA PKWY,CINCINNATI,OH 45116, USA. NR 3 TC 2 Z9 2 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 AUG PY 1993 VL 24 IS 2 BP 259 EP 259 DI 10.1002/ajim.4700240217 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA LN838 UT WOS:A1993LN83800016 ER PT J AU PICCHIO, GR COHEN, JI WYATT, ER MOSIER, DE AF PICCHIO, GR COHEN, JI WYATT, ER MOSIER, DE TI ENHANCED TUMORIGENICITY OF AN EPSTEIN-BARR VIRUS-TRANSFORMED LYMPHOBLASTOID CELL-LINE IS ASSOCIATED WITH A UNIQUE 1-18 CHROMOSOMAL TRANSLOCATION AND DECREASED EXPRESSION OF LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1A (CD11A) SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Note ID SEVERE COMBINED IMMUNODEFICIENCY; LYMPHOPROLIFERATIVE DISORDERS; NUCLEAR PROTEIN-2; IMMUNE-SYSTEM; SCID MICE; LYMPHOMAS; LATENT; GENE; TRANSPLANTATION; TERMINI AB An Epstein-Barr virus-transformed lymphoblastoid cell line was identified that disseminated to multiple organs and grew rapidly when transplanted to severe combined immunodeficient mice. This pattern of growth more closely resembled that of Burkitt's lymphoma cells than that of all other lymphoblastoid cell lines tested. Analysis of the rapidly growing lymphoblastoid cell line showed two distinctive changes. First, all of the cells derived from the tumor had a 1:18 chromosomal translocation [t(1;18)(p32.1;q23.3)]. Second, the lymphoblastoid cell line down-regulated expression of lympbocyte function associated antigen-1a during passage in severe combined immunodeficient mice. but regained expression upon growth in vitro. These two changes seem sufficient to explain the enhanced tumorigenicity of this cell line and may represent examples of changes that lead to more aggressive lymphomas in posttransplant lymphoproliferative disease. C1 MED BIOL INST,DIV IMMUNOL,BETHESDA,MD. NIH,CLIN INVEST LAB,BETHESDA,MD 20892. FU NIAID NIH HHS [AI22871, AI29182] NR 32 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD AUG PY 1993 VL 143 IS 2 BP 342 EP 349 PG 8 WC Pathology SC Pathology GA LQ675 UT WOS:A1993LQ67500004 PM 8393615 ER PT J AU WARE, RE PARKER, RI MCKEOWN, LP GRAHAM, ML AF WARE, RE PARKER, RI MCKEOWN, LP GRAHAM, ML TI A HUMAN CHIMERA FOR VON-WILLEBRAND DISEASE FOLLOWING BONE-MARROW TRANSPLANTATION SO AMERICAN JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE VON-WILLEBRAND DISEASE; VON-WILLEBRAND FACTOR; BLEEDING DISORDER; BONE MARROW TRANSPLANTATION; HUMAN CHIMERA ID VIII-RELATED ANTIGEN; BLEEDING-TIME; HUMAN MEGAKARYOCYTES; PLATELET-ADHESION; BLOOD-PLATELETS; PLASMA; FIBRINOGEN; MULTIMERS; COLLAGEN; PIG AB Purpose: von Willebrand disease (vWD) is a common bleeding disorder characterized by quantitative or qualitative defects in von Willebrand factor (vWF), a protein important for coagulation and platelet adhesion. There are two forms of vWF currently recognized: plasma vWF synthesized by endothelial cells and platelet vWF produced within megakaryocytes. Although both plasma and platelet vWF play important roles in overall hemostasis, the relative contribution of each form is not clear. Patients and Methods: We report the results of bone marrow transplantation from a donor with Type I vWD into a hemostatically normal recipient. Results: Following engraftment, the recipient appears to be a human chimera for vWD, with normal amounts of plasma vWF from endogenous endothelial cells, but low levels of platelet vWF derived from donor megakaryocytes. Conclusions: Although the vWD chimerism has not been associated with any clinical manifestations, the bleeding time has become prolonged, suggesting that platelet vWF is important for normalization of the bleeding time. C1 DUKE UNIV,MED CTR,PEDIAT BONE MARROW TRANSPLANTAT PROGRAM,DURHAM,NC 27710. NIH,CTR CLIN,DEPT CLIN PATHOL,HEMATOL SERV,BETHESDA,MD 20892. RP WARE, RE (reprint author), DUKE UNIV,MED CTR,DIV PEDIAT HEMATOL ONCOL,POB 2916,DURHAM,NC 27710, USA. NR 27 TC 9 Z9 11 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0192-8562 J9 AM J PEDIAT HEMATOL PD AUG PY 1993 VL 15 IS 3 BP 338 EP 342 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA LN050 UT WOS:A1993LN05000014 PM 8328650 ER PT J AU RABKIN, R TSAO, T ELLIOT, SJ STRIKER, LJ STRIKER, GE AF RABKIN, R TSAO, T ELLIOT, SJ STRIKER, LJ STRIKER, GE TI INSULIN UPTAKE AND PROCESSING BY CULTURED MOUSE GLOMERULAR ENDOTHELIAL-CELLS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE KIDNEY; INSULIN TRANSPORT; INSULIN DEGRADATION; EXOCYTOSIS ID DEGRADATION; RECEPTOR; RETROENDOCYTOSIS; INTERNALIZATION; BINDING; LINE; METABOLISM; TRANSPORT; CAPILLARY; MUSCLE AB Endothelial cells isolated from a variety of vascular beds bind and transport insulin but exhibit relatively low insulin degrading activity. Because endothelial cells exhibit heterogeneity and since kidney is a major site of insulin degradation, we studied the processing of insulin by glomerular endothelial cells (GEC). When exposed to 2 x 10(-10) M I-125-labeled insulin, GEC associated with the hormone in a specific manner. This interaction was inhibited by insulin but not by a number of unrelated peptide hormones. Over a 90-min period, GEC degraded 42 +/- 3% of the I-125-insulin, as measured by solubility in trichloroacetic acid (TCA). Degradation was inhibited 90% by an excess of insulin or adrenocorticotropic hormone (10(-6) M) and 57% by glucagon, whereas growth hormone and calcitonin were without effect. Separation of plasma membrane bound from internalized insulin was achieved by decreasing extracellular pH. In the steady state, 43% of cell-associated insulin was membrane bound and 57% internalized. The fate of the internalized I-125-insulin was examined by incubating acid-washed cells at 37-degrees-C for 60 min. Over this time 18% of the radioactivity was released as TCA insoluble- and 72% as TCA-soluble radioactivity. Release was increased by insulin (10(-6) M) but not by unrelated peptide hormones. In the presence of chloroquine, I-125-insulin release increased by one third while degradation fell. High-performance liquid chromatography revealed that GEC released both intact insulin and large intermediates and that chloroquine inhibited intermediate formation. We conclude that endothelial cells possess insulin-specific receptors that mediate hormone internalization. Internalized insulin is then processed either through a major chloroquine-sensitive degradative pathway or a lesser exocytosis pathway that returns intact and partially cleaved insulin to the extracellular compartment. Thus GEC share the same two pathways common to endothelial cells from other vascular beds. However, unlike these other endothelial cells that have minor insulin-degrading activity, in GEC the degradative pathway predominates. C1 NIDDKD,METAB DIS BRANCH,RENAL CELL BIOL GRP,BETHESDA,MD 20892. RP RABKIN, R (reprint author), STANFORD UNIV,SCH MED,VET ADM MED CTR 154L,3801 MIRANDA AVE,PALO ALTO,CA 94304, USA. FU NIDDK NIH HHS [DK-32342] NR 35 TC 7 Z9 7 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD AUG PY 1993 VL 265 IS 2 BP C453 EP C459 PN 1 PG 7 WC Physiology SC Physiology GA LW031 UT WOS:A1993LW03100019 PM 8368274 ER PT J AU CIUFFO, GM VISWANATHAN, M SELTZER, AM TSUTSUMI, K SAAVEDRA, JM AF CIUFFO, GM VISWANATHAN, M SELTZER, AM TSUTSUMI, K SAAVEDRA, JM TI GLOMERULAR ANGIOTENSIN-II RECEPTOR SUBTYPES DURING DEVELOPMENT OF RAT-KIDNEY SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE ANGIOTENSIN-II; AT(1)-RECEPTOR SUBTYPE; AT(2)-RECEPTOR SUBTYPE; KIDNEY DEVELOPMENT; ORGANOGENESIS ID BASEMENT-MEMBRANE; MESSENGER-RNA; EXPRESSION; AUTORADIOGRAPHY; LOCALIZATION; HYPERTROPHY; LAMININ; GROWTH; CELLS; FETUS AB We used quantitative autoradiography to investigate distribution of angiotensin II (ANG II) receptor subtypes during development of the kidney in the rat. In fetal, newborn, and 3-day-old rats, immature glomeruli in the form of comma and S-shaped bodies, located in the nephrogenic zone of the renal cortex, expressed only the angiotensin AT2 receptor subtype. Conversely, the juxtamedullary glomeruli, in more advanced developmental stages, expressed only the AT1 subtype. Similarly, maturing and fully developed glomeruli, present in l-, 2-, and 8-wk-old rats, expressed only AT1 receptors. In the kidney medulla, there was a similar change in ANG II receptor subtype expression, with the AT2 subtype expressed earlier and the AT1 subtype later during development. Our results demonstrate a selective expression of ANG II receptor subtypes during kidney development. We have found glomerular and medullary AT1 receptors only at developmental stages when kidney function has matured. Conversely, AT2 receptors are expressed only in immature structures, suggesting that they may have a role during kidney organogenesis. RP CIUFFO, GM (reprint author), NIMH,CLIN SCI LAB,PHARMACOL SECT,BLDG 10,RM 2D-45,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 26 TC 90 Z9 90 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD AUG PY 1993 VL 265 IS 2 BP F264 EP F271 PN 2 PG 8 WC Physiology SC Physiology GA LW032 UT WOS:A1993LW03200090 PM 8368335 ER PT J AU KNEPPER, MA NIELSEN, S AF KNEPPER, MA NIELSEN, S TI KINETIC-MODEL OF WATER AND UREA PERMEABILITY REGULATION BY VASOPRESSIN IN COLLECTING DUCT SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE EXOCYTOSIS; ENDOCYTOSIS; WATER CHANNEL; UREA CARRIER ID ANTIDIURETIC-HORMONE; ENDOCYTOSIS; TUBULE; ADH AB We present a mathematical model describing the kinetics of water-channel and urea-carrier regulation by vasopressin in the apical membrane of collecting duct cells. The rate of change of the number of activated channels or carriers in the apical membrane is modeled as a balance between the rate of activation (or exocytic insertion) and the rate of inactivation (or endocytic retrieval) of transporters. In a three-state version of the model, transporters are assumed to be partitioned into three physical states, i.e., an 'activated'' state that imparts a permeation pathway to the apical membrane, an ''inactivated'' state, and a ''reserve'' state. Both activation and inactivation are represented by first-order kinetic equations describing transition from reserve to activated transporters and from activated to inactivated transporters, respectively. A simplified two-state model is derived from the three-state model, with the assumption that the transformation from inactivated to reserve transporter occurs rapidly relative to the other state transitions. Simulated time courses obtained by solving model equations are compared with experimentally determined time courses to test whether the response to vasopressin in isolated inner medullary collecting duct segments can be explained by direct effects on the rate constants for activation or inactivation. The results indicate that, for both transporters, it must be assumed that vasopressin directly regulates rate constants for both activation (exocytosis) and inactivation (endocytosis) to account for the experimentally determined dynamic responses to vasopressin and its withdrawal. These studies provide a theoretical basis on which to design further experimental studies. RP KNEPPER, MA (reprint author), NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BLDG 10,ROOM 6N307,BETHESDA,MD 20892, USA. NR 19 TC 45 Z9 45 U1 1 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 AUG PY 1993 VL 265 IS 2 BP F214 EP F224 PN 2 PG 11 WC Physiology SC Physiology GA LW032 UT WOS:A1993LW03200085 PM 8396343 ER PT J AU NIELSEN, S KNEPPER, MA AF NIELSEN, S KNEPPER, MA TI VASOPRESSIN ACTIVATES COLLECTING DUCT UREA TRANSPORTERS AND WATER CHANNELS BY DISTINCT PHYSICAL PROCESSES SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE RAT; ADENOSINE 3',5'-CYCLIC MONOPHOSPHATE; RENAL MEDULLA; SKF-105494 ID TOAD URINARY-BLADDER; ANTIDIURETIC-HORMONE; PERMEABILITY; ENDOCYTOSIS; HYDROOSMOSIS; PERMEATION; MECHANISMS; TUBULES; CALCIUM; ADH AB The present studies were performed to investigate the kinetics of regulation of water channels and urea carriers in the rat terminal (IMCD) in response to vasopressin (AVP). The time courses of osmotic water permeability (P(f)) and urea permeability (P(urea)) were measured in isolated perfused rat terminal IMCD segments following AVP stimulation and subsequently following AVP washout. Under control conditions, P(f) and P(urea) kinetics were similar. Both transport processes exhibited complex patterns of activation with a period of rapid permeability increase followed by a period of slower increase. Both transporters also exhibited complex patterns of reversal following AVP washout, with a rapid permeability decrease (5 min) followed by a slower decrease toward the baseline value. The measurements were repeated in the presence of a lumen>bath osmotic gradient, a condition associated with a decreased rate of apical endocytosis in collecting ducts. The lumen>bath gradient did not alter the kinetics of P(f) increase after AVP addition, but completely blocked the decrease in P(f) normally seen with washout of AVP. In contrast, the lumen>bath osmotic gradient did not affect the decrease in urea permeability after AVP washout, but blocked the rapid phase of urea permeability increase following AVP addition. Thus imposition of a lumen>bath osmotic gradient resulted in separation of the time courses of P(urea) and P(f) changes associated with AVP addition and washout. This finding indicates that the physical processes responsible for AVP-mediated alteration of urea transporter and water channel activity in the apical membrane are distinct. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BLDG 10,ROOM 6N307,BETHESDA,MD 20892. NR 27 TC 90 Z9 91 U1 1 U2 5 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 AUG PY 1993 VL 265 IS 2 BP F204 EP F213 PN 2 PG 10 WC Physiology SC Physiology GA LW032 UT WOS:A1993LW03200084 PM 8396342 ER PT J AU NIELSEN, S MULLER, J KNEPPER, MA AF NIELSEN, S MULLER, J KNEPPER, MA TI VASOPRESSIN-INDUCED AND CAMP-INDUCED CHANGES IN ULTRASTRUCTURE OF ISOLATED-PERFUSED INNER MEDULLARY COLLECTING DUCTS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE ELECTRON MICROSCOPY; COLLECTING DUCT ULTRASTRUCTURE; OSMOTIC WATER PERMEABILITY; COATED PITS; ENDOCYTOSIS ID TOAD URINARY-BLADDER; PAPILLARY SURFACE EPITHELIUM; ADH-INDUCED VACUOLES; WATER PERMEABILITY; ANTIDIURETIC-HORMONE; APICAL MEMBRANE; COATED PITS; RAT-KIDNEY; UREA; ENDOCYTOSIS AB Studies were performed to correlate arginine vasopressin (AVP)-induced changes in epithelial ultrastructure with changes in osmotic water permeability in isolated perfused rat terminal inner medullary collecting ducts (tIMCD). The tubules were perfused in three time periods, i.e., a 40-min basal period, a 40-min period with 0.1 nM AVP in the bath, and a 60-min withdrawal period. In each phase, the osmotic water permeability (P(f)) was measured, and the perfused tubules were fixed for electron microscopy. AVP caused a four- to eightfold increase in P(f) and induced several ultrastructural changes as follows: increased cell height of IMCD cells, expansion of the intercellular spaces, formation of large vacuoles, and increased coated pit density in the apical plasma membrane [from 0.6 +/- 0.2 (n = 6) to 2.9 +/- 0.3 (n = 7) pits/100 mum membrane length]. During AVP withdrawal, P(f) decreased toward the basal value in association with partial reversal of the ultrastructural changes including a decrease in coated pit density to 1.0 +/- 0.2 (n = 4). Stimulation with 8-bromoadenosine 3',5'-cyclic monophosphate (8-bromo-cAMP) (0.1 mM) produced similar changes in P(f). Coated pit density increased to 2.1 +/- 0.4 (n = 4) after CAMP stimulation and after cAMP withdrawal decreased to 1.2 +/- 0.2 (n = 6). In contrast to stimulation with AVP, cAMP stimulation did not result in dilated intercellular spaces or formation of large vacuoles. The only ultrastructural feature that directly correlated with the water permeability was the density of coated pits in the apical membrane. Organelles involved in the endocytic pathway were studied with cationized ferritin or albumin-gold in the luminal perfusate. At the end of 40 min basal perfusion or AVP stimulation, luminal tracer was found almost exclusively in large multivesicular bodies (MVB). Tubules perfused with tracer during AVP withdrawal demonstrated rapid tracer accumulation in small vesicles and small MVB within 3-5 min, a time point corresponding to the rapid phase of P(f) decrease. Later (30-60 min) the label was mainly confined to large MVB. Occasionally during AVP stimulation or withdrawal, small coated vesicles and smooth vesicles with coated extensions were noted to contain tracer. The data demonstrate AVP-mediated coated pit formation and cellular changes and show very rapid internalization of apical membrane after AVP withdrawal. C1 US FDA,CTR BIOL EVALUAT & RES,DIV BIOCHEM & BIOPHYS,BETHESDA,MD 20892. RP NIELSEN, S (reprint author), NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BLDG 10,ROOM 6N307,BETHESDA,MD 20892, USA. NR 38 TC 41 Z9 41 U1 1 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 AUG PY 1993 VL 265 IS 2 BP F225 EP F238 PN 2 PG 14 WC Physiology SC Physiology GA LW032 UT WOS:A1993LW03200086 PM 8396344 ER PT J AU DUBELL, WH LEWARTOWSKI, B SPURGEON, HA SILVERMAN, HS LAKATTA, EG AF DUBELL, WH LEWARTOWSKI, B SPURGEON, HA SILVERMAN, HS LAKATTA, EG TI REPLETION OF SARCOPLASMIC RETICULUM-CA AFTER RYANODINE IN RAT VENTRICULAR MYOCYTES SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE EXCITATION-CONTRACTION COUPLING; CAFFEINE; INDO-1; ISOPROTERENOL; THAPSIGARGIN ID RAPID COOLING CONTRACTURES; CA-2+ RELEASE CHANNEL; GUINEA-PIG HEART; CARDIAC MYOCYTES; CALCIUM RELEASE; REST DECAY; MUSCLE; RABBIT; ACTIVATION; MECHANISM AB The ryanodine (R)-induced loss of sarcoplasmic reticulum (SR) Ca2+ and the abilities of the SR to accumulate Ca2+ and participate in contractile activation after R were studied in rat ventricular myocytes. Indo 1 fluorescence (IF) indexed cytosolic Ca2+, and caffeine assayed SR Ca2+. Before R, there was a negative staircase, and the SR accumulated Ca2+ at rest. During stimulation (0.5 Hz), R decreased IF and contraction, converting the negative staircase to positive. When R was pulsed onto resting cells, IF increased and cells shortened, subsequently behaving as if stimulated in R. After R, there was no caffeine-releasable Ca2+ at rest, and little accumulated during 0.5-Hz stimulation. At high rates, caffeine-releasable Ca2+ and diastolic IF increased. In isoproterenol and R, IF transients and contractions recovered at 0.5 Hz with a marked positive staircase and little diastolic IF increase. Within 10 beats, SR Ca2+ accumulated to pre-R levels. R eliminated the positive inotropic effect of paired-pulse stimulation, but isoproterenol temporarily restored it. Twitch contractions in thapsigargin, an SR Ca2+ pump blocker, and isoproterenol were slow compared with control or R+ isoproterenol. R leaks SR Ca2+ into the cytosol. SR Ca2+ can be repleted in R by high-rate stimulation or by low-rate stimulation with a beta-adrenergic agonist. SR Ca2+ release in R can be temporarily restored if Ca2+ influx and SR Ca2+ pumping are increased enough to overcome the SR Ca2+ leak. C1 CARIOL FDN LANKENAU,WYNNEWOOD,PA 19096. NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224. NR 39 TC 26 Z9 26 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 AUG PY 1993 VL 265 IS 2 BP H604 EP H615 PN 2 PG 12 WC Physiology SC Physiology GA LW032 UT WOS:A1993LW03200025 PM 8368363 ER PT J AU JANCZEWSKI, AM LAKATTA, EG AF JANCZEWSKI, AM LAKATTA, EG TI THAPSIGARGIN INHIBITS CA2+ UPTAKE, AND CA2+ DEPLETES SARCOPLASMIC-RETICULUM IN INTACT CARDIAC MYOCYTES SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE EXCITATION-CONTRACTION COUPLING; INDO-1; CAFFEINE; RYANODINE ID CA-2+ RELEASE CHANNEL; SELECTIVE MICROELECTRODES; VENTRICULAR MUSCLE; THAPSIA-GARGANICA; RYANODINE; RAT; CALCIUM; ACTIVATION; CONTRACTION; TRANSIENT AB We examined the effects of thapsigargin on Ca2+ accumulation by the sarcoplasmic reticulum (SR) and on electrically stimulated beats in single adult rat ventricular myocytes loaded with indo 1 and bathed in N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid buffer containing 1 mM Ca2+ at 23-degrees-C. The SR Ca2+ content was assessed from the magnitude of intracellular Ca2+ (Ca(i)2+) transients and contractions elicited by rapid, brief applications of caffeine. After 20-30 min of exposure to 200 nM thapsigargin, the caffeine-dependent Ca(i)2+ transients were abolished or markedly diminished (by 89 +/- 4%). The postrest potentiation of the Ca(i)2+ transient and contraction, typical for rat myocardium, was abolished. Thapsigargin did not significantly change resting Ca2+ but diminished the amplitude of the steady-state Ca2+ transients by 73%, prolonged the time to peak by 24%, and prolonged the half-time (t1/2) of the Ca(i)2+ transient decline by 42%. Progressive SR Ca2+ depletion by thapsigargin was strongly related (r = -0.78) to the prolongation of the t1/2 of relaxation of the steady-state Ca(i)2+ transients, suggesting that the thapsigargin-dependent SR Ca2+ depletion results from an inhibition of the SR Ca2+ uptake. This interpretation was corroborated by comparison of the effects of thapsigargin with those of ryanodine (100 nM), which depletes SR of Ca2+ by accelerating the SR Ca2+ efflux but does not inhibit the SR Ca2+ pump. During rapid pacing (5 Hz), which raises Ca(i)2+ and thus Ca2+ available for SR uptake, the caffeine-dependent SR Ca2+ release was restored in ryanodine-treated cells but not in the presence of thapsigargin. Thus, in contrast to ryanodine, thapsigargin prevents SR Ca2+ uptake, consistent with an inhibition of the SR Ca2+ pump. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224. NR 25 TC 59 Z9 59 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 AUG PY 1993 VL 265 IS 2 BP H517 EP H522 PN 2 PG 6 WC Physiology SC Physiology GA LW032 UT WOS:A1993LW03200013 PM 8368355 ER PT J AU WINOKUR, G CORYELL, W ENDICOTT, J AKISKAL, H AF WINOKUR, G CORYELL, W ENDICOTT, J AKISKAL, H TI FURTHER DISTINCTIONS BETWEEN MANIC-DEPRESSIVE ILLNESS (BIPOLAR DISORDER) AND PRIMARY DEPRESSIVE DISORDER (UNIPOLAR DEPRESSION) SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID MAJOR DEPRESSION; FAMILY; PROBANDS AB Objective: Patients with bipolar disorder differ from patients with unipolar depression by having family histories of mania with an earlier onset and by having more episodes over a life-time. This study was designed to determine whether additional aspects of course of illness, the presence of medical diseases, childhood traits, and other familial illnesses separate the two groups. Method: In a large collaborative study, consecutively admitted bipolar and unipolar patients were systematically given clinical interviews. Data were collected on medical diseases and childhood behavioral traits. Systematic family history and family study data were also obtained. The patients were studied every 6 months for 5 years. Results: The group of bipolar patients had an earlier onset, a more acute onset, more total episodes, and more familial mania and were more likely to be male. These differences were relatively independent of each other. The bipolar patients were also more likely to have shown traits of hyperactivity as children. The unipolar patients had a significantly greater number of lifetime medical/surgical interventions than the bipolar patients, even when age was controlled. Alcoholism was more frequently found in the families of the bipolar patients, even when alcoholism in the probands was controlled, however, this difference was not significant. Conclusions: This study supports the usefulness of distinguishing between bipolar and unipolar patients in treatment and research studies. C1 NIMH,COLLABORAT PROGRAM PSYCHOBIOL DEPRESS CLIN STUDIES,BETHESDA,MD 20892. NR 25 TC 145 Z9 146 U1 0 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 1993 VL 150 IS 8 BP 1176 EP 1181 PG 6 WC Psychiatry SC Psychiatry GA LP806 UT WOS:A1993LP80600007 PM 8328560 ER PT J AU GFROERER, JC BRODSKY, MD AF GFROERER, JC BRODSKY, MD TI FREQUENT COCAINE USERS AND THEIR USE OF TREATMENT SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID ILLICIT DRUG-USE; UNITED-STATES AB Objectives. Despite decreases in the number of cocaine users since 1985, the consequences of cocaine use continue to rise. This paper provides descriptive data on frequent cocaine users that will help to explain these diverging trends and enable treatment planners to better predict the types of cocaine users who are likely to seek treatment. Methods. Data from the National Household Survey on Drug Abuse were used to study the characteristics of frequent cocaine users since 1985. The 1991 data were used to compare frequent users with infrequent users and nonusers. Results. Since 1985, frequent cocaine users have become older. In 1991, they were likely to be unemployed (32.4%), unmarried (82.3%), and without health insurance (39.4%). Most were cigarette smokers (86.8%) and marijuana users (88.4%), and 32.0% reported getting drunk weekly. Criminal behavior was more likely among frequent cocaine users than among infrequent users and nonusers. Almost a third (30.0%) reported drug abuse treatment experience in the past year. Conclusions. Despite the recent decreases in overall prevalence of cocaine use, the need for treatment of cocaine abusers will continue. Treatment must address multiple problems that occur in conjunction with cocaine abuse. C1 NIDA,ROCKVILLE,MD. NR 29 TC 23 Z9 23 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD AUG PY 1993 VL 83 IS 8 BP 1149 EP 1154 DI 10.2105/AJPH.83.8.1149 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA LR018 UT WOS:A1993LR01800017 PM 8342725 ER PT J AU KVALE, PA ROSEN, MJ HOPEWELL, PC MARKOWITZ, N HANSEN, N REICHMAN, LB WALLACE, JM GLASSROTH, J FULKERSON, W MEISELMAN, L AF KVALE, PA ROSEN, MJ HOPEWELL, PC MARKOWITZ, N HANSEN, N REICHMAN, LB WALLACE, JM GLASSROTH, J FULKERSON, W MEISELMAN, L TI A DECLINE IN THE PULMONARY DIFFUSING-CAPACITY DOES NOT INDICATE OPPORTUNISTIC LUNG-DISEASE IN ASYMPTOMATIC PERSONS INFECTED WITH THE HUMAN-IMMUNODEFICIENCY-VIRUS SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; IMMUNE-DEFICIENCY SYNDROME; NONSPECIFIC INTERSTITIAL PNEUMONITIS; FUNCTION TESTS; DIAGNOSIS; VALUES AB We enrolled 1,353 subjects in a multicenter study to evaluate the spectrum of pulmonary complications associated with human immunodeficiency virus (HIV) infection and the feasibility of detecting pulmonary infections in asymptomatic members of this group. There were 1,171 who were HIV-seropositive; the remaining 182 were HIV-seronegative, but they belonged to high-risk transmission groups (homosexual/bisexual, or injection drug users). Single-breath carbon monoxide diffusing capacity (DL(CO)) WaS Measured serially (at 3- to 12-month intervals) in a prospective fashion to determine whether a decline of greater-than-or-equal-to 20% predicted the presence of Pneumocystis carinii pneumonia or other pulmonary infections in the absence of new pulmonary symptoms and no new abnormalities on chest roentgenograms. In 64 subjects (6% of the group who had two or more measurements) DL(CO) declined greater-than-or-equal-to 20% from a prior value within 2 yr of entry, unassociated with fever, increased cough or dyspnea, or new chest roentgenogram abnormalities. Induced sputum was analyzed for the presence of P. carinii and mycobacteria in 44; fiberoptic bronchoscopy was performed with bronchoalveolar lavage in 14, six of whom also had transbronchial lung biopsy. All 64 subjects with the asymptomatic decline in DL(CO) were followed for an additional 3 to 12 months with additional clinical evaluations, chest roentgenograms, and DL(CO) determinations, or until death (one subject). In no case was the decline in DL(CO) due to P. carinii pneumonia or other pulmonary infection. Two subjects were found to have nonspecific interstitial pneumonitis by transbronchial lung biopsy; none had this disorder confirmed by open lung biopsy or autopsy, and no patient developed a clinical/roentgenographic picture that was suggestive of nonspecific interstitial pneumonitis. Eight subjects were thought to have a reduced DL(CO) because they were unable to perform the test properly. Of the 63 subjects for whom follow-up DL(CO) measurements were available, improvement was noted in 45 (71%); DL(CO) remained stable in seven (11%), and DL(CO) declined further in 11 (17%). Nonspecific interstitial pneumonitis or lymphocytic alveolitis may have caused the asymptomatic decline of DL(CO) in HIV-infected subjects. An alternative explanation is the amount of intraindividual variability of the test. We conclude that a decline in the DL(CO) without concomitant respiratory symptoms or new chest roentgenographic abnormalities does not warrant further evaluation. Moreover, serial measurements of DL(CO) should not be performed to screen HIV-infected persons for lung diseases. C1 NHLBI,DIV LUNG DIS,BETHESDA,MD 20892. NIAID,BETHESDA,MD 20892. FU NHLBI NIH HHS [N01-HR7-6029, N01-HR7-6031, N01-HR7-6030] NR 22 TC 17 Z9 17 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD AUG PY 1993 VL 148 IS 2 BP 390 EP 395 PG 6 WC Respiratory System SC Respiratory System GA LQ605 UT WOS:A1993LQ60500019 PM 8102043 ER PT J AU PEDEN, DB SWIERSZ, M OHKUBO, K HAHN, B EMERY, B KALINER, MA AF PEDEN, DB SWIERSZ, M OHKUBO, K HAHN, B EMERY, B KALINER, MA TI NASAL SECRETION OF THE OZONE SCAVENGER URIC-ACID SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Article ID EPITHELIAL LINING FLUID; LOWER RESPIRATORY-TRACT; BRONCHIAL RESPONSIVENESS; ALLERGIC SUBJECTS; PATHO-PHYSIOLOGY; INFLAMMATION; RHINITIS; HUMANS; RESPONSES; ANTIGEN AB Uric acid, an important scavenger of ozone, has been identified as the major low molecular weight antioxidant in baseline and cholinergically induced nasal secretions. The purpose of this study was to determine the specific tissue source of uric acid in airway secretions. The secretion of uric acid is increased by cholinergic stimulation and correlates closely with the secretion of lactoferrin (a nasal glandular protein), suggesting that submucosal glands are involved. Indeed, nasal turbinate tissue was found to contain uric acid. However, careful analysis of nasal turbinate tissue failed to reveal the presence of xanthine oxidase, the enzyme responsible for uric acid synthesis. These data suggest that uric acid might be taken up secondarily by glands from plasma. This possibility was strengthened by the observation that lowering the plasma urate level with probenecid concomitantly lowered urate secretion. These findings are consistent with the hypotheses that the principal source of uric acid in nasal secretions is plasma and that uric acid is taken up, concentrated, and secreted by nasal glands. C1 RUSH MED SCH,CHICAGO,IL. NIAID,CTR CLIN,NURSING SERV,BETHESDA,MD 20892. NIPPON MED COLL,DEPT OTORHINOLARYNGOL,TOKYO 113,JAPAN. NIAID,CLIN INVEST LAB,ALLERG DIS SECT,BETHESDA,MD 20892. UNIV N CAROLINA,CTR ENVIRONM MED & LUNG BIOL,SCH MED,CHAPEL HILL,NC 27599. RP PEDEN, DB (reprint author), UNIV N CAROLINA,SCH MED,DEPT PEDIAT,CB 7310,CHAPEL HILL,NC 27599, USA. NR 23 TC 38 Z9 40 U1 1 U2 3 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD AUG PY 1993 VL 148 IS 2 BP 455 EP 461 PG 7 WC Respiratory System SC Respiratory System GA LQ605 UT WOS:A1993LQ60500030 PM 8342911 ER PT J AU ZIMMERMAN, SB MURPHY, LD AF ZIMMERMAN, SB MURPHY, LD TI QUANTITATION OF REACTIONS BY REFERENCE TO MAXIMAL PEAK VALUES RATHER THAN TO BASE-LINE VALUES SO ANALYTICAL BIOCHEMISTRY LA English DT Note RP ZIMMERMAN, SB (reprint author), NIDDKD,MOLEC BIOL LAB,ROOM 328W,BLDG 5,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD AUG 1 PY 1993 VL 212 IS 2 BP 566 EP 567 DI 10.1006/abio.1993.1372 PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA LR019 UT WOS:A1993LR01900039 PM 8214604 ER PT J AU LEAK, LV JONES, M AF LEAK, LV JONES, M TI LYMPHATIC ENDOTHELIUM ISOLATION, CHARACTERIZATION AND LONG-TERM CULTURE SO ANATOMICAL RECORD LA English DT Article DE LYMPHATIC ENDOTHELIUM; CELL CULTURE; FACTOR-VIII-RELATED ANTIGEN; ACTIN FILAMENTS; ANCHORING FILAMENTS ID FIBROBLAST GROWTH-FACTOR; ULTRASTRUCTURAL-LOCALIZATION; TISSUE-CULTURE; CELLS; ANTIGEN; PROTEIN; GOLGI AB Using a collagenase trypsin-EDTA treatment, we have been able to successfully isolate and grow primary cultures of the lymphatic endothelium (LEC) that were subcultured, frozen for storage, subsequently thawed with good recovery and growth, and serially subcultured. The morphological features of cultured LEC were consistent with that observed the endothelium of intact lymphatic vessels. A prominent feature of growing cultures was the appearance of large vacuoles in the perinuclear region of the cytoplasm, which became filled with fluid and cell debris engulfed from the culture medium. The basal cell surface lacked a well defined basal lamina and anchoring filaments were observed extending from the basal plasmalemmal surface into the underlying substratum. LEC in cultures were also positive for Factor VIII-related antigen. However, specific granules, characteristic of Weibel-Palade bodies were not observed in ultrathin sections of confluent cultures. F-actin was identified in LEC cultures using fluorescein phalloidin, and in confluent cultures actin filaments were located at the periphery of the cell as a continuous circumferential thin band and short filamentous bundles in the central part of the cell. By using heparin and endothelial cell growth supplement in the culture medium we have been able to grow stable cultures of lymphatic endothelial cells that could be maintained when serially subcultured for over two years. These LEC cultures provide an in vitro model for investigating the function and biochemical properties of the lymphatic endothelium. (C) 1993 Wiley-Liss, Inc. C1 NHLBI,ANIM MED & SURG LAB,BETHESDA,MD 20892. RP LEAK, LV (reprint author), HOWARD UNIV,COLL MED,DEPT ANAT,ERNEST E JUST LAB CELLULAR BIOL,WASHINGTON,DC 20059, USA. NR 43 TC 32 Z9 43 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0003-276X J9 ANAT REC JI Anat. Rec. PD AUG PY 1993 VL 236 IS 4 BP 641 EP 652 DI 10.1002/ar.1092360408 PG 12 WC Anatomy & Morphology SC Anatomy & Morphology GA LQ122 UT WOS:A1993LQ12200007 PM 8379589 ER PT J AU BRINGMANN, G ZAGST, R SCHAFFER, M HALLOCK, YF CARDELLINA, JH BOYD, MR AF BRINGMANN, G ZAGST, R SCHAFFER, M HALLOCK, YF CARDELLINA, JH BOYD, MR TI THE ABSOLUTE-CONFIGURATION OF MICHELLAMINE-B, A DIMERIC, ANTI-HIV-ACTIVE NAPHTHYLISOQUINOLINE ALKALOID SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH LA English DT Article ID ACETOGENIC ISOQUINOLINE ALKALOIDS; ANCISTROCLADUS-ABBREVIATUS AB Ruthenium-mediated oxidative degradation led to the elucidation of the absolute configuration of michellamine B (1), the most active representative of a new class of naturally occurring ''dimeric'' naphthylisoquinolinealkaloids. Based on the degradation products. D-alanine and the (R)-3-aminobutyric acid, and the fact that the relative configurations of the stereocenters and the axis within the two molecular ''halves'' is known, 1 is deduced to have a (1R,3 R,5 M,1''' R,3'' R,5''' P) configuration. C1 NCI,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21702. RP BRINGMANN, G (reprint author), UNIV WURZBURG,INST ORGAN CHEM,HUBLAND,D-97074 WURZBURG,GERMANY. NR 12 TC 51 Z9 51 U1 0 U2 2 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0570-0833 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. Engl. PD AUG PY 1993 VL 32 IS 8 BP 1190 EP 1191 DI 10.1002/anie.199311901 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA LU338 UT WOS:A1993LU33800029 ER PT J AU HERSHFIELD, B CHADER, G AGUIRRE, G AF HERSHFIELD, B CHADER, G AGUIRRE, G TI CLONING OF A POLYMORPHIC CANINE GENETIC-MARKER WHICH MAPS TO HUMAN CHROMOSOME-9 SO ANIMAL GENETICS LA English DT Note DE DOG; GENETICS; CHROMOSOMAL EVOLUTION; POLYMORPHISM ID DNA; DOGS; REGION; ARM AB We describe the cloning of a novel canine polymorphic genetic marker which maps to human chromosome 9. The sequence is 2092 bp, 59% GC rich, and contains three GC boxes. Chemiluminescent probing of zooblots showed evolutionary conservation. Dogs have three Bam HI alleles: 2.3 kb, 2.1 kb and 1.7 kb. Allele frequencies in 17 unrelated dogs representing 13 breeds are presented. Polymorphism for the 1.7-kb allele in beagles is common. The 2.1-kb allele is probably the ancestral allele since it is the most common and is also noted in the Cape hunting dog. Interestingly, in more than 50 dogs tested to date, the 2.3-kb allele has been found only in miniature and giant schnauzers. This points to a common origin for these two breeds. C1 NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. RP HERSHFIELD, B (reprint author), CORNELL UNIV,JAMES A BAKER INST ANIM HLTH,CTR CANINE GENET & REPROD,ITHACA,NY 14853, USA. FU NEI NIH HHS [NEI EY01244, NEI EY06855] NR 10 TC 2 Z9 2 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0268-9146 J9 ANIM GENET JI Anim. Genet. PD AUG PY 1993 VL 24 IS 4 BP 293 EP 295 PG 3 WC Agriculture, Dairy & Animal Science; Genetics & Heredity SC Agriculture; Genetics & Heredity GA LU718 UT WOS:A1993LU71800011 PM 7916582 ER PT J AU HIBBS, JR CEGLOWSKI, WS GOLDBERG, M KAUFFMAN, F AF HIBBS, JR CEGLOWSKI, WS GOLDBERG, M KAUFFMAN, F TI EMERGENCY DEPARTMENT-BASED SURVEILLANCE FOR SYPHILIS DURING AN OUTBREAK IN PHILADELPHIA SO ANNALS OF EMERGENCY MEDICINE LA English DT Article AB Study objective: To identify missed opportunities for syphilis treatment during an outbreak. Design: Prospective prevalence survey. Setting: Urban hospital emergency department. Participants: Nine hundred sixty-one persons aged 15 to 44 years seeking medical attention in the ED who were not suspected of having any sexually transmitted disease (STD) at the time of their visit. Intervention: Serologic testing for syphilis and public health follow-up as needed. Measurements and main results: Twenty-one non-STD patients (2%) had untreated early syphilis, and 22 (2%) had positive serology but were lost to follow-up. Among 271 STD patients seen in the ED during the same period, 15 cases (6%) were detected. We estimate that 80 or more additional untreated early syphilis cases would have been identified had all 15- to 44-year-old patients entering the ED been tested. The cost of screening was $251 per case detected. Conclusion: Patients not suspected of having any STD account for most early syphilis cases among all ED patients. Screening and on-site treatment for syphilis should be offered to all young adults seeking medical attention in the ED during syphilis outbreaks. RP HIBBS, JR (reprint author), NHLBI,CHB,BLDG 10,ROOM 7C103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 16 Z9 16 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD AUG PY 1993 VL 22 IS 8 BP 1286 EP 1290 DI 10.1016/S0196-0644(05)80108-8 PG 5 WC Emergency Medicine SC Emergency Medicine GA LN989 UT WOS:A1993LN98900008 PM 8333629 ER PT J AU FISHBEYN, VA NORTON, JA BENYA, RV PISEGNA, JR VENZON, DJ METZ, DC JENSEN, RT AF FISHBEYN, VA NORTON, JA BENYA, RV PISEGNA, JR VENZON, DJ METZ, DC JENSEN, RT TI ASSESSMENT AND PREDICTION OF LONG-TERM CURE IN PATIENTS WITH THE ZOLLINGER-ELLISON SYNDROME - THE BEST APPROACH SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE ZOLLINGER-ELLISON SYNDROME; GASTRINOMA; SECRETIN; GASTRIC ACIDITY DETERMINATION; GASTRIN ID ISLET CELL TUMORS; GASTRINOMAS; MANAGEMENT; RESECTION; LOCALIZATION; DIAGNOSIS; ANGIOGRAPHY; EXCISION; SECRETIN; SURGERY AB Objective: To identify the best method for determining freedom from disease after gastrinoma resection and for predicting long-term disease-free status in patients with the Zollinger-Ellison syndrome. Design: Prospective study in consecutive patients. Setting: Referral-based clinical research center. Patients: Eighty-one consecutive patients with the Zollinger-Ellison syndrome who underwent surgical exploration for gastrinoma resection. Intervention: Patients were evaluated after gastrinoma resection, before discharge, 3 to 6 months after surgery, and yearly thereafter. Evaluation included secretin provocative testing and fasting serum gastrin determinations. Follow-up examinations after the initial postoperative evaluations included a clinical assessment, acid secretion studies, a calcium provocative test, and various imaging studies. Measurements and Main Results. Most patients (96%) had gastrinomas. Freedom from disease was defined by improved symptoms, reduced acid output and antisecretory drug requirements, and a normal gastrin level, normal imaging studies, and negative gastrin provocative studies. Fifty-two percent of patients (n = 42) were disease-free immediately after surgery, 44% at 3 to 6 months, 42% at 1 year, and 35% by 5 years (mean follow-up, 39 months). The secretin provocative test was the first test to become positive in 45% of patients with a recurrence, the serum gastrin determination was the first test to become positive in 36%, and both tests became positive at the same time in 18%. No recurrence was first detected by imaging studies or by calcium provocative testing. Fasting serum gastrin levels and secretin provocative test results at different postoperative times can be used to predict the probability of a patient remaining disease free at 3 years. Patients with a normal gastrin level and a normal secretin provocative test immediately after surgery had a 3-year disease-free probability of 75%, and normal results on both tests at 6 months, 1 year, and 2 years yielded respective probabilities of 88%, 95%, and 100%. Conclusions: Both the secretin provocative test and fasting serum gastrin determination are necessary for the early diagnosis of cases of recurrent disease after gastrinoma resection. The calcium provocative test and imaging studies do not detect any recurrences first. Fasting serum gastrin determinations and secretin provocative testing at different postoperative times can be used to predict the probability of a patient remaining disease free at 3 years. C1 NIH,BLDG 10,ROOM 9C-103,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 50 TC 101 Z9 102 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 AUG 1 PY 1993 VL 119 IS 3 BP 199 EP 206 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA LU903 UT WOS:A1993LU90300004 PM 8323088 ER PT J AU CHANSON, P WEINTRAUB, BD HARRIS, AG AF CHANSON, P WEINTRAUB, BD HARRIS, AG TI OCTREOTIDE THERAPY FOR THYROID-STIMULATING HORMONE-SECRETING PITUITARY-ADENOMAS - A FOLLOW-UP OF 52 PATIENTS SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID ACTING SOMATOSTATIN ANALOG; SMS 201-995; INAPPROPRIATE SECRETION; GROWTH-HORMONE; THYROTROPIN; SMS-201-995; TSH; IMPROVEMENT; INHIBITION; RECEPTORS AB Objective: To evaluate the efficacy of octreotide in the treatment of pituitary thyroid-stimulating hormone (TSH)-secreting adenomas. Data Sources. Combination of review and original data. Review data included information supplied by Sandoz Pharmaceuticals from patient case report forms and information from abstracts and articles published in the French or English language between 1987 and 1991. Original data included follow-up data on 15 of 37 previously reported cases and data on 15 new cases provided by 11 investigators. Study Selection: Fifty-two cases from 24 medical centers in nine countries reported between 1987 and 1991. Data Extraction: Chief clinical characteristics of the patients; dose and duration of octreotide treatment; serum TSH, thyroid hormone, and free alpha-subunit levels before and during treatment; serial anatomic evaluation of the pituitary gland by either computed tomographic scanning or magnetic resonance imaging; and side effects. Data Synthesis: After the first octreotide dose (50 to 100 mug), TSH levels decreased in all but 2 patients (mean decrease for the whole group, 55.8% +/- 27%). Levels of alpha-subunit decreased in 15 of the 19 patients who had alpha-subunit assessments (mean decrease, 37.5% +/- 24%). Reduction of TSH levels after short-term treatment (50 or 100 mug two or three times daily) was observed in 30 of 33 patients (mean decrease, 74.1%). Thyroid hormone levels were reduced in all patients and returned to normal in 73%. Despite an initial response to therapy, thyroid hormone levels continued to rise (''true escape'') in 2 patients receiving short-term therapy and in 3 patients receiving long-term therapy. Partial shrinkage of the adenoma occurred in 11 patients. Conclusions: Octreotide is an effective treatment for TSH-secreting adenomas. Thyroid-stimulating hormone levels almost always decreased, and thyroid hormone levels reverted to normal in about three quarters of patients. Partial tumor shrinkage was observed in one third of patients receiving long-term octreotide treatment. C1 NIH,BETHESDA,MD 20892. CEDARS SINAI MED CTR,LOS ANGELES,CA 90048. RP CHANSON, P (reprint author), HOP LARIBOISIERE,DEPT INTERNAL MED & ENDOCRINOL,2 RUE AMBROISE PARE,F-75475 PARIS 10,FRANCE. RI Chanson, Philippe/F-8511-2013; OI Harris, Alan/0000-0002-6618-2092 NR 38 TC 150 Z9 152 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 AUG 1 PY 1993 VL 119 IS 3 BP 236 EP 240 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA LU903 UT WOS:A1993LU90300010 PM 8323093 ER PT J AU ZURLO, JJ POLIS, MA MASUR, H AF ZURLO, JJ POLIS, MA MASUR, H TI HOW USEFUL ARE CYTOMEGALOVIRUS CULTURES IN PATIENTS WITH HIV-INFECTION - RESPONSE SO ANNALS OF INTERNAL MEDICINE LA English DT Letter ID HUMAN-IMMUNODEFICIENCY-VIRUS; PREDICTIVE VALUE C1 NIAID,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. RP ZURLO, JJ (reprint author), PENN STATE UNIV,MILTON S HERSHEY MED CTR,HERSHEY,PA 17033, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 1 PY 1993 VL 119 IS 3 BP 248 EP 249 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA LU903 UT WOS:A1993LU90300020 ER PT J AU DECARLI, C CIVITELLO, LA BROUWERS, P PIZZO, PA AF DECARLI, C CIVITELLO, LA BROUWERS, P PIZZO, PA TI THE PREVALENCE OF COMPUTED TOMOGRAPHIC ABNORMALITIES OF THE CEREBRUM IN 100 CONSECUTIVE CHILDREN SYMPTOMATIC WITH THE HUMAN IMMUNE-DEFICIENCY VIRUS SO ANNALS OF NEUROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CEREBROSPINAL-FLUID; HIV-INFECTION; PROGRESSIVE ENCEPHALOPATHY; AIDS ENCEPHALOPATHY; PEDIATRIC AIDS; ALZHEIMER TYPE; III INFECTION; RELIABILITY; INVOLVEMENT AB Qualitative analysis of 100 consecutive computed tomographic (CT) studies of the brain in children with symptomatic but untreated acquired immunodeficiency syndrome was performed. After excluding children with associated medical illnesses that might confound the diagnosis of encephalopathy or alter brain structure, an abnormality of at least one of the measures of ventricular size, cortical atrophy, white matter attenuation (leukoaraiosis), or cerebral calcification was found in 86% of the patients studied. Ventricular enlargement was the most common abnormality, followed by cortical atrophy, leukoaraiosis, and cerebral calcification. Cerebellar atrophy was an unexpected but relatively common finding in 12% of the children. Sixty-five percent of the children were encephalopathic at the time of evaluation. All 16 children with cerebral calcification were encephalopathic and had acquired human immunodeficiency virus (HIV) through vertical transmission. Encephalopathic children were significantly younger and had significantly greater abnormality ratings on each CT measure when compared with the nonencephalopathic children. Discriminant analysis using age and the qualitative CT measures was applied as a method to identify the presence of encephalopathy. CT measures proved to have a specificity and a sensitivity of only 76%. We conclude that abnormalities of cerebral structure are seen in a high percentage of children symptomatic with HIV. Although most of the children are encephalopathic, CT abnormalities are seen in children without encephalopathy, suggesting presymptomatic brain disease. The presence of cerebral calcification on CT suggests in utero infection with HIV and the presence of encephalopathy. Although not diagnostic of encephalopathy, routine use of CT in pediatric patients with acquired immunodeficiency syndrome may add significant additional information about the mode of HIV transmission and potential presymptomatic brain disease. C1 NCI,PEDIAT BRANCH,BLDG 10,ROOM 13N 240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. CHILDRENS NATL MED CTR,WASHINGTON,DC. NIA,NEUROSCI LAB,BETHESDA,MD 20892. RI DeCarli, Charles/B-5541-2009 NR 44 TC 70 Z9 72 U1 0 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD AUG PY 1993 VL 34 IS 2 BP 198 EP 205 DI 10.1002/ana.410340216 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA LR024 UT WOS:A1993LR02400014 PM 8338344 ER PT J AU SUGG, SL NORTON, JA FRAKER, DL METZ, DC PISEGNA, JR FISHBEYN, V BENYA, RV SHAWKER, TH DOPPMAN, JL JENSEN, RT AF SUGG, SL NORTON, JA FRAKER, DL METZ, DC PISEGNA, JR FISHBEYN, V BENYA, RV SHAWKER, TH DOPPMAN, JL JENSEN, RT TI A PROSPECTIVE-STUDY OF INTRAOPERATIVE METHODS TO DIAGNOSE AND RESECT DUODENAL GASTRINOMAS SO ANNALS OF SURGERY LA English DT Article ID ZOLLINGER-ELLISON SYNDROME; LOCALIZATION; TUMORS; MANAGEMENT AB Objective This study determined, prospectively, whether duodenotomy (DX) should be routinely performed in explorations for patients with Zollinger-Ellison syndrome (ZES). Summary Background Data Duodenal gastrinomas are now being found with increasing frequency in patients with Zollinger-Ellison syndrome. The surgical approach used to detect these tumors is controversial. Some recommend intraoperative endoscopy with transillumination (IOE) at surgery, while others recommend routine DX. Methods Beginning in 1989, the authors prospectively compared the ability of palpation, intraoperative ultrasound (IOUS), IOE, and DX (in that sequence) to detect gastrinomas in 35 consecutive patients with ZES. Each patient also underwent preoperative localization studies. Results Thirty-three of 35 patients (94%) had tumor detected and excised; duodenal gastrinomas were excised in 27 patients (77%). The average size of the duodenal tumors was 0.8 cm, significantly smaller (p < 0.005) than the pancreatic and lymph node tumors in this series. Standard palpation after a Kocher maneuver identified 19 of the 31 duodenal tumors (61%) in the 27 patients. IOUS revealed only eight duodenal tumors (26%) and no new lesions. IOE identified 20 duodenal gastrinomas (64%) and 6 new lesions. DX identified 31 duodenal tumors (100%) and 5 additional tumors. The morbidity rate was 17%. One patient had a duodenal fistula after operation (2.8%) and subsequently recovered. No patient died. Conclusions These results demonstrate that the duodenum is the most common location for gastrinoma in patients with ZES (77%) and that DX to detect and remove duodenal gastrinomas should be routinely performed in all explorations for patients with ZES. C1 NCI,SURG BRANCH,SURG METAB SECT,BETHESDA,MD 20892. NIADDKD,CTR CLIN,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NIADDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892. NR 19 TC 110 Z9 113 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD AUG PY 1993 VL 218 IS 2 BP 138 EP 144 DI 10.1097/00000658-199308000-00004 PG 7 WC Surgery SC Surgery GA LR022 UT WOS:A1993LR02200005 PM 8342993 ER PT J AU DRAKE, JC ALLEGRA, CJ JOHNSON, PG AF DRAKE, JC ALLEGRA, CJ JOHNSON, PG TI IMMUNOLOGICAL QUANTITATION OF THYMIDYLATE SYNTHASE FDUMP-5,10-METHYLENETETRAHYDROFOLATE TERNARY COMPLEX WITH THE MONOCLONAL-ANTIBODY TS-106 SO ANTI-CANCER DRUGS LA English DT Article DE 5-FLUOROURACIL; MONOCLONAL ANTIBODY; THYMIDYLATE SYNTHASE ID SYNTHETASE; 5-FLUORO-2'-DEOXYURIDYLATE; CANCER; 5-FLUOROURACIL AB Thymidylate synthase (TS) is responsible for the conversion of deoxyuridine monophosphate to deoxythymidine monophosphate. One of the principal mechanisms of action of 5-fluorouracil (5-FU) is the inhibition of TS by formation of a ternary covalent complex consisting of TS-5-fluorodeoxyuridylate-5,10-methylenetetrahydrofolate. We have developed a Western immunoblot assay using the monoclonal antibody TS 106 to measure ternary complex and free TS in intact human carcinoma cells following exposure to either 5-FU alone or 5-FU plus leucovorin. Lysates from cells treated with either 5-FU or 5-FU/leucovorin were resolved in 15% polyacrylamide gel, transferred onto nitrocellulose and immunoblotted using TS 106 antibody. Detection of positive bands was by a chromogenic substrate strain. Immunoblotting detected free TS at 36 kDa and TS in ternary complex at 38.5 kDa which were quantitated by densitometric scanning. This assay was able to detect a ternary complex from intact cells treated with 5-FU or 5FU/leucovorin up to 96 h after drug removal. The ratio of complex to free TS was up to 2-fold greater in 5-FU/leucovorin-treated cells compared to those treated with 5-FU alone. This assay may be applied to measuring the formation and stability of ternary complex and free TS in patient tissue samples. RP DRAKE, JC (reprint author), USN,HOSP MED,NCI,MED ONCOL BRANCH,BLDG 8,ROOM 5101,BETHESDA,MD 20889, USA. NR 14 TC 14 Z9 14 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD AUG PY 1993 VL 4 IS 4 BP 431 EP 435 DI 10.1097/00001813-199308000-00002 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA LU455 UT WOS:A1993LU45500002 PM 8400344 ER PT J AU MARTINEZ, A KOVACS, JA AF MARTINEZ, A KOVACS, JA TI DEVELOPMENT AND CHARACTERIZATION OF A RAPID SCREENING ASSAY FOR IDENTIFYING ANTIPNEUMOCYSTIS AGENTS SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HUMAN PNEUMOCYSTIS-CARINII; SURFACE GLYCOPROTEIN; RAT; ANTIBODIES; ANTIGENS; GROWTH; CULTURE; INVITRO; A549 AB We developed a rapid assay for screening of compounds with potential antipneumocystis activity on the basis of incorporation of [S-35]methionine into proteins newly synthesized by Pneumocystis carinii. Unambiguous evidence that P. carinii synthesizes proteins in vitro was provided by immunoprecipitation studies demonstrating the incorporation of [S-25]methionine into the major surface glycoprotein. Treatment with two clinically active antipneumocystis agents, atovaquone (10(-4) M) or pentamidine (10(-4) M), prevented this incorporation. Total [S-35]methionine incorporation paralleled incorporation into the major surface glycoprotein, permitting rapid assessment of anti-P. carinii activity by scintillation counting. Treatment with pentamidine (1 x 10(-4) M), atovaquone, trimethoprim (1 X 10(-4) M)-sulfamethoxazole (7.9 x 10(-4) M), piritrexim (1 X 10(-7) M), RO11-8958 (1 X 10(-4) M), and amphotericin B (1 mug/ml) resulted in a greater than 67% inhibition (P < 0.05) of [S-35]methionine incorporation. No decrease in [S-35]methionine incorporation was seen with dapsone (10(-5) M), trimethoprim (10(-4) M), recombinant mouse tumor necrosis factor (500 ng/ml), or gamma interferon. This rapid in vitro assay should be a useful adjunct in the development of new antipneumocystis agents. RP MARTINEZ, A (reprint author), NIH,DEPT CRIT CARE MED,CTR CLIN,BETHESDA,MD 20892, USA. NR 23 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 1993 VL 37 IS 8 BP 1674 EP 1678 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA LP793 UT WOS:A1993LP79300021 PM 8215282 ER PT J AU RYAN, R GRIMM, SW KEDZIE, KM HALPERT, JR PHILPOT, RM AF RYAN, R GRIMM, SW KEDZIE, KM HALPERT, JR PHILPOT, RM TI CLONING, SEQUENCING, AND FUNCTIONAL-STUDIES OF PHENOBARBITAL-INDUCIBLE FORMS OF CYTOCHROME-P450-2B AND CYTOCHROME-P450-4B EXPRESSED IN RABBIT KIDNEY SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID SPECIES-DEPENDENT EXPRESSION; MONO-OXYGENASE SYSTEM; AMINO-ACID; RAT-LIVER; NUCLEOTIDE-SEQUENCES; CATALYTIC ACTIVITY; RIBONUCLEIC-ACID; GENE SUBFAMILY; CDNA; ISOZYME-5 C1 NIEHS,CELLULAR & MOLEC PHARMACOL,POB 12233,RES TRIANGLE PK,NC 27709. UNIV ARIZONA,COLL PHARM,DEPT PHARMACOL & TOXICOL,TUCSON,AZ 85721. UNIV N CAROLINA,TOXICOL PROGRAM,CHAPEL HILL,NC 27599. FU NIEHS NIH HHS [ES 04995, F32 ES 05502] NR 41 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 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD AUG 1 PY 1993 VL 304 IS 2 BP 454 EP 463 DI 10.1006/abbi.1993.1375 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LN806 UT WOS:A1993LN80600022 PM 8346920 ER PT J AU HSIAO, JK COLISON, J BARTKO, JJ DORAN, AR KONICKI, PE POTTER, WZ PICKAR, D AF HSIAO, JK COLISON, J BARTKO, JJ DORAN, AR KONICKI, PE POTTER, WZ PICKAR, D TI MONOAMINE NEUROTRANSMITTER INTERACTIONS IN DRUG-FREE AND NEUROLEPTIC-TREATED SCHIZOPHRENICS SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID PLASMA HOMOVANILLIC-ACID; CEREBROSPINAL-FLUID; 5-HYDROXYINDOLEACETIC ACID; PSYCHOTIC-PATIENTS; BRAIN RECEPTORS; CSF; METABOLITES; DOPAMINE; NOREPINEPHRINE; ANTIDEPRESSANTS AB Objective: To study recent suggestions by a number of investigators that interactions between monoamine neurotransmitter systems play an important role in schizophrenia. It has not been clear how hypotheses about interactions might be tested in clinical data. One means for indexing interactions between monoamine neurotransmitter systems may be to compare correlations between cerebrospinal fluid (CSF) monoamine metabolite (homovanillic acid [HVA], 5-hydroxyindoleacetic acid [5-HIAA], and 3-methoxy-4-hydroxyphenylglycol [MHPG]) or ratios of these metabolites (HVA/5-HIAA and HVA/MHPG). Design: We compared these putative measures of monoamine neurotransmitter interaction in 50 drug-free patients with schizophrenia (hospitalized on an inpatient ward of a tertiary care hospital) and 33 normal controls and examined the effects of neuroleptic antipsychotic treatment on these measures in 41 patients (22 of whom had antecedent drug-free CSF data). Results: Drug-free patients with schizophrenia had significantly smaller correlations between CSF monoamine metabolites than normal controls. Longer drug-free time was associated with even smaller correlations between metabolites, suggesting that the difference between controls and patients was not due to acute drug withdrawal. After treatment with neuroleptic antipsychotics there were significant increases in the HVA/5-HIAA and HVA/MHPG ratios, as well as increases in correlations between monoamine metabolites. After treatment, there were no significant differences in metabolite correlations between patients and controls. Metabolite ratios and correlations did not predict subsequent treatment response, but preliminary analyses demonstrated negative relationships between HVA/5-HIAA and HVA/MHPG ratios and Brief Psychiatric Rating Scale rating at that time. Conclusions: The present findings are consistent with and support hypotheses suggesting that interactions between monoamine systems are altered in schizophrenia and that antipsychotic treatment may affect the functional balance between different monoamine neurotransmitters (although one should keep in mind factors other than interactions between monoamine systems that affect metabolite correlations and ratios). C1 NIMH,DIV APPL & SERV RES,BETHESDA,MD 20892. CANYON SPRINGS HOSP,PALM SPRINGS,CA. CASE WESTERN RESERVE UNIV,DEPT PSYCHIAT,CLEVELAND,OH 44106. RP HSIAO, JK (reprint author), NIMH,EXPTL THERAPEUT BRANCH,CLIN PHARMACOL SECT,BLDG 10,ROOM 4N214,BETHESDA,MD 20892, USA. NR 57 TC 38 Z9 39 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 1993 VL 50 IS 8 BP 606 EP 614 PG 9 WC Psychiatry SC Psychiatry GA LR487 UT WOS:A1993LR48700002 PM 7688209 ER PT J AU HIGLEY, JD THOMPSON, WW CHAMPOUX, M GOLDMAN, D HASERT, MF KRAEMER, GW SCANLAN, JM SUOMI, SJ LINNOILA, M AF HIGLEY, JD THOMPSON, WW CHAMPOUX, M GOLDMAN, D HASERT, MF KRAEMER, GW SCANLAN, JM SUOMI, SJ LINNOILA, M TI PATERNAL AND MATERNAL GENETIC AND ENVIRONMENTAL CONTRIBUTIONS TO CEREBROSPINAL-FLUID MONOAMINE METABOLITES IN RHESUS-MONKEYS (MACACA-MULATTA) SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID HOMOVANILLIC-ACID; PRIMATE MODEL; PLASMA; CSF; DEPRESSION; BRAIN; PERSONALITY; SEROTONIN; 3-METHOXY-4-HYDROXYPHENYLGLYCOL; NOREPINEPHRINE AB Backgrounds: To study genetic and environmental contributions to cerebrospinal fluid (CSF) monoamine concentrations, 55 young rhesus monkeys (Macaca mulatta) were reared apart from their 10 fathers to perform a paternal half-sibling analysis. Methods: To study maternal genetic contributions, 23 infants were reared with their mothers, 23 infants were removed from their mothers at birth and fostered to unrelated lactating female monkeys, and 24 infants were removed from their mothers at birth and reared with age-matched peers. When the monkeys reached age 6 months, CSF samples were obtained via cisternal puncture prior to and during a series of social separations. Results: When the results were statistically pooled according to the biological father, comparisons using analysis of variance indicated that both CSF 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) concentrations showed significant heritable (h2) effects (h2>0.5) for both sons and daughters, whereas 3-methoxy-4-hydroxyphenylglycol (MHPG) showed a nearly significant paternal genetic effect only for sons (h2>0.5). in addition, there were substantial maternal genetic influences on the young monkeys' CSF MHPG and 5-HIAA (h2>0.5) levels. Structural equation analyses indicated a maternal genetic contribution without a maternal environmental contribution to CSF 5-HIAA concentration; on the other hand, there was both a maternal genetic and environmental contribution to MHPG. Conclusions: These findings suggest that a significant portion of the variance in the turnover of the monoamine neurotransmitters is determined by genetic mechanisms. C1 NIAAA,DICBR,CLIN STUDIES LAB,BETHESDA,MD. UNIV VIRGINIA,DEPT PSYCHOL,CHARLOTTESVILLE,VA 22903. UNIV WISCONSIN,HARLOW PRIMATE LAB,MADISON,WI 53706. RP HIGLEY, JD (reprint author), NIH ANIM CTR,NICHHD,COMPARAT ETHOL LAB,POB 529,BLDG 112,POOLESVILLE,MD 20837, USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 60 TC 191 Z9 193 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 1993 VL 50 IS 8 BP 615 EP 623 PG 9 WC Psychiatry SC Psychiatry GA LR487 UT WOS:A1993LR48700003 PM 7688210 ER PT J AU OWEN, RR GUTIERREZESTEINOU, R HSIAO, J HADD, K BENKELFAT, C LAWLOR, BA MURPHY, DL PICKAR, D AF OWEN, RR GUTIERREZESTEINOU, R HSIAO, J HADD, K BENKELFAT, C LAWLOR, BA MURPHY, DL PICKAR, D TI EFFECTS OF CLOZAPINE AND FLUPHENAZINE TREATMENT ON RESPONSES TO M-CHLOROPHENYLPIPERAZINE INFUSIONS IN SCHIZOPHRENIA SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; HUMAN-BRAIN INVITRO; META-CHLOROPHENYLPIPERAZINE; SEROTONIN AGONIST; NEURO-ENDOCRINE; RAT-BRAIN; NEUROTRANSMITTER RECEPTORS; ATYPICAL NEUROLEPTICS; MONOAMINE METABOLITES; CEREBROSPINAL-FLUID AB Objective: To explore serotonin function in patients with schizophrenia during typical and atypical neuroleptic treatment. We hypothesized that clinically relevant doses of the atypical neuroleptic clozapine would attenuate responses to the serotonin agonist m-chlorophenylpiperazine (m-CPP). Design and Interventions: m-CPP or placebo was administered intravenously over 90 seconds to patients who had been receiving no medications for at least 3 weeks. m-CPP was also administered during treatment with the typical neuroleptic fluphenazine and the atypical neuroleptic clozapine. Patients: Fifteen inpatients (two women and 13 men) who met DSM-III-R criteria for chronic schizophrenia (n=13) or schizoaffective disorder (n=2) participated in the study. Mean age (+/-SD) was 33.8+/-8.0 years. Main Outcome Measures: Measures of m-CPP effects included plasma cortisol and prolactin, body temperature, and the Brief Psychiatric Rating Scale (BPRS). The final BPRS total score at approximately 12 weeks of treatment was used to assess response to clozapine. Results: m-CPP infusion significantly increased plasma cortisol and prolactin levels in drug-free patients. There was a range of behavioral responses while drug-free, but no statistically significant effects on BPRS total or BPRS factor scores. Clozapine treatment significantly blocked neuroendocrine responses to m-CPP, whereas fluphenazine had no effect. Clozapine also appeared to attenuate behavioral responses. Conclusions: These results demonstrate that clozapine treatment has potent serotonin antagonist effects in patients with schizophrenia. This may be related to clozapine's therapeutic effects since patients with greater cortisol response to m-CPP while drug-free had a better subsequent response to clozapine. C1 NIMH,EXPTL THERAPEUT BRANCH,BLDG 10,ROOM 4N214,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT NURSING,BETHESDA,MD 20892. VET AFFAIRS MED CTR,LITTLE ROCK,AR. UNIV ARKANSAS MED SCI HOSP,DEPT PSYCHIAT,LITTLE ROCK,AR 72205. NR 61 TC 57 Z9 58 U1 2 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 1993 VL 50 IS 8 BP 636 EP 644 PG 9 WC Psychiatry SC Psychiatry GA LR487 UT WOS:A1993LR48700005 PM 8343034 ER PT J AU POTTER, WZ MANJI, HK AF POTTER, WZ MANJI, HK TI ARE MONOAMINE METABOLITES IN CEREBROSPINAL-FLUID WORTH MEASURING SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Note ID D-TYPE SCORES; RAT HIPPOCAMPUS; NOREPINEPHRINE; SUBGROUPS; DOPAMINE; INPUT RP POTTER, WZ (reprint author), NIMH,EXPTL THERAPEUT BRANCH,CLIN PHARMACOL SECT,BLDG 10,ROOM 2D46,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 36 TC 21 Z9 21 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 1993 VL 50 IS 8 BP 653 EP 656 PG 4 WC Psychiatry SC Psychiatry GA LR487 UT WOS:A1993LR48700007 PM 7688211 ER PT J AU POSTON, JM AF POSTON, JM TI PELCZARIA-AURANTIA GEN-NOV, SP-NOV, A NEWLY DESCRIBED ORANGE-COLORED BACTERIUM SO ARCHIVES OF MICROBIOLOGY LA English DT Article ID LIQUID-CHROMATOGRAPHY; ACID AB An organism from a goldfish aquarium, isolated on barbital medium, was found to be a Gram-positive coccus which divided in alternating planes, often appearing as a doublet or as a tetrad with adjacent sides flattened. It grew well, although slowly, on rich solid medium (LB agar) and in liquid brain-heart infusion at room temperature (ca. 22-degrees-C); growth was slower and less extensive at 30-degrees-C or 37-degrees-C. No growth was seen at 4-5-degrees-C or at 42-degrees-C. It withstands brief exposure to ultraviolet radiation. Its growth was inhibited by low levels (0.1 unit/ml) of penicillin but was unaffected by levels of acetazolamide in excess of 1 mg/ml, indicating that it lacks carbonic anhydrase. Acid was not produced from glucose, maltose, mannose, lactose, or sucrose and only weakly, if at all, from fructose. Its DNA has a G + C mol percent of 59 measured chromatographically and neither the DNA nor rRNA from the organism hybridized with DNA from any organism that seemed related on morphological or other bases. Thin-layer chromatography of chloroform: methanol extracts of the organism show that it contains phosphatidyl choline, phosphatidyl ethanolamine, and phosphatidyl glycerol. Cell-wall preparations contain glutamic acid, serine, histidine, lysine, and alanine in the ratio of 1 : 1 : 1 : 1 : 8. Colonies were red-orange in color due, in larger measure, to a carotenoid tentatively identified as rhodopin. The organism was named Pelczaria aurantia. RP POSTON, JM (reprint author), NHLBI,BIOCHEM LAB,BETHESDA,MD 20892, USA. NR 15 TC 3 Z9 3 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0302-8933 J9 ARCH MICROBIOL JI Arch. Microbiol. PD AUG PY 1993 VL 160 IS 2 BP 114 EP 120 DI 10.1007/BF00288712 PG 7 WC Microbiology SC Microbiology GA LP783 UT WOS:A1993LP78300006 PM 8379810 ER PT J AU PARVEEN, T NAVARROROMAN, L MEDEIROS, LJ RAFFELD, M JAFFE, ES AF PARVEEN, T NAVARROROMAN, L MEDEIROS, LJ RAFFELD, M JAFFE, ES TI LOW-GRADE B-CELL LYMPHOMA OF MUCOSA-ASSOCIATED LYMPHOID-TISSUE ARISING IN THE KIDNEY SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID MALIGNANT-LYMPHOMA; FEATURES; MALT AB We describe a malignant lymphoma arising in the kidney that exhibited clinical and histologic features of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). Clinically, the neoplasm involved the kidney and one perirenal lymph node (stage IIE) and did not recur or disseminate following nephrectomy, lymphadenectomy, and local radiation therapy. Histologically, the neoplasm recapitulated the features of low-grade B-cell lymphomas of MALT at other sites. The neoplastic cells resembled centrocyte-like cells, some of which formed lymphoepithelial lesions with renal tubules, and reactive lymphoid follicles were scattered within the neoplasm. The neoplastic cells expressed monotypic cytoplasmic Igkappa. Low-grade B-cell MALT lymphomas arising in the kidney are rare. Their occurrence further demonstrates the diversity of anatomical sites that may be involved by MALT lymphomas. In addition, this neoplasm also had histologic and cytologic features resembling those of monocytoid B-cell lymphoma, supporting the hypothesis that low-grade B-cell lymphomas of MALT and monocytoid B-cell lymphomas are closely related and may be two morphological manifestations of the same neoplasm. C1 NCI,PATHOL LAB,HEMATOPATHOL SECT,BLDG 10,ROOM 2N202,BETHESDA,MD 20892. UNIV FLORIDA,SCH MED,DEPT PATHOL,GAINESVILLE,FL 32611. RHODE ISL HOSP,DEPT PATHOL,PROVIDENCE,RI 02902. NR 18 TC 58 Z9 58 U1 0 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD AUG PY 1993 VL 117 IS 8 BP 780 EP 783 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA LR011 UT WOS:A1993LR01100003 PM 8135916 ER PT J AU SHAHAR, E FOLSOM, AR WU, KK DENNIS, BH SHIMAKAWA, T CONLAN, MG DAVIS, CE WILLIAMS, OD AF SHAHAR, E FOLSOM, AR WU, KK DENNIS, BH SHIMAKAWA, T CONLAN, MG DAVIS, CE WILLIAMS, OD TI ASSOCIATIONS OF FISH INTAKE AND DIETARY N-3 POLYUNSATURATED FATTY-ACIDS WITH A HYPOCOAGULABLE PROFILE - THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY SO ARTERIOSCLEROSIS AND THROMBOSIS LA English DT Article DE BLOOD COAGULATION FACTORS; FIBRINOGEN; FACTOR-VIII; VON-WILLEBRAND FACTOR; PROTEIN-C ID CORONARY HEART-DISEASE; COD-LIVER OIL; VII COAGULANT ACTIVITY; PLASMA-FIBRINOGEN; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; HEMOSTATIC FUNCTION; PROTEIN-C; DOCOSAHEXAENOIC ACIDS; SERUM-CHOLESTEROL AB Recent epidemiological evidence indicates that the hemostatic profile is an important predictor of cardiovascular disease, yet its dietary determinants are not well established. An important question is whether dietary fatty acid intake influences blood levels of coagulation proteins. We examined potential dietary determinants of six hemostatic factors - fibrinogen, factor VII, factor VIII, von Willebrand factor (vWF), protein C, and antithrombin III-in four population-based samples totaling over 15000 participants, blacks and whites, in the Atherosclerosis Risk in Communities (ARIC) Study. Usual dietary intake was assessed by a food frequency questionnaire. Cross-sectional associations were explored using multiple linear regression analysis, adjusting for gender, race, age, body mass index, smoking status, alcohol use, diabetes, and field center. Dietary intake of n-3 polyunsaturated fatty acids (PUFAs) showed negative associations with fibrinogen, factor VIII, and vWF (blacks and whites) and a positive association with protein C (whites only). Fish intake, the major source of dietary n-3 PUFAs, was similarly related to the hemostatic profile: a 1 serving per day greater fish intake was associated with the following predicted differences (95% confidence interval): fibrinogen, -2.9 mg/dL (-6.3, 0.5); factor VIII, -3.3% (-5.4, -1.3); vWF, -2.7% (-5.2, -0.1) (blacks and whites); and protein C, +0.07 mug/mL (0.03, 0.11) (whites only). Other nutrients or foods were variably associated with the hemostatic factors. These population-based associations, although cross-sectional, suggest that increases in n-3 PUFA intake from fish may modify the blood levels of several coagulation factors. C1 UNIV TEXAS,SCH MED,DIV HEMATOL ONCOL,HOUSTON,TX 77025. UNIV N CAROLINA,COLLABORAT STUDIES COORDINATING CTR,CHAPEL HILL,NC 27514. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV ALABAMA,SCH PUBL HLTH,BIRMINGHAM,AL 35294. RP SHAHAR, E (reprint author), UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,SUITE 300,1300 S 2ND ST,MINNEAPOLIS,MN 55454, USA. RI Wu, Kenneth Kun-Yu/B-1070-2010 FU NHLBI NIH HHS [N01-HC-55015, N01-HC-55018, N01-HC-55016] NR 68 TC 88 Z9 88 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1049-8834 J9 ARTERIOSCLER THROMB JI Arterioscler. Thromb. PD AUG PY 1993 VL 13 IS 8 BP 1205 EP 1212 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA LQ684 UT WOS:A1993LQ68400009 PM 8343495 ER PT J AU JACOBSSON, LTH KNOWLER, WC PILLEMER, S HANSON, RL PETTITT, DJ NELSON, RG DELPUENTE, A MCCANCE, DR CHARLES, MA BENNETT, PH AF JACOBSSON, LTH KNOWLER, WC PILLEMER, S HANSON, RL PETTITT, DJ NELSON, RG DELPUENTE, A MCCANCE, DR CHARLES, MA BENNETT, PH TI RHEUMATOID-ARTHRITIS AND MORTALITY - A LONGITUDINAL-STUDY IN PIMA-INDIANS SO ARTHRITIS AND RHEUMATISM LA English DT Article ID CORONARY HEART-DISEASE; DIABETES-MELLITUS; HIGH PREVALENCE; FOLLOW-UP; DEATH; SURVIVAL; PROTEINURIA; POPULATION; PROGNOSIS; ROCHESTER AB Objective. To determine the effect of rheumatoid arthritis (RA) on mortality rates. Methods. Longitudinal analyses of data from a cohort of Pima Indians from the Gila River Indian Community in Arizona, who were followed up during the period February 1965 through December 1989. Results. Among 2,979 study subjects aged greater-than-or-equal-to 25 years, there were 858 deaths, 79 of which occurred in subjects with RA (36 men, 43 women). Age- and sex-adjusted mortality rates were slightly higher in subjects with RA than in those without (mortality rate ratio 1.28, 95% confidence interval [95% CI] 1.01-1.62). Among those with RA, mortality rates were higher in older subjects (mortality rate ratio 1.51 per 10-year increase in age, 95% CI 1.22-1.88), in male subjects (mortality rate ratio 2.23, 95% CI 1.44-3.45, adjusted for age), and in subjects with proteinuria (mortality rate ratio 1.88, 95% CI 1.02-3.46, adjusted for age and sex). Mortality rate ratios for these risk factors were similar in subjects without RA. In addition, among subjects with RA, rheumatoid factor (RF) positivity was predictive of death (mortality rate ratio 1.94, 95% CI 1.10-3.43), and the excess mortality was found primarily among subjects who were seropositive. The death rate from cardiovascular disease (mortality rate ratio 1.77, 95% CI 1.10-2.84) and from liver cirrhosis or other alcohol-related disease (mortality rate ratio 2.52, 95% CI 1.06-6.01) was increased in persons with RA. Conclusion. The results of this population-based study suggest that although the risk of mortality in subjects with RA is significantly higher than in those without RA, the risk ratio is in the lower range of that described previously in studies of clinic-based cohorts. RF positivity as a predictor of early death among subjects with RA indicates that the immunologic processes in seropositive RA may contribute to the events that eventually lead to early death. C1 NATL INST ARTHRITIS & MUSCULOSKETETAL & SKIN DIS,BETHESDA,MD. CLEVELAND CLIN FDN,DEPT BIOSTAT & EPIDEMIOL,PHOENIX,MD. UNIV NAPLES,DEPT RHEUMATOL,I-80138 NAPLES,ITALY. NATL INST DIABET & DIGEST & KIDNEY DIS,DIABETES & ARTHRITIS EPIDEMIOL SECT,PHOENIX,AZ. NATL INST ARTHRITIS & MUSCULOSKELETAL & SKIN DIS,PHOENIX,AZ. RI Nelson, Robert/B-1470-2012; Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 38 TC 133 Z9 140 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 AUG PY 1993 VL 36 IS 8 BP 1045 EP 1053 DI 10.1002/art.1780360804 PG 9 WC Rheumatology SC Rheumatology GA LR486 UT WOS:A1993LR48600003 PM 8343181 ER PT J AU HAXBY, JV PARASURAMAN, R LALONDE, F ABBOUD, H AF HAXBY, JV PARASURAMAN, R LALONDE, F ABBOUD, H TI SUPERLAB - GENERAL-PURPOSE MACINTOSH SOFTWARE FOR HUMAN EXPERIMENTAL-PSYCHOLOGY AND PSYCHOLOGICAL-TESTING SO BEHAVIOR RESEARCH METHODS INSTRUMENTS & COMPUTERS LA English DT Article AB SuperLab is a general-purpose psychology testing package for the Macintosh. SuperLab presents static visual and auditory stimuli in blocks of trials, each trial consisting of a user-specified sequence of stimuli. Responses can be recorded from the keyboard or from switches connected to an I/O board Stimuli can be contingent on subjects' responses, allowing feedback based on response accuracy. Timing uses Time Manager routines from the Macintosh Toolbox. Data are recorded in a text format with tabs delimiting fields, allowing analysis and presentation by other Macintosh spreadsheet, statistics, and graph-making applications. SuperLab has a Macintosh user interface for developing experiments. Psychological tasks can also be designed and modified with any application that generates a text format file. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. CATHOLIC UNIV AMER,WASHINGTON,DC 20064. CEDRUS CORP,WHEATON,MD. RP HAXBY, JV (reprint author), NIA,NEUROSCI LAB,BLDG 10,ROOM 6C414,BETHESDA,MD 20892, USA. NR 2 TC 53 Z9 53 U1 0 U2 1 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 SN 0743-3808 J9 BEHAV RES METH INSTR JI Behav. Res. Methods Instr. Comput. PD AUG PY 1993 VL 25 IS 3 BP 400 EP 405 DI 10.3758/BF03204531 PG 6 WC Psychology, Mathematical; Psychology, Experimental SC Psychology GA LP974 UT WOS:A1993LP97400008 ER PT J AU FONTANA, D POST, RM WEISS, SRB PERT, A AF FONTANA, D POST, RM WEISS, SRB PERT, A TI THE ROLE OF D1 AND D2 DOPAMINE-RECEPTORS IN THE ACQUISITION AND EXPRESSION OF COCAINE-INDUCED CONDITIONED INCREASES IN LOCOMOTOR BEHAVIOR SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE COCAINE; CONDITIONING; D1 AND D2 AGONISTS; D1 AND D2 ANTAGONISTS; LOCOMOTOR ACTIVITY; RAT ID PIMOZIDE BLOCKS ESTABLISHMENT; D-2 AGONIST QUINPIROLE; NUCLEUS-ACCUMBENS; STEREOTYPED BEHAVIOR; D-AMPHETAMINE; SENSITIZATION; RATS; HALOPERIDOL; ANTAGONISTS; DRUGS AB Certain motoric effects of cocaine increase in intensity with repetitive administration. Conditioned drug effects are among the primary determinants of such sensitization. The purpose of these experiments was to evaluate the role of D1 and D2 dopamine (DA) receptor mechanisms in the acquisition and expression of cocaine conditioning. On Day 1, rats were injected with cocaine (40 mg/kg) either before (PAIRED) or after (UNPAIRED) exposure to a locomotor activity chamber. On Day 2, all animals were injected with a low dose of cocaine (10 mg/kg) prior to placement in the locomotor chambers. Conditioning on Day 2 was evidenced by significantly higher activity levels in the PAIRED group relative to the UNPAIRED or saline-treated groups. Pretreatment with D1 (SCH 23390) or D2 (raclopride, sulpiride, haloperidol) DA antagonists on Day 1 prevented the development of conditioning as assessed on Day 2, indicating that both receptor subtypes are involved in acquisition. However, pretreatment with raclopride or SCH 23390 on Day 2, prior to cocaine injections, did not eliminate the differences in behavior between the conditioned and non-conditioned groups. Neither D1 (SKF 82958, SK.F 38393) nor D2 (quinpirole) agonists administered alone were effective in establishing conditioning, while a combination of SKF 82958 and quinpirole was effective, suggesting that conditioning in this experimental paradigm requires the concurrent activation of both receptor subtypes. In the final study it was found that conditioned cocaine effects could be revealed only in the presence of quinpirole or apomorphine on Day 2. The D1 agonists (SKF 38393 and SKF 82958) were ineffective. This would suggest either that only quinpirole and apomorphine are effective in amplifying the conditioned effects of cocaine on Day 2 or that the cues produced by these drugs are more similar to those produced by cocaine than those produced by D1 agonists. C1 NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 75 TC 50 Z9 50 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD AUG PY 1993 VL 4 IS 4 BP 375 EP 387 PG 13 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA LU465 UT WOS:A1993LU46500010 ER PT J AU FLAMMANG, AM GELBOIN, HV AOYAMA, T GONZALEZ, FJ MCCOY, GD AF FLAMMANG, AM GELBOIN, HV AOYAMA, T GONZALEZ, FJ MCCOY, GD TI N-NITROSOPYRROLIDINE METABOLISM BY CDNA-EXPRESSED HUMAN CYTOCHROME-P-450S SO BIOCHEMICAL ARCHIVES LA English DT Article ID CHRONIC ETHANOL-CONSUMPTION; HUMAN LIVER-MICROSOMES; DIRECTED EXPRESSION; SEQUENCE; ACTIVATION; NITROSAMINES; GENE; RAT; TOBACCO; N'-NITROSONORNICOTINE AB A cDNA-directed expression of human P-450 isoforms in cultured human hepatoma cells was used to determine the role of individual P-450 isoforms in metabolism of NPYR. The purpose of these studies was to determine the contribution of specific human cytochrome P450 isoforms to the alpha-hydroxylation of NPYR. Of the preparations tested, isoforms 2E1 and 2A6 exhibited the highest rates of NPYR metabolism while marginal levels of activity were observed with isoforms 1A2, 2B6, 2C8, 2C9, 3A3, 3A4, 3A5, and noninfected HepG2 cells. No activity was detected with isoform 2D6. Kinetic analysis of the 2E1 lysate demonstrated an apparent K(m) of 0.034 mM and a V(max) of 27.2 pmol/min/mg protein, while analysis of the 2A6 lysate demonstrated an apparent K(m) of 1.26 mM and a V(max) of 15.0 pmol/min/mg protein. P-450 2E1 was the preferred isoform at low substrate concentrations while P-450 2A6 was active at higher substrate concentrations. Since both P-450s 2A6 and 2E1 metabolize N-nitrosamines, the presence of either of these two isoforms in tissues should be indicative of sensitivity to nitrosamine carcinogenesis. C1 NIH,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RP FLAMMANG, AM (reprint author), CASE WESTERN RESERVE UNIV,SCH MED,DEPT ENVIRONM HLTH SCI,CLEVELAND,OH 44106, USA. NR 35 TC 19 Z9 19 U1 0 U2 0 PU MBR PRESS INC PI KENYON PA PO BOX P, KENYON, MN 55946-000P SN 0749-5331 J9 BIOCHEM ARCH JI Biochem. Arch. PD AUG PY 1993 VL 9 IS 3 BP 197 EP 204 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LT769 UT WOS:A1993LT76900001 ER PT J AU GRUBB, MF KASOFSKY, J STRONG, J ANDERSON, LW CYSYK, RL AF GRUBB, MF KASOFSKY, J STRONG, J ANDERSON, LW CYSYK, RL TI SERUM STIMULATION OF UDP-GLUCOSE DEHYDROGENASE-ACTIVITY IN SWISS 3T3 FIBROBLASTS SO BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL LA English DT Article ID CELLS; ACID RP GRUBB, MF (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892, USA. NR 13 TC 7 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS AUST PI MARRICKVILLE PA LOCKED BAG 16, MARRICKVILLE NSW 2204, AUSTRALIA SN 1039-9712 J9 BIOCHEM MOL BIOL INT JI Biochem. Mol. Biol. Int. PD AUG PY 1993 VL 30 IS 5 BP 819 EP 827 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LV672 UT WOS:A1993LV67200003 PM 8220234 ER PT J AU LANDSMAN, D BUSTIN, M AF LANDSMAN, D BUSTIN, M TI A SIGNATURE FOR THE HMG-1 BOX DNA-BINDING PROTEINS SO BIOESSAYS LA English DT Review ID MOBILITY GROUP PROTEIN-1; SEX-DETERMINING REGION; TRANSCRIPTION FACTOR; CHROMOSOMAL-PROTEINS; YEAST MITOCHONDRIA; ALPHA-ENHANCER; FACTOR-I; GENE; SEQUENCE; SRY AB A diverse group of DNA-binding regulatory proteins share a common structural domain which is homologous to the sequence of a highly conserved and abundant chromosomal protein, HMG-1. Proteins containing this HMG-1 box regulate various cellular functions involving DNA binding, suggesting that the target DNA sequences share a common structural element. Members of this protein family exhibit a dual DNA-binding specificity: each recognizes a unique sequence as well as a common DNA conformation. The highly conserved HMG-1/-2 proteins may modulate the binding of other HMG-1 box proteins to bent DNA. We examine the structural and functional relationships between the proteins, identify their signature and describe common features of their target DNA elements. C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RP LANDSMAN, D (reprint author), NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BLDG 38A,ROOM 8N-807,BETHESDA,MD 20894, USA. RI Landsman, David/C-5923-2009; Bustin, Michael/G-6155-2015; OI Landsman, David/0000-0002-9819-6675 NR 67 TC 226 Z9 229 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0265-9247 J9 BIOESSAYS JI Bioessays PD AUG PY 1993 VL 15 IS 8 BP 539 EP 546 DI 10.1002/bies.950150807 PG 8 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA LU748 UT WOS:A1993LU74800006 PM 8135767 ER PT J AU MORI, C WELCH, JE FULCHER, KD OBRIEN, DA EDDY, EM AF MORI, C WELCH, JE FULCHER, KD OBRIEN, DA EDDY, EM TI UNIQUE HEXOKINASE MESSENGER-RIBONUCLEIC-ACID LACKING THE PORIN-BINDING DOMAIN ARE DEVELOPMENTALLY EXPRESSED IN MOUSE SPERMATOGENIC CELLS SO BIOLOGY OF REPRODUCTION LA English DT Article ID MORPHOLOGICAL CHARACTERIZATION; NUCLEOTIDE-SEQUENCE; GLUCOKINASE GENE; CLONED CDNA; RAT-LIVER; TESTIS; CLONING; KINASE; INSITU; DNA AB We have identified cDNAs representing three hexokinase mRNAs (Hk1-sa, Hk1-sb, Hk1-sc) by screening mouse spermatogenic cell cDNA libraries with a mouse hepatoma cell line hexokinase (Hk1) cDNA [Arora KY, Fanciulli M, Pederson PL. J Biol Chem 1990; 265:6481-6488]. Although all three cDNAs show 99% identity to the somatic Hk1 cDNA sequence throughout most of their coding region, they differ from this sequence at the 5' end. They contain a common spermatogenic cell-specific sequence and a sequence unique to each cDNA immediately 5' to the common domain. However, they lack the porin-binding domain (PBD) present in this region of Hk1, used for binding to a pore-forming protein in the outer mitochondrial membrane. These observations appear to support a model proposed by others for hexokinase gene evolution in mammals. In addition, we found that Hk1-sb has an internal sequence that is not present in Hk1, Hk1-sa, or Hk1-sc. Moreover, Hk1-sa and Hk1-sb transcripts are developmentally expressed in mouse spermatogenic cells. Hk1-sa mRNA is first expressed during meiosis and continues to be present in postmeiotic germ cells, while the more abundant Hk1-sb mRNA is detected only in postmeiotic germ cells. These and other findings suggest that enzymes encoded by Hk1-sa, Hk1-sb, and Hk1-sc are present only in spermatogenic cells. C1 NIEHS,LRDT,GAMETE BIOL SECT,POB 1233,C4-01,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,REPROD BIOL LABS,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT PEDIAT,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT CELL BIOL & ANAT,CHAPEL HILL,NC 27599. FU NICHD NIH HHS [R01 HD026485, HD-26485, P30-HD-18968] NR 51 TC 72 Z9 73 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD AUG PY 1993 VL 49 IS 2 BP 191 EP 203 DI 10.1095/biolreprod49.2.191 PG 13 WC Reproductive Biology SC Reproductive Biology GA MA651 UT WOS:A1993MA65100001 PM 8396993 ER PT J AU CHOONGKITTAWORN, NM KIM, KH DANNER, DB GRISWOLD, MD AF CHOONGKITTAWORN, NM KIM, KH DANNER, DB GRISWOLD, MD TI EXPRESSION OF PROHIBITIN IN RAT SEMINIFEROUS EPITHELIUM SO BIOLOGY OF REPRODUCTION LA English DT Article ID RECEPTOR MESSENGER-RNA; SERTOLI CELLS; SPERMATOGENIC CELLS; GENE; SEQUENCE; MOUSE; CDNA; IDENTIFICATION; TUBULES; TESTIS AB Subtractive hybridization was used to isolate cDNAs highly expressed in stages IX-XI of the cycle of the seminiferous epithelium in the rat. One of the cloned cDNAs was sequenced and shown to be homologous to a previously described cDNA encoding mt prohibitin. Northern blot analyses showed that 1.9- and 1.2-kb transcripts were present in Sertoli cells whereas 1.5-, 1.2-, and 0.7-kb transcripts were expressed in germ cells. Western blot analyses with anti-peptide antibody to prohibitin revealed only a single 30-kDa protein in testis. Immunocytochemistry demonstrated that prohibitin protein was expressed constitutively in adult Leydig cells and Sertoli cells at all stages. Immunoreactivity of prohibitin was very low in preleptotene spermatocytes, very high in leptotene spermatocytes, and very low in zygotene spermatocytes. In pachytene spermatocytes, immunoreactivity was very high in stages VII-XI and was minimal during stages XII and XIV. No protein was detected in spermatogonia and spermatocytes undergoing mitotic and meiotic divisions, respectively. These studies show that the prohibitin gene is expressed differentially in testis. The expression pattern of the prohibitin gene in rat testis appears to correlate with a proposed anti-proliferative role of probibitin. C1 WASHINGTON STATE UNIV,DEPT BIOCHEM & BIOPHYS,PULLMAN,WA 99164. WASHINGTON STATE UNIV,DEPT GENET & CELL BIOL,PULLMAN,WA 99164. NIA,MOLEC GENET LAB,BALTIMORE,MD 21224. FU NICHD NIH HHS [HD 25846]; PHS HHS [11H-2940-8751] NR 30 TC 37 Z9 37 U1 1 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD AUG PY 1993 VL 49 IS 2 BP 300 EP 310 DI 10.1095/biolreprod49.2.300 PG 11 WC Reproductive Biology SC Reproductive Biology GA MA651 UT WOS:A1993MA65100014 PM 8373953 ER PT J AU GOLEBIEWSKI, WM BADER, JP CUSHMAN, M AF GOLEBIEWSKI, WM BADER, JP CUSHMAN, M TI DESIGN AND SYNTHESIS OF COSALANE, A NOVEL ANTI-HIV AGENT SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID LYMPHADENOPATHY-ASSOCIATED VIRUS; AURINTRICARBOXYLIC ACID ATA; PLACEBO-CONTROLLED TRIAL; AIDS-RELATED COMPLEX; AZIDOTHYMIDINE AZT; MOLECULAR-WEIGHT; ZIDOVUDINE AZT; DOUBLE-BLIND; INFECTIVITY; TOXICITY AB Cosalane, a novel anti-HIV agent having a dichlorodisalicylmethane unit linked to C-3 of cholestane by a three-carbon linker, was synthesized by a convergent route. C1 PURDUE UNIV,DEPT MED CHEM & PHARMACOGNOSY,W LAFAYETTE,IN 47907. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,ANTIVIRALS EVALUAT BRANCH,BETHESDA,MD 20852. NR 18 TC 28 Z9 28 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD AUG PY 1993 VL 3 IS 8 BP 1739 EP 1742 DI 10.1016/S0960-894X(00)80053-0 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA LW592 UT WOS:A1993LW59200051 ER PT J AU ATWATER, I SHERMAN, A AF ATWATER, I SHERMAN, A TI IMPORTANCE OF ISLET-CELL SYNCHRONY FOR THE BETA-CELL GLUCOSE RESPONSE SO BIOPHYSICAL JOURNAL LA English DT Note ID LANGERHANS C1 NIDDKD,MATH RES BRANCH,BETHESDA,MD 20892. RP ATWATER, I (reprint author), NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892, USA. NR 7 TC 1 Z9 1 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD AUG PY 1993 VL 65 IS 2 BP 565 EP 565 PG 1 WC Biophysics SC Biophysics GA LU233 UT WOS:A1993LU23300003 PM 8218885 ER PT J AU STOKES, CL RINZEL, J AF STOKES, CL RINZEL, J TI DIFFUSION OF EXTRACELLULAR K+ CAN SYNCHRONIZE BURSTING OSCILLATIONS IN A MODEL ISLET OF LANGERHANS SO BIOPHYSICAL JOURNAL LA English DT Article ID PANCREATIC BETA-CELLS; GLUCOSE-INDUCED OSCILLATIONS; SINGLE-MOUSE ISLETS; B-CELLS; POTASSIUM CONCENTRATION; INTRACELLULAR CA-2+; ELECTRICAL-ACTIVITY; CALCIUM CURRENTS; ACCUMULATION; INACTIVATION AB Electrical bursting oscillations of mammalian pancreatic beta-cells are synchronous among cells with in an islet. While electrical coupling among cells via gap junctions has been demonstrated, its extent and topology are unclear. The beta-cells also share an extracellular compartment in which oscillations of K+ concentration have been measured (Perez-Armendariz and Atwater, 1985). These oscillations (1-2 mM) are synchronous with the burst pattern, and apparently are caused by the oscillating voltage-dependent membrane currents: Extracellular K+ concentration (K(e)) rises during the depolarized active (spiking) phase and falls during the hyperpolarized silent phase. Because raising K(e) depolarizes the cell membrane by increasing the potassium reversal potential (VK), any cell in the active phase should recruit nonspiking cells into the active phase. The opposite is predicted for the silent phase. This positive feedback system might couple the cells' electrical activity and synchronize bursting. We have explored this possibility using a theoretical model for bursting of beta-cells (Sherman et al., 1988) and K+ diffusion in the extracellular space of an islet. Computer simulations demonstrate that the bursts synchronize very quickly (within one burst) without gap junctional coupling among the cells. The shape and amplitude of computed K(e) oscillations resemble those seen in experiments for certain parameter ranges. The model cells synchronize with exterior cells leading, though incorporating heterogeneous cell properties can allow interior cells to lead. The model islet can also be forced to oscillate at both faster and slower frequencies using periodic pulses of higher K+ in the medium surrounding the islet. Phase plane analysis was used to understand the synchronization mechanism. The results of our model suggest that diffusion of extracellular K+ may contribute to coupling and synchronization of electrical oscillations in beta-cells within an islet. C1 NIDDKD,MATH RES BRANCH,BETHESDA,MD 20892. NR 56 TC 25 Z9 25 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD AUG PY 1993 VL 65 IS 2 BP 597 EP 607 PG 11 WC Biophysics SC Biophysics GA LU233 UT WOS:A1993LU23300008 PM 8218890 ER PT J AU ROSENBERG, HF AF ROSENBERG, HF TI BACTERIAL CHROMOSOMAL CONTAMINATION OF A EUKARYOTIC CDNA LIBRARY SO BIOTECHNIQUES LA English DT Letter RP ROSENBERG, HF (reprint author), NIAID,HOST DEF LAB,BLDG 10,ROOM 11N113,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 4 TC 2 Z9 2 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 AUG PY 1993 VL 15 IS 2 BP 200 EP 201 PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LQ808 UT WOS:A1993LQ80800001 PM 8104000 ER PT J AU ORLIC, D FISCHER, R NISHIKAWA, SI NIENHUIS, AW BODINE, DM AF ORLIC, D FISCHER, R NISHIKAWA, SI NIENHUIS, AW BODINE, DM TI PURIFICATION AND CHARACTERIZATION OF HETEROGENEOUS PLURIPOTENT HEMATOPOIETIC STEM-CELL POPULATIONS EXPRESSING HIGH-LEVELS OF C-KIT RECEPTOR SO BLOOD LA English DT Article ID COLONY-FORMING CELLS; BONE-MARROW; RHODAMINE-123 FLUORESCENCE; REPOPULATING ABILITY; PROGENITOR CELLS; SI-LOCUS; W-LOCUS; CFU-S; MOUSE; SEPARATION C1 NEW YORK MED COLL,VALHALLA,NY 10595. ARMED FORCES RADIOBIOL RES INST,BETHESDA,MD 20814. KUMAMOTO UNIV,SCH MED,DEPT PATHOL,KUMAMOTO 860,JAPAN. RP ORLIC, D (reprint author), NHLBI,CLIN HEMATOL BRANCH,BLDG 10,ROOM 7C103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 41 TC 169 Z9 172 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 1993 VL 82 IS 3 BP 762 EP 770 PG 9 WC Hematology SC Hematology GA LQ741 UT WOS:A1993LQ74100011 PM 7687891 ER PT J AU AOKI, SK HOLLAND, PV FERNANDO, LP KURAMOTO, IK ANDERSON, S SAZAMA, K SCHOENING, V JOHNSON, P WILBER, JC FENNER, L ALTER, HJ AF AOKI, SK HOLLAND, PV FERNANDO, LP KURAMOTO, IK ANDERSON, S SAZAMA, K SCHOENING, V JOHNSON, P WILBER, JC FENNER, L ALTER, HJ TI EVIDENCE OF HEPATITIS IN PATIENTS RECEIVING TRANSFUSIONS OF BLOOD COMPONENTS CONTAINING ANTIBODY TO HEPATITIS-C SO BLOOD LA English DT Article ID NON-B-HEPATITIS; VIRUS-INFECTION; NON-A; POSTTRANSFUSION HEPATITIS; DONORS; RECIPIENTS; PREVALENCE; RNA C1 SACRAMENTO MED FDN,CTR BLOOD,SACRAMENTO,CA. CTR BLOOD RES,SACRAMENTO,CA. CHIRON CORP,EMERYVILLE,CA. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NR 19 TC 23 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 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 1993 VL 82 IS 3 BP 1000 EP 1005 PG 6 WC Hematology SC Hematology GA LQ741 UT WOS:A1993LQ74100044 PM 7687886 ER PT J AU TOPKA, H VALLSSOLE, J MASSAQUOI, SG HALLETT, M AF TOPKA, H VALLSSOLE, J MASSAQUOI, SG HALLETT, M TI DEFICIT IN CLASSICAL-CONDITIONING IN PATIENTS WITH CEREBELLAR DEGENERATION SO BRAIN LA English DT Article ID NICTITATING-MEMBRANE RESPONSE; INTERPOSITUS NUCLEUS; INFERIOR OLIVE; LESIONS; RABBITS; STIMULATION; CORTEX; REFLEX; DEPRESSION; STIMULUS AB There is evidence from animal experiments that the cerebellum and its associated brainstem circuitry are involved in the acquisition of the conditioned response. In order to obtain evidence for their involvement in humans, we studied classical delay conditioning, using the eyeblink conditioned response, in five patients with pure cerebellar cortical atrophy and seven patients with olivopontocerebellar atrophy. The results were compared with those obtained in a group of neurologically healthy volunteers matched with the patients for age and sex. The two groups of patients had similar abnormalities in the acquisition of the conditioned response and produced fewer conditioned responses than in the control subjects in any given block of trials. Many of the patients' conditioned responses were inappropriately timed with respect to the conditioned stimulus. These results support the role of the cerebellum in the expression and timing of the conditioned response. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BLDG 10,ROOM 5N226,BETHESDA,MD 20892. NR 31 TC 170 Z9 170 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0006-8950 J9 BRAIN JI Brain PD AUG PY 1993 VL 116 BP 961 EP 969 DI 10.1093/brain/116.4.961 PN 4 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA LT179 UT WOS:A1993LT17900013 PM 8353718 ER PT J AU LASA, MSM PODGOR, MJ DATILES, MB CARUSO, RC MAGNO, BV AF LASA, MSM PODGOR, MJ DATILES, MB CARUSO, RC MAGNO, BV TI GLARE SENSITIVITY IN EARLY CATARACTS SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID MEASURING CONTRAST SENSITIVITY; VISUAL-ACUITY; VISION AB In a previous study significant glare sensitivity (using Vistech MCT8000) was found only in patients with posterior subcapsular cataracts (PSC) beyond the very early (LOCS II grade 1) stage. The aim of the present study was to evaluate glare sensitivity in patients with early cataracts. The brightness acuity tester (BAT) was used with the Pelli-Robson chart on 50 patients with early cataracts (LOCS II grade 1 or 2) and on 14 normal volunteers. Only age and PSC were found to be associated with change in contrast sensitivity at high glare. Eyes with grade 1 PSC were not significantly different from eyes with grade 0 PSC after adjusting for age. Eyes with grade 2 PSC had significant glare effect compared with eyes having grade 0 PSC. Thus, glare sensitivity is associated only with early (grade 2) PSC. Other tests still need to be developed to assess visual function changes in patients with early cortical and nuclear cataracts. C1 NEI,BIOMETRY & EPIDEMIOL PROGRAM,OPHTHALM GENET & CLIN SERV BRANCH,BETHESDA,MD 20892. OI Datiles, Manuel III B./0000-0003-4660-1664 NR 21 TC 11 Z9 11 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD AUG PY 1993 VL 77 IS 8 BP 489 EP 491 DI 10.1136/bjo.77.8.489 PG 3 WC Ophthalmology SC Ophthalmology GA LQ253 UT WOS:A1993LQ25300007 PM 8025045 ER PT J AU ABASSI, ZA GOLOMB, E BRIDENBAUGH, R KEISER, HR AF ABASSI, ZA GOLOMB, E BRIDENBAUGH, R KEISER, HR TI METABOLISM OF ENDOTHELIN-1 AND BIG ENDOTHELIN-1 BY RECOMBINANT NEUTRAL ENDOPEPTIDASE EC.3.4.24.11 SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE ENDOTHELIN-1; BIG-ENDOTHELIN-1[1-38]; NEUTRAL ENDOPEPTIDASE INHIBITORS; RECOMBINANT NEUTRAL ENDOPEPTIDASE; SQ-28,603; PHOSPHORAMIDON; HPLC ID MEMBRANE-BOUND METALLOENDOPEPTIDASE; ATRIAL-NATRIURETIC-PEPTIDE; CONVERTING ENZYME; CATHEPSIN-D; 24.11 ENKEPHALINASE; HEART-FAILURE; SQ 28,603; RAT LUNG; CONVERSION; CELLS AB 1 Inhibitors of neutral endopeptidase EC.3.4.24.11 (NEP) have been shown to attenuate the hypertensive effect of big-endothelin-1 (BET-1) in rats. To determine whether NEP converts BET-1 to endothelin-1 (ET-1), the effect of a recombinant NEP (rNEP) on BET-1 and on ET-1 was assessed in vitro. 2 Incubation of [I-125]-ET-1 with 1 mug ml-1 of rNEP resulted in degradation of the peptide within minutes. Increase in the amount of rNEP to 10 mug ml-1 led to total cleavage of [I-125]-ET-1 within seconds. 3 Phosphoramidon (10 muM) or SQ-28,603 (100 muM) totally suppressed the degradation of [I-125]-ET-1 by rNEP. 4 The degradation of [I-125]-BET-1 by either 1 or 10 mug ml-1 of rNEP was much slower than that of [I-125]-ET-1. Again, both phosphoramidon and SQ 28,603 protected the peptide from degradation. 5 Intact [I-125]-ET-1 was not observed when [I-125]-BET-1 was incubated with rNEP. 6 These data show that neutral endopeptidase EC.3.4.24.11 is not an endothelin convertin enzyme. C1 GENENTECH INC,S SAN FRANCISCO,CA 94080. RP ABASSI, ZA (reprint author), NHLBI,HYPERTENS ENDOCRINE BRANCH,BLDG 10,ROOM 8C103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 37 TC 37 Z9 38 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD AUG PY 1993 VL 109 IS 4 BP 1024 EP 1028 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LN917 UT WOS:A1993LN91700023 PM 8401914 ER PT J AU VARGO, MM GERBER, LH AF VARGO, MM GERBER, LH TI EXERCISE STRATEGIES FOR OSTEOPOROSIS SO BULLETIN ON THE RHEUMATIC DISEASES LA English DT Article ID BONE-MINERAL CONTENT; POSTMENOPAUSAL WOMEN; PHYSICAL-ACTIVITY; DENSITY RP VARGO, MM (reprint author), NIH,DEPT REHABIL MED,BETHESDA,MD 20892, USA. NR 18 TC 3 Z9 3 U1 0 U2 0 PU ARTHRITIS FOUNDATION PI ATLANTA PA 1314 SPRING STREET NW, ATLANTA, GA 30309 SN 0007-5248 J9 B RHEUM DIS JI Bull. Rheum. Dis. PD AUG PY 1993 VL 42 IS 5 BP 6 EP 9 PG 4 WC Rheumatology SC Rheumatology GA LW438 UT WOS:A1993LW43800003 PM 8242162 ER PT J AU HALLETT, M AF HALLETT, M TI PHYSIOLOGY OF BASAL GANGLIA DISORDERS - AN OVERVIEW SO CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES LA English DT Article ID SOMATOSENSORY EVOKED-POTENTIALS; POSITRON EMISSION TOMOGRAPHY; LA-TOURETTES SYNDROME; RECIPROCAL INHIBITION; PARKINSONS-DISEASE; SPASMODIC DYSPHONIA; MOVEMENT-DISORDERS; WRITERS CRAMP; HAND CRAMPS; DYSTONIA AB The pathophysiology of the movement disorders arising from basal ganglia disorders has been uncertain, in part because of a lack of a good theory of how the basal ganglia contribute to normal voluntary movement. An hypothesis for basal ganglia function is proposed here based on recent advances in anatomy and physiology. Briefly, the model proposes that the purpose of the basal ganglia circuits is to select and inhibit specific motor synergies to carry out a desired action. The direct pathway is to select and the indirect pathway is to inhibit these synergies. The clinical and physiological features of Parkinson's disease, L-DOPA dyskinesias, Huntington's disease, dystonia and tic are reviewed. An explanation of these features is put forward based upon the model. RP HALLETT, M (reprint author), NINCDS,MED NEUROL BRANCH,BLDG 10,ROOM 5N226,BETHESDA,MD 20892, USA. NR 43 TC 149 Z9 151 U1 0 U2 10 PU CANADIAN J NEUROL SCI INC PI CALGARY PA PO BOX 4220, STATION C EDITORIAL & SUBSCRIPTION SERV, CALGARY AB T2T 5N1, CANADA SN 0317-1671 J9 CAN J NEUROL SCI JI Can. J. Neurol. Sci. PD AUG PY 1993 VL 20 IS 3 BP 177 EP 183 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA LV339 UT WOS:A1993LV33900001 PM 8221380 ER PT J AU GREM, JL MCATEE, N BALIS, F MURPHY, R VENZON, D KRAMER, B GOLDSPIEL, B BEGLEY, M ALLEGRA, CJ AF GREM, JL MCATEE, N BALIS, F MURPHY, R VENZON, D KRAMER, B GOLDSPIEL, B BEGLEY, M ALLEGRA, CJ TI A PHASE-II STUDY OF CONTINUOUS-INFUSION 5-FLUOROURACIL AND LEUCOVORIN WITH WEEKLY CISPLATIN IN METASTATIC COLORECTAL-CARCINOMA SO CANCER LA English DT Article DE 5-FLUOROURACIL; COLORECTAL CANCER; BIOCHEMICAL MODULATION; PHARMACOKINETICS ID ATLANTIC ONCOLOGY PROGRAM; VENOUS INFUSION; PHARMACOKINETICS; FLUOROURACIL; COMBINATION; CANCER; TRIAL; ACID; 5-FU AB Background. Prolonged infusional 5-fluorouracil (5-FU) and bolus 5-FU modulated by leucovorin are associated with higher response rates than bolus 5-FU alone. Cisplatin enhances 5-FU cytotoxicity in some preclinical models. Methods. The authors tested the feasibility of combining concurrent infusional leucovorin (500 mg/m2/d) with protracted infusional 5-FU (200 mg/m2/d) and weekly bolus cisplatin (20 mg/m2) in 22 patients with metastatic colorectal cancer. Results. Four partial responses (PR) were noticed among 21 evaluable patients (19%). The median time to treatment failure and median survival were 6 months and 11 months, respectively. All but two patients required 5-FU dose reduction after a median of 2 weeks because of mucositis. However, severe mucositis and diarrhea occurred in only 18% and 5% of the patients, respectively. Palmar-plantar erythrodysesthesia of mild to moderate severity occurred in 55% of patients. Megaloblastic changes were evident in the peripheral blood during therapy, and may reflect prolonged DNA-directed toxicity of 5-FU. The median tolerated dose level of 5-FU was 113 mg/m2/d (range, 64-150 mg/m2/d). Mean steady-state plasma concentrations (Cp(ss)) of 5-FU appeared to increase linearly from 0.19 muM to 0.39 muM over the dose range 64 to 200 mg/m2/d. Patients with grade 2 gastrointestinal toxicity had significantly higher 5-FU Cp(ss) than patients with grade 0 or 1 toxicity. Conclusions. The early onset of toxicity with this regimen of protracted infusional 5-FU/high-dose leucovorin and weekly cisplatin required marked attenuation of the 5-FU dose intensity, and the results were no better than that expected with infusional 5-FU alone. C1 NIH,CTR CLIN,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NCI,CLIN ONCOL PROGRAM,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT PHARM,BETHESDA,MD 20892. NCI,PEDIAT ONCOL BRANCH,BETHESDA,MD 20892. RP GREM, JL (reprint author), NCI,NAVY MED ONCOL BRANCH,NATL NAVAL MED CTR,BLDG 8,ROOM 5101,BETHESDA,MD 20892, USA. RI Venzon, David/B-3078-2008 NR 22 TC 24 Z9 24 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD AUG 1 PY 1993 VL 72 IS 3 BP 663 EP 668 DI 10.1002/1097-0142(19930801)72:3<663::AID-CNCR2820720307>3.0.CO;2-V PG 6 WC Oncology SC Oncology GA LP720 UT WOS:A1993LP72000005 PM 8334622 ER PT J AU GRAHAM, SJ SHARPE, RW STEINBERG, SM COTELINGAM, JD SAUSVILLE, EA FOSS, FM AF GRAHAM, SJ SHARPE, RW STEINBERG, SM COTELINGAM, JD SAUSVILLE, EA FOSS, FM TI PROGNOSTIC IMPLICATIONS OF A BONE-MARROW HISTOPATHOLOGIC CLASSIFICATION-SYSTEM IN MYCOSIS-FUNGOIDES AND THE SEZARY-SYNDROME SO CANCER LA English DT Article DE MYCOSIS FUNGOIDES; SEZARY SYNDROME; LYMPHOMA; BONE MARROW BIOPSY; PROGNOSIS; EOSINOPHILIA; LYMPHOID AGGREGATES ID T-CELL LYMPHOMA; TRANSFORMATION AB Background. The authors devised a histopathologic classification system for interpreting bone marrow biopsy materials in patients with mycosis fungoides and the Sezary syndrome and correlated histopathologic findings with clinical stage and outcome. Methods. Bone marrow specimens from 90 consecutively staged patients were examined for lymphoid infiltrates, benign or cytologically atypical lymphoid aggregates, and large or cytologically transformed cells. Results. Thirty-seven (41%) marrows were involved, two with diffuse lymphomatous infiltrates and 35 with lymphoid aggregates. Twelve of the 35 had lymphoid aggregates consisting of cytologically normal-appearing lymphocytes, and 23 had aggregates composed of cytologically atypical lymphocytes. Eleven patients had greater than 5% large cytologically transformed cells. Patients with infiltrative disease or cytologically atypical aggregates had an inferior survival compared with those with cytologically normal lymphocytes (P2 = 0.0042), and patients with aggregates consisting of cytologically normal lymphocytes had a survival comparable with that of patients with uninvolved marrows (P2 = 0.33). Whereas most patients with cytologically atypical marrows had advanced skin and lymph node involvement, 28% had early skin stage. Bone marrow eosinophilia was noticed in 38% of patients and was not consistently associated with peripheral blood eosinophilia or clinical stage. Conclusions. These results suggest that patients with cytologically atypical lymphoid aggregates or diffuse lymphomatous infiltration of the marrow have an inferior survival regardless of clinical stage, whereas those with lymphoid aggregates consisting of cytologically normal-appearing lymphocytes have a survival indistinguishable from that of patients without lymphoid aggregates. C1 NAVAL HOSP BETHESDA,NCI,BETHESDA,MD. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. NR 22 TC 12 Z9 12 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD AUG 1 PY 1993 VL 72 IS 3 BP 726 EP 734 DI 10.1002/1097-0142(19930801)72:3<726::AID-CNCR2820720316>3.0.CO;2-P PG 9 WC Oncology SC Oncology GA LP720 UT WOS:A1993LP72000014 PM 8334625 ER PT J AU SWANSON, GM RAGHEB, NE LIN, CS HANKEY, BF MILLER, B HORNROSS, P WHITE, E LIFF, JM HARLAN, LC MCWHORTER, WP MULLAN, PB KEY, CR AF SWANSON, GM RAGHEB, NE LIN, CS HANKEY, BF MILLER, B HORNROSS, P WHITE, E LIFF, JM HARLAN, LC MCWHORTER, WP MULLAN, PB KEY, CR TI BREAST-CANCER AMONG BLACK-AND-WHITE WOMEN IN THE 1980S - CHANGING PATTERNS IN THE UNITED-STATES BY RACE, AGE, AND EXTENT OF DISEASE SO CANCER LA English DT Article DE BREAST CANCER; INCIDENCE; RACE; TRENDS; SCREENING ID RISING INCIDENCE; MAMMOGRAPHY AB Background. This national study of breast cancer incidence and mortality was conducted to determine whether patterns of change differ for black and white women, to evaluate patterns by extent of disease, and to determine whether recent patterns of breast cancer are consistent with results that one would expect due to increases in use of screening examinations by women. Methods. The study included 104,351 cases of in situ or invasive breast cancer diagnosed between 1983 and 1989 among women from the nine geographic areas participating in the National Cancer Institute Surveillance, Epidemiology, and End Results program. Breast cancer incidence patterns were examined by extent of disease for black and white women and by age at diagnosis. Results. Significant increases occurred in the incidence of all early-stage breast cancers. Concomitantly, significant decreases occurred in the incidence of the most advanced-stage breast cancers. Although both white and black women experienced significant increases in early-stage breast cancer, black women have substantially lower rates of the least extensive breast cancers. Conclusion. These results strongly suggest that a major explanation for the increase in breast cancer incidence in the 1980s may well be the increased prevalence of breast cancer screening among women in the United States. They also suggest a consistent benefit of screening across all age groups from 40 to 49 years through 70 years and older. C1 NO CALIF CANC CTR,UNION CITY,CA. NCI,DIV CANC PREVENT & CONTROL,APPL RES BRANCH,SURVEILLANCE PROGRAM,ROCKVILLE,MD. MICHIGAN STATE UNIV,COLL HUMAN MED,E LANSING,MI 48824. FRED HUTCHINSON CANC RES CTR,CANC PREVENT PROGRAM,SEATTLE,WA 98104. EMORY UNIV,SCH PUBL HLTH,DIV EPIDEMIOL,ATLANTA,GA 30322. UNIV UTAH,SCH MED,DIV HEMATOL ONCOL,SALT LAKE CITY,UT 84112. UNIV NEW MEXICO,SCH MED,DEPT PATHOL,ALBUQUERQUE,NM 87131. NCI,CANC STAT BRANCH,ROCKVILLE,MD. RP SWANSON, GM (reprint author), MICHIGAN STATE UNIV,CTR CANC,A-128 E FEE HALL,E LANSING,MI 48824, USA. FU NCI NIH HHS [N01-CN-05225] NR 22 TC 48 Z9 48 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD AUG 1 PY 1993 VL 72 IS 3 BP 788 EP 798 DI 10.1002/1097-0142(19930801)72:3<788::AID-CNCR2820720326>3.0.CO;2-C PG 11 WC Oncology SC Oncology GA LP720 UT WOS:A1993LP72000024 PM 8334632 ER PT J AU MULSHINE, JL JETT, M CUTTITTA, F TRESTON, AM QUINN, K SCOTT, F IWAI, N AVIS, I LINNOILA, RI SHAW, GL AF MULSHINE, JL JETT, M CUTTITTA, F TRESTON, AM QUINN, K SCOTT, F IWAI, N AVIS, I LINNOILA, RI SHAW, GL TI SCIENTIFIC BASIS FOR CANCER PREVENTION - INTERMEDIATE CANCER MARKERS SO CANCER LA English DT Article; Proceedings Paper CT NATIONAL CONF ON CANCER PREVENTION AND EARLY DETECTION CY SEP 10-12, 1992 CL CHICAGO, IL SP AMER CANC SOC DE INTERMEDIATE END POINT MARKER; BIOMARKER PROMOTION BIOLOGY; EPITHELIUM; GASTRIN-RELEASING PEPTIDE ID HUMAN-LUNG-CANCER; CHEMOPREVENTIVE AGENTS; CARCINOMA; GROWTH; DIFFERENTIATION; CARCINOGENESIS; RETINOIDS; CELLS AB Promising cancer clinical trials results involving the disruption of early stages of cancer with intervention agents such as tamoxifen or retinoids have led to significant new research interest in developing preventative strategy for the control of epithelial cancers. Key to the efficient progress in this field is a clear understanding of the complex biology of the early stages of cancerization that proceed on the epithelial surface. Systematic analysis of the biology of strategic targets such as growth factors is one approach to this problem. Gastrin-releasing peptide is an autocrine growth factor for certain types of lung cancer cells. Mechanisms involved in the production and activation of this peptide are discussed as an example of how rational approaches to neutralization of cancer promotion biology can be achieved. The tools to monitor the success of this type of intervention also emerge from the understanding of the biology of growth factors, and intermediate end point markers that determine the presence or effects of a growth factor are attractive candidates for evaluation. Additional biologic tools reflecting the early stages of the cancer process need to be validated for use in serially evaluating the status of the relevant epithelium so that the ongoing success of a cancer intervention procedure can be established. Through this type of translational research, important applications of molecular biology may greatly improve the success of preventative strategies for cancer control. RP MULSHINE, JL (reprint author), NCI,DIV CANC PREVENT & CONTROL,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD 20850, USA. NR 44 TC 12 Z9 14 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD AUG 1 PY 1993 VL 72 IS 3 SU S BP 978 EP 983 DI 10.1002/1097-0142(19930801)72:3+<978::AID-CNCR2820721305>3.0.CO;2-T PG 6 WC Oncology SC Oncology GA LQ618 UT WOS:A1993LQ61800004 PM 8334673 ER PT J AU EPPS, RP MANLEY, MW AF EPPS, RP MANLEY, MW TI PREVENTION OF TOBACCO USE DURING CHILDHOOD AND ADOLESCENCE - 5 STEPS TO PREVENT THE ONSET OF SMOKING SO CANCER LA English DT Article; Proceedings Paper CT NATIONAL CONF ON CANCER PREVENTION AND EARLY DETECTION CY SEP 10-12, 1992 CL CHICAGO, IL SP AMER CANC SOC DE SMOKING; SMOKING PREVENTION; ADOLESCENCE; CHILDHOOD AND ADOLESCENT TOBACCO USE PREVENTION ID SMOKELESS TOBACCO; CHILDREN AB Background. Most tobacco users become addicted during childhood and adolescence. To reduce the prevalence of tobacco-related illnesses, more emphasis must be placed on preventing the onset of tobacco use. Physicians can play a major role. Methods. Based on a series of clinical trials, the National Cancer Institute (NCI) developed recommendations to help patients stop smoking. Behavioral and developmental research have identified factors that contribute to the onset of smoking. The American Academy of Pediatrics (AAP) has developed guidelines for health supervision from birth to adulthood, including engaging parents and children as partners in health care. The NCI recommendations, behavioral research results, and AAP guidelines were integrated to develop a strategy to prevent the onset of tobacco use. Results. The NCI proposes five steps to prevent tobacco use during childhood and adolescence. There are five physician activities, beginning with the letter A, including anticipatory guidance, ask, advise, assist, and arrange follow-up. Anticipatory guidance, the practice of counseling for potential problems, is a key part of health care for the young. The nature of these steps varies, depending on the child's age, developmental stage, and behavior, as well as smoking habits of family members. Conclusion. Despite the long-term consequences of smoking, onset and addiction to tobacco use usually begins in childhood. Therefore, physicians who care for children have a major role in eliminating tobacco use by preventing its onset. RP EPPS, RP (reprint author), NCI,APPLICAT PREVENT & EARLY DETECT SECT,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 19 TC 10 Z9 11 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD AUG 1 PY 1993 VL 72 IS 3 SU S BP 1002 EP 1004 DI 10.1002/1097-0142(19930801)72:3+<1002::AID-CNCR2820721309>3.0.CO;2-G PG 3 WC Oncology SC Oncology GA LQ618 UT WOS:A1993LQ61800008 PM 8334651 ER PT J AU HEIMENDINGER, J AF HEIMENDINGER, J TI COMMUNITY NUTRITION INTERVENTION STRATEGIES FOR CANCER RISK REDUCTION SO CANCER LA English DT Article; Proceedings Paper CT NATIONAL CONF ON CANCER PREVENTION AND EARLY DETECTION CY SEP 10-12, 1992 CL CHICAGO, IL SP AMER CANC SOC DE INTERVENTION; NUTRITION; RISK REDUCTION; CANCER ID PROJECT; DISEASE AB As the accumulated evidence continues to indicate a need for Americans to modify current eating patterns and other lifestyle factors to reduce the risk of chronic diseases, the demand for community nutrition interventions will accelerate. All interventions require certain basic elements, such as measurable objectives and robust evaluation designs. However, there are other overarching strategies whose application will contribute to the research knowledge base for community interventions. This article focuses on three such strategies: use of the national health objectives, use of community channels, and development of interventions based on theories of health behavior. The application of these strategies to the National 5 A Day for Better Health Program is illustrated. RP HEIMENDINGER, J (reprint author), NCI,DIV CANC PREVENT & CONTROL,9000 ROCKVILLE PIKE,EPN 330,BETHESDA,MD 20892, USA. NR 13 TC 12 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 0008-543X J9 CANCER JI Cancer PD AUG 1 PY 1993 VL 72 IS 3 SU S BP 1019 EP 1023 DI 10.1002/1097-0142(19930801)72:3+<1019::AID-CNCR2820721313>3.0.CO;2-B PG 5 WC Oncology SC Oncology GA LQ618 UT WOS:A1993LQ61800012 PM 8334653 ER PT J AU LEVY, W MEADOWS, BS QUINTKASNER, S CARROLL, R GORRELL, CR AF LEVY, W MEADOWS, BS QUINTKASNER, S CARROLL, R GORRELL, CR TI CHEMOTHERAPY AGENTS .1. SO CANCER NURSING LA English DT Article C1 NCI,BETHESDA,MD 20892. RP LEVY, W (reprint author), NIH,DEPT CLIN CTR NURSING,BETHESDA,MD 20892, USA. NR 13 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 AUG PY 1993 VL 16 IS 4 BP 321 EP 336 PG 16 WC Oncology; Nursing SC Oncology; Nursing GA LV412 UT WOS:A1993LV41200009 PM 8402608 ER PT J AU NOMIZU, M YAMAMURA, K KLEINMAN, HK YAMADA, Y AF NOMIZU, M YAMAMURA, K KLEINMAN, HK YAMADA, Y TI MULTIMERIC FORMS OF TYR-ILE-GLY-SER-ARG (YIGSR) PEPTIDE ENHANCE THE INHIBITION OF TUMOR-GROWTH AND METASTASIS SO CANCER RESEARCH LA English DT Note ID SYNTHETIC PEPTIDE; CELL-ADHESION; LAMININ; IDENTIFICATION; GLYCOPROTEIN; INVASION; BINDING AB The Tyr-Ile-Gly-Ser-Arg (YIGSR) peptide derived from the laminin B1 chain has been shown to decrease tumor growth and metastasis. Utilizing the multimeric antigen peptide system assembled on a branched lysine core, we synthesized several sizes of multimeric YIGSR, (CH3CO-Tyr-Ile-Gly-Ser-Arg-Gly)16-Lys8-Lys4-Lys2-Lys-Gly [(Ac-YIGSRG)16 K8K4K2KG] (designated Ac-Y16), (Ac-YIGSRG)8K4K2KG (Ac-Y8), and (Ac-YIGSRG)4K2KG (Ac-Y4), and related peptides, Ac-(YIGSRG)4-NH2 (Ac-Y4L) and Ac-YIGSR-NH2 (Ac-Y1) and evaluated their biological activities in inhibiting tumor growth and metastasis. Coinjection of 0.2 mg/mouse of Ac-Y16 i.v. with B16-F10 mouse melanoma cells inhibited lung colony formation by 97%, whereas 0.2 mg/mouse of Ac-Y1 inhibited by 50%. The larger the peptide (Ac-Y16 > Ac-Y8 > Ac-Y4 > Ac-Y1), the more inhibitory effect there was on lung metastasis. Ac-Y16 also inhibited the growth of s.c.-injected B16-F10 tumors. These data demonstrate that the multimeric YIGSR peptides strongly enhanced the activity of YIGSR in inhibiting tumor growth and metastasis and suggest that these compounds are potentially useful for clinical applications. RP NOMIZU, M (reprint author), NIDR,DEV BIOL LAB,BLDG 30,ROOM 427,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 24 TC 59 Z9 60 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 1993 VL 53 IS 15 BP 3459 EP 3461 PG 3 WC Oncology SC Oncology GA LP641 UT WOS:A1993LP64100003 PM 8339246 ER PT J AU HOLDER, JW ELMORE, E BARRETT, JC AF HOLDER, JW ELMORE, E BARRETT, JC TI GAP JUNCTION FUNCTION AND CANCER SO CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE-C; INTER-CELLULAR COMMUNICATION; LIVER-TUMOR PROMOTERS; EARLY MOUSE EMBRYOS; INTERCELLULAR COMMUNICATION; RAT-LIVER; METABOLIC COOPERATION; MEDIATED INHIBITION; EPITHELIAL-CELLS; EPIDERMAL-CELLS AB Gap junctions (GJs) provide cell-to-cell communication of essential metabolites and ions. GJs allow tissues to average responses, clear waste products, and minimize the effects of xenobiotics by dilution and allowing steady-state catabolism. Many chemicals can adversely affect the membrane GJ assembly causing reversible alterations in GJ intercellular communication. During toxicity essential metabolites, ions, and regulators are not shared homeostatically throughout a tissue community. Alterations in metabolic circuits are thought to interrupt organ integration. Persistent GJ perturbation can cause chronic effects (e.g., cancer), and many tumor promoters inhibit GJ intercellular communication. Liver precancerous foci intracommunicate (but at a reduced level) and intercommunicate improperly (or not at all) across the foci boundary to normal cells. In time, foci can become less regulated and more isolated within the tissue. Gjs remain reduced quantitatively in the tumor progression stage and may be qualitatively altered in metastasis since connections are made between the primary tumor cells and foreign host cells at the secondary metastatic site. Cell sorting and binding mechanisms by the cell adhesion molecules and integrins may also be altered at secondary sites. This may allow the relocation of primary tumor cells and nurturance via GJs at the secondary site. C1 NATL INST ADV INVITRO SCI,IRVINE,CA 92715. NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. RP HOLDER, JW (reprint author), US EPA,OFF RES & DEV RD689,OFF HLTH ENVIRONM ASSESSMENT,WASHINGTON,DC 20460, USA. NR 149 TC 199 Z9 213 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 AUG 1 PY 1993 VL 53 IS 15 BP 3475 EP 3485 PG 11 WC Oncology SC Oncology GA LP641 UT WOS:A1993LP64100008 PM 8393376 ER PT J AU SHIELDS, PG BOWMAN, ED HARRINGTON, AM DOAN, VT WESTON, A AF SHIELDS, PG BOWMAN, ED HARRINGTON, AM DOAN, VT WESTON, A TI POLYCYCLIC AROMATIC HYDROCARBON-DNA ADDUCTS IN HUMAN LUNG AND CANCER SUSCEPTIBILITY GENES SO CANCER RESEARCH LA English DT Article ID WHITE BLOOD-CELLS; DIOL-EPOXIDE-DNA; SISTER CHROMATID EXCHANGE; CIGARETTE-SMOKING; HUMAN-PLACENTA; P-32-POSTLABELING ANALYSIS; CYTOCHROME-P450IA1 GENE; CARCINOGEN METABOLISM; MONOCLONAL-ANTIBODIES; ENHANCED SENSITIVITY AB Molecular dosimetry for polycyclic aromatic hydrocarbon-DNA adducts, genetic predisposition to cancer, and their interrelationships are under study in numerous laboratories. This report describes a modified P-32-postlabeling assay for the detection of polycyclic aromatic hydrocarbon-DNA adducts that uses immunoaffinity chromatography to enhance chemical specificity and quantitative reliability. The assay incorporates internal standards to determine direct molar ratios of adducts to unmodified nucleotides and to assess T4 polynucleotide kinase labeling efficiency. High performance liquid chromatography is used to assure adequacy of DNA enzymatic digestion. The assay was validated using radiolabeled benzo(a)pyrene-diol-epoxide modified DNA (r = 0.76. P < 0.05) thereby assessing all variables from enzymatic digestion to detection. Thirty-eight human lung samples were examined and adducts were detected in seven. A subset of samples also was examined for benzo(a)pyrene-diol-epoxide-DNA adducts by immunoaffinity chromatography, high performance liquid chromatography, and synchronous fluorescence spectroscopy. A high correlation between the two assays was found (P = 0.006). The lung samples were then analyzed by the polymerase chain reaction for the presence of mutations in the cytochrome P-450 (CYP) 1A1 and glutathione S-transferase mu (GSTmu) genes. A positive association was identified for adduct levels and GSTmu null genotypes (P = 0.038). No correlation was found between polycyclic aromatic hydrocarbon-adduct levels and CYP1A1 exon 7 mutations. Age, race, and serum cotinine were not related to adduct levels. Multivariate analysis indicated that only the GSTmu genotype was associated with polycyclic aromatic hydrocarbon-DNA adduct levels. This work demonstrates that the P-32-postlabeling assay can be modified for chemically specific adduct detection and that it can be used in the assessment of potentially important genetic factors for cancer risk. The absence of a functional GSTmu gene in humans is likely one such factor. RP SHIELDS, PG (reprint author), NCI,DIV CANC ETIOL,HUMAN CARCINOGENESIS LAB,BLDG 37,ROOM 2C16,BETHESDA,MD 20892, USA. RI Shields, Peter/I-1644-2012 NR 65 TC 204 Z9 210 U1 2 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 1993 VL 53 IS 15 BP 3486 EP 3492 PG 7 WC Oncology SC Oncology GA LP641 UT WOS:A1993LP64100009 PM 8339251 ER PT J AU REDDY, BS RAO, CV RIVENSON, A KELLOFF, G AF REDDY, BS RAO, CV RIVENSON, A KELLOFF, G TI CHEMOPREVENTION OF COLON CARCINOGENESIS BY ORGANOSULFUR COMPOUNDS SO CANCER RESEARCH LA English DT Article ID MALE F344 RATS; DIALLYL SULFIDE; 5-(2-PYRAZINYL)-4-METHYL-1,2-DITHIOL-3-THIONE OLTIPRAZ; INTESTINAL CARCINOGENESIS; DIETARY-FAT; INHIBITION; CANCER; AZOXYMETHANE; METABOLISM; DITHIOLTHIONES AB It has been reported that several naturally occurring and related synthetic organosulfur compounds exert chemopreventive effects in several target organs in rodent models. The chemopreventive actions of 40 and 80% maximum tolerated doses (MTD) of organosulfur compounds, namely anethole trithione, diallyl disulfide, N-acetylcysteine, and taurine, administered in AIN-76A diet, on azoxymethane (AOM)-induced neoplasia were investigated in male F344 rats. Also, the effects of these agents on the activities of phase II enzymes, namely glutathione S-transferase (GST), NAD(P)H-dependent quinone reductase, and UDP-glucuronosyl transferase, in the liver and colonic mucosa and tumors were assessed. The MTD levels of anethole trithione, diallyl disulfide, N-acetylcysteine, and taurine were determined in male F344 rats and found to be 250, 250, 1500, and 1500 ppm, respectively. At 5 weeks of age, animals were fed the control diet (AIN-76A) or experimental diets containing 40 or 80% MTD levels of each test agent. All animals in each group, except those allotted for vehicle (saline) treatment, were administered AOM s.c. at a dose rate of 15 mg/kg body weight once weekly for 2 weeks. All animals were necropsied during week 52 after the second AOM injection. Colonic mucosal and tumor and liver enzyme activities were measured in animals fed 80% MTD levels of each test agent. Colon tumors were subjected to histopathological evaluation and classified as invasive or noninvasive adenocarcinomas. Colon tumor incidence (percentage of animals with tumors) and tumor multiplicity (tumors/animal) were compared among various dietary groups. The results indicated that administration of 200 ppm (80% MTD) anethole trithione significantly inhibited the incidence and multiplicity of both invasive and noninvasive adenocarcinomas, whereas feeding of 100 ppm (40% MTD) anethole trithione or 100 (40% MTD) or 200 ppm (80% MTD) diallyl disulfide suppressed only invasive adenocarcinomas of the colon. Although diets containing N-acetylcysteine and taurine inhibited colon tumor multiplicity, the effect was somewhat marginal. GST, NAD-(P)H-dependent quinone reductase, and UDP-glucuronosyl transferase activities in colonic mucosa and tumor and liver were significantly elevated in animals fed anethole trithione or diallyl disulfide, compared to those fed the control diet. N-Acetylcysteine and taurine slightly but significantly increased only the GST activity in the liver. Although other mechanisms are not excluded, inhibition of AOM-induced colon carcinogenesis by anethole trithione and diallyl disulfide may be associated, in part, with increased activities of phase II enzymes such as GST, NAD(P)H-dependent quinone reductase, and UDP-glucuronosyl transferase in the liver and colon. C1 AMER HLTH FDN,DIV PATHOL & TOXICOL,VALHALLA,NY 10595. NCI,DIV CANC CONTROL & PREVENT,CHEMOPREVENT BRANCH,BETHESDA,MD 20892. RP REDDY, BS (reprint author), AMER HLTH FDN,DIV NUTR CARCINOGENESIS,1 DANA RD,VALHALLA,NY 10595, USA. RI Chinthalapally, Rao/B-3633-2010 FU NCI NIH HHS [CA-17613, N01-CN-85095-05] NR 46 TC 190 Z9 195 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 1993 VL 53 IS 15 BP 3493 EP 3498 PG 6 WC Oncology SC Oncology GA LP641 UT WOS:A1993LP64100010 PM 8339252 ER PT J AU OGASAWARA, M ROSENBERG, SA AF OGASAWARA, M ROSENBERG, SA TI ENHANCED EXPRESSION OF HLA MOLECULES AND STIMULATION OF AUTOLOGOUS HUMAN TUMOR-INFILTRATING LYMPHOCYTES FOLLOWING TRANSDUCTION OF MELANOMA-CELLS WITH GAMMA-INTERFERON GENES SO CANCER RESEARCH LA English DT Article ID NECROSIS-FACTOR-ALPHA; IFN-GAMMA; T-CELLS; CLASS-I; MONOCLONAL-ANTIBODY; ADVANCED CANCER; MURINE TUMOR; INTERLEUKIN-2; ANTIGENS; IMMUNOTHERAPY AB Gene therapy for cancer is being tested in clinical trials using tumor-infiltrating lymphocytes (TIL) or tumor cells modified by the insertion of genes coding for interleukin 2 or tumor necrosis factor alpha. In the present study, we investigated the feasibility of transducing human tumor cells with genes coding for gamma-interferon (IFNgamma) or alpha-interferon (IFNalpha), which are two other cytokines that can enhance host antitumor immune responses. Tumor cells from 12 melanoma and 2 renal cell carcinoma patients were transduced with retroviral vectors containing the gene for IFNgamma. Northern blot analysis showed IFN-gamma transcripts only in the IFNgamma gene-transduced cells. In both IFNgamma-secreting and non-secreting tumor lines, the cell surface expression of HLA class I and class II molecules increased following transduction. However, the magnitude of the increase in HLA expression appeared to be greater in tumor lines secreting IFN-gamma. Two melanoma cell lines were successfully transduced with an IFNalpha retroviral vector. Melanoma cells transduced with the IFNalpha gene contained IFNalpha RNA transcripts and secreted large amounts of IFNalpha. In contrast to cells transduced with the IFN-gamma gene, the expression of HLA class II molecules was not increased in the IFNalpha gene-transduced cells. Finally, we tested the ability of HLA.DR+ melanoma cells, which had been transduced with the IFN-gamma gene, to stimulate specific cytokine release by autologous CD4+ TIL. Specific secretion of cytokine by TIL occurred when the TIL and IFNgamma gene-transduced tumor cells were cultured together but not when TIL were cultured alone or with control nontransduced tumor cells. These results suggest that molecules newly expressed on the transduced cells promoted antigen presentation and T-cell responses against the transduced tumor cells. The insertion of the IFNgamma gene into melanoma cells may be useful either for active immunization against melanoma or for the generation of TIL to be used in adoptive immunotherapy. RP OGASAWARA, M (reprint author), NCI,SURG BRANCH,BETHESDA,MD 20892, USA. NR 49 TC 64 Z9 64 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 AUG 1 PY 1993 VL 53 IS 15 BP 3561 EP 3568 PG 8 WC Oncology SC Oncology GA LP641 UT WOS:A1993LP64100022 PM 8101762 ER PT J AU REDDY, BS RAO, CV RIVENSON, A KELLOFF, G AF REDDY, BS RAO, CV RIVENSON, A KELLOFF, G TI INHIBITORY EFFECT OF ASPIRIN ON AZOXYMETHANE-INDUCED COLON CARCINOGENESIS IN F344 RATS SO CARCINOGENESIS LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PROSTAGLANDIN SYNTHESIS INHIBITORS; LARGE-BOWEL CANCER; INTESTINAL CARCINOGENESIS; CHEMOPREVENTIVE AGENTS; COLORECTAL-CANCER; DIETARY-FAT; INDOMETHACIN; PIROXICAM; TUMORS AB Epidemiologic studies suggest that sustained use of aspirin may reduce the risk of development of and mortality due to colon cancer. Previous preclinical studies have shown that several non-steroidal anti-inflammatory drugs act as potential chemopreventive agents in experimentally induced colon cancer models. The present study was designed to investigate the chemopreventive effect of 40 and 80% maximum tolerated dose (MTD) levels of aspirin administered in the diet on azoxymethane (AOM)-induced colon carcinogenesis in male F344 rats. The MTD of aspirin as determined in male F344 rats was 500 p.p.m. Beginning at 5 weeks of age, all animals were randomly divided into various experimental groups (48 rats/group) and fed one of the semipurified diets containing 0, 200 p.p.m. (40% MTD), or 400 ppm (80% MTD) of aspirin. Two weeks later, all animals (36 rats/group) except the vehicle-treated groups (12 rats/group) were administered s.c. injections of AOM at a dose level of 15 mg/kg body wt, once weekly for 2 weeks. All animals were continued on their respective dietary regimen for additional 52 weeks and necropsied. Histopathologic evaluation of colon tumors was performed by routine procedures. Basal levels and ex vivo production of colonic mucosal and tumor prostaglandin E2 (PGE2) were measured in all groups. The results indicate that daily oral administration of 200 and 400 p.p.m. aspirin significantly inhibited the incidence (% animals with tumors) and multiplicity (tumors/animal) of invasive adenocarcinomas of the colon as well as the size of adenocarcinomas. Colonic mucosal and tumor PGE2 levels (basal and ex vivo production) were significantly reduced in animals administered 200 and 400 p.p.m. aspirin. The results of this study support the epidemiologic evidence that ingestion of aspirin inhibits colon carcinogenesis. Although the precise mechanisms of aspirin-induced colon tumor inhibition remain to be determined, it is likely that the effect may be mediated through the modulation of prostaglandin synthesis. C1 AMER HLTH FDN,DIV PATHOL & TOXICOL,VALHALLA,NY 10595. NCI,DIV CANC CONTROL & PREVENT,CHEMOPREVENT BRANCH,BETHESDA,MD 20856. RP REDDY, BS (reprint author), AMER HLTH FDN,DIV NUTR CARCINOGENESIS,VALHALLA,NY 10595, USA. RI Chinthalapally, Rao/B-3633-2010 FU NCI NIH HHS [CN 85095-05, CA 17613] NR 50 TC 317 Z9 324 U1 0 U2 5 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 AUG PY 1993 VL 14 IS 8 BP 1493 EP 1497 DI 10.1093/carcin/14.8.1493 PG 5 WC Oncology SC Oncology GA LT119 UT WOS:A1993LT11900001 PM 8353834 ER PT J AU SUN, Y COLBURN, NH OBERLEY, LW AF SUN, Y COLBURN, NH OBERLEY, LW TI DEPRESSION OF CATALASE GENE-EXPRESSION AFTER IMMORTALIZATION AND TRANSFORMATION OF MOUSE-LIVER CELLS SO CARCINOGENESIS LA English DT Article ID SUPEROXIDE-DISMUTASE; DNA METHYLATION; TUMOR-CELLS; LINES; DIFFERENTIATION; TOXICITY AB To understand the molecular basis of the remarkable decrease of catalase activity after immortalization and malignant transformation of mouse liver cells, expression of the catalase gene was studied in in vivo mouse liver cells and nontransformed normal mouse liver cell line as well as liver cell lines transformed by N-methyl-N-nitro-N-nitrosoguanidine, SV40 virus or by conventional subcultivation. In vivo liver cells had much greater levels of catalase mRNA and immunoreactive protein than in vitro cell lines, which correlates with elevated enzyme activity. Among the cell lines, normal cells had in general higher mRNA levels and more catalase protein than that of the transformed cell tines, also correlating with enzyme activity. The down regulation of catalase gene expression seen in transformed lines may occur transcriptionally rather than posttranscriptionally as demonstrated by cycloheximide and/or actinomycin D treatment. The striking difference in catalase gene expression seen between liver tissue and liver cell lines was unlikely due to gross structural alterations in the catalase gene, but might be explained by a remarkable difference in methylation status of the catalase gene, as demonstrated by Southern blot analysis following HpaII digestion. Our results suggested that during cellular immortalization and malignant transformation, a change in the oxidant stress ultimately led to a cellular response that, in turn, led to down regulation of the catalase gene. C1 UNIV IOWA,RADIAT RES LAB,IOWA CITY,IA 52242. RP SUN, Y (reprint author), NCI,FREDERICK CANC RES CTR,VIRAL CARCINOGENESIS LAB,CELL BIOL SECT,FREDERICK,MD, USA. FU NCI NIH HHS [CA 41267] NR 32 TC 49 Z9 51 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 1993 VL 14 IS 8 BP 1505 EP 1510 DI 10.1093/carcin/14.8.1505 PG 6 WC Oncology SC Oncology GA LT119 UT WOS:A1993LT11900003 PM 8353835 ER PT J AU BEEBE, LE KIM, YE AMIN, S RIGGS, CW KOVATCH, RM ANDERSON, LM AF BEEBE, LE KIM, YE AMIN, S RIGGS, CW KOVATCH, RM ANDERSON, LM TI COMPARISON OF TRANSPLACENTAL AND NEONATAL INITIATION OF MOUSE LUNG AND LIVER-TUMORS BY N-NITROSODIMETHYLAMINE (NDMA) AND 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE (NNK) AND PROMOTABILITY BY A POLYCHLORINATED-BIPHENYLS MIXTURE (AROCLOR 1254) SO CARCINOGENESIS LA English DT Article ID MICE; CONGENERS; BLOOD; EXPOSURE; TISSUE; SERUM AB We have previously shown a positive tumor-promoting effect of a single dose of Aroclor 1254 on lung and liver tumors initiated neonatally in the mouse by N-nitrosodimethylamine (NDMA). In this study, we have confirmed and extended this observation with NDMA and the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) given either transplacentally or postnatally, followed by a single dose of Aroclor 1254 on day 56. This polychlorinated biphenyl (PCB) mixture was an effective promoter of both lung and liver tumors; however, there were specific initiator and sex-related differences in this response. Aroclor administration significantly increased the incidence of lung tumors initiated transplacentally by NDMA or NNK in male mice. Neither nitrosamine initiated tumors transplacentally in females, but lung tumors initiated with NNK and liver tumors caused by NDMA in neonatal females were promoted by PCBs. Both liver and lung tumors initiated neonatally by NDMA in male animals, but not NNK-initiated tumors, were promoted by PCBs. These data confirm that PCBs are able to promote both NDMA- and NNK-initiated tumors, but with chemical-, sex- and age-dependent difference; this suggests influences of both quantitative and qualitative factors in susceptibility to tumor promotion. C1 AMER HLTH FDN,NAYLOR DANA INST DIS PREVENT,VALHALLA,NY 10595. DATA MANAGEMENT SERV INC,FREDERICK,MD 21701. PATHOL ASSOCIATES INC,FREDERICK,MD 21701. RP BEEBE, LE (reprint author), FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. NR 21 TC 33 Z9 34 U1 2 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 1993 VL 14 IS 8 BP 1545 EP 1548 DI 10.1093/carcin/14.8.1545 PG 4 WC Oncology SC Oncology GA LT119 UT WOS:A1993LT11900009 PM 8353839 ER PT J AU STEVNSNER, T MAY, A PETERSEN, LN LARMINAT, F PIRSEL, M BOHR, VA AF STEVNSNER, T MAY, A PETERSEN, LN LARMINAT, F PIRSEL, M BOHR, VA TI REPAIR OF RIBOSOMAL-RNA GENES IN HAMSTER-CELLS AFTER UV IRRADIATION, OR TREATMENT WITH CISPATIN OR ALKYLATING-AGENTS SO CARCINOGENESIS LA English DT Article ID MATRIX ASSOCIATED DNA; NUCLEAR MATRIX; PYRIMIDINE DIMERS; COMPLEMENTATION; TRANSCRIPTION; DAMAGE; LEVEL AB We have measured the DNA damage formation and repair in the ribosomal and the dihydrofolate reductase (DHFR) genes after treatment of hamster cells with different types of DNA damaging agents. In mammalian cells, the ribosomal DNA (rDNA) is transcribed by RNA polymerase I, whereas the DHFR is transcribed by RNA polymerase II. Cells were treated with agents that induce different types of lesions, and that are known to be repaired via different pathways. We used UV (254 nm) irradiation, treatment with cisplatin and treatment with the alkylating agents nitrogen mustard (HN2) and methyl methanesulphonate (MMS). UV induced pyrimidine dimers were detected with the enzyme T4 endonuclease V, which creates nicks at the dimer sites; the breaks are then resolved and identified by denaturing electrophoresis and Southern blot. Intrastrand adducts formed by the alkylating agents HN2 and MMS were quantitated by generating strand breaks at abasic sites after neutral depurination. Interstrand crosslinks (ICL) formed by HN2 and cisplatin were detected by a denaturation-reannealing reaction before neutral agarose gel-electrophoresis. We find that the repair of the pyrimidine dimers is significantly less efficient in the RNA polymerase I transcribed rDNA genes than in RNA polymerase II transcribed DHFR gene at 8 and 24 h after irradiation. ICL and intrastrand adducts induced by HN2 are also removed more slowly from the rDNA than from the DHFR gene. In contrast, MMS induced intrastrand adducts and cisplatin induced ICL are repaired equally efficiently in the RNA polymerase I and RNA polymerase II transcribed genes. We conclude that for some types of DNA damage, there is less repair in the ribosomal genes than in the DHFR; but for other DNA lesions there is no difference. The difference in repair efficiency between the rDNA and the DHFR genes may reflect the different RNA polymerases involved in their transcription. It may, however, alternatively, reflect the different nuclear localization of these genes. C1 NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. SLOVAK ACAD SCI,CANC RES INST,CS-80936 BRATISLAVA,CZECHOSLOVAKIA. RI Pirsel, Miroslav/A-9996-2008 NR 30 TC 22 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 AUG PY 1993 VL 14 IS 8 BP 1591 EP 1596 DI 10.1093/carcin/14.8.1591 PG 6 WC Oncology SC Oncology GA LT119 UT WOS:A1993LT11900017 PM 8353843 ER PT J AU CHEN, B LIU, L CASTONGUAY, A MARONPOT, RR ANDERSON, MW YOU, M AF CHEN, B LIU, L CASTONGUAY, A MARONPOT, RR ANDERSON, MW YOU, M TI DOSE-DEPENDENT RAS MUTATION SPECTRA IN N-NITROSODIETHYLAMINE INDUCED MOUSE-LIVER TUMORS AND 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE INDUCED MOUSE LUNG-TUMORS SO CARCINOGENESIS LA English DT Article ID POLYMERASE CHAIN-REACTION; TOBACCO-SPECIFIC CARCINOGEN; CONFORMATION POLYMORPHISM ANALYSIS; B6C3F1 MICE; CHEMICAL CARCINOGENESIS; ACTIVATED ONCOGENES; CONTINUOUS EXPOSURE; RODENT CARCINOGENS; DNA ALKYLATION; RATS AB In a previous study, the spectrum of H-ras mutations detected in B6C3F1 mouse liver tumors induced by 5, 50 or 150 Amol/kg body wt of N-nitrosodiethylamine (NDEA) was similar to that in spontaneous B6C3F1 mouse liver tumors, suggesting that activation of the H-ras gene in NDEA-induced mouse liver tumors may not be the direct result of the chemical interaction with the H-ras gene. In the present study, mutations in the H-ras oncogene from B6C3F1 mouse liver tumors induced by 5 or 50 mumol/kg body wt of NDEA were characterized by DNA amplification with polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP) and direct sequence analysis. Twenty-one of 66 NDEA-induced B6C3F1 mouse liver tumors contained activated H-ras gene with 2 of 21 having a CG to AT transversion at the first base of codon 61, 17 of 21 having AT to GC transition and 2 of 21 having an AT to TA transversion at the second base of codon 61 in the H-ras gene. The predominant mutation, AT to GC transition (17/21, 81%) is consistent with the formation of O4-ethylthymine adduct, and is distinct from the predominant CG to AT transversion (50%) at the first base of codon 61 detected in H-ras gene from NDEA-induced B6C3F1 mouse fiver tumors in a previous study by Stowers et al. Mutations in the K-ras oncogene from 59 A/J mouse lung tumors induced by 0.53 mmol/kg body wt of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were also characterized by using the above mentioned methods. Forty-six of 59 NNK-induced A/J mouse lung tumors contained activated K-ras genes. All 46 (100%) of the activated K-ras gene had GC to AT transitions at the second base of codon 12. The same mutation was observed in 70% (7/10) of the K-ras oncogene from A/J lung tumors induced by 4.8 mmol/kg body wt (given in 21 doses) of NNK. These data suggest that other factors in addition to genotoxic effect might be involved in the induction of rodent tumors by some carcinogens when given at higher doses. Therefore, further studies to compare the dose-dependent differences in the profile of ras mutations induced by chemical carcinogens may help to assess human cancer risk. Mutation(s) in exons 5-8 of the p53 gene was not found in these NDEA-induced mouse liver tumors and NNK-induced mouse lung tumors. C1 UNIV LAVAL,SCH PHARM,CANC ETIOL & CHEMOPREVENT LAB,QUEBEC CITY G1K 7P4,QUEBEC,CANADA. NIEHS,RES TRIANGLE PK,NC 27709. FU NCI NIH HHS [CA58554] NR 44 TC 77 Z9 77 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 AUG PY 1993 VL 14 IS 8 BP 1603 EP 1608 DI 10.1093/carcin/14.8.1603 PG 6 WC Oncology SC Oncology GA LT119 UT WOS:A1993LT11900019 PM 8353844 ER PT J AU BELL, DA TAYLOR, JA BUTLER, MA STEPHENS, EA WIEST, J BRUBAKER, LH KADLUBAR, FF LUCIER, GW AF BELL, DA TAYLOR, JA BUTLER, MA STEPHENS, EA WIEST, J BRUBAKER, LH KADLUBAR, FF LUCIER, GW TI GENOTYPE-PHENOTYPE DISCORDANCE FOR HUMAN ARYLAMINE N-ACETYLTRANSFERASE (NAT2) REVEALS A NEW SLOW-ACETYLATOR ALLELE COMMON IN AFRICAN-AMERICANS SO CARCINOGENESIS LA English DT Note ID BLADDER-CANCER; CATALYTIC MECHANISM; CARCINOGENESIS; INVOLVEMENT AB Carcinogenic arylamines are acetylated by the hepatic N-acetyltransferase. This enzyme is polymorphic in humans and in some epidemiological studies, the slow-acetylator phenotype has been associated with higher risk of bladder cancer and tower risk of colorectal cancer. The presence of two germline copies of any of several mutant alleles of the NAT2 gene produces a slow-acetylation phenotype. We used a PCR-RFLP technique to identify three known slow-acetylator alleles (M1, M2 and M3). Comparison of results from PCR-RFLP genotyping with caffeine metabolism phenotyping in 42 individuals suggested that an additional slow-acetylator allele was present in our sampled population. We sequenced the NAT2 gene for several discordant slow-acetylator individuals and found a G > A base-change in codon 64 that caused a Arg > Glu amino acid substitution. This sequence change, termed the 'M4' allele, was found in all of the discordant individuals in our population and apparently causes a slow-acetylation phenotype. In addition, we have determined that NAT2 allele frequencies in 372 Caucasian-Americans (WT = 0.25, M1 = 0.45, M2 = 0.28, M3 = 0.02, and M4 = 0.00) and in 128 African-Americans (WT = 0.36, M1 = 0.30, M2 = 0.22, M3 = 0.02 and M4 = 0.09) are significantly different (P < 0.0001). The M4 allele was not found in 372 unrelated Caucasians and appears to be of African origin. C1 NIEHS,BIOCHEM RISK ANAL LAB,C3-03,POB 12333,RES TRIANGLE PK,NC 27709. NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. NIEHS,MOLEC TOXICOL BRANCH,RES TRIANGLE PK,NC 27709. MED COLL GEORGIA,AUGUSTA,GA 30912. NATL CTR TOXICOL RES,JEFFERSON,AR. OI taylor, jack/0000-0001-5303-6398 NR 23 TC 312 Z9 316 U1 1 U2 4 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 AUG PY 1993 VL 14 IS 8 BP 1689 EP 1692 DI 10.1093/carcin/14.8.1689 PG 4 WC Oncology SC Oncology GA LT119 UT WOS:A1993LT11900033 PM 8102597 ER PT J AU LAKATTA, EG COHEN, JD FLEG, JL FROHLICH, ED GRADMAN, AH AF LAKATTA, EG COHEN, JD FLEG, JL FROHLICH, ED GRADMAN, AH TI HYPERTENSION IN THE ELDERLY - AGE-RELATED AND DISEASE-RELATED COMPLICATIONS AND THERAPEUTIC IMPLICATIONS SO CARDIOVASCULAR DRUGS AND THERAPY LA English DT Article DE ELDERLY HYPERTENSIVE; CARDIAC HYPERTROPHY; PERIPHERAL VASCULAR RESISTANCE; ARTERIAL IMPEDANCE; THERAPEUTIC CONSIDERATIONS ID CORONARY HEART-DISEASE; LEFT-VENTRICULAR HYPERTROPHY; BLOOD-PRESSURE; ECHOCARDIOGRAPHIC ASSESSMENT; ARTERY DISEASE; RENIN-ACTIVITY; MORTALITY; EXERCISE; SODIUM; HEMODYNAMICS AB Effective treatment of hypertension in the elderly requires an understanding of both the progressive course of the disease and the impact of aging on the cardiovascular system, including physiological, genetic, lifestyle, and environmental factors. Review of the literature that has attempted to define the impact of an ''aging process'' on cardiovascular structure and function reveals a diversity of findings and interpretations. However, in general, normotensive elderly subjects exhibit the heart and vascular characteristics of ''muted'' hypertension, including many features of younger hypertensive patients: cardiac hypertrophy, diminution in resting left ventricular early diastolic filling rate, increased arterial stiffness and aortic impedance, diminution in the baroreceptor reflex, a diminished response to catecholamines and diminished renal blood flow, and an increase in peripheral vascular resistance (PVR). Treatment of elderly hypertensives is more challenging because of the greater likelihood of the presence of concomitant diseases, most importantly, coronary and peripheral atherosclerosis, renal dysfunction, and diabetes mellitus. Isolated systolic hypertension (ISH), the most common form of hypertension in the elderly, has also been clearly shown to be an important predictor of cardiovascular morbidity and mortality, including coronary artery disease, congestive heart failure, and stroke. Treatment of ISH has been shown to lower systolic pressure safely and effectively in the elderly. By reducing PVR, and possibly the arterial stiffness, and thus the early reflected pulse waves, vasodilators, including calcium antagonists, may lower these three components of arterial impedance, and hence lower the arterial load on the heart. The cardiac hypertrophy and reduced left ventricular filling rate associated with hypertension in older individuals can also be ameliorated, to some extent, by calcium channel blockers. C1 ST LOUIS UNIV,PREVENT CARDIOL PROGRAM,ST LOUIS,MO 63103. ALTON OCHSNER MED FDN & OCHSNER CLIN,NEW ORLEANS,LA 70121. WESTERN PENN HOSP,DIV CARDIOVASC DIS,PITTSBURGH,PA 15224. RP LAKATTA, EG (reprint author), NATL INST AGING,GERONTOL RES CTR,CARDIOVASC SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 98 TC 16 Z9 16 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0920-3206 J9 CARDIOVASC DRUG THER JI Cardiovasc. Drugs Ther. PD AUG PY 1993 VL 7 IS 4 BP 643 EP 653 DI 10.1007/BF00877817 PG 11 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA LY225 UT WOS:A1993LY22500001 PM 8241007 ER PT J AU KRATZKE, RA SHIMIZU, E GERADTS, J GERSTER, JL SEGAL, S OTTERSON, GA KAYE, FJ AF KRATZKE, RA SHIMIZU, E GERADTS, J GERSTER, JL SEGAL, S OTTERSON, GA KAYE, FJ TI RB-MEDIATED TUMOR SUPPRESSION OF A LUNG-CANCER CELL-LINE IS ABROGATED BY AN EXTRACT ENRICHED IN EXTRACELLULAR-MATRIX SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID BASEMENT-MEMBRANE MATRIGEL; RETINOBLASTOMA PROTEIN; CARCINOMA-CELLS; C-MYC; GENE; EXPRESSION; TUMORIGENICITY; IDENTIFICATION; LAMININ; GROWTH AB To examine whether the expression of retinoblastoma (RB) protein could mediate tumor suppression in a lung carcinoma cell line carrying multiple genetic defects, we transfected the Rb gene into a non-small cell lung cancer cell line with absent RB protein. We observed that the stable expression of a functional RB product was associated with a decreased efficiency of soft agar cloning and partial suppression of tumorigenicity in nude mice. The suppression of tumorigenicity was marked when 10(6) cells were injected into the flanks of nude mice but was less prominent when 10(7) cells were injected. RB-mediated tumor suppression, however, was consistently blocked by preincubation of the transfected cells with an extract enriched with an extracellular matrix (Matrigel). Analysis of tumors harvested from nude mice showed that they continued to express detectable levels of human RB protein which retained functional E1A binding activity and nuclear localization. RB-mediated inhibition of soft agar cloning was also blocked in a dose-dependent manner by the addition of Matrigel. These observations demonstrate that the expression of wild-type RB may suppress certain parameters of tumorigenicity in lung carcinoma cells that contain multiple genetic alterations. In addition, the reversal of tumor suppression by an extract enriched in basement membrane components may offer clues for further investigations into the mechanism of RB-mediated tumor suppression. C1 MOLEC ONCOL INC,GAITHERSBURG,MD 20878. RP KRATZKE, RA (reprint author), NCI,NNMC,NAVY MED ONCOL BRANCH,BLDG 8,ROOM 5101,BETHESDA,MD 20889, USA. RI kaye, frederic/E-2437-2011 NR 32 TC 31 Z9 31 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 AUG PY 1993 VL 4 IS 8 BP 629 EP 635 PG 7 WC Cell Biology SC Cell Biology GA LR308 UT WOS:A1993LR30800002 PM 8398904 ER PT J AU MITSUDOMI, T LAM, S SHIRAKUSA, T GAZDAR, AF AF MITSUDOMI, T LAM, S SHIRAKUSA, T GAZDAR, AF TI DETECTION AND SEQUENCING OF P53 GENE-MUTATIONS IN BRONCHIAL BIOPSY SAMPLES IN PATIENTS WITH LUNG-CANCER SO CHEST LA English DT Article ID ABNORMALITIES; POLYMORPHISMS; FREQUENT; DNA AB We demonstrated the feasibility of detection of p53 gene mutations in bronchial biopsy samples from patients with lung cancer. Following DNA extraction from two to three pieces of bronchial tissue obtained by fiberoptic bronchoscopy, p53 gene mutations were screened using polymerase chain reaction/single-strand conformation polymorphism technique. We examined four bronchial biopsy specimens from patients with squamous cell carcinoma of the lung and detected one point mutation at codon 130 (C to G, Leu to Val). This technique will be very useful for studies on early detection of lung cancers or for an analysis of a suspected premalignant lesion. Furthermore, this technique enables us to know the status of oncogene or tumor suppressor gene at the time of diagnosis, which may be very useful for a treatment of patients with cancer in the not too distant future. C1 NCI, NAVY MED ONCOL BRANCH, BETHESDA, MD 20892 USA. NATL NAVAL MED CTR, BETHESDA, MD 20814 USA. UNIV OCCUPAT & ENVIRONM HLTH, SCH MED, DEPT SURG 2, KITAKYUSHU, FUKUOKA 807, JAPAN. VANCOUVER GEN HOSP, VANCOUVER V5Z 1M9, BC, CANADA. UNIV TEXAS, SW MED CTR, SIMMONS CANC CTR, DALLAS, TX 75230 USA. UNIV TEXAS, SW MED CTR, DEPT PATHOL, DALLAS, TX 75230 USA. RP MITSUDOMI, T (reprint author), UNIV OCCUPAT & ENVIRONM HLTH, DEPT SURG, 1-1 ISEIJANOKA, KAHATANISHI KU, KITAKYUSHU, FUKUOKA 807, JAPAN. OI Mitsudomi, Tetsuya/0000-0001-9860-8505 NR 25 TC 24 Z9 24 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 AUG PY 1993 VL 104 IS 2 BP 362 EP 365 DI 10.1378/chest.104.2.362 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA LT002 UT WOS:A1993LT00200011 PM 8393397 ER PT J AU POULEUR, H ROUSSEAU, MF VANEYLL, C STOLERU, L HAYASHIDA, W UDELSON, JA DOLAN, N KINAN, D GALLAGHER, P AHN, S BENEDICT, CR YUSUF, S KONSTAM, M AF POULEUR, H ROUSSEAU, MF VANEYLL, C STOLERU, L HAYASHIDA, W UDELSON, JA DOLAN, N KINAN, D GALLAGHER, P AHN, S BENEDICT, CR YUSUF, S KONSTAM, M TI EFFECTS OF LONG-TERM ENALAPRIL THERAPY ON LEFT-VENTRICULAR DIASTOLIC PROPERTIES IN PATIENTS WITH DEPRESSED EJECTION FRACTION SO CIRCULATION LA English DT Article DE ANGIOTENSIN CONVERTING ENZYME; LEFT VENTRICLE; EJECTION FRACTION ID CONGESTIVE-HEART-FAILURE; CONVERTING ENZYME-INHIBITION; NON-GEOMETRIC DETERMINATION; PRESSURE-VOLUME RELATIONS; BLOOD POOL SCANS; MYOCARDIAL-INFARCTION; ANGIOTENSIN; DYSFUNCTION; CAPTOPRIL; DISEASE AB Background. The aim of the present study was to analyze the changes in left ventricular diastolic function that occur in patients with chronic severe left ventricular systolic dysfunction in the absence or presence of prolonged therapy with an angiotensin converting enzyme inhibitor. Methods and Results. Left ventricular function data (cineangiography plus Millar, frame-by-frame analysis) and right ventricular volumes (radionuclide angiography) were obtained at baseline and after an average follow-up of 12.4 months in 42 patients with a left ventricular ejection fraction of 35% or less. After baseline measurements, the patients were randomized to placebo (n=16) or enalapril (10 mg BID, n=26). In the placebo group, the changes in left ventricular function were characterized by increases in end-diastolic (159+/-43 to 170+/-44 ML/M2 ) and end-systolic (119+/-38 to 128+/-49 mL/M2) volumes accompanied by a downward and rightward shift of the diastolic pressure-volume relation. In contrast, decreases in end-diastolic (166+/-43 to 156+/-47 mL/M2 ) and end-systolic (125+/-43 to 111+/-42 mL/m2) volumes accompanied by a slight upward and leftward shift of the diastolic pressure-volume relation were noted in the enalapril group. These changes in left ventricular volumes were significantly different between groups (both P<.005) but were not attended by changes in left ventricular end-diastolic pressure, in time constant of isovolumic pressure decrease, or in right ventricular volumes. However, the chamber stiffness constant 8 decreased from 0.044+/-0.027 to 0.032+/-0.019 mL-1/m2 in the placebo group, whereas it increased insignificantly in the enalapril group (0.040+/-0.028 to 0.041+/-0.028 mL-1/m2). These changes in chamber stiffness constant beta between baseline and follow-up were significantly different between placebo and enalapril groups (P<.05). Another index of chamber compliance, DELTA V/DELTA P, also confirmed the presence of opposite changes in left ventricular chamber compliance in the placebo group and in the enalapril group. The mean diastolic wall stress increased with placebo but not with enalapril (+51 versus - 13 kdyn/cm2; P<.04) whereas left ventricular mass and the indexes of left ventricular sphericity tended to improve in the enalapril group. The changes in plasma levels of norepinephrine, atrial natriuretic peptide, and arginine vasopressin were, however, comparable in both groups. Conclusions. The data indicate that in patients with severe systolic left ventricular dysfunction, the progressive left ventricular dilatation was accompanied by a decrease in left ventricular chamber stiffness; enalapril therapy was able to prevent or partially reverse these changes and tended to reduce left ventricular mass and ventricular sphericity. Those changes were suggestive of partial reversal of left ventricular remodeling by enalapril administration. C1 UNIV CATHOLIQUE LOUVAIN,SCH MED,DIV CARDIOL,B-1200 BRUSSELS,BELGIUM. TUFTS UNIV,NEW ENGLAND MED CTR,BOSTON,MA 02111. NHLBI,BETHESDA,MD 20892. UNIV N CAROLINA,CHAPEL HILL,NC 27514. UNIV TEXAS,HOUSTON,TX 77025. FU NHLBI NIH HHS [N01-HC-65030] NR 37 TC 57 Z9 57 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 AUG PY 1993 VL 88 IS 2 BP 481 EP 491 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA LR058 UT WOS:A1993LR05800019 PM 8101772 ER PT J AU KLUES, HG PROSCHAN, MA DOLLAR, AL SPIRITO, P ROBERTS, WC MARON, BJ AF KLUES, HG PROSCHAN, MA DOLLAR, AL SPIRITO, P ROBERTS, WC MARON, BJ TI ECHOCARDIOGRAPHIC ASSESSMENT OF MITRAL-VALVE SIZE IN OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY - ANATOMIC VALIDATION FROM MITRAL-VALVE SPECIMEN SO CIRCULATION LA English DT Article DE MITRAL VALVE; CARDIOMYOPATHIES; ECHOCARDIOGRAPHY ID SYSTOLIC ANTERIOR MOTION; CLINICAL MANIFESTATIONS; PRESSURE-GRADIENT; PATHO-PHYSIOLOGY; PROLAPSE; LEAFLET; PATTERNS; INTERRELATIONS; IDENTIFICATION; REGURGITATION AB Background. In patients with hypertrophic cardiomyopathy, obstruction to left ventricular outflow is produced by systolic anterior motion of the mitral valve. In many of these patients, the mitral leaflets are elongated and increased in overall size. Mitral valve size may be responsible, in part, for the presence and magnitude of the outflow gradient and the pattern of systolic anterior motion of the leaflets. It may also influence the effectiveness of ventricular septal myotomy-myectomy in relieving subaortic obstruction. Therefore, the present study was undertaken to determine whether mitral valve dimensions could be assessed in quantitative terms from the echocardiogram in patients with hypertrophic cardiomyopathy. Methods and Results. A group of 37 patients with hypertrophic cardiomyopathy was selected for this study by virtue of having a high-quality transthoracic or intraoperative echocardiogram suitable for certain quantitative measurements from stop-frame images as well as a morphologically intact mitral valve specimen (removed during surgery). Seven measurements of mitral valve dimensions were obtained from the two-dimensional and M-mode echocardiograms. A univariate regression analysis identified the mitral valve opening area as the best single predictor of actual mitral leaflet area measured from the specimen (r2=.75; r=.87). The linear relation between mitral valve opening area as assessed by two-dimensional echocardiography and actual mitral leaflet area measured from the mitral valve specimen accounted for approximately 75% of the variability in mitral leaflet area. With such statistical models, it was possible to reliably identify from the echocardiogram enlarged mitral valves (greater-than-or-equal-to 12.0 cm2) in 16 of 19 patients (84%) and normal-sized valves in 15 of 18 patients (83%). Conclusions. In a selected group of patients with obstructive hypertrophic cardiomyopathy, a model derived from a regression analysis of quantitative echocardiographic measurements permitted (with good precision) estimation of actual mitral leaflet area and consequently overall mitral valve size and the discrimination of enlarged from normal-sized mitral valves. C1 NHLBI,CARDIOL RES BRANCH,BETHESDA,MD 20892. NHLBI,BIOSTAT RES BRANCH,BETHESDA,MD 20892. NR 37 TC 46 Z9 47 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 AUG PY 1993 VL 88 IS 2 BP 548 EP 555 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA LR058 UT WOS:A1993LR05800026 PM 8339417 ER PT J AU FERRANS, VJ HALL, RJ MCALLISTER, HA AF FERRANS, VJ HALL, RJ MCALLISTER, HA TI CHLOROQUINE-INDUCED CARDIOMYOPATHY SO CIRCULATION LA English DT Article C1 ST LUKES EPISCOPAL HOSP,DEPT PATHOL,6720 BERTNER,MC 1-102,HOUSTON,TX 77030. ST LUKES EPISCOPAL HOSP,DEPT CARDIOL,HOUSTON,TX 77030. NHLBI,DEPT PATHOL,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 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 AUG PY 1993 VL 88 IS 2 BP 785 EP 786 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA LR058 UT WOS:A1993LR05800051 PM 8281631 ER PT J AU BERSON, A AF BERSON, A TI PIPBERGER,HUBERT,V. 1920-1993 - IN-MEMORIAM SO CIRCULATION LA English DT Item About an Individual RP BERSON, A (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 AUG PY 1993 VL 88 IS 2 BP 817 EP 818 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA LR058 UT WOS:A1993LR05800075 ER PT J AU XIAO, RP LAKATTA, EG AF XIAO, RP LAKATTA, EG TI BETA-1-ADRENOCEPTOR STIMULATION AND BETA-2-ADRENOCEPTOR STIMULATION DIFFER IN THEIR EFFECTS ON CONTRACTION, CYTOSOLIC CA2+, AND CA2+ CURRENT IN SINGLE-RAT VENTRICULAR CELLS SO CIRCULATION RESEARCH LA English DT Article DE CARDIAC CELLS; BETA-ADRENERGIC RECEPTOR SUBTYPES; CA2+ TRANSIENT; CONTRACTION; CA2+ CURRENT ID BETA-ADRENOCEPTOR POPULATIONS; ADENYLATE-CYCLASE STIMULATION; CARDIAC MYOCYTES; CYCLIC-AMP; ADRENERGIC-RECEPTORS; HUMAN-HEART; QUANTITATIVE AUTORADIOGRAPHY; CA-2+ TRANSIENTS; SINOATRIAL NODE; PROTEIN-KINASE AB The effects of beta2- and beta1 -adrenoceptor (beta2AR and beta1AR, respectively) agonists on the cytosolic Ca2+ (Ca(i)) transient (indexed by the transient increase in indo-1 fluorescence ratio after excitation), twitch amplitude (measured via photodiode array), membrane potential, and L-type sarcolemmal Ca2+ current (I(Ca), measured by whole-cell patch electrode) were assessed in single rat ventricular myocytes. The selective beta2AR agonist Zinterol increased the amplitudes of both the Ca(i) transient and twitch in a concentration-dependent manner. Similar results were obtained when beta2ARs were stimulated with isoproterenol in the presence of the selective beta1AR antagonist CGP 20712A. beta1AR stimulation induced by norepinephrine increased twitch amplitude to about the same extent as did beta2AR stimulation. However, several striking differences between response to beta1AR and beta2AR stimulation were observed. Beta1AR stimulation had the potent effect of abbreviating the time course of the contraction and Ca(i) transient, and beta2AR stimulation did not reduce the time course of the Ca(i) transient and had only a minor effect on the twitch duration. For a given increase in twitch amplitude, beta1AR stimulation caused a greater increase in Ca(i) transient, suggesting a diminished Ca(i)-myofilament interaction. Beta1AR, but not beta2AR, stimulation evoked spontaneous Ca(i) oscillations, increased the diastolic indo fluorescence level, and caused a decline in resting cell length. Beta1AR and beta2AR also differed in their effects on I(Ca). Whereas both beta1AR and beta2AR stimulation increased the peak I(Ca). amplitude, beta2AR stimulation markedly prolonged the I(Ca) inactivation time. Accordingly, beta2AR stimulation prolonged the action potential duration to a greater extent than did beta1AR stimulation. 8-(4-Chlorophenylthio)cAMP mimicked the effects of beta1AR stimulation by norepinephrine but not those due to beta2AR stimulation. These results clearly indicate that both beta2ARs and beta1ARs functionally coexist in rat ventricular myocytes but that stimulation of these receptor subtypes elicits qualitatively different cell responses at the levels of ionic channels, the myofilaments, and sarcoplasmic reticulum. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224. NR 56 TC 191 Z9 201 U1 0 U2 7 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD AUG PY 1993 VL 73 IS 2 BP 286 EP 300 PG 15 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA LN561 UT WOS:A1993LN56100009 PM 8101141 ER PT J AU GRADON, JD STEIN, DS AF GRADON, JD STEIN, DS TI ASSOCIATION BETWEEN ROCHALIMAEA INFECTION AND CAT-SCRATCH DISEASE SO CLINICAL INFECTIOUS DISEASES LA English DT Letter RP GRADON, JD (reprint author), NIAID,DIV AIDS,MED BRANCH,6003 EXECUT BLVD,ROOM 2C25,ROCKVILLE,MD 20852, USA. NR 4 TC 5 Z9 5 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG PY 1993 VL 17 IS 2 BP 287 EP 287 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA LP455 UT WOS:A1993LP45500031 PM 8399887 ER PT J AU BIGGAR, RJ ROSENBERG, PS AF BIGGAR, RJ ROSENBERG, PS TI HIV-INFECTION AIDS IN THE UNITED-STATES DURING THE 1990S SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HOMOSEXUAL MEN; AIDS EPIDEMIC; DRUG-USERS; TRANSMISSION; TRENDS; RISK; SEROCONVERSION; PREVALENCE; POPULATION AB Estimates derived by backcalculation indicate that 628,000 to 988,000 Americans had become infected with human immunodeficiency virus (HIV) as of 1 January 1991. In persons exposed heterosexually, the incidence of HIV infection is still increasing, but in other groups, it is stable or decreasing from peak rates that occurred in the early and mid-1980s. If one assumes a 9-year median incubation period between the time of HIV infection and AIDS in untreated persons, our models yielded a best-fit estimate of 637,000 ever-infected persons as of 1 January 1991. From this population, we projected a plateau of about 55,000 incident cases of AIDS per year between 1991 and 1994, with more cases occurring among drug users than among homosexual men after 1994. Backcalculation models that use a 10-year median incubation period yielded a plausible upper-bound estimate of 988,000 ever-infected persons, and projections of AIDS incidence increased to approximately 70,000 new cases per year by 1994, the majority in homosexual men. Using either model, we project that the number of AIDS cases attributed to heterosexual exposure will increase steadily. C1 NCI, VIRAL EPIDEMIOL SECT, BETHESDA, MD 20892 USA. NCI, EPIDEMIOL METHODS SECT, BETHESDA, MD 20892 USA. NR 31 TC 4 Z9 4 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG PY 1993 VL 17 SU 1 BP S219 EP S223 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA LQ130 UT WOS:A1993LQ13000036 PM 8399920 ER PT J AU DIMITROV, DS FRANZOSO, G SALMAN, M BLUMENTHAL, R TARSHIS, M BARILE, MF ROTTEM, S AF DIMITROV, DS FRANZOSO, G SALMAN, M BLUMENTHAL, R TARSHIS, M BARILE, MF ROTTEM, S TI MYCOPLASMA-FERMENTANS (INCOGNITUS STRAIN) CELLS ARE ABLE TO FUSE WITH T-LYMPHOCYTES SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT INTERNATIONAL SYMP ON THE CHANGING ROLE OF MYCOPLASMAS IN RESPIRATORY DISEASE AND AIDS CY NOV 30-DEC 05, 1991 CL SCOTTSDALE, AZ ID INFECTIVITY; INHIBITION; VESICLES; BINDING; VIRUSES; FUSION; AIDS AB Characteristics of the fusion of Mycoplasma fermentans (incognitus strain) with cultured lymphocytes were investigated. The rate and extent of fusion were monitored continuously in an assay that measured lipid mixing on the basis of dequenching of a fluorescent probe, octadecylrhodamine (R18), incorporated into mycoplasmas. Fusion of M. fermentans was detected with CD4+ (Molt-3) cells, CD4- (12E1) cells, and primary peripheral-blood lymphocytes. The level of fusion was relatively low (8%-12%). Detection of a similarly low level of fusion by fluorescence microscopy suggested the involvement of a specific lymphocyte subpopulation. After a short lag period, fusion at 37-degrees-C proceeded exponentially for approximately 30 minutes and was virtually complete at 60 minutes. Throughout the process, lymphocytes remained intact. Fusion was stimulated by CaCl2 but not by MgCl2; its inhibition by antisera to M. fermentans and by pretreatment of M. fermentans with proteolytic enzymes implied that the mycoplasmas possessed a proteinase-sensitive receptor involved in fusion. Mycoplasmas were rendered nonfusogenic by treatment with the uncoupler CCCP (carbonyl cyanide m-chlorophenylhydrazone; 5 muM) but were unaffected by treatment with chlorpromazine (10 muM) or DCCD (dicyclohexylcarbodiimide; 50 muM); these findings suggested that a proton gradient across the cell membrane is required for fusion. C1 HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT MEMBRANE & ULTRASTRUCT RES,POB 1172,IL-91010 JERUSALEM,ISRAEL. NCI,MATH BIOL LAB,MEMBRANE STRUCT & FUNCT SECT,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,MYCOPLASMA LAB,BETHESDA,MD 20014. NR 19 TC 11 Z9 11 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG PY 1993 VL 17 SU 1 BP S305 EP S308 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA LQ130 UT WOS:A1993LQ13000051 PM 8399933 ER PT J AU LO, SC WEAR, DJ SHIH, JWK WANG, RYH NEWTON, PB RODRIGUEZ, JF AF LO, SC WEAR, DJ SHIH, JWK WANG, RYH NEWTON, PB RODRIGUEZ, JF TI FATAL SYSTEMIC INFECTIONS OF NONHUMAN-PRIMATES BY MYCOPLASMA-FERMENTANS (INCOGNITUS STRAIN) SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT INTERNATIONAL SYMP ON THE CHANGING ROLE OF MYCOPLASMAS IN RESPIRATORY DISEASE AND AIDS CY NOV 30-DEC 05, 1991 CL SCOTTSDALE, AZ ID AGENT VLIA; VIRUS; AIDS; CHIMPANZEES; GENITALIUM AB Four silvered leaf monkeys inoculated with Mycoplasma fermentans (incognitus strain) showed wasting syndromes and died in 7-9 months. Infected animals had a late and transient antibody response to mycoplasmal infection. Three monkeys revealed periodic mycoplasmal antigenemia. The one that had the most persistent antigenemia failed to mount a detectable antibody response and was the first to die of the infection. The control monkey was killed 8 months later, after the last of the infected animals had died, and revealed no evidence of seroconversion or antigenemia. Polymerase chain reaction, immunohistochemical, and electron microscopic studies identified systemic infections of M. fermentans in the infected animals. No other opportunistic infection or neoplastic disease was found. It is interesting to note the absence of an inflammatory reaction to the large number of mycoplasmas in the infected tissues. M. fermentans (incognitus strain) apparently suppressed normal inflammatory or immune responses, produced wasting syndromes, and caused a fatal systemic infection in these monkeys. C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. RP LO, SC (reprint author), ARMED FORCES INST PATHOL,DEPT INFECT & PARASIT DIS PATHOL,AMER REGISTRY PATHOL,WASHINGTON,DC 20306, USA. NR 9 TC 15 Z9 15 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG PY 1993 VL 17 SU 1 BP S283 EP S288 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA LQ130 UT WOS:A1993LQ13000048 PM 8399931 ER PT J AU POLI, G PANTALEO, G FAUCI, AS AF POLI, G PANTALEO, G FAUCI, AS TI IMMUNOPATHOGENESIS OF HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT INTERNATIONAL SYMP ON THE CHANGING ROLE OF MYCOPLASMAS IN RESPIRATORY DISEASE AND AIDS CY NOV 30-DEC 05, 1991 CL SCOTTSDALE, AZ ID TUMOR NECROSIS FACTOR; GROWTH-FACTOR-BETA; LONG TERMINAL REPEAT; PRIMARY MONONUCLEAR PHAGOCYTES; DEFICIENCY SYNDROME AIDS; TYPE-1 HIV-1 INFECTION; HUMAN PERIPHERAL-BLOOD; T-CELL CLONE; LYMPHOCYTES-T; FACTOR-ALPHA AB Infection with human immunodeficiency virus (HIV) causes AIDS. As a consequence of the interaction of gp120 envelope with the CD4 receptor molecule expressed by a subset of T lymphocytes and by mononuclear phagocytes (MPs), a second envelope protein (gp41) mediates fusion of the virion membrane with the target membrane. In these events the role of adhesion molecules such as LFA-1 has recently been highlighted. Following viral entry, reverse transcription of the virion-associated RNA and integration of proviral DNA into the host genome are crucial steps in HIV infection, which can lead to expression of high levels of new HIV or to silent infection for indefinite periods, a condition defined as viral latency. Several factors in addition to endogenous viral regulatory proteins have been reported as capable of modulating the state of viral latency and expression in vitro, including the cytokine network that normally modulates immune homeostasis as well as the immune response to inflammatory stimuli. Finally, recent studies have underscored the observation that the CD4+ T lymphocytes are the major reservoir of HIV in the peripheral blood compartment and in the lymphoid tissues, which are characterized by a greater viral burden, whereas in nonlymphoid organs such as the brain and the lung, local infection is predominantly sustained by MPs. RP POLI, G (reprint author), NIAID,IMMUNOREGULAT LAB,ROOM 6A33A,BLDG 10A,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Pantaleo, Giuseppe/K-6163-2016 NR 83 TC 26 Z9 26 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG PY 1993 VL 17 SU 1 BP S224 EP S229 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA LQ130 UT WOS:A1993LQ13000037 PM 8104513 ER PT J AU TULLY, JG AF TULLY, JG TI CURRENT STATUS OF THE MOLLICUTE FLORA OF HUMANS SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID MYCOPLASMA-HOMINIS INFECTION; CENTRAL NERVOUS-SYSTEM; PROSTHETIC VALVE ENDOCARDITIS; NEWLY DISCOVERED MYCOPLASMA; LIVER-TRANSPLANT RECIPIENT; AMNIOTIC-FLUID INFECTION; STEVENS-JOHNSON SYNDROME; HUMAN UROGENITAL TRACT; CHRONIC LUNG-DISEASE; UREAPLASMA-UREALYTICUM AB Of the more than 20 species of mollicutes reported to be present in human tissues, 15 have been isolated more than once and are currently thought to typify mollicutes of human origin. In the past decade a number of new and potentially significant mollicutes have been added to the list of species inhabiting humans. As our understanding of the human mollicute flora increases, diagnostic and clinical advances should permit the identification and control of those species that are significant pathogens in human disease. RP TULLY, JG (reprint author), NIAID, FREDERICK CANC RES & DEV CTR, MOLEC MICROBIOL LAB, MYCOPLASMA SECT, BLDG 550, FREDERICK, MD 21702 USA. NR 158 TC 33 Z9 35 U1 2 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG PY 1993 VL 17 SU 1 BP S2 EP S9 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA LQ130 UT WOS:A1993LQ13000002 PM 8399915 ER PT J AU TULLY, JG SHIH, JWK WANG, RHY ROSE, DL LO, SC AF TULLY, JG SHIH, JWK WANG, RHY ROSE, DL LO, SC TI TITERS OF ANTIBODY TO MYCOPLASMA IN SERA OF PATIENTS INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT INTERNATIONAL SYMP ON THE CHANGING ROLE OF MYCOPLASMAS IN RESPIRATORY DISEASE AND AIDS CY NOV 30-DEC 05, 1991 CL SCOTTSDALE, AZ ID SEROLOGICAL CROSS-REACTIONS; GENITALIUM; STRAINS; PNEUMONIAE AB One hundred sixty-seven sera collected from human immunodeficiency virus (HIV)-negative blood donors (n = 41), asymptomatic HIV-positive patients (n = 75), and patients with AIDS (n = 51) were compared in a metabolism inhibition serological test employing antigens to four distinct Mycoplasma species. The proportion of sera with antibody titers of greater-than-or-equal-to 1:32 to Mycoplasma genitalium was significantly higher for patients with AIDS than for HIV-negative blood donors. Serological relationships between Mycoplasma pneumoniae and M. genitalium as well as the possibility of increased susceptibility of AIDS patients to infection with these two mycoplasmas might account for this finding. Few sera showed antibody responses to Mycoplasma pirum or Mycoplasma fermentans. C1 ARMED FORCES INST PATHOL,DEPT INFECT & PARASIT DIS PATHOL,WASHINGTON,DC 20306. NIH,CTR CLIN,DEPT TRANSFUS MED,BETHESDA,MD 20892. RP TULLY, JG (reprint author), NIAID,FREDERICK CANC RES & DEV CTR,MYCOPLASMA SECT,BLDG 550,FREDERICK,MD 21702, USA. NR 24 TC 14 Z9 14 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG PY 1993 VL 17 SU 1 BP S254 EP S258 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA LQ130 UT WOS:A1993LQ13000042 PM 8399925 ER PT J AU TABAS, JA HAHN, GV COHEN, RB SEAUNEZ, HN MODI, WS WOZNEY, JM ZASLOFF, M KAPLAN, FS AF TABAS, JA HAHN, GV COHEN, RB SEAUNEZ, HN MODI, WS WOZNEY, JM ZASLOFF, M KAPLAN, FS TI CHROMOSOMAL ASSIGNMENT OF THE HUMAN GENE FOR BONE MORPHOGENETIC PROTEIN-4 SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID HOLT-ORAM SYNDROME; IDENTIFICATION; MOUSE; BMP2A AB Bone morphogenetic proteins (BMP) are the only known biologic factors capable of inducing endochondral ossification at an extraskeletal site. Seven members of the BMP family have been identified thus far and are involved in osteoinduction and morphogenesis. The authors established the chromosomal assignment of the gene for BMP4 on human chromosome 14 by using somatic cell hybrid panels and molecular technology. The genetic map of chromosome 14 shows that Holt-Oram Syndrome (HOS), a heritable disorder of skeletal and cardiac development, may be located also on chromosome 14. Linkage analysis studies in large families with HOS will determine if the BMP4 gene is related to HOS. In addition, analysis shows that the BMP4 gene maps to a conserved region of the mouse and human genomes. The chromosomal locus of a gene is part of human anatomy and provides a genomic landmark for studies on the pathogenesis of heritable disorders. C1 HOSP UNIV PENN,DEPT ORTHOPAED SURG,METAB BONE DIS SERV,SILVERSTEIN 2-3400 SPRUCE ST,PHILADELPHIA,PA 19104. CHILDRENS HOSP PHILADELPHIA,DIV HUMAN GENET & MOLEC BIOL,PHILADELPHIA,PA. NCI,PROGRAM RESOURCES DYNCORP,LAB BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21701. GENET INST INC,TISSUE GROWTH & REPAIR PROGRAM,CAMBRIDGE,MA. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. UNIV PENN,SCH MED,DEPT ORTHOPAED SURG,PHILADELPHIA,PA 19104. NR 33 TC 14 Z9 14 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD AUG PY 1993 IS 293 BP 310 EP 316 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA LR863 UT WOS:A1993LR86300042 PM 8339498 ER PT J AU RUTTIMANN, UE POLLACK, MM AF RUTTIMANN, UE POLLACK, MM TI A TIME-SERIES APPROACH TO PREDICT OUTCOME FROM PEDIATRIC INTENSIVE-CARE SO COMPUTERS AND BIOMEDICAL RESEARCH LA English DT Article ID CRITICALLY ILL PATIENTS; LIFE SUPPORT; UNIT PATIENTS; MORTALITY; WITHDRAWAL; SEVERITY; THERAPY; RESUSCITATION; MEDICINE; JUDGMENT C1 GEORGE WASHINGTON UNIV,SCH MED,WASHINGTON,DC 20052. CHILDRENS HOSP,NATL MED CTR,DEPT PEDIAT,WASHINGTON,DC 20010. CHILDRENS HOSP,NATL MED CTR,DEPT ANESTHESIOL,WASHINGTON,DC 20010. CHILDRENS HOSP,NATL MED CTR,DEPT CRIT CARE MED,WASHINGTON,DC 20010. RP RUTTIMANN, UE (reprint author), NIAAA,CLIN STUDIES LAB,9000 ROCKVILLE PIKE,10-1N104,BETHESDA,MD 20892, USA. FU ORS NIH HHS [OR851115-015-2] NR 26 TC 2 Z9 2 U1 1 U2 2 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 AUG PY 1993 VL 26 IS 4 BP 353 EP 372 DI 10.1006/cbmr.1993.1025 PG 20 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA LU237 UT WOS:A1993LU23700004 PM 8403859 ER PT J AU BENICHOU, J AF BENICHOU, J TI A COMPUTER-PROGRAM FOR ESTIMATING INDIVIDUALIZED PROBABILITIES OF BREAST-CANCER SO COMPUTERS AND BIOMEDICAL RESEARCH LA English DT Article ID DISEASE; RISK RP BENICHOU, J (reprint author), NCI,BIOSTAT BRANCH,6130 EXECUT BLVD,EPN-403,ROCKVILLE,MD 20892, USA. NR 11 TC 30 Z9 30 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 0010-4809 J9 COMPUT BIOMED RES JI Comput. Biomed. Res. PD AUG PY 1993 VL 26 IS 4 BP 373 EP 382 DI 10.1006/cbmr.1993.1026 PG 10 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA LU237 UT WOS:A1993LU23700005 PM 8403860 ER PT J AU KORN, EL YU, KF MILLER, LL AF KORN, EL YU, KF MILLER, LL TI STOPPING A CLINICAL-TRIAL VERY EARLY BECAUSE OF TOXICITY - SUMMARIZING THE EVIDENCE SO CONTROLLED CLINICAL TRIALS LA English DT Article DE BAYESIAN ANALYSIS; CONFIDENCE INTERVAL; EARLY STOPPING; FISHERS EXACT TEST; GROUP SEQUENTIAL DESIGN; NUISANCE PARAMETER; SEQUENTIAL ANALYSIS ID CONTINGENCY-TABLES; EQUALITY; TESTS AB When a trial is stopped early because of a specific toxicity, it may be important to summarize the statistical evidence for stopping. Such a summary needs to take into account the sequential nature of the stopping rule. We address some practical issues involved in analyzing such toxicity data coming from a trial that was stopped after the fourth patient was evaluated. C1 NICHHD,BIOMETRY & MATH STAT BRANCH,BETHESDA,MD 20892. NCI,INVEST DRUG BRANCH,BETHESDA,MD 20892. RP KORN, EL (reprint author), NCI,BIOMETR RES BRANCH,CANC THERAPY EVALUAT PROGRAM EPN-739,BETHESDA,MD 20892, USA. NR 23 TC 9 Z9 9 U1 0 U2 0 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 AUG PY 1993 VL 14 IS 4 BP 286 EP 295 DI 10.1016/0197-2456(93)90226-4 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA LQ020 UT WOS:A1993LQ02000004 PM 7689943 ER PT J AU BEVAN, MJ SHER, A AF BEVAN, MJ SHER, A TI EDITORIAL OVERVIEW - LESSONS ON THE IMMUNE-RESPONSE FROM THE WAR ON BUGS SO CURRENT OPINION IN IMMUNOLOGY LA English DT Editorial Material C1 NIAID,IMMUNOL & CELL BIOL SECT,PARASIT DIS LAB,BETHESDA,MD 20892. RP BEVAN, MJ (reprint author), UNIV WASHINGTON,HOWARD HUGHES MED INST,DEPT IMMUNOL,SL-15,SEATTLE,WA 98195, USA. NR 1 TC 2 Z9 2 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 AUG PY 1993 VL 5 IS 4 BP 477 EP 478 DI 10.1016/0952-7915(93)90025-N PG 2 WC Immunology SC Immunology GA LU975 UT WOS:A1993LU97500001 ER PT J AU MODLIN, RL NUTMAN, TB AF MODLIN, RL NUTMAN, TB TI TYPE-2 CYTOKINES AND NEGATIVE IMMUNE REGULATION IN HUMAN INFECTIONS SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID T-CELL CLONES; TUMOR-NECROSIS-FACTOR; INTERFERON-GAMMA PRODUCTION; MYCOBACTERIUM-TUBERCULOSIS; SCHISTOSOMA-MANSONI; HELMINTH INFECTIONS; LEPROSY LESIONS; IFN-GAMMA; IL-4; ONCHOCERCIASIS AB Recent studies indicate that the human immune response to infection is regulated by the balance between the T helper type 1 cytokines. interleukin-2 and interferon-gamma, and the T helper type 2 cytokines. interleukin-4, interleukin-5 and interleukin-10. Interleukin-4 and interleukin-10 can facilitate antibody production but can also suppress cell-mediated immune responses. The net effect of these negative immunoregulatory cytokines is to favor progression of infection. C1 NIAID, PARASIT DIS LAB, BETHESDA, MD 20892 USA. RP MODLIN, RL (reprint author), UNIV CALIF LOS ANGELES, SCH MED, DIV DERMATOL, 10833 LE CONTE AVE, LOS ANGELES, CA 90024 USA. RI Modlin, Robert/M-7941-2014 OI Modlin, Robert/0000-0003-4720-031X FU NIAID NIH HHS [AI 22553]; NIAMS NIH HHS [AR 40312] NR 51 TC 101 Z9 109 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD AUG PY 1993 VL 5 IS 4 BP 511 EP 517 DI 10.1016/0952-7915(93)90031-M PG 7 WC Immunology SC Immunology GA LU975 UT WOS:A1993LU97500007 PM 8216926 ER PT J AU JAMES, SL NACY, C AF JAMES, SL NACY, C TI EFFECTOR FUNCTIONS OF ACTIVATED MACROPHAGES AGAINST PARASITES SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID TUMOR-NECROSIS-FACTOR; NITRIC-OXIDE SYNTHASE; COLONY-STIMULATING FACTOR; GROWTH-FACTOR-BETA; ENTAMOEBA-HISTOLYTICA TROPHOZOITES; MURINE PERITONEAL-MACROPHAGES; PLASMODIUM-FALCIPARUM INVITRO; FACTOR-ALPHA; L-ARGININE; IFN-GAMMA AB Evidence in experimental animals indicates a major role for cytokine-activated macrophages as effector cells in protective immunity against parasites. Research on cytokine function during this past year has contributed many insights into the immune mechanisms regulating murine macrophage function as well as the effector molecules employed by these cells to kill both intracellular and extracellular parasites. C1 ENTREMED INC, ROCKVILLE, MD 20850 USA. RP JAMES, SL (reprint author), NIAID, PARASIT DIS LAB, BETHESDA, MD 20892 USA. NR 55 TC 58 Z9 58 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 EI 1879-0372 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD AUG PY 1993 VL 5 IS 4 BP 518 EP 523 DI 10.1016/0952-7915(93)90032-N PG 6 WC Immunology SC Immunology GA LU975 UT WOS:A1993LU97500008 PM 8216927 ER PT J AU KASLOW, DC AF KASLOW, DC TI TRANSMISSION-BLOCKING IMMUNITY AGAINST MALARIA AND OTHER VECTOR-BORNE DISEASES SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID SEXUAL STAGE ANTIGENS; PAPUA-NEW-GUINEA; FALCIPARUM GAMETOCYTE ANTIGENS; VACCINE CANDIDATE ANTIGENS; GAMETE SURFACE-ANTIGENS; PLASMODIUM-FALCIPARUM; MONOCLONAL-ANTIBODIES; PERITROPHIC MEMBRANE; MOSQUITO ANTIBODIES; MINIMAL VARIATION AB Antibodies to sexual stage malaria parasites block transmission of Plasmodium by female mosquitoes. With the recent isolation of genes encoding several of the target antigens of transmission-blocking antibodies, the development of a subunit transmission-blocking vaccine against malaria is now a realistic goal. RP KASLOW, DC (reprint author), NIAID,MALARIA RES LAB,MOLEC VACCINE SECT,BLDG 4,ROOM B1-37,BETHESDA,MD 20892, USA. NR 54 TC 84 Z9 85 U1 1 U2 3 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 AUG PY 1993 VL 5 IS 4 BP 557 EP 565 DI 10.1016/0952-7915(93)90037-S PG 9 WC Immunology SC Immunology GA LU975 UT WOS:A1993LU97500013 PM 8216932 ER PT J AU KOZIOL, DE HENDERSON, DK AF KOZIOL, DE HENDERSON, DK TI RISK ANALYSIS AND OCCUPATIONAL EXPOSURE TO HIV AND HBV SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Article AB As the risk for occupational infection with bloodborne pathogens continues to be a source of substantial concern for health care providers, studies analyzing and assessing these risks assume added importance. During the past year several studies have provided additional insight into: the magnitude of risk for occupational infection with hepatitis B virus and HIV; the epidemiology of occupational exposures to blood; the epidemiology of occupational infection with bloodborne pathogens; and the efficacy of various interventional strategies designed to reduce risks for occupational exposures to blood and other related substances. This article reviews these studies and attempts to place the added information from them in perspective within the existing information base. RP KOZIOL, DE (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,BLDG 10,ROOM 4A21,BETHESDA,MD 20892, USA. NR 0 TC 12 Z9 13 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0951-7375 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD AUG PY 1993 VL 6 IS 4 BP 506 EP 510 DI 10.1097/00001432-199308000-00003 PG 5 WC Infectious Diseases SC Infectious Diseases GA LQ292 UT WOS:A1993LQ29200004 ER PT J AU MILLS, JL SIMPSON, JL AF MILLS, JL SIMPSON, JL TI PROSPECTS FOR PREVENTION OF NEURAL-TUBE DEFECTS BY VITAMIN SUPPLEMENTATION SO CURRENT OPINION IN NEUROLOGY AND NEUROSURGERY LA English DT Article ID PERICONCEPTIONAL USE AB Recent studies have resolved the debate over the role of vitamins in preventing neural tube defects. The British Medical Research Council trial demonstrated that 4 mg of folate daily, but not other vitamins, prevented 72% of recurrences. The Hungarian trial prevented neural tube defects in women who had not previously had affected children by giving multivitamins containing 0.8 mg of folate. The US Public Health Service currently recommends that women at risk for becoming pregnant take 0.4 mg of folate daily. Unfortunately, most pregnancies are unplanned, and women not planning to become pregnant may not follow this recommendation. Therefore, the US Food and Drug Administration is exploring methods of food fortification. Because large doses of folate have been reported to ameliorate B-12 deficiency anemia while allowing neurologic damage to progress, and to cause electroencephalogram abnormalities in epileptics, it is important to plan fortification carefully and to monitor both toxicity and benefits. C1 UNIV TENNESSEE CTR HLTH SCI,DEPT OBSTET & GYNECOL,MEMPHIS,TN 38163. RP MILLS, JL (reprint author), NICHHD,6100 BLDG,ROOM 7B03,BETHESDA,MD 20892, USA. NR 18 TC 2 Z9 3 U1 0 U2 0 PU CURRENT SCIENCE LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0951-7383 J9 CURR OPIN NEUROL NEU PD AUG PY 1993 VL 6 IS 4 BP 554 EP 558 PG 5 WC Neurosciences SC Neurosciences & Neurology GA LN915 UT WOS:A1993LN91500009 PM 8400468 ER PT J AU DAWIDOWICZ, EA AF DAWIDOWICZ, EA TI LIPID SORTING AND TRAFFICKING IN CELLS SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Article ID LIPOPROTEIN-DERIVED CHOLESTEROL; ENDOPLASMIC-RETICULUM; TRANSPORT; METABOLISM; MEMBRANE; PROTEIN AB Recent advances in the field of lipid sorting include the report of a cell-tree system that exhibits ATP-dependent transport of phosphatidylserine to mitochondria. Other investigations describe co-transport of glycosphingolipids with proteins, intra-Golgi movement of gangliosides and mobilization of cholesterol from lysosomes. In addition, the role of transfer proteins in intracellular lipid movement has again been challenged. RP DAWIDOWICZ, EA (reprint author), NIGMS,WESTWOOD BLDG,ROOM 621,5333 WESTBARD AVE,BETHESDA,MD 20892, USA. NR 16 TC 3 Z9 3 U1 0 U2 0 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 AUG PY 1993 VL 3 IS 4 BP 495 EP 498 DI 10.1016/0959-440X(93)90073-T PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LX181 UT WOS:A1993LX18100005 ER PT J AU MILLAR, SE LADER, ES DEAN, J AF MILLAR, SE LADER, ES DEAN, J TI ZAP-1 DNA-BINDING ACTIVITY IS 1ST DETECTED AT THE ONSET OF ZONA-PELLUCIDA GENE-EXPRESSION IN EMBRYONIC MOUSE OOCYTES SO DEVELOPMENTAL BIOLOGY LA English DT Article ID SPERM RECEPTOR; DEVELOPMENTAL REGULATION; GENOMIC ORGANIZATION RP MILLAR, SE (reprint author), NIDDK,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20814, USA. NR 14 TC 29 Z9 29 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG PY 1993 VL 158 IS 2 BP 410 EP 413 DI 10.1006/dbio.1993.1199 PG 4 WC Developmental Biology SC Developmental Biology GA LN777 UT WOS:A1993LN77700012 PM 8344459 ER PT J AU BALLOCK, RT HEYDEMANN, A WAKEFIELD, LM FLANDERS, KC ROBERTS, AB SPORN, MB AF BALLOCK, RT HEYDEMANN, A WAKEFIELD, LM FLANDERS, KC ROBERTS, AB SPORN, MB TI TGF-BETA-1 PREVENTS HYPERTROPHY OF EPIPHYSEAL CHONDROCYTES - REGULATION OF GENE-EXPRESSION FOR CARTILAGE MATRIX PROTEINS AND METALLOPROTEASES SO DEVELOPMENTAL BIOLOGY LA English DT Article ID TRANSFORMING GROWTH-FACTOR; BONE CELL-POPULATIONS; FACTOR-TYPE-BETA; TGF-BETA; TISSUE INHIBITOR; RNA EXPRESSION; RETINOIC ACID; MESSENGER-RNA; HUMAN BREAST; COLLAGENASE RP BALLOCK, RT (reprint author), NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892, USA. NR 66 TC 167 Z9 171 U1 0 U2 6 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG PY 1993 VL 158 IS 2 BP 414 EP 429 DI 10.1006/dbio.1993.1200 PG 16 WC Developmental Biology SC Developmental Biology GA LN777 UT WOS:A1993LN77700013 PM 8344460 ER PT J AU EASTMAN, RC SILVERMAN, R HARRIS, M JAVITT, JC CHIANG, YP GORDEN, P AF EASTMAN, RC SILVERMAN, R HARRIS, M JAVITT, JC CHIANG, YP GORDEN, P TI LESSENING THE BURDEN OF DIABETES - INTERVENTION STRATEGIES SO DIABETES CARE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; UNITED-STATES POPULATION; CORONARY HEART-DISEASE; CARDIOVASCULAR-DISEASE; INSULIN RESISTANCE; PHYSICAL-ACTIVITY; PIMA-INDIANS; RISK FACTOR; FOLLOW-UP; MELLITUS AB OBJECTIVE - To evaluate the impact of primary and secondary interventions on the development of complications from diabetes, we modeled the effects of primary and secondary interventions for diabetes on a single well-studied complication, diabetic retinopathy. RESEARCH DESIGN AND METHODS- A model was developed to predict cumulative incidence of retinopathy in IDDM and NIDDM. Risk functions are based on duration of diabetes. The effects of intervention strategies were simulated by altering the retinopathy risk. The effects of the simulations were assessed using cumulative incidence. RESULTS - Simulations of delaying the onset of IDDM from 2 to 8 yr and decreasing the retinopathy rates by 20-80% were performed for each type of retinopathy. Simulating primary prevention shifted the cumulative incidence curves to the right, and simulating secondary intervention shifted the curves downward. Primary prevention was less effective than secondary prevention. This difference was more apparent for IDDM than for NIDDM, where disease duration and exposure to retinopathy risk were shorter. All interventions shifted the development of retinopathy to later in life. CONCLUSIONS- The greatest effect on cumulative incidence of all forms of retinopathy occurs when primary and secondary interventions are combined. C1 GEORGETOWN UNIV, SCH MED, WORTHEN CTR EYE CARE RES, DEPT OPHTHALMOL, WASHINGTON, DC USA. RP EASTMAN, RC (reprint author), NIDDKD, DIV DIABET ENDOCRINOL & METAB DIS, BLDG 31, ROOM 9A-16, BETHESDA, MD 20892 USA. NR 59 TC 27 Z9 27 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD AUG PY 1993 VL 16 IS 8 BP 1095 EP 1102 DI 10.2337/diacare.16.8.1095 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LN778 UT WOS:A1993LN77800007 PM 8375239 ER PT J AU HARRIS, MI COWIE, CC HOWIE, LJ AF HARRIS, MI COWIE, CC HOWIE, LJ TI SELF-MONITORING OF BLOOD-GLUCOSE BY ADULTS WITH DIABETES IN THE UNITED-STATES POPULATION SO DIABETES CARE LA English DT Article ID RETINOPATHY; ACCURACY; DIAGNOSIS; RISK; COMPLICATIONS; PREVALENCE; MELLITUS; AGE AB OBJECTIVE - To evaluate self-monitoring of blood glucose, which is considered an important practice for patients with diabetes. However, little is known about the frequency or determinants of this technique. RESEARCH DESIGN AND METHODS - A detailed questionnaire on diabetes was administered to a representative sample of 2405 diabetic subjects greater-than-or-equal-to 18 yr of age in the U.S. population in the 1989 National Health Interview Survey. RESULTS- Among subjects with IDDM, 40% monitored their blood glucose at least 1 time/day. Among subjects with NIDDM treated with insulin, 26% monitored at least 1 time/day and among NIDDM subjects not treated with insulin, the percentage was 5%. When stratified by age, little difference was observed between IDDM subjects and insulin-treated NIDDM subjects in the percentage testing at least 1 time/day. By multivariate analysis, age and insulin use were the major determinants of whether diabetic subjects tested their blood glucose. Race and education were also independently related to self-monitoring of blood glucose. Blacks were 60% less likely to test their blood glucose at least 1 time/day compared with non-Hispanic whites and Mexican Americans. Those with college educations were 80% more likely to test their blood glucose compared with those with lower education levels. Having had a patient education class in diabetes management and frequent physician visits for diabetes care were positively related to self-testing. Self-monitoring was not related to higher income or having health insurance. CONCLUSIONS- A large proportion of patients with diabetes do not test their blood glucose. Financial barriers associated with income and health insurance do not appear to impede the practice of self-monitoring. Because of the importance of blood glucose control in the prevention of diabetes complications and the role of self-monitoring in achieving blood glucose control, it may be prudent for physicians and their patients to make greater use of this technique. Special attention should be directed to the subgroups of patients (blacks, patients not treated with insulin, those with less education, and those with no education in diabetes) in which the frequency of self-monitoring is particularly low. C1 SOCIAL & SCI SYST INC,BETHESDA,MD. NATL CTR HLTH STAT,HYATTSVILLE,MD 20782. RP HARRIS, MI (reprint author), NIDDKD,NATL DIABET DATA GRP,WESTWOOD BLDG,ROOM 620,BETHESDA,MD 20892, USA. NR 35 TC 111 Z9 118 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD AUG PY 1993 VL 16 IS 8 BP 1116 EP 1123 DI 10.2337/diacare.16.8.1116 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LN778 UT WOS:A1993LN77800009 PM 8375241 ER PT J AU EGAN, JM PERFETTI, R AF EGAN, JM PERFETTI, R TI THE EFFECTS OF AGING ON INSULIN RELEASE AND INSULIN MESSAGE IN RATS SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIA,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1993 VL 36 SU 1 BP A118 EP A118 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LZ274 UT WOS:A1993LZ27400446 ER PT J AU KADOR, PF TAKAHASHI, Y FERRIS, F WYMAN, M AF KADOR, PF TAKAHASHI, Y FERRIS, F WYMAN, M TI DIABETES-LIKE PROLIFERATIVE RETINAL CHANGES IN GALACTOSE-FED DOGS SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1993 VL 36 SU 1 BP A191 EP A191 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LZ274 UT WOS:A1993LZ27400725 ER PT J AU NARAYAN, KMV HANSON, RL KNOWLER, WC PETTITT, DJ AF NARAYAN, KMV HANSON, RL KNOWLER, WC PETTITT, DJ TI GLYCOSYLATED HEMOGLOBIN CAN IDENTIFY SUBJECTS AT HIGH-RISK FOR TYPE-2 DIABETES SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIDDKD,PHOENIX,AZ 85014. RI Narayan, K.M. Venkat /J-9819-2012 OI Narayan, K.M. Venkat /0000-0001-8621-5405 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1993 VL 36 SU 1 BP A159 EP A159 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LZ274 UT WOS:A1993LZ27400602 ER PT J AU NELSON, RG BECK, GJ BENNETT, PH KNOWLER, WC MITCH, WE AF NELSON, RG BECK, GJ BENNETT, PH KNOWLER, WC MITCH, WE TI CHANGES IN GLOMERULAR FUNCTION WITH THE ONSET OF NON-INSULIN-DEPENDENT DIABETES IN PIMA-INDIANS SO DIABETOLOGIA LA English DT Meeting Abstract C1 STANFORD UNIV,PALO ALTO,CA 94304. EMORY UNIV,ATLANTA,GA 30322. CLEVELAND CLIN EDUC FDN,NIDDK,CLEVELAND,OH 44106. DIABET RENAL DIS STUDY GRP,PHOENIX,AZ. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1993 VL 36 SU 1 BP A27 EP A27 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LZ274 UT WOS:A1993LZ27400096 ER PT J AU NYOMBA, BL MOTT, DM AF NYOMBA, BL MOTT, DM TI CORRELATION OF INSULIN ACTION WITH TYPE-1 PROTEIN PHOSPHATASE GLYCOGEN-BINDING SUBUNIT IN HUMANS SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIH,PHOENIX,AZ. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1993 VL 36 SU 1 BP A124 EP A124 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LZ274 UT WOS:A1993LZ27400471 ER PT J AU PERFETTI, R EGAN, JM ZENILMAN, ME SHULDINER, AR AF PERFETTI, R EGAN, JM ZENILMAN, ME SHULDINER, AR TI CLONING AND EXPRESSION OF THE MOUSE PANCREATIC REGENERATING (REG) GENE SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIA,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1993 VL 36 SU 1 BP A6 EP A6 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LZ274 UT WOS:A1993LZ27400016 ER PT J AU PETTITT, DJ NARAYAN, KMV HANSON, RL NAGI, DK MCCANCE, DR JACOBSSON, LTH KNOWLER, WC AF PETTITT, DJ NARAYAN, KMV HANSON, RL NAGI, DK MCCANCE, DR JACOBSSON, LTH KNOWLER, WC TI WORLD-HEALTH-ORGANIZATION AND NATIONAL-DIABETES-DATA-GROUP CRITERIA DURING PREGNANCY SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIDDKD,PHOENIX,AZ 85014. RI Narayan, K.M. Venkat /J-9819-2012 OI Narayan, K.M. Venkat /0000-0001-8621-5405 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1993 VL 36 SU 1 BP A55 EP A55 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LZ274 UT WOS:A1993LZ27400205 ER PT J AU SPRAUL, M ANDERSON, EA RAVUSSIN, E AF SPRAUL, M ANDERSON, EA RAVUSSIN, E TI MUSCLE SYMPATHETIC-NERVE ACTIVITY IN RESPONSE TO GLUCOSE-INGESTION - EFFECT OF INSULIN AND BODY-FAT SO DIABETOLOGIA LA English DT Meeting Abstract C1 UNIV IOWA,IOWA CITY,IA 52242. NIDDK,PHOENIX,AZ. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1993 VL 36 SU 1 BP A162 EP A162 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LZ274 UT WOS:A1993LZ27400614 ER PT J AU YKIJARVINEN, H LINDSTROM, J MOTT, D AF YKIJARVINEN, H LINDSTROM, J MOTT, D TI RESTORATION OF NORMOGLYCEMIA BY INSULIN THERAPY REVERSES DEFECTS IN INSULIN ACTIVATION OF SKELETAL-MUSCLE PROTEIN PHOSPHATASE-1 (PP1) AND GLYCOGEN-SYNTHASE (GS) IN TYPE-2 DIABETES (DM) SO DIABETOLOGIA LA English DT Meeting Abstract C1 NIDDK,PHOENIX,AZ. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 1993 VL 36 SU 1 BP A123 EP A123 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LZ274 UT WOS:A1993LZ27400466 ER PT J AU BERENGUER, J BUCK, M WITEBSKY, F STOCK, F PIZZO, PA WALSH, TJ AF BERENGUER, J BUCK, M WITEBSKY, F STOCK, F PIZZO, PA WALSH, TJ TI LYSIS CENTRIFUGATION BLOOD CULTURES IN THE DETECTION OF TISSUE-PROVEN INVASIVE CANDIDIASIS - DISSEMINATED VERSUS SINGLE-ORGAN INFECTION SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article ID TROPICALIS; RECOVERY; FUNGEMIA; SYSTEMS; YEASTS AB Several studies have demonstrated significantly higher frequency and more rapid detection of candidemia with blood culture methods performed by lysis-centrifugation (LC) in comparison with other techniques. Little is known, however, about the ability of LC blood culture methods to detect tissue-proven invasive candidiasis. We therefore investigated the sensitivity of LC blood cultures in the detection of tissue-proven invasive candidiasis. Between 1985 and 1991, invasive candidiasis was detected in 41 (5.1%) of 803 autopsies at the Clinical Center of the National Institutes of Health (Bethesda, MD, USA). Cases were classified as single-organ (SO) candidiasis (n = 20) and as disseminated candidiasis (DI) (n = 21). Patients with DI were more likely than those with SO to have a hematologic malignancy (71% vs 15%, P < 0.001) and to have gastrointestinal mucosal candidiasis (76% vs 25%, P = 0.003). LC detected fungemia in 16 (43%) of all 37 cases with blood cultures. When analyzed by classification, Candida spp. were isolated from blood in 11 (58%) of 19 patients with DI and in five (28%) of 18 patients with SO (P = 0.13). When analyzed by number of organs infected, blood cultures were positive in seven (78%) of nine patients with > 3 organs infected by Candida in comparison ta five (28%) of 18 patients with one organ infected (P = 0.024). The mean recovery time for Candida in blood cultures was 2.6 days in DI and 3.2 days in SO (P = 0.017). There was no difference in colonies of organisms per LC tube between patients with DI and those with SO. These findings indicate that LC blood cultures are more likely to detect deeply invasive candidiasis in direct relation to the number of tissue sites infected and that there is a critical need for development of more sensitive methods for detection of invasive candidiasis. C1 NCI,INFECT DIS SECT,PEDIAT BRANCH,BLDG 10,ROOM 13N-240,BETHESDA,MD 20892. NCI,DEPT PATHOL,BETHESDA,MD 20892. WARREN GRANT MAGNUSON CLIN CTR,DEPT CLIN PATHOL,MICROBIOL SERV,BETHESDA,MD. OI Berenguer, Juan/0000-0001-8541-8200 NR 21 TC 165 Z9 169 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD AUG-SEP PY 1993 VL 17 IS 2 BP 103 EP 109 DI 10.1016/0732-8893(93)90020-8 PG 7 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA LY535 UT WOS:A1993LY53500003 PM 8243032 ER PT J AU JI, XD GALLORODRIGUEZ, C JACOBSON, KA AF JI, XD GALLORODRIGUEZ, C JACOBSON, KA TI 8-(3-ISOTHIOCYANATOSTYRYL)CAFFEINE IS A SELECTIVE, IRREVERSIBLE INHIBITOR OF STRIATAL A(2)-ADENOSINE RECEPTORS SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE XANTHINES; AFFINITY LABEL; ADENOSINE RECEPTORS; RADIOLIGAND BINDING ID ADENOSINE-A2 RECEPTOR; BINDING-SITES; BRAIN; MEMBRANES; LIGAND; CELLS AB 8-(3-Isothiocyanatostyryl)caffeine (ISC) was synthesized and shown to inhibit selectively the binding of [H-3]CGS 21680 (an A2a-selective agonist) at adenosine receptors in striatal membranes. The K(i) value at A2a-receptors was found to be 110 nM (rat), with selectivity ratios for A2a versus A1-receptors in rat, guinea pig, bovine, and rabbit striatum of >100-fold. Preincubation of membranes with ISC caused a dose-dependent, irreversible antagonism of the binding of [H-3]CGS 21680, with an IC50 value of 3 muM. The irreversibility is likely due to the presence of the chemically reactive isothiocyanate group, since the binding of the corresponding analogue in which the isothiocyanate was replaced with a chloro group was completely reversible. The potency of ISC to irreversibly inhibit the binding of [H-3]CGS 21680 in several species varied in the order rat almost-equal-to guinea pig > bovine almost-equal-to rabbit. In all four species, binding of the A1-selective agonist [H-3]R-N6-phenylisopropyladenosine was not diminished by pre-treatment with 2 muM ISC. The kinetics of irreversible inhibition of rat A2a-receptors by 2 muM ISC gave a t1/2 of approximately 3 min. Following partial inactivation, the remaining rat A2a-binding sites retained the same K(d) value as in control membranes for saturation by [H-3]CGS 21680. Thus, ISC appears to be a selective affinity label for A2a-versus A1-receptors in the brain. (C) 1993 Wiley-Liss, Inc.* C1 NIDDKD,BIOORGAN CHEM LAB,BLDG 8A,RM B1A-17,BETHESDA,MD 20892. RI Gallo-Rodriguez, Carola/E-1732-2012; Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [ZIA DK031117-22, Z99 DK999999] NR 24 TC 4 Z9 4 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD AUG PY 1993 VL 29 IS 4 BP 292 EP 298 DI 10.1002/ddr.430290407 PG 7 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LR641 UT WOS:A1993LR64100006 PM 22787287 ER PT J AU PROTIC, M LEVINE, AS AF PROTIC, M LEVINE, AS TI DETECTION OF DNA DAMAGE-RECOGNITION PROTEINS USING THE BAND-SHIFT ASSAY AND SOUTHWESTERN HYBRIDIZATION SO ELECTROPHORESIS LA English DT Article ID COMPLEMENTATION GROUP-E; XERODERMA PIGMENTOSUM-CELLS; NUCLEOTIDE EXCISION REPAIR; ANTICANCER DRUG CISPLATIN; ESCHERICHIA-COLI UVRA; BINDING-PROTEIN; GEL-ELECTROPHORESIS; HELA-CELLS; MOLECULAR-CLONING; YEAST PHOTOLYASE AB We describe electrophoresis and biochemical conditions that allow detection of damaged DNA-binding proteins in cell extracts. In addition, we present an overview of the damage-recognition DNA-binding proteins from eukaryotic cells and discuss their hypothetical role in DNA repair. C1 NICHHD,DNA REPLICAT REPAIR & MUTAGENESIS,BETHESDA,MD 20892. NR 62 TC 16 Z9 16 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 AUG PY 1993 VL 14 IS 8 BP 682 EP 692 DI 10.1002/elps.11501401109 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA LW248 UT WOS:A1993LW24800004 PM 8404810 ER PT J AU ORBAN, L GARNER, MM WHEELER, D TIETZ, D CHRAMBACH, A AF ORBAN, L GARNER, MM WHEELER, D TIETZ, D CHRAMBACH, A TI CHARACTERIZATION OF THE ELECTROPHORETIC PROPERTIES OF NUCLEOSOME CORE PARTICLES BY TRANSVERSE POLYACRYLAMIDE PORE GRADIENT GEL-ELECTROPHORESIS SO ELECTROPHORESIS LA English DT Article ID CAPILLARY ELECTROPHORESIS; FERGUSON PLOTS; DNA; INFORMATION; COMPUTERS; MOBILITY AB Transverse pore gradient gel electrophoresis, previously applied to bent DNA, has extended the usefulness of the gel retardation assay in two ways: (i) by differentiating between different DNA conformations; (ii) by providing information regarding the physical properties of DNA. In the present study, similarly extended information is obtained with regard to a well-characterized DNA-protein complex, the chicken erythrocyte nucleosome core particle. (i) The winding of DNA around the protein core constrains the DNA which renders its Ferguson curve (migration distance vs. gel concentration) similar to that of kinetoplast DNA, i.e. it intersects sharply with the Ferguson curves of linear DNA standards. By contrast, the deproteinized nucleosome DNA exhibits a Ferguson curve similar to linear standards of the same lenght. (ii) Interpretation of the Ferguson curve based on a mathematical model shows that the nucleosome exhibits a linear Ferguson plot [log(mobility) vs. gel concentration]. This is similar to and characteristic of spherical proteins, contrasting with the concave plot typical for linear and bent DNA. (iii) The effective size of the nucleosome, evaluated in terms of an ''equivalent sphere'' (i.e. a hypothetical spherical particle with a radius, R(es), having the same electrophoretic mobility as DNA for a particular set of experimental conditions), remains invariant across the gel concentration range of 3-9%T. This is similar to proteins and bacteriophages and contrasts with the progressive decline of R(es) with increasing gel concentration observed for linear DNA and the deproteinized nucleosomal DNA. C1 AGR BIOTECHNOL CTR,INST MOLEC GENET,GODOLLO,HUNGARY. NICHHD,MACROMOLEC ANAL SECT,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892. OI Orban, Laszlo/0000-0001-5435-5948 NR 22 TC 16 Z9 16 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 AUG PY 1993 VL 14 IS 8 BP 720 EP 724 DI 10.1002/elps.11501401114 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA LW248 UT WOS:A1993LW24800009 PM 8404815 ER PT J AU HOWCROFT, TK RICHARDSON, JC SINGER, DS AF HOWCROFT, TK RICHARDSON, JC SINGER, DS TI MHC CLASS-I GENE-EXPRESSION IS NEGATIVELY REGULATED BY THE PROTOONCOGENE, C-JUN SO EMBO JOURNAL LA English DT Article DE AP-1; C-JUN; GENE EXPRESSION; MHC CLASS-I; ONCOGENE ID MAJOR HISTOCOMPATIBILITY COMPLEX; MESSENGER-RNA LEVELS; TRANSCRIPTIONAL ACTIVATION; RESPONSE ELEMENT; CELLS; ANTIGENS; MOUSE; FOS; PROTEINS; INTERFERON AB The trans-acting factor AP-1 is a heterodimeric complex composed of c-Jun and c-Fos family proteins which bind and regulate genes containing a TPA responsive enhancer element. Although AP-1 binding sites have been identified within the regulatory region of major histocompatibility complex (MHC) class I genes in vitro, the role of AP-1 in regulating MHC class I transcription in vivo has not been investigated previously. The present study demonstrates that expression of c-Jun results in decreased MHC class I promoter activity as determined in cotransfection assays of an MHC class I reporter construct with a c-Jun expression construct. The c-Jun responsive element is located between bp -440 and -431 upstream of initiation of transcription as determined both functionally and by direct binding of purified c-Jun. Furthermore, over-expression of c-Jun reduced the steady state levels of endogenous MHC class I RNA in murine L cells by approximately 10-fold. These data indicate that c-Jun/AP-1 acts as a negative trans-acting factor that down-regulates MHC class I gene expression. RP HOWCROFT, TK (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B-17,BETHESDA,MD 20892, USA. NR 55 TC 54 Z9 54 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD AUG PY 1993 VL 12 IS 8 BP 3163 EP 3169 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LP429 UT WOS:A1993LP42900019 PM 8344255 ER PT J AU ENGELMAN, A BUSHMAN, FD CRAIGIE, R AF ENGELMAN, A BUSHMAN, FD CRAIGIE, R TI IDENTIFICATION OF DISCRETE FUNCTIONAL DOMAINS OF HIV-1 INTEGRASE AND THEIR ORGANIZATION WITHIN AN ACTIVE MULTIMERIC COMPLEX SO EMBO JOURNAL LA English DT Article DE ACQUIRED IMMUNE DEFICIENCY SYNDROME; DNA RECOMBINATION; HUMAN IMMUNODEFICIENCY VIRUS; INTEGRATION; MULTIMERIC COMPLEX ID HUMAN-IMMUNODEFICIENCY-VIRUS; RETROVIRAL DNA INTEGRATION; PROTEIN INVITRO; MU-TRANSPOSITION; TYPE-1; CLEAVAGE; BINDING; RECOMBINATION; RECOGNITION; SEQUENCES AB HIV-1 integrase protein possesses the 3' processing and DNA strand transfer activities that are required to integrate HIV DNA into a host chromosome. The N-, C-terminal and core domains of integrase are necessary for both activities in vitro. We rind that certain pairs of mutant integrase proteins, which are inactive when each protein is assayed alone, can support near wild type levels of activity when both proteins are present together in the reaction mixture. This complementation implies that HIV-1 integrase functions as a multimer and has enabled us to probe the organization of the functional domains within active mixed multimers. We have identified a minimal set of functional integrase domains that are sufficient for 3' processing and DNA strand transfer and find that some domains are contributed in trans by separate monomers within the functional complex. RP NIDDKD, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. NR 39 TC 292 Z9 299 U1 0 U2 3 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 AUG PY 1993 VL 12 IS 8 BP 3269 EP 3275 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LP429 UT WOS:A1993LP42900030 PM 8344264 ER PT J AU YOUNG, WS KOVACS, K LOLAIT, SJ AF YOUNG, WS KOVACS, K LOLAIT, SJ TI THE DIURNAL RHYTHM IN VASOPRESSIN V1A RECEPTOR EXPRESSION IN THE SUPRACHIASMATIC NUCLEUS IS NOT DEPENDENT ON VASOPRESSIN SO ENDOCRINOLOGY LA English DT Article ID VASOACTIVE INTESTINAL PEPTIDE; INSITU HYBRIDIZATION HISTOCHEMISTRY; MESSENGER-RNA; RAT-BRAIN; BRATTLEBORO RATS; BINDING-SITES; HYPOTHALAMIC NUCLEI; OXYTOCIN; LOCALIZATION; SYSTEM AB The mammalian suprachiasmatic nucleus is the site of the circadian rhythm generator. The degrees of expression there of several neuropeptides, including vasopressin and vasoactive intestinal polypeptide, follow a diurnal rhythm. The vasopressin V1a receptor, whose activation results in phosphoinositol hydrolysis and mobilization of intracellular calcium, is expressed in this nucleus. This study used double simultaneous hybridization histochemistry to show that V1a receptor transcripts are present in both vasopressin and vasoactive intestinal polypeptide neurons and that their levels follow a diurnal rhythm. Furthermore, the expression of the V1a receptor is 12 h out of phase from that of vasopressin. However, the receptor's diurnal rhythm is still maintained in the vasopressin-deficient Brattleboro rat, indicating that the Via receptor's rhythm is independent of any vasopressin feedback. C1 HUNGARIAN ACAD SCI, INST EXPTL MED, H-1361 BUDAPEST 5, HUNGARY. RP YOUNG, WS (reprint author), NIMH, CELL BIOL LAB, BLDG 36, ROOM 2010, BETHESDA, MD 20892 USA. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 NR 41 TC 55 Z9 56 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 1993 VL 133 IS 2 BP 585 EP 590 DI 10.1210/en.133.2.585 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LQ846 UT WOS:A1993LQ84600024 PM 8344200 ER PT J AU DOMENE, H KRISHNAMURTHI, K ESHET, R GILAD, I LARON, Z KOCH, I STANNARD, B CASSORLA, F ROBERTS, CT LEROITH, D AF DOMENE, H KRISHNAMURTHI, K ESHET, R GILAD, I LARON, Z KOCH, I STANNARD, B CASSORLA, F ROBERTS, CT LEROITH, D TI GROWTH-HORMONE (GH) STIMULATES INSULIN-LIKE GROWTH FACTOR-I (IGF-I) AND IGF-I-BINDING PROTEIN-3, BUT NOT GH RECEPTOR GENE-EXPRESSION IN LIVERS OF JUVENILE RATS SO ENDOCRINOLOGY LA English DT Article ID MESSENGER-RNAS; DEVELOPMENTAL REGULATION; RIBONUCLEIC-ACID; TRANSCRIPTION; SOMATOSTATIN; MICE AB In the adult rat, expression of the liver GH receptor, insulin-like growth factor-I (IGF-I), and IGF-I-binding protein-3 (IGFBP-3) genes has been shown to be under GH control. Additionally, hypophysectomy and GH treatment have a differential effect on the relative abundance of liver IGF-I mRNA variants in adult rats. To further elucidate the time of appearance and the extent of GH control of liver GH receptor, IGF-I, and IGFBP-3 gene expression, we studied the effect of hypophysectomy and GH and IGF-I treatment in juvenile rats. Male Wistar rats were hypophysectomized (Hx) on postnatal day 26 and received twice daily sc injections of saline, recombinant human GH (2.5 U/kg. day), or recombinant human IGF-I (500 mug/kg.day) for 7 days. Sham-operated rats received the same treatment. Hx animals also received T4 (20 mug/kg.day). In Hx animals, there was a significant reduction in body weight (69.8 +/- 6.6 vs. 100.4 +/- 5.4 g; P < 0.001). GH, but not IGF-I, treatment increased body weight (79.6 +/- 9.6 g after GH vs. 69.8 +/-6.6 g before GH; P < 0.05). GH treatment partially maintained liver, kidney, and lung weights in Hx animals and increased them in intact animals, whereas IGF-I treatment did so only in the lungs of intact and Hx animals. Serum GH and IGF-I levels were markedly reduced in Hx animals compared with those in intact controls, and GH treatment maintained, albeit partially, circulating IGF-I levels compared with those in saline-treated Hx animals. IGF-I mRNA levels were markedly reduced in Hx liver (25.0 +/- 5.4%; P < 0.001 compared with intact controls). GH treatment for 7 days increased IGF-I mRNA levels by 4.8-fold over the levels in 9-day Hx animals and increased IGF-I mRNA levels by 2.2-fold in control rats. Hypophysectomy decreased exon 2-containing transcripts by 7.0-fold and exon 1-containing transcripts by 4.1-fold. GH treatment, however, affected both exon 1- and exon 2-containing transcripts similarly. Hepatic IGFBP-3 mRNA levels were reduced in Hx (53.2 +/- 1.8%; P < 0.01 compared with intact controls) and IGF-treated Hx animals, but were not decreased in Hx GH-treated animals (100.6 +/- 9.5). No changes in GH receptor or GH-binding protein mRNA levels were caused by Hx, GH, or IGF-I treatment. These findings suggest that in juvenile rats, the IGF-I, IGFBP-3, and GH receptor/GH-binding protein genes are differentially sensitive to GH. Whereas IGF-I gene expression is extremely sensitive to changes in circulating GH levels, IGFBP-3 mRNA appears to be less sensitive to GH, and GH receptor/GH-binding protein mRNA levels appear to be GH independent. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. CHILDRENS MED CTR ISRAEL, INST PEDIAT & ADOLESCENT ENDOCRINOL, DEPT PEDIAT ENDOCRINOL & DIABET RES, PETAH TIQWA, ISRAEL. TEL AVIV UNIV, SACKLER FAC MED, IL-69978 TEL AVIV, ISRAEL. WEIZMANN INST SCI, DEPT HORMONE RES, IL-76100 REHOVOT, ISRAEL. OI Roberts, Charles/0000-0003-1756-5772 NR 28 TC 58 Z9 58 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 1993 VL 133 IS 2 BP 675 EP 682 DI 10.1210/en.133.2.675 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LQ846 UT WOS:A1993LQ84600036 PM 7688291 ER PT J AU SELTZER, A TSUTSUMI, K SHIGEMATSU, K SAAVEDRA, JM AF SELTZER, A TSUTSUMI, K SHIGEMATSU, K SAAVEDRA, JM TI REPRODUCTIVE HORMONES MODULATE ANGIOTENSIN-II AT1 RECEPTORS IN THE DORSOMEDIAL ARCUATE NUCLEUS OF THE FEMALE RAT SO ENDOCRINOLOGY LA English DT Note ID PROLACTIN SECRETION; TYROSINE-HYDROXYLASE; LUTEINIZING-HORMONE; MEDIAN-EMINENCE; BRAIN; DOPAMINE; PROGESTERONE; AUTORADIOGRAPHY; COLOCALIZATION; HYPOTHALAMUS AB Angiotensin II AT1 receptors are highly localized in the dorsomedial arcuate nucleus. AT1 receptor number is very low during proestrus and in ovariectomized and male rats, and is high only during the estrus phase of the estrous cycle and after ovariectomized rats receive a sequential estrogen-progesterone treatment. Our results suggest that the mechanism of the estrogen-progesterone inhibition of the prolactin surge may involve the selective stimulation of dorsomedial arcuate AT1 receptors. C1 NIMH, CLIN SCI LAB,PHARMACOL SECT,BLDG 10,ROOM 20-45, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 16 TC 25 Z9 25 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 1993 VL 133 IS 2 BP 939 EP 941 DI 10.1210/en.133.2.939 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LQ846 UT WOS:A1993LQ84600070 PM 8344227 ER PT J AU NEWBOLD, RR AF NEWBOLD, RR TI GENDER-RELATED BEHAVIOR IN WOMEN EXPOSED PRENATALLY TO DIETHYLSTILBESTROL SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID CLEAR-CELL ADENOCARCINOMA; GENITAL-TRACT ABNORMALITIES; SEXUALLY DIMORPHIC NUCLEUS; FEMALE GUINEA-PIG; HUMAN-BRAIN; SEX-DIFFERENCES; PSYCHOSEXUAL DEVELOPMENT; POSTNATAL INFLUENCE; DES; DIFFERENTIATION AB Accumulating evidence in experimental animals over the past three decades suggests that mammalian brain development and differentiation of the central nervous system are influenced by perinatal exposure to sex hormones. Hence, changes in human behavioral patterns may be associated with prenatal exposure to estrogenic substances such as diethylstilbestrol (DES). This paper reviews relevant studies from a series of laboratories and finds that no clear-cut differences can be demonstrated to date between unexposed and DES-exposed women in gender-related behavior, although the physical and psychological impact of the problems associated with exposure to DES are well documented. If both prenatal and postnatal influences such as social, economic, and environmental factors are taken into consideration, individual variation is more apparent than differences in gender-related behavior between unexposed and DES-exposed women. In summary, gender-related behavior is determined by a complex array of interacting factors, and prenatal influences are only one of many developmental events. More studies are needed using larger populations with carefully controlled selection criteria to suggest a direct role of prenatal DES exposure on subsequent gender-related behavior. RP NEWBOLD, RR (reprint author), NIEHS,E4-04,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 68 TC 13 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 AUG PY 1993 VL 101 IS 3 BP 208 EP 213 DI 10.2307/3431541 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA MF161 UT WOS:A1993MF16100002 PM 8404755 ER PT J AU YORK, DM DARDEN, TA PEDERSEN, LG ANDERSON, MW AF YORK, DM DARDEN, TA PEDERSEN, LG ANDERSON, MW TI MOLECULAR MODELING STUDIES SUGGEST THAT ZINC IONS INHIBIT HIV-1 PROTEASE BY BINDING AT CATALYTIC ASPARTATES SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 PROTEASE; CRYSTAL-STRUCTURE; NUCLEIC-ACIDS; FORCE-FIELD; RESOLUTION; COMPLEX; PROTEINASE; POLYMERASE; SIMULATION AB Human immunodeficiency vims type 1 protease is inhibited in vitro by zinc ions at neutral pH. The binding site of these ions is not known; however, experimental data suggest that binding may occur in the active site. To examine the possibility of zinc binding in the active site, molecular dynamics simulations in the presence and absence of zinc have been carried out to 200 psec. The results are compared with the 2.8-A crystallographic structure of a synthetic HIV-1 protease, and a zinc binding site at the catalytic aspartate residues (Asp-25, Asp-25') is proposed. Molecular dynamics simulations show that the zinc ion remains stably bound in this region, coordinating the carboxylate side chains of both aspartate residues. Interaction with zinc does not disrupt the dimeric structure of the protein or significantly alter the structure of the active site. These data are consistent with experimental studies of HIV-1 protease inhibition by zinc and give strong evidence that this is the binding site that leads to inactivation. C1 UNIV N CAROLINA,DEPT CHEM,CHAPEL HILL,NC 27599. RP YORK, DM (reprint author), NIEHS,MOLEC TOXICOL LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 FU NHLBI NIH HHS [HL27995] NR 38 TC 5 Z9 5 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 AUG PY 1993 VL 101 IS 3 BP 246 EP 250 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA MF161 UT WOS:A1993MF16100008 PM 8404763 ER PT J AU KLINMAN, DM HOLMES, KL CONOVER, J CHIANG, BL GERSHWIN, ME AF KLINMAN, DM HOLMES, KL CONOVER, J CHIANG, BL GERSHWIN, ME TI B-1A AND CONVENTIONAL B-CELLS FROM AUTOIMMUNE NZB.H-2BM12 MICE EXHIBIT SIMILAR FUNCTIONAL-CHARACTERISTICS IN-VIVO SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE B-1 CELLS; LY-1 CELLS; IMMUNOGLOBULIN ISOTYPE; AUTOIMMUNITY; LUPUS ID SYSTEMIC LUPUS-ERYTHEMATOSUS; T-HELPER CELLS; LY-1 B; ANTIBODY-PRODUCTION; RHEUMATOID-FACTOR; VIABLE MOTHEATEN; CROSS-REACTIVITY; MURINE MODELS; CD5+; AUTOANTIBODIES AB NZB.H-2bm12 mice develop an autoimmune syndrome characterized by the overproduction of anti-DNA antibodies and the expansion of B-1B cells. Thus, these animals provide a useful model to examine the antigenic specificity, cross-reactivity and functional capability of B-1 versus conventional lymphocytes. Neither the repertoire expressed by in vivo activated Ly-1+ splenic lymphocytes, nor their cross-reactivity, differed significantly from that of conventional splenic B cells. When Ly-1+ cells were cultured in vitro in the presence of lipopolysaccharide plus interleukin-4 or interferon gamma, they underwent isotype switching at the same frequency as conventional B cells. Of interest, B-1 cells from the peritoneal cavity were significantly less likely to undergo isotype switching than those from the spleen. These findings indicate that in vivo activated B-1a and conventional B cells from mice with lupus manifest similar functional characteristics. C1 CBER,FDA,DIV VIROL,FLOW CYTOMETRY SECT,BETHESDA,MD 20892. NIAID,BIOL RESOURCES BRANCH,BETHESDA,MD 20892. UNIV CALIF DAVIS,DIV RHEUMATOL ALLERGY,DAVIS,CA 95616. RP KLINMAN, DM (reprint author), CBER,FDA,RETROVIRAL IMMUNOL SECT,BLDG 29A,RM 3 D10,BETHESDA,MD 20892, USA. OI CHIANG, BOR-LUEN/0000-0002-6705-0286 FU NCI NIH HHS [CA 20816] NR 46 TC 7 Z9 7 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD AUG PY 1993 VL 23 IS 8 BP 1866 EP 1871 DI 10.1002/eji.1830230820 PG 6 WC Immunology SC Immunology GA LT241 UT WOS:A1993LT24100019 PM 7688308 ER PT J AU WILLIAMS, ME KULLBERG, MC BARBIERI, S CASPAR, P BERZOFSKY, JA SEDER, RA SHER, A AF WILLIAMS, ME KULLBERG, MC BARBIERI, S CASPAR, P BERZOFSKY, JA SEDER, RA SHER, A TI FC-EPSILON RECEPTOR-POSITIVE CELLS ARE A MAJOR SOURCE OF ANTIGEN-INDUCED INTERLEUKIN-4 IN SPLEENS OF MICE INFECTED WITH SCHISTOSOMA-MANSONI SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE SCHISTOSOMA-MANSONI; CYTOKINES; INTERLEUKIN-4; FC-EPSILON RECEPTOR ID NON-T CELLS; CROSS-LINKAGE; NON-B; PRODUCE INTERLEUKIN-4; MONOCLONAL-ANTIBODY; PROTECTIVE IMMUNITY; CYTOKINE PRODUCTION; PARASITE ANTIGEN; IL-4; IDENTIFICATION AB When cultured in vitro with either mitogen or parasite antigens, spleen cells from mice infected with Schistosoma mansoni produce significantly higher levels of IL-4 than splenocytes from control animals. Previous studies suggested that this increase in IL-4 production occurs because of a selective expansion of T helper type 2 (Th2) cells in infected mice. However, these experiments employed unfractionated spleen populations rather than purified T lymphocytes. Here we demonstrate that T-depleted spleen cells from infected animals synthesize high levels of interleukin-4 (IL-4), but no IL-5 when stimulated with parasite antigen in vitro. Nevertheless, when purified by sorting, T cells and non-B, non-T (NBNT) populations produced similar amounts of IL-4 in response to parasite antigen. The IL-4 producing NBNT cells were found to belong to an Fcepsilon receptor (FcepsilonR)-positive population which after sort purification produced high levels of IL-4 (between 1000 and 2000 U of per 5 X 10(3) cells). FACS analysis revealed that these FcepsilonR+ cells make up 0.53% of splenic NBNT cells in control animals while in 8-9-week-infected animals they increase to 3.8% of that population. In contrast, in mice with 8-week unisexual worm infections these cells comprise only 1.71% of NBNT cells, indicating that eggs are a major stimulus of the response. The expansion of FcepsilonR+ cells and their production of IL-4 could be an important factor regulating the selection and induction of different CD4+ subsets in schistosome-infected hosts. C1 NCI,IMMUNOL & CELL BIOL SECT,BETHESDA,MD 20892. NCI,PARASIT DIS LAB,MOLEC IMMUNOGENET & VACCINE RES SECT,BETHESDA,MD 20892. NCI,METAB BRANCH,BETHESDA,MD 20892. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. NIAID,BIOL RES BRANCH,BETHESDA,MD 20892. NR 33 TC 57 Z9 57 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD AUG PY 1993 VL 23 IS 8 BP 1910 EP 1916 DI 10.1002/eji.1830230827 PG 7 WC Immunology SC Immunology GA LT241 UT WOS:A1993LT24100026 PM 8344353 ER PT J AU BERTRAND, R SOLARY, E JENKINS, J POMMIER, Y AF BERTRAND, R SOLARY, E JENKINS, J POMMIER, Y TI APOPTOSIS AND ITS MODULATION IN HUMAN PROMYELOCYTIC HL-60 CELLS TREATED WITH DNA TOPOISOMERASE-I AND TOPOISOMERASE-II INHIBITORS SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID CALCIUM-DEPENDENT ENDONUCLEASE; PROTEIN-KINASE-C; RAT-LIVER NUCLEI; POLY(ADP-RIBOSE) SYNTHESIS; LEUKEMIA-CELLS; CHROMATIN STRUCTURE; MEDIATED APOPTOSIS; ANTICANCER DRUGS; INTERPHASE DEATH; THYMOCYTE NUCLEI C1 INST CANC MONTREAL,1560 SHERBROOKE E,MONTREAL H2L 4M1,PQ,CANADA. CHU BOCAGE,F-21000 DIJON,FRANCE. NCI,DCT,DTP,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NR 79 TC 127 Z9 129 U1 0 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD AUG PY 1993 VL 207 IS 2 BP 388 EP 397 DI 10.1006/excr.1993.1206 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA LP891 UT WOS:A1993LP89100022 PM 7688316 ER PT J AU SATO, S LIN, LR REDDY, VN KADOR, PF AF SATO, S LIN, LR REDDY, VN KADOR, PF TI ALDOSE REDUCTASE IN HUMAN RETINAL-PIGMENT EPITHELIAL-CELLS SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE RETINAL PIGMENT EPITHELIUM; HUMAN; ALDOSE REDUCTASE; ALDEHYDE REDUCTASE; PURIFICATION; ALDOSE REDUCTASE INHIBITORS ID DIABETIC COMPLICATIONS; ALDEHYDE REDUCTASE; GALACTOSEMIC RATS; MEDULLARY CELLS; POLYOL PATHWAY; MURAL CELLS; BB RAT; LOCALIZATION; INHIBITION; MYOINOSITOL C1 OAKLAND UNIV,EYE RES INST,ROCHESTER,MI 48063. RP SATO, S (reprint author), NEI,OCULAR THERAPEUT LAB,BLDG 10,ROOM 10M09,BETHESDA,MD 20892, USA. FU NEI NIH HHS [NEI EY05025, NEI EY00484] NR 38 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD AUG PY 1993 VL 57 IS 2 BP 235 EP 241 DI 10.1006/exer.1993.1119 PG 7 WC Ophthalmology SC Ophthalmology GA LT613 UT WOS:A1993LT61300013 PM 8405190 ER PT J AU FITZGERALD, D KREITMAN, RJ PASTAN, I AF FITZGERALD, D KREITMAN, RJ PASTAN, I TI RECOMBINANT IMMUNOTOXINS FOR CANCER-TREATMENT SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 NCI,DCBDC,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1993 VL 21 IS 8 BP 1012 EP 1012 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA MW613 UT WOS:A1993MW61300015 ER PT J AU MORGAN, RA RAGHEB, J VANDENDRIESSCHE, MC VANDENDRIESSCHE, T DETTENHOFER, M BRESSLER, P AF MORGAN, RA RAGHEB, J VANDENDRIESSCHE, MC VANDENDRIESSCHE, T DETTENHOFER, M BRESSLER, P TI PROGRESS TOWARDS GENE-THERAPY FOR AIDS SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892. NIAID,IMMUNOGENET LAB,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1993 VL 21 IS 8 BP 1012 EP 1012 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA MW613 UT WOS:A1993MW61300016 ER PT J AU LAWMAN, MJP KIRBY, MR LAWMAN, PD KESSLER, S DONAHUE, RE AF LAWMAN, MJP KIRBY, MR LAWMAN, PD KESSLER, S DONAHUE, RE TI STEM-CELL PROLIFERATION FACTOR (SCPF) - A NOVEL CYTOKINE CAPABLE OF PROLIFERATING CD34+ CELLS IN LONG-TERM CULTURE SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 UNIV FLORIDA,COLL MED,GAINESVILLE,FL 32611. NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. USN,MED RES INST,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1993 VL 21 IS 8 BP 1022 EP 1022 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA MW613 UT WOS:A1993MW61300048 ER PT J AU NAPARSTEK, E OR, R NAGLER, A CIVIDALLI, G ENGELHARD, D GIMON, Z MANNY, N WEISS, L SAMUEL, S BRAUTBAR, H HALE, G WALDMANN, H STEINBERG, S SLAVIN, S AF NAPARSTEK, E OR, R NAGLER, A CIVIDALLI, G ENGELHARD, D GIMON, Z MANNY, N WEISS, L SAMUEL, S BRAUTBAR, H HALE, G WALDMANN, H STEINBERG, S SLAVIN, S TI ALLOGENEIC BONE-MARROW TRANSPLANTATION FOR LEUKEMIA USING CAMPATH-1 MONOCLONAL-ANTIBODIES AND POSTTRANSPLANT ALLOIMMUNIZATION WITH DONOR LYMPHOCYTES SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 HADASSAH UNIV HOSP,JERUSALEM,ISRAEL. UNIV CAMBRIDGE,CAMBRIDGE,CAMBS,ENGLAND. NCI,BETHESDA,MD. NR 0 TC 4 Z9 4 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1993 VL 21 IS 8 BP 1061 EP 1061 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA MW613 UT WOS:A1993MW61300189 ER PT J AU MICKISCH, GHJ SCHROEDER, FH GOTTESMAN, MM PASTAN, I AF MICKISCH, GHJ SCHROEDER, FH GOTTESMAN, MM PASTAN, I TI MRK16-PE - AN IMMUNOCONJUGATE SPECIFIC FOR MULTIDRUG-RESISTANT CELLS SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 ERASMUS UNIV HOSP,ROTTERDAM,NETHERLANDS. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1993 VL 21 IS 8 BP 1079 EP 1079 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA MW613 UT WOS:A1993MW61300253 ER PT J AU ANAGNOSTOU, A LIU, Z STEINER, M CHIN, K LEE, ES NOGUCHI, CT AF ANAGNOSTOU, A LIU, Z STEINER, M CHIN, K LEE, ES NOGUCHI, CT TI ERYTHROPOIETIN RECEPTOR MESSENGER-RNA EXPRESSION IN HUMAN ENDOTHELIAL-CELLS SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 MEM HOSP RHODE ISL,PAWTUCKET,RI. BROWN UNIV,SCH MED,DIV HEMATOL ONCOL,PAWTUCKET,RI. NIDDK,CHEM BIOL LAB,BETHESDA,MD. NR 1 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1993 VL 21 IS 8 BP 1083 EP 1083 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA MW613 UT WOS:A1993MW61300267 ER PT J AU STEINER, M LEE, ES NOGUCHI, CT ANAGNOSTOU, A AF STEINER, M LEE, ES NOGUCHI, CT ANAGNOSTOU, A TI THE ERYTHROPOIETIN-INDUCED PROLIFERATION OF HUMAN ENDOTHELIAL-CELL IS ASSOCIATED WITH P34(CDC2) KINASE ACTIVATION SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 MEM HOSP RHODE ISL,PAWTUCKET,RI. BROWN UNIV,SCH MED,DIV HEMATOL ONCOL,PAWTUCKET,RI. NIDDK,CHEM & BIOL LAB,BETHESDA,MD. NR 1 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1993 VL 21 IS 8 BP 1083 EP 1083 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA MW613 UT WOS:A1993MW61300266 ER PT J AU ORLIC, D ANDERSON, S PIAO, X BERNSTEIN, A NIENHUIS, AW BODINE, DM AF ORLIC, D ANDERSON, S PIAO, X BERNSTEIN, A NIENHUIS, AW BODINE, DM TI MESSENGER-RNA EXPRESSION IN PURIFIED POPULATIONS OF MOUSE PLURIPOTENT HEMATOPOIETIC STEM-CELLS SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. MT SINAI HOSP,TORONTO,ON,CANADA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1993 VL 21 IS 8 BP 1114 EP 1114 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA MW613 UT WOS:A1993MW61300382 ER PT J AU DUBOIS, CM WANG, JM OPPENHEIM, JJ DAVIES, N NETA, R AF DUBOIS, CM WANG, JM OPPENHEIM, JJ DAVIES, N NETA, R TI IL-1 INCREASES C-KIT GENE AND CELL-SURFACE PROTEIN EXPRESSION - CORRELATION WITH PROTECTION FROM LETHAL IRRADIATION SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 UNIV SHERBROOKE,FAC MED,DIV IMMUNOL,SHERBROOKE J1K 2R1,PQ,CANADA. NCI,FCDRF,BRMP,LMI,FREDERICK,MD. AFRRI,DEPT EXPTL HEMATOL,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1993 VL 21 IS 8 BP 1152 EP 1152 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA MW613 UT WOS:A1993MW61300524 ER PT J AU COOPER, RJ GORDON, MS WEBER, J HOFFMAN, R AF COOPER, RJ GORDON, MS WEBER, J HOFFMAN, R TI THE IN-VIVO ADMINISTRATION OF RECOMBINANT HUMAN INTERLEUKIN-6 (IL-6) TO PATIENTS WITH ADVANCED MALIGNANCIES HAS A PROFOUND EFFECT ON THROMBOPOIESIS SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 INDIANA UNIV,INDIANAPOLIS,IN. NCI,BETHESDA,MD. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1993 VL 21 IS 8 BP 1173 EP 1173 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA MW613 UT WOS:A1993MW61300602 ER PT J AU ORCHARD, PJ DETRICK, RA GORDEN, K DUNBAR, CE VALLERA, DA TAYLOR, P MCIVOR, RS BLAZAR, BR AF ORCHARD, PJ DETRICK, RA GORDEN, K DUNBAR, CE VALLERA, DA TAYLOR, P MCIVOR, RS BLAZAR, BR TI RETROVIRAL-MEDIATED TRANSFER OF THE MURINE INTERLEUKIN-3 GENE ENGINEERED FOR INTRACELLULAR RETENTION RESULTS IN A MYELOPROLIFERATIVE SYNDROME BUT IS ASSOCIATED WITH CIRCULATING INTERLEUKIN-3 LEVELS SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE IL3; RETROVIRUS; AUTOCRINE; MARROW TRANSPLANT ID ACUTE MYELOBLASTIC-LEUKEMIA; COLONY-STIMULATING FACTOR; LUMINAL ER PROTEINS; GM-CSF; HEMATOPOIETIC-CELLS; BLAST CELLS; AUTOCRINE STIMULATION; AUTONOMOUS GROWTH; MYELOID-LEUKEMIA; EXPRESSION AB Myeloid leukemias have been shown to secrete as well as respond to cytokines such as interleukin-3 (IL-3) with an increased growth rate and may therefore become self-stimulatory through an external autocrine mechanism. In vitro evidence that IL-3 is functional within the intracellular compartment has been obtained through modification of the murine IL-3 gene to encode for the amino acids SEKDEL on the carboxyl terminus of the protein, resulting in preferential intracellular retention. The ability of bone marrow-derived hematopoietic progenitor cells to increase their proliferative capacity through intracellular mechanisms was investigated in vivo using retroviruses containing the wild-type or SEKDEL-modified IL-3 gene, transcriptionally regulated by the retroviral long terminal repeat (LTR) or by the SV40 early promoter, in lethally irradiated, bone marrow-reconstituted mice. Bone marrow cells exposed to the N2KDEL virus containing the SEKDEL-modified IL-3 gene were shown by bioassay to retain large amounts of IL-3 intracellularly, and the presence of an integrated provirus containing the SEKDEL sequences was demonstrated by polymerase chain reaction (PCR) in the spleen and bone marrow of these animals. Transduction with all four types of IL-3 viruses resulted in dramatic increases in the circulating white blood cell (WBC) count; this myeloproliferative state occurred within several weeks following bone marrow transplantation (BMT), when viruses expressing the IL-3 or modified gene were under transcriptional regulation of the viral LTR, and approximately 2 months post-BMT, when they were under control of the SV40 internal promoter. Serum levels of IL-3 were measured in transplanted animals and found to be markedly increased in each case in which WBC elevation was observed, including mice receiving marrow transduced with constructs containing the IL-3 gene modified for intracellular retention. No animals were observed in which myeloproliferation occurred without secretion. From these experiments, it seems unlikely that exclusively intracellular mechanisms are a major contributor to the development of the myeloproliferative syndrome observed in these animals. C1 UNIV MINNESOTA HOSP & CLIN,DEPT PEDIAT,DIV BONE MARROW TRANSPLANTAT,MINNEAPOLIS,MN 55455. UNIV MINNESOTA HOSP & CLIN,INST HUMAN GENET,MINNEAPOLIS,MN. UNIV MINNESOTA HOSP & CLIN,DEPT LAB MED & PATHOL,MINNEAPOLIS,MN 55455. UNIV MINNESOTA HOSP & CLIN,DEPT THERAPEUT RADIOL,MINNEAPOLIS,MN 55455. NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [P01-CA21737]; NIAID NIH HHS [N01-AI-85002] NR 43 TC 11 Z9 11 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 1993 VL 21 IS 9 BP 1245 EP 1254 PG 10 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA MW614 UT WOS:A1993MW61400008 PM 8330649 ER PT J AU CHHABRA, RS BUCHER, JR HASEMAN, JK ELWELL, MR KURTZ, PJ CARLTON, BD AF CHHABRA, RS BUCHER, JR HASEMAN, JK ELWELL, MR KURTZ, PJ CARLTON, BD TI COMPARATIVE CARCINOGENICITY OF 5,5-DIPHENYLHYDANTOIN WITH OR WITHOUT PERINATAL EXPOSURE IN RATS AND MICE SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID MALIGNANT LYMPHOMA; EPILEPTIC PATIENTS; CHILDHOOD-CANCER; LONG-TERM; PHENYTOIN; PARENTS; TUMORS; DIPHENYLHYDANTOIN; TOXICOLOGY; DILANTIN C1 BATTELLE MEM INST,COLUMBUS,OH 43201. RP CHHABRA, RS (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 53 TC 12 Z9 12 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 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD AUG PY 1993 VL 21 IS 2 BP 174 EP 186 DI 10.1006/faat.1993.1087 PG 13 WC Toxicology SC Toxicology GA LT275 UT WOS:A1993LT27500006 PM 8405780 ER PT J AU FIJALKOWSKA, IJ DUNN, RL SCHAAPER, RM AF FIJALKOWSKA, IJ DUNN, RL SCHAAPER, RM TI MUTANTS OF ESCHERICHIA-COLI WITH INCREASED FIDELITY OF DNA-REPLICATION SO GENETICS LA English DT Article ID POLYMERASE-III HOLOENZYME; SPONTANEOUS MUTATION; MISMATCH REPAIR; CB120 ANTIMUTATOR; MUTT PROTEIN; MUTAGENESIS; GENE; STRAINS; MECHANISMS; FREQUENCY AB To improve our understanding of the role of DNA replication fidelity in mutagenesis, we undertook a search for Escherichia coli antimutator strains with increased fidelity of DNA replication. The region between 4 and 5 min of the E. coli chromosome was mutagenized using localized mutagenesis mediated by bacteriophage P1. This region contains the dnaE and dnaQ genes, which encode, respectively, the DNA polymerase (alpha subunit) and 3' exonucleolytic proofreading activity (epsilon subunit) of DNA polymerase III holoenzyme, the enzyme primarily responsible for replicating the bacterial chromosome. The mutated bacteria were screened for antimutator phenotype in a strain defective in DNA mismatch repair (mutL), using a papillation assay based on the reversion of the galK2 mutation. In a mutL strain, mutations result primarily from DNA replication errors. Among 10,000 colonies, seven mutants were obtained whose level of papillation was reduced 5-30-fold. These mutants also displayed decreased mutation frequencies for rifampicin or nalidixic acid resistance as well as for other markers. Mapping by PI transduction and complementation showed each to reside in dnaE. These observations support the idea that the mutants represent antimutators which replicate their DNA with increased fidelity. Mutation rates were reduced in both mutL and mutT backgrounds, but mutagenesis by ultraviolet light was not significantly affected, suggesting that the antimutator effect may be largely restricted to normal DNA replication. RP FIJALKOWSKA, IJ (reprint author), NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709, USA. RI Fijalkowska, Iwona/I-7796-2016 NR 48 TC 71 Z9 71 U1 0 U2 2 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD AUG PY 1993 VL 134 IS 4 BP 1023 EP 1030 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA LP873 UT WOS:A1993LP87300004 PM 8375645 ER PT J AU SCHAAPER, RM AF SCHAAPER, RM TI THE MUTATIONAL SPECIFICITY OF 2 ESCHERICHIA-COLI DNAE-ANTIMUTATOR ALLELES AS DETERMINED FROM LACI MUTATION SPECTRA SO GENETICS LA English DT Article ID POLYMERASE-III HOLOENZYME; I KLENOW FRAGMENT; SPONTANEOUS MUTAGENESIS; NUCLEOTIDE SELECTION; CB120 ANTIMUTATOR; BASE-SUBSTITUTION; MISMATCH REPAIR; MUTT PROTEIN; MUTANT; BACTERIOPHAGE-T4 AB In a companion study we have described the isolation of a series of mutants of Escherichia coli that replicate their DNA with increased fidelity. These mutants carry a mutation in the dnaE gene, encoding the alpha (polymerase) subunit of DNA polymerase III holoenzyme, which is responsible for the faithful replication of the bacterial chromosome. The mutants were detected as suppressors of the high mutability of a mutL strain (defective in postreplicative mismatch correction), in which mutations may be considered to arise predominantly from errors of DNA replication. To investigate the specificity of these antimutator effects, we have analyzed spectra of forward mutations in the N-terminal part of the lacI gene (i(-d) mutations) for two of the mutL dnaE derivatives (dnaE911 and dnaE915), as well as the control mutL strain. DNA sequencing of over 600 mutants revealed that in the mutL background both antimutator alleles reduce specifically transition mutations (A.T --> G.C and G.C --> A.T). However, the two alleles behave differently in this respect. dnaE911 reduces A.T --> G.C more strongly than it does G.C --> A.T, whereas the reverse is true for dnaE915. Second, dnaE911 does not appear to affect either transversion or frameshift mutations, whereas dnaE915 displays a distinct mutator effect for both. This mutator effect of dnaE915 for frameshift mutations was confirmed by the frequency of reversion of the trpE9777 frameshift mutation. The discovery that dnaE antimutator alleles possess distinct specificities supports the notion that DNA polymerases discriminate against errors along multiple pathways and that these pathways can be influenced independently. RP SCHAAPER, RM (reprint author), NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709, USA. NR 47 TC 38 Z9 38 U1 2 U2 2 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD AUG PY 1993 VL 134 IS 4 BP 1031 EP 1038 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA LP873 UT WOS:A1993LP87300005 PM 8375646 ER PT J AU FIJALKOWSKA, IJ SCHAAPER, RM AF FIJALKOWSKA, IJ SCHAAPER, RM TI ANTIMUTATOR MUTATIONS IN THE ALPHA-SUBUNIT OF ESCHERICHIA-COLI DNA-POLYMERASE .3. IDENTIFICATION OF THE RESPONSIBLE MUTATIONS AND ALIGNMENT WITH OTHER DNA-POLYMERASES SO GENETICS LA English DT Article ID I KLENOW FRAGMENT; III HOLOENZYME; REPLICATION FIDELITY; EDITING EXONUCLEASE; CB120 ANTIMUTATOR; CRYSTAL-STRUCTURE; EPSILON-SUBUNIT; MECHANISM; GENE; FREQUENCY AB The dnaE gene of Escherichia coli encodes the DNA polymerase (alpha subunit) of the main replicative enzyme, DNA polymerase III holoenzyme. We have previously identified this gene as the site of a series of seven antimutator mutations that specifically decrease the level of DNA replication errors. Here we report the nucleotide sequence changes in each of the different antimutator dnaE alleles. For each a single, but different, amino acid substitution was found among the 1,160 amino acids of the protein. The observed substitutions are generally nonconservative. All affected residues are located in the central one-third of the protein. Some insight into the function of the regions of polymerase III containing the affected residues was obtained by amino acid alignment with other DNA polymerases. We followed the principles developed in 1990 by M. Delarue et al. who have identified in DNA polymerases from a large number of prokaryotic and eukaryotic sources three highly conserved sequence motifs, which are suggested to contain components of the polymerase active site. We succeeded in finding these three conserved motifs in polymerase III as well. However, none of the amino acid substitutions responsible for the antimutator phenotype occurred at these sites. This and other observations suggest that the effect of these mutations may be exerted indirectly through effects on polymerase conformation and/or DNA/polymerase interactions. RP FIJALKOWSKA, IJ (reprint author), NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709, USA. RI Fijalkowska, Iwona/I-7796-2016 NR 41 TC 39 Z9 40 U1 0 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD AUG PY 1993 VL 134 IS 4 BP 1039 EP 1044 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA LP873 UT WOS:A1993LP87300006 PM 8375647 ER PT J AU THON, G KLAR, AJS AF THON, G KLAR, AJS TI DIRECTIONALITY OF FISSION YEAST MATING-TYPE INTERCONVERSION IS CONTROLLED BY THE LOCATION OF THE DONOR LOCI SO GENETICS LA English DT Article ID SCHIZOSACCHAROMYCES-POMBE; MEIOTIC RECOMBINATION; EXPRESSION; CASSETTES; GENES; CELLS; TRANSPOSITION; INITIATION; REGION; BREAKS AB Cells of homothallic strains of Schizosaccharomyces pombe efficiently switch between two mating types called P and M. The phenotypic switches are due to conversion of the expressed mating-type locus (mat1) by two closely linked silent loci, mat2-P and mat3-M, that contain unexpressed information for the P and M mating types, respectively. In this process, switching-competent cells switch to the opposite mating type in 72-90% of the cell divisions. Hence, mat2-P is a preferred donor of information to mat1 in M cells, whereas mat3-M is a preferred donor in P cells. We investigated the reason for the donor preference by constructing a strain in which the genetic contents of the donor loci were swapped. We found that switching to the opposite mating type was very inefficient in that strain. This shows that the location of the silent cassettes in the chromosome, rather than their content, is the deciding factor for recognition of the donor for each cell type. We propose a model in which switching is achieved by regulating accessibility of the donor loci, perhaps by changing the chromatin structure in the mating-type region, thus promoting an intrachromosomal folding of mat2 or mat3 onto mat1 in a cell type-specific fashion. We also present evidence for the involvement of the Swi6 and Swi6-mod trans-acting factors in the donor-choice mechanism. We suggest that these factors participate in forming the proposed folded structure. RP NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, EUKARYOT GENE EXPRESS LAB, FREDERICK, MD 21702 USA. RI Thon, Genevieve/L-9497-2014 OI Thon, Genevieve/0000-0001-8550-5945 FU NCI NIH HHS [N01-CO-74101] NR 34 TC 59 Z9 59 U1 0 U2 2 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD AUG PY 1993 VL 134 IS 4 BP 1045 EP 1054 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA LP873 UT WOS:A1993LP87300007 PM 8375648 ER PT J AU GOULDING, M STERRER, S FLEMING, J BALLING, R NADEAU, J MOORE, KJ BROWN, SDM STEEL, KP GRUSS, P AF GOULDING, M STERRER, S FLEMING, J BALLING, R NADEAU, J MOORE, KJ BROWN, SDM STEEL, KP GRUSS, P TI ANALYSIS OF THE PAX-3 GENE IN THE MOUSE MUTANT SPLOTCH SO GENOMICS LA English DT Article ID WAARDENBURG SYNDROME TYPE-1; NEURAL-TUBE DEFECTS; HUP2 PAIRED DOMAIN; HUMAN HOMOLOG; MUTATION; BOX; CHROMOSOME-1; DELETION; PROTEIN; LINKAGE C1 SALK INST BIOL STUDIES,MOLEC NEUROBIOL LAB,LA JOLLA,CA 92037. MRC,INST HEARING RES,NOTTINGHAM NG7 2RD,ENGLAND. JACKSON LAB,BAR HARBOR,ME 04609. FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. ST MARYS HOSP,SCH MED,DEPT BIOCHEM & MOLEC GENET,LONDON W2 1PG,ENGLAND. RP GOULDING, M (reprint author), MAX PLANCK INST BIOPHYS CHEM,DEPT MOLEC CELL BIOL,AM FASSBERG,W-3400 GOTTINGEN,GERMANY. FU NCI NIH HHS [N01-CO-74101]; NICHD NIH HHS [HD25389] NR 38 TC 107 Z9 108 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 AUG PY 1993 VL 17 IS 2 BP 355 EP 363 DI 10.1006/geno.1993.1332 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA LP815 UT WOS:A1993LP81500012 PM 8406486 ER PT J AU KERR, JM FISHER, LW TERMINE, JD WANG, MG MCBRIDE, OW YOUNG, MF AF KERR, JM FISHER, LW TERMINE, JD WANG, MG MCBRIDE, OW YOUNG, MF TI THE HUMAN BONE SIALOPROTEIN GENE (IBSP) - GENOMIC LOCALIZATION AND CHARACTERIZATION SO GENOMICS LA English DT Article ID MINERALIZED-TISSUE FORMATION; COMPLETE NUCLEOTIDE-SEQUENCE; SECRETED PHOSPHOPROTEIN-1; MESSENGER-RNA; Z-DNA; SULFATE PROTEOGLYCAN; CELLS-INVITRO; LONG ARM; EXPRESSION; OSTEOPONTIN C1 NCI,BETHESDA,MD 20892. RP KERR, JM (reprint author), NIDR,BONE RES BRANCH,BLDG 30,RM 106,BETHESDA,MD 20892, USA. NR 42 TC 56 Z9 57 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 AUG PY 1993 VL 17 IS 2 BP 408 EP 415 DI 10.1006/geno.1993.1340 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA LP815 UT WOS:A1993LP81500020 PM 8406493 ER PT J AU SCHERER, SS KAMHOLZ, J JAKOWLEW, SB AF SCHERER, SS KAMHOLZ, J JAKOWLEW, SB TI AXONS MODULATE THE EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETAS IN SCHWANN-CELLS SO GLIA LA English DT Article DE WALLERIAN DEGENERATION; PERIPHERAL NERVE; AXONAL REGENERATION ID RAT SCIATIC-NERVE; WALLERIAN DEGENERATION; TGF-BETA; PERIPHERAL MYELIN; GENE-EXPRESSION; SENSORY NEURONS; RNA EXPRESSION; MOUSE EMBRYO; FACTOR-BETA-1; PROTEIN AB We have investigated the expression of transforming growth factor (TGF)-beta1, -beta2, and -beta3 in developing, degenerating, and regenerating rat peripheral nerve by immunohistochemistry and Northern blot analysis. In normal adult sciatic nerve, TGF-beta1,-beta2, and -beta3 are detected in the cytoplasm of Schwann cells, and the levels of TGF-beta1 and -beta3 mRNAs are constant during post-natal development. When sciatic nerves are transected to cause axonal degeneration and prevent axonal regeneration, the level of TGF-beta1 mRNA in the distal nerve-stump increases markedly and remains elevated, whereas the level of TGF-beta3 mRNA falls modestly and remains depressed. When sciatic nerves are crushed to cause axonal degeneration and allow axonal regeneration, the level of TGF-beta1 mRNA initially increases as axons degenerate, and then falls as axons regenerate. TGF-beta2 mRNA was not detected in developing or lesioned sciatic nerves at any time. Cultured Schwann cells have high levels of TGF-beta1 mRNA, the amount of which is reduced by forskolin, which mimicks the effect of axonal contact. These data demonstrate that Schwann cells express TGF-beta1, -beta2, and -beta3, and that TGF-beta1 and -beta3 mRNA predominate over TGF-beta2 mRNA in peripheral nerve. Axonal contact and forskolin decrease the expression of TGF-beta1 in Schwann cells. (C) 1993 Wiley-Liss, Inc. C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. RP SCHERER, SS (reprint author), HOSP UNIV PENN,DEPT NEUROL,3400 SPRUCE ST,PHILADELPHIA,PA 19104, USA. NR 90 TC 91 Z9 92 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 0894-1491 J9 GLIA JI Glia PD AUG PY 1993 VL 8 IS 4 BP 265 EP 276 DI 10.1002/glia.440080407 PG 12 WC Neurosciences SC Neurosciences & Neurology GA LP872 UT WOS:A1993LP87200006 PM 8406683 ER PT J AU DUFFIN, KL LANGE, GW WELPLY, JK FLORMAN, R OBRIEN, PJ DELL, A REASON, AJ MORRIS, HR FLIESLER, SJ AF DUFFIN, KL LANGE, GW WELPLY, JK FLORMAN, R OBRIEN, PJ DELL, A REASON, AJ MORRIS, HR FLIESLER, SJ TI IDENTIFICATION AND OLIGOSACCHARIDE STRUCTURE-ANALYSIS OF RHODOPSIN GLYCOFORMS CONTAINING GALACTOSE AND SIALIC-ACID SO GLYCOBIOLOGY LA English DT Article DE GLYCOFORM; OLIGOSACCHARIDE STRUCTURE; RHODOPSIN ID OUTER SEGMENT MEMBRANES; N-LINKED OLIGOSACCHARIDES; LECTIN BINDING-SITES; PHOTORECEPTOR CELLS; ULTRASTRUCTURAL-LOCALIZATION; RETINAL PHOTORECEPTORS; PIGMENT-EPITHELIUM; MASS-SPECTROMETRY; BOVINE RHODOPSIN; RECEPTORS AB The N-linked oligosaccharides of frog (Rana pipiens) rhodopsin were analysed by sequential exoglycosidase digestion and gel filtration chromatography, following reductive tritiation. In addition, selected tryptic glycopeptides obtained from frog retinal rod outer segment membranes were examined by electrospray mass spectrometry (ES-MS), fast atom bombardment mass spectrometry (FAB-MS), amino acid sequence and composition analysis, and carbohydrate composition analysis. The amino acid sequence data demonstrated that the glycopeptides were derived from rhodopsin and confirmed the presence of two N-glycosylation sites, at residues Asn2 and Asn15. The predominant glycan (approximately 60% of total) had the structure GlcNAcbeta1-2Manalpha1-3(Manalpha1-6) Manbeta1-4GlcNAcbeta1-4GlcNAc-(Asn), with the remaining structures containing 1-3 additional hexose residues, as reported previously for bovine rhodopsin. Unlike bovine rhodopsin, however, a sizable fraction of the total glycans of frog rhodopsin also contained sialic acid (NeuAc), with the sialylated oligosaccharides being present exclusively at the Asn2 site. FAB-MS analysis of oligosaccharides released from the Asn2 site gave, among other signals, an abundant quasimolecular ion corresponding to a glycan of composition NeuAc1Hex6HexNAc3 (where Hex is hexose and HexNAc is N-acetylhexosamine), consistent with a hybrid structure. The potential biological implications of these results are discussed in the context of rod outer segment membrane renewal. C1 EYE INST,1755 S GRAND BLVD,ST LOUIS,MO 63104. MONSANTO CO,RES,ST LOUIS,MO 63198. NIH,BETHESDA,MD 20892. UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,DEPT BIOCHEM,LONDON SW7 2AZ,ENGLAND. ST LOUIS UNIV,SCH MED,EA DOISY DEPT BIOCHEM & MOLEC BIOL,ST LOUIS,MO 63104. FU NEI NIH HHS [NEI#EY06045] NR 60 TC 25 Z9 26 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD AUG PY 1993 VL 3 IS 4 BP 365 EP 380 DI 10.1093/glycob/3.4.365 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LU477 UT WOS:A1993LU47700012 PM 8400551 ER PT J AU CALABRO, A HASCALL, VC AF CALABRO, A HASCALL, VC TI THE EFFECTS OF BREFELDIN-A ON THE BIOSYNTHESIS OF AGGRECAN AND HYALURONIC-ACID IN RAT CHONDROSARCOMA CELLS SO GLYCOCONJUGATE JOURNAL LA English DT Meeting Abstract C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0282-0080 J9 GLYCOCONJUGATE J JI Glycoconjugate J. PD AUG PY 1993 VL 10 IS 4 BP 250 EP 251 DI 10.1007/BF01209899 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LY104 UT WOS:A1993LY10400098 ER PT J AU BYSTRICKY, S SZU, SC AF BYSTRICKY, S SZU, SC TI STRUCTURAL-ANALYSIS OF THE VI POLYSACCHARIDE AT VARIOUS DEGREES OF O-ACETYLATION SO GLYCOCONJUGATE JOURNAL LA English DT Meeting Abstract C1 NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0282-0080 J9 GLYCOCONJUGATE J JI Glycoconjugate J. PD AUG PY 1993 VL 10 IS 4 BP 301 EP 302 DI 10.1007/BF01210056 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LY104 UT WOS:A1993LY10400255 ER PT J AU CORNELISON, TL REED, E AF CORNELISON, TL REED, E TI NEPHROTOXICITY AND HYDRATION MANAGEMENT FOR CISPLATIN, CARBOPLATIN, AND ORMAPLATIN SO GYNECOLOGIC ONCOLOGY LA English DT Review ID ACUTE-RENAL-FAILURE; HIGH-DOSE CISPLATIN; CIS-DIAMMINEDICHLOROPLATINUM NSC-119875; FISCHER 344 RAT; MALE F344 RATS; PHASE-I; MANNITOL DIURESIS; THERAPEUTIC INDEX; HYPERTONIC SALINE; COMBINATION CHEMOTHERAPY C1 NCI,MED BRANCH,BETHESDA,MD 20892. NR 142 TC 94 Z9 96 U1 4 U2 9 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 AUG PY 1993 VL 50 IS 2 BP 147 EP 158 DI 10.1006/gyno.1993.1184 PG 12 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA LY188 UT WOS:A1993LY18800003 PM 8375728 ER PT J AU CHANOCK, S AF CHANOCK, S TI EVOLVING RISK-FACTORS FOR INFECTIOUS COMPLICATIONS OF CANCER-THERAPY SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID COLONY-STIMULATING FACTOR; HUMAN-IMMUNODEFICIENCY-VIRUS; BONE-MARROW TRANSPLANTATION; SEVERELY IMMUNOCOMPROMISED PATIENTS; HERPES-SIMPLEX VIRUS; PNEUMOCYSTIS-CARINII; COMBINATION CHEMOTHERAPY; FUNGAL-INFECTIONS; HEPATIC CANDIDIASIS; ACYCLOVIR THERAPY RP CHANOCK, S (reprint author), NCI,PEDIAT BRANCH,BETHESDA,MD 20892, USA. NR 83 TC 55 Z9 55 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD AUG PY 1993 VL 7 IS 4 BP 771 EP 793 PG 23 WC Oncology; Hematology SC Oncology; Hematology GA LN536 UT WOS:A1993LN53600003 PM 8354656 ER PT J AU FREIFELD, AG AF FREIFELD, AG TI THE ANTIMICROBIAL ARMAMENTARIUM SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; PNEUMOCYSTIS-CARINII PNEUMONIA; HERPES-SIMPLEX VIRUS; BONE-MARROW TRANSPLANTATION; PLACEBO-CONTROLLED TRIAL; PROPHYLACTIC TRIMETHOPRIM-SULFAMETHOXAZOLE; GANCICLOVIR-RESISTANT CYTOMEGALOVIRUS; GRANULOCYTOPENIC CANCER-PATIENTS; ACUTE NONLYMPHOCYTIC LEUKEMIA; PIPERACILLIN PLUS AMIKACIN RP FREIFELD, AG (reprint author), NCI,DIV INFECT DIS,PEDIAT BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 138 TC 12 Z9 13 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD AUG PY 1993 VL 7 IS 4 BP 813 EP 839 PG 27 WC Oncology; Hematology SC Oncology; Hematology GA LN536 UT WOS:A1993LN53600005 PM 8354658 ER PT J AU ROILIDES, E PIZZO, PA AF ROILIDES, E PIZZO, PA TI BIOLOGICALS AND HEMATOPOIETIC CYTOKINES IN PREVENTION OR TREATMENT OF INFECTIONS IN IMMUNOCOMPROMISED HOSTS SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID COLONY-STIMULATING FACTOR; TUMOR-NECROSIS-FACTOR; BONE-MARROW TRANSPLANTATION; HUMAN-IMMUNODEFICIENCY-VIRUS; CHRONIC GRANULOMATOUS-DISEASE; INTRAVENOUS IMMUNE GLOBULIN; HUMAN INTERFERON-GAMMA; BLOOD POLYMORPHONUCLEAR NEUTROPHILS; RECOMBINANT HUMAN INTERLEUKIN-3; ATTENUATED VARICELLA VACCINE C1 NCI,PEDIAT BRANCH,BLDG 10,ROOM 13N240,BETHESDA,MD 20892. NR 166 TC 19 Z9 19 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD AUG PY 1993 VL 7 IS 4 BP 841 EP 864 PG 24 WC Oncology; Hematology SC Oncology; Hematology GA LN536 UT WOS:A1993LN53600006 PM 7689074 ER PT J AU DICHTER, JR LEVINE, SJ SHELHAMER, JH AF DICHTER, JR LEVINE, SJ SHELHAMER, JH TI APPROACH TO THE IMMUNOCOMPROMISED HOST WITH PULMONARY SYMPTOMS SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID OPEN-LUNG-BIOPSY; PNEUMOCYSTIS-CARINII PNEUMONIA; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; BONE-MARROW TRANSPLANTATION; COLONY-STIMULATING FACTOR; TRANS-BRONCHIAL BIOPSY; CYTOMEGALO-VIRUS IMMUNOGLOBULIN; BRONCHOALVEOLAR LAVAGE; ACUTE-LEUKEMIA; AEROSOLIZED PENTAMIDINE RP DICHTER, JR (reprint author), NIH,CTR CLIN,DEPT CRIT CARE MED,BLDG 10,ROOM 7D43,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 107 TC 23 Z9 25 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD AUG PY 1993 VL 7 IS 4 BP 887 EP 912 PG 26 WC Oncology; Hematology SC Oncology; Hematology GA LN536 UT WOS:A1993LN53600008 PM 8354660 ER PT J AU PIZZO, PA AF PIZZO, PA TI INFECTIOUS COMPLICATIONS IN THE IMMUNOCOMPROMISED HOST .1. PREFACE SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Editorial Material RP PIZZO, PA (reprint author), NCI,PEDIAT BRANCH,BLDG 10,ROOM 13N240,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 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD AUG PY 1993 VL 7 IS 4 BP R11 EP R12 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA LN536 UT WOS:A1993LN53600001 ER PT J AU YU, QS LI, YQ LUO, WM BROSSI, A AF YU, QS LI, YQ LUO, WM BROSSI, A TI (S)-1,3-DIMETHYL-3-HYDROXY-5-METHOXYOXINDOLE - BY-PRODUCT IN THE SYNTHESIS OF PHYSOSTIGMINE SO HETEROCYCLES LA English DT Article AB (S)-1,3-Dimethyl-3-hydroxy-5-methoxyoxindole (4) was obtained as a by-product in the asymmetric alkylation of oxindole (1) with methyl chloroacetate in the presence of N-[(4-trifluoromethyl)benzyl]cinchonium bromide. Its structure was established by spectral data. Optically active (4) of (S)-configuration was obtained from oxindole (1) on air oxidation in the presence of the chiral catalyst N-[(4-trifluoromethyl)benzyl]cinchonium bromide. C1 GEORGETOWN UNIV,DEPT CHEM,WASHINGTON,DC 20057. NATL INST DIABET & DIGEST & KIDNEY DIS,BETHESDA,MD 20892. RP YU, QS (reprint author), ACAD SINICA,SHANGHAI INST ORGAN CHEM,SHANGHAI 200032,PEOPLES R CHINA. NR 3 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0385-5414 J9 HETEROCYCLES JI Heterocycles PD AUG 1 PY 1993 VL 36 IS 8 BP 1791 EP 1794 PG 4 WC Chemistry, Organic SC Chemistry GA LL770 UT WOS:A1993LL77000013 ER PT J AU SCHREIBER, JL BREIER, A PICKAR, D AF SCHREIBER, JL BREIER, A PICKAR, D TI HOSPITAL VS COMMUNITY SO HOSPITAL AND COMMUNITY PSYCHIATRY LA English DT Letter RP SCHREIBER, JL (reprint author), NIMH,EXPTL THERAPEUT BRANCH,CLIN STUDIES SECT,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0022-1597 J9 HOSP COMMUNITY PSYCH PD AUG PY 1993 VL 44 IS 8 BP 795 EP 795 PG 1 WC Public, Environmental & Occupational Health; Psychiatry SC Public, Environmental & Occupational Health; Psychiatry GA LP779 UT WOS:A1993LP77900023 PM 8375849 ER PT J AU MACKAY, CR AF MACKAY, CR TI DISCUSSION POINTS TO CONSIDER IN RESEARCH RELATED TO THE HUMAN GENOME SO HUMAN GENE THERAPY LA English DT Article ID MYOCARDIAL-INFARCTION; RISK; DISEASE AB The advances in DNA technology and molecular genetics, spurred by the Human Genome Project, have created new challenges for human subjects research and the system of institutional review board (IRB) review. The populations to be studied are vulnerable because of genetic diseases or risk for them; until now, IRB review has concentrated on overt physical and medical hazards. Attention to the interests of individuals and families participating in, or affected by, research on the human genome frames the agenda for IRB deliberations and suggests the information to be conveyed to prospective participants. By a series of questions, this article explores how human genome research involves a distinct paradigm in human subjects research with its own imperatives for researchers and IRBs. RP MACKAY, CR (reprint author), NIH,BLDG 31,ROOM SB33,BETHESDA,MD 20892, USA. NR 88 TC 6 Z9 6 U1 1 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD AUG PY 1993 VL 4 IS 4 BP 477 EP 495 PG 19 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA LU387 UT WOS:A1993LU38700009 PM 8399493 ER PT J AU PHIPPS, ME MAHER, ER AFFARA, NA LATIF, F LEVERSHA, MA FERGUSONSMITH, ME NAKAMURA, Y LERMAN, M ZBAR, B FERGUSONSMITH, MA AF PHIPPS, ME MAHER, ER AFFARA, NA LATIF, F LEVERSHA, MA FERGUSONSMITH, ME NAKAMURA, Y LERMAN, M ZBAR, B FERGUSONSMITH, MA TI PHYSICAL MAPPING OF CHROMOSOME 3P25-P26 BY FLUORESCENCE IN-SITU HYBRIDIZATION (FISH) SO HUMAN GENETICS LA English DT Article ID VONHIPPEL-LINDAU DISEASE; SMALL REGION; SHORT ARM; HYBRIDIZATION; DELETION; GENETICS; MARKERS AB As part of our effort to isolate and characterise the von Hippel-Lindau (VHL) disease gene, we constructed a physical map of chromosome 3p25-26 by fluorescence in situ hybridisation (FISH) studies on a panel of cytogenetic rearrangements involving this region. Biotinylated cosmid and lambda probes were hybridised to metaphase chromosome spreads and positioned with respect to each cytogenetic breakpoint. These studies unequivocally established the order of five loci linked to the VHL disease gene: cen-(RAF1,312)-D3S732-D3S1250-D3S601-D3S18-pter and determined the position of three other probes within this map. These results ordered RAF1 and D3S732 for the first time, confirmed the localisation of D3S1250 between RAF1 and D3S601 and determined the position of D3S651 with respect to other chromosome 3p25-p26 loci. The establishment of an ordered set of cytogenetic aberrations will enable the rapid assignment of polymorphic and nonpolymorphic cloned sequences within the chromosome region 3p25-p26. C1 UNIV CAMBRIDGE,DEPT PATHOL,CAMBRIDGE,ENGLAND. NCI,FREDERICK CANC RES FACIL,IMMUNOBIOL LAB,FREDERICK,MD 21701. JAPANESE FDN CANC RES,INST CANC,TOKYO 170,JAPAN. RI MAHER, EAMONN/A-9507-2008 OI MAHER, EAMONN/0000-0002-6226-6918 NR 21 TC 9 Z9 9 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD AUG PY 1993 VL 92 IS 1 BP 18 EP 22 DI 10.1007/BF00216139 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA LV013 UT WOS:A1993LV01300004 PM 8365722 ER PT J AU LI, H SCHMIDT, L DUH, FMC WEI, MH LATIF, F STACKHOUSE, T LERMAN, MI ZBAR, B TORY, K AF LI, H SCHMIDT, L DUH, FMC WEI, MH LATIF, F STACKHOUSE, T LERMAN, MI ZBAR, B TORY, K TI 3 POLYMORPHIC DINUCLEOTIDE REPEATS NEAR THE VONHIPPEL-LINDAU (VHL) DISEASE GENE ON HUMAN CHROMOSOME-3 - D3S587, D3S1317, D3S1435 SO HUMAN MOLECULAR GENETICS LA English DT Note C1 NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS & DEV,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 21702. NR 2 TC 18 Z9 18 U1 0 U2 4 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD AUG PY 1993 VL 2 IS 8 BP 1326 EP 1326 DI 10.1093/hmg/2.8.1326 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA LV836 UT WOS:A1993LV83600043 PM 8401520 ER PT J AU LI, H SCHMIDT, L WEI, MH HUSTAD, T LERMAN, MI ZBAR, B TORY, K AF LI, H SCHMIDT, L WEI, MH HUSTAD, T LERMAN, MI ZBAR, B TORY, K TI 3 TETRANUCLEOTIDE POLYMORPHISMS FOR LOCI - D3S1352, D3S1358, D3S1359 SO HUMAN MOLECULAR GENETICS LA English DT Note C1 NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 21702. NR 3 TC 65 Z9 68 U1 0 U2 5 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD AUG PY 1993 VL 2 IS 8 BP 1327 EP 1327 DI 10.1093/hmg/2.8.1327 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA LV836 UT WOS:A1993LV83600044 PM 8401521 ER PT J AU CORDARO, MA SONIES, BC AF CORDARO, MA SONIES, BC TI AN IMAGE-PROCESSING SCHEME TO QUANTITATIVELY EXTRACT AND VALIDATE HYOID BONE MOTION BASED ON REAL-TIME ULTRASOUND RECORDINGS OF SWALLOWING SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Note AB An image processing technique with associated hardware mas developed to quantitatively extract hyoid bone motion from realtime submandibular ultrasound images recorded during the swallowing act. Videofluorographic imaging, the ''gold standard'' of swallowing studies, was recorded simultaneously and synchronized to the ultrasound. Hyoid position obtained from the ultrasound was validated based on the videofluorography using personal computer-based image processing methods. C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT REHABIL MED,BETHESDA,MD 20892. RP CORDARO, MA (reprint author), ACW RES INC,BROOKLYN,NY 11204, USA. NR 7 TC 5 Z9 6 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD AUG PY 1993 VL 40 IS 8 BP 841 EP 844 DI 10.1109/10.238473 PG 4 WC Engineering, Biomedical SC Engineering GA MD453 UT WOS:A1993MD45300017 PM 8258453 ER PT J AU SUTER, JJ PORET, JC ROSEN, M RIFKIND, JM AF SUTER, JJ PORET, JC ROSEN, M RIFKIND, JM TI IONIZING-RADIATION DETECTOR USING MULTIMODE OPTICAL FIBERS SO IEEE TRANSACTIONS ON NUCLEAR SCIENCE LA English DT Article; Proceedings Paper CT 1992 IEEE NUCLEAR SCIENCE SYMP / MEDICAL IMAGING CONF ( NSS/MIC ) CY OCT 25-31, 1992 CL ORLANDO, FL SP IEEE ID RESONANCE; CENTERS AB An optical ionizing radiation detector, based on the attenuation of 850-mn light in 50/125-mum multimode fibers, is described. The detector is especially well suited for application on spacecraft because of its small design. The detection element consists of a section of coiled fibers that has been designed to strip higher-order optical modes. Cylindrical radiation shields with atomic numbers ranging from Z = 13 (aluminum) to Z = 82 (lead) were placed around the ionizing radiation detector so that the effectiveness of the detector could be measured. By exposing the shields and the detector to 1.25-MeV cobalt 60 radiation, the mass attenuation coefficients of the shields were measured. The detector is based on the phenomenon that radiation creates optical color centers in glass fibers. Electron spin resonance spectroscopy performed on the 50/125-mum fibers showed the presence of germanium oxide and phosphorus-based color centers. The intensity of these centers is directly related to the accumulated gamma radiation. C1 JOHNS HOPKINS UNIV,DEPT MAT SCI & ENGN,BALTIMORE,MD 21218. NIH,CELLULAR & MOLEC BIOL LAB,BALTIMORE,MD 21224. RP SUTER, JJ (reprint author), JOHNS HOPKINS UNIV,APPL PHYS LAB,LAUREL,MD 20723, USA. NR 9 TC 5 Z9 9 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0018-9499 J9 IEEE T NUCL SCI JI IEEE Trans. Nucl. Sci. PD AUG PY 1993 VL 40 IS 4 BP 466 EP 469 DI 10.1109/23.256602 PN 1 PG 4 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA LV991 UT WOS:A1993LV99100032 ER PT J AU FAUNTLEROY, MB ASOFSKY, R BAKER, PJ HRABA, T BROOKS, A STASHAK, P TAYLOR, CE AF FAUNTLEROY, MB ASOFSKY, R BAKER, PJ HRABA, T BROOKS, A STASHAK, P TAYLOR, CE TI EFFECTS OF IL-4 DEPLETION ON THE ANTIBODY-RESPONSE TO PSEUDOMONAS-AERUGINOSA LIPOPOLYSACCHARIDE IN MICE SO IMMUNOBIOLOGY LA English DT Article ID HUMAN B-CELLS; BACTERIAL POLYSACCHARIDE ANTIGENS; III PNEUMOCOCCAL POLYSACCHARIDE; SUPPRESSOR T-CELLS; CYSTIC-FIBROSIS; IGE PRODUCTION; LIPID-A; INTERLEUKIN-4; EXPRESSION; MODULATION AB These studies were done to examine the role of interleukin-4 (IL-4) in the generation of isotype specific antibody responses of mice to Pseudomonas aeruginosa lipopolysaccharide (PALPS) by neutralization of IL-4 in vivo using anti-IL-4 antibody (11B11). We found that the administration of anti-IL-4 antibody (11B11) 24h before immunization with PALPS resulted in a decreased PALPS-specific antibody response for all isotypes examined (IgM, IgG1, IgG2a, IgG2b, IgG3). By contrast, we observed that the non-antigen-specific (polyclonal) IgM response of mice following treatment with 11B11 antibody and PALPS was increased while the polyclonal responses for the other isotypes were unaffected. When mice were given recombinant IL-10 at the time of immunization with PALPS there was a decrease in the PALPS-specific antibody response but an increase in the polyclonal IgM, IgG2a, IgG2b, IgG3 response whereas the polyclonal IgG1 response was decreased by a five-fold margin. The results of these studies suggest that both the antigen-specific and the polyclonal response can be influenced in a different manner by IL-4 or by IL-10. C1 NIAID,IMMUNOGENET LAB,TWINBROOK 2 RES FACIL,12441 PARKLAWN DR,BETHESDA,MD 20892. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. NR 54 TC 3 Z9 3 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 AUG PY 1993 VL 188 IS 4-5 BP 379 EP 391 PG 13 WC Immunology SC Immunology GA LV553 UT WOS:A1993LV55300006 PM 8244445 ER PT J AU TESH, VL BURRIS, JA OWENS, JW GORDON, VM WADOLKOWSKI, EA OBRIEN, AD SAMUEL, JE AF TESH, VL BURRIS, JA OWENS, JW GORDON, VM WADOLKOWSKI, EA OBRIEN, AD SAMUEL, JE TI COMPARISON OF THE RELATIVE TOXICITIES OF SHIGA-LIKE TOXINS TYPE-I AND TYPE-II FOR MICE SO INFECTION AND IMMUNITY LA English DT Article ID ESCHERICHIA-COLI O157-H7; HEMOLYTIC UREMIC SYNDROME; VASCULAR ENDOTHELIAL-CELLS; TRANSFER RNA-BINDING; MONOCLONAL-ANTIBODIES; SHIGELLA TOXIN; NUCLEOTIDE-SEQUENCE; PROTEIN-SYNTHESIS; HYBRID TOXINS; CYTO-TOXIN AB In earlier studies using a streptomycin-treated mouse model of infection caused by enterobemorrhagic Escherichia coli (EHEC), animals fed Shiga-like toxin type II (SLT-II)-producing strains developed acute renal cortical necrosis and died, while mice fed Shiga-like toxin type I (SLT-I)-producing clones did not die (E. A. Wadolkowski, L. M. Sung, J. A. Burris, J. E. Samuel, and A. D. O'Brien, Infect. Immun. 58:3959-3965, 1990). To examine the bases for the differences we noted between the two toxins in the murine infection model, we injected mice with purified toxins and carried out histopathological examinations. Despite the genetic and structural similarities between the two toxins, SLT-II had a 50% lethal dose (LD50) which was approximately 400 times lower than that of SLT-I when injected intravenously or intraperitoneally into mice. Histopathologic examination of toxin-injected mice revealed that detectable damage was limited to renal cortical tubule epithelial cells. Passive administration of anti-SLT-II antibodies protected mice from SLT-II-mediated kidney damage and death. Immunofluorescence staining of normal murine kidney sections incubated with purified SLT-I or SLT-II demonstrated that both toxins bound to cortical tubule and medullary duct epithelial cells. Compared with SLT-I, SLT-II was more heat and pH stable, suggesting that SLT-II is a relatively more stable macromolecule. Although both toxins bound to globotriaosylceramide, SLT-1 bound with a higher affinity in a solid-phase binding assay. Differences in enzymatic activity between the two toxins were not detected. These data suggest that structural/functional differences between the two toxins, possibly involving holotoxin stability and/or receptor affinity, may contribute to the differential LD50s in mice. C1 MICROCARB INC,GAITHERSBURG,MD 20879. NIH,LAB SCI SECT,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT MICROBIOL,BETHESDA,MD 20814. FU NIAID NIH HHS [5T32-AI 07308-02, AI 20148-09] NR 59 TC 255 Z9 262 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1993 VL 61 IS 8 BP 3392 EP 3402 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LP357 UT WOS:A1993LP35700040 PM 8335369 ER PT J AU PETTER, R ROZENBLATT, S SCHECHTMAN, D WELLEMS, TE MIRELMAN, D AF PETTER, R ROZENBLATT, S SCHECHTMAN, D WELLEMS, TE MIRELMAN, D TI ELECTROPHORETIC KARYOTYPE AND CHROMOSOME ASSIGNMENTS FOR A PATHOGENIC AND A NONPATHOGENIC STRAIN OF ENTAMOEBA-HISTOLYTICA SO INFECTION AND IMMUNITY LA English DT Note ID RIBOSOMAL-RNA GENES; PLASMODIUM-FALCIPARUM; MOLECULAR KARYOTYPE; DNA-MOLECULES; AMEBIASIS; CONSTRUCTION; LEISHMANIA; RESOLUTION; SEQUENCES; CDNA AB The electrophoretic karyotypes of a pathogenic and a nonpathogenic strain of Entamoeba histolytica were determined by pulsed-field gel electrophoresis. A number of previously isolated genes were assigned to specific chromosomal bands. Significant differences between the chromosomal patterns of these strains as well as in the assignment of most genes were found. C1 WEIZMANN INST SCI,MACARTHUR CTR MOLEC BIOL PARASIT DIS,IL-76100 REHOVOT,ISRAEL. WEIZMANN INST SCI,DEPT MEMBRANE RES & BIOPHYS,IL-76100 REHOVOT,ISRAEL. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. TEL AVIV UNIV,DEPT MOLEC MICROBIOL & BIOTECHNOL,IL-69978 TEL AVIV,ISRAEL. RI schechtman, deborah/B-7572-2012 NR 38 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1993 VL 61 IS 8 BP 3574 EP 3577 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LP357 UT WOS:A1993LP35700070 PM 8335392 ER PT J AU RUSSO, TA MOFFITT, MC HAMMER, CH FRANK, MM AF RUSSO, TA MOFFITT, MC HAMMER, CH FRANK, MM TI TNPHOA-MEDIATED DISRUPTION OF K54 CAPSULAR POLYSACCHARIDE GENES IN ESCHERICHIA-COLI CONFERS SERUM SENSITIVITY SO INFECTION AND IMMUNITY LA English DT Note ID URINARY-TRACT INFECTION; ALTERNATIVE COMPLEMENT PATHWAY; C3 CONVERTASE; K1 ANTIGEN; O-ANTIGEN; RESISTANCE; STRAINS; LIPOPOLYSACCHARIDE; VIRULENCE; PATHOGENICITY AB To assess whether non-K1, group 2 capsular serotypes are important in conferring serum resistance to extraintestinal isolates of Escherichia coli, a K54 blood isolate (CP9) was evaluated as a model pathogen. Transposon mutagenesis (TnphoA) was used to generate isogenic capsule-negative mutants. CP9 was resistant to the bactericidal effects of serum, growing in 80% serum. In contrast, all of the capsule-negative mutants had an increased sensitivity to 80% normal human serum, undergoing a 2- to 3-log kill over 3 h when starting inocula of 10(4) to 10(7) CFU/ml were used. The killing of the capsule-negative strains was mediated through the alternative complement pathway and not by lysozyme or beta-lysins. The protective effect of the K54 capsule against the bactericidal activity of serum was not through inhibition of the complement cascade, nor did it appear to be through a difference in the binding of C3. C1 DUKE UNIV,MED CTR,DEPT PEDIAT,DURHAM,NC 27710. RP RUSSO, TA (reprint author), NIAID,CLIN INVEST LAB,BACTERIAL PATHOGENESIS UNIT,BETHESDA,MD 20892, USA. NR 42 TC 27 Z9 27 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 1993 VL 61 IS 8 BP 3578 EP 3582 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LP357 UT WOS:A1993LP35700071 PM 8392976 ER PT J AU TAKAHASHI, H NAKAGAWA, Y YOKOMURO, K BERZOFSKY, JA AF TAKAHASHI, H NAKAGAWA, Y YOKOMURO, K BERZOFSKY, JA TI INDUCTION OF CD8+ CYTOTOXIC T-LYMPHOCYTES BY IMMUNIZATION WITH SYNGENEIC IRRADIATED HIV-1 ENVELOPE DERIVED PEPTIDE-PULSED DENDRITIC CELLS SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE CYTOTOXIC T-CELLS; DENDRITIC CELLS; PEPTIDE; VACCINATION ID HUMAN-IMMUNODEFICIENCY-VIRUS; FREE SYNTHETIC PEPTIDE; I MHC MOLECULE; MONOCLONAL-ANTIBODIES; ANTIGEN-PRESENTATION; INFECTION INVITRO; B-CELLS; PROTEIN; INVIVO; DETERMINANT AB Based on the evidence that CD8+ cytotoxic T cells (CTL) precursors do not appear to distinguish between virus-infected cells and viral peptide-pulsed syngeneic cells, we have developed methods for priming class I MHC molecule restricted CD8+ CTL with such peptides without using any adjuvant. We were able to prime in vivo such CTL immunity lasting at least 6 months with a single i.v. injection of syngeneic 2200 - 3300 rad irradiated peptide-pulsed spleen cells, and even more efficiently with a very small number of irradiated class II MHC molecule expressing splenic dendritic cells (DC). No foreign serum source was necessary during the pulsing. Interestingly, we could not generate significant CTL activity with unirradiated or low dose (< 1100 rad) irradiated spleen cells. Because even purified DC required irradiation for optimal activity, because unirradiated B cells did not significantly inhibit the immunization with DC, and because B cell depletion did not substitute for irradiation, we believe that the effect of irradiation is more to determine homing of the cells than to eliminate interference by B cells. Intravenous immunization was much more effective than s.c. or i.p. immunization. CTL generated by this method could kill both peptide-pulsed syngeneic targets and targets endogenously expressing the whole gp160 gene. Moreover, we found that we could prime CD8+ CTL with the minimal 10-residue core peptide (RGPGRAFVTI) for optimal presentation by class I MHC molecules as efficiently as the original p18. These results suggested that DC bearing antigenic peptide may prime antigen-specific CD8+ CTL in vivo. These results offer useful information for development of synthetic peptide vaccines and immunotherapy. C1 NCI,MOLEC IMMUNOGENET & VACCINE RES SECT,BETHESDA,MD 20892. RP TAKAHASHI, H (reprint author), NIPPON MED COLL,DEPT MICROBIOL & IMMUNOL,1-1-5 SENDAGI,BUNKYO KU,TOKYO 113,JAPAN. NR 40 TC 129 Z9 132 U1 1 U2 2 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 AUG PY 1993 VL 5 IS 8 BP 849 EP 857 DI 10.1093/intimm/5.8.849 PG 9 WC Immunology SC Immunology GA LR659 UT WOS:A1993LR65900006 PM 8398980 ER PT J AU LYNCH, F SHEVACH, EM AF LYNCH, F SHEVACH, EM TI GAMMA-DELTA T-CELLS PROMOTE CD4 AND CD8 EXPRESSION BY SCID THYMOCYTES SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE DENDRITIC EPIDERMAL T-CELLS; SCID MICE; THYMUS; T-CELL DEVELOPMENT ID MONOCLONAL-ANTIBODY; ANTIGEN RECEPTORS; LYMPHOCYTES; MICE; ACTIVATION; GENERATION; ONTOGENY; TCR AB Molecular studies of the gammadelta TCR, which is expressed by a minor subpopulation of T lymphocytes in all vertebrate species, have defined a subset which expresses a receptor with extreme junctional diversity and a second subset, most commonly found in epithelia, which expresses a receptor of very limited diversity. In the developing murine thymus, gammadelta T cells appear in an ordered sequence of specific V rearrangements, V(gamma)3V(delta)1 on day 14, V(gamma)2V(delta)1 on day 17, and subsequently V(gamma)4V(delta)5, V(delta)6, or V(delta)7. We demonstrate that the transfer of expanded populations of gammadelta cells from newborn thymus and cell lines expressing the invariant V(gamma)3V(delta)1 receptor into SCID mice, which lack T and B cells, results in the appearance of CD3-CD4+CD8+ thymocytes. Thus, one role of the early appearing V(gamma)3V(delta)1 T cells in thymic development in vivo is to promote CD4 and CDS surface expression on precursor cells. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. NR 26 TC 33 Z9 33 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 AUG PY 1993 VL 5 IS 8 BP 991 EP 995 DI 10.1093/intimm/5.8.991 PG 5 WC Immunology SC Immunology GA LR659 UT WOS:A1993LR65900021 PM 8398991 ER PT J AU CLEMENS, J SACK, D RAO, M CHAKRABORTY, J KAY, B AHMED, F KHAN, MR VANLOON, FPL SVENNERHOLM, AM HOLMGREN, J AF CLEMENS, J SACK, D RAO, M CHAKRABORTY, J KAY, B AHMED, F KHAN, MR VANLOON, FPL SVENNERHOLM, AM HOLMGREN, J TI THE DESIGN AND ANALYSIS OF CHOLERA VACCINE TRIALS - RECENT LESSONS FROM BANGLADESH SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article ID FIELD TRIAL; VIBRIO-CHOLERAE; LATIN-AMERICA; FOLLOW-UP; B-SUBUNIT; EPIDEMIC; RISK AB The recent spread of cholera to Latin America, together with the persistent burden of this disease in Asia and Africa, have stimulated efforts to evaluate new cholera vaccines in field settings. Although the standard experimental paradigm for vaccine field trials is well established, the success of these trials will also depend on suitable consideration of the epidemiology of cholera and of cholera vaccination in the settings under study. Epidemiological studies done in Bangladesh emphasize the importance of appreciating the poorly predictable, multifocal occurrence of cholera in estimating a probable incidence of cholera for a field trial. They also underscore how the filtering effect of enrolling subjects into a prospective trial can dramatically reduce the available population for study, and can yield a study sample whose expected risk of cholera differs markedly from that for the source population. Finally, the data highlight the subtle effects that the mode of surveillance and the choice of an outcome definition can have upon protective efficacy, and emphasize the need for subgroup analyses that address the distinctive variations in vaccine protection that may occur in subjects differing in age and in ABO blood groups, and in subjects exposed to classical versus El Tor cholera. C1 INT CTR DIARRHOEAL DIS RES,BANGLADESH,BANGLADESH. JOHNS HOPKINS UNIV,SCH PUBL HLTH,BALTIMORE,MD 21218. GOTHENBURG UNIV,S-41124 GOTHENBURG,SWEDEN. CTR DIS CONTROL,ATLANTA,GA 30333. RP CLEMENS, J (reprint author), NICHHD,DIV EPIDEMIOL STATS & PREVENT RES,G100 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 20 TC 10 Z9 10 U1 3 U2 4 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD AUG PY 1993 VL 22 IS 4 BP 724 EP 730 DI 10.1093/ije/22.4.724 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA LU482 UT WOS:A1993LU48200023 PM 8225749 ER PT J AU FONTVIEILLE, AM KRISKA, A RAVUSSIN, E AF FONTVIEILLE, AM KRISKA, A RAVUSSIN, E TI DECREASED PHYSICAL-ACTIVITY IN PIMA INDIAN COMPARED WITH CAUCASIAN CHILDREN SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE BODY COMPOSITION; FAT DISTRIBUTION; PHYSICAL ACTIVITY QUESTIONNAIRE ID BODY-COMPOSITION; RISK-FACTORS; EXPENDITURE; OBESITY AB Since reduced physical activity might be a risk factor for body weight gain, we studied the relationship between physical activity and body composition in 43 Pima Indian children (22 male/21 female, mean +/- s.d.: 9.9 +/- 1.1 years) and 42 Caucasian children (21 male/21 female, 9.7 +/- 1.2 years). A list of usual sport leisure activities was established (e.g. bicycling, swimming, basketball) and the subjects were asked how much time they had devoted to each activity over the past week and the last year. Data on time spent playing outside (excluding sport leisure activities for the estimation of physical activity) and watching television/videos were also collected. Pima Indians were taller (143 +/- 9 vs. 137 +/- 8 cm, P < 0.001), heavier (48.6 +/- 15.8 vs. 32.9 +/- 7.8 kg, P < 0.0001) and fatter (39 +/- 16 vs. 24 +/- 7% fat, P < 0.001) than Caucasians. Pima Indian girls showed significantly lower past year and past week sport leisure activity than Caucasian girls (P < 0.01) and spent significantly more time watching television/videos (P < 0.05). Pima boys also showed significantly lower past week sport leisure activity than Caucasian boys (P < 0.05). In Pima Indian boys, past year sport leisure activity correlated negatively (P < 0.05) with body mass index (r = -0.49) and percentage body fat (r = -0.56). However, such correlations were not found in Pima Indian girls, possibly due their very low levels of activity. Even though cause and effect cannot be distinguished in cross-sectional studies, these findings suggest that decreased physical activity and increased television viewing may contribute to the development of obesity in Pima Indian children. C1 UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT EPIDEMIOL,PITTSBURGH,PA 15261. RP FONTVIEILLE, AM (reprint author), NIDDKD,CLIN DIABET & NUTR SECT,4212 N 16TH ST,ROOM 541,PHOENIX,AZ 85016, USA. NR 23 TC 68 Z9 67 U1 1 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD AUG PY 1993 VL 17 IS 8 BP 445 EP 452 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA LP911 UT WOS:A1993LP91100004 PM 8401746 ER PT J AU CHOCHUNG, YS AF CHOCHUNG, YS TI DIFFERENTIATION THERAPY OF CANCER TARGETING THE RI-ALPHA REGULATORY SUBUNIT OF CAMP-DEPENDENT PROTEIN-KINASE (REVIEW) SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Review DE CAMP-KINASE; ANTISENSE; MALIGNANCY; GROWTH CONTROL ID CYCLIC-AMP ANALOGS; ADENOSINE 3'-5'-CYCLIC MONOPHOSPHATE; TISSUE-SPECIFIC EXTINGUISHER; HL-60 LEUKEMIA-CELLS; AMINO-ACID-SEQUENCE; ANTISENSE OLIGODEOXYNUCLEOTIDE; GENE-TRANSCRIPTION; RECEPTOR PROTEINS; BINDING-SITES; GROWTH-FACTOR AB Consideration of the cancer process as a problem of blocked ontogeny makes attractive the approach to the control of cancer through differentiation therapy. The use of antisense strategy and retroviral vector-mediated gene transfer technology provided direct evidence that two isoforms of cAMP receptor protein, the RI and RII regulatory subunits of cAMP-dependent protein kinase, have opposite, roles in cell growth and differentiation, RI being growth stimulatory while RII is a growth-inhibitory and differentiation-inducing protein. As RIalpha expression is enhanced during cell transformation, and in primary human tumors and cancer cell lines as compared to their normal counterparts, it is an attractive target for cancer treatment. 8-Cl-cAMP and RIalpha antisense oligodeoxynucleotide, those that effectively down-regulate RIalpha and upregulate RIIbeta without producing cytotoxicity, provide new approaches toward differentiation therapy of cancer. RP CHOCHUNG, YS (reprint author), NCI,TUMOR IMMUNOL & BIOL LAB,CELLULAR BIOCHEM SECT,BLDG 10,ROOM 5B38,BETHESDA,MD 20892, USA. NR 86 TC 9 Z9 9 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 AUG PY 1993 VL 3 IS 2 BP 141 EP 148 PG 8 WC Oncology SC Oncology GA LP940 UT WOS:A1993LP94000002 PM 21573339 ER PT J AU KONDOH, N SCHWEINFEST, CW PAPAS, TS AF KONDOH, N SCHWEINFEST, CW PAPAS, TS TI CHROMOSOMAL ALTERATIONS IN PERMANENTLY DIFFERENTIATED HT29 COLON-CARCINOMA CELLS INDUCED WITH SODIUM-BUTYRATE SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE HT29 CELLS; SODIUM BUTYRATE; DIFFERENTIATION; TUMORIGENICITY; KARYOTYPE ANALYSIS ID ENTEROCYTIC DIFFERENTIATION; LINE; HT-29; GROWTH; SENSITIVITY; ADAPTATION; EXPRESSION; ONCOGENE; ANTIGEN; GLUCOSE AB We have established differentiated subclones from sodium butyrate-treated HT29 colon carcinoma cells. Two subclones, CIII and CVII, grew as tightly-compacted colonies and showed polarized confluent monolayers in vitro. CIII cells formed domes in vitro, a morphological characteristic of columnar absorptive epithelium. Besides these differentiated characteristics, CIII and CVII cells showed lower tumorigenicity than parental HT29 cells. Karyotypic analysis indicated that all cells retained chromosomes in the triploid range. However, modal chromosome numbers among 30 metaphases of each clone were concomitantly reduced from 71 (in HT29) to 68 (in CVII) or 67 (in CHI) with the differentiated phenotypes. Our preliminary karyotype analysis has suggested that the number of chromosomes 10q21-qter, 14q22-qter and 16q were decreased in both subclones. To confirm this, DNAs from these cells and another butyrate-induced subclone, CI-1, were analyzed with several DNA markers. Southern blot analysis indicated that parental HT29 cells were polymorphic for the BamHI and TaqI RFLPs detected by urokinase (7 kbp and 1.6 kbp) and D10S25 (2.5 kbp and 2.1 kbp) probes, respectively, both of which are located on chromosome band 10q. In CI-1 and CVII cells, allelic losses of urokinase (1.6 kbp) and D10S25 (2.5 kbp) were observed, respectively. Although both alleles of these markers were conserved in CIII cells, one allele of urokinase (7 kbp) and D10S25 (2.1 kbp) was less representative. Southern blot analysis using probes for Fos proto-oncogene, D14S20 marker type IV collagenase gene, haptoglobin gene located on chromosome bands 14q and 16q did not show any loss or rearrangement occurred in these subclones. Similarly, no loss or rearrangement was observed for the krev-1 gene on chromosome 1, whose number was not changed in either subclone. These findings indicate that in CI- 1, CIII, and CVII cells, the number of chromosome band 10q is decreased relative to HT29 cells. These deletions may be implicated in the morphological differentiation of HT29 cells treated with sodium butyrate. RP KONDOH, N (reprint author), NCI,FCRDC,MOLEC ONCOL LAB,POB B,BLDG 469,RM 205,FREDERICK,MD 21702, USA. NR 30 TC 2 Z9 2 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 AUG PY 1993 VL 3 IS 2 BP 177 EP 183 PG 7 WC Oncology SC Oncology GA LP940 UT WOS:A1993LP94000008 PM 21573345 ER PT J AU PARKER, RJ DIMERY, IW DABHOLKAR, M VIONNET, J REED, E AF PARKER, RJ DIMERY, IW DABHOLKAR, M VIONNET, J REED, E TI PLATINUM-DNA ADDUCT IN HEAD AND NECK-CANCER PATIENTS RECEIVING CISPLATIN AND CARBOPLATIN CHEMOTHERAPY SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE CISPLATIN; CARBOPLATIN; DNA ADDUCT; HEAD AND NECK CANCER ID LEUKOCYTE DNA; SPECTROMETRY; QUANTITATION; REPAIR; CELLS AB Sixteen patients with squamous cell carcinoma of the head and neck region were studied for the formation of platinum-DNA adduct in leukocyte DNA. Every patient received carboplatin and cisplatin, each given intravenously on day 1 of 21-day treatment cycles. Blood was obtained for DNA isolation 24 hours after treatment on cycles 1 and 2; and on the morning before cycle 2 of therapy (21 days after cycle 1 drug delivery). Adduct was measured by atomic absorbance spectrometry with Zeeman background correction. As has been shown in previous studies, adduct persistence and accumulation could be demonstrated in a portion of the cohort. Adduct removal from blood cell DNA during the 21 days of cycle number 1, was determined for 12 patients. In these patients, adduct removal was directly i-elated to clinical resistance to the cisplatin/carboplatin treatment regimen; and adduct removal was inversely related to leukocyte toxicity. These data demonstrate that changes in adduct levels with time may provide valuable information, in the study of the human in vivo biology of platinum-DNA damage and repair. C1 NCI,MED BRANCH,MED OVARIAN CANC SECT,BLDG 10,ROOM 12N226,BETHESDA,MD 20892. MD ANDERSON CANC CTR,HEAD NECK & THORAC MED ONCOL SECT,HOUSTON,TX. NR 17 TC 15 Z9 15 U1 0 U2 1 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD AUG PY 1993 VL 3 IS 2 BP 331 EP 335 PG 5 WC Oncology SC Oncology GA LP940 UT WOS:A1993LP94000032 PM 21573369 ER PT J AU KAFADAR, K TUKEY, JW AF KAFADAR, K TUKEY, JW TI UNITED-STATES CANCER DEATH RATES - A SIMPLE ADJUSTMENT FOR URBANIZATION SO INTERNATIONAL STATISTICAL REVIEW LA English DT Article DE ADJUSTMENT; CANCER; DEATH RATES; MEASURES OF URBANIZATION; RESIDUALS AFTER ADJUSTMENT; SIZES OF LARGEST PLACES; SMOOTHING ID MORTALITY-RATES; LUNG-CANCER; GEOGRAPHIC PATTERNS; AIR-POLLUTION; MODELS; URBAN AB A statistical study of death rates due to various forms of cancer in the United States begins with an adjustment of the rates in terms of a measure of urbanization. The rates used in this study were collected and age-adjusted by the National Cancer Institute (NCI); they cover the years 1950-1969. Only the rates for trachea, bronchus and lung combined are analyzed here. The county rates are analyzed separately for each of five disk-shaped regions of the country, selected to cover most areas with relatively high rates. A measure of urbanization based on the size of the largest place in the county is defined and then used to stratify the counties in each disk. Considering first only Poisson variation, Poisson intervals for the stratum rates in each disk are derived and compared across regions. The analysis, largely exploratory in nature, is a first step. When continued, it should provide insights about geographic gradations that might later prove to be related to environmental influences. This study treats only the rates from cancer of the trachea, bronchus and lung, for white males in selected parts of the country, but it is clear that the methodology may be applied to other sites, populations, or areas. C1 PRINCETON UNIV, PRINCETON, NJ 08544 USA. RP KAFADAR, K (reprint author), NCI, DIV CANC PREVENT & CONTROL, BIOMETRY BRANCH, BETHESDA, MD 20892 USA. NR 41 TC 8 Z9 8 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0306-7734 EI 1751-5823 J9 INT STAT REV JI Int. Stat. Rev. PD AUG PY 1993 VL 61 IS 2 BP 257 EP 281 DI 10.2307/1403628 PG 25 WC Statistics & Probability SC Mathematics GA LV172 UT WOS:A1993LV17200006 PM 12179586 ER PT J AU BAREZ, S BOUMPAS, DT PERCOPO, CM ANASTASSIOU, ED HOOKS, JJ DETRICK, B AF BAREZ, S BOUMPAS, DT PERCOPO, CM ANASTASSIOU, ED HOOKS, JJ DETRICK, B TI MODULATION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-1 GENES IN HUMAN RETINOBLASTOMA CELLS BY INTERFERONS SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MYC MESSENGER-RNA; CLASS-I GENE; DAUDI CELLS; IFN-GAMMA; ANTIGEN EXPRESSION; CONSENSUS SEQUENCE; NEURO-BLASTOMA; PROTEIN; ALPHA; TRANSCRIPTION AB Purpose. To examine the mechanism(s) of interferon (IFN) induced expression of major histocompatibility complex (MHC) class 1 molecules on the human retinoblastoma cell line, Y-79. Methods. Y-79 cells were incubated in the presence of IFN-alpha, -beta, and -gamma. Y-79 cell expression of MHC class 1 molecules was measured by flow cytometric analysis. HLA-B7 and oncogene transcription were evaluated by Northern blot analysis and nuclear runoff transcription assays. Results. IFN-gamma increased MHC-class 1 antigen expression and induced a fivefold increase in its transcription rate. Posttranscriptionally, IFN-beta and -gamma increased steady state messenger RNA for the HLA-B7 gene. These effects were not associated with down regulation of N-myc oncogene nuclear transcription. Moreover, dexamethasone did not affect the IFN-gamma induced expression of MHC-class 1 molecules. Conclusions. Both transcriptional and posttranscriptional mechanisms are implicated in the modulation of class 1 molecule expression by IFN. In addition, this modulation is not associated with down regulation of N-myc oncogene expression. Spontaneous or IFN-gamma induced MHC class 1 antigen expression in retinoblastoma Y-79 cells is resistant to glucocorticoid hormones. C1 NEI,IMMUNOL LAB,IMMUNOL & VIROL SECT,BLDG 10,ROOM 6N228,BETHESDA,MD 20892. NIDDKD,KIDNEY DIS SECT,BETHESDA,MD. GEORGETOWN UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20007. NR 40 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 AUG PY 1993 VL 34 IS 9 BP 2613 EP 2621 PG 9 WC Ophthalmology SC Ophthalmology GA LR387 UT WOS:A1993LR38700003 PM 7688356 ER PT J AU URBA, WJ LONGO, DL AF URBA, WJ LONGO, DL TI HODGKINS-DISEASE IN ADULTS .1. SO INVESTIGATIVE RADIOLOGY LA English DT Review ID REED-STERNBERG CELLS; EPSTEIN-BARR-VIRUS; EXTENDED-FIELD RADIOTHERAPY; COMBINED MODALITY THERAPY; CHEMOTHERAPY PLUS RADIOTHERAPY; CLINICAL STAGE-I; PROGNOSTIC FACTORS; COMBINATION CHEMOTHERAPY; RADIATION-THERAPY; MOPP CHEMOTHERAPY RP URBA, WJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702, USA. NR 150 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD AUG PY 1993 VL 28 IS 8 BP 737 EP 752 DI 10.1097/00004424-199308000-00017 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LR618 UT WOS:A1993LR61800013 PM 8376007 ER PT J AU BRODER, S AF BRODER, S TI PERSPECTIVES ON CANCER IN JAPAN AND THE UNITED-STATES SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Editorial Material RP BRODER, S (reprint author), NCI,BETHESDA,MD 20892, USA. NR 15 TC 24 Z9 24 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 AUG PY 1993 VL 84 IS 8 BP 821 EP 830 PG 10 WC Oncology SC Oncology GA LU656 UT WOS:A1993LU65600002 PM 8407543 ER PT J AU HARRIS, CC SUEMASU, K SKINNER, DB WATANABE, H KAKIZOE, T AF HARRIS, CC SUEMASU, K SKINNER, DB WATANABE, H KAKIZOE, T TI REPORT OF THE 6TH INTERNATIONAL-SYMPOSIUM OF THE FOUNDATION-FOR-THE-PROMOTION-OF-CANCER-RESEARCH - FUNDAMENTAL AND CLINICAL RESEARCH IN ESOPHAGEAL CANCER SO JAPANESE JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material C1 NCI,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU FOUNDATION PROMOTION CANCER RESEARCH PI TOKYO PA NATL CANCER CENTER HOSPITAL 1-1 TSUKIJI 5-CHOME CHUO-KU, TOKYO 104, JAPAN SN 0368-2811 J9 JPN J CLIN ONCOL JI Jpn. J. Clin. Oncol. PD AUG PY 1993 VL 23 IS 4 BP 263 EP 272 PG 10 WC Oncology SC Oncology GA MA743 UT WOS:A1993MA74300009 PM 8105120 ER PT J AU ATKINS, MS STOFF, DM OSBORNE, ML BROWN, K AF ATKINS, MS STOFF, DM OSBORNE, ML BROWN, K TI DISTINGUISHING INSTRUMENTAL AND HOSTILE AGGRESSION - DOES IT MAKE A DIFFERENCE SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article ID ATTENTION; HYPERACTIVITY; IMPULSIVITY; DISORDER; HUMANS AB An analogue task of instrumental and hostile aggression during a competitive game, modified to minimize overlap between aggressive responses, was evaluated in 8- to 14-year-old clinically referred boys (n = 33). Postgame interviews indicated that the hostile response, an aversive noise, was perceived by over 80% of subjects as hostile and not instrumental. In contrast, the instrumental response, blocking the opponent's game, was perceived about equally as having instrumental and hostile functions. The hostile aggressive response was uniquely correlated with continuous performance task impulsive commission errors (r = .51), which supported the theoretical relation of hostile aggression to poor impulse control. These results suggest that instrumental and hostile aggression can be distinguished and when precisely defined are distinct in theoretically important ways. C1 UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. NIMH,BETHESDA,MD 20892. FU BHP HRSA HHS [NICHD DH26979]; NIMH NIH HHS [NIMH MH4682, NIMH MH40364] NR 22 TC 37 Z9 37 U1 2 U2 6 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 AUG PY 1993 VL 21 IS 4 BP 355 EP 365 DI 10.1007/BF01261598 PG 11 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA LR772 UT WOS:A1993LR77200001 PM 8408984 ER PT J AU HEALEY, JM NEWCORN, JH HALPERIN, JM WOLF, LE PASCUALVACA, DM SCHMEIDLER, J OBRIEN, JD AF HEALEY, JM NEWCORN, JH HALPERIN, JM WOLF, LE PASCUALVACA, DM SCHMEIDLER, J OBRIEN, JD TI THE FACTOR STRUCTURE OF ADHD ITEMS IN DSM-III-R - INTERNAL CONSISTENCY AND EXTERNAL VALIDATION SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article ID ATTENTION DEFICIT DISORDER; TEACHER RATINGS; IMPULSIVITY; HYPERACTIVITY; DIMENSIONS; VALIDITY; SYMPTOMS; CHILDREN; PARENT AB Previous research employing factor-analytic procedures to study the underlying dimensions of DSM-III attention deficit disorder with hyperactivity (ADDH) symptoms have consistently supported a two-factor model. Revision of the structure of the ADHD diagnosis in DSM-III-R, as well as inclusion of new items, has raised the question of comparability of the two diagnoses. To explore the significance of these changes, teacher ratings of DSM-III ADDH items and DSM-III-R ADHD items of 85 nonreferred school children were factor-analyzed to determine their underlying factor structures. A similar two-factor solution was obtained for each. diagnostic scale. The factors consisted of items believed to reflect inattention and hyperactivity-impulsivity constructs. These factors were further evaluated against results of a cognitive test battery to ascertain whether objective, external validation could be demonstrated. The hyperactivity-impulsivity factor scores were related to continuous performance test measures of response inhibition, while inattention-disorganization factor scores were related to measures of attention and visual search. Implications for assessment and diagnosis of ADHD are discussed. C1 CUNY MT SINAI SCH MED,DEPT PSYCHIAT,NEW YORK,NY 10029. CUNY QUEENS COLL,DEPT PSYCHOL,FLUSHING,NY 11367. ELMHURST HOSP,DEPT PSYCHIAT,ELMHURST,IL. NIMH,BETHESDA,MD 20892. OI Newcorn, Jeffrey /0000-0001-8993-9337 NR 22 TC 36 Z9 36 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0091-0627 J9 J ABNORM CHILD PSYCH JI J. Abnorm. Child Psychol. PD AUG PY 1993 VL 21 IS 4 BP 441 EP 453 DI 10.1007/BF01261603 PG 13 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA LR772 UT WOS:A1993LR77200006 PM 8408989 ER PT J AU WHANGPENG, J CHEN, YMA KNUTSEN, T ZHAO, WP TSAI, S AF WHANGPENG, J CHEN, YMA KNUTSEN, T ZHAO, WP TSAI, S TI CHROMOSOME-STUDIES IN HTLV-I, HTLV-II, AND HIV-1, HIV-2 CELL-LINES INFECTED IN-VIVO AND IN-VITRO SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HTLV-I HTLV-II; HIV-1; HIV-2; CHROMOSOMAL ABNORMALITIES; CYTOGENETIC ANALYSIS ID LEUKEMIA LYMPHOMA VIRUS; PNEUMOCYSTIS-CARINII PNEUMONIA; LYMPHOCYTES; AIDS; RETROVIRUSES AB HTLV-I, II and HIV-1, 2 are T-cell tropic viruses, all belonging to the retrovirus family. These viruses are transmitted horizontally by intimate contact or through blood products. The study of chromosomal changes in these T cells may enhance our understanding of the nature and mechanism of these viral infections. However, because of the cytopathic effect of these viruses on T cells, the direct observation of abnormalities in these cells is sometimes difficult. We performed chromosomal analysis on six HTLV-I cell lines from patients with HTLV-I-positive leukemia/lymphoma, one HTLV-I variant cell line, and two HTLV-II-positive cell lines. The results of these studies were compared with the findings in an earlier (published) study of direct preparations and short-term cultures of cells from 11 HTLV-I-positive NIH patients. Our study also included cytogenetic analysis of seven established cell lines and six normal peripheral bloods infected in vitro with the HTLV-III(B) strain of HIV-1 (five cell lines and six bloods) or HIV-2 (two lines); all were studied both before and after viral infection. The results showed that all six HTLV-1 cell lines and the variant cell line had multiple chromosomal changes: three lines had deletions of chromosome 6, with breakpoints between q21 and q25. Nine of the 11 NIH patients with HTLV-1 had clonal abnormalities, and six of these nine had chromosome 6 deletions with breakpoints ranging from band q11 to band q23. The high incidence of 6q involvement may be of considerable significance in this clinical subgroup of HTLV-1 patients. The two HTLV-II cell lines were established from patients suffering from HTLV-II infection. Both of these cell lines had translocations of chromosome 21 at p11, and both had extra copies of chromosome 20; no known oncogenes or receptors are located on these two chromosomes. Chromosome 17 was the chromosome most frequently involved (three lines) in the five HIV-1-infected cell lines, followed by chromosomes 3 and 21; it is of interest that NGL (also known as C-ERBB2 or NEU oncogene), CD7 (a lymphocyte antigen), HTLV-1 receptor, NGFR (nerve growth factor receptor), and MIC6 are all cell surface antigens coded by genes on chromosome 17q. No specific chromosome abnormalities were found in the normal blood samples infected with HIV-1, and no unique chromosome changes were noted in the two cell lines infected with HIV-2; however, the infected H9 line had a chromosome 17 abnormality, a translocation involving band 17p11. C1 NCI,MED BRANCH,BETHESDA,MD 20892. ACAD SINICA,TAIPEI 115,TAIWAN. WALTER REED ARMY MED CTR,ARMED FORCES INST PATHOL,WASHINGTON,DC 20307. NR 32 TC 3 Z9 3 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 AUG PY 1993 VL 6 IS 8 BP 930 EP 940 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LM633 UT WOS:A1993LM63300011 PM 8315577 ER PT J AU WHITE, MV AF WHITE, MV TI NASAL CHOLINERGIC HYPERRESPONSIVENESS IN ATOPIC SUBJECTS STUDIED OUT-OF-SEASON SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE NASAL GLANDULAR HYPERRESPONSIVENESS; METHACHOLINE; LACTOFERRIN; ALBUMIN; CHOLINERGIC STIMULATION ID PATHO-PHYSIOLOGY; NERVOUS-SYSTEM; HISTAMINE; RESPONSES; RESPONSIVENESS; METHACHOLINE; SECRETIONS; RHINITIS; HYPERREACTIVITY; INCREASES AB Background: Atopic individuals have previously been shown to have an autonomic imbalance consisting of heightened cholinergic responsiveness in the lung, skin, and eyes, and beta-adrenergic hyporesponsiveness in the lungs, eyes, and vasculature. This array of abnormalities is often accompanied by nonspecific bronchial hyperresponsiveness, as well as alpha-adrenergic hyperresponsiveness in individuals with asthma. Methods: To determine whether atopic individuals have intrinsic nasal airway hyperresponsiveness to methacholine, 21 nonatopic subjects and 37 subjects with allergic rhinitis were studied. All subjects were studied out of their allergy seasons, and all allergy-related medications were discontinued before the study began. Subjects underwent nasal challenge with methacholine (1 to 25 mg), and lavaged nasal secretions were analyzed for total protein, the plasma marker albumin, and the glandular marker lactoferrin. Results: Atopic subjects demonstrated increased glandular responsiveness to methacholine as evidenced by an increase in the secretion of lactoferrin in response to individual doses of methacholine. Although the maximal lactoferrin secretion did not increase, glandular sensitivity to methacholine was heightened because the dose of methacholine required to induce lactoferrin secretion achievable by 60% of the study population was significantly lower in the atopic group. The volume of lavaged secretions recovered and congestion scores were also higher in the atopic group as compared with the normal control group. Conclusions: These data strongly suggest that atopic individuals have intrinsic nasal glandular hyperresponsiveness to cholinergic stimulation. C1 NIAID,ALLERG DIS SECT,BETHESDA,MD 20892. NR 28 TC 21 Z9 21 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD AUG PY 1993 VL 92 IS 2 BP 278 EP 287 DI 10.1016/0091-6749(93)90171-B PG 10 WC Allergy; Immunology SC Allergy; Immunology GA LT469 UT WOS:A1993LT46900008 PM 8349938 ER PT J AU FLEG, JL SCHULMAN, SP GERSTENBLITH, G BECKER, LC OCONNOR, FC LAKATTA, EG AF FLEG, JL SCHULMAN, SP GERSTENBLITH, G BECKER, LC OCONNOR, FC LAKATTA, EG TI ADDITIVE EFFECTS OF AGE AND SILENT-MYOCARDIAL-ISCHEMIA ON THE LEFT-VENTRICULAR RESPONSE TO UPRIGHT CYCLE EXERCISE SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE SILENT ISCHEMIA; LEFT VENTRICLE ID CORONARY-ARTERY DISEASE; EJECTION FRACTION; HEART-RATE; VOLUME; DYSFUNCTION; DECREASE; SEX AB To separate the independent effects of age and silent myocardial ischemia on the left ventricular response to aerobic exercise, maximal upright cycle ergometry was performed in three groups: 8 clinically healthy older men [76 +/- 3 (SE) yr] with ischemic electrocardiogram (ECG) and TI scan responses to prior maximal treadmill exercise (old silent ischemic subjects), 16 age-matched men with normal ECG and TI scan responses (old controls), and 21 healthy young (33 +/- 1 yr) men (young controls). Although the left ventricular ejection fraction, end-diastolic volume index, and end-systolic volume index were similar in the three groups at rest, with increasing work loads there was a progressive increase in the end-diastolic volume index and a blunted decline in end-systolic volume index in the two older groups, which was most apparent in the old silent ischemic subjects. Thus, at peak effort, end-diastolic volume index was largest in old silent ischemic subjects (101 +/- 6 ml/m2), intermediate in old controls (85 +/- 6 ml/m2), and smallest in young controls (67 +/- 3 ml/m2) (P < 0.002); conversely, left ventricular ejection fraction was highest in young controls (85 +/- 2), intermediate in old controls (76 +/- 3), and lowest in the old silent ischemic group (66 +/- 2) (P < 0.001). At exhaustion the peak systolic pressure-end-systolic volume index was significantly lower in the silent ischemic group than in young controls (6 +/- 1 vs. 25 +/- 4 mmHg . ml-1. m-2, respectively; P < 0.001) with the old controls in between (16 +/- 5 mmHg . ml-1 . m-2). Thus the diminished aerobic capacity, cardiac dilatation, and blunted ejection fraction response to upright cycle ergometry associated with normative aging are exaggerated in asymptomatic older men with exercise-induced silent myocardial ischemia. C1 JOHNS HOPKINS UNIV,SCH MED,DIV CARDIOL,BALTIMORE,MD 21215. RP FLEG, JL (reprint author), NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. FU NIA NIH HHS [N01-AG-4-2109] NR 34 TC 9 Z9 10 U1 0 U2 1 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 AUG PY 1993 VL 75 IS 2 BP 499 EP 504 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA LT582 UT WOS:A1993LT58200003 PM 8226445 ER PT J AU GAWIN, AZ BARANIUK, JN IGARASHI, Y KALINER, MA AF GAWIN, AZ BARANIUK, JN IGARASHI, Y KALINER, MA TI EFFECTS OF CAPSAICIN DESENSITIZATION ON NASAL MUCOSAL SECRETION IN GUINEA-PIGS IN-VIVO SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE NASAL MUCOSA; NASAL SECRETION; METHACHOLINE; ATROPINE; NEUROGENIC INFLAMMATION; CAPSAICIN-SENSITIVE NOCICEPTIVE SENSORY NERVES; AXON RESPONSE ID MULTIPLE TACHYKININS; SENSORY NEURONS; SUBSTANCE-P; RHINITIS; STIMULATION; MECHANISMS; EXUDATION; HISTAMINE; DEFENSE; PROTEIN AB Capsaicin-sensitive mechanisms may contribute to histamine's effects on guinea pig nasal mucosal secretion in vivo. Histamine nasal provocations were performed, secretions were collected, and the following variables were measured: total protein (marker of all secretory processes), alkaline phosphatase (marker of glandular secretion), and albumin (marker of vascular permeability, epithelial permeability, and glandular transport). By challenging only one nostril (ipsilateral), the contralateral responses to these challenges were examined and the nature of ''nasonasal'' reflexes was determined. Histamine increased albumin and alkaline phosphatase concentrations in lavage fluid on the ipsilateral and contralateral sides. The alkaline phosphatase secretion was reduced by atropine. Capsaicin induced dose-dependent albumin exudation. To determine the roles of capsaicin-sensitive sensory nerves, one nostril was desensitized by topical application of capsaicin to one nostril in increasing doses daily for 5 wk. This led to 1) ablation of all secretory responses to capsaicin, 2) ablation of histamine-induced alkaline phosphatase and total protein secretion, 3) blunted histamine-induced albumin exudation on the desensitized side, and 4) ablation of histamine-induced contralateral reflex-mediated protein secretion. These results indicate that capsaicin stimulates vascular responses, probably by stimulating nociceptive nerve axon responses. Histamine induces vascular responses and albumin exudation by both capsaicin-sensitive sensory neuron axon responses and direct effects on vessels. Histamine stimulates glandular secretion through a capsaicin-sensitive afferent/cholinergic efferent reflex. C1 GEORGETOWN UNIV, DIV RHEUMATOL IMMUNOL & ALLERGY, GL-020 GORMAN BLDG, WASHINGTON, DC 20007 USA. NIAID, CLIN INVEST LAB, ALLERG DIS SECT, BETHESDA, MD 20892 USA. NR 29 TC 8 Z9 8 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 EI 1522-1601 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD AUG PY 1993 VL 75 IS 2 BP 798 EP 804 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA LT582 UT WOS:A1993LT58200044 PM 8226484 ER PT J AU GILLISSEN, A BIRRER, P MCELVANEY, NG BUHL, R VOGELMEIER, C HOYT, RF HUBBARD, RC CRYSTAL, RG AF GILLISSEN, A BIRRER, P MCELVANEY, NG BUHL, R VOGELMEIER, C HOYT, RF HUBBARD, RC CRYSTAL, RG TI RECOMBINANT SECRETORY LEUKOPROTEASE INHIBITOR AUGMENTS GLUTATHIONE LEVELS IN LUNG EPITHELIAL LINING FLUID SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE ANTIPROTEASES; ANTIOXIDANTS; BRONCHOSCOPY; ANIMAL ID LEUKOCYTE PROTEASE INHIBITOR; LOWER RESPIRATORY-TRACT; ANTINEUTROPHIL ELASTASE DEFENSE; ALPHA-1-ANTITRYPSIN DEFICIENCY; EMPHYSEMA; FIBROSIS; THERAPY; CELLS; STRATEGIES; DEPLETION AB Secretory leukoprotease inhibitor (SLPI), a 12-kDa serine antiprotease, serves as the major inhibitor of neutrophil elastase (NE) on the epithelial surface of the upper airways. As a control for studies to evaluate the aerosol administration of recombinant SLPI (rSLPI) to augment the anti-NE defenses of the lung, the status of antioxidants in respiratory epithelial lining fluid (ELF) was evaluated. Unexpectedly, aerosol administration of rSLPI caused an elevation in ELF glutathione, a major component of the epithelial antioxidant screen; i.e., rSLPI may provide not only augmentation of anti-NE defenses but also antioxidant defenses. To evaluate this concept, rSLPI (100 mg) was aerosolized to sheep, and SLPI, glutathione, anti-NE capacity, and anti-H2O2 Capacity were evaluated in respiratory ELF over a 30-h period. As expected, aerosolization of rSLPI increased ELF SLPI levels and anti-NE capacity. Strikingly, postaerosol levels of glutathione in ELF were also increased (5-fold 24 h after aerosol), with a concomitant increase in ELF anti-H2O2 capacity; i.e., the rSLPI augmented the antioxidant screen of ELF. This suggests that rSLPI may be particularly well suited for therapy in lung diseases characterized by excess of both serine proteases and oxidants on the respiratory epithelial surface. C1 NHLBI,PULM BRANCH,BLDG 10,RM 6D03,BETHESDA,MD 20892. NHLBI,LAB ANIM MED & SURG SECT,BETHESDA,MD 20892. RI McElvaney, Noel/A-6809-2010 NR 38 TC 47 Z9 48 U1 0 U2 1 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 AUG PY 1993 VL 75 IS 2 BP 825 EP 832 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA LT582 UT WOS:A1993LT58200048 PM 7901193 ER PT J AU JARVIK, M KILLEN, JD VARADY, A FORTMANN, SP AF JARVIK, M KILLEN, JD VARADY, A FORTMANN, SP TI THE FAVORITE CIGARETTE OF THE DAY SO JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE POSTPRANDIAL SMOKING; NICOTINE DEPENDENCY; MORNING CIGARETTE ID TOLERANCE QUESTIONNAIRE; RELAPSE PREVENTION; NICOTINE; SMOKING; DEPENDENCE; EXPOSURE AB The choice of a favorite cigarette smoked during a given day varies considerably. Preferences are related to nicotine dependence and the lifestyles of smokers. In a sample of 5124 smokers, the ''after-dinner cigarette'' was chosen as the cigarette which they would miss most, while the next largest proportion of smokers (33%) said that they would miss the ''first cigarette of the morning'' most. The latter group scored highest on tests of nicotine dependence. In contrast, infrequent smokers (''chippers'') chose the after-dinner cigarette. C1 STANFORD UNIV,SCH MED,CTR RES DIS PREVENT,PALO ALTO,CA 94304. NATL INST CHILD HLTH & HUMAN DEV,ROCKVILLE,MD. RP JARVIK, M (reprint author), VET ADM MED CTR,PSYCHOPHARMACOL UNIT 691-B151D,LOS ANGELES,CA 94304, USA. FU NHLBI NIH HHS [HL39770] NR 17 TC 16 Z9 16 U1 0 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0160-7715 J9 J BEHAV MED JI J. Behav. Med. PD AUG PY 1993 VL 16 IS 4 BP 413 EP 422 DI 10.1007/BF00844781 PG 10 WC Psychology, Clinical SC Psychology GA LV628 UT WOS:A1993LV62800006 PM 8411146 ER PT J AU FOX, KM MAGAZINER, J SHERWIN, R SCOTT, JC PLATO, CC NEVITT, M CUMMINGS, S AF FOX, KM MAGAZINER, J SHERWIN, R SCOTT, JC PLATO, CC NEVITT, M CUMMINGS, S TI REPRODUCTIVE CORRELATES OF BONE MASS IN ELDERLY WOMEN SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID PHYSICAL-ACTIVITY; MINERAL DENSITY; CALCIUM INTAKE; OSTEOPOROSIS; LACTATION; PREGNANCY; FOREARM; RISK; DETERMINANTS; PREVENTION AB Results from previous studies of reproductive factors and bone density have been conflicting; some demonstrate a beneficial effect, but others show a detrimental effect on bone density. The present study investigates the association of parity, lactation, and menstruation with radial bone density in 2230 white women, 65 years of age and older. Bone density was assessed by single-photon absorptiometry. Linear multiple regression was utilized to determine if reproductive factors were associated with radial bone density. The number of births, duration of menstrual bleeding, age at menarche, and years menstruating were significant independent predictors of postmenopausal bone density of the radius. A 1.4% increase in distal radius bone density was observed with each additional birth. Women who began menstruation at age 9 had 6.3% higher bone density than women who began at age 16. Women who menstruated for 3 days during each menstrual cycle had 2.8% less distal radius bone density than women who bled for 7 days. Each decade of menstruation was associated with a 2% greater distal radius bone density. No difference in bone density was demonstrated for women who breast-fed and women who did not. Length of the menstrual cycle, amount of menstrual flow, and irregularity of the menstrual cycle were not significantly associated with radial bone mineral density. In conclusion, pregnancy and menstruation are associated with postmenopausal bone density of the radius. C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. UNIV CALIF SAN FRANCISCO,PREVENT SCI GRP,SAN FRANCISCO,CA 94143. RP FOX, KM (reprint author), UNIV MARYLAND,SCH MED,DEPT EPIDEMIOL & PREVENT MED,660 W REDWOOD ST,BALTIMORE,MD 21201, USA. FU NIA NIH HHS [1-R01-AG05407, 5-R01-AG-05394]; NIAMS NIH HHS [1-R01-AR35585] NR 53 TC 136 Z9 137 U1 1 U2 2 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1993 VL 8 IS 8 BP 901 EP 908 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LN799 UT WOS:A1993LN79900001 PM 8213252 ER PT J AU MINTZ, KP GRZESIK, WJ MIDURA, RJ ROBEY, PG TERMINE, JD FISHER, LW AF MINTZ, KP GRZESIK, WJ MIDURA, RJ ROBEY, PG TERMINE, JD FISHER, LW TI PURIFICATION AND FRAGMENTATION OF NONDENATURED BONE SIALOPROTEIN - EVIDENCE FOR A CRYPTIC, RGD-RESISTANT CELL ATTACHMENT DOMAIN SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID MATRIX GLA PROTEIN; RECOGNITION SITE; FIBROBLAST ATTACHMENT; EXTRACELLULAR-MATRIX; PLATELET RECEPTOR; MESSENGER-RNA; FIBRONECTIN; EXPRESSION; SEQUENCE; BINDING AB Bone sialoprotein (BSP), a small (approximately 80,000 M(r)) integrin binding, RGD-containing bone matrix glycoprotein, has been purified in milligram quantities from the serum-free medium of the rat osteosarcoma cell line UMR-106-BSP using nondenaturing conditions. Routine protein purification without serine protease inhibitors or reducing agents consistently resulted in three major fragments. The largest fragment (El) started at amino add 117 and did not bind to antibodies made to the RGD region of the protein. Furthermore, the smallest fragment (E3), was shown by sequencing to contain the RGD region of the protein. Digestion of intact BSP with highly purified chymotrypsin also resulted in a large fragment (Cl) with properties nearly identical to those of El. The large, non-RGD-containing fragments, El and Cl, as well as the intact BSP, supported attachment by normal human bone cells and human skin fibroblasts in vitro. Attachment to the intact BSP was totally blocked by 0.4 mM GRGDS peptide. Both preparations of skin fibroblasts and approximately half of the preparations of normal human bone cells, however, also would not attach to the El and Cl fragments in the presence of 0.4 mM GRGDS peptide. In contrast, half of the bone cell preparations had significant attachment activity to El (> 50%) and Cl (> 25%) in the presence of 0.4 mM GRGDS peptide. These data suggest that cleavage of the BSP results in either (1) the exposure of a previously unavailable or cryptic cell attachment site or (2) a conformational change that increase the affinity of the complex between a non-RGD-encoded binding region of the El and Cl fragments and at least one receptor. The possible homology of the second, non-RGD-suppressible site of BSP with the second cell attachment site on the gamma chain of fibrinogen is discussed. C1 NIDR,BONE RES BRANCH,ROOM 106,BLDG 30,BETHESDA,MD 20892. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 37 TC 97 Z9 97 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1993 VL 8 IS 8 BP 985 EP 995 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LN799 UT WOS:A1993LN79900011 PM 8213261 ER PT J AU BIANCO, P BRADBEER, JN SILVESTRINI, G RIMINUCCI, M FISHER, LW ROBEY, PG AF BIANCO, P BRADBEER, JN SILVESTRINI, G RIMINUCCI, M FISHER, LW ROBEY, PG TI THE MOLECULAR-ORGANIZATION OF BONE-MATRIX - STRUCTURE AND MODULATED DEPOSITION OF A BONE SIALOPROTEIN-RICH NON-COLLAGEN PHASE SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV ROME,I-00100 ROME,ITALY. NIDR,BETHESDA,MD 20892. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 1 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 AUG PY 1993 VL 8 SU 1 BP S177 EP S177 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500243 ER PT J AU CHEN, P VUKICEVIC, S SAMPATH, TK LUYTEN, FP AF CHEN, P VUKICEVIC, S SAMPATH, TK LUYTEN, FP TI OSTEOGENIC PROTEIN-1 (BONE MORPHOGENETIC PROTEIN-7) PROMOTES MATURATION OF CHICK STERNAL CHONDROCYTES SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. CREAT BIOMOLECULES INC,HOPKINTON,MA 01748. MED SCH ZAGREB,DEPT ANAT,ZAGREB,CROATIA. NR 0 TC 0 Z9 0 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 AUG PY 1993 VL 8 SU 1 BP S317 EP S317 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500799 ER PT J AU CROSS, N ALLEN, S VIEIRA, N HILLMAN, L AF CROSS, N ALLEN, S VIEIRA, N HILLMAN, L TI SERIAL ASSESSMENT OF VITAMIN-D METABOLITES, PERCENT TRUE CALCIUM-ABSORPTION, RENAL MINERAL EXCRETION, AND BONE ACTIVITY DURING PREGNANCY AND LACTATION SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV MISSOURI,COLUMBIA,MO 65201. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 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 AUG PY 1993 VL 8 SU 1 BP S406 EP S406 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20501151 ER PT J AU DING, C LIANG, CT LEVINE, MA AF DING, C LIANG, CT LEVINE, MA TI DOWN-REGULATION OF RENAL PTH RECEPTORS IN AGED RATS IS ASSOCIATED WITH DECREASED LEVELS OF PTH MESSENGER-RNA SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. NR 0 TC 0 Z9 0 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 AUG PY 1993 VL 8 SU 1 BP S185 EP S185 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500273 ER PT J AU FARUP, CE FOX, KM TOBIN, JD EPSTEIN, RS CEJKU, ML PLATO, CC AF FARUP, CE FOX, KM TOBIN, JD EPSTEIN, RS CEJKU, ML PLATO, CC TI CORRELATION OF RADIAL BONE-MINERAL DENSITY AMONG 1ST DEGREE RELATIVES SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV MARYLAND,BALTIMORE,MD 21201. NIA,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 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 AUG PY 1993 VL 8 SU 1 BP S337 EP S337 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500880 ER PT J AU GLOTH, FM TOBIN, JD SMITH, CE HOLLIS, BW AF GLOTH, FM TOBIN, JD SMITH, CE HOLLIS, BW TI BONE-MINERAL DENSITY IS INVERSELY RELATED TO INTACT PARATHYROID-HORMONE LEVELS IN FRAIL HOMEBOUND ELDERLY SUBJECTS WITH A LOW VITAMIN STATUS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. NIA,BETHESDA,MD 20892. MED UNIV S CAROLINA,CHARLESTON,SC 29425. 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 AUG PY 1993 VL 8 SU 1 BP S216 EP S216 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500398 ER PT J AU GRZESIK, WJ SMITH, JW ROBEY, PG AF GRZESIK, WJ SMITH, JW ROBEY, PG TI THE PATTERNS OF INTEGRIN EXPRESSION IN HUMAN DEVELOPING BONE AND IN PRIMARY BONE-CELLS IN-VITRO SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR, BONE RES BRANCH, BETHESDA, MD 20892 USA. SCRIPPS RES INST, LA JOLLA, CA USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 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 AUG PY 1993 VL 8 SU 1 BP S365 EP S365 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500994 ER PT J AU HEEGAARD, AM ROBEY, PG YOUNG, ME AF HEEGAARD, AM ROBEY, PG YOUNG, ME TI CLONING AND CHARACTERIZATION OF UPSTREAM ELEMENTS IN THE HUMAN BIGLYCAN PROMOTER SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BONE RES LAB,BETHESDA,MD 20892. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 1 TC 0 Z9 0 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 AUG PY 1993 VL 8 SU 1 BP S120 EP S120 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500015 ER PT J AU HELDER, M OZKAYNAK, E LUYTEN, FP SAMPATH, TK OPPERMANN, H VUKICEVIC, S AF HELDER, M OZKAYNAK, E LUYTEN, FP SAMPATH, TK OPPERMANN, H VUKICEVIC, S TI COORDINATE EXPRESSION OF OSTEOGENIC PROTEIN-1 (BONE MORPHOGENETIC PROTEIN-7) AND BONE MORPHOGENETIC PROTEIN-3 (OSTEOGENIN) DURING MOUSE AND HUMAN-DEVELOPMENT SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. CREAT BIOMOLECULES INC,HOPKINSON,MA 01748. MED FAC ZAGREB,DEPT ANAT,ZAGREB,CROATIA. NR 0 TC 2 Z9 2 U1 0 U2 3 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 AUG PY 1993 VL 8 SU 1 BP S316 EP S316 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500798 ER PT J AU LOOKER, AC WAHNER, HW DUNN, WL CALVO, MS HARRIS, TB HEYSE, SP JOHNSTON, CC LINDSAY, RL AF LOOKER, AC WAHNER, HW DUNN, WL CALVO, MS HARRIS, TB HEYSE, SP JOHNSTON, CC LINDSAY, RL TI FEMORAL BONE-DENSITY OF UNITED-STATES ADULTS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NCHS,HYATTSVILLE,MD 20782. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. US FDA,WASHINGTON,DC 20204. INDIANA UNIV,INDIANAPOLIS,IN 46223. NIA,BETHESDA,MD 20816. NIAMS,BETHESDA,MD 20892. HELEN HAYES HOSP,W HAVERSTRAW,NY 10993. 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 AUG PY 1993 VL 8 SU 1 BP S336 EP S336 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500876 ER PT J AU QUARTO, R TANAKA, H WILLIAMS, S BARNES, J LIANG, CT AF QUARTO, R TANAKA, H WILLIAMS, S BARNES, J LIANG, CT TI ANALYSIS OF THE BONE-MARROW STROMAL CELLS IN ADULT AND AGED RATS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 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 AUG PY 1993 VL 8 SU 1 BP S283 EP S283 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500663 ER PT J AU SAKAGUCHI, K TAKAGI, Y SHRIVASTAV, S MIKI, T AF SAKAGUCHI, K TAKAGI, Y SHRIVASTAV, S MIKI, T TI MOLECULAR-CLONING AND EXPRESSION OF THE ACIDIC FIBROBLAST GROWTH-FACTOR (FGF) RECEPTORS OF A RAT PARATHYROID CELL-LINE (PT-R) SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIADDKD,METAB DIS BRANCH,BETHESDA,MD 20892. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NR 2 TC 0 Z9 0 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 AUG PY 1993 VL 8 SU 1 BP S173 EP S173 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500225 ER PT J AU SCHIPANI, E WEINSTEIN, LS BERGWITZ, C WHYTE, MP MURRAY, T SCHMIDTKE, J KRONENBERG, HM SEGRE, GV JUPPNER, H AF SCHIPANI, E WEINSTEIN, LS BERGWITZ, C WHYTE, MP MURRAY, T SCHMIDTKE, J KRONENBERG, HM SEGRE, GV JUPPNER, H TI MOLECULAR HETEROGENEITY OF THE PTH/PTHRP RECEPTOR IN PATIENTS WITH PSEUDOHYPOPARATHYROIDISM SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 SHRINERS HOSP CRIPPLED CHILDREN, ST LOUIS, MO USA. MASSACHUSETTS GEN HOSP, DEPT MED, ENDOCRINE UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT PEDIAT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. NIH, BETHESDA, MD 20892 USA. HANNOVER MED SCH, W-3000 HANNOVER 61, GERMANY. ST MICHAELS HOSP, TORONTO M5B 1W8, ONTARIO, CANADA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1993 VL 8 SU 1 BP S132 EP S132 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500061 ER PT J AU SHAPIRO, JR RACHIS, R BELLANTONI, M HARMAN, SM BLACKMAN, MR AF SHAPIRO, JR RACHIS, R BELLANTONI, M HARMAN, SM BLACKMAN, MR TI THE EFFECT OF IGF-I ON SKELETAL TURNOVER IN POSTMENOPAUSAL WOMEN SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,BALTIMORE,MD 21224. NIA,GERONTOL RES CTR,BETHESDA,MD 20892. 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 AUG PY 1993 VL 8 SU 1 BP S327 EP S327 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500841 ER PT J AU SHENKER, A CHANSON, P WEINSTEIN, LS SPIEGEL, AM LOMRI, A MARIE, PJ AF SHENKER, A CHANSON, P WEINSTEIN, LS SPIEGEL, AM LOMRI, A MARIE, PJ TI OSTEOBLASTIC CELLS FROM MONOSTOTIC FIBROUS DYSPLASIA CONTAIN ARG201 MUTATION OF GS(ALPHA) SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDDK,MOLEC PATHOPHYSIOL BRANCH,BETHESDA,MD 20829. HOP LARIBOISIERE,INSERM,U349,F-75475 PARIS 10,FRANCE. RI Chanson, Philippe/F-8511-2013 NR 0 TC 3 Z9 3 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 AUG PY 1993 VL 8 SU 1 BP S139 EP S139 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500091 ER PT J AU TANAKA, H QUARTO, R WILLIAMS, S BARNES, J LIANG, CT AF TANAKA, H QUARTO, R WILLIAMS, S BARNES, J LIANG, CT TI IN-VIVO AND IN-VITRO EFFECTS OF IGF-I ON FEMORAL GENE-EXPRESSION IN AGED RATS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1993 VL 8 SU 1 BP S155 EP S155 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500155 ER PT J AU TOBIN, JD FOX, KM CEJKU, ML ROY, TA EPSTEIN, RS PLATO, CC AF TOBIN, JD FOX, KM CEJKU, ML ROY, TA EPSTEIN, RS PLATO, CC TI BONE-DENSITY CHANGES IN NORMAL MEN - A 4-19 YEAR LONGITUDINAL-STUDY SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 UNIV MARYLAND,COLL PK,MD 20742. NIA,BALTIMORE,MD 21224. NR 0 TC 10 Z9 10 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 AUG PY 1993 VL 8 SU 1 BP S142 EP S142 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500103 ER PT J AU VANDERPLUIJM, G KERR, J LOWIK, C ROBEY, RG AF VANDERPLUIJM, G KERR, J LOWIK, C ROBEY, RG TI BETA-1 AND BETA-3 INTEGRIN SUBUNITS ARE INVOLVED IN ADHESION OF BREAST-CANCER CELLS TO EXTRACELLULAR BONE-MATRIX SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 LEIDEN UNIV HOSP,2333 AA LEIDEN,NETHERLANDS. NIDR,BRB,BETHESDA,MD 20892. NR 0 TC 11 Z9 11 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 AUG PY 1993 VL 8 SU 1 BP S136 EP S136 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500078 ER PT J AU WUCHERPFENNIG, AL LI, YP STETLERSTEVENSON, WG ROSENBERG, AE STASHENKO, P AF WUCHERPFENNIG, AL LI, YP STETLERSTEVENSON, WG ROSENBERG, AE STASHENKO, P TI EXPRESSION OF GELATINASE-B/92 KDA TYPE-IV COLLAGENASE IN HUMAN OSTEOCLASTS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 FORSYTH RES INST,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1993 VL 8 SU 1 BP S164 EP S164 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500189 ER PT J AU XU, XP BELLIDO, T RICE, N MANOLAGAS, SC AF XU, XP BELLIDO, T RICE, N MANOLAGAS, SC TI THE MOLECULAR-BASIS OF THE REGULATION OF THE TRANSCRIPTION FACTOR NF-KAPPA-B BY 1,25(OH)2D(3) IN LYMPHOCYTES - DEMONSTRATION OF INHIBITION AT THE MESSENGER-RNA LEVEL SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 RICHARD L ROUDEBUSH VET ADM MED CTR,ENDOCRINOL & METAB SECT,INDIANAPOLIS,IN 46202. INDIANA UNIV,DEPT MED,INDIANAPOLIS,IN 46204. NCI,BASIC RES PROGRAM,FREDERICK,MD 21701. NR 0 TC 0 Z9 0 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 AUG PY 1993 VL 8 SU 1 BP S126 EP S126 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500040 ER PT J AU YOUNG, MF IBARAKI, K KERR, JM LYU, MS KOZAK, CA AF YOUNG, MF IBARAKI, K KERR, JM LYU, MS KOZAK, CA TI MURINE BONE SIALOPROTEIN-CDNA CLONING MESSENGER-RNA EXPRESSION AND CHROMOSOME MAPPING SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDR,BETHESDA,MD 20892. NIAID,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 1993 VL 8 SU 1 BP S178 EP S178 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR205 UT WOS:A1993LR20500246 ER PT J AU LAKATTA, EG GUARNIERI, T AF LAKATTA, EG GUARNIERI, T TI SPONTANEOUS MYOCARDIAL CALCIUM OSCILLATIONS - ARE THEY LINKED TO VENTRICULAR-FIBRILLATION SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE CA2+ DEPENDENT CARDIAC ARRHYTHMIAS; SARCOPLASMIC RETICULUM; SPONTANEOUS CA2+ OSCILLATIONS; VENTRICULAR FIBRILLATION AB The physiological oscillation of cytosolic [Ca2+] that underlies each heart beat is generated by the sarcoplasmic reticulum (SR) in response to an actin potential (AP) and occurs relatively synchronously within and among cells. When the myocardial cell and SR Ca2+ loading become sufficiently high, the SR can also generate spontaneous, i.e., not triggered by sarcolemmal depolarization, Ca2+ oscillations (S-CaOs). The purpose of this review is to describe properties of S-CaOs in individual cells, myocardial tissue, and the intact heart, and to examine the evidence that may link S-CaOs to the initiation or maintenance of ventricular fibrillation (VF). The SR Ca2-release that generates S-CaOs occurs locally within cells and spreads within the cell via Ca2+ induced Ca2+ release. The localized increase in cytosolic [Ca2+] due to S-CaOs may equal that induced by an AP and causes oscillatory sarcolemmal depolarizations of cells in which it occurs. These oscillatory depolarizations are due to Ca2+ activation of the Na/Ca exchanger and of nonspecific cation channels. Asynchronous occurrence of diastolic S-CaOs among cells within the myocardium causes inhomogeneity of diastolic SR Ca2+ loading; this leads to inhomogeneity of the systolic cytosolic [Ca2+] transient levels in response to a subsequent AP, which leads to heterogeneity of AP repolarization, due to heterogeneous Ca2+ modulation of the Na/Ca exchanger, nonspecific cation channels, and of the L-type Ca2+ channel. In a tissue in which asynchronous S-CaOs am occurring in diastole, the subsequent AP temporarily synchronizes SR Ca2+ loading and release within and among cells. Varying extents of synchronized S-CaOs then begin to occur during the subsequent diastole. The partial synchronization of this diastolic S-CaOs cells within myocardial tissue produces aftercontractions and diastolic depolarizations. When S-CaOs are sufficiently synchronized, the resultant depolarizations summate and can be sufficient to trigger a spontaneous AP. S-CaOs occurrence within some cells during a long AP plateau also modulates the removal of voltage inactivation of L-type Ca2+ channels and increases the likelihood for ''early after depolarizations'' to occur in myocardial tissue. S-CaOs have an apparent modulatory role in the initiation of VF in the Ca2+ overload model and in the reflow period following ischemia. Likewise, in non-a priori Ca2+ overloaded hearts, S-CaOs modulate die threshold for VF induction (induced typically by alternating current) but may not be essential for VF induction. The role of S-CaOs in maintenance of VF in these VF models is less clear: to date there is no evidence that inhibition of S-CaOs can abolish VF once it has been established. The precise definition of the role of S-CaOs in the initiation and mechanisms of VF merits further study. RP LAKATTA, EG (reprint author), NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 0 TC 71 Z9 75 U1 0 U2 3 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD AUG PY 1993 VL 4 IS 4 BP 473 EP 489 DI 10.1111/j.1540-8167.1993.tb01285.x PG 17 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LR828 UT WOS:A1993LR82800009 PM 8269314 ER PT J AU DIODATI, JG QUYYUMI, AA KEEFER, LK AF DIODATI, JG QUYYUMI, AA KEEFER, LK TI COMPLEXES OF NITRIC-OXIDE WITH NUCLEOPHILES AS AGENTS FOR THE CONTROLLED BIOLOGICAL RELEASE OF NITRIC-OXIDE - HEMODYNAMIC-EFFECT IN THE RABBIT SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Article DE NITROVASODILATOR; RABBIT; NITRIC OXIDE; HEMODYNAMIC ID VASCULAR SMOOTH-MUSCLE; ENDOTHELIAL-CELLS; ORGANIC NITRATES; S-NITROSOTHIOLS; PHARMACOLOGY; RELAXATION; ACETYLCHOLINE; NITROPRUSSIDE; MECHANISM; TONE AB Nitric oxide (NO) and drugs that generate NO are potent vasodilators. We investigated the in vivo vasodilator potential of a unique group of compounds that release NO spontaneously in solution, the NO/nucleophile complexes. The hemodynamic effects of diethylamine/NO complex (DEA/NO) (half-life <3 min) and the spermine/NO complex (SPER/NO) (half-life >30 min) administered intravenously were compared with those of sodium nitroprusside in anesthetized New Zealand white rabbits. Arterial pressure and systemic vascular resistance decreased, but central venous pressure, pulmonary arterial pressure, heart rate, and thermodilution cardiac output did not change in association with any of the three drugs in the doses administered. The hemodynamic effects were dose dependent. As predicted from their rates of spontaneous NO release, DEA/NO is a short-acting vasodilator with a duration similar to that of sodium nitroprusside. whereas SPER/NO is a longer-acting agent with a significant hypotensive effect 30 min after bolus injection. DEA/NO was equipotent to sodium nitroprusside, causing significant reductions in blood pressure and systemic vascular resistance at the lowest dose tested (1.5 nmol/kg). The data indicate that the NO/nucleophile complexes have predictable vasorelaxant effects in vivo as well as in vitro and suggest that their amenability to facile structure-reactivity and structure-activity modification should allow the design of NO donor drugs for a variety of applications in cardiovascular pharmacology. C1 NCI,FREDERICK CANC RES & DEV CTR,CHEM SECT,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21701. NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 29 TC 46 Z9 46 U1 1 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0160-2446 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD AUG PY 1993 VL 22 IS 2 BP 287 EP 292 DI 10.1097/00005344-199308000-00018 PG 6 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA LP845 UT WOS:A1993LP84500018 PM 7692171 ER PT J AU FABIAN, JR MORRISON, DK DAAR, IO AF FABIAN, JR MORRISON, DK DAAR, IO TI REQUIREMENT FOR RAF AND MAP KINASE FUNCTION DURING THE MEIOTIC MATURATION OF XENOPUS-OOCYTES SO JOURNAL OF CELL BIOLOGY LA English DT Article ID NERVE GROWTH-FACTOR; MICROTUBULE-ASSOCIATED PROTEIN-2; SERINE THREONINE KINASES; PROTO-ONCOGENE PRODUCT; CELL-CYCLE CONTROL; STIMULATED PROTEIN; TYROSINE PHOSPHORYLATION; SIGNAL TRANSDUCTION; SWISS 3T3-CELLS; LAEVIS OOCYTES AB The role of Raf and MAPK (mitogen-activated protein kinase) during the maturation of Xenopus oocytes was investigated. Treatment of oocytes with progesterone resulted in a shift in the electrophoretic mobility of Raf at the onset of germinal vesicle breakdown (GVBD), which was coincident with the activation of MAPK. Expression of a kinase-defective mutant of the human Raf-1 protein (KD-RAF) inhibited progesterone-mediated MAPK activation. MAPK activation was also inhibited by KD-Raf in oocytes expressing signal transducers of the receptor tyrosine kinase (RTK) pathway, including an activated tyrosine kinase (Tpr-Met), a receptor tyrosine kinase (EGFr), and Ha-Ras(V12). KD-RAF completely inhibited GVBD induced by the RTK pathway. In contrast, KD-RAF did not inhibit GVBD and the progression to Meiosis II in progesterone-treated oocytes. Injection of Mos-specific antisense oligodeoxy-ribonucleotides inhibited MAPK activation in response to progesterone and Tpr-Met, but failed to inhibit these events in oocytes expressing an oncogenic deletion mutant of Raf-1 (DELTAN'Raf). Injection of antisense oligodeoxyribonucleotides to Mos also reduced the progesterone- and Tpr-Met-induced electrophoretic mobility shift of Xenopus Raf. These results demonstrate that RTKs and progesterone participate in distinct yet overlapping signaling pathways resulting in the activation of maturation or M-phase promoting factor (MPF). Maturation induced by the RTK pathway requires activation of Raf and MAPK, while progesterone-induced maturation does not. Furthermore, the activation of MAPK in oocytes appears to require the expression of Mos. C1 NCI,FREDERICK CANC RES & DEV CTR,LEUKOCYTE BIOL LAB,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. RP FABIAN, JR (reprint author), NCI,FREDERICK CANC RES & DEV CTR,MOLEC MECHANISMS CARCINOGENESIS LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702, USA. OI Daar, Ira/0000-0003-2657-526X FU PHS HHS [N01-C0-74101] NR 76 TC 130 Z9 130 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD AUG PY 1993 VL 122 IS 3 BP 645 EP 652 DI 10.1083/jcb.122.3.645 PG 8 WC Cell Biology SC Cell Biology GA LP642 UT WOS:A1993LP64200013 PM 8335690 ER PT J AU FLEMING, WH ALPERN, EJ UCHIDA, N IKUTA, K SPANGRUDE, GJ WEISSMAN, IL AF FLEMING, WH ALPERN, EJ UCHIDA, N IKUTA, K SPANGRUDE, GJ WEISSMAN, IL TI FUNCTIONAL-HETEROGENEITY IS ASSOCIATED WITH THE CELL-CYCLE STATUS OF MURINE HEMATOPOIETIC STEM-CELLS SO JOURNAL OF CELL BIOLOGY LA English DT Article ID BONE-MARROW; MOUSE; FLUORESCENCE; SEPARATION; ENRICHMENT; EXPRESSION; SUICIDE; SPLEEN; SYSTEM; GENE AB Hematopoietic stem cells (HSCs) are characterized by their ability to differentiate into all hematopoietic cell lineages while retaining their capacity for self renewal. One of the predictions of this model is the existence of a heterogeneous pool of HSCs, some members of which are destined to become lineage restricted progenitor cells while others function to renew the stem cell pool. To test whether HSCs are heterogeneous with respect to cell cycle status, we determined the fraction of phenotypically defined murine HSCs (Thy1.1lo Lin-/lo Sca-1+) that contain > 2n amount of DNA as measured by propidium iodide staining, Hoechst dye uptake and [H-3]thymidine labeling; that fraction is 18-22%. In contrast, in the developing fetal liver, 40% of HSCs are in the S/G2/M phases of the cell cycle. Those HSCs which exhibit a low level of staining with rhodamine 123 are almost exclusively in G0/G1 (97%) whereas only 70% of HSCs which stain brightly for rhodamine 123 are in G0/G1. The injection of 100 G0/G1 HSCs rescued 90% of lethally irradiated mice in contrast to 100 S/G2/M HSCs, which protected only 25% of lethally irradiated recipients. Enhanced long-term donor-derived multilineage reconstitution of the peripheral blood was observed in recipients of 100 G0/G1 HSCs compared to recipients of 100 S/G2/M cells. These data indicate that a significant proportion of HSCs are actively proliferating during steady state hematopoiesis and that this subpopulation of cells exhibits reduced stem cell activity. C1 NIAID,PERSISTENT VIRAL DIS LAB,ROCKY MT LABS,HAMILTON,MT 59840. STANFORD UNIV,DEPT MED,DIV ONCOL,STANFORD,CA 94305. STANFORD UNIV,DEPT PATHOL,DIV ONCOL,STANFORD,CA 94305. STANFORD UNIV,DEPT DEV BIOL,DIV ONCOL,STANFORD,CA 94305. FU NCI NIH HHS [CA-42551] NR 26 TC 203 Z9 206 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD AUG PY 1993 VL 122 IS 4 BP 897 EP 902 DI 10.1083/jcb.122.4.897 PG 6 WC Cell Biology SC Cell Biology GA LR629 UT WOS:A1993LR62900013 PM 8349737 ER PT J AU LOVERIDGE, N FARQUHARSON, C HESKETH, JE JAKOWLEW, SB WHITEHEAD, CC THORP, BH AF LOVERIDGE, N FARQUHARSON, C HESKETH, JE JAKOWLEW, SB WHITEHEAD, CC THORP, BH TI THE CONTROL OF CHONDROCYTE DIFFERENTIATION DURING ENDOCHONDRAL BONE-GROWTH IN-VIVO - CHANGES IN TGF-BETA AND THE PROTOONCOGENE C-MYC SO JOURNAL OF CELL SCIENCE LA English DT Article DE TRANSFORMING GROWTH FACTOR-BETA; PROTOONCOGENE C-MYC; GROWTH PLATE; CHONDROCYTE DIFFERENTIATION; ENDOCHONDRAL OSSIFICATION; CHICKEN DYSCHONDROPLASIA; OSTEOCLASTS; CARTILAGE ID AVIAN TIBIAL DYSCHONDROPLASIA; PLATE CHONDROCYTES; MESSENGER-RNA; CELL-DIFFERENTIATION; ALKALINE-PHOSPHATASE; MATRIX VESICLES; X COLLAGEN; EXPRESSION; CARTILAGE; GENE AB The expression of transforming growth factor-beta and the c-myc proto-oncogene was studied in situ in the chondrocytes of the tibial growth plate of normal chicks and those with avian tibial dyschondroplasia in which the chondrocytes are developmentally arrested in the transitional phase between proliferation and differentiation. This results in an accumulation of unmineralised and avascular cartilage. Dyschondroplastic chicks showed reduced c-myc expression in the transitional chondrocytes but unaltered levels in the proliferating chondrocytes. Transforming growth factor-beta expression was reduced in the transitional chondrocytes of dyschondroplastic chicks. In areas where the lesion was being repaired there was evidence of increased expression of both c-myc protein and transforming growth factor-beta. Addition of 1,25-dihydroxyvitamin D to the diet, which is known to reduce the incidence of dyschondroplasia, resulted in an increase in c-myc production. These results suggest that both transforming growth factor-beta and the proto-oncogene c-myc may be important elements of the cascade of events that lead to chondrocyte differentiation, hypertrophy and mineralisation. C1 AFRC, INST ANIM PHYSIOL & GENET, ROSLIN, MIDLOTHIAN, SCOTLAND. NIH, CHEMOPREVENT LAB, BETHESDA, MD 20892 USA. RP LOVERIDGE, N (reprint author), ROWETT RES INST, BONE GROWTH & METAB UNIT, GREENBURN RD, BUCKSBURN AB2 9SB, ABERDEEN, SCOTLAND. NR 61 TC 66 Z9 67 U1 1 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD AUG PY 1993 VL 105 BP 949 EP 956 PN 4 PG 8 WC Cell Biology SC Cell Biology GA LV687 UT WOS:A1993LV68700009 PM 8227216 ER PT J AU SCHNAPER, HW GRANT, DS STETLERSTEVENSON, WG FRIDMAN, R DORAZI, G MURPHY, AN BIRD, RE HOYTHYA, M FUERST, TR FRENCH, DL QUIGLEY, JP KLEINMAN, HK AF SCHNAPER, HW GRANT, DS STETLERSTEVENSON, WG FRIDMAN, R DORAZI, G MURPHY, AN BIRD, RE HOYTHYA, M FUERST, TR FRENCH, DL QUIGLEY, JP KLEINMAN, HK TI TYPE-IV COLLAGENASE(S) AND TIMPS MODULATE ENDOTHELIAL-CELL MORPHOGENESIS IN-VITRO SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID EXTRACELLULAR-MATRIX COMPONENTS; BASEMENT-MEMBRANE COLLAGEN; CAPILLARY-LIKE STRUCTURES; TISSUE INHIBITOR; TUMOR ANGIOGENESIS; INTERSTITIAL COLLAGENASE; PLASMINOGEN-ACTIVATOR; PROTEOLYTIC ACTIVITY; EXPRESSION; GROWTH AB It has been proposed that proteases are important in endothelial cell behavior. We examined the contribution of the gelatinase/type IV collagenase system in an in vitro model of endothelial differentiation. Human umbilical vein endothelial cells rapidly align and form networks of tubes when cultured on a basement membrane preparation, Matrigel. Zymograms of culture supernates demonstrate a 72-kD and a 92-kD gelatinase activity; the cells produce most of the 72-kD gelatinase, whereas the 92-kD activity is derived entirely from the Matrigel. Addition of antibodies against type IV gelatinase/collagenase decreases the area of the tube network. Both tissue inhibitors of metalloproteinases, TIMP-1 and TIMP-2, similarly decrease tube formation when added to cultures. Conversely, exogenous recombinant 72-kD gelatinase increases tube-forming activity. The effects of the anti-gelatinase antibodies and the TIMPs are not additive. Inhibition by either antibodies or TIMPs is greatest when they are added at culture initiation, suggesting that the protease activity is important in the early steps of morphogenesis. However, culture of the cells on Matrigel does not increase early expression of mRNA for the 72-kD gelatinase. Expression of message for the enzyme actually decreases during the course of the assay, while transcription of mRNAs for TIMPs increases, further supporting the concept that collagenases facilitate an early event in tube formation. These data demonstrate that gelatinase/type IV collagenase activity is important in endothelial cell morphogenesis on Matrigel, and suggest a role for collagenases in formation of new capillaries in vivo. (C) 1993 Wiley-Liss, Inc. C1 NCI, PATHOL LAB, BETHESDA, MD 20892 USA. CHILDRENS HOSP, NATL MED CTR, DEPT NEPHROL, WASHINGTON, DC 20010 USA. MOLEC ONCOL INC, GAITHERSBURG, MD 20878 USA. SUNY, DEPT PATHOL, STONY BROOK, NY 11794 USA. RP SCHNAPER, HW (reprint author), NIDR, DEV BIOL LAB, BETHESDA, MD 20892 USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 FU NIDDK NIH HHS [NRSA DK08712] NR 53 TC 257 Z9 259 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD AUG PY 1993 VL 156 IS 2 BP 235 EP 246 DI 10.1002/jcp.1041560204 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA LP822 UT WOS:A1993LP82200003 PM 8344982 ER PT J AU SCHNEIDER, AB RON, E LUBIN, J STOVALL, M GIERLOWSKI, TC AF SCHNEIDER, AB RON, E LUBIN, J STOVALL, M GIERLOWSKI, TC TI DOSE-RESPONSE RELATIONSHIPS FOR RADIATION-INDUCED THYROID-CANCER AND THYROID-NODULES - EVIDENCE FOR THE PROLONGED EFFECTS OF RADIATION ON THE THYROID SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CHILDHOOD IRRADIATION; TUMORS; HEAD AB The risk of developing thyroid cancer and other thyroid neoplasms after radiation exposure is well known, but specific modifiers of the dose-response relationship are not. We have identified 4296 subjects who received treatment before their sixteenth birthday with orthovoltage radiation for benign conditions in the head and neck area. Individual thyroid dose estimates were calculated for 3843 subjects. Of the 2634 subjects who have been found, 1043 have developed thyroid nodules of all types, and 309 have developed thyroid cancer. The radiation dose-response relationship was consistent with a linear excess relative risk model for thyroid cancer and thyroid nodules within the range of observed doses. Women developed thyroid cancer and thyroid nodules at a higher rate, but the slopes of the dose-response curves were the same for men and women. Age at radiation exposure was a significant factor of the risk, with a lower age at exposure associated with a higher risk. To determine the effect of the wide publicity and our screening program, which began in 1974, we compared the dose-response relationship for cases diagnosed before and after 1974. The overall rates increased dramatically after 1974, but the estimates of the slopes of the dose-response curves were not statistically different. The slope of the dose-response curve for thyroid neoplasms appears to have reached a maximum 25-29 yr after radiation exposure, but the dose response continued to be elevated at the end of follow-up. These data are consistent with the tumorigenic effects of radiation lasting at least 40 yr. C1 UNIV TEXAS, M D ANDERSON CANC CTR, DEPT RADIAT PHYS, HOUSTON, TX 77030 USA. NCI, BIOSTAT BRANCH, BETHESDA, MD 20892 USA. NCI, RADIAT EPIDEMIOL BRANCH, BETHESDA, MD 20892 USA. RP SCHNEIDER, AB (reprint author), UNIV ILLINOIS, MICHAEL REESE HOSP, DIV ENDOCRINOL & METAB, 216-RC, 2929 S ELLIS AVE, CHICAGO, IL 60616 USA. FU NCI NIH HHS [CA-21518, N01-CP-05609, N01-CP-85604] NR 22 TC 165 Z9 174 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 1993 VL 77 IS 2 BP 362 EP 369 DI 10.1210/jc.77.2.362 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR719 UT WOS:A1993LR71900015 PM 8345040 ER PT J AU YANOVSKI, JA CUTLER, GB DOPPMAN, JL MILLER, DL CHROUSOS, GP OLDFIELD, EH NIEMAN, LK AF YANOVSKI, JA CUTLER, GB DOPPMAN, JL MILLER, DL CHROUSOS, GP OLDFIELD, EH NIEMAN, LK TI THE LIMITED ABILITY OF INFERIOR PETROSAL SINUS SAMPLING WITH CORTICOTROPIN-RELEASING HORMONE TO DISTINGUISH CUSHINGS-DISEASE FROM PSEUDO-CUSHING STATES OR NORMAL PHYSIOLOGY SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID DIFFERENTIAL-DIAGNOSIS; STIMULATION TEST; ACTH; BLOOD; ADRENOCORTICOTROPIN; SECRETION; MICROADENOMAS AB To determine whether petrosal sinus sampling is useful to distinguish patients with mild or intermittent Cushing's disease from normal subjects and individuals with pseudo-Cushing states, we performed bilateral inferior petrosal sinus sampling for ACTH before and after the administration of CRH in 7 eucortisolemic volunteers, 8 hypercortisolemic patients with pseudo-Cushing states, and 40 patients with ACTH-dependent Cushing's disease whose urinary free cortisol excretion was within the range found in patients with pseudo-Cushing states (<1000 nmol/day; <360 mug/day). The ACTH level, the ratio of the inferior petrosal sinus ACTH to the peripheral venous ACTH concentration (the IPS:P ratio), and the greater ratio of right to left or left to right petrosal sinuses (the R:L ratio) were compared in patients with and without Cushing's disease. Maximal petrosal ACTH values were significantly elevated in patients with Cushing's disease compared to patients with pseudo-Cushing states before CRH administration (P < 0.001), but not after CRH. Maximal petrosal plasma ACTH values after the administration of CRH as high as 808 pmol/L (3670 pg/mL) and 469 pmol/L (2130 pg/mL) were found in patients with pseudo-Cushing states and in normal volunteers, respectively, whereas maximal petrosal ACTH levels as low as 10 pmol/L (46 pg/mL) were observed in patients with surgically proven Cushing's disease. Maximal and minimal IPS:P ratios were significantly greater in patients with Cushing's disease than in subjects without Cushing's disease before, but not after, CRH treatment. R:L ratios did not differ among groups either before or after CRH. All of the subjects without Cushing's disease showed large R:L gradients, consistent with the notion of one dominant petrosal sinus containing a greater percentage of pituitary effluent. The ACTH concentrations, IPS:P ratios, and R:L ratios exhibited great overlap between those with and without Cushing's disease, which resulted in a diagnostic accuracy of 81% at best for the diagnosis of Cushing's disease. We conclude that petrosal sinus sampling is of limited usefulness in distinguishing either normal individuals or patients with pseudo-Cushing states from those with mild Cushing's disease. This limited usefulness must be recognized when interpreting the results of petrosal sinus sampling in patients with mild or intermittent hypercortisolism who may have a pseudo-Cushing state. Because of these limitations, petrosal sinus sampling should be reserved for patients with clear clinical and biochemical evidence of Cushing's syndrome. C1 NINCDS, SURG NEUROL BRANCH, BETHESDA, MD 20892 USA. NINCDS, DEPT DIAGNOST RADIOL, CTR CLIN, BETHESDA, MD 20892 USA. NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. OI Yanovski, Jack/0000-0001-8542-1637 NR 33 TC 57 Z9 60 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 1993 VL 77 IS 2 BP 503 EP 509 DI 10.1210/jc.77.2.503 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR719 UT WOS:A1993LR71900040 PM 8393887 ER PT J AU YANOVSKI, JA YANOVSKI, SZ GOLD, PW CHROUSOS, GP AF YANOVSKI, JA YANOVSKI, SZ GOLD, PW CHROUSOS, GP TI DIFFERENCES IN THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS OF BLACK-AND-WHITE WOMEN SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; DEXAMETHASONE SUPPRESSION TEST; RACIAL-DIFFERENCES; FAT-CELLS; OBESITY; HORMONE; CORTISOL; ADRENOCORTICOTROPIN; GLUCOCORTICOIDS; DIFFERENTIATION AB Alterations in the activity of the hypothalamic-pituitary-adrenal (HPA) axis have been associated with obesity in humans and animals. To explore possible mechanisms responsible for the higher prevalence of obesity and its associated comorbid conditions in the black population, we studied the HPA axis of 18 black and 30 white weight- and age-matched nonobese and obese women. Waist to hip ratio, 24-h urinary free cortisol excretion, plasma cortisol responses to dexamethasone, and plasma ACTH and cortisol responses to lug/kg ovine CRH were determined. There were no racial differences in waist to hip ratio, 24-h urinary free cortisol excretion, dexamethasone suppressibility of plasma cortisol, baseline plasma cortisol and ACTH concentrations, or plasma cortisol response to CRH. However, CRH-stimulated plasma ACTH concentrations, measured in an extraction polyclonal RIA, were significantly greater in blacks than in whites at all time points, beginning 5 min after the administration of CRH [area under the curve (AUC), 2463 +/- 288 pmol/L . min in blacks vs. 1185 +/- 78 in whites; P < 0.0011. These differences persisted when ACTH was measured by a 2-site direct immunoradiometric assay measuring the intact ACTH-(1-39) molecule (AUC, 1292 +/- 177 pmol/L . min in blacks vs. 504 +/- 95 in whites; P < 0.002). There was no significant correlation between body mass index and either cortisol or ACTH AUCs for either race, with blacks showing persistently elevated AUC for ACTH compared to whites, regardless of weight. We conclude that there are differences in the HPA axis of black and white women. How these differences may relate to the increased prevalence of obesity in the black population remains to be determined. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NIMH, CLIN NEUROENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NATL INST DIABET & DIGEST & KIDNEY DIS, DIV DIGEST DIS & NUTR, BETHESDA, MD 20892 USA. OI Yanovski, Jack/0000-0001-8542-1637 NR 44 TC 26 Z9 26 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 1993 VL 77 IS 2 BP 536 EP 541 DI 10.1210/jc.77.2.536 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LR719 UT WOS:A1993LR71900045 PM 8393890 ER PT J AU CROZIER, R BERNSTEIN, GS AF CROZIER, R BERNSTEIN, GS TI HISTORICAL BACKGROUND AND OBJECTIVES OF STUDY SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article ID PROSTATE-CANCER; VASECTOMY; RISK; MEN C1 UNIV SO CALIF,LOS ANGELES,CA 90089. RP CROZIER, R (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD AUG PY 1993 VL 46 IS 8 BP 697 EP 706 DI 10.1016/0895-4356(93)90178-4 PG 10 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA LP814 UT WOS:A1993LP81400002 ER PT J AU MCGREGOR, DD BENJAMIN, RB BERENDES, HW BERNSTEIN, GS COULSON, AH CROZIER, R EMSLANDER, RF QUIROGA, J SCHMIDT, S SCHUMAN, LM SULLIVAN, T AF MCGREGOR, DD BENJAMIN, RB BERENDES, HW BERNSTEIN, GS COULSON, AH CROZIER, R EMSLANDER, RF QUIROGA, J SCHMIDT, S SCHUMAN, LM SULLIVAN, T TI MEDICAL END-POINTS SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article C1 MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. UNIV CALIF LOS ANGELES,SCH PUBL HLTH,DEPT EPIDEMIOL,LOS ANGELES,CA 90024. UNIV TEXAS,DALLAS,TX 75230. UNIV MINNESOTA,SCH PUBL HLTH,MINNEAPOLIS,MN 55455. NICHHD,BETHESDA,MD 20892. UNIV SO CALIF,LOS ANGELES,CA 90089. RP MCGREGOR, DD (reprint author), CORNELL UNIV,ITHACA,NY 14853, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD AUG PY 1993 VL 46 IS 8 BP 753 EP 768 DI 10.1016/0895-4356(93)90184-3 PG 16 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA LP814 UT WOS:A1993LP81400008 ER PT J AU COULSON, AH BERENDES, HW MCGREGOR, DD NAKAMURA, RM AF COULSON, AH BERENDES, HW MCGREGOR, DD NAKAMURA, RM TI RISK-FACTORS SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article C1 UNIV SO CALIF,LOS ANGELES,CA 90089. NICHHD,BETHESDA,MD 20892. CORNELL UNIV,ITHACA,NY 14853. RP COULSON, AH (reprint author), UNIV CALIF LOS ANGELES,SCH PUBL HLTH,DEPT ANGEW MATH,LOS ANGELES,CA 90024, USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD AUG PY 1993 VL 46 IS 8 BP 791 EP 795 DI 10.1016/0895-4356(93)90186-5 PG 5 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA LP814 UT WOS:A1993LP81400010 ER PT J AU COULSON, AH CROZIER, R MASSEY, FJ OFALLON, WM SCHUMAN, LM SPIVEY, GH AF COULSON, AH CROZIER, R MASSEY, FJ OFALLON, WM SCHUMAN, LM SPIVEY, GH TI RESULTS SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article ID PROSTATE-CANCER; VASECTOMY; RISK C1 UNIV MINNESOTA,SCH PUBL HLTH,MINNEAPOLIS,MN 55455. MAYO CLIN & MAYO FDN,DEPT HLTH SCI RES,STAT SECT,ROCHESTER,MN 55905. UNIV SO CALIF,LOS ANGELES,CA 90089. NICHHD,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,SCH PUBL HLTH,DEPT BIOSTAT,LOS ANGELES,CA 90024. RP COULSON, AH (reprint author), UNIV CALIF LOS ANGELES,SCH PUBL HLTH,DEPT EPIDEMIOL,LOS ANGELES,CA 90024, USA. NR 10 TC 5 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD AUG PY 1993 VL 46 IS 8 BP 857 EP 920 DI 10.1016/0895-4356(93)90192-4 PG 64 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA LP814 UT WOS:A1993LP81400016 ER PT J AU KOVACS, JA VASUDEVACHARI, MB EASTER, M DAVEY, RT FALLOON, J POLIS, MA METCALF, JA SALZMAN, N BASELER, M SMITH, GE VOLVOVITZ, F MASUR, H LANE, HC AF KOVACS, JA VASUDEVACHARI, MB EASTER, M DAVEY, RT FALLOON, J POLIS, MA METCALF, JA SALZMAN, N BASELER, M SMITH, GE VOLVOVITZ, F MASUR, H LANE, HC TI INDUCTION OF HUMORAL AND CELL-MEDIATED ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) RESPONSES IN HIV SERONEGATIVE VOLUNTEERS BY IMMUNIZATION WITH RECOMBINANT GP160 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE AIDS; RETROVIRUS; SAFETY; IMMUNOGENICITY; VACCINE ID LYMPHOCYTE PROLIFERATIVE RESPONSES; PLACEBO-CONTROLLED TRIAL; AIDS-RELATED COMPLEX; CYTOLYTIC T-CELLS; NEUTRALIZING ANTIBODIES; ENVELOPE GLYCOPROTEIN; SEROPOSITIVE INDIVIDUALS; VACCINE PROTECTION; RESTRICTED NEUTRALIZATION; CANDIDATE VACCINE AB Development of an effective vaccine for prevention of infection with HIV would provide an important mechanism for controlling the AIDS epidemic. In the current study, the first clinical trial of a candidate HIV-1 vaccine initiated in the United States, the safety and immunogenicity of escalating doses (10-1,280 mug) of recombinant gp160 (rgp160), were evaluated in 138 HIV-negative volunteers. Maximal antibody responses, as evaluated by ELISA, were seen after immunization with three doses of 1,280 mug rgp160. Responses to some specific epitopes of HIV gp160, including the second conserved domain and the CD4 binding site, were seen more frequently than after natural infection. Neutralizing antibodies to the homologous HIV strain, but not heterologous strains, were induced by this regimen. Blastogenic responses to rgp160 were seen in most volunteers receiving at least two doses of greater-than-or-equal-to 20 mug. These envelope-specific T cell responses were also seen against heterologous strains of HIV. No major adverse reactions were seen after immunization. Thus, rgp160 is a safe and immunogenic candidate HIV vaccine; further studies are needed to determine if it will provide any clinical benefit in preventing HIV infection. C1 GEORGETOWN UNIV,DEPT MICROBIOL,MOLEC RETROVIROL LAB,WASHINGTON,DC 20007. NIAID,IMMUNOREGULAT LAB,CLIN & MOLEC RETROVIROL SECT,BETHESDA,MD 20892. PROGRAM RESOURCES INC,FREDERICK,MD 21702. MICROGENESYS INC,MERIDEN,CT 06450. RP KOVACS, JA (reprint author), NIH,CTR CLIN,DEPT CRIT CARE MED,BLDG 10,ROOM 7D43,BETHESDA,MD 20892, USA. OI Polis, Michael/0000-0002-9151-2268 FU NCI NIH HHS [N01-CO-74102] NR 70 TC 36 Z9 36 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 1993 VL 92 IS 2 BP 919 EP 928 DI 10.1172/JCI116667 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LT169 UT WOS:A1993LT16900050 PM 7688766 ER PT J AU MASTORAKOS, G WEBSTER, EL FRIEDMAN, TC CHROUSOS, GP AF MASTORAKOS, G WEBSTER, EL FRIEDMAN, TC CHROUSOS, GP TI IMMUNOREACTIVE CORTICOTROPIN-RELEASING HORMONE AND ITS BINDING-SITES IN THE RAT OVARY SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE OVARY; INFLAMMATION; CORTICOTROPIN-RELEASING HORMONE; FOLLICLE; CORPUS-LUTEUM ID CYTOKINE-MEDIATED REGULATION; SYMPATHETIC NERVOUS-SYSTEM; FACTOR RECEPTORS; DIVALENT-CATIONS; BETA-ENDORPHIN; LEYDIG-CELLS; SPINAL-CORD; FACTOR CRF; SECRETION; LOCALIZATION AB Corticotropin-releasing hormone (CRH), the principal neuropeptide regulator of pituitary ACTH secretion, is also produced at peripheral inflammatory sites, where it acts as a proinflammatory cytokine, and by the Leydig cell of the testis, where it exerts autocrine inhibition of testosterone biosynthesis. Because key ovarian functions, such as ovulation and luteolysis, represent aseptic inflammatory responses, and because the theca cell is the functional equivalent of the Leydig cell, we explored the CRH presence in the ovary, first, by specific CRH immunohistochemistry of adult cycling female Sprague-Dawley rat ovaries. We detected cytoplasmic immunoreactive CRH (IrCRH) in theca and stromal cells and in cells within the corpora lutea, at all phases of the estrous cycle. Using a specific radioimmunoassay, we measured IrCRH in extracts of rat ovaries (0.042-0.126 pmol/g wet tissue). The mobility of the ovarian IrCRH molecule was similar to that of rat/human CRH by reverse phase HPLC. To investigate the CRH action in the ovary, we identified, characterized, and localized CRH receptors in the rat ovary. Binding was linear with increasing tissue concentration, saturable, and of high affinity. Scatchard analysis of I-125-Tyr-ovine CRH competitive displacement curves indicated a high affinity binding site with a K(d) of almost-equal-to 6 nM and a B(max) value of almost-equal-to 61 f M/mg protein. Autoradiographic studies revealed CRH receptors primarily in ovarian theca and stroma. We conclude that IrCRH and CRH receptors are present in rat ovaries, suggesting that this neuropeptide may play a regulatory role in this gonad, perhaps through its proinflammatory properties and/or by participating in the auto/paracrine regulation of steroid biosynthesis. Functional studies are necessary to define the role(s) of CRH in the ovary. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD 20892. NR 46 TC 94 Z9 94 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 1993 VL 92 IS 2 BP 961 EP 968 DI 10.1172/JCI116672 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LT169 UT WOS:A1993LT16900055 PM 8394389 ER PT J AU PANOS, RJ RUBIN, JS AARONSON, SA MASON, RJ AF PANOS, RJ RUBIN, JS AARONSON, SA MASON, RJ TI KERATINOCYTE GROWTH-FACTOR AND HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR ARE HEPARIN-BINDING GROWTH-FACTORS FOR ALVEOLAR TYPE-II CELLS IN FIBROBLAST-CONDITIONED MEDIUM SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID STIMULATE DNA-SYNTHESIS; FETAL-RAT LUNG; EPITHELIAL-CELLS; FACTOR RECEPTORS; PARTIAL PNEUMONECTOMY; PULMONARY FIBROSIS; MOLECULAR-CLONING; MET PROTOONCOGENE; HEPATOPOIETIN-A; PRIMARY CULTURE AB Epithelial-mesenchymal interactions mediate aspects of normal lung growth and development and are important in the restoration of normal alveolar architecture after lung injury. To determine if fibroblasts are a source of soluble growth factors for alveolar type II cells, we investigated the effect of fibroblast-conditioned medium (CM) on alveolar type II cell DNA synthesis. Serum-free CM from confluent adult human lung fibroblasts was concentrated fivefold by lyophilization. Type II cells were isolated from adult rats by elastase dissociation and incubated with [H-3]thymidine and varying dilutions of concentrated CM and serum from day 1 to 3 of culture. Stimulation of type II cell DNA synthesis by fibroblast-CM was maximal after 48 h of conditioning and required the presence of serum. The activity of the CM was eliminated by boiling and by treatment with trypsin, pepsin, or dithiothreitol and was additive with saturating concentrations of acidic fibroblast growth factor, epidermal growth factor, and insulin. The growth factor activity bound to heparin-Sepharose and was eluted with 0.6 and 1.0 M NaCl. Neutralizing antibody studies demonstrated that the primary mitogens isolated in the 0.6 and 1.0 M NaCl fractions were keratinocyte growth factor (KGF, fibroblast growth factor 7) and hepatocyte growth factor/scatter factor (HGF/SF), respectively. HGF/SF was demonstrated in the crude CM and KGF was detected in the 0.6 M NaCl eluent by immunoblotting. Northern blot analysis confirmed that the lung fibroblasts expressed both KGF and HGF/SF transcripts. Human recombinant KGF and HGF/SF induced a concentration- and serum-dependent increase in rat alveolar type II cell DNA synthesis. We conclude that adult human lung fibroblasts produce at least two soluble heparin-binding growth factors, KGF and HGF/SF, which promote DNA synthesis and proliferation of rat alveolar type II cells in primary culture. KGF and HGF/SF may be important stimuli for alveolar type II cell proliferation during lung growth and after lung injury. C1 NCI,CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. UNIV COLORADO,HLTH SCI CTR,DIV PULM,DENVER,CO 80206. RP PANOS, RJ (reprint author), NORTHWESTERN UNIV,SCH MED,DEPT MED,DIV PULM,WESLEY PAVIL,ROOM 456,250 E SUPER ST,CHICAGO,IL 60611, USA. FU NHLBI NIH HHS [HL-27353, HL-29891] NR 74 TC 249 Z9 254 U1 0 U2 4 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 AUG PY 1993 VL 92 IS 2 BP 969 EP 977 DI 10.1172/JCI116673 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LT169 UT WOS:A1993LT16900056 PM 7688769 ER PT J AU RADER, DJ SCHAFER, J LOHSE, P VERGES, B KINDT, M ZECH, LA STEINMETZ, A BREWER, HB AF RADER, DJ SCHAFER, J LOHSE, P VERGES, B KINDT, M ZECH, LA STEINMETZ, A BREWER, HB TI RAPID IN-VIVO TRANSPORT AND CATABOLISM OF HUMAN APOLIPOPROTEIN A-VI-1 AND SLOWER CATABOLISM OF THE APOA-IV-2 ISOPROTEIN SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE HIGH DENSITY LIPOPROTEINS; CHOLESTEROL; ATHEROSCLEROSIS; KINETICS; TRIGLYCERIDES ID HIGH-DENSITY-LIPOPROTEIN; A-IV POLYMORPHISM; ESTER TRANSFER PROTEIN; HUMAN-PLASMA; CHOLESTEROL ACYLTRANSFERASE; MONOCLONAL-ANTIBODIES; LYMPH; METABOLISM; BINDING; GENE AB Apolipoprotein (apo) A-IV is a polymorphic, intestinally derived apolipoprotein that is genetically linked to and similar in structure to apoA-I, the major apolipoprotein in high density lipoproteins (HDL). ApoA-IV plays a potentially important role in lipoprotein metabolism and reverse cholesterol transport, but its in vivo metabolism is poorly understood. In order to gain insight into factors modulating apoA-IV metabolism in humans, the in vivo kinetics of the two major human apoA-IV isoproteins apoA-IV-1 and apoA-IV-2 were investigated in normolipidemic human subjects. I-131-apoA-IV-1 and I-125-apoA-IV-2 were reassociated with autologous plasma and injected into study subjects. Analysis of the kinetic data revealed a rapid mean fractional catabolic rate (FCR) for apoA-IV-1 of 2.42 +/- 0.11 d-1. The mean production, or transport, rate of apoA-IV-1 was 16.3 +/- 1.4 mg/kg per d. Plasma apoA-IV concentrations were highly correlated with apoA-IV production rate (r = 0.84, P < 0.001) and not correlated with apoA-IV fractional catabolic rate (r = 0.25, P = NS). The mean FCR of apoA-IV-2 was 2.21 +/- 0.10 d-1. In the ten subjects in whom I-131-apoA-IV-1 and I-125-apoA-IV-2 were simultaneously injected, the FCR of apoA-IV-2 was significantly slower by paired t test (P = 0.003). The FCR of apoA-IV-2 in an apoA-IV-2/2 homozygote was only 1.49 d-1, substantially slower than in all other subjects. We conclude that: (a) apoA-IV is a rapidly catabolized apolipoprotein in humans, with a fractional catabolic rate more than 10 times greater than that of apoA-1; (b) apoA-IV has a high absolute transport rate similar to that of apoA-1; (c) plasma levels of apoA-IV are primarily determined by apoA-IV production rate in normolipidemic subjects; and (d) the fractional catabolic rate of the common variant apoA-IV-2 is slower than that of the wild-type apoA-IV-1. C1 PHILLIPPS UNIV MARBURG,CTR INTERNAL MED,DIV ENDOCRINOL & METAB,MARBURG,GERMANY. RP RADER, DJ (reprint author), NHLBI,MOLEC DIS BRANCH,BLDG 10,ROOM 7N117,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 62 TC 38 Z9 40 U1 1 U2 4 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 AUG PY 1993 VL 92 IS 2 BP 1009 EP 1017 DI 10.1172/JCI116606 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LT169 UT WOS:A1993LT16900061 PM 8349786 ER PT J AU PARMER, RJ XI, XP WU, HJ HELMAN, LJ PETZ, LN AF PARMER, RJ XI, XP WU, HJ HELMAN, LJ PETZ, LN TI SECRETORY PROTEIN TRAFFIC - CHROMOGRANIN-A CONTAINS A DOMINANT TARGETING SIGNAL FOR THE REGULATED PATHWAY SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE CATECHOLAMINE; CHROMAFFIN CELLS; CHROMOGRANIN A; PC-12; PHEOCHROMOCYTOMA; REGULATED SECRETION ID ADRENAL CHROMAFFIN GRANULES; HUMAN GROWTH-HORMONE; TRANSFECTED PC12 CELLS; TRANS-GOLGI NETWORK; V-SIS GENE; SECRETOGRANIN-I; INTRACELLULAR-TRANSPORT; PHEOCHROMOCYTOMA CELLS; FIREFLY LUCIFERASE; ENDOCRINE TISSUES AB Secretory proteins are targeted into either constitutive (secreted upon synthesis) or regulated (stored in vesicles and released in response to a secretagogue) pathways. To investigate mechanisms of protein targeting into catecholamine storage vesicles (CSV), we stably expressed human chromogranin A (CgA), the major soluble protein in human CSV, in the rat pheochromocytoma PC-12 cell line. Chromaffin cell secretagogues (0.1 mM nicotinic cholinergic agonist, 55 mM K+, or 2 mM Ba++) caused cosecretion of human CgA and catecholamines from human CgA-expressing cells. Sucrose gradients colocalized human CgA and catecholamines to subcellular particles of the same buoyant density. Chimeric proteins, in which human CgA (either full-length 1457 amino acids] or truncated [amino-terminal 226 amino acids]) was fused in-frame to the ordinarily nonsecreted protein chloramphenicol acetyltransferase (CAT), were expressed transiently in PC-12 cells. Both constructs directed CAT activity into regulated secretory vesicles, as judged by secretagogue-stimulated release. These data demonstrate that human CgA expressed in PC-12 cells is targeted to regulated secretory vesicles. In addition, human CgA can divert an ordinarily non-secreted protein into the regulated secretory pathway, consistent with the operation of a dominant targeting signal for the regulated pathway within the peptide sequence of CgA. C1 VET AFFARIS MED CTR,SAN DIEGO,CA 92161. NCI,BETHESDA,MD 20892. RP PARMER, RJ (reprint author), UNIV CALIF SAN DIEGO,DEPT MED,3350 LA JOLLA DR,SAN DIEGO,CA 92161, USA. FU NHLBI NIH HHS [HL-50174] NR 88 TC 56 Z9 56 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 AUG PY 1993 VL 92 IS 2 BP 1042 EP 1054 DI 10.1172/JCI116609 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LT169 UT WOS:A1993LT16900064 PM 8394383 ER PT J AU COOMBS, RW HENRARD, DR MEHAFFEY, WF GIBSON, J EGGERT, E QUINN, TC PHILLIPS, J AF COOMBS, RW HENRARD, DR MEHAFFEY, WF GIBSON, J EGGERT, E QUINN, TC PHILLIPS, J TI CELL-FREE PLASMA HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TITER ASSESSED BY CULTURE AND IMMUNOCAPTURE-REVERSE TRANSCRIPTION-POLYMERASE CHAIN-REACTION SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID HIV INFECTION; VIREMIA; DISEASE; STAGE; RNA; REPLICATION; ASSAY; DNA AB The relationship between plasma human immunodeficiency virus type 1 (HIV-1) infectious titer, determined by quantitative fivefold end-point dilution culture, and the detection of genomic HIV-1 RNA by immunocapture-cDNA-polymerase chain reaction was determined. The optimal plasma specimen collection and storage conditions for the use of such virologic markers for clinical trials were also determined. The variabilities in the measurement of infectious HIV(LAI) titer associated with intra- and interdonor peripheral blood mononuclear cells were 1.2 and 0.86 log10 50% tissue culture infective doses (TCID50)/ml (95% confidence interval range), respectively. Plasma HIV-1 titers did not change significantly after storing whole blood for 6 h either at 4-degrees-C or ambient temperature or plasma for a median of 267 days (range, 259 to 482) at -70-degrees-C. The detection of genomic HIV-1 RNA encapsulated in viral particles was very consistent, reproducible, and unaffected by either heparin or acid citrate or by multiple freeze-thawing. The HIV-1 RNA titers also appeared to generally correlate with the biologic titer obtained by the microculture assay. The consistency in infectious HIV-1 titer was evaluated by using 27 unfrozen plasma specimens collected from five subjects over 1 to 9 days. The median change in HIV-1 titer relative to baseline was -0.5 log10 TCID50/ml (interquartile range, -1.03 to 0.175 log10). In contrast, no significant change in HIV-1 RNA for the same frozen plasma specimens was noted. As such, immunocapture-cDNA-polymerase chain reaction may be a useful measure of plasma viremia for studying the natural history of HIV disease and assessing response to therapy. C1 ABBOTT LABS,RETROVIRUS DIAGNOST,1 ABBOTT PK RD,ABBOTT PK,IL 60064. UNIV WASHINGTON,PACIFIC MED CTR,SEATTLE,WA 98144. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. FU NIAID NIH HHS [UO1-AI-27664] NR 20 TC 64 Z9 64 U1 0 U2 3 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 AUG PY 1993 VL 31 IS 8 BP 1980 EP 1986 PG 7 WC Microbiology SC Microbiology GA LM795 UT WOS:A1993LM79500005 PM 8370724 ER PT J AU GREEN, KY LEW, JF XI, J KAPIKIAN, AZ ESTES, MK AF GREEN, KY LEW, JF XI, J KAPIKIAN, AZ ESTES, MK TI COMPARISON OF THE REACTIVITIES OF BACULOVIRUS-EXPRESSED RECOMBINANT NORWALK VIRUS CAPSID ANTIGEN WITH THOSE OF THE NATIVE NORWALK VIRUS-ANTIGEN IN SEROLOGIC ASSAYS AND SOME EPIDEMIOLOGIC OBSERVATIONS SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID INFECTIOUS NONBACTERIAL GASTROENTERITIS; IMMUNE ELECTRON-MICROSCOPY; ANTIBODIES AB Since the discovery of the Norwalk virus (NV) by immune electron microscopy (IEM) in 1972, serologic studies with this virus have relied on particle-positive fecal material from infected volunteers as the source of antigen because it has not been possible to propagate this virus in cell culture. However, the recent cloning of the W (strain 8FIIa) genome and expression of the capsid protein in a baculovirus system to form ''virus-like particles'' has provided a consistent source of antigen (designated rNV). The purpose of the present study was to compare the antigenicities of these rW particles with those of native W antigen derived from human fecal material by using well-characterized sera obtained from earlier studies. In IEM studies, the rNV antigen reacted with NV-specific antibodies in a manner similar to that observed previously when particle-positive fecal material was used as antigen. In addition, a direct enzyme-linked immunosorbent assay, in which the rW antigen was used as antigen, proved efficient and specific for the detection of serologic responses to W compared with the previously established techniques of IEM and blocking antibody immunoassays in which particle-positive fecal material was used as the antigen. The availability of an unlimited source of antigen will enable serologic studies that will greatly increase our understanding of the epidemiology of W and its role in human enteric illness. C1 BAYLOR COLL MED,DIV MOLEC VIROL,HOUSTON,TX 77030. RP GREEN, KY (reprint author), NIAID,INFECT DIS LAB,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [UOI AI 30448] NR 30 TC 151 Z9 157 U1 0 U2 9 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 AUG PY 1993 VL 31 IS 8 BP 2185 EP 2191 PG 7 WC Microbiology SC Microbiology GA LM795 UT WOS:A1993LM79500041 PM 8396590 ER PT J AU GUNASENA, S NAKAGOMI, O ISEGAWA, Y KAGA, E NAKAGOMI, T STEELE, AD FLORES, J UEDA, S AF GUNASENA, S NAKAGOMI, O ISEGAWA, Y KAGA, E NAKAGOMI, T STEELE, AD FLORES, J UEDA, S TI RELATIVE FREQUENCY OF VP4 GENE ALLELES AMONG HUMAN ROTAVIRUSES RECOVERED OVER A 10-YEAR PERIOD (1982-1991) FROM JAPANESE CHILDREN WITH DIARRHEA SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Note ID POLYMERASE CHAIN-REACTION; IDENTIFICATION; NEUTRALIZATION; SPECIFICITIES; SEROTYPES; RNA AB The relative frequencies of the Wa (corresponding to serotype P1A), DS-1 (P1B), M37 (P2), and AU-1 (P3) alleles of the VP4 gene from rotaviruses collected from the stools of individuals in Japan between 1982 and 1991 were determined to be 83.1, 15.6, 0, and 1.3%, respectively, by a polymerase chain reaction-based typing assay. C1 AKITA UNIV, SCH MED, DEPT LAB MED, AKITA 010, JAPAN. AKITA UNIV, SCH MED, DEPT MICROBIOL, AKITA 010, JAPAN. OSAKA UNIV, MICROBIAL DIS RES INST, DEPT PREVENT MED, SUITA 560, JAPAN. NIAID, INFECT DIS LAB, BETHESDA, MD 20892 USA. NR 12 TC 49 Z9 49 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 EI 1098-660X J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD AUG PY 1993 VL 31 IS 8 BP 2195 EP 2197 PG 3 WC Microbiology SC Microbiology GA LM795 UT WOS:A1993LM79500043 PM 8396591 ER PT J AU SOSMAN, JA WEISS, GR MARGOLIN, KA ARONSON, FR SZNOL, M ATKINS, MB OBOYLE, K FISHER, RI BOLDT, DH DOROSHOW, J ERNEST, ML FISHER, SG MIER, J VACHINO, G CALIENDO, G AF SOSMAN, JA WEISS, GR MARGOLIN, KA ARONSON, FR SZNOL, M ATKINS, MB OBOYLE, K FISHER, RI BOLDT, DH DOROSHOW, J ERNEST, ML FISHER, SG MIER, J VACHINO, G CALIENDO, G TI PHASE-IB CLINICAL-TRIAL OF ANTI-CD3 FOLLOWED BY HIGH-DOSE BOLUS INTERLEUKIN-2 IN PATIENTS WITH METASTATIC MELANOMA AND ADVANCED RENAL-CELL CARCINOMA - CLINICAL AND IMMUNOLOGICAL EFFECTS SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACTIVATED KILLER CELLS; TUMOR-INFILTRATING LYMPHOCYTES; T-CELL; MONOCLONAL-ANTIBODY; RECOMBINANT INTERLEUKIN-2; CANCER-PATIENTS; MALIGNANT-MELANOMA; ADOPTIVE IMMUNOTHERAPY; CYTOLYTIC ACTIVITY; NECROSIS FACTOR C1 UNIV TEXAS,HLTH SCI CTR,AUDIE MURPHY VET ADM MED CTR,SAN ANTONIO,TX 78284. CITY HOPE NATL MED CTR,DUARTE,CA 91010. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. TUFTS UNIV,NEW ENGLAND MED CTR,BOSTON,MA 02111. NCI,DIV CANC TREATMENT,INVEST DRUG BRANCH,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892. MONTEFIORE MED CTR,ALBERT EINSTEIN MED CTR,BRONX,NY 10467. RP SOSMAN, JA (reprint author), LOYOLA UNIV,MED CTR,EXTRAMURAL IL-2 WORKING GRP,2160 S 1ST AVE,MAYWOOD,IL 60153, USA. FU NCI NIH HHS [N01-CM-73704] NR 60 TC 34 Z9 34 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 AUG PY 1993 VL 11 IS 8 BP 1496 EP 1505 PG 10 WC Oncology SC Oncology GA LR480 UT WOS:A1993LR48000010 PM 8336188 ER PT J AU WILSON, WH BRYANT, G BATES, S FOJO, A WITTES, RE STEINBERG, SM KOHLER, DR JAFFE, ES HERDT, J CHESON, BD CHABNER, BA AF WILSON, WH BRYANT, G BATES, S FOJO, A WITTES, RE STEINBERG, SM KOHLER, DR JAFFE, ES HERDT, J CHESON, BD CHABNER, BA TI EPOCH CHEMOTHERAPY - TOXICITY AND EFFICACY IN RELAPSED AND REFRACTORY NON-HODGKINS-LYMPHOMA SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LARGE-CELL LYMPHOMA; P-GLYCOPROTEIN EXPRESSION; SOUTHWEST-ONCOLOGY-GROUP; PHASE-II TRIAL; COMBINATION CHEMOTHERAPY; MALIGNANT-LYMPHOMAS; INTERMEDIATE-GRADE; MACOP-B; REGIMEN; RESISTANCE C1 NCI,MED BRANCH,BETHESDA,MD 20892. NR 33 TC 187 Z9 194 U1 0 U2 4 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 AUG PY 1993 VL 11 IS 8 BP 1573 EP 1582 PG 10 WC Oncology SC Oncology GA LR480 UT WOS:A1993LR48000021 PM 7687667 ER PT J AU ROSENSTEIN, DL NELSON, JC JACOBS, SC AF ROSENSTEIN, DL NELSON, JC JACOBS, SC TI SEIZURES ASSOCIATED WITH ANTIDEPRESSANTS - A REVIEW SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Review ID PLASMA DRUG CONCENTRATIONS; GRAND-MAL SEIZURES; MAPROTILINE HYDROCHLORIDE; TRICYCLIC ANTIDEPRESSANTS; CONVULSIVE SEIZURES; FLUOXETINE THERAPY; CLINICAL-FEATURES; ADVERSE REACTIONS; BUPROPION; OVERDOSE AB Background: Seizures are uncommon, but serious, adverse effects of antidepressant drugs. A better understanding of drug-related seizure risk, its predictors, and its neurophysiologic basis might help clinicians avoid this adverse event. A better understanding of the factors involved in the determination of seizure risk would be helpful for interpretation of seizure rates reported. Method. The authors review case reports, series of cases, and information from clinical trials of antidepressants to determine antidepressant-related seizure risk. Predisposing factors are identified. Effects of dose, blood levels, and duration of treatment on seizure risk are examined. Electrophysiologic and in vitro models of drug-related seizure induction are discussed. Results: A significant proportion of drug-related seizures occurs in individuals with an identifiable predisposition, such as previous seizures, sedative or alcohol withdrawal, and multiple concomitant medications. Seizure risk for most antidepressants increases with dose (or blood level), and comparisons between drugs should consider seizure rates at the effective dose (or blood level) for each drug. For imipramine, the most frequently studied tricyclic, the literature indicates a seizure rate between 0.3% and 0.6% at effective doses. In unselected patients and at higher doses, these rates may be higher. Fluoxetine, sertraline, fluvoxamine, trazodone, nomifensine, and the monoamine oxidase inhibitors have a lower seizure risk. Estimates for recently marketed antidepressants with intermediate seizure risk are complicated by the fact that effective doses and blood levels are not well established. Conclusion: Assessment of seizure risk in individuals involves consideration of predisposing factors, the antidepressant selected, and the bioavailability of the drug. Future studies of seizure risk would benefit from the use of specified criteria for determination of probable seizure events, a priori definition of predisposing exclusions, samples sufficiently large to provide adequate power, blood level monitoring, and inclusion of duration of drug treatment in the calculation of risk. C1 NIMH,BETHESDA,MD 20892. YALE UNIV,SCH MED,DEPT PSYCHIAT,NEW HAVEN,CT 06510. NR 93 TC 169 Z9 169 U1 0 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD AUG PY 1993 VL 54 IS 8 BP 289 EP 299 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA MF660 UT WOS:A1993MF66000002 PM 8253696 ER PT J AU LITMAN, RE HONG, WW WEISSMAN, EM SU, TP POTTER, WZ PICKAR, D AF LITMAN, RE HONG, WW WEISSMAN, EM SU, TP POTTER, WZ PICKAR, D TI IDAZOXAN, AN ALPHA-2 ANTAGONIST, AUGMENTS FLUPHENAZINE IN SCHIZOPHRENIC-PATIENTS - A PILOT-STUDY SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID VENTRAL TEGMENTAL AREA; DOPAMINE RECEPTOR; CLOZAPINE; SYMPTOMS; RAT AB Idazoxan, a selective alpha2-adrenergic antagonist, was added to stable doses of fluphenazine treatment in six patients with schizophrenia who participated in a double-blind, placebo-controlled pharmacologic study. Compared with fluphenazine alone, combining idazoxan (mean dose, 120 mg/day) with fluphenazine (mean dose, 28 mg/day) resulted in a significant decrease in Brief Psychiatric Rating Scale total symptoms (p < 0.05). Symptom ratings returned to baseline upon idazoxan discontinuation. No significant effects of idazoxan were observed on fluphenazine levels in plasma or on extrapyramidal symptoms. These pilot data are compatible with the notion that increased noradrenergic neurotransmission may enhance the therapeutic effects of typical neuroleptics in schizophrenia. RP LITMAN, RE (reprint author), NIMH,CLIN STUDIES SECT,EXPTL THERAPEUT BRANCH,NIH BLDG 10-4N214,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 20 TC 48 Z9 48 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD AUG PY 1993 VL 13 IS 4 BP 264 EP 267 PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA LM936 UT WOS:A1993LM93600006 PM 8104200 ER PT J AU DISTLER, C BOUSSAOUD, D DESIMONE, R UNGERLEIDER, LG AF DISTLER, C BOUSSAOUD, D DESIMONE, R UNGERLEIDER, LG TI CORTICAL CONNECTIONS OF INFERIOR TEMPORAL AREA TEO IN MACAQUE MONKEYS SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE INFERIOR TEMPORAL CORTEX; EXTRASTRIATE CORTEX; VISUAL SYSTEM; PATTERN VISION ID MARMOSET CALLITHRIX-JACCHUS; POSTERIOR PARIETAL CORTEX; STRIATE PROJECTION ZONE; FRONTAL EYE FIELDS; VISUAL AREA; RHESUS-MONKEY; VISUOTOPIC ORGANIZATION; OWL MONKEYS; TOPOGRAPHIC ORGANIZATION; SQUIRREL-MONKEY AB In macaque monkeys, lesions involving the posterior portion of the inferior temporal cortex, cytoarchitectonic area TEO, produce a severe impairment in visual pattern discrimination. Recently, this area has been shown to contain a complete, though coarse, representation of the contralateral visual field (Boussaoud, Desimone, and Ungerleider: J. Comp. Neurol. 306:554--575, '91). Because the inputs and outputs of area TEO have not yet been fully described, we injected a variety of retrograde and anterograde tracers into 11 physiologically identified sites within TEO of seven rhesus monkeys and analyzed the areal and laminar distribution of its cortical connections. Our results show that TEO receives feedforward, topographically organized inputs from prestriate areas V2, V3, and V4. Additional sparser feedforward inputs arise from areas V3A, V4t, and MT. Each of these inputs is reciprocated by a feedback projection from TEO. TEO was also found to have reciprocal intermediate-type connections with the fundus of the superior temporal area (area FST), cortex in the most posteromedial portion of the superior temporal sulcus (the posterior parietal sulcal zone [area PP]), cortex in the intraparietal sulcus (including the lateral intraparietal area [area LIP]), the frontal eye field, and area TF on the parahippocampal gyrus. The connections with V3A, V4t, and PP were found only after injections in the peripheral field representations of TEO. Finally, TEO was found to project in a feedforward pattern to area TE and to areas anterior to FST on the lateral bank and floor of the superior temporal sulcus (areas TEm, TEa, and IPa, Seltzer and Pandya: Brain Res. 149:1-24, '78), all of which send feedback projections to TEO. Feedback projections also arise from parahippocampal area TH, and areas TG, 36, and possibly 35. These are complemented by only sparse feedforward projections to TG from central field representations in TEO and to TH from peripheral field representations. The results thus indicate that TEO forms an important link in the occipitotemporal pathway for object recognition, sending visual information forward from V1 and prestriate relays in V2-V4 to anterior inferior temporal area TE. (C) 1993 Wiley-Liss, Inc.* C1 NIMH,NEUROPSYCHOL LAB,BLDG 49,ROOM 1B80,BETHESDA,MD 20892. RI Boussaoud, Driss/B-6932-2008 NR 107 TC 207 Z9 208 U1 0 U2 7 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD AUG 1 PY 1993 VL 334 IS 1 BP 125 EP 150 DI 10.1002/cne.903340111 PG 26 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA LN609 UT WOS:A1993LN60900010 PM 8408755 ER PT J AU MCCARTNEYFRANCIS, N ALLEN, JB MIZEL, DE ALBINA, JE XIE, QW NATHAN, CF WAHL, SM AF MCCARTNEYFRANCIS, N ALLEN, JB MIZEL, DE ALBINA, JE XIE, QW NATHAN, CF WAHL, SM TI SUPPRESSION OF ARTHRITIS BY AN INHIBITOR OF NITRIC-OXIDE SYNTHASE SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID L-ARGININE; PERITONEAL-MACROPHAGES; REACTIVE NITROGEN; INDUCTION; RAT; ACTIVATION; METABOLISM; GENERATION; CYTOKINES; PATHWAY AB Nitric oxide (NO), a toxic radical gas produced during the metabolism of L-arginine by No synthase (NOS), has been implicated as a mediator of immune and inflammatory responses. A single injection of streptococcal cell wall fragments (SCW) induces the accumulation of inflammatory cells within the synovial tissue and a cell-mediated immune response that leads to destructive lesions. We show here that NO production is elevated in the inflamed joints of SCW-treated rats. Administration of N(G)-monomethyl-L-arginine, an inhibitor of NOS, profoundly reduced the synovial inflammation and tissue damage as measured by an articular index and reflected in the histopathology. These studies implicate the NO pathway in the pathogenesis of an inflammatory arthritis and demonstrate the ability of a NOS inhibitor to modulate the disease. C1 RHODE ISL HOSP, DEPT SURG, PROVIDENCE, RI 02902 USA. CORNELL UNIV, MED CTR, COLL MED, DEPT MED, NEW YORK, NY 10021 USA. RP MCCARTNEYFRANCIS, N (reprint author), NIDR, CELLULAR IMMUNOL SECT, IMMUNOL LAB, BLDG 30, ROOM 327, BETHESDA, MD 20892 USA. NR 28 TC 511 Z9 525 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 1 PY 1993 VL 178 IS 2 BP 749 EP 754 DI 10.1084/jem.178.2.749 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA LP830 UT WOS:A1993LP83000042 PM 7688035 ER PT J AU NAKAGOMI, O ISEGAWA, Y UEDA, S GERNA, G SARASINI, A KAGA, E NAKAGOMI, T FLORES, J AF NAKAGOMI, O ISEGAWA, Y UEDA, S GERNA, G SARASINI, A KAGA, E NAKAGOMI, T FLORES, J TI NUCLEOTIDE-SEQUENCE COMPARISON OF THE VP8-ASTERISK GENE OF ROTAVIRUSES POSSESSING THE AU-1 GENE 4 ALLELE SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID OUTER CAPSID PROTEIN-VP4; RNA-RNA HYBRIDIZATION; SUBGROUP-I; NEUTRALIZATION EPITOPES; FELINE ROTAVIRUS; UNIQUE VP4; STRAINS; GENOGROUPS; IDENTIFICATION; SPECIFICITIES AB Of the five currently recognized alleles of the human rotavirus VP4 gene, the AU-1 allele has captured attention because of its possible non-human origin. The 5' 750 nucleotide region of the VP4 gene, encoding the VP8* fragment [amino acids (aa) 1 to 241] and the connecting peptide (aa 242 to 247), from 13 human and two feline rotavirus strains possessing the AU-1 allele was highly conserved both at the nucleotide sequence (93.8 to 99.7% identity) and amino acid level (95.5 to 100 % identity) irrespective of the year and the place of isolation or of the host species from which these viruses were isolated. This is consistent with the hypothesis that the AU-1 allele of the VP4 gene has been maintained in both human and feline rotavirus gene pools. C1 AKITA UNIV,SCH MED,DEPT LAB MED,AKITA 010,JAPAN. OSAKA UNIV,DEPT PREVENT MED,MICROBIAL DIS RES INST,SUITA,OSAKA 565,JAPAN. UNIV PAVIA,INST INFECT DIS,VIRUS LAB,I-27100 PAVIA,ITALY. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. RP NAKAGOMI, O (reprint author), AKITA UNIV,SCH MED,DEPT MICROBIOL,1-1-1 HONDO,AKITA 010,JAPAN. NR 30 TC 11 Z9 12 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 AUG PY 1993 VL 74 BP 1709 EP 1713 DI 10.1099/0022-1317-74-8-1709 PN 8 PG 5 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA LQ264 UT WOS:A1993LQ26400033 PM 8393919 ER PT J AU DING, L LINSLEY, PS HUANG, LY GERMAIN, RN SHEVACH, EM AF DING, L LINSLEY, PS HUANG, LY GERMAIN, RN SHEVACH, EM TI IL-10 INHIBITS MACROPHAGE COSTIMULATORY ACTIVITY BY SELECTIVELY INHIBITING THE UP-REGULATION OF B7 EXPRESSION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL PROLIFERATION; HEAT-STABLE ANTIGEN; CYTOKINE PRODUCTION; ACTIVATED MACROPHAGES; MONOCLONAL-ANTIBODIES; MURINE-B7 ANTIGEN; LYMPHOCYTES-T; IFN-GAMMA; INTERLEUKIN-10; MOLECULE AB We have previously demonstrated that the inhibitory effects of IL-10 on ConA-induced T cell proliferation or IL-2 production by resting murine T cells were only observed when macrophages, but not when activated B cells, dendritic cells, or L cells, were used as accessory cells. To further elucidate the mechanism of action of IL-10 on the inhibition of macrophage costimulatory activity, we have used a system in which macrophages can develop into effective costimulator cells and the effect of IL-10 on this process can be studied in the absence of T cells. After fixation, resting macrophages have no costimulatory activity for soluble anti-CD3-induced T cell proliferation nor do they express the activation Ag B7/BB1. In contrast, macrophages activated by culture alone, or by culture with IFN-gamma or LPS for 24 h, and then fixed, were effective accessory cells, expressed B7, and their costimulatory activity correlated with their level of cell surface B7 expression. Addition of IL-10 during the process of macrophage activation resulted in both a marked reduction in costimulatory activity and in B7 expression. IL-4 and transforming growth factor-beta that suppress many macrophage functions did not inhibit the induction-of B7 expression. The inhibitory effect of IL-10 on the up-regulation of B7 was selective because the up-regulation of intercellular adhesion molecule-1 and MHC class II Ag was not affected. Direct evidence that the lack of B7 is the relevant limiting defect for IL-10-treated macrophage accessory cell function was obtained from studies in which the costimulatory capacity of IL-10-treated macrophages could be completely restored by the addition of B7 transfected, but not nontransfected, L cells to the assays. C1 NIAID,IMMUNOL LAB,BLDG 10,ROOM 11N-315,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. BRISTOL MEYERS SQUIBB,PHARMACEUT RES INST,SEATTLE,WA 98121. NR 50 TC 737 Z9 755 U1 1 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 1993 VL 151 IS 3 BP 1224 EP 1234 PG 11 WC Immunology SC Immunology GA LP725 UT WOS:A1993LP72500006 PM 7687627 ER PT J AU VACCHIO, MS GRANGER, L KANAGAWA, O MALISSEN, B TOMONARI, K SHARROW, SO HODES, RJ AF VACCHIO, MS GRANGER, L KANAGAWA, O MALISSEN, B TOMONARI, K SHARROW, SO HODES, RJ TI T-CELL RECEPTOR V-ALPHA-V-BETA COMBINATORIAL SELECTION IN THE EXPRESSED T-CELL REPERTOIRE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTIGEN RECEPTOR; MONOCLONAL-ANTIBODIES; POSITIVE SELECTION; NEGATIVE SELECTION; TRANSGENIC MICE; GENE-PRODUCTS; MOUSE STRAINS; I-E; RECOGNITION; REACTIVITY AB This study has evaluated whether preferential pairing occurs between TCR alpha- and beta-chains expressing specific Valpha and Vbeta gene products in the mature peripheral T cell population, as a result of either thymic selection or of structural constraints on chain pairing. The association of specific Valpha products with specific Vbeta products on individual T cells was found, in multiple instances, to be highly selective. Moreover, patterns of preferential Valpha-Vbeta association were highly strain-specific and were independently expressed in CD4+ and CD8+ T cell subsets. Although these findings do not exclude the possibility that structural constraints may limit Valpha-Vbeta pairing in other instances, they indicate that the observed instances of skewed expression are not caused by structural constraints in chain pairing. Rather, they suggest that strain-specific selective events alter the expressed ValphaVbeta repertoire as a result of recognition of self or environmental Ag during T cell repertoire selection. C1 WASHINGTON UNIV,SCH MED,DEPT PATHOL,ST LOUIS,MO 63110. MRC,CTR CLIN RES,IMMUNOL MED SECT,HARROW HA1 3UJ,MIDDX,ENGLAND. CTR IMMUNOL MARSEILLE LUMINY,MARSEILLE,FRANCE. RP VACCHIO, MS (reprint author), NCI,BIOL RESPONSE MODIFIERS PROGRAM,BLDG 10,RM 1B40,BETHESDA,MD 20892, USA. NR 30 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 AUG 1 PY 1993 VL 151 IS 3 BP 1322 EP 1327 PG 6 WC Immunology SC Immunology GA LP725 UT WOS:A1993LP72500016 PM 8101542 ER PT J AU GUSTAFSSON, K GERMANA, S SUNDT, TM SACHS, DH LEGUERN, C AF GUSTAFSSON, K GERMANA, S SUNDT, TM SACHS, DH LEGUERN, C TI EXTENSIVE ALLELIC POLYMORPHISM IN THE CDR2-LIKE REGION OF THE MINIATURE SWINE CD4 MOLECULE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MAJOR HISTOCOMPATIBILITY COMPLEX; ANTIGEN-PRESENTING CELLS; CLASS-II MHC; MONOCLONAL-ANTIBODIES; ENVELOPE GLYCOPROTEIN; MUTATIONAL ANALYSIS; STRUCTURAL-ANALYSIS; GP120 BINDING; HIV-1 GP120 AB MHC class II polymorphism is well documented whereas only minimal polymorphism has been reported for the CD4 molecule with which it interacts. We report on the structural basis of an allelic polymorphism of the CD4 molecule in miniature swine. Eleven of 13 nucleotide differences between the 2 alleles cause amino acid replacements. A majority of these replacements are clustered in a region protruding as a loop structure, termed Ig CDR2-like, from the surface of the amino terminal domain. This part of the human CD4 appears to comprise the binding site for the human immunodeficiency virus gp120 protein. The loop structure has also been implicated in the binding of CD4 to MHC class II, but this is currently a matter of some controversy. Our previous results have indicated that the porcine CD4 polymorphism, that we now show is situated in this loop, does not significantly affect the binding to class II. However, because the polymorphism appears to have been selected for and is situated in a very exposed part of the molecule, it is likely to be of functional significance. C1 MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,MGH-E,BLDG 149,13TH ST,BOSTON,MA 02129. NCI,TRANSPLANTAT BIOL SECT,IMMUNOL BRANCH,BETHESDA,MD 20892. NR 30 TC 18 Z9 20 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 1993 VL 151 IS 3 BP 1365 EP 1370 PG 6 WC Immunology SC Immunology GA LP725 UT WOS:A1993LP72500021 PM 8335933 ER PT J AU ONEIL, BH KAWAKAMI, Y RESTIFO, NP BENNINK, JR YEWDELL, JW ROSENBERG, SA AF ONEIL, BH KAWAKAMI, Y RESTIFO, NP BENNINK, JR YEWDELL, JW ROSENBERG, SA TI DETECTION OF SHARED MHC-RESTRICTED HUMAN-MELANOMA ANTIGENS AFTER VACCINIA VIRUS-MEDIATED TRANSDUCTION OF GENES-CODING FOR HLA SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; AUTOLOGOUS MELANOMA; T-CELLS; RECOGNITION; IMMUNOTHERAPY; INTERLEUKIN-2; EXPRESSION AB To detect shared human melanoma Ag that are recognized by HLA-A2 restricted, melanoma-specific CTL derived from tumor infiltrating lymphocytes, we have developed a convenient method to insert and express foreign HLA genes capable of presenting Ag on target cell lines. Seventeen melanoma cell lines and 11 nonmelanoma cell lines were infected with recombinant vaccinia virus containing the HLA-A2.1 gene. Infection by the vaccinia virus resulted in expression of functional HLA-A2 molecules on the cell surface of virtually 100% of infected cells within a 3.5-h period. The results showed that 11 of 17 (65%) naturally HLA-A2- melanoma cell lines were specifically lysed by the HLA-A2-restricted, melanoma-specfic TIL after infection with the vaccinia-HLA-A2.1 virus. None of the nine human nonmelanoma cell lines tested (three colon cancer, four breast cancer, or two immortalized non-tumor cell lines) or two murine melanoma cell lines were lysed by the HLA-A2-restricted TIL after vaccinia-HLA-A2.1 infection. Coinfection of the vaccinia virus containing the beta2-microglobulin gene with the vaccinia-HLA-A2.1 virus increased the surface expression of HLA-A2 and subsequent lysis by melanoma-specific tumor infiltrating lymphocytes. With this new method we could extend previous findings demonstrating that shared melanoma Ag recognized by HLA-A2-restricted tumor infiltrating lymphocytes exist among melanoma cells from different patients regardless of HLA type. These Ag represent excellent candidates for the development of vaccines to induce T cell responses for the immunotherapy of patients with melanoma. C1 NCI,SURG BRANCH,BLDG 10,RM 2B42,BETHESDA,MD 20892. NIAID,BIOCHEM LAB,BETHESDA,MD 20892. RI Restifo, Nicholas/A-5713-2008; yewdell, jyewdell@nih.gov/A-1702-2012; Kawakami, Yutaka /E-7429-2013; OI Kawakami, Yutaka /0000-0003-4836-2855; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 26 TC 44 Z9 44 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 AUG 1 PY 1993 VL 151 IS 3 BP 1410 EP 1418 PG 9 WC Immunology SC Immunology GA LP725 UT WOS:A1993LP72500026 PM 8335937 ER PT J AU WYNN, TA ELTOUM, I CHEEVER, AW LEWIS, FA GAUSE, WC SHER, A AF WYNN, TA ELTOUM, I CHEEVER, AW LEWIS, FA GAUSE, WC SHER, A TI ANALYSIS OF CYTOKINE MESSENGER-RNA EXPRESSION DURING PRIMARY GRANULOMA-FORMATION INDUCED BY EGGS OF SCHISTOSOMA-MANSONI SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; INVIVO MOLECULAR ANALYSIS; MURINE IMMUNE-RESPONSE; MESENTERIC LYMPH-NODES; INFECTED MICE; INTERFERON-GAMMA; LYMPHOCYTES-T; GOAT ANTIBODY; IFN-GAMMA; MOUSE IGD AB Granulomas induced by parasite eggs are the primary lesions in mice infected with Schistosoma mansoni. Temporal analysis of cytokine mRNA expression in lung tissue containing synchronized granulomas demonstrated a Th0-like pattern of lymphokine expression. IFN-gamma, IL-1beta, and IL-6 were the primary cytokines induced by day 1 in developing lung granulomas initiated by i.v. egg injection. These changes were followed by increases in expression of IL-2, IL-4, and IL-10 mRNA on day 3 and TNF-alpha and IL-5 mRNA on day 6. Nearly all cytokine mRNA reached maximal levels by day 6, which preceded the peak in granuloma size seen on day 14. In vivo treatment of egg-injected mice with either anti-IL-2 or anti-IL-4 antibodies significantly diminished the size of circumoval granulomas in the lungs. Both groups of antibody-treated animals displayed a marked reduction in IL-4 as well as IL-5 mRNA expression, although IFN-gamma and IL-2 mRNA levels were unchanged or slightly increased. These findings confirm previous observations suggesting a role for IL-2 in egg-induced pathology via the generation of Th2-associated responses, and also indicate a primary function for IL-4 in granuloma formation. Analysis of responses after injection of eggs into nude mice demonstrated that only the Th2 cytokines IL-4 and IL-5 are exclusively dependent on T cells for their induction. Taken together, these data suggest that Th2 cells producing IL-4 play a major role in egg granuloma formation, and that the induction and ultimate down-modulation of Th2-like responses may be influenced by non-T-cell-derived cytokines. C1 NIAID,HOST PARASITE RELAT SECT,BETHESDA,MD 20892. BIOMED RES INST,ROCKVILLE,MD 20852. UNIFORMED SERV UNIV HLTH SCI,DEPT MICROBIOL,BETHESDA,MD 20814. RP WYNN, TA (reprint author), NIAID,IMMUNOL & CELL BIOL SECT,PARASIT DIS LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Wynn, Thomas/C-2797-2011 NR 41 TC 332 Z9 338 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 AUG 1 PY 1993 VL 151 IS 3 BP 1430 EP 1440 PG 11 WC Immunology SC Immunology GA LP725 UT WOS:A1993LP72500028 PM 8335939 ER PT J AU ATKINSON, TP LEE, CW RHEE, SG HOHMAN, RJ AF ATKINSON, TP LEE, CW RHEE, SG HOHMAN, RJ TI ORTHOVANADATE INDUCES TRANSLOCATION OF PHOSPHOLIPASE-C-GAMMA-1 AND C-GAMMA-2 IN PERMEABILIZED MAST-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BASOPHILIC LEUKEMIA-CELLS; HIGH-AFFINITY RECEPTOR; INDUCED TYROSINE PHOSPHORYLATION; MEDIATED SIGNAL TRANSDUCTION; STAPHYLOCOCCAL ALPHA-TOXIN; EPIDERMAL GROWTH-FACTOR; PROTEIN-KINASE-C; HISTAMINE-RELEASE; IGE RECEPTORS; MEMBRANE AB Rapid activation of phospholipase C (PLC) with a resultant increase in phosphatidylinositol hydrolysis occurs after aggregation of the high affinity receptor for IgE (FcepsilonRI) on the surface of mast cells. We previously described an increase in PLC activity associated with the particulate fraction of rat basophilic leukemia (RBL) cells after FcepsilonRI aggregation, and this redistribution of enzyme activity correlated with an increase in immunoreactivity of the gamma1 isozyme of PLC in the particulate fraction by Western blot analysis (J. Immunol. 148:2194-2200, 1992). We now report that the tyrosine phosphatase inhibitor orthovanadate mimics FcepsilonRI-mediated activation of PLC-gamma1 in RBL cells after permeabilization with Staphylococcus aureus alpha-toxin. Orthovanadate treatment of permeabilized cells induced: 1) a large increase in phosphoinositide hydrolysis in endogenously labeled cells; 2) an increase in PLC activity associated with the particulate fraction; and 3) an increase in immunoreactivity of PLC-gamma1 in Western blots of the particulate fraction. In addition, incubation of RBL cells with either oligomeric IgE or orthovanadate results in the translocation of PLC-gamma2 from the cytosol to the particulate fraction. All of the above effects were qualitatively similar to those seen after FcepsilonRI aggregation. These data suggest that translocation and activation of PLC in mast cells are controlled by tyrosine phosphorylation of either the enzyme itself or some regulatory component. The equilibrium can be shifted to the phosphorylated state during either receptor-mediated activation of a tyrosine kinase or by blockade of dephosphorylation. C1 NIAID,ALLERG DIS SECT,CLIN INVEST LAB,BETHESDA,MD 20892. NHLBI,SIGNAL TRANSDUCT SECT,BIOCHEM LAB,BETHESDA,MD 20892. NR 43 TC 28 Z9 28 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 AUG 1 PY 1993 VL 151 IS 3 BP 1448 EP 1455 PG 8 WC Immunology SC Immunology GA LP725 UT WOS:A1993LP72500030 PM 7687631 ER PT J AU CROFFORD, LJ SANO, H KARALIS, K FRIEDMAN, TC EPPS, HR REMMERS, EF MATHERN, P CHROUSOS, GP WILDER, RL AF CROFFORD, LJ SANO, H KARALIS, K FRIEDMAN, TC EPPS, HR REMMERS, EF MATHERN, P CHROUSOS, GP WILDER, RL TI CORTICOTROPIN-RELEASING HORMONE IN SYNOVIAL-FLUIDS AND TISSUES OF PATIENTS WITH RHEUMATOID-ARTHRITIS AND OSTEOARTHRITIS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PITUITARY-ADRENAL AXIS; RAT SPINAL-CORD; SUBSTANCE-P; GROWTH-FACTOR; IMMUNOREACTIVE CORTICOTROPIN; INTERLEUKIN-6 PRODUCTION; SYMPATHETIC EFFERENTS; MONONUCLEAR-CELLS; OSTEO-ARTHRITIS; FACTOR CRF AB Inflammation normally results in enhanced synthesis and secretion of hypothalamic corticotropin releasing hormone (CRH) which, in turn, exerts antiinflammatory effects by virtue of increased adrenal glucocorticoid production. CRH and CRH binding sites are also expressed in the peripheral nervous and immune systems. Our groups have recently shown that CRH is secreted locally in acute carrageenin-induced inflammation in rats and has predominantly proinflammatory effects. We have also shown that CRH is expressed in the joints of Lewis rats with experimental arthritis. To determine if CRH is present in human inflammatory arthritis, we examined synovial fluids and tissues from patients with rheumatoid arthritis (RA) or osteoarthritis (OA) and normal individuals. We found markedly enhanced expression of immunoreactive CRH in situ in synovium from patients, which was significantly greater in RA than in OA (p < 0.01). CRH concentrations were also significantly higher in RA (140 +/- 33 pg/ml, mean +/- SEM; n = 10) than OA (25 +/- 4 pg/ml; n = 6) synovial fluids (p < 0.005). HPLC showed immunoreactive CRH extracted from RA and OA synovial tissues and fluids coeluted with CRH 1-41. CRH mRNA was present in low levels in synovial tissue from patients with RA and, to a lesser extent, OA. In summary, immunoreactive CRH is locally secreted in the synovium of patients with RA and, at lower levels, OA. These data support the view that CRH functions as an autocrine and/or paracrine mediator of inflammation in humans. C1 NICHHD, DEV NEUROBIOL LAB, BETHESDA, MD 20892 USA. RP CROFFORD, LJ (reprint author), NIAMSD, INFLAMMATORY JOINT DIS SECT, ARTHRIT & RHEUMATISM BRANCH, BLDG 10, RM 9N240, BETHESDA, MD 20892 USA. RI Crofford, Leslie/J-8010-2013 NR 52 TC 146 Z9 146 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 1993 VL 151 IS 3 BP 1587 EP 1596 PG 10 WC Immunology SC Immunology GA LP725 UT WOS:A1993LP72500045 PM 8335947 ER PT J AU EGWUAGU, CE MAHDI, RM NUSSENBLATT, RB GERY, I CASPI, RR AF EGWUAGU, CE MAHDI, RM NUSSENBLATT, RB GERY, I CASPI, RR TI EVIDENCE FOR SELECTIVE ACCUMULATION OF V-BETA-8+ T-LYMPHOCYTES IN EXPERIMENTAL AUTOIMMUNE UVEORETINITIS INDUCED WITH 2 DIFFERENT RETINAL ANTIGENS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID V-BETA GENES; BINDING PROTEIN IRBP; CELL RECEPTOR; S-ANTIGEN; ENCEPHALITOGENIC DETERMINANT; CHAIN USAGE; RAT; ENCEPHALOMYELITIS; UVEITIS; DISEASE AB Experimental autoimmune uveoretinitis (EAU) is a T cell-mediated autoimmune disease that serves as a model of human intraocular inflammatory disease (uveitis) and is initiated in susceptible animals by immunization with retinal Ag, such as interphotoreceptor retinoid binding protein (IRBP) and S-Ag (SAg). Previous studies of TCR usage by uveitogenic T cells suggested a possible connection between pathogenicity of T lymphocytes and usage of Vbeta8 family genes. Here, we have analyzed the T cell repertoire at the autoimmune site by examining Vbeta gene expression in the retinas of rats with SAg- or IRBP-induced uveitis. Our data show the following: 1) T cell response to SAg or IRBP is clonally heterogeneous: at least 15 of the 20 known rat TCR families were detected in the retinas of rats with EAU. 2) Vbeta8+ T cells were selectively increased in retina during the early stage of EAU, and the pattern of Vbeta8 subfamily member utilization in the retina was Ag-dependent: Vbeta8.2+ and Vbeta8.3+ T cells were found in the retina of rats immunized with IRBP but only Vbeta8.2+ cells in SAg-induced EAU. Vbeta8.1 cells were not detected in any of the samples. 3) Kinetic change in the proportions of Vbeta8.2+ and Vbeta8.3+ T cells was observed in IRBP-EAU: on the day of clinical onset of disease, Vbeta8.3+ cells were the only member of the Vbeta8 family detected, but 24 h later, Vbeta8.2+ T cells appeared and became the dominant Vbeta8 clonotype in the retina. 4) The pattern of Vbeta8 family member usage by T cells in uveitogenic lines specific to the corresponding Ag was similar to their utilization in the uveitic response in the retina. DNA sequence analysis of 75 Vbeta8 cDNA clones from uveitogenic T cell lines revealed that, of 20 Vbeta8 clones isolated from SAg-specific T cell lines, all were Vbeta8.2 TCR, whereas among 55 Vbeta8 clones from IRBP-specific lines, 36 were Vbeta8.2 and 19 were Vbeta8.3. In similarity to the retina, no Vbeta8.1+ T cells were detected from these T cell lines. Taken together, our data suggest a bias towards usage of Vbeta8+ cells in EAU and, depending on the autoantigen mediating the disease, particular Vbeta8 subfamily member(s) were preferentially utilized or excluded from the autoimmune response. RP EGWUAGU, CE (reprint author), NEI, IMMUNOL LAB, BLDG 10 10B10, BETHESDA, MD 20892 USA. NR 37 TC 32 Z9 32 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 1993 VL 151 IS 3 BP 1627 EP 1636 PG 10 WC Immunology SC Immunology GA LP725 UT WOS:A1993LP72500049 PM 8393049 ER PT J AU SELVEY, LA MORSE, HC GRANGER, LG HODES, RJ AF SELVEY, LA MORSE, HC GRANGER, LG HODES, RJ TI PREFERENTIAL EXPANSION AND ACTIVATION OF V-BETA-5+ CD4+ T-CELLS IN MURINE ACQUIRED-IMMUNODEFICIENCY-SYNDROME SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RETROVIRUS-INDUCED IMMUNODEFICIENCY; MAMMARY-TUMOR VIRUS; MONOCLONAL-ANTIBODIES; LYMPHOCYTES-T; SUPERANTIGEN; EXPRESSION; MAIDS; ANTIGEN; MOUSE; MICE AB Infection of B6 mice with LP-BM5 MuLV results in a syndrome characterized by progressive and profound immunodeficiency, termed murine acquired immunodeficiency syndrome (MAIDS). In this report we show that preferential expansion and activation of Vbeta5+ CD4+ spleen cells occurs early in the course of disease, which then progresses to more widespread polyclonal activation of CD4+ T cells. Vbeta5 expansion occurs only on infection with MAIDS-associated MuLV and is not observed after infection with other MuLV. The possible role of Vbeta5 activation and expansion as a necessary early step in the pathogenesis of MAIDS is discussed. C1 NIAID,IMMUNOPATHOL LAB,BETHESDA,MD 20892. RP SELVEY, LA (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,RM 4B17,BETHESDA,MD 20892, USA. RI Selvey, Linda/B-8473-2017; OI Selvey, Linda/0000-0001-8493-0974; Morse, Herbert/0000-0002-9331-3705 NR 37 TC 31 Z9 31 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 AUG 1 PY 1993 VL 151 IS 3 BP 1712 EP 1722 PG 11 WC Immunology SC Immunology GA LP725 UT WOS:A1993LP72500058 PM 8101545 ER PT J AU KAWAKAMI, Y NISHIMURA, MI RESTIFO, NP TOPALIAN, SL ONEIL, BH SHILYANSKY, J YANNELLI, JR ROSENBERG, SA AF KAWAKAMI, Y NISHIMURA, MI RESTIFO, NP TOPALIAN, SL ONEIL, BH SHILYANSKY, J YANNELLI, JR ROSENBERG, SA TI T-CELL RECOGNITION OF HUMAN-MELANOMA ANTIGENS SO JOURNAL OF IMMUNOTHERAPY LA English DT Article; Proceedings Paper CT KEYSTONE SYMP ON CELLULAR IMMUNITY AND THE IMMUNOTHERAPY OF CANCER 2 CY MAR 17-24, 1993 CL TAOS, NM DE TUMOR-INFILTRATING LYMPHOCYTES; MELANOMA ANTIGENS; T-CELL RECEPTOR; HLA-A2.1; IMMUNOTHERAPY ID TUMOR-INFILTRATING LYMPHOCYTES; METASTATIC MELANOMA; AUTOLOGOUS MELANOMA; RESTRICTION; ALLELE; LYSIS AB The adoptive transfer of tumor-infiltrating lymphocytes (TILs) with interleukin-2 (IL-2) has antitumor activity in some patients with metastatic melanoma. We have analyzed molecular mechanisms of TIL recognition of human melanoma. Some cultured TILs specifically lysed autologous and some allogeneic melanomas sharing a variety of class I major histocompatibility complex (MHC) molecules. HLA-A2-restricted melanoma-specific TILs lysed many HLA-A2+ melanoma cell lines from different patients but failed to lyse HLA-A2- melanoma and HLA-A2+ nonmelanoma cell lines. However, these TILs were capable of lysing many naturally HLA-A2- melanomas after introduction of the HLA-A2.1 gene by vaccinia virus. These results indicate that shared melanoma antigens (Ag) are expressed in melanomas regardless of their human leukocyte antigen types. In order to identify these shared melanoma Ags, we have tested some known proteins expressed in melanoma. Expression of tyrosinase or HMB45 Ag correlated with lysis of TILs. We are also attempting to isolate antigenic peptides by high performance liquid chromatography separation and genes encoding melanoma Ag by cDNA expression cloning. The T-cell component of the antimelanoma response was also analyzed by determining the genetic structure of the T-cell receptor (TCR) used by melanoma TILs. However, we did not observe common TCR variable region usage by different melanoma TILs. We could establish melanoma cell clones and lines resistant to TIL lysis due to the absence of or defects in the expression of Ag, MHC, or beta2-microglobulin molecules. These data indicate multiple mechanisms for melanoma escape from T-cell immunosurveillance. These findings have important implications for the development of immunotherapies for melanoma. RP KAWAKAMI, Y (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B42,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Restifo, Nicholas/A-5713-2008; Kawakami, Yutaka /E-7429-2013; OI Kawakami, Yutaka /0000-0003-4836-2855; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [NIH0010139353, Z01 BC010763-01, Z99 TW999999] NR 20 TC 47 Z9 49 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD AUG PY 1993 VL 14 IS 2 BP 88 EP 93 DI 10.1097/00002371-199308000-00002 PG 6 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA LZ701 UT WOS:A1993LZ70100002 PM 8280705 ER PT J AU JACOBSON, JM COLMAN, N OSTROW, NA SIMSON, RW TOMESCH, D MARLIN, L RAO, M MILLS, JL CLEMENS, J PRINCE, AM AF JACOBSON, JM COLMAN, N OSTROW, NA SIMSON, RW TOMESCH, D MARLIN, L RAO, M MILLS, JL CLEMENS, J PRINCE, AM TI PASSIVE IMMUNOTHERAPY IN THE TREATMENT OF ADVANCED HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID AIDS-RELATED COMPLEX; ENVELOPE GLYCOPROTEIN GP120; MATERNAL ANTIBODIES; HOMOSEXUAL MEN; HIV-INFECTION; IMMUNIZATION; CHIMPANZEES; PREVENTION; TYPE-1; NEUTRALIZATION AB To evaluate the safety and efficacy of passive immunotherapy for advanced human immunodeficiency virus (HIV) infection, a randomized, double-blind, controlled trial of human anti-HIV hyperimmune plasma was conducted. Sixty-three subjects with stage IV HIV disease (AIDS) were randomized to receive 250 mL of either HIV-immune plasma or HIV antibody-negative plasma every 4 weeks. Although nonsignificant trends toward improved survival and delayed occurrence of a new opportunistic infection were noted, no significant effects on absolute CD4 lymphocyte counts or quantitative HIV viremia were seen. The only notable toxicity was the allergenicity to be expected from infusing plasma products, usually manifesting as urticaria. Thus, results do not rule out the potential usefulness of passive immunization with different preparations, but did fail to demonstrate clinical benefit of the product studied. C1 MT SINAI MED CTR,NEW YORK,NY 10029. NEW YORK BLOOD CTR,NEW YORK,NY 10021. NICHHD,BETHESDA,MD 20892. RP JACOBSON, JM (reprint author), VET ADM MED CTR,INFECT DIS SECT,130 W KINGSBRIDGE RD,BRONX,NY 10468, USA. NR 39 TC 55 Z9 55 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 AUG PY 1993 VL 168 IS 2 BP 298 EP 305 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA LN813 UT WOS:A1993LN81300006 PM 8101550 ER PT J AU ELDAHER, N KEEFER, MC REICHMAN, RC DOLIN, R ROBERTS, NJ AF ELDAHER, N KEEFER, MC REICHMAN, RC DOLIN, R ROBERTS, NJ TI PERSISTING HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GP160-SPECIFIC HUMAN T-LYMPHOCYTE RESPONSES INCLUDING CD8+ CYTOTOXIC ACTIVITY AFTER RECEIPT OF ENVELOPE VACCINES SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HERPES-SIMPLEX VIRUS; MONONUCLEAR LEUKOCYTES; INTERFERON-PRODUCTION; RECOMBINANT GP160; HIV-1; CELLS; PROTECTION; CD4+; CHIMPANZEES; VACCINATION AB Mononuclear leukocytes (MNL) were obtained from vaccinia-naive, non-human immunodeficiency virus (HIV) infected subjects who were vaccinated with HIV-1-derived recombinant (r) live vaccinia-gp160, 4 of whom were boosted 1-2 years later with purified rgp160. MNL obtained after receipt of the vaccinia-gp160 alone showed persisting (greater-than-or-equal-to 1 year) gp160-specific lymphocyte proliferative responses and production of immune-specific interferon (IFN)-gamma. All 4 subjects who were boosted with rgp160 responded to the boost, including 2 whose cellular responses had waned prior to the boost. MNL from these 4 exhibited gp160-specific proliferative responses, IFN-gamma production, and cytotoxic T lymphocyte activity. The gp160-specific cytolysis was severely reduced or abolished by depletion of CD8+ cells and was not detected using HLA class I-mismatched target cells. Persisting (greater-than-or-equal-to 15 months after boost) HIV gp160-specific T cell recognition and functional responses can be induced by HIV-derived envelope vaccines. C1 UNIV ROCHESTER,SCH MED,DEPT MED,INFECT DIS UNIT,BOX 689,ROCHESTER,NY 14642. NIAID,AIDS CLIN VACCINE TRIALS NETWORK,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-27658] NR 43 TC 39 Z9 39 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 AUG PY 1993 VL 168 IS 2 BP 306 EP 313 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA LN813 UT WOS:A1993LN81300007 PM 8335968 ER PT J AU TSAREV, SA TSAREVA, TS EMERSON, SU KAPIKIAN, AZ TICEHURST, J LONDON, W PURCELL, RH AF TSAREV, SA TSAREVA, TS EMERSON, SU KAPIKIAN, AZ TICEHURST, J LONDON, W PURCELL, RH TI ELISA FOR ANTIBODY TO HEPATITIS-E VIRUS (HEV) BASED ON COMPLETE OPEN-READING FRAME-2 PROTEIN EXPRESSED IN INSECT CELLS - IDENTIFICATION OF HEV INFECTION IN PRIMATES SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID NON-B HEPATITIS; TRANSMITTED NON-A; LINKED-IMMUNOSORBENT-ASSAY; MONOCLONAL-ANTIBODIES; FELINE CALICIVIRUS; C VIRUS; GENE; CHIMPANZEES; SEQUENCE; EPIDEMIC AB A recombinant baculovirus containing the complete open-reading frame (ORF)-2 region of the hepatitis E virus (HEV) genome was constructed. The major protein synthesized in insect cells infected with recombinant virus was about the size expected for the complete ORF-2 product. This protein reacted in a Western blot assay with plasma from an HEV-infected chimpanzee. Lysates of the recombinant virus-infected insect cells were used in ELISA to monitor seroconversion of eight primate species (chimpanzees, four species of Old World monkeys, and three species of New World monkeys) inoculated with HEV. Homologous detector anti-immunoglobulin was more sensitive than heterologous anti-immunoglobulin for detecting anti-HEV by ELISA. All primate species except tamarins seroconverted after inoculation with HEV, although anti-HEV titers of Old World monkey species were generally higher than those of New World monkey species. The ELISA with complete ORF-2 antigen appeared to be a sensitive and practical method for detecting anti-HEV. C1 NIAID,EPIDEMIOL SECT,INFECT DIS LAB,BETHESDA,MD 20892. GEORGETOWN UNIV,DIV MOLEC VIROL & IMMUNOL,ROCKVILLE,MD. WALTER REED ARMY INST RES,DEPT VIRAL DIS,DIV COMMUNICABLE DIS & IMMUNOL,WASHINGTON,DC 20307. RP TSAREV, SA (reprint author), NIAID,HEPATITUS VIRUSES SECT,INFECT DIS LAB,BLDG 7,RM 200,BETHESDA,MD 20892, USA. RI Ticehurst, John/I-7532-2012 FU NIAID NIH HHS [AI-05069] NR 33 TC 171 Z9 185 U1 1 U2 5 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 AUG PY 1993 VL 168 IS 2 BP 369 EP 378 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA LN813 UT WOS:A1993LN81300017 PM 8335973 ER PT J AU BYRNE, GI STEPHENS, RS ADA, G CALDWELL, HD SU, H MORRISON, RP VANDERPOL, B BAVOIL, P BOBO, L EVERSON, S HO, Y HSIA, RC KENNEDY, K KUO, CC MONTGOMERY, PC PETERSON, E SWANSON, A WHITAKER, C WHITTUMHUDSON, J YANG, CL ZHANG, YX ZHONG, GM AF BYRNE, GI STEPHENS, RS ADA, G CALDWELL, HD SU, H MORRISON, RP VANDERPOL, B BAVOIL, P BOBO, L EVERSON, S HO, Y HSIA, RC KENNEDY, K KUO, CC MONTGOMERY, PC PETERSON, E SWANSON, A WHITAKER, C WHITTUMHUDSON, J YANG, CL ZHANG, YX ZHONG, GM TI WORKSHOP ON IN-VITRO NEUTRALIZATION OF CHLAMYDIA-TRACHOMATIS - SUMMARY OF PROCEEDINGS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID OUTER-MEMBRANE PROTEIN; MONOCLONAL-ANTIBODIES; CELL-CULTURE; INFECTIVITY; EPITOPES AB A task force evaluated an in vitro antibody-mediated chlamydial neutralization assay for its utility as a method to assess functional correlates of antibody responses to Chlamydia trachomatis. Two monoclonal antibodies that recognize different major outer membrane protein (MOMP) epitopes for a C. trachomatis serovar B strain exhibit good in vitro neutralizing activity, with a maximum of 90% neutralization. Calculations based on the 50% neutralization point indicated that 100% neutralization could theoretically be achieved when only 10% of the MOMP molecules bound antibody. Monoclonal antibodies that recognized either a heterologous MOMP or the genus-specific chlamydial lipopolysaccharide did not produce neutralizing activity. The standardized assay will be useful to establish if in vitro neutralizing antibody responses are predictive of protective immunity and will aid in defining chlamydial antigens and epitopes that may be attractive vaccine candidates. C1 UNIV CALIF SAN FRANCISCO,DEPT LAB MED,SAN FRANCISCO,CA 94143. AUSTRALIAN NATL UNIV,JOHN CURTIN SCH MED RES,CANBERRA,ACT 2601,AUSTRALIA. NIAID,ROCKY MT LAB,HAMILTON,MT 59840. INDIANA UNIV,SCH MED,DEPT MED,INDIANAPOLIS,IN 46202. UNIV ROCHESTER,SCH MED,DEPT MICROBIOL & IMMUNOL,ROCHESTER,NY 14627. JOHNS HOPKINS UNIV,SCH MED,DEPT OPHTHALMOL,BALTIMORE,MD 21205. SOUTHAMPTON GEN HOSP,DEPT MICROBIOL,SOUTHAMPTON SO9 4XY,HANTS,ENGLAND. BOSTON UNIV,SCH MED,MAXWELL FINLAND LAB,BOSTON,MA 02118. UNIV WASHINGTON,SCH PUBL HLTH & COMMUNITY MED,DEPT PATHOBIOL,SEATTLE,WA 98195. WAYNE STATE UNIV,DEPT IMMUNOL & MICROBIOL,DETROIT,MI 48202. UNIV CALIF IRVINE,DEPT MICROBIOL,IRVINE,CA 92717. UNIV WINNIPEG,DEPT MICROBIOL,WINNIPEG R3B 2E9,MANITOBA,CANADA. RP BYRNE, GI (reprint author), UNIV WISCONSIN,DEPT MED MICROBIOL & IMMUNOL,1300 UNIV AVE,MADISON,WI 53706, USA. FU NIAID NIH HHS [R01 AI019782] NR 21 TC 48 Z9 48 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG PY 1993 VL 168 IS 2 BP 415 EP 420 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA LN813 UT WOS:A1993LN81300023 PM 8335979 ER PT J AU JACOBSON, MA CAUSEY, D POLSKY, B HARDY, D CHOWN, M DAVIS, R ODONNELL, JJ KUPPERMANN, BD HEINEMANN, MH HOLLAND, GN MILLS, J FEINBERG, JE AF JACOBSON, MA CAUSEY, D POLSKY, B HARDY, D CHOWN, M DAVIS, R ODONNELL, JJ KUPPERMANN, BD HEINEMANN, MH HOLLAND, GN MILLS, J FEINBERG, JE TI A DOSE-RANGING STUDY OF DAILY MAINTENANCE INTRAVENOUS FOSCARNET THERAPY FOR CYTOMEGALOVIRUS RETINITIS IN AIDS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID ACQUIRED IMMUNODEFICIENCY SYNDROME; VIRUS RETINITIS; INFECTION AB Thirty-two patients with AIDS and previously untreated cytomegalovirus retinitis completed an induction course of foscarnet, 60 mg/kg every 8 h for 14 days, had retinitis stabilize, and were then randomly assigned to receive foscarnet maintenance as either a 90- or 120-mg/kg/day infusion administered over 2 h. Median survival was 157 and 336 days for the 90- and 120-mg/kg/day groups, respectively (P < .001). In an independent, masked analysis of retinal photographs, median time to progression of retinitis was 31 versus 95 days (P = .13). Daily intravenous foscarnet at a dose of 120 mg/kg (adjusted for renal function) resulted in significantly longer survival and tended to increase time to retinitis progression compared to the standard 90-mg/kg/day maintenance dose. Although a substantial increase in the risk of serious toxicity at the 120-mg/kg/day dose was not observed, the small sample size in this trial limited the power to detect differences that might be clinically important. C1 UNIV CALIF SAN FRANCISCO, DEPT MED, SAN FRANCISCO, CA 94143 USA. UNIV CALIF SAN FRANCISCO, DEPT OPHTHALMOL, SAN FRANCISCO, CA 94143 USA. UNIV SO CALIF, LOS ANGELES CTY MED CTR, DEPT MED, LOS ANGELES, CA 90033 USA. UNIV SO CALIF, LOS ANGELES CTY MED CTR, DEPT OPHTHALMOL, LOS ANGELES, CA 90033 USA. UNIV CALIF LOS ANGELES, CTR HLTH SCI, JULES STEIN EYE INST, CTR OCULAR INFLAMMATORY DIS, LOS ANGELES, CA USA. UNIV CALIF LOS ANGELES, CTR HLTH SCI, JULES STEIN EYE INST, DEPT MED, LOS ANGELES, CA USA. UNIV CALIF LOS ANGELES, CTR HLTH SCI, JULES STEIN EYE INST, DEPT OPHTHALMOL, LOS ANGELES, CA USA. MEM SLOAN KETTERING CANC CTR, INFECT DIS SERV, NEW YORK, NY 10021 USA. MEM SLOAN KETTERING CANC CTR, OPHTHALMOL SERV, NEW YORK, NY 10021 USA. MEM SLOAN KETTERING CANC CTR, SURG SERV, NEW YORK, NY 10021 USA. CORNELL UNIV, MED CTR, COLL MED, NEW YORK, NY 10021 USA. HARVARD UNIV, SCH PUBL HLTH, DEPT BIOSTAT, BOSTON, MA 02115 USA. NIAID, DIV AIDS, AIDS CLIN TRIALS GRP, BETHESDA, MD 20892 USA. RP JACOBSON, MA (reprint author), SAN FRANCISCO GEN HOSP, MED & OPHTHALMOL SERV,AIDS PROGRAM,BLDG 80,WARD 84, 995 POTRERO AVE, SAN FRANCISCO, CA 94110 USA. NR 15 TC 52 Z9 52 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG PY 1993 VL 168 IS 2 BP 444 EP 448 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA LN813 UT WOS:A1993LN81300027 PM 8393058 ER PT J AU VISCIDI, RP BOBO, L HOOK, EW QUINN, TC AF VISCIDI, RP BOBO, L HOOK, EW QUINN, TC TI TRANSMISSION OF CHLAMYDIA-TRACHOMATIS AMONG SEX PARTNERS ASSESSED BY POLYMERASE CHAIN-REACTION SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID INFECTION AB The prevalence of Chlamydia infection in 95 sex partners was determined by both polymerase chain reaction (PCR) and cell culture. Thirty-three (18%) of 186 specimens were positive by culture and 61 (33%) were positive by PCR-EIA. PCR was positive in 75% (21/28) of male partners of PCR-positive women compared with culture, which was positive in only 45% (9/19) of male partners of culture-positive women (P = .053). For female partners of infected men, the difference was less marked. PCR was positive in 58% (21/36) of female partners of infected men versus culture, which was positive in 56% (15/36) of female partners of culture-positive men. The correlation of PCR between partners and sequence analysis of Chlamydia DNA showing the same sequence from sex partners of 7 couples support the accuracy of the assay. These data suggest that PCR is more sensitive than culture for detection of Chlamydia trachomatis, particularly for male partners of infected women. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV INFECT DIS,BALTIMORE,MD 21205. NIAID,BALTIMORE CITY HLTH DEPT,BETHESDA,MD 20892. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RP VISCIDI, RP (reprint author), JOHNS HOPKINS UNIV HOSP,SCH MED,DEPT PEDIAT,EUDOWOOD DIV INFECT DIS,BLALOCK BLDG,ROOM 1111,BALTIMORE,MD 21205, USA. FU NIAID NIH HHS [AI-30420, AI-6959] NR 13 TC 34 Z9 34 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 AUG PY 1993 VL 168 IS 2 BP 488 EP 492 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA LN813 UT WOS:A1993LN81300039 PM 8335993 ER PT J AU GILLITZER, R WOLFF, K TONG, D MULLER, C YOSHIMURA, T HARTMANN, AA STINGL, G BERGER, R AF GILLITZER, R WOLFF, K TONG, D MULLER, C YOSHIMURA, T HARTMANN, AA STINGL, G BERGER, R TI MCP-1 MESSENGER-RNA EXPRESSION IN BASAL KERATINOCYTES OF PSORIATIC LESIONS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE IN-SITU HYBRIDIZATION; MONOCYTE-MACROPHAGE CHEMOTAXIS ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; NECROSIS FACTOR-ALPHA; GROWTH-FACTOR; ENDOTHELIAL-CELLS; HUMAN-FIBROBLASTS; INTERFERON-GAMMA; LYMPHOCYTES-T; GENE JE; SKIN; PURIFICATION AB In addition to hyperproliferation of keratinocytes, psoriasis is characterized by pronounced leukocytic infiltration. In contrast to the epidermal localization of neutrophils and T lymphocytes, macrophages are almost exclusively restricted to the dermal compartment. By immunohistologic analysis, these dermal macrophages were mainly encountered in the papillary dermis and arranged along the rete ridges in close proximity to proliferating keratinocytes. Monocyte chemoattractant protein (MCP-1) anti-sense RNA probes yielded abundant signals over the proliferating basal keratinocytes of the tips of the rete ridges, and, to a lesser extent, in cells in the papillae. Thus, the strongest MCP-1 message in psoriatic lesions is found above the dermal-epidermal junction and this may explain the characteristic sub-basal distribution of dermal macrophages. These results suggest that MCP-1 is important in regulating the interaction between proliferating keratinocytes and dermal macrophages in psoriasis pathogenesis. C1 UNIV VIENNA,SCH MED,DEPT DERMATOL 1,A-1010 VIENNA,AUSTRIA. UNIV BERN,SCH MED,DEPT PATHOL,CH-3000 BERN,SWITZERLAND. NCI,FREDERICK CANC RES DEV CTR,BETHESDA,MD 20892. RP GILLITZER, R (reprint author), UNIV WURZBURG,SCH MED,DEPT DERMATOL,JOSEF SCHNEIDER STR 2,W-8700 WURZBURG,GERMANY. NR 40 TC 107 Z9 111 U1 1 U2 3 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 AUG PY 1993 VL 101 IS 2 BP 127 EP 131 DI 10.1111/1523-1747.ep12363613 PG 5 WC Dermatology SC Dermatology GA LP487 UT WOS:A1993LP48700004 PM 8345212 ER PT J AU ELGART, GW STANLEY, JR AF ELGART, GW STANLEY, JR TI CLONING OF THE 5' MESSENGER-RNA FOR THE 230-KD BULLOUS PEMPHIGOID ANTIGEN BY RAPID AMPLIFICATION OF CDNA ENDS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Note DE HEMIDESMOSOME; DESMOPLAKIN; ADHESION ID DESMOPLAKIN; PROTEIN; FAMILY; PLAQUE AB The 230-kD bullous pemphigoid antigen (BPAG1), defined by autoantibodies in patient sera, is a hemidesmosomal plaque protein in the same gene family as the intracellular proteins desmoplakin I/II and plectin. We had previously isolated, from a lambdagt11 library, overlapping cDNA clones with 6921 bp of mRNA sequence for BPAG1. The coding sequence encoded by these clones included the 3' stop codon but not the 5' coding and non-coding region of the mRNA. To obtain these sequences we used the polymerase chain reaction (PCR) method called rapid amplification of cDNA ends (PACE). The PCR products were cloned into plasmids and sequenced. With five PCR primers we were able to obtain overlapping clones containing the 5' region of the mRNA. An upstream stop codon in frame with the rest of the coding sequence demonstrates that the full 5' coding sequence is obtained. Four different PCR products from two separate reactions had the same 5' end, suggesting that this 5' end is near, or at, the transcription start site. No alternatively spliced clones were found and no transmembrane site was predicted, confirming that BPAG1 is an intracellular hemidesmosomal plaque protein. C1 NIH,DERMATOL BRANCH,BLDG 10,ROOM 12N238,BETHESDA,MD 20892. NR 11 TC 4 Z9 5 U1 0 U2 1 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 AUG PY 1993 VL 101 IS 2 BP 244 EP 246 DI 10.1111/1523-1747.ep12365083 PG 3 WC Dermatology SC Dermatology GA LP487 UT WOS:A1993LP48700027 PM 8345227 ER PT J AU DICHEK, HL PARROTT, C RONAN, R BRUNZELL, JD BREWER, HB SANTAMARINAFOJO, S AF DICHEK, HL PARROTT, C RONAN, R BRUNZELL, JD BREWER, HB SANTAMARINAFOJO, S TI FUNCTIONAL-CHARACTERIZATION OF A CHIMERIC LIPASE GENETICALLY-ENGINEERED FROM HUMAN LIPOPROTEIN-LIPASE AND HUMAN HEPATIC LIPASE SO JOURNAL OF LIPID RESEARCH LA English DT Article DE APOLIPOPROTEIN C-II; CHIMERA MESSENGER RNA; CHIMERA CDNA; HEPARIN BINDING PROPERTIES ID SITE-DIRECTED MUTAGENESIS; TRIGLYCERIDE LIPASE; POSTHEPARIN PLASMA; PANCREATIC LIPASE; BOVINE-MILK; GUINEA-PIG; GENE; SEQUENCE; ENZYME; IDENTIFICATION AB Lipoprotein lipase (LPL) and hepatic lipase (HL) mediate the hydrolysis of triglycerides and phospholipids present in circulating lipoprotein particles and are essential for normal lipid metabolism. Both enzymes have a similar primary amino acid structure and share requirements for intact catalytic, lipid binding, and heparin binding domains. However, LPL and HL exhibit different substrate specificities and cofactor requirements. In order to characterize the functional domains necessary for LPL activity, a chimeric lipase consisting of the amino-terminal 314 amino acids of human LPL and the carboxyl-terminal 146 amino acids of human HL was synthesized by joining the cDNA of both lipases at the 5'-end of exon 7. Northern blot hybridization and Western blot analyses revealed the size of the chimera mRNA and protein to be approximately 1.5 kb and 55 kDa, respectively. The chimeric enzyme hydrolyzed both long chain and short chain fatty acid triacylglycerols and had catalytic properties that were similar to lipoprotein lipase. Thus, apolipoprotein (apo)C-II was required for maximal lipase activity, and high salt concentration abolished the ability of the chimera to hydrolyze triolein even in the presence of apoC-II. A monospecific anti-HL polyclonal antibody interacting with the C-terminal HL-derived domain of the chimeric enzyme abolished the enzyme's ability to hydrolyze triglyceride emulsion but not tributyrin substrates. Analysis of the heparin binding properties of the chimeric enzyme using heparin-Sepharose affinity chromatography revealed an elution pattern which was intermediate between that of lipoprotein and hepatic lipase. In summary, we have characterized the functional properties of an LPL-HL chimeric enzyme. Our studies indicate that the LPL-derived NH2-terminal domain is the site of interaction between apoC-II and LPL and determines the catalytic properties of the chimera, whereas the HL-derived C-terminal domain plays a major role in mediating the lipase interaction with long chain triacylglycerol substrates. In addition, both the LPL-derived NH2-terminal domain and the HL-derived C-terminal domain contribute to the heparin binding properties of the LPL-chimera. C1 UNIV WASHINGTON,DEPT MED,DIV METAB ENDOCRINOL & NUTR,SEATTLE,WA 98195. RP DICHEK, HL (reprint author), NHLBI,MOLEC DIS BRANCH,BLDG 10-7N117,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NIDDK NIH HHS [DK-02456] NR 44 TC 47 Z9 47 U1 0 U2 0 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 AUG PY 1993 VL 34 IS 8 BP 1393 EP 1401 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LQ598 UT WOS:A1993LQ59800012 PM 8409770 ER PT J AU GRZESIEK, S BAX, A AF GRZESIEK, S BAX, A TI THE ORIGIN AND REMOVAL OF ARTIFACTS IN 3D HCACO SPECTRA OF PROTEINS UNIFORMLY ENRICHED WITH C-13 SO JOURNAL OF MAGNETIC RESONANCE SERIES B LA English DT Note ID TRIPLE-RESONANCE NMR; LARGER PROTEINS; SPECTROSCOPY; ASSIGNMENT; PHASE; H-1; 2D RP GRZESIEK, S (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. NR 14 TC 49 Z9 50 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 1064-1866 J9 J MAGN RESON SER B JI J. Magn. Reson. Ser. B PD AUG PY 1993 VL 102 IS 1 BP 103 EP 106 DI 10.1006/jmrb.1993.1069 PG 4 WC Physics, Atomic, Molecular & Chemical SC Physics GA LT933 UT WOS:A1993LT93300015 ER PT J AU BOURG, J KRISHNA, MC MITCHELL, JB TSCHUDIN, RG POHIDA, TJ FRIAUF, WS SMITH, PD METCALFE, J HARRINGTON, F SUBRAMANIAN, S AF BOURG, J KRISHNA, MC MITCHELL, JB TSCHUDIN, RG POHIDA, TJ FRIAUF, WS SMITH, PD METCALFE, J HARRINGTON, F SUBRAMANIAN, S TI RADIOFREQUENCY FT EPR SPECTROSCOPY AND IMAGING SO JOURNAL OF MAGNETIC RESONANCE SERIES B LA English DT Note ID SPECTROMETER C1 NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,RADIAT ONCOL BRANCH,RADIAT BIOL SECT,BETHESDA,MD 20892. NIDDKD,CHEM PHYS LAB,DIV NMR,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NR 10 TC 35 Z9 35 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 1064-1866 J9 J MAGN RESON SER B JI J. Magn. Reson. Ser. B PD AUG PY 1993 VL 102 IS 1 BP 112 EP 115 DI 10.1006/jmrb.1993.1071 PG 4 WC Physics, Atomic, Molecular & Chemical SC Physics GA LT933 UT WOS:A1993LT93300017 ER PT J AU RIMOLDI, JM KINGSTON, DGI CHAUDHARY, AG SAMARANAYAKE, G GROVER, S HAMEL, E AF RIMOLDI, JM KINGSTON, DGI CHAUDHARY, AG SAMARANAYAKE, G GROVER, S HAMEL, E TI MODIFIED TAXOLS .9. SYNTHESIS AND BIOLOGICAL EVALUATION OF 7-SUBSTITUTED PHOTOAFFINITY ANALOGS OF TAXOL SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID MICROTUBULE-ASSOCIATED PROTEINS; ISOPENICILLIN-N SYNTHETASE; TUBULIN POLYMERIZATION; BETA-TUBULIN; LOCALIZATION; MECHANISM; AGENT; COLCHICINE; PHOTOLYSIS; SEPARATION AB The 7-substituted taxol analogues 7, 19, 27, and 32 have been prepared as potential photoaffinity-labeled derivatives for studies of the nature of the binding site of taxol on polymerized tubulin. The analogue 32 has been prepared in both deuterium- and tritium-labeled versions. Tubulin-assembly studies were carried out with these compounds, and it was found that they showed some but not all of the properties of taxol. We conclude that these specific taxol analogues labeled at the 7 position are not ideal derivatives for photoaffinity labeling studies. C1 VIRGINIA POLYTECH INST & STATE UNIV,DEPT CHEM,BLACKSBURG,VA 24061. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA48974] NR 47 TC 33 Z9 34 U1 0 U2 2 PU AMER SOC PHARMACOGNOSY PI CINCINNATI PA LLOYD LIBRARY & MUSEUM 917 PLUM ST, CINCINNATI, OH 45202 SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD AUG PY 1993 VL 56 IS 8 BP 1313 EP 1330 DI 10.1021/np50098a016 PG 18 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA LW182 UT WOS:A1993LW18200016 PM 7901340 ER PT J AU FIELDS, RD GUTHRIE, PB RUSSELL, JT KATER, SB MALHOTRA, BS NELSON, PG AF FIELDS, RD GUTHRIE, PB RUSSELL, JT KATER, SB MALHOTRA, BS NELSON, PG TI ACCOMMODATION OF MOUSE DRG GROWTH CONES TO ELECTRICALLY-INDUCED COLLAPSE - KINETIC-ANALYSIS OF CALCIUM TRANSIENTS AND SET-POINT THEORY SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE GROWTH CONE COLLAPSE; CALCIUM HOMEOSTASIS; ACTIVITY-DEPENDENT PLASTICITY; DEVELOPMENT; MOTILITY; FURA-2; REGENERATION ID NEURITE OUTGROWTH; SENSORY NEURONS; INTRACELLULAR CALCIUM; DENDRITIC SPINES; CELLS; CA-2+; ELONGATION; CHANNELS; DEPOLARIZATION; HOMEOSTASIS AB Electrical stimulation causes growth cones of mouse dorsal root ganglion neurons to collapse. During chronic stimulation, however, growth cones resume motility. In addition, these growth cones are now resistant to the collapsing effects of subsequent stimulation, a process we term accommodation. We compared the kinetics of electrically induced Ca2+ transients in naive and accommodated growth cones in order to determine whether the accommodation process results from a change in the Ca2+ transient, or a change in the Ca2+ sensitivity of the growth cones. Three kinetics were determined: (I ) the initial increase to peak Ca2+ levels produced by 10 Hz stimulation; (2) recovery from peak Ca2+ levels during stimulus trains lasting 15 min; and (3) clearing of Ca2+ from growth cones after terminating the stimulus. These kinetics were analyzed using single exponential fits to changes in fura-2 fluorescence ratios. The electrically evoked increase in Ca2+ was significantly slower in accommodated growth cones (tau = 6.0 s) compared to naive growth cones (tau = 1.4 s). Despite the slower increase of [Ca2+]i in accommodated growth cones, peak [Ca2+]i was similar to that reached in naive growth cones, and the steady-state Ca2+ level was significantly elevated after chronic stimulation. Thus, accommodated growth cones maintained outgrowth at [Ca2+]i that caused collapse initially. Time course experiments show that accommodation is a slow process (t1/2 = about 3 h). Accommodation did not induce measurable changes in the rates of Ca2+ homeostasis during or after stimulus trains. The kinetics of Ca2+ recovery during (tau = 90 s) and after 15 min of stimulation (tau = 8.5 s) was not significantly different in accommodated versus naive growth cones. Rates of (Ca2+)-Ca-45 efflux were also similar in both types of growth cones. These results suggest two regulatory processes contributing to growth cone motility during chronic stimulation: (1) recovery of [Ca2+]- to levels permissive to neurite outgrowth, and (2) an increase in the range of optimal [Ca2+]i for growth cone motility. These adaptive responses of mammalian growth cones to chronic stimulation could be involved in the modulation of CNS development by electrical activity of neurons. (C) 1993 John Wiley * Sons, Inc. C1 COLORADO STATE UNIV,DEPT ANAT,FT COLLINS,CO 80523. RP FIELDS, RD (reprint author), NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD 20892, USA. NR 41 TC 57 Z9 57 U1 1 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD AUG PY 1993 VL 24 IS 8 BP 1080 EP 1098 DI 10.1002/neu.480240807 PG 19 WC Neurosciences SC Neurosciences & Neurology GA LN610 UT WOS:A1993LN61000006 PM 8409969 ER PT J AU YU, OF CHUANG, DM AF YU, OF CHUANG, DM TI LONG-TERM GABA TREATMENT ELICITS SUPERSENSITIVITY OF QUISQUALATE-PREFERRING METABOTROPIC GLUTAMATE-RECEPTOR IN CULTURED RAT CEREBELLAR NEURONS SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE GABA RECEPTORS; METABOTROPIC GLUTAMATE RECEPTORS; TOLERANCE; DEPENDENCE; WITHDRAWAL SUPERSENSITIVITY; PHOSPHOINOSITIDE HYDROLYSIS ID EXCITATORY AMINO-ACIDS; GRANULE CELLS; NEOCORTICAL NEURONS; MODULATION; RELEASE; PHARMACOLOGY; WITHDRAWAL; RESPONSES; AGONIST AB In primary cultures of rat cerebellar granule neurons, GABA treatment (50 muM, 7 days) caused a withdrawal supersensitivity selective for the metabotropic glutamate receptors that mainly prefer L-glutamate, quisqualate and, to a lesser extent, kainate. The withdrawal supersensitivity was absent when 10 muM SR-95531 was coadministered with GABA during the treatment period, an event that suggests the GABA(A) receptors primarily produced the GABA treatment effect. This was supported further by the inability of baclofen treatment to mimic completely the treatment effect of GABA. Withdrawal from 7 days of baclofen treatment only produced a slight increase in the metabotropic effect Of L-glutamate and carbachol. In addition, in untreated neurons, baclofen had no acute effect, whereas GABA inhibited the effect Of L-glutamate and carbachol. The inhibitory effect of GABA was reversed by SR-95531 and was absent in neurons treated with GABA. These observations suggest the involvement of GABA(A) receptors and the apparent development of tolerance to GABA, respectively. Also, dependence on GABA may have occurred; the metabotropic effects of glutamate, kainate, and quisqualate were not altered in neurons maintained with GABA treatment. C1 NIMH,BIOL PSYCHIAT BRANCH,MOLEC NEUROBIOL SECT,BLDG 10,ROOM 3N212,BETHESDA,MD 20892. NR 29 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 1993 VL 61 IS 2 BP 430 EP 435 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA LM753 UT WOS:A1993LM75300003 PM 8101556 ER PT J AU PATEL, A UHL, G KUHAR, MJ AF PATEL, A UHL, G KUHAR, MJ TI SPECIES-DIFFERENCES IN DOPAMINE TRANSPORTERS - POSTMORTEM CHANGES AND GLYCOSYLATION DIFFERENCES SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE DOPAMINE; TRANSPORTER; SPECIES; GLYCOSYLATION; PHOTOAFFINITY; POSTMORTEM DELAY ID NUCLEUS-ACCUMBENS; CAUDATE-NUCLEUS; RAT STRIATUM; CLONING; SYNAPTOSOMES; EXPRESSION; CDNA; TEMPERATURE; PROTEIN; BINDING AB The apparent molecular masses of photoaffinity-labeled dopamine transporters (DATs) from rat, human, dog, and primate kidney COS cells expressing the rat DAT1 cDNA differ. Sequences predicted from cDNA cloning reveal only one amino acid difference between the length of the rat and human DAT but one less site for potential N-linked glycosylation in the human DAT. Possible posttranslational and postmortem bases for species differences in DAT molecular mass were explored. Rat DAT proteins from striata subjected to approximately 5 h of postmortem delay modeled after the human postmortem delay process revealed small but consistent losses in apparent molecular mass and in cocaine analogue binding; the DAT molecular mass displayed no further losses for up to 30 h of model postmortem treatment. Degradative postmortem changes could thus contribute to molecular mass differences between rat and human DATs. Neuraminidase treatment reduced the apparent molecular mass of native rat DAT but not that of the rat DAT expressed in COS cells, suggesting that the sugars added to the DAT expressed in COS cells were different than those added to the rat brain striatal transporter. These differences could account for the somewhat higher K(m) values for expressed DAT cDNA in COS cells when compared with the wild-type striatal transporter. These results are in accord with the differences in number of predicted N-linked glycosylation sites between rat and human DATs and with cell-type specificity in transporter posttranslational processing. C1 NIDA,ADDICT RES CTR,NEUROSCI BRANCH,MOLEC PHARMACOL SECT,POB 5180,BALTIMORE,MD 21224. NIDA,ADDICTION RES CTR,NEUROSCI BRANCH,MOLEC NEUROBIOL SECT,BALTIMORE,MD 21224. NR 24 TC 52 Z9 52 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 1993 VL 61 IS 2 BP 496 EP 500 PG 5 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA LM753 UT WOS:A1993LM75300012 PM 8336137 ER PT J AU RABIN, O HEGEDUS, L BOURRE, JM SMITH, QR AF RABIN, O HEGEDUS, L BOURRE, JM SMITH, QR TI RAPID BRAIN UPTAKE OF MANGANESE(II) ACROSS THE BLOOD-BRAIN-BARRIER SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE BLOOD BRAIN BARRIER; MANGANESE; PLASMA PROTEIN BINDING; TRANSPORT; NEUROTOXICITY; PARKINSONS DISEASE ID CHOROID-PLEXUS; TRANSFERRIN RECEPTOR; CEREBROSPINAL-FLUID; TRACE-ELEMENTS; RAT; TRANSPORT; PLASMA; CALCIUM; NEUROTOXICITY; CAPILLARIES AB Mn-54(2+) uptake into brain and choroid plexus from the circulation was studied using the in situ rat brain perfusion technique. Initial uptake from blood was linear with time (30 s to 6 min) and extrapolated to zero with an average transfer coefficient of approximately 6 x 10(-5) ml/s/g for brain and approximately 7 x 10(-3) ml/s/g for choroid plexus. Influx from physiologic saline was three- to fourfold more rapid and exceeded that predicted for passive diffusion by more than one order of magnitude. The lower uptake rate from blood could be explained by plasma protein binding as the free fraction of Mn-54(2+) in rat plasma was less-than-or-equal-to 30%. Purified albumin, transferrin, and alpha2-macroglobulin were each found to bind Mn-54(2+) significantly and to restrict brain Mn-54(2+) influx. The results demonstrate that Mn-54(2+) is readily taken up into the CNS, most likely as the free ion, and that transport is critically affected by plasma protein binding. The results support the hypothesis that Mn2+ transport across the blood-brain barrier is facilitated by either an active or a passive mechanism. C1 NIA,NEUROSCI LAB,BLDG 10,ROOM 6C103,BETHESDA,MD 20892. HOP FERNAND WIDAL,INSERM,U26,F-75475 PARIS 10,FRANCE. NR 47 TC 129 Z9 131 U1 0 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 1993 VL 61 IS 2 BP 509 EP 517 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA LM753 UT WOS:A1993LM75300014 PM 7687654 ER PT J AU SCHAPIRO, MB PIETRINI, P GRADY, CL BALL, MJ DECARLI, C KUMAR, A KAYE, JA HAXBY, JV AF SCHAPIRO, MB PIETRINI, P GRADY, CL BALL, MJ DECARLI, C KUMAR, A KAYE, JA HAXBY, JV TI REDUCTIONS IN PARIETAL AND TEMPORAL CEREBRAL METABOLIC RATES FOR GLUCOSE ARE NOT SPECIFIC FOR ALZHEIMERS-DISEASE SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; PARKINSONS-DISEASE; NUCLEUS BASALIS; DEMENTIA; PATTERNS; ASYMMETRIES; LESIONS; CORTEX AB Reduction in the regional cerebral metabolic rate for glucose (rCMRglc) in the parietal and temporal regions has been shown in Alzheimer's disease (AD). The specificity of these findings for this disease state is uncertain. We repeatedly measured rCMRglc with positron emission tomography and [18F]2-fluoro-2-deoxy-D-glucose in the resting state in a 68 year old man with slowly progressive dementia who, during life, was initially diagnosed as having dementia of the Alzheimer type, then Parkinson disease with dementia, but was found to have only Parkinson's disease at necropsy. Metabolic ratios (rCMRglc/mean grey CMRglc) were significantly (p < 0.05) reduced in parietal and temporal regions, as well as in the prefrontal and premotor areas. This pattern was similar in regional distribution and magnitude of the defect to that seen in patients with probable AD. These results suggest that reductions of glucose metabolism in association neocortex in AD are not specific to the disease process, but may be related to the dementia state. C1 UNIV WESTERN ONTARIO,DEPT PATHOL,ATKINSON NEUROBIOL AGING UNIT,DEMENTIA STUDY LAB,LONDON M6A 5C1,ON,CANADA. RP SCHAPIRO, MB (reprint author), NIA,CTR CLIN,NEUROSCI LAB,BRAIN AGING & DEMENTIA SECT,BLDG 10 RM 6C414,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI DeCarli, Charles/B-5541-2009; OI Kaye, Jeffrey/0000-0002-9971-3478 NR 31 TC 38 Z9 38 U1 1 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD AUG PY 1993 VL 56 IS 8 BP 859 EP 864 DI 10.1136/jnnp.56.8.859 PG 6 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA LQ938 UT WOS:A1993LQ93800004 PM 8350100 ER PT J AU MUNOZ, DP WURTZ, RH AF MUNOZ, DP WURTZ, RH TI FIXATION CELLS IN MONKEY SUPERIOR COLLICULUS .1. CHARACTERISTICS OF CELL DISCHARGE SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID PARIETAL ASSOCIATION CORTEX; PURSUIT EYE-MOVEMENTS; ORIENTING GAZE SHIFTS; CORTICAL AREAS MT; HEAD-FREE CAT; FUNCTIONAL-PROPERTIES; TECTORETICULOSPINAL SYSTEM; OCULOMOTOR FUNCTIONS; NEURONAL-ACTIVITY; VISUAL RESPONSES AB 1. We studied the role of the superior colliculus (SC) in the control of visual fixation by recording from cells in the rostral pole of the SC in awake monkeys that were trained to perform fixation and saccade tasks. 2. We identified a subset of neurons in three monkeys that we refer to as fixation cells. These cells increased their tonic discharge rate when the monkey actively fixated a visible target spot to obtain a reward. This sustained activity persisted when the visual stimulation of the target spot was momentarily removed but the monkey was required to continue fixation. 3. The fixation cells were in the rostral pole of the SC. As the electrode descended through the SC, we encountered visual cells with foveal and parafoveal receptive fields most superficially, saccade-related burst cells with parafoveal movement fields below these visual cells, and fixation cells below the burst cells. From this sequence in depth, the fixation cells appeared to be centered in the deeper reaches of the intermediate layers, and this was confirmed by small marking lesions identified histologically. 4. During saccades, the tonically active fixation cells showed a pause iii their rate of discharge. The duration of this pause was correlated to the duration of the saccade. Many cells did not decrease their discharge mte for small-amplitude contraversive saccades. 5. The saccade-related pause in fixation cell discharge always began before the onset of the saccade. The mean time from pause onset to saccade onset for contraversive saccades and ipsiversive saccades was 36.2 and 33.0 ms, respectively. Most fixation cells were reactivated before the end of contraversive saccades. The mean time from saccade termination to pause end was -2.6 ms for contraversive saccades and 9.9 ms for ipsiversive saccades. The end of the saccade-related pause in fixation cell discharge was more lightly correlated to saccade termination, than pause onset was to saccade onset. 6. After the saccade-related pause in discharge, many fixation cells showed an increased discharge rate exceeding that before the pause. This increased postsaccadic discharge rate persisted for several hundred milliseconds. 7. The discharge rate of fixation cells was not consistently altered when the monkey actively fixated targets requiring different orbital positions. 8. Fixation cells discharged during smooth pursuit eye movements as they did during fixation. They maintained a steady tonic discharge during pursuit at different speeds and in different directions, provided the monkey looked at the moving target. 9. We hypothesize that the fixation cells in the rostral pole of the monkey SC provide a signal related to active visual fixation. Activation of these cells would inhibit the activity of saccade-related cells in the rest of the SC and the saccade premotor circuitry in the brain stem. A prerequisite step in the generation of a saccade would be the reduction of activity in these collicular fixation cells. C1 NEI,SENSORIMOTOR RES LAB,BLDG 49,RM 2A50,BETHESDA,MD 20892. QUEENS UNIV,MRC,DEPT PHYSIOL,SENSORY MOTOR PHYSIOL GRP,KINGSTON K7L 3N6,ONTARIO,CANADA. NR 57 TC 463 Z9 465 U1 2 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD AUG PY 1993 VL 70 IS 2 BP 559 EP 575 PG 17 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA LU331 UT WOS:A1993LU33100010 PM 8410157 ER PT J AU MUNOZ, DP WURTZ, RH AF MUNOZ, DP WURTZ, RH TI FIXATION CELLS IN MONKEY SUPERIOR COLLICULUS .2. REVERSIBLE ACTIVATION AND DEACTIVATION SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID SACCADIC EYE-MOVEMENTS; ORIENTING GAZE SHIFTS; HEAD-FREE CAT; EXPRESS-SACCADES; REACTION-TIMES; OPTIC TRACT; TECTORETICULOSPINAL SYSTEM; NEURONS; NUCLEUS; DISCHARGES AB 1. We tested the hypothesis that a subset of neurons, which we have referred to as fixation cells, located within the rostral pole of the monkey superior colliculus (SC) controls the generation of saccadic eye movements. We altered the activity of these neurons with either electrical stimulation or GABAergic drugs. 2. An increase in the activity of fixation cells in the rostral SC, induced by a train of low-frequency electrical stimulation, delayed the initiation of saccades. With bilateral stimulation the monkey was able to make saccades only after stimulation ceased. 3. Pulses of stimulation delivered during the saccade produced an interruption of the saccade in midflight. The latency to the onset of this perturbation was as short as 12 ms. 4. Injection of the gamma-aminobutyric acid (GABA) antagonist bicuculline into the rostral pole of the SC, which decreases normal GABA inhibition and increases cell activity, increased the latency of saccades to both visual and remembered targets. 5. Injection of the GABA agonist muscimol into the rostral SC, which increases normal GABA inhibition and decreases activity, reduced the latency for saccades to visual targets. The monkey also had difficulty maintaining visual fixation and suppressing unwanted saccades. 6. After muscimol injections, monkeys frequently made very short-latency saccades forming a peak in the saccade latency histogram at < 100 ms. These saccades are similar to express saccades made by normal monkeys. This finding suggests that the fixation cells in the rostral SC are critical for controlling the frequency of express saccades. 7. These results support the hypothesis that fixation cells in the rostral SC inhibit the generation of saccadic eye movements and that they form part of a system of oculomotor control, that of visual fixation. C1 NEI,SENSORIMOTOR RES LAB,BLDG 49,RM 2A50,BETHESDA,MD 20892. QUEENS UNIV,MRC,DEPT PHYSIOL,SENSORY MOTOR PHYSIOL GRP,KINGSTON K7L 3N6,ONTARIO,CANADA. NR 27 TC 330 Z9 330 U1 2 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD AUG PY 1993 VL 70 IS 2 BP 576 EP 589 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA LU331 UT WOS:A1993LU33100011 PM 8410158 ER PT J AU PATNEAU, DK VYKLICKY, L MAYER, ML AF PATNEAU, DK VYKLICKY, L MAYER, ML TI HIPPOCAMPAL-NEURONS EXHIBIT CYCLOTHIAZIDE-SENSITIVE RAPIDLY DESENSITIZING RESPONSES TO KAINATE SO JOURNAL OF NEUROSCIENCE LA English DT Article DE KAINATE; AMPA; DESENSITIZATION; HIPPOCAMPUS; EXCITATORY AMINO ACIDS; CYCLOTHIAZIDE; GLUTAMATE; RECEPTOR; ALLOSTERIC REGULATION; CONCENTRATION JUMP ID GLUTAMATE RECEPTOR CHANNELS; AMINO-ACID RECEPTORS; NOOTROPIC DRUG ANIRACETAM; METHYL-D-ASPARTATE; QUISQUALATE RECEPTORS; ACTIVATED CHANNELS; ION CHANNELS; K+ CHANNELS; SUBUNIT; MODULATION AB In whole-cell recordings from mammalian CNS neurons, AMPA-preferring glutamate receptors exhibit strong desensitization in response to AMPA, glutamate, and quisqualate, but not to kainate or domoate. Such desensitization is reduced by lectins, by the nootropic drug aniracetam, and by diazoxide. None of these compounds strongly modulate responses to kainate and domoate, consistent with the apparent lack of desensitization to these agonists. We now report experiments on hippocampal neurons in which responses to kainate were strongly potentiated by cyclothiazide, a benzothiadiazine diuretic and antihypertensive drug structurally related to diazoxide. Cyclothiazide increased the maximum response to a saturating concentration of kainate by approximately 300% and produced a shift to the left in the kainate dose-response curve. Because cyclothiazide was considerably more effective than aniracetam in reducing desensitization evoked by glutamate, we tested the possibility that potentiation of responses to kainate was due to block of a previously undetected component of desensitization in the response to kainate itself. In outside-out patches responses to rapid perfusion of 3 mm kainate showed 34% desensitization, the onset of which developed with a time constant of 2.2 msec. Desensitization of responses to kainate was abolished by 100 mum cyclothiazide, as was the much stronger desensitization evoked by glutamate and AMPA. Cyclothiazide also slowed the rate of deactivation of responses to kainate recorded after return to agonist-free solution. Current-voltage plots for control responses to kainate exhibited outward rectification that was associated with a reduction in the amount of desensitization on depolarization. Both effects were absent in the presence of cyclothiazide, suggesting that rectification of responses to kainate was due to the voltage dependence of desensitization. The complete block of desensitization produced by cyclothiazide provides a powerful new tool for analysis of allosteric regulatory mechanisms at AMPA-preferring glutamate receptors. C1 NICHHD,CELLULAR & MOLEC NEUROPHYSIOL LAB,BLDG 49,ROOM 5A78,BETHESDA,MD 20892. CZECHOSLOVAK ACAD SCI,INST PHYSIOL,CS-14220 PRAGUE 4,CZECHOSLOVAKIA. RI Vyklicky, Ladislav/C-1851-2012; Mayer, Mark/H-5500-2013 OI Vyklicky, Ladislav/0000-0002-0015-0098; NR 50 TC 338 Z9 339 U1 3 U2 8 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 AUG PY 1993 VL 13 IS 8 BP 3496 EP 3509 PG 14 WC Neurosciences SC Neurosciences & Neurology GA LR779 UT WOS:A1993LR77900025 PM 7688040 ER PT J AU SHENG, HZ FIELDS, RD NELSON, PG AF SHENG, HZ FIELDS, RD NELSON, PG TI SPECIFIC REGULATION OF IMMEDIATE-EARLY GENES BY PATTERNED NEURONAL-ACTIVITY SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE IEG EXPRESSION; PATTERNED ACTIVITY; CALCIUM ID LONG-TERM POTENTIATION; C-FOS; MEMBRANE DEPOLARIZATION; GROWTH-FACTORS; MESSENGER-RNA; DENTATE GYRUS; ACTIVATION; INDUCTION; TRANSCRIPTION; CALCIUM AB Electrical activity shapes development of the nervous system, presumably in part by regulating gene expression. A set of regulatory genes, immediate early genes (IEGs), which are responsive to a number of extrinsic cellular stimuli have been proposed to play a role in coupling such activity to gene expression. Using a semiquantitative polymerase chain reaction assay, we show that in dissociated mouse dorsal root ganglion neurons the expression of two IEGs, c-fos and nur/77, is differentially sensitive to patterns of electrical stimulation. Differences in c-fos activation did not correlate with the peak intracellular calcium [Ca++]i produced by the different stimulation patterns or with residual [Ca++]i following stimulation. However, the net increase in [Ca++]i (calcium time integral) was greater for the pulsed stimulus that activated c-fos (6 impulses/min), compared to the ineffective stimulus (12 impulses/2 min). This system of genes seems suited to mediating the coupling between electrical activity and other functional genes. (C) 1993 Wiley-Liss, Inc.* RP SHENG, HZ (reprint author), NICHHD,DEV NEUROBIOL LAB,BLDG 49,ROOM 5A38,BETHESDA,MD 20892, USA. NR 26 TC 79 Z9 79 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD AUG 1 PY 1993 VL 35 IS 5 BP 459 EP 467 DI 10.1002/jnr.490350502 PG 9 WC Neurosciences SC Neurosciences & Neurology GA LN633 UT WOS:A1993LN63300001 PM 8377220 ER PT J AU HAMMER, JA OSHANNESSY, DJ DELEON, M GOULD, R ZAND, D DAUNE, G QUARLES, RH AF HAMMER, JA OSHANNESSY, DJ DELEON, M GOULD, R ZAND, D DAUNE, G QUARLES, RH TI IMMUNOREACTIVITY OF PMP-22, P0, AND OTHER 19 TO 28 KDA GLYCOPROTEINS IN PERIPHERAL-NERVE MYELIN OF MAMMALS AND FISH WITH HNK1 AND RELATED ANTIBODIES SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE ADHESION GLYCOPROTEINS; EVOLUTION OF MYELIN; NEUROPATHY WITH ANTI-MAG ANTIBODIES ID TOOTH DISEASE TYPE-1A; CELL-ADHESION MOLECULES; HUMAN MONOCLONAL-ANTIBODIES; ARREST-SPECIFIC GENE; RAT SCIATIC-NERVE; GROWTH ARREST; SYSTEM MYELIN; PO-PROTEIN; L2/HNK-1 CARBOHYDRATE; MAJOR GLYCOPROTEIN AB Mammalian peripheral nervous system (PNS) myelin contains several glycoproteins with molecular weights of 19 to 28 kDa, including the major 28 kDa P0 glycoprotein and a recently cloned protein called PMP-22. Some glycoproteins in this M(r) range in humans, cats and some other mammals react with HNK1, a mouse monoclonal antibody that identifies a carbohydrate epitope shared between the immune system and a number of adhesion proteins in the nervous system. A variety of antibodies to P0, PMP-22, and the carbohydrate determinants reacting with HNK1 were used to characterize immunochemically these 19 to 28 kDa glycoproteins of cat PNS myelin. The HNK1-reactive components include P0 and two slightly smaller 23 to 26 kDa proteins that are immunologically related to P0. However, HNK1 reacts most strongly with a lower molecular weight glycoprotein that does not react with the antibodies to P0 and was identified as PMP-22. Since the carbohydrate structure reacting with HNK1 is generally expressed on adhesion molecules, this result suggests that PMP-22 may function in cell-cell or membrane-membrane interactions. Furthermore, the related human anti-MAG monoclonal IgM antibodies from patients with neuropathy also react strongly with PMP-22, suggesting that it may be a target antigen in the pathogenesis of this disease. Purified PNS and CNS myelin from bony fish (toadfish and trout) were also shown to contain major glycoproteins, in the same 19 to 28 kDa M(r) range, that react very strongly with HNK1. It is known that fish myelin has major proteins of this size that are immunologically and structurally related to mammalian P0, and it is demonstrated here that one of the strongly HNK1-positive proteins reacted well with an antiserum raised to bovine P0. The presence of high levels of the adhesion-related HNK1 epitope on these major myelin proteins of fish suggests that this carbohydrate structure may have played a role in the molecular evolution of myelin. (C) 1993 Wiley-Liss, Inc.* C1 NIDR, NEUROBIOL & ANESTHESIOL BRANCH, BETHESDA, MD 20892 USA. NEW YORK STATE INST BASIC RES DEV DISABIL, DEPT PHARMACOL, STATEN ISL, NY 10314 USA. RP NINCDS, MOLEC & CELLULAR NEUROBIOL LAB, BLDG 49, ROOM 2A28, BETHESDA, MD 20892 USA. RI De Leon, Marino/A-6922-2009 OI De Leon, Marino/0000-0001-6576-785X NR 76 TC 75 Z9 75 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0360-4012 EI 1097-4547 J9 J NEUROSCI RES JI J. Neurosci. Res. PD AUG 1 PY 1993 VL 35 IS 5 BP 546 EP 558 DI 10.1002/jnr.490350511 PG 13 WC Neurosciences SC Neurosciences & Neurology GA LN633 UT WOS:A1993LN63300010 PM 7690857 ER PT J AU FONTVIEILLE, AM HARPER, IT FERRARO, RT SPRAUL, M RAVUSSIN, E AF FONTVIEILLE, AM HARPER, IT FERRARO, RT SPRAUL, M RAVUSSIN, E TI DAILY ENERGY-EXPENDITURE BY 5-YEAR-OLD CHILDREN, MEASURED BY DOUBLY LABELED WATER SO JOURNAL OF PEDIATRICS LA English DT Article ID BODY-COMPOSITION; (H2O)-H-2-O-18 METHOD; METABOLIC-RATE; VALIDATION; OBESITY; ADOLESCENTS; HUMANS; RISK; AGE AB Current recommendations for daily energy requirements in 5-year-old children (90 kcal/kg per day) are based on energy intake associated with normal growth. It is not known, however, how these recommendations compare with total free-living energy expenditure (TEE) and how much of TEE is related to physical activity. The TEE and the resting metabolic rate (RMR) were measured in 28 white children, aged 5 years (15 boys, 13 girls; mean (+/- SD) weight 20.1 +/- 3.4 kg; height 113 +/- 6 cm; fat 20% +/- 5%). The TEE was calculated during a 7-day period from urinary elimination rates of deuterium (H-2) and heavy oxygen (O-18) by using a modification of the two-point slope-intercept method; RMR was measured by a ventilated-hood indirect calorimeter. Physical activity indexes were also collected from questionnaires completed by the parents. Measured TEE was considerably lower than the recommended dietary allowances (1370 +/- 222 kcal/day vs 1807 +/- 310 kcal/day; p <0.0001), whereas measured RMR was slightly higher than predicted RMR (1001 +/- 119 kcal/day vs 952 +/- 78 kcal/day; p <0.001). The energy cost of physical activity accounted for only 16% +/- 7% of TEE. An index of activity, assessed as the difference between the measured TEE and the predicted TEE, correlated positively with past-year sport-leisure activity assessed by questionnaire (r = 0.40; p <0.05). We conclude that measured TEE in 5-year-old children yields lower values (almost-equal-to 400 kcal/day) than current estimates. A minute part of this difference (20 to 30 kcal/day) is related to the changes in energy stores during growth, but most seems due to lower-than-expected levels of physical activity. This might be related to increased television viewing, which replaces activities requiring energy. RP FONTVIEILLE, AM (reprint author), NIDDKD, CLIN DIABET & NUTR SECT, PHOENIX, AZ 85016 USA. NR 40 TC 76 Z9 79 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD AUG PY 1993 VL 123 IS 2 BP 200 EP 207 DI 10.1016/S0022-3476(05)81689-0 PG 8 WC Pediatrics SC Pediatrics GA LR295 UT WOS:A1993LR29500004 PM 8345414 ER PT J AU ABRAMS, SA SILBER, TJ ESTEBAN, NV VIEIRA, NE STUFF, JE MEYERS, R MAJD, M YERGEY, AL AF ABRAMS, SA SILBER, TJ ESTEBAN, NV VIEIRA, NE STUFF, JE MEYERS, R MAJD, M YERGEY, AL TI MINERAL BALANCE AND BONE TURNOVER IN ADOLESCENTS WITH ANOREXIA-NERVOSA SO JOURNAL OF PEDIATRICS LA English DT Article ID CALCIUM-METABOLISM; OSTEOPOROSIS; FRACTURES; SKELETAL; OSTEOPENIA; EXCRETION; CHILDREN; WOMEN; GIRLS; MASS AB We evaluated seven female adolescents with anorexia nervosa to determine whether calcium metabolism was affected by their disorder. We measured calcium absorption, urinary calcium excretion, and calcium kinetics, using a dual-tracer, stable-isotope technique during the first weeks of an inpatient nutritional rehabilitation program. Results were compared with those from a control group of seven healthy adolescent girls of similar ages. The percentage of absorption of calcium was lower in subjects with anorexia nervosa than in control subjects (16.2% +/- 6.3% vs 24.6% +/- 7.2%; p <0.05). Urinary calcium excretion was greater in subjects with anorexia nervosa than in control subjects (6.4 +/- 2.5 vs 1.6 +/- 0.7 mg . kg-1 . day-1; p <0.01) and was associated with bone resorption rather than calcium hyperabsorption. Calcium kinetic studies demonstrated a decreased rate of bone formation and an increased rate of bone resorption. These results suggest marked abnormalities in mineral metabolism in patients with anorexia nervosa. From these results, we hypothesize that improvement in bone mineralization during recovery from anorexia nervosa will require resolution of hormonal abnormalities, including hypercortisolism, in addition to increased calcium intake. C1 CHILDRENS NATL MED CTR, DEPT ADOLESCENT & YOUNG ADULT MED, WASHINGTON, DC USA. NICHHD, THEORET & PHYS BIOL LAB, BETHESDA, MD 20892 USA. RP ABRAMS, SA (reprint author), BAYLOR COLL MED, USDA ARS, CHILDRENS NUTR RES CTR, DEPT PEDIAT, 1100 BATES ST, HOUSTON, TX 77030 USA. OI Abrams, Steven/0000-0003-4972-9233 NR 32 TC 48 Z9 50 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD AUG PY 1993 VL 123 IS 2 BP 326 EP 331 DI 10.1016/S0022-3476(05)81714-7 PG 6 WC Pediatrics SC Pediatrics GA LR295 UT WOS:A1993LR29500029 PM 8345437 ER PT J AU MANASCO, PK PESCOVITZ, OH BLIZZARD, RM AF MANASCO, PK PESCOVITZ, OH BLIZZARD, RM TI LOCAL REACTIONS TO DEPOT LEUPROLIDE THERAPY FOR CENTRAL PRECOCIOUS PUBERTY SO JOURNAL OF PEDIATRICS LA English DT Letter C1 UNIV N CAROLINA, DIV PEDIAT ENDOCRINOL, CHAPEL HILL, NC 27759 USA. INDIANA UNIV, RILEY CHILDRENS HOSP, MED CTR, PEDIAT ENDOCRINOL DIABETOL SECT, INDIANAPOLIS, IN 46202 USA. UNIV VIRGINIA, HLTH SCI CTR, DEPT PEDIAT, CHARLOTTESVILLE, VA 22908 USA. RP MANASCO, PK (reprint author), NIEHS, MOLEC & INTEGRAT NEUROSCI LAB, RES TRIANGLE PK, NC 27709 USA. NR 1 TC 28 Z9 29 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD AUG PY 1993 VL 123 IS 2 BP 334 EP 335 DI 10.1016/S0022-3476(05)81720-2 PG 2 WC Pediatrics SC Pediatrics GA LR295 UT WOS:A1993LR29500034 PM 8345441 ER PT J AU WITKIN, JM TERRY, P MENKEL, M HICKEY, P PONTECORVO, M FERKANY, J KATZ, JL AF WITKIN, JM TERRY, P MENKEL, M HICKEY, P PONTECORVO, M FERKANY, J KATZ, JL TI EFFECTS OF THE SELECTIVE SIGMA-RECEPTOR LIGAND, 6-[6-(4-HYDROXYPIPERIDINYL)HEXYLOXY]-3-METHYLFLAVONE (NPC-16377), ON BEHAVIORAL AND TOXIC EFFECTS OF COCAINE SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID MIDBRAIN DOPAMINE NEURONS; GUINEA-PIG BRAIN; BINDING-SITES; HIGH-AFFINITY; PHENCYCLIDINE; SENSITIZATION; HALOPERIDOL; BMY-14802; AGONIST; RAT AB Certain sigma receptor ligands have been shown to block locomotor stimulation produced by cocaine at doses that do not have significant behavioral activity when given alone. Using a potent and selective ligand of sigma binding sites, 6-[6-(4-hydroxypiperidinyl)hexyloxy]-3-methylflavone (NPC 16377), we further investigated the influence of sigma ligands on additional behavioral and toxic effects of cocaine in mice. A behaviorally inactive dose of NPC 16377 shifted the dose-effect function for the locomotor stimulant effects of cocaine to the right by a factor of 2.5. A higher dose of NPC 16377 produced an insurmountable blockade of this stimulant effect of cocaine. Prior exposure to cocaine enhances the locomotor stimulant effects of cocaine (sensitization). NPC 16377 prevented the development of cocaine sensitization without producing behavioral effects of its own. However, NPC 16377 was unable to block the expression of sensitization in mice previously exposed to cocaine. NPC 16377 also did not consistently alter the discriminative stimulus effects of cocaine or methamphetamine in rats discriminating either 3 or 10 mg/kg of cocaine, or 1 mg/kg of methamphetamine from saline. The potential phencyclidine-like behavioral effects of NPC 16377 were also evaluated. Unlike the NMDA channel ligand, dizocilpine, NPC 16377 did not increase responding under a fixed-interval schedule of food presentation in rats nor did it substitute for the discriminative stimulus effects of either 1.5 mg/kg of phencyclidine or 0.2 mg/kg of dizocilpine in rats discriminating these drugs from saline. NPC 16377 displayed limited but significant anticonvulsant activity against diazepam-sensitive cocaine convulsions. The lethal effects of higher doses of cocaine were neither significantly blocked nor enhanced in rats or mice with NPC 16377. These findings extend earlier observations on the cocaine-blocking effects of sigma ligands to a novel structure with exceptional selectivity for sigma sites. These data indicate that some sigma ligands may be capable of altering certain behavioral and toxic actions of cocaine without notable behavioral side effects as evidenced in preclinical tests. As such, these compounds may ultimately be useful in the treatment of cocaine abuse. C1 NOVA PHARMACEUT CORP,BALTIMORE,MD. RP WITKIN, JM (reprint author), NIDA,ADDICT RES CTR,PSYCHOBIOL SECT,DRUG DEV GRP,POB 5180,BALTIMORE,MD 21224, USA. OI Katz, Jonathan/0000-0002-1068-1159 NR 49 TC 62 Z9 62 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 AUG PY 1993 VL 266 IS 2 BP 473 EP 482 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LT482 UT WOS:A1993LT48200001 PM 8355185 ER PT J AU WONG, G SKOLNICK, P KATZ, JL WITKIN, JM AF WONG, G SKOLNICK, P KATZ, JL WITKIN, JM TI TRANSDUCTION OF A DISCRIMINATIVE STIMULUS THROUGH A DIAZEPAM-INSENSITIVE GAMMA-AMINOBUTYRIC ACID(A) RECEPTOR SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CHLORIDE CHANNEL COMPLEX; CENTRAL-NERVOUS-SYSTEM; GABA-A RECEPTORS; BENZODIAZEPINE RECEPTORS; RO 15-1788; ALCOHOL ANTAGONIST; BINDING; HETEROGENEITY; FLUMAZENIL; LIGANDS AB Although there appear to be a large number of possible isoforms of the gamma-aminobutyric acid (GABA)A receptor, the relationship of a particular isoform to a specific behavior or behavioral process has not been identified. In the present study we describe a functional role for a diazepam-insensitive (DI) isoform of the GABA(A) receptor in the control of a complex discrimination. Pigeons were trained to discriminate the benzodiazepine antagonist flumazenil (1 00 mug/kg) from vehicle by requiring 30 keypeck responses on one key when flumazenil was given and on a different key when vehicle was given. Only ligands with high affinities for DI sites fully substituted for the discriminative stimulus effects of flumazenil. A significant positive correlation was observed between ligand affinities for DI sites and ED50 values for discriminative stimulus effects. These compounds mimicked the discriminative stimulus effects of flumazenil despite partial agonist, inverse agonist or antagonist actions at other diazepam-sensitive GABA(A) receptors. A specific role of DI GABA(A) receptors in the control of this behavior was confirmed further by the inability of either a high-affinity agonist (midazolam) or antagonist (ZK 93,426) at diazepam-sensitive receptors (that possess low affinties for DI sites) to block the discriminative stimulus effects of flumazenil. These findings establish a link between a GABA(A) receptor isoform and a specific behavior. C1 NIDA,ADDICT RES CTR,PSYCHOBIOL LAB,DRUG DEV GRP,POB 5180,BALTIMORE,MD 21224. NIDDKD,NEUROSCI LAB,BETHESDA,MD. NR 54 TC 26 Z9 26 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 AUG PY 1993 VL 266 IS 2 BP 570 EP 576 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LT482 UT WOS:A1993LT48200014 PM 8394910 ER PT J AU SZALLASI, A LEWIN, NA BLUMBERG, PM AF SZALLASI, A LEWIN, NA BLUMBERG, PM TI VANILLOID (CAPSAICIN) RECEPTOR IN THE RAT - POSITIVE COOPERATIVITY OF RESINIFERATOXIN BINDING AND ITS MODULATION BY REDUCTION AND OXIDATION SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ROOT GANGLION MEMBRANES; GENE-RELATED PEPTIDE; ACETYLCHOLINE-RECEPTOR; SULFHYDRYL-REAGENTS; OPIOID RECEPTORS; BRAIN; INVOLVEMENT; CELLS; PHARMACOLOGY; MECHANISM AB Specific [H-3]resiniferatoxin (RTX) binding is thought to represent the postulated vanilloid (capsaicin) receptor. In the present report, this binding has been reevaluated using a modified [H-3] RTX binding assay in which the high nonspecific binding, which limited the previous characterization, was reduced by adding alpha1-acid glycoprotein, a plasma protein that binds RTX, to the usual binding assay after RTX binding by the vanilloid receptor had been terminated. Specific [H-3]RTX binding by both dorsal root ganglion (DRG) and spinal cord membranes of the rat followed sigmoidal saturation kinetics indicating apparent positive cooperativity. The cooperativity index determined by fitting the data to the Hill equation was 1.7 in DRG and 1.9 in spinal cord. Apparent dissociation constants were estimated as 24 pM for DRG and 11 pM for spinal cord preparations. As predicted by the modified Hill equation, at low receptor occupancy nonradioactive agonists (RTX, tinyatoxin, capsaicin) produced biphasic competition curves. The initial (enhancement) phase of these curves correlated with the biological potency of the agonist. Dithiothreitol reduced both positive cooperativity and apparent binding affinity; the oxidizing agent 5,5'-dithiobis-(2-nitrobenzoic acid) reduced the cooperativity index without a major effect on binding affinity. These findings suggest that the vanilloid receptor is a receptor cluster in which the subunits cooperate; cooperation is, at least in part, subject to redox modulation. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 36 TC 35 Z9 35 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 AUG PY 1993 VL 266 IS 2 BP 678 EP 683 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LT482 UT WOS:A1993LT48200028 PM 8355200 ER PT J AU GU, ZF ROSSOWSKI, WJ COY, DH PRADHAN, TK JENSEN, RT AF GU, ZF ROSSOWSKI, WJ COY, DH PRADHAN, TK JENSEN, RT TI CHIMERIC GALANIN ANALOGS THAT FUNCTION AS ANTAGONISTS IN THE CNS ARE FULL AGONISTS IN GASTROINTESTINAL SMOOTH-MUSCLE SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SMALL-INTESTINE; BINDING-SITES; PEPTIDE; CELLS; RAT; HIPPOCAMPUS; RELAXATION; RECEPTORS; SECRETION; RELEASE AB Galanin has numerous effects on gastrointestinal smooth muscle. However, because of the lack of specific inhibitors, it is not known which are physiological and which are pharmacological. This study investigates the ability of two chimeric galanin analogs, [#1-galantide = (M-15) = [galanin (1-13)-substance P(5-11)] and #2-M-35[galanin(1-13)bradykinin (2-9)], which were recently reported to function as galanin-receptor antagonists in the CNS, to interact with galanin receptors on rat jejunal muscle strips or dispersed smooth muscle cells from guinea pig stomach. In both systems each chimeric analog had agonist activity and was as efficacious as galanin. Cross-desensitization experiments demonstrated that in the jejunal muscle strips, both chimeric analogs were causing muscle contraction by interacting with the galanin receptor. In dispersed smooth muscle cells, galanin, as well as each chimeric analog, caused muscle relaxation, whereas substance P and bradykinin both caused muscle contraction. Each chimeric analog was equipotent to galanin in inhibiting binding of I-125-galanin, and there was close agreement between their abilities to occupy the galanin receptor and cause relaxation. Each chimeric analog also activated adenylate cyclase and increased cAMP characteristic of relaxants. These studies demonstrate these chimeric analogs will not be useful for defining the physiological role of galanin in altering gastrointestinal motility, because they function as full galanin-receptor agonists instead of as galanin-receptor antagonists. C1 NIADDKD,DIGEST DIS BRANCH,BLDG 10,ROOM 9C-103,BETHESDA,MD 20892. NIH,BETHESDA,MD 20892. TULANE UNIV,SCH MED,DEPT MED,PEPTIDE RES LABS,NEW ORLEANS,LA 70112. NR 29 TC 58 Z9 58 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 AUG PY 1993 VL 266 IS 2 BP 912 EP 918 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LT482 UT WOS:A1993LT48200058 PM 7689105 ER PT J AU BRENNEMAN, DE PAGE, SW SCHULTZBERG, M THOMAS, FS ZELAZOWSKI, P BURNET, P AVIDOR, R STERNBERG, EM AF BRENNEMAN, DE PAGE, SW SCHULTZBERG, M THOMAS, FS ZELAZOWSKI, P BURNET, P AVIDOR, R STERNBERG, EM TI A DECOMPOSITION PRODUCT OF A CONTAMINANT IMPLICATED IN L-TRYPTOPHAN EOSINOPHILIA-MYALGIA-SYNDROME AFFECTS SPINAL-CORD NEURONAL CELL-DEATH AND SURVIVAL THROUGH STEREOSPECIFIC, MATURATION AND PARTLY INTERLEUKIN-1-DEPENDENT MECHANISMS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PEAK-E; EXPRESSION; INGESTION; CLONING; ACID; CDNA; IDENTIFICATION; NEUROTOXICITY; SUBSTANCE; TISSUES AB The L-tryptophan eosinophilia myalgia syndrome (L-TRP-EMS), an inflammatory syndrome characterized by eosinophilia, myalgias, perimyositis, fasciitis and neuropathies, occurred in epidemic proportions in the United States in the summer and fall of 1989. The neuropathic clinical features in L-TRP EMS are complex and mixed. In the present study, one of the impurities most highly associated with development Of L-TRP EMS, 1,1'-ethylidenebis[L-tryptophan] (EBT), and two of its diastereoisomeric breakdown products, were compared for evidence of neurotoxicity in vitro. In 1-month-old spinal cord cultures derived from fetal mice, synthetic (-)-(1S, 3S)-l-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (1S-beta-C) produced a 30 to 35% loss in numbers of neurons. Toxicity was not apparent after treatment with the R-isomer of the same compound or with the parent compound, EBT. Cotreatment of cultures with 1S-beta-C and neutralizing antiserum to interleukin-1 alpha (IL-1 a), or with 1 S-beta-C and neutralizing antiserum against the murine IL-1 receptor, prevented neuronal cell death associated with 1S-beta-C. Recombinant IL-1 a also produced neuronal killing that was not additive to that observed with the 1S-beta-C treatment. In contrast, in immature spinal cord neuronal cultures, the 1S-beta-C, but not the 1R-beta-C or EBT, prevented the 30% cell death which normally occurs in these cultures. Neither neutralizing anti-IL-1 antibody, nor anti-IL-1 receptor antibody blocked the neuronal survival effect, suggesting that 1 S-beta-C induces neuronal survival through a receptor-mediated mechanism independent of IL-1. The stereospecificity suggests that these effects may be receptor mediated. These studies indicate that the 1 S-beta-C effects on neuronal survival in immature neurons are maturation-dependent, and that although the neurotoxic effects of 1 S-beta-C are receptor-mediated and linked to IL-1 alpha, the neuronal survival-promoting effects are receptor-mediated and independent of IL-1. These data support the hypothesis that 1S-beta-C can cause neuronal cell death, and imply that this compound may play a role in the etiology of some of the neuropathic features Of L-TRP-EMS. C1 NIMH,BLDG 10,ROOM 35231,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. HUDDINGE HOSP,KAROLINSKA INST,CLIN RES CTR,DIV BASIC SCI DEMENTIA,S-14186 HUDDINGE,SWEDEN. NICHHD,DEV & MOLEC PHARMACOL SECT,BETHESDA,MD 20892. RI Schultzberg, Marianne/E-7076-2014 OI Schultzberg, Marianne/0000-0002-8314-0927 NR 46 TC 48 Z9 48 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 AUG PY 1993 VL 266 IS 2 BP 1029 EP 1035 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LT482 UT WOS:A1993LT48200073 PM 8355179 ER PT J AU THURSTON, AW RHEE, SG SHUKLA, SD AF THURSTON, AW RHEE, SG SHUKLA, SD TI ROLE OF GUANINE-NUCLEOTIDE-BINDING PROTEIN AND TYROSINE KINASE IN PLATELET-ACTIVATING-FACTOR ACTIVATION OF PHOSPHOLIPASE-C IN A431 CELLS - PROPOSAL FOR DUAL MECHANISMS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID EPIDERMAL GROWTH-FACTOR; SIGNAL TRANSDUCTION MECHANISMS; FACTOR RECEPTOR; MONOCLONAL-ANTIBODY; ADP-RIBOSYLATION; PERTUSSIS TOXIN; PHOSPHORYLATION; INVOLVEMENT; EXPRESSION; STIMULATION AB A431 cells, a human epidermoid carcinoma, possess specific [H-3]platelet-activating factor (PAF) and [H-3]WEB 2086 binding sites indicating the presence of PAF receptors. PAF-stimulated PLC as determined by the increase in inositol phosphate levels. Pretreatment of A431 cells with genistein, a putative tyrosine kinase inhibitor, abolished the ability of PAF to activate PLC, whereas pretreatment with staurosporine, a protein kinase C inhibitor, potentiated the ability of PAF to activate PLC. Pretreatment of A431 cells with phorbol-12-myristate-1 3-acetate, a protein kinase C activator, blocked PAF-stimulated PLC. Overnight exposure of cells to pertussis toxin (PT) partially blocked the ability of PAF to stimulate PLC. Based on these observations the involvement of PT-sensitive and -insensitive guanine nucleotide-binding protein(s) (G-protein) as well as the role of tyrosine kinase in the activation of PLC by PAF was considered further. PT treatment of A431 cell membranes obliterated PAF-stimulated GTPase and indicated that PT-insensitive membrane-associated G-proteins were not involved in PAF actions. In alpha-toxin permeabilized cells, PT blocked GTP-gamma-S potentiation of PLC activation by PAF, thus suggesting that PT-insensitive G-proteins were not involved in PAF activation of PLC in A431 cells. PAF stimulated tyrosine kinase activity as observed with the increase in radioactivity associated with proteins immunoprecipitated with polyclonal antibodies to phosphotyrosine residues. This increase was blocked by PAF receptor antagonists, CV 6209 and TCV 309, and by pretreatment with genistein. PAF also activated the phosphorylation of pp60c-src and Src associated proteins in A431 cells. It is concluded that a dual mechanism for the activation of PLC by the PAF receptor operates. One mechanism functions through a membrane-associated PT-sensitive G-protein, whereas the other pathway is independent of G-protein mediation. Interestingly, tyrosine kinase activation is common for both mechanisms. C1 UNIV MISSOURI, SCH MED, DEPT PHARMACOL, COLUMBIA, MO 65212 USA. NHLBI, BIOCHEM LAB, BETHESDA, MD 20892 USA. FU NIAAA NIH HHS [NIAAA 5T32 AA07458]; NIDDK NIH HHS [1 K04 DK 01782, 5R01 DK 35170] NR 34 TC 28 Z9 29 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 EI 1521-0103 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD AUG PY 1993 VL 266 IS 2 BP 1106 EP 1112 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LT482 UT WOS:A1993LT48200082 PM 7689100 ER PT J AU UEKAMA, K SHIOTANI, K IRIE, T ISHIMARU, Y PITHA, J AF UEKAMA, K SHIOTANI, K IRIE, T ISHIMARU, Y PITHA, J TI PROTECTIVE EFFECTS OF CYCLODEXTRIN SULFATES AGAINST GENTAMICIN-INDUCED NEPHROTOXICITY IN THE RAT SO JOURNAL OF PHARMACY AND PHARMACOLOGY LA English DT Note ID AMINOGLYCOSIDE NEPHROTOXICITY; PHOSPHOLIPIDOSIS AB The effects of cyclodextrin sulphates on the development of rat renal dysfunction induced with gentamicin, an aminoglycoside antibiotic, were studied. Daily subcutaneous injection of gentamicin (100 mg kg-1, 14 days) developed nephrotoxicity in the rat as assessed by an increase in serum urea nitrogen and histopathological changes in the renal cortex. When cyclodextrin sulphates were given intraperitoneally at 300 mg kg-1 at 6 h intervals after gentamicin administration, they protected the rat against the drug-induced renal impairment, while the parent cyclodextrins were ineffective. Since post-administration of cyclodextrin sulphates did not reduce the total amount of gentamicin accumulated in the kidney, the protection may occur through interference with intracellular events leading from the drug accumulation to nephrotoxicity. These results suggest that cyclodextrin sulphates are particularly effective in preventing renal failure associated with aminoglycoside treatment. C1 KUMAMOTO UNIV HOSP,DEPT SURG PATHOL,KUMAMOTO 860,JAPAN. NIH,NIA,GRC,BALTIMORE,MD 21224. RP UEKAMA, K (reprint author), KUMAMOTO UNIV,FAC PHARMACEUT SCI,5-1 OE HONMACHI,KUMAMOTO 862,JAPAN. RI Uekama, Kaneto/G-9890-2011 NR 15 TC 20 Z9 20 U1 1 U2 6 PU ROYAL PHARMACEUTICAL SOC GREAT BRITAIN PI LONDON PA 1 LAMBETH HIGH ST, LONDON, ENGLAND SE1 7JN SN 0022-3573 J9 J PHARM PHARMACOL JI J. Pharm. Pharmacol. PD AUG PY 1993 VL 45 IS 8 BP 745 EP 747 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LV053 UT WOS:A1993LV05300013 PM 7901374 ER PT J AU HICKS, JE MILLER, F PLOTZ, P CHEN, TH GERBER, L AF HICKS, JE MILLER, F PLOTZ, P CHEN, TH GERBER, L TI ISOMETRIC-EXERCISE INCREASES STRENGTH AND DOES NOT PRODUCE SUSTAINED CREATININE PHOSPHOKINASE INCREASES IN A PATIENT WITH POLYMYOSITIS SO JOURNAL OF RHEUMATOLOGY LA English DT Note DE POLYMYOSITIS; ISOMETRIC EXERCISE; STRENGTH AB A patient with active stable idiopathic polymyositis received a 4-week supervised right quadriceps and biceps isometric strengthening program. He demonstrated a significant increase in isometric peak torque without a sustained rise in creatinine phosphokinase (CPK). A significant decrease in postexercise CPK occurred at the end of the exercise program. We conclude a randomized clinical trial using a nonexercised patient group vs an exercised patient group may be useful. RP HICKS, JE (reprint author), NIH,DEPT REHABIL MED,9000 ROCKVILLE PIKE,10-6S235,BETHESDA,MD 20892, USA. OI Miller, Frederick/0000-0003-2831-9593 NR 8 TC 34 Z9 36 U1 0 U2 3 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD AUG PY 1993 VL 20 IS 8 BP 1399 EP 1401 PG 3 WC Rheumatology SC Rheumatology GA LV464 UT WOS:A1993LV46400028 PM 8230026 ER PT J AU GOMELLA, LG EHYA, H STEINBERG, SM RUPP, M MERINO, M ROBERTSON, C LINEHAN, WM AF GOMELLA, LG EHYA, H STEINBERG, SM RUPP, M MERINO, M ROBERTSON, C LINEHAN, WM TI FLOW CYTOMETRIC DNA ANALYSIS OF INTERLEUKIN-2 RESPONSIVE RENAL-CELL CARCINOMA SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE FLOW CYTOMETRY; INTERLEUKIN-2; RENAL CELL CARCINOMA ID DEOXYRIBONUCLEIC-ACID CONTENT; HIGH-DOSE INTERLEUKIN-2; ACTIVATED KILLER-CELLS; NEURO-BLASTOMA; CANCER; THERAPY; PLOIDY; FRESH AB Adoptive immunotherapy using interleukin-2 (IL-2) based therapy can result in marked tumor regression in some patients with metastatic renal cell carcinoma. DNA flow cytometry has not been previously studied as a predictor of outcome of this therapy. Archival paraffin embedded tumors were studied in 23 IL-2 treated patients with metastatic renal cell carcinoma. Eleven patients were complete responders (CR) and 12 were nonresponders (NR). In the CR group, 4/11 (40%) were diploid and 7/11 (60%) were aneuploid. In the NR group, 9/12 (75%) were diploid and 3/12 (25%) were aneuploid. Although there was a trend that patients with an aneuploid DNA pattern were more likely to undergo a complete response, ploidy pattern alone was not significantly predictive of response (p2 = 0. 10, Fischer's exact test). When combining ploidy pattern with other variables that were predictive for complete response, such as good performance status and a higher pretreatment weight, prediction of complete response was not improved by including ploidy. This preliminary report suggests that DNA ploidy does not appear to provide any additional information concerning responsiveness to IL-2 based immunotherapy beyond that obtained by performance status and pretreatment weight in this patient population. (C) 1993 Wiley-Liss, Inc.* C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PATHOL,PHILADELPHIA,PA 19107. NCI,SURG BRANCH,BETHESDA,MD 20892. NCI,PATHOL BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. RP GOMELLA, LG (reprint author), THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT UROL,1025 WALNUT ST,PHILADELPHIA,PA 19107, USA. NR 18 TC 2 Z9 2 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 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD AUG PY 1993 VL 53 IS 4 BP 252 EP 255 DI 10.1002/jso.2930530413 PG 4 WC Oncology; Surgery SC Oncology; Surgery GA LP659 UT WOS:A1993LP65900010 PM 8341057 ER PT J AU IWASA, KH CHADWICK, RS AF IWASA, KH CHADWICK, RS TI FACTORS INFLUENCING THE LENGTH CHANGE OF AN AUDITORY OUTER HAIR CELL IN A TIGHT-FITTING CAPILLARY SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Letter ID FORCE GENERATION; ELASTICITY AB A membrane theory with area and shear moduli is used to interpret an experimental configuration used by Zenner et al. [Acta Otolaryngol. 112, 248-253]. In that experiment an outer hair cell is drawn into a tight-fitting glass capillary and a negative pressure is applied to characterize the elasticity of the cell. Various assumptions concerning membrane permeability and wall friction, which cannot readily be evaluated, are needed to interpret the data obtained in that experiment. For this reason only an upper bound of the elastic moduli, corresponding to vanishing wall friction and basal end flow conductance, can be obtained from their experimental design. In this limit, the experimental data obtained by Zenner et al. do not contradict the values of elastic moduli previously determined by internal pressurization of the cell. C1 NCRR,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RP IWASA, KH (reprint author), NIDCD,CELLULAR BIOL LAB,BETHESDA,MD 20892, USA. OI Iwasa, Kuni/0000-0002-9397-7704 NR 6 TC 4 Z9 4 U1 0 U2 1 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD AUG PY 1993 VL 94 IS 2 BP 1156 EP 1159 DI 10.1121/1.406965 PN 1 PG 4 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA LT174 UT WOS:A1993LT17400060 PM 8370870 ER PT J AU Hecht, GM Klijes, HG Roberts, WC Maron, BJ AF Hecht, Gabriela M. Klijes, Heinrich G. Roberts, William C. Maron, Barry J. TI Coexistence of Sudden Cardiac Death and End-Stage Heart Failure in Familial Hypertrophic Cardiomyopathy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article AB Objectives. The purpose of this study to determine the occurrence of sudden cardiac death of end-stage heart failure, two phases of the natural history hypertrophic cardiomyopathy, in closely related relatives. Background. Hypertrophic cardiomyopathy is a genetically transmitted cardiac disease with a particularly diverse clinical and morphologic spectrum. Premature death usually occur either suddenly or as a result of progressive congestive heart failure. Methods. We describe seven families with genetically transmitted hypertrophic cardiomyopathy that were studied with echocardiography or necropsy, or both, and were selected because they were known to include relatives who had incurred either premature sudden cardiac death or the end-stage phase of the disease. Results. The seven families comprised 128 relatives; 26 died suddenly, and 9 developed end-stage heart failure (including 2 with heart transplantation) associated with left ventricular cavity enlargement, wall thinning or decreased contractility, alone or in combination, as well as loss of outflow obstruction. Patients who died suddenly did so at younger ages (23 +/- 10 years) than did patients who died or required heart transplantation in the end-stage phase of hypertrophic cardiomyopathy (42 +/- 8 years, p < 0.001). Conclusions. This study demonstrate that family members with hypertrophic cardiomyopathy, despite a common genetic substrate, may exibit markedly diverse and distinct exopressions of the natural history of their disease, which occur at widely separated periods of life. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Pathol Branch, NIH, Bethesda, MD 20892 USA. RP Maron, BJ (reprint author), Minneapolis Heart Inst, Cardiovasc Res Div, 920 East 28th St, Minneapolis, MN 55407 USA. NR 40 TC 51 Z9 52 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 AUG PY 1993 VL 22 IS 2 BP 489 EP 497 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V42RN UT WOS:000209631000019 PM 8335819 ER PT J AU GARRISON, RJ AF GARRISON, RJ TI HEALTHY ADIPOSITY IN WOMEN - THE FRAMINGHAM OFFSPRING STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Article; Proceedings Paper CT SYMP ON WOMENS HEALTH AND NUTRITION RESEARCH : US GOVERNMENTAL CONCERN, AT THE 33RD ANNUAL MEETING OF THE AMERICAN COLLEGE OF NUTRITION CY OCT, 1992 CL SAN DIEGO, CA SP AMER COLL NUTR DE OBESITY; BODY WEIGHT; ADIPOSE TISSUE; SKINFOLD THICKNESS; CARDIOVASCULAR DISEASE ID LEFT-VENTRICULAR MASS; BLOOD-PRESSURE; BODY-WEIGHT AB This report estimates a threshold for ''healthy adiposity'' by determining the relationship between subscapular skinfolds thickness, a direct measure of adiposity, and cardiovascular disease risk factors in 1254 nonsmoking adult women who participated in the Framingham Offspring Study. Cardiovascular disease risk factors, including blood pressure, fasting plasma lipoprotein cholesterol, plasma glucose and echocardiographically measured left ventricular mass, were included. The optimal subscapular skinfold for 20-39-year-old women was determined to be < 15 mm. Women aged 20-59 whose subscapular skinfolds were below this level had a mean body mass index (BMI) of 21.1 kg/M2. Weight-for-height estimates for these women corresponded closely to the 1959 Metropolitan Life Insurance Company Desirable Weight table. The probability of having unhealthy adiposity was estimated for all women aged 20-59 for each (rounded) integer value grouping of BMI. The probability of being above the healthy adiposity threshold rises rapidly across BMI levels >20 and plateaus >24. Thus, only women with BMI <24 need assessment for adiposity status. RP GARRISON, RJ (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,EPIDEMIOL & BIOMETRY PROGRAM,BETHESDA,MD 20892, USA. NR 16 TC 3 Z9 3 U1 0 U2 0 PU AMER COLL NUTRITION PI NEW YORK PA C/O HOSP. JOINT DIS. 301 E. 17TH ST., NEW YORK, NY 10003 SN 0731-5724 J9 J AM COLL NUTR JI J. Am. Coll. Nutr. PD AUG PY 1993 VL 12 IS 4 BP 357 EP 362 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA LP805 UT WOS:A1993LP80500006 PM 8409095 ER PT J AU OFFUTT, EG CATAKIS, A AF OFFUTT, EG CATAKIS, A TI JONES,EDITH - 1920-1993 SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Item About an Individual C1 MARRIOTT MANAGEMENT SERV,WASHINGTON,DC. RP OFFUTT, EG (reprint author), NIH,CTR CLIN,PATIENT DIETET SERV,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 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 AUG PY 1993 VL 93 IS 8 BP 917 EP 917 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA MA344 UT WOS:A1993MA34400022 ER PT J AU CLARFIELD, AM FOLEY, JM AF CLARFIELD, AM FOLEY, JM TI THE AMERICAN AND CANADIAN CONSENSUS CONFERENCES ON DEMENTIA - IS THERE CONSENSUS SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID IMAGING PROCEDURE CT; ALZHEIMERS-DISEASE; DIAGNOSIS; GUIDELINES; WORKUP; VIEW; MRI C1 CASE WESTERN RESERVE UNIV HOSP,CLEVELAND,OH 44106. NIH,CHAIR CONSENSUS CONFERENCE DIFFERENTIAL DIAG DEMENTING DIS,BETHESDA,MD 20892. MCGILL UNIV,SIR MORTIMER B DAVIS JEWISH GEN HOSP,MONTREAL H3A 2T5,QUEBEC,CANADA. RP CLARFIELD, AM (reprint author), SARAH HERZOG MEM HOSP,POB 35300,IL-91351 JERUSALEM,ISRAEL. NR 34 TC 13 Z9 13 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 1993 VL 41 IS 8 BP 883 EP 886 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA LQ677 UT WOS:A1993LQ67700018 PM 8340569 ER PT J AU BARR, R FOLEY, D AF BARR, R FOLEY, D TI DRIVING WITH COGNITIVE IMPAIRMENT SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter RP BARR, R (reprint author), NIA,BETHESDA,MD 20892, USA. NR 2 TC 3 Z9 3 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 1993 VL 41 IS 8 BP 889 EP 890 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA LQ677 UT WOS:A1993LQ67700027 PM 8340575 ER PT J AU PERKINS, JR SMITH, B GALLAGHER, RT JONES, DS DAVIS, SC HOFFMAN, AD TOMER, KB AF PERKINS, JR SMITH, B GALLAGHER, RT JONES, DS DAVIS, SC HOFFMAN, AD TOMER, KB TI APPLICATION OF ELECTROSPRAY MASS-SPECTROMETRY AND MATRIX-ASSISTED LASER-DESORPTION IONIZATION TIME-OF-FLIGHT MASS-SPECTROMETRY FOR MOLECULAR-WEIGHT ASSIGNMENT OF PEPTIDES IN COMPLEX-MIXTURES SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID DENDROASPIS-POLYLEPIS-POLYLEPIS; AMINO-ACID-SEQUENCE; SNAKE-VENOM TOXINS; ATMOSPHERIC-PRESSURE; ALPHA-NEUROTOXIN; BIOMOLECULES; PROTEINS; PURIFICATION; ANGUSTICEPS; PRINCIPLES AB Electrospray mass spectrometry (ES/MS) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI/TOF/MS) were used to provide mass spectra from seven elapid snake venoms. Spectral interpretation was much simpler for MALDI/TOF/MS. ES/MS proved more useful for the provision of molecular weight data for very closely related peptides, but suppression of higher molecular weight compounds was seen to occur during flow injection analysis. MALDI/TOF/MS proved useful for providing a complete picture of the venom, but the low resolution led to obscuring of major ions, and the mass accuracy was poorer for known peptides. Suppression also occurred during MALDI/TOF/MS but could be overcome using alternative matrices because the spectra were very dependent on the choice of matrix. ES/MS and MALDI/TOF/MS provide complementary and confirmatory information such that for the analysis of complex peptide mixtures (snake venoms), the use of both techniques is desirable. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP PERKINS, JR (reprint author), KRATOS ANALYT,BARTON DOCK RD,MANCHESTER M31 2LD,ENGLAND. RI Tomer, Kenneth/E-8018-2013 NR 51 TC 41 Z9 41 U1 1 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD AUG PY 1993 VL 4 IS 8 BP 670 EP 684 DI 10.1016/1044-0305(93)85032-S PG 15 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA LP546 UT WOS:A1993LP54600009 PM 24227671 ER PT J AU ARNONE, A MERLINI, L MONDELLI, R NASINI, G RAGG, E SCAGLIONI, L WEISS, U AF ARNONE, A MERLINI, L MONDELLI, R NASINI, G RAGG, E SCAGLIONI, L WEISS, U TI NMR-STUDY OF TAUTOMERISM IN NATURAL PERYLENEQUINONES SO JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 2 LA English DT Article ID SECONDARY MOLD METABOLITES; PROTEIN KINASE-C; COUPLING-CONSTANTS; MAGNETIC-RESONANCE; HYDROGEN-BONDS; NAPHTHAZARIN; STEREOCHEMISTRY; CLADOSPORIUM; CERCOSPORIN; DEUTERIUM AB The keto-enol tautomerism of the dihydroxyperylenequinone system of a number of natural compounds, cercosporin 1, isocercosporin 2, phleichrome 3, isophleichrome 4, elsinochromes 5-9, cladochrome C 10, and hypocrellin 11 was studied by H-1, H-2 and C-13 NMR spectroscopy. 4,9-Dihydroxyperlene-3,10-dione and 3,10-dihydroxyperylene-4,9-dione tautomers were recognized as present in fast equilibrium in CDCl3 and [H-2(6)]acetone solutions. The populations of each tautomer were obtained from the coupling between the proton of the hydrogen-bonded OH groups and the adjacent carbon atoms, i.e. J(C3, OH) and J(C4, OH). The most important factors governing the tautomeric equilibrium in these helix-shaped compounds appeared to be the substituent effects, the strength of the intramolecular phenol-quinone hydrogen bond, the distortion from the planarity of the perylene-quinone system, solvation and aggregation effects. The strength of the hydrogen bonds, which is related to the distortion from planarity, was evaluated from H-1 chemical shifts and primary deuterium isotope effects. Proton shifts of OH groups and isotope effects are linearly correlated. The influence of solvents and concentration on the tautomeric equilibrium was studied in the case of 4, for which a model of vertical stacking-type dimerisation is proposed. C1 UNIV MILAN,SEZ CHIM,DIPARTIMENTO SCI MOLEC AGROALIMENTARI,VIA CELORIA 2,I-20133 MILAN,ITALY. POLITECN MILAN,DIPARTIMENTO CHIM,CNR,CTR SOSTANZE ORGAN NAT,I-20133 MILAN,ITALY. NIDDK,CHEM PHYS LAB,BETHESDA,MD. OI RAGG, ENZIO MARIA/0000-0002-2757-8369 NR 38 TC 17 Z9 17 U1 1 U2 6 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK MILTON ROAD, CAMBRIDGE, CAMBS, ENGLAND CB4 4WF SN 0300-9580 J9 J CHEM SOC PERK T 2 JI J. Chem. Soc.-Perkin Trans. 2 PD AUG PY 1993 IS 8 BP 1447 EP 1454 DI 10.1039/p29930001447 PG 8 WC Chemistry, Organic; Chemistry, Physical SC Chemistry GA LT048 UT WOS:A1993LT04800009 ER PT J AU LIJINSKY, W RIGGS, CW WALTERS, PT AF LIJINSKY, W RIGGS, CW WALTERS, PT TI LACK OF EFFECT OF CARCINOGEN TREATMENT ON DEVELOPMENT OF TUMORS ARISING SPONTANEOUSLY IN FISCHER-344 RATS SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH LA English DT Article ID GAVAGE; SURVIVAL; METHYL AB The incidence of a set of neoplasms arising ''spontaneously'' in Fischer 344 (F344) rats was determined in control and carcinogen-treated animals. Data were obtained from approximately 9000 rats (4000 males and 5000 females) used to study the carcinogenicity of a variety of alkylating compounds, including N-nitroso compounds, azoxyalkanes, and triazenes. In these experiments treated rats and controls were allowed to die naturally and were necropsied, and the tissues were examined histopathologically. The spontaneous neoplasms of interest were mononuclear cell leukemia and neoplasms of the anterior pituitary, adrenal medulla, pancreas, thyroid gland, mammary gland, and testis. These tumors were generally absent from control animals that (rarely) died before 70 wk of age. Although many carcinogen-treated rats died early with treatment-related tumors, a substantial number (1700 males and 2300 females) survived as long as controls. The incidence of spontaneous neoplasms was determined among controls and chemically treated rats at 10-wk intervals from 0 to 140 wk. The incidence of spontaneous tumors was not higher and was frequently statistically lower among treated rats than the corresponding incidence in controls, with the exception of leukemia in female rats. The same result was obtained with the subset of carcinogens not requiring metabolic activation (mostly alkylnitrosoureas). These data indicate that in this rat tumor model system, the alkylating carcinogens, while capable collectively of tumor induction at more than 20 sites, did not accelerate the development of any of the six spontaneously arising solid tumors. This suggests that these spontaneous tumors might arise by a mechanism that is unresponsive to the actions of the alkylating carcinogens. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,DATA MANAGEMENT SERV INC,FREDERICK,MD 21701. FU NCI NIH HHS [N01-CO-74101] NR 16 TC 8 Z9 8 U1 0 U2 0 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0098-4108 J9 J TOXICOL ENV HEALTH JI J. Toxicol. Environ. Health PD AUG PY 1993 VL 39 IS 4 BP 527 EP 538 PG 12 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA LT184 UT WOS:A1993LT18400008 PM 8345536 ER PT J AU MARCUS, SG CHOYKE, PL REITER, R JAFFE, GS ALEXANDER, RB LINEHAN, WM ROSENBERG, SA WALTHER, MM AF MARCUS, SG CHOYKE, PL REITER, R JAFFE, GS ALEXANDER, RB LINEHAN, WM ROSENBERG, SA WALTHER, MM TI REGRESSION OF METASTATIC RENAL-CELL CARCINOMA AFTER CYTOREDUCTIVE NEPHRECTOMY SO JOURNAL OF UROLOGY LA English DT Note DE KIDNEY; NEPHRECTOMY; CARCINOMA, RENAL CELL; NEOPLASM METASTASIS; NEOPLASM REGRESSION, SPONTANEOUS ID CANCER; ANGIOINFARCTION; THERAPY; UPDATE AB Fewer than 1% of patients with renal cell carcinoma are reported to experience spontaneous regression of metastatic lesions after nephrectomy. We report on 4 of 91 patients (4.4%) with metastatic renal cell carcinoma who had spontaneous regression of all metastatic lesions after cytoreductive nephrectomy. These patients were carefully selected before surgery for the ability to receive high dose interleukin-2. One patient had recurrence at 2 months, 1 had recurrence at 11 months, and 2 had no evidence of disease at 3 and 4.5 years. C1 NCI,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. RP MARCUS, SG (reprint author), NCI,SURG BRANCH,PATHOL LAB,BETHESDA,MD 20892, USA. NR 22 TC 67 Z9 68 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD AUG PY 1993 VL 150 IS 2 BP 463 EP 466 PN 1 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA LM765 UT WOS:A1993LM76500056 PM 8326579 ER PT J AU PERERA, LP MOSCA, JD RUYECHAN, WT HAYWARD, GS STRAUS, SE HAY, J AF PERERA, LP MOSCA, JD RUYECHAN, WT HAYWARD, GS STRAUS, SE HAY, J TI A MAJOR TRANSACTIVATOR OF VARICELLA-ZOSTER VIRUS, THE IMMEDIATE-EARLY PROTEIN IE62, CONTAINS A POTENT N-TERMINAL ACTIVATION DOMAIN SO JOURNAL OF VIROLOGY LA English DT Article ID HERPESVIRUS MACROMOLECULAR-SYNTHESIS; TEMPERATURE-SENSITIVE MUTANTS; COMPLETE DNA-SEQUENCE; MAMMALIAN-CELLS; MESSENGER-RNA; EARLY GENE; NUCLEOTIDE-SEQUENCE; REGULATORY PROTEINS; ALPHA-GENES; TYPE-1 AB Accumulating evidence indicates that the product of the putative immediate-early gene ORF62 (IE62) activates varicella-zoster virus (VZV) genes thought to represent all three kinetic classes, namely, immediate-early (alpha), early (beta), and late (gamma) classes, of VZV genes as well as a variety heterologous gene promoters. However, the mechanism(s) by which IE62 protein mediates transactivation of these diverse VZV and beterologous gene promoters remains to be elucidated. In this study, by using yeast GALA protein chimeras, the coding regions of VZV ORF62 possessing activation domains have been assessed. We demonstrate that the VZV IE62 protein contains a potent activation domain in the N-terminal portion of the molecule, encoded within the first 86 codons of ORF62. The predicted secondary structure profile and the acid-base composition of this IE62 domain resemble those of other transregulatory proteins whose activation is mediated through acidic, hydrophobic elements. In addition, we show that deletion of this activation domain from the 1,310-residue native IE62 protein results in ablation of the transactivator function of IE62. We also present evidence that the mutant IE62 protein lacking the activation domain, though devoid of transactivation ability, was still capable of interfering with the activation of target promoters by the native, full-length IE62. C1 HENRY M JACKSON FDN, RETROVIRUS RES LAB, ROCKVILLE, MD 20850 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT PHARMACOL & MOLEC SCI, BALTIMORE, MD 21205 USA. SUNY Buffalo, SCH MED, DEPT MICROBIOL, BUFFALO, NY 14214 USA. RP PERERA, LP (reprint author), NIAID, CLIN INVEST LAB, BETHESDA, MD 20892 USA. FU NCI NIH HHS [NIAID CA28473]; NIAID NIH HHS [NIAID AI24489, NIAID AI18449] NR 60 TC 68 Z9 69 U1 2 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 AUG PY 1993 VL 67 IS 8 BP 4474 EP 4483 PG 10 WC Virology SC Virology GA LM272 UT WOS:A1993LM27200003 PM 8392592 ER PT J AU IWASHIRO, M KONDO, T SHIMIZU, T YAMAGISHI, H TAKAHASHI, K MATSUBAYASHI, Y MASUDA, T OTAKA, A FUJII, N ISHIMOTO, A MIYAZAWA, M ROBERTSON, MN CHESEBRO, B KURIBAYASHI, K AF IWASHIRO, M KONDO, T SHIMIZU, T YAMAGISHI, H TAKAHASHI, K MATSUBAYASHI, Y MASUDA, T OTAKA, A FUJII, N ISHIMOTO, A MIYAZAWA, M ROBERTSON, MN CHESEBRO, B KURIBAYASHI, K TI MULTIPLICITY OF VIRUS-ENCODED HELPER T-CELL EPITOPES EXPRESSED ON FBL-3 TUMOR-CELLS SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; RETROVIRUS-INDUCED LEUKEMIA; LYMPHOCYTES-T; ENV GENE; SPONTANEOUS-RECOVERY; NUCLEOTIDE-SEQUENCE; ENVELOPE GENE; FRIEND; RECEPTOR; RECOMBINANT AB To identify retroviral antigenic determinants recognized by CD4+ T helper cells during tumor rejection, we established four noncytolytic, helper-type, CD4+ T-cell clones by limiting dilution cultures of mixed lymphocyte-tumor cultures from mice immune to a Friend virus-induced tumor, FBL-3. Among these, three T helper cell clones were isolated from C57BL/6 mice and the fourth was isolated from a (BALB/c x C57BL/6)F1 mouse. All these clones proliferated in response to the immunizing FBL-3 tumor cells in a major histocompatibility complex class II-restricted manner. Each clone expressed a distinct T-cell receptor with a characteristic combination of alpha and beta chains. The localization of helper T-cell determinants on viral proteins was analyzed with recombinant vaccinia viruses expressing Friend murine leukemia virus (F-MuLV) gag or env genes or shorter fragments of the env gene. Epitopes recognized by these T-cell clones were mapped to at least two distinct portions in the env region of the F-MuLV genome. These epitopes were identified more precisely with synthetic peptides derived from the F-MuLV envelope protein sequence. One of these epitopes was common to Friend and Moloney MuLVs and was located in the N-terminal region of the gp70 glycoprotein at amino acids 122 to 141. The second epitope, which was recognized in the context of hybrid I-E(b/d) major histocompatibility complex class II molecule, was located close to the C-terminal end of gp70 at amino acids 462 to 479. In addition, a possible third epitope was located in the N-terminal half of the gp70 sequence and differed from the first epitope in that it was not cross-reactive with the Moloney MuLV envelope protein, C1 KYOTO UNIV, FAC MED, INST IMMUNOL, KYOTO 606, JAPAN. KYOTO UNIV, FAC SCI, DEPT CHEM, KYOTO 606, JAPAN. KYOTO UNIV, FAC PHARMACEUT SCI, DEPT PHARMACEUT MFG, KYOTO 606, JAPAN. NIAID, ROCKY MT LABS, PERSISTENT VIRAL DIS LAB, HAMILTON, MT 59840 USA. TOHOKU UNIV, SCH MED, DEPT PATHOL, SENDAI, MIYAGI 980, JAPAN. KYOTO UNIV, FAC SCI, DEPT ELECT ENGN & COMP SCI, KYOTO 606, JAPAN. NR 51 TC 49 Z9 50 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 1993 VL 67 IS 8 BP 4533 EP 4542 PG 10 WC Virology SC Virology GA LM272 UT WOS:A1993LM27200010 PM 7687300 ER PT J AU MASUDA, M HOFFMAN, PM RUSCETTI, SK AF MASUDA, M HOFFMAN, PM RUSCETTI, SK TI VIRAL DETERMINANTS THAT CONTROL THE NEUROPATHOGENICITY OF PVC-211 MURINE LEUKEMIA-VIRUS IN-VIVO DETERMINE BRAIN CAPILLARY ENDOTHELIAL-CELL TROPISM OF THE VIRUS IN-VITRO SO JOURNAL OF VIROLOGY LA English DT Article ID COMPLETE NUCLEOTIDE-SEQUENCE; NERVOUS-SYSTEM; POLYPROTEIN; VARIANT; DNA; TRANSFECTION; INFECTION; RECEPTOR; FRAGMENT; PROTEIN AB PVC-211 murine leukemia virus (MuLV) is a neuropathogenic, weakly leukemogenic variant of the nonneuropathogenic, highly leukemogenic Friend MuLV (F-MuLV). Chimeric viruses constructed from PVC-211 MuLV clone 3d and F-MuLV clone 57 indicate that the env gene of PVC-211 MuLV contains the determinant(s) responsible for pathological changes in the central nervous system. However, sequences within the 5' one-third (AatII-EcoRI region) of the PVC-211 MuLV genome, which include the 5' leader sequence, the gag gene, and the 5' quarter of the pol gene, are also needed in conjunction with the env gene determinant(s) to cause clinically evident neurological disease in the majority of virus-infected animals after a short latency. in the presence of the AatII-EcoRI region of the PVC-211 MuLV genome, the PVC-211 MuLV env gene sequences encoding the amino-terminal half of the SU protein, which contains the receptor-binding region of the protein, were sufficient to cause rapidly progressive neurological disease. When PVC-211 MuLV, F-MuLV, and various chimeric viruses were tested for their ability to replicate in cultured brain capillary endothelial cells (BCEC), the primary site of PVC-211 MuLV replication within the central nervous system, there was a direct correlation between the replication efficiency of a virus in BCEC in vitro and its ability to cause neurological disease in vivo. This observation indicates that the sequences in PVC-211 MuLV that render it neuropathogenic affect its replication in BCEC and suggests that rapid and efficient replication of the vims in BCEC is crucial for the pathological changes in the central nervous system that result in development of neurological disease. C1 NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702. DEPT VET AFFAIRS MED CTR,RETROVIRUS RES CTR,BALTIMORE,MD 21201. NR 29 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 AUG PY 1993 VL 67 IS 8 BP 4580 EP 4587 PG 8 WC Virology SC Virology GA LM272 UT WOS:A1993LM27200015 PM 8392599 ER PT J AU PFEIFFER, B BERNEMAN, ZN NEIPEL, F CHANG, CK TIRWATNAPONG, S CHANDRAN, B AF PFEIFFER, B BERNEMAN, ZN NEIPEL, F CHANG, CK TIRWATNAPONG, S CHANDRAN, B TI IDENTIFICATION AND MAPPING OF THE GENE ENCODING THE GLYCOPROTEIN COMPLEX GP82-GP105 OF HUMAN HERPESVIRUS-6 AND MAPPING OF THE NEUTRALIZING EPITOPE RECOGNIZED BY MONOCLONAL-ANTIBODIES SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; EXANTHEM SUBITUM; SEQUENCE-ANALYSIS; PROTEIN; GENOME; HHV-6; POLYMORPHISM; LOCALIZATION; STRAINS; DNA AB Monoclonal antibodies (MAbs) 2D4, 2D6, and 13D6 against human herpesvirus 6 (HHV-6) variant A strain GS recognized virion envelope glycoprotein complex gp82-gp105 and neutralized the infectivity of HHV-6 variant A group isolates. A 624-bp genomic fragment (82G) was identified from an HHV-6 strain GS genomic library constructed in the lambdagt11 expression system by immunoscreening with MAb 2D6. Rabbit antibodies against the fusion protein expressed from the genomic insert recognized glycoprotein complex gp82-gp105 from HHV-6-infected cells, thus confirming that the genomic fragment is a portion of the gene(s) that encodes gp82-gp105. This genomic insert hybridized specifically with viral DNAs from HHV-6 variant A strains GS and U1102 under high-stringency conditions but hybridized with HHV-6 variant B strain Z-29 DNA only under low-stringency conditions. DNA sequence analysis of the insert revealed a 167-amino-acid single open reading frame with an open 5' end and a stop codon at the 3' end. Hybridization studies with HHV-6A strain U1102 DNA localized the gp82-gp105-encoding gene to the unique long region near the direct repeat at the right end of the genome. To locate the neutralizing epitope(s) recognized by the MAbs, a series of deletions from the 3' end of the gene were constructed with exonuclease III, and fusion proteins from deletion constructs were tested for reactivity with MAbs in a Western immunoblot assay. Sequencing of deletion constructs at the reactive-nonreactive transition point localized the epitope recognized by the three neutralizing MAbs within or near a repeat amino acid sequence (NIYFNIY) of the putative protein. This repeat sequence region is surrounded on either side by two potential N-glycosylation sites and three cysteine residues. C1 UNIV KANSAS,MED CTR,DEPT MICROBIOL MOLEC GENET & IMMUNOL,KANSAS CITY,KS 66160. NCI,THROMBOSIS & VASC RES LAB,BETHESDA,MD 20892. UNIV ERLANGEN NURNBERG,INST KLIN & MOLEK VIROL,W-8520 ERLANGEN,GERMANY. FU NIAID NIH HHS [AI33502, AI24224, AI30356] NR 32 TC 25 Z9 25 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 AUG PY 1993 VL 67 IS 8 BP 4611 EP 4620 PG 10 WC Virology SC Virology GA LM272 UT WOS:A1993LM27200019 PM 7687301 ER PT J AU DUNN, KJ YUAN, CC BLAIR, DG AF DUNN, KJ YUAN, CC BLAIR, DG TI A PHENOTYPIC HOST-RANGE ALTERATION DETERMINES RD114 VIRUS RESTRICTION IN FELINE EMBRYONIC-CELLS SO JOURNAL OF VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; LEUKEMIA-VIRUS; ENVELOPE GLYCOPROTEIN; MOUSE CELLS; RETROVIRAL SEQUENCES; BIOLOGICAL-ACTIVITY; 30S RNA; C VIRUS; LINE; INTEGRATION AB We have characterized the restriction mechanism for RD114 virus replication in embryonic feline cells (FeF). By comparing growth properties of the virus in FeF cells with its behavior in a fetal feline glial cell line (G355) permissive for RD114, we showed that both cell lines were readily infectible by virus grown in permissive cells and that no significant differences in viral integration or viral RNA expression could be detected. However, analysis of viral protein expression revealed differences in viral env gene processing in the two celt types. Envelope precursor pR85 was produced, but the expected processed gp70 product was detectable only in permissive (G355) cells. An envelope product of 85 kDa was packaged into virions produced by FeF celts, while virions produced by G355 cells contained the expected RD114 gp70. While the gp85 env-containing virions were infectious for permissive G355 cells, they were unable to infect FeF cells. The block to infection by the gp85-containing particles in FeF cells could be abrogated by treatment with the glycosylation inhibitor tunicamycin. Our results indicate that restriction of RD114 virus involves a novel mechanism dependent on two factors: altered glycosylation of the envelope to a gp85 form and an altered RD114 receptor in FeF cells. C1 NCI, MOLEC ONCOL LAB, FREDERICK, MD 21702 USA. TORONTO GEN HOSP, DEPT PATHOL, TORONTO M5G 1L5, ON, CANADA. NR 34 TC 17 Z9 17 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD AUG PY 1993 VL 67 IS 8 BP 4704 EP 4711 PG 8 WC Virology SC Virology GA LM272 UT WOS:A1993LM27200029 PM 8392609 ER PT J AU MORGAN, RA NUSSBAUM, O MUENCHAU, DD SHU, LM COUTURE, L ANDERSON, WF AF MORGAN, RA NUSSBAUM, O MUENCHAU, DD SHU, LM COUTURE, L ANDERSON, WF TI ANALYSIS OF THE FUNCTIONAL AND HOST RANGE-DETERMINING REGIONS OF THE MURINE ECOTROPIC AND AMPHOTROPIC RETROVIRUS ENVELOPE PROTEINS SO JOURNAL OF VIROLOGY LA English DT Article ID LEUKEMIA-VIRUS ENVELOPE; FOCUS-FORMING VIRUS; NUCLEOTIDE-SEQUENCE; ENV GENE; GLYCOPROTEIN PRECURSOR; RECEPTOR; DIMERIZATION; POLYPROTEIN; INFECTIVITY; EXPRESSION AB A series of Moloney murine leukemia virus (Mo-MuLV) envelope gene constructs were analyzed for biological activity. Three classes of recombinant envelopes were examined: insertions, deletions, and chimeras. Insertion (4 to 5 amino acids) and deletion (31 to 62 amino acids) mutants spanned most of the SU (gp70)-coding region and were all biologically inactive. Radioimmunoprecipitation demonstrated.that the mutant envelope proteins were incorrectly processed. The Pr80env envelope precursor proteins failed to obtain the proper posttranslational modifications and were not cleaved into SU (gp70) and TM (p15E), suggesting that disruption of Pr80env structure prevents intracellular transport and processing. To analyze the functional domains of the SU portion of the Env protein, we assembled several chimeric constructs. In these constructs, portions of the ecotropic Mo-MuLV envelope gene were replaced with corresponding sequences from the 4070A amphotropic MuLV envelope. Using a retroviral vector pseudotyping assay, 5 of 12 chimeric envelope proteins were shown to be biologically active. Host range was determined by retroviral vector transduction of the appropriate cell, by viral interference studies, and by the productive infection of Chinese hamster ovary cells expressing the murine ecotropic receptor. These results permit assignment of the amino acids responsible for host range determination. Ecotropic host range is determined by the first 88 amino acids of the Mo-MuLV SU, while the amphotropic host range-determining region spans the first 157 amino acids of the 4070A SU. RP MORGAN, RA (reprint author), NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892, USA. NR 44 TC 88 Z9 88 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 AUG PY 1993 VL 67 IS 8 BP 4712 EP 4721 PG 10 WC Virology SC Virology GA LM272 UT WOS:A1993LM27200030 PM 8331726 ER PT J AU WOLFFE, EJ ISAACS, SN MOSS, B AF WOLFFE, EJ ISAACS, SN MOSS, B TI DELETION OF THE VACCINIA VIRUS B5R-GENE ENCODING A 42-KILODALTON MEMBRANE GLYCOPROTEIN INHIBITS EXTRACELLULAR VIRUS ENVELOPE FORMATION AND DISSEMINATION SO JOURNAL OF VIROLOGY LA English DT Article ID NUCLEOTIDE-SEQUENCE; EXPRESSION VECTORS; CELL-FUSION; GENE; HEMAGGLUTININ; PROTEIN; RELEASE; FORMS; IDENTIFICATION; POLYPEPTIDE AB The structure, formation, and function of the virion membranes are among the least well understood aspects of vaccinia virus replication. In this study, we investigated the role of gp42, a glycoprotein component of the extracellular enveloped form of vaccinia virus (EEV) encoded by the B5R gene. The B5R gene was deleted by homologous recombination from vaccinia virus strains IHD-J and WR, which produce high and low levels of EEV, respectively. Isolation of recombinant viruses was facilitated by the insertion into the genome of a cassette containing the Escherichia coli gpt and lacZ genes flanked by the ends of the B5R gene to provide simultaneous antibiotic selection and color screening. Deletion mutant viruses of both strains formed tiny plaques, and those of the IHD-J mutant lacked the characteristic comet shape caused by release of EEV. Nevertheless, similar yields of intracellular infectious virus were obtained whether cells were infected with the B5R deletion mutants or their parental strains. In the case of IHD-J, however, this deletion severely reduced the amount of infectious extracellular virus. Metabolic labeling studies demonstrated that the low extracellular infectivity corresponded with a decrease in EEV particles in the medium. Electron microscopic examination revealed that mature intracellular naked virions (INV) were present in cells infected with mutant virus, but neither membrane-wrapped INV nor significant amounts of plasma membrane-associated virus were observed. Syncytium formation, which occurs in cells infected with wild-type WR and IHD-J virus after brief low-pH treatment, did not occur in cells infected with the B5R deletion mutants. By contrast, syncytium formation induced by antibody to the viral hemagglutinin occurred, suggesting that different mechanisms are involved. When assayed by intracranial injection into weanling mice, both IHD-J and WR mutant viruses were found to be significantly attenuated. These findings demonstrate that the 42-kDa glycoprotein of the EEV is required for efficient membrane enwrapment of INV, externalization of the virus, and transmission and that gp42 contributes to viral virulence in strains producing both low and high levels of EEV. C1 NIAID,VIRAL DIS LAB,BLDG 4,ROOM 229,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 40 TC 156 Z9 160 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 AUG PY 1993 VL 67 IS 8 BP 4732 EP 4741 PG 10 WC Virology SC Virology GA LM272 UT WOS:A1993LM27200032 PM 8331727 ER PT J AU PLETNEV, AG BRAY, M LAI, CJ AF PLETNEV, AG BRAY, M LAI, CJ TI CHIMERIC TICK-BORNE ENCEPHALITIS AND DENGUE TYPE-4 VIRUSES - EFFECTS OF MUTATIONS ON NEUROVIRULENCE IN MICE SO JOURNAL OF VIROLOGY LA English DT Article ID STRUCTURAL PROTEINS; NUCLEOTIDE-SEQUENCE; ENVELOPE GLYCOPROTEIN; FLAVIVIRUSES; GENES; GENOME; CONSTRUCTION; CARBOHYDRATE; STRAIN AB Two new chimeric flaviviruses were constructed from full-length cDNAs that contained tick-borne encephalitis virus (TBEV) CME or ME structural protein genes and the remaining genes derived from dengue type 4 virus (DEN4). Studies involving mice inoculated intracerebrally with the ME chimeric virus indicated that it retained the neurovirulence of its TBEV parent from which its pre-M and E genes were derived. However, unlike parental TBEV, the chimeric virus did not produce encephalitis when mice were inoculated peripherally, indicating a loss of neuroinvasiveness. In the present study, the ME chimeric virus (vME) was subjected to mutational analysis in an attempt to reduce or ablate neurovirulence measured by direct inoculation of virus into the brain. We identified three distinct mutations that were each associated independently with a significant reduction of mouse neurovirulence of vME. These mutations ablated (i) the TBEV pre-M cleavage site, (ii) the TBEV E glycosylation site, or (iii) the first DEN4 NS1 glycosylation site. In contrast, ablation of the second DEN4 NS1 glycosylation site or the THE pre-M glycosylation site or amino acid substitution at two positions in the TBEV E protein increased neurovirulence. The only conserved feature of the three attenuated mutants was restriction of virus yield in both simian and mosquito cells. Following parenteral inoculation, these attenuated mutants induced complete resistance in mice to fatal encephalitis caused by the highly neurovirulent vME. C1 NIAID,INFECT DIS LAB,MOLEC VIRAL BIOL SECT,BETHESDA,MD 20892. RUSSIAN ACAD SCI,INST BIOORGANIC CHEM,NOVOSIBIRSK 630090,RUSSIA. NR 28 TC 91 Z9 95 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 AUG PY 1993 VL 67 IS 8 BP 4956 EP 4963 PG 8 WC Virology SC Virology GA LM272 UT WOS:A1993LM27200056 PM 8331735 ER PT J AU MALDARELLI, F CHEN, MY WILLEY, RL STREBEL, K AF MALDARELLI, F CHEN, MY WILLEY, RL STREBEL, K TI HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 VPU PROTEIN IS AN OLIGOMERIC TYPE-I INTEGRAL MEMBRANE-PROTEIN SO JOURNAL OF VIROLOGY LA English DT Note ID HYDROPHOBIC PROTEIN; GENE; CD4; EXPRESSION; INSERTION; INFLUENZA; SEQUENCE; REQUIRES; PRODUCTS; RELEASE AB The human immunodeficiency virus type 1 Vpu protein is a 16-kDa phosphoprotein which enhances the efficiency of virion production and induces rapid degradation of CD4, the cellular receptor for human immunodeficiency virus. The topology of membrane-inserted Vpu was investigated by using in vitro-synthesized Vpu cotranslationally inserted into canine microsomal membranes. Proteolytic digestion and immunoprecipitation studies revealed that Vpu was a type I integral membrane protein, with the hydrophilic domain projecting from the cytoplasmic membrane face. In addition, several high-molecular-weight proteins containing Vpu were identified by chemical cross-linking. Such complexes also formed when wild-type Vpu and a Tat-Vpu fusion protein were coexpressed. Subsequent analysis by one- and two-dimensional electrophoresis revealed that these high-molecular-weight complexes consisted of homo-oligomers of Vpu. These findings indicate that Vpu is a type I integral membrane protein capable of multimerization. RP MALDARELLI, F (reprint author), NIH,MOLEC MICROBIOL LAB,BETHESDA,MD 20892, USA. NR 30 TC 194 Z9 195 U1 2 U2 5 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 AUG PY 1993 VL 67 IS 8 BP 5056 EP 5061 PG 6 WC Virology SC Virology GA LM272 UT WOS:A1993LM27200070 PM 8331740 ER PT J AU ALLIKMETS, R GERRARD, B STEWART, C WHITE, M DEAN, M AF ALLIKMETS, R GERRARD, B STEWART, C WHITE, M DEAN, M TI IDENTIFICATION OF P-GLYCOPROTEIN MULTIDRUG-RESISTANCE GENES FROM MODEL ORGANISMS SO LEUKEMIA LA English DT Article ID PLASMODIUM-FALCIPARUM; TRANSPORT PROTEINS; AMPLIFICATION; SUPERFAMILY; SEQUENCE; HOMOLOG; MEMBER; FAMILY; STE6 AB Using degenerate oligonucleotides from conserved portions of the ATP-binding domain of the active transporter genes, several new members of this gene superfamily have been cloned from Drosophila, Saccromyces cerevisiae, and E. coli DNA. The Drosophila and E. coli genes contain two sets of transmembrane domains and two ATP-binding domains, whereas the-yeast gene contains single transmembrane and ATP binding domains. All three genes show a high degree of similarity to the mammalian P-glycoprotein/multidrug resistance (MDR) genes. The E. coli sequence is the only known transporter gene containing both ATP and transmembrane domains in a single open reading frame. While the function of these sequences has not been determined, they may prove to be useful for developing a model to study the function of P-glycoproteins. C1 NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RP ALLIKMETS, R (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU NCI NIH HHS [N01-CO-74102] NR 24 TC 5 Z9 5 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD AUG PY 1993 VL 7 SU 2 BP S13 EP S17 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA MA479 UT WOS:A1993MA47900005 PM 8361216 ER PT J AU BOEHME, SA LENARDO, MJ AF BOEHME, SA LENARDO, MJ TI LIGAND-INDUCED APOPTOSIS OF MATURE T-LYMPHOCYTES (PROPRIOCIDAL REGULATION) OCCURS AT DISTINCT STAGES OF THE CELL-CYCLE SO LEUKEMIA LA English DT Article ID DEATH; PROLIFERATION; ALPHA AB We previously demonstrated that mature T lymphocytes responding to either IL-2 or IL-4 undergo apoptosis upon T cell antigen receptor stimulation, and have termed this potential negative feedback pathway propriocidal regulation. Using cell cycle inhibitors, we now show that T cell growth lymphokines cause the entry of T cells into vulnerable stages of the cell cycle in which T cell receptor occupancy causes apoptosis. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RP BOEHME, SA (reprint author), NCI,BIOL RESPONSE MODIFIERS PROGRAM,BETHESDA,MD 20892, USA. NR 12 TC 19 Z9 19 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD AUG PY 1993 VL 7 SU 2 BP S45 EP S49 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA MA479 UT WOS:A1993MA47900012 PM 8361232 ER PT J AU MANNS, A AF MANNS, A TI NATURAL-HISTORY OF HTLV-I INFECTION - RELATIONSHIP TO LEUKEMOGENESIS SO LEUKEMIA LA English DT Article ID T-CELL LEUKEMIA; VIRUS TYPE-I; LYMPHOMA; CLASSIFICATION; TRANSMISSION; JAMAICA; BLACKS; RISK RP MANNS, A (reprint author), NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892, USA. NR 20 TC 3 Z9 3 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD AUG PY 1993 VL 7 SU 2 BP S75 EP S77 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA MA479 UT WOS:A1993MA47900018 PM 8361238 ER PT J AU WALDMANN, TA AF WALDMANN, TA TI 1992 STOHLMAN MEMORIAL LECTURE - TARGETING THE IL-2 RECEPTOR SO LEUKEMIA LA English DT Article ID T-CELL LEUKEMIA; MULTICHAIN INTERLEUKIN-2 RECEPTOR; NON-HODGKINS LYMPHOMAS; ANTI-TAC-H; MONOCLONAL-ANTIBODY; HUMANIZED ANTIBODY; PSEUDOMONAS EXOTOXIN; GROWTH-FACTOR; EXPRESSION; LYMPHOCYTES AB Patients with human T-cell lymphotrophic virus I (HTLV-I)-associated leukemia/lymphoma were treated with different forms of IL-2 receptor (IL-2R)-directed therapy that exploit the difference in IL-2R expression between normal and malignant cells. Using unmodified anti-Tac monoclonal antibody, one-third of the patients with adult T-cell leukemia (ATL) treated have undergone a remission, in two cases complete. There was little toxicity observed; however, unmodified monoclonal antibodies are limited by their immunogenicity and their poor effector functions. To address these issues, ''humanized'' anti-Tac was produced that contains the complementarity-determining regions from the mouse with the remainder of the molecule derived from human IgG1kappa. This antibody is dramatically less immunogenic than the murine version, has improved pharmacokinetics, and, in contrast to the parent antibody, manifests antibody-dependent cellular cytotoxicity (ADCC). To enhance its effector function, anti-Tac was armed with toxins and alpha- and beta-emitting radionuclides. In a clinical trial of Y-90-anti-Tac in ATL patients, at the doses used (5, 10, and 15 mCi Y-90-anti-Tac per patient), 10 of the 15 patients with ATL treated to date underwent sustained partial or complete remission. Thus, the clinical application of IL-2R-directed therapy represents a new perspective for the prevention of allograft rejection and for the treatment of graft-versus-host disease, select autoimmune disorders, and leukemia/lymphoma. RP WALDMANN, TA (reprint author), NCI,METAB BRANCH,BETHESDA,MD 20892, USA. NR 34 TC 5 Z9 7 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD AUG PY 1993 VL 7 SU 2 BP S151 EP S156 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA MA479 UT WOS:A1993MA47900036 PM 8361223 ER PT J AU CHIRIGOS, MA DESIMONE, C AF CHIRIGOS, MA DESIMONE, C TI IMMUNOREGULATORY BIOLOGICAL RESPONSE MODIFIERS - EFFECT OF CYTOKINES ON SEPTIC SHOCK SO MEDIATORS OF INFLAMMATION LA English DT Review DE BIOLOGICAL RESPONSE MODIFIERS; CYTOKINES; INTERLEUKINS; SEPTIC SHOCK; TUMOR NECROSIS FACTOR AB WHOLE bacteria or bacterial components or their extracts were employed to restore or augment the immune system. Beneficial effects were attained with these agents in treating various diseases. These agents were named biological response modifiers (BRMs) because they regulated certain cellular components of the immune system. The cellular regulation induced by these BRMs was found to be due to cytokines. The cytokines were shown to act directly on the various cellular components and to provide therapeutic benefit in various autoimmune and immune deficiency diseases. Overproduction of specific cytokines however leads to a deleterious effect on the host. Overproduction of tumour necrosis factor (endotoxin, lipopolysaccharide) leads to septic shock. Bacteraemia is the leading cause of overproduction of tumour necrosis factor (TNF). Septic shock in many cases leads to death. Several monoclonal antibodies to lipopolysaccharide (LPS) and anticytokines have demonstrated protection against septic shock. C1 NCI,BETHESDA,MD 20892. UNIV LAQUILA,DEPT INTERNAL MED,I-67100 LAQUILA,ITALY. NR 16 TC 0 Z9 0 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0962-9351 J9 MEDIAT INFLAMM JI Mediat. Inflamm. PD AUG PY 1993 VL 2 SU 1 BP S5 EP S10 DI 10.1155/S0962935193000675 PG 6 WC Cell Biology; Immunology SC Cell Biology; Immunology GA MD662 UT WOS:A1993MD66200002 PM 18475571 ER PT J AU POTOSKY, AL RILEY, GF LUBITZ, JD MENTNECH, RM KESSLER, LG AF POTOSKY, AL RILEY, GF LUBITZ, JD MENTNECH, RM KESSLER, LG TI POTENTIAL FOR CANCER-RELATED HEALTH-SERVICES RESEARCH USING A LINKED MEDICARE-TUMOR REGISTRY DATABASE SO MEDICAL CARE LA English DT Article DE MEDICARE; TUMOR REGISTRY; CANCER; COSTS OF CANCER; PREVENTION OF CANCER ID BREAST-CANCER; RECORD LINKAGE; CLAIMS DATA; GEOGRAPHIC-VARIATION; COMPARE TREATMENTS; COST-EFFECTIVENESS; HOSPITAL VOLUME; CLINICAL-TRIALS; UNITED-STATES; LUNG-CANCER AB The National Cancer Institute and the Health Care Financing Administration share a strong research interest in cancer costs, access to cancer prevention and treatment services, and cancer patient outcomes. To develop a database for such research, the two agencies have undertaken a collaborative effort to link Medicare Program data with the Surveillance, Epidemiology, and End Results (SEER) Program database. The SEER Program is a system of 9 population-based tumor registries that collect standardized clinical information on cases diagnosed in separate, geographically defined areas covering approximately 10% of the US population. Using a deterministic matching algorithm, the records of 94% of SEER registry cases diagnosed at age 65 or older between 1973 to 1989, or more than 610,000 persons, were successfully linked with Medicare claims files. The resulting database, combining clinical characteristics with information on utilization and costs, will permit the investigation of the contribution of various patient and health care setting factors to treatment patterns, costs, and medical outcomes. C1 US HLTH CARE FINANCING ADM,DIV BENEFICIARY STUDIES,OFF RES,BALTIMORE,MD. RP POTOSKY, AL (reprint author), NCI,DIV CANC PREVENT & CONTROL,SURVEILLANCE PROGRAM,BETHESDA,MD 20892, USA. NR 67 TC 524 Z9 524 U1 1 U2 10 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD AUG PY 1993 VL 31 IS 8 BP 732 EP 748 PG 17 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA LQ995 UT WOS:A1993LQ99500006 PM 8336512 ER PT J AU LINDBERG, DAB HUMPHREYS, BL MCCRAY, AT AF LINDBERG, DAB HUMPHREYS, BL MCCRAY, AT TI THE UNIFIED MEDICAL LANGUAGE SYSTEM SO METHODS OF INFORMATION IN MEDICINE LA English DT Article DE UNIFIED MEDICAL LANGUAGE SYSTEM; UMLS; SEMANTIC NETWORK; NATIONAL-LIBRARY-OF-MEDICINE; NLM; TELECOMMUNICATION; INFORMATION MANAGEMENT; IAIMS ID INFORMATION; KNOWLEDGE AB In 1986, the National Library of Medicine began a long-term research and development project to build the Unified Medical Language System(R) (UMLS(R)). The purpose of the UMLS is to improve the ability of computer programs to ''understand'' the biomedical meaning in user inquiries and to use this understanding to retrieve and integrate relevant machine-readable information for users. Underlying the UMLS effort is the assumption that timely access to accurate and up-to-date information will improve decision making and ultimately the quality of patient care and research. The development of the UMLS is a distributed national experiment with a strong element of international collaboration. The general strategy is to develop UMLS components through a series of successive approximations of the capabilities ultimately desired. Three experimental Knowledge Sources, the Metathesaurus(R), the Semantic Network, and the Information Sources Map have been developed and are distributed annually to interested researchers, many of whom have tested and evaluated them in a range of applications. The UMLS project and current developments in high-speed, high-capacity international networks are converging in ways that have great potential for enhancing access to biomedical information. RP LINDBERG, DAB (reprint author), NATL LIB MED,BETHESDA,MD 20894, USA. NR 83 TC 581 Z9 587 U1 2 U2 18 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PD AUG PY 1993 VL 32 IS 4 BP 281 EP 291 PG 11 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA LQ714 UT WOS:A1993LQ71400007 PM 8412823 ER PT J AU BUSHMAN, JL FOIANI, M CIGAN, AM PADDON, CJ HINNEBUSCH, AG AF BUSHMAN, JL FOIANI, M CIGAN, AM PADDON, CJ HINNEBUSCH, AG TI GUANINE-NUCLEOTIDE EXCHANGE FACTOR FOR EUKARYOTIC TRANSLATION INITIATION FACTOR-II IN SACCHAROMYCES-CEREVISIAE - INTERACTIONS BETWEEN THE ESSENTIAL SUBUNITS GCD2, GCD6, AND GCD7 AND THE REGULATORY SUBUNIT GCN3 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID AMINO-ACID CONTROL; YEAST ACTIN MUTATIONS; PROTEIN-SYNTHESIS; MESSENGER-RNA; FACTOR-II; ALPHA-SUBUNIT; TRANSCRIPTIONAL ACTIVATOR; RIBOSOMAL-PROTEIN; REVERSING FACTOR; GENE AB Phosphorylation of eukarYotic translation initiation factor 2(eIF-2) in amino acid-starved cells of the yeast saccharomyces cerevisiae reduces general protein synthesis but specifically stimulates translation of GCN4 mRNA. This regulatory mechanism is dependent on the nonessential GCN3 protein and multiple essential proteins encoded by GCD genes. Previous genetic and biochemical experiments led to the conclusion that GCD1, GCD2, and GCN3 are components of the GCD complex, recently shown to be the yeast equivalent of the mammalian guanine nucleotide exchange factor for eIF-2, known as eIF-2B. In this report, we identify new constituents of the GCD-eIF-2B complex and probe interactions between its different subunits. Biochemical evidence is presented that GCN3 is an integral component of the GCD-eIF.2B complex that, while dispensable, can be mutationally altered to have a substantial inhibitory effect on general translation initiation. The amino acid sequence changes for three gcd2 mutations have been determined, and we describe several examples of mutual suppression involving the gcd2 mutations and particular alleles of GCN3. These allele-specific interactions have led us to propose that GCN3 and GCD2 directly interact in the GCD-eIF-2B complex. Genetic evidence that GCD6 and GCD7 encode additional subunits of the GCD-eEF-2B complex was provided by the fact that reduced-function mutations in these genes are lethal in strains deleted for GCN3, the same interaction described previously for mutations in GCD1 and GCD2. Biochemical experiments showing that GCD6 and GCD7 copurify and coimmunoprecipitate with GCD1, GCD2, GCN3, and subunits of eIF-2 have confirmed that GCD6 and GCD7 are subunits of the GCD-eIF-2B complex. The fact that all five subunits of yeast eIF-2B were first identified as translational regulators of GCN4 strongly suggests that regulation of guanine nucleotide exchange on eIF-2 is a key control point for translation in yeast cells just as in mammalian cells. C1 NICHHD,MOLEC GENET LAB,MOLEC GENET LOWER EUKARYOTES SECT,BETHESDA,MD 20892. RI Foiani, Marco/M-8234-2014 OI Foiani, Marco/0000-0003-4795-834X NR 54 TC 40 Z9 40 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 AUG PY 1993 VL 13 IS 8 BP 4618 EP 4631 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LN405 UT WOS:A1993LN40500018 PM 8336705 ER PT J AU CARLSON, SG FAWCETT, TW BARTLETT, JD BERNIER, M HOLBROOK, NJ AF CARLSON, SG FAWCETT, TW BARTLETT, JD BERNIER, M HOLBROOK, NJ TI REGULATION OF THE C/EBP-RELATED GENE GADD153 BY GLUCOSE DEPRIVATION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ENHANCER-BINDING-PROTEIN; 3T3-L1 PREADIPOCYTES; GROWTH ARREST; CELLS; DIFFERENTIATION; EXPRESSION; TRANSCRIPTION; DNA; PROMOTER; AGENTS AB gadd153 encodes a CCAAT/enhancer-binding protein (C/EBP)-related protein that lacks a functional DNA-binding domain. Since the gadd153 protein is capable of heterodimerizing with other C/EBPs, gadd153 may function as a negative regulator of these transcription factors. Here we examined the role of glucose in regulating gadd]53 expression. We found that glucose deprivation markedly induces gadd153 mRNA levels in both HeLa and 3T3-L1 cells and that addition of D-(+)-glucose resulted in a rapid decrease of gadd153 mRNA. Similar induction and reversal of gadd153 expression were observed at the protein level. Because C/EBPalpha appears to play an important role in regulating genes involved in adipogenesis and energy metabolism, we examined gadd153 expression during the differentiation of 3T3-L1 preadipocytes and as a function of glucose utilization in differentiated adipocytes. Using a standard differentiation protocol that consisted of hormonal stimulation for 2 days followed by medium changes every 2 days thereafter, we observed that both C/EBPalpha and gadd153 mRNAs were elevated. However, C/EBPalpha induction occurred on day 3, while gadd153 expression was not seen until day 4, when the cells were fully differentiated. Frequent addition of fresh medium to the cells during the differentiation process, as well as supplementation of medium with glucose, reduced gadd153 expression without preventing C/EBPalpha expression or interfering with cellular differentiation. Thus, gadd153 expression is not essential for the process of adipocyte differentiation but is significantly influenced by the availability of glucose to the cell. C1 NIA,MOLEC GENET LAB,BALTIMORE,MD 21224. NIA,CLIN PHYSIOL LAB,BALTIMORE,MD 21224. OI Bernier, Michel/0000-0002-5948-368X NR 33 TC 189 Z9 189 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 AUG PY 1993 VL 13 IS 8 BP 4736 EP 4744 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LN405 UT WOS:A1993LN40500029 PM 8336711 ER PT J AU HUIBREGTSE, JM SCHEFFNER, M HOWLEY, PM AF HUIBREGTSE, JM SCHEFFNER, M HOWLEY, PM TI LOCALIZATION OF THE E6-AP REGIONS THAT DIRECT HUMAN PAPILLOMAVIRUS E6 BINDING, ASSOCIATION WITH P53, AND UBIQUITINATION OF ASSOCIATED PROTEINS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CARCINOMA CELL-LINES; WILD-TYPE P53; RETINOBLASTOMA GENE-PRODUCT; CERVICAL-CARCINOMA; TUMOR-ANTIGEN; SV40-TRANSFORMED CELLS; TRANSCRIPTION FACTOR; HUMAN KERATINOCYTES; T-ANTIGEN; EXPRESSION AB E6-AP is a 100-kDa cellular protein that mediates the interaction of the human papillomavirus type 16 and 18 E6 proteins with p53. The association of p53 with E6 and E6-AP promotes the specific ubiquitination and subsequent proteolytic degradation of p53 in vitro. We recently isolated a cDNA encoding E6-AP and have now mapped functional domains of E6-AP involved in binding E6, association with p53, and ubiquitination of p53. The E6 binding domain consists of an 18-amino-acid region within the central portion of the molecule. Deletion of these 18 amino acids from E6-AP results in loss of both E6 and p53 binding activities. The region that directs p53 binding spans the E6 binding domain and consists of approximately 500 amino acids. E6-AP sequences in addition to those required for formation of a stable ternary complex with E6 and p53 are necessary to stimulate the ubiquitination of p53. These sequences lie within the C-terminal 84 amino acids of E6-AP. The entire region required for E6-dependent ubiquitination of p53 is also required for the ubiquitination of an artificial E6 fusion protein. C1 NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892. RI Scheffner, Martin/K-2940-2012 OI Scheffner, Martin/0000-0003-2229-0128 NR 46 TC 279 Z9 289 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 AUG PY 1993 VL 13 IS 8 BP 4918 EP 4927 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LN405 UT WOS:A1993LN40500048 PM 8393140 ER PT J AU ROLFES, RJ HINNEBUSCH, AG AF ROLFES, RJ HINNEBUSCH, AG TI TRANSLATION OF THE YEAST TRANSCRIPTIONAL ACTIVATOR GCN4 IS STIMULATED BY PURINE LIMITATION - IMPLICATIONS FOR ACTIVATION OF THE PROTEIN-KINASE GCN2 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID AMINO-ACID BIOSYNTHESIS; POLYPEPTIDE-CHAIN INITIATION; TRANSFER-RNA-SYNTHETASES; SACCHAROMYCES-CEREVISIAE; NUCLEOTIDE-SEQUENCE; GENERAL CONTROL; MESSENGER-RNA; EXPRESSION; CELLS; MUTATIONS AB The transcriptional activator protein GCN4 is responsible for increased transcription of more than 30 different amino acid biosynthetic genes in response to starvation for a single amino acid. This induction depends on increased expression of GCN4 at the translational level. We show that starvation for purines also stimulates GCN4 translation by the same mechanism that operates in amino acid-starved cells, being dependent on short upstream open reading frames in the GCN4 mRNA leader, the phosphorylation site in the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2alpha), the protein kinase GCN2, and translational activators of GCN4 encoded by GCN1 and GCN3. Biochemical experiments show that eIF-2alpha is phosphorylated in response to purine starvation and that this reaction is completely dependent on GCN2. As expected, derepression of GCN4 in purine-starved cells leads to a substantial increase in HIS4 expression, one of the targets of GCN4 transcriptional activation. gcn mutants that are defective for derepression of amino acid biosynthetic enzymes also exhibit sensitivity to inhibitors of purine biosynthesis, suggesting that derepression of GCN4 is required for maximal expression of one or more purine biosynthetic genes under conditions of purine limitation. Analysis of mRNAs produced from the ADE4, ADE5,7, ADE8, and ADE1 genes indicates that GCN4 stimulates the expression of these genes under conditions of histidine starvation, and it appeared that ADE8 mRNA was also derepressed by GCN4 in purine-starved cells. Our results indicate that the general control response is more global than was previously imagined in terms of the type of nutrient starvation that elicits derepression of GCN4 as well as the range of target genes that depend on GCN4 for transcriptional activation. C1 NICHHD,MOLEC GENET LAB,MOLEC GENET LOWER EUKARYOTES SECT,BETHESDA,MD 20892. NR 60 TC 89 Z9 89 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 1993 VL 13 IS 8 BP 5099 EP 5111 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LN405 UT WOS:A1993LN40500063 PM 8336737 ER PT J AU MUKHERJEE, AB MURTY, LC CHOU, JY AF MUKHERJEE, AB MURTY, LC CHOU, JY TI DIFFERENTIATION AND UTEROGLOBIN GENE-EXPRESSION BY NOVEL RABBIT ENDOMETRIAL CELL-LINES SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Note DE TRANSFORMATION; UTEROGLOBIN; STEROID HORMONE; DIFFERENTIATION; CELL LINE (RABBIT ENDOMETRIAL) ID UTERINE EPITHELIAL-CELLS; EPIDERMAL GROWTH-FACTOR; RIBONUCLEIC-ACID; RAT; ESTABLISHMENT; ESTROGEN; STIMULATION; PEPTIDES; PROTEINS AB A clear understanding of the mechanism of differentiation of mammalian endometrial epithelia would significantly improve our knowledge of embryo implantation and placentation. An ideal model for such studies would be immortal endometrial epithelial cell lines which express a well characterized, steroid-responsive, differentiation-specific gene in vitro. We characterized two cell lines which are temperature-sensitive for differentiation. At the non-permissive temperature (39.5-degrees-C), in presence of ovarian steroids, these cells express the gene coding for uteroglobin, a steroid-dependent, immunomodulatory/antiinflammatory protein in the rabbit. In addition, when cultured on artificial basement membrane (Matrigel(TM)), in presence of ovarian steroids both cell lines developed organized, tubular structures with lumens, reminiscent of an intact endometrium and secreted 33-fold more uteroglobin than the untreated controls. Thus, these immortal cell lines provide a unique model to study endometrial epithelial cell differentiation and steroid hormone action in vitro. RP MUKHERJEE, AB (reprint author), NICHHD,HUMAN GENET BRANCH,BLDG 10,ROOM 9S242,BETHESDA,MD 20892, USA. NR 30 TC 11 Z9 11 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 AUG PY 1993 VL 94 IS 2 BP R15 EP R22 DI 10.1016/0303-7207(93)90176-K PG 8 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA LU268 UT WOS:A1993LU26800013 PM 8224515 ER PT J AU ROSEN, JB ABRAMOWITZ, J POST, RM AF ROSEN, JB ABRAMOWITZ, J POST, RM TI COLOCALIZATION OF TRH MESSENGER-RNA AND FOS-LIKE IMMUNOREACTIVITY IN LIMBIC STRUCTURES FOLLOWING AMYGDALA KINDLING SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID THYROTROPIN-RELEASING-HORMONE; IMMEDIATE-EARLY GENE; C-FOS; SYNAPTIC REORGANIZATION; PYRIFORM CORTEX; RAT; PROTEINS; SEIZURE; PROENKEPHALIN; EXPRESSION RP ROSEN, JB (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892, USA. NR 44 TC 21 Z9 21 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell Neurosci. PD AUG PY 1993 VL 4 IS 4 BP 335 EP 342 DI 10.1006/mcne.1993.1043 PG 8 WC Neurosciences SC Neurosciences & Neurology GA LQ619 UT WOS:A1993LQ61900004 PM 19912940 ER PT J AU FUJITA, M SHIMADA, S NISHIMURA, T UHL, GR TOHYAMA, M AF FUJITA, M SHIMADA, S NISHIMURA, T UHL, GR TOHYAMA, M TI ONTOGENY OF DOPAMINE TRANSPORTER MESSENGER-RNA EXPRESSION IN THE RAT-BRAIN SO MOLECULAR BRAIN RESEARCH LA English DT Note DE DOPAMINE TRANSPORTER; IN-SITU HYBRIDIZATION HISTOCHEMISTRY; SUBSTANTIA-NIGRA; VENTRAL TEGMENTAL AREA; ONTOGENY ID TYROSINE-HYDROXYLASE; GENE-EXPRESSION; COCAINE; CLONING AB The ontogeny of dopamine transporter (DAT) gene expression was studied in the rat brain. DAT mRNA was first detected in neurons of the ventrocaudal mesencephalon on embryonic day 14 (E14). By E18, intensely ''pressing neurons in the ventral tegmental area and substantia nigra resembled the pattern found in adult midbrain. DAT mRNA is not abundant in the hypothalamus and the olfactory bulb at any stage of development. These results parallel those noted for tyrosine hydroxylase gene expression in mesencephalon. C1 OSAKA UNIV,SCH MED,BIOMED RES CTR,DIV TRACER KINET,SUITA,OSAKA 565,JAPAN. JOHNS HOPKINS SCH MED,NATL INST DRUG ABUSE,ADDICT RES CTR,MOLEC NEUROBIOL LAB,BALTIMORE,MD 21224. JOHNS HOPKINS SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. RP FUJITA, M (reprint author), OSAKA UNIV,SCH MED,DEPT ANAT & NEUROSCI,2-2 YAMADAOKA,SUITA,OSAKA 565,JAPAN. NR 16 TC 33 Z9 33 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD AUG PY 1993 VL 19 IS 3 BP 222 EP 226 DI 10.1016/0169-328X(93)90031-J PG 5 WC Neurosciences SC Neurosciences & Neurology GA LN816 UT WOS:A1993LN81600008 ER PT J AU SZAPARY, D OSHIMA, H SIMONS, SS AF SZAPARY, D OSHIMA, H SIMONS, SS TI A NEW CIS-ACTING ELEMENT INVOLVED IN TISSUE-SELECTIVE GLUCOCORTICOID INDUCIBILITY OF TYROSINE AMINOTRANSFERASE GENE-EXPRESSION SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID RAT HEPATOMA-CELLS; EXTINGUISHER LOCUS; RESPONSIVE ELEMENT; BINDING PROTEIN; TRANSCRIPTION; LIVER; INDUCTION; ENHANCER; PROMOTER; RECEPTORS AB Tyrosine aminotransferase (TAT), a prototypical steroid hormone-inducible gene, has been used extensively in studies of tissue-specific control of gene transcription. Over the last several years, a total of five cis-acting elements have been implicated in the tissue-specific expression and induction of the TAT gene in rat liver. These elements are all located upstream of the start of transcription, at -11, -5.5, -3.6, -2.5, and approximately -0.1 kilobases (kb). We now have used both stable and transient transfection assays to define a new element between -2.56 and -2.3 kb that regulates the fold induction by glucocorticoids in a tissue-selective manner. Compared to simple glucocorticoid-regulated constructs, which were used as controls, the major effect of this element was repression of glucocorticoid inducibility in nonliver cells. This activity was both orientation and position independent and was seen with homologous and heterologous promoters and genes. Although this element, therefore, possessed silencer-like activity, it was unable to extinguish gene expression in nonliver cells. In fact, the observance of some glucocorticoid-induced gene expression was additional evidence that the repression derived from an element that is distinct from the glucocorticoid-responsive element at -2.5 kb. A second element was found between -2.95 and -2.56 kb that acts in a tissue nonspecific manner to reduce the absolute level of gene expression in both hepatic and nonhepatic cells. The combined effects of this tissue-nonselective element and the above-mentioned tissue-selective element were to almost completely eliminate glucocorticoid inducibility in non-hepatic cells. C1 NIDDKD,MOLEC & CELLULAR BIOL LAB,STEROID HORMONES SECT,BETHESDA,MD 20892. NR 47 TC 23 Z9 23 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD AUG PY 1993 VL 7 IS 8 BP 941 EP 952 DI 10.1210/me.7.8.941 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LV205 UT WOS:A1993LV20500001 PM 7901758 ER PT J AU IGNARTROWBRIDGE, DM TENG, CT ROSS, KA PARKER, MG KORACH, KS MCLACHLAN, JA AF IGNARTROWBRIDGE, DM TENG, CT ROSS, KA PARKER, MG KORACH, KS MCLACHLAN, JA TI PEPTIDE GROWTH-FACTORS ELICIT ESTROGEN RECEPTOR-DEPENDENT TRANSCRIPTIONAL ACTIVATION OF AN ESTROGEN-RESPONSIVE ELEMENT SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID ENDOMETRIAL ADENOCARCINOMA CELLS; BREAST-CANCER CELLS; SIGNAL TRANSDUCTION; PROGESTERONE-RECEPTOR; GENE-EXPRESSION; PROTEIN-KINASE; MOUSE UTERUS; PHOSPHORYLATION; IDENTIFICATION; BINDING AB Epidermal growth factor (EGF) elicits estrogen receptor (ER)-dependent physiological sequelae and estrogen-like biochemical effects on the ER in the mouse uterus. These in vivo observations indicate that EGF may elicit some of its actions by activation of the ER. The effect of peptide growth factors on activation of a consensus estrogen-responsive element was assessed in a strain of Ishikawa human endometrial adenocarcinoma cells with negligible levels of ERs, as determined by Western blot and [H-3]estradiol binding, and in BG-1 human ovarian adenocarcinoma cells, which contain abundant ERs. EGF and transforming growth factor-alpha induced transcriptional activation of a consensus ERE in an ER-dependent manner in both cell types. Transcriptional activation by the growth factors was inhibited by ICI 164,384, an ER receptor antagonist, and neutralizing antibodies to the EGF receptor. Immunodetection of the ER in BG-1 cells demonstrated that receptor levels were not induced by transforming growth factor-alpha vs. untreated cells. ER deletion mutants containing amino acids 1-339 and 121-599 were transfected into Ishikawa cells. The 1-339 mutant was more active in inducing transcription after EGF treatment than the 121-599 mutant. Estrogen only stimulated transcription in the presence of the 121-599 mutant, while 1-339 was inactive. Interestingly, synergism between a physiological dose of estrogen and peptide growth factors was observed. The presence of cross-talk between EGF receptor and ER signaling pathways suggests that interactions between growth factors and steroid receptors may modulate hormonal activity influencing normal and aberrant function in mammalian cells. C1 IMPERIAL CANC RES FUND, MOLEC ENDOCRINOL LAB, LONDON WC2A 3PX, ENGLAND. RP IGNARTROWBRIDGE, DM (reprint author), NIEHS, REPROD & DEV TOXICOL LAB, POB 12233, E4-06, RES TRIANGLE PK, NC 27709 USA. OI Korach, Kenneth/0000-0002-7765-418X NR 35 TC 303 Z9 310 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD AUG PY 1993 VL 7 IS 8 BP 992 EP 998 DI 10.1210/me.7.8.992 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LV205 UT WOS:A1993LV20500006 PM 8232319 ER PT J AU KOSUGI, S OKAJIMA, F BAN, T HIDAKA, A SHENKER, A KOHN, LD AF KOSUGI, S OKAJIMA, F BAN, T HIDAKA, A SHENKER, A KOHN, LD TI SUBSTITUTIONS OF DIFFERENT REGIONS OF THE 3RD CYTOPLASMIC LOOP OF THE THYROTROPIN (TSH) RECEPTOR HAVE SELECTIVE EFFECTS ON CONSTITUTIVE, TSH-RECEPTOR, AND TSH-RECEPTOR AUTOANTIBODY-STIMULATED PHOSPHOINOSITIDE AND 3',5'-CYCLIC ADENOSINE-MONOPHOSPHATE SIGNAL GENERATION SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID FRTL-5 THYROID-CELLS; CYCLIC-AMP; IODIDE EFFLUX; HORMONE RECEPTOR; ADENYLYL CYCLASE; NOREPINEPHRINE; ACCUMULATION; CASCADES; GROWTH; CAMP AB TSH and immunoglobulin G (IgG) preparations from patients with Graves' disease increase inositol phosphate as well as cAMP formation in Cos-7 cells transfected with rat TSH receptor (TSHR) cDNA. In a previous report, we mutated alanine 623 of the third cytoplasmic loop (residues 605-625) of the TSHR and showed it was critical for TSH and Graves' IgG initiation of phosphatidylinositol bisphosphate (PIP2) but not cAMP signaling. In this report, we substituted residues in the third loop of the TSHR with sequences from the N- and C-termini of the third loop of the alpha1- and beta2-adrenergic receptors (ARs), which computer analysis has identified as homologous to those in the TSHR. Alanine 623 is conserved in most ARs as well as in glycoprotein hormone receptors; there is, therefore, no change in alanine 623. After transfection of the mutant TSHR cDNAs into Cos-7 cells, we show that the mutant proteins are normally synthesized, processed, and incorporated into the membrane bilayer by Western blotting with a specific receptor antibody. We also show that the dissociation constant for TSH binding in all mutants is the same or lower than wild type TSHR. We then evaluated the ability of TSH or Graves' IgG to increase PIP2 and cAMP signals in each transfectant. Mutants A622 and B621 replace, respectively, residues 622-625 and 621-625 of the TSHR with alpha1- and beta2-AR residues from the C-terminus of the third cytoplasmic loop; mutants A607 and 8605 replace, respectively, TSHR residues 607-609 and 605-609 with N-terminus residues from alpha1- and beta2-AR. All four mutants, like the alanine 623 mutant, result in transfected cells which lose TSH and Graves' IgG initiation Of PIP2 but not cAMP signalling. Like the alanine 623 mutation to glutamic acid, the A607, B605, A622, and B621 mutants also result in decreased basal cAMP, but not inositol phosphate levels, relative to wild type receptor. In contrast to these results, mutants A610, B610, A617, and B617, which replace residues 610-613 or 617-620 of the TSHR with corresponding residues of the alpha1- and beta2-AR, retain TSH and Graves' IgG responsiveness in both inositol phosphate and cAMP assays. Mutation of residues 610-613, in fact, potentiates TSH-increased inositol phosphate production, despite having no effect on TSH-increased cAMP production. Mutation of residues 617-620 markedly elevates basal cAMP levels by comparison to wild type TSHR or pSG5 transfectants and causes a parallel, but smaller, increase in basal inositol phosphate production. This is the first description of a constitutively activated glycoprotein hormone receptor. In sum, the data indicate that the N- and C-terminal five residues of the third cytoplasmic loop of the TSHR, not only alanine 623, are important for TSH and Graves' IgG induction of the PIP2, but not their induction of the cAMP signal. In addition, they are important for the regulation of constitutive cAMP levels, but have only minimal effects on constitutive inositol phosphate levels. Substitution of native residues 617-620 appears to allow receptor activation of the cAMP signaling pathway in the absence of agonist; substitution of native residues 610-613 potentiates agonist-induced PIP2 but not cAMP signaling. Sequence homologies suggest these observations are applicable to gonadotropin receptors as well as all species of TSHR. C1 NIDDKD, MOLEC PATHOPHYSIOL BRANCH, BETHESDA, MD 20892 USA. NIDDKD, CELL REGULAT SECT, BIOCHEM & METAB LAB, BETHESDA, MD 20892 USA. NR 47 TC 79 Z9 82 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD AUG PY 1993 VL 7 IS 8 BP 1009 EP 1020 DI 10.1210/me.7.8.1009 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LV205 UT WOS:A1993LV20500008 PM 7901757 ER PT J AU FUSCHIOTTI, P HARINDRANATH, N MAGE, RG MCCORMACK, WT DHANARAJAN, P ROUX, KH AF FUSCHIOTTI, P HARINDRANATH, N MAGE, RG MCCORMACK, WT DHANARAJAN, P ROUX, KH TI RECOMBINATION ACTIVATING GENES-1 AND GENES-2 OF THE RABBIT - CLONING AND CHARACTERIZATION OF GERMLINE AND EXPRESSED GENES SO MOLECULAR IMMUNOLOGY LA English DT Article ID V(D)J RECOMBINATION; B-CELL; IMMUNOGLOBULIN GENES; RAR-ALPHA; CONVERSION; SEQUENCES; RAG-2; REARRANGEMENT; DIVERSITY; REGION AB The recombination activating genes RAG-1 and RAG-2 appear to be necessary components of the machinery needed for the Ig or TCR gene rearrangements that occur in developing B and T lymphocytes. In addition RAG-2 has been implicated in the process of V-gene diversification by somatic gene conversion in the chicken. Because gene conversion may be an important mechanism for V-gene diversification in the rabbit, we cloned the rabbit RAG locus and characterized the coding regions of the genomic RAG-1 and RAG-2. In addition, we sequenced cDNAs encompassing the RAG-2 coding region, part of the RAG-2 5' untranslated region and a 967 bp fragment of cDNA from the RAG-1 coding region. Northern analysis revealed a RAG-1 mRNA of 6.6 kb which is similar in size to the RAG-1 mRNA reported previously for other species, and a major species of RAG-2 mRNA of 4.4 kb, which is larger than that from the mouse (2.2 kb). Analysis of the genomic clones showed that, as in other species, the RAG-1 and RAG-2 genes are oriented so as to be convergently transcribed. The DNA sequence analysis showed that the rabbit RAG-1 coding region is 91, 85 and 72% identical to human, mouse and chicken, respectively. The deduced RAG-1 protein sequence for rabbit is 93, 90 and 78% identical to human, mouse and chicken. Comparison of the rabbit RAG-2 coding region revealed 90, 87 and 71% identity to human, mouse and chicken, respectively, at the nucleotide level, and 91, 90 and 72% at the protein level. Although there is considerable conservation of sequence between species, we obtained evidence for allelic forms of the rabbit RAG locus both by Southern analyses and by sequencing. A remarkable degree of polymorphism was found in our rabbit colonies, particularly in the region 3' of the rabbit RAG-2 coding region. A 5' cDNA probe hybridized with one or more additional fragments that are not detected with the coding region probes, suggesting that the 5' cDNA sequence results from splicing of one or more upstream exons. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. NIDR,ORAL MED LAB,BETHESDA,MD 20892. UNIV FLORIDA,COLL MED,DEPT PATHOL & LAB MED,GAINESVILLE,FL 32610. FLORIDA STATE UNIV,DEPT BIOL SCI,TALLAHASSEE,FL 32306. FU NIAID NIH HHS [NIAID, AI16596] NR 38 TC 24 Z9 26 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD AUG PY 1993 VL 30 IS 11 BP 1021 EP 1032 DI 10.1016/0161-5890(93)90127-W PG 12 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA LT928 UT WOS:A1993LT92800007 PM 8350872 ER PT J AU KOCSIS, E TRUS, BL STEVEN, AC SMITH, PR HANNAH, JH BRENNAN, MJ KESSEL, M AF KOCSIS, E TRUS, BL STEVEN, AC SMITH, PR HANNAH, JH BRENNAN, MJ KESSEL, M TI ORIENTATION OF PORIN CHANNELS IN THE OUTER-MEMBRANE OF BORDETELLA-PERTUSSIS SO MOLECULAR MICROBIOLOGY LA English DT Review ID ESCHERICHIA-COLI; 3-DIMENSIONAL RECONSTRUCTION; ELECTRON-MICROGRAPHS; PROTEIN PHOE; RESOLUTION; TOPOLOGY; MICROSCOPY; PARTICLES; GENE; OMPC AB We have examined the surface topography and channel connectivity, of a naturally crystalline porin that is known to be functional, and whose structure has not been perturbed by detergent extraction. A three-dimensional density map, calculated from two independent tilt series of negatively stained cell envelopes, reveals three separate channels per trimer on one side (the 'smooth' side), and a single common opening at the other ('rough') side. This arrangement is consistent with the molecular structures recently determined at high resolution by X-ray crystallography for three other porins after detergent solubilization, and implies that the Bordetella pertussis porin may have the same kind of folding. Surface relief maps calculated from electron micrographs of cell envelopes contrasted by unidirectional shadowing clearly show that the side with single opening (i.e. the rough side) represents the external surface. C1 NATL INST ARTHRIT MUSCULOSKELETAL & SKIN DIS,STRUCT BIOL LAB,BETHESDA,MD 20892. US FDA,DIV BACTERIAL PROD,BETHESDA,MD 20892. NYU,SCH MED,DEPT CELL BIOL,NEW YORK,NY 10016. UNIV MARYLAND,DEPT MICROBIOL,COLL PK,MD 20742. HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT MEMBRANE & ULTRASTRUCT RES,IL-91010 JERUSALEM,ISRAEL. NIH,DIV COMP RES & TECHNOL,COMP SYST LAB,BETHESDA,MD 20892. NR 41 TC 9 Z9 9 U1 2 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD AUG PY 1993 VL 9 IS 3 BP 469 EP 476 DI 10.1111/j.1365-2958.1993.tb01708.x PG 8 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA LQ843 UT WOS:A1993LQ84300008 PM 8412696 ER PT J AU KAZANIETZ, MG ARECES, LB BAHADOR, A MISCHAK, H GOODNIGHT, J MUSHINSKI, JF BLUMBERG, PM AF KAZANIETZ, MG ARECES, LB BAHADOR, A MISCHAK, H GOODNIGHT, J MUSHINSKI, JF BLUMBERG, PM TI CHARACTERIZATION OF LIGAND AND SUBSTRATE-SPECIFICITY FOR THE CALCIUM-DEPENDENT AND CALCIUM-INDEPENDENT PROTEIN-KINASE-C ISOZYMES SO MOLECULAR PHARMACOLOGY LA English DT Article ID PHORBOL ESTER PHARMACOPHORE; CD-1 MOUSE SKIN; 12,13-DIBUTYRATE BINDING; TUMOR PROMOTERS; INSECT CELLS; PKC-EPSILON; EXPRESSION; DELTA; BACULOVIRUS; ACTIVATORS AB Analysis of [H-3]phorbol-12,13-dibutyrate (PDBu) binding was performed with protein kinase C (PKC)-alpha, -beta1, -gamma, -delta, -epsilon, -eta, and -zeta produced in Sf9 insect cells using the baculovirus expression system. With the exception of PKC-zeta, all of the PKC isozymes bound [H-3]PDBu with high affinity (K(d) < 1 nm), either in the presence or in the absence of calcium. Scatchard analysis using 1 00% phosphatidylserine vesicles revealed slightly lower affinity for the calcium-independent isozymes (PKC-delta, -epsilon, and -eta) than for the calcium-dependent isozymes (PKC-alpha, -beta, and -gamma). Competition for [H-3]PDBu binding by different classes of PKC activators showed that 12-deoxyphorbol esters, mezerein, and octahydromezerein likewise possessed lower affinity for the calcium-independent isozymes. The mezerein analog thymeleatoxin was the most marked example, being almost 20-fold less potent for binding to PKC-epsilon and -eta than to PKC-beta1. In contrast, the indole alkaloids (-)-indolactam V and (-)-octylindolactam V and the postulated endogenous activator 1,2-diacylglycerol bound with similar affinities to all of the PKC isoforms, suggesting that different residues/configurations in the binding sites of the different PKC isozymes might be involved in interaction with the pharmacophore of the activators. The seven PKC isozymes also showed clearly different substrate specificities with exogenous peptide and protein substrates. The heterogeneous behavior of the different members of the PKC family with ligands and substrates may contribute to the heterogeneity of PKC-mediated pathways at the cellular level. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NCI,GENET LAB,MOLEC GENET SECT,BETHESDA,MD 20892. RI Mischak, Harald/E-8685-2011 NR 46 TC 317 Z9 317 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD AUG PY 1993 VL 44 IS 2 BP 298 EP 307 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LU094 UT WOS:A1993LU09400011 PM 8355667 ER PT J AU RAYNOR, K OCARROLL, AM KONG, HY YASUDA, K MAHAN, LC BELL, GI REISINE, T AF RAYNOR, K OCARROLL, AM KONG, HY YASUDA, K MAHAN, LC BELL, GI REISINE, T TI CHARACTERIZATION OF CLONED SOMATOSTATIN RECEPTORS SSTR4 AND SSTR5 SO MOLECULAR PHARMACOLOGY LA English DT Article ID RAT NEOCORTICAL NEURONS; BRAIN SOMATOSTATIN; MOLECULAR-CLONING; EXPRESSION; BINDING; ANALOGS; SUBTYPES; RELEASE; INHIBITION; SECRETION AB The recent molecular cloning of the genes and cDNAs encoding multiple somatostatin (SRIF) receptor subtypes has allowed for the individual expression of these receptors in mammalian cells and characterization of their respective pharmacological profiles. Previously, we fully described and compared the pharmacological properties of the first three SRIF receptor subtypes, SRIF receptor type (SSTR)1, SSTR2, and SSTR3. In the present study, we have investigated the properties of the newly cloned SRIF receptor subtypes SSTR4 and SSTR5 with regard to pharmacological profiles, the regulation of high affinity agonist binding to these receptors by stable GTP analogues, Na+, or prior exposure to agonists, and the inhibition of forskolin-stimulated cAMP accumulation mediated by these receptors. We labeled SSTR4 and SSTR5 expressed in Chinese hamster ovary (CHO-K1) and COS-1 cells, respectively, with the metabolically stable SRIF analogue I-125-CGP 23996. Radioligand binding competition studies were performed using SRIF analogues of differing structures, including hexapeptide analogues similar to MK-678, octapeptide analogues similar to SMS 201-995, pentapeptide analogues similar to c[Ahep-Phe-D-Trp-Lys-Thr(Bzl)], and linear SRIF analogues. SSTR4 bound compounds in all structural classes with high to moderate affinities, and several compounds were identified that are >100-fold selective for SSTR4, compared with the other cloned SRIF receptors, including the linear SRIF analogue BIM-23052 and the CGP 23996-like SRIF analogue L-362,855. In contrast, SSTR5 bound very few SRIF analogues with high affinity. Both receptors could be regulated by prior exposure to agonist. In addition, agonist binding to SSTR4 was reduced by stable GTP analogues, Na+, and pertussis toxin, but agonist binding to SSTR5 was not affected by these treatments. SSTR4 is efficiently coupled to the inhibition of adenylyl cyclase activity, whereas SSTR5 appears not to couple to this cellular effector system. Such differences between the cloned SRIF receptors provide useful strategies for identifying regions of these receptor subtypes that may be involved in ligand-binding specificities and G protein and cellular effector system coupling. The identification of subtype-selective SRIF analogues may lead to more specific therapeutic interventions. C1 UNIV PENN,SCH MED,DEPT PHARMACOL,103 JOHN MORGAN BLDG,36TH & HAMILTON WALK,PHILADELPHIA,PA 19104. UNIV CHICAGO,DEPT BIOCHEM & MOLEC BIOL,CHICAGO,IL 60637. UNIV CHICAGO,DEPT MED,CHICAGO,IL 60637. UNIV CHICAGO,HOWARD HUGHES MED INST,CHICAGO,IL 60637. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. FU NIMH NIH HHS [MH45533, MH48518] NR 46 TC 193 Z9 196 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD AUG PY 1993 VL 44 IS 2 BP 385 EP 392 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LU094 UT WOS:A1993LU09400022 PM 8102785 ER PT J AU LEROITH, D KAVSAN, VM KOVAL, AP ROBERTS, CT AF LEROITH, D KAVSAN, VM KOVAL, AP ROBERTS, CT TI PHYLOGENY OF THE INSULIN-LIKE GROWTH-FACTORS (IGFS) AND RECEPTORS - A MOLECULAR APPROACH SO MOLECULAR REPRODUCTION AND DEVELOPMENT LA English DT Article DE GROWTH HORMONES; TYROSINE KINASE; GENE REGULATION; RECEPTORS ID FACTOR-I GENE; NUCLEOTIDE-SEQUENCE; FUNCTIONAL-ANALYSIS; PROMOTER REGION; LEADER EXONS; FACTOR CDNA; CLONING; SUPERFAMILY; EXPRESSION; EVOLUTION AB The IGFs (IGF-I and IGF-II) are essential for normal mammalian growth and development. Their actions are mediated primarily by their interactions with the type I IGF receptor (IGF-I receptor), a transmembrane tyrosine kinase. The ligands and the IGF-I receptor are structurally related to insulin and to the insulin receptor, respectively. Analysis of evolutionary conservation has often provided insights into essential regions of molecules such as hormones and their receptors. The genes for insulin and IGFs have been partially characterized in a number of vertebrate species extending evolutionarily from humans as far back as fish. The sequences of the exons encoding the mature insulin and IGF peptides are highly conserved among vertebrate species, and IGF-I-like molecules are found in species whose origins extend back as much as 550 million years. The insulin receptor is also highly conserved in vertebrate species, and an insulin-receptor-like molecule has been characterized in Drosophila. In contrast, IGF-I receptors have only been characterized in mammalian species and partially studied in Xenopus, in which the tyrosine kinase domain is highly conserved. Studies are presently being undertaken to analyze in more detail the regulation of the genes encoding this important family of growth factors and the structure/function relationships in the gene products themselves. (C) 1993 Wiley-Liss, Inc.* C1 UKRAINIAN ACAD SCI,INST MOLEC BIOL & GENET,DEPT BIOSYNTH NUCLEIC ACIDS,KIEV,UKRAINE. RP LEROITH, D (reprint author), NIDDK,DIABET BRANCH,MOLEC & CELLULAR PHYSIOL SECT,BLDG 10,ROOM 8 S239,BETHESDA,MD 20892, USA. OI Roberts, Charles/0000-0003-1756-5772 NR 29 TC 33 Z9 33 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1040-452X J9 MOL REPROD DEV JI Mol. Reprod. Dev. PD AUG PY 1993 VL 35 IS 4 BP 332 EP 338 DI 10.1002/mrd.1080350403 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA LP881 UT WOS:A1993LP88100002 PM 8398110 ER PT J AU NISSLEY, P KIESS, W SKLAR, M AF NISSLEY, P KIESS, W SKLAR, M TI DEVELOPMENTAL EXPRESSION OF THE IGF-II/MANNOSE 6-PHOSPHATE RECEPTOR SO MOLECULAR REPRODUCTION AND DEVELOPMENT LA English DT Article DE LYSOSOMAL ENZYMES; BETA-GALACTOSIDASE; IGF-II/M6P RECEPTOR ID GROWTH-FACTOR-II; MANNOSE 6-PHOSPHATE; MANNOSE-6-PHOSPHATE RECEPTOR; BETA-GALACTOSIDASE; BINDING-SITES; RAT SERUM; CELLS; AFFINITY; CHICKEN; LIGAND AB The first indication that the insulin-like growth factor-11/mannose 6-phosphate receptor (IGF-II/M6PR) is developmentally regulated came from studies of the serum form of the receptor in the rat. By immunoblotting, the circulating form of the receptor, which was 10 kDa smaller than the tissue receptor, was high in 19 day fetal and 3, 10, and 20 day postnatal sera and then declined sharply. We next used quantitative immunoblotting to measure the total tissue IGF-II/M6PR in the rat. The receptor levels were high in fetal tissues and in most tissues declined dramatically in late gestation and/or in the early postnatal period. The rank order of receptor expression was heart > placenta > lung = intestine > muscle = kidney > liver > brain. In heart, the receptor was 1.7% of total protein in the extract. More recently, we have examined the expression of IGF-II/M6PR mRNA using Northern blotting and a solution hybridization/RNase protection assay. The rank order of receptor mRNA concentration among fetal tissues agreed with the rank order of receptor protein. The concentration of receptor mRNA was significantly lower in postnatal tissue than in fetal tissue. Thus IGF-II/M6PR mRNA concentration is an important determinant of receptor protein in most tissues. What is the function of the IGF-II/M6PR in embryonic and fetal tissues? The M6PR in birds and frogs does not bind IGF-II. It is intriguing that the rat IGF-II/M6PR is prominent during the embryonic and fetal periods, times at which the differences between mammals, on the one hand, and frogs and birds, on the other, are most striking. Tissue remodeling is an important feature of embryonic and fetal development. Therefore, the well-established lysosomal enzyme targeting function of the receptor may be of particular importance. Since IGF-II can inhibit the cellular uptake of lysosomal enzymes via the IGF-II/M6PR, IGF-II may modulate this lysosomal enzyme targeting function. In addition, the receptor can provide a degradative pathway for IGF-II by receptor-mediated internalization. Thus the receptor could provide a check on the high levels of IGF-II known to be present in the fetus. Finally, the IGF-II/M6PR could directly signal certain biologic responses to IGF-II. (C) 1993 Wiley-Liss, Inc.* C1 UNIV MUNICH,CHILDRENS HOSP,W-8000 MUNICH 2,GERMANY. GEORGETOWN UNIV,SCH MED,DEPT ENDOCRINOL,WASHINGTON,DC 20057. RP NISSLEY, P (reprint author), NCI,METAB BRANCH,BLDG 10,RM 4N115,BETHESDA,MD 20892, USA. NR 38 TC 45 Z9 45 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 1040-452X J9 MOL REPROD DEV JI Mol. Reprod. Dev. PD AUG PY 1993 VL 35 IS 4 BP 408 EP 413 DI 10.1002/mrd.1080350415 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA LP881 UT WOS:A1993LP88100014 PM 8398120 ER PT J AU STOPPER, H KORBER, C SCHIFFMANN, D CASPARY, WJ AF STOPPER, H KORBER, C SCHIFFMANN, D CASPARY, WJ TI CELL-CYCLE DEPENDENT MICRONUCLEUS FORMATION AND MITOTIC DISTURBANCES INDUCED BY 5-AZACYTIDINE IN MAMMALIAN-CELLS SO MUTATION RESEARCH LA English DT Article DE MICRONUCLEI; L5178Y CELLS; 5-AZACYTIDINE; BERENIL; DES; ETHIONINE; MITOSIS ID SISTER-CHROMATID EXCHANGES; MOUSE LYMPHOMA-CELLS; DNA METHYLATION; CHROMOSOME; HETEROCHROMATIN; MUTAGENICITY; INDUCTION; ANALOGS; PROTEIN; CPGS AB 5-Azacytidine was originally developed to treat human myelogenous leukemia. However, interest in this compound has expanded because of reports of its ability to affect cell differentiation and to alter eukaryotic gene expression. In an ongoing attempt to understand the biochemical effects of this compound, we examined the effects of 5-azacytidine on mitosis and on micronucleus formation in mammalian cells. In L5178Y mouse cells, 5-azacytidine induced micronuclei at concentrations at which we and others have already reported its mutagenicity at the tk locus. Using CREST staining and C-banding studies, we showed that the induced micronuclei contained mostly chromosomal fragments although some may have containedwhole chromosomes. By incorporating BrdU into the DNA of SHE cells, we determined that micronuclei were induced only when the compound was added while the cells were in S phase. Microscopically visible effects due to 5-azacytidine treatment were not observed until anaphase of the mitosis following treatment or thereafter. 5-Azacytidine did not induce micronuclei via interference with formation of the metaphase chromosome arrangement in mitosis, a common mechanism leading to aneuploidy. Supravital UV microscopy revealed that chromatid bridges were observed in anaphase and, in some cases, were sustained into interphase. In the first mitosis after 5-azacytidine treatment we observed that many cells were unable to perform anaphase separation. All of these observations indicate that 5-azacytidine is predominantly a clastogen through its incorporation into DNA. C1 NIEHS,CANC & MOLEC GENET GRP,POB 12233,RES TRIANGLE PK,NC 27709. UNIV WURZBURG,INST PHARMACOL & TOXICOL,W-8700 WURZBURG,GERMANY. NR 40 TC 30 Z9 31 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD AUG PY 1993 VL 300 IS 3-4 BP 165 EP 177 DI 10.1016/0165-1218(93)90048-I PG 13 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA LN814 UT WOS:A1993LN81400004 PM 7687016 ER PT J AU PARSHAD, R TARONE, RE PRICE, FM SANFORD, KK AF PARSHAD, R TARONE, RE PRICE, FM SANFORD, KK TI CYTOGENETIC EVIDENCE FOR DIFFERENCES IN DNA INCISION ACTIVITY IN XERODERMA-PIGMENTOSUM GROUP A-CELLS, C-CELLS AND D-CELLS AFTER X-IRRADIATION DURING G(2)-PHASE SO MUTATION RESEARCH LA English DT Article DE XERODERMA-PIGMENTOSUM; X-IRRADIATION; HUMAN FIBROBLASTS; LYMPHOCYTES; 1-BETA-D-ARABINOFURANOSYLCYTOSINE; CHROMATID BREAKS; CHROMATID GAPS; INCISION ACTIVITY ID COMPLEMENTATION GROUPS; CYTOSINE-ARABINOSIDE; TUMOR-CELLS; REPAIR; DAMAGE; CANCER; RADIOSENSITIVITY; FIBROBLASTS; INDIVIDUALS; SITES AB The capacity of cells to incise DNA to remove altered sites after DNA damage can be determined from the rate of DNA-strand break accumulation in the presence of an inhibitor of DNA-repair synthesis, such as 1-beta-D-arabinofuranosylcytosine (ara-C). Because each chromatid contains a single continuous molecule of double-stranded DNA, chromatid breaks and gaps, i.e., non-displaced breaks, represent unrepaired DNA-strand breaks. The accumulation of chromatid breaks and gaps after X-irradiation in the presence of ara-C thus provides a measure of DNA incision activity. Addition of ara-C to skin fibroblasts or stimulated blood lymphocytes from normal individuals at intervals after X-irradiation significantly increased frequencies of chromatid breaks and/or gaps. In contrast, addition of ara-C to XP cells of complementation groups A and D had a negligible effect and a significant but less than normal effect on XP cells of complementation group C and one sample of blood lymphocytes of undetermined complementation group. The results thus show negligible incision activity after G2 phase X-irradiation in XP-A and XP-D cells and a level higher but less than normal in XP-C cells. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. HOWARD UNIV,COLL MED,DEPT PATHOL,WASHINGTON,DC 20059. NR 31 TC 20 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD AUG PY 1993 VL 294 IS 2 BP 149 EP 155 DI 10.1016/0921-8777(93)90023-A PG 7 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA LK608 UT WOS:A1993LK60800007 PM 7687007 ER PT J AU BURKHART, JG BURKHART, BA SAMPSON, KS MALLING, HV AF BURKHART, JG BURKHART, BA SAMPSON, KS MALLING, HV TI ENU-INDUCED MUTAGENESIS AT A SINGLE-A - T-BASE PAIR IN TRANSGENIC MICE CONTAINING PHI-X174 SO MUTATION RESEARCH LA English DT Article DE PHI-X174; TRANSGENIC MICE; ENU-INDUCED MUTAGENESIS; N-ETHYL-N-NITROSOUREA ID ETHYL-N-NITROSOUREA; ESCHERICHIA-COLI; DNA-REPAIR; SHUTTLE VECTOR; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; SEQUENCE SPECIFICITY; INDUCED MUTATIONS; MAMMALIAN-CELLS; LOCUS MUTATIONS; HOST STRAIN AB Transgenic mice containing the bacteriophage phiX174 am3 as a chromosomally integrated and recoverable marker for in vivo mutation have been produced to measure spontaneous and induced substitutions at an A:T base pair among single copies. PhiX174 was chosen for its small size (5 kb), unique sequence, and the opportunity to take advantage of previously reported in vitro data on mutation and repair; the am3 site provides sequence specificity in a reversion assay for mutation of an A:T base pair. Inbred C57Bl/6 mice have been made homozygous for approximately 100 copies of the the phage sequence without any apparent detrimental effects on the homozygous individuals. Recoveries of phage from mouse tissues are in the range of 1-5 X 10(7) PFU per mug mouse DNA; both recovery and mutation are independent of endogenous CpG methylation. Background mutation frequencies are 2-4 X 10(-7) among phage recovered from liver, brain, spleen, and kidney. Adult mice were treated with 200 mg/kg N-ethyl-N-nitrosourea, and phage were recovered at 2 and 14 days after treatment. At 2 days after treatment we observed a slight increase only among phage isolated from the brain of one mouse out of four. At 14 days after ENU treatment, there were significant increases in mutation frequencies among phage recovered from the liver (6 X) and spleen (10 X). These results demonstrate (1) response of a single A:T base pair to alkylation-induced mutation in a nonexpressed gene, (2) the role of cell proliferation in somatic mutagenesis, and (3) provide a model for a transgenic approach for study of site-specific mutagenesis in vivo in higher eukaryotes. C1 NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. RP BURKHART, JG (reprint author), NIEHS,GENET LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 61 TC 45 Z9 45 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD AUG PY 1993 VL 292 IS 1 BP 69 EP 81 DI 10.1016/0165-1161(93)90009-O PG 13 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA LP723 UT WOS:A1993LP72300007 PM 7688099 ER PT J AU BOGUSKI, MS LOWE, TMJ TOLSTOSHEV, CM AF BOGUSKI, MS LOWE, TMJ TOLSTOSHEV, CM TI DBEST - DATABASE FOR EXPRESSED SEQUENCE TAGS SO NATURE GENETICS LA English DT Letter ID CAENORHABDITIS-ELEGANS RP BOGUSKI, MS (reprint author), NIH,NATL LIB HLTH,NATL CTR BIOTECHNOL INFORMAT,BLDG 38A,ROOM 8N805,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 15 TC 1009 Z9 1034 U1 2 U2 11 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD AUG PY 1993 VL 4 IS 4 BP 332 EP 333 DI 10.1038/ng0893-332 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA LQ178 UT WOS:A1993LQ17800007 PM 8401577 ER PT J AU POLYMEROPOULOS, MH XIAO, H SIKELA, JM ADAMS, M VENTER, JC MERRIL, CR AF POLYMEROPOULOS, MH XIAO, H SIKELA, JM ADAMS, M VENTER, JC MERRIL, CR TI CHROMOSOMAL DISTRIBUTION OF 320 GENES FROM A BRAIN CDNA LIBRARY SO NATURE GENETICS LA English DT Article ID HUMAN GENOME; ASSIGNMENT; MAP AB We have determined the chromosomal assignment of 320 brain expressed genes by studying the segregation of polymerase chain reaction (PCR) products in human rodent somatic cell hybrids and by genetically mapping polymorphic cDNAs using the CEPH (Centre d'Etude du Polymophisme Humaine) reference pedigrees and database. These mapped genes can function as markers on the physical map of the human genome, as well as serve as candidate disease gene loci. Distribution of these genes to the human chromosomes correlates well with the GC content of the chromosomes. However, the distribution of these genes does not correlate well with the cytogenetic length of each chromosome. C1 UNIV COLORADO,HLTH SCI CTR,DENVER,CO 80262. INST GENOM RES,GAITHERSBURG,MD 20878. RP POLYMEROPOULOS, MH (reprint author), NIMH,BIOCHEM GENET LAB,CTR NEUROSCI,WASHINGTON,DC 20032, USA. NR 19 TC 83 Z9 83 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD AUG PY 1993 VL 4 IS 4 BP 381 EP 386 DI 10.1038/ng0893-381 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA LQ178 UT WOS:A1993LQ17800016 PM 8401586 ER PT J AU DIMARTINO, A SAFAR, J CALLEGARO, L SALEM, N GIBBS, CJ AF DIMARTINO, A SAFAR, J CALLEGARO, L SALEM, N GIBBS, CJ TI GANGLIOSIDE COMPOSITION CHANGES IN SPONGIFORM ENCEPHALOPATHIES - ANALYSES OF 263K SCRAPIE-INFECTED HAMSTER BRAINS SO NEUROCHEMICAL RESEARCH LA English DT Article DE GANGLIOSIDES; ALKALI-LABILE GANGLIOSIDES; SPONGIFORM ENCEPHALOPATHY; SCRAPIE; FATTY ACIDS ID PRECURSOR PROTEIN; PURIFICATION AB Ganglioside composition in brains of terminally ill LVG/LAK golden Syrian hamsters infected with the 263K strain of the scrapie agent was analyzed. Results were compared to those obtained from noninfected animals matched by age, sex, and strain. Gangliosides extracted from scrapie-infected animals showed little change in major components, while an increased number of new alkali-labile species appeared. Additionally, the animal strain employed demonstrated a significant polymorphism in brain ganglioside composition. No significant changes in incubation time, clinical development or pathologic features of scrapie were associated with this polymorphism. C1 NIH,CNS STUDIES LAB,9000 ROCKVILLE PIKE,BLDG 36-4A15,BETHESDA,MD 20892. FIDIA RES LABS,DIV ADV TECHNOL,ABANO TERME,ITALY. NIAAA,DICBR,MEMBRANE BIOCHEM & BIOPHYS LAB,ROCKVILLE,MD 20852. RI Safar, Jiri/G-6512-2013 NR 24 TC 3 Z9 3 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD AUG PY 1993 VL 18 IS 8 BP 907 EP 913 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA LN214 UT WOS:A1993LN21400008 PM 8371832 ER PT J AU PACAK, K PALKOVITS, M KVETNANSKY, R KOPIN, IJ GOLDSTEIN, DS AF PACAK, K PALKOVITS, M KVETNANSKY, R KOPIN, IJ GOLDSTEIN, DS TI STRESS-INDUCED NOREPINEPHRINE RELEASE IN THE PARAVENTRICULAR NUCLEUS OF RATS WITH BRAIN-STEM HEMISECTIONS - A MICRODIALYSIS STUDY SO NEUROENDOCRINOLOGY LA English DT Article DE DIHYDROXYPHENYLGLYCOL; DIHYDROXYPHENYLACETIC ACID; IMMOBILIZATION STRESS; CORTICOSTERONE ID VENTRAL NORADRENERGIC BUNDLE; DOPAMINE-BETA-HYDROXYLASE; TYROSINE-HYDROXYLASE; SUPRAOPTIC NUCLEI; HYPOTHALAMUS; CATECHOLAMINES; PATHWAYS; NEURONS; ORGANIZATION; INNERVATION AB Immobilization (IMMO) of conscious rats evokes marked increases in release of norepinephrine (NE) in the paraventricular nucleus (PVN) of the hypothalamus, consistent with a role of NE in the PVN release of corticotropin-releasing hormone and therefore in pituitary-adrenocortical activation during stress. The present study examined the effects of surgical hemisection of the brainstem between the locus ceruleus and rostral portion of the medulla on release of NE in the PVN of the hypothalamus in vivo in conscious rats, at baseline and during IMMO. Concentrations of NE, the intraneuronal NE metabolite dihydroxyphenylglycol (DHPG), and the dopamine metabolite dihydroxyphenylacetic acid (DOPAC) were measured in microdialysate samples obtained beginning 24 h after implantation of a microdialysis probe in the PVN either ipsilateral or contralateral to the hemisection. On the lesioned side, baseline levels of NE, DHPG, and DOPAC were significantly lower and IMMO-induced increases were smaller than in sham-operated rats. Contralateral to the hemisection, DOPAC levels were significantly reduced. Neither baseline levels nor IMMO-induced increases in plasma corticosterone levels differed between lesioned and sham-operated animals. The present results indicate that: (1) NE release in the PVN at baseline and during IMMO depends mainly on ascending medullary tracts from ipsilateral brainstem A1 and A2 catecholaminergic areas, with small contributions from the locus ceruleus and from contralateral medullary cells, and (2) brainstem hemisection does not influence IMMO-induced activation of the hypothalamic-pituitary-adrenocortical axis as indicated by plasma corticosterone levels in conscious rats. C1 NINCDS,CLIN NEUROSCI BRANCH,BLDG 10,ROOM 5N262,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 NR 35 TC 64 Z9 64 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD AUG PY 1993 VL 58 IS 2 BP 196 EP 201 DI 10.1159/000126533 PG 6 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA MB151 UT WOS:A1993MB15100007 PM 8264865 ER PT J AU APPOLLONIO, IM GRAFMAN, J SCHWARTZ, V MASSAQUOI, S HALLETT, M AF APPOLLONIO, IM GRAFMAN, J SCHWARTZ, V MASSAQUOI, S HALLETT, M TI MEMORY IN PATIENTS WITH CEREBELLAR DEGENERATION SO NEUROLOGY LA English DT Article ID INHERITED OLIVOPONTOCEREBELLAR ATROPHY; INFORMATION-PROCESSING SPEED; PARKINSONS-DISEASE; FRIEDREICHS ATAXIA; MENTAL SKILLS; ALZHEIMERS; DYSFUNCTION; IMPLICIT; LESIONS AB Eleven patients with relatively selective cerebellar degeneration and 11 normal control subjects underwent a comprehensive neurologic an neuropsychological examination. The neuropsychological tests assessed general intellectual ability, different aspects of memory (effortful, automatic, and implicit memory processes), speed of information processing, and verbal fluency (using both category and letter fluency tasks). The results indicated that cerebellar patients were significantly impaired only on tasks requiring the use of executive functions, such as the initiation/perseveration subtest of the Mattis Dementia Rating Scale or the fluency tests, and on memory measures requiring greater processing effort. They performed normally on automatic and implicit measures of memory. Performance on the effortful memory and executive measures was not associated with neurologic variables or mood state. After controlling for the initiation/perseveration deficit, the effortful memory scores of the cerebellar patients were no longer different from those of controls. The present study suggests that memory in patients with relatively pure cerebellar dysfunction is only partially compromised and that the impairment is secondary to a deficit in executive functions. C1 NINCDS,COGNIT NEUROSCI SECT,MED NEUROL BRANCH,BLDG 10,ROOM 55209,BETHESDA,MD 20892. NINCDS,HUMAN MOTOR CONTROL SECT,BETHESDA,MD 20892. UNIV MILAN,S GERARDO HOSP,DEPT NEUROL,MONZA,ITALY. OI Grafman, Jordan H./0000-0001-8645-4457 NR 54 TC 181 Z9 182 U1 2 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG PY 1993 VL 43 IS 8 BP 1536 EP 1544 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA LR500 UT WOS:A1993LR50000017 PM 8351008 ER PT J AU KAPLAN, DR MATSUMOTO, K LUCARELLI, E THIELE, CJ AF KAPLAN, DR MATSUMOTO, K LUCARELLI, E THIELE, CJ TI INDUCTION OF TRKB BY RETINOIC ACID MEDIATES BIOLOGIC RESPONSIVENESS TO BDNF AND DIFFERENTIATION OF HUMAN NEUROBLASTOMA-CELLS SO NEURON LA English DT Article ID HUMAN NEURO-BLASTOMA; NERVE GROWTH-FACTOR; ACUTE PROMYELOCYTIC LEUKEMIA; TYROSINE PROTEIN-KINASE; NEUROTROPHIC FACTOR; BINDING PROTEIN; SPINAL-CORD; PROTOONCOGENE PRODUCT; NGF RESPONSIVENESS; MYC GENE AB Retinoic acid (RA) induces the neuronal differentiation of many human neuroblastoma cell lines. In this study, we show that RA treatment of neuroblastoma cells induces the expression of TrkB, the receptor for the neurotrophins BDNF, NT-3, and NT-415. BDNF addition to RA-treated SH-SY5Y neuroblastoma cells stimulated the tyrosine phosphorylation of TrkB and neuronal differentiation. RA treatment of KCNR neuroblastoma cells, which constitutively express BDNF mRNA, resulted in the expression of TrkB and differentiation in the absence of added BDNF. Finally, in 15N neuroblastoma cells, which express BDNF mRNA but do not differentiate in response to RA, RA induced only a truncated form of TrkB. 15N cells transfected with full-length TrkB differentiated in the absence of RA. These results indicate that RA induces the neuronal differentiation of neuroblastoma cells by modulating the expression of neurotrophin receptors. C1 NCI,PEDIAT BRANCH,CELLULAR & MOLEC BIOL SECT,BETHESDA,MD 20892. RP KAPLAN, DR (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MMCL,EUKARYOT SIGNAL TRANSDUCT GRP,FREDERICK,MD 21702, USA. RI Lucarelli, Enrico/G-3588-2015 OI Lucarelli, Enrico/0000-0002-6681-6374 FU NCI NIH HHS [N01-CO-74101] NR 72 TC 267 Z9 273 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD AUG PY 1993 VL 11 IS 2 BP 321 EP 331 DI 10.1016/0896-6273(93)90187-V PG 11 WC Neurosciences SC Neurosciences & Neurology GA LU065 UT WOS:A1993LU06500011 PM 8394722 ER PT J AU HALBREICH, U BANCROFT, J DENNERSTEIN, L ENDICOTT, J FACCINETTI, F GENAZZANI, A MORSE, C PARRY, B RUBINOW, D REID, R SCHIFF I SMITH, S BACKSTROM, T AF HALBREICH, U BANCROFT, J DENNERSTEIN, L ENDICOTT, J FACCINETTI, F GENAZZANI, A MORSE, C PARRY, B RUBINOW, D REID, R SCHIFF, I SMITH, S BACKSTROM, T TI MENSTRUALLY RELATED DISORDERS - POINTS OF CONSENSUS, DEBATE, AND DISAGREEMENT SO NEUROPSYCHOPHARMACOLOGY LA English DT Editorial Material C1 MED RES CTR COUNCIL, EDINBURGH, SCOTLAND. UNIV MELBOURNE, PARKVILLE, VIC 3052, AUSTRALIA. COLUMBIA UNIV, NEW YORK, NY 10027 USA. UNIV MODENA, I-41100 MODENA, ITALY. UNIV CALIF SAN DIEGO, SAN DIEGO, CA 92103 USA. NIMH, BETHESDA, MD 20892 USA. UNIV KENSINGTON, KENSINGTON, PEI, CANADA. HARVARD UNIV, CAMBRIDGE, MA 02138 USA. SINAI HOSP, BALTIMORE, MD 21215 USA. UNIV UPPSALA, S-75105 UPPSALA, SWEDEN. RP HALBREICH, U (reprint author), SUNY Buffalo, CTR CLIN, 462 GRIDER ST, BUFFALO, NY 14215 USA. NR 0 TC 10 Z9 10 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD AUG PY 1993 VL 9 IS 1 BP 13 EP 15 PG 3 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA LN711 UT WOS:A1993LN71100002 PM 8397720 ER PT J AU GEJMAN, PV MARTINEZ, M CAO, QH FRIEDMAN, E BERRETTINI, WH GOLDIN, LR KOROULAKIS, P AMES, C LERMAN, MA GERSHON, ES AF GEJMAN, PV MARTINEZ, M CAO, QH FRIEDMAN, E BERRETTINI, WH GOLDIN, LR KOROULAKIS, P AMES, C LERMAN, MA GERSHON, ES TI LINKAGE ANALYSIS OF 57 MICROSATELLITE LOCI TO BIPOLAR DISORDER SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE MAPPING; BIPOLAR ILLNESS; MICROSATELLITES; GENETIC LINKAGE SIMULATIONS; GNAS1; HUMAN X-LINKED GABA-A RECEPTOR ALPHA-3-SUBUNIT GENE ID DINUCLEOTIDE REPEAT POLYMORPHISM; SUBUNIT GENE GNAS1; MAP; CHROMOSOME-20; SIMULATION; SEARCH; POWER AB The authors' goal was to screen for genetic linkage with highly informative deoxyribonucleic acid (DNA) microsatellite markers on a series of moderately sized North American bipolar disorder (BP) pedigrees. These BP pedigrees were genotyped with 57 short tandem-repeat polymorphic systems (microsatellites) that were enzymatically amplified from genomic DNA. We did not find significant evidence for genetic linkage. We und isolated LOD scores greater than 2 on chromosome 1 at two loci in individual pedigrees. Simulation studies for multiple analyses under the assumptions of linkage and nonlinkage were performed. The simulations show that LOD scores greater than 2 could be expected even when linkage is absent. Significance levels need to be considered carefully in systematic linkage studies. C1 INSERM, F-75005 PARIS, FRANCE. KAROLINSKA HOSP, DEPT CLIN GENET, S-10401 STOCKHOLM 60, SWEDEN. THOMAS JEFFERSON UNIV, JEFFERSON MED COLL, DEPT PSYCHIAT & HUMAN BEHAV, PHILADELPHIA, PA 19107 USA. RP GEJMAN, PV (reprint author), NIMH, CLIN NEUROGENET BRANCH, 10-3N218, BETHESDA, MD 20892 USA. RI Martinez, Maria/B-3111-2013 OI Martinez, Maria/0000-0003-2180-4537 NR 67 TC 44 Z9 44 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD AUG PY 1993 VL 9 IS 1 BP 31 EP 40 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA LN711 UT WOS:A1993LN71100008 PM 8397721 ER PT J AU LIPSKA, BK JASKIW, GE WEINBERGER, DR AF LIPSKA, BK JASKIW, GE WEINBERGER, DR TI POSTPUBERTAL EMERGENCE OF HYPERRESPONSIVENESS TO STRESS AND TO AMPHETAMINE AFTER NEONATAL EXCITOTOXIC HIPPOCAMPAL DAMAGE - A POTENTIAL ANIMAL-MODEL OF SCHIZOPHRENIA SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE HIPPOCAMPUS; SCHIZOPHRENIA; ANIMAL MODEL; DOPAMINE; LOCOMOTOR ACTIVITY; NEONATAL LESION; IBOTENIC ACID ID MEDIAL PREFRONTAL CORTEX; IBOTENIC ACID LESIONS; NUCLEUS-ACCUMBENS; DOPAMINE RELEASE; ANTEROGRADE TRANSPORT; LOCOMOTOR-ACTIVITY; NEUROLEPTIC DRUGS; RAT; BRAIN; NEURONS AB The constellation of major phenomena associated with schizophrenia (e.g., postpubertal onset, congenital hippocampal area damage, cortical functional deficits, limbic dopamine (DA) dysregulation, and vulnerability to stress) have been difficult to explain with a unitary animal model. Although it has been shown that rats develop increased mesolimbic DA transmission and reduced cortical DA turnover following adult excitotoxic lesions of the ventral hippocampus (VH), the implication of early developmental VH lesions are not known. To determine the developmental sequelae of such changes, we produced ibotenic acid lesions of the ventral hippocampal formation in rats on the 7th day after birth (PD7). Motor activity in a novel environment, after saline injection and after d-amphetamine administration were similar in control and lesioned rats at PD35. However, in early adulthood, at PD56, animals with the hippocampal lesion were hyperactive in each of these conditions. The emergence of the hyperactivity at PD56 could be prevented by pretreatment with haloperidol. Moreover, rats lesioned as neonates, in contrast to a similar lesion induced in adult animals, were also hyperresponsive to stress evaluated with a swim test. This latter effect is analogous to that seen after adult lesions of the medial prefrontal cortex, rather than after adult lesions of VH, suggesting that the neonatal VH lesion may affect functional development of the medial prefrontal cortex. These results demonstrate that in rats with neonatally induced excitotoxic VH lesions, behavioral indices consistent with increased mesolimbic DA responsivity to stressful and to pharmacologic stimuli emerge only in early adulthood. Homologous mechanisms may underlie certain aspects of the pathophysiology of schizophrenia. C1 UNIV HOSP CLEVELAND,DEPT PSYCHIAT,CLEVELAND,OH 44106. RP LIPSKA, BK (reprint author), NIMH,ST ELIZABETHS,CTR NEUROSCI,INTRAMURAL RES PROGRAM,WASHINGTON,DC 20032, USA. RI Lipska, Barbara/E-4569-2017 NR 61 TC 492 Z9 502 U1 0 U2 5 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 AUG PY 1993 VL 9 IS 1 BP 67 EP 75 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA LN711 UT WOS:A1993LN71100012 PM 8397725 ER PT J AU SEGATTO, O PELICCI, G GIULI, S DIGIESI, G DIFIORE, PP MCGLADE, J PAWSON, T PELICCI, PG AF SEGATTO, O PELICCI, G GIULI, S DIGIESI, G DIFIORE, PP MCGLADE, J PAWSON, T PELICCI, PG TI SHC PRODUCTS ARE SUBSTRATES OF ERBB-2 KINASE SO ONCOGENE LA English DT Article ID EPIDERMAL GROWTH-FACTOR; RECEPTOR TYROSINE KINASES; AUTOPHOSPHORYLATION SITES; SIGNAL TRANSDUCTION; PHOSPHOLIPASE-C; EGF RECEPTOR; NEU ONCOGENE; HUMAN-BREAST; PROTEIN; PHOSPHORYLATION AB The shc gene encodes three widely expressed proteins of 46, 52 and 66 kDa. Overexpression of p46shc and p52shc in NIH3T3 fibroblasts induces a tumorigenic phenotype. Shc products are phosphorylated on tyrosine by the activated epidermal growth factor receptor (EGFR) and become physically associated with EGFR via their SH2 domain. Thus Shc oncoproteins may play a role in mitogenic signal transduction. Here we report that Shc products are substrates also of the erbB-2 kinase and form complexes with the erbB-2 product in intact cells. In vitro, the bacterially expressed Shc SH2 domain is sufficient to reconstitute the high affinity Shc/erbB-2 interaction. The erbB-2 region required for Shc binding was narrowed down to the most COOH-terminal 179 residues of gp185erbB-2; within this region, phosphorylation of one or more of the erbB-2 autophosphorylation sites is required for Shc/gp185erbB-2 complex formation as well as optimal phosphorylation of Shc products by the erbB-2 kinase. Thus, Shc proteins may play a role in signal transduction by gp185erbB-2. C1 MT SINAI HOSP, SAMUEL LUNENFELD RES INST, DIV MOLEC & DEV BIOL, TORONTO M5G 1X5, ONTARIO, CANADA. NCI, CELLULAR & MOLEC BIOL LAB, BETHESDA, MD 20892 USA. UNIV PERUGIA, MONTELUCE POLICLIN, IST CLIN MED 1, I-06100 PERUGIA, ITALY. RP SEGATTO, O (reprint author), IST REGINA ELENA, CTR RIC SPERIMENTALE, IMMUNOL LAB, VIA MESSI ORO 156, I-00158 ROME, ITALY. RI Di Fiore, Pier Paolo/K-2130-2012; Pawson, Tony/E-4578-2013 OI Di Fiore, Pier Paolo/0000-0002-2252-0950; NR 45 TC 128 Z9 128 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD AUG PY 1993 VL 8 IS 8 BP 2105 EP 2112 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA LP171 UT WOS:A1993LP17100010 PM 8101647 ER PT J AU SKERKA, C ZIPFEL, PF SIEBENLIST, U AF SKERKA, C ZIPFEL, PF SIEBENLIST, U TI 2 REGULATORY DOMAINS ARE REQUIRED FOR DOWN-REGULATION OF C-MYC TRANSCRIPTION IN DIFFERENTIATING U937 CELLS SO ONCOGENE LA English DT Article ID BURKITT-LYMPHOMA; TRANS-ACTIVATION; DNA-REPLICATION; PROTEIN-BINDING; HL60 CELLS; EXPRESSION; GENE; ONCOGENE; PROMOTER; INITIATION AB In many differentiating cells, a reduction of c-myc proto-oncogene expression is a prerequisite for terminal differentiation. The downmodulation of c-myc in differentiating cells is due to at least two different mechanisms: (i) an elongation block to c-myc transcription activated during an early phase of differentiation and (ii) an inhibition of transcription initiation activated during a later phase. In order to determine cis-acting target structures of the c-myc gene required for the late-phase downregulation of transcriptional initiation, we permanently transfected U937 cells with constructs containing the bacterial chloramphenicol acetyl transferase (CAT) gene driven by a 2.8 kb c-myc promoter region or deletions thereof. We determined two distinct domains in the c-myc promoter region both of which are essential for efficient terminal downregulation: a proximal domain and a distal domain which are located between base pairs - 606 to - 101, and between - 2392 to - 1396, respectively, relative to P1. The identification of two distinct regulatory elements suggests the requirement and cooperation of two regulatory factors as an essential event for mediating differentiation-induced downregulation of c-myc in monocytic cells. The implications of these results for deregulation of the translocated c-myc allele in Burkitt's lymphoma are discussed. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RP SKERKA, C (reprint author), BERNHARD NOCHT INST TROP MED,BERNARD NOCHT STR 74,W-2000 HAMBURG 36,GERMANY. NR 37 TC 10 Z9 10 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG PY 1993 VL 8 IS 8 BP 2135 EP 2143 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA LP171 UT WOS:A1993LP17100014 PM 8336940 ER PT J AU ZAKUT, R PERLIS, R ELIYAHU, S YARDEN, Y GIVOL, D LYMAN, SD HALABAN, R AF ZAKUT, R PERLIS, R ELIYAHU, S YARDEN, Y GIVOL, D LYMAN, SD HALABAN, R TI KIT-LIGAND (MAST-CELL GROWTH-FACTOR) INHIBITS THE GROWTH OF KIT-EXPRESSING MELANOMA-CELLS SO ONCOGENE LA English DT Article ID FACTOR RECEPTOR PROTOONCOGENE; TYROSINE KINASE RECEPTOR; ACTIVATED PROTEIN-KINASE; CYTOMETRIC DNA ANALYSIS; W-MUTANT MICE; C-KIT; SI-LOCUS; SIGNAL TRANSDUCTION; FUNCTION MUTATIONS; HUMAN MELANOCYTES AB Previous studies in vivo and in vitro show that KIT kinase promotes normal melanocyte development and growth. However, the role of the KIT proto-oncogene in neoplastic melanocytes is not certain. We therefore examined KIT expression and function in human melanomas. Our results show that KIT mRNA was expressed in 12 of 28 melanoma cell lines (approximately 40%), mainly in those originating from pigmented tumors. Surprisingly, activation of KIT with mast cell growth factor (MGF) in melanoma cells produced biological responses opposite to those elicited in normal melanocytes. MGF inhibited rather than stimulated the growth of metastatic melanoma cell lines. The opposite effects may be due to aberrant signal transduction by KIT in melanoma cells in response to MGF. The in vitro inhibition of melanoma cells by MGF suggests that growth in vivo of this tumor is not promoted by KIT kinase activation, but rather that transformed melanocytes might regress when MGF is expressed in their immediate environment. C1 IMMUNEX RES & DEV CORP,SEATTLE,WA 98103. YALE UNIV,SCH MED,DEPT DERMATOL,NEW HAVEN,CT 06510. WEIZMANN INST SCI,DEPT CHEM IMMUNOL,IL-76100 REHOVOT,ISRAEL. RP ZAKUT, R (reprint author), NCI,SURG BRANCH,BETHESDA,MD 20892, USA. RI YARDEN, YOSEF/K-1467-2012 FU NCI NIH HHS [5-R29-CA44542]; NIAMS NIH HHS [1RO1-AR39848] NR 58 TC 89 Z9 89 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG PY 1993 VL 8 IS 8 BP 2221 EP 2229 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA LP171 UT WOS:A1993LP17100023 PM 7687762 ER PT J AU BUSAM, KJ GEISER, AG ROBERTS, AB SPORN, MB AF BUSAM, KJ GEISER, AG ROBERTS, AB SPORN, MB TI SYNERGISTIC INCREASE OF PHORBOL ESTER-INDUCED C-FOS MESSENGER-RNA EXPRESSION BY RETINOIC ACID THROUGH STABILIZATION OF THE C-FOS MESSAGE SO ONCOGENE LA English DT Article ID EMBRYONAL CARCINOMA-CELLS; ACUTE PROMYELOCYTIC LEUKEMIA; GENE-EXPRESSION; GROWTH-FACTORS; POSTTRANSCRIPTIONAL REGULATION; COLLAGENASE PRODUCTION; HOMEOBOX GENES; TRANSCRIPTION; INHIBITION; AP-1 AB Retinoic acid (RA) has been shown to be able to antagonize or synergize with phorbol 12-myristate 13-acetate (PMA). In contrast to its antagonistic effects on PMA-dependent gene expression, no molecular target or mechanism of synergism has been characterized yet. We now report, that RA synergistically enhances the induction of c-fos, but not c-jun mRNA by PMA in cells whose growth was stimulated by RA alone. The responding cells were hybrids of tumor cell lines whose growth and PMA-dependent c-fos mRNA expression remained unaffected by RA. The increase in PMA-dependent c-fos expression required pretreatment of cells with RA for at least 2 - 4 h and was achieved at doses as low as 10(-10) M. Nuclear run-on experiments and transient transfection assays using a chimeric reporter gene construct with sequences from the c-fos promoter indicated that RA did not affect PMA-dependent c-fos transcription. Instead, RA stabilized the c-fos message after induction by PMA as assessed by measuring the half-life of c-fos mRNA in actinomycin D-treated cells. This post-transcriptional regulation provides a mechanism whereby RA can synergistically enhance gene expression by PMA. RP BUSAM, KJ (reprint author), NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892, USA. NR 38 TC 13 Z9 13 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG PY 1993 VL 8 IS 8 BP 2267 EP 2273 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA LP171 UT WOS:A1993LP17100029 PM 8336949 ER PT J AU ALI, IU SAXENA, A MEISSNER, S BARRICK, J LIDEREAU, R AF ALI, IU SAXENA, A MEISSNER, S BARRICK, J LIDEREAU, R TI CLOSE PROXIMITY OF C-ERBA2 AND C-ERBA-BETA GENES ON THE SHORT ARM OF CHROMOSOME-3 SO ONCOGENE LA English DT Note ID THYROID-HORMONE RECEPTOR; RENAL-CELL CARCINOMA; HUMAN LUNG-CANCER; DELETION; LOCALIZATION; REGION; HETEROZYGOSITY; SEQUENCE; HOMOLOGS; PROTEIN AB The common loss region on the short arm of chromosome 3 (3p) in human breast tumors harbors two members of the c-erbA receptor gene family, c-erbA2 and c-erbA-beta, both of which recognize a BamHI polymorphism in human genomic DNA. Analysis of lymphocyte DNAs from 50 normal individuals and lymphocyte and tumor DNAs from 116 breast cancer patients revealed identical genotypes (a/a, b/b or a/b) for both probes. Furthermore, deletion of the same allele (a/- or -/b) of c-erbA2 and c-erbA-beta was detected in 25% of the 66 breast tumors from patients with constitutionally heterozygous genotypes for both genes. No sequence homology was detected between the c-erbA2 and c-erbA-beta genes, suggesting a physical linkage between these two genes. Digestion of the genomic DNA with combinations of restriction enzymes and hybridization with c-erbA2, which is a genomic fragment, and c-erbA-beta, which is a cDNA clone, provide evidence that c-erbA2 and a region of the c-erbA-beta gene are physically contiguous on the short arm of chromosome 3 and are separated by no more than 1.8 kb of DNA sequences. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. CTR RENE HUGUENIN,F-92211 ST CLOUD,FRANCE. RP ALI, IU (reprint author), NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892, USA. NR 25 TC 3 Z9 3 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG PY 1993 VL 8 IS 8 BP 2299 EP 2301 PG 3 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA LP171 UT WOS:A1993LP17100033 PM 8393165 ER PT J AU GUPTA, K COPELAND, NG GILBERT, DJ JENKINS, NA GRAY, DA AF GUPTA, K COPELAND, NG GILBERT, DJ JENKINS, NA GRAY, DA TI UNP, A MOUSE GENE-RELATED TO THE TRE ONCOGENE SO ONCOGENE LA English DT Note ID LINKAGE MAP; CLONING; SEQUENCES; REGION; CDNA; ADENOVIRUS-E1A; TRANSLATION; CARCINOMA; DELETION; PROTEIN AB We have cloned cDNAs from a novel gene designated Unp. Unp cDNAs contain a large open reading frame that would encode a protein of 89 kDa. The predicted protein contains a putative nuclear localization signal, as well as consensus sequences for binding to the retinoblastoma gene product. The latter elements are contained within a region having strong similarity to the human tre oncogene. We have localized the Unp gene to mouse chromosome 9 in a region of homology with human chromosome 3p. This region has been implicated in a number of human malignancies. C1 UNIV OTTAWA,DEPT BIOCHEM,451 SMYTH RD,OTTAWA K1H 8M5,ONTARIO,CANADA. NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,FREDERICK,MD 21702. UNIV OTTAWA,DEPT MED,OTTAWA K1H 8M5,ONTARIO,CANADA. FU NCI NIH HHS [N01-CO-74101] NR 24 TC 57 Z9 60 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG PY 1993 VL 8 IS 8 BP 2307 EP 2310 PG 4 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA LP171 UT WOS:A1993LP17100035 PM 8336951 ER PT J AU NOZAKI, T DVORAK, JA AF NOZAKI, T DVORAK, JA TI MOLECULAR-BIOLOGY STUDIES OF TUBERCIDIN RESISTANCE IN TRYPANOSOMA-CRUZI SO PARASITOLOGY RESEARCH LA English DT Article ID PYRIMIDINE METABOLISM; ALLOPURINOL; CHROMOSOMES; FALCIPARUM; STRAINS; PURINE; INVIVO AB Trypanosomatids are incapable of de novo purine synthesis; purines are obtained through the scavenging of exogenous nucleosides. To advance our understanding of purine utilization, we mutagenized a Trypanosoma cruzi stock and selected for resistance to high levels of tubercidin (7-deazaadanosine, TUB), a purine analog. The TUB-resistant stocks were > 100 times more resistant to TUB than was the parental stock. TUB and uridine transport in the TUB-resistant stocks decreased by 50%-90%, whereas thymidine and adenosine transport were unaffected. These data imply that TUB-resistant stocks have defects in the pathways involved in the transport of TUB and uridine but not in the thymidine and adenosine transport pathways. Karyotype analyses using specific probes showed that the deletion of a 950-kb chromosome-size DNA occurred in both of the TUB-resistant stocks. These data suggest that genes involved in nucleoside transport are located in this DNA region. This study will facilitate the identification and characterization of the specific genes involved in nucleoside transport and aid in the elucidation and development of new chemotherapeutics for Chagas' disease. C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. NR 21 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0044-3255 J9 PARASITOL RES JI Parasitol. Res. PD AUG PY 1993 VL 79 IS 6 BP 451 EP 455 DI 10.1007/BF00931581 PG 5 WC Parasitology SC Parasitology GA LT515 UT WOS:A1993LT51500003 PM 8415556 ER PT J AU DIGGS, CL BALLOU, WR MILLER, LH AF DIGGS, CL BALLOU, WR MILLER, LH TI THE MAJOR MEROZOITE SURFACE PROTEIN AS A MALARIA VACCINE TARGET SO PARASITOLOGY TODAY LA English DT Article ID MONOCLONAL-ANTIBODY RECOGNIZES; PLASMODIUM-FALCIPARUM; AOTUS MONKEYS; ANTIGEN GENE; PARASITE; RECOMBINANT; IMMUNIZATION; PRECURSOR; INVASION; EPITOPE AB Experts gathered for two days in the summer of 1992 at the National Institutes of Health and the Walter Reed Army Institute of Research to discuss the potential of a major merozoite surface protein (MSP-1) in malaria vaccine development. The participants came in an exemplary spirit of co-operation, sharing ideas and unpublished data toward the common goal of a malaria vaccine. Their conclusions are presented here by Carter Diggs, Ripley Ballou and Lou Miller. C1 WALTER REED ARMY MED CTR,WALTER REED ARMY INST RES,DEPT IMMUNOL,WASHINGTON,DC 20307. NIAID,MALARIA RES LAB,BETHESDA,MD 20892. RP DIGGS, CL (reprint author), ATLANTIC RESOURCES CORP,1601 N KENT ST,SUITE 1101,ARLINGTON,VA 22209, USA. NR 32 TC 49 Z9 51 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0169-4758 J9 PARASITOL TODAY JI Parasitol. Today PD AUG PY 1993 VL 9 IS 8 BP 300 EP 302 DI 10.1016/0169-4758(93)90130-8 PG 3 WC Parasitology SC Parasitology GA LN898 UT WOS:A1993LN89800014 PM 15463788 ER PT J AU ZULLO, S KENNEDY, JL GELERNTER, J POLYMEROPOULOS, MH TALLINI, G PAKSTIS, AJ SHAPIRO, MB MERRIL, CR KIDD, KK AF ZULLO, S KENNEDY, JL GELERNTER, J POLYMEROPOULOS, MH TALLINI, G PAKSTIS, AJ SHAPIRO, MB MERRIL, CR KIDD, KK TI ELIMINATING MITOCHONDRIAL-DNA COMPETITION FOR NUCLEAR-DNA PRIMERS SO PCR-METHODS AND APPLICATIONS LA English DT Article ID ARBITRARY PRIMERS; HUMAN GENOME; PCR; SEQUENCE; CDNA; GENE; RAT; RECEPTOR; CLONING; MARKERS AB Mitochondrial DNA (mtDNA) sequences were synthesized with nuclear DNA (nucDNA) sequence-tagged site (STS) primers by mismatch priming in three independent studies of the human nuclear genome. Mismatch primer binding sites on the mtDNA were identified with from 6- to 10-bp identity at the 3' ends of the primers. In two of three cases, single-stranded mtDNA copies were gel-isolated with intended nucDNA PCR products. During routine screening of the STSs, the radiolabeled gel-isolated products hybridized to polymorphic mtDNA restriction fragments. Intense signals after overnight exposure of radiolabeled PCR probes on Southern blots suggest contaminating mtDNA PCR products. The theoretical annealing temperatures of the mismatches were well below the annealing temperatures of the PCR primers, demonstrating annealing reactions driven by the molar surplus of the primers, that is, mass action. The probability that two primers (either one of a pair or both), designed to amplify nucDNA, will bind to and amplify mtDNA may be as high as 1 in 64, assuming that an identical match with only the 3' hexanucleotide is sufficient for amplification. To circumvent this problem we have developed OLIGFIND, a program that has identified the 104 of 4096 possible hexamers that are not present in human mtDNA. Our results suggest that time could be saved by designing STS primers with one of these 104 hexamers at the 3' end. OLIGFIND can also evaluate primer 3' ends for potential PCR products from mtDNA. C1 YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06510. YALE UNIV,SCH MED,DEPT PSYCHIAT,NEW HAVEN,CT 06510. YALE UNIV,SCH MED,DEPT PATHOL,NEW HAVEN,CT 06510. W HAVEN DEPT VET AFFAIRS MED CTR,W HAVEN,CT 06524. UNIV TORONTO,CLARKE INST PSYCHIAT,TORONTO M5T 1R8,ONTARIO,CANADA. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP ZULLO, S (reprint author), NIMH,MENTAL HLTH NEUROSCI CTR ST ELIZABETHS,BIOCHEM GENET LAB,WASHINGTON,DC 20032, USA. OI Tallini, Giovanni/0000-0003-0113-6682 FU NIMH NIH HHS [MH00931] NR 30 TC 7 Z9 7 U1 0 U2 2 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 AUG PY 1993 VL 3 IS 1 BP 39 EP 45 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA LX659 UT WOS:A1993LX65900007 PM 7693114 ER PT J AU SALLIE, R AF SALLIE, R TI CHARACTERIZATION OF THE EXTREME 5' ENDS OF RNA MOLECULES BY RNA LIGATION-PCR SO PCR-METHODS AND APPLICATIONS LA English DT Article ID HEPATITIS-C; VIRUS RP SALLIE, R (reprint author), NIDDK,LIVER DIS SECT,BETHESDA,MD 20892, USA. NR 10 TC 7 Z9 8 U1 0 U2 0 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 AUG PY 1993 VL 3 IS 1 BP 54 EP 56 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA LX659 UT WOS:A1993LX65900009 PM 7693115 ER PT J AU SCHNAPER, HW AF SCHNAPER, HW TI THE ENDOTHELIUM AS AN IMMUNE ORGAN - STUDIES OF ENDOTHELIAL-LEUKOCYTE INTERACTIONS SO PEDIATRIC NEPHROLOGY LA English DT Review DE LEUKOCYTE-ENDOTHELIAL INTERACTIONS RP SCHNAPER, HW (reprint author), NIDR,DEV BIOL LAB,BLDG 30,ROOM 407,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0931-041X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD AUG PY 1993 VL 7 IS 4 BP 496 EP 500 PG 5 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA LM629 UT WOS:A1993LM62900035 PM 8398666 ER PT J AU GAHL, WA BERNARDINI, IM DALAKAS, MC MARKELLO, TC KRASNEWICH, DM CHARNAS, LR AF GAHL, WA BERNARDINI, IM DALAKAS, MC MARKELLO, TC KRASNEWICH, DM CHARNAS, LR TI MUSCLE CARNITINE REPLETION BY LONG-TERM CARNITINE SUPPLEMENTATION IN NEPHROPATHIC CYSTINOSIS SO PEDIATRIC RESEARCH LA English DT Article ID RENAL FANCONI SYNDROME; FATTY-ACID OXIDATION; DEFICIENCY SYNDROMES; CULTURED MUSCLE; TRANSPORT; CHILDREN; CYSTEAMINE; THERAPY; STORAGE; PLASMA AB The renal tubular Fanconi syndrome of children with nephropathic cystinosis causes plasma and musle carnitine depletion. L-Carnitine replacement therapy for up to 18 mo has previously been shown to normalize plasma but not muscle carnitine levels. We treated six cystinosis patients, aged 1 to 4 y, with a mean dosage of 92 mg L-carnitine/kg/d given every 6 h for an average of 62 mo. Despite fractional excretions of free carnitine ranging from 55 to 108%, plasma-free and total carnitine concentrations were maintained at or above normal levels. At the end of the carnitine replacement period, the six children had muscle-free carnitine values ranging from 16.0 to 28.0 nmol/mg noncollagen protein compared with values of 3.0 to 11.4 for cystinosis children not supplemented with carnitine [normal, 22.7 +/- 5.0 (SD) nmol/mg protein]. Total muscle carnitine values were also normalized by L-carnitine replacement. The monthly increase in total body creatinine production, a measure of muscle mass, was higher (p = 0.036) in children with normal plasma free carnitine concentrations (3.4 +/- 0.9 mg/d) than in children with low plasma free carnitine (2.3 +/- 0.7 mg/d). No serious side effects, such as severe diarrhea, were observed. We conclude that oral L-carnitine replacement can normalize muscle carnitine content in children with cystinosis. C1 NICHHD,HUMAN GENET BRANCH,NEUROGENET UNIT,BETHESDA,MD 20892. NINCDS,MED NEUROL BRANCH,NEUROMUSCULAR DIS SECT,BETHESDA,MD 20892. RP GAHL, WA (reprint author), NICHHD,HUMAN BIOCHEM GENET SECT,BLDG 10,ROOM 9S-242,BETHESDA,MD 20892, USA. NR 40 TC 14 Z9 14 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD AUG PY 1993 VL 34 IS 2 BP 115 EP 119 DI 10.1203/00006450-199308000-00001 PG 5 WC Pediatrics SC Pediatrics GA LP075 UT WOS:A1993LP07500001 PM 8233709 ER PT J AU HORBAR, JD WRIGHT, EC ONSTAD, L PHILIPS, JB CASSADY, G FANAROFF, AA HACK, M EDWARDS, W LITTLE, GA FOLEY, KA BAUER, CR BANDSTRA, ES YAFFE, SJ WRIGHT, LL MALLOY, MH KORONES, SB COOKE, R TYSON, JE UAUY, RD LUCEY, JF SHANKARAN, S OSTREA, E AF HORBAR, JD WRIGHT, EC ONSTAD, L PHILIPS, JB CASSADY, G FANAROFF, AA HACK, M EDWARDS, W LITTLE, GA FOLEY, KA BAUER, CR BANDSTRA, ES YAFFE, SJ WRIGHT, LL MALLOY, MH KORONES, SB COOKE, R TYSON, JE UAUY, RD LUCEY, JF SHANKARAN, S OSTREA, E TI DECREASING MORTALITY ASSOCIATED WITH THE INTRODUCTION OF SURFACTANT THERAPY - AN OBSERVATIONAL STUDY OF NEONATES WEIGHING 601 TO 1300 GRAMS AT BIRTH SO PEDIATRICS LA English DT Article DE SURFACTANT; NEONATE; MORTALITY; OUTCOMES; BEFORE-AFTER TRIAL ID RESPIRATORY-DISTRESS SYNDROME; 30 WEEKS GESTATION; CONTROLLED TRIAL; BRONCHOPULMONARY DYSPLASIA; SYNTHETIC SURFACTANT; REPLACEMENT THERAPY; INFANTS; LESS; PROPHYLAXIS; SURVIVAL AB Objective. To determine whether the introduction of surfactant therapy was associated with decreased mortality for high-risk preterm neonates weighing 601 to 1300 g at birth. Design. Before-after observational study. Setting. Eight tertiary care neonatal intensive care units participating in the National Institute of Child Health and Human Development Neonatal Research Network. Patients. The outcomes for neonates with birth weight 601 to 1300 g admitted in the 2 years before surfactants became available (n = 2780) were compared with those of neonates admitted in the year beginning 2 months after surfactants became available (n = 1413). Main outcome measures. The primary outcome measure was in-hospital mortality; secondary outcome measures included durations of assisted ventilation, length of hospitalization, and neonatal morbidity. Results. Forty percent of neonates in the postsurfactant group received surfactant (range 28% to 69% at the centers). Mortality decreased from 27.8% before to 19.9% after surfactant therapy was introduced (Mantel-Haenszel chi2 = 31.4, P = .001). The adjusted odds ratio for mortality after surfactants became available was 0.73 (95% confidence interval 0.55 to 0.95). The duration of assisted ventilation and length of hospitalization increased after surfactants were introduced (P = .0001 for both outcomes). Conclusion. Mortality for neonates weighing 601 to 1300 g decreased after surfactant therapy was introduced, suggesting that the efficacy of surfactants demonstrated in randomized controlled trials will translate into effectiveness in routine clinical care. C1 UNIV ALABAMA,BIRMINGHAM,AL 35294. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. DARTMOUTH COLL,HITCHCOCK MED CTR,HANOVER,NH 03756. GEORGE WASHINGTON UNIV,CTR BIOSTAT COORDINATING,WASHINGTON,DC 20052. UNIV MIAMI,CORAL GABLES,FL 33124. NICHHD,BETHESDA,MD 20892. UNIV TENNESSEE CTR HLTH SCI,MEMPHIS,TN 38163. UNIV TEXAS,SW MED CTR,DALLAS,TX 75230. WAYNE STATE UNIV,DETROIT,MI 48202. RP HORBAR, JD (reprint author), UNIV VERMONT,COLL MED,DEPT PEDIAT,GIVEN BLDG,BURLINGTON,VT 05405, USA. NR 26 TC 140 Z9 142 U1 1 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD AUG PY 1993 VL 92 IS 2 BP 191 EP 196 PG 6 WC Pediatrics SC Pediatrics GA LQ811 UT WOS:A1993LQ81100001 PM 7710456 ER PT J AU KNOX, SS AF KNOX, SS TI PERCEPTION OF SOCIAL SUPPORT AND BLOOD-PRESSURE IN YOUNG MEN SO PERCEPTUAL AND MOTOR SKILLS LA English DT Article ID CARDIOVASCULAR REACTIVITY; HYPERTENSION; MORTALITY; DISEASE; MODEL AB This study investigated the association between perceived social support, blood pressure, and heart rate during rest and stress. 29 men were selected from 184 students on the basis of having high and low perceived social support. During rest and two of the laboratory stressors, the low-support group had higher diastolic pressure than the high-support group. Systolic blood pressure and heart rate did not differ between the two groups during either rest or stress. The low-support group was slightly older (24.8 yr.) than the high-support group (22.4 yr.), but the groups did not differ with respect to parental history of hypertension, body mass index, smoking, anxiety, anger inhibition, or environmental stress. RP KNOX, SS (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 9 TC 24 Z9 25 U1 0 U2 1 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 AUG PY 1993 VL 77 IS 1 BP 132 EP 134 PG 3 WC Psychology, Experimental SC Psychology GA LR956 UT WOS:A1993LR95600025 PM 8367230 ER PT J AU CUSTER, M MEIER, F SCHLATTER, E GREGER, R GARCIAPEREZ, A BIBER, J MURER, H AF CUSTER, M MEIER, F SCHLATTER, E GREGER, R GARCIAPEREZ, A BIBER, J MURER, H TI LOCALIZATION OF NAPI-1, A NA-PI COTRANSPORTER, IN RABBIT KIDNEY PROXIMAL TUBULES .1. MESSENGER-RNA LOCALIZATION BY REVERSE TRANSCRIPTION-POLYMERASE CHAIN-REACTION SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE PROXIMAL TUBULE; NEPHRON MICRODISSECTION; RT (REVERSE TRANSCRIPTASE)/PCR (POLYMERASE CHAIN REACTION); PHOSPHATE REABSORPTION; BRUSH-BORDER MEMBRANE; EXPRESSION CLONING ID PHOSPHATE-TRANSPORT; CELLULAR MECHANISMS; INORGANIC-PHOSPHATE; MOLECULAR-CLONING; MEMBRANE-VESICLES; NA+/H+ EXCHANGER; AMINO-ACIDS; RAT-KIDNEY; CDNA; EXPRESSION AB We have recently isolated from a rabbit cortex cDNA library a cDNA clone (NaPi-1), which, after in vitro transcription (cRNA) and injection into Xenopus laevis oocytes, expresses Na-dependent P(i) uptake [Werner A, et al. (1991) Proc Natl Acad Sci USA 88:9608-9612]. The aim of the present work was to study the nephron location of the NaPi-1-related mRNA(s) by combining nephron microdissection procedures, reverse transcription (RT) and amplification of the resultant cDNA by the polymerase chain reaction (PCR). RT-PCR using NaPi-1-specific primers (different combinations) and either total kidney cortex RNA or microdissected proximal tubule segments resulted in two PCR products, both of approximately the expected length (but differing by about 30 base pairs). Restriction-enzyme analysis and nucleotide sequencing confirmed that both PCR products are related to NaPi-1 and that the ''longer'' PCR product has an insert of 26 base pairs containing an AluI restriction site. Nephron microdissection documents expression of NaPi-1-related mRNA(s) in superficial and deep proximal tubules (S1, S2 and S3 segments) and their absence in glomeruli, thin descending limb and thick ascending limbs of Henle's loop, distal convoluted tubules and cortical and inner medullary collecting ducts. These experiments suggest a ''microheterogeneity'' of NaPi-1-related mRNA(s) (which is not detected in Northern blot analysis) and proximal tubular expression of NaPi-1. C1 UNIV ZURICH,INST PHYSIOL,WINTERTHURERSTR 190,CH-8057 ZURICH,SWITZERLAND. UNIV FREIBURG,INST PHYSIOL,W-7800 FREIBURG,GERMANY. NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. NR 32 TC 58 Z9 58 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD AUG PY 1993 VL 424 IS 3-4 BP 203 EP 209 DI 10.1007/BF00384343 PG 7 WC Physiology SC Physiology GA LP931 UT WOS:A1993LP93100002 PM 8414907 ER PT J AU HULIHANGIBLIN, BA PIVORUN, EB GOLDMAN, D AF HULIHANGIBLIN, BA PIVORUN, EB GOLDMAN, D TI DIURNAL RHYTHMS OF 5-HT(1A) AND 5-HT(2) RECEPTOR-BINDING IN EUTHERMIC AND TORPOR PRONE DEERMICE, PEROMYSCUS-MANICULATUS SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE DEERMOUSE; TORPOR; SEROTONIN; DIURNAL RHYTHMS; 5-HT(1A) RECEPTOR; 5-HT(2) RECEPTOR ID CIRCADIAN-RHYTHM; FUNCTIONAL-ROLE; RAT; SEROTONIN; 8-OH-DPAT; AGONIST; 5-HT1A; SITES; DOPAMINE; LIGAND AB Deermice display both spontaneous and induced daily torpor bouts, attaining minimum body temperatures of 15-20-degrees-C. There is evidence that brain serotonin may be involved in the initiation and/or maintenance of torpor. Inhibition of serotonin [5-hydroxytryptamine (5-HT)] synthesis markedly reduces the duration and depth of torpor. Because a certain percentage of deermice will not enter torpor under any circumstances, we were able to compare 5-HT receptor subtypes in deermice that readily enter into torpor (TP) and in non-torpor prone (NTP) animals. Deermice were trapped in the wild and subjected to food rationing and low ambient temperature and then sacrificed either in a normothermic or torpid state at 11:00 p.m. or 11:00 a.m. Whole brain was assayed for 5-HT1A and 5-HT2 receptor differences using [H-3]8-OH-DPAT and [H-3]ketanserin, respectively. The B(max) values for 5-HT1A receptors were significantly greater in both TP and NTP animals sacrificed at 11:00 p.m. compared to animals sacrificed at 11:00 a.m. In contrast, the density of 5-HT2 receptors was significantly greater in animals sacrificed at 11:00 a.m. compared to animals sacrificed at 11:00 p.m. This is consistent with the opposing functions of these receptors in the regulation of temperature and sleep. The affinity (K(d)) of each receptor was unchanged. A comparison of TP and NTP animals sacrificed at the same time of day revealed no significant differences in either B(max) or in K(d) values, indicating that differences in 5-HT1A and 5-HT2 receptors may not explain the heterogeneity of deermice in their ability to enter torpor. However, the diurnal fluctuation in 5-HT receptors described here may be involved in the serotonergic regulation of hormone rhythmicity and the onset of torpor in deermice. C1 CLEMSON UNIV,DEPT BIOL SCI,CLEMSON,SC 29634. RP HULIHANGIBLIN, BA (reprint author), NIAAA,CTR CLIN,NEUROGENET LAB,ROOM 3C-216,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 21 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD AUG PY 1993 VL 45 IS 4 BP 785 EP 789 DI 10.1016/0091-3057(93)90121-9 PG 5 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA LP737 UT WOS:A1993LP73700004 PM 8415817 ER PT J AU GANDJBAKHCHE, AH WEISS, GH BONNER, RF NOSSAL, R AF GANDJBAKHCHE, AH WEISS, GH BONNER, RF NOSSAL, R TI PHOTON PATH-LENGTH DISTRIBUTIONS FOR TRANSMISSION THROUGH OPTICALLY TURBID SLABS SO PHYSICAL REVIEW E LA English DT Article ID PHOTODYNAMIC THERAPY; TISSUE; TIME; MEDIA AB A discrete stochastic model is used to derive analytic expressions for various quantities relating to photon transport through an optically turbid slab. Several theoretical predictions, including those of the distributions of total path length, diffuse surface reemissions, and time-resolved point intensities, are examined by comparison with Monte Carlo simulations of a continuous-random-walk model of photon migration through a semi-infinite medium of finite thickness. RP GANDJBAKHCHE, AH (reprint author), NIH,BETHESDA,MD 20892, USA. RI Bonner, Robert/C-6783-2015 NR 29 TC 47 Z9 47 U1 0 U2 2 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 AUG PY 1993 VL 48 IS 2 BP 810 EP 818 DI 10.1103/PhysRevE.48.810 PG 9 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA LV383 UT WOS:A1993LV38300029 ER PT J AU MASOLIVER, J PORRA, JM WEISS, GH AF MASOLIVER, J PORRA, JM WEISS, GH TI SOLUTION TO THE TELEGRAPHERS EQUATION IN THE PRESENCE OF REFLECTING AND PARTLY REFLECTING BOUNDARIES SO PHYSICAL REVIEW E LA English DT Article ID HEAT WAVES; DIFFUSION; TIME AB We show that the reflecting boundary condition for a one-dimensional telegrapher's equation is the same as that for the diffusion equation, in contrast to what is found for the absorbing boundary condition. The radiation boundary condition is found to have a quite complicated form. We, also obtain exact solutions of the telegrapher's equation in the presence of these boundaries. C1 NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP MASOLIVER, J (reprint author), UNIV BARCELONA,DEPT FIS FONAMENTAL,DIAGONAL 647,E-08028 BARCELONA,SPAIN. RI Masoliver, Jaume/F-7198-2016 OI Masoliver, Jaume/0000-0002-5810-879X NR 17 TC 38 Z9 38 U1 0 U2 4 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 AUG PY 1993 VL 48 IS 2 BP 939 EP 944 DI 10.1103/PhysRevE.48.939 PG 6 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA LV383 UT WOS:A1993LV38300043 ER PT J AU URABE, K AROCA, P HEARING, VJ AF URABE, K AROCA, P HEARING, VJ TI FROM GENE TO PROTEIN - DETERMINATION OF MELANIN SYNTHESIS SO PIGMENT CELL RESEARCH LA English DT Article DE MELANIN; MELANOGENESIS; MOLECULAR BIOLOGY; PIGMENT GENES ID IA OCULOCUTANEOUS ALBINISM; HUMAN TYROSINASE GENE; CELL-SPECIFIC EXPRESSION; SINGLE BASE INSERTION; COAT COLOR LOCUS; MOUSE TYROSINASE; MOLECULAR-BASIS; POINT MUTATION; HUMAN HOMOLOG; PRADER-WILLI AB Melanin production in mammals is regulated at a variety of levels (tissue, cellular, and subcellular), and many gene loci are involved in the determination of color patterns directed by the melanocyte. Many of the genes involved in these complex processes have now been cloned, and even the simplest mutation can lead to dramatic changes in the phenotype of the individual. Many, if not all, of the pigment related genes have pleiotropic effects on the development and differentiation of the organism, and perhaps because of this, the melanocyte is evolving as an important model for the study of gene regulation and action at the functional level. In view of the importance of pigmentation as a photoprotective barrier and as a cosmetic factor affecting appearance and social acceptance, the importance of these studies seems destined to increase significantly in the future. C1 NCI,CELL BIOL LAB,BLDG 37,ROOM 1B25,BETHESDA,MD 20892. NR 80 TC 39 Z9 39 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD AUG PY 1993 VL 6 IS 4 BP 186 EP 192 DI 10.1111/j.1600-0749.1993.tb00601.x PN 1 PG 7 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA MA167 UT WOS:A1993MA16700003 PM 8248015 ER PT J AU LANGFELDER, EJ JUENGST, ET AF LANGFELDER, EJ JUENGST, ET TI ETHICAL, LEGAL, AND SOCIAL IMPLICATIONS (ELSI) PROGRAM - NATIONAL-CENTER-FOR-HUMAN-GENOME-RESEARCH, NATIONAL-INSTITUTES-OF-HEALTH SO POLITICS AND THE LIFE SCIENCES LA English DT Editorial Material RP LANGFELDER, EJ (reprint author), NIH,NATL CTR HUMAN GENOME RES,ELSI BRANCH,BETHESDA,MD 20892, USA. OI Juengst, Eric/0000-0002-8374-5774 NR 0 TC 6 Z9 6 U1 0 U2 1 PU BEECH TREE PUBLISHING PI GUILDFORD PA 10 WATFORD CLOSE, GUILDFORD, SURREY, ENGLAND GU1 2EP SN 0730-9384 J9 POLIT LIFE SCI JI Polit. Life Sci. PD AUG PY 1993 VL 12 IS 2 BP 273 EP 275 PG 3 WC Biology; History & Philosophy Of Science; Social Issues SC Life Sciences & Biomedicine - Other Topics; History & Philosophy of Science; Social Issues GA LV379 UT WOS:A1993LV37900024 PM 11654724 ER PT J AU PRASAD, GL FULDNER, RA COOPER, HL AF PRASAD, GL FULDNER, RA COOPER, HL TI EXPRESSION OF TRANSDUCED TROPOMYOSIN-1 CDNA SUPPRESSES NEOPLASTIC GROWTH OF CELLS TRANSFORMED BY THE RAS ONCOGENE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MAMMARY EPITHELIAL-CELLS; HUMAN FIBROBLAST; CULTURED-CELLS; PROTEIN; GENE; ACTIN; TUMORIGENICITY; ORGANIZATION; RETROVIRUS; NONMUSCLE AB Synthesis of certain members of the tropomyosin family of microfilament-associated proteins is suppressed in fibroblasts neoplastically transformed by a number of retroviral oncogenes, by transforming growth factor a, and by chemical mutagens. To test whether tropomyosin suppression is a required event in neoplastic transformation, expression of one of two suppressed tropomyosins in NIH 3T3 mouse cells transformed by the ras oncogene was restored by retro-virally mediated cDNA transfer. Cells expressing the inserted cDNA showed partial restoration of microfilament bundle formation (which is typically deranged in transformed cells) together with increased cytoplasmic spreading. More importantly, they lost anchorage-independent growth capability, and the onset of tumor growth in athymic mice was delayed. When tumors arose they no longer expressed the inserted cDNA. These observations support the conclusion that tropomyosin suppression is a necessary event for the expression of components of the transformed phenotype, particularly with respect to anchorage-independent growth and tumorigenesis, which correlate closely with neoplastic potential. This potentially reversible requirement may link different initial events produced by a variety of oncogenic modalities to a common pathway leading to neoplastic growth. C1 NCI,CELL & MOLEC PHYSIOL SECT,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NR 44 TC 169 Z9 172 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 AUG 1 PY 1993 VL 90 IS 15 BP 7039 EP 7043 DI 10.1073/pnas.90.15.7039 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LQ335 UT WOS:A1993LQ33500031 PM 8346214 ER PT J AU MUEGGE, K VILA, M GUSELLA, GL MUSSO, T HERRLICH, P STEIN, B DURUM, SK AF MUEGGE, K VILA, M GUSELLA, GL MUSSO, T HERRLICH, P STEIN, B DURUM, SK TI INTERLEUKIN-1 INDUCTION OF THE C-JUN PROMOTER SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID COLLAGENASE GENE; PROTO-ONCOGENE; TRANSCRIPTION; CELLS; EXPRESSION; AP-1; ACTIVATION; ACID; FOS; STIMULATION AB Interleukin 1 (IL-1) induces pleiotropic effects in many cell types during inflammation and immunity. We have recently shown how the IL-1 signal is transmitted to the nucleus: In T cells and in pituitary cells, IL-1 induced genes via activation of the nuclear factor AP-1. We now demonstrate how IL-1 activates the AP-1 factor in liver cells, which are a major target for IL-1 during the acute phase response in vivo. IL-1 induced gene transcription of both AP-1 components, c-jun and c-fos. IL-1 also increased the stability of c-jun mRNA. We define two enhancer sites in the jun promoter that are required for induction by IL-1. Although the binding sites share some similarity with the AP-1 binding site, the nuclear factors binding the jun motifs are not composed of Jun or Fos proteins. Thus these data identify two binding proteins that serve as one of the first nuclear targets for IL-1 signal transduction. C1 NCI,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702. KERNFORSCHUNGSZENTRUM KARLSRUHE GMBH,INST GENET & TOXIKOL,W-7500 KARLSRUHE 1,GERMANY. RP MUEGGE, K (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702, USA. FU PHS HHS [N01-C0-74102] NR 37 TC 73 Z9 73 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 AUG 1 PY 1993 VL 90 IS 15 BP 7054 EP 7058 DI 10.1073/pnas.90.15.7054 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LQ335 UT WOS:A1993LQ33500034 PM 8346217 ER PT J AU DEALDANA, CRV DEVER, TE HINNEBUSCH, AG AF DEALDANA, CRV DEVER, TE HINNEBUSCH, AG TI MUTATIONS IN THE ALPHA-SUBUNIT OF EUKARYOTIC TRANSLATION INITIATION FACTOR-II (EIF-2-ALPHA) THAT OVERCOME THE INHIBITORY EFFECT OF EIF-2-ALPHA PHOSPHORYLATION ON TRANSLATION INITIATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PROTEIN KINASE GCN2; GCN4; GUANINE NUCLEOTIDE EXCHANGE FACTOR ID SACCHAROMYCES-CEREVISIAE; GCN4 EXPRESSION; KINASE GCN2; YEAST; PROTEIN; GENE; ACID; SUPPRESSION; CLONING; RNA AB Phosphorylation of eIF-2alpha in Saccharomyces cerevisiae by the protein kinase GCN2 leads to inhibition of general translation initiation and a specific increase in translation of GCN4 mRNA. We isolated mutations in the eIF-2alpha structural gene that do not affect the growth rate of wild-type yeast but which suppress the toxic effects of eIF-2alpha hyperphosphorylation catalyzed by mutationally activated forms of GCN2. These eIF-2alpha mutations also impair translational derepression of GCN4 in strains expressing wild-type GCN2 protein. All four mutations alter single amino acids within 40 residues of the phosphorylation site in eIF-2alpha; however, three alleles do not decrease the level of eIF-2alpha phosphorylation. We propose that these mutations alter the interaction between eIF-2 and its recycling factor eukaryotic translation initiation factor 2B (eIF-2B) in a way that diminishes the inhibitory effect of phosphorylated eIF-2 on the essential function of eIF-2B-in translation initiation. These mutations may identify a region m eIF-2alpha that participates directly in a physical interaction with the GCN3 subunit of eIF-2B. RP NICHHD, MOLEC GENET LAB, MOLEC GENET LOWER EUKARYOTES SECT, BETHESDA, MD 20892 USA. RI Vazquez de Aldana, Carlos/B-7772-2008 OI Vazquez de Aldana, Carlos/0000-0002-4513-3654 NR 22 TC 40 Z9 41 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 AUG 1 PY 1993 VL 90 IS 15 BP 7215 EP 7219 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LQ335 UT WOS:A1993LQ33500067 ER PT J AU PARRIS, CN KRAEMER, KH AF PARRIS, CN KRAEMER, KH TI ULTRAVIOLET-INDUCED MUTATIONS IN COCKAYNE-SYNDROME CELLS ARE PRIMARILY CAUSED BY CYCLOBUTANE DIMER PHOTOPRODUCTS WHILE REPAIR OF OTHER PHOTOPRODUCTS IS NORMAL SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DNA REPAIR; XERODERMA-PIGMENTOSUM; SKIN CANCER; SHUTTLE VECTOR; PHOTOREACTIVATION ID XERODERMA PIGMENTOSUM-CELLS; ESCHERICHIA-COLI; INCREASED SENSITIVITY; PYRIMIDINE DIMERS; DNA-SYNTHESIS; LIGHT; FIBROBLASTS; MUTAGENESIS; DAMAGE; LINES AB We compared the contribution to mutagenesis in Cockayne syndrome (CS) cells of the major class of UV photoproducts, the cyclobutane pyrimidine dimer, to that of other DNA photoproducts by using the mutagenesis shuttle vector pZ189. Lymphoblastoid cell lines from the DNA repair-deficient disorders CS and xeroderma pigmentosum (XP) and a normal line were transfected with UV-treated pZ189. Cyclobutane dimers were selectively removed before transfection by photoreactivation (PR), leaving nondimer photoproducts intact. After UV exposure and replication in CS and XP cells, plasmid survival was abnormally reduced and mutation frequency was abnormally elevated. After PR, plasmid survival increased and mutation frequency in CS cells decreased to normal levels but remained abnormal in XP cells. Sequence analysis of >200 mutant plasmids showed that with CS cells a major mutational hot spot was caused by unrepaired cyclobutane dimers. These data indicate that with both CS and XP cyclobutane dimers are major photoproducts generating reduced plasmid survival and increased mutation frequency. However, unlike XP, CS cells are proficient in repair of nondimer photoproducts. Since XP but not CS patients have a high frequency of UV-induced skin cancers, our data suggest that prevention of UV-induced skin cancers is associated with proficient repair of nondimer photoproducts. C1 NCI,MOLEC CARCINOGENESIS LAB,BLDG 37,ROOM 3E24,BETHESDA,MD 20892. FU Intramural NIH HHS [Z01 BC004517-31] NR 38 TC 55 Z9 55 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 AUG 1 PY 1993 VL 90 IS 15 BP 7260 EP 7264 DI 10.1073/pnas.90.15.7260 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LQ335 UT WOS:A1993LQ33500076 PM 8346243 ER PT J AU JANZ, S MULLER, J SHAUGHNESSY, J POTTER, M AF JANZ, S MULLER, J SHAUGHNESSY, J POTTER, M TI DETECTION OF RECOMBINATIONS BETWEEN C-MYC AND IMMUNOGLOBULIN SWITCH ALPHA IN MURINE PLASMA-CELL TUMORS AND PRENEOPLASTIC LESIONS BY POLYMERASE CHAIN-REACTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PROTOONCOGENE; CHROMOSOMAL TRANSLOCATION; GENE REARRANGEMENT; PLASMACYTOMAGENESIS; BALB/C MOUSE ID HUMAN B-CELLS; CHROMOSOME-TRANSLOCATION; MOUSE PLASMACYTOMAS; RECIPROCAL EXCHANGE; MOLECULAR ANALYSIS; DNA-SEQUENCES; IGH LOCI; ONCOGENE; ISOTYPE; REARRANGEMENTS AB Virtually all murine plasmacytomas carry chromosomal translocations that activate c-myc. The predominant (almost-equal-to 90%) c-myc-activating chromosomal translocation in pristane (2,6,10,14-tetramethylpentadecane)-induced plasmacytomas in BALB/c mice is a reciprocal translocation t(12;15) in which an immunoglobulin heavy-chain switch sequence is joined to the 5' region of c-myc. The most common switch region involved is S(alpha). We developed a direct PCR method to screen for recombinations between c-myc and S(alpha). The critical step in establishing the method was the cloning and sequencing of the 5' flank of C(alpha), a region with a reduced number of switch repeats that is much more favorable for designing specific PCR primers than the highly repetitive S(alpha) region. In applying this PCR method, we detected translocation-specific junction fragments in transplanted (10/16, 63%) and primary (5/15, 33%) plasmacytomas. Moreover, the sensitivity of a nested version of that technique allowed us to discern rare t(12;15)s in BALB/c mice in the preneoplastic stage of plasmacytoma-genesis (8/20 mice, 40%) as early as 30 days after administration of pristane. We conclude that t(12;15) is the probable primary, if not initiating, oncogenic step in plasmacytomagenesis. RP JANZ, S (reprint author), NCI,DIV CANC BIOL DIAGNOSIS & CTR,GENET LAB,BETHESDA,MD 20814, USA. NR 32 TC 60 Z9 60 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 AUG 1 PY 1993 VL 90 IS 15 BP 7361 EP 7365 DI 10.1073/pnas.90.15.7361 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LQ335 UT WOS:A1993LQ33500097 PM 8346257 ER PT J AU COHEN, JI SEIDEL, KE AF COHEN, JI SEIDEL, KE TI GENERATION OF VARICELLA-ZOSTER VIRUS (VZV) AND VIRAL MUTANTS FROM COSMID DNAS - VZV THYMIDYLATE SYNTHETASE IS NOT ESSENTIAL FOR REPLICATION IN-VITRO SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE RECOMBINATION; HERPESVIRUS; VACCINE ID PSEUDORABIES VIRUS; HERPES-SIMPLEX; CELL LINE; VACCINE; GENE; HERPESVIRUSES; LYMPHOCYTES; EXPRESSION; SYNTHASE; PROTEIN AB Four overlapping cosmid clones were constructed that contain the complete genome of the attenuated Oka strain of VZV. Transfection of human melanoma cells with the four cosmids resulted in production of infectious VZV. A double-stranded oligonucleotide, encoding a stop codon in all three open reading frames, was inserted into one of the cosmids at the 5' end of the viral thymidylate synthetase gene. Transfection of melanoma cells with the mutant cosmid, along with the other three cosmids, resulted in VZV that does not express the viral thymidylate synthetase protein. The mutant virus grew at a rate similar to that of the parental Oka strain virus. Production of recombinant VZV using cosmid DNAs will be useful for studying the function of viral genes in VZV replication and establishment of latency. Furthermore, manipulation of the Oka strain of VZV might allow one to produce a vaccine virus that does not establish latency in the central nervous system or a virus that encodes foreign antigens for use as a polyvalent live virus vaccine. RP COHEN, JI (reprint author), NIAID,CLIN INVEST LAB,BETHESDA,MD 20892, USA. NR 23 TC 123 Z9 126 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 AUG 1 PY 1993 VL 90 IS 15 BP 7376 EP 7380 DI 10.1073/pnas.90.15.7376 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LQ335 UT WOS:A1993LQ33500100 PM 8394020 ER PT J AU ZEEVAART, JAD GAGE, DA TALON, M AF ZEEVAART, JAD GAGE, DA TALON, M TI GIBBERELLIN-A(1) IS REQUIRED FOR STEM ELONGATION IN SPINACH SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GROWTH RETARDANT; GAS CHROMATOGRAPHY MASS SPECTROMETRY; PHOTOPERIOD; QUANTIFICATION ID PROHEXADIONE-CALCIUM BX-112; PLANT-GROWTH REGULATOR; EXOGENOUSLY APPLIED GIBBERELLINS; ENDOGENOUS GIBBERELLINS; SILENE-ARMERIA; SEEDLINGS; RETARDANT; RICE; PHOTOPERIOD; INHIBITION AB The effects of the growth retardants 2'-isopropyl-4'-(trimethylammonium chloride)-5'-methylphenyl piperidine-1-carboxylate (AMO-1618) and calcium 3,5-dioxo-4-propionylcylohexanecarboxylate (BX-112) on stem elongation were investigated in the rosette plant spinach (Spinacia oleracea L.) under long-day (LD) conditions. Stem growth induced by a LD treatment was prevented by both retardants. The inhibition caused by AMO-1618 was reversed by gibberellin A1 (GA1) and GA20, whereas the effects of BX-112 were reversed by GA1 only. Six GAs (GA53, GA44, GA19, GA20, GA1, and GA8) were quantified by gas chromatography-selected ion monitoring using internal standards. Plants treated with BX-112 had reduced levels of GA1 and GA8 and accumulated GA53, GA44, GA19, and GA20. The relative levels of four additional GAs (3-epi-GA1, GA29, GA60, and GA81) were compared by ion intensities only. Relative to GA81, the level of GA29 was decreased by BX-112, whereas the levels of GA60 and 3-epi-GA1 were increased. Transfer of spinach from short-day conditions to LD conditions caused an increase in all identified GAs of the early 13-hydroxylation pathway with GA20, GA1, and GA8 showing the largest increases. These findings support the position that, of the GAs belonging to the early 13-hydroxylation pathway, GA1 is the primary GA active per se for stem elongation in spinach. The increase in endogenous GA1 in plants in LD conditions is most likely the primary factor for stem elongation. C1 MICHIGAN STATE UNIV,NIH,DEPT BIOCHEM,MASS SPECT FACIL,E LANSING,MI 48824. RP ZEEVAART, JAD (reprint author), MICHIGAN STATE UNIV,DEPT ENERGY PLANT,RES LAB,E LANSING,MI 48824, USA. RI Talon, Manuel/C-8540-2014 OI Talon, Manuel/0000-0003-4291-9333 NR 23 TC 79 Z9 81 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 AUG 1 PY 1993 VL 90 IS 15 BP 7401 EP 7405 DI 10.1073/pnas.90.15.7401 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LQ335 UT WOS:A1993LQ33500105 PM 11607418 ER PT J AU KAWA, S KUMAR, A SMITH, JS BECERRA, SP BEARD, WA WILSON, SH THOMPSON, EB AF KAWA, S KUMAR, A SMITH, JS BECERRA, SP BEARD, WA WILSON, SH THOMPSON, EB TI EXPRESSION AND PURIFICATION OF THE HIV-1 REVERSE-TRANSCRIPTASE USING THE BACULOVIRUS EXPRESSION VECTOR SYSTEM SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID HIGH-LEVEL EXPRESSION; ESCHERICHIA-COLI; AIDS VIRUS; GLUCOCORTICOID RECEPTOR; INSECT CELLS; PROTEIN; BINDING; CLEAVAGE C1 UNIV TEXAS,MED BRANCH,DEPT HUMAN BIOL CHEM & GENET,BSB,ROOM 603,GALVESTON,TX 77550. UNIV TEXAS,MED BRANCH,SEALY CTR MOLEC SCI,GALVESTON,TX 77550. NCI,BIOCHEM LAB,BETHESDA,MD 20892. FU NIDDK NIH HHS [5R01 DK41058] NR 25 TC 4 Z9 5 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 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD AUG PY 1993 VL 4 IS 4 BP 298 EP 303 DI 10.1006/prep.1993.1038 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA LN341 UT WOS:A1993LN34100005 PM 7690627 ER PT J AU MOLDIN, SO SCHEFTNER, WA RICE, JP NELSON, E KNESEVICH, MA AKISKAL, H AF MOLDIN, SO SCHEFTNER, WA RICE, JP NELSON, E KNESEVICH, MA AKISKAL, H TI ASSOCIATION BETWEEN MAJOR DEPRESSIVE DISORDER AND PHYSICAL ILLNESS SO PSYCHOLOGICAL MEDICINE LA English DT Article ID MEDICAL ILLNESS; YOUNG-ADULTS; MIGRAINE; PREVALENCE; HEADACHE; SYMPTOMS; CANCER; RISK AB The association between major depressive disorder (MDD) and self-reported histories of specific physical illnesses was investigated in 320 controls and 1968 first-degree relatives and 254 spouses of probands in the NIMH Collaborative Depression study. The Schedule for Affective Disorders and Schizophrenia-Lifetime Version was used to assign Research Diagnostic Criteria (RDC) diagnoses and a structured self-report instrument was used to assess lifetime medical history. Lifetime MDD was diagnosed in 914 subjects, 402 of whom had been hospitalized or received somatic treatment ('treated' MDD). Strong associations were observed between MDD (either treated or untreated) and both frequent/severe headaches and migraine headaches. There was a marked gender effect such that the relative odds for a woman with treated MDD to report migraine were over 5:1. Other associations were found between MDD and skin infections, respiratory illness, ulcer, hypotension, and diabetes. This is the largest non-patient sample using standardized assessment of mental disorders by direct interview in which associations between specific physical illnesses and MDD have been demonstrated. Implications for clinical practice and neurobiological research in depression are discussed. C1 WASHINGTON UNIV,SCH MED,DIV BIOSTAT,ST LOUIS,MO 63110. MALCOLM BLISS MENTAL HLTH CTR,ST LOUIS,MO. RUSH MED COLL,DEPT PSYCHIAT,CHICAGO,IL 60612. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. UNIV TEXAS,HLTH SCI CTR,DEPT PSYCHIAT,DALLAS,TX 75235. NIMH,OFF DIRECTOR,ROCKVILLE,MD 20857. RP MOLDIN, SO (reprint author), WASHINGTON UNIV,SCH MED,DEPT PSYCHIAT,4940 CHILDRENS PL,ST LOUIS,MO 63110, USA. FU NIMH NIH HHS [MH-25430, MH-46276, MH-48922] NR 30 TC 99 Z9 99 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD AUG PY 1993 VL 23 IS 3 BP 755 EP 761 PG 7 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA LX897 UT WOS:A1993LX89700022 PM 8234581 ER PT J AU POLAK, JF OLEARY, DH KRONMAL, RA WOLFSON, SK BOND, MG TRACY, RP GARDIN, JM KITTNER, SJ PRICE, TR SAVAGE, PJ AF POLAK, JF OLEARY, DH KRONMAL, RA WOLFSON, SK BOND, MG TRACY, RP GARDIN, JM KITTNER, SJ PRICE, TR SAVAGE, PJ TI SONOGRAPHIC EVALUATION OF CAROTID-ARTERY ATHEROSCLEROSIS IN THE ELDERLY - RELATIONSHIP OF DISEASE SEVERITY TO STROKE AND TRANSIENT ISCHEMIC ATTACK SO RADIOLOGY LA English DT Article DE CAROTID ARTERIES, STENOSIS OR OBSTRUCTION; CAROTID ARTERIES, US ID B-MODE ULTRASONOGRAPHY; CEREBRAL-ISCHEMIA; HIGH-RESOLUTION; PLAQUE; ULTRASOUND; BIFURCATION; STENOSIS; WALL; HEMORRHAGE; THICKNESS AB Doppler and real-time ultrasound (US) were performed to evaluate the extent of atherosclerotic changes in the carotid artery and to assess their relationship to prevalent cerebrovascular disease. Real-time US scans and Doppler measurements of the carotid arteries were analyzed in 5,201 subjects aged 65 years or older. Severity of atherosclerotic lesions was associated with increased frequencies of hyperechoic, irregular, and heterogeneous textured lesions (P < .0001). The severity of internal carotid artery stenosis was associated with thickening of the intima-media layer of the common carotid artery wall (r = .37, P < .0001). A history of stroke and transient ischemic attack (TIA) was more likely when hyperechoic, heterogeneous, and irregular lesions were seen in the carotid artery. Internal carotid artery stenosis correlated better with prevalent stroke and TIA than did sonographic descriptions of plaque texture. However, the prevalence of hyperechoic, heterogeneous, and irregular lesions increased as the degree of internal carotid stenosis increased. On real-time images alone, the average of the internal carotid artery maximal wall thickness is the sonographic measure of atherosclerosis that enables the best prediction of prevalent stroke and TIA. C1 BRIGHAM & WOMENS HOSP,DEPT RADIOL,BOSTON,MA 02115. GEISINGER MED CTR,DIV RADIOL,DANVILLE,PA 17822. UNIV PITTSBURGH,DEPT NEUROL SURG,PITTSBURGH,PA 15260. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC 27103. UNIV VERMONT,DEPT PATHOL,GLOUCESTER,VT. UNIV CALIF IRVINE,IRVINE MED CTR,DIV CARDIOL,ORANGE,CA 92668. UNIV MARYLAND,DEPT NEUROL,BALTIMORE,MD 21201. NIH,BETHESDA,MD 20892. RP POLAK, JF (reprint author), UNIV WASHINGTON,CHS COORDINATING CTR,1107 NE 45TH ST,RM 530,SEATTLE,WA 98105, USA. FU NHLBI NIH HHS [1-HC-85079-1-HC-85086] NR 31 TC 99 Z9 102 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD AUG PY 1993 VL 188 IS 2 BP 363 EP 370 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LM849 UT WOS:A1993LM84900013 PM 8327679 ER PT J AU SCHWARTZ, RH AF SCHWARTZ, RH TI T-CELL ANERGY SO SCIENTIFIC AMERICAN LA English DT Article ID CLONAL ANERGY RP SCHWARTZ, RH (reprint author), NIAID,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 5 TC 21 Z9 21 U1 0 U2 0 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 SN 0036-8733 J9 SCI AM JI Sci.Am. PD AUG PY 1993 VL 269 IS 2 BP 62 EP & PG 0 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LM920 UT WOS:A1993LM92000010 PM 8351512 ER PT J AU AKIYAMA, SK YAMADA, KM AF AKIYAMA, SK YAMADA, KM TI ADHESION MOLECULES IN CANCER .1. INTRODUCTION SO SEMINARS IN CANCER BIOLOGY LA English DT Editorial Material ID CELL-SURFACE RECEPTORS; METASTASIS; INTEGRINS; SITES RP AKIYAMA, SK (reprint author), NIDR,DEV BIOL LAB,BETHESDA,MD 20892, USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 12 TC 17 Z9 17 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD AUG PY 1993 VL 4 IS 4 BP 215 EP 218 PG 4 WC Oncology SC Oncology GA LR763 UT WOS:A1993LR76300001 PM 8400143 ER PT J AU YAMAMURA, K KIBBEY, MC JUN, SH KLEINMAN, HK AF YAMAMURA, K KIBBEY, MC JUN, SH KLEINMAN, HK TI EFFECT OF MATRIGEL AND LAMININ PEPTIDE YIGSR ON TUMOR-GROWTH AND METASTASIS SO SEMINARS IN CANCER BIOLOGY LA English DT Article DE SYNTHETIC PEPTIDE; TUMOR; METASTASIS; LAMININ; MATRIGEL ID BASEMENT-MEMBRANE MATRIGEL; HUMAN PROSTATIC-CARCINOMA; AMINO-ACID-SEQUENCE; A-CHAIN; EXTRACELLULAR-MATRIX; CELL-ADHESION; SYNTHETIC POLYPEPTIDES; MULTIDOMAIN PROTEIN; ENDOTHELIAL-CELLS; IV COLLAGENASE RP YAMAMURA, K (reprint author), NIDR,DEV BIOL LAB,BETHESDA,MD 20892, USA. NR 54 TC 35 Z9 36 U1 1 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD AUG PY 1993 VL 4 IS 4 BP 259 EP 265 PG 7 WC Oncology SC Oncology GA LR763 UT WOS:A1993LR76300006 PM 8400148 ER PT J AU ROWINSKY, EK EISENHAUER, EA CHAUDHRY, V ARBUCK, SG DONEHOWER, RC AF ROWINSKY, EK EISENHAUER, EA CHAUDHRY, V ARBUCK, SG DONEHOWER, RC TI CLINICAL TOXICITIES ENCOUNTERED WITH PACLITAXEL (TAXOL(R)) SO SEMINARS IN ONCOLOGY LA English DT Article ID PHASE-I TRIAL; HISTAMINE-RELEASE; INDUCED NEUROPATHY; CONTRAST-MEDIA; NERVE CRUSH; HEART; CANCER; INFUSION; AGENT; DRUG C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. QUEENS UNIV,CANADA CLIN TRIALS PROGRAM,NATL CANC INST,KINGSTON K7L 3N6,ONTARIO,CANADA. NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,INVESTIGAT DRUG BRANCH,BETHESDA,MD 20892. RP ROWINSKY, EK (reprint author), JOHNS HOPKINS ONCOL CTR,DIV PHARMACOL & EXPTL THERAPEUT,600 N WOLFE ST,BALTIMORE,MD 21287, USA. NR 58 TC 492 Z9 509 U1 3 U2 31 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD AUG PY 1993 VL 20 IS 4 SU 3 BP 1 EP 15 PG 15 WC Oncology SC Oncology GA LT571 UT WOS:A1993LT57100001 PM 8102012 ER PT J AU ARBUCK, SG CANETTA, R ONETTO, N CHRISTIAN, MC AF ARBUCK, SG CANETTA, R ONETTO, N CHRISTIAN, MC TI CURRENT DOSAGE AND SCHEDULE ISSUES IN THE DEVELOPMENT OF PACLITAXEL (TAXOL(R)) SO SEMINARS IN ONCOLOGY LA English DT Article ID PHASE-I TRIAL; EVERY 21 DAYS; INFUSION; CELLS; INVITRO; CANCER; NEUROPATHY; AGENT C1 BRISTOL MYERS SQUIBB,PHARMACEUT RES INST,CLIN CANC RES DEPT,WALLINGFORD,CT. RP ARBUCK, SG (reprint author), NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,INVESTIGAT DRUG BRANCH,BETHESDA,MD 20892, USA. NR 52 TC 66 Z9 66 U1 2 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD AUG PY 1993 VL 20 IS 4 SU 3 BP 31 EP 39 PG 9 WC Oncology SC Oncology GA LT571 UT WOS:A1993LT57100004 PM 8102016 ER PT J AU SEIDMAN, AD NORTON, L REICHMAN, BS CROWN, JPA YAO, TJ HEELAN, R HAKES, TB LEBWOHL, DE GILEWSKI, TA SURBONE, A CURRIE, V HUDIS, CA KLECKER, R JAMISDOW, C COLLINS, J QUINLIVAN, S BERKERY, R TOOMASI, F CANETTA, R FISHERMAN, J ARBUCK, S AF SEIDMAN, AD NORTON, L REICHMAN, BS CROWN, JPA YAO, TJ HEELAN, R HAKES, TB LEBWOHL, DE GILEWSKI, TA SURBONE, A CURRIE, V HUDIS, CA KLECKER, R JAMISDOW, C COLLINS, J QUINLIVAN, S BERKERY, R TOOMASI, F CANETTA, R FISHERMAN, J ARBUCK, S TI PRELIMINARY EXPERIENCE WITH PACLITAXEL (TAXOL(R)) PLUS RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR IN THE TREATMENT OF BREAST-CANCER SO SEMINARS IN ONCOLOGY LA English DT Article ID PHASE-I TRIAL; EVERY 21 DAYS; METASTATIC MELANOMA; RESISTANCE; AGENT; CELLS; DRUGS C1 US FDA,DIV CLIN PHARMACOL,ROCKVILLE,MD 20857. BRISTOL MYERS SQUIBB,PHARMACEUT RES INST,WALLINGFORD,CT. NCI,DIV CANC TREATMENT,INVESTIGAT DRUG BRANCH,BETHESDA,MD 20892. RP SEIDMAN, AD (reprint author), MEM SLOAN KETTERING CANC CTR,DEPT MED,DIV SOLID TUMOR ONCOL,HOWARD BLDG,ROOM 1009,1275 YORK AVE,NEW YORK,NY 10021, USA. FU NCI NIH HHS [CA-09207-14, 1-CM07311] NR 23 TC 64 Z9 64 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD AUG PY 1993 VL 20 IS 4 SU 3 BP 40 EP 45 PG 6 WC Oncology SC Oncology GA LT571 UT WOS:A1993LT57100005 PM 7688145 ER PT J AU SZABO, E BIRRER, MJ MULSHINE, JL AF SZABO, E BIRRER, MJ MULSHINE, JL TI EARLY DETECTION OF LUNG-CANCER SO SEMINARS IN ONCOLOGY LA English DT Article ID SMALL-CELL-CARCINOMA; K-RAS ONCOGENE; GASTRIN-RELEASING PEPTIDE; GROWTH-FACTORS; P53 MUTATIONS; MONOCLONAL-ANTIBODY; AUTOCRINE GROWTH; 3P DELETION; FOLLOW-UP; EXPRESSION RP NCI, DIV CANC PREVENT & CONTROL, BIOMARKERS & PREVENT RES BRANCH, 9610 MED CTR DR, ROOM 300, ROCKVILLE, MD 20850 USA. NR 89 TC 15 Z9 15 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0093-7754 EI 1532-8708 J9 SEMIN ONCOL JI Semin. Oncol. PD AUG PY 1993 VL 20 IS 4 BP 374 EP 382 PG 9 WC Oncology SC Oncology GA LT244 UT WOS:A1993LT24400011 PM 8342067 ER PT J AU CASSEDY, JH AF CASSEDY, JH TI MEDICAL JOURNALS AND MEDICAL KNOWLEDGE - HISTORICAL ESSAYS - BYNUM,WF, LOCK,S, PORTER,R SO SOCIAL HISTORY OF MEDICINE LA English DT Book Review RP CASSEDY, JH (reprint author), NATL LIB MED,BETHESDA,MD 20209, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0951-631X J9 SOC HIST MED JI Soc. Hist. Med. PD AUG PY 1993 VL 6 IS 2 BP 279 EP 280 DI 10.1093/shm/6.2.279 PG 2 WC History; History & Philosophy Of Science SC History; History & Philosophy of Science GA MA412 UT WOS:A1993MA41200009 ER PT J AU CHO, MJ MOSCICKI, EK NARROW, WE RAE, DS LOCKE, BZ REGIER, DA AF CHO, MJ MOSCICKI, EK NARROW, WE RAE, DS LOCKE, BZ REGIER, DA TI CONCORDANCE BETWEEN 2 MEASURES OF DEPRESSION IN THE HISPANIC HEALTH AND NUTRITION EXAMINATION SURVEY SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY LA English DT Article ID DIAGNOSTIC INTERVIEW SCHEDULE; CHARACTERISTIC ROC ANALYSIS; COMMUNITY SAMPLE; MENTAL-HEALTH; CES-D; GENERAL POPULATION; UNITED-STATES; SYMPTOMS; SYMPTOMATOLOGY; DISORDERS AB A concordance analysis between the Center for Epidemiologic Studies Depression Scale (CES-D) and the National Institute of Mental Health (NIMH) Diagnostic Interview Schedule (DIS) for current major depression was conducted using data from Cuban Americans and Puerto Rican respondents to the Hispanic Health and Nutrition Examination Survey (HHANES). Overall agreement between the two depression measures was relatively high, which suggested that the CES-D might be appropriate as a first-stage screening instrument for community-based surveys of clinical depression. Female gender and indicators of social class (education, income, poverty index, and employment) were related to low specificity and low agreement. The estimated cutoff points of the CES-D that best predicted DIS current major depression were different between the two ethnic groups; 17 for Cuban Americans, and 20 for Puerto Ricans. A receiver operating characteristics (ROC) curve analysis revealed that the traditional method of defining CES-D cases by summing the scores for each item was superior to counting only the persistent symptoms, that is, those present nearly everyday. C1 NIMH,DIV EPIDEMIOL & SERV RES,PREVENT RES BRANCH,ROOM 10-85,ROCKVILLE,MD 20857. FU ADAMHA HHS [RA-ADM-81-1] NR 64 TC 60 Z9 60 U1 3 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0933-7954 J9 SOC PSYCH PSYCH EPID JI Soc. Psychiatry Psychiatr. Epidemiol. PD AUG PY 1993 VL 28 IS 4 BP 156 EP 163 DI 10.1007/BF00797317 PG 8 WC Psychiatry SC Psychiatry GA LV865 UT WOS:A1993LV86500002 PM 8235801 ER PT J AU SPIEGELHALTER, DJ FREEDMAN, LS PARMAR, MKB AF SPIEGELHALTER, DJ FREEDMAN, LS PARMAR, MKB TI APPLYING BAYESIAN IDEAS IN DRUG DEVELOPMENT AND CLINICAL-TRIALS SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT CONF ON METHODOLOGICAL AND ETHICAL ISSUES IN CLINICAL TRIALS CY JUN 27-28, 1991 CL LONDON, ENGLAND SP LONDON SCH ECON CTR PHILOS NAT & SOCIAL SCI, ROYAL STAT SOC, MED SECT, MIND ASSOC, WELCOME TRUST, CIBA GEIGY, ECON & SOCIAL RES COUNCIL, ANAL COMM ID OPINION AB The Bayesian paradigm emphasizes that studies are not performed in isolation, and that external evidence can be used formally in the design, monitoring and reporting of clinical trials. A variety of tools for assessing the current evidence for treatment efficacy are presented, making use of graphical display to provide insight into ethical and efficiency issues in starting and stopping trials - these are illustrated with a trial in osteosarcoma that is currently taking place. Finally we recommend that an additional 'interpretation' section is placed in clinical reports to provide a bridge between 'results' and 'discussion' - it is this section that would contain the Bayesian perspective. C1 NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,BETHESDA,MD 20892. MRC,CANC TRIALS OFF,CAMBRIDGE CB2 2BB,ENGLAND. RP SPIEGELHALTER, DJ (reprint author), INST PUBL HLTH,MRC,BIOSTAT UNIT,ROBINSON WAY,CAMBRIDGE CB2 2SR,ENGLAND. NR 16 TC 62 Z9 62 U1 0 U2 7 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD AUG PY 1993 VL 12 IS 15-16 BP 1501 EP 1511 DI 10.1002/sim.4780121516 PG 11 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA LV114 UT WOS:A1993LV11400014 PM 8248659 ER PT J AU WEHRLI, SL MOORE, KS RODER, H DURELL, S ZASLOFF, M AF WEHRLI, SL MOORE, KS RODER, H DURELL, S ZASLOFF, M TI STRUCTURE OF THE NOVEL STEROIDAL ANTIBIOTIC SQUALAMINE DETERMINED BY 2-DIMENSIONAL NMR-SPECTROSCOPY SO STEROIDS LA English DT Article DE STEROL; SPERMIDINE; ANTIMICROBIAL; ANTIBACTERIAL; NMR SPECTROSCOPY; SHARK ID MULTIPLE QUANTUM NMR; ANTIBACTERIAL PEPTIDES; ANTIMICROBIAL PEPTIDES; POLARIZATION TRANSFER; COHERENCE-TRANSFER; PIG INTESTINE; SPECTRA; PROTON; CELLS; SKIN AB Squalamine is a novel aminosterol recently isolated from the dogfish shark, Squalus acanthias. This water-soluble steroid exhibits potent antibacterial activity against both gram-negative and gram-positive bacteria. In addition, squalamine is fungicidal and induces osmotic lysis of protozoa. We report here the structural determination of squalamine, 3beta-N-1-[N(3-[4-aminobutyl])-1,3 diaminopropane]-7alpha,24zeta-dihydroxy-5alpha-cholestane 24-sulfate, which was deduced from the analysis of fast atom bombardment spectra and a series of two-dimensional nuclear magnetic resonance (NMR) spectra. Squalamine is a cationic steroid characterized by a condensation of an anionic bile salt intermediate with the polyamine, spermidine. This molecule is a potential host-defense agent in the shark, and provides insight into a new class of vertebrate antimicrobial molecules. C1 CHILDRENS HOSP PHILADELPHIA,DIV BIOCHEM DEV & MOLEC DIS,PHILADELPHIA,PA. CHILDRENS HOSP PHILADELPHIA,DIV HUMAN GENET & MOLEC BIOL,PHILADELPHIA,PA. UNIV PENN,SCH MED,DEPT BIOCHEM & BIOPHYS,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT GENET,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT PEDIAT,PHILADELPHIA,PA 19104. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. NCI,MATH BIOL LAB,BETHESDA,MD 20892. RI Roder, Heinrich/B-3455-2009 OI Roder, Heinrich/0000-0003-1860-2491 FU NIGMS NIH HHS [5T32GM07170] NR 39 TC 61 Z9 65 U1 3 U2 16 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0039-128X J9 STEROIDS JI Steroids PD AUG PY 1993 VL 58 IS 8 BP 370 EP 378 DI 10.1016/0039-128X(93)90040-T PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA LR464 UT WOS:A1993LR46400005 PM 8212087 ER PT J AU ZEIGER, MA NORTON, JA AF ZEIGER, MA NORTON, JA TI GSALPHA - IDENTIFICATION OF A GENE HIGHLY EXPRESSED BY INSULINOMA AND OTHER ENDOCRINE TUMORS SO SURGERY LA English DT Article; Proceedings Paper CT 54TH ANNUAL MEETING OF THE SOC OF UNIVERSITY SURGEONS CY FEB 11-13, 1992 CL SEATTLE, WA SP SOC UNIV SURGEONS ID G-PROTEIN; PC12 CELLS; MUTATIONS; DIFFERENTIATION; MICROINJECTION; SUBTRACTION; ONCOGENES; NEOPLASIA; CYCLASE; MICE AB Background. The isolation of mRNA molecules that are either uniquely or more highly expressed by tumor and not normal tissue is a powerful tool in the study of cell regulation and growth. To this end we constructed a complementary DNA (cDNA) library from messenger RNA (mRNA) isolated from a human insulinoma and, by differential hybridization with cDNA from both normal pancreas and insulinoma, isolated clones more highly expressed by insulinoma. Methods. Total RNA was isolated from human insulinoma and normal pancreas and purified to mRNA by oligo (dT) column. An insulinoma cDNA library was constructed and screened with P-32-labeled cDNA from pancreas and insulinoma. Northern blots from insulinoma, pancreas, carcinomas, normal endocrine tissues, and endocrine tumors were then probed with the P-32-labeled inserts. Results. Two clones that consistently hybridized with P-32 cDNA from insulinoma and not pancreas proved to represent mRNAs for insulin and the alpha subunit of the G(s) protein. There was a markedly higher expression (30-fold) of the gene for G(s)alpha in mRNA from insulinoma compared with normal pancreas by Northern blot analysis. We found Gs(alpha) to be more highly expressed by a pheochromocytoma, a corticotropin-producing islet cell tumor of the pancreas, and a corticotropin-producing thymic carcinoid (up to 35-fold) compared with normal pancreas, whereas normal endocrine tissues, a parathyroid adenoma, thyroid follicular adenoma, gastrinoma, and several carcinomas showed no expression. Conclusions. This study showed that G(s)alpha is highly expressed in insulinoma and certain endocrine tumors. It is not expressed in several cancers or normal endocrine tissues. Others have implicated mutated G(s) proteins in the tumorigenesis of pituitary and thyroid tumors. G proteins are also known to mediate hormonal transmembrane signaling. Its overexpression in four of seven endocrine tumors tested suggests that it may have a role in the unregulated hormone secretion and/or a role in the tumorigenesis of differentiated endocrine tumors. RP ZEIGER, MA (reprint author), NCI,SURG BRANCH,METAB SECT,ROOM 2B01,BLDG 10,BETHESDA,MD 20892, USA. NR 21 TC 12 Z9 12 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 AUG PY 1993 VL 114 IS 2 BP 458 EP 463 PG 6 WC Surgery SC Surgery GA LQ384 UT WOS:A1993LQ38400042 PM 8342148 ER PT J AU POGREBNIAK, HW LUBENSKY, IA PASS, HI AF POGREBNIAK, HW LUBENSKY, IA PASS, HI TI DIFFERENTIAL EXPRESSION OF PLATELET-DERIVED GROWTH-FACTOR-BETA IN MALIGNANT MESOTHELIOMA - A CLUE TO FUTURE THERAPIES SO SURGICAL ONCOLOGY-OXFORD LA English DT Article DE MESOTHELIOMA; NORTHERN BLOT; PDGF-BETA; RNA AB Malignant mesothelioma (MM) is resistant to most standard forms of treatment. Accordingly, novel therapies based on the genetic and autocrine growth characteristics are being investigated. Platelet-derived growth factor (PDGF). a potent mitogen for mesenchymal cells, is produced by several human malignant cell lines including MM and therefore may promote tumourigenesis by an autocrine mechanism. We investigated the expression of PDGF-beta mRMA in tumour specimens excised from 18 patients with MM. Total cellular RNA was successfully extracted from 16/18 frozen tumour specimens with guanidine isothiocyanate and purified by centrifugation through a caesium chloride gradient. Northern blots were prepared and probed sequentially with P-32-labelled PDGF-beta and beta-actin cDNA. Gene expression was quantitated by optical densitometry. Freshly elutriated human peripheral blood monocytes were stimulated to induce PDGF-mRNA expression with transforming growth factor-beta-1. This positive control was assigned an expression index (EI) of 1, with the EI for the tumour sample calculated as: PDGF(patient)/Actin(patient)/EI positive control. In the 16 tumour specimens with useable RNA, transcripts for PDGF-beta MRNA were detected. Northern blot analyses revealed elevation of PDGF-beta expression above control in 10/16 (63%) of MM patients. A 230% increase in PDGF-beta expression (EI=1.62 vs. EI=0.49) was found between the lowest and highest expression samples. The specimens from which the PDGF transcripts were derived were found histologically to contain 87% tumour and 13% contaminating normal cells, predominantly lymphocytes. The elucidation of the transcriptional regulation of growth factors which are implicated in the pathogenesis of MM may guide the development of more effective biologic therapies. C1 NCI,SURG BRANCH,THORAC ONCOL SECT,BETHESDA,MD 20892. NR 0 TC 12 Z9 12 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0960-7404 J9 SURG ONCOL JI Surg. Oncol.-Oxf. PD AUG PY 1993 VL 2 IS 4 BP 235 EP 240 DI 10.1016/0960-7404(93)90012-N PG 6 WC Oncology; Surgery SC Oncology; Surgery GA MH347 UT WOS:A1993MH34700003 PM 8252214 ER PT J AU GRESS, RE KATZ, SI LUCAS, PJ AF GRESS, RE KATZ, SI LUCAS, PJ TI HUMAN CD8+ XENOREACTIVE T-CELLS MEDIATE TISSUE-INJURY IN-VIVO SO TRANSPLANTATION LA English DT Note ID EFFECTOR MECHANISM; TRANSPLANTATION; SPECIFICITY; REJECTION; MARROW RP GRESS, RE (reprint author), NCI,EXPTL IMMUNOL BRANCH,DERMATOL BRANCH,BLDG 10,ROOM 4B17,BETHESDA,MD 20892, USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD AUG PY 1993 VL 56 IS 2 BP 484 EP 486 DI 10.1097/00007890-199308000-00049 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA LT250 UT WOS:A1993LT25000049 PM 7689266 ER PT J AU ZACHARY, AA AF ZACHARY, AA TI THE GENETICS OF RACE SO TRANSPLANTATION PROCEEDINGS LA English DT Article RP ZACHARY, AA (reprint author), NIAID,SOLAR BLDG ROOM 4 A13,6003 EXECUT BLVD,ROCKVILLE,MD 20852, USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD AUG PY 1993 VL 25 IS 4 BP 2397 EP 2397 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA LR872 UT WOS:A1993LR87200003 PM 8356611 ER PT J AU KAUFMAN, BT AF KAUFMAN, BT TI WHY NADP SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Editorial Material RP KAUFMAN, BT (reprint author), NIH,BLDG 6,RM B1-05,BETHESDA,MD 20892, USA. NR 3 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 AUG PY 1993 VL 18 IS 8 BP 278 EP 278 DI 10.1016/0968-0004(93)90033-J PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LR630 UT WOS:A1993LR63000003 PM 8236437 ER PT J AU RIVAS, G MINTON, AP AF RIVAS, G MINTON, AP TI NEW DEVELOPMENTS IN THE STUDY OF BIOMOLECULAR ASSOCIATIONS VIA SEDIMENTATION EQUILIBRIUM SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID SELF-ASSOCIATION; ANALYTICAL ULTRACENTRIFUGATION; ANALYTICAL CENTRIFUGATION; PROTEIN INTERACTIONS; ULTRA-CENTRIFUGE; BINDING; ACTIN; CA2+ AB The measurement and analysis of sedimentation equilibrium provide one of the most powerful techniques for quantitative characterization of reversible and irreversible macromolecular associations in solution. The use of this technique by nonspecialists has been greatly helped in recent years by the development of new instrumentation, new types of experiments and new PC-based software for computer-aided analysis of experimental results. C1 NIDDKD, BIOCHEM PHARMACOL LAB, BETHESDA, MD 20814 USA. RP UNIV BASEL, BIOCTR, DEPT BIOPHYS CHEM, KLINGELBERGSTR 70, CH-4056 BASEL, SWITZERLAND. OI Rivas, German/0000-0003-3450-7478 NR 37 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD AUG PY 1993 VL 18 IS 8 BP 284 EP 287 DI 10.1016/0968-0004(93)90035-L PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LR630 UT WOS:A1993LR63000005 PM 8236439 ER PT J AU WISTOW, G AF WISTOW, G TI LENS CRYSTALLINS - GENE RECRUITMENT AND EVOLUTIONARY DYNAMISM SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID ALPHA-B-CRYSTALLIN; GUINEA-PIG LENS; EYE LENS; ARGININOSUCCINATE LYASE; STRUCTURAL PROTEIN; ZETA-CRYSTALLIN; C-MYC; EXPRESSION; CELLS; DELTA-2-CRYSTALLIN AB In a novel evolutionary process. enzymes and stress proteins have undergone direct gene recruitment as eye lens crystallins in a number of independent events. This may have allowed a dynamic response to changing visual environments during evolution. In spite of their diversity, many crystallins may share an origin in essential developmental processes such as cell elongation. RP WISTOW, G (reprint author), NEI,LMDB,MOLEC STRUCT & FUNCT SECT,BETHESDA,MD 20892, USA. NR 41 TC 197 Z9 200 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 AUG PY 1993 VL 18 IS 8 BP 301 EP 306 DI 10.1016/0968-0004(93)90041-K PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LR630 UT WOS:A1993LR63000011 PM 8236445 ER PT J AU BENVENGA, S ROBBINS, J AF BENVENGA, S ROBBINS, J TI LIPOPROTEIN THYROID-HORMONE INTERACTIONS SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID LOW-DENSITY LIPOPROTEIN; APOLIPOPROTEIN-A-I; PLASMA-LIPOPROTEINS; GENE-EXPRESSION; LDL RECEPTOR; BINDING; THYROXINE; CELLS; FIBROBLASTS; DOMAIN AB A small but significant portion of the thyroid hormones that circulate in human plasma is associated with lipoproteins. Although the major lipoprotein carrier is HDL, the role of these interactions on T4 entry into cells was tested first with LDL and human fibroblasts because of the well-characterized LDL receptors and the availability of cells with genetically absent receptors. It was shown that LDL enhanced the uptake of T4 by cultured fibroblasts in which the LDL receptors were expressed. The T4-binding sites on apolipoproteins B-100 and E, as well as apoA-I, have been partially characterized, and they exhibit considerable homology. A number of possible physiologic consequences of thyroid hormone-lipoprotein interactions have been put forward as topics for further investigation. C1 NATL INST DIABET & DIGEST & KIDNEY DIS,GENET & BIOCHEM BRANCH,BETHESDA,MD 20892. RP BENVENGA, S (reprint author), UNIV MESSINA,SCH MED,ENDOCRINOL SECT,I-98100 MESSINA,ITALY. NR 28 TC 20 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD AUG PY 1993 VL 4 IS 6 BP 194 EP 198 DI 10.1016/1043-2760(93)90116-V PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LX749 UT WOS:A1993LX74900003 PM 18407156 ER PT J AU STEINERT, PM BALE, SJ AF STEINERT, PM BALE, SJ TI GENETIC SKIN DISEASES CAUSED BY MUTATIONS IN KERATIN INTERMEDIATE FILAMENTS SO TRENDS IN GENETICS LA English DT Review ID EPIDERMOLYTIC HYPERKERATOSIS; BULLOSA; INVITRO; NETWORKS; LINKAGE; CLUSTER; PHOSPHORYLATION; CHROMOSOME-12; PEPTIDE; REGION AB Keratin intermediate filaments are the major differentiation products of epithelial cells such as the epidermis. The filaments are highly dynamic entities involved in the maintenance of the structural integrity of both the individual cells and the entire tissue. Recent biochemical studies suggest that the keratin proteins overlap each other in several key locations when packed together in filaments. Interestingly, mutations that introduce inappropriate amino acid substitutions in at least some of these overlap regions cause defective keratin filaments that result in at least three classes of autosomal dominant skin disease. RP STEINERT, PM (reprint author), NIAMSD,SKIN BIOL BRANCH,BLDG 6,ROOM 425,BETHESDA,MD 20892, USA. NR 44 TC 60 Z9 60 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD AUG PY 1993 VL 9 IS 8 BP 280 EP 284 DI 10.1016/0168-9525(93)90014-9 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA LN542 UT WOS:A1993LN54200007 PM 7691000 ER PT J AU WESS, J AF WESS, J TI MOLECULAR-BASIS OF MUSCARINIC ACETYLCHOLINE-RECEPTOR FUNCTION SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID SITE-DIRECTED MUTAGENESIS; BETA-ADRENERGIC-RECEPTOR; 3RD CYTOPLASMIC LOOP; PROTEIN-COUPLED RECEPTORS; LIGAND-BINDING; CHOLINERGIC RECEPTOR; ANTAGONIST BINDING; TYROSINE RESIDUES; STRUCTURAL BASIS; AMINO-ACIDS AB Muscarinic acetylcholine receptors play important roles in numerous physiological functions including higher cognitive processes such as memory and learning. Consistent with the well-documented pharmacological heterogeneity of muscarinic receptors, molecular cloning studies have revealed the existence of five distinct muscarinic receptor proteins (M1-M5). Structure-function relationship studies of the cloned receptors have been greatly aided by the high degree of structural homology that muscarinic receptors share with other G protein-coupled receptors. In this review, Jurgen Wess discusses recent mutagenesis studies that have considerably advanced our knowledge of the molecular details underlying muscarinic receptor function. RP WESS, J (reprint author), NIDDKD,BIOORGAN CHEM LAB,BLDG 8A,RM B1A-09,BETHESDA,MD 20892, USA. NR 45 TC 167 Z9 173 U1 1 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD AUG PY 1993 VL 14 IS 8 BP 308 EP 313 DI 10.1016/0165-6147(93)90049-P PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LW049 UT WOS:A1993LW04900009 PM 8249149 ER PT J AU SU, H CALDWELL, HD AF SU, H CALDWELL, HD TI IMMUNOGENICITY OF A SYNTHETIC OLIGOPEPTIDE CORRESPONDING TO ANTIGENICALLY COMMON T-HELPER AND B-CELL NEUTRALIZING EPITOPES OF THE MAJOR OUTER-MEMBRANE PROTEIN OF CHLAMYDIA-TRACHOMATIS SO VACCINE LA English DT Article DE CHLAMYDIA-TRACHOMATIS; MAJOR OUTER MEMBRANE PROTEIN; OLIGOPEPTIDE; IMMUNOGENICITY ID PROTECTIVE MONOCLONAL-ANTIBODIES; NUCLEOTIDE-SEQUENCE; LYMPHOGRANULOMA-VENEREUM; INVITRO NEUTRALIZATION; PEPTIDE-SYNTHESIS; VIBRIO-CHOLERAE; AMINO-ACID; GENE; SUBUNIT; MICROSPHERES AB Sexually transmitted diseases (STDs) caused by Chlamydia trachomatis are an important public health problem and a vaccine to prevent or control these diseases is badly needed. The major outer membrane protein (MOMP) is the principal candidate antigen for the development of subunit vaccine against chlamydial STDs. The immunogenicity of a synthetic oligopeptide, termed A8-VDIV, corresponding to MOMP sequences containing both C. trachomatis species common T-helper (A8) and B-cell (VDIV) epitopes was studied in mice and non-human primates. Six of eight H-2 congenic mouse strains immunized with peptide A8-VDIV produced high-litre IgG antibodies against the VDIV B-cell portion of the oligopeptide. Fine mapping of the anti-peptide antibodies by pepscan ELISA showed that each of the responding mouse strains made antibodies reactive with a species-common septmeric neutralizing epitope 298LNPTIAG304 contained in the VDIV sequence. The mouse anti-peptide.antibodies reacted with intact C. trachomatis elementary bodies (EBs) by ELISA and neutralized chlamydial infectivity for cultured eukaryotic celLs with sub-species specificity. Three cynomolgus monkeys were immunized with peptide A8-VDIV and their IgG antibody responses were similarly studied. All three monkeys produced IgG antibodies which reacted with the VDIV peptide and which recognized the species-common LNPTIAG neutralizing site within the VDIV sequence. Monkey anti-peptide antibodies bound to intact C. trachomatis EBs and were neutralizing in vitro. The immunogeniciity of peptide A8-VDIV in different strains of mice disparate at H-2, its immunogenicity in non-human primates, and its ability to target cross-reactive neutralizing antibody responses against multiple C. trachomatis serovars are encouraging findings in terms of the potential utility of the oligopeptide as an experimental vaccine against chlamydial STDs. C1 NIAID,INTRACELLULAR PARASITES LAB,ROCKY MT LABS,HAMILTON,MT 59840. NR 34 TC 26 Z9 26 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD AUG PY 1993 VL 11 IS 11 BP 1159 EP 1166 DI 10.1016/0264-410X(93)90080-H PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA LV899 UT WOS:A1993LV89900015 PM 7504381 ER PT J AU OSTLUND, EN AF OSTLUND, EN TI THE EQUINE HERPESVIRUSES SO VETERINARY CLINICS OF NORTH AMERICA-EQUINE PRACTICE LA English DT Article RP OSTLUND, EN (reprint author), NIAID,INFECT DIS LAB,BLDG 7,ROOM 100,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 53 Z9 57 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0749-0739 J9 VET CLIN N AM-EQUINE JI Vet. Clin. N. Am.-Equine Pract. PD AUG PY 1993 VL 9 IS 2 BP 283 EP 294 PG 12 WC Veterinary Sciences SC Veterinary Sciences GA LN372 UT WOS:A1993LN37200004 PM 8395324 ER PT J AU MACIEJEWSKI, JP BRUENING, EE DONAHUE, RE SELLERS, SE CARTER, C YOUNG, NS STJEOR, S AF MACIEJEWSKI, JP BRUENING, EE DONAHUE, RE SELLERS, SE CARTER, C YOUNG, NS STJEOR, S TI INFECTION OF MONONUCLEATED PHAGOCYTES WITH HUMAN CYTOMEGALOVIRUS SO VIROLOGY LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; IMMEDIATE-EARLY GENE; BONE-MARROW-CELLS; VIRUS INFECTION; IMMUNOSUPPRESSION; MONOCYTE; TRANSPLANTATION; EXPRESSION; INTERLEUKIN-1; MACROPHAGES C1 UNIV NEVADA,DEPT MICROBIOL,RENO,NV 89557. NHLBI,CLIN HEMATOL BRANCH,CELL BIOL SECT,BETHESDA,MD 20892. NIH,CTR CLIN,DIV TRANSFUS MED,BETHESDA,MD 20892. FU NHLBI NIH HHS [HL48503] NR 42 TC 50 Z9 51 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD AUG PY 1993 VL 195 IS 2 BP 327 EP 336 DI 10.1006/viro.1993.1383 PG 10 WC Virology SC Virology GA LM714 UT WOS:A1993LM71400003 PM 8393230 ER PT J AU CONNOR, LM OXMAN, MN BRADY, JN MARRIOTT, SJ AF CONNOR, LM OXMAN, MN BRADY, JN MARRIOTT, SJ TI 21 BASE-PAIR REPEAT ELEMENTS INFLUENCE THE ABILITY OF A GAL4-TAX FUSION PROTEIN TO TRANSACTIVATE THE HTLV-I LONG TERMINAL REPEAT SO VIROLOGY LA English DT Article ID T-CELL LEUKEMIA; VIRUS TYPE-I; TROPICAL SPASTIC PARAPARESIS; TRANSCRIPTIONAL ACTIVATION; ADENOVIRUS-E1A PROTEIN; RESPONSIVE ELEMENT; TRANS-ACTIVATION; ENHANCER ELEMENT; MAMMALIAN-CELLS; GENE-EXPRESSION C1 BAYLOR COLL MED,DIV MOLEC VIROL,1 BAYLOR PLAZA,HOUSTON,TX 77030. NCI,MOLEC VIROL LAB,BALTIMORE,MD 21211. FU NCI NIH HHS [1R01CA55684-01] NR 59 TC 22 Z9 22 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD AUG PY 1993 VL 195 IS 2 BP 569 EP 577 DI 10.1006/viro.1993.1408 PG 9 WC Virology SC Virology GA LM714 UT WOS:A1993LM71400028 PM 8337832 ER PT J AU BOERKOEL, CF FEDERSPIEL, MJ SALTER, DW PAYNE, W CRITTENDEN, LB KUNG, HJ HUGHES, SH AF BOERKOEL, CF FEDERSPIEL, MJ SALTER, DW PAYNE, W CRITTENDEN, LB KUNG, HJ HUGHES, SH TI A NEW DEFECTIVE RETROVIRAL VECTOR SYSTEM BASED ON THE BRYAN STRAIN OF ROUS-SARCOMA VIRUS SO VIROLOGY LA English DT Article ID HEMATOPOIETIC STEM-CELLS; CHICKEN OPTIC TECTUM; HIGH-TITER STRAIN; OWN GENOMIC RNA; GENE-TRANSFER; GERM LINE; RETICULOENDOTHELIOSIS VIRUSES; TRANSCRIPTIONAL INTERFERENCE; RECOMBINANT RETROVIRUS; COMPETENT VIRUS C1 NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,BLDG 539,POB B,FREDERICK,MD 21702. CASE WESTERN RESERVE UNIV,SCH MED,DEPT MOLEC BIOL & MICROBIOL,CLEVELAND,OH 44106. MICHIGAN STATE UNIV,DEPT MICROBIOL,E LANSING,MI 48824. RI Kung, Hsing-Jien/C-7651-2013 FU NCI NIH HHS [CA 39207, CA 46613, N01-CO-74101] NR 87 TC 36 Z9 39 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD AUG PY 1993 VL 195 IS 2 BP 669 EP 679 DI 10.1006/viro.1993.1418 PG 11 WC Virology SC Virology GA LM714 UT WOS:A1993LM71400038 PM 8393241 ER PT J AU YUWEN, H COX, JH YEWDELL, JW BENNINK Jr MOSS, B AF YUWEN, H COX, JH YEWDELL, JW BENNINK, JR MOSS, B TI NUCLEAR-LOCALIZATION OF A DOUBLE-STRANDED RNA-BINDING PROTEIN ENCODED BY THE VACCINIA VIRUS E3L GENE SO VIROLOGY LA English DT Article ID INVADING INOCULUM PARTICLE; CELL-FREE TRANSLATION; POLYMERASE-II; NUCLEOTIDE-SEQUENCE; MESSENGER-RNAS; ALPHA-AMANITIN; DNA; HOST; REPLICATION; POXVIRUSES C1 NIAID, VIRAL DIS LAB, BETHESDA, MD 20892 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012; OI Cox, Josephine/0000-0003-1301-7373 NR 38 TC 107 Z9 107 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 0042-6822 J9 VIROLOGY JI Virology PD AUG PY 1993 VL 195 IS 2 BP 732 EP 744 DI 10.1006/viro.1993.1424 PG 13 WC Virology SC Virology GA LM714 UT WOS:A1993LM71400044 PM 8337842 ER PT J AU PURI, A KRUMBIEGEL, M DIMITROV, D BLUMENTHAL, R AF PURI, A KRUMBIEGEL, M DIMITROV, D BLUMENTHAL, R TI A NEW APPROACH TO MEASURE FUSION ACTIVITY OF CLONED VIRAL ENVELOPE PROTEINS - FLUORESCENCE DEQUENCHING OF OCTADECYLRHODAMINE-LABELED PLASMA-MEMBRANE VESICLES FUSING WITH CELLS EXPRESSING VESICULAR STOMATITIS-VIRUS GLYCOPROTEIN SO VIROLOGY LA English DT Note ID PH-DEPENDENT FUSION; KINETICS; MUTANT C1 NCI,MEMBRANE STRUCT & FUNCT SECT,BLDG 10,RM 4A01,BETHESDA,MD 20892. NR 14 TC 10 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD AUG PY 1993 VL 195 IS 2 BP 855 EP 858 DI 10.1006/viro.1993.1444 PG 4 WC Virology SC Virology GA LM714 UT WOS:A1993LM71400064 PM 8393251 ER PT J AU ERICKSON, FL HANNIG, EM KRASINSKAS, A KAHN, RA AF ERICKSON, FL HANNIG, EM KRASINSKAS, A KAHN, RA TI CLONING AND SEQUENCE OF ADP-RIBOSYLATION FACTOR-I (ARF1) FROM SCHIZOSACCHAROMYCES-POMBE SO YEAST LA English DT Article DE ADP-RIBOSYLATION FACTORS; GTP-BINDING PROTEINS; SACCHAROMYCES-CEREVISIAE; 3-AMNIOTRIAZOLE ID GTP-BINDING PROTEINS; SACCHAROMYCES-CEREVISIAE; TRANSLATIONAL ACTIVATOR; GCN4 AB A gene encoding a homologue of the ADP-ribosylation factor (ARF) family of small GTP binding proteins was cloned from a Schizosaccharomyces pombe cDNA library by a functional screen of suppressors of sensitivity to 3-aminotriazole in a gcn3 null strain of Saccharomyces cerevisiae. Two independent isolates each contained the full coding region of the ARF1 gene. The encoded SpARF1 protein has a predicted molecular weight of 20618 and is 88% and 79% identical to human and S. cerevisiae ARF1 proteins, respectively. As independent isolates were obtained, this effect of the SpARF1 appears to be a real phenomenon, but cannot currently be easily understood within the context of the evidence for a role(s) for ARF proteins in the protein secretory pathway. C1 NIH,DIV CANC INST,REGULATORY MECHANISMS SECT,BIOL CHEM LAB,BETHESDA,MD 20892. UNIV TEXAS,DEPT MOLEC & CELL BIOL,RICHARDSON,TX 75083. FU NCRR NIH HHS [2 S07 RR07733] NR 16 TC 7 Z9 8 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0749-503X J9 YEAST JI Yeast PD AUG PY 1993 VL 9 IS 8 BP 923 EP 927 DI 10.1002/yea.320090812 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA LV122 UT WOS:A1993LV12200011 PM 8212899 ER PT J AU MATSUMOTO, Y WICKNER, RB AF MATSUMOTO, Y WICKNER, RB TI CLG1, A NEW CYCLIN-LIKE GENE OF SACCHAROMYCES-CEREVISIAE SO YEAST LA English DT Article DE SK18; CELL CYCLE; SEQUENCE ID YEAST; ACTIVATION; HOMOLOG; MITOSIS; FAMILY; CDC28; PHASE; CLN2 AB A region of chromosome VII adjacent to SK18 has a 453 amino acid open reading frame whose sequence has significant similarity to that of HCS26, a G1 cyclin. A disruption mutation of this open reading frame has no apparent phenotype under the conditions tested. ORFD, an open reading frame adjacent to the CDC48 gene, is even more similar to HCS26. C1 NIDDKD,GENET SIMPLE EUKARYOTES SECT,BIOCHEM PHARMACOL LAB,BLDG 8,ROOM 207,BETHESDA,MD 20892. NR 15 TC 7 Z9 8 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0749-503X J9 YEAST JI Yeast PD AUG PY 1993 VL 9 IS 8 BP 929 EP 931 DI 10.1002/yea.320090813 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Microbiology; Mycology GA LV122 UT WOS:A1993LV12200012 PM 8212900 ER PT J AU JI, H SANDBERG, K ZHANG, Y CATT, KJ AF JI, H SANDBERG, K ZHANG, Y CATT, KJ TI MOLECULAR-CLONING, SEQUENCING AND FUNCTIONAL EXPRESSION OF AN AMPHIBIAN ANGIOTENSIN-II RECEPTOR SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID XENOPUS-LAEVIS OOCYTES; TYPE-1 RECEPTOR; CALCIUM MOBILIZATION; ANTAGONISTS; SUBTYPES; BOVINE; CDNA RP JI, H (reprint author), NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892, USA. NR 18 TC 63 Z9 65 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 JUL 30 PY 1993 VL 194 IS 2 BP 756 EP 762 DI 10.1006/bbrc.1993.1886 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LP969 UT WOS:A1993LP96900025 PM 7688227 ER PT J AU DEWEERTH, A PISEGNA, JR HUPPI, K WANK, SA AF DEWEERTH, A PISEGNA, JR HUPPI, K WANK, SA TI MOLECULAR-CLONING, FUNCTIONAL EXPRESSION AND CHROMOSOMAL LOCALIZATION OF THE HUMAN CHOLECYSTOKININ TYPE-A RECEPTOR SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID BETA-ADRENERGIC-RECEPTOR; SMOOTH-MUSCLE TUMORS; BIOCHEMICAL-CHARACTERIZATION; STRUCTURAL FEATURES; BOVINE RHODOPSIN; CCK RECEPTORS; GALLBLADDER; PROTEIN; ANTAGONIST; PANCREAS C1 NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892. NCI,GENET LAB,MOLEC GENET SECT,BETHESDA,MD 20892. NR 43 TC 132 Z9 132 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 30 PY 1993 VL 194 IS 2 BP 811 EP 818 DI 10.1006/bbrc.1993.1894 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LP969 UT WOS:A1993LP96900033 PM 8343165 ER PT J AU IMAMICHI, T UCHIDA, I WAHL, SM MCCARTNEYFRANCIS, N AF IMAMICHI, T UCHIDA, I WAHL, SM MCCARTNEYFRANCIS, N TI EXPRESSION AND CLONING OF MIGRATION-INHIBITORY FACTOR-RELATED PROTEIN-(MRP)8 AND PROTEIN-MRP14 IN ARTHRITIS-SUSCEPTIBLE RATS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CALCIUM-BINDING PROTEINS; CYSTIC-FIBROSIS ANTIGEN; EXTRACTION; TISSUES; GENE RP IMAMICHI, T (reprint author), NIDR,IMMUNOL LAB,CELLULAR IMMUNOL SECT,BETHESDA,MD 20892, USA. NR 22 TC 22 Z9 24 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 JUL 30 PY 1993 VL 194 IS 2 BP 819 EP 825 DI 10.1006/bbrc.1993.1895 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LP969 UT WOS:A1993LP96900034 PM 8343166 ER PT J AU JANG, JJ HENNEMAN, JR KURATA, Y UNO, H WARD, JM AF JANG, JJ HENNEMAN, JR KURATA, Y UNO, H WARD, JM TI ALTERATIONS IN POPULATIONS OF GST-P-IMMUNOREACTIVE SINGLE HEPATOCYTES AND HEPATOCELLULAR FOCI AFTER A SINGLE INJECTION OF N-NITROSODIETHLYAMINE WITH OR WITHOUT PHENOBARBITAL PROMOTION IN MALE F344/NCR RATS SO CANCER LETTERS LA English DT Article DE HEPATOCARCINOGENESIS; GLUTATHIONE S-TRANSFERASE; PLACENTAL FORM; RAT LIVER; IMMUNOHISTOCHEMISTRY; INITIATED HEPATOCYTES ID ENZYME-ALTERED FOCI; CHEMICAL HEPATOCARCINOGENESIS; PRENEOPLASTIC CELLS; HEPATIC FOCI; LIVER; PROLIFERATION; TRANSFERASE; INITIATION; EXPRESSION; APOPTOSIS AB The fate of placental glutathione S-transferase (GST-P)-immunoreactive hepatocytes, detectable in livers of rats soon after treatment with N-nitrosodiethylamine (DEN), was examined sequentially with or without phenobarbital (PB) promotion. Group 1 male F344/NCr rats were administered a single i.p. injection of 200 mg DEN per kg body weight at 5 weeks of age. Group 2 rats were given 500 ppm PB in the diet two weeks after the DEN treatment. Groups of six rats were sequentially sacrificed 16, 42, 70, 126 and 238 days after DEN injection. In DEN-treated rats, GST-P immunoreactive hepatocytes (single cells and multiple cell foci) were detectable 16 days after DEN, the total numbers decreasing by day 70 and thereafter rising again. In the early stages the proportion of single immunoreactive hepatocytes was prominent, but with time a gradual increase in small GST-P+ hepatocellular foci and larger foci became evident. Feeding of PB to rats for 16-238 days after a single DEN injection resulted in increases of both single cells and foci, especially foci composed of more than three hepatocytes. The growth response was increasingly pronounced with time. Adenomas or carcinomas were only observed at 126 or 238 days. Numbers of GST-P+ foci far exceeded the numbers of foci visible in hematoxylin-eosin (H & E) stained sections, and a few H & E foci were negative for GST-P. Many GST-P+ foci smaller than ten cells were composed of histologically normal hepatocytes. Almost all GST-P+ foci identifiable in H&E stained sections were larger than ten cells, consisted of clear cells (in both groups) or mixed (clear-eosinophilc) cells in PB-exposed rats, and appeared to be evenly distributed throughout the three zones of the liver. These results suggest that the promotive effect of PB is most evident as an increase in larger hepatocyte populations composed of more than three GST-P+ hepatocytes, rather than in increasing the populations of single GST-P immunoreactive cells. PB may cause clonal expansion of these single GST-P reactive hepatocytes. This study provides evidence for the hypothesis that some of the GST-P reactive hepatocytes are initiated cells. C1 NCI,FCRDC,INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,PROGRAM RESOURCES,FAIRVIEW 201,FREDERICK,MD 21702. NCI,COMPARAT CARCINOGENESIS LAB,TUMOR PATHOL & PATHOGENESIS SECT,FREDERICK,MD 21701. NCI,VET & TUMOR PATHOL SECT,OFF LAB ANIM SCI,FREDERICK,MD 21701. RI Jang, JaJune/F-6647-2011 FU NCI NIH HHS [N01-CO-74102] NR 25 TC 9 Z9 9 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 JUL 30 PY 1993 VL 71 IS 1-3 BP 89 EP 95 DI 10.1016/0304-3835(93)90102-F PG 7 WC Oncology SC Oncology GA LU536 UT WOS:A1993LU53600015 PM 8364903 ER PT J AU HODGKINSON, CA MOORE, KJ NAKAYAMA, A STEINGRIMSSON, E COPELAND, NG JENKINS, NA ARNHEITER, H AF HODGKINSON, CA MOORE, KJ NAKAYAMA, A STEINGRIMSSON, E COPELAND, NG JENKINS, NA ARNHEITER, H TI MUTATIONS AT THE MOUSE MICROPHTHALMIA LOCUS ARE ASSOCIATED WITH DEFECTS IN A GENE ENCODING A NOVEL BASIC-HELIX-LOOP-HELIX-ZIPPER PROTEIN SO CELL LA English DT Article ID DNA-BINDING; SPLEEN-CELLS; INSERTIONAL MUTATION; WAARDENBURG SYNDROME; MYC ONCOGENE; C-FOS; MICE; DIFFERENTIATION; MOTIF; TRANSCRIPTION AB Mice with mutations at the microphthalmia (mi) locus have some or all of the following defects: loss of pigmentation, reduced eye size, failure of secondary bone resorption, reduced numbers of mast cells, and early onset of deafness. Using a transgenic insertional mutation at this locus, we have identified a gene whose expression is disrupted in transgenic animals. This gene encodes a novel member of the basic-helix-loop-helix-leucine zipper (bHLH-ZIP) protein family of transcription factors, is altered in mice carrying two independent mi alleles (mi and mi(ws)), and is expressed in the developing eye, ear, and skin, all anatomical sites affected by mi. The multiple spontaneous and induced mutations available at mi provide a unique biological resource for studying the role of a bHLH-ZIP protein in mammalian development. C1 NCI,FREDERICK CANC RES & DEV CTR,BASIC RES PROGRAM,ADV BIOSCI LABS,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RP HODGKINSON, CA (reprint author), NINCDS,VIRAL & MOLEC PATHOGENESIS LAB,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CO-74101] NR 63 TC 790 Z9 810 U1 1 U2 22 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUL 30 PY 1993 VL 74 IS 2 BP 395 EP 404 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LP726 UT WOS:A1993LP72600019 PM 8343963 ER PT J AU CALLAHAN, R CROPP, C MERLO, GR DIELLA, F VENESIO, T LIDEREAU, R CAPPA, APM LISICIA, DS AF CALLAHAN, R CROPP, C MERLO, GR DIELLA, F VENESIO, T LIDEREAU, R CAPPA, APM LISICIA, DS TI GENETIC AND MOLECULAR HETEROGENEITY OF BREAST-CANCER CELLS SO CLINICA CHIMICA ACTA LA English DT Article; Proceedings Paper CT 13TH INTERNATIONAL CONF ON BIOCHEMICAL ANALYSIS : CLINICAL IMPACT OF GENOMIC ANALYSIS IN THE DIAGNOSIS AND MANAGEMENT OF GENETIC DISEASE AND CANCER CY MAY 05-06, 1992 CL MUNICH, GERMANY DE BREAST CANCER; MUTATIONS; P53 GENE; NM23 GENE ID TUMOR SUPPRESSOR GENE; MOUSE MAMMARY-TUMORS; TRANSGENIC MICE; PROTO-ONCOGENE; NEU ONCOGENE; PROVIRAL ACTIVATION; PROGNOSTIC FACTORS; TRANSFORMING GENE; GROWTH-FACTORS; INT-2 GENE AB We have undertaken a systematic study of primary human breast tumor DNAs to identify and characterize frequently occurring somatic mutations. Loss of heterozygosity (LOH) was found on chromosomes 1p (37%), 1q (20%), 3p (30%), 7 (41%), 13q (30%), 17p (49%), 17q (29%) and 18q (34%) in our tumor DNA panel. Specific subsets of tumors could be defined based on the particular collection of mutations they contained. One goal of these studies has been to determine whether there is a significant association between specific mutations and clinical parameters of the disease. We have found that LOH on chromosome 17p in tumor DNAs is associated with breast tumors having a high proliferative index and that LOH on chromosome 7 is associated with patients having a poor prognosis. Our analysis of chromosome 17 suggests that there may be as many as four tumor suppressor genes affected in primary human breast tumors. C1 S GIOVANNI HOSP,USL 1,ANAT PATHOL SECT,I-10123 TURIN,ITALY. CTR RENE HUGUENIN,F-92211 ST CLOUD,FRANCE. RP CALLAHAN, R (reprint author), NCI,ONCOGENET SECT,BLDG 10,ROOM 5B50,BETHESDA,MD 20892, USA. NR 81 TC 26 Z9 26 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD JUL 30 PY 1993 VL 217 IS 1 BP 63 EP 73 DI 10.1016/0009-8981(93)90238-Y PG 11 WC Medical Laboratory Technology SC Medical Laboratory Technology GA LW238 UT WOS:A1993LW23800008 PM 8222284 ER PT J AU GEISER, AG BUSAM, KJ KIM, SJ LAFYATIS, R OREILLY, MA WEBBINK, R ROBERTS, AB SPORN, MB AF GEISER, AG BUSAM, KJ KIM, SJ LAFYATIS, R OREILLY, MA WEBBINK, R ROBERTS, AB SPORN, MB TI REGULATION OF THE TRANSFORMING GROWTH-FACTOR-BETA-1 AND FACTOR-BETA-3 PROMOTERS BY TRANSCRIPTION FACTOR SP1 SO GENE LA English DT Article DE CHLORAMPHENICOL ACETYLTRANSFERASE; CAT; GEL SHIFT; SCHNEIDER DROSOPHILA CELLS ID CHLORAMPHENICOL ACETYLTRANSFERASE; DIFFERENTIAL EXPRESSION; SYNERGISTIC ACTIVATION; MAMMALIAN-CELLS; GENE-EXPRESSION; TGF BETA-1; BINDING; MOUSE; INVIVO; DROSOPHILA AB The promoter regions of the genes encoding the three mammalian transforming growth factors-beta (TGF-beta1, -beta2, and -beta3) show little similarity in sequence, suggesting diverse transcriptional control. As a step towards understanding transcriptional regulation of the individual TGF-beta genes we tested each of the three TGF-beta promoter regions (pTGF-beta) for stimulation by the transcription factor Sp1, given that several possible Spl-binding sites were identified by sequence analysis in pTGF-beta1 and pTGF-beta3. A Drosophila melanogaster cell culture system was employed to examine expression levels of pTGF-beta::cat constructs coexpressed with an Sp1 expression plasmid in a cell background devoid of any Sp1 homolog. While both pTGF-beta1 and pTGF-beta3 were strongly stimulated by Sp1, pTGF-beta2 was completely unaffected. Promoter fragments of the TGF-beta1 and TGF-beta3 genes, but not TGF-beta2 were able to compete for binding of Sp1 to DNA oligomers containing consensus Sp1-binding sites. Moreover, specific binding to pTGF-beta1 and pTGF-beta3 fragments was seen using pure Sp1 or nuclear protein extracts. Thus, TGF-beta1 and TGF-beta3 (but not TGF-beta2) are regulated by the transcription factor Sp1, indicating differential transcriptional regulation of genes whose protein products are functionally very similar. RP GEISER, AG (reprint author), NCI,CHEMOPREVENT LAB,BLDG 41,ROOM C629,BETHESDA,MD 20892, USA. NR 29 TC 71 Z9 75 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 JUL 30 PY 1993 VL 129 IS 2 BP 223 EP 228 DI 10.1016/0378-1119(93)90272-5 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA LP104 UT WOS:A1993LP10400009 PM 8325508 ER PT J AU TAYLOR, JA BELL, DA NAGORNEY, D AF TAYLOR, JA BELL, DA NAGORNEY, D TI L-MYC PROTOONCOGENE ALLELES AND SUSCEPTIBILITY TO HEPATOCELLULAR-CARCINOMA SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID FRAGMENT-LENGTH-POLYMORPHISM; LUNG-CANCER PATIENTS; BREAST-CANCER; GENE; METASTASIS; EXPRESSION AB A common inherited RFLP of the L-myc proto-oncogene has been reported to correlate with cancer susceptibility or prognosis for some tumors. Using a PCR-based RFLP assay on DNA extracted from peripheral blood samples, we determined the L-myc EcoRI genotype of patients with HCC, patients with other liver tumors, and healthy controls. In this polymorphism there are 2 alleles, L and S, which define 3 possible genotypes: LL, LS, and SS. While the genotype distribution of patients with other liver tumors and healthy controls do not differ from one another, both differ significantly from the genotype distribution of patients with HCC. This difference is primarily the result of a low frequency of the SS genotype among HCC patients compared to controls or other liver tumor patients. Persons with the SS genotype appear to be protected against HCC and have roughly one-ninth the risk of persons who carry one or more copies of the L allele. Within HCC cases, patients with different L-myc genotypes show slight, but not statistically significant, differences in tumor characteristics and survival. (C) 1993 Wiley-Liss, Inc. C1 NIEHS,BIOCHEM RISK ANAL LAB,RES TRIANGLE PK,NC 27709. MAYO CLIN & MAYO FDN,DEPT SURG,ROCHESTER,MN 55905. RP TAYLOR, JA (reprint author), NIEHS,EPIDEMIOL BRANCH,MD A3-05,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI taylor, jack/0000-0001-5303-6398 NR 18 TC 29 Z9 29 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 30 PY 1993 VL 54 IS 6 BP 927 EP 930 DI 10.1002/ijc.2910540610 PG 4 WC Oncology SC Oncology GA LQ457 UT WOS:A1993LQ45700009 PM 8392982 ER PT J AU CIARDIELLO, F BIANCO, C NORMANNO, N BALDASSARRE, G PEPE, S TORTORA, G BIANCO, AR SALOMON, DS AF CIARDIELLO, F BIANCO, C NORMANNO, N BALDASSARRE, G PEPE, S TORTORA, G BIANCO, AR SALOMON, DS TI INFECTION WITH A TRANSFORMING GROWTH-FACTOR-ALPHA ANTISENSE RETROVIRAL EXPRESSION VECTOR REDUCES THE IN-VITRO GROWTH AND TRANSFORMATION OF A HUMAN COLON-CANCER CELL-LINE SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID MAMMARY EPITHELIAL-CELLS; HA-RAS PROTOONCOGENE; FACTOR MESSENGER-RNA; TGF-ALPHA; TRANSGENIC MICE; ANTISENSE RNA; COLORECTAL TUMORS; CARCINOMA; OLIGODEOXYNUCLEOTIDES; OVEREXPRESSION AB Transforming growth factor a (TGFalpha) is a growth factor produced by colon cancer cells which may function as an autocrine growth regulator. Therefore, the proliferation and transformation of colon cancer cells might be attenuated by blocking the production of endogenous TGFalpha. GEO cells, from a human colon carcinoma cell line that expresses TGFalpha and functional epidermal growth factor (EGF) receptors, were infected with a replication-defective, recombinant amphotropic retroviral expression vector containing the neomycin-resistance gene and a 435-bp ApaI-EcoRI coding fragment of the human TGF alpha cDNA oriented in the 3' to 5' direction under the transcriptional control of the heavy-metal-inducible mouse metallothionein I promoter. Following antibiotic selection, G418-resistant colonies were pooled and expanded into a cell line (GEO TGFalpha AS cells). A 50 to 70% inhibition in the production of secreted and cell-associated TGFalpha protein was observed in GEO TGFalpha AS cells that had been maintained in CdCl2-supplemented medium. Moreover, a growth inhibition of 70% and SO% was observed in CdCl2-treated GEO TGFalpha AS cells under anchorage-dependent and anchorage-independent culture conditions, respectively. In contrast, CdCl2 treatment of parental GEO cells had no significant effect upon these parameters. Our results suggest that TGFalpha may be involved in modulating the in vitro cell growth and transformation of human colon cancer cells that express both this growth factor and its cognate receptor. (C) 1993 Wiley-Liss, Inc. C1 NCI,TUMOR IMMUNOL & BIOL LAB,TUMOR GROWTH FACTOR SECT,BETHESDA,MD 20892. RP CIARDIELLO, F (reprint author), UNIV NAPLES,DIV MED & CHIRURG 2,CATTEDRA ONCOL MED,VIA S PANSINI S,I-80131 NAPLES,ITALY. RI Baldassarre, Gustavo/K-1350-2016 OI Baldassarre, Gustavo/0000-0002-9750-8825 NR 49 TC 36 Z9 36 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 30 PY 1993 VL 54 IS 6 BP 952 EP 958 DI 10.1002/ijc.2910540615 PG 7 WC Oncology SC Oncology GA LQ457 UT WOS:A1993LQ45700014 PM 8335403 ER PT J AU DEVITA, VT HUBBARD, SM AF DEVITA, VT HUBBARD, SM TI HODGKINS-DISEASE - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID CHEMOTHERAPY C1 NCI,BETHESDA,MD 20892. RP DEVITA, VT (reprint author), MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 29 PY 1993 VL 329 IS 5 BP 361 EP 362 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA LN621 UT WOS:A1993LN62100024 ER PT J AU MURAMATSU, T KINCAID, RL AF MURAMATSU, T KINCAID, RL TI MOLECULAR-CLONING OF A FULL-LENGTH CDNA-ENCODING THE CATALYTIC SUBUNIT OF HUMAN CALMODULIN-DEPENDENT PROTEIN PHOSPHATASE (CALCINEURIN-A-ALPHA) SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Note DE CALCINEURIN; CDNA SEQUENCE; AMINO ACID SEQUENCE; (HUMAN) ID CYCLOSPORINE-A; IDENTIFICATION; DOMAIN; ACTIVATION; PROMOTER; ISOFORMS; FK-506; TESTIS; CELLS; BRAIN AB A complementary DNA for human calcineurin Aalpha (protein phosphatase-2B), encoding a protein of 521 amino acids, was isolated from a hippocampus library. The deduced human sequence differs from that of mouse in only two amino acids, demonstrating that the structure of this catalytic subunit has been strictly conserved during mammalian evolution. Such high homology is in contrast to that seen for calcineurin Agamma, an isoform that shows only 88% identity between human and mouse (Muramatsu, T. and Kincaid, R.L. (1992) Biochem. Biophys. Res. Commun. 188, 265-271). C1 NIAAA, MOLEC & CELLULAR NEUROBIOL LAB, IMMUNOL SECT, 12501 WASHINGTON AVE, ROCKVILLE, MD 20852 USA. NR 22 TC 27 Z9 28 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 JI Biochim. Biophys. Acta PD JUL 28 PY 1993 VL 1178 IS 1 BP 117 EP 120 DI 10.1016/0167-4889(93)90117-8 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LQ172 UT WOS:A1993LQ17200014 PM 8392375 ER PT J AU DECOSTERD, LA PARSONS, IC GUSTAFSON, KR CARDELLINA, JH MCMAHON, JB CRAGG, GM MURATA, Y PANNELL, LK STEINER, JR CLARDY, J BOYD, MR AF DECOSTERD, LA PARSONS, IC GUSTAFSON, KR CARDELLINA, JH MCMAHON, JB CRAGG, GM MURATA, Y PANNELL, LK STEINER, JR CLARDY, J BOYD, MR TI HIV INHIBITORY NATURAL-PRODUCTS .11. STRUCTURE, ABSOLUTE STEREOCHEMISTRY, AND SYNTHESIS OF CONOCURVONE, A POTENT, NOVEL HIV-INHIBITORY NAPHTHOQUINONE TRIMER FROM A CONOSPERMUM SP SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article AB Bioassay-guided fractionation provided conocurvone (1), a novel trimeric naphthoquinone derivative, as the active anti-HIV constituent of an extract from a Conospermum sp. The related naphthoquinone monomer teretifolione B (2) also was isolated from a Conospermum sp. extract. The absolute stereochemistry of 2 was established by X-ray crystallographic analysis of the p-bromobenzoate derivative 6. Base-catalyzed coupling of 2 equiv of teretifolione B (2) with the deoxy derivative 8 provided compound 1, which was identical in all respects with the natural product. While compound 2 was inactive against HIV, the natural and synthetic conocurvone (1) and the synthetic trimeric analog 4 were all active and equipotent, preventing the cytopathic effects and replication of HIV in human T-lymphoblastic cells (CEM-SS) over a concentration range of 0.02-50 muM. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,DRUG DISCOVERY RES & DEV LAB,BLDG 1052,ROOM 121,FREDERICK,MD 21702. NR 14 TC 58 Z9 59 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUL 28 PY 1993 VL 115 IS 15 BP 6673 EP 6679 DI 10.1021/ja00068a026 PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA LT673 UT WOS:A1993LT67300026 ER PT J AU UENG, TH UENG, YF TSAI, JN CHAO, IC CHEN, TL PARK, SS IWASAKI, M GUENGERICH, FP AF UENG, TH UENG, YF TSAI, JN CHAO, IC CHEN, TL PARK, SS IWASAKI, M GUENGERICH, FP TI INDUCTION AND INHIBITION OF CYTOCHROME P-450-DEPENDENT MONOOXYGENASES IN HAMSTER TISSUES BY ETHANOL SO TOXICOLOGY LA English DT Article DE ETHANOL; CYTOCHROME-P-450; MONOOXYGENASE; INDUCTION; INHIBITION; HAMSTER ID INDUCIBLE CYTOCHROME-P-450; MONOCLONAL-ANTIBODIES; LIVER-MICROSOMES; CROSS-REACTIVITY; RAT-LIVER; PURIFICATION; METABOLISM; ENZYMES; MECHANISMS; CHEMICALS AB The effects of ethanol on hamster hepatic and extrahepatic monooxygenases were determined in the present study. Chronic ethanol administration increased cytochrome P-450 (P-450) content and monooxygenase activities towards aniline, N-nitrosodimethylamine, and 7-ethoxyresorufin. In contrast, benzphetamine and benzo(a)pyrene oxidation rates were decreased 21-24% by ethanol. In kidney, ethanol pretreatment increased P-450 content, aniline and N-nitrosodimethylamine oxidation activities. In lung, ethanol ingestion selectively increased aniline hydroxylation without affecting other monooxygenase activities. Intestinal monooxygenase activity was refractory to ethanol induction. Immunoblotting of the microsomal proteins showed that ethanol induced a protein cross-reactive with rabbit antibody raised against human P-450 2E1 in hamster liver, kidney, and lung. Immunoblotting analysis using mouse monoclonal antibody 1-12-3 raised against scup P-450 1A1 revealed that ethanol induced an immunorelated protein in hamster liver, kidney, and lung. Induction of P-450 2E1 and 1A was not observed with intestinal protein blots. Immunoblotting analysis using mouse monoclonal antibody 2-66-3 against rat P-450 2B1 showed inhibition of an immunorelated protein in ethanol-treated hamster liver. The inhibitory effect on P-450 2B was not observed with extrahepatic tissues. These results suggest that ethanol has the ability to induce P-450s 2E1 and 1A and to inhibit P-450 2B in hamster tissues. C1 NCI,FCRDC,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. VANDERBILT UNIV,MED CTR,SCH MED,DEPT BIOCHEM,NASHVILLE,TN 37232. VANDERBILT UNIV,MED CTR,SCH MED,CTR MOLEC TOXICOL,NASHVILLE,TN 37232. RP UENG, TH (reprint author), NATL TAIWAN UNIV,COLL MED,INST TOXICOL,1 JEN AI RD,SECT 1,TAIPEI,TAIWAN. FU NCI NIH HHS [CA44353]; NIEHS NIH HHS [ES00267] NR 31 TC 22 Z9 22 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD JUL 28 PY 1993 VL 81 IS 2 BP 145 EP 154 DI 10.1016/0300-483X(93)90006-E PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA LW294 UT WOS:A1993LW29400006 PM 8378940 ER PT J AU MCPHIE, P PARKISON, C LEE, BK CHENG, SY AF MCPHIE, P PARKISON, C LEE, BK CHENG, SY TI STRUCTURE OF THE HORMONE-BINDING DOMAIN OF HUMAN BETA-1 THYROID-HORMONE NUCLEAR RECEPTOR - IS IT AN ALPHA-BETA BARREL SO BIOCHEMISTRY LA English DT Article ID RETINOIC ACID RECEPTORS; SECONDARY STRUCTURE; PYRUVATE-KINASE; RXR-BETA; PROTEIN; PREDICTION; GENE; SUPERFAMILY; RESISTANCE; ENZYMES AB To understand the structure of the hormone binding domain (HBD) of human beta1 thyroid hormone nuclear receptor (h-TRbeta1), truncated h-TRbeta1 fragments, MD32 (M169-D456), KD29 (K201-D456), DD28 (D211-D456), KD25 (K235-D456), and KP28 (K201-P448), were analyzed by circular dichorism (CD). MD32 and KD29 show intense CD spectra with double minima at 222 and 208-210 nm, indicating the presence of extensive regions of alpha-helix. DD28 and KD25 have spectra which are reduced in intensity with minima around 215 nm, characteristic of a beta-sheet. The observed spectra are compatible with sequence analysis which predicts that HBD contains alternating stretches of alpha-helix and beta-strand. These extensive decreases in secondary structure in DD28 and KP28 in which the predicted first beta-strand or last alpha-helix was deleted, respectively, were accompanied by the loss of hormone binding activity. On the basis of these results, we suggest a new model for h-TRbeta1 consisting of the known DNA binding domain linked by an alpha-helical hinge to the HBD, with the tertiary structure of an alpha/beta barrel. The model is compatible with previous chemical and genetic studies on the structure of this protein. C1 NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892. NR 37 TC 15 Z9 15 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 JUL 27 PY 1993 VL 32 IS 29 BP 7460 EP 7465 DI 10.1021/bi00080a017 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LP643 UT WOS:A1993LP64300017 PM 8338844 ER PT J AU KUMAR, A KIM, HR SOBOL, RW BECERRA, SP LEE, BJ HATFIELD, DL SUHADOLNIK, RJ WILSON, SH AF KUMAR, A KIM, HR SOBOL, RW BECERRA, SP LEE, BJ HATFIELD, DL SUHADOLNIK, RJ WILSON, SH TI MAPPING OF NUCLEIC-ACID BINDING IN PROTEOLYTIC DOMAINS OF HIV-1 REVERSE-TRANSCRIPTASE SO BIOCHEMISTRY LA English DT Article ID ROUS-SARCOMA VIRUS; RNASE-H; NUCLEOTIDE-SEQUENCE; PRIMER BINDING; PROTEINS; SITE; IDENTIFICATION; PROCESSIVITY; RESISTANCE; MUTATIONS AB Human immunodeficiency virus type-1 (HIV-1) reverse transcriptase (RT) and its domain fragments were used to map nucleic acid binding sites within the enzyme. Discrete domain fragments were produced after the digestion of three forms of RT (p66, p66/p51 heterodimer, and p51) with V8 protease or trypsin, and the primary structure of each domain fragment was mapped by both immunoblotting and N-terminal amino acid sequence analysis. These domain fragments represent N-terminal, middle, or C-terminal regions of RT. Using Northwestern or Southwestern blotting assays, the domain fragments were evaluated for nucleic acid binding. In this technique, RT proteins are electroblotted onto the membrane and renatured after SDS-PAGE; the proteins are then probed with the primer analogues P-32-labeled d(T)16 or P-32-labeled tRNA(Lys,3). A V8 protease domain fragment spanning residues 195 to approximately 300 (p12), which was found earlier to be UV cross-linked to the primer in intact RT [Sobol et al. (1991) Biochemistry 30, 10623-10631], showed binding to both nucleic acid probes. We first localized nucleic acid binding in p66 to an N-terminal domain fragment of residues 1 congruent-to 300. By contrast, a C-terminal domain fragment termed p30(303 congruent-to 560) did not show nucleic acid binding. To investigate the role of the region just N-terminal to residue 303, an expression vector named pRC-35 encoding residues 273-560 was constructed. We purified the corresponding expressed protein, p35, and found that this protein binds to tRNA(Lys,3), demonstrating that residues 273-302 are able to confer nucleic acid binding to the binding-negative C-terminal segment spanning residues 303 congruent-to 560. Further, an additional domain fragment corresponding to residues 1 congruent-to 230 (p29) was found to have nucleic acid-binding capacity. These results indicate that RT nucleic acid binding occurs in at least two domains in the N-terminal half of p66. The results appear in good agreement with the model of template-primer bound to the p66/p51 heterodimer, proposed by Kohlstaedt et al. [(1992) Science 256, 1780-1789]. C1 NCI,BIOCHEM & EXPTL CARCINOGENESIS LABS,BETHESDA,MD 20892. TEMPLE UNIV,HLTH SCI CTR,SCH MED,DEPT BIOCHEM,PHILADELPHIA,PA 19140. RP KUMAR, A (reprint author), UNIV TEXAS,SEALY CTR MOLEC SCI,MED BRANCH,GALVESTON,TX 77555, USA. RI Sobol, Robert/E-4125-2013 OI Sobol, Robert/0000-0001-7385-3563 NR 36 TC 15 Z9 15 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 JUL 27 PY 1993 VL 32 IS 29 BP 7466 EP 7474 DI 10.1021/bi00080a018 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LP643 UT WOS:A1993LP64300018 PM 7687875 ER PT J AU THOMAS, DL FACTOR, SH KELEN, GD WASHINGTON, AS TAYLOR, E QUINN, TC AF THOMAS, DL FACTOR, SH KELEN, GD WASHINGTON, AS TAYLOR, E QUINN, TC TI VIRAL-HEPATITIS IN HEALTH-CARE PERSONNEL AT THE JOHNS-HOPKINS-HOSPITAL - THE SEROPREVALENCE OF AND RISK-FACTORS FOR HEPATITIS-B VIRUS AND HEPATITIS-C VIRUS-INFECTION SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID NON-A-HEPATITIS; BORNE NON-A; UNITED-STATES; POSTTRANSFUSION HEPATITIS; OCCUPATIONAL EXPOSURES; NEEDLESTICK INJURY; HOMOSEXUAL MEN; E-ANTIGEN; ANTIBODIES; BLOOD AB Background: Health care personnel are at increased risk of occupational acquisition of hepatitis B virus (HBV) infection. While effective vaccination for HBV is widely available, the prevalence of HBV and vaccine acceptance in hospital personnel have not been recently assessed. In addition, hepatitis C virus (HCV) is a newly recognized cause of parenterally acquired hepatitis, and the risk of HCV transmission to health care personnel remains unclear. Methods: From April to December 1991, health care personnel at The Johns Hopkins Hospital, Baltimore, Md, were offered anonymous testing for HBV and HCV and were asked to complete a confidential questionnaire. Serum samples were tested for HBV surface antigen and antibodies to HBV core antigen, HBV surface antigen, and HCV. Seroprevalence rates were compared with those detected in local blood donors during the same year. Results: Antibodies to HBV core antigen were found in 59 (6.2%) of 943 health care workers compared with 1879 (1.8%) of 104 239 local blood donors (P<.001). In contrast, antibodies to HCV were found in seven (0.7%) of 943 health care workers and 0.4% of local blood donors (P=.10). Infection with HBV was associated with age (greater-than-or-equal-to 33 years) (P<.001), black race (P<.001), type of health care worker (nurse) (P=.02), 10 or more years of clinical employment (P=.003), and lack of HBV vaccination (P<.001). After logistic regression, only absence of HBV vaccination was independently associated with HBV infection (P<.001). Conclusion: These data suggest that the prevalence of HCV infection in health care personnel at The Johns Hopkins Hospital is similar to that observed in local blood donors, and that HBV may be more efficiently transmitted than HCV in the health care setting. Efforts to vaccinate health care personnel against HBV should be vigorously pursued since 23% remain unvaccinated after 9 years of HBV vaccine availability. C1 JOHNS HOPKINS UNIV HOSP,1159 RICHARD STARR ROSS BLDG,720 RUTLAND AVE,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DIV INFECT DIS,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DIV EMERGENCY MED,BALTIMORE,MD 21205. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RI Quinn, Thomas/A-2494-2010; OI Kelen, Gabor/0000-0002-3236-8286 NR 51 TC 94 Z9 97 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 26 PY 1993 VL 153 IS 14 BP 1705 EP 1712 DI 10.1001/archinte.153.14.1705 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA LP299 UT WOS:A1993LP29900009 PM 8333808 ER PT J AU HERMOUET, S MURAKAMI, T SPIEGEL, AM AF HERMOUET, S MURAKAMI, T SPIEGEL, AM TI STABLE CHANGES IN EXPRESSION OR ACTIVATION OF G-PROTEIN ALPHA-I OR ALPHA-Q SUBUNITS AFFECT THE EXPRESSION OF BOTH BETA-1 AND BETA-2 SUBUNITS SO FEBS LETTERS LA English DT Article DE G-PROTEIN; ALPHA-SUBUNIT AND BETA-SUBUNIT; PROTEIN EXPRESSION; MESSENGER RNA EXPRESSION ID GTP-BINDING PROTEIN; NIH 3T3 CELLS; GAMMA-SUBUNITS; ADENYLYL CYCLASE; 3RD FORM; THYROID-HORMONES; PHOSPHOLIPASE-C; ANTIBODIES; RECEPTOR; IDENTIFICATION AB G proteins consist of three subunits: alpha, beta and gamma. Four beta subunits have been cloned: beta1 and beta4 (36 kDa), and beta2 and beta3 (35 kDa). We studied endogenous beta subunits in mouse NIH 3T3 fibroblasts stably expressing high levels of G protein alpha subunits after transfection with cDNAs encoding alpha(il), alpha(i2), alpha(i3) and alpha(q). Immunoblots showed that NIH 3T3 cells express beta36 and beta35 subunits; in these cells, beta35 subunits are four times more abundant than beta36 subunits. We could detect beta1 and beta2 mRNA, but neither beta3 nor beta4 mRNA. We found that a stable increase in expression of wild-type alpha(il), alpha(i2), alpha(i3) or alpha(q) subunits is always accompanied by an increase in beta1 and beta2 MRNA and protein levels. There was no evidence of selectivity for an increase in beta1 rather than beta2 subunits depending on the type of alpha subunit overexpressed. However, constitutive activation or inactivation of alpha subunits induced specific changes in beta subunits. Expression of constitutively inactivated alpha(i2) subunits was accompanied by an increase in mRNA and protein levels of both beta subunits. In contrast, cells expressing constitutively activated alpha(i2) subunits did not show any change in the amount of beta proteins expressed in membranes, despite a significant increase in beta1 and beta2 mRNA. We conclude that stable changes in the levels of expression or degree of activation of Galpha subunits affect the level of expression, and possibly the turn-over, of beta subunits, without selectivity among beta1 and beta2 subunits. RP HERMOUET, S (reprint author), NIDDKD,MOLEC PATHOPHYSIOL BRANCH,BLDG 10,ROOM 8C101,BETHESDA,MD 20892, USA. NR 55 TC 18 Z9 18 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 JUL 26 PY 1993 VL 327 IS 2 BP 183 EP 188 DI 10.1016/0014-5793(93)80166-R PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA LN694 UT WOS:A1993LN69400012 PM 8335108 ER PT J AU KHILKO, SN CORR, M BOYD, LF LEES, A INMAN, JK MARGULIES, DH AF KHILKO, SN CORR, M BOYD, LF LEES, A INMAN, JK MARGULIES, DH TI DIRECT-DETECTION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I BINDING TO ANTIGENIC PEPTIDES USING SURFACE-PLASMON RESONANCE - PEPTIDE IMMOBILIZATION AND CHARACTERIZATION OF BINDING-SPECIFICITY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BIOSPECIFIC INTERACTION ANALYSIS; T-CELL RECEPTOR; BETA-2-MICROGLOBULIN TRANSLATED INVITRO; HLA-B27 HEAVY-CHAIN; HL-A ANTIGENS; MHC MOLECULE; VIRAL PEPTIDES; MONOCLONAL-ANTIBODY; ENVELOPE PROTEIN; SMALL SUBUNIT AB We have developed model systems in which the binding of purified, genetically engineered, soluble analogues of major histocompatibility complex (MHC) class I molecules to immobilized antigenic peptides can be monitored in real time using surface plasmon resonance (SPR). Synthetic analogues of several peptides known to bind different mouse and human MHC class I molecules were prepared with cysteine residues substituted at appropriate positions. The analogue peptides were immobilized via the bifunctional reagent N-gamma-maleimidobutyryloxy-succinimide to amino groups generated on the dextran-modified gold surface of a biosensor flow cell. Using this approach, each position in the sequence of an H-2L(d)-specific viral peptide, pMCMV (YPHFMPTNL), was used for coupling, and the resulting surfaces were tested for binding of the soluble analogue of H-2L(d), H-2L(d)s. In accord with our previously described H-2L(d)/pMCMV three-dimensional structural model, only those residues of the peptide that remain exposed following binding (positions 4-8) can be replaced by cysteine and used for coupling. Stable binding of soluble MHC class I molecules, H-2L(d)s, H-2D(d)s, H-2K(b)s, and HLA-A2(s) to their respective immobilized cognate peptides was detected by SPR. Specificity of the peptide/MHC interaction was characterized both by direct binding using immobilized peptides and by competition with peptides in solution, and in general was consistent with known immunological reactivity. Some peptides bound not only their cognate MHC molecule, but others at lower apparent affinity. Measurement of real time binding of MHC class I molecules to peptides immobilized through specific side chains suggests the application of a similar approach to the study of the interaction of peptides with a wide variety of peptide-binding macromolecules. C1 NIAID,BIOORGAN CHEM SECT,IMMUNOL LAB,BLDG 10,RM 11N311,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NIAID,MOLEC BIOL SECT,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT MED,BETHESDA,MD 20814. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 76 TC 65 Z9 65 U1 1 U2 8 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 JUL 25 PY 1993 VL 268 IS 21 BP 15425 EP 15434 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LN305 UT WOS:A1993LN30500020 PM 8393442 ER PT J AU YOSHIMURA, T YUHKI, N WANG, MH SKEEL, A LEONARD, EJ AF YOSHIMURA, T YUHKI, N WANG, MH SKEEL, A LEONARD, EJ TI CLONING, SEQUENCING, AND EXPRESSION OF HUMAN MACROPHAGE STIMULATING PROTEIN (MSP, MST1) CONFIRMS MSP AS A MEMBER OF THE FAMILY OF KRINGLE PROTEINS AND LOCATES THE MSP GENE ON CHROMOSOME-3 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; CELL CARCINOMA; SHORT ARM; LOCUS AB A human hepatoma (HepG2) cell line library was screened with an oligonucleotide probe for macrophage stimulating protein (MSP) to clone an MSP cDNA. Deduced sequences of isolated clones were compared with peptide fragment sequences of MSP. MSP9 cDNA encoded most of the known sequence of MSP except for a small segment of the 5' end of the open reading frame. Consequently, a hybrid 2300-base pair cDNA that encoded the complete MSP amino acid sequence was constructed from 2 clones. Culture fluid from COS-7 cells transfected with this full-length MSP cDNA had MSP biological activity, and the expressed MSP was detected by immunoprecipitation with antibody against native MSP. The deduced amino acid sequence of MSP includes 4 kringle domains, which have been found in hepatocyte growth factor and several proteins of the blood coagulation system. Among them, MSP has the highest sequence similarity to hepatocyte growth factor (45% identity). The MSP cDNA hybridized strongly to mRNA from liver, and to a lesser extent to mRNA from kidney and pancreas, suggesting that a cell type in the liver is the source of MSP. Several cloned and sequenced MSP cDNAs had insertions or deletions, suggesting that alternatively spliced MSP mRNAs may occur. This was reflected in Northern blots probed with an MSP cDNA, which showed more than one mRNA species. Furthermore, although the gene coding for MSP is on chromosome 3, the sequence of one of the cDNAs was identical with a unique sequence in chromosome 1, indicating that there may be a family of MSP genes, located on chromosomes 3 and 1. C1 NCI,FREDERICK CANC RES & DEV CTR,GENET SECT,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. RP YOSHIMURA, T (reprint author), NCI,FREDERICK CANC RES & DEV CTR,IMMUNOPATHOL SECT,IMMUNOBIOL LAB,BLDG 560,RM 12-46,FREDERICK,MD 21702, USA. NR 20 TC 157 Z9 160 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 JUL 25 PY 1993 VL 268 IS 21 BP 15461 EP 15468 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LN305 UT WOS:A1993LN30500024 PM 8393443 ER PT J AU BOSSER, R ALIGUE, R GUERINI, D AGELL, N CARAFOLI, E BACHS, O AF BOSSER, R ALIGUE, R GUERINI, D AGELL, N CARAFOLI, E BACHS, O TI CALMODULIN CAN MODULATE PROTEIN-PHOSPHORYLATION IN RAT-LIVER CELLS NUCLEI SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CASEIN KINASE-II; PROLACTIN GENE-EXPRESSION; BINDING PROTEINS; GROWTH-FACTOR; IDENTIFICATION; MATRIX; LOCALIZATION; REGENERATION; ASSOCIATION; ACTIVATION AB This report describes the immunological identification of a 60-kDa calmodulin-binding protein, previously detected in the nuclei of rat liver cells (Bachs, O., Lanini, L., Serratosa, J., Coll, M. J., Bastos, R., Aligue, R., Rius, E., and Carafoli, E. (1990) J. Biol. Chem. 265, 18595-18600), as the calmodulin-dependent protein phosphatase calcineurin. Calcineurin could be extracted from the nuclei by incubation with DNase and RNase, indicating that it is associated with nuclear structures sensitive to the action of nucleases (chromatin or/and ribonucleoproteins). The presence of calcineurin in the nuclei of rat liver cells indicates that calmodulin may modulate the phosphorylation level of nuclear proteins by promoting their dephosphorylation. This report also shows that calmodulin inhibits the activity of casein kinase-2 in the nuclear fractions obtained by nuclease extraction. Phosphorylation experiments indicate that casein kinase-2 phosphorylates three major substrates of 100, 42-44, and 37 kDa as well as other minor proteins in the nuclease extracts. Calmodulin reduces the phosphorylation level of the two latter major proteins and of a minor band of 50 kDa. Thus, nuclear calmodulin in rat liver cells could regulate phosphorylation of nuclear proteins by at least two mechanisms: 1) activation of calcineurin and 2) inhibition of casein kinase-2. C1 UNIV BARCELONA,FAC MED,DEPT CELL BIOL,CASANOVA 143,E-08036 BARCELONA,SPAIN. SWISS FED INST TECHNOL,INST BIOCHEM,CH-8092 ZURICH,SWITZERLAND. NCI,BIOCHEM LAB,BETHESDA,MD 20892. RI Agell, Neus/E-9640-2016; Carafoli, Ernesto/K-5192-2016 OI Carafoli, Ernesto/0000-0002-7826-0094 NR 56 TC 39 Z9 39 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 JUL 25 PY 1993 VL 268 IS 21 BP 15477 EP 15483 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LN305 UT WOS:A1993LN30500026 PM 8393444 ER EF